Search PubMed⌕ Search

Biomedical subjects

H Franke

Publications and source records attributed to H Franke.

At least 73 records · Page 4Linked to original sources
PubMed1990

[Fc-receptor mediated immune complex clearance function of the mononuclear phagocyte system in systemic lupus erythematosus].

Fc receptor mediated immune complex clearance function was measured in patients with systemic lupus erythematosus. Autologous erythrocytes were sensitized by human IgG anti-Rh(D) and used as immune complex model. An impaired Fc receptor function was demonstrable in 20 of 25 investigated patients. We have found a significant correlation between the seriousness of the defect and the step of the immunologic activity of the patients, but not between the impaired Fc receptor function and clinical activity and renal manifestation in our SLE patients. Further studies are necessary to determine the relevance of this phenomenon and to clear the possibility of therapeutical influence.

Adult↗
PubMed1989

Isolation and characterization of parenchymal cells from experimentally induced macronodular rat liver cirrhosis.

Hepatocytes were isolated from thioacetamide (TAA)-induced macronodular cirrhotic rat livers by a collagenase perfusion method. In the content of cellular metabolites, fatty acid uptake and lipid secretion there were no substantial differences compared with cells isolated from micronodular cirrhosis described previously. In contrast to isolated hepatocytes from normal livers those from macronodular cirrhosis had a lowered cellular content of triglycerides, phospholipids and cholesterol but not of cholesterol esters and free fatty acids. In macronodular cirrhosis hepatocytes of hypertrophic type, rich in cell organelles, can be distinguished ultrastructurally from those with signs of atrophy and degeneration. Immediately after isolation many hepatocytes isolated from macronodular cirrhosis showed plasma membrane blebbing. Whereas the blebbing was without recognizable effects on the fine structure of the isolated hepatocytes of the hypertrophic type, in the more atrophic ones some mitochondria were swollen. In addition, morphological analysis of the crude and purified suspensions revealed a partial selection of the hypertrophic cells during the isolation procedure, presumably due to a more labile state of those cells which showed signs of atrophy and degeneration. When stabilized in the suspension medium, however, the hepatocytes maintained complex metabolic functions for at least 2 h. Thus, the method described allows the isolation of parenchymal cells from TAA-induced macronodular cirrhotic livers for studying ultrastructural and biochemical alterations in hyperregenerative experimental liver cirrhosis.

Animals↗
PubMed1989

Hepatic actions of levonorgestrel: correlations between biochemical and morphological findings.

The influence of the synthetic sexual steroid levonorgestrel (LN) on rat liver in various doses and at different structural levels was investigated. A slight reactive hepatosis was found by histological examination after administration of LN in a dose of 10 mg per kg body wt. The same dose caused exclusively distinct lesions of the mitochondria, however, only in centrilobular parenchymal cells, whereas in the periportal hepatocytes only the lipid droplet content appears somewhat elevated. LN decreased the total glutathione content of the liver. The mitochondrial glutathione was decreased more intensively. One mg/kg body wt. of LN decreased the cytochrome P-450 content, but 10 mg/kg body wt. increased ethyl-morphine N-demethylation and 7-ethoxycoumarin O-deethylation activities. Distinct correlations could be shown between the biochemical changes and the ultrastructural findings.

Animals↗
PubMed1989

Glutathione synthesis and export in experimental liver cirrhosis induced by thioacetamide: relations to ultrastructural changes.

Micro-and macronodular experimental liver cirrhosis was induced in female rats by administration of 0.03% thioacetamide (TAA) in drinking water for 3 or 6 months, respectively. The glutathione (GSH) status (content, synthesis, export) and ultrastructural changes of liver were investigated 14 d after withdrawal of TAA. The hepatic level of GSH was increased after 6 months TAA treatment. The levels of oxidized glutathione (GSSG) were not changed after 3 months or 6 months TAA administration. The GSH synthesis was not disturbed in the cirrhotic livers; only the ratio between the 2 synthesizing enzymes was changed in macronodular liver cirrhosis. The plasma GSH content was reduced in both cases, independent of the stage of liver cirrhosis. The electron microscopic studies on cirrhotic rat livers revealed a series of characteristic structural changes, such as disorganization and total lack of the microvilli border, appearance of basement membrane-like deposits within the narrowed space of Disse, disappearance of the highly porous endothelial cell lining and partly an intensively detoriated blood supply within the pseudolobules. It is suggested that all these changes may contribute to a disturbance of the GSH export from the hepatocytes into the blood. It is very likely, however, that the alterations of the sinusoidal cell surface play the most important role. 1. The GSH/GSSG redox potential is shifted in favour of the reduced form in this cirrhosis model. This shift seems to be connected with later stages of cirrhogenesis. 2. A GSH export disturbance is responsible for the decreased plasma GSH level in liver cirrhosis.

Animals↗
PubMed1988

Receptor-mediated uptake of homologous low-density lipoproteins by isolated liver parenchymal cells of fetal rats.

The binding and uptake of gold-labeled homologous, apolipoprotein E-free low-density lipoproteins (LDL) by isolated fetal rat liver parenchymal cells in suspension were studied ultrastructurally and morphometrically. Binding experiments using 125I-labeled LDL were also performed. After a 2-h preincubation in a lipoprotein-free medium and a subsequent 1-h postincubation in the presence of LDL-gold, fetal liver parenchymal cells exhibit a binding of 248 +/- 17 gold conjugates/100 micron plasma membrane and an uptake of 235 +/- 17 gold conjugates/100 micron2 cytoplasm. Compared with values obtained from freshly isolated non-preincubated cells, these data correspond to a 15-fold and an 18-fold increase in total binding and uptake of LDL-gold, respectively. Competition experiments reveal that this increase is mainly a result of a 23-fold stimulation of specific binding and a 44-fold stimulation of receptor-mediated uptake of LDL-gold. The 125I-LDL binding experiments give a Kd value of 6.3 X 10(-8) M and a maximum binding capacity of 17.3 fmol LDL/10(6) cells. Our data provide evidence, further to our in vivo studies, that fetal rat liver parenchymal cells possess high-affinity binding sites for native homologous apolipoprotein E-free LDL. These sites may correspond to B, E receptors of adult rat liver parenchymal cells.

Animals↗
PubMed1988

Short-term effects of carbon tetrachloride on the lipoprotein secretion in isolated rat hepatocytes.

Short-term exposure of isolated rat hepatocytes in suspension to a low dose of CCl4 (20 micrograms/ml) leads within minutes to characteristic structural alterations. The earliest reaction is a disappearance of the microvilli border 5 min after starting the incubation. After 10 min the number of Golgi VLDL is decreased by about 80% and reaches zero after 20 min. The reduction in Golgi VLDL is associated with a decrease in the volume density of the Golgi complexes by about 50% compared with controls and by a marked elevation of intracytoplasmic and intralysosomal lipid deposits after 20 min incubation. Concomitantly with these alterations the total number of VLDL particles within single and multiple particle secretory vesicles located along the cell periphery decreases by about 50% 10 min after CCl4 exposure. This is followed 10 min later by a significant increase of about 20% compared with the corresponding controls. The elevation in the total number of VLDL is combined with an increase in the number of the multiple particle secretory vesicles. The particle content per vesicle, however; is significantly lower compared with controls. No reaction is detectable in the mitochondria, whereas the amount of RER appears to be decreased and that of the SER increased. The incubation of 14C-sodium palmitate prelabeled hepatocytes in the presence of CCl4 leads to a significantly higher content of labeled lipids in the total Golgi fraction and in the cytosol 20 min after CCl4 administration, whereas considerably less labeled lipids are secreted into the incubation medium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Relation between renal and hepatic excretion of drugs: VII. Hepatic and renal excretion of phenol red in thioacetamide-induced acute and chronic liver damage.

Acute and chronic liver damage was induced in rats by thioacetamide (TAA). Centrilobular liver cell damage associated with an accumulation of lipid droplets was produced by a single high dose (10 mg TAA/100 g b.m.). Liver fibrosis, micronodular and macronodular liver cirrhosis were induced by chronic TAA treatment (300 ml/l drinking water for 1.5, 3 or 6 months). Acute administration of TAA caused a significant decrease of hepatic phenol red excretion but no compensatory increase of its urinary excretion. In contrast, 24 h after bile duct ligation renal excretion of the dye increased by about 50%. After chronic exposure to TAA for three months hepatic phenol red excretion remained reduced and renal excretion raised significantly. This compensatory increase of urinary excreted phenol red amounts did not occur after 6 months of TAA treatment, probably as a result of additional nephrotoxicity of TAA. Two weeks after cessation of TAA exposure for 3 months, hepatic and renal phenol red excretion returned to normal. Bile flow per animal increased significantly after 3 months of TAA exposure. Apparently this is due to a reduced intrahepatic reabsorption of canalicular bile in TAA-damaged liver.

Animals↗
PubMed1988

Lack of detectable DNA alkylation for bromhexine in man.

It is known that in vitro incubation of the expectorant drug bromhexine (N-methyl-N-cyclohexyl-(2-amino-3,5-dibromobenzyl)-ammonium hydrochloride) with nitrite yields methylcyclohexyl nitrosamine (NMCA). NMCA is capable of methylating DNA when administered to rats. In vivo tests with bromhexine have also demonstrated that the drug methylates DNA when it is orally administered in the presence of sodium nitrite, presumably due to the intragastric formation of NMCA. In this study the potential of bromhexine to methylate nucleic acids in man, under physiological conditions, has been investigated. 20 volunteers were orally administered on each of three successive days 48 mg of bromhexine hydrochloride, labelled with three deuterium atoms in the N-methyl group. Urine was collected before treatment and subsequent to the last dose, and analysed by GC-MS for d0- and d3-7-methylguanine. 7-Methylguanine is naturally occurring in urine owing to the turnover of t-RNA of which it is a minor constituent. It is also a repair product from nucleic acids methylated by carcinogens, which is known to be excreted unmetabolised largely within 24 h of the methylation process. Unlabelled 7-methylguanine was present at levels of 7.36 +/- 2.43 mg/d in control urine and 6.12 +/- 2.36 mg/d in treated urine, in accord with previously published values. The excretion of isotopically labelled 7-methylguanine averaged 0.43 +/- 0.077% of the unlabelled concentration for control urines and 0.44 +/- 0.066% for treated urines, i.e. no d3-7-methylguanine could be detected following the drug treatment. The observed signals were largely accounted for by the naturally occurring isotopes 13C and 15N.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1988

Lack of detectable N-nitroso-N-methyl-N-cyclohexylamine in humans after administration of bromhexine.

The possible formation of N-nitroso-N-methyl-N-cyclohexylamine (NMCA) from the drug bromhexine (N-methyl-N-cyclohexyl-(2-amino-3,5-dibromobenzyl)-ammonium hydrochloride) and nitrite was investigated in humans using three different approaches: 1. analysis on metabolites of NMCA in human urine; 2. analysis on NMCA in human gastric juice; 3. in vitro incubation of human gastric juice with therapeutic bromhexine doses. Diet given to volunteers was varied during these investigations with respect to nitrate content. Experiments with a maximum load of 200 mg nitrate to stimulate nitrite formation were performed. Results of in vivo experiments did not indicate any formation of NMCA. In one out of 39 ex-vivo/in-vitro experiments (with a load of 100 mg nitrate in drinking water) 0.5 ng NMCA/ml gastric juice could be detected which is near the detection limit. Finally, this study showed that bromhexine is not secreted by saliva. This allows to conclude that nitrite and bromhexine do not reach the stomach simultaneously over a longer period of time. In consequence, medication with bromhexine is not regarded to represent a risk due to nitrosamine formation.

Bromhexine↗
PubMed1988

Rat LDL metabolism in the perinatal period.

In fetal rats at term LDL carries 75% of the total serum cholesterol, whereas in adult ones this value amounts to 20% only. Using a time-dependent two pool model the flux rates for LDL cholesterol can be calculated for the newborn. The data reveal that at birth the LDL cholesterol flux is 15-20 times higher than in the adult. During the first 2 h of postnatal life the FCR drops down from 0.4 at birth to values measured in the adult. Since at least 75% of LDL is of another origin than VLDL, a direct hepatic LDL synthesis is postulated for the newborn. The liver contributes to about 30% of the total LDL uptake which is mainly realized by a receptor-dependent mechanism, even though the fetus and the newborn exhibit markedly elevated LDL serum concentrations.

Animals↗
PubMed1987

Isolation and characterization of parenchymal cells from normal and cirrhotic rat liver.

A technique is described for isolation of adult rat hepatocytes from micronodular cirrhotic livers based on a collagenase digestion procedure. Hepatocytes from normal livers and those chronically injured by thioacetamide did not differ with respect to the viability measured by the trypan blue exclusion test or to the cellular concentrations of protein and glycogen, but the triglyceride content of cells from cirrhotic livers was significantly reduced. Hepatocytes isolated from cirrhotic livers are ultrastructurally in a good state of preservation but they appear to be poorer than controls in RER membranes, although the well-preserved mitochondria are somewhat richer in cristae. No differences were detected between the cell preparations in rates of gluconeogenesis and total de novo fatty acid synthesis, but the secretion of newly synthesized fatty acids was significantly reduced in cells from cirrhotic livers. Thus adult rat hepatocytes can be isolated from thioacetamide-induced micronodular cirrhotic livers with high yield and morphological integrity. Differentiated functions are maintained in suspension for at least 4 h.

Animals↗
PubMed1987

In vivo binding and uptake of low-density lipoprotein-gold- and albumin-gold conjugates by parenchymal and sinusoidal cells of the fetal rat liver.

To elucidate the participation of fetal rat liver cells in the receptor-mediated internalization of low-density lipoproteins (LDL), rat fetuses were injected with either LDL-gold or albumin-gold conjugates. The degree of binding and uptake of LDL-gold and albumin-gold by parenchymal and sinusoidal cells of the fetal rat liver differs markedly. Endothelial cells exhibit low LDL-gold uptake. In contrast, parenchymal cells internalize LDL-gold more actively (45 +/- 8 LDL conjugates/100 micrometers2 cytoplasm within 60 min). Kupffer cells exceed this value by a factor of 20. The uptake of albumin-gold by endothelial and Kupffer cells is high, whereas it is extremely low in parenchymal cells. Estradiol pretreatment causes a significant doubling (p less than 0.05) of the LDL-gold particle density/100 micrometers2 cytoplasm both in parenchymal and Kupffer cells, whereas estradiol has no effect on the albumin uptake. The results strongly indicate that LDL uptake by parenchymal and Kupffer cells in the fetal rat liver is mediated by estrogen-inducible receptors, which may correspond to B, E receptors in the adult liver.

Animals↗
PubMed1987

Pineal region tumours of childhood.

In Germany, the relative frequency of pineal region tumours seems to be much higher than hitherto assumed. At the University Hospital Hamburg, from 1980-1985 17 children with pineal region tumours were encountered amongst 102 children with CNS tumours. Two-cell-type germinoma is the most frequent pineal region tumour. Cerebrospinal fluid cytology is highly successful in identifying this germ cell tumour. Surgical removal has become a reasonably safe procedure in the treatment of pineal region tumours and was successful in all 10 cases so treated. In addition, our patients with two-cell-type germinomas received craniospinal axis radiation. All children, treated by both surgical removal and craniospinal axis radiation are so far relapse-free and are functioning on a pretreatment level.

Brain Neoplasms↗
PubMed1987

Clinical pharmacology of two specific bradycardiac agents.

The effect of two i.v.-infusion regimens of falipamil on atropine-induced changes of heart rate and the effect of ULFS 49 Cl in 3 different oral doses during a 7-day medication period were studied in volunteers. Both studies were double-blind, randomized and placebo controlled. Under placebo, low doses of atropine caused a 16% reduction in heart rate, a 1 mg cumulative dose increased heart rate by 23%. 100 mg falipamil was followed by a 9% reduction in heart rate. Low doses of atropine enhanced this decrease to 14%, whereas a 1 mg cumulative dose of atropine increased heart rate by only 3%. Similar results were obtained after administration of 200 mg falipamil. ULFS 49 Cl induced a constant reduction of heart rate at rest and during ergometry without changing systolic and diastolic blood pressure. Because no interrelation was found between efficacy and corresponding plasma levels of the drug, it can be concluded that the concentration of the drug in the tissue is responsible for efficacy and duration of action. The minimal effective and the therapeutic doses were 3 X 2.5 mg p.o. and 3 X 5 mg p.o. respectively. In contrast to falipamil, which increased the QT-interval by approximately 20%, ULFS 49 Cl did not change QT-time. Side-effects typical for 'specific bradycardic agents', such as coruscation were seen. Peak occurrence was between day 1 and day 4, thereafter a decreasing frequency was observed. In general, both drugs were effective and well tolerated.

Anti-Arrhythmia Agents↗
PubMed1987

[Cardiac arrhythmias in active elderly persons--age dependence of heart rate and arrhythmias].

Arrhythmias and heart rate of 82 active elderly persons (mean age 79.5 yrs) were registered by 24-hour electrocardiographic recording and compared with the results of 100 asymptomatic subjects (age 34.8 yrs). In each decade 10 men and 10 women were included. Maximal heart rate was lower in old age but over 100 bpm. Minimal and nocturnal heart rates showed a steady rise with increasing age. The mean 24-hour heart rate was higher in middle-aged females than in males, whereas in the elderly no sex-related difference was observed. Sinus arrhythmia, wandering pacemaker, short lengthening of RR-intervals prevailed in younger persons. Short sinus-tachycardias in the late night were equally frequent in both groups. The frequency of supraventricular premature beats did not differ between the two groups (85.4 vs. 76%). However, high intraindividual numbers and more complex forms were more frequent in the elderly. Paroxysmal atrial fibrillation was never registered. Permanent atrial fibrillation occurred in 41% of the subjects being between 90 and 102 years of age. Ventricular arrhythmias were age-related: 87.2% of the elderly vs. 50% of the middle-age subjects had ventricular premature beats, predominantly frequent and complex forms. A significant age relation to bradycardias could not be observed: Sinus pauses over 2000 ms (11 vs. 17%), first and second degree AV-block (22 vs. 21%) occurred equally frequent in both groups. An intermittent short third degree AV-block was observed in a man 84 years old who was asymptomatic. Right bundle branch block was present only in the elderly (6.1%). No arrhythmia-related increase of mortality was observed during a seven-year follow-up.

Aged↗