tbuckley/cabot-search huggingface dataset:
pH-Hp: implications for dyspepsia management
Authors: A Axon, N J Talley, S J O Veldhuyzen van Zanten
Journal: Gut (2002)

Introduction to the proceedings of the symposium on dyspepsia management, held in Geneva, Switzerland, December 1998.

Clinical trials using omeprazole began in 1983. Research since then, involving more than 50 000 patients, has shown that this drug is safe and well tolerated. It is consistently effective in the treatment of peptic ulcer disease and gastro-oesophageal reflux disease. It plays a pivotal role in the treatment of Helicobacter pylori infection. It is also valuable in prophylaxis for patients taking non-steroidal anti-inflammatory drugs and in the intensive care unit for stress ulcer prophylaxis. For all of these reasons, …
Human genetics, environment, and communities of color: ethical and social implications.
Authors: Julie Sze, Swati Prakash
Journal: Environmental Health Perspectives (2004)

A conference titled "Human Genetics, Environment, and Communities of Color: Ethical and Social Implications" and a workshop symposium titled "Human Genetics and Environmental Justice" were held by West Harlem Environmental Action, Inc., with cosponsorship by the National Institute of Environmental Health Sciences (NIEHS), the Community Outreach and Education Program of the NIEHS P30 Center for Environmental Health at the Mailman School of Public Health at Columbia University, New York, and the U.S. Environmental Protection Agency. The conference and symposium took place at Columbia University in New York City on 4-5 February 2002. Expert panels composed of public health practitioners, genetic researchers, ethicists, lawyers, social scientists, and community organizations were assembled to explore how genetic research will affect communities of color, specifically in environmental health research. The goal of the conference was to educate participants on the science and ethics of genetic research and to explore the potential benefits and pitfalls of genetic research vis-à-vis new trends in environmental health research, specifically with reference to communities of color. The goal of the symposium was to discuss the major perceptions and concerns for community-based environmental justice advocates and other communities of color regarding environmental health genetic research. The conference and symposium drew more than 300 participants and articulated important perspectives on the opportunities and challenges for environmental justice advocates and other communities of color posed by rapid advances in environmental health genetic research and toxicogenomics.
Phase III placebo controlled double blind randomized trial of radiation therapy for stage 2B-4A cervical cancer with immunomodulator Z-100: JGOG-DT101 study.
Authors: Keiichi Fujiwara, Yasuo Ohashi, Kazunori Ochiai, Kiichiro Noda
Journal: Journal of Clinical Oncology (2013)

5506 Background: We previously reported that the lower dose (0.2 μg) of immunomodulator Z-100 showed better overall survival (OS) compared to higher dose (40 μg) in patients with locally advanced cervical cancer who received radiation therapy (RT). Therefore, we conducted a placebo controlled double-blind randomized trial to elucidate the role of additive immunotherapy in standard RT. Methods: Patients of stages 2B to 4A squamous cell carcinoma of the uterine cervix, who were scheduled to receive standard RT with or without platinum-based chemotherapy, were eligible. Z-100 at 0.2 μg (Z) or placebo (P) was given subcutaneously twice a week during the RT, followed by maintenance therapy by administering either Z or P once every two weeks. Therapy was continued until disease progression or termination of the trial in2011. Primary endpoint was OS, secondary endpoints were recurrent-free survival (RFS), response rate (RR), and safety. Sample size was calculated by assuming 5-year survival rates (5YSR) as 60% in Arm Z and 38-44% for Arm P, (hazard ratio HR: 0.526-0.625), and was determined to be 120 patients in each arm. Results: Between 2004 and 2006, 249 patients were randomized. Total of 244 patients were eligible for safety analysis, and 243 patients were eligible for survival analysis. In Arm Z, 29 deaths were reported, and in Arm P, 42. 5YSR was 75.7% (95%CI: 66.4-82.8%) for Arm Z and 65.8 % (95%CI: 56.2-73.8%) for Arm P; HR was 0.646 (95%CI: 0.400-1.043). Survival benefit in Arm Z was observed regardless of chemoradiation or radiation alone. There were no differences between arms in terms of RR and RFS, and side effects. Neoplasms, including benign cases, observed were 4 in Arm Z, and 13 in Arm P. Conclusions: Immunomodulator Z-100, used as an adjuvant therapy after radiation, showed clinically significant improvement of OS in locally advanced cervical cancer, although the statistical power was less than anticipated because survival rates were unexpectedly higher than expected for both arms. Further exploration of Z-100 is warranted. Clinical trial information: C000000221.
URINARY NEOPTERIN, A USEFUL MARKER FOR AIDS?
Authors: M. Perna, F. Nitsch, G. Santelli, A. Marfella, G. Giraldo, E. Beth-Giraldo, J.A. Levy, M. Piazza, R. De Mercato, A. Chirianni, P.T. Cataldo, E. Giuliano, R. Cozzi
Journal: The Lancet (1985)
Drug-induced cholestasis
Authors: Manmeet S. Padda, Mayra Sanchez, Abbasi J. Akhtar, James L. Boyer
Journal: Hepatology (2011)

Recent progress in understanding the molecular mechanisms of bile formation and cholestasis have led to new insights into the pathogenesis of drug-induced cholestasis. This review summarizes their variable clinical presentations, examines the role of transport proteins in hepatic drug clearance and toxicity, and addresses the increasing importance of genetic determinants, as well as practical aspects of diagnosis and management. (HEPATOLOGY 2011;)
Using physical-chemistry-based substitution models in phylogenetic analyses of HIV-1 subtypes
Authors: J. M. Koshi, D. P. Mindell, R. A. Goldstein
Journal: Molecular Biology and Evolution (1999)

HIV-1 subtype phylogeny is investigated using a previously developed computational model of natural amino acid site substitutions. This model, based on Boltzmann statistics and Metropolis kinetics, involves an order of magnitude fewer adjustable parameters than traditional substitution matrices and deals more effectively with the issue of protein site heterogeneity. When optimized for sequences of HIV-1 envelope (env) proteins from a few specific subtypes, our model is more likely to describe the evolutionary record for other subtypes than are methods using a single substitution matrix, even a matrix optimized over the same data. Pairwise distances are calculated between various probabilistic ancestral subtype sequences, and a distance matrix approach is used to find the optimal phylogenetic tree. Our results indicate that the relationships between subtypes B, C, and D and those between subtypes A and H may be closer than previously thought.
Systemic bioactivity of inhaled fluticasone is not affected by the presence of emphysema
Authors: A Jain
Journal: Thorax (2004)

▴ Lipworth BJ, Lee DKC. The presence of emphysema does not affect the systemic bioactivity of inhaled fluticasone in severe chronic obstructive pulmonary disease. Br J Clin Pharmacol2004;57:388–92. [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] Inhaled corticosteroids reduce exacerbation frequency in COPD but it is not known whether the presence of emphysema, with decreased alveolar volume, results in impaired bioactivity. The systemic effects of fluticasone 2000 μg daily were compared in patients with COPD who did and did not have emphysema (COPDE and … [1]: {openurl}?query=rft.jtitle%253DBritish%2Bjournal%2Bof%2Bclinical%2Bpharmacology%26rft.stitle%253DBr%2BJ%2BClin%2BPharmacol%26rft.aulast%253DLee%26rft.auinit1%253DD.%2BK.%26rft.volume%253D57%26rft.issue%253D4%26rft.spage%253D388%26rft.epage%253D392%26rft.atitle%253DThe%2Bpresence%2Bof%2Bemphysema%2Bdoes%2Bnot%2Baffect%2Bthe%2Bsystemic%2Bbioactivity%2Bof%2Binhaled%2Bfluticasone%2Bin%2Bsevere%2Bchronic%2Bobstructive%2Bpulmonary%2Bdisease.%26rft_id%253Dinfo%253Adoi%252F10.1046%252Fj.1365-2125.2003.02026.x%26rft_id%253Dinfo%253Apmid%252F15025735%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1046/j.1365-2125.2003.02026.x&link_type=DOI [3]: /lookup/external-ref?access_num=15025735&link_type=MED&atom=%2Fthoraxjnl%2F59%2F6%2F482.atom [4]: /lookup/external-ref?access_num=000220272800003&link_type=ISI
Expression of the <i>Elm1</i> Gene, a Novel Gene of the CCN (Connective Tissue Growth Factor, Cyr61/Cef10, and Neuroblastoma Overexpressed Gene) Family, Suppresses In Vivo Tumor Growth and Metastasis of K-1735 Murine Melanoma Cells
Authors: Yasunobu Hashimoto, Nobuko Shindo-Okada, Masachika Tani, Yasuhiro Nagamachi, Kaori Takeuchi, Toshihiko Shiroishi, Hiroshi Toma, Jun Yokota
Journal: The Journal of Experimental Medicine (1998)

We previously isolated a partial cDNA fragment of a novel gene, Elm1 (expressed in low-metastatic cells), that is expressed in low-metastatic but not in high-metastatic K-1735 mouse melanoma cells. Here we determined the full-length cDNA structure of Elm1 and investigated the effect of Elm1 expression on growth and metastatic potential of K-1735 cells. The Elm1 gene encodes a predicted protein of 367 amino acids showing ∼40% amino acid identity with the CCN (connective tissue growth factor [CTGF], Cyr61/Cef10, neuroblastoma overexpressed gene [Nov]) family proteins, which consist of secreted cysteine-rich proteins with growth regulatory functions. Elm1 is also a cysteine-rich protein and contains a signal peptide and four domains conserved in the CCN family proteins. Elm1 was highly conserved, expressed ubiquitously in diverse organs, and mapped to mouse chromosome 15. High-metastatic K-1735 M-2 cells, which did not express Elm1, were transfected with an Elm1 expression vector, and several stable clones with Elm1 expression were established. The in vivo growth rates of cells expressing a high level of Elm1 were remarkably slower than those of cells expressing a low level of Elm1. Metastatic potential of transfectants was reduced in proportion to the level of Elm1 expression. Thus, Elm1 is a novel gene of CCN family that can suppress the in vivo growth and metastatic potential of K-1735 mouse melanoma cells.
Lack of simian immunodeficiency virus (SIV) specific IgA response in the intestine of SIV infected rhesus macaques
Authors: F Schafer
Journal: Gut (2002)

Background: Little is known about secretory immunity—the major defence mechanism at mucosal surfaces—in human immunodeficiency virus (HIV) infected patients, especially in the early stages of the disease. Aims: The aim of the study was to analyse mucosal immunoglobulin production and simian immunodeficiency virus (SIV) specific antibody response in the intestinal mucosa during the course of SIV infection in comparison with serum and saliva. Animals and methods: IgG, IgA, and IgM concentrations were determined in supernatants of short term cultured duodenal biopsies, serum, and saliva from SIV infected rhesus macaques (n=8) and controls (n=2) by ELISA at defined times before and after infection. Specific antibodies to SIV were detected by western blot and/or dot blot analysis. In addition, rectal swabs from two uninfected and 12 SIV infected rhesus macaques (seven without and five with enteritis) were analysed for albumin and IgG concentrations. Results: An increase in total intestinal IgG and a decrease in IgA were observed. SIV specific IgG or IgA responses were detectable as early as one week after SIV infection in the serum of seven of eight animals. In contrast, intestinal SIV specific IgG production was detected only four weeks after infection in six of eight animals, and intestinal SIV specific IgA was not produced in the intestine at any time point. In saliva, the secretory component on SIV specific IgA was only detected in one animal at week 24 after infection. Enteritis is frequent in SIV infected animals and results in a significant increase in albumin and IgG secretion into the intestinal lumen. Conclusion: Despite modest quantitative changes in mucosal immunglobulin production there was a total lack of SIV specific IgA synthesis in the intestine during SIV infection. This lack or disturbed secretory SIV specific IgA response at mucosal surfaces may explain the rapid and high HIV/SIV replication in this compartment. In addition, our investigations indicate secretion of serum proteins into intestinal fluids during SIV infection. Previous investigations using intestinal secretions or swabs for analysing quantitative and specific immunglobulins therefore should be interpreted with caution.
Hedgehog Signaling Is a Novel Therapeutic Target in Tamoxifen-Resistant Breast Cancer Aberrantly Activated by PI3K/AKT Pathway
Authors: Bhuvaneswari Ramaswamy, Yuanzhi Lu, Kun-yu Teng, Gerard Nuovo, Xiaobai Li, Charles L. Shapiro, Sarmila Majumder
Journal: Cancer Research (2012)

Endocrine resistance is a major challenge in the management of estrogen receptor (ER)-positive breast cancers. Although multiple mechanisms leading to endocrine resistance have been proposed, the poor outcome of patients developing resistance to endocrine therapy warrants additional studies. Here we show that noncanonical Hedgehog (Hh) signaling is an alternative growth promoting mechanism that is activated in tamoxifen-resistant tumors. Importantly, phosphoinositide 3-kinase inhibitor/protein kinase B (PI3K/AKT) pathway plays a key role in regulating Hh signaling by protecting key components of this pathway from proteasomal degradation. The levels of Hh-signaling molecules SMO and GLI1 and the targets were significantly elevated in tamoxifen-resistant MCF-7 cells and T47D cells. Serial passage of the resistant cells in mice resulted in aggressive tumors that metastasized to distant organs with concurrent increases in Hh marker expression and epithelial mesenchymal transition. RNAi-mediated depletion of SMO or GLI1 in the resistant cells resulted in reduced proliferation, clonogenic survival and delayed G(1)-S transition. Notably, treatment of resistant cells with PI3K inhibitors decreased SMO and GLI1 protein levels and activity that was rescued upon blocking GSK3β and proteasomal degradation. Furthermore, treatment of tamoxifen-resistant xenografts with anti-Hh compound GDC-0449 blocked tumor growth in mice. Importantly, high GLI1 expression correlated inversely with disease-free and overall survival in a cohort of 315 patients with breast cancer. In summary, our results describe a signaling event linking PI3K/AKT pathway with Hh signaling that promotes tamoxifen resistance. Targeting Hh pathway alone or in combination with PI3K/AKT pathway could therefore be a novel therapeutic option in treating endocrine-resistant breast cancer.
Novel Functional Sets of Lipid-Derived Mediators with Antiinflammatory Actions Generated from Omega-3 Fatty Acids via Cyclooxygenase 2–Nonsteroidal Antiinflammatory Drugs and Transcellular Processing
Authors: Charles N. Serhan, Clary B. Clish, Jessica Brannon, Sean P. Colgan, Nan Chiang, Karsten Gronert
Journal: The Journal of Experimental Medicine (2000)

Aspirin therapy inhibits prostaglandin biosynthesis without directly acting on lipoxygenases, yet via acetylation of cyclooxygenase 2 (COX-2) it leads to bioactive lipoxins (LXs) epimeric at carbon 15 (15-epi-LX, also termed aspirin-triggered LX [ATL]). Here, we report that inflammatory exudates from mice treated with ω-3 polyunsaturated fatty acid and aspirin (ASA) generate a novel array of bioactive lipid signals. Human endothelial cells with upregulated COX-2 treated with ASA converted C20:5 ω-3 to 18R-hydroxyeicosapentaenoic acid (HEPE) and 15R-HEPE. Each was used by polymorphonuclear leukocytes to generate separate classes of novel trihydroxy-containing mediators, including 5-series 15R-LX5 and 5,12,18R-triHEPE. These new compounds proved to be potent inhibitors of human polymorphonuclear leukocyte transendothelial migration and infiltration in vivo (ATL analogue &amp;gt; 5,12,18R-triHEPE &amp;gt; 18R-HEPE). Acetaminophen and indomethacin also permitted 18R-HEPE and 15R-HEPE generation with recombinant COX-2 as well as ω-5 and ω-9 oxygenations of other fatty acids that act on hematologic cells. These findings establish new transcellular routes for producing arrays of bioactive lipid mediators via COX-2–nonsteroidal antiinflammatory drug–dependent oxygenations and cell–cell interactions that impact microinflammation. The generation of these and related compounds provides a novel mechanism(s) for the therapeutic benefits of ω-3 dietary supplementation, which may be important in inflammation, neoplasia, and vascular diseases.
Thalamocortical Dysconnectivity in Schizophrenia
Authors: Neil D. Woodward, Haleh Karbasforoushan, Stephan Heckers
Journal: American Journal of Psychiatry (2012)

Objective The thalamus and cerebral cortex are connected via topographically organized, reciprocal connections. Previous studies have revealed thalamic abnormalities in schizophrenia; however, it is not known whether thalamocortical networks are differentially affected in the disorder. To explore this possibility, the authors examined functional connectivity in intrinsic low-frequency blood-oxygen-level-dependent (BOLD) signal fluctuations between major divisions of the cortex and thalamus using resting-state functional MRI (fMRI). Method Seventy-seven healthy subjects and 62 patients with schizophrenia underwent resting-state fMRI. To identify functional subdivisions of the thalamus, the authors parceled the cortex into six regions of interest: the prefrontal cortex, motor cortex/supplementary motor area, somatosensory cortex, temporal lobe, posterior parietal cortex, and occipital lobe. Mean BOLD time series were extracted for each region of interest and entered into a seed-based functional connectivity analysis. Results Consistent with previous reports, activity in distinct cortical areas correlated with specific, largely nonoverlapping regions of the thalamus in both healthy comparison subjects and schizophrenia patients. Direct comparison between groups revealed reduced prefrontal-thalamic connectivity and increased motor/somatosensory-thalamic connectivity in schizophrenia. The changes in connectivity were unrelated to local gray matter content within the thalamus and to antipsychotic medication dosage. No differences were observed in temporal, posterior parietal, or occipital cortex connectivity with the thalamus. Conclusions These findings establish differential abnormalities of thalamocortical networks in schizophrenia. The etiology of schizophrenia may disrupt the development of prefrontal-thalamic connectivity and refinement of somatomotor connectivity with the thalamus that occurs during brain maturation.
Skeletal muscle inflammation and nitric oxide in patients with COPD
Authors: M. Montes de Oca, S. H. Torres, J. De Sanctis, A. Mata, N. Hernández, C. Tálamo
Journal: European Respiratory Journal (2005)

In chronic obstructive pulmonary disease (COPD) the presence of systemic inflammation has been associated with peripheral muscle abnormalities and weight loss. To study whether inflammatory factors are important in these processes, the present study compared the skeletal muscle levels of nitrite, nitrate, nitrotyrosine, neuronal, endothelial and inducible nitric oxide synthases (nNOS, eNOS, and iNOS, respectively), and inflammatory markers (tumour necrosis factor (TNF)-α, CD154 and CD163) in 15 patients (forced expiratory volume in one second 43±11%) and 14 controls. All these markers were also compared between patients with normal and low body weight. Nitrite (12.5±2.6 versus 17.0±3.4 μmol·mg −1 protein), nitrate (20.7±2.4 versus 24.4±4.5 μmol·mg −1 protein) and eNOS (31.9±4.6 versus 43.6±7.5 ng·mg −1 protein) were lower in COPD patients than in controls. Nitrotyrosine (25.6±5.4 versus 6.6±3.3 ng·mg −1 protein), iNOS expression (32±9.5 versus 7.16±2.7 ng·mg −1 protein), TNF-α (257±160 versus 48.3±4.4 pg·mg −1 protein) and CD163 (6.4±2.1 versus 0.8±0.4 ng·mg −1 protein) were higher in COPD patients than in controls. CD154 levels were 15.7±7.0 ng·mg −1 protein in COPD patients and undetectable in controls. Similar levels of all these markers were observed in COPD patients with normal and low body weight. In conclusion, these findings suggest the presence of an inflammatory process in the muscle tissue of chronic obstructive pulmonary disease patients, and argue in favour of its participation in the pathogenesis of skeletal muscle abnormalities.
Mast cell degranulation induced by type 1 fimbriated Escherichia coli in mice.
Authors: R Malaviya, E Ross, B A Jakschik, S N Abraham
Journal: Journal of Clinical Investigation (1994)

The strategic location of mast cells at the host-environment interface and their ability to release potent mediators of inflammation have suggested that these cells may play a pivotal role in host defense against bacterial infection. The ability of the opportunistic pathogen, Escherichia coli, to induce degranulation of mast cells obtained from the mouse peritoneum was investigated. We determined that unlike a mutant derivative deficient in the FimH subunit of the fimbriae or nonfimbriated E. coli, type 1 fimbriated E. coli induced mast cell degranulation in vitro. The magnitude of mast cell degranulation was directly proportional to the number of adherent bacteria on the cell surface in the initial period of the interaction. Using a mouse model of bacterial peritonitis, we demonstrated mast cell degranulation and histamine release by type 1 fimbriated bacteria in vivo. Furthermore, beads coated with FimH but not with FimA, the major subunit of type 1 fimbriae, evoked mast cell release of histamine in vivo in amounts comparable to that elicited by type 1 fimbriated E. coli. These studies reveal that mast cells can be degranulated by interaction with type 1 fimbriated E. coli and that FimH, the mannose-binding component of the fimbriae, is a potent mast cell stimulant.
Activating FLT3 mutations in CD117/KIT+ T-cell acute lymphoblastic leukemias
Authors: Elisabeth Paietta, Adolfo A. Ferrando, Donna Neuberg, John M. Bennett, Janis Racevskis, Hillard Lazarus, Gordon Dewald, Jacob M. Rowe, Peter H. Wiernik, Martin S. Tallman, A. Thomas Look
Journal: Blood (2004)
Come forth CD1d: Hsp110 in the regulation of intestinal epithelial CD1d expression
Authors: Christopher V. Nicchitta
Journal: Journal of Clinical Investigation (2003)

CD1d, a nonclassical MHC class I–like molecule, is prominently expressed on intestinal epithelial cells and is thought to function in the regulation of intestinal intraepithelial lymphocyte activity. Hsp110, an abundant heat shock protein present in essentially all mammalian tissues, has now been shown to upregulate CD1d expression in colonic tissue culture cell lines. Might this abundant chaperone serve an autocrine function in the regulation of CD1d expression?
How are medical devices regulated in the European Union?
Authors: Elaine French-Mowat, Joanne Burnett
Journal: Journal of the Royal Society of Medicine (2012)

Medical devices cannot be placed on the European market without conforming to the strict safety requirements of the European Union; one of these requirements is the affixation of the CE conformity mark. This article is an overview of the CE marking process only; it is not a document that should be referred to on its own. All manufacturers wishing to gain a CE mark should refer to the official documents.