Search PubMed⌕ Search

Biomedical subjects

J Winter

Publications and source records attributed to J Winter.

At least 109 records · Page 6Linked to original sources

Influence of inflammation or disconnection from peripheral target tissue on the capsaicin sensitivity of rat dorsal root ganglion sensory neurones.

Dorsal root ganglion (DRG) sensory neurones from adult rats are known to lose their capsaicin sensitivity in vitro if they are cultured without nerve growth factor (NGF). Here we show similar results following peripheral nerve transection in vivo, which deprives DRG sensory neurones of target-derived NGF. By measuring capsaicin-stimulated 45Ca uptake into DRG neurones which had been briefly cultured, capsaicin sensitivity was shown to decrease in neurones whose axons had been previously severed in vivo. Conversely, during experimental inflammation of the rat paw, there is an increase in the supply of NGF to neurones innervating the inflamed area. In this case, however, no significant increase in capsaicin sensitivity could be demonstrated in briefly cultured neurones which had previously innervated an inflamed limb. This suggests that expression of capsaicin sensitivity in DRG is maximal at levels of NGF found in normal animals.

Animals↗

Activation and degradation of benzoate, 3-phenylpropionate and crotonate by Syntrophus buswellii strain GA. Evidence for electron-transport phosphorylation during crotonate respiration.

A strictly anaerobic, benzoate-degrading bacterium, Syntrophus buswellii strain GA, was able to degrade benzoate or 3-phenylpropionate to acetate, CO2 and H2, if the hydrogen partial pressure was sufficiently low. The hydrogen was removed in syntrophic coculture by Methanospirillum hungatei or by Desulfovibrio sp. through interspecies hydrogen transfer or in pure culture by the use of crotonate as reducible cosubstrate. Alternatively, S. buswellii strain GA could grow in pure culture with crotonate. Activities of seven catabolic enzymes were measured in crude cell extracts of S. buswellii strain GA grown with various substrates and of crotonate-grown S. buswellii strain DSM 2612A. Benzoate, 3-phenylpropionate and crotonate were activated by CoA ligases. Glutaryl-CoA dehydrogenase was found to be involved in the degradation of aromatic compounds and enzymes catalysing beta-oxidation were involved in the reaction sequence from crotonyl-CoA to acetate. A c-type cytochrome was present in the cytoplasm, whereas b-type cytochromes were associated with the membranes of both S. buswellii strains grown on crotonate. These indicated the presence of an electron-transport system. A high growth yield of crotonate-grown S. buswellii strain GA might be explained by electron-transport phosphorylation in addition to substrate-level phosphorylation.

Bacteria, Anaerobic↗

K252a modulates the expression of nerve growth factor-dependent capsaicin sensitivity and substance P levels in cultured adult rat dorsal root ganglion neurones.

K252a, an inhibitor of trk phosphorylation and nerve growth factor signal transduction in PC12 cells, blocked nerve growth factor-induced responses in cultured adult rat dorsal root ganglion sensory neurones. The nerve growth factor-dependent appearance of capsaicin sensitivity and accumulation of the neuropeptide substance P were inhibited when dorsal root ganglion neurones were grown in the presence of low concentrations (100 nM) of K252a. At higher concentrations (3 microM), however, K252a stimulated the development of capsaicin sensitivity and the accumulation of substance P even in the absence of nerve growth factor. By using a wide dose range, therefore, we showed that K252a could either inhibit or mimic nerve growth factor's actions on sensory neurones. These results may explain the apparent paradox in the literature that some groups show a blocking effect of K252a on nerve growth factor-dependent survival of dorsal root ganglion sensory neurones, whereas other report that K252a can substitute for nerve growth factor or other trophic factors and promote neuronal survival.

Animals↗

Isolation and characterization of a new gram-negative, acetone-degrading, nitrate-reducing bacterium from soil, Paracoccus solventivorans sp. nov.

An acetone-degrading, nitrate-reducing, coccoid to rod-shaped bacterium, strain L1, was isolated from soil on the site of a natural gas company. Cells of the logarithmic growth phase reacted gram positive, while those of the stationary growth phase were gram negative. Single organisms were 0.4 to 0.5 by 0.9 to 1.5 microns in size, nonmotile, and non-spore forming and had poly-beta-hydroxybutyrate inclusions. The doubling time of strain L1 on acetone-CO2-nitrate at the optimal pH of 7 to 8 and the optimal temperature of 30 to 37 degrees C was 12 h. More than 0.2% NaCl or 10 mM thiosulfate inhibited growth. For oxygen or nitrate respiration, acetone and a few organic chemicals were utilized as carbon sources whereas many others could not be used (for details, see Results). Bicarbonate (or CO2) was essential for growth on acetone but not for growth on acetoacetate. The growth yields for acetone-CO2 and acetoacetate were 28.3 and 27.3 g/mol, respectively. With acetone as the carbon source, poly-beta-hydroxybutyrate accounted for up to 40% of the cellular dry weight. The DNA of strain L1 had a G + C content of 68.5 mol% (as determined by high-performance liquid chromatography of nucleotides) or 70 mol% (as determined by the TM method). The sequence of the gene coding for the 16S rRNA led to the classification of strain L1 in the paracoccus group of the alpha subclass of the Proteobacteria. The new isolate is named Paracoccus solventivorans sp. nov. DSM 6637.

Acetone↗

Anaerofilum pentosovorans gen. nov., sp. nov., and Anaerofilum agile sp. nov., two new, strictly anaerobic, mesophilic, acidogenic bacteria from anaerobic bioreactors.

Strictly anaerobic, gram-positive, nonsporing, thin rod-shaped organisms whose cells were 0.2 to 0.6 by 3 to 6 microns were isolated from a Hoechst Biohochreaktor (strain FaeT [T = type strain]) and from the biofilm population of a fixed-film reactor treating sour whey (strain FT). Strain FT was vigorously motile during early logarithmic growth by means of peritrichously inserted flagella, while strain FaeT was seldom motile and usually possessed no flagella. During the stationary growth phase both strains formed spheroplasts. The temperature optimum was close to 37 degrees C (temperature range for growth, > or = 17 to < 45 degrees C) and the pH optimum was 7.0 to 7.4 (pH range, 6.5 to 8.0) for both strains. The two organisms grew chemoorganotrophically on a number of mono- and disaccharides, including glucose and xylose; yeast extract was required for growth. The principal fermentation products from glucose included lactate, acetate, ethanol, formate, and CO2. Hydrogen was not generated. The G + C contents of the DNAs of strains FaeT and FT were 55 and 54.5 mol%, respectively. The cell wall architecture was typical of gram-positive bacteria; the cells had an extraordinarily thin type A3 alpha' peptidoglycan layer containing muramic acid. Analysis of 16S ribosomal DNA sequences of the two new isolates demonstrated that they represent members of a new genus of bacteria in Clostridium cluster IV of the domain Bacteria and that the misclassified organism Fusobacterium prausnitzii and Clostridium leptum are among their closest relatives. The names Anaerofilum pentosovorans gen. nov., sp. nov. (type strain, strain Fae [= DSM 7168]) and Anaerofilum agile sp. nov. (type strain, strain F [= DSM 4272]) are proposed.

Anaerobiosis↗

-Congenital hypoplasia of the anterior tricuspid leaflet as a cause of high-grade tricuspid valve insufficiency in a 64-year-old patient-.

In a 64-year-old man a heart murmur was present since childhood and could be identified 8 years ago as isolated tricuspid regurgitation. Because of progressive dyspnea there was an indication for surgical treatment. Intraoperatively, we found a hypoplastic anterior leaflet, though the other two leaflets were preserved in totally good condition, without any evidence of endocarditis. Tricuspid valve replacement was performed as there was no chance of reconstruction. To our knowledge, this is the first description of a congenital hypoplastic anterior leaflet of the tricuspid valve.

Cardiomegaly↗

[Geriatric tumor surgery--change in the patient sample].

The comparison of our surgical tumor patients over 65 years of age treated in 1973-1974 or 1993-1994 showed the following results: increased average age and more patients with a greater unfavorable preoperative risk profile, an increase in colorectal tumors, a decrease in gastric carcinomas, no changes in tumor stages, more frequent sphincter-preserving operations for rectal tumors, an increase in the curative resection rate, lower mortality and shorter hospital stays. A curative resection of a malignant tumor is justified in the majority of elderly patients and should be performed considering the post-operative quality of life.

Aged↗

The effect of inhibitors on the growth of the entomopoxvirus from Amsacta moorei in Lymantria dispar (gypsy moth) cells.

Within the family of Poxviridae, the entomopoxviruses are the most distant relatives of the more well-known and intensively studied orthopoxviruses (vaccinia and variola). The growth of the entomopoxvirus from Amsacta moorei (AmEPV) has been characterized in cell culture and compared to that of vaccinia virus (VV), the prototypic orthopoxvirus. The overall characteristics of infected cell cultures were generally similar between the two viruses. One striking difference noted was the apparent absence of proteolytic processing of late AmEPV viral proteins, a hallmark of vertebrate poxvirus infections associated with viral morphogenesis. AmEPV, like VV, was found to be sensitive to all the inhibitors of viral infection tested including phosphonoacetic acid, 1-beta-D-arabinofuranosylcytosine, and isatin-beta-thiosemicarbazone (IBT), a compound associated with the rather specific inhibition of vertebrate poxviruses. While both VV and AmEPV are inhibited by IBT, the inhibition of AmEPV, unlike that of VV, is not accompanied by either a breakdown of ribosomal RNA or a global inhibition of late viral protein synthesis. Instead, in the presence of IBT, AmEPV enveloped, immature virions form devoid of a well-differentiated core, which unlike mature virions fail to insert into occlusion bodies.

Animals↗

A minimal CGRP gene promoter is inducible by nerve growth factor in adult rat dorsal root ganglion neurons but not in PC12 phaeochromocytoma cells.

The calcitonin/CGRP gene is transcribed in thyroid C cells and some neuronal cells but not in other cell types. Although the promoter sequences mediating gene activity in thyroid C cells have been extensively studied, the elements responsible for promoter activity in neuronal cells and its stimulation by nerve growth factor (NGF) have not previously been defined. We report the first use of the calcium phosphate procedure to successfully transfect adult rat dorsal root ganglion neurons, which naturally express the calcitonin/calcitonin gene-related peptide (CGRP) in an NGF-inducible manner. This method was used to characterize the elements in the calcitonin/CGRP promoter which are responsible for its basal activity and NGF inducibility in DRG neurons and in PC12 cells, a neuronally derived cell line which does not naturally express the calcitonin/CGRP gene. Although the sequences required for basal activity are similar in each cell type, we show that a minimal calcitonin/CGRP promoter is NGF-responsive in dorsal root ganglion cells, but that upstream sequences are required for such inducibility in PC12 cells.

Animals↗

Nerve growth factor induces the Oct-2 transcription factor in sensory neurons with the kinetics of an immediate-early gene.

The Oct-2 transcription factor has a predominantly inhibitory effect on gene expression in neuronal cell lines. This factor and its corresponding mRNA have previously been shown to be elevated in adult rat dorsal root ganglion (DRG) neurons chronically exposed to nerve growth factor (NGF). Here we show that the Oct-2 mRNA is rapidly induced in DRG cells exposed to NGF and that such induction still occurs to a lesser extent in the presence of the protein synthesis inhibitor cycloheximide. These findings characterize Oct-2 as a novel member of the immediate-early class of NGF-induced transcription factors whose previously defined members have a predominantly stimulatory effect on the expression of other genes. Induction of the Oct-2 mRNA was also observed in DRG neurons treated with acidic fibroblast growth factor or epidermal growth factor but not with a range of other growth factors and neurotrophins. The role of the Oct-2 transcription factor in mediating the response of DRG neurons to NGF is discussed.

Animals↗

[Primary seminoma. A rare mediastinal tumor].

This is a report on three patients with primary mediastinal seminoma. Two patients had no symptoms, and one had had thoracic pain for the last few years. The preoperative diagnosis was thymoma in all cases, and in one patient the radiologist had suspected a seminoma. We removed the tumor after performing median sternotomy (n = 2) and anterolateral left thoracotomy (n = 1). The presence of a primary gonadal seminoma was excluded with a urological and ultrasound examination. All patients are still alive following adjuvant chemotherapy (n = 2; 120 and 8 months) and radiotherapy (n = 1; 84 months). Chemotherapy consisted of four cycles of cisplatin, etoposide and ifosfamide or combination therapy with cisplatin, bleomycin and velbe.

Adult↗

Contribution of interleukin-1 beta to the inflammation-induced increase in nerve growth factor levels and inflammatory hyperalgesia.

1. Peripheral inflammation is associated with the local production of neuroactive inflammatory cytokines and growth factors. These may contribute to inflammatory pain and hyperalgesia by directly or indirectly altering the function or chemical phenotype of responsive primary sensory neurones. 2. To investigate this, inflammation was produced by the intraplantar injection of complete Freund's adjuvant (CFA) in adult rats. This resulted in a significant elevation in interleukin-1 beta (IL-1 beta) and nerve growth factor (NGF) levels in the inflamed tissue and of the peptides, substance P and calcitonin gene-related peptide (CGRP) in the L4 dorsal root ganglion 48 h post CFA injection. 3. The effects of a steroidal (dexamethasone) and a non-steroidal (indomethacin) anti-inflammatory drug on the levels of NGF and IL-1 beta in inflamed tissue were investigated and compared with alterations in behavioural hyperalgesia and neuropeptide expression in sensory neurones. 4. Systemic dexamethasone (120 micrograms kg-1 per day starting the day before the CFA injection) had no effect on the inflammatory hyperalgesia. When the dose was administered 3 times daily, a reduction in mechanical and to a lesser extent thermal sensitivity occurred. Indomethacin at 2 mg kg-1 daily (i.p.) had no effect on the hyperalgesia and a dose of 4 mg kg-1 daily was required to reduce significantly mechanical and thermal hypersensitivity. 5. The increase in NGF produced by the CFA inflammation was prevented by both dexamethasone and indomethacin, but only at the higher dose levels. Dexamethasone at the lower and higher dose regimes diminished the upregulation of IL-1 beta whereas indomethacin had an effect only at the higher dose. 6. The increase in SP and CGRP levels produced by the CFA inflammation was prevented by dexamethasone and indomethacin at the lower and higher dose regimes. 7. Intraplantar injections of IL-1 beta (0.01, 0.1 and 1 ng) produced a brief (6 h) thermal hyperalgesia and an elevation in cutaneous NGF levels which was prevented by pretreatment with human recombinant IL-1 receptor antagonist (IL-1 ra) (0.625 microgram, i.v.). The thermal hyperalgesia but not the NGF elevation produced by intraplantar IL-1 beta (1 ng) was prevented by administration of a polyclonal neutralizing anti-NGF serum. 8. IL-1 ra significantly reduced the mechanical hyperalgesia produced by CFA for 6 h after administration as well as the CFA-induced elevation in NGF levels. Anti-NGF pretreatment substantially reduced CFA-induced mechanical and thermal hyperalgesia without reducing the elevation in IL-1 beta. 9. Intraplantar NGF (0.02, 0.2 and 2 microg) injections produced a short lasting thermal and mechanical hyperalgesia but did not change IL-1beta levels in the hindpaw skin.10. Our results demonstrate that IL-1beta contributes to the upregulation of NGF during inflammation and that NGF has a major role in the production of inflammatory pain hypersensitivity.

Animals↗

[Adrenal incidentaloma].

Asymptomatic adrenal tumors are discovered more and more frequently with improving quality of diagnostic imaging. Treatment of these tumors, described as incidentalomas is controversial and depends on the one hand on the size of the tumor and on the other hand on morphological appearance in diagnostic imaging. In the literature a tumor size over 3 cm is in general regarded as an indication for operation, based on findings of Copeland et al. where the size of the tumor was correlated with malignancy. In the Department of Surgery in Mannheim 28 operations on adrenal incidentalomas have been performed between 1973-1993. In three patients a carcinoma was found. Four of the removed tumors each of them benign had a diameter smaller than three centimeters. An operation seems to be justified under certain conditions, even in small tumors, because potentially malignant tumors can undergo early and radical surgery. A general recommendation for treatment of the above mentioned tumors, depending only on size and morphology in diagnostic imaging, seems to be difficult. The decision for surgical therapy needs to be evaluated individually for every patient.

Adrenal Gland Neoplasms↗

[Results of surgical therapy of early stomach cancer].

Between 1972 and 1993 232 patients with early gastric cancer have been resected at the Surgical University Hospital of Mannheim. At the time of surgery 9.9% of the patients had lymph node involvement, 2 of them had distant metastases. In 59.9% of the cases (n = 138) a subtotal distal gastric resection, in 34.1% (n = 79) a total gastrectomy and in 6.4% (n = 15) a proximal or an atypical resection were performed. Following distal resection and total gastrectomy a radical lymphadenectomy of the compartments I and II was performed. The hospital lethality was 5.2%, the morbidity 18.1%. There were no statistical significant differences between the different surgical methods. The cumulative-5-year-survival rate was 80% without any statistically significant differences between the surgical methods and the histological types according to the Japanese classification of early gastric cancer.

Female↗