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Biomedical subjects

S Segal

Publications and source records attributed to S Segal.

At least 487 records · Page 27Linked to original sources

The effects of diazene dicarboxylic acid bis-(N, N-dimethylamide) on glycine uptake by newborn renal cortex.

Glycine uptake by newborn rat renal cortical slices in the presence of 2 mM diamide remained unchanged from control value during incubation times up to 30 minutes. Longer exposure to diamide resulted in decreased net uptake. Kinetic analysis of this phenomenon indicated a noncompetitive inhibitory effect of diamide upon the low-affinity glycine uptake system, whereas glycine uptake on the high-affinity system was obliterated. A similar analysis of the diamide effects on adult tissue indicated a noncompetitive inhibition of both the low- and high-affinity glycine transport systems. Diamide did not cause any demonstrable change in glycine efflux from newborn cortical slices. Thus the decreased net uptake we observed in newborn slices in the presence of diamide could be explained solely on the basis of an effect on glycine entry. Simultaneous measurements of intracellular glutathione (GSH) levels in the newborn tissue showed a lack of any direct relationship between the transport effects of diamide and its oxidative effect on reduced glutathione.

Animals↗

Observations on the antigenicity and clinical effects of a candidate antipregnancy vaccine: beta-subunit of human chorionic gonadotropin linked to tetanus toxoid.

Observations on the antibody response and clinical effects of injection of purified beta-subunit of human chorionic gonadotropin covalently linked to tetanous toxoid were made in 15 healthy young women who had previously undergone tubal ligation. Antibodies detectable by radioimmunoassay were found in 14 of the women. Clinical surveillance and immunologic, hematologic, and biochemical tests indicated excellent local and systemic tolerance to the antigen. No significant adverse effects on menstrual function, endocrine status, or health were found.

Antibody Formation↗

Developmental and other characteristics of lysine uptake by rat brain synaptosomes.

Synaptosomes isolated from adult or newborn rat cerebrum take up L-lysine by two saturable systems, one with a high affinity low capacity and the other with a low affinity high capacity. Initial rate of uptake for low lysine concentrations is mort tissue. Analysis of kinetic data indicates that synaptosomes of the newborn have a higher Vmax than those of the adult for high affinity system but adult for high affinity system but adult synaptosomes have a higher Vmax than newborn for low affinity system. At a physiological lysine concentration of 0.5 mM, the calculated contributions of two systems indicate that the adult uptake occurs for about 71% by low affinity system but the newborn utilizes both systems to the same extent. The uptake is sodium independent but pH dependent. Lysine uptake is inhibited by other dibasic amino acids, arginine and ornithine but not cystine. Kinetic analysis indicates that arginine specifically inhibits the high affinity, low Km system for lysine uptake.

Aging↗

The effect of diamide on amino acid transport by rat renal cortex slices.

Diamide directly added to renal cortical slices inhibits the uptake of amino acids. Steady-state kinetic analysis indicates an inhibition of alpha-amino acid influx without effect on efflux. The effect could be reversed by addition of pyruvate to the incubation medium. Although there was a good correlation of the transport effect of diamide with its ability to decrease cellular reduced glutathione concentration, there did not appear to be a necessary connection between them. This was shown by the fact that renal cortical slices stored at 4 degrees C have no alteration in amino acid uptake despite the fact that GSH concentration is as low as that seen with diamide. Diamide was shown to have a direct effect on the uptake of glycine by isolated renal brush border membrane vesicles.

Amino Acids↗

Sodium gradient dependence of proline and glycine uptake in rat renal brush-border membrane vesicles.

The sodium-dependent entry of proline and glycine into rat renal brush-border membrane vesicles was examined. The high Km system for proline shows no sodium dependence. The low Km system for glycine entry is strictly dependent on a Na+ gradient but shows no evidence of the carrier system having any affinity for Na+. The low Km system for proline and high Km system for glycine transport appear to be shared. Both systems are stimulated by a Na+ gradient and appear to have an affinity for the Na+. The effect of decreasing the Na+ concentration in the ionic gradient is to alter the Km for amino acid entry and, at low Na+ concentrations, to inhibit the V for glycine entry.

Animals↗

The synthesis and secretion of human chorionic gonadotropin by tissue slices from first trimester placentas.

Placental tissue slices from first trimester placentas synthesize and secrete proteins labeled by radioactive glucosamine are preferentially secreted as compared to proteins in general. One of the proteins synthesized and secreted is hCG. Processing and secretion of proteins, including hCG, by the tissue slices need a two-hour period. Both secretion and glycosylation of the protein can take place independently of protein synthesis. A method was developed for the specific determination of newly synthesized radioactive hCG in placental tissue.

Chorionic Gonadotropin↗

Characterization of renal defects in dogs with a syndrome similar to the Fanconi syndrome in man.

Ten adult dogs with multiple spontaneous defects of renal tubular reabsorption were studied. Clinical signs included polydipsia, polyuria, and glycosuria for 2 to 12 months. Eight of the dogs were Basenjis. Urinalyses revealed hyposthenuria, glycosuria, and amino aciduria in most dogs. Renal function was normal in 5 dogs and slightly reduced in the remainder. Moderate metabolic acidosis had developed in 3 dogs. Renal clearance studies revealed reduced tubular reabsorption of glucose, phosphate, sodium, potassium, and uric acid. Abnormal glucose tubular maximal curves were found. Results of oral glucose tolerance tests were normal. Two patterns of abnormal amino aciduria were evident: generalized amino aciduria and a pattern similar to that of cystinuria in dogs. Radiography of long bones and bone densitometry did not reveal any skeletal abnormalities. Five of the dogs died within 90 days of diagnosis; death was due to acute renal failure associated with profound dehydration, acidosis, and papillary necrosis. The other dogs remained stable without treatment after 18 months. Histopathology of kidneys did not reveal uniform abnormalities; some dogs had variable and nonspecific changes and others were normal. Electron microscopy did not reveal ultrastructural abnormalities in renal tubular cells. It was concluded that the syndrome in these dogs represents a new entity of renal disease in dogs, similar to idiopathic Fanconi syndrome in man.

Animals↗

An immunoregulatory factor associated with spleen cells from tumor-bearing animals. III. Characterization of the factor's target cells.

An immunoregulatory factor associated with spleen cells from tumor-bearing mice was found to potentiate the generation of antibody-producing cells (APC). In an attempt to characterize the target cell of this enhancing factor (EF), its activity in mice devoid of mature T lymphocytes was tested. Levels of anti-SRBC APC were augmented when EF was injected together with SRBC to nude mice and "B" mice. In addition, EF potentiated the antibody response against the IgM-inducing T-independent pneumococcal plysacchardide SIII antigen. These results suggest that EF most probably exerts its enhancing influence directly on B lymphocytes. In a different line of experiments adoptive secondary responses were performed. Mice were immunized with SRBC as carrier or with the NIP-chicken erythrocytes (as a source of NIP-specific primed B cells) in the presence or absence of EF. Various combinations of spleen cells from the donor immunized mice were transferred in a mixture with NIP-SRBC to lethally irradiated recipient mice, EF did not exert any potentiation effect on helper function, except when primed B cells were used. In contrast, a clear activation or clone expansion of hapten-specific B cells was observed. These findings indicate that the enhancing factor from tumor-bearing animals directly affected the antigenic triggering of B lymphocytes and their subsequent proliferation and differentiation to antibody-producing cells.

Animals↗

L-proline transport by newborn rat kidney brush-border membrane vesicles.

The transport of L-proline was studied in brush-border membrane vesicles isolated from the kidneys of newborn rats. In contrast with the rapid initial uptake with an 'overshoot' observed in adult vesicles, uptake by the newborn vesicle was slow, showed no 'overshoot', and proline continued to accumulate at a time when the adult vesicle had already equilibrated. L-Proline transport in the newborn rat occurs by Na+-dependent and independent mechanisms. There appeared to be essentially no uptake by anti-luminal vesicles isolated from newborn rat kidney. These observations may help to explain the prolinuria that occurs in the newborn animal.

Animals↗

Tumor-associated antigenic differences between the primary and the descendant metastatic tumor cell populations.

The existence of antigenic differences between cell populations in the local growth of the 3LL tumor (L-3LL) and its lung metastases (M-3LL) was studied. Normal C57BL/6 spleen cells sensitized in vitro for 5 days against L-3LL monolayers lysed preferentially L-3LL targets but not M-3LL tumor cell targets. Conversely, anti-M-366-sensitized lymphocytes killed M-3LL targets more efficiently than they killed L-3LL targets. Furthermore, spleen cells from mice bearing subcutaneous L-3LL tumors were significantly more cytotoxic to L-3LL targets than to M-3LL targets and vice versa. M-3LL cells were found also to be more resistant in vitro and in vivo to natural killer cells than were L-3LL tumor cells. M-3LL cells were more resistant than L-3LL cells to hybrid resistant mechanisms when they were inoculated into F1 (C3Heb x C57BL/6) or F1 (BALB/c x C57BL/6) mice. Anti-M-3LL lymphocytes generated both in vitro and in vivo, but not anti-L-3LL lymphocytes, admixed with L-3LL or M-3LL tumor cells and inoculated into footpads of syngeneic recipients suppressed the development of lung metastases. These results suggest that metastatic cells are indeed phenotypic variants of the local growing tumor cell populations. Presumably, these variants are selected for their capacity to home to and grow in the lungs, and for their resistance to specific immune effects initially evoked against the local tumor and to nonspecific natural killer cells. These data may prove to be of importance with respect to any rational approach to the problem of immunotherapy.

Animals↗

Uptake of glycine by human kidney cortex.

The transport of glycine was investigated in histologically normal adult human kidney cortical slices. Uptake occurs against a gradient and shows concentration dependence. Kinetic analysis reveals two systems for transport of glycine with apparent transport Km values of 0.511 and 34.2 mM. Glycine transport on the high-Km system is competitively inhibited by 50 mML-proline. Transport inhibition on the low-Km system could not be directly evaluated, but on theoretic grounds appears not to be inhibited by L-proline or hydroxyproline. Alpha-aminoisobutyric acid, valine, and thioproline are also shown to inhibit glycine uptake. Low medium sodium or anaerobic incubation depress the uptake of glycine. These observations are consistent with previous reports of glycine transport in rat kidney and support the proposals for the mechanism of familial iminoglycinuria based on in vivo investigations.

Adult↗

Male hyperprolactinemia:effects on fertility.

Male hyperprolactinemia was detected in 4% (7 of 171) of infertile men. In seven patients with excessive serum prolactin concentrations, the clinical manifestations were infertility, hypogonadism, impotence, and galactorrhea and the etiologic factors were pituitary adenoma, hypothalamic dysfunction, drug use, and idiopathic. The testes and prostate were small or normal and the semen analysis revealed low semen volume, normal or low sperm count, and normal or impaired sperm motility. The testicular biopsy showed normally preserved seminiferous tubules with normal or decreased spermatogenesis and damaged or fibrotic seminiferous tubules among normal ones. Patients with hyperprolactinemia were investigated by sellar polytomography, visual field examinations, and hormone assays. Treatment with bromocriptine (Parlodel) gave satisfactory results in all patients. The use of bromocriptine with human menopausal gonadotropin and human chorionic gonadotropin was beneficial in treating hypogonadotropic hypogonadism with hyperprolactinemia.

Adult↗