tbuckley/cabot-search huggingface dataset:
Extensive domain shuffling in transcription regulators of DNA viruses and implications for the origin of fungal APSES transcription factors
Authors: Lakshminarayan M Iyer, Eugene V Koonin, L Aravind
Journal: Genome biology (2002)

Viral DNA-binding proteins have served as good models to study the biochemistry of transcription regulation and chromatin dynamics. Computational analysis of viral DNA-binding regulatory proteins and identification of their previously undetected homologs encoded by cellular genomes might lead to a better understanding of their function and evolution in both viral and cellular systems. The phyletic range and the conserved DNA-binding domains of the viral regulatory proteins of the poxvirus D6R/N1R and baculoviral Bro protein families have not been previously defined. Using computational analysis, we show that the amino-terminal module of the D6R/N1R proteins defines a novel, conserved DNA-binding domain (the KilA-N domain) that is found in a wide range of proteins of large bacterial and eukaryotic DNA viruses. The KilA-N domain is suggested to be homologous to the fungal DNA-binding APSES domain. We provide evidence for the KilA-N and APSES domains sharing a common fold with the nucleic acid-binding modules of the LAGLIDADG nucleases and the amino-terminal domains of the tRNA endonuclease. The amino-terminal module of the Bro proteins is another, distinct DNA-binding domain (the Bro-N domain) that is present in proteins whose domain architectures parallel those of the KilA-N domain-containing proteins. A detailed analysis of the KilA-N and Bro-N domains and the associated domains points to extensive domain shuffling and lineage-specific gene family expansion within DNA virus genomes. We define a large class of novel viral DNA-binding proteins and their cellular homologs and identify their domain architectures. On the basis of phyletic pattern analysis we present evidence for a probable viral origin of the fungus-specific cell-cycle regulatory transcription factors containing the APSES DNA-binding domain. We also demonstrate the extensive role of lineage-specific gene expansion and domain shuffling, within a limited set of approximately 24 domains, in the generation of the diversity of virus-specific regulatory proteins.
In Vivo Gene Transfection With Hepatocyte Growth Factor via the Pulmonary Artery Induces Angiogenesis in the Rat Lung
Authors: Masamichi Ono, Yoshiki Sawa, Kunio Matsumoto, Toshikazu Nakamura, Yasufumi Kaneda, Hikaru Matsuda
Journal: Circulation (2002)

Background Recent studies have demonstrated that gene transfer with hepatocyte growth factor (HGF) induces angiogenesis for coronary and peripheral artery diseases. We investigated the ability of gene transfer with human HGF to induce angiogenesis in the rat lung. Methods and Results The left lung was selectively transfected with a cDNA encoding human HGF via the left pulmonary artery, using the HVJ-liposome method (H group); rats transfected with the same vector lacking the HGF gene served as controls (C group). HGF gene transfer significantly increased the capillary density in the left lung compared with the C group 7 days after transfection (15.0±1.3 versus 8.0±1.7 mm 2 , P &lt;0.01). The left to right average blood perfusion ratio detected by laser Doppler imaging increased significantly in the H group 14 days after transfection (1.12±0.09 versus 0.91±0.11, P &lt;0.01). A right pulmonary artery clamp test, in which only the left lung received all the pulmonary blood flow from the right ventricle, revealed that the increase in right ventricular pressure was significantly attenuated in the H group compared with the C group 7 days after transfection (8.6±3.5 versus 15.3±2.8 mm Hg, P &lt;0.01). Conclusions Trans-pulmonary arterial transfer of the human HGF gene into the left lung increased capillary density and blood perfusion, and decreased vascular resistance when blood flow increased. These results suggest therapeutic angiogenesis induced by HGF gene expression in the lung may be found suitable in treating subjects with decreased pulmonary vasculature or increased pulmonary vascular resistance.
Volatile organic compounds may provide a new and promising tool for diagnosing interstitial lung diseases
Authors: Agnes Boots, Roel Schins, Roger Godschalk, Catrin Albrecht, Jan Dallinga, Aalt Bast, Florence Schleich, Marjolein Drent, Frederik-Jan van Schooten
Journal: European Respiratory Journal (2012)

Diagnosing interstitial lung diseases (ILD) requires invasive techniques. A new, non-invasive diagnostic tool includes analyzing volatile organic compounds (VOCs) in exhaled air as they can be applied as biomarkers of e.g. oxidative stress and inflammation.  To i n vitro  mimic ILD-related damage, human epithelial cells were exposed to bleomycin and headspace air and supernatants were collected. The supernatants were used to analyze cytotoxicity and markers of oxidative stress and inflammation. The headspace air was analyzed using time of flight GC-MS after which a discriminating VOC profile was composed.  To  in vivo  identify VOC patterns specific for ILD patients, the breath of 50 ILD patients and 50 healthy controls was screened for distinctive VOCs.  The  in vitro  volatome consisted of >2000 compounds of which 5 VOCs correctly classified samples with 95% correctness using the original data set and 85% using cross-validated observations. Although chemical identification of these compounds is ongoing, preliminary data suggest that they are oxygen-containing poly-unsaturated hydrocarbons resulting from lipid peroxidation. Additionally, markers of oxidative stress and inflammation were elevated upon bleomycin treatment (P  The  in vivo  volatome consisted of >6000 compounds that are currently under analysis. Interestingly, preliminary data show that discrimination between patients and controls, as well as between various severity stages of ILD, is possible based on a limited VOC number.  VOC analysis appears to be very promising in detecting ILD-like changes  in vitro  and is currently investigated as a new tool for diagnosing ILD  in vivo .
Tamoxifen versus high-dose oral medroxyprogesterone acetate as initial endocrine therapy for patients with metastatic breast cancer: a Piedmont Oncology Association study.
Authors: H B Muss, L D Case, J N Atkins, J D Bearden, M R Cooper, J M Cruz, D V Jackson, M A O'Rourke, M D Pavy, B L Powell
Journal: Journal of Clinical Oncology (1994)

To determine in a prospective randomized trial whether high-dose orally administered medroxy-progesterone acetate (MPA) was superior to tamoxifen in patients with recurrent or metastatic breast cancer who had received no prior endocrine therapy in either the adjuvant or advanced setting.Patients initially received either tamoxifen 20 mg/d orally or MPA 1 g/d orally. At the time of disease progression, patients were crossed over to the other regimen. Eligibility required patients to be age > or = 18 years, performance status 0 to 3, and estrogen receptor (ER)- or progesterone receptor (PR)-positive or unknown.One hundred eighty-two eligible patients were entered and 166 were assessable for response. Complete plus partial response rates for tamoxifen and MPA were 17% and 34%, respectively (P = .01). Patients with bone metastases had a significantly higher partial response rate with MPA compared with tamoxifen (33% v 13%). Median time to treatment failure was 5.5 months for tamoxifen and 6.3 months for MPA (P = .48). The median survival duration was 24 months for tamoxifen and 33 months for MPA (P = .09). Multivariate analysis showed that treatment significantly influenced response rate, but not time to treatment failure or survival. After treatment failure following MPA, six of 42 patients (14%) treated with tamoxifen responded, compared with six of 49 (12%) treated with MPA following tamoxifen. Both agents were associated with minimal toxicity, but 35% of patients on MPA gained more than 20 lb as opposed to only 2% on tamoxifen.In this trial, initial treatment with MPA of endocrine-naive metastatic breast cancer patients was associated with a significantly higher response rate but not with improvement in time to treatment failure or survival, when compared with initial treatment with tamoxifen. Further randomized trials in patients with bone metastases are warranted to determine if high-dose progestin therapy is superior to tamoxifen in these patients.
Role of High-Fat Diet in Tumorigenesis in C57BL/1 Mice&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn4"&gt;4&lt;/xref&gt;
Authors: S M El-Khatib, E M Cora
Journal: JNCI Journal of the National Cancer Institute (1981)

To determine if high contents of polyunsaturated fatty acids and estrogen might induce tumor formation in certain tissues of animals and to determine if the contents of the different classes of lipids in susceptible tissues would be changed, mice from the inbred C57BL/1 strain were fed the following diets: 1) Purina Laboratory Chow only (diet 1), which served as control; 2) Purina Laboratory Chow supplemented with corn oil and oleic acid (diet II); and 3) Purina Laboratory Chow supplemented with corn oil and estrogen (diet III). Although C57BL/1 mice are generally resistant to tumor formation, the present study showed that 8% of the mice maintained on diet II developed histologically confirmed adenocarcinoma of the colon, which metastasized to the lung and muscle. No macroscopic tumors were seen in mice maintained on diet III; however, fatty livers were seen in mice from this group (litters 5/313, 5/310). Total lipid and cholesterol contents in 6- and 12-month-old experimental mice were significantly higher than those in controls but not in older animals. In the pituitary glands of the 18- and 21-month-old control mice, total cholesterol content seemed higher than that of the experimental mice. Only livers of 12-month-old experimental mice showed significantly lower phospholipid content than that of the controls. Only the triglyceride content of livers from 18-month-old experimental mice was significantly higher than that of the controls. Finally, the ratio of saturated to unsaturated free fatty acids in livers of experimental mice was significantly altered from that of the control mice.
Cost of Outpatient Blood Transfusion in Cancer Patients
Authors: Pierre-Yves Crémieux, Barbara Barrett, Kenneth Anderson, Mitchell B. Slavin
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To determine the cost of outpatient RBC transfusion from the provider’s perspective at a major urban, academic cancer center. PATIENTS AND METHODS: We retrospectively studied 517 cancer patients with hematologic or solid tumors who received blood during fiscal year 1995 to 1996. A process-flow diagram was developed, and cost and utilization data for 12 months were collected and analyzed. A structured interview process was used to identify all direct and indirect costs from within the inpatient unit, blood bank, and outpatient clinic. Average costs were computed for the entire sample and for specific subgroups. RESULTS: In 1998 dollars, the average cost per RBC unit was $469 for adults and $568 for pediatric cancer patients. Adults and children generally received two and one RBC units per transfusion, respectively. Therefore, the average cost of a two-unit transfusion was $938 for adults. Patients with hematologic tumors required more RBC units (7.1 RBC units per year) at a higher average cost ($512 per RBC unit) than patients with solid tumors (4.7 RBC units per year, $474 per RBC unit). Further variations across tumor types were observed. Overhead, direct material, and direct labor represented 46%, 19%, and 35% of total costs respectively. CONCLUSION: The cost of outpatient RBC transfusions in cancer patients is higher than previously reported, in part because overhead costs and fixed costs might have been underestimated in previous studies. Furthermore, age, tumor type, and geographic variations in the cost of fixed assets and labor have a substantial impact on the cost of blood. The results indicate that the cost-effectiveness of alternatives to transfusions in the management of cancer patients may have been underestimated in the existing literature.
Ovariectomy Alone or in Combination With Dexamethasone in Patients With Advanced Breast Cancer and High Levels of Testosterone Excretion
Authors: Renzo Grattarola
Journal: JNCI Journal of the National Cancer Institute (1976)

The urinary testosterone levels of 40 premenopausal and postmenopausal patients with advanced breast carcinoma were assayed before and after ovariectomies. Histologic examination of the ovaries of 25 patients whose hormone levels were above normal revealed interstitial cell hyperplasia. Two months after the operations, the amounts of testosterone excreted by the womaen decreased significantly. We considered this as indirect evidence that the ovaries contributed to androgen synthesis. However, 15 patients had normal hormone excretion values that did not change 2 months postoperatively. Testosterone levels for 6 of the women 5 months after surgery were higher than at the previous testing. We surmised that the increased gonadotropic activity that followed ovariectomy migh have stimulated adrenal androgen secretion. To elucidate this point, we gave injections of 15,000 IU human chorionic gonadotropin (HCG) to breast cancer patients who were free of any recurrence and, 3 or 24 months previously, had undergone prophylactic ovariectomies (5 and 4 patients, respectively). In 5 of these women, the amount of testosterone excreted increased significantly after HGG was administered. We inhibited adrenal androgen secretion in 11 patients, whose presurgical urinary testosterone levels were above normal. After their ovaries were removed, these women received 1.5 mg dexamethaxone (DXM) daily for 30 days at a time, after which the amount of testosterone excreted was evaluated and, if the level was above 5.0 mug/24 hours, therapy was repeated for another 30 days. Of the patients who showed objective remission after ovarietomies, there were 4 (26.3%) of 15 who had normal androgen excretion levels; 8 (57.1%) of 14 had increased amounts and were treated by surgery alone; and 10 (90.9%) of 11 received a combination of ovariectomies and DXM therapy. The duration of regression was the highest in the latter group.
Local radiotherapy and granulocyte-macrophage colony-stimulating factor to generate abscopal responses in patients with metastatic solid tumours: a proof-of-principle trial
Authors: Encouse B Golden, Arpit Chhabra, Abraham Chachoua, Sylvia Adams, Martin Donach, Maria Fenton-Kerimian, Kent Friedman, Fabio Ponzo, James S Babb, Judith Goldberg, Sandra Demaria, Silvia C Formenti
Journal: The Lancet Oncology (2015)
Close Surveillance with Long-Term Follow-up of Subjects with Preinvasive Endobronchial Lesions
Authors: Robert A. A. van Boerdonk, Illaa Smesseim, Daniëlle A. M. Heideman, Veerle M. H. Coupé, Darryl Tio, Katrien Grünberg, Erik Thunnissen, Peter J. F. Snijders, Pieter E. Postmus, Egbert F. Smit, Johannes M. A. Daniels, Thomas G. Sutedja
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Autofluorescence bronchoscopy (AFB) and computed tomography (CT) enable lung cancer (LC) detection at the early (pre-)invasive stage. However, LC risk in patients with preinvasive endobronchial lesions is unclear.To assess LC incidence and identify potential risk determinants in patients with preinvasive lesions.In our tertiary care referral center, 164 subjects with preinvasive lesions were monitored up to 12.5 years by repeated AFB and CT. Occurrence of LC was monitored. Clinical management depended on histological grade, with cancer patients receiving standard care. Potential risk determinants (smoking status, baseline histology, cancer history, and chronic obstructive pulmonary disease [COPD] status) were evaluated in relation to cancer occurrence, event-free survival (EFS), and overall survival (OS).During surveillance (median of 30 mo, range 4-152) of 164 subjects with preinvasive lesions (80 high grade and 84 low grade at inclusion), 61 LCs were detected in 55 subjects (median time to event 16.5 mo). Twenty-three LCs (38%) were detected by CT, and 38 (62%) were detected by AFB. More cancers (36 of 61; 59%) developed from separate, rather than initial lesional sites. Subjects with high-grade lesions were more likely to be diagnosed with LC at the same or another site in the lungs than those with low-grade lesions (P = 0.03). Independent risk determinants for OS were previous curatively treated cancer and COPD (P ≤ 0.05).Presence of preinvasive lesions, especially high-grade lesions, may serve as LC risk markers. LCs occur both at preinvasive lesion sites and elsewhere in the bronchial epithelium or lung parenchyma. Prospective validation of biomarkers and randomized intervention studies are needed to determine optimal management strategies.
Aerobic training reverses the inhibition in the expression of glucocorticoid receptors and decreases the Th2 allergic inflammation in asthma model
Authors: Ronaldo Aparecido Silva, Francine Maria Almeida, Clarice Rosa Olivo, Beatriz Mangueira Saraiva, Milton Arruda Martins, Celso Ricardo Fernandes Carvalho
Journal: European Respiratory Journal (2013)

Aerobic training (AT) reduces the use of corticosteroids by asthmatics; however the anti-inflammatory effects are poorly known. Aim: Investigate the effect of AT in the expression of glucocorticoid receptor (GR) in an asthma animal model. Method: 96 Balb/c mice were divided in 4 groups (n=24 each): Control (CT), AT, Ovalbumin(OVA), OVA+AT. OVA groups received i.p. OVA+Al(OH)-3 and OVA-inhalations that continued during AT. AT (50% max. exercise capacity; 60 min.; 5 x week) begun after chronic airway inflammation and it was performed for 1, 3 or 7 days. After euthanasia, it was analyzed the expression of GR in the airway smooth muscle (ASM); eosinophil counting (BALF); and expression of IL-4, IL-5, NF-kB, eotaxin and RANTES by immunohistochemistry in tissue lung slices. Airway remodeling was quantified by ASM and epithelium thickness and collagen fiber content by image analysis. Results: OVA reduced the expression of GR and increased the eosinophil migration, expression of Th2 cytokines, and airway remodeling (p
Mitochondrial Reactive Oxygen Species at the Heart of the Matter
Authors: Opher S. Kornfeld, Sunhee Hwang, Marie-Hélène Disatnik, Che-Hong Chen, Nir Qvit, Daria Mochly-Rosen
Journal: Circulation Research (2015)

Reactive oxygen species (ROS) have been implicated in a variety of age-related diseases, including multiple cardiovascular disorders. However, translation of ROS scavengers (antioxidants) into the clinic has not been successful. These antioxidants grossly reduce total levels of cellular ROS including ROS that participate in physiological signaling. In this review, we challenge the traditional antioxidant therapeutic approach that targets ROS directly with novel approaches that improve mitochondrial functions to more effectively treat cardiovascular diseases.
Markers of Endothelial-to-Mesenchymal Transition
Authors: Yi-Chun Xu-Dubois, Julie Peltier, Isabelle Brocheriou, Caroline Suberbielle-Boissel, Arjang Djamali, Shannon Reese, Nuala Mooney, Zela Keuylian, Julien Lion, Nacéra Ouali, Pierre P. Levy, Chantal Jouanneau, Eric Rondeau, Alexandre Hertig
Journal: Journal of the American Society of Nephrology (2015)

Antibody-mediated rejection (ABMR) is a leading cause of allograft loss. Treatment efficacy depends on accurate diagnosis at an early stage. However, sensitive and reliable markers of antibody-endothelium interaction during ABMR are not available for routine use. Using immunohistochemistry, we retrospectively studied the diagnostic value of three markers of endothelial-to-mesenchymal transition (EndMT), fascin1, vimentin, and heat shock protein 47, for ABMR in 53 renal transplant biopsy specimens, including 20 ABMR specimens, 24 cell-mediated rejection specimens, and nine normal grafts. We validated our results in an independent set of 74 unselected biopsy specimens. Endothelial cells of the peritubular capillaries in grafts with ABMR expressed fascin1, vimentin, and heat shock protein 47 strongly, whereas those from normal renal grafts did not. The level of EndMT marker expression was significantly associated with current ABMR criteria, including capillaritis, glomerulitis, peritubular capillary C4d deposition, and donor-specific antibodies. These markers allowed us to identify C4d-negative ABMR and to predict late occurrence of disease. EndMT markers were more specific than capillaritis for the diagnosis and prognosis of ABMR and predicted late (up to 4 years after biopsy) renal graft dysfunction and proteinuria. In the independent set of 74 renal graft biopsy specimens, the EndMT markers for the diagnosis of ABMR had a sensitivity of 100% and a specificity of 85%. Fascin1 expression in peritubular capillaries was also induced in a rat model of ABMR. In conclusion, EndMT markers are a sensitive and reliable diagnostic tool for detecting endothelial activation during ABMR and predicting late loss of allograft function.
Treatment of Myelodysplastic Syndrome: Questions Raised by the Azacitidine Experience
Authors: Hagop M. Kantarjian
Journal: Journal of Clinical Oncology (2002)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.10.2415 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12011118 Treatment of Myelodysplastic Syndrome: Questions Raised by the Azacitidine Experience Hagop M. KantarjianxHagop M. KantarjianSearch for articles by this author Show More The University of Texas M.D. Anderson Cancer Center, Houston, TX https://doi.org/10.1200/JCO.2002.20.10.2415 Full Text PDF Figures and Tables "Treatment of Myelodysplastic Syndrome: Questions Raised by the Azacitidine Experience." Journal of Clinical Oncology, 20(10), pp. 2415–2416© 2002 by American Society of Clinical Oncology
Frequency of tuberculosis on bronchial anthracosis, systematic review and meta-analysis
Authors: Majid Mirsadraee, Ahmad Saffari, Mahhamad Sarfraz, Mojtaba Meshkat
Journal: European Respiratory Journal (2011)

Introduction:  Anthracosis is the black pigment discoloration of bronchi which may cause bronchial obstruction. The objective of this study was to collect the data about the association of tuberculosis and anthracosis of lung by systematic review and meta-analysis.   Materials and methods:  All studies that had enough information about frequency of tuberculosis in anthracosis (anthracofibrosis) patients and non-anthracotic control group were enrolled in meta-analysis. Tuberculosis should be confirmed by microbiological (smear or culture) or histopathological methods.   Results:  Twelve studies (8 studies on anthracofibrosis and 4 studies on anthracosis as a general term) comprise of 6280 patients were entered in this meta-analysis. Frequency of tuberculosis in all anthracosis subjects was 22.5% (32.6% for anthracofibrosis and 17.25% for anthracosis) which were significantly higher than control group. Determination of risk showed that cumulated odds ratio of tuberculosis in all studies of anthracosis was 3.16 (95% CI= 2.49-6.85) which revealed significantly higher risk than control group Subgroups analysis showed cumulated odds ratio of tuberculosis in subgroups of anthracofibrosis (3.28; 95% CI=2.16-9.12) were significantly higher than anthracosis as a general term (2.85; 95% CI=1.73-6.61).   Conclusion:  Association of tuberculosis with all type of anthracosis of lung was confirmed and further investigation is not recommended.