tbuckley/cabot-search huggingface dataset:
Chemokine (C‐X‐C motif) receptor 3–positive B cells link interleukin‐17 inflammation to protumorigenic macrophage polarization in human hepatocellular carcinoma
Authors: Rui‐Xian Liu, Yuan Wei, Qiu‐Hui Zeng, Ka‐Wo Chan, Xiao Xiao, Xiao‐Yu Zhao, Min‐Min Chen, Fang‐Zhu Ouyang, Dong‐Ping Chen, Limin Zheng, Xiang‐Ming Lao, Dong‐Ming Kuang
Journal: Hepatology (2015)

B cells consistently represent abundant cellular components in tumors; however, direct evidence supporting a role for B cells in the immunopathogenesis of human cancers is lacking, as is specific knowledge of their trafficking mechanisms. Here, we demonstrate that chemokine (C‐X‐C motif) receptor 3–positive (CXCR3 + ) B cells constitute approximately 45% of B‐cell infiltrate in human hepatocellular carcinoma (HCC) and that their levels are positively correlated with early recurrence of HCC. These cells selectively accumulate at the invading edge of HCC and undergo further somatic hypermutation and immunoglobulin G–secreting plasma cell differentiation. Proinflammatory interleukin‐17 + cells are important for the induction of epithelial cell–derived CXCR3 ligands CXCL9, CXCL10, and CXCL11, which subsequently promote the sequential recruitment and further maturation of CXCR3 + B cells. More importantly, we provide evidence that CXCR3 + B cells, but not their CXCR3 – counterparts, may operate in immunoglobulin G–dependent pathways to induce M2b macrophage polarization in human HCC. Depletion of B cells significantly suppresses M2b polarization and the protumorigenic activity of tumor‐associated macrophages and restores the production of antitumorigenic interleukin‐12 by those cells in vivo . Conclusion : Selective recruitment of CXCR3 + B cells bridges proinflammatory interleukin‐17 response and protumorigenic macrophage polarization in the tumor milieu, and blocking CXCR3 + B‐cell migration or function may help defeat HCC.(H epatology 2015;62:1779–1790)
A physician objects
Authors: C. Booth
Journal: Journal of the Royal Society of Medicine (2004)

In his review of my book of essays A Physician Reflects (January 2004 JRSM), Adrian Marston states that I have made a valiant attempt to credit the `denizens of Regents Park' (i.e. the Royal College of Physicians) with the discovery of the cause of lung cancer. I made no such attempt. The College, it should be emphasized, never discovered anything. Not even the most prejudiced Fellow of the College would make such an assertion, let alone a serious student of the history of 20th century medicine. Your reviewer suggests that I will cause `much innocent merriment among surgeons and others'. The College has paid tribute to the outstanding work of Sir Austin Bradford Hill and Sir Richard Doll on a number of occasions. Furthermore, Sir Austin was the first non-medical scientist to be elected to the Fellowship of the College, nominated by Sir Harold Himsworth, Secretary of the Medical Research Council, which gave strong support to the work of Bradford Hill and Doll. Your reviewer's remarks will cause more sadness than merriment among those serious historians who were kind enough to read the essays before publication.
Two cases of pregnancy with coarctation of the aorta
Authors: S. Venning, L. J Freeman, K. Stanley
Journal: Journal of the Royal Society of Medicine (2003)

An increasing number of women with previously repaired coarctation of the aorta are now becoming pregnant; uncorrected coarctation may also present for the first time in pregnancy with hypertension. There are vital issues pertaining to maternal risk and management.
Increased incidence of TB disease within the health-care workers in an intermediate TB burden country
Authors: Hsi Chu, Yung-Tai Chen
Journal: European Respiratory Journal (2014)

Objectives  To determine the association between tuberculosis risk and health-care worker.   Design, setting and patients:  The health-care worker were retrieved from the Taiwan NationalHealth Insurance Database from 2000 to 2010. Among health-care worker at the cohort entry, controls were matched with age, gender, risk factor for tuberculosis on a 1:1 ratio.   Main outcome and Measures:  All subjects were followed up from the date of enrollment until tuberculosis occurrence, death, or December 31, 2010.   Results:  There were 11,811 health-care worker and 11,811 matched controls enrolled. Among these subjects, 62 health-care workers and 38 matched controls developed tuberculosis during a median follow-up period of 9.4 years. Health-care worker had a higher incidence of tuberculosis compared with controls (61.08 versus 37.81 per 100,000 person-years) and a greater risk of overall tuberculosis (adjusted hazard ratio[AHR] 1.62, 95% confidence interval [CI], 1.08-2.43), mainly located at pulmonary (AHR 1.56, 95% CI, 1.02-2.39) instead of extra-pulmonary.   Conclusion and Relevance:  Health-care worker is independently associated with higher risk of subsequent tuberculosis. Health-care worker should pay attention to awareness and modification of the risks for tuberculosis.
The Adult Respiratory Distress Syndrome Cognitive Outcomes Study
Authors: Mark E. Mikkelsen, Jason D. Christie, Paul N. Lanken, Rosette C. Biester, B. Taylor Thompson, Scarlett L. Bellamy, A. Russell Localio, Ejigayehu Demissie, Ramona O. Hopkins, Derek C. Angus
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Cognitive and psychiatric morbidity is common and potentially modifiable after acute lung injury (ALI). However, practical measures of neuropsychological function for use in multicenter trials are lacking.
The C-C chemokine receptors CCR4 and CCR8 identify airway T cells of allergen-challenged atopic asthmatics
Authors: Paola Panina-Bordignon, Alberto Papi, Margherita Mariani, Pietro Di Lucia, Gianluca Casoni, Cinzia Bellettato, Cecilia Buonsanti, Deborah Miotto, Cristina Mapp, Antonello Villa, Gianluigi Arrigoni, Leonardo M. Fabbri, Francesco Sinigaglia
Journal: Journal of Clinical Investigation (2001)

In vitro polarized human Th2 cells preferentially express the chemokine receptors CCR3, CCR4, and CCR8 and migrate to their ligands: eotaxin, monocyte-derived chemokine (MDC), thymus- and activation-regulated chemokine (TARC), and I-309. We have studied the expression of chemokines and chemokine receptors in the airway mucosa of atopic asthmatics. Immunofluorescent analysis of endobronchial biopsies from six asthmatics, taken 24 hours after allergen challenge, demonstrates that virtually all T cells express IL-4 and CCR4. CCR8 is coexpressed with CCR4 on 28% of the T cells, while CCR3 is expressed on eosinophils but not on T cells. Expression of the CCR4-specific ligands MDC and TARC is strongly upregulated on airway epithelial cells upon allergen challenge, suggesting an involvement of this receptor/ligand axis in the regulation of lymphocyte recruitment into the asthmatic bronchi. In contrast to asthma, T cells infiltrating the airways of patients with chronic obstructive pulmonary disease and pulmonary sarcoidosis produce IFN-γ and express high levels of CXCR3, while lacking CCR4 and CCR8 expression. These data support the role of CCR4, of its ligands MDC and TARC, and of CCR8 in the pathogenesis of allergen-induced late asthmatic responses and suggest that these molecules could be considered as targets for therapeutic intervention.
Selenium Accumulation in Prostate Tissue During a Randomized, Controlled Short-term Trial of <i>l</i>-Selenomethionine: a Southwest Oncology Group Study
Authors: Anita L. Sabichi, J. Jack Lee, Robert J. Taylor, Ian M. Thompson, Brian J. Miles, Catherine M. Tangen, Lori M. Minasian, Louis L. Pisters, John R. Caton, Joseph W. Basler, Seth P. Lerner, David G. Menter, James R. Marshall, E. David Crawford, Scott M. Lippman
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Epidemiologic and clinical data suggest that selenium could prevent prostate cancer, but it has not been shown that supplemental selenium leads to an increased concentration of selenium in prostate tissue compared with adjacent tissue. Experimental Design: We conducted a randomized, controlled, short-term trial of l-selenomethionine (SeMet) versus observation in men with organ-confined prostate cancer. The primary endpoint was the measurement of selenium concentration in prostate tissue and seminal vesicle (SV). We assessed baseline selenium levels in serum and in toenail specimens (reflecting long-term intake) and post-intervention selenium levels in serum, and in prostate and SV tissues using hydride generation atomic fluorescence spectroscopy. Results: Sixty-six eligible patients were randomly assigned to the SeMet (n = 34) or observation (n = 32) arm; both arms had similar baseline patient characteristics. Baseline serum selenium was similar in the two groups (P = 0.64). Baseline toenail selenium levels were slightly higher in the SeMet group than in the control group (P = 0.07). After the intervention, the mean serum selenium level increased 15% in the SeMet arm and was higher than in the observation arm (P = 0.001). The selenium concentration in prostate tissue was 22% higher in the SeMet arm (n = 26) than in the observation arm (n = 25; 1.80 versus 1.47 ppm; P = 0.003, Wilcoxon rank sum test) and remained significantly higher after adjusting for chronic selenium intake (P = 0.021, ANCOVA). SV selenium concentration was similar in both groups (P = 0.384) and was lower than in prostate tissue. Conclusions: The present study is the first to show that selenium taken as oral supplementation accumulates preferentially in the human prostate gland as opposed to the SV. These findings support the hypothesis that oral selenium supplementation may contribute to the cancer preventive effects of selenium.
Active Surveillance for Prostate Cancer: Progress and Promise
Authors: Matthew R. Cooperberg, Peter R. Carroll, Laurence Klotz
Journal: Journal of Clinical Oncology (2011)

Widespread prostate-specific antigen (PSA) –based screening and aggressive treatment of prostate cancer have reduced mortality rates substantially, but both remain controversial in large part because of high rates of overdiagnosis and overtreatment of otherwise indolent tumors. Active surveillance—or close monitoring of PSA levels combined with periodic imaging and repeat biopsies—is gaining acceptance as an alternative initial management strategy for men with low-risk prostate cancer. In reported series, rates of progression to active treatment with intermediate-term follow-up have ranged from 14% to 41%, and likelihood of subsequent cure with surgery or radiation does not seem to be compromised by an initial trial of surveillance. Two related challenges to broader acceptance of surveillance are better characterization at time of diagnosis of the risk of progression (including likelihood that given tumor may have been undersampled by diagnostic biopsy) and validation of optimal end points once surveillance begins. Both are subjects of intense ongoing investigation, with emerging biomarkers and novel imaging tests expected to facilitate decision making substantially. Recent reports have suggested active surveillance can be a cost-effective approach and preserve quality of life, but these questions must be assessed more definitively in prospective cohorts. Ultimately, by minimizing the harms of overtreating low-risk prostate cancer, active surveillance may help settle the controversy surrounding prostate cancer screening and management.
Bacterial CpG-DNA Aggravates Immune Complex Glomerulonephritis
Authors: Hans-Joachim Anders, Bernhard Banas, Yvonne Linde, Lars Weller, Clemens D. Cohen, Matthias Kretzler, Stefan Martin, Volker Vielhauer, Detlef Schlöndorff, Hermann-Josef Gröne
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Immune complex glomerulonephritis (GN) often deteriorates during infection with viruses and bacteria that, in contrast to mammals, have DNA that contains many unmethylated CpG motifs. Balb/c mice with horse apoferritin-induced GN (HAF-GN) were treated with either saline, CpG-oligodeoxynucleotides (ODN), or control GpC-ODN. Only CpG-ODN exacerbated HAF-GN with an increase of glomerular macrophages, which was associated with massive albuminuria and increased renal MCP-1/CCL2, RANTES/CCL5, CCR1, CCR2, and CCR5 mRNA expression. CpG-ODN induced a Th1 response as indicated by serum anti-HAF IgG2a titers, mesangial IgG2a deposits, and splenocyte IFN-γ secretion. Messenger RNA for the CpG-DNA receptor Toll-like reeptor 9 (TLR9) was present in kidneys with HAF-GN but not in normal kidneys. The source of TLR9 mRNA in HAF-GN could be infiltrating macrophages or intrinsic renal cells, e.g., mesangial cells; but, in vitro, only murine J774 macrophages expressed TLR9. In J774 cells, CpG-ODN induced the chemokines MCP-1/CCL2 and RANTES/CCL5 and the chemokine receptors CCR1 and CCR5. It is concluded that CpG-DNA can aggravate preexisting GN via a shift toward a Th1 response but also by a novel pathway involving TLR9-mediated chemokine and chemokine receptor expression by macrophages, which may contribute to the enhanced glomerular macrophage recruitment and activation. This mechanism may be relevant during infection-triggered exacerbation of human immune-complex GN and other immune-mediated diseases in general. E-mail: [email protected]
T-helper cell type-1 transcription factor T-bet is upregulated in pulmonary sarcoidosis
Authors: E. Kriegova, R. Fillerova, T. Tomankova, B. Hutyrova, F. Mrazek, T. Tichy, V. Kolek, R.M. du Bois, M. Petrek
Journal: European Respiratory Journal (2011)

Upregulation of genes for interferon (IFN)-γ and CXC chemokine receptor (CXCR)3 expression, two crucial molecules in sarcoid inflammation and granuloma formation, is directly controlled by the T-helper (Th)1 transcription factor T-bet (T-box, expressed in T-cells). However, there is no information on T-bet expression in sarcoidosis or its relationship with “sarcoidosis-associated” genes. Therefore, we investigated expression of T-bet mRNA and, in parallel, a spectrum of genes known to be involved in sarcoidosis pathogenesis. Transcripts were determined in bronchoalveolar lavage (BAL) cells from 62 sarcoidosis patients and 25 controls by quantitative RT-PCR; T-bet protein was localised by immunohistochemistry. Patient’s BAL cells expressed higher mRNA T-bet levels than those of controls (mean± sd fold change 3.64±1.72; p=0.00006). T-bet mRNA expression did not vary between clinical phenotypes as assessed by chest radiography stage, presence/absence of Löfgren's syndrome, extrapulmonary/pulmonary involvement or progressing/remitting disease (p&gt;0.05). T-bet mRNA expression correlated with expression of IFN-γ, CC chemokine ligand 5, CXC chemokine ligand (CXC)10, interleukin (IL)-2 receptor/IL-15 receptor β, CXCR3 and CXCR6 (p&lt;0.01). T-bet protein was localised to alveolar macrophages and lymphocytes, tissue multinucleated giant cells, macrophages and lymphocytes. In pulmonary sarcoidosis, T-bet upregulation is associated with changes in expression of IFN-γ, CXCR3 and chemokines/receptors involved in the pathogenesis of sarcoidosis, which suggests a role for T-bet in this Th1 disease, including modulation of some sarcoidosis-associated genes.
Neotendon formation induced by manipulation of the Smad8 signalling pathway in mesenchymal stem cells
Authors: A. Hoffmann
Journal: Journal of Clinical Investigation (2006)

Tissue regeneration requires the recruitment of adult stem cells and their differentiation into mature committed cells. In this study we describe what we believe to be a novel approach for tendon regeneration based on a specific signalling molecule, Smad8, which mediates the differentiation of mesenchymal stem cells (MSCs) into tendon-like cells. A biologically active Smad8 variant was transfected into an MSC line that coexpressed the osteogenic gene bone morphogenetic protein 2 (BMP2). The engineered cells demonstrated the morphological characteristics and gene expression profile of tendon cells both in vitro and in vivo. In addition, following implantation in an Achilles tendon partial defect, the engineered cells were capable of inducing tendon regeneration demonstrated by double quantum filtered MRI. The results indicate what we believe to be a novel mechanism in which Smad8 inhibits the osteogenic pathway in MSCs known to be induced by BMP2 while promoting tendon differentiation. These findings may have considerable importance for the therapeutic replacement of tendons or ligaments and for engineering other tissues in which BMP plays a pivotal developmental role.
Prognostic value of the type of onset of rheumatoid arthritis.
Authors: R Luukkainen, H Isomaki, A Kajander
Journal: Annals of the Rheumatic Diseases (1983)

The type of onset in 235 patients with rheumatoid arthritis (RA) was acute in 69, subacute in 55, and gradual in 111 patients. The radiological destruction of the hands and feet after 7 years from the beginning of the disease was the same in all patient groups. Thus the nature of the onset of RA seems not to have any significant influence on the outcome of the arthritis.
John Hunter Annan
Authors: H M. Williams
Journal: BMJ (2005)

Former consultant orthopaedic surgeon Huddersfield Royal Infirmary (b 1915; q Edinburgh 1938; FRCS Ed), d 24 January 2004.

Hunter Annan joined the Royal Army Medical Corps in 1940. He was taken prisoner of war, and later transferred to a PoW hospital, becoming medical officer to the British and American section. Although inexperienced he carried out many operations over the next two years. He was mentioned in dispatches three times. In 1954 he was appointed consultant orthopaedic surgeon at Huddersfield Royal Infirmary, retiring in 1980. His special interests were paediatric orthopaedics and leg equalisation. He leaves a wife, Muriel; three children; and seven grandchildren.
Hypertension in mice lacking 11β-hydroxysteroid dehydrogenase type 2
Authors: Yuri Kotelevtsev, Roger W. Brown, Stewart Fleming, Christopher Kenyon, Christopher R.W. Edwards, Jonathan R. Seckl, John J. Mullins
Journal: Journal of Clinical Investigation (1999)

Deficiency of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) in humans leads to the syndrome of apparent mineralocorticoid excess (SAME), in which cortisol illicitly occupies mineralocorticoid receptors, causing sodium retention, hypokalemia, and hypertension. However, the disorder is usually incompletely corrected by suppression of cortisol, suggesting additional and irreversible changes, perhaps in the kidney. To examine this further, we produced mice with targeted disruption of the 11β-HSD2 gene. Homozygous mutant mice (11β-HSD2–/–) appear normal at birth, but ∼50% show motor weakness and die within 48 hours. Both male and female survivors are fertile but exhibit hypokalemia, hypotonic polyuria, and apparent mineralocorticoid activity of corticosterone. Young adult 11β-HSD2–/– mice are markedly hypertensive, with a mean arterial blood pressure of 146 ± 2 mmHg, compared with 121 ± 2 mmHg in wild-type controls and 114 ± 4 mmHg in heterozygotes. The epithelium of the distal tubule of the nephron shows striking hypertrophy and hyperplasia. These histological changes do not readily reverse with mineralocorticoid receptor antagonism in adulthood. Thus, 11β-HSD2–/– mice demonstrate the major features of SAME, providing a unique rodent model to study the molecular mechanisms of kidney resetting leading to hypertension.
Targeted inactivation of the COP9 signalosome impairs multiple stagesof T cell development
Authors: Martina Panattoni, Francesca Sanvito, Veronica Basso, Claudio Doglioni, Giulia Casorati, Eugenio Montini, Jeffrey R. Bender, Anna Mondino, Ruggero Pardi
Journal: The Journal of Experimental Medicine (2008)

Genetic programs promoting cell cycle progression, DNA repair, and survival are coordinately induced in developing T cells and require rapid turnover of effector molecules. As the COP9 signalosome (CSN) has been placed at the crossroads of these programs in lower organisms, we addressed its role by conditionally deleting CSN5/JAB1, its catalytic subunit, in developing thymocytes. CSN5/JAB1(del/del) thymocytes show defective S phase progression and massive apoptosis at the double-negative (DN) 4-double-positive (DP) transition stage, which is paralleled by altered turnover of selected CSN-controlled substrates, including p53, IkappaB-alpha, and beta-catenin. Combined dysregulation of the p53 and NF-kappaB pathways affects thymocyte survival by altering the mRNA and protein levels of selected Bcl-2 family members. Genetic complementation analysis performed on p53(-/-), Bcl-xL/Bcl-2A1, or T cell receptor transgenic backgrounds indicates that CSN5/JAB1 acts at distinct developmental stages to coordinate proliferation, survival, and positive selection of thymocytes by controlling the induction of defined genetic programs acting downstream of CSN-regulated transcription factors.
MicroRNA-98 and microRNA-214 post-transcriptionally regulate enhancer of zeste homolog 2 and inhibit migration and invasion in human esophageal squamous cell carcinoma
Authors: Sheng-Dong Huang, Yang Yuan, Chong-Wen Zhuang, Bai-Ling Li, De-Jun Gong, Shu-Gang Wang, Zhi-Yong Zeng, He-Zhong Cheng
Journal: Molecular Cancer (2012)

Abstract Background The enhancer of zeste homolog 2 (EZH2) was found to be overexpressed and associated with tumor metastasis in esophageal squamous cell carcinoma (ESCC). On the other hand, it was reported that miR-26a, miR-98, miR-101, miR-124, miR-138 and miR-214 could inhibit the expression of EZH2 in some tumors. However, the role of miRNAs in the regulation of EZH2 expression in human ESCC has not been documented. The aim of this study was to determine the role of these miRNAs in the regulation of tumor metastasis via EZH2 overexpression in human ESCC. Methods and results The expression of these miRNAs and EZH2 mRNA were examined by qPCR and the expression of EZH2 protein was detected by western blot. The role of these miRNAs in migration and invasion was studied in ESCC cell line (Eca109) transfected with miRNA mimics or cotransfected with miRNA mimics and pcDNA-EZH2 plasmid (without the 3’-UTR of EZH2). Through clinical investigation, we found that miR-98 and miR-214 expression was significantly lower in ESCC tissues than in matched normal tissues, and the expression level of miR-98 and miR-214 was inversely correlated to EZH2 protein expression and the clinical features such as pathological grade, tumor stage and lymph node metastasis in ESCC. In Eca109 cells, overexpression of miR-98 and miR-214 significantly inhibited the migration and invasion of ESCC cells, which was reversed by transfection of EZH2. Conclusions These findings suggest that decreased expression of miR-98 and miR-214 might promote metastasis of human ESCC by inducing accumulation of EZH2 protein.