tbuckley/cabot-search huggingface dataset:
Heat production during hypoxic contracture of rat myocardium.
Authors: C Holubarsch, N R Alpert, R Goulette, L A Mulieri
Journal: Circulation Research (1982)

Contracture due to hypoxia, to both oxygen and glucose deficiency, and to potassium chloride was induced in rat left ventricular papillary muscle preparations. Under contracture conditions, the sum of resting heat plus contracture heat was measured using Hill-type, planar vacuum-deposited thermopiles. On the basis of the measured total and initial heat output and the corresponding tension-time integral during single twitches under control conditions (Lmax, 21 degrees C, stimulus frequency 12/min), the expected heat output during contracture was calculated, assuming that the contracture tension is maintained by the same calcium-induced cross-bridge cycling as occurs in the single twitch response. With potassium chloride, the contracture tension was 1.33 +/- 0.27 g/mm2, a value which is similar to those found in hypoxic contracture and in contracture due to both oxygen and glucose deficiency. There was no significant difference between measured and calculated values for resting heat plus contracture heat (8.40 +/- 2.84 mW/g measured, 8.55 +/- 2.50 mW/g calculated); there was a linear correlation (r = 0.99) between predicted and measured values (P less than 0.05). The measured value for resting plus contracture heat in hypoxic contracture was 1.88 +/- 0.37 mW/g, whereas a value of 4.80 +/- 1.09 mW/g (P less than 0.005) was calculated on the basis of the twitch heat per tension-time integral and contracture tension (1.09 +/- 0.31 g/mm2). Contracture tension was 1.80 +/- 0.78 g/mm2 in contracture due to oxygen and glucose deficiency, whereas the value for resting plus contracture eat was 1.61 +/- 0.56 mW/g. The calculated resting plus contracture heat value for this preparation was significantly higher (7.45 +/- 3.75 mW/g; P less than 0.05). There was no significant regression between predicted and measured resting heat plus contracture heat in the hypoxic contracture preparations (slope not different from zero). In contracture due to oxygen and glucose deficiency, the linear regression had a slope of 6.06 (P less than 0.05). The results suggest that the potassium chloride contracture relies on cross-bridge cycling as in a twitch contraction, whereas hypoxic contracture and that due to oxygen and glucose deficiency may be explained by cross-bridge formations with no, or very low, heat production, i.e., contracture tensions due to hypoxia and to oxygen and glucose deficiency are maintained by rigor-like cross-bridge formation or by slowly cycling cross-bridges with a long time of cross-bridge attachment.
Neutrophils control the magnitude and spread of the immune response in a thromboxane A2-mediated process
Authors: Chiao-Wen Yang, Emil R. Unanue
Journal: The Journal of Experimental Medicine (2013)

Neutrophils are obligate cells entering lymph nodes shortly after immunization with protein antigens in adjuvants, starting during the first hour and continuing for several days in two distinct waves. Previously, we demonstrated the strong suppressive effects of neutrophils on CD4 T cell and B cell responses, using either neutrophil-depleting antibodies or genetically neutropenic mice. In this study, we find that neutrophils are the major cells controlling the spread of T cell responses to distal lymph nodes. Although in the presence of neutrophils, ∼75% of the response was restricted to the draining node, in their absence, most of the response was found in distal nodes. Prostanoids were responsible for the rapid entry of neutrophils into the draining nodes, as well as for the two distinct neutrophil effects: the modulation of the magnitude of the cellular response, and in its spread outside the draining nodes. Neutrophil-produced thromboxane A(2) was the key eicosanoid controlling both effects. Adoptive transfer of neutrophils into mice genetically deficient in neutrophils indicated their role in both. These functions of neutrophils are important in infections and vaccinations with adjuvants where neutrophils are abundant in the initial stages.
Peripheral blood natural killer cell count is associated with clinical outcome in patients with aaIPI 2–3 diffuse large B-cell lymphoma
Authors: A. Plonquet, C. Haioun, J.-P. Jais, A.-L. Debard, G. Salles, M.-C. Bene, P. Feugier, C. Rabian, O. Casasnovas, M. Labalette, E. Kuhlein, J.-P. Farcet, J.-F. Emile, C. Gisselbrecht, M.-H. Delfau-Larue
Journal: Annals of Oncology (2007)
Aetiological role of viral and bacterial infections in acute adult lower respiratory tract infection (LRTI) in primary care
Authors: D D Creer
Journal: Thorax (2005)

<b>Background:</b> Lower respiratory tract infections (LRTI) are a common reason for consulting general practitioners (GPs). In most cases the aetiology is unknown, yet most result in an antibiotic prescription. The aetiology of LRTI was investigated in a prospective controlled study. <b>Methods:</b> Eighty adults presenting to GPs with acute LRTI were recruited together with 49 controls over 12 months. Throat swabs, nasal aspirates (patients and controls), and sputum (patients) were obtained and polymerase chain reaction (PCR) and reverse transcriptase polymerase chain reaction (RT-PCR) assays were used to detect <i>Streptococcus pneumoniae</i>, <i>Mycoplasma pneumoniae</i>, <i>Chlamydia pneumoniae</i>, <i>Legionella pneumophila,</i> influenza viruses (AH1, AH3 and B), parainfluenza viruses 1–3, coronaviruses, respiratory syncytial virus, adenoviruses, rhinoviruses, and enteroviruses. Standard sputum bacteriology was also performed. Outcome was recorded at a follow up visit. <b>Results:</b> Potential pathogens were identified in 55 patients with LRTI (69%) and seven controls (14%; p&lt;0.0001). The identification rate was 63% (viruses) and 26% (bacteria) for patients and 12% (p&lt;0.0001) and 6% (p = 0.013), respectively, for controls. The most common organisms identified in the patients were rhinoviruses (33%), influenza viruses (24%), and <i>Streptococcus pneumoniae</i> (19%) compared with 2% (p&lt;0.001), 6% (p = 0.013), and 4% (p = 0.034), respectively, in controls. Multiple pathogens were identified in 18 of the 80 LRTI patients (22.5%) and in two of the 49 controls (4%; p = 0.011). Atypical organisms were rarely identified. Cases with bacterial aetiology were clinically indistinguishable from those with viral aetiology. <b>Conclusion:</b> Patients presenting to GPs with acute adult LRTI predominantly have a viral illness which is most commonly caused by rhinoviruses and influenza viruses.
Role of the <i>N</i>-Acetyltransferase 2 Detoxification System in Thyroid Cancer Susceptibility
Authors: Ana C.T. Guilhen, Natassia E. Bufalo, Elaine C. Morari, Janaina L. Leite, Ligia V.M. Assumpcao, Alfio J.A. Tincani, Laura S. Ward
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Genetic polymorphisms in genes encoding for enzymes involved in the biotransformation of carcinogens have been shown to be relevant as risk for cancer and may be of considerable importance from a public health point of view. Considering that N-acetyltransferase 2 (NAT2) polymorphisms modulate the response to ionizing radiation, the strongest risk factor recognized to cause differentiated thyroid cancer (DTC) thus far, we sought to determine the influence of NAT2 detoxification system on thyroid cancer susceptibility. Experimental Design: We conducted a prospective case-control study, comparing 195 patients presenting with DTC that were previously genotyped for GSTT1, GSTM1, GSTP1, and CYP1A1, comprising 164 papillary carcinomas and 31 follicular carcinomas, with 196 control individuals paired for gender, age, ethnicity, diet routine, lifetime occupational history, smoking history, general health conditions, and previous diseases. We used PCR-RFLP assays and the combination of 6 variant alleles to define 18 NAT2 haplotypes that characterized slow, intermediate, or rapid phenotypes. Results: A multivariate logistic regression analysis identified the presence of *12A and the absence of *12B, *13, *14B, *14D, *6A, and *7A NAT2 haplotypes as risk factors for DTC. The inheritance of a rapid acetylation phenotype doubled the risk for a papillary carcinoma (odds ratio, 2.024; 95% confidence interval, 1.252-3.272). We found no relationship between genotypes and clinical, pathologic, or laboratory features of patients or between genotypes and outcome. Conclusions: We showed that NAT2 genotypes and the NAT2 rapid acetylation phenotype are important susceptibility factors for DTC, suggesting that NAT2 detoxification system is involved in this tumor pathogenesis.
Toll-like receptor heterodimer variants protect from childhood asthma
Authors: Michael S.D. Kormann, Martin Depner, Dominik Hartl, Norman Klopp, Thomas Illig, Jerzy Adamski, Christian Vogelberg, Stephan K. Weiland, Erika von Mutius, Michael Kabesch
Journal: Journal of Allergy and Clinical Immunology (2008)
Both Metabolic Inhibition and Mitochondrial K <sub>ATP</sub> Channel Opening Are Myoprotective and Initiate a Compensatory Sarcolemmal Outward Membrane Current
Authors: Hiroshi Irie, Junyuan Gao, Glenn R. Gaudette, Ira S. Cohen, Richard T. Mathias, Adam E. Saltman, Irvin B. Krukenkamp
Journal: Circulation (2003)

Background— Blockade of oxidative phosphorylation may activate ATP sensitive mitochondrial potassium (mitoK ATP ) channels. We examined whether both metabolic inhibition and mitoK ATP channel openers protect both the whole organ and isolated cells from ischemia. Methods and Results— Using a Langendorff preparation, one group of isolated rabbit hearts were exposed to ischemic preconditioning (IPC) via 2 episodes of flow interruption. The second group of hearts was preconditioned with 2 episodes of either the metabolic inhibitor, sodium cyanide (NaCN), or the mitoK ATP channel opener, diazoxide. The third group of hearts was exposed to the mitoK ATP channel inhibitor, 5-hydroxydecanoic acid (5-HD) prior to preconditioning with NaCN, diazoxide or IPC. Controls had no drug infused. Then, ischemia was induced in all hearts by left anterior descending coronary artery occlusion and infarct size was determined. Compared with controls (40±3%), infarct size was significantly reduced in hearts preconditioned with NaCN, diazoxide or IPC (18±3%, 26±3%, 21±2%, respectively; P &lt;0.05 versus control). These reductions were reversed by 5-HD (36±3%, 33±2%, 37±2%; NaCN, diazoxide, IPC, respectively). Secondly, whole cell patch clamped isolated guinea pig ventricular myocytes were preconditioned with 2 episodes of either NaCN or diazoxide followed by Tyrodes perfusion with membrane potential set to −70 mV. Control cells were exposed to Tyrodes solution. All cells were then clamped to −20 mV and exposed to NaCN, which caused induction of an outward potassium current. Compared with controls, the average time to induction of the outward current was significantly reduced in cells preconditioned with either brief application of NaCN (11.6±1.8 versus 5.1±1.0 minutes, control versus NaCN, P &lt;0.05) or diazoxide (5.5±1.4 versus 2.0±0.8 minutes, control versus diazoxide, P &lt;0.05). Conclusion— Preconditioning protects the heart through mitoK ATP . This protection also alters a surface membrane current, which may be important in myocardial protection.
Preventing Excess Sun Exposure: It Is Time for a National Policy
Authors: K. M. Emmons, G. A. Colditz
Journal: JNCI Journal of the National Cancer Institute (1999)

It is now well established that childhood sun exposure is the primary risk factor for melanoma. The seminal observation linking age at exposure to risk was the finding that the incidence of melanoma increased among people who had migrated from northern latitudes to more equatorial latitudes but only among the immigrants who were children at the time of the migration (1–3). Individuals more than 15 years of age who emigrated from England and Ireland to Australia had substantially reduced risk of melanoma compared with those born in Australia. It has been confirmed that sunburns during childhood and adolescence are associated with an increased risk of melanoma (4). Lifetime exposure to ultraviolet radiation, including that incurred during adulthood, appears to play a major role in nonmelanoma skin cancer (5). To reduce the risk of both melanoma and nonmelanoma skin cancer, reduction of exposure to the sun throughout life is warranted. The article by Autier et al. (6) in this issue of the Journal raises important questions about the use of sunscreen to reduce the risk of skin cancer. Using a rigorous double-blind, randomized, controlled design, the authors observed that participants who received high sun-protection factor (SPF) sunscreen spent more time in the sun compared with those who received lower SPF sunscreen, despite the fact that all participants were blinded to the SPF formulation that they received. This finding may help us interpret previous epidemiologic studies (5) that have suggested that individuals who use sunscreen actually have higher rates of skin cancer than those who do not use sunscreen. It is likely that individuals whose skin type and/or genetic background place them at high risk for skin cancer have a propensity to burn when they are exposed to the sun and they are thus more likely to use sunscreen. The results of this trial add further evidence to the debate regarding recommendations for use of sunscreen. This trial suggests that the use of sunscreen alone will not lead to lower exposure but rather may result in longer time spent in the sun. Furthermore, study participants used only about one quarter the amount of sunscreen that is recommended for adequate coverage. This finding suggests that the increased skin cancer rates found among sunscreen users might also be associated with inadequate use of sunscreen. The results of this study may have a substantial impact on the public’s efforts regarding sun protection, particularly since sunscreen is widely considered by the public to provide adequate sun protection. Sunscreen use is the most common sun protection behavior currently performed in the United States, particularly by children (7). In considering the results of this study, it is important to remember that, until the second half of this century, sun exposure was avoided and at the beach clothing covered the
How Has the Age-Related Process of Overweight or Obesity Development Changed over Time? Co-ordinated Analyses of Individual Participant Data from Five United Kingdom Birth Cohorts
Authors: William Johnson, Leah Li, Diana Kuh, Rebecca Hardy
Journal: PLoS Medicine (2015)

Background There is a paucity of information on secular trends in the age-related process by which people develop overweight or obesity. Utilizing longitudinal data in the United Kingdom birth cohort studies, we investigated shifts over the past nearly 70 years in the distribution of body mass index (BMI) and development of overweight or obesity across childhood and adulthood. Methods and Findings The sample comprised 56,632 participants with 273,843 BMI observations in the 1946 Medical Research Council National Survey of Health and Development (NSHD; ages 2–64 years), 1958 National Child Development Study (NCDS; 7–50), 1970 British Cohort Study (BCS; 10–42), 1991 Avon Longitudinal Study of Parents and Children (ALSPAC; 7–18), or 2001 Millennium Cohort Study (MCS; 3–11). Growth references showed a secular trend toward positive skewing of the BMI distribution at younger ages. During childhood, the 50th centiles for all studies lay in the middle of the International Obesity Task Force normal weight range, but during adulthood, the age when a 50th centile first entered the overweight range (i.e., 25–29.9 kg/m2) decreased across NSHD, NCDS, and BCS from 41 to 33 to 30 years in males and 48 to 44 to 41 years in females. Trajectories of overweight or obesity showed that more recently born cohorts developed greater probabilities of overweight or obesity at younger ages. Overweight or obesity became more probable in NCDS than NSHD in early adulthood, but more probable in BCS than NCDS and NSHD in adolescence, for example. By age 10 years, the estimated probabilities of overweight or obesity in cohorts born after the 1980s were 2–3 times greater than those born before the 1980s (e.g., 0.229 [95% CI 0.219–0.240] in MCS males; 0.071 [0.065–0.078] in NSHD males). It was not possible to (1) model separate trajectories for overweight and obesity, because there were few obesity cases at young ages in the earliest-born cohorts, or (2) consider ethnic minority groups. The end date for analyses was August 2014. Conclusions Our results demonstrate how younger generations are likely to accumulate greater exposure to overweight or obesity throughout their lives and, thus, increased risk for chronic health conditions such as coronary heart disease and type 2 diabetes mellitus. In the absence of effective intervention, overweight and obesity will have severe public health consequences in decades to come.
Epilepsy in pregnancy and reproductive outcomes: a systematic review and meta-analysis
Authors: Luz Viale, John Allotey, Fiona Cheong-See, David Arroyo-Manzano, Dougall Mccorry, Manny Bagary, Luciano Mignini, Khalid S Khan, Javier Zamora, Shakila Thangaratinam
Journal: The Lancet (2015)
QT Dispersion as an Attribute of T-Loop Morphology
Authors: Jan A. Kors, Gerard van Herpen, Jan H. van Bemmel
Journal: Circulation (1999)

The suggestion that increased QT dispersion (QTD) is due to increased differences in local action potential durations within the myocardium is wanting. An alternative explanation was sought by relating QTD to vectorcardiographic T-loop morphology.The T loop is characterized by its amplitude and width (defined as the spatial angle between the mean vectors of the first and second halves of the loop). We reasoned that small, wide ("pathological") T loops produce larger QTD than large, narrow ("normal") loops. To quantify the relationship between QTD and T-loop morphology, we used a program for automated analysis of ECGs and a database of 1220 standard simultaneous 12-lead ECGs. For each ECG, QT durations, QTD, and T-loop parameters were computed. T-loop amplitude and width were dichotomized, with 250 microV (small versus large amplitudes) and 30 degrees (narrow versus wide loops) taken as thresholds. Over all 1220 ECGs, QTDs were smallest for large, narrow T loops (54.2+/-27.1 ms) and largest for small, wide loops (69. 5+/-33.5 ms; P<0.001).QTD is an attribute of T-loop morphology, as expressed by T-loop amplitude and width.
Free DNA and Carcinoembryonic Antigen Serum Levels: An Important Combination for Diagnosis of Colorectal Cancer
Authors: Emanuela Flamini, Laura Mercatali, Oriana Nanni, Daniele Calistri, Roberta Nunziatini, Wainer Zoli, Paola Rosetti, Nice Gardini, Arturo Lattuneddu, Giorgio Maria Verdecchia, Dino Amadori
Journal: Clinical Cancer Research (2006)

The identification of new molecular markers for the early detection of colorectal cancer has become an important objective. We compared the sensitivity and specificity of free circulating DNA with that of the more conventional carcinoembryonic antigen (CEA) and evaluated the two markers in combination.The study was carried out on 75 healthy donors and 75 colorectal cancer patients. Free DNA was determined in serum with quantitative PCR analysis. The diagnostic accuracy of each assay was calculated using receiver operating characteristic (ROC) curves. The diagnostic relevance of the two-marker combination was analyzed by the logistic regression model.Median free DNA concentration was approximately 5-fold higher in patients than in healthy donors (P < 0.001). The area under the ROC curve was 0.86, and when 12.5 ng/mL was used as cutoff, 81.3% sensitivity and 73.3% specificity were observed for the overall series. As CEA and free DNA provided independent diagnostic information, they were also considered in combination. ROC curve analysis of the combined CEA and free DNA algorithms showed a higher diagnostic capacity (area under the ROC curve, 0.92) than that of markers considered singly, with 84% sensitivity and 88% specificity.Free circulating DNA, especially when used in combination with CEA, represents a potentially useful tool for the diagnosis of early-stage colorectal cancer.
Human studies on genetics of the age at natural menopause: a systematic review
Authors: M. Voorhuis, N. C. Onland-Moret, Y. T. van der Schouw, B. C. J. M. Fauser, F. J. Broekmans
Journal: Human Reproduction Update (2010)

Timing of natural menopause has great implications for fertility and women's health. Age at natural menopause (ANM) is largely influenced by genetic factors. In the past decade, several genetic studies have been conducted to identify genes in ANM, which can help us unravel the biological pathways underlying this trait and the associated infertility and health risks. After providing an overview of the results of the genetic studies performed so far, we give recommendations for future studies in identifying genetic factors involved in determining the variation in timing of natural menopause. The electronic databases of Pubmed and Embase were systematically searched until September 2009 for genetic studies on ANM, using relevant keywords on the subject. Additional papers identified through hand search were also included. Twenty-eight papers emerged from our literature search. A number of genetic regions and variants involved in several possible pathways underlying timing of ANM were identified, including two possible interesting regions (9q21.3 and chromosome 8 at 26 cM) in linkage analyses. Recent genome-wide association studies have identified two genomic regions (19q13.42 and 20p12.3), containing two promising candidate genes (BRKS1 and MCM). In the candidate gene association studies on ANM, very few consistent associations were found. A number of genetic variants have been discovered in association with ANM, although the overall results have been rather disappointing. We have described possible new strategies for future genetic studies to identify more genetic loci involved in the variation in menopausal age.
Genomic structure of the gene for mouse germ-cell nuclear factor (GCNF). II. Comparison with the genomic structure of the human GCNF gene.
Authors: Ute Süsens, Uwe Borgmeyer
Journal: Genome biology (2001)

Germ-cell nuclear factor (GCNF, NR6AI) is an orphan nuclear receptor. Its expression pattern suggests it functions during embryogenesis, in the placenta and in germ-cell development. Mouse GCNF cDNA codes for a protein of 495 amino acids, whereas the four reported human cDNA variants code for proteins of 454 to 480 amino acids. Apart from this size difference, there is sequence conservation of up to 98.7%. To elucidate the genomic structure that gives rise to the different human GCNF mRNAs, the sequence information of the human GCNF locus is compared to the previously reported structure of the mouse locus.The genomic structures of the mouse and human GCNF genes are highly conserved. The comparison reveals that the shorter human protein results from skipping the 45 base-pair third exon. Three different human isoforms - GCNF-1, GCNF-2a and GCNF-2b - are generated by differential usage of alternative splice acceptor sites of the fourth and the seventh exon.By homology with the mouse gene, 11 GCNF coding exons can be defined on human chromosome 9. All human GCNF cDNAs identified so far are, however, derived from mRNAs generated by splicing the fourth to the second exon. Although the genomic sequence is highly conserved, the analysis suggests that alternative splicing generates a higher complexity of human GCNF isoforms compared with the situation in the mouse.