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991.
Two methods of whole-genome amplification enable accurate genotyping across a 2320-SNP linkage panel 总被引:6,自引:0,他引:6
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Barker DL Hansen MS Faruqi AF Giannola D Irsula OR Lasken RS Latterich M Makarov V Oliphant A Pinter JH Shen R Sleptsova I Ziehler W Lai E 《Genome research》2004,14(5):901-907
Comprehensive genome scans involving many thousands of SNP assays will require significant amounts of genomic DNA from each sample. We report two successful methods for amplifying whole-genomic DNA prior to SNP analysis, multiple displacement amplification, and OmniPlex technology. We determined the coverage of amplification by analyzing a SNP linkage marker set that contained 2320 SNP markers spread across the genome at an average distance of 2.5 cM. We observed a concordance of >99.8% in genotyping results from genomic DNA and amplified DNA, strongly indicating the ability of both methods used to amplify genomic DNA in a highly representative manner. Furthermore, we were able to achieve a SNP call rate of >98% in both genomic and amplified DNA. The combination of whole-genome amplification and comprehensive SNP linkage analysis offers new opportunities for genetic analysis in clinical trials, disease association studies, and archiving of DNA samples. 相似文献
992.
Physiological responses to intermittent and continuous exercise at the same relative intensity in older men 总被引:1,自引:0,他引:1
We investigated the physiological responses in older men to continuous (CEx) and intermittent (IEx) exercise. Nine men [70.4 (1.2) years, O2peak: 2.21 (0.20) l min–1; mean (SE)] completed eight exercise tests (two CEx and six IEx) on an electronically braked cycle ergometer in random order. CEx and IEx were performed at 50% and 70% O2peak. IEx was performed using 60sE:60sR, 30sE:30sR and 15sE:15sR exercise to rest ratios. The duration of exercise was adjusted so that the total amount of work completed was the same for each exercise test. Oxygen uptake (O2), minute ventilation (E) and heart rate (HR) were measured at the mid-point of each exercise test. Arterialised blood samples were obtained at rest and during exercise and analysed for pH and PCO2. At the same relative intensity (50% or 70% O2peak), IEx resulted in a significantly lower (P<0.01) O2, E and HR than CEx. There were no significant differences (P>0.05) in O2, E and HR measured at the mid point of the three exercise to rest ratios at 50% and 70% O2peak. pH and PCO2 during CEx and IEx at 50% O2peak were not significantly different from rest. CEx performed at 70% O2peak resulted in significant decreases (P<0.05) in pH and PCO2. There was a significant decrease (P<0.05) in pH only during the 60sE:60sR IEx at 70% O2peak. Changes in arterialised PCO2 during the 60sE:60sR, 30sE:30sR and 15sE:15sR at both 50% and 70% O2peak exercise tests were not significant. When exercising at the same percentage of O2peak and with the total amount of work fixed, IEx results in significantly lower physiological responses than CEx in older men. All results are given as mean (SE). 相似文献
993.
Elizabeth Dormandy Martin C Gulliford Erin P Reid Katrina Brown Theresa M Marteau 《The British journal of general practice》2008,58(548):154-159
BACKGROUND: Antenatal sickle cell and thalassaemia screening sometimes occurs too late to allow couples a choice regarding termination of affected fetuses. The target gestational age for offering the test in the UK is 10 weeks. AIM: To describe the proportion of women screened before 70 days' (10 weeks') gestation and the delay between pregnancy confirmation in primary care and antenatal sickle cell and thalassaemia screening. DESIGN OF STUDY: Cohort study of reported pregnancies. SETTING: Twenty-five general practices in two UK inner-city primary care trusts offering universal screening. METHOD: Anonymised data on all pregnancies reported to participating general practices was collected for a minimum of 6 months. RESULTS: There were 1441 eligible women intending to proceed with their pregnancies, whose carrier status was not known. The median (interquartile range [IQR]) gestational age at pregnancy confirmation was 7.6 weeks (6.0-10.7 weeks) and 74% presented before 10 weeks. The median gestational age at screening was 15.3 weeks (IQR = 12.6-18.0 weeks), with only 4.4% being screened before 10 weeks. The median delay between pregnancy confirmation and screening was 6.9 weeks (4.7-9.3 weeks) After allowing for practice level variation, there was no association between delay times and maternal age, parity, and ethnic group. CONCLUSION: About 74% of women consulted for pregnancy before 10 weeks' gestation but fewer than 5% of women were screened before the target time of 10 weeks. Reducing the considerable delay between pregnancy confirmation in primary care and antenatal sickle cell and thalassaemia screening requires methods of organising and delivering antenatal care that facilitate earlier screening to be developed and evaluated. 相似文献
994.
Woodward MJ Best A Sprigings KA Pearson GR Skuse AM Wales A Hayes CM Roe JM Low JC La Ragione RM 《International journal of medical microbiology : IJMM》2003,293(4):299-308
Ruminants are regarded as a primary reservoir for Escherichia coli O157:H7, an important human pathogen. Intimin, encoded by the Locus of Enterocyte Effacement by E. coli O157:H7 organisms, has been cited as one bacterial mechanism of colonisation of the gastrointestinal tract. To confirm this and to test whether a non-toxigenic E. coli O157:H7 strain would colonise and persist in a sheep model, E. coli O157:H7 strain NCTC12900, that lacks Shiga toxin (stx) genes, was evaluated for use in a sheep model of persistence. Following oral inoculation of six-week-old sheep, persistent excretion of NCTC12900 was observed for up to 48 days. E. coli O157-associated attaching-effacing (AE) lesions were detected in the caecum and rectum of one six-week-old lamb, one day after inoculation. This is the first recorded observation of AE lesions in orally inoculated weaned sheep. Also, mean faecal excretion scores of NCTC12900 and an isogenic intimin (eae)-deficient mutant were determined from twenty-four six-week-old orally inoculated sheep. The eae mutant was cleared within 20 days and had lower mean excretion scores at all time points after day one post inoculation compared with the parental strain that was still being excreted at 48 days. Tissues were collected post mortem from animals selected at random from the study groups over the time course of the experiment. The eae mutant was detected in only 1/43 samples but the parental strain was recovered from 64/140 samples primarily from the large bowel although rumen, duodenum, jejunum, and ileum were culture positive especially from animals that were still excreting at and beyond 27 days after inoculation. 相似文献
995.
Antisense oligonucleotides offer great therapeutic potential provided adequate intracellular penetration can be achieved. In this study, we evaluated the effectiveness of microencapsulating antisense oligonucleotides to tumor necrosis factor (TNF) in suppressing TNF release in vitro and in vivo. Microencapsulation of TNF oligomers was performed using albumin to produce microcapsules 0.6-1.0 mum in size that target phagocytic cells. Albumin microcapsules containing fluoresceinated TNF oligomers were incubated with U-937 cells to observe uptake. Microcapsules were added to whole blood and stimulated with Escherichia coli endotoxin. Endotoxin was given intravenously (i.v.) to rats along with 100 mug microencapsulated TNF oligomers to determine TNF inhibition and animal survival. E. coli was given intraperitoneally (i.p.) along with gentamicin and microencapsulated TNF oligomers to assess TNF inhibition and animal survival. The duration of microencapsulated antisense TNF oligomers was also determined in vivo. The results demonstrated rapid uptake of the microcapsules by macrophages after 2 h and 4 h incubation. There was improvement in TNF inhibition in vitro and improved animal survival by microencapsulated antisense in both endotoxin (100% survival) and peritonitis models (70% survival) compared with free antisense oligomers in solution. Microencapsulation extended the duration of action of the oligomers to 72 h. Intracellular targeting of macrophages with antisense oligomers to TNF by microencapsules as a delivery system improves TNF inhibition using the models of whole blood endotoxin stimulation and endotoxic shock and peritonitis in rats. 相似文献
996.
Martin DM Mindell MH Kwierant CA Glover TW Gorski JL 《American journal of medical genetics. Part A》2003,(3):268-271
Complex congenital heart defects (CHD) are associated with a variety of single gene abnormalities and chromosomal rearrangements. Of the various forms of CHD, aortic arch interruption, a conotruncal heart defect, is relatively uncommon. Here we report a male neonate with aortic arch interruption type B, secundum atrial septal defect, perimembranous ventricular septal defect, patent ductus arteriosus, aortic and subaortic stenosis, and trisomy 5q31.1q35.1 resulting from a maternal balanced insertion (20;5). Chromosomal deletions, including deletion 22q11, have been reported with interrupted aortic arch (IAA); however, to our knowledge this is the first report of a trisomy of distal chromosome 5q associated with aortic arch interruption. Here we compare this child's features to other cases of trisomy 5q31.1q35.1, and review other causes of IAA. We conclude that gene dosage in this chromosomal region likely influences aortic arch development. 相似文献
997.
The external shape and thickness of the enamel component of primate molars have been employed extensively in phylogenetic studies of primate relationships. The dentine component of the molar crown also has been suggested to be indicative of phylogenetic relationships, but few studies have quantified dentine morphology in order to evaluate this possibility. To explore the utility of dentine shape as an indicator of phylogenetic affinity, a two-dimensional geometric morphometric analysis (EDMA-II) was performed using nine homologous land-marks on a sample of sectioned maxillary molars of extant ceboid, cercopithecoid, and hominoid primates. Results indicate that dentine shape (the configuration of the enamel-dentine junction, or EDJ) can distinguish taxa at every taxonomic level examined, including superfamilies, subfamilies, and closely related genera and species. This supports the idea that dentine morphology may be useful for phylogenetic studies. It is further suggested that the morphology of the EDJ may be more conservative than enamel morphology, and perhaps better-suited to phylogenetic studies. Among the samples studied, cercopithecoid primates have a unique dentine shape, and it is suggested that the development of bilophodont molars may be related to the distinctive EDJ configuration in cercopithecoids. 相似文献
998.
Quantitative gene expression analysis reveals transition of fetal liver progenitor cells to mature hepatocytes after transplantation in uPA/RAG-2 mice 总被引:14,自引:0,他引:14
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999.
Cellular localisation of HHV-8 in Castleman's disease: is there a link with lymph node vascularity? 总被引:4,自引:0,他引:4
J O'Leary M Kennedy D Howells I Silva V Uhlmann K Luttich S Biddolph S Lucas J Russell N Bermingham M O'Donovan M Ring C Kenny M Sweeney O Sheils C Martin S Picton K Gatter 《Molecular pathology》2000,53(2):69-76
AIMS: Human herpesvirus 8 (HHV-8) has been identified in multicentric Castleman's disease and in angioimmunoblastic lymphadenopathies. However, the presence of the virus does not necessarily indicate an aetiological role in these conditions. This study investigates the cell types infected by HHV-8 in Castleman's disease and examines the correlation between HHV-8 and Castleman's disease lymph node angiogenesis. METHODS: Sixteen formalin fixed, paraffin wax embedded samples from patients with Castleman's disease (six multicentric, 10 solitary) were examined for the presence of HHV-8 using the polymerase chain reaction (PCR), non-isotopic in situ hybridisation, PCR in situ hybridisation (PCR-ISH), and real time quantitative TaqMan PCR to HHV-8 open reading frame 26 (ORF-26), and viral (v)-cyclin encoding regions. Vascularity was assessed using CD34, CD31, and factor VIII immunocytochemistry, and lymph nodes were scored as "low" or "high". RESULTS: Five multicentric Castleman's disease and two solitary Castleman's disease biopsies were positive for HHV-8. HHV-8 was identified in approximately 10% of intranodal B lymphocytes, in endothelial cells, and in subcapsular spindle cell proliferations. The copy number of HHV-8 was low at 10-50 copies/1000 cells. The highest copy number was in subcapsular spindle cells. There was no correlation between vascularity score and HHV-8 status. CONCLUSION: The preferential localisation of HHV-8 in subcapsular spindle cell proliferations (where early intranodal Kaposi's sarcoma initiates) and endothelial cells in Castleman's disease might finally explain the link between intranodal Kaposi's sarcoma and Castleman's disease. 相似文献
1000.
Oral ganciclovir for patients with cytomegalovirus retinitis treated with a ganciclovir implant. Roche Ganciclovir Study Group 总被引:9,自引:0,他引:9
Martin DF Kuppermann BD Wolitz RA Palestine AG Li H Robinson CA 《The New England journal of medicine》1999,340(14):1063-1070
BACKGROUND: The intraocular ganciclovir implant is effective for local treatment of cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome (AIDS), but it does not treat or prevent other systemic manifestations of cytomegalovirus infection. METHODS: Three hundred seventy-seven patients with AIDS and unilateral cytomegalovirus retinitis were randomly assigned to one of three treatments: a ganciclovir implant plus oral ganciclovir (4.5 g daily), a ganciclovir implant plus oral placebo, or intravenous ganciclovir alone. The primary outcome measure was the development of new cytomegalovirus disease, either contralateral retinitis or biopsy-proved extraocular disease. RESULTS: The incidence of new cytomegalovirus disease at six months was 44.3 percent in the group assigned to the ganciclovir implant plus placebo, as compared with 24.3 percent in the group assigned to the ganciclovir implant plus oral ganciclovir (P=0.002) and 19.6 percent in the group assigned to intravenous ganciclovir alone (P<0.001). As compared with placebo, oral ganciclovir reduced the overall risk of new cytomegalovirus disease by 37.6 percent over the one-year period of the study (P=0.02). However, in the subgroup of 103 patients who took protease inhibitors, the rates of new cytomegalovirus disease were low and of similar magnitude, regardless of treatment assignment. Progression of retinitis in the eye that initially received an implant was delayed by the addition of oral ganciclovir, as compared with placebo (P=0.03). Treatment with oral or intravenous ganciclovir reduced the risk of Kaposi's sarcoma by 75 percent (P=0.008) and 93 percent (P<0.001), respectively, as compared with placebo. CONCLUSIONS: In patients with AIDS and cytomegalovirus retinitis, oral ganciclovir in conjunction with a ganciclovir implant reduces the incidence of new cytomegalovirus disease and delays progression of the retinitis. Treatment with oral or intravenous ganciclovir also reduces the risk of Kaposi's sarcoma. 相似文献