Biomedical subjects

G Levin

Publications and source records attributed to G Levin.

At least 37 records · Page 2Linked to original sources

PubMed1995

Regulation of RCK1 currents with a cAMP analog via enhanced protein synthesis and direct channel phosphorylation.

We have recently shown that the rat brain Kv1.1 (RCK1) voltage-gated K+ channel is partially phosphorylated in its basal state in Xenopus oocytes and can be further phosphorylated upon treatment for a short time with a cAMP analog (Ivanina, T., Perts, T., Thornhill, W. B., Levin, G., Dascal, N., and Lotan, I. (1994) Biochemistry 33, 8786-8792). In this study, we show, by two-electrode voltage clamp analysis, that whereas treatments for a short time with various cAMP analogs do not affect the channel function, prolonged treatment with 8-bromoadenosine 3',5'-cyclic monophosphorothioate ((Sp)-8-Br-cAMPS), a membrane-permeant cAMP analog, enhances the current amplitude. It also enhances the current amplitude through a mutant channel that cannot be phosphorylated by protein kinase A activation. The enhancement is inhibited in the presence of (Rp)-8-Br-cAMPS, a membrane-permeant protein kinase A inhibitor. Concomitant SDS-polyacrylamide gel electrophoresis analysis reveals that this treatment not only brings about phosphorylation of the wild-type channel, but also increases the amounts of both wild-type and mutant channel proteins; the latter effect can be inhibited by cycloheximide, a protein synthesis inhibitor. In the presence of cycloheximide, the (Sp)-8-Br-cAMPS treatment enhances only the wild-type current amplitudes and induces accumulation of wild-type channels in the plasma membrane of the oocyte. In summary, prolonged treatment with (Sp)-8-Br-cAMPS regulates RCK1 function via two pathways, a pathway leading to enhanced channel synthesis and a pathway involving channel phosphorylation that directs channels to the plasma membrane.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1995

Incorporation of all-trans- or 9-cis-beta-carotene into mixed micelles in vitro.

Various studies suggest that all-trans- and 9-cis-beta-carotene are absorbed in the intestine to different extents. The present study was undertaken to evaluate the degree of in vitro incorporation of the two isomers into intestinal mixed micelles, which is an essential early step in the absorption process. The micelles were designed to simulate those present during fat digestion in the lumen of the human small intestine with respect to bile salts, lipids, pH and temperature. Solutions of all-trans- and 9-cis-beta-carotene at various ratios were added to the lipid mixture. A direct correlation was seen between the 9-cis-beta-carotene level in the mixture and the degree of total beta-carotene incorporation into micelles. An increased level of all-trans-beta-carotene in the system led to a decrease in the percentage of beta-carotene incorporated into the micelles. In contrast, when carotene mixtures enriched with the 9-cis isomer were used, an increase in the level of total carotene in the solution was accompanied by a constant or even enhanced carotene incorporation. The results indicate that the differences in the absorption of beta-carotene isomers might be the result of their different ability to be incorporated into the lipid micelles of the intestinal lumen. In addition, the results point toward the possibility that ingestion of 9-cis-beta-carotene by humans may increase carotene availability.

Bile Acids and Salts↗

PubMed1995

A cancer-prevention intervention for disadvantaged women: design and implementation.

A cancer-prevention mini-course was designed to increase knowledge about breast and cervical cancers as well as to improve attitudes and behaviors regarding preventive health care among minority and medically underserved women. The culturally-sensitive two-hour psycho-educational intervention was developed as an interactive curriculum in English- and Spanish-language versions for home health care attendants. After development and piloting, the course was offered as part of the weekly 40-hour training program for home attendants in Bronx, New York. After six months it was offered as in-service training for home attendants employed by a licensed home attendant-training agency. The home attendants who participated in the mini-course were primarily Hispanic (62%) and black (31%). Results of evaluation indicate that the mini-course has been remarkably successful in achieving its goals. Primary measures of its success include: 1) integration of the mini-course into the settings in which it is being offered; 2) student participation, absorption of material, and enthusiasm for the course. The mini-course has been successfully incorporated into the training agencies, with strong staff commitment to the program. Participants evince high levels of enthusiasm for the class, reporting that they have learned new information and have especially enjoyed the interactive nature of the class. Though the development of this cancer-prevention mini-course (and its materials) as well as integrating it into appropriate settings required a substantial investment of time and resources, now that it is developed, the intervention proves to be efficient and effective, and is meeting a large need.

Adult↗

PubMed1995

Intrarenal dopamine participation in frusemide diuretic and natriuretic responses to frusemide.

1. Dopamine (DA) involvement in the renal response to frusemide was analysed using the isolated perfused rat kidney preparation. Endogenous DA levels were increased through the infusion of its precursor levodopa (LD) (0.5 or 1 microM) whereas benserazide (50 or 100 microM), an inhibitor of the enzyme L-dopa-decarboxylase, was used to decrease DA synthesis. 2. Frusemide administration (0.3-20 nmols) induced a dose-dependent increase in fractional excretion of water (FE H2O), sodium (FE Na+) and glucose (FEG). FE Na+ elicited by the diuretic was enhanced 30-40% by 0.5 microM of LD (n = 5, P < 0.05), and 60-80% by LD 1 microM (n = 5, P < 0.05). FE H2O produced by the diuretic was enlarged 80-100% by 0.5 microM (n = 5, P = 0.05), and 130-170% by 1 microM of LD (n = 5, P < 0.01). The increase produced by both concentrations of LD on FEG was 200% for the lowest dose of the diuretic (n = 5, P < 0.01), and 90% for the highest (n = 5, P < 0.05). 3. Benserazide (BZ) (100 microM) decreased the F.E. Na+ induced by frusemide (n = 5, P < 0.05) by 32-42%, and completely abolished frusemide effects on FE H2O and FEG (n = 5). 4. In conclusion, our results suggest that endogenous dopamine participates in the frusemide-induced diuresis and sodium excretion within the kidney, and that the participation of extrarenal factors is not essential for this effect. Dopamine may be involved in frusemide-induced inhibition of proximal sodium reabsorption.

Animals↗

PubMed1995

Furosemide renal excretion rate and the effects of the diuretic on different tubular sites are modified by endogenous dopamine in normohydrated rats.

The present study was designed to explore the involvement of endogenous dopamine in furosemide excretion and in the actions of the diuretic on tubular sodium reabsorption. The dose-response relationship for the diuretic effect of furosemide given as i.v. bolus injections (0.2-7.5 mg.kg-1) was studied by clearance technique in pentobarbital-anesthetized rats treated with vehicle, benserazide (BZ) (25 mg.kg-1 i.v.) or SCH 23390 (50 micrograms.kg-1 + 10 micrograms.kg-1.min-1 i.v.). Furosemide induced the maximal diuresis 15 to 30 min after i.v. administration. The diuretic response was dose-dependent and was reduced in the animals treated with BZ and SCH 23390. Fractional sodium excretion was also increased by furosemide from 1.8 to 7.5% during the same period. This effect was reduced by both BZ or SCH 23390 by 35 to 50%. The effects of furosemide on proximal and distal renal tubules were dissected by measuring the renal lithium clearance (CLi+). Furosemide effective on proximal tubular sites (measured by FENa+ prox = CLi+/Cln) were completely abolished by BZ and SCH 23390, whereas both drugs reduced furosemide effects on distal tubular sites (measured by FENa+ distal = CNa+/CLi+) by 20 to 40%. Furosemide excretion rate during the peak response to the diuretic was measured in the urine. BZ and SCH 23390 diminished furosemide excretion by 45 to 80% as compared with vehicle-treated animals. The furosemide tubular effects and the proximal and distal functions measured by CLi+ determined during the peak response were correlated to the maximal excretion rate of furosemide in the urine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Phosphorylation by protein kinase A of RCK1 K+ channels expressed in Xenopus oocytes.

Phosphorylation-mediated regulation of voltage-gated K+ channels has been implicated in numerous electrophysiological studies; however, complementary biochemical studies have so far been hampered by the failure to isolate and characterize any K+ channel proteins of distinct molecular identity. We used the Xenopus oocyte expression system to study the biosynthesis and phosphorylation by protein kinase A (PKA) of rat brain RCK1 (Kv1.1) K+ channel protein. RCK1 protein was isolated by immunoprecipitation from oocytes injected with RCK1 cRNA and analyzed by SDS-polyacrylamide gel electrophoresis (SDS-PAGE). The channel protein was expressed in the form of several polypeptides. The 57-kDa polypeptide, usually the major constituent, resided both in the cytosol and in the plasma membrane. Its levels were correlated with RCK1 current amplitudes (IRCK1) and upon incubation of the cRNA-injected oocytes with tunicamycin, its molecular weight was decreased and at the same time IRCK1 was reduced. These results suggest that the membranal 57-kDa polypeptides represent functional channels that are N-glycosylated. Furthermore, a study of the phosphorylation of the RCK1 polypeptides revealed that the 57-kDa polypeptide was specifically targeted for phosphorylation by PKA. It could be phosphorylated in vitro by the catalytic subunit of PKA (PKA-CS). In its native state in intact oocytes, the 57-kDa polypeptide was partially phosphorylated and could be further phosphorylated in vivo by addition of a membrane-permeant cAMP analog. Site-directed mutagenesis demonstrated that phosphorylation of a single site on the C-terminus of the channel molecule fully accounts for these phosphorylations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Antioxidant activity of 9-cis compared to all-trans beta-carotene in vitro.

In the present in vitro study we compared the antioxidative efficiency of the 9-cis to that of the all-trans beta-carotene. The 9-cis isomer was isolated from the alga Dunaliella bardawil. The experimental system consisted of 80 mM methyl linoleate, 4 mM azo-bis-2,2'-dimethylvaleronitrile (AMVN) as a free radical generating agent, and 200 microM beta-carotene (synthetic all-trans, 9-cis or a mixture of the 9-cis and all-trans isomers, having a ratio of 2.3). During the incubation at 37 degrees C the mixtures were analyzed for methyl linoleate hydroperoxides, total beta-carotene concentration, and its isomeric composition. The content of 9-cis beta-carotene in the various systems was negatively correlated to the level of the hydroperoxides accumulated, and positively related to the residual beta-carotene amount. The HPLC analysis of the system containing both isomers revealed a continuous decrease in the 9-cis to all-trans isomer ratio. The results suggest that the 9-cis beta-carotene has a higher antioxidant potency than that of the all-trans isomer and, therefore, it protects the methyl linoleate, as well as the all-trans isomer, from oxidation. This isomeric difference might be explained by the higher reactivity of cis, compared to trans, bonds.

Antioxidants↗

PubMed1994

Opioid and sympathetic nervous system activity in cluster headache under verapamil or prednisone treatment.

This study was undertaken to evaluate the effect of treatment with prednisone or verapamil on plasma met-enkephalin (ME), neutrophil met-enkephalin containing peptides (NMECP) and free and conjugated plasma catecholamines (CA) in cluster headache (CH) patients. After obtaining a basal sample, patients were randomly selected to be treated with either verapamil (n = 5) or prednisone (n = 5). A second blood sample was obtained 10 days after starting treatment. At this time all patients were free of symptoms. ME (0.49 +/- 0.10 pmol/mL) and NMECP (35.1 +/- 2.4 pmol/mg protein) levels after prednisone treatment were significantly higher (P < 0.05) than in basal conditions (0.29 +/- 0.08 pmol/mL and 27.14 +/- 2.4 pmol/mg protein), while no differences were found in catecholamine levels. No differences in ME, NMECP or CA were found during verapamil treatment. Our results suggest that in CH the two drugs act through different mechanisms. The relief of the bout obtained with prednisone may be related to the opioid system stimulation observed in these patients.

Catecholamines↗

PubMed1994

9-Cis beta-carotene as a precursor of retinol isomers in chicks.

The possibility that 9-cis beta-carotene serves as a precursor for retinol in general, and particularly for 9-cis retinol, was studied in chicks, in which the 9-cis beta-carotene is preferentially accumulated. One week old chicks were fed a synthetic diet supplemented with 9-cis and all-trans beta-carotene mixtures, in which the 9-cis isomer content was 9, 19.1, 31.2, 40.8, 57.7 or 77.0%. It was found that an elevation in the dietary 9-cis beta-carotene level led to a decrease in the hepatic retinol stores, despite the increased level of total and 9-cis beta-carotene in the liver. HPLC chromatography revealed the presence of all-trans, 13-cis and 9-cis retinol in the livers. A high 9-cis beta-carotene diet brought about a significant, but very small, elevation in the part of the cis retinol isomers relative to the all-trans isomer. It was concluded that 9-cis beta-carotene has a low activity as a precursor of retinol in general. This decreased activity is not due to a low availability of the isomer to the enzymatic cleavage. It seems also that 9-cis beta-carotene is not an efficient precursor of 9-cis retinol.

Animals↗

PubMed1993

N-myc oncogene and urinary catecholamines in children with neuroblastoma.

This paper reports the analysis of N-myc amplification, urinary vanillylmandelic acid (VMA), and norepinephrine (NE) excretion and survival in 22 children with neuroblastoma and 7 with ganglio-neuroblastoma. Five patients had N-myc amplification (from 30 to more than 200 copies), all of whom had advanced-stage disease. The urinary excretion of VMA was normal in all of them, only one showed increased NE excretion. All patients with stage C-D disease and one copy of N-myc had increased VMA urinary excretion and increased (9/14) or normal (5/14) NE urinary excretion. All patients with stage A or B disease had one copy of N-myc. Half of them showed increased VMA urinary levels, while only 3/10 showed increased NE urinary values. Comparison of cumulative survival curves in relation to N-myc amplification and to VMA and NE urinary excretion showed a clear parallelism. Amplification of N-myc corresponded to normal VMA and NE urinary excretion, and was associated with the worst prognosis (P < 0.01), while increased VMA and/or NE excretion was found in patients with only one copy of N-myc.

Child↗

PubMed1993

The involvement of sodium ions in the positive inotropic effect of naloxone.

1. The opiate antagonist naloxone induces a positive inotropic effect in isolated cardiac muscles. 2. The response to naloxone is dependent on the presence of Na+ in the bathing solution, is proportional to the rate of electrical stimulation, and increased in the presence of veratridine. 3. Lowering [K+]o to 50% augments the response, while complete removal of K+ from the extracellular solution attenuates the response to naloxone. 4. Maximal concentration of naloxone decreases the inotropic effect of the cardiac glycoside ouabain. 5. The results indicate the involvement of intracellular sodium accumulation in the positive inotropic effect of naloxone, probably through the inhibition of the sarcolemmal Na(+)-K+ pump.

Animals↗

PubMed1993

Involvement of renal dopamine synthesis in the diuretic effect of furosemide in normohydrated rats.

The present study was designed to investigate whether the modification of dopamine synthesis affects furosemide responses. Experiments were performed on pentobarbital-anesthetized rats. Basal urine flow was approximately 3 microliters/min-1/g-1 of kidney weight (k.w.); furosemide (0.2 mg/kg-1 i.v.) induced a rapid diuretic effect (19.3 +/- 1.4 microliters/min-1/g-1 of k.w.). The dopadecarboxilase inhibitor, benserazide (25 mg/kg-1 i.v.), reduced furosemide-induced diuresis to 8.3 +/- 2.1 microliters/min-1/g-1 of k.w., whereas levo-dihydroxyphenylalanine (L-dopa; 1 micrograms/kg-1/min-1 infused for 60 min) increased it to 41.4 +/- 6.1 microliters/min-1/g-1 of k.w. Natriuretic response and fractional Na+ excretion induced by furosemide were significantly lower in benserazide-treated and higher in L-dopa-treated animals. Urine dopamine (DA) excretion was enhanced by furosemide from 0.44 +/- 0.05 to 0.98 +/- 0.22 ng/min-1/g-1 of k.w. and was markedly reduced in benserazide-pretreated animals, whereas both basal DA excretion and that induced by furosemide were increased significantly during L-dopa infusion. However, in benserazide- or L-dopa-treated animals, basal urine flow was not different from the control group. Urine furosemide excretion was reduced by 60% by benserazide treatment and increased by 62% during L-dopa infusion. The results are consistent with the suggestion that although endogenous DA is apparently unimportant in the maintenance of basal urine output, it is involved in furosemide-induced diuresis. The diuretic response can be altered by acute administration of substances that affect dopamine synthesis.

Animals↗

PubMed1992

Food restriction and membrane fluidity.

The fluidity of the erythrocyte membrane derived from growing rats raised under restricted food intake was found to be higher than the fluidity of the respective membranes from ad libitum fed animals. Considering the apparent relationship between the decrease in membrane fluidity and aging, the results point to the possible beneficial effects of food restriction at a young age.

Aging↗

PubMed1992

Habituation to zipeprol hydrochloride during pregnancy.

Zipeprol hydrochloride is a synthetic antitussive agent that has shown little evidence of addictive potential in animal studies. Despite this, several reports of abuse and abuse-related over-dosage have been published. Abuse of this drug has now become a problem in the United States-Mexico border region. We report the specific case of a pregnant woman habituated to zipeprol without evidence of other drug abuse and an abstinence syndrome observed in her newborn infant.

Adult↗

PubMed1990

Effects of exercise on myocardial catecholamine content and ischemic injury in dogs with gradual coronary occlusion.

The effects of exercise on catecholamine content and the extent of myocardial damage in dogs with Ameroid constrictor occlusion of the left circumflex coronary artery were determined. Tissue samples from both the anterior and posterior walls of the left ventricle were obtained for determination of catecholamine content, and the rest of the ventricles were processed for histologic examination. When subjected to treadmill exercise for 40 days after surgery, obstructed animals performed significantly less exercise than sham-operated animals and showed significantly higher percentages of ischemia and necrosis in the left ventricle than sedentary, obstructed, sham-operated, or control dogs. Levels of norepinephrine and epinephrine in the posterior wall of the left ventricle were significantly lower than in the other groups. Our data show that exercise in this well-known model of chronic coronary artery stenosis produced deleterious effects on the myocardium and suggest a marked heterogeneity of catecholamine stores in the myocardium that may have important functional and electrophysiologic consequences.

Animals↗

PubMed1990

Riboflavin deficiency and the function and fluidity of rat erythrocyte membranes.

The effect of riboflavin deficiency on the fluidity and function of the red blood cell (RBC) membrane and on the activity of some enzymes involved in antioxidant defense mechanisms was studied. Growing male rats were fed an experimental (riboflavin-deficient) or a control (riboflavin-supplemented) diet. Following 7 wk of feeding, RBC from riboflavin-deficient rats contained higher levels of peroxidation products, most likely due to decreased glutathione reductase activity. An elevation in glutathione peroxidase activity was also observed whereas the activity of catalase and superoxide dismutase was not affected. Membrane fluidity was studied by fluorescence polarization, using 1,6-diphenyl-1,3,5 hexatriene (DPH) as a probe. The fluidity of RBC membranes isolated from riboflavin-deficient rats was significantly lower than that of the controls. This decreased fluidity was accompanied by an increase in the activity of the membrane-bound enzyme acetylcholinesterase. This study demonstrated that a decrease in cells' ability to cope with peroxidative damage as a result of riboflavin deficiency may lead to changes in the fluidity and function of membranes.

Acetylcholinesterase↗

PubMed1990

Asbestotic radiological abnormalities among United States merchant marine seamen.

There has been limited information concerning the prevalence of radiologically evident parenchymal and pleural fibrosis consistent with prior exposure to asbestos among merchant marine seamen, despite the wide use of asbestos in ship construction until the late 1970s and subsequent exposure of seamen to the asbestos that had been installed. A total of 3324 chest radiographs (1985-7) of long term United States seamen were reviewed. One third (34.8%) had parenchymal or pleural abnormalities, or both (ILO classification); pleural changes were predominant. Abnormalities increased with longer duration from onset of shipboard exposure (as defined by first year at sea). The prevalence of asbestotic changes was greater among seamen who had served in the engine department (391/420; 42.5%) compared with seamen in other departments, including deck (301/820; 36.6%), steward (278/981; 28.4%), or with service in multiple departments (167/541; 30.9%). Since many vessels, particularly those built before 1978, contain asbestos materials, appropriate engineering controls (including complete removal, if possible) are required as well as appropriate medical surveillance for those who served aboard such ships.

Asbestos↗

PubMed1989

Comparison of the reactions of older and younger patients to intensive care.

To determine whether age affected the attitudes of patients to intensive care, we administered a questionnaire to 57 patients who had been hospitalized in our ICU or coronary care unit (CCU). The 28 men and 29 women ranged in age from 20 to 92 yr (mean 58.4). Nineteen patients were greater than or equal to 70 yr and nine were greater than or equal to 80 yr. The "intensity" and "severity" of the treatments were similar in the older and younger patients, both men and women, in the ICU and CCU. The great majority of the patients, both old and young, were satisfied with their treatment and outcome, and expressed willingness to undergo similar treatment(s) in the future, if needed. Only five patients were dissatisfied with their treatment: two were greater than 70 yr, the other three were 27, 62, and 65 yr. We did not interview a large number of patients and thus, cannot draw far-reaching conclusions without additional study. Nevertheless, although we expected that older patients would be particularly distressed about their treatments and hence, say they would decline them in the future, in this study both the older and the younger patients were highly accepting of the treatment they received.

Adult↗