tbuckley/cabot-search huggingface dataset:
Sox5 and c-Maf cooperatively induce Th17 cell differentiation via RORγt induction as downstream targets of Stat3
Authors: Shigeru Tanaka, Akira Suto, Taro Iwamoto, Daisuke Kashiwakuma, Shin-ichiro Kagami, Kotaro Suzuki, Hiroaki Takatori, Tomohiro Tamachi, Koichi Hirose, Atsushi Onodera, Junpei Suzuki, Osamu Ohara, Masakatsu Yamashita, Toshinori Nakayama, Hiroshi Nakajima
Journal: The Journal of Experimental Medicine (2014)

Stat3 signaling is essential for the induction of RORγt and subsequent Th17 cell differentiation. However, the downstream targets of Stat3 for RORγt expression remain largely unknown. We show here that a novel isoform of Sox5, named Sox5t, is induced in Th17 cells in a Stat3-dependent manner. In vivo, T cell-specific Sox5-deficient mice exhibit impaired Th17 cell differentiation and are resistant to experimental autoimmune encephalomyelitis and delayed-type hypersensitivity. Retrovirus-mediated induction of Sox5 together with c-Maf induces Th17 cell differentiation even in Stat3-deficient CD4(+) T cells but not in RORγt-deficient CD4(+) T cells, indicating that Sox5 and c-Maf induce Th17 cell differentiation as downstream effectors of Stat3 and as upstream inducers of RORγt. Moreover, Sox5 physically associates with c-Maf via the HMG domain of Sox5 and DNA-binding domain of c-Maf, and Sox5 together with c-Maf directly activates the promoter of RORγt in CD4(+) T cells. Collectively, our results suggest that Sox5 and c-Maf cooperatively induce Th17 cell differentiation via the induction of RORγt as downstream targets of Stat3.
Multidrug Resistance–Linked Gene Signature Predicts Overall Survival of Patients with Primary Ovarian Serous Carcinoma
Authors: Jean-Pierre Gillet, Anna Maria Calcagno, Sudhir Varma, Ben Davidson, Mari Bunkholt Elstrand, Ram Ganapathi, Aparna A. Kamat, Anil K. Sood, Suresh V. Ambudkar, Michael V. Seiden, Bo R. Rueda, Michael M. Gottesman
Journal: Clinical Cancer Research (2012)

This study assesses the ability of multidrug resistance (MDR)-associated gene expression patterns to predict survival in patients with newly diagnosed carcinoma of the ovary. The scope of this research differs substantially from that of previous reports, as a very large set of genes was evaluated whose expression has been shown to affect response to chemotherapy.
Carbohydrate metabolism in hepatocellular carcinoma: Where does the glucose go?
Authors: Giulio Marchesini, Gianpaolo Bianchi
Journal: Hepatology (1989)

Fourteen normal controls, eleven patients with non-alcoholic cirrhosis, twenty-nine with hepatocellular carcinoma (HCC) and six with HCC and hypoglycemia were studied. The tests performed include iv glucose tolerance test (25 g) and glucagon challenge test (2 mg). In cirrhosis, glucose intolerance and insulin resistance were demonstrated. The fasting hyperinsulinemia in cirrhosis is the result of decreased degradation as shown by the normal fasting C-peptide. The increased insulin responses to glucose, despite a normal C-peptide response, further supports the importance of impaired degradation in the pathogenesis of hyperinsulinemia after challenge. Despite a strong etiological association between cirrhosis and HCC, patients with HCC do not have significant hyperinsulinemia or glucose intolerance. This provides metabolic evidence to support the clinico-pathological observation that HCC patients with clinically overt hypoglycemia, the fasting glucose, insulin and C-peptide were very low. the C-peptide responses to glucose and glucagon challenges were suppressed despite pharmacologic stimulation. this can be explained by the suppression of insulin secretion by a circulating substance secreted by heptoma. the results support the pathogenetic importance of insulinlike activities recently detected in HCC patients with hypoglycemia.
Host and Environmental Factors Enhancing Carcinogenesis in the Respiratory Tract
Authors: P Nettesheim, D C Topping, R Jamasbi
Journal: The Annual Review of Pharmacology and Toxicology (1981)

Particularly in deaing with occupational lung cancer, it is often difficult to identify the major causative agent(s) or cofactor(s) in the complex work environment. The problem is further compounded by various factors that may predispose individuals or groups of individuals to the development of cancer. Among the factors that have to be considered are the genetic control of drug metabolism, and a number of genetic aberrations. Similarly, various acquired diseases and physiological or nutritional states have been implicated in certain types of cancer, though precise interrelationships have not been defined. Over the past 10 years, our laboratory has been engaged in studies concerned with the pathogenesis of lung cancer, with particular attention given to the possible interaction of multiple endogenous and exogenous factors. Those studies and major contributions made by other investigators which might have a bearing on the problem of the multifactor etiology of lung cancer are reviewed. Experiments relating to modification of host susceptibility and studies concerned with the interaction of environmental or occupational agents are discussed.
"Polycythaemia Hypertonica": Is Polycythaemia A Somewhat Favourable Sign in High Blood Pressure Cases ?
Authors: F. P. Weber
Journal: BMJ (1927)

JULY i6, Ig271 " POLYCYTHAEMIA HYPERTONICA."rzBamOB as much as possible in the open air.Where conditions are bad, the disease cani best be held in check by preventing accumulation of secretions.The child should be made to lhang over the bedside every miorning and eveniing so that the cavities may draini to the greatest advantage.The position alone is eniouglh to start the cough.Sinice putre- factioni of the sputumiis one of the most distressing features, vigorous attempts at disinfection should be made.Tlhe methods are:1.By enclosing the lpatient in a chamber satulated with tlhe vapour of creosote or somne similar disinfectanit, for increasing periods of time.
Spotlight on mechanisms of vascular inflammation
Authors: F. Sanchez-Madrid, W. C. Sessa
Journal: Cardiovascular Research (2010)

Understanding the complexity of the inflammatory response is of critical importance in the search for effective therapies for common vascular chronic inflammatory and autoimmune diseases with high morbidity and mortality rates worldwide. This spotlight issue is devoted to reviewing knowledge accumulated over the past few years on the molecular and cellular mechanisms operating in vascular inflammation. Throughout the issue there is also a discussion of current animal models of inflammatory vascular diseases in terms of their similarities and differences in comparison with human conditions.

A general overview of the molecular and cellular actors involved in the inflammatory response is provided by Barreiro et al .1 The analysis begins at the molecular level, describing the soluble factors and the adhesion and chemotactic receptors that orchestrate the various steps of leucocyte recruitment during inflammation. The cellular structures that are required to mediate the contact between leucocytes and endothelial cells during extravasation2 are also reviewed. Finally, Barreiro et al . discuss the guidance of different leucocyte subsets (Th1, Th2, Th17, Treg, cDC, pDC, Gr1+ inflammatory monocytes, etc.) to specific inflammatory scenarios and the potential of therapeutic strategies based on the blockade of leucocyte guidance.

The theme of guidance is continued by Kubes et al. ,3 who discuss the molecular mechanisms underlying leucocyte chemotaxis, comparing in vivo and in vitro models. Immune cells need to migrate in a directed manner to arrive promptly at inflammation sites. During this process, leucocytes establish contacts with and adhere to activated endothelium and then crawl towards a suitable site for extravasation. Integrin-based adhesion is regulated by chemokines via Rap GTPases and their guanine-nucleotide exchange factors such as CalDAG-GEF1; in contrast, intraluminal crawling by leucocytes is governed by β2 integrins and also seems to be Vav-1 dependent. Once leucocytes traverse the endothelium, they have to … 

*Corresponding author. Tel: +34 913 092 115; fax: +34 915 202 374, Email: fsanchez.hlpr{at}salud.madrid.org
Extracorporeal shock wave lithotripsy of gall stones: an in vitro comparison between an electrohydraulic and a piezoceramic device.
Authors: R Schachler, N C Bird, T Sauerbruch, E A Frost, M Sackmann, G Paumgartner, A G Johnson
Journal: Gut (1991)

A comparative study of the effectiveness of two types of lithotripter in fragmenting gall bladder stones is reported. The machines used were a Piezolith 2300, which generates shock waves by the piezoceramic principle, and a Dornier MPL 9000, which produces the shock waves by underwater spark discharge. With each machine, corresponding stones of 45 pairs of weight and volume matched calculi (median volume 0.5 cm3, median diameter 10.5 mm) obtained at cholecystectomy were treated. All stones were successfully disintegrated (fragments smaller than 2 mm) with up to 5400 (median 628) shocks with the Piezolith and 3450 (median 428) shocks with the MPL 9000 lithotripters. With the Piezolith, operating at the highest power setting, a 1.65 fold median higher number of shocks was required for stone fragmentation than with the MPL 9000 at a medium power setting. Stone volume seemed to be the only determinant which affected ease of fragmentation; composition and density of the stones as assessed by computed tomography did not seem to be governing factors.
The grand challenges of the Gates Foundation: what impact on global child health?
Authors: J. M Litzow
Journal: Journal of the Royal Society of Medicine (2006)

Millions of children in poor countries die each year from preventable diseases.1 This is not news. Since their inception, international organizations including the World Health Organization (WHO) and the United Nations (UN), have dedicated countless hours and millions of dollars to alleviating this problem. More recently, a number of private foundations have become active in the work of childhood survival. The Bill and Melinda Gates Foundation, one of the leading financial supporters of global health, recently announced over US$ 450 million to be distributed in grants to 43 projects that address the Foundation's 14 Grand Challenges (Box 1).2 The programme aims to stimulate the creation of novel ways to prevent, treat and cure the diseases that kill millions of people each year in developing countries.

In this paper we will explore the potential impact of some of goals of the Grand Challenges for global child health within the context of current international health initiatives including the Integrated Management of Child Diseases created by the WHO and UNICEF, the UN's Millennium Development Goals, and the Bellagio Study Group's assessment of the current state of global child survival in the developing world.
COCCIDIOIDAL GRANULOMA: REPORT OF A CASE
Authors: J. F. BURGESS
Journal: British Journal of Dermatology (1929)

Journal Article COCCIDIOIDAL GRANULOMA: REPORT OF A CASE Get access J. F. BURGESS, M.B. J. F. BURGESS, M.B. Dermatologist to the Montreal General Hospital; Lecturer on Dermatology, McGill University, Montreal Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 41, Issue 4, 1 April 1929, Pages 145–148, https://doi.org/10.1111/j.1365-2133.1929.tb09326.x Published: 01 April 1929
Aseptic arthritis after gonorrhoea.
Authors: L Rosenthal, B Olhagen, S Ek
Journal: Annals of the Rheumatic Diseases (1980)

Sixteen patients with aseptic arthritis developing after gonorrhoea and 14 patients with arthritis after nongonococcal urogenital infection have been analysed with respect to clinical course, roentgenological signs, and humoral as well as cellular immune responses to Neisseria gonorrhoeae antigen. Fifty-eight healthy blood donors were used as controls. The clinical pattern did not differ significantly between the 2 groups. Eye or skin lesions indicative of Reiter's syndrome were found in 5 patients of both groups. Signs of sacroiliac arthritis were found in 8 and 6 patients respectively. Gonococcal complement fixation was positive in 9 of 16 patients in the postgonorrhoeal arthritis group and in 0 of 14 patients in the arthritis group with nongonococcal urogenital infection. The lymphocyte stimulation induced by gonococcal antigen was significantly greater in patients with postgonorrhoeal arthritis than in healthy controls. When reference was made to the results of stimulation of the lymphocytes with PPD, there was also a significant difference in the lymphocyte reactivity to gonococcal antigen between the group of patients with postgonorrhoeal arthritis and that of patients with arthritis after non-gonococcal urogenital infection. No such difference was noted between the latter group and the healthy controls. The clinical and immunologic data argue in favour of the hypothesis that Neisseria gonorrhoeae may induce an aseptic arthritis which sometimes presents as a complete Reiter's syndrome.
Prothrombin Concentrates in Treatment of Christmas Disease and Allied Disorders
Authors: Francis A. Breen
Journal: JAMA (1969)

Chromatographic DEAE-adsorbed prothrombin complex (Hemoplex) was administered to 14 patients with disorders involving depression in the levels of factors II, VII, IX, and X. These included patients with Christmas disease, liver disease, and hypoprothrombinemia induced by bishydroxycoumarin (Dicumarol). In every instance, prompt hemostasis was achieved as evidenced by cessation of hemorrhage and correction of procoagulant deficits. A frequently seen immediate improvement in hemostasis was attributed to the presence of activated surface factor. Limited usage of tricalcium phosphate adsorbed prothrombin complex failed to show significant improvement in subsequent levels of circulating factor IX.
Repression of B-Cell Linker (BLNK) and B-Cell Adaptor for Phosphoinositide 3-Kinase (BCAP) Is Important for Lymphocyte Transformation by Rel Proteins
Authors: Nupur Gupta, Jeffrey Delrow, Amar Drawid, Anirvan M. Sengupta, Gaofeng Fan, Céline Gélinas
Journal: Cancer Research (2008)

Abstract Persistent Rel/nuclear factor-κB (NF-κB) activity is a hallmark of many human cancers, and the Rel proteins are implicated in leukemia/lymphomagenesis but the mechanism is not fully understood. Microarray analysis to identify transformation-impacting genes regulated by NF-κB's oncogenic v-Rel and c-Rel proteins uncovered that Rel protein expression leads to transcriptional repression of key B-cell receptor (BCR) components and signaling molecules like B-cell linker (BLNK), the B-cell adaptor for phosphoinositide 3-kinase (BCAP) and immunoglobulin λ light chain (Igλ), and is accompanied by a block in BCR-mediated activation of extracellular signal-regulated kinase, Akt, and c-Jun-NH2-kinase in response to anti-IgM. The BLNK and BCAP proteins were also down-regulated in lymphoid cells expressing a transformation-competent chimeric RelA/v-Rel protein, suggesting a correlation with the capacity of Rel proteins to transform lymphocytes. DNA-binding studies identified functional NF-κB–binding sites, and chromatin immunoprecipitation (ChIP) data showed binding of Rel to the endogenous blnk and bcap promoters in vivo. Importantly, restoration of either BLNK or BCAP expression strongly inhibited transformation of primary chicken lymphocytes by the potent NF-κB oncoprotein v-Rel. These findings are interesting because blnk and other BCR components and signaling molecules are down-regulated in primary mediastinal large B-cell lymphomas and Hodgkin's lymphomas, which depend on c-Rel for survival, and are consistent with the tumor suppressor function of BLNK. Overall, our results indicate that down-regulation of BLNK and BCAP is an important contributing factor to the malignant transformation of lymphocytes by Rel and suggest that gene repression may be as important as transcriptional activation for Rel's transforming activity. [Cancer Res 2008;68(3):808–14]
How does diesel exhaust impact asthma?
Authors: J. R. Balmes
Journal: Thorax (2010)

However, undoubtedly the use of echocardiography (including transoesophageal echocardiography), laboratory findings and venous ultrasonography should be encouraged in patients with suspected high-risk PE.Management decisions should be taken based on all collected data on a case by case basis.Each test comes to the rescue of the others.'One for all and all for one'.
Mutations of the KISS1 Gene Associated with Central Precocious Puberty
Authors: L. F. G. Silveira, S. D. Noel, A. P. Silveira-Neto, A. P. Abreu, V. N. Brito, M. AG. Santos, S. D. C. Bianco, W. Kuohung, S. Xu, M. Gryngarten, M. E. Escobar, I. J. P. Arnhold, B. B. Mendonca, U. B. Kaiser, A. C. Latronico
Journal: Endocrine Reviews (2010)

Kisspeptin, encoded by the KISS1 gene, is a key stimulatory factor of GnRH secretion and puberty onset. Inactivating mutations of its receptor (KISS1R) cause isolated hypogonadotropic hypogonadism (IHH). A unique KISS1R activating mutation was described in central precocious puberty (CPP). To investigate KISS1 mutations in patients with idiopathic CPP and normosmic IHH. Eighty-three children with CPP (77 girls) and 61 patients with IHH (40 men) were studied. The control group consisted of 200 individuals with normal pubertal development. The promoter region and the 3 exons of KISS1 were amplified and sequenced. Cells expressing KISS1R were stimulated with synthetic human wild-type or mutant kisspeptin-54 (kp54) and inositol phosphate accumulation was measured. In a second set of experiments, kp54 was pre-incubated in human serum prior to stimulation of the cells. Two novel KISS1 missense mutations, p.P74S and p.H90D, were identified in three unrelated children with idiopathic CPP. Both mutations were absent in 400 control alleles. The p.P74S mutation was identified in the heterozygous state in a boy who developed CPP at 1 yr of age. The p.H90D mutation was identified in the homozygous state in two unrelated girls with CPP. In vitro studies revealed that the capacity of the P74S and H90D mutants to stimulate IP production was similar to the wild-type. After pre-incubation of wild-type and mutant kp54’s in human serum, the capacity to stimulate signal transduction was significantly greater for P74S compared to the wild-type, suggesting that the p.P74S variant is more stable. Only polymorphisms were found in the IHH group. Two KISS1 mutations were identified in unrelated patients with idiopathic CPP. The p.P74S variant was associated with higher kisspeptin resistance to degradation in comparison to the wild-type, suggesting a role for this mutation in the precocious puberty phenotype.
Nuclear Chromosome Dynamics in the Drosophila Male Germ Line Contribute to the Nonrandom Genomic Distribution of Retrogenes
Authors: Carlos Díaz-Castillo, José M. Ranz
Journal: Molecular Biology and Evolution (2012)

The origin of RNA-based gene duplicates, that is, retrogenes, involves the reverse transcription of an mRNA derived from a parental gene to generate a cDNA copy, its insertion elsewhere in the genome, and the recruitment of regulatory sequences. Drosophila retrogenes are preferentially expressed in testis and a higher than expected number transpose to autosomal locations from the X chromosome. However, the influence of genomic context on the insertion preference of retrogenes remains poorly understood. We find that the distribution of retrogenes in the Drosophila melanogaster genome can be explained by an insertion bias toward chromosome domains containing testis-biased genes that are located at the nuclear periphery in somatic cells, but at inner positions in the male germ line. The lower fraction of these chromosome domains accessible in the male germ line on the X chromosome as compared with the autosomes also contributes to the scarcity of retrogenes on the X chromosome.
Assessment of Temperature, Proximity, and Course of the Esophagus During Radiofrequency Ablation Within the Left Atrium
Authors: Jennifer E. Cummings, Robert A. Schweikert, Walid I. Saliba, J. David Burkhardt, Johannes Brachmann, Jens Gunther, Volker Schibgilla, Atul Verma, MarkAlain Dery, John L. Drago, Fethi Kilicaslan, Andrea Natale
Journal: Circulation (2005)

Left atrioesophageal fistula is a devastating complication of atrial fibrillation ablation. There is no standard approach for avoiding this complication, which is caused by thermal injury during ablation. The objectives of this study were to evaluate the course of the esophagus and the temperature within the esophagus during pulmonary vein antrum isolation (PVAI) and correlate these data with esophagus tissue damage.Eight-one patients presenting for PVAI underwent esophagus evaluation that included temperature probe placement. Esophagus course was obtained with computed tomography, 3D imaging (NAVX), or intracardiac echocardiography. For each lesion, the power, catheter and esophagus temperature, location, and presence of microbubbles were recorded. Lesion location and esophagus course were defined with 6 predetermined left atrial anatomic segments. Endoscopy evaluated tissue changes during and after PVAI. Of 81 patients, the esophagus coursed near the right pulmonary veins in 23 (28.4%), left pulmonary veins in 31 (38.3%), and mid-posterior wall in 27 (33%). Esophagus temperature was significantly higher during left atrial lesions along its course than with lesions elsewhere (38.9+/-1.4 degrees C, 36.8+/-0.5 degrees C, P<0.01). Lesions that generated microbubbles had higher esophagus temperatures than those without (39.3+/-1.5 degrees C, 38.5+/-0.9 degrees C, P<0.01). Power was not predictive of esophagus temperatures. Distance between the esophagus and left atrium was 4.4+/-1.2 mm.Lesions near the course of the esophagus that generated microbubbles significantly increased esophagus temperature compared with lesions that did not. Power did not correlate with esophagus temperatures. Esophagus variability makes the avoidance of lesions along its course difficult. Rather than avoiding posterior lesions, emphasis could be placed on better esophagus monitoring for creation of safer lesions.
Who Is Tested for Diabetic Kidney Disease and Who Initiates Treatment?
Authors: Susan L. Johnson, Edward F. Tierney, Kingsley U. Onyemere, Chien-Wen Tseng, Monica M. Safford, Andrew J. Karter, Assiamira Ferrara, O. Kenrick Duru, Arleen F. Brown, K.M. Venkat Narayan, Theodore J. Thompson, William H. Herman
Journal: Diabetes Care (2006)

We examined factors associated with screening for albuminuria and initiation of ACE inhibitor or angiotensin receptor blocker (ARB) treatment in diabetic patients.We conducted surveys and medical record reviews for 5,378 patients participating in a study of diabetes care in managed care at baseline (2000-2001) and follow-up (2002-2003). Factors associated with testing for albuminuria were examined in cross-sectional analysis at baseline. Factors associated with initiating ACE inhibitor/ARB therapy were determined prospectively.At baseline, 52% of patients not receiving ACE inhibitor/ARB therapy and without known diabetic kidney disease (DKD) were screened for albuminuria. Patients > or =65 years of age, those with higher HbA(1c), those with cardiovascular disease (CVD), and those without hyperlipidemia were less likely to be screened. Of the patients with positive screening tests, 47% began ACE inhibitor/ARB therapy. Initiation of therapy was associated with positive screening test results, BMI > or =25 kg/m(2), treatment with insulin or oral antidiabetic agents, peripheral neuropathy, systolic blood pressure > or =140 mmHg, and CVD. Of the patients receiving ACE inhibitor/ARB therapy or with known DKD, 63% were tested for albuminuria.Screening for albuminuria was inadequate, especially in older patients or those with competing medical concerns. The value of screening could be increased if more patients with positive screening tests initiated ACE inhibitor/ARB therapy. The efficiency of screening could be improved by limiting screening to diabetic patients not receiving ACE inhibitor/ARB therapy and without known DKD.