tbuckley/cabot-search huggingface dataset:
Effect of chronic endogenous hypergastrinaemia on pancreatic growth and carcinogenesis in the hamster.
Authors: M Chu, E Kullman, J F Rehfeld, K Borch
Journal: Gut (1997)

BACKGROUND: To examine the effect of gastrin on spontaneous and induced pancreatic carcinogenesis in the hamster. METHODS AND RESULTS: Two sets of experiments were carried out, one involving long term hypergastrinaemia and one involving cancer induction during hypergastrinaemia. The effect of hypergastrinaemia accomplished by gastric fundectomy was studied for eight months. Neither fundectomised hamsters nor sham operated controls developed premalignant or malignant pancreatic lesions. In the fundectomy group, the mean pancreatic weight, total protein content, and DNA content was increased by 28%, 25%, and 25% respectively. No such increases were found in fundectomised animals receiving a cholecystokinin-B receptor antagonist during the last 24 days of the experiment. In the cancer induction study, the effect of fundectomy on N-nitrosobis(2-oxopropyl) amine induced pancreatic carcinogenesis was studied for three months. There were no significant differences in the incidence or [3H]-thymidine labelling index of focal pancreatic lesions between fundectomised and sham operated control animals. CONCLUSIONS: Fundectomy with chronic hypergastrinaemia induces pancreatic hypertrophy, but does not enhance N-nitrosobis (2-oxopropyl)amine induced pancreatic carcinogenesis in the hamster. The increases in growth were inhibited by a cholecystokinin-B receptor antagonist, indicating that the trophic effect of fundectomy is mediated by gastrin.
Metabolomic signatures in nuclear magnetic resonance spectra of exhaled breath condensate identify asthma
Authors: A. Sinha, V. Krishnan, T. Sethi, S. Roy, B. Ghosh, R. Lodha, S. Kabra, A. Agrawal
Journal: European Respiratory Journal (2012)

To the Editors:

Exhaled breath condensate (EBC) holds promise as a noninvasive method of collecting airway-lining fluid, although at an unknown dilution [1]. While metabolomic studies of EBC using nuclear magnetic resonance (NMR) spectroscopy have previously shown promise in asthma diagnosis and subtyping [2, 3], a study that was recently published in the European Respiratory Journal that failed to find usable NMR signature in EBC collections from disposable systems [4]. This led the authors to conclude that NMR metabolomics lacks sufficient sensitivity for metabolic fingerprinting of EBC. Interestingly, they were able to obtain high quality results from the same samples with mass spectroscopy, which they recommended for future use. As this is a nascent and technically complex field, we present our very different early experiences, which suggest that reproducible, valid and useful NMR metabolomic fingerprinting of EBC is indeed possible. Specifically, we found that the presence or absence of a trident peak at 7 ppm during NMR spectroscopy reliably distinguished between EBC samples collected from normal and asthmatic subjects, respectively. This peak probably represents ammonium ion, loss of which in asthma is consistent with reduced expression of glutaminase, an enzyme that converts glutamine to glutamate and ammonia [5].

Institutional committees approved all research protocols. The subjects included both adults (>21 yrs) and children (6–15 yrs). Adult asthmatic subjects (n=7) were physician diagnosed, meeting American Thoracic Society/European Respiratory Society criteria [6], and were nonsmokers. Control normal adults were healthy nonsmoking volunteers (n=10). The children were part of an ongoing prospective asthma cohort for which multidimensional genotype and phenotype data is being …
Negative selection of CD4+CD8+ thymocytes by T cell receptor-induced apoptosis requires a costimulatory signal that can be provided by CD28.
Authors: J A Punt, B A Osborne, Y Takahama, S O Sharrow, A Singer
Journal: The Journal of Experimental Medicine (1994)

CD4+CD8+ thymocytes expressing self-reactive T cell antigen receptors (TCR) are deleted in the thymus as a consequence of TCR/self-antigen/major histocompatibility complex interactions. However, the signals that are necessary to initiate clonal deletion have not yet been clarified. Here we demonstrate that TCR engagement does not efficiently induce apoptosis of CD4+CD8+ thymocytes, although it generates signals that increase expression of CD5, a thymocyte differentiation marker. In fact, TCR signals fail to induce thymocyte apoptosis even when augmented by simultaneous engagement with CD4 or lymphocyte function 1-associated molecules. In marked contrast, signals generated by engagement of both TCR and the costimulatory molecule CD28 potently induce apoptosis of CD4+CD8+ thymocytes. Thus, the present results define a requirement for both TCR and costimulatory signals for thymocyte apoptosis and identify CD28 as one molecule that is capable of providing the necessary costimulus. These results provide a molecular basis for differences among cell types in their ability to mediate negative selection of developing thymocytes.
Peripartum Management of Glycemia in Women With Type 1 Diabetes
Authors: Naomi Achong, Emma L. Duncan, H. David McIntyre, Leonie Callaway
Journal: Diabetes Care (2013)

We aimed to 1) describe the peripartum management of type 1 diabetes at an Australian teaching hospital and 2) discuss factors influencing the apparent transient insulin independence postpartum.We conducted a retrospective review of women with type 1 diabetes delivering singleton pregnancies from 2005 to 2010. Information was collected regarding demographics, medical history, peripartum management and outcome, and breast-feeding. To detect a difference in time to first postpartum blood glucose level (BGL) >8 mmol/L between women with an early (<4 h) and late (>12 h) requirement for insulin postpartum, with a power of 80% and a type 1 error of 0.05, at least 24 patients were required.An intravenous insulin infusion was commenced in almost 95% of women. Univariate analysis showed that increased BMI at term, lower creatinine at term, longer duration from last dose of long- or intermediate-acting insulin, and discontinuation of an insulin infusion postpartum were associated with a shorter time to first requirement of insulin postpartum (P = 0.005, 0.026, 0.026, and <0.001, respectively). There was a correlation between higher doses of insulin commenced postpartum and number of out-of-range BGLs (r[36] = 0.358, P = 0.030) and hypoglycemia (r[36] = 0.434, P = 0.007). Almost 60% had at least one BGL <3.5 mmol/L between delivery and discharge.Changes in the pharmacodynamic profile of insulin may contribute to the transient insulin independence sometimes observed postpartum in type 1 diabetes. A dose of 50-60% of the prepregnancy insulin requirement resulted in the lowest rate of hypoglycemia and glucose excursions. These results require validation in a larger, prospective study.
Left Ventricular Mass and Ventricular Remodeling Among Hispanic Subgroups Compared With Non-Hispanic Blacks and Whites
Authors: Carlos J. Rodriguez, Ana V. Diez-Roux, Andrew Moran, Zhezhen Jin, Richard A. Kronmal, Joao Lima, Shunichi Homma, David A. Bluemke, R. Graham Barr
Journal: Journal of the American College of Cardiology (2010)
Effect of Chronic Metabolic Acidosis on Calbindin Expression along the Rat Distal Tubule
Authors: MARIA RIZZO, GIOVAMBATTISTA CAPASSO, MARKUS BLEICH, ANGELO PICA, DOMENICO GRIMALDI, RENÉ J. M. BINDELS, RAINER GREGER
Journal: Journal of the American Society of Nephrology (2000)

Calbindin D28k has been reported to be involved in the transcellular calcium transport along the rat distal tubule. It has also been shown that chronic metabolic acidosis (CMA) induces significant hypercalciuria. The present study investigated whether CMA affects the mRNA and the protein expression of calbindin D28k along isolated distal tubule (DT) of rats. The animals were made acidotic by adding 0.28 mol/L NH4Cl to the drinking water for 7 d. This maneuver was associated with an increase in plasma ionized calcium. Inulin clearance experiments demonstrated that metabolic acidosis did not affect GFR, but it significantly increased both total and fractional urinary calcium excretion. To define the role of calbindin D28k, total RNA was extracted from DT, identified, and microdissected from collagenase-treated kidneys. cDNA was synthesized from RNA using reverse transcriptase and oligo(dT)12-18 primers. Calbindin D28k mRNA abundance was semiquantified by a competitive reverse transcription-PCR, using an internal standard of cDNA that differed from the wild-type calbindin D28k by a deletion of 86 bp. The reverse transcription-PCR was performed starting from the same amount of total RNA. For each set of experiments, control and acidotic rats were studied in parallel. The identity of the DT was further verified by the presence of the thiazide-sensitive NaCl cotransporter (rTSC1) mRNA. Calbindin D28k mRNA abundance was 0.89 ± 0.21 amol/ng total RNA in DT of CMA rats (n = 5) compared with 0.30 ± 0.12 amol/ng total RNA of control rats (n = 5) (P < 0.05). Using specific rabbit polyclonal anti-calbindin D28k antibody, Western blotting was performed starting from thin slices of outer cortex. Densitometric analysis revealed that in acidotic rats (n = 7) there was a 17 ± 5% (P < 0.05) increase in calbindin D28k protein abundance compared with controls (n = 7). These results indicate that in the rat, ammonium chloride loading induces an increase in filtered ionized calcium load that is associated with a significant upregulation of calbindin D28k both at the mRNA and protein level. These last effects will help to reduce the concomitant hypercalciuria, thus mitigating the consequence of CMA on calcium metabolism.
Relative Failure of Saturated Fat in the Diet to Produce Atherosclerosis in the Rabbit
Authors: WILLIAM E. CONNOR, JAY J. ROHWEDDER, MARK L. ARMSTRONG
Journal: Circulation Research (1967)

Three "saturated" fats of vegetable origin were fed to different groups of rabbits for periods up to 1 year. Cocoa butter and a hydrogenated vegetable oil shortening produced no hypercholesterolemia. Coconut oil feeding increased the serum cholesterol concentrations for 4 months, but a decline to baseline values occurred after 6 months. No gross atherosclerosis occurred in any animal fed coconut oil or the hydrogenated vegetable oil shortening. Slight atherosclerotic lesions were found in 50% of the rabbits fed cocoa butter. Aortic cholesterol content was slightly increased in animals fed coconut oil and cocoa butter. Dietary fats, even when highly saturated, had only a minimal capacity to produce atherosclerosis in the rabbit, a species usually highly susceptible to the induction of atherosclerosis. When a moderate amount of cholesterol was added to the diet, the serum cholesterol levels increased greatly and considerable atherosclerosis resulted.
Revised Response Criteria for Malignant Lymphoma
Authors: Bruce D. Cheson, Beate Pfistner, Malik E. Juweid, Randy D. Gascoyne, Lena Specht, Sandra J. Horning, Bertrand Coiffier, Richard I. Fisher, Anton Hagenbeek, Emanuele Zucca, Steven T. Rosen, Sigrid Stroobants, T. Andrew Lister, Richard T. Hoppe, Martin Dreyling, Kensei Tobinai, Julie M. Vose, Joseph M. Connors, Massimo Federico, Volker Diehl
Journal: Journal of Clinical Oncology (2007)

Purpose Standardized response criteria are needed to interpret and compare clinical trials and for approval of new therapeutic agents by regulatory agencies. Methods The International Working Group response criteria (Cheson et al, J Clin Oncol 17:1244, 1999) were widely adopted, but required reassessment because of identified limitations and the increased use of [ 18 F]fluorodeoxyglucose-positron emission tomography (PET), immunohistochemistry (IHC), and flow cytometry. The International Harmonization Project was convened to provide updated recommendations. Results New guidelines are presented incorporating PET, IHC, and flow cytometry for definitions of response in non-Hodgkin's and Hodgkin's lymphoma. Standardized definitions of end points are provided. Conclusion We hope that these guidelines will be adopted widely by study groups, pharmaceutical and biotechnology companies, and regulatory agencies to facilitate the development of new and more effective therapies to improve the outcome of patients with lymphoma.
Isolated dislocation of the proximal tibiofibular joint in a long jumper
Authors: A J Laing, B Lenehan, A Ali, C V R Prasad
Journal: British Journal of Sports Medicine (2003)

Acute traumatic proximal tibiofibular joint dislocation is an exceedingly rare injury. This is a case report in a rare horizontal type joint variant, following a long jump injury. The diagnostic approach when this injury is suspected is described.
Redox Signaling in Cardiac Physiology and Pathology
Authors: Joseph R. Burgoyne, Héloïse Mongue-Din, Philip Eaton, Ajay M. Shah
Journal: Circulation Research (2012)

Redox signaling refers to the specific and usually reversible oxidation/reduction modification of molecules involved in cellular signaling pathways. In the heart, redox signaling regulates several physiological processes (eg, excitation-contraction coupling) and is involved in a wide variety of pathophysiological and homoeostatic or stress response pathways. Reactive oxygen species involved in cardiac redox signaling may derive from many sources, but NADPH oxidases, as dedicated sources of signaling reactive oxygen species, seem to be especially important. An increasing number of specific posttranslational oxidative modifications involved in cardiac redox signaling are being defined, along with the reactive oxygen species sources that are involved. Here, we review current knowledge on the molecular targets of signaling reactive oxygen species in cardiac cells and their involvement in cardiac physiopathology. Advances in this field may allow the development of targeted therapeutic strategies for conditions such as heart failure as opposed to the general antioxidant approaches that have failed to date.
Impacts of the 3/11 Disaster in Fukushima on Asthma Control
Authors: Atsuro Fukuhara, Suguru Sato, Manabu Uematsu, Kenichi Misa, Takefumi Nikaido, Yayoi Inokoshi, Naoko Fukuhara, Xintao Wang, Kenya Kanazawa, Yoshinori Tanino, Takashi Ishida, Mitsuru Munakata
Journal: American Journal of Respiratory and Critical Care Medicine (2012)
The Global Cardiovascular Risk Transition
Authors: Goodarz Danaei, Gitanjali M. Singh, Christopher J. Paciorek, John K. Lin, Melanie J. Cowan, Mariel M. Finucane, Farshad Farzadfar, Gretchen A. Stevens, Leanne M. Riley, Yuan Lu, Mayuree Rao, Majid Ezzati
Journal: Circulation (2013)

Background— It is commonly assumed that cardiovascular disease risk factors are associated with affluence and Westernization. We investigated the associations of body mass index (BMI), fasting plasma glucose, systolic blood pressure, and serum total cholesterol with national income, Western diet, and, for BMI, urbanization in 1980 and 2008. Methods and Results— Country-level risk factor estimates for 199 countries between 1980 and 2008 were from a previous systematic analysis of population-based data. We analyzed the associations between risk factors and per capita national income, a measure of Western diet, and, for BMI, the percentage of the population living in urban areas. In 1980, there was a positive association between national income and population mean BMI, systolic blood pressure, and total cholesterol. By 2008, the slope of the association between national income and systolic blood pressure became negative for women and zero for men. Total cholesterol was associated with national income and Western diet in both 1980 and 2008. In 1980, BMI rose with national income and then flattened at ≈Int$7000; by 2008, the relationship resembled an inverted U for women, peaking at middle-income levels. BMI had a positive relationship with the percentage of urban population in both 1980 and 2008. Fasting plasma glucose had weaker associations with these country macro characteristics, but it was positively associated with BMI. Conclusions— The changing associations of metabolic risk factors with macroeconomic variables indicate that there will be a global pandemic of hyperglycemia and diabetes mellitus, together with high blood pressure in low-income countries, unless effective lifestyle and pharmacological interventions are implemented.
Pesticide Use Modifies the Association Between Genetic Variants on Chromosome 8q24 and Prostate Cancer
Authors: Stella Koutros, Laura E. Beane Freeman, Sonja I. Berndt, Gabriella Andreotti, Jay H. Lubin, Dale P. Sandler, Jane A. Hoppin, Kai Yu, Qizhai Li, Laura A. Burdette, Jeffrey Yuenger, Meredith Yeager, Michael C.R. Alavanja
Journal: Cancer Research (2010)

Genome-wide association studies have identified 8q24 region variants as risk factors for prostate cancer. In the Agricultural Health Study, a prospective study of licensed pesticide applicators, we observed increased prostate cancer risk with specific pesticide use among those with a family history of prostate cancer. Thus, we evaluated the interaction among pesticide use, 8q24 variants, and prostate cancer risk. The authors estimated odds ratios (OR) and 95% confidence intervals (95% CI) for interactions among 211 8q24 variants, 49 pesticides, and prostate cancer risk in 776 cases and 1,444 controls. The ORs for a previously identified variant, rs4242382, and prostate cancer increased significantly (P<0.05) with exposure to the organophosphate insecticide fonofos, after correction for multiple testing, with per allele ORnonexposed of 1.17 (95% CI, 0.93-1.48), per allele OR(low) of 1.30 (95% CI, 0.75-2.27), and per allele ORhigh of 4.46 (95% CI, 2.17-9.17; P-interaction=0.002, adjusted P-interaction=0.02). A similar effect modification was observed for three other organophosphate insecticides (coumaphos, terbufos, and phorate) and one pyrethroid insecticide (permethrin). Among ever users of fonofos, subjects with three or four risk alleles at rs7837328 and rs4242382 had approximately three times the risk of prostate cancer (OR, 3.14; 95% CI, 1.41-7.00) compared with subjects who had zero risk alleles and never used fonofos. We observed a significant interaction among variants on chromosome 8q24, pesticide use, and risk of prostate cancer. Insecticides, particularly organophosphates, were the strongest modifiers of risk, although the biological mechanism is unclear. This is the first report of effect modification between 8q24 and an environmental exposure on prostate cancer risk.
The COST study: a multicenter trial comparing measurements of cardiac output by thoracic electrical bioimpedance with thermodilution
Authors: A. Raisinghani, N.V. Diaco, S.W. Sageman, B.D. Spless, B.R. Williams, P. Belott, K. Ohmori, A.N. DeMaria
Journal: Journal of the American College of Cardiology (1998)
Evolutionarily Conserved Promoter Region Containing CArG*-Like Elements Is Crucial for Smooth Muscle Myosin Heavy Chain Gene Expression
Authors: A. Zilberman, V. Dave, J. Miano, E. N. Olson, M. Periasamy
Journal: Circulation Research (1998)

Abstract —In recent years, significant progress has been made toward understanding skeletal muscle development. However, the mechanisms that regulate smooth muscle development and differentiation are presently unknown. To better understand smooth muscle–specific gene expression, we have focused our studies on the smooth muscle myosin heavy chain (SMHC) gene, a highly specific marker of differentiated smooth muscle cells. The goal of the present study was to isolate and characterize the mouse SMHC gene promoter, since the mouse promoter would be particularly suited for in vivo promoter analyses in transgenic mice and would serve as a tool for targeting genes of interest into smooth muscle cells. We report here the isolation and characterization of the mouse SMHC promoter and its 5′ flanking region. DNA sequence analysis of a 2.6-kb portion of the promoter identified several potential binding sites for known transcription factors. Transient transfection analysis of promoter deletion constructs in primary cultures of smooth muscle cells showed that the region between −1208 and −1050 bp is critical for maximal SMHC promoter activity. A comparison of SMHC promoter sequences from mouse, rat, and rabbit revealed the presence of a highly conserved region located between −967 and −1208 bp. This region includes three CArG/CArG*-like elements, two SP-1 binding sites, a NF-1–like element, an Nkx2–5 binding site, and an Elk-1 binding site. Gel mobility shift assay and DNase I footprinting analyses show that all three CArG/CArG*-like elements can form DNA-protein complexes with nuclear extract from vascular smooth muscle cells. Protein binding to the CArG* elements can be competed out by either serum response element or by an authentic CArG element from the cardiac α-actin gene. Using a serum response factor (SRF) antibody, we demonstrate that SRF is part of the protein complex. In addition, we show that cotransfection with the SRF dominant-negative mutant expression vector abolishes SMHC promoter activity, suggesting that SRF protein plays a critical role in SMHC gene regulation.
Nodular pseudotumoral pulmonary amyloidosis mimicking pulmonary carcinoma
Authors: M Pusztaszeri
Journal: Thorax (2005)

A 72 year old woman was admitted for a cholecystectomy. The preoperative chest radiograph revealed an incidental pulmonary density in the left upper lobe. Her medical history was non-contributory. She was a non-smoker and had neither pulmonary nor systemic symptoms. A CT scan showed a 5 cm diameter non-calcified mass in the left upper lobe (fig 1A). Mediastinal lymphadenopathy was not present. Positron emission tomography with 18F-FDG (FDG-PET) showed that the …
Diagnostic Accuracy and Clinical Utility of Noninvasive Testing for Coronary Artery Disease
Authors: Annick C. Weustink
Journal: Annals of Internal Medicine (2010)

Background: Computed tomography coronary angiography (CTCA) has become a popular noninvasive test for diagnosing coronary artery disease. Objective: To compare the accuracy and clinical utility of stress testing and CTCA for identifying patients who require invasive coronary angiography (ICA). Design: Observational study. Setting: University medical center in Rotterdam, the Netherlands. Patients: 517 patients referred by their treating physicians for evaluation of chest symptoms by using stress testing or ICA. Intervention: Stress testing and CTCA in all patients. Measurements: Diagnostic accuracy of stress testing and CTCA compared with ICA; pretest probabilities of disease by Duke clinical score; and clinical utility of noninvasive testing, defined as a pretest or posttest probability that suggests how to proceed with testing (no further testing if ≤5%, proceed with ICA if between 5% and 90%, and refer directly for ICA if ≥90%). Results: Stress testing was not as accurate as CTCA; CTCA sensitivity approached 100%. In patients with a low (<20%) pretest probability of disease, negative stress test or CTCA results suggested no need for ICA. In patients with an intermediate (20% to 80%) pretest probability, a positive CTCA result suggested need to proceed with ICA (posttest probability, 93% [95% CI, 92% to 93%]) and a negative result suggested no need for further testing (posttest probability, 1% [CI, 1% to 1%]). Physicians could proceed directly with ICA in patients with a high (>80%) pretest probability (91% [CI, 90% to 92%]). Limitations: Referral and verification bias might have influenced findings. Stress testing provides functional information that may add value to that from anatomical (CTCA or ICA) imaging. Conclusion: Computed tomography coronary angiography seems most valuable in patients with intermediate pretest probability of disease, because the test can distinguish which of these patients need invasive angiography. These findings need to be confirmed before CTCA can be routinely recommended for these patients. Primary Funding Source: None.