tbuckley/cabot-search huggingface dataset:
Genome-wide search for atopy susceptibility genes in Dutch families with asthma
Authors: Gerard H. Koppelman, O.Colin Stine, Jianfeng Xu, Timothy D. Howard, Siqun L. Zheng, Henk F. Kauffman, Eugene R. Bleecker, Deborah A. Meyers, Dirkje S. Postma
Journal: Journal of Allergy and Clinical Immunology (2002)
eNOS uncoupling in pulmonary hypertension
Authors: L. V. d'Uscio
Journal: Cardiovascular Research (2011)

This editorial refers to ‘Pulmonary hypertension in adult Alk1 heterozygous mice due to oxidative stress’ by M. Jerkic et al. , pp. 375–384, this issue. 

Pulmonary arterial hypertension (PAH) is characterized by high blood pressure and vascular remodelling in pulmonary arteries and subsequently right ventricular hypertrophy. Although several studies in animal models of pulmonary hypertension (PH) and pathological examinations of lung tissue obtained from PAH patients show occlusion of pulmonary arteries, the exact molecular mechanisms for vascular abnormalities remain unclear.1 Endothelial dysfunction seems to be one of the earliest events in PAH and is characterized by reduced levels of vasodilators nitric oxide (NO) and prostacyclin and increased vasoconstrictor agents, such as endothelin-1 and prostanoids.1 NO formed from L-arginine by endothelial nitric oxide synthase (eNOS) plays an important protective role in vascular haemostasis.2

Activin receptor-like kinase 1 (Alk1) is a type I receptor of transforming growth factor-beta family proteins or bone morphogenic proteins and is mainly expressed in endothelial cells, regulating proliferation and migration in vitro and angiogenesis in vivo .3,4 Mutation of the Alk1 gene causes hereditary haemorrhagic telangiectasia type II in patients, an autosomal dominant vascular dysplasia that results …
T helper cell polarisation in coeliac disease: any (T-)bet ?
Authors: M H Holtmann
Journal: Gut (2004)

Recent data strongly support the view that coeliac disease is a Th1 mediated inflammatory disease as both interferon γ production and T-bet levels in gut infiltrating cells are upregulated

The puzzling observation on high interferon γ (IFN-γ) but low interleukin (IL)-12 levels in coeliac disease (CD) has resulted in questions about the underlying principles of T helper cell polarisation. In this issue of G ut ,1 the molecular basis of T helper cell polarisation in CD has been illuminated by the finding that T-bet, the master transcription factor of T helper cell type 1 (Th1) cells, is upregulated in this disease [see page 1090] .

The past decade has witnessed a dramatic improvement in our pathophysiological understanding of inflammatory disorders of the intestinum due to extensive research efforts focusing on regulatory mechanisms of the immune system. This has been greatly facilitated by the advent of molecular biological techniques which have allowed for the identification and characterisation of distinct factors in the complex regulatory network of the immune system. General themes have thus been recognised and an attempt is being made to classify diseases according to common immunological features.

One crucial emerging theme is the Th1/Th2 polarisation of T helper cells.2,3 On activation with distinct immunological stimuli, naive CD4+ precursor T helper cells differentiate into mature T cells which either produce a so called Th1 cytokine profile characterised by tumour necrosis factor α (TNF-α) and IFN-γ, or a T helper cell type 2 (Th2) cytokine profile including IL-4, IL-5, IL-9, and IL-13. While these T cell subsets produce proinflammatory cytokines that can cause substantial tissue injury in vivo, more recent data suggest that additional subsets of CD4+ T helper cells exist with anti-inflammatory functions. These subsets include T helper 3 (Th3) cells producing transforming growth …
CD4+ T cells cause multinucleated giant cells to form around Cryptococcus neoformans and confine the yeast within the primary site of infection in the respiratory tract.
Authors: J O Hill
Journal: The Journal of Experimental Medicine (1992)

The possible mechanisms by which CD4+ T cells prevent the dissemination of Cryptococcus neoformans from the primary site of infection in the respiratory tract were examined. It was found that even before fungicidal mechanisms are fully induced in the lungs, the host generates a CD4+ T cell-dependent inflammatory response that sequesters yeast within the pulmonary alveoli. This confinement is evident histopathologically and demonstrable objectively as a rapid decline in the ability to dislodge yeast from the lungs by bronchopulmonary lavage. One striking component of this response is the enclosure of cryptococci within multinucleated giant cells in granulomas. Studies in severe combined immunodeficient mice that were engrafted with selected lymphocyte subpopulations show that B cells, and hence anti-Cryptococcus antibodies, are not necessary for the CD4+ T cell-dependent responses that isolate and subsequently destroy this opportunistic pathogen in the lung parenchyma.
Echoing the call to move “beyond prejudice” in search of intergroup equality
Authors: Stephen C. Wright, Lisa M. Bitacola
Journal: Behavioral and Brain Sciences (2012)

Abstract We also critique the myopic focus on prejudice reduction, but we do not support the call for a reconceptualization of prejudice. Redefining key psychological constructs is unproductive. Also, we point to interpersonal dynamics in cross-group interaction as a key mechanism in the prejudice reduction/collective action paradox and point to solutions involving intrapersonal/interpersonal processes, as well as broader structural intergroup relations.
The impact of injecting networks on hepatitis C transmission and treatment in people who inject drugs
Authors: Margaret Hellard, David A Rolls, Rachel Sacks‐Davis, Garry Robins, Philippa Pattison, Peter Higgs, Campbell Aitken, Emma McBryde
Journal: Hepatology (2014)

With the development of new highly efficacious direct-acting antiviral (DAA) treatments for hepatitis C virus (HCV), the concept of treatment as prevention is gaining credence. To date, the majority of mathematical models assume perfect mixing, with injectors having equal contact with all other injectors. This article explores how using a networks-based approach to treat people who inject drugs (PWID) with DAAs affects HCV prevalence. Using observational data, we parameterized an exponential random graph model containing 524 nodes. We simulated transmission of HCV through this network using a discrete time, stochastic transmission model. The effect of five treatment strategies on the prevalence of HCV was investigated; two of these strategies were (1) treat randomly selected nodes and (2) "treat your friends," where an individual is chosen at random for treatment and all their infected neighbors are treated. As treatment coverage increases, HCV prevalence at 10 years reduces for both the high- and low-efficacy treatment. Within each set of parameters, the treat your friends strategy performed better than the random strategy being most marked for higher-efficacy treatment. For example, over 10 years of treating 25 per 1,000 PWID, the prevalence drops from 50% to 40% for the random strategy and to 33% for the treat your friends strategy (6.5% difference; 95% confidence interval: 5.1-8.1).Treat your friends is a feasible means of utilizing network strategies to improve treatment efficiency. In an era of highly efficacious and highly tolerable treatment, such an approach will benefit not just the individual, but also the community more broadly by reducing the prevalence of HCV among PWID.
GenoType MTBDR<i>sl</i>performance on clinical samples with diverse genetic background
Authors: Paolo Miotto, Andrea M. Cabibbe, Paola Mantegani, Emanuele Borroni, Lanfranco Fattorini, Enrico Tortoli, Giovanni B. Migliori, Daniela M. Cirillo
Journal: European Respiratory Journal (2012)

We evaluate the performance of the GenoType® MTBDR sl (Hain Lifescience Nehren, Germany) for the detection of second-line resistant tuberculosis and we correlate the frequency of mutations to different Mycobacterium tuberculosis genotypes. We tested 175 strains and 59 clinical specimens interpreting the results according to the Standards for Reporting of Diagnostic Accuracy recommendations. All the strains were also investigated by spoligotyping and Mycobacterial Interspersed Repetitive Units–Variable Number of Tandem Repeats typing. The performances of the MTBDR sl in detecting resistance to fluoroquinolones (FQ), second-line injectable drugs (SLID), and ethambutol (EMB) on clinical isolates were similar (specificity ∼99%, sensitivity ∼70%, and positive predictive value (PPV) ∼99%). Of the 59 respiratory specimens, three samples were classified as “indeterminate”. The specificity in detecting resistances was similar for FQs and EMB 100% (95% CI 92.7–100%) and 100% (95% CI 83.9–100%), respectively with a PPV of 100% (95% CI 64.6–100%) and 100% (95% CI 87.9–100%), respectively. Detection of SLID showed a specificity of 89.1% (95% CI 77.0–95.3%) and a PPV of 58.3% (95% CI 32.0–80.7%). Sensitivity for FQ-resistance detection was 100% (95% CI 64.6–100%), whereas for SLID and EMB it was 89.1% (95% CI 77.0-95.3%) and 86.1% (95% CI 71.3-93.9%), respectively. We detected a significant association between mutations in the rrs gene and Beijing lineage. The MTBDR sl can be used to “rule in” extensively drug-resistant strains of tuberculosis in a high risk group; the low sensitivity and negative predicted value (NPV) make confirmation by conventional drug susceptibility testing mandatory when mutations are not identified. NPV for SLID is higher in Beijing strains, showing that the predictive values of the molecular tests are related to the genetic background.
The LxCxE pRb Interaction Domain of Cyclin D1 Is Dispensable for Murine Development
Authors: Mark W. Landis, Nelson E. Brown, Gregory L. Baker, Anna Shifrin, Manjusri Das, Yan Geng, Piotr Sicinski, Philip W. Hinds
Journal: Cancer Research (2007)

Abstract Cyclin D1 is a multifunctional, tumor-associated protein that interacts with pRb via a conserved LxCxE motif, activates a kinase partner, directs the phosphorylation of pRb, activates cyclin E–cyclin-dependent kinase 2 (cdk2) by titrating Cip/Kip cdk inhibitors, and modulates the activity of a variety of transcription factors. It is thought that some of the proproliferative function of cyclin D1 is exerted by LxCxE-dependent binding to the pRb pocket domain, which might interfere with the ability of pRb to repress transcription by recruiting cellular chromatin remodeling proteins to E2F-dependent promoters. To test the importance of the LxCxE domain in vivo, we have generated a “knock-in” mouse by replacing the wild-type cyclin D1 gene with a mutant allele precisely lacking the nucleotides encoding the LxCxE domain. Analysis of this mouse has shown that the LxCxE protein is biochemically similar to wild-type cyclin D1 in all tested respects. Moreover, we were unable to detect abnormalities in growth, retinal development, mammary gland development, or tumorigenesis, all of which are affected by deleting cyclin D1. Although we cannot exclude the presence of subtle defects, these results suggest that the LxCxE domain of cyclin D1 is not necessary for function despite the absolute conservation of this motif in the D-type cyclins from plants and vertebrates. [Cancer Res 2007;67(16):7613–9]
Detection and treatment of testicular cancer
Authors: J. P. Richie
Journal: CA A Cancer Journal for Clinicians (1993)

The survival rate for testicular cancer has undergone a dramatic increase from 10 percent in the 1970s to 90 percent in the 1990s. This increase is due to improvements in clinical practice that have now made testicular cancer one of the most curable solid tumors. This article overviews the detection and treatment of testicular cancer, as well as its histology, epidemiology, and natural history.
Recognition of a New Chemotherapeutic Vesicant: Trabectedin (Ecteinascidin-743) Extravasation With Skin and Soft Tissue Damage
Authors: Todd A. Theman, Tristan L. Hartzell, Indranil Sinha, Kathleen Polson, Jeffrey Morgan, George D. Demetri, Dennis P. Orgill, Suzanne George
Journal: Journal of Clinical Oncology (2009)
Multiple Fractures With Pseudoaneurysm Formation in a Subclavian Artery Stent
Authors: Ravi S. Math, Ravindranath Khandenahally Shankarappa, Ramesh Dwarakaprasad, Satish Karur, Shivakumar Bhairappa, Praveen Jayan J.P., Cholenahally Nanjappa Manjunath
Journal: Circulation (2011)
Adenoviral E1A Targets Mdm4 to Stabilize Tumor Suppressor p53
Authors: Zheng Li, Chi-Ping Day, Jer-Yen Yang, Wen-Bin Tsai, Guillermina Lozano, Hsiu-Ming Shih, Mien-Chie Hung
Journal: Cancer Research (2004)

Abstract The adenoviral protein E1A associates with multiple anticancer activities, including stabilization of p53 tumor suppressor, and has been tested through gene therapy approaches in clinical trials. To identify potential E1A-binding proteins involved in E1A’s anticancer activities, we screened a yeast two-hybrid library and identified Mdm4, an Mdm2-related p53-binding protein, as a novel E1A-binding protein. The NH2-terminal region of Mdm4 and the CR1 domain of E1A were required for the interaction between E1A and Mdm4. E1A preferentially bound to Mdm4 rather than Mdm2 and formed a complex with p53 in the presence of Mdm4, resulting in the stabilization of p53 in a p14ARF-independent manner. E1A failed to stabilize p53 in the absence of Mdm4, showing that Mdm4 was required for p53 stabilization by E1A. Moreover, E1A-mediated stabilization of p53 occurred in nucleus. Although it had no effect on the p53-Mdm2 interaction, E1A facilitated Mdm4 binding to p53 and inhibited Mdm2 binding to Mdm4, resulting in decreased nuclear exportation of p53. Thus, our findings highlighted a novel mechanism, whereby E1A stabilized the p53 tumor suppressor through Mdm4.
Phagolysosome formation in normal and colchicine-treated macrophages.
Authors: E L Pesanti, S G Axline
Journal: The Journal of Experimental Medicine (1975)

Intracellular lysosomal fusion has been evaluated in cultivated mouse peritoneal macrophages by measurement of transfer of acid phosphatase to polyvinyltoluene (PVT)-containing phagolysosomes. Enzyme transfer was found to be directly and significantly related to the uptake of PVT and to be independent of time allowed for phagolysosome formation over time periods of 15 min to 18 h. In addition, the extent of transfer of lysosomal enzyme to phagolysosomes was unaffected by treatment of the cells with 10(-6) M colchicine, a dose which eradicates morphologically identifiable microtubules in this cell type within 2 h. The data indicate that intracellular fusion of lysosomes with phagosomes in the macrophage does not require formed microtubules and suggest that fusion occurs promptly after interiorization of inert particles.
Changes in DNA Methylation Patterns in Subjects Exposed to Low-Dose Benzene
Authors: Valentina Bollati, Andrea Baccarelli, Lifang Hou, Matteo Bonzini, Silvia Fustinoni, Domenico Cavallo, Hyang-Min Byun, Jiayi Jiang, Barbara Marinelli, Angela C. Pesatori, Pier A. Bertazzi, Allen S. Yang
Journal: Cancer Research (2007)

Aberrant DNA methylation patterns, including global hypomethylation, gene-specific hypermethylation/hypomethylation, and loss of imprinting (LOI), are common in acute myelogenous leukemia (AML) and other cancer tissues. We investigated for the first time whether such epigenetic changes are induced in healthy subjects by low-level exposure to benzene, a widespread pollutant associated with AML risk. Blood DNA samples and exposure data were obtained from subjects with different levels of benzene exposure, including 78 gas station attendants, 77 traffic police officers, and 58 unexposed referents in Milan, Italy (personal airborne benzene range, < 6-478 microg/m(3)). Bisulfite-PCR pyrosequencing was used to quantitate DNA methylation in long interspersed nuclear element-1 (LINE-1) and AluI repetitive elements as a surrogate of genome-wide methylation and examine gene-specific methylation of MAGE-1 and p15. Allele-specific pyrosequencing of the H19 gene was used to detect LOI in 96 subjects heterozygous for the H19 imprinting center G/A single-nucleotide polymorphism. Airborne benzene was associated with a significant reduction in LINE-1 (-2.33% for a 10-fold increase in airborne benzene levels; P = 0.009) and AluI (-1.00%; P = 0.027) methylation. Hypermethylation in p15 (+0.35%; P = 0.018) and hypomethylation in MAGE-1 (-0.49%; P = 0.049) were associated with increasing airborne benzene levels. LOI was found only in exposed subjects (4 of 73, 5.5%) and not in referents (0 of 23, 0.0%). However, LOI was not significantly associated with airborne benzene (P > 0.20). This is the first human study to link altered DNA methylation, reproducing the aberrant epigenetic patterns found in malignant cells, to low-level carcinogen exposure.
An SREBP-Responsive microRNA Operon Contributes to a Regulatory Loop for Intracellular Lipid Homeostasis
Authors: Tae-Il Jeon, Ryan M. Esquejo, Manuel Roqueta-Rivera, Peter E. Phelan, Young-Ah Moon, Subramaniam S. Govindarajan, Christine C. Esau, Timothy F. Osborne
Journal: Cell Metabolism (2013)
ZIP4 is a novel molecular marker for glioma
Authors: Y. Lin, Y. Chen, Y. Wang, J. Yang, V. F. Zhu, Y. Liu, X. Cui, L. Chen, W. Yan, T. Jiang, G. W. Hergenroeder, S. A. Fletcher, J. M. Levine, D. H. Kim, N. Tandon, J.-J. Zhu, M. Li
Journal: Neuro-Oncology (2013)

Dysregulated zinc transport has been observed in many cancers. However, the status of zinc homeostasis and the expression profile of zinc transporters in brain and brain tumors have not been reported. The gene profiles of 14 zinc importers (ZIPs) and 10 zinc exporters (ZnTs) in patients with glioma were studied by investigating the association between the zinc transporters and brain tumor characteristics (tumor grade and overall survival time). Three independent cohorts were analyzed to cross-validate the findings: the Chinese Glioma Genome Atlas (CGCA) cohort (n = 186), the US National Cancer Institute Repository for Molecular Brain Neoplasia Data (REMBRANDT) cohort (n = 335), and The University of Texas (UT) cohort (n = 34). The expression of ZIP3, 4, 8, 14, ZnT5, 6, and 7 were increased, and the expression of ZnT10 was decreased in grade IV gliomas, compared with grade II gliomas. Among all 24 zinc transporters, ZIP4 is most significantly associated with tumor grade and overall survival; this finding is consistent across 2 independent cohorts (CGCA and REMBRANDT) and is partially validated by the third cohort (UT). High ZIP4 expression was significantly associated with higher grade of gliomas and shorter overall survival (hazard ratio = 1.61, 95% confidence interval = 1.02–2.53, P = .040 in CGCA cohort; hazard ratio = 1.32, 95% confidence interval = 1.08–1.61, P = .007 in REMBRANDT cohort). Dysregulated expression of zinc transporters is involved in the progression of gliomas. Our results suggest that ZIP4 may serve as a potential diagnostic and prognostic marker for gliomas.
Prospective Study on Incidence, Risk Factors, and Long-Term Outcome of Osteonecrosis in Pediatric Acute Lymphoblastic Leukemia
Authors: Mariël L. te Winkel, Rob Pieters, Wim C.J. Hop, Hester A. de Groot-Kruseman, Maarten H. Lequin, Inge M. van der Sluis, Jos P.M. Bökkerink, Jan A. Leeuw, Marrie C.A. Bruin, R. Maarten Egeler, Anjo J.P. Veerman, Marry M. van den Heuvel-Eibrink
Journal: Journal of Clinical Oncology (2011)

We studied cumulative incidence, risk factors, therapeutic strategies, and outcome of symptomatic osteonecrosis in pediatric patients with acute lymphoblastic leukemia (ALL).Cumulative incidence of osteonecrosis was assessed prospectively in 694 patients treated with the dexamethasone-based Dutch Child Oncology Group-ALL9 protocol. Osteonecrosis was defined by development of symptoms (National Cancer Institute grade 2 to 4) during treatment or within 1 year after treatment discontinuation, confirmed by magnetic resonance imaging. We evaluated risk factors for osteonecrosis using logistic multivariate regression. To describe outcome, we reviewed clinical and radiologic information after antileukemic treatment 1 year or more after osteonecrosis diagnosis.Cumulative incidence of osteonecrosis at 3 years was 6.1%. After adjustment for treatment center, logistic multivariate regression identified age (odds ratio [OR], 1.47; P < .01) and female sex (OR, 2.23; P = .04) as independent risk factors. Median age at diagnosis of ALL in patients with osteonecrosis was 13.5 years, compared with 4.7 years in those without. In 21 (55%) of 38 patients with osteonecrosis, chemotherapy was adjusted. Seven patients (18%) underwent surgery: five joint-preserving procedures and two total-hip arthroplasties. Clinical follow-up of 35 patients was evaluated; median follow-up was 4.9 years. In 14 patients (40%), symptoms completely resolved; 14 (40%) had symptoms interfering with function but not with activities of daily living (ADLs; grade 2); seven (20%) had symptoms interfering with ADLs (grade 3). In 24 patients, radiologic follow-up was available; in six (25%), lesions improved/disappeared; in 13 (54%), lesions remained stable; five (21%) had progressive lesions.Six percent of pediatric patients with ALL developed symptomatic osteonecrosis during or shortly after treatment. Older age and female sex were risk factors. After a median follow-up of 5 years, 60% of patients had persistent symptoms.