tbuckley/cabot-search huggingface dataset:
Association Between Raised Blood Pressure and Dysglycemia in Hong Kong Chinese
Authors: Bernard M.Y. Cheung, Nelson M.S. Wat, Annette W.K. Tso, Sidney Tam, G. Neil Thomas, Gabriel M. Leung, Hung Fat Tse, Jean Woo, Edward D. Janus, Chu Pak Lau, Tai Hing Lam, Karen S.L. Lam
Journal: Diabetes Care (2008)

To investigate the association between raised blood pressure and dysglycemia.We studied the association between raised blood pressure and dysglycemia in 1,862 subjects in the Hong Kong Cardiovascular Risk Factor Prevalence Study cohort. We determined the factors predicting the development of diabetes and hypertension in 1,496 subjects who did not have either condition at baseline.Diabetes and hypertension were both related to age, obesity indexes, blood pressure, glucose, HDL cholesterol, and triglycerides. Of subjects with diabetes, 58% had raised blood pressure. Of subjects with hypertension, 56% had dysglycemia. BMI and blood glucose 2 h after a 75-g oral glucose load were independent predictors of new-onset diabetes. Age, systolic blood pressure, and 2-h glucose were independent predictors of new-onset hypertension. BMI, systolic blood pressure, and 2-h glucose were independent predictors of the development of diabetes and hypertension together.Diabetes and hypertension share common etiological factors. Patients with diabetes or hypertension should be screened and managed for the precursor of the other condition.
Targeting of Low-Dose CT Screening According to the Risk of Lung-Cancer Death
Authors: Stephanie A. Kovalchik, Martin Tammemagi, Christine D. Berg, Neil E. Caporaso, Tom L. Riley, Mary Korch, Gerard A. Silvestri, Anil K. Chaturvedi, Hormuzd A. Katki
Journal: New England Journal of Medicine (2013)

In the National Lung Screening Trial (NLST), screening with low-dose computed tomography (CT) resulted in a 20% reduction in lung-cancer mortality among participants between the ages of 55 and 74 years with a minimum of 30 pack-years of smoking and no more than 15 years since quitting. It is not known whether the benefits and potential harms of such screening vary according to lung-cancer risk.
TUMOR NECROSIS FACTOR: A Pleiotropic Cytokine and Therapuetic Target
Authors: Kevin J. Tracey, M.D, Anthony Cerami, Ph.D
Journal: Annual Review of Medicine (1994)

▪ Abstract Advances in the molecular biology of human diseases indicate that the most striking manifestations of illness may be caused not by exogenous pathogenic or tumor porducts, but rather by toxic peptides produced by the host itself. Tumor necrosis factor (TNF), a polypeptide cytokine produced during infection, injury, or invasion, has proved spivotal in triggering the lethal effects of septic shock syndrome, cachexia, and other systemic manifestations of disease. Because removing TNF from the diseased host may prevent development of the illness, this factor has recently been the focus of intensive research. This review discusses the biology of this cytokine, with particular emphasis on its potential therapeutic role in septic shock and cachexia.
CT screening for lung cancer: so near, yet so far
Authors: Naveen Dutt, Deepak T Hari
Journal: Thorax (2011)

The UK Lung Screen team in their positional statement outlined the issues to be explored by the trial on CT screening for lung cancer.1 Although it seems to be a large, well-planned study, we believe that there are some shortcomings in this study that may undermine its significance. There are several other aspects of CT screening that need to be investigated in order to determine the suitability …
Inosine Triphosphate Pyrophosphatase and Thiopurine S-Methyltransferase Genotypes Relationship to Azathioprine-Induced Myelosuppression
Authors: Zuzana Zelinkova, Luc J.J. Derijks, Pieter C.F. Stokkers, Esther W.M. Vogels, Antoine H.C. van Kampen, Wouter L. Curvers, Danny Cohn, Sander J.H. van Deventer, Daniël W. Hommes
Journal: Clinical Gastroenterology and Hepatology (2006)
Genome-wide screening of copy number alterations and LOH events in renal cell carcinomas and integration with gene expression profile
Authors: Ingrid Cifola, Roberta Spinelli, Luca Beltrame, Clelia Peano, Ester Fasoli, Stefano Ferrero, Silvano Bosari, Stefano Signorini, Francesco Rocco, Roberto Perego, Vanessa Proserpio, Francesca Raimondo, Paolo Mocarelli, Cristina Battaglia
Journal: Molecular Cancer (2008)

Clear cell renal carcinoma (RCC) is the most common and invasive adult renal cancer. For the purpose of identifying RCC biomarkers, we investigated chromosomal regions and individual genes modulated in RCC pathology. We applied the dual strategy of assessing and integrating genomic and transcriptomic data, today considered the most effective approach for understanding genetic mechanisms of cancer and the most sensitive for identifying cancer-related genes.We performed the first integrated analysis of DNA and RNA profiles of RCC samples using Affymetrix technology. Using 100K SNP mapping arrays, we assembled a genome-wide map of DNA copy number alterations and LOH areas. We thus confirmed the typical genetic signature of RCC but also identified other amplified regions (e.g. on chr. 4, 11, 12), deleted regions (chr. 1, 9, 22) and LOH areas (chr. 1, 2, 9, 13). Simultaneously, using HG-U133 Plus 2.0 arrays, we identified differentially expressed genes (DEGs) in tumor vs. normal samples. Combining genomic and transcriptomic data, we identified 71 DEGs in aberrant chromosomal regions and observed, in amplified regions, a predominance of up-regulated genes (27 of 37 DEGs) and a trend to clustering. Functional annotation of these genes revealed some already implicated in RCC pathology and other cancers, as well as others that may be novel tumor biomarkers.By combining genomic and transcriptomic profiles from a collection of RCC samples, we identified specific genomic regions with concordant alterations in DNA and RNA profiles and focused on regions with increased DNA copy number. Since the transcriptional modulation of up-regulated genes in amplified regions may be attributed to the genomic alterations characteristic of RCC, these genes may encode novel RCC biomarkers actively involved in tumor initiation and progression and useful in clinical applications.
Immunoproteasomes Shape Immunodominance Hierarchies of Antiviral Cd8+ T Cells at the Levels of T Cell Repertoire and Presentation of Viral Antigens
Authors: Weisan Chen, Christopher C. Norbury, Yunjung Cho, Jonathan W. Yewdell, Jack R. Bennink
Journal: The Journal of Experimental Medicine (2001)

Vertebrates express three cytokine-inducible proteasome subunits that are incorporated in the place of their constitutively synthesized counterparts. There is increasing evidence that the set of peptides generated by proteasomes containing these subunits (immunoproteasomes) differs from that produced by standard proteasomes. In this study, we use mice lacking one of the immunoproteasome subunits (LMP2) to show that immunoproteasomes play an important role in establishing the immunodominance hierarchy of CD8+ T cells (TCD8+) responding to seven defined determinants in influenza virus. In LMP2−/− mice, responses to the two most dominant determinants drop precipitously, whereas responses to two subdominant determinants are greatly enhanced. Adoptive transfer experiments with naive normal and transgenic TCD8+ reveal that the reduced immunogenicity of one determinant (PA224–233) can be attributed to decreased generation by antigen presenting cells (APCs), whereas the other determinant (NP366–374) is less immunogenic due to alterations in the TCD8+ repertoire, and not, as reported previously, to the decreased capacity of LMP2−/− APCs to generate the determinant. The enhanced response to one of the subdominant determinants (PB1F262–70) correlates with increased generation by LMP2−/− virus–infected cells. These findings indicate that in addition to their effects on the presentation of foreign antigens, immunoproteasomes influence TCD8+ responses by modifying the repertoire of responding TCD8+.
A Computed Tomography Scan Assessment of Regional Lung Volume in Acute Lung Injury
Authors: LOUIS PUYBASSET, PHILIPPE CLUZEL, NAN CHAO, ARTHUR S. SLUTSKY, PIERRE CORIAT, JEAN-JACQUES ROUBY
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

The lobar and cephalocaudal distribution of aerated and nonaerated lung and of PEEP-induced alveolar recruitment is unknown in acute lung injury (ALI). Dimensions of the lungs and volumes of aerated and nonaerated parts of each pulmonary lobe were measured using a computerized tomographic quantitative analysis and compared between 21 patients with ALI and 10 healthy volunteers. Distribution of PEEP-induced alveolar recruitment along the anteroposterior and cephalocaudal axis and influence of the resting volume of nonaerated lower lobes were also assessed. Anteroposterior and transverse dimensions of the lungs of the patients were similar to those of healthy volunteers, whereas cephalocaudal dimensions were reduced by more than 15%. Total lung volume (aerated plus nonaerated lung) was reduced by 27%. Volumes of upper and lower lobes were 99 and 48% of normal values. In addition to an anteroposterior gradient in the distribution of aerated and nonaerated areas, a cephalocaudal gradient was also observed. Nonaerated areas were predominantly found in juxtadiaphragmatic regions. PEEP-induced alveolar recruitment was more pronounced in nondependent than in dependent regions and in cephalad than in caudal regions. A significant correlation between resting volume of nonaerated lower lobes and regional PEEP-induced alveolar recruitment was observed. In ALI, loss of lung volume involves predominantly lower lobes. The thorax shortens along its cephalocaudal axis. PEEP-induced alveolar recruitment predominates in nondependent and cephalad lung regions and is inversely correlated with the resting volume of nonaerated lung.
Differences in the repertoire of the Lewis rat T cell response to self and non-self myelin basic proteins.
Authors: M P Happ, E Heber-Katz
Journal: The Journal of Experimental Medicine (1988)

We have examined the fine specificity of a panel of cloned T cell hybridomas generated from Lewis rats immunized with guinea pig (GP) or Lewis rat myelin basic protein (MBP) to determine the autoimmune T cell repertoire that develops in experimental allergic encephalomyelitis (EAE). This analysis has demonstrated that GP MBP, which was approximately 10-fold more potent for EAE induction than the autologous rat MBP, produced a population in which almost one-fourth of the members responded to GP-unique determinants and displayed no crossreactivity on the self antigen. The remaining majority of GP MBP-induced clones were specific for the 68-88 encephalitogenic determinant and could be subdivided into three groups based on their varying responses to the 68-88 peptide and rat and rabbit MBPs. Surprisingly, one of these groups showed equal reactivity to GP and rat MBPs. In contrast, the clonotype composition of the T cell population induced by rat MBP was quite different. One-half of these clones comprised a single group responding to the 68-88 determinant, reacting equally with GP and rat MBP. All of these responded to the same range of antigen concentrations as their GP-induced counterparts. The remaining half of that population contained a collection of clones that was nearly as encephalitogenic as the 68-88 population after propagation as a short-term T cell line. These clones were specific for at least three distinct antigenic determinants, all displaying extensive cross-species reactivity, and required as little or less rat MBP for maximal stimulation as did the 68-88-reactive clones. We therefore conclude that the T cell repertoire for MBP does include clones with reactivity to both 68-88 and non-68-88 determinants of GP and rat MBPs, and that both MBPs appear to be equally capable of stimulating these clones in vitro. However, the differences in the clonotype composition of the populations induced by immunization with these two antigens suggest that rat and GP MBPs are subject to different immunoregulatory constraints in the animal and may account for the difference in the encephalitogenic potential of these two antigens.
Local production and detection of (specific) IgE in nasal B-cells and plasma cells of allergic rhinitis patients
Authors: A KleinJan, J.g Vinke, L.W.F.m Severijnen, W.j Fokkens
Journal: European Respiratory Journal (2000)

Allergic diseases are characterized by allergic complaints in the shock organ and specific immunoglobulin (Ig)E in serum. Literature data indicate that the nasal mucosa itself could produce at least a large part of the specific IgE in allergic rhinitis patients. In order to investigate this hypothesis, nasal mucosal biopsies from the inferior turbinate were taken from symptomatic grass pollen allergic rhinitis patients, symptomatic house dust mite allergic rhinitis patients and nonallergic healthy controls, confirmed by radioallergosorbent test and skin-prick test. Immunohistochemical double-staining was performed for B-cells (CD19) with IgE, plasma cells (CD138) with IgE and plasma cells with biotinylated allergens. Significantly more IgE-positive B-cells and IgE-positive plasma cells were found in the nasal mucosa of allergic patients than in that of nonallergic controls. Double staining with biotinylated allergens and plasma cells showed allergen-positive plasma cells in the nasal mucosa of allergic patients and no allergen-positive plasma cells in the nasal mucosa of nonallergic patients. Blocking experiments using polyclonal antibodies directed against IgE showed a significant reduction in the number of allergen-positive cells in contrast to experiments using polyclonal antibodies directed against IgG, IgA or IgM. This study describes new evidence that specific immunoglobulin E is produced locally in the nasal mucosa in patients with seasonal allergic rhinitis and perennial allergic rhinitis, but not in nonallergic controls.
C1q enhancement of antibody-dependent granulocyte-mediated killing of nonphagocytosable targets in vitro.
Authors: A Hamada, J Young, R A Chmielewski, B M Greene
Journal: Journal of Clinical Investigation (1988)

A possible role for C1q in antibody-dependent granulocyte-mediated killing of nonphagocytosable targets was investigated utilizing IgG-dependent granulocyte cytotoxicity directed against microfilariae of Dirofilaria immitis. Granulocyte-mediated killing of microfilariae is enhanced by addition of fresh serum. Lack of C4 did not significantly reduce the observed increase in cytotoxicity. The addition of highly purified monomeric human Clq (0.2 microgram/ml) in the presence of immune IgG resulted in a two- to fivefold enhancement of killing (P less than 0.025). C1q enhancement of killing occurred in the absence of fluid-phase IgG, but killing was significantly less than when both fluid-phase IgG and C1q were present. The effect of C1q was inhibited by the addition of solubilized type I collagen (44-92% inhibition of killing, P less than 0.05). Significant 125I-Clq binding to microfilariae occurred only in the presence of immune IgG. In addition, C1q in concentrations ranging from 0.5 to 2.0 micrograms/ml resulted in a dose-dependent increase in binding of 125I-immune IgG to microfilariae. Finally, when purified C1q was added to preopsonized, washed microfilariae, granulocyte production of superoxide was increased from 0.25 +/- 0.07 to 0.68 +/- 0.07 nm/10(6) cells.10 min (P less than 0.01). These results describe a novel functional role for C1q in enhancement of antibody-dependent cellular cytotoxicity towards nonphagocytosable targets.
AB0724 Isotretinoin Induced Bilateral Sacroiliitis: CASE Report
Authors: N.A. Bilecik, S. Tuna, S. Alan
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Isotretinoin, a retinoid indicated for the treatment of severe cystic acne, has been associated with adverse effects,including musculoskeletal symptoms. Reported here is a case of bilateral sacroiliitis related to isotretinoin use. Isotretinoin may cause sacroiliitis development or trigger it in healthy people. We advise rheumatologists to be aware of this side effect. <h3>Objectives</h3> Isotretinoin, a retinoid indicated for the treatment of severe cystic acne, has been associated with adverse effects,including musculoskeletal symptoms. Reported here is a case of bilateral sacroiliitis related to isotretinoin use which completely resolved following discontinuation of the medication. <h3>Methods</h3> A 18 year old man was treated for acne affecting the back and face with oral isotretinoin. He had no previous medical problems apart from the onset with puberty of severe acne vulgaris of the face and back. Isotretinoin was commenced 10 weeks later he experienced back and sacroiliiac pain, restricting his participation in sporting activities. There was no history of psoriasis, uveitis or inflammatory bowel disease. The patient was taking no other medications. On examination he had decrease lomber schober,sacroiliac tenderness. MRI showed moderate to severe relatively symmetrical sacroiliitis with moderate joınt effusions and florid bone marrow oedema in the anterosuperior aspect of the sacroiliac joints. The isotretinoin was ceased and the patient responded to slow release naproxen 1000 mg daily and physiotherapy. Eight weeks later he was free of symptoms. A repeat MRI performed 10 weeks later showed no evidence of sacroiliitis – no effusions, synovitis or abnormal one marrow signal. <h3>Results</h3> Bilateral symmetrical sacroiliitis can be seen in seronegative spondyloarthropathies. The patient had no infectious conditions capable of initiating reactive arthritis and lacked both a history and symptoms of inflammatory bowel disease psoriasis, uveitis, conjunctivitis or perıpheral arthritis inconsistent with ankyilosing spodylitis, enteropathic arthropathies and psoriatic arthropathy. Synovial and/or bone inflammatory symptoms may develop in closely related conditions featuring acne or acral pustules. These symptoms may appear spontaneously or be triggered by isotretinoin. Previous cases of sacroiliitis in patients treated with isotretinoin for acne have not been able to conclusively attribute the condition to either isotretinoin or the patients9 acne. We report here that isotretinoin treatment is usually used in acne treatment, may cause sacroiliitis development or trigger it in healthy people. We advise rheumatologists to be aware of this side effect. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5208
TLR4 links innate immunity and fatty acid–induced insulin resistance
Authors: Hang Shi, Maia V. Kokoeva, Karen Inouye, Iphigenia Tzameli, Huali Yin, Jeffrey S. Flier
Journal: Journal of Clinical Investigation (2006)

TLR4 is the receptor for LPS and plays a critical role in innate immunity. Stimulation of TLR4 activates proinflammatory pathways and induces cytokine expression in a variety of cell types. Inflammatory pathways are activated in tissues of obese animals and humans and play an important role in obesity-associated insulin resistance. Here we show that nutritional fatty acids, whose circulating levels are often increased in obesity, activate TLR4 signaling in adipocytes and macrophages and that the capacity of fatty acids to induce inflammatory signaling in adipose cells or tissue and macrophages is blunted in the absence of TLR4. Moreover, mice lacking TLR4 are substantially protected from the ability of systemic lipid infusion to (a) suppress insulin signaling in muscle and (b) reduce insulin-mediated changes in systemic glucose metabolism. Finally, female C57BL/6 mice lacking TLR4 have increased obesity but are partially protected against high fat diet-induced insulin resistance, possibly due to reduced inflammatory gene expression in liver and fat. Taken together, these data suggest that TLR4 is a molecular link among nutrition, lipids, and inflammation and that the innate immune system participates in the regulation of energy balance and insulin resistance in response to changes in the nutritional environment.
Long-Term Follow-Up of a Randomized Trial Comparing Concurrent Single Agent Cisplatin, Cisplatin-Based Combination Chemotherapy, or Hydroxyurea During Pelvic Irradiation for Locally Advanced Cervical Cancer: A Gynecologic Oncology Group Study
Authors: Peter G. Rose, Shamshad Ali, Edwin Watkins, J. Tate Thigpen, Gunter Deppe, Daniel L. Clarke-Pearson, Samuel Insalaco
Journal: Journal of Clinical Oncology (2007)

We report the long-term survival and toxicity of a randomized phase III study comparing cisplatin alone with cisplatin, flurouracil, and hydroxyurea versus hydroxyurea concurrent with pelvic irradiation for patients with locally advanced cervical cancer with pathologically negative para-aortic nodes.Comparisons of progression-free (PFS) and overall survival (OS) between treatment arms utilized Kaplan-Meier and log-rank statistics. Relative risk estimates adjusting for prognostic factors were determined using the Cox proportional hazards regression model. Pearson's 2 test was used to assess differences in adverse events.The analysis included 526 patients. The median follow-up among surviving patients was 106 months. Consistent with the original report, improvement in PFS and OS was evident for both cisplatin-containing arms compared with hydroxyurea (P < .001). Analogous results were seen for stage IIB and for stage III disease (each P < .025). The relative risk of progression of disease or death was 0.57 (95% CI, 0.43 to 0.75) with cisplatin and 0.51 (95% CI, 0.38 to 0.67) with cisplatin-based combination chemotherapy compared with hydroxyurea. Among 518 patients who received radiation, acute (grade 3 or 4) gastrointestinal or urologic toxicities occurred in 66 with cisplatin (19.1%) and 29 with hydroxyurea (16.8%). Delayed radiation toxicity occurred in six patients who received cisplatin (1.7%) and two who received hydroxyurea (1.2%; P = .680).Cisplatin-based chemotherapy during pelvic radiation therapy improves long-term PFS and OS among locally advanced cervical cancer patients collectively and for stage IIB and III disease, individually. There was no observed increase in late toxicity with cisplatin-based chemoradiotherapy.
Detection of small joint synovitis by ultrasonography: the learning curve of rheumatologists
Authors: M-A D'Agostino
Journal: Annals of the Rheumatic Diseases (2004)

Ultrasonography allows assessment of soft tissue structures and has become a valued tool for diagnosing synovitis.To assess the learning curve for ultrasonography in evaluating synovitis of the small joints in rheumatoid arthritis.Metacarpophalangeal (MCP), metatarsophalangeal (MTP), and proximal interphalangeal (PIP) joints were evaluated using ultrasonography (Esaote AU 5 Epi, linear probe 10-13 MHz) by four rheumatologists, the first being experienced (senior), the others having no (fellows 1 and 2) or little (fellow 3) experience in ultrasonography. For each fellow, the learning curve was divided into blocks. In each block the fellow examined five consecutive patients with the senior; then, blinded to the senior's results, two further patients alone (seven patients examined per block). For each evaluation, the MCP, PIP, and MTP joints were individually tagged as having synovitis or not. The ultrasonography results were compared between fellow and senior for the two last patients of each block, using proportions of agreement and kappa statistics.70 patients were evaluated (seven practice patients, followed by nine blocks). For fellows 1 and 2, the proportions of agreement were respectively 42% and 47% (kappa = 0 and 0) at the first evaluation, and rose progressively to 82% and 82% (kappa = 0.63 and 0.62) at the ninth evaluation. For fellow 3, initially good results were followed by decreased accuracy.Detecting synovitis of the MCP, PIP, and MTP joints using ultrasonography can be done accurately by rheumatologists initially not experienced in this technique. At least 70 examinations were necessary to develop competence.