tbuckley/cabot-search huggingface dataset:
Cross-Disorder Genomewide Analysis of Schizophrenia, Bipolar Disorder, and Depression
Authors: Jie Huang, Roy H. Perlis, Phil H. Lee, A. John Rush, Maurizio Fava, Gary S. Sachs, Jeffrey Lieberman, Steven P. Hamilton, Patrick Sullivan, Pamela Sklar, Shaun Purcell, Jordan W. Smoller
Journal: American Journal of Psychiatry (2010)

Family and twin studies indicate substantial overlap of genetic influences on psychotic and mood disorders. Linkage and candidate gene studies have also suggested overlap across schizophrenia, bipolar disorder, and major depressive disorder. The purpose of this study was to apply genomewide association study (GWAS) analysis to address the specificity of genetic effects on these disorders.The authors combined GWAS data from three large effectiveness studies of schizophrenia (CATIE, genotyped: N=741), bipolar disorder (STEP-BD, geno-typed: N=1,575), and major depressive disorder (STAR*D, genotyped: N=1,938) as well as from psychiatrically screened control subjects (NIMH-Genetics Repository: N=1,204). A two-stage analytic procedure involving an omnibus test of allele frequency differences among case and control groups was applied, followed by a model selection step to identify the best-fitting model of allelic effects across disorders.The strongest result was seen for a single nucleotide polymorphism near the adrenomedullin (ADM) gene (rs6484218), with the best-fitting model indicating that the effect was specific to bipolar II disorder. Findings also revealed evidence suggesting that several genes may have effects that transcend clinical diagnostic boundaries, including variants in NPAS3 that showed pleiotropic effects across schizophrenia, bipolar disorder, and major depressive disorder.This study provides the first genomewide significant evidence implicating variants near the ADM gene on chromosome 11p15 in psychopathology, with effects that appear to be specific to bipolar II disorder. Although genomewide significant evidence of cross-disorder effects was not detected, the results provide evidence that there are both pleiotropic and disorder-specific effects on major mental illness and illustrate an approach to dissecting the genetic basis of mood and psychotic disorders that can inform future large-scale cross-disorder GWAS analyses.
Psoriasis vulgaris in Chinese individuals is associated with<i>PSORS1C3</i>and<i>CDSN</i>genes
Authors: Y.T. Chang, C.T. Chou, Y.M. Shiao, M.W. Lin, C.W. Yu, C.C. Chen, C.H. Huang, D.D. Lee, H.N. Liu, W.J. Wang, S.F. Tsai
Journal: British Journal of Dermatology (2006)

Background Besides the HLA‐Cw*0602 allele, the psoriasis susceptibility 1 candidate 3 (PSORS1C3) and corneodesmosin (CDSN) genes are two probable psoriasis susceptibility genes in the PSORS1 locus. The −79C, −26C and +246A alleles of the PSORS1C3 gene, the CDSN*971T allele, CDSN*TTC (619T–1236T–1243C) and CDSN*5 (619T–1240G–1243C) are strongly associated with psoriasis in the caucasian population. Until now, no haplotype study of the PSORS1C3 and CDSN genes has been documented in Chinese patients with psoriasis vulgaris. Objectives We aimed to determine whether genetic polymorphisms of the PSORS1C3 and CDSN genes were associated with an increased risk of psoriasis vulgaris in Chinese patients in Taiwan. Methods We investigated the PSORS1C3 and CDSN genes for disease association by direct sequencing in 178 patients with psoriasis vulgaris and 203 control subjects. Genotyping for HLA‐Cw*0602, α‐helix coiled‐coil rod homologue (HCR) gene and single nucleotide polymorphism (SNP) n.9 was also carried out using a sequence‐based typing method. Results The PSORS1C3*582A allele, an SNP in the 3′‐untranslated region of the PSORS1C3 gene, was a major psoriasis vulgaris susceptibility allele in the Chinese population, and the association was much stronger in patients with early‐onset psoriasis vulgaris (22·3% vs. 6·9%, odds ratio = 3·87, Pc =0·0000072). The frequencies of CDSN*TTC and CDSN*971T were also significantly increased in patients with early‐onset psoriasis vulgaris. Moreover, PSORS1C3*582A, SNP n.9*C, Cw*0602 and HCR*WWCC were in near complete linkage disequilibrium (LD) with each other; in contrast, the LD with the CDSN gene was not so strong. SNP n.9*C–Cw*0602–PSORS1C3*582A–HCR*WWCC was a major susceptibility haplotype in patients with early‐onset psoriasis vulgaris (P < 10−7) and this risk haplotype also carried CDSN*TTC and CDSN*971T. Conclusions The PSORS1C3 and CDSN genes are important psoriasis susceptibility genes in Chinese patients with psoriasis vulgaris.
Modelling the production of nitric oxide within the human airways
Authors: R.A. Jörres
Journal: European Respiratory Journal (2000)

The measurement of exhaled nitric oxide (NO) is well established for monitoring of airway inflammation in bronchial asthma. It is known that the concentration of NO determined as steady state (plateau) value at a constant expiratory flow rate depends on the flow rate chosen. This suggests that the exhaled NO is released within the conducting airways, whereas alveolar NO levels are negligible. The processes involved can be described through a lung model comprising an alveolar compartment and an airway compartment thought of as a pipe. This concept has been formulated mathematically and the models proposed in the literature are essentially equivalent. NO plateau levels obtained at different flow rates allow the estimation of 1) an effective airway wall NO concentration that represents the driving force for NO release, 2) an airway diffusing capacity for NO which depends on factors impeding or facilitating NO transport, including an increase in NO-producing surface area. Clinical studies will have to assess whether the knowledge of these or related parameters offers a significant advantage over the determination of exhaled NO at a single flow rate.
Loss of miR-204 Expression Enhances Glioma Migration and Stem Cell-like Phenotype
Authors: Zhe Ying, Yun Li, Jueheng Wu, Xun Zhu, Yi Yang, Han Tian, Wei Li, Bo Hu, Shi-Yuan Cheng, Mengfeng Li
Journal: Cancer Research (2012)

Abstract Phenotypic similarities have long been recognized between subpopulations of glioma and neural stem cells. Many of these similar properties, including the robust abilities to self-renew, migrate, and invade, are hallmarks of glioma cells that render them extremely aggressive. However, the molecular mechanisms underlying this character, particularly in glioma stem-like cells that drive this disease, remain poorly understood. Here, we report the results of a differential miRNA expression screen that compared glioma and neural stem cells, where we found that miR-204 was markedly downregulated in both types of cells. Mechanistic investigations revealed that miR-204 simultaneously suppressed self-renewal, stem cell-associated phenotype, and migration of glioma cells by targeting the stemness-governing transcriptional factor SOX4 and the migration-promoting receptor EphB2. Restoring miR-204 expression in glioma cells suppressed tumorigenesis and invasiveness in vivo and increased overall host survival. Further evaluation revealed that the miR-204 promoter was hypermethylated and that attenuating promoter methylation was sufficient to upregulate miR-204 in glioma cells. Together, our findings reveal miR-204 as a pivotal regulator of the development of stem cell-like phenotypes and cell motility in malignant glioma cells. Cancer Res; 73(2); 990–9. ©2012 AACR.
Side Population Cells Isolated from Mesenchymal Neoplasms Have Tumor Initiating Potential
Authors: Colleen Wu, Qingxia Wei, Velani Utomo, Puviindran Nadesan, Heather Whetstone, Rita Kandel, Jay S. Wunder, Benjamin A. Alman
Journal: Cancer Research (2007)

Abstract Although many cancers are maintained by tumor-initiating cells, this has not been shown for mesenchymal tumors, in part due to the lack of unique surface markers that identify mesenchymal progenitors. An alternative technique to isolate stem-like cells is to isolate side population (SP) cells based on efflux of Hoechst 33342 dye. We examined 29 mesenchymal tumors ranging from benign to high-grade sarcomas and identified SP cells in all but six samples. There was a positive correlation between the percentage of SP cells and the grade of the tumor. SP cells preferentially formed tumors when grafted into immunodeficient mice, and only cells from tumors that developed from the SP cells had the ability to initiate tumor formation upon serial transplantation. Although SP cells are able to efflux rhodamine dye in addition to Hoechst 33342, we found that the ability to efflux rhodamine dye did not identify a population of cells enriched for tumor-initiating capacity. Here, we identify a subpopulation of cells within a broad range of benign and malignant mesenchymal tumors with tumor-initiating capacity. In addition, our data suggest that the proportion of SP cells could be used as a prognostic factor and that therapeutically targeting this subpopulation of cells could be used to improve patient outcome. [Cancer Res 2007;67(17):8216–22]
Clinical features and risk factors of postsurgical gout
Authors: E H Kang, E Y Lee, Y J Lee, Y W Song, E B Lee
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objectives:</h3> To investigate the clinical characteristics and risk factors of gout attacks that develop during the postsurgical period. <h3>Methods:</h3> We enrolled 67 patients with gout who developed postsurgical gout and 67 controls who had histories of gout but did not develop gout attacks after surgery. Features of the postsurgical gout attacks were analysed and compared to those of presurgical gout attacks suffered by patients and controls. Demographics, medical backgrounds, laboratory data and surgical factors were compared between patients and controls in order to establish risk factors associated with postsurgical gout. <h3>Results:</h3> The mean (SD) time interval to develop postsurgical gout was 4.2 (3.1) days. The attacks tended to involve lower extremity joints (65/67, 97.0%), usually the first metatarsophalangeal joint (42/67, 62.7%), and to affect more than one joint (34/67, 50.7%). The number of attacked joints was positively correlated with the total number of previously involved joints (r = 0.281, p = 0.026). The site of attacks had a preference for the previously affected sites. A history of cancer surgery (p = 0.002), elevated presurgical serum urate levels (⩾9 mg/dl; p = 0.002) and failure to administer colchicine prophylaxis (p = 0.008) were found to be risk factors for postsurgical gout. <h3>Conclusions:</h3> Postsurgical gout tends to develop within 8 days after surgery. The site and number of involved joints reflect the features of gout attacks the patient suffered before surgery. Adequate presurgical control of serum uric acid levels and/or prophylactic administration of colchicine will help prevent gout attacks during the postsurgical period.
Histone Deacetylase Inhibitors Induce a Very Broad, Pleiotropic Anticancer Drug Resistance Phenotype in Acute Myeloid Leukemia Cells by Modulation of Multiple ABC Transporter Genes
Authors: Stefanie Hauswald, Jesus Duque-Afonso, Michaela M. Wagner, Florian M. Schertl, Michael Lübbert, Christian Peschel, Ulrich Keller, Thomas Licht
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Histone deacetylase inhibitors (HDACi) are being studied in clinical trials with the aim to induce cellular differentiation, growth arrest, and apoptosis of tumor cells. Recent reports suggest that the multidrug resistance-1 (MDR1) gene is regulated by epigenetic mechanisms. To investigate whether additional drug transporters are regulated by HDACi and how this affects cytotoxicity, acute myeloid leukemia (AML) cells were examined. Experimental Design: AML cells were cultured in the presence of phenylbutyrate, valproate, suberoylanilide hydroxamic acid, or trichostatin A and analyzed for drug transporter expression and function as well as sensitivity to anticancer drugs. Results: MDR1, breast cancer resistance protein (BCRP), and multidrug resistance-associated proteins (MRP) 7 and 8 were induced in a dose- and time-dependent manner as shown by semiquantitative PCR. The pattern of gene induction was cell line specific. Phenylbutyrate induced P-glycoprotein and BCRP expression and the efflux of drugs as determined with labeled substrates. KG-1a cells treated with phenylbutyrate developed resistance to daunorubicin, mitoxantrone, etoposide, vinblastine, paclitaxel, topotecan, gemcitabine, and 5-fluorouracil; as a result drug-induced apoptosis was impaired. Chromatin immunoprecipitation revealed the hyperacetylation of histone proteins in the promoter regions of MDR1, BCRP, and MRP8 on valproate treatment. Furthermore, an alternative MRP8 promoter was induced by HDACi treatment. Conclusions: Exposure of AML cells to HDACi induces a drug resistance phenotype broader than the “classic multidrug resistance,” which might negatively affect treatment effectiveness.
STUDIES ON VARICELLA
Authors: Thomas M. Rivers, William S. Tillett
Journal: The Journal of Experimental Medicine (1923)

1. The localization of the virus of varicella in the human skin is influenced by irritation. This is indirect evidence that the virus is in the blood. 2. Rabbits are susceptible to a virus recovered from the blood of varicella patients. 3. Testicular emulsions containing the virus are free from ordinary aerobic and anaerobic bacteria, and produce lesions in the cornea, skin, and testicles of rabbits. 4. The virus can be transmitted indefinitely from rabbit to rabbit by means of testicular inoculation, and can be preserved 29 days in 50 per cent glycerol at a low temperature.
Induction of Fc epsilon R2/CD23 on human epidermal Langerhans cells by human recombinant interleukin 4 and gamma interferon.
Authors: T Bieber, A Rieger, C Neuchrist, J C Prinz, E P Rieber, G Boltz-Nitulescu, O Scheiner, D Kraft, J Ring, G Stingl
Journal: The Journal of Experimental Medicine (1989)

Human rIL-4 and human rIFN-gamma are able to induce the expression of the low affinity receptor for IgE (Fc epsilon R2/CD23) on normal human epidermal Langerhans cells, whereas IL-2 and PMA have no effect. A synergistic effect is observed when both cytokines are combined. These receptors are synthesized de novo by the LC since cycloheximide completely inhibits the appearance of Fc epsilon R2/CD23. Fc epsilon R2/CD23+ LC may have a major role in the pathogenesis of atopic eczema, as well as in the regulation of IgE synthesis.
Diagnostic performance of the ACR/EULAR 2010 criteria for rheumatoid arthritis and two diagnostic algorithms in an early arthritis clinic (REACH)
Authors: C. Alves, J. J. Luime, D. van Zeben, A.-M. Huisman, A. E. A. M. Weel, P. J. Barendregt, J. M. W. Hazes
Journal: Annals of the Rheumatic Diseases (2011)

An ACR/EULAR task force released new criteria to classify rheumatoid arthritis at an early stage. This study evaluates the diagnostic performance of these criteria and algorithms by van der Helm and Visser in REACH.Patients with symptoms ≤12 months from REACH were used. Algorithms were tested on discrimination, calibration and diagnostic accuracy of proposed cut-points. Two patient sets were defined to test robustness; undifferentiated arthritis (UA) (n=231) and all patients including those without synovitis (n=513). The outcomes evaluated were methotrexate use and persistent disease at 12 months.In UA patients all algorithms had good areas under the curve 0.79, 95% CI 0.73 to 0.83 for the ACR/EULAR criteria, 0.80, 95% CI 0.74 to 0.87 for van der Helm and 0.83, 95% CI 0.77 to 0.88 for Visser. All calibrated well. Sensitivity and specificity were 0.74 and 0.66 for the ACR/EULAR criteria, 0.1 and 1.0 for van der Helm and 0.59 and 0.93 for Visser. Similar results were found in all patients indicating robustness.The ACR/EULAR 2010 criteria showed good diagnostic properties in an early arthritis cohort reflecting daily practice, as did the van der Helm and Visser algorithms. All were robust. To promote uniformity and comparability the ACR/EULAR 2010 criteria should be used in future diagnostic studies.
Effect of aerobic exercise training on mtDNA deletion in soleus muscle of trained and untrained Wistar rats
Authors: A Jafari, M A Hosseinpourfaizi, M Houshmand, A A Ravasi
Journal: British Journal of Sports Medicine (2005)

According to the theory of mitochondrial aging, oxidative stress plays a major role in aging and age related degenerative diseases. Since oxygen consumption and reactive oxygen species rate increase during aerobic exercise, we hypothesised that heavy aerobic training could lead to enhanced mitochondrial DNA (mtDNA) deletion in postmitotic tissues, leading in turn to premature aging and degenerative diseases.Sixty adult male 2 month old Wistar14848 rats were divided into six equal groups. Two groups were trained for 3 months by running on a treadmill (5 days/week, incline 6 degrees; group 1: 40 m/min, 20 min/day; group 2: 20 m/min, 40 min/day), while two sedentary groups participated in aerobic exercise only at the end of the study (incline 6 degrees; group 3: 40 m/min; group 4: 20 m/min). To control for physical and physiological parameters, two groups of untrained animals were killed at the beginning (group 6) and end (group 5) of the study. Expand long PCR was used to investigate mtDNA deletion in soleus muscle and a sequencing method was used to confirm the mtDNA deletion break point.Our results did not show any mtDNA deletion in untrained rats or in those that underwent moderate training (group 2) We only found mtDNA deletion (4.6 kb) in the soleus muscle of heavily trained rats (group 1).These results demonstrate that one session of aerobic exercise does not cause mtDNA deletion in skeletal muscle. The difference in results between heavy and moderate aerobic training may be due to low work rate or up-regulation of inducible antioxidant systems in moderate training.
Influence of IL-6, COL1A1, and VDR gene polymorphisms on bone mineral density in Crohn's disease
Authors: C E Todhunter
Journal: Gut (2005)

<b>Background:</b> Osteoporosis is an important cause of morbidity in patients with Crohn's disease. The pathogenesis of reduced bone mineral density (BMD) is multifactorial. A range of genetic factors have been implicated in other populations of patients with osteoporosis. <b>Aim:</b> To investigate the influence of interleukin 6 (<i>IL-6</i>), collagen type 1α1 (<i>COL1A1</i>), and vitamin D receptor gene (<i>VDR</i>) single nucleotide polymorphisms (SNP) on BMD in patients with Crohn's disease. <b>Patients:</b> A cohort of 245 well characterised patients with Crohn's disease were recruited from the inflammatory bowel disease register at the Freeman Hospital and Royal Victoria Infirmary, Newcastle upon Tyne, and the Queen Elizabeth Hospital, Gateshead, UK. <b>Methods:</b> Patients were genotyped for <i>IL-6</i> C-174G SNP, <i>COL1A1</i> Sp1 binding site G T SNP, <i>VDR Taq1</i>, and <i>Fok1</i> SNPs, and <i>CARD15</i> R702W, G908R, and L1007fs SNPs. BMD was measured at the lumbar spine (LSP) and hip using dual energy <i>x</i> ray absorptiometry. <b>Results:</b> A total of 158 female and 87 male patients, aged 24–70 years (mean 44), were recruited. There were no significant differences in the distribution of the tested SNPs when analysed for age, body mass index, pre/post-menopausal status, smoking, or steroid use. Two hundred and thirteen patients were genotyped for the <i>IL-6</i> SNP. LSP and total hip BMD was significantly lower in patients with the GG genotype (48%) than the CC genotype (15%) (p = 0.041, p = 0.014). One hundred and eighty patients were genotyped for the <i>COL1A1</i> SNP. There was no significant difference in BMD at LSP. Hip BMD was significantly lower in heterozygous patients compared with homozygous wild-types (p = 0.034). There were no significant differences in BMD between genotypes for the two <i>VDR</i> SNPs or the <i>CARD15</i> genotypes examined. <b>Conclusion:</b><i>IL-6</i> and <i>COL1A1</i> gene polymorphisms influence BMD in patients with Crohn's disease but the particular <i>VDR</i> gene polymorphisms studied do not have a major effect.
Measuring Opportunities to Improve Timeliness of Breast Cancer Care at Dana-Farber/Brigham and Women’s Cancer Center
Authors: Craig A. Bunnell, Katya Losk, Sarah Kadish, Nancy Lin, Judith Hirshfield-Bartek, Linda Cutone, Kristen Camuso, Mehra Golshan, Saul Weingart
Journal: Journal of the National Comprehensive Cancer Network (2014)

The authors sought to measure the timeliness of care for patients with breast cancer at Dana-Farber/Brigham and Women's Cancer Center throughout the treatment continuum, and to identify sources of variation that may serve as targets for improving care delivery. This report describes the methods that were developed to measure and analyze baseline performance.
Ovarian follicle development and transgenic mouse models
Authors: K.R. Barnett, C. Schilling, C.R. Greenfeld, D. Tomic, J.A. Flaws
Journal: Human Reproduction Update (2006)

Ovarian follicle development is a complex process that begins with the establishment of what is thought to be a finite pool of primordial follicles and culminates in either the atretic degradation of the follicle or the release of a mature oocyte for fertilization. This review highlights the many advances made in understanding these events using transgenic mouse models. Specifically, this review describes the ovarian phenotypes of mice with genetic mutations that affect ovarian differentiation, primordial follicle formation, follicular growth, atresia, ovulation and corpus luteum (CL) formation. In addition, this review describes the phenotypes of mice with mutations in a variety of genes, which affect the hormones that regulate folliculogenesis. Because studies using transgenic animals have revealed a variety of reproductive abnormalities that resemble many reproductive disorders in women, it is likely that studies using transgenic mouse models will impact our understanding of ovarian function and fertility in women.
Kinetics of Response to Long-Term Treatment Combining Pentoxifylline and Tocopherol in Patients With Superficial Radiation-Induced Fibrosis
Authors: Sylvie Delanian, Raphaël Porcher, Jérémie Rudant, Jean-Louis Lefaix
Journal: Journal of Clinical Oncology (2005)

Purpose Significant regression of radiation (RT) -induced fibrosis (RIF) has been achieved after treatment combining pentoxifylline (PTX) and alpha-tocopherol (vitE). In this study, we focus on the maximum response, how long it takes to achieve response, and changes after treatment discontinuation. Patients and Methods Measurable superficial RIF was assessed in patients treated by RT for breast cancer in a long-treatment (24 to 48 months) PTX-vitE (LPE) group of 37 patients (47 RIFs) and in a short-treatment (6 to 12 months) PTX-vitE (SPE) group of seven patients (eight RIFs). Between April 1995 and April 2000, women were treated with a daily combination of PTX (800 mg) and VitE (1,000 IU). Results Combined PTX-vitE was continuously effective and resulted in exponential RIF surface area regression (−46% for LPE and −68% for SPE at 6 months, −58% for LPE and −69% for SPE at 12 months, −63% for LPE and −62% for SPE at 18 months, and −68% for LPE at 24 and 36 months). The mean estimated maximal treatment effect was 68% RIF surface area regression. The mean time to this effect was 24 months and was shorter (16 months) in more recent RIF (&lt; 6 years since RT) than in older RIF (28 months; P = .0003). Symptom severity (Subjective Objective Medical Management and Analytic Evaluation score) was halved in both groups. After treatment discontinuation, mean RIF surface area at 1 year had increased by +40% in the SPE group (rebound) and +8.5% in the LPE group. Conclusion Under combined PTX-vitE treatment, RIF regression was exponential, with a two-thirds maximum response after a mean of 2 years. There was a risk of a rebound effect if treatment was too short. Long treatment (≥ 3 years) is recommended in patients with severe RIF.