tbuckley/cabot-search huggingface dataset:
Environmental Risk Conditions and Pathways to Cardiometabolic Diseases in Indigenous Populations
Authors: Mark Daniel, Peter Lekkas, Margaret Cargo, Ivana Stankov, Alex Brown
Journal: Annual Review of Public Health (2011)

This review examines environments in relation to cardiometabolic diseases in Indigenous populations in developed countries. Environmental factors are framed in terms of context (features of places) and composition (features of populations). Indigenous peoples are seen to have endured sociopolitical marginalization and material disadvantage spanning generations. Past adverse collective experiences, modified by culture, are reflected by current heterogeneity in environmental context and composition. As risk conditions, unfavorable contextual and compositional exposures influence the expression of cardiometabolic risk for individuals. Minimal research has evaluated heterogeneity in risk conditions against heterogeneity in cardiometabolic diseases between or within Indigenous populations. Thus far, the features of populations, not of places themselves, have been implicated in relation to cardiometabolic diseases. Behavioral, psychosocial, and stress-axis pathways may explain the relationships between risk conditions and cardiometabolic diseases. Implications of environmental factors and their pathways as well as important research needs are discussed in relation to ecological prevention to reduce cardiometabolic diseases.
Estrogen Receptor-α Phosphorylation at Serine-118 and Tamoxifen Response in Breast Cancer
Authors: Marleen Kok, Caroline Holm-Wigerup, Michael Hauptmann, Rob Michalides, Olle Stål, Sabine Linn, Göran Landberg
Journal: JNCI Journal of the National Cancer Institute (2009)

Although estrogen receptor-alpha (ER) [corrected] is a marker used to identify breast cancer patients most likely to benefit from endocrine therapy, approximately 50% of ER-positive [corrected] breast carcinomas are resistant to tamoxifen. Preclinical studies have shown that phosphorylation of ER [corrected] at serine-118 (ER alpha S118-P) is required for tamoxifen-mediated inhibition of ER-induced [corrected] gene expression. We evaluated the association between recurrence-free survival after tamoxifen treatment and ER alpha S118-P expression by use of Cox proportional hazards regression. Data were from 239 premenopausal patients with breast cancer who participated in a randomized trial of 2 years of adjuvant tamoxifen treatment vs no systemic treatment. ER alpha S118-P expression was assessed by immunohistochemistry and categorized by use of the Allred score (low expression = score of 0-6; high expression = score of 7-8). All statistical tests were two-sided. Compared with systemically untreated patients, we found evidence of a benefit from adjuvant tamoxifen among patients whose tumors had high ER alpha S118-P expression (23.7 recurrences per 1000 person-years versus 72.2 recurrences per 1000 person-years, hazard ratio [HR] of recurrence = 0.36, 95% confidence interval [CI] = 0.20 to 0.65) but not among patients whose tumors had low expression (51.0 recurrences per 1000 person-years versus 57.0 recurrences per 1000 person-years, HR of recurrence = 0.87, 95% CI = 0.51 to 1.48), a statistically significant difference (P for interaction = .037). ER alpha 118-P was not associated with recurrence-free survival among untreated patients. Thus, ER alpha S118-P expression appears to be associated with response to tamoxifen. [corrected]
Influence of Shift Work and Host Factors on Endotoxin-related Acute Peak Flow Changes
Authors: JAN-PAUL ZOCK, DICK HEEDERIK, BERT BRUNEKREEF
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

There is limited knowledge about which internal and external factors influence respiratory effects of occupational endotoxin exposure. Relationships between endotoxin exposure, work-related respiratory symptoms, and acute peak flow changes were studied in 97 shift workers in the potato processing industry. For each worker, across-shift peak flow changes were determined for morning, afternoon, and night shifts. A higher endotoxin exposure was associated with an increased prevalence of work-related symptoms, a smaller peak expiratory flow (PEF) increase across the morning shift, and a larger PEF decrease across afternoon and night shifts. The largest effects occurred during the afternoon shift. No consistent differences between smokers and nonsmokers, and between atopics and nonatopics were observed. We conclude that endotoxin exposure in the potato processing industry is related to across-shift peak flow changes and the occurrence of work-related respiratory symptoms. The host factors smoking and atopy are not important confounding or effect-modifying factors in these relationships. In respiratory health studies among shift workers, it is important to investigate all work shifts before drawing definitive conclusions about exposure–response relationships.
Central sleep apnoea in Arnold-Chiari malformation: evidence of pathophysiological heterogeneity
Authors: C Rabec, G Laurent, N Baudouin, M Merati, F Massin, P Foucher, L Brondel, O Reybet-Degat
Journal: European Respiratory Journal (1998)

We report on the case of two young patients with type I Arnold-Chiari malformation (ACM), as revealed by a central sleep apnoea (CSA) syndrome without any other neurological defect. Case 1 was a 14-yr-old male patient, who developed severe alveolar hypoventilation and needed long-term mechanical ventilation via a tracheostomy. Case 2 was a 39-yr-old male patient, who developed features suggestive of sleep apnoea and responded to nasal continuous positive airway pressure ventilation despite the central type of apnoeas. These two cases illustrate the different pathophysiological mechanisms involved in CSA, namely a blunted chemical drive (in hypercapnic patients) and an increased chemical drive, which destabilizes the breathing pattern during sleep (in normo/hypocapnic patients). Central sleep apnoea can be the initial manifestation of Arnold-Chiari malformation and can lead to a life-threatening condition.
Gastrokine 1 induces senescence through p16/Rb pathway activation in gastric cancer cells
Authors: Rui Xing, Wenmei Li, Jiantao Cui, Jun Zhang, Bin Kang, Yuan Wang, Zhaohui Wang, Siqi Liu, Youyong Lu
Journal: Gut (2011)

<h3>Background and aims</h3> Gastrokine 1 (GKN1) is a stomach-specific protein that is normally expressed in gastric mucosa but not in primary tumours and cell lines. Based on this evidence, it was presumed that GKN1 might play a role in gastric cancer development; however, its function and molecular mechanism are not clear. A systematic study was initiated that combined multiple approaches to define the molecular mechanism of GKN1 in gastric cancer cells. <h3>Method</h3> Proteomics, western blotting and immunohistochemistry were used to measure the expression level of GKN1. Western blotting combined with immunofluorescence was used to monitor the secretory process of this protein. Subsequently, the function and molecular mechanism of GKN1 was explored in vitro and in vivo. <h3>Results</h3> It was shown that GKN1 is an autocrine/paracrine protein and inhibits cell growth due to senescence, which resulted from activation of p16/Rb and p21<sup>waf</sup> pathways. Furthermore, sustained activation of Ras/Raf/MEK/ERK signalling was characterised in gastric cancer cells and a xenograft nude mouse model following GKN1 treatment. <h3>Conclusion</h3> These results provide comprehensive molecular evidence of GKN1 in inducing senescence of gastric cancer cells, and indicate that GKN1 might be a potential novel target for gastric cancer therapeutics.
Stent thrombosis and major clinical events at 3 years after zotarolimus-eluting or sirolimus-eluting coronary stent implantation: a randomised, multicentre, open-label, controlled trial
Authors: Edoardo Camenzind, William Wijns, Laura Mauri, Volkhard Kurowski, Keyur Parikh, Runlin Gao, Christoph Bode, John P Greenwood, Eric Boersma, Pascal Vranckx, Eugene McFadden, Patrick W Serruys, William W O'Neil, Brenda Jorissen, Frank Van Leeuwen, Ph Gabriel Steg
Journal: The Lancet (2012)
Adipose tissue-derived stem cells as a regenerative therapy for a mouse steatohepatitis-induced cirrhosis model
Authors: Akihiro Seki, Yoshio Sakai, Takuya Komura, Alessandro Nasti, Keiko Yoshida, Mami Higashimoto, Masao Honda, Soichiro Usui, Masayuki Takamura, Toshinari Takamura, Takahiro Ochiya, Kengo Furuichi, Takashi Wada, Shuichi Kaneko
Journal: Hepatology (2013)

Cirrhosis is a chronic liver disease that impairs hepatic function and causes advanced fibrosis. Mesenchymal stem cells have gained recent popularity as a regenerative therapy since they possess immunomodulatory functions. We found that injected adipose tissue-derived stem cells (ADSCs) reside in the liver. Injection of ADSCs also restores albumin expression in hepatic parenchymal cells and ameliorates fibrosis in a nonalcoholic steatohepatitis model of cirrhosis in mice. Gene expression analysis of the liver identifies up- and down-regulation of genes, indicating regeneration/repair and anti-inflammatory processes following ADSC injection. ADSC treatment also decreases the number of intrahepatic infiltrating CD11b + and Gr-1 + cells and reduces the ratio of CD8 + /CD4 + cells in hepatic inflammatory cells. This is consistent with down-regulation of genes in hepatic inflammatory cells related to antigen presentation and helper T-cell activation. Conclusion : These results suggest that ADSC therapy is beneficial in cirrhosis, as it can repair and restore the function of the impaired liver. (Hepatology 2013;53:1133–1142)
Genetically characterized human liver cell lines (HEPG2) with distinct metabolic and toxicologic properties
Authors: Jos F. van Pelt, Hilde Bohets, Ronny Decorte, Peter Verboven, Veronique Van Genechten, Tania Roskams, Karel Lavrijsen, Paul S.H. Yap, Johan Fevery
Journal: Journal of Hepatology (2001)
The Index Case for the Fungal Meningitis Outbreak in the United States
Authors: April C. Pettit, Jonathan A. Kropski, Jessica L. Castilho, Jonathan E. Schmitz, Carol A. Rauch, Bret C. Mobley, Xuan J. Wang, Steven S. Spires, Meredith E. Pugh
Journal: New England Journal of Medicine (2012)

Persistent neutrophilic meningitis presents a diagnostic challenge, because the differential diagnosis is broad and includes atypical infectious causes. We describe a case of persistent neutrophilic meningitis due to Aspergillus fumigatus in an immunocompetent man who had no evidence of sinopulmonary or cutaneous disease. An epidural glucocorticoid injection was identified as a potential route of entry for this organism into the central nervous system, and the case was reported to the state health department.
Biochemical and biological characterization of lymphocyte regulatory molecules. I. Purification of a class of murine lymphokines.
Authors: J Watson, S Gillis, J Marbrook, D Mochizuki, K A Smith
Journal: The Journal of Experimental Medicine (1979)

Murine spleen cells activated by concanavalin A (Con A) in culture produce a class of lymphokine molecules which possess biological activity in a number of lymphocyte response assays. Lymphokines with a mol wt of 30,000, as estimated from gel filtration studies, can be resolved into two components which differ by charge, with isoelectric point (pI) values of 4.3 and 4.9, respectively. Both components stimulate (a) the growth of established T-cell lines in culture, (b) the proliferation of thymocytes in the presence of Con A under culture conditions where Con A alone is nonmitogenic, (c) the induction of antibody responses to heterologous erythrocyte antigens in athymic (nude) spleen cultures, (d) the generation of cytotoxic T lymphocytes (CTL) in thymocyte cultures, and (e) the generation of CTL in nude spleen cultures. In each of these culture systems we suggest that the assays are detecting a single class of lymphokine which acts directly on activated T cells. Nonactivated T cells must be stimulated by either antigen or mitogen before becoming responsive to lymphokine, but do not require antigen or mitogen for continued growth with lymphokine. The two molecular species, separable by isoelectric focusing are referred to as the T-cell growth factor (TCGF). A lymphokine, similar in size (30,000 daltons) to TCGF but heterogeneous in charge (pI 3.0--4.0), stimulates immune responses to erythrocyte antigens in T-cell-depleted spleen cultures but has no stimulatory activity in the other lymphocyte assay systems described. The data have been interpreted as showing the two molecular forms of murine TCGF (pI 4.3 and 4.9) are responsible for many of the lymphokine activities described elsewhere as thymocyte mitogenic factor, nonspecific T-cell-replacing factor and killer helper factor or costimulator. The other lymphokine, separable from TCGF by charge, appears to have true T-cell-replacing activity.
Cardiomyocyte-Specific Overexpression of Human Stem Cell Factor Improves Cardiac Function and Survival After Myocardial Infarction in Mice
Authors: Fu-Li Xiang, Xiangru Lu, Lamis Hammoud, Ping Zhu, Peter Chidiac, Jeffrey Robbins, Qingping Feng
Journal: Circulation (2009)

Soluble stem cell factor (SCF) has been shown to mobilize bone marrow stem cells and improve cardiac repair after myocardial infarction (MI). However, the effect of membrane-associated SCF on cardiac remodeling after MI is not known. The present study investigated the effects of cardiomyocyte-specific overexpression of the membrane-associated isoform of human SCF (hSCF) on cardiac function after MI.A novel mouse model with tetracycline-inducible and cardiac-specific overexpression of membrane-associated hSCF was generated. MI was induced by left coronary artery ligation. Thirty-day mortality after MI was decreased in hSCF/tetracycline transactivator (tTA) compared with wild-type mice. In vivo cardiac function was significantly improved in hSCF/tTA mice at 5 and 30 days after MI compared with wild-type mice. Endothelial progenitor cell recruitment and capillary density were increased and myocardial apoptosis was decreased in the peri-infarct area of hSCF/tTA mice. Myocyte size was decreased in hSCF/tTA mice 30 days after MI compared with WT mice. Furthermore, hSCF overexpression promoted de novo angiogenesis as assessed by matrigel implantation into the left ventricular myocardium.Cardiomyocyte-specific overexpression of hSCF improves myocardial function and survival after MI. These beneficial effects of hSCF may result from increases in endothelial progenitor cell recruitment and neovascularization and decreases in myocardial apoptosis and cardiac remodeling.
Gender-dependent hepatic alterations in H-ras12V transgenic mice
Authors: Ai-Guo Wang, Hyung-Bae Moon, Mi-Ran Lee, Chae Young Hwang, Ki-Sun Kwon, Seong-Lan Yu, Yong-Sung Kim, Mirang Kim, Jin-Man Kim, Sang-Keun Kim, Tae-Hoon Lee, Eun-Yi Moon, Dong-Seok Lee, Dae-Yeul Yu
Journal: Journal of Hepatology (2005)
Are there risk factors in alpine skiing? A controlled multicentre survey of 1278 skiers
Authors: R M Hasler, S Dubler, L M Benneker, S Berov, J Spycher, D Heim, H Zimmermann, A K Exadaktylos
Journal: British Journal of Sports Medicine (2009)

To analyse risk factors in alpine skiing.A controlled multicentre survey of injured and non-injured alpine skiers.One tertiary and two secondary trauma centres in Bern, Switzerland.All injured skiers admitted from November 2007 to April 2008 were analysed using a completed questionnaire incorporating 15 parameters. The same questionnaire was distributed to non-injured controls. Multiple logistic regression was performed. Patterns of combined risk factors were calculated by inference trees. A total of 782 patients and 496 controls were interviewed.Parameters that were significant for the patients were: high readiness for risk (p = 0.0365, OR 1.84, 95% CI 1.04 to 3.27); low readiness for speed (p = 0.0008, OR 0.29, 95% CI 0.14 to 0.60); no aggressive behaviour on slopes (p<0.0001, OR 0.19, 95% CI 0.09 to 0.37); new skiing equipment (p = 0.0228, OR 59, 95% CI 0.37 to 0.93); warm-up performed (p = 0.0015, OR 1.79, 95% CI 1.25 to 2.57); old snow compared with fresh snow (p = 0.0155, OR 0.31, 95% CI 0.12 to 0.80); old snow compared with artificial snow (p = 0.0037, OR 0.21, 95% CI 0.07 to 0.60); powder snow compared with slushy snow (p = 0.0035, OR 0.25, 95% CI 0.10 to 0.63); drug consumption (p = 0.0044, OR 5.92, 95% CI 1.74 to 20.11); and alcohol abstinence (p<0.0001, OR 0.14, 95% CI 0.05 to 0.34). Three groups at risk were detected: (1) warm-up 3-12 min, visual analogue scale (VAS)(speed) >4 and bad weather/visibility; (2) VAS(speed) 4-7, icy slopes and not wearing a helmet; (3) warm-up >12 min and new skiing equipment.Low speed, high readiness for risk, new skiing equipment, old and powder snow, and drug consumption are significant risk factors when skiing. Future work should aim to identify more precisely specific groups at risk and develop recommendations--for example, a snow weather index at valley stations.
What is the type-1/type-2 distinction?
Authors: Nick Chater
Journal: Behavioral and Brain Sciences (1997)

Clark &amp; Thornton's type-1/-2 distinction is not well-defined. The classes of type-1 and type-2 problems are too broad: many nocomputable functions are type-1 and type-2 learnable. They are also too narrow: trivial functions, such as identity, are neither type-1 nor type-2 learnable. Moreover, the scope of type-1 and type-2 problems appears to be equivalent. Overall, this distinction does not appear useful for machine learning or cognitive science.
The need for a focus on air pollution research in the elderly
Authors: T. Sandstrom, A.J. Frew, M. Svartengren, G. Viegi
Journal: European Respiratory Journal (2003)

During recent years an increasing focus has been directed towards the adverse health effects associated with ambient air pollution. Elderly people appear to be particularly susceptible to the adverse effects involving the respiratory and cardiovascular systems, resulting in symptoms, exacerbations of disease and even mortality. From an epidemiological point of view it is essential to obtain a more detailed description and identification of factors associated with these health effects. Novel study designs are needed with complementary exposure and biomedical characterisation. Long-term prospective studies are required. A better understanding of the pathophysiological mechanisms is considered important and requires an interaction between epidemiological and mechanistic studies in elderly individuals with or without complementary diseases that put in them especially at risk. Generally a synergy between complementary disciplines is warranted to move this important research area forward, also including in vitro models of cell responses in the elderly, animal models of diseases of the elderly, together with controlled air pollution exposure studies identifying health-related events and mechanisms. The generation of an understanding of air pollution effects in the elderly, at an elevated level, is a prerequisite to substantially reducing the adverse health effects of this population group. At local, national and European Union levels, some steps have been taken to support the research in this area. A major focus on the adverse air pollution effects in the elderly requires a long-term commitment that still remains to be established.
A Bioactively Modified Fatty Acid Improves Survival and Impairs Metastasis in Preclinical Models of Acute Leukemia
Authors: Per O. Iversen, Dag R. Sørensen, Karl J. Tronstad, Oddrun A. Gudbrandsen, Arild C. Rustan, Rolf K. Berge, Christian A. Drevon
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Polyunsaturated fatty acids (PUFA) and the sulfur-substituted fatty acid tetradecylthioacetic acid (TTA) inhibit proliferation and induce apoptosis in lymphoma and leukemic cell lines, but it is unknown if they can modify leukemogenesis in the intact organism. Experimental Design: We now examined the effects of PUFA and TTA in rats transplanted with either acute promyelocytic leukemia or acute T-cell leukemia. The rats were randomized to isoenergetic diets containing either lard (control), ω3 (n-3) PUFA, or TTA. Results: Whereas TTA prolonged survival (P &amp;lt; 0.05) in both types of rat leukemia, n-3 PUFA had no significant effect compared with controls. Only TTA inhibited (P &amp;lt; 0.05) leukemic infiltration in the bone marrow and spleen, probably due to apoptosis of the leukemic cells. Plasma metalloproteinase activity, a marker of metastatic activity, was significantly reduced in TTA-fed rats only. Conclusions: Dietary intake of TTA, but not of n-3 PUFA, in rats with acute leukemia, prolonged their survival. TTA intake was also associated with reduced leukemic cell burden as well as diminished extramedullar dissemination. TTA represents a modified fatty acid that exerts unique effects on malignant hematopoietic cells, and the present study indicates that TTA may have a therapeutic potential in patients with acute leukemias.
Relapsed or Refractory Anaplastic Large-Cell Lymphoma in Children and Adolescents After Berlin-Frankfurt-Muenster (BFM)–Type First-Line Therapy: A BFM-Group Study
Authors: Willi Woessmann, Martin Zimmermann, Meike Lenhard, Birgit Burkhardt, Claudia Rossig, Bernhard Kremens, Peter Lang, Andishe Attarbaschi, Georg Mann, Ilske Oschlies, Wolfram Klapper, Alfred Reiter
Journal: Journal of Clinical Oncology (2011)

To evaluate risk factors for outcome in children and adolescents with relapse of anaplastic large-cell lymphoma (ALCL) after comparable first-line therapy.We analyzed a population-based cohort of 74 children with relapsed ALCL after Berlin-Frankfurt-Muenster-type first-line therapy between April 1990 and December 2003. The recommended salvage strategy was reinduction chemotherapy followed by autologous hematopoietic stem-cell transplantation (SCT).With a median follow-up time of 8.4 years (range, 4.5 to 16.4 years), the 5-year overall survival (OS) rate after first relapse was 57% ± 6%. Survival correlated with time of relapse and clinically advanced dissemination. Five-year OS of 16 patients who experienced progression during first-line therapy was 25% ± 11% compared with 66% ± 6% for 58 patients with a later relapse (P = .002). Five-year OS of 11 patients with bone marrow or CNS involvement was 27% ± 13% compared with 62% ± 6% for 63 patients without involvement (P = .001). Five-year event-free survival (EFS) and OS of 39 children who received the recommended autologous SCT were 59% ± 8% and 77% ± 7%, respectively. EFS after autologous SCT was significantly associated with time to relapse (progression: n = 3; EFS, 0; later relapse: n = 36; EFS, 64% ± 8%; P = .014) and CD3 expression (CD3 negative: n = 25; EFS, 72% ± 9%; CD3 positive: n = 11; EFS, 18% ± 12%; P < .001), but not with site of relapse, conditioning regimen, or graft manipulation. No relapses occurred among 10 patients with relapsed CD3-positive ALCL treated with allogeneic SCT.Reinduction chemotherapy followed by autologous SCT proved feasible and efficacious for patients with a first relapse of CD3-negative ALCL after first-line therapy. Patients with progression during first-line therapy or relapsed CD3-positive ALCL may benefit from allogeneic SCT.
Genetic Study of Lymphoma Induction by Friend Murine Leukemia Virus in Crosses Involving AKR Mice2
Authors: Jonathan Silver
Journal: JNCI Journal of the National Cancer Institute (1986)

The AKR mouse strain is uniquely susceptible to thymic lymphoma. Friend murine leukemia virus (F-MuLV) induced thymic lymphoma in this strain after a median latency of 3–4 months, whereas in several other mouse strains F-MuLV caused erythroblastosis. In the investigation of genetic determinants of the AKR predisposition to thymic lymphoma, series of congenic mouse strains and progeny of crosses involving AKR mice were inoculated with F-MuLV; these mice were followed for the development of lymphoma. The results suggested that AKR genes on chromosomes 7 and 15, other than inherited ecotropic virus, are involved in the predisposition to rapid onset of thymic lymphoma after inoculation with F-MuLV.