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Biomedical subjects

M Feldman

Publications and source records attributed to M Feldman.

At least 451 records · Page 25Linked to original sources
PubMed1979

Comparison of acid secretion rates measured by gastric aspiration and by in vivo intragastric titration in healthy human subjects.

In nine healthy subjects acid secretion rates, measured first by gastric aspiration and then by in vivo intragastric titration to pH 5, were compared. In vivo intragastric titration was initiated by instilling 50, 100, or 700 ml saline (pH 5) into the stomach, followed by a continuous intragastric saline infusion at 3.3 ml/min. Irrespective of the volume of saline used to initiate in vivo intragastric titration, acid secretion rates during titration were two to three times greater than secretion rates during gastric aspiration (P less than 0.005). This difference was not due to transpyloric acid losses during aspiration, since such losses were corrected for by nonabsorbable marker recovery; nor was the difference due to a higher intragastric pH during in vivo titration, since significant differences in acid secretion rates between aspiration and titration persisted when in vivo titration was performed at an acid pH. These findings suggest that in vivo intragastric titration leads to higher measured acid secretory rates than gastric aspiration because the titration method is associated with gastric distention and even small degrees of gastric distention stimulate gastric acid secretion.

Adult↗
PubMed1979

Effect of vagotomy in Zollinger-Ellison syndrome.

We evaluated the effect of vagotomy on gastric acid secretion and the clinical course in 3 patients with Zollinger-Ellison syndrome. Basal acid hypersecretion was reduced by 49, 86, and 96%, and peak acid output in response to pentagastrin was reduced by 36, 39, and 71% in the 3 patients. In one patient, 300 mg cimetidine reduced basal acid secretion from 65 to 20 meq/hr before vagotomy; whereas after vagotomy basal acid secretion was reduced from 36 to 0.6 meq/hr by the same dose of cimetidine. One patient has required no antisecretory therapy for 14 yr, whereas 2 patients have also been treated with cimetidine with excellent results. We conclude that vagotomy facilitates control of acid secretion in Zollinger-Ellison syndrome, and we recommend vagotomy and cimetidine rather than total gastrectomy or cimetidine alone for the management of these patients. This combined surgical and medical approach should also allow discovery and removal of isolated tumors in about 10% of patients.

Adult↗
PubMed1979

Reduction of twenty-four-hour gastric acidity with combination drug therapy in patients with duodenal ulcer.

Four "extra-effort" drug regimens were tested to determine which most nearly eliminated 24-hr gastric acidity in 8 patients with duodenal ulcer. The regimens included two 300 mg cimetidine tablets with meals and at bedtime; one 300 mg cimetidine tablet plus an anticholinergic drug with meals and at bedtime; 300 mg cimetidine with meals and at bedtime plus liquid antacid 1 and 3 hr after meals and at bedtime; and 300 mg cimetidine, an anticholinergic drug, and antacid, taken simultaneously as each meal was finished and at bedtime. No regimen completely eliminated gastric acidity. However, compared to standard cimetidine therapy (300 mg four times daily) which led to a median 24-hr pH of 2.6, each "extra-effort" regimen except cimetidine plus an anticholinergic was significantly better in reducing gastric acidity. During the daytime hours, cimetidine with meals plus antacid 1 and 3 hr after meals was most effective (median pH 5.0). However, the more convenient regimen of cimetidine, an anticholinergic drug, and antacid was almost as effective (median pH 4.3). None of the "extra-effort" regimens was significantly more effective than standard cimetidine therapy during the hours of sleep.

Adult↗
PubMed1978

An immunoregulatory factor associated with spleen cells from tumor-bearing animals. I. Effect on tumor growth and antibody production.

An immunopotentiating factor associated with spleen cells of C57BL/6J mice bearing the 3LL tumor is described. Supernatants of cultured spleen cells from tumor-bearing mice (TBM) augmented the generation of both 19S and 7S antibody-producing cells, when injected with sheep erythrocytes into syngeneic C57BL/6J mice. The enhancing supernatant acted both as a polyclonal activator, when injected in the absence of antigen, and as a potentiator of specific antigen-dependent humoral immune responses, when injected in the presence of antigen. It was found to augment induction of specific memory, but not memory expression. Concomitantly with their influence on humoral immune responses, TBM spleen cell supernatants enhanced tumor growth when injected, mixed with 3LL tumor cells, into syngeneic recipients. The secretion of a factor which augments antibody production was not confined to the 3LL tumor system. Spleen supernatants of C47BL mice carrying the B16 melanoma and those of C3H mice carrying the KHT sarcoma had a similar effect on antibody production. These findings suggest that an immunoregulatory factor(s) appears in spleen cells of TBM as a result of their interaction with the neoplastic tissue. This factor can potentiate production of antibodies, possibly also against tumor-associated antigens. The relevance of the immunopotentiating effects of such factor(s) to tumor growth is discussed.

Animals↗
PubMed1978

Specific cytotoxic lymphocytes against syngeneic tumors are generated in culture in the presence of syngeneic, but not xenogeneic, serum.

Experiments were performed to test the effect of xenogeneic (fetal calf) serum (FCS) , as compared to syngeneic mouse serum (SMS) on the generation in culture of specific cytotoxic lymphocytes (CL) against syngeneic tumors. Sensitization in FCS against 3LL tumor cells resulted in CL cross-reacting with B-16 tumor cells and vice versa. Anti-syngeneic fibroblast CL also cross-reacted with 3LL. Such cross-reactivities were shown to be derived from CL directed against FCS determinants. In contrast, sensitization in the presence of SMS resulted in CL directed against tumor-specific antigens. Anti-3LL generated in SMS lysed 3LL targets but not B-16, and anti-B-16 lysed B-16 but not 3LL. The two types of CL had two distinct reactivities in vivo. Anti-3LL CL generated in FCS enhanced tumor growth in vivo, whereas anti-3LL CL generated in SMS had an inhibiting effect on the growth of tumor cells. These results indicate that the application of syngeneic serum during in vitro sensitization against syngeneic tumors may open up new possibilities for the analysis of tumor-specific antigens and for eliciting specific immune reactions against such antigens.

Animals↗
PubMed1978

A randomized trial of preoperative radiotherapy in cancer of the oropharynx and hypopharynx.

One hundred patients with stage II and stage III cancer of the oropharynx and hypopharynx were treated under a protocol in which they were randomly selected for treatment by surgery alone or by combined preoperative radiotherapy and surgery. The schedule of preoperative radiation therapy chosen was 2,000 rads from a cobalt 60 machine delivered in five days. Eighty-six of the patients were evaluable at three years; there was no difference in the outcome of the treatment of the two groups. A similar study is urgently needed to determine the value of postoperative radiotherapy in the management of similar cancers.

Adult↗
PubMed1978

Tuftsin (an Ig-associated tetrapeptide) triggers the immunogenic function of macrophages: implications for activation of programmed cells.

The immunoglobulin heavy-chain-associated tetrapeptide, tuftsin (Thr-Lys-Pro-Arg), known for its phagocytosis-stimulating activity, was found to augment the antigen-specific, macrophage-dependent education of T lymphocytes. The investigation of stereospecific characteristics of the tetrapeptide, by use of structural analogs with different modifications, revealed strict structural requirements for eliciting the immunogenic activity of macrophages. It was found that the most important moiety for its activity is the dipeptide Pro-Arg. This finding is of interest in view of the appearance of this particular dipeptide in other bioregulatory peptides, including many of the peptide hormones. The significance of the appearance of a common structure in such molecules, which may act through specific receptors on different target cells, is discussed.

Amino Acid Sequence↗
PubMed1978

Role of gastrin heptadecapeptide in the acid secretory response to amino acids in man.

Amino acids and peptides release gastrin and stimulate gastric acid secretion. However, the relation between gastrin release and acid secretory response is unclear. An isotonic mixed amino acid solution (casein hydrolysate) was continuously infused into the stomach of eight healthy human subjects. Acid secretion, measured by in vivo intragastric titration, increased 12.8 meq/h over the response to intragastric infusion of isotonic saline. Plasma gastrin heptadecapeptide (G-17) concentration, measured by specific radioimmunoassay, increased 13 pmol/liter during intragastric amino acid infusion. To determine whether this rise in plasma G-17 concentration could account for some or all of the acid secretory response, several doses of synthetic human G-17-I were infused intravenously into the same subjects. During i.v. G-17-I infusion, the stomach was continuously infused with isotonic saline. By graphically relating plasma G-17 concentration during i.v. G-17 infusion to concomitant acid secretion, it was determined that a 13-pmol/liter rise in plasma G-17 concentration could increase acid secretion 14.8 meq/h. Therefore, the rise in plasma G-17 concentration during intragastric amino acid infusion could have produced all of the observed acid secretory response. This suggests that gastrin heptadecapeptide is the major physiologic mediator of the human acid secretory response to meals containing mixed amino acids.

Adult↗
PubMed1978

Histamine H2-receptor antagonists.

Development of histamine H2-receptor antagonists has enhanced the understanding of histamine physiology and pharmacology. The effect of H2-receptor antagonists on gastrointestinal physiology has been studied extensively. These compounds inhibit gastric acid secretion in response to all known secretagogues and, in contrast to anticholinergic drugs, markedly inhibit food-stimulated acid secretion in duodenal ulcer patients. The relative roles of H2-receptor antagonists, anticholinergic drugs and antacids in the treatment of duodenal ulcer remain to be defined. Cimetidine currently is under investigation for the treatment of duodenal ulcer, gastric ulcer, reflux esophagitis, gastrointestinal bleeding and hypersecretory states. Although the long-term safety of cimetidine has not been established, in short-term clinical trials there have been no significant subjective or objective side-effects. Assuming that toxic effects do not develop, H2-receptor antagonists should improve the treatment of acid-peptic disease.

Cimetidine↗
PubMed1978

Generation of suppressor lymphocytes during sensitization in culture against a syngeneic tumor: affinity chromatography on insolubilized histamine.

We investigated the effect of depletion of histamine-binding lymphoid cells on immunological properties of lymphocytes sensitized in culture against tumor cells. C57BL/6 spleen cells that were sensitized in vitro on monolayers of the syngeneic Lewis lung carcinoma (3LL) became cytotoxic to the tumor cells in vitro after 3 to 5 days of sensitization. Sensitized cells harvested after 4 days of sensitization occasionally enhanced tumor growth in vivo. Fractionation of the sensitized lymphocytes over insolubilized histamine-rabbit serum albumin-Sepharose (HRS) columns decreased or abolished the enhancing activity in vivo and specifically increased the in vitro cytotoxic activity of the depleted lymphocytes. A similar increase in the cytotoxic activity of HRS-fractionated cells was observed in an allogeneic combination of C57BL spleen cells sensitized against C3H fibroblasts. The effect of HRS chromatography on the in vitro cytotoxic activity increased with prolonged incubation of the depleted effector cells with the target cells.

Animals↗
PubMed1978

Macrophage-mediated in vitro sensitization of lymphocytes. II. The detection of neo-antigens on transformed lymphocytes and passages of normal fibroblasts.

Unprimed lymphocytes were sensitized in vitro by incubating them with syngeneic macrophages that had been fed with viral or cellular antigens. The sensitized lymphocytes were tested for their cytotoxic activity against virus-infected and noninfected fibroblasts. The antigenic preparations used for priming the macrophages were either tumor cell-free extracts or supernatants from virus productive cells. Cell-free extracts from the productive RadLV-induced lymphoma cells or the nonproductive radiation-induced lymphoma cells were immunogenic when presented to lymphocytes by macrophages. In contrast, cell-free extracts from normal thymocytes were much less immunogenic, suggesting that the presence of viral associated antigens (VAA) can selectively be detected on lymphoma cells by this assay. Fibroblastic cell lines but not primary fibroblasts were also susceptible to the cytotoxic lymphocytes induced by RadLV-fed macrophages. Primary fibroblasts became susceptible to the sensitized lymphocytes either after infection with the corresponding virus, or if not infected, after several passages in vitro, suggesting that neo-antigens cross-reacting with viral antigens appear during sub-culturing of fibroblasts in vitro. This system makes it possible to detect VAA either as immunogens when presented to lymphocytes by macrophages, or as targets for cytotoxic lymphocytes.

Animals↗