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G Hübner

Publications and source records attributed to G Hübner.

At least 127 records · Page 7Linked to original sources
PubMed1986

Activation of mitochondrial ATPase as evidence of loosely coupled oxidative phosphorylation in various skeletal muscle disorders. A histochemical fine-structural study.

Combined histochemical and biochemical studies have shown, that the histochemical activity of mitochondrial Mg2+-activated ATPase closely correlates with the coupling state of oxidative phosphorylation (Meijer and Vloedman 1980). Using this histochemical method 646 unselected skeletal muscle biopsies have been investigated. Activation of the enzyme, i.e. loosely coupled mitochondria were present either focally or diffusely expressed in 28% of the biopsies irrespective of the underlying disorder. Most often it was found in mitochondrial myopathies and in progressive muscular dystrophy type Duchenne; in a lesser degree it was also present in neurogenic atrophy and in various other disorders. Ninety two percent of all cases with loose coupling showed mitochondrial proliferations. On the other hand in 20% of all cases with mitochondrial proliferations including 19 cases of diffuse mitochondrial myopathy and 3 of progressive external ophthalmoplegia no activation of the enzyme was found. The results show that loose coupling is closely but not absolutely associated with mitochondrial proliferation, it is present in mitochondrial myopathies but also in various other muscular disorders with different pathogenesis.

Adenosine Triphosphatases↗
PubMed1986

Investigations on the pyruvate decarboxylase catalysed oxidative decarboxylation of 2-oxoacids by 2.6-dichlorophenolindophenol.

Pyruvate decarboxylase, a thiamine pyrophosphate and Mg2+ dependent enzyme, catalyzes normally the simple decarboxylation of its substrate. However, in the presence of suitable hydrogen acceptors, such as dichlorophenolindophenol, it catalyzes an artificial reaction, the oxidative decarboxylation of 2-oxoacids to the corresponding carboxylic acids. As a result of kinetic studies a mechanism is presented in this paper, which describes the synchronous progress of both the oxidative ping-pong-type decarboxylation reaction and the physiological non-oxidative decarboxylation reaction. Moreover, experiments using phenylglyoxylic acids that carry suitable substituents in the 4-position have shown that the electronic influence of the substituents (causing a decrease in the rate constants with increasing electron pressure) is in quantitative agreement for both types of reactions. A common rate limiting transition state preceding the alpha-carbanion intermediate of the enzymic reaction (2-(1-hydroxybenzyl)-thiamine pyrophosphate carbanion) must therefore be assumed for both reactions. Acetaldehyde which acts as noncompetitive inhibitor in the normal enzyme mechanism does not influence the oxidative decarboxylation reaction. 4'-hydroxy-4'-deamino-thiamine pyrophosphate is inactive as coenzyme for both types of enzyme reactions. This confirms again the essential role of the 4'-amino group in the cofactor function.

2,6-Dichloroindophenol↗
PubMed1986

Determination of antibodies to rubella virus with the disperse dye immunoassay (DIA) in comparison with an enzyme-linked immunosorbent assay (ELISA).

A disperse dye immunoassay (DIA) using Fantagen-dye sol particles as label was developed for the measurement of rubella antibodies in human serum specimen. The DIA has a sensitivity comparable to the hemagglutination-inhibition (HI) test, whereas the detection limit for a similar ELISA-system developed in parallel is lower by a factor of about two orders of magnitude. The results of testing 34 random serum specimens with the 3 different methods showed a significant correlation (v = 0.73 for DIA vs. ELISA). Titer rises in 10 paired sera (acute/convalescent) estimated with the DIA- and ELISA-methods were in good agreement with H1-results. Only two of the 10 pairs differed in titer rise by no more than one dilution step.

Antibodies, Viral↗
PubMed1985

Fibromatosis hyalinica multiplex (juvenile hyalin fibromatosis). Light microscopic, electron microscopic, immunohistochemical, and biochemical findings.

Fibromatosis hyalinica multiplex juvenilis (juvenile hyalin fibromatosis) is a very rare mesenchymal dysplasia, probably inherited as an autosomal-recessive trait. Two nonrelated cases are reported. Among the clinical features, the most impressive lesions are multiple slowly growing subcutaneous nodules, hypertrophic gingiva, flexural contractures with joint stiffness and radiolucent bone destructions. Light microscopic examination of the nodules reveals tumor-like deposits of an amorphous hyaline ground substance with delicate staining properties situated partly between cellular and vascular areas. Ultrastructural characteristics are cystic, dilated rough endoplasmatic reticulum and cystic Golgi vesicles which contain a fine fibrillar material that is also found in the ground substance. Immunohistochemical examination shows collagen type I and type III in the hyaline material, but not type II and type IV. Quantitative biochemical investigation reveals a normal ratio of collagen types I and III.

Adolescent↗
PubMed1985

Mitochondrial myopathy with diffuse activation and focal deficiency of mitochondrial ATPase and carnitine deficiency.

In skeletal muscle from a patient with a mitochondrial myopathy and muscular carnitine deficiency, histochemical analysis demonstrated that mitochondrial ATPase showed activation with loss of latency even before addition of the uncoupler dinitrophenol (DNP). According to combined histochemical and biochemical studies by Meijer and Vloedman (1980), this finding indicates loosely coupled oxidative phosphorylation. After the addition of DNP the reaction intensity was markedly increased, but there were scattered enzyme-deficient fibres in which some residual activity was shown by ultracytochemistry. No defect in mitochondrial enzymes was found in biochemical studies. The enzyme histochemical changes and carnitine deficiency are probably both secondary to an unknown mitochondrial defect. Both the carnitine deficiency and the mitochondrial myopathy remained unchanged following long-term carnitine substitution therapy despite clinical improvement.

Adenosine Triphosphatases↗
PubMed1985

Distribution of 125I-thyroxine in different organs and tissues of dietically obese rats.

The distribution of 125I-thyroxine (% dose/g tissue; tissue/plasma radioactivity ratio) was investigated in different tissues of 28-week-old obese Wistar rats. Obesity was induced by high-fat diet (HFD) and confirmed by carcass analysis; in heavy obese animals the relative and absolute fat content is increased twofold and threefold, respectively, compared to control rats fed on a low-fat diet (LFD). Heavy HFD rats exhibit diminished 125I-T4 distribution in the "slow pool" (fat tissue, muscle) and unchanged values in the "fast pool" (liver, kidney) in comparison with LFD rats with low body weight. The differences in distribution presented here are not caused by the diet per se, but they are the consequence of the obesity of the animal, because no differences in the 125I-T4 distribution were found in the 125I-T4 between HFD and LFD rats with relatively equal body weight and body composition. The reduced T4 distribution in the fat tissue of obese rats is discussed in connection with possibly decreased lipolysis in this tissue and possible causal participation in the beginning of obesity.

Adipose Tissue↗
PubMed1984

[Diagnostic significance of muscle biopsies in metabolic myopathies. II. Clinical biochemistry].

In the diagnosis of metabolic myopathies the use of biochemical methods, in addition to morphological examination of muscle biopsies, is often necessary in order to identify a specific metabolic defect. In order to narrow down the spectrum of biochemical methods, extensive clinical investigation and morphological examination, including histology, enzyme histochemistry and electromicroscopy if necessary have to be done beforehand. Patients are classified in the following groups: 1) progressive muscular weakness and/or muscle wasting with storage of a) glycogen, b) lipid or c) mitochondrial alterations; 2) recurrent rhabdomyolysis induced by fasting or exercise a) with glycogen storage or b) without any specific morphological alterations. The spectrum of metabolic defects comprises disorders of glycogen and glucose metabolism (deficiency of acid maltase, debranching and branching enzyme, phosphorylase, phosphofructokinase and other glycolytic enzymes), lipid metabolism (carnitine deficiency, carnitine palmitoyl transferase deficiency), mitochondria (respiratory chain disorders, pyruvate dehydrogenase deficiency) and others such as adenylate deaminase deficiency. In some of these e.g. infantile acid maltase deficiency and mitochondriopathies, it is clinically more important when organs other than muscle are affected; however, muscle biopsy is a useful substrate for diagnosis of these metabolic disorders.

Adult↗
PubMed1984

[Diagnostic significance of muscle biopsies in metabolic myopathies. I. Myopathology].

The clinical course of metabolic myopathies is dominated by progressive muscle weakness and wasting or aching contraction and recurrent rhabdomyolysis with intense exercise. Vacuolar muscle fibre degeneration is the leading pathological finding on routine histological examination. For further characterization of those histologically empty looking vacuoles, histochemistry and electron microscopy are employed. Increase of glycogen, lipid droplets or mitochondria can often be demonstrated and indicate the need for subsequent biochemical identification of the underlying metabolic defect. Some other metabolic myopathies that cause recurrent rhabdomyolysis lack myopathological abnormalities. These can only be diagnosed biochemically, but additional new histochemical screening methods might be helpful.

Biopsy↗
PubMed1984

[Adult form of acid maltase deficiency presenting as progressive spinal muscular atrophy].

As far as could be elucidated, a sporadic manifestation of a slowly progressing muscular weakness and atrophy had commenced in a female patient symmetrically in the pelvic girdle and thigh region at the age of about 22 years. Only at the age of 55 years a precise neurological examination was done. On the basis of clinical and electromyographic data spinal muscular atrophy of the Kugelberg-Welander type was diagnosed. Muscular biopsy demonstrated severe far-progressed neurogenic muscular atrophy. In addition, increased storage of PAS-positive material was noticed. This was particularly true in the sparsely preserved, non-denervated muscular areas changed in the manner of an accompanying myopathy. Complementing electron microscopy and pathobiochemistry in the muscular biopsy showed an adult form of lack of acid maltase (Pompe's disease) aetiologically. This enzyme defect could also be demonstrated in the white cells of this patient.

Adult↗
PubMed1984

Mitochondrial myopathy with loosely coupled oxidative phosphorylation in a case of Zellweger syndrome. A cytochemical-ultrastructural study.

A newborn female, the second child of consanguineous parents, exhibited general muscle hypotonia, apathy, hepatomegaly and failure to thrive from birth and signs of craniofacial dysmorphia were present. Pipecolic and trihydroxicoprostanoic acid were excreted in the urine and serum transferrin, ferritin and iron were markedly elevated. At the age of 7 weeks the baby died of respiratory insufficiency. Besides malformations of the brain, renal cysts, liver damage with hypoplastic intrahepatic bile ducts and cholestasis, increased storage of iron and cytochemically proven deficiency of peroxisomes in liver and kidney, morphological studied provided evidence of a mitochondrial myopathy in striated muscle with the accumulation of enlarged bizarre mitochondria, showing only minor structural abnormalities. No defects of NADH-reductase, succinate-dehydrogenase or cytochrome-c-oxidase were demonstrated histochemically. Cytochemical-ultrastructural investigation of mitochondrial ATPase revealed activation of the ATP-synthesising enzyme even before the addition of an uncoupler, this indicating loosely coupled oxidative phosphorylation. In addition a high rate of subcellular autophagy with segregation of mitochondria and focal loss of fibrils was present. Muscle damage in Zellweger syndrome appears to be the consequence of complex, interacting metabolic processes. The mitochondrial myopathy thereby induced allows a better understanding of general muscle hypotonia, one of the leading symptoms of this disorder.

Adenosine Triphosphatases↗
PubMed1984

[Morphology of metabolic myopathies].

While muscular lesions in endocrine or metabolic diseases are fairly common primary metabolic myopathies are rare. In these, the metabolic fault is in the muscle fibre itself, which takes on a vacuolated appearance. In the majority of these myopathies there is an abnormality of the glycogen or fat metabolism due to the absence of a specific enzyme in most cases. By contrast, the pathogenesis of the so called mitochondrial myopathies is not yet well understood.

Carnitine↗
PubMed1984

Antiarrhythmic effects of stirocainide in acute myocardial infarction.

Ventricular arrhythmias, especially ventricular fibrillation, are assumed to be a main cause of sudden death during the first 24 h of acute myocardial infarction. Effective prophylaxis and acute suppression of these life-threatening rhythm disturbances are a major therapeutic problem. The present study was undertaken to investigate the efficacy of the new antiarrhythmic compound stirocainide (2-(1-benzylidene)cycloheptenimino-oxyethyl-diisopropylamine -2-butenedionate, Th 494) in suppressing "2nd phase arrhythmias" arising from large anteroseptal myocardial infarctions using a standardized experimental canine preparation. Our results demonstrate that "2nd phase arrhythmias"--i.e. frequent ventricular ectopics, tachycardias, salvos, and R-on-T phenomena--are reduced by 80-90% (sometimes even completely abolished) by stirocainide (dose: 4 mg/kg within 3 min, followed by 300 micrograms/kg X min over a 20-min period). The administration of the drug at the dose used does not produce severe cardiodepression, but intraventricular conduction time is significantly prolonged. Thus, Th 494 is a highly effective antiarrhythmic agent in acute myocardial infarction, and further experimental and clinical investigations on its antiarrhythmic and antifibrillatory properties may lead to beneficial therapeutic results.

Animals↗