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Biomedical subjects

H Franke

Publications and source records attributed to H Franke.

At least 91 records · Page 5Linked to original sources

Binding and internalization of low density lipoproteins in fetal rat liver at term under in vivo and in vitro conditions.

Binding and internalization of rat low density lipoproteins (LDL) by fetal rat liver cells were studied under in vivo and in vitro conditions by ultrastructural and biochemical methods. By using LDL-gold conjugates it could be shown that on day 22 of gestation hepatocytes and Kupffer cells mainly contribute to specific binding and uptake of LDL, but not endothelial cells. Estrogen administration to the pregnant rats stimulated binding and internalization of LDL-gold. The binding characteristics of isolated fetal hepatocytes were determined by 125I-LDL. The data allow the conclusion that fetal hepatocytes and Kupffer cells possess specific B/E receptors.

Animals↗

A post-embedding immunoelectron-microscopic demonstration of apolipoprotein-B-containing lipoprotein particles in hepatocytes of fetal rats.

We used the protein-A gold technique to demonstrate the presence of apolipoprotein-B in ultrathin sections of fetal rat liver tissue. It was possible to show for the first time that the electron-dense, osmiophilic particles with diameters of 20-40 nm located within the RER cisternae and Golgi complexes of fetal rat hepatocytes contain apolipoprotein-B components and therefore are lipoproteins. After specific labelling an accumulation of gold label was observed on the RER cisternae, Golgi cisternae and the Golgi-associated secretory vesicles of hepatocytes. The specificity of this labelling pattern was assessed by comparison with cytochemical controls. Our qualitative findings were confirmed by a quantitative analysis of the mean labelling intensity (mean number of gold particles per square micron of the surface area of a particular cellular compartment) on the RER, Golgi complexes, mitochondria, nuclei and the remaining cytoplasm of hepatocytes. It is concluded that the hepatocytes of fetal rats are capable of forming apolipoprotein-B-containing lipoprotein particles. With respect to the size-distribution pattern of the observed intra-hepatic lipoprotein particles, we suggest that the hepatocytes of fetal rats produce lipoproteins of the low- and very low-density-lipoprotein type.

Animals↗

Studies on lipid and lipoprotein metabolism in rat liver cirrhosis induced by different regimens of thioacetamide administration.

In female Wistar rats the animal model of TAA-induced liver cirrhosis has been tested for reliability and usefulness for studies on lipid and lipoprotein metabolism in cirrhosis. From our results we draw the following conclusions: Application of 300 mg TAA/l drinking water from the 4th to the 6th month of life leads in all treated rats to liver cirrhosis which is rather uniformly of micronodular surface morphology. Under this treatment the survival rate is about 90 percent. Increasing the administered dose (450 and 600 mg/l) and/or extension of TAA administration time (4 or more months) leads to decreasing survival rates, and to a shift from micronodular towards macronodular cirrhosis. To produce macronodular cirrhosis it is suggested to extent the application time rather than to increase the dose since in the latter case the survival rate is very low. The alterations of lipid and lipoprotein metabolism observed in this animal model, i.e. decrease of pre-beta-lipoproteins, increase of beta-lipoproteins, decrease of serum triglyceride concentration and decrease of hepatic VLDL-TG output into the serum are in good agreement with those observed in human cirrhosis. Thus, the TAA-induced chronic liver injury proved to be a reliable and useful model for studies on lipid and lipoprotein metabolism in liver cirrhosis.

Acetamides↗

Morphometric studies on lipoprotein particles in developing rat liver and their corticosteroid-induced changes during the late gestational period.

Changes in lipoprotein particles in hepatocytes of the fetal rat liver have been studied morphometrically from days 15-21 of gestation. On all these days, distinct lipoprotein particles are found within the cisternae of the RER, Golgi complexes and Golgi-derived secretory vesicles. Their mean diameter is 30-31 nm. The number of Golgi complexes per hepatocyte, the lipoprotein particle number per Golgi complex and the volume density of the latter remain unchanged within the developmental period examined. The volume density of lipid droplets, however, shows a significant decrease during this time. Following corticosteroid treatment, the mean diameter of lipoprotein particles, the number of lipoprotein particles per Golgi complex, the volume density of the Golgi complex, and that of the lipid droplets increase significantly within the examined period, whereas the number of Golgi complexes per hepatocyte is reduced. These data support the view that triglyceride production in the fetal liver is directly or indirectly stimulated by corticosteroids administered to the pregnant rat, thus giving rise to larger amounts of hepatic lipoproteins and lipids.

Animals↗

Changes in intra- and extrahepatic VLDL in the rat following acute injury by thioacetamide. A morphometric and biochemical study.

The effect of a single dose of TAA (100 mg/kg body weight) on intra- and extrahepatic lipoproteins of the very low density (VLDL) type was studied in rats by morphometric and biochemical methods. For a better quantification of VLDL in the periportal (zone 1) and centrilobular (zone 3) hepatocytes of control and TAA-intoxicated livers, colchicine was used as an inhibitor of hepatic lipoprotein secretion. Generally, there exists a great functional heterogeneity between the hepatocytes of zone 1 and 3 in the colchicine-treated controls manifested in a significantly different accumulation rate of VLDL particles. The mean number of VLDL particles per vesicle, the mean secretory vesicle size and the volume density of the electron-lucent secretory vesicles are two times larger in hepatocytes of zone 1 than zone 3. The volume of the VLDL particles amounts to 7.3 X 10(-5) microns3 and 22 X 10(-5) microns3 in the peri- and centrilobular regions. On the other hand, there is no significant lobular-zonal difference in the number of light and dark secretory vesicles. Within 48 h TAA treatment causes a reduction in the number of VLDL particles/100 microns 2 in zone 1 and 3 by 66% and 61%, whereas the number of light secretory vesicles is decreased by 31% and 58%, respectively. The volume density of the latter is significantly diminished only in zone 1. Moreover, the VLDL particle volume is reduced to nearly 50% in each lobular zone examined. The data obtained after TAA treatment from the electron-dense secretory vesicles do not differ significantly from those of the colchicine-treated controls. Acute TAA intoxication lowers the hepatic VLDL-TG output by about 50% in comparison with controls. The steady state of the serum TG concentration after TAA application implies that the clearance of TG from the serum must be diminished to the same extent as the hepatic TG output is found to decrease due to acute liver injury. The results presented here support our view that acute TAA intoxication lowers the hepatic VLDL output by inhibiting the intracellular formation of VLDL. The intrahepatic degradation of the newly synthesized VLDL seems to be unaffected. Despite the fact that the substructure of the hepatocytes in zone 3 is much more changed than in zone 1 after TAA treatment the quantitative data on the VLDL secretory products provide evidence that the process of lipoprotein formation is disturbed to nearly the same extent by TAA both in zone 1 and 3.

Acetamides↗

Biochemical and substructural studies on hepatic and serum lipoprotein metabolism after acute liver injury induced by thioacetamide in rats.

The effect of an acute liver injury induced by thioacetamide (TAA) on hepatic and serum lipoprotein metabolism in rats was studied using biochemical and ultrastructural methods. A single dose of 100 mg TAA/kg body weight caused within 48 h a decrease of hepatic triglyceride (TG) output into the serum by about 50% in comparison to the controls. The steady state of serum TG concentration from 24 to 96 h after TAA treatment implies that the clearance of TG from serum must be diminished to the same extent as the hepatic TG output was found to decrease. Moreover, the TAA treatment caused changes in the electrophoretic mobility as well as in the concentration and composition of circulating serum-lipoproteins. The electrophoresis revealed a decrease in the alpha-band, which can be explained by the decrease in the high density lipoproteins (HDL) total lipid concentration. The pre-beta-migrating band disappeared, whereas a broad beta-mobility band appeared, which most likely consists of a mixture of very low density lipoproteins (VLDL) and low density lipoproteins (LDL) as can be concluded from the changes in concentration and composition of lipids in both fractions. For a better visualization of the VLDL-forming capability in perilobular and centrolobular liver parenchymal cells of the TAA-treated animals the VLDL secretion blocking agent colchicine was used. It was shown that in comparison with colchicine-treated controls the VLDL secretory products are accumulated at a considerably lower rate manifested in a diminution of VLDL clusters, secretory vesicle size and the number of intravesicular VLDL particles.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetamides↗

[Cardiovascular findings in patients over 100].

General (1) and specific (2) behaviour of the cardiovascular system were investigated in 575 persons with a documented age of over 100 years. In 118 over-100-year-olds the arterial blood pressure was within normal limits. Extremely old age is compatible with a variety of disturbances of cardiac impulse formation and propagation. This does not include malignant third-degree atrioventricular block. The pattern of serum lipoproteins was studied in 20 long-lived persons and showed a favourable atheromatous index. The width of the abdominal aorta was determined by ultrasound and was close to the value found in 60-year-olds. Specific cardiovascular findings clearly depend on the vitality of the over-100-year-olds. Fully active centenarians (group I, n = 169), despite cardiological polypathy, have a well compensated cardiovascular system. Three coronary angiograms performed post mortem showed coronary sclerosis in all cases but only moderate coronary stenosis. Approximately 50% of the centenarians belonging in group II, i.e., those not so active or even slightly disabled (n = 275) and all members of group III (bedridden, n = 131) show latent or manifest cardiac decompensation.

Age Factors↗

[Morphometric mitochondrial studies in the placenta of early pregnancies following a normal course of pregnancy and in maternal diabetes mellitus].

89 electron micrographs from a diabetic placenta of the 8th week of pregnancy and from two normal placentas of the same period of gestation are investigated morphometrically. In the trophoblast mitochondria of the diabetic placenta the surface/volume ratio between the surface of the cristae and mitochondrial volume shows a statistically significant reduction as compared to the values in the normal placenta of the same period of gestation. The morphological changes of the placenta are being related to disorders of the regulation of the metabolic processes in diabetes mellitus in early pregnancy.

Blood Glucose↗

Effect of diuretics on the tubuloglomerular feedback response.

To study the influence of diuretics on the tubuloglomerular feedback mechanism, early proximal stop-flow pressure (SFP) was measured during loop exposure to different drug concentrations. SFP was recorded continuously during arrested flow and at a perfusion rate of 50 nL/min. The perfusate consisted of isotonic saline, to which varying amounts of furosemide. bumetanide, piretanide, or hydrochlorothiazide were added to obtain final concentrations between 10(-6) and 10(-4)M. The loop diuretics furosemide, bumetanide, and piretanide showed inhibition: an inverse log-linear relation between the luminal concentration and the respective feedback response. No differences between the dose-response curves of furosemide, bumetanide, or piretanide could be demonstrated. The effective concentration range was between 10(-6) and 10(-4)M, the mean effective dose (ED50) was close to 10(-5)M for each of them. In contrast, hydrochlorothiazide did not alter the feedback response. The effect of loop diuretics was rapidly and repeatedly reversible.

Animals↗

A simple method for the isolation of highly enriched hormone-sensitive parenchymal liver cells from fetal rats.

A well reproducible method for preparing isolated parenchymal cells from fetal rat liver on the 22nd day of gestation by tryptic digestion is described including criteria for assessing their viability. The content of parenchymal liver cells was higher than 90% as could be demonstrated by light microscopic analysis of thin sections of the pelleted hepatocytes. Electron microscopic examination of the freshly prepared suspension revealed a well preserved ultrastructure of the hepatocytes. The metabolic competence of the isolated fetal hepatocytes was tested by alpha- and beta-adrenergic stimulation of glycogenolysis and glycogenolytic glucose release.

Animals↗

[Hypothyroidism in the elderly of advanced age].

Thyroid function tests were performed on 445 in-patients over a four month period at the Department of Medicine of a teaching hospital attached to the University of Kiel. Excluding those severely ill, moribund or known to have abnormal thyroid function, the study included all patients over 60 years of age. Diagnostic criteria were clinical symptoms, results of the TRH test and of T4-RIA, in addition to nonspecific tests of blood sugar, serum cholesterol and blood count. Among the 445 patients there were 15 with manifest hypothyroidism (3.4%), previously undiagnosed. A further 23 (5.2%) had the subclinical variant of "borderline hypothyroidism". The sex ratio was normal for manifest and for borderline hypothyroidism. The classical cardinal clinical symptoms were present in only those with severe and marked hypothyroidism, i.e. not even a third of all those with manifest hypothyroidism.

Aged↗