tbuckley/cabot-search huggingface dataset:
Responders to cyclophosphamide: results of a single-centre analysis among systemic sclerosis patients
Authors: MO Becker, A Schohe, K Weinert, D Huscher, U Schneider, GR Burmester, G Riemekasten
Journal: Annals of the Rheumatic Diseases (2012)

Interstitial lung fibrosis significantly contributes to morbidity and mortality in systemic sclerosis (SSc),1 but only a few established treatment options exist.2 Cyclophosphamide (CYC)3 is one of the effective options for interstitial lung disease and skin thickening.4 5 However, not all patients respond to this medication and based on the clinical routine practice in one centre, there has been no analysis using reduced intravenous cyclophosphamide (800–1200 mg monthly). 6,–,8 Therefore, we evaluated the response to intravenous cyclophosphamide treatment in 39 patients with SSc in our department. Responders were defined by any of the three outcome parameters: the modified Rodnan skin score (mRSS; responders: decrease by ≥5/51 points), forced vital capacity (FVC; responders: increase or no decline >10%) or diffusing lung capacity for carbon monoxide (DLCO; responders: increase or no decline >10%). Lung function test (LFT) denominated responders that fulfilled both …
Six-month controlled study of effect of desoximetasone and betamethasone 17-valerate on the pituitary-adrenal axis
Authors: ROGER C. CORNELL, RICHARD B. STOUGHTON
Journal: British Journal of Dermatology (1981)

Twenty-two patients were treated with desoximetasone emollient cream 0.25% twice daily without occlusion for 6 months. Patients applied the medication to approximately one-third of their body over psoriatic lesions. Corticosteroid plasma cortisol values decreased to below normal limits in nine patients before the 6-month study was terminated. In four of these the plasma cortisol spontaneously returned to normal despite therapy; in four other patients, however, the plasma cortisol was still suppressed at the end of 5 months of continual therapy but returned to normal within 7 days of discontinuation of the medication. In one patient, lost to further follow-up at 51/2 months of therapy, the trend at the fourth month was an increase in plasma cortisol to within one unit of normal range. Betamethasone 17-valerate 0.1% cream applied twice daily did not suppress plasma cortisol in twenty-three patients similarly tested. The clinical response to desoximetasone emollient cream was significantly better than to betamethasone valerate cream. This study closely approximates the way in which many patients with steroid-responsive dermatoses use potent topical steroids, namely over a long time period and without occlusion.
Allergy and immunity to fungal infections and colonization
Authors: R. Crameri, K. Blaser
Journal: European Respiratory Journal (2002)

Innate and cell-mediated immunity are considered as the principal defence lines against fungal infections in humans. Most opportunistic mycoses occur in individuals with defective innate and/or adaptive cellular immunity. The morbidity and mortality rates associated with infections caused by fungal pathogens are high, and prevention, diagnosis and treatment of these infections remain quite difficult. A variety of pathological conditions, including impaired immune function, are believed to cause host susceptibility to fungal infections as well as to determine the severity and characteristics of the associated pathology. Nonspecific cellular immunity, mediated by macrophages, neutrophils and natural killer cells, provides efficient protection against fungal infections in healthy individuals. A major reason for the increase in systemic mycoses is undoubtedly related to an increased number of patients with congenital or acquired immunodeficiencies. However, there is increasing clinical and experimental evidence indicating that antigen-specific cellular immunity may also play a critical role in host protection against fungi. A better understanding of reciprocal regulation between innate, humoral and adaptive immune responses in the development of an optimal antifungal immunity and, in particular, the improved definition of fungal antigens, may lead to a clarification of the mechanisms involved in host immunity to fungal infections. Molecular cloning and characterization of fungal antigens reveals the involvement of related cross-reactive molecular structures produced by different fungi as pathological molecules involved in development of allergic reactions.
The acute effect of cigarette smoking on the neutrophil elastase inhibitory capacity of peripheral lung lavage from asymptomatic volunteers
Authors: TD Tetley, SF Smith, AJ Winning, JM Foxall, NT Cooke, GH Burton, E Harris, A Guz
Journal: European Respiratory Journal (1989)

Cigarette smoke-induced emphysema is thought to involve reduction of antielastolytic capacity, resulting in elevated elastase activity and lung tissue damage. Peripheral lavage collected from ten asymptomatic subjects immediately before and 20 min after smoking two high tar cigarettes was analysed for neutrophil elastase (NE) inhibitory capacity (IC), alpha 1-proteinase inhibitor (PI) function, elastolytic activity and immunoreactive levels of PI and bronchial inhibitor (BI). The only change found was a small fall in mol immunoreactive PI/mol albumin after smoking (approximately 17%, p less than 0.05) which did not affect NEIC, since PI contributed less than 50% of the NEIC. There was often more NEIC than mol BI + functional PI, suggesting the presence of other NE inhibitors. Thoracic computerized tomography scans of eight of these subjects highlighted two with emphysematous regions of lung; lavage from these two subjects contained either undetectable BI or inactive BI and this suggests a protective role for BI in emphysema.
Selective Protective Effect of Butylated Hydroxytoluene Against 1,2-Dimethylhydrazine Carcinogenesis in BALB/c Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: N K Clapp, N D Bowles, L C Satterfield, W C Klima
Journal: JNCI Journal of the National Cancer Institute (1979)

The effect of the antioxidant butylated hydroxytoluene (BHT) was determined in 1,2-dimethylhydrazine (DMH) colon carcinogenesis. The following groups were comprised of female and male BALB/c mice that were either 1) given BHT (0.75% in the feed) for life beginning at 8 weeks of age, 2) inoculated with DMH (20 mg/kg body wt) sc for 10 weeks beginning at 11 weeks of age, 3) treated with BHT plus DMH, or 4) maintained as untreated controls. Mice of both sexes treated with BHT plus DMH had increased survival over those given DMH alone (females: 93 vs. 64%, P = 0.011; males: 92 vs. 57%, P<0.001). Adenomas and adenocarcinomas were induced by DMH primarily in the descending colon and rectum in both sexes; tumor incidences were reduced in male mice given BHT plus DMH compared with the incidence in males treated with DMH (34 vs. 75%, P=0.0036), but not in females (60 vs. 50%). The numbers of tumors per tumor-bearing mouse were reduced in both sexes given BHT plus DMH as compared with mice given DMH alone (≈2.0 to ≈1.0). Neither BHT-treated mice nor untreated controls had colon or rectal tumors. DMH induced lung tumors, but BHT did not; tumor incidences in mice treated with BHT plus DMH were intermediate between those in mice given DMH or BHT alone. The sex-specific protective effect of BHT on the survival of mice treated with DMH and on the tumor incidences in the large bowel (males only) resembled the sex-specific effect of BHT on diethylnitrosamine-induced squamous cell tumors of the forestomach (females only), but the mechanisms remain unexplained and may be quite different.
Toxic-Shock Syndrome in Menstruating Women
Authors: Kathryn N. Shands, George P. Schmid, Bruce B. Dan, Deborah Blum, Richard J. Guidotti, Nancy T. Hargrett, Roger L. Anderson, Dianne L. Hill, Claire V. Broome, Jeffrey D. Band, David W. Fraser
Journal: New England Journal of Medicine (1980)

To determine the risk factors associated with toxic-shock syndrome (TSS) in menstruating women, we conducted a retrospective telephone study of 52 cases and 52 age-matched and sex-matched controls. Fifty-two cases and 44 controls used tampons (P<0.02). Moreover, in case–control pairs in which both women used tampons, cases were more likely than controls to use tampons throughout menstruation (42 of 44 vs. 34 of 44, respectively; P<0.05). There were no significant differences in brand of tampon used, degree of absorbency specified on label, frequency of tampon change, type of contraceptive used, frequency of sexual intercourse, or sexual intercourse during menstruation. Fourteen of 44 cases had one or more definite or probable recurrences during a subsequent menstrual period. In a separate study, Staphylococcus aureus was isolated from 62 of 64 women with TSS and from seven of 71 vaginal cultures obtained from healthy controls (P<0.001). (N Engl J Med. 1980; 303:1436–42.)
Treatment-by-Histology Interaction Analyses in Three Phase III Trials Show Superiority of Pemetrexed in Nonsquamous Non-small Cell Lung Cancer
Authors: Giorgio Scagliotti, Thomas Brodowicz, Frances A. Shepherd, Christoph Zielinski, Johan Vansteenkiste, Christian Manegold, Lorinda Simms, Frank Fossella, Katherine Sugarman, Chandra P. Belani
Journal: Journal of Thoracic Oncology (2010)
Reversible tumor growth acceleration following bevacizumab interruption in metastatic colorectal cancer patients scheduled for surgery
Authors: W. Cacheux, T. Boisserie, L. Staudacher, O. Vignaux, B. Dousset, O. Soubrane, B. Terris, C. Mateus, S. Chaussade, F. Goldwasser
Journal: Annals of Oncology (2008)
Components of the Cell Death Machine and Drug Sensitivity of the National Cancer Institute Cell Line Panel
Authors: Phyllis A. Svingen, David Loegering, Joe Rodriquez, Xue Wei Meng, Peter W. Mesner, Susan Holbeck, Anne Monks, Stan Krajewski, Dominic A. Scudiero, Edward A. Sausville, John C. Reed, Yuri A. Lazebnik, Scott H. Kaufmann
Journal: Clinical Cancer Research (2004)

Abstract Purpose: According to some studies, susceptibility of cells to anticancer drug-induced apoptosis is markedly inhibited by targeted deletion of genes encoding apoptotic protease activating factor 1 (Apaf-1) or certain caspases. Information about levels of these polypeptides in common cancer cell types and any possible correlation with drug sensitivity in the absence of gene deletion is currently fragmentary. Experimental Design: Immunoblotting was used to estimate levels of Apaf-1 as well as procaspase-2, -3, -6, -7, -8, and -9 in the 60-cell-line panel used for drug screening by the National Cancer Institute. Sensitivity of the same lines to &amp;gt;80,000 compounds was determined with 48-hour sulforhodamine B binding assays. Additional 6-day assays were performed for selected agents. Results: Levels of Apaf-1 and procaspases varied widely. Apaf-1 and procaspase-9, which are implicated in caspase activation after treatment of cells with various anticancer drugs, were detectable in all of the cell lines, with levels of Apaf-1 ranging from ∼1 × 105 to 2 × 106 molecules per cell and procaspase-9 from ∼5 × 103 to ∼1.6 × 105 molecules per cell. Procaspase-8 levels ranged from 1.7 × 105 to 8 × 106 molecules per cell. Procaspase-3, a major effector caspase, varied from undetectable to ∼1.6 × 106 molecules per cell. Correlations between levels of these polypeptides and sensitivity to any of a variety of experimental or conventional antineoplastic agents in either 2-day or 6-day cytotoxicity assays were weak at best. Conclusions: With the exception of caspase-3, all of the components of the core cell-death machinery are expressed in all of the cell lines examined. Despite variations in expression, levels of any one component are not a major determinant of drug sensitivity in these cells in vitro.
Kidney stone disease
Authors: F. L. Coe
Journal: Journal of Clinical Investigation (2005)

About 5% of American women and 12% of men will develop a kidney stone at some time in their life, and prevalence has been rising in both sexes. Approximately 80% of stones are composed of calcium oxalate (CaOx) and calcium phosphate (CaP); 10% of struvite (magnesium ammonium phosphate produced during infection with bacteria that possess the enzyme urease), 9% of uric acid (UA); and the remaining 1% are composed of cystine or ammonium acid urate or are diagnosed as drug-related stones. Stones ultimately arise because of an unwanted phase change of these substances from liquid to solid state. Here we focus on the mechanisms of pathogenesis involved in CaOx, CaP, UA, and cystine stone formation, including recent developments in our understanding of related changes in human kidney tissue and of underlying genetic causes, in addition to current therapeutics.
Mutations within Sox2/SOX2 are associated with abnormalities in the hypothalamo-pituitary-gonadal axis in mice and humans
Authors: D. Kelberman
Journal: Journal of Clinical Investigation (2006)

The transcription factor SOX2 is expressed most notably in the developing CNS and placodes, where it plays critical roles in embryogenesis. Heterozygous de novo mutations in SOX2 have previously been associated with bilateral anophthalmia/microphthalmia, developmental delay, short stature, and male genital tract abnormalities. Here we investigated the role of Sox2 in murine pituitary development. Mice heterozygous for a targeted disruption of Sox2 did not manifest eye defects, but showed abnormal anterior pituitary development with reduced levels of growth hormone, luteinizing hormone, and thyroid-stimulating hormone. Consequently, we identified 8 individuals (from a cohort of 235 patients) with heterozygous sequence variations in SOX2. Six of these were de novo mutations, predicted to result in truncated protein products, that exhibited partial or complete loss of function (DNA binding, nuclear translocation, or transactivation). Clinical evaluation revealed that, in addition to bilateral eye defects, SOX2 mutations were associated with anterior pituitary hypoplasia and hypogonadotropic hypogonadism, variable defects affecting the corpus callosum and mesial temporal structures, hypothalamic hamartoma, sensorineural hearing loss, and esophageal atresia. Our data show that SOX2 is necessary for the normal development and function of the hypothalamo-pituitary and reproductive axes in both humans and mice.
Does the microbiota play a role in the pathogenesis of autoimmune diseases?
Authors: Mairi H McLean, Dario Dieguez, Lindsey M Miller, Howard A Young
Journal: Gut (2014)

The microbiota of the human metaorganism is not a mere bystander. These microbes have coevolved with us and are pivotal to normal development and homoeostasis. Dysbiosis of the GI microbiota is associated with many disease susceptibilities, including obesity, malignancy, liver disease and GI pathology such as IBD. It is clear that there is direct and indirect crosstalk between this microbial community and host immune response. However, the precise mechanism of this microbial influence in disease pathogenesis remains elusive and is now a major research focus. There is emerging literature on the role of the microbiota in the pathogenesis of autoimmune disease, with clear and increasing evidence that changes in the microbiota are associated with some of these diseases. Examples include type 1 diabetes, coeliac disease and rheumatoid arthritis, and these contribute significantly to global morbidity and mortality. Understanding the role of the microbiota in autoimmune diseases may offer novel insight into factors that initiate and drive disease progression, stratify patient risk for complications and ultimately deliver new therapeutic strategies. This review summarises the current status on the role of the microbiota in autoimmune diseases.
Efficacy and Tolerability of Olanzapine, Quetiapine, and Risperidone in the Treatment of Early Psychosis: A Randomized, Double-Blind 52-Week Comparison
Authors: Joseph P McEvoy, Jeffrey A Lieberman, Diana O Perkins, Robert M Hamer, Hongbin Gu, Arthur Lazarus, Dennis Sweitzer, Christina Olexy, Peter Weiden, Stephen D Strakowski
Journal: American Journal of Psychiatry (2007)

This 52-week randomized, double-blind, flexible-dose, multicenter study evaluated the overall effectiveness (as measured by treatment discontinuation rates) of olanzapine, quetiapine, and risperidone in patients early in the course of psychotic illness.Patients were randomly assigned to treatment with olanzapine (2.5-20 mg/day), quetiapine (100-800 mg/day), or risperidone (0.5-4 mg/day) administered in twice-daily doses. Statistical analyses tested for noninferiority in all-cause treatment discontinuation rates up to 52 weeks (primary outcome measure) based on a prespecified noninferiority margin of 20%.A total of 400 patients were randomly assigned to treatment with olanzapine (N=133), quetiapine (N=134), or risperidone (N=133). The mean modal prescribed daily doses were 11.7 mg for olanzapine, 506 mg for quetiapine, and 2.4 mg for risperidone. At week 52, all-cause treatment discontinuation rates were 68.4%, 70.9%, and 71.4% for olanzapine, quetiapine, and risperidone, respectively. Reductions in total score on the Positive and Negative Syndrome Scale (PANSS) were similar for the three treatment groups, but reductions in PANSS positive subscale scores were greater in the olanzapine group (at 12 weeks and at 52 weeks or withdrawal from study) and the risperidone group (at 12 weeks). The most common elicited adverse events for olanzapine were drowsiness (53%), weight gain (51%), and insomnia (38%); for quetiapine, drowsiness (58%), increased sleep hours (42%), and weight gain (40%); and for risperidone, drowsiness (50%), menstrual irregularities in women (47%), and weight gain (41%).Olanzapine, quetiapine, and risperidone demonstrated comparable effectiveness in early-psychosis patients, as indicated by similar rates of all-cause treatment discontinuation.
Prognostic relevance of acquired uniparental disomy in serous ovarian cancer
Authors: Musaffe Tuna, Zhenlin Ju, Marcel Smid, Christopher I Amos, Gordon B Mills
Journal: Molecular Cancer (2015)

Acquired uniparental disomy (aUPD) can lead to homozygosity for tumor suppressor genes or oncogenes. Our purpose is to determine the frequency and profile aUPD regions in serous ovarian cancer (SOC) and investigated the association of aUPD with clinical features and patient outcomes. We analyzed single nucleotide polymorphism (SNP) array-based genotyping data on 532 SOC specimens from The Cancer Genome Atlas database to identify aUPD regions. Cox univariate regression and Cox multivariate proportional hazards analyses were performed for survival analysis. We found that 94.7% of SOC samples harbored aUPD; the most common aUPD regions were in chromosomes 17q (76.7%), 17p (39.7%), and 13q (38.3%). In Cox univariate regression analysis, two independent regions of aUPD on chromosome 17q (A and C), and whole-chromosome aUPD were associated with shorter overall survival (OS), and five regions on chromosome 17q (A, D-G) and BRCA1 were associated with recurrence-free survival time. In Cox multivariable proportional hazards analysis, whole-chromosome aUPD was associated with shorter OS. One region of aUPD on chromosome 22q (B) was associated with unilateral disease. A statistically significant association was found between aUPD at TP53 loci and homozygous mutation of TP53 (p < 0.0001). aUPD is a common event and some recurrent loci are associated with a poor outcome for patients with serous ovarian cancer.
ORAL CONTRACEPTIVES AND CANCER
Authors: CliffordR. Kay, Pamela Pilkington, KeithJ. Randall, Mary Griffin, John Mcewan, D. Rivers, G.I.M. Swyer, Peter Diggory, M.P. Vessey, K. Mcpherson, J. Peto, M.C. Pike
Journal: The Lancet (1983)
Postmenopausal weight change and incidence of fracture: post hoc findings from Women's Health Initiative Observational Study and Clinical Trials
Authors: C. J. Crandall, V. O. Yildiz, J. Wactawski-Wende, K. C. Johnson, Z. Chen, S. B. Going, N. C. Wright, J. A. Cauley
Journal: BMJ (2015)

<b>Objectives</b> To determine associations between postmenopausal change in body weight and incidence of fracture and associations between voluntary and involuntary weight loss and risk of fracture. <b>Design</b> Post hoc analysis of data from the Women's Health Initiative Observational Study and Clinical Trials. <b>Setting</b> 40 clinical centers in the United States. <b>Participants</b> 120 566 postmenopausal women, aged 50-79 at baseline (1993-98), followed through 2013 (mean fracture follow-up duration 11 years from baseline). <b>Exposures</b> Annualized percentage change in measured body weight from baseline to year 3, classified as stable (&lt;5% change), weight loss (≥5%), or weight gain (≥5%). Self assessment of whether weight loss was intentional or unintentional. Cox proportional hazards regression models were adjusted for age, race/ethnicity, baseline body mass index (BMI), smoking, alcohol intake, level of physical activity, energy expenditure, calcium and vitamin D intake, physical function score, oophorectomy, hysterectomy, previous fracture, comorbidity score, and drug use. <b>Main outcomes</b> Incident self reported fractures of the upper limbs, lower limbs, and central body; hip fractures confirmed by medical records. <b>Results</b> Mean participant age was 63.3. Mean annualized percent weight change was 0.30% (95% confidence interval 0.28 to 0.32). Overall, 79 279 (65.6%) had stable weight; 18 266 (15.2%) lost weight; and 23 021 (19.0%) gained weight. Compared with stable weight, weight loss was associated with a 65% higher incidence rates of fracture in hip (adjusted hazard ratio 1.65, 95% confidence interval 1.49 to 1.82), upper limb (1.09, 1.03 to 1.16), and central body (1.30, 1.20 to 1.39); weight gain was associated with higher incidence rates of fracture in upper limb (1.10, 1.05 to 1.18) and lower limb (1.18, 1.12 to 1.25). Compared with stable weight, unintentional weight loss was associated with a 33% higher incidence rates of hip fracture (1.33, 1.19 to 1.47) and increased incidence rates of vertebral fracture (1.16, 1.06 to 1.26); intentional weight loss was associated with increased incidence rates of lower limb fracture (1.11, 1.05 to 1.17) and decreased incidence of hip fracture (0.85, 0.76 to 0.95). <b>Conclusions</b> Weight gain, weight loss, and intentional weight loss are associated with increased incidence of fracture, but associations differ by fracture location. Clinicians should be aware of fracture patterns after weight gain and weight loss.
Measuring cis-acting regulatory variants genome-wide: new insights into expression genetics and disease susceptibility
Authors: Wolfgang Sadee
Journal: Genome Medicine (2009)

Regulatory polymorphisms have emerged as a prevalent source of phenotypic variability, capable of driving rapid evolution. mRNA profiling combined with genome-wide genotyping of polymorphisms has revealed pervasive genetic influences on gene expression, acting both in cis and in trans. Measuring allelic ratios of RNA transcripts makes it possible to focus on cis-acting factors separately from trans-acting processes. Using large-scale allelic expression analysis, a recent study by Ge and colleagues demonstrates a high incidence of cis-acting regulatory variants, promising insights into the 'missing heritability' component of complex disorders. Here, I evaluate their results and discuss the limitations of the current approach and avenues for exploring disease risk, guiding successful therapy, early intervention, and prevention.
Access to invasive procedures can be audited by ethnic group
Authors: I. I Abubakar
Journal: BMJ (2002)

EDITOR—Feder et al reported findings from the appropriateness of coronary revascularisation (ACRE) study showing that among patients deemed clinically appropriate for coronary artery bypass grafting, south Asians are less likely than white patients to undergo procedures.1 They pointed out the lack of a mechanism to monitor ethnic differences in invasive management of coronary disease in the NHS. The quality of hospital …