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Biomedical subjects

M Feldman

Publications and source records attributed to M Feldman.

At least 379 records · Page 21Linked to original sources

Inhibition of synthesis of alpha-fetoprotein by glucocorticoids in cultured hepatoma cells.

alpha-Fetoprotein (AFP) synthesis was studied in the presence and absence of glucocorticoids in rat hepatoma Mc-A-RH-7777 cells. Radioimmunoassay of media from cell cultures grown in the presence of glucocorticoid (dexamethasone or cortisol) showed a reduction in AFP, an increase in albumin, and no significant change in transferrin accumulation, as compared to controls. Labeling experiments with L-[35S]methionine indicated that in both cells and media of dexamethasone-treated cultures there was a 50--80% reduction in polypeptide precipitated by anti-AFP serum, as compared with controls; no change was seen in polypeptide precipitated by anti-transferrin serum. Pulse and pulse-chase experiments demonstrated that dexamethasone inhibited the synthesis of AFP but not its secretion. The half-time for secretion of AFP in the presence and absence of dexamethasone was 43 min.

Albumins↗

Effect of bethanechol on gastric acid secretion and serum gastrin concentration after proximal gastric vagotomy.

It has been suggested that maximal acid output decreases after vagotomy as a result of reduced cholinergic activity and that maximal acid secretion can be restored to prevagotomy levels with cholinergic agonists. To test this, a maximally tolerated dose of bethanechol (50 micrograms/kg/hr) or saline was infused intravenously in nine duodenal ulcer patients who had been treated by proximal gastric vagotomy. Bethanechol infusion significantly (p less than 0.05) increased basal acid secretion without affecting basal serum gastrin concentrations. Despite stimulation of basal acid secretion, bethanechol had no significant effect on maximal acid output in response to subcutaneous pentagastrin. Although bethanechol significantly increased maximal acid output in response to subcutaneous histamine, maximal acid secretion in response to histamine (or to pentagastrin) was not restored to the prevagotomy level in any patient. Thus, factors other than loss of cholinergic activity appear to be responsible for the large reduction in maximal secretory capacity after vagotomy.

Adult↗

Effect of exercise on postprandial gastric secretion and emptying in humans.

The effect of strenuous physical exercise on postprandial gastric acid secretion and gastric emptying was evaluated in untrained healthy volunteers. Subjects exercised for 45 min on a stationary bicycle at 50 or 70% of their maximal work load, beginning 45 min after a steak meal. Compared with a control study during which subjects sat on the bicycle without exercising, exercise had no significant effect on the gastric acid secretory response to the meal (control, 31.9 +/- 8.3 mmol/120 min; exercise, 32.2 +/- 7.8 mmol/120 min) or on the amount of nonabsorbable meal marker that emptied from the stomach in 120 min (control, 88 +/- 3%; exercise, 87 +/- 4%). Increases in serum triglyceride levels after the meal were also unaffected by exercise, suggesting that absorption of dietary lipid was unimpaired by exercise. These studies indicate that strenuous exercise shortly after a meal has little effect on postprandial gastric secretory or motor function in humans.

Adult↗

Effect of cephalic-vagal stimulation on insulin, gastric inhibitory polypeptide, and pancreatic polypeptide release in humans.

The purpose of the present study was to determine whether there is a cephalic phase of insulin or gastric inhibitory polypeptide release in man. Seven healthy, normal weight volunteers were sham fed an appetizing steak meal, and serum insulin, gastric inhibitory polypeptide, and pancreatic polypeptide concentrations were measured. A pancreatic polypeptide response to sham feeding was employed as marker of adequate cephalic-vagal stimulation. Although serum pancreatic polypeptide concentrations increased significantly (P less than 0.05) in response to sham feeding, sham feeding had no significant effect on serum insulin and gastric inhibitory polypeptide levels. In addition, sham feeding did not affect insulin or gastric inhibitory polypeptide responses to intragastric glucose, although sham feeding did augment the pancreatic polypeptide response to this meal. These experiments were, therefore, unable to demonstrate insulin or gastric inhibitory polypeptide release in response to cephalic-vagal stimulation in humans.

Adult↗

Adrenergic regulation of distention-induced gastrin release in humans.

To investigate the possible role of adrenergic nerves in neurally mediated gastrin release, we evaluated the effect of selective adrenergic blockade on the serum gastrin response to gastric distention in healthy human subjects. On separate days, 2 mg of propranolol (beta-adrenergic antagonist), 5 mg of phentolamine (alpha-adrenergic antagonist), or saline (control) was injected intravenously just before distending the stomach with 700 ml of isotonic saline. For 30 min following distention, intragastric pH was kept constant at 5.0 by in vivo titration. Propranolol reduced distention-induced gastrin release by approximately 90% (p less than 0.02), whereas phentolamine had no significant effect on the gastrin response to distention. In additional experiments, we evaluated the effect of the same doses of propranolol or phentolamine on the exaggerated gastrin response to gastric distention that occurred during cholinergic blockade with atropine. In the presence of atropine (2.3 microgram/kg i.v.), propranolol significantly (p less than 0.01) reduced distention-induced gastrin release, whereas phentolamine significantly enhanced the gastrin response to distention (p less than 0.01). We conclude that: (1) distention-induced gastrin release was reduced by propranolol, suggesting that gastric distention releases gastrin by a beta-adrenergic mechanism and (2) distention-induced gastrin release was enhanced by phentolamine, but only in the presence of atropine. Thus, adrenergic nerves appear to regulate the gastrin response to gastric distention in humans: beta-adrenergic pathways stimulate gastrin release, and alpha-adrenergic pathways may inhibit gastrin release under certain circumstances.

Adrenergic alpha-Antagonists↗

The in vitro generation of suppressor lymphocytes involves interactions between PNA+ and PNA- thymocyte populations.

Employing cell fractionation with the aid of peanut agglutinin, it was found that at least two subpopulations of T cells are required for the generation of suppressor T lymphocytes in culture. The co-operation of these two subpopulations, the medullary and the cortical types of thymocytes, is required for the induction phase but it apparently plays no role in the expression of the suppressive effect. With the aid of genetic markers, it was found that in medullary-type, cortisone-resistant, PNA-negative T cell was the progenitor of the suppressor lymphocytes, while the cortical type cells performed an accessory (regulatory?) function. Finally, it was observed that allostimulation of T cells in culture give rise to both 'helper' and suppressor cells. The generation of 'helper' lymphocytes requires allostimulation for less than 24 hr while the induction of suppressor cells requires a longer period of stimulation which leads in the end to predominance of the suppressor effect.

Animals↗

An immune response against the alloantigens of the 3LL Lewis lung carcinoma prevents the growth of lung metastases, but not of local allografts.

3LL tumor cells inoculated intra footpad grow locally both in syngeneic and in allogeneic recipients. Yet, spontaneous lung metastases appear only in syngeneic animals or in mice which share with the tumor strain of origin both the D-end of the H-2b haplotype and the genetic background. The lack of lung metastases in allogeneic recipients is not due to tissue restrictions for tumor growth, since intravenous injections of tumor cells resulted in local primary lung tumors. The growth rate of primary intra footpad tumors or pulmonary tumors in syngeneic mice is similar to that in congenic resistant recombinant mice. From a local intra footpad tumor in BALB/c mice, 3LL cells migrate out and reach the lungs but are arrested there, since grafts of lungs from such mice onto (BALB/c X C57BL/6)F1 resulted in tumor growth. Since spontaneous metastases developed in chimeric (C3HeB X C57BL/6)F1----C3HeB mice, it appeared that immunogenetic restrictions prevent the growth of spontaneous 3LL metastases in allogeneic recipients. Further support for the notion of allograft rejection of lung metastases derived from experiments demonstrating the generation of metastases in nu/nu ICR mice but not in nu/+ heterozygous ICR animals. It thus appeared that the local allograft of the 3LL tumor elicits a reaction which prevents the growth of its metastases. This was further supported in experiments in which intravenous inoculation of 3LL cells to allogeneic recipients from which the local tumor was removed did not produce lung tumors.

Animals↗

Androgen-binding protein. Purification from rat epididymis, characterization, and immunocytochemical localization.

Androgen-binding protein (ABP) was purified from caput epididymis of the rat by sequential chromatography on DEAE-Sepharose, hydroxylapatite, dihydrotestosterone-17 beta-hemisuccinyl-1,6-diaminohexane-Sepharose, and Sephadex G-150. The final product migrated as a single band corresponding to a peak of protein-bound [3H]dihydrotestosterone on polyacrylamide gel electrophoresis. A molecular weight of 100,000 was estimated by sedimentation equilibrium. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, subunits of Mr = 47,000 and 41,000 were observed. Amino acid analysis indicated ABP to be rich in leucine while nonpolar aminoacids totaled only 51%. Its carbohydrate content is 25%. Antibodies to purified ABP were raised in a rabbit and evaluated by immunodiffusion, immunoelectrophoresis, binding inhibition, radioimmunoassay, and immunocytochemistry. Immunoperoxidase staining localized ABP in the basal and adluminal regions of seminiferous tubules of rat testis and in secretory granules of cultured Sertoli cells. In principal cells of caput epididymis, ABP is concentrated in the supranuclear region known to contain morphological specializations for absorption. These immunocytochemical results confirm that ABP synthesized and secreted by Sertoli cells in the testis is transported to the epididymal duct via testicular fluid and is taken up by epithelial cells of the proximal segments.

Amino Acids↗

RNA inhibits estrogen receptor binding to DNA.

Cytosol from MTW9 rat mammary tumor contains a high molecular weight inhibitor of estrogen receptor binding to DNA. RNase treatment of crude preparations destroys inhibitory activity, whereas DNase or trypsin treatment are without affect, suggesting that some RNA molecule might be involved; in addition, RNA extracted from tumor cytosol was an effective inhibitor of estrogen receptor binding to DNA. A number of synthetic and natural RNA species were analyzed for inhibitory activity; a definite specificity was observed, with poly(G) > poly(U) > poly(A) or poly(C).

Animals↗

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↗

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↗

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↗