79 research outputs found

    Multiple Paths to Reprogramming

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    Postoperative laryngeal symptoms in a general surgery setting. Clinical study.

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    INTRODUCTION: Vocal cord injuries (VI), postoperative hoarseness (PH), dysphonia (DN), dysphagia (DG) and sore throat (ST) are common complications after general anesthesia; there is actually a lack of consensus to support the proper timing for post-operative laryngoscopy that is reliable to support the diagnosis of laryngeal or vocal fold lesions after surgery and there are no valid studies about the entity of laryngeal trauma in oro-tracheal intubation. Aim of our study is to evaluate the statistical relation between anatomic, anesthesiological and surgical variables in the case of PH, DG or impaired voice register. MATERIALS AND METHODS: 50 patients (30 thyroidectomies, 8 videolaparoscopic cholecistectomies, 2 right emicolectomies, 2 left emicolectomies, 1 gastrectomy, 1 hemorrhoidectomy, 1 nefrectomy, 1 diagnostic videothoracoscopy, 1 superior right lung lobectomy, 1 appendicectomy, 1 incisional hernia repair, 1 low anterior rectal resection, 1 radical hysterectomy) underwent clinical evaluation and direct laryngoscopy before surgery, within 6 hours, after 72 hours and after 30 days, to evaluate motility and breathing space, phonatory motility, true and false vocal folds and arytenoids oedema. We evaluated also mean age (56.6 ± 3.6 years), male:female ratio (1:1.5), cigarette smoke (20%), atopic comorbidity (17/50 = 34%), Mallampati class (32% 1, 38% 2, 26% 3, 2% 4), mean duration of intubation (159 minutes, range 50 - 405 minutes), Cormack-Lehane score (34% 1, 22% 2, 22% 3, 2% 4), difficult intubation in 9 cases (18%). No complication during the laryngoscopy were registered. We investigated the statistic relationship between pre and intraoperative variables and laryngeal symptoms and lesions. RESULTS: In our experience, statistically significant relations were found in prevalence of vocal folds oedema in smokers (p < 0.005), self limiting DG and DN in younger patients (p < 0.005) and in thyroidectomy (p < 0.01), DG after thyroidectomy (p < 0.01). The short preoperative use of steroids and antihistaminic to prevent allergic reactions appears not related to reduction or prevention of DN, DG, PH and ST. No statistical relation in incidence of postoperative complications was found for the prolonged intubation, gastro-esophageal reflux, BURP manoeuvre (backward upward right sided pressure) and Mallampati and Cormack-Lehane class more than 2, maintenance with sevoflurane 2% and use of stilet. CONCLUSIONS: Direct laryngoscopy is essential for the detection of arytenoid lesions after orotracheal intubation for general anesthesia. In our opinion, a part of temporary post-operative DN or PH is due to monolateral or bilateral arytenoids oedema, secondary to prolonged or difficult orotracheal intubation, valuable with laryngoscopy 72 hours after surgery. Is necessary to adjunct these complications in the surgical informed consensus scheme

    Myogenic induction of adult and pluripotent stem cells using recombinant proteins

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    Met Activating Genetically Improved Chimeric Factor 1 (Magic-F1) is a human recombinant protein, derived from dimerization of the receptor-binding domain of hepatocyte growth factor. Previous experiments demonstrate that in transgenic mice, the skeletal muscle specific expression of Magic-F1 can induce a constitutive muscular hypertrophy, improving running performance and accelerating muscle regeneration after injury. In order to evaluate the therapeutic potential of Magic-F1, we tested its effect on multipotent and pluripotent stem cells. In murine mesoangioblasts (adult vessel-associated stem cells), the presence of Magic-F1 did not alter their osteogenic, adipogenic or smooth muscle differentiation ability. However, when analyzing their myogenic potential, mesoangioblasts expressing Magic-F1 differentiated spontaneously into myotubes. Finally, Magic-F1 inducible cassette was inserted into a murine embryonic stem cell line by homologous recombination. When embryonic stem cells were subjected to myogenic differentiation, the presence of Magic-F1 resulted in the upregulation of Pax3 and Pax7 that enhanced the myogenic commitment of transgenic pluripotent stem cells. Taken together our results candidate Magic-F1 as a potent myogenic stimulator, able to enhance muscular differentiation from both adult and pluripotent stem cells. publisher: Elsevier articletitle: Myogenic induction of adult and pluripotent stem cells using recombinant proteins journaltitle: Biochemical and Biophysical Research Communications articlelink: http://dx.doi.org/10.1016/j.bbrc.2015.07.022 content_type: article copyright: Copyright © 2015 The Authors. Published by Elsevier Inc. ispartof: Biochemical and Biophysical Research Communications vol:464 issue:3 pages:755-61 ispartof: location:United States status: publishe

    Generation of a Sprague-Dawley-GFP rat iPS cell line

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    We generated a rat iPSC line called ATCi-rSD95 from transgenic Sprague-Dawley GFP fetal fibroblasts. Established ATCi-rSD95 cells present a normal karyotype, silencing of the transgenes and express pluripotency-associated markers. Additionally, ATCi-rSD95 cells are able to form teratoma with differentiated cells derived from the three germ-layers that maintain the GFP expression

    Isolation and characterization of Sprague-Dawley and Wistar Kyoto GFP rat embryonic stem cells

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    We generated two rat embryonic stem cell (ESC) lines: ATCe-SD7.8 from Sprague-Dawley strain and ATCe-WK1 from Wistar Kyoto strain. Cells were marked with enhanced green fluorescent protein (eGFP) by transduction with a lentiviral vector. Cells present a normal karyotype and express pluripotency-associated markers. Pluripotency was tested in vivo with the teratoma formation assay. Cells maintain eGFP expression upon differentiation to the three-germ layers. These cells can be a useful tool for cell therapy studies and chimera generation as they can be easily tracked by eGFP expression

    Surgical Treatment of Coledochal Cyst Associated with an Aberrant Posterior Hepatic Duct: Report of a Case and Brief Literature Review

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    Choledochal cysts (CCs) are rare congenital cystic or fusiform dilatations of the biliary tree that can involve the extrahepatic and/or intrahepatic biliary tree. We report a case of huge type I CC associated with an aberrant posterior hepatic duct. A 52-year-old man presented with a 3-week history of upper right abdominal pain and jaundice and serologic sign of obstructive jaundice. Ultrasonography (US), magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography were performed with the diagnosis of CC type I according to the classification of Alonso-Lej and Todani-Watanabe. The indication for surgical resection was posed. The cyst was completely resected and the biliary tract was reconstructed with a double hepatico-jejunostomy using the same Roux limb, since during the surgical dissection a before unrecognized anatomical variation of the right biliary tree (aberrant posterior hepatic duct at VI–VII segment) was identified. The diagnosis of CC is often difficult and US and magnetic resonance cholangiopancreatography are necessary to definite biliary dilatation. Endoscopic retrograde cholangiopancreatography should be the most definitive and reliable procedure for the diagnosis and treatment of bilio-pancreatic disorders. Gold standard treatment is surgery (bilio-jejunostomy) and frozen-section histology should be performed to rule out the presence of cancer. In conclusion, surgery is the gold standard for the treatment of CC type I and does not depend on the age of patients, based on a substantial lifetime risk of developing cholangiocarcinoma. Preoperative study is mandatory to assess the biliary tree morphology and to research any anatomical variation

    Cystic mucinous adenocarcinoma of the lung: a case report

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    Mucinous cystic tumors of the lung are uncommon, the preoperative pathologic diagnosis is difficult and their biological behavior is still controversial. We report the case of a patient with a clinically benign cystic lesion that post-operatively showed to be consistent with an invasive adenocarcinoma arising in a mucinous cystadenoma of the lung

    The Renin Angiotensin System (RAS) mediates bifunctional growth regulation in melanoma and is a novel target for therapeutic intervention

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    Despite emergence of new systemic therapies, metastatic melanoma remains a challenging and often fatal form of skin cancer. The renin–angiotensin system (RAS) is a major physiological regulatory pathway controlling salt–water equilibrium, intravascular volume and blood pressure. Biological effects of the RAS are mediated by the vasoactive hormone angiotensin II (AngII) via two receptor subtypes, AT1R (encoded by AGTR1) and AT2R (encoded by AGTR2). We report decreasing expression and increasing CpG island methylation of AGTR1 in metastatic versus primary melanoma and detection in serum of methylated genomic DNA from the AGTR1 CpG island in metastatic melanoma implying that AGTR1 encodes a tumour suppressor function in melanoma. Consistent with this hypothesis, antagonism of AT1R using losartan or shRNA-mediated knockdown in melanoma cell lines expressing AGTR1 resulted in acquisition of the ability to proliferate in serum-free conditions. Conversely, ectopic expression of AGTR1 in cell lines lacking endogenous expression inhibits proliferation irrespective of the presence of AngII implying a ligand-independent suppressor function for AT1R. Treatment of melanoma cell lines expressing endogenous AT2R with either AngII or the AT2R-selective agonist Y6AII induces proliferation in serum-free conditions whereas the AT2R-specific antagonists PD123319 and EMA401 inhibit melanoma growth and angiogenesis and potentiate inhibitors of BRAF and MEK in cells with BRAF V600 mutations. Our results demonstrate that the RAS has both oncogenic and tumour suppressor functions in melanoma. Pharmacological inhibition of AT2R may provide therapeutic opportunities in melanomas expressing this receptor and AGTR1 CpG island methylation in serum may serve as a novel biomarker of metastatic melanoma

    Reversal of hyperglycemia by insulin-secreting rat bone marrow- and blastocyst-derived hypoblast stem cell-like cells

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    β-cell replacement may efficiently cure type 1 diabetic (T1D) patients whose insulin-secreting β-cells have been selectively destroyed by autoantigen-reactive T cells. To generate insulin-secreting cells we used two cell sources: rat multipotent adult progenitor cells (rMAPC) and the highly similar rat extra-embryonic endoderm precursor (rXEN-P) cells isolated under rMAPC conditions from blastocysts (rHypoSC). rMAPC/rHypoSC were sequentially committed to definitive endoderm, pancreatic endoderm, and β-cell like cells. On day 21, 20% of rMAPC/rHypoSC progeny expressed Pdx1 and C-peptide. rMAPCr/HypoSC progeny secreted C-peptide under the stimulus of insulin agonist carbachol, and was inhibited by the L-type voltage-dependent calcium channel blocker nifedipine. When rMAPC or rHypoSC differentiated d21 progeny were grafted under the kidney capsule of streptozotocin-induced diabetic nude mice, hyperglycemia reversed after 4 weeks in 6/10 rMAPC- and 5/10 rHypoSC-transplanted mice. Hyperglycemia recurred within 24 hours of graft removal and the histological analysis of the retrieved grafts revealed presence of Pdx1-, Nkx6.1- and C-peptide-positive cells. The ability of both rMAPC and HypoSC to differentiate to functional β-cell like cells may serve to gain insight into signals that govern β-cell differentiation and aid in developing culture systems to commit other (pluripotent) stem cells to clinically useful β-cells for cell therapy of T1D
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