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Biomedical subjects

R Vetter

Publications and source records attributed to R Vetter.

At least 55 records · Page 3Linked to original sources

Occupational physical activity, socioeconomic status, and risks of 15 cancer sites in Turkey.

A multiple-site case-control study of 15 cancers (stomach; colon; rectum; larynx; lung; melanoma; skin; female breast; male breast; cervix; ovary; uterus; prostate; testis; and bladder) was conducted to evaluate their association with occupational physical activity and socioeconomic status (SES). A hospital-based study population (3,486 male cases and 379 female cases, and 2,127 male and 244 female controls) was established in an oncological treatment center in Istanbul, Turkey, from 1979-84. Assessment of physical activity and SES was based on job titles held by the study subjects. Two measures of physical activity were developed based on energy expenditure and 'sitting time' during working hours. Observed risks were adjusted for age, smoking, and SES. Elevated risks were observed among workers who held sedentary jobs for cancers of the colon (odds ratio [OR] = 1.6), rectum (OR = 1.3), melanoma (OR = 1.9), male breast (OR = 1.4), prostate (OR = 5.0), and ovary (OR = 2.0). Cancers of the cervix and uterus showed significantly decreasing risks with decreased activity. Risks of cancers of the colon, rectum, larynx, ovary, and melanoma were enhanced after risks for physical activity indices were adjusted for SES, while the associations between physical activity and cancers of the prostate, cervix, and uterus were weakened after SES adjustment. Risks of melanoma rose significantly with both activity indices after SES adjustment.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Rational protein engineering and industrial application: structure prediction by homology and rational design of protein-variants with improved 'washing performance'--the alkaline protease from Bacillus alcalophilus.

The successful attempt is presented to engineer an enzyme with respect to its technical application by the use of computer-aided protein design techniques. Based on a modeled 3-D structure a number of mutants of a subtilisin-like protease was designed with the aim to increase its washing performance. The model of the highly alkaline subtilisin protease OPTICLEAN from Bacillus alcalophilus was developed by the process of 'modeling by homology' starting with the structure of subtilisin Carlsberg 1CSE.BRK from the Brookhaven protein databank. Amino acid changes and deletions were performed with the graphic protein design program BRAGI. Force field calculations and molecular dynamic simulations were made with AMBER 3.0. The comparison of the model and the later solved X-ray structure of OPTICLEAN shows a high similarity between the two structures. On the other hand, interesting deviations between the two structures were observed in some external loop regions. The comparison shows that the deviations are due to difficulties in the prediction of correct main chain torsion angles of additional prolines and the selection of correct loops in deletion or insertion regions.

Amino Acid Sequence↗

Adult meningitis. Rapid identification for prompt treatment.

To be effective, treatment of meningitis should be based on the history and physical examination, careful examination of the cerebrospinal fluid, and good clinical judgment regarding the most likely pathogen. Meningitis in adults is usually caused by certain common viruses and bacteria, although atypical pathogens should be considered in immunocompromised patients. Supportive therapy measures are appropriate for viral disease, and intravenous acyclovir (Zovirax) may be given if infection with herpes simplex virus is suspected. In cases of presumed bacterial meningitis, antimicrobial agents should be selected that penetrate the blood-brain barrier and maintain activity against the most likely pathogens; antibiotic therapy should be instituted right away, along with supportive measures. Although corticosteroids have proven benefits in the treatment of pediatric populations with Haemophilus influenzae meningitis, their effectiveness in adults has not yet been established. Prophylaxis with vaccines or rifampin is sometimes useful.

Adolescent↗

Physical activity and occupational risk of colon cancer in Shanghai, China.

Using occupational data for over 2000 colon cancer cases diagnosed between 1980 and 1984 in Shanghai, and employment information from the 1982 census for the Shanghai population, standardized incidence ratios (SIR) were computed for occupational groups classified by job types and physical activity levels. Men employed in occupations with low physical activity levels had modest but significantly elevated risks of colon cancer. SIR for jobs with low activity based on sitting time was 121 (95% confidence interval, Cl: 108-135) and based on energy expenditure was 126 (95% Cl: 115-138). Corresponding SIR for women were 99 (95% Cl: 83-118) and 113 (95% Cl: 100-127). The data were also used to screen for specific occupations with elevated SIR to generate leads to occupational colon cancer. Increased incidence was observed for professional and other white collar workers, and male chemical processors and female textile workers. The findings add to the emerging evidence that workplace activity may influence the risk of this common cancer.

China↗

Occupational physical activity and colon cancer risk in Turkey.

A case-control study of 107 colon cancer cases and 486 controls from an oncological clinic in Istanbul was conducted to examine the association between occupational physical activity and colon cancer in Turkey, where incidence of this disease is low. Only two of the four activity measures showed evidence of an increased colon cancer risk for sedentary jobs (time spent sitting OR = 1.5 and occupational energy expenditure OR = 1.6); neither was statistically significant. Subjects below age 55 showed higher risk associated with sedentary jobs than did the older age group, probably due to their adoption of a more western lifestyle, including dietary habits, less activity, and other factors that may interact to increase the risk of colon cancer.

Adolescent↗

Thyroid control of contractile function and calcium handling in neonatal rat heart.

Newborn rats were rendered hyperthyroid (daily subcutaneous injections of L-triiodothyronine, 10 micrograms 100 g-1 body weight) or hypothyroid (0.05% 6-n-propyl-2-thiouracil in drinking water to nursing mothers) during the first 3 weeks of postnatal life. Compared with the euthyroid group, hyperthyroidism resulted in: (1) cardiac enlargement with right ventricular preponderance, (2) increased cardiac contractile function, (3) increased Ca2+ uptake by the sarcoplasmic reticulum (SR), (4) decreased sensitivity to the negative inotropic effect of verapamil and (5) greater inhibition of contractile function by ryanodine. Hypothyroidism generally resulted in opposite changes. The data suggest that the development of the heart and its contractile function during early postnatal life depends on the plasma level of thyroid hormones. In particular, the relative contribution of the SR and sarcolemmal Ca2+ transport to the control of cardiac contractility seems to be markedly affected by altered thyroid states. The postnatal maturation of the SR function is accelerated in hyperthyroidism but retarded in hypothyroidism. Consequently, hyperthyroid hearts appear to be less dependent and hypothyroid ones more dependent on trans-sarcolemmal Ca2+ fluxes when compared with age-matched euthyroid animals.

Animals↗

Mortality among laboratory workers employed at the U.S. Department of Agriculture.

We evaluated the mortality of 835 white male and 36 female laboratory workers employed by the U.S. Department of Agriculture who died between January 1, 1970, and December 31, 1979. For males, the mortality odds ratio for all cancers was 1.0 (95% confidence interval = 0.8-1.2). Colon cancer, lymphosarcoma and reticulosarcoma, nonmalignant diseases of the blood and blood-forming organs, and suicide showed elevated mortality odds ratios. Only colon cancer showed an association with duration of employment as a laboratory worker. In an accompanying case-control study, the risk of colon cancer rose to 3.2 among those who had 20 or more years of employment as a laboratory worker. Among females, breast cancer was elevated (mortality odds ratio = 5.3; 95% confidence interval = 2.8-10.1).

Female↗

A rapid procedure for the purification of cardiac 1,4-dihydropyridine receptors from porcine heart.

Highly purified porcine cardiac sarcolemma was used as a source for purification of mammalian cardiac 1,4-dihydropyridine receptors associated with the voltage-dependent Ca2+ channel. The cardiac digitonin-solubilized receptor prelabeled with (+)-[3H]PN 200-110 was enriched at least 236-fold using an improved, rapid three-step purification protocol which could be completed within 12 h. The purity of the preparation was at least 22%, the yield of the receptors 24%. Photoaffinity labeling experiments with (-)-[3H]azidopine allowed the identification of the cardiac alpha 1 subunit. In contrast to the purified rabbit or guinea-pig skeletal muscle Ca2+ channel complex, none of the purified polypeptides underwent rapid and substantial phosphorylation by the catalytic subunit of the cyclic AMP-dependent protein kinase in vitro.

Affinity Labels↗

Role of sulfhydryl groups in phospholipid methylation reactions of cardiac sarcolemma.

The effect of reagents that modify sulfur-containing amino acid residues in the phosphatidylethanolamine N-methyltransferase was studied in the isolated rat cardiac sarcolemma by employing S-adenosyl-L-[methyl-3H]methionine as a methyl donor. Dithiothreitol protected the sulfhydryl groups in the membrane and caused a concentration- and time-dependent increase of phospholipid N-methylation at three different catalytic sites. This stimulation was highest (9-fold) in the presence of 1 mM MgCl2 and 0.1 microM S-adenosyl-L-[methyl-3H]methionine at pH 8.0 (catalytic site I), and was associated with an enhancement of Vmax without changes in Km for the methyl donor. Thiol glutathione was less stimulatory than dithiothreitol; glutathione disulfide inhibited the phosphatidylethanolamine N-methylation by 50%. The alkylating reagents, N-ethylmaleimide and methylmethanethiosulfonate, inhibited the N-methylation with IC50 of 6.9 and 14.1 microM, respectively; this inhibition was prevented by 1 mM dithiothreitol. These results indicate a critical role of sulfhydryl groups for the activity of the cardiac sarcolemmal phosphatidylethanolamine N-methyltransferase and suggest that this enzyme system in cardiac sarcolemma may be controlled by the glutathione/glutathione disulfide redox state in the cell.

Animals↗

Thyroid control over membrane processes in rat heart.

We have studied the effects of hypo- and hyperthyroidism on sarcolemmal (SL) and sarcoplasmic reticular (SR) ion transport processes and mitochondrial energy production in rat heart. The following conclusions were derived. 1) Compared with euthyroid state, hyperthyroidism led to increased SR Ca(2+)-accumulation. In SL, the activities of Ca(2+)-stimulated adenosine triphosphatase (ATPase), ATP-dependent Ca2+ pumping, and Na(+)-Ca2+ exchanger were not affected; but ouabain-sensitive Na(+)-K(+)-ATPase activity was enhanced. 2) Hypothyroidism resulted in depressed activities of Ca2+ pumps both in SL and SR. In SL, the Na(+)-K(+)-ATPase activity was decreased, but Na(+)-Ca2+ exchange was unaltered. 3) Thus slower relaxation of the hypothyroid myocardium may be attributed to depressed functioning of Ca2+ pumps in SR and SL, whereas faster relaxation of the hyperthyroid heart may be based on increased Ca(2+)-pumping activity of SR. 4) Hyperthyroidism and hypothyroidism, respectively, led to enhanced and decreased rates of mitochondrial phosphocreatine synthesis. The thyroid state appears to control the functional coupling between mitochondrial creatine kinase and ATP-ADP translocase: the energy of oxidative phosphorylation was transformed into phosphocreatine more effectively in mitochondria from hypothyroid hearts than in those from hyperthyroid hearts.

Adenosine Triphosphatases↗

[Obstructive uropathies in early childhood--surgical intervention as renal protection].

Anomalies in the urinary tract can be noticed early by prenatal sonography. In the case of obstruction, a decompressive procedure can follow immediately after birth. Long-term results of renal function in cases of pyeloureteral obstructions after 6-10 years make it clear that results are better the earlier pyelon resection is performed. In cases of obstructive megaureter, operative procedures are indicated for severe disturbances of ureteral transport. Progressive renal and ureteral wall destruction is promoted by performing operations too late.

Child, Preschool↗

Alteration of lipid methylation by oleic acid in rat heart sarcolemma.

Incubation of rat heart sarcolemma with the methyl donor S-adenosyl-L-[methyl-3H] methionine resulted in N-methylation of phosphatidylethanolamine and methylation of a heterogenous fraction of nonpolar lipids in the membrane. Oleic acid reduced the synthesis of N-methylated phospholipids and stimulated the methyl group incorporation into nonpolar lipids in a concentration-dependent manner. Both methylation reactions were not affected when oleic acid was substituted by methyl ester of oleic acid or by the detergents sodium deoxycholate or Triton X-100. This study suggests that the enzymatic biosynthesis of the N-methylated phospholipids may be altered by free fatty acids.

Animals↗

[Hamartoma of the liver in childhood].

Liver hamartoma is one of the very rare findings in childhood. It is a dysontogenetic malformation that grows clinically manifest with tumour-like appearance in the first or second year of age. Cystic and solid formations are described in this report. Findings are usually clearly delimited from clinically intact liver parenchyma. In surgical extirpation, that delimitation should be stringently observed to avoid unnecessary blood loss. The prognosis generally is good and should not be jeopardised by delay of surgical therapy. Reported are two cases of liver hamartoma, with both patients being laparotomised at the age of one and a half years.

Hamartoma↗

Sarcolemmal Na+-Ca2+ exchange and sarcoplasmic reticulum Ca2+ uptake in several cardiac preparations.

Calcium transport mediated by the sarcolemma (SL) Na+-Ca2+ exchanger and by the sarcoplasmic reticulum (SR) Ca2+ pump were studied in crude membranes from ventricular tissue of newborn and young rat, adult frog, guinea pig, chick, hamster, Rhesus monkey, rabbit, and pig. Transport activities were evaluated per mass of membrane protein and heart tissue. Relative to unit of ventricular mass Na+-Ca2+ exchange activity (at [Ca2+] = 75 microM) is highest in newborn rat, frog, guinea pig, and chick amounting to about 17.7, 17.5, 16.2, and 10.1 mumol Ca2+/kg wet weight/2s, respectively. Considerable lower values were obtained in the other species. The lowest Na+-Ca2+ exchange rate was found in 40-day old rat amounting to 2.4 mumol Ca2+/kg wet weight/2s. Parallel determination of active SR Ca2+ uptake in the same membrane preparations reveals that the quantitative relationship between the two different Ca transport processes is not invariant with respect to species and stage of differentiation. The data suggest that Ca2+ handling in small-sized cardiac cells with poorly developed SR (newborn rat, frog) depends to a greater extent on Ca2+ fluxes via the SL Na+-Ca2+ exchanger as compared to differentiated cardiac cells of adult mammalian and avian species. By contrast, the contribution of SR Ca2+ transport to cardiac Ca2+ movements becomes more predominant in differentiated cardiac cells.

Animals↗

Characterization of calcium antagonist receptors in highly purified porcine cardiac sarcolemma.

Drug receptors for the Ca-antagonists nitrendipine and (-)desmethoxyverapamil (D-888) were studied in porcine cardiac sarcolemma. The dihydropyridine (DHP) derivative [3H]nitrendipine binds to a single population of high affinity sites (KD = 0.44 +/- 0.10 nM, Bmax = 2.43 +/- 0.19 pmol/mg; (n = 8), whereas the phenylalkylamine derivative [3H](-)D-888 interacts with high and low affinity sites of KD = 5.1 +/- 1.4 nM and KD = 438 +/- 86 nM (n = 6) in the same membrane preparations. The antagonists tested differ also with respect to their pharmacological efficacy on cultured intact heart myocytes. The EC50 value of the negative chronotropic effect exerted by D-888 corresponds to its high affinity binding component. Nitrendipine exhibit a 200-fold lower pharmacological efficacy, as would be expected from binding data.

Animals↗

Fast activation of Ca2+-ATPases in plasma membranes from cardiac muscle and from ascites carcinoma cells: a possible function of endogenous calmodulin.

Content of endogenous calmodulin, binding of calmodulin to, and Ca2+-ATPase activity in plasma membranes of cardiac muscle. Ehrlich ascites carcinoma (EAC) cells and erythrocytes were examined. The content of endogenous calmodulin in cardiac and EAC cells was shown to be considerably higher than in erythrocyte membranes. Ca2+-independent binding of calmodulin to cardiac and EAC cell membranes was found to be realized by some low molecular weight proteins. Ca2+-ATPases in cardiac and EAC cell membranes differ from those in erythrocytes with respect to their activation by Ca2+ and calmodulin. The erythrocyte enzyme is strongly stimulated by exogenous calmodulin and reaches its maximum activity about 2 min after Ca2+-addition. In contrast, the Ca2+-ATPases in cardiac and EAC cell plasma membranes cannot be considerably stimulated by exogenous calmodulin and are instantaneously activated by Ca2+.

Animals↗

Sarcolemmal Na-Ca exchange and sarcoplasmic reticulum calcium uptake in developing chick heart.

Ontogenetic changes in calcium transport mediated by the sarcolemmal Na-Ca exchanger and by the sarcoplasmic reticulum calcium pump were studied in crude membranes from chick heart. Transport activities were evaluated per mass of membrane protein and heart tissue. Relative to unit heart mass Na-Ca exchange activity increases linearly from embryonic day 4 to day 10 of newborn stage. The overall increase is about 20-fold. An excellent correlation exists between activity of sodium gradient-induced calcium uptake and ouabain-sensitive (Na,K)-ATPase in crude membranes of embryonic, newborn and adult hearts. In the same membrane preparations active calcium uptake into vesicles of sarcoplasmic reticulum increases about 3-fold from embryonic day 4 to embryonic day 7, and then increases continuously until day 20. This is followed by a 3-fold elevation in reticular calcium accumulation at hatching on day 21. Maximal sarcoplasmic reticulum calcium transport activity reached at day 10 after hatching is 40- to 50-fold greater than activity values at embryonic day 4. In adult hearts the activities of both Na-Ca exchange and reticular calcium uptake drop to levels characteristic for the late embryonic period. This comparative study of sarcolemmal sodium gradient-dependent calcium flux and reticular calcium sequestration demonstrates that during chick heart differentiation the two calcium transport systems do not develop in parallel. Na-Ca exchange appears to play a greater role in calcium control of embryonic as compared to newborn and adult hearts. By contrast, the contribution of sarcoplasmic reticulum calcium transport to cardiac calcium movements becomes more predominant during and after hatching.

Animals↗

Putative Ca2+ channels in cardiac membranes. Subcellular distribution of [3H]nitrendipine receptors.

The binding of Ca2+ channel blocking drug nitrendipine was studied in purified sarcolemma (SL), fragmented sarcoplasmic reticulum (SR), and crude membranes isolated from porcine left ventricle. The density of specific [3H]nitrendipine binding sites was compared to Na+/Ca2+ exchange and (Na+, K+)ATPase activities of each membrane preparation. Enrichment of [3H]nitrendipine binding sites in purified SL correlates excellently with the purification of the two studied sarcolemmal marker activities. The results suggest that high affinity nitrendipine receptors are solely localized in cardiac SL.

Animals↗