tbuckley/cabot-search huggingface dataset:
FEV1 decline in occupational asthma
Authors: W Anees, V C Moore, P S Burge
Journal: Thorax (2006)

<b>Background:</b> In occupational asthma continued workplace exposure to the causative agent is associated with a poor prognosis. However, there is little information available on how rapidly lung function declines in those who continue to be exposed, nor how removal from exposure affects lung function. <b>Methods:</b> Forced expiratory volume in 1 second (FEV<sub>1</sub>) was studied in 156 consecutive subjects with occupational asthma (87% due to low molecular weight agents) using simple regression analyses to provide estimates of the decline in FEV<sub>1</sub> before and after removal from exposure. <b>Results:</b> In 90 subjects in whom FEV<sub>1</sub> measurements had been performed for at least 1 year before removal from exposure (median 2.9 years), the mean (SE) rate of decline in FEV<sub>1</sub> was 100.9 (17.7) ml/year. One year after removal from exposure FEV<sub>1</sub> had improved by a mean (SE) of 12.3 (31.6) ml. The mean (SE) decline in FEV<sub>1</sub> was 26.6 (18.0) ml/year in 86 subjects in whom measurements were made for at least 1 year (median 2.6 years) following removal from exposure. The decline in FEV<sub>1</sub> was not significantly worse in current smokers than in never smokers, nor was it affected by the use of inhaled corticosteroids. <b>Conclusion:</b> FEV<sub>1</sub> declines rapidly in exposed workers with occupational asthma. Following removal from exposure, FEV<sub>1</sub> continued to decline but at a slower rate, similar to the rate of decline in healthy adults.
Lower probability of patient survival with continuous peritoneal dialysis in the United States compared with Canada. Canada-USA (CANUSA) Peritoneal Dialysis Study Group.
Authors: D N Churchill, K E Thorpe, E F Vonesh, P R Keshaviah
Journal: Journal of the American Society of Nephrology (1997)

In a prospective cohort study of 680 incident continuous peritoneal dialysis (PD) patients in North America, dialysis in the United States compared with Canada was associated with a relative risk (RR) of death of 1.93 (95% confidence interval [CI], 1.14 to 3.28). The 2-yr survival probability was 79.7% in Canada and 63.2% in the United States. This difference was not explained by race, age, gender, functional status, insulin-dependent diabetes mellitus, history of cardiovascular disease (CVD), nutritional status, or adequacy of dialysis. Other potential explanatory variables were further evaluated. These included severity of CVD, residual renal function, race, differential transfer to hemodialysis or transplantation, patient compliance, modality selection bias, and incidence of endstage renal disease requiring dialysis. Cardiovascular morbidity and peritonitis probabilities were compared. The CVD severity index was not different between countries; the RR risk associated with dialysis in the United States remained high at 1.87 (95% CI, 1.09 to 3.19). Residual renal function at initiation of dialysis was not different between countries. The 2-yr survival for Caucasians was 77% in Canada and 55% in the United States. There was no difference in the probability of transfer to hemodialysis or transplantation. The RR of a nonfatal cardiovascular event in the United States compared with Canada was 1.80 (95% CI, 1.21 to 2.67). There was no difference in time to first peritonitis. The observed to predicted creatinine ratio, as an estimate of compliance, was 1.13 in Canada and 1.00 in the United States. The prevalence of PD in the study centers was 48% in Canada and 22% in the United States. The incidence of new dialysis patients in 1992 was 100/million population in Canada compared with 211/ million in the United States. The survival difference is not explained by age, gender, insulin-dependent diabetes mellitus, nutritional status, or adequacy of dialysis. Neither is it explained by race, severity of CVD, transfer to hemodialysis, transplantation, or an estimate of compliance. The lower proportion of patients receiving PD in the United States may represent a selection bias of uncertain direction. The higher acceptance rate for dialysis in the United States may explain, in part, the greater cardiovascular morbidity and the decreased survival observed.
Discovery and Prevalidation of Salivary Extracellular microRNA Biomarkers Panel for the Noninvasive Detection of Benign and Malignant Parotid Gland Tumors
Authors: Johannes H. Matse, Janice Yoshizawa, Xiaoyan Wang, David Elashoff, Jan G.M. Bolscher, Enno C.I. Veerman, Elisabeth Bloemena, David T.W. Wong
Journal: Clinical Cancer Research (2013)

This study was conducted to explore the differences in salivary microRNA (miRNA) profiles between patients with malignant or benign parotid gland tumors as a potential preoperative diagnostic tool of tumors in the salivary glands.Whole saliva samples from patients with malignant (n = 38) or benign (n = 29) parotid gland tumors were obtained from the Salivary Gland Tumor Biorepository (SGTB). After total RNA isolation, human miRNA cards were used for miRNA profiling. The differential miRNA expression was analyzed using two-sided Wilcoxon test. Quantitative real-time PCR (qRT-PCR) was used to validate selected miRNAs in an independent sample set. Receiver-operating characteristics curve and probability of malignancy was exploited to evaluate the diagnostic power of the validated miRNAs.With miRNA profiling, 57 of 750 investigated miRNAs were differently expressed, of which 54 showed higher miRNA expression in samples from patients with malignant tumors than those from patients with benign tumors. Validating the expression in an independent sample set of 9 miRNAs revealed indeed higher expression of miRNAs in malignant samples compared with benign samples. The expression of 6 validated miRNAs was statistically significantly different between the two groups (P < 0.05). A four miRNA combination was able to discriminate between saliva samples from patients with malignant tumors from those of patients with benign parotid gland tumors (sensitivity 69%, specificity 95%).Salivary miRNA profiles differ in saliva from patients with malignant from saliva from patients with a benign parotid gland tumor. These preliminary results are promising to develop a noninvasive diagnostic tool for diagnosing tumors in the salivary glands.
BRCA1 Ubiquitinates RPB8 in Response to DNA Damage
Authors: Wenwen Wu, Hiroyuki Nishikawa, Ryosuke Hayami, Ko Sato, Akeri Honda, Satoko Aratani, Toshihiro Nakajima, Mamoru Fukuda, Tomohiko Ohta
Journal: Cancer Research (2007)

Abstract The breast and ovarian tumor suppressor BRCA1 catalyzes untraditional polyubiquitin chains that could be a signal for processes other than proteolysis. However, despite intense investigations, the mechanisms regulated by the enzyme activity remain only partially understood. Here, we report that BRCA1-BARD1 mediates polyubiquitination of RPB8, a common subunit of RNA polymerases, in response to DNA damage. A proteomics screen identified RPB8 as a protein modified after epirubicin treatment in BRCA1-dependent manner. RPB8 interacted with BRCA1-BARD1 and was polyubiquitinated by BRCA1-BARD1 in vivo and in vitro. BRCA1-BARD1 did not destabilize RPB8 in vivo but rather caused an increase in the amount of soluble RPB8. Importantly, RPB8 was polyubiquitinated immediately after UV irradiation in a manner sensitive to BRCA1 knockdown by RNA interference. Substitution of five lysine residues of RPB8 with arginine residues abolished its ability to be ubiquitinated while preserving its polymerase activity. HeLa cell lines stably expressing this ubiquitin-resistant form of RPB8 exhibited UV hypersensitivity accompanied by up-regulated caspase activity. Our findings suggest that ubiquitination of a common subunit of RNA polymerases is a mechanism underlying BRCA1-dependent cell survival after DNA damage. [Cancer Res 2007;67(3):951–8]
Effect of <i>BRCA1/2</i> Mutations on Long-Term Survival of Patients With Invasive Ovarian Cancer: The National Israeli Study of Ovarian Cancer
Authors: Angela Chetrit, Galit Hirsh-Yechezkel, Yehuda Ben-David, Flora Lubin, Eitan Friedman, Siegal Sadetzki
Journal: Journal of Clinical Oncology (2007)

Purpose To evaluate the long-term survival of ovarian cancer (OvC) patients in total and by BRCA1/2 mutation status. Patients and Methods In a nationwide case-control study on OvC conducted in Israel between 1994 and 1999, 779 Jewish women with epithelial invasive OvC were tested for the three Ashkenazi Jewish founder mutations in BRCA1 (185delAG; 5382insC) and BRCA2 (6174delT) genes and followed for survival up to 2003. Of the 605 women of Ashkenazi origin, 213 (35.2%) carried a mutation in the BRCA1/2 genes. Clinical characteristics were abstracted from the patients' medical records. The Kaplan-Meier method, log-rank tests, and stepwise Cox regression model were used for survival analyses. Results The 5-year survival rate for the entire group was 39%. Median survival for carriers was significantly longer than for noncarriers (53.7 v 37.9 months, respectively; P = .002). This differential survival was pronounced among women diagnosed at stages III to IV (5-year survival rates of 38.1% and 24.5% for carriers and noncarriers, respectively; P &lt; .001) and for women with poor grade (45.4% v 31.5%, for carriers and noncarriers, respectively; P &lt; .001). These results remained significant after controlling for age at diagnosis, grade, and morphology. This benefit in prognosis was seen for both BRCA1 and BRCA2 carriers compared with noncarriers. During the study period (median follow-up, 6.2 years), being a BRCA1/2 mutation carrier decreased the mortality rate by 28%. Conclusion This study confirms that, among Ashkenazi OvC patients, BRCA1/2 mutations are associated with improved long-term survival. This may be due to distinct clinical behavior and/or to a better response to chemotherapy.
Selective ablation of Notch3 in HCC enhances doxorubicin’s death promoting effect by a p53 dependent mechanism
Authors: Catia Giovannini, Laura Gramantieri, Pasquale Chieco, Manuela Minguzzi, Federica Lago, Simona Pianetti, Eric Ramazzotti, Kenneth B. Marcu, Luigi Bolondi
Journal: Journal of Hepatology (2009)
Protective influenza-specific CD8 T cell responses require interactions with dendritic cells in the lungs
Authors: Jodi McGill, Nico Van Rooijen, Kevin L. Legge
Journal: The Journal of Experimental Medicine (2008)

Influenza infections induce a rapid, but transient, dendritic cell (DC) migration from the lungs to the lymph nodes (LNs) that is followed by substantial recruitment of DCs into the lungs without subsequent migration to the LNs. Given that peripheral DCs are primarily thought to be involved in the initiation of adaptive immunity after migration into lymphoid tissues, what role these newly lung-recruited DCs play in influenza virus immunity is unclear. In this study, we demonstrate that loss of non-LN migratory pulmonary DC subsets increases mortality, sustains higher viral titers, and impairs pulmonary CD8 T cell responses. Reconstitution of the lungs with pulmonary plasmacytoid DCs, CD8α+ DCs, or interstitial DCs restores CD8 T cell responses in a cell contact–, major histocompatability complex I–, and influenza peptide–dependent manner. Thus, after their initial activation in the LN, protective influenza-specific CD8 T cell responses require additional antigen-dependent interactions, specifically with DCs in the lungs.
Probable limited person-to-person transmission of highly pathogenic avian influenza A (H5N1) virus in China
Authors: Hua Wang, Zijian Feng, Yuelong Shu, Hongjie Yu, Lei Zhou, Rongqiang Zu, Yang Huai, Jie Dong, Changjun Bao, Leying Wen, Hong Wang, Peng Yang, Wei Zhao, Libo Dong, Minghao Zhou, Qiaohong Liao, Haitao Yang, Min Wang, Xiaojun Lu, Zhiyang Shi, Wei Wang, Ling Gu, Fengcai Zhu, Qun Li, Weidong Yin, Weizhong Yang, Dexin Li, Timothy M Uyeki, Yu Wang
Journal: The Lancet (2008)
Effect of capsaicin and chilli on ethanol induced gastric mucosal injury in the rat.
Authors: J Y Kang, C H Teng, A Wee, F C Chen
Journal: Gut (1995)

Capsaicin, the pungent ingredient of chilli, is gastroprotective against experimental gastric injury when given intragastrically. Epidemiological and clinical data suggest that chilli ingestion may have a beneficial effect on human peptic ulcer disease. This study showed a gastroprotective effect of intragastric capsaicin, in doses of 2 and 5 mg, on ethanol induced gastric mucosal injury using macroscopic, histological, scanning electron microscopic, and biochemical indices. Subcutaneous administration of 2 mg of capsaicin had the same gastroprotective effect as intragastric administration. Acute intragastric administration and chronic ingestion of chilli powder in doses comparable with that consumed in humans (up to 200 mg in single doses or 200 mg daily for four weeks) likewise protected the gastric mucosa. Both the mucosa and gastric juice had higher mucus contents when capsaicin or chilli rather than saline or solvent was used before ethanol challenge. In control animals capsaicin also increased gastric juice mucus content although the mucosal content was unaffected. Increased gastric mucus production may therefore be one mechanism by which capsaicin and chilli exert their gastroprotective effect although an alternative explanation is that the reduction in mucosal mucus depletion is secondary to the protective effect of capsaicin and chilli.
Circadian Clocks and Vascular Function
Authors: Georgios K. Paschos, Garret A. FitzGerald
Journal: Circulation Research (2010)

Abstract : The circadian clock regulates many aspects of physiology, including cardiovascular function. Internal oscillators exist in endothelial, smooth muscle cells, and fibroblasts of the vasculature. Vascular tone and thrombus formation, 2 key elements of vascular function with regard to adverse cardiovascular events, exhibit diurnal rhythmicity. In this review, we describe changes in vascular function that result from genetic disruption of discrete elements of the circadian clock.
Dexamethasone prevents visceral hyperalgesia but not colonic permeability increase induced by luminal protease-activated receptor-2 agonist in rats
Authors: R. Roka, A. Ait-Belgnaoui, C. Salvador-Cartier, R. Garcia-Villar, J. Fioramonti, H. Eutamene, L. Bueno
Journal: Gut (2007)

<b>Background:</b> Low-grade inflammation may play a role in the pathogenesis of irritable bowel syndrome (IBS). Although corticosteroids are potent inhibitors of inflammatory processes, only one study with corticosteroids in patients with postinfectious IBS exists, which suggests that prednisolone is not an effective treatment for IBS symptoms. <b>Aim:</b> To evaluate whether dexamethasone treatment prevents protease-activated receptor-2 (PAR-2) activation-induced visceral hyperalgesia and increased permeability in rats, and to determine whether the effects involve colonic mast cells. <b>Methods:</b> Abdominal contractions provoked by rectal distension were recorded in rats equipped with intramuscular electrodes. Changes in visceral hypersensitivity provoked by intracolonic administration of PAR-2-activating peptide (SLIGRL; H-serine-leucine-isoleucine-glycine-arginine-leucine-OH), changes in colonic mucosal rat mast cell protease-II (RMCP-II) content, mast cell count and PAR-2 expression were measured after a 4-day treatment with dexamethasone (1 mg/day/rat intraperitoneally) or its vehicle (water). The effect of mast cell stabiliser (doxantrazole, 1 mg/kg intraperitoneally, 2 h before and 6 h after intracolonic infusion of SLIGRL) on SLIGRL-induced visceral hyperalgesia was also assessed. The effects of SLIGRL and a mast cell degranulator (compound 48/80) on the permeability of colonic strips from vehicle- or dexamethasone-treated rats were investigated in Ussing chambers. <b>Results:</b> 4 days of dexamethasone as well as doxantrazole diminished the SLIGRL-induced hyperalgesia for all volumes of distension. This effect of dexamethasone was accompanied by a reduced responsiveness of colonic permeability to compound 48/80, and decreased RMCP-II content and mast cell number. Dexamethasone treatment did not influence colonic mucosal PAR-2 expression and permeability responsiveness to SLIGRL. <b>Conclusions:</b> Dexamethasone treatment improves PAR-2 agonist-induced visceral hypersensitivity but does not prevent PAR-2 agonist-induced increase in colonic permeability in rats. This effect is coupled with a reduction of colonic mast cell number and RMCP-II contents.
Loss of Fornix White Matter Volume as a Predictor of Cognitive Impairment in Cognitively Normal Elderly Individuals
Authors: Evan Fletcher, Mekala Raman, Philip Huebner, Amy Liu, Dan Mungas, Owen Carmichael, Charles DeCarli
Journal: JAMA Neurology (2013)

Magnetic resonance imaging markers of incipient cognitive decline among healthy elderly individuals have become important for both clarifying the biological underpinnings of dementia and clinically identifying healthy individuals at high risk of cognitive decline. Even though the role of hippocampal atrophy is well known in the later stages of decline, the ability of fornix-hippocampal markers to predict the earliest clinical deterioration is less clear.To examine the involvement of the hippocampus-fornix circuit in the very earliest stages of cognitive impairment and to determine whether the volumes of fornix white matter and hippocampal gray matter would be useful markers for understanding the onset of dementia and for clinical intervention.A longitudinal cohort of cognitively normal elderly participants received clinical evaluations with T1-weighted magnetic resonance imaging and diffusivity scans during repeated visits over an average of 4 years. Regression and Cox proportional hazards models were used to analyze the relationships between fornix and hippocampal measures and their predictive power for incidence and time of conversion from normal to impaired cognition.A cohort of community-recruited elderly individuals at the Alzheimer Disease Center of the University of California, Davis.A total of 102 cognitively normal elderly participants, with an average age of 73 years, recruited through community outreach using methods designed to enhance ethnic diversity.Our preliminary hypothesis was that fornix white matter volume should be a significant predictor of cognitive decline among normal elderly individuals and that fornix measures would be associated with gray matter changes in the hippocampus.Fornix body volume and axial diffusivity were highly significant predictors (P = .02 and .005, respectively) of cognitive decline from normal cognition. Hippocampal volume was not significant as a predictor of decline but was significantly associated with fornix volume and diffusivity (P = .004).This could be among the first studies establishing fornix degeneration as a predictor of incipient cognitive decline among healthy elderly individuals. Predictive fornix volume reductions might be explained at least in part by clinically silent hippocampus degeneration. The importance of this finding is that white matter tract measures may become promising candidate biomarkers for identifying incipient cognitive decline in a clinical setting, possibly more so than traditional gray matter measures.
Weil's Disease, with Tests for Liver Function
Authors: F. E. d. W. Cayley
Journal: BMJ (1949)

_~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~EIA JOURNAL_ picture of osteosclerosis with leucoerythroblastosis can occur in fluorosis.X rays have been known to produce fibrosis of the marrow and Joan Ross (1932) describes the effects of gamma radiation over a period of three years.The marrow showed hyperactivity of the myeloid and erythroid cells with a marked increase in megakaryocytes.The nutrient vessels showed endothelial thickening and intravascular thrombi.It is not beyond possibility that repeated doses of deep x rays over many years may produce the picture of myelofibrosis in polycythaemia rubra vera.
You Can’t Judge a Book by Its Cover
Authors: Philippe Menasché
Journal: Circulation (2006)

he current issue of Circulation reports 2 apparently conflicting studies 1,2 pertaining to the highly controversial issue of transdifferentiation of bone marrowderived cells into cardiomyocytes.The study by Iwasaki et al 1 entailed intramyocardial injections of human CD34 ϩ progenitors 20 minutes after the creation of a myocardial infarction in sex-mismatched, immunodeficient athymic mice.The results, assessed 28 days after transplantation, demonstrate a dose-dependent improvement in regional and global left ventricular function, a limitation of remodeling, and an increase in capillary density.These functional benefits are associated with a cardiac differentiation of the engrafted CD34 ϩ cells demonstrated by a double immunofluorescent staining for human-and cardiac-specific markers.Expression of cardiac genes unraveled by real-time polymerase chain reaction is also taken as additional evidence for the cardiomyocytic conversion of the CD34 ϩ progenitor cells, although this conclusion is compounded by the concomitant observation of fusion events between human and mouse cells demonstrated by fluorescent hybridization in situ, using probes specific for these 2 species.Differentiation of the CD34 ϩ progenitors into smooth muscle and endothelial cells is also reported on the basis of similar double-staining immunofluorescent patterns.In contrast, the second article, by Gruh et al, 2 does not demonstrate any conversion of human endothelial progenitor cells cocultured with neonatal rat cardiomyocytes.This study has carefully deciphered the potential causes of artifacts that may arise from the use of flow cytometry and conventional 2-dimensional immunofluorescence microscopy and lead to misinterpretations of phenotypic changes incurred by transplanted cells.Indeed, even 3-dimensional confocal microscopy failed to provide a conclusive interpretation for approximately 12% of the doublestained cells (ie, those expressing markers of both endothelial and cardiac lineages), thereby highlighting the caution with which these putative transdifferentiation events should be analyzed.Failure of additional real-time polymerase chain reaction to detect cardiac transcription factors further supports the authors' skepticism about the ability of CD34 ϩ progenitor cells to cross their lineage boundaries, at least in this setting of coculture experiments.