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991.
Multiple novel alterations in Kit tyrosine kinase in patients with gastrointestinally pronounced systemic mast cell activation disorder 总被引:1,自引:0,他引:1
Molderings GJ Kolck UW Scheurlen C Brüss M Homann J Von Kügelgen I 《Scandinavian journal of gastroenterology》2007,42(9):1045-1053
OBJECTIVE: Sequencing efforts to discover mutations in the tyrosine kinase Kit related to systemic mast cell disorders have so far been focused mainly on only a few of the 21 exons of the encoding gene c-kit, thus considerably limiting the possibility to quantitatively reveal pathogenetic relationships. The purpose of this study was to analyze and compare the total sequence of Kit tyrosine kinase at the level of the mRNAs obtained from patients with clear systemic signs of a pathologically increased mast cell mediator release and those from healthy volunteers. MATERIAL AND METHODS: Kit encoding mRNA isolated from mast cell progenitors in peripheral blood from 17 patients with a mast cell activation disorder and from 5 healthy volunteers as well as from the human mast cell leukemia cell line HMC1 was analyzed for alterations. RESULTS: Multiple novel point mutations and six isoforms of Kit which are due to alternative mRNA splicing were detected. One isoform, the insertion of a glutamine residue at amino acid position 252, was found to be a new splice variant expressed in all patients but in none of the healthy volunteers. CONCLUSIONS: Systemic mast cell activation disorder was pathogenetically characterized by two or more alterations in the Kit tyrosine kinase providing not only a means of confirming the diagnosis, but also of assessing prognosis and of starting adequate therapeutic interventions. The insertion of Q252 appears to be pathognomic for that disease, providing a novel means for the identification of chronic non-specific gastrointestinal symptoms as manifestations of a systemic mast cell activation disorder. 相似文献
992.
In T cell-mediated autoimmune diseases such as rheumatoid arthritis, Th1 cells and their cytokines, especially interferon-gamma (IFN-gamma), are responsible for the induction and persistence of chronic inflammation and tissue destruction. But emerging evidence from experimental models has demonstrated that IFN-gamma also possesses unexpected anti inflammatory properties. The recent data discussed in this article indicate that beside the well-known proinflammatory efficacy, IFN-gamma may function as a master regulator of inflammation and immune responses. Such self-regulatory processes seem to play an important role in the inhibition of excessive responses and to maintain or reestablish homeostasis of the immune system. 相似文献
993.
Grundberg E Akesson K Kindmark A Gerdhem P Holmberg A Mellström D Ljunggren O Orwoll E Mallmin H Ohlsson C Brändström H 《The Journal of clinical endocrinology and metabolism》2007,92(6):2300-2306
CONTEXT: Estrogens regulate bone mass by binding to the estrogen receptor (ER)-alpha as well as ER-beta. The specific ERalpha cofactor retinoblastoma-interacting zinc finger protein (RIZ)-1 enhances ERalpha function in the presence of estrogen. OBJECTIVE: The objective of the study was to determine whether a RIZ P704 insertion (+)/deletion (-) (indel) polymorphism modulates the impact of estradiol on bone mineral density (BMD) and study the association between the polymorphism and BMD in elderly subjects. DESIGN: This was a population-based, prospective, and cross-sectional study, the Swedish MrOS Study, and the Malm? OPRA Study, respectively. SETTING: The study was conducted at three academic medical centers: Sahlgrenska Academy in Gothenburg, Malm? University Hospital, and Uppsala University Hospital. PARTICIPANTS: In total, 4058 men and women, aged 69-81 yr, were randomly selected from population registries. MAIN OUTCOME MEASURES: BMD (grams per square centimeter) was measured at femoral neck, trochanter, lumbar spine, and total body. RESULTS: The RIZ P704(+/+) genotype was associated with low BMD in both women (femoral neck, P < 0.001; trochanter, P < 0.01; lumbar spine, P < 0.05; total body, P < 0.01) and men (lumbar spine, P < 0.05). However, the association between the polymorphism and BMD was dependent on estradiol status. The positive correlation between serum estradiol and BMD was significantly modulated by the genotype with a stronger correlation in the P704(+/+) group than the P704(-/-) group (r = 0.19 vs. r = 0.08, P < 0.05). CONCLUSIONS: These large-scale studies of elderly men and women indicate that the ERalpha cofactor RIZ gene has a prominent effect on BMD, and the P704 genotype modulates the impact of estradiol on BMD. Further studies are required to determine whether this polymorphism modulates the estrogenic response to estradiol treatment. 相似文献
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Brígido LF Nunes CC Oliveira CM Knoll RK Ferreira JL Freitas CA Alves MA Dias C Rodrigues R;Research Capacity Program 《AIDS research and human retroviruses》2007,23(12):1579-1586
HIV-1 B is predominant in Brazil, but HIV-1 C has increasingly been reported in the south of the country. However, many samples clustering with clade C are actually a recombinant, with a small B segment at RT (CRF31). Samples (209) from the three cities with the highest aids prevalence rate are analyzed. Partial polymerase sequences from HIV RNA made it possible to determine HIV clades and recombination patterns and to identify primary drug resistance mutations (DRMs). The incidence was estimated with a BED assay. HIV-1 C and CRF31 patterns were twice as frequent as clade B at all sites, but the proportion of C and CRF31 patterns was significantly different among sites. The incidence estimate for SC was 2.6 persons-years. Infection in recent or younger cases showed no association with clade C. Surveillance DRM was observed in 8.3% (95% CI 5-13), mostly to NNRTIs. Clade F pol genomes had significantly more primary DRM. 相似文献
998.
McBride D Brüggenjürgen B Roll S Willich SN 《Journal of thrombosis and thrombolysis》2007,24(1):65-72
Background Atrial fibrillation (AF) is the most common heart arrhythmia, affecting 6% of people over 65 years, and carries a 4.5% average
annual stroke risk, which can be reduced by appropriate anticoagulation. A multi-centre observational study, Management and Outcomes in the Care of Atrial fibrillation in Germany (MOCA) was conducted to evaluate the current anticoagulation treatment pattern in patients with AF in Germany.
Methods Patients with AF were recruited from December 2003 to June 2004 in physician practices. Clinical data including International
Normalised Ratio (INR) values and anticoagulation strategy were obtained from the physician chart and the patient follow-up,
documenting hospitalisations, medications, and complications, was conducted at three and six months. Main outcome measures
included anticoagulation methods, practice guidelines adherence and time within recommended anticoagulation range.
Results 361 patients with AF (mean age 71±9, 61% male) were recruited in 45 physician practices. 90% of all patients had been treated
with Vitamin K-Antagonists (VKA) at some time since AF-diagnosis, 88% were still treated. 10% of patients received aspirin
as their anticoagulation therapy. Monitoring occurred at least once a month in over 70% of patients. Monitored INR values
were 56% of the time within, 14% below and 30% over the recommended target range. A gap of 40% existed between the guideline
recommendations and actual practice. Younger patients (<60 years of age) with no documented risk factors for stroke were over-treated
with VKAs and patients older than 75 years without contraindications for anticoagulation were under-treated.
Conclusions This study presents ‘real-life’ data in treating patients with AF in Germany and identifies the potential to advance the quality
of care with respect to anticoagulation. 相似文献
999.
Lindquist S Bodammer N Kaufmann J König F Heinze HJ Brück W Sailer M 《Multiple sclerosis (Houndmills, Basingstoke, England)》2007,13(4):471-482
Defining tools in magnetic resonance imaging (MRI) representing specific pathological processes is needed to understand the complex relationship between inflammation, myelin breakdown, axonal injury and clinical symptoms in multiple sclerosis (MS) and its variants. Here, we describe a case of histologically-defined MS, in which the radiological appearance of the lesion and clinical course support the diagnosis of Balo's concentric sclerosis. Serial magnetization transfer, diffusion tensor imaging and 1H-magnetic resonance spectroscopy, from 14 days to 13 months after biopsy, allow the contextual interpretation of specific pathological changes. In our case, acute inflammation was sensitively traced by fractional anisotropy and increased lactate in spectroscopy. In contrast, magnetization transfer ratio and the apparent diffusion coefficient monitor the sequential loss of tissue in selected rings of the lesion. The delay from the peak of symptoms in a dramatic clinical course to the maximum tissue destruction indicated through MRI suggests that compromise of axonal function may be decisive for the acute clinical situation. This is the first report comparing 1H-magnetic resonance spectroscopy, magnetization transfer and diffusion tensor imaging with histopathology in a patient with Balo's concentric sclerosis. 相似文献
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