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101.
102.
A region on chromosome 17 has recently been highlighted as linked to autism (MIM[209850]) in multiple studies and evidence has accumulated suggesting that male-only families (those families that have produced only affected males) provide the major contribution to linkage at this locus. In an attempt to comprehensively test for association of common variants to autism within the region on chromosome 17 defined in Stone et al. (Stone, J.L., Merriman, B., Cantor, R.M., Yonan, A.L., Gilliam, T.C., Geschwind, D.H. and Nelson, S.F. (2004) Evidence for sex-specific risk alleles in autism spectrum disorder. Am. J. Hum. Genet., 75, 1117-1123), a dense panel of single nucleotide polymorphisms (SNPs) was selected across the linkage peak and analyzed in a trio-based study design. SNPs were genotyped in 219 independent trios at an average intermarker distance of 6.1 kb across the 13.7 Mb interval. This provided ~80% coverage of common HapMap variation present in Caucasians, testing exonic, intronic, promoter and intergenic regions, as knowledge of important functional regions within the genome is currently limited. In this comprehensive association study of a linkage region in autism, no single SNP or haplotype association was sufficient to account for the initial linkage signal. Nominally significant single SNP and/or haplotype-based association results were detected in 15 genes, of which, MYO1D, ACCN1 and LASP1 stand out as genes with autism risk alleles requiring further study, with potential GRRs in the range of 1.34-2.29. 相似文献
103.
H Merriman 《The Practitioner》1983,227(1379):819-825
This study of attitudes toward contraception among women seeking abortion involved consecutive patients seen at intervals over a 10-month period. 253 women with an age range of 14-47 years were interviewed. Medical contraindications to use of the combined oral contraceptive (OC) pill were reported by 32 women (12.6%). In 17 cases the woman, not her doctor, had decided to stop OC use. The IUD was contraindicated in 8 women (3.2%). The women who used no contraception included a few who relied on the safe period or withdrawal. In those aged 19 or younger, 56 (57%) used no method at the time of conception and 39 of these had never used any contraceptive method. Sheath failure was said to have occurred in 80 conceptions (31.6%), and 15 women (5.9%) fitted with an IUD conceived. 32 women (12.6%) conceived while taking the combined OC. 27 of these women were aware that they had forgotten to take 1 or more of their pills. 2 women were prescribed antibiotics and were not advised to use other precautions. 2 women were taking a 20 mg estrogen pill, and it was only in these 2 that any method failure could be identified. All but 5 of the 133 women who selected the combined pill were under age 30. Tubal ligation was chosen by 14 of the 31 women aged 35 or older. Sources of information on contraception and associated fears were recorded, and women in whom either the pill or the IUD was contraindicated are excluded. In younger women the doctor was used less as a source of information than friends or books but more than school, boyfriend, or husband. The doctor was used more by women aged 30 or older. The number of women with "fears" was sizeable. 55.7% of those aged 19 or under lacked useful maternal advice. 28 said they had problems in obtaining contraceptive supplies and advice. There were 12 young women aged 14 or 15, 8 of whom had not sought contraceptive advice since they did not have boyfriends and their sexual encounters were isolated and unpremeditated. The advice reported to have been given by some doctors seems to have been inappropriate. All the women aged 30 years or older not needing contraception had undergone tubal ligation. The interviews were found to be helpful to many patients. Some found it useful to have an impartial listener at a time of emotional stress. Others found more positive help in clarifying their ideas and correcting misbeliefs. Planning for the future was considered particularly helpful. 相似文献
104.
TM Sankary ; G Yang ; JM Romeo ; PP Ulrich ; MP Busch ; BD Rawal ; GN Vyas 《Transfusion》1994,34(8):656-660
BACKGROUND: Since screening for antibody to hepatitis C virus (HCV) was introduced in 1990, posttransfusion hepatitis has been reduced to nearly background levels. This has led to reconsideration of the value of testing donated blood for elevated alanine aminotransferase (ALT). The contribution of ALT testing in detecting seronegative infection was evaluated by the performance of polymerase chain reaction (PCR) for hepatitis B virus (HBV) or HCV in plasma from ALT-elevated blood units. STUDY DESIGN AND METHODS: Testing was performed on 375 units of plasma, derived from an equivalent of 47,500 blood donations, with a highly sensitive hemi-nested PCR procedure. Using a triplet of primers directed at the conserved regions of HBV DNA and 5'-noncoding regions of HCV RNA, the hemi-nested PCR assay can reliably amplify 10 viral molecules to levels detectable in ethidium bromide-stained agarose gels. Pools of plasma from groups of four donors were screened with hemi-nested PCR. For any reactive pools, the plasma from individual donors was retested twice on different aliquots. RESULTS: Two of 375 units, both with midrange ALT elevation, were repeatedly reactive in hemi-nested PCR (one each for HBV DNA and HCV RNA). However, samples from the two suspect donors tested 9 and 5 months later revealed no seroconversion, elevated ALT, or viral genomes in hemi-nested PCR. CONCLUSION: The lack of confirmed HBV or HCV infection in this study representing an estimated 47,500 voluntary blood donations suggests that routine ALT testing for further prevention of posttransfusion hepatitis after exclusion of HBV- and/or HCV-seropositive blood may be superfluous. 相似文献
105.
106.
Mepacrine uptake into platelets and bone marrow megakaryocytes was analyzed to further characterize the dense granule defects in a group of seven mouse pigment mutants that have characteristics of platelet storage pool disease (SPD). In contrast to our previous studies using electron microscopy, this method revealed that all mutants had normal numbers of dense granules. However, total mepacrine uptake in all mutant platelets was significantly diminished to less than 50% of normal uptake. Also, the flashing phenomenon observed when normal dense granules are irradiated with ultraviolet light was either greatly diminished or absent when platelets of individual mutants were similarly irradiated. Therefore the principal defect in the mutant platelets is an inability to accumulate dense granule contents rather than an absence of the granules. Mepacrine uptake into megakaryocytes was indistinguishable in normal and mutant mice. This indicates the mutant dense granule defects appear either very late in megakaryocyte development or early in platelet formation in correlation with development of the mature dense granule. By standard transmission electron microscopy we have not been able to detect gross structural or subcellular abnormalities in either platelets or megakaryocytes of mutant mice. It appears all seven mutants produce immature or functionally abnormal dense granules. 相似文献
107.
Pullen DJ; Sullivan MP; Falletta JM; Boyett JM; Humphrey GB; Starling KA; Land VJ; Dyment PG; Vats T; Duncan MH 《Blood》1982,60(5):1159-1168
In an attempt to improve the poor outlook for children with T-cell leukemia (T-ALL), the Southwest Oncology Group, Pediatric Division, used a modified LSA2-L2 multidrug regimen to treat 53 patients with E- rosette-positive T-ALL. This regimen was chosen because of its demonstrated efficacy in T-cell (mediastinal) non-Hodgkin's lymphoma. Complete remission (CR) rate was 88%. Range of follow-up for those patients remaining in CR is 24-49 mo (median 39 mo). Life table analysis estimates that 40% (SE 8.3%) of all patients who started induction therapy will remain failure-free at 3 yr. For patients achieving CR, 46% (SE 9%) are projected to remain in both marrow and extramedullary CR at 3 yr. Median failure-free duration was 13 mo, but only 1 patient has relapsed beyond 16 mo. Twenty-nine percent of initial relapses were isolated CNS relapses. The following presenting factors did not relate significantly to outcome: hemoglobin, platelet count, uric acid, race, and mediastinal mass. Age greater than 10 yr was a poor prognosis indicator only in the less than 50,000/microliter WBC group. Sex was not a significant factor after adjusting for WBC. WBC was the most important prognostic factor: 19% (SE 8%) of patients with WBC greater than 50,000/microliter are projected to remain failure- free at 3 yr as compared to 67% (SE 11%) of patients with WBC less than 50,000/microliter. Although the overall results are better than those previously reported for pediatric patients with T-ALL, the long-term failure-free rate remains low for patients presenting with greater than 50,000/microliter WBC. 相似文献
108.
The exact pathophysiology of varicocele and the subsequent alteration of spermatogenesis has been the subject of much debate. Despite an enormous amount of literature on the subject, the appropriate management of varicocele in the adolescent patient population has not yet been clearly elucidated. While not every male with varicocele will be subfertile, the possibility potentially lends credence to early diagnosis for those in whom treatment will have an impact. 相似文献
109.
110.
Spaulding AR Lin YC Merriman JA Brosnahan AJ Peterson ML Schlievert PM 《Vaccine》2012,30(34):5099-5109
Staphylococcus aureus causes significant illnesses throughout the world, including toxic shock syndrome (TSS), pneumonia, and infective endocarditis. Major contributors to S. aureus illnesses are secreted virulence factors it produces, including superantigens and cytolysins. This study investigates the use of superantigens and cytolysins as staphylococcal vaccine candidates. Importantly, 20% of humans and 50% of rabbits in our TSS model cannot generate antibody responses to native superantigens. We generated three TSST-1 mutants; G31S/S32P, H135A, and Q136A. All rabbits administered these TSST-1 toxoids generated strong antibody responses (titers>10,000) that neutralized native TSST-1 in TSS models, both in vitro and in vivo. These TSST-1 mutants lacked detectable residual toxicity. Additionally, the TSST-1 mutants exhibited intrinsic adjuvant activity, increasing antibody responses to a second staphylococcal antigen (β-toxin). This effect may be due to TSST-1 mutants binding to the immune co-stimulatory molecule CD40. The superantigens TSST-1 and SEC and the cytolysin α-toxin are known to contribute to staphylococcal pneumonia. Immunization of rabbits against these secreted toxins provided complete protection from highly lethal challenge with a USA200 S. aureus strain producing all three exotoxins; USA200 strains are common causes of staphylococcal infections. The same three exotoxins plus the cytolysins β-toxin and γ-toxin contribute to infective endocarditis and sepsis caused by USA200 strains. Immunization against these five exotoxins protected rabbits from infective endocarditis and lethal sepsis. These data suggest that immunization against toxoid proteins of S. aureus exotoxins protects from serious illnesses, and concurrently superantigen toxoid mutants provide endogenous adjuvant activity. 相似文献