tbuckley/cabot-search huggingface dataset:
Lupus Nephritis: Glycogen Synthase Kinase 3β Promotion of Renal Damage Through Activation of the NLRP3 Inflammasome in Lupus‐Prone Mice
Authors: Jijun Zhao, Hongyue Wang, Yuefang Huang, Hui Zhang, Shuang Wang, Felicia Gaskin, Niansheng Yang, Shu Man Fu
Journal: Arthritis & Rheumatology (2014)

Objective Glycogen synthase kinase 3β (GSK‐3β) has been demonstrated to be involved in immune and inflammatory responses via multiple signaling pathways, leading to the production of proinflammatory cytokines. The purpose of this study was to investigate the role of GSK‐3β in the pathogenesis of lupus nephritis in 2 mouse models. Methods Thiadiazolidinone 8 (TDZD‐8), a selective inhibitor of GSK‐3β, was administered intraperitoneally to 12‐week‐old MRL/ lpr mice for 8 weeks or to 22‐week‐old (NZB × NZW)F1 mice for 12 weeks. The expression of GSK‐3β and NLRP3 inflammasome components was analyzed. Proteinuria, biochemical parameters, proinflammatory cytokines, anti–double‐stranded DNA (anti‐dsDNA) antibody levels, and renal pathology were examined. In vitro, the effect of GSK‐3β–directed small interfering RNA (siRNA) on NLRP3 inflammasome activation was evaluated in bone marrow–derived macrophages (BMMs) from the mice and in the J774A.1 macrophage cell line. Results The incidence of severe proteinuria and renal inflammation was significantly attenuated in both models, with a significant reduction in anti‐dsDNA antibody production, immune complex deposition in the kidney, and circulating proinflammatory cytokine levels. TDZD‐8 inhibited the activation of GSK‐3β and caspase 1, with a concomitant decrease in interleukin‐1β (IL‐1β) synthesis. In vitro, GSK‐3β siRNA transfection of mouse BMMs and the J774A.1 cell line with GSK‐3β siRNA inhibited the expression of GSK‐3β, the activation of caspase 1, and the production of IL‐1β. Conclusion These results show that GSK‐3β promotes lupus nephritis at least partly by activating the NLRP3/IL‐1β pathway. The linking of GSK‐3β to the NLRP3/IL‐1β pathway is a novel observation in our study. Our results suggest that the GSK‐3β/NLRP3/IL‐1β pathway may be a potential therapeutic target for lupus in humans.
Abstract 15535: Particulate Matter Exposure Worsens Atherogenic Profile in “Ground Zero” Workers
Authors: Venkatesh Mani, Simonette T Sawit, Cynara Maceda, Claudia Calcagno, Stephanie Wong, Zahi A Fayad, Jacqueline Moline, Mary Ann McLaughlin
Journal: Circulation (2011)

Background: Exposure to particulate matter (PM) is associated with adverse health effects leading to increased morbidity. Law enforcement workers were exposed to high levels of particulate pollutio...
Participants should be given feedback about the trial
Authors: S. Marshall
Journal: BMJ (1996)

EDITOR,—Elizabeth Wager and colleagues have set out extremely useful guidelines for gaining patients' consent to enter clinical trials.1 I have undertaken an anonymous, retrospective postal survey of 90 patients who participated in five trials of treatment for rheumatoid arthritis and one for ankylosing spondylitis. Seventy patients returned questionnaires (78% response rate). Most (69) thought that they had received a full explanation of the study and (67) that they had not been put under any pressure to take part, and all …
Development of an orthotopic bladder tumor model in mice and demonstration of antitumor efficacy with an oncolytic adenovirus CG8840 for the treatment of bladder cancer
Authors: Nagarajan Ramesh, Ying Ge, Jun Liu, Deborah Farson, Melinda Van Roey, Virginia Rojas, Dechao Yu
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

5134 

Replication-restricted oncolytic adenoviruses (OAV) have been developed for a number of tumor indications and many of them are under active investigation in clinical trials. We had earlier developed an OAV CG8840 for the treatment of uroplakin II-positive bladder tumor. In vitro studies demonstrated the preferential cytolytic activity of the virus and its efficacy in subcutaneous bladder tumor models in nude mice. Orthotopic animal models of bladder cancer more closely model the location and behavior of bladder tumors in human than non-orthotopic models. An orthotopic tumor model using the human bladder transitional cell carcinoma cell line SW780 was established on the luminal surface of the nude mice bladder. Initial seeding of the tumor cells involved the instillation of 1 x 106 tumor cells in a volume of 100 μl into the bladder lumen with a 25G catheter. The mouth of the urethra was closed with a purse string for 1 hr to allow time for attachment of the tumor cells to the bladder wall. Employing the Xenogen imaging system, in vivo imaging of the orthotopic tumor growth in mice was made possible through the use of a luciferase-expressing subclone SW780-Luc. The growth of the orthotopic tumors was assessed through the changes in the measured photon counts of the tumors. Growth in tumors sufficient for efficacy studies was observed within two weeks. The human origin of the tumors in the bladder was confirmed by immuno-histochemical staining with human anti-cytokeratin staining. Orthotopic tumors of SW780-Luc cells in bladder closely resembled superficial tumors in humans histologically. We had earlier demonstrated the enhancement in the infectivity of bladder epithelium with adenovirus following pretreatment with dodecyl-β-D-Maltoside (Ramesh et al., 2003). Similar pretreatment with 0.1% dodecyl-β-D-Maltoside was required for the efficient infection of the orthotopic tumors with adenovirus. Studies were undertaken to test the efficacy of the uroplakin II-positive bladder tumor-specific OAV CG8840 in reducing the tumor burden following intravesical instillation of the virus. Treatment of orthotopic SW780 bladder tumors with three doses of CG8840 (1x 1010 vp/treatment for 3 consecutive weeks) was efficacious in reducing tumor burden. A non-bladder specific OAV exhibited no antitumor activity. Immuno-histochemical examination of the bladder after 6 weeks showed complete absence of tumor cell in CG8840 treated mice. This simplified technique consistently produced a high incidence of superficial human tumor in mice. This will also be a useful model to conduct intravesical anti-tumor efficacy studies of OAV in combination with other therapeutic agents.
Mortality in anorexia nervosa
Authors: P F Sullivan
Journal: American Journal of Psychiatry (1995)

The author's goal was to shed light on the debate regarding the mortality rate over time associated with anorexia nervosa.He conducted a meta-analytic study using weighted linear regression to combine crude mortality proportions from 42 published studies to estimate the mortality associated with anorexia nervosa over time.The crude rate of mortality due to all causes of death for subjects with anorexia nervosa in these studies was 5.9% (178 deaths in 3,006 subjects). The aggregate mortality rate was estimated to be 0.56% per year, or approximately 5.6% per decade.The aggregate estimated mortality rate for subjects with anorexia nervosa is substantially greater than that reported for female psychiatric inpatients and for the general population.
Intersalt revisited: further analyses of 24 hour sodium excretion and blood pressure within and across populations
Authors: P. Elliott, J. Stamler, R. Nichols, A. R Dyer, R. Stamler, H. Kesteloot, M. Marmot
Journal: BMJ (1996)

<h3>Abstract</h3> <b>Objectives</b>: To assess further the relation in Intersalt of 24 hour urinary sodium to blood pressure of individuals and populations, and the difference in blood pressure from young adulthood into middle age. <b>Design</b>: Standardised cross sectional study within and across populations. <b>Setting</b>: 52 population samples in 32 countries. <b>Subjects</b>: 10 074 men and women aged 20-59. <b>Main outcome measures</b>: Association of sodium and blood pressure from within population and cross population multiple linear regression analyses with multivariate correction for regression dilution bias. Relation of sample median daily urinary sodium excretion to difference in blood pressure with age. <b>Results</b>: In within population analyses (n=10 074), individual 24 hour urinary sodium excretion higher by 100 mmol (for example, 170 v 70 mmol) was associated with systolic/diastolic blood pressure higher on average by 3/0 to 6/3 mm Hg (with and without body mass in analyses). Associations were larger at ages 40-59. In cross population analyses (n=52), sample median 24 hour sodium excretion higher by 100 mmol was associated with median systolic/diastolic pressure higher on average by 5-7/2-4 mm Hg, and estimated mean difference in systolic/diastolic pressure at age 55 compared with age 25 greater by 10-11/6 mm Hg. <b>Conclusions</b>: The strong, positive association of urinary sodium with systolic pressure of individuals concurs with Intersalt cross population findings and results of other studies. Higher urinary sodium is also associated with substantially greater differences in blood pressure in middle age compared with young adulthood. These results support recommendations for reduction of high salt intake in populations for prevention and control of adverse blood pressure levels. <h3>Key messages</h3> The within population findings were previously underestimated because of incomplete correction for the regression dilution problem Revised estimates of the within population association of sodium to blood pressure in Intersalt are concordant with the cross population findings for 52 samples Estimates of the effect of median sodium excretion higher by 100 mmol/day over a 30 year period (age 55 minus age 25) were a greater difference of 10-11 mm Hg in systolic blood pressure and 6 mm Hg in diastolic blood pressure These results lend further support to recommendations for mass reduction of high salt intake for the prevention and control of adverse blood pressure levels and high blood pressure in populations
Vaccination Compliance and the US Measles Epidemic—Reply
Authors: Maimuna S. Majumder, Jane E. Huston, John S. Brownstein
Journal: JAMA Pediatrics (2015)

In Reply We were interested to read the responses to our Research Letter regarding substandard vaccine compliance and the 2015 Disneyland measles outbreak. The authors raise several questions regarding our modeling method and resulting vaccination rate estimates.
Abstract 18498: Description of Aortic Root Growth and Outcomes in a Cohort of Pediatric Patients with Loeys-Dietz Syndrome
Authors: Nitya Viswanathan, Shaine A Morris
Journal: Circulation (2014)

Background: Loeys Dietz Syndrome (LDS) is associated with rapid aortic dilation and aortic dissection, but data on children with LDS are limited. The goal of this study is to describe aortic root growth and outcomes in children with LDS. Methods: Patients with LDS were identified from an institutional database. Data regarding genetic mutation, medications, aortic root dimensions by transthoracic echocardiography (TTE), aortic dissection and surgical intervention were collected. For those with &gt;2 TTEs 1 year apart, rate of change in z-score was calculated using linear regression. TTEs performed after aortic surgery were excluded. We examined if variables were associated with rate of aortic root growth. Results: Of 16 patients, 8 were female. Five had a TGFBR1 and 9 had a TGFBR2 mutation; 2 patients did not have genetic data available. Median aortic root Z-score at diagnosis was 3.5 (range 0.5-25.4). Fifteen patients were on medication (2 beta-blocker (BB), 5 angiotensin receptor blocker (ARB), 5 BB+ARB, and 3 with past use of both). Four patients underwent prophylactic root replacement at ages 3.3, 6.7, 8.7, and 9.4 years at root dimensions 3.2, 6.5, 4.0, and 4.1 cm respectively. One patient had a Type A dissection at age 15y after prior root replacement and underwent repeat surgery. Another underwent heart transplant at 6.9 years old after prior root replacement. Ten patients had serial TTE data. Median change in aortic root diameter and Z-score was 0.11cm/year and 0.1/year respectively. Mean change in z-score per year for those on on BB was -0.1± (range -1.2 to 0.7), ARB 0.5 (range 0.1 to 1.1) and both 0.0 (range -0.2 to 0.2, p=NS). No variables studied were associated with faster aortic growth. Conclusions: Degree of aortic root dilation and rate of aortic root growth is highly variable in children with LDS, although factors associated more aggressive disease are unclear. The high proportion of patients with adverse outcomes including aortic dissection and surgery is concerning.
Novel Findings from CNVs Implicate Inhibitory and Excitatory Signaling Complexes in Schizophrenia
Authors: Andrew J Pocklington, Elliott Rees, James T R Walters, Jun Han, David H Kavanagh, Kimberly D Chambert, Peter Holmans, Jennifer L Moran, Steven A McCarroll, George Kirov, Michael C O'Donovan, Michael J Owen
Journal: Neuron (2015)

We sought to obtain novel insights into schizophrenia pathogenesis by exploiting the association between the disorder and chromosomal copy number (CNV) burden. We combined data from 5,745 cases and 10,675 controls with other published datasets containing genome-wide CNV data. In this much-enlarged sample of 11,355 cases and 16,416 controls, we show for the first time that case CNVs are enriched for genes involved in GABAergic neurotransmission. Consistent with non-genetic reports of GABAergic deficits in schizophrenia, our findings now show disrupted GABAergic signaling is of direct causal relevance, rather than a secondary effect or due to confounding. Additionally, we independently replicate and greatly extend previous findings of CNV enrichment among genes involved in glutamatergic signaling. Given the strong functional links between the major inhibitory GABAergic and excitatory glutamatergic systems, our findings converge on a broad, coherent set of pathogenic processes, providing firm foundations for studies aimed at dissecting disease mechanisms.
Treatment of Pulmonary Embolism With Thrombolysis
Authors: Mark Metersky
Journal: Circulation (1998)

questions would be the performance of a randomized trial.We described such a trial in an editorial several years ago. 3 Currently, a pilot phase of a trial examining the influence of medical therapy versus revascularization in these patients is under way in the Veterans Affairs system.Although a similar trial has been proposed to the National Institutes of Health, this project has not received sufficient prioritization to be funded.Part of the funding concerns for this trial are due to the very large numbers and long-term follow-up that would be required to develop a satisfactory answer.Because the short-term risks of coronary revascularization for many patients can only be overcome by longterm benefit, any trial designed to study patients isolated to the perioperative period is not likely to show a benefit from revascularization.
Abstract 12760: Left Ventricular (LV) Remodeling in Aortic Regurgitation Differs From Athlete’s Heart With Similar LV Volumes and is Closely Related to Different Fiber Stress Distribution
Authors: Kaspar Broch, Stefano deMarchi, Richard Massey, Svend Aakhus, Lars Gullestad, Stig Urheim
Journal: Circulation (2014)

Introduction: Elite endurance athletes often develop left ventricular dilatation comparable to that observed in aortic regurgitation (AR). Hypothesis: We hypothesized that the LV remodeling observed in athlete’s heart differs from that seen in AR, and that the difference may be attributed to different fiber stress distribution. Methods: Thirty asymptomatic patients with moderate to severe AR, 15 age matched elite endurance athletes (Athl) and 17 age matched healthy controls (C) where analyzed with 3D speckle tracking echocardiography. We calculated the ratio between peak systolic circumferential (CS) - and peak systolic longitudinal strain (LS) and end-systolic (ES) circumferential (ESSc) and meridional (ESSm) fiber stress. Results: LV ejection fraction in C, Athl and AR patients was (61 ± 2, 61 ± 3 and 62 ± 3%, respectively, p=NS). LV end-diastolic volume was 78 ± 11, 112 ± 13 and 117 ± 20 ml/m 2 in C, Athl and AR, respectively, (C vs AR and Athl, p&lt;0.01, AR vs Athl, p=NS). A non-uniform contraction pattern with a rightward shift of the LS strain curve was observed in AR (Figure 1). The CS/LS ratio was 0.91 ± 0.11, 0.91 ± 0.16 and 1.12 ± 0.24 in C, Athl and AR, respectively, (AR vs C and Athl, p&lt;0.01, C vs Athl, p=NS). Consistently, the ESSc/ESSm ratio was similar in C and Athl (1.75 ± 0.08 and 1.74 ± 0.07, respectively, p=NS) and lower in AR patients (1.67 ± 0.07, AR vs C and Athl, p&lt;0.01), indicating a relative increase in meridional fiber stress in the AR group (Figure 2). Conclusions: We have demonstrated that LV remodeling in AR patients differs from athlete’s heart with similar LV volumes, and may be attributed to a shift in the circumferential-meridional fiber stress ratio in AR patients.
Recurrent Fusion of PCM1 to JAK2 in Atypical Chronic Myeloid Leukemia and Acute Leukemia Associated with the t(8;9)(p21-22;p23-24).
Authors: Andreas Reiter, Christoph Walz, Ann Watmore, Claudia Schoch, Ilona Blau, Nick Telford, Shilani Aruliah, John Yin, Danny Vanstraelen, Helen Barker, Peter Taylor, Aisling O’Driscoli, Brigitte Schlegelberger, Ute Berger, Andreas Hochhaus, Rüdiger Hehlmann, Andrew Chase, Nicholas C.P. Cross
Journal: Blood (2004)
Prevention of Left Ventricular Remodeling With Granulocyte Colony-Stimulating Factor After Acute Myocardial Infarction
Authors: Hüseyin Ince, Michael Petzsch, Hans Dieter Kleine, Heike Eckard, Tim Rehders, Detlev Burska, Stephan Kische, Mathias Freund, Christoph A. Nienaber
Journal: Circulation (2005)

Background— Experimental and clinical evidence has recently shown that pluripotent stem cells can be mobilized by granulocyte colony-stimulating factor (G-CSF) and may enhance myocardial regeneration early after primary percutaneous coronary intervention (PCI) management of acute myocardial infarction. Sustained or long-term effects of mobilized CD34-positive mononuclear stem cells, however, are unknown. Methods and Results— Thirty consecutive patients with ST-elevation myocardial infarction undergoing primary PCI with stenting and abciximab were selected for the study 85±30 minutes after PCI; 15 patients were randomly assigned to receive subcutaneous G-CSF at 10 μg/kg body weight for 6 days in addition to standard care including aspirin, clopidogrel, an angiotensin-converting enzyme inhibitor, β-blocking agents, and statins. In patients with comparable demographics and clinical and infarct-related characteristics, G-CSF stimulation led to sustained mobilization of CD34 positive mononuclear cells (MNC CD34+ ), with a 20-fold increase (from 3±2 at baseline to 66±54 MNC CD34+ /μL on day 6; P &lt;0.001); there was no evidence of leukocytoclastic effects, accelerated restenosis rate, or any late adverse events. Within 4 months, G-CSF–induced MNC CD34+ mobilization led to enhanced resting wall thickening in the infarct zone of 1.16±0.29 mm ( P &lt;0.05 versus control), which was sustained at 1.20±0.28 after 12 months ( P &lt;0.001 versus control). Similarly, left ventricular ejection fraction improved from 48±4% at baseline to 54±8% at 4 months ( P &lt;0.005 versus control) and 56±9% at 12 months ( P &lt;0.003 versus control and paralleled by sustained improvement of wall-motion score index from 1.70±0.22 to 1.42±0.26 and 1.33±0.21 at 4 and 12 months, respectively), after G-CSF ( P &lt;0.05 versus baseline and P &lt;0.03 versus controls). Accordingly, left ventricular end-diastolic diameter showed no remodeling and stable left ventricular dimensions after G-CSF stimulation, whereas left ventricular end-diastolic diameter in controls revealed enlargement from 55±4 mm at baseline to 58±4 mm ( P &lt;0.05 versus baseline) at 12 months after infarction and no improvement in diastolic function. Conclusion— Mobilization of MNC CD34+ by G-CSF after primary PCI may offer a pragmatic strategy for improvement in ventricular function and prevention of left ventricular remodeling 1 year after acute myocardial infarction.
HLA-DQA1*0103-DQB1*0601 Haplotype and –Positive Gastric Mucosa–Associated Lymphoid Tissue Lymphoma
Authors: Y KAWAHARA, M MIZUNO, T YOSHINO, K YOKOTA, K OGUMA, H OKADA, S FUJIKI, Y SHIRATORI
Journal: Clinical Gastroenterology and Hepatology (2005)
Inhibition of in vitro spontaneous apoptosis by IL-7 correlates with Bcl-2 up-regulation, cortical/mature immunophenotype, and better early cytoreduction of childhood T-cell acute lymphoblastic leukemia
Authors: Leonid Karawajew, Velia Ruppert, Christian Wuchter, Annett Kösser, Martin Schrappe, Bernd Dörken, Wolf-Dieter Ludwig
Journal: Blood (2000)
The relation between skin disorders and vitamin D
Authors: H.C. Wulf
Journal: British Journal of Dermatology (2012)

Vitamin D deficiency has been related to a high number of health disorders including skin cancer, autoimmune skin disorders, photodermatoses, atopic dermatitis and psoriasis. Special attention has been given to UVB phototherapy, as UVB is needed to convert 7‐dehydrocholesterol to previtamin D3 in the skin. When assessing vitamin D [measured as 25‐hydroxyvitamin D, 25(OH)D] in a given skin disease, attention is normally paid to the degree of insufficiency and the percentage of patients with serum 25(OH)D below 50 nmol L−1 (insufficiency). The following confounding factors should be kept in mind. (i) At what time of the year was sampling performed? In northern Europe serum 25(OH)D falls by about 1 nmol L−1 per week, corresponding to a total decrease of 25–35 nmol L−1 during winter.1, 2 (ii) Dietary supplementation habits.3 Most diets contain very little vitamin D. Oily fish contains high levels, and fish/seal liver contains very high levels. Certain food products are fortified with vitamin D, and supplementation is becoming increasingly frequent. (iii) 25(OH)D analysis method. The gold standard, high‐pressure liquid chromatography–mass spectrometry (HPLC‐MS), is expensive to perform, and other methods are most commonly used. The percentage of the study population that is 25(OH)D deficient/insufficient is very dependent on the analysis methodology.4, 5 Snellman et al.4 analysed serum 25(OH)D by three methods and found 8% insufficiency using HPLC‐MS, 22% insufficiency using a radioimmunoassay and 43% using a chemiluminescent immunoassay.
Pulmonary tuberculosis relapse or atypical mycobacterium infection
Authors: Abdelhamid Ben Amar, Nada Rahmouni, Nawel Chaouch, Mourad Zarrouk, Saoussan Bacha, Sana Cheikh Rouhou, Hajer Racil, Abdellatif Chabbou
Journal: European Respiratory Journal (2012)

In endemic countries, pulmonary tuberculosis (PTb) relapse is the first diagnosis evoked when patients with previous history of PTb develop respiratory symptoms. The diagnosis of atypical mycobacterial infection (AMI) complicating Tb sequelae is often accidentally discovered.  In order to precise predictors features of AMI, we analyzed all cases of AMI complicating PTb sequellae in immunocompetent patients diagnosed 2006 through 2011. AMI diagnosis was based on American Thoracic Society criteria.  Only 4 AMI cases were collected. All patients were male, smokers and aged 37, 40, 42 and 54 years respectively. Two patients were ethylic and 1 asthmatic. No patient had HIV infection. Clinical and radiological presentation simulates PTb in all cases. Chest radiography showed PTb sequellae, excavated opacities and apical nodules. All patients had positive smear bacilli and were then treated as a PTB relapse. But outcome was unfavorable in all cases. Sputum culture revealed in all cases AMI (1 M. avium, 1 M. Kansasii, 1 M. Abscessus, 1 M.). The average time to diagnosis was 3.3 months due to culture needs. Evolution under treatment adapted to the antibiogram was favorable in two cases.  Our results show, that diagnosis of AMI complicating PTb sequellae is difficult and diagnosis delay is relatively long due to culture necessity. Frequently positive Smear bacilli and no specific signs (clinical, biological, radiological) were associated to AMI leading to confusing diagnosis. Only sputum culture allows the distinction between typical and atypical mycobacterium infection. In PTb relpse, AMI should always be kept in mind.