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Biomedical subjects

B M Jaffe

Publications and source records attributed to B M Jaffe.

At least 163 records · Page 9Linked to original sources
PubMed1980

Influence of PGE on the immune response in melanoma-bearing mice.

This study was performed to correlate the role of exogenous and endogenous prostaglandins on humoral and cellular immune responses to and rate of growth of B-16 melanoma in vivo. B-16 melanomas synthesized 7 times as much PGE as did adjacent normal tissues, an effect that was abolished by indomethacin. In C57BL/6J mice bearing B-16 melanomas splenic plaque-forming cells, hemagglutinin titers, and delayed hypersensitivity (all to SRBC) were profoundly suppressed; these responses were significantly augmented by treating the mice with di-M-PGE2 (16, 16-dimethyl-PGE2-methyl ester), a long acting analogue of PGE2, and either further suppressed or unaffected by indomethacin, a potent inhibitor of endogenous PGE biosynthesis. Compared to control experiments, indomethacin hastened the rate of development of palpable subcutaneous B-16 tumors and facilitated the proliferation of these cells in solid tumors as well as in ascites. Pretreatment of mice with di-M-PGE2 (before inoculation with tumor cells) resulted in delay in the rate of appearance of tumors, decline in the growth rate, and increased survival. These data suggest that prostaglandins are involved in the control of in vivo tumor cell growth largely by virtue of their effects on the immune response.

Agglutinins↗
PubMed1979

Prostaglandins and serotonin: nonpeptide diarrheogenic hormones.

Prostaglandins and serotonin are vasoactive compounds with profound effects on the gastrointestinal tract. Both cause inhibition of gastric acid secretion (although serotonin stimulates gastric pepsin secretion), stimulation of intestinal motility, and conversion of small intestinal mucosa from absorption to secretion of water and electrolytes. Their effects on pancreatic and biliary function are still not clear. Although prostaglandins appear to elicit their effects primarily by a paracrine mode of action, and serotonin is primarily a neurotransmitter (neurocrine), it is clear that even under normal conditions both can function as humoral agents. For example, we have shown that serotonin plays a physiologic role as a humoral inhibitor of gastric acid secretion. However, the effects of these agents become more pronounced in patients with humorally mediated diarrheogenic syndromes. Serotonin (and related indoles, particularly 5-hydroxytryptophan) has been firmly implicated as a cause of diarrhea in patients with carcinoid syndrome; our recent studies suggest that the diagnosis can be more effectively made by measuring circulating immunoreactive serotonin concentrations than urinary excretion of 5-HIAA; that some circulating serotonin escapes hepatic inactivation and, thus, large intestinal tumors can cause carcinoid syndrome in the absence of hepatic metastases; and that large amounts of serotonin are produced by some noncarcinoid diarrheogenic tumors, including medullary carcinomas of the thyroid and tumors associated with the WDHA syndrome. A large number of tumors of probable neural crest origin, including medullary thyroid carcinoma, carcinoids, and tumors associated with the WDHA syndrome, secrete large amounts of prostaglandins, particularly PGE2. The clinical response of at least some of the patients harboring these tumors to inhibitors of prostaglandin synthesis (particularly indomethacin) suggests that prostaglandins play a role in the etiology of these diarrheogenic syndromes.

Animals↗
PubMed1979

Immunocytochemical demonstration of 5-hydroxytryptamine in gastrointestinal endocrine cells.

We have been able to demonstrate 5-hydroxytryptamine in the enterochromaffin cells of the mammalian gastrointestinal tract, using a highly specific antiserum. Conventional histochemical techniques for identifying amines as cell markers can thus be replaced by more reliable and sensitive immunocytochemical methods. This has been facilitated by the use of p-benzoquinone as fixative which has been shown to preserve the localization and antigenicity of amines, as well as peptides.

Animals↗
PubMed1979

Prostaglandin A1 induces differentiation in Friend erythroleukemia cells.

The effect of different prostaglandins and prostaglandin-metabolites on the growth and differentiation of Friend erythroleukemia cells (FLC) was evaluated. The prostaglandin-metabolites, thromboxane B2 and 6-keto PGF1 alpha, were completely inactive, while PGE1 inhibited slightly and PGF2 alpha stimulated the replication of FLC. PGA1 was found to be the most active compound. It profoundly inhibited the replication of both DMSO-treated and undifferentiated FLC. Most importantly, PGA1 alone induced differentiation in FLC, stimulating hemoglobin production over a five-day period. PGA1-stimulated differentiation was completely suppressed by the addition of 10(-6)M hydrocortisone. Finally, treatment of DMSO-differentiated cells with PGA1 (but no DMSO) prevented the return to the undifferentiated state.

Animals↗
PubMed1979

Effect of endogenous and exogenous prostaglandin E on Friend erythroleukaemia cell growth and differentiation.

The effect of exogenous and endogenous prostaglandins on the patterns of growth and differentiation of Friend erythroleukaemia cells (FLC) were studied. During the differentiation process, DMSO stimulated PGE synthesis by an average of 95%. The addition of a long-acting synthetic analogue of PGE2,16,16-dimethyl-PGE2-methyl ester (di-M-PGE2) to the culture medium only slightly and temporarily slowed cell growth, with no appreciable induction of differentiation. However, in the presence of DMSO, the same concentration of di-M-PGE2 produced 73% inhibition of cell growth and accelerated and potently stimulated haemoglobin production. The action of both di-M-PGE2 and DMSO on cell proliferation was dependent upon the state of cell growth at the time of the administration of these compounds. FLC cultures treated with DMSO + di-M-PGE2 produced considerable amounts of haemoglobin before even one duplication cycle was completed. Both DMSO and di-M-PGE2 stimulated endogenous PGE biosynthesis, and the biosynthetic effect of these compounds was synergistic. Inhibition of endogenous prostaglandin synthesis by indomethacin completely abolished the effects produced by DMSO + di-M-PGE2 on the growth, and substantially reduced the stimulated differentiation of FLC. These data suggest that an endogenously synthesized prostaglandin plays a significant role in both the inhibition of replication and in the stimulation of differentiation induced by DMSO and di-M-PGE2 in Friend erythroleukaemia cells.

Cell Differentiation↗
PubMed1979

Inhibition of Friend erythroleukaemia-cell tumours in vivo by a synthetic analogue of prostaglandin E2.

The effect of 16,16-dimethyl-PGE2-methyl ester (di-M-PGE2), a long-acting synthetic analogue of prostaglandin E2, on the replication of Friend erythroleukaemia cells (FLC) in vivo has been studied. Pre-treatment in vitro of both undifferentiated and differentiated FLC with di-M-PGE2 (1 microgram/ml) did not alter rates of tumour appearance or growth, but increased the median survival of DBA/2J mice. Systemic administration of di-M-PGE2 (10 microgram/mouse/day) was not toxic to the mice, but significantly inhibited tumour growth and increased median survival in mice injected s.c. with undifferentiated FLC. These effects of di-M-PGE2 were much more pronounced in mice receiving differentiated (DMSO-treated) FLC. In this latter group, the appearance of tumour was also significantly delayed by di-M-PGE2. The different effects of di-M-PGE2 treatment on tumours derived from undifferentiated and differentiated cells suggest that the analogue is acting directly on tumour-cell replication rather than on factors related to the host response.

Animals↗
PubMed1979

Endogenous prostaglandins and stimulated gastric secretion in the cat: the effect of various secretory inhibitors.

1. The effects of cimetidine, somatostatin and atropine upon the outputs of acid, pepsin, prostaglandins (PG) E and F in gastric juice secreted in response to i.v. infusions of pentagastrin and histamine (H) have been studied in the conscious gastric fistula cat. 2. At constant rate infusions secretion of PGE occurs and follows a similar pattern to that of gastric acid. However the ratio of H:PGE varies considerably and to an extent inexplicable in terms of assay variation. 3. Inhibition of acid output is matched by inhibition of the output of PGE, but changes in concentration of PGE suggest this is a volume related phenomenon. 4. It is concluded that gastric juice PGE is most unlikely to have a regulatory effect upon acid secretion.

Animals↗
PubMed1979

Endogenous prostaglandins in peptic ulcer disease.

Plasma concentrations of prostaglandins E and F have been measured by radioimmunoassay in patients undergoing diagnostic upper intestinal endoscopy. The results fail to support a previously reported deficiency of plasma PGE in duodenal ulcer patients. Plasma prostaglandin concentrations failed to correlate with the parameters of gastric secretion studied; and were unaffected by histamine H2-receptor blockade or the activity of duodenal ulceration. During combined pentagastrin and insulin secretory studies there was a significant correlation between the outputs of PGE and acid into gastric juice.

Adolescent↗
PubMed1979

Role of pancreatic polypeptide in canine gastric acid secretion.

The interrelationships of canine pancreatic polypeptide (cPP) and gastric acid secretion were studied in dogs following infusion of histamine or pentagastrin. Pentagastrin stimulated gastric acid release 30-fold and simultaneously increased plasma cPP secretion by an average of 120 pg/ml. Although histamine stimulated gastric acid secretion to a comparable degree, it had no effect on plasma cPP levels. Three mechanisms of inhibition of acid secretion (cimetidine, duodenal acidification, and somatostatin) had different effects on pancreatic polypeptide (PP) levels. With a background infusion of pentagastrin, cimetidine did not affect cPP levels. In contrast, somatostatin dramatically inhibited both gastric fistula output and cPP release. Finally, a 10-min duodenal irrigation with 0.1 N HCl resulted in a brief spike in cPP levels (from 266 +/- 12 to 347 +/- 31 pg/ml) at the time of greatest inhibition of histamine-stimulated acid secretion. Infusions of histamine + porcine pancreatic polypeptide (pPP) at concentrations of 1.0 and 2.25 microgram/kg per h and of pentagastrin + pPP at 2.25 microgram/kg per h closely simulated postprandial cPP levels (mean 1306 +/- 18 pg/ml at 30 min) but produced no change in gastric fistula output. These studies demonstrated that PP levels and rates of gastric acid secretion are unrelated and that at physiologic concentrations PP plays no significant role in the regulation of gastric acid secretion.

Animals↗