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Biomedical subjects

S Segal

Publications and source records attributed to S Segal.

At least 433 records · Page 24Linked to original sources
PubMed1981

Rapid gas chromatographic-mass spectrometric analysis of [15N]urea: application to human metabolic studies.

A rapid gas chromatographic-mass spectrometric method for [15N]urea analysis is described which is based on the formation of a TFA-urea derivative. The method is extremely sensitive, being capable of detecting less than 0.2 atom % excess [15N]urea in as little as 50 microliter of plasma and 10 microliter of urine with a coefficient of variation of 11%. The method was used to measure in vivo the disappearance of [15N]urea from plasma and the incorporation of [15N]ammonium acetate into [15N]urea. The values obtained for urea pool size and flux are 4.5 +/- 0.30 g nitrogen/total body weight and 16.2 +/- 1.34 g nitrogen per 24 h per 1.73 m2. Following the ingestion of [15N]ammonium acetate nearly 90% of the 15N label was incorporated into [15N]urea by 30 min.

Adult↗
PubMed1981

Effects of cysteamine therapy in nephropathic cystinosis.

We studied the effects of cysteamine in five children with nephropathic cystinosis who were treated for up to 30 months. Cysteamine caused a decline in leukocyte cystine levels to the range seen in clinically unaffected heterozygotes; both plasma and urinary cystine diminished by more than half. Therapy had no effect on progressively declining creatinine clearance in three patients, but improvement occurred in the other two. Phosphaturia, glycosuria, aminociduria, and organic aciduria did not improve in any of the patients. Both blood lactate and the lactate pyruvate ratio were diminished. Growth velocity, which was abnormal in four of the five children, did not improve. No major side effects were noted. Therapy with cysteamine caused a consistent, dose-related decline in levels of cystine in leukocytes and in extracellular fluid, caused no improvement so far in renal tubular function or growth velocity, and improved creatinine clearance in some patients.

Amino Acids↗
PubMed1981

Involvement of the spleen in murine B cell differentiation.

Experiments were performed to study the influence of neonatal and adult splenectomy on B cell differentiation in mice. Lymph node cells of both groups were found to contain a significantly higher proportion of Ig-bearing cells. Moreover, these cells expressed a higher density of membrane Ig and a higher IgM/IgD ratio. In addition, the response of these cells to different polyclonal B cell activators, especially dextran sulfate, was much higher than the response of the sham-operated controls. Similar experiments were carried out in splenectomized and control animals that were lethally irradiated and reconstituted with different hemopoietic cell sources. The same pattern of results was obtained, except when reconstituting the irradiated animals with fetal liver cells. These experiments, which were performed at long time intervals post splenectomy, show that in the absence of the spleen, there is an accumulation of less mature B cells in the periphery implying an active role of the spleen in at least certain differentiation steps of the B cell lineage.

Animals↗
PubMed1981

The peritoneal antigen-presenting macrophage: control and immunogenic properties of distinct subpopulations.

The control of the immunogenic antigen-presenting capacity of different subpopulations of thioglycollate-induced peritoneal macrophages had been investigated. The experiments revealed the existence of two major subpopulations of macrophages, only one of which was highly efficient in educating antigen-specific T cells. The other subpopulation, while highly phagocytic, was devoid of antigen-presenting capacity. Further analysis, using specific antisera directed at H-2I region gene products, revealed that the immunogenic antigen-presenting population expressed H-2I region-controlled membrane antigens. Searching for cellular elements which control the differentiation of this antigen-presenting macrophage subpopulation, it was found that its function was strictly controlled by T cells. T cell-deficient mice (nu/nu) failed to generate a functional antigen-presenting macrophage subpopulation. Transplantation of mature T lymphocytes to T cell-deprived mice restored the immunogenic function of their antigen-presenting macrophage subpopulation. Transplantation of mature T lymphocytes to T cell-deprived mice restored the immunogenic function of their antigen-presenting macrophages. The results obtained suggest the existence of heterogeneity of functions among macrophage subpopulations and add a new regulatory function for T cells.

Animals↗
PubMed1981

Involvement of the spleen in the control of the immunogenic and phagocytic function of thioglycollate-induced macrophages.

The immunogenic capacity of thioglycollate-induced peritoneal macrophages of adult splenectomized animals was compared to that of macrophages of sham-operated controls. Macrophages from splenectomized animals were found to be impaired in their function as antigen-presenting cells, both in the education of virgin initiator T lymphocytes and in the stimulation of antigen-specific T memory cells. Macrophages from splenectomized animals were also severely impaired in their phagocytic capacity, as assessed in an opsonin-dependent bacterial phagocytosis assay. However, they were not impaired in their ability to pinocytose soluble keyhole limpet hemocyanin. These results indicate that the spleen may play a decisive role in controlling the differentiation of peritoneal macrophages.

Animals↗
PubMed1981

Defective induction of antigen-reactive proliferating T cells in B cell-deprived mice.

Mice were injected from day of birth onward with rabbit anti-mouse IgM antiserum or purified rabbit anti-mouse IgM antibodies. These mice completely lacked Ig-positive cells or serum Ig, as analyzed by specific fluoresceinated antibodies on the fluorescence-activated cell sorter (FACS-II), by polyclonal B cell mitogens and by specific precipitation in agar. These animals were then primed in vivo by antigen emulsified in complete Freund's adjuvant, and, subsequently, their draining lymph nodes were tested for their T cell proliferative responses in vitro, to the relevant antigen and were found to be severely impaired. However, the antigen-presenting capacity of both spleen cells and thioglycollate-induced peritoneal cells was found to be intact.

Animals↗
PubMed1981

Cysteamine inhibition of [15N]-glycine turnover in cystinosis and of glycine cleavage system in vitro.

In order to clarify the hyperglycinemic effect of cysteamine treatment in children with nephropathic cystinosis, we measured [15N]-glycine turnover in three affected patients. Administration of cysteamine lowered the glycine flux and the glycine metabolic clearance rate but did not alter the glycine pool size. Formation of [15N]-serine from [15N]-glycine was lower in untreated patients than in control subjects and was reduced still further by cysteamine. Studies in vitro with isolated rat liver mitochondria and acetone extracts of mitochondria indicated that even low cysteamine concentrations (0.1 mM) inhibited the glycine cleavage system in both the direction of glycine oxidation and glycine synthesis. Cysteamine was a more potent inhibitor of the glycine cleavage system than any other sulfhydryl containing compound. Although no ill effects of cysteamine treatment were immediately apparent, patients receiving cysteamine should be monitored carefully for the appearance of any neurologic symptoms which might be referable to inhibition of the glycine cleavage system.

Coenzyme A↗
PubMed1981

Microsurgical vasovasostomy: immunologic consequences and subsequent fertility.

Fifty-five men have undergone microsurgical vasovasostomy with at least a 1-year follow-up. Serum samples from these men were obtained in the preoperative and postoperative periods, and titers of agglutinating and immobilizing antibodies were measured and evaluated in relationship to subsequent fertility. Of the 35 patients in whom adequate serum and semen samples were obtained over a period of 1 year, 17 men proved their fertility and 18 patients in the allotted time span had not yet fathered any children. No statistically significant difference in the level of antibody titers could be found between the fertile group and the infertile group. Seminal antibody titers were determined in 25 men. Five of these men have thus for impregnated their wives. Only a small number of men were found to have positive titers for agglutinating and/or immobilizing antibodies in their semen. The presence or absence of spermagglutinating and/or sperm-immobilizing antibodies in the sera of men who have undergone vasectomy reversal does not seem to interfere with subsequent fertility.

Antibodies↗
PubMed1981

Surgical correction of lateralized eardrum.

The complication of retraction and lateralization of the graft after a tympanoplasty operation is described, and the underlying mechanism discussed. This complication occurs mainly when using the overlay procedure and causes a severe conductive hearing loss. A surgical technique for correcting this problem is described. It consists of removing all of the former graft, positioning the new graft medial to the eardrum remnants and covering the denuded ear canal bone with split-thickness skin graft. The results of 7 cases successfully treated by the technique described are presented.

Hearing Loss, Conductive↗
PubMed1981

Proline and glucose transport by renal membranes from dogs with spontaneous idiopathic Fanconi syndrome.

The uptake of proline and glucose by renal brush border membrane vesicles isolated from Basenji dogs exhibiting a spontaneous Fanconi syndrome was examined. The magnitude of the 1-min, Na+-gradient uptake of proline (0.02 mM) and glucose (1.0 mM) by vesicles from affected dog kidney was lower than normal. Concentration-dependent 15-sec uptake in vesicles from normal and affected dogs reveals a two-component transport system for proline and glucose. Kinetic analysis shows altered Km and Vmax values for both proline and glucose transport in the affected dogs. The data suggest that, in this model of Fanconi syndrome, the defective renal reabsorption of proline and glucose is associated with an alteration of luminal transport system.

Animals↗
PubMed1981

H-2K region-controlled products of the murine major histocompatibility complex differ in their immunogenic capacity when expressed on different tissues.

Reciprocal skin grafts between the C57BL/6 (H-2b) mice and the mutant strain B6.C-H(Z1) (H-2ba), which differ only in a point mutation in the K region of the major histocompatibility complex, elicit rejection reactions similar to those elicited by skin allografts incompatible at multiple loci. Thyroid grafts in the same combinations are not rejected. Analyzing the immunogenicity of H(Z1) skin and thyroid tissues, we found that secondary H(Z1) thyroid grafts were rejected by C57BL/6 mice which had rejected H(Z1) skin tissue. On the other hand, pregrafting of C57BL/6 mice with H(Z1) thyroid did not induce a rejection reaction against a second-set H(Z1) thyroid transplant. These results indicate that gene products of the K region are expressed on thyroid cells and are recognized by memory lymphocytes induced by the H(Z1) skin. Yet, unlike the skin cells, the thyroid expressed H-2k-associated determinants in a nonimmunogenic form which can induce neither an actual rejection nor a state of memory.

Animals↗
PubMed1981

Sex-associated differences in the immune response against fetal major histocompatibility antigens.

Alloantibodies against H-2b and H-2k haplotypes were produced in C57BL/6J and C3H female and male mice in response to transplantation of F1 fetal tissue (bone) or adult F1 cells (spleen). Testing IgG1 and IgG2 antibodies by means of the fluorescence-activated cell sorter (FACS II), we found no differences between males and females in the isotype content of antisera produced against spleen cells from adult donors. In contrast, striking sex-associated differences were found in the isotypes produced against fetal allografts: females produced much more IgG1 than males, although they produced comparable amounts of IgG2. Hence, it appears that females differ from males in their humoral alloreactivity against major histocompatibility complex (MHC) gene products expressed on fetal cells. Such MHC antigens expressed on fetal tissues seem to generate different immune signals than the MHC antigens expressed on adult cells. These observations might be of relevance to the biological role played by the IgG1 alloantibodies produced during pregnancy against the MHC alloantigens of the fetus.

Animals↗
PubMed1981

Experimental galactose toxicity: effects on synaptosomal phosphatidylinositol metabolism.

Experimental galactose toxicity was induced by weaning rats onto an isocaloric 40% galactose diet. Synaptosomes were prepared from cerebra of rats at 2-9 weeks post-weaning and incubated with [33P][i and myo-[2-3H]inositol in the presence or absence of 0.2 mM-acetylcholine. The acetylcholine-stimulated [33P]Pi labeling of phosphatidylinositol and the changes in amounts of phosphatidylinositol were similar in the normal and galactose-toxic rats; however, acetylcholine-stimulated myo-[2-3H]inositol labeling of phosphatidylinositol was markedly decreased in the galactose-toxic rats. The impairment of acetylcholine-stimulated myo-[2-3H]inositol incorporation into phosphatidylinositol observed after 2 weeks on the diet did not vary after more prolonged exposure to galactose.

Acetylcholine↗
PubMed1981

Changing activities of galactose-metabolizing enzymes during perfusion of suckling-rat liver.

The specific activities of the galactose-metabolizing enzymes, galactokinase (EC 2.7.1.6), galactose-1-phosphate uridyltransferase (EC 2.7.7.12), and UDPgalactose 4-epimerase (EC 5.1.3.2), in suckling-rat livers perfused for 90 min with 1 and 4 mM galactose fluctuate significantly with a different pattern of change for each enzyme. Perfusion for 30 min with galactose resulted in a significant increase of transferase specific activity followed by a precipitous decline to about one-fifth of the activity in unperfused liver at 90 min. The increase in transferase activity was also observed when D-glucose was perfused but not when L-glucose, D-fructose, D-xylose, or D-ribose was added to the perfusate. No such changes in transferase activity were observed when adult-rat liver was perfused with galactose. Epimerase activity in the suckling-rat liver was relatively low, and the changes in its activity correlated best with the uptake rate of galactose. The perfused suckling-rat liver may provide a model system for examination of factors that modulate the specific activity of galactose-metabolizing enzymes and effect the metabolism of galactose.

Animals↗