tbuckley/cabot-search huggingface dataset:
Peculiarities of sex hormonal status and incidence of osteoporosis in perimenopausal asthmatic women
Authors: Tetyana Chursinova, Tetyana Pertseva, Valeriia Dmytrychenko
Journal: European Respiratory Journal (2013)

The aim  of the present research is studying the level of sex, gonadotropic hormones and incidence of osteoporosis in perimenopausal women with bronchial asthma (BA) depending on the severity of asthma.   Methods.  Overall 120 asthmatic women aged from 42 to 55 years (mean age 50,25±0,38 years) were assessed. Patients were divided into four groups: I gr. – 30 patients with intermittent asthma, II gr. – 28 patients with mild persistent asthma, III gr. – 32 patients with moderate persistent asthma, IV gr. – 30 patients with severe persistent asthma. Control gr.: 28 perimenopausal women without BA (mean age 50,82±0,67 years).  Physical examination, serum levels of follicle-stimulating (FSH) and luteinizing hormones (LH), estradiole, progesterone were performed. Osteoporosis was detected by ultrasound bone densitometry (T-score).   Results.  There were not authentic differences in levels of sex and gonadotropic hormones in patients of I gr. and II gr. compared with control gr. Patients of III gr. had a tendency to increase of estradiole level. Patient of IV gr. had authentically lower concentration of FSH (p=0,005), estradiole (p=0,001), and progesterone (p=0,001). Patients with severe BA have the authentically highest incidence of osteoporosis – 46,67 % compared with women of the control gr. – 14,29 % (p=0,006), patients with intermittent BA – 20 %, mild and moderate BA – 17,85 % and 31,25 % respectively. We received positive correlation between estradiole level and T-score (r=0,44, p=0,001).   Conclusion.  Perimenopausal women with severe asthma have a necessity of early detection of sex hormones disorders, correction of hormonal status to prevent osteoporosis.
THE PREDICTIVE VALUE OF TRADITIONAL RISK FACTORS IN THE ASSESSMENT OF CORONARY ARTERY DISEASE BURDEN IN SOUTH ASIANS VS NON SOUTH ASIANS: A CORONARY COMPUTED TOMOGRAPHY ANGIOGRAPHY STUDY
Authors: Amir Ahmadi, Mark Chandy, Gilat Grunau, Reza Faraji, Saman Rezazadeh, Brett Heilbron, Krishnan Ramanathan, Carolyn M. Taylor, Jonathon Leipsic
Journal: Journal of the American College of Cardiology (2011)
Cost-Effectiveness of ADHD Treatments: Findings From the Multimodal Treatment Study of Children With ADHD
Authors: Peter S. Jensen, Joe Albert Garcia, Sherry Glied, Maura Crowe, Mike Foster, Michael Schlander, Stephen Hinshaw, Benedetto Vitiello, L. Eugene Arnold, Glen Elliott, Lily Hechtman, Jeffrey H. Newcorn, William E. Pelham, James Swanson, Karen Wells
Journal: American Journal of Psychiatry (2005)

Attention deficit hyperactivity disorder (ADHD) is a costly public health problem. To the authors' knowledge, this is the first study on the cost-effectiveness of the major forms of ADHD treatments used in NIMH's Multimodal Treatment Study of Children With ADHD (MTA Study).Five hundred seventy-nine children with ADHD, combined type, ages 7 to 9.9, were assigned to 14 months of medication management, behavioral treatment, both combined, or community care. Services were tallied throughout the study, including medication, health care visits, behavioral treatments, and rental costs. Provider specialty, total time, and number of visits with providers were used to calculate costs, adjusted to FY 2000 dollars with the consumer price index.Treatment costs varied fourfold, with medication management being the least expensive, followed by behavioral treatment, and then combined treatment. Lower costs of medication treatment were found in the community care group, reflecting the less intensive (and less effective) nature of community-delivered treatment. Medical management was more effective but more costly than community care and more cost-effective than combination treatment and behavioral treatment alone. Under some conditions, combination treatment (medical management and psychotherapy) were somewhat more cost-effective, as demonstrated by lower costs per additional child "normalized" among children with multiple comorbid disorders.Medical management treatment, although not as effective as combined medical management and behavioral treatment, is likely to be more cost-effective in routine treatment for children with ADHD, particularly those without comorbid disorders. For some children with comorbid disorders, it may be cost-effective to provide combination treatment.
Risk of first venous thromboembolism in pregnant women in hospital: population based cohort study from England
Authors: A. Abdul Sultan, J. West, L. J. Tata, K. M. Fleming, C. Nelson-Piercy, M. J. Grainge
Journal: BMJ (2013)

<b>Objective</b> To examine the potential for preventing venous thromboembolism during and after antepartum hospital admissions in pregnant women. <b>Design</b> Cohort study using linked primary (Clinical Practice Research Datalink) and secondary (Hospital Episode Statistics) care records. <b>Setting</b> Primary and secondary care centres, England. <b>Participants</b> 206 785 women aged 15-44 who had one or more pregnancies from1997 up to 2010. <b>Main outcome measure</b> Risk of first venous thromboembolism in pregnant women admitted to hospital for one or more days for reasons other than delivery or venous thromboembolism. Risk was assessed by calculating the absolute rate of venous thromboembolism and comparing these rates with those observed during follow-up time not associated with hospital admission using a Poisson regression model to estimate incidence rate ratios. <b>Results</b> Admission to hospital in pregnancy was associated with an increased risk of venous thromboembolism (absolute rate 1752/100 000 person years; incidence rate ratio 17.5, 95% confidence interval 7.69 to 40.0) compared with time outside hospital. The rate of venous thromboembolism was also high during the 28 days after discharge (absolute rate 676; 6.27, 3.74 to 10.5). The rate during and after admission combined was highest in the third trimester (961; 5.57, 3.32 to 9.34) and in those aged ≥35 years (1756; 21.7, 9.62 to 49.0). While the absolute rate in the combined period was highest for those with three or more days in hospital (1511; 12.2, 6.65 to 22.7), there was also a fourfold increase (558; 4.05, 2.23 to 7.38) in the risk of venous thromboembolism for those admitted to hospital for less than three days. <b>Conclusion</b> The overall risk of first venous thromboembolism in pregnant women increased during admissions to hospital not related to delivery, and remained significantly higher in the 28 days after discharge. During these periods need for thromboprophylaxis should receive careful consideration.
Abnormal rheology of oxygenated blood in sickle cell anemia
Authors: Shu Chien, Shunichi Usami, John F. Bertles
Journal: Journal of Clinical Investigation (1970)

The viscosity of oxygenated blood from patients with sickle cell anemia (Hb SS disease) was found to be abnormally increased, a property which contrasts with the well recognized viscous aberration produced by deoxygenation of Hb SS blood. Experiments designed to explain this finding led to considerations of deformation and aggregation, primary determinants of the rheologic behavior of erythrocytes as they traverse the microcirculation. Deformability of erythrocytes is in turn dependent upon internal viscosity (i.e. the state and concentration of hemoglobin in solution) and membrane flexibility. Definition of the contribution made by each of these properties to the abnormal viscosity of oxygenated Hb SS blood was made possible by analysis of viscosity measurements, made over a wide range of shear rates and cell concentrations, on Hb SS erythrocytes and normal erythrocytes suspended in Ringer's solution (where aggregation does not occur) and in plasma. Similar measurements were made on the two cell types separated by ultracentrifugation of Hb SS erythrocytes: high density erythrocytes composed of 50 to 70% irreversibly "sickled" cells (ISC) and low density erythrocytes composed of over 95% non-ISC. Under all experimental conditions (hematocrit, shear rate, and suspending medium) the viscosity of ISC exceeds that of normal erythrocytes. The viscosity of non-ISC is elevated only in the absence of aggregation and over intermediate ranges of hematocrit. Analyses of the data reveal (a) an elevated internal viscosity of ISC: (b) a reduced membrane flexibility of both ISC and non-ISC, particularly at low shear rates; and (c) a reduced tendency for aggregation displayed by both cell types. The abnormal viscosity of oxygenated Hb SS blood can be attributed to the altered rheology of ISC and, to a lesser extent, of non-ISC. These studies assign a role to the abnormal rheology of Hb SS erythrocytes in the pathogenesis of sickle cell anemia, even under conditions of complete oxygenation.
Nocturnal blood pressure during apnoeic and ventilatory periods in patients with obstructive sleep apnoea
Authors: Y Tun, S Okabe, W Hida, H Kurosawa, M Tabata, Y Kikuchi, K Shirato
Journal: European Respiratory Journal (1999)

The exact nature of asleep blood pressure in relation to awake blood pressure is still unclear in patients with obstructive sleep apnoea. This study aimed: 1) to investigate the asleep blood pressure in both apnoeic and ventilatory periods; 2) to determine the diurnal and nocturnal factors correlated with the changes in blood pressure from apnoea to ventilatory periods during sleep. Thirty-two patients, newly diagnosed as moderate to severe obstructive sleep apnoea with a standard nocturnal polysomnography, were enrolled. The blood pressure was monitored by using the noninvasive continuous monitoring method during polysomnographic study. The mean blood pressures in ventilatory periods during nonrapid eye movement (NREM) and rapid eye movement (REM) sleep were 117.5+/-17.9 mm Hg and 128.8+/-21.9 mm Hg, and those in apnoea periods were 94.5+/-15.4 mm Hg and 102.7+/-19.0 mm Hg. The average blood pressure during NREM sleep (103.0+/-16.1 mm Hg) was higher than the awake blood pressure (97.0+/-15.7 mm Hg). The blood pressure during REM sleep was greater than that during NREM sleep. The changes in the nocturnal blood pressure from apnoea to ventilatory periods were inversely correlated with the age and nocturnal mean nadir saturation. In conclusion, patients with obstructive sleep apnoea have higher asleep blood pressure than awake blood pressure.
Functional delivery of DNAzyme with iron oxide nanoparticles for hepatitis C virus gene knockdown
Authors: Soo-Ryoon Ryoo, Hongje Jang, Ki-Sun Kim, Bokhui Lee, Kyung Bo Kim, Young-Kwan Kim, Woon-Seok Yeo, Younghoon Lee, Dong-Eun Kim, Dal-Hee Min
Journal: Biomaterials (2011)
Gait-related intrinsic risk factors for patellofemoral pain in novice recreational runners
Authors: Y Thijs, D De Clercq, P Roosen, E Witvrouw
Journal: British Journal of Sports Medicine (2008)

To determine prospectively gait-related intrinsic risk factors for patellofemoral pain (PFP) in a population of novice recreational runners.Prospective cohort study.102 novice recreational runners (89 women) with no history of knee or lower leg complaints.The standing foot posture of the subjects was examined and plantar pressure measurements during running were collected. The subjects then participated in a 10-week "start to run" programme. During this period all sports injuries were registered by a sports medicine physician.The relationship between the standing foot posture and PFP was investigated and gait-related intrinsic risk factors for PFP were determined.The 17 runners who developed PFP exerted a significantly higher vertical peak force underneath the lateral heel and metatarsals 2 and 3. Logistic regression analysis showed that a significantly higher vertical peak force underneath the second metatarsal and shorter time to the vertical peak force underneath the lateral heel were predictors for PFP. No significant evidence was found for an association between an excessively pronated or supinated foot posture and the development of PFP.The findings suggest that an excessive impact shock during heel strike and at the propulsion phase of running may contribute to an increased risk of developing PFP. The hypothesis that persons at risk for PFP show an altered static foot posture in comparison with non-afflicted persons is not supported by the results of this study.
Effects of norepinephrine on the oxidative pentose phosphate pathway in the rat heart.
Authors: H G Zimmer, B Lankat-Buttgereit, C Kolbeck-Rühmkorff, T Nagano, W Zierhut
Journal: Circulation Research (1992)

To examine whether stimulation of alpha-adrenergic receptors may affect the oxidative pentose phosphate pathway (PPP) in the rat heart, norepinephrine (NE) and the alpha-adrenergic agonist norfenephrine were used. NE was administered as a continuous intravenous infusion in awake rats for 3 days. It stimulated the activity of cardiac glucose-6-phosphate dehydrogenase (G-6-PD), the first and regulating enzyme of the oxidative PPP, in a dose-dependent manner. With the highest dose (0.2 mg.kg-1.hr-1), there was also a time-dependent enhancement. The increase observed after 48 hours was attenuated partially by the beta-receptor blocker metoprolol and the alpha-receptor blocker prazosin. It was entirely abolished when both drugs were administered. Carvedilol, a beta-adrenergic blocker and vasodilator with alpha 1-blocking activity (0.5 mg.kg-1.hr-1), prevented the NE-induced increase in cardiac G-6-PD activity, in functional parameters (heart rate, left ventricular systolic pressure, and left ventricular dP/dtmax), and in the heart weight/body weight ratio. The alpha-adrenergic stimulator norfenephrine increased myocardial G-6-PD activity; prazosin prevented this stimulation. NE and norfenephrine also elevated the available pool of cardiac 5-phosphoribosyl-1-pyrophosphate. G-6-PD activity was enhanced in cardiac myocytes freshly isolated from the left ventricle of rats that had received NE infusion for 3 days (12.3 +/- 1.4 units/g protein) compared with control rats (1.5 +/- 0.4 units/g protein). The activity of 6-phosphogluconate dehydrogenase, one of the enzymes in the oxidative PPP, was elevated only moderately from 12.7 +/- 0.7 to 19.1 +/- 1.4 units/g protein. Combined alpha- and beta-receptor blockade with carvedilol attenuated these effects.(ABSTRACT TRUNCATED AT 250 WORDS)
Clinical Impact of Delaying Initiation of Adjuvant Chemotherapy in Patients With Breast Cancer
Authors: Debora de Melo Gagliato, Ana M. Gonzalez-Angulo, Xiudong Lei, Richard L. Theriault, Sharon H. Giordano, Vicente Valero, Gabriel N. Hortobagyi, Mariana Chavez-MacGregor
Journal: Journal of Clinical Oncology (2014)

For patients with breast cancer (BC), the optimal time to initiation of adjuvant chemotherapy (TTC) after definitive surgery is unknown. We evaluated the association between TTC and survival according to breast cancer subtype and stage at diagnosis.Women diagnosed with BC stages I to III between 1997 and 2011 who received adjuvant chemotherapy at our institution were included. Patients were categorized into three groups according to TTC: ≤ 30, 31 to 60, and ≥ 61 days. Survival outcomes were estimated and compared according to TTC and by BC subtype.Among the 6,827 patients included, the 5-year overall survival (OS), relapse-free survival (RFS), and distant RFS (DRFS) estimates were similar for the different TTC categories. Initiation of chemotherapy ≥ 61 days after surgery was associated with adverse outcomes among patients with stage II (DRFS: hazard ratio [HR], 1.20; 95% CI, 1.02 to 1.43) and stage III (OS: HR, 1.76; 95% CI, 1.26 to 2.46; RFS: HR, 1.34; 95% CI, 1.01 to 1.76; and DRFS: HR, 1.36; 95% CI, 1.02 to 1.80) BC. Patients with triple-negative BC (TNBC) tumors and those with human epidermal growth factor receptor 2 (HER2) -positive tumors treated with trastuzumab who started chemotherapy ≥ 61 days after surgery had worse survival (HR, 1.54; 95% CI, 1.09 to 2.18 and HR, 3.09; 95% CI, 1.49 to 6.39, respectively) compared with those who initiated treatment in the first 30 days after surgery.TTC influenced survival outcomes in the overall study cohort. This finding was particularly meaningful for patients with stage III BC, TNBC, and trastuzumab-treated HER2-positive tumors who experienced worse outcomes when chemotherapy was delayed. Our findings suggest that early initiation of chemotherapy should be granted for patients in these high-risk groups.
Targeted Inactivation of the IL-4 Receptor α Chain I4R Motif Promotes Allergic Airway Inflammation
Authors: Frank Blaeser, Paul J. Bryce, Nga Ho, Vidya Raman, Fatma Dedeoglu, Debra D. Donaldson, Raif S. Geha, Hans C. Oettgen, Talal A. Chatila
Journal: The Journal of Experimental Medicine (2003)

The insulin/interleukin-4 (IL-4) receptor (I4R) motif mediates the association of insulin receptor substrate (IRS)-2 with the interleukin-4 (IL-4)Rα chain and transduces mitogenic signals in response to IL-4. Its physiological functions were analyzed in mice with a germline point mutation that changed the motif's effector tyrosine residue into phenylalanine (Y500F). The Y500F mutation abrogated IRS-2 phosphorylation and impaired IL-4–induced CD4+ T lymphocyte proliferation but left unperturbed Stat6 activation, up-regulation of IL-4-responsive gene products, and Th cell differentiation under Th2 polarizing conditions. However, in vivo the Y500F mutation was associated with increased allergen-induced IgE production, airway responsiveness, tissue eosinophilia, and mucus production. These results define an important role for the I4R motif in regulating allergic inflammation.
β2-adrenoceptor blockage induces G1/S phase arrest and apoptosis in pancreatic cancer cells via Ras/Akt/NFκB pathway
Authors: Dong Zhang, Qingyong Ma, Zheng Wang, Min Zhang, Kun Guo, Fengfei Wang, Erxi Wu
Journal: Molecular Cancer (2011)

Abstract Background Smoking and stress, pancreatic cancer (PanCa) risk factors, stimulate nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and catecholamines production respectively. NNK and catecholamine bind the β-adrenoceptors and induce PanCa cell proliferation; and we have previously suggested that β-adrenergic antagonists may suppress proliferation and invasion and stimulate apoptosis in PanCa. To clarify the mechanism of apoptosis induced by β 2 -adrenergic antagonist, we hypothesize that blockage of the β 2 -adrenoceptor could induce G 1 /S phase arrest and apoptosis and Ras may be a key player in PanCa cells. Results The β 1 and β 2 -adrenoceptor proteins were detected on the cell surface of PanCa cells from pancreatic carcinoma specimen samples by immunohistochemistry. The β 2 -adrenergic antagonist ICI118,551 significantly induced G 1 /S phase arrest and apoptosis compared with the β 1 -adrenergic antagonist metoprolol, which was determined by the flow cytometry assay. β 2 -adrenergic antagonist therapy significantly suppressed the expression of extracellular signal-regulated kinase, Akt, Bcl-2, cyclin D1, and cyclin E and induced the activation of caspase-3, caspase-9 and Bax by Western blotting. Additionally, the β 2 -adrenergic antagonist reduced the activation of NFκB in vitro cultured PanCa cells. Conclusions The blockage of β 2 -adrenoceptor markedly induced PanCa cells to arrest at G 1 /S phase and consequently resulted in cell death, which is possibly due to that the blockage of β 2 -adrenoceptor inhibited NFκB, extracellular signal-regulated kinase, and Akt pathways. Therefore, their upstream molecule Ras may be a key factor in the β 2 -adrenoceptor antagonist induced G 1 /S phase arrest and apoptosis in PanCa cells. The new pathway discovered in this study may provide an effective therapeutic strategy for PanCa.
Krüppel-Like Factor-4 Transcriptionally Regulates VE-Cadherin Expression and Endothelial Barrier Function
Authors: Colleen E. Cowan, Erin E. Kohler, Tracey A. Dugan, M. Kamran Mirza, Asrar B. Malik, Kishore K. Wary
Journal: Circulation Research (2010)

Vascular endothelial (VE)-cadherin localized at adherens junctions (AJs) regulates endothelial barrier function. Because WNT (wingless) signaling-induced activation of the transcription factor Krüppel-like factor (KLF)4 may have an important role in mediating the expression of VE-cadherin and AJ integrity, we studied the function of KLF4 in regulating VE-cadherin expression and the control of endothelial barrier function.The goal of this study was to determine the transcriptional role of KLF4 in regulating VE-cadherin expression and endothelial barrier function.Expression analysis, microscopy, chromatin immunoprecipitation, electrophoretic mobility shift assays, and VE-cadherin-luciferase reporter experiments demonstrated that KLF4 interacted with specific domains of VE-cadherin promoter and regulated the expression of VE-cadherin at AJs. KLF4 knockdown disrupted the endothelial barrier, indicating that KLF4 is required for normal barrier function. In vivo studies in mice showed augmented lipopolysaccharide-induced lung injury and pulmonary edema following Klf4 depletion.Our data show the key role of KLF4 in the regulation of VE-cadherin expression at the level of the AJs and in the acquisition of VE-cadherin-mediated endothelial barrier function. Thus, KLF4 maintains the integrity of AJs and prevents vascular leakage in response to inflammatory stimuli.
Demethylation of the <b> <i>Synuclein</i> </b> γ Gene CpG Island in Primary Gastric Cancers and Gastric Cancer Cell Lines
Authors: Naoki Yanagawa, Gen Tamura, Teiichiro Honda, Makoto Endoh, Satoshi Nishizuka, Teiichi Motoyama
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Whereas synuclein γ (SNCG) gene expression is usually highly tissue-specific and restricted to the nervous system, SNCG is expressed in advanced-stage breast and ovarian cancers. When overexpressed, SNCG stimulates cancer cell proliferation and metastasis. It is thought that the molecular mechanism of CpG island demethylation may underlie aberrant SNCG expression. To determine whether aberrant SNCG expression and demethylation play a role in gastric carcinogenesis, we examined the expression and methylation status of SNCG in primary gastric cancers, gastric cancer cell lines, and non-neoplastic gastric mucosal tissues. Experimental Design: Ten gastric cancer cell lines, 105 primary gastric cancers, and 10 non-neoplastic gastric mucosal tissues were examined. SNCG expression and methylation status were examined by reverse transcription-PCR and bisulfite-single-strand conformational polymorphism followed by direct sequencing, respectively. The relationship between SNCG methylation status and various clinicopathological factors of the primary gastric cancers was then analyzed. Results: SNCG mRNA expression was observed in 5 of 10 cell lines. Analysis of cell lines positive for SNCG expression revealed that most of the SNCG CpGs were demethylated. SNCG mRNA was not expressed in the 10 non-neoplastic gastric mucosal tissues, although several CpGs were demethylated. Of the 105 primary gastric cancers, 40 (38.1%) showed apparent SNCG demethylation, similar to the result obtained using cell lines. SNCG demethylation was more frequent in primary gastric cancers positive for lymph node metastasis (51%; 26 of 51) than in cancers without lymph node involvement (26%; 14 of 54; P &amp;lt; 0.05), and also more common in stage II-IV (48%; 27 of 56) than in stage I (27%; 13 of 49) cancers (P &amp;lt; 0.05). Conclusions: Aberrant SNCG gene expression can occur via CpG island demethylation, and tends to occur during the more progressive stages of gastric carcinogenesis.