tbuckley/cabot-search huggingface dataset:
Abstract 324: Dronedarone Alters the Sensitivity of Cardiac Mitochondria to Permeability Transition Pore Opening
Authors: Sirisha Gudlawar, Milanka Cosic, Farhan Rizvi, Ekhson Holmuhamedov, Monika Thakur, Mahek Mirza, Jamil Tajik, Francis Dawney, Arshad Jahangir
Journal: Circulation Research (2014)

Introduction: Dronedarone (DR) is a new antiarrhythmic agent that was design to minimize side effects of Amiodarone. However, in clinical trials was shown to worsen heart failure (HF) and increased mortality. The mechanisms for these adverse effects are not known. Since mitochondria are critical for maintaining cardiac energetics and regulate, we hypothesized that DR increases sensitivity towards opening of mitochondrial permeability transition pore (mPTP) that underlies mitochondrial failure and cell death. Methods: Mitochondria were isolated from left atrial appendage tissue of patients undergoing bypass cardiac surgery (n=3). Patients did not have any history of HF or atrial fibrillation. To induce mPTP, mitochondria were exposed with sequential additions of Ca 2+ (Fluo-5N) in the presence of 5, 10, 20 μM of DR. The opening of mPTP was determined by monitoring abrupt release of Ca 2+ , rapid loss of membrane potential (ΔΨ) and mitochondrial swelling. Results: DR accelerated Ca 2+ -induced mPTP opening starting at 5 μM concentration (Fig). At concentration of 20 μM, it completely depolarized mitochondria abolishing capacity for Ca 2+ handling and responsiveness to cyclosporine A (CsA), an inhibitor of mPTP. Conclusion: In isolated human cardiac mitochondria from patients without history of HF DR at clinically relevant concentration increased sensitivity of mitochondria to Ca 2+ induced mPTP opening. In failing heart this can be compromised and needs to be studied. Dronedarone accelerates Ca 2+ -induced mPTP opening in mitochondria isolated from human left atrial appendage.
Critique of the Danish-American studies of the biological and adoptive relatives of adoptees who became schizophrenic
Authors: T Lidz, S Blatt
Journal: American Journal of Psychiatry (1983)

The authors present various reasons why their analysis of the data provided by the Danish-American studies of the relatives of adoptees who became schizophrenic demonstrates that the data do not support the investigators' claims that their studies provide conclusive evidence of a significant genetic factor in the etiology of schizophrenia. When taken together with the authors' earlier demonstration that the investigators' more direct study of the adopted-away offspring of schizophrenic parents failed to provide statistically significant evidence of a genetic influence, these adoption studies indicate that although genetic factors may play some role in the etiology of chronic schizophrenic disorders, such findings are far from definite or proven.
Abstract P4-09-05: Expression of breast cancer stem cell marker as a predictor of prognosis and response to trastuzumab in HER2-positive breast cancer
Authors: AN Seo, HJ Lee, EJ Kim, MH Jang, YJ Kim, JH Kim, S-W Kim, HS Ryu, IA Park, S-A Im, G Gong, KH Jung, SY Park
Journal: Cancer Research (2016)

Abstract BACKGROUND: Breast cancer stem cells (BCSCs) have been suggested to have clinical implications for cancer therapeutics because of its proposed role in chemoresistance. The aim of this study was to investigate the impact of BCSC marker expression in clinical outcome and trastuzumab response HER2-postive breast cancer. METHODS: We analyzed the clinical significance of BCSC marker (ALDH1 and CD44+/CD24-) expression in 242 HER2-positive primary breast cancers using immunohistochemistry. In addition, we examined the relationship between BCSC marker expression, trastuzumab response and clinical outcome in 447 primary, and 112 metastatic HER2-positive breast cancer patients treated by trastuzumab. RESULTS: In the first set, ALDH1 positivity and CD44+/CD24- phenotype were detected in 10.0% and 29.9%, respectively. ALDH1 positivity and CD44+/CD24- phenotype correlated with hormone receptor negativity. In survival analyses, CD44+/CD24- phenotype, but not ALDH-1 expression, was found to be an independent prognostic factor for poor disease-free and overall survival of patients in entire group, and in subgroup not receiving trastuzumab. In HER2-positive primary breast cancer patients treated by adjuvant trastuzumab, CD44+/CD24- phenotype was also an independent poor prognostic factor for disease-free survival. However, ALDH1 positivity and CD44+/CD24- phenotype had no effect on trastuzumab response and survival in patients with metastatic HER2 positive breast cancer. CONCLUSION: These results suggest that CD44+/CD24- phenotype can be used as a prognostic factor for clinical outcome and a predictive factor of trastuzumab response in patients with HER2-positive primary breast cancer. Citation Format: Seo AN, Lee HJ, Kim EJ, Jang MH, Kim YJ, Kim JH, Kim S-W, Ryu HS, Park IA, Im S-A, Gong G, Jung KH, Park SY. Expression of breast cancer stem cell marker as a predictor of prognosis and response to trastuzumab in HER2-positive breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-09-05.
Obstacles to utilization of prepaid mental health care
Authors: M A Glasser, T J Duggan, W S Hoffman
Journal: American Journal of Psychiatry (1975)

The coverage of out-of-hospital expenses for mental health care through prepayment and insurance programs has been a major advance in removing the economic barriers to early detection, diagnosis, and treatment of mental disorders. However, obstacles to obtaining treatment block many eligible people from receiving help. The authors conducted a study among members of the United Auto Workers union to identify these roadblocks. Among the obstacles were differences in perceptions of need for treatment and in attitudes toward treatment, and lack of awareness of eligibility for benefits among three key groups - consumers, referral agents, and providers. The authors urge psychiatry to help in removing these obstacles.
Endothelial deletion of protein tyrosine phosphatase-1B protects against pressure overload-induced heart failure in mice
Authors: Rajinikanth Gogiraju, Marco R. Schroeter, Magdalena L. Bochenek, Astrid Hubert, Thomas Münzel, Gerd Hasenfuss, Katrin Schäfer
Journal: Cardiovascular Research (2016)

Cardiac angiogenesis is an important determinant of heart failure. We examined the hypothesis that protein tyrosine phosphatase (PTP)-1B, a negative regulator of vascular endothelial growth factor (VEGF) receptor-2 activation, is causally involved in the cardiac microvasculature rarefaction during hypertrophy and that deletion of PTP1B in endothelial cells prevents the development of heart failure. Cardiac hypertrophy was induced by transverse aortic constriction (TAC) in mice with endothelial-specific deletion of PTP1B (End.PTP1B-KO) and controls (End.PTP1B-WT). Survival up to 20 weeks after TAC was significantly improved in mice lacking endothelial PTP1B. Serial echocardiography revealed a better systolic pump function, less pronounced cardiac hypertrophy, and left ventricular dilation compared with End.PTP1B-WT controls. Histologically, banded hearts from End.PTP1B-KO mice exhibited increased numbers of PCNA-positive, proliferating endothelial cells resulting in preserved cardiac capillary density and improved perfusion as well as reduced hypoxia, apoptotic cell death, and fibrosis. Increased relative VEGFR2 and ERK1/2 phosphorylation and greater eNOS expression were present in the hearts of End.PTP1B-KO mice. The absence of PTP1B in endothelial cells also promoted neovascularization following peripheral ischaemia, and bone marrow transplantation excluded a major contribution of Tie2-positive haematopoietic cells to the improved angiogenesis in End.PTP1B-KO mice. Increased expression of caveolin-1 as well as reduced NADPH oxidase-4 expression, ROS generation and TGFβ signalling were observed and may have mediated the cardioprotective effects of endothelial PTP1B deletion. Endothelial PTP1B deletion improves cardiac VEGF signalling and angiogenesis and protects against chronic afterload-induced heart failure. PTP1B may represent a useful target to preserve cardiac function during hypertrophy.
Predicting Protein Subcellular Localization: Past, Present, and Future
Authors: Pierre Dönnes, Annette Höglund
Journal: Genomics Proteomics & Bioinformatics (2004)

Abstract Functional characterization of every single protein is a major challenge of the post-genomic era. The large-scale analysis of a cell’s proteins, proteomics, seeks to provide these proteins with reliable annotations regarding their interaction partners and functions in the cellular machinery. An important step on this way is to determine the subcellular localization of each protein. Eukaryotic cells are divided into subcellular compartments, or organelles. Transport across the membrane into the organelles is a highly regulated and complex cellular process. Predicting the subcellular localization by computational means has been an area of vivid activity during recent years. The publicly available prediction methods differ mainly in four aspects: the underlying biological motivation, the computational method used, localization coverage, and reliability, which are of importance to the user. This review provides a short description of the main events in the protein sorting process and an overview of the most commonly used methods in this field.
Treatment of alcoholism among schizophrenic outpatients: 4-year outcomes
Authors: R E Drake, G J McHugo, D L Noordsy
Journal: American Journal of Psychiatry (1993)

In this pilot study, the authors assessed 4-year outcomes for 18 schizophrenic outpatients with alcoholism who were treated in an innovative dual-diagnosis program. Over half (61.1%) achieved stable remissions from alcoholism. The mean duration of remission was 26.5 months.
Carers need financial assistance to buy help
Authors: F. Eskin
Journal: BMJ (1996)

Insurers, doctors, and patients do not need to be apologetic about private treatment EDITOR,-The private sector facilities that David Currie describes in his area bear no resemblance to those of the clinics in which I work.'The days when private treatment was restricted to minor surgery in "dubious nursing homes" are long past, and the private sector, at least in the south east of Britain, has expanded to cover almost every medical and surgical contingency.In some private clinics facilities are now provided that match and sometimes surpass those in the best NHS units.Of course there are good and bad units-and probably good and bad doctors-in both public and private sectors, and so, unlike Currie, I find it entirely understandable that some people wish to choose for themselves what they consider to be the best available care.Although most doctors in Britain are committed to the NHS, many can appreciate the advan- tages of having a private sector in parallel with public facilities.I do not believe that the medical insurers, doctors, or, indeed, patients need be in the least bit apologetic about choosing to operate or be treated outside the NHS.With the advent of audit and accreditation it will not be long before private practice can be conducted only in properly accredited units, and I find it interesting that most hospitals already accredited by the King's Fund are in the independent sector.Currie's article, in which he refers to his "brooding", "resentment," "enragement," and "spiteful satisfaction," amply testifies to his bigoted perspective; fortunately, both readers and the general public have the freedom to choose whether to be influenced by him.Most, when inquiring about the benefits of private health care, will seek accurate and unbiased information before committing themselves to an opinion, a decision, or, indeed, a subscription.
Brewster v Dukakis: developing community services through use of a consent decree
Authors: R L Okin
Journal: American Journal of Psychiatry (1984)

Filed against the state of Massachusetts in 1977, Brewster v Dukakis involved the claim that psychiatric patients living in state hospitals or at risk of being hospitalized in these facilities have a right to treatment in community settings. The decree that emanated from the suit resulted over a 5-year period in a tenfold increase in state expenditures for community mental health services, a 48% decline in the state hospital census, and a 15% drop in the state hospital admission rate in the region of the state targeted by the suit. Factors that facilitated this outcome are described, as well as the dangers and limitations of exclusive reliance on the judicial process to promote the development of community services.
Abstract P6-10-02: Patient rather than physician-related barriers to tamoxifen uptake for breast cancer prevention in high-risk women
Authors: AR Skandarajah, S Thomas, L Chin-Lenn, B Mann, G Lindeman
Journal: Cancer Research (2016)

Abstract Background: Tamoxifen use for 5 years confers 35% risk reduction in breast cancer at 15 years, although the evidence to support its use for BRCA1 or BRCA2 mutation carriers is less clear. Since 2014, it has been our policy to discuss and recommend endocrine prevention to every eligible individual who attends the risk management clinic (for gene carriers or women with a strong family history) at our institution. Aim: To assess the uptake of endocrine prevention in a high risk population when uniformly recommended and reasons for declining prevention. Methods: All patients attending risk management clinic between February 2014 until May, 2015 received both verbal and written evidence-based information on endocrine prevention and were registered prospectively. Endocrine prevention use and cessation was captured. Reasons for declining or ineligibility for tamoxifen use were recorded. Results: During the study period, 314 consultations were carried out on 248 women. They comprised 38 BRCA1 and 42 BRCA2 mutation carriers, 4 Peutz-Jegher syndrome patients, 155 women with strong family history, 9 with moderate family history. Their median age was 39.7 (range: 21-70 years). Despite routine policy, Tamoxifen prevention was routinely discussed, except where a patient required biopsy or was given biopsy results n=14 (7%). One patient had a new cancer diagnosis during this period. In 52 women, tamoxifen was not recommended for the following reasons: patients re-assessed as moderate risk (9), on other prevention trials (2), very young/old age (28), pregnant or breast-feeding (10) and previous mastectomy/cancer/DCIS (3). Of the remaining 182 eligible patients, 14 (8%) were on tamoxifen (median duration 12 months, range= 1-20 months), 8 (4%) had ceased tamoxifen due to side effects. Main reasons for declining were 25 (14%) were trying to conceive, 34 (19%) prefer prophylactic mastectomy, 15 (8%) were concerned regarding the side effects, 5 (3%) were currently suffering from menopause and 4 (2%) wished to await salpingo-oophorectomy. 66 (36%) indicated that they were ‘not interested’. Conclusions: Physician-reluctance is not the reason for poor uptake of endocrine prevention in a specialized risk management clinic. Contraindications are common, many women elect for alternative risk reducing strategies and despite supportive evidence, many women prefer to choose surveillance alone over medical prevention. Citation Format: Skandarajah AR, Thomas S, Chin-Lenn L, Mann B, Lindeman G. Patient rather than physician-related barriers to tamoxifen uptake for breast cancer prevention in high-risk women. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-10-02.
Association Of Chemokine Receptor CCR5, CCR6 and CCR7 Expressions On T Lymphocyte Subsets In Recipients After Allo-HSCT With Acute GvHD
Authors: Meng Wang, Han-Yun Ren, Yu-Jun Dong, Ze-Yin Liang, Zhi-Xiang Qiu, Wei Liu, Li-Hong Wang
Journal: Blood (2013)
Lasers in Medicine and Surgery
Authors: J S McCaughan, C Mackety
Journal: JAMA (1986)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
A phase Ib study of investigational pan-RAF kinase inhibitor MLN2480 plus investigational TORC1/2 inhibitor MLN0128, investigational Aurora A kinase inhibitor alisertib (MLN8237), or paclitaxel in patients (pts) with advanced solid tumors.
Authors: Anthony J. Olszanski, Mark R. Middleton, Rastilav Bahleda, Rebecca Suk Heist, Lakshmi Rangachari, Xiaofei Zhou, Viviana Bozón, Michelle Kneissl, Teresa Macarulla
Journal: Journal of Clinical Oncology (2015)

TPS2609 Background: Signaling hyperactivation secondary to MAPK pathway aberrations are common. RAF kinases play key roles in the RAS/RAF/MEK/ERK signaling cascade, representing potentially valid therapeutic targets. In a phase 1 study, single-agent MLN2480 had an acceptable safety profile, expected pharmacodynamic effects and preliminary antitumor activity (Middleton et al, ENA 2014, Abstract 364). Preclinically, MLN2480 has shown synergistic/additive effects in xenograft models and cell lines when combined with MLN0128, alisertib or the taxane, docetaxel. Potential overlapping toxicities of each combination are expected to be manageable, with no apparent risks for clinically meaningful pharmacokinetic (PK) drug–drug interactions based on in vitro ADME data and exposures achieved clinically. Methods: This three-arm, open-label study (NCT02327169) is the first-in-human study for MLN2480 + MLN0128/alisertib/paclitaxel. Primary objective is to evaluate the safety, tolerability, and MTD of each combination. Secondary objectives are to characterize PK profiles and preliminary antitumor activity. An exploratory objective is to assess tumor samples and circulating tumor DNA for biomarkers of response/resistance. Pts aged ≥ 18 yrs with radiographically/clinically evaluable advanced solid tumors who failed standard therapies are eligible. Pts in the expansion phase require tumors measurable by RECIST v1.1. MAPK pathway aberrations are not required. Pts will receive MLN2480 100–200 mg (d 1, 3, 5 per week) in 28-d cycles plus: (A) MLN0128 2–9 mg (d 2, 3, 4 per week), (B) alisertib 30–50 mg twice daily (d 1–3, 8–10, 15–17) or (C) paclitaxel 80 mg/m2 (d 1, 8, 15) for up to 12 cycles. Serial blood samples will be taken in cycle 1 for PK evaluation. A 3+3 dose escalation algorithm, based on cycle 1 DLTs, will be used, with up to 20/20/15 pts in groups A/B/C. Enrollment is ongoing. Once MTDs are established, ≥ 1 combination regimens will be selected for the expansion phase (~16 pts per group) based on safety, exposure and preliminary antitumor activity data. Clinical trial information: NCT02327169.
Mutations of Genes Linked to Epigenetic Regulation Are Frequently Gained in Relapsed Cytogenetically Normal Acute Myeloid Leukemia
Authors: Luise Hartmann, Sebastian Vosberg, Klaus H. Metzeler, Daniela Schumacher, Friederike Pastore, Kathrin Bräundl, Evelyn Zellmeier, Bianka Ksienzyk, Nikola P Konstandin, Stephanie Schneider, Stefan Krebs, Alexander Graf, Helmut Blum, Martin Neumann, Claudia D Baldus, Stefan K. Bohlander, Wolfgang Hiddemann, Karsten Spiekermann, Philipp A. Greif
Journal: Blood (2015)
Molecular Mechanisms of Type II Factor XIII Deficiency: Novel Gly562-Arg Mutation and C-Terminal Truncation of the A Subunit Cause Factor XIII Deficiency as Characterized in a Mammalian Expression System
Authors: Nobumasa Takahashi, Hiroaki Tsukamoto, Hideaki Umeyama, Giancarlo Castaman, Francesco Rodeghiero, Akitada Ichinose
Journal: Blood (1998)
Classification of Colorectal Polyps: Guidelines for the Endoscopist
Authors: C. Rubio, E. Jaramillo, A. Lindblom, F. Fogt
Journal: Endoscopy (2002)

Polyp is a Greek word used to denote a protruding excrescence linked to a mucous membrane by a pedicle. Today we know that the pedicle evolves as a result of peristaltic activity which projects forward a protruding polyp of substantial size growing on loose submucosal tissue. On the basis of clinical data, colorectal polyps are classified as sporadic or hereditary. Sporadic colorectal polyps evolve after environmental insults of long duration. Consequently they are age-related and often seen in older patients. Polyps generated as a result of a genetic predisposition, are often found in younger patients.
Letter to the Editor
Authors: P Pagliaro
Journal: Cardiovascular Research (1999)

Dear Editorand any increase in pressure is prevented by connecting the two femoral arteries with a blood reservoir.Our results I read the nicely written and interesting review by Kojda also indicate that the sympathetic discharge is not affected and Kotteberg [1].I found very interesting the section by the NO-inhibition ''per se'', but, before and after devoted to the chronotropic effects of NO.I agree with the NO-inhibition, it can be reduced to the same extent by the conclusions of the authors that NO has a positive chrono-same increase in pressure.In their paper Ward and Angus tropic effect which has been described and explained.[5], reported that in the rabbit NO-inhibition induces a However, I must note that the in vivo set-up in animals of reduction in heart rate in spite of pharmacological bloc-Krege et al. [2], and of Kojda et al. [3], quoted in this kade of the autonomic reflexes.review with the numbers 98 and 99 of the references, are not the most appropriate to claim a negative chronotropic effect for the NO inhibition in vivo.These two papers [2,3]
Studies of Heterografts in Diffusion Chambers in Mice2
Authors: Glenn H. Algire, Mary L. Borders, Virginia J. Evans
Journal: JNCI Journal of the National Cancer Institute (1958)

Journal Article Studies of Heterografts in Diffusion Chambers in Mice Get access Glenn H. Algire, Glenn H. Algire Search for other works by this author on: Oxford Academic PubMed Google Scholar Mary L. Borders, Mary L. Borders Search for other works by this author on: Oxford Academic PubMed Google Scholar Virginia J. Evans Virginia J. Evans Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 20, Issue 6, June 1958, Pages 1187–1201, https://doi.org/10.1093/jnci/20.6.1187 Published: 01 June 1958 Article history Received: 10 December 1957 Published: 01 June 1958