tbuckley/cabot-search huggingface dataset:
The acute respiratory distress syndrome: fibrosis in the fast lane
Authors: R. MARSHALL, G. BELLINGAN, G. LAURENT
Journal: Thorax (1998)

<b>Background:</b> Epidemiological research in the field of soft tissue neck and upper limb disorders has been hampered by the lack of an agreed system of diagnostic classification. In 1997, a United Kingdom workshop agreed consensus definitions for nine of these conditions. From these criteria, an examination schedule was developed and validated in a hospital setting. <b>Objective:</b> To investigate the reliability of this schedule in the general population. <b>Methods:</b> Ninety seven adults of working age reporting recent neck or upper limb symptoms were invited to attend for clinical examination consisting of inspection and palpation of the upper limbs, measurement of active and passive ranges of motion, and clinical provocation tests. A doctor and a trained research nurse examined each patient separately, in random order and blinded to each other9s findings. <b>Results:</b> Between observer repeatability of the schedule was generally good, with a median κ coefficient of 0.66 (range 0.21 to 0.93) for each of the specific diagnoses considered. <b>Conclusion:</b> As expected, the repeatability of tests is poorer in the general population than in the hospital clinic, but the Southampton examination schedule is sufficiently reproducible for epidemiological research in the general population.
Stem cell bill may be stalled in US Senate
Authors: Janice Hopkins Tanne
Journal: BMJ (2005)

Action on the bill to increase funding for embryonic stem cell research and to expand the number of embryonic stem cell lines available seemed to have stalled with only days left before the US Senate began its August vacation. The House of Representatives passed the bill in May challenging George Bush, who has limited federal funding to the 22 stem cell lines in existence on 9 August 2001. Scientists say that few of these lines remain and that all may be contaminated ( BMJ 2005;330:214).

The bill, passed by the House of Representatives and awaiting a Senate vote before, normally, being signed into law by the president, would fund research on thousands of frozen embryos left over after fertility treatment and voluntarily donated by the couples ( BMJ 2005;330:1285).

President Bush has said that he would …
Diabetes in American Indians of Washington, Oregon, and Idaho
Authors: William L Freeman, Gwendolyn M Hosey, Paula Diehr, Dorothy Gohdes
Journal: Diabetes Care (1989)

The prevalence of diabetes among 29,000 American Indians living on or near 10 reservations in the Pacific Northwest was established from clinical data sources. The age- and sex-adjusted prevalence rate in 1987 was three times higher [95% confidence interval (CI) 2.8-3.1] than the comparable United States rate in 1980. The age-adjusted prevalence for women was 1.3 times that for men (95% CI 1.2-1.4). The prevalence varied by culture area. Reservation communities whose principal tribe came from the Great Basin culture area had 3.6 times more diabetes than found in the U.S. as a whole. Reservation communities whose principal tribe was from the Plateau culture had 3.0 times more diabetes than found in the U.S., and those from the Northwest Coast culture had 1.9 times more diabetes than found in the U.S. The reasons for these variations are unknown and warrant investigation.
Why we should allow performance enhancing drugs in sport
Authors: J Savulescu, B Foddy, M Clayton
Journal: British Journal of Sports Medicine (2004)

The legalisation of drugs in sport may be fairer and safer

In 490 BC, the Persian Army landed on the plain of Marathon, 25 miles from Athens. The Athenians sent a messenger named Feidipides to Sparta to ask for help. He ran the 150 miles in two days. The Spartans were late. The Athenians attacked and, although outnumbered five to one, were victorious. Feidipides was sent to run back to Athens to report victory. On arrival, he screamed “We won” and dropped dead from exhaustion.

The marathon was run in the first modern Olympics in 1896, and in many ways the athletic ideal of modern athletes is inspired by the myth of the marathon. Their ideal is superhuman performance, at any cost.

The use of performance enhancing drugs in the modern Olympics is on record as early as the games of the third Olympiad, when Thomas Hicks won the marathon after receiving an injection of strychnine in the middle of the race.1 The first official ban on “stimulating substances” by a sporting organisation was introduced by the International Amateur Athletic Federation in 1928.2

Using drugs to cheat in sport is not new, but it is becoming more effective. In 1976, the East German swimming team won 11 out of 13 Olympic events, and later sued the government for giving them anabolic steroids.3 Yet despite the health risks, and despite the regulating bodies’ attempts to eliminate drugs from sport, the use of illegal substances is widely known to be rife. It hardly raises an eyebrow now when some famous athlete fails a dope test.

In 1992, Vicky Rabinowicz interviewed small groups of athletes. She found that Olympic athletes, in general, believed that most successful athletes were using banned substances.4

Much of the writing on the use of …
Managing and preventing depression in adolescents
Authors: A. Thapar, S. Collishaw, R. Potter, A. K Thapar
Journal: BMJ (2010)

#### Summary points 

Depressive disorder affects 1-6% of adolescents each year worldwide,1 2 and early onset heralds a more severe and persistent illness in adult life.3 Effective treatment is available, but best treatment practice is controversial because of concerns about the use of antidepressants in young people and inconsistencies in evidence. This review provides guidance for non-specialists on the assessment and management of adolescent unipolar depression and considers emerging evidence on prevention strategies.

#### Sources and selection criteria

We searched for papers published between 1990 and 2009 using key index terms (adolescent depression, treatment, and prevention) on PubMed (Medline and life science journals). In addition, we consulted the Institute of Medicine report “Preventing mental, emotional and behavioral disorders among young people: progress and possibilities” (published by National Academies Press 2009), NICE guidelines on adolescent depression, Cochrane systematic reviews, and BMJ Clinical Evidence . This was supplemented by reviews and our own knowledge.

Evidence from prospective community studies suggests that rates of underdiagnosis and undertreatment of depression are higher in adolescents than in adults.4 Large scale, longitudinal population based and clinical cohort studies have consistently shown that rates of depression rise sharply after puberty, especially in girls, with immediate and long term risks.5 6 Clinical depression …
Doctors criticise new advertising rules that allow celebrities to endorse e-cigarettes
Authors: A. O'Dowd
Journal: BMJ (2014)

New rules to govern the advertising of electronic (e) cigarettes will not allow companies to target under 18s and will state that advertisements must not promote the use of tobacco products. 

However, doctors’ leaders and experts have criticised a decision allowing celebrity endorsements and free samples to be given, which they say could undermine efforts to quit smoking. Also, companies will be allowed to advertise e-cigarettes on television and actually show the devices, which they have not been able to do previously.

The Committee of Advertising Practice, which writes and maintains the …
Somatic Mutations and Deletions of the E-Cadherin Gene Predict Poor Survival of Patients With Gastric Cancer
Authors: Giovanni Corso, Joana Carvalho, Daniele Marrelli, Carla Vindigni, Beatriz Carvalho, Raquel Seruca, Franco Roviello, Carla Oliveira
Journal: Journal of Clinical Oncology (2013)

Purpose The prognosis of gastric cancer (GC) is poor, and the molecular pathogenesis players are vastly unknown. Surgery remains the primary option in GC treatment. The aim of this study was to investigate the impact of somatic CDH1 alterations in prognosis and survival of patients with GC. Patients and Methods A series of patients with sporadic and familial GC (diffuse and intestinal; n = 246) were analyzed for somatic CDH1 mutations, promoter hypermethylation, and loss of heterozygosity (LOH) by polymerase chain reaction sequencing. E-cadherin protein expression was determined by immunohistochemistry. Associations between molecular, clinicopathologic, and survival data were analyzed. Results CDH1 somatic alterations were found in approximately 30% of all patients with GC. Both histologic types of sporadic GC displayed LOH in 7.5%, mutations in 1.7%, and hypermethylation in 18.4% of patients. Primary tumors from hereditary diffuse GC, lacking germline CDH1 alterations, showed exclusively CDH1 promoter hypermethylation in 50% of patients. Familial intestinal GC (FIGC) tumors showed LOH in 9.4% and hypermethylation in 17.0%. CDH1 alterations did not associate with a particular pattern of E-cadherin expression. Importantly, the worst patient survival rate among all GCs analyzed was seen in patients with tumors carrying CDH1 structural alterations, preferentially those belonging to FIGC families. Conclusion CDH1 somatic alterations exist in all clinical settings and histotypes of GC and associate with different survival rates. Their screening at GC diagnosis may predict patient prognosis and is likely to improve management of patients with this disease.
Alcohol Intake and Blood Pressure: A Systematic Review Implementing a Mendelian Randomization Approach
Authors: Lina Chen, George Davey Smith, Roger M Harbord, Sarah J Lewis
Journal: PLoS Medicine (2008)

Alcohol has been reported to be a common and modifiable risk factor for hypertension. However, observational studies are subject to confounding by other behavioural and sociodemographic factors, while clinical trials are difficult to implement and have limited follow-up time. Mendelian randomization can provide robust evidence on the nature of this association by use of a common polymorphism in aldehyde dehydrogenase 2 (ALDH2) as a surrogate for measuring alcohol consumption. ALDH2 encodes a major enzyme involved in alcohol metabolism. Individuals homozygous for the null variant (*2*2) experience adverse symptoms when drinking alcohol and consequently drink considerably less alcohol than wild-type homozygotes (*1*1) or heterozygotes. We hypothesise that this polymorphism may influence the risk of hypertension by affecting alcohol drinking behaviour.We carried out fixed effect meta-analyses of the ALDH2 genotype with blood pressure (five studies, n = 7,658) and hypertension (three studies, n = 4,219) using studies identified via systematic review. In males, we obtained an overall odds ratio of 2.42 (95% confidence interval [CI] 1.66-3.55, p = 4.8 x 10(-6)) for hypertension comparing *1*1 with *2*2 homozygotes and an odds ratio of 1.72 (95% CI 1.17-2.52, p = 0.006) comparing heterozygotes (surrogate for moderate drinkers) with *2*2 homozygotes. Systolic blood pressure was 7.44 mmHg (95% CI 5.39-9.49, p = 1.1 x 10(-12)) greater among *1*1 than among *2*2 homozygotes, and 4.24 mmHg (95% CI 2.18-6.31, p = 0.00005) greater among heterozygotes than among *2*2 homozygotes.These findings support the hypothesis that alcohol intake has a marked effect on blood pressure and the risk of hypertension.
Quantitative and qualitative comparison of gall bladder mucus glycoprotein from patients with and without gall stones.
Authors: P R Harvey, C A Rupar, S Gallinger, C N Petrunka, S M Strasberg
Journal: Gut (1986)

Human gall bladder mucus glycoprotein was isolated by Sepharose 4B gel filtration followed by caesium chloride density gradient ultracentrifugation from four groups: patients with cholesterol gall stones, patients with pigmented stones, patients with complete obstruction of the cystic duct and patients with no biliary tract abnormalities (controls). Mucus glycoprotein concentrations in cholesterol gall stone bile (203 micrograms/ml +/- 199 SD, n = 17), pigment gall stone bile (110 micrograms/ml +/- 77 SD, n = 6) and control gall bladder bile (96 micrograms/ml +/- 98 SD, n = 11) were not significantly different. While bile from patients with complete obstruction of the cystic duct contained significantly higher concentrations of mucus glycoprotein (6220 micrograms/ml +/- 4130, n = 4). In vitro cholesterol nucleation time was not correlated to gall bladder mucus glycoprotein concentrations. Qualitative analysis of the carbohydrate and amino acid composition showed a basic structure typical of mucus glycoproteins in general. It is unlikely that either quantitative or qualitative differences in mucus glycoproteins are responsible for the rapid in vitro nucleation time characteristic of cholesterol gall stone patients.
Proteomic patterns of tumour subsets in non-small-cell lung cancer
Authors: Kiyoshi Yanagisawa, Yu Shyr, Baogang J Xu, Pierre P Massion, Paul H Larsen, Bill C White, John R Roberts, Mary Edgerton, Adriana Gonzalez, Sorena Nadaf, Jason H Moore, Richard M Caprioli, David P Carbone
Journal: The Lancet (2003)
Transforming Growth Factor-β Induces Renal Epithelial Jagged-1 Expression in Fibrotic Disease
Authors: Jeremiah Morrissey, Guangjie Guo, Kazuaki Moridaira, Melanie Fitzgerald, Ruth McCracken, Timothy Tolley, Saulo Klahr
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. For elucidation of the mechanisms by which growth factors and cytokines affect renal epithelial cells, gene array analysis of renal cells cultured in the presence of transforming growth factor-β1 (TGF-β1) was performed. Many genes that were not previously considered to be involved in renal cell biologic processes were affected, one of which was jagged-1. The jagged ligand/notch receptor family controls the formation of boundaries between groups of cells and regulates cell fates. On the basis of the array analysis, jagged-1 expression was further evaluated in cultured cells and in C57BL/6 mice with a model of unilateral ureteral obstruction (UUO). Recombinant human TGF-β1 increased jagged-1 mRNA levels at concentrations between 10−11 and 10−10 M. There was a commensurate increase in jagged-1 protein levels, as assessed by Western blotting. The expression of jagged-1 mRNA and protein was observed to be significantly increased in the kidneys of C57BL/6 mice with obstructed ureters, compared with the contralateral kidneys, at 7 and 14 d of UUO. Immunohistochemical analyses demonstrated jagged-1 expression in distal tubules of kidneys from normal mice or contralateral kidneys from mice with UUO. Jagged-1 protein expression was increased in tubules not yet in apparent atrophy in the kidneys with an obstructed ureter. Jagged-1 expression was significantly increased in the kidneys of normal mice treated with TGF-β1 and was decreased in the kidneys of mice with UUO treated with a TGF-β receptor II-Fc chimera. These results suggest that jagged-1 is expressed in normal kidneys and that this expression is upregulated during renal disease, in a TGF-β-dependent manner.
Identification of a Tumor-Suppressive Human-Specific MicroRNA within the<i>FHIT</i>Tumor-Suppressor Gene
Authors: Baocheng Hu, Xiaomin Ying, Jian Wang, Jittima Piriyapongsa, I. King Jordan, Jipo Sheng, Fang Yu, Po Zhao, Yazhuo Li, Hongyan Wang, Wooi Loon Ng, Shuofeng Hu, Xiang Wang, Chenguang Wang, Xiaofei Zheng, Wuju Li, Walter J. Curran, Ya Wang
Journal: Cancer Research (2014)

Abstract Loss or attenuated expression of the tumor-suppressor gene FHIT is associated paradoxically with poor progression of human tumors. Fhit promotes apoptosis and regulates reactive oxygen species; however, the mechanism by which Fhit inhibits tumor growth in animals remains unclear. In this study, we used a multidisciplinary approach based on bioinformatics, small RNA library screening, human tissue analysis, and a xenograft mouse model to identify a novel member of the miR-548 family in the fourth intron of the human FHIT gene. Characterization of this human-specific microRNA illustrates the importance of this class of microRNAs in tumor suppression and may influence interpretation of Fhit action in human cancer. Cancer Res; 74(8); 2283–94. ©2014 AACR.
MAINTENANCE OF POTASSIUM EXCRETION DESPITE REDUCTION OF GLOMERULAR FILTRATION DURING SODIUM DIURESIS
Authors: Douglas G. Davidson, Norman G. Levinsky, Robert W. Berliner
Journal: Journal of Clinical Investigation (1958)

It has been clearly established that mammalian renal tubules can secrete potassium. However, it has not been shown in mammals under physiologic conditions what proportion of the urinary potassium is derived from the filtered potassium and what proportion from secreted potassium. In experiments designed to study the various factors which influence potassium excretion it has sometimes been assumed that the reabsorption of the filtered potassium is essentially complete, and that these factors exert their effects on the secretory mechanism. However, evidence for the completeness of reabsorption of filtered potassium is limited and not conclusive. The proposed tubular mechanism for the secretion of potassium is an ion exchange process in the distal tubule (1), where cellular potassium ions are exchanged for sodium ions derived from the glomerular filtrate. It is implicit in this mechanism that potassium secretion will depend in part on the availability of sodium ions for exchange. If the proximal reabsorption of filtered potassium is complete, the rate of excretion of potassium will be independent of the filtered load of potassium, providing an adequate distal load of sodium is maintained. To test this hypothesis, the glomerular filtration rate was reduced in one kidney and the rate of excretion of potassium from this kidney was compared to that of the control kidney, during both high and low rates of sodium excretion.
Hominoid Composite Non-LTR Retrotransposons—Variety, Assembly, Evolution, and Structural Determinants of Mobilization
Authors: Bianca Ianc, Cornelia Ochis, Robert Persch, Octavian Popescu, Annette Damert
Journal: Molecular Biology and Evolution (2014)

SVA (SINE-R-VNTR-Alu) elements constitute the youngest family of composite non-LTR retrotransposons in hominoid primates. The sequence of their assembly, however, remains unclear. Recently, a second family of VNTR-containing composites, LAVA (L1-Alu-VNTR-Alu), has been identified in gibbons. We now report the existence of two additional VNTR composite families, PVA (PTGR2-VNTR-Alu) and FVA (FRAM-VNTR-Alu), in the genome of Nomascus leucogenys. Like LAVA, they share the 5′-Alu-like region and VNTR with SVA, but differ at their 3′-ends. The 3′-end of PVA comprises part of the PTGR2 gene, whereas FVA is characterized by the presence of a partial FRAM element in its 3′-domain. Splicing could be identified as the mechanism of acquisition of the variant 3′-ends in all four families of VNTR composites. SVAs have been shown to be mobilized by the L1 protein machinery in trans. A critical role in this process has been ascribed to their 5′-hexameric repeat/ Alu-like region. The Alu-like region displays specific features in each of the VNTR composite families/subfamilies with characteristic deletions found in the evolutionary younger subfamilies. Using reciprocal exchanges between SVA_E and PVA/FVA elements, we demonstrate that the structure, not the presence of the (CCCTCT)n/ Alu-like region determines mobilization capacity. Combination of LAVA and SVA_E domains does not yield any active elements—suggesting the use of different combinations of host factors for the two major groups of VNTR composites. Finally, we demonstrate that the LAVA 3′-L1ME5 fragment attenuates mobilization capacity.
Entamoeba histolytica. Phagocytosis as a virulence factor.
Authors: E Orozco, G Guarneros, A Martinez-Palomo, T Sánchez
Journal: The Journal of Experimental Medicine (1983)

In this paper, we attempted to define the role of phagocytosis in the virulence of Entamoeba histolytica. We have isolated, from a highly phagocytic and virulent strain, a clone deficient in phagocytosis. Trophozoites of wild-type strain HM1:IMSS were fed with Escherichia coli strain CR34-Thy- grown on 5-bromo,2'-deoxyuridine. The trophozoites that had incorporated the base analog through phagocytosis of the bacteria were killed by irradiation with 310 nm light. The survivors, presumably trophozoites defective in phagocytosis, were grown until log phase and submitted two more times to the selection procedure. Clone L-6, isolated from a subpopulation resulting from this selection procedure, showed 75-85% less erythrophagocytic activity than the wild-type strain. The virulence of clone L-6 and strain HM1:IMSS was measured. The inoculum required to induce liver abscesses in 50% of the newborn hamsters inoculated (AD50) of HM1:IMSS was 1.5 X 10(4) trophozoites. Clone L-6 trophozoites failed to induce liver abscesses in newborn hamsters even with inocula of 5 X 10(5) trophozoites. Virulence revertants were obtained by successive passage of L-6 trophozoites through the liver of young hamsters. The trophozoites that recovered the ability to produce liver abscesses simultaneously recuperate high erythrophagocytic rates. These results show that phagocytosis is involved in the aggressive mechanisms of E. histolytica.
Complement C3 Activation Is Required for Antiphospholipid Antibody-induced Fetal Loss
Authors: V. Michael Holers, Guillermina Girardi, Lian Mo, Joel M. Guthridge, Hector Molina, Silvia S. Pierangeli, Ricardo Espinola, Liu E. Xiaowei, Dailing Mao, Christopher G. Vialpando, Jane E. Salmon
Journal: The Journal of Experimental Medicine (2002)

The antiphospholipid syndrome (APS) is characterized by recurrent fetal loss, vascular thrombosis, and thrombocytopenia occurring in the presence of antiphospholipid (aPL) antibodies. The pathogenesis of fetal loss and tissue injury in APS is incompletely understood, but is thought to involve platelet and endothelial cell activation as well as procoagulant effects of aPL antibodies acting directly on clotting pathway components. Recent studies have shown that uncontrolled complement activation in the placenta leads to fetal death in utero. We hypothesized that aPL antibodies activate complement in the placenta, generating split products that mediate placental injury and lead to fetal loss and growth retardation. To test this hypothesis, we used a murine model of APS in which pregnant mice are injected with human IgG containing aPL antibodies. We found that inhibition of the complement cascade in vivo, using the C3 convertase inhibitor complement receptor 1–related gene/protein y (Crry)-Ig, blocks fetal loss and growth retardation. Furthermore, mice deficient in complement C3 were resistant to fetal injury induced by aPL antibodies. While antigenic epitopes recognized by aPL antibodies are important in the pathogenesis of APS, our data show that in vivo complement activation is required for aPL antibody-induced fetal loss and growth retardation.