tbuckley/cabot-search huggingface dataset:
Association of Elevations of Specific T Cell and Monocyte Subpopulations in Rheumatoid Arthritis With Subclinical Coronary Artery Atherosclerosis
Authors: Robert Winchester, Jon T. Giles, Simona Nativ, Kendall Downer, Hui‐Zhu Zhang, Ayse Bag‐Ozbek, Afshin Zartoshti, Sabahat Bokhari, Joan M. Bathon
Journal: Arthritis & Rheumatology (2015)

Objective Coronary artery disease (CAD) is the leading cause of excess deaths in rheumatoid arthritis (RA). However, identification of features denoting patients with a risk of developing CAD is lacking. The composition of circulating peripheral blood mononuclear cell (PBMC) subsets in RA patients differs markedly from that in healthy controls with regard to the extent of T cell activation, with clonal expansion and differentiation to effector memory status, and presence of inflammatory monocytes. In this study, we sought to evaluate whether elevations in these PBMC subpopulations in RA patients could denote those with an increased risk of subclinical CAD, as determined by the presence of coronary artery calcification (CAC). Methods The study cohort comprised 72 patients with RA who underwent cardiac computed tomography to assess CAC. PBMC subsets were determined by multiparameter flow cytometry. Multivariable logistic regression was used to determine the associations between PBMC subpopulations and the presence of CAC. Results Among the 72 patients with RA, 33% had CAC and exhibited significant increases in the levels of circulating CD4 T cell subsets denoting activation and differentiation to the effector memory phenotypes. Analogous increases in the levels of CD8 T cell subsets, as well as in the CD14 high CD16+ intermediate monocyte subset, were also present in these patients, as compared to those without CAC. The increases in the CD4 and CD8 T cell subsets were highly intercorrelated, whereas the increases in CD14 high CD16+ monocytes were independent of elevations in the CD4 T cell subsets. After adjustments for relevant confounders, the levels of CD4+CD56+CD57+ T cells and CD14 high CD16+ monocytes remained associated with the presence of CAC. Conclusion These findings indicate that PBMC subsets are markers for the presence of CAC and suggest that mechanisms of atherogenesis in RA may operate in part through the elevations in these subsets, raising further questions about the mechanisms underlying the presence of such alterations in cell composition in patients with RA and the potential for shared etiologic pathways between RA and cardiovascular disease.
P3-07-20: An Independent Assessment of Seven Nomograms for Predicting the Probability of Additional Axillary Nodal Metastasis after Positive Sentinel Lymph Node Biopsy in a Cohort of British Breast Cancer Population.
Authors: RM Nadeem, LD Gudur, ZA Saidan
Journal: Cancer Research (2011)

Abstract Background Axillary lymph node dissection (ALND) is currently the recommended procedure in patients with positive sentinel lymph node (SLN) biopsy. A significant proportion of patients with positive SLNs will not have any additional metastasis in non-sentinel lymph nodes (NSLNs). Nomograms could identify a subgroup of patients with low risk of further disease in whom completion ALND can be avoided. The aim of this study is to assess the accuracy of currently available seven nomograms in a cohort of British breast cancer population. Methods: 138 patients with positive SLNs who underwent completion ALND between October 2006-April 2011 were identified. Multiple pathological variables including the histological size of the SLNs metastasis were analysed. Data was then used to calculate the probability of further metastasis in non-SLNs according to the seven nomograms that are currently in use: MSKCC, Cambridge, Turkish, Stanford, MDACC, Tenon and MOU models. The area under the receiver-operator characteristic (ROC) curve (AUC), 95% confidence intervals, false negative and positive rate were calculated for each nomogram. Subgroup analysis includes pathological tumour size (≤ 2 cm and &amp;gt;2 cm) and macro- or micrometastasis in SLNs. AUC value ≥ 0.80 has an excellent discriminative power. Results: 56 of 138 patients (41%) had additional metastasis in non-SLNs. AUC values with 95% confidence intervals and false negative rate are shown in table 1. 46/138(33.3%) had tumour size ≤ 2cm and 18/46( 39 %) had additional NSLNs metastasis. AUC values for the subgroups are shown in table 2. 19/138(14%) who had micrometastasis in SLNs, additional non-SLNs metastasis was seen in only one patient and AUC values were imprecise. Subgroup analysis identified 6 patients with micrometastasis and tumour size ≤ 2 cm, none had additional NSLNs metastasis so AUC values cannot be computed. 19/138(14%) who had extracapsular extension, additional non-SLNs metastasis was seen in 12/19(63%). Conclusion: MOU nomogram was more predictive than the other nomograms with a better AUC value and false negative rate. Subgroup analysis also shows persistently better AUC value for MOU nomogram. None of the models were able to achieve an AUC value ≥ 0.80 in a cohort of British breast cancer patients. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-20.
Effects of high dose intravenous immunoglobulin in two severe corticosteroid insensitive asthmatic patients
Authors: B. Vrugt, S. Wilson, E. van Velzen, A. Bron, J. K. Shute, S. T. Holgate, R. Djukanovic, R. Aalbers
Journal: Thorax (1997)

Preliminary observations of the clinical efficacy of intravenous immunoglobulin in two patients with severe corticosteroid insensitive asthma are reported. In both patients treatment with intravenous immunoglobulin resulted in clinical improvement and enabled a significant reduction in the dose of prednisolone. In one of the patients fibreoptic bronchoscopy with endobronchial biopsies was performed and peripheral blood was analysed by flow cytometry before and after treatment. Immunohistological analysis of the biopsy samples after treatment showed a decrease in the number of all cell types, especially CD3+ T cells, CD4+ T cells, and activated CD25+ T lymphocytes, which was associated with a reduction in peripheral blood T cell activation. Intravenous immunoglobulin may be a valid option for the treatment of corticosteroid insensitive asthma. To elucidate the role and mode of action of intravenous immunoglobulin further studies in larger groups of patients are needed.
Diversification of NRT2 and the Origin of Its Fungal Homolog
Authors: Jason C. Slot, Kelly N. Hallstrom, Patrick B. Matheny, David S. Hibbett
Journal: Molecular Biology and Evolution (2007)

We investigated the origin and diversification of the high-affinity nitrate transporter NRT2 in fungi and other eukaryotes using Bayesian and maximum parsimony methods. To assess the higher-level relationships and origins of NRT2 in eukaryotes, we analyzed 200 amino acid sequences from the Nitrate/Nitrite Porter (NNP) Family (to which NRT2 belongs), including 55 fungal, 41 viridiplantae (green plants), 11 heterokonts (stramenopiles), and 87 bacterial sequences. To assess evolution of NRT2 within fungi and other eukaryotes, we analyzed 116 amino acid sequences of NRT2 from 58 fungi, 40 viridiplantae (green plants), 1 rhodophyte, and 5 heterokonts, rooted with 12 bacterial sequences. Our results support a single origin of eukaryotic NRT2 from 1 of several clades of mostly proteobacterial NNP transporters. The phylogeny of bacterial NNP transporters does not directly correspond with bacterial taxonomy, apparently due to ancient duplications and/or horizontal gene transfer events. The distribution of NRT2 in the eukaryotes is patchy, but the NRT2 phylogeny nonetheless supports the monophyly of major groups such as viridiplantae, flowering plants, monocots, and eudicots, as well as fungi, ascomycetes, basidiomycetes, and agaric mushrooms. At least 1 secondary origin of eukaryotic NRT2 via horizontal transfer to the fungi is suggested, possibly from a heterokont donor. Our analyses also suggest that there has been a horizontal transfer of nrt2 from a basidiomycete fungus to an ascomycete fungus and reveal a duplication of nrt2 in the ectomycorrhizal mushroom genus, Hebeloma.
Non-Hodgkin Lymphoma in Jamaica and its Relation to Adult T-Cell Leukemia-Lymphoma
Authors: WILLIAM N. GIBBS
Journal: Annals of Internal Medicine (1987)

Of 95 patients consecutively diagnosed with non-Hodgkin lymphoma, 52 (55%) had antibodies to human T-cell leukemia-lymphoma virus, type I. Antibody positivity was strongly associated with skin involvement, leukemia, and hypercalcemia (p < 0.02). Two patients had systemic opportunistic infections. Neither meningeal nor lung infiltration was detected, and lymph node infiltration was diffuse in all patients. Of 36 patients who received immunophenotypic classifications, 30 had diseases that affected the T-cell system, and the cells of all tested patients with these diseases showed the helper/inducer (T4) phenotype. Twenty-seven of these thirty-six patients were found to have adult T-cell leukemia-lymphoma, and of the 27, 24 had antibodies to HTLV-I. The median duration of survival in patients with adult T-cell leukemia-lymphoma was 17 weeks, but a subgroup of 9 patients had indolent courses and a median survival of 81 weeks, which suggests that the disease has differing expression with courses that range from smoldering and indolent to acute and rapidly fatal. Hypercalcemia was the most important prognostic determinant of adult T-cell leukemia-lymphoma.
Circumventing Cancer Drug Resistance in the Era of Personalized Medicine
Authors: Levi A. Garraway, Pasi A. Jänne
Journal: Cancer Discovery (2012)

Abstract All successful cancer therapies are limited by the development of drug resistance. The increase in the understanding of the molecular and biochemical bases of drug efficacy has also facilitated studies elucidating the mechanism(s) of drug resistance. Experimental approaches that can help predict the eventual clinical drug resistance, coupled with the evolution of systematic genomic and proteomic technologies, are rapidly identifying novel resistance mechanisms. In this review, we provide a historical background on drug resistance and a framework for understanding the common ways by which cancers develop resistance to targeted therapies. We further discuss advantages and disadvantages of experimental strategies that can be used to identify drug resistance mechanism(s). Significance: Increased knowledge of drug resistance mechanisms will aid in the development of effective therapies for patients with cancer. We provide a summary of current knowledge on drug resistance mechanisms and experimental strategies to identify and study additional drug resistance pathways. Cancer Discovery; 2(3); 214–26. ©2012 AACR.
Donor Lymphocyte Infusions Modulate Relapse Risk in Mixed Chimeras and Induce Durable Salvage in Relapsed Patients After T-Cell–Depleted Allogeneic Transplantation for Hodgkin's Lymphoma
Authors: Karl S. Peggs, Irfan Kayani, Noha Edwards, Panagiotis Kottaridis, Anthony H. Goldstone, David C. Linch, Rachael Hough, Emma C. Morris, Adele Fielding, Ronjon Chakraverty, Kirsty J. Thomson, Stephen Mackinnon
Journal: Journal of Clinical Oncology (2011)

Purpose Reduced-intensity conditioning has minimized nonrelapse-related mortality rates after allogeneic transplantation in patients with Hodgkin's lymphoma, and relapse has now become the major cause for treatment failure. We aimed to assess the impact of donor lymphocyte infusions (DLIs) on relapse incidence when administered for mixed chimerism and their utility as salvage therapy when given for relapse. Patients and Methods This study reports the outcomes of 76 consecutive patients with multiply relapsed or refractory Hodgkin's lymphoma who underwent allogeneic transplantation that incorporated in vivo T-cell depletion. Forty-two patients had related donors and 34 had unrelated donors. DLIs were administered in a dose-escalating fashion to 22 patients for mixed chimerism (median time of first dose, 9 months post-transplantation) and to 24 patients for relapse. Results Three-year donor lymphocyte–related mortality was 7%, relating mainly to the induction of graft-versus-host disease. Nineteen (86%) of 22 patients receiving donor lymphocytes for mixed chimerism converted to full donor status. Four-year relapse incidence was 5% in these 22 patients compared with 43% in patients who remained relapse free but full donor chimeras at 9 months post-transplantation (P = .0071). Nineteen (79%) of 24 patients receiving donor lymphocytes for relapse responded (14 complete responses, five partial responses). Four-year overall survival from relapse was 59% in recipients of donor lymphocytes, contributing to a 4-year overall survival from transplantation of 64% and a 4-year current progression-free survival of 59% in all 76 patients. Conclusion These data demonstrate the potential for allogeneic immunotherapy with donor lymphocytes both to reduce relapse risk and to induce durable antitumor responses in patients with Hodgkin's lymphoma after hematopoietic stem-cell transplantation that incorporates in vivo T-cell depletion.
Immunization with a Peptide Surrogate for Double-stranded DNA (dsDNA) Induces Autoantibody Production and Renal Immunoglobulin Deposition
Authors: Chaim Putterman, Betty Diamond
Journal: The Journal of Experimental Medicine (1998)

Anti-double-stranded DNA (dsDNA) antibodies are the serologic abnormality characteristically associated with systemic lupus erythematosus (SLE) and may play an important role in disease pathogenesis. Although the anti-dsDNA antibodies present in SLE are indicative of an antigen-driven response, the antigen has not been conclusively identified. By screening a phage peptide display library, we demonstrated previously that the decapeptide DWEYSVWLSN is specifically bound by the pathogenic murine IgG2b anti-dsDNA antibody R4A. To investigate the possibility that a protein antigen might trigger lupus-like autoimmunity, we immunized BALB/c mice with DWEYSVWLSN in adjuvant. Mice developed significant titers of IgG anti-dsDNA antibodies 2-3 wk after the initial immunization. Immunized mice also developed antibodies against some other lupus autoantigens, and immunoglobulin deposition was present in renal glomeruli at 49 d. Although an immune response to peptide and dsDNA was evident in BALB/c mice, there was little response in other inbred strains. This study demonstrates that lupus-like anti-dsDNA reactivity can be generated in nonautoimmune mice by immunization with a peptide antigen. Peptide-induced autoimmunity may prove useful in understanding the spreading of antigenic specificities targeted in SLE. However, most importantly, the demonstration that a peptide antigen can initiate a SLE-like immune response opens a new chapter on the potential antigenic stimuli that might trigger SLE.
Taking a Broader Perspective on the Benefits of Minimally Invasive Surgery
Authors: Justin B. Dimick, Andrew M. Ryan
Journal: JAMA Surgery (2013)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Elevated bronchoalveolar lavage fluid histamine levels in allergic asthmatics are associated with methacholine bronchial hyperresponsiveness.
Authors: T B Casale, D Wood, H B Richerson, S Trapp, W J Metzger, D Zavala, G W Hunninghake
Journal: Journal of Clinical Investigation (1987)

Using a sensitive single isotope enzymatic assay we measured bronchoalveolar lavage (BAL) fluid histamine in asymptomatic normal (nonallergic), allergic rhinitic, and allergic asthmatic subjects. Normal subjects were found to have little or no detectable amounts of histamine in BAL fluid (11 +/- 11 pg/ml), and few BAL fluid mast cells. In comparison, the allergic rhinitics and allergic asthmatics had much higher amounts of BAL fluid histamine (113 +/- 53 and 188 +/- 42 pg/ml, respectively), and a significantly greater number of BAL fluid mast cells. Furthermore, despite having equivalent baseline pulmonary function values, allergic asthmatics with BAL fluid histamine levels greater than 100 pg/ml required only 7 +/- 2 breath units of methacholine to induce a 20% drop in forced expiratory volume in 1 s (FEV1) (PD20FEV1) while asthmatics with BAL fluid histamine levels less than 100 pg/ml required 49 +/- 19 breath units (P less than 0.05). These data suggest that allergic asthmatics have ongoing lung mast cell degranulation that might contribute to the etiology of airway hyperresponsiveness.
The A2B adenosine receptor protects against inflammation and excessive vascular adhesion
Authors: D. Yang
Journal: Journal of Clinical Investigation (2006)

Adenosine has been described as playing a role in the control of inflammation, but it has not been certain which of its receptors mediate this effect. Here, we generated an A2B adenosine receptor–knockout/reporter gene–knock-in (A2BAR-knockout/reporter gene–knock-in) mouse model and showed receptor gene expression in the vasculature and macrophages, the ablation of which causes low-grade inflammation compared with age-, sex-, and strain-matched control mice. Augmentation of proinflammatory cytokines, such as TNF-α, and a consequent downregulation of IκB-α are the underlying mechanisms for an observed upregulation of adhesion molecules in the vasculature of these A2BAR-null mice. Intriguingly, leukocyte adhesion to the vasculature is significantly increased in the A2BAR-knockout mice. Exposure to an endotoxin results in augmented proinflammatory cytokine levels in A2BAR-null mice compared with control mice. Bone marrow transplantations indicated that bone marrow (and to a lesser extent vascular) A2BARs regulate these processes. Hence, we identify the A2BAR as a new critical regulator of inflammation and vascular adhesion primarily via signals from hematopoietic cells to the vasculature, focusing attention on the receptor as a therapeutic target.
Practical paediatric gastroenterology
Authors: A. S Ncneish
Journal: Gut (1984)

This book, the latest in the Postgraduate Paediatric Series published by Butterworths, has the stated intention of providing a very practical yet up to date approach to paediatric gastroenterology that would be appropriate for trainee paediatricians, established paediatricians, and general practitioners.The authors, from England (ex-Australia), Canada, and the USA have aimed 'to bridge the North Atlantic by producing a text that would take account of practices in our three countries in this rapidly advancing subject where clinical practice may vary from centre to centre'.They have succeeded admirably in their aim in a well produced volume of 400 pages and moderate price.In the small but growing world of paediatric gastroenterology, it is likely that, not only will the authors be friends of each other, but (as in this case) they will be friends of the reviewer as well.One can therefore look for evidence of personal hobby horsesthere are a few, and none the worse for that, in a generally well balanced text.One can have the fun of 'looking for the join' -spotting which chapters were written by which authors -not a difficult task when the special interests of each author are well known.But rather easy too for the general reader to detect which chapters emanated from the North American continent -why is it that, in general, authors from North America refer to the European literature so parsimoniously?The text is divided into two parts.An excellent section on gastrointestinal symptoms and signs in childhood is followed by a categorised account of specific disease entities.Each chapter has a short list of important references.Common disorders are given their proper place, but the unusual are covered briefly too, thus making the book a very useful addition to the library of the practising paediatric gastroenterologist.The brief chapter on diarrhoeal disease in developing communities by Michael Rowland (MRC, The Gambia) serves to remind us, in Jon Rohde's memorable phrase, of the need to 'take science where the diarrhoea is'.
A Prospective Study of Pigmentation, Sun Exposure, and Risk of Cutaneous Malignant Melanoma in Women
Authors: M. B. Veierod, E. Weiderpass, M. Thorn, J. Hansson, E. Lund, B. Armstrong, H.-O. Adami
Journal: JNCI Journal of the National Cancer Institute (2003)

Background: Although sun exposure is an established cause of cutaneous malignant melanoma, possible interactions with host factors remain incompletely understood. Here we report the first results from a large prospective cohort study of pigmentation factors and sun exposure in relation to melanoma risk. Methods: The Women's Lifestyle and Health Cohort Study included 106 379 women from Norway and Sweden who were aged 30–50 years in 1991 or 1992 when they completed an extensive questionnaire on personal characteristics and exposures. Linkages to national registries ensured complete follow-up through December 31, 1999. Poisson regression models were used to estimate relative risks (RRs). All statistical tests were two-sided. Results: During an average follow-up of 8.1 years, 187 cases of melanoma were diagnosed. Risk of melanoma was statistically significantly associated with increasing body surface area (RR for ⩾1.79 m2 versus ⩽1.61 m2 = 1.60, 95% confidence interval [CI] = 1.03 to 2.48; Ptrend = .02), number of large asymmetric nevi on the legs (RR for ⩾7 nevi versus 0 nevi = 5.29, 95% CI = 2.33 to 12.01; Ptrend<.001), hair color (RR for red versus dark brown or black = 4.05, 95% CI = 2.11 to 7.76; Ptrend<.001), sunburns per year at ages 10–19, 20–29, and 30–39 years (Ptrend<.001, Ptrend = .03, and Ptrend = .05, respectively), and use of a device that emits artificial light (solarium) one or more times per month (P = .04). Conclusions: Our results confirm previous findings that hair color, number of nevi on the legs, and history of sunburn are risk factors for melanoma and suggest that use of a solarium is also associated with melanoma risk. Adolescence and early adulthood appear to be among the most sensitive age periods for the effects of sunburn and solarium use on melanoma risk. However, it may be too early to see the full effect of adult exposures in this cohort.