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Biomedical subjects

H Schulte

Publications and source records attributed to H Schulte.

At least 127 records · Page 7Linked to original sources

About the effect of risk factors on the structure and the proliferation of arterial wall cells. Part 1: Changes in structure and proliferation of cultivated aortic smooth muscle cells from hypertensive-diabetic rats.

In cultivated aortic smooth muscle cells (SMC) from normal or hypertensive-diabetic rats respectively, two types of cells, small SMC and large ones, were observed. The differences between the surface areas, form factors and nucleus-plasma relations of the small and the large cells, measured by morphometric methods are evident. The ratio of small to large cells originating from the normal group was 87%: 13%, and of those originating from the hypertensive-diabetic group 76%: 24%. The percentages of polynuclear cells from the normal group were 3.9% and from the hypertensive-diabetic group 6.1%. The small cells from hypertensive-diabetic rats proliferated faster (3H-thymidine labeling index 23.7%) than those from the control rats (3H-thymidine labeling index 12.9%). Their large cells showed on the contrary a trend to slower proliferation.

Animals↗

About the effect of risk factors on the structure and the proliferation of arterial wall cells. Part 2: Changes in structure and proliferation of cultivated aortic endothelial cells from hypertensive minipigs.

Cultured aortic endothelial cells (EC) from normotensive and hypertensive minipigs were studied in the second passage. Cytological measurements performed on confluent cultures of the same age in the second subculture revealed significant smaller surface areas and circumferences of EC and of their nuclei in the hypertensive group compared to those in the normotensive control group. The percentage of polynuclear EC was higher in cultures from hypertensive animals than in cultures from normotensive ones. EC derived from hypertensive minipigs differed from those of normotensive animals by a higher rate of proliferation as shown by 3H-thymidine labeling of the cells and by comparison of growth curves.

Animals↗

Psychiatric implications of basic and clinical studies with corticotropin-releasing factor.

Corticotropin-releasing factor (CRF) is a newly sequenced neuropeptide thought to be a principal stimulus to pituitary corticotropin (ACTH) secretion. Evidence obtained from laboratory animals and primates is reviewed which indicates that CRF not only stimulates the pituitary-adrenal axis but also influences several aspects of CNS function which may be of relevance to psychiatric illness. Clinically, experience in administering ovine CRF to more than 150 individuals shows that CRF can be helpful in resolving differential diagnostic dilemmas in patients with various disorders of the hypothalamic-pituitary-adrenal axis and in furthering an understanding of the pathophysiology of conditions such as Cushing's disease and depression.

Adrenocorticotropic Hormone↗

The effects of cigarette smoking on serum levels of HDL cholesterol and HDL apolipoprotein A-I. Findings of a prospective epidemiological study on employees of several companies in Westphalia, West Germany.

In preventive studies of company employees in Westphalia, HDL cholesterol was measured in the sera of 4933 men and 2365 women, as well as HDL apolipoprotein A-I in the sera of 3509 men and 1648 women. Three subgroups were compared: non-smokers = persons who have never smoked; ex-smokers = persons who do not smoke at present but did in the past; smokers = persons who smoke cigarettes at present. Mean values for HDL cholesterol and for HDL apolipoprotein A-I were significantly lower in smokers than in non-smokers or in ex-smokers, while there were no differences between the last two groups. These differences appeared in both sexes but were more pronounced in women than in men. To answer the question whether the observed differences are caused by the consumption of cigarettes by itself or whether they are caused by the presence of other risk factors, further subgroups were compared to assess the influence of the risk factors obesity, hypertension, hypercholesterolaemia, hyperglycaemia and hyperuricaemia. It was found that - regardless of the presence of no, one, two or more risk factors - the frequency of probands with low HDL cholesterol values (less than 0.907 mmol/l (men); less than 1.166 mmol/l (women] was about 10% higher in smokers than in non-smokers or ex-smokers. Subgroups based on the number of risk factors did not exhibit the same clear distribution for apolipoprotein A-I values as were seen for HDL cholesterol. The results are interpreted in the light of the existing literature.

Apolipoprotein A-I↗

HDL phosphatidyl choline and risk-factors of coronary heart disease.

As part of our epidemiological study of employees in Westphalia, the concentration of HDL phosphatidyl choline was measured in 1546 men and 778 women. The results were analysed in relation to the corresponding HDL cholesterol values, as well as the various risk factors for coronary heart disease. HDL phosphatidyl choline values were found to be age independent, higher in women than in men (p les than 0.001), and lognormally distributed in both sexes (men: mean 1.162 mmol/l, median 1.13 mmol/l, minimum 0.60 mmol/l, maximum 2.46 mmol/l; women: mean 1.370 mmol/l, median 1.34 mmol/l, minimum 0.55 mmol/l, maximum 2.46 mmol/l). A positive correlation (p less than 0.001) was found in both sexes between HDL phosphatidyl choline and HDL cholesterol (men: r = 0.588; women r = 0.605). A negative correlation was found in both sexes between HDL phosphatidyl choline values and body weight (men: r = -0.102 (p less than 0.001) women: r = -0.129 (p less than 0.001); and in men, but not in women, there was a negative correlation between HDL phosphatidyl choline values and triglycerides (men: r = -0.190 (p less than 0.001) women: r = -0.042). A negative correlation between HDL phosphatidyl choline and cigarette smoking was found only in female smokers (r = -0.121 (p less than 0.05). The correlation coefficients between HDL cholesterol and triglycerides as well as HDL cholesterol and relative body weight in both sexes were clearly higher than the corresponding correlation coefficient of HDL phosphatidyl choline. In men as well as in women the HDL phosphatidyl choline/HDL cholesterol ratio decreased with increasing HDL cholesterol values or decreasing triglyceride values in blood serum.

Adolescent↗

The relationship of lipoprotein (a) (Lp(a)) to risk factors of coronary heart disease: initial results of the prospective epidemiological study on company employees in Westfalia.

Lp(a) concentrations were determined in 987 male and 477 female company employees in Westfalia, in the age range 17-70 years. These values were then related to age and to the following risk factors: obesity, smoking, hypertension, hypertriglyceridaemia, hypercholesterolaemia, hyperbetalipoproteinaemia, hypoalphalipoproteinaemia, hyperglycaemia and hyperuricaemia. The Lp(a) values showed a similar markedly skewed distribution for both men and women. The median for men was 0.039 g/l, for women 0.050 g/l. In both sexes only about 25% of all Lp(a) values were above 0.10 g/l. Raised Lp(a) values (greater than 0.30 g/l) were found in 6.5% of males and in 6.1% of females. A significantly higher frequency of raised Lp(a) values (greater than 0.30 g/l) was found in: post-menopausal women (11.3% as against 4.1%, p less than 0.01); females with hypercholesterolaemia (19.0% when cholesterol values were greater than or equal to 6.73 mmol/l, 10.8% when cholesterol values were between 5.70-6.72 mmol/l, 3.0% when cholesterol values were less than 5.70 mmol/l, p less than 0.001); and females with hyperbetalipoproteinaemia (22.6% when LDL cholesterol values were greater than or equal to 4.92 mmol/l, 5.0% when LDL cholesterol values were less than 4.92 mmol/l, p less than 0.001). 12.0% of men with hypoalphalipoproteinaemia (HDL cholesterol values less than 0.907 mmol/l) had Lp(a) values greater than 0.30 g/l, as against 5.5% of men with HDL cholesterol values greater than or equal to 0.907 mmol/l (p less than 0.01). This percentage rate increased to 16.9% when hypertriglyceridaemia (greater than or equal to 2.28 mmol/l triglycerides) was also present. All other risk factors which were examined and their combinations had no significant influence on the prevalence of raised Lp(a) concentrations.

Adult↗

HDL phosphatidyl choline and cigarette smoking.

The influence of cigarette smoking on the concentration of HDL phosphatidyl choline was tested in 1,546 male and 778 female employees in Westfalia, and the results were compared with the influence of cigarette smoking on the concentration of HDL cholesterol. Three subgroups were established for comparison: non-smokers = persons who had never smoked; ex-smokers = persons who had in the past been smokers but were now non-smokers; and smokers = persons who at present smoked cigarettes. Neither male nor female smokers proved to have different HDL phosphatidyl choline values when compared to non-smokers or ex-smokers, whereas male and female smokers were found to have decreased HDL cholesterol values when compared to non-smokers (p less than 0.01) or ex-smokers (p less than 0.05). In female smokers a correlation was found between HDL phosphatidyl choline values and the number of cigarettes smoked every day (r = -0.12, p less than 0.05).

Adolescent↗

Apolipoprotein E polymorphism and hyperlipidemia.

We tested apolipoprotein E phenotypes in 1557 normolipidemic factory workers and 822 hyperlipidemic hospital patients. We distinguished six different apolipoprotein E phenotypes and determined their frequencies in normolipidemia (factory workers), hypertriglyceridemia, hypercholesterolemia, and mixed hyperlipidemia. For the three homozygous phenotypes E3/3, E4/4, and E2/2, the percentage distribution in the normolipidemic group was 62.2%, 2.2%, and 0.9%, respectively; for the three heterozygous phenotypes E4/3, E3/2, and E4/2, we determined frequencies of 19.9%, 11.7%, and 2.9%, respectively. A higher prevalence of E2/2 homozygosity was observed in hypertriglyceridemic persons (2.5%) and persons affected by mixed hyperlipidemia (5.0%). E4/4 homozygosity occurred more often among hypercholesterolemic patients (5.0%) than normolipidemic persons (2.2%). These data suggest that E2/2 homozygosity and E4/4 homozygosity both predispose to hyperlipidemia. Patients affected by mixed hyperlipidemia should be investigated for their apolipoprotein E polymorphism because of the possible linkage of apolipoprotein E2/2 homozygosity, hyperlipidemia, and atherosclerosis.

Adult↗

[The Münster study of intensive induction and consolidation therapy without maintenance therapy of acute myeloid leukemia. Results of 93 patients--cellular determinants for response and length of remission].

A 9-day high-dose 3-drug induction regimen including ARA-C, DNR, and TG at special time sequencing was given to 93 patients with AML, 15-74 (median 52) years old. After 1-2 courses for remission induction and, if possible, 2 identical courses of consolidation, no further therapy was applied during remission. Complete remission (CR) was achieved in 71% of all patients and in 74% of responders by 1 course only. Median remission duration is at 1 year with 13 patients in continuous CR for 13-38 (median 24) months. Patients completing consolidation reached a median remission duration of 22 months and those with rapid response to 1 induction course and with complete consolidation 38+ months. Patients monitoring included bone marrow DNA-histograms by flow cytometry, blood counts, percentage, and absolute number of blasts in bone marrow and LDH in serum. Among pretherapeutic parameters only LDH (inversely) correlated with CR duration. In contrast during early therapy rapid blast reduction, decrease of S-phase-index and of LDH as well as short recovery time of platelets and neutrophils predicted for low risk (when high risk included non-response and early relapse). Thus, monitoring of early cellular response parameters reflecting cellularity and proliferation seems to provide important individual determinants of therapeutic outcome.

Adolescent↗

Intensified remission induction therapy for acute nonlymphocytic leukemia (ANLL). Treatment report on 60 patients.

Sixty patients with ANLL were given intensified remission induction therapy consisting of thioguanine, cytosine arabinoside and daunorubicin (TAD). The mean age of patients was 47.6 years (range 18 to 74 years). Basing on leukemic cell kinetic data time sequencing of drugs was different from the original TAD protocol. Complete remission (CR) waa achieved in 43/60 patients (72%) with 10 CR in 15 patients over 60 years of age. Seventy-nine percent of the CR were induced by one cycle vs thirty percent reported from the original TAD regimen. The major cause of induction failure--in ten of the 60 patients--was thrombocytopenia refractory to platelet transfusions. Persisting leukemia after two induction cycles was documented in only two patients. Median remission duration by life table analysis is 10 months with 17 patients in continuous CR for 1+ to 22+ months.

Acute Disease↗

Effect of risk factors and antirheumatic drugs on the proliferation of aortic wall cells.

The proliferation of aortic smooth muscle cells (ASMC) of Wistar rats, impaired by risk factors such as arterial hypertension, diabetes mellitus, atherogenic diet and staphylolysin injections and of normal Wistar rats treated with antirheumatic drugs such as prednisolone and acetylsalicylic acid was investigated. The cells of these animals were cultivated, subcultivated, and in the 2nd subcultures the cell numbers/5 ml medium were counted by means of Coulter Counter, and the cells were incubated with [3H]thymidine and the percentage of labelling in 100 or 1000 counted cells was stated. The effect of risk factors such as LDL and staphylolysin and of antirheumatic drugs such as prednisolone, acetylsalicylic acid, D-penicillamine and chloroquine added to the 2nd subcultures of cultivated ASMC of normal minipigs was investigated by the same method. The proliferation of cultivated ASMC of rats impaired by risk factors was accelerated. The proliferation of cultivated ASMC of rats treated with antirheumatic drugs was inhibited. The proliferation of ASMC of minipigs in the 2nd subcultures was activated by addition of risk factors and inhibited by addition of antirheumatic drugs. Antirheumatic drugs given to the rats and added to the medium of the 2nd subcultures of ASMC of normal minipigs inhibit the acceleration of ASMC proliferation induced by simultaneously given risk factors. The proposal to augment up our arsenal of the hitherto existing preventive and therapeutical measures by the application of antirheumatic drugs based on the experimental models referred to is supported by the result of a limited prospective double-blind-study of a sample of 133 male patients after myocardial infarction. The most remarkable result that the acceleration of the ASMC proliferation, the real pathologic process of arteriosclerosis, is inhibited by the application of antirheumatic drugs, at exactly the same time as the acceleration of the fibroblast proliferation, the real pathologic process in rheumatic diseases--ASMC and fibroblast, both being mesenchymal cells--recommends the use of these drugs in the prevention and therapy of human arteriosclerosis. The surprising result of our in-vivo experiments, that the acceleration of the growth of the ASMC induced by risk factors and the inhibition of the growth induced by antirheumatic drugs persist in the subcultures, is explained by the "selection theory" that there are dissimilar kinds of ASMC in normal arteries and that they react differently.

Animals↗

Binding of luteinizing hormone releasing hormone to human serum proteins--influence of a chronic treatment with a more potent analogue of LH-RH.

Binding of 125I-LH-RH and its analogue, 125I-6-D-Leu-10-Des-Gly-Ethylamide-LH-RH (6-D-LH-RH) in male serum was studied in 10 healthy males and in 11 patients with idiopathic gonadotropin deficiency (IGD) before and during treatment with 6-D-LH-RH. Using either equilibrium dialysis (A) or ethanol precipitation (B) 13.57 +/- 0.69% (A) or 19.32 +/- 1.73% (B) of LH-RH and 7.12 +/- 0.86% (A) or 14.56 +/- 1.06% (B) of the analogue were in the bound form, without difference between normal subjects and IGD. Capacity of this binding was high (greater than 9 less than 18 mu-Mol LH-RH/0.06 mMol of protein), affinity very low, and the binding almost completely disappeared following removal of albumins by affinity chromatography. Chronic treatment with 6-D-LH-RH did not alter these binding characteristics. These observations suggest non specific albumin binding of LH-RH in male serum and stress the role of this decapeptide as a rapid modulating regulator of gonadotropin secreting system.

Blood Proteins↗

Studies on the influence of different drugs upon the proliferative answer of ASMC and fibroblasts in culture depending on drug concentration and exposition time.

We investigated the proliferation of fibroblasts and A.S.M.C. in culture as a function of concentration and exposition time of D-Penicillamine, Prednisolone, Acetylsalicylic Acid and Chloroquine. For every drug we found a concentration that caused only small initial inhibition of cell growth but did not alter the kind of further proliferation compared with controls. This "optimal inhibiting drug concentration" was characteristic of the drug but uncharacteristic of the cell type. Lower concentrations lead to a slight increase of proliferation, higher concentrations to a decrease of proliferation and finally after specific times of exposure to cell degeneration. Chloroquine showed no proliferation increasing effect even in doses much lower than the equivalent human daily drug dose. The equivalent human daily drug dose for Chloroquine was much higher than the optimal inhibiting drug concentration whereas that for the other drugs was the same as the optimal inhibiting drug concentration. For each drug there was a linear correlation between the degree of inhibition of cell proliferation and the logarithm of drug concentration on every occasion the cell growth was examined. All the relationships demonstrated were true of both fibroblasts--and A.S.M.C.--cultures, which indicates that there is no connection between the type of cell and its reaction to these, specific, chemical, drugs. Our results show that culture methods are suitable for the study of cell drug interactions.

Animals↗