tbuckley/cabot-search huggingface dataset:
Crohn's disease
Authors: R. Kalla, N. T. Ventham, J. Satsangi, I. D. R. Arnott
Journal: BMJ (2014)

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The T Cell Receptor as a Multicomponent Signalling Machine: CD4/CD8 Coreceptors and CD45 in T Cell Activation
Authors: C A Janeway
Journal: Annual Review of Immunology (1992)

The T cell receptor is a multicomponent signalling machine. The three main components are the hypervariable alpha: beta heterodimer that confers specificity and its attendant invariant chains CD3 gamma, delta, and epsilon and the zeta:zeta or zeta:eta, the CD4 or CD8 coreceptor, and CD45. Each of these components is required for efficient signal transduction, and each has relevant enzymatic activity associated with it. The invariant part of the T cell receptor is associated with the tyrosine kinase p59fyn, the coreceptors are associated with the tyrosine kinase p56lck, and the cytoplasmic domain of CD45 has tyrosine-specific phosphatase activity. Moreover, there is strong evidence that these components interact in the plane of the membrane, and that these interactions are relevant for signal transduction. Finally, changes in the structure of CD45 that occur during differentiation of T cells alter the interactions of these three components of the signal transducing machinery, perhaps accounting for changes in signal transduction that accompany T-cell development in the thymus and the development of immunological memory cells.
The global landscape of sequence diversity
Authors: José Peregrín-Álvarez, John Parkinson
Journal: Genome biology (2007)

Systematic comparisons between genomic sequence datasets have revealed a wide spectrum of sequence specificity from sequences that are highly conserved to those that are specific to individual species. Due to the limited number of fully sequenced eukaryotic genomes, analyses of this spectrum have largely focused on prokaryotes. Combining existing genomic datasets with the partial genomes of 193 eukaryotes derived from collections of expressed sequence tags, we performed a quantitative analysis of the sequence specificity spectrum to provide a global view of the origins and extent of sequence diversity across the three domains of life. Comparisons with prokaryotic datasets reveal a greater genetic diversity within eukaryotes that may be related to differences in modes of genetic inheritance. Mapping this diversity within a phylogenetic framework revealed that the majority of sequences are either highly conserved or specific to the species or taxon from which they derive. Between these two extremes, several evolutionary landmarks consisting of large numbers of sequences conserved within specific taxonomic groups were identified. For example, 8% of sequences derived from metazoan species are specific and conserved within the metazoan lineage. Many of these sequences likely mediate metazoan specific functions, such as cell-cell communication and differentiation. Through the use of partial genome datasets, this study provides a unique perspective of sequence conservation across the three domains of life. The provision of taxon restricted sequences should prove valuable for future computational and biochemical analyses aimed at understanding evolutionary and functional relationships.
Short-Term Treatment With Atorvastatin Reduces Platelet CD40 Ligand and Thrombin Generation in Hypercholesterolemic Patients
Authors: Valerio Sanguigni, Pasquale Pignatelli, Luisa Lenti, Domenico Ferro, Alfonso Bellia, Roberto Carnevale, Manfredi Tesauro, Roberto Sorge, Renato Lauro, Francesco Violi
Journal: Circulation (2005)

Soluble CD40L (sCD40L), a substance that maximally reflects in vivo platelet activation, is increased in patients with hypercholesterolemia. We investigated the relation between sCD40L and platelet CD4OL in hypercholesterolemic patients before and after a short-term treatment with atorvastatin.Collagen-induced platelet CD40L and plasma levels of sCD40L and prothrombin fragment F1+2, a marker of thrombin generation, were investigated in 30 hypercholesterolemic patients and 20 healthy subjects. Hypercholesterolemic patients were then randomized to either diet (n=15; group A) or atorvastatin 10 mg/d (group B); the aforementioned variables were measured at baseline and after 3 days of treatment. Compared with referents, hypercholesterolemic patients showed higher values of platelet CD40L (P<0.005), sCD40L (P<0.005), and F1+2 (P<0.003). Platelet CD40L was significantly correlated with sCD40L (P<0.001), and the latter was significantly correlated with F1+2 (P<0.001). The intervention trial showed no changes in group A but a significant decrease in platelet CD40L (P<0.01), sCD40L (P<0.002), and F1+2 (P<0.03) in group B. In vitro studies demonstrated that cholesterol enhanced platelet CD40L and CD40L-mediated clotting activation by human monocytes; also, atorvastatin dose-dependently inhibited platelet CD40L expression and clotting activation by CD40L-stimulated monocytes.This study shows that, in hypercholesterolemia, platelet overexpression of CD40L may account for enhanced plasma levels of sCD40L and F1+2. Atorvastatin exerts a direct antithrombotic effect via inhibition of platelet CD40L and CD40L-mediated thrombin generation, independently of its cholesterol-lowering effect.
Soluble CD14 acts as a shuttle in the neutralization of lipopolysaccharide (LPS) by LPS-binding protein and reconstituted high density lipoprotein.
Authors: M M Wurfel, E Hailman, S D Wright
Journal: The Journal of Experimental Medicine (1995)

We have recently shown that lipopolysaccharide (LPS)-binding protein (LBP) is a lipid transfer protein that catalyzes two distinct reactions: movement of bacterial LPS (endotoxin) from LPS micelles to soluble CD14 (sCD14) and movement of LPS from micelles to reconstituted high density lipoprotein (R-HDL) particles. Here we show that LBP facilitates a third lipid transfer reaction: movement of LPS from LPS-sCD14 complexes to R-HDL particles. This action of LBP is catalytic, with one molecule of LBP enabling the movement of multiple LPS molecules into R-HDL. LBP-catalyzed movement of LPS from LPS-sCD14 complexes to R-HDL neutralizes the capacity of LPS to stimulate polymorphonuclear leukocytes. Our findings show that LPS may be transferred to R-HDL either by the direct action of LBP or by a two-step reaction in which LPS is first transferred to sCD14 and subsequently to R-HDL. We have observed that the two-step pathway of LPS transfer to R-HDL is strongly favored over direct transfer. Neutralization of LPS by LBP and R-HDL was accelerated more than 30-fold by addition of sCD14. Several observations suggest that sCD14 accelerates this reaction by serving as a shuttle for LPS: addition of LBP and sCD14 to LPS micelles resulted in LPS-sCD14 complexes that could diffuse through a 100-kD cutoff filter; LPS-sCD14 complexes appeared transiently during movement of LPS to R-HDL facilitated by purified LBP; and sCD14 could facilitate transfer of LPS to R-HDL without becoming part of the final LPS-R-HDL complex. Complexes of LPS and sCD14 were formed transiently when LPS was incubated in plasma, suggesting that these complexes may play a role as intermediates in the neutralization of LPS under physiological conditions. These findings detail a new activity for sCD14 and suggest a novel mechanism for lipid transfer by LBP.
One-year follow-up of Coll2-1, Coll2-1NO<sub>2</sub>and myeloperoxydase serum levels in osteoarthritis patients after hip or knee replacement
Authors: M Deberg, J-E Dubuc, A Labasse, C Sanchez, E Quettier, A Bosseloir, J-M Crielaard, Y Henrotin
Journal: Annals of the Rheumatic Diseases (2007)

To determine Coll2-1, Coll2-1NO(2) and myeloperoxydase (MPO) levels in serum of patients with knee or hip osteoarthritis (OA) before the surgery, 3 months and 1 year after knee or hip replacement.Coll2-1, Coll2-1NO(2) and MPO were measured in 103 patients with isolated symptomatic knee or hip OA candidates for joint replacement. Sera were taken the day before surgery, 3 months and 1 year after hip or knee replacement. Coll2-1 and Coll2-1NO(2) immunohistochemistry was performed on biopsies removed from cartilage lesions.Immunostainings revealed the extensive presence of Coll2-1 and Coll2-1NO(2) in the superficial layer of fibrillated cartilage and around some chondrocytes clusters. Three months after joint replacement, Coll2-1 and MPO serum levels were decreased and even reached the reference value for Coll2-1. By contrast, Coll2-1NO(2) levels remained elevated. At 1-year follow-up, Coll2-1 levels remained at the reference value, MPO levels were similar to those measured at 3 months, and Coll2-1NO(2) levels were unchanged and comparable to the pre-surgery values. However, in patients with pre-surgery values above the median (more than 0.42 nM), Coll2-1NO(2) levels significantly and progressively decreased post-operatively, but tended towards an increase in patients with pre-surgery Coll2-1NO(2) values below the median.The normalisation of Coll2-1 levels 3 months after surgery indicates that Coll2-1 is a disease-specific marker that is sensitive to the structural changes occurring in a single joint. Furthermore, the immunohistochemical findings are consistent with the concept that the major source of serum Coll2-1 is the damaged articular cartilage. Finally, serum MPO levels decreased after joint replacement indicating that neutrophil activation occurs in OA joints, even in the late stage of the disease.
The Ratio of Glycosylated Albumin to Glycosylated Hemoglobin Differs Between Type 2 Diabetic Patients With Low Normoalbuminuria and Those With High Normoalbuminuria or Microalbuminuria
Authors: Masahito Katahira, Mizuki Hanakita, Tatsuo Ito, Mari Suzuki
Journal: Diabetes Care (2013)

Glycosylated albumin (GA) stands as an alternative glycemic marker when glycosylated hemoglobin measurements exhibit abnormal values owing to the various complications affecting the life span of erythrocytes (1). However, GA is affected in patients with albumin metabolism disorders such as nephrotic syndrome, liver cirrhosis, and thyroid disorders (2). Moreover, there are several reports on the renal handling of GA in diabetic nephropathy (3–5). The stage of diabetic nephropathy may affect the GA/A1C ratio. In this study, we examined the effect of the urinary albumin-to-creatinine ratio (UACR) on GA/A1C in type 2 diabetic patients with normoalbuminuria or microalbuminuria.

This was a cross-sectional study. A total group of 835 patients with type 2 diabetes was divided into four groups according to their UACR, as follows: the low-normoalbuminuria group consisted of 261 …
Cognitive deterioration associated with an expedition in an extreme desert environment
Authors: P Maruff, P Snyder, M McStephen, A Collie, D Darby
Journal: British Journal of Sports Medicine (2006)

Prolonged exposure to extreme environments may result in cognitive changes that may influence decision making ability and increasing risk of injury or death.To measure the cognitive performance of a healthy man as he completed a 17 day desert expedition.A computer based cognitive test battery, subjective cognitive rating scale, and measures of physical characteristics were used. Objective cognitive performance was compared with the performance of eight age matched men who remained in their own homes.The speed of psychomotor, attentional, and executive functions decreased as the expedition progressed, but the accuracy of performance remained unaffected. Although some impairments were large, they resolved completely once the expedition was completed. Subjective ratings indicated that the subject had insight into his failing cognitive performance during the expedition.Cognitive performance can be measured repeatedly throughout an expedition in an extreme environment. Cognitive impairment may occur.
ACQUIRED IMMUNODEFICIENCY SYNDROME IN THE CHILD OF A HAEMOPHILIAC
Authors: MargaretV. Ragni, Sharon Kiernan, Bernard Cohen, Alan Winkelstein, BasilZ. Zitelli, FranklinA. Bontempo, AndrewH. Urbach, Joseph Stambouli, BruceS. Rabin, J. Carlton Gartner, J.Jeffrey Malatack, JoelA. Spero, JessicaH. Lewis
Journal: The Lancet (1985)
Nine-Month Outcome of Patients Treated by Percutaneous Coronary Interventions for Bifurcation Lesions in the Recent Era
Authors: Philippe Garot, Thierry Lefèvre, Michael Savage, Yves Louvard, William R. Bamlet, James T. Willerson, Marie-Claude Morice, David R. Holmes
Journal: Journal of the American College of Cardiology (2005)
Adenylyl Cyclase Type 6 Deletion Decreases Left Ventricular Function via Impaired Calcium Handling
Authors: Tong Tang, Mei Hua Gao, N. Chin Lai, Amy L. Firth, Toshiyuki Takahashi, Tracy Guo, Jason X.-J. Yuan, David M. Roth, H. Kirk Hammond
Journal: Circulation (2007)

Background— Adenylyl cyclases (ACs) are a family of effector molecules for G-protein–coupled receptors. The 2 ACs most abundantly expressed in cardiac myocytes are types 5 (AC5) and 6 (AC6), which have 65% amino acid homology. It has been speculated that coexpression of 2 AC types in cardiac myocytes represents redundancy, but the specific role of AC6 in cardiac physiology and its differences from AC5 remain to be defined. Methods and Results— We generated transgenic mice with targeted deletion of AC6. Deletion of AC6 was associated with reduced left ventricular contractile function ( P =0.026) and relaxation ( P =0.041). The absence of AC6 was associated with a 48% decay in β-adrenergic receptor–stimulated cAMP production in cardiac myocytes ( P =0.003) and reduced protein kinase A activity ( P =0.015). In addition, phospholamban phosphorylation was reduced ( P =0.015), sarcoplasmic reticulum Ca 2+ -ATPase activity was impaired ( P &lt;0.0001), and cardiac myocytes showed marked abnormalities in calcium transient formation ( P =0.001). Conclusions— The combination of impaired cardiac cAMP generation and calcium handling that result from AC6 deletion underlies abnormalities in left ventricular function. The biochemical and physiological consequences of AC6 deletion reveal it to be an important effector molecule in the adult heart, serving unique biological functions not replicated by AC5.
Acute unclassified leukemia. A clinicopathologic study with diagnostic implications of electron microscopy
Authors: Ehsan Youness, Jose M. Trujillo, Michael J. Ahearn, Kenneth B. McCredie, Ann Cork
Journal: American Journal of Hematology (1980)

Abstract By rigid cytological and cytochemical criteria, the diagnosis of acute and undifferentiated leukemia was established in 22 patients. According to defined criteria, the leukemic cells could not be classified by conventional light microscopic techniques employed in the study of hematopoietic tissue. Cytochemical studies including peroxidase, periodic acid schiff (PAS) and nonspecific esterase (alpha napthyl butyrate‐reacting esterase) stains were done on fresh bone marrow samples, and the percentage of positive leukemia cells for each of these stains was determined on 200 cells. In this series of leukemias, cytochemistry at the light microscope level did not contribute to further classification. Subsequent electron microscopic examination of bone marrow samples from these patients confirmed the immaturity and nuclear/cytoplasmic asynchrony of the leukemic cells. Several in vivo neoplastic markers, such as nuclear blebs, increased nuclear bodies, and cytoplasmic fibrillar bundles could be demonstrated in these cells. Fourteen cases from this series exhibited peroxidase‐positive developmental granule formation at the ultrastructural level and were reclassified as acute granulocytic leukemia (AGL). One case was reclassified as lymphoma (poor differentiated type), one case was diagnosed as acute monocytic leukemia (AMonoL), and six cases remained in the undifferentiated category (AUL). Clinical and laboratory features, response to treatment, and survival data were evaluated for these patients. This study demonstrated that electron microscopy is useful in the cytological diagnosis of human leukemia.
The Need to Test the Patient-Centered Medical Home
Authors: Michael S. Barr
Journal: JAMA (2008)

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Monocytes regulate osteoclast-activating factor production by releasing prostaglandins.
Authors: T Yoneda, G R Mundy
Journal: The Journal of Experimental Medicine (1979)

Osteoclast-activating factor (OAF), a powerful stimulator of osteoclastic bone resorption, is released by peripheral blood mononuclear cells on exposure to phytohemagglutinin (PHA) or a specific antigen to which the leukocytes have been previously exposed. Both lymphocytes and monocytes are required in the leukocyte population for OAF release to occur. In this study we examined the relationship between the lymphocyte and monocyte in OAF production. Biological activity, as a result of OAF, was assessed by a bioassay based on the release of previously incorporated 45Ca from fetal rodent long bones in organ culture. We found that an enriched lymphocyte population depleted of monocytes by serial adherence does not release OAF after stimulation with PHA, although the cells are activated as assessed by [3H]thymidine and 3H-amino acid incorporation. When conditioned media harvested from adherent cells which did not contain OAF was added to the enriched lymphocytes, OAF release occurred. Media harvested from adherent cells which were cultured with indomethacin (10 microM), an inhibitor of prostaglandin synthesis, did not permit OAF release by activated lymphocytes. When PGE1 and PGE2 (0.1 microM) were added exogenously to the enriched lymphocyte population, OAF release occurred after stimulation with PHA. These results indicate that, (a) the activated lymphocyte is the cell or origin of OAF, (b) prostaglandins produced by monocytes are necessary for OAF production by activated lymphocytes, and (c) monocyte prostaglandins can influence bone resorption indirectly by regulating OAF production as well as directly by osteoclast activation. The interactions of OAF and prostaglandins at bone resorbing sites may be important in inflammatory and neoplastic diseases associated with bone destruction.
Predominant activation of MAP kinases and pro-destructive/pro-inflammatory features by TNF in early-passage synovial fibroblasts via TNF receptor-1: failure of p38 inhibition to suppress matrix metalloproteinase-1 in rheumatoid arthritis
Authors: E. Kunisch, M. Gandesiri, R. Fuhrmann, A. Roth, R. Winter, R. W Kinne
Journal: Annals of the Rheumatic Diseases (2007)

<b>Objective:</b> To examine the relative importance of tumour necrosis factor-receptor 1 (TNF-R1) and TNF-R2 and their signalling pathways for pro-inflammatory and pro-destructive features of early-passage synovial fibroblasts (SFB) from rheumatoid arthritis (RA) and osteoarthritis (OA). <b>Methods:</b> Cells were stimulated with tumour necrosis factor (TNF)α or agonistic anti-TNF-R1/TNF-R2 monoclonal antibodies. Phosphorylation of p38, ERK and JNK kinases was assessed by western blot; proliferation by bromodesoxyuridine incorporation; interleukin (IL)6, IL8, prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) and matrix metalloproteinase (MMP)-1 secretion by ELISA; and MMP-3 secretion by western blot. Functional assays were performed with or without inhibition of p38 (SB203580), ERK (U0126) or JNK (SP600125). <b>Results:</b> In RA- and OA-SFB, TNFα-induced phosphorylation of p38, ERK or JNK was exclusively mediated by TNF-R1. Reduction of proliferation and induction of IL6, IL8 and MMP-1 were solely mediated by TNF-R1, whereas PGE<sub>2</sub> and MMP-3 secretion was mediated by both TNF-Rs. In general, inhibition of ERK or JNK did not significantly alter the TNFα influence on these effector molecules. In contrast, inhibition of p38 reversed TNFα effects on proliferation and IL6/PGE<sub>2</sub> secretion (but not on IL8 and MMP-3 secretion). The above effects were comparable in RA- and OA-SFB, except that TNFα-induced MMP-1 secretion was reversed by p38 inhibition only in OA-SFB. <b>Conclusion:</b> In early-passage RA/OA-SFB, activation of MAPK cascades and pro-inflammatory/pro-destructive features by TNFα is predominantly mediated by TNF-R1 and, for proliferation and IL6/PGE<sub>2</sub> secretion, exclusively regulated by p38. Strikingly, RA-SFB are insensitive to p38 inhibition of MMP-1 secretion. This indicates a resistance of RA-SFB to the inhibition of pro-destructive functions and suggests underlying structural/functional alterations of the p38 pathway, which may contribute to the pathogenesis or therapeutic sensitivity of RA, or both.