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排序方式: 共有957条查询结果,搜索用时 15 毫秒
81.
Saarinen A Välimäki VV Välimäki MJ Löyttyniemi E Auro K Uusen P Kuris M Lehesjoki AE Mäkitie O 《BONE》2007,40(4):1006-1012
INTRODUCTION: Polymorphisms in the gene coding for low-density lipoprotein receptor-related protein 5 (LRP5) contribute to variation in bone mass in the general population. Whether this is due to influence on bone mass acquisition or on bone loss thereafter has not been established. METHODS: We studied the association of LRP5 polymorphisms with peak bone mass in young men. The study included 235 Finnish men, aged 18.3 to 20.6 years. Lifestyle factors and fracture history were recorded. Bone mineral content (BMC), density (BMD) and scan area were measured for the lumbar spine and proximal femur by dual energy X-ray absorptiometry (DXA). Blood and urine were collected for determination of bone turnover markers, serum 25-OHD and PTH. Genomic DNA was extracted from peripheral blood for genetic analysis of LRP5. Ten single nucleotide polymorphisms in LRP5 were analyzed and correlated with bone parameters. RESULTS: Only the A1330V polymorphism of LRP5 significantly associated with bone parameters. In comparison with subjects with the AlaAla genotype (n=215), those with AlaVal genotype (n=20) had lower femoral neck BMC (P=0.029) and BMD (P=0.012), trochanter BMC (P=0.0067) and BMD (P=0.015), and total hip BMC (P=0.0044) and BMD (P=0.0089). Fracture history was similar for the genotypes. CONCLUSION: The polymorphic valine variant at position 1330 of LRP5 was significantly associated with reduced BMC and BMD values in healthy young Finnish men. The results provide evidence for the crucial role of LRP5 in peak bone mass acquisition. 相似文献
82.
Nellist M van den Heuvel D Schluep D Exalto C Goedbloed M Maat-Kievit A van Essen T van Spaendonck-Zwarts K Jansen F Helderman P Bartalini G Vierimaa O Penttinen M van den Ende J van den Ouweland A Halley D 《European journal of human genetics : EJHG》2009,17(3):319-328
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterised by the development of hamartomas in a variety of organs and tissues. The disease is caused by mutations in either the TSC1 gene on chromosome 9q34 or the TSC2 gene on chromosome 16p13.3. The TSC1 and TSC2 gene products, TSC1 and TSC2, interact to form a protein complex that inhibits signal transduction to the downstream effectors of the mammalian target of rapamycin (mTOR). Here we investigate the effects of putative TSC1 missense mutations identified in individuals with signs and/or symptoms of TSC on TSC1-TSC2 complex formation and mTOR signalling. We show that specific amino-acid substitutions close to the N-terminal of TSC1 reduce steady-state levels of TSC1, resulting in the activation of mTOR signalling and leading to the symptoms of TSC. 相似文献
83.
A TLR4 polymorphism is associated with asthma and reduced lipopolysaccharide-induced interleukin-12(p70) responses in Swedish children 总被引:11,自引:0,他引:11
Fagerås Böttcher M Hmani-Aifa M Lindström A Jenmalm MC Mai XM Nilsson L Zdolsek HA Björkstén B Söderkvist P Vaarala O 《The Journal of allergy and clinical immunology》2004,114(3):561-567
BACKGROUND: Bacterial signals play an important role in the maturation of the immune system. Polymorphisms in genes coding for receptors to bacterial components can alter the immune responsiveness of the host to microbial agents and may indicate the development of aberrant immune responses that are associated with immune-mediated diseases such as atopic diseases. OBJECTIVE: The study's objective was to investigate the relationship between TLR4 and CD14 gene polymorphisms, the LPS responsiveness of PBMCs, and the presence of asthma and allergic rhinoconjunctivitis in children. METHODS: The TLR4 (Asp299Gly) and CD14/-159 polymorphisms were determined in 115 Swedish children aged 8 and 14 years. LPS-induced IL-12(p70), IL-10, and IFN-gamma responses of PBMCs from 69 of the children were analyzed by means of ELISA. The levels of soluble CD14 in serum samples were analyzed by means of ELISA, and the total IgE levels were analyzed by means of UniCAP Total IgE (Pharmacia Diagnostics, Uppsala, Sweden). RESULTS: Decreased LPS-induced IL-12(p70) and IL-10 responses were associated with the TLR4 (Asp299Gly) polymorphism and independently with asthma, especially atopic asthma. The TLR4 (Asp299Gly) polymorphism was associated with a 4-fold higher prevalence of asthma in school-aged children (adjusted odds ratio 4.5, 95% CI 1.1-17.4) but not to allergic rhinoconjunctivitis. CONCLUSION: A TLR4 polymorphism modifies innate immune responses in children and may be an important determinant for the development of asthma. This may influence the outcome of intervention studies that use microbial stimuli as immune modulators. 相似文献
84.
85.
Bharti Razdan Peter J. Marro Outi Tammela Rajiv Goel Om Prakash Mishra Maria Delivoria-Papadopoulos 《Brain research》1993,600(2):308-314
The effect of hypoxia on the structure and function of the synaptosomal membranes and myelin fraction (glial cells, neuronal cell bodies and axonal membranes) was investigated by measuring Na+,K+-ATPase activity and levels of lipid peroxidation products in cerebral cortical synaptosomal membranes and myelin fractions obtained from newborn piglets. Hypoxic hypoxia was induced and cerebral hypoxia was documented as a decrease in the ratio of phosphocreatine to inorganic phosphate (PCr/Oi) using31P-NMR spectroscopy. PCr/Pi decreased from baseline of2.93 ± 0.76to0.61 ± 0.36 during hypoxia. The synaptosomal membrane Na+,K+-ATPase activity decreased from a control value of56.6 ± 3.7to40.4 ± 6.0 μgmol Pi/mg protein/h during hypoxia. The level of conjugated dienes increased from zero (reference value) to4.5 ± 2.7 nmol/mg lipid and the level of fluorescent compounds increased from23.5 ± 2.2to92.6 ± 46.4 ng quinine sulfate/mg lipid in the synaptosomal membranes during hypoxia. No change in myelin fraction Na+,K+-ATPase activity or levels of lipid peroxidation products were noted. These data indicate that sunaptosomal membranes, rich in polyunsaturated fatty acids, are more susceptible to oxygen free radical mediated lipid peroxidative damage during hypoxia. 相似文献
86.
Kaukola T Satyaraj E Patel DD Tchernev VT Grimwade BG Kingsmore SF Koskela P Tammela O Vainionpää L Pihko H Aärimaa T Hallman M 《Annals of neurology》2004,55(2):186-194
Cerebral palsy (CP) is a major neurodevelopmental disability in childhood. An association between intrauterine infection and CP has been reported. We examined the relationship between inflammatory mediators in cord serum and CP in term and preterm children. Regional multicenter study was conducted on 19 CP children and 19 gestation-matched paired controls. CP children (n = 27) were further compared with controls of similar gestation at birth (n = 25). Serum levels of 78 protein mediators were analyzed. Eleven analytes correlated with the length of gestation both in cases and controls. In paired analysis, B-lymphocyte chemoattractant, ciliary neurotrophic factor, epidermal growth factor, interleukin (IL)-5, IL-12, IL-13, IL-15, macrophage migration inhibitory factor, monocyte chemoattractant protein-3, monokine induced by interferon gamma, and tumor necrosis factor-related apoptosis-inducing ligand were higher in children with CP (p < or = 0.05). Preterm infants with CP showed higher epidermal growth factor and lower levels of granulocyte-macrophage colony-stimulating factor, IL-2, macrophage-derived chemokine, and pulmonary and activation-regulated chemokine than their paired controls. Inflammatory mediators and growth factors serve as a footprint of the fetal response to an insult manifesting after birth as a permanent brain damage. The cytokine patterns at birth differ between premature and term infants who develop CP. 相似文献
87.
A meta-analysis of human embryonic stem cells transcriptome integrated into a web-based expression atlas 总被引:2,自引:0,他引:2
88.
Keiju S. K. Kontula Kirsi Skogberg Jukka Ollgren Asko Järvinen Outi Lyytikäinen 《European journal of clinical microbiology & infectious diseases》2018,37(5):945-952
Few studies covering all patient groups and specialties are available regarding the outcome of nosocomial bloodstream infections (BSI). We analyzed the role of patient characteristics and causative pathogens of nosocomial BSIs reported by the hospitals participating in national surveillance in Finland during 1999–2014, in terms of outcome, with particular interest in those leading to death within 2 days (i.e. early death). National nosocomial BSI surveillance was laboratory-based and hospital-wide. Data on nosocomial BSIs was collected by infection control nurses, and dates of death were obtained from the national population registry with linkage to national identity codes. A total of 17,767 nosocomial BSIs were identified; 557 BSIs (3%) were fatal within 2 days and 1150 (6%) within 1 week. The 1-month case fatality was 14% (2460 BSIs), and 23% of the deaths occurred within 2 days and 47% within 1 week. The patients who died early were older than those who survived >?28 days, and their BSIs were more often related to intensive care. Gram-positive bacteria caused over half of the BSIs of patients who survived, whereas gram-negative bacteria, especially Pseudomonas aeruginosa, caused more often BSIs of patients who died early, and fungi BSIs of patients who died within 1 week. A significant portion of patients with nosocomial BSIs died early, which underlines the importance of rapid recognition of BSI. Hospital-wide surveillance data of causative pathogens can be utilized when composing recommendations for empiric antimicrobial treatment in collaboration with clinicians, as well as when promoting infection prevention. 相似文献
89.
Elisa J. Pulczynski Outi Kuittinen Martin Erlanson Hans Hagberg Alexander Foss? Mikael Eriksson Marie Nordstr?m Bj?rn ?stenstad ?ystein Fluge Sirpa Lepp? Bente Fiirgaard Hanne Bersvendsen Unn-Merete Fagerli 《Haematologica》2015,100(4):534-540
The Nordic Lymphoma Group has conducted a phase ll trial in newly diagnosed primary central nervous system lymphoma patients applying an age-adjusted multi-agent immunochemotherapy regimen, which in elderly patients included temozolomide maintenance treatment. Patients aged 18–75 years were eligible. Thirty-nine patients aged 18–65 years and 27 patients aged 66–75 years were enrolled. The median age of the two age groups was 55 and 70 years, respectively. The overall response rate was 73.8% for the entire cohort: 69.9% in the younger and 80.8% in the elderly subgroup. With a median follow up of 22 months, the 2-year overall survival probability was 60.7% in patients aged 65 years or under and 55.6% in patients aged over 65 years (P=0.40). The estimated progression-free survival at two years was 33.1% (95%CI: 19.1%–47.9%) in patients aged under 65 years and 44.4% (95%CI: 25.6%–61.8%) in the elderly subgroup (P=0.74). Median duration of response was ten months in the younger subgroup, and not reached in the elderly patient subgroup (P=0.33). Four patients aged 64–75 years (6%) died from treatment-related complications. Survival in the two age groups was similar despite a de-escalation of induction treatment in patients aged over 65 years. Duration of response in elderly patients receiving maintenance temozolomide was longer than in the younger age subgroup. While toxicity during induction is still of concern, especially in the elderly patients, we conclude from these data that de-escalation of induction therapy in elderly primary central nervous system lymphoma patients followed by maintenance treatment seems to be a promising treatment strategy. (clinicaltrials.gov identifier:01458730) 相似文献
90.