tbuckley/cabot-search huggingface dataset:
Role of phorbol diesters in in vitro murine megakaryocyte colony formation.
Authors: M W Long, J E Smolen, P Szczepanski, L A Boxer
Journal: Journal of Clinical Investigation (1984)

In vitro megakaryocyte differentiation is regulated by two activities: a megakaryocyte colony-stimulating activity (Mk-CSA), which is required for proliferation, and an auxiliary factor, megakaryocyte potentiating activity, which plays a role in later differentiation events. Tumor-promoting phorbol esters alter many cellular differentiation-related events. Thus, it was hypothesized that phorbol esters may bring about megakaryocyte differentiation in vitro. 4 beta-Phorbol 12-myristate 13-acetate (PMA), when co-cultured with a source of Mk-CSA, stimulated a threefold increase in colony numbers. Co-culture of PMA and megakaryocyte potentiator activity did not stimulate colony formation, thus eliminating any action of PMA as an Mk-CSA. The direct effect of PMA on the formation of megakaryocyte colonies was established by (a) the function of PMA as a megakaryocyte potentiator in serum-free experiments, (b) the ability of PMA to stimulate megakaryocyte colony formation using bone marrow cells depleted of populations known to produce potentiating activity, (c) the inability of bone marrow adherent cells previously treated with phorbol, 12,13-dibutyrate (PDBu) to augment megakaryocyte colony formation, and (d) the ability of PMA to induce the growth of immature megakaryocytes into large single megakaryocytes. Structure:activity experiments resulted in equivalent activities for PMA and PDBu, whereas the nontumor promoter phorbol 12,13-diacetate and phorbol itself lacked activity. The observations in this study indicate that phorbol esters can bring about megakaryocyte differentiation, and during colony formation, can induce effects identical to those brought about by biological sources of megakaryocyte potentiator activity.
Electron tomography of respiratory cilia
Authors: Amelia Shoemark, Claire Hogg
Journal: Thorax (2012)

Cilia are organelles present on almost every cell within the body. In the respiratory tract, motile cilia line the epithelial surface and beat in a coordinated fashion to clear mucus from the airways. Mucociliary dysfunction is implicated in a number of lung diseases including cystic fibrosis, chronic obstructive pulmonary disease, bronchiectasis and primary ciliary dyskinesia. Recent microscopy advances such as electron tomography have developed our understanding of the structure and function of these important organelles. In this review we discuss electron tomography and its relevance to respiratory cilia.
p21 promotes sustained liver regeneration and hepatocarcinogenesis in chronic cholestatic liver injury
Authors: Silke Marhenke, Laura Elisa Buitrago-Molina, Jessica Endig, Johanna Orlik, Nora Schweitzer, Stephanie Klett, Thomas Longerich, Robert Geffers, Aránzazu Sánchez Muñoz, Craig Dorrell, Sarah-Fee Katz, André Lechel, Honglei Weng, Till Krech, Ulrich Lehmann, Steven Dooley, Karl Lenhard Rudolph, Michael P Manns, Arndt Vogel
Journal: Gut (2013)

<h3>Background and aims</h3> The cyclin-dependent kinase inhibitor p21 has been implicated as a tumour suppressor. Moreover, recent genetic studies suggest that p21 might be a potential therapeutic target to improve regeneration in chronic diseases. The aim of this study was to delineate the role of p21 in chronic liver injury and to specify its role in hepatocarcinogenesis in a mouse model of chronic cholestatic liver injury. <h3>Methods</h3> The degree of liver injury, regeneration and tumour formation was assessed in <i>Mdr2<sup>−/−</sup></i> mice and compared with <i>Mdr2/ p21<sup>−/−</sup></i> mice. Moreover, the role of p21 was evaluated in hepatoma cells <i>in vitro</i> and in human hepatocellular carcinoma (HCC). <h3>Results</h3> <i>Mdr2<sup>−/−</sup></i> mice developed HCCs as a consequence of chronic inflammatory liver injury. In contrast, tumour development was profoundly delayed in <i>Mdr2/ p21<sup>−/−</sup></i> mice. Delayed tumour development was accompanied by markedly impaired liver regeneration in <i>Mdr2/ p21<sup>−/−</sup></i> mice. Moreover, the regenerative capacity of the <i>Mdr2/ p21<sup>−/−</sup></i> livers in response to partial hepatectomy declined with age in these mice. Hepatocyte transplantation experiments revealed that impaired liver regeneration was due to intrinsic factors within the cells and changes in the <i>Mdr2/ p21<sup>−/−</sup></i> microenvironment. In human HCCs, a subset of tumours expressed p21, which was associated with a significant shorter patient survival. <h3>Conclusions</h3> We provide experimental evidence that p21 is required for sustained liver regeneration and tumour development in chronic liver injury indicating that p21 needs to be tightly regulated in order to balance liver regeneration and cancer risk. Moreover, we identify p21 as a negative prognostic marker in human HCC.
Prevalence of hepatitis C virus infection in patients with rheumatoid arthritis
Authors: J F Maillefert
Journal: Annals of the Rheumatic Diseases (2002)

Various viruses have been implicated in the cause and pathogenesis of rheumatoid arthritis (RA). Hepatitis C virus (HCV) infection, which has been recognised as a cause of some autoimmune diseases, and which has been described as sometimes presenting with rheumatic manifestations indistinguishable from RA, might be a candidate.To evaluate the prevalence of HCV infection in patients with RA.Consecutive patients with RA admitted to hospital in two departments of rheumatology were prospectively studied. Patients' serum samples were screened for the presence of anti-HCV antibodies. Patients with positive serology were further evaluated for the presence of HCV ribonucleic acid by reverse transcriptase polymerase chain reaction (RT-PCR).309 patients (232 women, 77 men, mean age (SD) 54.1 (14.8) years) were studied. Their mean (SD) disease duration was 74.1 (91) months. Tests for rheumatoid factors and antinuclear antibodies were positive in 213 (69%) and 114 (37%) of the patients respectively. Systemic vasculitis was found in 12 (4%) of the patients. Mean erythrocyte sedimentation rate was 36.4 (SD 30.5) mm at the first hour (normal <10 mm) and C reactive protein was 36.8 (SD 45.8) mg/l (normal range <5 mg/l), respectively, with 181(58.6%) of patients considered as having active disease. Aspartate transaminases were increased in 14 (4%) patients, and alkaline phosphatase in 14 (4%). A positive anti-HCV serology was found in two (0.65%) patients, including one with a previously diagnosed HCV infection. HCV RNA was positive by RT-PCR in one of those two patients.A 0.65% prevalence of past or active HCV infection was found in patients with RA, which did not differ from the prevalence of HCV in the general French population. This result does not support the participation of HCV infection in the pathogenesis of RA.
Influenza and Its Global Public Health Significance
Authors: W. Paul Glezen
Journal: JAMA (2007)

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
Molecular Profiling of Human Hepatocellular Carcinoma Defines Mutually Exclusive Interferon Regulation and Insulin-Like Growth Factor II Overexpression
Authors: Kai Breuhahn, Sebastian Vreden, Ramsi Haddad, Susanne Beckebaum, Dirk Stippel, Peer Flemming, Tanja Nussbaum, Wolfgang H. Caselmann, Brian B. Haab, Peter Schirmacher
Journal: Cancer Research (2004)

Abstract Molecular subtyping of human hepatocellular carcinoma (HCC) with potential mechanistic and therapeutic impact has not been achieved thus far. We have analyzed the mRNA expression patterns of 43 different human HCC samples and 3 HCC cell lines in comparison with normal adult liver using high-density cDNA microarrays. Two main groups of HCC, designated group A (65%) and group B (35%), were distinguished based on clustering of the most highly varying genes. Group A HCCs were characterized by induction of a number of interferon (IFN)-regulated genes, whereas group B was characterized mainly by down-regulation of several apoptosis-relevant and IFN-regulated genes. The number of apoptotic tumor cells and tumor-infiltrating lymphocytes was significantly higher in tumors of group A as compared with those of group B. Based on the expression pattern, group B was further subdivided into two subgroups, designated subgroup B1 (6 of 43 tumors, 14%) and subgroup B2 (9 of 43 tumors, 21%). A prominent characteristic of subgroup B1 was high overexpression of insulin-like growth factor (IGF)-II. All tested HCC cell lines expressed equally high concentrations of IGF-II transcripts and co-segregated with group B1 in clustering. IGF-II overexpression and induction of IFN-related genes were mutually exclusive, even when analysis was extended to other cancer expression profile studies. Moreover, IFN-γ treatment substantially reduced IGF-II expression in HCC cells. In conclusion, cDNA microarray analyses provided subtyping of HCCs that is related to intratumor inflammation and tumor cell apoptosis. This profiling may be of mechanistic and therapeutic impact because IGF-II overexpression has been linked to reduced apoptosis and increased proliferation and may be accessible to therapeutic intervention.
Treatment of psoriasis and atopic dermatitis with halcinonide cream applied once and three times daily
Authors: TORSTEN FREDRIKSSON, ALLAN LASSUS, JOHAN BLEEKER
Journal: British Journal of Dermatology (1980)

SUMMARY In a double-blind multi-centre study, comprising ninety-five patients with psoriasis and atopic dermatitis, 0.1% halcinonide cream applied once daily was equally as effective as the cream applied three times daily. However, the onset of action was more rapid when the cream was applied three times daily. In a control study once daily application of 0.1% halcinonide cream was found to be superior to the vehicle alone in the treatment of forty patients with the same diseases.
Post-recurrence survival in completely resected stage I non-small cell lung cancer with local recurrence
Authors: J-J Hung, W-H Hsu, C-C Hsieh, B-S Huang, M-H Huang, J-S Liu, Y-C Wu
Journal: Thorax (2009)

Resection is the best treatment for patients with stage I non-small cell lung cancer (NSCLC). Patterns of disease recurrence after complete resection in stage I NSCLC have not been well demonstrated. The aim of this study was to evaluate the prognostic predictors of post-recurrence survival in patients with resected stage I NSCLC with local recurrence.The clinicopathological characteristics of 123 patients with local recurrence after complete resection of stage I NSCLC in Taipei Veterans General Hospital between 1980 and 2000 were retrospectively reviewed. Post-recurrence survival and their predictors were analysed.The patterns of local recurrence included local only in 74 (60.2%) and both local and distant in 49 (39.8%) patients. The 1 and 2 year post-recurrence survival rates for the 74 patients with local only recurrence were 48.7% and 17.6%, respectively. Tumour size (p = 0.033) and treatment for initial recurrence (p<0.001) were significant predictors for post-recurrence survival in 74 patients with local only recurrence in univariate analyses. The hazard of death was greater in patients with larger tumour size. Treatment for initial recurrence (p = 0.001) was still a significant prognostic indicator in multivariate analyses. Patients who underwent reoperation after local recurrence survived longer than those who received chemotherapy and/or radiotherapy and those that received no treatment.Treatment for initial recurrence is a prognostic predictor for post-recurrence survival in resected stage I NSCLC with local recurrence. Complete surgical resection should be considered in selected candidates with resectable local recurrent disease.
Promotion of CHIP-Mediated p53 Degradation Protects the Heart From Ischemic Injury
Authors: Atsuhiko T. Naito, Sho Okada, Tohru Minamino, Koji Iwanaga, Mei-Lan Liu, Tomokazu Sumida, Seitaro Nomura, Naruhiko Sahara, Tatsuya Mizoroki, Akihiko Takashima, Hiroshi Akazawa, Toshio Nagai, Ichiro Shiojima, Issei Komuro
Journal: Circulation Research (2010)

Rationale : The number of patients with coronary heart disease, including myocardial infarction, is increasing and novel therapeutic strategy is awaited. Tumor suppressor protein p53 accumulates in the myocardium after myocardial infarction, causes apoptosis of cardiomyocytes, and plays an important role in the progression into heart failure. Objectives : We investigated the molecular mechanisms of p53 accumulation in the heart after myocardial infarction and tested whether anti-p53 approach would be effective against myocardial infarction. Methods and Results : Through expression screening, we found that CHIP (carboxyl terminus of Hsp70-interacting protein) is an endogenous p53 antagonist in the heart. CHIP suppressed p53 level by ubiquitinating and inducing proteasomal degradation. CHIP transcription was downregulated after hypoxic stress and restoration of CHIP protein level prevented p53 accumulation after hypoxic stress. CHIP overexpression in vivo prevented p53 accumulation and cardiomyocyte apoptosis after myocardial infarction. Promotion of CHIP function by heat shock protein (Hsp)90 inhibitor, 17-allylamino-17-demethoxy geldanamycin (17-AAG), also prevented p53 accumulation and cardiomyocyte apoptosis both in vitro and in vivo. CHIP-mediated p53 degradation was at least one of the cardioprotective effects of 17-AAG. Conclusions : We found that downregulation of CHIP level by hypoxia was responsible for p53 accumulation in the heart after myocardial infarction. Decreasing the amount of p53 prevented myocardial apoptosis and ameliorated ventricular remodeling after myocardial infarction. We conclude that anti-p53 approach would be effective to treat myocardial infarction.
Developmental changes in the sensitivity of the chick embryo ventricle to beta-adrenergic agonist during adrenergic innervation.
Authors: D Higgins, A J Pappano
Journal: Circulation Research (1981)

As early as the 4th embryonic day, the ventricle of the chick embryo responded to isoproterenol (Iso) with an increase in the force of contraction; at all ages studied, this positive inotropic effect was accompanied by an increased rate of tension development. There was a transient, 10-fold decrease in the sensitivity (increase in ED50) of the right ventricle to Iso between the 16th and 21st embryonic day. This change in the sensitivity to Iso was not due either to an increased inactivation of Iso by non-neuronal cells or to a change in the thickness of the ventricle. It was found that adrenergic nerves were first capable of altering ventricular contractility on the 16th embryonic day. Whereas they interfered with the function of adrenergic nerves, injections of reserpine or 6-hydroxydopamine had no effect on the subsensitivity to Iso. Furthermore, these agents did not affect the normal developmental changes in heart weight. We conclude that the local release of transmitter from adrenergic nerves does not cause the transient subsensitivity of the ventricle of the chick embryo to beta-adrenergic agonists.
Initial Hormonal Management of Androgen-Sensitive Metastatic, Recurrent, or Progressive Prostate Cancer: 2007 Update of an American Society of Clinical Oncology Practice Guideline
Authors: D. Andrew Loblaw, Katherine S. Virgo, Robert Nam, Mark R. Somerfield, Edgar Ben-Josef, David S. Mendelson, Richard Middleton, Stewart A. Sharp, Thomas J. Smith, James Talcott, Maryellen Taplin, Nicholas J. Vogelzang, James L. Wade, Charles L. Bennett, Howard I. Scher
Journal: Journal of Clinical Oncology (2007)

To update the 2004 American Society of Clinical Oncology (ASCO) guideline on initial hormonal management of androgen-sensitive, metastatic, recurrent, or progressive prostate cancer (PCa).The writing committee based its recommendations on an updated systematic literature review. Recommendations were approved by the Expert Panel, the ASCO Health Services Committee, and the ASCO Board of Directors.Seven randomized controlled trials (four new), one systematic review, one meta-analysis (new), one Markov model, and one delta-method 95% CI procedure for active controlled trials (new) informed the guideline update.Bilateral orchiectomy or luteinizing hormone-releasing hormone agonists are recommended initial androgen-deprivation treatments (ADTs). Nonsteroidal antiandrogen monotherapy merits discussion as an alternative; steroidal antiandrogen monotherapy should not be offered. Combined androgen blockade should be considered. In metastatic or progressive PCa, immediate versus symptom-onset institution of ADT results in a moderate decrease (17%) in relative risk (RR) for PCa-specific mortality, a moderate increase (15%) in RR for non-PCa-specific mortality, and no overall survival advantage. Therefore, the Panel cannot make a strong recommendation for early ADT initiation. Prostate-specific antigen (PSA) kinetics and other metrics allow identification of populations at high risk for PCa-specific and overall mortality. Further studies must be completed to assess whether patients with adverse prognostic factors gain a survival advantage from immediate ADT. For patients electing to wait until symptoms for ADT, regular monitoring visits are indicated. For patients with recurrence, clinical trials should be considered if available. Currently, data are insufficient to support use of intermittent androgen blockade outside clinical trials
Circulating tumor cells in locally advanced pancreatic adenocarcinoma: the ancillary CirCe 07 study to the LAP 07 trial
Authors: F.C. Bidard, F. Huguet, C. Louvet, L. Mineur, O. Bouché, B. Chibaudel, P. Artru, F. Desseigne, J.B. Bachet, C. Mathiot, J.Y. Pierga, P. Hammel
Journal: Annals of Oncology (2013)
Chromosomal Changes in Syrian Hamster Cells Transformed by Simian Virus 40 (SV40) and Variants of Defective SV40 (PARA)&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Maurice Nachtigal, Joseph L. Melnick, Janet S. Butel
Journal: JNCI Journal of the National Cancer Institute (1971)

Fifteen established Syrian hamster cell lines were analyzed for their chromosome constitution. These included kidney and embryo cells transformed by simian virus 40 (SV40), lung cells which “transformed” after exposure to SV40 but did not contain SV40 tumor antigen, adult lung and kidney cells transformed by different variants of PARA (defective SV40)-adenovirus hybrid populations, and spontaneously “transformed” embryo cells. In general, chromosome abnormalities were more frequent in the cell lines transformed by PARA than in those transformed by SV40. There was an apparent predisposition of the acrocentric D group chromosomes to be involved in numerical abnormalities. Early passages of lung cells transformed by 3 nononcogenic variants of PARA-adenovirus 7 had lower incidences of dicentric chromosomes than companion cultures of lung cells transformed by oncogenic variants. Early passages of lung cells transformed by PARA-adenovirus 16 had the highest incidence of numerical and structural chromosome aberrations. Adult kidney cells transformed by oncogenic and nononcogenic variants of PARA-adenovirus 7 showed a frequency of chromosome aberrations similar to, or slightly higher than, that of SV40-transformed cells. These results suggest that adult lung cells are more prone than kidney cells to exhibit different chromosomal changes after transformation by PARA. Cells containing dicentric chromosomes were frequent in transformed cells containing SV40 tumor (T) antigen localized in the nucleus; the incidence of such cells was somewhat lower in the cell lines that did not contain detectable levels of SV40 T antigen or contained it in the cytoplasm. However, there was not always a temporal relationship between the appearance of SV40 T antigen and that of dicentric chromosomes.
Cellular Basis for the Electrocardiographic J Wave
Authors: Gan-Xin Yan, Charles Antzelevitch
Journal: Circulation (1996)

The J wave is a deflection that appears in the ECG as a late delta wave following the QRS or as a small secondary R wave (R'). Also referred to as an Osborn wave, the J wave has been observed in the ECG of animals and humans for more than four decades, yet the mechanism underlying its manifestation is poorly understood. The present study investigates the cellular basis for the J wave using an isolated arterially perfused preparation consisting of a wedge of canine right or left ventricle.A 12-lead ECG was initially recorded in vivo. After isolation and arterial perfusion of the right or left ventricular wedge, transmembrane action potentials were simultaneously recorded from epicardial, M region, and endocardial transmural sites with three floating microelectrodes. A transmural ECG was recorded concurrently. A J wave was observed at the R-ST junction of the ECG in 17 of 20 adult dogs, usually in leads II, III, aVR, and aVF and the mid to lateral precordial leads. The J wave in the transmural ECG recorded across the wedge was closely associated with the presence of a prominent action potential notch in epicardium but not endocardium. The shape and amplitude of the J wave were found to depend on (1) the transmural distribution of the action potential notch amplitude, (2) the relative time course of the early phases of the action potential (width of notch) at different sites within the wall, (3) sequence of activation, and (4) conduction time across the wall. A highly significant correlation was demonstrated between the amplitude of the epicardial action potential notch and the amplitude of the J wave recorded during interventions that alter the appearance of the electrocardiographic J wave, including hypothermia, premature stimulation, and block of the transient outward current by 4-aminopyridine. Ventricular activation from endocardium to epicardium, with epicardium activated last, was also an important prerequisite for the appearance of the J wave. This sequence permits the establishment of a voltage gradient of the early phases of the action potential after activation (ie, the QRS) is complete.Our results provide the first direct evidence in support of the hypothesis that heterogeneous distribution of a transient outward current-mediated spike-and-dome morphology of the action potential across the ventricular wall underlies the manifestation of the electrocardiographic J wave. The presence of a prominent action potential notch in epicardium but not endocardium is shown to provide a voltage gradient that manifests as a J (Osborn) wave or elevated J-point in the ECG.