tbuckley/cabot-search huggingface dataset:
Beware tobacco companies' spurious financial arguments
Authors: C. I. Vardavas, P. K. Behrakis, G. N. Connolly
Journal: BMJ (2011)

Despite the economic and health related gains of smoke-free legislation, those who oppose such legislation have suggested that it affects the revenue from the hospitality industry. Countries whose economies are under financial strain, such as Greece and Spain, are vulnerable to such pressure, …
Children with moderately elevated blood lead levels: a role for other diagnostic tests?
Authors: M E Markowitz, I Clemente, J F Rosen
Journal: Environmental Health Perspectives (1997)

In this study we examined potential limitations of relying exclusively on blood lead (BPb) levels to evaluate children with moderately elevated BPb levels (1.21-2.12 micromol/l, or 25-44 microg/dl). We tested the following hypotheses: 1) such children without elevated erythrocyte protoporphyrin (EP) levels (>=0.62 micromol/l or >/= 35 microg/dl) are unlikely to respond to a chelating agent with a brisk urinary Pb diuresis; 2) those with elevated EP levels, but low hematologic indices consistent with iron deficiency, are also unlikely to respond to a chelating agent with a robust urinary Pb diuresis; and 3) those with elevated EP levels and iron sufficiency are more likely to respond to a chelating agent. To test these hypotheses, we performed retrospective analyses of the relationships between EP concentrations, hematologic indices, and urinary Pb excretion ratios (uPbr) in moderately Pb-poisoned children undergoing the CaNa2EDTA lead mobilization test (Pb-MT). Data from 122 children were available. Urinary Pb excretion was limited in children with an EP <0.62 micromol/l (<35 microg/dl); only 5% (1/21) of Pb-MTs were positive (uPbr >=0.6). In children with an EP >=0.62 micromol/l, low hematologic indices, such as a mean corpuscular hemoglobin (MCH) <23 pg, were associated with relatively little Pb excretion (0/14 positive Pb-MTs). In contrast, 32% (28/87) of Pb-MTs were positive in children with an EP >/= 0.62 micromol/l and iron sufficiency (p<0.01 by chi-square comparison between groups with EP >/= 0.62 micromol/l and either MCH <23 pg or MCH >/= 23 pg). We conclude that only a minority of moderately Pb-poisoned children will demonstrate enhanced urinary Pb excretion in response to chelation therapy. Some of the predicted nonresponders can be readily identified by adding the EP and complete blood count to the panel of tests performed.
378 HEPATITIS B CORE (HBC) PROTEIN IS A KEY AND VERY EARLY NEGATIVE REGULATOR OF THE INTERFERON RESPONSE
Authors: M. Gruffaz, B. Testoni, S. Luangsay, M. Ait-Goughoulte, M.-A. Petit, H. Ma, K. Klumpp, H. Javanbakht, D. Durantel, F. Zoulim
Journal: Journal of Hepatology (2013)
Tuberculosis in HIV-positive patients: cellular response and immune activation in the lung.
Authors: K F Law, J Jagirdar, M D Weiden, M Bodkin, W N Rom
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

The host response to Mycobacterium tuberculosis is dependent on the accumulation and activation of cytotoxic and memory CD4+ T cells, resulting in granuloma formation and delayed type hypersensitivity. We characterized the cellular response of radiographically involved lung segments from 17 HIV-positive and 11 HIV-negative patients with acute tuberculosis (TB) using bronchoalveolar lavage (BAL) and compared the response to uninvolved segments, normal control subjects and peripheral blood. In both HIV-positive and HIV-negative patients, radiographically involved segments had significantly increased numbers of total cells per milliliter, percent of neutrophils recovered, and percent of lymphocytes recovered compared with uninvolved segments or normal control subjects, but HIV-positive patients had a lower proportion of lymphocytes in the involved segments than HIV-negative patients with tuberculosis (19 +/- 5% versus 33 +/- 5%; p < 0.05). Lymphocyte subset analysis demonstrated that HIV-positive patients had markedly reduced percentages of CD4+ lymphocytes (CD4+ lymphocytes in HIV-positive TB involved site 25 +/- 6%; HIV-negative TB involved site 73 +/- 2%; p < 0.01) and an increase in the percentage of CD8+ lymphocytes (HIV positive involved site 61 +/- 6% versus HIV negative involved site 19 +/- 3%; p < 0.01). Immunohistochemistry of lung biopsy tissue in five HIV-negative patients showed similar lymphocyte subset profiles as BAL, indicating that BAL reflects cell populations in tissue granulomas. BAL lymphocytes from four HIV-positive and four HIV-negative tuberculosis patients demonstrated immune activation by staining with a murine antibody to TIA-1, a cytoplasmic protein associated with cytotoxicity and apoptosis (HIV positive 48 +/- 6%, HIV negative 31 +/- 7%, normals 11 +/- 5%). Steady state mRNA for gamma-interferon was decreased in four HIV-positive patients when compared with four HIV-negative patients. IL-8 production was comparable in HIV-negative and HIV-positive patients with focal disease but reduced in two patients with miliary tuberculosis. We conclude that HIV-positive patients with+ tuberculosis have a reduced enrichment and activation of immune cells in the lung, and this failure of a CD4+ alveolitis limits an effective immune response.
Abstract 1564: Spanxa1 is a novel mediator of epithelial-mesenchymal transition in lung cancer
Authors: Shih-Chun Hsu, Yi-Jing Hsiao, Sing-Liang Yu, Ming-Shyue Lee
Journal: Cancer Research (2014)

Abstract SPANX (Sperm protein associated with the nucleus, X-linked) gene family express throughout spermatogenesis in agreement with a potential role in sperm development. It has been reported as a CTA (Cancer/Testis Antigen), which was highly expressed in testis and several cancers, such as gliobastoma, melanoma, testicular germ tumor and hematologic malignancies. Nevertheless, the function and molecular mechanism of SPANX involved in the cancer progression are greatly unknown. We found that the SPANX gene family member A1 (SPANXA1) was high-expressed in CL1-0, a less metastatic lung cancer cell line, and low-expressed in CL1-5, a more metastatic cell line. In vitro assays showed that the enforced expression of SPANXA1 suppressed the abilities of migration and invasion, and induced a dramatically mesenchymal - epithelial transition (EMT). In contrast, knock-down SPANXA1 could increase the cell mobility and invasiveness. To identify the underlying mechanism of SPANXA1, RNAs derived from SPANXA1-expressed cells and mock controls wrer assayed by gene expression microarrays and pathway analysis. The results showed that 1024 genes were differentially expressed in presence of SPANXA1 and six of top ten pathways belonged to EMT-related pathways analyzed by MetaCore software. The fact implied that SPANXA1 largely induces the EMT-related signalings. Quantitative RT-PCR assays were used to validate the altered expression of certain important genes induced by SPANXA1 in the identified pathways. The EMT regulating transcription factor, Slug, was decreased in SPAXA1-overexpressed cells and it also acts as a repressor for E-cadherin expression. We found that SPANXA1 mainly localized at nucleus and inhibited the formation of filopodia assayed by immunofluoresence staining. To explore the function of SPANXA1 in the nucleus, we performed Chromatin IP sequencing and the results elucidated that SPANXA1 might bind onto chromosome and regulate gene expressions. Furthermore, mouse model demonstrated that the distal metastasis was dramatically decreased in SPANXA1-overexpressed cells compared with the mock controls. These data suggest that SPANXA1 is a novel EMT modulator involved in lung cancer progression and implies the potential therapeutic role of SPANXA1 in the future. Citation Format: Shih-Chun Hsu, Yi-Jing Hsiao, Sing-Liang Yu, Ming-Shyue Lee. Spanxa1 is a novel mediator of epithelial-mesenchymal transition in lung cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1564. doi:10.1158/1538-7445.AM2014-1564
Postkala-azar dermal leishmaniasis coexisting with borderline tuberculoid leprosy
Authors: S. Bansal, A. Goel, K. Sardana, V. Kumar, N. Khurana
Journal: British Journal of Dermatology (2007)

Conflicts of interest: none declared. Sir, Postkala‐azar dermal leishmaniasis (PKDL) is a dermatosis described during the first quarter of the last century. It is a dermal manifestation in patients with treated kala‐azar, is caused by the protozoan parasite Leishmania donovani and is almost completely confined to the Indian subcontinent, particularly Eastern India, and uncommonly in certain parts of Africa. It is an unusual complication of visceral leishmaniasis (kala‐azar) characterized by erythema and induration particularly involving the butterfly area of the face, presence of hypopigmented macules that are either generalized or localized to the extremities or trunk with sparing of flexures, belt area and the midline areas, and infiltrated papules and nodules typically involving the forehead, chin and muzzle area of the face. While in Indian cases lesions of PKDL usually develop 1–5 years after treatment of kala‐azar, those in Africa may develop during or shortly after treatment. The pathogenesis of PKDL remains obscure. Histopathologically, a polymorphic infiltrate of macrophages, plasma cells and lymphocytes is seen. The detection of Leishman–Donovan (LD) bodies in the macrophages is pathognomonic. Pentavalent antimonials are the treatment of choice.
Abstract 1431: Gene expression analysis of argininosuccinate synthetase loss and the effects of pegylated arginine deiminase in malignant pleural mesothelioma
Authors: Rosalind Cutts, Puthen V. Jithesh, Barbara Delage, Phuong Luong, Gareth Thomas, Claude Chelala, Peter W. Szlosarek
Journal: Cancer Research (2014)

Abstract Malignant pleural mesothelioma (MPM) is a devastating asbestos-related malignancy that is increasing in many countries worldwide with few systemic treatment options beyond platinum and antifolate chemotherapy. Deficiency of the arginine biosynthetic enzyme argininosuccinate synthetase (ASS1) occurs in up to 50% of MPM cell lines and primary tumors and is being validated as a biomarker in patients treated with the arginine-depleting agent, pegylated arginine deiminase (ADI-PEG20). To understand the role of ASS1 loss and the effect of the ADI-PEG20 in MPM we used pathway analysis tools on microarray gene expression data from a representative panel of MPM cell lines. First, we identified that ASS1 loss was linked to several protumorigenic functions including increased cell invasiveness and migration, which were confirmed subsequently using invasion assays and organotypic modelling, respectively. We also detected a large number of enriched pathways connected to the immune response including communication between innate and adaptive immune cells and interferon signalling. Furthermore, ASS1 deficiency was linked to worse outcome with a median survival of 6 months in ASS1 low expressors compared to 12 months for ASS1 high expressors using a retrospective dataset (n=41; p=0.003). Second, ADI-PEG20 treatment modulated numerous pathways in ASS1-deficient cells including suppression of mTOR and folate metabolism, while promoting stress, oxidant and amino acid signalling. Third, bioinformatics analyses of drug interactions using Connectivity map revealed that arginine deprivation using ADI-PEG20 may potentiate several chemotherapeutic and targeted agents in the clinic. Taken together, our bioinformatics approach links loss of ASS1 in MPM cells to a more aggressive phenotype and identifies several potential combination strategies with ADI-PEG20 for further clinical investigation. Citation Format: Rosalind Cutts, Puthen V. Jithesh, Barbara Delage, Phuong Luong, Gareth Thomas, Claude Chelala, Peter W. Szlosarek. Gene expression analysis of argininosuccinate synthetase loss and the effects of pegylated arginine deiminase in malignant pleural mesothelioma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1431. doi:10.1158/1538-7445.AM2014-1431
Aldolase positively regulates of the canonical Wnt signaling pathway
Authors: Michal Caspi, Gili Perry, Nir Skalka, Shilhav Meisel, Anastasia Firsow, Maayan Amit, Rina Rosin-Arbesfeld
Journal: Molecular Cancer (2014)

The Wnt signaling pathway is an evolutionary conserved system, having pivotal roles during animal development. When over-activated, this signaling pathway is involved in cancer initiation and progression. The canonical Wnt pathway regulates the stability of β-catenin primarily by a destruction complex containing a number of different proteins, including Glycogen synthase kinase 3β (GSK-3β) and Axin, that promote proteasomal degradation of β-catenin. As this signaling cascade is modified by various proteins, novel screens aimed at identifying new Wnt signaling regulators were conducted in our laboratory. One of the different genes that were identified as Wnt signaling activators was Aldolase C (ALDOC). Here we report that ALDOC, Aldolase A (ALDOA) and Aldolase B (ALDOB) activate Wnt signaling in a GSK-3β-dependent mechanism, by disrupting the GSK-3β-Axin interaction and targeting Axin to the dishevelled (Dvl)-induced signalosomes that positively regulate the Wnt pathway thus placing the Aldolase proteins as novel Wnt signaling regulators.
Accidental poisoning with Malathion.
Authors: F H Ekin
Journal: BMJ (1971)

P-selectin glycoprotein ligand-1 (PSGL-1) is an adhesion molecule expressed on the surface of naïve, effector, and memory CD4<sup>+</sup> and CD8<sup>+</sup> T cells. We identified PSGL-1 to be an immune checkpoint inhibitor as antibody-mediated ligation of PSGL-1 promotes T cell exhaustion and deletion of PSGL-1 prevents chronic viral infection and inhibits tumor. To investigate the role of PSGL-1 signaling in the development of T cell responses, we assessed the differentiation state, expansion capacity, and glycolytic profile of PSGL-1-deficient T cells. PSGL-1<sup>+/−</sup> OT-II CD4<sup>+</sup> T cells demonstrated increased skewing towards IL-17A<sup>+</sup> T cells compared to wild-type OT-II CD4<sup>+</sup> T cells under T<sub>H</sub>17 conditions, and reduced IFNg<sup>+</sup> cells under both T<sub>H</sub>0 and T<sub>H</sub>1 conditions. In a B16-OVA tumor model, we observed increased IL-13<sup>+</sup> CD4<sup>+</sup> T cells among the intratumoral T cell compartment in PSGL-1<sup>−/−</sup> mice. <i>In vitro</i> activation with a sub-optimal dose of αCD3 of PSGL-1<sup>−/−</sup> OT-II CD4<sup>+</sup> T cells demonstrated increased expansion and expression of CD25 compared to wild-type OT-II CD4<sup>+</sup> T cells. Further, adoptively transferred <i>in vitro</i>-activated PSGL-1<sup>−/−</sup> CD4<sup>+</sup> T cells demonstrated greater expansion <i>in vivo</i> upon adoptive transfer into RAG<sup>−/−</sup> host mice. Using the Seahorse glycolysis stress test, we identified that both CD4<sup>+</sup> and CD8<sup>+</sup> PSGL-1<sup>−/−</sup> T cells demonstrate increased glycolysis after 72 hours of <i>in vitro</i> activation compared to wild-type T cells. Further, <i>in situ</i> activation of PSGL-1<sup>−/−</sup> CD8<sup>+</sup> T cells demonstrates that at both sub-optimal and optimal levels of αCD3 stimulation, PSGL-1<sup>−/−</sup> CD8<sup>+</sup>T cells have increased glycolysis and increased glycolytic capacity. Taken together, these data show that PSGL-1 signaling has an intrinsic and immediate role in the development of T cell responses.
Left Ventricular Mass and Risk of Stroke in an Elderly Cohort
Authors: Mahesh Bikkina
Journal: JAMA (1994)

<h3>Objective.</h3> —To evaluate the association of echocardiographically determined left ventricular mass (LVM) with incidence of stroke or transient ischemic attack in an elderly cohort. <h3>Design.</h3> —Cohort study with a follow-up period of 8 years. <h3>Setting.</h3> —Population-based sample. <h3>Subjects.</h3> —Elderly original cohort subjects of the Framingham Heart Study who were free of cerebrovascular disease and atrial fibrillation at the 16th biennial examination and who had adequate echocardiograms. This group consisted of 447 men (mean age, 67.8 years; range, 60 to 90 years) and 783 women (mean age, 69.2 years; range 59 to 90 years). <h3>Main Outcome Measures.</h3> —Age-adjusted 8-year incidence of stroke was examined as a function of baseline quartiles of LVM-to-height ratio. Proportional hazards regression was used in multivariate analyses to assess risk of stroke as a function of LVM-to-height ratio quartile, adjusting for age, sex, systolic blood pressure, hypertension treatment, diabetes, cigarette smoking, and blood lipid levels. <h3>Results.</h3> —Among the 1230 subjects eligible, 89 cerebrovascular disease events (62 strokes and 27 transient ischemic attacks) occurred during follow-up. In men, 8-year age-adjusted incidence of cerebrovascular events was 18.4% in the highest quartile of LVM-to-height ratio and 5.2% in the lowest quartile. Corresponding values in women were 12.2% and 2.9%. The hazard ratio for cerebrovascular events comparing highest to lowest quartile of LVM-to-height ratio was 2.72 (95% confidence interval [CI], 1.39 to 5.36) after adjusting for age, sex, systolic blood pressure, hypertension treatment, diabetes, cigarette smoking, and the ratio of total cholesterol to high-density lipoprotein cholesterol. After adjusting for age, sex, and cardiovascular disease risk factors, the hazard ratio for cerebrovascular events was 1.45 (95% CI, 1.17 to 1.80) for each quartile increment of LVM-to-height ratio. <h3>Conclusions.</h3> —Echocardiographically determined LVM-to-height ratio offers prognostic information beyond that provided by traditional cerebrovascular disease risk factors. Echocardiography provides information that facilitates identification of individuals at high risk for stroke and transient ischemic attack. (<i>JAMA</i>. 1994;272:33-36)
Autoimmune lymphoproliferative syndrome caused by a homozygous null FAS ligand (FASLG) mutation
Authors: Aude Magerus-Chatinet, Marie-Claude Stolzenberg, Nina Lanzarotti, Bénédicte Neven, Cécile Daussy, Capucine Picard, Nathalie Neveux, Mukesh Desai, Meghana Rao, Kanjaksha Ghosh, Manisha Madkaikar, Alain Fischer, Frédéric Rieux-Laucat
Journal: Journal of Allergy and Clinical Immunology (2012)
Breast self examination does not improve cancer survival
Authors: D. Josefson
Journal: BMJ (2002)

Teaching women breast self examination is not cost effective, nor does it lead to improvements in survival from breast cancer, according to a large, 10 year, randomised observational study conducted in Shanghai, China ( J Natl Cancer Inst 2002;94:1445-57).

Breast self examinations did, however, lead to earlier detection of breast lesions and increased the number of biopsies for benign breast lumps.

David Thomas and Roberta Ray and colleagues from the Fred Hutchinson Cancer Research Center in Seattle, Washington, in conjunction with Dao Li Goa and colleagues from the Shanghai Textile Industry Bureau in Shanghai, China, conducted a study to examine the …
Maternal Cigarette Smoking, Metabolic Gene Polymorphism, and Infant Birth Weight
Authors: Xiaobin Wang
Journal: JAMA (2002)

ContextLittle is known about genetic susceptibility to cigarette smoke in relation to adverse pregnancy outcomes.ObjectiveTo investigate whether the association between maternal cigarette smoking and infant birth weight differs by polymorphisms of 2 maternal metabolic genes: CYP1A1 and GSTT1.Design, Setting, and ParticipantsCase-control study conducted in 1998-2000 among 741 mothers (174 ever smokers and 567 never smokers) who delivered singleton live births at Boston Medical Center. A total of 207 cases were preterm or low-birth-weight infants and 534 were non–low-birth-weight, full-term infants (control).Main Outcome MeasureBirth weight, gestation, fetal growth by smoking status and CYP1A1 MspI (AA vs Aa and aa, where Aa and aa were combined because of small numbers of aa and similar results), and GSTT1 (present vs absent) genotypes.ResultsWithout consideration of genotype, continuous maternal smoking during pregnancy was associated with a mean reduction of 377 g (SE, 89 g) in birth weight (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.2-3.7). When CYP1A1 genotype was considered, the estimated reduction in birth weight was 252 g (SE, 111 g) for the AA genotype group (n = 75; OR, 1.3; 95% CI, 0.6-2.6), but was 520 g (SE, 124 g) for the Aa/aa genotype group (n = 43 for Aa, n = 6 for aa; OR, 3.2; 95% CI, 1.6-6.4). When GSTT1 genotype was considered, the estimated reduction in birth weight was 285 g (SE, 99 g) (OR, 1.7; 95% CI, 0.9-3.2) and 642 g (SE, 154 g) (OR, 3.5; 95% CI, 1.5-8.3) for the present and absent genotype groups, respectively. When both CYP1A1 and GSTT1 genotypes were considered, the greatest reduction in birth weight was found among smoking mothers with the CYP1A1 Aa/aa and GSTT1 absent genotypes (−1285 g; SE, 234 g; P&lt;.001). Among never smokers, genotype did not independently confer an adverse effect. A similar pattern emerged in analyses stratified by maternal ethnicity and in analyses for gestation.ConclusionsIn our study, maternal CYP1A1 and GSTT1 genotypes modified the association between maternal cigarette smoking and infant birth weight, suggesting an interaction between metabolic genes and cigarette smoking.
Fall in cholesterol after changes in composition of cooking oil in Mauritius
Authors: N Chandrasekharan, K. Sundram
Journal: BMJ (1997)

Appropriate treatment of autoimmune myocarditis following virus infection remains a major clinical problem. Induction of nasal tolerance may provide a new approach to treatment. However, the exact mechanism of nasal tolerance is unknown. To assess the mechanism of nasal tolerance, we examined the role of IL-10 in the induction and suppression of autoimmune myocarditis. First we showed that blocking IL-10 concurrent with nasal administration of Ag abolished the disease-suppressing effect of nasal tolerization. It also led to increased cardiac myosin-specific IL-1 and TNF-α production. Then we demonstrated that blocking IL-10 during the effector phase increased not only the incidence and severity of disease but also Ag-specific IL-2, IL-4, and TNF-α production as well as cardiac myosin-specific IgG1 and IgG2b production, whereas blocking IL-10 during the induction phase had no effect. This study implicates IL-10 in the induction of nasal tolerance and in limiting inflammation later during the disease process.