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10,001,700 | Chemical characterization of penta-, hexa-, hepta-, octa-, and nonaglycosylceramides of rat small intestine having a globoside-like terminus. | [
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10,001,701 | A novel series of glycosphingolipids has been isolated from the nonepithelial part of rat small intestine. A mixed fraction containing 3 major components corresponding to glycolipids with 5, 6, and 7 sugars and 2 minor components with 8 and 9 sugars was characterized. The structure of the major components was deduced by mass spectrometry and proton NMR spectroscopy of nondegraded permethylated and permethylated-reduced (LiAlH4) derivatives and gas-liquid chromatography of degradation products of native, permethylated, and permethylated-reduced glycolipids. The structures of the penta-, hexa-, and hepta-glycosylceramides were found to be GalNAcp beta 1 leads to (3Galp alpha 1 leads to)2-44Galp beta 1 leads to 4Glcp beta 1 leads to 1Cer. By analogy reasoning, supported by mass spectrometry, the octa- and nonaglycosylceramides were concluded to have 1 and 2 additional internal leads to 3Galp alpha 1 leads to 3 structures, respectively. A pentaglycosylceramide fraction from another rat strain was also isolated. The NMR spectra were in agreement with 2 isomeric structures of which 1 had the internal alpha 1 leads to 4 linkage replaced by an alpha 1 leads to 3 linkage. The fatty acids of all components were nonhydroxy 16:0 to 24:0 acids with the 18:0 homologue as dominating species. The major base was sphingosine and possibly monohydroxy 18:1 base in the larger glycolipids. This is a novel series of structures with a terminal saccharide identical with isoglobotetraoxylceramide (cytolipin R). The glycosyltransferase for the terminal GalNAc beta 1 leads to 3 of cytolipin R may possibly be identical with the enzyme adding the terminal sugar of this novel series. This is supported by the presence in the same tissue of probable precursor glycolipids with 4 to 8 hexoses. | [
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10,001,702 | The origin of the intermediates detected in the folding of swine pepsinogen. | [
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10,001,703 | Phosphorylation of dephospho-ATP citrate lyase by the catalytic subunit of cAMP-dependent protein kinase. | [
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10,001,704 | The native form of ATP citrate lyase (2 mol of phosphate/tetramer) and the dephospho-ATP citrate lyase (phosphate-free) purified to homogeneity from rat liver, are phosphorylated by ATP and by the catalytic subunit of cAMP-dependent protein kinase from rabbit muscle. A total of 2 mol of phosphate/tetramer were incorporated into native enzyme, while with the dephospho form, 4 mol of phosphate were incorporated. The phosphopeptides resulting from trypsin treatment which were isolated from phosphorylated forms of both native enzyme and the dephospho enzyme were similar. The ATP citrate lyase, phosphorylated to an extent of 4 mol of phosphate/tetramer, has the same Vmax as the native enzyme (2 mol of phosphate/tetramer). Native ATP citrate lyase, trypsin-treated to remove the phosphopeptide, could not be phosphorylated by the catalytic subunit of cAMP-dependent protein kinase from rabbit muscle, suggesting a common trypsin-sensitive specific phosphorylation site. The phosphorylation rate varied with pH in potassium phosphate, imidazole/HCl, and Tris/HCl buffers. Divalent cations were essential for the activity of the protein kinase. The apparent Km value for ATP was found to be 50 microM. | [
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10,001,705 | Isolation and characterization of mouse articular cartilage proteoglycans using preformed CsCl density gradients in the Beckman Airfuge. A rapid semi-micro procedure for proteoglycan isolation. | [
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10,001,706 | Substrate specificity and other properties of alpha-L-fucosidase from human serum. | [
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10,001,707 | The purification and characterization of an exo-beta (1 going to 3)-glucanohydrolase from sea urchin eggs. | [
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] |
10,001,708 | An exo-beta (1 going to 3)-glucanohydrolase (EC 3.2.1.6) of sea urchin eggs (Strongylocentrotus purpuratus) was purified to homogeneity by DEAE-cellulose chromatography followed by affinity chromatography on gluconolactone-Sepharose. The increase in specific activity is 800- to 1500-fold. The native enzyme exists in aggregated forms on nondenaturiung gels, with a subunit molecular weight on sodium dodecyl sulfate gels of 68,000. The enzyme is stabilized by polyethylene glycol and retains activity in 0.2% sodium dodecyl sulfate. With soluble laminarin as substrate (0.67 mg/ml), the temperature optimum is 60 degrees C (pH 6.0) and the pH optimum is 5.4 (40 degrees C). The egg glucanase does not exhibit Michaelis-Menten kinetics, exhibiting instead sigmoidal kinetics with a Hill coefficient of 1.6. The maximum velocity is 80 mumol of glucose released from soluble laminarin min-1 mg-1 protein. The half-maximum velocity (at pH 6.0, 40 degrees C) occurs at about 58 micrograms of laminarin ml-1. The glucanase is inhibited by D-1,5-gluconolactone, D-erythritol, and DL-threitol. This affinity method of glucanase purification may be important in the study of glucanases from other sources. | [
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10,001,709 | Regulation of elastin synthesis in developing sheep nuchal ligament by elastin mRNA levels. | [
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10,001,710 | Levels of elastin production in explant culture of fetal sheep nuchal ligament and corresponding levels of translatable elastin mRNA were determined in parallel studies during a period of rapid growth of the embryo. The identity of the explant culture and cell-free products was confirmed by peptide mapping, immunoprecipitation, and the characteristic lack of histidine and methionine. Elastin production was quantitated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and radioimmune precipitation. The translation products could be labeled with methionine only when NH2-terminally donated as f-Met-tRNAfMet. Explant cultures showed a large rise in elastin production from 70 days after conception to 150 days after conception. Cell-free translation of RNA demonstrated a parallel in elastin mRNA levels and in elastin mRNA per cell. It appears, therefore, that the marked emphasis the differentiating nuchal ligament places on elastin production is modulated, at least in part, by the quantities of available elastin mRNA. | [
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10,001,711 | Evidence that a Na+/Ca2+ antiport system regulates murine erythroleukemia cell differentiation. | [
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10,001,712 | The Na+ and Ca2+ transport properties of cultured murine erythroleukemia (MEL) cells have been investigated. We have previously shown that amiloride prevents dimethyl sulfoxide-induced MEL cell differentiation via inhibition of an essential Ca2+ influx (levenson, R., Housman, D., and Cantley, L. (1980) Proc. Natl. Acad. Sci. U. S. A. 77, 5948-5952). Here we show that external Na+ inhibits Ca2+ influx and stimulates Ca2+ efflux from uninduced MEL cells. Increasing the internal Na+ concentration by a brief incubation of cells with ouabain stimulates the rate of 45Ca2+ influx. Amiloride (40 microM) completely blocks the external Na+-stimulated 45Ca2+ efflux and external Na+-inhibitable 45Ca2+ influx. The same concentration of amiloride had no significant effect on net Na+ uptake. These results suggest that a significant fraction of Ca2+ flux across the MEL cell plasma membrane occurs via a Na+/Ca2+ antiport system and that amiloride prevents differentiation by blocking Ca2+ influx through this system. The importance of a Na+/Ca2+ antiport system for MEL cell differentiation is supported by the following observation: increasing the cellular Na+ level by a brief treatment with ouabain plus monensin accelerates MEL cell commitment as effectively as adding the Ca2+ ionophore A23187. We suggest that dimethyl sulfoxide induces MEL cell differentiation by inhibiting the Na+ pump and consequently allowing Ca2+ influx through the Na+/Ca2+ antiport. | [
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10,001,713 | Roles of Na+ and K+ in alpha-aminoisobutyric acid transport by the marine bacterium Vibrio alginolyticus. | [
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10,001,714 | Effects of monovalent cations on alpha-aminoisobutyric acid (AIB) transport were examined in the marine bacterium Vibrio alginolyticus. In K+-containing cells, AIB was actively accumulated only in the presence of Na+, and the addition of K+ had essentially no effect. On the other hand, K+-depleted and Na+-loaded cells required K+ as well as Na+ for the accumulation of AIB against its concentration gradient. The characterization of the roles of Na+ and K+ in AIB transport was performed by manipulation of intra- and extracellular cation compositions. K+ concentration gradient (K+in greater than K+out) was not essential for the Na+-dependent AIB uptake. Na+ extrusion against its concentration gradient in Na+-loaded cells occurred only in the presence of K+(Rb+). Half-maximal stimulations of the Na+ extrusion and AIB uptake by K+ were observed at K+ concentration near apparent Km for K+ transport. Finally, in the presence of the Na+ electrochemical gradient (toward the inside), K+ was not necessary for AIB uptake. From these results, it was concluded that the Na+-dependent AIB uptake is driven by the Na+ electrochemical gradient across the membrane and that K+ is required for AIB uptake only for the generation of the Na+ electrochemical gradient. | [
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10,001,715 | The free coenzyme A requirement of animal fatty acid synthetase. Participation in the continuous exchange of acetyl and malonyl moieties between coenzyme a thioester and enzyme. | [
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] |
10,001,716 | A hypothesis that the existence of common binding sites for acetyl and malonyl moieties on the animal fatty acid synthetase necessitates that free CoA be available continuously to facilitate unloading of inappropriately bound acetyl or malonyl moieties, allowing initial access of an acetyl moiety and subsequent access by malonyl moieties to the site of chain elongation, was formulated and tested. The unloading of acetyl or malonyl moieties from the enzyme was blocked by a CoA-scavenging system and the enzyme was unable to reload with the other substrate; the inhibition was relieved by the addition of CoA or pantetheine. The freely reversible nature of the loading/unloading reaction was established as follows. CoA or pantetheine, but not S-acetyl-N-acetylcysteamine, could act as donor or acceptor for acetyl moieties in the loading or unloading reactions; incubation of fatty acid synthetase, acetyl-CoA, and [G-3H]CoA resulted in the formation of acetyl-[G-3H]CoA in an amount consistent with the predicted equilibrium; and addition of a high concentration of CoA shifted the equilibrium toward unloading, leaving most of the substrate-binding sites vacant. These results support our hypothesis and provide a plausible explanation both for the requirement of free CoA by the fatty acid synthetase and for the observed inhibition of fatty acid synthesis by high concentrations of CoA. | [
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10,001,717 | On the chemistry and biochemistry of 3-mercaptopyruvic acid, the alpha-keto acid analog of cysteine. | [
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10,001,718 | 3-Mercaptopyruvate, generally believed to be formed by enzymatic transamination of L-cysteine and by the oxidative deamination of L-cysteine, has been found to exist in solution, in equilibrium with the cyclic dimer, 2,5-dihydroxy-1,4-dithiane-2,5-dicarboxylic acid; the equilibrium markedly favors the cyclic dimer in aqueous solution at pH 5-7. However, in neutral solutions, and especially in alkaline solution, 3-mercaptopyruvate undergoes very rapid and irreversible conversion to an acyclic aldol dimer. The rate of aldol dimerization is about 100 times greater than that of pyruvate dimerization under comparable conditions. Thus, 10 mM solutions of 3-mercaptopyruvate at pH 7.2 lose about 75% of their lactate dehydrogenase reactivity in 90 min at 25 degrees C. The present findings explain the previous observation that 3-mercaptopyruvate exhibits anomalous behavior in transamination with glutamine. Oxidative deamination of L-cysteine by L-amino acid oxidase yields the highly reactive imine, 2-imino-3-mercaptopropionic acid, which can be quantitatively trapped with semicarbazide. In the absence of semicarbazide, almost quantitative formation of ammonia from L-cysteine occurs with only a 10-20% yield of alpha-keto acid, none of which is 3-mercaptopyruvate; however, 3-mercaptopyruvate may be trapped as 3-mercaptolactate when the oxidase reaction is carried out in the presence of lactate dehydrogenase and NADH. One of the physiological functions of glutamine transaminase may be to convert 3-mercaptopyruvate to L-cysteine, thus preventing its loss through further transformations. In the course of this work it was found that hemithioketals (formed by reaction of cysteine with alpha-keto acids) are substrates of L-amino acid oxidase. Evidence for the cyclic dimer in the solid and vapor states of 3-mercaptopyruvate has been found through infrared and mass spectroscopic observations. | [
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10,001,719 | Phenylalanine hydroxylase. Correlation of the iron content with activity and the preparation and reconstitution of the apoenzyme. | [
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10,001,720 | Phenylalanine hydroxylase requires 1.0 mol of iron/Mr = 50,000 subunit for maximal activity. A direct correlation between iron content and specific activity has been demonstrated through a comparison of enzyme activity and iron bound per subunit for various enzyme preparations and a measurement of the remaining activity upon partial and total removal of the iron by chelation. Apoenzyme has been prepared that can be reactivated by addition of Fe(II) aerobically or of Fe(III) anaerobically. A comparison of the native and reconstituted phenylalanine hydroxylase shows the latter behaves identically upon affinity and Chelex column chromatography as well as precipitation with ammonium sulfate supporting its close similarity to the native enzyme. | [
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10,001,721 | Purification and characterization of S-acyl fatty acid synthase thioester hydrolase which modifies the product specificity of fatty acid synthase in the uropygial gland of mallard. | [
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10,001,722 | Bovine liver mitochondrial monoamine oxidase is not an iron-dependent enzyme. | [
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10,001,723 | It has been reported that rat liver monoamine oxidase is an iron-dependent enzyme. Calculations from reported data suggest that rat liver monoamine oxidase contains 2 g atoms of iron/mol of enzyme. However, our data over a 16-year period show that our purified bovine liver monoamine oxidase does not contain sufficient iron to justify being considered an iron protein. In order to ensure the correctness of the iron content, two microchemical analyses and atomic absorption spectroscopy were used to determine the iron content of wet ashed samples. The iron content was also determined during successive steps of enzyme purification and was found to decrease rather than increase. Monoamine oxidase, being a hydrophobic outer membrane enzyme, is very difficult to purify and detailed tests for homogeneity are necessary. Our preparations show a single band when examined by sodium dodecyl sulfate-polyacrylamide disc electrophoresis and behave as a pure protein by end group analysis. Thus, bovine liver monoamine oxidase is not an iron-dependent enzyme. | [
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10,001,724 | Altered proteoglycan synthesis by epiphyseal cartilages in culture at low SO4(2-) concentration. | [
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10,001,725 | Proteoglycan Type H formed by incubation of chick embryo epiphyseal cartilages with [14C]glucosamine altered its buoyant density as the concentration of SO4(2-) in medium was lowered from 300 to 0 microM. At the highest SO4(2-) concentration, the labeled product was essentially identical with unlabeled proteoglycan Type H (i.e. the molecules already preformed in ovo) with respect to the buoyant density and hyaluronic acid-binding activity. With decreasing the SO4(2-) concentration in medium, the products showed a gradual decrease in the buoyant density with no apparent change in the hyaluronic acid-binding activity. This change of buoyant density was directly related to a decrease in average sulfation degree of the chondroitin sulfate moiety, which in turn reflected an increase in the ratio of low sulfated chondroitin chains (Chn) to high sulfated chondroitin sulfate chains (CS) per proteoglycan molecule. At intermediate SO4(2-) concentrations, 50 and 100 microM, the labeled products were of hybrid type containing both Chn and CS chains. Treatment of such hybrids with trypsin yielded, in each case, a mixture of CS- and Chn-carrying peptide fragments with an average buoyant density slightly lower than that of the parent proteoglycan. In no case were these fragments separated into two discrete groups corresponding to Chn-rich peptides and CS-rich peptides, respectively, suggesting that the two types of polysaccharide chain are rather evenly distributed along the core protein. | [
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10,001,726 | Binding and endocytosis of cluster glycosides by rabbit hepatocytes. Evidence for a short-circuit pathway that does not lead to degradation. | [
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] |
10,001,727 | Synthetic cluster glycosides containing either one, two, or three galactosyl or lactosyl residues per ligand were used to test the effect of carbohydrate clustering on binding by the rabbit hepatic Gal/GalNAc-binding lectin using either isolated rabbit hepatocytes or the solubilized, affinity-purified lectin. The tris- and bis-glycosides were superior to the mono-glycosides for inhibition of 125I-asialoorosomucoid binding to rabbit hepatocytes at 0 degrees C. The concentrations of the tris-glycosides required for 50% inhibition of 125I-asialoorosomucoid binding (4-8 microM) to hepatocytes were 50-100 times lower than the concentrations of the corresponding mono-glycosides required for 50% inhibition (400-500 microM). The isolated lectin, however, did not effectively discriminate between the mono-, bis-, and tris-glycosides, possibly indicating an organizational difference between the lectin in the cell membrane and the isolated lectin. When the cluster glycosides were labeled with 125I-tyrosine, it was shown that the tris- and bis-galactosides were bound to the hepatocytes at 37 degrees C, and that binding was followed by a step that led to ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid resistance, probably internalization. The process could be specifically inhibited by the neoglycoprotein Gal44-AI-bovine serum albumin, or by IgG specific for the hepatic lectin, but not by preimmune IgG. Internalization of the cluster glycosides did not lead to accumulation of ligand inside the cell, nor to degradation. Instead, the ligands were quickly released from the cells. | [
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10,001,728 | Effects of 3-methylcholanthrene, beta-naphthoflavone, and phenobarbital on the 3-methylcholanthrene-inducible isozyme of cytochrome P-450 within centrilobular, midzonal, and periportal hepatocytes. | [
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10,001,729 | Total ankle arthroplasty. Clinical study of fifty cases. | [
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10,001,730 | A prosthesis for the ankle joint that I designed in 1973 was implanted in fifty patients who otherwise would have required fusion of the ankle to relieve severe pain. The design of the device allows about as much motion as in the normal ankle. During implantation of the prosthesis the dome of the talus is not resected and only one centimeter of the distal end of the tibia is removed. If the prosthetic replacement is unsuccessful, fusion of the ankle can more easily be achieved secondarily if it should become necessary. Review of the cases of these fifty patients showed that the best results were obtained in the patients with degenerative arthritis whose ankles were stable and not unduly deformed. A few patients with rheumatoid arthritis (four of ten) who were not on long-term steroid therapy also did well. Contraindications revealed by my experience include avascular necrosis of the talus, pseudarthrosis at the site of a previously attempted ankle fusion, and conditions causing talar tilt of 20 degrees or more. | [
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10,001,731 | Diaphyseal fractures of the humerus treated with a ready-made fracture brace. | [
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10,001,732 | Osteomyelitis of the symphysis pubis: a separate disease from osteitis pubis. Report of three cases and review of the literature. | [
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10,001,733 | We reviewed the case of three of our own patients who had osteomyelitis of the symphysis pubis, as well as those of twenty-five patients described in the literature. The early symptoms of osteomyelitis of the symphysis mimic those of osteitis pubis. Osteomyelitis almost invariably is preceded by urological or gynecological surgery (often when a technical complication has occurred), and does not respond to shortterm antibiotic treatment. Characteristic radiographic findings develop. Osteomyelitis of the symphysis pubis should be treated by debridement and curettage, together with long-term treatment with an appropriately high dose of antibiotics. | [
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10,001,734 | A comparative evaluation of tibial component designs of total knee prostheses. | [
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10,001,735 | Three-dimensional finite-element stress analyses were used to compare the fixation of tibial component configurations of surface-replacement-type total knee prostheses, bases on the stresses in the cancellous bone, in the polymethylmethacrylate, and at the bone cement-bone interface. The results indicate that, in general, metal components provide lower system stresses than polyethylene components, particularly in the methacrylate and the cancellous bone, and that one-piece designs give lower bone cement-bone interface stresses compared with those with separated condylar components. Of the designs considered, a single-post, metal-backed design provided the lowest system stresses over-all. | [
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10,001,736 | Pudendal-nerve neurapraxia as a result of traction on the fracture table. A report of four cases. | [
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10,001,737 | Multiple joint osteonecrosis following short-term steroid therapy. Case report. | [
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10,001,738 | The effect on supination-pronation of angular malalignment of fractures of both bones of the forearm. | [
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10,001,739 | Ten fresh human upper-extremity cadaver specimens were tested for the effect of residual angulation from simulated fractures of both bones of the forearm on the potential for range of rotation of the forearm and for limitations of pronation and supination specifically. Ten and 20-degree angulations for the radius and ulna, such as might be encountered in all reasonable clinical situations, were tested. Little significant loss of forearm rotation resulted from angulations of 10 degrees in any direction. With 20 degrees of angulation, there was statistically significant and functionally important loss of forearm rotation. | [
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10,001,740 | Brucella osteomyelitis of the distal part of the femur. A case report. | [
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10,001,741 | Pigmented villonodular synovitis of a lumbar vertebral facet joint. | [
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10,001,742 | Congenital absence of the thenar muscles. | [
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] |
10,001,743 | Inadequate reduction of congenital dislocation of the hip. | [
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10,001,744 | Computed tomography in congenital hip dislocation. The role of acetabular anteversion. | [
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10,001,745 | Computed tomography usually can provide accurate documentation of the adequacy of a reduction in congenital dislocation of the hip. It should supplement other radiographic examinations when the status of a reduction is in question because the patient is wearing a plaster cast. The computed tomography scan provides a clear image of the reduction in the transverse plane, so that anterior or posterior subluxation of the femoral head can be easily detected. In addition it allows direct measurement of acetabular anteversion which previously had not been possible with non-invasive studies in the living patient. Radiation exposure is less than that for conventional tomography. We used computed tomography in five patients with congenital dislocation of the hip and our study provided new evidence concerning the role of acetabular anteversion in this condition. Acetabular anteversion was increased on the dislocated side in each patient, and returned to normal as treatment progressed. | [
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10,001,747 | To determine whether proteoglycans or glycosaminoglycans from human achondroplastic cartilage are structurally abnormal, we isolated and characterized proteoglycans and glycosaminoglycans from fibular growth plates and from cartilage of the iliac crests of patients with achondroplasia. The glycosaminoglycans of both achondroplastic fibular growth plates and achondroplastic iliac-crest cartilage showed no differences from those isolated from normal tissues. Proteoglycans of achondroplastic iliac-crest cartilage were indistinguishable from those of controls. However, the proteoglycans of achondroplastic fibular growth plates showed higher proportions of proteoglycan aggregates, lower proportions of free proteoglycan monomers, higher intrinsic viscosities, and higher protein contents than those of age and sex-matched controls. The biochemical defect in achondroplasia does not involve an abnormality in the structure or formation of proteoglycan aggregates by proliferating chondrocytes, but appears to be related to abnormalities in chondrocyte proliferation and in the formation of a fully developed hypertrophic zone. | [
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10,001,748 | Scoliosis associated with limb-length inequality. | [
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10,001,749 | We reviewed the records and physical findings of twenty-three young adults who had had significant untreated limb-length inequality, present since childhood. The spine was studied radiographically and clinically before and after neutralization of the discrepancy of limb lengths with a lift. Movements of the spine also were measured. A significant asymmetry of lateral flexion of the spine remained in nearly all of the patients after neutralization of the discrepancy. The lumbar scoliosis associated with the limb-length inequality was compensatory and non-progressive, but abnormalities of the Cobb angle and of axial rotation remained in the young adults. No relationship was found between the underlying cause of the anisomelia or its duration and the severity of the spinal abnormality. The scoliosis was minor in patients with discrepancies of less than 2.2 centimeters. No patients complained of significant discomfort in the back, nor were degenerative radiographic changes evident there. | [
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] |
10,001,750 | High and low-dose aspirin prophylaxis against venous thromboembolic disease in total hip replacement. | [
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10,001,751 | Aspirin has been demonstrated to be an effective prophylactic agent against postoperative venous thromboembolic disease, but the optimum dosage is unknown. We compared the efficacy of daily doses of 3.6 grams of aspirin (high dose) with that of 1.2 grams (low dose) in 182 patients. All patients were more than forty years old and all underwent a total hip replacement. This randomized, prospective, double-blind study was done using only objective dta for diagnosis. Twenty-three (44 per cent) of fifty-two women who were treated with the low dose had thrombi, compared with eighteen (34 per cent) of fifty-three women who were given the high dose. Thrombi developed in thirteen (32 per cent) and in eighteen (49 per cent) of thirty-seven men who were given the high dose. There were no statistically significant differences among the four groups, nor was there a significant difference among the subgroups that were determined according to prior history of venous thromboembolic disease. Therefore, the higher dose of aspirin was neither more nor less effective than the lower dose. Our data continue to support the use of 1.2 grams in men. | [
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10,001,752 | Distal ulnar translocation in the treatment of giant-cell tumors of the distal end of the radius. | [
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10,001,753 | Two patients with a giant-cell tumor of the distal end of the radius were treated by en bloc resection of the distal part of the radius and by replacement of the resected segment with the translocated distal portion of the ipsilateral ulna. The blood supply to the ulna without detaching its soft-tissue attachments. The distal articular surface of the ulna was resected and the ulna was fused to the lunate and the scaphoid. The ulnar segment was internally fixed to the proximal segment of the radius and to the carpus with an intramedullary Steinmann pin. Both patients obtained a useful, pain-free extremity with more than 85 per cent of forearm rotation and 10 to 15 degrees of flexion-extension at the wrist. | [
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10,001,754 | Microvascular free bone transfer with revascularization of the medullary and periosteal circulation or the periosteal circulation alone. A comparative experimental study. | [
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10,001,755 | Two different types of vascularized rib grafts presently are used in clinical practice and as experimental models for investigations on free microvascular bone transfer: the posterior rib graft, including both medullary and periosteal blood supply to the bone; and the posterolateral segmental rib graft, supplied by periosteal vessels alone, Complete survival of bone after successful revascularization of the posterior type of graft is well established, but this graft has the disadvantage of a complicated dorsal dissection which has limited its clinical use. Instead, many microsurgeons have utilized the posterolateral rib segment, which is easy and safe to excise although its viability and adequate microcirculation have not yet been confirmed. In nine large dogs, we compared the viability and vascularity of bone after transfer of the two types of bone grafts by histological methods, fluorochrome bone-labeling, microangiography, and technetium scintigraphy. The grafts were transferred to the subcutaneous fat tissue in the groin, where blood supply was reconstituted by microvascular anastomoses to local donor vessels. The results suggest that a bone transplant with revascularization of periosteal only established a collateral circulation to medullary vessels, and that there is no difference in viability of the two kinds of grafts. | [
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10,001,756 | Variations in the intrinsic mechanical properties of human articular cartilage with age, degeneration, and water content. | [
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10,001,757 | In a series of 103 specimens from the lateral facet of the human patella, the intrinsic mechanical properties of articular cartilage were measured using a confined compression creep test. By considering the cartilage as a porous, permeable solid filed with fluid, this experimental procedure allowed the determination of the intrinsic equilibrium modulus of the cartilage matrix and its permeability to fluid flow. The intrinsic equilibrium modulus and the permeability both were highly correlated with the water content of the tissue; as water content increased, the matrix of the tissue became softer and more permeable. There was only a marginal decrease in the equilibrium modulus of the tissue with increasing age and surface degeneration. The permeability of the cartilage matrix was not significantly correlated with age or degeneration. | [
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] |
10,001,758 | Ollier's Disease. An assessment of angular deformity, shortening, and pathological fracture in twenty-one patients. | [
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10,001,759 | A retrospective review of twenty-one patients with Ollier's disease showed that the lesion involved the femur and tibia most frequently, and that those bones accounted for the large majority of clinical problems. Angular deformities were common; 80 per cent of the affected femora had clinically significant varus or valgus angulation in the distal part and 42 per cent of the affected tibiae had proximal or distal deformity. The apex of the angulation, when present, was metaphyseal, with the concavity on the side that was more extensively involved by the enchondromas. Osteotomies were done frequently to correct angulation; all healed well. Deformity in the distal part of the femur frequently required repeat osteotomy to achieve a straight bone at skeletal maturity, The extent of shortening, which always was present in the involved limb, closely paralleled the extent of involvement, The discrepancies in limb lengths prior to surgical treatment averaged 9.8 centimeters (range, 4.3 to 35.7 centimeters). Epiphyseal arrest, when appropriately timed, was effective in correcting or limiting the discrepancies, but partial (medial or lateral) epiphyseal arrest to correct angular deformity was ineffective. Diaphyseal lengthening was done on six occasions, once in the femur and five times in the tibia and fibula, with good results. Fourteen pathological fractures occurred in seven of the twenty-one patients, and all healed uneventfully with conservative treatment. | [
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10,001,760 | Decreased glucocorticoid receptor binding in adrenal insufficiency. | [
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10,001,761 | To examine the effect of glucocorticoid deficiency on the glucocorticoid receptor, we examine the binding of [3H] dexamethasone to lymphocytes in normal subjects and patients with adrenal insufficiency before and after glucocorticoid replacement therapy. Using a whole cell competitive binding assay, normal human lymphocytes had 5977 +/- 1487 (mean +/- SD) binding sites/cell and a dissociation constant of 10 +/- 2 nM. Lymphocytes from patients with untreated adrenal insufficiency had fewer binding sites (3364 +/-322) and a 2-fold increase in binding affinity (5.4 +/- 0.9 mM). The administration of conventional replacement doses of cortisone acetate for 6 months caused no change in receptor number, but was associated with a decrease in binding affinity toward normal. After long term glucocorticoid replacement therapy, binding parameters were similar to those in patients before treatment. The physiological implications of the decreased receptor number and increased binding affinity in adrenal insufficiency remain to be elucidated. | [
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10,001,762 | Radioimmunoassay and metabolism of the catechol estrogen 2-hydroxyestradiol. | [
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10,001,763 | Plasma levels of 2-hydroxyestradiol (2-OHE2) were measured using a new RIA procedure. Values were below the detection limit of the assay (less than 10 pg/ml), except in the third trimester of pregnancy, when they rose to approximately 15 pg/ml. The infusion of 130 microgram/h purified 2-OHE2 elevated its plasma concentration to 155 pg/ml, consistent with a plasma MCR (MCRp) of approximately 20,000 liters/day. The infusion of [3H] 2-OHE2 to equilibrium and chromatographic separation of the extracted plasma metabolites yielded an MCRp of about 13,000 liters/day; the major plasma metabolite comigrated with 2-methoxyestradiol, and [3H] xi-methoxyestrone was also formed. The MCRp, of 2-OHE2 is approximately half that of 2-hydroxyestrone (2-OHE1), but much higher than those of other steroids. As is true for 2-OHE1, the clearance of 2-OHE2 must occur primarily in the blood compartment. Together, the measured MCRp values and estrogen receptor affinities of 2-OHE2 and 2-OHE1 predict a relative potency for effects upon gonadotropin secretion which is close to that observed in vivo. | [
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10,001,764 | Bioassayable luteinizing hormone during childhood and adolescence and in patients with delayed pubertal development. | [
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10,001,765 | Evolution of thyroid 127I stores measured by X-ray fluorescence in subacute thyroiditis. | [
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] |
10,001,766 | Evaluation of the thyroid iodine content by x-ray fluorescence was performed in 13 patients throughout the course of subacute thyroiditis. In the initial hyperthyroid phase of the disease, the iodine stores of the thyroid were not completely depleted. The iodine content (6.5 +/- 3 mg) was about 2.5 times lower than normal values when thyroiditis had developed in a normal thyroid (10 patients); in 3 patients with goiter, it was elevated (29.6 +/- 6.7 mg) but was still within the normal range of euthyroid goitrous patients. After clinical remission, the iodine content of the gland increased only in two patients (+105% and +43% over the initial value, respectively). For the other patients, the iodine content decreased (from -5% to -100% of the initial value). Restoration of iodine stores occurred subsequently and appeared to be a slow and progressive phenomenon; in six patient, the iodine content was still below normal values 12 months after clinical remission (6.6 +/- 1.6 mg). These data suggest that the course of subacute thyroiditis might be longer than would appear from the clinical data, the hormonal assays, or the radioactive thyroid uptake data. | [
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10,001,767 | Abnormal regulation of parathyroid hormone release by calcium in secondary hyperparathyroidism due to chronic renal failure. | [
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10,001,768 | Dispersed parathyroid cells were employed to study calcium-regulated parathyroid hormone (PTH) release in severe secondary hyperparathyroidism due to chronic renal insufficiency. Cell preparations were obtained from 16 parathyroid glands of 6 patients undergoing subtotal parathyroidectomy for parathyroid bone disease and/or hypercalcemia. The effects of increasing ambient calcium concentration on immunoreactive PTH release in vitro were assessed and compared with results observed in cells prepared from 7 adenomas and 6 normal parathyroid glands. There was no difference in maximal PTH release for the 3 types of tissue (mean +/- SEM, 8.48 +/- 1.9 , 8.1 +/- 3, and 10.1 +/- 0.78 ng/10(5) cells. h respectively). In 14 of 16 hyperplastic glands, 6 of 7 adenomas, and all of the normal glands, PTH release was inhibited more than 50% by 2-3 mM calcium (suppressible glands). Of the normal glands, half of the maximal inhibition of PTH release (the set-point) occurred at less than 1.03 mM calcium in 5 of 6 cases. In 12 of 14 suppressible hyperplastic glands and all of the 6 suppressible adenomas, on the other hand, the set-point was 1.03 mM or higher (p less than 0.01 and P less than 0.002, respectively). Thus, in severe secondary parathyroid hyperplasia due to chronic renal insufficiency, there is frequently an increase in the set-point for calcium without a change in the maximal secretory rate per cell. Abnormal calcium-regulated PTH release at the cellular level, therefore, is not limited to parathyroid neoplasia (i.e. adenoma or primary hyperplasia), but may occur in secondary hyperplasia as well. | [
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10,001,769 | Methimazole: an alternative route of administration. | [
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10,001,770 | Methimazole was administered orally and rectally in a single dose of 60 mg to six euthyroid volunteers (three females and three males). Blood levels of methimazole were the same whether administered by the oral or rectal route, with peak levels of 1184 +/- 118 and 1163 +/- 150 (+/-SEM) ng/ml respectively. This study provides evidence that the rectal administration of methimazole may be an alternative to treating hyperthyroid patients who are unable to take this drug by mouth. | [
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10,001,771 | The effect of corticosteroid-binding globulin on the in vitro incorporation of thymidine into human lymphocytes. | [
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10,001,772 | The purpose of these studies was to examine the inhibitory effect of human corticosteroid-binding globulin (CBG) on the mitogenic effect of phytohemagglutinin on cultured human lymphocytes. We found that CBG could inhibit the incorporation of [14C] thymidine into lymphocytes, but the observed inhibition could be accounted for by the cortisol which was bound to the purified CBG, CBG stripped of cortisol or bound to 11-deoxycortisol was inactive in this assay. | [
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10,001,773 | Production of a highly specific monoclonal antibody progesterone. | [
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10,001,774 | A progesterone monoclonal antibody which may be used in the development of a sensitive and specific immunoassay is described. The preparation involved isolation of spleen cells from Balb/c mice immunized with progesterone 11 alpha-hemisuccinate-bovine serum albumin conjugate, which were then fused with two different mouse myeloma cell lines. Hybridomas secreting antibody to progesterone were detected by immunoassay and cloned in soft agar. Five percent of the resulting clones secreted antibody; these clones originated from cultures producing very little antibody, and so might easily have been discarded. THe monoclonal antibody obtained is highly specific and has a binding affinity of approximately 1.7 X 10(9) M-1, so it may be advantageously used in the detection of progesterone in body fluids. | [
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10,001,776 | Corticosteroid synthesis in the human adrenal cortex requires a supply of cholesterol which can be derived from both local synthesis and the uptake of plasma lipoproteins. Studies with cultured adrenal cells have shown that such uptake is mediated through the interaction of plasma low density lipoproteins (LDL) and a specific cellular receptor (the LDL receptor). In the present study we have examined parameters of adrenal corticosteroid production in a patient with phenotypic abetalipoproteinemia (on the basis of homozygous hypobetalipoproteinemia) and in three of her relatives with inherently low levels of LDL (heterozygous hypobetalipoproteinemia). These studies sought to determine whether the absence of LDL or an inherent reduction in their plasma concentration results in alterations in corticosteroid production both under basal conditions and in response to prolonged stimulation with iv ACTH. Our results document normal parameters of corticosteroid production under basal conditions in both heterozygous and homozygous hypobetalipoproteinemia, but an impaired response to ACTH in the latter. This was manifested by significantly lower serum concentrations of cortisol as well as by reduced rates of excretion of 17OHCS, 17-ketosteroids, and urinary free cortisol during ACTH infusion. By inference, our results provide in vivo support for the view that plasma LDL serve as an important source of cholesterol for adrenal corticosteroid synthesis under conditions of sustained stimulation with ACTH. | [
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10,001,777 | The effects of age on the plasma catecholamine response to mental stress in man. | [
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10,001,778 | To determine if sympathetic nervous system activity is heightened during psychological stress in older adults, plasma norepinephrine (NE), epinephrine (EPI), heart rate, and blood pressure were measured in 10 healthy old (mean age, 68.5 yr) men and 10 healthy young (mean age, 26.6 yr) men during a 12-min mental stress test. Basal NE was higher in old than in young men (400 +/- 33 vs. 286 +/- 32 pg/ml: p less than 0.01). Consistent significant increases in plasma NE occurred only in the elderly and mean increases (delta) in NE during testing were significantly greater (P less than 0.01) in the old than in the young men. Compared to basal levels, plasma EPI increased by 2 min in both young (delta EPI, 50 +/- 20 pg/ml; P less than 0.02) and old subjects (delta EPI, 41 +/- 11; P less than 0.01) and remained significantly increased throughout the test. There was no difference in either basal or delta EPI between young and old men. Heart rate and blood pressure were significantly increased throughout testing for both age groups. Although the delta blood pressure during testing tended to be greater in the old men, this difference was not statistically significant. Conversely, the delta heart rate was greater in the young subjects (P less than 0.005). Since EPI increases were similar in old and young men, mental stress-related adrenomedullary activation does not appear to change with age. However, the increased plasma NE response in the elderly suggests that they have heightened activity of postganglionic sympathetic neurons during psychological stress. | [
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10,001,779 | The relationship between episodic variations of plasma prolactin and REM-non-REM cyclicity is an artifact. | [
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10,001,780 | The concept of concomitance between nadirs and peaks of plasma levels of PRL and, respectively, rapid eye movement (REM) and non-REM stages in sleep was reevaluated using 24 nighttime profiles of plasma PRL collected at 15-min intervals and the corresponding polygraphic recordings of sleep. The subjects were 5 healthy young male adults. Data were examined using the methodology described in the original report, consisting of averaging across individual nights PRL levels during REM and non-REM sleep stages as well as using a detailed spike by spike analysis of each individual pair of hormonal and sleep profiles. We showed that in our subjects, there was no relation, other than a purely random one, between episodic PRL fluctuations in plasma and REM-non-REM cycles. | [
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10,001,781 | Calcium phosphate metabolism and bone disease in patients with homozygous thalassemia. | [
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] |
10,001,782 | Calcium and phosphate metabolism were studied in 22 patients with homozygous thalassemia. The overall results showed no significant difference for serum calcium, phosphorus, alkaline phosphatase, immunoreactive parathyroid hormone, or 25-hydroxyvitamin D between thalassemic and control children. However, during the winter, serum 25-hydroxycholecalciferol levels were very significantly decreased in thalassemic children. A study of the hands showed thin metacarpal cortices related to increased resorption. Histomorphometric study of four iliac bone biopsies showed normal osteoclastic resorption and decreased bone formation. Prussian blue staining and x-ray electron microprobe analysis showed iron deposits inside the bone. Whether this finding is critical in the pathogenesis of the bone disease in unknown. | [
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10,001,783 | Dexamethasone-induced change in the sphingomyelin content of human polymorphonuclear leukocytes in vitro. | [
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10,001,784 | Human polymorphonuclear leukocytes were incubated with 8 x 10(-9) M dexamethasone for 2 h. A significant increase in the sphingomyelin content of the cells was found when 8 x 10(-8) M dexamethasone was used, with lesser changes being noted when the concentration was increased or decreased from this level. The increase in the phospholipid was blocked by the addition of cycloheximide to the incubation. Concurrent with the increase in sphingomyelin, an increase in sphingomyelinase was demonstrated. This increased enzymatic activity may have occurred secondary to the increase in substrate or may be involved in the reverse reaction, whereby phosphorylcholine and ceramide combine to form sphingomyelin. Other studies have demonstrated an effect of corticosteroids to suppress the production of superoxide anion and the importance of a membrane oxidase in the production of the anion. An action of dexamethasone to both suppress superoxide anion production and increase sphingomyelin content suggests a possible effect of the lipid changes upon the oxidase responsible for the production of the anion. | [
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10,001,785 | Metabolism of cortoic acids in man. | [
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10,001,786 | Administrated radioactive tracers of beta-cortolic or beta-cortolonic acids are excreted mostly unchanged, without significant alteration of the molecule at C-11 or C-20; a minor amount of cleavage to C-20 etianic acids occurs. Evidence was obtained for possible noncovalent complexing of the steroid acids to macromolecular components present in the enzyme preparation for hydrolysis of the urinary glucuronides; this complex can be dissociated by acidification to pH 2, and the acidic metabolites can then be readily extracted. The findings suggest that beta-cortoic acids are essentially terminal metabolites in man. | [
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10,001,787 | Progesterone synthesis by luteinized human granulosa cells in culture: the role of de novo sterol synthesis and lipoprotein-carried sterol. | [
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10,001,788 | Human granulosa cells cultured in the presence of estradiol, FSH, and LH secreted relatively little progesterone during the first 3-5 days of culture. The cells then underwent a morphological transformation associated with a 10-fold or more increase in progestin production. Cells not cultured with the tropic hormones usually produced progestin at a lower rate. Serum was required for the expression of maximal steroidogenic activity. Inhibitors of de novo sterol synthesis, ML-236B and 5-cholesten-3 beta,25-diol, did not affect progestin secretion by luteinized cells cultured in 20% serum, but these inhibitors did reduce [14C]acetate incorporation into sterols by 90%. ML-236B also did not affect hCG-stimulated progesterone secretion by the cells. However, when the cells were changed into lipoprotein-deficient medium, progestin production was markedly reduced within 24 h. The addition of low density lipoproteins (LDL) to the culture fluid restored progestin production, whereas high density lipoproteins tended to further inhibit steroid secretion. The effects of LDL on steroidogenesis were dose dependent and saturable. We conclude that luteinized human granulosa cells use LDL-carried sterol as the primary substrate for steroidogenesis. | [
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10,001,789 | Metabolic clearance rate and conversion ratios of [3H]2-hydroxyestrone in normal men. | [
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10,001,790 | Plasma 5 alpha-androstane-3 alpha,17 beta-diol and urinary 5 alpha-androstane-3 alpha,17 beta-diol glucuronide, parameters of peripheral androgen action: a comparative study. | [
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10,001,791 | Dynamic tests of prolactin secretion in hyperprolactinemic states: carbidopa-L-dopa and indirectly acting dopamine agonists. | [
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10,001,792 | Stimulatory effects of tolbutamide infusion on plasma glucagon in insulin-dependent diabetic subjects. | [
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10,001,793 | The effect of iv tolbutamide on endogenous glucagon levels was measured in nine insulin-dependent diabetic patients chosen because they evidenced no C-peptide response to beta-cell secretagogues. Basal glucagon levels were not suppressed by a sustained tolbutamide infusion; in fact, a slight stimulatory effect was observed at 5, 10, 30, and 45 min. In the absence of detectable insulin secretory capacity and suboptimal insulin replacement, tolbutamide appears to be a stimulus, not a suppressant, of glucagon secretion. | [
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10,001,794 | Normal cortical bone mass in patients after long term coumadin therapy. | [
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10,001,795 | Clinical delineation of the warfarin embryopathy and the recent discovery of osteocalcin (a vitamin K-dependent bone protein) suggest that coumadin therapy could adversely affect the skeleton. Using bone densitometry and metacarpal cortical width measurement, we found normal cortical bone mass in 17 adults receiving long term coumadin therapy. | [
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10,001,796 | The binding of human immunoglobulin G1 monomer and small, covalently cross-linked polymers of immunoglobulin G1 to human peripheral blood monocytes and polymorphonuclear leukocytes. | [
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10,001,797 | Covalently cross-linked dimers and oligomers composed of 2-4 subunits of monoclonal human IgG1 were prepared by incubation of purified monomeric IgG1 with glutaraldehyde followed by gelfiltration chromatography. Monomers, dimers, and oligomers then were labeled with (125)I and used to compare the binding properties of IgG Fc receptors on human peripheral blood monocytes and polymorphonuclear leukocytes (PMN). Binding of IgG1 to monocytes at 37 degrees C and of IgG1 polymers to PMN at 4 degrees C could be readily measured and were found to be reversible and saturable. Scatchard plots of binding were linear in each instance. Monocytes bound a mean of 20,200+/-6,800 molecules/cell of IgG1 monomer at saturation and comparable amounts of dimer or oligomer. The mean association constant (Ka) for binding of IgG1 monomer to monocytes was 8.6 x 10(8)M(-1) and the Ka for binding of dimer and oligomer were three-to fivefold greater.In contrast, PMN bound a mean of 460,000+/-130,000 molecules of IgG1 dimer at saturation and comparable amounts of oligomer. The Ka of binding in both cases was 100-1,000-fold lower than the Ka for binding of the same preparations to monocytes. Binding of labeled IgG1 to both cell types was more potently inhibited by unlabeled IgG1 and IgG3 than by IgG4 or IgG2. Binding of labeled polymers of IgG1 to monocytes was 10-100-fold more easily inhibited by monomeric IgG1 than was binding to PMN. Thus, there are significant quantitative and qualitative differences between the binding properties of Fc receptors present on monocytes and PMN. | [
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10,001,798 | Regulation of episodic growth hormone secretion by the central epinephrine system. Studies in the chronically cannulated rat. | [
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10,001,799 | Catecholamines are postulated to regulate growth hormone (GH) secretion by their influence on the release of two hypothalamic substances, somatostatin, which inhibits GH release, and GH-releasing factor, as yet unidentified. Extensive pharmacologic studies in man and animals indicate a stimulatory effect of central norepinephrine and dopamine on GH, but the function of epiphephrine (EPI) is uncertain. Furthermore, many of the agents used to study the role of catecholamines in GH regulation are not selective in that they affect adrenergic as well as nor-adrenergic and/or dopaminergic neurotransmission. In the present investigation, central nervous system (CNS) EPI biosynthesis was selectively interrupted with the specific norepinephrine N-methyltransferase inhibitors, SK & F 64139 (Smith, Kline & French Laboratories) and LY 78335, (Eli Lilly & Co. Research Laboratories) and the effects of central EPI depletion on episodic GH secretion in the chronically cannulated rat model were determined. Inhibition of CNS EPI synthesis with SK & F 64139 caused complete suppression of episodic GH secretion and concomitantly reduced the EPI level in the hypothalamus without affecting dopamine or norepinephrine. Administration of LY 78335 produced similar effects on pulsatile GH. Morphine-induced, but not clonidine-induced, GH release also was blocked by SK & F 64139. These results indicate that (a) the central EPI system has a major stimulatory function in episodic GH release, (b) morphine-induced GH release is mediated by the central EPI system, and (c) clonidine stimulates GH release by activation of postsynaptic alpha-adrenergic receptors. Drugs that affect CNS adrenergic systems have a potential role in the diagnosis and treatment of disorders of GH secretion. | [
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-0.04555637389421463
] |
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