tbuckley/cabot-search huggingface dataset:
Lung Cancer Following Chemotherapy and Radiotherapy for Hodgkin's Disease
Authors: L. B. Travis
Journal: JNCI Journal of the National Cancer Institute (2002)

Background: Lung cancer is a frequent cause of death in patients cured of Hodgkin's disease, but the contributions of chemotherapy, radiotherapy, and smoking are not well described. We quantified the risk of treatment-associated lung cancer, taking into account tobacco use. Methods: Within a population-based cohort of 19 046 Hodgkin's disease patients (diagnosed from 1965 through 1994), a case–control study of lung cancer was conducted. The cumulative amount of cytotoxic drugs, the radiation dose to the specific location in the lung where cancer developed, and tobacco use were compared for 222 patients who developed lung cancer and for 444 matched control patients. All statistical tests were two-sided. Results: Treatment with alkylating agents without radiotherapy was associated with increased lung cancer risk (relative risk [RR] = 4.2; 95% confidence interval [CI] = 2.1 to 8.8), as was radiation dose of 5 Gy or more without alkylating agents (RR = 5.9; 95% CI = 2.7 to 13.5). Risk increased with both increasing number of cycles of alkylating agents and increasing radiation dose (P for trend <.001). Among patients treated with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP), risk increased with cumulative amounts of mechlorethamine and procarbazine (P<.001) when evaluated separately. Statistically significantly elevated risks of lung cancer were apparent within 1–4 years after treatment with alkylating agents, whereas excess risk after radiotherapy began 5 years after treatment and persisted for more than 20 years. Risk after treatment with alkylating agents and radiotherapy together was as expected if individual excess risks were summed. Tobacco use increased lung cancer risk more than 20-fold; risks from smoking appeared to multiply risks from treatment. Conclusions: Past treatments with alkylating agents and radiation therapy for Hodgkin's disease were associated with an increased risk of lung cancer in a dose-dependent and additive fashion. The precise risk estimates, however, should be interpreted cautiously, given the possible residual and enhancing effects of tobacco.
Targeting Cancer Cells With the Natural Compound Obtusaquinone
Authors: Christian E. Badr, Stephanie Van Hoppe, Hawasatu Dumbuya, Lee-Ann Tjon-Kon-Fat, Bakhos A. Tannous
Journal: JNCI Journal of the National Cancer Institute (2013)

Tumor cells present high levels of oxidative stress. Cancer therapeutics exploiting such biochemical changes by increasing reactive oxygen species (ROS) production or decreasing intracellular ROS scavengers could provide a powerful treatment strategy. To test the effect of our compound, obtusaquinone (OBT), we used several cell viability assays on seven different glioblastoma (GBM) cell lines and primary cells and on 12 different cell lines representing various cancer types in culture as well as on subcutaneous (n = 7 mice per group) and two intracranial GBM (n = 6–8 mice per group) and breast cancer (n = 6 mice per group) tumor models in vivo. Immunoblotting, immunostaining, flow cytometry, and biochemical assays were used to investigate the OBT mechanism of action. Histopathological analysis (n = 2 mice per group) and blood chemistry (n = 2 mice per group) were used to test for any compound-related toxicity. Statistical tests were two-sided. OBT induced rapid increase in intracellular ROS levels, downregulation of cellular glutathione levels and increase in its oxidized form, and activation of cellular stress pathways and DNA damage, subsequently leading to apoptosis. Oxidative stress is believed to be the main mechanism through which this compounds targets cancer cells. OBT was well tolerated in mice, slowed tumor growth, and statistically prolonged survival in GBM tumor models. The ratio of median survival in U251 intracranial model in OBT vs control was 1.367 (95% confidence interval [CI] of ratio = 1.031 to 1.367, P = .008). Tumor growth inhibition was also observed in a mouse breast cancer model (average tumor volume per mouse, OBT vs control: 36.3 vs 200.4mm3, difference = 164.1mm3, 95% CI =72.6 to 255.6mm3, P = .005). Given its properties and efficacy in cancer killing, our results suggest that OBT is a promising cancer therapeutic.
Stabilization of N-Myc Is a Critical Function of Aurora A in Human Neuroblastoma
Authors: Tobias Otto, Sebastian Horn, Markus Brockmann, Ursula Eilers, Lars Schüttrumpf, Nikita Popov, Anna Marie Kenney, Johannes H. Schulte, Roderick Beijersbergen, Holger Christiansen, Bernd Berwanger, Martin Eilers
Journal: Cancer Cell (2009)
Immunophenotyping of inflammatory cells in lesional skin of the extrinsic and intrinsic types of atopic dermatitis
Authors: N-K. Rho, W-S. Kim, D-Y. Lee, J-H. Lee, E-S. Lee, J-M. Yang
Journal: British Journal of Dermatology (2004)

Background There is a subgroup of atopic dermatitis (AD) patients with normal total and specific IgE levels and negative skin tests towards common allergens. This form of the disease has been referred to as the ‘intrinsic’ form of AD. Although previous studies have demonstrated differences in the cytokine profile between the extrinsic and intrinsic subtypes, the pathogenesis of both subtypes of AD remains unclear. Objectives To compare the inflammatory micromilieu in both forms of AD. Methods Immunophenotyping of the inflammatory cells was performed in lesional and nonlesional skin from 18 patients with extrinsic and 17 with intrinsic AD. Results Immunohistochemical analysis revealed a high proportion of CD4+ T cells in the dermis, with a similar CD4/CD8 ratio in the two groups. The expression levels of other T-cell markers and epidermal Langerhans cells were increased in both forms of AD. Although the T-cell repertoires in the two subtypes were similar, dermal infiltration of eosinophils and eosinophil granular proteins was more prominent in the extrinsic type than in the intrinsic type. Eotaxin immunoreactivity was also significantly higher in the extrinsic subtype. Conclusions The data suggest that although the overall inflammatory microenvironment in the two subtypes appears to be similar, differences in T-cell cytokine production might contribute to the differential tissue eosinophilia in these subtypes.
Inhibition of PI3K/mTOR Leads to Adaptive Resistance in Matrix-Attached Cancer Cells
Authors: Taru Muranen, Laura M. Selfors, Devin T. Worster, Marcin P. Iwanicki, Loling Song, Fabiana C. Morales, Sizhen Gao, Gordon B. Mills, Joan S. Brugge
Journal: Cancer Cell (2012)
Prediction of thrombo‐embolic risk in patients with hypertrophic cardiomyopathy (<scp>HCM</scp>Risk‐<scp>CVA</scp>)
Authors: Oliver P. Guttmann, Menelaos Pavlou, Constantinos O'Mahony, Lorenzo Monserrat, Aristides Anastasakis, Claudio Rapezzi, Elena Biagini, Juan Ramon Gimeno, Giuseppe Limongelli, Pablo Garcia‐Pavia, William J. McKenna, Rumana Z. Omar, Perry M. Elliott
Journal: European Journal of Heart Failure (2015)

Atrial fibrillation (AF) and thrombo-embolism (TE) are associated with reduced survival in hypertrophic cardiomyopathy (HCM), but the absolute risk of TE in patients with and without AF is unclear. The primary aim of this study was to derive and validate a model for estimating the risk of TE in HCM. Exploratory analyses were performed to determine predictors of TE, the performance of the CHA2 DS2 -VASc score, and outcome with vitamin K antagonists (VKAs).A retrospective, longitudinal cohort of seven institutions was used to develop multivariable Cox regression models fitted with pre-selected predictors. Bootstrapping was used for validation. Of 4821 HCM patients recruited between 1986 and 2008, 172 (3.6%) reached the primary endpoint of cerebrovascular accident (CVA), transient ischaemic attack (TIA), or systemic peripheral embolus within 10 years. A total of 27.5% of patients had a CHA2 DS2 -VASc score of 0, of whom 9.8% developed TE during follow-up. Cox regression revealed an association between TE and age, AF, the interaction between age and AF, TE prior to first evaluation, NYHA class, left atrial (LA) diameter, vascular disease, and maximal LV wall thickness. There was a curvilinear relationship between LA size and TE risk. The model predicted TE with a C-index of 0.75 [95% confidence interval (CI) 0.70-0.80] and the D-statistic was 1.30 (95% CI 1.05-1.56). VKA treatment was associated with a 54.8% (95% CI 31-97%, P = 0.037) relative risk reduction in HCM patients with AF.The study shows that the risk of TE in HCM patients can be identified using a small number of simple clinical features. LA size, in particular, should be monitored closely, and the assessment and treatment of conventional vascular risk factors should be routine practice in older patients. Exploratory analyses show for the first time evidence for a reduction of TE with VKA treatment. The CHA2 DS2 -VASc score does not appear to correlate well with the clinical outcome in patients with HCM and should not be used to assess TE risk in this population.
Genetic polymorphisms in themethylenetetrahydrofolate reductase andthymidylate synthase genes and risk of hepatocellular carcinoma
Authors: Jian-Min Yuan, Shelly C. Lu, David Van Den Berg, Sugantha Govindarajan, Zhen-Quan Zhang, Jose M. Mato, Mimi C. Yu
Journal: Hepatology (2007)

Methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TYMS) are known to play a role in DNA methylation, synthesis, and repair. The genetic mutations in MTHFR and TYMS genes may have influences on their respective enzyme activities. Data on the association studies of the MTHFR and TYMS genetic polymorphisms and risk of hepatocellular carcinoma (HCC) are sparse. MTHFR and TYMS genotypes were determined on 365 HCC cases and 457 healthy control subjects among Hispanic and non-Hispanic whites and African-Americans in Los Angeles County, California, and among Chinese in the city of Nanning, Guangxi, China. Relative to the high-activity genotype, each low-activity genotype of MTHFR was associated with a statistically nonsignificant 30% to 50% reduction in risk of HCC. Relative to the TYMS3′UTR +6/+6 genotype, individuals with 1 or 2 copies of the deletion allele had a statistically significant 50% reduction in risk of HCC. When we examined HCC risk by the total number of mutant alleles in the 3 polymorphic loci of MTHFR/TYMS (range, 0-4), there was a monotonic decrease in risk with increasing number of mutant alleles ( P for trend = 0.003). Individuals possessing the maximum number of mutant alleles ( i.e., 4) had an odds ratio of 0.46 (95% confidence interval = 0.23-0.93) for HCC compared with those with no or only 1 mutant allele. Conclusion: This study supports the hypothesis that reduced MTHFR activity and enhanced TYMS activity, both of which are essential elements in minimizing uracil misincorporation into DNA, may protect against the development of HCC. (Hepatology 2007.)
Effects of postprandial lipemia on plasma cholesterol metabolism.
Authors: G R Castro, C J Fielding
Journal: Journal of Clinical Investigation (1985)

Cholesterol net transport, esterification, and cholesteryl ester transfer have been determined in plasma during fasting, and postprandially, after a high fat-cholesterol meal. Significant rises in plasma triglyceride, phospholipid, and free cholesterol were associated with increases in cholesterol net transport, esterification, and transfer (all P less than 0.005), which were well correlated in individual subjects (r greater than 0.60). Essentially, the whole of free cholesterol required for such increased esterification was derived from cell membranes, when cultured fibroblasts were present, despite the increased level of free cholesterol in postprandial plasma; most of the additional cholesteryl ester generated was transferred to the low and very low density lipoproteins (LDL and VLDL) of plasma. Postprandial LDL (the major carrier of free and ester cholesterol and phospholipids among the acceptor lipoproteins) contained significantly decreased ratios of free cholesterol to phospholipid (P less than 0.001), which may modulate the increased transfer of cholesteryl ester to VLDL and LDL. These data suggest that the presence of postprandial acceptor lipoproteins in plasma may play an important role in stimulating the "reverse" transport of cholesterol from peripheral cells for hepatic degradation, which is effective even after the ingestion of dietary cholesterol.
Prognostic factors and outcomes in patients with leptomeningeal melanomatosis
Authors: Laura Harstad, Kenneth R. Hess, Morris D. Groves
Journal: Neuro-Oncology (2008)

The purpose of this study was to describe a cohort of patients with leptomeningeal melanomatosis (LM) and to determine prognostic factors for outcomes in these patients. The primary hypothesis was that more extensive burden of CNS metastasis at the time of diagnosis of LM (as evidenced by imaging of the CNS parenchyma and meninges and cerebrospinal fluid [CSF] cytology status [positive versus negative]) correlates with poorer outcomes. The records of all patients with LM treated at M. D. Anderson Cancer Center between 1944 and 2002 were reviewed. Information on clinical course and outcomes was gathered. Univariate and multivariate analyses were performed on 110 patients using Cox proportional hazards regression analysis to examine the effects of possible predictive factors on survival. The overall median survival from LM diagnosis was 10 weeks, with a 95% confidence interval (CI) of 8–14 weeks. Eighty-six (78.2%) patients had cutaneous primary lesions, and 23 (20.9%) had melanoma of unknown primary site. The primary hypothesis was not proven. Neither the presence of parenchymal CNS metastases, nor greater imaging evidence of LM, nor positive CSF cytology at diagnosis correlated with survival outcomes. Univariate analyses revealed possible predictors of longer survival, including the presence of supratentorial or spinal LM on imaging at diagnosis versus its absence and any treatment of LM, whereas elevated serum lactate dehydrogenase at the time of LM diagnosis predicted shorter survival. Multivariate analysis revealed that a history of a primary melanoma lesion originating on the trunk predicted shorter survival after LM diagnosis (hazard ratio [HR] = 2.0, 95% CI = 1.0–3.8, p = 0.035), and treatment with intrathecal chemotherapy predicted longer survival (HR = 0.5, 95% CI = 0.4–0.8, p = 0.0036). The positive result with respect to treatment is unreliable due to the inability to remove treatment selection bias from the analysis. This retrospective analysis confirmed the dismal prognosis associated with LM. The amount of CNS tumor burden at the time of diagnosis of LM did not inversely correlate with survival outcomes, contrary to our hypothesis.
Mutant cardiac ryanodine receptors and ventricular arrhythmias: is ?gain-of-function? obligatory?
Authors: A GOMEZ, S RICHARD
Journal: Cardiovascular Research (2004)

In this issue of Cardiovascular Research, Thomas et al.[1] evidence functional differences among sudden cardiac death (SCD)-linked ryanodine receptors (RyR 2 ) mutants.They challenge the conventional view that arrhythmogenic disorders associated with RyR 2 mutations result exclusively from dgain-of-functionT channelopathies generating aberrant spontaneous Ca 2+ release [2][3][4].Thomas et al. [1] now report a dloss-of-functionT phenotype of one RyR 2 mutant associated with SCD.
Trafficking and functional defects by mutations of the ATP-binding domains in MRP2 in patients with Dubin-Johnson syndrome
Authors: Kenkichi Hashimoto, Takeshi Uchiumi, Toshikazu Konno, Takuya Ebihara, Takanori Nakamura, Morimasa Wada, Shotaro Sakisaka, Fumio Maniwa, Teruo Amachi, Kazumitsu Ueda, Michihiko Kuwano
Journal: Hepatology (2002)

Dubin-Johnson syndrome (DJS) is a hereditary disease characterized by hyperbilirubinemia. We investigated the consequences of 2 missense mutations, R768W and Q1382R, of nucleotide-binding domains (NBDs) of the multidrug resistance protein 2 (MRP2; ABCC2) that were previously identified in patients with DJS. Pulse chase analysis revealed that the precursor form of the wild-type and Q1382R MRP2 were converted to the mature form, which is resistant to endoglycosidase H (Endo H) in about 60 minutes. However, the precursor form of the R768W MRP2, which is sensitive to endoglycosidase H, was degraded within 120 minutes and did not mature to the fully glycosylated form. Proteasome inhibitors inhibited the degradation of the precursor form of the R768W MRP2. Unlike the R768W MRP2, the Q1382R MRP2 was mainly localized on the apical membrane in the wild-type form. However, efflux of glutathione monochlorobimane (GS-MCLB) and ATP-dependent leukotriene C 4 (LTC 4 ) uptake into plasma membrane vesicles from cells expressing the Q1382R MRP2 were markedly reduced, suggesting that the Q1382R MRP2 on the apical membrane was nonfunctional. Vanadate-induced nucleotide trapping with 8-azido-[α-32P]ATP in the wild-type MRP2 was stimulated by estradiol glucuronide (E 2 17βG) in a concentration-dependent manner but that in the Q1382R MRP2 was not. In conclusion, the R768W mutation causes deficient maturation and impaired sorting, and the Q1382R mutation does not affect maturation or sorting but impairs the substrate-induced ATP hydrolysis.
NIFEDIPINE FOR RAYNAUD'S PHENOMENON
Authors: M.H.A. Rustin, E.D. Cooke, S.A. Bowcock, J.D.T. Kirby, P. Bravard, N. Moore, A. Kahan, S. Weber, B. Amor, C.J. Menkes, L. Saporta, M. Hodara, M. Degeorges
Journal: The Lancet (1983)
Immune response to varicella vaccine in children with atopic dermatitis compared with nonatopic controls
Authors: Lynda Schneider, Adriana Weinberg, Mark Boguniewicz, Patricia Taylor, Hans Oettgen, Lisa Heughan, Daniel Zaccaro, Brian Armstrong, Aaron Holliday, Donald Y.M. Leung
Journal: Journal of Allergy and Clinical Immunology (2010)
The outcomes of juvenile idiopathic arthritis in children managed with contemporary treatments: results from the ReACCh-Out cohort
Authors: Jaime Guzman, Kiem Oen, Lori B Tucker, Adam M Huber, Natalie Shiff, Gilles Boire, Rosie Scuccimarri, Roberta Berard, Shirley M L Tse, Kimberly Morishita, Elizabeth Stringer, Nicole Johnson, Deborah M Levy, Karen Watanabe Duffy, David A Cabral, Alan M Rosenberg, Maggie Larché, Paul Dancey, Ross E Petty, Ronald M Laxer, Earl Silverman, Paivi Miettunen, Anne-Laure Chetaille, Elie Haddad, Kristin Houghton, Lynn Spiegel, Stuart E Turvey, Heinrike Schmeling, Bianca Lang, Janet Ellsworth, Suzanne Ramsey, Alessandra Bruns, Sarah Campillo, Susanne Benseler, Gaëlle Chédeville, Rayfel Schneider, Rae Yeung, Ciarán M Duffy, Roxana Bolaria, Katherine Gross, Brian Feldman, Debbie Feldman, Bonnie Cameron, Roman Jurencak, Johannes Roth, Jean Dorval, Claire LeBlanc, Claire St. Cyr
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objective</h3> To describe clinical outcomes of juvenile idiopathic arthritis (JIA) in a prospective inception cohort of children managed with contemporary treatments. <h3>Methods</h3> Children newly diagnosed with JIA at 16 Canadian paediatric rheumatology centres from 2005 to 2010 were included. Kaplan–Meier survival curves for each JIA category were used to estimate probability of ever attaining an active joint count of 0, inactive disease (no active joints, no extraarticular manifestations and a physician global assessment of disease activity &lt;10 mm), disease remission (inactive disease &gt;12 months after discontinuing treatment) and of receiving specific treatments. <h3>Results</h3> In a cohort of 1104 children, the probabilities of attaining an active joint count of 0 exceeded 78% within 2 years in all JIA categories. The probability of attaining inactive disease exceeded 70% within 2 years in all categories, except for RF-positive polyarthritis (48%). The probability of discontinuing treatment at least once was 67% within 5 years. The probability of attaining remission within 5 years was 46–57% across JIA categories except for polyarthritis (0% RF-positive, 14% RF-negative). Initial treatment included joint injections and non-steroidal anti-inflammatory drugs for oligoarthritis, disease-modifying antirheumatic drugs (DMARDs) for polyarthritis and systemic corticosteroids for systemic JIA. <h3>Conclusions</h3> Most children with JIA managed with contemporary treatments attain inactive disease within 2 years of diagnosis and many are able to discontinue treatment. The probability of attaining remission within 5 years of diagnosis is about 50%, except for children with polyarthritis.
Computed tomography features of liparitosis: a pneumoconiosis due to amorphous silica
Authors: S. Mazziotti, M. Gaeta, C. Costa, G. Ascenti, L. Barbaro Martino, G. Spatari, N. Settineri, M. Barbaro
Journal: European Respiratory Journal (2004)

The purpose of this study was to describe the radiological features of pleural, parenchymal and mediastinal damage due to occupational inhalation of pumice. In total, 31 workers were evaluated for annual follow-up. Spiral computed tomography (CT) was obtained in the three patients with evident parenchymal abnormalities at chest radiograph. High-resolution computed tomography (HRCT) was performed in the remaining 28 subjects with no radiographical evidence of pleuro-pulmonary damage or evidence of pleural plaques, in order to exclude parenchymal involvement. Pumice samples were analysed by radiograph diffraction and scanning electron microscopy. Spiral CT showed parahilar conglomerate masses containing fine reticular calcifications in three of 31 (9.7%) patients. HRCT showed several bilateral pleural plaques, without any parenchymal lesion in eight of 28 (28.6%) cases. Statistical analysis indicated correlation between CT findings and pulmonary function, as well as exposure to pumice. The analysis of pumice excluded the presence of asbestos. The findings from this study suggest that pleural plaque may be the only sign of disease in patients with a history of pumice inhalation. However, conglomerate parahilar masses are probably due to exposure to massive amounts of heated pumice, and seem to have different pathogenesis and histopathological characteristics to silicosis.