tbuckley/cabot-search huggingface dataset:
5-Aminosalicylic Acid Given in the Remission Stage of Colitis Suppresses Colitis-Associated Cancer in a Mouse Colitis Model
Authors: Ikuko Ikeda, Ayako Tomimoto, Koichiro Wada, Toshio Fujisawa, Koji Fujita, Kyoko Yonemitsu, Yuichi Nozaki, Hiroki Endo, Hirokazu Takahashi, Masato Yoneda, Masahiko Inamori, Kensuke Kubota, Satoru Saito, Yoji Nagashima, Hitoshi Nakagama, Atsushi Nakajima
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The risk of colorectal cancer is increased in patients with inflammatory bowel diseases, especially those with ulcerative colitis (UC). Although 5-aminosalicylic acid (5-ASA) is widely used in the treatment of UC to suppress the colitic inflammation, no studies have been conducted to examine the chemopreventive effect of 5-ASA, given in the remission phase of colitis, against colitis-associated cancer using animal models. We therefore investigated the possible inhibition by peroxisome proliferator-activated receptor-γ (PPARγ) ligands and 5-ASA of colitis-associated colon carcinogenesis in a mouse model. Experimental Design: A dextran sodium sulfate/azoxymethane–induced mouse colon cancer model was used, and the chemopreventive effects of 5-ASA and PPARγ ligands, given in the remission phase of colitis, against colitis-related colon carcinogenesis, were evaluated. Results: The number of neoplasms in the mice treated with 5-ASA was significantly lower than that in the control mice. In addition, the size of the neoplasms in treated mice was also significantly smaller than that in the control mice. In contrast, no significant suppression in the number or size of the tumors was observed in the mice treated with PPARγ ligands. The proliferating cell nuclear antigen–labeling index in the tumor cells of the 5-ASA–treated mice was significantly smaller than that in the control, indicating that 5-ASA reduced tumor cell proliferation. Conclusion: Our results revealed that 5-ASA given in the remission phase of colitis significantly suppressed the development of colitis-associated cancer in a mouse model, which indicates the clinical importance of adopting chemopreventive strategies even in UC patients in remission.
Glial Cell–Derived Neurotrophic Factor–Independent Ureteric Bud Outgrowth from the Wolffian Duct
Authors: Akito Maeshima, Hiroyuki Sakurai, Yohan Choi, Shinji Kitamura, Duke A. Vaughn, James B. Tee, Sanjay K. Nigam
Journal: Journal of the American Society of Nephrology (2007)

The kidney collecting duct system and the ureter derive from the ureteric bud, an outgrowth of the Wolffian duct. It is generally believed that glial cell–derived neurotrophic factor (GDNF) plays a critical role in this earliest stage of kidney development, but 30 to 50% of knockout mice that lack
Is it the true incidence of IgE-cow's milk allergy (CMA) or CMA or IgE-CMA in some countries and CMA in others
Authors: Y. Katz, A. Nowak-Wegrzyn, K. E. Grimshaw, K. Beyer, L. Grabenhenrich, T. Keil, A. B. Sprikkelman, G. Roberts
Journal: Allergy (2015)
Imaging Classification of Autosomal Dominant Polycystic Kidney Disease
Authors: María V. Irazabal, Laureano J. Rangel, Eric J. Bergstralh, Sara L. Osborn, Amber J. Harmon, Jamie L. Sundsbak, Kyongtae T. Bae, Arlene B. Chapman, Jared J. Grantham, Michal Mrug, Marie C. Hogan, Ziad M. El-Zoghby, Peter C. Harris, Bradley J. Erickson, Bernard F. King, Vicente E. Torres
Journal: Journal of the American Society of Nephrology (2014)

The rate of renal disease progression varies widely among patients with autosomal dominant polycystic kidney disease (ADPKD), necessitating optimal patient selection for enrollment into clinical trials. Patients from the Mayo Clinic Translational PKD Center with ADPKD (n=590) with computed tomography/magnetic resonance images and three or more eGFR measurements over ≥6 months were classified radiologically as typical (n=538) or atypical (n=52). Total kidney volume (TKV) was measured using stereology (TKVs) and ellipsoid equation (TKVe). Typical patients were randomly partitioned into development and internal validation sets and subclassified according to height-adjusted TKV (HtTKV) ranges for age (1A-1E, in increasing order). Consortium for Radiologic Imaging Study of PKD (CRISP) participants (n=173) were used for external validation. TKVe correlated strongly with TKVs, without systematic underestimation or overestimation. A longitudinal mixed regression model to predict eGFR decline showed that log2HtTKV and age significantly interacted with time in typical patients, but not in atypical patients. When 1A-1E classifications were used instead of log2HtTKV, eGFR slopes were significantly different among subclasses and, except for 1A, different from those in healthy kidney donors. The equation derived from the development set predicted eGFR in both validation sets. The frequency of ESRD at 10 years increased from subclass 1A (2.4%) to 1E (66.9%) in the Mayo cohort and from 1C (2.2%) to 1E (22.3%) in the younger CRISP cohort. Class and subclass designations were stable. An easily applied classification of ADPKD based on HtTKV and age should optimize patient selection for enrollment into clinical trials and for treatment when one becomes available.
Sequence evolution in bacterial endosymbionts having extreme base compositions
Authors: M. A. Clark, N. A. Moran, P. Baumann
Journal: Molecular Biology and Evolution (1999)

A major limitation on ability to reconstruct bacterial evolution is the lack of dated ancestors that might be used to evaluate and calibrate molecular clocks. Vertically transmitted symbionts that have cospeciated with animal hosts offer a firm basis for calibrating sequence evolution in bacteria, since fossils of the hosts can be used to date divergence events. Sequences for a functionally diverse set of genes have been obtained for bacterial endosymbionts (Buchnera) from two pairs of aphid host species, each pair diverging 50-70 MYA. Using these dates and estimated numbers of Buchnera generations per year, we calculated rates of base substitution for neutral and selected sites of protein-coding genes and overall rates for rRNA genes. Buchnera shows homogeneity among loci with regard to synonymous rate. The Buchnera synonymous rate is about twice that for low-codon-bias genes of Escherichia coli-Salmonella typhimurium on an absolute timescale, and fourfold higher on a generational timescale. Nonsynonymous substitutions show a greater rate disparity in favor of Buchnera, a result consistent with a genomewide decrease in selection efficiency in Buchnera. Ratios of synonymous to nonsynonymous substitutions differ for the two pairs of Buchnera, indicating that selection efficiency varies among lineages. Like numerous other intracellular bacteria, such as Rickettsia and Wolbachia, Buchnera has accumulated amino acids with codons rich in A or T. Phylogenetic reconstruction of amino acid replacements indicates that replacements yielding increased A + T predominated early in the evolution of Buchnera, with the trend slowing or stopping during the last 50 Myr. This suggests that base composition in Buchnera has approached a limit enforced by selective constraint acting on protein function.
Is This Patient Having a Myocardial Infarction?
Authors: Akbar A. Panju
Journal: JAMA (1998)

When faced with a patient with acute chest pain, clinicians must distinguish myocardial infarction (MI) from all other causes of acute chest pain. If MI is suspected, current therapeutic practice includes deciding whether to administer thrombolysis or primary percutaneous transluminal coronary angioplasty and whether to admit patients to a coronary care unit. The former decision is based on electrocardiographic (ECG) changes, including ST-segment elevation or left bundle-branch block, the latter on the likelihood of the patient's having unstable high-risk ischemia or MI without ECG changes. Despite advances in investigative modalities, a focused history and physical examination followed by an ECG remain the key tools for the diagnosis of MI. The most powerful features that increase the probability of MI, and their associated likelihood ratios (LRs), are new ST-segment elevation (LR range, 5.7-53.9); new Q wave (LR range, 5.3-24.8); chest pain radiating to both the left and right arm simultaneously (LR, 7.1); presence of a third heart sound (LR, 3.2); and hypotension (LR, 3.1). The most powerful features that decrease the probability of MI are a normal ECG result (LR range, 0.1-0.3), pleuritic chest pain (LR, 0.2), chest pain reproduced by palpation (LR range, 0.2-0.4), sharp or stabbing chest pain (LR, 0.3), and positional chest pain (LR, 0.3). Computer-derived algorithms that depend on clinical examination and ECG findings might improve the classification of patients according to the probability that an MI is causing their chest pain.
Hemodynamics after orthotopic liver transplantation: Study of associated factors and long-term effects
Authors: Adrian Gadano, Antoine Hadengue, Jean Jacques Widmann, Florence Vachiery, Richard Moreau, Song Yang, Thierry Soupison, Philippe Sogni, Claude Degott, François Durand, Jacques Bernuau, Jacques Belghiti, Serge Erlinger, Jean Pierre Benhamou, Didier Lebrec
Journal: Hepatology (1995)

Among 68 liver transplant recipients, 190 hemodynamic studies were performed to evaluate the role of sepsis, anemia, acute graft rejection, and persistent portosystemic shunts. The hemodynamic outcome after orthotopic liver transplantation (OLT) in stable patients was also determined. Patients with sepsis showed a significant increase in cardiac index (5.1 +/- 0.9 vs. 3.4 +/- 0.7 L/min m2) and hepatic venous pressure gradient (6.3 +/- 2.9 vs. 3.3 +/- 2.1 mm Hg), compared with patients without sepsis. Cardiac index was higher in patients with, than in patients without, anemia (4.1 +/- 0.6 vs. 3.0 +/- 0.6 L/min m2). The hepatic venous pressure gradient was higher in patients with than in patients without acute graft rejection (5.1 +/- 2.9 vs. 2.6 +/- 1.2 mm Hg). Among patients with acute rejection, the hepatic venous pressure gradient was higher in patients with severe rejection than in those with moderate or mild rejection (7.2 +/- 3.3 vs. 4.6 +/- 2.4 and 2.8 +/- 0.9 mm Hg). In the postoperative period, in patients undergoing transplantation for acute liver failure, the hepatic blood flow was normal and significantly lower than in patients receiving transplant for cirrhosis (1.15 +/- 0.37 vs. 1.96 +/- 0.71 L/min). In patients undergoing transplantation for cirrhosis, cardiac index, azygos, and hepatic blood flows significantly decreased after 1 year compared with the first 6 postoperative months. Multivariate analysis showed that sepsis, anemia, and time after OLT were independent variables influencing cardiac index. Sepsis, time after OLT, and the existence of portosystemic shunts were independent variables influencing hepatic blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)
Area-Level Socioeconomic Status and Incidence of Abnormal Glucose Metabolism
Authors: Emily D. Williams, Dianna J. Magliano, Paul Z. Zimmet, Anne M. Kavanagh, Christopher E. Stevenson, Brian F. Oldenburg, Jonathan E. Shaw
Journal: Diabetes Care (2012)

OBJECTIVE To examine the role of area-level socioeconomic status (SES) on the development of abnormal glucose metabolism (AGM) using national, population-based data. RESEARCH DESIGN AND METHODS The Australian Diabetes, Obesity and Lifestyle (AusDiab) study is a national, population-based, longitudinal study of adults aged ≥25 years. A sample of 4,572 people provided complete baseline (1999 to 2000) and 5-year follow-up (2004 to 2005) data relevant for these analyses. Incident AGM was assessed using fasting plasma glucose and 2-h plasma glucose from oral glucose tolerance tests, and demographic, socioeconomic, and behavioral data were collected by interview and questionnaire. Area SES was defined using the Index of Relative Socioeconomic Disadvantage. Generalized linear mixed models were used to examine the relationship between area SES and incident AGM, with adjustment for covariates and correction for cluster design effects. RESULTS Area SES predicted the development of AGM, after adjustment for age, sex, and individual SES. People living in areas with the most disadvantage were significantly more likely to develop AGM, compared with those living in the least deprived areas (odds ratio 1.53; 95% CI 1.07–2.18). Health behaviors (in particular, physical activity) and central adiposity appeared to partially mediate this relationship. CONCLUSIONS Our findings suggest that characteristics of the physical, social, and economic aspects of local areas influence diabetes risk. Future research should focus on identifying the aspects of local environment that are associated with diabetes risk and how they might be modified.
EFFECT OF NUTRITION ON THE RESISTANCE OF MICE TO ENDOTOXIN AND ON THE BACTERICIDAL POWER OF THEIR TISSUES
Authors: Rene J. Dubos, Russell W. Schaedler
Journal: The Journal of Experimental Medicine (1959)

Mice on inadequate nutritional regimens were found to be more susceptible to various bacterial diseases than mice fed a complete diet containing 15 to 20 per cent casein. The tests of susceptibility included: (a) infections with virulent bacteria; (b) injection of large doses of avirulent coagulase-negative staphylococci; and (c) lethal effects of bacterial endotoxins. The infection-enhancing effect of nutritional deficiencies could be rendered even more striking by administering the infective inoculum simultaneously with a sublethal dose of endotoxin. Despite their great susceptibility to infection, malnourished animals retained much of their ability to eliminate bacteria from the blood, liver, spleen, kidneys, and lungs, at least during the early phases of the infectious processes. This was true even when the animals had received endotoxin simultaneously with the infective dose. The results suggest that under the conditions of the present study, the nutritional state influenced the outcome of infection not primarily by affecting the fate of the pathogens in vivo, but rather by modifying the ability of the host to resist their toxic effects.
Automated Detection and Classification of Type 1 Versus Type 2 Diabetes Using Electronic Health Record Data
Authors: Michael Klompas, Emma Eggleston, Jason McVetta, Ross Lazarus, Lingling Li, Richard Platt
Journal: Diabetes Care (2012)

To create surveillance algorithms to detect diabetes and classify type 1 versus type 2 diabetes using structured electronic health record (EHR) data.We extracted 4 years of data from the EHR of a large, multisite, multispecialty ambulatory practice serving ∼700,000 patients. We flagged possible cases of diabetes using laboratory test results, diagnosis codes, and prescriptions. We assessed the sensitivity and positive predictive value of novel combinations of these data to classify type 1 versus type 2 diabetes among 210 individuals. We applied an optimized algorithm to a live, prospective, EHR-based surveillance system and reviewed 100 additional cases for validation.The diabetes algorithm flagged 43,177 patients. All criteria contributed unique cases: 78% had diabetes diagnosis codes, 66% fulfilled laboratory criteria, and 46% had suggestive prescriptions. The sensitivity and positive predictive value of ICD-9 codes for type 1 diabetes were 26% (95% CI 12-49) and 94% (83-100) for type 1 codes alone; 90% (81-95) and 57% (33-86) for two or more type 1 codes plus any number of type 2 codes. An optimized algorithm incorporating the ratio of type 1 versus type 2 codes, plasma C-peptide and autoantibody levels, and suggestive prescriptions flagged 66 of 66 (100% [96-100]) patients with type 1 diabetes. On validation, the optimized algorithm correctly classified 35 of 36 patients with type 1 diabetes (raw sensitivity, 97% [87-100], population-weighted sensitivity, 65% [36-100], and positive predictive value, 88% [78-98]).Algorithms applied to EHR data detect more cases of diabetes than claims codes and reasonably discriminate between type 1 and type 2 diabetes.
High-frequency ventilation augments the effect of inhaled nitric oxide in persistent pulmonary hypertension of the newborn
Authors: T Hoehn, M Krause, R Hentschel
Journal: European Respiratory Journal (1998)

Does inhaled nitric oxide (iNO) during high-frequency ventilation (HFV) lead to a more pronounced improvement in oxygenation than iNO during conventional ventilation? We report two cases of newborn infants with profound hypoxaemia, who did not respond with an increase in arterial oxygenation following iNO therapy during conventional mechanical ventilation. The first infant was a term neonate with persistent pulmonary hypertension of the newborn (PPHN) following postnatal hypoxia, the second patient a premature infant of 29 weeks of gestation with PPHN secondary to lung hypoplasia and perinatal asphyxia. After the initial failure of iNO we switched both neonates to HFV without NO, which did not lead to a significant improvement of oxygenation in either case. Shortly after the initiation of HFV a second trial of iNO was started. Both infants responded favourably to iNO with a marked and sustained increase in arterial oxygenation and absent right-to-left shunting via the ductus arteriosus and the foramen ovale. We conclude that the favourable response to inhaled nitric oxide is dependent on the degree of lung expansion and is more readily achieved by the use of high-frequency ventilation than conventional ventilation.
Tumor cell-derived PDGF-B potentiates mouse mesenchymal stem cells-pericytes transition and recruitment through an interaction with NRP-1
Authors: Kakali Dhar, Gopal Dhar, Monami Majumder, Inamul Haque, Smita Mehta, Peter J Van Veldhuizen, Sushanta K Banerjee, Snigdha Banerjee
Journal: Molecular Cancer (2010)

Abstract Background New blood vessel formation, or angiogenic switch, is an essential event in the development of solid tumors and their metastatic growth. Tumor blood vessel formation and remodeling is a complex and multi-step processes. The differentiation and recruitment of mural cells including vascular smooth muscle cells and pericytes are essential steps in tumor angiogenesis. However, the role of tumor cells in differentiation and recruitment of mural cells has not yet been fully elucidated. This study focuses on the role of human tumor cells in governing the differentiation of mouse mesenchymal stem cells (MSCs) to pericytes and their recruitment in the tumor angiogenesis process. Results We show that C3H/10T1/2 mouse embryonic mesenchymal stem cells, under the influence of different tumor cell-derived conditioned media, differentiate into mature pericytes. These differentiated pericytes, in turn, are recruited to bind with capillary-like networks formed by endothelial cells on the matrigel under in vitro conditions and recruited to bind with blood vessels on gel-foam under in vivo conditions. The degree of recruitment of pericytes into in vitro neo-angiogenesis is tumor cell phenotype specific. Interestingly, invasive cells recruit less pericytes as compared to non-invasive cells. We identified tumor cell-secreted platelet-derived growth factor-B (PDGF-B) as a crucial factor controlling the differentiation and recruitment processes through an interaction with neuropilin-1 (NRP-1) in mesenchymal stem cells. Conclusion These new insights into the roles of tumor cell-secreted PDGF-B-NRP-1 signaling in MSCs-fate determination may help to develop new antiangiogenic strategies to prevent the tumor growth and metastasis and result in more effective cancer therapies.
Mortality associated with HIV-1 infection over five years in a rural Ugandan population: cohort study
Authors: A. J Nunn, D. W Mulder, A. Kamali, A. Ruberantwari, J.-F. Kengeya-Kayondo, J. Whitworth
Journal: BMJ (1997)

<h3>Abstract</h3> <b>Objective</b>: To assess the impact of HIV-1 infection on mortality over five years in a rural Ugandan population. <b>Design</b>: Longitudinal cohort study followed up annually by a house to house census and medical survey. <b>Setting</b>: Rural population in south west Uganda. <b>Subjects</b>: About 10 000 people from 15 villages who were enrolled in 1989–90 or later. <b>Main outcome measures</b>: Number of deaths from all causes, death rates, mortality fraction attributable to HIV-1 infection. <b>Results</b>: Of 9777 people resident in the study area in 1989-90, 8833 (90%) had an unambiguous result on testing for HIV-1 antibody; throughout the period of follow up adult seroprevalence was about 8%. During 35 083 person years of follow up, 459 deaths occurred, 273 in seronegative subjects and 186 in seropositive subjects, corresponding to standardised death rates of 8.1 and 129.3 per 1000 person years. Standardised death rates for adults were 10.4 (95% confidence interval 9.0 to 11.8) and 114.0 (93.2 to 134.8) per 1000 person years respectively. The mortality fraction attributable to HIV-1 infection was 41% for adults and was in excess of 70% for men aged 25–44 and women aged 20–44 years. Median survival from time of enrolment was less than three years in subjects aged 55 years or more who were infected with HIV-1. Life expectancy from birth in the total population resident at any time was estimated to be 42.5 years (41.4 years in men; 43.5 years in women), which compares with 58.3 years (56.5 years in men; 60.5 years in women) in people known to be seronegative. <b>Conclusions</b>: These data confirm that in a rural African population HIV-1 infection is associated with high death rates and a substantial reduction in life expectancy. <h3>Key messages</h3> Comparatively few data exist on mortality associated with HIV-1 in sub-Saharan Africa Adults positive for HIV-1 in a rural Ugandan population with a prevalence of infection of 8% were more than 10 times more likely to die over a 5 year period than those negative for HIV-1 Over 40% of all deaths in adults were attributable to HIV-1 infection, the percentage in young adults aged 25–44 being in excess of 70% Life expectancy is estimated to have declined from 58.6 to 42.5 years as a consequence of the AIDS epidemic
MOLECULAR DETERMINANTS OF DRUG BINDING AND ACTION ON L-TYPE CALCIUM CHANNELS
Authors: Gregory H. Hockerman, Blaise Z. Peterson, Barry D. Johnson, and, William A. Catterall
Journal: The Annual Review of Pharmacology and Toxicology (1997)

▪ Abstract The crucial role of L-type Ca 2+ channels in the initiation of cardiac and smooth muscle contraction has made them major therapeutic targets for the treatment of cardiovascular disease. L-type channels share a common pharmacological profile, including high-affinity voltage- and frequency-dependent block by the phenylalkylamines, the benz(othi)azepines, and the dihydropyridines. These drugs are thought to bind to three separate receptor sites on L-type Ca 2+ channels that are allosterically linked. Results from different experimental approaches implicate the IIIS5, IIIS6, and IVS6 transmembrane segments of the α 1 subunits of L-type Ca 2+ channels in binding of all three classes of drugs. Site-directed mutagenesis has identified single amino acid residues within the IIIS5, IIIS6, and IVS6 transmembrane segments that are required for high-affinity binding of phenylalkylamines and/or dihydropyridines, providing further support for identification of these transmembrane segments as critical elements of the receptor sites for these two classes of drugs. The close proximity of the receptor sites for phenylalkylamines, benz(othi)azepines, and dihydropyridines raises the possibility that individual amino acid residues may be required for high-affinity binding of more than one of these ligands. Therefore, we suggest that phenylalkylamines and dihydropyridines bind to different faces of the IIIS6 and IVS6 transmembrane segments and, in some cases, bind to opposite sides of the side chains of the same amino acid residues. The results support the domain interface model for binding and channel modulation by these three classes of drugs.