tbuckley/cabot-search huggingface dataset:
Trypsin and chymotrypsin in duodenal aspirate and faeces in response to secretin and cholecystokinin-pancreozymin
Authors: J. K. Sale, D. M. Goldberg, B. Thjodleifsson, K. G. Wormsley
Journal: Gut (1974)

The secretion of trypsin and chymotrypsin into the duodenum in response to secretin and CCK-PZ has been compared with the faecal excretion of the enzymes following similar stimulation in 47 individuals undergoing clinical investigation. The faecal output of chymotrypsin correlated well, but trypsin less satisfactorily, with the secretion of the respective enzymes into the duodenum. The faecal excretion of chymotrypsin following stimulation with secretin and CCK-PZ can therefore be used as an index of pancreatic enzyme-secretory capacity.
Type III Hyperlipoproteinemia: Diagnosis, Molecular Defects, Pathology, and Treatment
Authors: H. BRYAN BREWER
Journal: Annals of Internal Medicine (1983)

Type III hyperlipoproteinemia is characterized by increased plasma levels of triglycerides and cholesterol, palmar-tuberoeruptive xanthoma, and premature cardiovascular disease. Three major classes of molecular defects will predispose patients to develop type III hyperlipoproteinemia: a deficiency in apolipoprotein E, a structural defect in the E apolipoprotein, and a functional defect in the liver receptor system. Most patients with type III hyperlipoproteinemia have a structural defect in apolipoprotein E associated with increased synthesis and decreased catabolism of apolipoprotein E, delayed catabolism of chylomicron remnants, and development of plasma lipoprotein abnormalities characteristic of type III hyperlipoproteinemia. Analysis of cardiovascular disease in patients with type III hyperlipoproteinemia showed extensive coronary and peripheral vascular atherosclerosis indistinguishable from the atherosclerosis of non-hyperlipidemic and other dyslipoproteinemic patients. The xanthoma and elevated plasma cholesterol and triglyceride levels in patients with type III hyperlipoproteinemia respond to dietary and drug therapy.
Pathogenesis of cyclosporine nephropathy
Authors: R H Pichler, N Franceschini, B A Young, C Hugo, T F Andoh, E A Burdmann, S J Shankland, C E Alpers, W M Bennett, W G Couser
Journal: Journal of the American Society of Nephrology (1995)

Low-salt-diet, cyclosporine (CsA; 15 mg/kg per day)-treated rats develop striped interstitial fibrosis, arteriolar hyalinosis, and azotemia similar to the chronic nephropathy observed in humans. To examine the role of angiotensin II in this model, rats on a low-salt diet were given CsA, CsA and the angiotensin II receptor Type I antagonist Losartan (10 mg/kg per day), CsA and hydralazine/furosemide, or vehicle. At Day 35, CsA-treated rats had tubular injury, arteriolopathy of the afferent arteriole, increased expression of the monocyte-macrophage adhesive protein osteopontin, interstitial macrophage infiltration, increased interstitial transforming growth factor-beta expression, and interstitial fibrosis. This study provides new insight in both pathogenic and therapeutic aspects of CsA nephropathy. The pathogenesis of CsA nephropathy involves the expression of osteopontin by tubular epithelial cells, the level of which closely correlates with the degree of macrophage infiltration and interstitial fibrosis in all groups (r = 0.79 and 0.74, respectively; P < 0.001). Therapeutic conclusions can be drawn from the observation that both losartan and hydralazine/furosemide reduced osteopontin expression, macrophage infiltration, transforming growth factor-beta expression, and interstitial fibrosis, but did not prevent the decrease in GFR. Treatment with losartan, but not with hydralazine and furosemide, markedly reduced arteriolopathy. It was concluded that angiotensin II contributes to the vasculopathy (hyalinosis) induced by CsA. In contrast, the interstitial fibrosis mediated by CsA can be partially prevented by both an angiotensin II Type I receptor antagonist or by hydralazine and furosemide. This suggests that the interstitial fibrosis can be dissociated from the vascular effects of CsA. The beneficial effects of lowering blood pressure or vasodilation per se may be difficult to distinguish from the specific effects of angiotensin II receptor blockade.
Sailing and sports medicine: a literature review
Authors: J B Allen, M R De Jong
Journal: British Journal of Sports Medicine (2006)

Sailing medicine has been mainly addressed by healthcare professionals who happen to sail. Although there has been an increase in the number of studies of various aspects of sailing over the last 15 years, efforts to advance evidence based knowledge of sailing and sports medicine face unique obstacles. Recent interest in research by groups such as Olympic and America’s Cup teams has produced beneficial changes.
Multifunctional Nanoparticles for Combining Ultrasonic Tumor Imaging and Targeted Chemotherapy
Authors: Natalya Rapoport, Zhonggao Gao, Anne Kennedy
Journal: JNCI Journal of the National Cancer Institute (2007)

Drug delivery in polymeric micelles combined with tumor irradiation by ultrasound results in effective drug targeting, but this technique requires prior tumor imaging. A technology that combined ultrasound imaging with ultrasound-mediated nanoparticle-based targeted chemotherapy could therefore have important applications in cancer treatment.Mixtures of drug-loaded polymeric micelles and perfluoropentane (PFP) nano/microbubbles stabilized by the same biodegradable block copolymer were prepared. Size distribution of nanoparticles was measured by dynamic light scattering. Cavitation activity (oscillation, growth, and collapse of microbubbles) under ultrasound was assessed based on the changes in micelle/microbubble volume ratios. The effect of the nano/microbubbles on the ultrasound-mediated cellular uptake of doxorubicin (Dox) in MDA MB231 breast tumors in vitro and in vivo (in mice bearing xenograft tumors) was determined by flow cytometry. Statistical tests were two-sided.Phase state and nanoparticle sizes were sensitive to the copolymer/perfluorocarbon volume ratio. At physiologic temperatures, nanodroplets converted into nano/microbubbles. Doxorubicin was localized in the microbubble walls formed by the block copolymer. Upon intravenous injection into mice, Dox-loaded micelles and nanobubbles extravasated selectively into the tumor interstitium, where the nanobubbles coalesced to produce microbubbles with a strong, durable ultrasound contrast. Doxorubicin was strongly retained in the microbubbles but released in response to therapeutic ultrasound. Microbubbles cavitated under the action of tumor-directed ultrasound, which enhanced intracellular Dox uptake by tumor cells in vitro to a statistically significant extent relative to that observed with unsonicated microbubbles (drug uptake ratio = 4.60; 95% confidence interval [CI] = 1.70 to 12.47; P = .017) and unsonicated micelles (drug uptake ratio = 7.97; 95% CI = 3.72 to 17.08; P = .0032) and resulted in tumor regression in the mouse model.Multifunctional nanoparticles that are tumor-targeted drug carriers, long-lasting ultrasound contrast agents, and enhancers of ultrasound-mediated drug delivery have been developed and deserve further exploration as cancer therapeutics.
Modulation of constitutive nitric oxide synthase, bcl-2 and Fas expression in cultured human coronary endothelial cells exposed to anoxia–reoxygenation and angiotensin II: role of AT1 receptor activation
Authors: D Li
Journal: Cardiovascular Research (1999)

Background: Angiotensin II (Ang II) plays a critical role in the pathophysiology of myocardial ischemia–reperfusion injury. We have recently shown that reoxygenation following a period of anoxia causes apoptosis of cultured human coronary artery endothelial cells (HCAECs). Ang II further enhances apoptosis of HCAECs via Ang II type 1 receptor (AT1R) activation. Recent studies suggest an important role of constitutive nitric oxide synthase (cNOS), Fas and bcl-2 proteins in apoptosis. This study was designed to examine the modulation of cNOS, and Fas and bcl-2 expression in HCAECs during exposure to anoxia–reoxygenation and Ang II. Methods and Results: HCAECs were exposed to anoxia–reoxygenation and Ang II. Anoxia- reoxygenation significantly decreased cNOS mRNA, protein and activity in cultured HCAECs (P<0.05 vs. control). Anoxia–reoxygenation also caused an increase in Fas and a decrease in bcl-2 protein expression in cultured HCAECs (both P<0.05 vs. control). The presence of Ang II (0.3 μM) further enhanced these effects of anoxia–reoxygenation on cNOS, Fas and bcl-2 expression. The effects of Ang II were significantly attenuated by the AT1R inhibitor losartan (10 μM). Conclusion: During exposure of HCAECs to anoxia–reoxygenation and Ang II, AT1R activation induces important changes in cNOS mRNA, protein expression and activity, as well as bcl-2 and Fas protein expression which may have a bearing on the development of apoptosis.
Alveolar haemorrhage in anti-glomerular basement membrane disease without detectable antibodies by conventional assays
Authors: D J Serisier
Journal: Thorax (2006)

Anti-glomerular basement membrane (anti-GBM) disease represents the spectrum of disease attributable to circulating anti-GBM antibodies. While active anti-GBM disease in the absence of circulating anti-GBM antibodies has been described, it is considered rare with the use of current routinely available assays. We report four subjects with features consistent with active anti-GBM antibody disease without detectable antibodies by routinely available enzyme linked immunosorbent assay (ELISA) and immunoblot techniques. All were smokers who presented with diffuse alveolar haemorrhage, minimal renal involvement, and undetectable anti-GBM antibodies. Seronegative anti-GBM disease with predominant pulmonary involvement may be more common than previously appreciated and should be part of the differential diagnosis for otherwise unexplained diffuse alveolar haemorrhage. Renal biopsy with immunofluorescent studies should be considered in the diagnostic evaluation of such subjects, including those with idiopathic pulmonary haemosiderosis.
Systematic comparison of nonmelanoma skin cancer microarray datasets reveals lack of consensus genes
Authors: R. Van Haren, D. Feldman, A.A. Sinha
Journal: British Journal of Dermatology (2009)

Summary Background DNA microarray technology has revealed vast numbers of gene expression alterations associated with human malignancies. Assigning validity and biological significance to these changes, however, remains a considerable hurdle. Recently, microarray analysis has been applied to the study of nonmelanoma skin cancer. Objectives To compare experimental data rigorously in order to strengthen conclusions regarding the pathogenesis of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), and to evaluate systematically the experimental and statistical parameters that may impact the degree of consensus among differentially expressed genes (DEGs) between studies. Methods We performed a systematic comparison of 10 studies that applied DNA microarray technology to study BCC/SCC. Results A total of 1133 DEGs collectively reported across the studies were compared, and 64 DEG overlaps were found: 18 DEG overlaps in SCC vs. SCC study comparisons, 18 DEG overlaps in BCC vs. BCC study comparisons and 28 DEG overlaps in BCC vs. SCC study comparisons. We documented differences in several experimental methods that may account for the relative lack of consensus between studies, including sample type, tissue procurement/handling, microarray chip and statistical analysis. The two most dysregulated biological pathways across all studies involved genes with enzymatic and structural/adhesion functions. Conclusions DEGs that were found to overlap across two or more studies and biological pathways with the largest representation of DEGs across studies may be particularly relevant to disease pathogenesis and serve as targets for future therapy. In future work, more consistent experimental methods across laboratories may improve the validity of reported DEGs and strengthen conclusions drawn from microarray data.
Efficacy of nasal continuous positive airway pressure therapy in chronic heart failure: importance of underlying cardiac rhythm
Authors: J. L Kiely, P. Deegan, A. Buckley, P. Shiels, B. Maurer, W. T McNicholas
Journal: Thorax (1998)

Some previous reports have indicated beneficial cardiac effects of nasal continuous positive airway pressure (NCPAP) in patients with severe congestive heart failure (CHF), but others have reported deleterious cardiac effects, particularly among patients in atrial fibrillation (AF). The aim of this study was to determine if differences in cardiac rhythm influence the acute cardiac response to NCPAP.Eleven consecutive patients with CHF were recruited, six in atrial fibrillation (AF) and five with sinus rhythm (SR). Cardiac index was measured during awake NCPAP application by the thermodilution technique during cardiac catheterisation. NCPAP was applied in a randomised sequence at pressures of 0, 5, and 10 cm H2O with three 30 minute applications separated by 20 minute recovery periods without NCPAP.Significant differences were found between the AF and SR groups for cardiac index responses to NCPAP (p = 0.004, ANOVA) with a fall in cardiac index in the AF group (p = 0.02) and a trend towards an increase in the SR group (p = 0.10). Similar differences were seen between the groups in stroke volume index responses but not in heart rate responses. Changes in systemic vascular resistance were also significantly different between the two groups (p < 0.005, ANOVA), rising in the AF group but falling in the SR group.These data indicate an important effect of underlying cardiac rhythm on the awake haemodynamic effects of NCPAP in patients with CHF.
Release of Adrenal Catecholamines by Angiotensin II
Authors: MICHAEL J. PEACH, WILLIAM H. CLINE, DANIEL T. WATTS
Journal: Circulation Research (1966)

Several recent investigations have presented indirect evidence that angiotensin stimulates the release of adrenal medullary catecholamines. The following work was undertaken in an attempt to show in vivo angiotensin stimulation of the adrenal medulla by analysis of plasma catecholamines. Mongrel dogs, anesthetized with pentobarbital, were infused for 10 min with doses of 0.025, 0.05, and 0.1 µg per kg per min of angiotensin or injected with single doses of 0.5, 1.0 and 2.0 µg per kg. Blood samples were taken from the inferior vena cava (above the outflow from the adrenal veins) at the peak of the pressor responses to single doses or during and after the infusions. The samples were fluorometrically analyzed for epinephrine and norepinephrine. It was found that angiotensin produced an increase in circulating catecholamines. Epinephrine was significantly increased by infusions of 0.05 and 0.1 µg per kg per min and all three injected doses. Plasma norepinephrine was significantly increased also except with the 0.5 µg per kg injected dose of angiotensin. Angiotensin infusion of 0.025 µg per kg per min did not cause a detectable change in circulating catecholamine levels. In the infusion experiments, norepinephrine was more transiently increased than epinephrine. These results show that various pressor doses of angiotensin stimulate release of adrenal catecholamines.
Exosomes with major histocompatibility complex class II and co-stimulatory molecules are present in human BAL fluid
Authors: C. Admyre, J. Grunewald, J. Thyberg, S. Gripenbäck, G. Tornling, A. Eklund, A. Scheynius, S. Gabrielsson
Journal: European Respiratory Journal (2003)

Exosomes are 30–100 nm diameter vesicles formed by inward budding of endosomal compartments and are produced by several cell types, including T‐cells, B‐cells and dendritic cells (DC)s. Exosomes from DCs express major histocompatibility complexes (MHC) class I and II, and co-stimulatory molecules on their surface, and can induce antigen-specific activation of T‐cells. The aims of the present study were to investigate for the presence of exosomes in bronchoalveolar lavage fluid (BALF) from healthy individuals, and to establish if these exosomes bear MHC and co-stimulatory molecules. The authors analysed BALF taken from seven healthy volunteers and used exosomes from monocyte-derived DC (MDDC) cultures as a reference. After ultracentrifugation, exosomes were bound to anti‐MHC class II coated magnetic beads and analysed by flow cytometry and electron microscopy. The authors report for the first time that exosomes are present in BALF. These exosomes are similar to MDDC derived exosomes as they express MHC class I and II, CD54, CD63 and the co-stimulatory molecule CD86. The results demonstrate that exosomes are present in the lung, and since they contain both major histocompatibility complex and co-stimulatory molecules it is likely that they are derived from antigen presenting cells and might have a regulatory role in local immune defence.
Disruption of Cancer Cell Replication by Alternating Electric Fields
Authors: Eilon D. Kirson, Zoya Gurvich, Rosa Schneiderman, Erez Dekel, Aviran Itzhaki, Yoram Wasserman, Rachel Schatzberger, Yoram Palti
Journal: Cancer Research (2004)

Abstract Low-intensity, intermediate-frequency (100–300 kHz), alternating electric fields, delivered by means of insulated electrodes, were found to have a profound inhibitory effect on the growth rate of a variety of human and rodent tumor cell lines (Patricia C, U-118, U-87, H-1299, MDA231, PC3, B16F1, F-98, C-6, RG2, and CT-26) and malignant tumors in animals. This effect, shown to be nonthermal, selectively affects dividing cells while quiescent cells are left intact. These fields act in two modes: arrest of cell proliferation and destruction of cells while undergoing division. Both effects are demonstrated when such fields are applied for 24 h to cells undergoing mitosis that is oriented roughly along the field direction. The first mode of action is manifested by interference with the proper formation of the mitotic spindle, whereas the second results in rapid disintegration of the dividing cells. Both effects, which are frequency dependent, are consistent with the computed directional forces exerted by these specific fields on charges and dipoles within the dividing cells. In vivo treatment of tumors in C57BL/6 and BALB/c mice (B16F1 and CT-26 syngeneic tumor models, respectively), resulted in significant slowing of tumor growth and extensive destruction of tumor cells within 3–6 days. These findings demonstrate the potential applicability of the described electric fields as a novel therapeutic modality for malignant tumors.
Tumor necrosis factor/cachectin increases permeability of endothelial cell monolayers by a mechanism involving regulatory G proteins.
Authors: J Brett, H Gerlach, P Nawroth, S Steinberg, G Godman, D Stern
Journal: The Journal of Experimental Medicine (1989)

Endothelium is an important target of tumor necrosis factor/cachectin (TNF), a central mediator of the host response in endotoxemia and Gram-negative sepsis. In this report, TNF is shown to increase the permeability of endothelial cell monolayers to macromolecules and lower molecular weight solutes by a mechanism involving a pertussis toxin-sensitive regulatory G protein. Within 1-3 h of exposure to TNF (5 nM), changes in cell shape/cytoskeleton occurred that led to disruption of monolayer continuity with the formation of intercellular gaps. Correlated with these structural changes was an increase in endothelial permeability to macromolecular and lower molecular weight tracers; time-dependent, reversible increases in passage of these tracers, evident by 1-3 h, were observed after addition of TNF to cultures. Perturbation of barrier function by TNF also depended on the dose of TNF added being half-maximal by approximately 0.4 nM. Only a brief exposure (15 min) of TNF to endothelium was required to induce an increase in permeability, and this was not prevented by the presence of cycloheximide or actinomycin D. Preincubation of monolayers with pertussis toxin blocked in parallel TNF-induced increased passage of solutes and cell shape/cytoskeletal perturbation, indicating the close correlation between these changes in endothelial cell function. In contrast, pertussis toxin did not alter TNF-induced modulation of two endothelial cell coagulant properties. These data provide evidence for two intracellular pathways of TNF action that are distinguishable by pertussis toxin and provide insight into a mechanism underlying loss of solute from the intravascular space mediated by TNF: alteration in endothelial cell barrier function.
Imbalance Between Xanthine Oxidase and Nitric Oxide Synthase Signaling Pathways Underlies Mechanoenergetic Uncoupling in the Failing Heart
Authors: Walter F. Saavedra, Nazareno Paolocci, Marcus E. St. John, Michel W. Skaf, Garrick C. Stewart, Jin-Sheng Xie, Robert W. Harrison, Joshua Zeichner, Daniel Mudrick, Eduardo Marbán, David A. Kass, Joshua M. Hare
Journal: Circulation Research (2002)

Inhibition of xanthine oxidase (XO) in failing hearts improves cardiac efficiency by an unknown mechanism. We hypothesized that this energetic effect is due to reduced oxidative stress and critically depends on nitric oxide synthase (NOS) activity, reflecting a balance between generation of nitric oxide (NO) and reactive oxygen species. In dogs with pacing-induced heart failure (HF), ascorbate (1000 mg) mimicked the beneficial energetic effects of allopurinol, increasing both contractility and efficiency, suggesting an antioxidant mechanism. Allopurinol had no additive effect beyond that of ascorbate. Crosstalk between XO and NOS signaling was assessed. NOS inhibition with N G -monomethyl- l -arginine (L-NMMA; 20 mg/kg) had no effect on basal contractility or efficiency in HF, but prevented the +26.2±3.5% and +66.5±17% enhancements of contractility and efficiency, respectively, observed with allopurinol alone. Similarly, improvements in contractility and energetics due to ascorbate were also inhibited by L-NMMA. Because of the observed NOS-XO crosstalk, we predicted that in normal hearts NOS inhibition would uncover a depression of energetics caused by XO activity. In normal conscious dogs, L-NMMA increased myocardial oxygen consumption (MV̇O 2 ) while lowering left ventricular external work, reducing efficiency by 31.1±3.8% ( P &lt;0.005). Lowered efficiency was reversed by XO inhibition (allopurinol, 200 mg) or by ascorbate without affecting cardiac load or systemic hemodynamics. Single-cell immunofluorescence detected XO protein in cardiac myocytes that was enhanced in HF, consistent with autocrine signaling. These data show that both NOS and XO signaling systems participate in the regulation of myocardial mechanical efficiency and that upregulation of XO relative to NOS contributes to mechanoenergetic uncoupling in heart failure.