tbuckley/cabot-search huggingface dataset:
Sarcoid arthritis: clinical characteristics, diagnostic aspects, and risk factors
Authors: H Visser
Journal: Annals of the Rheumatic Diseases (2002)

Objectives: (<i>a</i>) To describe the clinical characteristics of acute sarcoid arthritis and the diagnostic value of its presenting clinical features; (<i>b</i>) to evaluate whether disease onset is seasonal; and (<i>c</i>) to evaluate whether smoking behaviour or the presence of HLA class II alleles is a risk factor for the disease. Methods: 579 consecutive patients with recent onset arthritis who had been newly referred to a rheumatology outpatient clinic were included in a prospective cohort study. The presenting clinical features, the smoking behaviour, and the results of HLA-DQ and HLA-DR DNA typing of 55 patients with sarcoid arthritis, 524 patients with other arthritides of recent onset, and samples of the normal population were compared. Results: In all cases the disease showed a self limiting arthritis and overall good prognosis. The diagnostic ability of a combination of four clinical features—symmetrical ankle arthritis, symptoms of less than two months, age below 40 years, and erythema nodosum—was exceptionally high. When test positivity is defined as the presence of at least three of four criteria the set rendered a sensitivity of 93%, a specificity of 99%, a positive predictive value of 75%, and a negative predictive value of 99.7%. The disease clustered in the months March–July. The disease was negatively associated with smoking (odds ratio (OR) 0.09; 95% confidence interval (95% CI) 0.02 to 0.37) and positively associated with the presence of the DQ2 (DQB1*0201)-DR3 (DRB1*0301) haplotype (OR 12.33; 95% CI 5.97 to 25.48). Conclusion: The disease entity acute sarcoid arthritis has highly diagnostic clinical features. The seasonal clustering, the protective effect of smoking, and the association with specific HLA class II antigens support the hypothesis that it results from exposure of susceptible hosts to environmental agents through the lungs.
Allosteric Modulators of Steroid Hormone Receptors: Structural Dynamics and Gene Regulation
Authors: Raj Kumar, Iain J. McEwan
Journal: Endocrine Reviews (2012)

Steroid hormones are synthesized from cholesterol primarily in the adrenal gland and the gonads and play vital roles in normal physiology, the control of development, differentiation, metabolic homeostasis, and reproduction. The actions of these small lipophilic molecules are mediated by intracellular receptor proteins. It is just over 25 yr since the first cDNA for steroid receptors were cloned, a development that led to the birth of a superfamily of ligand-activated transcription factors: the nuclear receptors. The receptor proteins share structurally and functionally related ligand binding and DNA-binding domains but possess distinct N-terminal domains and hinge regions that are intrinsically disordered. Since the original cloning experiments, considerable progress has been made in our understanding of the structure, mechanisms of action, and biology of this important class of ligand-activated transcription factors. In recent years, there has been interest in the structural plasticity and function of the N-terminal domain of steroid hormone receptors and in the allosteric regulation of protein folding and function in response to hormone, DNA response element architecture, and coregulatory protein binding partners. The N-terminal domain can exist as an ensemble of conformers, having more or less structure, which prime this region of the receptor to rapidly respond to changes in the intracellular environment through hormone binding and posttranslation modifications. In this review, we address the question of receptor structure and function dynamics with particular emphasis on the structurally flexible N-terminal domain, intra- and interdomain communications, and the allosteric regulation of receptor action.
Vascular Abnormalities, Paraoxonase Activity, and Dysfunctional HDL in Primary Antiphospholipid Syndrome
Authors: Marietta Charakida
Journal: JAMA (2009)

Accelerated atherosclerosis has been described in antiphospholipid syndrome, but the vascular abnormalities and the underlying mechanisms remain unclear.To compare vascular structure and function in patients with positive antiphospholipid antibodies (aPL) with controls and to assess their relationship with paraoxonase activity.A cross-sectional study of 77 women with positive antiphospholipid antibodies from a lupus outpatient clinic in London, England (90% of the eligible population) and 77 controls matched on frequency basis for age and cardiovascular risk factors between June 2006 and April 2009. Carotid intima media thickness (CIMT), flow-mediated dilatation, pulse wave velocity, and paraoxonase activity were measured in all patients. Anti-inflammatory and antioxidant properties of high-density lipoprotein (HDL) were examined.CIMT, pulse wave velocity, flow-mediated dilatation, and paraoxonase.Women with aPL had greater CIMT and pulse wave velocity compared with controls (mean [SD], 0.75 [0.16] vs 0.64 [0.09] mm; 95% confidence interval [CI], -0.14 to -0.06; P < .001; and 9.2 [1.6] vs 8.5 [1.8] m/s; 95% CI, -1.14 to -0.06; P = .04) and lower flow-mediated dilatation (6.2% [4.1%] vs 9.6% [4.2%]; 95% CI, 2.02%-4.69%; P < .001). Paraoxonase activity was lower in women with aPL vs controls (median [interquartile range], 91.2 [64.3-105.1] vs 103.0 [80.5-111.5] micromol p-nitrophenol/L/serum/min; 95% CI, 0.004-0.007; P = .005) and was inversely associated with CIMT and pulse wave velocity in women with aPL (standardized beta coefficient = -0.4 and -0.3, respectively; P < .05 for both), but not in the control group. High-density lipoprotein from women with aPL inhibited endothelial nitric oxide production in human aortic endothelial cells, in contrast with controls. The beneficial effects of HDL from women with aPL on vascular cell adhesion molecule 1 expression, superoxide production, and monocyte adhesion following activation of human aortic endothelial cells were largely blunted.Compared with controls, women with aPL had greater functional and structural arterial abnormalities, which were associated with lower activity of paraoxonase. In patients with aPL, HDL reduced nitric oxide bioavailability and had impaired anti-inflammatory and antioxidant properties.
Viruses Perturb Lymphocyte Functions: Selected Principles Characterizing Virus-Induced Immunosuppression
Authors: M B McChesney, M B A Oldstone
Journal: Annual Review of Immunology (1987)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Effect of Trichloropropene Oxide on the Ability of Polyaromatic Hydrocarbons and Their “K-Region” Oxides To Initiate Skin Tumors in Mice and To Bind to DNA In Vitro2
Authors: David L. Berry, Thomas J. Siaga, Aurora Viaje, Neil M. Wilson, John DiGiovanni, Mont R. Juchau, James K. Selkirk
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Effect of Trichloropropene Oxide on the Ability of Polyaromatic Hydrocarbons and Their “K-Region” Oxides To Initiate Skin Tumors in Mice and To Bind to DNA In Vitro Get access David L. Berry, David L. Berry Search for other works by this author on: Oxford Academic PubMed Google Scholar Thomas J. Siaga, Thomas J. Siaga Search for other works by this author on: Oxford Academic PubMed Google Scholar Aurora Viaje, Aurora Viaje Search for other works by this author on: Oxford Academic PubMed Google Scholar Neil M. Wilson, Neil M. Wilson Search for other works by this author on: Oxford Academic PubMed Google Scholar John DiGiovanni, John DiGiovanni Search for other works by this author on: Oxford Academic PubMed Google Scholar Mont R. Juchau, Mont R. Juchau Search for other works by this author on: Oxford Academic PubMed Google Scholar James K. Selkirk James K. Selkirk Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 58, Issue 4, April 1977, Pages 1051–1055, https://doi.org/10.1093/jnci/58.4.1051 Published: 01 April 1977 Article history Received: 19 July 1976 Accepted: 14 October 1976 Published: 01 April 1977
Effect of Maintenance Tocolysis With Nifedipine in Threatened Preterm Labor on Perinatal Outcomes
Authors: Carolien Roos, Marc E. A. Spaanderman, Ewoud Schuit, Kitty W. M. Bloemenkamp, Antoinette C. Bolte, Jérôme Cornette, Johannes J. J. Duvekot, Jim van Eyck, Maureen T. M. Franssen, Christianne J. de Groot, Joke H. Kok, Anneke Kwee, Ashley Merién, Bas Nij Bijvank, Brent C. Opmeer, Martijn A. Oudijk, Mariëlle G. van Pampus, Dimitri N. M. Papatsonis, Martina M. Porath, Hubertina C. J. Scheepers, Sicco A. Scherjon, Krystyna M. Sollie, Sylvia M. C. Vijgen, Christine Willekes, Ben Willem J. Mol, Joris A. M. van der Post, Fred K. Lotgering, for the APOSTEL-II Study Group
Journal: JAMA (2013)

RETERM BIRTH IS THE MOST COMmon cause of neonatal morbidity and mortality worldwide.Almost 75% of perinatal deaths occur in infants born before 37 weeks' gestation. 1Consequently, pre-term birth is associated with a large burden of disease, high costs for medical care, special education, and institutionalized care for disabled infants. 2 In threatened preterm labor before 34 weeks, delay of delivery for 48 hours allows antenatal corticosteroid treatment to improve fetal maturity and transfer of the pregnant woman to a center with a neonatal intensive care unit. 3For initial tocolysis, nifedipine is comparable with magnesium sulfate 4 and superior to ritodrine 5 and atosiban. 6Because perinatal morbidity and
Conditional Regulatory T-Cell Depletion Releases Adaptive Immunity Preventing Carcinogenesis and Suppressing Established Tumor Growth
Authors: Michele W.L. Teng, Shin Foong Ngiow, Bianca von Scheidt, Nicole McLaughlin, Tim Sparwasser, Mark J. Smyth
Journal: Cancer Research (2010)

Foxp3 is a central control element in the development and function of regulatory T cells (Treg), and mice expressing a diphtheria toxin (DT) receptor-enhanced green fluorescent protein fusion protein under the control of the foxp3 gene locus (DEREG mice) allow conditional and efficient depletion of Foxp3(+) Treg by DT injection. Herein, we use DEREG mice and a mouse model of carcinogenesis to show that conditional and effective Treg depletion can both protect mice from carcinogenesis by innate control, yet permanently eradicate a proportion of de novo-established tumors in mice in a largely CD8(+) T-cell- and IFN-γ-dependent manner. Tumors displayed a heterogeneous response to Treg depletion, and suppression of established tumors was accompanied by an increase in the tumor-infiltrating CD8(+) T-cell/B-cell ratio. Tumor rejection occurred in the absence of overt autoimmunity, suggesting that effective transient Treg depletion strategies may be therapeutic in at least a proportion of spontaneous tumors developing in the host.
The Ludwig pattern of androgenetic alopecia is due to a hierarchy of androgen sensitivity within follicular units that leads to selective miniaturization and a reduction in the number of terminal hairs per follicular unit
Authors: A. Yazdabadi, J. Magee, S. Harrison, R. Sinclair
Journal: British Journal of Dermatology (2008)

Hair follicles exist within follicular units (FUs). In utero the central primary hair follicles are surrounded by smaller secondary follicles. Each FU is nourished by a single arborizing arrector pili muscle that attaches circumferentially around the primary follicle with variable attachment to other follicles. Androgenetic alopecia (AA) miniaturizes susceptible scalp hair follicles in a distinctive and reproducible fashion manifesting in different patterns between men and women.We hypothesized that there is an additional layer to the patterning in AA, with a hierarchy of susceptibility within FUs to AA, and that the diffuse hair loss seen in women with AA is due to a reduction in the number of terminal hairs per FU rather than uniform miniaturization of entire FUs.We compared the mean numbers of FUs and terminal hairs per FU in 4-mm scalp punch biopsies in 24 women with AA with those in 21 controls.There was no significant difference in the number of FUs; however, women with AA had 2.40 terminal hairs per FU compared with 3.38 in the control group (P=0.0001) associated with a mean increase of 0.6 vellus hairs per FU. Complete miniaturization of all hairs within the FU was not seen.Diffuse hair loss in women with AA is due to a reduction in the number of terminal hairs per FU and an increase in the number of vellus hairs. This supports the hypothesis of a hierarchy of susceptibility within FUs to AA. Further investigation is required to ascertain whether secondary and tertiary hair follicles are more susceptible than primary follicles.
Inflammation-associated Cell Cycle–independent Block of Apoptosis by Survivin in Terminally Differentiated Neutrophils
Authors: Frank Altznauer, Sibylla Martinelli, Shida Yousefi, Christine Thürig, Inès Schmid, Edward M. Conway, Martin H. Schöni, Peter Vogt, Christoph Mueller, Martin F. Fey, Uwe Zangemeister-Wittke, Hans-Uwe Simon
Journal: The Journal of Experimental Medicine (2004)

Survivin has received great attention due to its expression in many human tumors and its potential as a therapeutic target in cancer. Survivin expression has been described to be cell cycle–dependent and restricted to the G2-M checkpoint, where it inhibits apoptosis in proliferating cells. In agreement with this current view, we found that survivin expression was high in immature neutrophils, which proliferate during differentiation. In contrast with immature cells, mature neutrophils contained only little or no survivin protein. Strikingly, these cells reexpressed survivin upon granulocyte/macrophage colony-stimulating factor (CSF) or granulocyte CSF stimulation in vitro and under inflammatory conditions in vivo. Moreover, survivin-deficient mature neutrophils were unable to increase their lifespan after survival factor exposure. Together, our findings demonstrate the following: (a) overexpression of survivin occurs in primary, even terminally differentiated cells and is not restricted to proliferating cells; and (b) survivin acts as an inhibitor of apoptosis protein in a cell cycle–independent manner. Therefore, survivin plays distinct and independent roles in the maintenance of the G2-M checkpoint and in apoptosis control, and its overexpression is not restricted to proliferating cells. These data provide new insights into the regulation and function of survivin and have important implications for the pathogenesis, diagnosis, and treatment of inflammatory diseases and cancer.
Tracheobronchomegaly--the Mounier-Kuhn syndrome: report of two cases and review of the literature
Authors: J Van Schoor, G Joos, R Pauwels
Journal: European Respiratory Journal (1991)

Tracheobronchomegaly (TBM) is a rare disorder of uncertain aetiology, characterized by marked dilatation of the trachea and main bronchi, bronchiectasis and recurrent lower respiratory tract infections. Two patients with TBM are presented. In one case, a marked decrease of elastic and smooth muscle tissue was present in the bronchial biopsy specimens, obtained by rigid bronchoscopy. The airways of the second patient were visualized using computed tomography. The dimensions of the airways of our patients are compared with the normal values supplied in the literature.
Markers of circulating tumour cells in the peripheral blood of patients with melanoma correlate with disease recurrence and progression
Authors: A.L. Reid, M. Millward, R. Pearce, M. Lee, M.H. Frank, A. Ireland, L. Monshizadeh, T. Rai, P. Heenan, S. Medic, P. Kumarasinghe, M. Ziman
Journal: British Journal of Dermatology (2012)

Background Multimarker quantitative real‐time polymerase chain reaction (qRT‐PCR) represents an effective method for detecting circulating tumour cells in the peripheral blood of patients with melanoma. Objectives To investigate whether the phenotype of circulating melanoma cells represents a useful indicator of disease stage, recurrence and treatment efficacy. Methods Peripheral blood was collected from 230 patients with melanoma and 152 healthy controls over a period of 3 years and 9 months. Clinical data and blood samples were collected from patients with primary melanoma (early stages, 0–II, n = 154) and metastatic melanoma (late stages, III–IV, n = 76). Each specimen was examined by qRT‐PCR analysis for the expression of five markers: MLANA, ABCB5, TGFβ2, PAX3d and MCAM. Results In total, 212 of the patients with melanoma (92%) expressed markers in their peripheral blood. Two markers, MLANA and ABCB5, had the greatest prognostic value, and were identified as statistically significant among patients who experienced disease recurrence within our study period, being expressed in 45% (MLANA) and 49% (ABCB5) of patients with recurrence (P = 0·001 and P = 0·031, respectively). For patients administered nonsurgical treatments, MCAM expression correlated with poor treatment outcome. Conclusions Circulating tumour cells were detectable at all stages of disease and long after surgical treatment, even when patients were considered disease free. Specifically, expression of ABCB5 and MLANA had significant prognostic value in inferring disease recurrence, while MCAM expression was associated with poor patient outcome after treatment, confirming multimarker qRT‐PCR as a potential technique for monitoring disease status.
Proto-oncogene PBF/PTTG1IP Regulates Thyroid Cell Growth and Represses Radioiodide Treatment
Authors: Martin L. Read, Greg D. Lewy, Jim C.W. Fong, Neil Sharma, Robert I. Seed, Vicki E. Smith, Erica Gentilin, Adrian Warfield, Margaret C. Eggo, Jeffrey A. Knauf, Wendy E. Leadbeater, John C. Watkinson, Jayne A. Franklyn, Kristien Boelaert, Christopher J. McCabe
Journal: Cancer Research (2011)

Abstract Pituitary tumor transforming gene (PTTG)-binding factor (PBF or PTTG1IP) is a little characterized proto-oncogene that has been implicated in the etiology of breast and thyroid tumors. In this study, we created a murine transgenic model to target PBF expression to the thyroid gland (PBF-Tg mice) and found that these mice exhibited normal thyroid function, but a striking enlargement of the thyroid gland associated with hyperplastic and macrofollicular lesions. Expression of the sodium iodide symporter (NIS), a gene essential to the radioiodine ablation of thyroid hyperplasia, neoplasia, and metastasis, was also potently inhibited in PBF-Tg mice. Critically, iodide uptake was repressed in primary thyroid cultures from PBF-Tg mice, which could be rescued by PBF depletion. PBF-Tg thyroids exhibited upregulation of Akt and the TSH receptor (TSHR), each known regulators of thyrocyte proliferation, along with upregulation of the downstream proliferative marker cyclin D1. We extended and confirmed findings from the mouse model by examining PBF expression in human multinodular goiters (MNG), a hyperproliferative thyroid disorder, where PBF and TSHR was strongly upregulated relative to normal thyroid tissue. Furthermore, we showed that depleting PBF in human primary thyrocytes was sufficient to increase radioiodine uptake. Together, our findings indicate that overexpression of PBF causes thyroid cell proliferation, macrofollicular lesions, and hyperplasia, as well as repression of the critical therapeutic route for radioiodide uptake. Cancer Res; 71(19); 6153–64. ©2011 AACR.
Intensity of leisure-time physical activity and cancer mortality in men
Authors: J A Laukkanen, R Rauramaa, T H Mäkikallio, A T Toriola, S Kurl
Journal: British Journal of Sports Medicine (2009)

there is a lack of evidence to show the role of exercise intensity in the prevention of cancer mortality because no previous studies have shown this relation. The relationship of leisure-time physical activity with cancer mortality was therefore assessed.participants were from a population-based sample of 2560 men from eastern Finland with no history of cancer at baseline. Physical activity was assessed using the 12-month leisure-time physical activity questionnaire. During an average follow-up of 16.7 years, a total of 181 cancer related deaths occurred.an increase of 1.2 metabolic units (MET or metabolic equivalents of oxygen consumption; 1 SD in metabolic equivalents) in the mean intensity of leisure-time physical activity was related to a decrease (relative risk (RR) 0.85, 95% CI 0.72 to 0.99) in cancer mortality mainly due to lung and gastrointestinal cancers, after adjustment for age, examination year, alcohol consumption, smoking, body mass index and energy, fibre and fat intake. Men with leisure-time physical activity of more than 5.2 MET (highest quartile) had a lower (RR 0.63, 95% CI 0.40 to 0.99) cancer mortality compared with men whose mean intensity of physical activity was less than 3.7 MET (lowest quartile). The mean intensity of physical activity was related to the risk of cancer death among men who exercised at least 30 minutes per day on average.this prospective study indicates that the mean intensity of leisure-time physical activity is inversely associated with the risk of premature death from cancer in men.
A flow interruption device for measurement of airway resistance
Authors: PJ Chowienczyk, CP Lawson, S Lane, R Johnson, N Wilson, M Silverman, GM Cochrane
Journal: European Respiratory Journal (1991)

Unlike conventional methods, the interrupter method for measuring airway resistance is non-invasive and requires minimal patient co-operation. It can therefore be applied in critically ill patients, acute asthmatics, neonates, pre-school children, geriatric patients and unconscious patients. The method is based on transient interruption of airflow at the mouth for a brief period during which alveolar pressure equilibrates with mouth pressure. Measurement of mouth pressure is used to estimate alveolar pressure prior to interruption and the ratio of this to flow prior to interruption gives airway resistance. Using the interrupter method we have developed a portable device for measuring airway resistance which is simple to use and gives a direct instantaneous reading. Measurements of airway resistance obtained using the new device were compared with those obtained using conventional body plethysmograph methods in 43 adult patients. A close correlation was seen (r = 0.86). The two methods appear equally sensitive in detecting changes in airway resistance following bronchodilator therapy. The device has been used successfully in pre-school children unable to co-operate with conventional methods.