tbuckley/cabot-search huggingface dataset:
Limited therapeutic efficacy of pioglitazone on progression of hepatic fibrosis in rats
Authors: I A Leclercq
Journal: Gut (2006)

<b>Aim:</b> Peroxisome proliferator activated receptor γ (PPARγ) agonists have been shown to prevent hepatic fibrosis in rodents. We evaluated the therapeutic antifibrotic potential of the PPARγ agonist pioglitazone on established hepatic fibrosis. <b>Methods:</b> Repeated injections of carbon tetrachloride (CCl<sub>4</sub>), a choline deficient diet, or bile duct ligation (BDL) were used to induce hepatic fibrosis in rats. Pioglitazone treatment was introduced at various time points. Therapeutic efficacy was assessed by comparison of the severity of hepatic fibrosis in pioglitazone treated versus untreated fibrotic controls. <b>Results:</b> When introduced after two weeks of CCl<sub>4</sub>, pioglitazone reduced hepatic fibrosis, OH proline content, hepatic mRNA expression of collagen type I, and profibrotic genes, as well as the number of activated α smooth muscle actin positive hepatic stellate cells, compared with rats receiving CCl<sub>4</sub> only, with no significant change in necroinflammation. When pioglitazone treatment was initiated after five weeks of CCl<sub>4</sub>, no antifibrotic effect was observed. Similarly, pioglitazone was associated with a reduced severity of fibrosis induced by a choline deficient diet when introduced early, while delayed treatment with pioglitazone remained ineffective. In contrast, pioglitazone failed to interrupt progression of fibrosis due to BDL, irrespective of the timing of its administration. <b>Conclusion:</b> In rats, the therapeutic antifibrotic efficacy of pioglitazone is limited and dependent on the type of injury, duration of disease, and/or the severity of fibrosis at the time of initiation of treatment.
Mcl-1 expression has in vitro and in vivo significance in chronic lymphocytic leukemia and is associated with other poor prognostic markers
Authors: Chris Pepper, Thet Thet Lin, Guy Pratt, Saman Hewamana, Paul Brennan, Louise Hiller, Robert Hills, Rachel Ward, Jane Starczynski, Belinda Austen, Laura Hooper, Tatjana Stankovic, Chris Fegan
Journal: Blood (2008)
Maternal exposure to <scp>GOS</scp>/inulin mixture prevents food allergies and promotes tolerance in offspring in mice
Authors: G. Bouchaud, L. Castan, J. Chesné, F. Braza, P. Aubert, M. Neunlist, A. Magnan, M. Bodinier
Journal: Allergy (2015)

Abstract Background Food allergies affect 4–8% of children and are constantly on the rise, thus making allergies a timely issue. Most importantly, prevention strategies are nonexistent, and current therapeutic strategies have limited efficacy and need to be improved. One alternative to prevent or reduce allergies, particularly during infancy, could consist of modulating maternal immunity and microbiota using nondigestible food ingredients, such as prebiotics. For this purpose, we studied the preventive effects of prebiotics in Balb/c mothers during pregnancy and breastfeeding on food allergy development in offspring mice. Methods After weaning, the offspring from mothers that were exposed to GOS /inulin mixture or fed a control diet were intraperitoneally sensitized to wheat proteins to induce a systemic allergic response and orally exposed to the same allergen. Immunological, physiological, and microbial parameters were analyzed. Results GOS /inulin mixture diet modified the microbiota of mothers and their offspring. Offspring from mothers that received GOS /inulin prebiotics were protected against food allergies and displayed lower clinical scores, specifically of IgE and histamine levels, compared to offspring from mothers fed a control diet. Moreover, GOS /inulin supplementation for the mother resulted in stronger intestinal permeability in the offspring. Enhancement of the regulatory response to allergic inflammation and changes in the Th2/Th1 balance toward a dampened Th2 response were observed in mice from GOS /inulin mixture‐exposed mothers. Conclusion The treatment of pregnant and lactating mice with nondigestible GOS /inulin prebiotics promotes a long‐term protective effect against food allergies in the offspring.
Genetic alterations in the gene encoding the major HBsAg: DNA and immunological analysis of recurrent HBsAg derived from monoclonal antibody—treated liver transplant patients
Authors: Gerald McMahon, Paul H. Ehrlich, Zeinab A. Moustafa, Linda A. McCarthy, Diane Dottavio, Mark D. Tolpin, Paul I. Nadler, Lars Östberg
Journal: Hepatology (1992)

A gene region encoding a segment of the major surface protein, HBsAg, of hepatitis B virus was analyzed from serum samples after orthotopic liver transplantation of three hepatitis B virus chronic carrier patients treated with a human anti-hepatitis B virus monoclonal antibody (SDZ OST 577). Each of these three patients became HBsAg negative after transplantation and therapy with the human anti-hepatitis B virus monoclonal antibody but returned to HBsAg positivity (first detected 143,251 and 252 days after the transplantation). Polymerase chain reaction DNA amplification was performed on DNA from serum samples showing low levels of recurrent HBsAg and reduced antigen reactivity with SDZ OST 577 antibody. Polymerase chain reaction DNA included a 230-bp highly conserved, major S gene region that was cloned into M13 bacteriophage; analysis of this DNA segment provided a consensus of DNA sequences for the serum samples exhibiting altered reactivity with the therapeutic monoclonal. Analysis of independent DNA clones from serum samples of patients exhibiting low but detectable recurrent serum levels of posttherapy HBsAg revealed the presence of S protein variant sequences when compared with polymerase chain reaction DNA derived from the original infected liver or pretherapy serum HBsAg. Genetic variation was predominant in a highly conserved peptide domain that has previously been implicated in antibody binding and neutralizing antibody epitopes. In independent patients infected with either adw or ayw hepatitis B virus subtypes, single nucleotide changes resulted in one to two amino acid differences for each variant allele (residues 124, 129, 131, 137, 140 and/or 145) when compared with pretherapy viral DNA. Administration of serum containing one of these variant viruses to a single hepatitis B-naive chimpanzee resulted in subclinical hepatitis and detectable levels of circulating anti-HBs and anti-HBc antibodies 49 and 70 days after virus administration, respectively. Hepatitis B virus DNA was recovered on liver biopsy between 6 and 8 wk after inoculation, although the animal remained persistently seronegative for HBsAg. DNA sequence analysis of both primate and patient liver hepatitis B virus confirmed the presence of the DNA encoding the S protein variant and associates this DNA with the predominant hepatotropic virus in liver infection.
Preoperative chemotherapy in advanced resectable OCSCC: long-term results of a randomized phase III trial
Authors: P. Bossi, S. Lo Vullo, M. Guzzo, L. Mariani, R. Granata, E. Orlandi, L. Locati, G. Scaramellini, C. Fallai, L. Licitra
Journal: Annals of Oncology (2014)
Testing for Gestational Diabetes Mellitus in Australia
Authors: Alison Nankervis, Harold David McIntyre, Robert G. Moses, Glynis P. Ross, Leonie K. Callaway
Journal: Diabetes Care (2013)

The American Diabetes Association published new recommendations for the detection and diagnosis of gestational diabetes mellitus in 2011 (1). These criteria were based on the consensus opinion of the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) (2). The Australasian Diabetes in Pregnancy Society (ADIPS) has posted new guidelines (www.adips.org) to replace those used since 1991 (3).

The ADIPS guidelines endorse the method of testing and the diagnostic criteria used by the American Diabetes Association. These are early testing for women with high risk factors; no preliminary glucose challenge test; and for all women not known to have diabetes, a 75-g oral glucose tolerance test at 24–28 weeks’ gestation, with gestational diabetes mellitus diagnosed if one of …
Estrogen-Receptor Polymorphisms and Effects of Estrogen Replacement on High-Density Lipoprotein Cholesterol in Women with Coronary Disease
Authors: David M. Herrington, Timothy D. Howard, Gregory A. Hawkins, David M. Reboussin, Jianfeng Xu, Siqun L. Zheng, K. Bridget Brosnihan, Deborah A. Meyers, Eugene R. Bleecker
Journal: New England Journal of Medicine (2002)

Sequence variants in the gene encoding estrogen receptor α (ER-α) may modify the effects of hormone-replacement therapy on levels of high-density lipoprotein (HDL) cholesterol and other outcomes related to estrogen treatment in postmenopausal women.
Epidemic outbreak of interstitial lung disease in aerographics textile workers--the "Ardystil syndrome": a first year follow up.
Authors: A. Sole, P. J. Cordero, P. Morales, M. E. Martinez, F. Vera, C. Moya
Journal: Thorax (1996)

The longer term respiratory effects of massive inhalational exposure of textile printing sprayers to Acramin (the "Ardystil syndrome") are not well established.A 12 month follow up of 27 heavily exposed textile sprayers was performed.Twenty one patients experienced cough, 18 dyspnoea, and 17 nose bleeding at initial exposure, with histological evidence of organising pneumonia in 13 cases, radiological abnormalities detected by computed tomographic scanning in 20 cases, and diminution of diffusion capacity to below 80% of predicted in seven cases. At one year after exposure symptoms persisted in 15 cases, radiological alterations in six, and diffusion capacity was reduced in nine.Whilst most of our patients showed improvement at one year, evidence of persistent lung involvement was present in an appreciable minority of exposed cases.
Targeted Disruption of Kir2.1 and Kir2.2 Genes Reveals the Essential Role of the Inwardly Rectifying K <sup>+</sup> Current in K <sup>+</sup> -Mediated Vasodilation
Authors: Joshua J. Zaritsky, Delrae M. Eckman, George C. Wellman, Mark T. Nelson, Thomas L. Schwarz
Journal: Circulation Research (2000)

Abstract —The molecular bases of inwardly rectifying K + (Kir) currents and K + -induced dilations were examined in cerebral arteries of mice that lack the Kir2.1 and Kir2.2 genes. The complete absence of the open reading frame in animals homozygous for the targeted allele was confirmed. Kir2.1 −/− animals die 8 to 12 hours after birth, apparently due to a complete cleft of the secondary palate. In contrast, Kir2.2 −/− animals are viable and fertile. Kir currents were observed in cerebral artery myocytes isolated from control neonatal animals but were absent in myocytes from Kir2.1 −/− animals. Voltage-dependent K + currents were similar in cells from neonatal control and Kir2.1 −/− animals. An increase in the extracellular K + concentration from 6 to 15 mmol/L caused Ba 2+ -sensitive dilations in pressurized cerebral arteries from control and Kir2.2 mice. In contrast, arteries from Kir2.1 −/− animals did not dilate when the extracellular K + concentration was increased to 15 mmol/L. In summary, Kir2.1 gene expression in arterial smooth muscle is required for Kir currents and K + -induced dilations in cerebral arteries. (Circ Res. 2000;87:160-166.)
LSC 2013 abstract - ST13 and ORMDL3 polymorphisms affect the risk of exacerbations in steroid-treated asthmatic children and young adults
Authors: Susanne Vijverberg, Ellen Koster, Roger Tavendale, Maarten Leusink, Leo Koenderman, Jan Raaijmakers, Dirkje Postma, Gerard Koppelman, Steve Turner, Somnath Mukhopadhyay, Sze Man Tse, Kelan Tantisira, Colin Palmer, Anke-Hilse Maitland-van der Zee
Journal: European Respiratory Journal (2013)

Background:  Genetic variation has been associated with altered corticosteroid response in asthmatic patients.   Aim:  To study whether variation in 17 candidate genes is associated with exacerbations in asthmatic children and adolescents treated with inhaled corticosteroids (ICS).   Material and methods:  We performed a meta-analysis of 4 studies: the PACMAN study (n=357, age: 4-12, NL), the BREATHE study (n=818, age: 3-22, UK), the PAGES study (n=391, age: 2-16, UK) and the CAMP trial (n=172, age: 5-12, USA). Genes were selected based on their role in the glucocorticoid signaling pathway or a previously reported association with asthma. Fifty SNPs were screened. As outcomes we studied: 1) asthma-related hospital visits, 2) oral corticosteroid (OCS) use in the previous year. Odds ratios (OR) were corrected for age, sex and treatment step and meta-analyzed assuming random effects with the inverse variance weighting method. Q-values were calculated to correct for multiple testing.   Results:  We found two SNPs in ST13 to be associated with both outcomes. ST13 rs138335 C-allele was associated with a decreased risk of exacerbations (OCS use OR: 0.78, 95%CI:0.65-0.91, p=0.003, q=0.05; hospital visits OR: 0.78, 95%CI: 0.63-0.97, p=0.02, q=0.45). The G-allele of rs138337 ST13 was associated with an increased risk (OCS use OR:1.18, 95%CI:1.01-1.38, p=0.03, q=0.31; hospital visits OR: 1.30, 95%CI:1.07-1.58, p=0.007, q=0.28). Furthermore, the C-allele of rs7216389 ORMDL3 was associated with fewer OCS use in the previous year (OR: 0.77, 95%CI:0.62-0.95, p=0.02, q=0.05).   Conclusion:  ST13 and ORMDL3 seem to be associated with altered risk of asthma exacerbations despite ICS treatment.
Poliomyelitis outbreak in Israel in 1988: a report with two commentaries
Authors: P.E. Slater, C. Costin, A. Yarrow, T. Ben-Zvi, A. Avni, I. Epstein, W.A. Orenstein, A. Morag, R. Handsher, M.S. Green, S. Rishpon, O. Havkin, T.A. Swartz, O.M. Kew, M. Rey, J.L. Melnick
Journal: The Lancet (1990)
An Erythroid Differentiation Signature Predicts Response to Lenalidomide in Myelodysplastic Syndrome
Authors: Benjamin L Ebert, Naomi Galili, Pablo Tamayo, Jocelyn Bosco, Raymond Mak, Jennifer Pretz, Shyam Tanguturi, Christine Ladd-Acosta, Richard Stone, Todd R Golub, Azra Raza
Journal: PLoS Medicine (2008)

Lenalidomide is an effective new agent for the treatment of patients with myelodysplastic syndrome (MDS), an acquired hematopoietic disorder characterized by ineffective blood cell production and a predisposition to the development of leukemia. Patients with an interstitial deletion of Chromosome 5q have a high rate of response to lenalidomide, but most MDS patients lack this deletion. Approximately 25% of patients without 5q deletions also benefit from lenalidomide therapy, but response in these patients cannot be predicted by any currently available diagnostic assays. The aim of this study was to develop a method to predict lenalidomide response in order to avoid unnecessary toxicity in patients unlikely to benefit from treatment.
Studies on infant diarrhea. I. A comparison of the effects of milk feeding and intravenous therapy upon the composition and volume of the stool and urine.
Authors: R Torres-Pinedo, M Lavastida, C L Rivera, H Rodrïguez, A Ortiz
Journal: Journal of Clinical Investigation (1966)

This study reproduced in a group of infants with acute diarrhea the conditions under which systemic acidosis usually ensues in infantile diarrheal disease.  These conditions were achieved in order to assess changes in stool composition and the influence of milk intake on the composition of the stools and on the acid-base equilibrium; these changes were compared with similar observations during fasting and intravenous therapy.  Also specific challenges with individual sugars were done in some patients and the changes induced in stool composition were studied.  9 infants were studied during consecutive periods of milk feeding and intravenous therapy.  During milk administration the stools were abundant and markedly acidic and contained large quantities of lactate and other organic acids of low pKa.  With fasting all parameters decreased significantly.  When sugar loads were administered orally increased fecal excretion of carbohydrate occurred along with compositional changes qualitatively identical to those observed after milk ingestion.  It is concluded that the high lactate content and high content of other inorganic anions in diarrheal stools in infants are related to carbohydrate ingestion.  Therefore increased fecal excretion of endogenously produced organic acid anions in their neutralized dissociated form probably has a role in the genesis of the metabolic acidosis found in diarrhea.
Efficacy and Safety of Dabigatran Etexilate and Warfarin in “Real-World” Patients With Atrial Fibrillation
Authors: Torben Bjerregaard Larsen, Lars Hvilsted Rasmussen, Flemming Skjøth, Karen Margrete Due, Torbjörn Callréus, Mary Rosenzweig, Gregory Y.H. Lip
Journal: Journal of the American College of Cardiology (2013)
Surfactant protein A and other bronchoalveolar lavage fluid proteins are altered in cystic fibrosis
Authors: C. von Bredow, P. Birrer, M. Griese
Journal: European Respiratory Journal (2001)

Inflammation and proteolytic processes play an important role in the progression of cystic fibrosis (CF) lung disease. The goal of this study was to describe bronchoalveolar lavage fluid (BALF) protein pattern of CF patients in comparison to controls and to assess if there is proteolytic degradation of surfactant protein A (SP-A), an important innate host defence component of the lungs. BALFs from 17 clinically stable CF patients and from eight healthy children were separated by two-dimensional gel electrophoresis. Silver staining was used to show BALF proteins and Western blotting to detect SP-A isoforms. In CF, BALF proteins of a low molecular weight ≤20 kD were more abundant than in controls. Various proteins were seen in CF which were not present in controls and vice versa . Degradation of SP-A was present in 15 of 17 CF BALFs but in none of the controls, in contrast polymeric isoforms were seen in all controls and in four of 17 CF patients. Proteolytic damage to surfactant protein A and significant changes of normal bronchoalveolar lavage fluid proteins occur in lungs of cystic fibrosis patients. Identification of altered bronchoalveolar lavage fluid proteins may give new insights into pathogenic mechanisms and provide new targets for therapy.
Immunohistochemical Detection of HER1/HER2 Can Be Considered a Predictive Marker of Gefitinib Activity in Non-Small-Cell Lung Cancer?
Authors: Cristina Noberasco, Tommaso De Pas, Giuseppe Curigliano, Sara Manzoni, Lucia Dodaro, Giuseppe Pelosi, Lorenzo Spaggiari, Filippo De Braud
Journal: Journal of Clinical Oncology (2005)
Predicting Drug Targets and Biomarkers of Cancer via Genome-Scale Metabolic Modeling
Authors: Livnat Jerby, Eytan Ruppin
Journal: Clinical Cancer Research (2012)

Abstract The metabolism of cancer cells is reprogrammed in various ways to support their growth and survival. Studying these phenomena to develop noninvasive diagnostic tools and selective treatments is a promising avenue. Metabolic modeling has recently emerged as a new way to study human metabolism in a systematic, genome-scale manner by using pertinent high-throughput omics data. This method has been shown in various studies to provide fairly accurate estimates of the metabolic phenotype and its modifications following genetic and environmental perturbations. Here, we provide an overview of genome-scale metabolic modeling and its current use to model human metabolism in health and disease. We then describe the initial steps made using it to study cancer metabolism and how it may be harnessed to enhance ongoing experimental efforts to identify drug targets and biomarkers for cancer in a rationale-based manner. Clin Cancer Res; 18(20); 5572–84. ©2012 AACR.
Stability of Phosphoprotein as a Biological Marker of Tumor Signaling
Authors: Amanda F. Baker, Tomislav Dragovich, Nathan T. Ihle, Ryan Williams, Cecilia Fenoglio-Preiser, Garth Powis
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The purpose of the study was to evaluate the stability of phosphoprotein as a marker of signaling activity in human tumors using clinical samples and xenografts. Experimental Design: The expression of phospho-Ser473-Akt (p-Akt) was assessed by immunohistochemistry in paraffin-embedded samples from patients enrolled in a Southwest Oncology Group clinical trial of gastroesophageal junction tumors and by immunohistochemistry and Western blotting in human colon tumor xenografts at various times after removal from the animal. Results: Clinical samples had evaluable p-Akt staining only when obtained as biopsies (9 of 13) and no staining was observed in tumors obtained as surgically resected samples (0 of 15). In HT-29 colon cancer xenografts, p-Akt staining was present in fresh sample but not in tissue that had been allowed to stand for 30 minutes at room temperature. Western blotting of HT-29 tumor xenografts at room temperature showed a slow decrease in total Akt with a half-life of 180 minutes and a rapid decrease in p-Akt with a half-life of 20 minutes. Conclusions: Caution should be used when using phosphoprotein levels in human tumor specimens to measure intrinsic signaling activity or drug effects because of the potential for rapid dephosphorylation. Rapid processing of biopsies is essential and postoperative surgical samples may be of limited value because of the time to fixation.
Cbln1 is essential for synaptic integrity and plasticity in the cerebellum
Authors: Hirokazu Hirai, Zhen Pang, Dashi Bao, Taisuke Miyazaki, Leyi Li, Eriko Miura, Jennifer Parris, Yongqi Rong, Masahiko Watanabe, Michisuke Yuzaki, James I Morgan
Journal: Nature Neuroscience (2005)
Heat Shock Protein 27 Differentiates Tolerogenic Macrophages That May Support Human Breast Cancer Progression
Authors: Sanjib Banerjee, Chuen-Fu L. Lin, Kristin A. Skinner, Linda M. Schiffhauer, James Peacock, David G. Hicks, Eileen M. Redmond, David Morrow, Alissa Huston, Michelle Shayne, Howard N. Langstein, Carol L. Miller-Graziano, Jennifer Strickland, Lauren O'Donoghue, Asit K. De
Journal: Cancer Research (2011)

Abstract Tumor cells release several factors that can help the progression of the tumor by directly supporting tumor growth and/or suppressing host antitumor immunity. Here, we report that human primary breast tumor cells not only express elevated levels of heat shock protein 27 (Hsp27) at the intracellular level but also release extremely high levels of Hsp27 compared with the same patients' serum Hsp27 levels, predicting an acutely increased concentration of soluble Hsp27 in the human breast tumor microenvironment (HBTM). We demonstrate that Hsp27 levels in the HBTM can be extremely elevated as evidenced by high soluble Hsp27 levels in patients' tumor interstitial fluid. Because increasing numbers of tumor-associated macrophages (TAM) in the HBTM negatively correlate to patients' clinical outcomes and we have previously reported the immunoregulatory activity of soluble Hsp27, here, we tested for any specific effects of soluble Hsp27 on human monocyte to macrophage differentiation. We demonstrate that soluble Hsp27 causes the differentiation of monocytes to macrophages with immuno-tolerizing phenotypes (HLA-DRlow, CD86low, PD-L1high, ILT2high, and ILT4high). We detected the presence of TAMs with similar phenotypes in breast cancer patients. Hsp27-differentiated macrophages induce severe unresponsiveness/anergy in T cells. Moreover, these macrophages lose tumoricidal activity but become extremely proangiogenic, inducing significant neovascularization, a process that is critically important for tumor growth. Thus, our data demonstrate a novel immune escape and tumor growth–supporting mechanism mediated by soluble Hsp27 that may be operative in human breast cancer. Cancer Res; 71(2); 318–27. ©2011 AACR.
Vivax malaria resistant to treatment and prophylaxis with chloroquine
Authors: G.S. Murphy, H. Basri, E.M. Andersen, M.J. Bangs, J. Gorden, K. Sorensen, D.L. Mount, A.A. Lal, A.R. Purwokusumo, S. Harjosuwarno, S.L. Hoffman
Journal: The Lancet (1993)