tbuckley/cabot-search huggingface dataset:
Dietary Patterns and Incident Type 2 Diabetes in Chinese Men and Women
Authors: Andrew O. Odegaard, Woon-Puay Koh, Lesley M. Butler, Sue Duval, Myron D. Gross, Mimi C. Yu, Jian-Min Yuan, Mark A. Pereira
Journal: Diabetes Care (2011)

To empirically derive dietary patterns and examine their association with incident type 2 diabetes.We used data from the Singapore Chinese Health Study, including 43,176 Chinese men and women (aged 45-74 years), free of diabetes, cardiovascular disease, and cancer at baseline (1993-1998) and followed up through 2004. Two major dietary patterns were identified using principal components analysis: a vegetable, fruit, and soy-rich pattern (VFS) and a dim sum and meat-rich pattern (DSM). Pattern scores for each participant were calculated and examined with type 2 diabetes risk using Cox regression.The associations of the two dietary patterns with diabetes risk were modified by smoking status. Neither pattern was associated with risk of diabetes in ever smokers. In never smokers, the VFS dietary pattern was inversely associated with risk of type 2 diabetes. Compared with the lowest quintile of the VFS dietary pattern score, the hazard ratios (HRs) for quintiles 2-5 were 0.91, 0.82, 0.73, and 0.75 (P = 0.0005 for trend). The DSM dietary pattern was positively associated with risk of type 2 diabetes in never smokers, with HRs for quintiles 2-5 of 1.07, 1.25, 1.18, and 1.47 (P < 0.0001 for trend).A dietary pattern with higher intake of vegetables, fruits, and soy foods was inversely associated with risk of incident type 2 diabetes, and a pattern with higher intake of dim sum, meat and processed meat, sweetened foods and beverages, and fried foods was associated with a significantly increased risk of type 2 diabetes in Chinese men and women in Singapore.
Hypoglycemic Effect of <i>Opuntia streptacantha</i> Lemaire in NIDDM
Authors: Alberto C Frati-Munari, Blanca E Gordillo, Perla Altamirano, C Raúl Ariza
Journal: Diabetes Care (1988)

To assess the hypoglycemic effect of the nopal Opuntia streptacantha Lemaire (O. streptacantha Lem.), three groups of patients with non-insulin-dependent diabetes mellitus (NIDDM) were studied. Group one (16 patients) ingested 500 g of broiled nopal stems. Group 2 (10 patients) received only 400 ml of water as a control test. Three tests were performed on group 3 (6 patients): one with nopal, a second with water, and a third with ingestion of 500 g broiled squash. Serum glucose and insulin levels were measured at 0, 60, 120, and 180 min. After the intake of O. streptacantha Lem., serum glucose and serum insulin levels decreased significantly in groups 1 and 3, whereas no similar changes were noticed in group 2. The mean reduction of glucose reached 17.6 +/- 2.2% of basal values at 180 min in group 1 and 16.2 +/- 1.8% in group 3; the reduction of serum insulin at 180 min reached 50.2 +/- 8.0% in group 1 and 40.3 +/- 12.4% in group 3. This study shows that the stems of O. streptacantha Lem. cause a hypoglycemic effect in patients with NIDDM. The mechanism of this effect is unknown, but an increased insulin sensitivity is suggested.
Clinical and biological characteristics of cervical neoplasias with FGFR3 mutation.
Authors: Christophe Rosty, Marie-Hélène Aubriot, David Cappellen, Jérôme Bourdin, Isabelle Cartier, Jean Thiery, Xavier Sastre-Garau, François Radvanyi
Journal: Molecular Cancer (2005)

We have previously reported activating mutations of the gene coding for the fibroblast growth factor receptor 3 (FGFR3) in invasive cervical carcinoma. To further analyze the role of FGFR3 in cervical tumor progression, we extended our study to screen a total of 75 invasive tumors and 80 cervical intraepithelial neoplasias (40 low-grade and 40 high-grade lesions). Using single strand conformation polymorphism (SSCP) followed by DNA sequencing, we found FGFR3 mutation (S249C in all cases) in 5% of invasive cervical carcinomas and no mutation in intraepithelial lesions. These results suggest that, unlike in bladder carcinoma, FGFR3 mutation does not or rarely occur in non invasive lesions. Compared to patients with wildtype FGFR3 tumor, patients with S249C FGFR3 mutated tumors were older (mean age 64 vs. 49.4 years, P = 0.02), and were more likely to be associated with a non-16/18 HPV type in their tumor. Gene expression analysis demonstrated that FGFR3 mutated tumors were associated with higher FGFR3b mRNA expression levels compared to wildtype FGFR3 tumors. Supervised analysis of Affymetrix expression data identified a significant number of genes specifically differentially expressed in tumors with respect to FGFR3 mutation status. This study suggest that tumors with FGFR3 mutation appear to have distinctive clinical and biological characteristics that may help in defining a population of patients for FGFR3 mutation screening.
Spain plans to recoup 1bn by properly charging EU countries for their citizens' use of its health services
Authors: A. Garcia Rada
Journal: BMJ (2012)

The Spanish government plans to save €1bn by more efficiently billing health tourists’ countries of origin. At the moment Spain misses out on the money because of an incorrect interpretation of European Union regulations on healthcare provided to foreigners, concludes a recent report of the Court of Accounts.

The report says that the wrong interpretation of the EU directive 2004/38 on the free movement of citizens within the EU cost Spain €917m (£750m; $1.2bn) in 2009 for healthcare it provided to 700 000 foreigners, for which regional governments failed to extract reimbursement from the home countries. 

Ana Mato, Spain’s minister of health, social services, and equality, and the heads of regional health departments announced the measure among others to …
Autoantigen BiP‐Derived HLA–DR4 Epitopes Differentially Recognized by Effector and Regulatory T Cells in Rheumatoid Arthritis
Authors: Hirofumi Shoda, Keishi Fujio, Keiichi Sakurai, Kazuyoshi Ishigaki, Yasuo Nagafuchi, Mihoko Shibuya, Shuji Sumitomo, Tomohisa Okamura, Kazuhiko Yamamoto
Journal: Arthritis & Rheumatology (2015)

The balance between effector and regulatory CD4+ T cells plays a key role in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to examine whether the RA autoantigen BiP has epitopes for both effector and regulatory immunities. The proliferation and cytokine secretion of peripheral blood mononuclear cells (PBMCs) from HLA-DR4-positive RA patients in response to BiP-derived peptides were examined by (3)H-thymidine uptake and enzyme-linked immunosorbent assay. As a mouse therapeutic model, a BiP-derived peptide was administered orally to mice with collagen-induced arthritis (CIA). Among the peptides examined, BiP(336-355) induced the strongest proliferation of PBMCs from RA patients, but not from healthy donors. The proliferation of PBMCs in response to BiP(336-355) showed a correlation with clinical RA activity and serum anti-BiP/citrullinated BiP antibodies. In contrast, BiP(456-475) induced interleukin-10 (IL-10) secretion from CD25-positive PBMCs obtained from RA patients and healthy donors without inducing cell proliferation, and it actively suppressed the BiP(336-355)-induced proliferation and proinflammatory cytokine secretion by PBMCs. Oral administration of BiP(456-475) to mice with CIA reduced the severity of arthritis and T cell proliferation and increased the secretion of IL-10 from T cells as well as the number of CD4+CD25+FoxP3+ regulatory T cells. Effector and regulatory T cells recognized different BiP epitopes. The deviated balance toward BiP-specific effector T cells in RA may be associated with disease activity; therefore, BiP-specific effector or regulatory T cells could be a target of new RA therapies.
Platelet-Derived Growth Factor-AB Promotes the Generation of Adult Bone Marrow–Derived Cardiac Myocytes
Authors: Munira Xaymardan, Lilong Tang, Leze Zagreda, Benedetta Pallante, Jingang Zheng, Joseph L. Chazen, Andrew Chin, Inga Duignan, Patrick Nahirney, Shahin Rafii, Takashi Mikawa, Jay M. Edelberg
Journal: Circulation Research (2004)

The directed generation of cardiac myocytes from endogenous stem cells offers the potential for novel therapies for cardiovascular disease. To facilitate the development of such approaches, we sought to identify and exploit the pathways directing the generation of cardiac myocytes from adult rodent bone marrow cells (BMCs). In vitro cultures supporting the spontaneous generation of functional cardiac myocytes from murine BMCs demonstrated induced expression of platelet-derived growth factor (PDGF)-A and -B isoforms with α- and β-myosin heavy chains as well as connexin43. Supplementation of PDGF-AB speeded the kinetics of myocyte development in culture by 2-fold. In a rat heart, myocardial infarction pretreatment model PDGF-AB also promoted the derivation of cardiac myocytes from BMCs, resulting in a significantly greater number of islands of cardiac myocyte bundles within the myocardial infarction scar compared with other treatment groups. However, gap junctions were detected only between the cardiac myocytes receiving BMCs alone, but not BMCs injected with PDGF-AB. Echocardiography and exercise testing revealed that the functional improvement of hearts treated with the combination of BMCs and PDGF-AB was no greater than with injections of BMCs or PDGF-AB alone. These studies demonstrated that PDGF-AB enhances the generation of BMC-derived cardiac myocytes in rodent hearts, but suggest that alterations in cellular patterning may limit the functional benefit from the combined injection of PDGF-AB and BMCs. Strategies based on the synergistic interactions of PDGF-AB and endogenous stem cells will need to maintain cellular patterning in order to promote the restoration of cardiac function after acute coronary occlusion. The full text of this article is available online at http://circres.ahajournals.org.
Recovery of left ventricular function and sleep apnoea after acute myocardial infarction
Authors: Tanja Greimel, Stefan Buchner, Michael Arzt
Journal: European Respiratory Journal (2013)

Recovery of left ventricular function and sleep apnoea after acute myocardial infarctionFrom the authors:We are pleased to have the opportunity to compare our findings [1] with the similar observational study in patients with acute coronary syndrome by SCHIZA et al. [2].Since the two studies were published almost simultaneously in 2012 there has not yet been the opportunity to do so.
Primary mediastinal B-cell lymphoma treated with CHOP-like chemotherapy with or without rituximab: results of the Mabthera International Trial Group study
Authors: M. Rieger, A. Österborg, R. Pettengell, D. White, D. Gill, J. Walewski, E. Kuhnt, M. Loeffler, M. Pfreundschuh, A.D. Ho
Journal: Annals of Oncology (2010)
Stress and bacteria: microbial endocrinology
Authors: P. Everest
Journal: Gut (2007)

Regulation of virulence of Campylobacter jejuni by norepinephrine has implications for the husbandry of food production animals and transmission of infection to man

Bacteria living within the environs of a host (whether human or animal) are subject to stressful conditions and have to overcome them to survive.1,2 In particular, enteric bacterial pathogens have to tolerate exposure to the acid environment of the stomach, resist the detergent-like activity of bile salts and ever decreasing oxygen concentrations as they descend the gastrointestinal tract, the presence of a competing microbial flora and the antimicrobial peptides of the epithelial surfaces they encounter. Bacteria—whether commensal, obligate or opportunist pathogens—live in a permanent state of stress and regulate their gene expression and, in the case of potential pathogens, virulence gene expression1,2 in response to these environmental stresses.

The mammalian or avian hosts harbouring these organisms may themselves be subject to conditions that induce stress and the physiological responses that characterise that rather imprecise term. Thus, ill human patients in hospital—whether due to acute illness, infection, any form of accidental/induced trauma or animals reared and transported under some food production conditions—have a neurophysiological response to stress by the local (enteric) and systemic release of catecholamine hormones and, in particular, norepinephrine (noradrenaline) by the enteric nervous system.3,4

It has been recognised for some time that norepinephrine potentiates bacterial growth both in vivo and in vitro and induces expression of virulence determinants in enteric pathogens, particularly Escherichia coli .5,6 In this issue of Gut , Cogan et al 7 ( see page 1060 ) provide evidence that norepinephrine also regulates virulence in the important intestinal food-borne pathogen …
Effects of inhaled salbutamol in exercising non-asthmatic athletes
Authors: Goubault C, Perault Mc, Leleu E, Bouquet S, Legros P, Vandel B, Denjean A
Journal: Thorax (2001)

Background-Beta-2 agonists such as salbutamol are used, not only by asthmatic athletes to prevent exercise induced asthma, but also by non-asthmatic athletes as a potentially ergogenic agent.We have investigated whether inhaled salbutamol enhances endurance performance in non-asthmatic athletes.Methods-A prospective double blind, randomised, three way crossover design was used to study the eVects of 200 µg and 800 µg inhaled salbutamol versus a placebo in 12 trained triathletes.The treatments were compared in three identical cycle ergometer sessions at 85% of the predetermined maximal oxygen uptake.Lung function, endurance time, metabolic parameters (glucose, potassium, lactate, free fatty acid, and glycerol), and psychomotor performance were evaluated.Results-Neither endurance time nor post-exercise bronchodilation were significantly diVerent between the treatments.Metabolic parameters were aVected by exercise but not by treatment.Conclusions-Inhaled salbutamol, even in a high dose, did not have a significant eVect on endurance performance in nonasthmatic athletes, although the bronchodilating eVect of the drug at the beginning of exercise may have improved respiratory adaptation.Our results do not preclude an ergogenic eVect of 2 agonists given by other routes or for a longer period.
Clinical diversity of sickle cell anemia: Genetic and cellular modulation of disease severity
Authors: Martin H. Steinberg, Robert P. Hebbel
Journal: American Journal of Hematology (1983)

Abstract There is a great diversity in the clinical manifestations of sickle cell anemia. Some patients have severe repetitive infarctive episodes culminating in organ failure. Others have minor and nonincapacitating problems. This review focuses on the cellular and genetic factors that may play a role in modulating the clinical effects of the sickle hemoglobin gene. Understanding the role of putative modulators of disease severity may in the future allow the introduction of novel methods of therapy.
Endostatin Overexpression Inhibits Lymphangiogenesis and Lymph Node Metastasis in Mice
Authors: Gaëlle Brideau, Markus J. Mäkinen, Harri Elamaa, Hongmin Tu, Gunnar Nilsson, Kari Alitalo, Taina Pihlajaniemi, Ritva Heljasvaara
Journal: Cancer Research (2007)

Abstract Endostatin, a proteolytic fragment of collagen XVIII, is a potent inhibitor of angiogenesis and tumor growth. We studied the development of carcinogen-induced skin tumors in transgenic J4 mice overexpressing endostatin in their keratinocytes. Unexpectedly, we did not observe any differences in tumor incidence and multiplicity between these and control mice, nor in the rate of conversion of benign papillomas to malignant squamous cell carcinomas (SCC). We did find, however, that endostatin regulates the terminal differentiation of keratinocytes because the SCCs in the J4 mice were less aggressive and more often well differentiated than those in the control mice. We observed an inhibition of tumor angiogenesis by endostatin at an early stage in skin tumor development, but more strikingly, there was a significant reduction in lymphatic vessels in the papillomas and SCCs in association with elevated endostatin levels and also a significant inhibition of lymph node metastasis in the J4 mice. We showed that tumor-infiltrating mast cells strongly expressed vascular endothelial growth factor-C (VEGF-C), and that the accumulation of these cells was markedly decreased in the tumors of the J4 mice. Moreover, endostatin inhibited the adhesion and migration of murine MC/9 mast cells on fibronectin in vitro. Our data suggest that endostatin can inhibit tumor lymphangiogenesis by decreasing the VEGF-C levels in the tumors, apparently via inhibition of mast cell migration and adhesion, and support the view that the biological effects of endostatin are not restricted to endothelial cells because endostatin also regulates tumor-associated inflammation and differentiation, and the phenotype of epithelial tumors. [Cancer Res 2007;67(24):11528–35]
Increased eNOS expression as a compensatory mechanism reducing β-adrenergic responsiveness?
Authors: F MULLER
Journal: Cardiovascular Research (2005)

See article by Danson et al.  [13]  (pages 613–623) in this issue .

Nitric oxide (NO) is an important regulatory factor of the cardiovascular system mediating endothelium-dependent vasodilatation and modulating different facets of cardiac function including heart rate, contraction, relaxation, cell growth, and survival [1–3]. NO is synthesized from l-arginine by NO synthases (NOS), a family of isoenzymes with characteristic functional and regulatory properties [4]. All three NOS isoforms, i.e. the neural isoform (nNOS), the inducible isoform (iNOS, induced upon stimulation with appropriate inflammatory mediators), and the endothelial isoform (eNOS), can be expressed within various cell types in cardiac muscle. In the heart, eNOS was identified in endocardial and endothelial cells, in cardiomyocytes, and in specialized cells of the conducting system of the sinus and atrioventricular nodes [1–4]. Therefore, NO derived from different isoenzymes expressed in diverse cell types may modulate cardiac function in a paracrine/autocrine manner. As a consequence, differential local NO levels may contribute to the conflicting paradigms on cardiac function of eNOS which were deduced from studies on different experimental models, namely isolated cardiac myocytes, isolated cardiac muscle preparations or assessment of cardiac function in vivo, in eNOS-deficient or eNOS-overexpressing mice (see below) [1,3].

Under basal conditions (i.e. in the absence of agonist stimulation, e.g. by catecholamines), a concentration-dependent, biphasic inotropic effect of exogenous NO was reported by different studies, while endogenous NO may exert a positive inotropic effect (for a detailed review on eNOS function in the heart and …
Angiogenesis of Breast Cancer
Authors: Bryan P. Schneider, Kathy D. Miller
Journal: Journal of Clinical Oncology (2005)

Angiogenesis, the process of new blood vessel formation, plays a central role in both local tumor growth and distant metastasis in breast cancer. Extensive laboratory data suggest that angiogenesis plays an essential role in breast cancer development, invasion, and metastasis. Hyperplastic murine breast papillomas and histologically normal lobules adjacent to cancerous breast tissue support angiogenesis in preclinical models, suggesting that angiogenesis precedes transformation of mammary hyperplasia to malignancy. Transfection of tumor cells with angiogenic stimulatory peptides has been shown to increase tumor growth, invasiveness, and metastasis. Conversely, transfection of tumor cells with inhibitors of angiogenesis decreases growth and metastasis. The matrix metalloproteinase (MMP) family of enzymes degrades the basement membrane and extracellular matrix and is associated with a family of endogenous inhibitors, tissue inhibitors ofmetalloproteinases (TIMPs). Under normal physiologic conditions, the MMPs and TIMPs exist in anexquisitebalance.Thisbalance isdisrupted during active angiogenesis. Expression of MMPs increases with the progression from benign to preinvasive, invasive, and metastatic breast cancer and is associated with increasing histologic tumor grade. Microscopic metastases are growth restricted and remain dormant until they undergo an angiogenic switch, presumably a result of further mutation. This angiogenic switch often results in increased expression of MMPs. Hypoxia is a key signal for the induction of angiogenesis. Hypoxia-inducible factors (HIF-1 and HIF-2) are heterodimeric transcription factors consisting of and subunits. The subunit is constitutively expressed while the subunit is protected from degradation only under hypoxic condition. HIF-1 expression progressively increases from normal breast tissue to usual ductal hyperplasia to ductal carcinoma-insitu to invasive ductal carcinoma. HIF-1 expression is higher in poorly differentiated than in well-differentiated lesions and is associated with increased proliferation and expression of the estrogen receptor and vascular endothelial growth factor (VEGF). Similarly, expression of carbonic anhydrase IX, an HIF-1 -dependant enzyme important in pH regulation, is associated with worse relapse-free and overall survival in patients with invasive breast cancer.
Existing and Emerging Technologies for Tumor Genomic Profiling
Authors: Laura E. MacConaill
Journal: Journal of Clinical Oncology (2013)

Ongoing global genome characterization efforts are revolutionizing our knowledge of cancer genomics and tumor biology. In parallel, information gleaned from these studies on driver cancer gene alterations--mutations, copy number alterations, translocations, and/or chromosomal rearrangements--an be leveraged, in principle, to develop a cohesive framework for individualized cancer treatment. These possibilities have been enabled, to a large degree, by revolutionary advances in genomic technologies that facilitate systematic profiling for hallmark cancer genetic alterations at increasingly fine resolutions. Ongoing innovations in existing genomics technologies, as well as the many emerging technologies, will likely continue to advance translational cancer genomics and precision cancer medicine.