tbuckley/cabot-search huggingface dataset:
EGF Receptor Activity Modulates Apoptosis Induced by Inhibition of the Proteasome of Vascular Smooth Muscle Cells
Authors: Wei-Zhong Ying, Huang-Ge Zhang, Paul W. Sanders
Journal: Journal of the American Society of Nephrology (2006)

The observation that intracellular protein turnover rates participate directly in cell viability led to the development and clinical use of potent proteasome inhibitors. This study determined that the mechanism of apoptosis that is induced by inhibition of the proteasome of vascular smooth muscle cells (VSMC) was related to the intracellular accumulation of Bad, a BH3-only member of the Bcl-2 family of apoptosis regulators. Experiments confirmed that the apoptotic process was mitochondria- and caspase-dependent. Ubiquitination and accumulation of Bad in VSMC followed inhibition of the proteasome, and depletion of Bad using RNA interference prevented apoptosis that was induced by proteasome inhibition with PS-341. EGF receptor (EGFR) activation produced posttranslational modifications of Bad, providing the pro-survival signals that prevented apoptosis of smooth muscle cells during proteasome inhibition. Antagonists of the EGFR potentiated the apoptotic rate. In summary, the activities of the EGFR and the proteasome focused on Bad and the intrinsic apoptotic pathway and were involved integrally in determining viability of VSMC. These findings might prove useful in the management of diseases in which proliferation of vascular smooth muscle cells plays a central role.
Adjunctive 17β-estradiol administration reduces infarct size by altered expression of canine myocardial connexin43 protein
Authors: T LEE, M LIN, T CHOU, C TSAI, N CHANG
Journal: Cardiovascular Research (2004)

Traffic of potentially harmful cytosolic messengers through gap junctions might cause increased injury during ischemia. The present study was to determine whether the infarct size-reducing effect of adjunctive estradiol administration prior to reperfusion is associated with an attenuated expression of connexin43 at the border of infarction in a canine model.Experiments were performed in 48 dogs (n=16 each group), assigned to receive either vehicle (control group), 17beta-estradiol administered before coronary occlusion (early group), or 3 min before coronary reperfusion following 60-min ischemia (late group). Changes in the amount of phosphorylated connexin43 were measured by Western blot.Infarct size was significantly larger in the control (38+/-7% of area at risk) than in the supplemented groups (16+/-6% in the early group; 16+/-8% in the late group, P<0.0001, both). Reperfusion caused a significant elevation in free radicals as measured by lucigenin-derived chemiluminescence. The rise of free radicals was significantly inhibited in animals treated with estrogen, either early or late. The amount of phosphorylated connexin43 was reduced, as assessed by Western blot in control hearts at the border zone. These changes were significantly enhanced by estrogen administration. The magnitude of infarct size positively correlated with the magnitude of phosphorylated connexin43 expression assessed by Western blot (r=0.83, P<0.0001). Confocal microscopy confirmed the changes of junctional complexes.This result demonstrated that the cardioprotective effect of estrogen as an antioxidant may be associated with the reduced amount of phosphorylated myocardial connexin43 protein.
Distribution of metastatic sites in renal cell carcinoma: a population-based analysis
Authors: M. Bianchi, M. Sun, C. Jeldres, S.F. Shariat, Q.-D. Trinh, A. Briganti, Z. Tian, J. Schmitges, M. Graefen, P. Perrotte, M. Menon, F. Montorsi, P.I. Karakiewicz
Journal: Annals of Oncology (2011)
The in vitro diagnosis of drug allergy: status and perspectives
Authors: D. G. Ebo, J. Leysen, C. Mayorga, A. Rozieres, E. F. Knol, I. Terreehorst
Journal: Allergy (2011)

To cite this article: Ebo DG, Leysen J, Mayorga C, Rozieres A, Knol EF, Terreehorst I. The in vitro diagnosis of drug allergy: status and perspectives. Allergy 2011; 66: 1275–1286. Adverse drug reactions (ADR) can result from immune-mediated (drug allergy) and nonimmune-mediated mechanisms. In both types of reaction, conclusive diagnosis and appropriate management remain major problems in daily clinical practice. This review summarizes the potentials and shortcomings of the currently available in vitro tests in the diagnosis of immediate (mostly IgE mediated) and nonimmediate (mostly T-cell mediated) drug allergy, particularly quantification of specific IgE, flow-assisted analysis of in vitro activated lymphocytes and basophils and the enzyme-linked immunosorbent spot.
Quality of Care for Patients Diagnosed With Diabetes at Screening
Authors: David Edelman, Maren K. Olsen, Tara K. Dudley, Amy C. Harris, Eugene Z. Oddone
Journal: Diabetes Care (2003)

Screening for diabetes has the potential to be an effective intervention, especially if patients have intensive treatment of their newly diagnosed diabetes and comorbid hypertension. We wished to determine the process and quality of diabetes care for patients diagnosed with diabetes by systematic screening.A total of 1,253 users of the Durham Veterans Affairs Medical Center aged 45-64 years who did not report having diabetes were screened for diabetes with an HbA(1c) test. All subjects with an HbA(1c) level > or =6.0% were invited for follow-up blood pressure and fasting plasma glucose (FPG) measurements. A case of unrecognized diabetes was defined as HbA(1c) > or =7.0% or FPG > or =126 mg/dl. For each of the 56 patients for whom we made a new diagnosis of diabetes, we notified the patient's primary care provider of this diagnosis. One year after diagnosis, we reviewed these patients' medical records for traditional diabetes performance measures as well as blood pressure. Follow-up blood pressure was also ascertained from medical record review for all subjects with HbA(1c) > or =6.0% who did not have diabetes. We compared blood pressure changes between patients with and without diabetes.Among patients diagnosed with diabetes at screening, 34 of 53 (64%) had evidence of diet or medical treatment for their diabetes, 42 of 53 (79%) had HbA(1c) measured within the year after diagnosis, 32 of 53 (60%) had cholesterol measured, 25 of 53 (47%) received foot examinations, 29 of 53 (55%) had eye examinations performed by an eye specialist, and 16 of 53 (30%) had any measure of urine protein. The mean blood pressure decline over the year after diagnosis for patients with diabetes was 2.3 mmHg; this decline was similar to that found for 183 patients in the study without diabetes (change in blood pressure, -3.6 mmHg). At baseline, 48% of patients with diabetes had blood pressure <140/90, compared with 40% of patients without diabetes; 1 year later, the same 48% of patients with diabetes had blood pressure <140/90, compared with 56% of patients without diabetes (P = 0.31 for comparing the change in percent in control between groups).Patients with diabetes diagnosed at screening achieve less tight blood pressure control than similar patients without diabetes. Primary care providers do not appear to manage diabetes diagnosed at screening as intensively as long-standing diabetes and do not improve the management of hypertension given the new diagnosis of diabetes.
The impact of taxane-based preoperative chemotherapy in gastroesophageal signet ring cell adenocarcinomas
Authors: Stefano Kim, Frederic Fiteni, Sophie Paget-Bailly, François Ghiringhelli, Zaher Lakkis, Marine Jary, Francine Fein, Franck Bonnetain, Christophe Mariette, Christophe Borg
Journal: Journal of Hematology & Oncology (2015)

The benefit of preoperative chemotherapy in resectable gastroesophageal adenocarcinomas was not observed in signet ring cell subtype. However, the potential interest of taxane-based preoperative chemotherapy on this subtype is still an unresolved issue. Nineteen patients with localized signet ring cell adenocarcinomas received taxane-based regimens, and 17 patients underwent surgery. Complete resection was achieved in 80 %, and median overall survival was 40.8 months (95 % confidence interval (CI), 20.2-not reached). Even though one patient achieved a complete pathological response, seven patients had an upstaging of their tumors at surgery. The potential benefits of taxane-based chemotherapy seem to be limited to a reduced number of patients.
Plasma TIMP-1 levels and treatment outcome in patients treated with XELOX for metastatic colorectal cancer
Authors: C. Frederiksen, C. Qvortrup, I.J. Christensen, B. Glimelius, Å. Berglund, B.V. Jensen, S.E. Nielsen, N. Keldsen, H.J. Nielsen, N. Brünner, P. Pfeiffer
Journal: Annals of Oncology (2010)
S31 Characterisation of cell adhesion molecule-1 in lung mast cells
Authors: E. P. Moiseeva, M. Leyland, P. Bradding
Journal: Thorax (2010)

<h3>Introduction and Objectives</h3> Cell adhesion molecule 1 (CADM1) is implicated in several diseases and a prognostic factor for lung cancer. In human lung mast cells (HLMC) it contributes to cell-cell adhesion and proliferation. Functional CADM1 isoforms arise from alternative splicing between exons 7 and 11. Exon 9 may be functionally important because it encodes a specific cleavage site for TNF-alpha-cutting enzyme, TACE, in the longest SP1 and SP6 isoforms. Our aim was to characterise the isoforms of CADM1 expressed in HLMC. <h3>Methods</h3> CADM1 expression in isolated HLMC and human mast cell lines (HMC-1 and LAD2), was investigated using RT-PCR, cloning, and transfection. <h3>Results</h3> Multiple highly glycosylated CADM1 isoforms were found in HLMCs and cell lines. The SP4 isoform containing exon 8 represented ∼80% of clones in both HLMCs and ‘differentiated’ LAD2 cells, and ∼96% in non-differentiated HMC-1 cells. The SP1 isoform with exons 8+9 represented ≤20% of clones in HLMCs and LAD2 cells. A novel SP6 isoform with exons 8+9+10 was found only in HLMCs (&lt;5% of clones). More sensitive PCR analysis detected all these isoforms and an additional isoform SP3, lacking exons 8–10, in HLMCs and in cell lines. In contrast to these functional isoforms, non-functional isoforms were also found with two cryptic exons between exons 1 and 2, which cause a translational frame shift and premature termination of the protein. The cryptic exon B is located within the hot spot for SNPs. When the isoforms SP4, SP1 and SP6 were expressed in the HMC-1 cell line and the epithelial cell line HEK293 as fusion CADM1-GFP proteins, they were found at the cell periphery as well as in the cytoplasm. They were concentrated in cell boundaries in clumps of HMC1 cells. <h3>Conclusions</h3> Multiple and novel CADM1 isoforms are found in HLMCs. The longest SP1 and SP6 isoforms might be involved in the negative regulation of HLMC adhesion following secretion of TACE after activation. Some cryptic exons are likely to be a result of specific SNPs, creating new branching points for splicing. Non-functional cryptic CADM1 isoforms may reduce mature protein expression and affect the function of CADM1 expressing cells.
The Impact of the Diabetes Control and Complications Trial and Humalog Insulin on Glycohemoglobin Levels and Severe Hypoglycemia in Type 1 Diabetes
Authors: H. Peter Chase, Tai Lockspeiser, Ben Peery, Mark Shepherd, Todd MacKenzie, James Anderson, Satish K. Garg
Journal: Diabetes Care (2001)

OBJECTIVE—This study was performed to determine the effects of the Diabetes Control and Complications Trial (DCCT) report in 1993 and the introduction of Lispro (Humalog) insulin in 1996 on glycemic control and on the number of severe hypoglycemic episodes in type 1 diabetic patients of various ages. RESEARCH DESIGN AND METHODS—Diabetes care parameters and HbA1c data from 884 subjects with type 1 diabetes were entered into our database at the time of clinic visits from 1993 through 1998. In addition, a questionnaire was sent to all patients to validate the number of insulin injections per day, the incidence of severe hypoglycemic episodes (as defined by the DCCT), and the use of Humalog insulin. Data were divided into four age-groups: &amp;lt;5, 5–12, 13–18, and &amp;gt;18 years of age. RESULTS—Longitudinal HbA1c levels declined significantly after the DCCT report in 1993–1996 (P &amp;lt; 0.001), but the number of severe hypoglycemic events increased (P &amp;lt; 0.001). A second decline in HbA1c levels was observed after the introduction of Humalog insulin in 1996 (P &amp;lt; 0.001). However, severe hypoglycemic episodes did not change (P = 0.26). CONCLUSIONS—Administration of Humalog resulted in an additional reduction in HbA1c levels beyond the reduction in HbA1c values after the DCCT report. In contrast to the increase in severe hypoglycemic events after the DCCT results, the number of severe hypoglycemic episodes did not increase after the introduction of Humalog, despite a further decrease in HbA1c values.
Systemic tryptophan and kynurenine catabolite levels relate to severity of rhinovirus-induced asthma exacerbation: a prospective study with a parallel-group design
Authors: Koenraad F van der Sluijs, Marianne A van de Pol, Wim Kulik, Annemiek Dijkhuis, Barbara S Smids, Hetty W van Eijk, Jos A Karlas, Richard Molenkamp, Katja C Wolthers, Sebastian L Johnston, Jaring S van der Zee, Peter J Sterk, René Lutter
Journal: Thorax (2013)

<h3>Background</h3> Patients with allergic asthma have exacerbations which are frequently caused by rhinovirus infection. The antiviral tryptophan-catabolising enzyme indoleamine 2,3-dioxygenase (IDO) is induced by interferon-γ and suppressed by Th2 mediators interleukin (IL)-4 and IL-13. We hypothesised that local IDO activity after viral airway infection is lower in patients with allergic asthma than in healthy controls. <h3>Objective</h3> To determine whether IDO activity differs between patients with allergic asthma and healthy individuals before and after rhinovirus infection. <h3>Methods</h3> Healthy individuals and patients with allergic asthma were experimentally infected with low-dose (10 TCID<sub>50</sub>) rhinovirus 16. Blood, bronchoalveolar lavage fluid and exhaled breath condensate (for mass spectrometry by UPLC-MS/MS) were obtained before and after rhinovirus challenge. <h3>Results</h3> IDO activity was not induced by rhinovirus infection in either group, despite increases in cold scores. However, baseline pulmonary IDO activity was lower in patients with allergic asthma than in healthy individuals. In contrast, systemic tryptophan and its catabolites were markedly higher in patients with allergic asthma. Moreover, systemic quinolinic acid and tryptophan were associated with eosinophil cationic protein (r=0.43 and r=0.78, respectively) and eosinophils (r=0.38 and r=0.58, respectively) in bronchoalveolar lavage fluid and peak asthma symptom scores after rhinovirus challenge (r=0.53 and r=0.64, respectively). <h3>Conclusions</h3> Rhinovirus infection by itself induces no IDO activity, but the reduced pulmonary IDO activity in patients with allergic asthma at baseline may underlie a reduced control of viral infections. Notably, the enhanced systemic catabolism of tryptophan in patients with allergic asthma was strongly related to the outcome of rhinovirus challenge in asthma and may serve as a prognostic factor.
New Magnetic Resonance Imaging-Based Method for Defining the Extent of Left Atrial Wall Injury After the Ablation of Atrial Fibrillation
Authors: Christopher J. McGann, Eugene G. Kholmovski, Robert S. Oakes, Joshua J.E. Blauer, Marcos Daccarett, Nathan Segerson, Kelly J. Airey, Nazem Akoum, Eric Fish, Troy J. Badger, Edward V.R. DiBella, Dennis Parker, Rob S. MacLeod, Nassir F. Marrouche
Journal: Journal of the American College of Cardiology (2008)
Immigrants and Health Care
Authors: Caswell A. Evans Jr.
Journal: Annals of Internal Medicine (1995)

Letters15 September 1995Immigrants and Health CareCaswell A. Evans Jr., DDS, MPHCaswell A. Evans Jr., DDS, MPHPublic Health Programs and Services, Los Angeles, CA 90012Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-123-6-199509150-00035 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:I appreciate the validation and additional thoughts my article provoked. We are only beginning to see the possible ramifications of Proposition 187.One interesting and unforeseen outcome to the ballot measure is the record number of persons applying for citizenship. According to the Los Angeles Times, “citizenship applications … are up 500% from just a year ago—triggered in part by an inflamed political climate after the passage of Proposition 187” [1]. The intent of Proposition 187 was to discourage people from entering this country illegally. It has had the opposite effect; ever increasing numbers of persons could soon ...References1. McDonnell PJ. Applications for citizenship soar in L.A. Los Angeles Times. 10 April 1995. Google Scholar Author, Article, and Disclosure InformationAffiliations: Public Health Programs and Services, Los Angeles, CA 90012 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 September 1995Volume 123, Issue 6Page: 476KeywordsFallsHealth careMedical servicesPrevention, policy, and public health Issue Published: 15 September 1995 Copyright & PermissionsCopyright © 1995 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Connective Tissue Growth Factor and Its Role in Lung Adenocarcinoma Invasion and Metastasis
Authors: Cheng-Chi Chang, Jin-Yuan Shih, Yung-Ming Jeng, Jen-Liang Su, Been-Zen Lin, Szu-Ta Chen, Yat-Pang Chau, Pan-Chyr Yang, Min-Liang Kuo
Journal: JNCI Journal of the National Cancer Institute (2004)

Tumor invasion and metastasis cause most deaths in cancer patients. Connective tissue growth factor (CTGF), a secreted protein that binds to integrins, modulates the invasive behavior of certain human cancer cells, but few mechanistic details are known. We investigated the roles of CTGF and collapsin response mediator protein 1 (CRMP-1) in metastasis and invasion of human lung adenocarcinoma.We compared vector control-transfected cells with corresponding CTGF gene-transfected cells. Invasive activity was measured with a modified Boyden chamber assay, and metastatic activity was measured in an animal model. We used CTGF deletion mutants, CTGF and CRMP-1 antisense oligonucleotides, and anti-integrin and anti-CRMP-1 antibodies to investigate the functional relationship between CTGF and CRMP-1. Expression of CTGF protein in 78 lung adenocarcinoma specimens was investigated immunohistochemically. All statistical tests were two-sided.Invasive (both P<.001) and metastatic (P<.001 and P=.003, respectively) activities were lower in cells that overexpress CTGF than in vector control cells. Expression of CRMP-1 was higher in CTGF-transfected clones than in vector control cells, and its level decreased after cells were treated with anti-integrin alpha(v)beta3 and alpha(v)beta5 antibodies. Reduced levels of CRMP-1 protein after the transfection of CRMP-1-specific antisense oligonucleotides, but not sense oligonucleotides, increased the invasiveness of CTGF-transfected cells (mean numbers of invasive CTGF-transfected cells treated with 20 microM CRMP-1-specific sense and antisense oligonucleotides were 327 and 516 cells, respectively [difference = 189 cells, 95% confidence interval [CI] = 156 to 221 cells; P<.001]). The CT module of CTGF was the region primarily responsible for the increased expression of CRMP-1 and the inhibition of invasion (mean numbers of invasive cells expressing full-length CTGF and CT module-deleted mutant were 148 and 385 cells, respectively [difference = 237 cells, 95% CI = 208 to 266 cells; P<.001]). Reduced expression of CTGF in lung cancer specimens was statistically significantly associated with the risk of more advanced-stage disease (stages III and IV versus stages I and II; P=.001), lymph node metastasis (P =.014), and shorter survival (median survival with high levels of CTGF = 66.7 months and median survival for low levels = 18.2 months; difference = 48.5 months, 95% CI = 33.5 to 63.5 months; P =.02).CTGF inhibits metastasis and invasion of human lung adenocarcinoma by a CRMP-1-dependent mechanism.
US women's attitudes to false positive mammography results and detection of ductal carcinoma in situ: cross sectional survey
Authors: L. M Schwartz
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objective:</b> To determine women9s attitudes to and knowledge of both false positive mammography results and the detection of ductal carcinoma in situ after screening mammograph. <b>Design:</b> Cross sectional survey. <b>Setting:</b> United States. <b>Participants:</b> 479 women aged 18–97 years who did not report a history of breast cancer. <b>Main outcome measures:</b> Attitudes to and knowledge of false positive results and the detection of ductal carcinoma in situ after screening mammography. <b>Results:</b> Women were aware that false positive results do occur. Their median estimate of the false positive rate for 10 years of annual screening was 20% (25th percentile estimate, 10%; 75th percentile estimate, 45%). The women were highly tolerant of false positives: 63% thought that 500 or more false positives per life saved was reasonable and 37% would tolerate 10 000 or more. Women who had had a false positive result (n=76) expressed the same high tolerance: 39% would tolerate 10 000 or more false positives. 62% of women did not want to take false positive results into account when deciding about screening. Only 8% of women thought that mammography could harm a woman without breast cancer, and 94% doubted the possibility of non-progressive breast cancers. Few had heard about ductal carcinoma in situ, a cancer that may not progress, but when informed, 60% of women wanted to take into account the possibility of it being detected when deciding about screening. <b>Conclusions:</b> Women are aware of false positives and seem to view them as an acceptable consequence of screening mammography. In contrast, most women are unaware that screening can detect cancers that may never progress but feel that such information would be relevant. Education should perhaps focus less on false positives and more on the less familiar outcome of detection of ductal carcinoma in situ.