tbuckley/cabot-search huggingface dataset:
Adjunctive resectional lung surgery for extensively drug-resistant tuberculosis
Authors: G. Dravniece, K. P. Cain, T. H. Holtz, V. Riekstina, V. Leimane, R. Zaleskis
Journal: European Respiratory Journal (2009)

Extensively drug-resistant (XDR) tuberculosis (TB) poses significant management challenges as there are limited pharmacological treatment options for cure. Adjunctive resectional lung surgery decreases case-fatality rates for some patients with multidrug-resistant tuberculosis (MDR-TB), but its use has not been well documented for patients with XDR-TB. We describe 17 XDR-TB patients treated with surgery as part of their case management in Latvia during 1999–2005. One patient had no previous TB treatment history, 10 were previously treated for drug-susceptible TB and six were previously treated for MDR-TB. Mycobacterium tuberculosis isolates from the 17 patients were resistant to a mean of 9.2 drugs. Due to failure of pharmacological therapy, one due to a large cavity and one due to pulmonary haemorrhage, 15 patients were treated with surgery. Despite failure of pharmacological treatment in 15 out of 17 patients, eight (47%) were cured with adjunctive surgical treatment. Surgery should be explored as a possible treatment option for patients with XDR-TB.
Alterations in adhesion junction precede gap junction remodelling during the development of heart failure in cardiomyopathic hamsters
Authors: Masaaki Yoshida, Tomoko Ohkusa, Tadamitsu Nakashima, Hiroki Takanari, Masafumi Yano, Genzou Takemura, Haruo Honjo, Itsuo Kodama, Yoichi Mizukami, Masunori Matsuzaki
Journal: Cardiovascular Research (2011)

The intercalated disc (ID) contains two complexes, the adhesion junction (AJ) and the gap junction (GJ). We studied ID remodelling and its potential role in arrhythmogenesis and investigated the effects of olmesartan on ID remodelling during development of heart failure (HF) in UM-X7.1 cardiomyopathic hamsters. The UM-X7.1 hamsters showed left ventricular (LV) hypertrophy by the age of 10–15 weeks and a moderate impairment in LV contractility at 20 weeks. At age 10–15 weeks, 10–20% of the hamsters died suddenly without HF, and ventricular tachycardia (VT)/ventricular fibrillation (VF) was induced in ∼30% of hamsters. Electron microscopy showed that density linking cell-to-cell adhesion was irregular and unclearly defined, and filamentous structures attached to electron-dense components were arranged in disorder. Western blotting showed that the total cellular expression level of β-catenin was decreased, and expression of nuclear β-catenin, which functions as a T-cell factor/lymphocyte enhancer binding factor transcriptional activator, was also remarkably decreased. At age 20 weeks, LV connexin43 expression showed a remarkable decrease, and the VT/VF induction rate was ∼90%. In UM-X7.1 hamsters, olmesartan improved abnormal ID ultrastructural changes, attenuated the decrease of total cellular and nuclear β-catenin expression, decreased VT/VF induction, and improved survival rate. These results suggest that changes in AJ protein precede connexin43 GJ alterations, and ID remodelling might contribute to arrhythmogenesis during the development of HF. Angiotensin receptor blockade might be a new therapy for lethal ventricular arrhythmia by modulating both AJ and GJ remodelling.
FFP:RBC Resuscitation Ratio and Post-Shock Fluid Uptake
Authors: Charles E. Lucas, Anna M. Ledgerwood
Journal: JAMA Surgery (2012)

To assess the effects of the fresh frozen plasma (FFP) to red blood cell (RBC) ratio and balanced electrolyte solution (BES) to RBC ratio during resuscitation of severely injured patients on the duration of the postoperative fluid uptake period (phase 2) as well as the fluid (BES) needs, weight gain, and hypoproteinemia in phase 2.The 316 patients were hypotensive (systolic blood pressure=81 mm Hg) and tachycardic (117/min), with an average shock time (systolic blood pressure 80 mm Hg) of 31 minutes in the operating room (OR); they received 14.2 RBC units, 854 mL of FFP, and 11.5 L of BES while in the OR. Phase 2 averaged 29.2 hours, where the patients gained 8.4 kg, had a serum albumin level of 2.6 g per day, and received 8.6 L of BES. The phase 2 time, BES needs, weight gain, and hypoproteinemia were correlated with systolic blood pressure, admission pulse rate, arterial pH, shock time, RBC, FFP, and BES; the FFP:RBC, BES:RBC, and BES: FFP ratios were given in the OR.Shock time had the best correlation with RBC, FFP, and BES administration in the OR as well as with phase 2 duration, BES needs, weight gain, and hypoproteinemia. There was no significant correlation with OR FFP: RBC, BES:RBC, or BES:FFP ratios and phase 2 hypoproteinemia or weight gain. The FFP:RBC ratio in the OR correlated directly with phase 2 duration and BES needs (P=.001); in contrast, the BES:RBC ratio in the OR correlated (P.001) inversely with phase 2 duration and BES needs.The severity of shock is best predicted by shock time and the RBC, FFP, and BES infusions in the OR. Contrary to recent reports, the FFP:RBC ratio in the OR correlates directly with duration and BES needs of phase 2, whereas the BES:RBC ratio correlates inversely with phase 2 duration and BES needs.
Microbial translocation is a cause of systemic immune activation in chronic HIV infection
Authors: Jason M Brenchley, David A Price, Timothy W Schacker, Tedi E Asher, Guido Silvestri, Srinivas Rao, Zachary Kazzaz, Ethan Bornstein, Olivier Lambotte, Daniel Altmann, Bruce R Blazar, Benigno Rodriguez, Leia Teixeira-Johnson, Alan Landay, Jeffrey N Martin, Frederick M Hecht, Louis J Picker, Michael M Lederman, Steven G Deeks, Daniel C Douek
Journal: Nature Medicine (2006)
Keratin K6irs is specific to the inner root sheath of hair follicles in mice and humans
Authors: R.M. Porter, L.D. Corden, D.P. Lunny, F.J.D. Smith, E.B. Lane, W.H.I. Mclean
Journal: British Journal of Dermatology (2001)

Background Keratins are a multigene family of intermediate filament proteins that are differentially expressed in specific epithelial tissues. To date, no type II keratins specific for the inner root sheath of the human hair follicle have been identified. Objectives To characterize a novel type II keratin in mice and humans. Methods Gene sequences were aligned and compared by BLAST analysis. Genomic DNA and mRNA sequences were amplified by polymerase chain reaction (PCR) and confirmed by direct sequencing. Gene expression was analysed by reverse transcription (RT)–PCR in mouse and human tissues. A rabbit polyclonal antiserum was raised against a C-terminal peptide derived from the mouse K6irs protein. Protein expression in murine tissues was examined by immunoblotting and immunofluorescence. Results Analysis of human expressed sequence tag (EST) data generated by the Human Genome Project revealed a fragment of a novel cytokeratin mRNA with characteristic amino acid substitutions in the 2B domain. No further human ESTs were found in the database; however, the complete human gene was identified in the draft genome sequence and several mouse ESTs were identified, allowing assembly of the murine mRNA. Both species' mRNA sequences and the human gene were confirmed experimentally by PCR and direct sequencing. The human gene spans more than 16 kb of genomic DNA and is located in the type II keratin cluster on chromosome 12q. A comprehensive immunohistochemical survey of expression in the adult mouse by immunofluorescence revealed that this novel keratin is expressed only in the inner root sheath of the hair follicle. Immunoblotting of murine epidermal keratin extracts revealed that this protein is specific to the anagen phase of the hair cycle, as one would expect of an inner root sheath marker. In humans, expression of this keratin was confirmed by RT–PCR using mRNA derived from plucked anagen hairs and epidermal biopsy material. By this means, strong expression was detected in human hair follicles from scalp and eyebrow. Expression was also readily detected in human palmoplantar epidermis; however, no expression was detected in face skin despite the presence of fine hairs histologically. Conclusions This new keratin, designated K6irs, is a valuable histological marker for the inner root sheath of hair follicles in mice and humans. In addition, this keratin represents a new candidate gene for inherited structural hair defects such as loose anagen syndrome.
Strategies and Resources to Address Colorectal Cancer Screening Rates and Disparities in the United States and Globally
Authors: Michael B. Potter
Journal: Annual Review of Public Health (2013)

Colorectal cancer is a significant cause of mortality in the United States and globally. In the United States, increased access to screening and effective treatment has contributed to a reduction in colorectal cancer incidence and mortality for the general population, though significant disparities persist. Worldwide, the disparities are even more pronounced, with vastly different colorectal cancer mortality rates and trends among nations. Newly organized colorectal cancer screening programs in economically developed countries with a high burden of colorectal cancer may provide pathways to reduce these disparities over time. This article provides an overview of colorectal cancer incidence, mortality, screening, and disparities in the United States and other world populations. Promising strategies and resources are identified to address colorectal cancer screening rates and disparities in the United States and worldwide.
A virus-encoded telomerase RNA promotes malignant T cell lymphomagenesis
Authors: Sascha Trapp, Mark S. Parcells, Jeremy P. Kamil, Daniel Schumacher, B. Karsten Tischer, Pankaj M. Kumar, Venugopal K. Nair, Nikolaus Osterrieder
Journal: The Journal of Experimental Medicine (2006)

Telomerase is a ribonucleoprotein complex consisting of two essential core components: a reverse transcriptase and an RNA subunit (telomerase RNA [TR]). Dysregulation of telomerase has been associated with cell immortalization and oncogenesis. Marek's disease herpesvirus (MDV) induces a malignant T cell lymphoma in chickens and harbors in its genome two identical copies of a viral TR (vTR) with 88% sequence identity to chicken TR. MDV mutants lacking both copies of vTR were significantly impaired in their ability to induce T cell lymphomas, although lytic replication in vivo was unaffected. Tumor incidences were reduced by &amp;gt;60% in chickens infected with vTR− viruses compared with animals inoculated with MDV harboring at least one intact copy of vTR. Lymphomas in animals infected with the vTR− viruses were also significantly smaller in size and less disseminated. Constitutive expression of vTR in the chicken fibroblast cell line DF-1 resulted in a phenotype consistent with transformation as indicated by morphological alteration, enhanced anchorage-independent cell growth, cell growth beyond saturation density, and increased expression levels of integrin αv. We concluded that vTR plays a critical role in MDV-induced T cell lymphomagenesis. Furthermore, our results provide the first description of tumor-promoting effects of TR in a natural virus–host infection model.
INFECTIOUS FIBROMA OF RABBITS
Authors: Richard E. Shope
Journal: The Journal of Experimental Medicine (1936)

The serial passage of Virus myxomatosum through fibroma-recovered domestic rabbits did not alter its pathogenic properties. Fully virulent Virus myxomatosumpersisted in the inoculated testicle of fibromarecovered rabbits for at least 16 days following inoculation. Virus injected into the testicles of myxoma-immune domestic rabbits, on the other hand, was promptly rendered non-demonstrable. The failure of fibroma-recovered domestic rabbits to destroy injected Virus myxomatosumand the absence from their sera of neutralizing antibodies effective against Virus myxomatosum are considered to be evidence against the identity of the fibroma and myxoma viruses. The rapidity with which fibroma-recovered rabbits develop neutralizing antibodies following infection with Virus myxomatosum is considered to be a possible factor in their acquired resistance. It is believed on the basis of all the evidence that infectious fibroma of rabbits is a definite disease entity and not merely a mild and nonfatal form of infectious myxoma.
Trusts deny health secretary's claims that private finance initiatives have caused major financial problems
Authors: A. O'Dowd
Journal: BMJ (2011)

Several NHS trusts have denied claims by England’s health secretary, Andrew Lansley, that they are facing serious financial problems caused by private finance initiative (PFI) schemes.

A row broke out after Mr Lansley was interviewed and quoted by the Daily Telegraph newspaper on 22 September as saying that he had been contacted by 22 trusts that run more than 60 hospitals between them to raise concerns that their “clinical and financial stability” was under threat because of the costs of their PFI contracts (http://tgr.ph/omk2tO).

However, several of those trusts have now denied the claim, and one said that not only was it in good financial health but that its PFI repayments were factored into financial plans and these were completely “affordable.” 

Mr Lansley’s political opponents have claimed that the figures have been issued to try to distract attention from problems being caused by the government’s controversial changes in the Health and Social Care Bill currently going through Parliament. The list of trusts was put together in April.

Under PFI projects, first introduced by the Conservatives under John Major in 1992 and expanded when Labour came to power in 1997, private companies build hospitals, with …
Systematic documentation and analysis of human genetic variation in hemoglobinopathies using the microattribution approach
Authors: Belinda Giardine, Joseph Borg, Douglas R Higgs, Kenneth R Peterson, Sjaak Philipsen, Donna Maglott, Belinda K Singleton, David J Anstee, A Nazli Basak, Barnaby Clark, Flavia C Costa, Paula Faustino, Halyna Fedosyuk, Alex E Felice, Alain Francina, Renzo Galanello, Monica V E Gallivan, Marianthi Georgitsi, Richard J Gibbons, Piero C Giordano, Cornelis L Harteveld, James D Hoyer, Martin Jarvis, Philippe Joly, Emmanuel Kanavakis, Panagoula Kollia, Stephan Menzel, Webb Miller, Kamran Moradkhani, John Old, Adamantia Papachatzopoulou, Manoussos N Papadakis, Petros Papadopoulos, Sonja Pavlovic, Lucia Perseu, Milena Radmilovic, Cathy Riemer, Stefania Satta, Iris Schrijver, Maja Stojiljkovic, Swee Lay Thein, Jan Traeger-Synodinos, Ray Tully, Takahito Wada, John S Waye, Claudia Wiemann, Branka Zukic, David H K Chui, Henri Wajcman, Ross C Hardison, George P Patrinos
Journal: Nature Genetics (2011)

George Patrinos and colleagues report the first implementation of the microattribution approach to systematically document genetic variation associated with a disease, applied here to hemoglobinopathies and thalassemias. They developed a series of connected locus-specific databases that document genotype and phenotype information for genetic variation in 37 globin and erythroid protein genes in individuals with globin disorders, with reciprocal attribution to data contributors. We developed a series of interrelated locus-specific databases to store all published and unpublished genetic variation related to hemoglobinopathies and thalassemia and implemented microattribution to encourage submission of unpublished observations of genetic variation to these public repositories. A total of 1,941 unique genetic variants in 37 genes, encoding globins and other erythroid proteins, are currently documented in these databases, with reciprocal attribution of microcitations to data contributors. Our project provides the first example of implementing microattribution to incentivise submission of all known genetic variation in a defined system. It has demonstrably increased the reporting of human variants, leading to a comprehensive online resource for systematically describing human genetic variation in the globin genes and other genes contributing to hemoglobinopathies and thalassemias. The principles established here will serve as a model for other systems and for the analysis of other common and/or complex human genetic diseases.
Total and Cancer Mortality After Supplementation With Vitamins and Minerals: Follow-up of the Linxian General Population Nutrition Intervention Trial
Authors: Y.-L. Qiao, S. M. Dawsey, F. Kamangar, J.-H. Fan, C. C. Abnet, X.-D. Sun, L. L. Johnson, M. H. Gail, Z.-W. Dong, B. Yu, S. D. Mark, P. R. Taylor
Journal: JNCI Journal of the National Cancer Institute (2009)

BackgroundThe General Population Nutrition Intervention Trial was a randomized primary esophageal and gastric cancer prevention trial conducted from 1985 to 1991, in which 29 584 adult participants in Linxian, China, were given daily vitamin and mineral supplements. Treatment with "factor D," a combination of 50 μg selenium, 30 mg vitamin E, and 15 mg beta-carotene, led to decreased mortality from all causes, cancer overall, and gastric cancer. Here, we present 10-year follow-up after the end of active intervention.
Bronchial mucosal manifestations of atopy: a comparison of markers of inflammation between atopic asthmatics, atopic nonasthmatics and healthy controls
Authors: R Djukanovic, CK Lai, JW Wilson, KM Britten, SJ Wilson, WR Roche, PH Howarth, ST Holgate
Journal: European Respiratory Journal (1992)

We studied the role of atopy, as defined by positive skin tests to common inhalant allergens, in allergic bronchial inflammation. Endobronchial biopsies were taken via the fibreoptic bronchoscope in 13 symptomatic atopic asthmatics, 10 atopic nonasthmatics, and 7 normals. The numbers of mast cells, identified in the submucosa by immunohistochemistry using the AA1 monoclonal antibody against tryptase, were no different between the three groups, but electron microscopy showed that mast cell degranulation, although less marked in atopic nonasthmatics, was a feature of atopy in general. The numbers of eosinophils, identified by immunohistochemical staining using the monoclonal anti-eosinophil cationic protein antibody, EG2, were greatest in the asthmatics, low or absent in the normals and intermediate in the atopic nonasthmatics. In both atopic groups eosinophils showed ultrastructural features of degranulation. Measurements of subepithelial basement membrane thickness on electron micrographs showed that the collagen layer was thickest in the asthmatics, intermediate in the atopic nonasthmatics and thinnest in the normals. The results suggest that airways eosinophilia and degranulation of eosinophils and mast cells, as well as increased subepithelial collagen deposition, are a feature of atopy in general and suggest that the degree of change may determine the clinical expression of this immune disorder.
The Emerging Role of the Endocannabinoid System in Endocrine Regulation and Energy Balance
Authors: Uberto Pagotto, Giovanni Marsicano, Daniela Cota, Beat Lutz, Renato Pasquali
Journal: Endocrine Reviews (2005)

During the last few years, the endocannabinoid system has emerged as a highly relevant topic in the scientific community. Many different regulatory actions have been attributed to endocannabinoids, and their involvement in several pathophysiological conditions is under intense scrutiny. Cannabinoid receptors, named CB1 receptor and CB2 receptor, first discovered as the molecular targets of the psychotropic component of the plant Cannabis sativa, participate in the physiological modulation of many central and peripheral functions. CB2 receptor is mainly expressed in immune cells, whereas CB1 receptor is the most abundant G protein-coupled receptor expressed in the brain. CB1 receptor is expressed in the hypothalamus and the pituitary gland, and its activation is known to modulate all the endocrine hypothalamic-peripheral endocrine axes. An increasing amount of data highlights the role of the system in the stress response by influencing the hypothalamic-pituitary-adrenal axis and in the control of reproduction by modifying gonadotropin release, fertility, and sexual behavior. The ability of the endocannabinoid system to control appetite, food intake, and energy balance has recently received great attention, particularly in the light of the different modes of action underlying these functions. The endocannabinoid system modulates rewarding properties of food by acting at specific mesolimbic areas in the brain. In the hypothalamus, CB1 receptor and endocannabinoids are integrated components of the networks controlling appetite and food intake. Interestingly, the endocannabinoid system was recently shown to control metabolic functions by acting on peripheral tissues, such as adipocytes, hepatocytes, the gastrointestinal tract, and, possibly, skeletal muscle. The relevance of the system is further strenghtened by the notion that drugs interfering with the activity of the endocannabinoid system are considered as promising candidates for the treatment of various diseases, including obesity.
Trends in Anemia Management among US Hemodialysis Patients
Authors: Joseph A. Coladonato, Diane L. Frankenfield, Donal N. Reddan, Preston S. Klassen, Lynda A. Szczech, Curtis A. Johnson, William F. Owen
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. This study was undertaken to describe the relationship between hematocrit (Hct) and changes in the prescribed dose of erythropoietin (EPO) as well as selected patient and process care measures across annual national samples of hemodialysis patients from 1994 to 1998. This study uses the cohorts identified in the ESRD Core Indicators Project, random samples of 6181, 6241, 6364, 6634, and 7660 patients, stratified by ESRD Networks drawn for each year from 1994 to 1998. Patient demographic and clinical information was collected from October to December for each year. Surrogates of iron stores and patterns of iron and EPO administration were profiled from 1996 to 1998. Multivariable stepwise linear regression analyses were performed to adjust for potential confounding variables and to identify independent variables associated with Hct and EPO dose. Mean Hct and EPO dose increased each year from 31.1 ± 5.2% to 34.1 ± 3.7% and from 58.2 ± 41.8 U/kg to 68.2 ± 55.0 U/kg, respectively ( P = 0.0001). Increasing Hct was positively associated with male gender, more years on dialysis, older age, higher urea reduction ratio and transferrin saturation, prescription of intravenous iron, and lower ferritin and EPO dose in multivariable models (all P = 0.0001). Male gender, older age, diabetes, higher Hct, and increasing weight, urea reduction ration, and transferrin saturation were associated with lower EPO doses (all P &lt; 0.01). Conversely, intravenous EPO and iron were associated with higher prescribed EPO doses (all P = 0.0001). Although increasing Hct is associated with decreasing EPO dose at the patient level, the increase in Hct seen across years among the cohorts of hemodialysis patients in the United States has been associated with increasing doses of EPO at the population level.