tbuckley/cabot-search huggingface dataset:
Cardioprotection by ε-Protein Kinase C Activation From Ischemia
Authors: Koichi Inagaki, Rebecca Begley, Fumiaki Ikeno, Daria Mochly-Rosen
Journal: Circulation (2004)

We previously showed that a selective activator peptide of epsilon-protein kinase C (PKC), psi(epsilon)RACK, conferred cardioprotection against ischemia-reperfusion when delivered ex vivo before the ischemic event. Here, we tested whether in vivo continuous systemic delivery of psi(epsilon)RACK confers sustained cardioprotection against ischemia-reperfusion in isolated mouse hearts and whether psi(epsilon)RACK treatment reduces infarct size or lethal arrhythmias in porcine hearts in vivo.After psi(epsilon)RACK was systemically administered in mice either acutely or continuously, hearts were subjected to ischemia-reperfusion in an isolated perfused model. Whereas psi(epsilon)RACK-induced cardioprotection lasted 1 hour after a single intraperitoneal injection, continuous treatment with psi(epsilon)RACK induced a sustained preconditioned state during the 10 days of delivery. There was no desensitization to the therapeutic effect, no downregulation of epsilonPKC, and no adverse effects after sustained psi(epsilon)RACK delivery. Porcine hearts were subjected to ischemia-reperfusion in vivo, and psi(epsilon)RACK was administered by intracoronary injection during the first 10 minutes of ischemia. psi(epsilon)RACK treatment reduced infarct size (34+/-2% versus 14+/-1%, control versus psi(epsilon)RACK) and resulted in fewer cases of ventricular fibrillation during ischemia-reperfusion (87.5% versus 50%, control versus psi(epsilon)RACK).The epsilonPKC activator psi(epsilon)RACK induced cardioprotection both in vivo and ex vivo, reduced the incidence of lethal arrhythmia during ischemia-reperfusion, and did not cause desensitization or downregulation of epsilonPKC after sustained delivery. Thus, psi(epsilon)RACK may be useful for patients with ischemic heart disease. In addition, the psi(epsilon)RACK peptide should be a useful pharmacological agent for animal studies in which systemic and sustained modulation of epsilonPKC in vivo is needed.
Diagnosing Pulmonary Embolism With Improved Certainty and Simplicity
Authors: Russell D. Hull
Journal: JAMA (2006)

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
Immunological regulation of experimental cutaneous leishmaniasis. III. Nature and significance of specific suppression of cell-mediated immunity in mice highly susceptible to Leishmania tropica.
Authors: J G Howard, C Hale, F Y Liew
Journal: The Journal of Experimental Medicine (1980)

BALB/c mice have been an exceptional susceptibility to Leishmania tropica infection such that cutaneous lesions grow without restraint in all cases leading to fatal metastasis and visceralization in normal and x-irradiated, bone-marrow reconstituted (XBM) animals. Adult thymectomized, x-irradiated, bone marrow-reconstituted (ATxXBM) BALB/c mice, however, show pronounced retardation of lesion growth leading to some survival and even cures. A similar trend was also found in moderately susceptible (BALB/c X C57BL/6)F1 mice, in contrast with the "resistant" CBA strain, in which, as previously known, ATxXBM animals showed impairment of normal, spontaneous self-healing. These convere effects are paralleled by respective leishmania-specific delayed-type hypersensitivity (DTH) reactivities, prior thymectomy leading to diminution in CBA and augmentation in BALB/c and (BALB/c X C57BL/6)F1. Anti-leishmanial DTH responses, amplfiable by cyclophosphamide pretreatment, can be detected in BALB/c mice within 10 d of infection with 2 X 10(7) promastigotes, but becomes near-totally suppressed by day 25-35. No such suppressin is found in CBA, C57BL/6, or (BALB/c X C57BL/6)F1 mice together with varying degrees of immune control of lesion development or regression. Suppression of DTH in BALB/c mice is leishmania specific and does not extent to 2,4-dinitrofluorobenzene (DNFB) or sheep erythrocytes specificities. Spleen cells from suppressed L. tropica-infected mice when transferred to normal BALB/c mice impaired the induction of DTH to leishmanial antigen. This property resided in the T cell-enriched fraction and not in the T cell-depleted fraction. It is concluded that a major component of the striking inability of BALB/c mice to control L. tropica infection involves profound impairment of a potentially curative cell-mediated immune response by suppressor T cell generation. The possibility is discussed that this may be secondary to rapid amastigote (antigen) accumulation in macrophages expressing the primary genetic "defect."
Predictors of Primary Imatinib Resistance in Chronic Myelogenous Leukemia Are Distinct From Those in Secondary Imatinib Resistance
Authors: Wenyong W. Zhang, Jorge E. Cortes, Hui Yao, Li Zhang, Neelima G. Reddy, Elias Jabbour, Hagop M. Kantarjian, Dan Jones
Journal: Journal of Clinical Oncology (2009)

A subset of patients with chronic myelogenous leukemia (CML) do not respond to the tyrosine kinase inhibitor (TKI) imatinib mesylate. Such primary imatinib resistance is distinguished from secondary resistance which reemerges after attainment of cytogenetic remission.We studied gene expression patterns in total WBCs using a panel of 21 genes previously implicated in TKI handling, resistance, or progression comparing patients who had newly diagnosed TKI-naive CML that had optimal (n = 41), or suboptimal (n = 7) responses to imatinib, or primary resistance (n = 20). Expression patterns were compared to those in secondary TKI-resistant chronic phase CML without ABL1 kinase domain mutations (n = 29), and to lymphoid (n = 15) or myeloid blast phase disease (n = 12).Fifteen genes in the panel distinguished blast phase from chronic phase disease, and 12 genes distinguished newly diagnosed CML from TKI-resistant CML without ABL1 kinase domain mutations, but only a single gene, prostaglandin-endoperoxide synthase 1/cyclooxgenase 1 (PTGS1/COX1; P = .005), differentiated imatinib-responsive from primary imatinib-resistant CML. The association of primary imatinib resistance with higher transcript levels of the drug metabolism gene PTGS1 was confirmed in a separate data set of 68 newly diagnosed, imatinib-treated CML (P = .008). In contrast, up to 11 different genes were identified in a multivariate model that optimally discriminated secondary imatinib resistance lacking ABL1 kinase domain mutation from imatinib-responsive cases, likely related to the more complex pathogenesis of secondary resistance.Gene expression profiling of CML at diagnosis for PTGS1 may be useful in predicting imatinib response and in selecting alternate therapy.
Carcinogenic Effect of N -Nitroso-2,6-dimethylmorpholine in Syrian Golden Hamsters
Authors: Gerd Reznik, Ulrich Mohr, William Lijinsky
Journal: JNCI Journal of the National Cancer Institute (1978)

N-Nitroso-2,6-dimethylmorpholine was intragastrically administered to Syrian golden hamsters at four different dose levels [74 mg/kg body wt = 1/5 median lethal dose (LD50); 37 mg/kg body wt = 1/10 LD50; 18 mg/kg body wt = 1/20 LD50; and 9 mg/kg body wt = 1/40 LD50]. Up to a 71% rate of pancreatic tumors was induced. These tumors were adenomas or adenocarcinomas of ductal origin. In addition, neoplasms developed in different percentages in the nasal cavities, larynx, trachea, lungs, liver, gallbladder, kidneys, and forestomach. The number of tumors induced was not significantly dose-dependent.
National body to prevent research fraud is proposed
Authors: Bryan Christie
Journal: BMJ (2001)

Proposals have been put forward to establish a national organisation in the United Kingdom that would identify and investigate suspected cases of fraud and misconduct in clinical and biological research.

It would aim to promote high standards in research to help prevent misconduct and would have powers to investigate in cases giving rise to suspicion.

The plans, for a government funded national panel for research integrity, have been put forward by the Royal College of Physicians of Edinburgh, the …
Strategic Workshops on Cancer Nanotechnology
Authors: Larry A. Nagahara, Jerry S.H. Lee, Linda K. Molnar, Nicholas J. Panaro, Dorothy Farrell, Krzysztof Ptak, Joseph Alper, Piotr Grodzinski
Journal: Cancer Research (2010)

Nanotechnology offers the potential for new approaches to detecting, treating, and preventing cancer. To determine the current status of the cancer nanotechnology field and the optimal path forward, the National Cancer Institute's Alliance for Nanotechnology in Cancer held three strategic workshops, covering the areas of in vitro diagnostics and prevention, therapy and post-treatment, and in vivo diagnosis and imaging. At each of these meetings, a wide range of experts from academia, industry, the nonprofit sector, and the U.S. government discussed opportunities in the field of cancer nanotechnology and barriers to its implementation.
Specific mutations in enhancer II/core promoter of hepatitis B virus subgenotypes C1/C2 increase the risk of hepatocellular carcinoma
Authors: Yasuhito Tanaka, Motokazu Mukaide, Etsuro Orito, Man-Fung Yuen, Kiyoaki Ito, Fuat Kurbanov, Fuminaka Sugauchi, Yasuhiro Asahina, Namiki Izumi, Michio Kato, Ching-Lung Lai, Ryuzo Ueda, Masashi Mizokami
Journal: Journal of Hepatology (2006)
Superoxide Production and Expression of Nox Family Proteins in Human Atherosclerosis
Authors: Dan Sorescu, Daiana Weiss, Bernard Lassègue, Roza E. Clempus, Katalin Szöcs, George P. Sorescu, Liisa Valppu, Mark T. Quinn, J. David Lambeth, J. David Vega, W. Robert Taylor, Kathy K. Griendling
Journal: Circulation (2002)

NAD(P)H oxidases are important sources of superoxide in the vasculature, the activity of which is associated with risk factors for human atherosclerosis. This study was designed to investigate the localization of superoxide production and the expression of the Nox family of NAD(P)H oxidase proteins (gp91phox, Nox1, and Nox4) in nonatherosclerotic and atherosclerotic human coronary arteries.In coronary artery segments from explanted human hearts, we examined intracellular superoxide production with dihydroethidium. In nonatherosclerotic coronary arteries, superoxide was present homogenously throughout the intima, media, and adventitia. In atherosclerotic arteries, there was an additional intense area of superoxide in the plaque shoulder, which is rich in macrophages and alpha-actin-positive cells. p22phox colocalized with gp91phox mainly in macrophages, whereas Nox4 was found only in nonphagocytic vascular cells. Expression of gp91phox and p22phox mRNA was associated with the severity of atherosclerosis. gp91phox correlated with the plaque macrophage content, whereas Nox4 correlated with the content of alpha-actin-positive cells. Nox1 expression was low both in human coronary arteries and isolated vascular cells.Several Nox proteins, including gp91phox and Nox4, may contribute to increased intracellular oxidative stress in human coronary atherosclerosis in a cell-specific manner and thus may be involved in the genesis and progression of human coronary atherosclerotic disease.
Secondary Sarcomas in Childhood Cancer Survivors: A Report From the Childhood Cancer Survivor Study
Authors: T. O. Henderson, J. Whitton, M. Stovall, A. C. Mertens, P. Mitby, D. Friedman, L. C. Strong, S. Hammond, J. P. Neglia, A. T. Meadows, L. Robison, L. Diller
Journal: JNCI Journal of the National Cancer Institute (2007)

Childhood cancer survivors are at increased risk for the development of secondary sarcomas. Exposure to radiation therapy is a known risk factor for the development of these sarcomas. Other risk factors for secondary sarcomas have not been well described for childhood cancer survivors. We analyzed a large cohort of childhood cancer survivors to determine the true incidence of secondary sarcomas and to examine factors associated with the risk of developing secondary sarcomas. The history of secondary sarcomas in 14 372 participants in the Childhood Cancer Survivor Study was determined from self-reports in three questionnaires. Risk of secondary sarcoma was evaluated by use of standardized incidence ratios (SIRs) and excess absolute risks (EARs) as calculated by use of data from the Surveillance, Epidemiology, and End Results Program. Cox regression models were used to estimate hazard ratios of developing subsequent sarcomas. Hazard ratios were reported as relative risks (RRs). We identified 108 patients with sarcomas that were diagnosed a median of 11 years after the diagnosis of childhood cancer. The risk of sarcoma was more than ninefold higher among childhood cancer survivors than among the general population (SIR = 9.02, 95% confidence interval [CI] = 7.44 to 10.93). The excess absolute risk of secondary sarcoma was 32.5 per 100 000 person-years (95% CI = 26.1 to 40.3 per 100 000 person-years). Higher standardized incidence ratios and excess absolute risks were associated with young age at primary diagnosis, primary sarcoma diagnosis, and a family history of cancer. In a multivariable model, increased risk of secondary sarcoma was associated with radiation therapy (RR = 3.1, 95% CI = 1.5 to 6.2), with a primary diagnosis of sarcoma (RR = 10.1, 95% CI = 4.7 to 21.8), with a history of other secondary neoplasms (RR = 2.2, 95% CI = 1.1 to 4.5), and with treatment with higher doses of anthracyclines (RR = 2.3, 95% CI = 1.2 to 4.3) or alkylating agents (RR = 2.2, 95% CI = 1.1 to 4.6). Childhood cancer survivors appear to be at increased risk for secondary sarcomas compared with general population rates.
Acute Complications and Drug Misuse Are Important Causes of Death for Children and Young Adults With Type 1 Diabetes
Authors: Richard G. Feltbower, H. Jonathan Bodansky, Christopher C. Patterson, Roger C. Parslow, Carolyn R. Stephenson, Catherine Reynolds, Patricia A. McKinney
Journal: Diabetes Care (2008)

To examine mortality rates and causes of death among subjects diagnosed with type 1 diabetes aged <or=29 years.Subjects with type 1 diabetes from a population-based register in Yorkshire, U.K., diagnosed between 1978 and 2004 were linked to the U.K. National Health Service Central Register for death notifications. Deaths were coded using ICD-9 (1979-2000) and ICD-10 (2001-2005). Standardized mortality ratios (SMRs) were calculated using expected numbers of deaths from U.K. mortality rates by cause of death and age at diagnosis.A total of 4,246 individuals were followed up, providing 50,471 person-years of follow-up. Mean follow-up length was 12.8 years for individuals aged 0-14 years and 8.3 for those aged 15-29 years. Overall, 108 patients died, of whom 77 (71%) were male. A total of 74 (1.7/1,000 person-years) deaths occurred in inidividuals aged 0-14 years and 34 (4.6/1,000 person-years) in those aged 15-29 years. The SMR was 4.7 (95% CI 3.8-5.6) overall, similar for males and females, but higher for individuals aged 15-29 years (SMR 6.2 [95% CI 4.3-8.6]) compared with those aged 0-14 years (4.2 [3.3-5.3]). The SMR rose with increasing disease duration. A total of 47 of 108 deaths (44%) occurred from diabetes complications, 32 of which were acute and 15 chronic. Twenty-two percent (n = 24) of deaths were attributed to accidents or violence (SMR 2.1 [95% CI 1.4-3.2]), including six suicides. Sixteen percent of all deaths were related to drug misuse (including insulin but excluding tobacco and alcohol) (SMR 6.4 [95% CI 3.7-10.2]).Subjects with type 1 diabetes diagnosed under 30 years of age had a 4.7-fold excess mortality risk. Nearly half of the deaths were due to acute or chronic complications of diabetes. Drug misuse-related deaths may be an emerging trend in this population warranting further investigation.
A Theoretically Based Index of Consciousness Independent of Sensory Processing and Behavior
Authors: Adenauer G. Casali, Olivia Gosseries, Mario Rosanova, Mélanie Boly, Simone Sarasso, Karina R. Casali, Silvia Casarotto, Marie-Aurélie Bruno, Steven Laureys, Giulio Tononi, Marcello Massimini
Journal: Science Translational Medicine (2013)

A theory-derived index of consciousness, which quantifies the complexity of the brain’s response to a stimulus, measures the level of consciousness in awake, sleeping, anesthetized, and brain-damaged subjects.
Early abnormalities of pisiform and triquetrum in rheumatoid arthritis.
Authors: D Resnick
Journal: Annals of the Rheumatic Diseases (1976)

Erosions on the triquetrum and pisiform are frequent in early rheumatoid arthritis and occur characteristically at 3 sites. (a) A shallow erosion on the proximal medial triquetral "bare" area is related to synovial proliferation at the margin of the radiocarpal cavity, although compressive forces from an adjacent long ulnar styloid may be contributory; (b) an erosive abnormality on the distal medial triquetrum is related to synovial proliferation along the margin of the midcarpal joint; and (c) ring-like erosions on apposing surfaces of the triquetrum and pisiform are produced by pannus within the pisiform-triquetral compartment.
Urinary Megalin Deficiency Implicates Abnormal Tubular Endocytic Function in Fanconi Syndrome
Authors: Anthony G. W. Norden, Marta Lapsley, Takashi Igarashi, Catherine L. Kelleher, Philip J. Lee, Takeshi Matsuyama, Steven J. Scheinman, Hiroshi Shiraga, David P. Sundin, Rajesh V. Thakker, Robert J. Unwin, Pierre Verroust, Søren K. Moestrup
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Normal reabsorption of glomerular filtrate proteins probably requires recycling of the endocytic receptors megalin (gp330) and cubilin. Both receptors are located on the luminal surface of the renal proximal tubule epithelium. Whether abnormal amounts of receptor are present in the urine of patients with Dent's disease, Lowe's syndrome, or autosomal dominant idiopathic Fanconi syndrome was explored. They are all forms of the renal Fanconi syndrome and are associated with tubular proteinuria. Urine samples of equal creatinine contents were dialyzed, lyophilized, and subjected to electrophoresis on nonreducing sodium dodecyl sulfate-5% polyacrylamide gels. Proteins were blotted and probed with anti-megalin IgG, anti-cubilin IgG, or receptor-associated protein. Megalin and cubilin levels detected by immunochemiluminescence were measured as integrated pixels and expressed as percentages of the normal mean values. A striking deficiency of urinary megalin, compared with normal individuals (n = 42), was observed for eight of nine families with Dent's disease (n = 10) and for the two families with Lowe's syndrome (n = 3). The family with autosomal dominant idiopathic Fanconi syndrome (n = 2) exhibited megalin levels within the normal range. The measured levels of cubilin were normal for all patients. These results are consistent with defective recycling of megalin to the apical cell surface of the proximal tubules and thus decreased loss into urine in Dent's disease and Lowe's syndrome. This defect would interfere with the normal endocytic function of megalin, result in losses of potential ligands into the urine, and produce tubular proteinuria.
Estimating Selection on Synonymous Codon Usage from Noisy Experimental Data
Authors: Edward W.J. Wallace, Edoardo M. Airoldi, D. Allan Drummond
Journal: Molecular Biology and Evolution (2013)

A key goal in molecular evolution is to extract mechanistic insights from signatures of selection. A case study is codon usage, where despite many recent advances and hypotheses, two longstanding problems remain: the relative contribution of selection and mutation in determining codon frequencies and the relative contribution of translational speed and accuracy to selection. The relevant targets of selection—the rate of translation and of mistranslation of a codon per unit time in the cell—can only be related to mechanistic properties of the translational apparatus if the number of transcripts per cell is known, requiring use of gene expression measurements. Perhaps surprisingly, different gene-expression data sets yield markedly different estimates of selection. We show that this is largely due to measurement noise, notably due to differences between studies rather than instrument error or biological variability. We develop an analytical framework that explicitly models noise in expression in the context of the population-genetic model. Estimates of mutation and selection strength in budding yeast produced by this method are robust to the expression data set used and are substantially higher than estimates using a noise-blind approach. We introduce per-gene selection estimates that correlate well with previous scoring systems, such as the codon adaptation index, while now carrying an evolutionary interpretation. On average, selection for codon usage in budding yeast is weak, yet our estimates show that genes range from virtually unselected to average per-codon selection coefficients above the inverse population size. Our analytical framework may be generally useful for distinguishing biological signals from measurement noise in other applications that depend upon measurements of gene expression.
Flexible Intensive Versus Conventional Insulin Therapy in Insulin-Naive Adults With Type 2 Diabetes
Authors: Christof Kloos, Alexander Sämann, Thomas Lehmann, Anke Braun, Barbara Heckmann, Ulrich A. Müller
Journal: Diabetes Care (2007)

Improving metabolic control can reduce complications in type 2 diabetes (1–4). Conventional insulin therapy (CIT) and flexible intensive insulin therapy (FIT) are treatment options in insulin-dependent type 2 diabetic patients. In CIT, participants inject premixed human insulin (30% regular insulin, 70% NPH insulin) before breakfast and dinner and follow individually adjusted diet plans with fixed amounts of carbohydrates (5). In FIT, human regular insulin is adjusted before main meals according to current blood glucose readings and desired carbohydrate intake. When necessary, NPH insulin is added at bedtime. CIT can be easy to handle and requires less active diabetes self-management. In FIT, patients benefit from dietary freedom and improvement in quality of life (6). In pilot studies, FIT has shown good metabolic control and low risk of hypoglycemia (7). FIT may have additional advantages due to better postprandial blood glucose control (8).

We tested the hypothesis that FIT and CIT in insulin-naive adults with type 2 diabetes are equally effective in regard to metabolic outcomes. We hypothesized that younger participants, in employment, would prefer FIT.

The trial was designed as a clinical, prospective, randomized, open-label, single-center, crossover study. The primary end point was glycosylated hemoglobin A1c (GHb); secondary end points were mild and severe hypoglycemia, insulin dosage, blood pressure, BMI, and therapy preference. Participants started insulin therapy either with CIT (group A) or FIT (group B), randomly. Individual insulin dosage and carbohydrate intake were determined …