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91.
Association of a nonsense mutation (W1282X), the most common mutation in the Ashkenazi Jewish cystic fibrosis patients in Israel, with presentation of severe disease 总被引:8,自引:6,他引:8 下载免费PDF全文
Tzipora Shoshani Arie Augarten Ephraim Gazit Nurit Bashan Yaakov Yahav Yosef Rivlin Asher Tal Hagit Seret Liora Yaar Eitan Kerem Bat-sheva Kerem 《American journal of human genetics》1992,50(1):222-228
Only about 30% of the cystic fibrosis chromosomes in the Israeli cystic fibrosis patient populations carry the major CF mutation (delta F508). Since different Jewish ethnic groups tended to live as closed isolates until recent times, high frequencies of specific mutations are expected among the remainder cystic fibrosis chromosomes of these ethnic groups. Genetic factors appear to influence the severity of the disease. It is therefore expected that different mutations will be associated with either severe or mild phenotype. Direct genomic sequencing of exons included in the two nucleotide-binding folds of the putative CFTR protein was performed on 119 Israeli cystic fibrosis patients from 97 families. One sequence alteration which is expected to create a termination at residue 1282 (W1282X) was found in 63 chromosomes. Of 95 chromosomes, 57 (60%) are of Ashkenazi origin. Together with the delta F508 (23% in this group), G542X, N1303K, and 1717-1G----A mutations, the identification of 92% of cystic fibrosis chromosomes of Ashkenazi origin becomes possible. Patients homozygous for the W1282X mutation (n = 16) and patients heterozygous for the delta F508 and W1282X mutations (n = 22) had similarly severe disease, reflected by pancreatic insufficiency, high incidence of meconium ileus (37% and 27%, respectively), early age at diagnosis, poor nutritional status, and variable pulmonary function. In conclusion, the W1282X mutation is the most common cystic fibrosis mutation in the Ashkenazi Jewish patient population in Israel. This nonsense mutation is associated with presentation of severe disease. 相似文献
92.
The KCNQ1 (Kv7.1) COOH terminus, a multitiered scaffold for subunit assembly and protein interaction 总被引:2,自引:0,他引:2
Wiener R Haitin Y Shamgar L Fernández-Alonso MC Martos A Chomsky-Hecht O Rivas G Attali B Hirsch JA 《The Journal of biological chemistry》2008,283(9):5815-5830
The Kv7 subfamily of voltage-dependent potassium channels, distinct from other subfamilies by dint of its large intracellular COOH terminus, acts to regulate excitability in cardiac and neuronal tissues. KCNQ1 (Kv7.1), the founding subfamily member, encodes a channel subunit directly implicated in genetic disorders, such as the long QT syndrome, a cardiac pathology responsible for arrhythmias. We have used a recombinant protein preparation of the COOH terminus to probe the structure and function of this domain and its individual modules. The COOH-terminal proximal half associates with one calmodulin constitutively bound to each subunit where calmodulin is critical for proper folding of the whole intracellular domain. The distal half directs tetramerization, employing tandem coiled-coils. The first coiled-coil complex is dimeric and undergoes concentration-dependent self-association to form a dimer of dimers. The outer coiled-coil is parallel tetrameric, the details of which have been elucidated based on 2.0 A crystallographic data. Both coiled-coils act in a coordinate fashion to mediate the formation and stabilization of the tetrameric distal half. Functional studies, including characterization of structure-based and long QT mutants, prove the requirement for both modules and point to complex roles for these modules, including folding, assembly, trafficking, and regulation. 相似文献
93.
Ronit Pinkas-Kramarski Reuven Stein Liora Lindenboim Mordechai Sokolovsky 《Journal of neurochemistry》1992,59(6):2158-2166
Rat pheochromocytoma (PC12) cells stably expressing cloned m1 muscarinic acetylcholine receptors (PC12M1) undergo morphological changes when stimulated by muscarinic agonists. These changes, which include the outgrowth of neurite-like processes, are blocked by the muscarinic antagonist atropine and are not observed in PC12 cells. The observed morphological changes, which are independent of RNA and protein synthesis, are blocked by the methylation inhibitor 5'-deoxy-5'-methylthioadenosine, suggesting that methylation plays a role in this process. Analysis of cyclic AMP accumulation and phosphoinositide turnover reveals that both processes are enhanced on activation by muscarinic agonist. Our data suggest, however, that the muscarinic-dependent neurite-like outgrowth processes are not mediated by cyclic AMP, Ca2+, or protein kinase C pathways. The muscarinic-dependent neurite outgrowth effect is enhanced by nerve growth factor, with a resulting increase in both the number of neurite-extending cells and the length of the neurite. In addition, activation of muscarinic receptors in PC12M1 cells stimulates the induction of marker genes for neuronal differentiation. Muscarinic receptors may therefore mediate growth factor-like effects in these cells. 相似文献
94.
Tal Oron Avihu Krieger Michal Yakobovich-Gavan Ariel Tenenbaum Rotem Diamant Moshe Phillip Liora Lazar 《Endocrine practice》2022,28(1):36-43
ObjectiveGiven the large number of false-positive growth hormone deficiency (GHD) diagnoses from a single growth hormone (GH) stimulation test in children, 2 different pharmacologic tests, performed on separate days or sequentially, are required. This study aimed to assess the reliability and safety of a combined arginine-clonidine stimulation test (CACST).MethodsThis was a retrospective, single-center, observational study. During 2017-2019, 515 children aged >8 years underwent GH stimulation tests (CACST: n = 362 or clonidine stimulation test [CST]: n = 153). The main outcome measures used to compare the tests were GH response (sufficiency/deficiency) and amplitude and timing of peak GH and safety parameters.ResultsPopulation characteristics were as follows: median age of 12.2 years (interquartile range [IQR]: 10.7, 13.4), 331 boys (64%), and 282 prepubertal children (54.8%). The GHD rate was comparable with 12.7% for CACST and 14.4% for CST followed by a confirmatory test (glucagon or arginine) (P = .609). Peak GH was higher and occurred later in response to CACST compared with CST (14.6 ng/mL [IQR: 10.6, 19.4] vs 11.4 ng/mL [IQR: 7.0, 15.8], respectively, P < .001; 90 minutes [IQR: 60, 90] vs 60 minutes [IQR: 60, 90], respectively, P < .001). No serious adverse events occurred following CACST.ConclusionOur findings demonstrate the reliability and safety of CACST in detecting GHD in late childhood and adolescence, suggesting that it may replace separate or sequential GH stimulation tests. By diminishing the need for the second GH stimulation test, CACST saves time, is more cost-effective, and reduces discomfort for children, caregivers, and medical staff. 相似文献
95.
A carrier for entomopathogenic nematodes based on an edible-to-insects calcium alginate gel was developed. The alginate system was produced by external setting through an interaction between an aqueous sodium alginate mixture and calcium ions under acidic conditions. Sodium hexa-metaphosphate was used to control gel formation. Yeast extract used in the gel as a phagostimulant for Spodoptera littoralis larvae improved the insect's relative consumption rate and digestibility. The nematodes in the gel effectively controlled the larvae in a 24-h leaf bioassay, although nematode survival in the gel was ~ 50%. Gels subjected to 31% relative humidity (RH) prior to larval feeding became desiccated and were inedible to insects. However, gels at 61% RH supported larval feeding, although the water loss from the gel due to evaporation from 200-400-mg gel cubes at this humidity exceeded 50%. The gel might be a useful delivery system for nematodes against insects infesting the plant canopy in greenhouses. 相似文献
96.
Liat de Vries Michal Baum Michal Horovitz Moshe Phillip Galia Barash Orit Pinhas-Hamiel Liora Lazar 《Endocrine practice》2022,28(1):44-51
ObjectiveTo compare clinical outcomes of 3 treatment regimens—glucocorticoids (GCs), oral contraceptives (OCs), or a combination of both—administered to adolescents and young women diagnosed in childhood with nonclassical congenital adrenal hyperplasia (NCCAH), who had been treated with GCs until their adult height was achieved.MethodsA retrospective study of medical records of 53 female patients with NCCAH followed in 3 tertiary pediatric endocrinology institutes. The 3 treatment groups were compared for the prevalence of hirsutism and acne, standardized body mass index (BMI)-standard deviation score (SDS), and androgen levels at the attainment of adult height (baseline), 1-year later, and at the last documented visit.ResultsAt baseline, there were no significant differences among groups in BMI-SDS, androgen levels, hirsutism prevalence, acne, or irregular menses. From baseline to the last visit, the rate of hirsutism declined significantly only in the OC group (37.5% vs 6.2%, respectively; P = .03). The rate of acne declined in the combined group (50% vs 9%, respectively; P = .03) with a similar tendency in the OC group (50% vs 12.5%, respectively; P = .05). No significant changes were observed in BMI-SDS for the entire cohort or any subgroup during follow-up. A significant rise in androstenedione (P < .001), testosterone (P < .01), and 17-hydroxyprogesterone (P < .01) levels was observed only in the OC group.ConclusionIn girls diagnosed in childhood with NCCAH, who require treatment for hyperandrogenism following completion of linear growth, management should be tailored individually using a patient-centered approach. Treatment with OCs might be better than that with GCs for regression of hirsutism and acne. The long-term effects of elevated levels of androgens associated with this treatment regimen should be further studied. 相似文献
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98.
Liora Cahalon Rami Hershkovz Dalia Gilat Ariel Miller Steven K. Akiyama Kenneth M. Yamada Ofer Lider 《Cell communication & adhesion》1994,2(3):269-273
The ECM is composed of various cell-adhesive glycoproteins, such as, fibronectin (FN), laminin (LN), and different types of glycosaminoglycans and proteoglycans. These building blocks of the ECM are linked together to form a dense and complex tissue that fills the interstitial spaces and comprises the boundaries between cells and tissues. The ECM is the major milieu in which immune cells function during inflammatory processes (Shimizu and Shaw, 1991; Yamada, 1991). Recognition of ECM-glycoproteins by immune cells is mediated by very late activation (VLA) receptors, also referred to as integrins of the β1-subfamily (Hynes, 1992). A prerequisite of lymphocyte-ECM interactions is activation of the cells by mitogens, or via their CD3-T cell receptor complex, either of these types of activation modulates the affinity of otherwise inactive β1-integrins (Shimizu, et al., 1990). 相似文献