PubMed Health⌕ Search

Biomedical subjects

J Winter

Publications and source records attributed to J Winter.

At least 19 recordsLinked to original sources
PubMed1992

Neurotoxic damage evokes regenerative responses from adult rat sensory neurones.

When adult rats were pre-treated systemically with the excitotoxin, capsaicin, a subset of their dorsal root ganglion (DRG) sensory neurones responded as if they had been axotomised. Firstly, an increased proportion of capsaicin-sensitive DRG neurones (identified by using a cobalt stain) vigorously extended processes in vitro. Additionally, a subset of small dorsal root ganglion neurones expressed elevated levels of the growth-associated protein-43 (GAP-43) in situ. Both vigorous neuritogenesis and elevated GAP-43 levels are characteristics of neurones that are actively regenerating following mechanical damage. Although capsaicin-treated adult DRG neurones show these regenerative responses, their C-fibers fail to regenerate in vivo.

Animals↗
PubMed1992

Regulation of expression of the neuronal POU protein Oct-2 by nerve growth factor.

POU proteins are a class of homeobox-containing transcription factors that regulate tissue-specific gene expression and influence cell differentiation and function. We have investigated the possible role of such factors in mediating the actions of nerve growth factor (NGF) on sensory neurons. NGF has been found to have differential effects on the levels of three POU protein transcription factors that are expressed in adult rat sensory neurons. A sensory neuron octamer-binding protein with the properties of the transcription factor Oct-2 is up-regulated 3-4-fold by NGF, as measured by mobility shift assays using nuclear extracts from adult rat dorsal root ganglion neurons grown in the presence or absence of NGF. Quantitation of Oct-2 mRNA by polymerase chain reaction amplification of RNA from such cells shows a parallel increase in Oct-2 mRNA levels. In contrast, the levels of mRNA encoding the ubiquitous POU protein Oct-1 or the neuron-specific POU protein Brn-3, also present in sensory neurons, are unaffected by NGF. These observations suggest a role for Oct-2 in mediating transcriptional effects induced by NGF. In particular, as Oct-2 is known to inhibit herpes simplex virus immediate-early gene expression in neuronal cells, these findings provide a mechanism for the known action of NGF in the maintenance of latent herpes virus infections in sensory neurons.

Animals↗
PubMed1992

Regional differences in the distribution of capsaicin-sensitive target-identified adult rat dorsal root ganglion neurons.

A retrograde labelling technique combined with a cobalt uptake assay in cultured adult rat dorsal root ganglion (DRG) neurons were applied to study the distribution of capsaicin sensitivity in relation to different peripheral targets. This study shows that there are regional differences between skin, skeletal muscle and urinary bladder; 20-30% of skin afferents, 40% of muscle afferents and 60% of bladder afferents were found to be capsaicin-senditive. This may reflect differences in the proportion of chemosensitive afferents innervating different peripheral tissues.

Animals↗
PubMed1992

Purification and characterization of benzoyl-CoA ligase from a syntrophic, benzoate-degrading, anaerobic mixed culture.

The benzoyl-CoA ligase from an anaerobic syntrophic culture was purified to homogeneity. It had a molecular mass of around 420 kDa and consisted of seven or eight subunits of 58 kDa. The temperature optimum was 37-40 degrees C, the optimum pH around 8.0 and optimal activity required 50-100 mM TRIS-HCl buffer, pH 8.0 and 3-7 mM MgCl2; MgCl2 in excess of 10 mM was inhibitory. The activation energy for benzoate was 11.3 kcal/mol. Although growth occurred only with benzoate as a carbon source, the benzoyl-coenzyme A (CoA) ligase formed benzoyl-CoA esters with benzoate, 2-, 3- and 4-fluorobenzoate, picolinate, nicotinate and isonicotinate. Acetate was activated to acetyl-CoA by an acetyl-CoA synthetase. The Km values for benzoate, 2-, 3- and 4-fluorobenzoate were 0.04, 0.28, 1.48 and 0.32 mM, the Vmax values 1.05, 1.0, 0.7 and 0.98 units (U)/mg, respectively. For reduced CoA (CoA-SH) a Km of 0.07 mM and a Vmax of 1.05 U/mg and for ATP a Km of 0.16 mM and a Vmax of 1.08 U/mg was determined. Benzoate activation was inhibited by more than 6 mM ATP, presumably by pyrophosphate generation from ATP. The inhibition constant (Ki) for pyrophosphate was 5.7 mM. No homology of the N-terminal amino acid sequence with that of a 2-aminobenzoyl-CoA ligase of a denitrifying Pseudomonas sp. was found.

Acetate-CoA Ligase↗
PubMed1992

Factors influencing local relapse and survival and results of salvage treatment after breast-conserving therapy in operable breast cancer: EORTC trial 10801, breast conservation compared with mastectomy in TNM stage I and II breast cancer.

A (modified) radical mastectomy (RM) was compared with breast-conserving therapy (BCT) in stage I and stage II breast cancer patients. Treatment of the study arm comprised lumpectomy, axillary clearance and radiotherapy to the breast (50 Gy in 5 weeks external irradiation and a boost with iridium implant of 25 Gy). 902 patients were included. There were 734 TNM stage II patients. Patients with microscopically incomplete excision of the tumour were not excluded. After a median follow-up of 6 years, overall survival and local recurrence rates do not differ significantly between the two study arms. Actuarial survival at 8 years was 73% after RM and 71% after BCT; actuarial local recurrence at 8 years was 9% and 15%, respectively. In the mastectomy group tumour size did not affect local relapse, but after BCT the incidence of local recurrences was higher for tumours of 2-5 cm (16%) than for smaller tumours (7%) (at 8 years, P = 0.08). Results of salvage treatment for local recurrence so far were similar in both the BCT and the mastectomy group.

Aging↗
PubMed1992

Transcutaneous cardiac pacing in patients with automatic implantable cardioverter defibrillators and epicardial patch electrodes.

In patients with automatic implantable cardioverter defibrillators, insulation of the epicardial patch electrodes (patches) prevents externally applied current from passing through the electrode to the cardiac muscle so that external transthoracic and even internal defibrillation can be unsuccessful. Because emergency cardiac pacing may be required in such a case, a study was performed to evaluate whether, and at what threshold and electrode orientation, transcutaneous pacing is possible in patients with implanted patches. Thresholds for transcutaneous pacing were determined during general anesthesia in nine patients with patches sewn across the heart (anterior right and posterior left ventricles) either before or after surgery, or at both times (automatic implantable cardioverter defibrillator implantation/exchange with or without coronary artery bypass grafting). Because surgery per se can increase the pacing threshold, nine patients of similar body size and weight undergoing routine coronary artery bypass grafting also were evaluated and served as a control group. Pacing thresholds (stimulus duration: 50 ms) were determined during normothermia with a transportable transcutaneous pacer, and adult cutaneous electrodes were placed across the patients' chest in the standard anteroposterior and right-to-left orientations. In all patients with patch electrodes, antero-posterior pacing was possible at a mean threshold of 73 +/- 30 mA standard deviation (range: 40-140 mA). This threshold was not significantly different (Mann-Whitney test) from that in control patients before (57 +/- 20 mA; range: 30-90 mA) or after (94 +/- 24 mA; range: 40-120 mA) coronary artery-bypass grafting. The surgical procedure per se significantly increased the threshold (Wilcoxon test, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Pacing, Artificial↗
PubMed1992

Immunologic findings in tissue of thyroid carcinoma.

We studied the occurrence of DR-antigen (DR-Ag) positive thyroid epithelial cells (TEC), lymphocyte (Ly)-subsets, and antigen-presenting cells (APC) in thyroid carcinoma and the influence of thyroid-stimulating hormone (TSH) on immunologic behavior. Tissue slices from various thyroid carcinomas (n = 14) and endemic goiters (n = 12) were investigated by immunohistochemical methods (PAP/APAAP/FITC) using monoclonal antibodies (MoAbs) against DR-Ag, dendritic cells (APC), endothelial cells, CD-3 Ly, CD-4 Ly, and CD-8 Ly. Monolayers of TEC were cultured in the presence or absence of TSH (0.01 mU/ml) and/or PHA (0.1 mg/ml) over 24 h and screened for DR-Ag expression. Various ranges of DR-Ag expression were detectable in 13 thyroid carcinomas. One thyroid carcinoma and all endemic goiters were DR-Ag-. The amount of APC and local infiltrating Ly correlated very well with the presence and intensity of DR-Ag+ TEC. The lymphocytic CD-4/CD-8 ratio varied in a wide range. No prevalence of Ly-distribution for any type of carcinoma was found. PHA induced DR-Ag expression in all thyroid carcinomas and endemic goiters. This effect was enhanced significantly by TSH. DR-Ag expression on thyroid carcinoma cells may be considered as an immune activating factor. These "neoantigens" may be induced by lymphokines released by the local immune competent cells. The distribution of Ly and DR-Ag+ TEC in thyroid carcinoma seems to represent the individual immunologic response against the tumor. Whether TSH acts as an immune modulator directly or indirectly, as described elsewhere, cannot be concluded from these results.

Antigens, Neoplasm↗
PubMed1992

Randomized clinical trial to assess the value of breast-conserving therapy in stage I and II breast cancer, EORTC 10801 trial.

In a prospective randomized clinical trial conducted by the European Organization for Research and Treatment of Cancer (EORTC), mastectomy was compared with breast-conserving therapy in 903 stage I and stage II breast cancer patients entering the study between 1980 and 1986. The main participating centers were: Guy's Hospital, London; The Netherlands Cancer Institute, Amsterdam; University Hospital, Leuven; Radiotherapy Institute, Rotterdam; Breast Unit, Tijgerberg, S.A. The data were collected in the EORTC Data Center, Brussels. Treatment in the study arm consisted of lumpectomy, axillary clearance, and radiotherapy to the breast (50 Gy external irradiation in 5 weeks followed by boost with iridium implant of 25 Gy). Important in this study is the large number of TNM stage II patients (755). Most patients were stage II because of the size of the tumor (2-5 cm). The patient and tumor characteristics in the study and control groups were well balanced. So far the survival curves and local recurrence rates are not statistically different for the two study arms. Tumor size was found in univariate analysis to be a significant risk factor for local recurrence in the breast-conserving therapy group but not in the mastectomy group. Results of salvage treatment for local recurrence were not better for the breast-conserving therapy group compared with the mastectomy group. Measurements of quality of life and cosmesis show a clear benefit for the breast-conserving therapy group.

Adult↗
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↗