tbuckley/cabot-search huggingface dataset:
Epidemiology of asbestos-related diseases.
Authors: R A Lemen, J M Dement, J K Wagoner
Journal: Environmental Health Perspectives (1980)

This paper is intended to give the reader an overview of the epidemiology of asbestos-related diseases and is restricted to primarily occupational exposure studies. However, some mention of nonoccupational exposures are made because of their direct relationship to a worker or to a secondary occupational source. Over 100 epidemiological studies are reviewed, dating back to the first case of asbestos-associated disease reported by Montague Murray in 1906. The studies are divided by specific fiber type and by specific disease outcomes and the interaction of asbestos and cigarette smoking is discussed in great detail.
Maternally transmitted target antigen for unrestricted killing by NZB T lymphocytes.
Authors: K Fischer Lindahl, M Bocchieri, R Riblet
Journal: The Journal of Experimental Medicine (1980)

A new target antigen for unrestricted killing was defined by NZB T lymphocytes which were immunized and restimulated with H-2-identical BALB/c spleen cells. These effector cells killed nearly all target cells tested, irrespective of their H-2 type, but did not kill NZB target cells. The response was shown to have three major components: unrestricted killing specific for Qed-1b, H-2d-restricted killing specific for minor histocompatibility antigens, and unrestricted killing specific for a new antigen, Mta. Mta is present on normal and mitogen-stimulated T and B lymphocytes and on several tumor lines. It was found on cells from 26 mouse strains tested, including two substrains of NZB, representing 9 different H-2 types and 14 different non-H-2 backgrounds. Analysis of the NX8 recombinant inbred lines (derived from Mta-NZB/Icr and Mta+C58/J parents) suggested that Mta is maternally transmitted. This was confirmed by typing of reciprocal F1 hybrids and backcrosses between positive and negative strains: Mta+ females bear Mta+ offspring and Mta- females Mta- offspring, irrespective of the phenotype of the males.
–463 G/A myeloperoxidase promoter polymorphism in giant cell arteritis
Authors: C Salvarani, B Casali, E Farnetti, N Pipitone, D Nicoli, P L Macchioni, L Cimino, G L Bajocchi, M G Catanoso, L Pattacini, A Ghinoi, G Restuccia, L Boiardi
Journal: Annals of the Rheumatic Diseases (2007)

To investigate potential associations between-463 G/A myeloperoxidase (MPO) promoter polymorphism and susceptibility to, and clinical features of giant cell arteritis (GCA).A total of 156 patients with biopsy-proven GCA who were residents of Reggio Emilia, Italy, and 235 population-based controls from the same geographic area were genotyped for-463 G/A promoter polymorphism of the MPO gene by molecular methods. The patients were subgrouped according to the presence or absence of polymyalgia rheumatica and severe ischaemic complications (visual loss and/or cerebrovascular accidents).The distribution of the MPO-G/A genotype differed significantly between patients with GCA and the controls (p(corr) = 0.003). Allele G was significantly more frequent in patients with GCA than in the controls (p(corr) = 0.0002, OR 2.0, 95% CI 1.4 to 2.9). Homozygosity for the G allele was significantly more frequent in patients with GCA than in controls (p(corr) = 0.0002, OR 2.2, 95% CI 1.4 to 3.4). No significant associations were found when patients with GCA with and without polymyalgia rheumatica or with and without severe ischaemic complications were compared.Our findings show that the-463 G/A promoter polymorphism of the MPO gene is associated with GCA susceptibility and support a role for MPO in the pathophysiology of GCA.
Nebulised pentamidine as treatment for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome.
Authors: R F Miller, P Godfrey-Faussett, S J Semple
Journal: Thorax (1989)

Nebulised pentamidine as treatment for Pneumocystis carinu pneumonia in the acquired immunodeficiency syndrome SIR,-Dr Miller and his colleagues (July 1989;44:565-9) report that nebulised pentamidine when delivered by a Respirgard II nebuliser is more effective in the treatment of Pneumocystis carinii pneumonia than when delivered by an Acorn nebuliser.They state, however, that the mass median aerodynamic diameter (MMAD) of the aerosol produced by the Acorn is 2-6 pm.This means that 50% ofthe aerosol mass is contained in droplets ofless than 2-6 pm and 50% of the aerosol mass is contained in droplets of 2-6 pm or more.It is therefore a physical impossibility for 46% of the particles to be less than 3 9 pm, as the authors state.If this latter figure is correct, then the MMAD of the aerosol must be 3 9 pm or more.The correct size of the aerosol is critical to the interpretation of this study.Newman and colleagues have shown that the MMAD of the Acorn nebuliser, when measured in the same manner, ranges from 4 5 to 5-7 pm.'It seems likely that Dr Miller and his colleagues have miscalculated the MMAD.Only one patient from the group treated by Acorn nebulisers was seen to have oozing and contact bleeding at bronchoscopy, whereas four patients from the Respirgard group, which delivers a smaller droplet aerosol, were noted to have these findings.It is therefore difficult to implicate the pentamidine as the cause of these abnormalities, as the larger aerosol (delivered by the Acorn nebuliser) would be expected to produce a greater upper airway deposition, and so cause more rather than less mucosal irritation.Moreover, the authors state that the diagnosis of pneumocystis pneumonia was made by bronchoscopy before pentamidine was started (with the exception of one patient treated empirically).How is it then possible for the nebulised pentamidine to have caused the mucosal friability attributed to it?
Ensuring the Involvement of Children in the Evaluation of New Tuberculosis Treatment Regimens
Authors: William J Burman, Mark F Cotton, Diana M Gibb, A. Sarah Walker, Andrew A Vernon, Peter R Donald
Journal: PLoS Medicine (2008)

Children are a critical part of the global tuberculosis pandemic with an estimated 900000 cases and 100000 deaths per year. In high-burden settings children make up as much as 20% of incident cases of active tuberculosis. Furthermore young children have an increased risk of severe rapidly progressive forms of tuberculosis such as disseminated disease and meningitis. Therefore it is imperative that children benefit from improvements made in tuberculosis treatment. However children have only been included in one study of these new agents (a phase III trial of once-weekly rifapentine + isoniazid for latent tuberculosis). (excerpt)
Universes Collide: Combining Immunotherapy with Targeted Therapy for Cancer
Authors: Jennifer A. Wargo, Zachary A. Cooper, Keith T. Flaherty
Journal: Cancer Discovery (2014)

There have been significant advances in the past several years with regard to targeted therapy and immunotherapy for cancer. This is highlighted in melanoma, where treatment with targeted therapy (against the BRAF oncoprotein) results in responses in the majority of patients, although the duration of response is limited. In contrast, treatment with immunotherapy results in a lower response rate, but one that tends to be more durable. Insights about mechanisms of response and potential synergy between these treatment strategies for melanoma are a focus of this review, with opportunities to extend these insights to the treatment of other cancers.Two major advances in melanoma have occurred concurrently and involve treatment with targeted therapy and immune checkpoint blockade. However, each of these approaches has limitations with regard to overall response rates or duration of response. To address this, investigators have proposed combining these strategies, and this concept is being tested empirically in clinical trials. There is a scientific rationale supporting the combination of targeted therapy and immunotherapy, and these concepts are discussed herein.
Pathogenic role of angiotensin II and oxidised LDL in obstructive sleep apnoea
Authors: T. Kizawa, Y. Nakamura, S. Takahashi, S. Sakurai, K. Yamauchi, H. Inoue
Journal: European Respiratory Journal (2009)

A sustained elevation of oxidative stress in patients with obstructive sleep apnoea syndrome (OSAS) might help to explain their increased risk for cardiovascular diseases. We tested the hypothesis that the values of oxidative stress are increased in otherwise healthy subjects with OSAS when compared with closely matched control subjects. We performed a prospective study of 38 subjects who did not have OSAS and 37 patients with OSAS. Plasma indices of angiotensin (Ang) II, vascular endothelial growth factor (VEGF), oxidised low-density lipoprotein (oxLDL), and circulating endothelial precursor cells (CEPs) were measured in OSAS patients and in matched controls. Peripheral blood mononuclear cells (PBMCs) were obtained from both groups and co-cultured with endothelial cells to examine the effects on tube formation. The OSAS group showed increased levels of Ang II, VEGF, oxLDL and CEPs, which were decreased after nasal continuous positive airway pressure (nCPAP) treatment. In vitro, PBMCs from the OSAS group induced tube formation. Ang II, oxLDL, and Ang II-stimulated PBMCs induced lectin-like oxLDL receptor (LOX-1) expression and VEGF receptor-2 activation on endothelial cells, respectively. These observations suggest an important role of Ang II and oxLDL-mediated LOX-1 upregulation in endothelial cell injury in patients with OSAS.
Clinical Relevance of <i>HER2</i> Overexpression/Amplification in Patients With Small Tumor Size and Node-Negative Breast Cancer
Authors: Giuseppe Curigliano, Giuseppe Viale, Vincenzo Bagnardi, Luca Fumagalli, Marzia Locatelli, Nicole Rotmensz, Raffaella Ghisini, Marco Colleoni, Elisabetta Munzone, Paolo Veronesi, Stefano Zurrida, Franco Nolè, Aron Goldhirsch
Journal: Journal of Clinical Oncology (2009)

To assess the prognostic role of HER2 overexpression/amplification in patients with node-negative, pT1a-b breast cancers.All patients with HER2-positive breast cancer were identified among a population of 2,130 patients whose diseases were staged as pT1a-b, pN0 and who underwent surgery at the European Institute of Oncology from 1999 to 2006. A matched cohort was selected by using variables of hormone receptor status, age, and year of surgery. We estimated rates of local and distant recurrence, disease-free survival (DFS), and overall survival (OS) in the two groups.We identified 150 consecutive patients with pT1a-b, pN0, HER2-positive tumors. No patient received adjuvant trastuzumab. The median follow-up was 4.6 years (range, 1.0 to 9.0 years). In the hormone receptor-positive group, 5-year DFS rates were 99% (95% CI, 96% to 100%) for HER2-negative disease and 92% (95% CI, 86% to 99%) for HER2-positive disease. In the hormone receptor-negative group, 5-year DFS rates were 92% (95% CI, 84% to 100%) for HER2-negative disease and 91% (95% CI, 84% to 99%) for HER2-positive disease. Overall, the hazard ratio (HR) associated with HER2 overexpression was 2.4 (95% CI, 0.9 to 6.5; P = .09). After analysis was adjusted for pT1 stage, hormone receptor-positive disease with HER2-positive status was associated with a worse prognosis (HR, 5.1; 95% CI, 1.0 to 25.7). OS in HER2-positive, pT1a-b, pN0 breast cancer was similar irrespective of the hormone receptor status (P = .93).Patients with node-negative, HER2 positive, pT1a-b breast cancer have a low risk of recurrence at 5 years of follow-up. In patients with hormone receptor-positive disease and pT1a-b, N0 tumors, HER2 overexpression was associated with a worse DFS.
Biologically Inactive Leptin and Early-Onset Extreme Obesity
Authors: Martin Wabitsch, Jan-Bernd Funcke, Belinda Lennerz, Ursula Kuhnle-Krahl, Georgia Lahr, Klaus-Michael Debatin, Petra Vatter, Peter Gierschik, Barbara Moepps, Pamela Fischer-Posovszky
Journal: New England Journal of Medicine (2014)

Mutations in the gene encoding leptin (LEP) typically lead to an absence of circulating leptin and to extreme obesity. We describe a 2-year-old boy with early-onset extreme obesity due to a novel homozygous transversion (c.298G→T) in LEP, leading to a change from aspartic acid to tyrosine at amino acid position 100 (p.D100Y) and high immunoreactive levels of leptin. Overexpression studies confirmed that the mutant protein is secreted but neither binds to nor activates the leptin receptor. The mutant protein failed to reduce food intake and body weight in leptin-deficient ob/ob mice. Treatment of the patient with recombinant human leptin (metreleptin) rapidly normalized eating behavior and resulted in weight loss.
In Vivo Visualization of Cardiac Allograft Rejection and Trafficking Passenger Leukocytes Using Bioluminescence Imaging
Authors: Masashi Tanaka, Rutger-Jan Swijnenburg, Feny Gunawan, Yu-An Cao, Yang Yang, Anthony D. Caffarelli, Jorg L. de Bruin, Cristopher H. Contag, Robert C. Robbins
Journal: Circulation (2005)

Background— We investigated the feasibility of bioluminescence imaging (BLI) for the in vivo assessment of cardiac allograft viability and visualization of passenger leukocytes during the course of acute rejection. Methods and Results— Hearts of FVB (H-2 q ) luciferase-green fluorescent protein transgenic mice (β-actin promoter) or FVB luciferase transgenic mice (CD5 promoter) were heterotopically transplanted into either BALB/c (H-2 d ) or FVB recipients. Light intensity emitting from the recipient animals was measured daily by in vivo BLI until 12 days after transplantation. Graft beating score (0 to 4) was assessed by daily abdominal palpation until 12 days after transplantation. Inflammatory cell infiltration (CD45 stain) and structural changes of green fluorescent protein-positive cardiomyocytes were followed by immunohistochemistry. All cardiac allografts were acutely rejected by 12 days after transplantation. The intensity of light emitting from cardiac allografts declined 4 days after transplantation and correlated with graft beating scores ( R 2 =0.91, P =0.02). Immunohistochemistry confirmed these results by showing an increase of CD45 + inflammatory cell infiltration and destruction of green fluorescent protein-positive cardiomyocytes in the cardiac allografts during acute rejection. In vivo BLI visualized migration and proliferation of CD5 + passenger leukocytes in both syngeneic and allogeneic recipients. In the allograft recipients, light signal from CD5 + passenger leukocytes peaked at 6 hours and diminished by 12 hours, whereas in the syngeneic recipients, the signal remained high until 10 days after transplantation. Conclusions— BLI is a useful modality for the quantitative assessment of in vivo cardiac graft viability and tracking of passenger leukocytes in vivo during the course of acute rejection.
Functional Analysis of Alternative Isoforms of the Transcription Factor PAX3 in Melanocytes <i>In vitro</i>
Authors: Qiuyu Wang, Shant Kumar, Mark Slevin, Patricia Kumar
Journal: Cancer Research (2006)

Abstract Transcription factor PAX3 has seven isoforms of which PAX3c has been studied extensively whereas the functions of the other isoforms are less well known. Here, we found that PAX3 isoforms in a stable transfection system have different biological functions in mouse melanocytes in vitro. PAX3a and PAX3b had negative effects on melanocyte proliferation but had no discernable effect on melanocyte growth in soft agar. PAX3a did not affect cell migration and apoptosis but PAX3b reduced migration and accelerated apoptosis. PAX3c and PAX3d promoted cell proliferation, migration, transformation, and survival. PAX3e reduced melanocyte growth; transformation and migration were unchanged and apoptosis was increased in vitro. PAX3g did not influence cell proliferation or apoptosis. Cells expressing PAX3g were able to grow in soft agar but migration was reduced. PAX3h increased cell proliferation, migration, survival, and transformation. These functional studies have advanced our understanding of the effects of PAX3 isoforms in melanocytes and their potential contribution in tumorigenesis. (Cancer Res 2006; 66(17): 8574-80)
In vivo role of ER-associated peptidase activity in tailoring peptides for presentation by MHC class Ia and class Ib molecules
Authors: Jingbo Yan, Vrajesh V. Parekh, Yanice Mendez-Fernandez, Danyvid Olivares-Villagómez, Srdjan Dragovic, Timothy Hill, Derry C. Roopenian, Sebastian Joyce, Luc Van Kaer
Journal: The Journal of Experimental Medicine (2006)

Endoplasmic reticulum (ER)-associated aminopeptidase (ERAP)1 has been implicated in the final proteolytic processing of peptides presented by major histocompatibility complex (MHC) class I molecules. To evaluate the in vivo role of ERAP1, we have generated ERAP1-deficient mice. Cell surface expression of the class Ia molecules H-2Kb and H-2Db and of the class Ib molecule Qa-2 was significantly reduced in these animals. Although cells from mutant animals exhibited reduced capacity to present several self- and foreign antigens to Kb-, Db-, or Qa-1b–restricted CD8+ cytotoxic T cells, presentation of some antigens was unaffected or significantly enhanced. Consistent with these findings, mice generated defective CD8+ T cell responses against class I–presented antigens. These findings reveal an important in vivo role of ER-associated peptidase activity in tailoring peptides for presentation by MHC class Ia and class Ib molecules.
Topical Sodium Cromoglycate in Atopic Dermatitis A Disappointing but Informative Trial
Authors: N.‐I. M. Kjellman, I. M. Gustafsson
Journal: Allergy (1986)

Forty children with atopic eczema requiring topical steroids entered a double‐blind group comparative study over 12 weeks and were randomized to either 4% sodium cromoglycate (SCG) in an oil‐in‐water cream or matching placebo cream. The eczema was evaluated on area charts for 20 parts of the body at five clinic visits. In addition, the families kept diaries on symptoms and treatment. After 3 weeks there were small but statistically significant decreases in severity scores recorded at the clinical visits in the SCG group compared with small increases in the placebo group. However, there were no statistically significant differences in the diary card data during the first 3 weeks of treatment or in any other period, nor were significant differences found in any efficacy data collected during the other 9 weeks of the trial. There were no marked differences in treatment opinions, unusual symptoms, skin infections, use of topical steroids or drugs, or acceptability data between the groups. Staphylococcus aureus was found once or twice in cultures from eczema lesions in 31 of 40 children with no marked group difference. The trial showed that there is great need for improved information, family support and topical as well as general treatment in childhood atopic eczema, but topical SCG did not relieve the patients’eczema.
Whole-Genome Duplication and the Functional Diversification of Teleost Fish Hemoglobins
Authors: Juan C. Opazo, G. Tyler Butts, Mariana F. Nery, Jay F. Storz, Federico G. Hoffmann
Journal: Molecular Biology and Evolution (2012)

Subsequent to the two rounds of whole-genome duplication that occurred in the common ancestor of vertebrates, a third genome duplication occurred in the stem lineage of teleost fishes. This teleost-specific genome duplication (TGD) is thought to have provided genetic raw materials for the physiological, morphological, and behavioral diversification of this highly speciose group. The extreme physiological versatility of teleost fish is manifest in their diversity of blood-gas transport traits, which reflects the myriad solutions that have evolved to maintain tissue O(2) delivery in the face of changing metabolic demands and environmental O(2) availability during different ontogenetic stages. During the course of development, regulatory changes in blood-O(2) transport are mediated by the expression of multiple, functionally distinct hemoglobin (Hb) isoforms that meet the particular O(2)-transport challenges encountered by the developing embryo or fetus (in viviparous or oviparous species) and in free-swimming larvae and adults. The main objective of the present study was to assess the relative contributions of whole-genome duplication, large-scale segmental duplication, and small-scale gene duplication in producing the extraordinary functional diversity of teleost Hbs. To accomplish this, we integrated phylogenetic reconstructions with analyses of conserved synteny to characterize the genomic organization and evolutionary history of the globin gene clusters of teleosts. These results were then integrated with available experimental data on functional properties and developmental patterns of stage-specific gene expression. Our results indicate that multiple α- and β-globin genes were present in the common ancestor of gars (order Lepisoteiformes) and teleosts. The comparative genomic analysis revealed that teleosts possess a dual set of TGD-derived globin gene clusters, each of which has undergone lineage-specific changes in gene content via repeated duplication and deletion events. Phylogenetic reconstructions revealed that paralogous genes convergently evolved similar functional properties in different teleost lineages. Consistent with other recent studies of globin gene family evolution in vertebrates, our results revealed evidence for repeated evolutionary transitions in the developmental regulation of Hb synthesis.
Synthesis of interleukin-1? in primary biliary cirrhosis: Relationship to treatment with methotrexate or colchicine and disease progression*1
Authors: L MILLER
Journal: Hepatology (1995)

Primary biliary cirrhosis (PBC) is a chronic, progressive, cholestatic liver disease. Interleukin-1β (IL-1β) may play a role in the pathogenesis of PBC by contributing to altered immune function and fibrosis. Colchicine or methotrexate has some beneficial effects in the treatment of PBC, and also affects interleukin-1 (IL-1β). Therefore, we prospectively studied the synthesis of IL-1β by peripheral blood mononuclear cells (PBMC) from 42 patients with PBC entered into a randomized, double-blind, double-dummy controlled trial of colchicine and methotrexate. PBMC obtained at entry, 6, 12, 18, and 24 months were stimulated to produce IL-1β with phytohemagglutinin (PHA), lipopolysaccharide (LPS), Staphylococcus epidermidis, recombinant IL-2, or mitochondrial antigen. Patients in the two treatment groups did not differ at entry in biochemical measures or liver histological stage. Over 24 months in both groups, serum bilirubin and histologic stage remained stable and alkaline phosphatase decreased significantly. For all patients, synthesis of IL-1β increased constitutively and in response to immune-mediated stimulants (PHA, IL-2, and mitochondrial antigen) but not the bacterial stimulants LPS or S epidermidis. Compared with levels of IL-1β at entry, PHA induced increases for patients treated with methotrexate (12, 18, and 24 months) or colchicine (18 and 24 months). At 24 months, IL-2-induced IL-1β synthesis was increased in patients treated with methotrexate, whereas S epidermidis-induced IL-1β was enhanced in colchicine-treated patients. Before treatment, IL-1β production did not relate to severity of disease except in response to S epidermidis. Notably, in patients with stable or improving liver histological stage, IL-1β synthesis increased dramatically at 12 months in response to IL-2 and S epidermidis, and also to LPS by 24 months. Alterations in IL-1β synthesis in patients with PBC may reflect underlying immunoregulatory changes that contribute to disease progression or stabilization.