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11.
The GAP-related domain of tuberin, the product of the TSC2 gene, is a target for missense mutations in tuberous sclerosis 总被引:5,自引:0,他引:5
Maheshwar MM; Cheadle JP; Jones AC; Myring J; Fryer AE; Harris PC; Sampson JR 《Human molecular genetics》1997,6(11):1991-1996
Tuberous sclerosis is an autosomal dominant trait in which the
dysregulation of cellular proliferation and differentiation results in the
development of hamartomatous growths in many organs. The TSC2 gene is one
of two genes determining tuberous sclerosis. Inactivating germline
mutations of TSC2 in patients with tuberous sclerosis and somatic loss of
heterozygosity at the TSC2 locus in the associated hamartomas indicate that
TSC2 functions as a tumour suppressor gene and that loss of function is
critical to expression of the tuberous sclerosis phenotype. The TSC2
product, tuberin, has a region of homology with the GTPase activating
protein rap1GAP and stimulates the GTPase activity of rap1a and rab5a in
vitro. Here we show that the region of homology between tuberin and human
rap1GAP and the murine GAP mSpa1 is more extensive than previously reported
and spans approximately 160 amino acid residues encoded within exons 34-38
of the TSC2 gene. Single strand conformation polymorphism analysis of these
exons in 173 unrelated patients with tuberous sclerosis and direct
sequencing of variant conformers together with study of additional family
members enabled characterisation of disease associated mutations in 14
cases. Missense mutations, which occurred in exons 36, 37 and 38 were
identified in eight cases, four of whom shared the same recurrent change
P1675L. Each of the five different missense mutations identified was shown
to occur de novo in at least one sporadic case of tuberous sclerosis. The
high proportion of missense mutations detected in the region of the TSC2
gene encoding the GAP-related domain supports its key role in the
regulation of cellular growth.
相似文献
12.
Mahadevan MM; McIntosh Q; Miller MM; Breckinridge SM; Maris M; Moutos DM 《Human reproduction (Oxford, England)》1998,13(4):979-982
Cryopreservation of human zygotes and embryos has been routinely performed
by in-vitro fertilization clinics for many years. Karran and Legge (1996)
first reported that formaldehyde (FA) present in the cryoprotective
solutions can have a deleterious effect on mouse oocytes. FA is a
cytotoxic, carcinogenic and mutagenic chemical. The effect of FA on mouse
zygotes was investigated. In addition, the concentrations of FA in
propanediol (PROH) obtained from various sources were determined. Pooled
1-cell embryos were dispensed into droplets of modified Ham's F10 or human
tubal fluid containing various concentrations of FA. Since bovine serum
albumin (BSA) may minimize toxicity additional trials were done as above in
the absence of BSA. FA concentration in the standard 1.5 M PROH, from
different sources in water, was measured in the same assay using a standard
curve of 0-100 microM FA. FA in a complex medium had a significant
deleterious effect on embryo development and hatching but only at 1 mM
concentration (P < 0.000001; see Tables I-III). There was no significant
effect of FA at 100 microM. However, in a simple medium even 50 microM FA
decreased embryo hatching. FA was present in 1.5 M PROH from different
sources (range 1.0-35.3 microM concentration). It appears that FA
concentrations do not increase with storage because FA concentrations were
low even after opening and storage for 3 years on the shelf. This suggests
that FA is a contaminant during the manufacturing process and may vary from
manufacturer to manufacturer and batch to batch. Until further studies are
done to confirm the lack of toxicity to embryos during cryopreservation
(with or without FA scavengers) it may be prudent to screen all batches of
cryoprotectants for FA as part of quality control.
相似文献
13.
Renal gluconeogenesis and increased glucose utilization in shock 总被引:1,自引:0,他引:1
14.
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16.
The meta-analysis was performed to assess the efficacy and safety of daily oral L-arginine and phosphodiesterase type 5 inhibitors (PDE5Is) alone or combination in treating patients with erectile dysfunction (ED). We performed a search of randomised controlled trials in the following databases: PubMed, EMBASE and Cochrane Library databases. Four articles including 373 patients were studied. Erectile functions were significantly improved in three therapy groups compared with baseline. Patients who received the combination of L-arginine and PDE5Is showed significant improvement compared to those treated with L-arginine and PDE5Is alone, as assessed by sexual function index (p <0.00001 and p =0.005, respectively) and total testosterone (p <0.00001 and p =0.0007, respectively). Furthermore, patients who treated with PDE5Is alone exhibited the better efficacy than those treated with L-arginine alone in respects of sexual function index (p <0.00001) and total testosterone (p =0.0001). However, the combination of L-arginine and PDE5Is had no obvious difference relative to PDE5Is alone in terms of various adverse events (AEs). Conclusively, compared with monotherapy, the combination of L-arginine and PDE5Is showed a greater improvement of sexual function and total testosterone, and did not significantly increase the AEs. Besides, PDE5Is alone revealed a better effect than those treated with L-arginine alone for patients with ED. 相似文献
17.
Jue Chen MD PhD Lei Guo MM Lian Gu MPsy Hui Han MPsy 《The International journal of eating disorders》2021,54(1):102-106
In the past 40 years, the prevalence of eating disorders (ED) in China has shown an increasing trend, leading to an urgent need to develop efficient treatment modes and methods. Since the beginning of the new century, the diagnosis, treatment, and research of ED in China have been under development. This article gives an introduction and commentary on the treatment modes, treatment methods and their applications in ED in China. There are two main treatment forms for ED until now, that is, inpatient treatment and outpatient treatment. Inpatient treatment is recommended as the first choice. Since 2008, clinical psychotherapies such as cognitive behavioral therapy (CBT), dialectical behavioral therapy (DBT), and family-based treatment (FBT), which are effective for pathological symptoms of ED, have been introduced into China and developed clinically. Group CBT and group DBT for patients with ED and group FBT for caregivers might be the most efficient psychotherapy in China nowadays. A multi-family FBT support group could be developed as the basic treatment of ED patients. Although these new types of psychotherapy have observed effectiveness in clinical application, the Randomized Controlled Trials (RCT) are rare and need to be developed. 相似文献
18.
19.
M-Yasmine Bottein Dechraoui Zhihong Wang Jean Turquet Mireille Chinain Taiana Darius Philippe Cruchet Faisal F Y Radwan Robert W Dickey John S Ramsdell 《Toxicon》2005,46(3):243-251
Ciguatera is a human food poisoning caused by consumption of tropical and subtropical fish that have, through their diet, accumulated ciguatoxins in their tissues. This study used laboratory mice to investigate the potential to apply blood collection cards to biomonitor ciguatoxin exposure. Quantitation by the neuroblastoma cytotoxicity assay of Caribbean ciguatoxin (C-CTX-1) spiked into mice blood was made with good precision and recovery. The blood collected from mice exposed to a sublethal dose of Caribbean ciguatoxic extract (0.59 ng/g C-CTX-1 equivalents) was analyzed and found to contain detectable toxin levels at least 12 h post-exposure. Calculated concentration varied from 0.25 ng/ml at 30 min post-exposure to 0.12 ng/ml at 12 h. A dose response mice exposure revealed a linear dose-dependent increase of ciguatoxin activity in mice blood, with more polar ciguatoxin congeners contributing to 89% of the total toxicity. Finally, the toxin measurement in mice blood exposed to toxic extracts from the Indian Ocean or from the Pacific Ocean showed that the blood collection card method could be extended to each of the three known ciguatoxin families (C-CTX, I-CTX and P-CTX). The low matrix effect of extracted dried-blood samples (used at 1:10 or 1:20 dilution) and the high sensitivity of the neuroblastoma assay (limit of detection 0.006 ng/ml C-CTX-1), determined that the blood collection card method is suitable to monitor ciguatoxin at sublethal doses in mice and opens the potential to be a useful procedure for fish screening, environmental risk assessment or clinical diagnosis of ciguatera fish poisoning in humans or marine mammals. 相似文献
20.
应用改进的眼震图检查先天性眼球震颤 总被引:2,自引:0,他引:2
目的评价改进后的眼震图对先天性眼球震颤波形的分析,为其手术治疗提供较为精确的量化标准.方法改进电生理仪的视网膜电图(EOG)程序,分别记录68例患者33cm原在位、右5°、10°、15°、20°,左5°、10°、15°、20°,3m原在位及闭眼的波形,并对其中28例手术患者术前和术后的眼震图进行比较.结果68例患者中,跳动型48例,其中水平跳动46例,垂直跳动2例;水平钟摆型20例.跳动型中,有代偿头位的40例,钟摆型无明显代偿头位.28例手术患者中,水平跳动型26例,水平钟摆型2例.26例跳动型患者均有中间位和代偿头位.术后20例代偿头位消失,6例代偿头位在左5°~10°.按震频、振幅、震强的分组中,处于中等震频、振幅、震强范围内的多见.结论改进的眼震图可以对眼震的振幅、震频、震强、中间位进行量化的检测,从而指导其治疗. 相似文献