tbuckley/cabot-search huggingface dataset:
Abstract 126: Pregnancy Hormones Induce An Increase Of Capillary Density In The Mouse Heart
Authors: Michael Hesse, Daniel Korzus, Kristina Thaben, Bernd K Fleischmann
Journal: Circulation Research (2014)

During pregnancy the maternal organism undergoes a variety of adaptive physiological changes. The cardiovascular system is strongly affected and its response is characterized by cardiac hypertrophy. The molecular mechanisms underlying these adaptations are still poorly understood. The recent postulation of resident organotypic stem cells in the cardiovascular system prompted us to explore the potential involvement of these cells and the related signaling cascades involved in this adaptation process in the heart. We have analyzed cell proliferation using immunostainings in mouse hearts at different stages during pregnancy. The average percentage of proliferating cells in cardiac sections increased from virgin controls to gestational day 3 (GD3), peaked at GD14, and immediately stopped after delivery. Co-staining revealed that the majority of proliferating cells were fibroblasts and endothelial cells (ECs). The lack of cardiomyocyte proliferation was corroborated using BrdU pulse chase experiments analyzed in single cells upon Langendorff perfusion. The proliferation of fibroblasts and ECs reflects angiogenesis, which was underscored by an increase of capillary density, and extracellular matrix remodeling known to occur during pregnancy induced hypertrophy. To mimic the action of pregnancy hormones we implanted pellets with constant release of hormone for 21 days subcutaneously in ovariectomized mice. Capillary density was significantly increased in mice receiving progesterone-pellets alone or in combination with estrogen-pellets without induction of hypertrophy. Thus, increase of capillary density is directly induced by pregnancy hormones. Assessment of differentially expressed genes after hormone treatment revealed induction of angiogenetic factors and their receptors. We are currently investigating the mechanisms underlying the pregnancy hormone-induced proliferation in cardiac ECs and fibroblasts.
AIP1 Expression in Tumor Niche Suppresses Tumor Progression and Metastasis
Authors: Weidong Ji, Yonghao Li, Yun He, Mingzhu Yin, Huanjiao Jenny Zhou, Titus J. Boggon, Haifeng Zhang, Wang Min
Journal: Cancer Research (2015)

Studies from tumor cells suggest that tumor-suppressor AIP1 inhibits epithelial-mesenchymal transition (EMT). However, the role of AIP1 in the tumor microenvironment has not been examined. We show that a global or vascular endothelial cell (EC)-specific deletion of the AIP1 gene in mice augments tumor growth and metastasis in melanoma and breast cancer models. AIP1-deficient vascular environment not only enhances tumor neovascularization and increases premetastatic niche formation, but also secretes tumor EMT-promoting factors. These effects from AIP1 loss are associated with increased VEGFR2 signaling in the vascular EC and could be abrogated by systemic administration of VEGFR2 kinase inhibitors. Mechanistically, AIP1 blocks VEGFR2-dependent signaling by directly binding to the phosphotyrosine residues within the activation loop of VEGFR2. Our data reveal that AIP1, by inhibiting VEGFR2-dependent signaling in tumor niche, suppresses tumor EMT switch, tumor angiogenesis, and tumor premetastatic niche formation to limit tumor growth and metastasis.
Delayed complication of Port-A-Cath: perforation of the superior vena cava.
Authors: N Kulvatunyou, J Rucinski, M Schein
Journal: Journal of Clinical Oncology (1997)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1997.15.2.865 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 9053519 Delayed complication of Port-A-Cath: perforation of the superior vena cava. N KulvatunyouxN KulvatunyouSearch for articles by this author , J RucinskixJ RucinskiSearch for articles by this author , M ScheinxM ScheinSearch for articles by this author https://doi.org/10.1200/JCO.1997.15.2.865 PDF "Delayed complication of Port-A-Cath: perforation of the superior vena cava.." Journal of Clinical Oncology, 15(2), p. 865© 1997 by American Society of Clinical Oncology
Activation of thymidine salvage pathway measured with FLT PET, as a potential indicator of response to 5FU in colorectal cancer
Authors: F. Pakzad, M. Loizidou, P. J. Ell, I. Taylor
Journal: Journal of Clinical Oncology (2005)

3572 Background: The commonly used positron emission tomography (PET) tracer is [18F]-Fluoro-2-deoxy-D-glucose (FDG). [18F]-3-fluoro-3-deoxy-L-thymidine (FLT) is a novel tracer, with cellular uptake mechanisms linked to the pyrimidine salvage enzyme, thymidine kinase-1 (TK-1). The colorectal cancer chemotherapeutic agent, 5-Fluorouracil (5FU), inhibits de novo pyrimidine synthesis. Therefore, we investigated changes in FLT and FDG uptake after 5FU treatment, to determine their potential in detecting early evidence of response to 5FU in vitro. Methods: Human colorectal cancer cell cultures (SW480, SW620) were treated with 5FU (50μg/ml, 2h). Cells were washed, incubated with FLT or [18F]-Fluoro-2-deoxy-D-glucose (FDG) for comparison (100kBq, 90 min). Cells were subsequently harvested and uptake was determined using a gamma counter. TK-1 expression was detected by Western blotting. Changes in S-phase fraction (SPF) of treated cell were examined by flow cytometry. Results: Cytotoxic dose of 5FU chosen showed minimal cell killing immediately after treatment (0–10% (p=NS). However, 50% cell killing was achieved at 24 hours. A mean 2.96 fold increase (2.82 ± 0.2, SW480; 3.10± 0.3 SW620) in total FLT uptake (per 10 5 cells) was observed in treated cells vs controls (p<0.01). However, no difference was observed in FDG uptake. The increase in FLT uptake post 5FU treatment correlated with increased TK-1 expression in both cell lines. No significant change in the SPF of 5FU treated cells was observed. Conclusions: An early biological response to 5FU treatment was measured with FLT and not FDG. This effect correlated with an increased expression of thymidine salvage enzyme TK-1, before changes in the cell cycle were observed. FLT PET may potentially be used as an indicator of response to 5FU based chemotherapeutic agents before changes in morphology become apparent. No significant financial relationships to disclose.
Markers of sudden cardiac arrest in patients with severe respiratory infections
Authors: Ekaterina Epova, Sergey Lukyanov, Vladimir Gorbunov, Alexandra Kochneva
Journal: European Respiratory Journal (2014)

Introduction . The sudden cardiac arrest (SCA) in patients hospitalized due to severe respiratory infection is a stubborn problem. Often it occurs suddenly and outside the intensive care unit (ICU) [Dr. Carr et al. In-Hospital Cardiac Arrest Among Patients With Coexisting Pneumonia: A Report From The American Heart Association, Abstract of American Thoracic Society9s 2011 International Conference in Denver]. However predictors of SCA are still unclear.  Aims and objectives.  The aim of the study was the analysis of SCA frequency in severe respiratory infection and studying of factors associated with it.  Methods.  55 pts with severe respiratory infections in ICU and respiratory department were examined. Respiratory infections (severe pneumonias) were verified on the basis of existence of lung infiltrate according on a chest X-ray or CT-scans. All of the patients recieved additional oxygen or respiratory support, antibiotics and fluid resuscitation. Multifactorial regression analysis and the relative risk indicator were calculated.  Results.  Despite a carried-out intensive care 22 pts (40%) died. The sudden cardiac arrest occurred in 8 pts (36,3%), not because of septic shock or multiorgan dysfunction. All of patients at the time of SCA were in full consciousness, and the probable cause of SCA was the cardiac arrhythmia. The multiple regression analysis showed that the main predictors of SCA were the extended QT interval (RR=2,2 [1,3; 3;8]) and the low level of SpO2 (l90%) (RR=3,4 [2,7; 7;33]).  Conclusion.  The sudden cardiac arrest is a frequent complication of severe respiratory infections which major harbingers are the extended QT interval and the low level of SpO2. This problem demands further studying.
Antibody to Epiglycanin and Radioimmunoassay to Detect Epiglycanin-Related Glycoproteins in Body Fluids of Cancer Patients&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: J F Codington, V P Bhavanandan, K J Bloch, N Nikrui, J V Ellard, P S Wang, R W Jeanloz
Journal: JNCI Journal of the National Cancer Institute (1984)

By means of a radioimmunoassay, which utilized [125I]-epiglycanin and anti-epiglycanin antiserum induced in rabbits by injections of viable TA3-Ha ascites cells with Freund's complete adjuvant, picogram quantities of epiglycanin could be detected. Anti-epiglycanin antiserum was similarly produced in allogeneic mice. Unlabeled epiglycanin lost the capacity to compete with [125I]epiglycanin in the radioimmunoassay as a result of periodate oxidation or incubation with endo-alpha-N-acetyl-D-galactosaminidase (Diplococcus pneumoniae), an enzyme found to cleave only the disaccharide beta-D-galactopyranosyl-(1----3)-2-acetamido-2-deoxy-D-galactose chain from serine or threonine residues in epiglycanin. Glycosylhydrolases known to cleave alpha-D-mannose, beta-D-galactose (1,4-linked), beta-N-acetyl-D-glucosamine, and alpha-N-acetyl-D-galactosamine did not reduce the activity of epiglycanin. Neuraminidase enhanced the activity twofold to fivefold. The finding that little or no activity was demonstrated by the disaccharide, the reduced disaccharide, or other glycoproteins containing the same disaccharide chain suggested that the antigenic determinant probably involved the disaccharide and a unique amino acid sequence at the site of its attachment. By means of the radioimmunoassay epiglycanin cross-reactive antigens were detected in the peritoneal or pleural fluid and in the sera of patients with metastatic cancer. Lower concentrations of epiglycanin-like antigen(s) were found in the peritoneal fluid of patients with hepatitis or liver cirrhosis but not in normal serum.
The particularities of pulmonary tuberculosis (TB)-diabetus mellitus (DM) syntropy in a community with high prevalence for TB
Authors: Ghiulten Apti, Anamaria Trailescu
Journal: European Respiratory Journal (2011)

It is well known that patients with DM had a greater risk for TB. Our city is known with one of the highest prevalence of TB in our country. Aim to investigate the features of TB-DM syntropy;

We made a case control epidemiologic study - on 292 patients hospitalized between 2005-2009; we enrolled 146 patients diagnosed with new case-TB (group 1) and 146 patients with TB and DM (group 2);data were collected by reviewing the medical records of hospitalized patients.

Results: In group 2 DM was diagnosed after TB in 24%;TB occurred after an average period of 5,5 years in those with previous DM;DM had type 1 in 34% and type 2 insulin necessitant 50,1%; in both groups predominated insidious onset; hemoptysia was more frequent in TB lot and fever and malaise in DM-TB; in 6% onset was with diabetic coma. Radiological pattern:in group 2 predominated bilateral infiltrates (extensive form) and atypical localization (lower lobs);pleurisy and cavitation were frequent in group 1; bacteriological exam 74% smear positive in group 2 and 71% in group 1;the rate of negativity under treatment was slower in lot 2: 37% still positive after 2 months, and 7% after 3 months; complications under treatment occurred more frequent in group 2 (hepatitis and hematologic changes);costs with medication and hospitalization (average: 78±16days) were greater in group 2 (about three fold); early relapses occurred only in 3,9% in group 2 and 9,2% in group 1 (p=0,001).

Conclusions: DM represent a risk for TB; Time between onset of DM and TB was shorter than in literature. in DM patients disease is more extensive with slower healing and high percent of complication during treatment than those without DM.
High D-dimer levels after stopping anticoagulants in pulmonary embolism with sleep apnoea
Authors: Angela García Suquia, Alberto Alonso-Fernández, Mónica de la Peña, David Romero, Javier Piérola, Miguel Carrera, Antonia Barceló, Joan B. Soriano, Meritxell Arque, Carmen Fernández-Capitán, Alicia Lorenzo, Francisco García-Río
Journal: European Respiratory Journal (2015)

Obstructive sleep apnoea is a risk factor for pulmonary embolism. Elevated D-dimer levels and other biomarkers are associated with recurrent pulmonary embolism. The objectives were to compare the frequency of elevated D-dimer levels (&gt;500 ng·mL −1 ) and further coagulation biomarkers after oral anticoagulation withdrawal in pulmonary embolism patients, with and without obstructive sleep apnoea, including two control groups without pulmonary embolism. We performed home respiratory polygraphy. We also measured basic biochemical profile and haemogram, and coagulation biomarkers (D-dimer, prothrombin fragment 1+2, thrombin-antithrombin complex, plasminogen activator inhibitor 1, and soluble P-selectin). 64 (74.4%) of the pulmonary embolism cases and 41 (46.11%) of the controls without pulmonary embolism had obstructive sleep apnoea. Plasmatic D-dimer was higher in PE patients with OSA than in those without obstructive sleep apnoea. D-dimer levels were significantly correlated with apnoea–hypopnoea index, and nocturnal hypoxia. There were more patients with high D-dimer after stopping anticoagulants in those with pulmonary embolism and obstructive sleep apnoea compared with PE without obstructive sleep apnoea (35.4% versus 19.0%, p=0.003). Apnoea–hypopnoea index was independently associated with high D-dimer. Pulmonary embolism patients with obstructive sleep apnoea had higher rates of elevated D-dimer levels after anticoagulation discontinuation for pulmonary embolism than in patients without obstructive sleep apnoea and, therefore, higher procoagulant state that might increase the risk of pulmonary embolism recurrence.
Relevance of measurement of serum periostin for diagnosing bronchial asthma and estimating its lung function abnormalities
Authors: Kenya Kohyama, Kenji Izuhara, Akemi Kohyama, Kentaro Nakano, Ryosuke Souma, Kiyokazu Kikuchi, Hideyuki Satoh, Takenori Okada, Naoto Fueki, Shoicihiro Ohta, Junya Ono, Yoshinori Azuma, Hironori Sagara
Journal: European Respiratory Journal (2012)

Bronchial asthma is diagnosed by combination of presence of characteristic symptoms and measurement of reversibility of lung function abnormalities. Non-invasive markers such as levels of exhaled nitric oxide (FeNO) and sputum eosinophilia have potential usefulness for diagnosis of bronchial asthma and determination of optimal treatment; however, these biomarkers contain several problems in specificity in diseases. Periostin, an extracellular matrix protein downstream of IL-4/IL-13 signals, has emerged as a novel biomarker for bronchial asthma. Particularly, it has been recently shown that efficacy of anti-IL-13 antibody can be predicted using serum periostin levels in steroid-resistant asthma patients. However, it still remains undetermined how measurement of serum periostin level is relevant for diagnosing bronchial asthma. The study group comprised 37 patients with asthma and 30 healthy subjects. In both groups, serum concentrations of SCCA1, SCCA2, periostin (SS18A SS17B) were measured. In asthmatic patients, serum IgE concentrations, eosinophil counts, and exhaled NO levels were also measured. Serum concentrations of periostin (SS18A SS17B) was significantly higher in the asthmatic patients than in the control subjects. Serum concentrations of both types of periostin strongly correlated with eosinophil counts and exhaled NO levels. In contrast, serum SCCA concentrations did not differ between the control subjects and asthmatic patients or significantly correlate with any variable studied.Our results suggested that serum periostin concentrations may be a significant diagnostic marker of bronchial asthma that correlates with eosinophil counts.
Aryl hydrocarbon receptor-microRNA-212/132 axis in human breast cancer suppresses metastasis by targeting SOX4
Authors: Hamza Hanieh
Journal: Molecular Cancer (2015)

MicroRNAs (miRNAs) are a class of short non-coding RNAs that pave a new avenue for understanding immune responses and cancer progression. Although the miRNAs are involved in breast cancer development, their axis with the transcription factors that show therapeutic potential in breast cancer is largely unknown. Previous studies showed anti-metastatic roles of agonist-activated aryl hydrocarbon receptor (Ahr) in various breast cancer cell lines. Recently, we demonstrated that agonist-activated Ahr induced a highly conserved miRNA cluster, named miR-212/132, in murine cellular immune compartment. Therefore, current study was performed to examine if this miRNA cluster mediates the anti-metastatic properties of Ahr agonists.The expression of miR-212/132 cluster and coding genes were examined by real-time PCR, and the protein levels were detected by western blot. The 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 3,3'-diindolylmethane (DIM) were used to activate Ahr in MDA-MB-231 and T47D breast cancer cells. Chromatin immunoprecipitation (ChIP) assay was used to identify the binding site(s) for Ahr on miR-212/132 promoter. For prediction of potentially target gene of the miRNA cluster, bioinformatics analysis was carried out, and to test targeting, luciferase activity was quantified. Besides, biological effects of Ahr-miR-212/132 axis were examined in vitro by cell migration, expansion and invasion, and examined in vivo by orthotopic model of spontaneous metastasis.The miR-212/132 cluster was transcriptionally activated in MDA-MB-231 and T47D cells by TCDD and DIM, and this activation was regulated by Ahr. A reciprocal correlation was identified between Ahr agonists-induced miR-212/132 and the pro-metastatic SRY-related HMG-box4 (SOX4), and a new specific binding sites for miR-212/132 were identified on the untranslated region (3'UTR) of SOX4. Interestingly, miR-212/132 over-expression showed direct anti-migration, anti-expansion and anti-invasion properties, and an inhibition of the miRNA cluster mitigated the anti-invasive properties of TCDD and DIM. Further in vivo studies demonstrated that the Ahr-miR-212/132-SOX4 module was induced by Ahr activation.Taken together, the findings provide the first evidences of the synergistic anti-metastatic properties of miR-212/132 cluster through suppression of SOX4. Also, current study suggest a new miRNA-based mechanism elucidating the anti-metastatic properties of Ahr agonists, suggesting possibility of using miR-212/132 to control metastasis in breast cancer patients.
Varicella‐zoster virus antigen expression of eccrine gland and duct epithelium in herpes zoster lesions
Authors: C. Horie, Y. Mizukawa, Y. Yamazaki, T. Shiohara
Journal: British Journal of Dermatology (2011)

Background It is well known that varicella-zoster virus (VZV) exhibits tropism for the epidermis and follicular epithelium, while little attention has been paid to eccrine gland and duct involvement by VZV. The presence of herpetic syringitis in immunocompromised hosts suggested the possibility of eccrine gland and duct involvement by VZV. Objectives To determine whether VZV antigens could be detected in eccrine gland or duct epithelium of herpes zoster (HZ) lesions obtained at various intervals after the onset of a rash, and whether this expression could also be detected in eccrine units from other inflammatory disease lesions suggestive of VZV infection. Methods We investigated immunohistochemically in vivo localization of VZV glycoprotein E (gE) antigen in HZ lesions and control inflammatory disease lesions, using the murine monoclonal antibody directed against the VZV gE. Results VZV gE was differentially detected in the epidermis, follicular and eccrine epithelium, and dermal infiltrating cells in HZ lesions obtained at various intervals after onset. The VZV gE was most persistently detected in eccrine units, regardless of the age of individual HZ lesions, compared with keratinocytes and follicular epithelium. The gE expression was also observed in other inflammatory disease lesions suggestive of VZV infection. Conclusions Immunohistochemical detection of VZV gE in eccrine epithelium can be a subtle clue to the diagnosis of HZ which displays most unusual manifestations, and VZV-related disorders.
Mechanisms of orthostatic proteinuria
Authors: P Devarajan
Journal: Journal of the American Society of Nephrology (1993)

Orthostatic proteinuria accounts for 60% of all children and 75% of adolescents with proteinuria. Despite its frequent occurrence, the underlying pathophysiologic mechanisms remain unclear. The following three possibilities have been reviewed: (1) a normal variant; (2) a glomerular abnormality; (3) a hemodynamic abnormality. On the basis of the experience with an individual who had orthostatic proteinuria and who was a donor of a living-related kidney transplant, novel insights and a potentially unifying hypothesis for the pathogenesis of this condition are presented. It is suggested that individuals with orthostatic proteinuria may be predisposed by a subtle glomerular abnormality. However, a precipitating factor, in the form of an exaggerated response to the upright position, appears to be essential to unmask the condition.
Metabolic studies of rat renal tubule cells loaded with cystine
Authors: J W Foreman, L L Benson, M Wellons, E D Avner, W Sweeney, I Nissim, I Nissim
Journal: Journal of the American Society of Nephrology (1995)

The cause of Fanconi syndrome in cystinosis is enigmatic. It has previously been shown that renal tubules could be loaded with cystine by incubating them with cystine dimethylester (CDE), mimicking the biochemical hallmark of cystinosis. Such tubules have impaired transport, decreased whole-cell O2 consumption, and substrate utilization. In this study, the metabolic disturbances in cystine-loaded renal tubule cells were further characterized. Isolated rat renal tubules were loaded with cystine by incubating them with 2 mM CDE for 10 min. This had no significant effect on total ATPase, Na(+)-K(+)-ATPase, or the ouabain-insensitive ATPase activity of renal tissue homogenates from these cystine-loaded tubules. Intracellular K was significantly lower in the cystine-loaded tubules (37 +/- 2 versus 47 +/- 3 nEq/mg; P < 0.008). Intracellular ATP was reduced by 39% in the cystine-loaded tubules (23.7 +/- 2.4 versus 38.1 +/- 3.3 nmol/mg of protein; P < 0.0025). CDE (2 mM) reduced isolated mitochondrial O2 consumption with glutamate as the substrate by 66% (4.7 +/- 0.7 versus 13.9 +/- 0.8 nm/min per mg of protein, P < 0.001) but had no effect on mitochondrial O2 consumption with succinate as the substrate. It was speculated that the impaired transport from cystine loading with CDE is secondary to a decrease in energy generation.