tbuckley/cabot-search huggingface dataset:
Cancer of the Gastrointestinal Tract Among Japanese and White Immigrants in Los Angeles County&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Hiroyuki Shimizu, Thomas M. Mack
 5, Ronald K. Ross, Brian E. Henderson
Journal: JNCI Journal of the National Cancer Institute (1987)

With the use of age-adjusted incidence rates and proportional incidence ratios, investigators studied the risk of cancer of the stomach and 3 subdivisions of the large bowel in three race-ethnic groups—Spanish surnamed whites, other whites, and Japanese—and compared Los Angeles County native residents, immigrants, and representative “homeland” populations. The risk pattern for each of the four anatomic sites was quite distinctive, suggesting at least four different etiologic complexes. For each site the observed gradients of risk are nearly identical for each sex, usually with risk for immigrants intermediary between that for homeland residents and that for local natives; the differences between race-ethnic groups are consistent with known international patterns. Particularly notable is the contrast between the low risks of cancer of both the sigmoid and the rectum in Japan and the high risks for Japanese immigrants to Los Angeles, which are nearly double those of their U.S. white neighbors. In all instances, and especially for both the upper and lower colon, the influence of the adult environment predominates over that of the early environment. The environmental determinants of stomach cancer do not always appear in inverse correlation with those of colon cancer, since Japanese immigrants to Los Angeles and their descendants are at high absolute and relative risk of both neoplasms. Our findings suggest that patterns of risk in relation to migration are complex and defy simple dietary or other interpretation. Without more information about the impact of migration to the United States on qualitative and quantitative aspects of lifestyle, it is not possible to put forward simple hypotheses that explain all available facts.
The Diversity and Molecular Evolution of B-Cell Receptors during Infection
Authors: Kenneth B. Hoehn, Anna Fowler, Gerton Lunter, Oliver G. Pybus
Journal: Molecular Biology and Evolution (2016)

B-cell receptors (BCRs) are membrane-bound immunoglobulins that recognize and bind foreign proteins (antigens). BCRs are formed through random somatic changes of germline DNA, creating a vast repertoire of unique sequences that enable individuals to recognize a diverse range of antigens. After encountering antigen for the first time, BCRs undergo a process of affinity maturation, whereby cycles of rapid somatic mutation and selection lead to improved antigen binding. This constitutes an accelerated evolutionary process that takes place over days or weeks. Next-generation sequencing of the gene regions that determine BCR binding has begun to reveal the diversity and dynamics of BCR repertoires in unprecedented detail. Although this new type of sequence data has the potential to revolutionize our understanding of infection dynamics, quantitative analysis is complicated by the unique biology and high diversity of BCR sequences. Models and concepts from molecular evolution and phylogenetics that have been applied successfully to rapidly evolving pathogen populations are increasingly being adopted to study BCR diversity and divergence within individuals. However, BCR dynamics may violate key assumptions of many standard evolutionary methods, as they do not descend from a single ancestor, and experience biased mutation. Here, we review the application of evolutionary models to BCR repertoires and discuss the issues we believe need be addressed for this interdisciplinary field to flourish.
Abstract 16943: Abnormal Immunomodulatory Function of Mesenchymal Stem Cells From Elderly Patients With Coronary Artery Disease: A Novel Pro-Atherogenic Mechanism?
Authors: Ozge Kizilay, Dominique Shum-Tim, Maximillien Lora, Jonathan Afilalo, Ines Colmegna
Journal: Circulation (2013)

BACKGROUND: Advancing age and its associated chronic low-grade inflammatory state known as “inflammaging” are risk factors for the development and progression of atherosclerosis and cardiovascular ...
Abstract 340: Heat Shock Proteins HSP90 and HSP70 Mediate Opioid- and GSK3β-induced Cardioprotection
Authors: Sarah K Jimenez, Bryce A Small, Anna K Hsu, Garrett J Gross, Eric R Gross
Journal: Circulation Research (2014)

Previously, opioids were established to reduce myocardial injury in an ischemic preconditioning (IPC)-like manner, involving a central and downstream role of glycogen synthase kinase-3 beta (GSK-3β) inhibition. However, the mechanism of GSK-3β inhibition mediating cardioprotection and the protein partners involved has not been fully elucidated. Hence, we used a non-biased sequence scan of the proteome to determine potential GSK-3β protein partners and tested whether two candidate proteins, heat shock proteins (HSP) 70 and 90, are involved in the mechanism of opioid-induced cardioprotection. A non-biased BLAST search was performed for putative GSK-3β target substrates, based upon the sequence motif S/T-X-X-X-S/T. Approximately 700 proteins were identified to have this moiety, including many of the HSP protein class, including HSP70 and HSP90. To determine whether HSP70 or HSP90 are indeed important in opioid-induced cardioprotection, rats were subjected to an in vivo myocardial ischemia-reperfusion protocol consisting of 30 minutes of ischemia and 2 hours of reperfusion of the left anterior descending coronary artery followed by infarct size assessment. Either morphine (0.3mg/kg) or inhibition of GSK-3β using SB216763 (0.6mg/kg), reduced infarct size compared to control (42.21±1*% and 41.09±2*%, respectively versus control 60.38±1.2, *P&lt;0.01). Inhibition of HSP70 using desoxysperguanalin (DSG), or HSP90 using radicicol (RAD), abrogated morphine-induced protection (56.09±2 and 58.64±1, respectively). Either DSG or RAD partially inhibited protection in the presence of GSK-3β (47.28±1.071 and 49.88±3.09). Our results suggest that morphine-induced cardioprotection occurs by a HSP70 and HSP90- dependent mechanism, with this HSP machinery partially required for GSK3β-inhibition-induced cardioprotection. Further understanding of this mechanism is important, considering many agents targeting HSP are currently in development as novel cancer treatments, which may have detrimental effects on the myocardial salvage mediated by opioids or by GSK3β-inhibition.
Cooperative activity of α4β1 and α4β7 integrins in mediating human B-cell lymphoma adhesion and chemotaxis on fibronectin through recognition of multiple synergizing binding sites within the central cell-binding domain
Authors: Zhinan Yin, Emiliana Giacomello, Elena Gabriele, Luciano Zardi, Shin ichi Aota, Kenneth M. Yamada, Barbara Skerlavaji, Roberto Doliana, Alfonso Colombatti, Roberto Perris
Journal: Blood (1999)
P-338 Non-Operative Treatment after Neo-Adjuvant Short Course Radiotherapy (The Tlalpan Regime) in a combined modality for Locally Advanced Rectal Cancer with risk factors at the Instituto Nacional de Cancerología (México)
Authors: J. Zamora Moreno, G. Santiago Concha, E. Mitsoura, E. Ruiz Garcia, V. Aiello Crocifoglio
Journal: Annals of Oncology (2015)
4'Epidoxorubicin (epirubicin): activity in hepatocellular carcinoma.
Authors: H S Hochster, M D Green, J Speyer, E Fazzini, R Blum, F M Muggia
Journal: Journal of Clinical Oncology (1985)

Doxorubicin provides the most consistent response rate in hepatocellular carcinoma. We therefore initiated a trial with its analog 4'epidoxorubicin. Eighteen patients, all without prior treatment, were given the drug as a single agent every 3 weeks with dose escalation whenever possible. Five patients were treated by six-hour infusion and 13 by intravenous (IV) bolus injection, with the median dose being 90 mg/m2. The patients were of diverse ethnic background and included some with underlying cirrhosis and hepatitis B surface antigenemia. Three patients had partial remissions (6, 12, 48 weeks) for a response rate of 17%. Four patients also had prolonged stable disease (14, 26, 27, 38 weeks). Toxicity was mild, although cardiac toxicity developed in three patients at 685, 825, and 1,460 mg/m2 cumulative dose. The response to 4'epidoxorubicin in this study appears to be equivalent to the reported response rates for doxorubicin, with decreased toxicity.
Reactions Obtained With Transferred Lymphocytes in Patients With Advanced Cancer&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: B. G. Hattler, Jr., M.D., D. B. Amos, M.D.
Journal: JNCI Journal of the National Cancer Institute (1965)

Lymphocytes were inoculated intradermally into 31 patients with far-advanced cancer and into 10 with less-advanced disease. In 23 instances each patient served in turn as donor and recipient for lymphocytes from other participants in the experiment. As a control, patients also received lymphocytes from a normal donor. The degree of reactivity measured as erythema and induration at 48 hours was related to the clinical condition of the recipients. Cells from other cancer patients or a normal subject provoked minimum induration in advanced cancer subjects. A nearly normal reaction was seen when cells from cancer patients were transferred to 2 normal subjects. It is suggested that the reactions were predominantly of the host-versus-graft type. Eighteen cancer patients showing a depressed reactivity to a battery of microbial antigens were used in separate experiments to determine their ability to accept “adoptive transfer” of delayed hypersensitivity during the anergic state. In all instances transfer of donor reactivity with lymphocytes was successful. Reactions sometimes remained positive for several weeks. The patients' ability to support adoptive immunity suggests that the defect is due, at least in part, to the lymphocytes of the cancer subject rather than the result of inhibitors or nutritional or metabolic deficiencies.
Biologic Properties of Viable Deletion Mutants of Simian Virus 40 (SV40) Rescued From the Cells of an SV40-lnduced Hamster Lymphocytic Leukemia&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: George Th. Diamandopoulos, MD., Gordon Carmichael, Ph.D.
Journal: JNCI Journal of the National Cancer Institute (1983)

A lymphocytic leukemia induced by the oncogenic DNA simian virus 40 (SV40) in an inbred LSH/SsLak Syrian golden hamster was evoked to produce infectious SV40 by fusion of the leukemia cells with grivet monkey kidney (GMK) cells and by exposure of the leukemia cells to the chemical inducers mitomycin C and cycloheximide. Plaque-purified viable substrains of the rescued SV40 when studied by restriction endonuclease digestion of viral DNA were found to contain small deletions within the Hind III restriction fragment C. These deletions lay near the viral origin of DNA replication. Ten plaque-purified substrains of the rescued virus identified by immunofluorescence as being SV40 were found, when compared to the wild-type SV40, to replicate slowly and to form small plaques. Although these substrains transformed NIH/3T3 cells as efficiently as the wild-type SV40 in tissue culture, they were generally less oncogenic in vivo—7 of the 10 failed to induce tumors. The 3 oncogenic SV40-rescued substrains were not found to exhibit “lymphocytotropism,” i.e., the capacity to infect and neoplastically transform preferentially hamster lymphocytes. Thus the hamster lymphocytic leukemia originally induced by the wild-type SV40 was most likely a chance-stochastic event rather than the result of tropism-determinism mediated by the virus, as is usually the case with leukemogenic RNA viruses.
OSTEOPOROSIS IS PREVALENT AND EXERCISE CAPACITY INDEPENDENTLY PREDICTS BONE MINERAL DENSITY IN MALE PATIENTS WITH ACUTE DECOMPENSATED HEART FAILURE
Authors: Jong-Chan Youn, Yumie Rhee, Jaewon Oh, Namki Hong, Sungha Park, Sang-Hak Lee, Donghoon Choi, Seok-Min Kang
Journal: Journal of the American College of Cardiology (2014)
Medical Assistant–Based Care Management for High-Risk Patients in Small Primary Care Practices
Authors: Tobias Freund, Frank Peters-Klimm, Cynthia M. Boyd, Cornelia Mahler, Jochen Gensichen, Antje Erler, Martin Beyer, Matthias Gondan, Justine Rochon, Ferdinand M. Gerlach, Joachim Szecsenyi
Journal: Annals of Internal Medicine (2016)

Background: Patients with multiple chronic conditions are at high risk for potentially avoidable hospitalizations, which may be reduced by care coordination and self-management support. Medical assistants are an increasingly available resource for patient care in primary care practices. Objective: To determine whether protocol-based care management delivered by medical assistants improves care in patients at high risk for future hospitalization in primary care. Design: Two-year cluster randomized clinical trial. (Current Controlled Trials: ISRCTN56104508) Setting: 115 primary care practices in Germany. Patients: 2076 patients with type 2 diabetes, chronic obstructive pulmonary disease, or chronic heart failure and a likelihood of hospitalization in the upper quartile of the population, as predicted by an analysis of insurance data. Intervention: Protocol-based care management, including structured assessment, action planning, and monitoring delivered by medical assistants, compared with usual care. Measurements: All-cause hospitalizations at 12 months (primary outcome) and quality-of-life scores (12-Item Short Form Health Survey [SF-12] and EuroQol instrument [EQ-5D]). Results: Included patients had an average of 4 co-occurring chronic conditions. All-cause hospitalizations did not differ between groups at 12 months (risk ratio [RR], 1.01 [95% CI, 0.87 to 1.18]) and 24 months (RR, 0.98 [CI, 0.85 to 1.12]). Quality of life (differences, 1.16 [CI, 0.24 to 2.08] on SF-12 physical component and 1.68 [CI, 0.60 to 2.77] on SF-12 mental component) and general health (difference on EQ-5D, 0.03 [CI, 0.00 to 0.05]) improved significantly at 24 months. Intervention costs totaled $10 per patient per month. Limitation: Small number of primary care practices and low intensity of intervention. Conclusion: This low-intensity intervention did not reduce all-cause hospitalizations but showed positive effects on quality of life at reasonable costs in high-risk multimorbid patients. Primary Funding Source: AOK Baden-Württemberg and AOK Bundesverband.
Abstract 19046: RBC-Macrophage Inflammatory Axis: Potential Role in Atherosclerosis
Authors: Ramprasad Srinivasan, Danielle Coyle, Neil Batra, Victor Blanco, Wilson Tong, Mary Palascak, Robert S Franco, Tapan Chatterjee, David Y Hui, W. Sean Davidson, Bruce J Aronow, Evgeny Ozhegov, David Manka, Abigail Peairs, Andra Blomkalns, Neal L Weintraub, Vladimir Y Bogdanov
Journal: Circulation (2012)

Background: Red blood cells (RBC) modulate vasoreactivity, serve as a reservoir for chemokines via binding to Duffy antigen receptor for chemokines (DARC), and contribute to the pathology of atherosclerotic plaque rupture, suggesting a broad role in vascular pathophysiology. High fat diet (HFD) is known to negatively impact vascular function and modify RBC membrane composition, but how this affects RBC chemokine binding, and interaction with macrophages and blood vessels, is unknown. Methods and Results: RBC from C57BL/6J mice fed chow diet (chow RBC) or 60% HFD (HFD RBC) for 16 weeks were collected and studied in vitro and in vivo. Reactive oxygen species (DCFH fluorescence) and phosphatidylserine externalization (annexin V binding), a potential signal for RBC phagocytosis, were increased ~1.5 fold (p&lt;0.05) in HFD RBC compared to chow RBC. HFD RBC released ~1.5 fold more monocyte chemoattractant protein-1 (MCP-1) (p&lt;0.05) compared to chow RBC upon addition of heparin to disrupt DARC binding. In a transwell system, HFD RBC, as compared with chow RBC, produced a significant increase in the migration of thioglycollate-elicited macrophages through an endothelial monolayer (p&lt;0.05). Incubation of HFD RBC with murine macrophages demonstrated a ~1.5 fold (p&lt;0.05) increase in phagocytosis compared to chow RBC; upon their internalization by macrophages, HFD RBC more potently upregulated transcription of major pro-inflammatory chemokines Il-1b, Ccl3, and Cxcl2. As compared with chow RBC, exposure of murine aortic segments to HFD RBC under orbital shear conditions led to enhanced endothelial activation as evidenced by increased adhesion of labeled murine macrophages to the aortic endothelium (p&lt;0.05). Finally, when labeled and injected in vivo, HFD RBC exhibited a ~3 fold (p&lt;0.05) increase in splenic phagocytosis as compared with chow RBC. Conclusion: HFD profoundly impact RBC biology, inducing oxidative stress, altering membrane phospholipid display, and increasing chemokine release, phagocytosis by macrophages, and macrophage-blood vessel interactions. These novel findings suggest that RBC may play an important role in transducing vascular inflammation, and thus contributing to atherosclerosis, during HFD.
Therapeutic targeting of oxygen-sensing prolyl hydroxylases abrogates ATF4-dependent neuronal death and improves outcomes after brain hemorrhage in several rodent models
Authors: Saravanan S. Karuppagounder, Ishraq Alim, Soah J. Khim, Megan W. Bourassa, Sama F. Sleiman, Roseleen John, Cyrille C. Thinnes, Tzu-Lan Yeh, Marina Demetriades, Sandra Neitemeier, Dana Cruz, Irina Gazaryan, David W. Killilea, Lewis Morgenstern, Guohua Xi, Richard F. Keep, Timothy Schallert, Ryan V. Tappero, Jian Zhong, Sunghee Cho, Frederick R. Maxfield, Theodore R. Holman, Carsten Culmsee, Guo-Hua Fong, Yijing Su, Guo-li Ming, Hongjun Song, John W. Cave, Christopher J. Schofield, Frederick Colbourne, Giovanni Coppola, Rajiv R. Ratan
Journal: Science Translational Medicine (2016)

Blocking oxygen-sensing prolyl hydroxylases in the rodent CNS enhances functional recovery after brain hemorrhage.
Abstract P056: RalGDS-Dependent Cardiomyocyte Autophagy in Load-Induced Ventricular Hypertrophy
Authors: Oktay F Rifki, Brian O Bodemann, Michael A White, Joseph A Hill
Journal: Circulation Research (2011)

Background: Recent work has demonstrated that autophagy, a phylogenetically conserved, lysosome-mediated pathway of protein degradation, is a key participant in pathological cardiac remodeling. One common feature of cell growth and autophagy is membrane biogenesis and processing. The exocyst, an octomeric protein complex involved in vesicle trafficking, is implicated in numerous cellular processes, yet its role in cardiomyocyte plasticity is unknown. Here, we set out to explore the role of small G protein-dependent membrane trafficking in stress-induced cardiomyocyte remodeling and autophagy. Methods and Results: Hearts from mice lacking RalGDS ( Ralgds -/- ), a guanine exchange factor (GEF) for the Ral family of small GTPases, were similar to wild-type (WT) littermates in terms of ventricular structure, contractile performance, and gene expression. However, Ralgds -/- hearts manifested a blunted growth response (p&lt;0.05) to TAC-mediated pressure-overload stress as determined by heart weight to body weight ratios (HW/BW; WT, sham: 5.00 ± 0.21 mg/g, n=9; TAC: 6.93 ± 0.29, n=13; Ralgds -/- sham: 4.87 ± 0.19, n=6, TAC: 5.86 ± 0.10, n=6). Ventricular chamber size and contractile performance were unchanged in response to TAC in both genotypes. Interestingly, TAC-induced activation of the fetal gene program was similar in both genotypes despite the relative lack of hypertrophic growth in mutant hearts. Ralgds -/- mice also exhibited diminished load-induced cardiomyocyte autophagy. Consistent with the TAC findings, Ralgds -/- mice manifested a blunted autophagic response to 24-hour fasting, suggesting a generalized defect in autophagy. To explore underlying mechanisms, we tested in cultured neonatal cardiomyocytes two isoforms of Ral that are downstream of RalGDS (RalA, RalB) and whose actions are mediated by the exocyst. In these experiments, mTOR inhibition was maintained in response to starvation and rapamycin despite RalA or RalB knockdown; however, autophagy was diminished only in NRCM's with RalB knockdown, implicating RalB as required for cardiomyocyte autophagy. Conclusions: Together, these data implicate RalGDS-mediated induction of autophagy as a critical feature of load-induced cardiac hypertrophy.
Preventing Food Allergy in Infancy — Early Consumption or Avoidance?
Authors: Gary W.K. Wong
Journal: New England Journal of Medicine (2016)

Food allergy among children is common, affecting up to 8% of children younger than 3 years of age.1 It can be serious, even fatal, with hospital-discharge data from the United States documenting an increasing trend of food-induced anaphylaxis.2 In order to minimize accidental exposure to foods to which a child could be allergic, many schools in the United States have a "no sharing" policy for food.3 For decades, we had been trying to stem the rising tide of food allergy by urging parents to avoid exposing their children to foods such as egg, peanut, and fish early in life — . . .
Phase II study of the combination of the novel bioreductive agent, tirapazamine, with cisplatin in patients with advanced non-small-cell lung cancer
Authors: V.A. Miller, K.K. Ng, S.C. Grant, H. Kindler, B. Pizzo, R.T. Heelan, R. von Roemeling, M.G. Kris
Journal: Annals of Oncology (1997)

Purpose: Tirapazamine is a bioreductive compound synergistic with cisplatin in preclinical testing.This phase II study was conducted to evaluate the efficacy and toxicity of tirapazamine with cisplatin in patients with advanced non-small-cell lung cancer.Patients and methods: Twenty patients with unresectable stage III-B and IV non-small-cell lung cancer who had not received prior chemotherapy were given tirapazamine (390 mg/m 2 ) intravenously (i.v.) over two hours followed one hour later by cisplatin (75 mg/m 2 ) i.v. over one hour every 21 days.Results: Five of 20 patients (25%) had major objective responses (95% confidence interval, ll%-50%).Median dura-tion of response was eight months with a one-year survival of 40%.Toxicities included temporary hearing loss (25%), muscle cramping, diarrhea, skin rash and nausea/vomiting.No grade 3 or 4 hematologic or renal toxicity was observed.Conclusions: The combination of tirapazamine plus cisplatin appears to be safe and active in the treatment of advanced non-small lung cancer without a substantial increase in toxicity compared to cisplatin alone.A phase III randomized study comparing the combination to cisplatin alone has completed accrual.Further evaluation of tirapazamine with other active agents and in multi-modality therapy is warranted.