tbuckley/cabot-search huggingface dataset:
Lactate and gas exchange responses to incremental and steady state running.
Authors: M Haverty, W L Kenney, J L Hodgson
Journal: British Journal of Sports Medicine (1988)

This study compared the oxygen uptake (VO2) and running velocity at which the lactate threshold (LT), the ventilatory threshold (VT), and the maximal lactate steady state (MSSLA), and the maximal VO2 steady state (MSSVO2) occurred in 11 trained male runners (mean age = 22.4 years, range 18-28 years). Each underwent an incremental treadmill test to exhaustion. The LT was defined by a systematic, continuous increase in arterialised venous blood lactate; the VT was determined by an abrupt rise in VE.VO2(-1) without an increase in VE.VCO2(-1). Each subject also completed a series of steady state treadmill runs of 20 minutes duration. The MSSLA was determined as the highest velocity and VO2 at which lactate concentration increased by less than 0.2 mmol.l-1 from minute 10 to minute 20. The MSSVO2 was determined as the highest velocity or VO2 at which a steady state in VO2 was not delayed for more than 3 minutes (with a steady state defined as VO2 within 0.2 l.min-1 of the average VO2 over the last 10 minutes of each test). Each subject also completed a 5 km time trial run to assess performance. No significant differences were found among the four variables expressed either as VO2 or velocity. Significant correlations were found between MSSLA and MSSVO2 (r = 0.74) expressed as VO2, and between MSSLA and MSSVO2 (r = 0.90), MSSVO2 and VT (r = 0.70) and MSSLA and VT (r = 0.67) expressed as velocity. A stepwise regression analysis found MSSLA (expressed as velocity) to be the best predictor of 5 km performance (r = 0.87). It was concluded that (a) MSSLA and MSSVO2 are closely related, and (b) MSSLA is a good predictor of performance and may be an important, objective measure of cardiorespiratory endurance capacity.
Effect of Cellular Senescence on the Growth of HER2-Positive Breast Cancers
Authors: M. F. Zacarias-Fluck, B. Morancho, R. Vicario, A. Luque Garcia, M. Escorihuela, J. Villanueva, I. T. Rubio, J. Arribas
Journal: JNCI Journal of the National Cancer Institute (2015)

Oncogene-induced senescence (OIS) is a tumor suppressor mechanism. However, senescent cells remain viable and display a distinct secretome (also known as senescence-associated secretory phenotype [SASP] or senescence messaging secretome, [SMS]) that, paradoxically, includes protumorigenic factors. OIS can be triggered by ectopic overexpression of HER2, a receptor tyrosine kinase and the driving oncogene in a subtype of human breast cancer. However, cellular senescence has not been characterized in HER2-positive tumors. Using an approach based on their inability to proliferate, we isolated naturally occurring senescent cells from a variety of tumor models including HER2-positive cells, transgenic mice (n = 3), and patient-derived xenografts (PDXs) (n = 6 mice per group from one PDX derived from one patient). Using different biochemical and cell biological techniques, we characterized the secretome of these senescent cells. All statistical tests were two-sided. We found that senescent cells arise constantly in different models of advanced breast cancers overexpressing HER2 and constitute approximately 5% of tumor cells. In these models, IL-6 and other cytokines were expressed mainly, if not exclusively, by the naturally occurring senescent cells (95.1% and 45.0% of HCC1954 cells and cells from a HER2-positive PDX expressing a senescent marker expressed IL-6, respectively). Furthermore, inhibition of IL-6 impaired the growth of the HER2-positive PDX (mean tumor volume at day 101, control vs anti–huIL-6 treated, 332.2mm 3 [95% confidence interval {CI} = 216.6 to 449.8] vs 114.4mm 3 [95% CI = 12.79 to 216.0], P = .005). Senescent cells can contribute to the growth of tumors by providing cytokines not expressed by proliferating cells, but required by these to thrive.
Prejudice and personality: A role for positive-approach processes?
Authors: Charles Seger, Philip J. Corr
Journal: Behavioral and Brain Sciences (2012)

Abstract Individuals differ in their support for social change. We argue that examinations of inequality and change would benefit from consideration of underlying personality processes. New data suggest that Right-Wing Authoritarianism and Social Dominance Orientation, indicators of support for inequality, may be motivated by biologically driven personality processes, particularly those related to positive-approach motivation.
Mechanisms underlying ventricular tachycardia and its transition to ventricular fibrillation in the structurally normal heart
Authors: F Samie
Journal: Cardiovascular Research (2001)

Reentrant ventricular tachycardia (VT) is the most common sustained arrhythmia leading to ventricular fibrillation (VF). However, despite more than a century of research, the mechanism(s) of the conversion from reentrant VT to VF have not been elucidated. Based on their different electrocardiographic appearance, reentrant VT and VF have traditionally been thought of as resulting from two widely different mechanisms. Whereas VT is seen as a rapid but well organized process whereby the excitation wave rotates about a single well-defined circuit, fibrillation has been described as turbulent cardiac electrical activity, resulting from the random and aperiodic propagation of multiple independent wavelets throughout the cardiac muscle. Recently, the application of concepts derived from the theory of non-linear dynamics to the problem of wave propagation in the heart and the advent of modern high-resolution mapping techniques, have led some investigators to view VT and VF in terms of a single mechanism, whereby the self-organization of electrical waves forms 'rotors' that give rise to rapidly rotating spiral waves and results in either VT or VF, depending on the frequency of rotation and on the interaction of wave fronts with the cardiac muscle. As such, monomorphic VT is thought to result from a stationary rotor, whose frequency of rotation is within a range that allows 1:1 excitation of both ventricles. On the other hand, VF is thought to result from either a single rapidly drifting rotor, or a stationary rotor whose frequency of excitation is exceedingly high, thus resulting in multiple areas of intermittent block and giving rise to complex patterns of propagation with both deterministic and stochastic components. This article reviews the prevailing theories for the maintenance of VF, and discusses recently proposed mechanisms underlying transitions between VT and VF.
External validation of a prognostic scoring system for percutaneous endoscopic gastrostomy (PEG)
Authors: M. Kurien, H. E. Robson, J. S. Leeds, J. Grant, M. E. McAlindon, K. L. Dear, B. S. Hoeroldt, K. Kapur, G. James, D. S. Sanders
Journal: Gut (2011)

<h3>Introduction</h3> There is a significant mortality associated with PEG. The Sheffield Gastrostomy Score (SGS) was devised to try and improve outcomes following this procedure by predicting 30-day mortality. After prospectively collecting demographic, biochemical and outcome data from a cohort of patients having a new PEG inserted (Hospital A, n = 403), multivariate analysis identified that age and albumin were determinants of 30-day mortality (p &lt; 0.001). Age and albumin were attributed scores in a scoring system, the SGS, with age scoring 0 or 1 (&lt;65/≤65 years) and albumin scoring 0, 1 or 2 (&gt;35, 25–34 and &lt;25 g/L). Composite scores in the SGS of 0 to 3 corresponded to 30-day mortalities of 0%, 7%, 21.3% and 37.3%, respectively. The SGS was then validated on a separate cohort of patients from a second hospital in Sheffield, from within the same trust (Internal validation: Hospital B, n = 153) with comparable 30-day mortality figures. Thus our aim was to externally validate the SGS (outside of Sheffield) and determine its potential application to a wider population. <h3>Methods</h3> Four local district general hospitals were used to externally validate the SGS. Demographic, biochemical and outcome data was obtained from all patients undergoing PEG insertion between June 2006 and June 2009. χ<sup>2</sup> analysis was used to compare actual 30-day mortality rates in the external cohort to the rate predicted by the SGS. <h3>Results</h3> A total of 679 new PEGs were inserted during this period in these four hospitals. Complete records were obtained from 88% (597/679) and analysed (median age 71, 322 male). The 30-day mortality for this external validation cohort was 13.6%. The main indications for PEG insertion were stroke (33.7%), oropharyngeal malignancy (32.3%) and neurodegenerative diseases (17.4%). Univariate analysis predictors of 30-day mortality in this external cohort were: increasing age, low serum albumin and stroke. There were no significant differences between the observed and the predicted mortality (p ≤ 0.05) in the external validation cohort using the SGS. <h3>Conclusion</h3> Our results suggest that the SGS can accurately stratify patients into different risk categories, with higher scores correlating with significantly lower survival. We feel that the SGS could have an important role in those patients where the benefits and risks of gastrostomy are unclear.
Extramedullary Hematopoiesis Generates Ly-6C <sup>high</sup> Monocytes That Infiltrate Atherosclerotic Lesions
Authors: Clinton S. Robbins, Aleksey Chudnovskiy, Philipp J. Rauch, Jose-Luiz Figueiredo, Yoshiko Iwamoto, Rostic Gorbatov, Martin Etzrodt, Georg F. Weber, Takuya Ueno, Nico van Rooijen, Mary Jo Mulligan-Kehoe, Peter Libby, Matthias Nahrendorf, Mikael J. Pittet, Ralph Weissleder, Filip K. Swirski
Journal: Circulation (2011)

Background— Atherosclerotic lesions are believed to grow via the recruitment of bone marrow–derived monocytes. Among the known murine monocyte subsets, Ly-6C high monocytes are inflammatory, accumulate in lesions preferentially, and differentiate. Here, we hypothesized that the bone marrow outsources the production of Ly-6C high monocytes during atherosclerosis. Methods and Results— Using murine models of atherosclerosis and fate-mapping approaches, we show that hematopoietic stem and progenitor cells progressively relocate from the bone marrow to the splenic red pulp, where they encounter granulocyte macrophage colony-stimulating factor and interleukin-3, clonally expand, and differentiate to Ly-6C high monocytes. Monocytes born in such extramedullary niches intravasate, circulate, and accumulate abundantly in atheromata. On lesional infiltration, Ly-6C high monocytes secrete inflammatory cytokines, reactive oxygen species, and proteases. Eventually, they ingest lipids and become foam cells. Conclusions— Our findings indicate that extramedullary sites supplement the hematopoietic function of the bone marrow by producing circulating inflammatory cells that infiltrate atherosclerotic lesions.
A Double-blind, Placebo-controlled, Randomized, Crossover Trial Of a Mint Tea High In Rosmarinic Acid In Adults With Nasal Polyposis
Authors: L.T. Goronfolah, P. Ferrie, M. Schmuck, S. Waserman, J. Denburg, L. Kott, P. Keith, L. Crawford, R. Fletcher
Journal: Journal of Allergy and Clinical Immunology (2009)
Clinical evaluation (phase I) of a combination of two human monoclonal antibodies to HBV: Safety and antiviral properties
Authors: Eithan Galun, Rachel Eren, Rifaat Safadi, Yaffa Ashour, Norah Terrault, Emmet B. Keeffe, Edith Matot, Sara Mizrachi, Dov Terkieltaub, Merav Zohar, Ido Lubin, Judith Gopher, Daniel Shouval, Shlomo Dagan
Journal: Hepatology (2002)

Treatment of chronic hepatitis B virus (HBV) infection with interferon alfa and lamivudine is characterized by lack of viral clearance, loss of response, or emergence of drug-resistant mutants. Thus, new and multiple drug approaches are needed. We have developed two fully human monoclonal antibodies, directed against different epitopes of hepatitis B surface antigen (HBsAg) that bind to all major HBV subtypes. A phase I clinical study was conducted to evaluate the safety, tolerability, and efficacy of a mixture of these two monoclonal antibodies, HBV-AB(XTL). A total of 27 chronic HBV patients were enrolled. In part A of the study 15 patients in 5 cohorts received a single intravenous infusion of antibodies with doses ranging from 0.26 mg (260 IU) to 40 mg (40,000 IU). All patients completed 16 weeks of follow-up. In the second part of the study (part B), 12 patients in 4 cohorts received 4 weekly infusions of 10, 20, 40, or 80 mg each of HBV-AB(XTL) and were followed for 4 additional weeks. Administration of antibodies was well tolerated. Patients administered doses at an Ab:Ag molar ratio of 1:2 to 1:20 showed a rapid and significant decrease in HBsAg to undetectable levels, with a corresponding reduction of HBV-DNA levels. In part B, HBV-AB(XTL) induced a significant reduction in both HBsAg and HBV-DNA levels repeatedly after administration. In conclusion, these data suggest that HBV-AB(XTL) binds HBV particles and reduces serum viral titers and HBsAg levels. HBV-AB(XTL) could be combined with other monotherapies that are currently used to treat HBV carriers.
Chlorination by-products in drinking water and menstrual cycle function.
Authors: Gayle C Windham, Kirsten Waller, Meredith Anderson, Laura Fenster, Pauline Mendola, Shanna Swan
Journal: Environmental Health Perspectives (2003)

We analyzed data from a prospective study of menstrual cycle function and early pregnancy loss to explore further the effects of trihalomethanes (THM) on reproductive end points. Premenopausal women ((italic)n(/italic) = 403) collected urine samples daily during an average of 5.6 cycles for measurement of steroid metabolites that were used to define menstrual parameters such as cycle and phase length. Women were asked about consumption of various types of water as well as other habits and demographics. A THM level was estimated for each cycle based on residence and quarterly measurements made by water utilities during a 90-day period beginning 60 days before the cycle start date. We found a monotonic decrease in mean cycle length with increasing total THM (TTHM) level; at &gt; 60 microg/L, the adjusted decrement was 1.1 days [95% confidence interval (CI), -1.8 to -0.40], compared with less than or equal to 40 microg/L. This finding was also reflected as a reduced follicular phase length (difference -0.94 day; 95% CI, -1.6 to -0.24). A decrement in cycle and follicular phase length of 0.18 days (95% CI, -0.29 to -0.07) per 10 microg/L unit increase in TTHM concentration was found. There was little association with luteal phase length, menses length, or cycle variability. Examining the individual THMs by quartile, we found the greatest association with chlorodibromomethane or the sum of the brominated compounds. Incorporating tap water consumption showed a similar pattern of reduced cycle length with increasing TTHM exposure. These findings suggest that THM exposure may affect ovarian function and should be confirmed in other studies.
A role of SMAD4 in iron metabolism through the positive regulation of hepcidin expression
Authors: Rui-Hong Wang, Cuiling Li, Xiaoling Xu, Yin Zheng, Cuiying Xiao, Patricia Zerfas, Sharon Cooperman, Michael Eckhaus, Tracey Rouault, Lopa Mishra, Chu-Xia Deng
Journal: Cell Metabolism (2005)
Fibrous and obliterative cholangitis in liver allografts: Evidence of recurrent primary sclerosing cholangitis?
Authors: Rebecca F. Harrison, Mervyn H. Davies, James M. Neuberger, Stefan G. Hubscher
Journal: Hepatology (1994)

Fibroobliterative lesions and fibrous cholangitis are characteristic histological lesions of primary sclerosing cholangitis. To determine whether such lesions can be found in the liver allograft, and whether they represent recurrent disease, we reviewed all consecutive histological material taken at greater than 6 mo after transplantation in a 3-yr period from a series of 207 liver transplantations (22 with primary sclerosing cholangitis, 185 controls without primary sclerosing cholangitis). Because patients with primary sclerosing cholangitis have a biliary system reconstructed by means of a Roux loop, we compared the findings with those from a further control group of patients who had received a Roux loop for reasons other than primary sclerosing cholangitis. Of 22 patients receiving liver transplants for primary sclerosing cholangitis, 7 (32%) patients had biopsy specimens showing features of biliary obstruction, 6 (27%) showed fibrous cholangitis, and 3 (14%) showed classic fibroobliterative lesions. These findings compared with 3 (14%), 1 (5%) and 0 of 22 Roux controls, and 19 (10%), 4 (2%) and 0 of 185 controls without primary sclerosing cholangitis, respectively. The three patients with fibroobliterative lesions either had clinical episodes of cholangitis or had microorganisms in the large bile ducts. However, both biliary obstructive features and fibrous cholangitis were more common in primary sclerosing cholangitis, and fibroobliterative lesions were found only in patients who received transplants for primary sclerosing cholangitis, despite the presence of cholangitis and Roux loops in control patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Pneumonitis and pulmonary fibrosis associated with amiodarone treatment: a possible complication of a new antiarrhythmic drug.
Authors: S M Sobol, L Rakita
Journal: Circulation (1982)

Six patients are presented who developed pulmonary infiltrates of undetermined origin while being treated for severe ventricular arrhythmias with amiodarone hydrochloride. Biopsy material was available in four patients and revealed interstitial or alveolar fibrosis and pneumonitis. Four patients recovered and two died of severe cardiopulmonary decompensation; all of the patients who recovered received corticosteroid therapy. Pulmonary fibrosis is a previously unreported complication of amiodarone therapy.
&lt;italic&gt;N&lt;/italic&gt;-Nitrosomethylurea as Mammary Gland Carcinogen in Rats
Authors: P M Gullino, H M Pettigrew, F H Grantham
Journal: JNCI Journal of the National Cancer Institute (1975)

N-nitrosomethylurea (NMU) given intravenously to rats at age 50 days induced mammary carcinomas in 89% of BUF/N, 73% of Sprague-Dawley, and 89% of F344 females. Latent periods were, respectively, 77, 86, and 94 days. Mortality was negligible. Biologic properties of NMU-induced tumors were tested in the BUF/N inbred strain. Before treatment, it reduced the number of tumors per rat but not the incidence; and after the tumor was established, castration arrested tumor growth or caused a temporary regression of the tumor. Metastases to bone marrow and spleen were constant, but they were rare to the liver and lungs. After the primary tumor was removed, metastases continued to grow but at a slower rate than the growth of the primary tumor. Almost all tumors were transplantable intraperitoneally and/or subcutaneously in the inguinal area of intact as well as ovariectomized and adrenalectomized rats. Transplanted tumors were able to metastasize as were primary tumors. Doubling times of NMU-induced primary and transplanted carcinomas were similar to 7 days. Cachexia ensued at the 5th week from the onset of the first tumor. When the tumor was larger than 15 g, hypercalcemia was usually observed. The treatment described appears to be the simplest method for inducing in rats a most nearly complete model for human mammary carcinomas.
Molecular analysis of the bare lymphocyte syndrome.
Authors: K E Sullivan, J D Stobo, B M Peterlin
Journal: Journal of Clinical Investigation (1985)

The bare lymphocyte syndrome is a disorder in which class I histocompatibility antigens fail to be expressed normally on the surface of lymphocytes. Utilizing complementary DNA probes for both beta 2-microglobulin and class I genes, the molecular basis for this syndrome was investigated in a family with two siblings exhibiting the bare lymphocyte syndrome. Southern blot analysis demonstrated no gross internal defect in either class I or beta 2-microglobulin genes. Northern blot analysis of class I and beta 2-microglobulin messenger RNAs also revealed no qualitative difference between affected and unaffected family members. In contrast, quantitation of both class I and beta 2-microglobulin transcripts demonstrated each to be decreased in patients when compared to controls. Moreover, the decrease in both transcripts was coordinate. These results suggest that the bare lymphocyte syndrome may represent a pretranslational regulatory defect of both class I and beta 2-microglobulin gene expression.
Influence of intestinal bacteria on induction of regulatory T cells: lessons from a transfer model of colitis
Authors: U G Strauch
Journal: Gut (2005)

The resident flora plays a critical role in initiation and perpetuation of intestinal inflammation, as demonstrated in experimental models of colitis where animals fail to develop disease under germ free conditions. However, the importance of exposure to commensal bacteria before the onset of colitis is unclear. Our aim was to investigate the influence of previous exposure of donor animals to bacterial antigens on colitis development using a transfer model.Clinical course and histology were evaluated after transfer of CD4(+)CD62L(+) lymphocytes from germ free and conventionally housed donor mice into SCID recipients. Cotransfer of CD4(+)CD62L(+) cells with CD4(+)CD62L(- )lymphocytes from both groups of mice was initiated. Lymphocytes were analysed by FACS, polarisation potential of cells determined, and cytokines measured within the supernatant by enzyme linked immunosorbent assay.Animals that received cells from germ free donors developed an earlier onset of colitis compared with mice reconstituted with lymphocytes from conventionally housed animals. Additionally, CD4(+)CD62L(- )cells from germ free mice were not able to abrogate colitis induced by cotransfer with CD4(+)CD62L(+) lymphocytes whereas CD4(+)CD62L(- )T cells from normal mice ameliorated disease. The higher percentage of CD4(+)GITR(+) expressing lymphocytes and the production of interleukin 10 after priming by dendritic cells suggests the presence of T(reg) cells within the CD4(+)CD62L(+) lymphocyte subset derived from conventional housed mice and assumes a lack of T(reg) cells within germ free mice.The results indicate that bacterial antigens are crucial for the generation and/or expansion of T(reg) cells in a healthy individual. Therefore, bacterial colonisation is of great importance in maintaining the immunological balance.
Organ-Specific Increase in Mutation Accumulation and Apoptosis Rate in CuZn-Superoxide Dismutase–Deficient Mice
Authors: Rita A. Busuttil, Ana Maria Garcia, Carlos Cabrera, Armando Rodriguez, Yousin Suh, Woo Ho Kim, Ting-Ting Huang, Jan Vijg
Journal: Cancer Research (2005)

Abstract Reactive oxygen species have been implicated as a cause of cancer and aging in mammals. Mice deficient for the antioxidant enzyme CuZn-superoxide dismutase (Sod1) have a decreased life span and an elevated incidence of liver cancer. To test the hypothesis that the cancer-prone phenotype in such mice is due to accelerated spontaneous mutation accumulation, we crossed these mutants with mice harboring a neutral lacZ mutation reporter gene. At 2 months of age, the lacZ mutation frequency in the liver of the hybrid animals was already twice as high as in littermate controls of the same age. This difference in mutation frequency increased to &amp;gt;3-fold at 6 months of age, after which it did not increase any further. Characterization of the mutation spectra in liver of the Sod1-null mice indicated mainly GC-to-TA transversions and GC-to-AT transitions, signature mutations of oxidative stress. The accelerated mutation accumulation in liver was accompanied by an increased frequency of apoptotic cells, as indicated by an increase in both terminal deoxyribonucleotidyl transferase–mediated dUTP nick end labeling– and caspase 3–stained cells at 6 and 12 months of age. In kidney, an elevated mutation frequency above controls of ∼2.5-fold was found not earlier than at 6 months. No increased mutation accumulation was observed in brain or spleen. These results support the hypothesis, that oxidative stress is an important causal factor of cancer in mammals. (Cancer Res 2005; 65(24): 11271-5)