tbuckley/cabot-search huggingface dataset:
Studies on the mechanisms of macrophage activation. II. Parasite destruction in macrophages activated by supernates from concanavalin A-stimulated lymphocytes.
Authors: Y Buchmüller, J Mauel
Journal: The Journal of Experimental Medicine (1979)

Activation of mouse peritoneal exudate macrophages, as evidenced by destruction of the intracellular protozoan parasite Leishmania enriettii, was obtained by incubation with supernates from concanavalin A (Con A)-stimulated syngeneic spleen cells. Parasites were not destroyed in macrophages exposed to control media. Supernate-induced activation was independent of the presence of Con A. The activating principle (macrophage activating factor, or MAF) was produced by Con A-stimulated lymphocytes in presence or absence of serum. In absence of serum, MAF synthesis was highest at Con A concentrations far below those required in serum-containing media. MAF production was reduced at Con A concentrations of 10 microgram/ml or above, probably a result of toxicity of the lectin for lymphocytes. MAF was detectable after 24 h of lymphocyte stimulation and increased up to 72 h; production appeared to be independent of DNA synthesis. Serum-free MAF was inactive when tested as such on macrophages. Full activity could be restored by addition of nanogram amounts of endotoxin or of FCS before assay. Endotoxin also considerably potentiated MAF activity in serum-containing supernates. Full intracellular parasite destruction was observed after contact of macrophages with MAF for 20 h. The continuous presence of MAF was not necessary for activation; a 10-h pulse was sufficient to induce macrophages to destroy all intracellular microorganisms within the next 38 h.
Large Arteriovenous Malformation in an Adolescent Presenting With First Seizure
Authors: Jennifer L. McKinney
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
Vinorelbine and cisplatin in metastatic squamous cell carcinoma of the oesophagus: response, toxicity, quality of life and survival
Authors: T. Conroy, P.-L. Etienne, A. Adenis, M. Ducreux, B. Paillot, J. Oliveira, J.-F. Seitz, E. Francois, E. Van Cutsem, D.J.T. Wagener, F. Kohser, S. Daamen, M. Praet, T. Gorlia, B. Baron, J. Wils
Journal: Annals of Oncology (2002)
Protein Kinase C βII and PKCι/λ: Collaborating Partners in Colon Cancer Promotion and Progression
Authors: Nicole R. Murray, Justin Weems, Ursula Braun, Michael Leitges, Alan P. Fields
Journal: Cancer Research (2009)

Abstract We previously showed that elevated expression of either protein kinase CβII (PKCβII) or PKCι/λ enhances colon carcinogenesis in mice. Here, we use novel bitransgenic mice to determine the relative importance of PKCβII and PKCι/λ in colon carcinogenesis in two complimentary models of colon cancer in vivo. Bitransgenic mice overexpressing PKCβII and constitutively active PKCι (PKCβII/caPKCι) or kinase-deficient, dominant-negative PKCι (PKCβII/kdPKCι) in the colon exhibit a similar increase in colon tumor incidence, tumor size, and tumor burden in response to azoxymethane (AOM) when compared with nontransgenic littermates. However, PKCβII/kdPKCι mice develop predominantly benign colonic adenomas, whereas PKCβII/caPKCι mice develop malignant carcinomas. In contrast, PKCβ-deficient (PKCβ−/−) mice fail to develop tumors even in the presence of caPKCι. Our previous data indicated that PKCβII drives tumorigenesis and proliferation by activating β-catenin/Apc signaling. Consistent with this conclusion, genetic deletion of PKCβ has no effect on spontaneous tumorigenesis in Apcmin/+ mice. In contrast, tissue-specific knockout of PKCλ significantly suppresses intestinal tumor formation in Apcmin/+ mice. Our data show that PKCβII and PKCι/λ serve distinct, nonoverlapping functions in colon carcinogenesis. PKCβII is required for AOM-induced tumorigenesis but is dispensable for tumor formation in ApcMin/+ mice. PKCι/λ promotes tumor progression in both AOM- and Apcmin/+-induced tumorigenesis. Thus, PKCβII and PKCι, whose expression is elevated in both rodent and human colon tumors, collaborate to drive colon tumor formation and progression, respectively. [Cancer Res 2009;69(2):656–62]
Mitomycin-Induced Pulmonary Veno-Occlusive Disease
Authors: Frédéric Perros, Sven Günther, Benoit Ranchoux, Laurent Godinas, Fabrice Antigny, Marie-Camille Chaumais, Peter Dorfmüller, Aurélie Hautefort, Nicolas Raymond, Laurent Savale, Xavier Jaïs, Barbara Girerd, Vincent Cottin, Olivier Sitbon, Gerald Simonneau, Marc Humbert, David Montani
Journal: Circulation (2015)

Background— Pulmonary veno-occlusive disease (PVOD) is an uncommon form of pulmonary hypertension characterized by the obstruction of small pulmonary veins and a dismal prognosis. PVOD may be sporadic or heritable because of biallelic mutations of the EIF2AK4 gene coding for GCN2. Isolated case reports suggest that chemotherapy may be a risk factor for PVOD. Methods and Results— We reported on the clinical, functional, and hemodynamic characteristics and outcomes of 7 cases of PVOD induced by mitomycin-C (MMC) therapy from the French Pulmonary Hypertension Registry. All patients displayed squamous anal cancer and were treated with MMC alone or MMC plus 5-fluoruracil. The estimated annual incidence of PVOD in the French population that have anal cancer is 3.9 of 1000 patients, which is much higher than the incidence of PVOD in the general population (0.5/million per year). In rats, intraperitoneal administration of MMC induced PVOD, as demonstrated by pulmonary hypertension at right-heart catheterization at days 21 to 35 and major remodeling of small pulmonary veins associated with foci of intense microvascular endothelial-cell proliferation of the capillary bed. In rats, MMC administration was associated with dose-dependent depletion of pulmonary GCN2 content and decreased smad1/5/8 signaling. Amifostine prevented the development of MMC-induced PVOD in rats. Conclusions— MMC therapy is a potent inducer of PVOD in humans and rats. Amifostine prevents MMC-induced PVOD in rats and should be tested as a preventive therapy for MMC-induced PVOD in humans. MMC-induced PVOD in rats represents a unique model to test novel therapies in this devastating orphan disease.
Cardiac-specific overexpression of AT1 receptor mutant lacking G q/G i coupling causes hypertrophy and bradycardia in transgenic mice
Authors: P. Zhai
Journal: Journal of Clinical Investigation (2005)

Ang II type 1 (AT1) receptors activate both conventional heterotrimeric G protein–dependent and unconventional G protein–independent mechanisms. We investigated how these different mechanisms activated by AT1 receptors affect growth and death of cardiac myocytes in vivo. Transgenic mice with cardiac-specific overexpression of WT AT1 receptor (AT1-WT; Tg-WT mice) or an AT1 receptor second intracellular loop mutant (AT1-i2m; Tg-i2m mice) selectively activating Gαq/Gαi-independent mechanisms were studied. Tg-i2m mice developed more severe cardiac hypertrophy and bradycardia coupled with lower cardiac function than Tg-WT mice. In contrast, Tg-WT mice exhibited more severe fibrosis and apoptosis than Tg-i2m mice. Chronic Ang II infusion induced greater cardiac hypertrophy in Tg-i2m compared with Tg-WT mice whereas acute Ang II administration caused an increase in heart rate in Tg-WT but not in Tg-i2m mice. Membrane translocation of PKCε, cytoplasmic translocation of Gαq, and nuclear localization of phospho-ERKs were observed only in Tg-WT mice while activation of Src and cytoplasmic accumulation of phospho-ERKs were greater in Tg-i2m mice, consistent with the notion that Gαq/Gαi-independent mechanisms are activated in Tg-i2m mice. Cultured myocytes expressing AT1-i2m exhibited a left and upward shift of the Ang II dose-response curve of hypertrophy compared with those expressing AT1-WT. Thus, the AT1 receptor mediates downstream signaling mechanisms through Gαq/Gαi-dependent and -independent mechanisms, which induce hypertrophy with a distinct phenotype.
Reactive Oxygen Species-Regulated Signaling Pathways in Diabetic Nephropathy
Authors: Hi Bahl Lee, Mi-Ra Yu, Yanqiang Yang, Zongpei Jiang, Hunjoo Ha
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Diabetic nephropathy is characterized by excessive deposition of extracellular matrix (ECM) in the kidney. TGF-β1 has been identified as the key mediator of ECM accumulation in diabetic kidney. High glucose induces TGF-β1 in glomerular mesangial and tubular epithelial cells and in diabetic kidney. Antioxidants inhibit high glucose-induced TGF-β1 and ECM expression in glomerular mesangial and tubular epithelial cells and ameliorate features of diabetic nephropathy, suggesting that oxidative stress plays an important role in diabetic renal injury. High glucose induces intracellular reactive oxygen species (ROS) in mesangial and tubular epithelial cells. High glucose-induced ROS in mesangial cells can be effectively blocked by inhibition of protein kinase C (PKC), NADPH oxidase, and mitochondrial electron transfer chain complex I, suggesting that PKC, NADPH oxidase, and mitochondrial metabolism all play a role in high glucose-induced ROS generation. Advanced glycation end products, TGF-β1, and angiotensin II can also induce ROS generation and may amplify high glucose-activated signaling in diabetic kidney. Both high glucose and ROS activate signal transduction cascade (PKC, mitogen-activated protein kinases, and janus kinase/signal transducers and activators of transcription) and transcription factors (nuclear factor-κB, activated protein-1, and specificity protein 1) and upregulate TGF-β1 and ECM genes and proteins. These observations suggest that ROS act as intracellular messengers and integral glucose signaling molecules in diabetic kidney. Future studies elucidating various other target molecules activated by ROS in renal cells cultured under high glucose or in diabetic kidney will allow a better understanding of the final cellular responses to high glucose. E-mail: [email protected]
Micro-masters of glioblastoma biology and therapy: increasingly recognized roles for microRNAs
Authors: D. Floyd, B. Purow
Journal: Neuro-Oncology (2014)

MicroRNAs are small noncoding RNAs encoded in eukaryotic genomes that have been found to play critical roles in most biological processes, including cancer. This is true for glioblastoma, the most common and lethal primary brain tumor, for which microRNAs have been shown to strongly influence cell viability, stem cell characteristics, invasiveness, angiogenesis, metabolism, and immune evasion. Developing microRNAs as prognostic markers or as therapeutic agents is showing increasing promise and has potential to reach the clinic in the next several years. This succinct review summarizes current progress and future directions in this exciting and steadily expanding field.
Elderly Patients Benefit From Second-Line Cytotoxic Chemotherapy: A Subset Analysis of a Randomized Phase III Trial of Pemetrexed Compared With Docetaxel in Patients With Previously Treated Advanced Non–Small-Cell Lung Cancer
Authors: Glen J. Weiss, Corey Langer, Rafael Rosell, Nasser Hanna, Frances Shepherd, Lawrence H. Einhorn, Binh Nguyen, Sofia Paul, Patrick McAndrews, Paul A. Bunn, Karen Kelly
Journal: Journal of Clinical Oncology (2006)

Numerous prospective and retrospective studies have concluded that elderly patients (> or = 70 years old) achieve a similar survival benefit, with acceptable toxicity, from first-line cytotoxic chemotherapy for the treatment of advanced non-small-cell lung cancer (NSCLC) compared with their younger counterparts. However, few published data exist on the efficacy and tolerability of second-line cytotoxic therapy in this population.Retrospective analysis of a large second-line trial was performed. Data from 571 patients randomly assigned to docetaxel 75 mg/m2 or pemetrexed 500 mg/m2 every 3 weeks were analyzed for efficacy and toxicity comparisons between age groups and treatment arms.Eighty-six of 571 patients (15%) were > or = 70 years old, similar to rates of elderly observed in the first-line setting. Elderly patients receiving pemetrexed (n = 47) or docetaxel (n = 39) had a median survival of 9.5 and 7.7 months compared with 7.8 and 8.0 months for younger patients receiving pemetrexed (n = 236) or docetaxel (n = 249), respectively. Elderly patients treated with pemetrexed had a longer time to progression and a longer survival than their counterpart patients treated with docetaxel (not statistically significant). Febrile neutropenia was less frequent in elderly patients treated with pemetrexed (2.5%) compared with docetaxel (19%; P = .025), with only one death as a result of toxicity (docetaxel arm).Elderly patient participation was similar to rates observed in the first-line setting. There was no significant difference in outcome or toxicity between elderly and younger patients. For elderly patients with advanced NSCLC and good performance status, second-line cytotoxic therapy is appropriate. In this subset, pemetrexed produced a more favorable toxicity profile.
Theranostic Self-Assembly Structure of Gold Nanoparticles for NIR Photothermal Therapy and X-Ray Computed Tomography Imaging
Authors: Heng Deng, Yanqi Zhong, Meihong Du, Qinjun Liu, Zhanming Fan, Fengying Dai, Xin Zhang
Journal: Theranostics (2014)

The controllable self-assembly of amphiphilic mixed polymers grafted gold nanoparitcles (AuNPs) leads to strong interparticle plasmonic coupling, which can be tuned to the near-infrared (NIR) region for enhanced photothermal therapy (PTT).In this study, an improved thiolation method was adopted for ATRP and ROP polymer to obtain amphiphilic brushes of PMEO 2 MA-SH and PCL-SH.By anchoring PCL-SH and PMEO 2 MA-SH onto the 14 nm AuNPs, a smart hybrid building block for self-assembly was obtained.Increasing the PCL/PMEO 2 MA chain ratio from 0.8:1, 2:1 and 3:1 to 7:1, the structure of gold assemblies (GAs) was observed to transfer from vesicle to large compound micelle (LCM).Contributed to the special dense packed structure of gold nanoparticles in LCM, the absorption spectrometry of gold nanoparticles drastically red-shifted from 520 nm to 830 nm, which endowed the GAs remarkable NIR photothermal conversion ability.In addition, gold has high X-ray absorption coefficient which qualifies gold nanomaterial a potential CT contrast agent Herein, we obtain a novel gold assembly structure which can be utilized as potential photothermal therapeutic and CT contrast agents.In vitro and In vivo studies testified the excellent treatment efficacy of optimum GAs as a PTT and CT contrast agent.In vitro degradation test, MTT assay and histology study indicated that GAs was a safe, low toxic reagent with good biodegradability.Therefore, the optimum GAs with strong NIR absorption and high X-ray absorption coefficient could be used as a theranostic agent and the formation of novel gold large compound micelle might offers a new theory foundation for engineering design and synthesis of polymer grafted AuNPs for biomedical applications.
Justice department fails to mention emergency contraception after rape
Authors: Janice Hopkins Tanne
Journal: BMJ (2005)

More than 200 US medical organisations, religious leaders, women's health advocates, and groups providing advice for people who have been sexually assaulted have asked the US Department of Justice to correct its guidelines for treating people who have been raped because they fail to mention emergency contraception.

The issue is controversial with US anti-abortion groups. Emergency contraception usually prevents an egg from being released or fertilised, but it may, rarely, prevent implantation of a fertilised egg. Some anti-abortion groups believe that life begins at conception and prevention of implantation is murder.

The Department of Justice was required by law to develop the first national guidelines for caring for people who have been sexually assaulted. The 141 page guide was published …
Clonal Expansions of Cd8+ T Cells Dominate the T Cell Infiltrate in Active Multiple Sclerosis Lesions as Shown by Micromanipulation and Single Cell Polymerase Chain Reaction
Authors: Holger Babbe, Axel Roers, Ari Waisman, Hans Lassmann, Norbert Goebels, Reinhard Hohlfeld, Michael Friese, Roland Schröder, Martina Deckert, Stephan Schmidt, Rivka Ravid, Klaus Rajewsky
Journal: The Journal of Experimental Medicine (2000)

Clonal composition and T cell receptor (TCR) repertoire of CD4+ and CD8+ T cells infiltrating actively demyelinating multiple sclerosis (MS) lesions were determined with unprecedented resolution at the level of single cells. Individual CD4+ or CD8+ T cells were isolated from frozen sections of lesional tissue by micromanipulation and subjected to single target amplification of TCR-β gene rearrangements. This strategy allows the assignment of a TCR variable region (V region) sequence to the particular T cell from which it was amplified. Sequence analysis revealed that in both cases investigated, the majority of CD8+ T cells belonged to few clones. One of these clones accounted for 35% of CD8+ T cells in case 1. V region sequence comparison revealed signs of selection for common peptide specificities for some of the CD8+ T cells in case 1. In both cases, the CD4+ T cell population was more heterogeneous. Most CD4+ and CD8+ clones were represented in perivascular infiltrates as well as among parenchymal T cells. In case 2, two of the CD8+ clones identified in brain tissue were also detected in peripheral blood. Investigation of the antigenic specificities of expanded clones may help to elucidate their functional properties.
Heart Failure and Protein Quality Control
Authors: Xuejun Wang, Jeffrey Robbins
Journal: Circulation Research (2006)

The heart is constantly under mechanical, metabolic, and thermal stress, even at baseline physiological conditions, and cardiac stress may increase as a result of environmental or intrinsic pathological insults. Cardiomyocytes are continuously challenged to efficiently and properly fold nascent polypeptides, traffic them to their appropriate cellular locations, and keep them from denaturing in the face of normal and pathological stimuli. Because deployment of misfolded or unfolded proteins can be disastrous, cells, in general, and cardiomyocytes, in particular, have developed a multilayered protein quality control system for maintaining proper protein conformation and for reorganizing and removing misfolded or aggregated polypeptides. Here, we examine recent data pointing to the importance of protein quality control in cardiac homeostasis and disease.
Tachykinin-independent effects of capsaicin on smooth muscle in human isolated bronchi.
Authors: J L Ellis, J S Sham, B J Undem
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Contractile and relaxant responses to capsaicin and resiniferatoxin were examined in human isolated bronchus (5-12 mm o.d.). Bronchi isolated from 10 of 16 lungs contracted in response to capsaicin. The contractions averaged 20% of maximal contraction at 1 microM and averaged > 40% maximal contraction at 300 microM (the highest concentration studied). The capsaicin-induced contractions were mimicked by resiniferatoxin (0.1-10 microM) and inhibited by the putative capsaicin receptor antagonist, capsazepine (10 microM). The contractile response to capsaicin was not affected by the potent NK-2 selective antagonist SR 48968 (0.3 microM), whereas responses to concentrations of neurokinin A (10 nM), neurokinin B (0.1 microM), substance P (1 microM), neuropeptide gamma (10 nM), and neuropeptide K (10 nM) which produced similar-size contractions were almost abolished by 0.1 microM SR 48968. The bronchi isolated from 8 of 16 lungs also exhibited relaxations in response to capsaicin. Capsaicin-induced relaxations were not inhibited by the nitric oxide synthase inhibitor L-nitro-n-arginine (10 microM). In whole-cell patch-clamp experiments on human cultured airway smooth muscle cells, capsaicin was found to enhance outward currents due to the activation of charybdotoxin-sensitive large conductance Ca2+-activated K+ channels. Neither the capsaicin-induced contractions nor the relaxations were mimicked by angiotensin II, bombesin, or calcitonin gene-related peptide at concentrations up to 1 microM. These results suggest that capsaicin and resiniferatoxin can alter smooth muscle tone, but this response does not appear to involve substance P or related neurokinins. Relaxations to capsaicin may, however, involve the activation of large conductance Ca2+-activated K+ channels.
Lysosomal function in macromolecular homeostasis and bioenergetics in Parkinson's disease
Authors: Lonnie Schneider, Jianhua Zhang
Journal: Molecular Neurodegeneration (2010)

The pathological changes occurring in Parkinson's and several other neurodegenerative diseases are complex and poorly understood, but all clearly involve protein aggregation. Also frequently appearing in neurodegeneration is mitochondrial dysfunction which may precede, coincide or follow protein aggregation. These observations led to the concept that protein aggregation and mitochondrial dysfunction either arise from the same etiological factors or are interactive. Understanding the mechanisms and regulation of processes that lead to protein aggregation or mitochondrial dysfunction may therefore contribute to the design of better therapeutics. Clearance of protein aggregates and dysfunctional organelles is dependent on macroautophagy which is the process through which aged or damaged proteins and organelles are first degraded by the lysosome and then recycled. The macroautophagy-lysosomal pathway is essential for maintaining protein and energy homeostasis. Not surprisingly, failure of the lysosomal system has been implicated in diseases that have features of protein aggregation and mitochondrial dysfunction. This review summarizes 3 major topics: 1) the current understanding of Parkinson's disease pathogenesis in terms of accumulation of damaged proteins and reduction of cellular bioenergetics; 2) evolving insights into lysosomal function and biogenesis and the accumulating evidence that lysosomal dysfunction may cause or exacerbate Parkinsonian pathology and finally 3) the possibility that enhancing lysosomal function may provide a disease modifying therapy.