tbuckley/cabot-search huggingface dataset:
Anti-Golgi autoantibodies are not clinically associated with systemic autoimmune diseases
Authors: P. Vermeersch, K. Van den Bergh, D. Blockmans, R. Westhovens, X. Bossuyt
Journal: Annals of the Rheumatic Diseases (2010)

Anti-Golgi antibodies were first described in 1982 in a patient with Sjogren's syndrome (SjS) with a lymphoma.1 They have mainly been reported in patients with SjS and systemic lupus erythematosus (SLE),2 3 but also in patients with other systemic autoimmune diseases such as rheumatoid arthritis4 and non-autoimmune disorders such as idiopathic cerebellar ataxia5 and HIV infection.6 Transient low titres have also been reported in patients with a probable viral infection.7

Anti-Golgi antibodies are rare3 and give a characteristic speckled staining on indirect immunofluorescence composed of irregular granules adjacent to one side of the nucleus. Different autoantigens have been identified including giantin/macrogolgin and different golgins,8 but …
Deficiency in the Catalytic Subunit of DNA-Dependent Protein Kinase Causes Down-Regulation of ATM
Authors: Yuanlin Peng, Rick G. Woods, Heather Beamish, Ruiqiong Ye, Susan P. Lees-Miller, Martin F. Lavin, Joel S. Bedford
Journal: Cancer Research (2005)

Abstract Previous reports have suggested a connection between reduced levels of the catalytic subunit of DNA-dependent protein kinases (DNA-PKcs), a component of the nonhomologous DNA double-strand breaks end-joining system, and a reduction in ATM. We studied this possible connection in other DNA-PKcs–deficient cell types, and following knockdown of DNA-PKcs with small interfering RNA, Chinese hamster ovary V3 cells, lacking DNA-PKcs, had reduced levels of ATM and hSMG-1, but both were restored after transfection with PRKDC. Atm levels were also reduced in murine scid cells. Reduction of ATM in a human glioma cell line lacking DNA-PKcs was accompanied by defective signaling through downstream substrates, post-irradiation. A large reduction of DNA-PKcs was achieved in normal human fibroblasts after transfection with two DNA-PKcs small interfering RNA sequences. This was accompanied by a reduction in ATM. These data were confirmed using immunocytochemical detection of the proteins. Within hours after transfection, a decline in PRKDC mRNA was seen, followed by a more gradual decline in DNA-PKcs protein beginning 1 day after transfection. No change in ATM mRNA was observed for 2 days post-transfection. Only after the DNA-PKcs reduction occurred was a reduction in ATM mRNA observed, beginning 2 days post-transfection. The amount of ATM began to decline, starting about 3 days post-treatment, then it declined to levels comparable to DNA-PKcs. Both proteins returned to normal levels at later times. These data illustrate a potentially important cross-regulation between the nonhomologous end-joining system for rejoining of DNA double-strand breaks and the ATM-dependent damage response network of pathways, both of which operate to maintain the integrity of the genome.
CD8+ T Cells Induce Complete Regression of Advanced Ovarian Cancers by an Interleukin (IL)-2/IL-15–Dependent Mechanism
Authors: Taimei Yang, Erika M. Wall, Katy Milne, Patty Theiss, Peter Watson, Brad H. Nelson
Journal: Clinical Cancer Research (2007)

Abstract Purpose: In vitro studies suggest that ovarian cancer evades immune rejection by fostering an immunosuppressive environment within the peritoneum; however, the functional responses of ovarian cancer–specific T cells have not been directly investigated in vivo. Therefore, we developed a new murine model to enable tracking of tumor-specific CD8+ T-cell responses to advanced ovarian tumors. Experimental Design: The ovarian tumor cell line ID8 was transfected to stably express an epitope-tagged version of HER-2/neu (designated NeuOT-I/OT-II). After i.p. injection into C57BL/6 mice, ID8 cells expressing NeuOT-I/OT-II gave rise to disseminated serous adenocarcinomas with extensive ascites. CD8+ T cells expressing a transgenic T-cell receptor specific for the OT-I epitope of NeuOT-I/OT-II were adoptively transferred into tumor-bearing mice, and functional responses were monitored. Cytokine signaling requirements were evaluated by comparing the responses of wild-type donor T cells with those with genetic deletion of the interleukin (IL)-2/IL-15 receptor β subunit (CD122) or the IL-2 receptor α subunit (CD25). Results: On adoptive transfer into tumor-bearing hosts, wild-type OT-I T cells underwent a striking proliferative response, reaching peak densities of ∼40% and ∼90% of CD8+ T cells in peripheral blood and ascites, respectively. OT-I cells infiltrated and destroyed tumor tissue, and ascites completely resolved within 10 days. By contrast, CD122−/− OT-I cells and CD25−/− OT-I cells proliferated in blood but failed to accumulate in ascites or tumor tissue or induce tumor regression. Conclusions: Contrary to expectation, advanced ovarian cancers can support extraordinary CD8+ T-cell proliferation and antitumor activity through an IL-2/IL-15–dependent mechanism.
Structural changes in the achilles tendon in response to a marathon: ultrasonographically detectable changes immediately and at 2 weeks postmarathon
Authors: A Tardioli
Journal: British Journal of Sports Medicine (2011)

Background The Achilles tendon undergoes prolonged, repetitive, submaximal loading during endurance running. The acute effects of endurance running on the Achilles tendon are unclear. Hypothesis Structural abnormalities and Doppler flow are common in highly trained endurance runners. A marathon may lead to acute structural changes in the Achilles, including change in diameter and increased Doppler flow. Study design Prospective cohort study Methods 41 Achilles tendons in 21 marathon runners were examined with grey-scale and colour Doppler ultrasound (US) before and immediately after the London Marathon, 2010. Six females and 15 males, mean age 40 years (±13) were included. 17 tendons were re-examined at 16 days (±1.6) postmarathon. Anteroposterior (AP) diameter (mm), grey-scale pathology (present, absent) and Doppler flow (present, absent) were measured. Results Mean race time was 03:45 h (±33 min). US examination revealed 14 of 41 tendons (34%) had abnormalities before the marathon. After the marathon, mean tendon diameter decreased significantly in both normal and abnormal tendons (53 mm–47 mm, p=0.005). Tendon diameter returned to premarathon thickness after 16 days (±1.6 days). Doppler flow was present in seven of 41 tendons (17%) before the race. This did not significantly increase in direct response to the marathon (p=0.41). There was an association between abnormal tendons and faster marathon times (p=0.005). Conclusions About 1/3 of the runners had structural abnormalities at baseline which did not increase immediately after the marathon. AP tendon diameter significantly decreased in normal and abnormal tendons immediately after the race. Tendon thickness appears to return to baseline at 2 weeks postmarathon.
Corticosteroid Metabolism and Rheumatoid Arthritis
Authors: H. F. West
Journal: Annals of the Rheumatic Diseases (1957)

Steroid research was begun at this Centre 6 years ago in the expectation that it would contribute to our knowledge of the pathogenesis of rheumatoid arthritis.Much has been learnt since then of the secretion and metabolism of the adrenocortical hormones in health and disease.The object of this paper is to take stock of the present position vis-a-vis rheumatoid arthritis.Why should interest have been taken in the adrenal cortex and its secretions when it was already known that cortisone was neither a cure nor a form of replacement therapy for rheumatoid arthritis?The reasons why Philip Hench turned his attention to the adrenal cortex 10 years ago are as valid now as they were then.To-day's reasons may be sum- marized as follows:A. The Absence of Environmental Determinants The rheumatoid arthritic's environment has been studied in considerable detail (E.R.C., 1950), and no suggestion has emerged of the existence of any environmental prerequisite.A survey of rheumatoid arthritis around the world shows that it occurs under the most diverse conditions, no immune region or race having yet been discovered.It has often been
Prevalence and correlates of airflow obstruction in 317 000 never-smokers in China
Authors: Margaret Smith, Liming Li, Mareli Augustyn, Om Kurmi, Junshi Chen, Rory Collins, Yu Guo, Yabin Han, Jingxin Qin, Guanqun Xu, Jian Wang, Zheng Bian, Gang Zhou, Richard Peto, Zhengming Chen
Journal: European Respiratory Journal (2014)

In China, the burden of chronic obstructive disease (COPD) is high in never-smokers but little is known about its causes in this group. We analysed data on 287 000 female and 30 000 male never-smokers aged 30–79 years from 10 regions in China, who participated in the China Kadoorie Biobank baseline survey (2004–2008). Prevalence of airflow obstruction (AFO) (pre-bronchodilator forced expiratory volume in 1 s (FEV 1 )/forced vital capacity (FVC) &lt;0.7 and below the lower limit of normal (LLN)) was estimated, by age and region. Cross-sectional associations of AFO (FEV 1 /FVC &lt;0.7), adjusted for confounding, were examined. AFO prevalence defined as FEV 1 /FVC &lt;0.7 was 4.0% in females and 5.1% in males (mean ages 51 and 54 years, respectively). AFO prevalence defined as FEV 1 /FVC &lt;LLN was 5.9% and 5.2%, respectively. In females, odds ratios of AFO were positively associated with lower household income (1.63, 95% CI 1.55–1.72 for lowest versus highest income groups), prior tuberculosis (2.36, 95% CI 2.06–2.71), less education (1.17, 95% CI 1.12–1.23 for no schooling versus college education), rural region and lower body mass index. AFO was positively associated with cooking with coal but not with other sources of household air pollution. Associations were similar for males. AFO is prevalent in Chinese never-smokers, particularly among those with low socioeconomic status or prior tuberculosis, and in rural males.
Complement Activation and Prognosis in Patients With Type 2 Diabetes and Myocardial Infarction
Authors: Linda G. Mellbin, Mette Bjerre, Steffen Thiel, Troels K. Hansen
Journal: Diabetes Care (2012)

The activation of the complement system may be involved in the pathology of myocardial infarction (MI) and type 2 diabetes. To explore their potential as prognostic markers, we characterized two factors in the complement cascade, the end product sC5b-9 and the mannose-binding lectin-associated Ser protease-2 (MASP-2), in type 2 diabetic patients with suspected MI.Plasma sC5b-9 and MASP-2 were determined in patients with MI and type 2 diabetes (n = 397; median age 70; male 68%). The adjudicated end points were cardiovascular events (CVEs), including cardiovascular mortality and nonfatal MI or stroke.The median sC5b-9 was 134 μg/L (interquartile range [IQR] 101-190 μg/L) and the median MASP-2 was 333 μg/L (IQR 235-463 μg/L), with no significant correlation between them. Women had higher sC5b-9 than men (median 152 vs. 130 μg/L; P = 0.02). Both sC5b-9 and MASP-2 were correlated to age and creatinine clearance, while MASP-2 was also correlated to BMI. During a median follow-up of 2.4 years, CVEs occurred in 141 patients (36%). Both sC5b-9 (hazard ratio 1.37 [95% CI 1.13-1.65]; P < 0.01) and MASP-2 (0.68 [0.51-0.92]; P = 0.01) predicted CVEs in unadjusted analyses. After multiple adjustments, the predictive capacity remained for sC5b-9 (1.30 [1.02-1.66]; P = 0.04) but not for MASP-2.In type 2 diabetic patients with MI, high levels of sC5b-9 predict future CVE. This indicates that the complement system may play a significant role in the pathology of the subsequent myocardial damage and that the pathways leading to complement activation warrant further exploration as potential therapeutic targets to improve the prognosis for these patients.
Cardiac oxidative stress in acute and chronic isoproterenol-infused rats
Authors: G ZHANG, S KIMURA, A NISHIYAMA, T SHOKOJI, M RAHMAN, L YAO, Y NAGAI, Y FUJISAWA, A MIYATAKE, Y ABE
Journal: Cardiovascular Research (2004)

Objective: Sympathetic nervous system activity in the myocardium is increased in patients with heart failure. However, the in vivo mechanisms responsible for β-adrenoceptor-mediated cardiac hypertrophy or remodeling remain unclear. This study aimed to clarify the role of reactive oxygen species (ROS) in mitogen-activated protein (MAP) kinase activation and tissue remodeling of the heart of isoproterenol (ISO)-infused rats.
Large Cell Neuroendocrine Carcinomas (Lcnec) of the Lung: Pathologic Features, Treatment and Outcomes
Authors: J. Naidoo, M.L. Santos-Zabala, T. Iyriboz, K. Woo, C.S. Sima, J.J. Fiore, M. Kris, S.R. Veach, G.J. Riely, A. Iqbal, S. Smith-Marrone, I.S. Sarkaria, L.M. Krug, C.M. Rudin, N. Rekhtman, M.C. Pietanza
Journal: Annals of Oncology (2014)
Pneumococcal capsular antigen detection and pneumococcal serology in patients with community acquired pneumonia.
Authors: W G Boersma, A Lowenberg, Y Holloway, H Kuttschrutter, J A Snijder, G H Koeter
Journal: Thorax (1991)

BACKGROUND: Methods to determine the microbial cause of community acquired pneumonia include detection of pneumococcal antigen and measurement of pneumococcal capsular antibody response. Their usefulness compared with conventional microbiological techniques was investigated in patients with pneumonia, some of whom had been treated with antibiotics. METHODS: Pneumococcal capsular antigen was detected by latex agglutination in sputum and the results compared prospectively with results of conventional microbiological techniques in 90 patients with community acquired pneumonia. Serum, urine, and pleural fluid samples were also tested for antigen. Serum pneumococcal capsular antibody titres were measured. RESULTS: A diagnosis was established by conventional microbiological techniques in 53 patients, 30 of whom had pneumococcal pneumonia. The sensitivity of antigen detection in first day sputum specimens (n = 18) in those with pneumococcal pneumonia was 94%; antigen was present in 23 of the 27 patients who produced representative sputum on admission and during follow up. The specificity of antigen detection in sputum in patients with non-pneumococcal pneumonia and lung infarction was 87%. Antigen was present in 12 of 25 patients with pneumonia of unknown aetiology who produced representative sputum. Antigen was rarely detected in serum and urine, but was present in pleural fluid in three of four patients with pneumococcal pneumonia and in all four patients with pneumonia of unknown aetiology. Pneumococcal antigen remained detectable in patients treated with antibiotics. Pneumococcal capsular antibody detection was as specific (85%) as antigen detection, but had a lower sensitivity (50%). CONCLUSION: Pneumococcal antigen detection in sputum or pleural fluid is of value in making a rapid diagnosis and provides an additional diagnostic result in patients with pneumococcal pneumonia, especially those receiving antibiotic treatment.
Sleep Complaints and Depression in an Aging Cohort: A Prospective Perspective
Authors: R E Roberts, S J Shema, G A Kaplan, W J Strawbridge
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: Most research on the association between sleep disturbances and depression has looked at cross-sectional data. The authors used two waves of data from a panel study of community residents aged 50 years or more to investigate this issue prospectively. METHOD: Data on symptoms of major depressive episodes and sleep problems were examined for a subgroup of the 1994 and 1995 surveys of the Alameda County (California) Study (N=2,370). The authors examined the effects of age, gender, education, marital status, social isolation, functional impairment, financial strain, and alcohol use. Depression was measured with 12 items that covered the DSM-IV diagnostic criteria for major depressive episodes, including insomnia and hypersomnia. RESULTS: The prevalences were 23.1% for insomnia and 6.7% for hypersomnia in 1994. Sleep was a significant correlate of depression, as were being female, older age, social isolation, low education, financial strain, and functional impairment. When sleep problems and depression were examined prospectively, with controls for the effects of the other variables, sleep problems in 1994 predicted depression in 1995. However, other symptoms of major depressive episodes—anhedonia, feelings of worthlessness, psychomotor agitation/retardation, mood disturbance, thoughts of death—were much stronger predictors of future major depression. CONCLUSIONS: Sleep disturbance and other symptoms that are diagnostic for major depression are strongly associated with the risk of future depression. Sleep disturbance appears to be a less important predictor of depression. More epidemiologic research is needed on the relative contributions of the range of depressive symptoms to the risk of clinical depression.
Morphological variations of scar-related and spontaneous endometriosis of the skin and superficial soft tissue: A study of 71 cases with emphasis on atypical features and types of müllerian differentiations
Authors: Dmitry V. Kazakov, Ondrej Ondic, Michal Zamecnik, Ksenia V. Shelekhova, Petr Mukensnabl, Ondrej Hes, Vladimir Dvorak, Michal Michal
Journal: Journal of the American Academy of Dermatology (2007)
Epidermal Growth Factor Receptor Inhibition in Lung Cancer: Status 2012
Authors: Fred R. Hirsch, Pasi A. Jänne, Wilfried E. Eberhardt, Federico Cappuzzo, Nick Thatcher, Robert Pirker, Hak Choy, Edward S. Kim, Luis Paz-Ares, David R. Gandara, Yi-Long Wu, Myung-Ju Ahn, Tetsuya Mitsudomi, Frances A. Shepherd, Tony S. Mok
Journal: Journal of Thoracic Oncology (2013)
Transforming Growth Factor-β2 Is a Molecular Determinant for Site-Specific Melanoma Metastasis in the Brain
Authors: Chenyu Zhang, Fahao Zhang, Rachel Tsan, Isaiah J. Fidler
Journal: Cancer Research (2009)

Abstract Murine melanomas produce site-specific experimental brain metastases that reflect clinical reality. When injected into the internal carotid artery of mice, K-1735 melanoma cells produce metastatic lesions only in the brain parenchyma, whereas B16 melanoma cells and the somatic hybrid cells of B16 × K-1735 melanoma cells produce metastatic lesions only in the leptomeninges and ventricles. In the present study, we identified transforming growth factor-β2 (TGF-β2), an isoform of the TGF-β family, as a molecular determinant of melanoma cell growth in the brain parenchyma. We found that the TGF-β2 mRNA was highly expressed by the K-1735 cells, whereas the B16 cells or any B16 × K-1735 somatic cell-cell fusion hybrids have low expression. Transfection of the TGF-β2 gene into B16 cells resulted in the production of microscopic metastatic lesions in the brain parenchyma, without a decrease in metastasis to the leptomeninges or ventricles. TGF-β2 knockdown in the K-1735 melanoma cells significantly reduced metastasis to the brain parenchyma but did not induce metastasis to the leptomeninges or ventricles. These data show that TGF-β2 expression by murine melanoma cells is necessary for the establishment and growth of metastases in the brain parenchyma. [Cancer Res 2009;69(3):828–35]
Intrinsic subtype and its clinical significance in early node-negative breast cancer: Results from two randomized trials of adjuvant chemoendocrine therapy.
Authors: Ewan K.A Millar, Alan Stuart Coates, Sandra O'Toole, Cristina Selinger, Elizabeth A. Musgrove, Max Yan, Giuseppe Viale, Meredith M. Regan, Karen N. Price, Zhuoxin Sun, Monica M. Castiglione, Marco Colleoni, Richard D. Gelber, Aron Goldhirsch, Robert L. Sutherland
Journal: Journal of Clinical Oncology (2012)

504 Background: Gene expression profiling has identified four main intrinsic subtypes of breast cancer which have distinct clinical behaviours and responses to therapy. A simplified immunohistochemical (IHC) panel can provide meaningful discrimination and help guide patient management. Methods: Using tissue microarrays (TMA) created from two randomized trials of adjuvant chemoendocrine therapy in node negative early breast cancer (IBCSG VIII and IX,n= 1220) we assessed intrinsic subtype as follows: “luminal A” (LA): ER and/or PR present, Ki-67 low (&lt;median: 19%), HER2-; “Luminal B” (LB): ER and/or PR present, Ki-67 high(&gt;=19% median) and/or HER2+ (IHC 3+ or FISH amplified); HER2 enriched: ER and PR negative, HER2 positive (IHC 3+ or FISH amplified), Triple Negative (TNP): ER, PR and HER2 negative. p53+ and high cyclin D1 expression were then assessed to determine if they provided any further additive discriminatory value. Results: The standard definitions of intrinsic subtype demonstrated a significant difference in disease-free survival between the subtypes in both trials VIII and IX (p= 0.02), but this was not significant in multivariate analysis. The discrimination between luminal A and B tumors could not be improved upon by the addition of p53 or cyclin D1 expression. The standard definitions demonstrated that TNP and HER2-enriched tumors benefited from the addition of chemotherapy to endocrine therapy, but LA and LB did not. p53+ was associated with a poorer prognosis in ER+ luminal tumors but improved prognosis in ER- non-luminal tumors (Interaction p = 0.002). Conclusions: Intrinsic subtyping using a panel of ER, PR, HER2 and Ki67 provides meaningful prognostic information to help guide patient management in early breast cancer. Whilst it predicts benefit from the addition of chemotherapy in TNP and HER2-enriched tumors it did not in this series do so for LB. Although p53 status did not improve the definition of luminal tumors, p53+ appeared to have a divergent effect on outcome dependent on ER status.
Antibody-mediated vascular rejection of kidney allografts: a population-based study
Authors: Carmen Lefaucheur, Alexandre Loupy, Dewi Vernerey, Jean-Paul Duong-Van-Huyen, Caroline Suberbielle, Dany Anglicheau, Jérôme Vérine, Thibaut Beuscart, Dominique Nochy, Patrick Bruneval, Dominique Charron, Michel Delahousse, Jean-Philippe Empana, Gary S Hill, Denis Glotz, Christophe Legendre, Xavier Jouven
Journal: The Lancet (2012)
Transfusion Reactions due to Plasma Incompatibility in Dogs
Authors: J. Q. BLISS, D. G. JOHNS, A. S. V. BURGEN
Journal: Circulation Research (1959)

Plasma incompatibility was investigated as a possible factor in transfusion reactions in dogs. Urticaria, failure to retain within the circulation the equivalent of transfused plasma volume and protein, and increased gastric acid secretion almost invariably followed transfusion of plasma from another dog but not transfusion of the dog's own plasma. The cutaneous reactions were abolished and the retention of plasma was improved by administration of an antihistamine. Erythrocyte isoagglutinins did not appear to be involved in these reactions.