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Biomedical subjects

S Fischer

Publications and source records attributed to S Fischer.

At least 397 records · Page 22Linked to original sources

[Clinical relevance of the determination of TSH-binding inhibitory immunoglobulins (TBII) in patients with immunogenic hyperthyroidism in methimazole therapy].

In 38 patients with immunogenic hyperthyroidism a follow-up was performed to estimate the value of TBII before, during and after methimazole therapy. Before therapy increased TBII were detectable in 37 patients (94.4%). After 12 months methimazole therapy 25 patients had TSH-receptor antibodies (66%) within the normal range. In 13 patients positive antibody titres were found. In most cases persistence of increased TBII-values during drug treatment was an indicator of the persistence of active hyperthyroidism (10 of 13 patients). In the rule a disappearance of TBII-activity was combined with a functional remission (22 of 25 patients). Prolonged demonstration of TBII-activity in conjunction with persistence of hyperthyroidism should lead to ablative measures. In contrast to this medical therapy should be finished in patients with immunological and functional remission. Though in the further follow-up a recurrence of the immunological base of the disease with a functional and clinical relapse is possible.

Autoantibodies↗

Predictive value of the index of desirable body weight for total body fat mass as measured by dilution of tritiated water--problems and limitations.

The index of desirable body weight is currently used for classification of patients' weights. We examined how it is related to the degree of adiposity, and whether it can serve in the prediction of body fat to the same degree as Quetelet's index. Sixty-five women and 142 men comprising a wide range of weight indices were studied. Body fat (F) was measured by the tritium dilution technique with a precision of +/- 1.26 kg. Regressions of F/W0 on the index of desirable weight W/W0 gave a correlation coefficient of 0.969 for women and 0.939 for men. Regressions of F/H2 on Quetelet's index W/H2 had correlation coefficients of the same order, i.e. 0.971 for women and 0.936 for men. Hence both indices are equally powerful for calculation of body fat within the study population. Further progress was achieved by multiple regression of F on W and W0 which yielded correlation coefficients of 0.976 for women and 0.953 for men. The residual standard deviation reflecting the mean difference between calculated and estimated fat was 3.4 kg for women and 3.8 kg for men. Despite this self-consistency, prediction of body fat for persons outside the study population is only possible within wide limits. These are given by about twice the residual standard deviation. Therefore, prediction of body fat from weight indices can only be used for detection of larger abnormalities in body composition.

Adult↗

[Cardiologic findings in newly manifested type II diabetics of the diabetes intervention study].

In 1,126 newly manifested primarily purely dietetic manageable type II-diabetics (628 men, 498 women) of the diabetes intervention study (DIS) at the age from 30 to 55 years the prevalence of the ischaemic heart disease was established with the help of the ECG in rest (Minnesota code) and in 70% of the test persons by an additional electrocardiography after work. Including the two parameters in 9.2% of the diabetic men and 26.1% of the women electrocardiographic findings of an ischaemic heart disease could be proved. The proportion of pathological findings of the ECG increased with age. While the proportion of a probable ischaemic heart disease (code 1.1-1.2) in the ECG in rest and with 1.4% the same size in the two sexes, in women, the percentage of a possible ischaemic heart disease (code 1.3, 4.1-4.3/5-5.3/8.3) prevailed with statistical significance after the 45th year of age. The at present numerically largest study on newly detected diabetics of type II gives evidences to the previous cardial lesion when the diabetes is manifest at medium age on the basis of the homogeneity of the number of patients.

Adult↗

Formation of prostacyclin and thromboxane in man as measured by the main urinary metabolites.

Excretion of 2,3-dinor-6-ketoprostaglandin F1 alpha and 2,3-dinorthromboxane B2, the main urinary metabolites of prostacyclin and thromboxane, was evaluated by gas chromatography-mass spectroscopy and radioimmunoassay, respectively, at various conditions in man. In healthy young males excretion of 2,3-dinor-6-ketoprostaglandin F1 alpha was of little variability, whereas urinary 2,3-dinorthromboxane B2 showed marked interindividual but moderate intraindividual variations. The ratio of urinary 2,3-dinorthromboxane B2 to thromboxane B2 in young males was about 15. Excretion of 2,3-dinor-6-ketoprostaglandin F1 alpha in women of reproductive age was higher (155 +/- 23 ng/g creatinine, P less than 0.005) than in postmenopausal women (97 +/- 24 ng/g creatinine) and in men (78 +/- 7.6 ng/g creatinine) and increased significantly during pregnancy (1st trimester 230 +/- 50 ng/g creatinine; 3rd trimester 522 +/- 53 ng/g creatinine). Urinary 2,3-dinorthromboxane B2 showed no gender differences and no directed change was observed during pregnancy. In neonates urinary 2,3-dinorthromboxane B2 (6.328 +/- 1.210 ng/g creatinine) was high in their 3rd day of life and decreased rapidly thereafter. This pattern paralleled the behavior of 6-ketoprostaglandin F1 alpha. In young male smokers and non-smokers excretion of 2,3-dinor-6-ketoprostaglandin F1 alpha was not significantly different, whereas urinary 2,3-dinorthromboxane B2 was elevated in smokers (609 +/- 61 versus 351 +/- 41 ng/g creatinine, P less than 0.001). Values are mean +/- S.E.

6-Ketoprostaglandin F1 alpha↗

Effects on prostanoid formation and pharmacokinetics of dazmegrel (UK-38,485), a novel thromboxane synthase inhibitor, in man.

The pharmacokinetics of dazmegrel (UK-38,485), a novel selective thromboxane synthase inhibitor, and its effects on in vivo prostanoid formation were studied in a 2 weeks, multiple dose, placebo controlled, double blind trial in man. The drug was well tolerated. After dazmegrel 50-200 mg p.o. peak plasma levels of 0.7-3 mu/ml were reached within 1 hr. Elimination was of first order with a half life of 0.88 +/- 0.17 hr. Platelet count and bleeding time were unchanged by all regimes of dazmegrel used (100 and 200 mg b.i.d.; 50, 100 and 200 mg t.i.d.). Serum thromboxane (TXB2) was more than 95% suppressed one hour after all doses studied, but 200 mg t.i.d. were needed suppress circadian serum TXB2 profiles more than 90% at all times. Urinary excretion of 2,3-dinor-TXB2 (TXA2-M) fell by over 90%. An increase in the excretion of 2,3-dinor-6-keto-PGF1 alpha (PGI2-M), the major metabolite of prostacyclin, was largely transient and fell short of significance at all times. The ratio of TXA2-M to PGI2-M was lowered from about 5.0 to 0.2 and sustained throughout treatment. Dazmegrel selectively blocks in vivo and ex vivo TXA2 formation. Redirection of endoperoxides from total body TXA2 formation into prostacyclin formation is only minor under basal conditions.

Adult↗

The prostacyclin/thromboxane balance is favourably shifted in Greenland Eskimos.

The rare incidence of cardiovascular disease in Eskimos has been ascribed to their diet rich in eicosapentaenoic acid (EPA, C20:5n-3) and hence a possible formation of trienoic prostanoids. In this study we compare endogenous formation of prostacyclin (PGI), which is formed by the endothelial cell, and thromboxane (TXA), which is formed by platelets in 20 Eskimos and 20 age and sex matched Danish controls by measurement of the main urinary metabolites. Considerable formation of bioactive PGI3 from dietary EPA was shown in Eskimos, which was barely detectable in the controls. Furthermore synthesis of PGI2 was significantly higher in Eskimos in spite of a markedly lower arachidonate content in membrane lipids. In contrast formation of TXA2,3 was lower in Eskimos as compared to the Danish controls. We conclude, that the balance between PGI and TXA, which may regulate the interaction of platelet and vessel wall, is favourably shifted in Greenland Eskimos to an antithrombotic state.

Adult↗

Comparison of the urinary metabolites of prostacyclin and thromboxane of the 2- and 3-series in a Japanese fishing and a Japanese farming village.

We measured PGI2-, PGI3-, and TXA2/3-M (the main urinary metabolites of prostacyclin and thromboxane of the two and three series) in 24-hour urine in a fishing village (21 participants) and a farming village (19 participants) in Japan, expecting to find more PGI3-M in the fishing village than in the farming village. The food consumption for three consecutive days prior to a blood collection was recorded and analyzed for eicosapentaenoic acid (EPA) content. Urine was collected for 24 hours prior to the blood sampling. When our studies were performed (April, 1985), catches of fish were the lowest on record around the fishing village, and the consumption of EPA in the fishing village was less than half of that in the farming village. EPA levels in red cell membrane phospholipids were higher in the fishing village than in the farming village. PGI2-, PGI3-, and TXA2/3-M levels were higher in the farming village than in the fishing village. There was a significant correlation between PGI2- and PGI3-M (r=0.80, n=40) and between PGI3-M and the EPA consumption during the day of urine collection (r=0.52, n=40). We conclude that PGI3 production is probably dependent less on the levels of EPA in tissues estimated by the EPA levels in red cell membranes than on the EPA consumption at the moment.

Adult↗

Animal studies on the in vivo stability of 211At-labelled albumin particles.

The alpha-emitter astatine-211 appears as one of the most suitable representatives for radiotherapy owing to its excellent decay properties. We report the studies in mice on the stability of the astatine bond to HSA-particles. Microspheres stick fast in the lung capillaries. There is a comparatively very slow decrease of radioactivity in the lungs. The 211At-labelled microspheres appear quite stable in vivo compared with a series of other biomolecules and so give a potential possibility for using the excellent radiophysical features of 211At in endogenous therapy of malignant tumours.

Animals↗

Protein-chemical identification of the major cleavage sites of the Ca2+ proteinase on murine vimentin, the mesenchymal intermediate filament protein.

Neutral thiol proteinases (calpains), activated by calcium are involved in the intracellular turnover of intermediate filaments but the precise position of the cleavage points has remained unknown. Here we identify by direct sequence analysis the major cleavage sites found when murine vimentin is digested by limited proteolysis in vitro with calpain purified from porcine kidney. Contrary to some previous suggestions, no absolute sequence specifity could be detected although 10 specific sites have been identified. This result is in line with the cDNA derived amino-acid sequence of a calpain, which pointed to a similarity of the catalytic site with the active sites in papain, cathepsin and actinidin. However, all major cleavage sites are located within regions of the vimentin molecule, which in current models of intermediate filament structure are thought to be non-helical: the amino-terminal headpiece, the carboxy-terminal tailpiece and the spacer separating the two major coiled-coil domains. The sequence information about the cleavage sites was extended to provide the amino-terminal 119 residues of murine vimentin.

Amino Acid Sequence↗

Low and high risk coronary patients discriminated by blood platelet fatty acid composition.

The distribution of 11 long-chain fatty acids in platelet phospholipids were subjected to multivariate statistical analysis with groups of high and low risk coronary patients and controls. The alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) had significant explanatory power between the groups. As has been anticipated from studies in Eskimos, the EPA fraction was low in coronary patients. It was lower in high risk patients than in low risk patients, and lower in patients below rather than above, 60 years of age. Young high risk patients had 1.2 +/- 0.2% (Mean, SE) EPA against 1.8 +/- 0.2% in young controls, (p = 0.035). Old low risk patients had the highest EPA and also the highest DHA, 2.9 +/- 0.3% against 2.3 +/- 0.2% in controls. The ALA was low in low risk patients. Patients with low platelet EPA and high serum cholesterol should be included in trials with EPA rich diets.

Aged↗

Vesicular stomatitis virus produced from infected LSTRA lymphoma cells bear tyrosine protein kinase activity (p56).

Murine LSTRA lymphoma cells contain a very active tyrosine protein kinase of 56 kDa (p56) which is not related to any of the other known tyrosine kinases. In the past the purification and characterization of the p56 have been hampered because of the low amount of this protein in LSTRA membranes. In this study, we have utilized a different approach for purification which consisted of trapping the protein in the membrane of vesicular stomatitis virus. Incubation of the virions with [gamma-32P]ATP resulted in the phosphorylation of p56 on tyrosine residues. Moreover, the phosphopeptide digest profile of vesicular stomatitis virus-p56 was identical to that observed with authentic LSTRA-p56. The p56 from such virions could be resolved from other proteins by two-dimensional gels, and furthermore, such virions have been used to prepare several antisera directed against the p56.

Amino Acids↗