tbuckley/cabot-search huggingface dataset:
Heat Shock Protein 70 Confers Cardiovascular Protection During Endotoxemia via Inhibition of Nuclear Factor-κB Activation and Inducible Nitric Oxide Synthase Expression in the Rostral Ventrolateral Medulla
Authors: Julie Y.H. Chan, Chen-Chun Ou, Ling-Lin Wang, Samuel H.H. Chan
Journal: Circulation (2004)

Overproduction of nitric oxide (NO) by inducible NO synthase (iNOS) in the rostral ventrolateral medulla (RVLM), where sympathetic premotor neurons are located, plays a pivotal role in the manifestation of fatal cardiovascular depression during endotoxemia. The iNOS gene is regulated transcriptionally by nuclear factor-kappaB (NF-kappaB) activation. The present study tested the hypothesis that heat shock protein 70 (HSP70) may confer protection against sepsis-induced circulatory fatality via inhibition of iNOS gene expression in the RVLM through prevention of NF-kappaB activation.Adult male Sprague-Dawley rats subjected to a brief hyperthermic heat shock (42 degrees C for 15 minutes) exhibited significant upregulation of HSP70 in the RVLM. Brief heat shock preconditioning also significantly suppressed iNOS mRNA or protein surge and alleviated hypotension, bradycardia, and reduction in neurogenic sympathetic vasomotor activity manifested during experimental endotoxemia induced by intravenous administration of Escherichia coli lipopolysaccharide. An increase in DNA binding activity and nuclear translocation of transcription factor NF-kappaB were detected during endotoxemia. Heat shock preconditioning significantly decreased DNA binding activity of NF-kappaB, which was reversed by microinjection of an hsp70 antisense oligonucleotide bilaterally into the RVLM. Heat shock preconditioning also blocked inhibitory kappaB (IkappaB) kinase activity or degradation of IkappaB in the RVLM during endotoxemia.We conclude that HSP70 confers protection against sepsis-related circulatory fatality via inhibition of iNOS gene expression in the RVLM through prevention of NF-kappaB activation in cellular processes that include prevention of IkappaB kinase activation and inhibition of IkappaBalpha degradation.
Longitudinal Analysis of Depressive Symptoms and Glycemic Control in Type 2 Diabetes
Authors: James E. Aikens, Denise White Perkins, Bonnie Lipton, John D. Piette
Journal: Diabetes Care (2009)

OBJECTIVE To compare whether depressive symptoms are more strongly related to subsequent or prior glycemic control in type 2 diabetes and to test whether patient characteristics modify these longitudinal associations. RESEARCH DESIGN AND METHODS On two occasions separated by 6 months, depressive symptoms and glycemic control were assessed in 253 adults with type 2 diabetes. Regression analyses examined depressive symptoms as both a predictor and outcome of glycemic control and tested whether medication regimen (e.g., insulin versus oral drugs) was an effect modifier before and after adjusting for baseline levels of the outcome being predicted. RESULTS Depressive symptom severity predicted poor glycemic control 6 months later (P = 0.018) but not after baseline glycemic control was taken into account (P = 0.361). Although baseline glycemic control did not generally predict depressive symptoms 6 months later (P = 0.558), it significantly interacted with regimen (P = 0.008). Specifically, glycemic control predicted depressive symptoms among patients prescribed insulin (β = 0.31, P = 0.002) but not among those prescribed oral medication alone (β = −0.10, P = 0.210). Classifying depression dichotomously produced similar but weaker findings. CONCLUSIONS Depressive symptoms do not necessarily lead to worsened glycemic control. In contrast, insulin-treated patients in poor glycemic control are at moderate risk for worsening of depressive symptoms. These patients should be carefully monitored to determine whether depression treatment should be initiated or intensified.
OV6+ tumor-initiating cells contribute to tumor progression and invasion in human hepatocellular carcinoma
Authors: Wen Yang, Chao Wang, Yan Lin, Qiong Liu, Le-xing Yu, Liang Tang, He-Xin Yan, Jing Fu, Yao Chen, Hui-Lu Zhang, Liang Tang, Long-Yi Zheng, Ya-Qin He, Yu-Qiong Li, Fu-Quan Wu, Shan-Shan Zou, Zhong Li, Meng-Chao Wu, Gen-Sheng Feng, Hong-Yang Wang
Journal: Journal of Hepatology (2012)
T and B cells that recognize the same antigen do not transcribe similar heavy chain variable region gene segments.
Authors: E Kraig, M Kronenberg, J A Kapp, C W Pierce, A F Abruzzini, C M Sorensen, L E Samelson, R H Schwartz, L E Hood
Journal: The Journal of Experimental Medicine (1983)

We have attempted to determine whether T cells and B cells that have the same antigenic specificity and whose receptors share idiotypic determinants in fact express similar VH gene segments. To do this, we have obtained and characterized a cDNA clone containing the entire coding sequence for the VH gene from a glutamic acid60/alanine30/tyrosine10 (GAT)-binding immunoglobulin that carries the CGAT idiotype. The GAT-VH clone was hybridized to Northern blots of GAT-specific T cell RNAs; there was no evidence of a T cell transcript that hybridized to the GAT-VH probe. The T cells analyzed included: (a) 10 GAT-binding suppressor T cell hybridomas, 6 of which secreted factors with CGAT idiotypic determinants, (b) one GAT-specific helper T cell hybridoma, and (c) two GAT-specific helper T cell lines grown in the absence of feeder cells. The detection limit of the Northern blot analysis was 1-2 copies of a particular mRNA species per cell for the hybridomas and 5-10 copies per cell for the T cell lines. Therefore, we conclude that T and B lymphocytes responding to GAT do not utilize similar VH gene segments. Furthermore, the presence of idiotypic determinants on T lymphocytes does not necessarily imply close structural similarity between T and B cell antigen receptors.
MTHFR Gene Polymorphism as a Risk Factor for Diabetic Retinopathy in Type 2 Diabetic Patients Without Serum Creatinine Elevation
Authors: Makiko Maeda, Isamu Yamamoto, Masakatsu Fukuda, Mari Nishida, Junko Fujitsu, Shinpei Nonen, Tsuyoshi Igarashi, Takashi Motomura, Makiko Inaba, Yasushi Fujio, Junichi Azuma
Journal: Diabetes Care (2003)

Diabetic retinopathy (DR), a serious microangiopathic complication of diabetes, is the leading cause of catastrophic loss of vision in Japan. Methylenetetrahydrofolate reductase (MTHFR) is an enzyme involved in remethylation of homocysteine to methionine. A point mutation (C677T) in the MTHFR gene leads to impaired activity and is the most common genetic determinant of moderate hyperhomocysteinemia in the general population (1). Neugebauer et al. (2) reported a significantly higher prevalence of the mutant allele in diabetic patients with retinopathy. However, in their study, patients with retinopathy showed severe renal failure with higher levels of serum creatinine compared with those without retinopathy. Considering …
Perirhinal cortex and hippocampus mediate parallel processing of object and spatial location information
Authors: Raymond P. Kesner
Journal: Behavioral and Brain Sciences (1999)

An alternative to Aggleton &amp; Brown's interpretation is presented suggesting that the perirhinal cortex and hippocampus mediate different attribute information, but use the same processes, supporting the idea of parallel processing based on attribute (visual object and spatial location) rather than process characteristics (item recognition and familiarity).
Identification of the B-Raf/Mek/Erk MAP kinase pathway as a target for all-trans retinoic acid during skin cancer promotion
Authors: Satish B Cheepala, Weihong Yin, Zanobia Syed, Jennifer N Gill, Alaina McMillian, Heather E Kleiner, Mark Lynch, Rasiah Loganantharaj, Marjan Trutschl, Urska Cvek, John L Clifford
Journal: Molecular Cancer (2009)

Abstract Background Retinoids have been studied extensively for their potential as therapeutic and chemopreventive agents for a variety of cancers, including nonmelanoma skin cancer (NMSC). Despite their use for many years, the mechanism of action of retinoids in the prevention of NMSC is still unclear. In this study we have attempted to understand the chemopreventive mechanism of all- trans retinoic acid (ATRA), a primary biologically active retinoid, in order to more efficiently utilize retinoids in the clinic. Results We have used the 2-stage dimethylbenzanthracene (DMBA)/12- O -tetradecanoylphorbol-13-acetate (TPA) mouse skin carcinogenesis model to investigate the chemopreventive effects of ATRA. We have compared the gene expression profiles of control skin to skin subjected to the 2-stage protocol, with or without ATRA, using Affymetrix 430 2.0 DNA microarrays. Approximately 49% of the genes showing altered expression with TPA treatment are conversely affected when ATRA is co-administered. The activity of these genes, which we refer to as 'counter-regulated', may contribute to chemoprevention by ATRA. The counter-regulated genes have been clustered into functional categories and bioinformatic analysis has identified the B-Raf/Mek/Erk branch of the MAP kinase pathway as one containing several genes whose upregulation by TPA is blocked by ATRA. We also show that ATRA blocks signaling through this pathway, as revealed by immunohistochemistry and Western blotting. Finally, we found that blocking the B-Raf/Mek/Erk pathway with a pharmacological inhibitor, Sorafenib (BAY43-9006), induces squamous differentiation of existing skin SCCs formed in the 2-stage model. Conclusion These results indicate that ATRA targets the B-Raf/Mek/Erk signaling pathway in the 2-stage mouse skin carcinogenesis model and this activity coincides with its chemopreventive action. This demonstrates the potential for targeting the B-Raf/Mek/Erk pathway for chemoprevention and therapy of skin SCC in humans. In addition our DNA microarray results provide the first expression signature for the chemopreventive effect of ATRA in a mouse skin cancer model. This is a potential source for novel targets for ATRA and other chemopreventive and therapeutic agents that can eventually be tested in the clinic.
Serogroup A meningococcal conjugate vaccination in Burkina Faso: analysis of national surveillance data
Authors: Ryan T Novak, Jean Ludovic Kambou, Fabien VK Diomandé, Tiga F Tarbangdo, Rasmata Ouédraogo-Traoré, Lassana Sangaré, Clement Lingani, Stacey W Martin, Cynthia Hatcher, Leonard W Mayer, F Marc LaForce, Fenella Avokey, Mamoudou H Djingarey, Nancy E Messonnier, Sylvestre R Tiendrébéogo, Thomas A Clark
Journal: The Lancet Infectious Diseases (2012)
Hemodynamic Performance of a Transplanted Human Heart
Authors: RICHARD A. CARLETON, STANLEY J. HELLER, HASSAN NAJAFI, JAMES G. CLARK
Journal: Circulation (1969)

Cardiac catheterization studies, performed 3 weeks after cardiac homotransplantation, revealed nearly normal cardiac performance. Alteration in heart rate by right atrial pacing, passive elevation of the legs, and exercise modified cardiac performance predominantly by variation in ventricular filling. Isoproterenol infusion increased stroke volume above the level predicted from the ventricular end-diastolic pressure. The heart was hypersensitive to beta-adrenergic stimulation with isoproterenol as judged by a greater responsiveness of the donor sinus node than the recipient sinus node, by prolongation of ventricular filling time, and by shortening the P-R interval for any given paced heart rate. These measures permitted tests for endogenous catecholamine effects during passive leg elevation and during exercise. Only after the 3 minutes of exercise was a small beta-adrenergic effect detectable. These data demonstrate the dependence of the denervated human heart upon variation in ventricular filling as the predominant mode of regulation of cardiac performance.
ACE-inhibition promotes apoptosis after balloon injury of rat carotid arteries
Authors: A Holm
Journal: Cardiovascular Research (2000)

Objective: Angiotensin II stimulates vascular smooth muscle cell (VSMC) growth, and is considered to be an important mediator of intimal thickening after vascular injury. Recent evidence has indicated that VSMC apoptosis plays a major role in the response to balloon injury, and we therefore examined the effect of angiotensin converting enzyme (ACE)-inhibition on VSMC apoptosis and vascular lesion formation in the rat model of balloon injury. Methods: Male Sprague–Dawley rats were subjected to carotid artery balloon injury and randomised to a standard diet or a diet supplemented with 1 mg/ml captopril in the drinking water. Animals were sacrificed 2 and 14 days after injury for assessment of apoptosis and proliferation by in situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling (TUNEL) and proliferating cell nuclear antigen (PCNA) immunohistochemistry, respectively. At 14 days post injury, vessel cross-sections were subjected to microscopic morphometry and total cell numbers were determined. Results: At 2 days after balloon injury, captopril-treated animals displayed a significant increase in the percentage of TUNEL-positive VSMCs in the medial area (12±4% vs. 1±1%; P<0.05) as compared to controls. This increase in early apoptosis was associated with decreased intimal cellularity 14 days post injury (238±47 cells/cross-section vs. 449±75 cells/cross-section; P<0.05), and a reduction of neointimal formation (0.13±0.02 mm2 vs. 0.23±0.04 mm2; P<0.05). The fraction of PCNA-positive VSMCs per cross-section 2 or 14 days after injury was not significantly altered by captopril administration. Conclusion: Captopril inhibits neointimal formation in the rat model of arterial injury by mechanisms involving induction of VSMC apoptosis.
Immunologic Evaluation of Personalized Peptide Vaccination for Patients with Advanced Malignant Glioma
Authors: Naoki Yajima, Ryuya Yamanaka, Takashi Mine, Naoto Tsuchiya, Jumpei Homma, Masakazu Sano, Terukazu Kuramoto, Yayoi Obata, Nobukazu Komatsu, Yoshimi Arima, Akira Yamada, Minoru Shigemori, Kyogo Itoh, Ryuichi Tanaka
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The primary goal of this phase I study was to assess the safety and immunologic responses of personalized peptide vaccination for patients with advanced malignant glioma. Experimental Design: Twenty-five patients with advanced malignant glioma (8 grade 3 and 17 grade 4 gliomas) were evaluated in a phase I clinical study of a personalized peptide vaccination. For personalized peptide vaccination, prevaccination peripheral blood mononuclear cells and plasma were provided to examine cellular and humoral responses to 25 or 23 peptides in HLA-A24+ or HLA-A2+ patients, respectively; then, only the reactive peptides (maximum of four) were used for in vivo administration. Results: The protocols were well tolerated with local redness and swelling at the injection site in most cases. Twenty-one patients received more than six vaccinations and were evaluated for both immunologic and clinical responses. Increases in cellular or humoral responses specific to at least one of the vaccinated peptides were observed in the postvaccination (sixth) samples from 14 or 11 of 21 patients, respectively. More importantly, significant levels of peptide-specific IgG were detected in the postvaccination tumor cavity or spinal fluid of all of the tested patients who showed favorable clinical responses. Clinical responses were 5 partial responses, 8 cases of stable disease, and 8 cases of progressive disease. The median overall survival for patients with recurrent glioblastoma multiforme in this study (n = 17) was 622 days. Conclusions: Personalized peptide vaccinations were recommended for the further clinical study to malignant glioma patients.
Importance of Multiagent Chemotherapy Regimens in Ovarian Carcinoma: Dose Intensity Analysis
Authors: L. Levin, R. Simon, W. Hryniuk
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Importance of Multiagent Chemotherapy Regimens in Ovarian Carcinoma: Dose Intensity Analysis Get access Leslie Levin, Leslie Levin Department of Oncology, Faculty of Medicine, University of Western Ontario and London Regional Cancer CenterLondon, Ont., Canada Correspondence to : Leslie Levin, M.D., London Regional Cancer Center, 790 Commissioners Rd. East, London, ON, Canada N6A 4L6 Search for other works by this author on: Oxford Academic PubMed Google Scholar Richard Simon, Richard Simon Biometric Research Branch, Division of Cancer Treatment, National Cancer InstituteBethesda, Md Search for other works by this author on: Oxford Academic PubMed Google Scholar William Hryniuk William Hryniuk University of California at San Diego Cancer Center, San DiegoCalif * See "Notes" section following "References". Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 21, 3 November 1993, Pages 1732–1742, https://doi.org/10.1093/jnci/85.21.1732 Published: 03 November 1993 Article history Received: 26 April 1993 Revision received: 27 July 1993 Accepted: 03 August 1993 Published: 03 November 1993
The first minutes of reperfusion: a window of opportunity for cardioprotection
Authors: H Piper
Journal: Cardiovascular Research (2004)

During the past decade, the understanding has grown that control of the conditions of reperfusion is critical for salvaging ischemic-reperfused myocardium. The first few minutes of reperfusion constitute a critical phase, as here lethal tissue injury in addition to that already developed during ischemia may be initiated. The identification of the mechanisms of reperfusion-induced cell death opens a new window of opportunity for cardioprotection in the clinic. Development of cardiomyocyte hypercontracture is a predominant feature of reperfusion injury. We and others have shown that control of hypercontracture in reperfusion reduces the extent of tissue injury. On the cellular level, it was shown that reperfusion-induced hypercontracture might either originate from a rigor-type mechanism, when energy recovery proceeds very slowly, or from Ca2+ overload, when energy recovery is rapid but cytosolic Ca2+ load is high. These two mechanisms can be influenced by various interventions that either connect with cytosolic Ca2+ control or myofibrillar Ca2+ sensitivity or with mitochondrial energy production. These experimental approaches will hopefully lead to novel strategies for clinical cardioprotection during the early phase of reperfusion.
Schizophrenia: New Pathological Insights and Therapies
Authors: L. Fredrik Jarskog, Seiya Miyamoto, Jeffrey A. Lieberman
Journal: Annual Review of Medicine (2007)

The neurodevelopmental hypothesis of schizophrenia posits an interaction between multiple susceptibility genes and one or more environmental insults in early life, resulting in altered brain development and the emergence of psychosis in early adulthood. Based on this framework, it has been argued that most neuropathological deficits observed in post mortem and neuroimaging studies of schizophrenia represent one or more lesions that originated in early life and remained static thereafter. However, recent longitudinal neuroimaging studies demonstrate a progressive component to the neuropathology of new-onset schizophrenia. This opens the possibility that the functional decline seen in many patients following the onset of illness may be halted or slowed. This review provides an update on developments in research on the neuropathology of schizophrenia and discusses recent advances in antipsychotic treatment and the potential impact on long-term outcomes.
Comparative analysis of tandem repeats from hundreds of species reveals unique insights into centromere evolution
Authors: Daniël P. Melters, Keith R. Bradnam, Hugh A. Young, Natalie Telis, Michael R. May, J. Graham Ruby, Robert Sebra, Paul Peluso, John Eid, David Rank, José Fernando Garcia, Joseph L. DeRisi, Timothy Smith, Christian Tobias, Jeffrey Ross-Ibarra, Ian F. Korf, Simon W. L. Chan
Journal: Genome biology (2013)

Abstract Background Centromeres are essential for chromosome segregation, yet their DNA sequences evolve rapidly. In most animals and plants that have been studied, centromeres contain megabase-scale arrays of tandem repeats. Despite their importance, very little is known about the degree to which centromere tandem repeats share common properties between different species across different phyla. We used bioinformatic methods to identify high-copy tandem repeats from 282 species using publicly available genomic sequence and our own data. Results Our methods are compatible with all current sequencing technologies. Long Pacific Biosciences sequence reads allowed us to find tandem repeat monomers up to 1,419 bp. We assumed that the most abundant tandem repeat is the centromere DNA, which was true for most species whose centromeres have been previously characterized, suggesting this is a general property of genomes. High-copy centromere tandem repeats were found in almost all animal and plant genomes, but repeat monomers were highly variable in sequence composition and length. Furthermore, phylogenetic analysis of sequence homology showed little evidence of sequence conservation beyond approximately 50 million years of divergence. We find that despite an overall lack of sequence conservation, centromere tandem repeats from diverse species showed similar modes of evolution. Conclusions While centromere position in most eukaryotes is epigenetically determined, our results indicate that tandem repeats are highly prevalent at centromeres of both animal and plant genomes. This suggests a functional role for such repeats, perhaps in promoting concerted evolution of centromere DNA across chromosomes.
American Medicine Is on the Right Track
Authors: Henry M. Greenberg
Journal: JAMA (1998)

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