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Biomedical subjects

W Mazur

Publications and source records attributed to W Mazur.

At least 55 records · Page 3Linked to original sources
PubMed1996

High dose rate intracoronary radiation for inhibition of neointimal formation in the stented and balloon-injured porcine models of restenosis: angiographic, morphometric, and histopathologic analyses.

PURPOSE: We examined the effects of intracoronary irradiation delivered at a high dose rate on neointimal hyperplasia after injury induced by two methods: balloon overstretch injury, and stent implantation in a porcine model of coronary restenosis. METHODS AND MATERIALS: In 34 Hanford miniature swine, a segment of each coronary artery was targeted for injury and treatment. The artery segments were treated with 192Ir at doses of 10 Gy over 4 min (eight animals), 15 Gy over 6 min (nine animals), 25 Gy over 10 min (nine animals) or control (simulation wire only; eight animals). The treated segments were subjected to stent implantation (left anterior descending and right coronary artery) or balloon overstretch (circumflex) injury. Twenty-eight days later, repeat coronary angiography and sacrifice were done. Quantitative coronary angiography, morphometry, and extensive histopathologic analyses were carried out in a blinded fashion. RESULTS: The change in minimal lumen diameter from postinjury to presacrifice in the stent-injured left anterior descending was -0.79 +/- 0.34 (mean: +/- SD) mm in the control group, compared to -0.43 +/- 0.35 mm in the 15 Gy (p = 0.04) and -0.21 +/- 0.50 mm in the 25 Gy (p = 0.01) groups; and in the balloon-injured circumflex was -0.31 +/- 0.22 mm in the control group compared to -0.03 +/- 0.18 mm in the 10 Gy (p = 0.05) and 0.00 +/- 0.33 in the 15 Gy (p = 0.01) groups. Percent area stenosis in the left anterior descending was 36 +/- 9% in the control group compared to 18 +/- 12% in the 15 Gy (p = 0.003) and 11 +/- 11% in the 25 Gy (p < 0.001) groups; and in the circumflex was 16 +/- 10% in the control groups, compared to 5 +/- 5% in the 15 Gy (p = 0.02) and 2 +/- 2% in the 25 Gy (p = 0.009) groups. Histopathology showed a striking reduction in the amount of neointima in the irradiated arteries compared with control vessels. Other radiation effects were stromal fibrin exudate, thinning of the media, and adventitial fibrosis and leukocyte infiltration in the radiated arterial segments. CONCLUSIONS: High dose rate intracoronary irradiation with 192Ir effectively inhibits intimal proliferation after stent-induced as well as balloon-overstretch injury. This shorter treatment time (4 to 10 min) may provide a clinically practical approach to the prevention of restenosis after angioplasty.

Angioplasty, Balloon, Coronary↗
PubMed1996

Isotope dilution gas chromatographic-mass spectrometric method for the determination of isoflavonoids, coumestrol, and lignans in food samples.

We present a method for the quantitative determination of the phytoestrogens formononetin, biochanin A, daidzein, genistein, and coumestrol and simultaneously the lignans secoisolariciresinol (SECO) and matairesinol in plant-derived foods. These compounds are measured by isotope dilution gas chromatography-mass spectrometry in the selected ion monitoring mode (ID/GC/MS/SIM) using synthesized deuterated internal standards for the correction of losses during the procedure. A three-step hydrolysis--a rehydration with distilled H2O, followed by enzymatic and acid hydrolysis--has been applied in order to convert the diphenolic glycosides into their respective aglycones. Purification and separation are carried out in two ion-exchange chromatographic steps followed by derivatization and GC-MS. The within-assay imprecision values vary 3.1-9.6% and the between-assay imprecision 7.0-21.2%. The mean recovery of authentic standards processed through the whole procedure varied from 95.5 to 105.5%. Values for some different food samples are presented. The simultaneous determination of the biologically most interesting phytoestrogens and lignans in foods has not been carried out previously and the method will be useful for screening of important foods in populations with different risk of cancer and coronary heart disease, and for metabolic studies.

Anion Exchange Resins↗
PubMed1996

Inhibition of coronary restenosis by antithrombin III in atherosclerotic swine.

BACKGROUND: Thrombin-mediated vascular smooth muscle cell proliferation has been implicated in coronary restenosis. Attempts to inhibit this mitogenic activity have recently focused on non-physiologic direct thrombin inhibitors, whereas endogenous thrombin inhibitors such as antithrombin III (ATIII) have received little attention. ATIII is the main physiologic inhibitor of thrombin and may thus be a potential therapeutic agent for prevention of restenosis. METHODS: Human ATIII (125 U/kg) and heparin (200 U/kg) were administered to 12 atherosclerotic swine 30 min prior to inducing restenosis by oversized stent (left anterior descending and right coronary arteries; stent-to-artery ratio approximately 1.2) and balloon injury (circumflex; balloon artery ratio approximately 1.2). Eleven control swine received only heparin every 6 h for 24 h and were subjected to similar stent and balloon injury. Quantitative coronary angiography [change in minimal lumen diameter (delta MLD)] and morphometric analysis [percentage area stenosis (PAS)] were performed 4 weeks later. RESULTS: ATIII activity (mean +/- SD) of treated swine increased from a baseline of 103 +/- 10% to a peak of 266 +/- 48%, whereas trough levels were maintained at 259 +/- 55% for 72 h by drug infusions every 6 h. The delta MLD, the primary angiographic endpoint in the balloon injured vessel was -0.57 +/- 0.33 mm in heparin group versus -0.26 +/- 0.27 mm in the ATIII group (P < or = 0.03). For stented vessels the delta MLD was -0.61 +/- 0.33 mm in the heparin group versus -0.41 +/- 0.37 mm in the ATIII group (P < or = 0.06). The PAS for the balloon injured vessels was 30 +/- 12% in the heparin group versus 19 +/- 14 in the ATIII group (P < or = 0.06). In stented vessels the PAS was 45 +/- 16% in the heparin group versus 38 +/- 16% in the ATIII group (P < or = 0.1). CONCLUSION: Supraphysiologic ATIII levels in combination with heparin inhibits the reduction in MLD in coronary arteries subjected to oversized balloon injury and demonstrates a beneficial trend in arteries subjected to oversized stent injury. These data provide cautious optimism for further investigation with ATIII to prevent coronary restenosis.

Angioplasty, Balloon↗
PubMed1995

[A case of metastasis of the esophageal adenocarcinoma to the middle ear].

The authors have presented the rare case of metastasis the cardiac adenocarcinoma to the middle ear. They have described occurrence of metastatic tumors of the temporal bone, mechanisms of their formation, clinical picture, diagnostic difficulties, prognosis and ways of therapy. A radical surgical treatment and chemotherapy have been used in this case. The patient died 17 months after diagnosis of the cardiac adenocarcinoma and 10 months after diagnosis of metastasis to the temporal bone.

Adenocarcinoma↗
PubMed1995

[Tumors of the submandibular gland].

The authors have analyzed 148 cases with submandibular gland tumors treated surgically in ENT Department of County Hospital Nr 1 in Rzeszów from 1974 to 1994. Inflammatory tumors occurred in 123 (83%) patients, in this number non-specific inflammation caused by calculi occurred in 120 (97.5%) patients and specific inflammations (tuberculosis) in 3 (2.5%) ones. Neoplastic tumors occurred in 14 (56.0%) patients and non-malignant in 11 (44.0%) patients. Among malignant tumors adenoid cystic carcinoma occurs most frequently (8 cases, 57%), whereas among non-malignant ones pleomorphic adenoma is most frequent (10 cases, 91%).

Adolescent↗
PubMed1995

[Neoplasms of the middle ear behind the intact tympanic membrane].

The authors described 4 cases of neoplasms of middle ear behind the intact tympanic membrane (3 cases of paraganglioma and 1 case of adenocarcinoma). They paid attention to the guileful course of disease and non-characteristic symptoms in its initial stage. Only immediate exploratory operation of the middle ear enables to make early diagnosis and start effective treatment.

Adenocarcinoma↗
PubMed1995

[Tumors of the submandibular triangle].

Analysed material consists of 180 patients with different kind of submandibular triangle tumors, excluded disturbances of the submandibular gland. All these patients were treated in ENT Department of County Hospital No 1 in Rzeszów in 1974-1993. Among 180 patients in 97 (54%) cases, the presence of inflammatory tumors were stated: non specific inflammation in 74 (76%) patients and specific inflammation in 23 (24%) patients. In 10 (6%) patients occurred branchial or dermoid cysts. Neoplastic tumors occurred in 73 (40%), malignant tumors in 64 (86%) patients and benign ones in 9 (12%) patients. Among malignant tumors metastatic ones were stated 41 (64%) cases, while primary tumors in 23 (36%). The histology type of tumors were revealed by histology examination.

Adolescent↗
PubMed1994

Fate of side branches after intracoronary implantation of the Gianturco-Roubin flex-stent for acute or threatened closure after percutaneous transluminal coronary angioplasty.

Side branch occlusion may occur in the course of percutaneous transluminal coronary angioplasty (PTCA), particularly if complicated by site dissection. Concern that the additional placement of a stent may further jeopardize side branches is logical. Consequently, this study analyzed pre-PTCA, post-PTCA, poststent, and 6-month follow-up angiograms of 100 consecutive patients in whom 103 Gianturco-Roubin stents were implanted for acute or threatened closure after PTCA. Side branches were defined as major (> 50% of the stented vessel diameter) and minor (< 50%). Minor branches, often < 1 mm in diameter, were assessed only for patency. One hundred eight major branches, of which 33 were diseased (> 50% stenosis), and 129 minor branches were analyzed. Seven major branches (6%), all of which were diseased before PTCA, and 23 minor branches (18%) were lost after PTCA. Immediately after stent insertion, only 1 additional major and 1 minor branch were lost, whereas 2 of 7 major (29%) and 9 of 23 minor (39%) branches reappeared. At follow-up angiography, 7 major branches (6%) were more stenosed and 6 (6%) were improved compared with the angiogram before PTCA. Only 2 major (2%) and 5 minor (4%) branches remained occluded. Additionally, 2 major and 1 minor branch, which were patent after PTCA and stenting, were occluded at follow-up as a result of total occlusion of the stented segment.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1994

Directional atherectomy with the Omnicath: a unique new catheter system.

Omnicath is a directional atherectomy catheter that employs deflecting nontraumatizing wires to anchor the cutting window at the atherectomy site. This anchoring system regulates the depth of cut and provides directional control and distal perfusion. The system continuously removes debris through a suction port from the operative site. To demonstrate the performance of the device, the Omnicath was tested in the external iliac arteries of ten atherosclerotic Hanford miniature swine in which concentric and eccentric lesions were induced. Five animals were sacrificed 3 days after atherectomy; the remaining five animals were sacrificed 6 weeks after the procedure. The acute histology demonstrates depth of cuts varying from partial plaque removal to near full thickness removal of the arterial wall. Histologic sections of the 6 week follow-up group demonstrated minimal healing response. The anchoring wires did not induce either acute injury or neointimal proliferation in the 6 week follow-up period. In conclusion, the Omnicath permits effective and safe atherectomy in this investigative model.

Animals↗
PubMed1994

Comparison of three porcine restenosis models: the relative importance of hypercholesterolemia, endothelial abrasion, and stenting.

BACKGROUND: Porcine models of post-angioplasty restenosis commonly rely on hypercholesterolemia, endothelial abrasion, and intracoronary stenting to induce neointimal thickening. Although stenting clearly induces marked thickening, the influence of pre-stenting endothelial abrasion, and pre- and post-stenting hypercholesterolemia, on the degree and nature of post-stenting neointimal thickening is not clear. In order to assess this influence, we compared the quantity and quality of neointimal thickening in three stented swine restenosis models. METHODS: Twenty-three Hanford miniature swine completed one of three protocols. Model A animals (n = 9) were fed a cholesterol-raising diet, underwent endothelial abrasion of the left anterior descending (LAD) and circumflex (CFX) coronary arteries after 2 weeks on this diet, had balloon-expandable tantalum coil stents placed in the right coronary artery (RCA), LAD, and CFX after 9 weeks on the diet, and were killed 4 weeks later (total of 13 weeks on diet). Model B animals (n = 7) were also fed the cholesterol-raising diet, underwent stenting after 5 weeks on the diet, and were killed 4 weeks later (total of 9 weeks on diet). Model C animals (n = 7) were fed normal swine food, underwent stenting, and were killed 4 weeks later. Endothelial abrasion was not performed in models B and C. RESULTS: Quantitative angiography revealed no significant differences between models in the change of minimal lumen diameter (mm +/- SD) of stented vessels from post-stenting to pre-sacrifice (LAD: 1.05 +/- 0.74, 0.75 +/- 0.62 and 1.05 +/- 0.34; CFX: 1.00 +/- 0.65, 0.83 +/- 0.51 and 1.17 +/- 0.38; RCA: 0.99 +/- 0.35, 0.20 +/- 0.34, and 0.94 +/- 0.80 for models A, B, and C, respectively; all P = NS). Likewise, morphometric analysis showed no differences in percentage area stenosis (% +/- SD) over the same time (LAD: 55 +/- 15, 44 +/- 24, and 42 +/- 16; CFX: 54 +/- 12, 55 +/- 17, and 40 +/- 15; RCA: 39 +/- 20, 34 +/- 11, and 26 +/- 13 for models A, B, and C, respectively; P = NS). The neointima in each model predominantly consisted of smooth muscle cells and collagen matrix. CONCLUSIONS: The degree and nature of coronary artery neointimal thickening 4 weeks after stenting in normolipemic swine are similar to those in stented swine after 9 weeks on a high-cholesterol diet or 13 weeks on a high-cholesterol diet and early endothelial abrasion. The insertion of an intracoronary stent appears to be the major stimulus to neointimal thickening in these swine models of post-angioplasty restenosis.

Angioplasty, Balloon, Coronary↗
PubMed1994

Percutaneous transluminal in vivo gene transfer by recombinant adenovirus in normal porcine coronary arteries, atherosclerotic arteries, and two models of coronary restenosis.

BACKGROUND: Gene therapy has been proposed as a possible solution to the problem of restenosis after coronary angioplasty. The current study was undertaken to assess conventional methods of gene transfer and to develop percutaneous techniques for introducing genes directly into the coronary arteries of large mammals. Since the anticipated targets of gene therapy against restenosis include atherosclerotic and previously instrumented arteries, we also evaluated gene transfer in atherosclerotic coronary arteries and in two porcine models of restenosis: one using intracoronary stents and a second using balloon overstretch angioplasty. METHODS AND RESULTS: The conventional method of using perforated balloon catheters to deliver Lipofectin-DNA complexes directly into the coronary arteries of intact animals was applied to 18 porcine coronary arteries including normal arteries, hypercholesterolemic arteries, and those simulating restenosis. The results of this study were consistent with previously published results indicating that only low levels of luciferase gene expression could be obtained by Lipofectin-mediated gene transfer. We therefore undertook a second, parallel study to evaluate percutaneous transluminal in vivo gene transfer using a replication-deficient adenoviral vector. A comparison of the two studies revealed that the mean level of reporter gene expression in the cohort undergoing adenoviral infection was 100-fold higher than in the cohort undergoing Lipofection. Analysis of luciferase activity over time in normal arteries revealed that recombinant gene expression was half-maximal after 1 day, peaked within 1 week, was still half-maximal at 2 weeks, and declined to low levels by 4 weeks. Histochemical analysis of coronary arteries treated with a second adenovirus expressing a nuclear-localized beta-galactosidase gene demonstrated gene transfer to a limited number of cells in the media and adventitia. Immunohistochemical analysis of Ad5-infused arteries using a monoclonal antibody directed against CD44 identified a periadventitial infiltrate composed of leukocytes. CONCLUSIONS: The recombinant adenoviral vectors proved to be far more effective than Lipofectin at delivering foreign genes directly into the coronary arteries of living mammals. Furthermore, the influences of hypercholesterolemia and arterial injury appeared to have little effect on the levels of gene expression obtained using either method. The results demonstrate that low-level recombinant gene expression, the major obstacle impeding gene therapy for the prevention of restenosis, can potentially be overcome by using adenoviral vectors to mediate coronary gene transfer in vivo. The duration of gene expression provided by these vectors and their effective deployment in atherosclerotic, balloon-overstretched, and stented coronary arteries suggest that recombinant adenovirus may have potential for evaluating gene therapy in the clinically informative porcine models of coronary restenosis.

Adenoviridae↗
PubMed1994

Direct in vivo gene transfer into porcine myocardium using replication-deficient adenoviral vectors.

BACKGROUND: Efficient methods of introducing genes into myocardial cells must be developed before local somatic cell gene therapy can be implemented against myocardial disease. Although adenoviral (Ad5) vectors have been used to target rodent hearts and plasmid DNA has been directly injected into the myocardium of rats and dogs, the amounts of recombinant protein produced by these procedures have not been reported, and adenoviral vectors have not been used in large mammalian hearts. METHODS AND RESULTS: Replication-deficient recombinant adenoviral vectors carrying either the luciferase or lacZ reporter genes were injected directly into the ventricular myocardium of adult domestic swine for evaluation of reporter gene expression. This procedure did not affect regional myocardial function as assessed by systolic wall thickening using ultrasonic crystals. Luciferase activity was detected 3 days after injection, increased markedly at 7 days, and then declined progressively at 14 and 21 days. Luciferase production was comparable in the right and left ventricular walls and increased with increasing amounts of virus, reaching 61 +/- 21 ng at the highest dose examined (3.6 x 10(9) plaque-forming units). The injection of 200 micrograms of plasmid DNA (pRSVL) produced levels of luciferase comparable to 1.8 x 10(8) plaque-forming units of recombinant Ad5; however, when normalized to the number of genes injected, the adenovirus was 140,000 times more efficient than plasmid DNA. Histochemical analysis of beta-galactosidase activity produced by a second Ad5 vector demonstrated that nearly all (> 95%) of the stained cells were cardiomyocytes and that the percentage of cardiomyocytes infected by the virus could be quite high in microscopic regions adjacent to the needle track (up to 75% in fields of 60 to 70 cells); however, Ad5-infected cells were rarely observed farther than 5 mm from the injection site. Furthermore, the Ad5 vector induced pronounced leukocytic infiltration that was far in excess of that seen after injection of vehicle alone. CONCLUSIONS: This study demonstrates for the first time that direct intramyocardial injection of replication-deficient adenovirus can program recombinant gene expression in the cardiomyocytes of a large animal species with relevance to human physiology. The efficiency of adenovirus-mediated gene transfer is far superior to that of plasmid DNA injection, and this method appears to be capable of producing more recombinant protein. However, the cell-mediated immune response to the Ad5 vector and the limited distribution of reporter gene expression suggest that less immunogenic recombinant vectors and more homogeneous administration methods will be required before Ad5 vectors can be successfully used for phenotypic modulation.

Adenoviridae↗
PubMed1994

High-efficiency gene transfer and high-level expression of wild-type p53 in human lung cancer cells mediated by recombinant adenovirus.

A replication-defective and helper-independent recombinant p53 adenovirus was generated. The virus, Ad5CMV-p53, carries an expression cassette that contains human cytomegalovirus E1 promoter, human wild-type p53 cDNA, and SV40 early polyadenylation signal. Four human non-small-cell lung cancer cell lines representing differences in p53 configuration were used to evaluate the Ad5CMV-p53 virus. In the H358 cell line, which has a homozygous deletion of p53, the p53 gene was transferred with 97% to 100% efficiency, as detected by immunohistochemical analysis, when the cells were infected with Ad5CMV-p53 at a multiplicity of infection of 30 to 50 plaque-forming units/cell. Western blots showed that the p53 protein was expressed at a high level. The protein expression peaked at day 3 after infection and lasted for at least 15 days. Growth of the Ad5CMV-p53 virus-infected H358 cells was inhibited 79%, whereas that of noninfected cells or the cells infected with the control virus was not inhibited. Growth of cell line H322, which has a point mutation in p53, was inhibited 72% by Ad5CMV-p53, while that of cell line H460 containing wild-type p53 was less affected (28% inhibition). Tests in nude mice demonstrated that tumorigenicity of the Ad5CMV-p53-treated H358 cells was greatly inhibited. In a mouse model of orthotopic human lung cancer, the tumorigenic H226Br cells, with a point mutation in p53, were inoculated intratracheally 3 days before the virus treatment. Intratracheal instillation of Ad5CMV-p53 prevented tumor formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoviruses, Human↗
PubMed1994

Lipofectin-mediated versus adenovirus-mediated gene transfer in vitro and in vivo: comparison of canine and porcine model systems.

BACKGROUND: Restenosis after coronary angioplasty might be prevented by locally delivered gene therapy in conjunction with percutaneous transluminal coronary angioplasty (PTCA), since this approach should provide a sustained source of therapeutic protein within the dilated lesion. However, the potential application of gene therapy is limited by the technical barrier of efficiently transferring genes to vascular cells. METHODS: We used cultured coronary smooth muscle cells of human, porcine, and canine origin to evaluate three methods of gene transfer: recombinant adenovirus, liposomal complexes (Lipofectin), and Lipofectin supplemented with hemagglutinin. We then compared Lipofectin- and adenovirus-mediated direct gene transfer in canine and porcine coronary arteries. RESULTS: The lipofection of cultured smooth muscle cells was enhanced by adding hemagglutinin, yielding luciferase levels that were 631-fold (human), ninefold (porcine), and sevenfold (canine) higher than with Lipofectin alone. However, the recombinant adenovirus directed even higher levels of gene expression, yielding luciferase levels that were 113,000-fold (human), 450-fold (porcine), and 230-fold (canine) higher than with Lipofectin alone. After percutaneous transluminal local delivery to intact canine coronary arteries, the adenovirus produced 55 times more luciferase than did Lipofectin. In living porcine coronary arteries, adenovirus produced 95 times more luciferase than did Lipofectin. CONCLUSION: Recombinant adenovirus produces far more recombinant protein than does Lipofectin after percutaneous transluminal direct gene transfer to canine and porcine coronary arteries. Adenoviral vectors may therefore prove useful in evaluating the potential of gene therapy in large animal models of coronary restenosis.

Adenoviridae↗
PubMed1994

Coronary restenosis and gene therapy.

Restenosis continues to limit the efficacy of coronary angioplasty, despite the various mechanical and pharmaceutical interventions that have been employed. The migration, proliferation, and extracellular matrix production by vascular smooth muscle cells are processes integral to restenosis, and sustained local delivery of drugs at high concentration should curtail these vascular responses to balloon angioplasty. Our laboratory and others are exploring the potential of using somatic cell gene therapy to provide such treatment and thereby prevent restenosis. However, conventional methods of gene transfer fail to produce physiologic levels of recombinant protein in vivo. This obstacle might be overcome by using adenoviral vectors to mediate efficient direct gene transfer. Herein we summarize these developments and focus upon our laboratory's progress towards evaluating adenovirus-mediated gene therapy in porcine coronary arteries. Recombinant adenoviruses directing the expression of the beta-galactosidase and luciferase reporter genes were evaluated in cultured coronary vascular smooth muscle cells in vitro and in porcine coronary arteries in vivo. Following percutaneous transluminal gene transfer in vivo, recombinant adenoviruses were shown to produce 70- to 240-fold more reporter protein than that produced by Lipofectin-DNA complexes. Furthermore, the high levels of adenovirus-mediated gene expression were shown to persist for at least 14 days following catheterization. Additional histologic studies will be required to determine the cellular distribution of gene expression and to elucidate potential interactions between adenovirus and the host's immune system, but recombinant adenovirus appears to be a promising vector for evaluating gene therapy against coronary restenosis.

Adenoviridae↗
PubMed1993

Amiprilose in the prevention of restenosis after coronary intervention in a swine model.

BACKGROUND: Amiprilose hydrochloride is a synthetic carbohydrate with anti-inflammatory and antiproliferative properties. This study tested the potential benefit of amiprilose in preventing coronary artery restenosis in a swine model. METHODS: The swine restenosis model was prepared using Hanford miniature swine made atherosclerotic with coronary abrasion, high-fat and high-cholesterol feeding, and intracoronary stenting. Eighteen animals were randomized to receive amiprilose, 100 mg/kg body weight orally twice per day (n = 9), or no amiprilose (n = 9) beginning 5 days before stenting and continuing through 4 weeks until sacrifice. Presacrifice quantitative coronary angiography and postsacrifice histologic examination revealed the degree of intimal proliferation. RESULTS: Coronary angiography revealed no difference in percentage-diameter stenosis between the amiprilose and control groups (left anterior descending artery [LAD], 46% +/- 10% vs 44% +/- 17%; circumflex artery [CFX], 43% +/- 21% vs 42% +/- 15%; right coronary artery [RCA], 37% +/- 11% vs 34% +/- 9%; P = not significant [NS]), respectively, or in change in lumen diameter from poststenting to presacrifice (LAD, -1.0 +/- 0.4 mm vs -1.1 +/- 0.7 mm; CFX, -1.2 +/- 0.8 mm vs -1.0 +/- 0.7 mm; RCA, -1.1 +/- 0.4 mm vs -1.0 +/- 0.4 mm; P = NS). Morphometric histologic analysis likewise showed no difference in percentage-area stenosis (LAD, 55% +/- 14% vs 55% +/- 15%; CFX, 53% +/- 15% vs 54% +/- 12%; RCA, 39% +/- 17% vs 39% +/- 20%; P = NS) or in maximal intimal thickness. CONCLUSION: Amiprilose hydrochloride did not prevent coronary intimal proliferation in this swine model of restenosis.

Angioplasty, Balloon, Coronary↗
PubMed1993

Highly efficient gene transfer into adult ventricular myocytes by recombinant adenovirus.

Molecular dissection of mechanisms that govern the differentiated cardiac phenotype has, for cogent technical reasons, largely been undertaken to date in neonatal ventricular myocytes. To circumvent expected limitations of other methods, the present study was initiated to determine whether replication-deficient adenovirus would enable efficient gene transfer to adult cardiac cells in culture. Adult rat ventricular myocytes were infected, 24 h after plating, with adenovirus type 5 containing a cytomegalovirus immediate-early promoter-driven lacZ reporter gene and were assayed for the presence of beta-galactosidase 48 h after infection. The frequency of lacZ+ rod-shaped myocytes was half-maximal at 4 x 10(5) plaque-forming units (PFU) and approached 90% at 1 x 10(8) PFU. Uninfected cells and cells infected with lacZ- virus remained colorless. Beta-galactosidase activity concurred with the proportion of lacZ+ cells and was contingent on the exogenous lacZ gene. At 10(8) PFU/dish, cell number, morphology, and viability each were comparable to uninfected cells. Thus, adult ventricular myocytes are amenable to efficient gene transfer with recombinant adenovirus. The relative uniformity for gene transfer by adenovirus should facilitate tests to determine the impact of putative regulators upon the endogenous genes and gene products of virally modified adult ventricular muscle cells.

Adenoviruses, Human↗