tbuckley/cabot-search huggingface dataset:
Alveolar JE/MCP-1 and Endotoxin Synergize to Provoke Lung Cytokine Upregulation, Sequential Neutrophil and Monocyte Influx, and Vascular Leakage in Mice
Authors: ULRICH MAUS, JULIA HUWE, REGINA MAUS, WERNER SEEGER, JÜRGEN LOHMEYER
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

The C-C chemokine monocyte chemotactic protein 1 (JE/MCP-1) is a key cytokine for lung monocyte recruitment, and may be detected in high levels in the alveolar space in lung injury. We hypothesized that alveolar JE/MCP-1 might synergize with endotoxin in this compartment to elicit lung inflammatory events. Intratracheal instillation of JE/MCP-1 into BALB/c mice did not provoke increased bronchoalveolar lavage tumor necrosis factor α (TNF- α ), interleukin 6 (IL-6), and macrophage inflammatory protein 2 (MIP-2) levels, but elicited monocyte recruitment into this compartment. Intratracheal Escherichia coli endotoxin provoked elevated lavage TNF- α , IL-6, and MIP-2 levels, peaking after 6 h in parallel with increased alveolar neutrophil numbers, in the absence of vascular leakage. Mice receiving both endotoxin and JE/ MCP-1 showed drastically increased lavage TNF- α , IL-6, and MIP-2 levels, 22-fold higher lavage neutrophil numbers, and lung vascular leakage. Moreover, an 8-fold increased alveolar accumulation of monocytes, peaking at 48 h together with expansion of the resident alveolar macrophage pool, was noted. Intraperitoneal instead of alveolar deposition of MCP-1 or endotoxin failed to reproduce the synergistic response, and the same was true for employment of RANTES instead of MCP-1. Blockade of neutrophil recruitment by anti-CD18 did not affect the intra-alveolar cytokine response to MCP-1 plus endotoxin. Together, JE/MCP-1 and endotoxin, when coappearing in the alveolar compartment at low dosage, elicit an early phase of lung inflammatory injury with increased cytokine synthesis and neutrophil recruitment, and a late phase of enhanced monocyte traffic and expansion of the alveolar macrophage pool.Keywords: lung; cytokine; alveolar monocyte; inflammation
The online Cough Clinic: developing guideline-based diagnosis and advice
Authors: P. W. Dettmar, V. Strugala, H. Fathi, H. J. Dettmar, C. Wright, A. H. Morice
Journal: European Respiratory Journal (2009)

The aim of the present study was make chronic cough guidelines more practical and user friendly by developing an internet-based interactive diagnostic questionnaire for chronic cough. A prospective cohort study of chronic cough sufferers was conducted in the UK, following European Respiratory Society guidelines for the diagnosis and management of chronic cough. Depending on the response to 16 specific questions, the medical condition responsible for the patient's chronic cough was ascertained according to a predetermined diagnostic algorithm designed to differentiate the three common causes of chronic cough. Appropriate advice and treatment recommendations were then provided. 8,546 adults with chronic cough completed the Cough Clinic diagnostic questionnaire. 46.1% were suggested to have reflux, 38.7% asthma and 15.2% rhinitis. Participants found the website easy to use (94%), the advice helpful (73%) and that it helped them to communicate with their general practitioner better (60%), and 62% reported taking the recommended treatment. The Cough Clinic, an internet-based diagnostic site for chronic cough, had a large uptake by chronic cough sufferers in the UK. Almost half were diagnosed as having reflux as the probable cause of their chronic cough. Internet diagnosis by expert algorithm provides a novel mechanism for patients to access guideline-recommended therapies and enhances dialogue between patients and physicians.
Endoscopic Closure of Transmural Bladder Wall Perforations
Authors: Estevao Lima, Carla Rolanda, Luís Osório, José M. Pêgo, David Silva, Tiago Henriques-Coelho, José L. Carvalho, Maria Bergström, Per-Ola Park, Charles A. Mosse, Paul Swain, Jorge Correia-Pinto
Journal: European Urology (2008)
Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study
Authors: Karen L Kotloff, James P Nataro, William C Blackwelder, Dilruba Nasrin, Tamer H Farag, Sandra Panchalingam, Yukun Wu, Samba O Sow, Dipika Sur, Robert F Breiman, Abu SG Faruque, Anita KM Zaidi, Debasish Saha, Pedro L Alonso, Boubou Tamboura, Doh Sanogo, Uma Onwuchekwa, Byomkesh Manna, Thandavarayan Ramamurthy, Suman Kanungo, John B Ochieng, Richard Omore, Joseph O Oundo, Anowar Hossain, Sumon K Das, Shahnawaz Ahmed, Shahida Qureshi, Farheen Quadri, Richard A Adegbola, Martin Antonio, M Jahangir Hossain, Adebayo Akinsola, Inacio Mandomando, Tacilta Nhampossa, Sozinho Acácio, Kousick Biswas, Ciara E O'Reilly, Eric D Mintz, Lynette Y Berkeley, Khitam Muhsen, Halvor Sommerfelt, Roy M Robins-Browne, Myron M Levine
Journal: The Lancet (2013)
Remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) as recurrence of aborted PMR
Authors: M A CIMMINO
Journal: Annals of the Rheumatic Diseases (2001)

A comparison of clinical and laboratory findings in patients with RS3PE alone, PMR alone, and RS3PE associated with PMR has been recently published by Cantini et al .1 Their results suggest that the three conditions might represent a continuum, with PMR, a more severe condition, at one end and, RS3PE alone, at the other. PMR has a longer duration, is more commonly associated with systemic symptoms, requires higher doses of steroids for a longer time, and shows more relapses and recurrences. Although Cantini et al emphasised the similarities between PMR and RS3PE, they concluded that RS3PE alone is a separate entity. Other studies by the same group of authors have shown that RS3PE may be a feature of different diseases, such as spondyloarthropathies, psoriatic arthritis, rheumatoid arthritis (RA), acute sarcoidosis, and neoplasms.2 Whether RS3PE is a distinct syndrome or a clinical …
The Future of Ultrasonography
Authors: Scott L. Bernstein
Journal: JAMA (1991)

Future advances in ultrasonography will undoubtedly occur in three major areas: diagnostic capability, instrumentation, and clinical applications. In the area of diagnostic capability, spatial and contrast resolution offer excellent opportunities for improvement. Continued research into tissue characterization is worthwhile, even though efforts to date have been more frustrating than fulfilling. Blood flow studies and new contrast agents are among the more promising areas for future development. New techniques of signal detection, analysis, and display in Doppler imaging may overcome some present limitations, including those in color flow imaging. (<i>JAMA</i>. 1991;266:406-409)
Kinetics of HbA1c, Glycated Albumin, and Fructosamine and Analysis of Their Weight Functions Against Preceding Plasma Glucose Level
Authors: Yasuhiro Tahara, Kenji Shima
Journal: Diabetes Care (1995)

To examine the kinetics of HbA1c, glycated albumin (GA), and fructosamine (FA) levels in response to plasma glucose change and their relationship with the preceding plasma glucose level.The time courses of HbA1c, GA, and FA after acute glycemic normalization were observed in nine patients with newly diagnosed non-insulin-dependent diabetes mellitus and compared with theoretical ones. Their weight functions against preceding plasma glucose level were analyzed assuming a stepwise plasma glucose change and compared with the theoretical prediction.The fasting plasma glucose level was acutely normalized after admission with a half-time of 6.3 +/- 2.4 days (mean +/- SD). The HbA1c level decreased linearly during the initial 2 months with a half-time of 34.6 +/- 10.1 days, followed by a gradual decrease thereafter. GA and FA levels decreased very rapidly during the initial 2-3 weeks with half-times of 17.1 +/- 2.8 and 12.2 +/- 4.8 days, respectively, followed by a gradual decrease thereafter. The time courses of HbA1c, GA, and FA agreed well with theoretically estimated decay curves. Experimental values of weight functions against the preceding plasma glucose level agreed well with the theoretical prediction. The weight functions for glycated proteins had maximum values on the days just before the measurement of glycated proteins and gradually decreased with an increasing time interval. The lengths of the periods over which the weight functions for HbA1c, GA, and FA extend back were estimated to be roughly 100, 40, and 30 days, respectively.The levels of HbA1c, GA, and FA do not reflect the simple mean but reflect the weighted mean of the preceding plasma glucose level over a considerably longer period than was previously speculated.
Increased 5-lipoxygenase activity in massive hepatic cell necrosis in the rat correlates with neutrophil infiltration
Authors: Norifumi Kawada, Natsuo Ueda, Yasuhiro Mizoguchi, Kenzo Kobayashi, Takeyuki Monna, Seiji Morisawa, Kazunori Ishimura, Toshiko Suzuki, Shozo Yamamoto
Journal: Hepatology (1992)

Rats were treated with heat-killed Propionibacterium acnes and subsequent injection of a small amount of lipopolysaccharide after 7 days. After 24 hr most of the rats died of massive liver cell necrosis. Nonparenchymal liver cells were isolated from this liver injury model and incubated with arachidonic acid. Reverse-phase high-pressure liquid chromatography detected the 5-lipoxygenase metabolites (leukotriene B4 and 5-hydroxy-arachidonic acid), whereas these compounds were produced in negligible amounts when the rats were treated with P. acnes only. Immunohistochemical studies with 5-lipoxygenase antiserum revealed that the injured livers contained a large number of positively stained round cells with segmented nuclei, which were rarely found in the livers treated with P. acnes only. These positively stained cells were histologically identified as neutrophils. The results suggested that the increased 5-lipoxygenase activity in the injured rat liver is attributable to the infiltrating neutrophils rather than to nonparenchymal hepatic cells.
Interleukin-17 and CD40-Ligand Synergistically Enhance Cytokine and Chemokine Production by Renal Epithelial Cells
Authors: ANDREA M. WOLTMAN, SIMONE DE HAIJ, JOKE G. BOONSTRA, SAM J.P. GOBIN, MOHAMED R. DAHA, CEES VAN KOOTEN
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Renal allograft rejection is characterized by an influx of inflammatory cells. Interaction between infiltrating T cells and resident parenchymal cells might play an important role in the ongoing inflammatory response. The present study demonstrates that CD40L, a product of activated T cells, is locally expressed in kidneys undergoing rejection. Furthermore, during rejection, CD40 expression not only is present on most graft infiltrating cells but also is increased on resident tubular epithelial cells (TEC). To obtain more detailed insight in the consequences of T cell/TEC interaction, we analyzed the production of chemokines, including interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1) and regulated upon activation, normal T cell expressed and secreted (RANTES), and the production of IL-6 by cultured human primary TEC in response to activation with CD40L in vitro . In addition, we studied the interaction with IL-17, a T-cell—specific cytokine previously demonstrated to be present during renal allograft rejection. The results, obtained by enzyme-linked immunosorbent assay, indicate that simultaneous activation of TEC with IL-17 and CD40L synergistically enhances production of IL-6 (2.1-fold higher than sum of single stimulations) and the chemokines IL-8 (15-fold) and RANTES (5.8-fold) as demonstrated by statistical analysis ( P &lt; 0.05), whereas effects on MCP-1 (1.4-fold) are additive. Part of the synergy can be explained by increased CD40 expression on TEC upon IL-17 stimulation. The synergy is not unique for TEC, because similar responses were found with human synoviocytes and a foreskin fibroblast cell line (FS4). Stimulation of TEC with CD40L results in activation of NF-κB and induction of cytokine production by IL-17 and CD40L is prevented by addition of the NF-κB inhibitor pyrrolidine dithiocarbamate. These data suggest an important role for T cells in renal allograft rejection by acting on parenchymal cells via both soluble mediators and direct cellular contact.
Angiotensin-converting enzyme inhibition reduces monocyte chemoattractant protein-1 and tissue factor levels in patients with myocardial infarction
Authors: Hirofumi Soejima, Hisao Ogawa, Hirofumi Yasue, Koichi Kaikita, Keiji Takazoe, Koichi Nishiyama, Kenji Misumi, Shinzo Miyamoto, Michihiro Yoshimura, Kiyotaka Kugiyama, Shin Nakamura, Ichiro Tsuji
Journal: Journal of the American College of Cardiology (1999)
Increased Toll-Like Receptor Activity in Patients With Metabolic Syndrome
Authors: Ishwarlal Jialal, Beverley A. Huet, Harmeet Kaur, Alexander Chien, Sridevi Devaraj
Journal: Diabetes Care (2012)

The metabolic syndrome (MetS) is highly prevalent and confers an increased risk for diabetes and cardiovascular disease (CVD). While MetS is a proinflammatory state, there is a paucity of data on cellular inflammation in MetS. Toll-like receptors (TLRs) are classical pattern recognition receptors of the innate immune response.The aim of this study was to examine monocyte TLR2 and TLR4 in MetS patients without diabetes or CVD and control subjects since both of the receptors have been implicated in atherosclerosis and insulin resistance. Fasting blood was obtained for TLR expression and activity.Circulating levels of high-sensitivity C-reactive protein, interleukin (IL)-1β, IL-6, IL-8, and soluble tumor necrosis factor receptor 1 (sTNFR1) were significantly increased in MetS versus control subjects following adjustment for waist circumference. There was a significant increase in both TLR2 and TLR4 surface expression and mRNA on monocytes after adjustment for waist circumference. In addition to increased nuclear factor-κB nuclear binding, there was significantly increased release of IL-1β, IL-6, and IL-8 in MetS versus control subjects following priming of the monocytes with lipopolysaccharides. While both plasma free fatty acids and endotoxin were increased in MetS, they correlated significantly with TLR4 only.In conclusion, we make the novel observation that both TLR2 and TLR4 expression and activity are increased in the monocytes of patients with MetS and could contribute to increased risk for diabetes and CVD.
Interleukin-1 receptor antagonist ameliorates experimental anti-glomerular basement membrane antibody-associated glomerulonephritis.
Authors: W W Tang, L Feng, J L Vannice, C B Wilson
Journal: Journal of Clinical Investigation (1994)

The contribution of IL-1 to leukocyte infiltration in anti-glomerular basement membrane (GBM) antibody (Ab) glomerulonephritis (GN) was examined by the administration of a specific IL-1 receptor antagonist (IL-1ra). Lewis rats received anti-GBM Ab or normal rabbit serum and were treated with either 0.9% saline or 6 mg IL-1ra over a 24-h time period. Plasma IL-1ra concentration was 2,659 +/- 51 ng/ml 4 h after anti-GBM Ab and IL-1ra administration. PMN and monocyte/macrophage infiltration declined 39% (9.8 +/- 1.9 to 6.0 +/- 1.5 PMN/glomerulus, P < 0.001) and 29% (4.9 +/- 0.8 to 3.5 +/- 0.8 ED-1 cells/glomerulus, P = 0.002) with IL-1ra treatment at 4 h, respectively. Similarly, the number of glomerular cells staining for lymphocyte function-associated molecule-1 beta (CD18) declined 39% from 16.7 +/- 1.9 to 10.7 +/- 1.6 cells/glomerulus at 4 h (P = 0.0001). This was associated with a decrease in glomerular intracellular adhesion molecule-1 expression. The mean glomerular intracellular adhesion molecule-1 score in anti-GBM Ab GN rats treated with IL-1ra was less than that of rats administered anti-GBM Ab and 0.9% saline at 4 (2.0 +/- 0.2 vs 2.5 +/- 0.2, P < 0.05) and 24 (2.5 +/- 0.1 vs 3.1 +/- 0.2, P = 0.0001) h. These immunopathologic changes correlated with a 50% reduction in proteinuria from 147 +/- 34 to 75 +/- 25 mg/d (P < 0.002). Treatment with IL-1ra did not affect the steady state mRNA expression of either IL-1 beta or TNF alpha. An increase in the IL-1ra dose to 30 mg given within the initial 4 h provided no additional benefit. The decline in PMN and monocyte/macrophage infiltration of the glomerulus at 4 h was similar to that found in the initial study. Furthermore, the protective benefit of IL-1ra was abrogated by doubling the dose of the anti-GBM Ab GN, despite administering high dose IL-1ra (30 mg). In these studies, detectable IL-1ra was found in the serum of untreated anti-GBM Ab GN controls. These data suggest a positive yet limited role for IL-1ra in the therapeutic intervention of anti-GBM Ab GN.
The thickness of the epidermis
Authors: JUDI T. WHITTON, J.D. EVERALL
Journal: British Journal of Dermatology (1973)

Epidermal thickness has been accurately measured on 214 samples of skin from 188 volunteers. Variations with the individual, body site, sex and age are described and discussed. An original technique of measurement has been developed which has several advantages over conventional methods. In particular, quick straight‐forward measurements are possible on volunteer skin rather than post mortem material, and the method eliminates errors arising from the skin's elasticity. These improvements in accuracy have confirmed that much information in the literature on epidermal thickness, is misleading as the results are based on inaccurate techniques of measurement.
Effects of a Potent and Selective PPAR-α Agonist in Patients With Atherogenic Dyslipidemia or Hypercholesterolemia
Authors: Steven E. Nissen, Stephen J. Nicholls, Kathy Wolski, Daniel C. Howey, Ellen McErlean, Ming-Dauh Wang, Elisa V. Gomez, John M. Russo
Journal: JAMA (2007)

Fibrates are weak agonists of peroxisome proliferator-activated receptor alpha (PPAR-alpha). No trials have reported effects of more potent and selective agents.To examine the safety and efficacy of LY518674, a PPAR-alpha agonist.Two multicenter, randomized, double-blind, placebo-controlled trials: 1 in patients with elevated triglycerides and low HDL-C (atherogenic dyslipidemia), the other in patients with elevated LDL-C (hypercholesterolemia). Between August 2005 and August 2006, the dyslipidemia study randomized 309 patients at US centers; the hypercholesterolemia study, 304 patients.Dyslipidemia study: placebo, fenofibrate (200 mg), or LY518674 (10, 25, 50, or 100 microg) for 12 weeks. Hypercholesterolemia study: placebo or atorvastatin (10 or 40 mg) for 4 weeks, then placebo or LY518674 (10 or 50 microg) for 12 more weeks.Dyslipidemia study: percentage change in levels of HDL-C and triglycerides. Hypercholesterolemia study: percentage change in levels of LDL-C.Dyslipidemia study: LY518674 (25 mug) and fenofibrate increased HDL-C by 5.9 and 5.5 mg/dL (15.8% and 14.4%) (both P< or =.001 vs placebo, P = .79 between treatments). Higher LY518674 doses yielded smaller increases. LY518674 decreased triglycerides by 97.3 to 114.5 mg/dL (34.9% to 41.7%) but was similar to fenofibrate. LY518674 produced a dose-dependent increase in LDL-C, reaching 20.4 mg/dL (19.5%) for the 100-mug dose vs 0.3 mg/dL (2.3%) for fenofibrate (P< or =.01). Fenofibrate and LY518674 (50 microg and 100 microg) increased serum creatinine (P< or =.001 vs placebo), with 38% and 37.3% of patients exceeding the normal range. Fenofibrate, but not LY518674, increased creatine phosphokinase (P = .004 vs placebo). Hypercholesterolemia study: LY518674 (10 mug or 50 microg) decreased LDL-C by 21.4 to 26.0 mg/dL (13.2%-15.8%) and triglycerides approximately 37% for both doses, and increased HDL-C by 6.3 to 6.7 mg/dL (12.5%-15.0%). When added to atorvastatin, LY518674 changed HDL-C by -0.7 to 6.2 mg/dL (-0.6% to 11.9%) and significantly decreased triglycerides but had no additional effect on LDL-C.In patients with dyslipidemia, LY518674 and fenofibrate decreased triglycerides and increased HDL-C but also increased serum creatinine. LY518674, but not fenofibrate, increased LDL-C. In those with hypercholesterolemia, LY518674 reduced triglycerides and increased HDL-C, but did not further reduce LDL-C in combination with atorvastatin. Fenofibrate and LY518674 both raised safety concerns.clinicaltrials.gov Identifiers: NCT00133380 and NCT00116519
Effect of acetylcholine on vascular capacity in the dog.
Authors: E W Supple, W J Powell
Journal: Journal of Clinical Investigation (1981)

Acetylcholine produces venoconstriction of isolated vein strip preparations. However, the effect of acetylcholine on overall vascular capacity is not known. To investigate this effect and to elucidate the mechanisms involved, 38 anesthetized dogs were placed on total cardiopulmonary bypass, splenectomized, and given intraarterial infusions of acetylcholine. Almost all of the effect on vascular volume was found to be in the splanchnic circulation, because in four eviscerated animals there was no significant change in capacity. In the animals in which the mesenteric arteries were cannulated to provide constant inflow, and the hepatic vein was cannulated to measure splanchnic venus outflow, acetylcholine infusion for 5 and 21 min increased splanchnic vascular capacity in all animals by 107 +/- 28 (SEM)ml (p less than 0.01) and 291 +/- 132 ml (p less than 0.05), respectively. This increase in splanchnic vascular volume was associated with a rapid and sustained increase in transhepatic resistance to portal blood flow for the duration of the infusions (p less than 0.01). In the animals in which the portal vein was vented proximal to the liver, no significant volume change occurred in the splanchnic vasculature with acetylcholine infusion. Increasing hepatic venous pressure to elevate portal venous pressure to the same level as that achieved with acetylcholine resulted in a similar increase in splanchnic vascular volume. Atropine, but not adrenergic blockade, blocked the acetylcholine-induced volume retention, indicating that the effect of acetylcholine was direct. Substantial volume retention was also achieved by stimulation of the distal ends of the sectioned cervical vagi. Thus, acetylcholine administration directly increases transhepatic resistance and is associated with a pooling of volume in the splanchnic vasculature that would, in the intact animal, result in a decrease in venous return to the heart.
Quantitative estimation of irbesartan in two different matrices and its application to human and dog bioavailability studies using LC–MS/MS
Authors: Hari Krishan Tiwari, Tausif Monif, Priya Ranjan Prasad Verma, Simrit Reyar, Arshad Hussain Khuroo, Sanjeev Mishra
Journal: Asian Journal of Pharmaceutical Sciences (2013)

A simple, rapid and robust high-throughput assay for the quantitative analysis of irbesartan in plasma from two species using liquid chromatography tandem mass spectrometric method was developed and validated. Solid phase extraction was used and quantification was achieved using a positive electrospray ionization interface under multiple reactions monitoring condition. Complete validation (as per recent regulatory requirements) was done using human plasma. The same method was validated using dog plasma and the validation parameters met respective acceptance criteria. The method has shorter run time of 3 min. This will help in high throughput. The low aliquot volume in the method helped us to take enough sampling time points for better pharmacokinetic profiles. The calibration curve was shown to be linear from 12.1 to 6018.7 ng/ml in human plasma and 12.1 to 5987.2 ng/ml in dog plasma. This method was successfully applied to samples collected during bioavailability studies of irbesartan in humans and dogs.