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J Schlegel

Publications and source records attributed to J Schlegel.

At least 19 recordsLinked to original sources
PubMed1992

Prooxidant-induced Ca2+ release from liver mitochondria. Specific versus nonspecific pathways.

Ca2+ release from mitochondria can be induced by a variety of chemically different prooxidants. Release induced by these compounds is possibly regulated by protein mono(ADP)ribosylation, and leaves mitochondria initially intact. Excessive "cycling" (continuous release and uptake) of Ca2+ by mitochondria leads to their damage, as shown by a decreased membrane potential, fast Ca2+ release, and impairment of ATP synthesis. When cycling is prevented by Ca2+ chelators or by inhibition of the uptake route with ruthenium red, prooxidants still induce Ca2+ release but mitochondria remain intact. It has recently been suggested that formation of a "pore" in the inner mitochondrial membrane participates in the Ca2+ release mechanism. We find that the prooxidant-induced Ca2+ release is not paralleled by sucrose entry into, or K+ release from, or swelling of mitochondria, provided Ca2+ cycling is prevented. Thus, the prooxidant-induced Ca2+ release does not require formation of a "pore." We conclude that the release occurs via a specific pathway.

Animals↗
PubMed1992

'Pore' formation is not required for the hydroperoxide-induced Ca2+ release from rat liver mitochondria.

It has recently been suggested by several investigators that the hydroperoxide- and phosphate-induced Ca2+ release from mitochondria occurs through a non-specific 'pore' formed in the mitochondrial inner membrane. The aim of the present study was to investigate whether 'pore' formation actually is required for Ca2+ release. We find that the t-butyl hydroperoxide (tbh)-induced release is not accompanied by stimulation of sucrose entry into, K+ release from, and swelling of mitochondria provided re-uptake of the released Ca2+ ('Ca2+ cycling') is prevented. We conclude that (i) the tbh-induced Ca2+ release from rat liver mitochondria does not require 'pore' formation in the mitochondrial inner membrane, (ii) this release occurs via a specific pathway from intact mitochondria, and (iii) a non-specific permeability transition ('pore' formation) is likely to be secondary to Ca2+ cycling by mitochondria.

Animals↗
PubMed1992

[Primary pulmonary nodular amyloidosis and multiple emphysematous bullae in Sjögren syndrome].

The authors report on a very rare case of an isolated primary nodular pulmonary amyloidosis with multiple emphysematous bullae in Sjögren's syndrome. The circular foci present in both lungs in disseminated form were immunohistochemically speaking amyloid deposits of the AL-lambda type. There were no pointers to other organ manifestations or monoclonal immunoglobulins in the serum and/or urine.

Amyloid↗
PubMed1991

Inhibition by cyclosporine A of the prooxidant-induced but not of the sodium-induced calcium release from rat kidney mitochondria.

The use of the immunosuppressive drug cyclosporine A (CSA) is restricted by its nephrotoxicity. Perturbation of Ca2+ homeostasis has been implicated in chemical toxicity. Mitochondria, a key regulator of Ca2+ homeostasis, may be a target of the drug. Here we show that CSA inhibits at low concentrations the prooxidant-induced but not the sodium-induced Ca2+ release from rat kidney mitochondria. CSA does not affect Ca2+ uptake by mitochondria. Inhibition of Ca2+ release is due to inhibition of intramitochondrial enzymatic hydrolysis of NAD+ to ADP-ribose and nicotinamide. These findings suggest a very specific effect of CSA on mitochondrial Ca2+ release by which the drug interferes with cellular Ca2+ homeostasis. This is possibly the basis of CSA nephrotoxicity.

Adenosine Diphosphate Ribose↗
PubMed1991

Chromosome numbers and DNA-content in intracerebrally transplanted experimental gliomas.

Serially transplanted experimental tumors of the central and peripheral nervous system can be used as models to investigate open questions in human neurooncology. Altered susceptibility of higher passages to chemotherapy might be correlated with chromosome number and DNA-content variations which would be partly expressed as changes in proliferation behaviour. Karyotypes therefore were analysed in the 73rd to 90th generations of transplanted experimental gliomas. Wide variation of chromosome number was observed; 2 major types of distribution occurred, the one presenting with, the other without stemlines. Large chromosomes # 1 and # 4 were often monosomic, while small chromosomes of ## 8 to 20 were increased up to the fivefold. Lines with prominent and few markers were observed. On the whole, cells of the proliferating pool of the tumor had to be considered as hypotetraploid. Comparison of chromosome numbers and DNA content gave good correlation; differences between the 2 were explained by the fact that only the number of chromosomes was taken into account, regardless of whether small or large chromosomes were lacking or in excess. When intracerebrally transplanted tumors had been previously treated by administration of BCNU, the DNA content was altered, indicating an increased share of diploid cells in the proliferation pool. Results are at variance with earlier findings in tissue cultures of directly induced malignant gliomas and neurinomas in rats. The findings in transplanted tumors can be interpreted as a result of increased malignancy in transplantation tumors, documented by rapid growth in the animal and dedifferentiated histologic morphology.

Animals↗
PubMed1991

[Data on methods in methacholine inhalation provocation tests (dose-response relationship)].

The cholinergic agonist Methacholine is widely used in unspecific inhalation provocation tests. The maximum changes in lung function take place within two minutes after inhalation. The following spontaneous regression of bronchoconstriction to baseline is prolonged. Therefore, cumulative dose response curves are possible to do. The results of those tests are very dependent on the methods used. Strict standardization of the individual method is necessary. One possible inhalation provocation technique is described.

Asthma↗
PubMed1990

Mitochondrial creatine kinase from chicken brain. Purification, biophysical characterization, and generation of heterodimeric and heterooctameric molecules with subunits of other creatine kinase isoenzymes.

In a recent study it has been shown that mitochondrial creatine kinase from chicken brain (Mia-CK) and heart (Mib-CK) are two distinct isoenzymes differing in ten out of the thirty N-terminal amino acids (Hossle, J.P., Schlegel, J., Wegmann, G., Wyss, M., Böhlen, P., Eppenberger, H.M., Wallimann, T., and Perriard J.C. (1988) Biochem. Biophys. Res. Commun. 151, 408-416). The present article describes the purification and biophysical characterization of the mitochondrial creatine kinase isoenzyme from chicken brain (Mia-CK). Gel permeation chromatography, direct mass measurements of individual molecules by scanning transmission electron microscopy, and analytical ultracentrifugation confirmed the existence of two different oligomeric forms, dimeric and octameric Mia-CK, with molecular masses of 85 kDa and 306-352 kDa and with sedimentation constants of 4.9-5.3 and 11.6-12.0 S, respectively. In addition, it was tested if Mia- and Mib-CK can form heterodimeric and heterooctameric molecules with subunits of other CK isoenzymes. By denaturation in urea or guanidine hydrochloride and subsequent renaturation, MiaMib-CK and surprisingly also MiaM-CK heterodimers could be generated. In contrast, no heterodimers were obtained between Mib- and M- or B-CK. Furthermore, reoctamerization of a mixture of Mia- and Mib-CK homodimers led to the formation of MiaMib-CK heterooctamers. In these heterooctamers, the Mia- and Mib-CK homodimers remained the fundamental building blocks. No subunit exchange between adjacent dimers within the heterooctamer could be observed even after storage for 3 months at 4 degrees C. The relevance of these data on the structural organization of the Mi-CK octamer and on the physiological aspects of tissue-specific isoenzyme expression are discussed.

Amino Acid Sequence↗
PubMed1990

Cyclosporine A inhibits mitochondrial pyridine nucleotide hydrolysis and calcium release.

Mitochondria participate in the maintenance of cellular Ca2+ homeostasis. Here we show that the immunosuppressive drug cyclosporine A at low concentrations inhibits release but not uptake of Ca2+ by mitochondria. Prevention of Ca2+ release is due to inhibition of intramitochondrial enzymatic hydrolysis of NAD to ADP-ribose and nicotinamide. These findings suggest a mechanism by which cyclosporine A interferes with cellular Ca2+ homeostasis, and may be related to the immunosuppressive and cytotoxic properties of the drug.

Alloxan↗
PubMed1990

[Persisting alveolitis after Legionella pneumonia].

Pneumonia was diagnosed radiologically in three patients (43, 54 and 58 years old, respectively), presenting with temperatures between 39 degrees and 40 degrees C, cough and weight loss. These signs persisted for 6, 7 and 13 weeks, respectively, but the pathogens could not be cultivated. Lung function analysis showed partial respiratory insufficiency with extensive restrictive impairment of ventilation. Samples of lung tissue were obtained in all three cases and histology revealed fibrosing alveolitis. In two patients serology yielded antibody titres of 1:512 and in one patient of 1:128, against Legionella pneumophila. Treatment with 1 g erythromycin three times daily was unsuccessful. Therefore, the patients were given prednisone at an initial dosage of 50-100 mg which was subsequently reduced. Lung function normalised during this treatment course, radiological findings and antibody titres receded. Hence, treatment with corticosteroids should be attempted if there is an urgent suspicion of fibrosing alveolitis caused by Legionella pneumophila, after having excluded a florid infectious pneumonia and after failure of erythromycin treatment.

Adult↗
PubMed1990

Functional studies with the octameric and dimeric form of mitochondrial creatine kinase. Differential pH-dependent association of the two oligomeric forms with the inner mitochondrial membrane.

Phosphate extraction of mitochondrial creatine kinase (Mi-CK, EC 2.7.3.2) from freshly isolated intact mitochondria of chicken cardiac muscle, after short swelling in hypotonic medium, yielded more than 90% of octameric and only small amounts of dimeric Mi-CK as judged by fast protein liquid chromatography-gel permeation analysis of the supernatants immediately after extraction of the enzyme. In extraction buffer, octameric Mi-CK displayed a tendency to dissociate, albeit at a slow rate with a half-life of approximately 3-5 days, into stable dimers. Experiments with purified Mi-CK octamers or dimers, or defined mixtures thereof, incubated under identical conditions with Mi-CK-depleted mitoplasts revealed that both oligomeric forms of Mi-CK can rebind to mitoplasts. However, the association of Mi-CK was strongly pH-dependent and, in addition, octameric and dimeric Mi-CK showed different pH dependences of rebinding. Therefore, it was possible under certain pH conditions to rebind either both oligomeric forms or selectively the octamers only. Furthermore, evidence is presented that Mi-CK dimers partially form octamers upon rebinding to the inner membrane. The differential association of the two oligomeric Mi-CK forms with the inner mitochondrial membrane together with the dynamic equilibrium between octameric and dimeric Mi-CK (Schlegel, J., Zurbriggen, B., Wegmann, G., Wyss, M., Eppenberger, H.M., and Wallimann, T. (1988) J. Biol. Chem., 263, 16942-16953) suggest that both oligomeric forms are physiologically relevant. A change in the octamer to dimer ratio may influence the association behavior of Mi-CK in general and thus modulate mitochondrial energy flux as discussed in the phosphoryl creatine circuit model (Wallimann, T., Schnyder, T., Schlegel, J., Wyss, M., Wegmann, G., Rossi, A.-M., Hemmer, W., Eppenberger, H.M., and Quest, A.F.G. (1989) Prog. Clin. Biol. Res. 315, 159-176.

Animals↗
PubMed1990

[Spirometry].

Explore the source record for details and available documents.

Airway Resistance↗
PubMed1990

[Fading of the provocation effect following inhaled provocation with carbachol].

The results of the present study aimed at establishing the subsidence of the effect of inhalative provocation with carbachol show that no ceiling activity is reached. Rather, following a maximum effect that is achieved after approximately 2 minutes, spontaneous subsidence of the provocation-related changes occurs. The average duration of this subsidence to below the level of change that is considered significant for the respective measured parameter was between 20 and 25 minutes.

Adult↗
PubMed1989

Further characterization of contact sites from mitochondria of different tissues: topology of peripheral kinases.

A membrane fraction of intermediate density between inner and outer membrane was isolated by density gradient centrifugation from osmotically disrupted mitochondria of rat liver, brain, and kidney. The fraction was hexokinase rich and could therefore be further purified using specific antibodies against hexokinase and immunogold labelling techniques. In agreement with recent findings the gradient fraction which cosedimented with hexokinase contained the boundary membrane contact sites because it was composed of outer and inner membrane components and beside hexokinase, was enriched also by activity of creatine kinase and nucleoside diphosphate kinase. In contrast the activity of adenylate kinase appeared to be concentrated beyond the contact sites in the outer membrane fraction. By employing surface proteolysis analysis and specific blockers of the outer membrane pore we observed that the location of the kinases relative to the membrane components in the contact fraction resembled that of intact mitochondria. This specific organization of some peripheral kinases in the contact sites suggested an important role of the voltage dependence of the outer membrane pore, in that the pore may become limiting in anion exchange because of influence of the inner membrane potential on the closely attached outer membrane. Such control of anion exchange would lead to a dynamic compartmentation at the mitochondrial surface by the formation of contact sites, which may explain the preferential utilization of cytosolic creatine by the mitochondrial creatine kinase, as postulated in the phosphocreatine shuttle.

Adenylate Kinase↗
PubMed1989

Clonidine treatment of Alzheimer's disease.

A loss of cortical noradrenergic innervation may contribute to the intellectual deterioration in Alzheimer's disease. To test the hypothesis that noradrenergic replacement may confer symptomatic benefit, a double-blind, placebo-controlled therapeutic trial with clonidine hydrochloride (Catapres), a centrally active noradrenergic receptor agonist, was undertaken in eight patients with the clinical diagnosis of Alzheimer's disease. No statistically significant changes in cognitive function were found over a range of doses, including those that produced clinically observable side effects. These preliminary results indicate a need for alternative noradrenergic replacement strategies in Alzheimer's disease.

Aged↗
PubMed1989

Dopamine and memory function in Parkinson's disease.

Response fluctuations in motor function, complicating long-term dopaminomimetic therapy of Parkinson's disease, may extend to the cognitive realm. To evaluate the effect of levodopa treatment both on attention as well as acquisition and retrieval of memory tasks, parkinsonian patients were examined neuropsychologically both while medicated with levodopa/carbidopa ("on") and when the medication's antiparkinsonian effect had worn off ("off"). Significant cognitive differences emerged only on the delayed recall of complex verbal materials, where patients when "on" performed better compared with their "off" state. Comparison of change scores across states (administration or withholding of levodopa/carbidopa between acquisition and retrieval, "off" to "on" or "on" to "off"), revealed no substantial differences as a function of dopaminomimetic therapy. These results support the view that slight changes in cognition are associated with dopaminomimetic therapy of Parkinson's disease, but that these changes may be task-specific.

Aged↗