tbuckley/cabot-search huggingface dataset:
Phenotypic changes in rat and guinea pig coronary microvascular endothelium after culture: loss of nitric oxide synthase activity
Authors: D Lang
Journal: Cardiovascular Research (1999)

Objectives: Coronary microvascular endothelial cells (CMVEs) can modulate the contractile performance of the adjacent myocardium by the release of agents such as nitric oxide (NO). Most previous studies using CMVEs have been done in situ, in the intact organ. We set out to study possible differences in NO synthase (NOS) regulation between freshly isolated and cultured rat and guinea pig CMVEs. Methods: CMVEs were isolated from Wistar rats and Dunkin Hartley guinea pigs and then grown in culture for varying times. Fura-2 fluorescence was used to measure agonist-induced changes in CMVE intracellular calcium levels. Agonist-induced changes in CMVE cGMP levels were measured by commercial radioimmunoassay kit. Western blot analysis was used to measure endothelial, constitutive NOS (ecNOS) and soluble guanylate cyclase (sGC) protein levels. Reverse transcription, polymerase chain reactions and Southern blotting were used to measure ecNOS mRNA transcripts. Results: In both fresh (1 h post-isolation) and cultured (14 days with one passage) CMVEs of the rat and guinea pig, bradykinin (BK) and the calcium ionophore A23187 (both 1 μM) elicited significant (P<0.01) increases in the fura-2 340/380 fluorescence ratio. In cultured CMVEs, basal cGMP levels were unaffected by exposure to BK or A23187. Exposure to sodium nitroprusside (SNP) or atrial natriuretic peptide (ANP) (both 1 μM) induced significant (P<0.01) increases in cGMP in guinea pig cells, whereas in rat cells only ANP produced a significant (P<0.01) response. By contrast, freshly isolated CMVEs of both species had higher basal cGMP levels than cultured cells, and on exposure to BK and A23187, responded with significant (P<0.01) increases in cGMP. Moreover, exposure of both fresh rat and guinea pig CMVEs to SNP or ANP also resulted in significant (P<0.01) increases in cGMP. Western blot analysis demonstrated that ecNOS and sGC protein were lost from the rat CMVEs following culture. Furthermore, there was also a significant loss of ecNOS mRNA from the rat cells following culture. Conclusions: These data demonstrate that freshly isolated rat and guinea pig CMVEs possess ecNOS activity, and that this activity is downregulated following culture. At least for the rat, this effect would seem to lie at both the transcriptional and translational level. Furthermore, rat CMVEs have reduced activity of sGC following culture.
Production of IL12p70 and IL23 by monocyte-derived dendritic cells in children with inflammatory bowel disease
Authors: G M Damen, P van Lierop, L de Ruiter, J C Escher, R Donders, J N Samsom, E E Nieuwenhuis
Journal: Gut (2008)

Inflammatory bowel disease (IBD) patients represent a heterogeneous group of patients that may need novel classification beyond just Crohns’ disease (CD) and ulcerative colitis (UC). Notably, based on patient specifics such as genetics, disease location, immune responses and drug responsiveness, it seems likely that early-onset IBDs represents a specific disease entity.1 Consequently, various disease-associated effector T cells have been identified, probably generated under the control of cytokines that are produced by antigen-presenting cells. In their recent publication, Kugathsan et al demonstrated that the level of IL12β2 (interleukin 12 receptor) expression by mucosal T cells may be a major determinant during the initial manifestations of CD for the development of the typically associated mucosal Th1 cytokine profile.2 In this case, the presence of a specific T cell receptor correlated …
Megakaryocyte-targeted synthesis of the integrin β3-subunit results in the phenotypic correction of Glanzmann thrombasthenia
Authors: David A. Wilcox, John C. Olsen, Lori Ishizawa, Paul F. Bray, Deborah L. French, Douglas A. Steeber, William R. Bell, Michael Griffith, Gilbert C. White
Journal: Blood (2000)
JAPANESE B ENCEPHALITIS VIRUS: ITS DIFFERENTIATION FROM ST. LOUIS ENCEPHALITIS VIRUS AND RELATIONSHIP TO LOUPING ILL VIRUS
Authors: Leslie T. Webster
Journal: The Journal of Experimental Medicine (1938)

1. Japanese B encephalitis virus, obtained from Japanese investigators, has proved virulent for mice and monkeys, confirming the reports from Japan. It has also been found virulent for monkeys when instilled intranasally and for sheep when introduced intracerebrally or intranasally. 2. Japanese B encephalitis virus has been differentiated from St. Louis virus and found similar to louping ill virus according to its reactions in animal species. Serologically, however, it is distinct. 3. Japanese B encephalitis and its related group of primary virus encephalitides of man have been discussed with regard to their differentiation and mode of spread.
Diaphragmatic paralysis due to Lyme disease
Authors: JL Faul, S Ruoss, RL Doyle, PN Kao
Journal: European Respiratory Journal (1999)

Lyme disease is a tick-borne spirochaete infection which, in a proportion of patients, can lead to neuropathy. This article describes a case of diaphragmatic paralysis due to Lyme disease. A 39-yr-old male presented to the hospital because of an acute left facial palsy. Six weeks prior to admission he had developed a circular rash on his left flank during a camping holiday. He also complained of shortness of breath and arthralgia for 1 week. His chest radiograph demonstrated a raised right hemi-diaphragm. Diaphragmatic paralysis was confirmed by fluoroscopy (a positive sniff test). Serology revealed evidence of recent infection by Borrelia burgdorferi. On the basis of the patient's clinical presentation, a recent history of erythema migrans, and positive Lyme serology, a diagnosis of neuroborreliosis was made. He received oral doxycycline therapy (200 mg x day(-1)) for three weeks. Facial and diaphragmatic palsies resolved within eight weeks. On the basis of this case, a diagnosis of Lyme disease should be considered in patients from endemic regions with otherwise unexplained phrenic nerve palsy.
Access to Kidney Transplantation among Patients Insured by the United States Department of Veterans Affairs
Authors: John S. Gill, Syed Hussain, Caren Rose, Sundaram Hariharan, Marcello Tonelli
Journal: Journal of the American Society of Nephrology (2007)

Ensuring equal access to kidney transplantation is of paramount importance. Veterans that receive care from the Department of Veteran Affairs (VA) must complete a complex process to be placed on the transplant wait-list, and only four VA hospitals in the United States transplant kidneys. This unique system may cause VA patients to wait longer for kidney transplants than other patients. We compared the time to transplantation among ESRD patients insured by the VA to those insured by private insurance or Medicare/Medicaid. Of 7395 veterans studied, 9.3% received transplants, compared to 35,450 of 144,651 (24.5%) patients with private insurance and 36,150 of 357,345 (10.1%) patients with Medicare/Medicaid insurance (P < 0.0001). We found that both VA-insured and Medicare/Medicaid-insured patients were approximately 35% less likely to receive transplants than patients with private insurance (hazard ratio [HR] 0.65; 95% CI 0.60 to 0.70; P < 0.0001). Most of this difference was explained by the fact that VA patients were less likely to be placed on the wait-list (HR 0.71; 95% CI 0.67 to 0.76), but even listed VA patients received transplants less frequently than those insured privately (HR 0.89; 95% CI 0.82 to 0.96). Interestingly, VA patients with supplemental private insurance had the same likelihood of transplantation as non-VA patients with private insurance. We conclude that VA-insured patients are less likely to receive transplants than privately insured patients, and that further studies are needed to identify the reasons for this disparity.
Preoperative Plasma Endoglin Levels Predict Biochemical Progression After Radical Prostatectomy
Authors: Robert S. Svatek, Jose A. Karam, Claus G. Roehrborn, Pierre I. Karakiewicz, Kevin M. Slawin, Shahrokh F. Shariat
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Endoglin (CD105) is a transmembrane glycoprotein expressed by human vascular endothelial cells thought to play a pivotal role in endothelial cell proliferation. The aim of this study was to evaluate the association of preoperative plasma endoglin levels with established clinical and pathologic features of prostate cancer and disease progression after radical prostatectomy. Experimental Design: Preoperative plasma endoglin levels were measured in 425 patients who underwent radical prostatectomy for clinically localized prostate cancer using a commercially available ELISA assay. Multivariate logistic regression was used to test the association of plasma endoglin levels with biochemical progression after radical prostatectomy. Results: Median follow-up for patients alive at the time of analysis was 36.8 months (interquartile range, 44.1). Of 425 patients, 77 patients (18.1%) experienced biochemical progression after radical prostatectomy. Preoperative plasma endoglin levels were significantly elevated in patients with higher preoperative total serum prostate-specific antigen (P &amp;lt; 0.001) and adverse pathologic features. Preoperative plasma endoglin was an independent predictor of biochemical progression after surgery after adjusting for the effects of standard preoperative and postoperative features (P &amp;lt; 0.001 and P = 0.026, respectively). Conclusions: Preoperative plasma endoglin levels are associated with established features of advanced prostate cancer. More importantly, higher preoperative plasma endoglin levels are independent predictors of an increased risk of biochemical progression in patients treated with radical prostatectomy and bilateral pelvic lymphadenectomy.
IL-2 regulates FOXP3 expression in human CD4+CD25+ regulatory T cells through a STAT-dependent mechanism and induces the expansion of these cells in vivo
Authors: Emmanuel Zorn, Erik A. Nelson, Mehrdad Mohseni, Fabrice Porcheray, Haesook Kim, Despina Litsa, Roberto Bellucci, Elke Raderschall, Christine Canning, Robert J. Soiffer, David A. Frank, Jerome Ritz
Journal: Blood (2006)
A phase II study evaluating the efficacy and safety of AMG 102 (rilotumumab) in patients with recurrent glioblastoma
Authors: P. Y. Wen, D. Schiff, T. F. Cloughesy, J. J. Raizer, J. Laterra, M. Smitt, M. Wolf, K. S. Oliner, A. Anderson, M. Zhu, E. Loh, D. A. Reardon
Journal: Neuro-Oncology (2011)

This phase II study evaluated the efficacy and safety of AMG 102 (rilotumumab), a fully human monoclonal antibody against hepatocyte growth factor/scatter factor (HGF/SF), in patients with recurrent glioblastoma (GBM). Patients with histologically confirmed, measurable recurrent GBM or gliosarcoma (World Health Organization grade 4) and ≤3 relapses or prior systemic therapies received AMG 102 (10 or 20 mg/kg) by infusion every 2 weeks. The primary endpoint was best confirmed objective response rate (central assessment) per Macdonald criteria. Of the 61 patients who enrolled, 60 received AMG 102. Twenty-nine patients (48%) had previously received bevacizumab. There were no objective responses per central assessment, but 1 patient had an objective response per investigator assessment. Median overall survival (95% CI) in the 10- and 20-mg/kg cohorts was 6.5 months (4.1–9.8) and 5.4 months (3.4–11.4), respectively, and progression-free survival (PFS) per central assessment was 4.1 weeks (4.0–4.1) and 4.3 weeks (4.1–8.1), respectively. PFS was similar among patients who had previously received bevacizumab compared with bevacizumab-naive patients. The most common adverse events were fatigue (38%), headache (33%), and peripheral edema (23%). AMG 102 serum concentrations increased approximately dose-proportionally with 2-fold accumulation at steady state. Plasma total HGF/SF and soluble c-Met concentrations increased 12.05- and 1.12-fold, respectively, from baseline during AMG 102 treatment. AMG 102 monotherapy at doses up to 20 mg/kg was not associated with significant antitumor activity in heavily pretreated patients with recurrent GBM.
Internet-based tapering of oral corticosteroids in severe asthma: a pragmatic randomised controlled trial
Authors: S. Hashimoto, A. T. Brinke, A. C. Roldaan, I. H. van Veen, G. M. Moller, J. K. Sont, E. J. M. Weersink, J. S. van der Zee, G.-J. Braunstahl, A. H. Zwinderman, P. J. Sterk, E. H. Bel
Journal: Thorax (2011)

In patients with prednisone-dependent asthma the dose of oral corticosteroids should be adjusted to the lowest possible level to reduce long-term adverse effects. However, the optimal strategy for tapering oral corticosteroids is unknown.To investigate whether an internet-based management tool including home monitoring of symptoms, lung function and fraction of exhaled nitric oxide (FE(NO)) facilitates tapering of oral corticosteroids and leads to reduction of corticosteroid consumption without worsening asthma control or asthma-related quality of life.In a 6-month pragmatic randomised prospective multicentre study, 95 adults with prednisone-dependent asthma from six pulmonary outpatient clinics were allocated to two tapering strategies: according to conventional treatment (n=43) or guided by a novel internet-based monitoring system (internet strategy) (n=52). Primary outcomes were cumulative sparing of prednisone, asthma control and asthma-related quality of life. Secondary outcomes were forced expiratory volume in 1 s (FEV1), exacerbations, hospitalisations and patient's satisfaction with the tapering strategy.Median cumulative sparing of prednisone was 205 (25-75th percentile -221 to 777) mg in the internet strategy group compared with 0 (-497 to 282) mg in the conventional treatment group (p = 0.02). Changes in prednisone dose (mixed effect regression model) from baseline were -4.79 mg/day and +1.59 mg/day, respectively (p < 0.001). Asthma control, asthma-related quality of life, FEV1, exacerbations, hospitalisations and satisfaction with the strategy were not different between groups.An internet-based management tool including home monitoring of symptoms, lung function and FE(NO) in severe asthma is superior to conventional treatment in reducing total corticosteroid consumption without compromising asthma control or asthma-related quality of life. Clinical trial registration number Clinical trial registered with http://www.trialregister.nl (Netherlands Trial Register number 1146).
Effect of L-dopa with and without inhibition of extra cerebral dopa decarboxylase on gastric acid secretion and gastrin release in man.
Authors: R Caldara, C Barbieri, V Piepoli, M Borzio, E Masci
Journal: Gut (1985)

The present study was undertaken to investigate the possibility that central nervous system monoaminergic pathways may play a role in the control of gastric acid and gastrin secretion in man. Submaximal pentagastrin stimulated (0.25 micrograms/kg/h) gastric acid secretion, as well as basal gastrin concentrations were studied in two groups of subjects. The first group received oral administration of placebo and the catecholamine precursor L-dopa (500 mg); the second group was treated with placebo and the association of L-dopa (100 mg) plus carbidopa (35 mg) after pretreatment with carbidopa (50 mg every six hours for four doses), a schedule which is known to increase brain catecholamine concentrations. In comparison with placebo, stimulated gastric acid secretion was reduced by L-dopa alone, whereas was not modified by L-dopa plus carbidopa. Basal gastrin concentrations were increased after L-dopa and after L-dopa plus carbidopa. These data show that basal gastrin concentration is raised by central catecholamine augmentation; but gastric acid secretion seems to be influenced by changes of peripheral catecholamine concentrations. It is suggested that dopamine and perhaps noradrenaline, but not adrenaline, are important in these effects.
Genome-wide identification of novel expression signatures reveal distinct patterns and prevalence of binding motifs for p53, nuclear factor-κB and other signal transcription factors in head and neck squamous cell carcinoma
Authors: Bin Yan, Xinping Yang, Tin-Lap Lee, Jay Friedman, Jun Tang, Carter Van Waes, Zhong Chen
Journal: Genome biology (2007)

Differentially expressed gene profiles have previously been observed among pathologically defined cancers by microarray technologies, including head and neck squamous cell carcinomas (HNSCCs). However, the molecular expression signatures and transcriptional regulatory controls that underlie the heterogeneity in HNSCCs are not well defined. Genome-wide cDNA microarray profiling of ten HNSCC cell lines revealed novel gene expression signatures that distinguished cancer cell subsets associated with p53 status. Three major clusters of over-expressed genes (A to C) were defined through hierarchical clustering, Gene Ontology, and statistical modeling. The promoters of genes in these clusters exhibited different patterns and prevalence of transcription factor binding sites for p53, nuclear factor-κB (NF-κB), activator protein (AP)-1, signal transducer and activator of transcription (STAT)3 and early growth response (EGR)1, as compared with the frequency in vertebrate promoters. Cluster A genes involved in chromatin structure and function exhibited enrichment for p53 and decreased AP-1 binding sites, whereas clusters B and C, containing cytokine and antiapoptotic genes, exhibited a significant increase in prevalence of NF-κB binding sites. An increase in STAT3 and EGR1 binding sites was distributed among the over-expressed clusters. Novel regulatory modules containing p53 or NF-κB concomitant with other transcription factor binding motifs were identified, and experimental data supported the predicted transcriptional regulation and binding activity. The transcription factors p53, NF-κB, and AP-1 may be important determinants of the heterogeneous pattern of gene expression, whereas STAT3 and EGR1 may broadly enhance gene expression in HNSCCs. Defining these novel gene signatures and regulatory mechanisms will be important for establishing new molecular classifications and subtyping, which in turn will promote development of targeted therapeutics for HNSCC.
Changes in postjunctional alpha-adrenoceptors during postnatal growth in rabbit arteries.
Authors: F M Tayo, R D Bevan, J A Bevan
Journal: Circulation Research (1986)

The pharmacological characteristics of the postjunctional alpha-adrenoceptors of vascular smooth muscle were studied in ring segments of thoracic aorta, superior mesenteric, and central ear arteries of 4- and 8-week-old, and young adult (12- to 16-week-old) rabbits. Norepinephrine (alpha 1, alpha 2-agonist), phenylephrine (alpha 1-agonist), and UK 14,304-18 (alpha 1-agonist) caused a concentration-dependent contraction of all three arterial segments from 4- and 8-week-old animals. Norepinephrine and phenylephrine but not UK 14,304-18 contracted the young adult thoracic aorta and superior mesenteric artery, whereas all the agonists contracted the central ear artery. The effects of the alpha 1-adrenoceptor antagonists, prazosin and thymoxamine, and the alpha 2-adrenoceptor antagonists, rauwolscine and yohimbine, on these responses were studied. In the 4-week-old rabbits, responses to norepinephrine, phenylephrine, and UK 14,304-18 were reduced by all four antagonists with nominal pA2 values in the range of 7-8.5. The action of the antagonists was competitive. Between 4 and 8 weeks, there was a significant decrease in the pA2 values of rauwolscine against norepinephrine and UK 14,304-18 in the aorta and between rauwolscine and UK 14,304-18 on the superior mesenteric artery. The pA2 values of rauwolscine and yohimbine, but not prazosin and thymoxamine, were lower in the young adult compared with values from the 8-week-old rabbit. In the interpretation of these results, there are two possibilities.(ABSTRACT TRUNCATED AT 250 WORDS)
A Population-Based Study of Lung Cancer Incidence Trends by Histologic Type, 1974–81
Authors: Linda Dodds, M.S.
 3, Scott Davis, Ph.D., Lincoln Polissar, Ph.D.
Journal: JNCI Journal of the National Cancer Institute (1986)

All incident cases of microscopically confirmed lung cancer diagnosed between 1974 and 1981 in western Washington State were identified through the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute, Bethesda, MD. The incidence of lung cancer by histologic type was studied in relation to time, with age, sex, and stage of disease at diagnosis being taken into account. Overall and within each sex, the incidence of adenocarcinoma has increased significantly since 1974. The rate of increase has been higher among females (86% increase) than among males (54% increase), with most of the increase in both sexes being among those over age 65 years with distant or unstaged disease at diagnosis. Similar patterns were not observed for squamous cell carcinoma. The potential effects of changes in diagnostic and pathology practice during the study period in producing these results were explored, and etiologic implications of the observed increase in adenocarcinoma were discussed.
Effects of Pioglitazone on Endothelial Function, Insulin Sensitivity, and Glucose Control in Subjects With Coronary Artery Disease and New-Onset Type 2 Diabetes
Authors: H. Sourij
Journal: Diabetes Care (2006)

OBJECTIVE—About one of five patients with coronary artery disease (CAD) suffers from previously unknown, predominantly postprandial type 2 diabetes. In the process of atherogenesis and the subsequent increased cardiovascular mortality of diabetic patients, endothelial dysfunction is suspected to play an important role, and it is observed in diabetic as well as insulin-resistant states. Thus, the aim of our study was to investigate the effect of pioglitazone on endothelial dysfunction, insulin sensitivity, and glucose control in newly detected type 2 diabetic patients with CAD.
Serum Iron Levels and the Risk of Parkinson Disease: A Mendelian Randomization Study
Authors: Irene Pichler, Fabiola Del Greco M., Martin Gögele, Christina M. Lill, Lars Bertram, Chuong B. Do, Nicholas Eriksson, Tatiana Foroud, Richard H. Myers, Michael Nalls, Margaux F. Keller, Beben Benyamin, John B. Whitfield, Peter P. Pramstaller, Andrew A. Hicks, John R. Thompson, Cosetta Minelli
Journal: PLoS Medicine (2013)

Although levels of iron are known to be increased in the brains of patients with Parkinson disease (PD), epidemiological evidence on a possible effect of iron blood levels on PD risk is inconclusive, with effects reported in opposite directions. Epidemiological studies suffer from problems of confounding and reverse causation, and mendelian randomization (MR) represents an alternative approach to provide unconfounded estimates of the effects of biomarkers on disease. We performed a MR study where genes known to modify iron levels were used as instruments to estimate the effect of iron on PD risk, based on estimates of the genetic effects on both iron and PD obtained from the largest sample meta-analyzed to date.We used as instrumental variables three genetic variants influencing iron levels, HFE rs1800562, HFE rs1799945, and TMPRSS6 rs855791. Estimates of their effect on serum iron were based on a recent genome-wide meta-analysis of 21,567 individuals, while estimates of their effect on PD risk were obtained through meta-analysis of genome-wide and candidate gene studies with 20,809 PD cases and 88,892 controls. Separate MR estimates of the effect of iron on PD were obtained for each variant and pooled by meta-analysis. We investigated heterogeneity across the three estimates as an indication of possible pleiotropy and found no evidence of it. The combined MR estimate showed a statistically significant protective effect of iron, with a relative risk reduction for PD of 3% (95% CI 1%-6%; p = 0.001) per 10 µg/dl increase in serum iron.Our study suggests that increased iron levels are causally associated with a decreased risk of developing PD. Further studies are needed to understand the pathophysiological mechanism of action of serum iron on PD risk before recommendations can be made.