tbuckley/cabot-search huggingface dataset:
Human Infection with a Novel Avian-Origin Influenza A (H7N9) Virus
Authors: Rongbao Gao, Bin Cao, Yunwen Hu, Zijian Feng, Dayan Wang, Wanfu Hu, Jian Chen, Zhijun Jie, Haibo Qiu, Ke Xu, Xuewei Xu, Hongzhou Lu, Wenfei Zhu, Zhancheng Gao, Nijuan Xiang, Yinzhong Shen, Zebao He, Yong Gu, Zhiyong Zhang, Yi Yang, Xiang Zhao, Lei Zhou, Xiaodan Li, Shumei Zou, Ye Zhang, Xiyan Li, Lei Yang, Junfeng Guo, Jie Dong, Qun Li, Libo Dong, Yun Zhu, Tian Bai, Shiwen Wang, Pei Hao, Weizhong Yang, Yanping Zhang, Jun Han, Hongjie Yu, Dexin Li, George F. Gao, Guizhen Wu, Yu Wang, Zhenghong Yuan, Yuelong Shu
Journal: New England Journal of Medicine (2013)

Infection of poultry with influenza A subtype H7 viruses occurs worldwide, but the introduction of this subtype to humans in Asia has not been observed previously. In March 2013, three urban residents of Shanghai or Anhui, China, presented with rapidly progressing lower respiratory tract infections and were found to be infected with a novel reassortant avian-origin influenza A (H7N9) virus.We obtained and analyzed clinical, epidemiologic, and virologic data from these patients. Respiratory specimens were tested for influenza and other respiratory viruses by means of real-time reverse-transcriptase-polymerase-chain-reaction assays, viral culturing, and sequence analyses.A novel reassortant avian-origin influenza A (H7N9) virus was isolated from respiratory specimens obtained from all three patients and was identified as H7N9. Sequencing analyses revealed that all the genes from these three viruses were of avian origin, with six internal genes from avian influenza A (H9N2) viruses. Substitution Q226L (H3 numbering) at the 210-loop in the hemagglutinin (HA) gene was found in the A/Anhui/1/2013 and A/Shanghai/2/2013 virus but not in the A/Shanghai/1/2013 virus. A T160A mutation was identified at the 150-loop in the HA gene of all three viruses. A deletion of five amino acids in the neuraminidase (NA) stalk region was found in all three viruses. All three patients presented with fever, cough, and dyspnea. Two of the patients had a history of recent exposure to poultry. Chest radiography revealed diffuse opacities and consolidation. Complications included acute respiratory distress syndrome and multiorgan failure. All three patients died.Novel reassortant H7N9 viruses were associated with severe and fatal respiratory disease in three patients. (Funded by the National Basic Research Program of China and others.).
Risk Factors for Progressive Chronic Kidney Disease
Authors: William M. McClellan, W. Dana Flanders
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. The occurrence of chronic kidney disease and subsequent rate of loss of renal function are highly variable among individuals with the same underlying cause of renal injury or degree of functional impairment. Individual variability of risk is typical of complex diseases and reflects the multifactorial nature of the biologic mechanisms that are involved in the underlying disease process. The utility of the risk factor concept in developing CKD prevention and control strategies includes identifying individuals at high risk for the occurrence and progression of CKD, defining at-risk populations, elucidating potential targets for intervention, and generating explanatory hypotheses for the variable risk of CKD noted in different populations. Future application of the risk factor concept in the prevention and control of CKD will entail developing multivariate prediction equations; using spatial and temporal, as well as personal, characteristics, to define at-risk populations; identifying biomarkers for complex risk factors like race; and translating this information into testable interventions. This should include active extension of our current understanding of health care, social, and economic risk factors at both the individual and the community level. E-mail: [email protected]
Contributions of Plasma Triiodothyronine and Local Thyroxine Monodeiodination to Triiodothyronine to Nuclear Triiodothyronine Receptor Saturation in Pituitary, Liver, and Kidney of Hypothyroid Rats
Authors: J. E. Silva, P. R. Larsen
Journal: Journal of Clinical Investigation (1978)

Injections of triiodothyronine (T3) and thyroxine (T4) into chronically hypothyroid rats were used to evaluate the contribution of intracellular T4 to T3 conversion to nuclear T3 in pituitary, liver, and kidney, and to correlate the occupancy of pituitary nuclear T3 receptors with inhibition of thyroid-stimulating hormone (TSH) release. Injection of a combination of 70 ng T3 and 400 ng T4/100 g body wt resulted in plasma T3 concentrations of 45±7 ng/dl (mean±SD) and 3.0±0.4 μg/dl T4 3 h later. At that plasma T3 level, the contribution of plasma T3 to the nuclear receptor sites resulted in saturation of 34±7% for pituitary, 27±5% for liver, and 33±2% for kidney. In addition to the T3 derived from plasma T3, there was additional T3 derived from intracellular monodeiodination of T4 in all three tissues that resulted in total nuclear occupancy (as percent saturation) of 58±11% (pituitary), 36±8% (liver), and 41±11% (kidney), respectively. The percent contribution of T3 derived from cellular T4 added 41% of the total nuclear T3 in the pituitary which was significantly higher than the contribution of this source in the liver (24%) or the kidney (19%). 3 h after intravenous injection of increasing doses of T3, the plasma T3 concentration correlated well with both the change in TSH and the nuclear occupancy, suggesting a linear relationship between the integrated nuclear occupancy by T3 and TSH release rate. The contribution of intrapituitary T4 to T3 conversion to nuclear T3 was accompanied by an appropriate decrease in TSH, supporting the biological relevance of nuclear T3. Pretreatment of the animals with 6-n-propylthiouracil before T4 injection decreased neither the nuclear T3 derived from intrapituitary T4 nor the subsequent decrease in TSH.
Evaluating the effects of stress on asthma: a paradoxical challenge
Authors: M.D. Klinnert
Journal: European Respiratory Journal (2003)

Investigations into the relationship between emotional stress and asthma have a long and complicated history. Stemming from patient reports and clinician observations that asthma exacerbations were sometimes preceded by emotional reactions or severe stress, a series of empirical investigations was initiated in the 1960s. Study results were inconsistent, with some apparently methodologically rigorous studies showing relationships between emotional arousal and lung function changes, while others were unable to demonstrate such effects 1. In the face of this confusing picture, a number of reviews have attempted to integrate data from the field, and in so doing have proposed pathways and mechanisms to explain how emotions or stress could affect asthma 1–4. From the beginning, this area of research has been plagued by the paradox wherein the typical physiological reaction to emotional arousal was the opposite of physiological events associated with bronchoconstriction. The paper by Laube et al. 5 in the current issue of the European Respiratory Journal , which describes careful testing of a hypothesis generated by a theoretical model, represents another step forward in this tortuous process of investigation. Although the authors' hypothesis was not supported, the specifics of the unexpected results of the study provide another piece of the puzzle, and so contribute to a revision and refinement of the working model for investigating the interaction of stress and asthma.

The most important aspect of the results reported by laube et al. 5 was the failure of the data to support the hypothesis; in fact, the results were the opposite of what was expected. The authors hypothesised that the pulmonary response toallergen exposure in individuals with allergic asthma would be potentiated by emotional arousal elicited by a stress interview. Instead, lung function testing showed less airway …
Preemptive use of lamivudine reduces hepatitis B exacerbation after allogeneic hematopoietic cell transplantation
Authors: George K. K. Lau, Ming-Liang He, Daniel Y. T. Fong, Angeline Bartholomeusz, Wing-yan Au, Albert K. W. Lie, Stephen Locarnini, Raymond Liang
Journal: Hepatology (2002)

Exacerbation of hepatitis B virus (HBV) is a serious cause of morbidity and mortality in hepatitis B surface antigen (HBsAg)-positive patients undergoing transplantation. Our aim was to evaluate the effectiveness of lamivudine to prevent hepatitis due to exacerbation of HBV in HBsAg-positive patients treated with allogeneic hematopoietic cell transplantation. We studied 20 consecutive HBsAg-positive recipients of allogeneic hematopoietic cell transplantation who received lamivudine 100 mg daily starting one week before transplantation until week 52 after transplantation (group 1). Serial serum alanine aminotransferase and HBV DNA levels were measured before and after transplantation at 4- to 8-week intervals for the first year and then 4- to 12-week intervals. Their virologic and clinical outcomes were compared with 20 case-matched recipients who did not receive any antiviral therapy to HBV (anti-HBV) before and after hematopoietic cell transplantation (group 2). After transplantation, 9 patients (45%) in group 2 and one patient (5%) in group 1 had hepatitis due to exacerbation of HBV ( P &lt; .008), with 3 hepatic failures in group 2 and none in group 1. The one-year actuarial probability of survival without hepatitis due to exacerbation of HBV was higher in group 1 than group 2 (94.1% vs. 54.3%, P = .002). By multivariate Cox analysis, preemptive use of lamivudine effectively reduced hepatitis due to exacerbation of HBV (adjusted hazards ratio, 0.09; P = .021). In conclusion, preemptive lamivudine reduced HBV exacerbation. The use of lamivudine with other immunosuppressive regimens to prevent exacerbation of HBV should be further explored.
Metabolic and calcium kinetic studies in idiopathic hypercalciuria
Authors: U. A. Liberman, O. Sperling, A. Atsmon, M. Frank, M. Modan, A. De Vries
Journal: Journal of Clinical Investigation (1968)

Calcium balances and calcium kinetic studies using 47Ca were performed in nine male patients with idiopathic hypercalciuria and in three normal male subjects. A sharp reduction in calcium intake in eight patients with idiopathic hypercalciuria caused a decrease in urinary calcium excretion, the latter remaining elevated above that reported for normal subjects on a low calcium diet. The hypercalciuric patients had an enlarged miscible calcium pool size, an increased calcium turnover rate, increased bone formation and bone resorption rates, and an elevated true intestinal calcium absorption rate, the increase of the latter three parameters being proportional to the increase of the turnover rate. The fraction of the calcium turnover rate excreted in the urine was elevated whereas that constituted by the endogenous fecal calcium excretion was decreased. Arguments are presented for the concept that the primary abnormality in idiopathic hypercalciuria is neither renal calcium hyperexcretion nor intestinal calcium hyperreabsorption, but a more fundamental disturbance in calcium metabolism of as yet unknown cause, leading to a high calcium turnover.
Heparin-Bonded Covered Stents Versus Bare-Metal Stents for Complex Femoropopliteal Artery Lesions
Authors: Johannes Lammer, Thomas Zeller, Klaus A. Hausegger, Philipp J. Schaefer, Manfred Gschwendtner, Stefan Mueller-Huelsbeck, Thomas Rand, Martin Funovics, Florian Wolf, Aljoscha Rastan, Michael Gschwandtner, Stefan Puchner, Robin Ristl, Maria Schoder
Journal: Journal of the American College of Cardiology (2013)
Human Tumor-Derived Exosomes Selectively Impair Lymphocyte Responses to Interleukin-2
Authors: Aled Clayton, J. Paul Mitchell, Jacquelyn Court, Malcolm D. Mason, Zsuzsanna Tabi
Journal: Cancer Research (2007)

Abstract Exosomes are nanometer-sized vesicles, secreted by normal and neoplastic cells. The outcome following interaction between the cellular immune system and cancer-derived exosomes is not well understood. Interleukin-2 (IL-2) is a key factor supporting expansion and differentiation of CTL and natural killer (NK) cells but can also support regulatory T cells and their suppressive functions. Our study examined whether tumor-derived exosomes could modify lymphocyte IL-2 responses. Proliferation of healthy donor peripheral blood lymphocytes in response to IL-2 was inhibited by tumor exosomes. In unfractionated lymphocytes, this effect was seen in all cell subsets. Separating CD4+ T cells, CD8+ T cells, and NK cells revealed that CD8+ T-cell proliferation was not inhibited in the absence of CD4+ T cells and that NK cell proliferation was only slightly impaired. Other exosome effects included selective impairment of IL-2–mediated CD25 up-regulation, affecting all but the CD3+CD8− T-cell subset. IL-2–induced Foxp3 expression by CD4+CD25+ cells was not inhibited by tumor exosomes, and the suppressive function of CD4+CD25+ T cells was enhanced by exosomes. In contrast, exosomes directly inhibited NK cell killing function in a T-cell–independent manner. Analysis of tumor exosomes revealed membrane-associated transforming growth factor β1 (TGFβ1), which contributed to the antiproliferative effects, shown by using neutralizing TGFβ1-specific antibody. The data show an exosome-mediated mechanism of skewing IL-2 responsiveness in favor of regulatory T cells and away from cytotoxic cells. This coordinated “double hit” to cellular immunity strongly implicates the role of exosomes in tumor immune evasion. [Cancer Res 2007;67(15):7458–66]
Analysis of MAdCAM-1 and ICAM-1 polymorphisms in 365 Scandinavian patients with primary sclerosing cholangitis
Authors: Christopher L. Bowlus, Tom H. Karlsen, Ulrika Broomé, Erik Thorsby, Morten Vatn, Erik Schrumpf, Benedicte A. Lie, Kirsten Muri Boberg
Journal: Journal of Hepatology (2006)
Update in <i>Mycobacterium tuberculosis</i> Lung Disease 2014
Authors: Paul Elkington, Alimuddin Zumla
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

The global tuberculosis (TB) pandemic continues despite intensive TB control and research efforts.Research articles related on Mycobacterium tuberculosis (M.tb) infection published in the Journal focused on five main areas: basic science, evaluation of novel diagnostics, epidemiology, transmission, and clinical trials.These range from exciting developments in new compounds to treat multidrug-resistant (MDR)-TB to major disappointments from clinical trials evaluating new treatment-shortening regimens and vaccine efficacy studies.We review these publications and discuss developments and approaches that may maximize improved TB management.
Transmission of malaria to mosquitoes blocked by bumped kinase inhibitors
Authors: Kayode K. Ojo, Claudia Pfander, Natascha R. Mueller, Charlotte Burstroem, Eric T. Larson, Cassie M. Bryan, Anna M.W. Fox, Molly C. Reid, Steven M. Johnson, Ryan C. Murphy, Mark Kennedy, Henning Mann, David J. Leibly, Stephen N. Hewitt, Christophe L.M.J. Verlinde, Stefan Kappe, Ethan A. Merritt, Dustin J. Maly, Oliver Billker, Wesley C. Van Voorhis
Journal: Journal of Clinical Investigation (2012)

Effective control and eradication of malaria will require new tools to prevent transmission. Current antimalarial therapies targeting the asexual stage of Plasmodium do not prevent transmission of circulating gametocytes from infected humans to mosquitoes. Here, we describe a new class of transmission-blocking compounds, bumped kinase inhibitors (BKIs), which inhibit microgametocyte exflagellation. Oocyst formation and sporozoite production, necessary for transmission to mammals, were inhibited in mosquitoes fed on either BKI-1-treated human blood or mice treated with BKI-1. BKIs are hypothesized to act via inhibition of Plasmodium calcium-dependent protein kinase 4 and predicted to have little activity against mammalian kinases. Our data show that BKIs do not inhibit proliferation of mammalian cell lines and are well tolerated in mice. Used in combination with drugs active against asexual stages of Plasmodium, BKIs could prove an important tool for malaria control and eradication.
Effect of moderate exercise on bowel habit.
Authors: G J Oettle
Journal: Gut (1991)

Ten healthy volunteers (six men and four women, aged 22-41 years) were studied in a crossover trial. The study was divided into three one week periods. During each period the subjects either ran on a treadmill, cycled on a bicycle ergometer, or rested in a chair for 1 hour every day. The exercise was performed at two thirds predicted maximum heart rate (equivalent to 50% VO2 max). The sequences were rotated; no studies were performed in the perimenstrual period. Transit was measured by the method of measuring the excretion of a single dose of radio-opaque markers; all stools were collected, weighed, and x rayed after the ingestion of radio-opaque markers. Dietary fibre and fluid intake were measured on the fourth day of each test period by 24 hour record. Lifestyle was otherwise unchanged. Transit time was dramatically accelerated by moderate exercise (both jogging and cycling); however, stool weight, defecation frequency, dietary fibre intake, and fluid intake did not change significantly. Whole gut transit changed from 51.2 hours (95% confidence intervals 41.9 to 60.5) at rest to 36.6 hours (31.6 to 39.2) when riding and 34.0 hours (28.8 to 39.2) when jogging. Riding and running both differed significantly from resting (p less than 0.01); the difference between riding and running was not significant.
Extra-articular disease manifestations in rheumatoid arthritis: incidence trends and risk factors over 46 years
Authors: Carl Turesson, WM O'Fallon, CS Crowson, SE Gabriel, EL Matteson
Journal: Annals of the Rheumatic Diseases (2003)

To investigate the trends in incidence of extra-articular rheumatoid arthritis (ExRA) in a well defined community based cohort of patients with rheumatoid arthritis (RA), and to examine possible predictors of ExRA occurrence.Using the resources of the Rochester Epidemiology Project, a retrospective medical record review was conducted of a cohort of 609 cases of RA in Olmsted County, MN, diagnosed during 1955-94. These cases had been previously classified using the ACR 1987 criteria for RA. Patients were followed up from 1955 to 2000 (median follow up 11.8 years; range 0.1-42.8), and incident ExRA manifestations were recorded according to predefined criteria. Time to first presentation of ExRA was compared in patients with RA by decade of diagnosis. Possible ExRA risk factors were identified in case record reviews.ExRA occurred in 247 patients (40.6%). A subgroup of 78 patients (12.8%) had ExRA manifestations considered to be severe in a previous study from Malmö, Sweden. The incidence of severe ExRA did not change significantly over the decades (p=0.165). In a multivariate analysis the main predictors of severe ExRA were smoking at RA diagnosis (risk ratio (RR)=2.94; 95% confidence interval (95% CI) 1.68 to 5.13) and early disability (Steinbrocker class III-IV at diagnosis) (RR=2.45; 95% CI 1.51 to 4.00). The effect of smoking overwhelmed the weaker effect of rheumatoid factor seropositivity.There was no decrease in the incidence of extra-articular manifestations in patients with RA diagnosed up to 1995. Smoking and early disability are independent risk factors for extra-articular RA.
IL-10 blockade facilitates DNA vaccine-induced T cell responses and enhances clearance of persistent virus infection
Authors: David G. Brooks, Andrew M. Lee, Heidi Elsaesser, Dorian B. McGavern, Michael B.A. Oldstone
Journal: The Journal of Experimental Medicine (2008)

Therapeutic vaccination is a potentially powerful strategy to establish immune control and eradicate persistent viral infections. Large and multifunctional antiviral T cell responses are associated with control of viral persistence; however, for reasons that were mostly unclear, current therapeutic vaccination approaches to restore T cell immunity and control viral infection have been ineffective. Herein, we confirmed that neutralization of the immunosuppressive factor interleukin (IL)-10 stimulated T cell responses and improved control of established persistent lymphocytic choriomeningitis virus (LCMV) infection. Importantly, blockade of IL-10 also allowed an otherwise ineffective therapeutic DNA vaccine to further stimulate antiviral immunity, thereby increasing T cell responses and enhancing clearance of persistent LCMV replication. We therefore propose that a reason that current therapeutic vaccination strategies fail to resurrect/sustain T cell responses is because they do not alleviate the immunosuppressive environment. Consequently, blocking key suppressive factors could render ineffective vaccines more efficient at improving T cell immunity, and thereby allow immune-mediated control of persistent viral infection.
Complications of high translumbar aortography.
Authors: P Davies
Journal: BMJ (1977)

grey and breathless in her cot.A tachycardia of 240/min was noted which settled over the following four hours.Examination showed no evidence of cardiac failure.A chest x-ray was normal.An ECG the next morning revealed a sinus tachycardia of 180, min.Her subsequent progress was unevent- ful and she was discharged home on her 65th day weighing 2 42 kg.She failed to keep her follow-up appointmmnt and we later learnt that she had been found dead in her cot unexpectedly at home at the age of 10 weeks.Post-mortem examination revealed no abnormalities.
A comparison of asthma deaths and near-fatal asthma attacks in South Australia
Authors: DA Campbell, G McLennan, None Coates, PA Frith, PA Gluyas, KM Latimer, CG Luke, AJ Martin, DM Roder, RE Ruffin, al. et
Journal: European Respiratory Journal (1994)

Studies seeking to identify factors predictive of asthma mortality have relied on information obtained from relatives, other close acquaintances, and doctors who cared for the deceased. We wanted to determine whether asthmatics who have suffered a near-fatal asthma attack (NFA) are similar to asthmatics who have died of asthma with respect to important features, because studies of NFA asthmatics may provide a better insight into causes of asthma death. Such studies would avoid the difficulties associated with seeking information secondhand from proxy informants. Two groups were studied: asthmatics who had suffered a near-fatal asthma attack resulting in a visit to the accident and emergency departments of teaching hospitals (n = 154), and asthmatics certified as dying of asthma who, following panel review, were confirmed to have died from this disease (n = 80). For each case in the two groups, an interview questionnaire was administered to a close acquaintance (household or family member) and to the general practitioner. Both groups shared many important characteristics. Similarities related to: frequency of symptoms; frequency of hospital and intensive care unit admissions for asthma; use of asthma crisis plans; compliance with prescribed medications; quality of personal asthma management; and asthma severity. The two groups also showed similar psychiatric profiles, and similar use of asthma medications on a regular basis and with increased symptoms. However, NFA cases tended to be younger, were more likely to be male, and less likely to have concurrent medical conditions.(ABSTRACT TRUNCATED AT 250 WORDS)