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Biomedical subjects

J Winter

Publications and source records attributed to J Winter.

At least 163 records · Page 9Linked to original sources
PubMed1991

Nucleocapsid or spike protein-specific CD4+ T lymphocytes protect against coronavirus-induced encephalomyelitis in the absence of CD8+ T cells.

To investigate the antiviral CD4+ T cell response in coronavirus MHV-JHM-induced encephalomyelitis, spleen and thymic lymphocytes from diseased rats were stimulated in culture with virus Ag, expanded and tested for their specificity to viral proteins and nucleocapsid (N) and spike (S) proteins that had been expressed in bacteria. A strong T cell response specific for N was measurable during acute disease, whereas S-specific T cells were only detectable in rats with a later onset of disease. CD4+ T cell lines with specificity for virus and either N or S protein were established and their influence on the course of a mouse hepatitis virus-JHM infection was investigated. All lines were of the CD4+ phenotype. Both N and S protein-specific CD4+ T cells conferred protection to infected Lewis rats and reduced the amount of infectious virus in the central nervous system. After transfer of CD4+ T cells and challenge with virus, an increase in the antiviral IgM response occurred, but neutralizing antibodies were not detectable during the period of virus clearance. Previous CD8+ cell depletion did not abrogate protection mediated by CD4+ T cell line transfer.

Animals↗
PubMed1991

Purification and properties of F420- and NADP(+)-dependent alcohol dehydrogenases of Methanogenium liminatans and Methanobacterium palustre, specific for secondary alcohols.

The F420-dependent alcohol dehydrogenase (ADH) of Methanogenium liminatans and the NADP(+)-dependent ADH of Methanobacterium palustre were purified to homogeneity. The native F420-dependent ADH of Mg. liminatans had a molecular mass of 150 kDa and consisted of four (presumably identical) subunits with a mass of 39 kDa. The temperature optimum was 42 degrees C, the optimum pH 6.0 and NaCl or KCl were inhibitory. The NADP(+)-dependent ADH of Mb. palustre had a molecular mass of 175 kDa and consisted also of four (presumably identical) subunits with a mass of 44 kDa. The temperature optimum was 60 degrees C, the optimum pH 8.0 and optimal activity was observed in the presence of 500 mM NaCl or KCl. The ADHs of both organisms catalysed the oxidation of various secondary and cyclic alcohols to the corresponding ketones and the reverse reaction. No primary alcohols were apparently oxidized. The NADP(+)-dependent ADH of Mb. palustre contained 4-8 mol atoms zinc/mol enzyme and was inhibited by low concentrations of iodoacetate and 4-hydroxymercuribenzoate, whereas the F420-dependent ADH of Mg. liminatans presumably contained no zinc ions and was inhibited by 1,10-phenanthroline or high concentrations (e.g. 100 microM) of 4-hydroxymercuribenzoate. Polyclonal antibodies against the NADP(+)-dependent ADH of Mb. palustre precipitated only the homologous ADH. A precipitation of the NADP(+)-dependent ADH of Methanocorpusculum parvum required a 10-fold higher antibody concentration, showing at least a distant relationship of both ADHs. Antibodies against the NADP(+)-dependent ADH of Mcp. parvum, however, formed precipitates with the homologous ADH of Mcp. parvum and with the NADP(+)-dependent ADH of Mb. palustre. They also formed precipitates with the ADH of Thermoanaerobium brockii, which is not related to methane bacteria. Antibodies against the F420-dependent ADH of Mg. liminatans reacted only with the homologous enzyme and did not form precipitates with NADP(+)-dependent ADHs. No immunological relation of the NADP(+)- or F420-dependent ADHs of methanogens with ADH of yeast or horse liver was found. In accordance with the immunological data, the N-terminal amino acid sequences of the NADP(+)-dependent ADHs of Mb. palustre and Mcp. parvum had a high degree of similarity, whereas the N-terminal amino acid sequence of the ADH of Mg. liminatans revealed no similarity with the two NADP(+)-dependent enzymes.

Alcohol Oxidoreductases↗
PubMed1991

[Cost-effectiveness of lowering of blood cholesterol using simvastatin and cholestyramine].

With use of a model of the costs and effects of cholesterol lowering therapy in the primary prevention of coronary heart disease, the cost-effectiveness of simvastatin and cholestyramine in the Netherlands have been estimated. Costs per year of life saved by cholestyramine therapy are several times greater than those of simvastatin therapy and compared unfavorably with those of generally accepted health care programs in the Netherlands. Cholesterol-lowering with simvastatin in men can be cost-effective when therapy is initiated at an early age. At cholesterol levels between 6.5 and 8 mmol/l, however, therapy should be restricted to men with at least one, preferably two additional risk factors such as hypertension or diabetes mellitus. Among women, cholesterol lowering can only be cost-effective when therapy is limited to women with diabetes mellitus or severely elevated serum cholesterol levels.

Adult↗
PubMed1991

Reproducibility of the measurement of ciprofloxacin concentration in bronchial mucosa.

The reproducibility of ciprofloxacin estimations was investigated in duplicate samples of bronchial mucosa from patients undergoing fibreoptic bronchoscopy. At the time of biopsy, venous blood was collected from each patient. Between 3.5 and 5.0 h after dosing, penetration (%) into the mucosa was 162.13 (S.D. 19.77). The correlation coefficient (Pearson's) between duplicate samples was 0.93. The confidence limits (95%) for a single measurement were +/- 1.47 mg/kg.

Bronchi↗
PubMed1991

Bronchial penetration of ofloxacin after single and multiple oral dosage.

Simultaneous bronchial biopsy and serum samples were obtained from 14 patients after a single oral dose of 200 mg ofloxacin and from ten patients during the course of multiple dose oral treatment, (200 mg ofloxacin bd) for acute exacerbations of chronic bronchitis. Duplicate bronchial samples from different parts of the lung were obtained from five patients. Concentrations in bronchial mucosa were equal to or higher than serum concentrations. There were no statistically significant differences in concentrations after single or multiple doses but there appeared to be a trend towards higher concentrations after multiple doses. After a single dose bronchial and serum concentrations ranged from 1.3 to 15.5 mg/kg and from 0.1 to 5.0 mg/l, respectively, between 1 and 6 h after dosing. After multiple dosing of patients with acute exacerbations of chronic bronchitis bronchial and serum concentrations ranged from 1.7 to 21.0 mg/kg and 1.0 to 6.1 mg/l, respectively between 1 and 12 h. The percentage difference in ofloxacin concentrations in five duplicate bronchial samples from different parts of the lung was -4%, (95% confidence intervals +22% to -30%). Thus, the model of bronchial sampling after single dosing of patients before diagnostic bronchoscopy gave results that were similar to those obtained after multiple dosing of patients with acute exacerbations of chronic bronchitis. After multiple dosing ofloxacin concentrations were greater than 1 mg/l or greater than 1 mg/kg in serum and bronchial mucosa throughout the dosing interval, which is above the MIC for most respiratory pathogens.

Administration, Oral↗
PubMed1991

Clostridium orbiscindens sp. nov., a human intestinal bacterium capable of cleaving the flavonoid C-ring.

Clostridium orbiscindens sp. nov. is an obligate anaerobe that is capable of cleaving the C-3-C-4 bond of the natural anticarcinogen quercetin. The metabolic products, 3,4-dihydroxyphenylacetic acid and presumably phlorglucinol, are not known to possess anticarcinogen properties. This organism was isolated from human feces. On sheep blood agar plates C. orbiscindens forms minute, irregular, convex, gray or white, shiny, smooth, nonhemolytic colonies. It is beta-hemolytic on rabbit blood agar. The motile peritrichous rods are gram variable. Subpolar spores are common. Cultures are resistant to 80 degrees C for 10 min. Capsules are absent. This asaccharolytic organism does not metabolize esculin, urea, meat, gelatin, casein, or nitrate. The G + C content is 56 to 57 mol%. DNA hybridization experiments did not reveal relatedness to phenotypically similar Clostridium strains. Strain 265 (= ATCC 49531) is the type strain.

Base Composition↗
PubMed1991

Paraproteinaemia in relatives of patients with primary acquired agammaglobulinaemia.

Two instances of the unusual familial association of severe primary acquired hypogammaglobulinaemia and paraproteinaemia are described, and previous reports of familial immunoglobulin dyscrasias are discussed. Our observations lend further support to the possible existence of a genetic predisposition to these disorders.

Agammaglobulinemia↗
PubMed1991

Coronavirus induced primary demyelination: indications for the involvement of a humoral immune response.

Coronavirus MHV-JHM infection of rodents can result in demyelinating encephalomyelitis. We analysed histological changes induced by coronavirus MHV-JHM infection in Lewis rats. Besides an acute disease (AE), chronic panencephalitis (CPE) and subacute demyelinating encephalomyelitis (SDE) were induced. These disease types were differentiated by the incubation period, the localization of lesions, the type of tissue damage and distribution of virus antigen. In AE and CPE, virus antigen was detected in neurons, astrocytes and oligodendrocytes, whereas in SDE neurons lacked virus antigen. Viral nucleocapsid protein (N) was present in the cytoplasm and the spike protein (S) was displayed on the surface of infected neural cells. However, expression of S protein relative to N protein was severely impaired in SDE lesions. Quantitative analysis of infiltrating inflammatory cells revealed that the number of macrophages and T cells were similar in lesions of AE, CPE and SDE. In contrast to that, SDE lesions contained a significantly higher number of IgG + B cells and plasma cells. In addition active demyelinating SDE lesions displayed an enhanced IgG content and deposits of complement C9. These results indicate that virus induced primary demyelination could be a consequence of antibody mediated cytotoxicity. Furthermore, a reduction in the number of cells producing spike protein in the chronic forms of the disease indicates down-regulation of this protein, possibly mediated by anti-S antibodies.

Animals↗
PubMed1991

Ultrasonography of urinary tract and micturition as an alternative to radiologic investigations in the spinal-cord-injured patient.

Over a period of 1.5 years (July 1989-Jan. 1991), a total of 504 patients, 442 of them suffering from spinal cord injuries with subsequent voiding disorders, were investigated by ultrasonography of the genitourinary tract. Ultrasonography of the upper urinary tract as well as the bladder and prostate provided and accurate image of the pathomorphological changes which go along with this kind of malfunction of the lower urinary tract in this group of patients. The application of rectal ultrasonography using a linear array rectal transducer was able to provide equal or even better images of the micturition process than micturition cystourethrography (MCU). An adequate and accurate real time image of the bladderneck, the prostatic urethra and the external rhabdosphincter could be obtained in all instances. Combined micturition cytourethrosonography (MCUS) with urodynamic evaluation has also been performed, which made the observation and judgement of the bladder outlet as well as the position of the catheter possible throughout the procedure without the interference of X-rays.

Adult↗
PubMed1990

Cellular mechanism of action of resiniferatoxin: a potent sensory neuron excitotoxin.

The mechanism of activation of sensory neurons by the potent irritant resiniferatoxin (RTX) was compared with that of the pungent compound, capsaicin. RTX and capsaicin evoked an inward, depolarising current associated with an increase in membrane conductance in a subpopulation of dissociated cultured neurons from rat dorsal root ganglia. RTX also evoked an uptake of 45Ca into and an efflux of [14C]guanidinium and of 86Rb from these cells but was at least 100-fold more potent than capsaicin. The levels of cGMP, but not cAMP were elevated by RTX. Prolonged exposure to RTX damaged DRG neurons by a predominantly osmotic process. RTX-sensitive cells were identified by a cobalt-staining method; neurofilament-containing DRG neurons were RTX-insensitive as were all sympathetic neurons and non-neuronal cells. Cultured DRG neurons from chick embryos were also unaffected by RTX. In a neonatal rat spinal cord-tail preparation in vitro, RTX activated capsaicin-sensitive peripheral nociceptive fibres and caused a subsequent spinal cord depolarization measured in the ventral spinal roots. Neither prolonged exposure to a phorbol ester, to desensitize/down-regulate protein kinase C, nor inhibition of protein kinase C by staurosporine affected responses produced by RTX or capsaicin. The effects of capsaicin were abolished when preparations were exposed to desensitizing concentrations of RTX. RTX therefore acts as a highly potent capsaicin analogue to activate a subpopulation of rat sensory neurons.

Animals↗
PubMed1990

[A registry of medullary thyroid cancer in West Germany].

A register for medullary thyroid carcinoma (MTC) in FRG has been set up by the "German Medullary Thyroid Carcinoma Study Group" in 1988. The aim is to provide a basis for collaborative work on MTC especially in the hereditary forms (i.e. multiple endocrine neoplasia [MEN] type IIa, IIb). For these hereditary varieties reliable screening tests exist and, if the disease is detected by family screening in an early stage, curative surgery is possible. Until now 408 patients (234 female, 174 male) with MTC have been reported by 17 cooperative centers. The mean age at diagnosis was 45.5 years. 25% (n = 104) are hereditary forms, most of them MEN IIa (n = 86), 13 are MEN IIb and 18 belong to the familial variety without other endocrinopathy. The mean age at diagnosis for MEN IIa was 36.5 years, MEN IIb 26.9 and for the pure familial form 27.5 years. As 33 patients per year have been diagnosed since 1982, nearly 25% of all expected cases of MTC in FRG have been registered.

Adult↗