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Biomedical subjects

B Rösler

Publications and source records attributed to B Rösler.

At least 19 recordsLinked to original sources

Kinetics of hepatitis C (HCV) viraemia and quasispecies during treatment of HCV associated cryoglobulinaemia with pulse cyclophosphamide.

OBJECTIVE: To investigate the effect of pulse cyclophosphamide treatment on hepatitis C virus (HCV) kinetics and quasispecies in interferon alpha (IFNalpha) resistant HCV related cryoglobulinaemic vasculitis. METHODS: Reports on two patients with severe manifestations of HCV related cryoglobulinaemia who failed to respond to interferon alpha are given. Both patients were treated with pulse cyclophosphamide (750-1000 mg/month for six and 11 months, respectively). HCV RNA was quantified and HCV quasispecies determined in cryoprecipitates and supernatants before and during treatment. RESULTS: Cryocrit and complement activation decreased in both patients with rebound of cryocrit in one case during continuing pulse cyclophosphamide treatment. Vasculitic symptoms improved. Alanine aminotransferase (ALT) levels and HCV viral load (0.2-0.4 log) increased slightly and reached pretreatment levels after cyclophosphamide was stopped. A highly heterogeneous quasispecies was found in the cryoprecipitate and supernatant of one patient, whereas the viral population was homogeneous in the other patient. After six cycles of cyclophosphamide, viral distances decreased non-significantly. However, phylogenetic analysis showed the evolution of distinct viral strains in one patient and replacement of the main viral population by another population in the second patient. CONCLUSIONS: Immunosuppressive treatment with pulse cyclophosphamide has a temporary limited effect on HCV associated cryoglobulinaemia and leads to a reversible increase of ALT levels and HCV viral load. Short term immunosuppression does not affect the viral heterogeneity as measured by amino acid and nucleotide distances in the hypervariable region 1 of HCV. A change of quasispecies was observed, but further studies are needed to evaluate if this does affect the outcome of IFNalpha treatment in such patients.

Aged↗

Quasispecies analysis in hepatitis C virus infection by fluorescent single strand conformation polymorphism.

Hepatitis C virus (HCV) results frequently in chronic hepatitis and its sequelae liver cirrhosis and hepatocellular carcinoma. Interferon-alpha is at present the most effective treatment, resulting in a sustained response in about 20-25% of patients. HCV genotype, titer and quasispecies determine the success of treatment. In this study, fluorescent single strand conformation polymorphism (f-SSCP) was evaluated for the analysis of HCV quasispecies. Two sera from a chronically HCV-infected patient, obtained 6 years apart, were examined. The hypervariable region I (HVRI) of the HCV genome was amplified by reverse transcription and PCR. The PCR products were cloned and sequenced or fluorescein-labeled and subjected to f-SSCP. Both methods demonstrated a single HCV species in the early serum and multiple quasispecies in the late serum. Single clones of the heterogeneous virus population were used to optimize conditions for f-SSCP. The most important factors were the gel temperature and virus titer. At the optimal running temperature one base exchange in 218 bases was detectable. Repeat extractions and amplifications gave identical results. Dilution of the serum containing multiple quasispecies resulted in a 'loss' of species. Provided the running temperature is optimal and virus titer is sufficient, f-SSCP is shown to be fast and reliable for HCV quasispecies analysis.

Amino Acid Sequence↗

[The importance of S-100 protein positive Langerhans cells and Leu-M1 positive tumor cells for prognosis of papillary thyroid cancer].

In a period of 10 years (1981-90) papillary thyroid carcinomas were found in 124 cases. In 95 cases we were able to perform immunohistochemical studies for Leu-M1 antigen and S-100 protein. The examination of these cases has revealed that the presence of S-100 positive Langerhans cells yields no additional information for the prognosis of the papillary thyroid carcinoma. But we observed that the existence of Leu-M1 positive tumour cells is connected with a poor postoperative course of disease in comparison to Leu-M1 negative tumours.

Antigens, CD↗

[Electron microscopy studies of cilia of the bronchial tree in children with chronic bronchopulmonary diseases].

The results of an ultrastructural analysis of cilia in 30 children at the age of 11 month to 16 years are presented. Children with marked symptoms of chronic bronchitis were consciously chosen for examination. One group of 15 children was suffering from chronic bronchitis with bronchiectases. No bronchiectasis was found in the second group of 15 children with chronic bronchitis. Specific changes were more evident in the first group, whereas nonspecific changes were of equal frequency in both groups. Only in 3 patients of group I generalized specific defects could be demonstrated. In these cases mucociliary clearance was nearly not present. Ultrastructural changes of cilia in children with chronic nonspecific lung diseases enclose a wide spectrum. Compared to it generalized structural defects are rare and only in 3 cases of our study demonstrable (negative selection of a bronchological centre).

Adolescent↗

[What is established in the immotile cilia syndrome?].

For the first time in 1975 ultrastructural defects of the sperm tail and the cilia of the respiratory tract were recognized as causing male sterility and chronic bronchitis. A spectrum of ultrastructural defects leading to a restricted mucociliary clearance and chronic bronchitis was found by further investigations. Whereas genetically determined primary structural defects appear generally, secondary ciliary changes caused by chronic infections are found sporadically and not bound to a fixed pattern. Congenital and acquired specific ciliary alterations in the tubulin-dynein-system should be distinguished from nonspecific acquired alterations. A summary of the presently known ultrastructural changes is illustrated by findings of the authors.

Bronchi↗

[Relation between lipofuscin content and organelle density in pyramidal cells of laminae III and V of area 10 (Brodmann) of the cerebral frontal lobe of humans of different ages].

The areal portion of the lipofuscin granules and mitochondria contained in ultrathin sections, the length of rough endoplasmic reticulum (RER) and the numerical density of ribosomes were determined in the pyramidal cells of layers III and V of area 10 (Brodmann) of the frontal brains of six newly died persons of different ages. This revealed considerable differences in lipofuscin contents and numerical density of organelles between the pyramidal cells and greater values, on an average, for the pyramidal cells of layer III. The comparison of averages for the single brains did not show the continuity nor the age dependence of changes but rather the individual variability of these processes. The expected decrease of the density of organelles with increasing lipofuscin contents was found more frequently only at extremely high values of lipofuscin contents. It becomes evident that even under the conditions of lipofuscin accumulation the permanently necessary physiological renewal of cell structures involved in metabolism is guaranteed over a longer period of time and that their full performance is almost completely unimpaired during this phase.

Adult↗

[Electron microscopic morphometric examinations on the lipofuscin content of pyramidal cells of laminae III and V in area 10 (Brodmann) of the frontal lobe of humans of various ages].

The lipofuscin contents in pyramidal cells of laminae III and V in area 10 (Brodmann) of the frontal brain from 6 men who recently died at different ages without any neurological or psychiatric symptoms were investigated by electronmicroscopic-morphometric methods. The results of this investigation actually do reveal an increase of the lipofuscin with age, but also demonstrate to what extent this process is subject to individual variability. Great differences in the accumulation of the lipofuscin exist among the cells within the same cytoarchitectonic layer. On the other hand wide correspondence between the mean values of both laminae can be stated.

Adult↗

[Morphometric investigation on the changes of the paramembranous structures of the CA 1 hippocampal synapses of trained rats, with special reference to the morphological plasticity of the synapses].

Albino rats aged 13 weeks experienced a single training for bright-dark discrimination in a Y-chamber. 24 hours later after a successful training the paramembranaceous structures of the synapses contrasted by phosphotungstic acid were morphometrically analysed. As a result of this investigation a signifikant reduction of the height and the width of the dense projections was to be stated compared to untrained rats. Likewise the length and the width of the postsynaptic ribbon were reduced in trained rats. But this alteration proved not to be significant.

Animals↗

[Determination of the width of the synaptic cleft in PWS-contrasted rat brain material].

Based on a simple model of the synaptic cleft, some of those procedures that render possible an appraisal of the cleft width starting from cuttings as seen in micrographs are described in this paper. The results of the investigation prove that contrary to figures published previously by other authors, the width of the synaptic cleft is not constant, but exhibits a frequency distribution with a maximum - to - minimum ratio of about ten. Relative frequency in per cent can be approximately expressed as follows: p = 7.7 + 4.1 n with n = 1, 2, 5 ordinal class numbers of cleft width and the according class mid-points 7.62n nm Typflying of synapses according to physiological points of view has turned out to be out of reach.

Animals↗

[Synapse density determination in brain structures based on phosphotungstic acid contrast].

Using the E-PTA procedure of Aghajanian and Bloom we determined the numerical density of synapses in the stratum lacunosun-modeculare of the CA1-region in the hippocampus of male albino rats. On this occasion the sources of error both the natural and the methodical were investigated. As natural causes of remarkable scattering and failing correspondence in the findings the individual variability of the synaptic density and the inhomogeneous distribution of synapses must be taken into consideration. Concerning the methodical sources of error the differences in tissue shrinkage become apparent. But faults resulting from applying morphometric methods are the most serious. The counting of synaptic profiles is based on defined morphological criteria. The portion of the synaptic profiles recorded in this way in relation to all those present in the section depends beside other things on the section thickness. Accordingly the correction factors are in correlation with section thickness. The application of the Floderus correction presupposes the determination of the minimum length of the counted profiles. As a result of these investigated the possibilities for reducing the error have been demonstrated.

Animals↗