tbuckley/cabot-search huggingface dataset:
Biochemical Modulation of 5-Bromo-2'-deoxyuridine and 5-Iodo-2'-deoxyuridine Incorporation Into DNA in VX2 Tumor-Bearing Rabbits
Authors: P. L. Stetson, D. P. Normolle, J. A. Knol, N. J. Johnson, Z. Yang, E. Sakmar, D. Prieskorn, P. Terrio, C. A. Knutsen, W. D. Ensminger
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Biochemical Modulation of 5-Bromo-2'-deoxyuridine and 5-Iodo-2'-deoxyuridine Incorporation Into DNA in VX2 Tumor-Bearing Rabbits Get access Philip L. Stetson, Philip L. Stetson * 1Upjohn Center for Clinical Pharmacology and Department of PharmacologyUniversity of Michigan School of Medicine, Ann Arbor. * Correspondence to: Philip L. Stetson, M.D., Ph.D., Upjohn Center for Clinical Pharmacology, University of Michigan School of Medicine, 3700 Upjohn Center, Ann Arbor, MI 48109. Search for other works by this author on: Oxford Academic PubMed Google Scholar Daniel P. Normolle, Daniel P. Normolle 2Department of BiostatisticsUniversity of Michigan School of Medicine, Ann Arbor. Search for other works by this author on: Oxford Academic PubMed Google Scholar James A. Knol, James A. Knol 3Department of SurgeryUniversity of Michigan School of Medicine, Ann Arbor. Search for other works by this author on: Oxford Academic PubMed Google Scholar Norma J. Johnson, Norma J. Johnson 4Upjohn Center for Clinical PharmacologyUniversity of Michigan School of Medicine, Ann Arbor. Search for other works by this author on: Oxford Academic PubMed Google Scholar Zhaomin Yang, Zhaomin Yang 4Upjohn Center for Clinical PharmacologyUniversity of Michigan School of Medicine, Ann Arbor. Search for other works by this author on: Oxford Academic PubMed Google Scholar Ermelinda Sakmar, Ermelinda Sakmar 4Upjohn Center for Clinical PharmacologyUniversity of Michigan School of Medicine, Ann Arbor. Search for other works by this author on: Oxford Academic PubMed Google Scholar Diane Prieskorn, Diane Prieskorn 4Upjohn Center for Clinical PharmacologyUniversity of Michigan School of Medicine, Ann Arbor. Search for other works by this author on: Oxford Academic PubMed Google Scholar Patricia Terrio, Patricia Terrio 4Upjohn Center for Clinical PharmacologyUniversity of Michigan School of Medicine, Ann Arbor. Search for other works by this author on: Oxford Academic PubMed Google Scholar Conrad A. Knutsen, Conrad A. Knutsen 4Upjohn Center for Clinical PharmacologyUniversity of Michigan School of Medicine, Ann Arbor. Search for other works by this author on: Oxford Academic PubMed Google Scholar William D. Ensminger William D. Ensminger 5Upjohn Center for Clinical Pharmacology, Department of Pharmacology, and Department of Internal MedicineUniversity of Michigan School of Medicine, Ann Arbor. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 22, 20 November 1991, Pages 1659–1667, https://doi.org/10.1093/jnci/83.22.1659 Published: 20 November 1991 Article history Received: 20 May 1991 Revision received: 07 August 1991 Accepted: 16 August 1991 Published: 20 November 1991
Distinct Role of Antigen-Specific T Helper Type 1 (Th1) and Th2 Cells in Tumor Eradication in Vivo
Authors: Takashi Nishimura, Kenji Iwakabe, Masashi Sekimoto, Yasushi Ohmi, Takashi Yahata, Minoru Nakui, Takehito Sato, Sonoko Habu, Hiroyuki Tashiro, Marimo Sato, Akio Ohta
Journal: The Journal of Experimental Medicine (1999)

The role of T helper type 1 (Th1) and Th2 cells in tumor immunity was investigated using Th cells induced from ovalbumin (OVA)-specific T cell receptor transgenic mice. Although Th1 cells exhibited stronger cytotoxicity than Th2 cells, both cell types completely eradicated tumors when transferred into mice bearing A20 tumor cells transfected with the OVA gene (A20-OVA). Th1 cells eradicated the tumor mass by inducing cellular immunity, whereas Th2 cells destroyed the tumor by inducing tumor necrosis. Both Th1 and Th2 cells required CD8+ T cells to eliminate tumors, and neither of these cells were able to completely eliminate A20-OVA tumors from T and B cell–deficient RAG2−/− mice. Mice cured from tumors by Th1 and Th2 cell therapy rejected A20-OVA upon rechallenge, but CD8+ cytotoxic T lymphocytes were induced only from spleen cells prepared from cured mice by Th1 cell therapy. Moreover, we demonstrated that Th1 and Th2 cells used distinct adhesion mechanisms during tumor eradication: the leukocyte function-associated antigen (LFA)-1–dependent cell–cell adhesion step was essential for Th1 cell therapy, but not for Th2 cell therapy. These findings demonstrated for the first time the distinct role of antigen-specific Th1 and Th2 cells during eradication of established tumors in vivo.
The Ca2+-Dependent Release of the Mia40-Induced MICU1-MICU2 Dimer from MCU Regulates Mitochondrial Ca2+ Uptake
Authors: Carmelina Petrungaro, Katharina M. Zimmermann, Victoria Küttner, Manuel Fischer, Jörn Dengjel, Ivan Bogeski, Jan Riemer
Journal: Cell Metabolism (2015)
Management of Localized Kidney Cancer: Calculating Cancer-specific Mortality and Competing Risks of Death for Surgery and Nonsurgical Management
Authors: Maxine Sun, Andreas Becker, Zhe Tian, Florian Roghmann, Firas Abdollah, Alexandre Larouche, Pierre I. Karakiewicz, Quoc-Dien Trinh
Journal: European Urology (2013)
Problems in Psychotherapy With Suicidal Patients
Authors: Herbert Hendin, Ann Pollinger Haas, John T. Maltsberger, Bethany Koestner, Katalin Szanto
Journal: American Journal of Psychiatry (2006)

OBJECTIVE: The authors studied recurrent problems in psychotherapy with suicidal patients by examining the cases of patients who died by suicide while receiving open-ended psychotherapy and medication. METHOD: Therapists for 36 patients who died by suicide while in treatment filled out clinical, medication, and psychological questionnaires and wrote detailed case narratives. They then presented their cases at an all-day workshop, and critical problems were identified in the cases. RESULTS: Six recurrent problem areas were identified: poor communication with another therapist involved in the case, permitting patients or relatives to control the therapy, avoidance of issues related to sexuality, ineffective or coercive actions resulting from the therapist's anxieties about a patient's potential suicide, not recognizing the meaning of the patient's communications, and untreated or undertreated symptoms. CONCLUSIONS: These cases illuminate common problems therapists face in working with suicidal patients and highlight an unmet need for education of psychiatrists and other mental health professionals who work with this population.
“July Effect”: Impact of the Academic Year-End Changeover on Patient Outcomes
Authors: John Q. Young, Sumant R. Ranji, Robert M. Wachter, Connie M. Lee, Brian Niehaus, Andrew D. Auerbach
Journal: Annals of Internal Medicine (2011)

It is commonly believed that the quality of health care decreases during trainee changeovers at the end of the academic year.To systematically review studies describing the effects of trainee changeover on patient outcomes.Electronic literature search of PubMed, Educational Research Information Center (ERIC), EMBASE, and the Cochrane Library for English-language studies published between 1989 and July 2010.Title and abstract review followed by full-text review to identify studies that assessed the effect of the changeover on patient outcomes and that used a control group or period as a comparator.Using a standardized form, 2 authors independently abstracted data on outcomes, study setting and design, and statistical methods. Differences between reviewers were reconciled by consensus. Studies were then categorized according to methodological quality, sample size, and outcomes reported.Of the 39 included studies, 27 (69%) reported mortality, 19 (49%) reported efficiency (length of stay, duration of procedure, hospital charges), 23 (59%) reported morbidity, and 6 (15%) reported medical error outcomes; all studies focused on inpatient settings. Most studies were conducted in the United States. Thirteen (33%) were of higher quality. Studies with higher-quality designs and larger sample sizes more often showed increased mortality and decreased efficiency at time of changeover. Studies examining morbidity and medical error outcomes were of lower quality and produced inconsistent results.The review was limited to English-language reports. No study focused on the effect of changeovers in ambulatory care settings. The definition of changeover, resident role in patient care, and supervision structure varied considerably among studies. Most studies did not control for time trends or level of supervision or use methods appropriate for hierarchical data.Mortality increases and efficiency decreases in hospitals because of year-end changeovers, although heterogeneity in the existing literature does not permit firm conclusions about the degree of risk posed, how changeover affects morbidity and rates of medical errors, or whether particular models are more or less problematic.National Heart, Lung, and Blood Institute.
Subclinical Hypothyroidism Is an Independent Risk Factor for Atherosclerosis and Myocardial Infarction in Elderly Women: The Rotterdam Study
Authors: A. Elisabeth Hak, Huibert A.P. Pols, Theo J. Visser, Hemmo A. Drexhage, Albert Hofman, Jacqueline C.M. Witteman
Journal: Annals of Internal Medicine (2000)

Background: Overt hypothyroidism has been found to be associated with cardiovascular disease. Whether subclinical hypothyroidism and thyroid autoimmunity are also risk factors for cardiovascular disease is controversial. Objective: To investigate whether subclinical hypothyroidism and thyroid autoimmunity are associated with aortic atherosclerosis and myocardial infarction in postmenopausal women. Design: Population-based cross-sectional study. Setting: A district of Rotterdam, the Netherlands. Participants: Random sample of 1149 women (mean age ± SD, 69.0 ± 7.5 years) participating in the Rotterdam Study. Measurements: Data on thyroid status, aortic atherosclerosis, and history of myocardial infarction were obtained at baseline. Subclinical hypothyroidism was defined as an elevated thyroid-stimulating hormone level (>4.0 mU/L) and a normal serum free thyroxine level (11 to 25 pmol/L [0.9 to 1.9 ng/dL]). In tests for antibodies to thyroid peroxidase, a serum level greater than 10 IU/mL was considered a positive result. Results: Subclinical hypothyroidism was present in 10.8% of participants and was associated with a greater age-adjusted prevalence of aortic atherosclerosis (odds ratio, 1.7 [95% CI, 1.1 to 2.6]) and myocardial infarction (odds ratio, 2.3 [CI, 1.3 to 4.0]). Additional adjustment for body mass index, total and high-density lipoprotein cholesterol level, blood pressure, and smoking status, as well as exclusion of women who took β-blockers, did not affect these estimates. Associations were slightly stronger in women who had subclinical hypothyroidism and antibodies to thyroid peroxidase (odds ratio for aortic atherosclerosis, 1.9 [CI, 1.1 to 3.6]; odds ratio for myocardial infarction, 3.1 [CI, 1.5 to 6.3]). No association was found between thyroid autoimmunity itself and cardiovascular disease. The population attributable risk percentage for subclinical hypothyroidism associated with myocardial infarction was within the range of that for known major risk factors for cardiovascular disease. Conclusion: Subclinical hypothyroidism is a strong indicator of risk for atherosclerosis and myocardial infarction in elderly women.
Variability of contractile reserve in hibernating myocardium: dependence on the method of inotropic stimulation
Authors: B Malm
Journal: Cardiovascular Research (2002)

Objective: Contractile reserve during graded β-adrenergic stimulation identifies viability in patients with left ventricular dysfunction. Nevertheless, contractile reserve is frequently absent in viable, chronically dysfunctional myocardium with reduced resting flow (hibernating myocardium). The goal of this study was to evaluate the mechanisms responsible for limited contractile reserve in hibernating myocardium. Methods: Pigs were chronically instrumented with a left anterior descending coronary artery (LAD) stenosis to produce hibernating myocardium; and regional flow, function and hemodynamics were assessed during graded β-adrenergic stimulation (epinephrine). Results: The chronic LAD stenosis produced a critical reduction in coronary flow reserve with regional reductions in resting subendocardial flow (0.69±0.05 vs. 1.03±0.11 ml/min/g in shams, P<0.05) and wall thickening (2.0±0.4 vs. 4.3±0.4 mm in shams, P<0.05), consistent with hibernating myocardium. In sham controls, LAD flow and function increased during graded, steady-state increases in epinephrine. Nevertheless, despite similar external determinants of demand in animals with hibernating myocardium, neither subendocardial flow (peak response: 0.66±0.14 and peak dose: 0.58±0.13 ml/min/g, respectively) nor wall thickening (3.0±0.5 and 2.5±0.6 mm, respectively) increased during graded epinephrine infusion. However, during a transient epinephrine infusion to the maximum dose used in the graded protocol, flow remained unchanged (0.80±0.06 to 0.85±0.08 ml/min/g) but wall thickening improved (2.3±0.4 to 4.1±0.6 mm, P<0.05). Conclusions: These data indicate that variability in contractile reserve in hibernating myocardium is at least partly related to the protocol used for β-adrenergic stimulation. The blunted steady-state responses to β-adrenergic stimulation raise the possibility that, like moderate supply-induced ischemia, an exquisite matching between flow and function develops during moderate demand-induced ischemia. This prevents metabolic deterioration in hibernating myocardium but limits contractile function during increases in the external determinants of myocardial metabolism.
Molecular Imaging of Drug-Modulated Protein-Protein Interactions in Living Subjects
Authors: Ramasamy Paulmurugan, Tarik F. Massoud, Jing Huang, Sanjiv S. Gambhir
Journal: Cancer Research (2004)

Abstract Networks of protein interactions mediate cellular responses to environmental stimuli and direct the execution of many different cellular functional pathways. Small molecules synthesized within cells or recruited from the external environment mediate many protein interactions. The study of small molecule-mediated interactions of proteins is important to understand abnormal signal transduction pathways in cancer and in drug development and validation. In this study, we used split synthetic renilla luciferase (hRLUC) protein fragment-assisted complementation to evaluate heterodimerization of the human proteins FRB and FKBP12 mediated by the small molecule rapamycin. The concentration of rapamycin required for efficient dimerization and that of its competitive binder ascomycin required for dimerization inhibition were studied in cell lines. The system was dually modulated in cell culture at the transcription level, by controlling nuclear factor κB promoter/enhancer elements using tumor necrosis factor α, and at the interaction level, by controlling the concentration of the dimerizer rapamycin. The rapamycin-mediated dimerization of FRB and FKBP12 also was studied in living mice by locating, quantifying, and timing the hRLUC complementation-based bioluminescence imaging signal using a cooled charged coupled device camera. This split reporter system can be used to efficiently screen small molecule drugs that modulate protein-protein interactions and also to assess drugs in living animals. Both are essential steps in the preclinical evaluation of candidate pharmaceutical agents targeting protein-protein interactions, including signaling pathways in cancer cells.
Cardiac functional improvement in rats with myocardial infarction by up-regulating cardiac myosin light chain kinase with neuregulin
Authors: Xinghua Gu, Xifu Liu, Danling Xu, Xinyan Li, Ming Yan, Ying Qi, Weihai Yan, Wenqing Wang, Jing Pan, Yabei Xu, Bing Xi, Leilei Cheng, Jianguo Jia, Keqiang Wang, Junbo Ge, Mingdong Zhou
Journal: Cardiovascular Research (2010)

AimsRecombinant human neuregulin-1 (rhNRG-1) improves cardiac function in experimental heart failure models, but the underlying mechanism remains largely unknown. In this study, we evaluated whether rhNRG-1 could improve cardiac function via the cardiac myosin light chain kinase/myosin light chain 2 ventricular (cMLCK/MLC-2v) pathway in rats with myocardial infarction (MI).
150-kD oxygen-regulated protein is expressed in human atherosclerotic plaques and allows mononuclear phagocytes to withstand cellular stress on exposure to hypoxia and modified low density lipoprotein.
Authors: Y Tsukamoto, K Kuwabara, S Hirota, J Ikeda, D Stern, H Yanagi, M Matsumoto, S Ogawa, Y Kitamura
Journal: Journal of Clinical Investigation (1996)

The 150-kD oxygen-regulated protein (ORP150) was initially characterized based on its selective expression in astrocytes subjected to oxygen deprivation (Kuwabara, K., M. Matsumoto, J. Ikeda, O. Hori, S. Ogawa, Y. Maeda, K. Kitagawa, N. Imuta, K. Kinoshita, D.M. Stern, et al. 1996. J. Biol. Chem. 279:5025-5032). We have found that exposure of cultured human aortic smooth muscle cells and mononuclear phagocytes (MPs) to hypoxia (pO2 approximately 12-14 torr) induces ORP150 transcripts and production of the antigen, whereas incubation with either hydrogen peroxide, sodium arsenite, heat shock, or 2-deoxyglucose was without effect. Tissue extracts prepared from human atherosclerotic lesions demonstrated expression of ORP150 mRNA and antigen, vs lack of ORP150 in samples from nonatherosclerotic areas. In situ hybridization using ORP150 riboprobes showed the mRNA to be predominantly [correction of predominately] present in macrophages in in atherosclerotic plaques. Furthermore, autoantibody to ORP150 was demonstrated in the serum of patients with severe atherosclerosis, consistent with inducible in vivo expression of ORP150. Introduction of antisense oligonucleotide for ORP150 selectively diminished hypoxia-mediated induction of ORP150 antigen and reduced the viability of hypoxic MPs, especially in the presence of modified (oxidized/acetylated) LDL. In support of a role for ORP150 in the MPs' response to the microenvironment of an atheroma, the presence of oxidized LDL enhanced by approximately 10-fold ORP150 expression in hypoxic cultures. These data indicate that cells of the atherosclerotic vessel wall express ORP150 as part of a protective mechanism, potentially triggered by local hypoxia/hypoxemia and augmented by modified lipoproteins. The presence of antibody to ORP150 in sera of patients with severe atherosclerosis emphasizes the possibility that ORP150 may be a marker of vascular pathology.
Phase II Study of Sorafenib in Patients With Sunitinib-Refractory Metastatic Renal Cell Cancer
Authors: Giuseppe Di Lorenzo, Giacomo Cartenì, Riccardo Autorino, Gianni Bruni, Marianna Tudini, Mimma Rizzo, Michele Aieta, Antonio Gonnella, Pasquale Rescigno, Sisto Perdonà, Gianluca Giannarini, Sandro Pignata, Nicola Longo, Giovannella Palmieri, Ciro Imbimbo, Michele De Laurentiis, Vincenzo Mirone, Corrado Ficorella, Sabino De Placido
Journal: Journal of Clinical Oncology (2009)

No previous prospective trials have been reported with sorafenib in patients with sunitinib-refractory metastatic renal cell cancer (MRCC). We conducted a multicenter study to determine the activity and tolerability of sorafenib as second-line therapy after sunitinib progression in MRCC.Between January 2006 and September 2008, 52 patients were enrolled onto this single-arm phase II study. All patients received sorafenib 400 mg orally twice a day until disease progression or intolerable toxicity. The primary end point was objective response rate (complete or partial response) evaluated every 8 weeks by use of the Response Evaluation Criteria in Solid Tumors; secondary end points were toxicity, time to progression (TTP), and overall survival (OS).All patients were included in response and safety analyses. Partial responses were observed in 9.6% of patients (five of 52 patients; 95% CI, 5% to 17%) after two cycles. Grade 1 to 2 fatigue, diarrhea, nausea/vomiting, rash, and neutropenia were the most common side effects, noted in 16 (30.8%), 19 (36.5%), 20 (38.5%), 19 (36.5%), and 20 patients (38.5%), respectively. The most common grade 3 toxicity was diarrhea, noted in six patients (11.5%). Median TTP was 16 weeks (range, 8 to 40 weeks), and median OS was 32 weeks (range, 16 to 64 weeks).Although well tolerated, sorafenib shows limited efficacy in sunitinib-refractory MRCC. Further randomized trials comparing sorafenib with other drugs that target different biologic pathways are needed to define the best second-line treatment option in these patients.
Shared Vulnerabilities in Research
Authors: Eric Chwang
Journal: The American Journal of Bioethics (2014)

The U.S. Code of Federal Regulations governing federally funded research on human subjects assumes that harmful research is sometimes morally justifiable because the beneficiaries of that research share a particular vulnerability with its subjects. In this article, I argue against this assumption, which occurs in every subpart of the Code of Federal Regulations that deals with specific vulnerable populations (pregnant women, fetuses, neonates, prisoners, and children). I argue that shared vulnerability is no exception to the general principle that harming one person in order to benefit another is no more justifiable if the two people have traits in common. Further, shared vulnerability is not a reasonable proxy for any morally relevant desideratum of research, in particular the desire to benefit the worst off, the desire to avoid exploitation, and the desire to use vulnerable populations in research only when necessary.
1143-137 Echocardiographic features of definite infective endocarditis: A French collaborative study on 561 cases
Authors: Christine Selton-Suty, Raymond Roudaut, Yvette Bernard, Pierre Nazeyrollas, Eric Garbarz, François Alla, Thanh Doco-Lecompte, Anne Bouvet, François Vandenesch, Catherine Leport, Bruno Hoen, François Delahaye
Journal: Journal of the American College of Cardiology (2004)
Lack of gene rearrangement and mRNA expression of the beta chain of the T cell receptor in spontaneous rat large granular lymphocyte leukemia lines.
Authors: C W Reynolds, M Bonyhadi, R B Herberman, H A Young, S M Hedrick
Journal: The Journal of Experimental Medicine (1985)

Using the murine cDNA clone for the beta chain of the T cell antigen receptor, we have examined four highly cytotoxic rat large granular lymphocyte (LGL) leukemia lines for the expression of unique rearrangements and mRNA transcription of the genes coding for the T cell antigen receptor. In contrast to normal rat T cells and nine rat T cell lines, the LGL leukemia lines exhibited no detectable gene rearrangements in the beta chain locus after digestion of LGL DNA by four restriction enzymes. Northern blots containing RNA from these LGL tumor lines demonstrated a low level of aberrant or nonrearranged beta chain transcription (less than 10 copies per cell) but virtually no translatable 1.3 kilobase message. These results demonstrate that LGL leukemia lines which mediate both natural killer (NK) and antibody-dependent cell-mediated cytotoxicity (ADCC) activities do not express the beta chain of the T cell receptor. The nature of the NK cell receptor for antigen remains elusive.
691 EFFESTS OF RESPONSE TO INTERFERON THERAPY ON THE PROGRESSION TO DECOMPENSATION IN PATIENTS WITH CHRONIC HEPATITIC B
Authors: M.K. Jang, Y.-H. Chung, E. Yu, H.D. Shin, S.H. Lee, D. Lee, S.E. Kim, Y.-S. Lee, S.H. Kim, S.H. Yang, K.M. Kim, Y.S. Lim, H.C. Lee, Y.S. Lee, D.J. Suh
Journal: Journal of Hepatology (2008)