tbuckley/cabot-search huggingface dataset:
Patterns of Myocardial Endothelin-1 Expression and Outcome After Cardiac Transplantation
Authors: Claudio Ferri, Giuliana Properzi, Gianluca Tomassoni, Anna Santucci, Giovambattista Desideri, Anna Elisa Giuliani, Randall C. Starling, Norman B. Ratliff, Daniel J. Cook, Patrick McCarthy, James B. Young, Mohamad H. Yamani
Journal: Circulation (2002)

Endothelin-1 (ET-1), a potent vasoconstrictor, is released in response to several inflammatory cytokines after heart transplantation. The present study correlated patterns of myocardial ET-1 expression in heart biopsies with acute rejection, post-transplantation ischemic injury, and subsequent development of coronary vasculopathy.Patterns of myocardial ET-1 expression were evaluated in 47 heart transplant recipients at 3 months after transplant. Transplant vasculopathy was documented by coronary angiography at 2 years after transplant. Expression of ET-1 was tabulated for both blood vessels and the interstitium. Vascular ET-1 expression was positive in 7/17 (41%) of patients with greater than grade 2 (International Society Heart Lung Transplant) rejection compared with 3/30 (10%) of patients with grade 0 and grade 1A rejection (P=0.02). Compared with patients with negative interstitial ET-1 expression (n=22), patients with positive interstitial ET-1 expression (n=25) had higher incidence of post-transplantation ischemic injury (52% versus 9%, P=0.002), lower mean episodes of acute rejection (> or = grade 2) during the first 3 months of transplant (1.09+/-0.66 versus 1.86+/-1.6, P=0.048), and more common vasculopathy at 2 years (50% versus 15%, P=0.02), and they tended to have worse survival (83.2% versus 100%, P=0.058).Vascular ET-1 expression is likely to be associated with acute rejection. Interstitial ET-1 expression, however, is more likely to be associated with post-transplantation ischemic injury and subsequent development of coronary vasculopathy.
Rhinovirus Enhances Eosinophil Activation through the Production of IL-5 in Acute Exacerbation of Childhood Asthma
Authors: M. Kato, H. Tsukagoshi, M. Yoshizumi, M. Saitoh, K. Kozawa, Y. Yamada, K. Maruyama, Y. Hayashi, H. Kimura
Journal: Journal of Allergy and Clinical Immunology (2009)
The A5.1 allele of the major histocompatibility complex class I chain-related gene A is associated with psoriasis vulgaris in Chinese
Authors: L. Cheng, S.Z. Zhang, C.Y. Xiao, Y.P. Hou, L. Li, H.C. Luo, H.Y. Jiang, W.Q. Zuo
Journal: British Journal of Dermatology (2000)

Recent studies have demonstrated an association of a polymorphic (GCT)n triplet repeat in the transmembrane (TM) region of the major histocompatibility complex (MHC) class I chain-related gene A (MICA), one of the MHC class I chain-related (MIC) family members, with some autoimmune diseases, including Behçet's disease, acute anterior uveitis, Takayasu's arteritis and others.The aim of this study was to examine whether the MICA gene is associated with psoriasis vulgaris (PS) in Chinese.The (GCT)n polymorphism of the MICA gene was investigated in 200 healthy Chinese of Han origin and 300 patients with PS by polymerase chain reaction amplification and denaturing polyacrylamide gel electrophoresis.Five alleles, namely A4, A5, A6, A9 and A5.1 were found in both groups. Comparison of the data from both groups revealed that the A5.1 allele was present at a significantly higher frequency in the patient group (41.5%) than in the control group (23.0%) (Pc < 0.0001, Pc means the probability of a comparison with the control group). The frequency of A5.1-positive cases was also significantly increased in the patient group (68.0%) as compared with the controls (38.0%) (Pc < 0.0001). Furthermore, the carrier frequency of A5.1-positive was significantly increased in psoriatic patients with a positive family history and with early onset as compared with sporadic cases (Pc = 0.0005) and with late onset PS (Pc = 0.002).These results suggest that the MICA gene may be associated with the development of PS in Chinese.
Degradation of porcine dermal connective tissue by collagenase and hyaluronidase
Authors: K. FRIEDMAN, S.V. POLLACK, T. MANNING, S.R. PINNELL
Journal: British Journal of Dermatology (1986)

Selective destruction of connective tissue may be a useful therapeutic tool in conditions associated with abnormal deposition of scar tissue. We have investigated intradermal injections of clostridial collagenase and bovine testicular hyaluronidase alone and in combination in Yucatan miniature hairless pigs. Collagenase in combination with hyaluronidase was quite efficient at destroying the connective tissue matrix, although elastic tissue appeared to be completely spared. Collagenase alone at higher doses degraded collagen, but hyaluronidase had little effect on connective tissue architecture.
Effect of Aging on A1C Levels in Individuals Without Diabetes
Authors: Lydie N. Pani, Leslie Korenda, James B. Meigs, Cynthia Driver, Shadi Chamany, Caroline S. Fox, Lisa Sullivan, Ralph B. D’Agostino, David M. Nathan
Journal: Diabetes Care (2008)

OBJECTIVE—Although glycemic levels are known to rise with normal aging, the nondiabetic A1C range is not age specific. We examined whether A1C was associated with age in nondiabetic subjects and in subjects with normal glucose tolerance (NGT) in two population-based cohorts. RESEARCH DESIGN AND METHODS—We performed cross-sectional analyses of A1C across age categories in 2,473 nondiabetic participants of the Framingham Offspring Study (FOS) and in 3,270 nondiabetic participants from the National Health and Nutrition Examination Survey (NHANES) 2001–2004. In FOS, we examined A1C by age in a subset with NGT, i.e., after excluding those with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT). Multivariate analyses were performed, adjusting for sex, BMI, fasting glucose, and 2-h postload glucose values. RESULTS—In the FOS and NHANES cohorts, A1C levels were positively associated with age in nondiabetic subjects. Linear regression revealed 0.014- and 0.010-unit increases in A1C per year in the nondiabetic FOS and NHANES populations, respectively. The 97.5th percentiles for A1C were 6.0% and 5.6% for nondiabetic individuals aged &amp;lt;40 years in FOS and NHANES, respectively, compared with 6.6% and 6.2% for individuals aged ≥70 years (Ptrend &amp;lt; 0.001). The association of A1C with age was similar when restricted to the subset of FOS subjects with NGT and after adjustments for sex, BMI, fasting glucose, and 2-h postload glucose values. CONCLUSIONS—A1C levels are positively associated with age in nondiabetic populations even after exclusion of subjects with IFG and/or IGT. Further studies are needed to determine whether age-specific diagnostic and treatment criteria would be appropriate.
The Effects of Cyanate In Vitro on Red Blood Cell Metabolism and Function in Sickle Cell Anemia
Authors: Frank G. De Furia, Denis R. Miller, Anthony Cerami, James M. Manning
Journal: Journal of Clinical Investigation (1972)

Cyanate, which is in equilibrium with urea, combines with the alpha-amino group of the aminoterminal valine of hemoglobin in an irreversible, specific carbamylation reaction. Partial carbamylation (0.72 residues/hemoglobin tetramer) as determined by cyanate-(14)C incorporation or hydantoin analysis diminishes the in vitro sickling phenomenon. Since cyanate may react not only with hemoglobin but also with functional groups of other red blood cell proteins, the in vitro effect of cyanate was studied on sickle cells. Cells were incubated with 10 mM KCl (control) or 10 mM KNCO (carbamylated) for 1 hr, washed, and resuspended in autologous plasma. Glycolysis, ATP and 2,3-diphosphoglyceric acid (DPG) stability, autohemolysis, and osmotic fragility were not affected by carbamylation. Potassium loss in carbamylated cells (2.8 mmol/liter) was less than in control cells (9.0 mmol/liter). Pyruvate kinase activity of carbamylated cells was decreased ( approximately 25%) but the activities of other glycolytic enzymes were similar to those of control cells. Oxygen affinity of carbamylated sickle, normal, and DPG-depleted normal cells increased, and was a sensitive index of the degree and duration of reaction with cyanate. The reactivity of carbamylated cells to DPG was similar to control cells. DPG-depleted carbamylated cells regenerated DPG and increased the P(50) when incubated with pyruvate, inosine, and phosphate. The Bohr effect of normal and of sickle cells was not affected (Deltalog P(50)/Delta pH=-0.48 and -0.53, respectively) after carbamylation. The reserve buffering capacity of plasma offset the slightly diminished ( approximately 15%) CO(2) capacity of carbamylated cells so that whole blood CO(2) capacity, pH, and P(CO2) were normal. These studies provide further support for the potential clinical use of cyanate in treating and preventing the anemia and painful crises of sickle cell disease.
SURGICAL MANAGEMENT OF ATRIOVENTRICULAR SEPTAL DEFECTS WITH AORTIC ARCH OBSTRUCTION IN NEONATES: A MULTICENTER STUDY
Authors: John M. Costello, Jeffrey Shuhaiber, Andrew Shin, Jeffrey Gossett, David Wypij, Carl Backer, Frank Hanley, Muhammad S. Khan, Charles Fraser, Frederic Jacques, Glen Van Arsdell, John Mayer
Journal: Journal of the American College of Cardiology (2012)
Adherence of rheumatoid polymorphonuclear cells (PMNs) to cultured endothelial cell monolayers.
Authors: N J Sheehan, K A Brown, J D Perry, R C Chasty, D A Yates, D C Dumonde
Journal: Annals of the Rheumatic Diseases (1987)

<h3>Abstract</h3> Primate herpes simplex viruses are relatively harmless to their natural hosts, whereas cross-species transmission can result in severe disease. We performed a genome-wide scan for signals of adaptation of simplexviruses to hominins. We found evidence of positive selection in three glycoproteins, with selected sites located in antigenic determinants. Positively selected non-core proteins were involved in different immune-escape mechanisms. By expressing mutants of one of these proteins (ICP47), we show that the amino acid status at the positively selected sites is sufficient to induce HLA-G. HSV-1/HSV-2 ICP47 induced HLA-G when mutated to recapitulate residues in B virus, whereas the mutated version of B virus ICP47 failed to determine HLA-G expression. Thus, the evolution of ICP47 in HSV-1/HSV-2 determined the loss of an immunosuppressive effect, suggesting that simplexviruses tune immune responses to promote successful co-existence with their hosts. These results also help explain the high pathogenicity of B virus in humans.
Relaxed Clocks and Inferences of Heterogeneous Patterns of Nucleotide Substitution and Divergence Time Estimates across Whales and Dolphins (Mammalia: Cetacea)
Authors: A. Dornburg, M. C. Brandley, M. R. McGowen, T. J. Near
Journal: Molecular Biology and Evolution (2011)

Various nucleotide substitution models have been developed to accommodate among lineage rate heterogeneity, thereby relaxing the assumptions of the strict molecular clock. Recently developed "uncorrelated relaxed clock" and "random local clock" (RLC) models allow decoupling of nucleotide substitution rates between descendant lineages and are thus predicted to perform better in the presence of lineage-specific rate heterogeneity. However, it is uncertain how these models perform in the presence of punctuated shifts in substitution rate, especially between closely related clades. Using cetaceans (whales and dolphins) as a case study, we test the performance of these two substitution models in estimating both molecular rates and divergence times in the presence of substantial lineage-specific rate heterogeneity. Our RLC analyses of whole mitochondrial genome alignments find evidence for up to ten clade-specific nucleotide substitution rate shifts in cetaceans. We provide evidence that in the uncorrelated relaxed clock framework, a punctuated shift in the rate of molecular evolution within a subclade results in posterior rate estimates that are either misled or intermediate between the disparate rate classes present in baleen and toothed whales. Using simulations, we demonstrate abrupt changes in rate isolated to one or a few lineages in the phylogeny can mislead rate and age estimation, even when the node of interest is calibrated. We further demonstrate how increasing prior age uncertainty can bias rate and age estimates, even while the 95% highest posterior density around age estimates decreases; in other words, increased precision for an inaccurate estimate. We interpret the use of external calibrations in divergence time studies in light of these results, suggesting that rate shifts at deep time scales may mislead inferences of absolute molecular rates and ages.
T2 Magnetic Resonance Enables Nanoparticle-Mediated Rapid Detection of Candidemia in Whole Blood
Authors: Lori A. Neely, Mark Audeh, Nu Ai Phung, Michael Min, Adam Suchocki, Daniella Plourde, Matthew Blanco, Vasiliki Demas, Lynell R. Skewis, Theodora Anagnostou, Jeffrey J. Coleman, Parris Wellman, Eleftherios Mylonakis, Thomas J. Lowery
Journal: Science Translational Medicine (2013)

Nanoparticles and T2 magnetic resonance allow for DNA amplification and detection of Candida species in clinical whole-blood specimens.
The role of <i>LTA4H</i> and <i>ALOX5AP</i> polymorphism in asthma and allergy susceptibility
Authors: J. W. Holloway, S. J. Barton, S. T. Holgate, M. J. Rose‐Zerilli, I. Sayers
Journal: Allergy (2008)

Leukotrienes (LTs) have been identified as central mediators in asthma and allergy. Pharmacological inhibition of cysteinyl-LT activity improves asthma symptoms and control. Accumulating evidence suggests a role for the dihydroxy leukotriene LTB(4) in airway disease. LTA(4) hydrolase and 5-lipoxygenase activating protein have key roles in LTB(4) production. Single nucleotide polymorphism (SNPs) and haplotypes spanning the LTA4H and ALOX5AP genes have been associated with LTB(4) production and myocardial infarction (MI).To assess the contribution of LTA4H and ALOX5AP polymorphism to asthma and allergy susceptibility.Three hundred and forty-one Caucasian families (two asthmatic siblings) were genotyped for eight SNPs spanning ALOX5AP and five SNPs spanning LTA4H. Association analyses of asthma and related phenotypes (total IgE, atopy, bronchial hyper-responsiveness, FEV(1)) were undertaken using the Family Based Association Test.Single point analyses identified association (P < 0.05) between SNPs SG13S114, SG13S89, SG13S41 (ALOX5AP), rs1978331 (LTA4H) and asthma and/or related phenotypes. Haplotype analyses using all LTA4H SNPs identified a single key risk haplotype for the development of asthma (P = 0.006) and related phenotypes (P = 0.042-0.005). Haplotype analyses using all ALOX5AP SNPs identified several asthma and atopy risk and protective haplotypes. There was limited correlation with previously identified MI risk haplotypes in both genes. Carriers of both ALOX5AP SG13S41 and LTA4H rs1978331 alleles had an increased risk of developing asthma (OR 2.17, CI 1.41-3.32).These data provide evidence for the role of SNPs spanning the ALOX5AP and LTA4H genes in asthma and atopy susceptibility in the Caucasian population and support a role for LTB(4) in disease pathogenesis.
Granulomatous destruction of bile ducts after liver transplantation: Primary biliary cirrhosis recurrence or hepatitis C virus infection?
Authors: Olivier Farges, Henri Bismuth, Mylène Sebagh, Michel Reynes, Vijayan Balan, Michael K. Porayko, Ruud A. F. Krom, Russell H. Wiesner, Kenneth P. Batts, Jurgen Ludwig
Journal: Hepatology (1995)
Prolonged exposure to acetaminophen reduces testosterone production by the human fetal testis in a xenograft model
Authors: Sander van den Driesche, Joni Macdonald, Richard A. Anderson, Zoe C. Johnston, Tarini Chetty, Lee B. Smith, Chris McKinnell, Afshan Dean, Natalie Z. Homer, Anne Jorgensen, Maria E. Camacho-Moll, Richard M. Sharpe, Rod T. Mitchell
Journal: Science Translational Medicine (2015)

Prolonged exposure to therapeutic doses of acetaminophen reduces testosterone production by human fetal testis xenografts in mice.
CHEMOPATHOLOGICAL STUDIES WITH COMPOUNDS OF ARSENIC
Authors: Louise Pearce, Wade H. Brown
Journal: The Journal of Experimental Medicine (1916)

1. The processes of repair in the kidneys of guinea pigs after sublethal doses of certain arsenical compounds indicate that all arsenicals do not produce a purely vascular type of renal injury. 2. While some arsenicals produce a predominantly vascular injury and others produce a predominantly tubular injury, both these tissue elements are undoubtedly always affected, although in varying proportion. In addition, the interstitial connective tissue is probably always affected. The diffuse proliferation of this tissue may be relatively conspicuous in the processes of repair after arsenicals that cause but slight vascular injury. 3. All red kidneys do not necessarily show identical pictures during the processes of repair; the same is true of pale kidneys. 4. The mode of action of an arsenical compound as a renal toxic agent is bound up with the chemical constitution of the compound.
Hormonal manipulation of the immune response in systemic lupus erythematosus: a drug trial of an anabolic steroid, 19-nortestosterone.
Authors: R A Hazelton, A B McCruden, R D Sturrock, W H Stimson
Journal: Annals of the Rheumatic Diseases (1983)

Ten patients (8 female, 2 male) with systemic lupus erythematosus (SLE) were entered into an open trial with the anabolic steroid 19-nortestosterone (19-nor). Their clinical condition did not improve, nor were significant changes observed in the majority of laboratory data. However, overall the platelet count rose, and in patients with abnormal levels of T lymphocytes bearing receptors for IgG Fc treatment returned the values to normal. Despite this latter result, suppressor cell activity remained slightly below the normal range throughout the study period.
Relationship Between Allergen-Induced Basophil Histamine Release and CD203c Stimulation During Omalizumab Treatment
Authors: P.M. Sterba, V. Alexander, J.A. Eckman, D.C. Kelly, D.M. MacGlashan, B.S. Bochner, S.S. Saini
Journal: Journal of Allergy and Clinical Immunology (2009)
YIELD OF UNPREDICTED BONE-MARROW RELAPSE DIAGNOSED BY ROUTINE MARROW ASPIRATION IN CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKAEMIA
Authors: PaulC.J. Rogers, Peter Coccia, Stuart Siegel, W.Archie Bleyer, JohnN. Lukens, Harland Sather, Denman Hammond
Journal: The Lancet (1984)
The importance of genetic influences in asthma
Authors: H Los, GH Koppelman, DS Postma
Journal: European Respiratory Journal (1999)

Asthma is a complex genetic disorder in which the mode of inheritance is not known. Many segregation studies suggest that a major gene could be involved in asthma, but until now different genetic models have been obtained. Twin studies, too, have shown evidence for genetic influences in asthma, but have also revealed substantial evidence for environmental influences, in which nonshared environmental influences appeared to be important. Linkage, association studies and genome-wide screening suggest that multiple genes are involved in the pathogenesis of asthma. At least four regions of the human genome, chromosomes 5q31-33, 6p21.3, 11q13 and 12q14.3-24.1, contain genes consistently found to be associated with asthma and associated phenotypes. Not only genes associated with asthma but also genes which are involved in the development and outcome of asthma will be found in the future. This will probably provide greater insight into the identification of individuals at risk of asthma and early prevention and greater understanding for guiding therapeutic intervention in asthma. Exchange of information between researchers involved in the genetics of asthma is important because of mandatory agreement on phenotypes and analytical approaches. Genetics will contribute to the a better understanding and management of asthma in the future.
Pathologic Response to Preoperative Chemotherapy: A New Outcome End Point After Resection of Hepatic Colorectal Metastases
Authors: Dan G. Blazer, Yoji Kishi, Dipen M. Maru, Scott Kopetz, Yun Shin Chun, Michael J. Overman, David Fogelman, Cathy Eng, David Z. Chang, Huamin Wang, Daria Zorzi, Dario Ribero, Lee M. Ellis, Katrina Y. Glover, Robert A. Wolff, Steven A. Curley, Eddie K. Abdalla, Jean-Nicolas Vauthey
Journal: Journal of Clinical Oncology (2008)

The primary goal of this study was to evaluate whether pathologic response to chemotherapy predicts patient survival after preoperative chemotherapy and resection of colorectal liver metastases (CLM). The secondary goal of the study was to identify the clinical predictors of pathologic response.A retrospective review was performed of 305 patients who underwent preoperative irinotecan- or oxaliplatin-based chemotherapy, followed by resection of CLM. Pathologic response was systematically evaluated and reported as the mean of the percentage of cancer cells remaining within each tumor. Univariate and multivariate analyses were performed to identify the predictors of pathologic response and survival.Cumulative 5-year overall survival rates by pathologic response status were as follows: 75% complete response (no residual cancer cells), 56% major response (1% to 49% residual cancer cells), and 33% minor response (> or = 50% residual cancer cells; complete v major response, P = .037; major v minor response, P = .028). Multivariate analysis revealed that only surgical margin status (P = .050; hazard ratio [HR], 1.77) and pathologic response (major response: P = .034; HR, 4.80; minor response: P = .007; HR, 6.93) were independent predictors of survival. Multivariate analysis of the predictors of pathologic response revealed that carcinoembryonic antigen level < or = 5 ng/mL, tumor size < or = 3 cm, and chemotherapy with fluoropyrimidine plus oxaliplatin and bevacizumab were independent predictors of pathologic response.Pathologic response predicts survival after preoperative chemotherapy and resection of CLM. Degree of pathologic response represents a new outcome end point for prognosis after resection of CLM.
Desmoglein 1 deficiency results in severe dermatitis, multiple allergies and metabolic wasting
Authors: Liat Samuelov, Ofer Sarig, Robert M Harmon, Debora Rapaport, Akemi Ishida-Yamamoto, Ofer Isakov, Jennifer L Koetsier, Andrea Gat, Ilan Goldberg, Reuven Bergman, Ronen Spiegel, Ori Eytan, Shamir Geller, Sarit Peleg, Noam Shomron, Christabelle S M Goh, Neil J Wilson, Frances J D Smith, Elizabeth Pohler, Michael A Simpson, W H Irwin McLean, Alan D Irvine, Mia Horowitz, John A McGrath, Kathleen J Green, Eli Sprecher
Journal: Nature Genetics (2013)