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41.
Lovering Ruth; Middleton-Price Helen R.; O'Reilly Marie-Anne J.; Genet Sally A.; Parkar Mohammed; Sweatman Angela K.; Bradley Linda D.; Alterman Lesley A.; Malcolm Sue; Morgan Gareth; Levinsky Roland J.; Kinnon Christine 《Human molecular genetics》1993,2(2):139-141
Genetic linkage analysis has been instrumental in mapping thegene for X-linked agammaglobulinemia (XLA) to the proximal longarm of the human X chromosome, to Xq22. Due to the relativerarity of this disease the localization of the gene within Xq22has remained imprecise. We have investigated twenty-nine familiesaffected by XLA and have found no recombinants with the DXS178locus in over 30 informative meioses. DXS178 is now the mostreliable and informative locus for use in pre-natal diagnosisand carrier detection of XLA. In addition, we have identifiednew closely linked proximal and distal flanking markers forXLA, DXS442 and DXS101, respectively. These loci are separatedby 2cM, considerably reducing the extent of DNA within whichthe XLA locus can be contained. This will open up the way formore directed positional cloning efforts for the isolation ofthe XLA gene. 相似文献
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Transgenic rat model of Huntington's disease 总被引:12,自引:0,他引:12
von Hörsten S Schmitt I Nguyen HP Holzmann C Schmidt T Walther T Bader M Pabst R Kobbe P Krotova J Stiller D Kask A Vaarmann A Rathke-Hartlieb S Schulz JB Grasshoff U Bauer I Vieira-Saecker AM Paul M Jones L Lindenberg KS Landwehrmeyer B Bauer A Li XJ Riess O 《Human molecular genetics》2003,12(6):617-624
Huntington's disease (HD) is a late manifesting neurodegenerative disorder in humans caused by an expansion of a CAG trinucleotide repeat of more than 39 units in a gene of unknown function. Several mouse models have been reported which show rapid progression of a phenotype leading to death within 3-5 months (transgenic models) resembling the rare juvenile course of HD (Westphal variant) or which do not present with any symptoms (knock-in mice). Owing to the small size of the brain, mice are not suitable for repetitive in vivo imaging studies. Also, rapid progression of the disease in the transgenic models limits their usefulness for neurotransplantation. We therefore generated a rat model transgenic of HD, which carries a truncated huntingtin cDNA fragment with 51 CAG repeats under control of the native rat huntingtin promoter. This is the first transgenic rat model of a neurodegenerative disorder of the brain. These rats exhibit adult-onset neurological phenotypes with reduced anxiety, cognitive impairments, and slowly progressive motor dysfunction as well as typical histopathological alterations in the form of neuronal nuclear inclusions in the brain. As in HD patients, in vivo imaging demonstrates striatal shrinkage in magnetic resonance images and a reduced brain glucose metabolism in high-resolution fluor-deoxy-glucose positron emission tomography studies. This model allows longitudinal in vivo imaging studies and is therefore ideally suited for the evaluation of novel therapeutic approaches such as neurotransplantation. 相似文献
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Stress, coping, and hepatitis B antibody status 总被引:4,自引:0,他引:4
OBJECTIVE: The present study investigated the association between exposure to stressful life events, coping style, and antibody status after hepatitis B vaccination. METHODS: Two hundred sixty medical school undergraduates, who had received the three-dose hepatitis B vaccine before recruitment to this study, completed questionnaires measuring exposure to stressful life events during the past year, customary coping strategies, and health behaviors. Antibodies against hepatitis B surface antigen were determined; levels <100 mIU/ml were deemed inadequate. RESULTS: Two participant cohorts were identified: those vaccinated within the last year and those vaccinated earlier. In the early vaccination cohort, participants with greater-than-average stress exposures had a more than two-fold increased risk of having an inadequate antibody titer. Coping by accepting the reality of stressful situations proved protective, whereas coping by substance use increased the risk of having an inadequate antibody count in this cohort. These associations remained significant after adjustment for possible mediators. Furthermore, the effects of stress and coping were largely independent of one another. Neither stress nor coping was significantly associated with antibody status in the recently vaccinated cohort. CONCLUSIONS: The present study confirms that the immune system is sensitive to variations in psychological factors. Stressful life events and coping strategy seem to have a continuing impact on hepatitis B antibody status. 相似文献
45.
Joanne Young Barbara Leggett Corinne Gustafson Michael Ward Jeffrey Searle Lesley Thomas Ron Buttenshaw Georgia Chenevix-Trench 《Human mutation》1993,2(5):351-354
Genomic instability, as demonstrated by the presence of additional alleles at short tandemly repeated (STR) loci, has recently been observed in colorectal tumours from individuals with hereditary non-polyposis colorectal cancer (HNPCC), and in some sporadic tumours. These neoplasms have been called replication error positive (RER+). In this study, we confirm the presence of genomic instability in a proportion of unselected colorectal carcinomas but find no evidence of instability in adenomas. We further report replication errors in a tetranucleotide sequence, and in STRs within two tumour suppressor genes. 108 colorectal adenocarcinomas and 46 adenomas were analysed for the presence of variant bands at 4–15 microsatellite markers. Seven (6.5%) of carcinomas were RER+, four of which originated from the proximal colon. Analysis of the adenomas and of matched adenoma-carcinoma and carcinoma-metastatic samples from four patients suggests that the replication errors may occur during the development of carcinomas but are rare in adenomas. © 1993 Wiley-Liss, Inc. 相似文献
46.
CSnrc, a new user-code for the EGSnrc Monte Carlo system is described. This user-code improves the efficiency when calculating ratios of doses from similar geometries. It uses a correlated sampling variance reduction technique. CSnrc is developed from an existing EGSnrc user-code CAVRZnrc and improves upon the correlated sampling algorithm used in an earlier version of the code written for the EGS4 Monte Carlo system. Improvements over the EGS4 version of the algorithm avoid repetition of sections of particle tracks. The new code includes a rectangular phantom geometry not available in other EGSnrc cylindrical codes. Comparison to CAVRZnrc shows gains in efficiency of up to a factor of 64 for a variety of test geometries when computing the ratio of doses to the cavity for two geometries. CSnrc is well suited to in-phantom calculations and is used to calculate the central electrode correction factor Pcel in high-energy photon and electron beams. Current dosimetry protocols base the value of Pcel on earlier Monte Carlo calculations. The current CSnrc calculations achieve 0.02% statistical uncertainties on Pcel, much lower than those previously published. The current values of Pcel compare well with the values used in dosimetry protocols for photon beams. For electrons beams, CSnrc calculations are reported at the reference depth used in recent protocols and show up to a 0.2% correction for a graphite electrode, a correction currently ignored by dosimetry protocols. The calculations show that for a 1 mm diameter aluminum central electrode, the correction factor differs somewhat from the values used in both the IAEA TRS-398 code of practice and the AAPM's TG-51 protocol. 相似文献
47.
Pui Fung Li Mark A. McEvoy Sharmaine McKiernan Peter W. Schofield Lesley K. MacDonald-Wicks Amanda J. Patterson 《Nutrients》2021,13(3)
There is a lack of evidence to determine if diet quality is associated with cognitive performance in older adults. Therefore, the aim of this study was to examine whether diet quality is associated with cognitive performance among older adults. A cross-sectional, secondary analysis of baseline data from the Hunter Community Study (HCS), comparing diet quality, measured using the Australian Recommended Food Score (ARFS), along with validated cognitive performance instruments the Audio Recorded Cognitive Screen (ARCS) and the Mini-Mental State Examination (MMSE) were undertaken in adults aged 55–85 years, living in Newcastle, NSW, Australia. Adjusted linear regression analyses showed that, compared with the lowest ARFS quintile, those in the highest quintile had an ARCS score 5.883 units greater (p < 0.001; R2 = 0.0098). Furthermore, when quintiles of ARFS score were tested against each ARCS sub-scale score, statistically significant associations were observed with the greatest effect for the Memory (β = 4.055; p = 0.001; R2 = 0.0065) and Attention (β = 4.136; p = 0.002; R2 = 0.0047) domains. No statistically significant associations were observed between quintiles of ARFS and MMSE score in the adjusted linear regression analyses. In conclusion, a positive association was observed between diet quality and cognitive performance within this sample of older Australian adults. Further investigation of the above association over time, when follow-up data becomes available, in longitudinal analysis is recommended. 相似文献
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Carmen H Logie Moses Okumu Daniel Kibuuka Musoke Robert Hakiza Simon Mwima Peter Kyambadde Heather Abela Lesley Gittings Joshua Musinguzi Lawrence Mbuagbaw Stefan Baral 《Journal of the International AIDS Society》2021,24(3)
IntroductionHIV‐related risks may be exacerbated in humanitarian contexts. Uganda hosts 1.3 million refugees, of which 60% are aged under 18. There are knowledge gaps regarding HIV testing facilitators and barriers, including HIV and intersecting stigmas, among urban refugee youth. In response, we explored experiences and perspectives towards HIV testing strategies, including HIV self‐testing, with urban refugee youth in Kampala, Uganda.MethodsWe implemented a qualitative study with refugee cisgender youth aged 16 to 24 living in Kampala''s informal settlements from February‐April 2019. We conducted five focus groups with refugee youth, including two with adolescent boys and young men, two with adolescent girls and young women and one with female sex workers. We also conducted five key informant (KI) interviews with government, non‐government and community refugee agencies and HIV service providers. We conducted thematic analyses to understand HIV testing experiences, perspectives and recommendations.ResultsParticipants (n = 49) included young men (n = 17) and young women (n = 27) originally from the Democratic Republic of Congo [DRC] (n = 29), Rwanda (n = 11), Burundi (n = 3) and Sudan (n = 1), in addition to five KI (gender: n = 3 women, n = 2 men; country of origin: n = 2 Rwanda, n = 2 Uganda, n = 1 DRC). Participant narratives revealed stigma drivers included fear of HIV infection; misinformation that HIV is a “Ugandan disease”; and blame and shame for sexual activity. Stigma facilitators included legal precarity regarding sex work, same‐sex practices and immigration status, alongside healthcare mistreatment and confidentiality concerns. Stigma experiences were attributed to the social devaluation of intersecting identities (sex work, youth, refugees, sexual minorities, people living with HIV, women). Participants expressed high interest in HIV self‐testing. They recommended HIV self‐testing implementation strategies to be peer supported and expressed concerns regarding sexual‐ and gender‐based violence with partner testing.ConclusionsIntersecting stigma rooted in fear, misinformation, blame and shame, legal precarity and healthcare mistreatment constrain current HIV testing strategies with urban refugee youth. Findings align with the Health Stigma and Discrimination Framework that conceptualizes stigma drivers and facilitators that devalue intersecting health conditions and social identities. Findings can inform multi‐level strategies to foster enabling HIV testing environments with urban refugee youth, including tackling intersecting stigma and leveraging refugee youth peer support. 相似文献