tbuckley/cabot-search huggingface dataset:
Association of Nitrotyrosine Levels With Cardiovascular Disease and Modulation by Statin Therapy
Authors: Mehdi H. Shishehbor, Ronnier J. Aviles, Marie-Luise Brennan, Xiaoming Fu, Marlene Goormastic, Gregory L. Pearce, Noyan Gokce, John F. Keaney, Marc S. Penn, Dennis L. Sprecher, Joseph A. Vita, Stanley L. Hazen
Journal: JAMA (2003)

Formation of nitric oxide-derived oxidants may serve as a mechanism linking inflammation to development of atherosclerosis. Nitrotyrosine, a specific marker for protein modification by nitric oxide-derived oxidants, is enriched in human atherosclerotic lesions and low-density lipoprotein (LDL) recovered from human atheroma.To determine whether systemic levels of nitrotyrosine are associated with the prevalence of coronary artery disease (CAD) and are modulated by hydroxymethylglutaryl coenzyme-A reductase inhibitor (statin) therapy.A case-control and interventional study at 2 urban tertiary-care referral centers; recruitment for each was from June 1, 2001, until January 1, 2002. For the case-control study, 100 case-patients with established CAD and 108 patients with no clinically evident CAD were recruited consecutively. In the interventional study, participants aged 21 years or older with hypercholesterolemia (LDL cholesterol > or =130 mg/dL [> or =3.5 mmol/L]) underwent nutrition and exercise counseling. Those whose levels did not decrease with 6 to 8 weeks were enrolled in the study (n = 35). For 12 weeks, they received 10 mg/d of oral atorvastatin therapy.In the case-control study, the association between systemic levels of protein-bound nitrotyrosine, CAD risk, and presence of CAD. In the interventional study, the change in nitrotyrosine, lipoprotein, and C-reactive protein (CRP) levels.Nitrotyrosine levels were significantly higher among patients with CAD (median 9.1 micromol/mol [interquartile range, 4.8-13.8 micromol/mol] tyrosine vs 5.2 micromol/mol [interquartile range, 2.2-8.4 micromol/mol]; P<.001). Patients in the upper quartile of nitrotyrosine (29%; P<.001) had a higher odds of CAD compared with those in the lowest quartile (unadjusted odds ratio, 6.1; 95% confidence interval, 2.6-14.0; P<.001). In multivariate models adjusting for Framingham Global Risk Score and CRP, upper quartiles of nitrotyrosine remained associated with CAD (odds ratio, 4.4; 95% confidence interval, 1.8-10.6; P<.001). Statin therapy reduced nitrotyrosine levels significantly (25%; P<.02) with a magnitude similar to reductions in total cholesterol levels (25%; P<.001) and LDL particle number (29%; P<.001) yet were independent of alterations in lipoproteins and inflammatory markers like CRP.The findings from this preliminary study indicate that nitrotyrosine levels are associated with the presence of CAD and appear to be modulated by statin therapy. These results suggest a potential role for nitric oxide-derived oxidants as inflammatory mediators in CAD and may have implications for atherosclerosis risk assessment and monitoring of anti-inflammatory actions of statins.
Intestinal lymphangiectasia associated with angiofollicular lymph node hyperplasia (Castleman's disease).
Authors: S F Moss, D M Thomas, C Mulnier, I G McGill, H J Hodgson
Journal: Gut (1992)

A patient presenting with predominantly gastrointestinal symptoms and a history of myocardial infarction was found to have ascites, hepatosplenomegaly, para-aortic lymphadenopathy, thrombocytosis, and a paraproteinaemia. A jejunal biopsy specimen showed lymphangiectasia and histology of the spleen and lymph nodes showed angiofollicular hyperplasia or Castleman9s disease of the hyaline vascular type. This association has not previously been described and, moreover, systemic symptoms are unusual in this variant of Castleman9s disease.
SNPs and Haplotypes in <i>DPYD</i> and Outcome of Capecitabine–Response
Authors: Maarten J. Deenen, Jan H.M. Schellens, Annemieke Cats
Journal: Clinical Cancer Research (2011)

Opdam and colleagues and van Kuilenburg and colleagues address relevant issues concerning our article in which we assessed the effect of single-nucleotide polymorphisms and haplotypes within DPYD on toxicity and efficacy of capecitabine in patients with advanced colorectal cancer ([1][1]).

Opdam
Inhibition of Metastatic Tumor Growth in Mouse Lung by Repeated Administration of Polyethylene Glycol-Conjugated Catalase
Authors: Kenji Hyoudou, Makiya Nishikawa, Yukari Umeyama, Yuki Kobayashi, Fumiyoshi Yamashita, Mitsuru Hashida
Journal: Clinical Cancer Research (2004)

Abstract Purpose: To develop a novel and effective approach to inhibit tumor metastasis based on controlled delivery of catalase, we first evaluated the characteristics of the disposition and proliferation of tumor cells. Then, we examined the effects of polyethylene glycol-conjugated catalase (PEG-catalase) on tumor metastasis. On the basis of the results obtained, PEG-catalase was repetitively administered to completely suppress the growth of tumor cells. Experimental Design: Murine melanoma B16-BL6 cells were stably transfected with firefly luciferase gene to obtain B16-BL6/Luc cells. These cells were injected intravenously into syngeneic C57BL/6 mice. PEG-catalase was injected intravenously, and the effect was evaluated by measuring the luciferase activity as the indicator of the number of tumor cells. Results: At 1 hour after injection of B16-BL6/Luc cells, 60 to 90% of the injected cells were recovered in the lung. The numbers decreased to 2 to 4% at 24 hours, then increased. An injection of PEG-catalase just before inoculation significantly reduced the number of tumor cells at 24 hours. Injection of PEG-catalase at 1 or 3 days after inoculation was also effective in reducing the cell numbers. Daily dosing of PEG-catalase greatly inhibited the proliferation and the number assayed at 14 days after inoculation was not significantly different from the minimal number observed at 1 day, suggesting that the growth had been markedly suppressed by the treatment. Conclusions: These findings indicate that sustained catalase activity in the blood circulation can prevent the multiple processes of tumor metastasis in the lung, which could lead to a state of tumor dormancy.
A New Mechanism of NK Cell Cytotoxicity Activation: The CD40–CD40 Ligand Interaction
Authors: Ennio Carbone, Giuseppina Ruggiero, Giuseppe Terrazzano, Carmen Palomba, Ciro Manzo, Silvia Fontana, Hergen Spits, Klas Kärre, Serafino Zappacosta
Journal: The Journal of Experimental Medicine (1997)

NK recognition is regulated by a delicate balance between positive signals initiating their effector functions, and inhibitory signals preventing them from proceeding to cytolysis. Knowledge of the molecules responsible for positive signaling in NK cells is currently limited. We demonstrate that IL-2–activated human NK cells can express CD40 ligand (CD40L) and that recognition of CD40 on target cells can provide an activation pathway for such human NK cells. CD40-transfected P815 cells were killed by NK cell lines expressing CD40L, clones and PBLderived NK cells cultured for 18 h in the presence of IL-2, but not by CD40L-negative fresh NK cells. Cross-linking of CD40L on IL-2–activated NK cells induced redirected cytolysis of CD40-negative but Fc receptor-expressing P815 cells. The sensitivity of human TAP-deficient T2 cells could be blocked by anti-CD40 antibodies as well as by reconstitution of TAP/MHC class I expression, indicating that the CD40-dependent pathway for NK activation can be downregulated, at least in part, by MHC class I molecules on the target cells. NK cell recognition of CD40 may be important in immunoregulation as well as in immune responses against B cell malignancies.
Mandatory generic prescribing is expected to save Spain 2bn a year
Authors: A. Garcia Rada
Journal: BMJ (2011)

Spanish doctors will be required to prescribe generically wherever possible when a new law comes into force in the next few weeks—a move that health minister Leire Pajin has said will save the health service €2bn (£1.7bn; $2.9bn) a year. 

Another €400m will be cut from the country’s drugs bill by implementing other strategies. For example, 15% is being cut from the price of drugs that have been on the market more than 10 years and whose patent has expired but for which there is not yet a generic equivalent. Mechanisms for deciding on public funding for new drugs are also being strengthened. …
Chondrogenic and Adipogenic Potential of Microvascular Pericytes
Authors: C. Farrington-Rock, N.J. Crofts, M.J. Doherty, B.A. Ashton, C. Griffin-Jones, A.E. Canfield
Journal: Circulation (2004)

Background— Previous studies have shown that pericytes can differentiate into osteoblasts and form bone. This study investigated whether pericytes can also differentiate into chondrocytes and adipocytes. Methods and Results— Reverse transcription–polymerase chain reaction demonstrated that pericytes express mRNA for the chondrocyte markers Sox9, aggrecan, and type II collagen. Furthermore, when cultured at high density in the presence of a defined chondrogenic medium, pericytes formed well-defined pellets comprising cells embedded in an extracellular matrix rich in sulfated proteoglycans and type II collagen. In contrast, when endothelial cells were cultured under the same conditions, the pellets disintegrated after 48 hours. In the presence of adipogenic medium, pericytes but not endothelial cells expressed mRNA for peroxisome proliferator–activated receptor-γ2 (an adipocyte-specific transcription factor) and incorporated lipid droplets that stained with oil red O. To confirm that pericytes can differentiate along the chondrocytic and adipocytic lineages in vivo, these cells were inoculated into diffusion chambers and implanted into athymic mice for 56 days. Accordingly, mineralized cartilage, fibrocartilage, and a nonmineralized cartilaginous matrix with lacunae containing chondrocytes were observed within these chambers. Small clusters of cells that morphologically resembled adipocytes were also identified. Conclusions— These data demonstrate that pericytes are multipotent cells that may contribute to growth, wound healing, repair, and/or the development and progression of various pathological states.
Feeding Attitudes of Pregnant Women With Diabetes
Authors: Margreete Johnston, Cornelia Graves, Patrick G. Arbogast, William O. Cooper
Journal: Diabetes Care (2006)

The importance of breast milk in early childhood health and development is well known (1). While feeding decisions are known to be strongly influenced by socioeconomic, ethnical, and cultural characteristics (2,3), the impact of chronic illness on feeding attitudes has not been extensively studied. We proposed to compare feeding choices made by pregnant women with and without preexisting type 1 diabetes.

We surveyed pregnant women, with and without diabetes, regarding their feeding decisions in six diverse practices in Nashville, Tennessee, representing …
Characterization of desmin-positive rat liver sinusoidal cells
Authors: Mikihiro Tsutsumi, Akira Takada, Shujiro Takase
Journal: Hepatology (1987)

Hepatic sinusoidal lining cells were isolated from mature male rats (12 months old) and cultured in order to clarify the characteristics of the Ito cells (fat-storing cells). Desmin staining was used as a marker in the isolation of the Ito cells, and a highly purified desmin-positive cell fraction was obtained. Less than 10% of the desmin-positive cells were positive for vitamin A auto-fluorescence. However, the number of vitamin A-positive cells increased with vitamin A treatment, and they extended to over half of the desmin-positive cells by the first week of vitamin A treatment. The cultured Ito cells were positive for both desmin and vimentin stainings. On the other hand, Kupffer and endothelial cells were positive only with vimentin staining. Ito cells lost their fat droplets after repeated subculturing. The electron microscopic features of the Ito cells became similar to those of myofibroblasts, except for the absence of dense bodies, indicating that the Ito cells may have possibly transformed into myofibroblasts. Collagen fibers were occasionally found in the extracellular space. These results indicate that Ito cells retain both their myogenic and fibrogenic properties, and that lipocytes or myofibroblasts may be desmin-positive cells which maintain specific functions. Furthermore, staining of the intermediate filaments is useful in the identification of Ito cells, and a highly purified Ito cell fraction can be easily obtained using desmin staining as a marker.
Fluid Retention and Vascular Effects of Rosiglitazone in Obese, Insulin-Resistant, Nondiabetic Subjects
Authors: Alexander J.M. Rennings, Paul Smits, Murray W. Stewart, Cees J. Tack
Journal: Diabetes Care (2006)

OBJECTIVE—The use of thiazolidinedione (TZD) derivatives is associated with fluid retention, especially when combined with insulin. Because TZDs improve the metabolic effect of insulin, they may also reverse the blunted vascular response to insulin. We hypothesize that improvement of the action of insulin on vascular tone or permeability is the key mechanism of TZD-related fluid retention. RESEARCH DESIGN AND METHODS—In a randomized, double-blind, placebo-controlled, cross-over study in 18 obese, nondiabetic subjects with features of the metabolic syndrome, we investigated the effects of a 12-week treatment with 4 mg rosiglitazone twice a day on glucose disposal, hemodynamics (including forearm vasoconstrictor response to nitric oxide [NO]), synthase inhibition by N-monomethyl-l-arginine-acetate (l-NMMA), vascular permeability (transcapillary escape rate of albumin), and plasma volume during a hyperinsulinemic-euglycemic clamp (120 min, 120 mU/m2 per min). RESULTS—As expected, rosiglitazone increased the glucose infusion rate during clamping. However, neither vascular permeability nor forearm blood flow response to hyperinsulinemia or l-NMMA was affected by rosiglitazone. Compared with placebo, rosiglitazone decreased diastolic blood pressure by 5 mmHg (95% CI 2.35–6.87, P = 0.0005) and increased plasma volume by 255 ml/1.73 m2 (80–430, P = 0.007). Interestingly, the positive effect of rosiglitazone on glucose disposal correlated with change in foot volume (R2 = 0.53, P = 0.001). CONCLUSIONS—Rosiglitazone improved insulin sensitivity but had no effect on NO-dependent vasodilatation in the forearm or vascular permeability in obese, insulin-resistant, nondiabetic subjects. As such, TZD-related fluid retention was not caused by improvement of the vascular actions of insulin. Nonetheless, rosiglitazone-induced improvement in insulin sensitivity appears to be correlated to edema formation.
Stromal Cell–Immune Cell Interactions
Authors: Ramon Roozendaal, Reina E. Mebius
Journal: Annual Review of Immunology (2011)

Interaction between different types of hematopoietic cells is essential for proper functioning of the immune system. For instance, the cytokines produced by antigen-presenting dendritic cells will determine the type of T cell response that is induced. However, hematopoietic cells are also strongly influenced by the surrounding nonhematopoietic cells. The cells that form these microenvironments are collectively called stromal cells. Here, we focus on the stromal cells present within secondary lymphoid organs and discuss their importance for various aspects of the immune system.
Targeting of dobutamine to ischemic myocardium without systemic effects by selective suction and pressure-regulated retroinfusion
Authors: Georges von Degenfeld, Wolfgang Giehrl, Peter Boekstegers
Journal: Cardiovascular Research (1997)

Objective: To study the effects of low-dose dobutamine and/or glyceryl trinitrate in addition to selective suction and pressure-regulated retroinfusion with arterial blood on regional myocardial function of the ischemic myocardium and systemic hemodynamics. Methods: Using a pig model of repeated brief (90 s) occlusions of the left anterior descending artery, selective suction and pressure-regulated retroinfusion was carried out either with arterial blood alone (SSRalone) or with arterial blood and simultaneous application of low-dose dobutamine (0.1 μg/kg/min) (SSRDOB), glyceryl trinitrate (0.03 mg/kg/min) (SSRNIT) or the combination of both drugs (SSRDOB+NIT). Regional myocardial function of the ischemic and non-ischemic myocardium was determined by sonomicrometry (segment shortening). Results: Segment shortening in the ischemic area after 90 s of ischemia was preserved at 57.5±9.2% with SSRalone but at 78.0±22.3% of baseline with SSRDOB (P<0.05). The addition of glyceryl trinitrate did not improve regional myocardial function further. No effects of locally applied dobutamine were observed with regard to non-ischemic myocardium or heart rate. Cardiac output and mean arterial blood pressures tended to be further stabilized with SSRDOB. Conclusions: Local application of low-dose dobutamine together with arterial blood by selective suction and pressure-regulated retroinfusion during brief myocardial ischemia resulted in improved regional myocardial function without undesired effects on non-ischemic myocardium or systemic hemodynamics.
Macrophage deactivation by interleukin 10.
Authors: C Bogdan, Y Vodovotz, C Nathan
Journal: The Journal of Experimental Medicine (1991)

Recombinant mouse interleukin 10 (IL-10) was exceedingly potent at suppressing the ability of mouse peritoneal macrophages (m phi) to release tumor necrosis factor alpha (TNF-alpha). The IC50 of IL-10 for the suppression of TNF-alpha release induced by 0.5 microgram/ml lipopolysaccharide was 0.04 +/- 0.03 U/ml, with as little as 1 U/ml suppressing TNF-alpha production by a factor of 21.4 +/- 2.5. At 10 U/ml, IL-10 markedly suppressed m phi release of reactive oxygen intermediates (ROI) (IC50 3.7 +/- 1.8 U/ml), but only weakly inhibited m phi release of reactive nitrogen intermediates (RNI). Since TNF-alpha is a T cell growth and differentiation factor, whereas ROI and RNI are known to inhibit lymphocyte function, it is possible that m phi exposed to low concentrations of IL-10 suppress lymphocytes. m phi deactivated by higher concentrations of IL-10 might be permissive for the growth of microbial pathogens and tumor cells, as TNF-alpha, ROI, and RNI are major antimicrobial and tumoricidal products of m phi. IL-10's effects on m phi overlap with but are distinct from the effects of the two previously described cytokines that suppress the function of mouse m phi, transforming growth factor beta and macrophage deactivation factor. Based on results with neutralizing antibodies, all three m phi suppressor factors appear to act independently.
Quantitative Estimation of Insulin Sensitivity in Type 1 Diabetic Subjects Wearing a Sensor-Augmented Insulin Pump
Authors: Michele Schiavon, Chiara Dalla Man, Yogish C. Kudva, Ananda Basu, Claudio Cobelli
Journal: Diabetes Care (2013)

The goal was to develop a new index of insulin sensitivity in patients with type 1 diabetes estimated from continuous glucose monitoring (CGM) and subcutaneous insulin delivery data under carefully controlled conditions.The database consists of 12 subjects with type 1 diabetes, studied during breakfast, lunch, and dinner, in a clinical research unit, wearing both subcutaneous insulin pump and CGM device. Frequent blood samples were drawn for measurements of plasma glucose and insulin concentrations in order to estimate insulin sensitivity with the oral minimal model (SI(MM)). The new index of insulin sensitivity (SI(SP)) was calculated with a simple algebraic formula for each meal, using only CGM and insulin pump data and compared with SI(MM).SI(SP) was well correlated with SI(MM) (r = 0.825; P < 10(-8)), and diurnal pattern was also similar to SI(MM).A novel method for estimating insulin sensitivity in subjects with type 1 diabetes on sensor-augmented insulin pump therapy has been presented. This new index correlates well with the reference oral minimal model estimate of insulin sensitivity. The knowledge of patient-specific insulin sensitivity and its diurnal variation can help in optimizing insulin therapy in type 1 diabetes and could also inform next-generation closed-loop control systems.
Upregulation of aldolase B and overproduction of methylglyoxal in vascular tissues from rats with metabolic syndrome
Authors: Jianghai Liu, Rui Wang, Kaushik Desai, Lingyun Wu
Journal: Cardiovascular Research (2011)

Methylglyoxal (MG) overproduction has been reported in metabolic syndrome with hyperglycaemia (diabetes) or without hyperglycaemia (hypertension), and the underlying mechanism was investigated. Contributions of different pathways or enzymes to MG formation were evaluated in aorta or cultured vascular smooth muscle cells (VSMCs). In all four animal models of metabolic syndrome, i.e. chronically fructose-fed hypertensive Sprague–Dawley rats, spontaneously hypertensive rats, obese non-diabetic Zucker rats, and diabetic Zucker rats, serum and aortic MG and fructose levels were increased, and the expression of GLUT5 (transporting fructose) and aldolase B (converting fructose to MG) in aorta were up-regulated. Aortic expressions of aldolase A, semicarbazide-sensitive amine oxidase (SSAO), and cytochrome P450 2E1 (CYP 2E1), accounting for MG formation during glycolysis, protein, and lipid metabolism, respectively, was unchanged/reduced. Fructose (25 mM) treatment of VSMCs up-regulated the expression of GLUT5 and aldolase B and accelerated MG formation. Insulin (100 nM) increased GLUT5 expression and augmented fructose-increased cellular fructose accumulation and MG formation. Glucose (25 mM) treatment activated the polyol pathway and enhanced fructose formation, leading to aldolase B upregulation and MG overproduction. Inhibition of the polyol pathway reduced the glucose-increased aldolase B expression and MG generation. The excess formation of MG in under these conditions was eliminated by knock-down of aldolase B, but not by knock-down of aldolase A or inhibition of SSAO or CYP 2E1. Upregulation of aldolase B by accumulated fructose is a common mechanism for MG overproduction in VSMCs and aorta in different models of metabolic syndrome.
Antibody-targeted chemotherapy of older patients with acute myeloid leukemia in first relapse using Mylotarg (gemtuzumab ozogamicin)
Authors: RA Larson, M Boogaerts, E Estey, C Karanes, EA Stadtmauer, EL Sievers, P Mineur, JM Bennett, MS Berger, CB Eten, M Munteanu, MR Loken, JJM van Dongen, ID Bernstein, FR Appelbaum
Journal: Leukemia (2002)