tbuckley/cabot-search huggingface dataset:
Mono-L-arginine-containing compounds dilate piglet pial arterioles via an endothelium-derived relaxing factor-like substance.
Authors: D W Busija, C W Leffler, L C Wagerle
Journal: Circulation Research (1990)

We determined the effects of mono-L-arginine-containing compounds on pial arterioles of anesthetized piglets. A closed cranial window was implanted, and the diameter of one pial arteriole was determined by intravital microscopy. Diameter was determined during application of artificial cerebrospinal fluid containing no drugs and during application of 10(-5), 10(-4), 10(-3), and 10(-2) M L-arginine (ARG), L-arginine ethyl ester (AEE), N alpha-benzoyl-L-arginine (NBA), N alpha-benzoyl-L-arginine ester ethyl (BAEE), and L-citrulline (CIT). Initial diameters were 100-200 microns. All of these compounds dilated arterioles, but the threshold concentration needed to elicit dilation varied: 10(-5) M for NBA (n = 5), 10(-3) M for AEE (n = 9) and BAEE (n = 6), and 10(-2) M for ARG (n = 6) and CIT (n = 4). Maximal responses were 15 +/- 8% for CIT, 17 +/- 4% for ARG, 19 +/- 8% for BAEE, 28 +/- 5% for NBA, and 27 +/- 6% for AEE. Indomethacin pretreatment (5 mg/kg i.v.) did not change arteriolar responses to AEE, NBA, and BAEE. However, coadministration of methylene blue (0.5 x 10(-4) M or 0.5 x 10(-3) M) abolished dilation to 10(-3) M AEE or BAEE and attenuated dilation to 10(-5) M NBA. In addition, coadministration of hemoglobin (0.4 x 10(-4) M) abolished dilation to AEE, BAEE, or NBA. Last, intravenous (5 mg/kg) and coadministration (10(-3) M) of NG-methyl-L-arginine blocked dilation to NBA or AEE. We conclude that mono-L-arginine-containing compounds produce pial arteriolar dilation in piglets, possibly involving an endothelium-derived relaxing factor.
Antiviral CD4+ memory T cells are IL-15 dependent
Authors: Jared F. Purton, Joyce T. Tan, Mark P. Rubinstein, David M. Kim, Jonathan Sprent, Charles D. Surh
Journal: The Journal of Experimental Medicine (2007)

Survival and intermittent proliferation of memory CD4+ and CD8+ T cells appear to be controlled by different homeostatic mechanisms. In particular, contact with interleukin (IL)-15 has a decisive influence on memory CD8+ cells, but not memory CD4+ cells. Past studies of memory CD4+ cells have relied heavily on the use of naturally occurring memory phenotype (MP) cells as a surrogate for antigen (Ag)-specific memory cells. However, we show here that MP CD4+ cells contain a prominent subset of rapidly proliferating major histocompatibility complex (MHC) II–dependent cells. In contrast, Ag-specific memory CD4 cells have a slow turnover rate and are MHC II independent. In irradiated hosts, these latter cells ignore IL-15 and expand in response to the elevated levels of IL-7 in the lymphopenic hosts. In contrast, in normal nonlymphopenic hosts where IL-7 levels are low, memory CD4 cells are heavily dependent on IL-15. Significantly, memory CD4+ responsiveness to endogenous IL-15 reflects marked competition from other cells, especially CD8+ and natural killer cells, and increases considerably after removal of these cells. Therefore, under normal physiological conditions, homeostasis of CD8+ and CD4+ memory cells is quite similar and involves IL-15 and IL-7.
Sports injury prevention in your pocket?! Prevention apps assessed against the available scientific evidence: a review
Authors: Daan M van Mechelen, Willem van Mechelen, Evert A L M Verhagen
Journal: British Journal of Sports Medicine (2013)

Background High costs and personal burden follow sports and physical activity-related injuries (SPRI). The last decades’ knowledge on how to prevent SPRIs has grown. Past years’ eHealth is emerging and mobile applications (apps) helping to prevent SPRIs are appearing. Aim To review the content of iPhone and iPad apps containing a claim to prevent sports and physical activity-related injuries and to appraise this claim against best available scientific evidence. Methods The US iTunes App Store was searched using the keywords ‘injury’, ‘prevention’ and ‘rehabilitation’. Apps within the categories ‘health &amp; fitness’, ‘sports’ and ‘medical’ containing a preventive claim in the app name, description or screenshots were included. Claims were extracted and a search for best available evidence was performed. Results Eighteen apps met our inclusion criteria. Four of these apps contained claims for which evidence was available: three apps covered ankle sprains and provided information on taping or neuromuscular training. Of these three apps, one app also provided information on prevention of dental injury with mouth guards. One app provided a routine to prevent anterior cruciate ligament injury. The main focus of the five apps was running injury prevention; for their content evidence of absence of efficacy was found. For nine apps no evidence supporting their content was found. Conclusions f 18 apps included, only four contained claims that could be supported by available literature and five apps contained false claims. This lack of scientifically sound apps provides an opportunity for caretakers to develop apps with evidence-based claims to prevent SPRIs.
Oncogenic Targets, Magnitude of Benefit, and Market Pricing of Antineoplastic Drugs
Authors: Eitan Amir, Bostjan Seruga, Joaquin Martinez-Lopez, Ryan Kwong, Atanasio Pandiella, Ian F. Tannock, Alberto Ocaña
Journal: Journal of Clinical Oncology (2011)

Purpose The relationship between market pricing of new anticancer drugs and the magnitude of clinical benefit caused by them has not been reported. Patients and Methods Randomized clinical trials (RCTs) that evaluated approved new agents for solid tumors by the US Food and Drug administration since the year 2000 were assessed. Hazard ratios (HRs) and 95% CIs were extracted for time-to-event end points described for each RCT. HRs were pooled for three groups: agents directed against a specific molecular target, for which the target population is selected by a biomarker (group A); less specific biologic targeted agents (group B); and chemotherapeutic agents (group C). Monthly market prices of these different drugs were compared. Results For overall survival (OS), the pooled HR was 0.69 (95% CI, 0.59 to 0.81) for group A (six drugs, six trials); it was 0.78 (95% CI, 0.74 to 0.83) for group B (seven drugs, 14 trials); and it was 0.84 (95% CI, 0.79 to 0.90) for group C (eight drugs, 12 trials). For progression-free survival (PFS), the pooled HR was 0.42 (95% CI, 0.36 to 0.49) for group A (six drugs, seven trials); it was 0.57 (95% CI, 0.51 to 0.64) for group B (seven drugs, 14 trials); and it was 0.75 (95% CI, 0.66 to 0.85) for group C (six drugs, 10 trials). Tests for heterogeneity between subgroups were highly significant for PFS (P &lt; .001) and OS (P = .02). The median monthly prices for standard doses of drugs were $5,375 for group A, $5,644 for group B, and $6,584 for group C (P = .87). Conclusion New agents with specific molecular targets are clinically the most beneficial, but their monthly market prices are not significantly different from those of other anticancer agents.
Vascular cell adhesion molecule-1 and the integrin VLA-4 mediate adhesion of human B cell precursors to cultured bone marrow adherent cells.
Authors: D H Ryan, B L Nuccie, C N Abboud, J M Winslow
Journal: Journal of Clinical Investigation (1991)

Adhesion of B cell precursors to accessory cells in the bone marrow microenvironment may be required for normal early B cell development. Human bone marrow B cell precursors adhere more avidly than mature B cells to bone marrow-derived fibroblasts. To determine the mechanism of this adhesion, expression of adhesion proteins on human B precursor cells and cell lines was measured by flow cytometry. The very late antigen (VLA) integrins VLA-4 and VLA-5 were the only adhesion proteins expressed at higher levels in B cell precursors than mature B cells. Antibodies to the alpha and beta chains of VLA-4, but not VLA-5, significantly blocked binding to bone marrow-derived fibroblasts of immature B cells and cell lines. Although fibronectin is a ligand for VLA-4, anti-fibronectin antibody and a soluble fibronectin fragment containing the VLA-4 binding domain did not block adhesion, suggesting that VLA-4 is involved in adhesion of B cell precursors, but not as a fibronectin receptor. Vascular cell adhesion molecule-1 (VCAM-1), the other known counterreceptor for VLA-4, was identified on bone marrow-derived fibroblasts, and anti-VCAM-1 significantly blocked adhesion of normal B cell precursors to bone marrow-derived fibroblasts, indicating that VLA-4/VCAM-1 interactions are important in adhesion of B cell precursors to the bone marrow microenvironment.
Human and rabbit lung injuries caused by extreme cold presented by MDCT with perfusion and MRI with diffusion and DWI
Authors: Aleksandar Ivkovic, Tamara Milosavljevic, Zoran Radovanovic
Journal: European Respiratory Journal (2013)

Purpose: purpose is to show effects of extreme cold on lung tissue and to determine role of radiology in diagnostic and proper medical care.  Material: We examined 37 patients exposed to extreme cold. There were 24 female and 13 male patients. They were from 18 to 35 years old. All patients were examined on MDCT with perfusion and on 1.5T MRI with DWI. We perform MDCT pulmonary angiography on 16 patients. Also we had a group of 24 rabbits accidentally exposed to extreme cold.  Results: MDCT examination was performed in first 24 hour after arriving to hospital care. Additional MDCT angiography was performed in first 72 hours after arriving. MRI was performed 7 days after arriving. We separate results in 3 different subgroups according to patient’s conditions. First subgroup was patients with bronchiolitis of lower parts of lung with no other signs. Second subgroup was patients with bronchiolitis of all parts of lung. Third subgroup was patients with hard symptoms, all in intensive care unit. Radiology findings were from edema and reactive pneumonia to hematopneumotorax. On MDCT angiography we find thromboembolism of lower lung vessels. MDCT perfusion and MRI DWI were performed to determine borders and levels of injuries. Hyperpnoea of temperate air shares similar effects to the inhalation of cold air. Hyperpnoea of cold air may cause the ASL to evaporate more rapidly than it can be replaced. We compare results with rabbit exposed to extreme cold.  Conclusion: Extreme cold can make serious injuries to lung tissue. MDCT examination has a great role in diagnostic and follows up. MDCT perfusion and MRI DWI give us information about exact border of injuries and prognosis.
Observational study of the effect of obesity on lung volumes
Authors: Joerg Steier, Alan Lunt, Nicholas Hart, Michael I Polkey, John Moxham
Journal: Thorax (2014)

<h3>Background</h3> Severe obesity causes respiratory morbidity and mortality. The impact of obesity on the mechanics of breathing is not fully understood. <h3>Patients and methods</h3> We undertook a comprehensive observational study of lung volumes and elasticity in nine obese and nine normal weight subjects, seated and supine, during spontaneous breathing. Seated and supine total lung capacity (TLC) and subdivisions were measured by multibreath helium dilution method. Using balloon catheters, oesophageal (Poes) and gastric (Pgas) pressures were recorded. Transpulmonary pressure (P<sub>L</sub>) was calculated as mouth pressure (Pmouth)-Poes, and complete expiratory P<sub>L</sub> volume curves were measured. <h3>Results</h3> The obese group had a body mass index (BMI) of 46.8 (17.2) kg/m<sup>2</sup>, and the normal group had a BMI of 23.2 (1.6) kg/m<sup>2</sup> (p=0.001). Obese and normals were matched for age (p=0.233), gender (p=0.637) and height (p=0.094). The obese were more restricted than the normals (TLC 88.6 (16.9) vs 104.4 (12.3) %predicted, p=0.033; FEV<sub>1</sub>/FVC 79.6 (7.3) vs 82.5 (4.2) %, p=0.325), had dramatically reduced expiratory reserve volume (ERV 0.4 (0.4) vs 1.7 (0.6) L, p&lt;0.001) and end-tidal functional residual capacity (FRC) was smaller (37.5 (6.9) vs 46.9 (4.6) %TLC, p=0.004) when seated, but was similar when supine (39.4 (7.7) vs 41.5 (4.3) %TLC, p=0.477). Gastric pressures at FRC were significantly elevated in the obese (seated 19.1 (4.7) vs 12.1 (6.2) cm H<sub>2</sub>O, p=0.015; supine 14.3 (5.7) vs 7.1 (2.6) cm H<sub>2</sub>O, p=0.003), as were end-expiratory oesophageal pressures at FRC (seated 5.2 (6.9) vs −2.0 (3.5) cm H<sub>2</sub>O, p=0.013; supine 14.0 (8.0) vs 5.4 (3.1) cm H<sub>2</sub>O, p=0.008). BMI correlated with end-expiratory gastric (seated R<sup>2</sup>=0.43, supine R<sup>2</sup>=0.66, p&lt;0.01) and oesophageal pressures (seated R<sup>2</sup>=0.51, supine R<sup>2</sup>=0.62, p&lt;0.01). <h3>Conclusions</h3> Obese subjects have markedly increased gastric and oesophageal pressures, both when upright and supine, causing dramatically reduced FRC and ERV, which increases work of breathing.
HIV Vaccine Development: A Progress Report
Authors: Daniel F. Hoth
Journal: Annals of Internal Medicine (1994)

The development of a safe, effective preventive vaccine for human immunodeficiency virus (HIV) infection remains an area of vigorous research.Several highly innovative vaccine candidates are being developed, and more than 13 vaccine candidates have been tested in human phase I or II trials. All have produced antibody and several have produced modest neutralizing titers, but to date no reproducible evidence has suggested prolonged, high-titer neutralization across a diversity of HIV strains. Furthermore, only the live recombinant vector approaches have produced some evidence of cytotoxic T-cell responses. The principal obstacle to progress is the lack of definitive information on what constitutes a protective immune response. There is no animal model for HIV-induced disease. Hence, the identification of the correlates of immunity and more useful animal models is among the highest priorities for HIV vaccine research. Large-scale efficacy trials raise daunting scientific, ethical, and resource issues. Nonetheless, preparation in such trials is underway in order to be in a position to evaluate the most promising vaccine candidate.
The Potential Benefits of BIM in the Further Pursuit of Biomarker Discovery in Cancer Therapeutics
Authors: Takeshi Yoshida, Eric B. Haura
Journal: Cancer Discovery (2011)

Abstract In this issue of Cancer Discovery, Faber and colleagues demonstrate that the basal expression of BIM is positively correlated with the amount of apoptosis induced by the corresponding tyrosine kinase inhibitor treatment within the same subtype of several oncogene-addicted cancer cell types. Their results suggest that pre-treatment assessment of BIM levels can identify patients who would benefit from molecularly targeted therapies even after biomarker-based patient selection. Cancer Discovery; 1(4); 289–90. ©2011 AACR. Commentary on Faber et al., p. 352.
A gender-sensitised weight loss and healthy living programme for overweight and obese men delivered by Scottish Premier League football clubs (FFIT): a pragmatic randomised controlled trial
Authors: Kate Hunt, Sally Wyke, Cindy M Gray, Annie S Anderson, Adrian Brady, Christopher Bunn, Peter T Donnan, Elisabeth Fenwick, Eleanor Grieve, Jim Leishman, Euan Miller, Nanette Mutrie, Petra Rauchhaus, Alan White, Shaun Treweek
Journal: The Lancet (2014)

Background The prevalence of male obesity is increasing but few men take part in weight loss programmes.We assessed the eff ect of a weight loss and healthy living programme on weight loss in football (soccer) fans. MethodsWe did a two-group, pragmatic, randomised controlled trial of 747 male football fans aged 35-65 years with a body-mass index (BMI) of 28 kg/m² or higher from 13 Scottish professional football clubs.Participants were randomly assigned with SAS (version 9•2, block size 2-9) in a 1:1 ratio, stratifi ed by club, to a weight loss programme delivered by community coaching staff in 12 sessions held every week.The intervention group started a weight loss programme within 3 weeks, and the comparison group were put on a 12 month waiting list.All participants received a weight management booklet.Primary outcome was mean diff erence in weight loss between groups at 12 months, expressed as absolute weight and a percentage of their baseline weight.Primary outcome assessment was masked.Analyses were based on intention to treat.The trial is registered with Current Controlled Trials, number ISRCTN32677491.Findings 374 men were allocated to the intervention group and 374 to the comparison group.333 (89%) of the intervention group and 355 (95%) of the comparison group completed 12 month assessments.At 12 months the mean diff erence in weight loss between groups, adjusted for baseline weight and club, was 4•94 kg (95% CI 3•95-5•94) and percentage weight loss, similarly adjusted, was 4•36% (3•64-5•08), both in favour of the intervention (p<0•0001).Eight serious adverse events were reported, fi ve in the intervention group (lost consciousness due to drugs for pre-existing angina, gallbladder removal, hospital admission with suspected heart attack, ruptured gut, and ruptured Achilles tendon) and three in the comparison group (transient ischaemic attack, and two deaths).Of these, two adverse events were reported as related to participation in the programme (gallbladder removal and ruptured Achilles tendon).Interpretation The FFIT programme can help a large proportion of men to lose a clinically important amount of weight; it off ers one eff ective strategy to challenge male obesity.
Induction of Hyaluronic Acid Synthase 2 (HAS2) in Human Vascular Smooth Muscle Cells by Vasodilatory Prostaglandins
Authors: M. Sussmann, M. Sarbia, J. Meyer-Kirchrath, R.M. Nüsing, K. Schrör, J.W. Fischer
Journal: Circulation Research (2004)

Hyaluronic acid (HA) is a prominent constituent of the extracellular matrix of atherosclerotic vascular lesions in humans known to modulate vascular smooth muscle phenotype. The regulation of HA synthesis by vasodilatory prostaglandins was analyzed in human arterial smooth muscle cells (SMCs). The prostacyclin analogue, iloprost (100 nmol/L), markedly increased pericellular formation of HA coats and HA secretion into the cell culture medium in human arterial SMCs (8.7±1.6-fold). Expression of HA synthase 2 (HAS2) was determined by semiquantitative RT-PCR and found to be strongly upregulated at concentrations of iloprost between 1 and 100 nmol/L after 3 hours. Furthermore, endogenous cyclooxygenase-2 (COX2) activity was required for basal expression of HAS2 mRNA in SMCs in vitro. Total HA secretion in response to iloprost was markedly decreased by RNA interference (RNAi), specific for HAS2. In addition, siRNA targeting HAS2 strongly increased the spreading of human SMCs compared with mock-transfected cells. HAS2 mRNA levels were also stimulated by a selective prostacyclin receptor (IP) agonist, cicaprost (10 nmol/L), prostaglandin E 2 (10 nmol/L), and the EP 2 receptor agonist, butaprost (1 μmol/L). Induction of HAS2 mRNA and HA synthesis by prostaglandins was mimicked by stable cAMP analogues and forskolin. In human atherectomy specimens from the internal carotid artery, HA deposits and COX2 expression colocalized frequently. In addition, strong EP 2 receptor expression was detected in SMCs in HA-rich areas. Therefore, upregulation of HAS2 expression via EP 2 and IP receptors might contribute to the accumulation of HA during human atherosclerosis, thereby mediating proatherosclerotic functions of COX2.
Pregnancy After Breast Cancer Appears Safe
Authors: G. Sinha
Journal: JNCI Journal of the National Cancer Institute (2012)

hysicians have often assumed that pregnancy after breast cancer increases the risk of cancer recurrence.But research presented at the eighth European Breast Cancer Conference in March adds to the growing evidence that this assumption is wrong.In a retrospective analysis, Hatem Azim, M.D., a medical oncologist at the Jules Bordet Institute in Brussels, Belgium, reported that 333 women who became pregnant at any time after being diagnosed with breast cancer had no higher risk of recurrence than that of a control group of 874 breast cancer patients who did not become pregnant.All women in the study group were monitored for an average of 4.7 years after becoming pregnant.The study was the fi rst to look at estrogen receptor (ER) status in particular.Women with ER-positive (ER + ) breast cancers who became pregnant had no higher risk of cancer recurrence than that of women with ER-negative (ER Ϫ ) cancers.That pregnancy did not increase the risk of women with ER + breast cancer relapsing is especially signifi cant, said David Cameron, M.D., professor of oncology at the University of Edinburgh, Scotland."If pregnancy were to increase the chance that breast cancer would recur because of high levels of estrogen, one would expect to see increased risk only in women with ER + breast cancer, and one does not in this study.It ' s a very important study."Azim ' s study also implicitly suggests that aborting a pregnancy does not affect breast cancer recurrence.Some studies
BMP4 Administration Induces Differentiation of CD133+ Hepatic Cancer Stem Cells, Blocking Their Contributions to Hepatocellular Carcinoma
Authors: Lixing Zhang, Hefen Sun, Fangyu Zhao, Ping Lu, Chao Ge, Hong Li, Helei Hou, Mingxia Yan, Taoyang Chen, Guoping Jiang, Haiyang Xie, Ying Cui, Xiaowu Huang, Jia Fan, Ming Yao, Jinjun Li
Journal: Cancer Research (2012)

CD133+ cancer stem cells (CSC) contribute to hepatocellular carcinoma (HCC) progression and resistance to therapy. Bone morphogenetic protein BMP4 plays an important role in hepatogenesis and hepatic stem cell differentiation, but little is known about its function in hepatic CSCs. In this study, we showed that high-dose exogenous BMP4 promotes CD133+ HCC CSC differentiation and inhibits the self-renewal, chemotherapeutic resistance, and tumorigenic capacity of these cells. Interestingly, we found that low-dose exogenous BMP4 upregulated CD133 protein expression in vitro, and endogenous BMP4 was preferentially expressed in CD133+ HCC CSCs, suggesting that low doses of BMP4 may facilitate CSC maintenance. A reduction in endogenous BMP4 levels decreased CD133 protein expression in vitro. In HCC tissues, expression of the BMP4 signaling target gene SMAD6 was positively correlated with CD133 expression. Activation of the Erk1/2 signaling pathway led to BMP4-mediated reduction in CD133 expression, which was reversed by treatment with MEK inhibitors. Taken together, our findings indicated that BMP4 might be a potent therapeutic agent in HCC that targets CSCs.
Hydrogen peroxide induced adenosine diphosphate ribosyl transferase (ADPRT) response in patients with inflammatory bowel disease.
Authors: M M Markowitz, P Rozen, R W Pero, M Tobi, D G Miller
Journal: Gut (1988)

The sample population in this initial case control study of the adenosine diphosphate ribosyl transferase (ADPRT) response of inflammatory bowel disease patients included: 23 patients with ulcerative colitis (UC)-active and inactive, 13 patients with Crohn9s disease (CD)-active and inactive, 14 first degree relatives of UC and CD patients, and 19 age-matched controls. Adenosine diphosphate ribosyl transferase activity was determined after one hour incubation with 1% plasma (the constitutive value) or with 1% plasma and 100 microM H2O2 (the activated value) with the resulting difference designated as the induced value. Statistically significant decrease in ADPRT activity was found for the constitutive, activated and induced values in human mononuclear leucocytes of UC and CD patients, compared with controls. The values in the first degree relatives of UC and CD patients were not significantly different from either the control or disease populations, indicating an intermediate ADPRT response. These results may be related to the nature of the immunological response of IBD patients and comparable with similar findings in other diseases with known DNA repair deficiencies--for example, colon cancer.