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21.
Use of Pulsed-Field Gel Electrophoresis for Molecular Epidemiologic and Population Genetic Studies of Mycobacterium tuberculosis 总被引:3,自引:0,他引:3 下载免费PDF全文
Samir P. Singh Hugh Salamon Carol J. Lahti Mehran Farid-Moyer Peter M. Small 《Journal of clinical microbiology》1999,37(6):1927-1931
Pulsed-field gel electrophoresis (PFGE) is a powerful molecular biology technique which has provided important insights into the epidemiology and population biology of many pathogens. However, few studies have used PFGE for the molecular epidemiology of Mycobacterium tuberculosis. A laboratory protocol was developed to determine the typeability, stability, and reproducibility of PFGE typing of M. tuberculosis. Formal data-analytical techniques were used to assess the genetic diversity elucidated by PFGE analyses using four separate restriction enzymes and by IS6110 RFLP analyses, as well as to assess the concordance among these typing methods. One hundred epidemiologically characterized clinical isolates of M. tuberculosis were genotyped with four different PFGE enzymes (AseI, DraI, SpeI, and XbaI), as well as by RFLP analysis with IS6110. Identical patterns were found among 34 isolates known to be genetically related, suggesting that the PFGE protocol is robust and reproducible. Among 66 isolates representing population-sampled cases, heterozygosity and information content dependency estimates indicate that all five genotyping systems capture quantitatively similar levels of genetic diversity. Nevertheless, comparisons between PFGE analyses and IS6110 typing reveals that PFGE provided more discrimination among isolates with fewer than five copies of IS6110 and less clustering in isolates with five or more copies. The comparisons confirm the hypothesis that the resolution of IS6110 RFLP genotyping is dependent upon the number of IS6110 elements in the genome of isolates. The general concordance among the results obtained with four independent enzymes suggests that M. tuberculosis is a clonal organism. The availability of a robust genotyping technique largely independent of repetitive elements has implications for the molecular epidemiology of M. tuberculosis. 相似文献
22.
Copy number alterations and neoplasia‐specific mutations in MELK,PDCD1LG2, TLN1, and PAX5 at 9p in different neoplasias 下载免费PDF全文
Virinder Kaur Sarhadi Leo Lahti Ilari Scheinin Pekka Ellonen Eeva Kettunen Massimo Serra Katia Scotlandi Piero Picci Sakari Knuutila 《Genes, chromosomes & cancer》2014,53(7):579-588
Genetic alterations affecting 9p are commonly present in many cancer types and many cancer‐related genes are located in this chromosomal region. We sequenced all of the genes located in a 32Mb region of 9p by targeted next generation sequencing (NGS) in 96 patients with different cancer types, including acute lymphoblastic leukemia, bone malignant fibrous histiocytoma/undifferentiated pleomorphic sarcoma, fibrosarcoma, Ewing's sarcoma, and lung carcinoma. Copy number alterations (CNA), and mutations were studied from the NGS data. We detected a deletion at the CDKN2A locus as being the most frequent genetic alteration in all cancer types. In addition to this locus, NGS also identified other small regions of copy number loss and gain. However, different cancer types did not reveal any statistically significant differences with regard to CNA frequency or type. Of the 191 genes within the target region, two novel recurrent mutations were found in the MELK and PDCD1LG2 genes. The most commonly mutated gene in sarcomas was TLN1 (8%) and PAX5 in ALL (9%). Mutations in PAX5, and RUSC2, were seen exclusively in ALL patients and those in KIAA1432, CA9, TLN1, and MELK only in sarcomas (MFH, FS, EFT). Thus using targeted NGS of the 9p region, in addition to commonly deleted CDKN2A locus, we were able to identify a number of small deletions and gains, as well as novel recurrent mutations in different cancer types. © 2014 Wiley Periodicals, Inc. 相似文献
23.
Anu-Katriina Pesonen Katri Räikkönen E. Juulia Paavonen Kati Heinonen Niina Komsi Jari Lahti Eero Kajantie Anna-Liisa Järvenpää Timo Strandberg 《International journal of behavioral medicine》2010,17(4):298-305
Background
Relatively little is known about the significance of normal variation in objectively assessed sleep duration and its regularity in children's psychological well-being. 相似文献24.
L B Hinshaw B K Beller A C Chang R B Passey R A Lahti D J Flournoy M M Lane L T Archer 《Surgery, gynecology & obstetrics》1986,163(4):335-344
The effects upon survival of large doses of steroid administered to dogs prior to challenging them with lethal sepsis was evaluated in this study. Dogs were given 30 milligrams per kilogram of body weight per day of methylprednisolone sodium succinate for one, two or eight days and then were infused with 9.72 +/- 0.35 X 10(9) Escherichia coli per kilogram of body weight. All dogs in group 1 (n equals six) not given steroid died within 25 hours. Of the dogs in group 2 (n equals 12) given one or two doses of steroid previously, 42 per cent permanently survived (more than seven days). All dogs in group 3 (n equals five) given eight daily doses of steroid prior to infusion of Escherichia coli died within 17 hours. Dogs in group 4 (n equals six) were given eight daily doses of steroid prior to infusion of Escherichia coli and treated on the day of infusion of Escherichia coli with a regimen of methylprednisolone and gentamicin sulfate which results in a 100 per cent survival rate when given to dogs that have not received prior treatment with steroid. Thirty-three per cent of the dogs in group 4 permanently survived. One or two daily large doses of steroid did not detrimentally affect survival of the dogs. Eight days of steroid administration suppressed endogenous cortisol production. When the dogs were treated with six hours of steroid-antibiotic therapy, survival benefits were limited. 相似文献
25.
Tienari P Wynne LC Läksy K Moring J Nieminen P Sorri A Lahti I Wahlberg KE 《The American journal of psychiatry》2003,160(9):1587-1594
OBJECTIVE: Identification of the genetically related disorders in the putative schizophrenia spectrum is an unresolved problem. Data from the Finnish Adoptive Family Study of Schizophrenia, which was designed to disentangle genetic and environmental factors influencing risk for schizophrenia, were used to examine clinical phenotypes of schizophrenia spectrum disorders in adopted-away offspring of mothers with schizophrenia spectrum disorders. METHOD: Subjects were 190 adoptees at broadly defined genetic high risk who had biological mothers with schizophrenia spectrum disorders, including a subgroup of 137 adoptees at narrowly defined high risk whose mothers had DSM-III-R schizophrenia. These high-risk groups, followed to a median age of 44 years, were compared diagnostically with 192 low-risk adoptees whose biological mothers had either a non-schizophrenia-spectrum diagnosis or no lifetime psychiatric diagnosis. RESULTS: In adoptees whose mothers had schizophrenia, the mean lifetime, age-corrected morbid risk for narrowly defined schizophrenia was 5.34% (SE=1.97%), compared to 1.74% (SE=1.00%) for low-risk adoptees, a marginally nonsignificant difference. In adoptees whose mothers had schizophrenia spectrum disorders, the mean age-corrected morbid risk for a schizophrenia spectrum disorder was 22.46% (SE=3.56%), compared with 4.36% (SE=1.51%) for low-risk adoptees, a significant difference. Within the comprehensive array of schizophrenia spectrum disorders, schizotypal personality disorder was found significantly more often in high-risk than in low-risk adoptees. The frequency of the group of nonschizophrenic nonaffective psychoses collectively differentiated high-risk and low-risk adoptees, but the frequencies of the separate disorders within this category did not. The two groups were not differentiated by the prevalence of paranoid personality disorder and of affective disorders with psychotic features. CONCLUSIONS: In adopted-away offspring of mothers with schizophrenia spectrum disorders, the genetic liability for schizophrenia-related illness (with the rearing contributions of the biological mothers disentangled) is broadly dispersed. Genetically oriented studies of schizophrenia-related disorders and studies of genotype-environment interaction should consider not only narrowly defined, typical schizophrenia but also schizotypal and schizoid personality disorders and nonschizophrenic nonaffective psychoses. 相似文献
26.
Teitz T Wei T Liu D Valentine V Valentine M Grenet J Lahti JM Kidd VJ 《Oncogene》2002,21(12):1848-1858
Important roles have been suggested for caspase-8, caspase-9 and Apaf-1 in controlling tumor development and their sensitivity to chemotherapeutic agents. Methylation and deletion of Apaf-1 and CASP8 results in the loss of their expression in melanoma and neuroblastoma, respectively, while CASP9 localization to 1p36.1 suggests it is a good candidate tumor suppressor. The status of CASP9 and Apaf-1 expression in numerous neuroblastoma cell lines with/without amplified MYCN and chromosome 1p36 loss-of-heterozygosity (LOH) was therefore examined to test the hypothesis that one or both of these genes are tumor suppressors in neuroblastoma. Although CASP9 is included in the region encompassing 1p36 LOH in all neuroblastoma cell lines examined, the remaining CASP9 allele(s) express a functional caspase-9 enzyme. Apaf-1 is also expressed in all neuroblastoma tumor cell lines examined. Thus, the CASP9 or Apaf-1 genes do not appear to function as tumor suppressors in MYCN amplified neuroblastomas. However, approximately 20% of the neuroblastoma cell lines with methylated CASP8 alleles are also highly resistant to staurosporine (STS)- and radiation-induced cell death, presumably because cytochrome c is not released from mitochondria. This suggests that a second, smaller sub-group of MYCN amplified neuroblastoma tumors exists with defect(s) in apoptotic signaling components upstream of caspase-9 and Apaf-1. Since no consistent differences in Bcl-2, Bcl-x(L) or Bax expression were seen in the STS- and radiation-resistant neuroblastomas, it suggests that a unique mitochondrial signaling factor(s) is responsible for the defect in cytochrome c release in this sub-group of tumors. 相似文献
27.
28.
Rapala J Robertson A Negri AP Berg KA Tuomi P Lyra C Erkomaa K Lahti K Hoppu K Lepistö L 《Environmental toxicology》2005,20(3):331-340
This study is the first report of saxitoxin in cyanobacterial blooms in Finland. Bloom samples (n = 50) were collected from Finnish freshwater sites during summer months of 2002 and 2003. These samples were screened for the presence of paralytic shellfish toxins (PSTs) using the Jellett rapid PSP screening test. Samples testing positive for PSTs (n = 7) were further analyzed with saxiphilin- and voltage-gated sodium channel [(3)H]-STX-binding radioreceptor assays and liquid chromatography using fluorescence and mass spectrometric analysis. The results indicated that saxitoxin (STX) was the only PST analogue in the samples and that it was present in high concentrations, as much as 1 mg L(-1). Microscopic analysis revealed that 95%-100% of the phytoplankton in the positive samples consisted of Anabaena lemmermannii. The trophic status of lakes in which STX-containing blooms were found varied from oligotrophic to hypertrophic. All the lakes had high nitrogen-to-phosphorus ratios. In some instances, samples had been collected from sites where swimmers had reported adverse health effects, and in three such cases, reported adverse health effects were associated with sites from which samples testing positive for STX had been received. Symptoms of fever, eye irritation, abdominal pains, and skin rash were reported in children aged 2-10 years after exposure to the water. These were not the adverse human symptoms typical of STX poisoning; rather, they represented acute effects often reported following recreational exposure to cyanobacterial blooms. 相似文献
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30.
Steele JG Sanders AE Slade GD Allen PF Lahti S Nuttall N Spencer AJ 《Community dentistry and oral epidemiology》2004,32(2):107-114
Age and loss of teeth can be expected to have a complex relationship with oral health-related quality of life. This study aimed to explain how age and tooth loss affect the impact of oral health on daily living using the short form, 14-item Oral Health Impact Profile (OHIP-14) on national population samples of dentate adults from the UK (1998 UK Adult Dental Health Survey) and Australia (1999 National Dental Telephone Interview Survey). After correcting for key covariables, increasing age was associated with better mean impact scores in both populations. Those aged 30-49 years in Australia showed the worst (highest) scores. In the UK, those aged under 30 showed the highest scores. In both countries, adults aged 70+ showed much better scores than the rest (P < 0.001). When corrected for age, the independent effect of tooth loss was that the worst scores were found where there were fewer than 17 natural teeth in the UK and fewer than 21 teeth in Australia. People with 25 or more teeth averaged much better scores than all other groups (P < 0.001), although there were differences in pattern between countries. When Australians were analysed by region of birth, the pattern of scores by tooth loss for British/Irish immigrants was strikingly similar to that for the UK sample. First-generation immigrants from elsewhere showed much worse overall scores and a profoundly different pattern to the Australian- and British-born groups. Age, number of teeth and cultural background are important variables influencing oral health-related quality of life. 相似文献