tbuckley/cabot-search huggingface dataset:
The Apaf-1/caspase-9 apoptosome is dispensable for Fas-mediated apoptosis in type II Jurkat T-lymphocytes
Authors: Mary Shawgo, John Robertson
Journal: Cancer Research (2008)

4370  Stimulation of the Fas receptor leads to apoptosis upon activation of caspase-8 within the death-inducing signaling complex (DISC). Two distinct signaling pathways of Fas-induced apoptosis have been described that differ in the extent of DISC formation and mitochondrial involvement. In type I cells, robust caspase-8 activation is followed closely by cleavage and activation of caspase-3 in a mitochondria-independent manner. In type II cells, initial caspase-8 activation is low and amplification of this signal is thought to rely heavily on the engagement of the mitochondrial apoptotic pathway by caspase-8-mediated cleavage of the pro-apoptotic Bcl-2 family protein Bid. In this regard, a commonly held view is that anti-apoptotic Bcl-2 proteins, such as Bcl-2 and Bcl-xL, are able to inhibit Fas-induced apoptosis in type II but not type I cells. To help elucidate the underlying role of mitochondria during receptor-mediated apoptosis in so-called type II cells, we established distinct clones of Jurkat T-lymphocytes (clone E6.1) in which the mitochondrial apoptotic pathway had been ablated due to stable overexpression of Bcl-2/Bcl-xL or depletion of Apaf-1. Notably, these cell lines were equally resistant to apoptosis induced by genotoxic stress. Cells overexpressing either Bcl-2 or Bcl-xL were also protected from apoptosis induced by anti-Fas antibody, whereas Apaf-1-deficient Jurkat cells were sensitive to anti-Fas, displaying robust caspase-8 and -3 activation, Bid cleavage, Bak activation, mitochondrial membrane depolarization, and the release of cytochrome c and Smac/DIABLO, events that were all inhibited by pre-treating cells with the caspase-3-like inhibitor z-DEVD-fmk. Significantly, pretreatment of the Bcl-xL-overexpressing cells with a Smac mimetic sensitized these cells to treatment with anti-Fas. Combined, these data would suggest that it is the release of pro-apoptotic factors from the mitochondrial intermembrane space, rather than the mitochondrial apoptotic pathway per se, that is essential for apoptosis in response to anti-Fas in type II Jurkat cells. (Supported by NIH grants K22 ES011647 (to J.D.R.) and P20 RR016475)
Regulating Medical Work, by Judith Alsop, Linda Mulcahy
Authors: M. M Rosenthal
Journal: BMJ (1997)

Judith Alsop, Linda Mulcahy / Open University Press, £45, pp 230 / ISBN 0 335 19404 4

Monopoly over medical knowledge lies at the heart of any meaningful discussion of professional regulation. And medical uncertainty lies in the deepest recesses of medical knowledge. Without recognition of this, discussions of professional regulation remain incomplete.

Regulating Medical Work is an impressive attempt to bring together a variety of research on formal and informal regulation of the medical profession and discuss it in the context of social science analysis. The authors review “the web of regulation,” both formal and informal, found in various institutions and organisations with regulatory responsibility. Included are the NHS, General Medical Council, health service commissioner, the courts, the complaints procedures, and informal collegial efforts. The authors pose various conceptual models of state, institutional, and collegial behaviour as well as providing a summary of the current empirical research, where it exists.

The authors recognise the importance of the monopoly of medical knowledge and medical uncertainty. In their concluding observations they point out that, despite the increase in regulation across the agencies and organisations discussed, medical knowledge is “unique” and the profession remains in the dominant position to decide what constitutes appropriate medical practice …
Trends in Women Among Medical School Faculty
Authors: Bonnie M Simpson
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
Inhibition of heat-shock protein 90 (Hsp90) disrupts mutliple pro-angiogenic signaling pathways in gastric cancers cells in vitro and reduces tumor growth and angiogenesis in vivo
Authors: Sven A. Lang, Dagmar Klein, Christine Wagner, Corina Desousa, Ulrich Bolder, Hans J. Schlitt, Edward K. Geissler, Oliver Stoeltzing
Journal: Cancer Research (2006)

247   Various oncogenic signaling pathways have been implicated in gastric cancer growth and angiogenesis which include hypoxia-inducible-factor-1α (HIF-1α), epidermal growth factor receptor (EGFR) and HER-2/neu. Recently, heat-shock protein 90 (Hsp90) has been identified to be critical for activation of intracellular signaling cascades and functionality of oncogenic proteins, such as HIF-1α and HER-2. Thus, we hypothesized that blocking Hsp90 would impair EGF-mediated angiogenic signaling in gastric cancer cells  in vitro  and subsequently inhibit angiogenesis and tumor growth  in vivo . Human gastric cancer cells (TMK-1, KKLS) were used to study effects of specific Hsp90 inhibitors (17AAG, 17DMAG)  in vitro  and  in vivo . Effects of 17AAG on EGF-induced activation of signaling intermediates were investigated by Western blotting. Expression of VEGF upon 17AAG treatment was determined by PCR and ELISA. Changes in cell migration and invasion (mediated by EGF) were evaluated in  in vitro  assays, in the presence or absence of 17AAG. For  in vivo  experiments, the water soluble compound 17DMAG was used (25mg/kg; 3x/wk). Effects of Hsp90 inhibition on tumor growth and angiogenesis were investigated in a xenogenic tumor model with subcutaneously implanted cancer cells. Mice received either 17DMAG or vehicle by intraperitoneal injection.  In vitro , 17AAG inhibited constitutive and inducible activation of MAPK/Erk, PI-3K/Akt and disrupted HER-2 and STAT3 activation in gastric cancer cells. Furthermore, 17AAG diminished EGF and hypoxia induced nuclear HIF-1α. Interestingly, nuclear CREB (a mediator of HIF-1α independent hypoxia signaling) was also diminished. By ELISA, 17AAG treatment significantly reduced basal and EGF- induced VEGF secretion in cancer cells (P in vitro (P In vivo , treatment with 17DMAG led to a significant reduction in tumor growth rates (P in vitro  and decreased tumor growth and angiogenesis  in vivo . Thus, inhibitors of Hsp90 could prove to be a valuable addition to antiangiogenic/antineoplastic therapy regimens for the treatment of gastric cancer.
Cholecystectomy in Sickle Cell Anemia Patients: Perioperative Outcome of 364 Cases From the National Preoperative Transfusion Study
Authors: Charles M. Haberkern, Lynne D. Neumayr, Eugene P. Orringer, Ann N. Earles, Shanda M. Robertson, Dennis Black, Miguel R. Abboud, Mabel Koshy, Olajire Idowu, Elliott P. Vichinsky
Journal: Blood (1997)
An Interglomerular Circuit Gates Glomerular Output and Implements Gain Control in the Mouse Olfactory Bulb
Authors: Arkarup Banerjee, Fred Marbach, Francesca Anselmi, Matthew S. Koh, Martin B. Davis, Pedro Garcia da Silva, Kristen Delevich, Hassana K. Oyibo, Priyanka Gupta, Bo Li, Dinu F. Albeanu
Journal: Neuron (2015)
Interleukin (IL)-22, IL-17, IL-23, IL-8, vascular endothelial growth factor and tumour necrosis factor-α levels in patients with psoriasis before, during and after psoralen-ultraviolet A and narrowband ultraviolet B therapy
Authors: S. Coimbra, H. Oliveira, F. Reis, L. Belo, S. Rocha, A. Quintanilha, A. Figueiredo, F. Teixeira, E. Castro, P. Rocha-Pereira, A. Santos-Silva
Journal: British Journal of Dermatology (2010)

Several cross-sectional studies have shown that different cytokines and growth factors are enhanced in psoriasis.We aimed to understand the role/relation of interleukin (IL)-22, IL-17, IL-23, IL-8, vascular endothelial growth factor (VEGF) and tumour necrosis factor (TNF)-α in psoriasis vulgaris, addressing their levels and changes before, during and after psoralen-ultraviolet A (PUVA) and narrowband ultraviolet B (NB-UVB) treatment.A cross-sectional and a longitudinal study (n = 34) - before (T0) and at 3 (T3), 6 (T6) and 12 (T12) weeks of NB-UVB and PUVA therapy - were performed; 17 patients started NB-UVB and 17 PUVA, and IL-22, IL-17, IL-23, IL-8, TNF-α and VEGF levels were evaluated.At T0, compared with controls (n = 20), all the parameters were significantly higher in patients, except for TNF-α. Both NB-UVB and PUVA treatment gave, at T3, a significant decrease in TNF-α and IL-23; IL-22 and IL-17 decreased significantly at T6; all parameters and Psoriasis Area and Severity Index decreased significantly at T12. However, in both groups, at T12, VEGF was still significantly higher than control.Psoriasis seems to be a complex disease in which the cytokine network is disturbed, namely in levels of IL-22, IL-17, IL-23, IL-8, TNF-α and VEGF. NB-UVB and PUVA follow-up studies suggested that the reduction in the IL-23/Th17 axis might be important in the pathogenic mechanisms of psoriasis. Further follow-up studies of patients with psoriasis treated with these and other therapies could be very helpful for the understanding of the disturbance in the cytokine network in psoriasis and indirectly in its pathogenesis.
Prebiopsy Multiparametric Magnetic Resonance Imaging for Prostate Cancer Diagnosis in Biopsy-naive Men with Suspected Prostate Cancer Based on Elevated Prostate-specific Antigen Values: Results from a Randomized Prospective Blinded Controlled Trial
Authors: Panu P. Tonttila, Juha Lantto, Eija Pääkkö, Ulla Piippo, Saila Kauppila, Eveliina Lammentausta, Pasi Ohtonen, Markku H. Vaarala
Journal: European Urology (2015)
Audiotaping of Informed Consent
Authors: Carmen E Guerra
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 Journals 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 2024 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
Abstract 13535: The Synergistic Effects of Incretin-related Drugs for the Treatment of Pulmonary Arterial Hypertension
Authors: Susumu Hosokawa, Go Haraguchi, Yasuhiro Maejima, Shozaburo Doi, Mitsuaki Isobe
Journal: Circulation (2014)

Introduction: A growing body of evidence suggests that inflammation plays a crucial role in the development of pulmonary arterial hypertension (PAH). Dipeptidyl peptidase-4 (DPP-4; also known as CD26), a protease which degrades incretin hormones such as glucagon-like peptide-1 (GLP-1), modulates inflammatory processes by regulating activity of T cells through co-stimulatory pathway. Hypothesis: Incretin-related drugs, including both DPP-4 inhibitors and GLP-1 receptor agonists, suppress the progression of PAH by attenuating inflammatory response of PA. Methods: Sprague Dawley rats were injected monocrotaline to induce PAH (N=80). After 14 days from PAH induction, these rats were treated with alogliptin, a DPP-4 inhibitor (M+A, N=20), liraglutide, a GLP-1 receptor agonist (M+L, N=20), both of these drugs (M+A+L, N=20), or vehicle (M, N=20). Results: A significant increase of survival was observed on days 30 after PAH induction both in the M+A and M+L compared to the M (M+A: 45%* vs. M+L: 60%* vs. M: 5%, * p &lt;0.05). Both alogliptin and liraglutide markedly improved right ventricular pressure (M+A: 33±4.1mmHg* vs. M+L: 26±1.9mmHg* vs. M: 85.9±1.2mmHg, * p &lt;0.05). mRNA levels of both CD28 and CD86, co-stimulators of T cells, significantly decreased and the level of caveolin-1 markedly increased in lung tissues of the M+A compared to those in the M. mRNA levels of both Tissue Factor (TF) and PAI-1 significantly decreased in lung tissues of the M+L than those in the M. Consistently, survival of rats in the M+A+L was the highest (65%) among all of the groups of PAH rats. Coimmunoprecipitation assays revealed that CD26 in T cells physically interacted with caveolin-1 in rat pulmonary vascular smooth muscle cells (rPASMCs). Immunoblot analyses showed that alogliptin suppressed caveolin-1 phosphorylation in rPASMCs. Furthermore, reporter gene assays demonstrated that alogliptin significantly inhibited the transcriptional activity of NF-κB. Conclusions: These results suggest that DPP-4 inhibition and stimulation of GLP-1 receptors synergistically mediate salutary effects on monocrotaline-induced PAH by modulating T cell activity and TF-associated signaling pathway. Thus, incretin-related drugs have a potential as a novel therapeutic tool for PAH.
Comparison between genomic alterations of primary breast tumors and their corresponding sentinel lymph node metastatic lesions
Authors: Savana L. Santos, Iglenir J. Cavalli, Enilze M. Ribeiro, Cicero A. Urban, Rubens S. Lima, Bassem R. Haddad, Luciane R. Cavalli
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4211 

The sentinel lymph node (SLN) is the first node in the axilla to harbor malignant cells in breast tumors with metastasis, and its positivity is an indication for axillary lymph node dissection. Characterization of genetic alterations in the SLN metastatic lesions is a logical step for better defining the evolution of primary tumors to a metastatic state, and may represent the initial genetic event that occur early in the metastatic process, before distant metastasis takes place. Several studies have been performed to “profile” breast tumors and their metastatic lesions in distant axillary lymph nodes, but none has looked at metastasis in SLN. In addition, very few of these studies have been performed in paired primary tumors and metastatic lesions from the same patient. In an effort to precisely characterize early genomic changes that are associated with and may predispose to metastasis, we initiated this study to compare genomic alterations between primary breast tumors and their corresponding sentinel lymph node metastatatic lesions using comparative genomic hybridization (CGH). Here, we report our results from the analysis of the 1st ten cases (paired samples). The tissue blocks were obtained from the Hospital Nossa Senhora das Gracas, Brazil. CGH was performed using tumor DNA obtained from malignant cells isolated by microdissection from paraffin embedded archival material. Chromosomal abnormalities were observed in all 10 cases studied, in the primary lesions as well as in the SLN metastasis. The most frequent gains (+) and losses (−) observed were: −1p31∼p21, +17, +19 and +20. Theses alterations were observed in both groups. Gain on chromosome 20 was the most frequently observed in the primary tumors group, whereas losses on 1p31∼p21 and gains on chromosomes 17 and 19 were equally observed in both groups. An additional number of paired samples of primary tumors and corresponding SLN metastatic lesions are currently being evaluated. This study will allow the assessment of the degree of clonal divergence and genetic heterogeneity that characterize the metastatic process. Identification of genetic alterations present in the SLN of the breast will be important to detect early genetic alterations that occur in the metastatic process. These alterations can potentially be used as additional prognostic markers that can help in the reduction or elimination of the need for invasive surgical procedures, such as axillary lymph node dissection, to predict outcome.
Abstract P111: Sleep duration is associated with serum osteocalcin level in an elderly Korean population: the Korean Urban and Rural Elderly (KURE) study
Authors: Ju-Mi Lee, Hansol Choi, Kyung Min Kim, YooSik Youm, Yumie Rhee, Chang Oh Kim, Hyeon Chang Kim
Journal: Circulation (2014)

Importance: Association between sleep duration and health related outcome studies have been published consistently. However there have been few studies of the association between sleep duration and bone formation in elderly. Objective: The aim of this study is to examine association between sleep duration and serum osteocalcin level in an elderly Korean population. Design: Cross sectional analysis using baseline cohort data. Setting: Community based setting Participants: Among the total of 927 participants, we excluded 1 participant because of the absence on sleep duration answer. A final total of 926 participants (624 women and 302 men aged 64-87 years) who completed baseline health examination in 2012 were enrolled in this study. Measurement: Sleep duration was measured by interviewer-assisted questionnaire. Participants answered their regular time of going to bed, time of opening eyes in the morning, and time of regular nap using open questions during the passing year. Serum osteocalcin level, a known biomarker of osteogenesis, was measured by electrochemiluminescence immunoassay method in the central research laboratory. The association between sleep duration (minutes/day) and serum osteoclacin level (ng/ml) was assessed by multiple linear regression analysis. Results: In the total population, sleep duration had significant association with serum osteocalcin level (ß=-0.008, p=0.013). One hour increase in sleep duration was associated with 0.48 ng/ml increase in serum osteocalcin level. This association remained after controlling for age, sex, body mass index, cigarette smoking, alcohol drinking, physical activity, and serum 25(OH) vitamin D (ß=0.012, p&lt;0.001). This association was consistent before and after adjusting confounders in women (ß=-0.010, p=0.019, ß=-0.011, p=0.009, respectively) and men (ß=-0.013, p=0.012, ß=-0.013, p=0.011, respectively). Conclusions: Our findings suggest that longer sleep duration is associated with higher bone formation process in an elderly of Korean.
Abstract 12648: Deletion of 12/15 Lipoxygenase Improves Left Ventricle Function and Survival by Resolving Inflammation Post Myocardial Infarction
Authors: Vasundhara Kain, Kevin A Ingle, Janusz Kabarowski, Sumanth D Prabhu, Ganesh V Halade
Journal: Circulation (2014)

12/15 lipoxygenase (LOX) is crucial in the inflammatory process leading to diabetes and atherosclerosis. However, the role of 12/15 LOX in myocardial infarction (MI) and left ventricle (LV) remodeling is unclear. We assessed the role of 12/15 LOX in resolving inflammation in post-MI LV remodeling. 8-12 weeks old C57BL/6J wild-type (WT; n=67) and 12/15 LOX (LOX –/– ; n=78) male mice were subjected to permanent coronary artery ligation surgery and monitored through day (d)1 and d5. No MI surgery mice were maintained as d0 naïve controls. LOX -/- mice showed higher survival rate, improved fractional shortening with reduced remodeling and edema index than WT at d1 and d5 post-MI (all p&lt;0.05). LOX -/- mice showed increased Cxcl5 expression at d1 post-MI, consistent with stimulated neutrophil recruitment in the infarct region that was decreased at d5 compared to WT. LOX -/- mice infarct had increased expression of Ccl2 and Cxcl1, that stimulated an earlier recruitment of monocytes with increased macrophages population at d5 (all p&lt;0.05) compared to WT. The altered kinetics of immune cells post-MI indicates a rapid resolving phase, through increase in alternative macrophage phenotypes with reduced collagen density in LOX -/- mice compared to WT mice at d5 post-MI. LOX -/- mice showed a coordinated COX-1 and COX-2 response at d1 post MI, leading to an evident increase in 5-LOX and hemoxygenase-1 (HO-1) at d5 post-MI. 12/15 LOX deletion enhanced the recruitment of alternative macrophages with secretion of HO-1 to resolve inflammation. In-vitro addition of LOX metabolite 12 hydroxyeicosatetraenoic acid to LOX -/- fibroblast induced early expression of COX-2 and 5-LOX compared to WT, indicating 5LOX role in resolution of inflammation. Post-MI increased expression of TIMP-1 and decrease in MMP-9 at d1 and α-SMA at d5 in LOX -/- mice suggested controlled differentiation of fibroblast-to-myofibroblast which is key event during ventricular tissue repair and resolving phase. This change is supported by increased expression of tgf-βi, ctgf and admats-2 (all P&lt;0.05) at d5 post MI. In conclusion, absence of 12/15 LOX improves post-MI survival rates and attenuates LV dysfunction by resolving inflammation through coordination of 5-LOX and HO-1 as key inflammation resolving enzymes.