tbuckley/cabot-search huggingface dataset:
Overexpression of the Sarcolemmal Calcium Pump in the Myocardium of Transgenic Rats
Authors: Annette Hammes, Silke Oberdorf-Maass, Tobias Rother, Katja Nething, Frank Gollnick, Klaus W. Linz, Rainer Meyer, Kai Hu, Hong Han, Peter Gaudron, Georg Ertl, Sigrid Hoffmann, Ursula Ganten, Roland Vetter, Kai Schuh, Claudia Benkwitz, Hans G. Zimmer, Ludwig Neyses
Journal: Circulation Research (1998)

Abstract —The plasma membrane calmodulin–dependent calcium ATPase (PMCA) is a calcium-extruding enzyme controlling Ca 2+ homeostasis in nonexcitable cells. However, its function in the myocardium is unclear because of the presence of the Na + /Ca 2+ exchanger. We approached the question of the physiological function of the calcium pump using a transgenic “gain of function” model. Transgenic rat lines carrying the human PMCA 4 cDNA under control of the ventricle-specific myosin light chain-2 promoter were established, and expression in the myocardium was ascertained at the mRNA, protein, and functional levels. In vivo hemodynamic measurements in adult homozygous animals showed no differences in baseline and increased cardiac performance recruited by volume overload compared with controls. No differences between transgenic and control cardiomyocytes were found in patch clamp voltage dependence, activation/inactivation behavior of the L -type Ca 2+ current, or fast [Ca 2+ ] i transients (assessed by the Fura-2 method). To test whether the PMCA might be involved in processes other than beat-to-beat regulation of contraction/relaxation, we compared growth processes of neonatal transgenic and control cardiomyocytes. A 1.6- and 2.3-fold higher synthesis rate of total protein was seen in cells from transgenic animals compared with controls on incubation with 2% FCS for 24 hours and 36 hours, respectively. An effect of similar magnitude was observed using 20 μmol/L phenylephrine. A 1.4-fold– and 2.0-fold–higher protein synthesis peak was seen in PMCA-overexpressing cardiomyocytes after stimulation with isoproterenol for 12 hours and 24 hours, respectively. Because pivotal parts of the α- and β-adrenergic signal transduction pathways recently have been localized to caveolae, we tested the hypothesis that the PMCA might alter the amplitude of α- and β-adrenergic growth signals by virtue of its localization in caveolae. Biochemical as well as immunocytochemical studies suggested that the PMCA in large part was colocalized with caveolin 3 in caveolae of cardiomyocytes. These results indicate that the sarcolemmal Ca 2+ -pump has little relevance for beat-to-beat regulation of contraction/relaxation in adult animals but likely plays a role in regulating myocardial growth, possibly through modulation of caveolar signal transduction.
A Medical Review of Soviet Russia: IV.--Change in Type and Incidence of Disease
Authors: W. H. Gantt
Journal: BMJ (1926)

MODIFICATIONS in disease have taken place all over the civilized world as a result of the war, inifluenza pandemic, and social changes, but not on the same great scale as in the Union of Soviet Socialistic Republics (Russia).In no other country were the conditions so bad, and in Ino otlier country m-cre tiie chaniges in morbidity so enormous.Some diseases became epidemic, others remained unclhaniged, and a few disappeared altogether.We have been able to see in Russia the effects of war and fa.mine on all kinds of diseases-surgical, internal, nervous, etc.Some of these changes have beeni so remarkable, so little has been written about them (even in Russian, almost nnothing in English), that I have, durinig my two and a half years in Russia, collected these facts with a gi-eat deal of painis.An enormous number of originial MSS., official statistics, and Russian medical articles have been gone over for this purpose, and a certain amount of unpublished detail is included.The sources of information have been: a large number of original articles written by eminient Russian specialists in the various branclhes of medicine durinlg the faminie,
Breaks in Sedentary Time
Authors: Genevieve N. Healy, David W. Dunstan, Jo Salmon, Ester Cerin, Jonathan E. Shaw, Paul Z. Zimmet, Neville Owen
Journal: Diabetes Care (2008)

Total sedentary (absence of whole-body movement) time is associated with obesity, abnormal glucose metabolism, and the metabolic syndrome. In addition to the effects of total sedentary time, the manner in which it is accumulated may also be important. We examined the association of breaks in objectively measured sedentary time with biological markers of metabolic risk.Participants (n = 168, mean age 53.4 years) for this cross-sectional study were recruited from the 2004-2005 Australian Diabetes, Obesity and Lifestyle study. Sedentary time was measured by an accelerometer (counts/minute(-1) < 100) worn during waking hours for seven consecutive days. Each interruption in sedentary time (counts/min > or = 100) was considered a break. Fasting plasma glucose, 2-h plasma glucose, serum triglycerides, HDL cholesterol, weight, height, waist circumference, and resting blood pressure were measured. MatLab was used to derive the breaks variable; SPSS was used for the statistical analysis.Independent of total sedentary time and moderate-to-vigorous intensity activity time, increased breaks in sedentary time were beneficially associated with waist circumference (standardized beta = -0.16, 95% CI -0.31 to -0.02, P = 0.026), BMI (beta = -0.19, -0.35 to -0.02, P = 0.026), triglycerides (beta = -0.18, -0.34 to -0.02, P = 0.029), and 2-h plasma glucose (beta = -0.18, -0.34 to -0.02, P = 0.025).This study provides evidence of the importance of avoiding prolonged uninterrupted periods of sedentary (primarily sitting) time. These findings suggest new public health recommendations regarding breaking up sedentary time that are complementary to those for physical activity.
Reassessing the role of QTc in the diagnosis of autonomic failure among patients with diabetes: a meta-analysis.
Authors: E A Whitsel, E J Boyko, D S Siscovick
Journal: Diabetes Care (2000)

A 1992 consensus statement on autonomic testing portrayed Bazett's heart rate-corrected QT interval (QT) prolongation as a specific yet insensitive indicator of diabetic autonomic failure. At that time, only a few small studies had evaluated the accuracy of QTc. To date, even fewer studies have evaluated whether its accuracy is influenced by patient characteristics.We critically appraised 17 studies reporting the sensitivity and specificity of QTc for diabetic autonomic failure. The studies represented 4,584 patients with diabetes (mean age 34.9 years, 46% female, 92% with type 1 diabetes, mean duration of diabetes 14.5 years). We summarized the accuracy of QTc prolongation for diabetic autonomic failure as an odds ratio (OR) (95% CI) and determined whether patient and study design characteristics influenced the accuracy of QTc prolongation by comparing summary receiver operating characteristic curves.Autonomic failure, defined as > or =1.2+/-0.4 (mean +/- SD) abnormal of 2.0+/-1.6 administered cardiovascular reflex tests, was found in 26% (25-28) of patients. The pooled sensitivity and specificity of QTc > 441+/-8 ms for autonomic failure were 28% (26-29) and 86% (85-87), respectively. Autonomic failure was 2.26 times (1.90-2.70) more likely to be present in patients with than in patients without QTc prolongation. At 86% specificity, the sensitivity of QTc prolongation was 46 vs. 12% for men versus women (P = 0.0077), respectively, and, after adjustment for sex, 66 vs. 17% among patients aged 25 vs. 55 years (P = 0.1902) and 61 vs. 27% at thresholds of >420 vs. >460 ms, respectively (P = 0.2964).QTc prolongation is a specific albeit insensitive indicator of autonomic failure. Although QTc prolongation is relatively accurate for men, accuracy may be even greater for young men at low QTc thresholds.
Infantile eczema: Prognosis and risk of asthma and rhinitis in preadolescence
Authors: Natalia Ballardini, Anna Bergström, Maria Böhme, Marianne van Hage, Eva Hallner, Emma Johansson, Cilla Söderhäll, Inger Kull, Magnus Wickman, Carl-Fredrik Wahlgren
Journal: Journal of Allergy and Clinical Immunology (2013)
Trends in Survival after In-Hospital Cardiac Arrest
Authors: Saket Girotra, Brahmajee K. Nallamothu, John A. Spertus, Yan Li, Harlan M. Krumholz, Paul S. Chan
Journal: New England Journal of Medicine (2012)

Despite advances in resuscitation care in recent years, it is not clear whether survival and neurologic function after in-hospital cardiac arrest have improved over time.
Circulating microRNAs as biomarkers - True Blood?
Authors: Nathalie Schöler, Christian Langer, Florian Kuchenbauer
Journal: Genome Medicine (2011)

MicroRNAs are post-transcriptional regulators that are involved in many physiological and pathophysiological conditions. A recent study compared the expression profiles of hundreds of blood-borne microRNAs across a variety of nonmalignant and malignant diseases to identify disease-specific expression patterns. The resulting microRNA expression data could be used to discriminate disease samples with a high level of accuracy, demonstrating the potential for using microRNA signatures for the blood-based diagnosis of disease.
Autotaxin Production of Lysophosphatidic Acid Mediates Allergic Asthmatic Inflammation
Authors: Gye Young Park, Yong Gyu Lee, Evgeny Berdyshev, Sharmilee Nyenhuis, Jian Du, Panfeng Fu, Irina A. Gorshkova, Yongchao Li, Sangwoon Chung, Manjula Karpurapu, Jing Deng, Ravi Ranjan, Lei Xiao, H. Ari Jaffe, Susan J. Corbridge, Elizabeth A. B. Kelly, Nizar N. Jarjour, Jerold Chun, Glenn D. Prestwich, Eleanna Kaffe, Ioanna Ninou, Vassilis Aidinis, Andrew J. Morris, Susan S. Smyth, Steven J. Ackerman, Viswanathan Natarajan, John W. Christman
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Rationale: Bioactive lipid mediators, derived from membrane lipid precursors, are released into the airway and airspace where they bind high-affinity cognate receptors and may mediate asthma pathogenesis. Lysophosphatidic acid (LPA), a bioactive lipid mediator generated by the enzymatic activity of extracellular autotaxin (ATX), binds LPA receptors, resulting in an array of biological actions on cell proliferation, migration, survival, differentiation, and motility, and therefore could mediate asthma pathogenesis.Objectives: To define a role for the ATX-LPA pathway in human asthma pathogenesis and a murine model of allergic lung inflammation.Methods: We investigated the profiles of LPA molecular species and the level of ATX exoenzyme in bronchoalveolar lavage fluids of human patients with asthma subjected to subsegmental bronchoprovocation with allergen. We interrogated the role of the ATX-LPA pathway in allergic lung inflammation using a murine allergic asthma model in ATX-LPA pathway–specific genetically modified mice.Measurements and Main Results: Subsegmental bronchoprovocation with allergen in patients with mild asthma resulted in a remarkable increase in bronchoalveolar lavage fluid levels of LPA enriched in polyunsaturated 22:5 and 22:6 fatty acids in association with increased concentrations of ATX protein. Using a triple-allergen mouse asthma model, we showed that ATX-overexpressing transgenic mice had a more severe asthmatic phenotype, whereas blocking ATX activity and knockdown of the LPA2 receptor in mice produced a marked attenuation of Th2 cytokines and allergic lung inflammation.Conclusions: The ATX-LPA pathway plays a critical role in the pathogenesis of asthma. These preclinical data indicate that targeting the ATX-LPA pathway could be an effective antiasthma treatment strategy.
Conditional BRAFV600E Expression Induces DNA Synthesis, Apoptosis, Dedifferentiation, and Chromosomal Instability in Thyroid PCCL3 Cells
Authors: Norisato Mitsutake, Jeffrey A. Knauf, Shin Mitsutake, Cleo Mesa, Lei Zhang, James A. Fagin
Journal: Cancer Research (2005)

Abstract The activating mutation BRAFT1796A is the most prevalent genetic alteration in papillary thyroid carcinomas (PTC). It is associated with advanced PTCs, suggesting that this oncoprotein confers thyroid cancers with more aggressive properties. BRAFT1796A is also observed in thyroid micropapillary carcinomas and may thus be an early event in tumor development. To explore its biological consequences, we established doxycycline-inducible BRAFV600E-expressing clonal lines derived from well-differentiated rat thyroid PCCL3 cells. Expression of BRAFV600E did not induce growth in the absence of thyrotropin despite increasing DNA synthesis, which is likely explained because of a concomitant increase in apoptosis. Thyrotropin-dependent cell growth and DNA synthesis were reduced by BRAFV600E because of decreased thyrotropin responsiveness associated with inhibition of thyrotropin receptor gene expression. These results are similar to those obtained following conditional expression of RET/PTC. However, in contrast to RET/PTC, BRAF activation did not impair key activation steps distal to the thyrotropin receptor, such as forskolin-induced adenylyl cyclase activity or cyclic AMP–induced DNA synthesis. We reported previously that acute RET/PTC expression in PCCL3 cells did not induce genomic instability. By contrast, induction of BRAFV600E expression increased the frequency of micronuclei by both clastogenic and aneugenic events. These data indicate that BRAFV600E expression confers thyroid cells with little growth advantage because of concomitant activation of DNA synthesis and apoptosis. However, in contrast to RET/PTC, BRAFV600E may facilitate the acquisition of secondary genetic events through induction of genomic instability, which may account for its aggressive properties.
Subthreshold concentration of endothelin-1-enhanced, capsaicin-induced bronchoconstriction in anaesthetized guinea-pigs
Authors: H Kanazawa, H Fujiwara, K Hirata, J Yoshikawa
Journal: European Respiratory Journal (1998)

An increasing number of studies have been performed to address a possible role for endothelin-1 (ET-1) as a significant mediator in asthma. However, the effects of subthreshold concentrations of ET-1, which cannot elicit bronchial smooth muscle contraction itself, in asthma has yet to be determined. This study determined these effects of ET-1 on capsaicin-induced bronchoconstriction in anaesthetized guinea-pigs. Aerosolized ET-1 administered at doses of 10(-9) M and higher induced a dose-dependent increase in pulmonary resistance, but ET-1 at 10(-10) M did not have any bronchoconstrictive effect. However, this subthreshold concentration of ET-1 potentiated capsaicin-induced bronchoconstriction. In addition, the potentiation of capsaicin-induced bronchoconstriction by this subthreshold concentration of ET-1 was completely abolished by BQ788 (ET(B) receptor antagonist), but not BQ123 (ET(A) receptor antagonists). Immunoreactive substance P (SP) levels in bronchoalveolar lavage fluid after capsaicin administration were significantly higher than those after solvent administration. However, ET-1 alone did not significantly stimulate immunoreactive SP release and ET-1 (10(-10) M) did not potentiate capsaicin-induced immunoreactive SP release. In contrast, ET-1 (10(-10) M) potentiated exogenous neurokinin A- and SP-induced bronchoconstriction. These findings suggest that a subthreshold concentration of endothelin-1 does not potentiate the tachykinin release induced by capsaicin but the airway smooth muscle contraction through endothelin-B receptors.
Phosphorylation of Histone H2B at DNA Double-Strand Breaks
Authors: Oscar Fernandez-Capetillo, C. David Allis, André Nussenzweig
Journal: The Journal of Experimental Medicine (2004)

Posttranslational modifications of histone tails regulate numerous biological processes including transcription, DNA repair, and apoptosis. Although recent studies suggest that structural alterations in chromatin are critical for triggering the DNA damage response, very little is known about the nature of DNA damage-induced chromatin perturbations. Here we show that the serine 14 residue in the NH2-terminal tail of histone H2B is rapidly phosphorylated at sites of DNA double-strand breaks. At late time points after irradiation, the phosphorylated form of H2B, H2B-Ser14P, accumulates into irradiation-induced foci. H2B-Ser14P foci formation is not associated with the apoptotic phosphorylation of H2B but is strictly dependent on the phosphorylated isoform of H2AX. Our results broaden the spectrum of histone modifications that constitute the DNA damage “histone code” and suggest a model for the underlying chromatin structure within damage-induced foci.
Decreased glucose effectiveness but not insulin resistance in glucose-tolerant offspring of Japanese non—insulin-dependent diabetic patients: A minimal-model analysis
Authors: Kentaro Doi, Ataru Taniguchi, Yoshikatsu Nakai, Hitomi Kawamura, Yasuki Higaki, Hideki Yokoi, Hiroaki Tanaka, Junzo Fujitani, Masashige Suzuki, Kumpei Tokuyama, Masahiko Sakai, Mitsuo Fukushima
Journal: Metabolism (1997)
Clinicopathologic Features of &lt;EMPH TYPE="ITAL"&gt;BRCA&lt;/EMPH&gt;-Linked and Sporadic Ovarian Cancer
Authors: Jeff Boyd
Journal: JAMA (2000)

Context Most hereditary ovarian cancers are associated with germline mutations in BRCA1 or BRCA2.Attempts to define the clinical significance of BRCA mutation status in ovarian cancer have produced conflicting results, especially regarding survival.Objective To determine whether hereditary ovarian cancers have distinct clinical and pathological features compared with sporadic (nonhereditary) ovarian cancers. Design and SettingRetrospective cohort study of a consecutive series of 933 ovarian cancers diagnosed and treated at our institution, which is a comprehensive cancer center as designated by the National Cancer Institute, over a 12-year period (December 1986 to August 1998).
Multiepitope CD8+ T cell response to a NY-ESO-1 peptide vaccine results in imprecise tumor targeting
Authors: Valérie Dutoit, Robert N. Taub, Kyriakos P. Papadopoulos, Susan Talbot, Mary-Louise Keohan, Michelle Brehm, Sacha Gnjatic, Paul E. Harris, Brygida Bisikirska, Philippe Guillaume, Jean-Charles Cerottini, Charles S. Hesdorffer, Lloyd J. Old, Danila Valmori
Journal: Journal of Clinical Investigation (2002)

The cancer-testis antigen NY-ESO-1 is one of the most promising candidates for generic vaccination of cancer patients. Here we analyzed the CD8+ T cell response to a NY-ESO-1 peptide vaccine composed of the two previously defined peptides 157-165 and 157-167, administered with GM-CSF as a systemic adjuvant. The NY-ESO-1 peptide vaccine elicited a CD8+ T cell response directed against multiple distinct epitopes in the 157-167 region, as revealed by using A2/peptide multimers incorporating overlapping A2 binding peptides in this region. However, only a minor fraction of the elicited CD8+ T cells, namely those recognizing the peptide 157-165 with sufficiently high functional avidity, recognized the naturally processed target on NY-ESO-1+ tumor cells. In contrast, the majority of peptide 157-165–specific CD8+ T cells exhibited lower functional avidity and no tumor reactivity. In addition, vaccine-elicited CD8+ T cells specific for other overlapping epitopes in the 157-167 region failed to significantly recognize NY-ESO-1–expressing tumor targets. Thus, because of the complexity of the CD8+ T cell repertoire that can be elicited by vaccination with synthetic peptides, a precise definition of the targeted epitope, and hence, of the corresponding peptide to be used as immunogen, is required to ensure a precise tumor targeting.
Pulmonary puzzle: a precordial crunch
Authors: Edward B G Barnard, Joanna Rimmer, Andrew McD Johnston
Journal: Thorax (2013)

Three patients with unusual additional sounds heard on auscultation of the precordium were admitted to a military hospital in Afghanistan.

Patient 1 : A male in his 20s was shot in his left flank. Injuries included a left haemothorax and visceral injuries. An intercostal drain (ICD) was inserted. After surgery, he was admitted to the intensive care unit (ICU) where a ‘click’ was heard on auscultation of the precordium just after the second heart sound, loudest in expiration. A chest radiograph was taken (figure 1).



Figure 1 
A chest radiograph of patient 1.



Patient 2 : A male in his 20s was very close to an explosion. He had fragmentation wounds to his chest, abdomen and limbs. Initial CT scan demonstrated …
Influence of the degree of liver failure on systemic and splanchnic haemodynamics and on response to propranolol in patients with cirrhosis.
Authors: A Braillon, P Cales, D Valla, D Gaudy, P Geoffroy, D Lebrec
Journal: Gut (1986)

Systemic and splanchnic haemodynamics were studied in patients with cirrhosis who had been classified in three groups (A, B, and C) according to the degree of liver failure (modified Pugh9s classification). In patients of group A, cardiac index was significantly lower than that of group C and systemic vascular resistance was higher, but not significantly so, than that of patients with liver failure. Wedged hepatic venous pressure was significantly lower in the former group than in the latter. In patients in group B, corresponding values fell between those of groups A and C. Azygos blood flow averaged 0.477 +/- 0.242 l/min (mean +/- SD) in group A and it was significantly lower than in groups B and C (0.642 +/- 0.224 and 1.061 +/- 0.476 l/min, respectively). In the three groups, acute administration of propranolol induced statistically significant changes in systemic and splanchnic haemodynamics. In patients of group C but not of group B, the mean value of azygos blood flow after propranolol remained significantly higher than in group A. Moreover, the fraction of azygos blood flow to cardiac output decreased in groups A and B while slightly increased in group C. This study shows that in patients with cirrhosis, the degree of liver failure may be a determinant for the haemodynamic responses to drugs acting on portal hypertension.
Colorectal cancer surveillance in inflammatory bowel disease: a primary care perspective
Authors: E. A. Arthurs, K. Burley, B. Gholkar, L. Williams, M. Lockett
Journal: Gut (2011)

<h3>Introduction</h3> Patients with colitis are at increased risk of colorectal cancer (CRC). The British Society of Gastroenterology (BSG) has been advocating colonoscopic surveillance to detect dysplasia and early CRC since 20021. The aim is to assess whether patients with inflammatory bowel disease (IBD) in primary care have been receiving appropriate surveillance for CRC according to the BSG guidelines (2002). <h3>Methods</h3> Three GP practices were audited. Patients with IBD were identified from primary care computerised records by searching for IBD, Crohn9s disease, ulcerative, indeterminate and distal colitis and proctitis. Cases were verified by paper records. Data regarding diagnosis, date of symptom onset, disease extent and CRC surveillance was collected and analysed. Individualised recommendations were made according to the current BSG guidelines for CRC surveillance. A detailed report was given to the primary care practice, and patients not known to secondary care were added to the North Bristol NHS Trust IBD database. <h3>Results</h3> 166 patients were identified with IBD from 29 054 patients. 100 patients (60.2%) had colitis extent requiring surveillance. 59 patients (59%) had symptom onset &gt;10 years; 10 patients (16.9%) had undergone colonoscopy at 8–10 years, 19 (32.2%) had not and 6 (10.2%) are due in 2010. 11 (18.6%) had an unknown extent of disease but no clear surveillance, and 13 (22%) had no record of any colonoscopy within their notes. Of 59 patients, 37 (62.7%) were eligible for repeat colonoscopy; 3 (8.1%) had undergone this, 27 (72.9%) had not and in 7 (18.9%) it was unclear from records. <h3>Conclusion</h3> Records in the practices we audited were unclear and incomplete, but it appears that patients with IBD in primary care are not receiving appropriate CRC surveillance. This emphasises the need for a reliable surveillance programme with established links with secondary care.