tbuckley/cabot-search huggingface dataset:
EXPERIMENTAL IMMUNE COMPLEX DISEASE OF THE LUNG
Authors: Jan R. Brentjens, David W. O'Connell, Irene B. Pawlowski, Konrad C. Hsu, Giuseppe A. Andres
Journal: The Journal of Experimental Medicine (1974)

Membranous and/or proliferative pneumonitis, similar in certain features to human interstitial pneumonitis, developed in rabbits making hyperactive antibody response to daily injections of bovine serum albumin (BSA) administered in multiple large doses sufficient to maintain the state of relative antigen-antibody equivalence. The pulmonary lesions were associated with deposition in alveolar capillary walls and interstitium of antigen, host globulin and complement, presumably in immune complexes. In some rabbits chronic interstitial pneumonitis, characterized by thickening of alveolar capillary walls, interstitial fibrosis and deposition of fibrinogen, was observed. The production of immune complex pneumonitis seems to depend on the degree of the antibody response because rabbits developing chronic serum sickness with low doses of BSA, rabbits with acute serum sickness as well as nonresponders showed no pulmonary alterations. This observation is comparable to that described by Dixon in his studies on experimental immune complex glomerulonephritis. It is conceivable that the pulmonary pathology shown here is produced by formation of larger amounts of complexes which may persist longer at critical levels in the circulation than in rabbits immunized with a single daily injection of BSA. In conclusion this study suggests: first, that experimental chronic serum sickness can be used as a model, not only for glomerulonephritis, but also for experimental systemic disease, comparable to human systemic diseases produced by circulating antigen-antibody complexes; and second, that the pathogenesis proposed here offers an alternative to using antilung basement membrane pneumonitis for the experimental approach to the study of human lung immunopathology.
Neutrophil depletion limited to reperfusion reduces myocardial infarct size after 90 minutes of ischemia. Evidence for neutrophil-mediated reperfusion injury.
Authors: M R Litt, R W Jeremy, H F Weisman, J A Winkelstein, L C Becker
Journal: Circulation (1989)

Reperfusion of ischemic myocardium may accelerate necrosis of injured myocytes. To determine the role of neutrophil leukocytes in this process, we examined whether neutrophil depletion during reperfusion could modify infarct size in anesthetized dogs. The proximal circumflex coronary artery was occluded for 90 minutes and then reperfused for 2 hours via an extracorporeal circuit with either whole blood (n = 11) or with blood depleted of neutrophils by leukocyte filters (n = 11). The leukocyte filters caused near-total neutropenia in blood reperfusing the ischemic myocardium (7 +/- 7 neutrophils/microliters compared with 2,551 +/- 317/microliters in controls, mean +/- SEM; p less than 0.001. Infarct size was measured by planimetry of myocardial slices stained with triphenyltetrazolium chloride (TTC), and the accuracy of TTC for identifying necrotic myocardium was verified by electron microscopy. The size of the ischemic risk region was the same in the control (41.6 +/- 1.0%) and neutropenic (41.8 +/- 2.1%) groups. Collateral blood flow to the risk region was the same in control (0.15 +/- 0.03 ml/min/g) and neutropenic (0.13 +/- 0.03 ml/min/g) groups. Among dogs with collateral flow less than 0.2 ml/min/g, infarct size was reduced in the neutropenic group (27.7 +/- 6.7% of risk region, n = 8), compared with control dogs (52.5 +/- 5.7%; n = 7; p = 0.02). Multiple linear regression described the relation between infarct size, risk region size, and collateral flow in the control group, and the same regression relation was used to predict infarct size for the neutropenic group. Mean predicted infarct size in the neutropenic group (n = 11) was 16.8 +/- 3.4% of left ventricle, whereas mean observed infarct size was 9.6 +/- 3.1% (p less than 0.01). The extent of the no-reflow zone (absence of thioflavin-S-fluorescence) was also less in the neutropenic than the control group (2.2 +/- 0.8% vs. 8.1 +/- 2.7% of the risk region, p less than 0.05). Neutropenia limited to the reperfusion period is associated with significant reductions in the extent of the infarct and no-reflow zones after 90 minutes of ischemia. These findings support the hypothesis that reperfusion necrosis occurs after prolonged myocardial ischemia and indicate that neutrophil leukocytes are important mediators of such reperfusion injury.
Intraepithelial and lamina propria lymphocytes show distinct patterns of apoptosis whereas both populations are active in Fas based cytotoxicity in coeliac disease
Authors: A Di Sabatino, R Ciccocioppo, S D'Alò, R Parroni, D Millimaggi, M G Cifone, G R Corazza
Journal: Gut (2001)

Lamina propria (LPLs) and intraepithelial (IELs) lymphocytes are markedly increased in coeliac mucosa, and are thought to play a crucial role in the generation of villous atrophy in coeliac disease (CD). However, the mechanisms by which they mediate the killing of enterocytes in this condition are still poorly characterised.We investigated Fas mediated cytotoxicity and apoptosis of both LPLs and IELs, isolated from 10 untreated coeliac patients, 10 coeliac patients on a gluten free diet, and 10 biopsied controls.Fas and Fas ligand expression were assessed by flow cytometry and immunocytochemistry. Lymphocyte cytotoxicity against Fas expressing Jurkat cells was determined by the Jam test. The effect of the antagonist ZB4 anti-Fas antibody on apoptotic activity exerted by coeliac lymphocytes against enterocytes was analysed. Lymphocyte apoptosis was assessed by oligonucleosome ELISA.LPLs and IELs showed increased apoptotic activity and higher levels of Fas ligand expression in untreated CD compared with treated CD patients and controls. Enterocyte apoptosis observed after coculturing coeliac lymphocytes and enterocytes in the presence of ZB4 antibody was reduced. In active CD, LPLs manifested increased apoptosis whereas IELs showed decreased apoptosis.Our results support the involvement of the Fas/Fas ligand system in CD associated enterocyte apoptosis. Increased LPL apoptosis is likely to downregulate mucosal inflammation whereas decreased IEL apoptosis could be responsible for autoimmune and malignant complications of CD.
HLA class I associations of ankylosing spondylitis in the white population in the United Kingdom.
Authors: M A Brown, K D Pile, L G Kennedy, A Calin, C Darke, J Bell, B P Wordsworth, F Cornelis
Journal: Annals of the Rheumatic Diseases (1996)

OBJECTIVE: To investigate the HLA class I associations of ankylosing spondylitis (AS) in the white population, with particular reference to HLA-B27 subtypes. METHODS: HLA-B27 and -B60 typing was performed in 284 white patients with AS. Allele frequencies of HLA-B27 and HLA-B60 from 5926 white bone marrow donors were used for comparison. HLA-B27 subtyping was performed by single strand conformation polymorphism (SSCP) in all HLA-B27 positive AS patients, and 154 HLA-B27 positive ethnically matched blood donors. RESULTS: The strong association of HLA-B27 and AS was confirmed (odds ratio (OR) 171, 95% confidence interval (CI) 135 to 218; p &lt; 10(-99)). The association of HLA-B60 with AS was confirmed in HLA-B27 positive cases (OR 3.6, 95% CI 2.1 to 6.3; p &lt; 5 x 10(-5)), and a similar association was demonstrated in HLA-B27 negative AS (OR 3.5, 95% CI 1.1 to 11.4; p &lt; 0.05). No significant difference was observed in the frequencies of HLA-B27 allelic subtypes in patients and controls (HLA-B*2702, three of 172 patients v five of 154 controls; HLA-B*2705, 169 of 172 patients v 147 of 154 controls; HLA-B*2708, none of 172 patients v two of 154 controls), and no novel HLA-B27 alleles were detected. CONCLUSION: HLA-B27 and -B60 are associated with susceptibility to AS, but differences in HLA-B27 subtype do not affect susceptibility to AS in this white population.
Telaprevir for Retreatment of HCV Infection
Authors: Stefan Zeuzem, Pietro Andreone, Stanislas Pol, Eric Lawitz, Moises Diago, Stuart Roberts, Roberto Focaccia, Zobair Younossi, Graham R. Foster, Andrzej Horban, Peter Ferenci, Frederik Nevens, Beat Müllhaupt, Paul Pockros, Ruben Terg, Daniel Shouval, Bart van Hoek, Ola Weiland, Rolf Van Heeswijk, Sandra De Meyer, Don Luo, Griet Boogaerts, Ramon Polo, Gaston Picchio, Maria Beumont
Journal: New England Journal of Medicine (2011)

Up to 60% of patients with hepatitis C virus (HCV) genotype 1 infection do not have a sustained virologic response to therapy with peginterferon alfa plus ribavirin.
Re-emergence of Chlamydia trachomatis infection after mass antibiotic treatment of a trachoma-endemic Gambian community: a longitudinal study
Authors: Matthew J Burton, Martin J Holland, Pateh Makalo, Esther AN Aryee, Neal DE Alexander, Ansumana Sillah, Hannah Faal, Sheila K West, Allen Foster, Gordon J Johnson, David CW Mabey, Robin L Bailey
Journal: The Lancet (2005)
Differences in Weight Loss Between Persons on Standard Balanced vs Nutrigenetic Diets in a Randomized Controlled Trial
Authors: Karen A. Frankwich, Jeremy Egnatios, Mandy L. Kenyon, Thomas R. Rutledge, Patricia S. Liao, Samir Gupta, Karen L. Herbst, Amir Zarrinpar
Journal: Clinical Gastroenterology and Hepatology (2015)
Expression of the zinc finger transcription factor zDC (Zbtb46, Btbd4) defines the classical dendritic cell lineage
Authors: Matthew M. Meredith, Kang Liu, Guillaume Darrasse-Jeze, Alice O. Kamphorst, Heidi A. Schreiber, Pierre Guermonprez, Juliana Idoyaga, Cheolho Cheong, Kai-Hui Yao, Rachel E. Niec, Michel C. Nussenzweig
Journal: The Journal of Experimental Medicine (2012)

Classical dendritic cells (cDCs), monocytes, and plasmacytoid DCs (pDCs) arise from a common bone marrow precursor (macrophage and DC progenitors [MDPs]) and express many of the same surface markers, including CD11c. We describe a previously uncharacterized zinc finger transcription factor, zDC (Zbtb46, Btbd4), which is specifically expressed by cDCs and committed cDC precursors but not by monocytes, pDCs, or other immune cell populations. We inserted diphtheria toxin (DT) receptor (DTR) cDNA into the 3′ UTR of the zDC locus to serve as an indicator of zDC expression and as a means to specifically deplete cDCs. Mice bearing this knockin express DTR in cDCs but not other immune cell populations, and DT injection into zDC-DTR bone marrow chimeras results in cDC depletion. In contrast to previously characterized CD11c-DTR mice, non-cDCs, including pDCs, monocytes, macrophages, and NK cells, were spared after DT injection in zDC-DTR mice. We compared immune responses to Toxoplasma gondii and MO4 melanoma in DT-treated zDC- and CD11c-DTR mice and found that immunity was only partially impaired in zDC-DTR mice. Our results indicate that CD11c-expressing non-cDCs make significant contributions to initiating immunity to parasites and tumors.
The comparison of effects of three types of resistance, endurance and concurrent training on amount of growth hormone secretion in active males
Authors: Amir Akbari, Hossein Mojtahedi, Fakhreddin Rajaei, Mohammad Marandi
Journal: British Journal of Sports Medicine (2010)

The main purpose of the present study was to compare the effects of three types of endurance (E), resistance (R) and combined (C) exercise on the rate of growth hormone (GH) secretion in active men. Fifteen healthy, active young men (mean age ± SD of 23 ± 1.604 years, height 173 ± 3.751 m, weight 69 ± 8.742 kg) were participated in research voluntarily. The same subjects were taking part in three types of exercise in three different time with 7-day interval among them. Blood samples taken before, immediately and 20 min after the exercise. t Test and analysis of variance were used to analyse the data (p&lt;0.01). Results show GH secretion rate increased significantly immediately and 20 min after exercise (E) and immediately after exercise (C) compared to pretest. There were no significantly increase in the rate of GH secretion 20 min after exercise (C), immediately and 20 min after exercise (R). There was no significant differences between the rate of GH secretion (immediately and 20 min after exercise) after E and C exercise and there was no significant difference between GH secretion immediately after exercise and 20 min after exercise (E, R, C). There were significant differences between GH secretion immediately and 20 min after exercise (E with R) and (C with R). Exercise directly leads to GH production changing pattern, which in turn results in creation of new tissues. It is believed that GH concentrations can change with exercise. The results of this research showed that GH concentrations was increased after endurance exercise (20 min and immediately after exercise compared to pretest), and combined exercise. It is generally concluded that various types of physical activity has a different effects on the GH responses.
Cyclophilin inhibition as potential therapy for liver diseases
Authors: Nikolai V. Naoumov
Journal: Journal of Hepatology (2014)

The cyclophilins are a group of proteins with peptidyl-prolyl isomerase enzymatic activity, localised in different cellular compartments and involved in a variety of functions related to cell metabolism and energy homeostasis, having enhanced expression in inflammation or malignancy. Cyclophilin A (CypA), the most abundantly expressed cyclophilin, is present mainly in the cytoplasm and is a host factor involved in the life cycle of multiple viruses. The extracellular fractions of CypA and CypB are potent pro-inflammatory mediators. CypD, located in mitochondria, is a key regulator of mitochondrial permeability transition pores, and is critical for necrotic cell death. Cyclosporines are the prototype cyclophilin inhibitors. Cyclic peptides, which bind and inhibit cyclophilins without having immunosuppressive properties, have been generated by chemical modifications of cyclosporin A. In addition, cyclophilin inhibitors that are structurally different from cyclosporines have been synthesized. The involvement of cyclophilins in the pathogenesis of different liver diseases has been established using both in vitro and in vivo investigations, thus indicating that cyclophilin inhibition may be of therapeutic benefit. This review summarises the evidence for potential therapeutic applications of non-immunosuppressive cyclophilin inhibitors, alone or in combination with other agents, in virus-induced liver diseases like hepatitis C, B or Delta, liver inflammation and fibrosis, acetaminophen-induced liver toxicity and hepatocellular carcinoma.
High-Resolution Intracellular Recordings Using a Real-Time Computational Model of the Electrode
Authors: Romain Brette, Zuzanna Piwkowska, Cyril Monier, Michelle Rudolph-Lilith, Julien Fournier, Manuel Levy, Yves Frégnac, Thierry Bal, Alain Destexhe
Journal: Neuron (2008)
Enteral ornithine α-ketoglutarate enhances intestinal adaptation to massive resection in rats
Authors: Frédéric Dumas, Jean Pascal De Bandt, Virginie Colomb, Jacques Le Boucher, Colette Coudray-Lucas, Sébastien Lavie, Nicole Brousse, Claude Ricour, Luc Cynober, Olivier Goulet
Journal: Metabolism (1998)
Downregulation of peptide transporter genes in cell lines transformed with the highly oncogenic adenovirus 12.
Authors: R Rotem-Yehudar, S Winograd, S Sela, J E Coligan, R Ehrlich
Journal: The Journal of Experimental Medicine (1994)

The expression of class I major histocompatibility complex antigens on the surface of cells transformed by adenovirus 12 (Ad12) is generally very low, and correlates with the high oncogenicity of this virus. In primary embryonal fibroblasts from transgenic mice that express both endogenous H-2 genes and a miniature swine class I gene (PD1), Ad12-mediated transformation results in suppression of cell surface expression of all class I antigens. Although class I mRNA levels of PD1 and H-2Db are similar to those in nonvirally transformed cells, recognition of newly synthesized class I molecules by a panel of monoclonal antibodies is impaired, presumably as a result of inefficient assembly and transport of the class I molecules. Class I expression can be partially induced by culturing cells at 26 degrees C, or by coculture of cells with class I binding peptides at 37 degrees C. Analysis of steady state mRNA levels of the TAP1 and TAP2 transporter genes for Ad12-transformed cell lines revealed that they both are significantly reduced, TAP2 by about 100-fold and TAP1 by 5-10-fold. Reconstitution of PD1 and H-2Db, but not H-2Kb, expression is achieved in an Ad12-transformed cell line by stable transfection with a TAP2, but not a TAP1, expression construct. From these data it may be concluded that suppressed expression of peptide transporter genes, especially TAP2, in Ad12-transformed cells inhibits cell surface expression of class I molecules. The failure to fully reconstitute H-2Db and H-2Kb expression indicates that additional factors are involved in controlling class I gene expression in Ad12-transformed cells. Nevertheless, these results suggest that suppression of peptide transporter genes might be an important mechanism whereby virus-transformed cells escape immune recognition in vivo.
Low-density lipoprotein receptor-deficient mice are protected against lethal endotoxemia and severe gram-negative infections.
Authors: M G Netea, P N Demacker, B J Kullberg, O C Boerman, I Verschueren, A F Stalenhoef, J W van der Meer
Journal: Journal of Clinical Investigation (1996)

Lipoproteins can bind lipopolysaccharide (LPS) and decrease the LPS-stimulated production of pro-inflammatory cytokines. We investigated the effect of increased plasma concentrations of low-density-lipoproteins (LDL) on survival and cytokine production after a lethal challenge with either LPS or live Gram-negative bacteria in LDL receptor deficient mice (LDLR-/-). The LDLR-/- mice challenged with LPS had an eightfold increased LD50 when compared with the wild type controls (C57Bl/6J), while tumor necrosis factor alpha (TNFalpha) and interleukin-1 alpha (IL-1 alpha) plasma concentrations were decreased twofold. LDLR-/- mice had significantly lower and delayed mortality than control mice after infection with Klebsiella pneumoniae. No differences in the outgrowth of bacteria in the organs were present between the two groups, while circulating cytokine concentrations were decreased twofold in LDLR-/- mice. In contrast, the LPS-stimulated in vitro production of cytokines by peritoneal macrophages of LDLR-/- mice was significantly increased compared with controls. This increase was associated with enhanced specific binding of LPS to the macrophages of LDLR-/- mice. In conclusion, endogenous LDL can protect against the lethal effects of endotoxin and Gram-negative infection. At least part of this protection is achieved through decreased in vivo production of pro-inflammatory cytokines, in spite of increased cytokine production capacity.
Extracorporeal methods of reducing high blood ammonia levels
Authors: H. D. Ritchie, D. M. Davies, J. M. Godfrey, P. Fan, R. G. S. Johns, J. Perrin
Journal: Gut (1962)

Laboratory studies have been made to evaluate two methods for removing ammonia from blood:— 1 The twin-coil artificial kidney was found to produce significant reductions in the ammonia content of outdated human banked blood. After one passage through the coil, levels of up to 9 μg. of ammonia nitrogen per millilitre were reduced to normal, and this effect was maintained when up to 5 litres were passed. 2 Ion-exchange resins, in particular a British resin ZK.225 having a 20% divinyl-benzene linkage, were also found to be effective. When passed from an artery directly through an autoclaved resin column to a vein, significant amounts of ammonia were removed from the blood of a dog with pronounced hyperammonaemia. No serious systemic, biochemical, or haematological effects were observed when the blood of three normal dogs was passed through resin columns. All survived, and to date no reason has been found why such a technique could not be used in clinical practice.
Changes in Health-Related Quality of Life in Patients with Primary Immunodeficiency Disorder (PIDD) Between Time of Diagnosis and 12 Months after Initiation of Immunoglobulin (Ig) Therapy
Authors: John M. Routes, Beatriz T.C. Carvalho, Bodo Grimbacher, Kenneth Paris, Hans D. Ochs, Alexandra H. Filipovich, Diane Ito, Yan Xiong, Josephine Li-McLeod, Patrick Bonnet
Journal: Journal of Allergy and Clinical Immunology (2015)
Aldosterone Directly Induces Myocyte Apoptosis Through Calcineurin-Dependent Pathways
Authors: Akiko Mano, Tetsuya Tatsumi, Jun Shiraishi, Natsuya Keira, Tetsuya Nomura, Mitsuo Takeda, Susumu Nishikawa, Satoshi Yamanaka, Satoaki Matoba, Miyuki Kobara, Hideo Tanaka, Takeshi Shirayama, Tetsuo Takamatsu, Yoshihisa Nozawa, Hiroaki Matsubara
Journal: Circulation (2004)

Background— Aldosterone has recently attracted considerable attention for its involvement in the pathophysiology of heart failure, in which apoptotic cell loss plays a critical role. This study examined whether aldosterone directly induces myocyte apoptosis via its specific receptors. Methods and Results— Neonatal rat cardiac myocytes were exposed to aldosterone (10 −8 to 10 −5 mol/L). Nuclear staining with Hoechst 33258 showed that aldosterone induced myocyte apoptosis in a dose- and time-dependent fashion. Treatment of myocytes with 10 −5 mol/L aldosterone significantly increased the percentage of apoptosis (15.5±1.4%) compared with serum-deprived control (7.3±0.6%). Radio ligand binding assay revealed the existence of plasma membrane receptor with high affinity ( K d , 0.2 nmol/L) for aldosterone in cardiac myocytes but not in fibroblasts. Aldosterone rapidly (≈30 seconds) mobilized [Ca 2+ ] i that was blocked by neomycin. Aldosterone induced dephosphorylation of the proapoptotic protein Bad, enhancement of mitochondrial permeability transition, decrease in mitochondrial membrane potential, and release of cytochrome c from the mitochondria into the cytosol with concomitant activation of caspase-3. These effects of aldosterone were inhibited by concurrent treatment with either an L-type Ca 2+ channel antagonist, nifedipine, or inhibitors for the Ca 2+ -dependent phosphatase calcineurin, cyclosporin A and FK506. Conclusions— The present study demonstrates for the first time that the specific plasma membrane receptor (coupled with phospholipase C) for aldosterone is present on cardiac myocytes and that aldosterone accelerates the mitochondrial apoptotic pathway through activation of calcineurin and dephosphorylation of Bad, suggesting that the proapoptotic action of aldosterone may directly contribute to the progression of heart failure.