tbuckley/cabot-search huggingface dataset:
The Effect of Diesel Exhaust Particles on Pathogen-associated Molecular Patterns-induced Cytokine Generation from Bronchial Epithelial Cells
Authors: H. Nagase, H. Takano, K. Inoue, A. Hara, Y. Kojima, M. Suzukawa, M. Kuramochi, H. Ishida, T. Adachi, N. Suzuki
Journal: Journal of Allergy and Clinical Immunology (2009)
Identification of the Receptor Tyrosine Kinase c-Met and Its Ligand, Hepatocyte Growth Factor, as Therapeutic Targets in Clear Cell Sarcoma
Authors: Ian J. Davis, Andrew W. McFadden, Yixiang Zhang, Angela Coxon, Teresa L. Burgess, Andrew J. Wagner, David E. Fisher
Journal: Cancer Research (2010)

Abstract Clear cell sarcoma (CCS), a childhood tumor of the tendons and aponeuroses, is uniformly fatal once it has metastasized because of its profound therapeutic resistance. CCS is characterized by production of a chimeric transcription factor, EWS-ATF1, which is formed as the result of a disease-specific chromosomal translocation. EWS-ATF1 activates the melanocyte transcription factor MITF, which in turn activates transcription of c-Met, an oncogenic receptor tyrosine kinase recently shown to be activated in CCS. Based on this connection, we hypothesized that c-Met inhibition may offer a strategy to treat CCS, as an indirect tactic to defeat a transforming pathway downstream of EWS-ATF1. Here, we show that primary CCS and CCS-derived cell lines express c-Met, which is activated in an autocrine fashion by its ligand hepatocyte growth factor (HGF)/scatter factor in some CCS cell lines. c-Met expression is critical for CCS invasion, chemotaxis, and survival. Blocking c-Met activity with a small-molecule inhibitor (SU11274) or a neutralizing antibody to its ligand HGF (AMG 102) significantly reduced CCS cell growth in culture. Similarly, AMG 102 significantly suppressed in vivo tumor growth in an autocrine xenograft model of CCS. Collectively, these findings suggest the HGF:c-Met signaling axis as a candidate therapeutic target to improve clinical management of CCS. Cancer Res; 70(2); 639–45
Taxane-Based Combinations As Adjuvant Chemotherapy of Early Breast Cancer: A Meta-Analysis of Randomized Trials
Authors: Michele De Laurentiis, Giuseppe Cancello, Diego D'Agostino, Mario Giuliano, Antonio Giordano, Emilia Montagna, Rossella Lauria, Valeria Forestieri, Angela Esposito, Lucrezia Silvestro, Roberta Pennacchio, Carmen Criscitiello, Agnese Montanino, Gennaro Limite, Angelo Raffaele Bianco, Sabino De Placido
Journal: Journal of Clinical Oncology (2007)

Purpose We conducted a meta-analysis of randomized trials that evaluated the efficacy of incorporating taxanes into anthracycline-based regimens for early breast cancer (EBC). We aimed to determine whether this approach improves disease-free survival (DFS) and overall survival (OS) and whether benefits are maintained across relevant patient subgroups. Methods Studies were retrieved by searching the PubMed database and the proceedings of major conferences. We extracted hazard ratios (HR) and 95% CIs for DFS and OS from each trial and obtained pooled estimates using an inverse-variance model. Results Thirteen studies were included in the meta-analysis (N = 22,903 patients). The pooled HR estimate was 0.83 (95% CI, 0.79 to 0.87; P &lt; .00001) for DFS and 0.85 (95% CI, 0.79 to 0.91; P &lt; .00001) for OS. Risk reduction was not influenced by the type of taxane, by estrogen receptor (ER) expression, by the number of axillary metastases (N1 to 3 v N4+), or by the patient's age/menopausal status. Sensitivity analysis showed that taxanes given in combination with anthracyclines, unlike sequential administration, did not significantly improve OS. However, the test for interaction showed that HR did not differ between the two schedules (P = .54). Taxane administration resulted in an absolute 5-year risk reduction of 5% for DFS and 3% for OS. Conclusion The addition of a taxane to an anthracycline-based regimen improves the DFS and OS of high-risk EBC patients. The DFS benefit was independent of ER expression, degree of nodal involvement, type of taxane, age/menopausal status of patient, and administration schedule.
Hypothalamic-pituitary-gonadal function in men with cirrhosis of the liver.
Authors: N A Mowat, C R Edwards, R Fisher, A S McNeilly, J R Green, A M Dawson
Journal: Gut (1976)

Hypothalamic-pituitary-gonadal function was studied in 37 cirrhotic males, 25 of whom were alcoholic. Irrespective of aetiology, cirrhotic patients had significantly reduced free testosterone concentrations. Despite low free testosterone concentrations and reduced or absent spermatogenesis, basal levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) were normal in nearly all patients, suggesting impaired function of the hypothalamic-pituitary-gonadal axis. In 14 cirrhotic men, seven of whom had gynaecomastia, the ability of the pituitary to secrete LH and FSH in response to exogenous gonadotrophin releasing-hormone (LH/FSH-RH) was asssessed. A normal LH response to LH/FSH-RH was obtained in patients without gynaecomastia. An exaggerated LH response was found in four of seven with gynaecomastia, suggesting Leydig cell failure. The Leydig cell response to exogenous gonadotrophin in eight consecutive cirrhotic patients was probably abnormal but difficult to interpret as all but one were within conventionally accepted limits of normality. The patients without gynaecomastia gave a normal or minimally exaggerated FSH response to LH/FSH-RH. Six of seven with gynaecomastia gave a markedly exaggerated response suggesting failure of spermatogenesis, and all tested were either azoospermic of oligospermic. The single patient with a normal FSH response had a normal sperm count. The pituitary cells can therefore respond to LH/RSH-RH and the Leydig cells of the testes show some response to exogenous gonadotrophin. Similar abnormalities in hypothalamic-pituitary-gonadal function have recently been described in patients with normal liver function on chronic oestrogen therapy.
Paternal Transmission of a Secondary Symbiont during Mating in the Viviparous Tsetse Fly
Authors: Linda De Vooght, Guy Caljon, Jos Van Hees, Jan Van Den Abbeele
Journal: Molecular Biology and Evolution (2015)

Sodalis glossinidius, a maternally inherited secondary symbiont of the tsetse fly, is a bacterium in the early/intermediate state of the transition toward symbiosis, representing an important model for investigating establishment and evolution of insect-bacteria symbiosis. The absence of phylogenetic congruence in tsetse-Sodalis coevolution and the existence of Sodalis genotypic diversity in field flies are suggestive for a horizontal transmission route. However, to date no natural mechanism for the horizontal transfer of this symbiont has been identified. Using novel methodologies for the stable fluorescent-labeling and introduction of modified Sodalis in tsetse flies, we unambiguously show that male-borne Sodalis is 1) horizontally transferred to females during mating and 2) subsequently vertically transmitted to the progeny, that is, paternal transmission. This mixed mode of transmission has major consequences regarding Sodalis' genome evolution as it can lead to coinfections creating opportunities for lateral gene transfer which in turn could affect the interaction with the tsetse host.
Acute asthma and antidiuretic hormone secretion.
Authors: K P Dawson, D M Fergusson, J West, C Wynne, W A Sadler
Journal: Thorax (1983)

Plasma antidiuretic hormone concentrations were measured in a group of children with acute asthma and in a control group. Very high levels of antidiuretic hormone were found in the asthmatic group. There were no changes in other biochemical indices. If overproduction of antidiuretic hormone is sustained then fluid administration to children with severe acute asthma is potentially dangerous.
Quality Cancer Care for Adolescents and Young Adults: A Position Statement
Authors: Brad Zebrack, Beth Mathews-Bradshaw, Stuart Siegel
Journal: Journal of Clinical Oncology (2010)

This consensus-based position statement on behalf of the LIVESTRONG Young Adult Alliance (Alliance) offers recommendations to enhance oncologic care of adolescent and young adult (AYA) patients with cancer.In 2005 to 2006, the National Cancer Institute and the Lance Armstrong Foundation jointly sponsored the Adolescent and Young Adult Oncology Progress Review Group (PRG). The PRG report included the directive to develop standards of care for AYA patients with cancer and to disseminate these guidelines to the community. To this end, the Alliance convened a meeting of experts (clinicians, researchers, and advocates) in June 2009 and derived this position statement.Quality care for AYAs depends on four critical elements: timely detection; efficient processes for diagnosis, initiation of treatment, and promotion of adherence; access to health care professionals who possess knowledge specific to the biomedical and psychosocial needs of this population; and research that will ultimately derive objective criteria for the development of AYA oncology care guidelines. Achieving quality care for AYAs will require assistance with management of disease and treatment effects; cognizance of the unique psychosocial context for AYA growth and development; assessment of and attention to cognitive, psychiatric, and psychosocial issues; facilitated transition to treatment care; and referral to age-appropriate information and support services.Dissemination of recommendations stated here will raise awareness of the need for AYA-specific care guidelines and assist providers in the delivery of care that is responsive to the distinct needs of AYAs with cancer.
Variants of thymic stromal lymphopoietin and its receptor associate with eosinophilic esophagitis
Authors: Joseph D. Sherrill, Pei-Song Gao, Emily M. Stucke, Carine Blanchard, Margaret H. Collins, Phil E. Putnam, James P. Franciosi, Jonathan P. Kushner, J. Pablo Abonia, Amal H. Assa'ad, Melinda Butsch Kovacic, Jocelyn M. Biagini Myers, Bruce S. Bochner, Hua He, Gurjit Khurana Hershey, Lisa J. Martin, Marc E. Rothenberg
Journal: Journal of Allergy and Clinical Immunology (2010)
264 IMPAIRED PANCREATIC DUODENAL HOMEOBOX PROTEIN 1 (PDX-1) EXPRESSION PROMOTES DIABETES AND HEPATOCELLULAR CARCINOMA (HCC) DEVELOPMENT IN MICE
Authors: S. De Minicis, S. Saccomanno, C. Rychlicki, L. Agostinelli, L. Trozzi, I. Pierantonelli, K. Shanmukhappa, A. Benedetti, G. Svegliati-Baroni, M. Marzioni
Journal: Journal of Hepatology (2012)
Purinergic Signaling and Blood Vessels in Health and Disease
Authors: Geoffrey Burnstock, Vera Ralevic
Journal: Pharmacological Reviews (2013)

Purinergic signaling plays important roles in control of vascular tone and remodeling. There is dual control of vascular tone by ATP released as a cotransmitter with noradrenaline from perivascular sympathetic nerves to cause vasoconstriction via P2X<sub>1</sub> receptors, whereas ATP released from endothelial cells in response to changes in blood flow (producing shear stress) or hypoxia acts on P2X and P2Y receptors on endothelial cells to produce nitric oxide and endothelium-derived hyperpolarizing factor, which dilates vessels. ATP is also released from sensory-motor nerves during antidromic reflex activity to produce relaxation of some blood vessels. In this review, we stress the differences in neural and endothelial factors in purinergic control of different blood vessels. The long-term (trophic) actions of purine and pyrimidine nucleosides and nucleotides in promoting migration and proliferation of both vascular smooth muscle and endothelial cells via P1 and P2Y receptors during angiogenesis and vessel remodeling during restenosis after angioplasty are described. The pathophysiology of blood vessels and therapeutic potential of purinergic agents in diseases, including hypertension, atherosclerosis, ischemia, thrombosis and stroke, diabetes, and migraine, is discussed.
Pervasive Developmental Disorders in Preschool Children: Confirmation of High Prevalence
Authors: Suniti Chakrabarti, Eric Fombonne
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: The rate of reported pervasive developmental disorders has increased, and the authors found a rate of 62.6 per 10,000 in a previous study of preschoolers in Stafford, U.K. They conducted another survey in 2002 to estimate the prevalence in children in a later birth cohort and to compare it to previous findings from the same area. METHOD: Screening for developmental problems included 10,903 children ages 4.0 to 6.0 years who were living in a Midlands town on the survey date. Children with symptoms suggestive of pervasive developmental disorders were intensively assessed by a multidisciplinary team using standardized diagnostic interviews, psychometric tests, and medical workups. RESULTS: Sixty-four children (85.9% boys) were diagnosed with pervasive developmental disorders. The prevalence was 58.7 per 10,000, with a 95% confidence interval (CI) of 45.2–74.9, for all pervasive developmental disorders, 22.0 per 10,000 (95% CI=14.1–32.7) for autistic disorder, and 36.7 per 10,000 (95% CI=26.2–49.9) for other variants. These rates were not significantly different from the previous rates. The mean age at diagnosis was 37.8 months, and 53.1% of the children were originally referred by health visitors. Of the 64 children with pervasive developmental disorders, 29.8% had mental retardation, but this rate varied by disorder subtype. Few children had associated medical conditions. CONCLUSIONS: The rate of pervasive developmental disorders is higher than reported 15 years ago. The rate in this study is comparable to that in previous birth cohorts from the same area and surveyed with the same methods, suggesting a stable incidence.
Neonatal exposure to thymotropic gross murine leukemia virus induces virus-specific immunologic nonresponsiveness.
Authors: J M Korostoff, M T Nakada, S J Faas, K J Blank, G N Gaulton
Journal: The Journal of Experimental Medicine (1990)

Neonatal exposure to Gross murine leukemia virus results in a profound inhibition of the virus-specific T and B cell responses of adult animals. Animals exposed to virus as neonates exhibit a marked depression in virus-specific T cell function as measured by the virtual absence of in vivo delayed type hypersensitivity responses and in vitro proliferative responses to virally infected stimulator cells. Further, serum obtained from neonatally treated mice failed to either immunoprecipitate viral proteins or neutralize virus in an in vitro plaque assay, suggesting the concurrent induction of a state of B cell hyporesponsiveness. The specificity of this effect at the levels of both T and B cells was demonstrated by the ability of neonatally treated mice to respond normally after adult challenge with either irrelevant reovirus or influenza virus. The replication of Gross virus within both stromal and lymphocytic compartments of the neonatal thymus suggests that thymic education plays a key role in the induction of immunologic nonresponsiveness to viruses.
On Natural and Artificial Vaccinations
Authors: Rolf M. Zinkernagel
Journal: Annual Review of Immunology (2003)

This review summarizes the general parameters of cell- and antibody-mediated immune protection and the basic mechanisms responsible for what we call immunological memory. From this basis, the various successes and difficulties of vaccines are evaluated with respect to the role of antigen in maintaining protective immunity. Based on the fact that in humans during the first 12-48 months maternal antibodies from milk and serum protect against classical acute childhood and other infections, the concept is developed that maternal antibodies attenuate most infections of babies and infants and turn them into effective vaccines. If this "natural vaccination" under passive protective conditions does not occur, acute childhood diseases may be severe, unless infants are actively vaccinated with conventional vaccines early enough, i.e., in synchronization with the immune system's maturation. Although vaccines are available against the classical childhood diseases, they are not available for many seemingly milder childhood infections such as gastrointestinal and respiratory infections; these may eventually trigger immunopathological diseases. These changing balances between humans and infections caused by changes in nursing habits but also in hygiene levels may well be involved in changing disease patterns including increased frequencies of certain autoimmune and degenerative diseases.
Sustained β <sub>1</sub> -Adrenergic Stimulation Modulates Cardiac Contractility by Ca <sup>2+</sup> /Calmodulin Kinase Signaling Pathway
Authors: Wang Wang, Weizhong Zhu, Shiqiang Wang, Dongmei Yang, Michael T. Crow, Rui-Ping Xiao, Heping Cheng
Journal: Circulation Research (2004)

A tenet of beta1-adrenergic receptor (beta1AR) signaling is that stimulation of the receptor activates the adenylate cyclase-cAMP-protein kinase A (PKA) pathway, resulting in positive inotropic and relaxant effects in the heart. However, recent studies have suggested the involvement of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in beta1AR-stimulated cardiac apoptosis. In this study, we determined roles of CaMKII and PKA in sustained versus short-term beta1AR modulation of excitation-contraction (E-C) coupling in cardiac myocytes. Short-term (10-minute) and sustained (24-hour) beta1AR stimulation with norepinephrine similarly enhanced cell contraction and Ca2+ transients, in contrast to anticipated receptor desensitization. More importantly, the sustained responses were largely PKA-independent, and were sensitive to specific CaMKII inhibitors or adenoviral expression of a dominant-negative CaMKII mutant. Biochemical assays revealed that a progressive and persistent CaMKII activation was associated with a rapid desensitization of the cAMP/PKA signaling. Concomitantly, phosphorylation of phospholamban, an SR Ca2+ cycling regulatory protein, was shifted from its PKA site (16Ser) to CaMKII site (17Thr). Thus, beta1AR stimulation activates dual signaling pathways mediated by cAMP/PKA and CaMKII, the former undergoing desensitization and the latter exhibiting sensitization. This finding may bear important etiological and therapeutical ramifications in understanding beta1AR signaling in chronic heart failure.
Molecular Mechanism for Elevation of Asymmetric Dimethylarginine and Its Role for Hypertension in Chronic Kidney Disease
Authors: Kyoko Matsuguma, Seiji Ueda, Sho-ichi Yamagishi, Yuriko Matsumoto, Utako Kaneyuki, Ryo Shibata, Toshiko Fujimura, Hidehiro Matsuoka, Masumi Kimoto, Seiya Kato, Tsutomu Imaizumi, Seiya Okuda
Journal: Journal of the American Society of Nephrology (2006)

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase. ADMA is generated by protein methyltransferase (PRMT) and is metabolized mainly by dimethylarginine dimethylaminohydrolase (DDAH). ADMA levels are reported to increase in patients with chronic kidney disease (CKD), thereby playing a role in the pathogenesis of accelerated atherosclerosis in this population. However, the precise mechanism underlying ADMA accumulation in these patients is not fully understood. This study investigated the molecular mechanism for the elevation of ADMA levels in CKD, using a rat remnant kidney model that represents progressive CKD. After male Sprague-Dawley rats underwent baseline measurement of BP and renal function, 5/6 subtotal nephrectomy (5/6Nx) and 4/6 nephrectomy were performed. Plasma and urinary levels of ADMA and symmetric dimethylarginine, an inert isomer of ADMA, were measured by HPLC. Expression levels of PRMT genes and DDAH proteins were analyzed by semiquantitative reverse transcription-PCR and Western blotting, respectively. Plasma ADMA levels were elevated in the Nx groups in proportion to the degree of nephrectomy despite marked increases in renal clearance of ADMA. In contrast, renal clearance of symmetric dimethylarginine was decreased and its plasma levels were increased in the Nx groups. Furthermore, both liver and kidney gene expression of PRMT was increased, whereas DDAH protein expression was decreased in the 5/6Nx group. Plasma ADMA levels were correlated with systolic BP levels. Moreover, adenovirus-mediated DDAH gene transfer into the 5/6Nx rats prevented the elevation of BP levels, which was associated with the reduction of plasma and urinary ADMA levels. The results presented here suggest that decreased DDAH levels as well as increased PRMT gene expression could cause the elevation of plasma ADMA levels, thereby eliciting hypertension in CKD. Substitution of DDAH protein or enhancement of its activity may become a novel therapeutic strategy for the treatment of hypertension-related vascular injury in CKD.
Thyroid hormones and the gut.
Authors: W R Middleton
Journal: Gut (1971)

Progress reportThyroid hormones and the gut Thyroid hormones have an effect on the gastrointestinal tract at all levels of organization and clinicians have long recognized the associations that exist between gastrointestinal symptoms and thyroid disease.Our present know- ledge of the mechanisms by which thyroid hormones act on the gut is, how- ever, fragmentary and much of the literature which deals with disturbances in gastrointestinal physiology in hyper-and hypothyroidism is inconclusive." 2 This review is brief and makes no attempt to be comprehensive.It is intended to illustrate some aspects of the effects of altered thyroid function on the gastrointestinal tract rather than to dwell on the biochemical role of thyroid hormones at the cellular and subcellular level-a subject recently reviewed elsewhere.3Patients with hyperthyroidism or hypothyroidism and symptoms referable to the alimentary tract rarely regard these symptoms as major complaints.This may explain the paucity of studies relating gastrointestinal disturbances to thyroid disease.Changes in appetite, however, are commonly noted by patients, and whereas hyperthyroid patients tend to develop hyperphagia, hypothyroid patients more frequently decrease their food intake.Apart from these changes in diet the commonest gut-related complaints reported in thyroid diseases are undoubtedly those due to disordered bowel function- in particular alteration in bowel habit. The Stomach in Thyroid DiseasesNeither hyperthyroidism nor hypothyroidism is associated with consistent gross pathological changes in the stomach.Studies from many centres con- firm, however, that alterations in gastric structure and function may accom- pany thyroid disease.The level of gastric acid secretion has been reported to vary greatly with both hyper-and hypothyroid states, depending to some extent upon the experimental animal studied.In man, hyperthyroidism is frequently associated with histological gastritis and with diminished acid output4'5 which may amount to achlorhydria.These abnormalities tend to return towards normal as the hyperthyroidism is controlled.5'6In the in- dividual patient the correlation between histological changes in the stomach and alterations in hydrochloric acid secretion is far from absolute and the mechanism by which hydrochloric acid secretion is reduced in thyrotoxicosis is not clear.5In spite of the normal or low gastric acid production in thyro- toxicosis at least one study7 has reported an increased incidence of duodenal ulceration.This association was not confirmed, however, in a review of 9,618 patients with hyperthyroidism.8The rate at which the stomach empties its contents into the duodenum depends to some extent upon the level of circulating thyroid hormone.This important factor must be considered when assessing intestinal absorption following oral administration of test substances, eg, a glucose tolerance test.The stomach empties rapidly in hyperthyroidism, 9,10,1112 whilst in hypo- thyroidism gastric emptying is prolonged."These alterations in gastric on August 21,
Galectin-9-CD44 Interaction Enhances Stability and Function of Adaptive Regulatory T Cells
Authors: Chuan Wu, Theresa Thalhamer, Rafael F. Franca, Sheng Xiao, Chao Wang, Chie Hotta, Chen Zhu, Mitsuomi Hirashima, Ana C. Anderson, Vijay K. Kuchroo
Journal: Immunity (2014)