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H Ditschuneit

Publications and source records attributed to H Ditschuneit.

At least 163 records · Page 9Linked to original sources

Two separate receptors for insulin and insulinlike growth factors on arterial smooth muscle cells.

Insulin and insulinlike growth factors (IGF) are related polypeptides that have similar biological activities. Both factors produce metabolic effects as well as growth effects. Most cells have separate receptors for IGF and insulin. In the present study we have demonstrated specific IGF receptors in cultured smooth muscle cells of rat aorta. The properties and specificity of these receptors were compared with those of the insulin receptor in the same cell system. The specific binding of both 125I-IGF and 125I-insulin binding in the order of potency: insulin proinsulin IGF. The potency of IGF in displacing 125I-insulin was rapid and reversible. Maximal 125I-IGF binding occurred at 20 degrees C with a specific binding of 10%. At this temperature specific 125I-insulin binding was 1.3% and occurred in biphase. The pH optimum for 125I-IGF binding was between pH 7 and 8. Both receptors show a high degree of specificity. IGF, insulin and proinsulin competed for 125I-IGF binding in the order of potency: IGF proinsulin insulin. The potency of insulin in displacing 125I-IGF was about 2000 times lower than that of IGF itself. In addition, IGF, insulin and proinsulin competed for 125I-insulin was about 450 times lower than that of insulin. These results indicate two separate binding sites for insulin and IGF on arterial smooth muscle cells.

Animals↗

[Sonographic diagnosis of malignant small intestine carcinoid tumor. A case report].

A 47 year old male patient came to our attention for severe anaemia. Although Gujak test for occult blood in the stool was repeatedly positive, x-ray films and endoscopic methods did not yield a definite diagnosis. Ultrasound only was able to identify a mass in the small intestine. Intraoperatively the diagnosis was confirmed; the tumour was a highly malignant carcinoid on pathologic examination.

Carcinoid Tumor↗

Characterization of insulin binding sites in cultured smooth muscle cells of rat aorta.

Insulin receptors could be demonstrated in cultured smooth muscle cells of rat aorta. The specific binding of 125I-insulin was time-, temperature- and pH-dependent. The optimal temperature for our studies was 12 degrees C. At this temperature maximal specific binding was 0.5% of total counts at 120 min incubation. The pH-optimum for the binding process was between 7.5 and 8. Degradation of 125I-insulin at 12 degrees C was 14%, no degradation of binding sites could be measured at this temperature. Dissociation of 125I-insulin was rapid. 50% of the labeled hormone remained associated with the cells. Half-maximal inhibition of 125I-insulin binding was produced by insulin at 4 X 10(-11) mol/l. Scatchard-analysis gave curvilinear plots, that may suggest negative cooperativity. Specificity of binding was studied in competition experiments between 125I-insulin, insulin, proinsulin, insulin-like growth factors and human growth hormone. Half-maximal inhibition of 125I-insulin binding was produced by proinsulin at 2 X 10(-9) mol/l and by insulin-like growth factors at 9 X 10(-9) mol/l. Human growth hormone had no significant effect on the insulin binding.

Animals↗

Receptors for insulin and insulin-like growth factor in cultured arterial smooth muscle cells depend on their growth state.

The binding of 125I-labelled insulin and 125I-labelled insulin-like growth factor (IGF) to cultured arterial smooth muscle cells from rats was studied during various growth states of the cells. The level of binding of 125I-labelled insulin to the cells was low in growing cells and high in stationary cells. The level of 125I-labelled IGF binding to the cells was high in growing cells and low in stationary cells. In addition, the effect of unlabelled IGF and insulin on the binding of both 125I-labelled hormones to the cells was examined during various growth states. In growing cells insulin displaced 125I-labelled insulin from its binding sites; IGF competed weakly with 125I-labelled insulin for the binding sites. In parallel, IGF displaced 125I-labelled IGF binding whereas insulin competed weakly with 125I-labelled IGF for the binding sites. In stationary cells both hormones displaced 125I-labelled IGF binding. Insulin-like growth factor also displaced 125I-labelled insulin binding whereas insulin could not significantly displace 125I-labelled insulin from the binding sites. Insulin only competed with 125I-labelled insulin for the binding sites after removal of the fetal calf serum from the culture medium.

Animals↗

Regulation of receptors for insulin-like growth factors in cultured arterial smooth muscle cells by thyroid hormone.

The effect of tri-iodothyronine (T3) on the binding of 125I-labelled insulin-like growth factors (IGF) to cultured arterial smooth muscle cells was investigated. When cells which were grown to confluency were incubated with 125I-labelled IGF and different concentrations of T3, low concentrations of T3 (0.1-10 nmol/l) increased the binding of 125I-labelled IGF. High concentrations of T3 (1 mumol/l) could not induce this effect. Scatchard analysis of the binding of 125I-labelled IGF in the presence of different concentrations of unlabelled IGF showed a high-affinity, low-capacity binding system and a second lower affinity, high-capacity binding system. In the presence of T3 (1 nmol/l) Scatchard analysis indicated that the affinity of 125I-labelled IGF to its binding sites was altered. After a 2-h preincubation of the cell layers with Dulbecco's Modified Eagle's Medium containing T3 (1-100 nmol/l), the 125I-labelled IGF binding was enhanced in a dose-dependent manner by T3. Scatchard analysis showed a significant increase in the number of IGF binding sites.

Animals↗

[Ct-morphology and exocrine function in chronic pancreatitis].

A quantitative correlation between computer-tomographic (CT) findings and exocrine pancreatic function following secretin-ceruletide stimulation was performed in 48 patients with chronic pancreatitis; thereby a significant correlation between the degree of morphological changes in CT and the stage of functional impairment was found (r = 0,7841, p less than 0,001). Bicarbonate secretion/h showed the strongest correlation to CT findings (r = -0,7193, p less than 0,001) within the single functional parameters. CT showed a limited sensitivity (50%) in detecting chronic pancreatitis in cases with a slight functional impairment (stage 1). Morphological signs as calcifications, pancreatic duct ectasia were constantly coupled with a severe degree of functional impairment, whereas enlargement and cysts were found throughout the different functional stages.

Adult↗

[Effect of a clofibrate-inositol nicotinate combination on lipids and lipoproteins in primary hyperlipoproteinemia of types IIa, IV and V].

The effect of a combination of clofibrate and inositol nicotinate (Liporeduct forte, Liporeduct) on lipids and lipoproteins in 20 patients with primary hyperlipoproteinemia (10 type IIa, 7 type IV and 3 tyV) was investigated over a period of 16 weeks. The daily doses of clofibrate and inositol nicotinate was 1,5 g and 2,4 g in the type IIa and 1,5 g and 900 mg in the types IV and V. Placebo was given before and after the treatment period. In the type IIa total cholesterol decreased from 345 +/- 35 to 285 +/- 31 mg/dl; the triglycerides were lowered from 121 +/- 12 to 94 +/- 7 mg/dl. These changes were mainly due to a decrease in low density lipoprotein (LDL)-cholesterol by 18% and a reduction in very low density lipoprotein (VLDL)-triglycerides of 42%. In the types IV and V a triglyceride reduction of 30% and 76% could be observed. In both types, these changes were mainly caused by a decrease in VLDL-triglycerides (type IV: -34%; type V -77%). Total cholesterol was influenced insignificant in these two types. High density lipoprotein (HDL)-cholesterol fell in the types IIa and IV; in the type IV an increase of 24% could be observed. Phospholipids and proteins behaved in an analogous fashion. The percentual composition of the lipoprotein fractions VLDL, LDL and HDL didn't change under treatment in the types IIa and IV. In the type V, a shift in the direction of type IV could be observed. The combination of clofibrate and inositol nicotinate was well tolerated.

Clofibrate↗

Changes in the concentration and composition of lipids and lipoproteins in primary hyperlipoproteinemia during treatment with bezafibrate.

The effect of 2-(4-chlorobenzoyl-aminoethyl-phenoxy)-2-methylpropionic acid (bezafibrate, Cedur) at doses of 3 x 150 mg and 4 x 150 mg daily on lipids and lipoproteins in 27 patients (3 type IIa, 7 type IIb, 1 type III, 12 type IV and 4 type V) was investigated over a period of 24 weeks in a single-blind study. The lower dose was administered for the first 12 weeks and then the higher dose was given. Plasma triglycerides were reduced in all types. This was mainly caused by a massive reduction in VLDL triglycerides. Plasma cholesterol decreased in the types IIa, IIb, III as a result of the reduction of the LDL cholesterol. In type IV, the plasma cholesterol concentration remained unchanged because of a significant rise in the LDL cholesterol (+14%). The HDL cholesterol rose in all types, statistically significantly in the type IV. Phospholipids and protein behaved in an analogous fashion. In comparison with a control group, the lipoprotein fractions VLDL, LDL and HDL retained their abnormal composition in the types IIa, IIb and IV even when the lipid concentrations were massively lowered by bezafibrate. The drug treatment only led to a reduction of circulating lipoproteins in the blood, but didn't contribute to a normalisation of the lipoprotein composition. In the type V, a shift in the direction of type IV was observed. Bezafibrate proved to be well tolerated.

Aged↗

[Effect of beta-pyridylcarbinol on lipids and lipoprotein in primary type IIa hyperlipoproteinemia].

The effect of long-term treatment over 16 weeks with beta-pyridylcarbinol (test substance Ronicol 300) on lipids and lipoproteins was investigated in 10 patients with primary hyperlipoproteinemia type IIa. A placebo period preceded and followed the treatment period. The lipoprotein fractions VLDL, DL and HDL (very low density lipoproteins, low density lipoproteins and high density lipoproteins, respectively) were isolated by preparative ultracentrifugation. beta-Pyridylcarbinol reduced total cholesterol from 410 +/- 39 mg/dl to 319 +/- 19 mg/dl (p less than 0.05). The decrease was mainly caused by a reduction in LDL-cholesterol by 25%. The HDL-cholesterol rose only slightly during treatment. The reduction in total triglycerides (132 +/- 12 mg/dl to 110 +/- 12 mg/dl) was less marked. The decrease was attributable to a reduction in VLDL- and LDL-triglycerides. Phospholipids and proteins behaved in an analogous fashion. The composition (in %) of the lipoprotein fractions VLDL, LDL and HDL didn't change under treatment. The typical nicotinic acid flush could be observed in all 10 patients.

Female↗

[Diagnostic significance of pancreatic serum-enzyme patterns after stimulation with secretin in chronic pancreatitis (author's transl)].

The pancreatic serum evocation test with secretin has regained importance now that it is possible to determine immunoreactive trypsin and pancreatic isoamylase. After secretin stimulation there was a significant abnormal increase in serum trypsin (p less than 0.01) in 34 patients with proven chronic pancreatitis associated with mild to moderate dysfunction (groups I-II), no rise if there was marked insufficiency (group III). Patients with steatorrhoea and obstruction in the region of the head of the pancreas formed a special group because, contrary to other patients in groups III, they had marked serum enzyme rise after secretin. In 24 control subjects with a normal pancreas there was no significant change in basal pancreatic serum enzyme levels with secretin stimulation. Trypsin and amylase reaction patterns differed during secretin stimulation, with a rise in the amylase occurring at the expense of pancreas isoamylase.

Adult↗

[Bezafibrate in primary hyperlipidemias (author's transl)].

The effect of long-term treatment over 40 weeks with Bezafibrate on lipids and lipoproteins was investigated in 27 patients with primary hyperlipoproteinemias (hlp) (12 patients with hlp type IV, 7 patients with type IIb, 3 patients with type IIa, 4 patients with type V and 1 patient with type III). Bezafibrate reduced total cholesterol by 16%, whereas HDL-cholesterol increased by 28% and 36% (p less than 0.05). Serumtriglycerides decreased by 59% (450 mg Bezafibrate daily) and by 66% (600 mg Bezafibrate daily) statistically significant (p less than 0.05). In hyperlipidemias type IV, IIb, IIa and V increases of HDL-cholesterol could be observed. The course of LDL-cholesterol was different in the various types of hlp. The postheparin-lipoprotein-lipase (PHLA) was activated by treatment with Bezafibrate from 10.5 +/- 0.7 to 14.7 +/- 0.7 and 15.5 +/- 0.8 mumol FFA/ml/h or by 30% (p less than 0.05). Only few side-effects during treatment with Bezafibrate could be ascertained.

Bezafibrate↗

Upper gastrointestinal hemorrhage from downhill esophageal varices.

Two cases of proximal esophageal varices due to a primary and a recurrent goiter are reported. One of the patients presented with massive upper gastrointestinal hemorrhage 44 years after subtotal resection of a thyroid gland. "Downhill" esophageal varices may serve as collaterals either to bypass superior vena caval obstruction via azygous vein or to drain the superior systemic system to the portal vein when both the superior vena cava and the azygous vein are occluded. They may also arise, as in our bleeding patient, from previous thyroid surgery without any symptoms of superior vena caval congestion. Therefore, downhill varices should be suspected as the origin of upper gastrointestinal hemorrhage not only in patients with obvious superior vena caval obstruction, buy also in any case of thyroid disease or a history of thyroid surgery. If conservative measures are insufficient, emergency management may include balloon tamponade or endoscopic sclerotherapy.

Aged↗

3-Hydroxy-3-methylglutaryl CoA reductase in cultured hepatocytes. Regulation by heterologous lipoproteins and hormones.

Regulation of the key enzyme of cholesterol synthesis, 3-hydroxy-3-methylglutaryl CoA reductase (EC: 1.1.1.34), by heterologous human lipoproteins and hormones was studied in a maintenance culture of rat hepatocytes. The liver cells were cultured under hormone and serum free conditions and maintained differentiated morphology and specific function. Under control conditions total HMG-CoA reductase increased by 50% after 24 h culture compared to 0 h values immediately after isolation. Thereafter a plateau of enzyme activity was reached lasting until 48 h, with a slight decline at 72 h. Concomitantly the "expressed" enzyme activity increased steadily, probably through dephosphorylation of latent reductase, the activation was largely complete at 48 h. During the steady state period of total reductase VLDL added to the medium at concentrations up to 50 microgram/ml protein had no effect o HMG-CoA reductase activity. In contrast, LDL suppressed the enzyme in a dose-dependent fashion to 40% of controls at 100 microgram/ml. On the other hand, HDL had the opposite effect with a significant induction up to 252% of controls at 50 microgram/ml. Insulin also caused a comparable dose-dependent stimulation of enzyme activity at 10(-8) and 10(-7)M, whereas glucagon inhibited reductase activity. Compared to the insulin action, triiodothyronine and triamcinolone prompted a minor, but still significant increase of reductase activity. Insulin and triamcinolone acted synergistically, but the combination of triamcinolone and tri-iodothyronine was only additive. All hormonal inductions of reductase could be blocked by cycloheximide. The present data establish that HMG-CoA reductase of maintenance cultured hepatocytes is subject to a complex regulation by heterologous lipoproteins as well as pancreatic, adrenal and thyroid hormones.

Adrenal Cortex Hormones↗

Binding and biological actions of insulin-like growth factors on human arterial smooth muscle cells.

Insulin-like growth factors (IGF) were isolated from human serum and compared with some biological actions of IGF supplied by Dr. J. Hapf, Zürich. Both factors were potent mitogens. They stimulated DNA-, RNA- and protein synthesis in cultivated human arterial smooth muscle cells. Furthermore, they enhanced the aminoacid transport. Our protein fraction (IGF Ulm) had a more potent biological activity than IGF (Zürich). Specific binding receptors for IGF (Zürich) on human arterial smooth muscle cells could be demonstrated. Specific binding of 125I-IGF (Zürich) was 10%. Half-maximal displacement was achieved by 250 ng/ml of unlabeled IGF (Zürich), by 1.2 micrograms/ml of IGF (Ulm), by 6.3 micrograms/ml of pro-insulin and by 17.8 micrograms/ml of insulin. In separate studies we could demonstrate that sera of normal adults, diabetic, acromegalic and hypophysectomized patients showed different growth-promoting activity in human arterial smooth muscle cells.

Acromegaly↗

Bile acid induced interconversion of 3-hydroxy-3-methylglutaryl Coenzyme A reductase in cultured intestine.

The effect of bile acids and bile acid/cholesterol micelles on 3-hydroxy-3-methylglutaryl coenzyme A reductase, the key enzyme of cholesterol synthesis, was investigated in cultured intestine. Glycocholic and glycodeoxycholic acid both suppressed total (fully activated) reductase activity after 3 h culture. The portion of expressed reductase, determined in the presence of NaF, was unaffected at 3 h, but decreased after 24 h of bile acid treatment. In contrast, total enzyme activity was stimulated up to 2.5-fold at 24 h; this bile acid effect was blocked by additional cholesterol. These results suggest that bile acids modulate both total reductase activity and the activation state of the enzyme in cultured intestine.

Animals↗