tbuckley/cabot-search huggingface dataset:
Randomised controlled trial of interferon alfa 2A (rbe) (Roferon-A) for the treatment of chronic hepatitis B virus (HBV) infection: factors that influence response.
Authors: M G Brook, J A McDonald, P Karayiannis, L Caruso, G Forster, J R Harris, H C Thomas
Journal: Gut (1989)

In a randomised controlled trial recombinant interferon alpha 2A (Roferon-A, rIFN alfa A) given at a dosage of 10 million units (MU)/m2 thrice weekly for six months was significantly better (p less than 0.02) than no treatment in producing a sustained loss of hepatitis Be antigen (HBeAg) in hepatitis B virus (HBV) chronic carriers. Although lower doses (5 MU/m2 and 2.5 MU/m2) also produced some responses, the seroconversion rate was not significantly greater than that observed in the control group. Sixteen of the 45 patients receiving interferon were human immunodeficiency virus (HIV) antibody positive: none of these responded. Forty one per cent of the anti-HIV negative patients receiving interferon (12/29, p less than 0.005) lost HBeAg and 17% (5/29) lost hepatitis B surface antigen (HBsAg). The response rate among these anti-HIV negative patients receiving at least three months therapy was 46% and 19% respectively. Low pretreatment HBV-DNA and absence of anti-HIV were the only significant independent variables predicting response to therapy (p less than 0.03 and p less than 0.05 respectively). In six patients, neutralising antibodies to alpha interferon were detected during therapy, the majority being non-responders.
Gene Expression Alterations in Immune System Pathways in the Thymus after Exposure to Immunosuppressive Chemicals
Authors: Rachel Frawley, Kimber White, Ronnetta Brown, Deborah Musgrove, Nigel Walker, Dori Germolec
Journal: Environmental Health Perspectives (2010)

Dysregulation of positive and negative selection, antigen presentation, or apoptosis in the thymus can lead to immunosuppression or autoimmunity. Diethylstilbestrol (DES), dexamethasone (DEX), cyclophosphamide (CPS), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are immunosuppressive chemicals that induce similar immunotoxic effects in the thymus, however, the mechanism of toxicity is purported to be different for each compound.We hypothesized that genomic analysis of thymus after chemical-induced atrophy would yield transcriptional profiles that suggest pathways of toxicity associated with reduced function.Female B6C3F1 mice were exposed to these immunosuppressive agents and changes in gene expression and immune cell subpopulations were evaluated.All four chemicals induced thymic atrophy and changes in both the relative proportion and absolute number of CD3(+), CD4(+)/CD8(-), CD4(-)/CD8(+), and CD4(+)/CD8(+) thymocytes. The most significant impact of exposure to DEX, DES, and CPS was modulation of gene expression in the T-cell receptor (TCR) complex and TCR and CD28 signaling pathways; this could represent a common mechanism of action and play a pivotal role in lineage commitment and development of T cells. Up-regulation of genes associated with the antigen presentation and dendritic cell maturation pathways was the most distinctive effect of TCDD exposure. These elements, which were also up-regulated by DEX and DES, contribute to positive and negative selection.Genomic analysis revealed gene expression changes in several pathways that are commonly associated with xenobiotic-induced immune system perturbations, particularly those that contribute to the development and maturation of thymic T cells.
Distribution of total serum IgE and specific IgE to common aeroallergens by sex and age, and their relationship to each other in a random sample of the Dutch general population aged 20–70 years*
Authors: M. Kerkhof, J. H. J. Droste, J. G. R. de Monchy, J. P. Schouten, B. Rijcken
Journal: Allergy (1996)

To describe the distribution of serum total IgE and specific IgE. to common aeroallergens by sex and age and to study their relationship to each other, we measured serum total IgE and specific IgE (CAP) to house‐dust mite, timothy grass, cat, birch, and Cladosporium in a random sample of 2496 subjects, aged 20–70 years from the Dutch general population. We found that total IgE was higher in men, independently of smoking, and that total IgE had no relationship with age after adjustment for specific IgE and smoking in linear regression analysis. At least one positive specific IgE test was found in 32% in both sexes. Men had higher prevalences of specific IgE to house‐dust mite and lower prevalences of specific IgE to birch than women. The proportion with positive specific IgE decreased with age. The mean total IgE increased with the number of positive specific IgE tests. Thus, total IgE is higher in men and has no relationship with age if specific IgE is taken into account. The prevalences of specific IgE to aeroallergens are high and decrease with increasing age. We suggest that sex differences in total IgE should be considered when using total IgE.
Changing patterns of communicable disease in England and Wales. Part i--Newly recognised diseases.
Authors: N S Galbraith, P Forbes, R T Mayon-White
Journal: BMJ (1980)

Campylobacter enteritis, giardiasis, legionnaires' disease, primary amoebic meningoencephalitis, and the viral haemorr- hagic fevers are among the "new" diseases.In hospitals group B streptococcal infections have been recognised, there have been episodes of hospital-acquired enterovirus infections, and developments in surgical prostheses and immunosuppression have been followed by the appearance of new infections due to low-grade opportunistic pathogens. Campylobacter enteritisUntil the 1970s Campylobacter spp were regarded as vibrios that caused diarrhoea in cattle and other animals and rare bacteraemic infections in man.Following the recognition that C jejuni/coli (C fetus subsp jejuni) causes human diarrhoeal disease' and the development of simple laboratory methods for identification2 this organism has become the commonest pathogen isolated from the faeces of patients with sporadic acute diarrhoeal illness (about 50% of such patients).Two hundred new cases are now reported to the Communicable Disease Surveillance Centre (CDSC) each week.As routine investigations do not show a microbial cause for most sporadic episodes
Psoriasis exacerbated by hypoparathyroidism with hypocalcaemia
Authors: GUNVER RISUM
Journal: British Journal of Dermatology (1973)

Journal Article Psoriasis exacerbated by hypoparathyroidism with hypocalcæmia Get access GUNVER RISUM GUNVER RISUM Department of Dermatology, The Finseninstitute, Copenhagen, Denmark Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 89, Issue 3, 1 September 1973, Pages 309–312, https://doi.org/10.1111/j.1365-2133.1973.tb02980.x Published: 01 September 1973 Article history Accepted: 01 March 1973 Published: 01 September 1973
Imaging: Strategies, Controversies, and Opportunities
Authors: Ronald Blasberg, David Piwnica-Worms
Journal: Clinical Cancer Research (2012)

Abstract At a Clinical and Translational Cancer Research Think Tank meeting sponsored by the American Association for Cancer Research in 2010, one of the breakout groups focused on new technologies and imaging. The discussions emphasized new opportunities in translational imaging and its role in the future, rather than established techniques that are currently in clinical practice. New imaging methods under development are changing the approach of imaging science from a focus on the anatomic description of disease to a focus on the molecular basis of disease. Broadly referred to as molecular imaging, these new strategies directly embrace the incorporation of cell and molecular biology concepts and techniques into image generation and can involve the introduction of genes into cells with the explicit intent to image the end products of gene expression with external imaging devices. These new methods hold the promise of providing clinicians with (i) robust linkages between cell and animal models and clinical trials, (ii) in vivo biomarkers that can be measured repeatedly and sequentially over time to observe dynamic disease processes and responses to treatment, and (iii) tools for preselection and patient population enrichment in phase II and III trials to improve outcomes and better direct treatment. These strategies provide real-time pharmacodynamic parameters and can be powerful tools to monitor therapeutic effects in a spatially and tissue-specific manner, which may reduce cost during drug development, because pharmacodynamic studies in animals can inform clinical trials and accelerate the translation process. The Imaging Response Assessment Team (IRAT) program serves as an example of how imaging techniques can be incorporated into clinical trials. IRATs work to advance the role of imaging in assessment of response to therapy and to increase the application of quantitative anatomic, functional, and molecular imaging endpoints in clinical trials, and imaging strategies that will lead to individualized patient care. Clin Cancer Res; 18(3); 631–7. ©2012 AACR.
Fibroblastic rheumatism: a Scandinavian case report
Authors: J K Pedersen
Journal: Annals of the Rheumatic Diseases (2004)

No patient had a history of a male twin or a solid organ transplant at the time of biopsy.SLE, systemic lupus erythematosus; CLE, cutaneous lupus erythematosus; DM, dermatomyositis; MF, mycosis fungoides.
Local Shear Stress and Brachial Artery Functions in End-Stage Renal Disease
Authors: Francis H. Verbeke, Mohsen Agharazii, Pierre Boutouyrie, Bruno Pannier, Alain P. Guérin, Gérard M. London
Journal: Journal of the American Society of Nephrology (2007)

Physiologic laminar shear stress (SS) is crucial for normal vascular structure and function. As a result of anemia-related lower whole-blood viscosity (WBV), SS could be reduced in patients with ESRD and might be associated with arterial functional alterations. In 44 patients with ESRD and 25 control subjects, brachial artery (BA) compliance and BA diameter changes (flow-mediated dilation [FMD[) were evaluated in response to local shear rate and SS changes during hand warming-induced hyperemia. Patients with ESRD and control subjects had similar BA blood flow, but SS was lower in patients with ESRD (P < 0.001), with lower shear rate (P < 0.01) and lower WBV (P < 0.0001). In control subjects, SS was positively (and physiologically) correlated with arterial diameter (P < 0.001). In contrast, in patients with ESRD, larger arterial diameter was associated with low SS (P < 0.05) and increased arterial wall elastic modulus (P < 0.001). Anemia-associated low WBV aggravates low shear rate, further contributing to SS reduction. These abnormalities were associated with decreased vasodilating response to endothelial mechanical stimulation. Compared with control subjects, BA compliance and FMD increases in response to hand warming-induced increased SS were lower in ESRD patients (P < 0.01), whereas their BA diameter response to glyceryl trinitrate did not differ. The long-term WBV and SS increases after anemia correction improved FMD (P < 0.01) and BA compliance (P < 0.05) and heightened arterial wall sensitivity to mechanical stimulation. Maintenance low SS as a result of anemia could play an indirect role in arterial dysfunction in patients with ESRD.
Progressive Tumor Formation in Mice with Conditional Deletion of TGF-β Signaling in Head and Neck Epithelia Is Associated with Activation of the PI3K/Akt Pathway
Authors: Yansong Bian, Anita Terse, Juan Du, Bradford Hall, Alfredo Molinolo, Pin Zhang, Wanjun Chen, Kathleen C. Flanders, J. Silvio Gutkind, Lalage M. Wakefield, Ashok B. Kulkarni
Journal: Cancer Research (2009)

Abstract The precise role of transforming growth factor (TGF)-β signaling in head and neck squamous cell carcinoma (SCC) is not yet fully understood. Here, we report generation of an inducible head- and neck-specific knockout mouse model by crossing TGF-β receptor I (Tgfbr1) floxed mice with K14-CreERtam mice. By applying tamoxifen to oral cavity of the mouse to induce Cre expression, we were able to conditionally delete Tgfbr1 in the mouse head and neck epithelia. On tumor induction with 7,12-dimethylbenz(a)anthracene (DMBA), 45% of Tgfbr1 conditional knockout (cKO) mice (n = 42) developed SCCs in the head and neck area starting from 16 weeks after treatment. However, no tumors were observed in the control littermates. A molecular analysis revealed an enhanced proliferation and loss of apoptosis in the basal layer of the head and neck epithelia of Tgfbr1 cKO mice 4 weeks after tamoxifen and DMBA treatment. The most notable finding of our study is that the phosphoinositide 3-kinase (PI3K)/Akt pathway was activated in SCCs that developed in the Tgfbr1 cKO mice on inactivation of TGF-β signaling through Smad2/3 and DMBA treatment. These observations suggest that activation of Smad-independent pathways may contribute cooperatively with inactivation of Smad-dependent pathways to promote head and neck carcinogenesis in these mice. Our results revealed the critical role of the TGF-β signaling pathway and its cross-talk with the PI3K/Akt pathway in suppressing head and neck carcinogenesis. [Cancer Res 2009;69(14):5918–26]
1284 CIRRHOSIS DEVELOPMENT ASSOCIATED WITH ELEVATED SERUM IGG4 IN TYPE I AUTOIMMUNE HEPATITIS
Authors: K. Abe, F. Katsushima, K. Monoe, Y. Kanno, H. Saito, A. Takahashi, J. Yokokawa, M. Seike, O. Yokosuka, M. Sata, H. Ohira
Journal: Journal of Hepatology (2011)
Understanding the Associations Between Statewide Diabetes Prevalence and Air Pollution Emissions
Authors: Elia B. Marquez, Benjamin R. Diaz, Patrick L. Gurian
Journal: Diabetes Care (2004)

In a recent letter in Diabetes Care , Lockwood (1) presented a statistically significant correlation between statewide diabetes prevalence and statewide total air pollution emissions reported in the Environmental Protection Agency’s (EPA) toxic release inventory (TRI) database ( r = 0.54, P < 0.0001). Lockwood noted that such a correlation does not necessarily result from a causal relationship, but called for further research into understanding the association between air pollution and diabetes. In response, Nicolich (2) took issue with Lockwood’s use of statewide data. To demonstrate that correlations based on statewide data may not show causal relationships, Nicolich presented four highly statistically significant correlations between statewide diabetes prevalence and factors that would not be expected to be causal factors in diabetes: latitude of the state capital, longitude of the state capital, state population, and numerical position of the state name on an alphabetized …
Cost-effectiveness of Bone Densitometry Followed by Treatment of Osteoporosis in Older Men
Authors: John T. Schousboe, Brent C. Taylor, Howard A. Fink, Robert L. Kane, Steven R. Cummings, Eric S. Orwoll, L. Joseph Melton, Douglas C. Bauer, Kristine E. Ensrud
Journal: JAMA (2007)

Osteoporotic fractures are common among elderly men.To evaluate among older men the cost-effectiveness of bone densitometry followed by 5 years of oral bisphosphonate therapy to prevent fractures for those found to have osteoporosis (femoral neck T score < or =-2.5), compared with no intervention.Computer Markov microsimulation model using a societal perspective and a lifetime horizon. Simulations were performed for hypothetical cohorts of white men aged 65, 70, 75, 80, or 85 years, with or without prior clinical fracture. Data sources for model parameters included the Rochester Epidemiology Project for fracture costs and population-based age-specific fracture rates; the Osteoporotic Fractures in Men (MrOS) study and published meta-analyses for the associations among prior fractures, bone density, and incident fractures; and published studies of fracture disutility.Costs per quality-adjusted life-year (QALY) gained for the densitometry and follow-up treatment strategy compared with no intervention, calculated from lifetime costs and accumulated QALYs for each strategy.Lifetime costs per QALY gained for the densitometry and follow-up treatment strategy were less than $50,000 for men aged 65 years or older with a prior clinical fracture and for men aged 80 years or older without a prior fracture. These results were most sensitive to oral bisphosphonate cost and fracture reduction efficacy, the strength of association between bone mineral density and fractures, fracture rates and disutility, and medication adherence.Bone densitometry followed by bisphosphonate therapy for those with osteoporosis may be cost-effective for men aged 65 years or older with a self-reported prior clinical fracture and for men aged 80 to 85 years with no prior fracture. This strategy may also be cost-effective for men as young as 70 years without a prior clinical fracture if oral bisphosphonate costs are less than $500 per year or if the societal willingness to pay per QALY gained is $100,000.
Chronic Hypoxia–Induced Upregulation of Store-Operated and Receptor-Operated Ca <sup>2+</sup> Channels in Pulmonary Arterial Smooth Muscle Cells
Authors: Mo-Jun Lin, George P.H. Leung, Wei-Min Zhang, Xiao-Ru Yang, Kay-Pong Yip, Chung-Ming Tse, James S.K. Sham
Journal: Circulation Research (2004)

Chronic hypoxic pulmonary hypertension is associated with profound vascular remodeling and alterations in Ca 2+ homeostasis in pulmonary arterial smooth muscle cells (PASMCs). Recent studies show that transient receptor potential (TRPC) genes, which encode store-operated and receptor-operated cation channels, play important roles in Ca 2+ regulation and cell proliferation. However, the influence of chronic hypoxia on TRPC channels has not been determined. Here we compared TRPC expression, and store- and receptor-operated Ca 2+ entries in PASMCs of normoxic and chronic hypoxic rats. Reverse-transcription polymerase chain reaction (RT-PCR), Western blot, and immunostaining showed consistently that TRPC1, TRPC3, and TRPC6 were expressed in intralobar pulmonary arteries (PAs) and PASMCs. Application of 1-oleoyl-2-acetyl-sn-glycerol (OAG) to directly activate receptor-operated channels, or thapsigargin to deplete Ca 2+ stores, caused dramatic increase in cation entry measured by Mn 2+ quenching of fura-2 and by Ca 2+ transients. OAG-induced responses were ≈700-fold more resistant to La 3+ inhibition than thapsigargin-induced responses. siRNA knockdown of TRPC1 and TRPC6 specifically attenuated thapsigargin- and OAG-induced cation entries, respectively, indicating that TRPC1 mediates store-operated entry and TRPC6 mediates receptor-operated entry. In hypoxic PAs, there were 2- to 3-fold increases in TRPC1 and TRPC6 expression. They were accompanied by significant increases in basal, OAG-induced, and thapsigargin-induced cation entries in hypoxic PASMCs. Moreover, removal of Ca 2+ or inhibition of store-operated Ca 2+ entry with La 3+ and SK&amp;F-96365 reversed the elevated basal [Ca 2+ ] i in PASMCs and vascular tone in PAs of chronic hypoxic animals, but nifedipine had minimal effects. Our results for the first time to our knowledge show that both store- and receptor-operated channels of PASMCs are upregulated by chronic hypoxia and contribute to the enhanced vascular tone in hypoxic pulmonary hypertension.
HCV genotype 2 as a risk factor for reactivation of chronic HCV infection
Authors: N Coppola
Journal: Gut (2005)

Little information is available in the literature on acute exacerbation of chronic hepatitis C (r-CHC).1–5 In Taiwan, Sheen et al estimated an annual incidence rate of 11.9%.3 In this study, 40.2% of 78 patients experienced at least one episode of reactivation during a mean observation period of six years and a total of 151 episodes of reactivation were observed, 45% of them symptomatic. The paper by Rumi et al from Milan ( Gut 2005; 54 :402–6) on r-CHC in relation to hepatitis C virus (HCV) genotyping described it as frequent in patients with genotype 2c (39% of 100 patients) and infrequent in those with genotype 1b (7.5% of 106 patients), with a rate×1000 persons/year of 55.6 and 15.0, respectively. From January 2002 to the …
Survivin Loss in Thymocytes Triggers p53-mediated Growth Arrest and p53-independent Cell Death
Authors: Hitoshi Okada, Chris Bakal, Arda Shahinian, Andrew Elia, Andrew Wakeham, Woong-Kyung Suh, Gordon S. Duncan, Maria Ciofani, Robert Rottapel, Juan Carlos Zúñiga-Pflücker, Tak W. Mak
Journal: The Journal of Experimental Medicine (2004)

Because survivin-null embryos die at an early embryonic stage, the role of survivin in thymocyte development is unknown. We have investigated the role by deleting the survivin gene only in the T lineage and show here that loss of survivin blocks the transition from CD4− CD8− double negative (DN) thymocytes to CD4+ CD8+ double positive cells. Although the pre–T cell receptor signaling pathway is intact in survivin-deficient thymocytes, the cells cannot respond to its signals. In response to proliferative stimuli, cycling survivin-deficient DN cells exhibit cell cycle arrest, a spindle formation defect, and increased cell death. Strikingly, loss of survivin activates the tumor suppressor p53. However, the developmental defects caused by survivin deficiency cannot be rescued by p53 inactivation or introduction of Bcl-2. These lines of evidence indicate that developing thymocytes depend on the cytoprotective function of survivin and that this function is tightly coupled to cell proliferation but independent of p53 and Bcl-2. Thus, survivin plays a critical role in early thymocyte development.