tbuckley/cabot-search huggingface dataset:
Controlled trial of anti-tuberculous chemotherapy for two years in Crohn's disease.
Authors: G L Swift, E D Srivastava, R Stone, R D Pullan, R G Newcombe, J Rhodes, S Wilkinson, P Rhodes, G Roberts, B W Lawrie
Journal: Gut (1994)

One hundred and thirty patients with active symptoms of Crohn9s disease were treated in a double blind randomised controlled trial with rifampicin, isoniazid, and ethambutol, or identical placebos for up to two years. All other treatment considered necessary was continued. Analyses were based on 126 patients, 63 in each treatment group. Thirty seven in the active and 30 in the placebo group had previous surgical procedures. There was no difference in concomitant treatment between the two groups. Thirty in the active and 46 in the placebo groups were taking corticosteroids at entry to the trial. Forty eight of 63 patients in the active and 49 of 63 in the placebo group, completed at least 12 months9 therapy. Reasons for early withdrawal included pregnancy, adverse reaction, and failure to comply. There was no significant difference in the mean number of months completed between the two groups. Nineteen adverse reactions were recorded for 17 patients in the active group compared with three reactions in patients on placebo. All of the nine patients withdrawn early because of adverse reactions were in the active group. Fifteen patients on active treatment and 14 on placebo had surgery during the trial with no difference in the type of surgery required between the groups. Radiological assessments based on 98 patients at the end of the trial showed no significant differences between groups in changes of extent of disease. More patients developed strictures on placebo compared with active treatment but without a statistically significant difference. No differences were found between groups for the total prednisolone dose or the number of days on which prednisolone dose was 10 mg or above. Serial measurements of body weight and Crohn9s disease activity index (CDAI) together with blood values for albumin, haemoglobin, white cell count, and platelets showed no consistent different differences between groups. There were occasional significant differences for some of these values between groups, which were not sustained. The trail provides little evidence of tangible benefit from the trail treatment.
Bronchoscopic diagnosis of sarcoidosis
Authors: C Leonard, VJ Tormey, C O'Keane, CM Burke
Journal: European Respiratory Journal (1997)

Transbronchial lung biopsy (TBLB), transbronchial needle aspiration (TBNA) of mediastinal lymph nodes and bronchoalveolar lavage (BAL) are routinely performed at fibreoptic bronchoscopy. Up to the present time, no data have been available on the efficacy of performing all three of these procedures simultaneously in the bronchoscopic work-up of sarcoidosis. A prospective study was undertaken to compare the diagnostic yield from TBLB, TBNA and BAL in patients presenting with clinical and radiological features typical of sarcoidosis. Thirteen consecutive patients with clinical and radiological features consistent with stage I and II sarcoidosis underwent bronchoscopy with TBLB, TBNA and BAL. Noncaseating granulomata (stain and culture negative for tuberculosis bacilli and fungi) were found in seven of the 13 patients by TBLB, and in six of the 13 patients by TBNA (of which four patients had negative TBLB). Eight of the 13 patients had classical "sarcoid" BAL findings, i.e. &gt;12% lymphocytes, and high CD4+:CD8+ lymphocyte ratio. Combining TBLB, TBNA and BAL gave a diagnostic sensitivity of 100% (12 out of 12 patients) for sarcoidosis. The remaining patient had nondiagnostic bronchoscopic studies and mediastinoscopy biopsy showed a non-Hodgkin's lymphoma. Our data suggest that performing simultaneous transbronchial lung biopsy, transbronchial needle aspiration and bronchoalveolar lavage produces optimal results in the diagnosis of sarcoidosis.
Migration of monocytes across endothelium and passage through extracellular matrix involve separate molecular domains of PECAM-1.
Authors: F Liao, H K Huynh, A Eiroa, T Greene, E Polizzi, W A Muller
Journal: The Journal of Experimental Medicine (1995)

During the inflammatory response, the adhesion molecule PECAM plays a crucial role in transendothelial migration, the passage of leukocytes across endothelium. We report here an additional role for PECAM in the subsequent migration of monocytes through the subendothelial extracellular matrix. PECAM has six immunoglobulin (Ig) superfamily domains. Monoclonal antibodies whose epitopes map to domains 1 and/or 2 selectively block monocyte migration through the endothelial junction, whereas those that map to domain 6 block only the migration through the extracellular matrix, trapping the monocyte between the endothelium and its basal lamina. Therefore, transendothelial migration (diapedesis) and passage through extracellular matrix (interstitial migration) are distinct and separable phases of monocyte emigration. Furthermore, distinct and separate Ig domains of PECAM are involved in mediating these two steps.
Immunomodulatory Effects of Statins
Authors: Wulf Palinski, Sotirios Tsimikas
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Clinical trials with statins have demonstrated a marked reduction of cardiovascular mortality. However, it remains controversial whether these clinical benefits stem from powerful cholesterol-lowering effects of statins or whether they are due in part to their cholesterol-independent effects on vascular function, plaque growth, plaque rupture, or thrombosis. The identification of several mechanisms through which statins decrease the recruitment of monocytes and T cells into the arterial wall and inhibit T cell activation and proliferation <i>in vitro</i> have prompted speculations that immunomodulatory effects of statins may be beneficial in recipients of organ transplants. Hypercholesterolemia is frequent in these patients, and delayed-type hypersensitivity reactions in the arterial walls of the graft may be compounded by chronic inflammation associated with conventional atherogenesis. To assess the potential clinical relevance of immunomodulatory effects of statins, the role of the immune system in atherogenesis and the effects of statins <i>in vitro</i> in experimental models and in clinical trials will be reviewed. It is concluded that despite solid <i>in vitro</i> evidence, clinical evidence for an independent immunosuppressive effect of statins in organ transplant patients is presently insufficient; however, further investigation of their <i>in vivo</i> occurrence and clinical relevance is warranted.
Noninvasive Quantification of Left-to-Right Shunt in Pediatric Patients
Authors: Philipp Beerbaum, Hermann Körperich, Peter Barth, Hermann Esdorn, Jürgen Gieseke, Hans Meyer
Journal: Circulation (2001)

Background —Blood flow can be quantified noninvasively by phase-contrast cine MRI (PC-MRI) in adults. Little is known about the feasibility of the method in children with congenital heart disease. Methods and Results —In 50 children (mean age 6.2 years, range 1.1 to 17.7 years) with an atrial- or ventricular-level shunt, blood flow rate in the great vessels was determined by PC-MRI, and the ratio of pulmonary to aortic flow (Q̇p/Q̇s) was compared with Q̇p/Q̇s by oximetry. We found a difference of 2% and a range of −20% to +26% (limits of agreement, mean±2 SD). In another 7 children with congenital heart disease but no cardiac shunting (mean age 7.9 years, range 1.3 to 13.5 years), Q̇p/Q̇s by PC-MRI was 1.02 (SD ±0.06). No difference between systemic venous and aortic flow volumes was found (range −17% to +20%, n=37). Blood flow through a secundum atrial septal defect as assessed by PC-MRI (n=24) overestimated the shunt compared with the difference between pulmonary and aortic flows. The mean difference between 3 repeated PC-MRI measurements in each location was 5.3% (SD ±4.0%, n=522), demonstrating good precision. The interobserver variability was low. The accuracy of PC-MRI was confirmed by in vitro experiments. Conclusions —Determination of Q̇p/Q̇s by PC-MRI in children is quick, safe, and reliable compared with oximetry. Systemic venous flow can be quantified by PC-MRI, whereas through-plane shunt measurement within an atrial septal defect is inaccurate.
Association between Multidisciplinary Care and Survival for Elderly Patients with Chronic Kidney Disease
Authors: Brenda R. Hemmelgarn, Braden J. Manns, Jianguo Zhang, Marcello Tonelli, Scott Klarenbach, Michael Walsh, Bruce F. Culleton
Journal: Journal of the American Society of Nephrology (2007)

The effectiveness of multidisciplinary care (MDC) in improving health outcomes for patients with chronic kidney disease (CKD) is uncertain. This study sought to determine the association among MDC, survival, and risk for hospitalization among elderly outpatients with CKD. A total of 6978 patients who were 66 yr and older and had CKD were identified between July 1 and December 31, 2001, and followed to December 31, 2004; 187 (2.7%) were followed in an MDC clinic. Logistic regression was used to determine the propensity score (probability of MDC) for each patient, and MDC and non-MDC patients then were matched 1:1 on the basis of their score. A Cox model was used to determine the association between MDC and risk for death and hospitalization. After adjustment for age, gender, baseline GFR, diabetes, and comorbidity score, there was a 50% reduction in the risk for death for the MDC compared with the non-MDC group (hazard ratio [HR] 0.50; 95% confidence interval [CI] 0.35 to 0.71). There was no difference in the risk for all-cause (HR 0.83; 95% CI 0.64 to 1.06) or cardiovascular-specific hospitalization (HR 0.76; 95% CI 0.54 to 1.06) for the MDC compared with the non-MDC group. In conclusion, it was found that MDC was associated with a significant reduction in the risk for all-cause mortality and, although not statistically significant, a trend toward a reduction in risk for all-cause and cardiovascular-specific hospitalizations. The benefits of MDC and an assessment of their economic impact should be tested in a randomized, controlled trial.
Dissemination of evidence-based clinical practice guidelines for hepatocellular carcinoma among Japanese hepatologists, liver surgeons and primary care physicians
Authors: N. Kokudo, Y. Sasaki, T. Nakayama, M. Makuuchi
Journal: Gut (2007)

exist.It is, therefore, likely that not only rats, but every species, including humans, exposed to long-term hypergastrinaemia is at risk of developing ECL cell carcinoids.3. Role of the ECL cell in gastric cancer.Kuipers does not discuss the role of the ECL cell in gastric carcinogenesis.It is now apparent that a higher proportion of gastric carcinomas than previously realised are probably neuroendocrine carcinomas. 1 5 Moreover, most of these neuroendocrine carcinomas develop from the predominant neuroendocrine cell in the stomach, the ECL cell. 1 In addition, gastric ECL cell carcinoids secondary to hypergastrinaemia may progress to neuroendocrine carcinomas. 1 The gastric carcinomas developing in patients with pernicious anaemia most often originate in the oxyntic area, indicating that the lack of acidity is not the most important factor in gastric carcinogenesis in these patients, and that the ECL cell is probably the cell of origin in these carcinomas. 1 It should also be recalled that the carcinogenic effect of Helicobacter pylori infection may be related to hypergastrinaemia. 1To conclude, PPI treatment induces hypergastrinaemia.Long-term hypergastrinaemia predisposes to ECL cell tumours, such as ECL cell carcinoids and ECL cell neuroendocrine carcinomas.Long-term PPI treatment might, therefore, increase the risk of gastric cancer.It should be remembered that carcinogenesis is a long-term process often taking decades.
Association between the angiotensin-converting enzyme-insertion/deletion polymorphism and diabetic nephropathy
Authors: R Kunz, J P Bork, L Fritsche, J Ringel, A M Sharma
Journal: Journal of the American Society of Nephrology (1998)

Recent studies have implicated a variant of the angiotensin-converting enzyme gene (ACE), associated with increased activity of this enzyme, in the development and progression of diabetic nephropathy. This study provides a systematic review of all cross-sectional, case-control, and cohort studies in patients with insulin-dependent (IDDM) or non-insulin-dependent (NIDDM) diabetes mellitus of any race, examining the relationship between the ACE-insertion/deletion polymorphism and nephropathy. Nineteen studies in 21 populations published between 1994 and 1997 presenting data on 5336 patients were reviewed. Two investigators independently assessed the studies on methodologic quality, performance of study, and association between the ACE-insertion/deletion polymorphism and nephropathy. Separate analyses of the relationship between genotype and allele frequencies were performed for patients with IDDM and NIDDM by race, using Peto's odds ratio. In Caucasians with IDDM, pooling was not performed due to heterogeneity of the studies, but among the homogeneous studies, no association was detected. Likewise, no association was observed in Caucasian patients with NIDDM (odds ratio [OR], 1.10; 95% confidence interval [95% CI], 0.83 to 1.45). In Asian patients with NIDDM, the risk of nephropathy was increased in the presence of the DD or ID genotype (OR, 1.88; 95% CI, 1.42 to 2.85). Although this analysis fails to confirm an association between the ACE-insertion/deletion genotype and nephropathy in Caucasians with NIDDM or IDDM, a role for this genetic marker in Asian patients cannot be ruled out. However, due to methodologic limitations of individual studies, no definite conclusions can be drawn from this analysis. Clearly, more rigorous methodology needs to be applied in future studies.
Ozone-induced decrements in FEV1 and FVC do not correlate with measures of inflammation.
Authors: J R Balmes, L L Chen, C Scannell, I Tager, D Christian, P Q Hearne, T Kelly, R M Aris
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

In order to test the hypothesis that changes in lung function induced by ozone (O3) are correlated with cellular and biochemical indices of respiratory tract injury/inflammation, we exposed 20 healthy subjects, on separate days, to O3 (0.2 ppm) and filtered air for 4 h during exercise. Symptom questionnaires were administered before and after exposure, and pulmonary function tests (FEV1, FVC, and SRaw) were performed before, during, and immediately after each exposure. Fiberoptic bronchoscopy, with isolated left main bronchus proximal airway lavage (PAL) and bronchoalveolar lavage (BAL; bronchial fraction, the first 10 ml of fluid recovered) of the right middle lobe, was performed 18 h after each exposure. The PAL, bronchial fraction, and BAL fluids were analyzed for the following end points: total and differential cell counts, and total protein, fibronectin, interleukin-8 (IL-8), and granulocyte-macrophage colony-stimulating factor (GM-CSF) concentrations. The study population was divided into two groups, least-sensitive (n = 12; mean O3-induced change in FEV1 = -7.0%) and most-sensitive (n = 8; mean O3-induced change in FEV1 = -36.0%). We found a significant O3 effect on SRaw (p<0.001) and lower respiratory symptoms (p<0.001) for all subjects combined, but no significant differences between the least- and most-sensitive groups. Ozone exposure increased significantly percent neutrophils in PAL (p=0.01); percent neutrophils, total protein, and IL-8 in bronchial fraction (p<0.001, p<0.001, and p<0.01, respectively); and percent neutrophils, total protein, fibronectin, and GM-CSF in BAL (p<0.001, p<0.001, p<0.01, p=0.05, respectively) for all subjects combined; there were no significant differences, however, between least- and most-sensitive groups. Our results indicate that levels of O3-induced symptoms and respiratory tract injury/inflammation were not correlated with the magnitude of decrements in FEV1 and FVC.
Selective dye and ionic permeability of gap junction channels formed by connexin45.
Authors: R D Veenstra, H Z Wang, E C Beyer, P R Brink
Journal: Circulation Research (1994)

Gap junctions are thought to mediate the direct intercellular coupling of adjacent cells by the gating of an aqueous pore permeable to ions and molecules of up to 1 kD or 8 to 14 A in diameter. We performed ion-substitution and dye-transfer experiments to determine the relative Cl-/K+ conductance and dye permeability of anionic fluorescein derivatives in chick connexin45 (Cx45) channels. We demonstrate that Cx45 forms a 26 +/- 6-picosiemen (pS) channel with a maximum detectable Cl- permeability of 0.2 relative to K+ or Cs+. Although homogeneous channel conductances were observed in multichannel recordings, the open probability estimates were indicative of nonhomogeneous gating behavior and occasional cooperativity. A second conductance state of 19 +/- 4 pS begins to predominate at higher voltages. Cx45 gap junctions are permeable to 2',7'-dichlorofluorescein but are not permeable to the more polar 6-carboxyfluorescein dye. These observations suggest that the Cx45 pore diameter is approximately 10 A and is associated with a fixed negative charge within the junctional channel.
Evaluation of pharmacokinetics and pharmacodynamics relationships for Salvianolic Acid B micro-porous osmotic pump pellets in angina pectoris rabbit
Authors: Shu-Ling Kan, Jin Li, Jian-Ping Liu, Hong-Liang He, Wen-Jing Zhang
Journal: Asian Journal of Pharmaceutical Sciences (2014)

The work aims to investigate the in vitro release, pharmacokinetics (PK), pharmacodynamics (PD) and PK–PD relationships of Salvianolic Acid B micro-porous osmotic pump pellets (SalB-MPOPs) in angina pectoris New Zealand White (NZW) rabbits, compared with those of SalB immediate-release pellets (SalB-IRPs). The SalB plasma concentrations and Superoxide dismutase levels (PD index) were recorded continuously at predetermined time interval after administration, and the related parameters were calculated by using WinNonlin software. The release profile of MPOPs was more sustained than that of IRPs. PK results indicated that the mean C max was significantly lower, the SalB plasma concentrations were steadier, both area under concentration-time curve from 0 to 24 h (AUC 0–24 h ) and from 0 to infinity (AUC 0–∞ ) were presented larger, and both the peak concentration time ( T max ) and mean residence time (MRT) were prolonged for MPOPs, as compared with those of IRPs. PD results suggested that peak drug effect ( E max ) was lower and the equilibration rate constant ( k e0 ) between the central compartment and the effect compartment was higher of MPOPs vs. those of IRPs. PK–PD relationships demonstrated that the effect-concentration-time (ECT) course of MPOPs was clockwise hysteresis loop, and that of IRPs was counter-clockwise hysteresis loop. Collectively, those results demonstrated that MPOPs were potential formulations in treating angina pectoris induced by atherosclerosis.
Fucosyltransferase 1 Mediates Angiogenesis in Rheumatoid Arthritis
Authors: Takeo Isozaki, Mohammad A. Amin, Jeffrey H. Ruth, Phillip L. Campbell, Pei‐Suen Tsou, Christine M. Ha, W. Alex Stinson, Steven E. Domino, Alisa E. Koch
Journal: Arthritis & Rheumatology (2014)

To determine the role of α(1,2)-linked fucosylation of proteins by fucosyltransferase 1 (FUT1) in rheumatoid arthritis (RA) angiogenesis. Analysis of α(1,2)-linked fucosylated proteins in synovial tissue (ST) samples was performed by immunohistologic staining. Expression of α(1,2)-linked fucosylated angiogenic chemokine in synovial fluid (SF) was determined by immunoprecipitation and lectin blotting. To determine the angiogenic role of α(1,2)-linked fucosylated proteins in RA, we performed human dermal microvascular endothelial cell (HMVEC) chemotaxis and Matrigel assays using sham-depleted and α(1,2)-linked fucosylated protein-depleted RA SF samples. To examine the production of proangiogenic chemokines by FUT1 in HMVECs, cells were transfected with FUT1 sense or antisense oligonucleotides, and enzyme-linked immunosorbent assay was performed. We then studied mouse lung endothelial cell (EC) chemotaxis using wild-type and FUT1 gene-deficient mouse lung ECs. RA ST endothelial cells showed high expression of α(1,2)-linked fucosylated proteins compared to normal ST. The expression of α(1,2)-linked fucosylated monocyte chemoattractant protein 1 (MCP-1)/CCL2 was significantly elevated in RA SF compared with osteoarthritis SF. Depletion of α(1,2)-linked fucosylated proteins in RA SF induced less HMVEC migration and tube formation than occurred in sham-depleted RA SF. We found that blocking FUT1 expression in ECs resulted in decreased MCP-1/CCL2 and RANTES/CCL5 production. Finally, we showed that FUT1 regulates EC migration in response to vascular endothelial cell growth factor. Our findings indicate that α(1,2)-linked fucosylation by FUT1 may be an important new target for angiogenic diseases such as RA.
Identification and Testing of a Gene Expression Signature of Invasive Carcinoma Cells within Primary Mammary Tumors
Authors: Weigang Wang, Sumanta Goswami, Kyle Lapidus, Amber L. Wells, Jeffrey B. Wyckoff, Erik Sahai, Robert H. Singer, Jeffrey E. Segall, John S. Condeelis
Journal: Cancer Research (2004)

Abstract We subjected cells collected using an in vivo invasion assay to cDNA microarray analysis to identify the gene expression profile of invasive carcinoma cells in primary mammary tumors. Expression of genes involved in cell division, survival, and cell motility were most dramatically changed in invasive cells indicating a population that is neither dividing nor apoptotic but intensely motile. In particular, the genes coding for the minimum motility machine that regulates β-actin polymerization at the leading edge and, therefore, the motility and chemotaxis of carcinoma cells, were dramatically up-regulated. However, ZBP1, which restricts the localization of β-actin, the substrate for the minimum motility machine, was down-regulated. This pattern of expression implicated ZBP1 as a suppressor of invasion. Reexpression of ZBP1 in metastatic cells with otherwise low levels of ZBP1 reestablished normal patterns of β-actin mRNA targeting and suppressed chemotaxis and invasion in primary tumors. ZBP1 reexpression also inhibited metastasis from tumors. These experiments support the involvement in metastasis of the pathways identified in invasive cells, which are regulated by ZBP1.