tbuckley/cabot-search huggingface dataset:
Randomized Phase II Study of Pemetrexed, Carboplatin, and Thoracic Radiation With or Without Cetuximab in Patients With Locally Advanced Unresectable Non–Small-Cell Lung Cancer: Cancer and Leukemia Group B Trial 30407
Authors: Ramaswamy Govindan, Jeffrey Bogart, Thomas Stinchcombe, Xiaofei Wang, Lydia Hodgson, Robert Kratzke, Jennifer Garst, Timothy Brotherton, Everett E. Vokes
Journal: Journal of Clinical Oncology (2011)

Purpose Cancer and Leukemia Group B conducted a randomized phase II trial to investigate two novel chemotherapy regimens in combination with concurrent thoracic radiation therapy (TRT). Patients and Methods Patients with unresectable stage III non–small-cell lung cancer (NSCLC) were randomly assigned to carboplatin (area under the curve, 5) and pemetrexed (500 mg/m 2 ) every 21 days for four cycles and TRT (70 Gy; arm A) or the same treatment with cetuximab administered concurrent only with TRT (arm B). Patients in both arms received up to four cycles of pemetrexed as consolidation therapy. The primary end point was the 18-month overall survival (OS) rate; if the 18-month OS rate was ≥ 55%, the regimen(s) would be considered for further study. Results Of the 101 eligible patients enrolled (48 in arm A and 53 in arm B), 60% were male; the median age was 66 years (range, 32 to 81 years); 44% and 35% had adenocarcinoma and squamous carcinoma, respectively; and more patients enrolled onto arm A compared with arm B had a performance status of 0 (58% v 34%, respectively; P = .04). The 18-month OS rate was 58% (95% CI, 46% to 74%) in arm A and 54% (95% CI, 42% to 70%) in arm B. No significant difference in OS between patients with squamous and nonsquamous NSCLC was observed (P = .667). The toxicities observed were consistent with toxicities associated with concurrent chemoradiotherapy. Conclusion The combination of pemetrexed, carboplatin, and TRT met the prespecified criteria for further evaluation. This regimen should be studied further in patients with locally advanced unresectable nonsquamous NSCLC.
MicroRNAs Involved in Molecular Circuitries Relevant for the Duchenne Muscular Dystrophy Pathogenesis Are Controlled by the Dystrophin/nNOS Pathway
Authors: Davide Cacchiarelli, Julie Martone, Erika Girardi, Marcella Cesana, Tania Incitti, Mariangela Morlando, Carmine Nicoletti, Tiziana Santini, Olga Sthandier, Laura Barberi, Alberto Auricchio, Antonio Musarò, Irene Bozzoni
Journal: Cell Metabolism (2010)
Winter mortality modifies the heat-mortality association the following summer
Authors: J. Rocklöv, B. Forsberg, K. Meister
Journal: European Respiratory Journal (2008)

The present study aimed to investigate how the heat-related increase in deaths in summer and the extent of mortality displacement depend on influenza and other categories of mortality in the previous winter, which when low leaves a greater pool of susceptible individuals. Mortality data from Stockholm, Sweden, from 1990–2002 were stratified into a summer period and a winter period. A Poisson regression model was established for the daily mortality in the summer, with temperature and confounders as explanatory variables. In addition, indicators of total, respiratory, cardiovascular and influenza mortality of the winter period were incorporated as effect modifiers in the summer model, and lagged effects in strata defined by indicators were studied. A high rate of respiratory as well as cardiovascular mortality in winter reduced the heat effect the following summer, and influenza mortality tended to do so as well. The cumulative effect per °C increase was 0.95% below and 0.89% above a threshold (21.3°C) after a winter with low cardiovascular and respiratory mortality, but -0.23% below and 0.21% above the threshold after a winter with high cardiovascular and respiratory mortality. The current study shows that high respiratory, cardiovascular and influenza mortality in winter leads to lower temperature effects in the following summer. It also suggests that persons for whom influenza may be fatal are often also susceptible to heat and this subgroup might, therefore, not benefit as much as expected from influenza vaccinations.
Computed tomography for diagnosis of hepatic rupture in primary systemic amyloidosis
Authors: Dennis A. Gastineau, Morie A. Gertz, Charles B. Rosen, Robert A. Kyle
Journal: American Journal of Hematology (1991)

Abstract Hepatic rupture in primary systemic amyloidosis is extremely ominous; death occurs in hours to days. We present two cases of hepatic rupture diagnosed ante mortem with computed tomography (CT). Surgical repair was possible in one instance and successfully controlled the bleeding. In the setting of primary amyloidosis, the early use of CT scanning for undiagnosed ascites, hypotension, or rapid organ enlargement may lead to early diagnosis and potential surgical correction.
Taxonomy of breast cancer based on normal cell phenotype predicts outcome
Authors: Sandro Santagata, Ankita Thakkar, Ayse Ergonul, Bin Wang, Terri Woo, Rong Hu, J. Chuck Harrell, George McNamara, Matthew Schwede, Aedin C. Culhane, David Kindelberger, Scott Rodig, Andrea Richardson, Stuart J. Schnitt, Rulla M. Tamimi, Tan A. Ince
Journal: Journal of Clinical Investigation (2014)

Accurate classification is essential for understanding the pathophysiology of a disease and can inform therapeutic choices. For hematopoietic malignancies, a classification scheme based on the phenotypic similarity between tumor cells and normal cells has been successfully used to define tumor subtypes; however, use of normal cell types as a reference by which to classify solid tumors has not been widely emulated, in part due to more limited understanding of epithelial cell differentiation compared with hematopoiesis. To provide a better definition of the subtypes of epithelial cells comprising the breast epithelium, we performed a systematic analysis of a large set of breast epithelial markers in more than 15,000 normal breast cells, which identified 11 differentiation states for normal luminal cells. We then applied information from this analysis to classify human breast tumors based on normal cell types into 4 major subtypes, HR0-HR3, which were differentiated by vitamin D, androgen, and estrogen hormone receptor (HR) expression. Examination of 3,157 human breast tumors revealed that these HR subtypes were distinct from the current classification scheme, which is based on estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. Patient outcomes were best when tumors expressed all 3 hormone receptors (subtype HR3) and worst when they expressed none of the receptors (subtype HR0). Together, these data provide an ontological classification scheme associated with patient survival differences and provides actionable insights for treating breast tumors.
Effects of mTOR Inhibitor Everolimus (RAD001) on Bladder Cancer Cells
Authors: Edmund Chiong, I-Ling Lee, Ali Dadbin, Anita L. Sabichi, Loleta Harris, Diana Urbauer, David J. McConkey, Rian J. Dickstein, Tiewei Cheng, H. Barton Grossman
Journal: Clinical Cancer Research (2011)

Abstract Purpose: We investigated the effect of the mTOR inhibitor RAD001 (everolimus) on human bladder cancer (BC) cells in vitro and in vivo. Experimental Design: The effect of RAD001 on the growth of UM-UC-3, UM-UC-6, UM-UC-9, and UM-UC-14 BC cells were assessed by crystal violet and [3H]thymidine incorporation assays. Flow cytometric cell-cycle analyses were done to measure the apoptotic cell fraction. Protein synthesis was measured using tritium-labeled leucine incorporation assays. The effects of RAD001 on the mTOR pathway were analyzed by Western blotting. To test the effects of RAD001 in vivo, UM-UC-3, UM-UC-6, and UM-UC-9 cells were subcutaneously implanted into nude mice. Tumor-bearing mice were treated orally with RAD001 or placebo. Tumors were harvested for immunohistochemical analysis. Results: In vitro, RAD001 transiently inhibited BC cell growth in a dose-dependent manner. This effect was augmented by re-treatment of cells after 3 days. UM-UC-14 cells were the most sensitive to RAD001, whereas UM-UC-9 cells were the least sensitive. After re-treatment with RAD001, only sensitive cell lines showed G1-phase arrest, with no evidence of apoptosis. RAD001 significantly inhibited the growth of tumors that were subcutaneously implanted in mice. Inhibition of protein synthesis through the S6K and 4EBP1 pathways seems to be the main mechanism for the RAD001-induced growth inhibition. However, inhibition of angiogenesis was the predominant mechanism of the effect of RAD001 on UM-UC-9 cells. Conclusions: The mTOR inhibitor RAD001 inhibits growth of BC cells in vitro. RAD001 is effective in treating BC tumors in an in vivo nude mouse model despite the heterogeneity of in vitro responses. Clin Cancer Res; 17(9); 2863–73. ©2011 AACR.
HOXA9 promotes homotypic and heterotypic cell interactions that facilitate ovarian cancer dissemination via its induction of P-cadherin
Authors: Song Ko, Honami Naora
Journal: Molecular Cancer (2014)

Epithelial ovarian cancer (EOC) is a lethal disease that frequently involves the peritoneal cavity. Dissemination of EOC is a multi-step process in which exfoliated tumor cells survive in the peritoneal fluid as multi-cellular aggregates and then form invasive implants on peritoneal surfaces. The mechanisms that control this process are poorly understood. We previously identified that high expression of the developmental patterning gene HOXA9 is associated with poor survival in EOC patients. In this study, we investigated the significance and mechanisms of HOXA9 in controlling aggregation and implantation of floating EOC cells.HOXA9 was inhibited by shRNAs or expressed in EOC cells that were propagated in suspension cultures and in the peritoneal cavity of mice. Cell death was assayed by flow cytometry and ELISA. Cell aggregation, attachment and migration were evaluated by microscopy, transwell chamber assays and histopathologic analysis. DNA-binding of HOXA9 and its effect on expression of the cell adhesion molecule P-cadherin were assayed by chromatin immunoprecipitation, quantitative RT-PCR and Western blot. HOXA9 and P-cadherin expression was evaluated in publicly available datasets of EOC clinical specimens.We identified that HOXA9 promotes aggregation and inhibits anoikis in floating EOC cells in vitro and in xenograft models. HOXA9 also stimulated the ability of EOC cells to attach to peritoneal cells and to migrate. HOXA9 bound the promoter of the CDH3 gene that encodes P-cadherin, induced CDH3 expression in EOC cells, and was associated with increased CDH3 expression in clinical specimens of EOC. Inhibiting P-cadherin in EOC cells that expressed HOXA9 abrogated the stimulatory effects of HOXA9 on cell aggregation, implantation and migration. Conversely, these stimulatory effects of HOXA9 were restored when P-cadherin was reconstituted in EOC cells in which HOXA9 was inhibited.These findings indicate that HOXA9 contributes to poor outcomes in EOC in part by promoting intraperitoneal dissemination via its induction of P-cadherin.
Chronic Liver Disease and Acetaminophen
Authors: G. KENNETH JOHNSON
Journal: Annals of Internal Medicine (1977)

A 59-year-old female patient with arthritis developed liver function abnormalities while taking therapeutic doses of acetaminophen. Liver biopsy showed evidence of acute and chronic liver damage. Rechallenge with acetaminophen induced abnormal liver functions almost immediately. The patient has been followed for 2 years since that challenge and remains asymptomatic. Biochemical tests of liver function have returned to normal.
Homeostatically proliferating CD4+ T cells are involved in the pathogenesis of an Omenn syndrome murine model
Authors: Khie Khiong, Masaaki Murakami, Chika Kitabayashi, Naoko Ueda, Shin-ichiro Sawa, Akemi Sakamoto, Brian L. Kotzin, Stephen J. Rozzo, Katsuhiko Ishihara, Marileila Verella-Garcia, John Kappler, Philippa Marrack, Toshio Hirano
Journal: Journal of Clinical Investigation (2007)

Patients with Omenn syndrome (OS) have hypomorphic RAG mutations and develop varying manifestations of severe combined immunodeficiency. It is not known which symptoms are caused directly by the RAG mutations and which depend on other polymorphic genes. Our current understanding of OS is limited by the lack of an animal model. In the present study, we identified a C57BL/10 mouse with a spontaneous mutation in, and reduced activity of, RAG1. Mice bred from this animal contained high numbers of memory-phenotype T cells and experienced hepatosplenomegaly and eosinophilia, had oligoclonal T cells, and demonstrated elevated levels of IgE, major symptoms of OS. Depletion of CD4+ T cells in the mice caused a reduction in their IgE levels. Hence these “memory mutant” mice are a model for human OS; many symptoms of their disease were direct results of the Rag hypomorphism and some were caused by malfunctions of their CD4+ T cells.
The opportunity cost model: Automaticity, individual differences, and self-control resources
Authors: Martin S. Hagger
Journal: Behavioral and Brain Sciences (2013)

Abstract I contend that Kurzban et al.'s model is silent on three issues. First, the extent to which opportunity-cost computations are automatic or deliberative is unclear. Second, the role of individual differences in biasing opportunity-cost computations needs elucidating. Third, in the absence of “next-best” tasks, task persistence will be indefinite, which seems unfeasible, so perhaps integration with a limited-resource account is necessary.
Arginine at positions 13 or 70-71 in pocket 4 of HLA-DRB1 alleles is associated with susceptibility to tuberculoid leprosy.
Authors: L Zerva, B Cizman, N K Mehra, S K Alahari, R Murali, C M Zmijewski, M Kamoun, D S Monos
Journal: The Journal of Experimental Medicine (1996)

Evaluation of human histocompatibility leukocyte antigen (HLA) class II genes in 54 cases of tuberculoid leprosy (TL) and 44 controls has shown a positive association with HLA-DRB1 alleles that contain Arg13 or Arg70-Arg71. Among TL patients, 87% carry specific alleles of DRB1 Arg13 or Arg70-Arg71 as compared to 43% among controls (p = 5 x 10(-6)) conferring a relative risk of 8.8. Thus, susceptibility to TL involves three critical amino acid positions of the beta chain, the side chains of which, when modeled on the DR1 crystal structure, line a pocket (pocket 4) accommodating the side chain of a bound peptide. This study suggests that disease susceptibility may be determined by the independent contribution of polymorphic residues participating in the formation of a functional arrangement (i.e., pocket) within the binding cleft of an HLA molecule.
A Us Study Of 5-grass Pollen Allergen Extract In Adults With Grass Pollen-induced Allergic Rhinoconjunctivitis - Results Of Secondary Efficacy Assessments
Authors: L. Cox, T.B. Casale, A. Nayak, P. Creticos, A. Montagut, R.K. Zeldin
Journal: Journal of Allergy and Clinical Immunology (2012)
Isolation and Partial Characterization of an Epiglycanin-Like Glycoprotein From a New Non-Strain-Specific Subline of TA3 Murine Mammary Adenocarcinoma&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: J F Codington, A G Cooper, D K Miller, H S Slayter, M C Brown, C Silber, R W Jeanloz
Journal: JNCI Journal of the National Cancer Institute (1979)

A new non-strain-specific ascites subline of the TA3 mammary adenocarcinoma TA3-MM, which arose in vivo from the strain-specific TA3-St subline during an acute respiratory illness of the syngeneic mouse strain A/HeHa hosts, possessed at its surface a glycoprotein not found on the parent TA3-St cell. This glycoprotein, termed TA3-MM epiglycanin, was characterized by a high molecular weight (500,000), by potent inhibition of hemagglutination by the Vicia gramines lectin, and by carbohydrate and amino acid compositions nearly identical to those of the glycoprotein epiglycanin present at the surface of the allotransplantable TA3-Ha ascites cell. By electron microscopic examination, TA3-MM epiglycanin appeared as long extended rods with widths (2.5 nm) and lengths (450--500 nm) similar to those of TA3-Ha epiglycanin. Incubation of each of two sublines of the TA3-MM ascites cell, TA3-MM/1 and TA3-MM/2, with a modified trypsin followed by column chromatography produced approximately 1.0- and 0.2-fold as much epiglycanin-like material, respectively, as was obtained from the TA3--a ascites cell. Continuous growth of the TA3-MM cell in suspension culture resulted in an almost complete disappearance of epiglycanin in a manner demonstrated earlier for the TA3-Ha cell grown under similar conditions. Allotransplantability in the TA3-MM cell may be due, at least in part, to masking a histocompatibility antigens by epiglycanin-like molecules.
Pavlov's Works
Authors: J. A. Ardis
Journal: BMJ (1957)

<b>Background:</b> Despite the high lifetime prevalence of depression in multiple sclerosis (MS), its longitudinal course is poorly understood. <b>Objective:</b> To examine the longitudinal course of and reliable change in different depression symptom clusters in MS, and the longitudinal association of interferon beta treatment and coping with depression symptoms. <b>Methods:</b> 53 MS patients were examined at two time points three years apart on the Beck Depression Inventory (BDI) and the Chicago Multiscale Depression Inventory (CMDI). <b>Results:</b> Correlations from time 1 to time 2 for BDI, CMDI-total, CMDI-evaluative scale, and CMDI-vegetative scale were all highly significant, and reliable change indices reflected little change over time. In contrast, the correlation over time for the CMDI-mood scale was significantly lower (p&lt;0.05) than the CMDI-evaluative and CMDI-vegetative scale correlations, and over 40% of patients showed reliable change. Patients who improved in their mood showed increased use of active coping, while patients who worsened showed <i>decreased</i> active coping strategies; the latter were also significantly more likely to have been taking interferon beta drugs at both time points than patients who did not change in their mood functioning. <b>Conclusions:</b> Mood symptoms of depression are significantly more variable over time than neurovegetative or negative evaluative symptoms in MS patients. Decreased use of active coping strategies may put patients at risk of increased depressed mood, whereas increased use of active coping may result in decreased depressed mood longitudinally. Interferon beta use may put patients at risk of increases in depressed mood.
Mortality and morbidity from respiratory diseases in childhood in The Netherlands, 1980-1987
Authors: J Wever-Hess, A M Wever, J L Yntema
Journal: European Respiratory Journal (1991)

National mortality and hospitalization data from the Netherlands were analysed for asthma (International Classification of Diseases) (ICD 493), acute bronchi(oli)tis (ICD 466), pneumonia and influenza (ICD 480-487), and other chronic obstructive pulmonary diseases (ICD 490 + 491 + 492 + 496) in children aged 0-14 yrs for 1980-1987. No trends were seen in the mortality in age groups 0-4 yrs and 5-14 yrs, which actually concerned small numbers. In general a tendency towards increasing hospital admission rates for respiratory diseases was observed in both sexes in age groups 0-4 yrs and 5-9 yrs but not in age group 10-14 yrs, and significant increases were found for asthma in males and females aged 0-4 yrs and in males aged 5-9 yrs, and for acute bronchitis in females aged 5-9 yrs. Hospital admission rates in the Netherlands for asthma appeared to be low compared to other countries. The average length of stay, however, for both asthma and the other respiratory diseases was substantial though declining. Clinical information is required on possible causal factors of the apparent need for hospitalization for reactive airway disorders in young children, and on the management of asthma in particular.
Epithelial Cells From Chronic Rhinosinusitis Patients Are Hyporesponsive To Bacteria: Evidence Of Innate Immune Dysfunction In CRS
Authors: C. Divoy, S. Rousseau, J. Berube, L. Mfuna Endam, A. Filali-Mouhim, J. Madrenas, Y. Berhiaume, M. Desrosiers
Journal: Journal of Allergy and Clinical Immunology (2011)
WIHTE SCALP HAIRS TURNING BLACK—AN UNUSUAL REVERSAL OF THK AGEIN PROCESS
Authors: STANLEY COMAISH
Journal: British Journal of Dermatology (1972)

Journal Article WIHTE SCALP HAIRS TURNING BLACK—AN UNUSUAL REVERSAL OF THK AGEIN PROCESS Get access STANLEY COMAISH STANLEY COMAISH Department of Dermatology, University of Newcastle upon Tyne Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 86, Issue 5, 1 May 1972, Pages 513–514, https://doi.org/10.1111/j.1365-2133.1972.tb16105.x Published: 01 May 1972 Article history Accepted: 10 November 1971 Published: 01 May 1972
End-of-life decision-making in respiratory intermediate care units: a European survey
Authors: S. Nava, C. Sturani, S. Hartl, G. Magni, M. Ciontu, A. Corrado, A. Simonds
Journal: European Respiratory Journal (2007)

A survey was performed on behalf of the European Respiratory Society to assess end-of-life practices in patients admitted to European respiratory intermediate care units and high dependency units over a 6-month period. A 33-item questionnaire was sent by e-mail to physicians throughout Europe and the response rate was 28 (29.5%) out of 95. A total of 6,008 patients were admitted and an end-of-life decision was taken in 1,292 (21.5%). The mortality rate in these patients was 68% (884 out of 1,292). The patients received similar proportions of withholding of treatment (298 (23%) out of 1292), do-not-resuscitate or do-not-intubate orders (442 (34%) out of 1,292) and noninvasive mechanical ventilation as the ceiling of ventilatory care (402 (31%) out of 1,292). Withdrawal of therapy was employed in 149 (11%) out of 1,292 patients and euthanasia in one. Do-not-intubate/do-not-resuscitate orders were more frequently used in North compared with South Europe. All of the 473 competent patients directly participated in the decision, whereas, in 722 (56%) out of 1,292 cases, decision-making was reported to be shared with the nurses. In European respiratory intermediate care units and high dependency units, an end-of-life decision is taken for 21.5% of patients admitted. Withholding of treatment, do-not-intubate/do-not-resuscitate orders and noninvasive mechanical ventilation as the ventilatory care ceiling are the most common procedures. Competent patients are often involved, together with nurses.