tbuckley/cabot-search huggingface dataset:
Insulin Resistance and Risk of Chronic Kidney Disease in Nondiabetic US Adults
Authors: Jing Chen, Paul Muntner, L Lee Hamm, Vivian Fonseca, Vecihi Batuman, Paul K Whelton, Jiang He
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. This study examined the relationship of fasting serum glucose, insulin, C-peptide, glycosylated hemoglobin A (HbA1c), and Homeostasis Model Assessment (HOMA)-insulin resistance to risk of chronic kidney disease (CKD) among 6453 persons without diabetes (fasting glucose &lt;126 mg/dl and not taking diabetes medication) who participated in the Third National Health and Nutrition Examination Survey and were aged 20 yr or older. CKD was defined as an estimated GFR &lt;60 ml/min per 1.73 m<sup>2</sup>. The prevalence of CKD was significantly and progressively higher with increasing levels of serum insulin, C-peptide, HbA1c, and HOMA-insulin resistance. After adjustment for potential confounding variables, the odds ratio of CKD for the highest compared with the lowest quartile was 4.03 (95% confidence interval [CI], 1.81 to 8.95; <i>P</i> = 0.001), 11.4 (95% CI, 4.07 to 32.1; <i>P</i> &lt; 0.001), 2.67 (95% CI, 1.31 to 5.46; <i>P</i> = 0.002), and 2.65 (95% CI, 1.25 to 5.62; <i>P</i> = 0.008) for serum insulin, C-peptide, HbA1c levels, and HOMA-insulin resistance, respectively. For a one SD higher level of serum insulin (7.14 μU/ml), C-peptide (0.45 Δmol/ml), HbA1c (0.52%), and HOMA-insulin resistance (1.93), the odds ratio (95% CI) of CKD was 1.35 (1.16 to 1.57), 2.78 (2.25 to 3.42), 1.69 (1.28 to 2.23), and 1.30 (1.13 to 1.50), respectively. These findings combined with knowledge from previous studies suggest that the insulin resistance and concomitant hyperinsulinemia are presented in CKD patients without clinical diabetes. Further studies into the causality between insulin resistance and CKD are warranted. E-mail address: jhe@tulane.edu
Effects of chronic mitral regurgitation on diastolic function in isolated cardiocytes.
Authors: H Tsutsui, Y Urabe, D L Mann, H Tagawa, B A Carabello, G Cooper, M R Zile
Journal: Circulation Research (1993)

We have previously shown that chronic mitral regurgitation (MR) increases the rate of left ventricular early diastolic filling. These changes in chamber diastolic function were felt to be secondary to alterations in left ventricular loading conditions. Therefore, cellular diastolic function measured in cardiac muscle cells (cardiocytes) isolated from animals with chronic MR (absent alterations in loading conditions) was expected to be normal. However, chronic MR caused a decrease in sarcomere lengthening rate. The purpose of the current study was to define the mechanisms causing this decreased sarcomere lengthening rate in chronic MR cardiocytes and to explain the apparent dichotomy between chamber and cellular diastolic properties. Accordingly, sarcomere motion was measured using laser diffraction techniques in enzymatically isolated cardiocytes from seven control dogs and 11 dogs with chronic MR (produced by closed-chest transection of the mitral chordae). In the MR cardiocytes, there were abnormalities in cellular systolic function (decreased extent and velocity of shortening) and in cellular diastolic function (decreased velocity of sarcomere lengthening). Because studies in papillary muscles have shown that there is a direct relation between abnormal diastolic function (decreased velocity of muscle lengthening) and abnormal systolic function (decreased extent of muscle shortening), it was unclear whether the changes in cellular relaxation rate observed in chronic MR merely reflected a concomitant decrease in the extent of shortening or instead reflected an impairment in intrinsic relaxation properties. To make this distinction, the relation between relaxation velocity (measured as peak sarcomere lengthening rate) and sarcomere shortening extent was examined in MR cardiocytes and compared with that in control cardiocytes. There was a direct relation between sarcomere relaxation velocity and sarcomere shortening extent in both control and MR cardiocytes. Over a wide range of shortening extent, the slopes and y intercepts of this relation were similar in control and MR cardiocytes (slope, 27.7 sec-1 in control cells versus 28.1 sec-1 in MR cells; y intercept, -1.1 microns/sec in control cells versus -1.7 microns/sec in MR cells; p = NS). At any common shortening extent, relaxation velocity was the same in control and MR cardiocytes. To prove that this relation could detect abnormalities in the intrinsic myocardial relaxation process, interventions known to produce primary alterations in the intrinsic myocardial relaxation process were examined: the effects of hypothermia (30 degrees C) and isoproterenol (10(-6) M) on the relaxation velocity-shortening extent relation were studied in normal and MR cardiocytes.(ABSTRACT TRUNCATED AT 400 WORDS)
Hyperfunctional affections of the stato-kinetic apparatus specific to sportsmen of high performance
Authors: S. Nicolae
Journal: British Journal of Sports Medicine (1970)

The statistical analysis of the traumatic affections treated by the author during 1967 in the traumatic service of the Centre of Sports Medicine, Bucharest shows the fact that traumatic affections amount to 34.1% whereas hyperfunctional lesions to 22.9%. The author does not agree with the denomination of “sportive microtraumatisms” given to these affections because of the aetio-pathogeny and the sportive specificity of this kind of lesions. Relying on clinical history and examination; on physiopathological and especially on biochemical and histological and histochemical date, he proposes the name of hyper-functional localized affections. Among the arguments put forward by the author the following are to be retained: parallelism between biochemical data (increase of syalic acid and generally of blood mucoproteins) and histochemical aspects of tissue mucopolysaccharides of lesions (proved by microscopic sections which underwent enzymatic extractions). The author considers these affections to be expressions of some forms of overtraining, localized in the stato-kinetic apparatus, admitting as an aetio-pathogenic mechanism, the imbalance between biochemical stresses of the training effort “technopathy” and physiochemical dismetabolic and functional properties of the respective tissue, expressed by imbalance of tissue enzymes within the complex limits of the changes of overtraining.
Trends in Acute Nonvariceal Upper Gastrointestinal Bleeding in Dialysis Patients
Authors: Ju-Yeh Yang, Tsung-Chun Lee, Maria E. Montez-Rath, Jane Paik, Glenn M. Chertow, Manisha Desai, Wolfgang C. Winkelmayer
Journal: Journal of the American Society of Nephrology (2012)

Impaired kidney function is a risk factor for upper gastrointestinal (GI) bleeding, an event associated with poor outcomes. The burden of upper GI bleeding and its effect on patients with ESRD are not well described. Using data from the US Renal Data System, we quantified the rates of occurrence of and associated 30-day mortality from acute, nonvariceal upper GI bleeding in patients undergoing dialysis; we used medical claims and previously validated algorithms where available. Overall, 948,345 patients contributed 2,296,323 patient-years for study. The occurrence rates for upper GI bleeding were 57 and 328 episodes per 1000 person-years according to stringent and lenient definitions of acute, nonvariceal upper GI bleeding, respectively. Unadjusted occurrence rates remained flat (stringent) or increased (lenient) from 1997 to 2008; after adjustment for sociodemographic characteristics and comorbid conditions, however, we found a significant decline for both definitions (linear approximation, 2.7% and 1.5% per year, respectively; P<0.001). In more recent years, patients had higher hematocrit levels before upper GI bleeding episodes and were more likely to receive blood transfusions during an episode. Overall 30-day mortality was 11.8%, which declined significantly over time (relative declines of 2.3% or 2.8% per year for the stringent and lenient definitions, respectively). In summary, despite declining trends worldwide, crude rates of acute, nonvariceal upper GI bleeding among patients undergoing dialysis have not decreased in the past 10 years. Although 30-day mortality related to upper GI bleeding declined, perhaps reflecting improvements in medical care, the burden on the ESRD population remains substantial.
Effect of cA2 Anti–Tumor Necrosis Factor-α Antibody Therapy on Hematopoiesis of Patients with Myelodysplastic Syndromes
Authors: Anna Boula, Michael Voulgarelis, Stavroula Giannouli, George Katrinakis, Maria Psyllaki, Charalambos Pontikoglou, Fotini Markidou, George D. Eliopoulos, Helen A. Papadaki
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Tumor necrosis factor α (TNF-α) plays a prominent role in the pathophysiology of myelodysplastic syndromes (MDS). The aim of this study was to explore the biological and immunoregulatory effect of the treatment with the anti–tumor necrosis factor-α monoclonal antibody cA2 on bone marrow (BM) progenitor/precursor and stromal cells and lymphocyte subsets, as well as the clinical response in MDS patients. Experimental Design: Ten low-intermediate risk MDS patients received i.v. cA2 (3 mg/kg) at weeks 0, 2, 6, and 12. The number, survival, and clonogenic potential of BM progenitor/precursor cells, the hematopoiesis-supporting capacity of BM stromal cells, and the lymphocyte activation status were investigated in the patients at baseline and following treatment using flow cytometry, clonogenic assays, and long-term BM cultures (LTBMC). Clinical response was evaluated according to standardized criteria. Results: cA2 administration reduced the proportion of apoptotic and Fas+ cells in the CD34+ cell compartment (P = 0.0215 and P = 0.0344, respectively) and increased the clonogenic potential of BM mononuclear and CD34+ cells (P = 0.0399 and P = 0.0304, respectively) compared with baseline. The antibody reduced tumor necrosis factor-α levels in LTBMC supernatants (P = 0.0043) and significantly improved the hematopoiesis-supporting capacity of LTBMC adherent cells. The proportion of activated peripheral blood and BM T-lymphocytes decreased significantly after treatment, suggesting an immunomodulatory effect of cA2. Two patients displayed minor hematologic responses whereas the remaining patients displayed stable disease with no disease progression. Conclusions: The encouraging biological insights from cA2 administration may be useful in conducting further clinical trials using cA2 for selected MDS patients, particularly those with evidence of immune-mediated inhibition of hematopoiesis.
The presence of steatosis and elevation of alanine aminotransferase levels are associated with fibrosis progression in chronic hepatitis C with non-response to interferon therapy
Authors: Masayuki Kurosaki, Kotaro Matsunaga, Itsuko Hirayama, Tomohiro Tanaka, Mitsuaki Sato, Nobutoshi Komatsu, Naoki Umeda, Takanori Hosokawa, Ken Ueda, Kaoru Tsuchiya, Hiroyuki Nakanishi, Jun Itakura, Yasuhiro Asahina, Shozo Miyake, Nobuyuki Enomoto, Namiki Izumi
Journal: Journal of Hepatology (2008)
Treatment of Travelers’ Diarrhea: Randomized Trial Comparing Rifaximin, Rifaximin Plus Loperamide, and Loperamide Alone
Authors: Herbert L. Dupont, Zhi–Dong Jiang, Jaime Belkind–Gerson, Pablo C. Okhuysen, Charles D. Ericsson, Shi Ke, David B. Huang, Margaret W. Dupont, Javier A. Adachi, F. Javier De La Cabada, David N. Taylor, Sridvya Jaini, Francisco Martinez Sandoval
Journal: Clinical Gastroenterology and Hepatology (2007)
Lacrimal drainage obstruction in gastric cancer patients receiving S-1 chemotherapy
Authors: N. Kim, C. Park, D.J. Park, H.-H. Kim, S. Kim, Y.J. Kim, J.H. Kim, J.S. Lee, Y.-J. Bang, S.I. Khwarg, H. Choung, M.J. Lee, K.-W. Lee
Journal: Annals of Oncology (2012)
URI Is an Oncogene Amplified in Ovarian Cancer Cells and Is Required for Their Survival
Authors: Jean-Philippe Theurillat, Stefan Christian Metzler, Nico Henzi, Nabil Djouder, Marianne Helbling, Anna-Kathrin Zimmermann, Francis Jacob, Alex Soltermann, Rosmarie Caduff, Viola Heinzelmann-Schwarz, Holger Moch, Wilhelm Krek
Journal: Cancer Cell (2011)
When noise makes music: HIV reactivation with transcriptional noise enhancers
Authors: Xu Tan, Stephen J Elledge
Journal: Genome Medicine (2014)

Reactivating latent HIV is key to depleting the virus reservoir in AIDS patients. A recent paper has described the rationale for and discovery of a new class of drugs - transcriptional noise enhancers - that can synergize with conventional transcription activators to more effectively reactivate latently infected T cells. As well as describing a promising new strategy in the bid to find a cure for AIDS, this study more broadly highlights the utility of exploring drug combinations in treatment of human disease.
Degradation of Host MicroRNAs by Poxvirus Poly(A) Polymerase Reveals Terminal RNA Methylation as a Protective Antiviral Mechanism
Authors: Simone Backes, Jillian S. Shapiro, Leah R. Sabin, Alissa M. Pham, Ismarc Reyes, Bernard Moss, Sara Cherry, Benjamin R. tenOever
Journal: Cell Host & Microbe (2012)
The Failure of Interleukin-10–deficient Mice to Develop Airway Hyperresponsiveness Is Overcome by Respiratory Syncytial Virus Infection in Allergen–sensitized/challenged Mice
Authors: MIKA J. MÄKELÄ, ARIHIKO KANEHIRO, AZZEDDINE DAKHAMA, LARRY BORISH, ANTHONY JOETHAM, RALPH TRIPP, LARRY ANDERSON, ERWIN W. GELFAND
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Interleukin-10–deficient mice develop a robust pulmonary inflammatory response but no airway hyperresponsiveness (AHR) to inhaled methacholine (MCh) following allergen sensitization and challenge. In the present study, we investigated the effect of respiratory syncytial virus (RSV) infection on AHR and pulmonary inflammation in allergic IL-10 − / − mice. Unlike littermate control mice, RSV-infected or ovalbumin (OVA)-sensitized/challenged IL-10 − / − mice failed to develop significant AHR. In contrast, sensitized/challenged IL-10 − / − mice infected with RSV did develop AHR accompanied by increased eosinophil numbers, both in bronchoalveolar lavage (BAL) and pulmonary tissue, and mucin production in airway epithelium. The cytokine profile in OVA-sensitized/challenged IL-10 − / − mice was skewed toward a Th1 response but after RSV infection, this response was more of a Th2 type, with increased IL-5 levels in the BAL. Studies with an RSV mutant that lacks the G and SH genes showed equal enhancement of the AHR response as the parental wild-type strain, indicating that G protein is not essential to this response. These data suggest that RSV infection can overcome the failure of development of AHR in allergic IL-10 − / − mice.
PM-15 * NOTCH AND SHH SIGNALING PATHWAYS CONVERGE ON THE PRIMARY CILIUM TO PROMOTE CHOROID PLEXUS TUMOR INITIATION FROM EPITHELIAL PROGENITORS
Authors: H. Zhao, L. Li, K. Picotte, J. Wang, R. Wechsler-Reya, J. Ohli, U. Schuller
Journal: Neuro-Oncology (2015)

Choroid plexus (CP) tumors are brain neoplasms arising from CP epithelium. They occur most often in childhood and comprise 10-20% of all brain tumors in infants. While CP papilloma is benign, CP carcinoma is malignant and associated with poor prognosis. Previous studies have implicated Notch signaling in human CP tumors. However, the cell of origin and mechanisms underlying Notch-induced CP tumors remain unclear. We have developed novel mouse models of CP tumor caused by sustained expression of Notch 1 that recapitulate properties of human CP tumors with abnormal NOTCH signaling. While tumor cells in our models expressed CP markers Lmx1a and Otx2, the expression of aquaporin 1 and transthyretin, markers for differentiated CP epithelium, was absent or significantly reduced. Gene expression profiling revealed that tumor cell proliferation is accompanied by enhanced Sonic Hedgehog (Shh) signaling. Importantly, human CP tumors with abnormal NOTCH pathway activities also exhibited increased SHH signaling. Shh treatment stimulated the proliferation of Notch-induced CP tumor cells, while inhibition of Shh signaling suppressed tumor growth. Vertebrate Shh signaling is dependent on primary cilium. Unlike mature CP epithelial cells with clusters of primary cilia on cell surface, Notch-induced CP tumor cells possess a solitary primary cilium. Further analysis showed reduced expression of genes involved in multiciliate differentiation in tumor cells. Shh-driven signaling cascade in the primary cilium occured in tumor cells but not in epithelial cells. Lineage studies showed that Notch-induced CP tumor arose from mono-ciliated epithelial progenitors in roof plates characterized by elevated Notch signaling. Together, these results indicate that sustained activation of Notch signaling causes aberrant proliferation of epithelial progenitors, converting them into tumor-initiating cells that retain the ability to transduce Shh signals in the local environment and allows for Shh-driven proliferation. Our studies demonstrate Shh pathway is a potential therapeutic target for Notch-induced CP tumors.
Biomechanical Hearts
Authors: Norbert W. Guldner, Peter Klapproth, Martin Großherr, Andreas Brügge, Abdolhamid Sheikhzadeh, Ralph Tölg, Elisabeth Rumpel, Ralf Noel, Hans-H. Sievers
Journal: Circulation (2001)

As shown previously in goats, clenbuterol increased the power of electrically conditioned skeletal muscle ventricles (SMVs) of clinically relevant size (150 mL), which were constructed around a mock system. They pumped against a pressure of 60 to 70 mm Hg immediately during surgery and up to several months after, finally at >1 L/min. SMVs without clenbuterol administration failed. Thus, we expected that clenbuterol-supported SMVs might become integrated into the circulation by a 1-step operation instead of the 2-step procedure required up to now.In adult Boer goats (n=5), latissimus dorsi muscle was wrapped around a polyurethane chamber of 150 mL that was connected to the descending aorta. This muscular flow-through pumping chamber containing a stabilizing inner layer (called a biomechanical heart [BMH]) was formed and immediately made to work against a systemic load with the support of clenbuterol (5x150 microg/wk). During surgery, the mean stroke volume of BMHs was 53.8+/-22.4 mL. One month after surgery, in peripheral arterial pressure, the mean diastolic (P(MD)) and minimal diastolic (P(min)) pressures of BMH-supported heart cycles differed significantly from unsupported ones (P(MD)=+2.9+/-1.1 mm Hg [P<0.04], P(min)=-2.4+/-0.9 mm Hg [P<0.04]). After BMH-supported heart contractions, the subsequent maximal rate of pressure generation, dP/dt(max), increased by 20.5+/-8.1% (P<0.02). One BMH, catheterized 132 days after surgery, shifted a volume of 34.8 mL per beat and 1.4 L/min with a latissimus dorsi muscle of 330 g. Depending on duration of training, the percentage of myosin heavy chain type 1 ranged between 31% and 100%.Under support of clenbuterol, BMHs of a clinically relevant size can be trained effectively in the systemic circulation after a 1-step operation and offer the prospect of a sufficient volume shift and probably unloading of the left ventricle.
The metabolic advantage of tumor cells
Authors: Maurice Israël, Laurent Schwartz
Journal: Molecular Cancer (2011)

1-Oncogenes express proteins of "Tyrosine kinase receptor pathways", a receptor family including insulin or IGF-Growth Hormone receptors.Other oncogenes alter the PP2A phosphatase brake over these kinases.2-Experiments on pancreatectomized animals; treated with pure insulin or total pancreatic extracts, showed that choline in the extract, preserved them from hepatomas.Since choline is a methyle donor, and since methylation regulates PP2A, the choline protection may result from PP2A methylation, which then attenuates kinases.3-Moreover, kinases activated by the boosted signaling pathway inactivate pyruvate kinase and pyruvate dehydrogenase.In addition, demethylated PP2A would no longer dephosphorylate these enzymes.A "bottleneck" between glycolysis and the oxidative-citrate cycle interrupts the glycolytic pyruvate supply now provided via proteolysis and alanine transamination.This pyruvate forms lactate (Warburg effect) and NAD+ for glycolysis.Lipolysis and fatty acids provide acetyl CoA; the citrate condensation increases, unusual oxaloacetate sources are available.ATP citrate lyase follows, supporting aberrant transaminations with glutaminolysis and tumor lipogenesis.Truncated urea cycles, increased polyamine synthesis, consume the methyl donor SAM favoring carcinogenesis.4-The decrease of butyrate, a histone deacetylase inhibitor, elicits epigenic changes (PETEN, P53, IGFBP decrease; hexokinase, fetal-genes-M2, increase) 5-IGFBP stops binding the IGF -IGFR complex, it is perhaps no longer inherited by a single mitotic daughter cell; leading to two daughter cells with a mitotic capability.6-An excess of IGF induces a decrease of the major histocompatibility complex MHC1, Natural killer lymphocytes should eliminate such cells that start the tumor, unless the fever prostaglandin PGE2 or inflammation, inhibit them...
Key Issues in Conducting a Meta-Analysis of Gene Expression Microarray Datasets
Authors: Adaikalavan Ramasamy, Adrian Mondry, Chris C Holmes, Douglas G Altman
Journal: PLoS Medicine (2008)

have led to the generation of many highly complex datasets that often try to address similar biological questions.from independent but related studies, is a relatively inexpensive option that has the potential to increase both the statistical power and generalizability of single-study analysis.general, is desirable, and is much enhanced when raw data are available.in conducting meta-analysis of microarray datasets: (1) Identify suitable microarray studies; (2) Extract the data from studies;(3) Prepare the individual datasets; (4) Annotate the individual datasets; (5) Resolve the many-to-many relationship between probes and genes; (6) Combine the study-specific estimates; (7) Analyze, present, and interpret results.reviewing such a meta-analysis. of high-throughput biological data analysis.
Plasma osteopontin, hypoxia, and response to the hypoxia sensitiser nimorazole in radiotherapy of head and neck cancer: results from the DAHANCA 5 randomised double-blind placebo-controlled trial
Authors: Jens Overgaard, Jesper Grau Eriksen, Marianne Nordsmark, Jan Alsner, Michael R Horsman
Journal: The Lancet Oncology (2005)
Adenomatous Polyps Are Driven by Microbe-Instigated Focal Inflammation and Are Controlled by IL-10–Producing T Cells
Authors: Kristen L. Dennis, Yunwei Wang, Nichole R. Blatner, Shuya Wang, Abdulrahman Saadalla, Erin Trudeau, Axel Roers, Casey T. Weaver, James J. Lee, Jack A. Gilbert, Eugene B. Chang, Khashayarsha Khazaie
Journal: Cancer Research (2013)

Interleukin (IL)-10 is elevated in cancer and is thought to contribute to immune tolerance and tumor growth. Defying these expectations, the adoptive transfer of IL-10-expressing T cells to mice with polyposis attenuates microbial-induced inflammation and suppresses polyposis. To gain better insights into how IL-10 impacts polyposis, we genetically ablated IL-10 in T cells in APC(Δ468) mice and compared the effects of treatment with broad-spectrum antibiotics. We found that T cells and regulatory T cells (Treg) were a major cellular source of IL-10 in both the healthy and polyp-bearing colon. Notably, T cell-specific ablation of IL-10 produced pathologies that were identical to mice with a systemic deficiency in IL-10, in both cases increasing the numbers and growth of colon polyps. Eosinophils were found to densely infiltrate colon polyps, which were enriched similarly for microbiota associated previously with colon cancer. In mice receiving broad-spectrum antibiotics, we observed reductions in microbiota, inflammation, and polyposis. Together, our findings establish that colon polyposis is driven by high densities of microbes that accumulate within polyps and trigger local inflammatory responses. Inflammation, local microbe densities, and polyp growth are suppressed by IL-10 derived specifically from T cells and Tregs.