tbuckley/cabot-search huggingface dataset:
Glucose and Insulin Measurements from the Oral Glucose Tolerance Test and Mortality Prediction
Authors: E. Jeffrey Metter, B. Gwen Windham, Marcello Maggio, Eleanor M. Simonsick, Shari M. Ling, Josephine M. Egan, Luigi Ferrucci
Journal: Diabetes Care (2008)

To verify what information from oral glucose tolerance tests (OGTTs) independently predicts mortality.A total of 1,401 initially nondiabetic participants from the Baltimore Longitudinal Study of Aging aged 17-95 years underwent one or more OGTTs (median 2, range 1-8), with insulin and glucose measurements taken every 20 min over the course of 2 h included in this study. Proportional hazards using the longitudinally collected data and Bayesian model averaging were used to examine the association of OGTT measurements individually and grouped with mortality, adjusting for covariates.Participants were followed for a median 20.3 years (range 0.5-40). The first-hour OGTT glucose and insulin levels increased only modestly with age, whereas levels during the second hour increased 4% per decade. Individually, 100- and 120-min glucose measures and fasting and 100-min insulin levels were all independent predictors of mortality. When all measures were considered together, only higher 120-min glucose was a significant independent risk factor for mortality.The steeper rise with age of the OGTT 2-h glucose values and the prognostic primacy of the 120-min glucose value for mortality is consistent with previous reports and suggests the value of using the OGTT in clinical practice.
Effect of Prenatal Drugs on the Behavior of the Neonate
Authors: T. BERRY BRAZELTON
Journal: American Journal of Psychiatry (1970)

The author outlines some of the intrauterine influences on neonatal behavior. Sex hormones used therapeutically in pregnancy may critically alter the genotype's sexual expression as well as its behavior. Dietary inadequacy in early fetal life may change the number and size of the infant's brain cells. Drug abuse by the mother produces chromosomal flaws as well as withdrawal symptoms in the newborn. Tranquilizers and premedications given mothers during delivery affect the neonate's initial weight gain and his response to nursing and early learning tasks.
Effects of Acute Administration of Corticosteroids during Mechanical Ventilation on Rat Diaphragm
Authors: Karen Maes, Dries Testelmans, Pascal Cadot, Keith Deruisseau, Scott K Powers, Marc Decramer, Ghislaine Gayan-Ramirez
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Mechanical ventilation is known to induce ventilator-induced diaphragm dysfunction. Patients submitted to mechanical ventilation often receive massive doses of corticosteroids that may cause further deterioration of diaphragm function.To examine whether the combination of 24 hours of controlled mechanical ventilation with corticosteroid administration would exacerbate ventilator-induced diaphragm dysfunction.Rats were randomly assigned to a group submitted to 24 hours of controlled mechanical ventilation receiving an intramuscular injection of saline or 80 mg/kg methylprednisolone, a group submitted to 24 hours of spontaneous breathing receiving saline, or methylprednisolone and a control group.The diaphragm force-frequency curve was shifted downward in the mechanical ventilation group, but this deleterious effect was prevented when corticosteroids were administered. Diaphragm cross-sectional area of type I fibers was similarly decreased in both mechanical ventilation groups while atrophy of type IIx/b fibers was attenuated after corticosteroid administration. The mechanical ventilation-induced reduction in diaphragm MyoD and myogenin protein expression was attenuated after corticosteroids. Plasma cytokine levels were unchanged while diaphragm lipid hydroperoxides were similarly increased in both mechanical ventilation groups. Diaphragmatic calpain activity was significantly increased in the mechanical ventilation group, but calpain activation was abated with corticosteroid administration. Inverse correlations were found between calpain activity and diaphragm force.A single high dose of methylprednisolone combined with controlled mechanical ventilation protected diaphragm function from the deleterious effects of controlled mechanical ventilation. Inhibition of the calpain system is most likely the mechanism by which corticosteroids induce this protective effect.
Regulation of calcium pump function in back inhibited vesicles by calcium-ATPase ligands
Authors: P. Korge, K. B Campbell
Journal: Cardiovascular Research (1995)

Objective: The aim was to evaluate the effect of changes in substrate-product concentrations of the overall sarcoplasmic reticular Ca2+-ATPase reactions on calcium pump function with an emphasis on those factors that modify back inhibition of the pump by intrareticular free calcium. Methods: Sarcoplasmic reticular vesicles were isolated from the rabbit heart. Calcium uptake by the vesicles was measured with a calcium sensitive minielectrode and was related to ATPase activity, which was measured by the rate of inorganic phosphate (Pi) production or NADH oxidation. Back inhibition was varied by changing [oxalate]. Results: At the high level of back inhibition and low calcium transport efficiency, calcium uptake by sarcoplasmic reticulum was stimulated by pH decrease, hydrophobic compounds, dimethyl sulphoxide, and ATP regeneration. These factors apparently modify either calcium binding to the low affinity binding site of Ca2+-ATPase or the effect derived from the binding of calcium to these sites. Under conditions where back inhibition was avoided and calcium transport efficiency was high, the same factors had a depressive effect on calcium uptake. Inorganic phosphate had a dual effect on the rate of calcium uptake supported by low [oxalate]: Pi < 2–3 mM strongly inhibited calcium uptake while further increase in [Pi] reversed this inhibition. At the lower level of back inhibition higher [Pi] was required to inhibit calcium transport. Conclusions: Changes in [H+], [ADP], and [Pi] can significantly affect calcium pump function, but the effect is dependent on the extent of back inhibition of calcium transport. Changes in the sarcoplasmic reticular Ca2+-ATPase environment which mimic those expected to take place at the start of reperfusion (pH increase to 7.0–7.1, high myoplasmic [Ca2+]) may have a depressive effect on the efficiency of calcium transport, provided that intrareticular free calcium is increased. Under those conditions factors able to decrease the inhibitory effect derived from the calcium binding to the low affinity binding sites are expected to improve the efficiency of calcium transport.
Abstract 2759: Association between genetic variations in DNA damage response pathways and risk for gene methylation in sputum from smokers
Authors: Shuguang Leng, Christine A. Stidley, Randall P. Willink, Yushi Liu, Maria A. Picchi, David Van Den Berg, Frank D. Gilliland, Richard E. Crowell, Steven A. Belinsky
Journal: Cancer Research (2011)

Abstract The detection of gene promoter hypermethylation in sputum containing exfoliated epithelial cells is a promising biomarker for detecting early incident lung cancer. Therefore, identifying factors that influence the propensity for this epigenetic process throughout the respiratory epithelium is a high priority. The genes and the pathways they modulate underlying the inter-individual susceptibility to DNA methylation remain largely elusive. Accumulating evidence from our group and others implicate DNA damage as an important step in the acquisition of de novo methylation. We hypothesized that genetic variations in genes (n=66) involved in carcinogen metabolism and DNA damage response, including DNA damage repair, cell cycle control, apoptosis, and methylation related pathways will be associated with gene methylation in sputum from lung-cancer free smokers. Three databases including HapMap Stage I database, University of Southern California DNA repair and Children Pulmonary Function Development Oligo Pool Assay (OPA) database, and NIBC dbSNPs database were used to select a comprehensive set of SNPs (OPA1, n=1536) to capture the major genetic variations in these genes. A pilot study for testing the association between these SNPs and risk for methylation was conducted in a subset of people (n=261) selected from Lovelace Smokers Cohort (LSR) based on their methylation index (8-gene panel). Two gene-based analyses were conducted to rank the genes and 683 tagging SNPs from the top 42 genes were selected based on the OPA1 and the HapMap Stage II databases and genotyped in all people (n=1177) with methylation data (12-gene panel) in baseline sputum samples in LSR. The effect of SNPs was tested under an additive inheritance model. A reproducible association was identified in SNPs from the TP53, GSTP1, LIG1, CASP8, BOK, and PMAIP1 genes between the pilot study and the entire study. Ongoing functional studies reveled an association between genotype and expression of LIG1 in bronchial epithelial cells from smokers. This study identified six genes involved in carcinogen detoxification and DNA damage response that were associated with risk for gene methylation in sputum from smokers. (Supported from National Cancer Institute R01 CA097356 and the State of New Mexico as a direct appropriation from the Tobacco Settlement Fund) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2759. doi:10.1158/1538-7445.AM2011-2759
Integrating Health Care to Meet the Needs of the Mother–Infant Pair: A Call for Papers for Year 3 of the Maternal Health Task Force–PLOS Collection
Authors: Kate Mitchell, Mary Nell Wegner, Ana Langer
Journal: PLoS Medicine (2013)

The Maternal Health Task Force (MHTF) and PLOS Medicine issue the call for papers for Year 3 of the MHTF-PLOS Collection: Integrating Health Care to Meet the Needs of the Mother–Infant Pair. Please see later in the article for the Editors' Summary
Voluntary Imprisonment: Its Usefulness in the Rehabilitation of Criminal Offenders
Authors: NORMAN I. BARR
Journal: American Journal of Psychiatry (1967)

The author suggests that voluntary admission of prison inmates would offer advantages similar to those relating to voluntary admission of mental patients. Such a plan, he feels, would delegate to the offender an active role in his own rehabilitation, reduce his alienation from society, and would result in public acknowledgment of the responsibility of penal institutions to encourage a rehabilitative approach and develop a therapeutic milieu.
A SALL4/MLL/HOXA9 pathway in murine and human myeloid leukemogenesis
Authors: Ailing Li, Youyang Yang, Chong Gao, Jiayun Lu, Ha-Won Jeong, Bee H. Liu, Ping Tang, Xiaopan Yao, Donna Neuberg, Gang Huang, Daniel G. Tenen, Li Chai
Journal: Journal of Clinical Investigation (2013)

The embryonic self-renewal factor SALL4 has been implicated in the development of human acute myeloid leukemia (AML). Transgenic mice expressing the human SALL4B allele develop AML, which indicates that this molecule contributes to leukemia development and maintenance. However, the underlying mechanism of SALL4-dependent AML progression is unknown. Using SALL4B transgenic mice, we observed that HoxA9 was significantly upregulated in SALL4B leukemic cells compared with wild-type controls. Downregulation of HoxA9 in SALL4B leukemic cells led to decreased replating capacity in vitro and delayed AML development in recipient mice. In primary human AML cells, downregulation of SALL4 led to decreased HOXA9 expression and enhanced apoptosis. We found that SALL4 bound a specific region of the HOXA9 promoter in leukemic cells. SALL4 overexpression led to enhanced binding of histone activation markers at the HOXA9 promoter region, as well as increased HOXA9 expression in these cells. Furthermore, we observed that SALL4 interacted with mixed-lineage leukemia (MLL) and co-occupied the HOXA9 promoter region with MLL in AML leukemic cells, which suggests that a SALL4/MLL pathway may control HOXA9 expression. In summary, our findings revealed a molecular mechanism for SALL4 function in leukemogenesis and suggest that targeting of the SALL4/MLL/HOXA9 pathway would be an innovative approach in treating AML.
OC-010 Endoscopic Resection Of Duodenal Adenomas – Comparison Of Safety And Efficacy Between Sporadic Adenomas And Adenomas In Fap
Authors: P Mundre, L Smith, A Rehman, B Rembacken
Journal: Gut (2014)

<h3>Introduction</h3> Although there is a low risk of malignant conversion of duodenal polyps in FAP, EMR is often considered. However, few studies have looked at the safety and efficacy of EMR. We compared the outcome of duodenal EMR’s in patients with FAP vs sporadic adenomas. To our knowledge, this is the largest series of duodenal EMRs that is published so far.<sup>1</sup> <h3>Methods</h3> We looked at Clinical records of all patients who underwent endoscopic resections for duodenal adenomas at Leeds in a 10 year period. <h3>Results</h3> A total of 49 sporadic adenomas were resected (in 51 patients) and 44 FAP related (in 22 patients). Most lesions appeared either sessile (43) or flat elevated (48). The average size of the FAP related polyps was 16.9 vs. 20.7 mm in sporadic lesions. Most were removed by standard EMR (n = 82) rather than the strip biopsy technique (n = 9). Two procedures failed and no follow-up data was available after the resection of 2 sporadic polyps. The final histology of the lesions were; TA+LGD (76), TA+HGD (13), adenocarcinoma (2) and 2 polyps were not retrieved. In 11 lesions, there was a change in the histological grade after resection. There were 4 perforations (4.3%), 3 were managed surgically. 12 patients (13%) were readmitted with significant late GI bleeding and 8 patients required endoscopic therapy and transfusion. There was no significant difference in the success rates in the two groups (19/44 vs. 32/49) p value 0.94). However, the resection of polyps ≥2 cm were significantly more likely to be associated with a complication (7/59 vs. 8/19 p = 0.02). There was no difference in the risk of complications with the polyp location, ASA status, Spigelman score or patient age. Amongst the FAP polyps, polyps &gt;20 mm were significantly more likely to have local recurrence (3/6 vs 3/31 p value 0.04). There was no difference in the chances of success of the resection with the growth pattern, the location of the polyp or the Spigelman score. <h3>Conclusion</h3> Duodenal EMR is hazardous, particularly when lesions 2 cm or larger are resected. However, there was no significant difference in the hazards or success rates between the two groups. Most FAP patients had further neoplasia on follow up, but this is due to the fact that many of the adenomas were not resected /treated in the first sitting. <h3>Reference</h3> 1 Basford P, Bhandari P. Endoscopic management of nonampullary duodenal polyps. <i>Therap Adv Gastroenterol</i>. 2012 March; 5(2):127–138 <h3>Disclosure of Interest</h3> None Declared.
A novel CDK inhibitor, CYC202 (R-roscovitine), overcomes the defect in p53-dependent apoptosis in B-CLL by down-regulation of genes involved in transcription regulation and survival
Authors: Azra J. Alvi, Belinda Austen, Victoria J. Weston, Christopher Fegan, David MacCallum, Athos Gianella-Borradori, David P. Lane, Mike Hubank, Judith E. Powell, Wenbin Wei, A. Malcolm R. Taylor, Paul A. H. Moss, Tatjana Stankovic
Journal: Blood (2005)
Regulation of endothelin-1 synthesis in human pulmonary arterial smooth muscle cells effects of transforming growth factor-β and hypoxia
Authors: B Markewitz
Journal: Cardiovascular Research (2001)

Objective: Endothelin-1 (ET-1) potently regulates pulmonary vascular tone and promotes vascular smooth muscle cell growth. Clinical and animal studies implicate increased ET-1 production in the pathogenesis of primary and secondary pulmonary hypertension. Although pulmonary arterial smooth muscle cells (PASMCs) synthesize ET-1 under basal conditions, it is unknown whether factors that may be important in pulmonary hypertension, such as transforming growth factor-β (TGF-β) or hypoxia, augment ET-1 production by these cells. Methods: We determined the effect of TGF-β and hypoxia on ET-1 release and preproET-1 mRNA from cultured rat and human PASMCs. Results: In the basal state, rat and human PASMCs synthesize, on average (mean±S.E.M.), 872±114 and 563±57 pg ET-1/mg cell protein over 24 h, respectively, a level that causes autocrine and paracrine effects in other tissues. TGF-β significantly increases the expression of preproET-1 mRNA and ET-1 production by both rat and human PASMCs. Hypoxia for 24 h, however, does not affect ET-1 release from rat or human PASMCs. Conclusions: Cultured rat and human PASMCs are a source of ET-1 production. Enhanced ET-1 release from PASMCs may contribute to the pathophysiology of TGF-β-induced pulmonary hypertension. ET-1 production by PASMCs is unlikely to contribute to the role of ET-1 in hypoxia-induced pulmonary vasoconstriction.
Deregulated Intracellular Signaling by Mutated c-CBL in Myeloid Neoplasms
Authors: Seishi Ogawa, Lee-Yung Shih, Takahiro Suzuki, Makoto Otsu, Hiromitsu Nakauchi, H. Phillip Koeffler, Masashi Sanada
Journal: Clinical Cancer Research (2010)

c-CBL encodes a 120-kDa protein involved in intracellular signal transduction in a wide variety of cell types. Recently, frequent mutations of c-CBL have been reported in myeloid neoplasms showing both myelodysplastic and myeloproliferative features, in which most mutations are present in a homozygous state, as a result of allelic conversion in 11q. c-CBL has ubiquitin E3 ligase activity for a wide variety of tyrosine kinases, and thereby, negatively regulates tyrosine kinase signaling. Accordingly, c-CBL seems to have tumor suppressor functions, loss of which promotes tumorigenesis. On the other hand, once mutated, it is converted to an oncogenic protein and commits to myeloid leukemogenesis through a kind of gain of function causing aberrant signal transduction. The inhibition of mutant CBL protein or signaling pathways that it activates would have a role in therapeutics of myeloid neoplasms with CBL mutations.
Quantification of a major bovine allergen by a two‐site immunometric assay based on monoclonal antibodies
Authors: J. Ylönen, T. Virtanen, M. Rytkönen, R. Mäntyjärvi
Journal: Allergy (1994)

A two‐site immunometric assay based on monoclonal antibodies (mAb) was developed for the measurement of a 20‐kDa major allergen of cow. The sensitivity of this assay was (BDA20) 1 ng/ml. It was used to measure airborne allergen concentrations in 10 Finnish cowsheds. The mean concentration of the BDA20 measured at two stationary sites was 280 ng/m 3 . Concentrations varied more than 10‐fold among cowsheds (54–804 ng/m 3 ). The mean intertest coefficient of variation was 8.2%, and the mean intratest variation 4.1 %.
Brugada-Type Electrocardiographic Changes Induced by Fever
Authors: Vishesh Kumar, Neha Patel, Nathan Van Houzen, Neeraj Saini
Journal: Circulation (2013)

A 54-year-old man who was admitted to the hospital with acute cholecystitis developed fever (40°C) and tachycardia.His medical history was significant for hypertension.An ECG revealed sinus tachycardia, incomplete right bundle-branch block, and downsloping (also known as coved-type) ST-segment elevation in leads V 1 and V 2 (Figure 1) with T-wave inversion, consistent with a type 1 Brugada pattern.His cardiac biomarkers were normal, and these ECG changes resolved completely after resolution of the fever with antipyretic agents.The ECGs performed before (Figure 2) and after (Figures 3 and4) the onset of fever induced the Brugada pattern showed incomplete right bundle-branch block without any Brugada-type changes.Because there was no personal or family history of presyncope, syncope, or sudden cardiac arrest, he was managed conservatively.This patient has done well 2 years after discharge.The Brugada ECG pattern is characterized by right bundlebranch block and an elevation at the J point that is >2 mm, with a slowly descending ST-segment in conjunction with flat or negative T waves in leads V 1 , V 2 , and sometimes V 3 . 1These ECG changes are often dynamic and can be unmasked by fever, sodium channel blockers, tricyclic antidepressants, cocaine, and electrolyte abnormalities. 2 Brugada syndrome is diagnosed when these ECG changes are associated with a personal history of syncope, inducible polymorphic ventricular tachycardia, or ventricular fibrillation or a family history of sudden cardiac death.Approximately 25% of cases of Brugada syndrome are caused by mutations in the cardiac sodium channel gene SCN5A.The mutated sodium channels result in temperaturedependent ionic changes that cause characteristic Brugada ECG patterns during fever. 2
Occupational dust exposure and the aetiology of cryptogenic fibrosing alveolitis
Authors: R Hubbard
Journal: European Respiratory Journal (2001)

Cryptogenic fibrosing alveolitis (CFA), synonymous with idiopathic pulmonary fibrosis, is probably a disease entity of increasing frequency. Epidemiological investigations into the aetiology of CFA are at an early age; yet there are several indications that exposures associated with traditionally male manufacturing occupations may be a cause of CFA. Specifically, metal exposure, and to a lesser extent wood dust exposure, was increased in patients with CFA and may explain some cases of CFA. Indeed, the four case-control studies in the literature, to date, have all found an identical occupational exposure to metal or working with metal as a risk factor for CFA and there is now further evidence confirming this association from a case-control study nested within an occupational cohort. There is also evidence from three of the case-control studies that working with wood may be a risk factor for CFA. However, these exposures clearly only explain a minority of cases of cryptogenic fibrosing alveolitis. Further studies amongst different populations with different occupational demographics are required to fully assess the impact of several exposures on the occurrence of cryptogenic fibrosing alveolitis.
Identification of a 60-kD tumor necrosis factor (TNF) receptor as the major signal transducing component in TNF responses.
Authors: B Thoma, M Grell, K Pfizenmaier, P Scheurich
Journal: The Journal of Experimental Medicine (1990)

We describe here a monoclonal antibody (H398) that immunoprecipitates a human 60-kD tumor necrosis factor (TNF) membrane receptor (p60) and competes with TNF binding to p60 but not to p85 TNF receptors. Despite partial inhibition of TNF binding capacity of cells coexpressing both TNF receptor molecules, H398 uniformly and completely inhibits very distinct TNF responses on a variety of cell lines. These data suggest a limited structural heterogeneity in those components actually contributing to TNF responsiveness and identify p60 as a common receptor molecule essential for TNF signal transduction. As H398 is a highly effective TNF antagonist in vitro, it might be useful as a therapeutic agent in the treatment of TNF-mediated acute toxicity.
More Than Baby Steps: Perspectives on Pediatric Translational Research
Authors: Edward Connor, Donald Lombardi, John van den Anker
Journal: Science Translational Medicine (2009)

Although children represent 25% of the U.S. population and nearly 40% of the world's population, pediatric product development typically lags behind that targeted at adults. Here the authors describe the challenges and opportunities of pediatric product development and the unique issues that surround pediatric research. Assuring advancement in pediatric health through clinical and translational medicine is a high priority and an investment in the future.