tbuckley/cabot-search huggingface dataset:
Absence of Malonyl Coenzyme A Decarboxylase in Mice Increases Cardiac Glucose Oxidation and Protects the Heart From Ischemic Injury
Authors: Jason R.B. Dyck, Teresa A. Hopkins, Sebastien Bonnet, Evangelos D. Michelakis, Martin E. Young, Miho Watanabe, Yosuke Kawase, Kou-ichi Jishage, Gary D. Lopaschuk
Journal: Circulation (2006)

Acute pharmacological inhibition of cardiac malonyl coenzyme A decarboxylase (MCD) protects the heart from ischemic damage by inhibiting fatty acid oxidation and stimulating glucose oxidation. However, it is unknown whether chronic inhibition of MCD results in altered cardiac function, energy metabolism, or ischemic cardioprotection.Mcd-deficient mice were produced and assessed for in vivo cardiac function as well as ex vivo cardiac function, energy metabolism, and ischemic tolerance. In vivo and ex vivo cardiac function was similar in wild-type and mcd-/- mice. Ex vivo working hearts from mcd-/- and wild-type mice displayed no significant differences in rates of fatty acid oxidation, glucose oxidation, or glycolysis. However, cardiac deletion of mcd resulted in an increased expression of genes regulating fatty acid utilization that may compensate for the loss of MCD protein and likely contributes to the absence of changes in energy metabolism in the aerobic heart. Despite the lack of changes in fatty acid utilization, hearts from mcd-/- mice displayed a marked preference for glucose utilization after ischemia, which correlated with a significant cardioprotection of ischemic hearts from mcd-/- mice compared with wild-type mice.Deletion of MCD markedly increases glucose oxidation and improves functional recovery of the heart after ischemia. As a result, chronic pharmacological inhibition of MCD may be a viable approach to treat myocardial ischemia.
Abnormal diurnal variation of blood pressure, cardiac output, and vascular resistance in cardiac transplant recipients.
Authors: R N Idema, A H van den Meiracker, A H Balk, E Bos, M A Schalekamp, A J Man in 't Veld
Journal: Circulation (1994)

An attenuated or absent nocturnal decline in blood pressure has repeatedly been documented in cardiac transplant recipients. The present study was aimed at investigating the hemodynamic mechanism underlying this abnormality.In 23 cardiac transplant recipients (11 to 36 months after transplantation) and in 23 control subjects matched for age and 24-hour mean arterial pressure, invasive 24-hour ambulatory blood pressure was measured by means of the Oxford technique. Beat-to-beat relative values of stroke volume were determined by means of a pulse-contour method, and relative changes of cardiac output (stroke volume x heart rate) and total peripheral vascular resistance (blood pressure/cardiac output) over the 24-hour period were calculated. The nocturnal decline in blood pressure was 20 +/- 8% (mean +/- SD) in control subjects but only 5 +/- 9% (P < .001) in cardiac transplant recipients. In control subjects, the nocturnal decline in blood pressure was associated with a nocturnal fall in cardiac output of 24 +/- 13%, whereas vascular resistance compared with daytime value did not change. The small nocturnal decline in blood pressure in cardiac transplant recipients was associated with an attenuated nocturnal fall in cardiac output of 14 +/- 12% (P < .05 versus control subjects). In addition, vascular resistance compared with daytime value was increased by 9 +/- 9% (P < .05) during the night. Both in cardiac transplant recipients and in control subjects, the nocturnal changes in blood pressure were correlated with the nocturnal changes in cardiac output but not with the nocturnal changes in total peripheral vascular resistance.This study confirms the attenuated nocturnal fall in blood pressure in cardiac transplant recipients. Hemodynamically, this attenuated blood pressure decline is characterized by a reduced nocturnal fall in cardiac output, and it is associated with a nocturnal increase in vascular resistance.
VEGF-Mediated Angiogenesis Links EMT-Induced Cancer Stemness to Tumor Initiation
Authors: Anna Fantozzi, Dorothea C. Gruber, Laura Pisarsky, Chantal Heck, Akiko Kunita, Mahmut Yilmaz, Nathalie Meyer-Schaller, Karen Cornille, Ulrike Hopfer, Mohamed Bentires-Alj, Gerhard Christofori
Journal: Cancer Research (2014)

Abstract An epithelial–mesenchymal transition (EMT) underlies malignant tumor progression and metastatic spread by enabling cancer cells to depart from the primary tumor, invade surrounding tissue, and disseminate to distant organs. EMT also enriches for cancer stem cells (CSC) and increases the capacity of cancer cells to initiate and propagate tumors upon transplantation into immune-deficient mice, a major hallmark of CSCs. However, the molecular mechanisms promoting the tumorigenicity of cancer cells undergoing an EMT and of CSCs have remained widely elusive. We here report that EMT confers efficient tumorigenicity to murine breast cancer cells by the upregulated expression of the proangiogenic factor VEGF-A and by increased tumor angiogenesis. On the basis of these data, we propose a novel interpretation of the features of CSCs with EMT-induced, VEGF-A–mediated angiogenesis as the connecting mechanism between cancer cell stemness and tumor initiation. Cancer Res; 74(5); 1566–75. ©2014 AACR.
Autophagocytosis of the apical membrane in microvillus inclusion disease
Authors: Reinshagen K, Naim Hy, Zimmer Kp
Journal: Gut (2002)

Microvillus inclusion disease (MID) is a disorder with the clinical signs of intractable diarrhoea in the newborn and infancy. The typical pathological features of the disease are well known whereas the pathophysiology is still unclear.This study was performed to define possible alterations of the cytoskeleton and exocytic as well as endocytic pathways within enterocytes in MID.Four patients with MID were studied. Three had a congenital onset of diarrhoea and one patient had a late onset form.Thin frozen sections of small bowel biopsies of patients were labelled by antibodies against the cytoskeleton and the brush border enzyme sucrase-isomaltase. The binding sites of the primary antibodies were visualised by immunogold particles in the electron microscope. Biopsies were labelled in organ culture to analyse the biosynthetic and endocytic pathways within the enterocytes.Labelling with antibodies against actin and villin did not differ significantly in control and patient biopsies. Biosynthetic labelling revealed normal intracellular processing and transport of the brush border enzyme sucrase-isomaltase. Secretory granules in crypt epithelial cells were positive for sucrase-isomaltase, differing in its labelling density between patients. Patient biopsies showed microvillus inclusion bodies which endocytosed cationised ferritin within five minutes after uptake as well as ovalbumin after incubation for 10 minutes. These microvillus inclusion bodies correspond to early endosomes because they lack lysosome associated membrane proteins. Late endosomes and lysosomes containing sucrase-isomaltase did not reveal microvillus-like structures.Microvillus inclusion bodies in MID originate from autophagocytosis of the apical membrane of enterocytes with engulfing of microvilli.
Challenges in pulmonary fibrosis {middle dot} 4: Smoking-induced diffuse interstitial lung diseases
Authors: A. U Wells, A. G Nicholson, D. M Hansell
Journal: Thorax (2007)

Smoking-induced diffuse interstitial lung processes include respiratory bronchiolitis, respiratory bronchiolitis-associated interstitial lung disease (RBILD), desquamative interstitial pneumonia (DIP) and Langerhans' cell histiocytosis. The histological, radiological and clinical features of respiratory bronchiolitis, RBILD and DIP are reviewed, with particular reference to management issues; Langerhans' cell histiocytosis is covered elsewhere in this series of articles. Possible relationships between smoking and other diffuse lung diseases are explored briefly.
Inhibition of collagen-induced platelet aggregation by normal plasma
Authors: H. L. Nossel, G. D. Wilner, M. Drillings
Journal: Journal of Clinical Investigation (1971)

Normal plasma has been found to inhibit the platelet aggregation-inducing effect of collagen in a time consuming reaction independent of temperature. Collagen treated with serum and washed has reduced reactivity which can be restored to normal by treatment with 1.5 M sodium chloride. On the basis of this result, it is suggested that inhibition results from adsorption to collagen of a plasma component. The inhibitory plasma component is destroyed at 56 degrees C, is unstable below pH 7, and migrates with the alpha globulins on starch block electrophoresis at pH 8.6. On the basis of ultrafiltration and sucrose density gradient ultracentrifugation studies, a molecular weight in the range of 330,000 is suggested and there may be an additional component of considerably greater size. Partial purification can be achieved by ion exchange chromatography. The purified fraction was completely inactivated by incubation with trypsin. Partially purified fractions inhibit cationic platelet aggregators such as collagen, polylysine, and hexadimethrine but do not affect anionic aggregators such as succinylated collagen and sodium stearate. Normal plasma and serum inhibit succinylated collagen and stearate. Stearate is inhibited by crystalline albumin and Cohn fraction IV-4. It is suggested that plasma proteins may regulate platelet adhesion to collagen and other vessel wall materials.
Exposure to substances in the workplace and new-onset asthma: an international prospective population-based study (ECRHS-II)
Authors: Manolis Kogevinas, Jan-Paul Zock, Debbie Jarvis, Hans Kromhout, Linnéa Lillienberg, Estel Plana, Katja Radon, Kjell Torén, Ada Alliksoo, Geza Benke, Paul D Blanc, Anna Dahlman-Hoglund, Angelo D'Errico, Michel Héry, Susan Kennedy, Nino Kunzli, Bénédicte Leynaert, Maria C Mirabelli, Nerea Muniozguren, Dan Norbäck, Mario Olivieri, Félix Payo, Simona Villani, Marc van Sprundel, Isabel Urrutia, Gunilla Wieslander, Jordi Sunyer, Josep M Antó
Journal: The Lancet (2007)
CpG Islands as a Putative Source for Animal miRNAs: Evolutionary and Functional Implications
Authors: D. Dahary, R. Shalgi, Y. Pilpel
Journal: Molecular Biology and Evolution (2010)

MicroRNAs (miRs) are considered major contributors to the evolution of animal morphological complexity. Multiple bursts of novel miR families were documented throughout animal evolution, yet, their evolutionary origins are not understood. Here, we discuss two alternative genomic sources for novel miR families, namely, transposable elements, which were previously described, and a newly proposed origin: CpG islands. We show that these two origins are evolutionarily distinct and that they correspond to marked differences in several functional and genomic characteristics. Together, our results shed light on the intriguing origin of one of the major constituents of regulatory networks in animals, miRs.
Redistribution of Myosin VI from Top to Base of Proximal Tubule Microvilli during Acute Hypertension
Authors: Li E. Yang, Arvid B. Maunsbach, Patrick K.K. Leong, Alicia A. McDonough
Journal: Journal of the American Society of Nephrology (2005)

During acute hypertension, Na(+)/H(+) exchangers (NHE3) retract from top to base of proximal tubule microvilli (MV) and Na(+) reabsorption decreases in proximal tubule. This study aimed to determine whether the actin-based motor myosin VI coordinately retracts with NHE3 in response to acute hypertension. BP was raised approximately 50 mmHg in rats for 20 to 30 min or sham treated, and kidneys were analyzed by subcellular fractionation or microscopy. During acute hypertension, myosin VI redistributed from low density apical MV-enriched membranes (from 23 +/- 2.4 to 11.4 +/- 2.2%) into higher density membranes (from 23.2 +/- 0.7 to 36.9 +/- 2.6%). By confocal microscopy, myosin VI was detected over the whole length of the MV in controls, then became completely focused at the base of MV during acute hypertension. For electron microscopic analysis using immunogold labeling, MV were divided into five zones from top (z1) to base (z5). In controls, myosin VI was evenly distributed through the five MV zones. In acute hypertension, myosin VI decreased in z1 (from 20.6 +/- 1.9 to 10.5 +/- 2.3%) and z2 (from 21.0 +/- 2.0 to 13.2 +/- 1.4%) and increased in z5 (from 21.1 +/- 3.3 to 38.6 +/- 3.0%). These results provide the first observation that acute hypertension causes myosin VI redistribution and support the idea that myosin VI may serve as the molecular motor for NHE3 retraction from top to base of MV during acute hypertension.
P55 Should Initial Lung Cancer Staging Include the Pelvis?
Authors: DM Komrower, G Jones, N Hunt, M Murthy, M Ledson, MJ Walshaw
Journal: Thorax (2013)

<h3>Introduction</h3> Current NICE guidance indicates that lung cancer should be staged by a contrast enhanced chest CT scan which includes the liver and adrenals, and to look for distant metastases those with potentially curable disease should be offered PET-CT scanning. However, the latter is expensive and limited in availability, and it has been suggested that including the pelvic area in the staging CT scan might obviate the need (Botchua <i>et al</i> 2012). We looked at 284 PET-CT scans performed for the staging of lung cancer in our unit to test this further. <h3>Method</h3> We selected all PET-CT scans that showed distant metastases (and therefore upstaged the disease) for further scrutiny. In those where pelvic deposits were visible on the PET component, the CT element was reviewed to establish whether the diagnosis of pelvic metastases could have been made by CT scan alone. <h3>Results</h3> 23 PET-CT scans (8.1%) identified distant metastatic disease, in 3 (1.1%) cases in the pelvic area. Of these, 2 had bony metastases that were visible on the CT element of the scan: in the remaining case the PET element demonstrated increased uptake around a joint replacement and CT component demonstrated a pathological fracture. <h3>Conclusion</h3> This study has shown that if the pelvic area was included in the CT staging scan for lung cancer, in our cohort of 284 patients, only 3 (1.1%) would not have required a subsequent PET scan. In the remaining patients, the additional burden of pelvic CT in terms of radiation exposure and financial expense cannot be justified and therefore we do not recommend that the protocol for a staging CT scan in lung cancer is altered to include the pelvis.
Preceding infection as an important risk factor for ischaemic brain infarction in young and middle aged patients
Authors: J. Syrjanen, V. V Valtonen, M. Iivanainen, M. Kaste, J. K Huttunen
Journal: BMJ (1988)

The role of preceding infection as a risk factor for ischaemic stroke was investigated in a case-control study of 54 consecutive patients under 50 years of age with brain infarction and 54 randomly selected controls from the community matched for sex and age. Information about previous illnesses, smoking, consumption of alcohol, and use of drugs was taken. A blood sample was analysed for standard biochemical variables and serum cholesterol, high density lipoprotein cholesterol, triglyceride, and fasting blood glucose concentrations determined. Titres of antimicrobial antibodies against various bacteria, including Staphylococcus, Streptococcus, Yersinia, and Salmonella and several viruses were determined. Febrile infection was found in patients during the month before the brain infarction significantly more often than in controls one month before their examination (19 patients v three controls; estimated relative risk 9.0 (95% confidence interval 2.2 to 80.0)). The most common preceding febrile infection was respiratory infection (80%). Infections preceding brain infarction were mostly of bacterial origin based on cultural, serological, and clinical data. In conditional logistic regression analysis for matched pairs the effect of preceding febrile infection remained significant (estimated relative risk 14.5 (95% confidence interval 1.9 to 112.3)) when tested with triglyceride concentration, hypertension, smoking, and preceding intoxication with alcohol. Although causality cannot be inferred from these data and plausible underlying mechanisms remain undetermined, preceding febrile infection may play an important part in the development of brain infarction in young and middle aged patients.
A Randomized Study Comparing Same-Day Home Discharge and Abciximab Bolus Only to Overnight Hospitalization and Abciximab Bolus and Infusion After Transradial Coronary Stent Implantation
Authors: Olivier F. Bertrand, Robert De Larochellière, Josep Rodés-Cabau, Guy Proulx, Onil Gleeton, Can Manh Nguyen, Jean-Pierre Déry, Gérald Barbeau, Bernard Noël, Éric Larose, Paul Poirier, Louis Roy
Journal: Circulation (2006)

Background— Systematic use of coronary stents and optimized platelet aggregation inhibition has greatly improved the short-term results of percutaneous coronary interventions. Transradial percutaneous coronary interventions have been associated with a low risk of bleeding complications. It is unknown whether moderate- and high-risk patients can be discharged safely the same day after uncomplicated transradial percutaneous coronary interventions. Methods and Results— We randomized 1005 patients after a bolus of abciximab and uncomplicated transradial percutaneous coronary stent implantation either to same-day home discharge and no infusion of abciximab (group 1, n=504) or to overnight hospitalization and a standard 12-hour infusion of abciximab (group 2, n=501). The primary composite end point of the study was the 30-day incidence of any of the following events: death, myocardial infarction, urgent revascularization, major bleeding, repeat hospitalization, access site complications, and severe thrombocytopenia. The noninferiority of same-day home discharge and bolus of abciximab only compared with overnight hospitalization and abciximab bolus and infusion was evaluated. Two thirds of patients presented with unstable angina and ≈20% presented with high-risk acute coronary syndrome prior to the procedure. The incidence of the primary end point was 20.4% in group 1 and 18.2% in group 2 ( P =0.017 for noninferiority) with a troponin T–based definition of myocardial infarction; the incidence of the primary end point was 11.1% in group 1 and 9.6% in group 2 ( P =0.0004 for noninferiority) with a creatinine kinase myocardial band–based definition of myocardial infarction. No death occurred. Rate of major bleeding in both groups was extremely low at 0.8% and 0.2%, respectively. From 504 patients randomized in group 1, 88% were discharged home the same day. Conclusion— Our data suggest that same-day home discharge after uncomplicated transradial coronary stenting and bolus only of abciximab is not clinically inferior, in a wide spectrum of patients, to the standard overnight hospitalization and a bolus followed by a 12-hour infusion. This novel approach offers a safe strategy for same-day home discharge after uncomplicated coronary intervention.
Molecular drift of the bride of sevenless (boss) gene in Drosophila.
Authors: F J Ayala, D L Hartl
Journal: Molecular Biology and Evolution (1993)

DNA sequences were determined for three to five alleles of the bride-of-sevenless (boss) gene in each of four species of Drosophila. The product of boss is a transmembrane receptor for a ligand coded by the sevenless gene that triggers differentiation of the R7 photoreceptor cell in the compound eye. Population parameters affecting the rate and pattern of molecular evolution of boss were estimated from the multinomial configurations of nucleotide polymorphisms of synonymous codons. The time of divergence between D. melanogaster and D. simulans was estimated as approximately 1 Myr, that between D. teissieri and D. yakuba as approximately 0.75 Myr, and that between the two pairs of sibling species as approximately 2 Myr. (The boss genes themselves have estimated divergence times approximately 50% greater than the species divergence times.) The effective size of the species was estimated as approximately 5 x 10(6), and the average mutation rate was estimated as 1-2 x 10(-9)/nucleotide/generation. The ratio of amino acid polymorphisms within species to fixed differences between species suggests that approximately 25% of all possible single-step amino acid replacements in the boss gene product may be selectively neutral or nearly neutral. The data also imply that random genetic drift has been responsible for virtually all of the observed differences in the portion of the boss gene analyzed among the four species.
T cell development in normal and thymopentin-treated nude mice.
Authors: G E Ranges, G Goldstein, E A Boyse, M P Schield
Journal: The Journal of Experimental Medicine (1982)

The extent and diversity of T cell differentiation in nude athymic mice are matters of dispute. In this study, we examined the splenic T cell population of pathogen-free and germ-free nu/nu mice, treated or not treated with the pentapeptide analogue of thymopoietin (TP-5), in terms of TL, Qa-1, and Lyt phenotypes. At all ages, 50-60% of nu/nu splenocytes, enriched for T lymphocytes by removal of sIg+ cells, expressed T markers, as compared with greater than 85% in normal mice. At 2 mo of age, all nu/nu splenic T cells expressed the surface phenotype TL+:Thy-1+:Ly-123. This is abnormal in two respects: first, because expression of TL is normally confined to thymocytes; and second, because there was no evidence of the usual diversification into the subsets Ly-1 and Ly-23. From 10 wk of age onwards, diversification into Ly subsets was evident in nu/nu spleen, although the usual predominance of Ly-1 over Ly-123 cells was not attained, and some TL+ cells persisted. Also, the ratio of Qa-1+ to Qa-1- cells rose progressively to as high as 4:1 at 4-6 mo, in contrast to the usual ratio of approximately 1:1, regardless of age. In the spleens of nu/nu mice treated with TP-5 from 5-8 weeks of age and tested 1 wk later, the proportion of T cells was raised, though not to normal levels, the number of TL+ cells was reduced, and there was diversification into Ly sets.
Increased CD36 Expression Signals Monocyte Activation Among Patients With Type 2 Diabetes
Authors: Yijuan Sun, Marina Scavini, Robert A. Orlando, Glen H. Murata, Karen S. Servilla, Antonios H. Tzamaloukas, Ronald Schrader, Edward J. Bedrick, Mark R. Burge, Nada A. Abumrad, Philip G. Zager
Journal: Diabetes Care (2010)

To explore the hypothesis that CD36, a scavenger receptor and fatty acid translocase, is upregulated in peripheral blood mononuclear cells (PBMCs) among patients with type 2 diabetes and is a biomarker of PBMC activation and inflammation.We used a cross-sectional observational design to study a multi-racial/ethnic population sample consisting of Caucasians, Hispanics, and Native Americans with type 2 diabetes (n = 33) and nondiabetic control subjects (n = 27). PBMC CD36 mRNA/protein and plasma high sensitivity (hs) C-reactive protein (hsCRP), hs-interleukin-6 (hsIL-6), and adiponectin were measured.Unadjusted PBMC CD36 mRNA and protein were 1.56- and 1.63-fold higher, respectively, among type 2 diabetic subjects versus control subjects. PBMC CD36 protein was directly associated with CD36 mRNA, plasma hsCRP, and hsIL-6 and inversely associated with plasma adiponectin in both groups.Increased CD36 expression is a biomarker of PBMC activation and inflammation and may become a useful tool in cardiovascular disease risk stratification.