tbuckley/cabot-search huggingface dataset:
Functional interleukin-2 receptors on intestinal epithelial cells.
Authors: C Ciacci, Y R Mahida, A Dignass, M Koizumi, D K Podolsky
Journal: Journal of Clinical Investigation (1993)

The presence of receptors for the cytokine IL-2 was assessed in the IEC-6 cell line established from normal rat crypt epithelium and primary intestinal epithelial cells. 125I-IL-2 was found to specifically bind to subconfluent IEC-6 cells. Maximal binding was observed within 30 min after addition of the ligand; binding could be inhibited by excess unlabeled IL-2 or addition of antibody to the IL-2 receptor. Both intermediate and low affinity receptors with approximate Kd of 10 and 100 pM, respectively were present. Kinetic analysis were consistent with the results of Western blot analysis using an antisera to the 75-kD IL-2 receptor beta chain. IL-2 receptors appeared to be functional; addition of IL-2 led to modulation of proliferation with initial stimulation at 24 h followed by inhibition at 48 h. This effect could be blocked by addition of antibody to the IL-2 receptor beta chain. IL-2 treatment could be shown to enhance expression (range = 4- to 50-fold stimulation) of TGF-beta, as well as the lectin protein mac-2, in IEC-6 cells. The relevance of observations in the IEC-6 cell line to intestinal mucosa in vivo was supported by the demonstration of a gradient of expression of the IL-2 receptor in primary rat intestinal epithelial cells by Western blot analysis. In addition, mRNA for the IL-2 receptor-beta chain was demonstrated by Northern blot analysis using mRNA from primary rat intestinal epithelial cells depleted of detectable contaminating intraepithelial lymphocytes by two cycles of fractionation on Percoll gradients. Collectively, these observations suggest that the range of cellular targets of the putative lymphokine IL-2 is broader than appreciated, and IL-2 may serve to integrate epithelial and lymphocyte responses in the intestinal mucosa.
Renal Transplantation Modulates Expression and Function of Receptors and Transporters of Rat Proximal Tubules
Authors: Ana Velic, Jochen R. Hirsch, Jasmin Bartel, Regina Thomas, Rita Schröter, Heike Stegemann, Bayram Edemir, Christian August, Eberhard Schlatter, Gert Gabriëls
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Kidney transplantation often leads to disturbances of solute and volume maintenance in humans. To investigate underlying mechanisms, expression and function of renal transporters and receptors of the proximal tubule (PT) were analyzed in an acute rejection model of rat kidney transplantation. Semiquantitative RT-PCR and Western blot, histology, immunohistochemistry, and microfluorometry were performed on whole kidneys and isolated PT. With acute rejection, Na+/H+-exchanger type-3 (NHE-3) was markedly downregulated. Na+-HCO3−-cotransporter (NBC-1) and Na+-glucose transporter type-2 (SGLT2) were upregulated after transplantation. Expressions of Na+/H+-exchanger type-1 (NHE-1), Na+/K+-ATPase (NKA), angiotensin II (AngII) receptor (AT-1), or natriuretic peptide receptor (GC-A) were unaltered. Microfluorometric analyses of intracellular pH, Na+, and Ca2+ demonstrated a decrease in NHE-3 function and AngII-mediated stimulation of NHE-3. AngII-mediated inhibition of NHE-1 and function of all other transporters tested remained unaltered. Function of AT-1 and GC-A were unaffected. Reduced expression of NHE-3 was also confirmed by semiquantitative immunohistochemistry. These findings suggest that expression and function of transmembrane proteins involved in Na+-transport after transplantation and rejection is specifically modulated. The local renin-angiotensin-system is apparently not altered. Downregulation of NHE-3 may be a protective mechanism occurring in the graft.
Long-term clinical and cost-effectiveness of psychological intervention for family carers of people with dementia: a single-blind, randomised, controlled trial
Authors: Gill Livingston, Julie Barber, Penny Rapaport, Martin Knapp, Mark Griffin, Derek King, Renee Romeo, Debbie Livingston, Cath Mummery, Zuzana Walker, Juanita Hoe, Claudia Cooper
Journal: The Lancet Psychiatry (2014)

Two-thirds of people with dementia live at home supported mainly by family carers. These carers frequently develop clinical depression or anxiety, which predicts care breakdown. We aimed to assess the clinical effectiveness (long-term reduction of depression and anxiety symptoms in family carers) and cost-effectiveness of a psychological intervention called START (STrAtegies for RelaTives).We did a randomised, parallel-group trial with masked outcome assessments in three UK mental-health services and one neurological-outpatient dementia service. We included self-identified family carers of people with dementia who had been referred in the previous year and gave support at least once per week to the person with dementia. We randomly assigned these carers, via an online computer-generated randomisation system from an independent clinical trials unit, to either START, an 8-session, manual-based coping intervention delivered by supervised psychology graduates, or treatment as usual (TAU). The primary long-term outcomes were affective symptoms (Hospital Anxiety and Depression Scale total score [HADS-T]) 2 years after randomisation and cost-effectiveness (health and social care perspectives) over 24 months. Analysis was by intention to treat, excluding carers with data missing at both 12 and 24 months. This trial is registered ISCTRN70017938.From November 4, 2009, to June 8, 2011, we recruited 260 carers. 173 carers were randomly assigned to START and 87 to TAU. Of these 260 participants, 209 (80%) were included in the clinical efficacy analysis (140 START, 69 TAU). At 24 months, compared with TAU the START group was significantly better for HADS-T (mean difference -2·58 points, 95% CI -4·26 to -0·90; p=0·003). The intervention is cost effective for both carers and patients (67% probability of cost-effectiveness at the £20 000 per QALY willingness-to-pay threshold, and 70% at the £30 000 threshold).START is clinically effective, improving carer mood and anxiety levels for 2 years. Carers in the control TAU group were seven times more likely to have clinically significant depression than those receiving START. START is cost effective with respect to carer and patient outcomes, and National Institute for Health and Care Excellence (NICE) thresholds. The number of people with dementia is rapidly growing, and policy frameworks assume that their families will remain the frontline providers of (unpaid) support. This cost-neutral intervention, which substantially improves family-carers' mental health and quality of life, should therefore be widely available.National Institute for Health Research Health Technology Assessment programme 08/14/06.
Assessment of Aortic Pulse Wave Velocity and Cardiac Diastolic Function in Subjects With and Without the Metabolic Syndrome
Authors: Stijntje D. Roes, Reza Alizadeh Dehnavi, Jos J.M. Westenberg, Hildo J. Lamb, Bart J.A. Mertens, Jouke T. Tamsma, Albert de Roos
Journal: Diabetes Care (2008)

To evaluate the influence of lipid and glucose metabolism in the metabolic syndrome on aortic pulse wave velocity (PWV) and left ventricular (LV) diastolic function using magnetic resonance imaging (MRI).
Reduced Systolic Myocardial Function in Children with Chronic Renal Insufficiency
Authors: Marcello Chinali, Giovanni de Simone, Maria Chiara Matteucci, Stefano Picca, Antonio Mastrostefano, Ali Anarat, Salim C[COMBINING CEDILLA]aliskan, Nikola Jeck, Thomas J. Neuhaus, Amira Peco-Antic, Licia Peruzzi, Sara Testa, Otto Mehls, Elke Wühl, Franz Schaefer
Journal: Journal of the American Society of Nephrology (2007)

Increased left ventricular (LV) mass in children with chronic renal insufficiency (CRI) might be adaptive to sustain myocardial performance in the presence of increased loading conditions. It was hypothesized that in children with CRI, LV systolic function is impaired despite increased LV mass (LVM). Standard echocardiograms were obtained in 130 predialysis children who were aged 3 to 18 yr (59% boys) and had stages II through IV chronic kidney disease and in 130 healthy children of similar age, gender distribution, and body build. Systolic function was assessed by measurement of fractional shortening at the endocardial (eS) and midwall (mS) levels and computation of end-systolic stress (myocardial afterload). The patients with CRI exhibited a 6% lower eS (33.1 +/- 5.5 versus 35.3 +/- 6.1%; P < 0.05) and 10% lower mS (17.8 +/- 3.1 versus 19.7 +/- 2.7%; P < 0.001) than control subjects in the presence of significantly elevated BP, increased LVM, and more concentric LV geometry. Whereas the decreased eS was explained entirely by augmented end-systolic stress, mS remained reduced after correction for myocardial afterload. The prevalence of subclinical systolic dysfunction as defined by impaired mS was more than five-fold higher in patients with CRI compared with control subjects (24.6 versus 4.5%; P < 0.001). Systolic dysfunction was most common (48%) in patients with concentric hypertrophy and associated with lower hemoglobin levels. CRI in children is associated with impaired intrinsic LV contractility, which parallels increased LVM.
Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial
Authors: John JV McMurray, Jan Östergren, Karl Swedberg, Christopher B Granger, Peter Held, Eric L Michelson, Bertil Olofsson, Salim Yusuf, Marc A Pfeffer
Journal: The Lancet (2003)
Prevalence of symptoms of Raynaud's phenomenon in general practice.
Authors: A Silman, S Holligan, P Brennan, P Maddison
Journal: BMJ (1990)

To investigate the prevalence of Raynaud's phenomenon in the populations of five general practices.Two populations studied. A questionnaire was given to all new patients attending five general practices over four weeks, and the same questionnaire was sent by post to a random sample of adults from two of the practices.General practices in inner London, Merseyside, and Cheshire.1532 Patients who completed questionnaires (1119 who attended the surgeries (response rate unknown) and 413 respondents to the postal survey (response rate 69%)).Response to questionnaire on symptoms of Raynaud's phenomenon: patients were regarded as having the disease if they had episodes of blanching of the fingers that were precipitated by cold and accompanied by sensory symptoms (pins and needles or numbness). Subsequent interview and clinical appraisal of patients with the disease according to their responses to the questionnaire.The prevalence of Raynaud's phenomenon was 11% (26/231) and 19% (34/182) respectively in men and women who completed the postal questionnaire and 16% (56/357) and 21% (157/762) respectively in those who completed the questionnaire when attending their general practice. Thus the overall rates were slightly higher in women, but there was no effect of age even after adjustment of the rates for practice and method of survey.The prevalence of Raynaud's phenomenon is high compared with the low number of patients who seek treatment for the disease.
Different capacities for amino acid transport in periportal and perivenous hepatocytes isolated by digitonin/collagenase perfusion†
Authors: Hans-Jörg Burger, Rolf Gebhardt, Claus Mayer, Dieter Mecke
Journal: Hepatology (1989)

Periportal and perivenous hepatocytes were isolated from rat liver by digitonin/collagenase perfusion for investigating the acinar heterogeneity of amino acid transport activities related to glutamine and ammonia metabolism. Immunocytochemical staining of the respective subpopulations for glutamine synthetase demonstrated that periportal subpopulations were essentially free of glutamine synthetase-positive cells, whereas perivenous subpopulations showed a 2- to 3- fold enrichment of glutamine synthetase-positive hepatocytes. The high perivenous/periportal ratio of 59 found for glutamine synthetase activity as well as the perivenous/periportal ratios of other marker enzymes further indicated the good separation of periportal and perivenous cells. α-Aminoisobutyric acid, histidine and glutamate were used to determine the distribution pattern of amino acid transport systems A, N and G − , as well as of the sodium-independent uptake of these compounds 1 hr after isolation and after maximal hormonal stimulation during primary culture. The strong heterogeneity of the sodium-independent transport of histidine, characterized by higher perivenous transport rates [perivenous/periportal ratio: 1.5 (1 hr) to 3.5 (48 hr)], suggests a significant role of facilitated diffusion, presumably in glutamine export. Conversely, the strong heterogeneity of the sodium-dependent glutamate transport (System G − ) characterized by higher uptake rates in nonstimulated [perivenous/periportal ratio: 6.6 (1 hr)] and in hormonally treated perivenous hepatocytes (perivenous/periportal ratio: 2.2) reflects its possible significance with respect to the substrate availability for glutamine synthesis. The observed heterogeneities provide a basis for understanding how substrate fluxes related to glutamine metabolism might be established and regulated. In addition, our findings indicate that periportal and perivenous cells retain their zonal characteristics with respect to amino acid transport in primary culture for at least 48 hr.
New Concepts in Chronic Obstructive Pulmonary Disease
Authors: Peter J. Barnes
Journal: Annual Review of Medicine (2003)

Chronic obstructive pulmonary disease (COPD) is a leading cause of death and disability but has only recently been explored from a cellular and molecular perspective. In COPD, chronic inflammation leads to fixed narrowing of small airways and alveolar wall destruction (emphysema). This is characterized by increased numbers of alveolar macrophages, neutrophils, and cytotoxic T lymphocytes, and the release of multiple inflammatory mediators (lipids, chemokines, cytokines, growth factors). There is also a high level of oxidative stress, which may amplify this inflammation. There is increased elastolysis and probable involvement of matrix metalloproteinases. The inflammation and proteolysis in COPD is an amplification of the normal inflammatory response to cigarette smoke. Unlike asthma, this inflammation appears to be resistant to corticosteroids, prompting a search for novel anti-inflammatory therapies that may prevent the relentless progression of the disease.
Association of IL33–IL-1 receptor–like 1 (IL1RL1) pathway polymorphisms with wheezing phenotypes and asthma in childhood
Authors: Olga E. Savenije, Jestinah M. Mahachie John, Raquel Granell, Marjan Kerkhof, F. Nicole Dijk, Johan C. de Jongste, Henriëtte A. Smit, Bert Brunekreef, Dirkje S. Postma, Kristel Van Steen, John Henderson, Gerard H. Koppelman
Journal: Journal of Allergy and Clinical Immunology (2014)
Cost-effectiveness of 3 Methods to Enhance the Sensitivity of Papanicolaou Testing
Authors: Adalsteinn D. Brown, Alan M. Garber
Journal: JAMA (1999)

ThinPrep, AutoPap, and Papnet are 3 new technologies that increase the sensitivity and cost of cervical cancer screening.To estimate the cost-effectiveness of these technological enhancements to Papanicolaou (Pap) tests.We estimated the increase in sensitivity from using these technologies by combining results of 8 studies meeting defined criteria. We used published literature and additional sources for cost estimates. To estimate overall cost-effectiveness, we applied a 9-state time-varying transition state model to these data and information about specific populations.A hypothetical program serving a cohort of 20- to 65-year-old women who begin screening at the same age and are representative of the US population.The new technologies increased life expectancy by 5 hours to 1.6 days, varying with the technology and the frequency of screening. All 3 technologies also increased the cost per woman screened by $30 to $257 (1996 US dollars). AutoPap dominated ThinPrep in the base case. At each screening interval, AutoPap increased survival at the lowest cost. The cost per year of life saved rose from $7777 with quadrennial screening to $166000 with annual screening. Papnet produced more life-years at a higher cost per year of life saved. However, when used with triennial screening, each of them produced more life-years at lower cost than conventional Pap testing every 2 years. The cost-effectiveness ratio of each technology improved with increases in the prevalence of disease, decreases in the sensitivity of conventional Pap testing, and increases in the improvement in sensitivity produced by the technology.Technologies to increase the sensitivity of Pap testing are more cost-effective when incorporated into infrequent screening. Increases in sensitivity and decreases in cost may eventually make each technology more cost-effective.
Abnormal membrane protein of red blood cells in hereditary spherocytosis
Authors: H. S. Jacob, A. Ruby, E. S. Overland, D. Mazia
Journal: Journal of Clinical Investigation (1971)

We present evidence that the hereditable hemolytic disease, hereditary spherocytosis (HS), involves an abnormality in protein of the red cell membrane. Unlike that from normal red cells, lipid-free proteins extracted from HS red cell membranes fail to increase in sedimentation rate when treated with cations; such treatment of normal membrane proteins has been shown by others to cause the formation of microfilaments. That microfilament formation might be defective in HS red cell membranes is supported by observations with vinblastine. This compound, a potent precipitant of filamentous, structure proteins throughout phylogeny, precipitates significantly less HS membrane protein than normal. The resistance of HS membrane protein to changes in conformation by cations is observable at the cellular level as well. That is, both normal and HS red cells agglutinate after repeated washing and suspension in electrolyte-free media. Tiny concentrations of Ca(++) (5 x 10(-5) M) changes the surfaces of normal cells in such a way as to cause disagglutination; HS red cells resist this change and remain agglutinated unless Ca(++) concentrations are increased many-fold. We conclude that membrane ("structure") proteins of HS red cells are genetically altered in such a way as to interfere with their proper conformation, perhaps into fibrils. Potentially many mutations in membrane proteins might preclude this alignment, with the result that normal erythrocyte biconcavity and plasticity is prevented and the clinical syndrome of hereditary spherocytosis is manifest.
VIII: Meta-Analysis of the Efficacy of Vitamin D Treatment in Preventing Osteoporosis in Postmenopausal Women
Authors: Emmanuel Papadimitropoulos, George Wells, Beverley Shea, William Gillespie, Bruce Weaver, Nicole Zytaruk, Ann Cranney, Jonathan Adachi, Peter Tugwell, Robert Josse, Carol Greenwood, Gordon Guyatt
Journal: Endocrine Reviews (2002)

Objective: To review the effect of vitamin D on bone density and fractures in postmenopausal women.Data Source: We searched MEDLINE and EMBASE from 1966 to 1999 and examined citations of relevant articles and proceedings of international meetings.We contacted osteoporosis investigators and primary authors to identify additional studies and to obtain unpublished data.Study Selection: We included 25 trials that randomized women to standard or hydroxylated vitamin D with or without calcium supplementation or a control and measured bone density or fracture incidence for at least 1 yr.Data Extraction: For each trial, three independent reviewers assessed the methodological quality and abstracted data.Data Synthesis: Vitamin D reduced the incidence of vertebral fractures [relative risk (RR) 0.63, 95% confidence interval (CI) 0.45-0.88,P Ͻ 0.01) and showed a trend toward reduced incidence of nonvertebral fractures (RR 0.77, 95% CI 0.57-1.04,P ϭ 0.09).Most patients in the trials that evaluated vertebral fractures received hydroxylated vitamin D, and most patients in the trials that evaluated nonvertebral fractures received standard vitamin D.Hydroxylated vitamin D had a consistently larger impact on bone density than did standard vitamin D. For instance, total body differences in percentage change between hydroxylated vitamin D and control were 2.06 (0.72, 3.40) and 0.40 (Ϫ0.25, 1.06) for standard vitamin D. At the lumbar spine and forearm sites, hydroxylated vitamin D doses above 50 g yield larger effects than lower doses.Vitamin D resulted in an increased risk of discontinuing medication in comparison to control as a result of either symptomatic adverse effects or abnormal laboratory results (RR 1.37, 95% CI 1.01-1.88),an effect that was similar in trials of standard and hydroxylated vitamin D.Conclusions: Vitamin D decreases vertebral fractures and may decrease nonvertebral fractures.The available data are uninformative regarding the relative effects of standard and hydroxylated vitamin D.
Autoantibodies to HLA B27 in the sera of HLA B27 patients with ankylosing spondylitis and Reiter's syndrome. Molecular mimicry with Klebsiella pneumoniae as potential mechanism of autoimmune disease.
Authors: P L Schwimmbeck, D T Yu, M B Oldstone
Journal: The Journal of Experimental Medicine (1987)

Ankylosing spondylitis (AS) and Reiter's syndrome (RS) both show a strong correlation with the HLA B27 haplotype. We studied whether sharing of homologous amino acid sequences in the HLA B27 antigen with an invading microbe might occur, and if so, what is the biological significance of such homology. In a computer search of the Dayhoff data bank, we found a homology of six consecutive amino acids between HLA B27.1 antigen residues 72-77 and Klebsiella pneumoniae nitrogenase residues 188-193. These shared sequences are hydrophilic, suggesting locations on molecules exposed to the cell surface. Immunochemical analysis showed that 18 of 34 sera from patients with RS (53%) and 7 of 24 sera from patients with AS (29%) contained antibodies that bound to a synthesized peptide sequence representing residues 69-84 of HLA B27.1. In contrast, only 1 of 22 sera from healthy, B27+ controls (5%) contained antibodies to this peptide (p less than 0.01). Sera from three HLA B27- patients with RS did not possess antibodies to the HLA B27 peptide. Additionally, greater than 40% of HLA B27 patients with AS or RS had antibodies to Klebsiella residues 184-193, while none of the normal nonarthritic HLA B27 haplotype subjects did. Our results suggest that an autoimmune response(s) directed against HLA B27.1 may be a pathogenic mechanism in a subset of patients with AS and RS. Further, this response may initially be induced against Klebsiella pneumoniae, a microorganism that shares sequence homology with HLA B27.
Avoiding the Bad and Enhancing the Good of Soy Supplements in Breast Cancer
Authors: V. C. Jordan
Journal: JNCI Journal of the National Cancer Institute (2014)

Epidemiology teaches us that there is an inverse relationship between soy consumption in Asian countries and a decrease in breast cancer risk. Naturally, this observation sparked a sustained interest in a potential natural approach to the chemoprevention of breast cancer. However, there are many interconnected dimensions to the soy story, some of which are potentially bad. This is the focus of the study by Shike and colleagues (1) in this issue of the Journal.