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Biomedical subjects

S Baur

Publications and source records attributed to S Baur.

At least 55 records · Page 3Linked to original sources

Expression of the fragile site Xq27 in fibroblasts. II. Evidence for negative and positive clones from heterozygous females and possible relationship between frequency and phenotype.

An investigation of fibroblast clones from two females heterozygous for the Martin-Bell syndrome showed that the fibroblasts of these individuals consist of two sub-populations, one with cells expressing the fra(X)(q27) and another with cells in which this fragile site cannot be induced. This is to be expected and is in contrast to the fibroblast clones of hemizygous patients investigated earlier. The expression of fra(X)(q27) in females evidently depends on the presence of an X-linked defect with the normal allele inactivated on the other X chromosome. There may be a relationship between the mental status and the ratio of somatic cells with this defect on the active X and those cells with this defect on the inactive X chromosome in the heterozygotes. The divergence between the inactivation of the defective gene and expression of fra(X)(q27) on the late replicating X chromosome is discussed.

Adult↗

Cyclic nucleotides of canine antral smooth muscle. Effects of acetylcholine, catecholamines and gastrin.

1. The effects of acetylcholine, catecholamines and gastrin on the intracellular content of cyclic AMP and cyclic GMP in antral circular muscle have been determined. 2. Acetylcholine results in a significant but transient increase in intracellular cyclic GMP. 3. Isoproterenol and norepinephrine increase intracellular cyclic AMP. Based on half-maximal effective doses, isoproterenol is 2.7-times more effective than norepinephrine. The increase in intracellular cyclic AMP by both agents is inhibited by propranolol but not phentolamine, indicating that both agents act on the muscle cell by a beta-receptor-coupled mechanism. 4. Gastrin has no demonstrable effect on either cyclic AMP or cyclic GMP. This suggests that while gastrin and acetylcholine can produce a like myoelectric response in the muscle cell, the action of gastrin is mediated by a separate receptor, presumably on the muscle cell, and not by a release of acetylcholine.

Acetylcholine↗

Effect of hormonal and neuronal agents on adenylate cyclase from smooth muscle of the gastric antrum.

Smooth muscle adenylate cyclase of a membrane preparation of canine gastric antrum has been characterized, and the effect of hormonal and neuronal agents examined. The enzyme is active in the presence of Mg2+ or Mn2+, but is inhibited by Ca2+. The Km is 0.5 mM ATP, similar to the Km of skeletal muscle adenylate cyclase. The enzyme is activated by isoproterenol but not norepinephrine, consistent with a beta 2-catecholamine receptor-adenylate cyclase interaction. Secretin activates the enzyme in concentrations as low as 1 . 10(-11) M, while glucagon was effective only at 1 . 10(-6) M. Prostaglandin E1 and E2 have a biphasic effect with activation of adenylate cyclase at 1 . 10(-5) M and a small but significant inhibition of enzyme activity at 1 . 10(-11) M.

Adenylyl Cyclases↗

A specific gastrin receptor on plasma membranes of antral smooth muscle.

Plasma membranes with a 17 fold enrichment in 5'-nucleotidase over homogenate were prepared from antral smooth muscle. A specific gastrin receptor on the plasma membranes has been demonstrated. By Scatchard analysis receptor has a Kaff of 2x10(9)M(-1) and a binding capacity of 5x10(-14) moles/mg of membrane protein.

Animals↗

Insulin receptors of skeletal muscle: specific insulin binding sites and demonstration of decreased numbers of sites in obese rats.

A membrane preparation was obtained from rat striated muscle. The preparation used has been shown to contain plasma membranes by electron microscopy as well as by enrichment in specific activity of both a plasma membrane enzyme "marker" (5'-nucleotidase) and cell surface 125I-incorporated radioactivity. The characteristics of 125I-insulin binding to this striated muscle preparation were studied, and it was found that 125I-insulin readily and specifically binds to this membrane preparation. The binding reaction was time, pH, and temperature dependent with optimal steady-state binding conditions occurring at 20 degrees C and at pH 7.6. Under these conditions (20 degrees C, pH 7.6) skeletal muscle plasma membranes displayed little ability to degrade insulin. Binding of 125I-insulin was readily inhibited at physiologic concentrations of unlabeled insulin and the specificity of this receptor for insulin was demonstrated by finding that high concentrations of glucagon, b-LH, b-FSH, p-PRL, hCG, TSH, and HGH were without effect on 125I-insulin binding and that insulin analogues inhibited binding in proportion to their biologic activity. When membranes from older, fatter rats were compared to membranes from younger, lean animals, 5'-nucleotidase specific activity and insulin degrading activity were found to be comparable. On the other hand, insulin binding to membrane receptors was decreased 30%-40% in the older, fatter animals. Thus, these studies indicate that (1) specific insulin receptors exist in skeletal muscle plasma membranes, and (2) membranes from older, fatter rats have fewer receptors than those from younger, lean animals.

Age Factors↗

Duodenal immunoglobulin deficiency in graft versus host disease (GVHD) mice.

The small intestine is a well documented target organ in mouse and human GVHD, and diarrhea is a prominent part of the clinical GVHD syndrome. Although a plethora of systemic immune deficits has been documented in GVHD, the integrity of the small intestinal immune system has not been investigated. A correlation has not been demonstrated between systemic immune dysfuction and the incidence of lymphomas in mouse GVHD survivors. If gastrointestinal immune deficiency exists in mouse GVHD, its possible relationship to GVHD lymphomas, frequently abdominal. should be investigated. GVHD was produced in newborn BLA (C57 BL/Ka females x BALB-C males) mice house in a specific pathogen-free environment by the i.p. inoculation of 10(7) male BALB-C spleen cells. Control mice received syngeneic spleen cells. Twenty GVHD and 16 control mice were sacrificed at 3 weeks and specimens of duodenum were removed for routine histologic and immunofluorescent examination. All but one GVHD mouse (95%) had virtually absent duodenal IgA and IgM. Duodenal cellular fluorescence was demonstrated in all controls. A significant duodenal immunoglobulin deficit has been demonstrated in 3-week-old GVHD mice. The relationship of this finding to GVHD diarrhea, wasting, and neoplasia remains to be determined.

Animals↗

Comparison of 125-I-insulin binding and degradation to isolated rat hepatocytes and liver membranes.

UNLABELLED: We have compared the ability of rat liver plasma membranes and isolated hepatocytes to bind and degrade insulin. Isolated cells were prepared in two different ways: by mechanical separation of cells and by collagenase digestion of extracellular matric. In all studies the binding and degradative characteristics of both types of hepatocyte preparations were identical. Furthermore, with one exception, the binding characteristics of membranes and cells were also quite similar. The only exception concerned the amount of insulin bound by hepatocytes as compared to liver membranes. Thus, at concentrations of cells (1.2 times 10(6) cells per milliliter) and membranes (150 mug. protein per milliliter) that gave equal binding at insulin concentrations less than 100 ng./ml., the amount of insulin specifically bound at insulin concentrations greater than 100 ng./ml. was greater with use of hepatocytes. Additional studies indicated that, in contrast to membranes, at the higher insulin concentration only 75 per cent of the previously bound insulin could be recovered from hepatocytes. Thus, a nondissociable component exists; which probably represents intracellular radioactivity and appears to account for the higher specific insulin binding by cells at higher insulin concentrations. When insulin degradation was studied at the above hepatocyte and plasma membrane concentrations, cells degraded 30 per cent more insulin than did membranes. Kinetic analysis of these data revealed that the Km for insulin degradation (5 times 10(-7) M at 37 degrees) was the same for both systems wereas the Vmax was greater with use of hepatocytes. IN CONCLUSION: (1) Preparation of hepatocytes by collagenase digestion does not appear to alter insulin binding or degradation; (2) studies of liver membranes and isolated hepatocytes obtained from normal rats should yield similar information about insulin-receptor interaction as long as insulin concentrations less than 100 ng./ml. are used; (3) at very high insulin concentrations, some of the radioactivity appears to enter the cells; (4) the kinetics of insulin degradation by hepatocytes and liver membranes are similar; and (5) insulin degradation appears to be primarily a membrane phenomenon.

Animals↗

Cell surface immunoglobulin. 3. Isolation and characterization of immunoglobulin from nonsecretory human lymphoid cells.

Cells from an established line of Burkitt lymphoma (Daudi) were enzymatically radioiodinated, and labeled Ig from the cell surface was isolated and studied. Subcellular fractionation of labeled cells confirmed that intracellular proteins from the cytoplasm are not iodinated by this method. Radioactive Ig was identified as monomeric (8S) IgM, and an average of 10(5) Ig molecules was found per cell. Ig molecules could be released from the plasma membrane by detergent lysis under nonreducing conditions indicating that attachment of Ig to the plasma membrane occurs via noncovalent interactions. The ratio of micro/L radioactivity in surface Ig was the same as that of total cellular Ig radioiodinated in solution suggesting that a large portion of the Fc fragment is not buried within the membrane. In contrast to the results obtained with cell surface Ig, most intracellular Ig was found as "free" micro- and L chains regardless of whether lysates were labeled with (125)I or cells were labeled with leucine-(3)H. The results indicate that only a small percentage of the total Ig of Daudi cells is associated with the cell surface and suggest that covalent assembly of Ig occurs at or near the time that the molecule becomes part of the plasma membrane. Similarities between cell surface Ig on normal splenic lymphocytes and Daudi cells suggest that the latter is a neoplasm of bone marrow-derived lymphocytes.

Acrylamides↗

Cell surface immunoglobulin. II. Isolation and characterization of immunoglobulin from mouse splenic lymphocytes.

The proteins on surfaces of living splenic lymphocytes from normal BALB/c mice were iodinated enzymatically. Such cells were fractionated into two sub-populations: one composed almost exclusively of small lymphocytes and the other mainly of large lymphocytes and plasma cells. Specific immunoprecipitation of radiolabeled surface Ig obtained from lysates of these cell populations indicated that approximately 2-3% of the acid-precipitable radioactivity from the cell surface is Ig. Moreover, 95% of the H chain radioactivity from the Ig of the small lymphocyte fraction and 90% from the large lymphocyte-plasma cell fraction was characterized as micro by precipitation with anti-micro sera as well as by molecular weight determination on polyacrylamide gels in sodium dodecyl sulfate. The Ig was recovered from the cell surface in the form of an IgM monomer. Control experiments suggested that the monomer did not result from depolymerization of 19S IgM by the methods used to radiolabel and isolate the molecule. (3)H-tyrosine labeling of IgM produced by meyloma cells and radio-iodination of IgM in solution gave the same ratios of microL radioactivity as radiolabeling of IgM on cells, indicating that the tyrosine residues of L and micro-chains of cell surface IgM are available to the lactoperoxidase during the iodination. This is consistent with the hypothesis that cell surface IgM is entirely on the outside of the plasma membrane presumably attached to it by its Fc fragment. These results, together with previous reports by others, suggest that IgM, in its monomeric form, is the main antigen-specific receptor on lymphocytes of normal mice.

Animals↗

Natural family planning with and without barrier method use in the fertile phase: efficacy in relation to sexual behavior: a German prospective long-term study.

A large prospective long-term study with users of natural family planning (NFP) methods has been conducted to analyze the relation between unintended pregnancy rates and sexual behavior with special reference to barrier method use in the fertile phase. Seven hundred and fifty eight NFP beginners, 19-45 years of age, 14870 cycles, 28 unintended pregnancies were studied. Of the couples, 54.2% use NFP only or predominantly and 45.9% use mixed methods (additional barrier method use in the fertile phase in 55.7% of the cycles). The overall pregnancy rate after 12 cycles of exposure is 2.2% according to the actuarial method. There is no significant difference between NFP users and mixed methods users and also no significant effect of duration of use in the first 5 years of exposure. During "perfect use" the pregnancy rate at 12 months is 0.63%. When only protected intercourse takes place in the fertile phase the pregnancy rate is 0.45%. The symptothermal method of NFP is most unforgiving for imperfect use (unprotected intercourse in the fertile phase). However, it is extremely effective when either abstinence or protected intercourse is used in the fertile phase.

Adult↗