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Biomedical subjects

G Hübner

Publications and source records attributed to G Hübner.

At least 91 records · Page 5Linked to original sources
PubMed1991

Fatal infantile mitochondrial cardiomyopathy and myopathy with heterogeneous tissue expression of combined respiratory chain deficiencies.

A 5-month-old boy died of progressive heart failure that started at the age of 3 months. Autopsy revealed a mitochondrial cardiomyopathy and a mitochondrial myopathy of the limb muscle and diaphragm. Cytochemically random defects of cytochrome c oxidase were visualized by light and electron microscopy in the diaphragm and especially the heart muscle, the limb muscle showing a diffuse attenuation whereas the liver and kidneys reacted normally. The activities of NADH-dehydrogenase (complex I) and cytochrome c oxidase (complex IV) were severely diminished (20% residual activity of controls) in the skeletal and heart muscle. In the heart, succinate cytochrome c reductase (complex II/III) was additionally decreased to the same degree. Loss of cytochrome c oxidase activity was based on a reduction of both mitochondrial and nuclear derived subunits in the heart and diaphragm as revealed by immunohistochemical analysis, whereas the limb muscle showed a normal immunoreactive protein content. The results illustrate heterogeneous tissue expression of respiratory chain enzyme defects and demonstrate that a cardiomyopathy may be the leading presentation of a mitochondrial disorder in early infancy.

Cardiomyopathies↗
PubMed1991

Yeast phosphofructokinase: studies on thiol reactivity of a cross-linked enzyme form.

Cross-linked yeast phosphofructokinase exhibiting the basic regulatory properties of the unmodified enzyme but no cooperativity with respect to the substrate fructose 6-phosphate was subjected to stopped-flow thiol titration in order to study the influence of allosteric effectors on the level of protein conformation. As found for native phosphofructokinase, the cross-linked enzyme revealed at least two classes of cysteinyl residues which can be distinguished by their reactivity towards 5,5'-dithiobis-(2-nitrobenzoic acid). In spite of the restricted conformational flexibility caused by the intramolecular cross-linking, several fructose phosphates and AMP were capable of diminishing the apparent first-order rate constant (k) of modification of the fast reacting thiol groups by Ellman's reagent. In the presence of ATP, a drastic decrease of the k-value by more than one order of magnitude became apparent. The data are appropriate to support the hypothesis of the existence of multiple conformational determinants in octameric yeast phosphofructokinase and contribute to the understanding of the extremely different stability of the enzyme in the presence of either fructose 6-phosphate or ATP with respect to proteolytic degradation.

Adenosine Triphosphate↗
PubMed1990

An X-ray solution scattering study of the cofactor and activator induced structural changes in yeast pyruvate decarboxylase (PDC).

Structure and activation pattern of pyruvate decarboxylase (PDC) from yeast was studied by synchrotron radiation X-ray solution scattering. The results give a direct proof that the reversible deactivation of PDC at pH 8.0 is accompanied by the dissociation of the tetrameric holoenzyme into dimeric halves. The kinetics of this process was followed. At pH 6.5 the dimeric halves reassociate to a tetramer even in the absence of cofactors. The changes of the scattering pattern upon binding of the substrate-like activator pyruvamide indicate that the structure expands in the course of the enzyme activation.

Apoenzymes↗
PubMed1990

[Fasciitis in granulomatous myositis--an atypical manifestation of sarcoidosis?].

We report about two female patients with a histopathological proven granulomatous myositis associated with a fasciitis. One patient showed noncaseating granulomas in the muscle fascia. She suffered from symmetrical contractures of the digital flexors and ankles. The second patient showed uveitis and polyneuropathy, too. In addition, increased activities of the angiotensin-converting-enzyme and lysozyme in the sera suggested that both cases represent a new form of sarcoidosis.

Adipose Tissue↗
PubMed1990

Aneurysms and vacuolar degeneration of cerebral arteries in late-onset acid maltase deficiency.

We present a case of late-onset acid maltase deficiency (AMD) with pronounced involvement of the liver and skeletal muscles. In addition, and in contrast to other adult cases of AMD, the case presented here shows CNS pathology with hypodense and hyperintense white matter areas on CT and MRI scans, and myelin changes ranging from focal areas of demyelination to necrosis. Neuropathologic changes seem to be related to unusual vascular pathology consisting of vacuolar degeneration of small and large arterial blood vessels. Vacuoles of varying size, partly filled with granular PAS-positive material, were found in pericytes and smooth muscle cells of arterial vessel walls. Electron microscopy revealed lysosomal and cytoplasmic free glycogen in smooth muscle cells in the intima of large cerebral arteries as well as in pericytes of arterioles and capillaries. Accumulation of glycogen locally was associated with severe cellular damage and necrosis. The formation of a great number of small aneurysms of intracerebral arteries is thought to be the result of cell damage in the vessel walls.

Adult↗
PubMed1990

Yeast phosphofructokinase: pre-steady-state and stationary kinetic studies on a cross-linked enzyme form.

A cross-linked form of yeast phosphofructokinase in which up to four of the subunits of the octameric molecule were found covalently linked by dimethyl suberimidate exhibits no cooperativity with respect to fructose 6-phosphate and is only weakly inhibited by ATP. The modified enzyme is activated by AMP and fructose 2,6-bisphosphate. Both effectors abolish ATP inhibition even at low concentration of fructose 6-phosphate and increase the affinity of modified phosphofructokinase to fructose 6-phosphate but are without significant effect on the respective maximum activity. The corresponding kinetic patterns exhibit similarity to those of the native enzyme at high concentration of fructose 6-phosphate. In comparison to native phosphofructo-kinase the extent of activation by AMP and fructose 2,6-bisphosphate is of minor amount. As shown for native phosphofructokinase, the enzyme which had been cross-linked in the absence of any effector shows a lag phase of product formation. This initial transient phase completely disappears if the enzyme is modified in the presence of fructose 6-phosphate, fructose 1,6-bisphosphate, and fructose 2,6-bisphosphate, respectively. The same result is obtained by preincubation of the enzyme cross-linked in the absence of any effector with each of these fructose phosphates. The kinetic properties of the modified enzyme indicate that cooperativity with respect to fructose 6-phosphate is not a prerequisite for the allosteric modulation of enzyme activity by AMP and fructose 2,6-bisphosphate and support the idea of multiple conformational determinants in yeast phosphofructokinase. The results suggest that moderate intramolecular cross-linking can provide a simple experimental tool to stabilize different conformational states of an enzyme.

Adenosine Monophosphate↗
PubMed1990

Phosphofructokinase from baker's yeast: studies on the initial kinetics and the fast reacting thiol groups of a proteolytically modified active enzyme form.

The initial kinetics as well as the reactivity of the fast reacting thiol groups of a tetrameric form of phosphofructokinase from baker's yeast (called 12 S-enzyme), obtained by limited proteolysis in the presence of ATP were studied by the stopped-flow technique. Before attaining the steady state, the reaction shows a lag phase in the product formation, the duration of which decreases with increasing enzyme concentration. The lag phase disappears after preincubation of the enzyme with either fructose 6-phosphate, fructose 1,6-bisphosphate or fructose 2,6-bisphosphate. The occurrence of an initial transient phase suggests that the enzyme converts from a state of low activity into a highly active one after starting the reaction. The modified enzyme was found to contain two fast reacting cysteinyl residues with respect to their reactivity towards 5,5'-dithiobis(2-nitrobenzoic acid). Fructose 6-phosphate, fructose 1,6-bisphosphate and fructose 2,6-bisphosphate, respectively, decrease the reactivity of this class of thiol groups but not the total number of titrable cysteins. This result supports the hypothesis of a conformational change as a consequence of the effector binding.

Kinetics↗
PubMed1990

Cross-linking of pyruvate decarboxylase. Characterization of the native and substrate-activated enzyme states.

In order to demonstrate the role of the protein component of pyruvate decarboxylase in the mechanism of substrate activation, we have isolated and characterized two states of the enzyme, the non-activated and the substrate-activated state, by covalent linking with bifunctional reagents. Because of the fact that modification of the reactive amino groups by 2,4,6-trinitobenzenesulfonic acid or methyl propionimidate influences neither the catalytic nor the regulatory properties of pyruvate decarboxylase, we used bisimidates of different chain length in the modification experiments. Both the non-activated and the substrate-activated enzyme states could be characterized separately. The lag phase of product formation as a typical property of the native enzyme disappeared completely when the enzyme had been cross-linked in the presence of the substrate. The permanently activated enzyme state shows 85% of the activity of native pyruvate decarboxylase and is exclusively stabilized by intra-subunit links. Elimination and subsequent reincorporation of the cofactors thiamine pyrophosphate and magnesium ions resulted in a complete regaining of the properties of the permanently activated enzyme form. An inactive enzyme form was obtained after cross-linking of non-activated pyruvate decarboxylase at low ionic strength (less than 0.01). Using a disulfide-containing linker we could prove that the inactivity of the obtained enzyme preparation was only the result of the incorporated cross-links and not that of denaturation.

Cross-Linking Reagents↗
PubMed1990

[Hermansky-Pudlak syndrome in 2 brothers with lung fibrosis].

This is a report on two brothers with the Hermansky-Pudlak syndrome who developed pulmonary fibrosis. In the first, a gradual course lasting 13 years was observed, the patient finally died of long-standing colitis. His brother died of progressive respiratory failure 15 months after the subjective onset of the disease. Immunosuppressive therapy proved ineffective.

Adult↗
PubMed1989

[Progressive multifocal leukoencephalopathy in Wegener's granulomatosis in relation to therapy with cyclosporin A].

A female patient with Wegener's granulomatosis developed severe bone marrow depression after two years treatment with cyclophosphamide. Corticosteroids alone could not sufficiently suppress disease activity, therefore additive therapy with Cyclosporin A was started. Four weeks later the patient developed a central nervous system disorder with affective disturbances and progressive somnolence. However, inspite of intensive diagnostic procedures, no definite diagnosis could be established. After another two months she died. Post-mortem-examination showed progressive multifocal leukoencephalopathy. An association between immunosuppressive therapy and reactivation of JC-Virus is suggested.

Brain↗
PubMed1989

Spontaneous immune complex orchitis in brown Norway rats.

Immune complexes occur spontaneously in the testis of Brown-Norway (BN) inbred rats between the basal lamina of the seminiferous tubules and the outer lamina of the myoid testicular cells. The deposits can be detected immunohistologically (IgG; C3) and by electron microscopy. The immune complexes appear between the 8th and 12th weeks of life, increase in amount up to the 30th week and decrease thereafter. After about the 20th week, of life, 15% of the animals show destruction of the germinal epithelium accompanied by an infiltration of lymphocytes and plasma cells. The final stage of this disease, which initially shows no signs of inflammation, is characterized by diffuse tubular atrophy. However, up to the 70th week of life, 85% of the animals with immune complexes show no pathological alterations. Antibodies eluated from the testes react with spermatocytes I and structures close to the lumen of the seminiferous tubules, but not with mature sperms. Serum antibodies to sperms occur in about 25% of the BN rats, but the presence of these antibodies shows no correlation with the immunohistological findings. This newly described spontaneous immune complex orchitis is regarded as a further example of an in-situ-induced immune complex disease. The observations made here can be compared with those in (peri-) membraneous glomerulonephritis, another example of a disorder resulting from in-situ-formation of immune deposits.

Animals↗
PubMed1989

Myositis caused by Borrelia burgdorferi: report of four cases.

Myositis was proven histopathologically in 4 patients (age range 36-66 years) who suffered from early or late stages of Borrelia burgdorferi infection. Muscle weakness was present in 3 patients, 1 complaining of additional myalgias. One man came to medical attention because of skin discoloration and swelling of one leg. Deep biopsy from skin, fascia and muscle revealed acrodermatitis chronica atrophicans, panniculitis, fasciitis, and myositis, respectively. Creatine kinase was slightly elevated in 3 cases and normal in one. Infiltrates were found in the perimysium and within the muscle bundles, mainly around small vessels. The infiltrates consisted of many B cells and T4 lymphocytes with fewer cytotoxic T cells, suggesting that Borrelia myositis might be due to a local immune response to unknown Borrelia antigens. Cultivation of Borrelia from muscle was not successful. Antibiotic therapy cured the myositis.

Adult↗
PubMed1989

Fatal mitochondrial myopathy with cytochrome-c-oxidase deficiency and subunit-restricted reduction of enzyme protein in two siblings: an autopsy-immunocytochemical study.

Lack of cytochrome-c oxidase activity and of cytochromes aa3 + b has been reported previously in the skeletal muscle of one of two siblings (Müller-Höcker et al, 1983). The present study reports a deficiency of immunoreactive enzyme protein in the skeletal muscle of both siblings, who had an identical fatal clinical course. In all specimens the defect did not involve the whole enzyme protein, but was selectively expressed in the mitochondrially derived subunits II/III and nuclear coded subunits VIIbc. Neither the specific fibers of the muscle spindles nor the mitochondria of the heart, liver, kidneys, vessel walls and/or gastrointestinal tract were affected. These results are most consistent with a primary nuclear defect being responsible for the organ specific and subunit selective expression of the enzyme defect.

Antibodies↗
PubMed1989

Rapid diagnosis of intestinal Bacteroides species by means of the immunofluorescence.

Rapid methods serving the detection of intestinal Bacteroides species in clinical specimens are of great significance. For this purpose, an identification of the species is possible at present only by means of immunofluorescence (IF). Using preparations of antigens of different intestinal Bacteroides species (B. fragilis, B. thetaiotaomicron, B. uniformis, B. ovatus, and B. distasonis) as well as immune sera prepared against them, the presented results have shown the possibility of specific identification of the species involved by means of direct and indirect IF, respectively. However, it could be demonstrated that the direct IF results in a more brilliant appearance of the bacteria than the indirect procedure. Convincing results could be obtained also in the investigation of clinical specimens by means of the direct IF using a pool of conjugated immunoglobulin fractions (sensitivity 88%, specificity 100%). Therefore, the direct method to detect intestinal Bacteroides species by IF should be preferred.

Animals↗
PubMed1989

Influence of trivalent chromium on the beta-cell function.

Application of trivalent chromium (daily 1 mg, p.o.) to pregnant rats in the time of gestation and thereafter--beginning with the first day of the gestation and lasting for 50 days--did not change the i.p. glucose tolerance of the adult animals. The insulin concentration in serum 30 min after glucose loading was decreased significantly. The basal concentration of serum insulin of neonates was diminished, too. The insulin content of the whole pancreas was decreased in mother animals and increased in neonates. Secretion of insulin by isolated islets of the neonatal animals was unchanged. Insulin biosynthesis of the islets of these animals was increased in presence of 6 and 15 mM glucose, respectively. These data suggest an effect of trivalent chromium on endocrine pancreas.

Animals↗