tbuckley/cabot-search huggingface dataset:
Neurofibromatosis-associated lung disease: a case series and literature review
Authors: A. C. Zamora, H. R. Collard, P. J. Wolters, W. R. Webb, T. E. King
Journal: European Respiratory Journal (2006)

An association of neurofibromatosis with diffuse lung disease (NF-DLD) has been described, but its true prevalence and characteristics remain unclear. The objective of the present study was to define diffuse lung disease in patients with neurofibromatosis. A retrospective case series and literature review in a tertiary care academic medical centre is reported in which medical records, chest radiographs and high-resolution computed tomography (HRCT) scans were reviewed. A total of 55 adult patients with neurofibromatosis were identified, three of whom had NF-DLD. A literature review revealed 16 articles reporting 61 additional cases, yielding a total of 64 NF-DLD cases. The mean age of patients was 50 yrs. Males outnumbered females; most reported dyspnoea. Of the 16 subjects with documented smoking histories, 12 were ever-smokers. Eight patients had HRCT scan results demonstrating ground-glass opacities (37%), bibasilar reticular opacities (50%), bullae (50%), cysts (25%) and emphysema (25%); none had honeycombing. A group of 14 patients had surgical biopsy results that showed findings of interstitial fibrosis (100%) and interstitial inflammation (93%). In conclusion, neurofibromatosis with diffuse lung disease is a definable clinical entity, characterised by upper lobe cystic and bullous disease and lower lobe fibrosis. Its relationship to smoking remains unclear.
A Single Factor Underlies the Metabolic Syndrome: A Confirmatory Factor Analysis
Authors: Jeanne M. McCaffery, Biing-Jiun Shen, John F. Todaro, Raymond S. Niaura
Journal: Diabetes Care (2006)

included in the original validation study.Therefore, the validity of the calculated glycemic index values is essentially unknown.However, given the relatively low correlation coefficients for quantity of total carbohydrate, starches, and sucrose, it would seem unlikely that subtle differences in the quality (i.e., glycemic index) of that carbohydrate can be accurately assessed.The authors note that correlations for carbohydrate were higher in urban non-Hispanic white subjects (Ͻ20% of the sample) and that stratification for ethnicity did not alter their conclusions.However, due to the relatively small sample size, subanalysis may not have had sufficient statistical power to detect associations.Interestingly, observational studies that found no association between glycemic index, glycemic load, and incidence of type 2 diabetes (8,9) also had validation correlation coefficients for total carbohydrate that were Ͻ0.5.In contrast, those studies finding glycemic index, glycemic load, or both to be predictive of diabetes (5,6,10) had r values Ͼ0.6.Given the limitations of the IRAS study in relation to its ability to accurately assess total carbohydrate intake, starches, and sucrose, we believe that the conclusions drawn from the study of Liese et al., i.e., that glycemic index and glycemic load are not related to measures of insulin sensitivity, insulin secretion, and adiposity, should be interpreted with caution.
The high incidence of intestinal volvulus in Iran
Authors: F. Saidi
Journal: Gut (1969)

The incidence of intestinal volvulus gleaned from the world9s medical literature spread over the past seven decades supports the contention that this bowel disorder has distinct geographical predilections. Sigmoid volvulus, invariably superimposed upon a redundancy of this part of the bowel, probably results from a functional disturbance of the colon mediated perhaps by a high-residue vegetable diet. The same factors appear to hold for small bowel volvulus, though caecal volvulus occurs strictly on the basis of preexisting anatomical abnormalities.
Anatomy of health effects of Mediterranean diet: Greek EPIC prospective cohort study
Authors: A. Trichopoulou, C. Bamia, D. Trichopoulos
Journal: BMJ (2009)

To investigate the relative importance of the individual components of the Mediterranean diet in generating the inverse association of increased adherence to this diet and overall mortality.Prospective cohort study.Greek segment of the European Prospective Investigation into Cancer and nutrition (EPIC).23 349 men and women, not previously diagnosed with cancer, coronary heart disease, or diabetes, with documented survival status until June 2008 and complete information on nutritional variables and important covariates at enrolment.All cause mortality.After a mean follow-up of 8.5 years, 652 deaths from any cause had occurred among 12 694 participants with Mediterranean diet scores 0-4 and 423 among 10 655 participants with scores of 5 or more. Controlling for potential confounders, higher adherence to a Mediterranean diet was associated with a statistically significant reduction in total mortality (adjusted mortality ratio per two unit increase in score 0.864, 95% confidence interval 0.802 to 0.932). The contributions of the individual components of the Mediterranean diet to this association were moderate ethanol consumption 23.5%, low consumption of meat and meat products 16.6%, high vegetable consumption 16.2%, high fruit and nut consumption 11.2%, high monounsaturated to saturated lipid ratio 10.6%, and high legume consumption 9.7%. The contributions of high cereal consumption and low dairy consumption were minimal, whereas high fish and seafood consumption was associated with a non-significant increase in mortality ratio.The dominant components of the Mediterranean diet score as a predictor of lower mortality are moderate consumption of ethanol, low consumption of meat and meat products, and high consumption of vegetables, fruits and nuts, olive oil, and legumes. Minimal contributions were found for cereals and dairy products, possibly because they are heterogeneous categories of foods with differential health effects, and for fish and seafood, the intake of which is low in this population.
CD22 associates with protein tyrosine phosphatase 1C, Syk, and phospholipase C-gamma(1) upon B cell activation.
Authors: C L Law, S P Sidorenko, K A Chandran, Z Zhao, S H Shen, E H Fischer, E A Clark
Journal: The Journal of Experimental Medicine (1996)

Cross-linking B cell antigen receptor (BCR) elicits early signal transduction events, including activation of protein tyrosine kinases, phosphorylation of receptor components, activation of phospholipase C-gamma (PLC-gamma), and increases in intracellular free Ca2+. In this article, we report that cross-linking the BCR led to a rapid translocation of cytosolic protein tyrosine phosphatase (PTP) 1C to the particulate fraction, where it became associated with a 140-150-kD tyrosyl-phosphorylated protein. Western blotting analysis identified this 140-150-kD protein to be CD22. The association of PTP-1C with CD22 was mediated by the NH2-terminal Src homology 2 (SH2) domain of PTP-1C. Complexes of either CD22/PTP-1C/Syk/PLC-gamma(1) could be isolated from B cells stimulated by BCR engagement or a mixture of hydrogen peroxidase and sodium orthovanadate, respectively. The binding of PLC-gamma(1) and Syk to tyrosyl-phosphorylated CD22 was mediated by the NH2-terminal SH2 domain of PLC-gamma(1) and the COOH-terminal SH2 domain of Syk, respectively. These observations suggest that tyrosyl-phosphorylated CD22 may downmodulate the activity of this complex by dephosphorylation of CD22, Syk, and/or PLC-gamma(1). Transient expression of CD22 and a null mutant of PTP-1C (PTP-1CM) in COS cells resulted in an increase in tyrosyl phosphorylation of CD22 and its interaction with PTP-1CM. By contrast, CD22 was not tyrosyl phosphorylated or associated with PTP-1CM in the presence of wild-type PTP-1C. These results suggest that tyrosyl-phosphorylated CD22 may be a substrate for PTP-1C regulates tyrosyl phosphorylation of CD22.
Endometriosis: cost estimates and methodological perspective
Authors: S. Simoens, L. Hummelshoj, T. D'Hooghe
Journal: Human Reproduction Update (2007)

This article aims to provide a systematic review of estimates and methodology of studies quantifying the costs of endometriosis. Included studies were cost-of-illness analyses quantifying the economic impact of endometriosis and cost analyses calculating diagnostic and treatment costs of endometriosis. Annual healthcare costs and costs of productivity loss associated with endometriosis have been estimated at $2801 and $1023 per patient, respectively. Extrapolating these findings to the US population, this study calculated that annual costs of endometriosis attained $22 billion in 2002 assuming a 10% prevalence rate among women of reproductive age. These costs are considerably higher than those related to Crohn's disease or to migraine. To date, it is not possible to determine whether a medical approach is less expensive than a surgical approach to treating endometriosis in patients presenting with chronic pelvic pain. Evidence of endometriosis costs in infertile patients is largely lacking. Cost estimates were biased due to the absence of a control group of patients without endometriosis, inadequate consideration of endometriosis recurrence and restricted scope of costs. There is a need for more and better-designed studies that carry out longitudinal analyses of patients until the cessation of their symptoms or that model the chronic nature of endometriosis.
Evolutionary Origin and Human-Specific Expansion of a Cancer/Testis Antigen Gene Family
Authors: Qu Zhang, Bing Su
Journal: Molecular Biology and Evolution (2014)

Cancer/testis (CT) antigens are encoded by germline genes and are aberrantly expressed in a number of human cancers. Interestingly, CT antigens are frequently involved in gene families that are highly expressed in germ cells. Here, we presented an evolutionary analysis of the CTAGE (cutaneous T-cell-lymphoma-associated antigen) gene family to delineate its molecular history and functional significance during primate evolution. Comparisons among human, chimpanzee, gorilla, orangutan, macaque, marmoset, and other mammals show a rapid and primate specific expansion of CTAGE family, which starts with an ancestral retroposition in the haplorhini ancestor. Subsequent DNA-based duplications lead to the prosperity of single-exon CTAGE copies in catarrhines, especially in humans. Positive selection was identified on the single-exon copies in comparison with functional constraint on the multiexon copies. Further sequence analysis suggests that the newly derived CTAGE genes may obtain regulatory elements from long terminal repeats. Our result indicates the dynamic evolution of primate genomes, and the recent expansion of this CT antigen family in humans may confer advantageous phenotypic traits during early human evolution.
Randomized, Placebo-Controlled, Double-Blind Clinical Trial of Sertraline in the Treatment of Depression Complicating Alzheimer’s Disease: Initial Results From the Depression in Alzheimer’s Disease Study
Authors: Constantine G. Lyketsos, Jeannie-Marie E. Sheppard, Cynthia D. Steele, Susan Kopunek, Martin Steinberg, Alva S. Baker, Jason Brandt, Peter V. Rabins
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: This study evaluated the efficacy and safety of sertraline in the treatment of major depression in 22 outpatients with Alzheimer's disease. METHOD: Twelve of the 22 patients were given sertraline and 10 were given placebo by random group assignment for 12 weeks. Response to treatment was measured by using the Cornell Scale for Depression in Dementia. The patients were also assessed with the Hamilton Depression Rating Scale, the activities of daily living subscale of the Psychogeriatric Dependency Rating Scales, and the Mini-Mental State. RESULTS: After 12 weeks of double-blind, placebo-controlled treatment, nine of the patients given sertraline and two of those given placebo were at least partial responders. Patients given sertraline had significantly greater mean declines from baseline in Cornell Scale for Depression in Dementia scores; the bulk of antidepressant response occurred by the third week of treatment. CONCLUSIONS: Sertraline is superior to placebo in reducing depression in patients with Alzheimer's disease who also suffer from major depression.
Selective glucocorticoid receptor modulation: New directions with non-steroidal scaffolds
Authors: Nora Sundahl, Jolien Bridelance, Claude Libert, Karolien De Bosscher, Ilse M. Beck
Journal: Pharmacology & Therapeutics (2015)

Glucocorticoids remain the frontline treatment for inflammatory disorders, yet represent a double-edged sword with beneficial therapeutic actions alongside adverse effects, mainly in metabolic regulation. Considerable efforts were made to improve this balance by attempting to amplify therapeutic beneficial anti-inflammatory actions and to minimize adverse metabolic actions. Most attention has focused on the development of novel compounds favoring the transrepressing actions of the glucocorticoid receptor, assumed to be important for anti-inflammatory actions, over the transactivating actions, assumed to underpin the undesirable actions. These compounds are classified as selective glucocorticoid receptor agonists (SEGRAs) or selective glucocorticoid receptor modulators (SEGRMs). The latter class is able to modulate the activity of a GR agonist and/or may not classically bind the glucocorticoid receptor ligand-binding pocket. SEGRAs and SEGRMs are collectively denominated SEGRAMs (selective glucocorticoid receptor agonists and modulators). Although this transrepression vs transactivation concept proved to be too simplistic, the developed SEGRAMs were helpful in elucidating various molecular actions of the glucocorticoid receptor, but have also raised many novel questions. We discuss lessons learned from recent mechanistic studies of selective glucocorticoid receptor modulators. This is approached by analyzing recent experimental insights in comparison with knowledge obtained using mutant GR research, thus clarifying the current view on the SEGRAM field. These insights also contribute to our understanding of the processes controlling glucocorticoid-mediated side effects as well as glucocorticoid resistance. Our perspective on non-steroidal SEGRAs and SEGRMs considers remaining opportunities to address research gaps in order to harness the potential for more safe and effective glucocorticoid receptor therapies.
Functional GI disorders: from animal models to drug development
Authors: E A Mayer, S Bradesi, L Chang, B M R Spiegel, J A Bueller, B D Naliboff
Journal: Gut (2007)

Despite considerable efforts by academic researchers and by the pharmaceutical industry, the development of novel pharmacological treatments for irritable bowel syndrome (IBS) and other functional gastrointestinal (GI) disorders has been slow and disappointing. The traditional approach to identifying and evaluating novel drugs for these symptom-based syndromes has relied on a fairly standard algorithm using animal models, experimental medicine models and clinical trials. In the current article, the empirical basis for this process is reviewed, focusing on the utility of the assessment of visceral hypersensitivity and GI transit, in both animals and humans, as well as the predictive validity of preclinical and clinical models of IBS for identifying successful treatments for IBS symptoms and IBS-related quality of life impairment. A review of published evidence suggests that abdominal pain, defecation-related symptoms (urgency, straining) and psychological factors all contribute to overall symptom severity and to health-related quality of life. Correlations between readouts obtained in preclinical and clinical models and respective symptoms are small, and the ability to predict drug effectiveness for specific as well as for global IBS symptoms is limited. One possible drug development algorithm is proposed which focuses on pharmacological imaging approaches in both preclinical and clinical models, with decreased emphasis on evaluating compounds in symptom-related animal models, and more rapid screening of promising candidate compounds in man.
Origins and Prevalence of the American Founder Mutation of <i>MSH2</i>
Authors: Mark Clendenning, Mark E. Baze, Shuying Sun, Kyle Walsh, Sandya Liyanarachchi, Dan Fix, Victoria Schunemann, Ilene Comeras, Molly Deacon, Jane F. Lynch, Gordon Gong, Brittany C. Thomas, Stephen N. Thibodeau, Henry T. Lynch, Heather Hampel, Albert de la Chapelle
Journal: Cancer Research (2008)

Abstract Large germline deletions within the mismatch repair gene MSH2 account for a significant proportion (up to 20%) of all deleterious mutations of this gene which are associated with Lynch syndrome. An exons 1 to 6 deletion of MSH2, originally reported in nine families, has been associated with a founding event within the United States, which genealogic studies had previously dated to 1727, and the number of present day carriers was estimated to be 18,981. Here, we report the development of a robust multiplex PCR which has assisted in the detection of 32 new families who carry the MSH2 American Founder Mutation (AFM). By offering testing to family members, 126 carriers of the AFM have been identified. Extensive genealogic studies have connected 27 of the 41 AFM families into seven extended pedigrees. These extended families have been traced back to around the 18th century without any evidence of further convergence between them. Characterization of the genomic sequence flanking the deletion and the identification of a common disease haplotype of between 0.6 and 2.3 Mb in all probands provides evidence for a common ancestor between these extended families. The DMLE+2.2 software predicts an age of ∼500 years (95% confidence interval, 425–625) for this mutation. Taken together, these data are suggestive of an earlier founding event than was first thought, which likely occurred in a European or a Native American population. The consequences of this finding would be that the AFM is significantly more frequent in the United States than was previously predicted. [Cancer Res 2008;68(7):2145–53]
Thrombomodulin Gene Variants Are Associated With Increased Mortality After Coronary Artery Bypass Surgery in Replicated Analyses
Authors: Robert L. Lobato, William D. White, Joseph P. Mathew, Mark F. Newman, Peter K. Smith, Charles B. McCants, John H. Alexander, Mihai V. Podgoreanu
Journal: Circulation (2011)

We tested the hypothesis that genetic variation in thrombotic and inflammatory pathways is independently associated with long-term mortality after coronary artery bypass graft (CABG) surgery.Two separate cohorts of patients undergoing CABG surgery at a single institution were examined, and all-cause mortality between 30 days and 5 years after the index CABG was ascertained from the National Death Index. In a discovery cohort of 1018 patients, a panel of 90 single-nucleotide polymorphisms (SNPs) in 49 candidate genes was tested with Cox proportional hazard models to identify clinical and genomic multivariate predictors of incident death. After adjustment for multiple comparisons and clinical predictors of mortality, the homozygote minor allele of a common variant in the thrombomodulin (THBD) gene (rs1042579) was independently associated with significantly increased risk of all-cause mortality (hazard ratio, 2.26; 95% CI, 1.31 to 3.92; P=0.003). Six tag SNPs in the THBD gene, 1 of which (rs3176123) in complete linkage disequilibrium with rs1042579, were then assessed in an independent validation cohort of 930 patients. After multivariate adjustment for the clinical predictors identified in the discovery cohort and multiple testing, the homozygote minor allele of rs3176123 independently predicted all-cause mortality (hazard ratio, 3.6; 95% CI, 1.67 to 7.78; P=0.001).In 2 independent cardiac surgery cohorts, linked common allelic variants in the THBD gene are independently associated with increased long-term mortality risk after CABG and significantly improve the classification ability of traditional postoperative mortality prediction models.
154 Immunogenicity and safety of a novel adjuvanted hepatitis B candidate vaccine in liver transplant patients
Authors: F. Nevens, J.N. Zuckerman, A. Burroughs, M.C. Jung, J.M. Bayas, B. Kallinowski, M. de la Mata, C. Duvoux, P. Neuhaus, F. Saliba, M. Buti, J.P. Zarski, F. Pons, C. Vanlemmens, V. Hamtiaux, M. Stoffel
Journal: Journal of Hepatology (2004)
Survival after Treatment with Phenylacetate and Benzoate for Urea-Cycle Disorders
Authors: Gregory M. Enns, Susan A. Berry, Gerard T. Berry, William J. Rhead, Saul W. Brusilow, Ada Hamosh
Journal: New England Journal of Medicine (2007)

The combination of intravenous sodium phenylacetate and sodium benzoate has been shown to lower plasma ammonium levels and improve survival in small cohorts of patients with historically lethal urea-cycle enzyme defects.
Functional analysis of the human vascular cell adhesion molecule 1 promoter.
Authors: A S Neish, A J Williams, H J Palmer, M Z Whitley, T Collins
Journal: The Journal of Experimental Medicine (1992)

The vascular cell adhesion molecule 1 (VCAM-1) is a 110-kD member of the immunoglobulin gene superfamily expressed on the surface of interleukin 1 beta- or tumor necrosis factor alpha (TNF)-stimulated endothelial cells. The cell surface protein functions as an inducible adhesion receptor for circulating mononuclear leukocytes and some tumor cells. We have previously characterized the genomic organization of the VCAM1 gene and described its chromosomal localization. In this report, the promoter of the VCAM1 gene is characterized. New transcription of the VCAM1 gene occurred when endothelial cells were treated with TNF. Fusion plasmids containing the 5' flanking sequence of the VCAM1 gene and the chloramphenicol acetyltransferase reporter gene were used to identify cis-acting sequences that direct the cytokine-induced transcription. When transfected into bovine aortic endothelial cells, constructs containing 755 bp of the 5' flanking sequence were induced by TNF. Within the cytokine-responsive region of the core promoter were functional NF-kappa B and GATA elements. Upstream of the core promoter, the VCAM1 5' flanking sequence contained a negative regulatory activity. NF-kappa B-mediated activation of VCAM1 gene expression may lead to endothelial expression of a mononuclear leukocyte adhesion molecule associated with initial events in the development of an atherosclerotic lesion.
PPM1H Is a p27 Phosphatase Implicated in Trastuzumab Resistance
Authors: Si Tuen Lee-Hoeflich, Thinh Q. Pham, Don Dowbenko, Xander Munroe, James Lee, Li Li, Wei Zhou, Peter M. Haverty, Kanan Pujara, Jeremy Stinson, Sara M. Chan, Jeffrey Eastham-Anderson, Ajay Pandita, Somasekar Seshagiri, Klaus P. Hoeflich, Gulisa Turashvili, Karen A. Gelmon, Samuel A. Aparicio, David P. Davis, Mark X. Sliwkowski, Howard M. Stern
Journal: Cancer Discovery (2011)

The HER2 oncogene is overexpressed or amplified in 20% of breast cancers. HER2-positive cancer historically portends a poor prognosis, but the HER2-targeted therapy trastuzumab mitigates this otherwise ominous distinction. Nevertheless, some patients suffer disease recurrence despite trastuzumab, and metastatic disease remains largely incurable due to innate and acquired resistance. Thus, understanding trastuzumab resistance remains an unmet medical need. Through RNA interference screening, we discovered that knockdown of the serine/threonine phosphatase PPM1H confers trastuzumab resistance via reduction in protein levels of the tumor suppressor p27. PPM1H dephosphorylates p27 at threonine 187, thus removing a signal for proteasomal degradation. We further determined that patients whose tumors express low levels of PPM1H trend towards worse clinical outcome on trastuzumab. Identifying PPM1H as a novel p27 phosphatase reveals new insight into how cancer cells destabilize a well-recognized tumor suppressor. Furthermore, low PPM1H expression may identify a subset of HER2-positive tumors that are harder to treat.