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61.
Irene Paganini Vivian Y Chang Gabriele L Capone Jeremie Vitte Matteo Benelli Lorenzo Barbetti Roberta Sestini Eva Trevisson Theo JM Hulsebos Marco Giovannini Stanley F Nelson Laura Papi 《European journal of human genetics : EJHG》2015,23(7):963-968
Schwannomatosis is characterized by the development of multiple non-vestibular, non-intradermal schwannomas. Constitutional inactivating variants in two genes, SMARCB1 and, very recently, LZTR1, have been reported. We performed exome sequencing of 13 schwannomatosis patients from 11 families without SMARCB1 deleterious variants. We identified four individuals with heterozygous loss-of-function variants in LZTR1. Sequencing of the germline of 60 additional patients identified 18 additional heterozygous variants in LZTR1. We identified LZTR1 variants in 43% and 30% of familial (three of the seven families) and sporadic patients, respectively. In addition, we tested LZTR1 protein immunostaining in 22 tumors from nine unrelated patients with and without LZTR1 deleterious variants. Tumors from individuals with LZTR1 variants lost the protein expression in at least a subset of tumor cells, consistent with a tumor suppressor mechanism. In conclusion, our study demonstrates that molecular analysis of LZTR1 may contribute to the molecular characterization of schwannomatosis patients, in addition to NF2 mutational analysis and the detection of chromosome 22 losses in tumor tissue. It will be especially useful in differentiating schwannomatosis from mosaic Neurofibromatosis type 2 (NF2). However, the role of LZTR1 in the pathogenesis of schwannomatosis needs further elucidation. 相似文献
62.
Associations of chemokine system polymorphisms with clinical outcomes and treatment responses of chronic hepatitis C 总被引:21,自引:0,他引:21
Promrat K McDermott DH Gonzalez CM Kleiner DE Koziol DE Lessie M Merrell M Soza A Heller T Ghany M Park Y Alter HJ Hoofnagle JH Murphy PM Liang TJ 《Gastroenterology》2003,124(2):352-360
BACKGROUND & AIMS: CCR5Delta32, a 32-base pair deletion of the CC chemokine receptor (CCR) 5 gene, is associated with slowed human immunodeficiency virus disease progression in heterozygotes and protection against infection in homozygotes. A recent study found a higher than expected frequency of CCR5Delta32/Delta32 in patients with hepatitis C virus infection. The roles of other disease-associated chemokine system polymorphisms have not been evaluated in hepatitis C virus infection. METHODS: Six chemokine system polymorphisms (CCR5Delta32, CCR5 promoter 59029-G/A, CCR2 -64I, RANTES [regulated upon activation, normal T cells expressed and secreted] -403 -G/A, and -28 -C/G and stromal derived factor 1 -3'A) were studied in 417 patients with liver diseases (339 with hepatitis C) and 2380 blood donors. The clinical parameters of hepatitis C virus infection were compared between carriers and noncarriers of each genetic variant. RESULTS: The frequency of CCR5Delta32 homozygosity was 0.8% in whites with hepatitis C virus and 1.1% in controls (P = 0.75). The CCR5Delta32 allele was not associated with any of the clinical parameters of hepatitis C virus infection. Hepatitis C virus-seropositive whites with the RANTES -403-A allele were less likely to have severe hepatic inflammation compared with those without (odds ratio, 0.34; P = 0.03). In multivariate analysis, the CCR5 promoter 59029 -A allele was marginally associated with a sustained response to interferon therapy (odds ratio, 3.07; P = 0.048). CONCLUSIONS: In this cohort, the frequency of CCR5Delta32 homozygosity in patients with hepatitis C was similar to controls. The high prevalence of CCR5Delta32 homozygosity in the hepatitis C virus patients of the earlier study likely reflects resistance to human immunodeficiency virus infection in hemophiliacs rather than a susceptibility to hepatitis C virus infection. Expression of CCR5 and RANTES may be important in the modulation of hepatic inflammation and response to interferon therapy in chronic hepatitis C. 相似文献
63.
Yoon Gi Choi Theo W Dreher A L N Rao 《Proceedings of the National Academy of Sciences of the United States of America》2002,99(2):655-660
tRNAs, the adapter molecules in protein synthesis, also serve as metabolic cofactors and as primers for viral RNA-directed DNA synthesis. The genomic and subgenomic RNAs of some plant viruses have a 3'-terminal tRNA-like structure (TLS) that can accept a specific amino acid and serve as a site for initiation of replication and as a simple telomere. We report a previously undescribed role for the TLS of brome mosaic virus (BMV), and potentially for cellular tRNA, in mediating the assembly of its icosahedral virions. BMV genomic RNAs and subgenomic RNA lacking the TLS failed to assemble into virions when incubated with purified BMV coat protein. Assembly was restored by addition of a 201-nt RNA containing the BMV TLS. TLSs from two other plant viruses as well as tRNAs from wheat germ and yeast were similarly active in the BMV virion assembly reaction, but ribosomal RNA and polyadenylate did not facilitate assembly. Surprisingly, virions assembled from TLS-less BMV RNA in the presence of tRNAs or TLS-containing short RNA did not incorporate the latter molecules. Consistent with a critical role for the BMV TLS in virion assembly, mutations in the BMV genomic RNAs that were designed to disrupt the folding of the TLS also abolished virion assembly. We discuss the likely roles of the TLS in early stages of virion assembly. 相似文献
64.
OBJECTIVES. This study examines the association of hearing impairment and chronic diseases (diabetes mellitus, lung disease, cardiac disease, stroke, cancer, peripheral artery disease, osteoarthritis, rheumatoid arthritis) with psychosocial status (depression, self-efficacy, mastery, loneliness, social network size) in older persons. METHODS. The sample consists of 3,107 persons (55 to 85 years) participating in the Longitudinal Aging Study Amsterdam. MANOVA, adjusted for covariates, was used to test the effect of hearing impairment on the combined outcomes. The association of hearing impairment and chronic diseases with psychosocial status was studied using multivariate regression analyses. RESULTS. Hearing impaired elderly report significantly more depressive symptoms, lower self-efficacy and mastery, more feelings of loneliness, and a smaller social network than normally hearing peers. Whereas chronic diseases show significant associations with some outcomes, hearing impairment is significantly associated with all psychosocial variables. DISCUSSION. The findings emphasize the negative effect of hearing impairment on quality of life. 相似文献
65.
Soza A Heller T Ghany M Lutchman G Jake Liang T Germain J Hsu HH Park Y Hoofnagle JH 《Journal of hepatology》2005,43(1):67-71
BACKGROUND/AIMS: Currently, there are no effective therapies available for patients with chronic hepatitis C who have failed to respond to optimal interferon alfa-based regimens. The aims of this pilot study were to assess the antiviral activity and safety of interferon gamma in chronic hepatitis C. METHODS: Patients with chronic hepatitis C, genotype 1, who had not responded to or who had relapsed after therapy with interferon alfa and ribavirin were enrolled in a trial of interferon gamma 1b given in doses of 100, 200 or 400 microg subcutaneously three times weekly for 4 weeks. Frequent blood samples were obtained for HCV RNA levels. RESULTS: Fourteen patients were enrolled. Geometric mean HCV RNA levels remained unchanged. Serum aminotransferase levels also did not change, while there were significant decreases in neutrophil counts (-41% from baseline) and hematocrit (-5%). Low grade fever and malaise were common with the first injection of interferon gamma, but no serious side effects were encountered. CONCLUSIONS: Although relatively well tolerated, interferon gamma in doses of 100-400 microg thrice weekly had no effect on HCV RNA levels in patients with chronic hepatitis C who had failed to achieve a sustained response to interferon alfa-based therapies. 相似文献
66.
The social ecology of girls' bullying practices: exploratory research in two London schools
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Farah Jamal Chris Bonell Angela Harden Theo Lorenc 《Sociology of health & illness》2015,37(5):731-744
This exploratory study adopts a socio‐ecological approach to examine the context of school bullying. It asks: (1) what are students' accounts of bullying practices?; (2) how are these enabled and constrained by the school‐environment?; (3) how is gender implicated? Qualitative data were collected from girls in two schools in London via focus groups (one in each school; students aged 12‐15) and seven semi‐structured interviews (in one school; students aged 16‐18); and from school policy documents. Our interpretation of girls' accounts, informed by Giddens' structuration theory, suggests that bullying practices were spatially patterned in the schools and often characterised by the regulation of girls' sexuality and sexual‐harassment. Repeated acts of aggression were fluid with regard to the bully and victim role, challenging the dominant view of bullying as characterised by consistent disparities in power between individuals. Schools structured bullying behaviour via policies and practices that ignored these forms of abuse and which focused on and may have been complicit in the making of stable ‘bully’ and ‘victim’ roles, thus indirectly contributing to the reproduction of unhealthy relationships between students. In terms of gender, traditional gendered and sexual discourses appear to structure the identities of the schools and girls in our study. 相似文献
67.
Junling Wang Ya-Chen Tina Shih Yolanda Qin Theo Young Zachary Thomas Christina A. Spivey David K. Solomon Marie Chisholm-Burns 《American Health & Drug Benefits》2015,8(5):247-255
Background
To increase the enrollment rate of medication therapy management (MTM) programs in Medicare Part D plans, the US Centers for Medicare & Medicaid Services (CMS) lowered the allowable eligibility thresholds based on the number of chronic diseases and Part D drugs for Medicare Part D plans for 2010 and after. However, an increase in MTM enrollment rates has not been realized.Objectives
To describe trends in MTM eligibility thresholds used by Medicare Part D plans and to identify patterns that may hinder enrollment in MTM programs.Methods
This study analyzed data extracted from the Medicare Part D MTM Programs Fact Sheets (2008–2014). The annual percentages of utilizing each threshold value of the number of chronic diseases and Part D drugs, as well as other aspects of MTM enrollment practices, were analyzed among Medicare MTM programs that were established by Medicare Part D plans.Results
For 2010 and after, increased proportions of Medicare Part D plans set their eligibility thresholds at the maximum numbers allowable. For example, in 2008, 48.7% of Medicare Part D plans (N = 347:712) opened MTM enrollment to Medicare beneficiaries with only 2 chronic disease states (specific diseases varied between plans), whereas the other half restricted enrollment to patients with a minimum of 3 to 5 chronic disease states. After 2010, only approximately 20% of plans opened their MTM enrollment to patients with 2 chronic disease states, with the remaining 80% restricting enrollment to patients with 3 or more chronic diseases.Conclusion
The policy change by CMS for 2010 and after is associated with increased proportions of plans setting their MTM eligibility thresholds at the maximum numbers allowable. Changes to the eligibility thresholds by Medicare Part D plans might have acted as a barrier for increased MTM enrollment. Thus, CMS may need to identify alternative strategies to increase MTM enrollment in Medicare plans. 相似文献68.
69.
70.
Shi Hong Kai Chook Shaun Leow Lowell Lim Shir Lynn Ramanathan Kollengode Kofidis Theo Kang Giap Swee 《Journal of thrombosis and thrombolysis》2021,52(2):680-682
Journal of Thrombosis and Thrombolysis - We present a novel case of a patient with nephrotic syndrome and previous left pneumonectomy who had a massive pulmonary embolism of his remnant right... 相似文献