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Biomedical subjects

B M Jaffe

Publications and source records attributed to B M Jaffe.

At least 127 records · Page 7Linked to original sources
PubMed1983

Endoluminal substance P as a cause of mucosal hyperemia in the feline gut by a nonneural mechanism.

Exogenous substance P (SP) was perfused into the lumen of the proximal jejunum in 16 fasted cats at a rate of 6.04 +/- 1.96 ng/min. Regional blood flow was measured by radioactive microspheres after successive 15-minute perfusions with saline (basal), neural blockers, SP, and saline. Endoluminal SP caused mucosal hyperemia in the perfused jejunal segment that was not blocked by preperfusion of the segment with lidocaine (2% or 4%) or tetrodotoxin (3 X 10(-7) M). In addition, there was no increase in blood flow to any other organ tested, gastrointestinal or systemic. Local luminal SP levels rose but there was no significant rise in portal SP levels, indicating that the peptide was not absorbed. The data suggest that SP acts locally by a nonneural mechanism to influence local gastrointestinal blood flow.

Animals↗
PubMed1983

Release of substance P from the enteric nervous system: direct quantitation and characterization.

A dynamic system has been developed in which in vitro release of substance P (SP) from two longitudinal muscle-myenteric plexus strips from the guinea-pig ileum is obtained during continuous superfusion and measured directly by using a highly sensitive radioimmunoassay specific for SP. Electrical stimulation (0.5-40 Hz) produced a marked increase in the rate of release of SP. The magnitude of the increase in the rate of electrically evoked release was dependent on the frequency of stimulation but this dependence did not appear to be linear over the entire range tested. Electrically evoked release elicited by 20 Hz stimulation was reduced by 95% by omitting Ca++ from the superfusion buffer or by cooling the preparation to 3 degrees C. Pretreatment with tetrodotoxin (1 micrograms/ml for 15 min) substantially reduced the magnitude of the increase in the rate of release of SP but did not abolish it. Despite tetrodotoxin pretreatment, a significant portion (53%) of the electrically induced increase in SP release remained. The ability of electrical stimulation to release SP from the myenteric plexus in amounts sufficient to produce a physiological response in a Ca++- and temperature-dependent fashion in combination with data provided by indirect pharmacological experiments strongly suggests that SP functions as a neurotransmitter in the enteric nervous system.

Animals↗
PubMed1983

Bombesin and insulin-stimulated pancreatic polypeptide release as a discriminator of vagal integrity.

Intact vagi after ulcer operations are often implicated in the cause of recurrent ulcer. The stimulation of gastric acid by insulin hypoglycemia is dangerous and the measurement of acid secretion after gastrectomy unreliable. This study was undertaken to assess and compare PP release by bombesin or insulin as an indicator of vagal integrity. Eight dogs with a chronic gastric fistula were tested with bombesin (100 nanograms per kilogram) and insulin (0.1 unit per kilogram) intravenous bolus after unilateral and, then, bilateral truncal vagotomy. Each study was 120 minutes, and blood was taken at one, three, five, seven and then ten minute intervals. Gastric acid was measured by autobiuret titration. Plasma was stored at minus 20 degrees C. until assayed for PP by radioimmunoassay. Bombesin-stimulated gastric acid secretion was not significantly altered by vagotomy (p greater than 0.05), whereas that stimulated by insulin was significantly inhibited by bilateral truncal vagotomy (p less than 0.05). Bilateral and right hemivagotomy significantly inhibited PP release by bombesin (p less than 0.05), however, only bilateral truncal vagotomy significantly inhibited PP release by insulin (p less than 0.05). These results suggest that the measurement of PP release by insulin or bombesin is a sensitive index of vagal integrity and that bombesin-released PP may specifically delineate the integrity of the right vagus. Since the measurement of gastric acid secretion after operation is both uncomfortable and often difficult to interpret, the value of a simple blood test to determine vagal integrity may be of considerable clinical relevance.

Animals↗
PubMed1983

Prostaglandin generation in the gastric mucosa of rats with stress ulcer.

Prostaglandins, normally synthesized by the gastric mucosa, have been shown to prevent the formation of experimentally induced ulcers, including stress ulcers. A physiologic role of these compounds in the protection of the gastric mucosa has been postulated. In order to assess the role of endogenous prostaglandins in the pathogenesis of stress ulceration, we measured the amounts of prostaglandin E (PGE) generated by gastric mucosal samples from rats exposed to cold restraint stress. Stress induced a significant inhibition of PGE biosynthesis by the gastric mucosa. The inhibition was similar to that caused by indomethacin. The degree of inhibition of PGE generation significantly correlated with the severity of the gastric mucosal lesions (P less than 0.001). Identical effects were identified in antrum and fundus. The decrease of PGE mucosal biosynthesis seems to be a major determinant in the pathogenesis of stress ulceration.

Animals↗
PubMed1983

Evaluation of the student: improving validity of the oral examination.

Medical students completing a surgical clerkship were scored independently by faculty members, a chief resident and a written multiple-choice examination. In group I, an oral examination was administered by two faculty members together in one room, while in group II, the examiners were in separate rooms. The average oral examination grade correlated with none of the other facets of the student evaluation in group I, but did so for most parameters in group II. The correlation coefficient between the oral examination and mean grade became significant, however, for oral examinations in which five or more core topics were covered. It is concluded that even with limited professional resources, changes in the method of administering an oral examination can increase its validity.

Education, Medical↗
PubMed1982

PGE restores the immune response in chemotherapy-treated, tumor-bearing mice.

Two hundred seventy-one B-16 melanoma-bearing mice were randomized and treated for 4 days with either control diluent, 10 micrograms of 16,16-dimethyl-PGE2-methyl-ester (di-M-PGE2), chemotherapy, or chemotherapy plus di-M-PGE2. The chemotherapeutic regimens included adriamycin (7.5 mg/kg), 5-fluorouracil (250 mg/kg), nitrogen mustard (5 mg/kg), and vincristine (0.5 mg/kg). The number of plaque-forming cells and hemagglutinin titers in response to sheep erythrocytes were used as measures of humoral immunity while cellular immunity was assessed by evaluation of delayed hypersensitivity. As we previously reported, the presence of subcutaneous B-16 tumors induced substantial immunosuppression and this suppression was reversed by treatment with di-M-PGE2. Treatment with all four chemotherapeutic agents induced profound immunosuppression. Similarly, the addition of di-M-PGE2 to the chemotherapy protocols resulted in significant augmentation of cellular and humoral immunity.

16,16-Dimethylprostaglandin E2↗
PubMed1982

Cholinergic modulation of substance P release.

This study was initiated to evaluate mechanisms of release of immunoreactive substance P into the peripheral circulation and to determine whether these mechanisms are subject to cholinergic modulation. In conscious dogs, a high-protein meal significantly increased plasma concentrations of immunoreactive substance P from basal levels of 13.7 +/- 1.8 pg/ml to a peak of 20.1 +/- 2.8 pg/ml after which they returned to baseline. Prior atropinization (200 mg/kg) abolished this response and lowered the plasma levels to a nadir of 2.2 pg/ml at 20 min. Similarly, infusion of bombesin (17 ng/kg/min) increased peripheral venous substance P levels by 768 +/- 155 pg-min/ml for 120 min, whereas after prior treatment with atropine, bombesin released no significant amounts of this peptide (-10 +/- 134 pg-min/ml). The data support the concept that substance P release is under cholinergic control.

Animals↗
PubMed1982

Effect of methionine-enkephalin and naloxone on bombesin-stimulated gastric acid secretion, gastrin, and pancreatic polypeptide release in the dog.

In four dogs with chronic gastric fistulae, bombesin infusion was used to stimulate the release of gastrin and pancreatic polypeptide (PP) as well as rates of gastric acid secretion. Neither methionine-enkephalin (met-enkephalin) nor naloxone alone or the combination of these agents altered bombesin-stimulated gastrin release. met-enkephalin alone (but not naloxone) significantly inhibited the gastric secretory response to bombesin, but this inhibitory effect was not influenced by the simultaneous infusion of naloxone; the data suggested that the effect of met-enkephalin was indirect, and perhaps modulated by another inhibitory mechanism. Whereas PP release induced by bombesin was not affected by naloxone, it was significantly suppressed by met-enkaphalin; since this inhibition was virtually totally reversed by naloxone, the data suggested that the effect of opiate peptides on the release of pancreatic polypeptide was direct and mediated by a specific opiate receptor.

Animals↗
PubMed1982

The early diagnosis of gastrinoma.

Despite the increasing awareness of gastrinoma and its lethal peptic ulcer sequelae, the diagnosis is often initially missed or made as a terminal event. The authors screened all patients with peptic ulcer symptoms serious enough to warrant hospital admission or those associated with diarrhea, nephrolithiasis, hypercalcemia, or pituitary abnormality. In a one-year period (1979-1980) nine (of 14 suspected) new gastrinoma patients were identified using a sensitive and specific gastrin radioimmunoassay in combination with provocative tests including IV secretin, calcium, and food. Conventional upper GI series, CAT scan, arteriography, and endoscopy provided no additional information other than to confirm the presence of ulcer disease. Basal plasma gastrin levels were more than 200 pmol L-1 in only three of the nine (normal fasting plasma gastrin levels are less than 25 pmol L-1). Three patients presented with acute ulcer perforation, and the diagnosis of gastrinoma was suspected because of multiple ulcers and pancreatic masses. In three other patients, previous duodenal ulcer surgery had failed. One patient with dyspepsia, high basal plasma gastrin, negative secretin and calcium infusion studies, and a positive meal test was diagnosed as having G-cell hyperplasia; this was confirmed by biopsy and antral gastrin extraction. Antrectomy alone resulted in cure. In all patients tested, a positive calcium infusion or secretin bolus (greater than 100% rise over basal) strongly suggested the diagnosis of gastrinoma, which was confirmed at surgery. In the acute perforations, initial management with omental patch and cimetidine therapy allowed survival of two patients, while emergency total gastrectomy in the third resulted in death due to esophagojejunal leak. Elective patients were treated with cimetidine initially for at least two weeks before total gastrectomy. In this group there were no operative mortalities, and postoperative morbidity was minimal. This series illustrates three important points: (1) careful screening of an ulcer population using gastrin radioimmunoassay and provocative tests has enabled a high yield of gastrinomas while conventional investigations are of minimal values; (2) a high index of suspicion in appropriate cases is necessary; and (3) total gastrectomy performed under elective circumstances is safe and allows the patients to resume a normal and healthy life without the sequelae of aggressive peptic ulceration or daily drug administration.

Adult↗
PubMed1982

Antiviral effect of prostaglandins of the A series: inhibition of vaccinia virus replication in cultured cells.

Prostaglandins of the A series potently inhibited the production of vaccinia virus in mouse L fibroblasts. With the highest non-toxic dose of PGA1, 4 micrograms/ml, the replication of the virus was inhibited by 95 . 3%. The antiviral activity was dose-dependent and specific for the A series. At the dose used, PGA1 was not toxic to uninfected cells and did not alter cell metabolism as measured by DNA, RNA and protein synthesis. PGA1 did not influence the adsorption of the virus by the host cells and the antiviral activity was not dependent on the presence of PGA1 during the early stages of infection. PGA treatment delayed and partially inhibited virus DNA synthesis and, while it did not produce any change in the pattern of protein synthesis in uninfected cells, it altered both the rate and the pattern of virus protein synthesis. We conclude that PGA1 selectively inhibits one or more steps involved in the replication of vaccinia virus in mouse L fibroblasts.

Adsorption↗
PubMed1982

Effect of xenopsin on blood flow, hormone release, and acid secretion.

We investigated the effects of the neurotensin analogue xenopsin on regional blood flow, central hemodynamics, and stimulated acid secretion in awake conscious dogs. Organ blood flow, estimated using the radioactive microsphere technique, was significantly increased during the xenopsin infusion to the adrenals, pancreas, and ileum. There was no change in mean arterial pressure or cardiac output (measured by thermodilution). Along with changes in blood flow, there was a significant increase in the hormone output from the pancreas. These included rises in plasma pancreatic polypeptide, insulin, and glucagon. There also was a rise in plasma cortisol levels during the infusion. Substance P levels rose slowly but significantly during the xenospin infusion. There was no change in plasma gastrin levels. Xenopsin produced a significant inhibition of tetragastrin-stimulated gastric acid output. Thus, xenopsin appears to have region-specific influence on blood flow that correlates with region-specific hormonal secretion. In addition, xenopsin, like its mammalian analogue neurotensin, is an inhibitor of stimulated gastric acid secretion. A mammalian xenopsinlike peptide may well be involved in the modulation of gastrointestinal function.

Adrenal Glands↗
PubMed1982

Postnatal development of intestinal secretin in rats and guinea pigs.

The amounts and concentrations of secretin in extracts of rat and guinea pig small intestine were measured with a porcine secretin radioimmunoassay. Immunoactivity in the extracts comigrated with porcine secretin in sodium dodecyl sulfate acrylamide gel electrophoresis. In the small intestines of adult rats and newborn and adult guinea pigs, there was a marked proximal-to-distal gradient in secretin concentration; newborn rats exhibited approximately equal proximal and distal secretin concentrations. Concentrations were as follows: most proximal newborn or adult guinea pig segments, 80 ng/mg prot; most distal newborn or adult guinea pig segments, 2 ng/mg prot; most proximal adult rat segments, 50 ng/mg prot; most distal adult rat segments, 8 ng/mg prot; and newborn rat intestine, 11 ng/mg prot. In either rats or guinea pigs, the secretin concentration in the proximal small intestine fell between days 2 and 6 postpartum to levels 3- and 10-fold below their respective newborn values. It is consistent with the relatively mature state of the newborn guinea pig digestive tract that it displays the proximal-to-distal gradient of secretin that is characteristic of both adult guinea pigs and rats. In the proximal intestine of both species, intestinal growth outpaces the accumulation of secretin.

Aging↗