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Biomedical subjects

L Levine

Publications and source records attributed to L Levine.

At least 199 records · Page 11Linked to original sources
PubMed1980

PGI2-specific antibodies administered in vivo suggest against a role for endogenous PGI2 as a circulating vasodepressor hormone in the normotensive and spontaneously hypertensive rat.

Immunoglobulins raised against 5,6-dihydro PGI2 crossreact with PGI2. When infused in vivo into the rat, these immunoglobulins are capable of 1) neutralising the vasodepressor effects (bolus or continuous infusion) of exogenous PGI2, 2) blocking the catabolism of exogenous 3H-PGI2 and prolonging its life-time in the circulation (t 1/2 approx 60 min) while that of 3H-PGE2 is unaffected, 3) trapping an endogenously produced substance which after extraction from blood and dissociation from the ligand-antibody complex, is immunoreactive with 6-keto PGF1 alpha-specific antiserum. Yet the anti-5,6-dihydro PGI2 immunoglobulins have no effect on resting arterial blood pressure both in the normotensive and spontaneously hypertensive rat. These experiments indicate that endogenously produced PGI2 does not play a significant systemic role in blood pressure control although in combination with other vasodilators it could still participate in the regulation of vascular tone at a local level.

Angiotensin II↗
PubMed1980

The development of a radioimmunoassay for 12-L-hydroxyeicosatetraenoic acid.

Antibodies directed toward 12-L-hydroxyeicosatetraenoic acid (12-L-HETE) were generated in rabbits by immunization with conjugates of 12-L-HETE and human serum albumin. The concentration of antibodies was determined by incubating immune plasma with 12-L-HETE that had been covalently linked to a solid support, washing the 12-L-HETE support, and measuring the quantity of bound antibodies by reaction with [125I]Protein A. The addition of 0.5 ng-10 ng of fluid-phase 12-L-HETE to the standard mixture of solid-phase 12-L-HETE and anti-12-L-HETE plasma inhibited by 21-80% the binding of antibodies and consequently of [125I]Protein A to the solid support. The 12-OH function positioned between two double bonds was the immunodominant determinant of this antigen-antibody reaction, but the carboxyl function also was recognized. This radioimmunoassay was used to detect and quantitate 12-L-HETE resolved by high pressure liquid chromatography.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1980

N-(4-hydroxyphenyl)retinamide: a synthetic analog of vitamin A that is a potent inhibitor of prostaglandin biosynthesis.

In Madin-Darby canine kidney (MDCK) cells, 4-hydroxyphenyl retinamide, at levels ranging from 0.025 to 3.1 microM, inhibited serum- and TPA-stimulated biosynthesis of prostaglandin F2 alpha, prostaglanding I2 (measured as 6-keto-prostaglandin F1 alpha) and prostaglandin E2 but did not inhibit serum- or TPA-stimulated deacylation of cellular phospholipids. 4-Hydroxyphenyl retinamide was also a potent inhibitor of prostaglandin E2 and prostaglandin F2 alpha production by serum-stimulated methylcholanthrene-transformed mouse fibroblasts (MC5-5), normal human fibroblasts (D-550), "spindle-shaped" smooth muscle cells present in the intima layer of rabbit aorta (R-1), and thromboxane production by melittin-stimulated mouse lymphoma cells (WEHI-5). In the presence of 10% fetal bovine serum, 4-hydroxyphenyl retinamide inhibited prostaglandin production by MDCK cells 4 times less effectively than indomethacin and about 50 times more effectively than aspirin; while in the absence of serum, the inhibiting effectiveness of 4-hydroxyphenyl retinamide was equal to that of indomethacin.

Animals↗
PubMed1980

Analysis by high performance liquid chromatography of cyclooxygenase products of arachidonic acid metabolism in plasma of rabbits bearing the VX2 carcinoma.

Cyclooxygenase products of arachidonic acid metabolism in the plasma of normal rabbits and animals bearing the VX2 carcinoma were separated by high performance liquid chromatography and the effluent fractions assayed by serologic methods. The products measured were 6-keto-PGF1 alpha, thromboxane B2, PGE2, PGF2 alpha, 13,14-dihydro-PGE2, 13,14-dihydro-15-keto-PGE2, 15-keto-PGE2, and 13,14-dihydro-15-keto-PGF2 alpha. In hypercalcemic, tumor-bearing rabbits, the plasma concentrations of 13,14-dihydro-15-keto-PGE2 and 13,14-dihydro-15-keto-PGF2 alpha were markedly elevated (in the range of 0.5 to 16 ng/ml). Previously unmeasured 6-keto-PGF1 alpha, thromboxane B2, 13,14-dihydro-PGE2 and 15-keto-PGE2 were not found in high concentrations in the plasma of tumor-bearing rabbits. These results add further support to our conclusion that the VX2 tumor produces hypercalcemia in the host by a mechanism which utilizes PGE2, rather than a subsequent metabolite of this prostaglandin, as the mediator between the neoplasm and bone.

Animals↗
PubMed1980

Prostaglandin production by minced carrageenin granuloma tissue of rats and its inhibition by dexamethasone and cycloheximide.

Seven-day-old carrageenin granuloma tissue of rats, when incubated in organ culture, produced 6-keto-prostaglandin F1 alpha, prostaglandin E2, prostaglandin F2 alpha, and thromboxane B2 in ratios of 16/7/1/1, respectively. Indomethacin (1 microgram/ml) inhibited this cyclooxygenase-mediated arachidonic acid metabolism. Dexamethasone (1 microgram/ml) also inhibited this metabolic cascade. Its inhibitory effect was not immediate; preincubation of the tissue with dexamethasone potentiated its inhibitory effectiveness. Cycloheximide (0.1 to 10 microgram/ml) also inhibited prostaglandin production. The inhibitory mechanism by cycloheximide of prostaglandin production was discussed in relation to that by dexamethasone.

6-Ketoprostaglandin F1 alpha↗
PubMed1980

The synthesis of prostaglandins by bovine cerebral microvessels.

Bovine cerebral microvessels (arterioles and capillaries) synthesize prostacyclin (PGI2, measured as 6-keto PGF1 alpha), PGF2 alpha, PGE2 and thromboxane A2 (measured as TXB2) when incubated in glucose-bicarbonate buffer for 30 minutes. Rapid freezing and thawing decreased the subsequent synthesis of 6-keto PGF1 alpha by cerebral microvessels and raised the basal levels of this metabolite within the incubation medium. At low concentrations, the addition of arachidonic acid (0.16 microM) did not stimulate prostacyclin or prostaglandin production; at higher concentrations (16 microM), the synthesis of PGI2 and PGF2 alpha was inhibited. Activation of lipase by the peptide melittin stimulated the synthesis of all arachidonic acid metabolites to the same extent. Thus cerebral microvessels deacylate cellular lipids and metabolize endogenous arachidonic acid to form prostaglandins, prostacyclin and related compounds as previously demonstrated in larger blood vessels. The synthesis and release of these molecules may be important for modulating the tone and reactivity of small blood vessels within the brain.

Animals↗
PubMed1980

Delayed puberty in males with chronic renal failure.

The effects of chronic renal failure on the pituitary-testicular axis of 31 males, aged 11.7 to 20.0 yr (mean, 16.0 yr) were studied. Nine patients not on hemodialysis (group I) had serum creatinines between 2.5 and 8.0 mg/dl, 10 patients were on hemodialysis (group II) and 12 patients had received a renal transplant (group III). The Tanner stage of pubertal development was delayed relative to chronologic age. Testosterone (T), delta 4-androstenedione (delta 4), and urinary 17-keto steroids were normal when related to pubertal stage in groups I and II; and dehydroepiandrosterone (DHEA) and DHEA sulfate (DS) were in the low normal range. In group III, adrenal androgens (delta 4, DHEA, DS) were decreased as a consequence of prednisone therapy whereas T was normal. Luteinizing hormone levels were normal in all. Follicle-stimulating hormone levels were normal in all. Follicle-stimulating hormone (FSH) was significantly increased in groups I and II. In group III, FSH was normal in 6 of 9 patients with serum creatinine concentrations < 2 mg/dl. FSH levels were uniformly elevated in Tanner I-V patients with creatinines > 2 mg/dl. The data shows that FSH is elevated in patients with chronic renal failure even in prepuberty and early adolescence. This may reflect damage to germinal epithelium prior to the advent of spermatogenesis, whereas Leydig cell function appears to remain intact.

Adolescent↗
PubMed1980

Increase in prostaglandins during converting enzyme inhibition.

1. Because changes in the plasma concentration of angiotensin II and bradykinin appear inadequate to account completely for the hypotensive response to captopril, we measured changes in plasma prostaglandins in response to increasing doses of captopril in nine supine normal male subjects studied on both a high (200 mol/l) and low (10 mol/l) sodium intake. 2. On both the high and low sodium diets, captopril induced significant (P < 0.01) increments in the 13,14-dihydro-15-keto metabolite of the vasodilatory prostaglandin E2, which correlated significantly with the fall in blood pressure (P < 0.0001). 3. No significant changes were noted in the plasma levels of 6-keto-prostaglandins F1 alpha or thromboxane B2, the stable products of prostacyclin and thromboxane A2 respectively.

Adult↗
PubMed1980

Accumulation of cyclooxygenase products of arachidonic acid metabolism in gerbil brain during reperfusion after bilateral common carotid artery occlusion.

Several of the cyclooxygenase products of arachidonic acid were measured in the cerebral hemispheres of gerbils subjected to transient interruption of the cerebral circulation. The levels of PGD2, PGF2 alpha, PGE2, TXB2, 13, 14-H2-15-keto-PGE2, and the stable nonenzymic product of prostacyclin, 6-keto-PGF1 alpha, were not altered at the end of a 5-min period of ischemia. However, the onset of reperfusion was accompanied by a rapid accumulation of these products. Levels were highest during the initial period of reperfusion, then decreased to approach control levels after 120 min. PGD2, PGF2 alpha, and PGE2 were the predominant metabolites detected. This postischemic accumulation of arachidonic acid metabolites could be blocked by prior administration of inhibitors of cyclooxygenase activity.

Animals↗
PubMed1980

Captopril-induced changes in prostaglandin production: relationship to vascular responses in normal man.

Captopril is a potent hypotensive agent whose efficacy has hitherto been attributed to its ability to alter either angiotensin II formation or kinin degradation. Our purpose was to examine captopril's acute effect on prostaglandin production, because changes in neither the renin-angiotensin nor the kallikrein-kinin systems appear adequate to account for the fall in arterial pressure. The plasma levels of angiotensin II, kinins, and prostaglandins were determined in response to increasing doses (5, 12.5, and 25 mg) of captopril and these responses were compared with the change in arterial pressure observed in nine supine normal male subjects studied on both a high (200 meq) and low (10 meq) sodium intake.Captopril significantly (P < 0.01) increased the levels of the 13,14-dihydro-15-keto metabolite of prostaglandin E(2) (PGE(2)-M), a potent vasodilator, with similar responses being observed on both a high and a low sodium intake. No significant changes in the plasma levels of 6-keto-prostaglandin F (1)alpha, or thromboxane B(2), the stable products of prostacyclin and thromboxane A(2), respectively, occurred. The depressor response to captopril correlated with the change in PGE(2)-M (r = 0.52, t = 5.44, P < 0.0001). On the other hand, although significant (P < 0.02) decrements in angiotensin II and increments in plasma kinins accompanied the hypotensive response in sodium-restricted subjects, in sodium-loaded subjects where the renin-angiotensin system was suppressed, no change in angiotensin II, and only a modest change in kinins was noted, even though significant (P < 0.01) decrements in diastolic blood pressure occurred (-10+/-2 mm Hg).Thus, changes in depressor prostaglandin production can better account for the hypotensive response to captopril, thereby extending to yet another vasoactive system an influence by this class of drugs and providing a new approach to dissecting the abnormality in the control of vascular tone in patients with hypertension.

Adult↗
PubMed1980

Preparation of [3H]-12-L-hydroxyeicosatetraenoic acid and its use in radioimmunoassay.

An efficient method for the enzymic preparation of high specific radioactivity [3H]-12-L-hydroxyeicosatetraenoic acid (12-L-HETE) is described. This compound was used as a radiolabeled ligand in the radioimmunoassay (RIA) of 12-L-HETE. The accuracy of the RIA was checked by incubating [14C]arachidonic acid with platelet lipoxygenase, and measuring enzyme activity in the presence of the inhibitor, 1-phenyl-3-pyrazolidinone (phenidone). The amount of 12-L-HETE synthesized, determined by RIA, was found to be in agreement with that analyzed by radiochemical assay after thin layer plate chromatography.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗