tbuckley/cabot-search huggingface dataset:
Axon-Glial Signaling and the Glial Support of Axon Function
Authors: Klaus-Armin Nave, Bruce D. Trapp
Journal: Annual Review of Neuroscience (2008)

Oligodendrocytes and Schwann cells are highly specialized glial cells that wrap axons with a multilayered myelin membrane for rapid impulse conduction. Investigators have recently identified axonal signals that recruit myelin-forming Schwann cells from an alternate fate of simple axonal engulfment. This is the evolutionary oldest form of axon-glia interaction, and its function is unknown. Recent observations suggest that oligodendrocytes and Schwann cells not only myelinate axons but also maintain their long-term functional integrity. Mutations in the mouse reveal that axonal support by oligodendrocytes is independent of myelin assembly. The underlying mechanisms are still poorly understood; we do know that to maintain axonal integrity, mammalian myelin-forming cells require the expression of some glia-specific proteins, including CNP, PLP, and MAG, as well as intact peroxisomes, none of which is necessary for myelin assembly. Loss of glial support causes progressive axon degeneration and possibly local inflammation, both of which are likely to contribute to a variety of neuronal diseases in the central and peripheral nervous systems.
Treatment allocation by minimisation
Authors: Douglas G Altman, J Martin Bland
Journal: BMJ (2005)

<h3>Abstract</h3> CS teargas is one of the most used tools for crowd-control worldwide. Exposure to CS teargas is known to have consequences on protesters’ health (i.e. eye, skin irritation, respiratory problems), but recent concerns have been raised over its potential gender-specific effects. Indeed, field and clinical observations report cases of menstrual cycle issues among female protesters following high exposure to teargas. The hypothesis of a link between teargas exposure and menstrual cycle issues is plausible from a physiological standpoint, but has not yet been empirically investigated. Using data from a cross-sectional study on Yellow Vests protesters’ health in France, we examined the relationship between exposure to teargas and menstrual cycle issues among female protesters (<i>n</i> = 145). Analyses suggested a positive link between exposure and menstrual cycle perturbations. These results constitute first and preliminary evidence that CS teargas may be linked with menstrual cycle among women, which need corroboration given the importance of this issue. We call for further research on the potential effects of CS teargas on women’s reproductive system.
Variants in Complement Factor H and Complement Factor H-Related Protein Genes, CFHR3 and CFHR1, Affect Complement Activation in IgA Nephropathy
Authors: Li Zhu, Ya-Ling Zhai, Feng-Mei Wang, Ping Hou, Ji-Cheng Lv, Da-Min Xu, Su-Fang Shi, Li-Jun Liu, Feng Yu, Ming-Hui Zhao, Jan Novak, Ali G. Gharavi, Hong Zhang
Journal: Journal of the American Society of Nephrology (2014)

Complement activation is common in patients with IgA nephropathy (IgAN) and associated with disease severity. Our recent genome-wide association study of IgAN identified susceptibility loci on 1q32 containing the complement regulatory protein-encoding genes CFH and CFHR1-5, with rs6677604 in CFH as the top single-nucleotide polymorphism and CFHR3-1 deletion (CFHR3-1∆) as the top signal for copy number variation. In this study, to explore the clinical effects of variation in CFH, CFHR3, and CFHR1 on IgAN susceptibility and progression, we enrolled two populations. Group 1 included 1178 subjects with IgAN and available genome-wide association study data. Group 2 included 365 subjects with IgAN and available clinical follow-up data. In group 1, rs6677604 was associated with mesangial C3 deposition by genotype-phenotype correlation analysis. In group 2, we detected a linkage between the rs6677604-A allele and CFHR3-1∆ and found that the rs6677604-A allele was associated with higher serum levels of CFH and lower levels of the complement activation split product C3a. Furthermore, CFH levels were positively associated with circulating C3 levels and negatively associated with mesangial C3 deposition. Moreover, serum levels of the pathogenic galactose-deficient glycoform of IgA1 were also associated with the degree of mesangial C3 deposition in patients with IgAN. Our findings suggest that genetic variants in CFH, CFHR3, and CFHR1 affect complement activation and thereby, predispose patients to develop IgAN.
Genetic polymorphisms in biotransformation enzymes in Crohn's disease: association with microsomal epoxide hydrolase
Authors: D J de Jong
Journal: Gut (2003)

<b>Background:</b> Mucosal biotransformation enzymes can modify toxic compounds in the gut. As chemical or oxidative stress may be involved in the aetiology of Crohn’s disease, genes encoding for enzymes involved in the prevention of such stress may be candidates for genetic susceptibility to Crohn’s disease. <b>Aim:</b> To assess the association of Crohn’s disease with genetic polymorphisms in cytochrome P450 1A1, glutathione S-transferases mu-1, pi-1, and theta-1, and epoxide hydrolase. <b>Methods:</b> χ<sup>2</sup> square analysis was used to compare frequencies of polymorphisms between 151 patients with Crohn’s disease and 149 healthy controls. <b>Results:</b> In patients, a genetic polymorphism in exon 3 of the microsomal epoxide hydrolase gene was distributed significantly different compared with controls (χ<sup>2</sup>=23.7; p&lt;0.0001). All other polymorphisms tested were equally distributed between patients and controls. <b>Conclusions:</b> Microsomal epoxide hydrolase may play a role in the pathophysiology of Crohn’s disease. Furthermore, the epoxide hydrolase gene is located on chromosome 1q, close to a region previously linked to Crohn’s disease.
Dysregulation of TGF-β activation contributes to pathogenesis in Marfan syndrome
Authors: Enid R. Neptune, Pamela A. Frischmeyer, Dan E. Arking, Loretha Myers, Tracie E. Bunton, Barbara Gayraud, Francesco Ramirez, Lynn Y. Sakai, Harry C. Dietz
Journal: Nature Genetics (2003)
Estimating Time to Conduct a Meta-analysis From Number of Citations Retrieved
Authors: I E Allen, I Olkin
Journal: JAMA (1999)

binomial distribution to compare 2 independent proportions.Two-tailed P values are reported for all comparisons.Results.Of the 407 participants who attended the 8 workshops, 355 baseline surveys were returned for data analysis (response rate, 87%).The response rate of the 407 participants for the 6-month follow-up was 77%.Physicians reported increased computer use daily or weekly (69% at baseline and 82% at follow-up; PϽ.001), Internet use (66% at baseline and 80% at follow-up; PϽ.002), and use of computers for e-mail access (PϽ.008) (TABLE).At follow-up, approximately half of respondents reported that learning the skills needed to access the Internet was easy, a rate un-changed from baseline.Type of Internet use did not change.Literature searches were the most common form of Internet use, followed by news retrieval.Comment.Our results suggest that physicians increase their Internet and e-mail use following attendance at a 4-hour Internet workshop.Nearly half continued to report that learning to use the Internet was easy once they have been taught the skills.Our study was limited by the self-reported data and lack of knowledge regarding whether the same sample responded on the first and second surveys.We also do not know whether physicians completing the workshops are similar to physicians overall.However, our study demonstrates that providing physicians the basic skills to access and use the Web can increase physicians' use of the Internet.
Roles of Radiotherapy and Chemotherapy in the Development of Contralateral Breast Cancer
Authors: Maartje J. Hooning, Berthe M.P. Aleman, Michael Hauptmann, Margreet H.A. Baaijens, Jan G.M. Klijn, Ruth Noyon, Marilyn Stovall, Flora E. van Leeuwen
Journal: Journal of Clinical Oncology (2008)

Few studies have examined whether modern radiotherapy and chemotherapy affect the risk of contralateral breast cancer (CBC), and results are inconclusive.We assessed long-term risk of CBC in a predominantly young breast cancer (BC) population (n = 7,221), focusing on the effects of radiation dose, chemotherapy, and family history of BC. Risk of CBC was evaluated using Cox proportional hazards regression models.Radiotherapy-associated risk of CBC increased with decreasing age at first treatment (age < 35 years, hazard ratio [HR] = 1.78; 95% CI, 0.85 to 3.72; age > 45 years, HR = 1.09; 95% CI, 0.82 to 1.45). Postmastectomy radiotherapy using direct electron fields led to a significantly lower radiation exposure to the contralateral breast than postlumpectomy radiotherapy using tangential fields. Women treated before age 45 years with postlumpectomy radiotherapy experienced 1.5-fold increased risk of CBC compared with those who had postmastectomy radiotherapy. The joint effects of postlumpectomy radiotherapy and strong family history for BC on risk of CBC were greater than expected when individual risks were summed (HR = 3.52; 95% CI, 2.07 to 6.02; P(departure from additivity) = .043). Treatment with adjuvant chemotherapy (cyclophosphamide, methotrexate, and fluorouracil) was associated with a nonsignificantly decreased risk of CBC in the first 5 years of follow-up but did not reduce CBC risk in subsequent years.Young patients with BC irradiated with breast tangentials experience increased risk of CBC, especially in those with a positive family history of BC. This finding should be taken into account when advising breast radiation with tangential fields to young patients with BC. Adjuvant chemotherapy seemed to reduce the risk of CBC during the first 5 years after treatment only.
Impairment of Visual Evoked Potentials
Authors: Tamás T. Várkonyi, Tünde Petõ, Rózsa Dégi, Katalin Keresztes, Csaba Lengyel, Márta Janáky, Péter Kempler, János Lonovics
Journal: Diabetes Care (2002)

Impairment of the central nervous system is a frequent complication of diabetes (1), but its clinical importance is still underestimated. The exact pathophysiology of the central nervous dysfunction is not clear, but it seems to be multifactorial, involving vascular and metabolic factors, similar to the pathogenesis of diabetic peripheral neuropathy (1). Earlier studies revealed new data on the central manifestations of diabetes but did not permit a comprehensive comparative analysis of the peripheral and central neuronal dysfunctions (2,3).

We recently observed significant correlations between the impairment of the auditory evoked potentials and the severity of autonomic and peripheral sensory neuropathy in type 1 diabetes (4). In addition to the detection of the auditory evoked potentials, evaluation of the visual evoked potentials furnishes another diagnostic tool for the assessment of functional anomalies of the cerebral function, even at an early stage of the pathogenetic process (2). The aim of this study was to demonstrate …
Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE)
Authors: J. Vestbo, W. Anderson, H. O. Coxson, C. Crim, F. Dawber, L. Edwards, G. Hagan, K. Knobil, D. A. Lomas, W. MacNee, E. K. Silverman, R. Tal-Singer
Journal: European Respiratory Journal (2008)

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and not well understood. The forced expiratory volume in one second is used for the diagnosis and staging of COPD, but there is wide acceptance that it is a crude measure and insensitive to change over shorter periods of time. Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) is a 3-yr longitudinal study with four specific aims: 1) definition of clinically relevant COPD subtypes; 2) identification of parameters that predict disease progression in these subtypes; 3) examination of biomarkers that correlate with COPD subtypes and may predict disease progression; and 4) identification of novel genetic factors and/or biomarkers that both correlate with clinically relevant COPD subtypes and predict disease progression. ECLIPSE plans to recruit 2,180 COPD subjects in Global Initiative for Chronic Obstructive Lung Disease categories II-IV and 343 smoking and 223 nonsmoking control subjects. Study procedures are to be performed at baseline, 3 months, 6 months and every 6 months thereafter. Assessments include pulmonary function measurements (spirometry, impulse oscillometry and plethysmography), chest computed tomography, biomarker measurement (in blood, sputum, urine and exhaled breath condensate), health outcomes, body impedance, resting oxygen saturation and 6-min walking distance. Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points is the largest study attempting to better describe the subtypes of chronic obstructive pulmonary disease, as well as defining predictive markers of its progression.
CaV2.3 calcium channels control second-phase insulin release
Authors: Xingjun Jing, Dai-Qing Li, Charlotta S. Olofsson, Albert Salehi, Vikas V. Surve, José Caballero, Rosita Ivarsson, Ingmar Lundquist, Alexey Pereverzev, Toni Schneider, Patrik Rorsman, Erik Renström
Journal: Journal of Clinical Investigation (2005)

Concerted activation of different voltage-gated Ca2+ channel isoforms may determine the kinetics of insulin release from pancreatic islets. Here we have elucidated the role of R-type CaV2.3 channels in that process. A 20% reduction in glucose-evoked insulin secretion was observed in CaV2.3-knockout (CaV2.3–/–) islets, close to the 17% inhibition by the R-type blocker SNX482 but much less than the 77% inhibition produced by the L-type Ca2+ channel antagonist isradipine. Dynamic insulin-release measurements revealed that genetic or pharmacological CaV2.3 ablation strongly suppressed second-phase secretion, whereas first-phase secretion was unaffected, a result also observed in vivo. Suppression of the second phase coincided with an 18% reduction in oscillatory Ca2+ signaling and a 25% reduction in granule recruitment after completion of the initial exocytotic burst in single CaV2.3–/– β cells. CaV2.3 ablation also impaired glucose-mediated suppression of glucagon secretion in isolated islets (27% versus 58% in WT), an effect associated with coexpression of insulin and glucagon in a fraction of the islet cells in the CaV2.3–/– mouse. We propose a specific role for CaV2.3 Ca2+ channels in second-phase insulin release, that of mediating the Ca2+ entry needed for replenishment of the releasable pool of granules as well as islet cell differentiation.
Nuclear Receptor Coactivators: Master Regulators of Human Health and Disease
Authors: Subhamoy Dasgupta, David M. Lonard, Bert W. O'Malley
Journal: Annual Review of Medicine (2013)

Transcriptional coregulators (coactivators and corepressors) have emerged as the principal modulators of the functions of nuclear receptors and other transcription factors. During the decade since the discovery of steroid receptor coactivator-1 (SRC-1), the first authentic coregulator, more than 400 coregulators have been identified and characterized, and deciphering their function has contributed significantly to our understanding of their role in human physiology. Deregulated expression of coregulators has been implicated in diverse disease states and related pathologies. The advancement of molecular technologies has enabled us to better characterize the molecular associations of the SRC family of coactivators with other protein complexes in the context of gene regulation. These continuing discoveries not only expand our knowledge of the roles of coactivators in various human diseases but allow us to discover novel coactivator-targeting strategies for therapeutic intervention in these diseases.
Helminth secretions induce de novo T cell Foxp3 expression and regulatory function through the TGF-β pathway
Authors: John R. Grainger, Katie A. Smith, James P. Hewitson, Henry J. McSorley, Yvonne Harcus, Kara J. Filbey, Constance A.M. Finney, Edward J.D. Greenwood, David P. Knox, Mark S. Wilson, Yasmine Belkaid, Alexander Y. Rudensky, Rick M. Maizels
Journal: The Journal of Experimental Medicine (2010)

Foxp3-expressing regulatory T (T reg) cells have been implicated in parasite-driven inhibition of host immunity during chronic infection. We addressed whether parasites can directly induce T reg cells. Foxp3 expression was stimulated in naive Foxp3− T cells in mice infected with the intestinal helminth Heligmosomoides polygyrus. In vitro, parasite-secreted proteins (termed H. polygyrus excretory-secretory antigen [HES]) induced de novo Foxp3 expression in fluorescence-sorted Foxp3− splenocytes from Foxp3–green fluorescent protein reporter mice. HES-induced T reg cells suppressed both in vitro effector cell proliferation and in vivo allergic airway inflammation. HES ligated the transforming growth factor (TGF) β receptor and promoted Smad2/3 phosphorylation. Foxp3 induction by HES was lost in dominant-negative TGF-βRII cells and was abolished by the TGF-β signaling inhibitor SB431542. This inhibitor also reduced worm burdens in H. polygyrus–infected mice. HES induced IL-17 in the presence of IL-6 but did not promote Th1 or Th2 development under any conditions. Importantly, antibody to mammalian TGF-β did not recognize HES, whereas antisera that inhibited HES did not affect TGF-β. Foxp3 was also induced by secreted products of Teladorsagia circumcincta, a related nematode which is widespread in ruminant animals. We have therefore identified a novel pathway through which helminth parasites may stimulate T reg cells, which is likely to be a key part of the parasite’s immunological relationship with the host.
Adaptive phenotypic plasticity: consensus and controversy
Authors: Sara Via, Richard Gomulkiewicz, Gerdien De Jong, Samuel M. Scheiner, Carl D. Schlichting, Peter H. Van Tienderen
Journal: Trends in Ecology & Evolution (1995)

Phenotypic plasticity is an environmentally based change in the phenotype. Understanding the evolution of adaptive phenotypic plasticity has been hampered by dissenting opinions on the merits of different methods of description, on the underlying genetic mechanisms, and on the way that plasticity is affected by natural selection in a heterogeneous environment. During much of this debate, the authors of this article have held opposing views. Here, we attempt to lay out current issues and summarize the areas of consensus and controversy surrounding the evolution of plasticity and the reaction norm (the set of phenotypes produced by a genotype over a range of environments).
Expression and cellular provenance of thymic stromal lymphopoietin and chemokines in patients with severe asthma and chronic obstructive pulmonary disease
Authors: S. Ying, B. O'Connor, J. Ratoff, Q. Meng, K. Mallett, D. Cousins, D. Robinson, G. Zhang, J. Zhao, T.H. Lee, C. Corrigan
Journal: Journal of Allergy and Clinical Immunology (2005)
Overweight is not a comorbidity factor during childhood asthma: the GrowthOb study
Authors: Bruno Mahut, Nicole Beydon, Christophe Delclaux
Journal: European Respiratory Journal (2011)

While being overweight is a risk factor for subsequent asthma in children, the importance of body mass index (BMI) as a comorbidity factor remains debated. The aim of this study was to assess the relationships between being overweight and the characteristics of childhood asthma. The BMI, BMI z-scores and International Obesity Task Force (IOTF) grades were evaluated in asthmatic children according to atopic status, symptoms during the past 3 months, exercise breathlessness, treatment and lung function in 6-15-yr-old children with confirmed asthma. 491 asthmatic children (mean ± SD age 10.8 ± 2.6 yrs; 179 females) were prospectively enrolled. There were 78 (15.5%) overweight (IOTF grade 1) and eight (1.6%) obese (grade 2) children. The children's BMI z-scores did not differ according to atopy, exacerbation, symptom-free days or treatment. The BMI z-score correlated positively with forced vital capacity and forced expiratory volume in 1 s in females, which could be related to earlier puberty in overweight females (growth spurt with increased volumes). Compared with normal weight children, overweight and obese children had reduced lung volume ratios (functional residual capacity/total lung capacity (TLC) and residual volume/TLC), no evidence of airflow limitation and similar symptoms. In conclusion, the observed functional relationships with BMI are not specific to asthma and being overweight is not associated with significant clinical impacts on asthma during childhood.
Phase 1 trial of irinotecan plus BCNU in patients with progressive or recurrent malignant glioma
Authors: Jennifer A. Quinn, David A. Reardon, Allan H. Friedman, Jeremy N. Rich, John H. Sampson, James Vredenburgh, Sridharan Gururangan, James M. Provenzale, Amy Walker, Holly Schweitzer, Darell D. Bigner, Sandra Tourt-Uhlig, James E. Herndon, Mary Lou Affronti, Susanne Jackson, Deborah Allen, Karen Ziegler, Cindy Bohlin, Christy Lentz, Henry S. Friedman
Journal: Neuro-Oncology (2004)

Irinotecan is a topoisomerase I inhibitor previously shown to be active in the treatment of malignant glioma. We now report the results of a phase 1 trial of irinotecan plus BCNU, or 1,3-bis(2-chloroethyl)-1-nitrosourea, for patients with recurrent or progressive MG. Irinotecan dose escalation occurred independently within 2 strata: patients receiving enzyme-inducing antiepileptic drugs (EIAEDs) and patients not receiving EIAEDs. BCNU was administered at a dose of 100 mg/m2 over 1 h every 6 weeks on the same day as the first irinotecan dose was administered. Irinotecan was administered intravenously over 90 min once weekly. Treatment cycles consisted of 4 weekly administrations of irinotecan followed by a 2-week rest with dose escalation in cohorts of 3 to 6 patients. Seventy-three patients were treated, including 49 patients who were on EIAEDs and 24 who were not on EIAEDs. The maximum tolerated dose for patients not on EIAEDs was 125 mg/m2. The maximum tolerated dose for patients on EIAEDs was 225 mg/m2. Dose-limiting toxicity was evenly distributed among the following organ systems: pulmonary, gastrointestinal, cardiovascular, neurologic, infectious, and hematologic, without a clear predominance of toxicity involving any one organ system. There was no evidence of increasing incidence of toxicity involving one organ system as irinotecan dose was escalated. On the basis of these results, we conclude that the recommended doses of irinotecan for a phase 2 clinical trial when given in combination with BCNU (100 mg/m2) are 225 mg/m2 for patients on EIAEDs and 125 mg/m2 for patients not on EIAEDs.