tbuckley/cabot-search huggingface dataset:
Variation in STAT4 is associated with systemic lupus erythematosus in a Finnish family cohort
Authors: A. Hellquist, J. K. Sandling, M. Zucchelli, S. Koskenmies, H. Julkunen, M. D'Amato, S. Garnier, A.-C. Syvanen, J. Kere
Journal: Annals of the Rheumatic Diseases (2009)

<h3>Objectives</h3> To investigate whether 10 single nucleotide polymorphisms (SNPs) and haplotypes in the <i>STAT4</i> gene, previously associated with systemic lupus erythematosus (SLE) in a Swedish case–control cohort, are also associated with SLE risk in a Finnish SLE family cohort. <h3>Method</h3> Genotyping was performed in 192 Finnish families, with 237 affected subjects and their healthy relatives, using the SNPstream genotyping system. <h3>Results</h3> Transmission disequilibrium test analysis provided the strongest signal of association for two linked SNPs: rs7582694 (p=0.002, OR=2.57) and rs10181656 (p=0.001, OR=2.53). Haplotype association analysis using a sliding window approach was also performed and showed that the strongest association signal originates from SNPs in intron 3 of <i>STAT4</i>. <h3>Conclusion</h3> The main association signal for <i>STAT4</i> with SLE previously reported in Caucasians is the same in the Finnish population. This is the first study that confirms the association of <i>STAT4</i> with SLE in a family cohort.
Progression of radiographic joint damage in rheumatoid arthritis: independence of erosions and joint space narrowing
Authors: J S Smolen, D M van der Heijde, D Aletaha, S Xu, J Han, D Baker, E W S. Clair
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objective:</h3> To compare the progression of erosions and joint space narrowing (JSN) in patients with early active rheumatoid arthritis (RA) using data obtained in the "Active-controlled Study of Patients receiving Infliximab for the treatment of Rheumatoid arthritis of Early onset" (ASPIRE) study. <h3>Methods:</h3> This was a post hoc analysis of patients in ASPIRE who received placebo plus methotrexate (MTX) or infliximab (3 or 6 mg/kg) plus MTX. Radiographs of the hands (870 patients) and feet (871 patients) were obtained at baseline and week 54 and scored using the van der Heijde/Sharp method. In total, 7160 joints in the placebo plus MTX group and 18 908 joints in the combined infliximab plus MTX group were included in this analysis. <h3>Results:</h3> At baseline, 83.4% of joints in the placebo plus MTX group had no radiographic damage, 8.5% had only erosions, 4.4% had only JSN and 3.7% had both. The distribution was similar in the infliximab plus MTX group. In the placebo plus MTX group, the majority of joints did not have development or progression of radiographic damage from baseline to week 54; among joints that did have development or progression of damage at week 54, erosions occurred more often than JSN. The same pattern was observed in the infliximab plus MTX group, although the proportions of joints with damage at week 54 were generally larger in the placebo plus MTX group. There was a tendency for joints with existing erosions or JSN to have progression of damage, rather than development of new damage. <h3>Conclusions:</h3> Erosions were the predominant type of damage observed in both treatment groups. Erosions and JSN are related but partly independent processes.
Insulin dependent diabetes mellitus: a lethal disease in the developing world
Authors: K G M M Alberti
Journal: BMJ (1994)

Before the discovery of insulin in 1921 the diagnosis of insulin dependent diabetes mellitus was tantamount to a death sentence, with 40% or more diabetic patients dying of ketoacidosis. This changed dramatically after 1921, with ketoacidosis becoming a minor cause of death. Life expectancy increased appreciably, although not to the extent hoped for because of the emergence of nephropathy and ischaemic heart disease.

Now, with improved treatment and prevention, life expectancy is good for a patient with newly diagnosed insulin dependent diabetes mellitus. Thus someone in whom the disease was diagnosed before the age of 17 in Pittsburgh between 1950 and 1981 had an 88% chance of surviving 20 years.1 Survival now would be even better, and the results of the recent diabetic control and complications trial give hope for further improvement.2

Sadly, this is not the situation worldwide. Insulin dependent diabetes mellitus is not only a disorder of developed countries: it occurs everywhere, although its incidence varies widely from about 2-4 per 100 000 in parts of sub-Saharan Africa3 to 14 per 100 000 in Britain. A substantial number of children are affected, and in …
Primary and secondary glioblastomas: From concept to clinical diagnosis
Authors: Paul Kleihues, Hiroko Ohgaki
Journal: Neuro-Oncology (1999)

Glioblastomas may develop de novo (primary glioblastomas) or through progression from low-grade or anaplastic astrocytomas (secondary glioblastomas). These subtypes of glioblastoma constitute distinct disease entities that evolve through different genetic pathways, affect patients at different ages, and are likely to differ in prognosis and response to therapy. Primary glioblastomas develop in older patients and typically show EGFR overexpression, PTEN (MMAC1) mutations, CDKN2A (p16) deletions, and less frequently, MDM2 amplification. Secondary glioblastomas develop in younger patients and often contain TP53 mutations as the earliest detectable alteration. These characteristics are derived largely from patients selected on the basis of clinical history and sequential biopsies. Currently available data are insufficient for a substitution of histologic classification and grading of astrocytic tumors by genetic typing alone. More subtypes of glioblastomas may exist with intermediate clinical and genetic profiles, a factor exemplified by the giant-cell glioblastoma that clinically and genetically occupies a hybrid position between primary (de novo) and secondary glioblastomas. Future research should aim at the identification of criteria for a combined clinical, histologic, and genetic classification of astrocytic tumors.
The JNK Pathway Regulates the In Vivo Deletion of Immature CD4+CD8+ Thymocytes
Authors: Mercedes Rincón, Alan Whitmarsh, Derek D. Yang, Linda Weiss, Benoit Dérijard, Prash Jayaraj, Roger J. Davis, Richard A. Flavell
Journal: The Journal of Experimental Medicine (1998)

The extracellular signal-regulated kinase (ERK), the c-Jun NH2-terminal kinase (JNK), and p38 MAP kinase pathways are triggered upon ligation of the antigen-specific T cell receptor (TCR). During the development of T cells in the thymus, the ERK pathway is required for differentiation of CD4(-)CD8(-) into CD4(+)CD8(+) double positive (DP) thymocytes, positive selection of DP cells, and their maturation into CD4(+) cells. However, the ERK pathway is not required for negative selection. Here, we show that JNK is activated in DP thymocytes in vivo in response to signals that initiate negative selection. The activation of JNK in these cells appears to be mediated by the MAP kinase kinase MKK7 since high levels of MKK7 and low levels of Sek-1/MKK4 gene expression were detected in thymocytes. Using dominant negative JNK transgenic mice, we show that inhibition of the JNK pathway reduces the in vivo deletion of DP thymocytes. In addition, the increased resistance of DP thymocytes to cell death in these mice produces an accelerated reconstitution of normal thymic populations upon in vivo DP elimination. Together, these data indicate that the JNK pathway contributes to the deletion of DP thymocytes by apoptosis in response to TCR-derived and other thymic environment- mediated signals.
Extrusion of pyrophosphate into extracellular media by osteoarthritic cartilage incubates.
Authors: D S Howell, O Muniz, J C Pita, J E Enis
Journal: Journal of Clinical Investigation (1975)

The distribution of calcium pyrophosphate mineral phase, almost exclusively confined to articular cartilage in chondrocalcinosis, and the high level of pyrophosphate (PPi) ion relative to serum in synovial fluid in patients with either chondrocalcinosis or advanced osteoarthritis led to an investigation of whether cartilage cells elaborate PPi ions. Incubates of articular cartilage from young rabbits but not from mature rabbits, as well as growth plates cartilage, released PPi into incubation media during a 4h period. Control rabbit ear cartilage and synovial membrane elaborated negligible amounts of PPi. The PPi was shown to be undialyzable but could be dissociated from the alkaline phosphatase by ultracentrifugation. In 16 patients with osteoarthritis, a substantial output of PPi by samples of articular cartilage from the knee was demonstrated. It is postulated that either rapid cell division and matrix synthesis found in the base of ulcerating osteoarthritic cartilage or remodeling calcified sites are the source of the PPi in such osteoarthritic cartilage. It is further hypothesized that this PPi output accounts at least in part for the elevated PPi levels found in synovial fluid of patients with osteoarthritis.
Challenges moving forward with economic evaluations of exercise intervention strategies aimed at combating cognitive impairment and dementia
Authors: Jennifer C Davis, Ging-Yuek R Hsiung, Teresa Liu-Ambrose
Journal: British Journal of Sports Medicine (2011)

Cognitive decline among adults aged 65 years and older is a substantial public health problem in terms of incidence, health burden to the individual and care givers, as well as healthcare-related costs.1 With the world's ageing population increasing, the number of older adults with dementia is estimated to rise from 26.6 million in 2007 to 106.2 million in 2050.2

The economic burden of cognitive impairment and dementia cannot be ignored. In 2000, dementia was the third most costly health condition to care for in the USA, with annual costs estimated at $100 billion (in 1997 US prices). Another study calculated that the mean annual cost for dementia care is €28 000 per patient.3 The direct costs in the UK of Alzheimer's disease were estimated at £23 billion annually.4 Clearly, the cost of care for dementia is extremely high, and any strategies that delay the onset and/or slow the progression of cognitive decline and dementia can have enormous societal return in terms of costs and consequences. To date, effective pharmacotherapy for cognitive decline remains a challenge.1 Rather, recent evidence emphasises the importance of behavioural strategies such as physical activity to promote cognitive function.5,–,10 Specifically, results from randomised controlled trials suggest that exercise has benefits for cognitive function among cognitively normal older adults5,–,7 and among older adults with mild cognitive impairment.8 9 However, more research is needed to ascertain the direct effect of exercise on cognition among those with dementia, such as Alzheimer's disease and vascular dementia. Nevertheless, as previously highlighted by Erickson and Kramer,10 physical activity provides clear benefits for cognition among seniors. These neuroscientists contend that ‘physical activity is an inexpensive treatment that could have substantial preventive and restorative properties for cognitive and …
Nosocomial Gram-negative Bacillary Parotitis
Authors: Timothy L. Pruett, Richard L. Simmons
Journal: JAMA (1984)

Historically, Staphylococcus aureus has been the primary pathogen in acute suppurative parotitis (ASP). This report presents an index case of Pseudomonas aeruginosa bacteremia associated with ASP and an institutional review of parotitis in which three of 23 additional cases of pyogenic parotitis had enteric bacilli cultured either alone or as the primary pathogen. These cases support the previously undocumented supposition that enteric gram-negative bacilli and pseudomonads can be pathogens in ASP.
Quetiapine and rivastigmine and cognitive decline in Alzheimer's disease: randomised double blind placebo controlled trial
Authors: Clive Ballard, Marisa Margallo-Lana, Edmund Juszczak, Simon Douglas, Alan Swann, Alan Thomas, John O'Brien, Anna Everratt, Stuart Sadler, Clare Maddison, Lesley Lee, Carol Bannister, Ruth Elvish, Robin Jacoby
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objectives</b> To determine the respective efficacy of quetiapine and rivastigmine for agitation in people with dementia in institutional care and to evaluate these treatments with respect to change in cognitive performance. <b>Design</b> Randomised double blind (clinician, patient, outcomes assessor) placebo controlled trial. <b>Setting</b> Care facilities in the north east of England. <b>Participants</b> 93 patients with Alzheimer9s disease, dementia, and clinically significant agitation. <b>Intervention</b> Atypical antipsychotic (quetiapine), cholinesterase inhibitor (rivastigmine), or placebo (double dummy). <b>Main outcome measures</b> Agitation (Cohen-Mansfield agitation inventory) and cognition (severe impairment battery) at baseline and at six weeks and 26 weeks. The primary outcome was agitation inventory at six weeks. <b>Results</b> 31 patients were randomised to each group, and 80 (86%) started treatment (25 rivastigmine, 26 quetiapine, 29 placebo), of whom 71 (89%) tolerated the maximum protocol dose (22 rivastigmine, 23 quetiapine, 26 placebo). Compared with placebo, neither group showed significant differences in improvement on the agitation inventory either at six weeks or 26 weeks. Fifty six patients scored &gt; 10 on the severe impairment battery at baseline, 46 (82%) of whom were included in the analysis at six week follow up (14 rivastigmine, 14 quetiapine, 18 placebo). For quetiapine the change in severe impairment battery score from baseline was estimated as an average of -14.6 points (95% confidence interval -25.3 to -4.0) lower (that is, worse) than in the placebo group at six weeks (P = 0.009) and -15.4 points (-27.0 to -3.8) lower at 26 weeks (P = 0.01). The corresponding changes with rivastigmine were -3.5 points (-13.1 to 6.2) lower at six weeks (P = 0.5) and -7.5 points (-21.0 to 6.0) lower at 26 weeks (P = 0.3). <b>Conclusions</b> Neither quetiapine nor rivastigmine are effective in the treatment of agitation in people with dementia in institutional care. Compared with placebo, quetiapine is associated with significantly greater cognitive decline.
Applicability and prognostic value of histologic scoring systems in primary sclerosing cholangitis
Authors: Elisabeth M.G. de Vries, Joanne Verheij, Stefan G. Hubscher, Mariska M.G. Leeflang, Kirsten Boonstra, Ulrich Beuers, Cyriel Y. Ponsioen
Journal: Journal of Hepatology (2015)
Profiling of coexpression of multiple immune checkpoints in the CD4+ and CD8+ T cell components of the clear cell renal cell carcinoma immune infiltrate
Authors: Anne Monette, Nadia Al-Banna, Jean-Pierre Routy, Réjean Lapointe
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Immune checkpoint blockade therapies have been proven to elicit clinical responses in clear cell renal cell carcinoma (ccRCC) patients. A comprehensive profiling of the tumor landscape is however still required and will help to explain how for this cancer, the high densities of
Geographical variation in the prevalence of positive skin tests to environmental aeroallergens in the European Community Respiratory Health Survey I
Authors: P.‐J. Bousquet, S. Chinn, C. Janson, M. Kogevinas, P. Burney, D. Jarvis
Journal: Allergy (2007)

Background: Many studies have reported the prevalence of sensitization using skin prick tests. However, comparisons between studies and between regions are difficult because the number and the type of allergens tested vary widely. Using the European Community Health Respiratory Survey I data, the geographical variation of sensitization to environmental allergen as measured by skin tests was established. Methods: Adults aged 20–44 years, living in 35 centres in 15 developed countries, underwent skin tests for allergy to nine common aeroallergens: Dermatophagoides pteronyssinus , timothy grass, cat, Cladosporium herbarium , Alternaria alternata , birch, Olea europea , common ragweed and Parietaria judaica . The age–sex standardized prevalence of sensitization was determined and centres with high (95% confidence interval above and excluding study median) and low prevalence (95% confidence interval below and excluding study median) of sensitization to each allergen and to any of the nine allergens were identified. Results: There was substantial geographical variation in the prevalence of sensitization to each of the nine allergens tested and in the prevalence of sensitization to any allergen (lowest 17.1%, median 36.8% and highest 54.8%). Sensitization to D. pteronyssinus , grass pollen and cat were usually the most prevalent (median between centre 21.7%, 16.9% and 8.8%, respectively). Timothy grass sensitization was higher than that for any other pollen species. Conclusions: As expected, geographical variations of sensitization to environmental allergen were observed across centres. These findings were compatible for those observed with serum‐specific IgE. Skin tests can be used to assess the geographical distribution of allergens in a multicentric epidemiological survey.
Influence of seasonal variations in ambient temperatures on performance of immunochemical faecal occult blood test for colorectal cancer screening: observational study from the Florence district
Authors: G. Grazzini, L. Ventura, M. Zappa, S. Ciatto, M. Confortini, S. Rapi, T. Rubeca, C. B. Visioli, S. P. Halloran
Journal: Gut (2010)

Faecal occult blood testing (FOBT) in population screening has proved to be effective in reducing mortality from colorectal cancer. In Italy a latex agglutination FOBT has been adopted for a single-sample screening programme. The aim of this study was to examine the performance of FOBTs in the Florence screening programme over several seasons to evaluate the impact of variations in ambient temperature on the performance of the screening test.Measured haemoglobin (Hb) concentrations were aggregated into seasons with their average ambient temperature (AAT). Using logistic regression, the AAT over the period preceding the test measurement was analysed. This period included the time between faecal sampling and return of the test sample (mean 7days) and the time in the laboratory refrigerator before analysis (mean 4days). The AAT from days 5-11 before analysis of the test sample was considered a determinant of test positivity. The Kruskal-Wallis rank test was used to evaluate the significance of seasonal and/or AAT-related differences in Hb concentration. A logistic regression model adjusted for sex, age, season and screening episode (first or repeated examination) was constructed.199 654 FOBT results were examined. Mean FOBT seasonal Hb concentrations (ng/ml) were: spring 27.6 (95% CI 26.2 to 29.1); summer 25.2 (95% CI 23.1 to 27.3); autumn 29.2 (95% CI 27.7 to 30.6); winter 29.5 (95% CI 27.9 to 31.1). Logistic regression showed that there was a 17% lower probability of the FOBT being positive in summer than in winter. The results of the logistic regression showed that an increase in temperature of 1°C produced a 0.7% reduction in probability of a FOBT being positive. In the summer the probability of detecting a cancer or an advanced adenoma was about 13% lower than in the winter.This study showed that there is a significant fall in Hb concentration at higher ambient temperatures. These results will have important implications for the organisation of immunochemical FOBT-based screening programmes, particularly in countries with high ambient temperatures.
A Patient With Kartagener and Paterson-Brown-Kelly Syndromes
Authors: N. Wendell Todd
Journal: JAMA (1975)

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S-Nitrosylation of parkin as a novel regulator of p53-mediated neuronal cell death in sporadic Parkinson’s disease
Authors: Carmen R Sunico, Tomohiro Nakamura, Edward Rockenstein, Michael Mante, Anthony Adame, Shing Fai Chan, Traci Fang Newmeyer, Eliezer Masliah, Nobuki Nakanishi, Stuart A Lipton
Journal: Molecular Neurodegeneration (2013)

Abstract Background Mutations in the gene encoding parkin, a neuroprotective protein with dual functions as an E3 ubiquitin ligase and transcriptional repressor of p53, are linked to familial forms of Parkinson’s disease (PD). We hypothesized that oxidative posttranslational modification of parkin by environmental toxins may contribute to sporadic PD. Results We first demonstrated that S-nitrosylation of parkin decreased its activity as a repressor of p53 gene expression, leading to upregulation of p53. Chromatin immunoprecipitation as well as gel-shift assays showed that parkin bound to the p53 promoter, and this binding was inhibited by S-nitrosylation of parkin. Additionally, nitrosative stress induced apoptosis in cells expressing parkin, and this death was, at least in part, dependent upon p53. In primary mesencephalic cultures, pesticide-induced apoptosis was prevented by inhibition of nitric oxide synthase (NOS). In a mouse model of pesticide-induced PD, both S-nitrosylated (SNO-)parkin and p53 protein levels were increased, while administration of a NOS inhibitor mitigated neuronal death in these mice. Moreover, the levels of SNO-parkin and p53 were simultaneously elevated in postmortem human PD brain compared to controls. Conclusions Taken together, our data indicate that S-nitrosylation of parkin, leading to p53-mediated neuronal cell death, contributes to the pathophysiology of sporadic PD.
Penile intraepithelial neoplasia: clinical spectrum and treatment of 35 cases
Authors: W.M. Porter, N. Francis, D. Hawkins, M. Dinneen, C.B. Bunker
Journal: British Journal of Dermatology (2002)

Penile intraepithelial neoplasia (PIN) is the term used to describe erythroplasia of Queyrat (EQ), Bowen's disease (BD) and bowenoid papulosis (BP). These conditions are distinct clinical entities and have different epidemiological and aetiological associations and prognostic implications.To describe the presentation and treatment of patients with PIN.Thirty-five patients presenting with PIN over a 7-year period are described.Our observations include: (i) patients with BP are younger than those with EQ or BD and sometimes have a history of immunosuppression; (ii) patients with BP usually have a history or clinical evidence of previous genital human papillomavirus infection; (iii) patients with EQ often have a concurrent penile dermatosis (lichen sclerosus or lichen planus); (iv) patients with PIN are usually uncircumcised; and (v) response to treatment of BP depends on the integrity of the immune system.We recommend vigorous treatment of all patients with PIN, including circumcision. Smoking should be actively discouraged. Patients should have life-long follow-up and partners of patients with BP should be screened for other forms of intraepithelial neoplasia (cervical and anal).