tbuckley/cabot-search huggingface dataset:
Sustained-Release Diltiazem Reduces Myocardial Ischemic Episodes in End-Stage Renal Disease
Authors: Gennaro Cice, Attilio Di Benedetto, Antonello D’Andrea, Salvatore D’Isa, Luigi Ferrara, Pina Elvira Russo, Aldo Iacono, Raffaele Calabrò
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. End-stage renal disease (ESRD) patients receiving maintenance hemodialysis and suffering from coronary artery disease (CAD) often receive doses of calcium channel antagonists that are too low. This may be the result of physician's desire to avoid adverse side effects during hemodialysis. The aim of this study was the assessment of the safety and efficacy of incremental doses of diltiazem for the treatment of myocardial ischemia in ERSD patients with CAD to identify the optimal dose of the drug. A total of 196 chronic hemodialysis patients were enrolled with CAD showing more than 5 min of transient myocardial ischemia during a 48-h Holter ECG monitoring. A double-blind, randomized, crossover, placebo-controlled trial design was used. Incremental doses of diltiazem (120 to 240 mg/d) were administered in 4 mo. With a dose of 120 and 180 mg/d, a significant reduction in the number and duration of total and symptomatic ischemic episodes was observed (P < 0.001), but the number and the duration of silent ischemic episodes were not reduced. Conversely, the efficacy on silent myocardial ischemia was obtained with a dosage of diltiazem of 240 mg/d (P < 0.001). In addition, with a sustained-release formulation (120 mg twice daily), the efficacy was similar to that obtained with four 60-mg tablets, but the safety was improved, especially during hemodialytic session. The circadian variations analysis of transient ischemic episodes showed a significant reduction in both ischemic peaks observed at baseline only with 240 mg/d of diltiazem. The findings emphasize that sustained-release diltiazem (120 mg twice daily) can be largely useful in uremic patients with CAD on maintenance dialysis. Diltiazem reduces the number and the duration of silent ischemic episodes, has a good tolerability, and positively modifies the circadian pattern of ischemic episodes. E-mail: [email protected]
Cognitive Function and the Risk for Diabetes Among Young Men
Authors: Gilad Twig, Israel Gluzman, Amir Tirosh, Hertzel C. Gerstein, Gal Yaniv, Arnon Afek, Estela Derazne, Dorit Tzur, Avraham Karasik, Barak Gordon, Eyal Fruchter, Gadi Lubin, Assaf Rudich, Tali Cukierman-Yaffe
Journal: Diabetes Care (2014)

OBJECTIVE Diabetes is a risk factor for an accelerated rate of cognitive decline and dementia. However, the relationship between cognitive function and the subsequent development of diabetes is unclear. RESEARCH DESIGN AND METHODS We conducted a historical-prospective cohort study merging data collected at premilitary recruitment assessment with information collected at the Staff Periodic Examination Center of the Israeli Army Medical Corps. Included were men aged 25 years or older without a history of diabetes at the beginning of follow-up with available data regarding their general intelligence score (GIS), a comprehensive measure of cognitive function, at age 17 years. RESULTS Among 35,500 men followed for a median of 5.5 years, 770 new cases of diabetes were diagnosed. After adjustment for age, participants in the lowest GIS category had a 2.6-fold greater risk for developing diabetes compared with those in the highest GIS category. In multivariable analysis adjusted for age, BMI, fasting plasma glucose, sociogenetic variables, and lifestyle risk factors, those in the lowest GIS category had a twofold greater risk for incident diabetes when compared with the highest GIS category (hazard ratio 2.1 [95% CI 1.5–3.1]; P &amp;lt; 0.001). Additionally, participants in the lowest GIS category developed diabetes at a mean age of 39.5 ± 4.7 years and those in the highest GIS group at a mean age of 41.5 ± 5.1 years (P for comparison 0.042). CONCLUSIONS This study demonstrates that in addition to a potential causal link between diabetes and enhanced cognitive decline, lower cognitive function at late adolescence is independently associated with an elevated risk for future diabetes.
Safety of the RTS,S/AS02D candidate malaria vaccine in infants living in a highly endemic area of Mozambique: a double blind randomised controlled phase I/IIb trial
Authors: John J Aponte, Pedro Aide, Montse Renom, Inacio Mandomando, Quique Bassat, Jahit Sacarlal, M Nelia Manaca, Sarah Lafuente, Arnoldo Barbosa, Amanda Leach, Marc Lievens, Johan Vekemans, Betuel Sigauque, Marie-Claude Dubois, Marie-Ange Demoitié, Marla Sillman, Barbara Savarese, John G McNeil, Eusebio Macete, W Ripley Ballou, Joe Cohen, Pedro L Alonso
Journal: The Lancet (2007)
Critical role for Gimap5 in the survival of mouse hematopoietic stem and progenitor cells
Authors: Yuhong Chen, Mei Yu, Xuezhi Dai, Mark Zogg, Renren Wen, Hartmut Weiler, Demin Wang
Journal: The Journal of Experimental Medicine (2011)

Mice and rats lacking the guanosine nucleotide-binding protein Gimap5 exhibit peripheral T cell lymphopenia, and Gimap5 can bind to Bcl-2. We show that Gimap5-deficient mice showed progressive multilineage failure of bone marrow and hematopoiesis. Compared with wild-type counterparts, Gimap5-deficient mice contained more hematopoietic stem cells (HSCs) but fewer lineage-committed hematopoietic progenitors. The reduction of progenitors and differentiated cells in Gimap5-deficient mice resulted in a loss of HSC quiescence. Gimap5-deficient HSCs and progenitors underwent more apoptosis and exhibited defective long-term repopulation capacity. Absence of Gimap5 disrupted interaction between Mcl-1—which is essential for HSC survival—and HSC70, enhanced Mcl-1 degradation, and compromised mitochondrial integrity in progenitor cells. Thus, Gimap5 is an important stabilizer of mouse hematopoietic progenitor cell survival.
DEFECTIVE GLUCOSE HOMEOSTASIS DURING INFECTION
Authors: Owen P. McGuinness
Journal: Annual Review of Nutrition (2005)

Infection leads to profound alterations in whole-body metabolism, which is characterized by marked acceleration of glucose, fat and protein, and amino acid flux. One of the complications of infection, especially in the nutritionally supported setting, is hyperglycemia. The hyperglycemia is caused by peripheral insulin resistance and alterations in hepatic glucose metabolism. The defects in hepatic glucose metabolism include overproduction of glucose and a failure of the liver to appropriately adapt when nutritional support is administered. Investigators have suggested that multiple factors contribute to the observed defects. In this review, I focus primarily on alterations in carbohydrate metabolism, examining both the metabolic response to infection and inflammatory stress, the role of the accompanying neuroendocrine and inflammatory responses in the metabolic response, and the interaction between the endocrine response to infection and nutritional support.
Eponyms and acronyms
Authors: T. O CHENG
Journal: Cardiovascular Research (1993)

Journal Article Eponyms and acronyms Get access TSUNG O CHENG TSUNG O CHENG Professor of Medicine George Washington University Washington DC, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 27, Issue 5, May 1993, Pages 890–891, https://doi.org/10.1093/cvr/27.5.890 Published: 01 May 1993
Optimising a curriculum for clinical haematology and biochemistry in sports medicine: a Delphi approach
Authors: K E Fallon, A C Trevitt
Journal: British Journal of Sports Medicine (2006)

To investigate issues of curriculum in the context of a postgraduate sports medicine training programme, specifically in the field of clinical biochemistry and haematology.Following the Delphi methodology, a series of sequential questionnaires was administered to curriculum developers, clinical teachers, examiners, and registrars.Agreement on a core syllabus for this subject with an indication of the core aims and objectives of teaching and learning in this field and the associated required skills and competencies. An indication of current and ideal teaching and learning methods and reasons for these preferences. A consensus of key features of a teaching module for this field and of appropriate methods of examination.The data derived from this study, as well as the experience of engaging in it, will better inform curriculum developers, teachers, and students of one another's perceptions as to what is important in and appropriate to teaching and learning in this field of sports medicine. Engagement in the exercise and broader consideration of the outcomes by those who develop the curriculum, teach, and formulate the examination process will facilitate attainment of the ideal of well aligned teaching, learning, and examination in this specific field.
Risk Index and Thrombolytic Treatment in Acute Ischemic Stroke
Authors: Neal E. Little
Journal: JAMA Neurology (2014)

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
Feasibility and Efficacy of Molecular Analysis-Directed Individualized Therapy in Advanced Non–Small-Cell Lung Cancer
Authors: George Simon, Anupama Sharma, Xueli Li, Todd Hazelton, Frank Walsh, Charles Williams, Alberto Chiappori, Eric Haura, Tawee Tanvetyanon, Scott Antonia, Alan Cantor, Gerold Bepler
Journal: Journal of Clinical Oncology (2007)

Purpose The treatment of patients with advanced non–small-cell lung cancer (NSCLC) is based on clinical trials experience. Molecular characteristics that impact metabolism and efficacy of chemotherapeutic agents are not used for decision making. Ribonucleotide reductase subunit 1 (RRM1) is crucial for nucleotide metabolism, and it is the dominant molecular determinant of gemcitabine efficacy. Excision repair cross-complementing group 1 gene (ERCC1), a component of the nucleotide excision repair complex, is important for platinum-induced DNA adduct repair. We hypothesized that selection of double-agent chemotherapy based on tumoral RRM1 and ERCC1 expression would be feasible and beneficial for patients with advanced NSCLC. Patients and Methods We conducted a prospective phase II clinical trial in patients with advanced NSCLC. Patients were required to have a dedicated tumor biopsy for determination of RRM1 and ERCC1 gene expression by real-time quantitative reverse transcriptase polymerase chain reaction. Double-agent chemotherapy consisting of carboplatin, gemcitabine, docetaxel, and vinorelbine was selected based on gene expression. Disease response and patient survival were monitored. Results Eighty-five patients were registered, 75 had the required biopsy without significant complications, 60 fulfilled all eligibility criteria, and gene expression analysis was not feasible in five patients. RRM1 expression ranged from 0 to 1,637, ERCC1 expression ranged from 1 to 8,103, and their expression was correlated (Spearman's rho = 0.46; P &lt; .01). Disease response was 44%. Overall survival was 59% and progression-free survival was 14% at 12 months, with a median of 13.3 and 6.6 months, respectively. Conclusion Therapeutic decision making based on RRM1 and ERCC1 gene expression for patients with advanced NSCLC is feasible and promising for improvement in patient outcome.
Degeneration of the Nonrecombining Regions in the Mating-Type Chromosomes of the Anther-Smut Fungi
Authors: Eric Fontanillas, Michael E. Hood, Hélène Badouin, Elsa Petit, Valérie Barbe, Jérôme Gouzy, Damien M. de Vienne, Gabriela Aguileta, Julie Poulain, Patrick Wincker, Zehua Chen, Su San Toh, Christina A. Cuomo, Michael H. Perlin, Pierre Gladieux, Tatiana Giraud
Journal: Molecular Biology and Evolution (2014)

Dimorphic mating-type chromosomes in fungi are excellent models for understanding the genomic consequences of recombination suppression. Their suppressed recombination and reduced effective population size are expected to limit the efficacy of natural selection, leading to genomic degeneration. Our aim was to identify the sequences of the mating-type chromosomes (a1 and a2) of the anther-smut fungi and to investigate degeneration in their nonrecombining regions. We used the haploid a1 Microbotryum lychnidis-dioicae reference genome sequence. The a1 and a2 mating-type chromosomes were both isolated electrophoretically and sequenced. Integration with restriction-digest optical maps identified regions of recombination and nonrecombination in the mating-type chromosomes. Genome sequence data were also obtained for 12 other Microbotryum species. We found strong evidence of degeneration across the genus in the nonrecombining regions of the mating-type chromosomes, with significantly higher rates of nonsynonymous substitution (dN/dS) than in nonmating-type chromosomes or in recombining regions of the mating-type chromosomes. The nonrecombining regions of the mating-type chromosomes also showed high transposable element content, weak gene expression, and gene losses. The levels of degeneration did not differ between the a1 and a2 mating-type chromosomes, consistent with the lack of homogametic/heterogametic asymmetry between them, and contrasting with X/Y or Z/W sex chromosomes.
Pulmonary hypertension in chronic obstructive pulmonary disease
Authors: J.A. Barberà, V.I. Peinado, S. Santos
Journal: European Respiratory Journal (2003)

Pulmonary hypertension is a common complication of chronic obstructive pulmonary disease (COPD). Its presence is associated with shorter survival and worse clinical evolution. In COPD, pulmonary hypertension tends to be of moderate severity and progresses slowly. However, transitory increases of pulmonary artery pressure may occur during exacerbations, exercise and sleep. Right ventricular function is only mildly impaired with preservation of the cardiac output. Structural and functional changes of pulmonary circulation are apparent at the initial stages of COPD. Recent investigations have shown endothelial dysfunction and changes in the expression of endothelium-derived mediators that regulate vascular tone and cell growth in the pulmonary arteries of patients with mild disease. Some of these changes are also present in smokers with normal lung function. Accordingly, it has been postulated that the initial event in the natural history of pulmonary hypertension in COPD could be the lesion of pulmonary endothelium by cigarette-smoke products. Long-term oxygen administration is the only treatment that slows down the progression of pulmonary hypertension in chronic obstructive pulmonary disease. Nevertheless, with this treatment pulmonary artery pressure rarely returns to normal values and the structural abnormalities of pulmonary vessels remain unaltered. Vasodilators are not recommended on the basis of their minimal clinical efficacy and because they impair pulmonary gas exchange. Recognition of the role of endothelial dysfunction in the physiopathology of pulmonary hypertension in chronic obstructive pulmonary disease opens new perspectives for the treatment of this complication.
Low field dedicated magnetic resonance imaging in untreated rheumatoid arthritis of recent onset
Authors: H Lindegaard
Journal: Annals of the Rheumatic Diseases (2001)

<h3>OBJECTIVE</h3> To compare a low field dedicated extremity magnetic resonance imaging system (E-MRI) with <i>x</i> ray and clinical examination, in the detection of inflammation and erosive lesions in wrist and metacarpophalangeal (MCP) joints in newly diagnosed, untreated rheumatoid arthritis (RA). <h3>PATIENTS AND METHODS</h3> Twenty five patients (disease duration ⩽1 year) and three healthy controls entered the study. An<i>x</i> ray examination and MRI (before and after intravenous injection of a contrast agent) of the 2nd–5th MCP joints and the wrist was performed. The number of erosions on<i>x</i> ray examination and MRI was calculated, and synovitis in the MCP joints and wrists was graded semiquantitatively. <h3>RESULTS</h3> E-MRI detected 57 bone erosions, whereas only six erosions were disclosed by<i>x</i> ray examination (ratio 9.5:1). Synovial hypertrophy grades were significantly higher in RA joints with clinical signs of joint inflammation—that is, swelling and/or tenderness (median 3, 5th–95th centile 1–4) than without these clinical signs (median 2, 5th–95th centile 1–3), p&lt;0.001. 51% of the joints without clinical signs of synovitis showed synovial hypertrophy on E-MRI. There was a positive correlation between MRI scores of synovitis and the number of erosions detected by MRI in the MCP joints (Spearman<i>r</i><sub>s</sub>=0.31, p&lt;0.01). No healthy controls had erosions or synovitis on MRI. <h3>CONCLUSION</h3> Joint destruction starts very early in RA and E-MRI allows detailed evaluation of inflammatory and destructive changes in wrists and MCP joints in patients with incipient RA.
Establishment of a human pro‐B cell line (JKB‐1) and its differentiation of preestablished bone marrow stromal cell layer
Authors: Mitsuyoshi Urashima, Notomi Hasegawa, Makoto Kamijo, Akihiro Shishikura, Yoko Kato, Yasutaka Hoshi, Jun‐Ichi Akatsuka, Kihei Maekawa
Journal: American Journal of Hematology (1994)

A human pro-B cell line, named JKB-1, was established from the bone marrow of a 16-year-old girl with acute lymphoblastic leukemia (ALL) in relapse. The origin of the JKB-1 cell line was indicated by its chromosomal and immunologic similarity to the patient's fresh leukemic cells. This cell line has been growing for more than 14 months in suspension culture medium and had a doubling time of about 24 hours. JKB-1 expressed terminal deoxynucleotide transferase (TdT) and early antigens (HLA-DR, CD19, CD24) of B cells, with heavy chain gene rearrangement. However, it did not express late antigens (CD10, CD20, CD21, CD22, CD23) of B cells, light chain gene rearrangement, and cytoplasmic mu-chain. These results suggested that JKB-1 is at the stage of "pro-B" cell or early B-cell precursors. This cell line was induced to differentiate after 7 days of co-incubation with irradiated bone marrow stromal cells because of the expression of pre-B cell antigens (CD10, CD20), cytoplasmic mu-chain, light chain gene rearrangement, and disappearance of TdT, JKB-1 cells adhered to a preestablished bone marrow stromal cell layer with string-like processes under scanning electron microscope. When JKB-1 cells were separated from the stromal layer by a cyclopore membrane with 0.45 micron pore size, they did not differentiate. Bone marrow stromal cell conditioned medium could not induce differentiation either. Thus it was suspected that direct contact between JKB-1 cells and stromal cells was required for differentiation. In methylcellulose semisolid medium, the colony size and number of JKB-1 cells were increased by stem cell factor (SCF), or interleukin (IL)-3, or IL-7, but they were decreased by IL-6. Moreover, SCF synergized with IL-3 or IL-7 to stimulate the proliferation of JKB-1 cells. Because there are very few reproducible models for examining early stages of human B-cell differentiation, the JKB-1 cell line would be useful for studying the relationship between human B-cell differentiation and bone marrow microenvironment, as well as leukemogenesis.
Antithrombins: Their Potential as Antithrombotic Agents
Authors: Jeffrey I. Weitz, Jack Hirsh
Journal: Annual Review of Medicine (1992)

The inhibition of thrombin is the key to the prevention and treatment of thrombotic disorders. Although heparin is an extremely effective anticoagulant, it has certain limitations that are not shared by newer thrombin inhibitors. As a result, these novel inhibitors may have advantages over heparin in certain clinical settings.
NAD(P)H:Quinone Oxidoreductase 1 and NRH:Quinone Oxidoreductase 2 Activity and Expression in Bladder and Ovarian Cancer and Lower NRH:Quinone Oxidoreductase 2 Activity Associated with an NQO2 Exon 3 Single-Nucleotide Polymorphism
Authors: David Jamieson, Kerrie Wilson, Simon Pridgeon, Jane P. Margetts, Richard J. Edmondson, Hing Y. Leung, Richard Knox, Alan V. Boddy
Journal: Clinical Cancer Research (2007)

Abstract Purpose: NRH:quinone oxidoreductase 2 (NQO2) is a homologue of NAD(P)H:quinone oxidoreductase 1 (NQO1). Despite 54% homology with human NQO1, NQO2 has little endogenous enzymatic activity. However, NQO2 has potential as a therapeutic target because the addition of the nonbiogenic electron donor dihydronicotinamide riboside (NRH) selectively potentiates the bioactivation of the alkylating agent tretazicar (CB 1954). The NQO activity of ovarian and bladder tumors was determined and the effect of NQO polymorphisms on NQO activity was investigated. Experimental Design: Intraperitoneal ovarian metastases and bladder tumor clinical samples were analyzed for NQO1 and NQO2 activity, mRNA expression by semiquantitative reverse transcription-PCR, and genotype by RFLP analysis. Results: NQO1 activity was higher in the bladder cohort than in the ovarian cohort (0-283 and 0-30 nmol/min/mg, respectively; P &amp;lt; 0.0001). In contrast, NQO2 activity was higher in the ovarian tissue than in the bladder samples (0.15-2.27 and 0-1.14 nmol/min/mg, respectively; P = 0.0004). In both cohorts, the NQO1 C609T single-nucleotide polymorphism (SNP) was associated with ∼7-fold lower NQO1 activity. The NQO2 exon 3 T14055C SNP was associated with lower NQO2 activity relative to wild-type [median values of 0.18 and 0.37 nmol/min/mg in the bladder samples (P = 0.007) and 0.82 and 1.16 nmol/min/mg in the ovarian cohort (P = 0.034)]. Conclusion: This is the first observation reporting an apparent association between an NQO2 exon 3 SNP and lower enzymatic activity. The high NQO2 activity of intraperitoneal ovarian metastases relative to other tissues indicates a potential for tretazicar therapy in the treatment of this disease. In contrast, the low level of NQO1 activity and expression relative to other tissues suggests that NQO1-directed therapies would not be appropriate.