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51.
Mechanisms of cold sensitivity of paramyotonia congenita mutation R1448H and overlap syndrome mutation M1360V 总被引:1,自引:2,他引:1
Bahram Mohammadi Nenad Mitrovic Frank Lehmann-Horn Reinhard Dengler Johannes Bufler 《The Journal of physiology》2003,547(3):691-698
Missense mutations of the human skeletal muscle voltage-gated Na+ channel (hSkM1) cause a variety of neuromuscular disorders. The mutation R1448H results in paramyotonia congenita and causes cold-induced myotonia with subsequent paralysis. The mutation M1360V causes an overlapping syndrome with both K+ -induced muscle weakness and cold-induced myotonia. The molecular mechanisms of the temperature dependence of these disorders are not well understood. Therefore we investigated physiological parameters of these Na+ channel mutations at different temperatures. Channel proteins were recombinantly expressed in human embryonic kidney cells and studied electrophysiologically, using the whole-cell patch-clamp technique. We compared the wild-type (WT) channel with both mutants at different temperatures. Both mutations had slower inactivation and faster recovery from inactivation compared to WT channels. This effect was more pronounced at the R1448H mutation, leading to a larger depolarization of the cell membrane causing myotonia and paralysis. The voltage dependence of activation of R1448H was shifted to more negative membrane potentials at lower temperature but not at the M1360V mutation or in the WT. The window current by mutation R1448H was increased at lower temperatures. The results of this study may explain the stronger cold-induced clinical symptoms resulting from the R1448H mutation in contrast to the M1360V mutation. 相似文献
52.
Wellinghausen N Sing A Kern WV Perner S Marre R Rentschler J 《International journal of medical microbiology : IJMM》2002,292(1):59-63
A 77-year-old farmer developed cough with sputum production, fever, bloody nasal discharge and a mass in his right maxillary sinus leading to necrotic ulceration of the sinus. Corynebacterium ulcerans, carrying the beta-phage for the diphtheria toxin and secreting the toxin, was detected microscopically and by culture from the sinusoidal and ulcer discharge. Despite immediate antimicrobial chemotherapy the patient died of pulmonary failure associated with the production of large amounts of very viscous sputum. Identification of the causative agent, pathophysiological aspects and risk factors of this unusal infection are discussed. 相似文献
53.
Robinson PN Booms P Katzke S Ladewig M Neumann L Palz M Pregla R Tiecke F Rosenberg T 《Human mutation》2002,20(3):153-161
The Marfan syndrome (MFS) is a pleiotropic, autosomal dominant disorder of connective tissue with highly variable clinical manifestations including aortic dilatation and dissection, ectopia lentis, and a series of skeletal anomalies. Mutations in the gene for fibrillin-1 (FBN1) cause MFS, and at least 337 mainly unique mutations have been published to date. FBN1 mutations have been found not only in MFS but also in a range of connective tissue disorders collectively termed fibrillinopathies ranging from mild phenotypes, such as isolated ectopia lentis, to severe disorders including neonatal MFS, which generally leads to death within the first two years of life. The present article intends to provide an overview of mutations found in MFS and related disorders and to discuss potential genotype-phenotype correlations in MFS. 相似文献
54.
Hubert Sch?fer Katrin Klippert Petra Meuer Bettina Borsdorf Albrecht F Kiderlen Reinhard Burger 《Journal of interferon & cytokine research》2007,27(4):305-315
Interferon-gamma (IFN-gamma) plays a key role in the induction and maintenance of immunity against intracellular infectious agents. Compared to other species, little is known about the biology of this cytokine in the guinea pig (Cavia porcellus). We found that in contrast to humans and mice, IFN-gamma in the guinea pig did not induce the antiviral state, which in other species leads to protection of IFN-gamma -stimulated fibroblasts from the cytopathic effect (CPE) of subsequent viral infections. As an alternative strategy to detect and quantify guinea pig IFN-gamma activity in vitro, a reporter system using guinea pig fibroblasts transfected with a luciferase gene, which is regulated by an IFN-stimulated response element (ISRE), was established. With the help of the highly sensitive reporter assay system, the biologic activity of recombinant guinea pig IFN-gamma (GpIFN-gamma, from prokaryotic and eukaryotic expression systems was detected. The response to both native and recombinant GpIFN-gamma was inhibited by a rabbit antiserum directed against the recombinant cytokine expressed in Escherichia coli, demonstrating structural and functional homology of native and recombinant GpIFN-gamma. Stimulation with GpIFN-gamma, obtained from transfected cells, induced upregulation of MHC class I expression in a guinea pig fibroblast line. The restricted activity of GpIFN-gamma might have implications for this species' ability to control infections with intracellular pathogens. 相似文献
55.
Bell C Vanderlinden H Hiersemenzel R Otoul C Nutt D Wilson S 《Journal of sleep research》2002,11(3):255-263
Levetiracetam is a novel antiepileptic drug which has recently been released as an adjunctive treatment for partial epilepsy. In the two studies reported here we examined the objective and subjective effects of levetiracetam on sleep in 12 healthy volunteers and 17 patients [16 who could be evaluated for electroencephalogram (EEG) recordings] with a history of partial epilepsy on stable carbamazepine monotherapy. The studies were of a similar double-blind crossover placebo-controlled design with subjects' sleep being recorded in their own homes. The results from the two studies showed considerable similarities. In both, levetiracetam produced an increase in the time spent in stage 2 sleep, which in the patient study was accompanied by a decrease in the time spent in stage 4 sleep and in the volunteer study an increase in rapid eye movement (REM) latency. The subjective changes included reports that sleep was of a better quality with fewer awakenings and patients also reported that their sleep was more restful. Volunteers and patients did, however, feel less alert on waking in the morning. Therefore, both groups reported a decrease in awakenings after levetiracetam despite the finding from the EEG of no change in the actual number of awakenings. It may be concluded from both studies that levetiracetam does affect some indicators of subjective sleep perception, but does not influence objective sleep measures of sleep continuity. The results from the patient study during placebo add-on treatment also showed that patients on carbamazepine had a marked increase in SWS, an increase in stage 2 sleep and an increase in REM latency compared with healthy volunteers. Interestingly, levetiracetam also reduced bilateral epileptiform EEG activity, particularly in patients with more discharges. 相似文献
56.
Zheng B Cao KY Chan CP Choi JW Leung W Leung M Duan ZH Gao Y Wang M Di B Hollidt JM Bergmann A Lehmann M Renneberg I Tam JS Chan PK Cautherley GW Fuchs D Renneberg R 《Clinical immunology (Orlando, Fla.)》2005,116(1):18-26
Neopterin and C-reactive protein (CRP) concentrations were determined in serum samples from 129 severe acute respiratory syndrome (SARS) patients and 156 healthy blood donors. In the patients with confirmed SARS, an early neopterin elevation was detected already at the day of onset of symptoms and rose to a maximum level of 45.0 nmol/L 3 days after the onset. All SARS patients had elevated neopterin concentrations (>10 nmol/L) within 9 days after the onset. The mean neopterin concentrations were 34.2 nmol/L in acute sera of SARS patients, 5.1 nmol/L in convalescent sera, and 6.7 nmol/L in healthy controls. In contrast, the mean CRP concentrations in both acute and convalescent sera of SARS patients were in the normal range (<10 mg/L). Serum neopterin level in SARS patients was associated with fever period and thus the clinical progression of the disease, while there was no significant correlation between the CRP level and the fever period. Serum neopterin may allow early assessment of the severity of SARS. The decrease of neopterin level was found after steroid treatment, which indicates that blood samples should be collected before steroid treatment for the neopterin measurement. 相似文献
57.
Lazar A Gründemann D Berkels R Taubert D Zimmermann T Schömig E 《Journal of human genetics》2003,48(5):226-230
The extraneuronal monoamine transporter EMT (HGNC Nomenclature SLC22A3) is the molecular correlate of the classical uptake2 system responsible for the non-neuronal inactivation of circulating and centrally released catecholamines. Because of its
functional profile and expression pattern, EMT is regarded as a candidate gene for diseases related to the sympathetic nervous
system and neuropsychiatric disorders. We describe the first investigation of the genetic variability of the EMT gene in human.
Six single-nucleotide substitutions and one deletion were detected within the assumed core promoter, the exonic and flanking
intronic sequences and the 3'-untranslated region in 100 Caucasian individuals. No amino acid changes were found and Tajima's
D was positive (D=2.91; P<0.01). However, the synonymous nucleotide substitution 1233G→A might serve as a cryptic splice acceptor site. Analysis of
linkage disequilibrium between polymorphisms yielded 12 possible haplotypes accounting for more than 90% of all haplotypes.
Knowledge of the sequence variation and frequency of the underlying polymorphisms in this member of the amphiphilic solute
facilitator family of transporters provides the basis for subsequent association studies and candidate gene approaches.
Electronic Publication 相似文献
58.
Matthias Wicklmayr Günther Dietze Bernulf Günther Richard Schifmann Ingolf Böttger Reinhard Geiger Hans Fritz Hellmut Mehnert 《Inflammation research》1980,10(4):339-343
The influence of synthetic bradykinin (BK) on disturbed protein and carbohydrate metabolism was studied in chemical and manifest maturity-onset diabetics, in surgical patients and in alloxan diabetic rats. BK,mixed with insulin and injected subcutaneously twice daily in alloxan diabetic rats lowered the morning blood glucose concentration in a dose-dependent way, whereas in a control group treated with insulin only no decrease was seen. Accelerated local blood flow or enhanced vascular permeability as a cause of increased glucose uptake could be ruled out by control experiments using papaverine and eledoisin. Better metabolic control in the BK/insulin-treated group was also indicated by lower arterial levels of free fatty acids and of -hydroxybutyrate, normalized hepatic glycogen content and better growth of body weight. In healthy man an intravenous infusion of BK (80 g/h) did not influence normal fasting blood glucose concentrations, whereas elevated glucose levels in maturity-onset diabetics were continuously reduced within 100 min by 12.2±1.4%. A comparable diabetic group receiving saline alone showed no spontaneous drop of blood glucose concentration. An improvement of pathological carbohydrate metabolism by infusion of BK i.v. could also be demonstrated using the intravenous glucose tolerance test in chemical and manifest maturity-onset diabetics and in surgical patients: in all groupsk values of the glucose tolerance test were significantly increased by BK. This effect was neither due to stimulated insulin release nor to changed glucose pool or to increased renal glucose loss, which was even reduced by BK. Interestingly, normalk values in healthy volunteers were not further improved by BK. A stimulated protein breakdown, which occurs after surgery due to peripheral insulin resistance, can also be restricted by intravenous infusion of BK: in surgical patients urinary nitrogen excretion was reduced by 50% during infusion of BK and was accelerated again after cessation of the infusion. These results indicate that BK can improve the efficacy of exogenous insulin in insulin-deficient animals and depressed insulin sensitivity in maturity-onset diabetics and surgical patients. 相似文献
59.
Active detachment involves inhibition of cell-matrix contacts of malignant melanoma cells by secretion of melanoma inhibitory activity 总被引:3,自引:0,他引:3
Bosserhoff AK Stoll R Sleeman JP Bataille F Buettner R Holak TA 《Laboratory investigation; a journal of technical methods and pathology》2003,83(11):1583-1594
Melanoma inhibitory activity (MIA) has been identified as a small protein secreted from malignant melanoma cells. Recent results revealed a direct interaction of MIA and epitopes within extracellular matrix proteins including fibronectin. The aim of this study was to analyze functional consequences mediated by this interaction. Here we show that MIA interferes specifically with attachment of melanoma cells to fibronectin, a phenomenon we refer to as active detachment. Antibodies inhibiting binding of alpha4beta1 and alpha5beta1 integrins to fibronectin cross-react specifically with MIA, suggesting that MIA shares significant structural homology with the binding pockets of these integrins and thereby masks the respective epitopes on extracellular matrix molecules. Several peptides derived from fibronectin and from a phage display screening were tested with respect to a potential MIA-inhibitory effect. In vitro tests identified two peptides affecting MIA function; both inhibited growth of melanoma metastases in vivo. In summary, we conclude that MIA may play a role in tumor progression and spread of malignant melanomas via mediating active detachment of cells from extracellular matrix molecules within their local milieu. Further, our results suggest that inhibiting MIA functions in vivo may provide a novel therapeutic strategy for metastatic melanoma disease. 相似文献
60.
S. Breitner-Ruddock Reinhard Würzner Jörg Schulze V. Brade 《Medical microbiology and immunology》1997,185(4):253-260
Sixteen Borrelia burgdorferi strains, including all three species, were compared in a colorimetric bactericidal assay for their ability to escape the
complement-dependent bacteriolysis on incubation in normal human serum free of specific antibodies (NHS). The species B. afzelii was found to be serum resistant (EB1, EB3, FEM1, FEM2, Pko), whereas strains of the species B. garinii were found to be serum sensitive (1/B29, G1, G2, PSth, PBr, PTrob). Six strains, mainly B. burgdorferi sensu stricto, were only partially sensitive (Z25, 297, B31, PKa-I, PBi). All strains activated the complement cascade in NHS, whereas only
four strains (G1, G2, PBr, PSth) could activate complement in the presence of EGTA-Mg. After complement activation, covalently
bound C3 fragments (C3b, iC3b) were detected on serum-sensitive as well as serum-resistant borrelial strains. Heterogeneity,
however, was observed between serum-resistant and serum-sensitive strains with respect to deposition of C6 and C9. Whereas
serum-sensitive strains were strongly positive for C6 and C9 and were, therefore, killed by the terminal complement complex
(TCC), serum-resistant strains were devoid of C6 and C9 on their cell surface. The serum resistance may, therefore, be due
to an absent or only transient formation of TCC on the bacterial surface.
Received: 17 September 1996 相似文献