.I 125536 .U 89315773 .S Proc Natl Acad Sci U S A 8910; 86(14):5242-6 .M Amino Acid Sequence; Animal; Argipressin/GE; Base Sequence; Cloning, Molecular/*; Comparative Study; DNA/*GE; DNA Polymerases; Fishes/*GE; Gene Amplification; Genes, Structural; Human; Molecular Sequence Data; Oxytocin/*AA/GE; Protein Precursors/*GE; Sequence Homology, Nucleic Acid; Support, Non-U.S. Gov't; Vasotocin/*GE. .T Vasotocin and isotocin precursors from the white sucker, Catostomus commersoni: cloning and sequence analysis of the cDNAs. .P JOURNAL ARTICLE. .W The nucleotide sequences of cloned cDNAs encoding the precursors for vasotocin and isotocin have been elucidated by analyzing a lambda gt11 library constructed from poly(A)+ RNA from the hypothalamic region of the teleost fish Catostomus commersoni. Screening of the library was carried out with synthetic oligonucleotide probes deduced from the amino acid sequences of the nonapeptides vasotocin and isotocin. The cDNA nucleotide sequences predict isotocin and vasotocin prohormone precursors each consisting of a signal peptide, a hormone moiety, and a neurophysin-like molecule. However, in comparison to their mammalian counterparts, both fish neurophysins are extended at their C termini by an approximately 30 amino acid sequence with a leucine-rich core segment. These extensions show striking similarities with the glycopeptide moiety (the so-called copeptin) present in mammalian vasopressin precursors, except that they lack the consensus sequence for N-glycosylation. These data suggest that mammalian copeptin is derived from the C terminus of an ancestral neurophysin. .A Heierhorst J; Morley SD; Figueroa J; Krentler C; Lederis K; Richter D. .I 125537 .U 89315780 .S Proc Natl Acad Sci U S A 8910; 86(14):5276-80 .M Amino Acid Sequence; Animal; Base Sequence; Blotting, Northern; Cloning, Molecular; DNA/*GE/IP; Gene Amplification/*; Genes, Structural/*; Golgi Apparatus/*EN; Liver/*EN; Mannosidases/*GE; Molecular Sequence Data; Oligonucleotide Probes; Rats; RNA, Messenger/GE; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Transcription, Genetic. .T Isolation of a rat liver Golgi mannosidase II clone by mixed oligonucleotide-primed amplification of cDNA. .P JOURNAL ARTICLE. .W A clone encoding Golgi mannosidase II (MII; GlcNAc-transferase I-dependent alpha 1,3(alpha 1,6) mannosidase), an enzyme involved in asparagine-linked oligosaccharide processing, was isolated from a rat liver lambda gt11 cDNA library by a method that employs a modification of the polymerase chain reaction. Specific oligonucleotide primers were designed from two regions of protein sequence and were combined in an amplification reaction with a single-stranded cDNA preparation derived from rat liver poly(A)+ RNA. Based upon mapping of the protein sequences 42 kDa apart on the MII polypeptide, the procedure was expected to generate an approximately 1150-base-pair amplification product representing a segment of the MII gene between the two primer regions. The size of the amplified product (1170 base pairs) was in close agreement with this predicted fragment size. The authenticity of the amplified fragment was confirmed by the agreement of the DNA sequence with additional protein sequence data. A 1474-base-pair clone was isolated from a cDNA library by plaque hybridization using the amplification fragment as a radiolabeled probe. The nucleotide sequence of this clone predicts a single continuous open reading frame and, based upon a polypeptide molecular mass of 117 kDa for the enzyme subunit, is consistent with the clone representing approximately 50% of the coding sequence of MII. Both the clone and the amplification product hybridized to a rat liver mRNA of approximately 8 kilobases, a message size approximately 4.7 kilobases larger than the size of the predicted open reading frame. This extensive non-coding information on the MII message is a feature common to two other Golgi processing enzymes, both of which contain most of the non-coding information on the 3' end of their messages. The function of these disproportionately large untranslated regions is not clear. .A Moremen KW. .I 125538 .U 89315782 .S Proc Natl Acad Sci U S A 8910; 86(14):5286-90 .M Alanine/*; Amino Acid Sequence; Circular Dichroism; Kinetics; Peptides/*/CS; Protein Conformation/*; Structure-Activity Relationship; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Thermodynamics. .T Unusually stable helix formation in short alanine-based peptides. .P JOURNAL ARTICLE. .W Short, 16-residue, alanine-based peptides show stable alpha-helix formation in H2O. This result is surprising when contrasted with the classical view that regards the alpha-helix as a marginally stable structure in H2O and considers short helices unstable. The alanine-based peptides are solubilized by insertion of three or more residues of a single charge type, lysine (+) or glutamic acid (-). The results cannot be explained by helix stabilization resulting from concentration-dependent association or by the interaction of charged residues with the helix dipole. Our results are not predicted by the parameters for alanine and lysine that have been determined by the "host-guest" method: these parameters predict that a 16-residue peptide should not show measurable alpha-helix formation. Analysis of the role of the hydrophobic interaction in alpha-helix formation [Richards, F.M. & Richmond, T. (1978) in Molecular Interactions and Activity in Proteins, Ciba Foundation Symposium 60, ed. Wolstenholme, G.E. (Excepta Medica Amsterdam), pp. 23-25] does not show an unusually strong hydrophobic interaction in a helical block of alanine residues. The likely explanation for our results is, therefore, that individual alanine residues have a high helical potential. It is not yet known whether any other amino acids show this property, and the origin of this property is also unknown. .A Marqusee S; Robbins VH; Baldwin RL. .I 125539 .U 89315783 .S Proc Natl Acad Sci U S A 8910; 86(14):5291-5 .M Amino Acid Sequence; Animal; Avian Leukosis Viruses/*GE; Base Sequence; Cloning, Molecular; Comparative Study; Erythroblastosis Virus, Avian/EN/*GE; Fibroblasts; Genes, Reiterated/*; Genes, Structural; Molecular Sequence Data; Oncogene Proteins, Viral/*GE; Oncogenes/*; Protein-Tyrosine Kinase/*GE; Rats; Restriction Mapping; Sequence Homology, Nucleic Acid; Support, U.S. Gov't, P.H.S.. .T The v-sea oncogene of avian erythroblastosis retrovirus S13: another member of the protein-tyrosine kinase gene family. .P JOURNAL ARTICLE. .W The cloning and sequencing of the oncogene of the avian erythroblastosis virus S13 is described. The oncogene, termed v-sea, was found to be another member of the protein-tyrosine kinase gene family. The oncogene was fused in frame with the retrovirus S13 envelope gene, thus generating a fusion protein with a structure resembling that of a growth factor receptor. Sequence comparisons revealed that the v-sea gene was most closely related to the insulin receptor family of protein-tyrosine kinases, the greatest similarity being with the human MET oncogene. .A Smith DR; Vogt PK; Hayman MJ. .I 125540 .U 89315784 .S Proc Natl Acad Sci U S A 8910; 86(14):5296-300 .M Animal; Antimetabolites/*PD; Glutathione/AI/*ME; Kinetics; Liver/DE/ME; Lung/DE/*ME/UL; Lymphocytes/DE/ME; Male; Methionine Sulfoximine/*AA/PD; Mice; Microscopy, Electron; Mitochondria/DE/*ME; Organoids/DE/*ME; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Glutathione metabolism in the lung: inhibition of its synthesis leads to lamellar body and mitochondrial defects. .P JOURNAL ARTICLE. .W Mice treated with buthionine sulfoximine, an inhibitor of glutathione synthesis, showed striking alterations of morphology of lung type 2 cell lamellar bodies (swelling and disintegration) and mitochondria (degeneration) and of lung capillary endothelial cells (mitochondrial swelling). These effects probably may be ascribed to glutathione deficiency; administration of glutathione monoester protects against them. Measurements of arteriovenous plasma glutathione levels across the lung indicate that the net uptake of glutathione by this organ is substantial. Thus, glutathione exported from the liver to the blood plasma is utilized by the lung which, like the liver, kidney, and lymphocytes (and unlike skeletal muscle), exhibits a high overall rate of glutathione turnover. Intraperitoneal injection of glutathione into buthionine sulfoximine-treated mice leads to very high levels of plasma glutathione without significant increase in the glutathione levels of liver, lung, and lymphocytes; on the other hand, administration of glutathione monoester leads to markedly increased tissue and mitochondrial levels of glutathione. Administration of glutathione monoester (in contrast to glutathione) to control mice also increases mitochondrial glutathione levels. The findings indicate that glutathione is required for mitochondrial integrity and that it probably also functions in the processing and storage of surfactant in lamellar bodies. The morphological changes observed after treatment with buthionine sulfoximine and their prevention by glutathione monoester as well as findings on glutathione metabolism indicate that this tripeptide plays an important role in the lung. The previously observed failure of buthionine sulfoximine-treated mice to gain weight is mainly due to glutathione deficiency in the intestinal mucosa. .A Martensson J; Jain A; Frayer W; Meister A. .I 125541 .U 89315786 .S Proc Natl Acad Sci U S A 8910; 86(14):5306-9 .M Base Sequence; Cell Line; Chromosome Deletion; Gene Expression Regulation; Genes, Regulator/*; Genes, Structural/*; Globin/*GE; Human; Mutation; Plasmids; Promoter Regions (Genetics); Sequence Homology, Nucleic Acid; Transcription, Genetic/*; Transfection. .T Identification of a transcriptional silencer in the 5'-flanking region of the human epsilon-globin gene. .P JOURNAL ARTICLE. .W We have studied the 5'-flanking sequences required for the transcriptional regulation of human epsilon-globin gene expression. A series of deletion mutants of the human epsilon-globin gene 5'-flanking sequences were constructed and linked to the bacterial chloramphenicol acetyltransferase gene. Expression of these constructs was tested in HeLa cells and the human erythroleukemia K-562 cells. By measuring chloramphenicol acetyltransferase activities and mRNA levels we found that the sequence between -177 and -392 base pairs (bp) relative to the mRNA initiation site exerts a negative effect on epsilon-globin promoter activity. This effect is more pronounced in HeLa cells compared with K-562 cells. To further characterize the negative control region we cloned the DNA sequence between -177 and -392 bp either 5' or 3' of the epsilon-globin promoter and in either orientation. Our data indicate that this negative control region inhibits the epsilon-globin promoter activity in a position- and orientation-independent manner, thus suggesting that it is a silencer. In addition, the silencer also inhibits the expression from the Herpesvirus thymidine kinase promoter. Sequence comparison reveals that there are three short regions within the silencer that share extensive homology with those found in other negative control DNA elements. Our results therefore indicate that an upstream silencer element is present in the epsilon-globin gene and that it may play an important role in the control of epsilon-globin gene expression during development. .A Cao SX; Gutman PD; Dave HP; Schechter AN. .I 125542 .U 89315787 .S Proc Natl Acad Sci U S A 8910; 86(14):5310-4 .M Amino Acid Sequence; Base Sequence; Carrier Proteins/*GE; Cloning, Molecular; Comparative Study; Gene Expression Regulation; Genes, Reiterated; Genes, Structural; Human; Molecular Sequence Data; Sequence Homology, Nucleic Acid; Support, Non-U.S. Gov't; Transcription, Genetic; Tretinoin/ME. .T A third human retinoic acid receptor, hRAR-gamma. .P JOURNAL ARTICLE. .W Retinoic acid receptors (RARs) are retinoic acid (RA)-inducible enhancer factors belonging to the superfamily of steroid/thyroid nuclear receptors. We have previously characterized two human RAR (hRAR-alpha and hRAR-beta) cDNAs and have recently cloned their murine cognates (mRAR-alpha and mRAR-beta) together with a third RAR (mRAR-gamma) whose RNA was detected predominantly in skin, a well-known target for RA. mRAR-gamma cDNA was used here to clone its human counterpart (hRAR-gamma) from a T47D breast cancer cell cDNA library. Using a transient transfection assay in HeLa cells and a reporter gene harboring a synthetic RA responsive element, we demonstrate that hRAR-gamma cDNA indeed encodes a RA-inducible transcriptional trans-activator. Interestingly, comparisons of the amino acid sequences of all six human and mouse RARs indicate that the interspecies conservation of a given member of the RAR subfamily (either alpha, beta, or gamma) is much higher than the conservation of all three receptors within a given species. These observations indicate that RAR-alpha, -beta, and -gamma may perform specific functions. We show also that hRAR-gamma RNA is the predominant RAR RNA species in human skin, which suggests that hRAR-gamma mediates some of the retinoid effects in this tissue. .A Krust A; Kastner P; Petkovich M; Zelent A; Chambon P. .I 125543 .U 89315788 .S Proc Natl Acad Sci U S A 8910; 86(14):5315-9 .M Animal; Base Sequence; Cell Line; DNA/IP/*RE; DNA Damage/*; DNA Polymerases; Enhancer Elements (Genetics); Genes/*RE; Genes, Regulator; Molecular Sequence Data; Nucleotide Mapping/*; Plasmids; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Ultraviolet Rays/*. .T Genomic footprinting in mammalian cells with ultraviolet light. .P JOURNAL ARTICLE. .W A simple and accurate genomic primer extension method has been developed to detect ultraviolet footprinting patterns of regulatory protein-DNA interactions in mammalian genomic DNA. The technique can also detect footprinting or sequencing patterns introduced into genomic DNA by other methods. Purified genomic DNA, containing either damaged bases or strand breaks introduced by footprinting or sequencing reactions, is first cut with a convenient restriction enzyme to reduce its molecular weight. A highly radioactive single-stranded DNA primer that is complementary to a region of genomic DNA whose sequence or footprint one wishes to examine is then mixed with 50 micrograms of restriction enzyme-cut genomic DNA. The primer is approximately 100 bases long and contains 85 radioactive phosphates, each of specific activity 3000 Ci/mmol (1 Ci = 37 GBq). A simple and fast method for preparing such primers is described. Following brief heat denaturation at 100 degrees C, the solution of genomic DNA and primer is cooled to 74 degrees C and a second solution containing Taq polymerase (Thermus aquaticus DNA polymerase) and the four deoxynucleotide triphosphates is added to initiate primer extension of genomic DNA. Taq polymerase extends genomic hybridized primer until its polymerization reaction is terminated either by a damaged base or strand break in genomic DNA or by the addition of dideoxynucleotide triphosphates in the polymerization reaction. The concurrent primer hybridization-extension reaction is terminated after 5 hr and unhybridized primer is digested away by mung bean nuclease. Primer-extended genomic DNA is then denatured and electrophoresed on a polyacrylamide sequencing gel, and radioactive primer extension products are revealed by autoradiography. By using this method we demonstrate that it is possible to footprint with ultraviolet light, in intact monkey cells, regulatory protein--DNA interactions along a single copy of a simian virus 40 viral genome integrated into the monkey genome. .A Becker MM; Wang Z; Grossmann G; Becherer KA. .I 125544 .U 89315791 .S Proc Natl Acad Sci U S A 8910; 86(14):5330-4 .M Amino Acid Sequence; Base Sequence; Cloning, Molecular; Codon/GE; DNA/*GE; Human; Liver/EN; Macromolecular Systems; Molecular Sequence Data; Pyruvate Dehydrogenase Complex/*GE; Restriction Mapping; Support, U.S. Gov't, P.H.S.. .T Characterization of cDNAs encoding human pyruvate dehydrogenase alpha subunit. .P JOURNAL ARTICLE. .W A cDNA clone (1423 base pairs) comprising the entire coding region of the precursor form of the alpha subunit of pyruvate dehydrogenase (E1 alpha) has been isolated from a human liver cDNA library in phage lambda gt11. The first 29 amino acids deduced from the open reading frame correspond to a typical mitochondrial targeting leader sequence. The remaining 361 amino acids, starting at the N terminus with phenylalanine, represent the mature mitochondrial E1 alpha peptide. The cDNA has 43 base pairs in the 5' untranslated region and 210 base pairs in the 3' untranslated region, including a polyadenylylation signal and a short poly(A) tract. The nucleotide sequence of human liver E1 alpha cDNA was confirmed by the nucleotide sequences of three overlapping fragments generated from human liver and fibroblast RNA by reverse transcription and DNA amplification by the polymerase chain reaction. This consensus nucleotide sequence of human liver E1 alpha cDNA resolves existing discrepancies among three previously reported human E1 alpha cDNAs and provides the unambiguous reference sequence needed for the characterization of genetic mutations in pyruvate dehydrogenase-deficient patients. .A Ho L; Wexler ID; Liu TC; Thekkumkara TJ; Patel MS. .I 125545 .U 89315792 .S Proc Natl Acad Sci U S A 8910; 86(14):5335-9 .M Barley; Base Sequence; Molecular Sequence Data; Mosaic Viruses/GD/*GE; Mutation; Nucleic Acid Conformation; Plants/GE; RNA, Transfer/*GE; RNA, Viral/*GE; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Telomeric function of the tRNA-like structure of brome mosaic virus RNA. .P JOURNAL ARTICLE. .W Four mutant brome mosaic virus (BMV) RNA3 transcripts, bearing single or double base changes in the 3'-CCAOH terminus of the tRNA-like structure, previously characterized as being deficient in vitro with respect to aminoacylation and replication activities, have now been assayed in vivo for their ability to replicate (in the presence of transcripts of wild-type RNA1 and -2) in barley protoplasts and plants. In tests conducted with protoplasts, irrespective of the time post-infection, all four mutants were fully viable, and the relative levels of both plus and minus strand replication for each mutant were similar to that of the wild type. Inoculation of barley plants with these mutants resulted in phenotypic symptoms and viral yields that were similar to those from wild-type infections. Analysis of each mutant progeny RNA3 indicated that the altered sequence at the 3' terminus was restored to that of wild type. These observations indicate that there is a rapid turnover and correction of the 3' termini of BMV RNAs in vivo. Such correction is commensurate with the action of tRNA nucleotidyltransferase, but it differs from recombination processes that appear to be relatively infrequent for BMV RNA3. These results support the conclusion that the 3'-CCAOH termini of viral tRNA-like structures function analogously to telomeres of chromosomal DNA. .A Rao AL; Dreher TW; Marsh LE; Hall TC. .I 125546 .U 89315795 .S Proc Natl Acad Sci U S A 8910; 86(14):5351-5 .M Hydrogen-Ion Concentration; Kinetics; Lipid Bilayers; Liposomes/*; Models, Theoretical; Nuclear Magnetic Resonance/MT; Phosphatidic Acids/*; Phosphatidylcholines/*; Phosphorus; Support, Non-U.S. Gov't. .T Mechanism of spontaneous vesiculation. .P JOURNAL ARTICLE. .W Both naturally occurring and synthetic phosphatidic acid (PtdOH) molecules show the phenomenon of spontaneous vesiculation on jump in pH value. This method involves a transient increase in pH of smectic PtdOH dispersions to values between 10 and 12. Such a pH increase induces spontaneous vesiculation with the formation of small unilamellar vesicles of diameter less than 50 nm as shown by 31P NMR. Both high-resolution and broad-line 31P NMR were used to study the mechanism of this process. When the pH of unsonicated PtdOH dispersions is raised to pH 10-12, lipid molecules on the outer monolayer of the bilayer become fully ionized. The second pK value of PtdOH in bilayers is 8.6 +/- 0.3, determined by 31P NMR. PtdOH molecules on the inner monolayer remain partially protonated. 31P NMR provides unambiguous evidence that the "pH-jump" treatment produces a pH gradient across the PtdOH bilayer. The orientation of the pH gradient is such that the pH in the external medium is 3-5 pH units higher than the internal pH. Associated with the pH gradient is a transverse packing asymmetry: partially protonated PtdOH molecules in the inner layer of the bilayer are more tightly packed than fully ionized molecules present in the outer layer. The pH gradient generated by the pH jump is proposed as the energy source that drives the spontaneous formation of highly curved vesicles. .A Hauser H. .I 125547 .U 89315796 .S Proc Natl Acad Sci U S A 8910; 86(14):5356-60 .M DNA/*UL; Mathematics; Microscopy/MT; Models, Molecular; Nucleic Acid Conformation; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.. .T Imaging of single uncoated DNA molecules by scanning tunneling microscopy. .P JOURNAL ARTICLE. .W Scanning tunneling microscope images of DNA molecules absorbed onto highly oriented pyrolytic graphite have been obtained. Three methods of deposition and sample preparation have been utilized. In the first method, a highly concentrated solution of DNA is sonicated, and a drop is deposited on freshly cleaved graphite. Under these conditions, the molecules tend to align in a parallel fashion, forming liquid-crystalline phases. In the second method, a solution of DNA is deposited directly on the graphite surface without sonication. In this case, ammonium acetate, a volatile salt, is used to decrease the amount of the residual salt crystals left after drying. In the third method, a solution containing lysed phage particles and DNA is adsorbed onto a graphite surface. The molecules are seen either isolated or in small bundles. The values of height, periodicity, and thickness observed and the handedness of the molecules are consistent with those expected for DNA. In all cases, the molecules were identified by their characteristic periodic structure and because, at higher magnification, no graphite-like structure was detectable on the surface of the molecules. Often the DNA molecules appear to adsorb in areas of the graphite that have many steps and defects. A mechanism that explains the magnitude of the tunneling currents measured in DNA is proposed. This mechanism, in turn, suggests a general method by which large insulating molecules can be rendered conductive. .A Keller D; Bustamante C; Keller RW. .I 125548 .U 89315798 .S Proc Natl Acad Sci U S A 8910; 86(14):5366-70 .M Actins/ME; Adenosine Triphosphatase/ME; Animal; Macromolecular Systems; Mathematics; Muscles/*PH; Myosin/*ME; Peptide Fragments/AN; Rabbits; Spectrometry, Fluorescence; Stress, Mechanical; Support, Non-U.S. Gov't. .T Effect of negative mechanical stress on the orientation of myosin cross-bridges in muscle fibers. .P JOURNAL ARTICLE. .W The effect of positive and negative stress on myosin cross-bridge orientation in glycerinated muscle fibers was investigated by using fluorescence polarization spectroscopy of the emission from the covalent label tetramethyl-rhodamine-5-(and -6)-iodoacetamide (IATR) specifically modifying sulfhydryl one (SH1) on the myosin heavy chain. Positive tension was applied by stretching the fiber in rigor. Negative tension was applied in two steps by using a protocol introduced by Goldman et al. [Goldman, Y. E., McCray, J. A. & Vallette, D. P. (1988) J. Physiol. (London) 398, 75P]: relaxing a fiber at resting length and stretching it until the relaxed tension is appreciable and then placing the fiber in rigor and releasing the tension onto the rigor cross-bridges. We found, as have others, that positive tension has no effect on the fluorescence polarization spectrum from the SH1-bound probe, indicating that the cross-bridge does not rotate under these conditions. Negative tension, however, causes a change in the fluorescence polarization spectrum that indicates a probe rotation. The changes in the polarization spectrum from negative stress are partially reversed by the subsequent application of positive stress. It appears that negative tension strains the cross-bridge, or the cross-bridge domain containing SH1, and causes it to rotate. .A Burghardt TP; Ajtai K. .I 125549 .U 89315800 .S Proc Natl Acad Sci U S A 8910; 86(14):5380-4 .M Animal; DNA/GE; Female; Intercellular Junctions/*PH; Kinetics; Membrane Potentials; Membrane Proteins/GE/*PH; Oocytes/PH; RNA, Messenger/GE; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Transcription, Genetic; Xenopus. .T Formation of hybrid cell-cell channels. .P JOURNAL ARTICLE. .W The oocyte cell-cell channel assay was used to demonstrate that connexin-43 is a cell-cell channel-forming protein as previously shown for connexin-32. Expression of connexin-32 in one and connexin-43 in the other oocyte of a pair results in the formation of junctional conductances at rates similar to those observed when only one or the other connexin is expressed in both oocytes of a pair. This suggests that hybrid cell-cell channels form in the oocyte system. Hybrid channels also form when a connexin-43 mRNA-injected oocyte is paired with a noninjected oocyte expressing endogenous connexin. The latter hybrids have properties apparently contributed by both types of hemichannels. Pure connexin-43 channels are not voltage gated, whereas pure oocyte channels are voltage dependent; hybrids of these channels rectify. .A Werner R; Levine E; Rabadan-Diehl C; Dahl G. .I 125550 .U 89315801 .S Proc Natl Acad Sci U S A 8910; 86(14):5385-9 .M Animal; Carcinoma; Diffusion; Ear/BS; Male; Microcirculation/*ME; Microscopy, Fluorescence/MT; Photochemistry; Rabbits; Regional Blood Flow; Serum Albumin, Bovine/*ME; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Tumor Cells, Cultured/*ME. .T Direct measurement of interstitial convection and diffusion of albumin in normal and neoplastic tissues by fluorescence photobleaching. .P JOURNAL ARTICLE. .W Macromolecular transport through the interstitial space of a tissue occurs by convection and diffusion. The convective component of transport results from interstitial fluid flow. There have been no direct measurements of the magnitude or direction of interstitial fluid flow in tissues to date. Using fluorescence recovery after photobleaching, we have measured interstitial fluid velocities and the diffusion coefficient of bovine serum albumin in normal and neoplastic tissues grown in a thin, transparent window in the ear of a rabbit. A well-defined laser beam was focused on a region within the interstitium of the fluorescence-bathed tissue. A short pulse of laser irradiation extinguished the fluorescence emanating from this selected region. The recovery of fluorescence due to diffusion and convection within the medium was monitored and analyzed to yield values of the diffusion coefficient and the fluid velocity. The average fluid velocity was about 0.6 microns/s, and albumin diffusion coefficients were 5.8 +/- 1.3 x 10(-7) cm2/s and 6.3 +/- 1.9 x 10(-7) cm2/s in normal and neoplastic tissues, respectively. The interstitial fluid flow, in general, was directed into postcapillary venules. The results obtained in this study should provide the impetus for further investigation into the diffusion and convection in various tissues under normal and pathological conditions. .A Chary SR; Jain RK. .I 125551 .U 89315811 .S Proc Natl Acad Sci U S A 8910; 86(14):5434-8 .M Adipose Tissue; Animal; Cell Differentiation/*; Cell Line; Fibroblasts; Gene Expression Regulation/*; Genes, Regulator/*; Genetic Vectors; Human; Liver; Melanoma; Moloney Sarcoma Virus/GE; Muscles/*CY; Neuroblastoma; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Transfection. .T Activation of muscle-specific genes in pigment, nerve, fat, liver, and fibroblast cell lines by forced expression of MyoD. .P JOURNAL ARTICLE. .W MyoD is a master regulatory gene for myogenesis. Under the control of a retroviral long terminal repeat, MyoD was expressed in a variety of differentiated cell types by using either a DNA transfection vector or a retrovirus. Expression of muscle-specific proteins was observed in chicken, human, and rat primary fibroblasts and in differentiated melanoma, neuroblastoma, liver, and adipocyte lines. The ability of MyoD to activate muscle genes in a variety of differentiated cell lines suggests that no additional tissue-specific factors other than MyoD are needed to activate the downstream program for terminal muscle differentiation or that, if such factors exist, they are themselves activated by MyoD expression. .A Weintraub H; Tapscott SJ; Davis RL; Thayer MJ; Adam MA; Lassar AB; Miller AD. .I 125552 .U 89315812 .S Proc Natl Acad Sci U S A 8910; 86(14):5439-43 .M Animal; Cell Line; Chromosome Deletion; Gene Expression Regulation/*; Genes, Regulator/*; Genes, Structural/*; Globin/*GE; Human; Mice; Plasmids; Restriction Mapping; RNA, Messenger/GE; Support, U.S. Gov't, P.H.S.; Transcription, Genetic. .T Molecular analysis of the human beta-globin locus activation region. .P JOURNAL ARTICLE. .W Recently, DNA sequences containing four erythroid-specific DNase I hypersensitive sites within 20 kilobases 5' of the human epsilon-globin gene have been identified as an important cis-acting regulatory element, the locus activation region (LAR). Subfragments of the LAR, containing either all or only the two 5' or two 3' hypersensitive sites were linked to the human beta-globin gene and analyzed for their effect on globin gene expression in stably transformed mouse erythroleukemia (MEL) cells. Constructs containing all four of the hypersensitive sites increase beta-globin mRNA levels 8- to 13-fold, while constructs with only the 5' or 3' sites increase globin expression to a lesser extent. No effect was seen when the constructs were assayed in 3T3 fibroblasts. All of the LAR derivatives form hypersensitive sites at the corresponding sequence position in MEL cells prior to and after induction of MEL cell differentiation. However, in 3T3 fibroblasts only the hypersensitive site corresponding to the previously described erythroid-specific -10.9 site was formed. .A Forrester WC; Novak U; Gelinas R; Groudine M. .I 125553 .U 89315814 .S Proc Natl Acad Sci U S A 8910; 86(14):5449-53 .M Amino Acid Sequence; Animal; Antibodies; Base Sequence; Chick Embryo; Chickens; Cloning, Molecular; DNA/*GE; Immunoblotting; Molecular Sequence Data; Molecular Weight; Protein-Tyrosine Kinase/*GE; Sequence Homology, Nucleic Acid; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Tyrosine/*AA/AN/IM. .T Identification of a developmentally regulated protein-tyrosine kinase by using anti-phosphotyrosine antibodies to screen a cDNA expression library. .P JOURNAL ARTICLE. .W To identify the protein-tyrosine kinases that are expressed during chicken embryonic development, a 10-day chicken embryo cDNA expression library was screened with anti-phosphotyrosine antibodies. Of the positive clones isolated, many encoded the same protein-tyrosine kinase, which we designate Cek1 (chicken embryo kinase 1). Its amino acid sequence suggests that the Cek1 protein is a transmembrane tyrosine kinase and presumably the receptor for an unknown ligand. Antibodies prepared to the cloned Cek1 kinase recognize, in immunoblotting experiments, two protein bands with apparent molecular weights of 100,000 and 110,000. The Cek1 protein was detected in many chicken embryonic tissues, but not in the corresponding adult tissues (with the exception of brain). The Cek1 kinase appears to be very closely related to two protein-tyrosine kinases whose partial sequences have been recently determined, human Flg and mouse Bek. Cloning using anti-phosphotyrosine antibodies has allowed us to detect, in addition to Cek1, several other protein-tyrosine kinases that are expressed during chicken embryonic development, some of which have not been previously identified. .A Pasquale EB; Singer SJ. .I 125554 .U 89315815 .S Proc Natl Acad Sci U S A 8910; 86(14):5454-8 .M Alcohol Dehydrogenase/*GE; Amino Acid Sequence; Animal; Base Sequence; Comparative Study; DNA/*GE; Evolution/*; Gene Expression Regulation; Genes, Reiterated/*; Genes, Structural/*; Hominidae/*GE; Human; Liver/EN; Molecular Sequence Data; Papio/*GE; Primates/*GE; Restriction Mapping; Sequence Homology, Nucleic Acid; Support, Non-U.S. Gov't. .T Cloning and sequencing of cDNA encoding baboon liver alcohol dehydrogenase: evidence for a common ancestral lineage with the human alcohol dehydrogenase beta subunit and for class I ADH gene duplications predating primate radiation. .P JOURNAL ARTICLE. .W The baboon has at least five alcohol dehydrogenases (ADH; alcohol:NAD+ oxidoreductase, EC 1.1.1.1) and has distinct liver and kidney class I isozymes. A rat liver class I ADH partial cDNA was used to screen a baboon liver cDNA library. A cDNA clone was isolated and sequenced and found to contain the entire coding region for baboon liver ADH, 12 nucleotides of the 5' noncoding region, and 256 nucleotides of the 3' noncoding region. The amino acid sequence deduced from this cDNA most closely resembles that of human liver ADH beta subunit (ADH-beta): 363 of 374 residues were identical. This suggested that baboon liver class I ADH is of the same ancestral lineage as the human ADH-beta. In contrast to human liver, only a single ADH-beta transcript is observed in baboon liver. A comparison of human and baboon ADH 3' noncoding regions suggests that a single nucleotide change in a polyadenylylation signal consensus sequence may, in part, be responsible for the generation of ADH-beta transcripts with variable-length 3' ends in human liver. A nucleotide substitution rate of 0.5 x 10(-9) substitutions per site per year for primate class I ADH genes was deduced from the data, which suggests that the alpha-beta gamma separation of human ADH genes occurred about 60 million years ago, and that primate class I ADH gene duplications predated primate radiation. .A Trezise AE; Godfrey EA; Holmes RS; Beacham IR. .I 125555 .U 89315816 .S Proc Natl Acad Sci U S A 8910; 86(14):5459-63 .M Animal; Chromosome Mapping; Comparative Study; Drosophila/GE; Evolution/*; Genes, Homeo Box/*; Human; Mice; Rats; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Vertebrates/*GE. .T Two steps in the evolution of Antennapedia-class vertebrate homeobox genes. .P JOURNAL ARTICLE. .W Antennapedia-class vertebrate homeobox genes have been classified with regard to their chromosomal locations and nucleotide sequence similarities within the 183-base-pair homeobox domain. The results of these comparisons support the view that in mammals and most likely the vertebrates, four clusters of homeobox genes exist that were created by duplications of an entire primordial gene cluster. We present evidence that this primordial cluster arose by local gene duplications of homeoboxes that were present before the divergence of arthropods and chordates. Sequence analyses indicate that the expansion of the primordial gene cluster complex was accompanied by diversification, whereas conservation predominated after the duplications of entire homeobox gene clusters. .A Kappen C; Schughart K; Ruddle FH. .I 125556 .U 89315817 .S Proc Natl Acad Sci U S A 8910; 86(14):5464-8 .M Animal; Chromosome Mapping; Crosses, Genetic/*; Drosophila/*GE; Evolution; Female; Male; Support, U.S. Gov't, P.H.S.. .T Genetics of sexual isolation between two sibling species, Drosophila simulans and Drosophila mauritiana. .P JOURNAL ARTICLE. .W Drosophila simulans and Drosophila mauritiana are sibling species that show substantial sexual isolation in one of their two reciprocal hybridizations. Genetic analysis reveals that in females this isolation is caused by at least one recessive gene on each autosome, while the X chromosome has little or no effect. Our results, combined with those of previous studies, show that in Drosophila the genetics of sexual isolation differs from that of postzygotic reproductive isolation, which invariably involves large effects of the X chromosome. .A Coyne JA. .I 125557 .U 89315818 .S Proc Natl Acad Sci U S A 8910; 86(14):5469-72 .M Animal; Cell Nucleus/AN; Diploidy/*; DNA/AN/GE; Flow Cytometry; Trypanosoma/*GE; Trypanosoma brucei brucei/GE; Trypanosoma congolense/GE. .T Evidence for diploidy in metacyclic forms of African trypanosomes. .P JOURNAL ARTICLE. .W The DNA contents of bloodstream form trypanosomes (life cycle stages circulating in the blood of the vertebrate host) of four African Trypanosoma species and of metacyclic forms (the life cycle stage that is injected into the vertebrate by the tsetse fly during its bite) of the same four species were measured by cytofluorometry of individual cells or nuclei. The results showed unambiguously that the metacyclic forms cannot be considered to be products of meiosis containing only half of the DNA of bloodstream forms, in contrast to what was previously reported for Trypanosoma brucei [Zampetti-Bosseler, F., Schweizer, J., Pays, E., Jenni, L. & Steinert, M. (1986) Proc. Natl. Acad. Sci. USA 83, 6063-6064] during an attempt to localize the gametes in the life cycle after experimental evidence of sexual gene exchange in this parasite was reported. .A Kooy RF; Hirumi H; Moloo SK; Nantulya VM; Dukes P; Van der Linden PM; Duijndam WA; Janse CJ; Overdulve JP. .I 125558 .U 89315820 .S Proc Natl Acad Sci U S A 8910; 86(14):5478-82 .M Chromosome Deletion; Cloning, Molecular; Drug Resistance, Microbial; Genes, Bacterial; Genetic Vectors/*; Halobacterium/DE/*GE; Lovastatin/PD; Mutation; Restriction Mapping; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Transformation, Bacterial. .T Shuttle vectors for the archaebacterium Halobacterium volcanii. .P JOURNAL ARTICLE. .W Progress in archaebacterial molecular biology requires tools for genetic analysis. We describe vectors that can be selected and maintained in either Halobacterium volcanii or Escherichia coli. A genetic determinant for resistance to the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor mevinolin was isolated by "shotgun cloning" into a derivative of the endogenous H. volcanii plasmid pHV2, to form pWL2, which transforms sensitive H. volcanii to mevinolin resistance at high frequency. The resistance determinant, portions of pHV2, and an ampicillin- and tetracycline-resistance-conferring pBR322 derivative, pAT153, were ligated together to form the shuttle vectors pWL101 and pWL102. We describe conditions for the use of these vectors and provide preliminary definition of regions essential for drug resistance and for plasmid replication and maintenance. .A Lam WL; Doolittle WF. .I 125559 .U 89315821 .S Proc Natl Acad Sci U S A 8910; 86(14):5483-6 .M Amino Acid Sequence; Animal; Base Sequence; Comparative Study; Drosophila/*GE; Evolution/*; Genes, Homeo Box/*; Molecular Sequence Data; Sequence Homology, Nucleic Acid; Species Specificity; Support, Non-U.S. Gov't. .T The homeotic gene spalt (sal) evolved during Drosophila speciation. .P JOURNAL ARTICLE. .W The region-specific homeotic gene spalt (sal) acts in two separate domains in the head and tail region of the Drosophila melanogaster embryo. Based on comparative morphology, sal is likely to be involved in the establishment of the head during the evolution of invertebrates and thus, it should be conserved. We have analyzed the conservation of the segmentation genes Kruppel (Kr) and even-skipped (eve) in parallel with sal coding sequences in several Drosophila species that are evolutionarily separated by up to 60 million years. To our surprise, sal sequences appear to be conserved in the Sophophora subgenus of the Drosophila genus but not in the Drosophila subgenus. On the other hand, the segmentation and other homeotic genes are conserved in the Drosophila subgroup as well. Our data suggest that sal encodes an accessory function that evolved relatively late during Drosophila speciation rather than playing a fundamental evolutionary role similar to that of other homeotic genes. .A Reuter D; Schuh R; Jackle H. .I 125560 .U 89315822 .S Proc Natl Acad Sci U S A 8910; 86(14):5487-91 .M Animal; Animals, Newborn; Blotting, Northern; Blotting, Southern; DNA/GE; DNA, Neoplasm/GE; Evolution; Gene Amplification; Gene Expression Regulation/*; Human; Lymphoma/*GE/MI; Mice; Moloney Leukemia Virus/*GE; Proto-Oncogenes/*; Rats; Rats, Inbred F344; Restriction Mapping; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Activation of the Mlvi-1/mis1/pvt-1 locus in Moloney murine leukemia virus-induced T-cell lymphomas. .P JOURNAL ARTICLE. .W The Mlvi-1/mis-1/pvt-1 locus, located approximately 270 kilobase pairs 3' of the c-myc protooncogene, was originally discovered as a common region of provirus integration in Moloney murine leukemia virus-induced rat T-cell lymphomas. The same locus was shown subsequently to be coamplified with c-myc and to be involved in chromosomal translocations in a variety of human and animal neoplasms. Provirus integration in Mlvi-1 in Moloney murine leukemia virus-induced rat T-cell lymphomas activates the c-myc protooncogene. The studies reported here were aimed to determine whether, in addition to the activation of c-myc, provirus integration affected the expression of other neighboring genes. Provirus integration was shown to occur in three clusters separated by regions of uninterrupted DNA. The proviruses in all three clusters had integrated in a single-transcriptional orientation, and they appeared intact. Systematic hybridization of Mlvi-1 clones to rat, mouse, and human genomic DNA revealed three patches of evolutionarily conserved sequences. Two of them were mapped in regions targeted by the provirus, and the third was mapped immediately 5' to the provirus clusters. A probe derived from the conserved sequences 5' of the integrated proviruses detected a tumor-specific RNA transcript in tumors carrying a provirus in Mlvi-1 or in the neighboring Mlvi-4 and c-myc loci. The highest level of RNA transcript expression, however, was seen in a CD4+ CD8+ tumor cell line that was not carrying a provirus in this region. We conclude that provirus insertion in this region activates both c-myc and another gene that is located in the immediate vicinity of the integrated Mlvi-1 proviruses and may be developmentally regulated in T cells. .A Tsichlis PN; Shepherd BM; Bear SE. .I 125561 .U 89315825 .S Proc Natl Acad Sci U S A 8910; 86(14):5502-6 .M Base Sequence; Chromosome Deletion; DNA, Neoplasm/GE; Exons; Eye Neoplasms/*GE; Genes/*; Human; Introns; Molecular Sequence Data; Promoter Regions (Genetics); Restriction Mapping; Retinoblastoma/*GE; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Transcription, Genetic. .T Structure of the human retinoblastoma gene. .P JOURNAL ARTICLE. .W Complete inactivation of the human retinoblastoma gene (RB) is believed to be an essential step in tumorigenesis of several different cancers. To provide a framework for understanding inactivation mechanisms, the structure of RB was delineated. The RB transcript is encoded in 27 exons dispersed over about 200 kilobases (kb) of genomic DNA. The length of individual exons ranges from 31 to 1889 base pairs (bp). The largest intron spans greater than 60 kb and the smallest one has only 80 bp. Deletion of exons 13-17 is frequently observed in various types of tumors, including retinoblastoma, breast cancer, and osteosarcoma, and the presence of a potential "hot spot" for recombination in the region is predicted. A putative "leucine-zipper" motif is exclusively encoded by exon 20. The detailed RB structure presented here should prove useful in defining potential functional domains of its encoded protein. Transcription of RB is initiated at multiple positions and the sequences surrounding the initiation sites have a high G + C content. A typical upstream TATA box is not present. Localization of the RB promoter region was accomplished by utilizing a heterologous expression system containing a bacterial chloramphenicol acetyltransferase gene. Deletion analysis revealed that a region as small as 70 bp is sufficient for RB promoter activity, similar to other previously characterized G + C-rich gene promoters. Several direct repeats and possible stem-and-loop structures are found in the promoter region. No enhancer element was detected within the 7.3 kb of upstream sequence studied. Several features of the RB promoter are reminiscent of the characteristics associated with many "housekeeping" genes, consistent with its ubiquitous expression pattern. .A Hong FD; Huang HJ; To H; Young LJ; Oro A; Bookstein R; Lee EY; Lee WH. .I 125562 .U 89315827 .S Proc Natl Acad Sci U S A 8910; 86(14):5512-6 .M Animal; Cell Line; Cell Survival/RE; Cloning, Molecular/*; DNA Repair/*; DNA Replication/RE; Embryo; Genes/*; Genetic Complementation Test; Human; Mice; Plasmids; Restriction Mapping; Support, Non-U.S. Gov't; Transfection/*; Ultraviolet Rays; Xeroderma Pigmentosum/*GE. .T Molecular cloning of a mouse DNA repair gene that complements the defect of group-A xeroderma pigmentosum. .P JOURNAL ARTICLE. .W For isolation of the gene responsible for xeroderma pigmentosum (XP) complementation group A, plasmid pSV2gpt and genomic DNA from a mouse embryo were cotransfected into XP2OSSV cells, a group-A XP cell line. Two primary UV-resistant XP transfectants were isolated from about 1.6 X 10(5) pSV2gpt-transformed XP colonies. pSV2gpt and genomic DNA from the primary transfectants were again cotransfected into XP2OSSV cells and a secondary UV-resistant XP transfectant was obtained by screening about 4.8 X 10(5) pSV2gpt-transformed XP colonies. The secondary transfectant retained fewer mouse repetitive sequences. A mouse gene that complements the defect of XP2OSSV cells was cloned into an EMBL3 vector from the genome of a secondary transfectant. Transfections of the cloned DNA also conferred UV resistance on another group-A XP cell line but not on XP cell lines of group C, D, F, or G. Northern blot analysis of poly(A)+ RNA with a subfragment of cloned mouse DNA repair gene as the probe revealed that an approximately 1.0 kilobase mRNA was transcribed in the donor mouse embryo and secondary transfectant, and approximately 1.0- and approximately 1.3-kilobase mRNAs were transcribed in normal human cells, but none of these mRNAs was detected in three strains of group-A XP cells. These results suggest that the cloned DNA repair gene is specific for group-A XP and may be the mouse homologue of the group-A XP human gene. .A Tanaka K; Satokata I; Ogita Z; Uchida T; Okada Y. .I 125563 .U 89315831 .S Proc Natl Acad Sci U S A 8910; 86(14):5532-6 .M Animal; Antibodies/*GE; Antibody Diversity; Antigen-Antibody Complex/*; Antigens/*; Base Sequence; Binding Sites; Cell Line; Computer Simulation; Enzyme-Linked Immunosorbent Assay; Gene Rearrangement/*; Models, Molecular; Molecular Sequence Data; Mutation; Phosphorylcholine/IM; Protein Conformation; Structure-Activity Relationship; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.. .T Significant structural and functional change of an antigen-binding site by a distant amino acid substitution: proposal of a structural mechanism. .P JOURNAL ARTICLE. .W To study the molecular basis for antibody diversity and the structural basis for antigen binding, we have characterized the loss of phosphocholine (P-Cho) binding both experimentally and computationally in U10, a somatic mutant of the antibody S107. Nucleotide sequencing of U10 shows a single base change in JH1, substituting Asp-101 with Ala, over 9 A distant from the P-Cho-binding pocket. Probing with antiidiotypic antibodies suggests local, not global, conformational changes. Computational results support a specific structural mechanism for the loss of P-Cho binding. The U10 mutation eliminates the charged interaction between Asp-101 and Arg-94, which allows the Arg-94 side chain to disrupt P-Cho binding sterically and electrostatically by folding into the P-Cho-binding site. These results specifically show the importance of the Arg-94 to Asp-101 side chain salt bridge in the heavy-chain CDR3 conformation and suggest that residues distant from the binding site play an important role in antibody diversity and inducible complementarity. .A Chien NC; Roberts VA; Giusti AM; Scharff MD; Getzoff ED. .I 125564 .U 89315840 .S Proc Natl Acad Sci U S A 8910; 86(14):5575-9 .M Amino Acid Sequence; Animal; Blood Proteins/GE/*PH; Cloning, Molecular; Comparative Study; Complement 4/GE/*PH; DNA/GE; Hemolysis; Human; Mice; Molecular Sequence Data; Mutation; Oligonucleotide Probes; Plasmids; Sequence Homology, Nucleic Acid; Support, U.S. Gov't, P.H.S.. .T Murine complement component C4 and sex-limited protein: identification of amino acid residues essential for C4 function. .P JOURNAL ARTICLE. .W Murine sex-limited protein (Slp) is an isotype of murine complement component C4 that shares 95% sequence identity with C4 as well as the intramolecular thioester necessary for C4 function but has no complement activity. Slp is nonfunctional at least in part because it is not cleaved by the activated form of complement protease C1s (C1s), which proteolytically activates C4 in the classical complement pathway. Slp is also distinct from C4 in that its expression in some mouse strains is under testosterone control. In the present studies, we used site-directed mutagenesis of C4 and expression of the mutant proteins in cultured cells to identify the amino acid substitutions in Slp that are responsible for resistance to C1s cleavage. We focused on sequence changes immediately downstream of the cleavage site in C4 because the arginine at that site is conserved in Slp, but the downstream sequences diverge substantially, with six differences in the first 7 residues followed by a 3-residue deletion in Slp. We found that a C4 mutant carrying only the 3-residue deletion is not cleaved by C1s and has essentially no hemolytic activity, whereas a mutant carrying only the six replacement changes is cleaved by C1s and has normal hemolytic activity. Both mutants have intact thioesters. A third mutant in which two acidic residues in the segment deleted in Slp were replaced by aliphatic residues is also cleaved by C1s, has an intact thioester group, and has normal hemolytic activity. These results indicate that the downstream mutations are responsible for the resistance of Slp to C1s cleavage and suggest that the length rather than the specific sequence of this segment is critical in determining susceptibility to the protease. .A Ogata RT; Cooper NR; Bradt BM; Mathias P; Picchi MA. .I 125565 .U 89315842 .S Proc Natl Acad Sci U S A 8910; 86(14):5585-9 .M Breast Neoplasms; Carbon Isotopes; Cell Line; Clone Cells; Cycloheximide/*PD; Dactinomycin/*PD; Estradiol/*PD; Female; Glucose/*ME; Glutamates/ME; Glycolysis/DE; Human; Lactates/ME; Nuclear Magnetic Resonance/MT; Phospholipids/*ME; Phosphorus; Support, U.S. Gov't, P.H.S.; Tamoxifen/*PD; Tumor Cells, Cultured/DE/*ME. .T Early estrogen-induced metabolic changes and their inhibition by actinomycin D and cycloheximide in human breast cancer cells: 31P and 13C NMR studies. .P JOURNAL ARTICLE. .W Metabolic changes following estrogen stimulation and the inhibition of these changes in the presence of actinomycin D and cycloheximide were monitored continuously in perfused human breast cancer T47D clone 11 cells with 31P and 13C NMR techniques. The experiments were performed by estrogen rescue of tamoxifen-treated cells. Immediately after perfusion with estrogen-containing medium, a continuous enhancement in the rates of glucose consumption, lactate production by glycolysis, and glutamate synthesis by the Krebs cycle occurred with a persistent 2-fold increase at 4 hr. The content of phosphocholine had increased by 10% to 30% within the first hour of estrogen stimulation, but the content of the other observed phosphate metabolites as well as the pH remained unchanged. Pretreatment with either actinomycin D or cycloheximide, at concentrations known to inhibit mRNA and protein synthesis, respectively, and simultaneous treatment with estrogen and each inhibitor prevented the estrogen-induced changes in glucose metabolism. This suggested that the observed estrogen stimulation required synthesis of mRNA and protein. These inhibitors also modulated several metabolic activities that were not related to estrogen stimulation. The observed changes in the in vivo kinetics of glucose metabolism may provide a means for the early detection of the response of human breast cancer cells to estrogen versus tamoxifen treatment. .A Neeman M; Degani H. .I 125566 .U 89315844 .S Proc Natl Acad Sci U S A 8910; 86(14):5595-9 .M Acquired Immunodeficiency Syndrome/*MI; Bone Marrow/PA; Human; HIV-1/*GE/IP; Megakaryocytes/*IM/UL; Microscopy, Electron; RNA, Viral/GE/*IP; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Vacuoles/UL. .T Megakaryocytes of human immunodeficiency virus-infected individuals express viral RNA. .P JOURNAL ARTICLE. .W The pathogenesis of thrombocytopenia associated with human immunodeficiency virus (HIV) infection is not fully understood. Immune mechanisms provide a partial explanation but fail to account for a lack of compensatory megakaryocytosis, the rapid reversal after treatment with azidothymidine, and the ultrastructural aberrations seen in the megakaryocytes of patients with acquired immunodeficiency syndrome. Therefore, a direct effect of HIV on megakaryocytes was investigated. The bone marrow of HIV seropositive individuals was analyzed ultrastructurally, and the megakaryocytes of 10 thrombocytopenic patients were subjected to in situ hybridization with a HIV RNA probe. The structural aberrations in HIV megakaryocytes were distinct from those in HIV-negative immune thrombocytopenias, and the megakaryocytes of 10 of 10 patients examined by in situ hybridization unambiguously expressed viral RNA. Therefore, it is likely that direct infection of megakaryocytes with HIV-1 is one mechanism for the decrease in platelet production. .A Zucker-Franklin D; Cao YZ. .I 125567 .U 89315845 .S Proc Natl Acad Sci U S A 8910; 86(14):5600-4 .M Animal; Blood Platelets/DE/*PH; Dogs; Human; In Vitro; Kinetics; Muscle Contraction/DE; Muscle, Smooth, Vascular/DE/*PH; Platelet Aggregation Inhibitors/*PD; Prostaglandin Endoperoxides, Synthetic/PD; Saphenous Vein/DE/PH; Stereoisomers; Structure-Activity Relationship; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Thromboxane A2/*AA/PD. .T Difluorothromboxane A2 and stereoisomers: stable derivatives of thromboxane A2 with differential effects on platelets and blood vessels. .P JOURNAL ARTICLE. .W The present study reports on the selective effects on human platelets and canine saphenous veins of four stable difluorinated analogues and thromboxane A2 (TXA2), in which the characteristic 2,6-dioxa[3.1.1]bicycloheptane structure of TXA2 has been retained. The four compounds differ in their stereochemistry of the 5,6 double bond and/or the 15-hydroxyl group. Only 10,10-difluoro-TXA2 (compound I) with the natural stereochemistry of TXA2 was an agonist in both platelets and canine saphenous veins (EC50 = 36 +/- 3.6 nM and 3.7 +/- 0.8 nM, respectively). (15R)-10,10-Difluoro-TXA2 (compound II), (5E)-10,10-difluoro-TXA2 (compound III), and (5E,15R)-10,10-difluoro-TXA2 (compound IV) were antagonists of platelet aggregation stimulated by compound I (Kd = 98 +/- 46 nM, 140 +/- 42 nM, and 1450 +/- 350 nM, respectively). However, compounds II, III, and IV stimulated contraction of canine saphenous veins (EC50 = 36 +/- 4.4 nM, 31 +/- 6.8 nM, and 321 +/- 50 nM, respectively). All four compounds could displace the TXA2/prostaglandin H2 antagonist 9,11-dimethylmethano-11,12-methano-16-(3- 125I-4-hydroxyphenyl)-13,14-dihydro-13-aza-15 alpha beta-omega-tetranor-TXA2 from its platelet receptor (Kd values = 100 +/- 30 nM, compound I; 280 +/- 60 nM, compound II; 230 +/- 70 nM, compound III; and 1410 +/- 1020 nM, compound IV). These results support the existence of two subtypes of TXA2/prostaglandin H2 receptors and emphasize the importance of the stereochemical requirements of these TXA2 analogues for interaction with these receptors. These stable fluorinated TXA2 analogues should prove useful tools for the further characterization of these and other TXA2/prostaglandin H2 receptors. .A Morinelli TA; Okwu AK; Mais DE; Halushka PV; John V; Chen CK; Fried J. .I 125568 .U 89315846 .S Proc Natl Acad Sci U S A 8910; 86(14):5605-9 .M Adult; Comparative Study; DNA/IP/*RE; Erythema; Human; Pyrimidine Dimers/*AN; Skin/*RE; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Ultraviolet Rays/*. .T Wavelength dependence of pyrimidine dimer formation in DNA of human skin irradiated in situ with ultraviolet light. .P JOURNAL ARTICLE. .W The UV components of sunlight are believed to be a major cause of human skin cancer, and DNA is thought to be the principal molecular target. Alterations of the intensity and wavelength distribution of solar UV radiation reaching the surface of the earth, for example by depletion of stratospheric ozone, will change the effectiveness of solar radiation in damaging DNA in human skin. Evaluation of the magnitude of such effects requires knowledge of the altered sunlight spectrum and of the action spectrum for damaging DNA in human skin. We have determined an action spectrum for the frequency of pyrimidine dimer formation induced in the DNA of human skin per unit dose of UV incident on the skin surface. The peak of this action spectrum is near 300 nm and decreases rapidly at both longer and shorter wavelengths. The decrease in our action spectrum for wavelengths less than 300 nm is attributed to the absorption of the upper layers of the skin, an in situ effect that is inherently included in our measurements. Convolution of the dimer action spectrum with the solar spectra corresponding to a solar angle of 40 degrees under current levels of stratospheric ozone (0.32-cm O3 layer) and those for 50% ozone depletion (0.16-cm O3 layer), indicate about a 2.5-fold increase in dimer formation. If the action spectrum for DNA damage that results in skin cancer resembles that for dimer induction in skin, our results, combined with epidemiological data, suggest that a 50% decrease in stratospheric ozone would increase the incidence of nonmelanoma skin cancers among white males in Seattle, Washington, by 7.5- to 8-fold, to a higher incidence than is presently seen in the corresponding population of Albuquerque, New Mexico. .A Freeman SE; Hacham H; Gange RW; Maytum DJ; Sutherland JC; Sutherland BM. .I 125569 .U 89315848 .S Proc Natl Acad Sci U S A 8910; 86(14):5615-9 .M Adenoviruses, Human/*GE; Animal; Blotting, Northern; Chimera; Genes, MHC Class I; Genes, Viral; Human; Mammary Cancer Virus/GE; Mice; Mice, Transgenic; Nucleic Acid Hybridization; Oncogene Proteins, Viral/*GE; Plasmids; Repetitive Sequences, Nucleic Acid; Stomach Neoplasms/*GE/MI/PA; Transcription, Genetic. .T Transgenic mouse model for human gastric carcinoma. .P JOURNAL ARTICLE. .W To understand the pathogenesis that may be induced by human adenovirus type 12 (Ad12), we have generated transgenic mice carrying the Ad12 early region 1 under control of the mouse mammary tumor virus long terminal repeat. Eleven of 11 male founder mice, but only 2 of 12 females, died between 3 to 4 mo of age. Death was associated with presence of tumors at or near the squamocolumnar junction of the stomach. Microscopically, these multifocal tumors appeared to arise from hyperplastic epithelium and showed features consistent with adenocarcinoma or adenosquamous carcinoma. High levels of expression of both the Ad12 E1A and E1B genes were seen in the tumor-bearing stomach. Various levels of expression were also detected in other tissues, although the stomach was the only organ with detectable pathology. These observations suggest an organ-specific action of the Ad12 early region 1 gene products. This transgenic mouse model provides an experimental system for studying the development of human carcinomas at sites of transition from squamous to columnar epithelium. .A Koike K; Hinrichs SH; Isselbacher KJ; Jay G. .I 125570 .U 89315850 .S Proc Natl Acad Sci U S A 8910; 86(14):5626-30 .M Animal; Base Sequence; Cells, Cultured; Coronaviridae/*GE; Gastroenteritis Virus of Swine/*GE; Genes, Viral; Kinetics; Male; Molecular Sequence Data; Oligonucleotide Probes; Replicon/*; RNA, Messenger/BI/*GE; RNA, Viral/BI/*GE; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Swine; Testis/CY. .T Coronavirus subgenomic minus-strand RNAs and the potential for mRNA replicons. .P JOURNAL ARTICLE. .W The genome of the porcine transmissible gastroenteritis coronavirus is a plus-strand, polyadenylylated, infectious RNA molecule of approximately 20 kilobases. During virus replication, seven subgenomic mRNAs are generated by what is thought to be a leader-priming mechanism to form a 3'-coterminal nested set. By using radiolabeled, strand-specific, synthetic oligodeoxynucleotide probes in RNA blot hybridization analyses, we have found a minus-strand counterpart for the genome and for each subgenomic mRNA species in the cytoplasm of infected cells. Subgenomic minus strands were found to be components of double-stranded replicative forms and in numbers that surpass full-length antigenome. We propose that subgenomic mRNA replication, in addition to leader-primed transcription, is a significant mechanism of mRNA synthesis and that it functions to amplify mRNAs. It is a mechanism of amplification that has not been described for any other group of RNA viruses. Subgenomic replicons may also function in a manner similar to genomes of defective interfering viruses to lead to the establishment of persistent infections, a universal property of coronaviruses. .A Sethna PB; Hung SL; Brian DA. .I 125571 .U 89315855 .S Proc Natl Acad Sci U S A 8910; 86(14):5651-5 .M Aging; Amino Acid Sequence; Animal; Base Sequence; Blotting, Northern; Brain/DE/*GD/ME; Cerebellar Diseases/CI/*ME; Cerebellum/*ME; Cloning, Molecular; Gene Expression Regulation/*; Genes, Structural/*; Harmaline/PD; Male; Methylazoxymethanol Acetate/TO; Mice; Mice, Mutant Strains; Molecular Sequence Data; Mutation/*; Nerve Tissue Proteins/*GE; Pyridines/PD; Rats; Rats, Inbred Strains; Reference Values; RNA, Messenger/GE; Transcription, Genetic/*/DE. .T Molecular cloning of a neuron-specific transcript and its regulation during normal and aberrant cerebellar development. .P JOURNAL ARTICLE. .W PEP-19 is a brain-specific polypeptide whose levels increase dramatically during the late maturation of the rodent nervous system. By using immunocytochemistry, PEP-19 is shown to be localized to several regions of the central nervous system, notably cerebellum, thalamus caudate putamen, and olfactory bulb. We have isolated a 0.5-kilobase cDNA clone that encodes the entire PEP-19 protein sequence, making this one of the smallest primary transcripts and translation products ever identified in eukaryotes. The cDNA was used to investigate the developmental expression of PEP-19 in rodent brain. PEP-19 mRNA rises from low levels at embryonic day 17 of gestation in the rat to a plateau value by day 18 postpartum. This mirrored the levels of the protein determined by radioimmunoassay. Since the rise coincided with the formation of synaptic contacts onto Purkinje cells (a major site of PEP-19 expression), the hypothesis was tested that the activity and/or presence of afferent input modulated PEP-19 expression. Parallel fiber innervation was disrupted either by killing granule cells with the cytostatic agent methylazoxymethanol or by examining PEP-19 levels in cerebellar granuloprival mutant mice (reeler and weaver). The influence of climbing fiber input was assessed by either eliminating them with 3-acetylpyridine or stimulating them with harmaline in both neonatal and mature rats. None of the above altered PEP-19 gene expression in cerebellum, leading us to propose that the signals triggering the PEP-19 gene do not emanate from granule cells or neurons in the olivary nucleus. However, preliminary evidence suggests that PEP-19 is under posttranscriptional regulation. .A Sangameswaran L; Hempstead J; Morgan JI. .I 125572 .U 89315856 .S Proc Natl Acad Sci U S A 8910; 86(14):5656-60 .M Adenosine Triphosphate/*PH; Animal; Cerebral Cortex/PH; Dinitrophenols/PD; Electrophysiology; Fluorescent Dyes; Ganglia/PH; In Vitro; Rats; Squid; Support, U.S. Gov't, Non-P.H.S.; Synapses/DE/*PH; Synaptic Vesicles/DE/*PH; Synaptosomes/PH; Xanthenes. .T ATP-dependent directional movement of rat synaptic vesicles injected into the presynaptic terminal of squid giant synapse. .P JOURNAL ARTICLE. .W The question as to whether synaptic vesicles prepared from vertebrate brain can be transported to the active zones of the squid giant synapse was studied by using a combined optical and electrophysiological approach. In order to visualize the behavior of the vertebrate synaptic vesicles in situ, synaptic vesicles isolated from rat brain were labeled with a fluorescent dye (Texas red) and injected into the presynaptic terminal of the squid giant synapse. The pattern of fluorescence that would result from passive diffusion was determined by coinjection of an unconjugated fluorescent dye (fluorescein). The patterns obtained with fluorescent synaptic vesicles were strikingly different from that obtained by simple diffusion of fluorescein. Although the fluorescein diffused freely in both directions, the vesicles moved preferentially into the terminal--i.e., toward the release sites--at a rate of 0.5 microns/sec. The final distribution of the injected fluorescent synaptic vesicles displayed a discrete localization that suggested a distribution coincident with the active zones of the presynaptic terminal. Like fast axonal transport, but unlike fluorescein movements in the terminal, the vesicle movement was energy dependent, since the addition of 2,4-dinitrophenol blocked the redistribution of vesicles completely. In addition, reduction of extracellular calcium concentration reversibly blocked vesicular movement as well. In conclusion, mammalian synaptic vesicles retain the cytoplasmic surface components necessary for translocation, sorting, and targeting to the proper locations by the native machinery of the squid giant synapse. .A Llinas R; Sugimori M; Lin JW; Leopold PL; Brady ST. .I 125573 .U 89315858 .S Proc Natl Acad Sci U S A 8910; 86(14):5666-9 .M Animal; Body Temperature/DE; Brain/DE/*PH; Circadian Rhythm/DE; Dinoprostone/PD/*PH; Male; Prostaglandin Antagonists/*PD; Rats; Rats, Inbred Strains; Reference Values; Sleep/DE/*PH; Sleep, REM/PH; Wakefulness/DE/*PH; Xanthenes/*PD. .T Evidence that brain prostaglandin E2 is involved in physiological sleep-wake regulation in rats. .P JOURNAL ARTICLE. .W We reported in previous studies that prostaglandin E2 (PGE2) has central effects of augmenting wakefulness and suppressing slow-wave sleep (SWS) and paradoxical sleep (PS) in rats. In the present study, we tested the effect of AH 6809, an antagonist of PGE2 receptors, on sleep-wake activities. AH 6809 in saline was infused continuously into the third ventricle of freely moving rats at a rate of 2.1, 6.3, and 21 pmol/min from 2300 to 0500 hr. During the infusion at 21 pmol/min, wakefulness decreased to 82%, and SWS and PS increased to 122% and 161%, of the respective baseline values. These changes can be explained by AH 6809 antagonizing the endogenous PGE2 that acts to augment wakefulness in the brain. This explanation is supported by the fact that the infusion of AH 6809 at 21 pmol/min inhibited the wakefulness-promoting effect of PGE2 infused at 10 pmol/min. Moreover, the PGE2-related mechanisms for regulating sleep-wake activities may be different from those producing hyperthermia, because AH 6809 at 21 pmol/min had no primary effect on brain temperature and did not antagonize the hyperthermia produced by the PGE2 infusion. A diurnal infusion (1200 to 1800 hr) of AH 6809 at 21 pmol/min produced similar effects on sleep-wake activities compared with the nocturnal infusion (2300 to 0500 hr), although the PS increase was not significant, suggesting that the PGE2-related mechanisms are acting all day long with or without a circadian rhythm. These findings strongly suggest that endogenous PGE2 in the brain is involved in the physiological mechanisms for regulating sleep-wake activities. .A Matsumura H; Honda K; Choi WS; Inoue S; Sakai T; Hayaishi O. .I 125574 .U 89316038 .S Phys Ther 8910; 69(8):633-9 .M Adolescence; Bronchi/*; Child; Combined Modality Therapy; Cystic Fibrosis/*TH; Drainage/*MT; Exercise Test; Exercise Therapy/*; Human; Oximetry; Respiratory Function Tests; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Relative effects of bronchial drainage and exercise for in-hospital care of patients with cystic fibrosis. .P JOURNAL ARTICLE. .W Bronchial hygiene therapy is a standard part of the treatment of patients with cystic fibrosis (CF). Coughing alone promotes sputum expectoration and is probably the primary effective component of standard bronchial hygiene therapy. The purpose of this study was to determine whether substituting regular exercise, which also promotes coughing, for two of three daily bronchial hygiene treatments would affect the expected improvements in pulmonary function and exercise response in hospitalized patients with CF. Seventeen patients with CF hospitalized (means length of stay = 13.0 +/- 2.6 days) for an acute exacerbation of their pulmonary disease participated in the study. The patients were randomly assigned to either a group that participated in two cycle ergometer exercise sessions and one bronchial hygiene treatment session per day (EX Group [n = 9]) or a group that participated in three bronchial hygiene treatment sessions per day (PD Group [n = 8]). Pulmonary functions and responses to a progressive, incremental cycle ergometer exercise test were measured on admission and before discharge. Bronchial hygiene therapy consisted of postural drainage, in six positions, with chest percussion and vibration. Therapeutic exercise was of moderate intensity and was individually adjusted based on the patient's heart rate and arterial oxygen saturation response to the admission exercise test. Coughing was encouraged during and after all treatments. Pulmonary function and exercise response were significantly improved over the period of hospitalization in both groups; the improvements were the same in the two groups. These results indicate that, in some hospitalized patients with CF, exercise therapy may be substituted for at least part of the standard protocol of bronchial hygiene therapy. .A Cerny FJ. .I 125575 .U 89316039 .S Phys Ther 8910; 69(8):640-50 .M Adult; Ankle Joint/*PH; Biomechanics; Dominance, Cerebral/*; Female; Gait/*; Human; Knee Joint/*PH; Male; Middle Age. .T Bilateral analysis of the knee and ankle during gait: an examination of the relationship between lateral dominance and symmetry. .P JOURNAL ARTICLE. .W This study examined the relationship between lower extremity dominance and kinematic symmetry during gait. Fourteen healthy volunteers without any observable gait deviations participated in the study. The subjects (8 male, 6 female) ranged in age from 19 to 56 years. Lower extremity lateral dominance was determined using an assessment method developed by Carol Coogler. Retroreflective spherical markers were placed bilaterally at points over the greater trochanter, the lateral joint line of the knee, the lateral malleolus, and the metatarsal break. A video-based data-acquisition instrument interfaced with a PDP 11/73 computer measured 12 kinematic variables while the subjects walked at self-selected speeds along a 10-m walkway. A multivariate analysis of variance with one repeated measure revealed significant differences between limbs, across subjects, for stance time and maximum knee extension. A within-subject analysis demonstrated significant differences for 10 variables; however, lateral dominance could not be related predictably to these variations. Our results indicate that symmetry cannot be generalized in view of intrasubject variability for these variables. [Valle DR, Gundersen LA, Barr AE, et al: Bilateral analysis of the knee and ankle during gait: An examination of the relationship between lateral dominance and symmetry. .A Gundersen LA; Valle DR; Barr AE; Danoff JV; Stanhope SJ; Snyder-Mackler L. .I 125576 .U 89316041 .S Phys Ther 8910; 69(8):656-62 .M Adolescence; Biomechanics; Cerebral Palsy/*PP; Child; Contracture/PP; Female; Gait/*; Hemiplegia/PP; Human; Locomotion; Male; Muscle Contraction; Photogrammetry/MT. .T Toe-walking in children with cerebral palsy: contributions of contracture and excessive contraction of triceps surae muscle. .P JOURNAL ARTICLE. .W The study was designed to provide a quantitative analysis of toe-walking in children with cerebral palsy (CP). The total internal moment developed about the ankle joint during locomotion and the passive component of this internal moment were measured. The contributions of the active and passive components were expressed as the ratio (R) between the passive moment and the total internal moment. Measurements were compared for 13 children with CP and 5 healthy children. For the data analysis, the children with CP, exhibiting apparently similar toe-walking, were divided into two groups: 1) Group CPI and 2) Group CPII. Group CPI was characterized by a small ratio R value, which indicated the presence of excessive contractions of the triceps surae muscle during locomotion. In Group CPII, the ratio R value was abnormally high, which indicated that a contracture (ie, structural change of the muscle or the tendon) was entirely or at least partly responsible for toe-walking. Each group requires a different therapeutic strategy. .A Tardieu C; Lespargot A; Tabary C; Bret MD. .I 125577 .U 89316042 .S Phys Ther 8910; 69(8):663-70 .M Adult; Biomechanics; Female; Gait/*; Heel/*PP; Human; Leg Length Inequality/*PP; Locomotion; Male; Middle Age; Support, Non-U.S. Gov't. .T Effect of heel lifts on ground reaction force patterns in subjects with structural leg-length discrepancies. .P JOURNAL ARTICLE. .W The purpose of this study was to determine the effect of heel lifts on ground reaction force patterns in subjects with structural leg-length discrepancies (LLDs). Eighteen subjects with LLDs ranging from 4.8 to 22.2 mm participated in this study. Subject age range was from 20 to 63 years. A force platform was used to obtain ground reaction force data for four conditions. Data were collected prior to fitting of the heel lift and after a three-week break-in period. Data were analyzed by use of a two-factor within-subject analysis of variance for repeated measures. Before heel-lift fitting, maximum lateral force was greater in the short leg than in the long leg. After heel-lift fitting, maximum vertical force was greater within both legs, and maximum medical force was greater in the long leg than in the short leg. The results suggest that although heel lifts are used to achieve pelvic levelness, the use of heel lifts also resulted in increased ground reaction forces, which may cause increased joint stresses within the lower extremities. .A Schuit D; Adrian M; Pidcoe P. .I 125578 .U 89316044 .S Phys Ther 8910; 69(8):679-89 .M Human; Infrared Rays; Movement/*; Optics; Physical Medicine/*IS/MT; Robotics. .T Reliability and validity of the WATSMART three-dimensional optoelectric motion analysis system. .P JOURNAL ARTICLE. .W Reliability and validity of the WATSMART (Waterloo Spatial Motion Analysis Recording Technique) system was evaluated under static and dynamic conditions. In experiment 1, infrared light-emitting diodes (IREDs) were placed at the axis and along the arms of a clinical goniometer. Twelve angles in 5-degree increments were each recorded 10 times at each of three spatial locations. Reliability was assessed using intraclass correlation coefficients (ICCs) and analysis-of-variance procedures to determine within-trial variability. The ICCs for all spatial locations exceeded .99. The 95% confidence interval for each angle was less than 0.5 degree in all cases. Criterion-referenced instrument validity was assessed with regression analysis. Slopes of the regression of reconstructed angle on reference angle were close to unity for each spatial location. A systematic error, however, that increased as the goniometer was rotated 45 degrees away from the cameras was evident. In experiment 2, a robotic arm was fitted with four IREDs and made to repeat a defined movement trajectory 10 times at each of three spatial locations. The ICCs for portions of each trajectory ranged from .20 to .99. The results show that reliable and valid results can be obtained from this motion analysis system if adequate precautions are taken to reduce unwanted light reflections. Reliability and validity decreased somewhat as the object was rotated further away from the plane in which the cameras were mounted. .A Scholz JP. .I 125579 .U 89316046 .S Phys Ther 8910; 69(8):695-8; discussion 698-9 .M Exercise Therapy/*MT; Human; Muscle Contraction; Poliomyelitis/PP/*RH; Syndrome. .T A rejoinder to "Exercise Programs for Patients with Post-Polio Syndrome: a case report"--a short communication [comment] .P COMMENT; JOURNAL ARTICLE. .W This communication is in response to the article by Michael T Gross and Charles P Schuch entitled "Exercise Programs for Patients with Post-Polio Syndrome: A Case Report" published in the January 1989 issue of Physical Therapy. The investigators examined the effects of a rigorous isokinetic training program on peak torque of the knee flexor and extensor muscles of a post-polio patient. The literature on post-polio syndrome, however, does not support the use of either conventional muscle strengthening regimens or rigorous isokinetic exercise programs in the management of post-polio syndrome. In addition, based on the observation that there was no appreciable increase in muscle strength in either the affected or the apparently unaffected leg, the investigators concluded that their rigorous exercise program was not deleterious. The lack of a normal training response, however, is consistent with bilateral muscle fatigue secondary to overuse rather than muscle weakness secondary to disuse. This result is consistent with the need for a balance between rest and low-intensity exercise, which will help to maintain or enhance function while slowing rather than hastening further deterioration. We hope that this rejoinder clarifies some of the misconceptions that may arise from the Gross and Schuch article and that physical therapists consider very carefully the rationale for any type of exercise program for post-polio patients. .A Dean E; Ross J; MacIntyre D. .I 125580 .U 89316047 .S Phys Ther 8910; 69(8):700-2 .M Human; Physical Therapy/*MT; Reproducibility of Results; Statistics/*ST. .T Not really reliability? [letter; comment] .P COMMENT; LETTER. .A Stratford PW. .I 125581 .U 89316048 .S Phys Ther 8910; 69(8):702 .M Education, Continuing/*; Human; Physical Therapy/ED/*OG; Societies; United States. .T Section educational opportunities [letter; comment] .P COMMENT; LETTER. .A Johnson GR. .I 125582 .U 89316067 .S Plast Reconstr Surg 8910; 84(2):189-202 .M Cartilage/*TR; Female; Human; Male; Methods; Nasal Septum/BS/SU; Nose/BS/*SU; Nose Neoplasms/SU; Surgical Flaps/*. .T Nasal support and lining: the marriage of beauty and blood supply. .P JOURNAL ARTICLE. .W Assured of a robust blood supply by its narrow pedicle centered on the septal branch of the superior labial artery, the pivoting septal flap provides nasal support from the radix to the most distal nasal tip and from the tip to the columella base--plus a large bonus of lining tissues for the nasal vault and vestibules. Lining flaps from such intranasal tissues are thin, vascular, and flexible. They allow the use of primary cartilage grafts and the establishment of a subsurface architecture in the shape of a nose. When visualized through a conforming forehead flap, the normal landmarks and highlights are restored. In cases of total nasal amputation, a pivoting septal flap permits the fabrication of dorsal nasal support weeks before lining and cover flaps are assembled. .A Burget GC; Menick FJ. .I 125583 .U 89316068 .S Plast Reconstr Surg 8910; 84(2):204-12 .M Adult; Audio-Visual Aids; Case Report; Female; Human; Medical Records; Middle Age; Photography; Rhinoplasty/ED/*MT. .T A graphic record of intraoperative maneuvers in rhinoplasty: the missing link for evaluating rhinoplasty results. .P JOURNAL ARTICLE. .W A pictorial system is introduced for documenting intraoperative maneuvers in rhinoplasty that can be used to advantage for relating the effect that different surgical techniques have on postoperative results and for describing to other surgeons the technical steps performed in the operation. .A Gunter JP. .I 125584 .U 89316069 .S Plast Reconstr Surg 8910; 84(2):213-6; discussion 217-8 .M Child, Preschool; Human; Orbital Fractures/*PA/RA/SU; Skull Fractures/*PA; Tomography, X-Ray Computed. .T Orbital roof fractures in the pediatric population. .P JOURNAL ARTICLE. .W Twenty-three patients aged 3.3 +/- 1.6 years (mean +/- SD) presented between January of 1984 and September of 1987 with fronto-orbital trauma resulting in fractures of one (N = 20) or both (N = 3) orbital roofs. All patients had computed tomography (CT) with axial and coronal sections that revealed three fracture patterns of the orbital roof (nondisplaced, superiorly displaced, and inferiorly displaced fractures). Orbital dystopia was exhibited in 35 percent (N = 8) of the patients. Exophthalmos was noted in 61 percent (N = 14) of the patients. Only 30 percent of the patients (N = 7) sustained associated maxillofacial fractures. Eight percent of fractures exhibited orbital encephaloceles. All patients lacked frontal sinus pneumatization. The majority of children with orbital roof fractures do not exhibit concomitant facial fractures. CT utilizing both axial and coronal sections is valuable in defining the extent and pattern of the fracture as well as in identifying associated neurologic injuries. Large, displaced orbital roof fractures, which occurred in 3 of 13 patients with displaced fractures in our series, should undergo early reduction to avoid late development of encephalocele. .A Messinger A; Radkowski MA; Greenwald MJ; Pensler JM. .I 125585 .U 89316070 .S Plast Reconstr Surg 8910; 84(2):219-26 .M Case Report; Child, Preschool; Diagnosis, Differential; Female; Hand Deformities, Congenital/PA; Human; Infant; Infant, Newborn; Male; Mandibulofacial Dysostosis/DI/PA; Palate, Soft/*AB/SU; Syndrome. .T A significant feature of Nager's syndrome: palatal agenesis. .P JOURNAL ARTICLE. .W Nager's syndrome, which has the facial features of Treacher Collins syndrome, preaxial upper limb defects, short stature, and frequently subnormal intelligence, is very rare. Five new cases have been collected. In four, there was virtually total absence of the soft palate. This has been described in two patients in the past. Differing methods of correcting this are presented. .A Jackson IT; Bauer B; Saleh J; Sullivan C; Argenta LC. .I 125586 .U 89316073 .S Plast Reconstr Surg 8910; 84(2):245-9 .M Animal; Bone and Bones/BS/*SU; Hydroxyapatites/*; Implants, Artificial/*; Male; Nasal Bone/SU; Neovascularization/*; Rabbits; Support, Non-U.S. Gov't. .T The rate of vascularization of coralline hydroxyapatite. .P JOURNAL ARTICLE. .W Coralline hydroxyapatite (CHAP) is a porous, biocompatible bone-graft substitute manufactured by the Replamineform process. The use of this material in the experimental and clinical settings for maxillofacial onlay grafting has been recently described. This study was designed to quantitate the rate of vascularization of coralline hydroxyapatite when used in an onlay application to membranous bone in an animal model. Sixteen onlay grafts of coralline hydroxyapatite (0.5 X 0.5 X 1.0 cm Interpore 200) were placed in a subperiosteal location on the nasal dorsum of 2- to 3-kg male New Zealand white rabbits. The grafts and nasal bones were harvested en bloc at 1, 2, 3 and 4 weeks after onlay. Prior to harvest, injectable silicone visualizing agent (Microfil*) was injected by means of carotid artery cutdown. The decalcified specimens were examined on a digitizing pad to count the number of vessels appearing in the blocks of hydroxyapatite. Counting was summed and integrated by an Apple IIe microcomputer. A significant difference (p less than 0.05) was noted in both the number of vessels and the fraction of implants infiltrated by vessels between 1 and 4 weeks. The usefulness of these previously undescribed data may be in their extrapolation to onlay grafts of coralline hydroxyapatite in maxillofacial reconstruction in humans. .A Grenga TE; Zins JE; Bauer TW. .I 125587 .U 89316074 .S Plast Reconstr Surg 8910; 84(2):250-7 .M Cleft Palate/SU; Facial Muscles/AH/BS/SU; Fistula/SU; Human; Mandibular Diseases/SU; Methods; Mouth/*SU; Osteitis/SU; Palatal Neoplasms/SU; Surgical Flaps/*. .T The buccinator musculomucosal flap: anatomic study and clinical application. .P JOURNAL ARTICLE. .W Since 1984, we have used the buccinator muscle mucosal flap for the treatment of mucosal defects after tumor resection, osteomyelitis of the mandible, closure of cleft palate fistulas, primary closure of very wide cleft palates, and lengthening of the soft palate. A study was made in the facial regions of 14 cadavers, and a comparison was made to descriptions found in the anatomic literature. It was confirmed in our dissections that the buccal artery, which reaches the posterior half of the muscle, is the major arterial pedicle of the buccinator and that it runs very close to the buccal nerve. Several veins originating from the lateral aspect of the muscle make the venous drainage of the buccinator even richer than its arterial supply. The abundant vascular supply from multiple interconnected pedicles supports the blood supply of the buccal mucosa. The motor innervation of the buccinator muscle comes from the facial nerve. The buccinator is considered to be a part of the sphincteric muscular system involving the functions of sucking, whistling, propelling food during mastication, and voiding the buccal cavity. The flap was utilized clinically in 38 patients: 24 to close primary cleft palates that required palate lengthening, 12 to close palatal fistulas, 1 to treat a mandibular osteitis, and 1 to repair the palate after tumor resection. We had three small fistulas as complications in our series owing to technical mistakes. .A Bozola AR; Gasques JA; Carriquiry CE; Cardoso de Oliveira M. .I 125588 .U 89316075 .S Plast Reconstr Surg 8910; 84(2):258-64; discussion 265-6 .M Adult; Aged; Breast/BS/*PA/SU; Female; Human; Mastectomy, Subcutaneous/*AE; Methods; Middle Age; Necrosis; Nipples/BS/*PA; Skin/BS/PA. .T Conservative management in full-thickness nipple-areolar necrosis after subcutaneous mastectomy [see comments] .P JOURNAL ARTICLE. .W Nipple-areolar necrosis is a known and expected complication in a small percentage of patients undergoing subcutaneous mastectomy, especially with concomitant mastopexy or in smokers. Impending ischemia or congestion of the areola can often be ameliorated by simple maneuvers such as suture release. When full-thickness necrosis occurs, conservative management with essential debridement, dressings, and careful wound hygiene alone will often yield a surprisingly good result, requiring little or no revisional surgery. .A Woods JE; Meland NB. .I 125589 .U 89316077 .S Plast Reconstr Surg 8910; 84(2):273-9 .M Adolescence; Adult; Child; Child, Preschool; Female; Hemangioma/SU; Human; Infant; Laser Surgery/*/IS/MT; Lymphangioma/SU; Male; Neoplasms, Vascular Tissue/*SU; Neurofibroma/SU; Postoperative Complications. .T Sapphire tip technology for YAG laser excisions in plastic surgery. .P JOURNAL ARTICLE. .W Thirty-two patients with a variety of vascular and nonvascular lesions have been resected over a 3-year period with the neodymium:YAG laser utilizing sapphire peripheral scalpel devices. These innovative peripheral devices concentrate the YAG laser energy to a small area at the end of the scalpel, providing precise incisions with excellent hemostasis. In addition, the tactile sensation of the scalpel contacting tissue is more comfortable and familiar than the "no touch" aspect of other lasers that are held away from the surface and depend on laser light transmission to approach the skin. Total excision with excellent hemostasis was achieved in 17 patients, while 15 patients had subtotal resection. The YAG laser with sapphire scalpels has allowed resection of very difficult and massive hemangiomas previously considered unresectable by standard techniques. .A Apfelberg DB; Maser MR; Lash H; White DN. .I 125590 .U 89316078 .S Plast Reconstr Surg 8910; 84(2):280-8; discussion 289 .M Animal; Arteriovenous Anastomosis/*; Embolism/ET/PA/*PP; Groin; Microcirculation/PA/PP; Muscles/BS; Postoperative Complications/*; Rats; Rats, Inbred Strains; Video Recording. .T Direct in vivo observations of embolic events in the microcirculation distal to a small-vessel anastomosis. .P JOURNAL ARTICLE. .W This study was done to determine whether microemboli are produced by an arterial anastomosis. Direct in vivo observations were made in an isolated microcirculatory bed lying directly downstream from a newly made anastomosis. The tissue used was the isolated rat cremaster muscle, a new experimental model. The vessel anastomosed was the external iliac artery. Following anastomosis, microemboli were clearly observed in eight of eight animals during the first 30 minutes after clamp release. Embolic events were sometimes of impressive magnitude and in one case were associated with cessation of blood flow throughout the preparation. No microemboli were observed in eight of eight animals subjected only to dissection of the cremaster, nor were any observed in eight of eight animals in which the isolated cremaster was subjected only to 2 hours of clamp ischemia. These findings may be significant in explaining perturbations to blood flow following free-tissue transfer and instances of partial tissue necrosis following apparently successful arterial repair. These findings also identify an important factor (microemboli) to be considered in research on reperfusion injury. .A Acland RD; Anderson G; Siemionow M; McCabe S. .I 125591 .U 89316079 .S Plast Reconstr Surg 8910; 84(2):290-5 .M Adult; Aged; Case Report; Extremities/SU; Female; Head and Neck Neoplasms/SU; Human; Male; Methods; Surgical Flaps/*. .T The "reduced" latissimus dorsi musculocutaneous flap. .P JOURNAL ARTICLE. .W This report introduces a new device among latissimus dorsi flaps: the "reduced" latissimus dorsi musculocutaneous flap. This flap consists of a proximal musculocutaneous unit and a distal, thin fasciocutaneous unit (the "reduced" portion). The former unit carries a reliable blood supply from the thoracodorsal artery and is able to cover deeper recipient defects, while the latter provides a well-contoured reconstruction of the defect. If needed, an extended portion and/or a thin cutaneous flap can be carried along with the flap according to the defect. In our clinic, we have so far used four pedicled and one free reduced latissimus dorsi musculocutaneous flap in the repair of a variety of defects. All flaps survived, and satisfactory contour of the recipient site was achieved in each case. These clinical experiences clarify that a reduced portion 10 cm in length can be safely carried, and it is suggested that survival of this flap does not depend on its width-to-length ratio. .A Hayashi A; Maruyama Y. .I 125592 .U 89316080 .S Plast Reconstr Surg 8910; 84(2):296-302 .M Case Report; Decubitus Ulcer/SU; Human; Male; Methods; Middle Age; Reoperation; Surgical Flaps/*; Thigh. .T Multiple and repetitive uses of the extended hamstring V-Y myocutaneous flap. .P JOURNAL ARTICLE. .W An extended hamstring V-Y myocutaneous advancement flap is described that may be used to cover unusually large defects in the ischial region. Technical points that allow a large amount of flap advancement are discussed. Because of its large size, the flap can be raised and used on repeated occasions to repair defects from recurrent ischial pressure sores. Two patients are presented in whom the same flap was used repeatedly on multiple occasions, demonstrating the potential for preservation of future options in such patients when this flap is used. .A Kroll SS; Hamilton S. .I 125593 .U 89316082 .S Plast Reconstr Surg 8910; 84(2):314-22; discussion 323-4 .M Animal; Capillaries/PH; Implants, Artificial/*; Male; Regional Blood Flow; Skin/*BS; Support, Non-U.S. Gov't; Surgical Flaps/*; Swine. .T Effect of capsulectomy on the hemodynamics and viability of random-pattern skin flaps raised on expanded skin in the pig. .P JOURNAL ARTICLE. .W Skin flaps constructed on expanded skin usually include the underlying capsular tissue. It has been hypothesized that capsulectomy may jeopardize the viability of the expanded skin flap. The experiments reported herein were designed to test this hypothesis. Specifically, we studied the hemodynamics and viability of random-pattern skin flaps (8 X 20 cm) raised on delayed bipedicle flaps (group A) and on expanded skin pockets with capsulectomy at the time of flap elevation (group B) or with intact underlying capsular tissue (group C). Each group was randomly assigned to each flank in 16 pigs. Skin pockets were expanded by inflation of subcutaneous silicone tissue expanders with sterile saline (299 +/- 7 ml; X +/- SEM) over a period of 3 weeks. At the end of this period, the bipedicle flaps were constructed. Eight days later, random-pattern skin flaps were raised on bipedicle flaps and skin pockets. The length and area of skin flap viability, judged by the fluorescein dye test performed 1 day postoperatively, were not significantly different (p greater than 0.05) among groups A, B, and C (n = 31 to 32). There also were no significant differences (p greater than 0.05) in total skin capillary blood flow measured 1 day postoperatively (A = 2.6 +/- 0.4, B = 2.4 +/- 0.4, and C = 2.7 +/- 0.6 ml/min per flap; n = 15 to 16) and in skin viability assessed 7 days postoperatively (A = 74 +/- 2, B = 75 +/- 2, and C = 76 +/- 2 percent; n = 16) among delayed skin flaps and skin flaps raised on expanded skin pockets with or without capsulectomy. The results of this flap viability study were confirmed in 5 minipigs in a separate experiment. We conclude that capsulectomy did not have a detrimental effect on the hemodynamics and viability of random-pattern skin flaps raised on expanded skin. Furthermore, we hypothesize that skin flaps raised on expanded skin are similar to delayed skin flaps in that the skin blood flow is optimally augmented; therefore, the capsular tissue does not add significant blood supply to the overlying skin. .A Morris SF; Pang CY; Mahoney J; Lofchy N; Kaddoura IL; Patterson R; Lista F. .I 125594 .U 89316083 .S Plast Reconstr Surg 8910; 84(2):325-37 .M Adrenal Hyperplasia, Congenital/*SU; Child; Child, Preschool; Female; Follow-Up Studies; Genitalia/AB/*SU; Human; Infant; Surgery, Plastic/*MT. .T Reconstruction of the external genitalia in the adrenogenital syndrome by means of a personal one-stage procedure [see comments] .P JOURNAL ARTICLE. .W The techniques for correction of the external genitalia in the adrenogenital syndrome, as far as known by the author, are reviewed. The goals of repair and timing of surgery are discussed. The author's one-stage technique, first published in 1974, is described with intraoperative illustrations, and the results obtained in nine patients are discussed. The advantages of the technique are preservation of a clitoral glans with erogenous sensation based exclusively on the deep dorsal neurovascular bundle. The glans of the megaloclitoris is obliquely reduced in size at its base toward the ventral surface and by resection of up to two-thirds of the ventral segment. It is relocated at its anatomic female position. The labia minora and the introitus vaginae are reconstructed at the same stage with the skin of the megaloclitoris displaced in posterior direction after a cutback incision. Dispareunia is prevented by total excision of the corpora cavernosa, including the crura. .A Hinderer UT. .I 125595 .U 89316084 .S Plast Reconstr Surg 8910; 84(2):338-9 .M Medical Records/*. .T Weighty records: medicine by bulk [editorial] .P EDITORIAL. .A Goldwyn RM. .I 125596 .U 89316085 .S Plast Reconstr Surg 8910; 84(2):340-1 .M Ethics, Medical/*; Human; Malpractice/*; Surgery, Plastic/*. .T Have we really come this far?[editorial] .P EDITORIAL. .A Curtin JW. .I 125597 .U 89316086 .S Plast Reconstr Surg 8910; 84(2):342-6 .M Adult; Case Report; Female; Head and Neck Neoplasms/SU; Human; Methods; Neoplasm Recurrence, Local/SU; Reoperation; Surgical Flaps/*; Trachea/*SU. .T Reconstruction of the mediastinal trachea with a tubed pectoralis major myocutaneous flap. .P JOURNAL ARTICLE. .W A young patient with a massive postirradiation recurrence of thyroid cancer invading the larynx and mediastinal trachea had been treated by resecting the larynx and trachea to within three rings of the carina. A mediastinal tracheostomy was avoided by using a tubed pectoralis major myocutaneous flap to replace the ablated trachea. The flap, transferred into the mediastinum subclavicularly, was connected to the tracheal stump and exteriorized as a cervical tracheostomy. This resulted in direct closure of the donor site and primary healing. Four years after the operation, the patient remains free of disease and is tolerating the neotrachea without difficulty or complications. The technique described is offered as an alternative to conventional mediastinal tracheostomy methods, which have acknowledged shortcomings. .A Fleischer A; Khafif R. .I 125598 .U 89316087 .S Plast Reconstr Surg 8910; 84(2):347-52 .M Abdominal Wall/*AB/SU; Female; Human; Implants, Artificial/*; Infant; Methods. .T Abdominal wall expansion in congenital defects. .P JOURNAL ARTICLE. .W A method for expanding the skin, fascia, muscle, and peritoneal layers of the abdominal wall is described, and clinical application is demonstrated in two children with cloacal exstrophy and congenital absence of the lower half of the abdominal wall. This technique provides an innervated composite reconstruction of defects in excess of 50 percent of the abdominal surface and is recommended in large secondary defects where peritonealization has been achieved and in congenital defects that do not lend themselves to standard methods of closure. Cadaver dissection confirms that tissue expanders may be placed with preservation of innervation and blood supply to the abdominal wall. .A Byrd HS; Hobar PC. .I 125599 .U 89316088 .S Plast Reconstr Surg 8910; 84(2):353-5 .M Botulinum Toxins/*TU; Case Report; Facial Asymmetry/ET/*TH; Facial Paralysis/*CO; Female; Human; Middle Age; Rhytidoplasty/AE. .T Botulinum toxin: a treatment for facial asymmetry caused by facial nerve paralysis. .P JOURNAL ARTICLE. .W Injury to the frontal or other facial nerve branches can result in an asymmetry that can be very distressful to both patient and surgeon. This is especially true following cosmetic procedures such as rhytidectomy. We propose a means to create temporary symmetry while awaiting the possible return of nerve function. Botulinum neurotoxin causes a muscle paralysis lasting for approximately 3 months, and it is well established as the preferred treatment for blepharospasm. A case is presented in which botulinum toxin type A was injected into the opposite functioning frontalis muscle of a patient with unilateral frontal nerve paralysis. The patient experienced satisfactory relief of the asymmetry caused by onesided forehead wrinkling and brow elevation. Botulinum toxin therapy should be considered for both temporary and permanent facial asymmetries due to facial nerve paralysis as well as spasm. .A Clark RP; Berris CE. .I 125600 .U 89316090 .S Plast Reconstr Surg 8910; 84(2):363-4 .M Human; Nicaragua; Surgery, Plastic/*. .T Reconstructive surgery in Nicaragua [letter; comment] .P COMMENT; LETTER. .A Lineaweaver WC. .I 125601 .U 89316091 .S Plast Reconstr Surg 8910; 84(2):364 .M Photography/*IS; Surgery, Operative/*. .T A pointer on pointers [letter] .P LETTER. .A Hoehn JG. .I 125602 .U 89316092 .S Plast Reconstr Surg 8910; 84(2):364 .M Human; Methods; Pathology, Surgical/MT; Surgical Flaps/*. .T Measuring the area of a lesion or flap [letter] [see comments] .P LETTER. .A Furnas H. .I 125603 .U 89316093 .S Plast Reconstr Surg 8910; 84(2):364-6 .M Arthritis, Rheumatoid/CI; Case Report; Face/*PA; Female; Human; Inflammation/CI/PA; Injections; Magnetic Resonance Imaging/*; Middle Age; Silicones/AD/*AE; Suction. .T Localization of injected silicone with MRI prior to removal by suction cannula [letter] .P LETTER. .A Bailey MH; Jackson IT; Baker HL; Allen GL. .I 125604 .U 89316094 .S Plast Reconstr Surg 8910; 84(2):366 .M Human; Rhinoplasty/*MT. .T Nasion graft in rhinoplasty [letter; comment] .P COMMENT; LETTER. .A Bortnick E. .I 125605 .U 89316095 .S Plast Reconstr Surg 8910; 84(2):366-7 .M Human; Microsurgery/*IS; Surgery, Plastic/*IS. .T Usefulness of the silicone microsurgical background [letter] .P LETTER. .A Isogai N; Kamiishi H. .I 125606 .U 89316096 .S Plast Reconstr Surg 8910; 84(2):367-9 .M Human; Methods; Surgical Flaps/*. .T Extracorporeal tissue transfer [letter] .P LETTER. .A Govila A. .I 125607 .U 89316097 .S Plast Reconstr Surg 8910; 84(2):369-70 .M Child, Preschool; Cleft Lip/PP/*SU; Hearing/*; Human; Infant; Methods; Speech Intelligibility/*. .T Improved hearing and improved speech [letter; comment] .P COMMENT; LETTER. .A Dellon AL. .I 125608 .U 89316098 .S Plast Reconstr Surg 8910; 84(2):370 .M Ear, External/*AB/SU; Human; Models, Anatomic/*; Surgery, Plastic/*IS. .T Ear models [letter; comment] .P COMMENT; LETTER. .A Rueckert F. .I 125609 .U 89316099 .S Plast Reconstr Surg 8910; 84(2):370-2 .M Adolescence; Case Report; Fibrous Dysplasia of Bone/SU; Human; Male; Mandibular Diseases/SU; Mandibular Prosthesis/*; Methylmethacrylates/*. .T Prefabricated methyl methacrylate implant for reconstruction of the hemimandible and temporomandibular joint complex [letter] .P LETTER. .A Govila A. .I 125610 .U 89316100 .S Plast Reconstr Surg 8910; 84(2):372 .M Certification/*; Hand/*SU; Surgery, Plastic/*; United States. .T In support of the certificate of added qualifications in hand surgery [letter] .P LETTER. .A McCormack RM. .I 125611 .U 89316101 .S Plast Reconstr Surg 8910; 84(2):372 .M Electrocoagulation/*IS; Human; Laser Surgery/IS; Smoke; Suction/IS; Surgery, Plastic/*; Surgical Equipment/*. .T Using the suction apparatus of the laser machine to get rid of smoke from electrocoagulation [letter] .P LETTER. .A Karaca AR. .I 125612 .U 89316102 .S Plast Reconstr Surg 8910; 84(2):372-3 .M Cleft Lip/CO/*PA/SU; Extraoral Traction Appliances/*; Human; Malocclusion/CO/*TH; Maxilla/*PA; Orthodontic Appliances, Removable/*; Preoperative Care. .T Protruding premaxilla in the bilateral cleft lip patient [letter; comment] .P COMMENT; LETTER. .A Georgiade NG; Mason RM; Riefkohl RE; Georgiade GS; Barwick W. .I 125613 .U 89316103 .S Plast Reconstr Surg 8910; 84(2):373-4 .M Biopsy/*; Disease Susceptibility; Human; Malignant Hyperthermia/*DI; Muscles/*PA. .T Muscle biopsy testing for malignant hyperthermia [letter; comment] .P COMMENT; LETTER. .A Allen G; Rosenberg H. .I 125614 .U 89316105 .S Plast Reconstr Surg 8910; 84(2):375 .M Human; Postoperative Care/*; Pressure; Rhinoplasty/*. .T Postoperative nighttime nasal taping to decrease swelling [letter] .P LETTER. .A Hoefflin SM. .I 125615 .U 89316106 .S Plast Reconstr Surg 8910; 84(2):376 .M Case Report; Choristoma/*CO; Cleft Lip/*CO; Cleft Palate/*CO; Female; Head and Neck Neoplasms/*CO; Human; Infant, Newborn; Thymus Gland/*. .T Bilateral ectopic thymus gland tissue associated with the cleft lip and palate [letter; comment] .P COMMENT; LETTER. .A Dado DV; Gonzalez-Crussi F. .I 125616 .U 89316107 .S Plast Reconstr Surg 8910; 84(2):376-7 .M Abdomen/*SU; Animal; Equipment and Supplies; Rats/*; Research; Surgical Flaps/*. .T Protection of abdominal flaps from self-mutilation in the rat [letter] .P LETTER. .A Tark KC. .I 125617 .U 89316109 .S Prim Care 8910; 16(2):289-550 .M Aged; Geriatrics/*; Human. .T Care of the aging patient. .P JOURNAL ARTICLE. .I 125618 .U 89316287 .S Radiology 8910; 172(2):313-4 .M Human; Lung/RI; Pulmonary Embolism/*RI; Ventilation-Perfusion Ratio. .T Another look at pulmonary embolism [editorial] .P EDITORIAL. .A Alderson PO. .I 125619 .U 89316288 .S Radiology 8910; 172(2):315-7 .M Human; Lymphatic Diseases/DI/RA/RI; Lymphatic System/*RI; Lymphedema/RA/RI; Lymphography/*. .T The lymphatic system: diagnostic imaging studies. .P JOURNAL ARTICLE. .A Weissleder R; Thrall JH. .I 125620 .U 89316289 .S Radiology 8910; 172(2):318-20 .M Brain/PA; Brain Neoplasms/DI; Human; Nuclear Magnetic Resonance/*DU/MT; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.. .T The power of the proton [editorial; comment] .P COMMENT; EDITORIAL. .A Weiner MW; Hetherington HP. .I 125621 .U 89316291 .S Radiology 8910; 172(2):327-30 .M Adult; Aged; Aged, 80 and over; Angiography; Angioplasty, Transluminal/AE/*MT; Arterial Occlusive Diseases/RA/*TH; Chronic Disease; Female; Human; Leg/*BS; Male; Middle Age. .T Low-speed rotational angioplasty in chronic peripheral artery occlusions: experience in 83 patients. Work in progress. .P JOURNAL ARTICLE. .W Between December 1986 and October 1988, 83 patients with chronic peripheral artery occlusions were treated with a new technique. In 56 patients, the superficial femoral artery was completely occluded; in 21 patients, the popliteal artery; and in six patients, the iliac artery. The length of occlusion ranged from 5 to 35 cm (mean, 12.5 cm). The duration, estimated by history, was 5-48 months (mean, 16.5 months). In seven patients, durations of 6-36 months were documented angiographically. A flexible, blunt, motor-driven rotating catheter was introduced through an 8-F sheath, and rotational angioplasty was performed at low speed (up to 200 rpm). In 49 of 60 (82%) patients in whom this new technique was used as the primary intervention, the occlusions were successfully reopened. In 23 patients in whom conventional methods had failed more than 4 weeks earlier, the success rate for rotational angioplasty was 67% (12 of 18 patients); when the time interval was less than 4 weeks, only one of five patients was treated successfully. In none of the 83 patients did a perforation occur. This new technique can reopen chronic artery occlusions with a high degree of success and without the danger of vessel-wall perforation, even after failure of conventional techniques. .A Vallbracht C; Liermann DD; Prignitz I; Beinborn W; Roth FJ; Kollath J; Landgraf H; Kaltenbach M. .I 125622 .U 89316293 .S Radiology 8910; 172(2):337-9 .M Adult; Aged; Bladder Neoplasms/CO; Embolization, Therapeutic/*/AE/MT; Female; Genital Neoplasms, Female/CO; Hemorrhage/ET/RA/*TH; Human; Iliac Artery/*/RA; Male; Middle Age; Pelvic Neoplasms/*CO; Prostatic Neoplasms/CO. .T Internal iliac artery: embolization to control hemorrhage from pelvic neoplasms. .P JOURNAL ARTICLE. .W The control of the massive and often fatal hemorrhage from pelvic neoplasms is a major therapeutic problem. Transcatheter embolization of the internal iliac arteries was performed in 108 patients with uncontrollable hemorrhage due to pelvic neoplasms (urinary bladder in 50, uterus in 39, ovary in 16, and prostate in three). Complete control of the hemorrhage was achieved in 74 patients, partial control in 23, and no control in 11. Seventy patients experienced postembolization syndrome (nausea, vomiting, gluteal pain, and fever due to tissue necrosis), and three had transient acute tubular necrosis caused by the contrast medium. It is important for success that the embolization be bilateral and that the embolic agent used be a permanent one. .A Pisco JM; Martins JM; Correia MG. .I 125623 .U 89316295 .S Radiology 8910; 172(2):345-8 .M Anticoagulants/*; Blood Coagulation/*DE; Contrast Media/*PD; Diatrizoate/PD; Diatrizoate Meglumine/PD; Human; Iohexol/PD; Iopamidol/PD; Ioxaglic Acid/PD; Support, Non-U.S. Gov't; Thrombin Time; Whole Blood Coagulation Time. .T Differing mechanisms of clotting inhibition by ionic and nonionic contrast agents. .P JOURNAL ARTICLE. .W The anticoagulant potency of ioxaglate has been shown to be approximately twice that of iopamidol and iohexol. Those findings were obtained with use of the thrombin time as a test and platelet-poor plasma as a thrombin substrate. The authors confirmed these findings with use of a whole-blood version of the same test. However, the thrombin time measures only the final stages of the clotting process. A measure of the entire intrinsic pathway would more nearly simulate the situation in the angiographic suite. When measured with such an assay, the anticoagulant potency of ioxaglate was equivalent to that of diatrizoate and was approximately four times that of iopamidol and iohexol. Because of this difference in potency, it seemed likely that the ionic agents were inhibiting the clotting cascade at a late stage as well as at an earlier stage. To investigate this possibility, whole blood-contrast agent mixtures were activated, incubated for several minutes, and then diluted with either citrated or heparinized whole blood. There was rapid clot formation when the unclotted iopamidol and iohexol mixtures were diluted with citrated whole blood but not when they were diluted with heparinized whole blood. The ionic mixtures did not clot in the presence of either anticoagulant. Thus, in unclottable mixtures nonionic agents still permitted the generation of procoagulants. These procoagulants are theoretically capable of causing clotting on reinjection. .A Ing JJ; Smith DC; Bull BS. .I 125624 .U 89316296 .S Radiology 8910; 172(2):349-50 .M Heart/*AH; Human; Magnetic Resonance Imaging/*MT; Movement. .T Heart wall motion: improved method of spatial modulation of magnetization for MR imaging. .P JOURNAL ARTICLE. .W A previously reported method of using magnetic resonance (MR) imaging to study heart wall motion involves a pair of nonselective radio-frequency (RF) pulses, separated by a magnetic field gradient pulse, prior to imaging; this produces images with a regular pattern of stripes that move with the heart wall and that have a sinusoidal intensity profile. It is demonstrated in this study that the substitution of more RF pulses, with their relative amplitudes distributed according to the binomial sequence, results in sharper stripes. This permits the use of a two-dimensional grid of stripes for more detailed studies of heart wall motion and provides a unique method of analyzing regional ventricular myocardial strain. .A Axel L; Dougherty L. .I 125625 .U 89316297 .S Radiology 8910; 172(2):351-7 .M Arteries/*AH/PA; Human; Magnetic Resonance Imaging/*MT; Veins/*AH/PA. .T Projection arteriography and venography: initial clinical results with MR. .P JOURNAL ARTICLE. .W Motion currently limits the applications of magnetic resonance (MR) angiography in certain regions of the body. To overcome this problem, a series of breath-hold, two-dimensional, flow-compensated gradient-echo images were acquired. These images were then processed by means of the maximum intensity projection algorithm to produce projection angiograms. The method was evaluated in 10 healthy subjects and in 12 patients and validated by comparing conventional angiograms, contrast material-enhanced computed tomographic scans, and duplex sonograms with MR projection arteriograms and venograms of the chest, abdomen, and pelvis. The aorta and pulmonary arteries and their branches were demonstrated, as was detailed anatomy of the hepatic and portal venous systems and inferior vena cava. Renal arteries and veins could be studied in both native and transplanted kidneys. The method permits determination of flow direction and differentiation of arteries and veins and is superior to three-dimensional acquisition techniques for imaging slow blood flow. Initial results suggest that the method may have clinical applications for a variety of vascular disorders. .A Edelman RR; Wentz KU; Mattle H; Zhao B; Liu C; Kim D; Laub G. .I 125626 .U 89316298 .S Radiology 8910; 172(2):359-62 .M Adult; Aged; Aged, 80 and over; Aorta, Abdominal/PA/*SU; Blood Vessel Prosthesis/*; Female; Graft Survival; Human; Infection/*DI; Magnetic Resonance Imaging/*; Male; Middle Age; Postoperative Complications/*DI; Retroperitoneal Space; Support, Non-U.S. Gov't; Wound Healing. .T Incorporation versus infection of retroperitoneal aortic grafts: MR imaging features. .P JOURNAL ARTICLE. .W The magnetic resonance (MR) imaging characteristics of normal aortic graft healing were compared with those of perigraft infection in 57 patients after aortic graft implantation. Thirty-three patients without postoperative complications underwent MR imaging in a 0.35-T unit 1 week after graft implantation, and 13 of those patients were reexamined 2-3 months after graft implantation. Twenty-four patients with clinically suspected perigraft infection underwent MR imaging 6 weeks to 18 years after graft implantation. Early normal postoperative changes were characterized by a perigraft collar of low to medium signal intensity on T1-weighted images and of high intensity on T2-weighted images in all 33 cases, consistent with perigraft fluid collection. In 10 of 13 patients reexamined 2-3 months postoperatively, the MR images demonstrated a collar of tissue consistent with perigraft fibrosis. In cases of clinical suspicion of retroperitoneal graft infection, MR imaging showed eccentric fluid collections of low to medium signal intensity on T1-weighted images and high intensity on T2-weighted images at more than 3 months after surgery. The MR findings were diagnostic of retroperitoneal perigraft infection in 17 of 20 patients shown to be infected at surgery. Retroperitoneal infection was correctly excluded on the basis of MR findings in four patients. Thus, MR imaging is an accurate imaging method for the diagnosis of aortic graft infection. In the early postoperative phase, resolving perigraft fluid cannot be differentiated from perigraft infection. .A Auffermann W; Olofsson PA; Rabahie GN; Tavares NJ; Stoney RJ; Higgins CB. .I 125627 .U 89316299 .S Radiology 8910; 172(2):363-6 .M Blood Flow Velocity; Fingers/*BS; Human; Magnetic Resonance Imaging/*MT; Regional Blood Flow; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.. .T Use of radio-frequency field gradients to image blood flow and perfusion in vivo. .P JOURNAL ARTICLE. .W A magnetic resonance imaging method based on the use of radio-frequency (RF) magnetic field gradients to detect molecular motion has been combined with GRASS (gradient-recalled acquisition in a steady state) imaging to detect arterial blood flow in vivo. The method has been used to selectively attenuate signals from flowing blood in the human finger. Attenuation of signals from arterial blood was greatly reduced when blood flow was decreased with the application of a tourniquet. This result demonstrated the sensitivity of the technique to the rate of blood flow. RF gradient coils can be used to generate very high RF gradients with submicrosecond rise times and minimal eddy currents. Therefore, this method may prove useful for imaging very slow, nonuniform flow through capillary beds and in the extravascular space. .A Karczmar GS; Tavares NJ; Moseley ME. .I 125628 .U 89316300 .S Radiology 8910; 172(2):367-71 .M Adolescence; Adult; Child; Child, Preschool; Human; Infant; Infant, Newborn; Magnetic Resonance Imaging/*; Reference Values; Thymus Gland/*AH/PA; Thymus Hyperplasia/DI; Thymus Neoplasms/DI. .T Normal and abnormal thymus in childhood: MR imaging. .P JOURNAL ARTICLE. .W Magnetic resonance (MR) imaging studies of 47 children without thymic disease were compared with those of 14 children with proved thymic abnormalities (eg, lymphoma, leukemia, hyperplasia) to evaluate the spectrum of MR features of the normal and abnormal thymus and to determine the best indicators of thymic disease. In healthy children younger than 5 years of age, the thymus had a quadrilateral shape and biconvex lateral contours. Older children and adolescents had a triangular thymus with straight lateral margins. The thymus appeared homogeneous with a signal intensity slightly greater than that of muscle on T1-weighted images and close to that of fat on T2-weighted images. Qualitative evaluation of gross thymic morphology (size, shape, margins, and signal intensity) usually was sufficient for distinguishing between the normal and abnormal thymus. The abnormal thymus generally was enlarged, multilobular, or inhomogeneous because of the presence of cystic degeneration, hemorrhage, septations, fibrosis, or calcification on pathologic sections. In patients with lymphoma, the presence of associated lymphadenopathy also was helpful in distinguishing the normal from the abnormal thymus. .A Siegel MJ; Glazer HS; Wiener JI; Molina PL. .I 125629 .U 89316301 .S Radiology 8910; 172(2):373-5 .M Bone Marrow/*AH/GD; Child; Child, Preschool; Female; Human; Infant; Magnetic Resonance Imaging/*; Male; Retrospective Studies; Sphenoid Bone/AH; Sphenoid Sinus/*AH/GD. .T Marrow conversion before pneumatization of the sphenoid sinus: assessment with MR imaging. .P JOURNAL ARTICLE. .W To evaluate the bone marrow change before pneumatization of the sphenoid sinuses in childhood, the authors retrospectively reviewed short repetition time/echo time midsagittal magnetic resonance images in 56 patients younger than 6 years. The signal intensity of the presphenoid bone marrow (anteromedial part of the sphenoid bone) was as low as that of muscle (grade 1) and remained the same as that of the basisphenoid and basiocicput in all infants (n = 6) younger than 6 months. Between 7 months and 2 years, most patients (24 of 27) exhibited fatty conversion of bone marrow limited to the presphenoid (grade 2). After 3 years of age, most patients demonstrated pneumatization (six of 12 at 3-4 years, eight of 11 at 5-6 years) in addition to the grade 2 findings (grade 3). The presphenoid exhibits signal intensity characteristics of fatty marrow before it is invaginated by the developing sphenoid sinus. Fatty change before pneumatization is a normal developmental process and should not be misinterpreted as a pathologic condition. .A Aoki S; Dillon WP; Barkovich AJ; Norman D. .I 125630 .U 89316303 .S Radiology 8910; 172(2):381-5 .M Adolescence; Adult; Brain/*ME/PA; Child; Child, Preschool; Female; Human; Iron/*ME; Magnetic Resonance Imaging/*; Male; Reference Values. .T Normal deposition of brain iron in childhood and adolescence: MR imaging at 1.5 T. .P JOURNAL ARTICLE. .W Magnetic resonance (MR) images of the brain in 285 patients between the ages of 2 and 25 years were retrospectively studied to determine the appearance of brain iron accumulation. The globus pallidus, red nucleus, substantia nigra, and dentate nucleus were evaluated with long TR/TE (repetition time/echo time) spin-echo sequences and staged. All four regions in most patients were initially hyperintense compared with white matter (stage I) before becoming isointense (stage II) and subsequently hypointense (stage III). The globus pallidus was the first to reach stage III, the red nucleus and substantia nigra were next, and the dentate nucleus was last. In general, decreased signal intensity (stage III) was not seen in these regions in patients less than 10 years old; in most patients it was seen by age 25 years. The dentate nucleus decreased in signal intensity more slowly and inconsistently; only one-third of patients had reached stage III by age 25 years. The temporal sequence of normal iron deposition as detected with MR imaging is helpful not only in the diagnosis of known iron-deposition diseases but also in the detection of iron-related pathologic changes. .A Aoki S; Okada Y; Nishimura K; Barkovich AJ; Kjos BO; Brasch RC; Norman D. .I 125631 .U 89316306 .S Radiology 8910; 172(2):393-7 .M Animal; Ferric Compounds/*DU; Image Enhancement/*MT; Liver Neoplasms, Experimental/*DI/SC; Magnetic Resonance Imaging/*MT; Magnetics; Mammary Neoplasms, Experimental; Neoplasm Transplantation; Rats; Support, Non-U.S. Gov't. .T Superparamagnetic iron oxide-enhanced MR imaging: pulse sequence optimization for detection of liver cancer. .P JOURNAL ARTICLE. .W The effects of magnetic resonance (MR) pulse sequences and timing parameters on tumor-liver contrast were studied in an animal model of metastatic liver cancer. Six spin-echo (SE), three inversion-recovery (IR), and four gradient-echo (GRE) sequences were evaluated at 0.6 T before and after injection of super-paramagnetic iron oxide. GRE techniques, irrespective of echo time and flip angle, showed the greatest change in signal intensity (enhancement) of the liver after administration of iron oxide. Single-acquisition GRE sequences (16 seconds) matched the contrast-to-noise ratio (C/N) performance of the most effective 6.4-minute SE sequences. Multiexcitation GRE sequences showed tumor-liver C/Ns per unit time that were significantly (P less than .05) higher than those achieved with SE and IR sequences. GRE sequences, which recruit intravoxel dephasing as an additional source of transverse relaxation enhancement (T2*), show a higher C/N per unit time and in this respect seem superior to SE and IR sequences for MR imaging with superparamagnetic iron oxide. .A Fretz CJ; Elizondo G; Weissleder R; Hahn PF; Stark DD; Ferrucci JT Jr. .I 125632 .U 89316307 .S Radiology 8910; 172(2):399-401 .M Animal; Comparative Study; Dogs; In Vitro; Radiographic Image Enhancement/*; ROC Curve; Stomach Diseases/*RA; Stomach Neoplasms/RA; Stomach Ulcer/RA. .T Subtle gastric abnormalities in a canine model: detection with low-dose imaging with storage phosphors and its equivalence to conventional radiography. .P JOURNAL ARTICLE. .W The authors compared low-dose (32% of standard exposure) storage phosphor digital imaging (system resolution: 0.2-mm pixels, 10 bits) with isovoltage 75-kVp conventional radiography (standard exposure) in the detection of subtle simulated gastric abnormalities by using air contrast barium studies. Subtle simulated abnormalities (3-7-mm polyps, 4-15-mm ulcer craters, 4-11-mm-diameter edema, and 11-12-mm linear ulcers) were produced in resected canine stomachs. Receiver operating characteristic analysis of 1,800 observations by six readers indicated that the digital images with and without high-frequency edge enhancement were equivalent to conventional radiographs (mean receiver operating characteristic areas [+/- standard deviation]: 0.76 +/- 0.06, 0.78 +/- 0.04, and 0.77 +/- 0.04, respectively). The accuracy of the diagnosis was equivalent for all three modalities. The following mean accuracies of negative and positive responses, respectively, for unenhanced digital, edge-enhanced digital, and conventional images were determined: 0.71 +/- 0.05 and 0.41 +/- 0.07, 0.71 +/- 0.04 and 0.51 +/- 0.09, and 0.68 +/- 0.04 and 0.43 +/- 0.05. It was concluded that low-dose storage phosphor air-contrast barium studies were equivalent to conventional radiography in the detection of subtle gastric abnormalities. .A Shin JH; Oestmann J; Hall D; Cardenosa G; McCarthy KA; Mrose HE; Pile-Spellman E; Rubens JR; Greene RE. .I 125633 .U 89316310 .S Radiology 8910; 172(2):415-20 .M Adolescence; Adrenal Cortex Diseases/CO/*DI/RA; Adrenal Glands/PA/RA; Adult; Child; Child, Preschool; Comparative Study; Cushing's Syndrome/*ET; Female; Human; Magnetic Resonance Imaging/*; Male; Tomography, X-Ray Computed/*. .T Cushing syndrome due to primary pigmented nodular adrenocortical disease: findings at CT and MR imaging. .P JOURNAL ARTICLE. .W Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of Cushing syndrome in infants, children, and young adults. It is characterized by non-adrenocorticotropic hormone-dependent hypersecretion of cortisol by multiple, pigmented nodules of hyperplastic adrenocortical cells. With a single exception, adrenal glands have been described as normal with computed tomography (CT) in all previous series. Eight patients had Cushing syndrome due to surgically proved PPNAD. Four of the eight patients had stigmas of Carney complex (lentigines, calcified Sertoli cell tumors of the testes, and cardiac and soft-tissue myxomas). CT and/or magnetic resonance (MR) imaging demonstrated unilateral or bilateral nodularity in five of six patients examined. Macronodules (greater than 10 mm) were seen in the two oldest patients. As the clinical presentation of Cushing syndrome in this group of patients may be atypical (severe osteoporosis or short stature), the detection of multiple, small adrenocortical nodules with CT or MR imaging supports, or may even suggest, the diagnosis of PPNAD. .A Doppman JL; Travis WD; Nieman L; Miller DL; Chrousos GP; Gomez MT; Cutler GB Jr; Loriaux DL; Norton JA. .I 125634 .U 89316313 .S Radiology 8910; 172(2):431-6 .M Comparative Study; Human; Iodine Radioisotopes/DU; Iodohippuric Acid/DU; Kidney/*RI; Methods; Renal Circulation/*; Support, Non-U.S. Gov't. .T Two-compartment, two-sample technique for accurate estimation of effective renal plasma flow: theoretical development and comparison with other methods. .P JOURNAL ARTICLE. .W Discordance between effective renal plasma flow (ERPF) measurements from radionuclide techniques that use single versus multiple plasma samples was investigated. In particular, the authors determined whether effects of variations in distribution volume (Vd) of iodine-131 iodohippurate on measurement of ERPF could be ignored, an assumption implicit in the single-sample technique. The influence of Vd on ERPF was found to be significant, a factor indicating an important and previously unappreciated source of error in the single-sample technique. Therefore, a new two-compartment, two-plasma-sample technique was developed on the basis of the observations that while variations in Vd occur from patient to patient, the relationship between intravascular and extravascular components of Vd and the rate of iodohippurate exchange between the components are stable throughout a wide range of physiologic and pathologic conditions. The new technique was applied in a series of 30 studies in 19 patients. Results were compared with those achieved with the reference, single-sample, and slope-intercept techniques. The new two-compartment, two-sample technique yielded estimates of ERPF that more closely agreed with the reference multiple-sample method than either the single-sample or slope-intercept techniques. .A Lear JL; Feyerabend A; Gregory C. .I 125635 .U 89316314 .S Radiology 8910; 172(2):437-41 .M Adolescence; Adult; Aged; Aged, 80 and over; Balloon Dilatation/*/MT; Female; Human; Male; Middle Age; Postoperative Complications/TH; Ureteral Obstruction/ET/RA/*TH; Urography. .T Dilation of benign ureteral strictures. .P JOURNAL ARTICLE. .W Balloon dilation of benign ureteral strictures was performed in 33 patients in a percutaneous antegrade (25 patients) or retrograde (eight patients) fashion followed by placement of a 7-10-F stent for 4-8 weeks. Dilation was possible in all patients. During the follow-up period of 1-40 months the overall success rate was 76%. The success rate in primary strictures at the ureteropelvic junction was 86%. Among 10 patients with postsurgical (pyeloplasty, ureteroenterostomy, and ureteroneocystostomy) anastomotic strictures, dilation was successful in 50%. Of six patients with postoperative strictures after calculus removal by ureterolithotomy or pyelolithotomy, four (67%) had good results. All patients with iatrogenic postureteroscopic strictures (five patients) or accidental ureteral ligation (two patients) had a normal pyelogram at follow-up. The success rate in acute strictures of less than 3 months duration was 88%; in strictures of more than 3 months duration the success rate was 67%. Cause, length, and duration of stricture are the prime determinants of success. Early intervention with balloon dilation is suggested. .A Beckmann CF; Roth RA; Bihrle W 3d. .I 125636 .U 89316315 .S Radiology 8910; 172(2):443-4 .M Communication/*; Female; Human; Interprofessional Relations/*; Mammography/*; Prospective Studies; Radiology. .T Communication problems after mammographic screening [see comments] .P JOURNAL ARTICLE. .W The authors prospectively assessed the effectiveness of requests for immediate additional evaluation or biopsy made on the basis of the interpretation of abnormal findings on screening mammograms. In 1,125 screening mammograms obtained in asymptomatic women referred by physicians, the findings in 63 (6%) were interpreted as requiring additional imaging or biopsy. Written reports were sent, and in all cases the office of the referring physician was notified directly by phone. Physicians were periodically contacted if no follow-up had been performed to resolve the questioned abnormality. In the first 2.5 months, no action had been taken in 40 of 63 (63%) of the recommendations. After additional calls, this diminished to 10 of 63 (16%) at 3.5 months, but at 4.5 months four of 63 (6%) patients had not undergone the recommended additional studies. These results suggest the need for development of systems to ensure prompt action in patients with abnor