tbuckley/cabot-search huggingface dataset:
Changes in cartilage metabolism in arthritis are reflected by altered serum and synovial fluid levels of the cartilage proteoglycan aggrecan. Implications for pathogenesis.
Authors: A R Poole, M Ionescu, A Swan, P A Dieppe
Journal: Journal of Clinical Investigation (1994)

The metabolism of the cartilage proteoglycan aggrecan was studied in patients with osteoarthritis (OA, n = 83), rheumatoid arthritis (RA, n = 127), and in controls (n = 117) using monoclonal antibody-based radioimmunoassays for glycosaminoglycans in the serum and synovial fluid (SF) to detect epitope 846 on chondroitin sulfate (probably only on recently synthesized molecules) and a keratan sulfate (KS) epitope AN9PI, present on intact and degraded molecules. Epitope 846 levels were always elevated in SF over serum (mean 38-fold in OA and 8.6-fold in RA) being highest in OA patients with the longest disease duration and greatest loss of cartilage, and lowest in RA joints with high leucocyte counts. Serum levels were more often elevated in RA (56%) than in OA (19%) and probably reflect increased aggrecan synthesis in diseased joints. KS levels were higher in SF than in serum in 69% of patients (up to 2.3-fold); levels were inversely (OA) and directly (RA) related to SF leucocyte counts. Serum KS was reduced in both diseases and in RA was inversely related to both systemic and joint inflammation markers. SF 846 levels were inversely related to SF KS in both diseases. These epitopes may provide a measure of the balance between cartilage synthesis and degradation in these diseases.
Rectal bleeding and colorectal cancer in general practice: diagnostic study
Authors: H. Wauters
Journal: BMJ (2000)

Although most cases of rectal bleeding are due to local conditions, this symptom is a major sign of colorectal cancer. Little research exists on whether to refer a patient with rectal bleeding for further evaluation.1-3 We therefore studied the diagnostic value of rectal bleeding in relation to a subsequent diagnosis of colorectal cancer.

In Belgium, a network of sentinel practices, covering 1% of the population, registers epidemiological data.4 The methods used to estimate the denominator (in patient years) have been published.4

We analysed data on all patients with colorectal cancer diagnosed in 1993–4 to evaluate sensitivity (retrospective study). We chose rectal bleeding as the reason for visiting a general practitioner before colorectal cancer was diagnosed as the main outcome measure.

To obtain a positive predictive value (prospective part of study), we included all patients presenting with rectal bleeding in 1993-4. Our reference standard was colorectal cancer diagnosed …
Confirmation of<i>TNIP1</i>but not<i>RHOB</i>and<i>PSORS1C1</i>as systemic sclerosis risk factors in a large independent replication study
Authors: Lara Bossini-Castillo, Jose Ezequiel Martin, Jasper Broen, Carmen P Simeon, Lorenzo Beretta, Olga Y Gorlova, Madelon C Vonk, Norberto Ortego-Centeno, Gerard Espinosa, Patricia Carreira, Paloma García de la Peña, Natividad Oreiro, José Andrés Román-Ivorra, María Jesús Castillo, Miguel A González-Gay, Luis Sáez-Comet, Ivan Castellví, Annemie J Schuerwegh, Alexandre E Voskuyl, Anna-Maria Hoffmann-Vold, Roger Hesselstrand, Annika Nordin, Claudio Lunardi, Raffaella Scorza, Jacob M van Laar, Paul G Shiels, Ariane Herrick, Jane Worthington, Carmen Fonseca, Christopher Denton, Filemon K Tan, Frank C Arnett, Shervin Assassi, Bobby P Koeleman, Maureen D Mayes, Timothy R D J Radstake, Javier Martin
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Introduction</h3> A recent genome-wide association study in European systemic sclerosis (SSc) patients identified three loci (<i>PSORS1C1</i>, <i>TNIP1</i> and <i>RHOB</i>) as novel genetic risk factors for the disease. The aim of this study was to replicate the previously mentioned findings in a large multicentre independent SSc cohort of Caucasian ancestry. <h3>Methods</h3> 4389 SSc patients and 7611 healthy controls from different European countries and the USA were included in the study. Six single nucleotide polymorphisms (SNP): rs342070, rs13021401 (<i>RHOB</i>), rs2233287, rs4958881, rs3792783 (<i>TNIP1</i>) and rs3130573 (<i>PSORS1C1</i>) were analysed. Overall significance was calculated by pooled analysis of all the cohorts. Haplotype analyses and conditional logistic regression analyses were carried out to explore further the genetic structure of the tested loci. <h3>Results</h3> Pooled analyses of all the analysed SNPs in <i>TNIP1</i> revealed significant association with the whole disease (rs2233287 p<sub>MH</sub>=1.94×10<sup>−4</sup>, OR 1.19; rs4958881 p<sub>MH</sub>=3.26×10<sup>−5</sup>, OR 1.19; rs3792783 p<sub>MH</sub>=2.16×10<sup>−4</sup>, OR 1.19). These associations were maintained in all the subgroups considered. <i>PSORS1C1</i> comparison showed association with the complete set of patients and all the subsets except for the anti-centromere-positive patients. However, the association was dependent on different HLA class II alleles. The variants in the <i>RHOB</i> gene were not associated with SSc or any of its subsets. <h3>Conclusions</h3> These data confirmed the influence of <i>TNIP1</i> on an increased susceptibility to SSc and reinforced this locus as a common autoimmunity risk factor.
Cutaneous lymphocytic vasculitis in acute myeloid leukaemia
Authors: A.M. FARRELL, C. GOOPTU, D. WOODROW, C. COSTELLO, C.B. BUNKER, J.J. CREAM
Journal: British Journal of Dermatology (1996)

We report a 63-year-old woman who presented with an 8-week history of widespread indurated, purpuric lesions associated with weight loss of 7 kg and several episodes of epistaxis. A skin biopsy demonstrated a lymphocytic vasculitis with haemorrhage and parakeratosis. A blood flim and bone marrow examination showed features of a myelodysplastic syndrome in transformation to acute myeloid leukaemia. Leucocytoclastic vasculitis and polyarteritis nodosa occur in association with acute myeloid leukaemia, but the association with lymphocytic vasculitis is new.
Resistance to cutaneous graft-vs.-host disease is not induced in T cell receptor delta gene-mutant mice.
Authors: T Shiohara, N Moriya, J Hayakawa, S Itohara, H Ishikawa
Journal: The Journal of Experimental Medicine (1996)

The function of murine dendritic epidermal cells (dEC) remains largely speculative, probably because of the lack of a suitable in vivo model, although previous studies suggest that gamma/delta+ dEC may have originally evolved to serve as a self-protection mechanism(s). Our previous study demonstrated that the epidermis of mice that had spontaneously recovered from cutaneous graft-vs-host disease (GVHD) induced by local injection of CD4+ autoreactive T cells contained unexpectedly large numbers of dEC and became resistant to subsequent attempts to induce GVHD in a site-restricted manner, suggesting that the resistance is mediated by dEC. However, because alpha/beta+ dEC as well as gamma/delta+ dEC were greatly increased in number in the epidermis, it was unclear whether gamma/delta+ dEC are indeed responsible for this protection. The availability of this murine model and mice selectively lacking gamma/delta T cells as a result of disruption of the T cell receptor C delta gene segment allowed us to investigate the role of gamma/delta+ dEC. In the epidermis of gamma/delta T cell-deficient mice (delta-/-), a congenital lack of gamma/delta+ dEC was substituted for by alpha/beta+ dEC of either a CD4-8+ or a CD4-8- phenotype. After intradermal injection of the autoreactive T cells, delta-/- mice developed significantly enhanced delayed-type hypersensitivity responses and cutaneous GVHD, which persisted longer than in heterozygous littermate controls (delta+/-). Surprisingly, resistance to the cutaneous GVHD was not induced in the epidermis of delta-/- mice after spontaneous recovery from the GVHD, whereas the "susceptible" epidermis of delta-/+ mice contained large numbers of alpha/beta dEC comparable to those in "resistant" epidermis of delta+/- mice. Injection of day 16 fetal thymocytes from wild-type mice into delta-/- mice resulted in the appearance of donor-type gamma/delta+ dEC in the epidermis, and reconstitution with gamma/delta+ dEC restored the protective immune response of the epidermis against the GVHD to nearly normal levels. These results indicate that gamma/delta+ dEC are responsible for the site-restricted protection against cutaneous GVHD.
Sex Differences in the Prognosis of Congestive Heart Failure
Authors: Tabassome Simon, Murielle Mary-Krause, Christian Funck-Brentano, Patrice Jaillon
Journal: Circulation (2001)

Background —Whether female sex is associated with a better prognosis in patients with congestive heart failure (CHF) remains uncertain. The Cardiac Insufficiency Bisoprolol Study (CIBIS) II showed that bisoprolol reduced all-cause mortality and morbidity rates in CHF patients treated with diuretics and ACE inhibitors. We examined whether survival was different in men (n=2132) and women (n=515) enrolled in CIBIS II. Methods and Results —Women differed from men with regard to age, NYHA functional classification, primary cause of CHF, and risk factors such as left bundle-branch block. After adjustment for baseline differences, the probability of all-cause mortality was significantly reduced by 36% in women compared with that in men (hazard ratio 0.64, 95% CI 0.47 to 0.86, P =0.003). Women also had a 39% reduction in cardiovascular deaths (hazard ratio 0.64, 95% CI 0.45 to 0.91, P =0.01) and a 70% reduction in deaths from pump failure (hazard ratio 0.30, 95% CI 0.13 to 0.70, P =0.005) compared with men. Kaplan-Meier survival analysis revealed a significant reduction in all-cause mortality among women treated with bisoprolol compared with men (6% versus 12% P =0.01) but not among women treated with placebo (13% versus 18%, P =0.10). However, this sex/β-blocker effect was not significant in multivariate analysis. Conclusions —These results indicate that regardless of β-blocker treatment and baseline clinical profile, female sex is a significant independent predictor of survival in patients with CHF.
Histochemical Studies in Atherogenesis
Authors: FREDERICK T. ZUGIBE, KENNETH D. BROWN
Journal: Circulation Research (1961)

Histochemieal studies of grossly normal and early lesions of cerebral arteries of 75 iudividuals ranging from fetuses to 70 years of age were made, utilizing newer histochemieal techniques. The following conclusions were made: There is no apparent relationship between acid mucopolysaccharides and lipids in respect to staining intensity and/or distribution in any of the age groups. In older juveniles and adults, lipid material was consistently observed intimately associated with the internal elastic membrane and other reduplicated elastic fibers, even in the absence of gross lesions. Fragmentation, fraying, and/or reduplication of the internal elastic membrane were absent in the fetuses, infants, and young juveniles. There was no apparent association between lipid and these elastic changes. In fetuses, infants, and young juveniles there was an accumulation of acid mucopolysaccharides hydrolyzable by testicular hyaluronidase, principally in the area of the proximal media, suggesting that the polysaccharide material was hyaluronic acid and/or chondroitin sulfate A and/or chondroitin sulfate C. In the adults, there was an accumulation in acid mucopolysaccharides resistant to hydrolysis by testicular hyaluronidase in the proximal media and in the intima. This accumulation in acid mucopolysaccharides corresponded to the areas of collagen increase. It was further suggested that these polysaccharides were chondroitin sulfate B and/or heparitin sulfate and/or hepa-rin. The significance of these findings was discussed.
Long-term effect of Helicobacter pylori eradication on plasma homocysteine in elderly patients with cobalamin deficiency
Authors: M. C. A. Marino, C. A. de Oliveira, A. M. C. Rocha, G. A. Rocha, N. C. D. Clementino, L. F. Antunes, R. A. Oliveira, A. S. Martins, H. L. Del Puerto, V. D'Almeida, L. Galdieri, E. R. P. Pedroso, M. M. D. A. Cabral, A. M. M. F. Nogueira, D. M. M. Queiroz
Journal: Gut (2006)

<b>Background:</b><i>Helicobacter pylori</i> gastritis may lead to impairment of the production of pepsinogen and acid, which are essential to cobalamin absorption. In turn, cobalamin deficiency leads to hyperhomocysteinaemia, a risk factor for cardio and cerebrovascular diseases. <b>Aim:</b> To evaluate the effect of <i>H pylori</i> eradication on plasma homocysteine levels in elderly patients. <b>Patients:</b> Sixty-two <i>H pylori</i>-positive elderly patients with cobalamin deficiency were prospectively studied. <b>Methods:</b> Homocysteine and cobalamin concentrations were determined before, 6 and 12 months after <i>H pylori</i> eradication. <b>Results:</b> Corpus atrophy was observed in a few patients; otherwise, in most of them, the degree of corpus gastritis was moderate to severe. The initial homocysteine mean (SD) levels decreased from 41.0 (27.1) to 21.6 (10.1) μmol/l at the 6 month follow-up (p&lt;0.001) and to 13.1 (3.8) μmol/l 12 months after <i>H pylori</i> eradication (p&lt;0.001). Conversely, initial cobalamin mean levels increased from 145.5 (48.7) pmol/l to 209.8 (87.1) pmol/l and to 271.2 (140.8) pmol/l, 6 and 12 months after treatment, respectively (p&lt;0.001 for both). Although the erythrocyte mean corpuscular volume was within reference intervals, it decreased significantly 6 (p = 0.002) and 12 (p&lt;0.001) months after treatment. <b>Conclusions:</b> The results of the current study demonstrated that the eradication of <i>H pylori</i> in elderly patients with cobalamin deficiency is followed by increasing of cobalamin and decreasing of homocysteine blood levels.
Annual risk of infection with Mycobacterium tuberculosis
Authors: H. Rieder
Journal: European Respiratory Journal (2005)

The average annual risk of infection with Mycobacterium tuberculosis is a calculated average from an observed prevalence of infection, approximating the incidence of infection. It has the potential to be informative about the extent of transmission in a community. Where serial surveys are available, secular trends in transmission might be ascertained. The prerequisite for calculating the average annual risk is the successful determination of the prevalence of infection. Difficulties arising with tuberculin skin-test surveys include logistical problems in sampling a representative portion of the population. Therefore, a compromise assesses the prevalence of infection among school children as an indicator of transmission in the community at large. The utilisation of tuberculin surveys is further compounded by the unpredictable specificity of the tuberculin skin test and, thus, the predictive value of a positive test result. Statistical approaches using mixture analysis may overcome this problem to some extent, but the experience is limited. Cytokine-derived assays, such as the interferon-γ release assays, are promising in providing higher specificity, but they require venepuncture.
Cobalamin absorption and hematologic status after two types of gastric surgery for obesity
Authors: Charles E. Yale, Paul N. Gohdes, Robert F. Schilling
Journal: American Journal of Hematology (1993)

Abstract A series of morbidly obese patients was treated surgically with a gastric bypass, and a subsequent series received a vertical banded gastroplasty. To compare some of the nutritional effects of these two procedures we measured serum vitamin B 12 levels, absorption of food vitamin B 12 , frequency of microcytosis of erythrocytes, and frequency of anemia at one or more years after surgery. Patients with a gastric bypass showed greater weight loss, a greater frequency of microcytosis and anemia, more frequent subnormal serum levels of vitamin B 12 , and impressive failure to absorb food vitamin B 12 . Boiling the food containing vitamin B 12 led to increased absorption. © 1993 Wiley‐Liss, Inc.
Regulation of Endothelial Cell Differentiation and Specification
Authors: Kathrina L. Marcelo, Lauren C. Goldie, Karen K. Hirschi
Journal: Circulation Research (2013)

The circulatory system is the first organ system to develop in the vertebrate embryo and is critical throughout gestation for the delivery of oxygen and nutrients to, as well as removal of metabolic waste products from, growing tissues. Endothelial cells, which constitute the luminal layer of all blood and lymphatic vessels, emerge de novo from the mesoderm in a process known as vasculogenesis. The vascular plexus that is initially formed is then remodeled and refined via proliferation, migration, and sprouting of endothelial cells to form new vessels from preexisting ones during angiogenesis. Mural cells are also recruited by endothelial cells to form the surrounding vessel wall. During this vascular remodeling process, primordial endothelial cells are specialized to acquire arterial, venous, and blood-forming hemogenic phenotypes and functions. A subset of venous endothelium is also specialized to become lymphatic endothelium later in development. The specialization of all endothelial cell subtypes requires extrinsic signals and intrinsic regulatory events, which will be discussed in this review.
Structure, Function, and Inhibition of Chemokines
Authors: Elias J. Fernandez, Elias Lolis
Journal: The Annual Review of Pharmacology and Toxicology (2002)

Chemokines are the largest family of cytokines in human immunophysiology. These proteins are defined by four invariant cysteines and are categorized based on the sequence around the first two cysteines, which leads to two major and two minor subfamilies. Chemokines function by activating specific G protein–coupled receptors, which results in, among other functions, the migration of inflammatory and noninflammatory cells to the appropriate tissues or compartments within tissues. Some of these proteins and receptors have been implicated or shown to be involved in inflammation, autoimmune diseases, and infection by HIV-1. The three-dimensional structure of each monomer is virtually identical, but the quaternary structure of chemokines is different for each subfamily. Structure-function studies reveal several regions of chemokines to be involved in function, with the N-terminal region playing a dominant role. A number of proteins and small-molecule antagonists have been identified that inhibit chemokine activities. In this review, we discuss aspects of the structure, function, and inhibition of chemokines.
Intravenous Immune Globulin Acts in an Fc-Gamma-Receptor-Independent Manner in an Antigen-Driven Murine Model of Allergic Asthma
Authors: Gabriel N. Kaufman, Amir Hossein Massoud, Ryan Fiter, Ciriaco Piccirillo, Bruce D. Mazer
Journal: Journal of Allergy and Clinical Immunology (2013)
c-Rel is required for the development of thymic Foxp3+ CD4 regulatory T cells
Authors: Iwao Isomura, Stephanie Palmer, Raelene J. Grumont, Karen Bunting, Gerard Hoyne, Nancy Wilkinson, Ashish Banerjee, Anna Proietto, Raffi Gugasyan, Li Wu, Alice McNally, Raymond J. Steptoe, Ranjeny Thomas, M. Frances Shannon, Steve Gerondakis
Journal: The Journal of Experimental Medicine (2009)

During thymopoiesis, a unique program of gene expression promotes the development of CD4 regulatory T (T reg) cells. Although Foxp3 maintains a pattern of gene expression necessary for T reg cell function, other transcription factors are emerging as important determinants of T reg cell development. We show that the NF-κB transcription factor c-Rel is highly expressed in thymic T reg cells and that in c-rel−/− mice, thymic T reg cell numbers are markedly reduced as a result of a T cell–intrinsic defect that is manifest during thymocyte development. Although c-Rel is not essential for TGF-β conversion of peripheral CD4+CD25− T cells into CD4+Foxp3+ cells, it is required for optimal homeostatic expansion of peripheral T reg cells. Despite a lower number of peripheral T reg cells in c-rel−/− mice, the residual peripheral c-rel−/− T reg cells express normal levels of Foxp3, display a pattern of cell surface markers and gene expression similar to those of wild-type T reg cells, and effectively suppress effector T cell function in culture and in vivo. Collectively, our results indicate that c-Rel is important for both the thymic development and peripheral homeostatic proliferation of T reg cells.
Preoperative treatment of postmenopausal breast cancer patients with letrozole: A randomized double-blind multicenter study
Authors: W. Eiermann, S. Paepke, J. Appfelstaedt, A. Llombart-Cussac, J. Eremin, J. Vinholes, L. Mauriac, M. Ellis, M. Lassus, H.A. Chaudri-Ross, M. Dugan, M. Borgs, V. Semiglazov
Journal: Annals of Oncology (2001)
Arterial Stiffness in Mild-to-Moderate CKD
Authors: Ashish Upadhyay, Shih-Jen Hwang, Gary F. Mitchell, Ramachandran S. Vasan, Joseph A. Vita, Plamen I. Stantchev, James B. Meigs, Martin G. Larson, Daniel Levy, Emelia J. Benjamin, Caroline S. Fox
Journal: Journal of the American Society of Nephrology (2009)

Whether arterial stiffness correlates with mild-to-moderate CKD and albuminuria in the community is unclear. We studied the association between arterial stiffness and mild-to-moderate CKD and albuminuria in the Framingham Heart Study. CKD was present in 6.7% (181 of 2682) of participants and microalbuminuria was present in 8.2% (479 of 5818). The measures of arterial stiffness were the carotid femoral pulse wave velocity, forward pressure wave amplitude, central pulse pressure, augmentation pressure, augmentation index, and mean arterial pressure. In cross-sectional analyses, arterial stiffness did not associate with CKD (defined by estimated GFR <60 ml/min/1.73 m(2)) in either age- and gender-adjusted or multivariable-adjusted linear regression models. Carotid femoral pulse wave velocity associated with both urinary albumin-to-creatinine ratio and microalbuminuria (P < 0.0001 after multivariable adjustment). In longitudinal analyses, we used logistic regression models to examine the associations between baseline arterial stiffness measures (exposure variables) and incident CKD or microalbuminuria (n = 1675 for CKD analyses and n = 1252 for microalbuminuria analyses). Baseline arterial measures did not associate with incident CKD or incident microalbuminuria. In summary, arterial stiffness correlates with albuminuria but not with mild-to-moderate CKD.