tbuckley/cabot-search huggingface dataset:
Combined effects of exercise and restriction of energy intake on moderately obese women.
Authors: D P Thomas, A Z Belko, G L Mulroy, J D Haas, D A Roe
Journal: British Journal of Sports Medicine (1986)

The current study was designed to assess the contribution of dietary-induced weight reduction on improvements in functional capacity in moderate obesity. Twelve females (means age = 29 yr, means fat percentage = 37%) served as subjects for the study. Subjects trained on a cycle ergometer 30 min.day-1, six day.wk-1 for three or six weeks at 75 to 85 per cent of maximum heart rate (HR max). Improvements in maximal oxygen uptake (delta VO2 max I.min-1) and functional capacity (delta VO2 max ml.kg-1 min-1) were compared in an attempt to separate out training and dietary effects respectively. Measurements were also taken on both the cycle ergometer and treadmill to test for any specificity of training effects. Changes in body composition were assessed by densitometry. Following three weeks of training, there was an average increase in VO2 max ml.kg-1 min-1 on the cycle ergometer and the treadmill of 14 and 19 per cent respectively. By six weeks, this had increased to 18 and 26 per cent respectively. The contribution of weight reduction to the improvements in functional capacity was calculated to range from 20 to 33 per cent. Thus, both energy restriction and exercise training appear to be effective means of improving functional capacity in moderately obese women.
Fluticasone and salmeterol downregulate<i>in vitro</i>, fibroblast proliferation and ICAM-1 or H-CAM expression
Authors: M. Silvestri, L. Fregonese, F. Sabatini, G. Dasic, G.A. Rossi
Journal: European Respiratory Journal (2001)

β 2 -adrenoreceptor agonists have pharmacological properties that may suggest an inhibitory effect on various aspects of the inflammatory and repair processes that characterize asthma. Since fibroblasts express β 2 -adrenoreceptors, the effects of different concentrations (0.1–100 nM) of fluticasone propionate (FP), salmeterol (S) and their combination (FP+S) on lung fibroblast proliferation and adhesion molecule expression were evaluated. Stimulation of human foetal lung fibroblasts with a fibrogenic cytokine, basic fibroblast growth factor (bFGF), resulted in a [methyl- 3 H] thymidine ([ 3 H]TdR) uptake, four-fold higher than that of control cultures (p=0.0001) and was significantly inhibited by S, at all the concentrations tested (0.1–100 nM; p&lt;0.05). No changes in bFGF-induced cell proliferation were observed in the presence of FP (0.1–100 nM; p&gt;0.05, all comparisons). In addition, the association FP+S did not improve the inhibitory activity of S alone (p&gt;0.05, each comparison). An upregulation of intercellular adhesion molecule-1 (ICAM-1) expression was induced by tumour necrosis factor-α (TNF-α) (p=0.0004), but not by interleukin-4 (IL-4) (p&gt;0.05), while none of the two cytokines were able to increase hyaluronic-cellular adhesion molecule (H-CAM) expression by lung fibroblasts (p&gt;0.05). A significant downregulation of ICAM-1 or H-CAM expression was demonstrated in the presence of FP or S, at all concentrations tested (0.1–100 nM; p&lt;0.01, each comparison). Interestingly, S (10 nM and 100 nM) was able to enhance the inhibitory activity of FP on ICAM-1 expression (p&lt;0.01), but not on H-CAM expression (p&gt;0.1). These results show that in human foetal lung fibroblasts, fluticasone propionate and salmeterol are effective in modulating in vitro , different lung fibroblast biological functions that are likely to be involved in airway remodelling.
Influence of Coronary Artery Pressure Upon Myocardial Elasticity
Authors: PETER F. SALISBURY, CECIL E. CROSS, P. ANDRE RIEBEN
Journal: Circulation Research (1960)

The marked intensification of experimental left ventricular failure by veno-arterial pumping which was seen in earlier experiments suggested changes of myocardial elasticity as a mechanism. Two experimental procedures were therefore applied here, in which the pressure in the coronary arteries and veins could be varied at will, where the left ventricle was distended by an air-filled balloon, and where the coronary tree did not communicate with the left ventricle. Changes of the coronary arterial or venous pressures were accompanied by homodirectional changes of the left ventricular diastolic pressure which were of large magnitude and which could not be explained by unobserved blood flow into the left ventricle or by other factors. The inverse relationship between coronary vascular pressures and myocardial distensibility was probably caused by the increasing volume of blood which was retained in the coronary arteries and veins when the coronary arterial or venous pressures were increased. This passive increase in coronary blood volume (turgor) must have changed the resiliency of the coronary tree. The changed elastic properties of the coronary tree then resulted in a change of the elastic properties of the heart.
A Tertiary Plastid Gains RNA Editing in Its New Host
Authors: Christopher J. Jackson, Sebastian G. Gornik, Ross F. Waller
Journal: Molecular Biology and Evolution (2012)

Dinoflagellates are known for their development of highly aberrant organelle genetic systems. Both their plastid and mitochondrial genomes are extremely reduced in gene number and rearranged into numerous unconventional genomic elements. Transcription processes are also elaborately modified including extensive RNA editing and trans-splicing. Some dinoflagellates have replaced their original plastid through serial endosymbiotic events. Karlodinium veneficum is such an example that now contains a haptophyte plastid. This tertiary plastid provides a case of a more conventional genetic system introduced into a cellular environment with a known penchant for genetic oddities. Here, we show that K. veneficum plastid transcripts undergo extensive substitutional editing. The substitution types are more diverse than those seen in most other plastids but are similar to those of dinoflagellate organelles. There is no evidence for RNA editing of plastid-encoded transcripts from extant haptophytes, suggesting that K. veneficum plastid editing developed after the uptake of the tertiary endosymbiont.
The Presence of GAD and IA-2 Antibodies in Youth With a Type 2 Diabetes Phenotype
Authors: Georgeanna J. Klingensmith, Laura Pyle, Silva Arslanian, Kenneth C. Copeland, Leona Cuttler, Francine Kaufman, Lori Laffel, Santica Marcovina, Sherida E. Tollefsen, Ruth S. Weinstock, Barbara Linder
Journal: Diabetes Care (2010)

OBJECTIVE To determine the frequency of islet cell autoimmunity in youth clinically diagnosed with type 2 diabetes and describe associated clinical and laboratory findings. RESEARCH DESIGN AND METHODS Children (10–17 years) diagnosed with type 2 diabetes were screened for participation in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. Measurements included GAD-65 and insulinoma-associated protein 2 autoantibodies using the new National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health (NIDDK/NIH) standardized assays, a physical examination, and fasting lipid, C-peptide, and A1C determinations. RESULTS Of the 1,206 subjects screened and considered clinically to have type 2 diabetes, 118 (9.8%) were antibody positive; of these, 71 (5.9%) were positive for a single antibody, and 47 were positive (3.9%) for both antibodies. Diabetes autoantibody (DAA) positivity was significantly associated with race (P &amp;lt; 0.0001), with positive subjects more likely to be white (40.7 vs. 19%) (P &amp;lt; 0.0001) and male (51.7 vs. 35.7%) (P = 0.0007). BMI, BMI z score, C-peptide, A1C, triglycerides, HDL cholesterol, and blood pressure were significantly different by antibody status. The antibody-positive subjects were less likely to display characteristics clinically associated with type 2 diabetes and a metabolic syndrome phenotype, although the range for BMI z score, blood pressure, fasting C-peptide, and serum lipids overlapped between antibody-positive and antibody-negative subjects. CONCLUSIONS Obese youth with a clinical diagnosis of type 2 diabetes may have evidence of islet autoimmunity contributing to insulin deficiency. As a group, patients with DAA have clinical characteristics significantly different from those without DAA. However, without islet autoantibody analysis, these characteristics cannot reliably distinguish between obese young individuals with type 2 diabetes and those with autoimmune diabetes.
MicroRNA signatures characterize multiple myeloma patients
Authors: S L Corthals, S M Sun, R Kuiper, Y de Knegt, A Broyl, B van der Holt, H B Beverloo, J K Peeters, L el Jarari, H M Lokhorst, S Zweegman, M Jongen-Lavrencic, P Sonneveld
Journal: Leukemia (2011)
Indecisive interleukin-4?
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2005)

A study on page 1899 may explain the seemingly fickle ways of the cytokine interleukin (IL)-4. Yao and colleagues show how this quintessential T helper (Th) 2 cytokine can sometimes promote the opposite Th1 response.

IL-4 is known as the key cytokine for polarizing naive T cells toward a Th2 phenotype, which is important for antibody production and protection against parasitic infections. Under some conditions, however, IL-4 has been shown to instead induce a Th1 response. Indeed, a recent study showed that mice treated with IL-4 during initial infection with Leishmania major had increased Th1 responses and were protected. If given later, IL-4 increased Th2 responses and exacerbated disease.






Figure 

The prototypic Th2 cytokine IL-4 inhibits IL-10 production by DCs, thereby increasing the production of the Th1-promoting cytokine IL-12.




Yao et al. now suggest that the regulation of another cytokine—IL-10—may explain these perplexing observations. They show that dendritic cells (DCs) stimulated in the presence of IL-4 made less IL-10 than those stimulated without IL-4. As a result, the IL-4–treated DCs produced more of the Th1-polarizing cytokine IL-12—known to be inhibited by IL-10—and polarized naive T cells toward a Th1 phenotype more effectively. IL-10 was critical for the increased Th1 response, as IL-4 did not increase IL-12 production or T cell polarization by IL-10–deficient DCs.

IL-4 had the opposite effect on B cells, provoking increased IL-10 production. The authors suggest that the differential effect of IL-4 at different times during infection may reflect a switch from DCs to B cells as the predominant cell type that is presenting antigen.
Cheyne–Stokes respiration: friend or foe?: Figure 1
Authors: Matthew T Naughton
Journal: Thorax (2012)

<h3>Background</h3> Orthopnoea and paroxysmal nocturnal dyspnoea are common entities regularly confronting thoracic physicians, particularly those with an interest in sleep medicine or non-invasive ventilatory support. One major cause is heart failure (HF), usually associated with abnormal lung function tests, and either obstructive or central sleep apnoea with Cheyne–Stokes respiration (CSA–CSR). Whereas obstructive apnoea is considered injurious to the cardiovascular system, the effects of CSA–CSR are less clear and may be a compensatory response to severe HF. <h3>Aim</h3> To determine whether there are compensatory or possibly beneficial aspects caused by CSA–CSR in HF. <h3>Methods</h3> Literature review. <h3>Results</h3> CSA–CSR can be detrimental in terms of intermittent hypoxaemia, arousals and autonomic dysregulation. However, it is also associated with the beneficial effects of hyperventilation-related increases in end-expiratory lung volume, intrinsic positive airway pressure, assistance to stroke volume, attenuation of excessive sympathetic nervous activity, avoidance of hypercapnic acidosis and finally the provision of periodic rest to fatigue-prone respiratory pump muscles. <h3>Conclusions</h3> CSA–CSR has physiological features more likely to be compensatory and beneficial than injurious in HF. Some aspects of CSA–CSR are similar to those seen with positive airway pressure.
Low-grade mucosa-associated lymphoid tissue lymphoma: a retrospective analysis of 97 patients by the Hellenic Cooperative Oncology Group (HeCOG)
Authors: G. Papaxoinis, G. Fountzilas, D. Rontogianni, M.A. Dimopoulos, N. Pavlidis, C. Tsatalas, D. Pectasides, N. Xiros, T. Economopoulos
Journal: Annals of Oncology (2007)
Human Adult Vena Saphena Contains Perivascular Progenitor Cells Endowed With Clonogenic and Proangiogenic Potential
Authors: Paola Campagnolo, Daniela Cesselli, Ayman Al Haj Zen, Antonio Paolo Beltrami, Nicolle Kränkel, Rajesh Katare, Gianni Angelini, Costanza Emanueli, Paolo Madeddu
Journal: Circulation (2010)

Clinical trials in ischemic patients showed the safety and benefit of autologous bone marrow progenitor cell transplantation. Non-bone marrow progenitor cells with proangiogenic capacities have been described, yet they remain clinically unexploited owing to their scarcity, difficulty of access, and low ex vivo expansibility. We investigated the presence, antigenic profile, expansion capacity, and proangiogenic potential of progenitor cells from the saphenous vein of patients undergoing coronary artery bypass surgery.CD34-positive cells, negative for the endothelial marker von Willebrand factor, were localized around adventitial vasa vasorum. After dissection of the vein from surrounding tissues and enzymatic digestion, CD34-positive/CD31-negative cells were isolated by selective culture, immunomagnetic beads, or fluorescence-assisted cell sorting. In the presence of serum, CD34-positive/CD31-negative cells gave rise to a highly proliferative population that expressed pericyte/mesenchymal antigens together with the stem cell marker Sox2 and showed clonogenic and multilineage differentiation capacities. We called this population "saphenous vein-derived progenitor cells" (SVPs). In culture, SVPs integrated into networks formed by endothelial cells and supported angiogenesis through paracrine mechanisms. Reciprocally, endothelial cell-released factors facilitated SVP migration. These interactive responses were inhibited by Tie-2 or platelet-derived growth factor-BB blockade. Intramuscular injection of SVPs in ischemic limbs of immunodeficient mice improved neovascularization and blood flow recovery. At 14 days after transplantation, proliferating SVPs were still detectable in the recipient muscles, where they established N-cadherin-mediated physical contact with the capillary endothelium.SVPs generated from human vein CD34-positive/CD31-negative progenitor cells might represent a new therapeutic tool for angiogenic therapy in ischemic patients.
STUDIES ON THE RELATION BETWEEN TUMOR SUSCEPTIBILITY AND HEREDITY
Authors: Clara J. Lynch
Journal: The Journal of Experimental Medicine (1931)

A male mouse from a strain with a high incidence of spontaneous lung tumors was crossed with several females derived from a low tumor strain. The first generation of offspring were then backcrossed to individuals of the original strains. The resulting two groups of offspring differed significantly in the incidence of spontaneous tumors of the lung. These facts are discussed in relation to others previously discovered. It seems clear from the evidence presented that there are among mice constitutional types which differ in incidence of tumors of the lung and that the differences are inherited. The number of genetic factors involved has not been determined. No influence of sex was apparent. The possibility of there being genetic factors which affect tumor age will be dealt with later.
Loss of 1p, 19q, and 10q heterozygosity prospectively predicts prognosis of oligodendroglial tumors—towards individualized tumor treatment?
Authors: Carole Ramirez, Clive Bowman, Claude-Alain Maurage, François Dubois, Serge Blond, Nicole Porchet, Fabienne Escande
Journal: Neuro-Oncology (2010)

The purpose of this study was to determine whether chromosome 10q loss is a predictor of tumor aggressiveness and poor clinical outcome in patients with oligodendroglial tumors alone or together with loss of heterozygosity (LOH) on chromosomes 1p and 19q. A microsatellite analysis was performed on sections from 130 patients with grade II and grade III oligodendroglial tumors to assess the allelic status of chromosomes 1p, 19q, and 10q, plus detailed clinical and radiological information was taken prospectively. Median age at diagnosis was 45.5 years. Seventy-eight patients had disease progression after initial therapy; median progression-free survival (PFS) was 27.5 months. Age <47 years, postoperative Karnofsky performance score >65, no contrast enhancement on MRI, grade II, and complete removal on surgery were significantly correlated with a better PFS. Median overall survival (OS) was 40.5 months. Pure oligodendroglioma and temozolomide chemotherapy were correlated with better OS. 10q LOH was correlated with anaplastic grade and 1p19q LOH correlated with pure oligodendroglioma. There was a significant association between LOH status and the tumors' response to chemotherapy: 92.3% with 1p19q LOH, 83.3% without allelic losses, 50% with 1p19q10q LOH, and 14.5% with 10q LOH. Patients with 10q LOH alone had PFS of 6 months and a 3-year survival rate of 1%, when compared with 36 months and 85%, respectively, in patients with 1p19q LOH but without 10q LOH. 1p loss was correlated with better PFS (P < .005) and OS (P = .0007), whereas 10q loss was correlated with decreased PFS (P < .0001) and OS (P < .0001). 10q LOH predicted a survival disadvantage in patients with oligodendroglial tumors irrespective of 1p/19q LOH status.
A Phase I Trial of Immunotherapy with Lapuleucel-T (APC8024) in Patients with Refractory Metastatic Tumors that Express HER-2/neu
Authors: Prema P. Peethambaram, Michelle E. Melisko, Kristine J. Rinn, Steven R. Alberts, Nicole M. Provost, Lori A. Jones, Robert B. Sims, Lisa R. C. Lin, Mark W. Frohlich, John W. Park
Journal: Clinical Cancer Research (2009)

Abstract Purpose: This study aimed to evaluate the safety of, immune response induced by, and efficacy of treatment with lapuleucel-T (APC8024) in patients with HER-2/neu–expressing tumors. Lapuleucel-T is an investigational active immunotherapy product consisting of autologous peripheral blood mononuclear cells, including antigen presenting cells, which are cultured ex vivo with BA7072, a recombinant fusion antigen consisting of portions of the intracellular and extracellular regions of HER-2/neu linked to granulocyte-macrophage colony-stimulating factor. Experimental Design: Patients with metastatic breast, ovarian, or colorectal cancer whose tumors expressed HER-2 were eligible. Patients underwent leukapheresis in week 0 and received lapuleucel-T infusions in weeks 0, 2, and 4. Patients who achieved a partial response or had stable disease through week 48 were eligible for re-treatment using the same protocol and dose as their initial treatment. Results: Eighteen patients were enrolled and treated. Patients showed an immune response to the immunizing antigen (BA7072) at week 8 compared with week 0 as measured by T lymphocyte proliferation and IFN-γ enzyme-linked immunospot assay. Therapy was well tolerated. The majority (94.7%) of adverse events associated with treatment were grade 1 or 2. Two patients experienced stable disease lasting &amp;gt;48 weeks. Conclusions: Autologous active cellular immunotherapy with lapuleucel-T stimulated an immune response specific to the immunizing antigen and seemed to be well tolerated. Further clinical studies to assess the clinical benefit for patients with HER/2-neu–expressing breast, ovarian, and colorectal cancer are warranted. (Clin Cancer Res 2009;15(18):5937–44)
Possible role for a human adenovirus in the pathogenesis of celiac disease.
Authors: M F Kagnoff, R K Austin, J J Hubert, J E Bernardin, D D Kasarda
Journal: The Journal of Experimental Medicine (1984)

Celiac disease in humans is activated by the dietary ingestion of wheat, rye, triticale, barley, and possibly oats. Gliadins in wheat and similar proteins in the other grains are known to activate disease in susceptible individuals. There is a striking association between celiac disease and HLA-B8, -DR3 and/or -DR7, and -DC3. Nonetheless, less than 0.2% of individuals with those serologic HLA specificities develop celiac disease and disease is not always concordant among monozygotic twins. We propose that additional environmental factors may be important in the pathogenesis of celiac disease. To investigate that possibility, we examined a data bank of protein sequences for other proteins that might share amino acid sequence homologies with A-gliadin, an alpha-gliadin component known to activate celiac disease and whose complete primary amino acid sequence is known. These studies demonstrate that A-gliadin shares a region of amino acid sequence homology with the 54-kD E1b protein of human adenovirus type 12 (Ad12), an adenovirus usually isolated from the intestinal tract. The region spans 12 amino acid residues, includes 8 residue identities and an identical pentapeptide, and is hydrophilic in both proteins. Antibody reactive with the 54-kD Ad12 E1b protein cross-reacts with A-gliadin, a 119 amino acid cyanogen bromide peptide of A-gliadin that spans the region of homology and a synthetic heptapeptide of A-gliadin from within the region of homology. We suggest that an encounter of the immune system with antigenic determinants produced during intestinal viral infection may be important in the pathogenesis of celiac disease.
Stretch-Induced Alkalinization of Feline Papillary Muscle
Authors: H. E. Cingolani, B. V. Alvarez, I. L. Ennis, M. C. Camilión de Hurtado
Journal: Circulation Research (1998)

Myocardial stretch is a well-known stimulus that leads to hypertrophy. Little is known, however, about the intracellular pathways involved in the transmission of myocardial stretch to the cytoplasm and nucleus. Studies in neonatal cardiomyocytes demonstrated stretch-induced release of angiotensin II (Ang II). Because intracellular alkalinization is a signal to cell growth and Ang II stimulates the Na+/H+ exchanger (NHE), we studied the relationship between myocardial stretch and intracellular pH (pHi). Experiments were performed in cat papillary muscles fixed by the ventricular end to a force transducer. Muscles were paced at 0.2 Hz and superfused with HEPES-buffered solution. pHi was measured by epifluorescence with the acetoxymethyl ester form of the pH-sensitive dye 2',7'-bis(2-carboxyethyl)-5,6-carboxyfluorescein (BCECF-AM). Each muscle was progressively stretched to reach maximal developed force (Lmax) and maintained in a length that was approximately 92% Lmax (Li). During the "stretch protocol," muscles were quickly stretched to Lmax for 10 minutes and then released to Li; pHi significantly increased during stretch and came back to the previous value when the muscle was released to Li. The increase in pHi was eliminated by (1) specific inhibition of the NHE (EIPA, 5 micromol/L), (2) AT1-receptor blockade (losartan, 10 micromol/L), (3) inhibition of protein kinase C (PKC) (chelerythrine, 5 micromol/L), (4) blockade of endothelin (ET) receptors with a nonselective (PD 142,893, 50 nmol/L) or a selective ETA antagonist (BQ-123, 300 nmol/L). The increase in pHi by exogenous Ang II (500 nmol/L) was also reduced by both ET-receptor antagonists. Our results indicate that after myocardial stretch, pHi increases because of stimulation of NHE activity. This involves an autocrine-paracrine mechanism in which protein kinase C, Ang II, and ET play crucial roles.