tbuckley/cabot-search huggingface dataset:
Telomere Shortening and Telomerase Reverse Transcriptase Expression in Preinvasive Bronchial Lesions
Authors: Sylvie Lantuejoul, Jean Charles Soria, Luc Morat, Philippe Lorimier, Denis Moro-Sibilot, Laure Sabatier, Christian Brambilla, Elisabeth Brambilla
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Telomerase, a ribonucleoprotein complex whose activity is related to the expression of its catalytic subunit human telomerase reverse transcriptase (hTERT), restores telomere length in tumor cells and enables immortality after p53/Rb inactivation has been achieved. To determine the timing of hTERT derepression during bronchial carcinogenesis and its relationship with telomere shortening and the p53/Rb pathway alterations, we did an immunohistochemical and in situ hybridization study in preinvasive and invasive bronchial lesions. Experimental Design: hTERT, P53, P16, cyclin D1, Bax-to-Bcl2 ratio, and Ki67 immunostainings were done in 106 preneoplastic lesions and in paired lung carcinoma and normal bronchial mucosae. Concomitantly, hTERT mRNA levels and qualitative telomere shortening were assessed by in situ hybridization and fluorescence in situ hybridization, respectively, in a subset of preneoplastic and neoplastic lesions. Results: Telomerase was increasingly expressed from normal epithelium to squamous metaplasia, dysplasia, and carcinoma in situ, and decreased in invasive carcinoma (P &amp;lt; 0.0001), with a direct correlation between protein and mRNA levels of expression (P &amp;lt; 0.0001). hTERT expression was directly correlated with P53, Ki67, and Bcl2-to-Bax ratio, suggesting a coupling between telomerase reactivation, proliferation, and resistance to apoptosis. Telomere signals significantly decreased as early as squamous metaplasia and progressively increased over the spectrum of preneoplastic lesions. Conclusions: Telomere shortening represents an early genetic abnormality in bronchial carcinogenesis, preceding telomerase expression and p53/Rb inactivation, which predominate in high-grade preinvasive lesions.
DTPACE: An Effective, Novel Combination Chemotherapy With Thalidomide for Previously Treated Patients With Myeloma
Authors: Choon-Kee Lee, Bart Barlogie, Nikhil Munshi, Maurizio Zangari, Athanasios Fassas, Joth Jacobson, Frits van Rhee, Michele Cottler-Fox, Firas Muwalla, Guido Tricot
Journal: Journal of Clinical Oncology (2003)

To improve outcome in previously treated patients (at least two cycles of standard therapy) with multiple myeloma, thalidomide was combined with cytotoxic chemotherapy as induction therapy.The regimen consisted of 4-days of oral dexamethasone, daily thalidomide, and 4 days of continuous-infusion cisplatin, doxorubicin, cyclophosphamide, and etoposide (DTPACE). Response to two cycles of DTPACE for induction was evaluated in 236 patients. Before being treated with DTPACE, 148 patients (63%) had shown progressive disease while receiving standard chemotherapy, and 55 patients (23%) had chromosome 13 abnormalities.The partial remission rate (PR) after two cycles of DTPACE was 32%, with 16% attaining a complete remission (CR) or near-CR (nCR; defined as only immunofixation electrophoresis-positive). Patients with high lactate dehydrogenase (LDH; n = 98) showed a better response than those with normal LDH (n = 138): PR or better, 43% v 27% (P =.01); CR + nCR, 25% v 11% (P =.01). Patients with chromosome 13 abnormalities (n = 55) responded equally well as the other patients (n = 181): PR or better, 35% v 33% (P =.84); CR + nCR, 17% v 15% (P =.73). Patients who received 100% dose of DTPACE for two cycles (n = 115) achieved higher response rates than those with less than 100% dose (n = 121): PR or better, 49% v 17% (P <.0001); CR + nCR, 27% v 6% (P <.0001).Combination therapy of oral dexamethasone and thalidomide with infusional chemotherapy is effective as induction therapy before autotransplantation, especially in patients with high-risk features.
191. Design, Synthesis, and Characterization of a New Class of Quaternary Ammonium Gemini Amphiphiles for Gene Delivery
Authors: Qun Li, Guisheng Zhang, Wei Xu, Dexi Liu
Journal: Molecular Therapy (2006)

A series of novel quaternary ammonium Gemini amphiphiles was synthesized as a nonviral carrier for gene delivery. These amphiphiles contain a backbone of the bis(2-hydroxy-3-alkylammonio)propyl methylamine with various alkyl chains (C12 to C18) linked to two terminal amine groups. They were prepared via a bis-menshutkin reaction of the bis(2-hydroxy-3-chloropropyl)methylamine with 5M equiv of a corresponding alkyl amine (saturated or unsaturated, secondary or tertiary amines), or N, N, N|[prime]|, N|[prime]|-tetramethyl-1, 6- hexanediamine with octodecyl bromide in ethanol (75|[ndash]|80|[deg]|C, for 36|[ndash]|48h). Transfection activity of these new amphiphiles was evaluated in culture using murine melanoma BL-6, human embryonic kidney 293, HepG2 and Hela cells. We demonstrate that the transfection activity of the new compounds was dependent on the chain length of the alkyl group. Among the four cell lines tested, compounds with a relative short alky chains exhibited better transfection activity in BL-6, HepG2 and 293 cells. Cell specificity was seen in some compounds exhibiting high activity in one type of cells but minimal activity in the other. The overall transfection activity of the new compounds is comparable to that of standard transfection reagents (DOTAP/DOPE liposomes, PEI) at their optimal N/P ratio. The unique property of these new amphiphiles, especially those with short alkyl chains, is their lack of cytotoxicity to cells.
Indirect recognition of donor HLA-DR peptides in organ allograft rejection.
Authors: Z Liu, A I Colovai, S Tugulea, E F Reed, P E Fisher, D Mancini, E A Rose, R Cortesini, R E Michler, N Suciu-Foca
Journal: Journal of Clinical Investigation (1996)

To determine whether indirect allorecognition is involved in heart allograft rejection T cells obtained from peripheral blood and graft biopsy tissues were expanded in the presence of IL-2 and tested in limiting dilution analysis (LDA) for reactivity to synthetic peptides corresponding to the hypervariable regions of the mismatched HLA-DR antigen(s) of the donor. Serial studies of 32 patients showed that T cell reactivity to donor allopeptides was strongly associated with episodes of acute rejection. The frequency of allopeptide reactive T cells was 10-50-fold higher in the graft than in the periphery indicating that T cells activated via the indirect allorecognition pathway participate actively in acute allograft rejection. In recipients carrying a graft differing by two HLA-DR alleles the response appeared to target only one of the mismatched antigens of the donor. Indirect allorecognition was restricted by a single HLA-DR antigen of the host and directed against one immunodominant peptide of donor HLA-DR protein. However, intermolecular spreading was demonstrated in patients with multiple rejection episodes by showing that they develop allopeptide reactivity against the second HLA-DR antigen. These data imply that early treatment to suppress T cell responses through the indirect pathway of allorecognition, such as tolerance induction to the dominant donor determinant, may be required to prevent amplification and perpetuation of the rejection process.
A 10-s Sprint Performed After Moderate-Intensity Exercise Neither Increases nor Decreases the Glucose Requirement to Prevent Late-Onset Hypoglycemia in Individuals With Type 1 Diabetes
Authors: Raymond J. Davey, Vanessa A. Bussau, Nirubasini Paramalingam, Luis D. Ferreira, Ee Mun Lim, Elizabeth A. Davis, Timothy W. Jones, Paul A. Fournier
Journal: Diabetes Care (2013)

OBJECTIVE To determine whether performing a 10-s sprint after moderate-intensity exercise increases the amount of carbohydrate required to maintain euglycemia and prevent late-onset postexercise hypoglycemia relative to moderate-intensity exercise alone. RESEARCH DESIGN AND METHODS Seven individuals with type 1 diabetes underwent a hyperinsulinemic-euglycemic clamp and performed 30 min of moderate-intensity exercise on two separate occasions followed by either a 10-s maximal sprint effort or no sprint. During the following 8 h, glucose infusion rate to maintain euglycemia and rates of glucose appearance and disappearance were measured continuously. RESULTS In response to exercise and throughout the 8-h recovery period, there were no differences in glucose infusion rate, blood glucose levels, plasma insulin concentrations, and rates of glucose appearance and disappearance between the two experimental conditions (P &amp;gt; 0.05). CONCLUSIONS A 10-s sprint performed after 30 min of moderate-intensity exercise does not affect the amount of carbohydrate required to maintain euglycemia postexercise in individuals with type 1 diabetes.
Complication Rate of Right Ventricular Endomyocardial Biopsy via the Femoral Approach
Authors: Matthias Holzmann, Alexander Nicko, Uwe Kühl, Michel Noutsias, Wolfgang Poller, Wolfgang Hoffmann, Andreas Morguet, Bernhard Witzenbichler, Carsten Tschöpe, Heinz-Peter Schultheiss, Matthias Pauschinger
Journal: Circulation (2008)

An unequivocal diagnosis of myocarditis and cardiac virus persistence is based on histological, immunohistological, and molecular biological analyses of endomyocardial biopsies (EMBs). Biopsy-based diagnosis of myocarditis has become increasingly important because recent studies have demonstrated the beneficial effects of biopsy-based causal treatment strategies (immunosuppressive or antiviral). Because the risks of major complications caused by EMB procedures have not yet been well defined, we evaluated the incidence of major and minor complications of right ventricular EMB procedures in this retrospective and prospective single-center study.With the use of a modified Cordis bioptome, 1919 patients underwent 2505 EMB procedures retrospectively over a 9-year period (January 1995 to December 2003), and 496 patients underwent 543 EMB procedures prospectively between January 2004 and December 2005. A total of 2415 patients had 3048 EMB procedures via the right femoral vein approach under biplane fluoroscopic control to evaluate unexplained left ventricular dysfunction (retrospective left ventricular ejection fraction, 49.8+/-18.8%; prospective, 48.8+/-19.7%) after exclusion of secondary causes. During each EMB procedure, an average of 8.2+/-0.8 EMBs were obtained retrospectively and 10.1+/-0.6 specimens prospectively for a total of 26 025 specimens. No patient died or required emergency cardiac surgery. Other major complications like cardiac tamponade requiring pericardiocentesis or complete atrioventricular block requiring permanent pacing were very rare: 0.12% in the retrospective study and 0% in the prospective study. Minor complications such as pericardial effusion, conduction abnormalities, or arrhythmias occurred in 0.20% of the EMB procedures in the retrospective study and 5.5% in the prospective study.The EMB procedure via the femoral vein approach under fluoroscopic guidance has a very low complication rate when performed by experienced operators.
Circulating Transforming Growth Factor-β in Marfan Syndrome
Authors: Peter Matt, Florian Schoenhoff, Jennifer Habashi, Tammy Holm, Christel Van Erp, David Loch, Olga D. Carlson, Benjamin F. Griswold, Qin Fu, Julie De Backer, Bart Loeys, David L. Huso, Nazli B. McDonnell, Jennifer E. Van Eyk, Harry C. Dietz
Journal: Circulation (2009)

Background— Marfan syndrome (MFS) is caused by mutations in the fibrillin-1 gene and dysregulation of transforming growth factor-β (TGF-β). Recent evidence suggests that losartan, an angiotensin II type 1 blocker that blunts TGF-β activation, may be an effective treatment for MFS. We hypothesized that dysregulation of TGF-β might be mirrored in circulating TGF-β concentrations. Methods and Results— Serum obtained from MFS mutant mice ( Fbn1 C1039G /+ ) treated with losartan was analyzed for circulating TGF-β1 concentrations and compared with those from placebo-treated and wild-type mice. Aortic root size was measured by echocardiography. Data were validated in patients with MFS and healthy individuals. In mice, circulating total TGF-β1 concentrations increased with age and were elevated in older untreated Fbn1 C1039G /+ mice compared with wild-type mice ( P =0.01; n=16; mean±SEM, 115±8 ng/mL versus n=17; mean±SEM, 92±4 ng/mL). Losartan-treated Fbn1 C1039G /+ mice had lower total TGF-β1 concentrations compared with age-matched Fbn1 C1039G /+ mice treated with placebo ( P =0.01; n=18; 90±5 ng/mL), and circulating total TGF-β1 levels were indistinguishable from those of age-matched wild-type mice ( P =0.8). Correlation was observed between circulating TGF-β1 levels and aortic root diameters in Fbn1 C1039G /+ and wild-type mice ( P =0.002). In humans, circulating total TGF-β1 concentrations were elevated in patients with MFS compared with control individuals ( P &lt;0.0001; n=53; 15±1.7 ng/mL versus n=74; 2.5±0.4 ng/mL). MFS patients treated with losartan (n=55) or β-blocker (n=80) showed significantly lower total TGF-β1 concentrations compared with untreated MFS patients ( P ≤0.05). Conclusions— Circulating TGF-β1 concentrations are elevated in MFS and decrease after administration of losartan, β-blocker therapy, or both and therefore might serve as a prognostic and therapeutic marker in MFS.
Studies of carcinogenicity of sodium chlorite in B6C3F1 mice.
Authors: Y Yokose, K Uchida, D Nakae, K Shiraiwa, K Yamamoto, Y Konishi
Journal: Environmental Health Perspectives (1987)

The carcinogenic activities of sodium chlorite in B6C3F1 mice were examined. Sodium chlorite was given at concentrations of 0 (control), 0.025% (low dose), or 0.05% (high dose) in the drinking water of 150 female and 150 male mice for 80 weeks, after which time the animals were returned to distilled water without sodium chlorite. All mice were sacrificed 85 weeks from the beginning of the experiment. The incidence of tumor-bearing animals was 32% (control), 34% (low dose), and 26% (high dose) in female mice, and 46% (control), 57% (low dose), and 53% (high dose) in male mice. The types and incidence of neoplasms that occurred frequently in each group of both sexes were similar to those observed spontaneously in B6C3F1 mice. The incidence of lymphomas/leukemias in the high dose group of females (2%), however, was lower than that in the control group (15%). Furthermore, the incidence of pulmonary adenomas in the high dose group of males (12%) was higher than that in the control group (0%), but neither dose-related increases in the adenoma incidences nor increased incidences of the adenocarcinomas were observed. These results indicated no clear evidence of a carcinogenic potential of sodium chlorite in B6C3F1 mice.
REACTION OF I-131 TRACE LABELED HUMAN ANTI-RH0(D) WITH RED CELLS*†
Authors: S. P. Masouredis
Journal: Journal of Clinical Investigation (1959)

nell, Coombs and Rizk (11) appreciated the pos- sibilities offered by the I-13 1 protein label and tagged human anti-Rho(D) serum.They were able to use the labeled isoantibody to estimate the number of Rho (D) sites and the Paul-Bunnell sites on the red cell, and more recently the anti- gen sites on the rabbit red cell (12).Melcher, Steinfeld and Reed (13), using both I-131 sheep red cell agglutinating rabbit serum and an I-131 incomplete red cell antibody, obtained from a patient with acquired hemolytic anemia, were able to show by zone electrophoresis that the red cell isoantibody activity was associated with the gamma globulin fraction.Although these studies established the useful- ness of I-131 labeled red cell isoantibodies, they were severely limited by the binding of nonspecific I-131 labeled proteins to the red cells.The prob- lem of nonspecific binding of labeled proteins to red cells was re-examined in this report.The studies to be presented have shown that by the use of alcohol fractionation and elution techniques an I-131 trace labeled anti-Rho(D) can be ob- tained that reacts specifically with Rho(D) posi- tive red cells. MATERIALS AND METHODSFractionation of anti-Rho(D) plasma.High titered anti-Rho(D) plasma was obtained from a 30 year old white housewife who had been immunized to Rho(D) by eight pregnancies.The last nonviable delivery occurred in February, 1955, at which time she had both Fallopian tubes ligated.Her phenotype was A2, rh (cde), and her serum contained an incomplete anti-Rho(D) with a titer of 64.She was injected intravenously with 1 ml. of type Al, Rho(cDe) blood and phlebotomized 13 days later (14-16).The blood was collected by means of an ion-ex- change plastic donor set that contained Dowex 50.At this time her serum incomplete anti-Rho(D) titer was 8,192.The specificity of the antibody was anti-Rho(D) as determined by the anti-globulin reaction and a panel of known red cells (Panocell®, Knickerbocker, New York, N. Y.).
Proposal Seeks to Enhance Availability of Clinical Trial Results
Authors: Tracy Hampton
Journal: JAMA (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA 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
CD4 Regulates Susceptibility to Fas ligand– and Tumor Necrosis Factor–mediated Apoptosis
Authors: Alicia Algeciras, David H. Dockrell, David H. Lynch, Carlos V. Paya
Journal: The Journal of Experimental Medicine (1998)

The current knowledge of CD4 function is limited to its role as a necessary coreceptor in TCR-initiated signaling. We have investigated whether CD4 regulates additional T cell functions. Using human primary resting CD4+ T cells, we demonstrate that CD4 activation is sufficient to induce lymphocyte death. Immediately after CD4 cross-linking, CD4+ T cells are rendered susceptible to apoptosis mediated by TNF or FasL. This, together with the concomitant induction of FasL within the same population, results in significant CD4+ T cell death in vitro. The CD4-dependent induction of susceptibility to apoptosis that is mediated by TNF or FasL is protein synthesis independent but phosphorylation dependent. After CD4 activation, PKC regulates susceptibility to apoptosis mediated by FasL but not the induction of susceptibility to TNF-dependent apoptosis. Moreover, significant differences between CD3 and CD4 activation were observed with regards to the kinetics of induction of CD4+ T cell susceptibility to FasL- and TNF-mediated apoptosis. Altogether, these results provide a model with which to study the molecular mechanisms regulating lymphocyte survival after CD4 activation, and highlight the potential role of CD4 in controlling lymphocyte apoptosis under physiological conditions or in disease states such as HIV infection.
Congress Authorizes Construction Funds For Mouse Research Laboratory
Authors: Elaine Blume
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article Congress Authorizes Construction Funds For Mouse Research Laboratory Get access Elaine Blume Elaine Blume Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 1, 3 January 1990, Page 13, https://doi.org/10.1093/jnci/82.1.13 Published: 03 January 1990
Trophism versus Tropism
Authors: Robert W. Buck, Maxwell Finland, Hudson Hoagland
Journal: New England Journal of Medicine (1952)

The following communications are published in this department rather than under Correspondence because of their peculiar etymologic significance. It is hoped that they may serve in some measure to settle the mild controversy that has refused to rage over the correct derivation and consequently the spelling of the first of the two words commonly abbreviated, after the modern alphabetical fashion into ACTH.It is understood that the root trophic bears no relation to the Latin trophaeum (from the Greek tropaion), referring originally to a monument of the enemy's defeat. With or without trophies, the present decision seems to point . . .
Cutaneous malignant fibrous histiocytoma of the scalp in a renal transplant recipient
Authors: A. Stein, I. Hackert, G. Sebastian, M. Meurer
Journal: British Journal of Dermatology (2005)

Journal Article Cutaneous malignant fibrous histiocytoma of the scalp in a renal transplant recipient Get access A. Stein, A. Stein Department of Dermatology, University Hospital of the Technical University, Fetscherstraße 74, 01307 Dresden, Germany E‐mail: steina@rcs.urz.tu‐dresden.de Search for other works by this author on: Oxford Academic Google Scholar I. Hackert, I. Hackert Department of Dermatology, University Hospital of the Technical University, Fetscherstraße 74, 01307 Dresden, Germany E‐mail: steina@rcs.urz.tu‐dresden.de Search for other works by this author on: Oxford Academic Google Scholar G. Sebastian, G. Sebastian Department of Dermatology, University Hospital of the Technical University, Fetscherstraße 74, 01307 Dresden, Germany E‐mail: steina@rcs.urz.tu‐dresden.de Search for other works by this author on: Oxford Academic Google Scholar M. Meurer M. Meurer Department of Dermatology, University Hospital of the Technical University, Fetscherstraße 74, 01307 Dresden, Germany E‐mail: steina@rcs.urz.tu‐dresden.de Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 154, Issue 1, 1 January 2006, Pages 183–185, https://doi.org/10.1111/j.1365-2133.2005.06990.x Published: 01 January 2006
Eplerenone and new‐onset diabetes in patients with mild heart failure: results from the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS‐HF)
Authors: David Preiss, Dirk J. van Veldhuisen, Naveed Sattar, Henry Krum, Karl Swedberg, Harry Shi, John Vincent, Stuart J. Pocock, Bertram Pitt, Faiez Zannad, John J.V. McMurray
Journal: European Journal of Heart Failure (2012)