tbuckley/cabot-search huggingface dataset:
Dissociation between systemic and mucosal humoral immune responses in coeliac disease.
Authors: S O'Mahony, E Arranz, J R Barton, A Ferguson
Journal: Gut (1991)

We examined humoral immunity in coeliac disease as expressed in serum (systemic immunity), and in saliva, jejunal aspirate, and whole gut lavage fluid (mucosal immunity). The aims were to define features of the secretory immune response (IgA and IgM concentrations and antibody values to gliadin and other food proteins measured by enzyme linked immunosorbent assay (ELISA)) in active disease and remission, and to establish whether secretions obtained by relatively non-invasive techniques (saliva and gut lavage fluid) can be used for indirect measurements of events in the jejunum. Serum, saliva, and jejunal aspirate from 26 adults with untreated coeliac disease, 22 treated patients, and 28 immunologically normal control subjects were studied, together with intestinal secretions obtained by gut lavage from 15 untreated and 19 treated patients with coeliac disease and 25 control subjects. Jejunal aspirate IgA and IgM and gut lavage fluid IgM concentrations were significantly raised in patients with untreated coeliac disease; the lavage fluid IgM concentration remained higher in patients with treated coeliac disease than in controls. Serum and salivary immunoglobulin concentrations were similar in the three groups. Patients with untreated coeliac disease had higher values of antibodies to gliadin compared with treated patients and control subjects in all body fluids tested; these were predominantly of IgA and IgG classes in serum, and of IgA and IgM classes in jejunal aspirate and gut lavage fluid. Values of salivary IgA antibodies to gliadin were significantly higher in untreated coeliacs, though antibody values were generally low, with a large overlap between coeliac disease patients and control subjects. In treated patients, with proved histological recovery on gluten free diet, serum IgA antigliadin antibody values fell to control values, though serum IgG antigliadin antibody values remained moderately raised. In contrast, there was persistence of secretory antigliadin antibodies in treated patients (particularly IgM antibody) in both jejunal aspirate and gut lavage fluid. Antibody responses to betalactoglobulin and ovalbumin were similar to those for gliadin, including persistence of high intestinal antibody values in patients with treated coeliac disease. There was a positive correlation between antibody values in jejunal aspirate and gut lavage fluid, but not between saliva and jejunal aspirate; thus salivary antibodies do not reflect intestinal humoral immunity.
Hypothesis: Does COPD have an autoimmune component?
Authors: A Agusti
Journal: Thorax (2003)

A new hypothesis that considers the role of the immune system in the pathogenesis of COPD is explored which, if true, will generate new therapeutic opportunities in this condition.

Chronic obstructive pulmonary disease (COPD) is a major public health problem because: (1) it causes significant morbidity and mortality which is expected to increase worldwide in the near future;1 (2) it jeopardises the quality of life of the patients suffering from this devastating disease (particularly during exacerbations);2,3 and (3) it imposes an enormous global healthcare cost.1 However, because the pathogenesis of COPD is poorly understood, treatment is mostly symptomatic and new therapeutic strategies are limited.4 In this paper we propose a new hypothesis that considers the largely unexplored role of the immune system in the pathogenesis of COPD. If true, this hypothesis will generate new therapeutic opportunities in COPD.

The Global initiative for the diagnosis, management, and prevention of Obstructive Lung Disease (GOLD) defines COPD as a “disease state which is usually both progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases”.5 Many studies have attempted to characterise this abnormal inflammatory response. However, this issue is far from resolved because the results of these studies vary according to the severity of the disease (mild, moderate, or severe), the type of controls studied (never smokers, smokers with normal lung function, patients with stable COPD compared with those studied during exacerbations of the disease), the compartment of the lung sampled (central airways, peripheral airways, alveolar space), and/or the bias of the study towards the role of a given cell type.6 A critical review of this literature7 indicates the following salient features: (1) all smokers develop airway inflammation; (2) this is amplified in patients with COPD, particularly during exacerbations …
The role of cysteinyl leukotrienes (CysLTS) in bone marrow responses in murine experimental allergic rhinitis: Blockade of eosinophil production and tissue eosinophilia by a CysLT1 receptor antagonist
Authors: H. Saito, L. Crawford, E. Denburg, J.A. Denburg
Journal: Journal of Allergy and Clinical Immunology (2003)
Angiotensin-converting enzyme inhibitor fetopathy.
Authors: P G Pryde, A B Sedman, C E Nugent, M Barr
Journal: Journal of the American Society of Nephrology (1993)

Angiotensin-converting enzyme (ACE) inhibitors are widely used for controlling hypertension. Their use in women who are pregnant is not without risk to the fetus. We describe three infants exposed in utero to ACE inhibitors who had adverse outcomes. These cases, combined with other reports in the literature, suggest strongly that these drugs are fetotoxic. ACE inhibitor fetopathy is characterized by fetal hypotension, anuria-oligohydramnios, growth restriction, pulmonary hypoplasia, renal tubular dysplasia, and hypocalvaria. Although the true frequency of adverse fetal effects has yet to be determined, because of the debilitating and lethal nature of the fetal damage when it occurs, it is our recommendation that ACE inhibitors not be used in pregnancy, particularly in the second and third trimesters.
STUDIES ON EXPERIMENTAL SHIGELLOSIS
Authors: C. David McGuire, Thomas M. Floyd
Journal: The Journal of Experimental Medicine (1958)

Host resistance to Shigella infections can be decreased by non-specific physical stress. Fasting lowers the number of Shigella required for a parenteral LD(50) dose. While the LD(50) by the oral route is larger in fasted than in nonfasted animals, the fasted host's susceptibility to oral infection is increased as evidenced by the increased fecal Shigella carrier state, duration of intestinal infection, and increased incidence of Shigella bacteriemia. Fatigue also increases the animal's susceptibility to shigellosis, but to a lesser extent than does fasting.
Immunohistochemical Detection of Hypoxia-Inducible Factor-1α in Human Renal Allograft Biopsies
Authors: Christian Rosenberger, Johann Pratschke, Birgit Rudolph, Samuel N. Heyman, Ralf Schindler, Nina Babel, Kai-Uwe Eckardt, Ulrich Frei, Seymour Rosen, Petra Reinke
Journal: Journal of the American Society of Nephrology (2006)

Although it generally is accepted that renal hypoxia may occur in various situations after renal transplantation, direct evidence for such hypoxia is lacking, and possible implications on graft pathophysiology remain obscure. Hypoxia-inducible factors (HIF) are regulated at the protein level by oxygen-dependent enzymes and, hence, allow for tissue hypoxia detection. With the use of high-amplification HIF-1alpha immunohistochemistry in renal biopsies, hypoxia is shown at specific time points after transplantation with clinicohistologic correlations. Immediately after engraftment, in primarily functioning grafts, abundant HIF-1alpha is present and correlates with cold ischemic time >15 h and/or graft age >50 yr (P < 0.04). In contrast, a low HIF-1alpha score correlates with primary nonfunction, likely reflecting loss of oxygen consumption for tubular transport. Protocol biopsies at 2 wk show widespread HIF-1alpha induction, irrespective of histology. Beyond 3 mo, both protocol biopsies and indicated biopsies are virtually void of HIF-1alpha, with the only exception being clinical/subclinical rejection. HIF-derived transcriptional adaptation to hypoxia may counterbalance, at least partly, the negative impact of cold preservation and warm reflow injury. Transient hypoxia at 2 wk may be induced by hyperfiltration, hypertrophy, calcineurin inhibitor-induced toxicity, or a combination of these. Lack of detectable HIF-1alpha at 3 mo and beyond suggests that at this time point, graft oxygen homeostasis occurs. The strong correlation between hypoxia and clinical/subclinical rejection in long-term grafts suggests that hypoxia is involved in such graft dysfunction, and HIF-1alpha immunohistochemistry could enhance the specific diagnosis of acute rejection.
Exome sequencing to identify de novo mutations in sporadic ALS trios
Authors: Alessandra Chesi, Brett T Staahl, Ana Jovičić, Julien Couthouis, Maria Fasolino, Alya R Raphael, Tomohiro Yamazaki, Laura Elias, Meraida Polak, Crystal Kelly, Kelly L Williams, Jennifer A Fifita, Nicholas J Maragakis, Garth A Nicholson, Oliver D King, Robin Reed, Gerald R Crabtree, Ian P Blair, Jonathan D Glass, Aaron D Gitler
Journal: Nature Neuroscience (2013)
Quality Control for Spirometry in Preschool Children with and without Lung Disease
Authors: Paul Aurora, Janet Stocks, Cara Oliver, Clare Saunders, Rosemary Castle, Greg Chaziparasidis, Andrew Bush
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

The reliability of spirometry is dependent on strict quality control. We examined whether quality control criteria recommended for adults could be applied to children aged 2-5 years. Forty-two children with cystic fibrosis and 37 healthy children attempted spirometry during their first visit to our laboratory. Whereas 59 children (75%) were able to produce a technically satisfactory forced expiration lasting 0.5 second, only 46 (58%) could produce an expiration lasting 1 second, with the youngest children having the most difficulty. Start of test criteria for adults were inappropriate for this age group, with only 16 of 59 children producing a volume of back extrapolation as a proportion of forced vital capacity of less than 5%, whereas all but 4 could produce a volume of back extrapolation of 80 ml or less. More than 90% of children were able to produce a second forced vital capacity and a second forced expired volume in 0.75 second within 10% of their highest. Errors in the spirometry software resulted in inaccurate reporting of expiratory duration and inappropriate timed expired volumes in some children. We describe recommendations for modified start of test and repeatability criteria for this age group, and for improvements in software to facilitate better quality control.
Magnesium sulfate for neuroprotection after traumatic brain injury: a randomised controlled trial
Authors: Nancy R Temkin, Gail D Anderson, H Richard Winn, Richard G Ellenbogen, Gavin W Britz, James Schuster, Timothy Lucas, David W Newell, Pamela Nelson Mansfield, Joan E Machamer, Jason Barber, Sureyya S Dikmen
Journal: The Lancet Neurology (2006)
Cardiac Graft Intercellular Adhesion Molecule-1 (ICAM-1) and Interleukin-1 Expression Mediate Primary Isograft Failure and Induction of ICAM-1 in Organs Remote From the Site of Transplantation
Authors: Catherine Y. Wang, Yoshifumi Naka, Hui Liao, Mehmet C. Oz, Timothy A. Springer, Jose-Carlos Gutierrez-Ramos, David J. Pinsky
Journal: Circulation Research (1998)

Abstract —During the first few hours after heart transplantation, the occurrence of graft failure is unpredictable and devastating. An explosive cascade of inflammatory events within the reperfused graft vasculature is likely to be mediated, at least in part, by the local expression of the leukocyte adhesion receptor intercellular adhesion molecule-1 (ICAM-1, CD54). Furthermore, although proinflammatory cytokines such as interleukin-1 (IL-1) are known to autoinduce their own (and ICAM-1) expression in vitro, there are no data to identify their functional in vivo cross talk in the setting of isograft transplantation. To determine the role of ICAM-1 in primary graft failure, we used an isogeneic vascularized model of heterotopic cardiac transplantation. ICAM-1 mRNA and protein increased in grafts during the early posttransplant period and were predominantly localized in the endothelium. The functional significance of this was established using donor hearts obtained from either ICAM-1–deficient (ICAM-1 −/−) or control (ICAM-1 +/+) mice. ICAM-1 +/+ grafts exhibited increased neutrophil infiltration, reduced left ventricular compliance, and poorer survival than did ICAM-1 −/− grafts. Increased ICAM-1 expression was not limited to ICAM-1 +/+ grafts but also occurred in unmanipulated recipient organs located remote from the site of surgery (but only after transplantation of ICAM-1 +/+, not ICAM-1 −/−, cardiac grafts). This expression of ICAM-1 in remote organs appeared to be triggered by IL-1α released from the graft, because (1) in situ hybridization revealed increased IL-1 mRNA within cells of the reperfused graft, including myocytes and endothelial cells; (2) ICAM-1 expression in remote organs coincided with a significant increase in serum levels of IL-1α after transplantation of ICAM-1 +/+ grafts; both remote organ ICAM-1 expression and IL-1α levels were blunted by implantation of ICAM-1 −/− grafts; and (3) remote organ ICAM-1 expression and neutrophil infiltration and IL-1 levels could be blocked by the administration of an IL-1 receptor antagonist. These data demonstrate an apparent positive-feedback loop in which local ICAM-1 and IL-1 expression leads to a mutual amplification of each other’s expression within the reperfused graft, promulgating inflammatory events that are likely to be an important cause of primary cardiac graft failure. Because IL-1 receptor blockade reduces the IL-1–mediated autoinduction of IL-1, reduces the expression of ICAM-1 in both the graft and remote organs, and improves graft survival, it may provide a new and effective strategy to prevent the occurrence of primary cardiac graft failure.
Staphylococcal pneumonia, pneumatoceles, and the toxic shock syndrome.
Authors: A C Davidson, M Creach, I R Cameron
Journal: Thorax (1990)

A case of community acquired staphylococcal pneumonia is reported with the unusual complication, in an adult, of multiple pneumatoceles. Recognition of this prevented inappropriate management. The patient also developed the toxic shock syndrome. In contrast to infants with pneumatoceles, recovery of lung function has been poor.
Distribution Maps of Esophageal Cancer Among Bantu in the Transkei&lt;xref ref-type="fn" rid="FN1"&gt;1&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: R J Burrell
Journal: JNCI Journal of the National Cancer Institute (1969)

The maps in this report incorporate the results of a 5-year survey of esophageal cancer among South African Bantu domiciled in reserves of the Transkeian Territories. Available information suggests that the disease was unknown 25 years ago; today, however, esophageal cancer is particularly rife in scattered circumscribed localities. The population investigated was 1.6 million, of which 1,882 patients were registered—1,036 men and 846 women. Sixty percent of cases were diagnosed as esophageal cancer on irrefutable radiological evidence, and about one-third were confirmed as squamous carcinoma by biopsy or cytological examinations. The remaining 40% were diagnosed on clinical grounds only. Most of the tumors were in the middle-third esophagus, but in older patients relatively more were in the lower third. Crude morbidity and mortality rates are given, as well as mortality rates for males and females in half-decade age groups. Females show a peak mortality at 50 years of age, whereas the mortality curve for males continues to rise steeply to 60 years and beyond.
Evolutionary and Functional Evidence for Positive Selection at the Human CD5 Immune Receptor Gene
Authors: E. Carnero-Montoro, L. Bonet, J. Engelken, T. Bielig, M. Martinez-Florensa, F. Lozano, E. Bosch
Journal: Molecular Biology and Evolution (2011)

CD5 is a lymphocyte surface coreceptor of still incompletely understood function. Currently available information indicates that CD5 participates not only in cell-to-cell immune interactions through still poorly defined endogenous ligands expressed on hemopoietic and nonhemopoietic cells but also in recognition of exogenous and highly conserved microbial structures such as fungal β-glucans. Preceding single nucleotide polymorphism (SNP) data analysis provided evidence for a recent selective sweep in East Asia and suggested a nonsynonymous substitution at position 471 (A471V; rs2229177) of the cytoplasmatic region of the CD5 receptor as the most plausible target of selection. The present report further investigates the role of natural selection in the CD5 gene by a resequencing approach in 60 individuals representing populations from 3 different continents (20 Africans, 20 Europeans and 20 East Asians) and by functionally assaying the relevance of the A471V replacement on CD5 signaling. The high differentiation pattern found at the nonsynonymous A471V site together with the low diversity, most of the performed neutrality tests (Tajima's D, Fu and Li's F* and D*, and Fu's Fs) and the predominance of a major haplotype in East Asians strongly argue in favor of positive selection for the A471V site. Importantly, anti-CD5 monoclonal antibody cross-linking unveiled significant differences among A471V variants regarding the mitogen-activated protein kinase (MAPK) cascade activation on COS7 and on human peripheral blood mononuclear cells. Similar differences on MAPK activation and IL-8 cytokine release were also observed upon exposure of HEK293 cell transfectants expressing the A471V variants to Zymosan, a β-glucan-rich fungal particle. Taken together, the results provide evidence for the hypothesis of an adaptive role of the A471V substitution to environmental challenges, most likely infectious pathogens, in East Asian populations.
mTOR Inhibitors Induce Cell-Cycle Arrest and Inhibit Tumor Growth in Epstein–Barr Virus–Associated T and Natural Killer Cell Lymphoma Cells
Authors: Jun-ichi Kawada, Yoshinori Ito, Seiko Iwata, Michio Suzuki, Yoshihiko Kawano, Tetsuhiro Kanazawa, Mohammed Nure Alam Siddiquey, Hiroshi Kimura
Journal: Clinical Cancer Research (2014)

Epstein-Barr virus (EBV) infects B cells, as well as T cells and natural killer (NK) cells, and is associated with T or NK cell lymphoid malignancies. In various tumor cells, mTOR performs an essential function together with Akt with regard to cell growth. We investigated the effects of mTOR inhibitors on EBV-associated T- and NK-cell lymphomas.We investigated the Akt/mTOR activation pathway in EBV-positive and -negative T- and NK-cell lines (SNT13, SNT16, Jurkat, SNK6, KAI3, and KHYG1). We evaluated the antitumor effects of mTOR inhibitors (rapamycin and its analogue, CCI-779) against these cell lines in culture and in a murine xenograft model that was established by subcutaneous injection of SNK6 cells into NOG mice.All EBV-positive and -negative T- and NK-cell lines tested displayed activation of the Akt/mTOR pathway, and treatment with mTOR inhibitors suppressed mTOR activation. The inhibitors induced G1 cell-cycle arrest and inhibited cell proliferation in T- and NK-cell lines. Overall, T cell lines were more sensitive to rapamycin, but there were no significant differences between EBV-positive and -negative cell lines. Treatment with rapamycin did not affect lytic or latent EBV gene expression. Intraperitoneal treatment with CCI-779 significantly inhibited the growth of established tumors in NOG mice and reduced the EBV load in peripheral blood.These results suggest that inhibition of mTOR signaling is a promising new strategy for improving treatment of EBV-associated T- and NK-cell lymphoma.
Rapid diagnosis of anaerobic infections by direct gas-liquid chromatography of clinical speciments.
Authors: S L Gorbach, J W Mayhew, J G Bartlett, H Thadepalli, A B Onderdonk
Journal: Journal of Clinical Investigation (1976)

Current methods to isolate and identify anaerobic bacteria are laborious and time consuming. It was postulated that the short-chain fatty acids (SCFA) produced by these organisms might serve as microbial markers in clinical material. 98 specimens of pus or serous fluid were analyzed by gas-liquid chromatography, and findings were compared with culture results. Good correlations were found for the recovery of anaerobic Gram-negative bacilli and the presence of isobutyric, butyric, and succinic acids. 19 of 20 specimens with significant amounts of these acids (greater than 0.01 mumol/ml) yielded bacteroides or fusobacteria. Culture of the single "false-positive" specimen failed to grow anaerobic Gram-negative bacilli, although clinical data and Gram-stain suggested their presence. 77 of 78 specimens which has insignificant concentrations of the marker acids failed to yield anaerobic, Gram-negative bacilli in culture. The single "false-negative" specimen yielded Bacteroides pneumosintes, an organism which does not ferment carbohydrates. It is concluded that direct gas-liquid chromatographic analysis of clinical specimens provides a rapid presumptive test for the presence of anaerobic, Gram-negative bacilli.
The HDAC Inhibitor LBH589 Enhances the Antimyeloma Effects of the IGF-1RTK Inhibitor Picropodophyllin
Authors: Miguel Lemaire, Charlotte Fristedt, Prasoon Agarwal, Eline Menu, Els Van Valckenborgh, Elke De Bruyne, Anders Österborg, Peter Atadja, Olle Larsson, Magnus Axelson, Ben Van Camp, Helena Jernberg-Wiklund, Karin Vanderkerken
Journal: Clinical Cancer Research (2012)

We have previously shown the use of the insulin-like growth factor type 1 receptor tyrosine kinase (IGF-1RTK) inhibitor picropodophyllin (PPP) as an attractive strategy to combat multiple myeloma (MM) in vitro and in vivo. After a combinatorial drug screening, the histone deacetylase inhibitor LBH589 was shown to act in synergy with PPP reducing survival of MM cells. In this study, we tried to elucidate the molecular mechanisms underlying this combinatorial effect.The in vitro anti-MM effects of PPP and LBH589 alone and in combination were evaluated by studying apoptosis, cell cycle distribution, and downstream transcriptome using both human MM cell lines and cells from the murine 5T3MM model. In vivo the effect on survival of 5T33MM-inoculated mice was evaluated.In the human MM cell line RPMI8226, treatment with PPP and LBH589 in combination resulted in a five-fold increase of apoptosis, and an additive effect on the cleavage of the active forms of caspase-8 was observed as compared with the single drug treatments. Cell cycle analysis revealed an accumulation of cells in the G(2)-M phase and subsequent downregulation of cell cycle regulating proteins. These data were also confirmed in the 5T33MM cells in vitro. Also, the transcriptome was analyzed by Affymetrix arrays showing gene expression alterations mainly in categories of genes regulating apoptosis and cell adhesion. Combined treatment in vivo resulted in a significantly prolonged survival of 5T33MM-inoculated mice.The results indicate an improved MM treatment opportunity in using a combination of PPP and LBH589.