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41.
Five haplotypes account for fifty-five percent of ATM mutations in Brazilian patients with ataxia telangiectasia: seven new mutations 总被引:7,自引:0,他引:7
Coutinho G Mitui M Campbell C Costa Carvalho BT Nahas S Sun X Huo Y Lai CH Thorstenson Y Tanouye R Raskin S Kim CA Llerena J Gatti RA 《American journal of medical genetics. Part A》2004,(1):33-40
We have studied the molecular genetics of 27 Brazilian families with ataxia telangiectasia (AT). Five founder effect haplotypes accounted for 55.5% of the families. AT is an autosomal recessive disorder of childhood onset characterized by progressive cerebellar ataxia, ocular apraxia, telangiectasia, immunodeficiency, radiation sensitivity, chromosomal instability, and predisposition to cancer. The ATM gene spans more than 150 kb on chromosome region 11q23.1 and encodes a product of 3056 amino acids. The ATM protein is a member of the phosphatidylinositol 3-kinase (PI-3K) family of proteins and is involved in cell cycle control and DNA repair pathways. DNA was isolated from lymphoblastoid cell lines and haplotyped using four STR markers (D11S1818, NS22, D11S2179, D11S1819) within and flanking the ATM gene; all allele sizes were standardized in advance. In addition to the STR haplotypes, SNP haplotypes were determined using 10 critical polymorphisms. The entire gene was screened sequentially by protein truncation testing (PTT), single strand conformation polymorphism (SSCP), and then denaturing high performance liquid chromatography (dHPLC) to identify the disease-causing mutations. Of the expected 54 mutations, 50 were identified. All mutations but one, led to a truncated or null form of the ATM protein (nonsense, splice site, or frameshift). Five families (18.5%) carried a deletion of 3450nt (from IVS28 to Ex31), making this one of the two most common Brazilian mutations. Mutations were located throughout the entire gene, with no clustering or hotspots. Standardized STR haplotype analysis greatly enhanced the efficiency of mutation screening. 相似文献
42.
Norgauer J Ibig Y Gmeiner D Herouy Y Fiebich BL 《International journal of molecular medicine》2003,12(1):83-86
Prostaglandin E2 (PGE2), which is generated by the enzymatic activity of cyclooxygenase-1 and -2 (COX-1/2), plays a central role in the maturation process of dendritic cells (DC). Since regulation of COX-1/2 expression in human DC is only partially understood, we addressed the expression and activity of COX-1/2 in these cells. Here we show that lipopolysaccharide (lps) induces COX-2 mRNA and protein synthesis as well as the release of PGE2 in human interleukin-4 and granulocyte/macrophage colony-stimulating factor-differentiated monocyte-derived DC cultivated in the presence of 1% human plasma. Moreover, we found that lps induces p38 stress-activated protein kinase (p38) in these cells and inhibitors of p38 blocked lps-induced COX-2 expression and activity. Our data indicate that during lps-induced maturation p38 regulates COX-2 expression and PGE2 synthesis in DC. 相似文献
43.
A new autosomal recessive syndrome of characteristic facies, joint contractures, skeletal abnormalities, and normal development: second report with further clinical delineation 下载免费PDF全文
Ajay Gupta Christine M Hall Yvonne F Ransley Victoria A Murday 《Journal of medical genetics》1995,32(10):809-812
We describe a girl of Pakistani origin, born to consanguineous parents, with a multiple congenital anomaly (MCA) syndrome. This is the second report confirming an apparently new autosomal recessive syndrome reported earlier by van den Ende et al in 1992. The hallmarks of this MCA syndrome include characteristic facies with blepharophimosis, narrow, beaked nose, hypoplastic maxilla with or without cleft palate and everted lower lip, arachnodactyly, self-limiting congenital joint contractures, peculiar skeletal abnormalities, and normal growth and development. Further clinical and radiological delineation of the syndrome in this report suggests that the term “Marden-Walker-like syndrome without psychomotor retardation”, used in the first report to describe this condition, does not accurately reflect its clinical picture. The overall prognosis in this syndrome seems good. 相似文献
44.
Soy isoflavones, body composition, and physical performance 总被引:2,自引:0,他引:2
OBJECTIVES: Physiologic changes, occurring during the process of aging, can have serious health consequences, such as increased risk of chronic disease and disability. Decline in estradiol levels after menopause is hypothesized to contribute to this risk. Thus, hormone therapy (HT) might prevent or delay those changes. However, HT has serious side effects and alternative approaches are needed. METHODS: We performed a 12-month double-blind randomized trial comparing soy protein containing 99mg isoflavones (aglycone weights) with milk protein (placebo) daily in 202 postmenopausal women aged 60-75 years. Endpoints were body composition, and physical performance. Randomization resulted in reasonable well-balanced groups, 153 (76%) women completed the trial. Compliance was good (plasma genistein levels 55 +/- 101 and 1259 +/- 1610 nmol/L for placebo and soy group, respectively). The changes in the endpoints during the intervention period among the two intervention groups were analyzed. RESULTS: Body mass index (BMI) and waist-to-hip ratio did not change during intervention. Handgrip strength at the final visit was slightly worse in the soy group compared to the placebo group (-0.45 kg (95% C.I.: -2.5, 1.6 kg; p = 0.7), but this difference was not statistically significant. Self-reported functional status, mobility and physical performance, all slightly improved during intervention but there were no differences between the groups. CONCLUSIONS: The results of the present trial do not support the view that soy isoflavones have favorable effects on body composition and physical performance in postmenopausal women. 相似文献
45.
Chondroconductive potential of tantalum trabecular metal 总被引:2,自引:0,他引:2
Gordon WJ Conzemius MG Birdsall E Wannemuehler Y Mallapragada S Lewallen DG Yaszemski MJ O'Driscoll SW 《Journal of biomedical materials research. Part B, Applied biomaterials》2005,75(2):229-233
Mesenchymal stem cells or chondrocytes have been implanted into joints in biodegradable matrices in order to improve the quality of healing cartilage defects; however, insufficient biomechanical strength of the construct at implantation is a limiting factor for clinical application. Logically, a construct with better biomechanical characteristics would provide better results. Tantalum trabecular metal (TTM) is osteoconductive and mechanically similar to subchondral bone. The objective of this pilot study was to determine if TTM is also chondroconductive. Small sections of TTM were cultured with emu and canine chondrocytes in static and dynamic culture environments. The sections cultured in dynamic bioreactors were diffusely covered with a cartilaginous matrix. Sections cultured in static conditions had no growth. Histologic evaluation from emu and canine dynamic cultures showed tissue that was heavily populated with mesenchymal cells that resembled chondrocytes, and glycosaminoglycan staining that was distributed throughout the matrix. Type II collagen content in the canine dynamic culture was 84% by SDS-PAGE. Tantalum trabecular metal is chondroconductive in vitro in a dynamic environment when cultured with adult canine or emu chondrocytes. This technology could be expanded to determine if cartilaginous-metallic constructs may be used for joint resurfacing of osteoarthritic joints. 相似文献
46.
Hippocampal metabolic abnormalities in mild cognitive impairment and Alzheimer's disease 总被引:3,自引:0,他引:3
Mild cognitive impairment (MCI) defines a group of otherwise healthy elderly subjects with a markedly elevated risk of developing Alzheimer's disease (AD). In the search for biomarkers of MCI, we assessed whether MCI shares neurochemical abnormalities with AD in areas affected early in the course of the disease. As a secondary study aim, we tested to what extent neurochemical findings reflect neuropsychological deficits. Proton spectroscopy was performed in 19 MCI patients, 18 AD patients and 22 age and gender matched controls (CON) within the parietal gray and white matter (PWM and PGM) and the hippocampus (HIP). The cognitive test battery used included measures compiled by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD). The N-acetyl-aspartate to creatine ratio (NAA/Cr) was significantly reduced in the HIP of MCI and AD compared with CON (p < 0.05). Only AD patients showed parietal abnormalities, namely significantly elevated myoinositol (mI/Cr and mI/NAA) in PGM, reduced NAA/Cr and elevated mI/NAA in PWM. MCI subjects were significantly impaired in categorical verbal fluency (VF) (p < 0.001) and delayed verbal recall (DVR) (p < 0.001). VF was positively correlated with hippocampal NAA/Cr (p < 0.05) and parietal mI/NAA (p < 0.05). In summary, this study demonstrates shared neurobiological hippocampal abnormalities in MCI and AD, whereas parietal lobe neurochemical profiles and functions were normal in MCI. Thus, biological evidence is provided that MCI represents a precursor stage of AD. Moreover, multivoxel 1H MRS may enable an objective staging of the neurodegenerative process underlying the age-dependent cognitive deficits eventually leading to dementia. 相似文献
47.
Recognition surfaces of MHC class I 总被引:1,自引:0,他引:1
Summary: Recent crystallographic results have provided dose to atomic resolution views of the recognition events mediated by MHC class I molecules. The specificity-conferring interaction of MHC class I/peptide with a T-cell antigen receptor (TCR) appears dependent on certain key interactions with the MHC scaffold. These interactions, in particular those of the TCR Va domain, define a standard orientation for TCR binding. Previous studies on biologically significant variations in the TCR recognition surface presented by a series of MHC/variant peptide complexes can be reassessed in the light of this TCR-building mode. The interaction of CDS with MHC class I resembles that between antibody and antigen in the use of loops from the CD8 structure. The interaction is of very low affinity and buries equivalent surface area to that between the TCR and MHC class I but while the TCR/MHC interface shows poor surface shape complementarity the match in the conservative interaction between MHC and CDS is precise. 相似文献
48.
Hepatitis C infection among injecting drug users in general practice: a cluster randomised controlled trial of clinical guidelines'' implementation 下载免费PDF全文
Walter Cullen June Stanley Deirdre Langton Yvonne Kelly Anthony Staines Gerard Bury 《The British journal of general practice》2006,56(532):848-856
BACKGROUND: Hepatitis C is a common infection among injecting drug users and has important implications for general practice. Although several clinical guidelines concerning the infection have been published, their effectiveness has yet to be tested. AIM: To assess the effectiveness of a general practice-based complex intervention to support the implementation of clinical guidelines for hepatitis C management among current or former drug users attending general practice. DESIGN OF STUDY: Cluster randomised controlled trial. SETTING: General practices in the Eastern Regional Health Authority area of Ireland. METHOD: Twenty-six practices were randomly allocated within strata to receive the intervention under study or to provide care as usual for a period of 6 months. There was screening for patients attending general practice for methadone maintenance treatment for hepatitis C and referral of anti-HCV antibody positive patients to a specialist hepatology department for assessment. RESULTS: At study completion, patients in the intervention group were significantly more likely to have been screened for hepatitis C than those in the control group, odds ratio adjusted for clustering 3.76 (95% confidence interval [CI] = 1.3 to 11.3) and this association remained significant after adjusting for other potentially confounding variables, using multiple logistic regression, with the odds ratio adjusted for clustering 4.53 (95% CI = 1.39 to 14.78). Although anti-HCV antibody positive patients in the intervention group were more likely to have been referred to a hepatology clinic, this was not statistically significant (P = 0.06). CONCLUSION: General practice has an important role in the care of people at risk of hepatitis C and when appropriately supported can effectively implement current best practice. 相似文献
49.
50.
Yvonne Severne Louis Kanarek Georges Vauquelin 《Naunyn-Schmiedeberg's archives of pharmacology》1986,332(3):247-252
Summary Agonist and antagonist binding characteristics of -adrenoceptors in turkey erythrocyte ghosts were determined at different temperatures ranging between 7°C and 42°C. [3H]-DHA saturation binding experiments revealed that the antagonist-receptor interaction is entropy-driven with a small enthalpic contribution. Isoproterenol/[3H]-DHA competition binding followed the law of mass action at all the investigated temperatures. The agonist-receptor interaction is enthalpy driven with a small unfavorable decrease in entropy. This is consistent with the agonist's ability to favor an endoenergetic transconformation of the receptors.Only part of the agonist-bound receptors can undergo functional coupling to the stimulatory component of the adenylate cyclase system (Ns). This coupling process is associated with locking-in of the agonist and becomes persistent in the presence of the alkylating reagent N-ethylmaleimide. The number of agonist/N-ethylmaleimide-sensitive sites (i.e. coupling-prone receptors) increases with the temperature until it reaches a plateau value of 50% between 27–32°C. Qualitatively similar data were obtained for rat lung and turkey erythrocyte membranes. These observations suggest that the whole receptor population can undergo agonist-mediated conformational changes but that only part of them can couple to Ns. 相似文献