tbuckley/cabot-search huggingface dataset:
Aryl hydrocarbon receptor mediates laminar fluid shear stress-induced CYP1A1 activation and cell cycle arrest in vascular endothelial cells
Authors: Z. Han, Y. Miwa, H. Obikane, M. Mitsumata, F. Takahashi-Yanaga, S. Morimoto, T. Sasaguri
Journal: Cardiovascular Research (2007)

We investigated the mechanisms of shear stress (SS)-induced activation of cytochrome P450 (CYP) 1A1 and cell cycle arrest with regard to the role of the aryl hydrocarbon receptor (AhR), since AhR mediates the expression of CYP1A1 induced by polycyclic aromatic hydrocarbons (PAHs) and is thought to be involved in the regulation of cell growth and differentiation. Human umbilical vein endothelial cells (ECs) were exposed to laminar SS and thereafter collected to evaluate the expression, activity, and transcription of CYP1A1 and the expression of AhR and cell cycle-related proteins. A physiological level of laminar SS (15 dynes/cm2) markedly increased the expression level and enzymatic activity of CYP1A1. SS stimulated CYP1A1 promoter activity without influencing mRNA stability. Loss of two functional xenobiotic response elements (XREs) in the 5′-flanking region of the CYP1A1 gene suppressed the SS-induced transcription of CYP1A1. Laminar SS stimulated the expression and nuclear translocation of AhR. α-Naphthoflavone, an AhR antagonist, and a small interfering RNA (siRNA) for AhR significantly suppressed SS-induced CYP1A1 expression. The siRNA also abolished SS-induced cell cycle arrest, the expression of the cyclin-dependent kinase inhibitor p21Cip1, and dephosphorylation of retinoblastoma protein. Laminar SS stimulated the transcription of CYP1A1 through the activation of AhR in a way that is similar to the effects of PAHs. AhR was also involved in cell cycle arrest induced by SS. Our results suggest that sustained activation of AhR exposed to blood flow plays an important role in the regulation of EC functions.
Spatiotemporal Regulation of Small GTPases as Revealed by Probes Based on the Principle of Förster Resonance Energy Transfer (FRET): Implications for Signaling and Pharmacology
Authors: Etsuko Kiyokawa, Kazuhiro Aoki, Takeshi Nakamura, Michiyuki Matsuda
Journal: The Annual Review of Pharmacology and Toxicology (2011)

Low molecular weight (“small”) GTPases are key regulators of a number of signaling cascades. Each GTPase is regulated by numerous guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), and each GTPase binds to numerous effector proteins in a GTP-dependent manner. In many instances, individual regulators activate more than one GTPase, and each effector binds to one or more GTPases belonging to the same family. To untangle these complex networks, probes based on the principle of Förster resonance energy transfer (FRET) are widely used. Here, we provide an overview of the probes based on FRET and examples of discoveries achieved with them. In the process, we attempt to delineate the merits, current limitations, and future applications of this technique to pharmacological studies.
Effect of uric acid on plasma levels of 1,25(OH)2D in renal failure.
Authors: R Vanholder, S Patel, C H Hsu
Journal: Journal of the American Society of Nephrology (1993)

Previous studies from these laboratories have demonstrated that uremic biologic fluids contain substances that suppress 1,25(OH)2D metabolism. Among these substances, it was found that uric acid suppresses 1 alpha-hydroxylase activity and synthesis of 1,25(OH)2D in rats. In this study, the effect of uric acid on plasma concentrations of 1,25(OH)2D in patients with renal failure was examined. Nine patients with stable chronic renal failure (serum creatinine, 1.9 to 6.4 mg/dL) were studied. None of the patients received vitamin D supplementation. Plasma concentrations of Ca, P, parathyroid hormone, creatinine, uric acid, 1,25(OH)2D, and 25(OH)D were measured before and 1 wk after the patients received allopurinol, 300 mg daily. Plasma creatinine, Ca, P, parathyroid hormone, and 25(OH)D did not change before or after allopurinol treatment. However, plasma uric acid decreased significantly from 7.3 +/- 0.4 to 4.0 +/- 0.4 mg/dL (P < 0.01) and plasma concentration of 1,25(OH)2D rose from 30.8 +/- 2.7 to 38.2 +/- 4.8 pg/mL (P < 0.01) after the ingestion of allopurinol. Allopurinol itself did not appear to directly enhance 1 alpha-hydroxylase activity in rats. It was concluded that a short-term administration of allopurinol suppresses plasmic uric acid and increases plasma 1,25(OH)2D in patients with chronic mild to moderate renal failure.
Testing the Circadian Gene Hypothesis in Prostate Cancer: A Population-Based Case-Control Study
Authors: Yong Zhu, Richard G. Stevens, Aaron E. Hoffman, Liesel M. FitzGerald, Erika M. Kwon, Elaine A. Ostrander, Scott Davis, Tongzhang Zheng, Janet L. Stanford
Journal: Cancer Research (2009)

Circadian genes are responsible for maintaining the ancient adaptation of a 24-hour circadian rhythm and influence a variety of cancer-related biological pathways, including the regulation of sex hormone levels. However, few studies have been undertaken to investigate the role of circadian genes in the development of prostate cancer, the most common cancer type among men (excluding nonmelanoma skin cancer). The current genetic association study tested the circadian gene hypothesis in relation to prostate cancer by genotyping a total of 41 tagging and amino acid-altering single nucleotide polymorphisms (SNP) in 10 circadian-related genes in a population-based case-control study of Caucasian men (n = 1,308 cases and 1,266 controls). Our results showed that at least one SNP in nine core circadian genes (rs885747 and rs2289591 in PER1; rs7602358 in PER2; rs1012477 in PER3; rs1534891 in CSNK1E; rs12315175 in CRY1; rs2292912 in CRY2; rs7950226 in ARNTL; rs11133373 in CLOCK; and rs1369481, rs895521, and rs17024926 in NPAS2) was significantly associated with susceptibility to prostate cancer (either overall risk or risk of aggressive disease), and the risk estimate for four SNPs in three genes (rs885747 and rs2289591 in PER1, rs1012477 in PER3, and rs11133373 in CLOCK) varied by disease aggressiveness. Further analyses of haplotypes were consistent with these genotyping results. Findings from this candidate gene association study support the hypothesis of a link between genetic variants in circadian genes and prostate cancer risk, warranting further confirmation and mechanistic investigation of circadian biomarkers in prostate tumorigenesis.
Polymorphisms in<i>XRCC1</i>,<i>XRCC3</i>, and<i>CCND1</i>and Survival After Treatment for Metastatic Breast Cancer
Authors: Mary A. Bewick, Michael S.C. Conlon, Robert M. Lafrenie
Journal: Journal of Clinical Oncology (2006)

Single nucleotide polymorphisms (SNPs) in DNA repair and cell cycle control genes may alter protein function and therefore the efficacy of DNA damaging chemotherapy. We retrospectively evaluated the association of SNPs in DNA repair genes, XRCC1-01 (Arg399Gln) and XRCC3-01 (Thr241Met), and a cell cycle control gene, CCND1-02 (A870G), with progression-free survival (PFS) and breast cancer specific survival (BCSS) in patients with metastatic breast cancer (MBC).SNPs in 95 patients with MBC enrolled onto one of five prospective clinical trials of high-dose chemotherapy and autologous stem-cell transplantation were evaluated using genotyping assays.For XRCC1-01, the hazard ratio (HR) for BCSS was 2.8 (95% CI, 1.60 to 5.00) and the HR for PFS was 2.0 (95%CI, 1.12 to 3.43). For XRCC3-01, the HR for BCSS was 2.0 (95%CI, 1.12 to 3.70) and the HR for PFS was 2.0 (95%CI, 1.09 to 3.59). For CCND1-02, the HR for BCSS was 1.8 (95%CI, 1.12 to 2.78) and the HR for PFS was 1.8 (95%CI, 1.15 to 2.85). Patients carrying one variant genotype (HR, 1.7; 95%CI, 1.07 to 2.82) or combinations of any two variant genotypes (HR, 4.7; 95% CI, 2.41 to 8.94) had significantly poorer BCSS compared with patients carrying zero variants. In multivariable analysis, XRCC1-01, presence of liver metastases, and bone metastases independently predicted BCSS. Combinations of any two variant genotypes were stronger independent predictors of BCSS and PFS than the presence of liver or bone metastases.XRCC1-01, XRCC3-01, and CCND1-01 may be predictive of survival outcome in patients with MBC treated with DNA damaging chemotherapy.
Phase II Trial of Murine 131I-Labeled Antitenascin Monoclonal Antibody 81C6 Administered Into Surgically Created Resection Cavities of Patients With Newly Diagnosed Malignant Gliomas
Authors: D. A. Reardon
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To assess the efficacy and toxicity of intraresection cavity 131I-labeled murine antitenascin monoclonal antibody 81C6 and determine its true response rate among patients with newly diagnosed malignant glioma. PATIENTS AND METHODS: In this phase II trial, 120 mCi of 131I-labeled murine 81C6 was injected directly into the surgically created resection cavity of 33 patients with previously untreated malignant glioma (glioblastoma multiforme [GBM], n = 27; anaplastic astrocytoma, n = 4; anaplastic oligodendroglioma, n = 2). Patients then received conventional external-beam radiotherapy followed by a year of alkylator-based chemotherapy. RESULTS: Median survival for all patients and those with GBM was 86.7 and 79.4 weeks, respectively. Eleven patients remain alive at a median follow-up of 93 weeks (range, 49 to 220 weeks). Nine patients (27%) developed reversible hematologic toxicity, and histologically confirmed, treatment-related neurologic toxicity occurred in five patients (15%). One patient (3%) required reoperation for radionecrosis. CONCLUSION: Median survival achieved with 131I-labeled 81C6 exceeds that of historical controls treated with conventional radiotherapy and chemotherapy, even after accounting for established prognostic factors including age and Karnofsky performance status. The median survival achieved with 131I-labeled 81C6 compares favorably with either 125I interstitial brachy-therapy or stereotactic radiosurgery and is associated with a significantly lower rate of reoperation for radionecrosis. Our results confirm the efficacy of 131I-labeled 81C6 for patients with newly diagnosed malignant glioma and suggest that a randomized phase III study is indicated.
Mechanical and Electrophysiological Substrate for Recurrent Atrial Flutter Detected by Right Atrial Speckle Tracking Echocardiography and Electroanatomic Mapping in Myotonic Dystrophy Type 1
Authors: Piercarlo Ballo, Marzia Giaccardi, Andrea Colella, Fabrizio Cellerini, Fabrizio Bandini, Leandro Chiodi, Alfredo Zuppiroli
Journal: Circulation (2013)
Metastatic Pheochromocytoma/Paraganglioma Related to Primary Tumor Development in Childhood or Adolescence: Significant Link to <i>SDHB</i> Mutations
Authors: Kathryn S. King, Tamara Prodanov, Vitaly Kantorovich, Tito Fojo, Jacqueline K. Hewitt, Margaret Zacharin, Robert Wesley, Maya Lodish, Margarita Raygada, Anne-Paule Gimenez-Roqueplo, Shana McCormack, Graeme Eisenhofer, Dragana Milosevic, Electron Kebebew, Constantine A. Stratakis, Karel Pacak
Journal: Journal of Clinical Oncology (2011)

Purpose To present data on the high rate of SDHB mutations in patients with metastatic pheochromocytoma/paraganglioma whose initial tumor presentation began in childhood or adolescence. Patients and Methods From 2000 to 2010, 263 patients with pheochromocytoma/paraganglioma were evaluated through the National Institutes of Health (NIH), Bethesda, MD. Of the 263 patients, 125 patients were found to have metastatic disease; of these 125 patients, 32 patients presented with a tumor before 20 years of age. An additional 17 patients presented with a tumor before 20 years of age but demonstrated no development of metastatic disease. Genetic testing for mutations in the VHL, MEN, and SDHB/C/D genes was performed on patients without previously identified genetic mutations. Results Of the 32 patients who presented with metastatic disease and had their primary tumor in childhood or adolescence, sequence analysis of germline DNA showed SDHB mutations in 23 patients (71.9%), SDHD mutations in three patients (9.4%), VHL mutations in two patients (6.3%), and an absence of a known mutation in four patients (12.5%). The majority of these 32 patients (78.1%) presented with primary tumors in an extra-adrenal location. Conclusion The majority of patients with metastatic pheochromocytoma/paraganglioma who presented with a primary tumor in childhood/adolescence had primary extra-adrenal tumors and harbored SDHB mutations. Except for primary tumors located in the head and neck where SDHD genetic testing is advised, we recommend that patients who present with metastatic pheochromocytoma/paraganglioma with primary tumor development in childhood or adolescence undergo SDHB genetic testing before they undergo testing for other gene mutations, unless clinical presentation or family history suggests a different mutation.
THE BACTERIOLOGY OF TRICHOMYCOSIS AXILLARIS
Authors: M. E. McBRIDE, R. G. FREEMAN, J. M. KNOX
Journal: British Journal of Dermatology (1968)

SUMMARY. A method is described for the isolation and culture of the causative organisms of trichomycosis axillaris. Hairs from 7 cases, 6 of the yellow variety and one of the red, have been examined. Three species of Corvnebacteria were isolated from each of the 6 cases and 2 were isolated from the seventh. The species from the cases with the red granules were similar to those isolated from those with the yellow granules. It was concluded from these results that it was unjustifiable to refer to the causative agent of this disease as a single agent such as C. tenuis.
INDUCTION OF A HEMOLYSIN RESPONSE IN VITRO
Authors: Klaus-Ulrich Hartmann
Journal: The Journal of Experimental Medicine (1971)

Spleen cells of bone marrow chimeras (B cells) and of irradiated mice injected with thymus cells and heterologous erythrocytes (educated T cells) were mixed and cultured together (17). The number of PFC developing in these cultures was dependent both on the concentration of the B cells and of the educated T cells. In excess of T cells the number of developing PFC is linearly dependent on the number of B cells. At high concentrations of T cells more PFC developed; the increase in the number of PFC was greatest between the 3rd and 4th day of culture. Increased numbers of educated T cells also assisted the development of PFC directed against the erythrocytes. It is concluded that the T cells not only play a role during the triggering of the precursor cells but also during the time of proliferation of the B cells; close contact between B and T cells seems to be needed to allow the positive activity of the T cells.
Atypical Cross Talk Between Mentalizing and Mirror Neuron Networks in Autism Spectrum Disorder
Authors: Inna Fishman, Christopher L. Keown, Alan J. Lincoln, Jaime A. Pineda, Ralph-Axel Müller
Journal: JAMA Psychiatry (2014)

Converging evidence indicates that brain abnormalities in autism spectrum disorder (ASD) involve atypical network connectivity, but it is unclear whether altered connectivity is especially prominent in brain networks that participate in social cognition.To investigate whether adolescents with ASD show altered functional connectivity in 2 brain networks putatively impaired in ASD and involved in social processing, theory of mind (ToM) and mirror neuron system (MNS).Cross-sectional study using resting-state functional magnetic resonance imaging involving 25 adolescents with ASD between the ages of 11 and 18 years and 25 typically developing adolescents matched for age, handedness, and nonverbal IQ.Statistical parametric maps testing the degree of whole-brain functional connectivity and social functioning measures.Relative to typically developing controls, participants with ASD showed a mixed pattern of both over- and underconnectivity in the ToM network, which was associated with greater social impairment. Increased connectivity in the ASD group was detected primarily between the regions of the MNS and ToM, and was correlated with sociocommunicative measures, suggesting that excessive ToM-MNS cross talk might be associated with social impairment. In a secondary analysis comparing a subset of the 15 participants with ASD with the most severe symptomology and a tightly matched subset of 15 typically developing controls, participants with ASD showed exclusive overconnectivity effects in both ToM and MNS networks, which were also associated with greater social dysfunction.Adolescents with ASD showed atypically increased functional connectivity involving the mentalizing and mirror neuron systems, largely reflecting greater cross talk between the 2. This finding is consistent with emerging evidence of reduced network segregation in ASD and challenges the prevailing theory of general long-distance underconnectivity in ASD. This excess ToM-MNS connectivity may reflect immature or aberrant developmental processes in 2 brain networks involved in understanding of others, a domain of impairment in ASD. Further, robust links with sociocommunicative symptoms of ASD implicate atypically increased ToM-MNS connectivity in social deficits observed in ASD.
Precursors of colony-forming cells in humans can be distinguished from colony-forming cells by expression of the CD33 and CD34 antigens and light scatter properties.
Authors: R G Andrews, J W Singer, I D Bernstein
Journal: The Journal of Experimental Medicine (1989)

We determined whether human marrow cells that directly form colonies in vitro could be distinguished from cells that generate or become CFC only after LTMC in the presence of irradiated marrow stromal cells. In previous studies, an anti-CD33 antibody, L4F3, and complement (C') were used to lyse nearly all CFC in marrow, and the remaining cells generated CFC in LTMC. In the present studies, marrow cells were treated with L4F3 + C' and the remaining CD33- cells were separated into CD34+ and CD34- populations and placed in LTMC. Only the CD34+ cells were found to generate significant numbers of CFC. To compare the CD33-CD34+ and CD33+CD34+ cells, we isolated each cell population using two-color FACS. Only LTMCs of the CD33-CD34+ cells generated CFC for greater than 5 wk. In contrast, cells that expressed both the CD33 and CD34 antigens, which contained most of the CFC, generated few CFC in LTMC. Fractionation of marrow cells based on right angle and forward light scattering suggested that precursors for CFC have low right angle and low forward light scattering properties. The CD33-CD34+ marrow cells were therefore further fractionated based on light scatter characteristics. Cells with low right angle and low forward light scatter formed few or no colonies on direct culture, yet generated greater numbers of CFC after 4 wk of LTMC than did cells with low right angle and high forward light scatter. Most (87-98%) CFC generated in the LTMCs that were initiated with CD33-CD34+ cells were found to express the CD33 antigen. Thus, hematopoietic progenitors with differing proliferative and differentiative potentials can be directly separated on the basis of their expression of CD33 and CD34 cell surface antigens and their light scatter properties.
Patterns of Recurrence After Surgery Alone Versus Preoperative Chemoradiotherapy and Surgery in the CROSS Trials
Authors: Vera Oppedijk, Ate van der Gaast, Jan J.B. van Lanschot, Pieter van Hagen, Rob van Os, Caroline M. van Rij, Maurice J. van der Sangen, Jannet C. Beukema, Heidi Rütten, Patty H. Spruit, Janny G. Reinders, Dick J. Richel, Mark I. van Berge Henegouwen, Maarten C.C.M. Hulshof
Journal: Journal of Clinical Oncology (2014)

To analyze recurrence patterns in patients with cancer of the esophagus or gastroesophageal junction treated with either preoperative chemoradiotherapy (CRT) plus surgery or surgery alone.Recurrence pattern was analyzed in patients from the previously published CROSS I and II trials in relation to radiation target volumes. CRT consisted of five weekly courses of paclitaxel and carboplatin combined with a concurrent radiation dose of 41.4 Gy in 1.8-Gy fractions to the tumor and pathologic lymph nodes with margin.Of the 422 patients included from 2001 to 2008, 418 were available for analysis. Histology was mostly adenocarcinoma (75%). Of the 374 patients who underwent resection, 86% were allocated to surgery and 92% to CRT plus surgery. On January 1, 2011, after a minimum follow-up of 24 months (median, 45 months), the overall recurrence rate in the surgery arm was 58% versus 35% in the CRT plus surgery arm. Preoperative CRT reduced locoregional recurrence (LRR) from 34% to 14% (P < .001) and peritoneal carcinomatosis from 14% to 4% (P < .001). There was a small but significant effect on hematogenous dissemination in favor of the CRT group (35% v 29%; P = .025). LRR occurred in 5% within the target volume, in 2% in the margins, and in 6% outside the radiation target volume. In 1%, the exact site in relation to the target volume was unclear. Only 1% had an isolated infield recurrence after CRT plus surgery.Preoperative CRT in patients with esophageal cancer reduced LRR and peritoneal carcinomatosis. Recurrence within the radiation target volume occurred in only 5%, mostly combined with outfield failures.
Interventions to promote walking: systematic review
Authors: David Ogilvie, Charles E Foster, Helen Rothnie, Nick Cavill, Val Hamilton, Claire F Fitzsimons, Nanette Mutrie
Journal: BMJ (2007)

<b>Objective</b> To assess the effects of interventions to promote walking in individuals and populations. <b>Design</b> Systematic review. <b>Data sources</b> Published and unpublished reports in any language identified by searching 25 electronic databases, by searching websites, reference lists, and existing systematic reviews, and by contacting experts. <b>Review methods</b> Systematic search for and appraisal of controlled before and after studies of the effects of any type of intervention on how much people walk, the distribution of effects on walking between social groups, and any associated effects on overall physical activity, fitness, risk factors for disease, health, and wellbeing. <b>Results</b> We included 19 randomised controlled trials and 29 non-randomised controlled studies. Interventions tailored to people9s needs, targeted at the most sedentary or at those most motivated to change, and delivered either at the level of the individual (brief advice, supported use of pedometers, telecommunications) or household (individualised marketing) or through groups, can encourage people to walk more, although the sustainability, generalisability, and clinical benefits of many of these approaches are uncertain. Evidence for the effectiveness of interventions applied to workplaces, schools, communities, or areas typically depends on isolated studies or subgroup analysis. <b>Conclusions</b> The most successful interventions could increase walking among targeted participants by up to 30-60 minutes a week on average, at least in the short term. From a perspective of improving population health, much of the research currently provides evidence of efficacy rather than effectiveness. Nevertheless, interventions to promote walking could contribute substantially towards increasing the activity levels of the most sedentary.
Multicenter phase II–III study of oxaliplatin plus cyclophosphamide vs. cisplatin plus cyclophosphamide in chemonaive advanced ovarian cancer patients
Authors: J.-L. Misset, Ph. Vennin, Ph. Chollet, P. Pouillart, Ph. Laplaige, J.L. Frobert, D. Castera, M. Fabro, D. Langlois, E. Cortesi, V. Lucas, E. Gamelin, A. Laadem, J. Otero
Journal: Annals of Oncology (2001)