tbuckley/cabot-search huggingface dataset:
Positive association between<i>STAT4</i>polymorphisms and polymyositis/dermatomyositis in a Japanese population
Authors: Tomoko Sugiura, Yasushi Kawaguchi, Kanako Goto, Yukiko Hayashi, Rie Tsuburaya, Takefumi Furuya, Takahisa Gono, Ichizo Nishino, Hisashi Yamanaka
Journal: Annals of the Rheumatic Diseases (2012)

To investigate associations between signal transducer and activator of transcription 4 (STAT4), one of the most commonly acknowledged genes for the risk of multiple autoimmune diseases, with susceptibility to adult-onset polymyositis/dermatomyositis among Japanese individuals.A single nucleotide polymorphism of STAT4, rs7574865, was genotyped using TaqMan assay in 1143 Japanese individuals. The first set comprised 138 polymyositis/dermatomyositis patients and 289 controls and the second set comprised 322 patients and 394 controls. 460 patients (273 polymyositis and 187 dermatomyositis patients) and 683 controls were genotyped.rs7574865T conferred a risk of polymyositis/dermatomyositis with an OR of 1.37 (95% CI 1.16 to 1.64; p=4x10(-4); p(corr)=0.0012). Both polymyositis and dermatomyositis exhibited high associations with the rs7574865T allele (polymyositis: OR=1.36, 95% CI 1.11 to 1.67; p=0.0039; p(corr)=0.012; dermatomyositis: OR=1.40, 95% CI 1.10 to 1.78; p=0.0054; p(corr)=0.016). The association between this STAT4 polymorphism and interstitial lung disease (ILD) was also investigated in the first set of polymyositis/dermatomyositis patients (n=138); those with ILD (n=79) bore rs7574865T more frequently compared with controls (OR 1.59, 95% CI 1.10 to 2.28; p=0.013; p(corr)=0.039).This is the first study to show a positive association between a STAT4 polymorphism and polymyositis/dermatomyositis, suggesting that polymyositis/dermatomyositis shares a gene commonly associated with the risk of other autoimmune diseases.
Activation of DNA Methyltransferase 1 by EBV Latent Membrane Protein 2A Leads to Promoter Hypermethylation of <i>PTEN</i> Gene in Gastric Carcinoma
Authors: Rumi Hino, Hiroshi Uozaki, Noriko Murakami, Tetsuo Ushiku, Aya Shinozaki, Shumpei Ishikawa, Teppei Morikawa, Takeo Nakaya, Takashi Sakatani, Kenzo Takada, Masashi Fukayama
Journal: Cancer Research (2009)

Abstract CpG island promoter methylation of tumor suppressor genes is one of the most characteristic abnormalities in EBV-associated gastric carcinoma (GC). Aberrant promoter methylation and expression loss of PTEN were evaluated in cancer tissues of GC by methylation-specific PCR and immunohistochemistry, respectively, showing that both abnormalities occurred concurrently in EBV-associated GC. PTEN abnormalities were reiterated in GC cell lines MKN-1 and MKN-7 infected with recombinant EBV, and DNA methyltransferase 1 (DNMT1) was commonly overexpressed in both cell lines. Stable and transient transfection systems in MKN-1 similarly showed that viral latent membrane protein 2A (LMP2A) up-regulated DNMT1, leading to an increase in methylation of the PTEN promoter. Importantly, the level of phosphorylated signal transducer and activator of transcription 3 (pSTAT3) increased in the nuclei of LMP2A-expressing GC cells, and knockdown of STAT3 counteracted LMP2A-mediated DNMT1 overexpression. Immunohistochemistry for both pSTAT3 and DNMT1 showed diffuse labeling in the nuclei of the cancer cells in GC tissues, especially in EBV-associated GC. Taken together, LMP2A induces the phosphorylation of STAT3, which activates DNMT1 transcription and causes PTEN expression loss through CpG island methylation of the PTEN promoter in EBV-associated GC. LMP2A plays an essential role in the epigenetic abnormalities in host stomach cells and in the development and maintenance of EBV-associated cancer. [Cancer Res 2009;69(7):2766–74]
<b><i>ICAM-2</i></b>Gene Therapy for Peritoneal Dissemination of Scirrhous Gastric Carcinoma
Authors: Hiroaki Tanaka, Masakazu Yashiro, Takeshi Sunami, Yoji Sakate, Kinshi Kosaka, Kosei Hirakawa
Journal: Clinical Cancer Research (2004)

Human scirrhous gastric carcinoma develops peritoneal dissemination with high frequency, and the prognosis of patients with peritoneal metastasis is poor. There have been few reports of an immunogene therapy for peritoneal dissemination. Intercellular adhesion molecule (ICAM)-2 is a second ligand of leukocyte function-associated antigen-1, which functions as a costimulatory molecule for effector cells. In the present study, we examined whether ICAM-2 transfection using adenovirus vector is effective gene therapy for peritoneal metastasis of gastric cancer.We constructed an adenovirus vector, AdICAM-2, that encodes the full-length human ICAM-2 gene under control of the cytomegalovirus promoter. This vector expresses high levels of ICAM-2 on the human gastric cancer cell line OCUM-2MD3, which has high peritoneal metastatic ability in nude mice. We investigated the antitumor effects of gene transfer of ICAM-2 using the adenovirus vector AdICAM-2 in vitro and in vivo.ICAM-2 expressed on OCUM-2MD3 cells by AdICAM-2 demonstrated significantly high adhesiveness to and cytotoxicity against peripheral blood mononuclear cells in vitro compared with the control adenovirus vector AdlacZ. Intratumoral injection of AdICAM-2 significantly inhibited the growth of s.c. tumor. Mice with peritoneal metastasis survived for a significantly longer time after AdICAM-2 injection, compared with injection of AdlacZ. Histopathological findings revealed that many natural killer cells infiltrated the peritoneal metastatic lesions after AdICAM-2 injection.These findings suggest that transduction of ICAM-2 into cancer cells enhances the adhesion and activation of natural killer cells, resulting in a reduction of peritoneal metastasis. ICAM-2 transfection using adenovirus vector might be an effective form of gene therapy for peritoneal metastasis of gastric cancer.
Chromosomes of Some Heterotransplanted Human Tumors. II. H.Ep. #1, H.Ep. #3, and H.Ep. #52
Authors: Charles P. Miles, Frank O'Neill
Journal: JNCI Journal of the National Cancer Institute (1965)

Three human epidermoid carcinomas, H.Ep. #1, H.Ep. #3, and H.Ep. #5, have been carried exclusively in rodent heterotransplant passage for periods ranging from 7 to 12 years. All show occasional karyotype variants and mitotic abnormalities, but the rate of variation differs markedly. The stemline Icaryotype of H.Ep. #1 with 59 chromosomes did not vary during a 1-year period. H.Ep. #3 had two stemline karyotypes with 66 and 67 chromosomes when first examined. Six months later two distinct new karyotypes predominated. H.Ep. #5 had a stemline karyotype with 70 chromosomes when first examined. Eight months later cells with a similar karyotype could still be found. In addition, many cells with distinctive markers, dicentrics, a ring, and fragments could be identified.
Homocysteine modulates the effect of simvastatin on expression of ApoA-I and NF- B/iNOS
Authors: L. G. Mikael, R. Rozen
Journal: Cardiovascular Research (2008)

AimsStatins can ameliorate atherosclerosis by inhibition of cholesterol biosynthesis or by modulation of inflammation. In earlier work, we showed that homocysteine (Hcy) reduced synthesis of apolipoprotein A-I (ApoA-I). Our goal in this study was to determine whether Hcy could interfere with the ability of simvastatin to increase ApoA-I synthesis or to modify statin-dependent regulation of inflammatory factors.
The histone deacetylase Rpd3p is required for transient changes in genomic expression in response to stress
Authors: Adriana L Alejandro-Osorio, Dana J Huebert, Dominic T Porcaro, Megan E Sonntag, Songdet Nillasithanukroh, Jessica L Will, Audrey P Gasch
Journal: Genome biology (2009)

Yeast responding to stress activate a large gene expression program called the Environmental Stress Response that consists of approximately 600 repressed genes and approximately 300 induced genes. Numerous factors are implicated in regulating subsets of Environmental Stress Response genes; however, a complete picture of Environmental Stress Response regulation remains unclear. We investigated the role of the histone deacetylase Rpd3p, previously linked to the upstream regions of many Environmental Stress Response genes, in producing Environmental Stress Response gene expression changes in response to stress. We found that the Rpd3-Large complex is required for proper expression of both induced and repressed Environmental Stress Response genes under multiple stress conditions. Cells lacking RPD3 or the Rpd3-Large subunit PHO23 had a major defect in Environmental Stress Response initiation, particularly during the transient phase of expression immediately after stress exposure. Chromatin-immunoprecipitation showed a direct role for Rpd3-Large at representative genes; however, there were different effects on nucleosome occupancy and histone deacetylation at different promoters. Computational analysis implicated regulators that may act with Rpd3p at Environmental Stress Response genes. We provide genetic and biochemical evidence that Rpd3p is required for binding and action of the stress-activated transcription factor Msn2p, although the contribution of these factors differs for different genes. Our results implicate Rpd3p as an important co-factor in the Environmental Stress Response regulatory network, and suggest the importance of histone modification in producing transient changes in gene expression triggered by stress.
Gene Expression Profiling Revealed Survivin as a Target of 3,3′-Diindolylmethane-Induced Cell Growth Inhibition and Apoptosis in Breast Cancer Cells
Authors: KM Wahidur Rahman, Yiwei Li, Zhiwei Wang, Sarah H. Sarkar, Fazlul H. Sarkar
Journal: Cancer Research (2006)

Abstract The phytochemical indole-3-carbinol (I3C), found in cruciferous vegetables, and its major acid-catalyzed reaction product 3,3′-diindolylmethane (DIM) showed anticancer activity mediated by its pleiotropic effects on cell cycle progression, apoptosis, carcinogen bioactivation, and DNA repair. To further elucidate the molecular mechanism(s) by which 3,3′-diindolylmethane exerts its effects on breast cancer cells, we have used microarray gene expression profiling analysis. We found a total of 1,238 genes altered in 3,3′-diindolylmethane-treated cells, among which 550 genes were down-regulated and 688 genes were up-regulated. Clustering analysis showed significant alterations in some genes that are critically involved in the regulation of cell growth, cell cycle, apoptosis, and signal transduction, including down-regulation of survivin. Previous studies have shown that antiapoptotic protein survivin is overexpressed in many human cancers, including breast cancer. However, very little or no information is available regarding the consequence of down-regulation of survivin for cancer therapy. We, therefore, hypothesized that down-regulation of survivin as observed by 3,3′-diindolylmethane could be an important approach for the treatment of breast cancer. We have tested our hypothesis using multiple molecular approaches and found that 3,3′-diindolylmethane inhibited cell growth and induced apoptosis in MDA-MB-231 breast cancer cells by down-regulating survivin, Bcl-2, and cdc25A expression and also caused up-regulation of p21WAF1 expression, which could be responsible for cell cycle arrest. Down-regulation of survivin by small interfering RNA before 3,3′-diindolylmethane treatment resulted in enhanced cell growth inhibition and apoptosis, whereas overexpression of survivin by cDNA transfection abrogated 3,3′-diindolylmethane-induced cell growth inhibition and apoptosis. These results suggest that targeting survivin by 3,3′-diindolylmethane could be a new and novel approach for the prevention and/or treatment of breast cancer. (Cancer Res 2006; 66(9): 4952-60)
Hepatitis b virus replication in acute hepatitis B, acute hepatitis B virus-hepatitis delta virus coinfection and acute hepatitis delta superinfection
Authors: J. Genesca, R. Jardi, M. Buti, L. Vives, S. Prat, J. I. Esteban, R. Esteban, J. Guardia
Journal: Hepatology (1987)

To evaluate the effect of hepatitis delta virus on the level of replication of hepatitis B virus and to assess the clinical significance that such an effect might have on the final outcome of the infection, the serological profile of hepatitis B virus DNA was investigated in 153 patients with acute or chronic hepatitis B virus infection with or without associated delta infection. Serum hepatitis B virus DNA was detected in 57% of patients with acute hepatitis B, 67% of those with acute hepatitis B virus-hepatitis delta virus coinfection and 25% of HBsAg carriers with hepatitis delta virus superinfection during the first week after the onset of symptoms. Patients with acute hepatitis B and those with acute hepatitis B virus-hepatitis delta virus coinfection did not differ significantly with respect to the serological profile of hepatitis B virus DNA and final clinical outcome. Within the group of HBsAg carriers with hepatitis delta virus superinfection, all patients who were initially negative for hepatitis B virus DNA developed chronic hepatitis delta virus infection, whereas 3 of the 4 patients with active hepatitis B virus infection at the time of superinfection showed transient inhibition of hepatitis B virus replication followed by termination of hepatitis delta virus infection in two patients. Therefore, although delta virus may inhibit the replication of hepatitis B virus among chronic HBsAg carriers, this effect is not readily apparent among patients with hepatitis B virus-hepatitis delta virus coinfection.
Promotion of rapid testing for HIV in primary care (RHIVA2): a cluster-randomised controlled trial
Authors: Werner Leber, Heather McMullen, Jane Anderson, Nadine Marlin, Andreia C Santos, Stephen Bremner, Kambiz Boomla, Sally Kerry, Danna Millett, Sifiso Mguni, Sarah Creighton, Jose Figueroa, Richard Ashcroft, Graham Hart, Valerie Delpech, Alison Brown, Graeme Rooney, Maria Sampson, Adrian Martineau, Fern Terris-Prestholt, Chris Griffiths
Journal: The Lancet HIV (2015)
Estrogen Replacement Therapy and Risk of Fatal Colon Cancer in a Prospective Cohort of Postmenopausal Women
Authors: E. E. Calle, H. L. Miracle-McMahill, M. J. Thun, C. W. Heath
Journal: JNCI Journal of the National Cancer Institute (1995)

The results of several recent epidemiologic studies suggest that estrogen replacement therapy (ERT) in postmenopausal women may decrease their risk of subsequently developing colon or colorectal cancer. However, the association is not clear, as other similar studies have failed to show this inverse relationship. Purpose: The present study attempts a more definitive analysis of the relationship between fatal colon cancer and use of ERT among women in a large prospective study of adults in the United States. Women were selected for study from the 676526 female participants in Cancer Prevention Study II (CPS-II), a prospective mortality study of about 1.2 million American men and women (from all 50 states, the District of Columbia, and Puerto Rico), begun by the American Cancer Society in 1982. The median age of the female CPS-II Participants was 56 years in 1982. Vital status was determined through December 31, 1989; 630585 participants (93.2%) were still alive and 43862 (6.5%) had died after 7 years of follow-up. Death certificates were obtained for 96.2% of participants known to have died. At the end of follow-up, 897 colon cancer deaths were observed in a cohort of 422373 postmenopausal women who were cancer free at study entry. Cox proportional hazards modeling was used to compute rate ratios (RRs) and to adjust for other potential risk factors. The likelihood ratio test (two-sided) was used to determine the statistical significance of the interaction terms. Ever use of ERT was associated with significantly decreased risk of fatal colon cancer (RR = 0.71; 95% confidence interval (CI) = 0.61–0.83). The reduction in risk was strongest among current users (RR = 0.55; 95% CI = 0.40–0.76), and there was a significant (P =.0001) trend of decreasing risk with increasing years of use among all users: Users of 1 year or less had an RR of 0.81 (95% CI = 0.63–1.03), while users of 11 years or more had an RR of 0.54 (95% CI = 0.39–0.76). These associations were not altered in multivariate analyses controlling for other risk factors. In our data, estrogen therapy, particularly recent and long-term use, was associated with a substantial decrease in risk of fatal colon cancer. These results were consistent with several published studies suggesting a protective role of exogenous estrogens in the development of colorectal cancer and merit further investigation. (J Natl Cancer Inst 87: 517–523, 1995)
Effect of oral nimodipine on cerebral infarction and outcome after subarachnoid haemorrhage: British aneurysm nimodipine trial.
Authors: J. D. Pickard, G. D. Murray, R. Illingworth, M. D. Shaw, G. M. Teasdale, P. M. Foy, P. R. Humphrey, D. A. Lang, R. Nelson, P. Richards
Journal: BMJ (1989)

OBJECTIVE--To determine the efficacy of oral nimodipine in reducing cerebral infarction and poor outcomes (death and severe disability) after subarachnoid haemorrhage. DESIGN--Double blind, placebo controlled, randomised trial with three months of follow up and intention to treat analysis. To have an 80% chance with a significance level of 0.05 of detecting a 50% reduction in an incidence of cerebral infarction of 15% a minimum of 540 patients was required. SETTING--Four regional neurosurgical units in the United Kingdom. PATIENTS--In all 554 patients were recruited between June 1985 and September 1987 out of a population of 1115 patients admitted with subarachnoid haemorrhage proved by the results of lumbar puncture or computed tomography, or both. The main exclusion criterion was admission to the neurosurgical units more than 96 hours after subarachnoid haemorrhage. There were four breaks of code and no exclusions after entry. One patient was withdrawn and in 130 treatment was discontinued early. All patients were followed up for three months and were included in the analysis, except the patient who had been withdrawn. INTERVENTIONS--Placebo or nimodipine 60 mg was given orally every four hours for 21 days to 276 and 278 patients, respectively. Treatment was started within 96 hours after subarachnoid haemorrhage. END POINTS--Incidence of cerebral infarction and ischaemic neurological deficits and outcome three months after entry. MEASUREMENTS--Demographic and clinical data, including age, sex, history of hypertension and subarachnoid haemorrhage, severity of haemorrhage according to an adaptation of the Glasgow coma scale, number and site of aneurysms on angiography, and initial findings on computed tomography were measured at entry. Deterioration, defined as development of a focal sign or fall of more than one point on the Glasgow coma scale for more than six hours, was investigated by using clinical criteria and by computed tomography, by lumbar puncture, or at necropsy when appropriate. All episodes of deterioration and all patients with a three month outcome other than a good recovery were assessed by a review committee. MAIN RESULTS--Demographic and clinical data at entry were similar in the two groups. In patients given nimodipine the incidence of cerebral infarction was 22% (61/278) compared with 33% (92/276) in those given placebo, a significant reduction of 34% (95% confidence interval 13 to 50%). Poor outcomes were also significantly reduced by 40% (95% confidence interval 20 to 55%) with nimodipine (20% (55/278) in patients given nimodipine v 33% (91/278) in those given placebo). CONCLUSIONS--Oral nimodipine 60 mg four hourly is well tolerated and reduces cerebral infarction snd improves outcome after subarachnoid haemorrhage.
Gene Loss and Evolutionary Rates Following Whole-Genome Duplication in Teleost Fishes
Authors: Frédéric G. Brunet, Hugues Roest Crollius, Mathilde Paris, Jean-Marc Aury, Patricia Gibert, Olivier Jaillon, Vincent Laudet, Marc Robinson-Rechavi
Journal: Molecular Biology and Evolution (2006)

Teleost fishes provide the first unambiguous support for ancient whole-genome duplication in an animal lineage. Studies in yeast or plants have shown that the effects of such duplications can be mediated by a complex pattern of gene retention and changes in evolutionary pressure. To explore such patterns in fishes, we have determined by phylogenetic analysis the evolutionary origin of 675 Tetraodon duplicated genes assigned to chromosomes, using additional data from other species of actinopterygian fishes. The subset of genes, which was retained in double after the genome duplication, is enriched in development, signaling, behavior, and regulation functional categories. The evolutionary rate of duplicate fish genes appears to be determined by 3 forces: 1) fish proteins evolve faster than mammalian orthologs; 2) the genes kept in double after genome duplication represent the subset under strongest purifying selection; and 3) following duplication, there is an asymmetric acceleration of evolutionary rate in one of the paralogs. These results show that similar mechanisms are at work in fishes as in yeast or plants and provide a framework for future investigation of the consequences of duplication in fishes and other animals.
U.S. Hospitalizations for Pneumonia after a Decade of Pneumococcal Vaccination
Authors: Marie R. Griffin, Yuwei Zhu, Matthew R. Moore, Cynthia G. Whitney, Carlos G. Grijalva
Journal: New England Journal of Medicine (2013)

The introduction of 7-valent pneumococcal conjugate vaccine (PCV7) into the U.S. childhood immunization schedule in 2000 has substantially reduced the incidence of vaccine-serotype invasive pneumococcal disease in young children and in unvaccinated older children and adults. By 2004, hospitalizations associated with pneumonia from any cause had also declined markedly among young children. Because of concerns about increases in disease caused by nonvaccine serotypes, we wanted to determine whether the reduction in pneumonia-related hospitalizations among young children had been sustained through 2009 and whether such hospitalizations in older age groups had also declined.
Gas exchange and ventilation–perfusion relationships in the lung
Authors: Johan Petersson, Robb W. Glenny
Journal: European Respiratory Journal (2014)

This review provides an overview of the relationship between ventilation/perfusion ratios and gas exchange in the lung, emphasising basic concepts and relating them to clinical scenarios. For each gas exchanging unit, the alveolar and effluent blood partial pressures of oxygen and carbon dioxide ( P O 2 and P CO 2 ) are determined by the ratio of alveolar ventilation to blood flow ( V ′ A /Q ′) for each unit. Shunt and low V ′ A /Q ′ regions are two examples of V ′ A /Q ′ mismatch and are the most frequent causes of hypoxaemia. Diffusion limitation, hypoventilation and low inspired P O 2 cause hypoxaemia, even in the absence of V ′ A /Q ′ mismatch. In contrast to other causes, hypoxaemia due to shunt responds poorly to supplemental oxygen. Gas exchanging units with little or no blood flow (high V ′ A /Q ′ regions) result in alveolar dead space and increased wasted ventilation, i.e. less efficient carbon dioxide removal. Because of the respiratory drive to maintain a normal arterial P CO 2 , the most frequent result of wasted ventilation is increased minute ventilation and work of breathing, not hypercapnia. Calculations of alveolar–arterial oxygen tension difference, venous admixture and wasted ventilation provide quantitative estimates of the effect of V ′ A /Q ′ mismatch on gas exchange. The types of V ′ A /Q ′ mismatch causing impaired gas exchange vary characteristically with different lung diseases.