tbuckley/cabot-search huggingface dataset:
Early kinetics of innate and adaptive immune responses during hepatitis B virus infection
Authors: P Fisicaro, C Valdatta, C Boni, M Massari, C Mori, A Zerbini, A Orlandini, L Sacchelli, G Missale, C Ferrari
Journal: Gut (2009)

<h3>Background and Aim:</h3> Innate immunity appears to be silent in acutely heptitis B virus (HBV)-infected chimpanzees, as shown by microarray analysis of intrahepatic gene expression. Whether this observation also applies to HBV pathogenesis in man remains undefined. The aim of this study was thus to characterise natural killer (NK) and CD56<sup>+</sup> natural T (NT) cell responses early after human HBV infection and their relationship to the induction of adaptive immunity. <h3>Methods:</h3> Two HBV-seronegative blood donors who became hepatitis B surface antigen (HBsAg) and HBV DNA positive but had persistently normal alanine aminotransferase (ALT) were followed from a very early stage of HBV infection. The phenotype (CD69 and NKG2D) and function (cytotoxicity and interferon γ (IFNγ) production) of NK and NT cells were analysed. CD4- and CD8-mediated responses were studied in parallel with overlapping peptides covering the entire HBV sequence by ex vivo intracellular cytokine staining (ICS) for IFNγ, interleukin 2 (IL2), IL4 and IL10, and by ex vivo Elispot for IFNγ. Healthy subjects, and patients with chronic and acute HBV infection were studied for comparison. <h3>Results:</h3> An early induction of both innate and adaptive responses was observed. NK and NT cells showed faster kinetics than HBV-specific T cells with an earlier peak of activity, while CD4<sup>+</sup> and CD8<sup>+</sup> cell responses were mounted with a similar profile, with higher frequencies of IFNγ-producing CD8<sup>+</sup> cells at the peak of the response. <h3>Conclusions:</h3> The innate immune system is able to sense HBV infection, as shown by the early development of NK and NT cell responses, which probably contribute to contain the HBV infection and to allow timely induction of adaptive responses.
The pleural space and organ transplantation.
Authors: M A Judson, S A Sahn
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Pleural disease both before and after organ transplantation has important implications. Pleural effusions are common in candidates for heart, liver, and kidney transplantation. A thoracentesis is not mandatory in these patients, but it should be performed if clinical or radiologic features suggest that the effusion is not the result of organ failure. Posttransplant pleural infections and pleural PTLD relate to the level and duration of immunosuppression and are probably not organ-specific. Organ-specific pleural complications include pleural effusion from hepatic venoocclusive disease, spontaneous pneumothorax associated with obstructive airway disease from chronic GVHD after bone marrow transplantation, and early pleural effusion from urinothorax and late effusion from perirenal lymphocele years after kidney transplantation. The treatment of pleural disease in potential lung transplant candidates should minimize the extent of pleurodesis. Pleural effusions are expected sequelae after lung transplantation, and they may be harbingers of acute rejection. Interpleural communication, an expected finding after heart-lung transplantation or double-lung transplantation with a "clamshell" incision, has therapeutic implications.
A possible relationship to treatment between hepatitis-associated antigen and chronic persistent hepatitis in Hodgkin's disease
Authors: M. J. Grange, S. Erlinger, F. Teillet, N. Schlegel, J. Barge, C. Degott
Journal: Gut (1973)

Hepatitis-associated (Australia) antigen (HAA) was detected in the sera of 16 (50%) of 33 patients with Hodgkin9s disease; all of these patients had received the same treatment for approximately two years, and they had been in complete remission for at least two years. The HAA-positive patients had significantly higher levels of serum SGPT and significantly lower bromsulphalein clearance than the HAA-negative patients. Histological changes compatible with a diagnosis of chronic persistent hepatitis were found in the livers of 12 of the 16 HAA-positive patients and in five of the 17 HAA-negative patients (p &lt; 0.05). In 128 patients with Hodgkin9s disease who had received various forms of treatment and who were studied at various stages of remission, HAA was found in the sera of 42 (33%). Tests for HAA repeated four months later in positive reactors of both groups showed persisting antigenaemia. Hepatitis-associated antigen was not present in the sera of any of 36 patients with Hodgkin9s disease studied when the diagnosis was first made and before treatment had begun. These observations suggest that persistence of HAA and the presence of chronic persistent hepatitis were more likely to be related to the treatment the patients had received than to the disease itself.
Cancer and Leukemia Group B Breast Committee: Decades of Progress and Plans for the Future
Authors: Clifford A. Hudis, Eric P. Winer
Journal: Clinical Cancer Research (2006)

Abstract The Breast Committee of the Cancer and Leukemia Group B was formed in 1969 under the direction of James Holland. Initial studies examined combination chemotherapy for advanced disease. Although the committee has continued to conduct studies in patients with advanced disease, adjuvant therapy has been an even more important focus for the past 30 years. Over the past 20 years, studies have focused on optimization of chemotherapy through the testing of dose and schedule, the value of adding novel agents, and the role of biological agents. Current and future projects are aimed at exploiting and increasing our growing knowledge of the molecular biology of breast cancer by developing targeted therapies.
Genomic analyses facilitate identification of receptors and signalling pathways for growth differentiation factor 9 and related orphan bone morphogenetic protein/growth differentiation factor ligands
Authors: Sabine Mazerbourg, Aaron J.W. Hsueh
Journal: Human Reproduction Update (2006)

Recent advances in genomic sequencing allow a new paradigm in hormonal research, and a comparative genomic approach facilitates the identification of receptors and signalling mechanisms for orphan ligands of the transforming growth factor b (TGFb) superfamily.Instead of purifying growth differentiation factor 9 (GDF9) receptor proteins for identification, we hypothesized that GDF9, like other ligands in the TGFb family, activates type II and type I serine/threonine kinase receptors.Because searches of the human genome for genes with sequence homology to known serine/threonine kinase receptors failed to reveal uncharacterized receptor genes, GDF9 likely interacts with the known type II and type I activin receptor-like kinase (ALK) receptors in granulosa cells.We found that co-treatment with the bone morphogenetic protein (BMP) type II receptor (BMPRII) ectodomain blocks GDF9 activity.Likewise, in a GDF9-non-responsive cell line, overexpression of ALK5, but none of the other six type I receptors, conferred GDF9 responsiveness.The roles of BMPRII and ALK5 as receptors for GDF9 were validated in granulosa cells using gene 'knock-down' approaches.Furthermore, we demonstrated the roles of BMPRII, ALK3 and ALK6 as the receptors for the orphan ligands GDF6, GDF7 and BMP10.Thus, evolutionary tracing of polypeptide ligands, receptors and downstream signalling molecules in their respective 'subgenomes' facilitates a new approach for hormonal research.
COMPENSATORY HYPERTROPHY OF THE THYMUS GLAND IN THE RAT
Authors: J. Marmorston-Gottesman, Henry L. Jaffe
Journal: The Journal of Experimental Medicine (1925)

Previous experimental work concerning enlargement of the thymus has dealt mainly with the regeneration which follows partial or subtotal removal, or with the regeneration which follows transplantation. We planned our experiments to obtain evidence of uncomplicated hypertrophy by removing one lobe and studying the enlargement of the remaining lobe. Our results clearly indicate that such hypertrophy takes place in young animals. They emphasize the functional importance of this gland before puberty, since the compensatory enlargement does not take place after puberty. The results further indicate that with the onset of involution there is a marked or almost total decline in the function of the gland, in spite of the fact that anatomically the thymus may persist to old age. With the appearance of a stimulus for regeneration, as, for instance, suprarenalectomy, the involuted gland takes on functional activity.
Bronchodilator response to salbutamol after chronic dosing with salmeterol or placebo
Authors: SJ Langley, CM Masterson, EP Batty, A Woodcock
Journal: European Respiratory Journal (1998)

It has been hypothesized that regular inhaled beta2-agonist therapy causes desensitization of beta2-receptors. The aim of this study was to define whether beta2-receptor desensitization occurs after treatment with the long-acting beta2-agonist salmeterol, assessed by measuring the bronchodilator response to cumulative repeated doses of inhaled salbutamol before and after treatment. Forty nine stable adult patients with asthma were randomized to receive either salmeterol 50 microg b.d. or placebo b.d. from an Accuhaler for 4 weeks after an initial 2 week run-in period without beta2-agonists. All patients were receiving inhaled corticosteroids. Bronchodilator responsiveness to cumulative repeated doses of inhaled salbutamol were measured before and 12 and 36 h after the last dose of study treatment. The primary efficacy endpoint was the peak forced expiratory volume in one second (FEV1) response before and after treatment. There were no significant differences between the two treatment groups in the absolute peak FEV1 or maximal peak expiratory flow (PEF) results 12 or 36 h after the last dose of study treatment. Significantly higher clinic lung function and diary card parameters were noted in the salmeterol group when compared to the placebo-treated patients, demonstrating the beneficial effects of regular salmeterol. Regular salmeterol usage did not lead to reduced efficacy of usual or higher than usual doses of salbutamol.
Mold insurance: crafting coverage for a spreading problem.
Authors: Julia R Barrett
Journal: Environmental Health Perspectives (2003)

Mold contamination is a growing concern for homeowners in terms of both physical health and insurance. Health experts, although they concede that exposure to mold can cause respiratory illnesses, are calling for further research into other mold-related health effects and for development of standards for mold sampling and data analysis. The insurance industry is grappling with how---and whether---to provide coverage for household damage caused by mold, while some state and federal legislators are working to pass laws regarding mold testing and insurance.
Urine glycoprotein crystal growth inhibitors. Evidence for a molecular abnormality in calcium oxalate nephrolithiasis.
Authors: Y Nakagawa, V Abram, J H Parks, H S Lau, J K Kawooya, F L Coe
Journal: Journal of Clinical Investigation (1985)

One reason that some people are prone to calcium oxalate nephrolithiasis is that they produce urine that is subnormal in its ability to inhibit the growth of calcium oxalate crystals. We have identified in human urine a glycoprotein (GCI) that inhibits calcium oxalate crystal growth strongly, and at low concentrations (10(-7) M); in this study, we have isolated GCI molecules from the urine of normal people and patients with calcium oxalate stones. GCI from stone formers is abnormal in three ways: it contains no detectable gamma-carboxyglutamic acid (Gla), whereas normal GCI contains 2-3 residues of Gla per mole; about half of the GCI in urine of patients inhibits crystal growth 4-20 times less than normal GCI as judged by its performance in a kinetic growth assay, in vitro; at the air-water interface, patient GCI has a film collapse pressure approximately half of normal. GCI molecules from the urine of patients with calcium oxalate nephrolithiasis are intrinsically abnormal, and these abnormalities could play a role in the genesis of stones.
Pneumococcal conjugate vaccine-induced regulatory T cells suppress the development of allergic airways disease
Authors: A. N. Thorburn, B. J. O'Sullivan, R. Thomas, R. K. Kumar, P. S. Foster, P. G. Gibson, P. M. Hansbro
Journal: Thorax (2010)

<h3>Background</h3> Infections with some bacteria, including <i>Streptococcus pneumoniae</i>, have been associated with a reduced incidence of asthma. Components of <i>S pneumoniae</i> may have the potential to modulate allergic inflammatory responses and suppress the development of asthma. <h3>Objectives</h3> To determine if human <i>S pneumoniae</i> vaccines have the potential to suppress asthma by elucidating their effect on allergic airways disease (AAD) in mouse models. <h3>Methods</h3> AAD was induced in BALB/c mice by intraperitoneal sensitisation and intranasal challenge with ovalbumin. Pneumococcal conjugate or polysaccharide vaccines were administered at the time of sensitisation or during established AAD. Hallmark features of AAD were assessed. Levels of regulatory T cells (Tregs) were quantified by fluorescence-activated cell sorting, and their immunoregulatory capacity was assessed using proliferation assays and anti-CD25 antibody treatment. <h3>Results</h3> Intranasal administration of the conjugate vaccine, but not the polysaccharide vaccine, suppressed the hallmark features of AAD, including: eosinophilic and T helper 2-mediated inflammation; airway hyper-responsiveness; circulating immunoglobulin E (IgE) levels; and mucus hypersecretion. Intramuscular administration of the conjugate vaccine had limited protective effects. The conjugate vaccine increased Tregs in the lung-draining lymph nodes, lung and spleen. Furthermore, conjugate vaccine-induced Tregs had an enhanced capacity to suppress T effector responses. Anti-CD25 administration reversed the suppressive effects of the conjugate vaccine. <h3>Conclusions</h3> A currently available human conjugate vaccine suppresses the hallmark features of AAD through the induction of Tregs. Thus targeted administration may provide a novel immunoregulatory treatment for asthma.
The level of maternal methemoglobin during pregnancy in an air-polluted environment.
Authors: Lucijan Mohorovic
Journal: Environmental Health Perspectives (2003)

The objective of this prospective study was to determine if a correlation could be established between the ground-level concentrations of sulfur dioxide and methemoglobin concentrations in pregnant women when a coal-powered thermoelectric power plant was in operation ("dirty" period) and when it was closed ("clean" period). The location of the power plant, Plomin 1, in Labin, Croatia, was taken into consideration. Blood and urine samples of each pregnant woman in the study were tested three times in the clean period (n = 138) and three times in the dirty period (n = 122), with 1 month between each test. I observed a correlation between the increase in mean values of methemoglobin and the ground-level concentration of SO(2) on corresponding dates during the dirty period (r = 0.72, p < 0.01). In the clean period, the negative mean value of methemoglobin was significant (r = -0.60, p <or=0.05), whereas in the dirty period, the positive mean value of methemoglobin was significant (r = 0.73, p 0.01). The increase of maternal methemoglobin could be a useful biomarker to determine when the health of pregnant women is threatened by toxic substances in the environment.
Eosinophils Are Dispensable for Allergic Remodeling and Immunity in a Model of House Dust Mite–induced Airway Disease
Authors: Ramzi Fattouh, Amal Al-Garawi, Marcia Fattouh, Katherine Arias, Tina D Walker, Susanna Goncharova, Anthony J Coyle, Alison A Humbles, Manel Jordana
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Current thinking accredits eosinophils with preeminent contributions to allergic airway responses, including a major role in the development of airway remodeling, a process thought to significantly contribute to airway dysfunction. However, direct evidence in support of this notion is limited and often controversial.We elucidated the requirement for eosinophils in the generation of allergic sensitization, airway inflammation, and remodeling in a model involving chronic respiratory exposure to house dust mite (HDM).We used three methods to selectively eliminate eosinophils, a depleting antibody (anti-CCR3), and two strains of eosinophil-deficient mice (ΔdblGATA and the transgenic line PHIL).Anti-CCR3 treatment markedly reduced pulmonary eosinophilia (> 80%) over the course of HDM exposure but had no effect on the remaining inflammatory response, the extent of lung Th2 cells, or the development of remodeling-associated changes, including subepithelial collagen deposition and smooth muscle thickening. In addition, we observed that, despite the absence of eosinophils, HDM-exposed GATA mice mounted robust airway and lung inflammation and hyperresponsiveness and showed a remodeling response equivalent to that observed in wild-type mice. Moreover, these mice had similar serum HDM-specific IgE levels and Th2-associated splenocyte cytokine production as HDM-exposed wild-type control mice. Similar observations were made in PHIL eosinophil-deficient mice subjected to chronic HDM exposure, although slight decreases in airway mononuclear cells, but not lung Th2 cells, and remodeling were noted.Collectively, these data demonstrate that, at variance with the prevailing paradigm, eosinophils play negligible roles in the generation of HDM-induced allergic immunity and airway remodeling.
Home Transfusions of Hemophiliacs
Authors: S. Frederick Rabiner
Journal: JAMA (1972)

We have had three years' experience with a home transfusion program for hemophiliacs. The group consisted of 36 patients, of which 32 had antihemophilic factor deficiency and 4 had plasma thromboplastin component deficiency. There were minimal technical problems and no serious transfusion reactions. Although there was an increase in the number of reported hemorrhages, there was a concomitant decrease in the number of hospital admissions. Of importance is the fact that there was a decrease in the number of severe orthopedic problems and days lost from school or work. Of equal importance was the psychological impact of home transfusion on patients and their families. This included a sense of self-reliance, an increase in mobility, and freedom from fear. The authors conclude that, until a prophylactic regimen is feasible, home transfusion is the treatment of choice for hemophilia.
Pressure and Angiotensin II Synergistically Induce Aortic Fibronectin Expression in Organ Culture Model of Rabbit Aorta
Authors: Nathalie Bardy, Re´gine Merval, Joe¨lle Benessiano, Jane-Lyse Samuel, Alain Tedgui
Journal: Circulation Research (1996)

Aortic fibronectin (FN) expression is augmented in hypertension. Increasing evidence suggests that both angiotensin II (Ang II) and mechanical factors may induce vascular remodeling in response to hypertension. We have previously shown that, in vitro, increased transmural pressure enhances FN expression in rabbit aortic media. To investigate the existence of a link between the effects of pressure and Ang II and to explore the mechanisms underlying such a relationship, we quantified the effect of Ang II and Ang II inhibitors on the pressure-dependent FN expression in a 3-day organ culture model of rabbit aorta using immunolabeling analysis and detected FN mRNAs by in situ hybridization. A dose-dependent effect of Ang II on FN expression was observed at both 80 and 150 mm Hg but not at 0 mm Hg (relaxed vessels). One μmol/L Ang II increased the media cross-sectional surface, showing FN expression from 7.9±0.7% (n=9) to 18.9±1.1% (n=4) at 80 mm Hg ( P &lt;.01) and from 17.4±1.8% (n=9) to 56.6%±3.6 (n=4) at 150 mm Hg ( P &lt;.001). In situ hybridization revealed that Ang II and pressure upregulated FN mRNA expression. Losartan, an AT 1 antagonist, not only blocked the Ang II effect but also inhibited the transmural pressure effect. Angiotensin-converting enzyme inhibition abolished the pressure-dependent FN expression and significantly diminished the effect of pressure in the presence of Ang II. The effect of renin-angiotensin system inhibitors was specific for FN, since neither bFGF nor laminin expression was affected by these agents. Taken together, the results demonstrate that (1) the effect of transmural pressure is mediated by the stimulation of a local renin-angiotensin system, resulting in a net Ang II production in the culture medium, (2) transmural pressure and Ang II act synergistically to enhance vascular FN expression, (3) AT 1 receptors mediate both the effects of pressure and of exogenous Ang II, and (4) the effect of Ang II on FN expression is regulated at a pretranslational level.
Transcription factor Runx2 controls the development and migration of plasmacytoid dendritic cells
Authors: Catherine M. Sawai, Vanja Sisirak, Hiyaa S. Ghosh, Esther Z. Hou, Michele Ceribelli, Louis M. Staudt, Boris Reizis
Journal: The Journal of Experimental Medicine (2013)

Plasmacytoid dendritic cells (pDCs) rapidly produce type I interferon (IFN-I) in response to viruses and are essential for antiviral immune responses. Although related to classical DCs (cDCs) in their development and expression profile, pDCs possess many distinct features. Unlike cDCs, pDCs develop in the bone marrow (BM) and emerge into peripheral lymphoid organs and tissues as fully differentiated cells. We now report that pDCs specifically express Runx2, a Runt family transcription factor that is essential for bone development. pDCs in Runx2-deficient mice developed normally in the BM but were greatly reduced in the periphery. The defect was cell-intrinsic and was associated with the retention of mature Ly49Q(+) pDCs in the BM. Runx2 was required for the expression of several pDC-enriched genes, including the chemokine receptors Ccr2 and Ccr5. Mature pDCs expressed high levels of Ccr5 at the cell surface, and Ccr5-deficient pDCs in a competitive setting were reduced in the periphery relative to the BM. Thus, Runx2 is required for the emergence of mature BM pDCs into the periphery, in a process that is partially dependent on Ccr5. These results establish Runx2 as a lineage-specific regulator of immune system development.
Atlas of Gastroenterology
Authors: S CAIRNS
Journal: Gut (2001)

index and I personally do not like the idea of paginating in sections and chapters.With a book of this length it is surely easier to simply number the pages.However, these are minor complaints and on the whole I would recommend this book to anyone interested in liver disease and particularly to trainees in gastroenterology, hepatology, or hepatobiliary surgery who will come back to this book again and again.