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Biomedical subjects

H Köhler

Publications and source records attributed to H Köhler.

At least 289 records · Page 16Linked to original sources

Cyclosporin A-binding protein (cyclophilin) of Neurospora crassa. One gene codes for both the cytosolic and mitochondrial forms.

Cyclophilin (cyclosporin A-binding protein) has a dual localization in the mitochondria and in the cytosol of Neurospora crassa. The two forms are encoded by a single gene which is transcribed into mRNAs having different lengths and 5' termini (approximately 1 and 0.8 kilobases). The shorter mRNA specifies the cytosolic protein consisting of 179 amino acids. The longer mRNA is translated into a precursor polypeptide with an amino-terminal extension of 44 amino acids which is cleaved in two steps upon entry into the mitochondrial matrix. Neurospora cyclophilin shows about 60% sequence homology to human and bovine cyclophilins.

Amino Acid Sequence↗

[Secondary immune deficiency in renal failure exemplified by hepatitis B vaccination].

In dialysis patients the immune response to hepatitis B-vaccination is greatly impaired. In vitro the non-responders show a failure of the monocytes to support the process of primary T-cell activation. This defect results in a lack of interleukin 2-production and an enhanced sensitivity of the interleukin-2 receptor system. Addition of low doses of interleukin-2 fully reconstitutes the deficient immune response in vitro. Furthermore, the local application of low dose interleukin-2 during a standard vaccination with 40 micrograms hepatitis B-vaccine normalizes the non-responder state in vivo.

Hepatitis B↗

[The significance of inflammatory vascular diseases].

Out of the from angiological points of view most important inflammatory vascular diseases (obliterating endangiitis, giant cell arteriitis, Takayasu's disease) epidemiological data are compiled. Remarkable is the increasing part of female patients in endangiitis. Furthermore it is referred to the particular functional situation in these vascular diseases, which results from the localisation of a peripheral occlusion, insufficient formation of collaterals or disturbed rheology.

Aortic Arch Syndromes↗

[Serum magnesium and heart arrhythmias in patients with pelvic-leg arteriosclerosis].

In 122 male patients with arteriosclerosis of pelvis and legs up to 5 resting electrocardiograms were registered in the course of 4 years. 5.2% of these electrocardiograms showed disturbances of rhythm. In these cases no significant differences in the serum magnesium level could be ascertained between patients with and without disturbances of rhythm.

Arrhythmias, Cardiac↗

[Initial experiences with the effect of chronic intermittent electromyostimulation in patients with hyperlipoproteinemias and arterial circulatory disorders].

Metabolic and clinical effects of an original electromyostimulation are explained which induces muscle contractions by changes of the field intensity in the region of microseconds in forms of delivered impulse groups. On account of the good local compatibility due to optimal irritation parameters the muscle stimulator was suitable for a long-term application. Examinations on 23 patients with hyperlipoproteinaemia and mixed HLP (n = 15) and primary hypercholesterolaemia (n = 8) after a 2 times 2 hours/day mutual stimulation of the femoral musculature in a frequency of 2 s-1 lasting four weeks yielded a significant decrease of the triglyceride and cholesterol concentrations as well as an increase of the HDL-cholesterol in mixed HLP-forms. Examinations not yet finished refer to an increase of the extrahepatic activity of the postheparin-lipoprotein lipase and to the concentration of the HDL2-cholesterol. An influence of the hypercholesterolaemia IIa could not be made evident. An electrostimulation performed for 3 months in 8 patients with obliterating arteriosclerosis resulted in a more sufficient collateral blood supply of the legs. The long-term use of the device was unobjectionable also under ambulatory conditions. On the basis of additionally gathered experiences further indications of an electrostimulation were cited. Possible variations of the electrostimulation irritation parameters might make accessible further fields for the preventive and curative medicine.

Adult↗

IgG subclass distribution of autoantibodies to glomerular basement membrane in Goodpasture's syndrome compared to other autoantibodies.

The IgG subclass distribution of autoantibodies to glomerular basement membrane (anti-GBM antibodies) was investigated and compared to the distribution of liver-kidney microsomal (LKM) autoantibodies in chronic active hepatitis, to antimitochondrial autoantibodies (AMA) in primary biliary cirrhosis, and to the subclass distribution of total serum IgG within a healthy population. Solid phase assays for the demonstration of these autoantibodies were performed with four mouse monoclonal antibodies specific for each human subclass to provide quantitative data for the autoantibodies. In addition, the subclass distribution of total IgG in these sera was analyzed. IgG1 accounted for 75% of the total antibody activity in anti-GBM antibodies. In LKM antibodies a more homogeneous distribution was observed between the different subclasses with a relative high proportion of IgG4 autoantibodies (21.2%). In AMA a high proportion of IgG3 subclass autoantibodies was found (anti-p-48 = 28.7%, anti-p-62 = 29.9%). In these patients a high proportion of IgG3 (23 vs. 27.2%) could also be demonstrated in the subclass distribution of total IgG, whereas in patients with anti-GBM antibodies and LKM antibodies the subclass distribution of total IgG was comparable to a population of healthy volunteers. We conclude that the subclass distribution in anti-GBM antibodies differs from the distribution in other autoimmune diseases and from a healthy population and that these differences may be of pathogenetic relevance.

Anti-Glomerular Basement Membrane Disease↗

Vagal influence on cholecystokinin and neurotensin release in conscious dogs.

Cholecystokinin (CCK) release in seven conscious dogs was investigated by means of modified sham feeding. After sham feeding mean CCK concentrations rose from a basal value of 1.0 +/- 0.2 pmol/l to a peak value of 2.4 +/- 0.3 pmol/l (p less than 0.005). The release in response to sham feeding amounted to half of that seen after normal feeding. Atropine significantly altered CCK output after sham feeding (basal, 1.0 +/- 0.2 pmol/l; peak 1.3 +/- 0.3 pmol/l). Sham feeding did not affect neurotensin release. It is concluded that an important cephalic phase of CCK release exists which seems to be dependent on a cholinergic mechanism.

Animals↗

Immunological properties of the human Goodpasture target antigen.

The globular domain NC1 of human basement membrane collagen IV was isolated from glomerular basement membrane after collagenase digestion by chromatographic purification. The human NC1 appears as a hexamer of 160 kD by molecular sieve chromatography which migrates as a single molecule at gel electrophoresis without sodium dodecyl sulphate (SDS). Reversible dissociation of the hexamer into monomers and dimers was achieved by 6 M guanidine-HC1, SDS, or at pH values less than 4.0. All the subunits of 26 kD, 28 kD, 44 kD, and 50 kD showed reactivity with anti-GBM antibodies on immunoblotting. Inhibition-ELISA demonstrated that the intact hexamer also binds to anti-GBM antibodies at higher NC1 concentrations. However, dose-response curves indicated an approximately 20-50-fold increase in reactivity after dissociation of the hexamer in 6 M guanidine-HC1. Analysis of thermostability demonstrated that heating for 24 h at 37 degrees C or 56 degrees C did not alter the reactivity to anti-GBM antibodies, while reactivity was lost after heating for more than 120 min at 95 degrees C. In contrast to bovine NC1 unfolding of the antigen occurs immediately and does not require elevated temperature. Rotary shadowing of human NC1 at neutral pH revealed homogeneous globules. Distinct but incomplete dissociation into monomers and dimers could be observed at pH 2.5. These in vitro data of the human NC1 domain give further evidence that most of the Goodpasture epitopes are sequestered within the NC1 hexamer and support the hypothesis that production of anti-GBM autoantibodies may be initiated after dissociation of the hexamer has been induced, possibly by a toxic or infective episode.

Adult↗

Import of cytochrome c into mitochondria. Cytochrome c heme lyase.

The import of cytochrome c into mitochondria can be resolved into a number of discrete steps. Here we report on the covalent attachment of heme to apocytochrome c by the enzyme cytochrome c heme lyase in mitochondria from Neurospora crassa. A new method was developed to measure directly the linkage of heme to apocytochrome c. This method is independent of conformational changes in the protein accompanying heme attachment. Tryptic peptides of [35S]cysteine-labelled apocytochrome c, and of enzymatically formed holocytochrome c, were resolved by reverse-phase HPLC. The cysteine-containing peptide to which heme was attached eluted later than the corresponding peptide from apocytochrome c and could be quantified by counting 35S radioactivity as a measure of holocytochrome c formation. Using this procedure, the covalent attachment of heme to apocytochrome c, which is dependent on the enzyme cytochrome c heme lyase, could be measured. Activity required heme (as hemin) and could be reversibly inhibited by the analogue deuterohemin. Holocytochrome c formation was stimulated 5--10-fold by NADH greater than NADPH greater than glutathione and was independent of a potential across the inner mitochondrial membrane. NADH was not required for the binding of apocytochrome c to mitochondria and was not involved in the reduction of the cysteine thiols prior to heme attachment. Holocytochrome c formation was also dependent on a cytosolic factor that was necessary for the heme attaching step of cytochrome c import. The factor was a heat-stable, protease-insensitive, low-molecular-mass component of unknown function. Cytochrome c heme lyase appeared to be a soluble protein located in the mitochondrial intermembrane space and was distinct from the previously identified apocytochrome c binding protein having a similar location. A model is presented in which the covalent attachment of heme by cytochrome c heme lyase also plays an essential role in the import pathway of cytochrome c.

Chromatography, High Pressure Liquid↗

Studies on the regulation of enolases and compartmentation of cytosolic enzymes in Saccharomyces cerevisiae.

Three enolase isoenzymes can be distinguished after electrophoresis of yeast crude extracts. After adding glucose to derepressed cells, there was a coordinated increase in the activity of enolase I and decrease in enolase II activity. Enolase I was found to be repressed and enolase II simultaneously induced by glucose. The third enolase activity remained unchanged and was identified as that of a hybrid enzyme. Enolase catalyses the first common step of glycolysis and gluconeogenesis. Gluconeogenic enolase I shows substrate inhibition for 2-phosphoglycerate (glycolytic substrate) and glycolytic enolase II is substrate-inhibited by phosphoenolpyruvate (gluconeogenic substrate). The gluconeogenic reaction was inhibited up to 45% by physiological concentrations of fructose 1,6-bisphosphate. To test for cytological compartmentation, a method was developed for isolating microsomes. Effective enrichment of rough and smooth endoplasmic reticulum was demonstrated by electron microscopy. No evidence was obtained for any compartmentation of either enolases or other glycolytic enzymes.

Carbon↗

Surgical treatment of pancreatic pseudocysts.

Between 1966 and 1980, 54 patients (40 men and 14 women) with a mean age of 38 years were operated on for a pancreatic pseudocyst at the Department of General Surgery, University of Göttingen. The aetiology of the cysts was alcohol abuse in 35 patients, biliary diseases in 8, blunt abdominal trauma in 4, virus-induced in 2 and unknown in 5. With the exception of those who had had trauma, all patients were suffering from chronic pancreatitis. Surgical therapy included in all cases a cystojejunostomy (52 with a Roux-Y-limb and 2 with an omega loop). The mean follow-up period was 13 years (range 6 to 20 years). The late mortality was 15 per cent (8 of 52 patients). Recurrent cysts occurred in two patients (5 per cent) and relapse of pancreatitis in one third of the patients. Deterioration of carbohydrate metabolism was observed in 20 per cent of the patients. After drainage operation stool fat content became normal in 20 per cent and deteriorated in 13 per cent. Persistence or cessation of alcohol intake influenced the long-term results. From these data we conclude that both alcohol withdrawal and sufficient drainage of the pseudocyst are important factors in the prognosis of pseudocyst.

Adult↗

Acute pancreatitis and hyperamylasaemia in pancreatic carcinoma.

To determine the incidence of acute pancreatitis in pancreatic carcinoma, a retrospective study was performed in 174 patients. Acute pancreatitis was found in 24 (13.8%), and hyperamylasaemia, but no clinical manifestation of acute pancreatitis, was found in 17 (9.8%) of these patients. The incidence of acute pancreatitis was higher when the papilla of Vater or the head of the pancreas was involved. Clinically, pancreatitis was slight to moderate, and the underlying disease was soon diagnosed with invasive procedures. Pancreatic carcinoma should be considered an etiological factor in patients with relapsing and/or unexplained pancreatitis of long duration.

Acute Disease↗