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Biomedical subjects

E D Jacobson

Publications and source records attributed to E D Jacobson.

At least 55 records · Page 3Linked to original sources
PubMed1985

Physiology of the splanchnic circulation.

The splanchnic circulation is composed of gastric, small intestinal, colonic, pancreatic, hepatic, and splenic circulations, arranged in parallel with one another. The three major arteries that supply the splanchnic organs, cellac and superior and inferior mesenteric, give rise to smaller arteries that anastomose extensively. The circulation of some splanchnic organs is complicated by the existence of an intramural circulation. Redistribution of total blood flow between intramural vascular circuits may be as important as total blood flow. Numerous extrinsic and intrinsic factors influence the splanchnic circulation. Extrinsic factors include general hemodynamic conditions of the cardiovascular system, autonomic nervous system, and circulating neurohumoral agents. Intrinsic mechanisms include special properties of the vasculature, local metabolites, intrinsic nerves, paracrine substances, and local hormones. The existence of a multiplicity of regulatory mechanisms provides overlapping controls and restricts radical changes in tissue perfusion.

Colon↗
PubMed1985

Action of diltiazem on canine mesenteric artery smooth muscle.

We studied the effects of the Ca++ antagonist diltiazem on the contractile response of isolated first order branches of canine superior mesenteric artery. Maximum contraction induced by 60mM KCl was significantly reduced by 10(-9)M diltiazem and the ED50 concentration of KCl was increased by approximately 30% by the antagonist. Increasing concentrations of diltiazem produced dose-dependent reductions in the maximum contraction and increased the ED50 to KCl indicating mixed competitive and noncompetitive inhibition. Norepinephrine-induced contractions reached a maximum with 10(-5)M of the amine. This response was not altered by 10(-9)M diltiazem; however, the ED50 concentration of norepinephrine was nearly doubled when this concentration of antagonist was used, suggestive of competitive inhibition. Higher concentrations of diltiazem altered both the maximum response and the ED50 of norepinephrine, i.e., the mixed inhibition pattern. However, diltiazem did not alter the response to norepinephrine in Ca++-free medium. These data demonstrate that diltiazem causes relaxation of mesenteric arterial smooth muscle by suppressing Ca++ flux at cell membrane sites but is not influencing intracellular mechanisms of Ca++ release.

Animals↗
PubMed1984

UV-induced mutagenesis at the hypoxanthine-guanine phosphoribosyl transferase locus in two L5178Y mouse lymphoma cell strains with different UV sensitivities.

Two strains of L5178Y mouse lymphoma cells, L5178Y-R (LY-R) and L5178Y-S (LY-S), differ markedly in their sensitivity to 254 nm UV radiation (D0 = 0.7 and 5.5 J/m2; n = 6.0 and 2.0 for LY-R and LY-S cells, respectively). In this study, the frequency of hypoxanthine-guanine-phosphoribosyl-transferase-deficient mutants was determined, using 6-thioguanine (TG) as a selective agent, in populations of LY-R and LY-S cells exposed to various fluences of UV radiation. The spontaneous mutation frequency for LY-R cells was (3.7 +/- 0.6) X 10(-5) TGr mutants per viable cell, and the UV induction rate was (2.2 +/- 0.8) X 10(-4) TGr mutants per viable cell, per J/m2. Both spontaneous and induced mutation frequencies were much lower for LY-S cells. The spontaneous mutation frequency for these cells were too low to make its measurement practicable (less than 0.0013 X 10(-5) TGr mutants per viable cell). Mutation induction rate was (4.2 +/- 2.2) X 10(-7) TGr mutants per viable cell, per J/m2. These differences in mutability do not appear to be due to gene duplication in LY-S cells, or to selective growth disadvantage of LY-S-derived TG-resistant mutants. Possible mechanisms underlying the differences in mutability of LY-R and LY-S cells are considered.

Animals↗
PubMed1984

Effects of nicotine on canine intestinal blood flow and oxygen consumption.

The purpose of this study was to determine the effects of nicotine on intestinal blood flow and oxygen consumption. The intravenous infusion of nicotine at doses corresponding to those experienced by smokers produced a transient increase in systemic arterial blood pressure and mesenteric blood flow. Subsequently a steady-state response developed that consisted of a reduction in mesenteric blood flow due to both a decrease in blood pressure and an increase in intestinal vascular resistance. This increase in resistance was probably due to increased levels of circulating catecholamines. The intra-arterial infusion of nicotine into the intestinal circulation at doses experienced by the average smoker had no effect on either intestinal blood flow or oxygen consumption. Similarly, under in vitro conditions nicotine had no direct effect on intestinal vascular smooth muscle tension. Thus, nicotine appears to reduce intestinal blood flow indirectly as a result of its systemic effects.

Animals↗
PubMed1984

Prostaglandin E1 treatment in experimental acute pancreatitis in the rat.

Prostaglandin E1 (PGE1) was tested for cytoprotective activity against the development of experimental acute pancreatitis in the rat induced by the closed duodenal loop technique. Sham-operated, untreated and PGE1-treated pancreatic rats were investigated. All rats received an initial bolus of 3 ml 5% dextrose in normal saline (D5NS) via jugular catheter 30 min prior to surgery, and a continuous subcutaneous infusion of 35 ml D5NS over 24 h. Each treated rat received 10 micrograms/kg PGE1 in the initial bolus and a maintenance dosage of 10 micrograms/kg/h via the infusate. Serum amylase rose significantly in all pancreatic rats with no significant difference between treated and untreated. Pancreatic edema was more pronounced in PGE1-treated than in untreated rats. The ischemic and autolytic damage to acinar cells and vascular endothelial cells typical of untreated pancreatitis was delayed by PGE1. Mortality rates were unaffected by PGE1.

Acute Disease↗
PubMed1984

Histamine H1 receptor antagonists inhibit autoregulation of renal blood flow in the dog.

Histamine H1 and H2 receptors are present in the canine renal circulation. We have examined the effects of H1 and H2 receptor antagonists on autoregulation of renal blood flow in the dog. Renal arterial pressure was reduced in a step-wise fashion to 80 mm Hg by means of an adjustable aortic clamp positioned above the left renal artery. Infusion of H2 antagonists, cimetidine or ranitidine, into the left renal artery at 10(-5) mol/min had no effect on autoregulation of renal blood flow or on the reactive hyperemia that occurred when the aortic constriction was released. By contrast, intrarenal infusion of 10(-5) mol/min chlorpheniramine, an H1 receptor antagonist, reversibly attenuated reactive hyperemia and the ability of the kidney to autoregulate renal blood flow. Similar results were obtained with other, chemically dissimilar H1 antagonists (terfenadine, diphenhydramine, and pyrilamine). The effects of chlorpheniramine on autoregulation of glomerular filtration rate also were evaluated. Before chlorpheniramine was infused (at 10(-5) mol/min), the reduction of renal arterial pressure to 90 mm Hg had no effect on the glomerular filtration rate, whereas, during infusion of the H1 antagonist, the glomerular filtration rate fell significantly when renal arterial pressure was reduced to 90 mm Hg. Infusion of histamine (1 microgram/kg per min) with increasing amounts of cimetidine, chlorpheniramine, diphenhydramine, or pyrilamine resulted in virtually identical dose-dependent decreases in histamine-induced renal vasodilation. However, even with 10(-5) mol/min cimetidine or 10(-5) mol/min chlorpheniramine, diphenhydramine, or pyrilamine, a significant histamine-induced renal vasodilation was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1984

Hemodynamic actions of nicotine on the canine stomach.

Acute effects of nicotine were determined in the circulation of the stomach in which measurements of gastric blood flow, systemic arterial and portal venous blood pressures, and the arteriovenous oxygen content difference were made. From these measurements gastric vascular resistance and oxygen consumption were calculated. Nicotine was infused for 10-min periods in two doses intraarterially (ia) and intravenously (iv) alone and following adrenergic receptor blockade with either propranolol or phentolamine or both agents. With ia nicotine alone, gastric blood flow and oxygen consumption increased. The effect of nicotine on blood flow was enhanced by prior treatment with phentolamine. The effects of nicotine on both blood flow and oxygen consumption were abolished in the presence of combined phentolamine plus propranolol. With iv nicotine alone, gastric blood flow, oxygen consumption, and arterial pressure increased transiently. Phentolamine enhanced the effect of nicotine on oxygen uptake and prevented the pressor response. Propranolol enhanced the pressor effect of nicotine but abolished the blood flow and oxygen consumption responses. Combined treatment with both adrenergic antagonists abolished nicotine effects on blood flow and oxygen consumption. These findings indicate that nicotine alters gastric hemodynamics and oxygen consumption during acute intravascular infusions of the drug. The vasodilator and metabolic effects of nicotine appear to be mediated via beta-adrenergic receptors. These findings provide little basis for implicating a local ischemic mechanism in the ulcerogenic effects of nicotine on the stomach.

Animals↗
PubMed1984

X-ray and UV mutagenesis in two L5178Y cell strains differing in tumorigenicity, radiosensitivity, and DNA repair.

L5178Y-R (LY-R) and L5178Y-S (LY-S) cells are inversely cross sensitive to X-rays and UV (254 nm) radiation (Dox = 0.94 and 0.69 Gy, Dqx = 0.32 and 0.010 Gy; Douv = 0.07 and 5.5 J m-2, Dquv = 3.8 and 1.6 J m-2, for LY-R and LY-S cells, respectively). Mutagenicity of the two cell strains at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus was examined using 6-thioguanine resistance as a marker. LY-S cells showed remarkably low mutability; the spontaneous mutation frequency of LY-S cells was at least two orders of magnitude lower than that for LY-R cells (less than or equal to 0.005 vs. approximately 2.5 mutants per 10(5) survivors). The induced mutation rates for X-rays were 0.95 +/- 0.14 and 0.35 +/- 0.09 mutants per Gy per 10(5) survivors, and for UV radiation, 21.5 +/- 8.2 and 0.04 +/- 0.02 mutants per J m-2 per 10(5) survivors, for LY-R and LY-S cells, respectively. The results suggest that LY-S cells are efficient in the repair of UV-induced damage but not of lesions produced by ionizing radiation. The reverse appears to be true for LY-R cells. In addition, the low mutability of LY-S cells suggests that the processing of pre-mutational lesions may lead to lethality in this strain.

Animals↗
PubMed1984

Decrease in alkaline secretion during duodenal ulceration induced by mepirizole in rats.

The mechanisms by which the potent antiinflammatory agent, mepirizole, causes duodenal ulceration were investigated in the rat. After subcutaneous administration of 200 mg/kg of mepirizole, basal gastric acid secretion remained unchanged for 5 h but duodenal alkaline output, reliably measured, decreased significantly (p less than 0.05) within 2 h. The decrease was maximal (-45%) at 3 h and persisted for a total of 6 h. The duodenal alkaline secretion returned to near normal by 24 h. A dose-response study showed that the threshold ulcerogenic dose of mepirizole (30 mg/kg) did not significantly reduce alkaline secretion, whereas higher doses did. Plasma levels of immunoreactivity of gastrin, pancreatic polypeptide, vasoactive intestinal polypeptide, and secretin were not changed at either 6 or 24 h after oral mepirizole. Vasoactive intestinal peptide levels in the duodenal mucosa were increased by 158% at 24 h after administration. Secretin levels in the duodenal mucosa were decreased by greater than 60% at both 6 and 24 h after drug treatment. Intravenous secretin (1 CU/kg X h) had no effect on duodenal alkaline secretion in either saline- (154 mM NaCl) or mepirizole-treated animals. Exogenous 16,16-dimethyl prostaglandin E2 (10 micrograms/kg X h, i.v.) reversed the action of mepirizole on duodenal alkaline secretion. These findings suggest that mepirizole causes a reduction in duodenal alkaline secretion that can be reversed by administration of an exogenous prostaglandin.

16,16-Dimethylprostaglandin E2↗
PubMed1983

Intestinal blood flow and oxygen consumption.

In this study, we examined the effects of both pharmacologically and mechanically induced increases in intestinal blood flow on intestinal oxygen consumption. Intraarterial infusions of prostacyclin (1-20 ng X kg-1 X min-1) significantly increased both blood flow and oxygen consumption under free flow conditions. However, the increase in oxygen consumption appears to be due to the corresponding increase in blood flow rather than a direct effect of prostacyclin on intestinal metabolism. This conclusion is supported by the finding that a mechanically induced increase in intestinal blood flow (60%) can also produce an increase in intestinal oxygen consumption (24%). These findings support the hypothesis that intestinal oxygen consumption is flow-dependent over a wide range of blood flows.

Animals↗
PubMed1982

Nonocclusive intestinal ischemia treated with intraarterial infusion of prostaglandin E1.

An elderly woman with a history of cardiac failure treated with digitalis had both abdominal pain and dehydration. Parenteral fluid and electrolyte support failed to alleviate abdominal pain. Superior mesenteric arteriography combined with "spillover" method of estimating blood flow revealed an intestinal nonocclusive ischemic state which was treated successfully with 44-hour intraarterial infusion of prostaglandin E1. Laparotomy performed during the drug infusion revealed viable intestine.

Aged↗
PubMed1982

Host cell reactivation by excision repair is error-free in human cells.

Do host cell repair processes affect the mutagenesis of UV-irradiated virus in human cells? The answer was obtained by investigating the mutagenesis of UV-irradiated herpes simplex virus after the irradiated virus was grown in human cells that possess normal repair capacity (normal) or lack excision repair (XPA) or post-replication repair (XP var). Evidence is presented which indicate that XPA cells express no host cell reactivation, while XP var cells express the normal level. Viral mutagenesis was measured as the fraction of the progeny of the surviving virus capable of plaque formation in the presence of iododeoxycytidine. In the normal and XPA cells mutagenesis of the irradiated virus increased linearly with UV exposure. The UV exposure needed to yield a given mutagenesis level for virus grown in XPA cells was much lower than that for virus grown in normal cells. However, when the mutation frequencies were compared at similar virus survival levels, the data from virus grown in normal cells and in XPA cells were indistinguishable. Mutagenesis in XP var cells increased as dose squared and was similar in magnitude to that in normal cells. Thus the excision repair of normal cells which provided host cell reactivation by removing lethal UV damage also removed mutagenic lesions from the virus with the same efficiency, while the repair deficiency of XP var cells had a minor role in host cell reactivation and in mutagenesis. This demonstrates that in human cells host cell reactivation by excision repair is primarily an error-free process.

Cell Line↗