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991.
W‐H Chien SS‐F Gau Y‐Y Wu Y‐S Huang J‐S Fang Y‐J Chen W‐T Soong Y‐N Chiu C‐H Chen 《Clinical genetics》2010,78(5):449-456
Chien W‐H, Gau SS‐F, Wu Y‐Y, Huang Y‐S, Fang J‐S, Chen Y‐J, Soong W‐T, Chiu Y‐N, Chen C‐H. Identification and molecular characterization of two novel chromosomal deletions associated with autism. Autism is a childhood‐onset neurodevelopmental disorder with a strong genetic basis in its etiology. Conventional karyotype analysis has revealed that chromosomal structural aberrations such as translocation, inversion, deletion, and duplication play a role in causing autism spectrum disorders (ASD). In addition, recent array‐based comparative genomic hybridization (array CGH) studies discovered that submicroscopic deletion and duplication of DNA segments also contributed significantly to the genetic etiology of ASD. Together, these studies indicate that genomic rearrangement is an important genetic mechanism of ASD. Using karyotyping analysis and array CGH technology, we identified a subtelomeric deletion of approximately 6.8 Mb at 4q35.1‐35.2 and a terminal deletion of approximately 2.4 Mb at 8p23.2‐pter in two autistic boys, respectively. These two deletions were further validated using fluorescent in situ hybridization and real‐time quantitative polymerase chain reaction, and their breakpoints were delineated using high‐resolution array CGH. The 4q deletion is a rare de novo mutation, while the transmission of 8p deletion is unknown, because the father of the patient was unavailable for study. These two deletions are rare mutations and were not found in the additional 282 patients with ASD and in the 300 control subjects in our population. The identification of these two chromosomal deletions contribute to our understanding of the genetic basis of ASD, and the haploinsufficiency of several genes located at the deleted regions of chromosome 8p and 4q may contribute to the clinical phenotypes of autism. 相似文献
992.
993.
Khairul MF Min TH Low JH Nasriyyah CH A'shikin AN Norazmi MN Ravichandran M Raju SS 《Japanese journal of infectious diseases》2006,59(5):329-331
Fluoxetine (FLX), a P-glycoprotein inhibitor with antimalarial activity, is promising candidate for reversing chloroquine/mefloquine (CQ/MQ) resistance. The Dd2 strain of CQ- and MQ-resistant Plasmodium falciparum was synchronized and assayed with various concentrations of CQ/MQ individually and in combination with FLX or verapamil (VPL). Our results indicated the 50% inhibitory concentration values of CQ and MQ were greatly lowered when FLX was used simultaneously. Isobolograms indicated that CQ-FLX combinations are more synergistic (mean fractional inhibitory concentration [FIC] index 0.55) than MQ-FLX (mean FIC index 0.64), and their synergistic effect was better than or at par with CQ-VPL (mean FIC index 0.88) and MQ-VPL (mean FIC index 0.60) combinations. We conclude that the FLX potentiates the CQ and MQ response on multidrug-resistant P. falciparum at clinically achievable concentrations. 相似文献
994.
Climbers at high altitude (>5000 m) lose weight. This impairs performance and safety, but the mechanisms are not entirely due to an imbalance between energy intake and expenditure. There is some evidence of carbohydrate malabsorption, but there are also changes in fat metabolism and total body water. This paper considers the physiological control of weight and then discusses the changes in each parameter before addressing the practical implications. 相似文献
995.
996.
BACKGROUND: The HIV protease inhibitor (PI) atazanavir does not impair insulin sensitivity acutely but ritonavir and lopinavir induce insulin resistance at therapeutic concentrations. OBJECTIVE: To test the hypothesis that atazanavir combined with a lower dose of ritonavir would have significantly less effect on glucose metabolism than lopinavir/ritonavir in vitro and clinically. METHODS: Glucose uptake was measured following insulin stimulation in differentiated human adipocytes in the presence of ritonavir (2 micromol/l) combined with either atazanavir or lopinavir (3-30 micromol/l). These data were examined clinically using the hyperinsulinemic euglycemic clamp and oral glucose tolerance testing (OGTT) in 26 healthy HIV-negative men treated with atazanavir/ritonavir (300/100 mg once daily) and lopinavir/ritonavir (400/100 mg twice daily) for 10 days in a randomized cross-over study. RESULTS: Atazanavir inhibited glucose uptake in vitro significantly less than lopinavir and ritonavir at all concentrations. Ritonavir (2 micromol/l) combined with either atazanavir or lopinavir (3-30 micromol/l) did not further inhibit glucose uptake. During euglycemic clamp, there was no significant change from baseline insulin sensitivity with atazanavir/ritonavir (P = 0.132), while insulin sensitivity significantly decreased with lopinavir/ritonavir from the baseline (-25%; P < 0.001) and from that seen with atazanavir/ritonavir (-18%; P = 0.023). During OGTT, the HOMA insulin resistance index significantly increased from baseline at 120 min with atazanavir/ritonavir and at 150 min with lopinavir/ritonavir. The area under the curve of glucose increased significantly with lopinavir/ritonavir but not with atazanavir/ritonavir. CONCLUSIONS: Both glucose uptake in vitro and clinical insulin sensitivity in healthy volunteers demonstrate differential effects on glucose metabolism by the combination PI atazanavir/ritonavir and lopinavir/ritonavir. 相似文献
997.
Women from Pakistan and India are more often diagnosed with early-onset breast cancer than Caucasian women. Given that only 12% of Pakistani women diagnosed with breast cancer at or before 30 years of age have previously been shown to harbor germ line mutations in the breast cancer susceptibility genes BRCA1 and BRCA2, the genetic causes of the majority of early-onset cases are unexplained. Since germ line mutations in the tumor suppressor gene TP53 predispose women to early-onset breast cancer, we assessed the prevalence of TP53 mutations in 105 early-onset breast cancer patients from Pakistan, who had previously been found to be negative for BRCA1 and BRCA2 germ line mutations. The patient group included 67 women diagnosed with early-onset breast cancer at or before age 30 with no family history of breast or ovarian cancer (EO30NFH group) and 38 women diagnosed with breast cancer at or before age 40 with one or more first- or second-degree relatives with breast or ovarian cancer (EO40FH group). Mutation analysis of the complete TP53 coding region was performed using denaturing high-performance liquid chromatography analysis, followed by DNA sequencing of variant fragments. One deleterious mutation, c.499-500delCA in exon 5, was identified in the 105 breast cancer patients (1%). This mutation is novel in the germ line and has not been described in other populations. It was detected in a 28-year-old patient with no family history of breast or ovarian cancer. This mutation is rare as it was not detected in additional 157 recently recruited non-BRCA1 and non-BRCA2-associated early-onset breast cancer patients. Our findings show that TP53 mutations may account for a minimal portion of early-onset breast cancer in Pakistan. 相似文献
998.
Sireesha Vaidya Noor Ahmad Shaik Madhavi Latha Srinivas Chava Khaliq Mohiuddin Annapurna Yalla Kaipa Prabhakar Rao Vijaya Lakshmi Kodati Qurratulain Hasan 《Tumour biology》2012,33(5):1411-1418
Fumarate hydratase (FH) gene is reported to have specific involvement in syndromic uterine tumors, but its role in nonsyndromic forms is still unclear. Hence, the present study has aimed to screen the role of promoter methylation status and mutations in exon 2 and 7 regions of FH gene in the genesis of nonsyndromic uterine leiomyomas. Leiomyoma and myometrium tissues were collected from 85 hysterectomized uterine specimens. DNA from each of the biopsy was subjected to PCR, methylation-specific restriction assay, and DNA sequencing. In silico analysis was carried out to identify the impact of sequence variants on the protein structure. Chi-square (?? 2) test was used to compare the promoter methylation proportions of leiomyoma and myometrium tissues. No sequence variants were observed in exon 2 region, but three novel heterozygous germ line sequence variants, i.e., c.1010A?>?C, c.1021?G?>?A, and c.1066?T?>?C in exon 7 region of the FH gene were detected in 14/85 (16.5?%) of the cases examined. In silico analysis results showed that c.1010A?>?C and c.1021?G?>?A mutations damage the structure and function of FH, whereas c.1066?T?>?C mutation is mostly tolerant or neutral. No significant difference of FH promoter methylation status between the leiomyoma (11.76?%) and myometrium (5.88?%) tissues was observed (P?=?0.176). Therefore, it is concluded that somatic mutations in FH do not show pronounced effect in nonsyndromic uterine leiomyomas compared to that of their syndromic counterparts. However, higher frequency of FH mutations in leiomyoma cases raises the need to conduct larger number of prospective case-control and family-based studies to assess them as risk markers to nonsyndromic leiomyomas. 相似文献
999.
Ruth Minamisava Simonne S Nouer Otaliba L de Morais Neto Lícia Kamila Melo AnaLucia SS Andrade 《International journal of health geographics》2009,8(1):66
Background
Deaths due to homicides and traffic accidents among youth are a public health issue worldwide. Studies of the complex network of cause and effect on this topic point to both poverty and health inequalities. Different investigational approaches to intentional and unintentional deaths combined with socioeconomic variables can help create a better understanding of the association between violence and socioeconomic conditions. This study analyzed the spatial distribution and potential clusters of risk for intentional and unintentional deaths among youths aged 15-24 years in Goiania, a newly urbanized city in central Brazil. 相似文献1000.
Norliza Mohd. Noor Omar Mohd. Rijal Ashari Yunus S.A.R. Abu-Bakar 《Computerized medical imaging and graphics》2010,34(2):160-166
This paper presents a statistical method for the detection of lobar pneumonia when using digitized chest X-ray films. Each region of interest was represented by a vector of wavelet texture measures which is then multiplied by the orthogonal matrix Q2. The first two elements of the transformed vectors were shown to have a bivariate normal distribution. Misclassification probabilities were estimated using probability ellipsoids and discriminant functions. The result of this study recommends the detection of pneumonia by constructing probability ellipsoids or discriminant function using maximum energy and maximum column sum energy texture measures where misclassification probabilities were less than 0.15. 相似文献