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Biomedical subjects

M Fischer

Publications and source records attributed to M Fischer.

At least 55 records · Page 3Linked to original sources
PubMed2001

Biosynthesis of riboflavin.

The biosynthesis of one riboflavin molecule requires one molecule of GTP and two molecules of ribulose 5-phosphate. The imidazole ring of GTP is hydrolytically opened, yielding a 4,5-diaminopyrimidine that is converted to 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione by a sequence of deamination, side chain reduction, and dephosphorylation. Condensation of 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione with 3,4-dihydroxy-2-butanone 4-phosphate obtained from ribulose 5-phosphate affords 6,7-dimethyl-8-ribityllumazine. Dismutation of the lumazine derivative yields riboflavin and 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione, which is recycled in the biosynthetic pathway. Two reaction steps in the biosynthetic pathway catalyzed by 3,4-dihydroxy-2-butanone 4-phosphate synthase and riboflavin synthase are mechanistically very complex. The enzymes of the riboflavin pathway are potential targets for antibacterial agents.

Bacillus subtilis↗
PubMed2001

Meningococcal vaccines.

Global control and prevention of meningococcal disease depends on the further development of vaccines that overcome the limitations of the current polysaccharide vaccines. Protein-polysaccharide conjugate vaccines likely will address the marginal protective antibody responses and short duration of immunity in young children derived from the A, C, Y, and W-135 capsular polysaccharides, but they will be expensive to produce and purchase, and may not offer a practical solution to the countries with greatest need. In addition, OMP vaccines have been tested extensively in humans and hold some promise in the development of a serogroup B vaccine, but are limited by the antigenic variability of these subcapsular antigens and the resulting strain-specific protection. Elimination of meningococcal disease likely will require a novel approach to vaccine development, ideally incorporating a safe and effective antigen or antigens common to all meningoccocal serogroups. As a solely human pathogen, however, N. meningitidis has developed many tools with which to evade the human immune system, and likely will pose a formidable challenge for years to come.

Adolescent↗
PubMed2001

Extended hepatic resection: a 6-year retrospective study of risk factors for perioperative mortality.

BACKGROUND: Extended hepatic resection (more than four liver segments) is a major operative procedure that is associated with significant risk. The purpose of this study was to assess the impact of perioperative variables on in-hospital mortality after extended hepatectomy. STUDY DESIGN: Consecutive patients who underwent extended hepatic resection were studied. The prognostic value of 29 perioperative variables was evaluated using in-hospital mortality as the endpoint. For each variable, the odds ratio (95% confidence interval) for in-hospital mortality was calculated. Those variables with a lower confidence limit > 1 were considered important risk factors. The population was stratified into categories of patients having the same number of risk factors, and mortality was estimated for each group. These data were used to develop a risk assessment algorithm. RESULTS: There were 14 deaths (6%) in 226 patients. Three preoperative variables (cholangitis, creatinine > 1.3 mg/dL, and total bilirubin > 6 mg/dL) and two operative variables (blood loss > 3 L and vena caval resection) appear to be important factors for in-hospital mortality. The mortality associated with the presence of any two of the five factors was 100% (5 of 5), and the mortality associated with the absence of these factors was 3% (6 of 191). CONCLUSIONS: Perioperative evaluation of patients undergoing extended hepatic resection should include the quantitation of mortality risk factors. The combination of any two factors among preoperative cholangitis, elevated serum creatinine, elevated serum bilirubin, high operative blood loss, and vena cava resection may carry a high mortality risk. These results require prospective validation.

Adolescent↗
PubMed2001

Enzymatic extractability of soybean meal proteins and carbohydrates: heat and humidity effects.

To study the incomplete enzymatic extractability of proteins and carbohydrates of thermally treated soybean meals, one unheated and three heat-treated soybean meals were produced. To obtain truly enzyme-resistant material, the meals were extracted by a repeated hydrolysis procedure using excessive concentrations of different combinations of commercial protease and carbohydrase preparations. The water extractability of protein from the different meals varied considerably (13-67%). For all soybean meals, enzymatic treatment extracted most of the original protein (89-94%). Carbohydrase preparations did not improve protein extraction. High-humidity heat treatment led to a more effective enzymatic extraction, which seemed to correlate with the extent of protein denaturation. Results with purified proteins indicated that the soybean meal matrix affects the enzymatic extraction of protein from the meals. Interactions between protein and other components (e.g., cellulose) may explain the incomplete enzymatic extractability of protein from the meals.

Carbohydrate Metabolism↗
PubMed2001

The role of complement in inflammation and adaptive immunity.

Major advances in our understanding of the immunobiology of complement were made within the past 5 years primarily due to the development of gene-targeting technology. New strains of mice bearing specific deficiencies in serum complement proteins or their receptors were developed using this approach. Characterization of these mice has provided new and exciting insights into the biology of the complement system. In this review, we discuss recent results on two important aspects of the complement system, i) host protection and inflammation, and ii) regulation of B lymphocytes of adaptive immunity. While these two roles appear distinct, they are linked. We discuss how natural antibody and classical pathway complement work together in host protection against bacterial infection on the one hand but, on the other, they co-operate to induce inflammation as observed in reperfusion injury. Significantly, the lymphocytes that produce natural antibody, the B-1 lymphocytes, are regulated in part by the complement system.

Animals↗
PubMed2001

Diagnostic impact and sensitivity of skin biopsies in Sneddon's syndrome. A report of 15 cases.

BACKGROUND: Sneddon's syndrome is defined as a combination of idiopathic livedo racemosa generalisata and symptoms of cerebrovascular defect. The disease usually starts with vascular symptoms in the epidermis, with neurological deficits becoming evident later. For this reason, histological examination of skin biopsies and determination of arteriolar occlusion is of particular importance for reliable categorization and early diagnosis. To date, these methods have been considered to be too insensitive. OBJECTIVES: To evaluate the sensitivity of skin biopsies in Sneddon's syndrome. METHODS: We took a total of five deep punch biopsies (4 mm) from different areas of the livedo (three from white and two from red areas) in 15 patients. Present knowledge of the pathogenic relationships and the particular anatomical features of the skin were taken into account. RESULTS: The method had a sensitivity of 27% with one biopsy, 53% with two biopsies and 80% with three biopsies taken from white areas in all cases. CONCLUSIONS: Skin biopsies using the method presented achieved a high sensitivity, suggesting that the diagnosis in clinically suspected cases could be confirmed in the majority of cases with this technique.

Adolescent↗
PubMed2001

Mast cells express functional CD30 ligand and are the predominant CD30L-positive cells in Hodgkin's disease.

Hodgkin's disease (HD) tumours are characterized by the presence of few tumour cells, the Hodgkin and Reed-Sternberg (HRS) cells, surrounded by a large amount of non-neoplastic cells. The role of this cell infiltrate for the development of HD is not known. CD30, belonging to the tumour necrosis factor receptor superfamily, is highly expressed on HRS cells and believed to be involved in tumourigenesis and tumour progression. Tumour samples from 42 patients were immunohistochemically double-stained for tryptase, a mast cell-specific proteinase and CD30 ligand (CD30L). Tryptase-positive mast cells were present in all tumours. Of these cells, 50% expressed CD30L and 66% of the CD30L-positive cells were mast cells. CD30L mRNA in in vitro developed normal mast cells and malignant human and murine mast cell lines was detected using reverse transcription polymerase chain reaction. CD30L protein expressed on human mast cells was detected using flow cytometry. In a co-culture assay, the human mast cell line HMC-1 stimulated thymidine uptake in HRS cell lines, and the stimulation could be blocked using CD30L-specific monoclonal antibodies. In conclusion, mast cells are present in HD tumours and are the predominant CD30L-expressing cells. CD30L-CD30 interaction is a pathway by which mast cells may stimulate DNA synthesis in HRS cells.

Adult↗
PubMed2001

Genetic structure of the annual weed Senecio vulgaris in relation to habitat type and population size.

Throughout the world, the highly selfing annual common groundsel, Senecio vulgaris (Asteraceae) is a common weed. Recently, it has also colonized ecological compensation areas in agro-ecosystems. We investigated the genetic structure of S. vulgaris using random amplified polymorphic DNA (RAPD) profiles of 80 plants from nine populations representing three habitat types in two regions in Switzerland. RAPD variation among regions (19.8%), among populations within regions (19.2%) and within populations (61.1%) was highly significant (ANOVA; P < 0.001). Gene flow estimated from the observed differentiation among populations (PhiST = 0.382) was low (assuming Wright's island model, Nem = 0.404). Genetic distances between pairs of populations were significantly correlated with geographical distances (Mantel test; r = 0.37, P < 0.03). Molecular variance obtained with AMOVA was lowest in the small populations in compensation areas (1.13), intermediate in vineyard populations (2.49), all located in northern Switzerland and highest in the larger vegetable field populations from western Switzerland (3.41; P < 0.05). Overall, there was a positive correlation of molecular variance and population size (P < 0.05), as expected under genetic drift. However, molecular variance was negatively correlated with population size among populations in ecological compensation areas, suggesting that selection was also important. We also applied triazine herbicide to leaves of three offspring of each of the 80 plants. Plants from populations of compensation areas showed higher mean levels and reduced variation in the resistance to triazine herbicide than plants from vineyards and vegetable fields. This suggests that compensation areas were colonized from adjacent corn fields, in which there has been selection for herbicide resistance. We discuss the implications of our results for the biological control of S. vulgaris.

Drug Resistance↗
PubMed2001

KP4 fungal toxin inhibits growth in Ustilago maydis by blocking calcium uptake.

KP4 is a virally encoded fungal toxin secreted by the P4 killer strain of Ustilago maydis. From our previous structural studies, it seemed unlikely that KP4 acts by forming channels in the target cell membrane. Instead, KP4 was proposed to act by blocking fungal calcium channels, as KP4 was shown to inhibit voltage-gated calcium channels in rat neuronal cells, and its effects on fungal cells were abrogated by exogenously added calcium. Here, we extend these studies and demonstrate that KP4 acts in a reversible manner on the cell membrane and does not kill the cells, but rather inhibits cell division. This action is mimicked by EGTA and is abrogated specifically by low concentrations of calcium or non-specifically by high ionic strength buffers. We also demonstrate that KP4 affects (45)Ca uptake in U. maydis. Finally, we show that cAMP and a cAMP analogue, N 6,2'-O-dibutyryladenosine 3':5'-cyclic monophosphate, both abrogate KP4 effects. These results suggest that KP4 may inhibit cell growth and division by blocking calcium-regulated signal transduction pathways.

Antifungal Agents↗
PubMed2001

Soluble gp130 is the natural inhibitor of soluble interleukin-6 receptor transsignaling responses.

Signal transduction in response to interleukin-6 (IL-6) requires binding of the cytokine to its receptor (IL-6R) and subsequent homodimerization of the signal transducer gp130. The complex of IL-6 and soluble IL-6R (sIL-6R) triggers dimerization of gp130 and induces responses on cells that do not express membrane bound IL-6R. Naturally occurring soluble gp130 (sgp130) can be found in a ternary complex with IL-6 and sIL-6R. We created recombinant sgp130 proteins that showed binding to IL-6 in complex with sIL-6R and inhibited IL-6/sIL-6R induced proliferation of BAF/3 cells expressing gp130. Surprisingly, sgp130 proteins did not affect IL-6 stimulated proliferation of BAF/3 cells expressing gp130 and membrane bound IL-6R, indicating that sgp130 did not interfere with IL-6 bound to IL-6R on the cell surface. Additionally, sgp130 partially inhibited proliferation induced by leukemia inhibitory factor (LIF) and oncostatin M (OSM) albeit at higher concentrations. Recombinant sgp130 protein could be used to block the anti-apoptotic effect of sIL-6R on lamina propria cells from Crohn disease patients. We conclude that sgp130 is the natural inhibitor of IL-6 responses dependent on sIL-6R. Furthermore, recombinant sgp130 is expected to be a valuable therapeutic tool to specifically block disease states in which sIL-6R transsignaling responses exist, e.g. in morbus Crohn disease.

Acute-Phase Reaction↗
PubMed2001

Dapsone in rosacea fulminans.

Rosacea fulminans is a rare disease with female predominance characterized by abrupt onset of pustules, papules, and confluent nodules on the face. The conventional treatment consists of systemic glucocorticoids and isotretinoin. We present the case of a 56-year-old woman with a marked facial papulopustular eruption that had followed an initial period of severe seborrhoea. Conventional treatment produced no clear improvement. Dapsone treatment achieved complete healing in 5 weeks.

Administration, Oral↗
PubMed2001

Long-term effects of in-hospital cardiac rehabilitation on the cardiac risk profile. A case-control study in pairs of siblings with myocardial infarction.

AIMS: In the general population, measures for secondary prevention of myocardial infarction are poorly utilized. Our aim was therefore to analyse whether post-myocardial infarction in-hospital rehabilitation and education programmes improve the subsequent utilization of preventive strategies. METHODS AND RESULTS: We screened 93 500 patient charts in cardiac rehabilitation clinics to identify a myocardial infarction patient with a sibling, who likewise had a myocardial infarction prior to the age of 60 years but was discordant with respect to the participation in cardiac in-hospital rehabilitation. In 92 such sibling pairs the coronary risk profile was studied by standardized questionnaire, biochemical measurements and physical examination. At the time of the acute myocardial infarction, both groups showed an equal risk factor distribution. However, at follow-up (on average 5.5 years after myocardial infarction), rehabilitation-siblings presented with significantly lower systolic (137+/-2 vs 150+/-3 mmHg, P<0.01) and diastolic blood pressure (82+/-1 vs 89+/-1 mmHg, P<0.01). Antihypertensive drug therapy resulted more often in effective (<or=140/90 mmHg) control of blood pressure (58% vs 29%, P<0.01). Blood lipid levels and smoking prevalence tended to be lower in rehabilitation-siblings. Significantly fewer rehabilitation-siblings presented with two or more modifiable risk factors (OR 0.36 (CI 0.17-0.76); P<0.01). There was a strong tendency towards fewer recurrent cardiac events (re-myocardial infarction, coronary angioplasty, coronary artery bypass grafting) during follow-up in rehabilitation-siblings (OR 0.57 (CI 0.31-1.04); P=0.07). CONCLUSION: An in-hospital programme for cardiac rehabilitation may successfully encourage therapy to modify risk factors and thus enhance the long-term implementation of secondary prevention.

Case-Control Studies↗
PubMed2001

[Long-term results of radium contact irradiation of laryngeal carcinoma and their relevance in modern therapeutical regimens].

BACKGROUND: Despite the fact that it is widely accepted that a second radiogenic carcinoma might occur after radiotherapy of laryngeal carcinomas, there are only a few long-term follow-up studies published yet. METHODS: Between 1973 and 1988 193 patients have been treated by radium contact irradiation because of glottic cancer (Tcis, T1, T2). After the cancer had been diagnosed by biopsy, a partial resection of the thyroid cartilage in the shape of a window 16 x 18 mm was carried out and a self-retaining capsule which harbours the radium was brought into position. RESULTS: 190 (181 men and 9 women) out of 193 patients could be followed up. At the time of investigation 109 patients had already died, 66 intercurrently. The actuarial disease free survival rate 5 and 10 years for Tcis/T1 glottic cancers were 84.6% and 83.6%. For T2 carcinomas a rate of 100% was found respectively. The actuarial overall survival rate was 96.8% after 5 and 93.1% after 10 years for Tcis/T1 carcinomas. The T2 carcinomas revealed an actuarial overall survival rate of 100% after 5 and 10 years. CONCLUSIONS: As the results of radium contact irradiation are not better than those which can be achieved by microsurgery or modern irradiation techniques no indication exists for a radium contact irradiation of glottic laryngeal cancer today.

Adult↗
PubMed2001

[Cochlear implantation: relationship between speech development and insertion depth in children].

BACKGROUND: The goal in pediatric cochlear implantation is improved hearing leading to better speech development, which may allow their integration into mainstream schools. Whether the intracochlear position of the electrode array has an influence on speech development or not is controversially discussed. PATIENTS: Between 1996 and 1998 29 children ranging from 1.5 to 11.8 years (median 4 years) were provided with a Nucleus 22M or 24M cochlear implant system. Speech and language skills were assessed by a closed-set test (Mainzer test) and by the Schmid-Giovannini score for hearing development pre-implantation and at 6, 12, 18 and 24 months post-implantation. The position of the electrode array was determined by the surgical record and by a postoperative transorbital x-ray. Since the promontory has a thickness of one to two electrode bands, we defined deep insertion as more than 24 bands intracochlear. RESULTS: The patients were divided into 2 groups according to the insertion depth: Group 1 (n = 8) 24 bands (22 electrodes and 2 stiffening rings correspond to < or = 18 mm) or less and group 2 (n = 21) more than 24 bands intracochlear correspond to > 18 mm). The mean closed-set test scores 12 months post-implantation were 51.4% and 68.5% for group 1 and group 2, respectively. Schmid-Giovannini test scores were 8.7 for group 1 and 10.1 for group 2. There was no significant statistical difference in the closed-set and Schmid-Giovannini test scores. We observed incomplete insertion (i.e. less than 22 active bands are intracochlear) because of electrode extrusion in only one child. CONCLUSION: Speech development in children does not improve with deeper insertion of the cochlear implant electrode array.

Age Factors↗
PubMed2001

[Hemobahn endoprosthesis: experience with percutaneous placing in the arteria femoralis superficialis].

The self-expanding Polytetrafluoroethylene-lined nitinolstent Hemobahn offers from its design a prophylaxis for re-occlusion after angioplasty of long femoral artery occlusions. During the last two years we placed in 33 patients at 35 extremities a total of 53 Hemobahns. Fontaine's clinical stages were: 30 x IIb, 1 x III and 4 x IV. The treated lesions were femoral stenoses (3x) and occlusions (32x with mean distance 12 cm). Follow-up-visits were after 3, 6 and 12 months. The mean ankle-brachial-index changed from 0.49 to 0.85, post-interventional Fontaine's stages were: 24 x I, 5 x IIa, 2 x IIb and 4 x IV. The primary inhospital patency rate was 91%. After 3 months all primary/secondary patency rates were: 77%/87%, after 6 months 62%/85% and after 1 year 40%/67%. Causes for re-occlusions were a poor "run off", calcifications and multiple vessel lesions. The results for "ideal indications" were much better. Such "ideal indications" applied to: > or = 1 cm "healthy" proximal and distal vascular segments, missing lesions in the popliteal artery, at least one open lower leg vessel and no severe calcifications. The primary/secondary patency rate was inhospital 100% (n = 23), after 3 months 95/100%, after 6 months 85/100% and after 1 year 80/100%. Side effects were local haematoma, pain in the prosthesis and temporarily temperature reactions. Sonographically no re-stenoses at the limb ends were observed. Hemobahn-endoprostheses are suited for therapy of long femoral artery occlusions. The medium patency rate of "ideal indications" is higher than that of angioplasty with or without uncovered stents.

Aged↗