tbuckley/cabot-search huggingface dataset:
Triggered propagated contractions in human atrial trabeculae
Authors: M. C G Daniels, T. Kieser, H. E D J ter Keurs
Journal: Cardiovascular Research (1993)

Objective: Mechanical stretch and rapid release of locally damaged regions of rat cardiac trabeculae due to contraction of undamaged cells during the regular twitch have been shown to trigger local aftercontractions in the damaged region. These aftercontractions appear to propagate along the length of the trabeculae and to precede triggered arrhythmias. The aim of this study was to determine whether triggered propagated contractions can also be elicited in human cardiac tissue. Methods: Trabeculae were dissected from a biopsy of the right atrial appendage which was obtained during cardiac surgery. They were mounted horizontally, supervised with a modified Krebs-Henseleit solution, and monitored with a video system. Force was measured with a silicon strain gauge; sarcomere length was measured with laser diffraction techniques. Triggered contractions were elicited in 10 trabeculae following trains of 15 stimuli at a rate of 2 Hz, separated by 15 s rest intervals, at 21°C and a [Ca2+]o above 5.0 mM. Results: Both video analysis and sarcomere length recordings showed that the contractions started at one end of the trabeculae and travelled from there as a localised contraction along the muscle. Increasing [Ca2+]o or the number of conditioning stimuli increased force of the stimulated twitches up to a maximum; further increase of [Ca2+]o or the number of stimuli was accompanied by a decrease of force. Force of the triggered propagated contractions increased monotonically with increasing [Ca2+]o and number of stimuli, while the interval between last stimulus and the peak of the force transient (or latency) decreased progressively, and propagation velocity increased monotonically. Propagation velocity was calculated from the interval between peak sarcomere shortening at two sites and the distance between these sites, as well as from the ratio between the length of the muscle and the duration of the force transient in the remainder of the trabeculae. With increasing temperature at constant [Ca2+]o twitch force increased while latency, force, and duration of the force transient decreased. At 37°C, localised contractions travelling along the muscle could still be induced at sufficiently increased [Ca2+]o. For all interventions, propagation velocity varied from 0.8 to 3.9 mm·s−1. Conclusions: Contractions can be elicited in human atrial cardiac trabeculae. These contractions have the same basic characteristics as the triggered propagated contractions that have been described previously in rat ventricular trabeculae. Cardiovascular Research 1993;27:1831-1835
Carcinogenicity of food mutagens.
Authors: T Sugimura, M Nagao, K Wakabayashi
Journal: Environmental Health Perspectives (1996)

Cancer cells are produced by the accumulation of genetic alterations in somatic cells. Those genetic alterations are produced by xenobiotics, which enter the human body from the environment, and by autobiotics, which are produced in the human body. Food contains many different types of xenobiotic mutagens/carcinogens and tumor promoters. Food can influence the formation of autobiotic mutagens/carcinogens and give rise to tumor-promoting conditions. In spite of this, it can also contain many antimutagenic, anticarcinogenic, and antitumor-promoting substances. Carcinogenic risk and anticarcinogenic efficacy are hard to express quantitatively; however, holistic approaches that are designed to improve lifestyle are realistic for cancer prevention.
LYSOSOMES IN RAT THORACIC DUCT LYMPHOCYTES
Authors: William E. Bowers
Journal: The Journal of Experimental Medicine (1972)

10 acid hydrolases known to be lysosomal in other tissues were detected in rat thoracic duct lymphocytes (TDL). Except for cathepsin D, all these enzymes occurred in lower levels in TDL than in rat spleen. Fractionation by means of differential centrifugation revealed two types of distribution patterns. Most of the total cathepsin D activity appeared in a high-speed supernatant (S), whereas the other acid hydrolases associated mainly with a high-speed pellet (P). Further studies by isopycnic centrifugation in a sucrose density gradient showed that all the enzymes, including a small portion of cathepsin D, sedimented around a modal density of 1.18. In contrast, most cathepsin D activity was recovered in a soluble, unsedimentable form. These results suggest the presence of two populations of lysosomes. Because the possibility could be excluded that other cell types contaminated the lymphocyte preparations, it is concluded that both lysosomal populations arise from TDL.
Islet-Cell Tumor of the Pancreas with Hyperinsulinism
Authors: Alexander Marble, Leland S. McKittrick
Journal: New England Journal of Medicine (1946)

ALTHOUGH in recent years many publications regarding patients with pancreatic islet-cell tumors have appeared, the condition is sufficiently infrequent to make additional reports desirable.1 Since 1938 we have observed 6 patients in whom the diagnosis was verified at operation performed by one of us (L. S. McK.). Our experience with these patients forms the basis for the present paper. A report is particularly worth while at the present time because it provides a four-year to seven-year postoperative follow-up study of the patients concerned. In 5 of the 6 cases removal of a single adenoma at operation resulted in relief of . . .
Active CREB1 Promotes a Malignant TGFβ2 Autocrine Loop in Glioblastoma
Authors: Laura Rodón, Alba Gonzàlez-Juncà, María del Mar Inda, Ada Sala-Hojman, Elena Martínez-Sáez, Joan Seoane
Journal: Cancer Discovery (2014)

In advanced cancer, including glioblastoma, the TGFβ pathway acts as an oncogenic factor. Some tumors exhibit aberrantly high TGFβ activity, and the mechanisms underlying this phenomenon are not well understood. We have observed that TGFβ can induce TGFβ2, generating an autocrine loop leading to aberrantly high levels of TGFβ2. We identified cAMP-responsive element-binding protein 1 (CREB1) as the critical mediator of the induction of TGFβ2 by TGFβ. CREB1 binds to the TGFB2 gene promoter in cooperation with SMAD3 and is required for TGFβ to activate transcription. Moreover, the PI3K-AKT and RSK pathways regulate the TGFβ2 autocrine loop through CREB1. The levels of CREB1 and active phosphorylated CREB1 correlate with TGFβ2 in glioblastoma. In addition, using patient-derived in vivo models of glioblastoma, we found that CREB1 levels determine the expression of TGFβ2. Our results show that CREB1 can be considered a biomarker to stratify patients for anti-TGFβ treatments and a therapeutic target in glioblastoma.TGFβ is considered a promising therapeutic target, and several clinical trials using TGFβ inhibitors are generating encouraging results. Here, we discerned the molecular mechanisms responsible for the aberrantly high levels of TGFβ2 found in certain tumors, and we propose biomarkers to predict the clinical response to anti-TGFβ therapies.
Calcium-dependent enhancement of myocardial diastolic tone and energy utilization dissociates systolic work and oxygen consumption during low sodium perfusion.
Authors: D G Renlund, E G Lakatta, E D Mellits, G Gerstenblith
Journal: Circulation Research (1985)

The relationships and correlations among functional, metabolic, and ionic consequences of low sodium perfusion were studied in isovolumic, retrograde-aortic perfused working rat hearts by 31P nuclear magnetic resonance, oxygen consumption, and atomic absorption spectrometry. Reduction of perfusate sodium from 144 to 74, 51, 39, and 25 mM in four separate groups of hearts via lithium substitution for 15 minutes decreased cell sodium to mean values of 62, 51, 43, and 36 mumol/g dry weight, respectively (P less than 0.001 vs. control of 107). There was a transient rise and then a fall in developed pressure and a decline in phosphocreatine and adenosine triphosphate, all of which were graded and correlated with perfusate sodium (P less than 0.01 for all parameters vs. perfusate sodium). This was accompanied by a 2- to 7-fold elevation of diastolic pressure while oxygen consumption remained near control levels. All parameters except adenosine triphosphate returned toward baseline values when normal perfusate sodium was reintroduced. Although cell calcium as measured by atomic absorption spectrometry did not differ among the groups, the functional and metabolic changes did not occur if the sodium steps were performed in reduced perfusate calcium (0.08 mM). In hearts in which systolic function was obliterated by verapamil, exposure to zero sodium caused a 4-fold increase in oxygen consumption, an increase in diastolic pressure, and a reduction of high energy phosphates. In the presence of ryanodine, a specific inhibitor of sarcoplasmic reticulum calcium release, the metabolic changes did not occur, and the excess oxygen consumption in zero sodium was substantially reduced. Thus, the effect of lowered perfusate sodium in beating hearts, i.e., to dissociate oxygen consumption and systolic function, and to increase diastolic pressure and its effect in arrested hearts to increase oxygen consumption, are calcium dependent, energy consuming, and modulated by sarcoplasmic reticulum calcium cycling.
String quartets by Bedrich Smetana
Authors: D. O'Neill
Journal: BMJ (2012)

<b>Background:</b> Despite the advances in immunosuppression, the acute lung rejection remains a significant risk in lung transplantation. <b>Aim:</b> In the present study, we aimed to investigate the gene expression profile of aquaporins (AQP) in lung transplant recipients with acute rejection as compared to healthy controls. <b>Materials and Methods:</b> Gene expression data of AQP1-6, 8, 9 were extracted and analyzed from the PubMed GEO database (https://www.ncbi.nlm.nih.gov/gds). A total of 34 samples of bronchoalveolar lavage cells were analyzed. Rejection status was determined from biopsies. The gene expression data were log-transformed and the standard deviation was normalized to one per array. Genes were considered differentially expressed when their fold change was significantly higher or lower between groups (p&lt;0.05). <b>Results:</b> We found that the AQP2 gene was significantly over-expressed in patients with acute rejection compared to control group (p=0.0426). In contrast, the AQP3 gene was significantly under-expressed in patients with acute rejection compared to the control group (p=0.0493). No significant difference of gene expression level was found regarding AQP1, 4, 5, 6, 8, 9. <b>Conclusions:</b> Our results indicate that AQP2 was over-expressed and AQP3 was under-expressed in lung transplant recipients with acute lung rejection. These results set the basis for the further assessment of the pathophysiological role of AQP2 and AQP3 in acute rejection after lung transplantation, along with their potential utility as biomarkers.
Increased serum nitrite and nitrate levels in patients with cirrhosis: Relationship to endotoxemia
Authors: Carlos Guarner, German Soriano, Albert Tomas, Oriol Bulbena, Maria Teresa Novella, Joaquin Balanzo, Francisco Vilardell, Marisabel Mourelle, Salvador Moncada
Journal: Hepatology (1993)

Nitric oxide derived from vascular endothelium is a potent vasodilator that plays a key role in the homeostasis of blood pressure. Because cirrhotic patients tend to have low arterial pressure, we measured in 51 patients and 10 control subjects serum nitrite and nitrate levels as an index of in vivo nitric oxide generation. We also measured plasma endotoxin, a substance frequently increased in cirrhotic patients and known to induce nitric oxide synthesis. Cirrhotic patients showed significant increases in serum nitrite/nitrate and plasma endotoxin compared with controls. Values were particularly increased in patients with decompensated cirrhosis, as manifested by ascites with or without functional kidney failure. High serum nitrite/nitrate levels were associated with high plasma renin activity, high aldosterone and antidiuretic hormone levels and low urinary excretion of sodium. In addition, serum nitrite/nitrate levels significantly correlated with endotoxemia. Oral administration of colistin to 15 cirrhotic patients reduced significantly plasma endotoxin levels (p < 0.01) and serum nitrite/nitrate levels (p < 0.05). Because endotoxin enhances the expression of inducible nitric oxide synthase, our results suggest that circulating endotoxin in cirrhosis is responsible for excessive synthesis and release of nitric oxide by the vasculature. These findings might explain the hemodynamic dysfunction seen in cirrhotic patients.
Risk of Post-Transfusion Viral Hepatitis
Authors: George F. Grady, Thomas C. Chalmers
Journal: New England Journal of Medicine (1964)

HEPATITIS is noted in a small percentage of patients who have been transfused within the previous six months. Determination of the exact incidence is hampered by the difficulty in following a large number of scattered blood recipients throughout a long potential incubation period. When no other likely explanation for the disease can be found it is often suspected that it has been caused by an unidentified virus transmitted in the donor's blood. This suspicion can be confirmed only rarely, when multiple cases can be traced to the same blood donor.In spite of these difficulties many estimates of the incidence . . .
Three Measures of Forest Fire Smoke Exposure and Their Associations with Respiratory and Cardiovascular Health Outcomes in a Population-Based Cohort
Authors: Sarah B. Henderson, Michael Brauer, Ying C. MacNab, Susan M. Kennedy
Journal: Environmental Health Perspectives (2011)

Background: During the summer of 2003 numerous fires burned in British Columbia, Canada.Objectives: We examined the associations between respiratory and cardiovascular physician visits and hospital admissions, and three measures of smoke exposure over a 92-day study period (1 July to 30 September 2003).Methods: A population-based cohort of 281,711 residents was identified from administrative data. Spatially specific daily exposure estimates were assigned to each subject based on total measurements of particulate matter (PM) ≤ 10 μm in aerodynamic diameter (PM10) from six regulatory tapered element oscillating microbalance (TEOM) air quality monitors, smoke-related PM10 from a CALPUFF dispersion model run for the study, and a SMOKE exposure metric for plumes visible in satellite images. Logistic regression with repeated measures was used to estimate associations with each outcome.Results: The mean (± SD) exposure based on TEOM-measured PM10 was 29 ± 31 μg/m3, with an interquartile range of 14–31 μg/m3. Correlations between the TEOM, smoke, and CALPUFF metrics were moderate (0.37–0.76). Odds ratios (ORs) for a 30-μg/m3 increase in TEOM-based PM10 were 1.05 [95% confidence interval (CI), 1.03–1.06] for all respiratory physician visits, 1.16 (95% CI, 1.09–1.23) for asthma-specific visits, and 1.15 (95% CI, 1.00–1.29) for respiratory hospital admissions. Associations with cardiovascular outcomes were largely null.Conclusions: Overall we found that increases in TEOM-measured PM10 were associated with increased odds of respiratory physician visits and hospital admissions, but not with cardiovascular health outcomes. Results indicating effects of fire smoke on respiratory outcomes are consistent with previous studies, as are the null results for cardiovascular outcomes. Some agreement between TEOM and the other metrics suggests that exposure assessment tools that are independent of air quality monitoring may be useful with further refinement.
Abstract 2605: CE-TOFMS metabolome analysis for pharmacological responses to CPT-11 in colorectal cancer cells with different chemosensitivities
Authors: Akito Nishimuta, Tetsuya Suzuki, Eri Arita, Masahiro Sugimoto, Tomoyoshi Soga, Yusuke Tanigawara
Journal: Cancer Research (2010)

Abstract Purpose: The topoisomerase I inhibitor irinotecan (CPT-11) is widely used for the treatment of metastatic colorectal cancer. However, mechanism to determine pharmacological response to CPT-11 is still unclear. We reported the application of a novel metabolomic analysis using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS) on the study of metabolic responses to anticancer agents (AACR #2563 and #4785, 2008 and #3764, 2009). The purpose of this study is to compare the metabolomic responses to SN-38, the active metabolite of CPT-11, between high-sensitive and low-sensitive colorectal cancer cells, for finding new biomarkers that can predict CPT-11 response. Experimental Procedures: To elucidate metabolomic responses to SN-38, human colorectal carcinoma, HCT116 and HT29 cells were exposed to 50 nM SN-38. At time 0, 3, 8, and 24 h after SN-38 exposure, all intracellular metabolites were extracted by liquid-liquid extraction and simultaneously analyzed by CE-TOFMS. To find out low molecular weight compounds related to the sensitivity to SN-38, the metabolomic profiles were compared across the 8 colorectal cancer cell lines and sensitivity to SN-38 was investigated. Results: The HCT116 cells were more sensitive to SN-38 than HT29. The intracellular metabolites of key pathways for cellular activity were quantitatively analyzed by CE-TOFMS, which included glycolysis, tricarboxylic acid (TCA) cycles, urea cycles, amino acid metabolism and pyrimidine metabolism. The intracellular levels of endogenous deoxyribonucleotides (dTTP and dCTP) increased after SN-38 exposure in both cells. In contrast, ribonucleotides such as CTP and UTP of RNA synthesis pathway were not affected by SN-38 exposure in either cell. These results imply the change in deoxyribonucleotide pool due to the disruption of DNA synthesis by topoisomerase I inhibition, the main anti-cancer mechanism of SN-38. It was also found that lactate and glycerol-3-phosphate were accumulated to a greater extent in HCT116 than in HT29. Furthermore, correlation analysis using 8 colorectal cancer cell lines revealed that the intracellular level of γ-aminobutyric acid (GABA) strongly correlated with cellular sensitivity to SN-38. Conclusions: The present CE-TOFMS metabolome analysis created a new finding on metabolomic mechanisms for response to SN-38 by colorectal cancer cells with different chemosensitivities. GABA was found to be a potential low molecular weight biomarker that may be used for predicting CPT-11 response. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2605.
The Loss and Progressive Recovery of Voiding after Spinal Cord Interruption in Rats is Associated with Simultaneous Changes in Autonomous Contractile Bladder Activity
Authors: Thomas Gevaert, Grzegorz Owsianik, Graham Hutchings, Liesbeth Van Leuven, Wouter Everaerts, Bernd Nilius, Dirk De Ridder
Journal: European Urology (2008)
Relationship of HLA protein display to activation of 2-5A synthetase in HBe antigen or anti-HBe positive chronic HBV infection.
Authors: T Ikeda, M Pignatelli, A M Lever, H C Thomas
Journal: Gut (1986)

In this study we have examined the density of HLA class I protein display on the hepatocytes of patients with HBe antigen (HBeAg) or anti-HBe (HBeAb) positive chronic hepatitis B virus (HBV) infection and related this to the level of interferon activation of these cells determined by measuring hepatic oligo 2-5A synthetase activity. In HBeAg positive patients the density of HLA class I (HLA-I) protein was not significantly increased above that found in uninfected liver, but levels of 2-5A synthetase were twice normal. In anti-HBe positive patients, HLA-I density was markedly increased in the presence of normal 2-5A synthetase activity. These data are consistent with type I (alpha or beta) interferon activation of the hepatocytes in HBeAg positive patients and type II (gamma) interferon activity in anti-HBe positive subjects.
Treatment of Bowen's disease and erythroplasia of Queyrat
Authors: J.P. Arlette
Journal: British Journal of Dermatology (2003)

Bowen's disease of the skin may have differing clinical presentations depending on the skin surface on which it presents, but has the same histologic features of squamous cell carcinoma in situ wherever it occurs. The etiologic factors include ultraviolet light and human papillomavirus infection. The choice of therapy requires a consideration for retention of form, function and cosmosis while offering a high cure rate. The immunodualtory agent imiquimod has been shown to be an effective treatment on a variety of skin surfaces.
High Incidence of Glucose Intolerance in Asian-Indian Subjects With Acute Coronary Syndrome
Authors: Ambady Ramachandran, Snehalatha Chamukuttan, Sathyamurthy Immaneni, Ravi Marimuthu Shanmugam, Nalini Vishnu, Vijay Viswanathan, Tuomilehto Jaakko
Journal: Diabetes Care (2005)

The risk of diabetes and coronary heart disease is high in Asian Indians. In this study, we aim to assess 1) the prevalence of hyperglycemia in incident acute coronary syndrome (ACS), 2) the effect of glycemia on the outcome, and 3) the association of plasma levels of insulin and proinsulin with ACS.A total of 146 nondiabetic subjects (121 men, 25 women) with ACS admitted to two hospitals in 1 year were enrolled. Random blood glucose at admission and a standard oral glucose tolerance test within 3 days were done. Glucose tolerance was categorized as normal glucose tolerance, impaired glucose tolerance (IGT) or impaired fasting glucose, and diabetes. Diabetes was arbitrarily classified further as undiagnosed (HbA1c [A1C] >6.0%) or possibly stress diabetes (A1C <6.0%). Subjects not on antidiabetic treatment were reassessed with a glucose tolerance test between 1 and 2 months. Fasting plasma specific insulin, proinsulin, their molar ratios, and insulin resistance (homeostasis model assessment) were estimated at baseline.Mean age of the cohort was 55 +/- 10.6 (SD) years. At baseline, 24 (16.4%) had normal glucose tolerance, 67 (45.9%) had IGT or impaired fasting glucose, and 55 (37%) had diabetes (35 [24%] were undiagnosed and 20 [13.7%] had stress diabetes). At follow-up, 53 of 92 responders (57.6%) continued to have IGT or diabetes. Mean baseline plasma insulin, proinsulin and its ratios, and insulin resistance were higher than normal in all subgroups.Nondiabetic Asian Indians showed a high prevalence of hyperglycemia following ACS. ACS was associated with insulin resistance and increased levels of specific insulin, proinsulin, and high proinsulin-to-insulin ratios.