tbuckley/cabot-search huggingface dataset:
The 15q24/25 Susceptibility Variant for Lung Cancer and Chronic Obstructive Pulmonary Disease Is Associated with Emphysema
Authors: Diether Lambrechts, Ian Buysschaert, Pieter Zanen, Johan Coolen, Natacha Lays, Harry Cuppens, Harry J M Groen, Walter Dewever, Rob J van Klaveren, Johny Verschakelen, Cisca Wijmenga, Dirkje S Postma, Marc Decramer, Wim Janssens
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Rationale: Genome-wide association studies have identified genetic variants in the nicotinic acetylcholine receptor (nAChR) on chromosome 15q24/25 as a risk for nicotine dependence, lung cancer, and chronic obstructive pulmonary disease (COPD). Assessment of bronchial obstruction by spirometry, typically used for diagnosing COPD, fails, however, to detect emphysema.Objectives: To determine the association of the 15q24/25 locus with emphysema.Methods: The rs1051730 variant on 15q24/25 was genotyped in two independent white cohorts of 661 and 456 heavy smokers. Participants underwent pulmonary function tests and computed tomography (CT) of the chest, and took questionnaires assessing smoking behavior and health status.Measurements and Main Results: The rs1051730 A-allele correlated with reduced FEV1 and with increased susceptibility for bronchial obstruction with a pooled odds ratio (OR) of 1.33 (95% confidence interval [CI] = 1.11–1.61; P = 0.0026). In both studies a correlation between the rs1051730 A-allele and lung diffusing capacity (DlCO) and diffusing capacity per unit alveolar volume (Kco) was observed. Consistently, the rs1051730 A-allele conferred increased risk for emphysema as assessed by CT (P = 0.0097 and P = 0.019), with a pooled OR of 1.39 (CI = 1.15–1.68; P = 0.00051). Visual emphysema scores and scores based on densities quantified on CT were more pronounced in A-allele carriers, indicating that rs1051730 correlates with the severity of emphysema.Conclusions: The 15q24/25 locus in nAChR is associated with the presence and severity of emphysema. This association was independent of pack-years smoking, suggesting that nAChR is causally involved in alveolar destruction as a potentially shared pathogenic mechanism in lung cancer and COPD.
Hepatitis B surface antigen binds to human serum albumin cross-linked by transglutaminase
Authors: Swan N. Thung, De-Fa Wang, Thomas M. Fasy, Andrew Hood, Michael A. Gerber
Journal: Hepatology (1989)

It has been postulated that polymerized human serum albumin may play a role in the infection of hepatocytes by hepatitis B virus, because both the envelope of hepatitis B virus (HBsAg) and hepatocytes exhibit binding activity for human serum albumin after cross-linking by glutaraldehyde. Since glutaraldehyde-dependent cross-linking of albumin molecules is not likely to occur in vivo, we considered the possibility that albumin may be polymerized by the action of transglutaminase enzymes present in plasma as activated factor XIII or released into plasma from tissues. Guinea pig liver transglutaminase covalently cross-linked human serum albumin molecules into dimers, trimers and polymers up to hexamers as shown by polyacrylamide gel electrophoresis in sodium dodecyl sulfate. HBsAg particles bound transglutaminase-cross-linked as well as glutaralde-hyde-cross-linked human serum albumin as demonstrated by radioimmunoassay and immunoelectron microscopy. The binding was blocked by preincubation of HBsAg with transglutaminase-or glutaraldehyde-cross-linked human serum albumin, anti-HBs or monoclonal anti-pre-S2, but not by polymerized bovine or rat serum albumin or by monomeric human serum albumin. These data indicate that HBsAg particles contain specific binding sites for transglutaminase-cross-linked human serum albumin, but it remains to be determined whether the albumin polymers play a role in the attachment of hepatitis B virus to hepatocytes.
Inducible Nitric Oxide Is Essential for Host Control of Persistent but Not Acute Infection with the Intracellular Pathogen <i>Toxoplasma gondii</i>
Authors: Tanya M. Scharton-Kersten, George Yap, Jeanne Magram, Alan Sher
Journal: The Journal of Experimental Medicine (1997)

The induction by IFN-γ of reactive nitrogen intermediates has been postulated as a major mechanism of host resistance to intracellular pathogens. To formally test this hypothesis in vivo, the course of Toxoplasma gondii infection was assessed in nitric oxide synthase (iNOS)−/− mice. As expected, macrophages from these animals displayed defective microbicidal activity against the parasite in vitro. Nevertheless, in contrast to IFN-γ−/− or IL-12 p40−/− animals, iNOSdeficient mice survived acute infection and controlled parasite growth at the site of inoculation. This early resistance was ablated by neutralization of IFN-γ or IL-12 in vivo and markedly diminished by depletion of neutrophils, demonstrating the existence of previously unappreciated NO independent mechanisms operating against the parasite during early infection. By 3-4 wk post infection, however, iNOS knockout mice did succumb to T. gondii. At that stage parasite expansion and pathology were evident in the central nervous system but not the periphery suggesting that the protective role of nitric oxide against this intracellular infection is tissue specific rather than systemic.
Efficacy of a new once-daily long-acting inhaled 2-agonist indacaterol versus twice-daily formoterol in COPD
Authors: R. Dahl, K. F. Chung, R. Buhl, H. Magnussen, V. Nonikov, D. Jack, P. Bleasdale, R. Owen, M. Higgins, B. Kramer
Journal: Thorax (2010)

<h3>Background</h3> Indacaterol is a long-acting inhaled β<sub>2</sub>-agonist (LABA) for the treatment of chronic obstructive pulmonary disease (COPD). In previous studies, indacaterol provided 24 h bronchodilation on once-daily dosing with a fast onset of action. This study compared the efficacy and safety of indacaterol with the twice-daily LABA formoterol and placebo over 1 year. <h3>Methods</h3> Patients with moderate to severe COPD were randomised to receive once-daily indacaterol 300 μg (n=437) or 600 μg (n=428), twice-daily formoterol 12 μg (n=435) or placebo (n=432) for 52 weeks in a double-blind double-dummy parallel group study. The primary efficacy variable was forced expiratory volume in 1 s (FEV<sub>1</sub>) measured 24 h postdose after 12 weeks (indacaterol vs placebo). Other outcomes included dyspnoea (transition dyspnoea index, TDI), use of as-needed salbutamol, symptom-based measures recorded on diary cards, exacerbations, health status (St George9s Respiratory Questionnaire), BODE index (body mass index, obstruction, dyspnoea, exercise), safety and tolerability. <h3>Results</h3> Indacaterol increased 24 h postdose FEV<sub>1</sub> after 12 weeks by 170 ml (both doses) versus placebo and by 100 ml versus formoterol (all p&lt;0.001). These significant differences were maintained at 52 weeks. Symptomatic outcomes were improved compared with placebo with all active treatments, and indacaterol was more effective than formoterol in improving TDI score and reducing the need for as-needed salbutamol. Indacaterol was well tolerated and had a good overall safety profile, including minimal impact on QTc interval and systemic β<sub>2</sub>-mediated events. <h3>Conclusions</h3> Once-daily indacaterol is an effective 24 h bronchodilator that improves symptoms and health status and confers clinical improvements over a twice-daily 12 h LABA as a treatment for patients with moderate to severe COPD. <h3>Trial registration number</h3> NCT 00393458.
THE CURRENT MANAGEMENT OF CARCINOMA OF THE HEAD OF THE PANCREAS
Authors: John L. Cameron
Journal: Annual Review of Medicine (1995)

▪ Abstract Carcinoma of the head of the pancreas can be diagnosed and staged effectively by computed tomography (CT) scan and by visceral angiography. If the tumor appears to be resectable, no further studies such as percutaneous biopsy are required. Pancreaticoduodenectomy is the only potentially curable treatment. This operation can be performed with a hospital mortality rate of approximately 2%. If the resection is curative, five-year survival in excess of 20% can be anticipated. Utilizing multivariate analysis, negative lymph node status, the absence of microscopic evidence of blood vessel involvement, and two or fewer blood transfusions during surgery are all independent predictors of long-term survival. Adjuvant therapy is effective and should be used routinely.
Prevalence of the TM6SF2 variant and non-alcoholic fatty liver disease in Chinese
Authors: Vincent Wai-Sun Wong, Grace Lai-Hung Wong, Chi-Hang Tse, Henry Lik-Yuen Chan
Journal: Journal of Hepatology (2014)

Non-alcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease worldwide and may progress to cirrhosis and hepatocellular carcinoma [1–3]. A recent exome-wide association study identified the TM6SF2 variant (encoding p.Glu167Lys) as a novel locus associated with higher liver fat level [4]. The variant is associated with decreased hepatic secretion of very-low-density lipoprotein and higher risk of myocardial infarction [4,5].
Initial and Cyclic Recruitment of Ovarian Follicles*
Authors: Elizabeth A. McGee, Aaron J. W. Hsueh
Journal: Endocrine Reviews (2000)

Mammalian ovaries consist of follicles as basic functional units. The total number of ovarian follicles is determined early in life, and the depletion of this pool leads to reproductive senescence. Each follicle develops to either ovulate or, more likely, to undergo degeneration. The dynamics of ovarian follicle development have interested endocrinologists and developmental biologists for many years. With the advent of assisted reproductive techniques in humans, the possibility of regulating follicle development in vivo and in vitro has gained clinical relevance. In this review, we focus upon key branching points during the development of ovarian follicles as well as factors involved in determining the eventual destiny of individual follicles. We discuss inconsistencies in the literature regarding the definitions of follicle recruitment and selection and propose to name the two major steps of follicle development as initial and cyclic recruitment, respectively. Because some of these disparities have arisen due to differences in the animal systems studied, we also compare the development of the ovarian follicles of both humans and rats. We also review the status of knowledge of several puzzling clinical issues that may provide important clues toward unlocking the mechanisms of follicle development.
Increased collagen synthesis and decreased collagen degradation in right ventricular hypertrophy induced by pressure overload
Authors: J. E Bishop, S. Rhodes, G. J Laurent, R. B Low, W. S Stirewalt
Journal: Cardiovascular Research (1994)

Journal Article Increased collagen synthesis and decreased collagen degradation in right ventricular hypertrophy induced by pressure overload Get access Jill E Bishop, Jill E Bishop Biochemistry Unit, National Heart and Lung Institute, Manresa Road, London SW3 6LR, United Kingdom: J E Bishop, G J Laurent; Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, Vermont, USA: S Rhodes, R B Low, W S Stirewalt. Correspondence to Dr Bishop. Search for other works by this author on: Oxford Academic PubMed Google Scholar Suzanne Rhodes, Suzanne Rhodes Biochemistry Unit, National Heart and Lung Institute, Manresa Road, London SW3 6LR, United Kingdom: J E Bishop, G J Laurent; Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, Vermont, USA: S Rhodes, R B Low, W S Stirewalt. Correspondence to Dr Bishop. Search for other works by this author on: Oxford Academic PubMed Google Scholar Geoffrey J Laurent, Geoffrey J Laurent Biochemistry Unit, National Heart and Lung Institute, Manresa Road, London SW3 6LR, United Kingdom: J E Bishop, G J Laurent; Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, Vermont, USA: S Rhodes, R B Low, W S Stirewalt. Correspondence to Dr Bishop. Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert B Low, Robert B Low Biochemistry Unit, National Heart and Lung Institute, Manresa Road, London SW3 6LR, United Kingdom: J E Bishop, G J Laurent; Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, Vermont, USA: S Rhodes, R B Low, W S Stirewalt. Correspondence to Dr Bishop. Search for other works by this author on: Oxford Academic PubMed Google Scholar William S Stirewalt William S Stirewalt Biochemistry Unit, National Heart and Lung Institute, Manresa Road, London SW3 6LR, United Kingdom: J E Bishop, G J Laurent; Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, Vermont, USA: S Rhodes, R B Low, W S Stirewalt. Correspondence to Dr Bishop. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 28, Issue 10, October 1994, Pages 1581–1585, https://doi.org/10.1093/cvr/28.10.1581 Published: 01 October 1994 Article history Received: 17 February 1994 Accepted: 25 July 1994 Published: 01 October 1994
THE PROTECTION OF PATHOGENIC MICROORGANISMS BY LIVING TISSUE CELLS
Authors: Peyton Rous, F. S. Jones
Journal: The Journal of Experimental Medicine (1916)

1. Living phagocytes are able to protect ingested organisms from the action of destructive substances in the surrounding fluid, and even from a strong homologous antiserum. 2. There is evidence that the protection by phagocytes is largely if not entirely conditioned on their being alive. 3. These facts should be taken into consideration in the study of diseases caused by infectious agents capable of living within tissue cells.
Histone Deacetylase 1 Gene Expression and Sensitization of Multidrug-Resistant Neuroblastoma Cell Lines to Cytotoxic Agents by Depsipeptide
Authors: Nino Keshelava, Elai Davicioni, Zesheng Wan, Lingyun Ji, Richard Sposto, Timothy J. Triche, C. Patrick Reynolds
Journal: JNCI Journal of the National Cancer Institute (2007)

Genes that are overexpressed in multidrug-resistant neuroblastomas relative to drug-sensitive neuroblastomas may provide targets for modulating drug resistance.We used microarrays to compare the gene expression profile of two drug-sensitive neuroblastoma cell lines with that of three multidrug-resistant neuroblastoma cell lines. RNA expression of selected overexpressed genes was quantified in 17 neuroblastoma cell lines by reverse transcription-polymerase chain reaction (RT-PCR). Small-interfering RNAs (siRNAs) were used for silencing gene expression. Cytotoxicity of melphalan, carboplatin, etoposide, and vincristine and cytotoxic synergy (expressed as combination index calculated by CalcuSyn software, where combination index < 1 indicates synergy and > 1 indicates antagonism) were measured in cell lines with a fluorescence-based assay of cell viability. All statistical tests were two-sided.A total of 94 genes were overexpressed in the multidrug-resistant cell lines relative to the drug-sensitive cell lines. Nine genes were selected for RT-PCR analysis, of which four displayed higher mRNA expression in the multidrug-resistant lines than in the drug-sensitive lines: histone deacetylase 1 (HDAC1; 2.3-fold difference, 95% confidence interval [CI] = 1.0-fold to 3.5-fold, P = .025), nuclear transport factor 2-like export factor (4.2-fold difference, 95% CI = 1.7-fold to 7.6-fold, P = .0018), heat shock 27-kDa protein 1 (2.5-fold difference, 95% CI = 1.0-fold to 87.7-fold, P = .028), and TAF12 RNA polymerase II, TATA box-binding protein-associated factor, 20 kDa (2.2-fold, 95% CI = 0.9-fold to 6.0-fold, P = .051). siRNA knockdown of HDAC1 gene expression sensitized CHLA-136 neuroblastoma cells to etoposide up to fivefold relative to the parental cell line or scrambled siRNA-transfected cells (P<.001). Cytotoxicity of the histone deacetylase inhibitor depsipeptide was tested in combination with melphalan, carboplatin, etoposide, or vincristine in five multidrug-resistant neuroblastoma cell lines, and synergistic cytotoxicity was demonstrated at a 90% cell kill of treated cells (combination index < 0.8) in all cell lines.High HDAC1 mRNA expression was associated with multidrug resistance in neuroblastoma cell lines, and inhibition of HDAC1 expression or activity enhanced the cytotoxicity of chemotherapeutic drugs in multidrug-resistant neuroblastoma cell lines. Thus, HDAC1 is a potential therapeutic target in multidrug-resistant neuroblastoma.
Impact of Baseline Renal Function on the Efficacy and Safety of Aliskiren Added to Losartan in Patients With Type 2 Diabetes and Nephropathy
Authors: Frederik Persson, Julia B. Lewis, Edmund J. Lewis, Peter Rossing, Norman K. Hollenberg, Hans-Henrik Parving
Journal: Diabetes Care (2010)

OBJECTIVE Proteinuric diabetic patients with reduced glomerular filtration rate (GFR) are at high risk of renal and cardiovascular disease progression and treatment-related adverse events. This post hoc analysis assessed the efficacy and safety of aliskiren added to the maximal recommended dose of losartan according to baseline estimated GFR (eGFR) (stage 1–3 chronic kidney disease [CKD]). RESEARCH DESIGN AND METHODS In the Aliskiren in the Evaluation of Proteinuria in Diabetes (AVOID) study, 599 hypertensive patients with type 2 diabetes and nephropathy received 6 months of aliskiren (150 mg daily titrated to 300 mg daily after 3 months) or placebo added to 100 mg losartan and optimal antihypertensive therapy. Exclusion criteria included eGFR &amp;lt;30 ml/min per 1.73 m2 and serum potassium &amp;gt;5.1 mmol/l. RESULTS Baseline characteristics were similar between treatment groups in all CKD stages. The antiproteinuric effects of aliskiren were consistent across CKD stages (19, 22, and 18% reduction). In the stage 3 CKD group, baseline serum creatinine levels were equal, but renal dysfunction, prespecified as a postrandomization serum creatinine elevation &amp;gt;176.8 μmol/l (2.0 mg/dl) occurred more frequently in the placebo group (29.2 vs. 13.6%, P = 0.032). Serum potassium elevations &amp;gt;5.5 mmol/l (based on a single measurement) were more frequent with aliskiren (22.5 vs. 13.6%) in stage 3 CKD. Adverse event rates were similar between treatments, irrespective of CKD stage. CONCLUSIONS Aliskiren added to losartan reduced albuminuria and renal dysfunction and was well tolerated, except for hyperkalemia (stage 3), independent of baseline CKD stage in patients with type 2 diabetes, hypertension, and nephropathy.
Nuclear localization and antisense effect of PNA internalized by ASGP-R-mediated endocytosis with protein/DNA conjugates
Authors: Tsutomu Ishihara, Arihiro Kano, Kentaro Obara, Minako Saito, Xuesi Chen, Tae Gwan Park, Toshihiro Akaike, Atsushi Maruyama
Journal: Journal of Controlled Release (2010)
Intensive Respiratory Care
Journal: Thorax (1993)

Beer, EdwardsOne of the nodular deposits of amyloid showing dichroism in polarised light.Stain: Congo red.Original magnification x 100, reduced to 75% in origination.disease.iAMost deposits are asymptomatic, some presenting as nodular shadows on chest radiography.5In most cases the amyloid is of AL type and confined to the lungs.'468In this report nodular pulmonary deposits of AA (reactive systemic) amyloid were seen in a patient with active Crohn's disease.The amy- loid was restricted to the pulmonary nodules with none in organs customarily involved in reactive sytemic or senile amyloidosis.
B cells expressing CD11b effectively inhibit CD4+ T‐cell responses and ameliorate experimental autoimmune hepatitis in mice
Authors: Xiaoming Liu, Xuechao Jiang, Ronghua Liu, Luman Wang, Tingting Qian, Yijie Zheng, Yuting Deng, Enyu Huang, Fengkai Xu, Ji‐Yang Wang, Yiwei Chu
Journal: Hepatology (2015)

Increasing evidence in recent years has suggested that B cells act as a crucial regulator in autoimmune diseases. However, little is known about their role in autoimmune hepatitis (AIH) and the underlying regulatory mechanisms. In this study, we show that B cells ameliorated experimental AIH (EAH) by suppressing CD4+ T-cell responses and that CD11b expression on B cells was required for the regulatory function of B cells. In vitro studies reveal that the suppressive function of CD11b was mediated by the impairment of T-cell antigen receptor (TCR) signaling transduction and the promotion of TCR down-regulation. Moreover, we show that the increased CD11b expression on B cells was interleukin (IL)-10 dependent and that additional IL-10 stimulation promoted CD11b expression on B cells, thereby enhancing B-cell regulatory effects.These findings reveal a previously unrecognized role for CD11b in B-cell regulatory function and its protective effect on EAH.
Ulcer, gastric surgery and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case–Control Consortium (PanC4)
Authors: C. Bosetti, E. Lucenteforte, P.M. Bracci, E. Negri, R.E. Neale, H.A. Risch, S.H. Olson, S. Gallinger, A.B. Miller, H.B. Bueno-de-Mesquita, R. Talamini, J. Polesel, P. Ghadirian, P.A. Baghurst, W. Zatonski, E. Fontham, E.A. Holly, Y.T. Gao, H. Yu, R.C. Kurtz, M. Cotterchio, P. Maisonneuve, M.P. Zeegers, E.J. Duell, P. Boffetta, C. La Vecchia
Journal: Annals of Oncology (2013)
Lymphatic Mapping and Sentinel Node Identification in Patients With Cervix Cancer Undergoing Radical Hysterectomy and Pelvic Lymphadenectomy
Authors: Charles Levenback, Robert L. Coleman, Thomas W. Burke, W. Michael Lin, William Erdman, Michael Deavers, Ebrahim S. Delpassand
Journal: Journal of Clinical Oncology (2002)

PURPOSE: The purpose of this study was to determine the feasibility of sentinel node identification in patients with invasive cervix cancer undergoing radical hysterectomy and pelvic lymphadenectomy using preoperative and intraoperative lymphatic mapping. PATIENTS AND METHODS: Thirty-nine patients at two institutions were enrolled onto this institutional review board–approved study. All underwent preoperative lymphoscintigraphy and intraoperative lymphatic mapping with blue dye and a handheld gamma probe. Radical hysterectomy was aborted in four patients because metastatic disease was discovered on frozen section analysis of the sentinel node. RESULTS: Preoperative lymphoscintigraphy revealed at least one sentinel node in 33 patients (85%), including 21 (55%) with bilateral sentinel nodes. All 39 patients had at least one sentinel node identified intraoperatively. Eighty percent of sentinel nodes were in three pelvic locations: iliac, obturator, and parametrial (in descending order of frequency). The remaining sentinel nodes were in the common iliac and para-aortic nodal basins. A total of 132 nodes were identified clinically as sentinel nodes; 65 (49%) were both blue and hot, 35 (27%) were blue only, and 32 (24%) were hot only. Eight patients (21%) had metastatic disease. In five of these patients, sentinel nodes were the only positive lymph nodes. One patient had false-negative sentinel nodes. She had four microscopically positive parametrial nodes that were resected in continuity with the uterus. The sensitivity of the sentinel node was 87.5% and the negative predictive value was 97%. CONCLUSION: Preoperative lymphoscintigraphy and intraoperative lymphatic mapping were highly successful at identifying sentinel nodes in patients undergoing radical hysterectomy.