tbuckley/cabot-search huggingface dataset:
Identification of an alternatively spliced isoform of carbonic anhydrase XII in diffusely infiltrating astrocytic gliomas
Authors: Joonas Haapasalo, Mika Hilvo, Kristiina Nordfors, Hannu Haapasalo, Seppo Parkkila, Alise Hyrskyluoto, Immo Rantala, Abdul Waheed, William S. Sly, Silvia Pastorekova, Jaromir Pastorek, Anna-Kaisa Parkkila
Journal: Neuro-Oncology (2008)

Carbonic anhydrase XII (CA XII) is a transmembrane enzyme that is associated with neoplastic growth. CA XII has been proposed to be involved in acidification of the extracellular milieu, creating an appropriate microenvironment for rapid tumor growth. Because RNA sequence databases have indicated that two isoforms of CA XII might exist in human tissues, and because alternatively spliced protein forms have been linked to aggressive behavior of cancer cells, we designed a study to evaluate the presence of the two forms of CA XII in diffuse astrocytomas, a tumor type known for its aggressive and often noncurable behavior. Reverse transcription PCR of tumor samples surprisingly revealed that CA XII present in diffuse astrocytomas is mainly encoded by a shorter mRNA variant. We further showed by Western blotting that anti-CA XII antibody recognized both isoforms in the glioblastoma cell lines, and we then evaluated the expression of CA XII in astrocytomas using immunohistochemistry and correlated the results with various clinicopathological and molecular factors. Of 370 diffusely infiltrating astrocytomas, 363 cases (98%) showed immunoreactions for CA XII. Importantly, CA XII expression correlated with poorer patient prognosis in univariate (p = 0.010, log-rank test) and multivariate survival analyses (p = 0.039, Cox analysis). From these results, we conclude that CA XII is commonly expressed in diffuse astrocytomas and that it might be used as a biomarker of poor prognosis. The absence of 11 amino acids in the shorter isoform, which seems to be common in astrocytomas, may affect the normal quaternary structure and biological function of CA XII.
Questionnaire survey of urinary incontinence in women with cystic fibrosis
Authors: A Orr
Journal: BMJ (2001)

Cystic fibrosis is an inherited disease characterised by the production of infected secretions, and it requires lifelong daily treatment by airway clearance. We knew that some women attending our clinic for adults with cystic fibrosis leaked urine when performing airway clearance or spirometry, but they were dismissive during discussion and were rarely forthcoming about the problem. This study was designed to determine the prevalence of urinary incontinence in women with cystic fibrosis, to establish the importance of the problem as perceived by the patients, and to identify those women who wanted help.
Attenuated P2X<sub>7</sub> Pore Function as a Risk Factor for Virus-induced Loss of Asthma Control
Authors: Loren C. Denlinger, Lei Shi, Arturo Guadarrama, Kathy Schell, Dawn Green, Alison Morrin, Kirk Hogan, Ronald L. Sorkness, William W. Busse, James E. Gern
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Upper respiratory tract infection is a guideline accepted risk domain for the loss of asthma control. The ionotrophic nucleotide receptor P2X(7) regulates compartmentalized acute inflammation and the immune response to airway pathogens.We hypothesized that variability in P2X(7) function contributes to neutrophilic airway inflammation during a cold and thereby is linked to acute asthma.Research volunteers with asthma were enrolled at the onset of a naturally occurring cold and monitored through convalescence, assessing symptoms, lung function, and airway inflammation. P2X(7) pore activity in whole blood samples was measured using a genomically validated flow cytometric assay.Thirty-five participants with mild to moderate allergic asthma were enrolled and 31 completed all visits. P2X(7) pore function correlated with the change in nasal lavage neutrophil counts during the cold (R(s) = 0.514, P = 0.004) and was inversely related to the change in asthma symptoms (R(s) = -0.486, P = 0.009). The change in peak expiratory flow recordings, precold use of inhaled corticosteroids, and P2X(7) pore function were multivariate predictors of asthma symptoms (P = 0.001, < 0.001 and = 0.003 respectively). Attenuated P2X(7) activity was associated with the risk of losing asthma control (crude odds ratio, 11.0; 95% confidence interval, 1.1-106.4) even after adjustment for inhaled corticosteroids and rhinovirus (odds ratio, 15.0).A whole blood P2X(7) pore assay robustly identifies participants with loss-of-function genotypes. Using this assay as an epidemiologic tool, attenuated P2X(7) pore activity may be a novel biomarker of virus-induced loss of asthma control.
Meta-analysis: Sequential Therapy Appears Superior to Standard Therapy for Helicobacter pylori Infection in Patients Naive to Treatment
Authors: Nadim S. Jafri
Journal: Annals of Internal Medicine (2008)

Background: Standard proton-pump inhibitor–based therapy for Helicobacter pylori infection fails in up to one quarter of patients. Sequential therapy may be more efficacious. Purpose: To compare sequential therapy with standard triple therapy for H. pylori infection. Data Sources: MEDLINE, EMBASE (1981 to October 2007), the Cochrane Central Register of Controlled Trials, and Google Scholar. PubMed and Ovid were the search engines used. Study Selection: Randomized, controlled trials (RCTs) comparing sequential and standard triple therapies in treatment-naive patients with documented H. pylori infection. Data Extraction: 3 reviewers independently assessed trial eligibility and quality and extracted data on eradication. Data Synthesis: The crude rates of H. pylori eradication in 10 RCTs involving 2747 patients were 93.4% (95% CI, 91.3% to 95.5%) for sequential therapy (n = 1363) and 76.9% (CI, 71.0% to 82.8%) for standard triple therapy (n = 1384) (relative risk reduction, 71% [CI, 64% to 77%]; absolute risk reduction, 16 percentage points [CI, 14 to 19 percentage points]). The median rates of adherence were 97.4% (range, 90.0% to 98.9%) for sequential therapy and 96.8% (range, 93.0% to 100%) for standard therapy. Sequential therapy appeared superior in prespecified sensitivity (subgroup) analyses stratified by trial quality; smoking status; diagnosis (ulcer disease or nonulcer dyspepsia); resistance to clarithromycin, imidazoles, or both; duration of triple therapy; and method of diagnosis. Both treatments had similar side effect profiles. Limitations: Only 1 study was double-blinded. Most patients were from Italy. There was clear evidence of publication bias. Conclusion: Sequential therapy appears superior to standard triple therapy for eradication of H. pylori infection. If RCTs in other countries confirm these findings, 10-day sequential therapy could become a standard treatment for H. pylori infection in treatment-naive patients.
Hypoxia does not alter angiotensin converting enzyme activity in hamster pulmonary microvessels.
Authors: J M Shepard, W L Joyner, J P Gilmore
Journal: Circulation Research (1987)

Studies were initiated to investigate the effects of hypoxia on the conversion of angiotensin I (AI) to angiotensin II (AII) in microvessels of the lung. Using the technique of allografting neonatal lung tissue into the cheek pouch of normal hamsters, the microvessels of the lung, pulmonary arterioles, and venules could be visualized and manipulated by direct in vivo microscopy. The microvessels of the lung were studied 7-10 days after allografting by anesthetizing the hamster with pentobarbital (6.0 mg/100 g body weight i.p.) and then preparing the lung tissue for observation. The tissue was suffused with a Ringer's bicarbonate solution bubbled with a normal (20% O2-5% CO2-75% N2) or a low (95% N2-5% CO2) oxygen mixture. After equilibration, a pulmonary arteriole or venule was selected for observation, and the vessel geometry was recorded. Then, a micropipette containing either AI or AII was positioned alongside the vessel, and the agent was delivered continuously for 2 minutes. Lumen diameter was recorded continually for 8-10 minutes. This procedure was repeated until both angiotensins were tested on pulmonary arterioles and venules under conditions of a normal and low oxygen environment. This protocol was repeated on cheek pouch microvessels that did not contain pulmonary allografts. Both AI and AII produced rapid decreases in the lumen diameters of all microvessels tested. This vasoconstriction was greater for AII, and the oxygen environment did not alter the response. Conversion of AI to AII was not altered by the oxygen environment, and the relative conversion was similar in the microvessels of the lung and cheek pouch.(ABSTRACT TRUNCATED AT 250 WORDS)
Mobilization of long-term reconstituting hematopoietic stem cells in mice by recombinant human interleukin 7.
Authors: K J Grzegorzewski, K L Komschlies, S E Jacobsen, F W Ruscetti, J R Keller, R H Wiltrout
Journal: The Journal of Experimental Medicine (1995)

Administration of recombinant human interleukin 7 (rh)IL-7 to mice has been reported by our group to increase the exportation of myeloid progenitors (colony-forming unit [CFU]-c and CFU-granulocyte erythroid megakarocyte macrophage) from the bone marrow to peripheral organs (blood, spleen[s], and liver). We now report that IL-7 also stimulates a sixfold increase in the number of more primitive CFU-S day 8 (CFU-S8) and day 12 (CFU-S12) in the peripheral blood leukocytes (PBL) of mice treated with rhIL-7 for 7 d. Moreover, > 90% of lethally irradiated recipient mice that received PBL from rhIL-7-treated donor mice have survived for > 6 mo whereas none of the recipient mice that received an equal number of PBL from diluent-treated donors survived. Flow cytometry analysis at 3 and 6 mo after transplantation revealed complete trilineage (T, B, and myelomonocytic cell) repopulation of bone marrow, thymus, and spleen by blood-borne stem/progenitor cells obtained from rhIL-7-treated donor mice. Thus, IL-7 may prove valuable for mobilizing pluripotent stem cells with long-term repopulating activity from the bone marrow to the peripheral blood for the purpose of gene modification and/or autologous or allogeneic stem cell transplantation.
Structural and Functional Characterization of Dog Heart Microsomes
Authors: Petrus J. Pretorius, W. Gerhard Pohl, Charles S. Smithen, Giuseppe Inesi
Journal: Circulation Research (1969)

Several procedures for the preparation of microsomes from heart tissue were compared. Sucrose was found the most effective addition to preserve the activity of the sarcoplasmic reticulum vesicles. Electron microscopy of sectioned pellets shows uniform vesicles, but negative staining of microsomal suspensions allows recognition of mitochondrial fragments, which are found in cardiac microsomal fractions in greater amounts than in skeletal muscle preparations. The quantity of mitochondrial contaminations in different fractions was estimated by measuring enzymatic activities. A comparison of Ca 2+ accumulation, Ca 2+ efflux, and ATPase activity shows identical features in preparations from the heart and from skeletal muscle, although the specific activity is approximately ten times lower in those from the heart. The apparent affinity of sarcoplasmic reticulum for Ca 2+ in vitro justifies the assumption that sarcoplasmic reticulum lowers the intracellular Ca 2+ concentration in the in-vivo heart below the level required for contraction. However, in a weight unit of fresh tissue, the ratio between the maximal Ca 2+ accumulated by SR and the amount of contractile protein is much lower in the heart than in skeletal muscle. Caffeine and, more markedly, propranolol and tetracaine increase efflux of accumulated Ca 2+ and thereby reduce net uptake by fragmented sarcoplasmic reticulum. Isopropylmethoxamine is not effective at millimolar concentrations.
Survival and Disease Progression in Essential Thrombocythemia Are Significantly Influenced by Accurate Morphologic Diagnosis: An International Study
Authors: Tiziano Barbui, Juergen Thiele, Francesco Passamonti, Elisa Rumi, Emanuela Boveri, Marco Ruggeri, Francesco Rodeghiero, Emanuele S.G. d'Amore, Maria Luigia Randi, Irene Bertozzi, Filippo Marino, Alessandro M. Vannucchi, Elisabetta Antonioli, Valentina Carrai, Heinz Gisslinger, Veronika Buxhofer-Ausch, Leonhard Müllauer, Alessandra Carobbio, Andrea Gianatti, Naseema Gangat, Curtis A. Hanson, Ayalew Tefferi
Journal: Journal of Clinical Oncology (2011)

Purpose The WHO diagnostic criteria underscore the role of bone marrow (BM) morphology in distinguishing essential thrombocythemia (ET) from early/prefibrotic primary myelofibrosis (PMF). This study examined the clinical relevance of such a distinction. Methods Representatives from seven international centers of excellence for myeloproliferative neoplasms convened to create a clinicopathologic database of patients previously diagnosed as having ET (N = 1,104). Study eligibility criteria included availability of treatment-naive BM specimens obtained within 1 year of diagnosis. All bone marrows subsequently underwent a central re-review. Results Diagnosis was confirmed as ET in 891 patients (81%) and was revised to early/prefibrotic PMF in 180 (16%); 33 patients were not evaluable. In early/prefibrotic PMF compared with ET, the 10-year survival rates (76% and 89%, respectively) and 15-year survival rates (59% and 80%, respectively), leukemic transformation rates at 10 years (5.8% and 0.7%, respectively) and 15 years (11.7% and 2.1%, respectively), and rates of progression to overt myelofibrosis at 10 years (12.3% and 0.8%, respectively) and 15 years (16.9% and 9.3%) were significantly worse. The respective death, leukemia, and overt myelofibrosis incidence rates per 100 patient-years for early/prefibrotic PMF compared with ET were 2.7% and 1.3% (relative risk [RR], 2.1; P &lt; .001), 0.6% and 0.1% (RR, 5.2; P = .001), and 1% and 0.5% (RR, 2.0; P = .04). Multivariable analysis confirmed these findings and also identified age older than 60 years (hazard ratio [HR], 6.7), leukocyte count greater than 11 × 10 9 /L (HR, 2.01), anemia (HR, 2.95), and thrombosis history (HR, 2.81) as additional risk factors for survival. Thrombosis and JAK2V617F incidence rates were similar between the two groups. Survival in ET was similar to the sex- and age-standardized European population. Conclusion This study validates the clinical relevance of strict adherence to WHO criteria in the diagnosis of ET and provides important information on survival, disease complication rates, and prognostic factors in strictly WHO-defined ET and early/prefibrotic PMF.
Alcohol drinking and risk of renal cell carcinoma: results of a meta-analysis
Authors: R. Bellocco, E. Pasquali, M. Rota, V. Bagnardi, I. Tramacere, L. Scotti, C. Pelucchi, P. Boffetta, G. Corrao, C. La Vecchia
Journal: Annals of Oncology (2012)
Effects of Plasmid-Based Stat3-Specific Short Hairpin RNA and GRIM-19 on PC-3M Tumor Cell Growth
Authors: Ling Zhang, Lifang Gao, Yang Li, Guimiao Lin, Yueting Shao, Kun Ji, Hao Yu, Jiadi Hu, Dhananjaya V. Kalvakolanu, Dennis J. Kopecko, Xuejian Zhao, De-Qi Xu
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Persistent activation of signal transducers and activators of transcription 3 (Stat3) and its overexpression contribute to the progression and metastasis of several different tumor types. For this reason, Stat3 is a reasonable target for RNA interference–mediated growth inhibition. Blockade of Stat3 using specific short hairpin RNAs (shRNA) can significantly reduce prostate tumor growth in mice. However, RNA interference does not fully ablate target gene expression in vivo, owing to the idiosyncrasies associated with shRNAs and their targets. To enhance the therapeutic efficacy of Stat3-specific shRNA, we applied a combination treatment involving gene associated with retinoid-IFN–induced mortality 19 (GRIM-19), another inhibitor of STAT3, along with shRNA. Experimental Design: The coding sequences for GRIM-19, a cellular STAT3-specific inhibitor, and Stat3-specific shRNAs were used to create a dual expression plasmid vector and used for prostate cancer therapy in vitro and in mouse xenograft models in vivo. Results: The coexpressed Stat3-specific shRNA and GRIM-19 synergistically and more effectively suppressed prostate tumor growth and metastases when compared with treatment with either single agent alone. Conclusion: The simultaneous use of two specific, but mechanistically different, inhibitors of STAT3 activity exerts enhanced antitumor effects.
Patient preferences for treatment of rheumatoid arthritis
Authors: L Fraenkel
Journal: Annals of the Rheumatic Diseases (2004)

<b>Objective:</b> To elicit treatment preferences of patients with rheumatoid arthritis (RA) for disease modifying antirheumatic drugs (DMARDs) with varying risk profiles. <b>Methods:</b> Patient values for 16 DMARD characteristics were ascertained using published data about side effects, effectiveness, and cost. Patient preferences were determined by Adaptive Conjoint Analysis, an interactive computer program that predicts preferences by asking patients to make trade-offs between specific treatment characteristics. Simulations were run to derive preferences for four drugs: methotrexate, gold, leflunomide, and etanercept, under different risk-benefit scenarios. Infliximab was not included because it is given with methotrexate, and we did not include preferences for combination therapy. Based on each patient's expressed preferences, and the characteristics of the treatments available at the time of the study, the option that best fitted each patient's perspective was identified. <b>Results:</b> 120 patients (mean age 70 years) were interviewed. For the base case scenario (which assumed the maximum benefits reported in the literature, a low probability of adverse effects, and low equal monthly "co-pays" (out of pocket costs)), 95% of the respondents preferred etanercept over the other treatment options. When all four options were described as being equally effective, 88% continued to prefer etanercept owing to its safer short term adverse effect profile. Increasing etanercept's co-pay to $30.00 decreased the percentage of patients preferring this option to 80%. <b>Conclusions:</b> In this study, older patients with RA, when asked to consider trade-offs between specific risk and benefits, preferred etanercept over other treatment options. Preference for etanercept is explained by older patients' risk aversion for drug toxicity.
Cross-Presentation, Dendritic Cells, Tolerance and Immunity
Authors: William R. Heath, Francis R. Carbone
Journal: Annual Review of Immunology (2001)

This review examines the role of cross-presentation in tolerance and immunity. We discuss (a) the antigenic requirements for cross-presentation, (b) the phenotype of the antigen presenting cell (APC), (c) the cellular interactions and molecular signals involved in cross-priming, and (d) the factors that direct the immune system toward tolerance or immunity. A large part of this review is dedicated to summarizing our current knowledge of the cross-presenting APC.
Effect of heme arginate administration on blood pressure in spontaneously hypertensive rats.
Authors: R D Levere, P Martasek, B Escalante, M L Schwartzman, N G Abraham
Journal: Journal of Clinical Investigation (1990)

Cytochrome P450 content and activities are increased in the kidneys of spontaneously hypertensive rats (SHR) as compared with those of normotensive, Wistar-Kyoto (WKY), control rats during the period of rapid elevation of blood pressure. We studied the effect of heme arginate, a potent inducer of heme oxygenase (EC 1.14.99.3), on microsomal cytochrome P450 levels and activities and blood pressure in SHR at 7 wk of age. Administration of heme arginate (15 mg/kg body weight for 4 d) resulted in a marked decrease in blood pressure from 156.3 +/- 4.7 to 129.8 +/- 4.5 mm Hg (P less than 0.001), whereas blood pressure in SHR receiving the vehicle control was not affected. The blood pressure of age-matched WKY was not affected by heme arginate. Heme oxygenase activity increased in both hepatic and renal microsomes of SHR and WKY by two- to four-fold after treatment with heme arginate. Maximal increase of heme oxygenase mRNA occurred 5-7 h after the last injection of heme arginate and returned to control levels after 24 h. The increase in heme oxygenase activity was associated with a parallel decrease in cytochrome P450 content and in the activity of cytochrome P450 omega/omega-1 arachidonate hydroxylases in kidneys of SHR. It is postulated that heme arginate treatment resulted in induction of heme oxygenase which consequently led to a diminution of cytochrome P450, especially the arachidonate omega/omega-1 hydroxylases leading to a marked decrease in 19-hydroxyeicosatetraenoic acid (HETE) and 20-HETE. The effect of heme arginate on blood pressure may be mediated via these biochemical events inasmuch as both 19-HETE and 20-HETE produced by the kidney may promote hypertension by causing vasoconstriction and sodium retention.
Kangaroo Mother Care, an example to follow from developing countries
Authors: Juan Gabriel Ruiz-Peláez, Nathalie Charpak, Luis Gabriel Cuervo
Journal: BMJ (2004)

<i>Caring for low birthweight infants imposes a heavy burden on poor countries. An effective healthcare technique developed in 1978 may offer a solution to this problem and additionally be of use in wealthy countries too</i>
The lowdown on sugar highs
Authors: Hema Bashyam
Journal: The Journal of Experimental Medicine (2008)

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Cells exposed to high glucose (HG) levels overexpress NF-κB due to histone modifications of the NF-κB promoter by the enzyme Set7. Short-lived sugar highs might give a quick energy boost, but according to El-Osta et al. (page 

[2409][2]), they also leave a lasting bad
The Prognostic Significance of Plasma Interleukin-6 Levels in Patients with Metastatic Hormone-Refractory Prostate Cancer: Results from Cancer and Leukemia Group B 9480
Authors: Daniel J. George, Susan Halabi, Timothy F. Shepard, Ben Sanford, Nicholas J. Vogelzang, Eric J. Small, Philip W. Kantoff
Journal: Clinical Cancer Research (2005)

Interleukin-6 signaling can activate androgen receptor in a ligand-independent manner and may play an important functional role in hormone-refractory prostate cancer (HRCaP) progression and patient survival. Plasma and serum IL-6 levels have been associated with prostate cancer progression in several small studies. In order to evaluate its prognostic significance in metastatic HRCaP patients, we measured IL-6 in plasma collected at baseline from patients in a large cooperative group study [Cancer and Leukemia Group B 9480 (CALGB 9480)].191 patients entered on CALGB 9480 had pretreatment plasma collected and centrally stored. Using a human IL-6 immunoassay, quantitative levels of IL-6 were measured in duplicate on 300 muL samples. The proportional hazard model was used to assess the prognostic significance of IL-6 in predicting overall survival.Median IL-6 level for the cohort of 191 patients was 4.80 pg/mL. Survival time among patients with IL-6 levels less than or equal to the median was 19 months (95% CI, 17-22) compared with 11 (95% CI, 8-14) months for patients above the median (P = 0.0004). In multivariate analysis, adjusting on performance status, lactate dehydrogenase, and prostate-specific antigen level, the hazard ratio was 1.38 (95% CI, 1.01-1.89; P = 0.043) using the median level as a cut point. Furthermore, a cut point of 13.31 pg/mL revealed robust prognostic significance with a hazard ratio of 2.02 (95% CI, 1.36-2.98; P = 0.0005).Plasma IL-6 level has prognostic significance in patients with metastatic HRCaP from CALGB 9480. These findings support using IL-6 levels in prognostic models and support the rationale for IL-6-targeted therapy in patients with HRCaP.