tbuckley/cabot-search huggingface dataset:
Endogenous annexin A1 is a novel protective determinant in nonalcoholic steatohepatitis in mice
Authors: Irene Locatelli, Salvatore Sutti, Aastha Jindal, Marco Vacchiano, Cristina Bozzola, Chris Reutelingsperger, Dennis Kusters, Stefania Bena, Maurizio Parola, Claudia Paternostro, Elisabetta Bugianesi, Simon McArthur, Emanuele Albano, Mauro Perretti
Journal: Hepatology (2014)

Annexin A1 (AnxA1) is an effector of the resolution of inflammation and is highly effective in terminating acute inflammatory responses. However, its role in chronic settings is less investigated. Because changes in AnxA1 expression within adipose tissue characterize obesity in mice and humans, we queried a possible role for AnxA1 in the pathogenesis of nonalcoholic steatohepatitis (NASH), a disease commonly associated with obesity. NASH was induced in wild-type (WT) and AnxA1 knockout (AnxA1 KO) C57BL/6 mice by feeding a methionine-choline deficient (MCD) diet up to 8 weeks. In MCD-fed WT mice, hepatic AnxA1 increased in parallel with progression of liver injury. This mediator was also detected in liver biopsies from patients with NASH and its degree of expression inversely correlated with the extent of fibrosis. In both humans and rodents, AnxA1 production was selectively localized in liver macrophages. NASH in AnxA1 KO mice was characterized by enhanced lobular inflammation resulting from increased macrophage recruitment and exacerbation of the M1 phenotype. Consistently, in vitro addition of recombinant AnxA1 to macrophages isolated from NASH livers down-modulated M1 polarization through stimulation of interleukin-10 production. Furthermore, the degree of hepatic fibrosis was enhanced in MCD-fed AnxA1 KO mice, an effect associated with augmented liver production of the profibrotic lectin, galectin-3. Accordingly, AnxA1 addition to isolated hepatic macrophages reduced galectin-3 expression. Conclusions : Macrophage-derived AnxA1 plays a functional role in modulating hepatic inflammation and fibrogenesis during NASH progression, suggesting the possible use of AnxA1 analogs for therapeutic control of this disease. (Hepatology 2014;60:531–544)
The Cognitive and Negative Symptoms in Schizophrenia Trial (CONSIST): The Efficacy of Glutamatergic Agents for Negative Symptoms and Cognitive Impairments
Authors: Robert W. Buchanan, Daniel C. Javitt, Stephen R. Marder, Nina R. Schooler, James M. Gold, Robert P. McMahon, Uriel Heresco-Levy, William T. Carpenter
Journal: American Journal of Psychiatry (2007)

Patients with schizophrenia frequently present with negative symptoms and cognitive impairments for which no effective treatments are known. Agents that act at the glycine site of the N-methyl-D-aspartic acid (NMDA) glutamatergic receptor have been suggested as promising treatments for moderate to severe negative symptoms and cognitive impairments.The Cognitive and Negative Symptoms in Schizophrenia Trial (CONSIST) was a 16-week double-blind, double-dummy, parallel group, randomized clinical trial of adjunctive glycine, D-cycloserine, or placebo conducted at four sites in the United States and one site in Israel. The participants were 157 inpatients and outpatients who met DSM-IV criteria for schizophrenia or schizoaffective disorder and retrospective and prospective criteria for moderate to severe negative symptoms without marked positive, depressive, or extrapyramidal symptoms. The primary outcome measures were the average "rate of change" of Scale for the Assessment of Negative Symptoms (SANS) total scores and change in the average cognitive domain z scores.There were no significant differences in change in the SANS total score between glycine and placebo subjects or D-cycloserine and placebo subjects. A prespecified test for the site-by-treatment-by-time interaction was significant in post hoc tests. One site had greater reduction in the SANS total score for patients receiving D-cycloserine relative to patients receiving placebo. A second site had greater reduction in the SANS total score for placebo patients compared with glycine patients. There were no significant differences between glycine and placebo or D-cycloserine and placebo subjects on the average cognition z score.The study results suggest that neither glycine nor D-cycloserine is a generally effective therapeutic option for treating negative symptoms or cognitive impairments.
Clinical dose and adverse effects of topical steroids in daily management of atopic dermatitis
Authors: M. Furue, H. Terao, W. Rikihisa, K. Urabe, N. Kinukawa, Y. Nose, T. Koga
Journal: British Journal of Dermatology (2003)

Journal Article Clinical dose and adverse effects of topical steroids in daily management of atopic dermatitis Get access M. Furue, M. Furue Department of Dermatology and Masutaka Furue MD E‐mail: furue@dermatol.med.kyushu‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar H. Terao, H. Terao Department of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar W. Rikihisa, W. Rikihisa Department of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar K. Urabe, K. Urabe Department of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar N. Kinukawa, N. Kinukawa Department of Medical Information Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3‐1‐1, Higashi‐ku, Fukuoka 812‐8582, Japan Search for other works by this author on: Oxford Academic Google Scholar Y. Nose, Y. Nose Department of Medical Information Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3‐1‐1, Higashi‐ku, Fukuoka 812‐8582, Japan Search for other works by this author on: Oxford Academic Google Scholar T. Koga T. Koga Department of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 148, Issue 1, 1 January 2003, Pages 128–133, https://doi.org/10.1046/j.1365-2133.2003.04934.x Published: 01 January 2003 Article history Accepted: 27 February 2002 Published: 01 January 2003
Prevalence and incidence of hyperplastic polyps and adenomas in familial colorectal cancer: correlation between the two types of colon polyps
Authors: A Liljegren
Journal: Gut (2003)

Colorectal adenomas are recognised as precursors of colorectal carcinomas. The significance of hyperplastic (metaplastic) colorectal polyps is unknown. The relationship between hyperplastic polyps and adenomas, and the prevalence and incidence of these lesions were evaluated in individuals predisposed to familial colorectal cancer.A total of 299 individuals participating in our surveillance programme during 1990-2000 were retrospectively evaluated. Subjects were classified into three groups: hereditary non-polyposis syndrome (HNPCC) (n=108), hereditary colorectal cancer (HCRC) (n=127), and individuals with empirical risk estimates-two close relatives (TCR) (n=64). Findings from 780 colonoscopies were evaluated regarding prevalence and incidence of hyperplastic polyps and adenomas. Correlations between hyperplastic polyps and adenomas were calculated by Pearson correlation.In total, 292 hyperplastic polyps and 186 adenomas were observed in 98 and 90 individuals, respectively. A positive correlation was found between the numbers of hyperplastic polyps and adenomas (r=0.40; p<0.001). Correlations between adenomas and hyperplastic polyps were similar in the three groups. The risk of detecting new hyperplastic polyps (odds ratio 5.41) or adenomas (OR 2.56) increased significantly when there was a positive finding at first colonoscopy.Hyperplastic polyps as well as adenomas may identify individuals with a high risk of colorectal cancer. This information is important when these individuals are selected and included in tailored surveillance programmes.
Neutrophil elastase cleaves C3bi on opsonized pseudomonas as well as CR1 on neutrophils to create a functionally important opsonin receptor mismatch.
Authors: M F Tosi, H Zakem, M Berger
Journal: Journal of Clinical Investigation (1990)

Neutrophil elastase has been implicated as a factor that impairs local host defenses in chronic Pseudomonas aeruginosa (Pa) lung infection in cystic fibrosis (CF). We recently showed that this enzyme cleaves the C3b receptor, CR1, from neutrophils (PMN) in the lungs of infected CF patients. The C3bi receptor on these cells, CR3, is resistant to elastase. We now show that purified neutrophil elastase markedly impairs complement-mediated PMN-Pa interactions including phagocytosis of opsonized Pa, stimulation by opsonized Pa of PMN superoxide production, and killing of opsonized Pa by PMN. When PMN and opsonized Pa were treated separately with elastase, additive levels of inhibition were observed in each of the above assays. The effects on the bacteria were due to cleavage of the bound C3bi from the surface of opsonized Pa by neutrophil elastase. C3bi was also cleaved by pseudomonas elastase, or bronchoalveolar lavage fluid from CF patients with chronic Pa lung infection. Inhibitors of neutrophil elastase eliminated C3bi cleavage by BAL fluid, while inhibitors of pseudomonas elastase had no effect. Blocking CR1 and CR3 on PMN with specific monoclonal antibodies reduced phagocytosis of opsonized Pa to an extent similar to that caused by elastase cleavage of CR1 on PMN and C3bi on Pa. We conclude that neutrophil elastase in the lungs of chronically infected CF patients cleaves C3bi from opsonized Pa as well as CR1 from PMN, creating an "opsonin-receptor mismatch" that severely impairs complement-mediated phagocytic host defenses against these bacteria.
Narrowing and genomic annotation of the commonly deleted region of the 5q− syndrome
Authors: Jacqueline Boultwood, Carrie Fidler, Amanda J. Strickson, Fiona Watkins, Susana Gama, Lyndal Kearney, Sabrina Tosi, Arek Kasprzyk, Jan-Fang Cheng, Rina J. Jaju, James S. Wainscoat
Journal: Blood (2002)
Left ventricular ejection performance, wall stress, and contractile state in aortic regurgitation before and after aortic valve replacement.
Authors: K Taniguchi, S Nakano, Y Kawashima, K Sakai, T Kawamoto, S Sakaki, J Kobayashi, S Morimoto, H Matsuda
Journal: Circulation (1990)

Left ventricular ejection performance, wall stress, and contractile state were evaluated in 35 patients with chronic aortic regurgitation. Cineangiography and pressure measurements were obtained before and a mean of 26 months after aortic valve replacement, and data were compared with those from 30 normal control subjects. The relation between quantitative changes in wall stress and changes in ejection fraction after surgery was determined. Preoperatively, end-systolic stress was elevated in patients with aortic regurgitation (218 +/- 45 vs. 160 +/- 23 kdynes/cm2 [mean +/- SD] for control subjects, p less than 0.01), and ejection fraction was depressed (0.46 +/- 0.11 vs. 0.65 +/- 0.05, p less than 0.01). End-systolic stress decreased postoperatively (151 +/- 41 kdynes/cm2, p less than 0.01) and ejection fraction increased (0.58 +/- 0.11, p less than 0.01). The magnitude of increase in ejection fraction correlated significantly and negatively (r = -0.65) with the quantitative change in end-systolic stress after surgery. Contractile function, as assessed by the ejection phase index-end-systolic stress relation, did not significantly change: 23 of 35 patients preoperatively and 18 of 35 patients postoperatively had values that clearly fell below the 95% confidence limit of the ejection fraction-end-systolic stress relation for controls. After surgery, individual ejection fraction-end-systolic stress relationships demonstrated a shift parallel to the regression curve for the control subjects. Moreover, persistent postoperative left ventricular hypertrophy was significantly associated with persistent contractile dysfunction. Thus, late improvement in left ventricular ejection performance after aortic valve replacement can be attributed to the reduction in end-systolic stress. Contractile function itself was not improved by surgery. Persistent postoperative hypertrophy may be a marker for myocardial contractile dysfunction.
Involvement of myosin light-chain kinase in chloride-sensitive Ca2+ influx in porcine aortic endothelial cells
Authors: Quang-Kim Tran, Hiroshi Watanabe, Xu-Xia Zhang, Reiko Takahashi, Ryuzo Ohno
Journal: Cardiovascular Research (1999)

Objectives: This study was designed to investigate the involvement of myosin light-chain kinase (MLCK) in bradykinin- and thapsigargin-induced changes in intracellular Cl− and Ca2+ concentrations ([Cl−]i; [Ca2+]i) in porcine aortic endothelial cells. Methods: Using the fluorescent probes N-ethoxycarbonylmethyl-6-methoxyquinolinium bromide (MQAE) and fura-2/AM, the effects of different MLCK inhibitors on bradykinin- and thapsigargin-induced changes in [Cl−]i and [Ca2+]i were assessed. Results: Bradykinin and thapsigargin significantly decreased the MQAE fluorescence intensity, which indicates increased [Cl−]i; these changes were reversed by removal of extracellular chloride (Cl−o) and were significantly inhibited by Cl−-channel inhibitor N-phenylanthranilic acid but not by Na+–K+–Cl− cotransport inhibitor furosemide. Pretreatment with ML-9 and wortmannin, two different selective inhibitors of MLCK, significantly reduced these changes in a dose-dependent manner. The inhibitory effects of ML-9 and wortmannin on the Cl− responses were not significantly different and were not additive. Bradykinin and thapsigargin provoked large increases in [Ca2+]i, which were significantly diminished by removal of Cl−o and by pretreatment with the Cl−-channel inhibitor N-phenylanthranilic acid. Conclusions: The study shows that an increase in [Cl−]i may be involved in the Ca2+ influx in response to bradykinin and thapsigargin and that MLCK might be involved in the Cl− response. We suggest that MLCK might be involved in the Cl−-sensitive endothelial Ca2+ responses to bradykinin and thapsigargin.
Disrupted Brain Circuitry for Pain‐Related Reward/Punishment in Fibromyalgia
Authors: Marco L. Loggia, Chantal Berna, Jieun Kim, Christine M. Cahalan, Randy L. Gollub, Ajay D. Wasan, Richard E. Harris, Robert R. Edwards, Vitaly Napadow
Journal: Arthritis & Rheumatology (2013)

Objective While patients with fibromyalgia (FM) are known to exhibit hyperalgesia, the central mechanisms contributing to this altered pain processing are not fully understood. This study was undertaken to investigate potential dysregulation of the neural circuitry underlying cognitive and hedonic aspects of the subjective experience of pain, such as anticipation of pain and anticipation of pain relief. Methods Thirty‐one FM patients and 14 controls underwent functional magnetic resonance imaging, while receiving cuff pressure pain stimuli on the leg calibrated to elicit a pain rating of ∼50 on a 100‐point scale. During the scan, subjects also received visual cues informing them of the impending onset of pain (pain anticipation) and the impending offset of pain (relief anticipation). Results Patients exhibited less robust activation during both anticipation of pain and anticipation of relief within regions of the brain commonly thought to be involved in sensory, affective, cognitive, and pain‐modulatory processes. In healthy controls, direct searches and region‐of‐interest analyses of the ventral tegmental area revealed a pattern of activity compatible with the encoding of punishment signals: activation during anticipation of pain and pain stimulation, but deactivation during anticipation of pain relief. In FM patients, however, activity in the ventral tegmental area during periods of pain and periods of anticipation (of both pain and relief) was dramatically reduced or abolished. Conclusion FM patients exhibit disrupted brain responses to reward/punishment. The ventral tegmental area is a source of reward‐linked dopaminergic/γ‐aminobutyric acid–releasing (GABAergic) neurotransmission in the brain, and our observations are compatible with reports of altered dopaminergic/GABAergic neurotransmission in FM. Reduced reward/punishment signaling in FM may be related to the augmented central processing of pain and reduced efficacy of opioid treatments in these patients.
Calibration and discriminatory accuracy of prognosis calculation for breast cancer with the online Adjuvant! program: a hospital-based retrospective cohort study
Authors: Stella Mook, Marjanka K Schmidt, Emiel J Rutgers, Anthonie O van de Velde, Otto Visser, Sterre M Rutgers, Nicola Armstrong, Laura J van't Veer, Peter M Ravdin
Journal: The Lancet Oncology (2009)
Reversal of the Malignant Phenotype of Gastric Cancer Cells by Inhibition of RhoA Expression and Activity
Authors: Na Liu, Feng Bi, Yanglin Pan, Lijun Sun, Yan Xue, Yongquan Shi, Xuebiao Yao, Yi Zheng, Daiming Fan
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The small GTPase RhoA has been implicated in the regulation of cell morphology, motility, and transformation, but the role of RhoA protein in the carcinogenesis of gastric cancer remains unclear. In the present study, we have analyzed the expression status of the RhoA protein in human gastric cancer cells and tissues and investigated the possible involvement of RhoA in regulating the malignant phenotype of gastric cancer cells. Experimental Design: RhoA expression was analyzed by immunohistochemistry and Western blot in gastric cancer tissues and cell lines. The RhoA-specific small interfering RNA (siRNA) vector was designed and constructed. We examined the role of RhoA in the malignant phenotype of gastric cancer cells by using siRNA knockdown and dominant-negative RhoA mutant suppression of endogenous RhoA activity. Results: RhoA was found frequently overexpressed in gastric cancer tissues and cells compared with normal tissues or gastric epithelial cells. RhoA-specific siRNA could specifically and stably reduce RhoA expression up to 90% in AGS cells. Both RhoA-specific siRNA and dominant-negative RhoA expressions could significantly inhibit the proliferation and tumorigenicity of AGS cells and enhance chemosensitivity of the cancer cells to Adriamycin and 5-fluorouracil. Conclusion: RhoA may play a critical role in the carcinogenesis of gastric cancer, and the interference of RhoA expression and/or activity could provide a novel avenue in reversing the malignant phenotype of gastric cancer cells.
Predicting Evolutionary Potential. I. Predicting the Evolution of a Lactose-PTS System in Escherichia coli
Authors: Barry G. Hall
Journal: Molecular Biology and Evolution (2001)

Genomes contain not only information for current biological functions, but also information for potential novel functions that may allow the host to adapt to new environments. The field of experimental evolution studies that potential by selecting for novel functions and deducing the means by which the function evolved, but until now it has not attempted to predict the outcomes of such experiments. Here I present a model system that is being developed specifically to examine the issue of what kind of information is most useful in predicting how novel functions will evolve. The system is the evolution of a Lac-PTS transport system and a phospho-β-galactosidase hydrolase system as a novel pathway for metabolism of lactose in Escherichia coli. Two kinds of information, sequence-based phylogenetic inference and biochemical activity, are considered as predictors of which E. coli genes will evolve the required new functions. Both biochemical data and phylogenetic inference predict that the cryptic celABC genes, which currently specify a PTS-β-glucoside transport system, are most likely to evolve into a PTS-lactose transport system. Phylogenetic inference predicts that the bglA gene, which currently specifies a phospho-β-glucosidase, is most likely to evolve into a phospho-β-galactosidase. In contrast, biochemical data predict that the cryptic bglB gene, which also currently specifies a phospho-β-glucosidase, is most likely to evolve into a phospho-β-galactosidase.
Pulmonary surfactant: a front line of lung host defense
Authors: Jo Rae Wright
Journal: Journal of Clinical Investigation (2003)

The lung is a uniquely vulnerable organ. Residing at the interface of the body and the environment, the lung is optimized for gas exchange, having a very thin, delicate epithelium, abundant blood flow, and a vast surface area. Inherent in this structure is an enormous immunological burden from pathogens, allergens, and pollutants resident in the 11,000 liters of air inhaled daily. Fortunately, protective immune mechanisms act locally in the lung to facilitate clearance of inhaled pathogens and to modulate inflammatory responses. These defensive mechanisms include both innate (nonantibody-mediated) and adaptive (antibody-mediated) systems. The purpose of this commentary is to review briefly the functions of one unique lung innate immune system, pulmonary surfactant, and to highlight the recent findings of Wu et al. (1) described in this issue of the JCI. Wu and colleagues report a new and intriguing innate immune function of surfactant: direct antimicrobial activity.
Choose and book—whose choice is it anyway?
Authors: Nigel de Kare-Silver
Journal: BMJ (2005)

L ast summer I took part in many of the workshops held across London for the NHS's national programme for information technology. Organised with little notice and undergoing continual cancellation, rescheduling, and relocation, many of the sessions somehow resulted in vibrant discussions with clear conclusions. The people who went were keen, if not passionate, to do what they could to make sure the outcome would be the best possible. We were unanimous in wanting to make sure that the NHS offered programs that used the best possible features of existing software and clinical practice and that offered clinicians and patients a signed pathway to the best possible care. We were clearly told by the session leaders from British Telecom and IDX, the companies involved, that their contract was to design and supply clinical software to be used universally across the NHS.

What did we get when we were presented with the draft version? We were shown screens of a third rate computer program …
Identification of Linguistic Barriers to Diabetes Knowledge and Glycemic Control in Chinese Americans With Diabetes
Authors: William C. Hsu, Sophia Cheung, Emmelyn Ong, Kathy Wong, Susan Lin, Kenneth Leon, Katie Weinger, George L. King
Journal: Diabetes Care (2006)

he Asian-American population, a fast-growing minority group in America (1), is more likely to have type 2 diabetes compared with non-Hispanic whites despite having lower body weight (2-6).Among the diverse Asian immigrants, Chinese Americans make up the largest subgroup (1), of whom 50% live in linguistic isolation (7).Communication problems with health care providers (8) and the lack of culturally appropriate diabetes education (9), among other factors (10,11), may be important contributors to disparities in health (12-15) and diabetes control ( 16) in Chinese Americans.In this study, we identified linguistic barriers to diabetes education and care in Chinese Americans and explored the appropriate venues to deliver diabetes information to Chinese-American communities. RESEARCH DESIGN AND METHODS -Subjects were ethnicChinese residing in the U.S. Participants (aged 18 -70 years) had diabetes for at least 1 year and were taking oral agents and/or insulin.All volunteers can read, write, and speak at least English, Mandarin, or Cantonese.We recruited participants from local Asian community health centers in Boston, New York, New Jersey, and San Francisco, using fliers posted in the clinics, advertisements in local Chinese newspapers, mailings to patients from these clinics, and announcements during community outreach.Volunteers received monetary compensation and a