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41.
Pennings RJ Te Brinke H Weston MD Claassen A Orten DJ Weekamp H Van Aarem A Huygen PL Deutman AF Hoefsloot LH Cremers FP Cremers CW Kimberling WJ Kremer H 《Human mutation》2004,24(2):185
Usher syndrome type II (USH2) is characterised by moderate to severe high-frequency hearing impairment, progressive visual loss due to retinitis pigmentosa and intact vestibular responses. Three loci are known for USH2, however, only the gene for USH2a (USH2A) has been identified. Mutation analysis of USH2A was performed in 70 Dutch USH2 families. Ten mutations in USH2A were detected, of which three are novel, c.949C>A, c.2242C>T (p.Gln748X) and c.4405C>T (p.Gln1468X). Including 9 previously published Dutch USH2a families, estimates of the prevalence of USH2a in the Dutch USH2 population were made. Mutations were identified in 62% of the families. In 28% both mutated alleles were identified, whereas in 34% the mutation in only one allele was found. It is estimated that about 28% of the Dutch USH2 families have a different causative gene. Analysis of deduced haplotypes suggests that c.1256G>T (p.Cys419Phe) is a Dutch ancestral mutation, occurring in 16% of the alleles. 相似文献
42.
The immunity of a combined DNA vaccine of HSV-2 glycoproteins B2 (gB2) and D2 (gD2) genes in comparison to individual vaccines was studied with regard to protecting against the HSV infection. Two recombinant DNA vaccines of the pHS2-gB2 or pHS2-gD2 were constructed and formulated. The neutralizing antibody titers appeared higher in the B2:D2 gene cocktail-vaccinated mice than that of the individual B2 or D2 gene-vaccinated group alone, and the positive KOS control induced higher titer of the neutralizing antibody than combined or individual gene vaccines. The mock-immunized mice failed to induce enough. The ranks for the CTL activity and the protection rates against the lethal intravaginal challenge were shown as KOS>B2:D2 cocktail>D2>B2 gene vaccines. The vaginal external diseases in the B2:D2 or D-vaccinated mice were significantly reduced against the challenging dosages. The virus titers in the vaginal secretions of the vaccinated mice significantly reduced with time, and the B2:D2 gene vaccine decreased more than each individual vaccine alone. It can be concluded that the cocktailed vaccines are more effective in the humoral and cellular immune responses in the mice, and in the protection of the mice against the intravaginal challenging dosages when compared with individual gene vaccines. All the DNA vaccines failed to block the latent infection in sensory nerves. 相似文献
43.
Predicting pregnancy and spermatogenesis by survival analysis during gonadotrophin treatment of gonadotrophin-deficient infertile men 总被引:4,自引:0,他引:4
Liu PY Gebski VJ Turner L Conway AJ Wishart SM Handelsman DJ 《Human reproduction (Oxford, England)》2002,17(3):625-633
BACKGROUND: Predictors of fertility or spermatogenesis during gonadotrophin therapy of gonadotrophin-deficient men remain poorly defined. METHODS AND RESULTS: In order to evaluate potential predictors, this study evaluated 29 consecutive gonadotrophin-deficient men all desiring paternity who received 43 courses of therapy in one centre between 1982 and 1998. The Kaplan-Meier survival analysis estimates of median (SE) time to a sperm concentration of >0, >5 and >20 x 10(6)/ml were 5.5 (1.1), 12.4 (2.3) and 29.1 (1.9) months respectively. Conception occurred in 22/43 cycles (with eight men achieving two pregnancies) with a median (SE) Kaplan-Meier estimate of 20.5 (4.7) months. The median sperm concentration at conception was 5.0 (SE 2.0; range 0.0-59.5) x 10(6)/ml. Multivariate correlated Cox proportional hazards models predicting these same sperm thresholds and conception were developed by forward stepwise variable selection with verification of the model by backward stepping. Larger testicular volume, prior gonadotrophin therapy, completion of puberty, older age, the absence of adverse fertility factors and the absence of multiple pituitary hormone deficiency predicted a favourable response. Multivariate modelling suggests that the two most important predictors of sperm output are testicular volume and pubertal status. The most important potentially modifiable predictor was prior gonadotrophin therapy. The efficacy of recombinant and urinary FSH were similar. Prior androgen therapy and partner's age did not appear to be significant. CONCLUSIONS: Since prolonged treatment may be required to induce spermatogenesis, attention to these predictors may allow appropriate early use of advanced reproductive technologies. 相似文献
44.
Association of MICA polymorphism with HLA-B51 and disease severity in Korean patients with Behcet's disease 总被引:1,自引:0,他引:1
Park SH Park KS Seo YI Min DJ Kim WU Kim TG Cho CS Mok JW Park KS Kim HY 《Journal of Korean medical science》2002,17(3):366-370
The HLA-B51 allele is known to be associated with Behcet's disease (BD) in many ethnic group. However, it has not yet been clarified whether the HLA-B51 gene itself is the pathogenic gene related to BD or whether it is some other gene in linkage disequlibrium with HLA-B51. Recently, the Triplet repeat (GCT/AGC) polymorphism in transmembrane region of the MHC class I chain-related A (MICA) gene was identified. To investigate the association of MICA with BD, we studied the MICA polymorphism in 108 Korean BD patients and 204 healthy controls in relation to the presence of HLA-B51 and clinical manifestations. The triplet repeat polymorphism was determined by polymerase chain reaction (PCR)-denaturing polyacrylamide gel electrophoresis (PAGE). The phenotype frequency of the MICA*A6 allele (relative risk, RR=2.15, p=0.002) and HLA-B51(RR=1.87, p=0.022) were significantly increased in the Korean patients with BD. A strong linkage disequilibrium was observed between the MICA*A6 and HLA-B51 in both the patients with BD and control subjects. Stratification analysis showed that MICA*A6 homozygosity was strongly associated with BD in the HLA-B51-negative population, and HLA-B51 was also associated with MICA*A6-negative population. In conclusion, MICA*A6 rather than HLA-B51 was strongly associated with Korean patients with BD, and the MICA*A6 allele is a useful susceptibility marker of BD, especially in the HLA-B5-negative 相似文献
45.
We studied the effect of low levels of vitamin B12 and folic acid, alone or combined, on cognitive performance in a population-based sample of 698 older adults (mean age = 68.7 years). No evidence was found for a vitamin-related memory deficit, but research participants with low levels of vitamin B12 exhibited reduced information processing speed relative to participants with normal vitamin B12 levels. 相似文献
46.
BACKGROUND: Young adults with early-onset major depressive disorder (MDD) may be at high risk of progression to bipolar disorder. Although hypomanic symptoms are common in young people with depression, many do not reach the strict DSM-IV and ICD-10 criteria for hypomania. We used an emerging innovative framework for bipolar spectrum to evaluate this question. METHODS: Consecutive referrals to a psychiatric outpatient clinic at a university health service were assessed for recurrent episodes of depression. DSM-IV diagnoses were based on a SCID-1 interview. We used two approaches to delineate bipolar spectrum. The first focused on bipolar spectrum disorder (BSD, as defined by Ghaemi et al. [Can. J. Psychiatry 47 (2002) 125]), and the second on a symptoms perspective based on MDD with a history of hypomanic symptoms, using a 15-point hypomanic symptoms checklist with a cut-off > or =8 or more symptoms (modified from J. Affect. Disord. 73 (2003) 39 and J. Affect. Disord. 73 (2003) 73). Data were also obtained on family history of affective disorder, course and number of episodes of depression, symptom severity, psychosocial functioning, suicidality and deliberate self-harm, and drug and alcohol use. RESULTS: High rates of bipolar and bipolar spectrum disorder were identified. Under DSM-IV, 14 subjects (16.1%) had bipolar affective disorder and 73 subjects (83.9%) had recurrent MDD. Depending on the method used to diagnose bipolar spectrum, between 47.1% and 77.0% of the total cohort could be so diagnosed. Hypomanic symptom counts, irrespective of duration, yielded the highest estimates for bipolar spectrum. High rates of pharmacological hypomania were also identified: 12 subjects (16.4%) with recurrent MDD group reported this, and all could be diagnosed with bipolar spectrum. LIMITATIONS: The reliability of using the 15-point hypomanic scale for the diagnostic assignments was not tested. All subjects were recruited from a university health service and, given the affluence of their parents, findings may not generalise to other populations. Most importantly, because bipolar family history and pharmacological hypomania were part of the diagnostic criteria of the BSD group, they could not be used as external validators for Ghaemi's BSD construct. CONCLUSIONS: Bipolar disorders emerge as extremely common in this cohort of young adults with recurrent depression. Antidepressant-induced hypomania and high scores on a hypomanic symptoms checklist help to identify patients who are likely to have a bipolar spectrum illness, but who do not meet DSM-IV criteria for bipolar disorder. This is a preliminary study, and further evidence from external validating strategies are needed to verify the bipolar status of these patients in a larger and unselected cohort representing a broader socio-economic demographic profile. 相似文献
47.
Daselaar SM Veltman DJ Rombouts SA Raaijmakers JG Jonker C 《Neurobiology of aging》2003,24(7):1005-1011
Age-related impairments in episodic memory have been related to a deficiency in semantic processing, based on the finding that elderly adults typically benefit less than young adults from deep, semantic as opposed to shallow, nonsemantic processing of study items. In the present study, we tested the hypothesis that elderly adults are not able to perform certain cognitive operations under deep processing conditions. We further hypothesised that this inability does not involve regions commonly associated with lexical/semantic retrieval processes, but rather involves a dysfunction of the medial temporal lobe (MTL) memory system. To this end, we used functional MRI on rather extensive groups of young and elderly adults to compare brain activity patterns obtained during a deep (living/nonliving) and a shallow (uppercase/lowercase) classification task. Common activity in relation to semantic classification was observed in regions that have been previously related to semantic retrieval, including mainly left-lateralised activity in the inferior prefrontal, middle temporal, and middle frontal/anterior cingulate gyrus. Although the young adults showed more activity in some of these areas, the finding of mainly overlapping activation patterns during semantic classification supports the idea that lexical/semantic retrieval processes are still intact in elderly adults. This received further support by the finding that both groups showed similar behavioural performances as well on the deep and shallow classification tasks. Importantly, though, the young revealed significantly more activity than the elderly adults in the left anterior hippocampus during deep relative to shallow classification. This finding is in line with the idea that age-related impairments in episodic encoding are, at least partly, due to an under-recruitment of the medial temporal lobe memory system. 相似文献
48.
Carlson DJ Stewart RD Li XA Jennings K Wang JZ Guerrero M 《Physics in medicine and biology》2004,49(19):4477-4491
Parallel in vitro and in vivo studies provide insight into the relationship between clinical response and intrinsic cellular radiosensitivity and may aid in the development of predictive assays. Compilations of radiosensitivity parameters from in vitro experiments can also be used to examine the potential effectiveness of alternative or new treatment plan designs until enough clinical data become available to directly estimate the requisite radiosensitivity parameters. In this work, survival data for six prostate cancer cell lines (ten datasets total) have been extracted from the literature and re-analysed using the linear-quadratic (LQ) survival model. The paired bootstrap technique for regression is used to compute 95% confidence intervals for the estimated radiosensitivity parameters. LQ radiosensitivity parameters derived from the in vitro data are then compared to radiosensitivity parameters derived from clinical data for prostate cancer. Estimates of alpha range from 0.09 to 0.35 Gy(-1) (all cell lines), and the alpha/beta ratio ranges from 1.09 to 6.29 Gy (all cell lines). Point estimates of the repair half-time (PPC-1, TSU-Pr1, PC-3 and DU-145 cell lines) range from 5.7 to 8.9 h (95% confidence interval from 0.26 h to 10.7 h). Differences in the radiosensitivity parameters determined from the data reported by different laboratories are as large as or larger than the differences in radiosensitivity parameters observed among the various prostate cell lines. The reported studies demonstrate that even seemingly small corrections for dose rate effects, such as those expected in high dose rate (HDR) experiments, can sometimes have a significant impact on estimates of alpha and alpha/beta. By neglecting dose rate effects in the analysis of HDR experiments, estimates of the alpha/beta, ratio may be too high by factors as large as 1.3 to 6.2. The half-time for repair derived from the in vitro experiments appears significantly larger (slower repair rate) than estimates derived from the clinical data. However, the prostate radiosensitivity parameters alpha and alpha/beta may be approximately the same in vitro and in vivo. Most of the in vitro data are consistent with an alpha/beta ratio for prostate cancer less than 3 or 4 Gy. 相似文献
49.
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