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1.
Bruce A. C. Cree John D. Rioux Jacob L. McCauley Pierre-Antoine F. D. Gourraud Philippe Goyette Joseph McElroy Philip De Jager Adam Santaniello Timothy J. Vyse Peter K. Gregersen Daniel Mirel David A. Hafler Jonathan L. Haines Margaret A. Pericak-Vance Alastair Compston Stephen J. Sawcer Jorge R. Oksenberg Stephen L. Hauser IMAGEN IMSGC 《PloS one》2010,5(6)
Background
In Northern European descended populations, genetic susceptibility for multiple sclerosis (MS) is associated with alleles of the human leukocyte antigen (HLA) Class II gene DRB1. Whether other major histocompatibility complex (MHC) genes contribute to MS susceptibility is controversial.Methodology/Principal Findings
A case control analysis was performed using 958 single nucleotide polymorphisms (SNPs) spanning the MHC assayed in two independent datasets. The discovery dataset consisted of 1,018 cases and 1,795 controls and the replication dataset was composed of 1,343 cases and 1,379 controls. The most significantly MS-associated SNP in the discovery dataset was rs3135391, a Class II SNP known to tag the HLA-DRB1*15:01 allele, the primary MS susceptibility allele in the MHC (O.R. = 3.04, p<1×10−78). To control for the effects of the HLA-DRB1*15:01 haplotype, case control analysis was performed adjusting for this HLA-DRB1*15:01 tagging SNP. After correction for multiple comparisons (false discovery rate = .05) 52 SNPs in the Class I, II and III regions were significantly associated with MS susceptibility in both datasets using the Cochran Armitage trend test. The discovery and replication datasets were merged and subjects carrying the HLA-DRB1*15:01 tagging SNP were excluded. Association tests showed that 48 of the 52 replicated SNPs retained significant associations with MS susceptibility independently of the HLA-DRB1*15:01 as defined by the tagging SNP. 20 Class I SNPs were associated with MS susceptibility with p-values ≤1×10−8. The most significantly associated SNP was rs4959039, a SNP in the downstream un-translated region of the non-classical HLA-G gene (Odds ratio 1.59, 95% CI 1.40, 1.81, p = 8.45×10−13) and is in linkage disequilibrium with several nearby SNPs. Logistic regression modeling showed that this SNP''s contribution to MS susceptibility was independent of the Class II and Class III SNPs identified in this screen.Conclusions
A MHC Class I locus contributes to MS susceptibility independently of the HLA-DRB1*15:01 haplotype. 相似文献2.
Angelique H?lzemer Christina F. Thobakgale Camilo A. Jimenez Cruz Wilfredo F. Garcia-Beltran Jonathan M. Carlson Nienke H. van Teijlingen Jaclyn K. Mann Manjeetha Jaggernath Seung-gu Kang Christian K?rner Amy W. Chung Jamie L. Schafer David T. Evans Galit Alter Bruce D. Walker Philip J. Goulder Mary Carrington Pia Hartmann Thomas Pertel Ruhong Zhou Thumbi Ndung’u Marcus Altfeld 《PLoS medicine》2015,12(11)
Background
Viruses can evade immune surveillance, but the underlying mechanisms are insufficiently understood. Here, we sought to understand the mechanisms by which natural killer (NK) cells recognize HIV-1-infected cells and how this virus can evade NK-cell-mediated immune pressure.Methods and Findings
Two sequence mutations in p24 Gag associated with the presence of specific KIR/HLA combined genotypes were identified in HIV-1 clade C viruses from a large cohort of infected, untreated individuals in South Africa (n = 392), suggesting viral escape from KIR+ NK cells through sequence variations within HLA class I—presented epitopes. One sequence polymorphism at position 303 of p24 Gag (TGag303V), selected for in infected individuals with both KIR2DL3 and HLA-C*03:04, enabled significantly better binding of the inhibitory KIR2DL3 receptor to HLA-C*03:04-expressing cells presenting this variant epitope compared to the wild-type epitope (wild-type mean 18.01 ± 10.45 standard deviation [SD] and variant mean 44.67 ± 14.42 SD, p = 0.002). Furthermore, activation of primary KIR2DL3+ NK cells from healthy donors in response to HLA-C*03:04+ target cells presenting the variant epitope was significantly reduced in comparison to cells presenting the wild-type sequence (wild-type mean 0.78 ± 0.07 standard error of the mean [SEM] and variant mean 0.63 ± 0.07 SEM, p = 0.012). Structural modeling and surface plasmon resonance of KIR/peptide/HLA interactions in the context of the different viral sequence variants studied supported these results. Future studies will be needed to assess processing and antigen presentation of the investigated HIV-1 epitope in natural infection, and the consequences for viral control.Conclusions
These data provide novel insights into how viruses can evade NK cell immunity through the selection of mutations in HLA-presented epitopes that enhance binding to inhibitory NK cell receptors. Better understanding of the mechanisms by which HIV-1 evades NK-cell-mediated immune pressure and the functional validation of a structural modeling approach will facilitate the development of novel targeted immune interventions to harness the antiviral activities of NK cells. 相似文献3.
Mi-Hye Hwang Xiu Juan Li Jung Eun Kim Shin Young Jeong Sang-Woo Lee Jaetae Lee Byeong-Cheol Ahn 《PloS one》2015,10(8)
Objective
The aim of this study was to explore the therapeutic effect of natural killer (NK) cells on human doxorubicin-sensitive and resistant breast adenocarcinoma.Methods
Human doxorubicin-sensitive and resistant breast cancer cell lines (MCF-7 and MCF-7/ADR) were tagged with renilla luciferase (Rluc) (MCF-7/RC and MCF-7/ADR/RC). NK cells were tagged with enhanced firefly luciferase (effluc) using a recombinant retrovirus transfection (NKF). Expression of Rluc, effluc, and NK cell surface markers CD16, CD56 as well as death receptors, DR4 and DR5, were assessed by using flow cytometry. In vitro cytotoxic effect of NK to MCF-7 and MCF-7/ADR was measured and in vivo bioluminescence imaging was also performed to visualize MCF-7/RC, MCF-7/ADR, and NKF in an animal model.Results
NK92-MI, MCF-7, and MCF-7/ADR cells were successfully labeled with Rluc or effluc. Both the target breast cancer cells (with Rluc) and therapeutic NK cells (with effluc) were noninvasively visualized in nude mice. Doxorubicin-resistant breast cancer cells (MCF-7/ADR) presented a higher expression of DR5 and were more sensitive to NK cells compared with doxorubicin-sensitive breast cancer cells (MCF-7).Conclusion
The results of present study suggest that NK cell therapy has a therapeutic effect on doxorubicin-sensitive and resistant breast cancer cells. 相似文献4.
Background
Butyrophilin-like 2 (BTNL2) rs2076530 gene polymorphism has been implicated in susceptibility to sarcoidosis. However, results from previous studies are not consistent. To assess the association of BTNL2 polymorphism and sarcoidosis susceptibility, a meta-analysis was performed.Methods
PubMed, Embase were searched for eligible case-control studies. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated.Results
Ten studies involving a total of 3303 cases and 2514 controls were included in this meta-analysis. Combined data indicated that BTNL2 rs2076530 polymorphism was associated with sarcoidosis susceptibility in allelic model (A vs. G, OR = 1.59, 95%CI: 1.47–1.72), dominant model (AA + AG vs. GG, OR = 2.10, 95%CI: 1.67–2.65), and recessive model (AA vs. AG + GG, OR = 1.93, 95%CI: 1.49–2.50).Conclusions
This meta-analysis indicates that BTNL2 rs2076530 polymorphism contributes to the risk of sarcoidosis. 相似文献5.
Marc B. Bigler Simon B. Egli Cédric M. Hysek Gideon Hoenger Laurent Schmied Fabian S. Baldin Florian A. Marquardsen Mike Recher Matthias E. Liechti Christoph Hess Christoph T. Berger 《PloS one》2015,10(12)
Background
Acute stress drives a ‘high-alert’ response in the immune system. Psychoactive drugs induce distinct stress hormone profiles, offering a sought-after opportunity to dissect the in vivo immunological effects of acute stress in humans.Methods
3,4-methylenedioxymethamphetamine (MDMA), methylphenidate (MPH), or both, were administered to healthy volunteers in a randomized, double-blind, placebo-controlled crossover-study. Lymphocyte subset frequencies, natural killer (NK) cell immune-phenotypes, and changes in effector function were assessed, and linked to stress hormone levels and expression of CD62L, CX3CR1, CD18, and stress hormone receptors on NK cells.Results
MDMA/MPH > MDMA > MPH robustly induced an epinephrine-dominant stress response. Immunologically, rapid redistribution of peripheral blood lymphocyte-subsets towards phenotypically mature NK cells occurred. NK cytotoxicity was unaltered, but they expressed slightly reduced levels of the activating receptor NKG2D. Preferential circulation of mature NK cells was associated with high epinephrine receptor expression among this subset, as well as expression of integrin ligands previously linked to epinephrine-induced endothelial detachment.Conclusion
The acute epinephrine-induced stress response was characterized by rapid accumulation of mature and functional NK cells in the peripheral circulation. This is in line with studies using other acute stressors and supports the role of the acute stress response in rapidly mobilizing the innate immune system to counteract incoming threats. 相似文献6.
Hannes Vietzen Svenja Hartenberger Stephan W. Aberle Elisabeth Puchhammer-Stckl 《PLoS neglected tropical diseases》2021,15(12)
BackgroundInfections with the Puumala orthohantavirus (PUUV) in humans may cause hemorrhagic fever with renal syndrome (HFRS), known as nephropathia epidemica (NE), which is associated with acute renal failure in severe cases. In response to PUUV-infections, a subset of potent antiviral NKG2C+ NK cells expand, whose role in virus defence and pathogenesis of NE is unclear. NKG2C+ NK cell proliferation is mediated by binding of NKG2C/CD94 to HLA-E on infected cells. The proliferation and activation of NKG2C+ NK cells via the NKG2C/HLA-E axis is affected by different NKG2C (NKG2Cwt/del) and HLA-E (HLA-E*0101/0103) alleles, which naturally occur in the human host. Homozygous (NKG2Cdel/del) and heterozygous (NKG2Cwt/del) deletions of the NKG2C receptor results in an impaired NKG2C/CD94 mediated proliferation and activation of NKG2C+ cells. We therefore analyzed the PUUV-mediated NKG2C+ NK cell responses and the impact of different NKG2C and HLA-E alleles in NE patients.Methodology/Principal findingsNKG2C+ NK cell expansion and effector functions in PUUV-infected cells were investigated using flow cytometry and it was shown that PUUV-infected endothelial cells led to a NKG2C/CD94 mediated NKG2C+ NK cell activation and expansion, dependent on the HLA-G-mediated upregulation of HLA-E. Furthermore, the NKG2Cdel and HLA-E*0101/0103 alleles were determined in 130 NE patients and 130 matched controls, and it was shown that in NE patients the NKG2Cwt/del allele was significantly overrepresented, compared to the NKG2Cwt/wt variant (p = 0.01). In addition, in vitro analysis revealed that NKG2Cwt/del NK cells exhibited on overall a lower proliferation (p = 0.002) and lower IFNγ expression (p = 0.004) than NKG2Cwt/wt NK cells.Conclusions/SignificanceOur results corroborate the substantial impact of the NKG2C/HLA-E axis on PUUV-specific NK cell responses. A weak NKG2C+ NK cell response, as reflected by NKG2Cwt/del variant, may be associated with a higher risk for a severe hantavirus infections. 相似文献
7.
This study compared the effects of the human 70-kDa stress protein (Hsp70) peptide, TKDNNLLGRFELSG (TKD), proinflammatory
cytokines, or a combination of both on the repertoire of receptors expressed by human natural killer (NK) cells and their
capacity to kill human CX colon carcinoma cells, K562 erythroleukemic cells, and leukemic blasts from two patients with acute
myelogenous leukemia. Low-dose interleukin (IL) 2/IL-15 and TKD increase the expression density of activatory (NKG2D, NKp30,
NKp44, NKp46, CD94/NKG2C) and inhibitory (CD94/NKG2A) receptors on NK cells. Concomitantly, IL-2/TKD treatment enhances the
cytotoxicity of NK cells (as reflected by their secretion of granzyme B) against Hsp70 membrane-positive and human leukocyte
antigen (HLA)-E membrane-negative (Hsp70+/HLA-E−) CX+ and K562 cells. However, it had no effect on the responsiveness to Hsp70−/HLA-E− CX− cells over that induced by IL-2 alone. The cytotoxicity of IL-2/TKD-activated, purified NK cells and peripheral blood mononuclear
cells against Hsp70+/HLA-E+ leukemic blasts was weaker than that against Hsp70+/HLA-E− K562 cells. Hsp70-blocking and HLA-E transfection experiments confirmed membrane-bound Hsp70 as being a recognition/activatory
ligand for NK cells, as cytotoxicity was reduced by the presence of the anti-Hsp70 monoclonal antibody cmHsp70.2 and by inhibiting
Hsp70 synthesis using short interference ribonucleic acid. HLA-E was confirmed as an inhibitory ligand, as the extent of NK
cell-mediated lysis of K562 cell populations that had been transfected with HLA-ER or HLA-EG alleles was dependent on the proportion of HLA-E-expressing cells. These findings indicate that Hsp70 (as an activatory molecule)
and HLA-E (as an inhibitory ligand) expression influence the susceptibility of leukemic cells to the cytolytic activities
of cytokine/TKD-activated NK cells. 相似文献
8.
Kumud K. Singh Min Qin Sean S. Brummel Konstantia Angelidou Rodney N. Trout Terence Fenton Stephen A. Spector 《PloS one》2016,11(3)
Background
HLA class I molecules are ligands for killer cell immunoglobin like receptors (KIR) that control the antiviral response of natural killer (NK) cells. However, the effects of KIR and HLA (KIR/HLA) alleles on HIV disease of children have not been studied.Methods
993 antiretroviral naïve children with symptomatic HIV infection from PACTG protocols P152 and P300 were genotyped for KIR and HLA alleles using the Luminex platform. Linear regression was used to test the association between genotypes and baseline pre-ART HIV RNA, CD4+ lymphocyte count, and cognitive score, adjusting for age, race/ethnicity and study. The interaction between genetic markers and age was investigated. To account for multiple testing the false discovery rate (FDR) was controlled at 0.05.Results
Children with the KIR2DS4*ALL FULL LENGTH (KIR2DS4*AFL) allele had higher CD4+ lymphocyte counts. Among children ≤2 years of age, the KIR2DS4*AFL was associated with lower plasma HIV RNA and higher cognitive index scores. KIR Cent2DS3/5_1 had lower CD4+ lymphocyte counts in children ≤2 years of age, while the presence of Tel1, Tel2DS4_2, Tel2DS4_4, Tel8, Tel2DS4_6 had higher CD4+ lymphocyte counts in all children. Presence of Cent2, Cent4 and Cent8 was associated with increased HIV RNA load in children ≤2 years. Presence of KIR3DL1+Bw4 was associated with higher CD4+ lymphocyte counts in all children. Among children >2 years old, KIR3DS1+Bw4-80I was associated with higher plasma HIV RNA, and Bw6/Bw6 was associated with lower plasma HIV RNA compared to children with KIR3DS1+Bw4-80I.Conclusions
Presented data show for the first time that specific KIR alleles independently or combined with HLA ligands are associated with HIV RNA and CD4+ lymphocyte counts in infected, antiretroviral naive children; and many of these effect estimates appear to be age dependent. These data support a role for specific KIR alleles in HIV pathogenesis in children. 相似文献9.
Eero Lauhkonen Petri Koponen Johanna Ter?sj?rvi Kirsi Gr?ndahl-Yli-Hannuksela Juho Vuononvirta Kirsi Nuolivirta Jyri O. Toikka Merja Helminen Qiushui He Matti Korppi 《PloS one》2015,10(10)
Aim
Interleukin-10 (IL-10) has been associated with wheezing and asthma in children and the genetic variation of the IL-10 cytokine production may be linked to post-bronchiolitis lung function. We used impulse oscillometry (IOS) to evaluate the associations of IL10 polymorphisms with lung function at a median age of 6.3 years in children hospitalised for bronchiolitis before six months of age.Methods
We performed baseline and post-exercise IOS on 103 former bronchiolitis patients. Data on single nucleotide polymorphisms (SNP) of IL10 rs1800896 (–1082G/A), rs1800871 (–819C/T), rs1800872 (–592C/A) were available for 99 children and of IL10 rs1800890 (–3575T/A) for 98 children.Results
IL10 rs1800896, rs1800871 and rs1800872 combined genotype AA+CT+CA and carriage of haplotype ATA, respectively, were associated with higher resistance and lower reactance in baseline IOS in adjusted analyses. At IL10 rs1800890, the A/A-genotype and carriers of A-allele were associated with lower reactance in baseline IOS. There were no significant associations between the studied SNPs and airway hyper-reactivity to exercise.Conclusion
Low-IL-10-producing polymorphisms in the IL-10 encoding gene were associated with obstructive lung function parameters, suggesting an important role for IL-10 in development of lung function deficit in early bronchiolitis patients. 相似文献10.
Anusha van Samkar Matthijs C. Brouwer Constance Schultsz Arie van der Ende Diederik van de Beek 《PLoS neglected tropical diseases》2015,9(10)
Background
Streptococcus suis is the most common cause of meningitis in pork consuming and pig rearing countries in South-East Asia. We performed a systematic review of studies on S. suis meningitis to define the clinical characteristics, predisposing factors and outcome.Methodology
Studies published between January 1, 1980 and August 1, 2015 were identified from main literature databases and reference lists. Studies were included if they were written in West-European languages and described at least 5 adult patients with S. suis meningitis in whom at least one clinical characteristic was described.Findings
We identified 913 patients with S. suis meningitis included in 24 studies between 1980 and 2015. The mean age was 49 years and 581 of 711 patients were male (82%). Exposure to pigs or pork was present in 395 of 648 patients (61%) while other predisposing factors were less common. 514 of 528 patients presented with fever (97%), 429 of 451 with headache (95%), 462 of 496 with neck stiffness (93%) and 78 of 384 patients (20%) had a skin injury in the presence of pig/pork contact. The case fatality rate was 2.9% and hearing loss was a common sequel occurring in 259 of 489 patients (53%). Treatment included dexamethasone in 157 of 300 (52%) of patients and was associated with reduced hearing loss in S. suis meningitis patients included in a randomized controlled trial.Conclusion
S. suis meningitis has a clear association with pig and pork contact. Mortality is low, but hearing loss occurs frequently. Dexamethasone was shown to reduce hearing loss. 相似文献11.
Sivan Shamai Ilana Nabiochtchikov Sarah Kraus Sally Zigdon Dina Kazanov Michal Itzhak-Klutch Carmit Eizner Nadir Arber Ravit Geva 《PloS one》2015,10(9)
Background
There are no validated biomarkers that correlate with the prognosis of pancreatic ductal adenocarcinoma (PDA). The CD24 and adenomatous polyposis coli (APC) genes are important in the malignant transformation of gastrointestinal cells. This study examined APC and CD24 genetic polymorphisms and their possible impact on survival of patients with PDA.Methods
Clinical and pathological data as well as blood samples for extracting DNA were obtained for 73 patients with PDA. Real-time PCR assessed genetic variants of APC (I1307K and E1317Q), and four different single nucleotide polymorphisms (SNPs) in the CD24 gene: C170T (rs52812045), TG1527del (rs3838646), A1626G (rs1058881) and A1056G (rs1058818).Results
The median age at diagnosis was 64 (41–90) years. Thirty-one patients (42.5%) were operable, 16 (22%) had locally advanced disease and 26 (35.5%) had disseminated metastatic cancer. The malignancy-related mortality rate was 84%. Median survival was 14 months (11.25–16.74). Survival was similar for wild-type (WT), heterozygous and homozygous variants of the APC or CD24 genes. The three most frequent CD24 SNP combinations were: heterozygote for A1626G and WT for the rest of the alleles (14% of patients), heterozygote for C170T, A1626G, A1056G and WT for the rest (14% of patients), and heterozygote for C170T, A1056G and WT for the rest (10% of patients). All patients were APC WT. The first two groups were significantly younger at diagnosis than the third group.Conclusions
Specific polymorphisms in the APC and CD24 genes may play a role in pancreatic cancer development. Correlation with survival requires a larger cohort. 相似文献12.
Izabela Nowak Maria Magott-Procelewska Agnieszka Kowal Maciej Miazga Marta Wagner Wanda Niepiek?o-Miniewska Ma?gorzata Kamińska Andrzej Wi?niewski Edyta Majorczyk Marian Klinger Wioleta ?uszczek Andrzej Pawlik Rafa? P?oski Ewa Barcz David Senitzer Piotr Ku?nierczyk 《PloS one》2012,7(9)
Background
Recipient NK cells may detect the lack of recipient''s (i.e., self) HLA antigens on donor renal tissue by means of their killer cell immunoglobulin-like receptors (KIRs). KIR genes are differently distributed in individuals, possibly contributing to differences in response to allogeneic graft.Methodology/Principal Findings
We compared frequencies of 10 KIR genes by PCR-SSP in 93 kidney graft recipients rejecting allogeneic renal transplants with those in 190 recipients accepting grafts and 690 healthy control individuals. HLA matching results were drawn from medical records. We observed associations of both a full-length KIR2DS4 gene and its variant with 22-bp deletion with kidney graft rejection. This effect was modulated by the HLA-B,-DR matching, particularly in recipients who did not have glomerulonephritis but had both forms of KIR2DS4 gene. In contrast, in recipients with glomerulonephritis, HLA compatibility seemed to be much less important for graft rejection than the presence of KIR2DS4 gene. Simultaneous presence of both KIR2DS4 variants strongly increased the probability of rejection. Interestingly, KIR2DS5 seemed to protect the graft in the presence of KIR2DS4fl but in the absence of KIR2DS4del.Conclusions/Significance
Our results suggest a protective role of KIR2DS5 in graft rejection and an association of KIR2DS4 with kidney rejection, particularly in recipients with glomerulonephritis. 相似文献13.
Marco Genchi Paola Prati Nadia Vicari Andrea Manfredini Luciano Sacchi Emanuela Clementi Claudio Bandi Sara Epis Massimo Fabbi 《PloS one》2015,10(8)
Background
Tularemia is a zoonosis caused by the Francisella tularensis, a highly infectious Gram-negative coccobacillus. Due to easy dissemination, multiple routes of infection, high environmental contamination and morbidity and mortality rates, Francisella is considered a potential bioterrorism threat and classified as a category A select agent by the CDC. Tick bites are among the most prevalent modes of transmission, and ticks have been indicated as a possible reservoir, although their reservoir competence has yet to be defined. Tick-borne transmission of F. tularensis was recognized in 1923, and transstadial transmission has been demonstrated in several tick species. Studies on transovarial transmission, however, have reported conflicting results.Objective
The aim of this study was to evaluate the role of ticks as reservoirs for Francisella, assessing the transovarial transmission of F. tularensis subsp. holarctica in ticks, using experimentally-infected females of Dermacentor reticulatus and Ixodes ricinus.Results
Transmission electron microscopy and fluorescence in situ hybridization showed F. tularensis within oocytes. However, cultures and bioassays of eggs and larvae were negative; in addition, microscopy techniques revealed bacterial degeneration/death in the oocytes.Conclusions
These results suggest that bacterial death might occur in oocytes, preventing the transovarial transmission of Francisella. We can speculate that Francisella does not have a defined reservoir, but that rather various biological niches (e.g. ticks, rodents), that allow the bacterium to persist in the environment. Our results, suggesting that ticks are not competent for the bacterium vertical transmission, are congruent with this view. 相似文献14.
Aline Santos Sampaio Ana Gabriela Hounie Kátia Petribú Carolina Cappi Ivanil Morais Homero Vallada Maria Concei??o do Rosário S. Evelyn Stewart Jesen Fargeness Carol Mathews Paul Arnold Gregory L. Hanna Margaret Richter James Kennedy Leonardo Fontenelle Carlos Alberto de Bragan?a Pereira David L. Pauls Eurípedes Constantino Miguel 《PloS one》2015,10(3)
Objective
Obsessive-compulsive disorder (OCD) is a common and debilitating psychiatric illness. Although a genetic component contributes to its etiology, no single gene or mechanism has been identified to the OCD susceptibility. The catechol-O-methyltransferase (COMT) and monoamine oxidase A (MAO-A) genes have been investigated in previous OCD studies, but the results are still unclear. More recently, Taylor (2013) in a comprehensive meta-analysis of genetic association studies has identified COMT and MAO-A polymorphisms involved with OCD. In an effort to clarify the role of these two genes in OCD vulnerability, a family-based association investigation was performed as an alternative strategy to the classical case-control design.Methods
Transmission disequilibrium analyses were performed after genotyping 13 single-nucleotide polymorphisms (eight in COMT and five in MAO-A) in 783 OCD trios (probands and their parents). Four different OCD phenotypes (from narrow to broad OCD definitions) and a SNP x SNP epistasis were also analyzed.Results
OCD, broad and narrow phenotypes,were not associated with any of the investigated COMT and MAO-A polymorphisms. In addition, the analyses of gene-gene interaction did not show significant epistatic influences on phenotype between COMT and MAO-A.Conclusions
The findings do not support an association between DSM-IV OCD and the variants of COMT or MAO-A. However, results from this study cannot exclude the contribution of these genes in the manifestation of OCD. The evaluation of broader spectrum phenotypes could help to understand the role of these and other genes in the pathophysiology of OCD and its spectrum disorders. 相似文献15.
Da Hyun Jung Jie-Hyun Kim Hyun Soo Chung Jun Chul Park Sung Kwan Shin Sang Kil Lee Yong Chan Lee 《PloS one》2015,10(4)
Background
There is controversy about the effect of Helicobacter pylori (H. pylori) eradication on the prevention of metachronous gastric cancer after endoscopic resection (ER).Aims
The aim of this study was to systematically evaluate the effect of H. pylori eradication on the prevention of metachronous gastric lesions after ER of gastric neoplasms.Methods
We performed a systematic search of PubMed, EMBASE, the Cochrane Library, and MEDLINE that encompassed studies through April 2014. Our meta-analysis consisted of 10 studies, which included 5881 patients who underwent ER of gastric neoplasms.Results
When we compared the incidence of metachronous lesions between H. pylori-eradicated and non-eradicated groups, H. pylori eradication significantly lowered the risk of metachronous lesions after ER of gastric neoplasms (five studies, OR = 0.392, 95% CI 0.259 – 0.593, P < 0.001). When we compared H. pylori-eradicated and persistent groups, again, H. pylori eradication significantly lowered the incidence of metachronous lesions after ER of gastric neoplasms (six studies, OR = 0.468, 95% CI 0.326 – 0.673, P < 0.001). There was no obvious heterogeneity across the analyzed studies.Conclusions
This meta-analysis suggests a preventive role for H. pylori eradication for metachronous gastric lesions after ER of gastric neoplasms. Thus, H. pylori eradication should be considered if H. pylori infection is confirmed during ER. 相似文献16.
Shubhashree Uppangala Shilly Dhiman Sujit Raj Salian Vikram Jeet Singh Guruprasad Kalthur Satish Kumar Adiga 《PloS one》2015,10(3)
Background
Concerns regarding the safety of ICSI have been intensified recently due to increased risk of birth defects in ICSI born children. Although fertilization rate is significantly higher in ICSI cycles, studies have failed to demonstrate the benefits of ICSI in improving the pregnancy rate. Poor technical skill, and suboptimal in vitro conditions may account for the ICSI results however, there is no report on the effects of oocyte manipulations on the ICSI outcome.Objective
The present study elucidates the influence of mock ICSI on the functional and genetic integrity of the mouse oocytes.Methods
Reactive Oxygen Species (ROS) level, mitochondrial status, and phosphorylation of H2AX were assessed in the in vivo matured and IVM oocytes subjected to mock ICSI.Results
A significant increase in ROS level was observed in both in vivo matured and IVM oocytes subjected to mock ICSI (P<0.05-0.001) whereas unique mitochondrial distribution pattern was found only in IVM oocytes (P<0.01-0.001). Importantly, differential H2AX phosphorylation was observed in both in vivo matured and IVM oocytes subjected to mock ICSI (P <0.001).Conclusion
The data from this study suggests that mock ICSI can alter genetic and functional integrity in oocytes and IVM oocytes are more vulnerable to mock ICSI induced changes. 相似文献17.
18.
Seung Hwan Shin Da Hyun Jung Jie-Hyun Kim Hyun Soo Chung Jun Chul Park Sung Kwan Shin Sang Kil Lee Yong Chan Lee 《PloS one》2015,10(11)
Purpose
There is insufficient data about the role of eradication of H. pylori after endoscopic resection (ER) for gastric dysplasia. The aim was to investigate the benefit of H. pylori eradication after ER in patients with gastric dysplasia to prevent metachronous gastric neoplasms.Materials and Methods
We retrospectively reviewed 1872 patients who underwent ER of gastric dysplasia. We excluded patients with a follow-up period of <2 years or who had not undergone tests for active H. pylori infection. A total of 282 patients were enrolled. The patients were categorized into those without active H. pylori infection (H. pylori-negative group, n = 124), those who successfully underwent H. pylori eradication (eradicated group, n = 122), and those who failed or did not undergo H. pylori eradication (persistent group, n = 36).Results
Metachronous recurrence was diagnosed in 36 patients, including 19 in the H. pylori-negative group, 10 in the eradicated group, and 7 in the persistent group. The cumulative incidence of metachronous recurrence was significantly lower in the H. pylori-eradicated group in comparison with either of the H. pylori-persistent (non-eradicated or failed) groups (p = 0.039). Similarly, the incidence of metachronous recurrence was significantly lower in the H. pylori-eradicated group compared with the H. pylori-negative group (p = 0.041).Conclusion
Successful H. pylori eradication may reduce the development of metachronous gastric neoplasms after ER in patients with gastric dysplasia. 相似文献19.
Joyce Weeland Meike Slagt Eddie Brummelman Walter Matthys Bram Orobio de Castro Geertjan Overbeek 《PloS one》2015,10(11)
Background
There is increasing evidence that variation in the promoter region of the serotonin transporter gene SLC6A4 (i.e., the 5-HTTLPR polymorphism) moderates the impact of environmental stressors on child psychopathology. Emotional reactivity −the intensity of an individual’s response to other’s emotions− has been put forward as a possible mechanism underlying these gene-by-environment interactions (i.e., G×E). Compared to children homozygous for the L-allele (LL-genotypes), children carrying an S-allele (SS/SL-genotypes), specifically when they have been frequently exposed to negative emotions in the family environment, might be more emotionally reactive and therefore more susceptible to affective environmental stressors. However, the association between 5-HTTLPR and emotional reactivity in children has not yet been empirically tested. Therefore, the goal of this study was to test this association in a large-scale experiment.Methods
Children (N = 521, 52.5% boys, Mage = 9.72 years) were genotyped and randomly assigned to happy, angry or neutral dynamic facial expressions and vocalizations. Motor and affective emotional reactivity were assessed through children’s self-reported negative and positive affect (n = 460) and facial electromyography activity (i.e., fEMG: the zygomaticus or “smile” muscle and the corrugator or “frown” muscle, n = 403). Parents reported on their negative and positive parenting behaviors.Results
Children mimicked and experienced the emotion they were exposed to. However, neither motor reactivity nor affective reactivity to these emotions depended on children’s 5-HTTLPR genotype: SS/SL-genotypes did not manifest any stronger response to emotional stimuli than LL-genotypes. This finding remained the same when taking the broader family environment into account, controlling for kinship, age, gender and genetic ancestry, and when including a tri-allelic factor.Conclusions
We found no evidence for an association between the 5-HTTLPR polymorphism and children’s emotional reactivity. This finding is important, in discounting one potential underlying endophenotype of G×E between the 5-HTTLPR and affective environmental stressors. 相似文献20.
Yasuhiro Maeda Kiyoshi Migita Osamu Higuchi Akihiro Mukaino Hiroshi Furukawa Atsumasa Komori Minoru Nakamura Satoru Hashimoto Shinya Nagaoka Seigo Abiru Hiroshi Yatsuhashi Hidenori Matsuo Atsushi Kawakami Michio Yasunami Shunya Nakane 《PloS one》2016,11(1)