tbuckley/cabot-search huggingface dataset:
Estimation of activity apoptosis genes based on expression of Bcl2, Bax, caspase-3 activity in bronchial epithelium in asthma
Authors: Valeriy Mineev, Irina Nesterovich, Vasiliy Trofimov, Tatiana Kashintseva, Alexandra Miroshkina, Margarita Rybakova, Roman Grozov, Vadim Baikov
Journal: European Respiratory Journal (2012)

Aim : The aim is to reveal the disorders of apoptosis in bronchial epithelium in bronchial asthma (BA) based on the estimation of expression of Bcl2, Bax, caspase-3.   Methods : In 21 patients a fibreoptic bronchoscopy was performed (patients have signed the ICF). Expression of Bcl2, Bax, CPP32 (caspase-3 activity) in bronchial epithelium was performed by immunohistochemical analysis of bronchus biopsies taken in fibrobronchoscopy using DAKO kits.   Results : In allergic BA elevation of Bcl2 expression and decrease of Bax expression compared to nonallergic BA and oral glucocorticoids taking patients were found. Activity of Bax expression was significant decreased in allergic BA compared to that in other groups. The same data were revealed on analysis of Bcl-2/Bax index. Expression level of caspase-3 was high in both groups.   Conclusion : Features of apoptosis in bronchial epithelium in different variants of BA could indicate to different pathogenetic mechanisms of apoptosis in allergic inflammation persistence.
The Endocrine Society Meeting: Topics in Insulin Sensitivity and Hypertension
Authors: Zachary T. Bloomgarden
Journal: Diabetes Care (2003)

Lectures at the Endocrine Society’s 85th Annual Meeting in Philadelphia, Pennsylvania, 19–22 June 2003, showed the fascinating interplay of basic science and clinical medicine needed to appreciate our advancing knowledge of diabetes.

A series of new intracellular signaling pathways related to insulin action are being identified. John C. Lawrence (Charlottesville, VA) discussed the mTOR pathway. The immunosuppressant rapamycin inhibits cell growth by interfering with the function of a kinase, termed mammalian target of rapamycin (mTOR). mTOR is defined by high affinity binding to rapamycin, regulating various steps in carbohydrate, lipid, and protein metabolism, particularly the protein kinases eukaryotic initiation factor 4E binding protein 1 (4E-BP1) and the 40S ribosomal protein S6 kinase (p70s6k), which is involved in protein synthesis. mTOR is present in adipocytes and induced during adipogenesis. mTOR is regulated by an amino acid nutrient-sensing pathway that is particularly stimulated by branched chain amino acids such as leucine and growth factors such as insulin via protein kinase B (PKB), with a potential feedback loop whereby mTOR increases serine phosphorylation of insulin receptor substrate-1 and -2. Both insulin and PKB increase the phosphorylation of mTOR via another protein, mTOR kinase. 4E-BP1 is another protein with multiple phosphorylation sites affected by insulin; in particular, there are three threonine sites that are all affected by rapamycin. Lawrence concluded that mTOR, in combination with a series of other proteins, one with the intriguing name Raptor because of an effect of rapamycin that causes it to dissociate from the complex, binds and phosphorylates substrates such as 4E-BP1.

Gustav E Lienhard (Hanover, NH) addressed the question of the signal transduction pathway from the insulin receptor leading to GLUT4 translocation to the plasma membrane, mediating glucose transport. Insulin activates phosphoinositide 3-kinase, leading in turn to activation of a serine kinase originally identified as a proto-oncogene …
Direct Preconditioning of Cardiac Myocytes via Opioid Receptors and K <sub>ATP</sub> Channels
Authors: Bruce T. Liang, Garrett J. Gross
Journal: Circulation Research (1999)

Abstract —Previous studies demonstrated that opioid receptor activation mimics the cardioprotective effect of ischemic preconditioning via K ATP channels in the intact heart. However, it is unknown whether this beneficial effect is exerted at the level of the cardiac myocyte or coronary vasculature or is mediated via the sarcolemmal or the mitochondrial K ATP channel. Thus, the purpose of the present study was to investigate whether opioid receptor stimulation could mimic the cardioprotective effect of preconditioning in a cardiac myocyte model of simulated ischemia. Cardiac ventricular myocytes cultured from chick embryos 14 days in ovo were used as an in vitro model for ischemic preconditioning. A 5-minute exposure of the myocytes to the opioid receptor agonist morphine protected the myocytes during a subsequent 90-minute period of simulated ischemia, which was manifested as a pronounced reduction in the percentage of cardiac cells killed and the amount of creatine kinase released during ischemia. The preconditioning-like effect of morphine was concentration-dependent, reached a maximal effect at 1 μmol/L, and was reversed by naloxone (0.1 to 10 μmol/L). When K ATP channel antagonists, such as glibenclamide, or the mitochondrial selective inhibitor 5-hydroxydecanoic acid were present during preexposure to morphine, they abolished the protective effect of morphine. Thus, cardiac myocytes express functional opioid receptors, and their activation mimics the cardioprotective effect of ischemic preconditioning. These results provide direct evidence that the preconditioning-like effect of morphine in the intact heart can be exerted at the level of cardiac myocytes and is most likely the result of mitochondrial K ATP channel activation.
Obesity increases oesophageal acid exposure
Authors: H. B El-Serag, G. A Ergun, J. Pandolfino, S. Fitzgerald, T. Tran, J. R Kramer
Journal: Gut (2006)

Obesity has been associated with gastro-oesophageal reflux disease (GERD); however, the mechanism by which obesity may cause GERD is unclear.To examine the association between oesophageal acid exposure and total body or abdominal anthropometric measures.A cross-sectional study of consecutive patients undergoing 24 h pH-metry was conducted. Standardised measurements of body weight and height as well as waist and hip circumference were obtained. The association between several parameters of oesophageal acid exposures and anthropometric measures were examined in univariate and multivariate analyses.206 patients (63% women) with a mean age of 51.4 years who were not on acid-suppressing drugs were enrolled. A body mass index (BMI) of >30 kg/m(2) (compared with BMI<25 kg/m(2)) was associated with a significant increase in acid reflux episodes, long reflux episodes (>5 min), time with pH<4, and a calculated summary score. These significant associations have affected total, postprandial, upright and supine pH measurements. Waist circumference was also associated with oesophageal acid exposure, but was not as significant or consistent as BMI. When adjusted for waist circumference by including it in the same model, the association between BMI>30 kg/m(2) and measures of oesophageal acid exposure became attenuated for all, and not significant for some, thus indicating that waist circumference may mediate a large part of the effect of obesity on oesophageal acid exposure.Obesity increases the risk of GERD, at least partly, by increasing oesophageal acid exposure. Waist circumference partly explains the association between obesity and oesophageal acid exposure.
IL-36γ Transforms the Tumor Microenvironment and Promotes Type 1 Lymphocyte-Mediated Antitumor Immune Responses
Authors: Xuefeng Wang, Xin Zhao, Chao Feng, Aliyah Weinstein, Rui Xia, Wen Wen, Quansheng Lv, Shuting Zuo, Peijun Tang, Xi Yang, Xiaojuan Chen, Hongrui Wang, Shayang Zang, Lindsay Stollings, Timothy L. Denning, Jingting Jiang, Jie Fan, Guangbo Zhang, Xueguang Zhang, Yibei Zhu, Walter Storkus, Binfeng Lu
Journal: Cancer Cell (2015)
Nasal biopsy is superior to nasal smear for finding eosinophils in nonallergic rhinitis
Authors: K. Ingels, J.‐P. Durdurez, C. Cuvelier, P. van Cauwenberge
Journal: Allergy (1997)

The presence of eosinophils was compared in nasal biopsy and smear. Thirty‐two nonallergic rhinitis patients, of whom six had nasal polyps, were included in the study. The specimens were studied light‐microscopically after staining with hematoxylin‐eosin. The association between the presence of polyps and the finding of eosinophils in the biopsy specimens proved to be significant. Ten normal subjects served as controls. It was far more simple to detect eosinophils in the biopsy samples than in the nasal smears. When we considered biopsies with at least four eosinophils in four fields as hypereosinophilic, our group of patients contained 25% nonallergic rhinitis with eosinophilia syndrome (NARES) patients.
Decrease in Coronary Blood Flow Reserve During Hyperlipidemia Is Secondary to an Increase in Blood Viscosity
Authors: Se-Joong Rim, Howard Leong-Poi, Jonathan R. Lindner, Kevin Wei, Nicholas G. Fisher, Sanjiv Kaul
Journal: Circulation (2001)

During maximal hyperemia, capillaries provide the greatest resistance to flow. A major determinant of capillary resistance is viscosity. We, therefore, hypothesized that abnormal coronary blood flow (CBF) reserve observed during hyperlipidemia is secondary to increased blood viscosity and not abnormal coronary vasomotion.Maximal hyperemia was induced in 9 dogs using adenosine. Serum triglyceride levels were increased by incremental doses of Intralipid. A good correlation was noted between serum triglyceride levels and blood viscosity (r=0.82). Neither total coronary blood volume nor myocardial blood volume changed with increasing serum triglyceride levels, indicating lack of vasomotion. Myocardial vascular resistance (MVR) increased with increasing triglyceride levels (r=0.84), while hyperemic myocardial blood flow (MBF) decreased (r=-0.64). The decrease in hyperemic MBF was associated with a decrease in blood velocity (r=-0.56). These findings were confirmed with direct intravital microscopic observations in the mice cremaster muscle.Increasing lipid levels in a fully dilated normal coronary bed causes no change in large or small vessel dimensions. Instead, the increase in blood viscosity causes capillary resistance to rise, which attenuates hyperemic CBF. Therefore, the abnormal CBF reserve associated with hyperlipidemia is due to increase blood viscosity and not abnormal vascular function.
Pharmacogenetics, Drug-Metabolizing Enzymes, and Clinical Practice
Authors: Sharon J. Gardiner, Evan J. Begg
Journal: Pharmacological Reviews (2006)

The application of pharmacogenetics holds great promise for individualized therapy. However, it has little clinical reality at present, despite many claims. The main problem is that the evidence base supporting genetic testing before therapy is weak. The pharmacology of the drugs subject to inherited variability in metabolism is often complex. Few have simple or single pathways of elimination. Some have active metabolites or enantiomers with different activities and pathways of elimination. Drug dosing is likely to be influenced only if the aggregate molar activity of all active moieties at the site of action is predictably affected by genotype or phenotype. Variation in drug concentration must be significant enough to provide "signal" over and above normal variation, and there must be a genuine concentration-effect relationship. The therapeutic index of the drug will also influence test utility. After considering all of these factors, the benefits of prospective testing need to be weighed against the costs and against other endpoints of effect. It is not surprising that few drugs satisfy these requirements. Drugs (and enzymes) for which there is a reasonable evidence base supporting genotyping or phenotyping include suxamethonium/mivacurium (butyrylcholinesterase), and azathioprine/6-mercaptopurine (thiopurine methyltransferase). Drugs for which there is a potential case for prospective testing include warfarin (CYP2C9), perhexiline (CYP2D6), and perhaps the proton pump inhibitors (CYP2C19). No other drugs have an evidence base that is sufficient to justify prospective testing at present, although some warrant further evaluation. In this review we summarize the current evidence base for pharmacogenetics in relation to drug-metabolizing enzymes.
Characterization of oscillations in ventricular refractoriness in man after an abrupt increment in heart rate.
Authors: F E Marchlinski
Journal: Circulation (1987)

Oscillations in ventricular myocardial refractoriness after a change in rate have not been described in man. During 25 baseline paced cycle lengths (SB-SB) of 400 to 800 msec in 14 patients, a shorter cycle length (S'-S') was introduced that was 10 to 20 msec (mean 15 +/- 5) greater in duration than the ventricular effective refractory period (VERP) determined after 12 beats of the respective baseline cycle length (group 1 trials). In addition, during 14 of the 25 baseline cycle lengths, a second shorter cycle length was introduced that was 50 to 80 msec (mean 65 +/- 10) greater than the VERP of the respective baseline cycle length (group 2 trials). In all 39 group 1 and group 2 trials the VERP was determined after each of at least 3 beats (S'1, S'2, S'3) of the shorter cycle length and in six of the 25 group I trials the VERP was determined after each of at least 12 beats of the shorter cycle length. In all group 1 trials oscillations of the VERP were observed, with a mean S'1 VERP of 202 +/- 28 msec, an S'2 VERP of 228 +/- 25 msec (p less than .001 vs S'1 VERP), and an S'3 VERP of 210 +/- 26 msec (p less than .001 vs S'2 VERP). Oscillations dampened within 4 beats, but persisted at a lower amplitude in four of the six group I trials during which the shorter cycle length was maintained for at least 12 beats.(ABSTRACT TRUNCATED AT 250 WORDS)
The Autonomic Nervous System in Congestive Heart Failure
Authors: G S Francis, J N Cohn
Journal: Annual Review of Medicine (1986)

Congestive heart failure is a complex clinical syndrome characterized by striking abnormalities of the autonomic nervous system. The mechanisms and biological importance of these disturbances are not clearly defined. Nonetheless, it is possible that autonomic disturbances play an important role in the pathophysiology and prognosis of heart failure, and therefore drugs that alter autonomic function may provide additional therapeutic options in the management of this syndrome.
Nontuberculous mycobacteria. An underappreciated cause of geriatric lung disease.
Authors: T P Kennedy, D J Weber
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Nontuberculous mycobacteria (NTM) infection is a frequent opportunistic infection in patients infected with the human immunodeficiency virus. However, NTM infection may also occur in nonimmunocompromised hosts. In order to determine the spectrum of mycobacterial infection in the nonacademic setting, we analyzed the demographic and clinical characteristics of all patients presenting to a suburban multispecialty clinic during a 24-mo period. Twenty-one patients presented with active mycobacterial lung infections during the study period. Of these, only one had Mycobacterium tuberculosis. The remaining 20 had lung infections with NTM. One patient was infected with M. kansasii, three had M. abscessus, and 16 had M. avium complex. One patient with disseminated M. avium infection met the diagnostic criteria for the acquired immunodeficiency syndrome. The remaining 19 were largely normal at presentation and were predominantly elderly (mean age, 71 +/- 11 yr), female (79%), nonsmokers (89%) who presented with cough (94%) and localized radiographic infiltrates (84%), often in the right middle lobe and/or lingula (73%). The predominance of nontuberculous mycobacteria over M. tuberculosis in our practice was mirrored by results of an 11-yr review of experience from a nearby suburban hospital, where 65% of mycobacterial infections in the previous 5 yr were with NTM. We conclude that infection with NTM represents a previously underappreciated cause of chronic lung infection among elderly middle-class patients in the community setting.
Heart failure risk among patients with rheumatoid arthritis starting a TNF antagonist
Authors: Daniel H Solomon, Jeremy A Rassen, Bindee Kuriya, Lang Chen, Leslie R Harrold, David J Graham, James D Lewis, Joyce Lii, Liyan Liu, Marie R Griffin, J R Curtis
Journal: Annals of the Rheumatic Diseases (2012)

Heaf testing was carried out on 98 preschool Asian children who had received a BCG vaccination. A strongly positive Heaf reaction (grade 3) occurred in only two children. Heaf testing can still be used in tuberculosis screening after neonatal BCG.
Chronic stable asthma and the normal arterial pressure of carbon dioxide in hypoxia.
Authors: G M Cochrane, J G Prior, C B Wolff
Journal: BMJ (1980)

Arterial blood-gas tensions, pH, and peak expiratory flow rate were measured in 29 patients with chronic asthma in a stable state. The hypoxia in these patients was found to be comparable with the hypoxia seen in normal subjects at high altitude in its effects on arterial pressure of carbon dioxide (PaCO2). These results suggest that in patients with asthma the PaCO2 taken as normal should be related to the arterial oxygen tension. Any increase in the observed value compared with this predicted value indicates impaired respiratory control. This may well help in assessing the patients at greatest risk during an attack of asthma.
Chlorhexidine Compared with Povidone-Iodine as Skin Preparation before Blood Culture
Authors: Olivier Mimoz, Amal Karim, Alain Mercat, Marie Cosseron, Bruno Falissard, Fabrice Parker, Christian Richard, Kamran Samii, Patrice Nordmann
Journal: Annals of Internal Medicine (1999)

Background: Chlorhexidine is better than povidone-iodine for care of catheter sites, but it is not known whether chlorhexidine is superior in reducing blood culture contamination. Objective: To determine whether alcoholic chlorhexidine is a more effective skin antiseptic for collection of blood cultures than aqueous povidone-iodine. Design: Randomized, controlled trial. Setting: Three adult intensive care units in a French university hospital. Patients: 403 adults who had at least one blood culture drawn through a peripheral vein. Interventions: Patients were randomly assigned to receive skin preparation with an aqueous solution of 10% povidone-iodine or an alcoholic solution of 0.5% chlorhexidine before phlebotomy. Measurements: Contamination rates of blood cultures. Results: Of 2041 blood cultures collected in 403 patients, 124 yielded pathogens. Chlorhexidine reduced the incidence of blood culture contamination more than povidone-iodine (14 of 1019 cultures [1.4%] compared with 34 of 1022 cultures [3.3%]; odds ratio, 0.40 [95% CI, 0.21 to 0.75]; P = 0.004). Conclusion: Skin preparation with alcoholic chlorhexidine is more efficacious than skin preparation with aqueous povidone-iodine in reducing contamination of blood cultures.
Serious and Life-Threatening Pregnancy-Related Infections: Opportunities to Reduce the Global Burden
Authors: Courtney A. Gravett, Michael G. Gravett, Emily T. Martin, Jeffrey D. Bernson, Sadaf Khan, David S. Boyle, Sophia M. R. Lannon, Janna Patterson, Craig E. Rubens, Matthew S. Steele
Journal: PLoS Medicine (2012)

Michael Gravett and colleagues review the burden of pregnancy-related infections, especially in low- and middle-income countries, and offer suggestions for a more effective intervention strategy.
Multimodality Imaging of IL-18–Binding Protein-Fc Therapy of Experimental Lung Metastasis
Authors: Qizhen Cao, Weibo Cai, Gang Niu, Lina He, Xiaoyuan Chen
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Interleukin (IL)-18 plays important roles in cancer progression and metastasis. The goal of this study is to identify cell lines that are most sensitive to stand alone IL-18–binding protein (IL-18bp)-Fc treatment, to study the pharmacokinetics and tumor targeting efficiency of IL-18bp-Fc, and to evaluate the efficacy of IL-18bp-Fc in treating breast cancer experimental lung metastasis by multimodality imaging. Experimental Design: Reverse transcription-PCR, ELISA, and other cell-based assays were done on murine 4T1, CT-26, and B16F10 cells. The most IL-18bp-Fc–sensitive 4T1 cells were stably transfected with firefly luciferase (fLuc) and injected i.v. into female BALB/C mice to establish the experimental lung metastasis model. Tumor targeting efficiency and pharmacokinetics of IL-18bp-Fc was assessed by 64Cu-DOTA-IL-18bp-Fc positron emission tomography (PET) and biodistribution studies. Two groups of fLuc-4T1 experimental lung metastasis tumor-bearing mice were each given saline or IL-18bp-Fc (1 mg/kg) daily i.p. Bioluminescence imaging, 18F-FDG PET, and computed tomography scans were done to evaluate the treatment efficacy. Ex vivo experiments were also carried out to validate the imaging results. Results: IL-18bp-Fc had high and specific accumulation in the fLuc-4T1 lung metastasis tumor as evidenced by both PET and biodistribution studies. Bioluminescence imaging, 18F-FDG PET, and computed tomography scans all revealed that IL-18bp-Fc treatment was effective in inhibiting the lung metastasis tumor progression, validated by ex vivo examination of the lung. Conclusions: IL-18bp-Fc therapy can inhibit 4T1 breast cancer experimental lung metastasis. Noninvasive multimodality molecular imaging is a powerful tool for evaluating the tumor targeting efficiency/pharmacokinetics of the drug and effective monitoring of the therapeutic response.
Therapeutic differentiation and maturation of lymphatic vessels after lymph node dissection and transplantation
Authors: Tuomas Tammela, Anne Saaristo, Tanja Holopainen, Johannes Lyytikkä, Anna Kotronen, Miia Pitkonen, Usama Abo-Ramadan, Seppo Ylä-Herttuala, Tatiana V Petrova, Kari Alitalo
Journal: Nature Medicine (2007)
Low avidity antibodies to double stranded DNA in systemic lupus erythematosus: a longitudinal study of their clinical significance.
Authors: J C Nossent, V Huysen, R J Smeenk, A J Swaak
Journal: Annals of the Rheumatic Diseases (1989)

In a longitudinal study the relevance of the detection of low avidity antibodies to double stranded DNA (dsDNA) as measured by the polyethylene glycol (PEG) assay in patients with systemic lupus erythematosus (SLE) was evaluated. It was found that 35 patients positive in the PEG assay only--that is, having only low avidity anti-dsDNA in their circulation, had a mild course of their SLE with absence of renal involvement. The PEG assay had little predictive value but a high specificity (90.2%) for clinical exacerbations; furthermore, a change in avidity of anti-dsDNA in such patients was seldom observed. In 14 patients positive in both Farr and PEG assays--that is, with a relative preponderance of high avidity anti-dsDNA, there was a clear correlation between rises in Farr assay and major exacerbations, while the PEG assay on its own was not helpful in predicting disease manifestations; disease manifestations were often heralded by a change in the Farr/PEG ratio, with renal and cerebral exacerbations associated with the greatest increase in the Farr/PEG ratio (more than 10 times the previous value).