tbuckley/cabot-search huggingface dataset:
p160 Bcr Mediates Platelet-Derived Growth Factor Activation of Extracellular Signal-Regulated Kinase in Vascular Smooth Muscle Cells
Authors: Wenyi Che, Jun-ichi Abe, Masanori Yoshizumi, Qunhua Huang, Michael Glassman, Shinsuke Ohta, Matthew G. Melaragno, Veronica Poppa, Chen Yan, Nicole Lerner-Marmarosh, Changxi Zhang, Yun Wu, Ralph Arlinghaus, Bradford C. Berk
Journal: Circulation (2001)

The human Bcr gene was originally identified by its presence in the chimeric Bcr/Abl oncogene, which is causative for chronic myeloblastic leukemia. Because Bcr encodes a serine/threonine protein kinase, we studied its kinase activity and determined the role of Bcr in the PDGF signaling pathway to ERK1/2 activation and DNA synthesis in rat aortic smooth muscle cells (RASMCs).In RASMCs, platelet-derived growth factor-BB (PDGF) stimulated Bcr kinase activity, with a maximum at 1 minute. Because phosphatidylinositol 3'-kinase (PI3-K) is essential for Bcr/Abl leukemogenesis, we evaluated the role of mouse PDGF-beta-receptor binding sites for PI3-K (Y708, Y719) and for phospholipase C-gamma (Y977, Y989) in PDGF-mediated Bcr kinase activation. The mutant PDGF receptor Y708F/Y719F but not Y977F/Y989F showed significantly reduced Bcr kinase activity. To determine the role of Bcr in PDGF-mediated signal transduction events leading to ERK1/2 and its downstream Elk1 transcription activation, wild-type (WT) and kinase-negative (KN) Bcr were transiently expressed in RASMCs. Bcr WT enhanced, whereas Bcr KN inhibited, PDGF-stimulated ERK1/2 and Elk1 transcriptional activity. Overexpression of Bcr also enhanced PDGF-induced Ras/Raf-1 activity and DNA synthesis, but this regulation is independent of the kinase activity of Bcr. Finally, we found that Bcr expression was increased in the neointimal layer after balloon injury of rat carotid artery.These results demonstrated the importance of Bcr in PDGF-mediated events, such as activation of Ras, Raf-1, ERK1/2, and Elk1, and stimulation of DNA synthesis.
<b> <i>SEL1L</i> </b> and Squamous Cell Carcinoma of the Esophagus
Authors: Paola Granelli, Monica Cattaneo, Stefano Ferrero, Luca Bottiglieri, Silvano Bosari, Giuseppe Fichera, Ida Biunno
Journal: Clinical Cancer Research (2004)

Abstract The gene SEL1L is involved both in human breast and pancreatic cancer progression. It is located on 14q24.3–31, a region known to be lost in invasive cancer of the esophagus. We aimed to assess whether SEL1L could become a useful biomarker for this cancer. We assessed SEL1L mRNA and protein expression in 35 patients and found it to be weak in low-grade and strong in high-grade dysplasia. Although the majority of cancer patients showed differential expression (mRNA and protein) of SEL1L, in five cases it was completely absent; these patients had the worst outcomes. SEL1L immunoreactivity was negative in normal tissue samples from five patients with mild esophagitis as well as in normal mucosa adjacent to the tumor. We hypothesize that SEL1L could influence those cellular changes that mediate the transition from a normal mucosa to a neoplastic lesion and may help in the identification of those patients at higher risk of developing this cancer. The specific impact of SEL1L in esophageal cancer needs further investigation.
In vivo influx of free and esterified plasma cholesterol into human aortic tissue without atherosclerotic lesions.
Authors: S Stender, E Hjelms
Journal: Journal of Clinical Investigation (1984)

In order to determine the in vivo influx of plasma cholesterol into human aortic intimamedia tissue, specimens of the ascending aortic wall without visible atherosclerosis were obtained from patients undergoing aortic valve replacement. Before the operation the patients were intravenously injected with autologous plasma in which the lipoproteins were labeled with radioactive cholesterol. The influence of the duration of the exposure time (0.3-114 h) and of the distribution of radioactivity between free and esterified cholesterol in plasma on the amount of radioactivity found in the arterial wall was studied by the simultaneous use of 3H- and 14C-cholesterol. It was shown that the influx of free and esterified cholesterol into the intima-media layer of the tissue could be calculated from a set of linear equations that relate the labeled sterols in the tissue to the average specific activities in plasma. In nine patients between 50 and 70 yr of age with 4.2-5.9 mM total cholesterol in plasma, the influx of free cholesterol and of esterified cholesterol was 1.2-8.8 and 1.0-12.5 nmol X cm-2 X d-1, respectively. Both hydrolysis and esterification of the sterol fractions in the aortic tissue and exchange of free cholesterol between the plasma lipoproteins and the tissue were demonstrated. The cholesterol content of the intima-media layer was 0.6-2.3 mumol X cm-2. This corresponds to the influx of esterified cholesterol during a period of only 0.1-3.5 yr, which is short compared with the lifespan of the patient. Our data thus suggest that removal of esterified cholesterol from aortic tissue without visible atherosclerosis represents a major importance for the cholesterol concentration in the tissue.
Factors affecting the autologous mixed lymphocyte reaction in kidney transplantation.
Authors: L Fuller, C Flaa, D Jaffe, J Strauss, G K Kyriakides, J Miller
Journal: Journal of Clinical Investigation (1983)

In long-term well adapted kidney transplant recipients we have found a close correlation between the T helper (TH):T suppressor/cytotoxic (TS/C) subset ratios and the presence of T cells that respond in the autologous mixed lymphocyte reaction (AMLR). In 21 recipients with T cell E rosette levels ranging between 53 and 86% and TH:TS/C ratios between 0.15 to 2.10, ratios of greater than 0.8 correlated with AMLR responses (13/13), and ratios of less than 0.8 with AMLR nonreactivity (7/7). By contrast, the allogeneic MLR showed no apparent correlation with the TH:TS/C ratios or with the AMLR pre- or postoperatively. It was found that the AMLR in 22 of 23 normal individuals was markedly inhibited by autologous T cells obtained from peripheral blood lymphocytes, exposed to 3,000 rad (Tx) and added as a third component to the cultures. In contrast, 13 of 13 kidney transplant recipients failed to exhibit this Tx AMLR inhibitory cell population. The "naturally occurring" T inhibitory cells, fractionated by an affinity column chromatography procedure into x-irradiated TH and TS/C subsets, inhibited the AMLR to the same extent as unseparated Tx cells. In cell interchange studies performed in four of five HLA identical donor-recipient pairs the Tx cells of the (normal) donor inhibited the recipient AMLR (immunosuppressed), but recipient Tx cells failed to inhibit the donor AMLR. Finally T cells, primed in AMLR and allogeneic MLR for 10 d were tested for AMLR or allogeneic MLR inhibitory activity. Allogeneic MLR primed x-irradiated cells, inhibited both the AMLR and allogeneic MLR while AMLR x-irradiated primed cells inhibited neither reaction. The Tx AMLR inhibitor found in normal peripheral blood, appears to be a cell that is highly sensitive to the effects of biologic or pharmacologic immunosuppressive agents.
Laboratory markers in IBD: useful, magic, or unnecessary toys?
Authors: S Vermeire
Journal: Gut (2006)

Laboratory markers have been investigated in inflammatory bowel disease (IBD) for diagnostic and differential diagnostic purposes, for assessment of disease activity and risk of complications, for prediction of relapse, and for monitoring the effect of therapy. The introduction of biological therapies in IBD has renewed interest in inflammatory markers (especially C reactive protein (CRP)), given their potential to select responders to these treatments. Of all the laboratory markers, CRP is the most studied and has been shown to have the best overall performance. CRP is an objective marker of inflammation and correlates well with disease activity in Crohn's disease (CD). Increased CRP levels are associated with better response rates and normal CRP levels predict high placebo response rates in clinical trials with biologicals. However, despite the advantages of CRP over other markers, it is still far from ideal. Furthermore, CRP correlates less well with disease activity in patients with ulcerative colitis (UC) as compared with CD. Other laboratory markers, including erythrocyte sedimentation rate (ESR), leucocyte and platelet count, albumin, and 1 acid glycoprotein (orosomucoid), have been studied either less extensively in IBD or have proven to be less useful than CRP. Faecal markers seem promising and may be more specific in detecting gut inflammation in patients with established IBD. Promising results have been reported with the use of faecal calprotectin in CD as well as in UC. Recent data however suggest that the performance of the faecal calprotectin test is superior for UC than for CD. Taken together, laboratory markers are useful and should be part of the global management of our IBD patients. They are however not magic and until more data become available, the use of CRP and other laboratory markers should be seen as an additive tool to clinical observation and physical examination rather than a replacement.
Idiopathic portal hypertension (perisinusoidal fibrosis) after renal transplantation.
Authors: C Nataf, G Feldmann, D Lebrec, C Degott, J M Descamps, B Rueff, J P Benhamou
Journal: Gut (1979)

We report the cases of two renal transplant recipients suffering from idopathic portal hypertension, a condition characterised by increased portal venous pressure in the absence of both histological lesion of the liver and obstruction of the portal vein. In these two patients, perisnusoidal fibrosis, invisible by light microscopy, was demonstrated by electron microscopy; it is suggested that partial obstruction of hepatic sinusoids by perisinusoidal fibrosis could be the mechanism for increased portal venous pressure in all the patients with idiopathic portal hypertension. In these two patients, who received 6-mercaptopurine and azathioprine, perisinusoidal fibrosis might be the consequence of prolonged administration of these drugs.
Optimizing the Use of Pneumococcal Conjugate Vaccine Globally
Authors: Katherine L. O’Brien
Journal: JAMA (2013)

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
Impact of Young Age on Treatment Efficacy and Safety in Advanced Colorectal Cancer: A Pooled Analysis of Patients From Nine First-Line Phase III Chemotherapy Trials
Authors: Charles D. Blanke, Brian M. Bot, David M. Thomas, Archie Bleyer, Claus-Henning Kohne, Matthew T. Seymour, Aimery de Gramont, Richard M. Goldberg, Daniel J. Sargent
Journal: Journal of Clinical Oncology (2011)

Purpose Colorectal cancer predominantly occurs in the elderly, but approximately 5% of patients are 50 years old or younger. We sought to determine whether young age is prognostic, or whether it influences efficacy/toxicity of chemotherapy, in patients with advanced disease. Methods We analyzed individual data on 6,284 patients from nine phase III trials of advanced colorectal cancer (aCRC) that used fluorouracil-based single-agent and combination chemotherapy. End points included progression-free survival (PFS), overall survival (OS), response rate (RR), and grade 3 or worse adverse events. Stratified Cox and adjusted logistic-regression models were used to test for age effects and age-treatment interactions. Results A total of 793 patients (13%) were younger than 50 years old; 188 of these patients (3% of total patients) were younger than 40 years old. Grade 3 or worse nausea (10% v 7%; P = .01) was more common, and severe diarrhea (11% v 14%; P = .001) and neutropenia (23% v 26%; P &lt; .001) were less common in young (younger than 50 years) than in older (older than 50 years) patients. Age was prognostic for PFS, with poorer outcomes occurring in those younger than 50 years (median, 6.0 v 7.5 months; hazard ratio, 1.10; P = .02), but it did not affect RR or OS. In the subset of monotherapy versus combination chemotherapy trials, the relative benefits of multiagent chemotherapy were similar for young and older patients. Results were comparable when utilizing an age cut point of 40 years. Conclusion Young age is modestly associated with poorer PFS but not OS or RR in treated patients with aCRC, and young patients have more nausea but less diarrhea and neutropenia with chemotherapy in general. Young versus older patients derive the same benefits from combination chemotherapy. Absent results of a clinical trial, standard combination chemotherapy approaches are appropriate for young patients with aCRC.
Parent Opinions Regarding the Genetic Testing of Minors for <i>BRCA1/2</i>
Authors: Angela R. Bradbury, Linda Patrick-Miller, Brian Egleston, Colleen Burke Sands, Tianyu Li, Helen Schmidheiser, Maia Feigon, Comfort N. Ibe, Fay J. Hlubocky, Kisha Hope, Sarah Jackson, Melanie Corbman, Olufunmilayo I. Olopade, Mary Daly, Christopher K. Daugherty
Journal: Journal of Clinical Oncology (2010)

Although not currently recommended, genetic testing of minors for adult hereditary cancer syndromes, along with risks and benefits, is still being debated. Thus, we evaluated parent opinions regarding BRCA1/2 testing of minors, in general, and hypothetically, for parents' own minor child.Semistructured interviews were conducted to assess parent opinions regarding BRCA1/2 testing in minors, along with parent rationale for and factors associated with these opinions.In total, 246 parents at two academic cancer risk assessment programs who underwent BRCA1/2 testing completed the interview (60% response rate). In response to a dichotomous question, 37% of parents supported testing minors. Responses to an open-ended query suggest that 47% support testing minors in some or all circumstances. Parent negative BRCA1/2 test result (P = .02), parent male sex (P = .03), and minority race (P = .01) were independently associated with support of testing minors. In response to a dichotomous question, 44% of parents reported hypothetical interest in testing their own minor offspring. Responses to an open-ended query suggest that 55% would consider, hypothetically, testing their child in some or all circumstances. Parent negative test result (P = .01), less than a college education (P < .01), and older mean offspring age (P = .05) were associated with interest in testing one's own child.Parents' opinions regarding BRCA1/2 testing of minors are divided. Given the lack of evidence supporting either the permission or restriction of BRCA1/2 testing in minors, further evaluation of the risks and benefits of providing genetic risk information and genetic testing to minors for adult-onset disease is needed to inform clinical practice and guidelines.
A common cell-type specific surface antigen in cultured human glial cells and fibroblasts: loss in malignant cells.
Authors: A Vaheri, E Ruoslahti, B Westermark, J Ponten
Journal: The Journal of Experimental Medicine (1976)

Fibroblast surface antigen (SFA) is a high molecular weight protein antigen, first shown on the surface of cultured fibroblasts in fibrillar structures. It is shed to the extracellular medium and also present in the circulation (serum and plasma). Fibroblasts transformed by tumor viruses produce SFA but do not retain it on cell surface. In this report we show that SFA is also present in cultured nonestablished astroglial cells. The glial and fibroblast SFAs are immunologically indistinguishable. Glial cells (three different nonestablished lines) contain more SFA per milligram cellular protein than fibroblasts. SFA was located on cell surface in fibrillar striae that frequently extended out from the cell body. Fluorescence was also found intracellularly in the cytoplasm. Malignant gliomas (astrocytomas) established to grow in culture from human tumor material produced SFA into the growth medium but had very little (lines U-105 MG and U-343 MG) or no detectable (lines U-118 MG, U-251 MG, and U-343 MG-a) cell surface SFA. In cultures of the glioma cells many cells, in particular those that appeared to be in the telophase stage, stained strongly positive for intracellular cytoplasmic SFA. These data demonstrate that similar to fibroblasts transformed experimentally by oncogenic viruses, cells grown from naturally occurring human tumors (glioblastomas) produce SFA but lose ability to retain it on cell surface.
Comparison of storage phosphor computed radiography with conventional film-screen radiography in the recognition of pneumoconiosis
Authors: A.S. Laney, E.L. Petsonk, A.L. Wolfe, M.D. Attfield
Journal: European Respiratory Journal (2009)

Traditional film-screen radiography (FSR) has been useful in the recognition and evaluation of interstitial lung diseases, but is becoming increasingly obsolete. To evaluate the applicability of storage phosphor digital computed radiography (CR) images in the recognition of small lung opacities, we compared image quality and the profusion of small opacities between FSR and CR radiographs. We screened 1,388 working coal miners during the course of the study with FSR and CR images obtained on the same day from all participants. Each traditional chest film was independently interpreted by two of eight experienced readers using the International Labour Office (ILO) classification of radiographs of pneumoconiosis, as were CR images displayed on medical-grade computer monitors. The prevalence of small opacities (ILO category 1/0 or greater) did not differ between the two imaging modalities (5.2% for FSR and 4.8% for soft copy CR; p&gt;0.50). Inter-reader agreement was also similar between FSR and CR. Significant differences between image modalities were observed in the shape of small opacities, and in the proportion of miners demonstrating high opacity profusion (category 2/1 and above). Our results indicate that, with appropriate attention to image acquisition and soft copy display, CR digital radiography can be equivalent to FSR in the identification of small interstitial lung opacities.
Cytotoxic T cell responses to multiple conserved HIV epitopes in HIV-resistant prostitutes in Nairobi.
Authors: S L Rowland-Jones, T Dong, K R Fowke, J Kimani, P Krausa, H Newell, T Blanchard, K Ariyoshi, J Oyugi, E Ngugi, J Bwayo, K S MacDonald, A J McMichael, F A Plummer
Journal: Journal of Clinical Investigation (1998)

Many people who remain persistently seronegative despite frequent HIV exposure have HIV-specific immune responses. The study of these may provide information about mechanisms of natural protective immunity to HIV-1. We describe the specificity of cytotoxic T lymphocyte responses to HIV in seronegative prostitutes in Nairobi who are apparently resistant to HIV infection. These women have had frequent exposure to a range of African HIV-1 variants, primarily clades A, C, and D, for up to 12 yr without becoming infected. Nearly half of them have CTL directed towards epitopes previously defined for B clade virus, which are largely conserved in the A and D clade sequences. Stronger responses are frequently elicited using the A or D clade version of an epitope to stimulate CTL, suggesting that they were originally primed by exposure to these virus strains. CTL responses have been defined to novel epitopes presented by HLA class I molecules associated with resistance to infection in the cohort, HLA-A*6802 and HLA-B18. Estimates using a modified interferon-gamma Elispot assay indicate a circulating frequency of CTL to individual epitopes of between 1:3,200 and 1:50,000. Thus, HIV-specific immune responses-particularly cross-clade CTL activity- may be responsible for protection against persistent HIV infection in these African women.
THE MECHANISM OF THE CURATIVE ACTION OF ANTIPNEUMOCOCCUS SERUM
Authors: Carroll G. Bull
Journal: The Journal of Experimental Medicine (1915)

An active antipneumococcus serum causes agglutination of pneumococci in vitro and in vivo. The antiserum acts in far greater dilution in causing agglutination as determined by the microscopic than by the macroscopic test. The antiserum when injected into the circulation of rabbits suffering from pneumococcus bacteremia causes a rapid disappearance of the diplococci from the blood. This disappearance is brought about by instantaneous clumping of the diplococci in vivo and the removal of the clumps by the liver, spleen, lungs, and possibly other organs.
Characterization of Human Neuroblastoma Cell Lines Established Before and After Therapy&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: C P Reynolds, J L Biedler, B A Spengler, D A Reynolds, R A Ross, E P Frenkel, R G Smith
Journal: JNCI Journal of the National Cancer Institute (1986)

Journal Article Characterization of Human Neuroblastoma Cell Lines Established Before and After Therapy Get access C. P. Reynolds, C. P. Reynolds Search for other works by this author on: Oxford Academic PubMed Google Scholar J. L. Biedler, J. L. Biedler Search for other works by this author on: Oxford Academic PubMed Google Scholar B. A. Spengler, B. A. Spengler Search for other works by this author on: Oxford Academic PubMed Google Scholar D. A. Reynolds, D. A. Reynolds Search for other works by this author on: Oxford Academic PubMed Google Scholar R. A. Ross, R. A. Ross Search for other works by this author on: Oxford Academic PubMed Google Scholar E. P. Frenkel, E. P. Frenkel Search for other works by this author on: Oxford Academic PubMed Google Scholar R. G. Smith R. G. Smith Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 76, Issue 3, March 1986, Pages 375–387, https://doi.org/10.1093/jnci/76.3.375 Published: 01 March 1986 Article history Received: 17 July 1984 Accepted: 12 November 1985 Published: 01 March 1986