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Biomedical subjects

D M Cohen

Publications and source records attributed to D M Cohen.

At least 127 records · Page 7Linked to original sources
PubMed1984

Pancreatic hormone profiles and metabolism posthepatectomy in the dog. Evidence for a hepatotrophic role of insulin, glucagon, and pancreatic polypeptide.

Gut-related peptide hormones, especially insulin and glucagon, have been implicated in promoting hepatic regeneration. To elucidate the interrelationship between pancreatic peptide hormones and hepatic regenerative activity, we evaluated pancreatic hormone levels and their metabolism before and over a 15-day period after limited (42%) and extended (72%) hepatectomy in the dog. Serum insulin, glucagon, and pancreatic polypeptide levels increased significantly after both limited and extended hepatectomy but not after sham laparotomy. In the case of glucagon only, these increases were related to the extent of liver resection. No significant changes in plasma somatostatin levels were observed posthepatectomy. Plasma glucose levels remained normal throughout the period of study. Metabolic clearance rates and plasma half-lives for insulin, glucagon, and pancreatic polypeptide did not change over the study period. Peripheral C-peptide/insulin molar ratios were unchanged posthepatectomy, indicating no change in hepatic insulin extraction. In the absence of demonstrable changes in hormone metabolism or metabolic stimuli to secretion, these increases in pancreatic hormone levels, coinciding with the period of known maximal hepatic regenerative activity, are compatible with the notion that these are hepatotrophic responses, which could conceivably be mediated by humoral feedback signals from the liver to the endocrine pancreas.

Animals↗
PubMed1984

Antihypertensive effects of CI-907 (indolapril): a novel nonsulfhydryl angiotensin converting enzyme inhibitor.

CI-907 is a new orally active nonsulfhydryl angiotensin converting enzyme (ACE) inhibitor. Monoester (prodrug) and diacid forms produced concentration related ACE inhibition in guinea-pig serum (IC50 for monoester, 1.7 X 10(-7) M and for diacid, 2.6 X 10(-9) M). In isolated rabbit aortic rings and in rat and dog autonomic studies, CI-907 is highly specific in suppressing the contractile or pressor responses to angiotensin I. In two-kidney, one-clip Goldblatt hypertensive rats, single daily doses (0.03-30 mg/kg p.o.) produced dose-dependent decreases in blood pressure; 3 mg/kg lowered blood pressure to normotensive levels. In the spontaneously hypertensive rat, subacute administration of CI-907 (30 mg/kg/day for 5 days) produced the same decrease in blood pressure as that obtained in the renal hypertensive rat. In diuretic-pretreated renal hypertensive dogs, 10 mg/kg normalized blood pressure. For equivalent drops in blood pressure, heart rate increases were less in CI-907 than in enalapril-treated renal hypertensive dogs. No side effects were observed with CI-907 in any of the conscious animals. The antihypertensive response to CI-907 (0.03-1.0 mg/kg p.o.) was found to correlate with inhibition of vascular tissue ACE, but not plasma or brain ACE in two-kidney, one-clip renal hypertensive rats. These studies indicate that CI-907 is a potent antihypertensive agent with a heart rate profile different from enalapril.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1984

CI-906 and CI-907: new orally active nonsulfhydryl angiotensin-converting enzyme inhibitors.

CI-906, [3S-[2[R*(R*)]], 3R*]-2-[2-[[1-(ethoxycarbonyl)-3-phenylpropyl]-amino]-1-oxopropyl] 1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid, monohydrochloride, and CI-907, [2S-[1[R*(R*)]], 2 alpha, 3a beta, 7a 7a beta]-1-[2-[[1-(ethoxycarbonyl)-3-phenylpropyl]amino] 1-oxopropyl]octahydro-1H-indole-2-carboxylic acid, monohydrochloride, are two new nonsulfhydryl-type angiotensin-converting enzyme (ACE) inhibitors. Monoester (prodrug) and diacid forms produced concentration-related ACE inhibition in guinea pig serum (IC50 for CI-906 = 8.3 X 10(-9) M, diacid = 2.8 X 10(-9) M; CI-907 = 1.0 X 10(-7) M, diacid = 2.6 X 10(-9) M). In isolated rabbit aortic rings and in in vivo rat and dog autonomic studies, both compounds were highly specific in suppressing the contractile or pressor responses to angiotensin I. In two-kidney, one-clip Goldblatt (renin-dependent) hypertensive rats there was a good correlation between the inhibition of vascular converting enzyme and blood pressure lowering and a poor correlation between blood pressure lowering and plasma and brain converting enzyme inhibition. Cardiovascular, pulmonary, and central nervous system performance evaluations showed no side effects or gross toxicity. The preclinical profile shows CI-906 and CI-907 to be specific, potent, orally active ACE inhibitors. They are expected to have therapeutic utility in hypertension and in any other condition where converting enzyme inhibition would be useful.

Angiotensin I↗
PubMed1984

Antihypertensive profile of the angiotensin-converting enzyme inhibitors CI-906 and CI-907.

CI-906 and CI-907, new orally active nonsulfhydryl angiotensin-converting enzyme inhibitors, were examined for antihypertensive effects in unanesthetized hypertensive rats and dogs. In two-kidney, one-clip Goldblatt hypertensive rats, single oral daily doses (0.03-30 mg/kg) produced dose-dependent decreases in blood pressure; a single 3 mg/kg oral dose lowered blood pressure to normotensive levels. In spontaneously hypertensive rats, 30 mg/(kg X day) orally administered for 5 consecutive days achieved the same blood pressure decrease as that obtained on the first day in the renal hypertensive rats. In diuretic-pretreated renal hypertensive dogs, a 10 mg/kg oral dose decreased blood pressure by 25%. No adverse side effects were observed with CI-906 and CI-907 in any of the conscious animals. These studies indicate that CI-906 and CI-907 are potent, orally active antihypertensive agents without any apparent limiting side effects.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1983

Potassium-induced vascular relaxation in two kidney-one clip, renal hypertensive rats.

This study was designed to characterize potassium-induced relaxation in vascular smooth muscle in two kidney-one clip (2K-1C), renal hypertensive rats. Potassium-induced relaxation was evaluated in the isolated tail artery and in the isolated pump perfused renal vasculature. Both preparations relaxed in response to potassium after contraction induced by norepinephrine in potassium-free solution. Arterial preparations from hypertensive rats showed greater relaxation than did those from normotensive rats. Potassium-induced relaxation in tail arteries from hypertensive rats was more sensitive to ouabain inhibition than those from normotensive rats; the renal vasculature of hypertensive rats did not differ from controls with respect to ouabain sensitivity. Relaxation in response to potassium in isolated tail artery segments varied with the: 1. length of incubation in potassium-free solution; 2. concentration of added potassium; and 3. concentration of norepinephrine added during the potassium-free interval. The amplitude of potassium relaxation is believed to be a functional measure of the electrogenic sodium pump. These experiments support the hypothesis that vascular smooth muscle from 2K-1C renal hypertensive rats has increased electrogenic sodium pump activity, in vitro.

Animals↗
PubMed1983

Management of pancreatic trauma.

Twenty patients who sustained pancreatic trauma are reviewed. Eighteen of the patients underwent emergency laparotomy and there were 53 major associated injuries. Three patients died, giving an operative mortality of 17%. All deaths could be directly attributed to the severity and extent of the associated injuries. Eleven of the 15 survivors following emergency operation developed serious postoperative complications which, in 6 instances, were directly related to the pancreatic injury. Two patients were initially treated conservatively because the isolated pancreatic injuries were missed. Both developed complications requiring operation.

Adolescent↗
PubMed1983

Survey of new antihypertensive drugs: 1982.

Over 500 compounds reported to have antihypertensive activity have been cataloged from the world literature (1979-1982). The agents were classified according to mechanism: 1) drugs interacting at alpha-adrenoceptor sites; 2) beta-adrenoceptor antagonists; 3) drugs interacting with the autonomic nervous system by mechanisms other than 1 and 2; 4) inhibitors of the renin-angiotensin system; 5) diuretics; 6) vasodilator antihypertensives; and 7) drugs with miscellaneous mechanisms and/or sites of action. Within each class the drugs were subclassified and compounds that best fit the prototypes identified. The scheme is subjective, largely because of conflicting information cited in the literature. It is clear that many new drugs are at various stages of development. Whether or not these drugs will survive the scrutiny of rigorous and lengthy preclinical and clinical development, and in fact prove to be better antihypertensive agents than the currently marketed agents, remains to be established.

Antihypertensive Agents↗
PubMed1982

Systemic sarcoidosis presenting with Horner's syndrome and mandibular paresthesia.

A patient with Stage I systemic sarcoid (affecting the mediastinum and cervical lymph nodes) is presented. This patient had ptosis of the eyelid and miosis (Horner's syndrome) due to involvement of the cervical-thoracic sympathetic nerves by the granulomatous process. Bony destruction simulating periodontal disease occurred in the molar-premolar region and caused pain and paresthesia. Systemic sarcoid may occur more commonly in the jaws than reported cases would indicate. Sarcoidosis should be considered in the differential diagnosis when periodontal disease appears refractory to local therapy.

Diagnosis, Differential↗
PubMed1982

Ectopic soft-tissue mesiodens.

The mesiodens is the most common supernumerary tooth. It can be found in both the erupted and the impacted states. A case of a developing mesiodens located entirely in soft tissue is described. The lesion presented as a pedunculated palatal mass. No case of soft-tissue mesiodens has been previously reported. A theory of origin for this supernumerary tooth is proposed.

Child, Preschool↗
PubMed1979

Chemistry of heparitin sulfate and heparin from normal tissues and from patients with Hunter syndrome.

Some structural features of heparitin sulfate excreted by patients with Hunter syndrome are described. It is shown, with the aid of heparitinases and heparinase from Flavobacterium heparinum, that the Hunter heparitin sulfate is a very complex structure composed of nine different disaccharide units containing regions akin to normal heparitin sulfate and regions akin the heparin. Two-thirds of the iduronic acid residues of Hunter heparitin sulfate are devoid of sulfate, contrasting with heparin in which most of the iduronic acid residues are sulfated. The isolation and characterization of the non-reducing ends of heparin and of the heparitin sulfates is also described. Based on these results the specificity of the heparinase and heparitinases as well as the biosynthesis of iduronic acid-containing heparin-like compounds is discussed.

Chemical Phenomena↗
PubMed1979

Phosphoethanolamine as a growth factor of a mammary carcinoma cell line of rat.

We have identified phosphoethanolamine as the pituitary-derived growth-promoting material that specifically stimulates the rat mammary carcinoma cell line 64-24. We have been studying the growth characteristics of the 64-24 cell line, which was isolated from a highly hormone-dependent tumor and which retains in culture many characteristics of the original tumor. Previously, crude bovine pituitary extract was shown to contain a significant amount of growth-stimulating activity for these cells, and a growth factor from this extract was purified to homogeneity. This report describes the identification of the growth factor as phosphoethanolamine. Further, the biological activity of phosphoethanolamine was found to be virtually identical to that of the purified growth factor. A possible role of phosphoethanolamine in the growth of mammary tumor cells as well as of normal mammary epithelial cells and other tissues is discussed.

Animals↗
PubMed1979

Cellular thin filament protein contents and force generation in porcine arteries and veins.

We estimated the cellular myosin, actin, and tropomyosin contents of vascular smooth muscle from (1) seven major arteries, (2) seven large veins, and (3) the first through third order branches of the uterine vasculature to determine whether variations in the contractile apparatus contribute to the functional diversity of vascular smooth muscle. We obtained the estimates by quantitative densitometry of stained polyacrylamide gels after electrophoresis of sodium dodecyl sulfate-treated tissue homogenates. No differences in cellular myosin content were found (18.7 +/- 1.0 mg/g cell wet weight in arteries vs. 17.2 +/- 0.7 in veins). However, the actin and tropomyosin contents were higher in arteries (49.7 +/- 2.9 and 13.1 +/- 0.8 mg/g cell, respectively) than in veins (25.5 +/- 1.4 and 7.0 +/- 0.3 mg/g cell). These differences persisted in the smaller uterine vessels. The higher contents of thin filament proteins in arteries, compared with veins and several other smooth muscle tissues previously studied, may underlie the high force generating capacity of arterial smooth muscle.

Actins↗
PubMed1978

Differences in cellular contractile protein contents among porcine smooth muscles: evidence for variation in the contractile system.

Cellular myosin, actin, and tropomyosin contents and ratios were determined for arterial (carotid, aorta, and coronary), intestinal (circular and longitudinal), esophageal, uterine, and tracheal smooth muscles inthe pig. Tissue protein contents were estimated by densitometry of polyacrylamide gels after electrophoresis of sodium dodecyl sulfate-treated tissue homogenates. Cellular contractile protein contents were estimated by correction for extracellular spaces. Cellular myosin contents were similar in each tissue (average +/- 1 SEM = 19.6 +/- 0.8 mg/g cell wet wt). However, the cellular contents of the thin filament proteins, actin and tropomyosin, were significantly higher in the arteries than in the nonarterial tissues. The calculated weight ratios of actin: myosin averaged 2.6 +/- 0.2 in the three arterial tissues and 1.5 +/- 0.1 in the nonarterial tissues, which may be compared with 0.36 in vertebrate striated muscles. The actin:tropomyosin weight ratios for all tissues were 3.7 +/- 0.1, a value comparable to the skeletal muscle ratio. The physiological implications of variations in the cellular thin filament protein contents are unknown, but these variations probably contribute to the observed differences in contractile function among various smooth muscles.

Actins↗
PubMed1977

Differentiation of mucopolysaccharidoses by analyses of the excreted sulfated mucopolysaccharides.

Analyses of sulfated mucopolysaccharides excreted by patients with Hunter, Hurler, Scheie, Sanfilippo A and Sanfilippo B syndromes are reported. Three distinct methods, namely agarose gel electrophoresis, enzymatic degradation and molecular weight determination, were used in an attempt to differentiate the mucopolysaccharidoses by analysis of the urinary mucopolysaccharides. It is shown that by the combination of these methods it is possible to differentiate most of the syndromes and also to demonstrated that some patients with the same syndrome excrete different types of sulfated mucopolysaccharides.

Diagnosis, Differential↗