tbuckley/cabot-search huggingface dataset:
Regulation of Apoptosis in Myeloid Cells by Interferon Consensus Sequence–Binding Protein
Authors: Lucia Gabriele, Jan Phung, Jon Fukumoto, David Segal, I-Ming Wang, Paraskevi Giannakakou, Nathalie A. Giese, Keiko Ozato, Herbert C. Morse
Journal: The Journal of Experimental Medicine (1999)

Mice with a null mutation of the gene encoding interferon consensus sequence-binding protein (ICSBP) develop a disease with marked expansion of granulocytes and macrophages that frequently progresses to a fatal blast crisis, thus resembling human chronic myelogenous leukemia (CML). One important feature of CML is decreased responsiveness of myeloid cells to apoptotic stimuli. Here we show that myeloid cells from mice deficient in ICSBP exhibit reduced spontaneous apoptosis and a significant decrease in sensitivity to apoptosis induced by DNA damage. In contrast, apoptosis in thymocytes from ICSBP-deficient mice is unaffected. We also show that overexpression of ICSBP in the human U937 monocytic cell line enhances the rate of spontaneous apoptosis and the sensitivity to apoptosis induced by etoposide, lipopolysaccharide plus ATP, or rapamycin. Programmed cell death induced by etoposide was specifically blocked by peptides inhibitory for the caspase-1 or caspase-3 subfamilies of caspases. Studies of proapoptotic genes showed that cells overexpressing ICSBP have enhanced expression of caspase-3 precursor protein. In addition, analyses of antiapoptotic genes showed that overexpression of ICSBP results in decreased expression of Bcl-X(L). These data suggest that ICSBP modulates survival of myeloid cells by regulating expression of apoptosis-related genes.
Increased Levels of Interleukin-6 Are Associated with Lymphocytosis in Bronchoalveolar Lavage Fluids of Idiopathic Nonspecific Interstitial Pneumonia
Authors: CHOON S. PARK, SUNG W. CHUNG, SHIN Y. KI, GUNE-IL LIM, SOO-TAEK UH, YONG H. KIM, DEUK I. CHOI, JAI S. PARK, DONG W. LEE, MASANORI KITAICHI
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Local overexpression of interleukin-6 (IL-6) experimentally induces lymphocytic infiltration in the bronchial tree of rat. Among idiopathic interstitial pneumonia (IIP), nonspecific interstitial pneumonia/fibrosis (NSIP) has an increased number of lymphocytes in bronchoalveolar lavage (BAL) fluid when compared with usual interstitial pneumonia (UIP). To reveal a relation of IL-6 with the lymphocyte infiltration of NSIP, IL-6 was measured in BAL fluids of idiopathic NSIP (n = 7), idiopathic UIP (n = 16), and normal control subjects (n = 45). IL-6-producing sites were assessed by IL-6 protein stain on biopsy specimens of NSIP, UIP, and normal lung of mediastinal tumors. Lymphocyte numbers and IL-6 levels in BAL fluids were higher in NSIP than those in UIP (p < 0.01, respectively), which were also higher when compared with those of normal control subjects (p < 0.01, respectively). In NSIP, the levels of IL-6 correlated with the number of lymphocytes (r = 0.93, p < 0.01). UIP cases were divided into two groups: high-UIP (n = 7) or low-UIP (n = 9) according to IL-6 levels greater than or within the 95 percentile of normal control subjects, respectively. The high-UIP group had BAL lymphocytosis when compared with the low-UIP group (p < 0.05). IL-6 stained on epithelial cells of the bronchial tree and on alveolar macrophages of NSIP and UIP. In conclusion, the lymphocytosis in BAL fluid of patients with NSIP and a subgroup of UIP is associated with the high levels of IL-6 and its sources are the epithelial cells of the small airway and the alveolar macrophages.
Hyperactivation of Stat3 in gp130 mutant mice promotes gastric hyperproliferation and desensitizes TGF-β signaling
Authors: Brendan J Jenkins, Dianne Grail, Thao Nheu, Meri Najdovska, Bo Wang, Paul Waring, Melissa Inglese, Rachel M McLoughlin, Simon A Jones, Nicholas Topley, Heinz Baumann, Louise M Judd, Andrew S Giraud, Alex Boussioutas, Hong-Jian Zhu, Matthias Ernst
Journal: Nature Medicine (2005)
Isolated Tumor Cells in Bone Marrow Three Years after Diagnosis in Disease-Free Breast Cancer Patients Predict Unfavorable Clinical Outcome1
Authors: Gro Wiedswang, Elin Borgen, Rolf Kåresen, Hanne Qvist, Jan Janbu, Gunnar Kvalheim, Jahn M. Nesland, Bjørn Naume
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The aim of the study was to explore the value of analyzing bone marrow (BM) for the presence of isolated tumor cell(s) (ITCs) in disease-free breast cancer patients 3 years after diagnosis. Experimental Design: ITCs in BM at operation was found to be an independent prognostic factor in 817 breast cancer patients. Among these, 356 disease-free patients were analyzed with a second BM after 3 years follow-up (median 40 months, SD 3 months, range 29–52). ITC was detected by immunocytochemistry with anticytokeratine antibodies (AE1/AE3). Results: The population consisted of 70% T1 and 72% node-negative patients. ITC in BM was detected in 15%. At a median of 25 months since the second BM aspiration (66 months since diagnosis), 32 patients had developed relapse, 12 local and 20 systemic. Of the patients with ITC in BM, 21% relapsed compared with 7% of the ITC-negative patients (P &amp;lt; 0.001). Ten patients died of breast cancer. Survival analyses showed that ITC in BM predicted reduced distant disease-free survival (DDFS) and breast cancer specific survival (BCSS; P &amp;lt; 0.001, log-rank test). Uni-and multivariate analyses of the prognostic value of N, T, estrogen receptor/progesterone receptor, and BM status, histological grade, vascular invasion, p53-, c-erb-B2-, and cathepsin D expression were performed. BM status was the only independent prognostic factor for both DDFS and BCSS, whereas c-erbB-2 and N status were independent for BCSS and vascular invasion and T status for DDFS. Conclusions: ITC in BM 3 years after diagnosis in disease-free breast cancer patients is an independent prognostic factor. Detection of residual disease by BM analysis at follow-up may unravel insufficient adjuvant treatment. The clinical implications should be further explored.
A Multigene Expression Assay to Predict Local Recurrence Risk for Ductal Carcinoma In Situ of the Breast
Authors: L. J. Solin, R. Gray, F. L. Baehner, S. M. Butler, L. L. Hughes, C. Yoshizawa, D. B. Cherbavaz, S. Shak, D. L. Page, G. W. Sledge, N. E. Davidson, J. N. Ingle, E. A. Perez, W. C. Wood, J. A. Sparano, S. Badve
Journal: JNCI Journal of the National Cancer Institute (2013)

BackgroundFor women with ductal carcinoma in situ (DCIS) of the breast, the risk of developing an ipsilateral breast event (IBE; defined as local recurrence of DCIS or invasive carcinoma) after surgical excision without radiation is not well defined by clinical and pathologic characteristics.
Determinants of Vascular Smooth Muscle Cell Apoptosis After Balloon Angioplasty Injury
Authors: Matthew J. Pollman, Jennifer L. Hall, Gary H. Gibbons
Journal: Circulation Research (1999)

Abstract —We have observed that acute medial cell loss is an initial event in the response to vascular injury induced by balloon-catheter distention of the rabbit carotid artery. Numerous apoptotic medial cells were observed as early as 30 minutes after balloon inflation, and a 70% loss of cellularity was evident by 90 minutes. Balloon injury was associated with oxidative stress as reflected by a fall in glutathione levels by 63% within 30 minutes after injury. We hypothesized that balloon injury activated a redox-sensitive signaling pathway coupled to the regulation of apoptosis. Indeed, the activity of the proapoptotic signal mediator, stress-activated protein kinase, was increased severalfold within 10 minutes after injury. Moreover, modifying the vascular redox state by the administration of 1 of 2 structurally dissimilar antioxidants, N -acetyl cysteine or pyrrolidine dithiocarbamate, markedly attenuated both stress-activated protein kinase activation and the induction of apoptosis at 30 minutes. We hypothesized further that the induction of vascular smooth muscle cell apoptosis is modulated by phenotype. In contrast to medial cells, we observed that neointimal cells were relatively resistant to apoptotic death induced by angioplasty injury. This resistance to balloon injury–induced death was associated with an upregulation of the antiapoptotic mediator bcl-x L . This study suggests that acute apoptotic cell death after vascular injury is a highly regulated process governed by cellular redox state and the relative expression of antiapoptotic genes. Angioplasty-induced vascular cell apoptosis may be an important determinant of vascular remodeling and restenosis.
Detection of <i>TIMP3</i> Promoter Hypermethylation in Salivary Rinse as an Independent Predictor of Local Recurrence-Free Survival in Head and Neck Cancer
Authors: Wenyue Sun, David Zaboli, Hao Wang, Yan Liu, Demetri Arnaoutakis, Tanbir Khan, Zubair Khan, Wayne M. Koch, Joseph A. Califano
Journal: Clinical Cancer Research (2012)

Abstract Purpose: To validate a panel of methylation-based salivary rinse biomarkers (P16, CCNA1, DCC, TIMP3, MGMT, DAPK, and MINT31) previously shown to be independently associated with poor overall survival and local recurrence in a larger, separate cohort of patients with head and neck squamous cell carcinoma (HNSCC). Experimental Design: One hundred ninety-seven patients were included. All pretreatment saliva DNA samples were evaluated for the methylation status of the gene promoters by quantitative methylation-specific PCR. The main outcome measures were overall survival, local recurrence-free survival, and disease-free survival. Results: In univariate analyses, the detection of hypermethylation of CCNA1, MGMT, and MINT31 was significantly associated with poor overall survival; the detection of hypermethylation of TIMP3 was significantly associated with local recurrence-free survival; and the detection of hypermethylation of MINT31 was significantly associated with poor disease-free survival. In multivariate analyses, detection of hypermethylation at any single marker was not predictive of overall survival in patients with HNSCC; detection of hypermethylation of TIMP3 in salivary rinse had an independent, significant association with local recurrence-free survival (HR = 2.51; 95% CI: 1.10–5.68); and none of the studied markers was significantly associated with disease-free survival. Conclusion: The detection of promoter hypermethylation of the seven genes in salivary rinse as an independent prognostic indicator of overall survival in patients with HNSCC was not validated. Detection of promoter hypermethylation of TIMP3 in pretreatment salivary rinse is independently associated with local recurrence-free survival in patients with HNSCC and may be a valuable salivary rinse biomarker for HNSCC recurrence. Clin Cancer Res; 18(4); 1082–91. ©2012 AACR.
B-1 and B-2 Cell–Derived Immunoglobulin M Antibodies Are Nonredundant Components of the Protective Response to Influenza Virus Infection
Authors: Nicole Baumgarth, Ometa C. Herman, Gina C. Jager, Lorena E. Brown, Leonore A. Herzenberg, Jianzhu Chen
Journal: The Journal of Experimental Medicine (2000)

We have studied the role of secreted immunoglobulin (Ig)M in protection from infection with influenza virus and delineated the relative contributions of B-1 versus B-2 cell–derived IgM in this process. Mice deficient in secreted IgM but capable of expressing surface IgM and secreting other Ig classes show significantly reduced virus clearance and survival rates compared with wild-type controls. Irradiation chimeras in which only either B-1 or B-2 cells lack the ability to secrete IgM show mortality rates similar to those of mice in which neither B-1 nor B-2 cells secrete IgM. Dependence on both sources of IgM for survival is partially explained by findings in allotype chimeras that broadly cross-reactive B-1 cell–derived natural IgM is present before infection, whereas virus strain–specific, B-2 cell–derived IgM appears only after infection. Furthermore, lack of IgM secreted from one or both sources significantly impairs the antiviral IgG response. Reconstitution of chimeras lacking B-1 cell–derived IgM only with IgM-containing serum from noninfected mice improved both survival rates and serum levels of virus-specific IgG. Thus, virus-induced IgM must be secreted in the presence of natural IgM for efficient induction of specific IgG and for immune protection, identifying B-1 and B-2 cell–derived IgM antibodies as nonredundant components of the antiviral response.
The Pharmacological Effects of Hymenoptera Venoms
Authors: R M Cavagnol
Journal: The Annual Review of Pharmacology and Toxicology (1977)

The Hymenoptera form one of the largest and most highly developed orders of the class Insecta. As members of the Arthropoda phylum, which contains about 85% of the known animal world, these invertebrates exhibit segmented bodies, jointed appendages, and hard exoskeletons. The female of various Hymenoptera have evolved modified ovipositors, capable of delivering a venom to adversaries. This venom is a complex mixture of biochemical compounds ranging from simple amines to complicated proteins and enzymes. Because of their painful and sometimes fatal reactions in humans, Hymenoptera venoms are of interest to the clinician and researcher. The terms venom and poison were used interchangeably in early writings. The word venom is thought to have originated from the Latin veneneum, meaning a magical charm relating to Venus (2). A poison was originally a harmless draught or drink, the term probably derived from the Greek poloS (3). From POIOS evolved the Latin potum, to drink, and possibly potion, potable, and even pot, a vessel from which to drink. The fatal meaning of poison came about as a result of the ancient practice of giving a lethal potion, or drink, to one's enemies.
Obesity. Workshop III. AHA Prevention Conference III. Behavior change and compliance: keys to improving cardiovascular health.
Authors: S T St Jeor, K D Brownell, R L Atkinson, C Bouchard, J Dwyer, J P Foreyt, D Heber, P Kris-Etherton, J S Stern, W Willett
Journal: Circulation (1993)

The workshop provided the opportunity to discuss issues and develop and integrate ideas. The following recommendations for public policies, education programs, and high-priority research initiatives were developed: Recommendations for Public Policies: Focus on prevention by requiring school programs to emphasize appropriate diet, physical activity, and general health guidance to promote cardiovascular health and prevent disease through federal funding. Provide better access to exercise (city planning, work-site interventions). Influence food availability and accessibility. Influence reimbursement policies for effective early intervention and prevention strategies for obesity. Reevaluate policies for use of drugs in the treatment of obesity. Recommendations for Education Programs: Sponsor scientific workshop to: Define the most appropriate weight standards for prevention and treatment. Identify who should lose weight and why, when, and how. Promote the fact that obesity is an important health risk factor, even at moderate levels, and that excess visceral fat is particularly hazardous. Target health care professionals, consumers, and the media for education about: Nature of obesity as a heterogeneous syndrome. Recommendations for diet, exercise, behavioral interventions, drugs, and surgery. Recognition of special needs of populations of different ethnicity, gender, age, etc. State-of-the-art treatment and treatment programs. High-Priority Research Initiatives: Build better bridges between basic research and treatment/prevention practices. Acknowledge that obesity is a heterogeneous syndrome that may best be characterized as different obesities. Research on defining subtypes. Implications for etiology and treatment. Better characterization of genotypes and phenotypes. Study the effects of weight loss, weight gain,and weight cycling on medical and psychosocial outcomes and mortality.(ABSTRACT TRUNCATED AT 250 WORDS)
Life expectancy of adult liver allograft recipients in the UK
Authors: K Barber, J Blackwell, D Collett, J Neuberger
Journal: Gut (2006)

<b>Background:</b> Liver transplantation is a very successful therapy for those with end stage disease. Although there are numerous data on patient and graft survival after liver transplantation, life expectancy and possible loss of life (compared with a normal matched population) in those who survive remains unknown. <b>Aims:</b> To assess the life expectancy and life years lost of adult liver allograft recipients, compared with an age and sex matched UK population to provide patients with more information and to improve the use of a scarce resource. <b>Methods:</b> Using the National Transplant Database held by UK Transplant, on over 3600 adult liver allograft recipients transplanted between 1985 and 2003, we analysed survival of all adults who survived more than six months after transplantation and compared survival after transplantation with national age and sex matched controls to assess life years lost. <b>Results:</b> Estimated median survival time of the analysis cohort of 2702 adult liver allograft recipients was 22.2 years (95% confidence interval 19.3–25.6), with an estimated loss of seven life years compared with an age and sex matched population. <b>Conclusions:</b> Overall, female recipients have a longer life expectancy and lose fewer life years than male recipients. While younger recipients have a longer life expectancy, they also lose more life years. Those transplanted for cancer, hepatitis C virus infection, and alcoholic liver disease had the greatest loss of life years.
13C-urea breath test for diagnosis of experimental Helicobacter pylori infection in barrier born pigs.
Authors: K Meyer-Rosberg, S Gustavsson
Journal: Gut (1993)

Previous studies with Helicobacter pylori infected barrier born pigs indicate that the infection has a patchy distribution, resulting in false negative culture results on endoscopic biopsy specimens. This study aimed to adapt the 13C-urea breath test as used in humans to diagnose H pylori infection in barrier born pigs. The breath test was also performed after bismuth as a single treatment and after triple therapy (bismuth, ampicillin, metronidazole). In control pigs the median excess of 13CO2 in expired air was 2.2 (range 0-12 n = 22) ppm. The infected pigs (n = 4) showed consistently high values (median 23 range 14-43) when examined on four occasions (n = 16) four to 10 weeks after inoculation. Biopsy specimens for culture had lower sensitivity than the breath test. No reduction in excess 13CO2 was seen after three days9 single bismuth treatment, but after two weeks9 triple therapy the breath test results had returned to normal. This suppression was temporary only, however, as the breath test was positive again four weeks after stopping treatment. In conclusion, the 13C-urea breath test is a simple and reliable test for determining H pylori infection and monitoring treatment effects in barrier born pigs. Because the test can be performed in awake pigs anaesthesia and gastroscopy are unnecessary.
Tumour necrosis factor and nuclear factor B inhibit transcription of human TFF3 encoding a gastrointestinal healing peptide
Authors: M B Loncar
Journal: Gut (2003)

and aims: Tumour necrosis factor alpha (TNF-alpha) induction of nuclear factor kappaB (NFkappaB) activation plays a major role in the pathogenesis of inflammatory bowel disease (IBD). Trefoil factor family peptides TFF1, TFF2, and TFF3 exert protective, curative, and tumour suppressive functions in the gastrointestinal tract. In this study, we investigated effects of the TNF-alpha/NFkappaB regulatory pathway by TNF-alpha on expression of TFFs.After TNF-alpha stimulation, expression of TFF genes was analysed by quantitative real time polymerase chain reaction and by reporter gene assays in the gastrointestinal tumour cell lines HT-29 and KATO III. Additionally, NFkappaB subunits and a constitutive repressive form of inhibitory factor kappaB (IkappaB) were transiently coexpressed. In vivo, morphological changes and expression of TFF3, mucins, and NFkappaB were monitored by immunohistochemistry in a rat model of 2,4,6-trinitrobenzene sulphonic acid induced colitis.TNF-alpha stimulation evoked up to 10-fold reduction of TFF3 expression in the colon tumour cell line HT-29. Downregulation of reporter gene transcription of TFF3 was observed with both TNF-alpha and NFkappaB, and was reversible by IkappaB. In vivo, the increase in epithelial expression of NFkappaB coincided with reduced TFF3 expression during the acute phase of experimental colitis.Downregulation of intestinal trefoil factor TFF3 is caused by repression of transcription through TNF-alpha and NFkappaB activation in vitro. In IBD, perpetual activation of NFkappaB activity may contribute to ulceration and decreased wound healing through reduced TFF3.
Mitochondrial gene mutation and insulin-deficient type of diabetes mellitus
Authors: Hiroko Kadowaki, Kazuyuki Tobe, Yasumichi Mori, Hiroshi Sakura, Ryoichi Sakuta, Ikuya Nonaka, Ryoko Hagura, Yoshi Yazaki, Yasuo Akanuma, Takashi Kadowaki
Journal: The Lancet (1993)
Randomised trial of a brief physiotherapy intervention compared with usual physiotherapy for neck pain patients: outcomes and patients' preference
Authors: Jennifer A Klaber Moffett, David A Jackson, Stewart Richmond, Seokyung Hahn, Simon Coulton, Amanda Farrin, Andrea Manca, David J Torgerson
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objectives</b> Firstly, to compare the effectiveness of a brief physiotherapy intervention with “usual” physiotherapy for patients with neck pain. Secondly, to evaluate the effect of patients9 preferences on outcome. <b>Design</b> Non-inferiority randomised controlled trial eliciting preferences independently of randomisation. <b>Setting</b> Physiotherapy departments in a community setting in Yorkshire and north Lincolnshire. <b>Participants</b> 268 patients (mean age 48 years) with subacute and chronic neck pain, who were referred by their general practitioner and randomly assigned to a brief physiotherapy intervention (one to three sessions) using cognitive behaviour principles to encourage self management and return to normal function or usual physiotherapy, at the discretion of the physiotherapist concerned. <b>Main outcome measures</b> The Northwick Park neck pain questionnaire (NPQ), a specific measure of functional disability resulting from neck pain. Also, the short form 36 (SF-36) questionnaire, a generic, health related, quality of life measure; and the Tampa scale for kinesophobia, a measure of fear and avoidance of movement. <b>Results</b> At 12 months, patients allocated to usual physiotherapy had a small but significant improvement in NPQ scores compared with patients in the brief intervention group (mean difference 1.99, 95% confidence interval 0.45 to 3.52; P = 0.01). Although the result shows a significant inferiority of the intervention, the confidence interval shows that the effect could be in the non-inferiority range for the brief intervention (below 1.2 points of NPQ score). Patients who preferred the brief intervention and received this treatment had similar outcomes to patients receiving usual physiotherapy. <b>Conclusions</b> Usual physiotherapy may be only marginally better than a brief physiotherapy intervention for neck pain. Patients with a preference for the brief intervention may do at least as well with this approach. Additional training for the physiotherapists in cognitive behaviour techniques might improve this approach further.
Localization of lanthanum in bone of chronic renal failure rats after oral dosing with lanthanum carbonate
Authors: Geert J. Behets, Steven C. Verberckmoes, Line Oste, An R. Bervoets, Murielle Salomé, Alan G. Cox, John Denton, Marc E. De Broe, Patrick C. D'Haese
Journal: Kidney International (2005)