tbuckley/cabot-search huggingface dataset:
Atopic and nonatopic eczema in adolescence: is there a difference?
Authors: E.K. Johansson, N. Ballardini, A. Bergström, I. Kull, C.-F. Wahlgren
Journal: British Journal of Dermatology (2015)

Journal Article Atopic and nonatopic eczema in adolescence: is there a difference? Get access E.K. Johansson, E.K. Johansson Dermatology and Venereology Unit Department of Medicine Solna Karolinska Institutet Stockholm SwedenDermatological and Venereal Clinic Södersjukhuset Stockholm Sweden Correspondence Emma K. Johansson. E‐mail: emma.johansson@sodersjukhuset.se Search for other works by this author on: Oxford Academic Google Scholar N. Ballardini, N. Ballardini Sachs' Children and Youth Hospital Södersjukhuset Stockholm SwedenInstitute of Environmental Medicine Karolinska Institutet Stockholm Sweden Search for other works by this author on: Oxford Academic Google Scholar A. Bergström, A. Bergström Institute of Environmental Medicine Karolinska Institutet Stockholm Sweden Search for other works by this author on: Oxford Academic Google Scholar I. Kull, I. Kull Institute of Environmental Medicine Karolinska Institutet Stockholm SwedenDepartment of Clinical Science and Education Södersjukhuset Karolinska Institutet Stockholm Sweden Search for other works by this author on: Oxford Academic Google Scholar C.‐F. Wahlgren C.‐F. Wahlgren Dermatology and Venereology Unit Department of Medicine Solna Karolinska Institutet Stockholm SwedenDepartment of Dermatology Karolinska University Hospital Solna Stockholm Sweden Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 173, Issue 4, 1 October 2015, Pages 962–968, https://doi.org/10.1111/bjd.13901 Published: 01 October 2015
Efficacy of initial methotrexate monotherapy versus combination therapy with a biological agent in early rheumatoid arthritis: a meta-analysis of clinical and radiographic remission
Authors: B. Kuriya, E. V. Arkema, V. P. Bykerk, E. C. Keystone
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Objective</h3> The target outcome in early rheumatoid arthritis (ERA) is now remission. This meta-analysis compared the efficacy of initial methotrexate monotherapy versus combination therapy (methotrexate plus biological agent) for clinical remission and radiographic non-progression among ERA patients with minimal or no previous methotrexate exposure. <h3>Methods</h3> A systematic search was performed for randomised controlled trials of ERA using predefined criteria. A random effects model was used to pool the risk ratio (RR) for clinical and radiographic remission at 52–56 weeks of follow-up. <h3>Results</h3> Seven trials of combination therapy with infliximab, adalimumab, etanercept or abatacept were included. The majority of studies defined clinical remission as a 28-joint disease activity score (DAS28) of 2.6 or less. Radiographic non-progression was primarily defined as a modified total Sharp score change of less than 0.5 units. All trials demonstrated risk estimates in favour of combination therapy: the pooled RR for achieving clinical remission was 1.74 (95% CI 1.54 to 1.98) and for radiographic non-progression was 1.30 (95% CI 1.01 to 1.68). Significant heterogeneity among studies for the latter outcome was detected (p&lt;0.001). <h3>Conclusions</h3> The efficacy of combination therapy with a biological agent is superior to methotrexate monotherapy for remission. Combination therapy has a greater initial effect on clinical remission than radiographic non-progression. Uniform definitions of remission are needed and the proportion of subjects who achieve the combined endpoint of clinical and radiographic remission should be considered as a meaningful outcome in future studies of ERA.
Targeting Pioneering Factor and Hormone Receptor Cooperative Pathways to Suppress Tumor Progression
Authors: Supriya Shah, Shikha Prasad, Karen E. Knudsen
Journal: Cancer Research (2012)

Abstract Nuclear receptors and pioneer factors drive the development and progression of prostate cancer. In this disease, aggressive disease phenotypes and hormone therapy failures result from resurgent activity of androgen receptor (AR) and the upregulation of coactivator protein p300 and pioneer factors (e.g., GATA2 and FOXA1). Thus, a major emphasis in the field is to identify mechanisms by which castrate-resistant AR activity and pioneer factor function can be combinatorially suppressed. Here we show that the turmeric spice isoflavone curcumin suppresses p300 and CBP occupancy at sites of AR function. Curcumin reduced the association of histone acetylation and pioneer factors, thereby suppressing AR residence and downstream target gene expression. Histone deacetylase inhibitors reversed the effects of curcumin on AR activity, further underscoring the impact of curcumin on altering the chromatin landscape. These functions precluded pioneer factor occupancy, leading ultimately to a suppression of ligand-dependent and ligand-independent AR residence on chromatin. Moreover, these functions were conserved even in cells with heightened pioneer factor activity, thus identifying a potential strategy to manage this subclass of tumors. Biological relevance was further identified using in vivo xenograft models mimicking disease progression. Curcumin cooperated in vivo with androgen deprivation as indicated by a reduction in tumor growth and delay to the onset of castrate-resistant disease. Together, our results show the combinatorial impact of targeting AR and histone modification in prostate cancer, thus setting the stage for further development of curcumin as a novel agent to target AR signaling. Cancer Res; 72(5); 1248–59. ©2012 AACR.
Importance of CXC Chemokine Receptor 2 in the Homing of Human Peripheral Blood Endothelial Progenitor Cells to Sites of Arterial Injury
Authors: Mihail Hristov, Alma Zernecke, Kiril Bidzhekov, Elisa A. Liehn, Erdenechimeg Shagdarsuren, Andreas Ludwig, Christian Weber
Journal: Circulation Research (2007)

Circulating endothelial progenitor cells (EPCs) may contribute to endothelial regeneration; however, the exact mechanisms of their arterial homing remain elusive. We examined the role of the angiogenic chemokine receptor CXCR2 in the homing of human EPCs. Isolated EPCs expressed CXCR2 together with kinase insert domain-containing receptor, CD31, vascular endothelial cadherin, and CXCR4. Adhesion assays under flow conditions showed that EPCs preferentially adhered to beta(2)-integrin ligands, that firm arrest on fibronectin or fibrinogen was enhanced by the CXCR2 ligands CXCL1 or CXCL7, and that blockade of CXCR2 significantly reduced EPC adhesion on platelet-coated endothelial matrix. This was corroborated by the involvement of CXCR2 in EPC recruitment to denuded areas of murine carotid arteries ex vivo and in vivo. Notably, blocking CXCR2 inhibited the incorporation of human EPCs expressing CXCR2 at sites of arterial injury in athymic nude mice. Immunoreactivity for the beta-thromboglobulin isoform CXCL7 was observed in murine platelets and denuded smooth muscle cells (SMCs) early after wire injury, and transcripts for CXCL7 and CXCL1 were detected in isolated human arterial SMCs. Human KDR(+)CXCR2(+) cells showed better in situ adhesion to injured murine carotid arteries than KDR(+)CXCR2(-) cells, were predominantly CD14(+), and improved CXCR2-dependent endothelial recovery after injury in nude mice. In conclusion, our data clearly demonstrate the importance of CXCR2 for the homing of circulating EPCs to sites of arterial injury and for endothelial recovery in vivo.
Role of shear stress and endothelial prostaglandins in flow- and viscosity-induced dilation of arterioles in vitro.
Authors: A Koller, D Sun, G Kaley
Journal: Circulation Research (1993)

We have studied the effect of changes in shear stress on diameter of isolated arterioles of rat cremaster muscle. The steady-state active diameter of arterioles at a constant perfusion pressure (60 mm Hg) was 80 +/- 1.2 microns. The vessels' passive diameter (Ca(2+)-free solution) was 156 +/- 1.8 microns. Changes in shear stress were induced either by an increase in flow (velocity) or by an increase in viscosity of the perfusion solution. At a constant perfusion pressure, the stepwise increase in perfusion flow (0-80 microliters/min in 10-microliters/min steps) elicited, with a delay of approximately 20 seconds, a gradual increase in diameter up to 46%. At a constant 20-microliters/min flow rate, increases in viscosity of the perfusate (2%, 4%, and 6% dextran [molecular weight, 77,800]) caused a gradual vasodilation up to 22%. Varying flow and viscosity of the perfusate simultaneously resulted in an upward shift of the flow-diameter curve. Both flow- and viscosity-induced dilations were eliminated by the removal of the endothelium of arterioles (by air) or were inhibited by indomethacin (10(-5) M). The efficacy and specificity of these inhibitory treatments were assessed with vasoactive agents whose action, with regard to endothelial mediation, has been determined previously. The arteriolar dilation maintained calculated wall shear stress close to control values during increases in flow and/or viscosity of the perfusate, but when the dilation was inhibited by removal of the endothelium or by indomethacin, wall shear stress increased significantly in a cumulative manner.(ABSTRACT TRUNCATED AT 250 WORDS)
Arsenic-Related Chromosomal Alterations in Bladder Cancer
Authors: L. E. Moore
Journal: JNCI Journal of the National Cancer Institute (2002)

Background: Previous studies have demonstrated that ingestion of arsenic in drinking water is a strong risk factor for several forms of cancer, including bladder cancer. It is not known whether arsenic-related cancers are genetically similar to cancers in unexposed individuals or what mechanisms of carcinogenesis may underlie their formation. This study was designed to compare chromosomal alterations in bladder cancers of arsenic-exposed individuals to provide insight into the mechanism of how arsenic may induce or promote cancer. Methods: A case–case study was conducted in Argentina and Chile examining chromosomal alterations in bladder tumor DNA in 123 patients who had been exposed to arsenic in their drinking water. Patients were placed into one of four arsenic exposure categories according to their average 5-year peak arsenic exposure. Patients were also classified as ever smokers or never smokers. Comparative genomic hybridization was used to identify chromosomal alterations throughout the genome. All statistical tests were two-sided. Results: The total number of chromosomal alterations was higher in individuals exposed to higher arsenic levels (5.7 ± 5.1, 5.6 ± 5.1, 7.3 ± 7.4, and 9.1 ± 6.5 [mean ± standard deviation] chromosomal alterations per tumor with increasing arsenic exposure; Ptrend = .02, adjusted for stage and grade). The trend was stronger in high-grade (G2–G3) tumors (6.3 ± 5.5, 8.3 ± 4.7, 10.3 ± 7.8, and 10.5 ± 6.4 alterations per tumor; Ptrend = .01) than it was in low-grade (G1) tumors (3.5 ± 3.1, 1.1 ± 1.1, 2.5 ± 2.5, and 3.6 ± 3.2 alterations per tumor; Ptrend = .79). The mean number of chromosomal alterations also increased with tumor stage and grade (Ptrend<.001) independently of arsenic exposure but was not associated with smoking history. Deletion of part or all of chromosome 17p (Ptrend<.001) showed the strongest association with arsenic exposure. Conclusions: Bladder tumors in patients with higher levels of arsenic exposure showed higher levels of chromosomal instability. Most of the chromosomal alterations associated with arsenic exposure were also associated with tumor stage and grade, raising the possibility that bladder tumors from arsenic-exposed patients may behave more aggressively than tumors from unexposed patients.
Breathing pattern and chest wall volumes during exercise in patients with cystic fibrosis, pulmonary fibrosis and COPD before and after lung transplantation
Authors: H. Wilkens, B. Weingard, A. Lo Mauro, E. Schena, A. Pedotti, G. W. Sybrecht, A. Aliverti
Journal: Thorax (2010)

Pulmonary fibrosis (PF), cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) often cause chronic respiratory failure (CRF).In order to investigate if there are different patterns of adaptation of the ventilatory pump in CRF, in three groups of lung transplant candidates with PF (n=9, forced expiratory volume in 1 s (FEV(1))=37+/-3% predicted, forced vital capacity (FVC)=32+/-2% predicted), CF (n=9, FEV(1)=22+/-3% predicted, FVC=30+/-3% predicted) and COPD (n=21, FEV(1)=21+/-1% predicted, FVC=46+/-2% predicted), 10 healthy controls and 16 transplanted patients, total and compartmental chest wall volumes were measured by opto-electronic plethysmography during rest and exercise.Three different breathing patterns were found during CRF in PF, CF and COPD. Patients with COPD were characterised by a reduced duty cycle at rest and maximal exercise (34+/-1%, p<0.001), while patients with PF and CF showed an increased breathing frequency (49+/-6 and 34+/-2/min, respectively) and decreased tidal volume (0.75+/-0.10 and 0.79+/-0.07 litres) (p<0.05). During exercise, end-expiratory chest wall and rib cage volumes increased significantly in patients with COPD and CF but not in those with PF. End-inspiratory volumes did not increase in CF and PF. The breathing pattern of transplanted patients was similar to that of healthy controls.There are three distinct patterns of CRF in patients with PF, CF and COPD adopted by the ventilatory pump to cope with the underlying lung disease that may explain why patients with PF and CF are prone to respiratory failure earlier than patients with COPD. After lung transplantation the chronic adaptations of the ventilatory pattern to advanced lung diseases are reversible and indicate that the main contributing factor is the lung itself rather than systemic effects of the disease.
The human adult cardiomyocyte phenotype
Authors: S Bird
Journal: Cardiovascular Research (2003)

Aim: Determination of the phenotype of adult human atrial and ventricular myocytes based on gene expression and morphology. Methods: Atrial and ventricular cardiomyocytes were obtained from patients undergoing cardiac surgery using a modified isolation procedure. Myocytes were isolated and cultured with or without serum. The relative cell attachment promoting efficiency of several reagents was evaluated and compared. Morphological changes during long-term culture were assessed with phase contrast microscopy, morphometric analysis and immunocytochemistry or RT-PCR of sarcomeric markers including α-actinin, myosin light chain-2 (MLC-2) and the adhesion molecule, cadherin. Results: The isolation method produced viable rod-shaped atrial (16.6±6.0%, mean±S.E.; n = 5) and ventricular cells (22.4±8.0%, mean±S.E.; n = 5) in addition to significant numbers of apoptotic and necrotic cells. Cell dedifferentiation was characterized by the loss of sarcomeric structure, condensation and extrusion of sarcomeric proteins. Cells cultured with low serum recovered and assumed a flattened, spread form with two distinct morphologies apparent. Type I cells were large, had extensive sarcolemmal spreading, with stress fibers and nascent myofibrils, whilst type II cells appeared smaller, with more mature myofibril organisation and focal adhesions. Conclusion: Characterization of the redifferentiation capabilities of cultured adult cardiac myocytes in culture, provides an important system for comparing cardiomyocytes differentiating from human stem cells and provides the basis for an in vitro transplantation model to study interaction and communication between primary adult and stem cell-derived cardiomyocytes.
Bilateral Panocular Involvement With Mantle-Cell Lymphoma
Authors: Aimee V. Chappelow, Arun D. Singh, Victor L. Perez, Alan Lichtin, Brad Pohlman, Roger Macklis
Journal: Journal of Clinical Oncology (2008)

A 51-year-old white woman presented with complaints of bilateral red eye of 2 weeks duration associated with photophobia and blurred vision. Seventeen months prior, she had begun a series of chemotherapy regimens for mantle-cell lymphoma (MCL), confirmed by fluorescent in situ hybridization and flow cytometry, that culminated in autologous stem-cell transplantation. On presentation to our clinic, she was receiving rituximab in combination with intrathecal cytarabine for leptomeningeal involvement. Visual acuity was 20/40intherighteyeandcountfingersat1footinthelefteye.External examination revealed multiple cutaneous eyelid nodules bilaterally and a salmon patch of the bulbar conjunctiva of the right eye (Fig 1). Slit-lampexaminationwassignificantforpseudohypopyon(lymphocytesintheanteriorchamber),irregularstromalthickeningoftheiris, and infiltration of the vitreous with lymphocytes (left eye more than right) bilaterally (Figs 1 and 2), indicative of anterior and posterior chamberinvolvementofbotheyeswithlymphoma.Shewasplacedon hourly prednisone eye drops. In addition, external-beam radiation treatment (EBRT) at a dose of 14 Gy (2 Gy in seven fractions) was administered as a cone down to the area of gross ocular disease, with an additional dose of 16 Gy (2 Gy in eight fractions) to the brain. One week after initiation of EBRT, ocular signs had resolved dramatically andvisualacuitywas20/40intherighteyeand20/50inthelefteye.In
Prevention of High-Dose Chemotherapy–Induced Cardiotoxicity in High-Risk Patients by Angiotensin-Converting Enzyme Inhibition
Authors: Daniela Cardinale, Alessandro Colombo, Maria T. Sandri, Giuseppina Lamantia, Nicola Colombo, Maurizio Civelli, Giovanni Martinelli, Fabrizio Veglia, Cesare Fiorentini, Carlo M. Cipolla
Journal: Circulation (2006)

Background— An increase in troponin I soon after high-dose chemotherapy (HDC) is a strong predictor of poor cardiological outcome in cancer patients. This finding has important clinical implications and provides a rationale for the development of prophylactic strategies for preventing cardiotoxicity. Angiotensin-converting enzyme inhibitors slow the progression of left ventricular dysfunction in different clinical settings, but their role in the prevention of cardiotoxicity has never been investigated. Methods and Results— Of the 473 cancer patients evaluated, 114 (72 women; mean age, 45±12 years) who showed a troponin I increase soon after HDC were randomized to receive (angiotensin-converting enzyme inhibitor group; 20 mg/d; n=56) or not to receive (control subjects; n=58) enalapril. Treatment was started 1 month after HDC and continued for 1 year. Cardiological evaluation was performed at baseline and at 1, 3, 6, and 12 months after HDC. The primary end point was an absolute decrease &gt;10 percent units in left ventricular ejection fraction, with a decline below the normal limit value. A significant reduction in left ventricular ejection fraction and an increase in end-diastolic and end-systolic volumes were observed only in untreated patients. According to the Kaplan-Meier analysis, the incidence of the primary end point was significantly higher in control subjects than in the angiotensin-converting enzyme inhibitor group (43% versus 0%; P &lt;0.001). Conclusions— In high-risk, HDC-treated patients, defined by an increased troponin I value, early treatment with enalapril seems to prevent the development of late cardiotoxicity.
Development and Evaluation of a Novel Solution, Somah, for the Procurement and Preservation of Beating and Nonbeating Donor Hearts for Transplantation
Authors: Hemant S. Thatte, Laki Rousou, Bader E. Hussaini, Xiu-Gui Lu, Patrick R. Treanor, Shukri F. Khuri
Journal: Circulation (2009)

Injury to myocytes, endocardium, and the coronary endothelium during harvesting and storage can compromise outcomes after heart transplantation. Safeguarding of structure and function of cardiomyocytes and endothelium in donor hearts may lead to improved patient survival after transplantation. Information gained from porcine hearts stored in standard transplant solution was used to design a superior preservation solution that would optimally protect and maintain organs from beating heart and/or nonbeating heart donors during long-term storage.Multiphoton microscopy was used to image deep within cardiac biopsies and coronary artery tissue harvested from porcine hearts obtained from beating heart and nonbeating heart donors for analysis of myocyte and endothelial cell structure and function. Cell structural integrity and viability, calcium mobilization, and nitric oxide generation were determined with fluorescence viability markers, immunofluorescence, and Western blots. During hypothermic storage in standard preservation solution, Celsior, myocyte, and endothelial viability was markedly attenuated in hearts obtained from beating heart donors. In contrast, hearts from beating and nonbeating heart donors stored in the newly formulated Somah solution demonstrated an increase in high-energy phosphate levels, protection of cardiac myocyte viability, mitochondrial membrane polarization, and structural proteins. Similarly, coronary artery endothelial organization and function, calcium mobilization, and nitric oxide generation were well maintained during temporal storage in Somah.The Celsior preservation solution in clinical use today has led to a profound decline in cardiomyocyte and endothelial cell viability, whereas the newly designed Somah solution has safeguarded myocyte and endothelial integrity and function during organ storage. Use of Somah as a storage medium may lead to optimized graft function and long-term patient survival after transplantation.
GAD Antibody in Mitochondrial Diabetes Associated With tRNA(UUR) Mutation at Position 3271
Authors: Yoshihiko Suzuki, Matsuo Taniyama, Akira Shimada, Yoshihito Atumi, Kempei Matsuoka, Yoshitomo Oka
Journal: Diabetes Care (2002)

A possible association of pancreatic autoimmunity with mitochondrial diabetes, which is associated with pathogenetic mitochondrial DNA (mtDNA) abnormalities (1), has been controversial. The study by Kobayashi et al. (2) and our study (3) previously reported that islet cell antibody (ICA) was detected in, respectively, 42% (13 of 31) and 18% (2 of 11) of patients with mitochondrial diabetes associated with tRNA(UUR) mutation at position 3243 (MD3243). These results support an mtDNA abnormality associated with ICA-related pancreatic autoimmune abnormality. Kobayashi et al. (2) and we (4) also reported that 6.5% (2 of 31) and 0% (0 of 11), respectively, of MD3243 patients had …