tbuckley/cabot-search huggingface dataset:
Chest pain and coronary heart disease mortality among older men and women in three communities.
Authors: A Z LaCroix, J M Guralnik, J D Curb, R B Wallace, A M Ostfeld, C H Hennekens
Journal: Circulation (1990)

Angina pectoris is a manifestation of coronary heart disease, yet little is known from clinical or epidemiologic studies about its prognosis in older populations. We investigated the relation of uncomplicated angina symptoms to risk of coronary heart disease mortality within 3 years in a prospective study of 8,359 people aged 65 and older residing in three communities. From baseline (1981-1983) to the third year of follow-up (1984-1986), there were 245 deaths from coronary heart disease. Three classifications of chest pain were defined using the Rose Questionnaire: nonexertional chest pain, chest pain on exertion (including angina), and angina. Exertional chest pain was a strong, independent predictor of coronary heart disease death for older men and women. There were no differences in the prognostic implications of this symptom between the sexes; the relative risks being 2.4 (95% confidence interval, 1.4-4.4) in men and 2.7 (1.7-4.2) in women. The risk of coronary heart disease mortality for those reporting chest pain on exertion was at least as high as that for participants whose symptoms met the Rose Questionnaire criteria for angina. The association between exertional chest pain and coronary heart disease mortality was independent of other coronary risk factors. The relation was specific for deaths from coronary heart disease, as there was no association between exertional chest pain and noncoronary causes of death. Chest pain on exertion conveys important prognostic information about risk of coronary death in older populations, regardless of gender.
Reduced hGC-1 Protein Expression Is Associated with Malignant Progression of Colon Carcinoma
Authors: Wenli Liu, Yueqin Liu, Jianqiong Zhu, Elizabeth Wright, Ivan Ding, Griffin P. Rodgers
Journal: Clinical Cancer Research (2008)

Abstract Purpose: hGC-1 (human granulocyte colony–stimulating factor–stimulated clone 1) is a gastrointestinal protein that is a member of the olfactomedin glycoprotein family. Its biological function remains poorly understood. Aberrant expression of hGC-1 in some human carcinomas has been recently reported. The purpose of this study was to examine hGC-1 expression in colon carcinoma and explore the relationship between hGC-1 expression and the clinicopathologic features of patients with colon cancer. Experimental Design: The expression of hGC-1 in colon adenocarcinoma tissues was examined by dot-blot analysis, in situ hybridization, and immunohistochemistry. The association of hGC-1 expression pattern with patient differentiation grade, tumor stage, metastasis, and survival were examined. To further investigate the involvement of hGC-1 in colon cancer progression, human colon carcinoma (HT-29) cells overexpressing hGC-1 were established and cell proliferation, adhesion, and migration were studied. Results: Compared with normal colon mucosa, the up-regulation of hGC-1 was more frequently detected in more differentiated colon cancers, whereas down-regulation or no expression was associated with poorly differentiated colon cancers. Interestingly, hGC-1 down-regulation was also found in late tumor-node-metastasis stage, metastasis, and in patients with shorter survival. The morphology and cortical actin distribution of HT-29 cells were altered by hGC-1 overexpression. However, this did not change cell proliferation, but decreased cell adhesion and migration. Conclusion: Our findings indicate that hGC-1 is involved in colon cancer adhesion and metastasis, and that hGC-1 may be a useful marker for tumor differentiation and progression of human colon carcinoma.
Results of the Rhinoconjunctivitis Related Quality of Life Questionnaire Administered to Subjects with Seasonal Allergic Rhinitis Following Treatment with Ciclesonide Hydrofluoroalkane Nasal Aerosol
Authors: C. Andrews, P. Ratner, B. Martin, W. Howland, H. Huang, S.Y. Desai, F. Bode
Journal: Journal of Allergy and Clinical Immunology (2011)
Clonality and specificity of cryoglobulins associated with HCV: pathophysiological implications
Authors: Mario U. Mondelli, Irene Zorzoli, Antonella Cerino, Agostino Cividini, Morena Bissolati, Laura Segagni, Vittorio Perfetti, Ernesto Anesi, Pietro Garini, Giampaolo Merlini
Journal: Journal of Hepatology (1998)
A Double Hit to Kill Tumor and Endothelial Cells by TRAIL and Antiangiogenic 3TSR
Authors: Bin Ren, Keli Song, Sareh Parangi, Taiguang Jin, Min Ye, Robin Humphreys, Mark Duquette, Xuefeng Zhang, Nordine Benhaga, Jack Lawler, Roya Khosravi-Far
Journal: Cancer Research (2009)

As tumor development relies on a coordination of angiogenesis and tumor growth, an efficient antitumor strategy should target both the tumor and its associated vessels. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in a tumor-selective manner. Additionally, thrombospondin-1, a naturally occurring inhibitor of angiogenesis, and a recombinant protein containing functional domains of thrombospondin-1, 3TSR, have been shown to be necessary and sufficient to inhibit tumor angiogenesis. Here, we show that a combination of a TRAIL receptor 2 agonist antibody, Lexatumumab, and 3TSR results in a significantly enhanced and durable tumor inhibition. We further observed that 3TSR induces apoptosis in primary endothelial cells by up-regulating the expression of TRAIL receptors 1 and 2 in a CD36 and Jun NH(2)-terminal kinase-dependent manner leading to the activation of both intrinsic and extrinsic apoptotic machineries. The modulation of these pathways is critical for 3TSR-induced apoptosis as disrupting either via specific inhibitors reduced apoptosis. Moreover, 3TSR attenuates the Akt survival pathway. These studies indicate that 3TSR plays a critical role in regulating the proapoptotic signaling pathways that control growth and death in endothelial cells and that a combination of TRAIL and 3TSR acts as a double hit against tumor and tumor-associated vessels.
Severe hyponatraemia in hospital inpatients.
Authors: P G Kennedy, D M Mitchell, B I Hoffbrand
Journal: BMJ (1978)

A prospective study of severe hyponatraemia in adult hospital inpatients showed that 44 patients had plasma sodium concentrations below 125 mmol(mEq)/1. Eighteen cases (41%) were iatrogenic, caused by diuretic treatment or postoperative administration of intravenous 5% dextrose, or both. Chest infection, a seldom-recognised and ill-understood cause of hyponatraemia, proved more common than carcinoma of the bronchus. Thirty-one patients had symptoms attributable to the hyponatraemia, but these were severe in only five cases. Analysis of blood and urine was of no value in distinguishing the different diagnostic groups in an emergency.
Circulatory Responses to Graded Stimulation of the Carotid Chemoreceptors in the Dog
Authors: Conrad L. Pelletier
Journal: Circulation Research (1972)

The vascular effects of graded stimulation of the carotid chemoreceptors were studied in 13 anesthetized and artificially ventilated dogs, and stimulus-response curves were defined. The carotid bifurcations were isolated and perfused at constant pressure, and the vagi were cut. Autologous blood collected in a reservoir was equilibrated at Po 2 varying from 104 to 34 mm Hg, Pco 2 from 39 to 81 mm Hg, and pH from 7.46 to 6.87 and was used to stimulate the carotid chemoreceptors. Systemic arterial Po 2 , Pco 2 , and pH were kept normal. Reflex increases in aortic blood pressure and in hind-limb perfusion pressure (constant-flow perfusion) were first seen with Po 2 of 70 mm Hg or Pco 2 &gt; 39 mm Hg. The vascular responses increased linearly with lower Po 2 or higher Pco 2 , until tensions of 34 and 71 mm Hg, respectively, were reached. These stimuli caused a reflex dilatation of the perfused saphenous vein that was also proportional to the degree of stimulation. Increasing the pH of the blood perfusing the chemoreceptors decreased these changes by more than 50%; decreases in pH, with normal Po 2 and Pco 2 , caused marked vascular responses, indicating an important role of pH in the activation of the chemoreflex mechanism.
Opioids As Modulators of Cell Death and Survival—Unraveling Mechanisms and Revealing New Indications
Authors: Irmgard Tegeder, Gerd Geisslinger
Journal: Pharmacological Reviews (2004)

Opioids are powerful analgesics but also drugs of abuse. Because opioid addicts are susceptible to certain infections, opioids have been suspected to suppress the immune response. This was supported by the finding that various immune-competent cells express opioid receptors and undergo apoptosis when treated with opioid alkaloids. Recent evidence suggests that opioids may also effect neuronal survival and proliferation or migrating properties of tumor cells. A multitude of signaling pathways has been suggested to be involved in these extra-analgesic effects of opioids. Growth-promoting effects were found to be mediated through Akt and Erk signaling cascades. Death-promoting effects have been ascribed to inhibition of nuclear factor-kappaB, increase of Fas expression, p53 stabilization, cytokine and chemokine release, and activation of nitric oxide synthase, p38, and c-Jun-N-terminal kinase. Some of the observed effects were inhibited with opioid receptor antagonists or pertussis toxin; others were unaffected. It is still unclear whether these properties are mediated through typical opioid receptor activation and inhibitory G-protein-signaling. The present review tries to unravel controversial findings and provides a hypothesis that may help to integrate diverse results.
Cyclooxygenase-2 Is an Independent Prognostic Factor in Gastric Carcinoma Patients Receiving Adjuvant Chemotherapy and Is Not Associated with EBV Infection
Authors: Eun Soo Park, In Gu Do, Cheol Keun Park, Won Ki Kang, Jae Hyung Noh, Tae Sung Sohn, Sung Kim, Min-Ji Kim, Kyoung-Mee Kim
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Cyclooxygenase-2 (COX-2) is believed to be involved in carcinogenesis in patients with chronic gastritis with Helicobacter pylori infection. EBV is detected in ∼10% of gastric carcinomas and H. pylori induces EBV reactivation in the gastric epithelium. We aimed to evaluate significance of COX-2 in gastric carcinoma occurred in EBV and H. pylori prevalent area. Experimental Design: Tissue microarray samples from 457 gastric carcinoma patients who underwent gastrectomy and adjuvant chemotherapy were studied with EBER1 in situ hybridization for EBV and immunohistochemistry for COX-2 and other gastric carcinoma-related proteins (hMLH1, E-cadherin, c-erbB, and cyclin D1). Results: EBV infection was observed in 10.9% of gastric carcinomas and was associated with proximal tumor location, increased numbers of lymph node, and E-cadherin expression (P &amp;lt; 0.01). COX-2 overexpression was closely associated with intestinal histologic type and lower tumor stage (P = 0.01). Univariate analysis showed that pT, pN, lymph node ratio, American Joint Committee on Cancer stage, numbers of negative lymph nodes, and resection margin &amp;lt;1 cm were significant prognostic factors. The Cox proportional hazards regression analysis indicated that lack of COX-2 expression and resection margin &amp;lt;1 cm were independent prognostic factors for disease-free survival (P = 0.008 and 0.03, respectively) and overall survival (P = 0.01 and 0.007, respectively). Conclusions: EBV infection is not associated with COX-2 expression or survival in gastric carcinoma. Lack of COX-2 expression is an independent prognostic factor in both overall and disease-free survival in gastric carcinoma. Our results indicate that COX-2 may play a role in the progression of gastric carcinoma regardless of EBV infection and is closely associated with histologic differentiation and prognosis.
Effects of Losartan on Cardiovascular Morbidity and Mortality in Patients With Isolated Systolic Hypertension and Left Ventricular Hypertrophy
Authors: Sverre E. Kjeldsen, Björn Dahlöf, Richard B. Devereux, Stevo Julius, Peter Aurup, Jonathan Edelman, Gareth Beevers, Ulf de Faire, Frej Fyhrquist, Hans Ibsen, Krister Kristianson, Ole Lederballe-Pedersen, Lars H. Lindholm, Markku S. Nieminen, Per Omvik, Suzanne Oparil, Steven Snapinn, Hans Wedel, None for the LIFE Study Group
Journal: JAMA (2002)

ContextDrug intervention in placebo-controlled trials has been beneficial in isolated systolic hypertension.ObjectiveTo test the hypothesis that losartan improves outcome better than atenolol in patients with isolated systolic hypertension and electrocardiographically documented left ventricular hypertrophy (ECG-LVH).DesignDouble-blind, randomized, parallel-group study conducted in 1995-2001.Setting and ParticipantsA total of 1326 men and women aged 55 through 80 years (mean, 70 years) with systolic blood pressure of 160 to 200 mm Hg and diastolic blood pressure of less than 90 mm Hg (mean, 174/83 mm Hg) and ECG-LVH, recruited from 945 outpatient settings in the Nordic countries, the United Kingdom, and the United States.InterventionsPatients were randomly assigned to receive once-daily losartan (n = 660) or atenolol (n = 666) with hydrochlorothiazide as the second agent in both arms, for a mean of 4.7 years.Main Outcome MeasureComposite end point of cardiovascular death, stroke, or myocardial infarction.ResultsBlood pressure was reduced by 28/9 and 28/9 mm Hg in the losartan and atenolol arms. The main outcome was reduced by 25% with losartan compared with atenolol, 25.1 vs 35.4 events per 1000 patient-years (relative risk [RR], 0.75; 95% confidence interval [CI], 0.56-1.01; P = .06, adjusted for risk and degree of ECG-LVH; unadjusted RR, 0.71; 95% CI, 0.53-0.95; P = .02). Patients receiving losartan had reductions in the following without a difference in the incidence of myocardial infarction: cardiovascular mortality (8.7 vs 16.9 events per 1000 patient-years; RR, 0.54; 95% CI, 0.34-0.87; P = .01), nonfatal and fatal stroke (10.6 vs 18.9 events per 1000 patient-years; RR, 0.60; 95% CI, 0.38-0.92; P = .02), new-onset diabetes (12.6 vs 20.1 events per 1000 patient-years; RR, 0.62; 95% CI, 0.40-0.97; P = .04), and total mortality (21.2 vs 30.2 events per 1000 patient-years; RR, 0.72; 95% CI, 0.53-1.00; P = .046). Losartan decreased ECG-LVH more than atenolol (P&lt;.001) and was better tolerated.ConclusionThese data suggest that losartan is superior to atenolol for treatment of patients with isolated systolic hypertension and ECG-LVH.
Sexual Problems in Younger Women After Breast Cancer Surgery
Authors: Stephanie R. Burwell, L. Douglas Case, Carolyn Kaelin, Nancy E. Avis
Journal: Journal of Clinical Oncology (2006)

To examine sexual problems in younger women diagnosed with breast cancer during the first year after surgery and to identify sociodemographic, medical, and psychosocial predictors of sexual problems.Women diagnosed with breast cancer age < or = 50 years completed surveys at three time points: within 24 weeks after initial surgery (baseline), 6 weeks after baseline, and 6 months later. Survey items included the Medical Outcomes Study Sexual Functioning Scale, satisfaction with sex life, feeling sexually attractive, body image, marital satisfaction, quality of life, medical history, symptoms, and sociodemographics. Prediagnosis sexual problems were retrospectively ascertained at the initial survey.Analyses included 209 women sexually active at baseline (78.6% of total sample). Sexual problems were significantly greater immediately postsurgery compared with retrospective reports before diagnosis (P < .0001). Although problems gradually decreased over time, they were still greater at 1 year postsurgery than before diagnosis. In multivariate analyses controlling for sexual problems at prediagnosis, vaginal dryness, and lower perceived sexual attractiveness were consistently related to greater overall sexual problems. Chemotherapy was related to sexual problems only at baseline except for women who became menopausal as a result of chemotherapy, who continued to have problems.Findings substantiate the need to address potential sexual problems related to chemotherapy treatment and menopause among younger breast cancer survivors and to counsel women about possible remedies, particularly for vaginal dryness. Increasing feelings of sexual attractiveness may also help sexual problems, especially among women for whom these feelings were altered by surgery or treatment.
Gentamicin Serum Concentrations: Pharmacokinetic Predictions
Authors: Hull Jh, Sarubbi Fa
Journal: Annals of Internal Medicine (1976)

Recent studies that emphasize the unpredictability of gentamicin serum concentrations have cast doubt on the accuracy of commonly used dosing nomograms. We therefore developed a digital computer program to evaluate gentamicin pharmacokinetics and have tested its ability to predict correctly gentamicin serum levels under clinical conditions. A significant relation (P < .001) was found between 130 measured (bioassayed) and computer predicted levels from 40 patients. Serum levels were reliably estimated in patients with unstable renal function and were statistically, but not clinically, affected by changes in hematocrit. The calculation of volume of distribution on the basis of the patient's lean body weight rather than total body weight was an important factor that contributed to the accuracy of the predicted level. A new dosing chart is presented that incorporates the important variables affecting gentamicin pharmacokinetics into an easily used, convenient form.
Antiapoptotic Activity of Autocrine Interleukin-22 and Therapeutic Effects of Interleukin-22-Small Interfering RNA on Human Lung Cancer Xenografts
Authors: Weici Zhang, Yongyan Chen, Haiming Wei, Chaogu Zheng, Rui Sun, Jian Zhang, Zhigang Tian
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Non–small cell lung carcinoma (NSCLC) is one of most common malignant diseases and usually is resistant against apoptosis-inducing chemotherapy. This study is to explore the antiapoptotic mechanisms of interleukin (IL)-22 in human lung cancer. Experimental Design: Nineteen cases with stage I to III NSCLC were collected to determine the expression of IL-22. Stable transfection of human IL-22 cDNA into A549 and PG cells and transfection of IL-22-RNA interference (RNAi) into these cancer cell lines were done to reveal the molecular mechanisms of IL-22. Results: It was found that IL-22 was highly expressed in primary tumor tissue, malignant pleural effusion, and serum of patients with NSCLC. IL-22R1 mRNA was also detected in lung cancer tissues as well as lung cancer cell lines. Overexpression of IL-22 protected lung cancer cell lines from serum starvation-induced and chemotherapeutic drug-induced apoptosis via activation of STAT3 and its downstream antiapoptotic proteins such as Bcl-2 and Bcl-xL and inactivation of extracellular signal-regulated kinase 1/2. Exposure to blocking antibodies against IL-22R1 or transfection with the IL-22-RNAi plasmid in vitro resulted in apoptosis of these lung cancer cells via STAT3 and extracellular signal-regulated kinase 1/2 pathways. Furthermore, an in vivo xenograft study showed that administration of IL-22-RNAi plasmids significantly inhibited the human tumor cell growth in BALB/c nude mice. Conclusions: Our study indicates that autocrine production of IL-22 contributes to human lung cancer cell survival and resistance to chemotherapy through the up-regulation of antiapoptotic proteins.
Anemia Is a Significant Prognostic Factor in Local Relapse-Free Survival of Premenopausal Primary Breast Cancer Patients Receiving Adjuvant Cyclophosphamide/Methotrexate/5-Fluorouracil Chemotherapy
Authors: Peter Dubsky, Paul Sevelda, Raimund Jakesz, Hubert Hausmaninger, Hellmut Samonigg, Michael Seifert, Ursula Denison, Brigitte Mlineritsch, Günther Steger, Werner Kwasny, Herbert Stöger, Rupert Bartsch, Michael Stierer, Susanne Taucher, Michael Fridrik, Walter Schippinger, Richard Greil, Richard Pötter, Michael Gnant
Journal: Clinical Cancer Research (2008)

Abstract Purpose: To determine the effects of anemia on local relapse-free, relapse-free, and overall survival (LRFS, RFS, and OS, respectively) in premenopausal, primary breast cancer patients receiving adjuvant polychemotherapy, and to determine which conventional prognostic factors affected these outcomes. Experimental Design: Four hundred twenty-four premenopausal patients with early-stage primary breast cancer and hormone receptor–expressing tumors were treated with i.v. cyclophosphamide/methotrexate/5-fluorouracil (CMF) polychemotherapy as part of an adjuvant phase III trial (Austrian Breast and Colorectal Cancer Study Group Trial 5). The influence of anemia (hemoglobin &amp;lt;12 g/dL) on LRFS, RFS, and OS was evaluated in a retrospective analysis. Results: Of 424 patients, 77 (18.2%) developed anemia on CMF chemotherapy. After a median follow-up time of 5 years, 8.9% of nonanemic patients had local relapse compared with 19.6% of anemic patients (P = 0.0006). Although mastectomy was associated with anemia (26% versus 13.7% in breast conserving surgery; P = 0.002), multivariate analysis did not show mastectomy per se to be a significant risk factor for LRFS. Age, lymph node status, and hemoglobin had an independent significant influence on LRFS (P &amp;lt; 0.005). Anemic patients had a relative risk of 2.96 (95% confidence interval, 1.41-6.23) for developing local relapse in comparison with nonanemic patients. Conclusion: Premenopausal breast cancer patients who developed anemia during the CMF regimen had significantly worse LRFS. In Austrian Breast and Colorectal Cancer Study Group Trial 5, anemia may have contributed to an almost doubled incidence of local recurrence in the chemotherapy arm. Molecular targets associated with tumor hypoxia and distinct from erythropoiesis should receive further attention in experimental and clinical settings.
Effects of long term alcohol ingestion on glutathione metabolising enzymes and taurine contents in the myocardium of rats
Authors: I. EDES, G. PIROS, G. K TOTH, M. CSANADY, K. KOVACS
Journal: Cardiovascular Research (1986)

The effects of long term intake of dietary alcohol on myocardial glutathione metabolism and taurine content were studied in rats. Alcohol, comprising more than 30% of the dietary calorie content, was administered to male CFY rats for six weeks. Compared with the controls, the left ventricle of the alcohol treated animals had an increased taurine content (18.4(2.6) vs 13.1(2.5) μmol·g wet weight−1) and a slightly, but not significantly, decreased reduced glutathione content. To assess the glutathione metabolism in the myocardium, the activities of glutathione reductase, glutathione peroxidase, glutathione-S-transferase, γ-glutamylcysteine synthetase, and glutathione synthetase were measured. Significant increases were found in the activities of glutathione reductase (0.65(0.03) U.g wet weight−1 in the controls and 0.80(0.05) U.g wet weight−1 in the alcohol treated rats) and glutathione-peroxidase after six weeks of alcohol ingestion. Only slight, non-significant changes were found for the other enzymes investigated. It is thus apparent that in the myocardium of rats treated long term with ethanol the previously observed enhanced lipoperoxidation is not necessarily associated with severe glutathione depletion, and an increase in the activity of glutathione reductase might be responsible, at least in part, for the preservation of glutathione.