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Biomedical subjects

T Koschinsky

Publications and source records attributed to T Koschinsky.

At least 55 records · Page 3Linked to original sources
PubMed1981

Regulation of diabetic serum growth factors for human vascular cells by the metabolic control of diabetes mellitus.

Serum factors from non-ketotic poorly controlled non-insulin-dependent diabetic patients stimulated growth and protein synthesis of human arterial smooth muscle cells and fibroblasts by 15-42%, compared to serum factors from well controlled diabetics. In contrast, the growth stimulating effect of pooled sera from well controlled diabetics did not differ from the effect of normal sera. Single sera from the same diabetics before and after improvement of the metabolic control stimulated cell growth to a similar degree as the respective pooled sera from different diabetic populations. As far as increased growth stimulation of vascular cells is related to increased angiopathic risk in diabetics, this metabolic regulation of growth factors supports the demand for a continuous optimal control of diabetic metabolism.

Cells, Cultured↗
PubMed1980

Increased growth stimulation of fibroblasts from diabetics by diabetic serum factors of low molecular weight.

Serum factors from non-ketotic poorly controlled diabetic patients when compared to serum factors from normal subjects, stimulate growth and protein synthesis of cultured fibroblasts from diabetic patients by 25-50%. This increased growth stimulating effect of diabetic serum is mainly related to low molecular weight components (mol. wt. < 12,000 daltons), but not to insulin or glucose. These low molecular weight components of diabetic serum are effective only in combination with serum factors of a molecular weight > 12,000 daltons which are essential for initiation and continuous stimulation of cellular growth. As the growth stimulation by diabetic serum factors with a molecular weight < 12,000 daltons does not differ from comparable normal serum factors, the relevance of these serum factors (e.g. growth hormone, lipoproteins) for the increased growth stimulation of mesenchymal cells in diabetes mellitus seems to be only of limited importance. In as much as these in vitro results represent the in vivo situation, chronic exposure of vascular cells from diabetics to these serum factors could be related to the increased angiopathic risk in diabetes mellitus.

Cell Division↗
PubMed1979

Increased growth of human fibroblasts and arterial smooth muscle cells from diabetic patients related to diabetic serum factors and cell origin.

Fibroblasts from 3 diabetic patients (DF) grew faster, resulting in higher cell counts in the stationary phase than fibroblasts from 3 age-matched healthy volunteers (NF). This difference was apparent when DF or NF were cultured in either diabetic (DS) or normal serum (NS). Diabetic serum increased growth of both DF and NF compared with normal serum. Total protein content per plate paralleled the increase of cell number per plate in relation to cell origin and serum type. DS increased growth and total protein per plate in the arterial smooth muscle cell line from a non-diabetic patient in a way similar to in DF and NF. It is concluded that increased growth of DF in vivo could result in an increased turnover of vascular cells with a shortened replicative lifespan, leading to an accumulation of basal lamina. This effect would be even further accentuated by exposure of DF to DS. Taken together with the increased protein synthesis the accelerated development of diabetic angiopathy could be the final consequence.

Adolescent↗
PubMed1977

[Treatment of primary hyperlipoproteinemia type IIb and IV. Comparison of the lipid lowering effect of phenformin, clofibrate, and a combination of both (author's transl)].

22 outpatients with primary hyperlipoproteinemia type IIb and IV were treated in periods of eight weeks as follows: placebo; 0,15 g phenformin/day; 0,15 g phenformin + 1,5 g clofibrate/day; 1,5 g clofibrate/day; placebo. Compared to the first placeboperiode the serumtriglycerides were significantly lowered by phenformin (about 26%), by the combined treatment with phenformin + clofibrate (60%) and by clofibrate (51%) after eight weeks of treatment. The serumcholesterol was significantly lowered by phenformin (10%) and by the combined treatment with phenformin and clofibrate (14%), but not significantly by clofibrate (8%). After eight weeks of treatment with phenformin alone or in combination with clofibrate the body weight decreased significantly (1,9% or 1,4%). These changes in body weight were not related to changes in blood lipids. In conclusion, the combined treatment with 0,15 g clofibrate/day was more effective in lowering increased serum lipids than the treatment with phenformin or clofibrate alone.

Adult↗
PubMed1977

[Treatment of primary hyperlipoproteinemias of type IIB and IV with butylbiguanide and clofibrate (author's transl)].

21 patients with primary hyperlipoproteinemias of type IIb and IV were treated for 8 weeks with placebo, 8 weeks with 0.3 g butylbiguanide and 1.5 g clofibrate/day and then for 8 weeks with 1.5 g clofibrate/day. In 12 patients a second placebo phase of 8 weeks followed. After 8 weeks of combined treatment with butylbiguanide and clofibrate the serum triglycerides decreased from 725 mg to 269 mg/100 ml. During the following period of clofibrate treatment the serum triglycerides increased after 4 and 8 weeks to 326 mg and 306 mg/100 ml respectively. The combined treatment with 0.3 g butylbiguanide and 1.5 g clofibrate/day is more effective in lowering elevated serum triglycerides and cholesterol than 1.5 g clofibrate alone.

Adult↗
PubMed1977

Interaction between high density and low density lipoproteins uptake and degradation by cultured human fibroblasts.

High density lipoprotein (HDL) inhibited the binding (trypsin-releasable radioactivity), internalization (cell-associated radioactivity after trypsinization), and degradation (TCA-soluble non-iodide radioactivity) of (125)I-low density lipoprotein ((125)I-LDL) by cultured normal human fibroblasts. At HDL:LDL molar ratios of 25:1 (protein ratios about 5:1), these parameters were reduced by about 25%. Unlabeled LDL was about 25 times more effective in reducing (125)I-LDL binding, implying that if HDL and LDL bind at common sites the affinity of HDL for these sites is very low or that the interaction is on some other basis. The fractional reduction in (125)I-LDL binding at a given HDL: (125)I-LDL ratio was independent of (125)I-LDL concentration and occurred equally with fibroblasts from a subject with homozygous familial hypercholesterolemia. Reciprocally, the binding, internalization, and degradation of (125)I-HDL were reduced by LDL. Preincubation of fibroblasts with HDL (or LDL) reduced the subsequent binding of (125)I-LDL (or (125)I-HDL) during a second incubation. In other studies HDL reduced the net increase in cell cholesterol content induced by incubation with LDL. HDL alone had no net effect on cell cholesterol content. These findings suggest that HDL reduces both the high affinity and the low affinity binding of LDL to human fibroblasts and that this in turn reduces the internalization and degradation of LDL. The effect of HDL on the LDL-induced changes in cell cholesterol content could be in part on this basis and in part on the basis of an HDL-stimulated release of cholesterol from the cells. These effects of HDL in vitro may be relevant to the negative correlations reported from in vivo studies between plasma HDL concentration and both body cholesterol pool size and the prevalence of clinically manifest atherosclerosis but further studies will be needed to establish this.

Binding Sites↗
PubMed1977

A comparative study of surface binding of human low density and high density lipoproteins to human fibroblasts: regulation by sterols and susceptibility to proteolytic digestion.

Binding of 125I-low density lipoprotein (LDL) and 125I-high density lipoprotein (HDL) was determined in cultured human fibroblasts from a normal subject and two subjects with homozygous familial hypercholesterolemia (HFH). Binding was assayed at 0 degree C to minimize the internalization of labeled lipoproteins. The binding of LDL and of HDL were compared following interventions reported to affect LDL binding in normal fibroblast. LDL binding to normal cells increased two to three fold 24 hours after transfer from medium containing whole fetal calf serum to medium containing lipoprotein-deficient fetal calf serum. This increase was completely blocked in the presence of cycloheximide (200 microgram/ml) or 7-ketocholesterol (2.5 microgram/ml). This increased capacity of normal fibroblasts to bind LDL could be reduced 70-80% by a subsequent 18-hour incubation with cholesterol (50 microgram/ml) or 7-ketocholesterol (2.5 microgram/ml). In contrast, no significant change in HDL binding to normal fibroblasts was observed after any of these interventions. HFH cells to show any significant change in either LDL binding or HDL binding following these interventions. These results suggest that HDL binding sites on normal fibroblasts are for the most part distinct from LDL binding sites. They also support the conclusion that LDL binding sites on HFH cells are for the most part qualitatively different from those on normal cells.

Binding Sites↗
PubMed1976

A mechanism by which high-density lipoproteins may slow the atherogenic process.

There is a well-documented negative correlation between plasma concentrations of high-density lipoproteins (H.D.L.) and risk of clinically evident atherosclerosis. This may relate to the postulated role of H.D.L. in the transport of cholesterol out of cells. Studies of the metabolism of lipoproteins by arterial smooth-muscle cells suggest that a second mechanism also operates, H.D.L. binds to the surface of porcine arterial smooth-muscle cells as effectively as low-density lipoprotein (L.D.L.) but is internalised and degraded much more slowly. When incubated with L.D.L. these cells show a net increment in cholesterol content. However, cells incubated with equal or higher concentration of H.D.L. under comparable conditions show no cholesterol accumulation. The presence of H.D.L. in the medium partially inhibits uptake and degradation of L.D.L. and, most important, also partially suppresses the net increment in cell sterol content induced by L.D.L. The demonstrated interaction of H.D.L. and L.D.L. could be a second mechanism contributing to the apparent protective effect of high plasma-H.D.L. concentrations in relation to atherogenesis.

Animals↗