tbuckley/cabot-search huggingface dataset:
Distinctive Features of the Differentiated Phenotype and Infiltration of Tumor-Reactive Lymphocytes in Clear Cell Renal Cell Carcinoma
Authors: Qiong J. Wang, Ken-ichi Hanada, Paul F. Robbins, Yong F. Li, James C. Yang
Journal: Cancer Research (2012)

Clear cell renal cell carcinoma (RCC) is considered an immunogenic tumor, but it has been difficult to identify tumor-infiltrating lymphocytes (TIL) that show in vitro tumor recognition. We compared the characteristics of fresh RCC TIL to peripheral blood lymphocytes (PBL) or melanoma TIL. Our results showed that RCC TIL contained fewer CD27(+) T cells, and fewer naïve and central memory (CM) T cells, but more effector memory (EM) T cells than melanoma TIL or renal PBL. We hypothesized that factors in the RCC microenvironment were skewing TIL phenotype toward EM. One possibility was the expression of CD70 on nearly all human RCCs, but not melanomas. Differentiation of naïve T cells to EM cells only occurred from CD70 costimulation in concert with T-cell receptor (TCR) stimulation (signal one), suggesting that EM TIL responding to CD70 would be enriched for T cells reactive with local antigens, including those associated with RCC. Clonotypic analysis of TCRs in fresh RCCs showed that EM T cells were more clonally expanded than CM or naïve T cells, and the clonal expansion occurred at the tumor site as oligoclonal TCRs were distinct from PBL TCRs from the same patient. In addition, we found that 2 TCRs from the highly represented EM TIL clones, when reexpressed in fresh PBL, recognized an MHC-class II or MHC-class I-restricted antigens shared by multiple RCC lines. Our results suggest that RCC-reactive TIL do exist in situ, but may be difficult to recover and study because of proliferative exhaustion, driven by tumor-expressed CD70.
Familial palindromic rheumatism: a possible association with HLA.
Authors: A Pines, N Kaplinsky, S Orgad, E Gazit, O Frankl
Journal: Annals of the Rheumatic Diseases (1983)

Palindromic rheumatism is very rare in children. The familial occurrence of the disease has been only briefly reported previously. A family is described here in which the mother and her 3 children suffered from typical palindromic rheumatism, which ran a benign course. All 4 members were seronegative and the HLA types of the children were identical. The HLA genotype of the mother was HLA A2, Cw4, Bw41, Bw6, DR5, MT2/Aw32, CX, Bw44, Bw4, DR1, MT1. HLA DR5 has previously been found to be associated with juvenile rheumatoid arthritis, while DR1 in Jews is significantly associated with adult-onset rheumatoid arthritis. DR5 was shared by the mother and her 3 children. The presence of the antigen DR5 in this sibship suggests that palindromic rheumatism may be a variant of juvenile rheumatoid arthritis with a relatively late onset and a more benign course. Tissue typing of patients with palindromic rheumatism may give a clue to prognosis. The patients9 youth and the familial involvement, with identical HLA characteristics, are the outstanding features of this family.
Hepatocyte Growth Factor Attenuates Collagen Accumulation in a Murine Model of Pulmonary Fibrosis
Authors: MAKOTO DOHI, TAKASHI HASEGAWA, KAZUHIKO YAMAMOTO, BRUCE C. MARSHALL
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

We investigated the in vivo effects of recombinant human hepatocyte growth factor (HGF) on epithelial cell proliferation in normal mouse lung and on the repair process that follows bleomycin-induced lung injury. Intratracheal administration of 100 μ g of rhHGF to C57BL/6 mice led to proliferation of bronchial and alveolar epithelial cells as indicated by an increased number of cells staining for proliferating cell nuclear antigen (PCNA). The effect of HGF on the lung repair process was examined by administration of 100 μ g of rhHGF on Day 3 and Day 6 after intratracheal injection of bleomycin to mice. We found that HGF significantly attenuated collagen accumulation induced by bleomycin as determined by quantitation of hydroxyproline content and by scoring of the extent of fibrosis. To explore the potential mechanisms involved in the beneficial effects of HGF, we performed in vitro studies with A549 pulmonary epithelial cells and found that HGF enhanced cell surface plasmin generation, expression of u-PA activity, and cell migration. In summary, HGF has potent in vivo and in vitro effects on epithelial cells, which suggests it may have a role in the therapy of pulmonary fibrosis.
Rating information on the internet can empower users to make informed decisions
Authors: G. Eysenbach
Journal: BMJ (1999)

EDITOR—Last year Diepgen and I proposed rating information on the internet with a standard vocabulary of machine-readable metadata.1 In his comment on our paper Whatling incorrectly implied that we intend to “dismiss the input of non-medical readers.”2 This is a misunderstanding—we merely aim to empower users to make informed decisions.

I would not call the efforts of physicians to evaluate information on the internet “arrogant.” Using that argument, it would be arrogant for peer reviewers for scientific journals to assess …
A National Survey of Stress Reactions after the September 11, 2001, Terrorist Attacks
Authors: Mark A. Schuster, Bradley D. Stein, Lisa H. Jaycox, Rebecca L. Collins, Grant N. Marshall, Marc N. Elliott, Annie J. Zhou, David E. Kanouse, Janina L. Morrison, Sandra H. Berry
Journal: New England Journal of Medicine (2001)

People who are not present at a traumatic event may experience stress reactions. We assessed the immediate mental health effects of the terrorist attacks on September 11, 2001.
Associations of atherosclerotic risk factors and coronary artery disease with plaques in thoracic and abdominal aorta detected by magnetic resonance imaging
Authors: Yukihiko Momiyama, Hiroaki Taniguchi, Reiko Ohmori, Akiko Hara, Kou Arakawa, Noboru Kameyama, Kiyoshi Nagasawa, Masayoshi Nagata, Haruo Nakamura, Fumitaka Ohsuzu
Journal: Journal of the American College of Cardiology (2002)
Gross motor performance and the educationally sub-normal child [proceedings]
Authors: L. Burwitz, P. W. Harrison, B. Davies, A. Daggett, J. Montgomery
Journal: British Journal of Sports Medicine (1977)

The present study is part of a long-term inter- disciplinary project designed to study the apparent dif- ference between normal and educationally sub-normal children (ESN) on tests that measure gross motor per-
Effects of Red-Cell Storage Duration on Patients Undergoing Cardiac Surgery
Authors: Marie E. Steiner, Paul M. Ness, Susan F. Assmann, Darrell J. Triulzi, Steven R. Sloan, Meghan Delaney, Suzanne Granger, Elliott Bennett-Guerrero, Morris A. Blajchman, Vincent Scavo, Jeffrey L. Carson, Jerrold H. Levy, Glenn Whitman, Pamela D’Andrea, Shelley Pulkrabek, Thomas L. Ortel, Larissa Bornikova, Thomas Raife, Kathleen E. Puca, Richard M. Kaufman, Gregory A. Nuttall, Pampee P. Young, Samuel Youssef, Richard Engelman, Philip E. Greilich, Ronald Miles, Cassandra D. Josephson, Arthur Bracey, Rhonda Cooke, Jeffrey McCullough, Robert Hunsaker, Lynne Uhl, Janice G. McFarland, Yara Park, Melissa M. Cushing, Charles T. Klodell, Ravindra Karanam, Pamela R. Roberts, Cornelius Dyke, Eldad A. Hod, Christopher P. Stowell
Journal: New England Journal of Medicine (2015)

Some observational studies have reported that transfusion of red-cell units that have been stored for more than 2 to 3 weeks is associated with serious, even fatal, adverse events. Patients undergoing cardiac surgery may be especially vulnerable to the adverse effects of transfusion.We conducted a randomized trial at multiple sites from 2010 to 2014. Participants 12 years of age or older who were undergoing complex cardiac surgery and were likely to undergo transfusion of red cells were randomly assigned to receive leukocyte-reduced red cells stored for 10 days or less (shorter-term storage group) or for 21 days or more (longer-term storage group) for all intraoperative and postoperative transfusions. The primary outcome was the change in Multiple Organ Dysfunction Score (MODS; range, 0 to 24, with higher scores indicating more severe organ dysfunction) from the preoperative score to the highest composite score through day 7 or the time of death or discharge.The median storage time of red-cell units provided to the 1098 participants who received red-cell transfusion was 7 days in the shorter-term storage group and 28 days in the longer-term storage group. The mean change in MODS was an increase of 8.5 and 8.7 points, respectively (95% confidence interval for the difference, -0.6 to 0.3; P=0.44). The 7-day mortality was 2.8% in the shorter-term storage group and 2.0% in the longer-term storage group (P=0.43); 28-day mortality was 4.4% and 5.3%, respectively (P=0.57). Adverse events did not differ significantly between groups except that hyperbilirubinemia was more common in the longer-term storage group.The duration of red-cell storage was not associated with significant differences in the change in MODS. We did not find that the transfusion of red cells stored for 10 days or less was superior to the transfusion of red cells stored for 21 days or more among patients 12 years of age or older who were undergoing complex cardiac surgery. (Funded by the National Heart, Lung, and Blood Institute; RECESS ClinicalTrials.gov number, NCT00991341.).
Suicide After Childhood Cancer
Authors: Regan A. Howard, Peter D. Inskip, Lois B. Travis
Journal: Journal of Clinical Oncology (2007)

TO THE EDITOR: Dr Recklitis et al report suicidal symptoms in a significant number of adult survivors of childhood cancer and identify risk factors associated with these symptoms. Although the authors do not report risk estimates for suicide in this patient population, their results suggest that adult survivors of childhood cancer are at an elevated risk for suicidality, even many years after treatment. Herein, we provide the first report of an increased risk of suicide in a large, population-based cohort of childhood cancer survivors in the United States. We identified 35,814 children diagnosed with cancer before age 21 years between 1973 and 2003 and reported to one of nine registries in the Surveillance, Epidemiology, and End Results program. Previous population-based follow-up studies of patients diagnosed with cancer at all ages taken together found 1.3to 2.9-fold standardized mortality ratios (SMRs) of suicide; however, separate risk estimates for childhood cancer survivors were not provided. Investigations of survivors of childhood cancer have been limited to hospital or clinical series. In our study, 36 childhood cancer survivors committed suicide (SMR 11; 95% CI, 7.8 to 15.3; excess absolute risk (EAR) 10 per 100,000 person-years). The median duration between initial cancer diagnosis and suicide was 10 years (range, 0.7 to 22 years). The median age at suicide was 26.8 years (range, 15.8 to 35.5 years). Significantly elevated SMRs of 11.7, 5.9, 13.8, and 11.7 were observed less than 1 year, 1 to 4 years, 5 to 9 years, and 10 or more years after initial cancer diagnosis, with no evidence of a diminution in risk with time. Risk for patients diagnosed with cancer at ages 10 to 14 years (SMR 12.9; 95% CI, 5.6 to 25.4) and 15 to 20 years (SMR 12.1; 95% CI, 7.7 to 17.9) was higher than those diagnosed at younger ages (0 to 4 years, SMR 3.26; 95% CI, 0.0 to 18.1; 5 to 9 years, SMR 8.8; 95% CI, 1.8 to 25.8). Suicide risk was comparable for males (SMR 10.9; 95% CI, 7.3 to 15.6) and females (SMR 11.8; 95% CI, 4.7 to 24.4). SMRs were similar for patients diagnosed before 1985 (SMR 11.9; 95% CI, 7.8 to 17.5) and those diagnosed in subsequent calendar years (SMR 9.2; 95% CI, 4.4 to 17.0). Risk was not higher for patients initially treated with radiation (SMR 9.8; 95% CI, 5.2 to 16.8) compared with those who did not receive radiotherapy as part of the primary therapy (SMR 11.9; 95% CI, 7.5 to 17.8). Although suicide among childhood cancer survivors is a rare event, the significantly elevated risk in this population-based survey is noteworthy. Our findings are consistent with those observed by Recklitis et al. Survivors of childhood cancer not only report an increased number of suicidal symptoms, but they also are at an increased risk of suicide. These results underscore the importance of incorporating resources devoted to psychosocial concerns into long-term follow-up programs for childhood cancer survivors.
Continuous 12-lead ST-segment recovery analysis in the TAMI 7 study. Performance of a noninvasive method for real-time detection of failed myocardial reperfusion.
Authors: M W Krucoff, M A Croll, J E Pope, C B Granger, C M O'Connor, K N Sigmon, B L Wagner, J A Ryan, K L Lee, D J Kereiakes
Journal: Circulation (1993)

BACKGROUND If a practical, reliable, noninvasive marker of failed reperfusion was available in real time, the benefits of further therapy in this patient subgroup could be tested. We developed a method of 12-lead ST-segment recovery analysis using continuously updated reference points to provide such a marker. METHODS AND RESULTS In this study, our method was prospectively tested in 144 patients given thrombolytic therapy early in myocardial infarction. All patients had 12-lead continuous ST-segment monitoring and acute angiography, each analyzed in an independent, blinded core laboratory. ST-segment recovery and re-elevation were analyzed up to the moment of angiography, at which time patency was predicted. Predictions were correlated to angiographic infarct artery flow, with TIMI flow 0 to 1 as occluded and TIMI flow 2 to 3 as patent. Infarct artery occlusion was seen on first injection in 27% of patients. The positive predictive value of incomplete ST recovery or ST re-elevation by our method was 71%, negative predictive value 87%, with 90% specificity and 64% sensitivity for coronary occlusion. ST recovery analysis predicted patency in 94% of patients with TIMI 3 flow versus 81% of patients with TIMI 2 flow and predicted occlusion in 57% of patients with collateralized occlusion versus 72% of patients with non-collateralized occlusion. In a regression model including other noninvasive clinical descriptors, ST recovery alone contained the vast majority of predictive information about patency. CONCLUSIONS In a blinded, prospective, angiographically correlated study design, 12-lead continuous ST-segment recovery analysis shows promise as a practical noninvasive marker of failed reperfusion that may contribute substantially to currently available bedside assessment. Our data also suggest that patients with TIMI 2 flow or with collateralized occlusions may represent a physiological spectrum definable with ST-segment recovery analysis.
Abstract 4394: Development of parallel conjugation and assay methodologies to screen for antibodies with optimal properties for use as antibody-drug conjugates
Authors: Robert P. Lyon, Maureen C. Ryan, May Sutherland, Brad Meyer, Changpu Yu, Heather Kostner, Jamie Miyamoto, Dennis R. Benjamin
Journal: Cancer Research (2010)

Abstract The activity of antibody-drug conjugates (ADCs) on cancer cells can be affected by a multitude of factors, such as binding affinity, rate of internalization, subcellular trafficking, and efficient drug release within the target cell population. Consequently, the properties of an ideal antibody for drug delivery are not necessarily the same as those for a therapeutic naked antibody. Furthermore, the use of indirect assays involving the use of secondary antibodies to screen for optimal ADCs can be misleading, since crosslinking on the cell surface can lead to altered downstream events, and the affinity of the secondary antibody constrains the dynamic range of the assay. When seeking candidate antibodies directed against a novel antigen for ADC therapy, it is therefore most desirable to screen a large panel in the form of ADCs and evaluate their cytotoxic activities, since these results provide a direct measurement of parameters that can affect cytotoxic activity. However, when dealing with microgram quantities of a large number of antibodies as is typical of an antibody discovery campaign, the yields from conventional conjugation methodologies are limiting. We developed a novel approach that addresses this issue and have successfully applied it to the discovery of optimal ADCs out of a large panel of candidate antibodies. The technology is currently being applied to the discovery of ADCs against antigens of interest for targeted drug delivery. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4394.
Activation of the Fanconi Anemia/BRCA Pathway and Recombination Repair in the Cellular Response to Solar Ultraviolet Light
Authors: Jessica Dunn, Marisa Potter, Adam Rees, Thomas M. Rünger
Journal: Cancer Research (2006)

Abstract Recombination repair plays an important role in the processing of DNA double-strand breaks (DSB) and DNA cross-links, and has been suggested to be mediated by the activation of the Fanconi anemia (FA)/BRCA pathway. Unlike DNA damage generated by ionizing radiation or DNA cross-linking, UV light–induced DNA damage is not commonly thought to require recombination for processing, as UV light does not directly induce DSBs or DNA cross-links. To elucidate the role of recombination repair in the cellular response to UV, we studied the FA/BRCA pathway in primary skin cells exposed to solar–simulated light. UV-induced monoubiquitination of the FANCD2 protein and formation of FANCD2 nuclear foci confirmed the activation of the pathway by UV light. This was only observed when cells were irradiated during S phase and was not caused by directly UV-induced DSBs. UV-exposed cells did not exhibit FANCD2 nuclear foci once they entered mitosis or when growth-arrested. In addition, UV-induced nuclear foci of the recombination proteins, RAD51 and BRCA1, colocalized with FANCD2 foci. We suggest that in response to UV light, when nucleotide excision repair failed to repair, or when translesional DNA synthesis failed to bypass UV-induced DNA photoproducts, the FA/BRCA pathway mediates the recombination repair of replication forks stalled at DNA photoproducts as a third line of defense. (Cancer Res 2006; 66(23): 11140-7)
Research Training of Residents in a Community Hospital
Authors: Alvan G. Foraker
Journal: New England Journal of Medicine (1963)

IN 1955, when the Baptist Memorial Hospital of Jacksonville opened, an effort was made to establish a medical research program. In 1957 emphasis on supervised research was made an intrinsic part of the nascent residency in pathology. It was believed that research can be taught, just as pathological anatomy and clinical pathology are taught. The technics employed in an individual study may soon become obsolete. Nevertheless, certain principles remain constant, including a system of approach to and analysis of the problem, intellectual self-discipline, meticulous work and record keeping. The program also emphasizes literature review, analysis and criticism of results and . . .
Velocity and direction in neurobehavioral evolution: The centripetal prospective
Authors: Robert R. Provine
Journal: Behavioral and Brain Sciences (2006)

Selection for or against muscle initiates a cascade of centripetal (outside-in), trophically mediated, neurological events through which the environment programs heritable neuromuscular and neuroneuronal connections in a rapid and specific fashion. The velocity, direction, and efficiency of this process are a consequence of the environment acting directly on muscle, the organ of action, and behavioral interface between organism and environment.
Abstract 209: Gamma linolenic acid sensitizes pancreatic cancer cells to chemotherapy
Authors: Ingrid C. Espinoza, Robert Busby, Ruth Lupu
Journal: Cancer Research (2010)

Abstract In pancreatic cancer both chemotherapy and radiotherapy have shown deficient results in treating the disease, indicating a fundamental need for more efficient therapies. Most pancreatic cancer patients present with an advanced form of the disease that is incurable by surgery, and will receive palliative treatment in the form of surgery, chemotherapy, radiotherapy and symptom control. There are few standard chemotherapeutics for the treatment of pancreatic cancer, although Gemcitabine and 5-Fluorouracil (5-FU) are the most widely used. In search for specific nutritional, and/or pharmacological agents to target pancreatic cancer cells/tissues we identified a series of nutritional supplements known as polyunsaturated fatty acids (PUFAs) that have an inhibitory effect on cancer cells. However, Gamma-Linolenic-Acid (GLA), a member of the ω-6 family of PUFAs exerts selective cytotoxic effects on pancreatic cancer cells without affecting normal epithelial cells. The goal of our study was to determine whether GLA could sensitize the targeted pancreatic cancer cells to chemotherapeutic agents (Gemcitabine or 5-FU). Therefore, pancreatic cancer cells were treated initially with GLA followed by each of the chemotherapeutic agents separately: Our results demonstrated that: 1) GLA induced growth inhibition and apoptosis of pancreatic cancer cells (Panc-1 and BxPC3); 2) the combination of GLA and Gemcitabine or GLA and 5-FU: a) promote a synergistic inhibitory effect on the growth of pancreatic cancer cells; b) inhibition of anchorage-independent growth; and 4) inhibition of morphogenesis in 3-D matrigel culture. These results show that GLA increases the sensitivity of pancreatic cancer cells to chemotherapy through a synergistic effect with Gemcitabine or 5-FU, implying that GLA could be used as a supportive drug for the pancreatic cancer patients receiving the current chemotherapeutic regimens. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 209.