tbuckley/cabot-search huggingface dataset:
Dynamics of spread of HIV-I infection in a rural district of Uganda.
Authors: M J Wawer, D Serwadda, S D Musgrave, J K Konde-Lule, M Musagara, N K Sewankambo
Journal: BMJ (1991)

OBJECTIVE--To define the geographical distribution of HIV infection and the community characteristics associated with HIV prevalence in a rural population of Uganda. DESIGN--Seroprevalence survey and interviews of the population aged 13 years and older in 21 randomly selected clusters. SETTING--Rural population of Rakai district, south west Uganda. SUBJECTS--1292 adults, of whom 594 men and 698 women gave a blood sample and answered the questionnaire. MAIN OUTCOME MEASURES--HIV status determined by ELISA and western blotting in relation to community characteristics. RESULTS--The weighted seroprevalence of HIV for the district was 12.6% with prevalence by cluster varying from 1.2% to 52.8%. Seroprevalence was highest in main road trading centres (men 26%, women 47%), intermediate in rural trading villages on secondary roads (men 22%, women 29%), and lowest in rural agricultural villages (men 8%, women 9%). For both men and women, multiple regression showed a strong negative association between cluster seroprevalence and the proportion of the population employed in agriculture (beta = -0.677 for men, -0.807 for women). Among women, cluster seroprevalence increased with a higher proportion of the population reporting multiple sex partners (beta = 0.814), external travel (beta = 0.579), and injections (beta = 0.483). CONCLUSIONS--Community characteristics, particularly the proportion of the population in agriculture, are associated with HIV prevalence and can be used for targeting interventions. The seroprevalences of HIV suggest spread of infection from main road trading centres, through intermediate trading villages, to rural agricultural villages.
PTU-097 A ‘Real-Life’ Picture of Abnormal Liver Function Test Management in Primary Care in Hull, East Yorkshire
Authors: B Williams, G Abouda, M Follows
Journal: Gut (2013)

<h3>Introduction</h3> As part of a community based pilot study looking at NAFLD and Enhanced Liver Fibrosis (ELF) testing (COMMANDS), an audit of GP management of Abnormal Liver Function (LFT) tests was conducted. The aim was to gain a greater understanding of ‘real-life’ community based clinical management of liver disease. <h3>Methods</h3> The audit consisted of a retrospective SYSTM 1 database search (2009 – 2011) for patients with an ALT ≥70, from 6 GP practises in NHS Hull. Data from 162 patients was collected and results were analysed using the COMMANDS GP liver screen as the acceptable standard of practise, a combination of liver disease risk factors and investigations. <h3>Results</h3> Gender distribution was 111 men to 51 women; the average age was 49 years. Risk factors for liver disease were under-reported as shown below. <i>Graph 1</i> – Percentage of Patients in Primary Care with Documented Risk Factors Investigations for liver disease revealed that patients were not adequately screened. <i>Graph 2</i> – Percentage of Patients in Primary Care with Documented Investigations Only 18% of patients had a documented diagnosis. GPs gave a diagnosis in 11% of cases and 7% were referred to a specialist. <i>Graph 3</i> – Referral Pattern for Patients with a Documented Diagnosis We collected up to 10 retrospective abnormal ALT results per patient working back from the data collection date. In total, we recorded 562 abnormal ALT results. <i>Graph 4</i> – Distribution of ALT Results in Audit Patients GP actions taken to manage the abnormal ALT results above, as defined by SYSTM1 drop down boxes, were reviewed. The audit found that ALT results were often incorrectly assessed by GPs according to standard laboratory parameters. <i>Graph 5</i> – GP and Audit Labelling of ALT Results <h3>Conclusion</h3> This audit showed that there is a lack of consistency in how GPs make clinical decisions. There is no clearly defined standard practise for investigating abnormal LFTs in primary care. More work on management guidelines that are easy and practical is required. <h3>Disclosure of Interest</h3> None Declared
Newly discovered coronavirus as the primary cause of severe acute respiratory syndrome
Authors: Thijs Kuiken, Ron AM Fouchier, Martin Schutten, Guus F Rimmelzwaan, Geert van Amerongen, Debby van Riel, Jon D Laman, Ton de Jong, Gerard van Doornum, Wilina Lim, Ai Ee Ling, Paul KS Chan, John S Tam, Maria C Zambon, Robin Gopal, Christian Drosten, Sylvie van der Werf, Nicolas Escriou, Jean-Claude Manuguerra, Klaus Stöhr, J S Malik Peiris, Albert DME Osterhaus
Journal: The Lancet (2003)
Evolving Treatment Strategies for Inflammatory Bowel Disease
Authors: Stephen B. Hanauer, Themistocles Dassopoulos
Journal: Annual Review of Medicine (2001)

Crohn's disease and ulcerative colitis are idiopathic inflammatory bowel diseases characterized by dysregulated intestinal immune responses in genetically susceptible hosts. Conventional approaches to the medical therapy of ulcerative colitis and Crohn's disease can now be directed at either induction or maintenance of remission to improve therapeutic efficacy while minimizing complications. Newer approaches have expanded the utility of conventional therapies by improving both safety and efficacy and highlight the importance of specific targets along the immunoinflammatory pathways. The combination of conventional and novel approaches now offers the potential of modifying the natural history of these diseases.
The human milk oligosaccharide disialyllacto-N-tetraose prevents necrotising enterocolitis in neonatal rats
Authors: Evelyn Jantscher-Krenn, Monica Zherebtsov, Caroline Nissan, Kerstin Goth, Yigit S Guner, Natasha Naidu, Biswa Choudhury, Anatoly V Grishin, Henri R Ford, Lars Bode
Journal: Gut (2011)

Background Necrotising enterocolitis (NEC) is one of the most common and fatal intestinal disorders in preterm infants. Breast-fed infants are at lower risk for NEC than formula-fed infants, but the protective components in human milk have not been identified. In contrast to formula, human milk contains high amounts of complex glycans. Objective To test the hypothesis that human milk oligosaccharides (HMO) contribute to the protection from NEC. Methods Since human intervention studies are unfeasible due to limited availability of HMO, a neonatal rat NEC model was used. Pups were orally gavaged with formula without and with HMO and exposed to hypoxia episodes. Ileum sections were scored blindly for signs of NEC. Two-dimensional chromatography was used to determine the most effective HMO, and sequential exoglycosidase digestions and linkage analysis was used to determine its structure. Results Compared to formula alone, pooled HMO significantly improved 96-hour survival from 73.1% to 95.0% and reduced pathology scores from 1.98±1.11 to 0.44±0.30 (p<0.001). Within the pooled HMO, a specific isomer of disialyllacto-N-tetraose (DSLNT) was identified to be protective. Galacto-oligosaccharides, currently added to formula to mimic some of the effects of HMO, had no effect. Conclusion HMO reduce NEC in neonatal rats and the effects are highly structure specific. If these results translate to NEC in humans, DSLNT could be used to prevent or treat NEC in formula-fed infants, and its concentration in the mother's milk could serve as a biomarker to identify breast-fed infants at risk of developing this disorder.
Liver fibrosis is not associated with steatosis but with necroinflammation in French patients with chronic hepatitis C
Authors: T Asselah
Journal: Gut (2003)

<b>Background:</b> In chronic hepatitis C, it has been suggested that steatosis could accelerate progression of fibrosis. However, results of the few published studies are controversial. <b>Aim:</b> To determine the characteristics (epidemiological, biological, and histological) associated with steatosis and its relationship with liver lesions (grade of necroinflammation and stage of fibrosis) in patients with chronic hepatitis C. <b>Methods:</b> From November 2000 to July 2001, untreated consecutive adults with chronic hepatitis C admitted for liver biopsy were included in this study. On the day of liver biopsy, a questionnaire for risk factors was completed prospectively, and a blood sample was obtained for laboratory analysis. <b>Results:</b> Our study included 290 patients (143 men, 147 women). Mean body mass index (BMI) was 24 (3.8) kg/m<sup>2</sup>. Proportions of patients with genotypes 1 and 3 were, respectively, 48% and 18%. A total of 135 patients (46.6%) had steatosis. Liver steatosis, in multivariate analysis, was associated with hepatitis C virus genotype 3, higher grade of necroinflammation, and higher BMI. There was no significant association between stage of fibrosis and liver steatosis. In multivariate analysis, high stage of fibrosis was associated with male sex, age over 50 years, high BMI, and high grade of necroinflammation. <b>Conclusion:</b> In our population of patients with chronic hepatitis C, steatosis does not seem to be an important determinant of liver fibrosis. High grade of necroinflammation is associated with a high stage of fibrosis.
The Editor, 'The British Journal of Dermatology'. Ultralanum v. Betnovate
Authors: James Coburn, Benjamin Portnoy
Journal: British Journal of Dermatology (1967)

Journal Article The Editor, ‘The British Journal of Dermatology’. Ultralanum v. Betnovate Get access James Coburn, James Coburn Manchester and Salford Hospital for Skin Diseases, Quay St., Manchester Search for other works by this author on: Oxford Academic Google Scholar Benjamin Portnoy Benjamin Portnoy Manchester and Salford Hospital for Skin Diseases, Quay St., Manchester Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 79, Issue 12, 1 December 1967, Pages 728–729, https://doi.org/10.1111/j.1365-2133.1967.tb11454.x Published: 01 December 1967
Dietary N-3 polyunsaturated fatty acids decrease biliary cholesterol saturation in gallstone disease
Authors: Frieder Berr, Joseph Holl, Dieter Jüngst, Sven Fischer, Werner O. Richter, Bernd Seifferth, Gustav Paumgartner
Journal: Hepatology (1992)

Because fatty acid composition of biliary phospholipids influences cholesterol secretion into bile, we investigated whether replacement of n-1 monounsaturated or n-6 polyunsaturated fatty acids with n-3 polyunsaturated fatty acids in biliary phosphatidylcholines reduces supersaturation with cholesterol and prevents precipitation of cholesterol crystals in bile of gallstone patients. Seven patients with radiolucent gallstones in functioning gallbladders were studied before (control) and after 5 wk of dietary supplementation with marine fish oil (11.3 gm/day = 3.75 gm n-3 polyunsaturated fatty acids/day). Duodenal bile was collected for analysis during intravenous infusion of cholecystokinin. Gallbladder emptying in response to cholecystokinin was comparable before and during intake of n-3 polyunsaturated fatty acids. Intake of n-3 polyunsaturated fatty acids increased (p < 0.001) the fractions of eicosapentaenoic and docosahexaenoic acids and decreased the fractions of linoleic (p < 0.001) and arachidonic acids (p < 0.02) in biliary phospholipids. Concomitantly, the molar ratio of cholesterol to phospholipids decreased (−19%; p < 0.05). As a consequence, the cholesterol saturation index was reduced by −25% (p = 0.01), from 1.60 ± 0.44 to 1.24 ± 0.38. However, in vitro nucleation time of duodenal bile was not prolonged. The decrease in cholesterol saturation was not sufficient to prevent nucleation of cholesterol crystals in bile of gallstone patients. In conclusion, our data suggest that cholesterol saturation can be influenced by the fatty acid composition of the phosphatidylcholines secreted in bile. (HEPATOLOGY 1992;16:960–967.)
Inherited human OX40 deficiency underlying classic Kaposi sarcoma of childhood
Authors: Minji Byun, Cindy S. Ma, Arzu Akçay, Vincent Pedergnana, Umaimainthan Palendira, Jinjong Myoung, Danielle T. Avery, Yifang Liu, Avinash Abhyankar, Lazaro Lorenzo, Monika Schmidt, Hye Kyung Lim, Olivier Cassar, Melanie Migaud, Flore Rozenberg, Nur Canpolat, Gönül Aydoğan, Bernhard Fleckenstein, Jacinta Bustamante, Capucine Picard, Antoine Gessain, Emmanuelle Jouanguy, Ethel Cesarman, Martin Olivier, Philippe Gros, Laurent Abel, Michael Croft, Stuart G. Tangye, Jean-Laurent Casanova
Journal: The Journal of Experimental Medicine (2013)

Kaposi sarcoma (KS), a human herpes virus 8 (HHV-8; also called KSHV)–induced endothelial tumor, develops only in a small fraction of individuals infected with HHV-8. We hypothesized that inborn errors of immunity to HHV-8 might underlie the exceedingly rare development of classic KS in childhood. We report here autosomal recessive OX40 deficiency in an otherwise healthy adult with childhood-onset classic KS. OX40 is a co-stimulatory receptor expressed on activated T cells. Its ligand, OX40L, is expressed on various cell types, including endothelial cells. We found OX40L was abundantly expressed in KS lesions. The mutant OX40 protein was poorly expressed on the cell surface and failed to bind OX40L, resulting in complete functional OX40 deficiency. The patient had a low proportion of effector memory CD4+ T cells in the peripheral blood, consistent with impaired CD4+ T cell responses to recall antigens in vitro. The proportion of effector memory CD8+ T cells was less diminished. The proportion of circulating memory B cells was low, but the antibody response in vivo was intact, including the response to a vaccine boost. Together, these findings suggest that human OX40 is necessary for robust CD4+ T cell memory and confers apparently selective protective immunity against HHV-8 infection in endothelial cells.
CCR5 Expression Influences the Progression of Human Breast Cancer in a p53-dependent Manner
Authors: Santos Mañes, Emilia Mira, Ramón Colomer, Sagrario Montero, Luis M. Real, Concepción Gómez-Moutón, Sonia Jiménez-Baranda, Alfredo Garzón, Rosa Ana Lacalle, Keith Harshman, Agustín Ruíz, Carlos Martínez-A.
Journal: The Journal of Experimental Medicine (2003)

Chemokines are implicated in tumor pathogenesis, although it is unclear whether they affect human cancer progression positively or negatively. We found that activation of the chemokine receptor CCR5 regulates p53 transcriptional activity in breast cancer cells through pertussis toxin-, JAK2-, and p38 mitogen-activated protein kinase-dependent mechanisms. CCR5 blockade significantly enhanced proliferation of xenografts from tumor cells bearing wild-type p53, but did not affect proliferation of tumor xenografts bearing a p53 mutation. In parallel, data obtained in a primary breast cancer clinical series showed that disease-free survival was shorter in individuals bearing the CCR5Delta32 allele than in CCR5 wild-type patients, but only for those whose tumors expressed wild-type p53. These findings suggest that CCR5 activity influences human breast cancer progression in a p53-dependent manner.
A Conditionally Immortalized Human Podocyte Cell Line Demonstrating Nephrin and Podocin Expression
Authors: Moin A. Saleem, Michael J. O’Hare, Jochen Reiser, Richard J. Coward, Carol D. Inward, Timothy Farren, Chang Ying Xing, Lan Ni, Peter W. Mathieson, Peter Mundel
Journal: Journal of the American Society of Nephrology (2002)

Recent molecular insights have established the podocyte as a key component of the glomerular filtration barrier, and hence an important common pathway in proteinuric diseases. A conditionally immortalized human podocyte cell line has been developed by transfection with the temperature-sensitive SV40-T gene. These cells proliferate at the "permissive" temperature (33 degrees C). After transfer to the "nonpermissive" temperature (37 degrees C), they entered growth arrest and expressed markers of differentiated in vivo podocytes, including the novel podocyte proteins, nephrin, podocin, CD2AP, and synaptopodin, and known molecules of the slit diaphragm ZO-1, alpha-, beta-, and gamma-catenin and P-cadherin. The differentiation was accompanied by a growth arrest and the upregulation of cyclin-dependent kinase inhibitors, p27 and p57, as well as cyclin D(1), whereas cyclin A was downregulated. These data are consistent with cell cycle protein expression during podocyte maturation in vivo. In conclusion, the development of this cell line provides a new tool in the study of podocyte biology, which will enable accurate assessment of the behavior of these complex cells in health and disease.
Sexual Counseling for Individuals With Cardiovascular Disease and Their Partners
Authors: Elaine E. Steinke, Tiny Jaarsma, Susan A. Barnason, Molly Byrne, Sally Doherty, Cynthia M. Dougherty, Bengt Fridlund, Donald D. Kautz, Jan Mårtensson, Victoria Mosack, Debra K. Moser
Journal: Circulation (2013)

6][47][48][49] Assumptions, stereotypical views, and overprotective judgments on the part of the healthcare professional may unnecessarily deter sexual counseling.
Systemic factors are trophic in bypassed rat small intestine in the absence of luminal contents.
Authors: V Albert, G P Young, C L Morton, P Robinson, P S Bhathal
Journal: Gut (1990)

Mucosal histology, crypt cell proliferation and brush border enzymes were measured in rats with varying degrees of jejunoileal bypass, in order to compare the effect of systemic and luminal factors on adaptive growth and differentiation (brush border enzymes) in small intestinal epithelium. Eighty five percent jejunoileal bypass caused a functional short gut; in intestine remaining in continuity there were significant increases in segmental weight, villus area and crypt depth, compared with sham operated controls and 25% jejunoileal bypass rats. Despite villus cell hyperplasia in 85% bypass rats, mucosal sucrase and alkaline phosphatase fell in jejunum and remained low in ileum, while leucine amino peptidase rose in ileum. There was a significant fall in villus area (p less than 0.01) and crypt cell production (p less than 0.001) in self emptying loops of 25% bypass rats not exposed to luminal contents compared with control segments of sham operated rats. In contrast, self emptying loops of 85% bypass rats were not atrophied despite the much greater distance from luminal nutrients; the villus area (p less than 0.01) and crypt cell production (p less than 0.005) were higher than in 25% bypass rats, and at least as great as in sham operated rats. These results indicate that adaptive hyperplasia has a variable effect on expression of brush border enzymes which might reflect villus cell immaturity. The atrophic effect of diversion of luminal contents can be counteracted by systemic growth factors released as part of the adaptive response; thus systemic growth factors are not dependent on a permissive effect of luminal contents.
Apoptosis in cardiac diseases: stress- and mitogen-activated signaling pathways
Authors: G Feuerstein
Journal: Cardiovascular Research (2000)

Apoptosis is a form of cell death that involves discrete genetic and molecular programs, de novo protein expression and a unique cellular phenotype. Evidence for the existence of apoptosis in the human heart has been reported in various cardiac diseases, including ischemic and non-ischemic heart failure, myocardial infarction and arrhythmias. Among the most potent stimuli that elicit cardiomyocyte apoptosis are: oxygen radicals (including NO), cytokines (FAS/TNFα-receptor signaling), stress conditions (chemical or physical, e.g., radiation), sphingolipid metabolites (ceramide) and autocoids, e.g., angiotensin II. Apoptosis of cardiac myocytes may contribute to progressive pump-failure, arrhythmias and cardiac remodeling. The recognition of numerous molecular targets associated with cardiomyocyte apoptosis may provide novel therapeutic strategies for diverse cardiac ailments, as recently suggested by pharmacologic studies in experimental animals. This review paper is aimed to highlight the role of protein kinase signaling pathways in apoptosis with special attention to the stress-activated protein kinases (SAPK) and mitogen-activated protein kinases (MAPK) systems.
Activation of Forkhead Box O Transcription Factors by Oncogenic BRAF Promotes p21cip1-Dependent Senescence
Authors: Peter L.J. de Keizer, Leisl M. Packer, Anna A. Szypowska, Paulien E. Riedl-Polderman, Niels J.F. van den Broek, Alain de Bruin, Tobias B. Dansen, Richard Marais, Arjan B. Brenkman, Boudewijn M.T. Burgering
Journal: Cancer Research (2010)

Oncogene-induced senescence (OIS) is a potent tumor-suppressive mechanism that is thought to come at the cost of aging. The Forkhead box O (FOXO) transcription factors are regulators of life span and tumor suppression. However, whether and how FOXOs function in OIS have been unclear. Here, we show a role for FOXO4 in mediating senescence by the human BRAF(V600E) oncogene, which arises commonly in melanoma. BRAF(V600E) signaling through mitogen-activated protein kinase/extracellular signal-regulated kinase kinase resulted in increased reactive oxygen species levels and c-Jun NH(2) terminal kinase-mediated activation of FOXO4 via its phosphorylation on Thr(223), Ser(226), Thr(447), and Thr(451). BRAF(V600E)-induced FOXO4 phosphorylation resulted in p21(cip1)-mediated cell senescence independent of p16(ink4a) or p27(kip1). Importantly, melanocyte-specific activation of BRAF(V600E) in vivo resulted in the formation of skin nevi expressing Thr(223)/Ser(226)-phosphorylated FOXO4 and elevated p21(cip1). Together, these findings support a model in which FOXOs mediate a trade-off between cancer and aging.
Specific Wiring of Distinct Amacrine Cells in the Directionally Selective Retinal Circuit Permits Independent Coding of Direction and Size
Authors: Alex Hoggarth, Amanda J. McLaughlin, Kara Ronellenfitch, Stuart Trenholm, Rishi Vasandani, Santhosh Sethuramanujam, David Schwab, Kevin L. Briggman, Gautam B. Awatramani
Journal: Neuron (2015)
Structure–Function Relationship of Cytokine Induction by Lipoteichoic Acid from<i>Staphylococcus aureus</i>
Authors: Siegfried Morath, Armin Geyer, Thomas Hartung
Journal: The Journal of Experimental Medicine (2001)

Lipoteichoic acids (LTAs) have been proposed as putative Gram-positive immunostimulatory counterparts to Gram-negative lipopolysaccharides. However, LTA from Staphylococcus aureus, the clinically most frequent Gram-positive pathogen, was inactive after purification. Here, a novel isolation procedure to prepare pure (>99%) biologically active LTA, allowing the first structural analysis by nuclear magnetic resonance and mass spectrometry, is described. A comparison with LTA purified by standard techniques revealed that alanine substituents are lost during standard purification, resulting in attenuated cytokine induction activity. In line with this finding, hydrolysis of alanine substituents of active LTA decimated cytokine induction. LTA represents a major immunostimulatory component of S. aureus.
Who should get a liver graft?
Authors: Richard B. Freeman, Neville Jamieson, Douglas E. Schaubel, Robert J. Porte, Federico G. Villamil
Journal: Journal of Hepatology (2009)

Determining who should get one of the extremely scarce deceased donor liver grafts is becoming an increasingly complex and difficult problem. In the early stages of the liver transplantation field, centers became aware of potential donors, decided whether to accept this donation, and chose which candidate should receive the graft without much consideration for the other centers and patients outside of their own area. However, with the increasing success of liver transplantation, maturation of the hepatitis C virus (HCV) epidemic, and broadening of the indications for liver transplantation to malignancies such as hepatocellular cancer and other previously contraindicated diagnoses, the demand for liver grafts has far outpaced the supply.