tbuckley/cabot-search huggingface dataset:
Final report of the phase I/II clinical trial of the E75 (nelipepimut-S) vaccine with booster inoculations to prevent disease recurrence in high-risk breast cancer patients
Authors: E.A. Mittendorf, G.T. Clifton, J.P. Holmes, E. Schneble, D. van Echo, S. Ponniah, G.E. Peoples
Journal: Annals of Oncology (2014)
Michael John Gilkes
Authors: D. I. A. Harden
Journal: BMJ (2015)

After qualifying Michael John Gilkes worked as a ship’s surgeon and station medical officer to South Georgia Island and the Antarctic Whaling Fleet for two years. He retained an interest in the Antarctic and accumulated a huge library on this and many other topics. On returning to the UK, he was house surgeon at the Dreadnought Seamen’s Hospital, after which he trained as an …
Research in the Alcohol Clinic and Around-the-Clock Psychiatric Service of the Massachusetts General Hospital
Authors: MORRIS E. CHAFETZ
Journal: American Journal of Psychiatry (1968)

New patterns of treatment have been developed at Massachusetts General Hospital for alcoholics and other individuals often regarded as "unmotivated" and "unreachable" by traditional techniques. The crisis which brings the patient to the treatment facility is viewed not as the single problem to be resolved but as the means by which chronic psychopathology may be treated. The author describes the research leading to this shift in emphasis from crisis resolution to psychosocial restitution and discusses current investigations designed to extend the approach.
Upregulated TRPC1 Channel in Vascular Injury In Vivo and Its Role in Human Neointimal Hyperplasia
Authors: B. Kumar, K. Dreja, S.S. Shah, A. Cheong, S.-Z. Xu, P. Sukumar, J. Naylor, A. Forte, M. Cipollaro, D. McHugh, P.A. Kingston, A.M. Heagerty, C.M. Munsch, A. Bergdahl, A. Hultgårdh-Nilsson, M.F. Gomez, K.E. Porter, P. Hellstrand, D.J. Beech
Journal: Circulation Research (2006)

Occlusive vascular disease is a widespread abnormality leading to lethal or debilitating outcomes such as myocardial infarction and stroke. It is part of atherosclerosis and is evoked by clinical procedures including angioplasty and grafting of saphenous vein in bypass surgery. A causative factor is the switch in smooth muscle cells to an invasive and proliferative mode, leading to neointimal hyperplasia. Here we reveal the importance to this process of TRPC1, a homolog of Drosophila transient receptor potential. Using 2 different in vivo models of vascular injury in rodents we show hyperplasic smooth muscle cells have upregulated TRPC1 associated with enhanced calcium entry and cell cycle activity. Neointimal smooth muscle cells after balloon angioplasty of pig coronary artery also express TRPC1. Furthermore, human vein samples obtained during coronary artery bypass graft surgery commonly exhibit an intimal structure containing smooth muscle cells that expressed more TRPC1 than the medial layer cells. Veins were organ cultured to allow growth of neointimal smooth muscle cells over a 2-week period. To explore the functional relevance of TRPC1, we used a specific E3-targeted antibody to TRPC1 and chemical blocker 2-aminoethoxydiphenyl borate. Both agents significantly reduced neointimal growth in human vein, as well as calcium entry and proliferation of smooth muscle cells in culture. The data suggest upregulated TRPC1 is a general feature of smooth muscle cells in occlusive vascular disease and that TRPC1 inhibitors have potential as protective agents against human vascular failure.
Traumatic Coronary Artery Dissection
Authors: Nicolas M. Van Mieghem, Sander van Weenen, Gijs Nollen, Jurgen Ligthart, Evelyn Regar, Robert-Jan van Geuns
Journal: Circulation (2013)

A 33-year-old male soccer player started to experience chest discomfort briefly after taking a blow from an opponent's knee into his chest during a dribbling maneuver on the pitch.He completed the game but then consulted a referring hospital because of waxing and waning chest complaints irradiating to his left arm.The ECG demonstrated ST-T-segment changes compatible with inferoposterior ischemia (Figure 1).Cardiac enzyme markers were elevated.Echocardiography confirmed inferior wall hypokinesis.The patient was loaded with aspirin and clopidogrel.He
The Obesity-Cancer Link: Lessons Learned from a Fatless Mouse
Authors: Stephen D. Hursting, Nomeli P. Nunez, Lyuba Varticovski, Charles Vinson
Journal: Cancer Research (2007)

Abstract Current dogma suggests that the positive correlation between obesity and cancer is driven by white adipose tissue that accompanies obesity, possibly through excess secretion of adipokines. Recent studies in fatless A-Zip/F1 mice, which have undetectable adipokine levels but display accelerated tumor formation, suggest that adipokines are not required for the enhanced tumor development. The A-Zip/F-1 mice are also diabetic and display elevated circulating levels of other factors frequently associated with obesity (insulin, insulin-like growth factor-1, and proinflammatory cytokines) and activation of several signaling pathways associated with carcinogenesis. In view of this information, the risk factors underlying the obesity-cancer link need to be revisited. We postulate that the pathways associated with insulin resistance and inflammation, rather than adipocyte-derived factors, may represent key prevention and therapeutic targets for disrupting the obesity-cancer link. [Cancer Res 2007;67(6):2391–3]
Tumor-Infiltrating Foxp3−CD4+CD25+ T Cells Predict Poor Survival in Renal Cell Carcinoma
Authors: Sameer A. Siddiqui, Xavier Frigola, Sandra Bonne-Annee, Maria Mercader, Susan M. Kuntz, Amy E. Krambeck, Shomik Sengupta, Haidong Dong, John C. Cheville, Christine M. Lohse, Christopher J. Krco, W. Scott Webster, Bradley C. Leibovich, Michael L. Blute, Keith L. Knutson, Eugene D. Kwon
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Regulatory T cells (Tregs) have been implicated as inhibitors of antitumoral immunity, and evidence suggests that elimination of Tregs may augment natural and pharmacologic immunity. We tested for the presence of putative Tregs within renal cell carcinoma (RCC) tumors. Experimental Design: We identified 170 patients who underwent radical or partial nephrectomy for clear cell RCC between 2000 and 2002. Specimens were stained with anti-CD4, anti-CD25, and anti-Foxp3 antibodies and examined using confocal microscopy. Associations of CD4+CD25+Foxp3− and CD4+CD25+Foxp3+ T cells with death from RCC were evaluated using Cox proportional hazards regression models. Results: At last follow-up, 46 of 170 patients had died; of these, 37 died from RCC at a median of 1.4 years following nephrectomy (range, 0-4.4). Among the 124 remaining patients, median follow-up was 3.7 years (range, 0-5.7). Forty-three (25.3%) tumors harbored CD4+CD25+Foxp3+ T cells. The presence of Foxp3+ T cells was not significantly associated with RCC death univariately. One hundred forty-three (84.1%) tumors harbored CD4+CD25+Foxp3− T cells. The indicator for ≥10% CD4+CD25+Foxp3− T cells was significantly associated with RCC death univariately [risk ratio (RR), 2.60; 95% confidence interval (95% CI), 1.35-4.98; P = 0.004], after adjusting for tumor B7-H1 expression (RR, 2.53; 95% CI, 1.32-4.85; P = 0.005) and lymphocytic infiltration (RR, 2.53; 95% CI, 1.32-4.87; P = 0.005). Conclusions: Increased presence of CD4+CD25+Foxp3+ T cells was not significantly associated with RCC death. In contrast, CD4+CD25+Foxp3− T cells, which may represent a unique set of Tregs or activated helper T cells, was significantly associated with outcome.
Residual Tumor Resection After High-Dose Chemotherapy in Patients With Relapsed or Refractory Germ Cell Cancer
Authors: O. Rick, C. Bokemeyer, S. Weinknecht, J. Schirren, T. Pottek, J.T. Hartmann, T. Braun, B. Rachud, L. Weißbach, M. Hartmann, W. Siegert, J. Beyer
Journal: Journal of Clinical Oncology (2004)

To assess the role of residual tumor resection performed after high-dose chemotherapy (HDCT) in patients with relapsed or refractory germ cell tumors (GCT).Between July 1987 and October 1999, postchemotherapy resections of residual tumors were performed in 57 patients who had been treated with HDCT for relapsed or refractory GCT and who had achieved a partial remission to this treatment.Complete resections of residual masses were achieved in 52 (91%) of 57 patients who were rendered disease free; in five (9%) of 57 patients, the resections were incomplete. Resection of a single site was performed in 39 (68%) of 57 patients, and the remaining 18 (32%) of 57 patients required interventions at two or more residual tumor sites. Necrosis was found in 22 (38%) of 57 patients, mature teratoma with or without necrosis was found in nine (16%) of 57 patients, and viable cancer with or without additional necrosis or mature teratoma was found in 26 (46%) of 57 patients. Viable cancer consisted either of residual germ cell or undifferentiated cancer in 22 (85%) of 26 patients, with additional non-GCT histologies in the remaining four patients. Patients with viable cancer had a significantly inferior outcome after surgery compared with patients with necrosis and/or mature teratoma even if all cancer was completely resected. Pulmonary lesions with a diameter of more than 2 cm were the only predictive variable for viable cancer in univariate analysis.Resections of all residual tumors should be attempted in patients with relapsed or refractory GCT and partial remissions after HDCT.
Association of Diet, Exercise, and Smoking Modification With Risk of Early Cardiovascular Events After Acute Coronary Syndromes
Authors: Clara K. Chow, Sanjit Jolly, Purnima Rao-Melacini, Keith A.A. Fox, Sonia S. Anand, Salim Yusuf
Journal: Circulation (2010)

Background— Although preventive drug therapy is a priority after acute coronary syndrome, less is known about adherence to behavioral recommendations. The aim of this study was to examine the influence of adherence to behavioral recommendations in the short term on risk of cardiovascular events. Methods and Results— The study population included 18 809 patients from 41 countries enrolled in the Organization to Assess Strategies in Acute Ischemic Syndromes (OASIS) 5 randomized clinical trial. At the 30-day follow-up, patients reported adherence to diet, physical activity, and smoking cessation. Cardiovascular events (myocardial infarction, stroke, cardiovascular death) and all-cause mortality were documented to 6 months. About one third of smokers persisted in smoking. Adherence to neither diet nor exercise recommendations was reported by 28.5%, adherence to either diet or exercise by 41.6%, and adherence to both by 29.9%. In contrast, 96.1% of subjects reported antiplatelet use, 78.9% reported statin use, and 72.4% reported angiotensin-converting enzyme/angiotensin receptor blocker use. Quitting smoking was associated with a decreased risk of myocardial infarction compared with persistent smoking (odds ratio, 0.57; 95% confidence interval, 0.36 to 0.89). Diet and exercise adherence was associated with a decreased risk of myocardial infarction compared with nonadherence (odds ratio, 0.52; 95% confidence interval, 0.4 to 0.69). Patients who reported persistent smoking and nonadherence to diet and exercise had a 3.8-fold (95% confidence interval, 2.5 to 5.9) increased risk of myocardial infarction/stroke/death compared with never smokers who modified diet and exercise. Conclusions— Adherence to behavioral advice (diet, exercise, and smoking cessation) after acute coronary syndrome was associated with a substantially lower risk of recurrent cardiovascular events. These findings suggest that behavioral modification should be given priority similar to other preventive medications immediately after acute coronary syndrome. Clinical Trial Registration Information— URL: http://clinicaltrials.gov/ct2/show/NCT00139815. Unique identifier: NCT00139815.
STUDIES ON X-RAY EFFECTS
Authors: Robert T. Hance, James B. Murphy
Journal: The Journal of Experimental Medicine (1926)

1. Hard x-rays prevent the formation of pigment in the hair follicles of mice, with result that hair previously black comes in white. 2. Exposure of the ventral side of a mouse to the x-rays causes the hair on the back to come in white about 40 to 50 days after it has whitened the hairs on the abdomen.
HMGA2 Is a Driver of Tumor Metastasis
Authors: Asahiro Morishita, M. Raza Zaidi, Akira Mitoro, Devipriya Sankarasharma, Matthias Szabolcs, Yasunori Okada, Jeanine D'Armiento, Kiran Chada
Journal: Cancer Research (2013)

The non-histone chromatin-binding protein HMGA2 is expressed predominantly in the mesenchyme before its differentiation, but it is also expressed in tumors of epithelial origin. Ectopic expression of HMGA2 in epithelial cells induces epithelial-mesenchymal transition (EMT), which has been implicated in the acquisition of metastatic characters in tumor cells. However, little is known about in vivo modulation of HMGA2 and its effector functions in tumor metastasis. Here, we report that HMGA2 loss of function in a mouse model of cancer reduces tumor multiplicity. HMGA2-positive cells were identified at the invasive front of human and mouse tumors. In addition, in a mouse allograft model, HMGA2 overexpression converted nonmetastatic 4TO7 breast cancer cells to metastatic cells that homed specifically to liver. Interestingly, expression of HMGA2 enhanced TGFβ signaling by activating expression of the TGFβ type II receptor, which also localized to the invasive front of tumors. Together our results argued that HMGA2 plays a critical role in EMT by activating the TGFβ signaling pathway, thereby inducing invasion and metastasis of human epithelial cancers.
Ventricular Enlargement in Schizophrenia Related to Volume Reduction of the Thalamus, Striatum, and Superior Temporal Cortex
Authors: Christian Gaser, Igor Nenadic, Bradley R Buchsbaum, Erin A Hazlett, Monte S Buchsbaum
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: Enlargement of the lateral ventricles is among the most frequently reported macroscopic brain structural changes in schizophrenia, although variable in extent and localization. The authors investigated whether ventricular enlargement is related to regionally specific volume loss. METHOD: High-resolution magnetic resonance imaging scans from 39 patients with schizophrenia were analyzed with deformation-based morphometry, a voxel-wise whole brain morphometric technique. RESULTS: Significant negative correlations with the ventricle-brain ratio were found for voxels in the left and right thalamus and posterior putamen and in the left superior temporal gyrus and insula. CONCLUSIONS: Thalamic shrinkage, especially of medial nuclei and the adjacent striatum and insular cortex, appear to be important contributors to ventricular enlargement in schizophrenia.
MECHANISMS BY WHICH CARDIAC RESYNCHRONIZATION THERAPY IMPROVES CARDIAC PERFORMANCE IN HEART FAILURE
Authors: Lynne K. Williams, Susan M. Ellery, Fransisco Leyva-Leon, Kiran C. Patel, Robert A. Bleasdale, Berthold Stegemann, Vince Paul, Paul Steendijk, Michael P. Frenneaux
Journal: Journal of the American College of Cardiology (2011)
The Hallucinogenic Drugs—Curse or Blessing?
Authors: STEPHEN SZARA
Journal: American Journal of Psychiatry (1967)

The hallucinogens are divided into three groups: adrenaline-related, tryptamine-related, and miscellaneous, and their chemistry is reviewed. The author points out the limitations of the biochemical and classical pharmacological approaches to understanding the varieties of psychological responses to the drugs. He urges that we view the function of the central nervous system in terms of structure, chemistry, and information so that we can better comprehend and predict psychological reactions to the drugs.
Failure of Iniparib to Inhibit Poly(ADP-Ribose) Polymerase <i>In Vitro</i>
Authors: Anand G. Patel, Silvana B. De Lorenzo, Karen S. Flatten, Guy G. Poirier, Scott H. Kaufmann
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Poly(ADP-ribose) polymerase (PARP) inhibitors are undergoing extensive clinical testing for their single-agent activity in homologous recombination (HR)-deficient tumors and ability to enhance the action of certain DNA-damaging agents. Compared with other PARP inhibitors in development, iniparib (4-iodo-3-nitrobenzamide) is notable for its simple structure and the reported ability of its intracellular metabolite 4-iodo-3-nitrosobenzamide to covalently inhibit PARP1 under cell-free conditions. The present preclinical studies were conducted to compare the actions iniparib with the more extensively characterized PARP inhibitors olaparib and veliparib. Experimental Design: The abilities of iniparib, olaparib, and veliparib to (i) selectively induce apoptosis or inhibit colony formation in HR-deficient cell lines, (ii) selectively sensitize HR-proficient cells to topoisomerase I poisons, and (iii) inhibit formation of poly(ADP-ribose) polymer (pADPr) in intact cells were compared. Results: Consistent with earlier reports, olaparib and veliparib selectively induced apoptosis and inhibited colony formation in cells lacking BRCA2 or ATM. Moreover, like earlier generation PARP inhibitors, olaparib and veliparib sensitized cells to the topoisomerase I poisons camptothecin and topotecan. Finally, olaparib and veliparib inhibited formation of pADPr in intact cells. In contrast, iniparib exhibited little or no ability to selectively kill HR-deficient cells, sensitize cells to topoisomerase I poisons, or inhibit pADPr formation in situ. In further experiments, iniparib also failed to sensitize cells to cisplatin, gemcitabine, or paclitaxel. Conclusions: While iniparib kills normal and neoplastic cells at high (&amp;gt;40 μmol/L) concentrations, its effects are unlikely to reflect PARP inhibition and should not be used to guide decisions about other PARP inhibitors. Clin Cancer Res; 18(6); 1655–62. ©2012 AACR.
Initial Microbiologic Studies Did Not Affect Outcome in Adults Hospitalized with Community-Acquired Pneumonia
Authors: SAUGATO SANYAL, PETER R. SMITH, ANIMITA C. SAHA, SASWATI GUPTA, LEONARD BERKOWITZ, PETER HOMEL
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Microbiologic studies (MBSs) fail to identify a specific pathogen in more than 50% of patients with community-acquired pneumonia (CAP). The 1993 American Thoracic Society guideline (ATS-GL) for the management of CAP advised selecting initial antibiotic regimens based on severity of illness and comorbidities. Our study evaluated the role of initial MBS in adult patients hospitalized with CAP and treated according to the ATS-GL. In 184 patients hospitalized at our facility for CAP in 1996, and treated according to the ATS-GL, 25 (14%) failed to respond to initial antibiotic regimens. In these nonresponders, there was no difference in mortality between those in whom antibiotics were changed empirically, and those with MBS-guided changes. We conclude that initial MBS may not be warranted in many adult patients admitted for CAP. Exceptions include patients with conditions that predispose to less common, more resistant pathogens.
Putative Mechanisms of Toxicity of 3-Methylindole: From Free Radical to Pneumotoxicosis
Authors: T M Bray, K S Emmerson
Journal: The Annual Review of Pharmacology and Toxicology (1994)

Heme oxygenases (HO) catabolize free heme, that is, iron (Fe) protoporphyrin (IX), into equimolar amounts of Fe2+, carbon monoxide (CO), and biliverdin. The stress-responsive HO-1 isoenzyme affords protection against programmed cell death. The mechanism ...Read More
Expansion of immunoglobulin-secreting cells and defects in B cell tolerance in <i>Rag</i>-dependent immunodeficiency
Authors: Jolan E. Walter, Francesca Rucci, Laura Patrizi, Mike Recher, Stephan Regenass, Tiziana Paganini, Marton Keszei, Itai Pessach, Philipp A. Lang, Pietro Luigi Poliani, Silvia Giliani, Waleed Al-Herz, Morton J. Cowan, Jennifer M. Puck, Jack Bleesing, Tim Niehues, Catharina Schuetz, Harry Malech, Suk See DeRavin, Fabio Facchetti, Andrew R. Gennery, Emma Andersson, Naynesh R. Kamani, JoAnn Sekiguchi, Hamid M. Alenezi, Javier Chinen, Ghassan Dbaibo, Gehad ElGhazali, Adriano Fontana, Srdjan Pasic, Cynthia Detre, Cox Terhorst, Frederick W. Alt, Luigi D. Notarangelo
Journal: The Journal of Experimental Medicine (2010)

The contribution of B cells to the pathology of Omenn syndrome and leaky severe combined immunodeficiency (SCID) has not been previously investigated. We have studied a mut/mut mouse model of leaky SCID with a homozygous Rag1 S723C mutation that impairs, but does not abrogate, V(D)J recombination activity. In spite of a severe block at the pro–B cell stage and profound B cell lymphopenia, significant serum levels of immunoglobulin (Ig) G, IgM, IgA, and IgE and a high proportion of Ig-secreting cells were detected in mut/mut mice. Antibody responses to trinitrophenyl (TNP)-Ficoll and production of high-affinity antibodies to TNP–keyhole limpet hemocyanin were severely impaired, even after adoptive transfer of wild-type CD4+ T cells. Mut/mut mice produced high amounts of low-affinity self-reactive antibodies and showed significant lymphocytic infiltrates in peripheral tissues. Autoantibody production was associated with impaired receptor editing and increased serum B cell–activating factor (BAFF) concentrations. Autoantibodies and elevated BAFF levels were also identified in patients with Omenn syndrome and leaky SCID as a result of hypomorphic RAG mutations. These data indicate that the stochastic generation of an autoreactive B cell repertoire, which is associated with defects in central and peripheral checkpoints of B cell tolerance, is an important, previously unrecognized, aspect of immunodeficiencies associated with hypomorphic RAG mutations.
Collaborative Research in Childhood Cancer Survivorship: The Current Landscape
Authors: Smita Bhatia, Saro H. Armenian, Gregory T. Armstrong, Eline van Dulmen-den Broeder, Michael M. Hawkins, Leontien C.M. Kremer, Claudia E. Kuehni, Jørgen H. Olsen, Leslie L. Robison, Melissa M. Hudson
Journal: Journal of Clinical Oncology (2015)

Survivors of childhood cancer carry a substantial burden of morbidity and are at increased risk for premature death. Furthermore, clear associations exist between specific therapeutic exposures and the risk for a variety of long-term complications. The entire landscape of health issues encountered for decades after successful completion of treatment is currently being explored in various collaborative research settings. These settings include large population-based or multi-institutional cohorts and single-institution studies. The ascertainment of outcomes has depended on self-reporting, linkage to registries, or clinical assessments. Survivorship research in the cooperative group setting, such as the Children's Oncology Group, has leveraged the clinical trials infrastructure to explore the molecular underpinnings of treatment-related adverse events, and to understand specific complications in the setting of randomized risk-reduction strategies. This review highlights the salient findings from these large collaborative initiatives, emphasizing the need for life-long follow-up of survivors of childhood cancer, and describing the development of several guidelines and efforts toward harmonization. Finally, the review reinforces the need to identify populations at highest risk, facilitating the development of risk prediction models that would allow for targeted interventions across the entire trajectory of survivorship.