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Medial Thickening (medial + thickening)
Selected AbstractsDifferent roles of proteolipids and 70-kDa subunits of V-ATPase in growth and death of cultured human cellsGENES TO CELLS, Issue 6 2003Hong Zhan Background: The vacuolar-type proton-translocating adenosine triphosphatase (V-ATPase) plays important roles in cell growth and tumour progression. V-ATPase is composed of two distinct structures, a hydrophilic catalytic cytosolic sector (V1) and a hydrophobic transmembrane sector (V0). The V1 sector is composed of 5,8 different subunits with the structure A3B3C1D1E1F1G1H1. The V0 sector is composed of 5 different subunits with the structure 1161381191166. The over-expression of 16-kDa proteolipid subunit of V-ATPase in the perinuclear region of the human adventitial fibroblasts promotes phenotypic modulation that contributes to neointimal formation and medial thickening. A relationship between oncogenicity and the expression of the 16-kDa proteolipid has also been suggested in human pancreatic carcinoma tissue. Results: We found that the mRNA levels of the 16-kDa proteolipid but not of the 70-kDa subunit of V-ATPase in human myofibroblasts were more abundant in serum-containing medium (MF(+) cells) than serum-free medium (MF(,) cells). In HeLa cells, the levels of mRNA and protein of the 16-kDa, 21-kDa or 70-kDa were clearly suppressed when the corresponding anti-sense oligonucleotides were administered to the culture medium. The growth rate and viability (mostly due to necrosis) of HeLa cells were reduced markedly by the 16-kDa and 21-kDa anti-sense, but little by the 70-kDa anti-sense, and not at all by any sense oligonucleotides. The localization of 16-kDa/21-kDa proteolipid subunits was different from that of the 70-kDa subunit in HeLa cells. Conclusion: These results suggest that the 16-kDa and 21-kDa proteolipid subunits of the V0 sector play crucial roles in growth and death of cultured human cells. Our results may provide new insights into the mechanism and therapeutic implications for vessel wall hyperplasia and tumorigenesis. [source] Biodegradable External Stents Inhibit Saphenous Vein Graft Thickening in the PigJOURNAL OF CARDIAC SURGERY, Issue 6 2002P Gadsdon Aim: External, non-restrictive, macro-porous stents prevent neointima formation in porcine vein grafts and have been proposed as a therapeutic approach to the prevention of late vein graft failure. Since these stents are non-biodegradable and therefore may elicit deleterious long-term, inflammatory, infective and mechanical complications the effect of external macro-porous biodegradable (polyglactin) stents on neointimal and medial thickening in porcine vein grafts was investigated. Methods: Bilateral vein saphenous vein-carotid artery interposition grafting was performed in Large White pigs (22,36 kg, n = 6) with external placement of 8 mm diameter polyglactin stents on one side, the contralateral side acting as a control. One month after surgery, graft wall dimensions were measured on histological sections using computer-aided planimetry and immunocytochemistry undertaken for selected parameters. Results: Polyglactin stents significantly reduced medial thickening compared to the All grafts were patent at explantation. Intimal thickness was significantly lower (p < 0.05) in the stented grafts (0.11 ± 0.01 mm) compared to the unstented controls (0.18 ± 0.01 mm). Similarly, medial thickness was significantly lower (p < 0.05) in the stented grafts (0.24 ± 0.03 mm) compared to the unstented controls (0.43 ± 0.04 mm) mm. Grafts externally supported with polyglactin had a pronounced increase in inflammatory cells (in particular, giant cells) around the biodegradable stent compared to both unstented controls and previously studied Dacron stented grafts. The space between graft and stent had become organised into a neo-adventitia with abundant microvessels which stained positively for VEGF and lectin (markers of micorvessels and endothelial cells). Conclusions: An over-size biodegradable stent reduces medial thickening, a component of late vein graft failure in experimental grafts. If subsequent studies confirm the preservation of this beneficial effect when the stent biodegrades completely, this form of stent may have an advantage over permanent stent material in the clinical use of external stenting to prevent vein graft thickening and failure. [source] An autopsy case of Fabry disease with neuropathological investigation of the pathogenesis of associated dementiaNEUROPATHOLOGY, Issue 5 2008Riki Okeda The pathogenesis of dementia associated with Fabry disease was examined neuropathologically in an autopsy case. The patient was a 47-year-old computer programmer who developed renal failure at the age of 36, necessitating peritoneal dialysis, and thereafter suffered in succession episodic pulmonary congestion, bradyacusia, heart failure, and dementia, before dying of acute myocardial infarction. MRI of the brain demonstrated leuko-araiosis. The CNS parenchyma showed widespread segmental hydropic swelling of axons in the bilateral cerebral and cerebellar deep white matter in addition to neuronal ballooning due to glycolipid storage in a few restricted nuclei and multiple tiny lacunae. Hydropic axonal swelling was also sparsely distributed in the pyramidal tract, pedunculus cerebellaris superior and brachium colliculi inferioris, but wallerian degeneration of these tracts was absent. Additional features included angiopathy of the subarachnoidal arteries due to Fabry disease, such as medial thickening resulting from glycolipid deposition in smooth muscle cells (SMCs) and adventitial fibrosis with lymphocytic infiltration, together with widespread subtotal or total replacement of medial SMCs by fibrosis, associated with prominent intimal fibrous thickening and undulation of the internal elastic membrane of medium-sized (1000,100 ,m diameter) arteries. The findings in this case suggest that axonopathic leukoencephalopathy due to multisegmental hydropic swelling of axons in the bilateral cerebral deep white matter is responsible for the dementia associated with Fabry disease, and may be caused by ischemia resulting from widespread narrowing and stiffening of medium-sized subarachnoidal arteries and progressive heart failure. [source] Time-related Histopathologic Changes in Fresh Frozen Carotid Xenografts in a Pig-to-Goat Implantation ModelARTIFICIAL ORGANS, Issue 10 2009Ji M. Chang Abstract We performed an animal experiment with an emphasis on time-related histopathologic changes to evaluate the clinical feasibility of immunologically nontreated xenogenic vascular grafts. Bilateral porcine carotid arteries were harvested, and then, after short-term freezing at ,70°C, interposed into goats' carotid arteries. An antiplatelet agent was administered orally for 3 months postoperatively. The goats were randomly assigned to five periods of observation (1 week, and 1, 3, 6, and 12 months after implantation); two animals were observed at each of these times. Doppler ultrasonography was performed periodically during the observation period. At predetermined times, grafts were explanted and examined using hematoxylin and eosin, and Masson's trichrome stains. Immunohistochemical evaluations were conducted with T-lymphocyte indicator and von Willebrand factor. Two goats died prematurely, one from respiratory problems related to anesthesia and the other from pneumonia. A total of 16 grafts from the remaining eight animals were evaluated. Grafts were all patent except one at 3 months after transplantation. Histologically, xenogenic arterial grafts showed early endothelial cell loss at 1 week. This was followed by a progressive spread of recipient endothelial cells from the anastomotic site, and re-endothelialization was complete at 1 month. The degree of neointimal and medial thickening increased until 3 months, and then decreased. At 12 months, no additional growth of the intimal or medial layers was observed. Adventitial inflammation became severe at 3 months, but was reduced at 6,12 months. The proportions of CD3-positive T-lymphocytes among inflammatory cell infiltrations were very low. Fresh frozen xenogenic arterial grafts showed acceptable patency throughout the 12-month period and showed no evidence of being unduly influenced by rejection reactions. [source] | ||||||||||