tbuckley/cabot-search huggingface dataset:
Abstract 3724: Wogonin enhances tumor necrosis factor-related apoptosis-inducing ligand's antitumor activity in vivo through H2O2-mediated downregulation of X-linked inhibitor of apoptosis protein and cellular inhibitor of apoptosis protein 1 and 2
Authors: Lan Yang, Xuelian Zheng, Yong Lin, Xia Wang
Journal: Cancer Research (2012)

Abstract Numerous malignant cells are resistant to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced cytotoxicity, limiting value of TRAIL as an antitumor therapeutics. Combination of TRAIL with other agents is a promising strategy to overcome TRAIL resistance. Wogonin (5, 7-dihydroxy-8-methoxyflavone), a flavonoid originated from the root of the medicinal herb Scutellaria baicalensis Georgi, has been shown to enhance TRAIL-induced apoptosis in malignant cells in in vitro studies. However, whether wogonin enhances TRAIL's antitumor activity in vivo has never been studied. In this study, we first found that wogonin sensitized a variety of cancer cells including A549, HeLa and SKOV3 to TRAIL-induced apoptosis, as indicated by increased annexin V staining and enhanced activation of caspase-8 and -3 in TRAIL and wogonin cotreated cells, whereas having marginal effect on non-transformed bronchial epithelial cells and cervical epithelial cells. Then the effect of combination of TRAIL and wogonin was tested in a xenografted tumor model with A549 cells in nude mice. The results show that wogonin greatly enhanced TRAIL-induced suppression of tumor growth, which was accompanied with increased apoptosis in tumor tissues determined by a terminal deoxynucleotidyl-transferase -mediated dUTP nick-end labeling (TUNEL) assay. The protein levels of X-linked inhibitor of apoptosis protein (XIAP) and cellular inhibitor of apoptosis protein 1 and 2 (cIAP-1 and cIAP-2) were markedly reduced in both cultured cells and xenografted tumor tissues with co-treatment of wogonin and TRAIL. The down-regulation of these antiapoptotic proteins was likely mediated through proteasomal degradation and involved intracellular H2O2, as wogonin robustly induced H2O2 accumulation in A549 cells and the reactive oxygen species scavengers butylated hydroxyanisole (BHA) and N-acetyl-L-cysteine (NAC) and the proteasome inhibitor MG132 restored the expression of these antiapoptotic proteins and suppressed cytotoxicity in cells co-treated with wogonin and TRAIL. These results provide important in vivo evidence supporting the application of wogonin as TRAIL sensitizer for cancer therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3724. doi:1538-7445.AM2012-3724
18F-FDG PET/CT in a Recurrent Diffuse Malignant Peritoneal Mesothelioma
Authors: Qi Cao, Minh Lu, Jonathon Heath, Petr F. Hausner, H. Richard Alexander, Vasken Dilsizian, Wengen Chen
Journal: Clinical Nuclear Medicine (2012)

Peritoneal mesothelioma is a rare and aggressive tumor. Early diagnosis of the disease is difficult, delaying effective treatment. We report a case of recurrent, biphasic, diffuse, malignant peritoneal mesothelioma. Initial abdominal computed tomography showed abnormal but nonspecific findings suggestive of an ovarian malignancy, with a negative endoscopy and laboratory studies. An abdominal exploratory laparotomy found widespread malignancy within the peritoneum with a pathological diagnosis of peritoneal mesothelioma. A PET/CT imaging showed diffusely increased metabolic activity throughout the peritoneum, with no evidence of thoracic or pleural involvement. This case demonstrates the PET/CT findings seen with malignant recurrent peritoneal mesothelioma.
"Second Look" at Journals To Increase Knowledge
Authors: Mandel Weinstein
Journal: JAMA (1969)

To the Editor:—  The usual method of reading only the pertinent articles of subscription medical magazines and then placing the publications on the book shelves, has always seemed to me inadequate treatment of valuable information. To avoid overlooking or forgetting what is new in our profession, it has been my custom for years to review each issue at some time after the first reading. I have considered this a  look, a procedure often resorted to in cancer surgery where one performs a second operation to detect a recurrence that can possibly be removed. 1   The magazine reference section of my own library has been kept up to date with bound volumes of the more important publications, principally surgical, for more than 45 years. As a result, when writing, or searching for detailed information on a particular subject, I have been spared many trips to medical libraries.  My second look
Presence of interchain disulfide bonds between two gene products that compose the secreted form of an antigen-specific suppressor factor.
Authors: M Taniguchi, T Saito, I Takei, T Tokuhisa
Journal: The Journal of Experimental Medicine (1981)

The secreted form of the suppressor T cell factor specific for keyhole limpet hemocyanin derived from the hybridoma 34S-704 was found to consist of the two distinct polypeptide chains, i.e., the antigen-binding and the I-J-encoded chains. They were linked in covalent association with disulfide bonds. The two chains were cleaved by the reduction with dithiothreitol and were easy to reconstitute the active form of TsF. The association of the two distinct chains was suggested to be essential for the expression of the TsF activity.
Psychogenic Nonepileptic Seizures: The Name Matters
Authors: Nitin K. Sethi
Journal: JAMA Neurology (2013)

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 Neurology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Neurology journal
Immunobiology of neural transplants and functional incorporation of grafted dopamine neurons
Authors: Jeffrey B. Blount, Takeshi Kondoh, Lisa L. Pundt, John Conrad, Elizabeth M. Jansen, Walter C. Low
Journal: Behavioral and Brain Sciences (1995)

Abstract In contrast to the views put forth by Stein &amp; Glasier, we support the use of inbred strains of rodents in studies of the immunobiology of neural transplants. Inbred strains demonstrate homology of the major histocompatibility complex (MHC). Virtually all experimental work in transplantation immunology is performed using inbred strains, yet very few published studies of immune rejection in intracerebral grafts have used inbred animals.
American perspective on NHS reforms
Authors: J. Aylward
Journal: BMJ (1991)

for our patients in renal failure should not be greater than our concern for other human beings, even if we are nephrologists or transplant surgeons.Giving a fair price is not the solution for poverty.This is a worldwide problem.Opening such a door will add to the miseries ofThird World countries as they would become the sole source of organs for sale.
Alterations in Glucose Disposal in Sleep-disordered Breathing
Authors: Naresh M. Punjabi, Brock A. Beamer
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

It is well established that sleep-disordered breathing (SDB) is independently associated with insulin resistance, glucose intolerance, and type 2 diabetes mellitus. However, data on whether SDB alters in vivo kinetics of glucose and insulin are lacking.The primary goal of this study was to use the frequently sampled intravenous glucose tolerance test (FSIVGTT) in subjects with and without SDB to model the in vivo kinetics of glucose and insulin. Minimal model analysis of the FSIVGTT data was used to derive parameters of insulin sensitivity, glucose effectiveness (a measure of the ability of glucose to mediate its own disposal), and pancreatic beta-cell function.A total of 118 nondiabetic subjects underwent polysomnography, the FSIVGTT, and body composition measurements including determination of percent body fat. Compared with normal subjects (apnea-hypopnea index < 5 events/h), those with mild, moderate, and severe SDB displayed a 26.7, 36.5 and 43.7% reduction in insulin sensitivity, respectively, independent of age, sex, race, and percent body fat. The disposition index, an integrated measure of pancreatic beta-cell function, was also reduced in patients with moderate to severe SDB. The decrease in insulin sensitivity and the disposition index were correlated with the average degree of oxyhemoglobin desaturation. In contrast, glucose effectiveness was negatively correlated with the frequency of respiratory event-related arousals.The results of this study suggest that, independent of adiposity, SDB is associated with impairments in insulin sensitivity, glucose effectiveness, and pancreatic beta-cell function. Collectively, these defects may increase the risk of glucose intolerance and type 2 diabetes mellitus in SDB.
Screening for neural tube defect: false positive findings on ultrasound and in amniotic fluid.
Authors: N Polanska, D E Burgess, P Hill, J P Bensted, W N Landells
Journal: BMJ (1983)

CommentsThe study shows that high doses of 5-amino salicylic acid and sulphasalazine were equally effective in maintaining remission in patients with ulcerative colitis, but the increased dose appeared to have no real advantage over the lower dose of 12 g previously used.Higher serum concentrations of 5-amino salicylic acid and acetyl 5-amino salicylic acid were recorded in the serum of patients taking the oral 5-amino salicylic acid preparation compared with those taking sulphasalazine.It is possible that the higher doses might be of value in treating acute colitis.We thank Boots Pure Drug Company, Nottingham for supplying placebo sulphasalazine, and Rohm Pharma GMB for preparing the tablets of 5-amino salicylic acid.Inquiries about 5-amino salicylic acid should be sent to Tillotts Laboratory, Henlow, Bedfordshire.
Congenital Aneurysm of the Pulmonary Sinus of Valsalva
Authors: DAVID L. PAGE, GARY M. WILLIAMS
Journal: Circulation (1969)

A case of congenital aneurysm of the pulmonary sinus (sinus of Valsalva) in a 7-year-old child is described. The child met a traumatic death and manifested no symptoms or definite signs of his valvular defect. The heart was of normal weight, and no other abnormalities of the heart or other organs were present. This is the first report of sinus aneurysm of the pulmonary valve. The pathogenetic implications and possible clinical consequences of this defect are discussed.
Biochemical heterogeneity in glutathione synthetase deficiency.
Authors: S P Spielberg, M D Garrick, L M Corash, J D Butler, F Tietze, L Rogers, J D Schulman
Journal: Journal of Clinical Investigation (1978)

Two different clinical syndromes are associated with glutathione synthetase deficiency, one presenting with hemolytic anemia and 5-oxoprolinuria, the other with isolated hemolysis. We have differentiated these disorders on an enzymatic basis. In 5-oxoprolinuria, all cell types examined have grossly deficient enzyme activity and glutathione content. In contrast, in the nonoxoprolinuric variant, erythrocytes have decreased enzyme activity and glutathione content, whereas nucleated cells maintain substantial levels of both. The enzyme in this disorder is unstable in vitro and has shortened survival in intact erythrocytes. Nucleated cells appear able to maintain sufficient enzyme activity and concentrations of glutathione to suppress overproduction of 5-oxoproline.
Role of Conduction Velocity Restitution and Short-Term Memory in the Development of Action Potential Duration Alternans in Isolated Rabbit Hearts
Authors: Sergey Mironov, José Jalife, Elena G. Tolkacheva
Journal: Circulation (2008)

Spatially discordant alternans (SDA) has been linked to life-threatening arrhythmias. The mechanisms underlying SDA development in cardiac tissue remain unclear.We investigated the role of conduction velocity (CV) restitution and short-term memory in the organization and evolution of alternans in action potential duration using high-resolution optical mapping of the epicardial surface in 8 isolated, Langendorff-perfused rabbit hearts. To assess the spatial organization of alternans, we tracked the evolution of nodal lines that separate out-of-phase regions of SDA. We measured the action potential duration heterogeneity index and maximal slope of CV restitution and estimated the effects of short-term memory by calculating time constant of action potential duration accommodation (tau). We found that 2 mechanisms underlie the development of SDA in the heart, leading to 2 distinct behaviors of nodal lines. The first mechanism is based on steep CV restitution and is associated with small tau and stable nodal lines. The second mechanism is associated with short-term memory (large tau) and is characterized by shallow CV restitution and unstable behavior of nodal lines. The maximum slope of the CV restitution was steeper (18.16+/-3.34 m/s(2)) and tau was smaller (tau=4.31+/-0.33 stimuli) for areas with stable nodal lines than for areas with unstable nodal lines (6.32+/-0.96 m/s(2) and tau=10.3+/-1.84 stimuli; P<0.01).Our results provide new insight into the mechanisms underlying SDA formation in the rabbit heart. Specifically, our results suggest that a new mechanism associated with short-term memory underlies SDA formation in the heart, in addition to steep CV restitution.
Are GPs who specialise in dermatology effective?: High cost of general practitioners with special interests is a fallacy
Authors: Cornelius J Crowley
Journal: BMJ (2006)

We evaluated the pharmacological profile of ritobegron [KUC-7483; (−)-ethyl 2-[4-(2-{[(1<i>S</i>,2<i>R</i>)-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino}ethyl)-2,5-dimethylphenyloxy]acetate monohydrochloride] and its effects on the bladder in cynomolgus monkeys by in vitro and in vivo experiments. In vitro, ritobegron decreased the resting tension of the isolated bladder in a concentration-dependent manner (EC<sub>50</sub> 8.2 ± 2.3 × 10<sup>−7</sup> M; maximal relaxation 88.7 ± 3.7%). The β<sub>3</sub>-adrenoceptor (AR) antagonist 3-(2-allylphenoxy)-1-[(1<i>S</i>)-1,2,3,4-tetrahydronaphth-1-ylamino]-(2<i>S</i>)-2-propanol hydrochloride (SR58894A) produced a rightward shift of this concentration-response curve without altering the maximal response (p<i>K</i><sub>B</sub> value 6.56 ± 0.35). In isolated atria, ritobegron increased the atrial rate only at high concentrations (EC<sub>50</sub> 6.5 ± 1.2 × 10<sup>−5</sup> M). Ritobegron had no effect on tracheal contraction at concentrations from 10<sup>−9</sup> to 10<sup>−4</sup> M, and even at the highest concentration tested, 10<sup>−3</sup> M, the maximal relaxation it induced was only 26.7 ± 8.1%. Tests of the selectivity of ritobegron for the bladder gave values of 79.3- and 1200-fold higher versus atria and trachea, respectively. In the in vivo study ritobegron significantly decreased intravesical pressure (ED<sub>50</sub> 1.44 mg/kg) without affecting either mean blood pressure or heart rate. In conclusion, ritobegron displayed potent and selective β<sub>3</sub>-AR agonistic activity and relaxed the monkey isolated bladder, and in vivo it decreased intravesical pressure without affecting cardiovascular parameters. These results suggest that ritobegron may be a promising potential agent for the treatment of overactive bladder.
Leukosialin (CD43)-major histocompatibility class I molecule interactions involved in spontaneous T cell conjugate formation.
Authors: J Stöckl, O Majdic, P Kohl, W F Pickl, J E Menzel, W Knapp
Journal: The Journal of Experimental Medicine (1996)

Resting T cells spontaneously adhere in a selective manner to potent accessory cells, such as dendritic cells (DC) and lymphoblastoid B blasts (LCL). Here we demonstrate that leukosialin (CD43) and major histocompatibility complex class I molecules (MHC-I) might play a critical role in this process. T cell conjugate formation with monocyte-derived DC (md-DC) and LCL could be strongly inhibited by either preincubating T cells with Fab fragments of CD43 monoclonal antibody (mAb) 6F5 or by preincubating md-DC or LCL with MHC-I mAb W6/32. Intact CD43 mAb 6F5, in contrast to monovalent Fab fragments, enhanced T cell adhesiveness by transactivating CD2 binding to CD58 molecules. Interestingly, induction of this proadhesive signal via CD43 with intact 6F5 mAb was found to revert mAb W6/32-mediated inhibition of T cell conjugate formation. These observations indicated that CD43 cross-linkage mimics and monovalent mAb 6F5 inhibits interaction of T cell CD43 with a stimulatory ligand on opposing cells, presumably MHC-I. For the demonstration of direct physical interaction between CD43 on T cells and MHC-I-coated beads it was necessary, however, to ligate CD2 on T cells with a stimulatory pair of CD2 mAbs (VIT13 plus TS2/18). This suggests that CD2 ligation crosswise upregulates CD43 binding avidity for MHC-I and that both adhesion molecule pairs (CD43/MHC-I and CD2/CD58) act in concert to induce and mediate T cell conjugate formation with certain cell types.
Effective Care in Pregnancy and Childbirth, vol 1: Pregnancy, parts I-V; vol II: Childbirth
Authors: Edwin M. Gold
Journal: JAMA (1990)

In management of patients during pregnancy, labor, and delivery, there are many therapeutic options open to the clinician. Marked variations in patterns of care and options for therapeutic management exist from country to country, institution to institution, and among individual health professionals. Thus, disagreements and differences of opinion exist as to the most effective approach. How can past and present obstetric practices best be evaluated as to their efficacy? <i>Effective Care in Pregnancy and Childbirth</i>attempts to answer this question. As stated by the editors in the preface, they have embarked upon a systematic review of randomized trials of obstetric practices, which is an innovative achievement and "represents a real milestone in the history of randomized trials and in the evaluation of care." Data for analysis were developed by using the MEDLINE database to identify studies that met the editors' criteria, doing a systematic hand search of over 60 key
Prognostic and Predictive Impact of Intrinsic Biological Classification by Immunohistochemistry (IHC) and QPCR for Adjuvant Tamoxifen in Pre-Menopausal Breast Cancer: Results from the NCIC CTG MA.12 Trial.
Authors: S. Chia, K. Ung, V. Bramwell, D. Tu, C. Perou, M. Ellis, P. Bernard, T. Vickery, E. Mardis, M. Cheang, K. Pritchard, L. Shepherd, T. Nielsen
Journal: Cancer Research (2009)

Abstract Background: Aside from the estrogen receptor (ER), there is no other validated predictive biomarker for the magnitude of benefit from tamoxifen. Gene expression profiling has clearly demonstrated that breast cancer is a heterogeneous disease, and has re-classified breast cancer into intrinsic subtypes. We have utilized material from a prospective randomized trial of tamoxifen versus placebo in pre-menopausal women with primary breast cancer who have completed adjuvant chemotherapy (NCIC CTG MA.12 Trial) in order to evaluate the prognostic and predictive significance of intrinsic subtypes as classified by both IHC and qPCR.Methods: A tissue microarray (TMA) was constructed from 492/672 (72%) of the study population. A panel of six IHC antibodies (ER, PR, HER2, EGFR, CK 5/6 and Ki67) was utilized with established cut-offs to define the intrinsic subtypes of luminal A, luminal B, HER-2 and basal. Total RNA from 403/672 (60%) patients was sufficient for intrinsic subtyping with a 50 gene predictor (PAM50) by qPCR. In 354 cases intrinsic subtyping was performed by both methods.Results: There were no significant differences between the initial study population and the TMA series in baseline characteristics. Within the TMA series 39% (n=190) were classified as luminal A, 31% luminal B (n=143) [20% by Ki67 and 11% by HER2], 7% HER2-enriched and 17% basal-like by IHC. Intrinsic subtypes were prognostic with luminal A (5 year 93% OS) having the best outcome and basal-like (5 year 71% OS) the worst (p=0.0086 Wilcoxon). Tamoxifen appeared to benefit the luminal B cancers most (5 year DFS HR 0.67; 95% CI 0.39-1.16: p=0.077) when compared to placebo, however no subtype, nor ER status alone, predicted benefit of tamoxifen in this correlative study. Data for concordance for subtyping by IHC and qPCR as well as prognostic/predictive impact by qPCR subtyping will be presented.Conclusions: Intrinsic biological classification of breast cancer is important for prognosis and may have predictive value for relative benefit to tamoxifen. Further validation of these results are required. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4056.
Effects of breast conservation on psychological morbidity associated with diagnosis and treatment of early breast cancer.
Authors: L J Fallowfield, M Baum, G P Maguire
Journal: BMJ (1986)

Psychiatric morbidity was assessed in 101 women treated for early breast cancer (T0,1,2,N0,1,M0). Patients had expressed no strong preference for treatment, so were randomised to either mastectomy or breast conservation. The incidence of anxiety states or depressive illness, or both, among women who underwent mastectomy was high (33%) and comparable with that found in other studies. Slightly more of the patients who underwent a lumpectomy followed by radiotherapy had affective disorders, 38% having an anxiety state, depressive illness, or both. These findings question the view that mutilating treatment is predominantly responsible for the measurable psychiatric morbidity reported previously. Counselling services should be provided for all women treated for breast cancer, not just those who undergo mastectomy.
Atrial Fibrillation -- The Last Big Hurdle in Treating Supraventricular Tachycardia
Authors: Hein J.J. Wellens
Journal: New England Journal of Medicine (1994)

Atrial fibrillation is the most common chronic tachycardia1. Even in the absence of other cardiac abnormalities, the loss of effective atrial contraction and the inappropriately rapid ventricular rate during arrhythmia result in depressed cardiac function2 and promote the formation of intracardiac thrombi. This makes atrial fibrillation the most common cardiac cause of stroke. Several factors promote the development of atrial fibrillation, such as age, valvular disease, congestive heart failure, hypertension, and diabetes mellitus1. The incidence of this type of arrhythmia is increasing, not only because the population is aging, but also because more patients are surviving the acute . . .