tbuckley/cabot-search huggingface dataset:
The lowest X4 Geno2Pheno false-positive rate is associated with greater CD4 depletion in HIV-1 infected patients
Authors: M.M. Santoro, D. Armenia, L. Fabeni, M. Santoro, C. Gori, F. Forbici, V. Svicher, A. Bertoli, L. Dori, M. Surdo, E. Balestra, G. Palamara, E. Girardi, G. Angarano, M. Andreoni, P. Narciso, A. Antinori, F. Ceccherini-Silberstein, C.F. Perno
Journal: Clinical Microbiology and Infection (2012)
Activation of Epithelial Sodium Channels by Prostasin in Xenopus Oocytes
Authors: MASATAKA ADACHI, KENICHIRO KITAMURA, TAKU MIYOSHI, TAKEFUMI NARIKIYO, KOZO IWASHITA, NAOKI SHIRAISHI, HIROSHI NONOGUCHI, KIMIO TOMITA
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Prostasin, a novel serine protease, was purified from seminal fluid, and its cDNA sequence was determined. Expression of prostasin was detected in human tissues, including prostate, kidney, and lung, as well as bodily fluids, including seminal fluid and urine. However, its physiologic role in the human body is not known. Recently, a novel regulatory mechanism by which serine proteases activate epithelial sodium channel in the Xenopus oocyte was identified. Therefore, it was hypothesized that prostasin could activate sodium currents, and a rat prostasin cDNA clone was isolated to investigate its physiologic function. Rat prostasin mRNA is expressed predominantly in kidney, and lower levels of expression were detected in prostate, lung, colon, stomach, and skin. These all are epithelial tissues in which the epithelial sodium channel (ENaC) is expressed. Coexpression of rat prostasin and rat ENaC in Xenopus oocytes increased the amiloride-sensitive sodium current by twofold. Preincubation of oocytes that expressed prostasin with aprotinin did not result in an increase in sodium current, compared with the control. The removal of aprotinin from the bath solution resulted in a twofold increase of the current only in oocytes that expressed prostasin, which indicates that protease activity of prostasin is required for the ENaC activation. Expression of rat prostasin had no effect on the potassium current when expressed with rat renal outer medulla K channel, which shows specificity of prostasin action for ENaC. These results indicate that prostasin acts as an extracellular regulator of ENaC.
Rivaroxaban in Patients Stabilized After a ST-Segment Elevation Myocardial Infarction
Authors: Jessica L. Mega, Eugene Braunwald, Sabina A. Murphy, Alexei N. Plotnikov, Paul Burton, Robert Gabor Kiss, Alexander Parkhomenko, Michal Tendera, Petr Widimsky, C. Michael Gibson
Journal: Journal of the American College of Cardiology (2013)
Chemodectomas in Dogs: Epidemiologic Comparisons With Man2
Authors: Howard M. Hayes, Joseph F. Fraumeni
Journal: JNCI Journal of the National Cancer Institute (1974)

Fifty dogs with a confirmed diagnosis of chemodectoma were identified at 11 veterinary school clinic-hospitals. As in man, some evidence was found of genetic determinants: 2 brachycephalic breeds (Boston terriers and boxers) had a significantly greater risk compared to all other purebred dogs combined. An excessive risk was detected in males, though it was not statistically significant, and in older dogs. There was a significantly high frequency of 4 concurrent tumors (seminoma and interstitial-cell tumors of the testis, adenomatous thyroid neoplasms, and hemangiomas); but in man, with chemodectoma, the reported tendency to multiple primary tumors has been confined to the chemoreceptor system. The etiologic role of chronic hypoxia, suggested by the high incidence of carotid body tumors among Peruvians in the Andes, may be clarified by further studies of chemodectoma in brachycephalic breeds.
Modulation of sympathetic activity and heart rate variability by ivabradine
Authors: Valdo Jose Dias da Silva, Eleonora Tobaldini, Marcella Rocchetti, Maddalena A. Wu, Gabriella Malfatto, Nicola Montano, Antonio Zaza
Journal: Cardiovascular Research (2015)

Bradycardic agents are currently used in the treatment of angina and heart failure; direct information on their effects on cardiac sympathetic nerve activity (SNA) may be relevant to their chronic use. The present study evaluates the effect of pacemaker inhibition on SNA; direct nerve recordings and indirect autonomic indexes are compared. Experiments were performed in 18 anaesthetized rats. SNA (direct nerve recording) and heart rate variability (HRV) indexes were evaluated in parallel. All parameters were recorded 10 min before to 60 min after administration of the If blocker ivabradine (IVA; 2 mg/kg, i.v.; n = 8) or vehicle (VEH; n = 5). IVA-induced RR interval (RR) prolongation (at 60 min +15.0 ± 7.1%, P < 0.01) was associated with decreased diastolic arterial pressure (DAP; −17.3 ± 8.4%, P < 0.05) and increased SNA (+51.1 ± 12.3%, P < 0.05). These effects were accompanied by increased RR variance (RRσ2), which showed strong positive correlation with RR. Frequency-domain HRV indexes (in normalized units) were unchanged by IVA. After baroreceptor reflexes had been eliminated by sino-aortic denervation (n = 5), similar IVA-induced RR prolongation (at 60 min +14.3 ± 5.9%, NS vs. intact) was associated with a larger DAP reduction (−30.9 ± 4.1%, P < 0.05 vs. intact), but failed to affect SNA. (i) IVA-induced bradycardia was associated with increased SNA, resulting from baroreceptor unloading; if this applied to chronic IVA use in humans, it would be of relevance for therapeutic use of the drug. (ii) Whenever mean HR is concomitantly changed, time-domain HRV indexes should not be unequivocally interpreted in terms of autonomic balance.
Cigarette Smoking and Cancers of the Urinary Tract: Geographic Variation in the United States&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Joseph F. Fraumeni
Journal: JNCI Journal of the National Cancer Institute (1968)

Variation in bladder cancer mortality among States was highly correlated (r = +0.73) with the per capita cigarette sales estimated from State tax revenues. This relationship was independent of urbanization and similar in magnitude to that observed between cigarette consumption and cancer of the respiratory tract. In contrast, leukemia showed no correlation with cigarette consumption, whereas kidney cancer had an intermediate but significant relationship (r = +0.49). These findings are consistent with other evidence relating the distribution of bladder cancer to smoking patterns of the population, and suggest that cancers of the upper urinary tract may also be associated with cigarette smoking.
Transforming growth factor-beta1 (TGF-β1) expression is related to reticular basement membrane (Rbm) hypervascularity in smokers and COPD
Authors: Sukhwinder Singh Sohal, Amir Soltani, David Reid, Steven Weston, Hans Konrad Muller, Richard Wood-Baker, Eugene Haydn Walters
Journal: European Respiratory Journal (2012)

Introduction:  TGF-β1 is likely to play an important role in COPD airway pathology, including angiogenesis and epithelial mesenchymal transition (EMT), but it is relatively under-investigated in this condition. We have previously published that the Rbm is fragmented as a likely marker of active EMT and hyper-vascular in the airways of current smokers either with or without COPD.   Objective:  This study evaluated the status of TGF-β1 in endobronchial biopsies (ebb) from smokers with or without COPD.   Methods:  Ebb sections from 15 smokers with normal lung function (S-NLF), 19 current (CS) and 14 ex-smokers (ES) with COPD were immunostained for TGF-β1 and compared to 17 normal controls (NC). The percentage area of tissue and the number and area of vessels and also the percentage of vessels staining positively for TGF-β1 were compared between groups.   Results:  There were no differences between groups in epithelial TGF-β1 staining. TGF-β1 stained vessels in the Rbm were increased in S-NLF, CS-COPD and ES-COPD compared to NC, but especially so in CS-COPD [median (range) for number of vessels/mm Rbm 2.5 (0.0-12.7), 3.4 (0.0-8.1) and 1.0 (0.0-6.3) vs. 0.0 (0.0-7.0), p   Conclusions:  Vessel-associated TGF-β1 was increased in smokers and COPD, but especially in CS-COPD. This is likely to be relative to the pathogenesis of COPD; EMT, structural remodelling, angiogenesis and tumorigenesis.
Low indoleamine 2,3‐dioxygenase activity in persistent food allergy in children
Authors: B. Buyuktiryaki, U. M. Sahiner, G. Girgin, E. Birben, O. U. Soyer, O. Cavkaytar, C. Cetin, E. Arik Yilmaz, S. T. Yavuz, O. Kalayci, T. Baydar, C. Sackesen
Journal: Allergy (2015)

Indoleamine 2,3-dioxygenase (IDO), which degrades tryptophan (Trp) to kynurenine (Kyn), has been demonstrated to contribute to modulation of allergic responses. However, the role of IDO in food allergy has not yet been elucidated.Serum Trp and Kyn concentrations were analyzed by high-pressure liquid chromatography. Expression of IDO gene was measured by real-time PCR. The levels of interleukin (IL)-4, IL-10, and interferon (IFN)-γ in cell culture supernatants were measured by ELISA.Kyn/Trp (IDO activity) was significantly lower in subjects with food allergy (n = 100) than in aged-matched healthy controls (n = 112) (P = 0.004). Kyn/Trp was decreased from healthy through completely tolerant, partially tolerant, and reactive ones [LN transformation (mean ± SEM) healthy: 3.9 ± 0.02 μM/mM; completely tolerant: 3.83 ± 0.04; partially tolerant: 3.8 ± 0.06; reactive: 3.7 ± 0.04] (P = 0.008). The frequency of genetic polymorphisms of IDO did not reveal a significant association with Trp, Kyn, and Kyn/Trp in healthy and food-allergic cases. Culture of PBMC experiments yielded that IDO mRNA expression was not different between tolerant and reactive groups. IL-4 synthesis when stimulated with casein increased significantly in subjects who are reactive and tolerant to foods (P = 0.042, P = 0.006, respectively). Increase in IL-10 synthesis was observed only in children tolerant to milk, but not in reactive ones. IFN-γ synthesis, when stimulated with IL-2 and β-lactoglobulin in cell culture, was significantly higher in subjects tolerant to milk than in the reactive ones (P = 0.005 and P = 0.029, respectively).Our results imply the probability of involvement of IDO in development of tolerance process, and we presume that high IDO activity is associated with nonresponsiveness to food allergens despite allergen sensitization.
Circadian cancer therapy.
Authors: W J Hrushesky, G A Bjarnason
Journal: Journal of Clinical Oncology (1993)

PURPOSE AND DESIGN: To review briefly the growing body of published data about circadian variation in cytotoxic drug metabolism and tissue sensitivity to chemotherapeutic agents. The suggestion that toxicity may be reduced and anticancer efficacy improved by administering antineoplastic agents at carefully selected times of the day was assessed. RESULTS AND CONCLUSION: The medical literature describing molecular, cellular, and organismic time-keeping mechanisms, as well as circadian rhythms, in cytokinetic, pharmacokinetic, and pharmacodynamic parameters relevant to cancer chemotherapy, which support the predictable rhythmic relationship between dose and effect that occurs during each day, were reviewed. Advantages for optimal circadian scheduling have been demonstrated for diminishing side effects and increasing maximal safe dose-intensity of drugs of diverse class. The use of the predictable circadian relationship of dose and response provides another increment of progress in the treatment of cancer patients.
Secondary acute myeloid leukemia in children previously treated with alkylating agents, intercalating topoisomerase II inhibitors, and irradiation.
Authors: C Sandoval, C H Pui, L C Bowman, D Heaton, C A Hurwitz, S C Raimondi, F G Behm, D R Head
Journal: Journal of Clinical Oncology (1993)

Patient records were reviewed to identify cases of secondary acute myeloid leukemia (AML) with clinical and cytogenetic features characteristic of classic epipodophyllotoxin-related AML in patients whose prior treatment for cancer did not include these agents.Four cases of secondary AML with chromosomal abnormalities involving bands 11q23 and 21q22, in the absence of prior treatment with etoposide or teniposide, were identified among patients treated at St Jude Children's Research Hospital between January 1980 and April 1992.The four identified patients were initially treated for rhabdomyosarcoma, non-Hodgkin's lymphoma (n = 2), and Hodgkins' disease. Prior chemotherapy included relatively low cumulative doses of doxorubicin (median, 150 mg/m2; range, 120 to 375 mg/m2) and cyclophosphamide (median, 3,100 mg/m2; range, 2,250 to 11,400 mg/m2). All four patients had received radiation therapy: 59.4 Gy to the right middle ear for rhabdomyosarcoma; 15 Gy and 12 Gy to the abdomen and right lower quadrant, respectively, for non-Hodgkin's lymphoma; 27 Gy to the right orbit for non-Hodgkin's lymphoma; and 36.6 Gy to the mantle-paraaortic-spleen regions plus 20.4 Gy inverted-Y radiation at relapse for Hodgkin's disease. Secondary AML was diagnosed a median of 38 months after initial diagnosis (range, 14 to 55). Leukemic cell translocations involved band 11q23 in two cases and band 21q22 in two. Although all patients obtained a complete remission (CR), only one remains disease-free (at 34 months), following an allogeneic bone marrow transplant.Intercalating topoisomerase II inhibitors (doxorubicin, dactinomycin), when combined with alkylating agents and irradiation, may cause secondary AML.
Glycolytic phenotype mapping in lung cancer cell lines
Authors: Maya Ilouze, Nir Peled
Journal: European Respiratory Journal (2012)

Background  :  It is well established that cancer cell can activate their glycolysis pathway in order to survive in hypoxia micro-environment. Tumors cells show a stinking rate of glycolysis and lactate production, even in the presence of oxygen. Importantly, some cancer cells demonstrate impaired mitochondria respiration and high glycolysis, namely  effect. It is known that most types of cancers fit the Warburg hypothesis because a decreased expression of mitochondrial ATP synthase, which is a bottleneck of mitochondrial oxidative phosphorylation.   Objective : Our overall goal is to profile the lactic acid production in lung cancer cell lines (NSCLC vs SCLC) in order to prototype the glycolytic phenotype that might be used as a diagnostic tool for the early detection of lung cancer.   Study Design and Preliminary data : Our main steps are: (1) quantify lactic acid production of representatives of NSCLC and SCLC cell lines in order to select lung cancer cell lines which demonstrate the highest glycolytic phenotype; we choose to study representative of adenocarcinoma (e.g. H2030, A549, H1563, H1650), squamous carcinoma (e.g. H226) and SCLC cell line (e.g. SHP77) (2) measure the glycolysis (e.g.GAPDH and pyruvate kinase) and oxidative phosphorylation enzymes (e.g. ATP synthase) level in order to study the glycolytic phenotype of lung cancer cell lines. Our preliminary results indicate that the adenocarcinoma cell lines, namely A549 and H2030 secreted lactic acid to the medium in concentration of 9.5nmol/ul and 11nmol/ul, respectively.   Impact:  Our study could serve as a basis for understanding the glycolytic phenotype mechanism  in vitro  and therefore for developing diagnosis test for early detection of lung cancer.
Fludarabine phosphate: a synthetic purine antimetabolite with significant activity against lymphoid malignancies.
Authors: H G Chun, B Leyland-Jones, B D Cheson
Journal: Journal of Clinical Oncology (1991)

Fludarabine phosphate is the 2-fluoro, 5'-monophosphate derivative of vidarabine (ara-A) with the advantages of resistance to deamination by adenosine deaminase (ADA) and improved solubility. The mechanism of cytotoxic action of the compound appears to involve metabolic conversion to the active triphosphate. Fludarabine phosphate has substantial activity against lymphoid malignancies, particularly chronic lymphocytic leukemia (CLL) and low-grade non-Hodgkin's lymphoma (NHL). Its single-agent activity in CLL appears at least comparable to those of other conventional combination regimens. Its activity in Hodgkin's disease, mycosis fungoides, and macroglobulinemia, although suggestive, needs to be further defined and clinical trials are warranted in hairy cell leukemia, prolymphocytic leukemia, and previously untreated myeloma. The compound does not appear active against most common solid tumors. Early clinical trials indicated significant myelosuppression and the potential for severe neurotoxicity. Toxicity on the currently used low-dose schedules includes transient and reversible myelosuppression, nausea and vomiting, diarrhea, somnolence/fatigue, and elevations of liver enzymes and/or serum creatinine. Possible pulmonary toxicity has been suggested in several patients. The currently used low-doses of fludarabine phosphate, even with repeated administration, are well tolerated and appear safe with a negligible risk for severe neurotoxicity. Based on its single-agent activity and tolerability, the Food and Drug Administration recently granted group C designation of the drug for the treatment of patients with refractory CLL outside the clinical trials setting. The use of fludarabine phosphate in combination regimens and its impact on the natural history of the lymphoid malignancies is yet to be determined. Fludarabine phosphate may well occupy a pivotal role in the management of CLL and low-grade NHL.
Air pollution levels, meteorological conditions and asthma symptoms
Authors: B Forsberg, N Stjernberg, M Falk, B Lundback, S Wall
Journal: European Respiratory Journal (1993)

We wanted to assess relations between the daily occurrence of asthma symptoms and fluctuations of air pollution concentrations and meteorological conditions. In a panel of 31 asthmatic patients residing in the town of Piteå in northern Sweden, severe symptoms of shortness of breath, wheeze, cough and phlegm were recorded in an asthma diary together with suspected causes. Sulphur dioxide, nitrogen dioxide, black smoke, relative humidity and temperature were used to evaluate the relationship to the environment. By using multivariate analyses, we found that daily variations in the particulate pollution levels, indicated by black smoke levels below the criteria limits, had significant effects on the risk of developing severe symptoms of shortness of breath. This association was stronger among 10 subjects, who had at least five incident days with severe shortness of breath. Meteorological conditions were not significant in the multivariate models. Cough and phlegm did not show significant relationships to any environmental condition that was evaluated. Only one-third of the subjects reported, at least once during the study, symptoms believed to be related to air pollutants, although we found significant correlations between the pollution levels and the frequency of pollution-related symptoms. We conclude that an association has been established for black smoke as pollutant and shortness of breath as respiratory symptom, and that in certain asthmatics, effects were occurring at lower particulate levels than suggested previously.
Abstract 5794: Clinical Risk Factors to Predict Deep Venous Thrombosis Post Endovenous Laser Ablation of Saphenous Veins
Authors: Yung-Wei Chi, Lobna Ali, T. Cooper Woods
Journal: Circulation (2009)

Introduction: Endovenous laser ablation of saphenous veins is an alternative to standard surgical vein stripping for the treatment of symptomatic varicose veins. Deep venous thrombosis (DVT) has been reported as a complication of such procedure with a rate of 1 to 5 %. Clinical risk factors to predict DVT post endovenous laser ablation are not well established. Hypothesis: To establish clinical risk factors to predict DVT post endovenous laser ablation. Method: Three hundred sixty consecutive patients who underwent endovenous laser ablation of saphenous veins were followed. Duplex ultrasound was performed within 1 week of the index procedure. DVT was defined as evidence of non-compressibility involving the sapheno-femoral, sapheno-popliteal junctions or any of the deep veins. Comparison between those with and without DVT was performed using step-wise logistic regression (SAS, SAS Institute, Cary, NC) to measure the correlation between continuous and categorical variables. The continuous variables included age, weight, glomerular filtration rate, distance of laser ablation, total energy used and the categorical variables included gender, diabetes mellitus, hypertension, hyperlipidemia, prior stroke, superficial venous thrombosis (SVT), DVT, coronary artery disease, peripheral arterial disease, and pulmonary embolism. Additional iterations were performed to determine the predictive power of various age thresholds. A p value &lt; 0.05 was accepted as representing a significant difference. Result: Nineteen DVTs were found on follow up ultrasound. Eighteen cases involved either the sapheno-femoral or sapheno-popliteal junctions. Only one case involved the deep venous system. Age &gt; 66 (p = 0.007), female gender (p = 0.048) and prior history of SVT (p = 0.002) were associated with increased risk of DVT post endovenous laser ablation. Conclusion: Age &gt; 66, female gender and history of prior SVT are risk factors to predict DVT post endovenous laser ablation. Clinical Risk Factors to Predict DVT Post Endovenous Laser Ablation
Are we using the urinary legionella antigen test appropriately
Authors: Daniel Sommer, Sudhakar Koduri
Journal: European Respiratory Journal (2013)

Legionella pneumophila can cause severe respiratory infections with a mortality rate approaching 25% [1]. Diagnosing Legionella pneumonia has significant clinical and public health implications. The urinary antigen screening test used at the Pennine Acute Hospitals NHS Trust costs £21.17 and the British Thoracic Society produce strict criteria for when the test should be considered [2]. An audit was undertaken to determine the proportion of tests that are ordered appropriately within the trust.  The case notes of 32 patients who were tested towards the beginning of 2012 were analysed to determine if testing was appropriate, the results of the test and which wards were ordering these tests. 72% of tests were ordered inappropriately according to guidelines, of which 100% were negative. If the guidelines were followed, a large number of unnecessary tests could be saved.  In times of economic hardship and when the NHS is required to make £20bn in efficiency savings by 2015, it makes sense that doctors should adhere to evidence-based policy when ordering expensive tests.  We aim to educate doctors about when it is appropriate to order this test, and to change trust guidelines to reflect best practice as outlined by the BTS.  [1] Bartlett, J., Johns Hopkins Medicine ABX Guide – Legionnaire’s disease, http://www.hopkinsguides.com/hopkins/ub/view/Johns_Hopkins_ABX_Guide/540307/all/Legionnaires%26apos%3B+Disease, accessed 09-02-2013 (Updated January 2013).  [2] Macfarlane J, et al. (BTS Pneumonia Guidelines Committee). BTS Guidelines for the management of community acquired pneumonia in adults. Thorax. 2001;56. (Update published in 2004).