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Biomedical subjects

B M Jaffe

Publications and source records attributed to B M Jaffe.

At least 145 records · Page 8Linked to original sources
PubMed1982

Local regulation of blood flow in the feline jejunum. A possible role for endoluminally released substance P.

Serotonin and substance P of gastrointestinal origin have been measured by radioimmunoassay in the bowel lumen under basal and stimulated conditions. To investigate the possibility that local blood flow may be influenced by these endoluminal hormones, 26 cats were studied with exogenous serotonin and substance P infused endoluminally into isolated proximal jejunal segments in vivo. Regional blood flow was measured by using the radioactive microsphere technique before, during, and after the endoluminal instillation of two doses of substance P (3.9 and 30 ng/min) or serotonin (0.9 and 21 micrograms/min). Neither dose of substance P changed systemic blood pressure. Substance P at the low dose caused an increase in blood flow to the experimental jejunal mucosa (from 53 +/- 10 ml/min per 100 g to 102 +/- 20 ml/min per 100 g, P less than 0.01). The higher dose of endoluminal substance P similarly increased blood flow to the experimental jejunal mucosal fraction, and also increased blood flow to the experimental jejunal muscularis fraction (from 17 +/- 3 ml/min per 100 g to 23 +/- 3 ml/min per 100 g, P less than 0.02). Serotonin increased blood flow to the experimental jejunal muscularis only at the high dose (17 +/- 4 ml/min per 100 g to 25 +/- 4 ml/min per 100 g tissue, P less than 0.01). These results provide evidence for a dose-related local effect of endoluminal substance P on gastrointestinal blood flow.

Animals↗
PubMed1982

Effect of cervical and thoracic vagal stimulation on luminal serotonin release and regional blood flow in cats.

In acute experiments on 14 cats, the transected vagus nerves were stimulated at two levels (10 V, 5 ms, 10 Hz, 10 mA, 15 min). Fifteen-centimeter proximal jejunal segments were perfused with saline (1.0 ml/min). Basal luminal immunoreactive serotonin secretion averaged 206 +/- 67 ng/5 min. After stimulation of the vagus nerves, there was an immediate two- to threefold increase in the rate of secretion of immunoreactive serotonin into the lumen. There were no significant differences in the stimulated secretory rates that resulted from stimulation at the cervical or thoracic levels. Shortly after cessation of vagal stimulation, immunoreactive serotonin secretory rates returned to basal. Vagal nerve stimulation did not result in any change in peripheral or portal venous blood concentrations of serotonin. In 12 additional cats, the effects of stimulation of the vagus nerves at the cervical and thoracic levels on regional blood flow, as determined using the microsphere technique, were compared. Cervical vagal stimulation resulted in hypotension, bradycardia, decreased perfusion of the heart, kidney, and small and large bowels, but preservation of the perfusion of the fundus and antrum. In contrast, stimulation of the transected nerves in the chest stimulated gastric blood flow but did not alter either flow to other viscera or central hemodynamics.

Animals↗
PubMed1982

Opiate modulation of pancreatic polypeptide release by a meal in the dog.

It has been reported that morphine abolished the plasma pancreatic polypeptide (PP) response to a meal in man, but the mechanism of this action is unclear. This study was designed to investigate the effect of low doses of the endogenous opiate peptide. Met-enkephalin and naloxone on basal- and meal-stimulated PP release in order to examine the role of opioid modulation in the release of this hormone. Four gastric fistula dogs underwent a series of six studies, a test meal alone. Met-enkephalin infusion (40 microgram/kg/hr), naloxone infusion, meal plus naloxone infusion and meal plus Met-enkephalin plus naloxone. Gastrin and PP were measured by radioimmunoassay. Basal PP levels averaged 35.1 +/- 3.0 fmol/ml. Although Met-enkephalin had no effect on basal PP levels, it significantly (P less than 0.05) inhibited the mean peak increment of PP stimulated by a meal (control, 331 +/- 39 fmol/ml; Met-enkephalin, 145 +/- 49 fmol/ml; P less than 0.05). This inhibition was completely abolished by naloxone. Naloxone alone did not alter basal- or meal-stimulated plasma PP levels. Neither Met-enkephalin nor naloxone altered basal or stimulated plasma gastrin levels. This study demonstrated that opiate peptides play a role in the regulation of the release of PP by a meal; it thus suggests the possibility of an opioid modulatory mechanism for the release of this hormone.

Animals↗
PubMed1981

Release of immunoreactive serotonin into the lumen of the feline gut in response to vagal nerve stimulation.

Immunoreactive serotonin was detected in the lumen of the proximal jejunum of food-deprived cats. During perfusion of this intestinal segment in vivo, there was a constant basal rate of intraluminal secretion of this amine. The rate of secretion was significantly increased during efferent electrical stimulation of the cut cervical vagal nerves. This stimulatory effect was not altered after bilateral adrenalectomy was performed in the same animals. A synchronous release of substance P into the gut lumen was also demonstrated during vagal stimulation. During the period of increased intraluminal secretion of immunoreactive serotonin, there was no demonstrable change in the portal or systemic blood levels of this amine.

Adrenalectomy↗
PubMed1981

Evidence for an intestinal mechanism of pancreatic polypeptide release.

The purpose of this study was to define the existence of an intestinal phase of pancreatic polypeptide (PP) release and to assess whether it was mediated by a cholinergic-sensitive mechanism. Four conscious dogs with 20-cm upper intestinal Thiry-Vella loops and chronic gastric fistulas were used. The Thiry-Vella (T-V) loops were perfused with 10% liver extract or 0.154 M NaCl at a rate of 1 ml/min for 120 min. In a separate experiment, 240 ml of 10% liver extract was infused over a 5-min period into the stomach via the gastric fistula. Basal PP levels were 29 +/- 4 fmol/ml. The gastric infusion of liver extract caused a significant increase of plasma PP levels to a peak of 215 +/- 29 fmol/ml (P less than 0.05). The perfusion of the T-V loop with liver extract significantly increased plasma PP levels over basal to a peak of 73 +/- 14 fmol/ml (P less than 0.05). This value was significantly less than that released by gastric infusion of liver extract (P less than 0.05). Perfusion of the loop with NaCl did not significantly alter basal plasma PP levels (P greater than 0.05). PP release by perfusion of the T-V loop with liver extract was abolished by atropine intravenous bolus (0.2 mg/kg). Although the combination of bethanechol (100 microgram/kg/hr intravenous) and liver extract consistently increased the plasma levels of PP, the values did not attain statistical significance when compared to liver extract alone (P greater than 0.05). The data presented are thus consistent with the hypothesis that there is an enteric phase of pancreatic polypeptide release and that this enteropancreatic reflex is mediated by a cholinergic-sensitive mechanism which might be hormonal or neural.

Animals↗
PubMed1981

Bombesin: a vagally independent stimulator of gastrin release.

In this study we demonstrate that bombesin is a potent stimulant of canine gastrin and gastric acid secretion. Bombesin was shown to release almost fourfold more gastrin than a meal by a mechanism which is independent of vagal integrity. An exogenously administered cholinomimetic agent released only minimal amounts of gastrin after vagotomy and virtually none in the intact canine model. The combination of bombesin and bethanechol caused a significant increase in acid secretion compared with bombesin alone and was associated with a marked inhibition of gastrin release both before and after vagotomy. Gastric acid secretion in response to bombesin was not significantly altered by vagotomy. We interpret these data to reflect the sensitivity of bombesin-stimulated gastrin release to gastric luminal pH, although they also suggest the existence of a cholinergic inhibitory mechanism for gastrin release. The data provided by this study are consistent with the hypothesis that bombesin might function as a paracrine neuromodulator of gastrin release. in view of its presence in the nerves and mucosa of human stomach and its potent actions on gastrin release and gastric acid secretion, bombesin may play a role in gastric physiology.

Animals↗
PubMed1981

The effect of somatostatin and 16,16-dimethyl-prostaglandin E2 on bombesin-stimulated canine gastric acid, plasma gastrin and pancreatic polypeptide secretion.

We studied the effect of the intravenous infusion of 16,16-dimethylprostaglandin E2 methyl ester (di-M-PGE2) and somatostatin on bombesin-stimulated gastric acid secretion, plasma gastrin and plasma pancreatic polypeptide in four chronic gastric fistula dogs. Bombesin-stimulated gastric acid secretion was significantly inhibited by somatostatin and virtually abolished by di-M-PGE2. Both agents caused significant, but indistinguishable inhibition of gastrin release (P less than 0.05). Bombesin-stimulated pancreatic polypeptide release was also significantly inhibited by both somatostatin and di-M-PGE2; the inhibitory effect of somatostatin was significantly greater than that of di-M-PGE2 (P less than 0.05). This study provides further evidence in support of the complex interrelationships between agents responsible for the modulation of gastrointestinal physiology.

16,16-Dimethylprostaglandin E2↗
PubMed1981

Prostaglandins of the A series inhibit Sendai virus replication in cultured cells.

Prostaglandins of the A series (PGA) were shown to be potent inhibitors of Sendai virus replication in African green monkey kidney cells in culture. This antiviral activity was specific for PGA. The effective dose (4 micrograms/ml) was not toxic to the cells and did not alter either host cell metabolism of infectivity of the virus. PGA did not affect the first stages of virus replication and seemed to act by inhibiting virus maturation and/or budding from the cells. The antiviral action of PGA was pharmacological, was not mediated by cAMP and was completely reversible. Possible mechanisms of action include post-translational binding to virus proteins or interaction with interferon.

Animals↗
PubMed1981

Stimulated gastric prostaglandin output, and the effect of inhibition of prostaglandin synthetase, in the conscious cat.

1. In the conscious gastric fistula cat there was no correlation between the outputs of gastric acid and PGE secreted in response to incremental doses of pentagastrin and histamine acid phosphate. 2. PGE secreted in response to pentagastrin and histamine was not dose dependent. 3. Flurbiprofen significantly inhibited the gastric output of PGE but did not influence acid or pepsin secretion. Inhibition of PGE secretion was accompanied by evidence of gastric mucosal haemorrhage. 4. It is concluded that gastric juice PGE is unlikely to be involved in the physiological control of acid secretion.

Animals↗
PubMed1981

Acromegaly and Cushing's syndrome associated with a foregut carcinoid tumor.

We report an 18-yr-old youth with a metastatic foregut carcinoid tumor, Cushing's syndrome, and hypersomatotropic gigantism. Administration of cyproheptadine caused a dramatic fall in urinary cortisol excretion and plasma ACTH levels associated with clinical remission of the Cushing's syndrome. GH secretion was not affected by cyproheptadine administration. Ectopic ACTH secretion was confirmed by RIA of tumor extracts and immunohistochemical demonstration of ACTH-containing cells in hepatic metastases. There were two sources of GH production demonstrated in this patient. Ectopic secretion of GH by the carcinoid hepatic metastases was documented by both RIA and immunohistochemical techniques. A somatotrophic pituitary tumor was also present. The histological characteristics of this tumor suggest adenomatous hyperplasia rather than de novo neoplastic change as the likely mechanism of its pathogenesis. GH releasing factor-like activity was demonstrated in extracts of plasma and in extracts of the carcinoid tumor. We conclude that cyproheptadine exerted an effect on the ectopic ACTH-producing cells but not on the ectopic GH-producing cells or on adenohypophyseal GH secretion. Production of a GH releasing factor-like activity by the carcinoid tumor may have caused the pituitary somatotrophic tumor.

Abdominal Neoplasms↗
PubMed1981

Radioimmunoassay measurement of substance P release following a meat meal.

We report the development of a sensitive and specific radioimmunoassay for substance P based on a new extraction technique for this peptide. In this technique, substance P-like immunoreactivity (SPLI) was extracted from midly acidified plasma successively with 0.05M ammonium sulfate and ethanol; recovery was almost quantitative (89.5 +/- 3.2%) and was independent of concentration. Basal substance P levels averaged 22 +/- 3 pg/ml in 33 dogs. Following initiation of a high-protein meal, mean SPLI levels in three dogs (in a total of 12 experiments) increased significantly from 26 +/- 3 to a peak of 37 +/- 4 pg/ml at 15 minutes, after which they slowly returned to the initial levels.

Animals↗
PubMed1980

Prostaglandin A compounds as antiviral agents.

Prostaglandins of the A series strongly inhibit the production of Sendai virus in African green monkey kidney cells and are able to prevent the establishment of persistent infection ("carrier" state). This action is specific for prostaglandin A and is not due to alteration in the host cell metabolism or in the virus infectivity. The possibility that this effect is mediated by interferon is discussed.

Animals↗
PubMed1980

Value of preoperative evaluation in patients with lymphoma.

The records of 136 patients with Hodgkin's lymphoma and of 32 patients with non-Hodgkin's lymphoma who underwent staging laparotomy were reviewed. There were changes in the clinical stage of 25% of the patients after laparotomy. Forty-one percent of the lymphangiograms and 55% of the liver-spleen scintiscans were inaccurate or nondiagnostic. There were few stage alterations by laparotomy in patients in clinical stages I and II. There was a higher frequency of stage changes in clinical stage III1 and III2 patients. Staging laparotomy is not recommended for clinical stages I and II but is mandatory for stages III1 and III2.

Adolescent↗
PubMed1980

The interactions between indomethacin and cytotoxic drugs in mice bearing B-16 melanomas.

We have compared the effects of indomethacin alone (100 microgram/mouse/day) with those of indomethacin plus adriamycin, 5-FU, nitrogen mustard, thioTEPA, and vincristine on B-16 tumor cell proliferation in vivo. As we have previously described, after four days of treatment with indomethacin, subcutaneous tumors were slightly smaller and lighter in weight, but contained more melanoma cells. Addition of indomethacin to cytotoxic regimens resulted in either no change or a decrease in the effectiveness of the chemotherapy. In previous studies we demonstrated that treatment of tumor-bearing mice with a long-acting synthetic analogue of PGE2 (di-M-PGE2) stimulated the synthesis of endogenous prostaglandins. In order to evaluate if these endogenously synthesized prostaglandins were responsible for the inhibition of B-16 growth in vivo, mice were treated with di-M-PGE2 or di-M-PGE2 plus indomethacin. Addition of indomethacin did not alter the tumor inhibitory effects of di-M-PGE2.

16,16-Dimethylprostaglandin E2↗
PubMed1980

The effect of PGA1 on the immune response in B-16 melanoma-bearing mice.

This study evaluated the effects of PGA1 on B-16 melanoma-bearing mice. Intraperitoneal injection of PGA1 (10 microgram/day) significantly inhibited the rate of melanoma growth measured both as delay in the rate of appearance and decrease in the tumor volume. In contrast to the diluent control-treated mice, by 17 days, less than half of the PGA1-treated animals developed measurable (greater than 2 mm) subcutaneous tumors. In addition to its effect on tumor size, PGA1 was also effective in stimulating both the humoral and cellular components of the immune response. B-16 tumor-bearing mice were shown to be immunosuppressed, in that they had decreased anti-sRBC hemagglutinin titers, decreased splenic plaque-forming cells, suppressed delayed hypersensitivity responses, and delayed rejection of skin allografts from BALB/c mice. Although, PGA1 had relatively little effect on normal mice, this prostaglandin substantially improved all these immunologic parameters in tumor-bearing animals.

Animals↗