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Biomedical subjects

S Segal

Publications and source records attributed to S Segal.

At least 343 records · Page 19Linked to original sources

Sleep and breathing in sleep in children with breath-holding spells.

Sleep recordings were obtained in 21 children with breath-holding spells to investigate the possible existence of breathing disorders in sleep. Sleep recordings revealed an increased amount of wake time within sleep and sleep stage 1, and decreased amounts of stages 2 and REM. None of the children had more than 20 apneic episodes during sleep. These findings support the hypothesis that breath-holding spells are a functional disturbance of psychological nature only.

Child↗

Developmental aspects of sugar transport by isolated dog renal cortical tubules.

alpha-Methyl-D-glucoside (AMG) uptake was examined in isolated renal cortical tubules from newborn, 3-month-old, and adult dogs. All three age groups demonstrated active sugar transport. The initial rate of AMG uptake was similar in the 3-month-old and adult tubules which was twice that of the newborn. At steady-state, the adult and newborn tubules had achieved a similar intracellular AMG concentration which was 45% greater than that of the 3-month-old. Determination of the flux constants of these uptake patterns revealed that there was an age-dependent increase in both the net flux and the fractional influx rate constant. However, the 3-month-old had the highest fractional efflux rate constant and the newborn the lowest value with the adult in between. Kinetic analysis of AMG uptake showed a single saturable transport system for each age group. The newborn and adult had similar Km values but the 3-month-old had a value that was 60% higher. The 3-month-old tubules had the highest Vmax and the newborn tubules the lowest with the adult value in between. AMG uptake by tubules from each age group demonstrated a similar pattern of inhibition in a low sodium buffer and by glucose and phlorizin. This indicated that, aside from kinetic changes with maturation, the saturable transport system for AMG is similar in each age group.

Aging↗

Comparison of the in vitro sperm penetration test using human cervical mucus and bovine estrus cervical mucus with the postcoital test.

The objective of this study was to determine how well bovine estrus cervical mucus could be substituted for human cervical mucus in the in vitro sperm penetration test (SPT) and how well the SPT compares with the postcoital test (PCT). The subjects were couples chosen at random from our infertility clinic population. The complete infertility evaluation of these couples included a PCT performed at the time of anticipated ovulation. Human cervical mucus quality was assessed using a scoring system which evaluated amount, spinnbarkeit, ferning, viscosity, and cellularity. SPT's were performed in flat capillary tubes filled with cervical mucus and exposed to semen samples for 90 minutes. Thirty-five couples had SPT's performed with wife's mucus and bovine mucus. Test results showed that PCT results correlated significantly with the SPT (P 0.02) but r was low (r = 0.37). The cervical mucus score correlated well with the SPT (P 0.001, r = 0.52) but less well with the PCT (P 0.03, r = .30). It is concluded that the SPT performed with either wife's mucus or bovine mucus is not an adequate substitute for the PCT but provides complementary information.

Animals↗

Corpus luteum function in ectopic pregnancy.

Serum beta HCG, progesterone, and 17 alpha hydroxy progesterone values were determined in cases of ectopic pregnancy. They were found to be significantly lower than in normal intrauterine pregnancies of the same gestational age. No correlation was found between serum beta HCG and 17 hydroxy progesterone values or between serum progesterone and 17 hydroxy progesterone values. Our results tend to support the theory that a normal feto placental unit is needed for the preservation of the function of the corpus luteum.

17-alpha-Hydroxyprogesterone↗

Sex-associated differences in the regulation of immune responses controlled by the MHC of the mouse.

The immunologic potential of T lymphocytes and antigen-presenting cells (APC) from male and female mice were compared. Lymphocytes from female mice or from male mice that cannot produce and respond to testosterone (Tfm/y) were more reactive than male lymphocytes to alloantigens in MLR. Spleen cells from Tfm/y mice equipped with estrogen implants showed a higher responsiveness than control Tfm/y to alloantigens. The removal of suppressive adherent cells or the addition of T cell growth factor (TCGF) enhanced the proliferative activity of the cells in the MLR. The responsiveness of female cells to alloantigens, however, remained superior to that observed in male cells. Similarly, in the presence of TCGF, thymocytes from female mice react more effectively than male cells in MLR. In addition, Con A-stimulated spleen cells from female mice produce more interleukin 2 (IL 2) than do spleen cells from males or female mice treated with testosterone. Lymphocytes from immunized mice were tested for their ability to respond to soluble antigens (KLH and OVA) in vitro. Again, female immunocompetent cells respond more vigorously than male cells or cells originating in female mice with testosterone implants. APC from female spleen were more efficient than male APC in initiating a secondary response in primed lymphocytes from either males or female mice. Moreover, castration of male mice enhanced, and treatment of female mice with androgen reduced, the efficiency of antigen presentation. In conclusion, these data suggest that female cells are superior to male cells in immunologic functions that are known to be associated with reactions to and recognition of histocompatibility antigens, i.e., antigen presentation and MLR. Furthermore, our present data indicate that the differential reactivity of immunocytes between male and female mice depends on the hormonal balance of the animal.

Animals↗

Radiosensitivity of isolated subsets of human lymphocytes (E+, OKT4+, OKT8+): protective role of monocytes and monokines.

The sensitivity of human peripheral blood T lymphoid populations to 60Co ionizing radiation was investigated. Dose-response values were determined for populations that are commonly identified by their ability to form spontaneous rosettes with sheep red blood cells (E+ cells), helper T lymphocytes (OKT4+ cells) and suppressor T lymphocytes (OKT8+ cells). OKT4+ and OKT8+ T cell subsets were negatively selected by complement (C)-mediated cytolysis using the C fixing OKT4 and OKT8 monoclonal antibodies (MoAb). The irradiation-induced damage was assessed by the lymphoblast transformation test, using the polyclonal T cell mitogen, phytohaemagglutinin (PHA) and the OKT3 MoAb. (The OKT3 antibodies are mitogenic for T cells only in the presence of monocytes). No significant differences were evident between dose-response values of E+, OKT4+ and OKT8+ lymphoid subpopulations when using PHA as a mitogen. On the other hand, when OKT3 was used to trigger resting irradiated peripheral blood T lymphocytes, e.g. E+ cells, OKT3 stimulated T cells proved to be markedly radioresistant as compared to PHA stimulated cell cultures. This was found to result from the fact that purified T cell cultures were co-cultured with non-irradiated monocytes when OKT3 was employed as a motogen. Similarly co-culturing of irradiated E+, OKT4+ and OKT8+ cells with non-irradiated autologus monocytes partially corrected the irradiation damage, regardless of the mitogen employed. More important, however, was the observation that macrophage derived supernatants containing (interleukin-1) IL-1 could confer a high degree of radioprotection on irradiated E+ cells. It is concluded that monocytes and monocyte products partially protect against irradiation damage.

Antibodies, Monoclonal↗

Loss of the H-2.33 private specificity by 3LL tumor cells correlates with the tumor potential to metastasize across the H-2K region genetic barriers.

Grafts of the metastatic 3LL Lewis lung carcinoma result in pulmonary metastases in mouse strains which share with the tumor strain of origin (C57BL/6, H-2b) the non-H-2 background genes and the H-2D/H-2L region of the major histocompatibility complex. Lung metastases across H-2K region disparities correlated with low expression of H-2Kb-encoded molecule on the tumor cell surface. We tested whether the 3LL tumor cells lack H-2Kb private and/or public specificities by staining 3LL tumor cells and spleen cells of different recombinant mouse strains with H-2d anti-H-2b and anti-3LL antisera, respectively, following absorption of the antisera on spleen cells from various recombinant mouse strains. The data demonstrated weak expression of H-2Kb public specificities (which could represent H-2Db/H-2Kb biregional encoded molecules) and a complete lack of expression of the H-2.33 H-2Kb private specificity by 3LL tumor cells. The findings provide a possible explanation for the 3LL metastatic potential across H-2Kb region disparities.

Animals↗

Glycogen storage disease: effects of glucose infusions on [15N]glycine kinetics and nitrogen metabolism.

The effects of intragastric glucose infusions on [15N]glycine kinetics and whole body protein turnover were investigated in four children with type I and two children with type III glycogen storage disease. Either fasting or the administration of insufficient glucose was associated with a diminution in the glycine pool size relative to values observed when patients received adequate glucose. The cause of the smaller pool size was an increased fractional glycine turnover. Simultaneous determination of whole body protein turnover, using a stochastic model based on [15N]urea excretion, showed higher rates of protein synthesis, nitrogen flux, net tissue protein retention, and reutilization of amino acid nitrogen derived from protein catabolism, in patients receiving sufficient exogenous glucose. Depletion of amino acid pools, presumably because of intensive utilization of these gluconeogenic precursors when inadequate glucose is administered, was associated with a lower rate of whole body protein synthesis.

Adolescent↗

Macrophage-hybridomas: generation, structure, and function.

We report the generation of macrophage-hybridomas, obtained by somatic cell fusion between macrophage-enriched C3H.eB spleen cell population, and a drug-resistant MPC-11 myeloma cell line, designated as 4T00.1L1 clone. Screening for hybridomas possessing macrophage properties was carried out by assaying the presence of two macrophage-specific enzymes: lysozyme and nonspecific esterase. Two hybridomas, E2-7 and E2-10, were selected for further studies. We found that clones of E2-7 (E2-7.7) did not express Fc receptors but possessed cell-surface Ia molecules. In contrast, clones of E2-10 (E2-10.20) possessed Fc receptors but were devoid of Ia molecules. E2-7.7 did, however, express Fc receptors after mitomycin treatment, whereas E2-10.20 eliminated the expression of Fc receptors after treatment with mitomycin C. Opsonized erythrocytes were phagocytized by E2-10.20 cells, but not by E2-7.7. Phagocytosis was thus correlated with the possession of Fc receptors. Testing the response of KLH-primed lymph node cells to KLH-pulsed hybridoma cells, we found that E2-7.7 cells caused antigen-specific lymphoproliferative response, whereas E2-10.20 did not. Thus, antigens could be presented by E2-7.7 but not by E2-10.20 cells. The response was shown to be mediated by T but not by B lymphocytes. The difference in antigen-presenting capacity could not be attributed to differences in antigen uptake by the different hybridomas, because the two hybridomas manifested the same level of pinocytosis. Both hybridomas produced IL1. The differences in the properties of the two hybridomas may indicate that the normal partners represent two distinct subpopulations of macrophages. The segregation of functional properties among the hybridoma clones may lead to a clarification of the dependence of distinct functions on defined molecular structures.

Animals↗

The effect of papain upon proline and sodium transport of rat renal brush-border membrane vesicles.

Treatment of renal brush-border membrane vesicles with papain resulted in the removal of the activity of maltase, gamma-glutamyl transpeptidase and leucine aminopeptidase by 85, 50 and 75%, respectively. Stripping of these membrane enzyme activities constituted about 2% of the total membrane proteins and resulted in a widespread diminution in the ability of a variety of amino acids and sugars to be taken up by the membrane vesicles which remained osmotically responsive. Kinetic analysis of the uptake of proline, which was shown previously to be transported by both sodium-dependent and sodium-independent systems, revealed that the Vmax for the sodium-dependent system and Km for the sodium-independent system were halved, but other parameters were not affected indicating that the papain treatment altered sodium-gradient-stimulated entry and the affinity of the sodium-gradient-independent system for proline. Experiments on sodium entry and efflux demonstrate a marked enhancement of flux, so that equilibration of the sodium gradient occurred about 5-times more rapidly than in untreated vesicles. This occurred without any change in the osmotic properties of the vesicle with regard to sodium or amino acid uptake. Studies of fluorescence polarization suggest that incubation with papain does not alter the lipid domains of the membrane.

Acyltransferases↗

[15N] leucine as a source of [15N] glutamate in organotypic cerebellar explants.

Approximately 26.0% of the [15N] glutamate and [alpha 15N] glutamine formed in organotypic cerebellar explants was derived from [15N] leucine. Approximately 14.0% of the 15NH3 and [amide 15N] glutamine synthesized came from leucine nitrogen. Another 4.0% of the alpha nitrogen of both glutamate and glutamine was derived from [15N] valine. These results suggest that branched-chain amino acids, particularly leucine, may be important for the synthesis of glutamic acid by the brain.

Amino Acids↗

Peptide fragments from the tuftsin containing domain of immunoglobulin G synthesis and biological activity.

Peptides corresponding to sequences of the Fc-portion of immunoglobulin G (IgG) surrounding and containing the tuftsin molecule were synthesized. The compounds were assayed for their ability to compete with [3H-Arg4]tuftsin in binding to mouse peritoneal macrophages and to stimulate the cell's capacity to phagocytize. Despite the sensitivity that tuftsin has demonstrated to various chemical modifications and structural alterations which usually cause reduction or total loss of biological activity, IgG-related analogs possess potent tuftsin-like activity. The activity is not caused by enzymatic breakdown and release of tuftsin. The fact that the elongated tuftsin analogs can specifically be attached to and activate macrophages may indicate a possible connection between Fc and tuftsin's receptors.

Amino Acid Sequence↗

MHC imbalance and metastatic spread in Lewis lung carcinoma clones.

Imbalance in the Kb and Db region encoded molecules is observed in Lewis lung carcinoma clones. The uncloned metastatic population and the D122 high-metastatic clone show no expression of H-2Kb products, while the nonmetastatic A9 clone expresses Kb products. Twenty-nine new subclones of 3LL and A9 were analyzed for D-end and K-end membrane expression, primary growth rate and metastatic spread. We show that the imbalance in H-2Kb to H-2Db is correlated with metastatic properties of a given clone, but local tumor growth is not. A "low Kb/low Db" phenotype is nonmetastatic as is a "high Kb/high Db" phenotype; a "low Kb/high Db" is highly metastatic and a "medium Kb/high Db" is moderately metastatic. We find support for this notion of imbalance in experiments on MHC modulation by interferon and retinoic acid. Interferon increases both Kb and Db expression of A9 and D122 clones yet the net increase of Db was greater than Kb. This was associated with an increase in metastasis formation. Retinoic acid increases the expression of the Db gene product on the nonmetastatic A9, clone, without apparent changes in Kb expression. This treatment shifts the A9 to a high-metastatic phenotype. The significance of this imbalance to the tumor--host relationship is discussed.

Animals↗

Renal brush-border-membrane vesicles prepared from newborn rats by free-flow electrophoresis and their proline uptake.

A method for the isolation of brush-border membranes from newborn-rat kidney, employing centrifugation and free-flow electrophoresis, is described. The composition and purity of the preparation was assessed by determination of enzyme activities specific for various cellular membranes. Free-flow electrophoresis resolves the newborn-rat renal membrane suspension into two populations of alkaline phosphatase-enriched brush-border membranes, designated 'A' and 'B', with the A peak also showing activity of (Na+ + K+)-stimulated ATPase, the basolateral membrane marker enzyme, whereas those of the B peak were enriched 11-fold in alkaline phosphatase and substantially decreased in (Na+ + K+)-stimulated ATPase activity. Membranes in the A peak showed a 7-fold enrichment of alkaline phosphatase, and (Na+ + K+)-stimulated ATPase activity similar to that of the original homogenate. Proline uptake employed to assess osmotic dependency revealed 7% binding of proline to the B vesicles and 31% to the A vesicles. This contrasts with 60% proline binding to vesicles prepared by centrifugation alone. Unlike vesicles from adult animals, proline uptake by B vesicles did not show an Na+-stimulated overshoot, but did exhibit an Na+-gradient enhanced rate of early proline entry. proline entry.

Animals↗

Effect of acidosis on glutamine transport by isolated rat renal brush-border and basolateral-membrane vesicles.

Glutamine uptake was examined in isolated renal brush-border and basolateral-membrane vesicles from control and acidotic rats. In brush-border vesicles from acidotic animals, there was a significant increase in the initial rate of glutamine uptake compared with that in controls. Lowering the pH of the medium increased the initial rate of glutamine uptake in brush-border vesicles from acidotic, but not from control, rats. In brush-border vesicles from both groups of animals, two saturable transport systems mediated glutamine uptake. There was a 2-fold increase in the Vmax. of the low-affinity high-capacity system in the brush-border vesicles from the acidotic animals compared with that from control animals, with no alteration in the other kinetic parameters. There was no difference in glutamine uptake by the two saturable transport systems in basolateral vesicles from control and acidotic animals. Lowering the incubation-medium pH increased the uptake of glutamine by basolateral vesicles from both control and acidotic rats to a similar extent. The data indicate that during acidosis there are alterations in glutamine transport by both the basolateral and brush-border membrane which could enhance its uptake by the renal-tubule cell for use in ammoniagenesis.

Acidosis↗

CMP-dependent phosphatidylinositol:myo-inositol exchange activity in isolated nerve-endings.

Greatly enhanced manganese-dependent phosphatidylinositol:myo-inositol exchange activity was observed when isolated, intact nerve-endings were incubated with the nucleotide, CMP, suggesting that the enzyme, CDP-diglyceride:inositol phosphatidyl transferase, catalyzes this exchange. CMP, at 10 microM, produced as much myo-[2-3H] inositol incorporation into phosphatidylinositol as did 1 mM. This CMP-stimulated exchange activity may reside on the plasma membrane.

Animals↗

Handling of L-[35S]cystine by cysteamine-pretreated cystinotic and normal fibroblasts.

In short incubations with 0.1 mM L-[35S]cystine in phosphate-buffered saline medium, and long incubations with label in complete minimum Eagle's medium with Earle salts, cystine-depleted cystinotic cells reaccumulate labeled cystine more rapidly than pretreated normal cells. Cysteamine pretreatment of both normal and cystinotic cells resulted in an initial increased conversion of exogenous cystine to intracellular cysteine. In 24-h incubations in complete medium, cysteamine-pretreated cells showed enhanced conversion of 0.1 mM L-[35S]cystine to cysteine and reduced glutathione. Addition of cycloheximide to the incubation media decreased the incorporation of 35S into cellular protein by more than 90% but did not affect the accumulation of intracellular labeled cystine in cystinotic cells. Therefore, the incorporation and release of cystine from protein is not an obligatory source of accumulated cystine and we speculate that there may be early extralysosomal entrapment of cystine in cystinotic cells.

Cell Line↗