tbuckley/cabot-search huggingface dataset:
Gap junctional communication and regulation of the glycogenic response to insulin by cell density and glucocorticoids in cultured fetal rat hepatocytes
Authors: Mashiat U. Siddiqui, Samia Benatmane, Jean-Luc Zachayus, Christiane Plas
Journal: Hepatology (1999)

Cell culture studies have revealed that metabolic functions of the adult hepatocyte are related to cell density. Development of the glycogenic response to insulin under glucocorticoid control was investigated in 15– and 18–day–old fetal rat hepatocytes plated at different cell densities. After culturing for 48 hours with glucocorticoids, the stimulatory effect of insulin on [ 14 C]glucose incorporation into glycogen after 3 hours progressed from weak response (less than 1.4–fold) in sparse cultures to a maximal response in dense ones (3.0– to 4.5–fold), depending on the fetal stage. The response was always no more than 2.0–fold in the absence of glucocorticoids, even with dense cultures. Such a dual regulation pattern was not found for the glycogenolytic effect of glucagon similarly expressed regardless of culture conditions. When cells were clustered in limited circular regions of the dish, the insulin response was higher than for sparse cultures for a similar number of cells per culture. Using the scrape–loading technique with Lucifer Yellow CH, a positive dye transfer was obtained in clustered cultures providing that they were grown in the presence of glucocorticoids; insulin as well as glucagon stimulated twofold intercellular communication. Connexin32 (Cx32) and connexin26 (Cx26) protein levels were assayed by Western immunoblotting and developed according to age and exposure to glucocorticoids. Thus, glucocorticoids through development of gap junctions enabled establishment of intercellular communication that could be stimulated by insulin and glucagon in cultured fetal hepatocytes. Gap junction functioning and the biologic effect of insulin correlated closely
Results With External Counterpulsation
Authors: PHILIP I. Hershberg
Journal: JAMA (1974)

<h3>To the Editor.—</h3> Soroff et al (229:1441, 1974) described results of external counterpulsation in 20 patients in Boston-area hospitals. The authors' conclusion that the 45% survival rate was a significant improvement over the usual 15% survival rate in cardiogenic shock needs comment. My personal experience in the field of counterpulsation started in 1964 as an electronics engineer. Together with Paul Freed, Dr. Adrian Kantrowitz and I built the first of a series of intra-aortic balloon pump (IABP) systems. After four years with Dr. Adrian Kantrowitz, I assisted Arthur Kantrowitz, PhD, in the development of the Avco IABP system. The Soroff article is one of a long line of similar reports suggesting that some new drug, chemical, or engineering device may be the answer to the treatment of the cardiogenic shock. The survival rate mentioned by Soroff et al was not 45% but only 35%, which means that 65% of the
Life-Threatening Malfunction of Implantable Cardiac Devices
Authors: Robert J Myerburg, David W Feigal, Bruce D Lindsay
Journal: New England Journal of Medicine (2006)

During the summer of 2005, in the wake of widespread criticism of its failure to communicate the potentially fatal malfunctions of its implantable defibrillators,1,2 Guidant Corporation created an independent panel, of which we were members. The purpose of the panel was to conduct an unbiased examination of these incidents, including the methods used to identify the malfunctions and evaluate products in the post-marketing phase and the policies regarding communication within the corporation and with physicians and patients. The panel was also asked to recommend corrective actions. Concurrently, the Heart Rhythm Society — which represents physicians who implant cardiac devices . . .
Aortic blood momentum – the more the better for the ejecting heart in vivo?
Authors: Motoaki Sugawara, Keisuke Uchida, Yukiyoshi Kondoh, Nobuhisa Magosaki, Kiyomi Niki, Christopher J.H Jones, Masaru Sugimachi, Kenji Sunagawa
Journal: Cardiovascular Research (1997)

The aim of the present study was to test two hypotheses: (1) the momentum of the blood flowing out of the left ventricle toward the aorta (inertia force) plays an important role in the initiation of decay and the maximum rate of decay (peak (-dP/dt)) of left ventricular pressure (P); (2) a normal heart itself generates the inertia force which enhances its function.The contribution of the inertia force to (-dP/dt) was theoretically given as rho c alpha, where rho is the blood density, c the pulse wave velocity, and alpha the deceleration rate of aortic blood flow. The correlations of peak (-dP/dt) with rho c alpha and with the time constant (tau) of the pressure decay during isovolumic relaxation, which was considered to represent myocardial relaxation characteristics, were compared in seven dogs. We developed a method of grading the strength of the inertia force, using the phase loop of left ventricular pressure (dP/dt vs. P relation). The method was applied to the records of 25 patients with ischemic heart disease, from which high fidelity left ventricular pressure recordings were available.The correlation of peak (-dP/dt) with rho c alpha was much higher than with tau (0.75 vs. -0.46). 16 of the 25 patients showed evidence of the inertia force. However, other patients showed no inertia force. The strength of the inertia force showed a significant (P < 0.05) correlation with left ventricular end-diastolic pressure (r = -0.46), cardiac index (r = 0.62), stroke volume index (r = 0.69), ejection fraction (r = 0.46), and peak (-dP/dt) (r = 0.56).The inertia force of late systolic aortic flow contributed to ventricular relaxation in the normal heart.
Cellular response to conditional expression of hepatitis C virus core protein in Huh7 cultured human hepatoma cells
Authors: Kui Li, Tarl Prow, Stanley M. Lemon, Michael R. Beard
Journal: Hepatology (2002)

Data suggesting that the hepatitis C virus (HCV) core protein influences normal cellular processes remain controversial. To determine the effects of core on cellular gene expression in hepatocytes, we developed a human hepatoma (Huh7)-derived cell line with tightly regulated core expression under the control of a tetracycline-regulated promoter. Cells expressing core did not have impaired proliferative abilities. Changes in gene expression profiles in response to core expression were determined using commercial oligonucleotide microarrays (Affymetrix GeneChip). Significant increases were observed in the abundance of mRNA-encoding members of the metallothionein (MT) family, as well as nicotinamide N -methyltransferase (NNMT) and glutathione peroxidase-like protein (GPLP). These changes did not result from removal of tetracycline from growth media, and were confirmed in reverse-transcription polymerase chain reaction (RT-PCR) assays. They suggest that core protein expression leads to intracellular oxidative stress, and that vital cellular functions are, in turn, protected by up-regulation of cellular antioxidant defense mechanisms. In conclusion, these findings can explain many potentially conflicting prior observations concerning the effects of core on cellular physiology, and are of relevance to the role of core protein in the pathogenesis of HCV-related fibrosis and hepatocellular carcinoma.
Role of Positive Feedback in the Atrioventricular Nodal Wenckebach Phenomenon
Authors: MATTHEW N. LEVY, PAUL J. MARTIN, HARRISON ZIESKE, DALE ADLER
Journal: Circulation Research (1974)

In the atrioventricular (AV) nodal Wenckebach phenomenon, there is a progressive increase in the P-R interval and a concomitant reduction in the R-P interval. Two series of experiments were conducted on anesthetized dogs to ascertain whether the changes in the P-R interval depended on the associated changes in the R-P interval. In one series of experiments, the atrium was paced at various basic cycle lengths, and a single test cycle was interposed about every 100 beats. When the test cycle was very short, the increase in the P-R interval sometimes exceeded the associated reduction in the R-P interval. During the subsequent basic cycle, although the P-P interval was much greater than it was during the test cycle, there was a further reduction in the R-P interval. When this change in the R-P interval was appreciable, AV conduction failed despite the increase in cycle length. In the second series of experiments, the AV nodal Wenckebach phenomenon was induced by rapid atrial pacing. When the stimulation mode was suddenly altered to maintain a constant R-P interval, the Wenckebach rhythm immediately ceased, although the mean heart rate had not changed significantly. Therefore, it appears that above a critical heart rate a positive feedback loop is established in which an increase in the P-R interval evokes a corresponding decrease in the R-P interval. In turn, the curtailed R-P interval that reflects a less complete recovery of AV nodal excitability elicits a still greater increase in the P-R interval. This cycle continues until an impulse is ultimately blocked. Clamping the R-P interval opens the feedback loop and terminates the arrhythmia.
Judge: No Age Restriction for Emergency Contraceptive
Authors: Bridget M. Kuehn
Journal: JAMA (2013)

A federal judge has ordered the US Food and Drug Administration (FDA) to act within 30 days to make emergency contraceptives available over the counter to adolescents without a prescription. The ruling applies to levonorgestrel-based products that are currently available without prescription to women aged 17 years or older. The drugs help prevent pregnancy if taken within 3 days of unprotected intercourse.
Time-Related Normalization of Maximal Coronary Flow in Isolated Perfused Hearts of Rats With Myocardial Infarction
Authors: H.J. Marjorie G. Nelissen-Vrancken, Jacques J.M. Debets, Luc H.E.H. Snoeckx, Mat J.A.P. Daemen, Jos F.M. Smits
Journal: Circulation (1996)

Background In the present study, we investigated the time dependency and regional differences of the vascular adaptation of the myocardium after myocardial infarction (MI) in rats. Methods and Results MI was induced by total occlusion of the left anterior descending coronary artery. Time-dependent adaptation of the coronary vasculature was determined by histological staining of endothelial cells and measurement of basal and maximal coronary flow at days 0, 4, 7, 21, 35, and 90 after surgery in isolated retrogradely perfused hearts of sham-operated and infarcted rats. Cardiac function was determined during anterograde perfusion. In a separate group of experiments, regional myocardial flow was measured with radiolabeled microspheres in sham-operated and infarcted hearts to determine local differences in adaptation. Basal coronary flow was completely normalized within 7 days, whereas maximal coronary flow was not normalized until 35 days after MI. Normal growth, as observed in sham-operated hearts, resulted in a parallel increase in coronary flow and tissue mass from day 7 to 35 after surgery. In contrast, the increase in coronary flow was lower than the hypertrophic response in the right ventricles and septa of infarcted hearts, whereas a parallel increase in tissue mass and coronary flow was observed in the left ventricles of these hearts. These functional data were supported by structural data that showed the presence of numerous and dilated vessels, especially in the border zone of the infarcted and noninfarcted tissue. Conclusions These observations demonstrate that vessel growth, predominantly in the region adjacent to the infarcted zone, results in complete normalization of coronary vasodilatory capacity within 35 days after MI.
Immunoglobulin recombinase gene activity is modulated reciprocally by interleukin 7 and CD19 in B cell progenitors.
Authors: L G Billips, C A Nuñez, F E Bertrand, A K Stankovic, G L Gartland, P D Burrows, M D Cooper
Journal: The Journal of Experimental Medicine (1995)

Bone marrow stromal cells promote B cell development involving recombinase gene-directed rearrangement of the immunoglobulin genes. We observed that the stromal cell-derived cytokine interleukin 7 (IL-7) enhances the expression of CD19 molecules on progenitor B-lineage cells in human bone marrow samples and downregulates the expression of terminal deoxynucleotidyl transferase (TdT) and the recombinase-activating genes RAG-1 and RAG-2. Initiation of the TdT downregulation on the first day of treatment, CD19 upregulation during the second day, and RAG-1 and RAG-2 downmodulation during the third day implied a cascade of IL-7 effects. While CD19 ligation by divalent antibodies had no direct effect on TdT or RAG gene expression, CD19 cross-linkage complete blocked the IL-7 downregulation of RAG expression without affecting the earlier TdT response. These results suggest that signals generated through CD19 and the IL-7 receptor could modulate immunoglobulin gene rearrangement and repertoire diversification during the early stages of B cell differentiation.
Racial Inequities in Kidney Transplantation: The UNOS Perspective
Authors: Douglas J. Norman
Journal: JAMA (1994)

<h3>To the Editor.</h3> —Dr Gaston and colleagues<sup>1</sup>describe some of the factors that contribute to racial disparity in end-stage renal disease and transplantation in the United States. They set forth the premise that HLA matching, as used in the current kidney allocation system, is responsible for perceived racial inequities in kidney transplantation. However, the authors fail to clearly demonstrate a causal relationship between the role of HLA matching in the current renal allocation system and unequal renal transplant waiting times observed across racial groups. Data analyzed for a United Network for Organ Sharing (UNOS) research report, being prepared for publication in 1994, indicate that the distribution of renal offers according to patient race is much more equitable than one might expect after examining waiting time differences across racial groups. Data to be reported show that every time a kidney becomes available, many factors come into play after patients on
PARP alleles within the linked chromosomal region are associated with systemic lupus erythematosus
Authors: Betty P. Tsao, Rita M. Cantor, Jennifer M. Grossman, Nan Shen, Nickolay T. Teophilov, Daniel J. Wallace, Frank C. Arnett, Klaus Hartung, Rose Goldstein, Kenneth C. Kalunian, Bevra H. Hahn, Jerome I. Rotter
Journal: Journal of Clinical Investigation (1999)

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by various autoantibodies that recognize autoantigens displayed on the surface of cells undergoing apoptosis. The genetic contribution to SLE susceptibility has been widely recognized. We previously reported evidence for linkage to SLE of the human chromosome 1q41–q42 region and have now narrowed it from 15 to 5 cM in an extended sample using multipoint linkage analysis. Candidate genes within this region include (a) PARP, poly(ADP-ribose) polymerase, encoding a zinc-finger DNA-binding protein that is involved in DNA repair and apoptosis; (b) TGFB2, encoding a transforming growth factor that regulates cellular interactions and responses; and (c) HLX1, encoding a homeobox protein that may regulate T-cell development. Using a multiallelic, transmission-disequilibrium test (TDT), we found overall skewing of transmission of PARP alleles to affected offspring in 124 families (P = 0.00008), preferential transmission of a PARP allele to affected offspring (P = 0.0003), and lack of transmission to unaffected offspring (P = 0.004). Similar TDT analyses of TGFB2 and HLX1 polymorphisms yielded no evidence for association with SLE. These results suggest that PARP may be (or is close to) the susceptibility gene within the chromosome 1q41–q42 region linked to SLE.
A Longitudinal Study of Low-Level Lead Exposure and Impairment of Renal Function
Authors: Rokho Kim
Journal: JAMA (1996)

To determine whether low-level lead exposure is associated with impaired renal function.Retrospective cohort study.Subjects were 459 men randomly selected from the participants of the Normative Aging Study who were originally recruited from healthy veterans in the greater Boston area in 1961 and were periodically examined at the Department of Veterans Affairs Outpatient Clinic every 3 to 5 years. We reconstructed blood lead concentrations for the period between 1979 and 1994 using samples of either archived red blood cells or fresh whole blood.Serum creatinine concentration.After adjustment for age, body mass index, smoking, alcohol consumption, educational level, and hypertension, blood lead concentration was positively and significantly associated with concurrent concentration of serum creatinine (P=.005). A 10-fold increase in blood lead level predicted an increase of 7 micromol/L (0.08 micrograms/dL) in serum creatinine concentration, which is roughly equivalent to the increase predicted by 20 years of aging. The association was also significant among subjects whose blood lead concentrations had never exceeded 0.48 micromol/L (10 micrograms/L) throughout the study period. The age-related increase in serum creatinine level was earlier and faster in the group with the highest-quartile levels of long-term lead exposure than in the group with the lowest-quartile levels.Low-level exposure to lead may impair renal function in middle-aged and older men. Longitudinal data suggest an acceleration of age-related impairment of renal function in association with long-term low-level lead exposure.
Abstract 2467: Development of new N-Arylbenzamides as STAT3 dimerization inhibitors.
Authors: Nicholas J. Lawrence, Roberta Pireddu, Yiyu Ge, Murali K. Urlam, Xiaolei Zhang, Ying Sun, Harshani R. Lawrence, Wayne C. Guida, Said Sebti
Journal: Cancer Research (2013)

Abstract The association of aberrant STAT3 activation with many types of human malignancies and solid tumors makes STAT3 an attractive molecular target for the development of novel cancer therapeutics. STAT3 dimerization via two reciprocal phosphotyrosine (pTyr)-Src-homology 2 (SH2) interaction is required for its binding to specific DNA-response elements in the promoters of target genes. This dimerization process offers a potentially selective way to directly target STAT3. Nevertheless the design of small molecules capable of disrupting protein-protein interactions remains a significant challenge to medicinal chemistry. We describe the development of a new class of small molecule capable of disrupting the STAT3:STAT3 protein-protein interaction. We identified the STAT3 inhibitor S3I-201 (NSC-74859) from the NCI chemical collection by using structure-based virtual screening with a model based on the X-ray crystal structure of the STAT3β homodimer. We developed a series of phosphonic and salicylic acids based on the structure of S3I-201 incorporating an N-arylbenzamide scaffold. The series of phosphonic and salicylic acids with a shorter amide linker lacking the O-tosyl group has improved STAT3 inhibitory activity [as measured by a competitive, fluorescence-polarization (FP)-based assay]. The equivalent in vitro potencies observed by the replacement of phosphonic acid moiety of with 5-amino-2-hydroxybenzoic acid group validates 5-amino-2-hydroxybenzoic acid as a phosphotyrosine mimic in this series. The binding mode of selected compounds, as predicted by molecular modeling, will be discussed. Our docking studies indicated that the phosphonic and salicylic acid groups interact in the pTyr-705 binding site in a broadly similar manner, while the other substituents occupy the STAT3 pY+1 and pY-X hydrophobic pockets. One of the most potent compounds in vitro (in the FP assay) inhibits STAT3 dimerization in intact cells and suppresses malignant transformation in human cancer cells that depend on STAT3. The in vitro and cell based potency of the N-arylbenzamides warrants further development of this scaffold as STAT3 inhibitors. Citation Format: Nicholas J. Lawrence, Roberta Pireddu, Yiyu Ge, Murali K. Urlam, Xiaolei Zhang, Ying Sun, Harshani R. Lawrence, Wayne C. Guida, Said Sebti. Development of new N-Arylbenzamides as STAT3 dimerization inhibitors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2467. doi:10.1158/1538-7445.AM2013-2467
Low-molecular-weight heparin versus low-dose aspirin in women with one fetal loss and a constitutional thrombophilic disorder
Authors: Jean-Christophe Gris, Eric Mercier, Isabelle Quéré, Géraldine Lavigne-Lissalde, Eva Cochery-Nouvellon, Médéric Hoffet, Sylvie Ripart-Neveu, Marie-Laure Tailland, Michel Dauzat, Pierre Marès
Journal: Blood (2004)
Roles of Heat Shock Factor 1 in Neuronal Response to Fetal Environmental Risks and Its Relevance to Brain Disorders
Authors: Kazue Hashimoto-Torii, Masaaki Torii, Mitsuaki Fujimoto, Akira Nakai, Rachid El Fatimy, Valerie Mezger, Min J. Ju, Seiji Ishii, Shih-hui Chao, Kristen J. Brennand, Fred H. Gage, Pasko Rakic
Journal: Neuron (2014)
Prevention and treatment of surgical site infection: summary of NICE guidance
Authors: D. Leaper, S. Burman-Roy, A. Palanca, K. Cullen, D. Worster, E. Gautam-Aitken, M. Whittle
Journal: BMJ (2008)

The consequences of infection at the site of surgery can be devastating to the patient and costly to manage, often requiring readmission to hospital. Surgical site infections account for 14% of all healthcare acquired infections.1 This article summarises the most recent guidance from the National Institute for Health and Clinical Excellence (NICE) for the prevention and management of surgical site infection.2 NICE recommendations are based on systematic reviews of best available evidence. When minimal evidence is available, recommendations are based on the guideline development group's opinion of what constitutes good practice. Evidence levels for the recommendations are given in italic in square brackets. ### Information for patients and carers Provide patients and carers with clear and consistent, easily understood information and advice throughout all stages of their care. Information should include: [ All these recommendations are based on a high quality randomised controlled trial and on the opinion of the Guideline Development Group ] ### Preoperative phase #### Showering #### Hair removal
586 Tamoxifen (TMX)-induced hepatotoxicity in breast cancer (BC) patients with pre-existing liver steatosis (LS). The role of glucose intolerance
Authors: I.S. Elefsiniotis, K.D. Pantazis, A. Ilias, L. Pallis, A. Mariolis, I. Glynou, H. Kada, A. Moulakakis
Journal: Journal of Hepatology (2004)
Study subject to unmeasured confounders and biases
Authors: A. Szarewski, D. Mansour
Journal: BMJ (2011)

The papers on venous thromboembolism in oral contraceptive users have similar faults to earlier database studies.1 2 These include lack of validation of venous thromboembolism (VTE) cases and lack of information on, or control of, important potential confounders such as duration of use, especially short duration use; family history; body mass index (BMI); and smoking.3 Jick and Hernandez’s …
The possible role of ChemR23/Chemerin axis in the recruitment of dendritic cells in lupus nephritis
Authors: Giuseppe De Palma, Giuseppe Castellano, Annalisa Del Prete, Silvano Sozzani, Nicoletta Fiore, Antonia Loverre, Marc Parmentier, Loreto Gesualdo, Giuseppe Grandaliano, Francesco P. Schena
Journal: Kidney International (2011)
CHEMICAL STUDIES ON INTESTINAL INFANTILISM
Authors: Francis H. McCrudden
Journal: The Journal of Experimental Medicine (1912)

In my three cases of intestinal infantilism, the kreatinin excretion was more irregular than normally, and the kreatinin coefficient was low. Kreatin was found in the urine on a kreatin-free diet. The sum of kreatinin and kreatin was also irregular. The endogenous uric acid was irregular from day to day. The kreatin excretion is apparently lower on a high fat diet than on a high carbohydrate diet.