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Biomedical subjects

L Levine

Publications and source records attributed to L Levine.

At least 55 records · Page 3Linked to original sources
PubMed1994

Alpha-thrombin and trypsin use different receptors to stimulate arachidonic acid metabolism.

Rat liver cells (the C-9 cell line) are stimulated to metabolize arachidonic acid by alpha-thrombin, its receptor polypeptide, gamma-thrombin, and trypsin. Prostaglandin (PG) I2 synthesis stimulated by alpha-thrombin is inhibited by dansylarginine N-(3-ethyl-1,5-pentanediyl) amide (DAPA), by hirudin, by the synthetic tyrosine-sulfated dodecapeptide corresponding to residues 53-64 of hirudin (hirugen), by the Tyr(SO3H)63-hirudin fragment 54-65 and by rabbit lung thrombomodulin. Stimulation of arachidonic acid metabolism by the receptor octapeptide, SFLLRNPN, is not affected by DAPA or hirudin. gamma-Thrombin stimulates arachidonic acid metabolism but at 300 to 400-fold higher concentrations. Trypsin stimulates arachidonic acid metabolism. Trypsin's proteolytic activity is required--its ability to stimulate is abolished if it is incubated with Na-p-tosyl-L-lysine chloromethyl ketone (TLCK) or bovine pancreatic trypsin inhibitor. Prior treatment of the rat liver cells with alpha-thrombin blocks subsequent stimulation by alpha-thrombin, but not by trypsin, whereas prior treatment with trypsin blocks subsequent stimulation by trypsin, but not the activity stimulated by alpha-thrombin. Prior treatment of the cells with the serine-proteases, chymotrypsin, pancreatic or neutrophil elastase and thrombocytin from Bothrups atrox venom, block alpha-thrombin's activation of PGI2 production, but not the activity stimulated by trypsin. These findings indicate that alpha-thrombin and trypsin stimulate PGI2 production via different receptors.

Amino Acid Sequence↗
PubMed1994

Short report: a comparative study of the interaction between antacid and H2-receptor antagonists.

The influence of concomitant antacid administration on the relative bioavailability of the H2-receptor antagonists cimetidine, famotidine, nizatidine and ranitidine, was investigated in a panel of 21 healthy, adult male volunteers in an eight-way crossover trial. Administration with antacid reduced the bioavailability of all agents tested. The reduction in area under the serum concentration-time curve (AUC) was greatest for cimetidine (23%) and ranitidine (26%) and least for nizatidine (12%) and famotidine (19%). Reductions in peak serum concentration (Cmax) followed a similar pattern. The times of peak serum concentrations were not affected by antacid. Comparison of the relative bioavailability among all drugs tested showed no statistically significant differences in the effect of antacid administration on these agents. However, a high degree of intersubject variability was observed.

Adult↗
PubMed1994

Drug interactions of H2-receptor antagonists.

Three drug interactions of nizatidine and of other antisecretory agents were studied comparatively. First, the effects of nizatidine, cimetidine and ranitidine on the dispositional kinetics of theophylline were evaluated in chronic obstructive pulmonary disease (COPD) patients. Second, the effect of magnesium/aluminium hydroxide on the relative bioavailability of nizatidine, famotidine, cimetidine and ranitidine was evaluated in healthy volunteers. Finally, the effects of nizatidine and omeprazole on the dispositional kinetics of phenytoin were evaluated in healthy volunteers. Only cimetidine altered the steady-state kinetics of oral theophylline, slowing theophylline clearance by 25%. Each of the H2-receptor antagonists exhibited a modest decline in relative bioavailability when ingested with antacid. Antacid ingestion decreased the bioavailability of famotidine, ranitidine and cimetidine by 20-25%, and the bioavailability of nizatidine by 12%. Each of these effects was statistically significant. Finally, it was found that neither omeprazole nor nizatidine affected the single dose kinetics of phenytoin.

Adolescent↗
PubMed1993

Effects of PEG-electrolyte (Colyte) lavage on serum acetaminophen concentrations. A model for treatment of acetaminophen overdose.

The purpose of this study was to evaluate whole gut lavage with polyethylene glycol electrolyte solution (Colyte), as a potentially adjunctive measure in lowering serum acetaminophen levels. The effect of bowel lavage was evaluated on serial serum acetaminophen concentrations after 2-g and 4-g doses in 7 and 12 male patients, respectively. Mean peak level of serum acetaminophen after 2 g (60 min after intake) was not significantly lowered by bowel lavage. After 4 g, peak acetaminophen serum levels were significantly lower after bowel lavage (65.4% of controls, P < 0.001). Urinary concentrations of the mercapturic acid conjugate of the toxic metabolite were also significantly reduced by lavage (55% after 2 g and 45% after 4 g, P < 0.01). Activated charcoal given orally after administration of 4 g of acetaminophen had no significant effect on peak serum levels and had no additive effect on lavage. These studies suggest that rapid, complete bowel lavage with a polyethylene glycol electrolyte solution may be beneficial as an adjunct to the treatment of the acetaminophen intoxication.

Acetaminophen↗
PubMed1993

Gaia: goddess and idea.

This paper introduces Gaia theory to the general reader. It provides the necessary background to follow the development of James Lovelock's thinking as he originated the Gaia theory by comparison of the atmospheres around Mars and other planets during his sojourn at NASA. Lynn Margulis' contributions to Gaia are also presented and the bases for her collaboration with Lovelock explored. In addition to descriptions of the discoveries stimulated by Gaia thinking, the paper indicates how Gaians have dealt with the controversies that have arisen over the theory. Finally, the paper touches on the broader aspects of the Gaia idea. Namely, its development into a spiritual elixir, and how it has been a launching platform for interdisciplinary thinking inside of and beyond the boundaries of the sciences.

Animals↗
PubMed1993

Extracorporeal shock wave lithotripsy for calcified ureteral stent.

Calcification of a ureteral stent has been an unusual complication of long-term stent use for bypassing ureteral obstruction or after surgical repair. Open or percutaneous procedures have usually been required to remove the calcification before the stent can be extracted. We report six cases of calcified ureteral stents successfully managed by extracorporeal shock wave lithotripsy (SWL) followed by cystoscopic extraction, thus avoiding open or percutaneous procedures.

Adult↗
PubMed1993

Absence of an inhibitory effect of omeprazole and nizatidine on phenytoin disposition, a marker of CYP2C activity.

The effects of omeprazole (40 mg orally per day) and nizatidine (300 mg orally per day) on the disposition of phenytoin (4.5 mg kg(-1) p.o. single dose) were studied in 18 healthy, young adult males. Total and unbound plasma concentrations of phenytoin were measured for 48 h after each dose of phenytoin. Neither treatment altered the disposition kinetics of phenytoin, the hydroxylation of which is mediated specifically by cytochromes P450 of the 2C subfamily.

Adult↗
PubMed1993

The Hamilton (McMaster) psychiatric network: the evolution of an integrated network of psychiatric services.

For 25 years, the Hamilton-Wentworth region has had a well integrated network of psychiatric services. The initial impetus for its establishment came from the founders of the Department of Psychiatry at McMaster University in 1967. They envisaged a regional network of services that integrated the resources of a community-focused university department with those of local community agencies and other mental health care professionals. Over the years, the evolution of the network has been shaped by changes in the size and composition of the faculty, the emergence of additional clinical services and community programs, new directions in the field of psychiatry and changing economic forces and social values.

Community Mental Health Services↗
PubMed1993

Altered eicosanoid levels in human colon cancer.

Eicosanoids may participate in colon carcinogenesis, as evidenced from work in animal tumor models showing prevention of colon cancer by inhibitors of their synthesis and epidemiologic studies demonstrating reduced risk of colon cancer in long-term users of aspirin and other nonsteroidal antiinflammatory drugs (NSAIDs). The levels of prostaglandin E2 (PGE2), PGF2 alpha, PGI2, thromboxane A2 (TXA2), and leukotriene B4 (LTB4), which represent the cyclooxygenase and 5-lipoxygenase pathways, were determined in 21 pairs of surgically excised human colon cancer and histologically normal mucosa samples 5 to 10 cm away from the tumor. The levels of PGE2 were elevated in colon cancer samples as compared with histologically normal mucosa samples distant from the cancer (p < 0.01), whereas levels of prostacyclin (PGI2) were decreased (p < 0.05). The differences in the levels of PGF2 alpha, TXA2, and LTB4 between normal and malignant tissue were not statistically significant. No statistically significant association was found between the level of each of the eicosanoids assayed and Dukes' stage of colon cancer. These findings, confirming and extending earlier work from tumors and cell culture, suggest that the protective effect of aspirin and other NSAIDs in the development of human colon cancer may be mediated, at least in part, through their inhibition of arachidonic acid metabolism by cyclooxygenase.

Adult↗
PubMed1992

Preparation of immunoaffinity mini-columns for the analysis of platelet activating factor (PAF) in biological samples.

Using an antibody to BN 52719, an analogue of platelet activating factor (PAF), immunoaffinity mini-columns for the separation of PAF from biological samples were prepared. Rabbits were immunized with BN 52719 and immunoglobulin G (IgG) from the antiserum was coupled with Sepharose 4B. The resulting suspension of the IgG-coated Sepharose 4B in 25 mM phosphate buffer (pH 6.9) was poured into a plastic mini-column (bed volume 2.0 x 0.8 cm). Stepwise elution of the column with methanol revealed that lyso-PAF is eluted with 20-30% methanol in water whereas PAF is eluted with 50-80% methanol. For the determination of PAF in biological samples, it is recommended that lipids are extracted from the samples and the extract, reconstituted in 20% methanol, is loaded on the column. The column is then washed with 50% methanol followed by elution of PAF with 80% methanol. A small amount of [3H]PAF is added to the samples for measurement of the recoveries of PAF during the procedures of extraction and elution. The PAF is then quantified by radioimmunoassay or bioassay. Employing the immunoaffinity mini-column and radioimmunoassay, the contents of PAF in macrophages and conditioned medium after stimulation with calcium ionophore A23187, or tumor promoters such as TPA and thapsigargin, were measured.

Animals↗
PubMed1992

Comparative investigation of the influence of nizatidine, ranitidine, and cimetidine on the steady-state pharmacokinetics of theophylline in COPD patients.

The influence of usual regimens of the H2 blocking drugs, cimetidine, ranitidine, and nizatidine on the steady-state plasma concentrations and pharmacokinetic characteristics of theophylline was studied in seventeen patients with chronic obstructive pulmonary disease (COPD). Patients were dosed to steady-state with an oral, sustained-release formulation of theophylline given in therapeutic doses twice daily for 2 weeks. Over the next 4 weeks, each patient received a week-long regimen of each H2 blocker concomitantly with theophylline, and a week-long regimen of theophylline alone (control). At the end of each of the latter 4 weeks the steady-state pharmacokinetics of theophylline were assessed. Neither ranitidine nor nizatidine treatment altered the steady-state pharmacokinetics of theophylline relative to the control phase (i.e. no H2 blocker treatment). Values for theophylline C(ave), Cssmax, AUC0-12, and CLoral were significantly different during cimetidine treatment compared with all other treatments (ranitidine, nizatidine, and control). Cimetidine increased theophylline Cssmax, AUC0-12 and Cave by approximately 32%, and decreased theophylline oral clearance by approximately 23%. The authors conclude that cimetidine alters the steady-state pharmacokinetics of theophylline in COPD patients, whereas ranitidine and nizatidine are without effect.

Administration, Oral↗
PubMed1992

Antibodies to brevetoxin B: serologic differentiation of brevetoxin B and brevetoxin A.

A brevetoxin B immunogen was prepared by reacting brevetoxin B with the amino groups of bovine albumin followed by treatment with sodium borohydride. Immunized rabbits produced antibodies that bound [3H]brevetoxin B-alcohol. This binding increased with repeated immunization (KD for one rabbit after three courses of immunization was about 10 pM). Brevetoxin B inhibited greater than 500 times more effectively than brevetoxin A. When tested in a competitive binding assay with [3H]brevetoxin B-alcohol-brevetoxin B antibody, the alcohol was six times more effective as an inhibitor than brevetoxin B. Despite some similarities in structure with brevetoxin A, the antibodies to brevetoxin B did not recognize the backbone of brevetoxin A.

Animals↗
PubMed1991

Regulation of arachidonic acid metabolism by phenylarsine oxide.

Preincubation of rat liver cells (the C-9 cell line) for 25 min with phenylarsine oxide at levels ranging from 0.06 to 0.6 microM amplifies prostaglandin I2 production when subsequently stimulated by platelet activating factor, lysine vasopressin, bradykinin, thapsigargin, and the Ca2+ ionophore, A-23187, but not that stimulated by exogenous arachidonic acid. The amplification is decreased after preincubation for 25 min with 1.8 microM phenylarsine oxide. Preincubation of mouse lymphoma cells (the WEHI-3 cell line) with phenylarsine oxide at levels ranging from 0.06 to 1.8 microM for 60 min does not affect prostaglandin E2 levels but inhibits leukotriene B4 and C4 production stimulated by the Ca(2+)-ionophore, A-23187. Amplification of prostaglandin production by phenylarsine oxide is reversed 100 times more effectively by 2,3-dimercaptopropanol than by 2-mercaptoethanol. Deesterification of lipids appears to be regulated positively in rat liver cells and leukotriene production negatively in mouse lymphoma cells by phosphorylation of tyrosine.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Binding competition of okadaic acid derivatives to anti-okadaic acid antibody.

The serologic activities of structurally related okadaic acid derivatives have been determined. Binding of [3H]okadaic acid to rabbit anti-okadaic acid is inhibited with equal effectiveness by okadaic acid, dinophysistoxin-1, acanthifolicin, okadaic acid tetramethyl ether, and okadaic acid spiroketal II. Okadaic acid spiroketal I, which lacks the F- and G-rings of okadaic acid, inhibits serologic binding about 60 times less effectively. The F- and G-rings of okadaic acid may comprise part of the epitopes recognized by some of the polyclonal antibodies.

Animals↗
PubMed1991

Effects of okadaic acid on agonist-stimulated PGI2 production by rat liver cells (the C-9 cell line).

Preincubation of rat liver cells (the C-9 cell line) with okadaic acid (0.6 microM), a known inhibitor of protein-serine/threonine phosphate phosphatases 2A and 1, for 30 min amplified 6-keto-PGF1 alpha production stimulated by thapsigargin, thrombin, platelet activating factor (PAF), 12-O-tetradecanoylphorbol-13-acetate (TPA), the Ca2+ ionophore A-23187 and lysine-vasopressin (Lys.ADH) but not that stimulated by exogenous arachidonic acid. The amplification occurred within minutes after addition of the stimulators. The effect of preincubation was time dependent. Preincubation of the cells with okadaic acid (0.6 microM) for longer than 30 min decreased this amplification. The results suggest that inhibition of protein-serine/threonine phosphate phosphatase(s) can both positively and negatively regulate deesterification of phospholipids although the negative regulation may reflect a toxic response. Microcystin LR and nodularin, inhibitors of protein-serine/threonine phosphate phosphatases 2A and 1 in vitro, did not amplify 6-keto-PGF1 alpha production by PAF when incubated with intact cells.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Amplification of prostaglandin I2 production by thapsigargin.

Rat liver cells (the C-9 cell line) are synergistically stimulated to produce prostaglandin I2 (PGI2) when incubated in the presence of thapsigargin and several recombinant human growth factors or tumor promoters, including basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-alpha (TGF-alpha), 12-O-tetradecanoylphorbol-13-acetate (TPA), teleocidin and aplysiatoxin, but not acidic fibroblast growth factor (aFGF). The production of PGI2 by exogenous arachidonic acid in the presence of thapsigargin is not amplified. The effects of varying levels of bFGF on PGI2 production in the presence of thapsigargin are biphasic: at low levels (0.05 nM) bFGF's effect is synergistic; at high levels (24 nM) it is not.

Animals↗
PubMed1991

Actions of vanadate on arachidonic acid metabolism by cells in culture.

Sodium vanadate (11 microM) amplified the PGI2 production of rat liver cells (the C-9 cell line) incubated with thrombin, platelet activating factor, lysine-vasopressin, the Ca2(+)-ionophore A-23187, interleukin-1 beta, 12-tetradecanoylphorbol-13-acetate, teleocidin, epidermal growth factor, palytoxin, thapsigargin and colchicine but not that stimulated by exogenous arachidonic acid. Sodium vanadate (2.2 microM) also amplified PGF2 alpha production of dog kidney cells (the MDCK cell line) incubated with norepinephrine and, at 0.4 microM, PGI2 production of bovine aorta smooth muscle cells stimulated by serotonin. Sodium vanadate (55 microM) did not affect production of PGE2 and PGF2 alpha in rat basophil leukemia cells (the RBL-1 cell line) stimulated by the Ca2(+)-ionophore A-23187, but did inhibit synthesis of peptide-containing leukotrienes and 12-hydroxyeicosatetraenoic acid. When used with cultured cells at micromolar concentrations, vanadate is known to inhibit protein tyrosine-phosphate phosphatases. These results suggest that in some cells deesterification of lipids is positively regulated, at least in part, by phosphorylation of tyrosine whereas in leukocytes, lipoxygenase activities are negatively regulated, at least in part, by phosphorylation of tyrosine.

6-Ketoprostaglandin F1 alpha↗