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Biomedical subjects

B M Jaffe

Publications and source records attributed to B M Jaffe.

At least 109 records · Page 6Linked to original sources
PubMed1985

The effect of somatostatin on central hemodynamics, renal blood flow, and renal function in dogs.

We investigated the effects of infusion of somatostatin (200 and 500 ng/kg/min) on central hemodynamics and renal blood flow measured with radioactive microspheres. At the lower dose infusion rate somatostatin did not alter any hemodynamic parameter, but at 500 ng/kg/min somatostatin caused minor transient bradycardia, lowered cardiac output, and increased peripheral resistance. Both infusions inhibited renal arterial flow, with decreases noted in both cortical and medullary components. The 20% fall in renal perfusion was confirmed by the hippurate clearance technique, and there was a corresponding 17% decrease in the glomerular filtration rate. In contrast, no changes were noted in urine output, urinary concentrations of sodium or potassium, or urine osmolarity. These hemodynamic and renal side effects might limit the therapeutic usefulness of somatostatin infusion.

Animals↗
PubMed1984

Prostaglandins in commercial milk preparations. Their effect in the prevention of stress-induced gastric ulcer.

To determine if prostaglandins might be the gastroduodenal mucosal protective components in milk, concentrations of prostaglandin E2 (PGE2), thromboxane B2, and 6-keto-PGF1 alpha (the major metabolite of prostacyclin) were measured in aliquots of commercial milk. Whole milk, heavy cream, and yogurt each contained more than 3 ng/mL of PGE2, whereas low-fat milk (2.04 +/- 0.18 ng/mL) and milk from three nursing mothers (0.66 +/- 0.05 ng/mL) contained substantially less. Levels of thromboxane and prostacyclin were much lower, in general, less than 500 pg/mL. In a cold-restraint stress ulcer model in rats, milk was able to inhibit the development of gastric ulcers (50% and ulcer index 5.0 +/- 2.1 v control, 90% and 18.9 +/- 3.8, respectively). Charcoal treatment, which depleted more than 95% of the prostaglandins, rendered the milk nonprotective (80% and ulcer index 15.0 +/- 1.4). These observations are consistent with the concept that prostaglandins may be responsible for the presumed beneficial effects of milk in the prevention and treatment of peptic ulcer disease.

Animals↗
PubMed1984

Substance P in the localization of a carcinoid tumor.

A 55-year-old woman with an ovarian carcinoid presented with intermittent facial and cervical flushing for 10 years, watery diarrhea for 4 years, and abdominal pain without hepatomegaly. Markedly elevated systemic venous and arterial serotonin levels (830 ng/ml; nl = 50-200 ng/ml) were found. The highest serotonin levels were observed in the superior vena caval system, but serotonin as a marker for tumor localization was inaccurate and led to an unproductive neck exploration. The histological pattern of this tumor contained purely insular elements. No hepatic or nodal metastases were identified and the lesion was unilateral. Substance P levels were elevated in the venous drainage of the left ovary and in retrospect correctly localized the ovarian tumor. This peptide may prove to be another carcinoid tumor marker in addition to serotonin and 5-hydroxyindoleacetic acid. Substance P may also be an important mediator of symptoms in patients with carcinoid syndrome.

Carcinoid Tumor↗
PubMed1984

Re-operation for intra-abdominal sepsis. Indications and results in modern critical care setting.

In a 2-year period (1981-1983), 87 abdominal re-explorations (1.6% of total laparotomies) were performed on 77 patients for sepsis in five Downstate hospitals. Fifty-one patients were re-explored solely on clinical grounds, 21 on clinical plus radiographic criteria, four solely on radiographic grounds, and 11 for multiple organ failure. The overall mortality rate was 43%. As expected, the most common laparotomy finding was intra-abdominal abscess (47); other findings included anastomotic leak (14), necrotic bowel (10), evidence of technical error (five), and acalculous cholecystitis (two). The most common clinical findings were localized tenderness, fever, and absent bowel sounds (85%). Fifty-four special studies were performed with an overall accuracy rate of 76%. CAT scans and contrast radiographs were most accurate (92% and 81%) while sonography and gallium scans were less useful (59% and 60%). Seven patients had negative laparotomies. While all were distended and six were febrile, only one patient had focal tenderness. In the 11 patients explored solely for multiple organ failure, six patients had drainable pus despite negative radiographic studies, and two survived. The other five patients had negative laparotomies, and all died. Factors correlated with mortality were age over 50, peritonitis at the primary operation, and multiple organ failure. The approach to these seriously ill patients should be governed by a high index of suspicion. Clinical findings are at least as reliable as sophisticated radiographic modalities of which CAT scan appears to be the most accurate. Re-exploration for multiple organ failure alone will yield a significant group of patients with drainable septic foci and some survivors; thus, exploration for this indication appears to be defensible.

Abdomen↗
PubMed1984

The effect of carcinoid levels of serotonin and substance P on hemodynamics.

Serotonin and substance P circulate in high concentrations in patients with the carcinoid syndrome. These studies were performed to evaluate the effects of intravenous infusions of serotonin and substance P to reproduce carcinoid levels of these agents on central hemodynamics, regional blood flow (using the radioactive microsphere technique), and endogenous hormone release. Serotonin did not affect mean arterial pressure but it significantly increased cardiac output, decreased systematic vascular resistance, and redistributed regional blood flow, increasing blood flow to the heart, adrenals, fundus, and antrum. Substance P significantly decreased mean arterial pressure and systemic vascular resistance, increased cardiac output, and increased blood flow to adrenal, fundus, antrum, liver, and all muscular layers of the stomach and small bowel. Neither serotonin nor substance P affected skin blood flow, nor altered circulating levels of glucose, insulin, or gastrin. Although both of these agents seem to participate in the pathogenesis of the carcinoid syndrome, our studies suggest that it is not possible to ascribe all the hemodynamic abnormalities to either.

Animals↗
PubMed1984

Selective inhibition of viral gene expression as the mechanism of the antiviral action of PGA1 in vaccinia virus-infected cells.

We have previously shown that prostaglandins of the A series are potent inhibitors of the replication of several animal viruses in cultured cells. In this report we have studied the mechanism of the antiviral action of PGA1 in vaccinia virus-infected mouse L cells, where there is an alteration in both the rate and extent of the synthesis of some virus proteins. When cytoplasmic RNAs from PGA-treated, vaccinia virus-infected cells were translated in cell-free systems, similar selective inhibition of the synthesis of some viral polypeptides was observed. The lack of translation of some viral RNAs was not due to an impairment of the methylation process nor to a difference in ionic requirements. PGA1, even at doses as high as 10 micrograms/ml, did not exert any direct inhibitory action on transcription in vitro as measured in two cell-free systems, and had no effect on primary transcription-translation of vaccinia virus RNAs when assayed in coupled cell-free systems. Southern blot hybridization analysis of cytoplasmic RNAs to EcoRI restriction fragments of vaccinia DNA showed that PGA1 was able to induce major changes in the pattern of RNA transcripts during the course of viral infection. We propose that changes in the transcription programme of vaccinia virus RNAs could be due either to an alteration of specific viral proteins that regulate transcription by direct binding of PGA1, or to the synthesis and/or activation of a host product that mediates the antiviral action.

Animals↗
PubMed1984

The effects of intravenous substance P infusion on hemodynamics and regional blood flow in conscious dogs.

substance P concentrations in plasma increase in response to a meal. The effects of intravenous substance P infusions were investigated in seven conscious dogs with doses of peptide (7 ng/kg/min) designed to reproduce the normal postprandial circulating increase in substance P. Substance P levels measured by radioimmunoassay increased 8.6 +/- 4.8 pg/ml in arterial plasma (P less than 0.05) and 3.0 +/- 1.5 pg/ml in mixed venous plasma (P less than 0.05). By use of decay equations, the calculated half-life of exogenous immunoreactive substance P was less than 30 seconds, and this corresponded to rapid abolition of the biologic effects of the peptide upon cessation of the infusion. The integration of the arterial and mixed venous concentration curves allowed calculation of the peripheral inactivation of exogenous immunoreactive substance P as 65.6%. During substance P infusion, mean arterial pressure fell 20 +/- 6 mm Hg at 5 minutes from 124 +/- 6 mm Hg (P less than 0.02). Total systemic vascular resistance was 3102 +/- 196 dynes/sec/cm5 basally, and it fell by 667 +/- 137 dynes/sec/cm5 (P less than 0.05) at 10 minutes. Plasma glucose, insulin, and cortisol concentrations did not change significantly from 83 +/- 4 mg/dl, 5.1 +/- 1.0 microU/ml, and 4.6 +/- 0.5 micrograms/dl, respectively. Radioactive 15 micron microspheres injected at times 0, 20, and 50 minutes into the infusion allowed for identification of statistically significant (P less than 0.05) increases in blood flow to the adrenal gland and the muscular layers of the fundus and the ileum. Thus the infusion of substance P to reproduce postprandial circulating levels of this peptide was followed by an orderly sequence of hemodynamic alterations in the conscious dog. Regional blood flow changes were seen in the muscular layers of the fundus and ileum, which are regions of high substance P concentration.

Animals↗
PubMed1984

The role of substance P in the control of gastric acid secretion.

Experiments were performed to determine whether substance P plays a physiologic role as an enterogastrone. Basal substance P levels averaged 6.4 +/- 0.2 pg/ml in dogs prepared with gastric and duodenal fistulas. Infusion of substance P at 5 ng/kg/min increased circulating hormone concentrations by more than 1 pg/ml and inhibited pentagastrin-stimulated (4 micrograms/kg/hr) gastric acid secretion by 44% (from 10.9 +/- 1.8 to 6.1 +/- 1.6 mEq/30 min); a similar dose of substance P (7 ng/kg/min) did not alter gastrin levels from the basal level of 19.8 +/- 1.2 fmol/ml. Duodenal acidification (with 0.1N HCl at 5 ml/min for 10 minutes) similarly inhibited pentagastrin-stimulated gastric fistula output (from 8.2 +/- 0.9 to an average of 5.0 +/- 0.9 mEq/30 min for the 30 minutes after irrigation) but did not alter circulating substance P levels. Thus, although physiologic concentrations of substance P inhibit gastric fistula output, this peptide does not seem to be involved in the endogenous acid-mediated duodenal control of acid secretion.

Animals↗
PubMed1984

The gastrointestinal tract as an endocrine organ.

During the past several years gastrointestinal endocrinology has expanded its scope. Several specific clinical syndromes can be directly ascribed to abnormalities in the control of the gastrointestinal hormones. New concepts interrelating the gut and the brain have served as a stimulus for investigation of the interactions among control mechanisms in all aspects of human biology. The rapid, almost explosive progress in this area has been spearheaded by surgical physiologists, for which Dr. Graham would have been justly proud. Finally, it is important to spotlight the role that Washington University researchers have played in this developmental process.

Animals↗
PubMed1983

The relationship between the antiviral action of interferon and prostaglandins in virus-infected murine cells.

The relationship between prostaglandins (PG) and interferon (IFN) was investigated. IFN induced the synthesis of immunoreactive PGE and PGA at early and late stages, respectively, of vaccinia virus infection in mouse L fibroblasts. Only species-specific IFN possessed this activity and PG synthesis was stimulated in virus-infected cells, while normal L cells were not affected. The vaccinia virus infection did not significantly alter PG synthesis in the absence of IFN. Indomethacin increased the rate of vaccinia virus replication and partially inhibited the IFN-induced protection of L cells. The addition of exogenous PGA1 only partially reversed this effect. Finally, short-term PGA treatment induced the synthesis of two enzymes (protein kinase and 2,5A synthetase) thought to be partially responsible for the antiviral action of interferon. These findings suggest that a prostaglandin or PG-related compound seems to mediate at least one aspect of IFN action.

2',5'-Oligoadenylate Synthetase↗
PubMed1983

Is thymosin action mediated by prostaglandin release?

Treatment of spleen cells derived from adult thymectomized mice with thymosin fraction 5 resulted in a rapid and dose-dependent stimulation of the release of immunoreactive prostaglandin E2. The release of prostaglandin E2 was associated with induction of theta antigen and was totally inhibited by indomethacin. In contrast, prostaglandin E2 release from spleen cells from intact donors was inhibited by treatment with fraction 5. The data support the concept that prostaglandin E2 mediates the effects of thymosin fraction 5 on lymphocytes.

Animals↗
PubMed1983

The hemodynamic effects of intravenous infusions of serotonin in conscious dogs.

The effects of exogenously infused serotonin on central and regional hemodynamics were investigated in 14 dogs. Using intravenous doses that mimic postprandial levels of serotonin, we were able to demonstrate no changes in cardiac output or mean arterial pressure. However, there were region-specific changes in blood flow. Blood flow to the fundus, antrum, brain, heart, and skeletal muscle were increased by both the low-dose (4 micrograms/kg-min) and the high-dose (10 micrograms/kg-min) infusions. In contrast, blood flow to the kidney, spleen, and liver decreased. Whole blood 5-HT levels were measured in mixed venous blood and systemic arterial blood. Based on the differences between serotonin levels in these two circulations, pulmonary inactivation of exogenously infused serotonin was calculated to be 44%. The half-life of exogenous serotonin was measured at 1.2 min. The data thus suggest that at doses which mimic those released from the intestinal enterochromaffin cells, serotonin may play a role in mediating postprandial hemodynamic responses.

Animals↗
PubMed1983

Cholinergic stimulation of pancreatic polypeptide release by a meal, bombesin, neurotensin, tetragastrin, cholecystokinin, and cerulein.

It has been demonstrated that pancreatic polypeptide (PP) release can be markedly impaired by vagotomy or anticholinergic drugs. The current studies examine the role of cholinomimetic stimulation on PP release in dogs. Eight conscious animals underwent a series of tests: (1) a test meal (10 g/kg Alpo); (2) tetragastrin infusion (4 micrograms/kg/hr); (3) bombesin infusion (1.0 microgram/kg/hr); (4) cerulein infusion (100 ng/kg/hr); (5) cholecystokinin octapeptide (CCK-OP) infusion (100 ng/kg/hr); (6) neurotensin infusion (3 ng/kg/hr). All the studies were repeated individually with intravenous bethanecol (100 micrograms/kg/hr) as the background stimulant. The mean increment of PP released by a meal (160 +/- 32 fmol/ml) was significantly increased by bethanecol infusion (316 +/- 49 fmol/ml) (P less than 0.05). Each individual peptide released a significant amount of PP; tetragastrin: 53 +/- 11; neurotensin: 58 +/- 14; CCK-OP: 42 +/- 9; cerulein: 42 +/- 12; bombesin: 118 +/- 24 (P less than 0.05). Bethanecol did not significantly augment PP release by any of the individual peptides (P greater than 0.05). This study indicates that PP release by a meal is sensitive to cholinomimetic stimulation and that the peptide involved is neither gastrin, neurotensin, CCK, bombesin, nor cerulein. These data support the possibility of the existence of a cholinergic stimulatable mechanism, possibly a peptide responsible for the release of PP.

Animals↗
PubMed1983

The relationship between prostaglandins and virus replication: endogenous prostaglandin synthesis during infection and the effect of exogenous PGA on virus production in different cell lines and in persistently infected cells.

African Green Monkey Kidney cells were shown to normally synthesize immunoreactive PGE1. Infection of these cells with Sendai virus did not alter rates of PGE1 synthesis, while it stimulated interferon production. PGAs, that we have previously shown to be potent inhibitors of Sendai virus replication in this system, at the same dose (4 micrograms/ml), also strongly inhibited the replication of this virus in HEp-2 cells and in VERO cells, a monkey kidney cell line that does not produce interferon. PGA1 was found to be effective in several cell and virus models, suggesting a broad spectrum of antiviral actions. Finally, we confirmed the observation that PGA1-treatment prevents the establishment of a "carrier state" by Sendai virus, and PGA1-cured cells did not show any sign of persistent infection for periods as long as 110 days after Sendai infection. Attempts to cure already established persistently infected cells were only partially successful.

Alprostadil↗
PubMed1983

Inhibition of B-16 melanoma growth in vitro by prostaglandin D2.

Prostaglandin D2 was found to be a potent inhibitor of B-16 melanoma cell replication in vitro. The inhibition was dose-dependent between 3x10(-9)M and 3x10(-6)M (IC50 approximately 0.3 microM after 6 days). On a molar basis, PGD2 was a better inhibitor than PGA2 or 16, 16-dimethyl-PGE2-methyl ester (di-M-PGE2) and in higher concentrations (10(-6)-10(-7)M), comparable to retinoic acid. In higher concentrations, PGD2 inhibited DNA, RNA and protein synthesis. The B-16 melanoma cell line which we used synthesized arachidonic acid metabolites which comigrated with PGA2, PGD2, PGE2, and PGF2 alpha on a thin layer chromatography system.

Animals↗
PubMed1983

Prostaglandin A inhibits the replication of vesicular stomatitis virus: effect on virus glycoprotein.

Prostaglandins of the A series were found to strongly suppress the replication of vesicular stomatitis virus (VSV) in mouse L fibroblasts. The highest non-toxic dose of PGA1, 4 micrograms/ml, decreased VSV production by 93.6%. At this dose, PGA1 did not alter DNA, RNA or protein synthesis in uninfected L cells for periods up to 24 h, whereas it further suppressed protein synthesis and slightly increased RNA synthesis in VSV-infected cells. The presence of PGA1 during virus adsorption, with no treatment after infection, reduced VSV yields by 63.6%. However, the presence of PGA1 during an early step of VSV replication was not essential for the antiviral action to occur (PGA1 treatment could be started 1 to 2 h post-infection). Apart from a slight overall inhibition of virus protein synthesis, PGA1 strongly suppressed the synthesis of the VSV glycoprotein G; moreover, it produced an alteration in the mobility of this protein in SDS-polyacrylamide gels. We propose that this slight decrease in molecular weight (about 4000) of the G protein in the presence of PGA1 could be due to an alteration in the glycosylation process.

Animals↗