tbuckley/cabot-search huggingface dataset:
Catheter-Related Interventions to Prevent Peritonitis in Peritoneal Dialysis
Authors: Giovanni F.M. Strippoli, Allison Tong, David Johnson, Francesco P. Schena, Jonathan C. Craig
Journal: Journal of the American Society of Nephrology (2004)

As many as 15 to 50% of end-stage kidney disease patients are on peritoneal dialysis (PD), but peritonitis limits its more widespread use. Several PD catheter–related interventions (catheter designs, surgical insertion approaches, and connection methods) have been purported to reduce the risk of peritonitis in PD. The goal was to assess the trial evidence supporting their use. The Cochrane CENTRAL Registry, MEDLINE, EMBASE, and reference lists were searched for randomized trials of catheter types and related interventions in PD. Two reviewers extracted data on the rates of peritonitis and exit-site/tunnel infection, catheter removal/replacement, technique failure, and all-cause mortality. Analysis was by a random effects model, and results are expressed as relative risk and 95% confidence intervals. Thirty-seven eligible trials (2822 patients) were identified: eight of surgical strategies of catheter insertion, eight of straight versus coiled catheters, 10 of Y-set versus conventional spike systems, four of Y-set versus double-bag systems, and seven of other interventions. Despite the large total number of patients, few trials covered the same interventions, small numbers of patients were enrolled in each trial, and the methodologic quality was suboptimal. Y-set and twin-bag systems were superior to conventional spike systems (seven trials, 485 patients; relative risk, 0.64; 95% confidence intervals 0.53 to 0.77), and no other catheter-related intervention was demonstrated to prevent peritonitis in PD. This systematic review demonstrates that of all catheter-related interventions designed to prevent peritonitis in PD, only disconnect (twin-bag and Y-set) systems have been proved to be effective (compared with conventional spike systems). Despite the importance of PD as a renal replacement therapy modality and the large number of patients who receive it, it is still not known whether any particular PD catheter designs, implantation techniques, or modalities are effective, given the limitations of available trials.
The GRID: The General Repository for Interaction Datasets
Authors: Bobby-Joe Breitkreutz, Chris Stark, Mike Tyers
Journal: Genome biology (2003)

We have developed a relational database, called the General Repository for Interaction Datasets (The GRID; http://biodata.mshri.on.ca/grid) to archive and display physical, genetic and functional interactions. The GRID displays data-rich interaction tables for any protein of interest, combines literature-derived and high throughput interaction datasets, and is readily accessible via the World Wide Web. Interactions parsed in the GRID can be viewed in graphical form with a versatile visualization tool called Osprey.
Increased prevalence of methylenetetrahydrofolate reductase C677T variant in patients with inflammatory bowel disease, and its clinical implications
Authors: N Mahmud, A Molloy, J McPartlin, R Corbally, A S Whitehead, J M Scott, D G Weir
Journal: Gut (1999)

Inflammatory bowel disease (IBD) is associated with an increased incidence of thromboembolic disease. Hyperhomocysteinaemia (hyper-tHcy), a condition associated with the C677T variant of 5, 10-methylenetetrahydrofolate reductase (MTHFR), is linked with an increased incidence of thromboembolic disease. Hyper-tHcy has been reported in patients with IBD.To assess the prevalence of the C677T MTHFR genotype and the contribution of this genotype to hyper-tHcy in patients with IBD.Patients with established IBD (n=174) and healthy controls (n=273) were studied. DNA samples were genotyped for the MTHFR (C677T) mutation. Subjects were categorised as homozygous for the thermolabile variant (TT), heterozygous for wild type and variant (CT), or homozygous for the wild type (CC).Plasma homocysteine concentrations were significantly higher in patients with IBD than in healthy controls. A total of 17.5% of ulcerative colitis and 16.8% of Crohn's disease patients were homozygous for the C677T variant compared with 7.3% of controls. Homozygosity (TT) for the variant was associated with higher plasma tHcy levels in patients with IBD and in healthy controls. When all subjects who were TT for the variant were excluded, median plasma tHcy was still significantly higher in IBD than controls. Plasma vitamin B(12) levels were lower in patients with IBD irrespective of MTHFR genotype.There is an association between the thermolabile MTHFR C677T variant and IBD. This accounts in part for the raised plasma tHcy found in patients with IBD and may contribute to the increased incidence of thromboembolic complications. All patients with IBD should receive low dose folic acid and vitamin B(12) therapy to protect against the thromboembolic complications of raised tHcy.
Pressure tension, and force of closure of the human lower esophageal sphincter and esophagus.
Authors: P Biancani, M P Zabinski, J Behar
Journal: Journal of Clinical Investigation (1975)

The mechanical characteristics of the circular muscle of the human lower esophageal sphincter and esophagus were studied in subjects with competent and incompetent sphincters. Pressure-diameter curves were constructed by producing various degrees of circumferential stretch with pressure-measuring probes of increasing diameter. The circumferential membrane tension (force of closure) and the circumferential stress (muscle tension) of the circular muscle layer were also calculated from these data. The pressure-diameter curves of competent and incompetent sphincters were different in magnitude and shape. Incompetent sphincters had lower pressures at all diameters, with pressure gradually increasing with larger probe diameter. In contrast for competent sphincters the pressure was highest near closure, with an initial decline and then an increase in pressure with increasing probe diameter. Both shape and magnitude of pressure-diameter curves of competent and incompetent sphincters were interchangeable when manipulated by pharmacologic agents. Urecholine increased the pressures and changed the incompetent pressure-diameter curve to the levels of the competent sphincter; conversely. Pro-Banthine decreased pressures and changed the shape of the competent pressure-diameter curve to the levels of the incompetent sphincter. Force of closure and circular muscle tension curves of competent and incompetent sphincters were similar in shape but were higher at all diameters for competent sphincters. Force of closure and circular muscle tension increased with larger probe diameter. However, the diameter of optimal tension development was larger than the largest probe used and certainly far from closure. Fundoplication increased the magnitude and changed the shape of the incompetent pressure-diameter curve to one similar to a competent curve. This pressure change was associated with an increase in the force of closure, suggesting that fundopliation modified the length-force of closure characteristics of the incompetent spincter.
The Effect of Augmentation Therapy on Bronchial Inflammation in <b>α</b>1-Antitrypsin Deficiency
Authors: Robert A. Stockley, Darren L. Bayley, Ipek Unsal, Lee J. Dowson
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

α1-Antitrypsin (AAT) deficiency predisposes to bronchitis and emphysema associated with neutrophilic airway inflammation. The efficacy of augmentation therapy has not been proven clinically or by demonstrating an effect on airway inflammation. We treated 12 patients with four infusions of Prolastin (60 mg/kg) at weekly intervals and monitored both the serum and secretion concentrations of AAT as well as markers of neutrophilic inflammation, including myeloperoxidase, elastase, and the neutrophil chemoattractants interleukin-8 and leukotriene B4. Serum AAT rose and was maintained above the protective threshold. In addition, AAT concentrations in the sputum rose from a mean of 0.17 μM (SEM ± 0.04) before therapy to concentrations similar to nondeficient subjects (0.43 ± 0.12) 1 week after the first infusion (p < 0.01). This was associated with a reduction in elastase activity (p < 0.002) and the chemoattractant leukotriene B4 (p < 0.02), which fell from a median baseline value of 13.46 nM (range, 4.17–55.00) to 8.62 nM (4.23–21.59) the day following the last infusion. Although median values for myeloperoxidase and interleukin-8 also fell, the changes failed to achieve statistical significance. In summary, short-term therapy with AAT increased lung secretion concentrations and was associated with a fall in leukotriene B4, which is thought to be central to the airway inflammation of AAT deficiency.
Interleukin-12 Deficiency Is Permissive for Angiogenesis in UV Radiation-Induced Skin Tumors
Authors: Syed M. Meeran, Suchitra Katiyar, Craig A. Elmets, Santosh K. Katiyar
Journal: Cancer Research (2007)

Abstract We have shown previously that endogenous deficiency of interleukin (IL)-12 promotes photocarcinogenesis in mice. To characterize the role of IL-12 deficiency in tumor angiogenesis, we developed IL-12p35 knockout (IL-12 KO) mice on a C3H/HeN background. IL-12 KO mice and their wild-type (WT) counterparts were subjected to a photocarcinogenesis protocol. When tumor yield was stabilized, samples of tumor and tumor-uninvolved UVB-exposed skin were collected and subjected to immunohistochemistry, gelatinolytic zymography, real-time PCR, and Western blot analysis of angiogenic factors. We found that the protein, mRNA expression and/or activity of the matrix metalloproteinases (MMP)-2, MMP-3, MMP-7, and MMP-9, and basic fibroblast growth factor, which play crucial roles in tumor growth, were significantly higher in UVB-exposed skin and tumors of IL-12 KO mice compared with WT mice. With respect to the tumor vasculature, the expression of CD31-positive cells and the expression of vascular endothelial growth factor were higher in the tumors of IL-12 KO mice than WTs. The proliferative capacity of tumor cells of the IL-12 KO mice was significantly higher than their WT counterparts when determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and by analyzing the expression of cyclin D1. The level of the proinflammatory cytokine IL-6 and the expression of IL-23 in tumors of IL-12 KO mice were markedly higher than in the tumors of WT mice. IL-23 has been shown to promote tumor growth. Together, these data indicate for the first time that IL-12 deficiency promotes proangiogenic stimuli in UVB-induced skin tumors and suggest that endogenous enhancement of IL-12 levels may be effective in the prevention and treatment of UV-induced skin cancers. [Cancer Res 2007;67(8):3785–93]
Protection by hypoxic preconditioning against hypoxia-reoxygenation injury in guinea-pig papillary muscles
Authors: Y Kasamaki
Journal: Cardiovascular Research (1997)

Objective: Developed tension in guinea-pig papillary muscles is depressed by prolonged hypoxia; subsequent reoxygenation leads to a partial recovery that stabilizes after an early period of arrhythmia. We have investigated whether hypoxic preconditioning in these muscles (1) improves the recovery of developed tension, (2) protects against reoxygenation arrhythmia, and (3) causes other significant electromechanical changes. Methods: Papillary muscles stimulated at 1 Hz were superfused with oxygenated Krebs solution for 60 min and either preconditioned (5 min of 3 Hz pacing under substrate-free hypoxic conditions, 10 min of normoxic recovery) or equilibrated for an extra 15 min. Muscles were subsequently challenged with substrate-free hypoxia (1 Hz), and reoxygenated (1 Hz) for 60 min. Contractile performance, action potential parameters, and indicators of arrhythmic activity were measured in 10 preconditioned and 10 non-preconditioned muscles. Results: Developed tension in preconditioned muscles declined to the same level (10–15% control) as in non-preconditioned muscles after 60 min hypoxia. A notable difference was that developed tension in the preconditioned muscles failed to rebound during mid-hypoxia, a hallmark feature in non-preconditioned muscles. The action potential duration and overshoot collapsed at a significantly faster rate in hypoxic preconditioned muscles. Action potential recovery during reoxygenation was similar in the two groups of muscles, but recovery of developed tension was significantly stronger in preconditioned (76.7±5.4%) than in non-preconditioned (42.9±1.7%) muscles (P<0.001). Reoxygenation provoked arrhythmic activity in all muscles, but the summed average duration was shorter (5.5±1.0 vs. 9.4±1.5 min) (P<0.05) in the preconditioned muscles. Conclusions: Hypoxic preconditioning can significantly enhance post-hypoxia recovery of developed tension, and significantly attenuate arrhythmic activity, in guinea-pig papillary muscles. © 1997 Elsevier Science B.V.
Minimizing Hemodialysis Vascular Access Trauma with an Improved Needle Design
Authors: EDWARD A. ROSS, JILL W. VERLANDER, LILIA C. KOO, IRVIN F. HAWKINS
Journal: Journal of the American Society of Nephrology (2000)

Abstract. The maintenance and longevity of hemodialysis vascular access remains one of the most problematic topics in the care of dialysis patients. Although much attention has focused on neointimal hyperplasia, the repetitive trauma to vessel walls by dialysis needles causes significant cumulative damage that has undergone little investigation. Commercial needles have beveled tips with intentional cutting surfaces to ease insertion. It was hypothesized that a pencil-point conical-shaped needle would cause less damage by taking advantage of the elasticity of native fistulae and produce an improved hole configuration in synthetic materials with minimal ability to stretch. A needle was subsequently designed with a removable pencil-point trocar and a side arm for the dialysis tubing. Once the trocar is removed, the blunt-ended cannula can be advanced or can be subject to inadvertent motion without causing damage to the luminal surface of the access. The new design as well as standard 15-gauge hemodialysis needles were tested on Gore-Tex ® graft material and two bovine carotid artery preparations. Scanning electron microscopy was used to study the hole patterns. For all materials, the commercial needle holes had typical crescent shapes, and the cuts sliced sequentially through the various layers. For grafts, the new design caused a linear defect parallel to the axis of the graft that may preserve longitudinal strength. Interestingly, that tear line was nearly perpendicular to the linear hole in the thin polytetrafluoroethylene overwrap, which would be consistent with maintenance of hoop integrity. It is believed that these nonoverlapping defects would also improve hemostasis. The bovine specimens tested the importance of tissue stretching: Fresh carotid artery had experimental holes dramatically smaller than those from standard needles. In the denatured tissue, the experimental needle provided less benefit than that observed in fresh tissue, which is likely due to limited elasticity of the preserved artery. Improvement in needle design thus provides distinct advantages for native vessels and unique less traumatic holes in current synthetic materials. Pencil-point needle designs may be particularly applicable to the development of new elastomeric graft material.
Regulation of Endothelial Production of C-Type Natriuretic Peptide in Coculture With Vascular Smooth Muscle Cells
Authors: Yasato Komatsu, Hiroshi Itoh, Shin-ichi Suga, Yoshihiro Ogawa, Norio Hama, Ichiro Kishimoto, Osamu Nakagawa, Toshio Igaki, Kentaro Doi, Takaaki Yoshimasa, Kazuwa Nakao
Journal: Circulation Research (1996)

Abstract Recently, we have demonstrated that C-type natriuretic peptide (CNP) is produced in vascular endothelial cells (ECs). In the present study, we investigated the interaction of ECs and vascular smooth muscle cells (SMCs) for endothelial production of CNP and its action on vascular growth, using the EC/SMC coculture system. The concentration of CNP-like immunoreactivity in the medium was increased 60-fold within 48 hours in the EC/SMC coculture with direct contact compared with that in EC alone. Northern blot analysis revealed the augmented expression of CNP mRNA in the EC/SMC coculture. The accumulation of intracellular cGMP in the coculture was concomitantly increased, and this response was blocked by anti-CNP monoclonal antibody and HS-142-1, a nonpeptide atrial natriuretic peptide receptor antagonist. The concentration of biologically active transforming growth factor-β (TGF-β) in the culture medium of the coculture with direct contact of ECs and SMCs was elevated to the level to stimulate endothelial production of CNP. Actually, the neutralizing antibody against TGF-β abrogated the cGMP accumulation in the coculture. These results show that endothelial production of CNP in the EC/SMC coculture is at least in part regulated by TGF-β. Furthermore, the conditioned medium from ECs stimulated by TGF-β was demonstrated to have a growth-inhibitory effect on SMCs, which was abolished by anti-CNP monoclonal antibody and HS-142-1. The treatment with anti-CNP monoclonal antibody and HS-142-1 also significantly increased the cell number of the EC/SMC coculture. The present study reveals the pathophysiological significance of endothelial CNP as a paracrine/autocrine vascular regulator for vascular growth in the interaction of ECs and SMCs.
Mechanisms of genetic resistance to Friend virus leukemia in mice. II. Resistance of mitogen-responsive lymphocytes mediated by marrow-dependent cells.
Authors: V Kumar, M Bennett
Journal: The Journal of Experimental Medicine (1976)

Friend leukemia virus suppresses the proliferative responses of normal thymus-dependent (T) and bursa equivalent-dependent (B) lymphocytes from spleen, thymus, lymph node, and bone marrow to mitogens. The suppressive effect of Friend virus complex (FV) requires fully infectious virions. Friend erythroleukemic cells, washed to removed extracellular virus, fail to suppress concanavalin A (Con-A)-induced mitogenesis of normal spleen cells. This indicates that FV does not mediate its immunosuppressive effect via transformed erythropoietic cells. The in vitro suppressive effect of FV on lymphocyte mitogenesis is under host genetic control. Spleen, bone marrow, and thymus cells from strains of mice susceptible to FV-induced leukemogenesis in vivo were quite susceptible to the suppressive effects of FV in vitro. On the other hand, similar cells from strains of mice such as C57BL/6 resistant to Friend erythroleukemia, were quite resistant to in virto immunosuppression by FV. Mitogenesis of splenic T cells from resistant B6 mice, previously treated with 89Sr, became susceptible to suppression by FV. This indicated that the in vitro resistance of lymphocytes to FV-induced suppression is not an intrinsic property of T cells, but is controlled by marrow-dependent (M) cells which are selectively eliminated by treatment with 89Sr. M-cell function does not develop in mice less than 3-wk old. The Con A response by thymus cells from 2-wk-old B6 mice was susceptible to suppression by FV, further supporting the concept that M cells may regulate the genetic resistance to FV.
Inhibition of the pentose phosphate pathway decreases ischemia–reperfusion-induced creatine kinase release in the heart
Authors: C Zuurbier
Journal: Cardiovascular Research (2004)

The oxidative pentose phosphate pathway (oxPPP) produces NADPH, which can be used to maintain glutathione in its reduced state (anti-oxidant; beneficial effects) or to produce radicals or nitric oxide (NO) through NADPH oxidase/NO synthase (detrimental effects). Changes in cytosolic redox status have been implicated in ischemic preconditioning (PC). This study investigates whether (1) PC affects mitochondrial redox state, (2) the oxPPP plays a protective or detrimental role in ischemia (I)-reperfusion (R) injury in the intact heart and (3) PPP is altered with PC.Isolated rat hearts were subjected to 40-min global I and 30-min R (CO, control). Ischemia was either preceded by three 5-min I/R periods (PC) and/or oxPPP inhibition by 6-aminonicotinamide (6AN) or NADPH oxidase/NO synthase inhibition by diphenyleneiodonium (DPI). NADH videofluorometry was used to determine mitochondrial redox state. PPP intermediates were determined in CO and PC hearts using tandem mass spectrometry.PC reduced ischemic damage (creatine kinase, CK, release from 337+/-64 to 147+/-41 U/R/gdw) and contracture (from 59+/-5 to 31+/-3 mm Hg) and increased recovery of contractility (from 48+/-10% to 88+/-8%), as compared to CO. PC was without effect on NADH fluorometry. Inhibition of the oxPPP reduced injury (CK release: 91+/-24 U/R/gdw) to similar levels as PC, without improving contractility. Inhibition of NADPH oxidase/NO synthase mimicked the effects of oxPPP inhibition on injury (CK release: 140+/-22 U/R/gdw). Although levels of ribose-5P and (ribulose-5P+xylulose-5P) rose several fold during ischemia with minor changes in sedoheptulose-7P, demonstrating an active PPP in the heart, PC did not affect these levels.(1) PC can attenuate cardiac reperfusion injury without alterations in mitochondrial redox state; (2) inhibition of the oxPPP protects the heart against I/R-induced CK release; and (3) PC does not result in altered activity of the PPP.