tbuckley/cabot-search huggingface dataset:
Abstract 18448: Ckit Marks Cardiac Neural Crest Progenitors in the Developing Mouse Heart
Authors: Konstantinos Chatzistergos, Lauro M Takeuchi, Dieter Saur, Barbara Seidler, Wayne Balkan, Rosemeire O Kanashiro-Takeuchi, Joshua M Hare
Journal: Circulation (2013)

Introduction: Cardiac stem cells expressing the receptor tyrosine kinase c-Kit are a promising cell-based therapy for heart regeneration. However, there is ongoing controversy regarding the embryogenic origins and identity of these cells. We addressed this issue by using a tamoxifen-inducible cKitCreERT2/+ allele to establish the genetic fate-map of c-Kit in the developing mouse heart. Hypothesis: c-Kit marks an embryonic myocardial progenitor cell population which contributes extensively to mammalian cardiogenesis. Methods: cKitCreERT2/+ mice were crossed with R26RLacZ or IRG Cre-reporter mice. To induce recombination in c-Kit expressing cells, females pregnant with cKitCreERT2/R26RLacZ or cKitCreERT2/IRG fetuses were administered intraperitoneal injections of tamoxifen (100μl of 20mg/ml) from 7.5-8.5 (n=10) or 9.5-12.5 (n=15) days post coitum (dpc). Embryos were analyzed at 18.5dpc. Results: Confocal analysis, as well as x-gal staining, revealed that during 7.5-8.5dpc (the period which first and second heart field myocardial progenitors contribute to cardiogenesis) few to no labeled cells were seen in the heart, indicating that c-Kit does not mark progenitors of the cardiogenic mesoderm. In contrast, there was extensive cardiomyogenic contribution from cells expressing c-Kit during 9.5-12.5dpc. A mean of 171.4±21 c-Kit derivatives/field were detected throughout the myocardium [cells/field: 15.2±5.5 in outflow tract (OFT); 5.8±1.0 in left atrium; 16.1±4.7 in right atrium; 39.4±6.3 in right ventricle; 30.1±3.8 in left ventricle; 72.6±11.0 in interventricular septum], ~30% of which were cardiomyocytes (48.1±5.8 per field). Importantly, c-Kit contributed to all expected cardiac neural crest derivatives, including OFT, cardiac and aortic valves, cardiac conduction system, epicardium, endocardium and myocardium. Consistent with a neural crest origins, contribution to endothelium and smooth muscle of the OFT was documented, although coronary vascular cell differentiation was not observed Conclusions: Collectively, our findings strongly support that adult c-Kit+ CSCs are postnatal derivatives of c-Kit+ cardioblasts of neural crest origin, an original source of cardiomyocytes during cardiogenesis.
Altered immunological reactivity in alveolar macrophages from patients with sarcoidosis
Authors: RB Gallagher, M Guckian, A van Breda, C Odlum, MX Fitzgerald, C Feighery
Journal: European Respiratory Journal (1988)

Lung macrophages may play an important role in the pathogenesis of pulmonary sarcoidosis. In this study, the ability of pulmonary macrophages and blood monocytes from sarcoidosis patients, normal controls and disease controls to provide the accessory signal necessary for the concanavalin A-induced activation of normal blood T cells was examined. Blood monocytes from all groups supplied a significantly greater accessory signal than lung macrophages. The accessory capacity of lavage macrophages from sarcoidosis patients varied over a wide range and correlations were sought between these values and other parameters of disease activity. Whilst there was no correlation with clinical parameters, accessory function of alveolar macrophages correlated significantly with the percentage of T helper cells in bronchoalveolar lavage (BAL) fluid (p less than 0.05) and, more closely, with the T helper:T suppressor ratio in BAL fluid (p less than 0.01). This interrelationship between macrophage activity and the T cell infiltrate favours the probability that both cell types participate in the sarcoid disease process and raises the possibility that T cells of both helper and suppressor phenotypes contribute to the pathogenesis.
Fluorescent Probe Study of DNA Conformation in Briefly Heated Human Squamous Cells: Brief Communication 2
Authors: Daniel Roth
Journal: JNCI Journal of the National Cancer Institute (1978)

Journal Article Fluorescent Probe Study of DNA Conformation in Briefly Heated Human Squamous Cells: Brief Communication Get access Daniel Roth Daniel Roth 3Institute for Dental Research, New York University Dental Center, 339 East 25th St., New York, N.Y. 10010. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 60, Issue 1, January 1978, Pages 97–99, https://doi.org/10.1093/jnci/60.1.97 Published: 01 January 1978 Article history Received: 05 July 1977 Accepted: 29 July 1977 Published: 01 January 1978
No additional diagnostic gain of mediastinoscopy following sytematically and thouroughly performed mediastinal staging by EBUS-TBNA
Authors: Axel Kempa, Joao Pedro Steinhauser Motta, Franz Stanzel
Journal: European Respiratory Journal (2014)

Mediastinal staging by EBUS-TBNA is recommended by guidelines to confirm suspected nodal involvement, but mediastinoscopy, if EBUS-TBNA is negative. We reviewed our clinical data to assess the diagnostic value of our routine mediastinal staging.  A systematic biopsy of the mediastinal lymphnode zones was intended in every patient with either a central lesion or a suspected hilar or mediastinal involvement on imaging. Every procedure was performed as a rigid bronchoscopy under general aneaesthesia.  Between January 2010 and December 2011 EBUS-TBNA was performed in 192 patients, who underwent radical surgery and systematic lymphadenectomy later. On average, 2,89 lymphnode zones/ patient were biopsied. In 57% of the patients a systematic lymphnode sampling was performed (including at least lymph node zones 4L, 4R and 7).  33/ 192 patients had a N2-situation on EBUS-TBNA, that was confirmed by systematic lymphadenectomy. 1 patient was EBUS false positive (pN0), and two patients were EBUS false negative (pN2 at lymph node zone 5/6L). The sensitivity for mediastinal involvement was 93,93%, the specifity 99,81% and the negative predictive value was 99,6%.  Mediastinoscopy was performed in 13 patients, in whom PET and CT scanning were suggestive of mediastinal involvement and EBUS-TBNA was negative. The preoperative N-staging was confirmed in all 13 patients, although a N2 stage was found on systematic lymphadenectomy in 2 patients.  EBUS-TBNA, if performed systematically and thoroughly, offers a high negative predictive value. Mediastinoscopy did not improve the sensitivity of preoperative mediastinal staging in our patients and seems to be dispensable.
Post-Transplantation Development of Malignant Lymphoma, an Experimental Model: Syngeneic Lymph Node Transplants
Authors: A E Goldsmith, G F Ryan, A B Joseph
Journal: Journal of the Royal Society of Medicine (1980)

Previously, malignant lymphomas in mice have been found to be the late sequelae of the autologous transplantation of skin grafts pretreated with CO(2); these did not occur with grafts cultured in air alone. The clinical result in this autologous system reflects environmental differences in vitro (Goldsmith & Narvaez 1975). In the present study the syngeneic transplantation in BALB/c mice of lymph node tissue resulted in the late appearance of malignant lymphomas (48-69%), irrespective of the pretransplantation treatment of the grafts. Lymph node grafts were exposed to three different environments before transplantation into syngeneic hosts: (1) to culture in air (24 hours); (2) to culture in an atmosphere of 45% CO(2) in air (24 hours); (3) direct transplantation without in vitro exposure. Transplantation of these three groups of differently treated grafts was followed by the same clinical results in their recipients. These were: (1) The development of lymphoma whereas the spontaneous incidence was zero. (2) The proliferation of T-lymphocytes in the spleen; the incidence of this abnormality correlates with the lymphoma incidence. (3) A higher than normal occurence of immune-associated lesions (amyloidosis, interstitial nephritis and myocarditis). Both syngeneic and autologous transplantations may serve as animal models for the study of clinical malignant lymphoma.
A Reactive Oxygen Species–Mediated Loop Maintains Increased Expression of NADPH Oxidases 2 and 4 in Skin Fibroblasts From Patients With Systemic Sclerosis
Authors: Tatiana Spadoni, Silvia Svegliati Baroni, Donatella Amico, Lisa Albani, Gianluca Moroncini, Enrico V. Avvedimento, Armando Gabrielli
Journal: Arthritis & Rheumatology (2015)

Objective Reactive oxygen species (ROS) contribute to the pathogenesis of fibrosis in systemic sclerosis (SSc; scleroderma), and NADPH oxidase (NOX) is an important source of ROS. Since the role of single NOX isoforms has not been previously investigated in SSc, this study was undertaken to assess the expression of NOX in SSc fibroblasts compared to normal healthy cells and to analyze their role in cell activation. Methods Expression of NOX isoforms in dermal fibroblasts from patients with SSc and healthy control subjects was analyzed by real‐time polymerase chain reaction, immunoblotting, and immunofluorescence. NOX isoforms were silenced using small interfering RNA. Production of ROS was measured by fluorometry and confocal microscopy. Results Scleroderma fibroblasts showed up‐regulation of NOX‐2 and NOX‐4 protein and messenger RNA (mRNA) expression. Treatment of the cells with diphenyleneiodonium, a nonselective inhibitor of flavin‐containing enzymes, and silencing of NOX2 and NOX4 decreased the production of ROS as well as the expression of type I collagen and α‐smooth muscle actin in SSc fibroblasts. ROS generated by NOX‐2 and NOX‐4 were involved in DNA damage and activation of a DNA repair checkpoint. Incubation of healthy control fibroblasts with platelet‐derived growth factor (PDGF) or with IgG isolated from SSc patient serum enhanced the expression of NOX2 and NOX4 mRNA, via ROS, in a time‐dependent manner. Treatment with actinomycin D, a transcription inhibitor, reversed the effects of PDGF stimulation but not the effects of SSc IgG. Conclusion Both NOX2 and NOX4 generate ROS in SSc fibroblasts and play a critical role in cell activation and DNA damage. Expression of NOX‐2 and NOX‐4 in SSc fibroblasts is maintained by a ROS‐mediated loop.
A conversation with Oliver Smithies
Authors: Ushma S. Neill
Journal: Journal of Clinical Investigation (2015)

Professor Oliver Smithies is the Weatherspoon Eminent Distinguished Professor of Pathology and Laboratory Medicine at the University of North Carolina, Chapel Hill. Along with Mario Capecchi and Martin Evans, Oliver was awarded the Nobel Prize in Medicine in Physiology or Medicine in 2007 for his contributions to the development of gene targeting using homologous recombination in embryonic stem cells. This technique has had an immense impact on biomedical research over the past two decades. Professor Smithies has had a long and distinguished career as a researcher and mentor. Here, he provides an entertaining and enlightening discussion of his life in science.
The profile of platelet α‐granule released molecules affects postoperative liver regeneration
Authors: Patrick Starlinger, Stefanie Haegele, Florian Offensperger, Lukas Oehlberger, David Pereyra, Julia B Kral, Waltraud C. Schrottmaier, Sigrun Badrnya, Thomas Reiberger, Arnulf Ferlitsch, Judith Stift, Florian Luf, Christine Brostjan, Thomas Gruenberger, Alice Assinger
Journal: Hepatology (2015)

Platelets promote liver regeneration through site‐specific serotonin release from dense granules, triggering proliferative signaling in hepatocytes. However, the effects of factors derived from platelet α‐granules on liver regeneration are unclear, because α‐granules contain bioactive molecules with opposing functions. Because α‐granule molecules are stored in separate compartments, it has been suggested that platelets selectively release their α‐granule content dependent on the environmental stimulus. Therefore, we investigated the pattern of circulating α‐granule molecules during liver regeneration in 157 patients undergoing partial hepatectomy. We measured plasma levels of α‐granule‐derived factors in the liver vein at the end of liver resection, as well as on the first postoperative day. We observed a rapid accumulation of platelets within the liver after induction of liver regeneration. Platelet count and P‐selectin (a ubiquitous cargo of α‐granules) were not associated with postoperative liver dysfunction. However, low plasma levels of vascular endothelial growth factor (VEGF), but high levels of thrombospondin 1 (TSP‐1), predicted liver dysfunction after resection. Patients with an unfavorable postoperative α‐granule release profile (high TSP‐1/low VEGF) showed substantially worse postoperative clinical outcomes. The unfavorable postoperative α‐granule release profile was associated with increased postoperative portal venous pressure and von Willebrand factor antigen levels as a marker for intrahepatic endothelial dysfunction. Conclusion : The postoperative profile of circulating platelet‐derived factors correlates with the ability of the remnant liver to regenerate. Portal venous pressure and intrahepatic endothelial dysfunction might account for the selective granule release profile. Selective modulation of platelet α‐granule release in patients may represent an attractive target for therapeutic interventions to improve liver regeneration and clinical outcomes after partial hepatectomy. (H epatology 2016;63:1675‐1688)
A cross-sectional study examining inpatients' metered dose inhaler technique and the impact of assessment and education on its effective use
Authors: Judith Jade, Janet Lee, S. Fayyaz Hussain
Journal: European Respiratory Journal (2012)

Introduction : Metered dose inhalers (MDI) are often prescribed during hospital admission. MDI technique influences clinical effectiveness, yet inpatient assessment and education regarding this skill may not happen routinely.   Objectives : We hypothesised that a) inpatients on an acute medical ward often have poor MDI technique and b) simple assessment and education could improve MDI technique.   Methods : A cross-sectional study was conducted on inpatients prescribed an MDI on an acute medical ward during the month of October 2011. Technique was assessed using an Aerosol Inhalation Monitor, by a Health Care Assistant (HCA) trained in its use. Patients with poor technique had simple training and assessment was repeated.   Results : A total of 38 patients were studied (M:F=1.1:1, Age range=40-91). Initial assessment showed only seven patients (18.4%) were able to use the device effectively. The 31 patients (81.5%) that failed initial assessment had simple education regarding technique, and of these eight (25.8%) were then able to successfully use the MDI. Out of the 23 patients that failed reassessment, even after education, 10 (43.5%) were unable to  “synchronise”  administration of medication and a spacer was prescribed. The remaining 13 patients (56.5%) that failed reassessment were unable to use an MDI even with a spacer device.   Conclusions : The majority of inpatients prescribed an MDI were unable to use the device effectively. Basic education and inhaler adjuncts addressed many of the difficulties with MDI usage in this patient group. HCA led assessment of inhaler technique appears to be an invaluable tool in tailoring the use of MDI.
Successful En-Bloc Resection of Large Superficial Tumors in the Stomach and Colon Using Sodium Hyaluronate and Small-Caliber-Tip Transparent Hood
Authors: H Yamamoto, H Kawata, K Sunada, A Sasaki, K Nakazawa, T Miyata, Y Sekine, T Yano, K Satoh, K Ido, K Sugano
Journal: Endoscopy (2003)

En-bloc resection is desirable for accurate histopathological assessment of tissue specimens obtained using endoscopic mucosal resection (EMR). A new EMR method using sodium hyaluronate and a small-caliber-tip transparent hood has been developed. This is a peeling-off method using a needle-knife for mucosal and submucosal incisions. Long-lasting submucosal thickening resulting from an injection of sodium hyaluronate, and good visualization of the submucosal tissue with the aid of a small-caliber-tip transparent hood, make the cutting procedures easy and safe. A large superficial gastric cancer and a large villous tumor of the sigmoid colon were endoscopically resected using this method. En-bloc endoscopic resection was successful in both patients. The gastric lesion was an well-differentiated intramucosal adenocarcinoma, completely resected in a specimen measuring 97 × 50 mm. The colonic lesion was an intramucosal well-differentiated adenocarcinoma in adenoma, completely resected in a specimen measuring 70 × 55 mm in diameter. No significant complications were noted in either patient. The new method of EMR using sodium hyaluronate and the small-caliber-tip transparent hood is a promising method for endoscopic en-bloc resection of large superficial neoplastic lesions, both in the stomach and the colon.
Damage Control as a Strategy to Manage Postreperfusion Hemodynamic Instability and Coagulopathy in Liver Transplant
Authors: Joseph DiNorcia, Minna K. Lee, Michael P. Harlander-Locke, Victor Xia, Fady M. Kaldas, Ali Zarrinpar, Douglas G. Farmer, Hasan Yersiz, Jonathan R. Hiatt, Ronald W. Busuttil, Vatche G. Agopian
Journal: JAMA Surgery (2015)

Damage control (DC) with intra-abdominal packing and delayed reconstruction is an accepted strategy in trauma and acute care surgery but has not been evaluated in liver transplant.To evaluate the incidence, effect on survival, and predictors of the need for DC using intra-abdominal packing and delayed biliary reconstruction in patients with coagulopathy or hemodynamic instability after liver allograft reperfusion.We performed a retrospective analysis of adults undergoing liver transplant at a large transplant center from February 1, 2002, through July 31, 2012.Predictors of DC, effects on graft, and patient survival.Of 1813 patients, 150 (8.3%) underwent DC during liver transplant, with 84 (56.0%) requiring a single additional operation for biliary reconstruction and abdominal closure and 57 (38.0%) requiring multiple additional operations. Compared with recipients without DC, patients requiring DC had greater Model for End-stage Liver Disease scores (33 vs 27; P < .001); more frequent pretransplant hospitalization (72.0% vs 47.9%; P < .001), intubation (33.3% vs 19.9%; P < .001), vasopressors (23.2% vs 10.9%; P < .001), renal replacement therapy (49.6% vs 30.3%; P < .001), and prior major abdominal operations (48.3% vs 21.9%; P < .001), including prior liver transplant (29.3% vs 8.9%; P < .001); greater operative transfusion requirements (37 vs 13 units of packed red blood cells; P < .001); worse intraoperative base deficit (10.3 vs 8.4; P = .03); more frequent postreperfusion syndrome (56.2% vs 27.3%; P < .001); and longer cold (430 vs 404 minutes; P = .04) and warm (46 vs 41 minutes; P < .001) ischemia times. Patients who underwent DC followed by a single additional operation for biliary reconstruction and abdominal closure had similar 1-, 3-, and 5-year graft survival (71%, 62%, and 62% vs 81%, 71%, and 67%; P = .26) and patient survival (72%, 64%, and 64% vs 84%, 75%, and 70%; P = .15) compared with recipients not requiring DC. Multivariate predictors of DC included prior liver transplant or major abdominal operation, longer pretransplant recipient and donor length of stay, greater Model for End-stage Liver Disease score, and longer warm and cold ischemia times (C statistic, 0.75).To our knowledge, this study represents the first large report of DC as a viable strategy for liver transplant recipients with coagulopathy or hemodynamic instability after allograft reperfusion. In DC recipients not requiring additional operations, outcomes are excellent and comparable to 1-stage liver transplant.
Clinical significance of p53 mutations in newly diagnosed Burkitt's lymphoma and acute lymphoblastic leukemia: a report of 48 cases.
Authors: C Preudhomme, I Dervite, E Wattel, M Vanrumbeke, M Flactif, J L Lai, B Hecquet, M C Coppin, B Nelken, B Gosselin
Journal: Journal of Clinical Oncology (1995)

To correlate the presence of p53 mutations and initial characteristics, response to chemotherapy, and survival in newly diagnosed Burkitt's lymphoma (BL) and Burkitt's acute lymphoblastic leukemia (L3 ALL).Forty-eight patients with newly diagnosed BL or L3 ALL, most of whom were treated with very intensive regimens, including early CNS disease treatment, were studied. Detection of p53 mutations was made by single-strand conformation polymorphism (SSCP) analysis of exons 5 to 8 of the gene, and mutations were determined by direct sequencing of exons with abnormal SSCP findings. Comparison of outcome between mutated and nonmutated cases was made in all patients and also after excluding five patients who received therapeutic regimens considered as suboptimal and one patient who died of AIDS while in complete remission (CR), as those six patients had no p53 mutations.A point mutation was found in nine patients (19%), and consisted of a missense mutation in seven and a chain-terminating mutation in two. SSCP, sequence, and cytogenetic analysis strongly suggested that eight of nine patients with mutations had retained the normal p53 allele, which had been lost in the remaining patient. These findings were confirmed by fluorescence-in-situ hybridization (FISH) with a p53-specific probe in two patients, including the one who had lost the normal p53 allele. Unexpectedly, mutations were significantly less frequent in patients with disseminated disease, ie, L3 ALL or stage IV BL (four of 35, 11%), than in more localized forms, ie, BL stage I, II, or III (five of 13, 38%) (P = .03). CR rates were similar in mutated (78%) and nonmutated cases (78%). The actuarial disease-free interval (DFI) after 12 months and actuarial survival rates after 24 months were 49% and 66%, respectively, in patients with mutations, and 73% and 48%, respectively, those without mutations. The differences were not significant.Our findings suggest that, contrary to what is seen in most other neoplasias, p53 mutations in newly diagnosed BL and L3 ALL are not associated with extensive tumor mass or poor response to intensive therapeutic regimens. It is hypothesized that this difference with most tumors could be due to the fact that p53 mutations in BL and L3 ALL are generally associated with persistence of a normal residual p53 allele, contrary to what is observed in the majority of tumors.
Is Propionibacterium acnes the cause of sarcoidosis
Authors: S Mukherjee
Journal: Thorax (2004)

▴ Nishiwaki T, Yoneyama H, Eishi Y, et al. Indigenous pulmonary Propionibacterium acnes primes the host in the development of sarcoid-like pulmonary granulomatosis in mice. Am J Pathol2004;165:631–9

[OpenUrl][1][PubMed][2][Web of Science][3]



Sarcoidosis is a chronic granulomatous disorder of unknown aetiology. This study reports the induction in mice of pulmonary granulomas, similar to those in sarcoidosis, by indigenous Propionibacterium acnes residing in the lower respiratory tract. This was associated with an influx of P acnes sensitised CD4+ T lymphocytes from the …

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