tbuckley/cabot-search huggingface dataset:
Release of endothelins and platelet-activating factor by a rat pleural mesothelial cell line
Authors: I Kimura, Y Sakamoto, M Shibasaki, Y Kobayashi, H Matsuo
Journal: European Respiratory Journal (2000)

Thrombin is a multifunctional serine protease. It is generated in inflammatory processes and induces the proliferation and chemotaxis of a variety of cells including mesothelial cells (MTCs). MTCs are epithelial cells derived from the mesoderm, as are the vascular endothelial cells. Since thrombin acts on endothelial cells to produce platelet-activating factor (PAF) and endothelin (ET)-1, it was hypothesized that MTCs also produce PAF and ET via the action of thrombin. Rat pleural MTC (RMTC, 4/4 R.M.-4) monolayers were cultural in tissue culture dishes for various periods. The supernatants were fractionated by means of high-performance liquid chromatography to determine the ET isoforms and PAF species present. Immunoreactive ET was measured using an enzyme-linked immunosorbent assay, and PAF was measured by means of a bioassay using a platelet aggregometer. ET-1, ET-2 and ET-3 were detected in RMTC-conditioned medium, and the predominant isoforms were ET-1 and ET-2. RMTCs mainly released C16:0 PAF into the supernatant. Immunoreactive ET and PAF were released via the action of thrombin. Synthetic PAF significantly induced secretion of ET, but the PAF receptor antagonists, WEB2086 and E6123, failed to modulate thrombin-induced ET release. These results indicate that thrombin acts on pleural rat mesothelial cells to release ET and PAF, which may play a role in the development of pleurisy.
Mesenteric arteritis in systemic lupus erythematosus
Authors: J. C. Philips
Journal: JAMA (1968)

Mesenteric arteriography was performed in a patient who had systemic lupus erythematosus with active intestinal bleeding. The arteriogram demonstrated not only the site of the bleeding, but also diffuse irregularities of the small intestinal arteries. This diffuse irregularity of small vessels correlates well with the pathologic description of diffuse mesenteric arteritis characteristically occurring in this disease entity. Mesenteric arteriography is suggested as the initial diagnostic procedure in patients with collagen disease and who exhibit active, lower-intestinal bleeding.
Kaposi's disease and sarcoidosis
Authors: L Corda, D Benerecetti, M Ungari, F Facchetti, E Radaeli
Journal: European Respiratory Journal (1996)

A human immunodeficiency virus (HIV) antibody-negative 65 year old woman was treated with corticosteroids for 7 yrs because of bilateral uveitis. One year after the beginning of corticosteroid treatment, erythematous skin lesions appeared on the legs. Eight years after the diagnosis of uveitis, gastric and bronchial biopsies revealed noncaseating epithelioid cell granulomas, whilst a cutaneous biopsy showed Kaposi's disease. Sarcoidosis-associated alteration of immune regulation and corticosteroid therapy may have promoted the development of disease.
Molecular basis of ocular abnormalities associated with proximal renal tubular acidosis
Authors: Tomohiko Usui, Masumi Hara, Hiroaki Satoh, Nobuo Moriyama, Humie Kagaya, Shiro Amano, Tetsuro Oshika, Yasuo Ishii, Nobuhiro Ibaraki, Chiaki Hara, Motoei Kunimi, Eisei Noiri, Kazuhisa Tsukamoto, Jun Inatomi, Hayato Kawakami, Hitoshi Endou, Takashi Igarashi, Astuo Goto, Toshiro Fujita, Makoto Araie, George Seki
Journal: Journal of Clinical Investigation (2001)

Proximal renal tubular acidosis associated with ocular abnormalities such as band keratopathy, glaucoma, and cataracts is caused by mutations in the Na+-HCO3– cotransporter (NBC-1). However, the mechanism by which NBC-1 inactivation leads to such ocular abnormalities remains to be elucidated. By immunological analysis of human and rat eyes, we demonstrate that both kidney type (kNBC-1) and pancreatic type (pNBC-1) transporters are present in the corneal endothelium, trabecular meshwork, ciliary epithelium, and lens epithelium. In the human lens epithelial (HLE) cells, RT-PCR detected mRNAs of both kNBC-1 and pNBC-1. Although a Na+-HCO3– cotransport activity has not been detected in mammalian lens epithelia, cell pH (pHi) measurements revealed the presence of Cl–-independent, electrogenic Na+-HCO3– cotransport activity in HLE cells. In addition, up to 80% of amiloride-insensitive pHi recovery from acid load in the presence of HCO3–/CO2 was inhibited by adenovirus-mediated transfer of a specific hammerhead ribozyme against NBC-1, consistent with a major role of NBC-1 in overall HCO3– transport by the lens epithelium. These results indicate that the normal transport activity of NBC-1 is indispensable not only for the maintenance of corneal and lenticular transparency but also for the regulation of aqueous humor outflow.
Targeting antigens to CD180 rapidly induces antigen-specific IgG, affinity maturation, and immunological memory
Authors: Jay W. Chaplin, Craig P. Chappell, Edward A. Clark
Journal: The Journal of Experimental Medicine (2013)

Antigen (Ag) targeting is an efficient way to induce immune responses. Ag is usually coupled to an antibody (Ab) specific for a receptor expressed on dendritic cells (DCs), and then the Ag–anti-receptor is inoculated with an adjuvant. Here we report that targeting Ag to a receptor expressed on both B cells and DCs, the TLR orphan receptor CD180, in the absence of adjuvant rapidly induced IgG responses that were stronger than those induced by Ag in alum. Ag conjugated to anti-CD180 (Ag-αCD180) induced affinity maturation and Ab responses that were partially T cell independent, as Ag-specific IgGs were generated in CD40- and T cell–deficient mice. After preimmunization with Ag-αCD180 and boosting with soluble Ag, both WT and CD40 knockout (KO) mice rapidly produced Ag-specific IgG-forming cells, demonstrating that Ag–anti-CD180 induces immunological memory. The potent adjuvant effect of Ag-αCD180 required Ag to be coupled to anti-CD180 and the responsive B cells to express both CD180 and an Ag-specific B cell receptor. Surprisingly, CD180 Ag targeting also induced IgG Abs in BAFF-R KO mice lacking mature B cells and in mice deficient in interferon signaling. Targeting Ag to CD180 may be useful for therapeutic vaccination and for vaccinating the immune compromised.
NKAML: A Pilot Study to Determine the Safety and Feasibility of Haploidentical Natural Killer Cell Transplantation in Childhood Acute Myeloid Leukemia
Authors: Jeffrey E. Rubnitz, Hiroto Inaba, Raul C. Ribeiro, Stanley Pounds, Barbara Rooney, Teresa Bell, Ching-Hon Pui, Wing Leung
Journal: Journal of Clinical Oncology (2010)

PURPOSE To conduct a pilot study to determine the safety, feasibility, and engraftment of haploidentical natural killer (NK) cell infusions after an immunosuppressive regimen in children with acute myeloid leukemia (AML). PATIENTS AND METHODS Ten patients (0.7 to 21 years old) who had completed chemotherapy and were in first complete remission of AML were enrolled on the Pilot Study of Haploidentical Natural Killer Cell Transplantation for Acute Myeloid Leukemia (NKAML) study. They received cyclophosphamide (60 mg/kg on day -7) and fludarabine (25 mg/m(2)/d on days -6 through -2), followed by killer immunoglobulin-like receptor-human leukocyte antigen (KIR-HLA) mismatched NK cells (median, 29 x 10(6)/kg NK cells) and six doses of interleukin-2 (1 million U/m(2)). NK cell chimerism, phenotyping, and functional assays were performed on days 2, 7, 14, 21, and 28 after transplantation. Results All patients had transient engraftment for a median of 10 days (range, 2 to 189 days) and a significant expansion of KIR-mismatched NK cells (median, 5,800/mL of blood on day 14). Nonhematologic toxicity was limited, with no graft-versus-host disease. Median length of hospitalization was 2 days. With a median follow-up time of 964 days (range, 569 to 1,162 days), all patients remain in remission. The 2-year event-free survival estimate was 100% (95% CI, 63.1% to 100%). CONCLUSION Low-dose immunosuppression followed by donor-recipient inhibitory KIR-HLA mismatched NK cells is well tolerated by patients and results in successful engraftment. We propose to further investigate the efficacy of KIR-mismatched NK cells in a phase II trial as consolidation therapy to decrease relapse without increasing mortality in children with AML.
The Obama Administration's Options for Health Care Cost Control: Hope Versus Reality
Authors: Theodore Marmor
Journal: Annals of Internal Medicine (2009)

Controlling the costs of medical care has long been an elusive goal in U.S. health policy. This article examines the options for health care cost control under the Obama administration. The authors argue that the administration's approach to health reform offers some potential for cost control but also embraces many strategies that are not likely to be successful. Lessons the United States can learn from other countries' experiences in constraining medical care spending are then explored.
Gastric secretory and plasma hormonal responses to sham-feeding of varying duration in patients with duodenal ulcer.
Authors: S J Konturek, J Swierczek, N Kwiecien, W Obtutowicz, M Dobrzanska, B Kopp, J Oleksy
Journal: Gut (1981)

Gastric acid and serum gastrin, pancreatic polypeptide, and insulin responses to cephalic vagal stimulation were studied in eight patients with duodenal ulcer using modified sham-feeding for periods varying from four to 30 minutes. In addition, the maximal acid response to sham-feeding was compared with that induced by pentagastrin in 10 healthy subjects and 14 patients with duodenal ulcer. It was found that the gastric acid response to modified sham-feeding reached the maximal value after 15 minutes of sham-feeding and amounted to about 68% of the pentagastrin maximum. The serum pancreatic polypeptide response was also increased after modified sham-feeding and depended on the duration of this procedure, whereas gastrin and insulin responses were not significantly affected by modified sham-feeding. When the peak acid output induced by modified sham-feeding was normalised as percentage of the peak response to pentagastrin, it was similar in healthy subjects and in patients with duodenal ulcer; this indicates that the increased peak acid response to modified sham-feeding observed in patients with duodenal ulcer corresponded with their greater parietal cell mass rather than with increased vagal tone.
Increased Platelet Inhibition After Switching From Maintenance Clopidogrel to Prasugrel in Patients With Acute Coronary Syndromes
Authors: Dominick J. Angiolillo, Jorge F. Saucedo, Roger DeRaad, Andrew L. Frelinger, Paul A. Gurbel, Timothy M. Costigan, Joseph A. Jakubowski, Clement K. Ojeh, Mark B. Effron
Journal: Journal of the American College of Cardiology (2010)
?-Arginine administration prevents reperfusion-induced cardiomyocyte hypercontracture and reduces infarct size in the pig
Authors: F Padilla
Journal: Cardiovascular Research (2000)

Objective: Stimulation of cGMP synthesis protects cardiomyocytes against reoxygenation-induced hypercontracture. The purpose of this study was to determine whether l-arginine supplementation has a protective effect against reperfusion-induced hypercontracture and necrosis in the intact animal. Methods: Twenty-four Large-White pigs were randomized to receive either 100 mg/kg of l-arginine IV or vehicle 10 min before 48 min of coronary occlusion and 2 h of reperfusion. Hemodynamic variables, coronary blood flow and myocardial segment length changes (piezoelectric crystals) were monitored. Postmortem studies included quantification of myocardium at risk (in vivo fluorescein), infarct size (triphenyltetrazolium reaction), myocardial myeloperoxidase activity and histological analysis. Systemic, coronary vein, and myocardial cGMP concentration were measured in additional animals. Results: Administration of l-arginine had no significant effect in hemodynamics or coronary blood flow. During reperfusion, myocardial cGMP content was reduced in the LAD as compared to control myocardium (P=0.02). l-Arginine increased myocardial cGMP content and caused a transient increase in plasma cGMP concentration during the initial minutes of reperfusion (P=0.02). The reduction in end-diastolic segment length induced by reperfusion, reflecting hypercontracture, was less pronounced in the l-arginine group (P=0.02). Infarct size was smaller in pigs receiving l-arginine (47.9±7.2% of the area at risk) than in controls (62.9±4.9%, P=0.047). There were no differences between groups in leukocyte accumulation in reperfused myocardium (P=0.80). Conclusion:l-Arginine supplementation reduces myocardial necrosis secondary to in situ ischemia–reperfusion by a direct protective effect against myocyte hypercontracture.
Risk of Recurrence and Chemotherapy Benefit for Patients With Node-Negative, Estrogen Receptor–Positive Breast Cancer: Recurrence Score Alone and Integrated With Pathologic and Clinical Factors
Authors: Gong Tang, Jack Cuzick, Joseph P. Costantino, Mitch Dowsett, John F. Forbes, Michael Crager, Eleftherios P. Mamounas, Steven Shak, Norman Wolmark
Journal: Journal of Clinical Oncology (2011)

The 21-gene breast cancer assay recurrence score (RS) is widely used for assessing recurrence risk and predicting chemotherapy benefit in patients with estrogen receptor (ER) -positive breast cancer. Pathologic and clinical factors such as tumor size, grade, and patient age also provide independent prognostic utility. We developed a formal integration of these measures and evaluated its prognostic and predictive value.
Interferon-γ and atherosclerosis: Pro- or anti-atherogenic?
Authors: E HARVEY, D RAMJI
Journal: Cardiovascular Research (2005)

Atherosclerosis is considered to be a form of chronic inflammation governed by a complex network of inter- and intra-cellular signaling pathways. The pleiotropic cytokine interferon-gamma (IFN-gamma) is a key pro-inflammatory mediator that is expressed at high levels in atherosclerotic lesions. IFN-gamma regulates the function and properties of all the cell types in the vessel wall. The precise role of IFN-gamma in atherogenesis is complex, with both pro- and anti-atherogenic actions being identified. This review will discuss these actions of the cytokine along with recent findings that have emerged from mouse models of atherosclerosis that are deficient in IFN-gamma signaling.
Immunobiology of Myasthenia Gravis, Experimental Autoimmune Myasthenia Gravis, and Lambert-Eaton Syndrome
Authors: Jon Lindstrom
Journal: Annual Review of Immunology (1985)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Identification of a Subpopulation of Macrophages in Mammary Tumor–Bearing Mice That Are Neither M1 nor M2 and Are Less Differentiated
Authors: Marta Torroella-Kouri, Risset Silvera, Dayron Rodriguez, Raul Caso, Alwi Shatry, Shannon Opiela, Dan Ilkovitch, Reto A. Schwendener, Vijaya Iragavarapu-Charyulu, Yoslayma Cardentey, Natasa Strbo, Diana M. Lopez
Journal: Cancer Research (2009)

Systemic and local immune deficiency is associated with cancer, and the role of M2 tumor-associated macrophages in this phenomenon is well recognized. However, the immune status of macrophages from peripheral compartments in tumor hosts is unclear. Peritoneal macrophages (PEM) are derived from circulating monocytes and recruited to the peritoneal cavity where they differentiate into macrophages. We have previously shown that PEMs from mice bearing D1-DMBA-3 mammary tumors (T-PEM) are deficient in inflammatory functions and that this impairment is associated with diminished expression of transcription factors nuclear factor kappaB and CAAT/enhancer-binding protein. We now provide evidence that T-PEMs display neither M1 nor M2 phenotypes, yet exhibit deficiencies in the expression of several inflammatory cytokines and various proinflammatory signaling pathways. Moreover, due to nuclear factor kappaB down-regulation, increased apoptosis was observed in T-PEMs. We report for the first time that macrophage depletion is associated with increased macrophage progenitors in bone marrow. Furthermore, T-PEMs have a lower expression of macrophage differentiation markers F4/80, CD68, CD115, and CD11b, whereas Gr-1 is up-regulated. Our results suggest that T-PEMs are less differentiated and represent a newly derived population from blood monocytes. Lastly, we show that transforming growth factor-beta and prostaglandin E(2), two immunosuppressive tumor-derived factors, may be involved in this phenomenon.
Generalised anxiety disorder
Authors: Christopher Gale, Oliver Davidson
Journal: BMJ (2007)

Generalised anxiety disorder is a syndrome of ongoing anxiety and worry about many events or thoughts that the patient generally recognises as excessive and inappropriate. However, the nature of "generalised worry" has been hard to describe in a categorical manner. The criteria required for making a diagnosis are evolving: these criteria clearly increase or decrease markedly the threshold for diagnosis.1 #### SUMMARY POINTS About 1%-5% of the general population report having generalised anxiety disorder. Many of these people also have other disorders, and those with generalised anxiety disorder report a considerable level of disability. Long term follow-up studies suggest that generalised anxiety disorder is a condition that worsens the prognosis for any other condition, and that people who have only generalised anxiety disorder are likely to develop further conditions. The availability of and evidence for efficacious treatments has increased in the past five years. We used the Clinical Evidence database2 then searched for community surveys, randomised controlled trials, and systematic reviews—using the term "generalised anxiety disorder"—in Medline, Embase, and the Cochrane Library up to June 2006. Most of the recent literature uses DSM-IV criteria for generalised anxiety disorder; the ICD-10 criteria place greater weight on somatic symptoms and explicitly limit comorbidity (box). #### Current diagnostic criteria for generalised anxiety disorder ##### Diagnostic and statistical manual of mental disorders (DSM-IV-TR)
Detection of upper gastrointestinal cancer in patients taking antisecretory therapy prior to gastroscopy
Authors: M G Bramble
Journal: Gut (2000)

The incidence of early gastric cancer has not increased despite better access to endoscopic facilities for general practitioners. Many patients receive a course of symptomatic treatment while waiting for gastroscopy.To ascertain the effect of antisecretory therapy on the diagnostic process and findings for patients with upper gastrointestinal cancer.A consecutive case study survey of the primary care records of 133 patients who had died of upper gastrointestinal cancer during 1995-97 in the South Tees health district in the north-east of England (population 300 000).From the 133 patients identified, 116 had died from adenocarcinoma of the oesophagus (31) or stomach (85). Failure to reach the diagnosis of cancer at the index gastroscopy was associated with prior acid suppression therapy. Only one of 54 patients on no treatment or antacids alone was erroneously diagnosed as suffering from benign disease, whereas 22 of 62 patients treated with acid suppression were diagnosed as suffering from benign disease but at varying times later turned out to have adenocarcinoma. Twenty of 45 patients taking a proton pump inhibitor had a delayed diagnosis compared with two of 17 taking an H(2) receptor antagonist. The commonest lesion seen at index gastroscopy in those in whom the diagnosis was initially missed was gastric ulcer. Healing occurred in six patients taking a proton pump inhibitor, despite their later diagnosis of malignancy.The treatment of dyspeptic symptoms with acid suppression prior to gastroscopy masks and delays the detection of gastric and oesophageal adenocarcinoma on endoscopy in one third of patients.
Furosemide Stress Test and Biomarkers for the Prediction of AKI Severity
Authors: Jay L. Koyner, Danielle L. Davison, Ermira Brasha-Mitchell, Divya M. Chalikonda, John M. Arthur, Andrew D. Shaw, James A. Tumlin, Sharon A. Trevino, Michael R. Bennett, Paul L. Kimmel, Michael G. Seneff, Lakhmir S. Chawla
Journal: Journal of the American Society of Nephrology (2015)

Clinicians have access to limited tools that predict which patients with early AKI will progress to more severe stages. In early AKI, urine output after a furosemide stress test (FST), which involves intravenous administration of furosemide (1.0 or 1.5 mg/kg), can predict the development of stage 3 AKI. We measured several AKI biomarkers in our previously published cohort of 77 patients with early AKI who received an FST and evaluated the ability of FST urine output and biomarkers to predict the development of stage 3 AKI (n=25 [32.5%]), receipt of RRT (n=11 [14.2%]), or inpatient mortality (n=16 [20.7%]). With an area under the curve (AUC)±SEM of 0.87±0.09 (P<0.0001), 2-hour urine output after FST was significantly better than each urinary biomarker tested in predicting progression to stage 3 (P<0.05). FST urine output was the only biomarker to significantly predict RRT (0.86±0.08; P=0.001). Regardless of the end point, combining FST urine output with individual biomarkers using logistic regression did not significantly improve risk stratification (ΔAUC, P>0.10 for all). When FST urine output was assessed in patients with increased biomarker levels, the AUC for progression to stage 3 improved to 0.90±0.06 and the AUC for receipt of RRT improved to 0.91±0.08. Overall, in the setting of early AKI, FST urine output outperformed biochemical biomarkers for prediction of progressive AKI, need for RRT, and inpatient mortality. Using a FST in patients with increased biomarker levels improves risk stratification, although further research is needed.
Significance of anti-inflammatory effects of PPAR agonists?
Authors: G Rogler
Journal: Gut (2005)

Peroxisome proliferator activated receptor γ expression in mucosal epithelial cells seems to be crucial for its anti-inflammatory effects with respect to experimental colitis, and for maintaining homeostasis of the mucosal barrier, at least in animal models

The peroxisome proliferator activated receptor γ (PPARγ) is one of three members of the PPAR family (PPARα and PPARδ), which itself is a part of the nuclear hormone receptor superfamily.1–5 Nuclear hormone receptors are transcription factors that are activated by the binding of small lipophilic ligands.6,7,8,9,10,11 They induce or repress transcription of a large number of different genes thereby influencing cellular functions.

PPARγ was initially identified for its role in adipocyte differentiation and regulation of genes involved in lipid and glucose metabolism.12–15 However, activation of PPARγ also can antagonise nuclear factor κB (NFκB) action in macrophages resulting in downregulation of proinflammatory cytokines.10,16–22 Implicated in these anti-inflammatory properties, PPARγ is not only expressed in adipocytes but also in a number of other cells types, such as macrophages,9 lymphocytes, hepatocytes, and skeletal muscle. Very high expression levels are found in the colonic epithelium.23

Interestingly, the proinflammatory genes that are repressed by PPARγ overlap but are not identical to the genes that are downregulated by the glucocorticoid receptor (GR), another member of the nuclear hormone receptor superfamily which intracellularly mediates the effects of endogenous cortisol and therapeutically administrated glucocorticoids.24 PPARγ mediated effects in the experimental setting of toll-like receptor stimulation were independent of NFκB and interferon regulatory factor, in contrast with GR action.24 This indicates that glucocorticoids and ligands of PPARγ could have additive therapeutic effects.

The eicosanoids 13-hydroxyoctadecadienoic acid and 15-hydroxyeicosatetraenoic acid as well as 15deoxy-Δ12,14,-prostaglandin J2 have …