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11.
Katrin Decker Andreas Koschinski Sylvia Trouliaris T. Tamura Florian Dreyer H. Repp 《Naunyn-Schmiedeberg's archives of pharmacology》1998,357(4):378-384
We investigated the effects of the receptor-coupled protein tyrosine kinase (RTK) v-Fms on the membrane current properties
of NIH3T3 mouse fibroblasts. We found that v-Fms, the oncogenic variant of the macrophage colony-stimulating factor receptor
c-Fms, activates a K+ current that is absent in control cells. The activation of the K+ current was Ca2+-dependent, voltage-independent, and was completely blocked by the K+ channel blockers charybdotoxin, margatoxin and iberiotoxin with IC50 values of 3nM, 18 nM and 76nM, respectively. To identify signalling components that mediate the activation of this K+ current, NIH3T3 cells that express different mutants of the wildtype v-Fms receptor were examined. Mutation of the binding
site for the Ras-GTPase-activating protein led to a complete abolishment of the K+ current. A reduction of 76% and 63%, respectively, was observed upon mutation of either of the two binding sites for the
growth factor receptor binding protein 2. Mutation of the ATP binding lobe, which disrupts the protein tyrosine kinase activity
of v-Fms, led to a 55% reduction of the K+ current. Treatment of wild-type v-Fms cells with Clostridium sordellii lethal toxin or a farnesyl protein transferase inhibitor, both known to inhibit the biological function of Ras, reduced the
K+ current amplitude to 17% and 6% of the control value, respectively. This is the first report showing that an oncogenic RTK
can modulate K+ channel activity. Our results indicate that this effect is dependent on the binding of certain Ras-regulating proteins to
the v-Fms receptor and is not abolished by disruption of its intrinsic protein tyrosine kinase activity. Furthermore, our
data suggest that Ras plays a key role for K+ channel activation by the oncogenic RTK v-Fms.
Received: 19 November 1997 / Accepted: 21 January 1998 相似文献
12.
Lamszus K Makrigeorgi-Butera M Laas R Westphal M Stavrou D 《Brain pathology (Zurich, Switzerland)》2003,13(1):115-117
The September 2002 COM. A 24-year-old female presented with a history of 3 generalized seizures, the first of which had occurred 6 months before admission. Her neurological examination was normal, but upon admission her MRI showed a small cystic lesion in the left parieto-occipital region. The lesion was hyper-intense on T-2 weighted images and did not show contrast enhancment. At surgery, the tumor was found to be deep to the cortex and was a cyst with amber fluid surrounded by gliotic brain. Microscopically, the tumor was well-demarcated from the surrounding tissues, which showed reactive changes, including Rosenthal fibers. The tumor was composed of GFAP-positive glial cells, which were arranged in a pseudopapillary fashion around blood vessels. In between, the tumor cells were positive for neuronal markers. The diagnosis was papillary glioneuronal tumor (PGNT), a relatively recently described lesion that may be a variant of ganglioglioma. The current literature on PGNTs is reviewed. 相似文献
13.
Tumor Vascularity Is Not a Prognostic Factor for Malignant Melanoma of the Skin 总被引:1,自引:4,他引:1 下载免费PDF全文
Klaus J. Busam Marianne Berwick Karen Blessing Katrin Fandrey Sewon Kang Themis Karaoli Judy Fine Alistair J. Cochran Wain L. White Jason Rivers David E. Elder Duan-Ren Po Wen Bradley H. Heyman Raymond L. Barnhill 《The American journal of pathology》1995,147(4):1049-1056
Tumor vascularity has been proposed as a prognostic indicator for a number of solid tumors. Although a correlation between microvessel number and metastatic behavior has also been suggested for cutaneous melanoma, the small number of cases studied to date allows one to draw only preliminary conclusions. In this study, we have assessed tumor vascularity in cutaneous melanoma by comparing 60 cases of metastasizing and non-metastasizing tumors matched for tumor thickness, age, sex, and anatomic site. Ulex europaeus agglutinin I appeared to be the most suitable vascular marker for this study. Our results indicate that there was no statistically significant difference between the two groups with regard to tumor vascularity. Even after identifying 15 cases of thin (<1.0 mm thick) melanoma, there was no significant difference in the number of microvessels between metastasizing and non-metastasizing tumors. Comparison of patterns of vascular microarchitecture also failed to discriminate between the two groups. Thus, our results indicate that tumor vascularity may not be an independent prognostic factor for cutaneous melanoma. 相似文献
14.
15.
Kaindl AM Jakubiczka S Lücke T Bartsch O Weis J Stoltenburg-Didinger G Aksu F Oexle K Koehler K Huebner A 《Human mutation》2005,26(3):279-280
Microdeletion syndromes are commonly transmitted as dominant traits and are frequently associated with variably expressed pleiotropic phenotypes. Nonlethal homozygous microdeletions, on the other hand, are very rare. Here, we delineate the fifth and so far largest homozygous microdeletion in nonmalignancies of approximately 400 kb on chromosome 4q11-q12 in a large consanguineous East-Anatolian family with six affected patients. The deleted region contains the beta-sarcoglycan gene (SGCB), the predicted gene SPATA18 (spermatogenesis associated 18 homolog) and several expressed sequence tags. Patients presented with a severe and progressive Duchenne-like muscular dystrophy phenotype, a combination of hyperlaxity and joint contractures, chest pain, palpitations, and dyspnea. 相似文献
16.
TLR4 gene variants modify endotoxin effects on asthma 总被引:6,自引:0,他引:6
Werner M Topp R Wimmer K Richter K Bischof W Wjst M Heinrich J 《The Journal of allergy and clinical immunology》2003,112(2):323-330
BACKGROUND: Environmental exposure to endotoxin might have a crucial role in immune maturation and development of asthma. OBJECTIVE: The aim of this study was to investigate whether the effect of endotoxin concentration in settled house dust on asthma is modified by the presence of variation in the TLR4 gene. METHODS: We performed a cross-sectional study within the German follow-up of the European Community Respiratory Health Survey. Multivariate logistic regression analysis and nonparametric effect estimates (S-Plus) were applied to examine the association between endotoxin exposure and diagnosed asthma, related clinical symptoms, and bronchial hyperreactivity (BHR) stratified for noncarriers and carriers of G299/I399 polymorphism in the TLR4 gene. RESULTS: In the noncarrier group (n = 279), the prevalence of asthma was significantly increased with elevated endotoxin levels in house dust with adjusted odds ratio 6.24 (95% CI, 1.33-29.17) in the second tertile, and 4.54 (95% CI, 0.94-21.96) in the third tertile compared with the lowest endotoxin tertile. The carriers of the polymorphisms (n = 55) showed a nonsignificant trend to have a lower risk of asthma (crude odds ratio, 0.67; 95% CI, 0.06-8.06 for the second tertile and 1.33; 95% CI, 0.17-10.58 for the third tertile). We found a similar association for wheeze and endotoxin exposure that was also attenuated in subjects with G299/I399 polymorphisms. CONCLUSIONS: The G299/I399 polymorphisms were associated with a modified response to endotoxin, but the functional relationship still needs clarification. 相似文献
17.
Temperature-mediated heteroduplex analysis for detection of pncA mutations associated with pyrazinamide resistance and differentiation between Mycobacterium tuberculosis and Mycobacterium bovis by denaturing high- performance liquid chromatography 下载免费PDF全文
Mohamed AM Bastola DR Morlock GP Cooksey RC Hinrichs SH 《Journal of clinical microbiology》2004,42(3):1016-1023
The goal of this study was to apply temperature-mediated heteroduplex analysis using denaturing high-performance liquid chromatography to identify pyrazinamide (PZA) resistance in Mycobacterium tuberculosis isolates and simultaneously differentiate between M. tuberculosis and Mycobacterium bovis. Features that contributed to an optimal assay included the use of two different reference probes for the pncA gene targets from wild-type M. tuberculosis and wild-type M. bovis, optimization of the column temperature, increasing the starting concentration of the elution buffer, and reducing the rate of elution buffer increase (slope). A total of 69 strains were studied, including 48 wild-type M. tuberculosis strains (13 were PZA-resistant strains) and 21 M. bovis strains (8 were BCG strains). In all isolates tested, wild-type M. tuberculosis generated a single-peak pattern when mixed with the M. tuberculosis probe and a double-peak pattern with the M. bovis probe. In contrast, all M. bovis isolates generated a double-peak pattern when mixed with the M. tuberculosis probe and a single-peak pattern with the M. bovis probe. PZA-resistant mutant M. tuberculosis isolates generated characteristic patterns that were easily distinguishable from both wild-type M. tuberculosis and M. bovis isolates. Chromatographic patterns generated by the two reference probes allowed the rapid detection of PZA resistance with the simultaneous ability to distinguish between M. tuberculosis and M. bovis. This approach may allow the detection of drug resistance-associated mutations, with potential application to clinical and epidemiological aspects of tuberculosis control. 相似文献
18.
Morphological detection and quantification of lipoprotein(a) deposition in atheromatous lesions of human aorta and coronary arteries 总被引:8,自引:0,他引:8
Axel Niendorf Matthias Rath Katrin Wolf Susanne Peters Hartmut Arps Ulrike Beisiegel Manfred Dietel 《Virchows Archiv : an international journal of pathology》1990,417(2):105-111
Summary Lipoprotein(a), as an atherogenic particle, represents an independent risk factor for coronary heart disease. In the present
study the morphological distribution of apoprotein (a) and apoprotein B within the arterial wall is described. Apoprotein
B, a constituent of very low-density lipoprotein, low-density lipoprotein and lipoprotein(a) has previously been demonstrated
in atheromatous lesions. Lipoprotein(a) possesses an additional protein, designated apoprotein (a). Autopsy material (n=74) from the left coronary artery and from the thoracic aorta has been examined by means of immunohistochemistry and both
apoprotein (a) and apoprotein B were detected, primarily associated with the extracellular matrix and accumulating in lesions
in the arterial wall. The staining pattern for both antigens was almost always found to be congruent, suggesting that the
detection of (a)-antigen has to be attributed at least in part to the presence of lipoprotein(a). It is concluded that both
low-density lipoprotein and lipoprotein(a) have an important role in the pathogenesis of atherosclerosis. 相似文献
19.
Identification of Aspergillus species using internal transcribed spacer regions 1 and 2 总被引:15,自引:0,他引:15
Aspergillus species are the most frequent cause of invasive mold infections in immunocompromised patients. Although over 180 species are found within the genus, 3 species, Aspergillus flavus, A. fumigatus, and A. terreus, account for most cases of invasive aspergillosis (IA), with A. nidulans, A. niger, and A. ustus being rare causes of IA. The ability to distinguish between the various clinically relevant Aspergillus species may have diagnostic value, as certain species are associated with higher mortality and increased virulence and vary in their resistance to antifungal therapy. A method to identify Aspergillus at the species level and differentiate it from other true pathogenic and opportunistic molds was developed using the 18S and 28S rRNA genes for primer binding sites. The contiguous internal transcribed spacer (ITS) region, ITS 1-5.8S-ITS 2, from referenced strains and clinical isolates of aspergilli and other fungi were amplified, sequenced, and compared with non-reference strain sequences in GenBank. ITS amplicons from Aspergillus species ranged in size from 565 to 613 bp. Comparison of reference strains and GenBank sequences demonstrated that both ITS 1 and ITS 2 regions were needed for accurate identification of Aspergillus at the species level. Intraspecies variation among clinical isolates and reference strains was minimal. Sixteen other pathogenic molds demonstrated less than 89% similarity with Aspergillus ITS 1 and 2 sequences. A blind study of 11 clinical isolates was performed, and each was correctly identified. Clinical application of this approach may allow for earlier diagnosis and selection of effective antifungal agents for patients with IA. 相似文献
20.
Katrin Banach Moritz Bünemann Jörg Hüser Lutz Pott 《Pflügers Archiv : European journal of physiology》1993,423(3-4):245-250
L-type Ca2+ current (I
Ca) was measured in cultured atrial myocytes from hearts of adult guinea-pigs using whole-cell voltage clamp. Potentiation of I
Ca induced by -adrenergic stimulation (isoprenaline 2· 10–7 M) could be completely antagonized by diluted sera (1100 v/v). Half-maximal inhibition of -receptorstimulated I
Ca occurred at about 11000. Basal I
Ca was not affected by serum. Atropine in a concentration (10–6M) that completely antagonized the anti-adrenergic effect of acetylcholine (ACh, 2·10–6 M) did not interfere with the effect of serum. In cells dialysed with cyclic adenosine monophosphate (cAMP)-containing (10–4 M) pipette solution, potentiated I
Ca was insensitive to both ACh and serum. Preincubation of the myocytes with pertussis toxin almost completely abolished the anti-adrenergic effects of both ACh and serum. The potency of serum was not reduced by dialysis. It is concluded that serum contains a factor which, like ACh, inhibits -receptor-stimulated adenylyl cyclase via Giprotein.A preliminary report of this work has appeared in abstract form [11] 相似文献