tbuckley/cabot-search huggingface dataset:
Intensified fractional CO<sub>2</sub>laser-assisted photodynamic therapy vs. laser alone for organ transplant recipients with multiple actinic keratoses and wart-like lesions: a randomized half-side comparative trial on dorsal hands
Authors: P. Helsing, K. Togsverd-Bo, M.B. Veierød, G. Mørk, M. Haedersdal
Journal: British Journal of Dermatology (2013)

Journal Article Intensified fractional CO2 laser‐assisted photodynamic therapy vs. laser alone for organ transplant recipients with multiple actinic keratoses and wart‐like lesions: a randomized half‐side comparative trial on dorsal hands Get access P. Helsing, P. Helsing Department of Dermatology Oslo University Hospital‐Rikshospitalet N‐0027 Oslo Norway Correspondence Per Helsing. E‐mail: phelsing@ous-hf.no Search for other works by this author on: Oxford Academic Google Scholar K. Togsverd‐Bo, K. Togsverd‐Bo Department of Dermatology Bispebjerg Hospital University of Copenhagen Copenhagen 2400 Denmark Search for other works by this author on: Oxford Academic Google Scholar M.B. Veierød, M.B. Veierød Department of Biostatistics Institute of Basic Medical Sciences University of Oslo N‐0317 Oslo Norway Search for other works by this author on: Oxford Academic Google Scholar G. Mørk, G. Mørk Department of Dermatology Oslo University Hospital‐Rikshospitalet N‐0027 Oslo Norway Search for other works by this author on: Oxford Academic Google Scholar M. Hædersdal M. Hædersdal Department of Dermatology Bispebjerg Hospital University of Copenhagen Copenhagen 2400 Denmark Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 169, Issue 5, 1 November 2013, Pages 1087–1092, https://doi.org/10.1111/bjd.12507 Published: 01 November 2013
Successful treatment of meningeal involvement in Wegener's granulomatosis with infliximab
Authors: J Hermann
Journal: Annals of the Rheumatic Diseases (2006)

Meningeal involvement in Wegener’s granulomatosis (WG) is rare and only 32 cases have been reported by Reinhold-Keller and coworkers.1,2 The outcome of the disease has improved with the institution of cytotoxic agents.3 We report on a patient with WG and progressive pachymeningeosis despite treatment with cyclophosphamide (CyC) and glucocorticoids who responded well to infliximab treatment.

In December 2003 a 34 year old male chemist was diagnosed with localised WG, according to the American College of Rheumatology criteria and the Capel Hill Conference criteria, on the basis of granulomatous nasal inflammation, left-sided otitis media, and the detection of proteinase-3-antineutrophilic cytoplasmic antibodies (PR3-ANCA) >100 U/ml (normal <5 U/ml).4,5 Because …
Lymphedema and Quality of Life in Breast Cancer Survivors: The Iowa Women's Health Study
Authors: Rehana L. Ahmed, Anna Prizment, DeAnn Lazovich, Kathryn H. Schmitz, Aaron R. Folsom
Journal: Journal of Clinical Oncology (2008)

Purpose The impact of lymphedema or related arm symptoms on health-related quality of life (HRQOL) in breast cancer (BrCa) survivors has not been examined using a large population-based cohort. Patients and Methods The Iowa Women's Health Study (IWHS) collected self-report data for lymphedema, arm symptoms, and HRQOL (Medical Outcomes Study Short Form-36) in 2004 and data for cancer diagnosis, treatment, and behavioral and health characteristics between 1986 and 2003. We studied 1,287 women, age 55 to 69 years at baseline, who developed unilateral BrCa. We used cross-sectional analyses to describe the prevalence of lymphedema and arm symptoms and multivariate-adjusted generalized linear models to compare HRQOL (physical functioning, bodily pain, general health, physical and emotional role limitations, vitality, social functioning, and mental health) between the following three survivor groups: women with lymphedema (n = 104), women with arm symptoms without diagnosed lymphedema (n = 475), and women without lymphedema or arm symptoms (n = 708). Results The mean (± SE) time between BrCa diagnosis and lymphedema survey was 8.1 ± 0.2 years. Of BrCa survivors, 8.1% self-reported diagnosed lymphedema, and 37.2% self-reported arm symptoms. Knowledge of lymphedema was low among survivors without diagnosed lymphedema (n = 1,183). After multivariate adjustment, women with diagnosed lymphedema or arm symptoms without diagnosed lymphedema had lower physical and mental HRQOL compared with women without lymphedema or arm symptoms. Effect sizes were mild to moderate. There was a dose-response relation between number of arm symptoms and lower HRQOL. Conclusion In the IWHS, HRQOL was lower for BrCa survivors with diagnosed lymphedema and for those with arm symptoms without diagnosed lymphedema. Clinical trials are needed to determine what interventions can improve lymphedema and impact HRQOL for BrCa survivors.
Inflammatory Stress and Idiosyncratic Hepatotoxicity: Hints from Animal Models
Authors: Xiaomin Deng, James P. Luyendyk, Patricia E. Ganey, Robert A. Roth
Journal: Pharmacological Reviews (2009)

Adverse drug reactions (ADRs) present a serious human health problem. They are major contributors to hospitalization and mortality throughout the world (Lazarou et al., 1998; Pirmohamed et al., 2004). A small fraction (less than 5%) of ADRs can be classified as "idiosyncratic." Idiosyncratic ADRs (IADRs) are caused by drugs with diverse pharmacological effects and occur at various times during drug therapy. Although IADRs affect a number of organs, liver toxicity occurs frequently and is the primary focus of this review. Because of the inconsistency of clinical data and the lack of experimental animal models, how IADRs arise is largely undefined. Generation of toxic drug metabolites and induction of specific immunity are frequently cited as causes of IADRs, but definitive evidence supporting either mechanism is lacking for most drugs. Among the more recent hypotheses for causation of IADRs is that inflammatory stress induced by exogenous or endogenous inflammagens is a susceptibility factor. In this review, we give a brief overview of idiosyncratic hepatotoxicity and the inflammatory response induced by bacterial lipopolysaccharide. We discuss the inflammatory stress hypothesis and use as examples two drugs that have caused IADRs in human patients: ranitidine and diclofenac. The review focuses on experimental animal models that support the inflammatory stress hypothesis and on the mechanisms of hepatotoxic response in these models. The need for design of epidemiological studies and the potential for implementation of inflammation interaction studies in preclinical toxicity screening are also discussed briefly.
Predicting Change in Academic Abilities After Conformal Radiation Therapy for Localized Ependymoma
Authors: Heather M. Conklin, Chenghong Li, Xiaoping Xiong, Robert J. Ogg, Thomas E. Merchant
Journal: Journal of Clinical Oncology (2008)

Conformal radiation therapy (CRT) aims to limit the highest radiation dose to the tissue volume at risk while sparing surrounding normal tissues. This study investigated whether treatment of childhood ependymoma with CRT would preserve cognitive function. Academic competence was chosen as the primary outcome measure given it is a measure of applied cognitive abilities in a child's natural setting.Eighty-seven pediatric patients diagnosed with ependymoma received CRT in which doses ranging from 54.0 to 59.4 Gy were prescribed to the postoperative tumor bed with a 10-mm clinical target volume margin. Cognitive testing was conducted at the start of CRT, 6 months, and annually after the start of CRT. The median length of follow-up was 59.6 months. Academic testing included subtests from the Wechsler Individual Achievement Test (WIAT) and the Achenbach Child Behavior Checklist.Linear mixed models with random coefficients revealed a modest but significant decline in reading scores during follow-up (WIAT slope estimate -0.064 +/- 0.028 points/month; P = .026). Math and spelling performance remained stable. Supratentorial tumor location and multiple surgeries were predictive of worse reading performance at CRT baseline. Male sex, longer symptomatic interval, pre-CRT chemotherapy, pre-existing endocrine deficiencies, hydrocephalus, and younger age at CRT (< 5 years) were predictive of a significant decline in reading scores over time.CRT may result in better long-term cognitive outcomes when compared to conventional radiation therapy approaches. Reading appears more vulnerable than other academic skills and may decline over time despite stable intellectual functioning.
Sodium-sensitive calcium binding to sarcolemma-enriched preparations from canine ventricle.
Authors: M B Frankis, G E Lindenmayer
Journal: Circulation Research (1984)

Calcium binding to sarcolemma-enriched preparations from canine ventricle was evaluated. The preparation was exposed to calcium and 45Ca at physiological ionic strength, pH 7.4, for 15-18 hours at 5 degrees C. Bound calcium was separated from free by filtration and washing of the filter with solutions containing calcium and LaCl3. After equilibration at 5 degrees C, exposure to 37 degrees C caused an irreversible loss of binding. Monovalent cations (157 mM) reduced calcium binding: Na+ much greater than Li+ greater than Cs+ greater than K+ greater than Rb+ approximately equal to choline. In 1 microM calcium, divalent cations (3 mM) reduced binding: Sr++ greater than Ba++ greater than Mg++ approximately equal to Mn++. At 1-300 microM calcium, inhibition of the sodium-sensitive component of binding was characterized by I50's of 3.2-9.5 mM sodium. Comparison of binding by centrifugation versus filtration suggested that the sodium-sensitive component resided on constituents within the membrane vesicles. Calcium binding in 1 mM ethyleneglycol-bis-(beta-aminoethylether)N,N'-tetraacetic acid at pH 7.1 and 5 degrees C, revealed a single species of sodium-sensitive calcium-binding sites: Kd = 0.052 microM and Bmax = 6.73 nmol/mg. In 3 mM magnesium, the Kd was 0.205 microM and the Bmax was 9.03 nmol/mg. Nearly complete inhibition of binding was observed as sodium was raised from 1 to 10 mM. Thus, a substantial number of calcium-binding sites were detected at 5 degrees C in 3 mM magnesium at physiological ionic strength and pH 7.1. The affinity of these sites was in the range necessary to modulate intracellular free calcium. The sensitivity to sodium was at the lower end of the range estimated for intracellular sodium.
Integrin and Growth Factor Receptor Crosstalk
Authors: Brian P. Eliceiri
Journal: Circulation Research (2001)

Crosstalk between integrins and growth factor receptors are an important signaling mechanism to provide specificity during normal development and pathological processes in vascular biology. Evidence from several model systems demonstrates the physiological importance of the coordination of signals from growth factors and the extracellular matrix to support cell proliferation, migration, and invasion in vivo. Several examples of crosstalk between these two important classes of receptors indicate that integrin ligation is required for growth factor-induced biological processes. Furthermore, integrins can directly associate with growth factor receptors, thereby regulating the capacity of integrin/growth factor receptor complexes to propagate downstream signaling. Recent data suggest that antagonists of alpha(v) integrins can provide a therapeutic benefit in human cancer patients, whereas knockout mice lacking specific integrins can provide an interesting insight into the role of integrins during development. This review will focus on the biological importance of integrin and growth factor receptor crosstalk that occurs during cell growth, migration, and invasion as well as in endothelial cells during angiogenesis.
IL23R Arg381Gln is associated with childhood onset inflammatory bowel disease in Scotland
Authors: J Van Limbergen, %R K Russell, E R Nimmo, H E Drummond, L Smith, G Davies, N H Anderson, P M Gillett, P McGrogan, K Hassan, L Weaver, W M Bisset, G Mahdi, D C Wilson, J Satsangi
Journal: Gut (2007)

The discovery of NOD2/CARD15 as the first susceptibility gene in Crohn’s disease has contributed significantly to a fundamental change in the direction of basic research in inflammatory bowel disease (IBD), triggering renewed interest in the integrity of the innate immune response in IBD and appropriate orchestration of a subsequent adaptive immune response.1,2 More widely, in all complex diseases this finding in 2001 provided a much welcomed and needed proof of principle for non-parametric linkage analysis.

Another study with major implications for the pathogenesis of Crohn’s disease as well as for investigation of all complex disorders has recently been published.3 The North American consortium performed an association study testing 308 332 markers spanning the entire genome in 567 patients with ileal Crohn’s disease and 571 controls of non-Jewish European ancestry. Of the three markers reported to retain significance after stringent Bonferroni correction, two were located in the NOD2/CARD15 gene. The third marker (rs11209026) was a non-synonymous variant in the interleukin-23 receptor (IL23R) gene on chromosome 1p31. Replication was obtained in the index paper in a Jewish ancestry case-control analysis of patients with Crohn’s disease by transmission disequilibrium testing in 883 families with offspring affected by IBD and in a combined case-control analysis …
Prognostic markers in patients with antineutrophil cytoplasmic autoantibody-associated microscopic polyangiitis and glomerulonephritis.
Authors: S L Hogan, P H Nachman, A S Wilkman, J C Jennette, R J Falk
Journal: Journal of the American Society of Nephrology (1996)

The purpose of this study was to determine the prognostic value of clinical, laboratory, and pathologic features at the time of presentation on patient and renal survival in patients with antineutrophil cytoplasmic autoantibody (ANCA)-associated microscopic polyangiitis and glomerulonephritis (excluding Wegener's granulomatosis). One hundred seven ANCA-positive patients with necrotizing and crescentic glomerulonephritis, including 69 with evidence for microscopic polyangiitis, were evaluated for this study. The relative risk of death was calculated for the following potential prognostic indicators: (1) ANCA pattern; (2) pulmonary hemorrhage at onset; (3) presence of extrarenal manifestations versus renal limited disease; and (4) treatment with corticosteroids and cyclophosphamide (intravenous or oral), compared with corticosteroids alone. Cox's proportional hazard model was used to assess the predictive value of the following variables on renal survival: (1) age; (2) race; (3) pulmonary symptoms at onset of disease; (4) renal pathology; (5) ANCA pattern; and (6) peak serum creatinine values obtained near the time of renal biopsy. Patients were followed prospectively for 2.5 yr (range, 5 days to 12 yr 2 months). There were 12 disease-related deaths and 46 patients who reached ESRD. The relative risk (and 95% confidence interval) of patient death was 8.65 (3.36, 22.2) times greater in patients who presented with pulmonary hemorrhage, and 3.78 (1.22, 11.70) times greater in patients with cytoplasmic ANCA compared to those with perinuclear ANCA. The relative risk of pulmonary hemorrhage was no different by ANCA pattern. The risk of death was 5.56 times lower in the cyclophosphamide-treated patients versus those treated with corticosteroids alone. The predictors of renal survival were entry serum creatinine value (P = 0.0002), race (African Americans having a worse outcome compared with Caucasians, P = 0.0008), and the presence of arterial sclerosis on kidney biopsy (P = 0.0076) when controlling for age, ANCA pattern, microscopic polyangiitis versus glomerulonephritis alone, and pulmonary involvement. Pathology indices such as glomerular necrosis, glomerular crescents, glomerular sclerosis, and interstitial sclerosis were not predictive of renal survival when controlling for entry serum creatinine value, race, and arterial sclerosis. However, in the subgroup of patients with a peak creatinine value of < or = 3.0 mg/dL (N = 29), increased interstitial sclerosis was a predictor of a poor renal outcome (P = 0.04).
Pentraxin 3 Induces Vascular Endothelial Dysfunction Through a P-selectin/Matrix Metalloproteinase-1 Pathway
Authors: Albino Carrizzo, Paola Lenzi, Claudio Procaccini, Antonio Damato, Francesca Biagioni, Mariateresa Ambrosio, Giuseppina Amodio, Paolo Remondelli, Carmine Del Giudice, Raffaele Izzo, Alberto Malovini, Luigi Formisano, Vincenzo Gigantino, Michele Madonna, Annibale A. Puca, Bruno Trimarco, Giuseppe Matarese, Francesco Fornai, Carmine Vecchione
Journal: Circulation (2015)

Pentraxin 3 (PTX3), the prototype of long pentraxins, has been described to be associated with endothelial dysfunction in different cardiovascular disorders. No study has yet evaluated the possible direct effect of PTX3 on vascular function.Through in vitro experiments of vascular reactivity and ultrastructural analyses, we demonstrate that PTX3 induces dysfunction and morphological changes in the endothelial layer through a P-selectin/matrix metalloproteinase-1 pathway. The latter hampered the detachment of endothelial nitric oxide synthase from caveolin-1, leading to an impairment of nitric oxide signaling. In vivo studies showed that administering PTX3 to wild-type mice induced endothelial dysfunction and increased blood pressure, an effect absent in P-selectin-deficient mice. In isolated human umbilical vein endothelial cells, PTX3 significantly blunted nitric oxide production through the matrix metalloproteinase-1 pathway. Finally, using ELISA, we found that hypertensive patients (n=31) have higher plasma levels of PTX3 and its mediators P-selectin and matrix metalloproteinase-1 than normotensive subjects (n=21).Our data show for the first time a direct role of PTX3 on vascular function and blood pressure homeostasis, identifying the molecular mechanisms involved. The findings in humans suggest that PTX3, P-selectin, and matrix metalloproteinase-1 may be novel biomarkers that predict the onset of vascular dysfunction in hypertensive patients.
Sequence specificity incompletely defines the genome-wide occupancy of Myc
Authors: Jiannan Guo, Tiandao Li, Joshua Schipper, Kyle A Nilson, Francis K Fordjour, Jeffrey J Cooper, Raluca Gordân, David H Price
Journal: Genome biology (2014)

The Myc-Max heterodimer is a transcription factor that regulates expression of a large number of genes. Genome occupancy of Myc-Max is thought to be driven by Enhancer box (E-box) DNA elements, CACGTG or variants, to which the heterodimer binds in vitro.
Inference of Positive and Negative Selection on the 5′ Regulatory Regions of Drosophila Genes
Authors: Michael H. Kohn, Shu Fang, Chung-I Wu
Journal: Molecular Biology and Evolution (2004)

Both positive selection and negative selection have been shown to drive the evolution of coding regions. It is of interest to know if the corresponding 5′ regions of genes may be subjected to selection of comparable intensities. For such a comparison, we chose the \(\underline{Ac}\) cessory gland \(\underline{p}\) rotein (Acp) genes as our test case. About 700 bp and 600 bp for the 5′ and coding regions, respectively, of eight previously unstudied genes were sequenced from 21 isogenic lines of D. melanogaster and one line from D. simulans. The ratio of divergence at the amino-acid replacement sites (A) over that at the synonymous sites (S) was twice the ratio for common polymorphism. Interestingly, the 5′ region shows the same trend, with the 5′/S divergence ratio being 1.8 times higher than the 5′/S ratio for common polymorphism. There are several possible explanations for the 5′/S ratios, including demography, negative selection, and positive selection. Under normal conditions, positive selection is the most likely explanation. If that is true, about 45 to 50 percent of all fixed differences at both the replacement and 5′ sites were adaptive, even though the substitution rate in the former is only half that of the latter (KA/KS ∼ 0.3 vs. K5′/KS ∼ 0.6). As previous analyses have indicated, the inclusion of slightly deleterious polymorphism confounds the inference of positive selection. The analysis of published polymorphism data covering 97 verified 5′ regions of Drosophila suggests more pronounced selective constraint on the 5′ untranslated region and the core promoter (together corresponding to ∼200 bp in this data set) when compared to the more distal portion of the 5′ region of genes.
Marijuana Use and Risk of Oral Squamous Cell Carcinoma
Authors: Karin A. Rosenblatt, Janet R. Daling, Chu Chen, Karen J. Sherman, Stephen M. Schwartz
Journal: Cancer Research (2004)

Previous laboratory investigations, case reports, and a hospital-based case-control study have suggested that marijuana use may be a risk factor for squamous cell head and neck cancer. We conducted a population-based case-control study to determine whether marijuana use is associated with the development of oral squamous cell carcinoma (OSCC). Case subjects (n = 407) were 18-65-year-old residents of three counties in western Washington State who were newly diagnosed with OSCC from 1985 through 1995. Control subjects (n = 615), who were similar to the cases with respect to age and sex, were selected from the general population using random-digit telephone dialing. Lifetime histories of marijuana use and exposure to known OSCC risk factors were ascertained using a structured questionnaire. Information on genetic polymorphisms in glutathione S-transferase enzymes was obtained from assays on participant DNA. Odds ratios for associations with features of marijuana use were adjusted for sex, education, birth year, alcohol consumption, and cigarette smoking. A similar proportion of case subjects (25.6%) and control subjects (24.4%) reported ever use of marijuana (adjusted odds ratio, 0.9; 95% confidence interval, 0.6-1.3). There were no trends in risk observed with increasing duration or average frequency of use or time since first or last use. No subgroup defined by known or suspected OSCC risk factors (age, cigarette smoking, alcohol consumption, and genetic polymorphisms) showed an increased risk. Marijuana use was not associated with OSCC risk in this large, population-based study.
Protective Immunity to Nematode Infection Is Induced by CTLA-4 Blockade
Authors: Kathy McCoy, Mali Camberis, Graham Le Gros
Journal: The Journal of Experimental Medicine (1997)

The recent observation that neutralization or genetic deletion of the T lymphocyte receptor CTLA-4 allows enhanced T cell reactivity offers new opportunities for immunotherapy against infectious agents. We used a neutralizing antibody to block CTLA-4 interaction with its ligands CD80 and CD86 during infection of mice with the nematode, Nippostrongylus brasiliensis. CTLA-4 blockade greatly enhanced and accelerated the T cell immune response to N. brasiliensis, resulting in a profound reduction in adult worm numbers and early termination of parasite egg production. The ability of CTLA-4 blockade to accelerate primary immune responses to a protective level during an acute infection indicates its potential as an immunotherapeutic tool for dealing with infectious agents.