tbuckley/cabot-search huggingface dataset:
Chronic bronchitis: a 10-year follow-up
Authors: N. C. Oswald, V. C. Medvei, R. E. Waller
Journal: Thorax (1967)

A 10-year follow-up of 327 civil servants with bronchitis (301 men and 26 women) is presented. A further 14 were lost sight of during the period, so that the follow-up was 96% complete. More than one half (54%) of the men died during the 10-year period, some 57% of the deaths being attributed to respiratory causes and a further 8% to carcinoma of the bronchus. Mortality from these diseases was higher than among the general population, but other causes of death showed the normal pattern. The degree of dyspnoea noted at the first interview gave a useful estimate of prognosis, the mild, moderate, and severe groups showing progressively higher death rates. Neither the length of history nor the age at onset of symptoms could be related to mortality. The proportion of smokers among the patients was greater than expected in the general population, and although this may have been a factor contributing to the excess mortality of the group as a whole, it was not possible to determine any effect of smoking within this study.
Plans for action
Authors: Melvyn A. Goodale, A. David Milner
Journal: Behavioral and Brain Sciences (2004)

It is our contention that the concept of planning in Glover's model is too broadly defined, encompassing both action/goal selection and the programming of the constituent movements required to acquire the goal. We argue that this monolithic view of planning is untenable on neuropsychological, neurophysiological, and behavioural grounds. The evidence demands instead that a distinction be made between action planning and the specification of the initial kinematic parameters, with the former depending on processing in the ventral stream and the latter on processing in the dorsal stream.
INDUCED RESISTANCE OF THE CENTRAL NERVOUS SYSTEM TO EXPERIMENTAL INFECTION WITH EQUINE ENCEPHALOMYELITIS VIRUS
Authors: Isabel M. Morgan, R. Walter Schlesinger, Peter K. Olitsky
Journal: The Journal of Experimental Medicine (1942)

1. Neutralizing antibody to equine encephalomyelitis virus was found in the spinal fluid of rabbits sufficiently vaccinated with active or formalin-inactivated virus. Antibody was specific for the Western or for the Eastern virus. 2. Neutralizing capacity of spinal fluid was equivalent to that of a 1/300 dilution of serum of the same animal, and was of the same order of magnitude as that of perfused brain of a vaccinated animal. 3. Vaccinated rabbits which showed antibody in the spinal fluid resisted intracerebral or intracisternal injection of active virus. This immunity was specific, i.e., there was no cross-reaction between the Eastern and Western virus after vaccination with formalin-inactivated virus. On the other hand, lack of antibody in the spinal fluid, even when antibody was demonstrable in the undiluted serum, was associated with lack of cerebral resistance.
Preso1 dynamically regulates group I metabotropic glutamate receptors
Authors: Jia-Hua Hu, Linlin Yang, Paul J Kammermeier, Chester G Moore, Paul R Brakeman, Jiancheng Tu, Shouyang Yu, Ronald S Petralia, Zhe Li, Ping-Wu Zhang, Joo Min Park, Xinzhong Dong, Bo Xiao, Paul F Worley
Journal: Nature Neuroscience (2012)
A Novel Assay to Assess Primary Human Cancer Infectibility by Replication-Selective Oncolytic Adenoviruses
Authors: Yaohe Wang, Stephen Thorne, Joseph Hannock, Jennelle Francis, Tina Au, Tony Reid, Nick Lemoine, David Kirn, Gunnel Halldén
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Replication-selective oncolytic adenoviruses hold promise for cancer treatment, but the predictive use of cell lines, dissociated tumor tissue, and animal models for efficacy against primary cancers are unclear. To further evaluate cytotoxicity and the potential for efficacy of replication-competent adenoviruses we therefore developed a novel methodology using primary human cancer specimens ex vivo; ovarian, colon, rectal, and breast carcinomas were included. Experimental Design: Tissue culture conditions were developed to maintain viability of adenocarcinomas ex vivo for 48 hours postsurgery. Explants were infected by replication-competent (wild type 5 and E1A mutant dl922-947) and replication-defective (dl312) adenoviruses; early (E1A) and late (hexon) viral gene expression, αv integrins, coxsackievirus and adenovirus receptor (CAR) and tissue viability were assessed by immunohistochemistry and histopathology. Viral replication was verified by replication assays on selected samples. Results: Viral gene expression varied dramatically among cancer specimens (n = 41). With Ad5, hexon expression was high in 8 of 11 tested specimens, whereas E1A levels were detectable in 16 of 27 tumor explants. Viral gene expression, distribution, and cytopathic effects were greater postinfection with dl922-947. Specimens that supported early gene expression (E1A) also supported viral replication in 13 of 14 tested cases, determined by recovery of infectious units. As predicted, the replication-defective adenovirus dl312 was not associated with viral gene expression. Conclusions: Primary human tumor tissue remained viable when cultured ex vivo enabling evaluation of viral mutants in tissue with intact morphology. This assay may have great use in determining treatment-sensitive cancers and assess specific oncolytic mutants in individual cases.
Papilledema From Intraventricular Neurocysticercosis
Authors: Laura C. Huang, Jayanth Sridhar
Journal: JAMA Neurology (2015)

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
The molecular bases of δ/αβ T cell–mediated antigen recognition
Authors: Daniel G. Pellicci, Adam P. Uldrich, Jérôme Le Nours, Fiona Ross, Eric Chabrol, Sidonia B.G. Eckle, Renate de Boer, Ricky T. Lim, Kirsty McPherson, Gurdyal Besra, Amy R. Howell, Lorenzo Moretta, James McCluskey, Mirjam H.M. Heemskerk, Stephanie Gras, Jamie Rossjohn, Dale I. Godfrey
Journal: The Journal of Experimental Medicine (2014)

αβ and γδ T cells are disparate T cell lineages that can respond to distinct antigens (Ags) via the use of the αβ and γδ T cell Ag receptors (TCRs), respectively. Here we characterize a population of human T cells, which we term δ/αβ T cells, expressing TCRs comprised of a TCR-δ variable gene (Vδ1) fused to joining α and constant α domains, paired with an array of TCR-β chains. We demonstrate that these cells, which represent ∼50% of all Vδ1+ human T cells, can recognize peptide- and lipid-based Ags presented by human leukocyte antigen (HLA) and CD1d, respectively. Similar to type I natural killer T (NKT) cells, CD1d-lipid Ag-reactive δ/αβ T cells recognized α-galactosylceramide (α-GalCer); however, their fine specificity for other lipid Ags presented by CD1d, such as α-glucosylceramide, was distinct from type I NKT cells. Thus, δ/αβTCRs contribute new patterns of Ag specificity to the human immune system. Furthermore, we provide the molecular bases of how δ/αβTCRs bind to their targets, with the Vδ1-encoded region providing a major contribution to δ/αβTCR binding. Our findings highlight how components from αβ and γδTCR gene loci can recombine to confer Ag specificity, thus expanding our understanding of T cell biology and TCR diversity.
Effect of sildenafil on digital ulcers in systemic sclerosis: analysis from a single centre pilot study
Authors: C. S. Brueckner, M. O. Becker, T. Kroencke, D. Huscher, H. U. Scherer, M. Worm, G. Burmester, G. Riemekasten
Journal: Annals of the Rheumatic Diseases (2009)

<h3>Objective</h3> In this pilot study, the effect of sildenafil on digital ulcer (DU) healing and related clinical symptoms was analysed. <h3>Methods</h3> A total of 19 patients with systemic sclerosis (SSc) were treated with maximally tolerated sildenafil doses up to 6 months. Primary outcome was the healing of DUs. Changes in other clinical symptoms were also evaluated. <h3>Results</h3> In all, 49 DUs were present at baseline; this decreased to 17 ulcers (p&lt;0.001) at the end of sildenafil treatment. Furthermore, the visual analogue scale (VAS) score for Raynaud9s phenomenon (RP), pain and activity improved (p=0.003, p=0.002 and p=0.05, respectively). A total of 9 patients developed 12 new DUs during sildenafil treatment. <h3>Conclusions</h3> This study indicates an effect of sildenafil on DU healing in patients with SSc and an improvement of RP and associated symptoms that should be validated in controlled studies.
CoQ<sub>10</sub> Function and Role in Heart Failure and Ischemic Heart Disease
Authors: Anita Ayer, Peter Macdonald, Roland Stocker
Journal: Annual Review of Nutrition (2015)

Coenzyme Q (CoQ) is an essential lipid of cells present in all cellular compartments. The functions of CoQ in mitochondrial respiration and as an antioxidant are established, although the lipid likely has additional, presently unknown, roles. While the therapeutic utility of CoQ10 supplements is recognized in the rare cases of primary CoQ10 deficiencies, a potential role for CoQ10 supplements in cardiovascular disease, particularly heart failure, has also been studied for over 40 years. This review summarizes our current knowledge in these areas derived from animal studies and human trials. Current evidence for a benefit of CoQ10 supplements in diseases other than primary CoQ10 deficiencies is insufficient.
Enzastaurin plus temozolomide with radiation therapy in glioblastoma multiforme: A phase I study
Authors: N. Butowski, S. M. Chang, K. R. Lamborn, M. Y. Polley, R. Parvataneni, M. Hristova-Kazmierski, L. Musib, S. J. Nicol, D. E. Thornton, M. D. Prados
Journal: Neuro-Oncology (2010)

We conducted a phase I study to determine the safety and recommended phase II dose of enzastaurin (oral inhibitor of the protein kinase C-beta [PKCβ] and the PI3K/AKT pathways) when given in combination with radiation therapy (RT) plus temozolomide to patients with newly diagnosed glioblastoma multiforme or gliosarcoma. Patients with Karnofsky performance status ≥60 and no enzyme-inducing anti-epileptic drugs received RT (60 Gy) over 6 weeks, concurrently with temozolomide (75 mg/m2 daily) followed by adjuvant temozolomide (200 mg/m2) for 5 days/28-d cycle. Enzastaurin was given once daily during RT and adjuvantly with temozolomide; the starting dose of 250 mg/d was escalated to 500 mg/d if ≤1/6 patients had dose-limiting toxicity (DLT) during RT and the first adjuvant cycle. Patients continued treatment for 12 adjuvant cycles unless disease progression or unacceptable toxicity occurred. Twelve patients enrolled. There was no DLT in the first 6 patients treated with 250 mg enzastaurin. At 500 mg, 2 of 6 patients experienced a DLT (1 Grade 4 and 1 Grade 3 thrombocytopenia). The patient with Grade 3 DLT recovered to Grade <1 within 28 days and adjuvant temozolomide and enzastaurin was reinitiated with dose reductions. The other patient recovered to Grade <1 toxicity after 28 days and did not restart treatment. Enzastaurin 250 mg/d given concomitantly with RT and temozolomide and adjuvantly with temozolomide was well tolerated and is the recommended phase II dose. The proceeding phase II trial has finished accrual and results will be reported in 2009.
Cell-Permeable Peptide DEPDC1-ZNF224 Interferes with Transcriptional Repression and Oncogenicity in Bladder Cancer Cells
Authors: Yosuke Harada, Mitsugu Kanehira, Yoshiko Fujisawa, Ryo Takata, Taro Shuin, Tsuneharu Miki, Tomoaki Fujioka, Yusuke Nakamura, Toyomasa Katagiri
Journal: Cancer Research (2010)

Bladder cancer is the second most common genitourinary cancer worldwide, yet its oncogenic origins remain poorly understood. The cancer-testis antigen DEPDC1 was shown recently to contribute to bladder cancer oncogenesis. In this study, we examined the biological functions of DEPDC1 and defined a potential therapeutic strategy to target this molecule. Coimmunoprecipitation and immunocytochemistry revealed that DEPDC1 interacted and colocalized with zinc finger transcription factor ZNF224, a known transcriptional repressor. Inhibiting this interaction with a cell-permeable peptide corresponding to the ZNF224-interacting domain in DEPDC1 induced apoptosis of bladder cancer cells in vitro and in vivo. By inhibiting DEPDC1-ZNF224 complex formation, this peptide triggered transcriptional activation of A20, a potent inhibitor of the NF-kappaB signaling pathway. Our findings indicate that the DEPDC1-ZNF224 complex is likely to play a critical role in bladder carcinogenesis.
A single nucleotide polymorphism in the <i>IRF5</i> promoter region is associated with susceptibility to rheumatoid arthritis in the Japanese population
Authors: K Shimane, Y Kochi, R Yamada, Y Okada, A Suzuki, A Miyatake, M Kubo, Y Nakamura, K Yamamoto
Journal: Annals of the Rheumatic Diseases (2008)

Objectives: Interferon regulatory factor 5 (IRF5) is a member of the IRF family of transcription factors, which regulate the production of proinflammatory cytokines. Polymorphisms in the IRF5 gene have been associated with susceptibility to systemic lupus erythaematosus (SLE) in Caucasian and Asian populations, but their involvement in other autoimmune diseases is still uncertain. Here, we assessed the genetic role of IRF5 in susceptibility to rheumatoid arthritis (RA) in Japanese subjects. Methods: We selected 13 single nucleotide polymorphisms (SNPs) and a CGGGG insertion–deletion polymorphism in the IRF5 gene. We performed 2 sets of case–control comparisons using Japanese subjects (first set: 830 patients with RA and 658 controls; second set: 1112 patients with RA and 940 controls), and then performed a stratified analysis using human leukocyte antigen (HLA)-DRB1 shared epitope (SE) status. We genotyped the SNPs using TaqMan assays. Results: A significant association of the rs729302 A allele with RA susceptibility was found in both sets (odds ratio (OR) 1.22, 95% CI 1.09 to 1.35, p&lt;0.001 in the combined analysis). When the patients were stratified by the SE, the rs729302 A allele was found to confer increased risk to RA in patients that were SE negative (OR 1.50, 95% CI 1.17 to 1.92, p = 0.001) as compared with patients carrying the SE (OR 1.11, 95% CI 0.93 to 1.33, p = 0.24). In both sets, no genotyped polymorphisms were significantly associated with RA susceptibility, but rs729302 was significantly associated. Conclusions: These findings indicate that the promoter polymorphism of IRF5 is a genetic factor conferring predisposition to RA, and that it contributes considerably to disease pathogenesis in patients that were SE negative.
HHV-8 encoded LANA-1 alters the higher organization of the cell nucleus
Authors: György Stuber, Karin Mattsson, Emilie Flaberg, Emrah Kati, Laszlo Markasz, Julie A Sheldon, George Klein, Thomas F Schulz, Laszlo Szekely
Journal: Molecular Cancer (2007)

Abstract The latency-associated nuclear antigen (LANA-1) of Human Herpes Virus 8 (HHV-8), alternatively called Kaposi Sarcoma Herpes Virus (KSHV) is constitutively expressed in all HHV-8 infected cells. LANA-1 accumulates in well-defined foci that co-localize with the viral episomes. We have previously shown that these foci are tightly associated with the borders of heterochromatin [1]. We have also shown that exogenously expressed LANA-1 causes an extensive re-organization of Hoechst 33248 DNA staining patterns of the nuclei in non-HHV-8 infected cells [2]. Here we show that this effect includes the release of the bulk of DNA from heterochromatic areas, in both human and mouse cells, without affecting the overall levels of heterochromatin associated histone H3 lysine 9 tri-methylation (3MK9H3). The release of DNA from the heterochromatic chromocenters in LANA-1 transfected mouse cells co-incides with the dispersion of the chromocenter associated methylcytosin binding protein 2 (MECP2). The localization of 3MK9H3 to the remnants of the chromocenters remains unaltered. Moreover, exogeneously expressed LANA-1 leads to the relocation of the chromocenters to the nuclear periphery, indicating extensive changes in the positioning of the chromosomal domains in the LANA-1 harboring interphase nucleus. Using a series of deletion mutants we have shown that the chromatin rearranging effects of LANA-1 require the presence of a short (57 amino acid) region that is located immediately upstream of the internal acidic repeats. This sequence lies within the previously mapped binding site to histone methyltransferase SUV39H1. We suggest that the highly concentrated LANA-1, anchored to the host genome in the nuclear foci of latently infected cells and replicated through each cell generation, may function as "epigenetic modifier". The induction of histone modification in adjacent host genes may lead to altered gene expression, thereby contributing to the viral oncogenesis.
CD4+ regulatory T cells require CTLA-4 for the maintenance of systemic tolerance
Authors: Randall H. Friedline, David S. Brown, Hai Nguyen, Hardy Kornfeld, JinHee Lee, Yi Zhang, Mark Appleby, Sandy D. Der, Joonsoo Kang, Cynthia A. Chambers
Journal: The Journal of Experimental Medicine (2009)

Cytotoxic T lymphocyte antigen-4 (CTLA-4) plays a critical role in negatively regulating T cell responses and has also been implicated in the development and function of natural FOXP3+ regulatory T cells. CTLA-4–deficient mice develop fatal, early onset lymphoproliferative disease. However, chimeric mice containing both CTLA-4–deficient and –sufficient bone marrow (BM)–derived cells do not develop disease, indicating that CTLA-4 can act in trans to maintain T cell self-tolerance. Using genetically mixed blastocyst and BM chimaeras as well as in vivo T cell transfer systems, we demonstrate that in vivo regulation of Ctla4−/− T cells in trans by CTLA-4–sufficient T cells is a reversible process that requires the persistent presence of FOXP3+ regulatory T cells with a diverse TCR repertoire. Based on gene expression studies, the regulatory T cells do not appear to act directly on T cells, suggesting they may instead modulate the stimulatory activities of antigen-presenting cells. These results demonstrate that CTLA-4 is absolutely required for FOXP3+ regulatory T cell function in vivo.
The expression of the interleukin 6 gene is induced by the human immunodeficiency virus 1 TAT protein.
Authors: G Scala, M R Ruocco, C Ambrosino, M Mallardo, V Giordano, F Baldassarre, E Dragonetti, I Quinto, S Venuta
Journal: The Journal of Experimental Medicine (1994)

Human immunodeficiency virus 1 (HIV1) infection is associated with severe psoriasis, B cell lymphoma, and Kaposi's sarcoma. A deregulated production of interleukin 6 (IL-6) has been implicated in the pathogenesis of these diseases. The molecular mechanisms underlying the abnormal IL-6 secretion of HIV1-infected cells may include transactivation of the IL-6 gene by HIV1. To test this hypothesis, we used the pIL6Pr-chloramphenicol acetyltransferase (CAT) plasmid, an IL-6 promoter-CAT construct, as a target of the transactivating function of the HIV1 TAT protein. By cotransfecting the pIL6Pr-CAT and the tat-expressing pSVT8 plasmid in MC3 B-lymphoblastoid or in HeLa epithelial cells, we observed that TAT transactivates the human IL-6 promoter. These results were confirmed when pIL6Pr-CAT was transfected in MC3 or HeLa cells that constitutively expressed the tat gene in a sense (pSVT8 cells) or antisense (pSVT10 cells) orientation. 5' deletion plasmids of pIL6Pr-CAT, in which regions at -658, -287, and -172 were inserted 5' to the cat gene, were transiently transfected in pSVT10 and pSVT8 cells and showed that TAT-induced activation of the IL-6 promoter required a minimal region located between -287 and -54 bp. Moreover, experiments with plasmids carrying the -658, -287, and -172 bp regions of the IL-6 promoter inserted downstream to a TAR-deleted HIV1-LTR identified the sequence of -172 to -54 as the minimal region of the IL-6 promoter required for TAT to transactivate the TAR-deleted HIV1-LTR. By DNA-protein binding experiments, tat-transfected cells expressed a consistent increase in kappa B and nuclear factor (NF)-IL-6 binding activity. Accordingly, the pDRCAT and IL-1REK9CAT, carrying tandem repeats of NF-kappa B or NF-IL6 binding motifs, respectively, were activated in TAT-expressing cells. The biological relevance of the TAT-induced IL-6 secretion was addressed by generating 7TD1 cells, an IL-6-dependent mouse cell line, stably expressing the tat gene. These tat-positive cells expressed the endogenous IL-6 gene, secreted high amounts of murine IL-6, and grew efficiently in the absence of exogenous IL-6. Moreover, the tat-positive 7TD1 cells sustained the growth of parental 7TD1 cells and showed a dramatic increase in their tumorigenic potency. These results suggest that TAT protein may play a role in the pathogenesis of some HIV1-associated diseases by modulating the expression of host cellular genes.
Kupffer cells are activated in cirrhotic portal hypertension and not normalised by TIPS
Authors: P. Holland-Fischer, H. Gronbaek, T. D. Sandahl, S. K. Moestrup, O. Riggio, L. Ridola, N. K. Aagaard, H. J. Moller, H. Vilstrup
Journal: Gut (2011)

<h3>Introduction</h3> Hepatic macrophages (Kupffer cells) undergo inflammatory activation during the development of portal hypertension in experimental cirrhosis; this activation may play a pathogenic role or be an epiphenomenon. Our objective was to study serum soluble CD163 (sCD163), a sensitive marker of macrophage activation, before and after reduction of portal venous pressure gradient by insertion of a transjugular intrahepatic portosystemic shunt (TIPS) in patients with cirrhosis. <h3>Methods</h3> sCD163 was measured in 11 controls and 36 patients before and 1, 4 and 26 weeks after TIPS. We used lipopolysaccharide binding protein (LBP) levels as a marker of endotoxinaemia. Liver function and clinical status of the patients were assessed by galactose elimination capacity and Model for End Stage Liver Disease score. <h3>Results</h3> The sCD163 concentration was more than threefold higher in the patients than in the controls (median 5.22 mg/l vs 1.45 mg/l, p&lt;0.001). The sCD163 was linearly related to the portal venous pressure gradient (r<sup>2</sup>=0.24, p&lt;0.001), also after adjustment for cirrhosis status. The sCD163 concentration was 12% higher in the hepatic than in the portal vein (p&lt;0.02). The LBP level was 70% higher in the patients (52.2 vs 30.4 μg/l, p&lt;0.001). During follow-up after TIPS, the sCD163 concentration did not change while LBP almost normalised. <h3>Conclusion</h3> Kupffer cells were activated in patients with liver cirrhosis in parallel with their portal hypertension. The activation was not alleviated by the mechanical reduction of portal hypertension and the decreasing signs of endotoxinaemia. The findings suggest that Kupffer cell activation is a constitutive event that may play a pathogenic role for portal hypertension.