tbuckley/cabot-search huggingface dataset:
Enhanced IgG Hexamerization Mediates Efficient C1q Docking and Complement-Dependent Cytotoxicity; Preclinical Proof Of Concept On Primary CLL and Burkitt Lymphoma
Authors: Frank J Beurskens, Rob N de Jong, Sandra Verploegen, Marleen Voorhorst, Kristin Strumane, Margaret A. Lindorfer, Ronald P. Taylor, Erica Ollmann Saphire, Dennis Burton, Janine Schuurman, Paul W.H.I. Parren
Journal: Blood (2013)
A phase I pharmacokinetic trial of sonic hedgehog (SHH) antagonist GDC-0449 in pediatric patients with recurrent or refractory medulloblastoma: A Pediatric Brain Tumor Consortium study (PBTC 25).
Authors: A. J. Gajjar, C. F. Stewart, D. W. Ellison, T. Curran, P. Phillips, S. Goldman, R. Packer, L. E. Kun, J. M. Boyett, R. J. Gilbertson
Journal: Journal of Clinical Oncology (2010)

CRA9501 Background:Aberrant signaling in SHH pathway is implicated in causing medulloblastoma in approximately 20% of children with this disease. GDC-0449 is an orally active agent that binds to the SMO receptor and prevents downstream signaling through GLI. Preclinical murine models predict efficacy of an SMO antagonist to treat tumors dependent on the SHH pathway. Adult studies have documented the efficacy of this compound against recurrent medulloblastoma and basal cell carcinoma. A phase I pharmacokinetic trial of GDC 0449 was conducted in children with recurrent or refractory medulloblastoma to select, based on safety and pharmacokinetics, one of two dosages to recommend for a pediatric phase II trial. We also used immunonistochemistry (IHC) and in situ hybridization (ISH) on paraffin-embedded tissue to determine which tumors belonged to the SHH subtype. Methods: GDC 0449 was administered once daily for 28 days dose levels of (1) 85 mg/m 2 /dose and (2) 170 mg/m 2 /dose. A course was defined as 28 days in duration. PK analysis was performed during the first course and steady-state concentrations were obtained prior to each subsequent course (day 21). MRI scans of the knees were obtained at baseline and 3 mos to assess abnormalities in bone development. Results: To date 11 eligible patients have been enrolled on the trial (10 males, median age 11.6 years (range 4.4–20.9). All patients were fully evaluable for toxicity. 1 DLT, grade 3 gamma-Glutamyl transpeptidase, occurred in a patient enrolled at 170 mg/m 2 /dose. There were no grade 4 toxicities. The median (range) steady-state day 21 concentration at 85 mg/m 2 (n=5) is 10.15 μ M (9.10–18.99 μ M) and at 170 mg/m 2 (n=2) is 14.50 μ M (14.43–14.57 μ M). The steady-state GDC-0449 clearance (n=7) is 0.86 (0.44 – 1.17 L/h/m 2 ). At steady state (day 21), the ratio of GDC-0449 CSF to plasma is 1.3%, which is an estimate of the CSF penetration of GDC-0449. Conclusions: GDC 0449 is well-tolerated in children with recurrent or refractory medulloblastoma. The phase I study estimating the recommended phase II dose of GDC 0449 is ongoing; final results including medulloblastoma subgroup data will be presented. [Table: see text]
In vivo and ex vivo proofs of concept that cetuximab conjugated vitamin E TPGS micelles increases efficacy of delivered docetaxel against triple negative breast cancer
Authors: Rajaletchumy Veloo Kutty, Sing Ling Chia, Magdiel I. Setyawati, Madaswamy S. Muthu, Si-Shen Feng, David Tai Leong
Journal: Biomaterials (2015)
Abstract 3485: A Japanese Diet and 19-Year Mortality: NIPPON DATA80.
Authors: Yasuyuki Nakamura, Hirotsugu Ueshima, Takehito Hayakawa, Yoshikuni Kita, Robert D Abbott, Akira Okayama
Journal: Circulation (2007)

Objectives: Although dietary patterns are associated with death from several causes, few studies have examined the association between Japanese diet and mortality outcomes. Methods: We analyzed the...
Abstract 5552: Bioactive Gas/Drug Co-encapsulation and Release Improve Attenuation of Intimal Hyperplasmia Following Acute Arterial Injury
Authors: Melanie R Moody, Shaoling Huang, Hyunggun Kim, Stephen Chrzanowski, David D McPherson
Journal: Circulation (2008)

Introduction: Evidence suggests that vascular smooth muscle cell proliferation, clot formation and inflammation play important roles in early vascular injury following intervention. A strategy with pleiotropic actions is more likely to be effective in limiting neointimal proliferation. Echogenic liposomes (ELIP) have the ability to encapsulate both bioactive gases (nitric oxide -NO) and pharmaceutics allowing attenuation of intimal hyperplasia following vascular injury.  Methods: Cationic liposomes containing nitric oxide (NO) and rosiglitazone were prepared by hydration, sonication and freeze-thawing. Pressurization of the lipid dispersion with NO/argon after sonication permits co-encapsulation of NO into the rosiglitazone-loaded ELIP. Acute arterial injury was created in rabbits using balloon injury to the common carotid artery. NO and rosiglitazone loaded ELIP were administered intraarterially into the common carotid artery. Fourteen days later the carotid arteries were removed for histologic examination.  Results: The technique resulted in 100 μg rosiglitazone and 10 μl NO/argon co-encapsulated into 1 mg of liposomes. The liposomes were rendered echogenic allowing ultrasound imaging of ELIP delivery and distribution. The combined NO-rosiglitazone delivery provided greater attenuation of intimal proliferation when compared to NO or rosiglitazone delivery alone (88±15% vs. 75±13% or 51±6%).  Conclusion: This novel methodology has the ability to direct two quite different agents to limit neointimal proliferation at the time acute intervention.
Abstract 15276: Echocardiographic Features Defining Right Ventricle Dominant Unbalanced Atrioventricular Septal Defect: a Multi-institutional Congenital Heart Surgeons' Society Study
Authors: Meryl S Cohen, Anusha Jegatheeswaran, Brian W McCrindle, Jeanne M Baffa, David B Gremmels, Christopher Caldarone, William G Williams, David M Overman, Luc L Mertens
Journal: Circulation (2011)

Objectives: Right ventricle (RV) dominant unbalanced atrioventricular septal defect (AVSD) remains challenging with regard to definition and management. We sought to assess which echo features best characterized patients based on functional and anatomic features.

Methods: From a cohort of AVSD patients at 4 CHSS institutions (2000-2006), diagnostic echos of 60 randomly selected balanced patients and all 52 RV dominant patients (based on atrioventricular valve (AVV) index) underwent detailed review. Cluster analysis of these variables was used to group patients with similar features based on the echo data. Discriminant function analysis was used to determine which variables differentiated these groups.

Results: Three groups were identified from the cluster analysis. Discriminant function analysis found that the echo variables that differentiated these groups were the RV:left ventricle (LV) inflow angle (RV/LVinflow), LV width/LV length, left AVV color diameter at smallest inflow, left AVV color diameter at annulus, right AVV overriding left atrium, and LV width. Outcomes associated with the 3 groups indicated that one group (1) represented balanced patients, while two groups (2,3) with similar outcomes represented unbalanced patients (Table). The dominant differentiating variable was RV/LVinflow (partial R2=0.86) (Figure), which we defined as the angle between the base of the RV and LV free wall, using the top of the ventricular septum as apex of the angle.

Conclusions: The angle of RV/LVinflow is an important defining echo measure of RV dominance in patients with right unbalanced AVSD. The utility of this measure needs to be confirmed with a prospective study.

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Phase I-II Study of Sequential Therapy with Decitabine Followed By Clofarabine, Idarubicin, and Cytarabine (DAC-CIA regimen) in Relapsed/Refractory Acute Myeloid Leukemia (AML)
Authors: Nitin Jain, Farhad Ravandi, Guillermo Garcia-Manero, Gautam Borthakur, Tapan Kadia, Elias Jabbour, Naveen Pemmaraju, Naval Daver, Courtney D. DiNardo, Marina Konopleva, Allison Pike, Carol Bivins, Sherry Pierce, Susan O'Brien, Jorge E. Cortes, Hagop M. Kantarjian
Journal: Blood (2014)
The initial contract in the treatment of borderline patients
Authors: Michael A. Selzer, Harold W. Koenigsberg, Otto F. Kernberg
Journal: American Journal of Psychiatry (1987)

The initial treatment contract with a borderline patient recognizes the patient's potential for destructiveness and builds in safeguards. The therapist's effort to protect the treatment mobilizes the patient's primitive defenses. The therapist must be prepared to respond to resistance to the contract by clarification, confrontation, and occasionally interpretation. Although countertransference reactions evoked by the patient's use of primitive defenses complicate the therapist's task of defining the necessary treatment frame, the therapist's recognition of countertransference responses can enable him to establish and enforce an appropriate contract.
Informed consent may increase non-attendance rate
Authors: M Baum
Journal: BMJ (1995)

EDITOR,—The Health of the nation aims at reducing deaths from breast cancer in women invited for screening by a quarter by 2000. This target is unlikely to be met as there are only five years to go; judging by the current rates of interval breast cancer, we are probably only half way to that target.1 If there is any reduction in mortality from breast cancer by 2000 it is just as likely to be attributable to the improvements in treatment since the …
Abstract 4357: Soluble ST-2 Concentrations to Predict Sudden Cardiac Death in Stable Heart Failure Patients
Authors: Antoni Bayes-Genis, Domingo Pascual-Figal, Rafael Vazquez-Garcia, Rosa Bonet-Marques, Teresa Puig-Domingo, Joan Cinca-Coscollola, Antoni Bayes de Luna, James V Snider, Jordi Ordonez-Llanos
Journal: Circulation (2008)

Background &amp; Aim: The soluble form of the ST2 receptor (sST2) is released, like B-natriopeptides, by cardiomyocytes in response to mechanical overload. sST2 has been shown useful for predicting short- and long-term risk in heart failure (HF). Sudden cardiac death (SCD) is a poorly predictable HF-complication; we previously showed that NT-proBNP and left atrial size (LA) were prognostic of SCD in a cohort of stable HF patients. Since NT-proBNP and sST2 share some common features, we evaluated the role of sST2 to predict SCD in HF. Patients &amp; Methods: A 1:2 case:control design was used. Ninety-nine stable HF patients were included and followed during 3 years (942±323 days); 36 suffered SCD (Cases) and 63 survived (Controls). Cases and Controls were matched by age (66±11 years), sex (83% male) and LVEF (mean: 29%). NT-proBNP and sST2 were measured by immunoassays in serum/ plasma samples collected at inclusion; clinical information was recorded at inclusion and during follow-up. Results: Cases had more often prior history of ischemic disease (72 vs 44%) and AMI (64 vs 41%), lower eGFR (54 vs 64 mL/min) and higher NYHA class (50 vs 22% in class III), LA (27 vs 23 mm/m 2 ) and NT-proBNP (2873 vs 966 ng/L) than Controls (all variables, p&lt;0.05). sST2 was higher in Cases (0.232 vs 0.121 ng/L, p=0.002) and unrelated to eGFR. ROC analysis of sST2 and NT-proBNP showed optimal cut-points to predict SCD of 0.152 and 2005 ng/L, respectively. sST2 values &gt; 0.152 ng/L were found in 78% of Cases and 44% of Controls (p&lt;0.001). In multivariable analysis sST2, NT-proBNP, eGFR and LA were independent predictors of SCD. When sST2 and NT-proBNP concentrations (dichotomized by the set cut-points) were analyzed combined as a single variable the OR to predict SCD raised to 21.857 (95% CI: 2.655–179.909, p=0.004). eGFR and indexed LA size were weaker predictors of SCD (OR: 1.665 and 1.157, respectively). The area under ROC of the combined variable to predict SCD was 0.869 (95% CI: 0.798 – 0.940). Conclusions: sST2 is a novel biomarker for SCD prediction in stable HF patients. A multimarker approach using sST2 and NT-proBNP improves the identification of HF patients at high risk of SCD.
Caring for Lesbian and Gay People: A Clinical Guide
Authors: K. Oriel
Journal: JAMA (2004)

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
Making self regulation credible
Authors: J. Johnson
Journal: BMJ (1998)

Professional self regulation has so far been vested in the General Medical Council, which has done much recently to modernise its way of working. The new performance procedures go a long way to plug a major gap in its ability to deal with cases which, though serious, may not be best dealt with by erasure or suspension from the medical register. Each problem dealt with by the GMC, however, represents an issue which has not been adequately addressed locally, and it is locally that major changes are needed if self regulation is to be credible.

Firstly, outcome data for individual treatments are needed to allow doctors to compare their own results with those of colleagues throughout the NHS performing the same procedures. Such benchmarking has been found useful in cardiothoracic surgery 1 2 and lends itself to specialties which produce definite and measurable outcomes and complications but could in principle be adapted to all specialties. Individual doctors' results need to be corrected for case difficulty and comorbidity—which is difficult.

For cardiothoracic surgery Keogh et al have described some of the problems of risk stratification, including the necessity for good data collection.3 …
Trial of Oxyphenbutazone for Postoperative Edema After Bilateral Herniorrhaphy
Authors: J D ILES
Journal: JAMA (1963)

A double-blind controlled trial was carried out to test the value of oxyphenbutazone (Tandearil; Geigy Pharmaceuticals) in preventing the troublesome edema of external genitalia that may occasionally develop after bilateral inguinal herniorrhaphy. Oxyphenbutazone, 200 mg., or a placebo identical in appearance, was given orally to each of 133 patients the day before their first operation and 300 mg. was administered on each subsequent day until discharge. The second operation was performed 48 hours after the first, and each patient was discharged 72 hours thereafter, at which time his edema was assessed. Strictly double-blind conditions governed distribution of tablets and assessment of edema. Sixty-eight patients received oxyphenbutazone and 65 the placebo. The degrees of edema observed in both groups were approximately the same. It is possible that mechanical factors associated with herniorrhaphy may help to produce edema, in addition to the ordinary tissue response to injury. No toxic reactions to oxyphenbutazone were observed.
Psychosocial Variables and the Course of Cancer
Authors: Donna P. Funch, Neil A. Fiore, Peter P. Vitaliano, Patricia A. Lipscomb, John E. Carr, Sandra M. Levy, Alan Winkelstein, Bruce S. Rabin, Marc Lippman, Sheldon Cohen, Barrie R. Cassileth, David S. Miller, Clifford Miller, Edward J. Lusk, Lorraine Brown
Journal: New England Journal of Medicine (1985)
Single nucleotide polymorphism in MDM2 is associated with sporadic endometrial cancer risk.
Authors: Christine S. Walsh, H. Phillip Koeffler, Beth Y. Karlan
Journal: Cancer Research (2006)

5400   Objectives: MDM2 is an important negative regulator of the p53 tumor suppressor protein. A naturally occurring T/G single nucleotide polymorphism (SNP) in the MDM2 gene promoter, SNP309, causes an increase in MDM2 protein levels and impairment of p53 tumor suppressor activity. SNP309 occurs at a relatively high frequency in the general population (40% heterozygous T/G, 10% homozygous G/G) and has been associated with accelerated tumorigenesis in hereditary Li-Fraumeni associated cancers as well as in sporadic soft tissue sarcomas. The objective of this study was to examine the association between SNP309 and sporadic endometrial cancer risk. Methods: Genomic DNA was isolated from 73 patients with endometrial cancer and 79 unaffected controls. The MDM2 gene promoter region was amplified by PCR and the SNP309 genotype determined by restriction enzyme digestion of the amplified DNA fragment. Logistic regression analysis was used to determine the relationship between genotypes and endometrial cancer features. Results: The homozygous G/G genotype was found in 25% of endometrial cancer cases and 11% of controls. In an age-adjusted analysis of cases and controls, the G/G genotype increased the risk of endometrial cancer 2.76-fold (95% CI 1.06, 7.20; p=0.037) compared to presence of a wild-type T allele (T/G and T/T genotypes). No association was found between the SNP309 G/G genotype and endometrial cancer histology (OR 0.85, 95% CI 0.16, 4.55), grade (OR 0.98, 95% CI 0.58, 1.64), stage (OR 0.85, 95% CI 0.51, 1.44), or age of diagnosis (p=0.32). Conclusions: The MDM2 SNP309 homozygous G/G phenotype may be a genetic variant that influences sporadic endometrial cancer susceptibility.
Abstract 16329: Ten Novel Mutations of the TAZ Gene in Patients With Barth Syndrome
Authors: Hu Wang, Brandy A Westerfield, Liana S Pena, Andy Do, Gilma A Rodriguez, Wenxin Zou, Daniel J Penny, Yuxin Fan
Journal: Circulation (2011)

Introduction Barth Syndrome (BTHS) is an X-linked recessive multisystem disorder conventionally characterized by dilated cardiomyopathy (DCM) with endocardial fibroelastosis (EFE), skeletal myopath...
Abstract 17762: Nucleosome Assembly Protein 1-like 1 Knockdown Promotes Cardiomyocytes Differentiation by Mesoderm Induction Through Notch Signaling in Mouse Induced Pluripotent Stem Cells
Authors: Hui Gong, Yuan Yan, Yuanyuan Xue, Peipei Yin, Zhiwen Ding, Guoping Zhang, Chunjie Yang, Junbo Ge, Yunzeng Zou
Journal: Circulation (2013)

Although induced pluripotent stem cells (iPSCs)-derived cardiomyocytes are expected as the potential source of cell-based therapy for heart diseases, the rate of derivation is too low for clinical ...
Abstract #LB-245: Anthocyanins from black raspberries modulate genes involved in Wnt signaling, inflammation, cell cycle, and angiogenesis in human colon cancer cells
Authors: Bethany Larue, Claire Seguin, Claudio Rocha, Gary Stoner, Li-Shu Wang
Journal: Cancer Research (2009)

We reported that the short-term (2-to-4 wk) treatment of colorectal cancer patients with freeze-dried black raspberries (BRBs) positively modulated biomarkers of cell proliferation, apoptosis, angiogenesis, and components of the Wnt pathway in colorectal tumor specimens. The present study was conducted to identify additional biomarkers of BRB effects on colon cancer cells. HCT 116 human colon cancer cells were treated with an anthocyanin-rich fraction from BRBs at 5 µg/ml every day for three days. The effects of the berries on gene expression were analyzed using PCR mini-microarrays, targeting 588 cancer-related genes including genes associated with Wnt signaling, angiogenesis, inflammation, apoptosis, cell-cell and cell-matrix adhesion and cell cycle. The results showed that 50 of the 588 genes expressed \#8805; 2.5 fold up/down regulation in anthocyanin-treated vs. non-treated cells; 34 of the 50 genes (68%) were positively modulated. Interestingly, Wnt signaling genes comprised 6 of the 34 genes, and all 6 ( WNT7B, WNT10A, WNT16, FZD2, LRP6,  and  DVL1 ) were positively down-regulated by anthocyanin treatment. Inflammatory cytokines and their receptors comprised 13 of the 34 genes and these were positively modulated (i.e.,  IL1F9 ,  IL10RA , and  CCR9  all down-regulated), as were genes associated with angiogenesis (i.e.,  HGF ,  ID3 , and  CDH5  all down-regulated) and cell cycle control (i.e.,  ABL1, CCNT2 , and  GTSE1  all down-regulated). Notably, three genes were markedly down-regulated by berry anthocyanins; i.e.,  WNT7B  by 53-fold,  DVL1  by 39-fold, and  ABL1  by 28-fold. These changes in gene expression were validated using Real-time PCR. This study is the first to show that anthocyanins from BRBs modulate genes upstream of the Wnt pathway. It may have also identified additional biomarker genes that will be further investigated in human colon tumor specimens from berry-treated patients. Supported by NCI grant CA103180 and USDA grant 38903-03560.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr LB-245.
Abstract 17276: Cyclophilin D is Required for Mitophagy-Regulating Parkin Translocation to Mitochondria
Authors: Giovanni Quarato, Chengqun Huang, Roberta A Gottlieb
Journal: Circulation (2011)

INTRODUCTION Cyclophilin D (CyD), encoded by the Ppif gene, is a mitochondrial protein that regulates the Mitochondria Permeability Transition Pore (MPTP) and is necessary for the removal of damaged mitochondria via autophagy in cardiac cells. Ppif -/- mice show an increase in the mitochondrial calcium retention capacity and a desensitization of MPTP opening. These features are associated with protection against ischemia/reperfusion injury. However recent finding show that CyD is involved in different physiological pathways important for cell homeostasis. HYPOTHESIS We tested the hypothesis that the CyD mediates mitochondrial removal by controlling Parkin translocation to the mitochondrial outer membrane. METHODS Cardiac mitochondria were isolated from wild type and Ppif -/- young (2 months) and old (20 months) mice according to standard protocol using a sucrose based buffer. RESULTS Western Blot analysis of total heart tissue lysate showed a 1.8 fold increase in the microtubule-associated protein1 light chain 3 (LC3) and a 2.2 fold increase in the total Parkin protein levels in the Ppif -/- young mice compared to age matched wild type mice. Parkin in the mitochondrial fraction was 2.0 fold less in the samples from young and old Ppif -/- mice compared to age-matched wild type mice. The diminished activity in the Parkin-dependent mitophagy results in accumulation of defective mitochondria, leading to metabolic reprogramming followed by pathological hypertrophy. While young Ppif -/- mice show normal phenotype, old mice develop cardiac hypertrophy with elevated HW/BW ratio and ANF compared to age-matched wild type mice. CONCLUSIONS The decrease in the Parkin-dependent mitophagy machinery activity observed in the Ppif -/- mice describe for the first time the requirement for CyD in the Parkin-dependent mitophagy and give a further explanation for the cardiac hypertrophic phenotype in old Ppif -/- mice.