Biomedical subjects

K Walsh

Publications and source records attributed to K Walsh.

At least 91 records · Page 5Linked to original sources

PubMed2000

Akt1/PKB upregulation leads to vascular smooth muscle cell hypertrophy and polyploidization.

Vascular smooth muscle cells (VSMCs) at capacitance arteries of hypertensive individuals and animals undergo marked age- and blood pressure-dependent polyploidization and hypertrophy. We show here that VSMCs at capacitance arteries of rat models of hypertension display high levels of Akt1/PKB protein and activity. Gene transfer of Akt1 to VSMCs isolated from a normotensive rat strain was sufficient to abrogate the activity of the mitotic spindle cell-cycle checkpoint, promoting polyploidization and hypertrophy. Furthermore, the hypertrophic agent angiotensin II induced VSMC polyploidization in an Akt1-dependent manner. These results demonstrate that Akt1 regulates ploidy levels in VSMCs and contributes to vascular smooth muscle polyploidization and hypertrophy during hypertension.

Angiotensin II↗

PubMed2000

Acute modulation of endothelial Akt/PKB activity alters nitric oxide-dependent vasomotor activity in vivo.

The serine/threonine protein kinase Akt (protein kinase B) phosphorylates endothelial cell nitric oxide synthase (eNOS) and enhances its ability to generate nitric oxide (NO). Because NO is an important regulator of vasomotor tone, we investigated whether Akt can regulate endothelium-dependent vasomotion in vivo using a rabbit femoral artery model of gene transfer. The endothelium of isolated femoral arteries was infected with replication-defective adenoviral constructs expressing beta-galactosidase, constitutively-active Akt (myr-Akt), or dominant-negative Akt (dn-Akt). Femoral arteries transduced with myr-Akt showed a significant increase in resting diameter and blood flow, as assessed by angiography and Doppler flow measurements, respectively. L-NAME, an eNOS inhibitor, blocked myr-Akt-mediated vasodilatation. In contrast, endothelium-dependent vasodilatation in response to acetylcholine was attenuated in vessels transduced with dn-Akt, although these vessels showed normal responses to nitroglycerin, an endothelium-independent vasodilator. Similarly, relaxation of murine aorta ex vivo in response to acetylcholine, but not nitroglycerin, was inhibited by transduction of dn-Akt to the endothelium. These data provide evidence that Akt functions as key regulator of vasomotor tone in vivo.

Acetylcholine↗

PubMed2000

Effect of a 30-minute infusion of dobutamine hydrochloride on hind limb blood flow and hemodynamics in halothane-anesthetized horses.

OBJECTIVE: To evaluate the hemodynamic effects of dobutamine hydrochloride (0.5 microg/kg of body weight/min) in halothane-anesthetized horses. ANIMALS: 6 adult Thoroughbred horses. PROCEDURE: Anesthesia was induced by use of romifidine (100 microg/kg) and ketamine (2.2 mg/kg), IV. Anesthesia was maintained by halothane (end-tidal concentration 0.9 to 1.0%). Aortic, left ventricular, and right atrial pressures were measured, using catheter-mounted strain gauge transducers. Cardiac output (CO), velocity time integral, maximal aortic blood flow velocity and acceleration, and left ventricular preejection period and ejection time were measured from aortic velocity waveforms obtained by transesophageal Doppler echocardiography. Velocity waveforms were recorded from the femoral vessels, using Doppler ultrasonography. The time-averaged mean velocity and early diastolic deceleration slope (EDDS) were measured. Pulsatility index (PI) and volumetric flow were calculated. Microvascular perfusion was measured in the semimembranosus muscles by laser Doppler flowmetry. Data were recorded 60 minutes after induction of anesthesia (control) and at 15 and 30 minutes after start of an infusion of dobutamine (0.5 microg/kg/min). RESULTS: Aortic pressures were significantly increased during the infusion of dobutamine. No change was observed in the indices of left ventricular systolic function including CO. Femoral arterial flow significantly increased, and the PI and EDDS decreased. No change was observed in the femoral venous flow or in microvascular perfusion. CONCLUSIONS AND CLINICAL RELEVANCE: At this dosage, dobutamine did not alter left ventricular systolic function. Femoral blood flow was preferentially increased as the result of local vasodilatation. The lack of effect of dobutamine on microvascular perfusion suggests that increased femoral flow is not necessarily associated with improved perfusion of skeletal muscles.

Adrenergic beta-Agonists↗

PubMed2000

Repeatability of Doppler ultrasound measurements of hindlimb blood flow in halothane anaesthetised horses.

The purpose of this study was to determine the repeatability of femoral blood flow recorded using Doppler ultrasound in anaesthetised horses. Doppler ultrasound of the femoral artery and vein was performed in 6 horses anaesthetised with halothane and positioned in left lateral recumbency. Velocity spectra, recorded using low pulse repetition frequency, were used to calculate time-averaged mean velocity (TAV), velocity of component a (TaVa), velocity of component b (TaVb), volumetric flow, early diastolic deceleration slope (EDDS) and pulsatility index (PI). Within-patient variability was determined for sequential Doppler measurements recorded during a single standardised anaesthetic episode. Within-patient variability was also determined for Doppler and cardiovascular measurements recorded during 4 separate standardised anaesthetic episodes performed at intervals of at least one month. Within-patient variation during a single anaesthetic episode was small. Coefficients of variation (cv) were <12.5% for arterial measurements and <17% for venous measurements. Intraclass correlation coefficient was >0.75 for all measurements. No significant change was observed in measurements of cardiovascular function suggesting that within-patient variation observed during a single anaesthetic episode was due to measurement error. In contrast, within-patient variation during 4 separate anaesthetic episodes was marked (cv>17%) for most Doppler measurements obtained from arteries and veins. Variation in measurements of cardiovascular function were marked (cv>20%), suggesting that there is marked biological variation in central and peripheral observed. Further studies are warranted to determine the ability of this technique to detect differences in blood flow during administration of different anaesthetic agents.

Anesthetics, Inhalation↗

PubMed2000

Variability of Doppler ultrasound measurements of hindlimb blood flow in conscious horses.

Ultrasonography of the left and right femoral artery and vein was performed in 5 conscious horses. Velocity waveforms, recorded using low pulse repetition frequency, were used to calculate time-averaged mean velocity (TAV), velocity of component a (TaVa), velocity of component b (TaVb) and volumetric flow. Waveform analysis included calculation of early diastolic deceleration slope (EDDS) and pulsatility index (PI) and subjective description of the waveform. Measurements were recorded at monthly intervals for 6 months. The repeated measurements were used to determine the within-horse variation. Horses were then anaesthetised with halothane and the same measurements recorded 60 min after induction. Differences between measurements recorded in conscious and anaesthetised horses were determined. Within-horse variability for diameters of femoral arteries and veins was small (CV<10%). Within variability for all other measurements was marked (CV>11%), with within-horse variability being the largest for femoral venous flow (CV>35%). Source of variability was measurement error and biological variation. Despite variability in conscious horses it was possible to detect changes in blood flow during anaesthesia. In the femoral arteries, volumetric flow was lower and EDDS and PI was higher in anaesthetised horses. In the femoral veins, volumetric flow was also lower in anaesthetised horses. Therefore Doppler ultrasound appears to be a useful technique for studying blood flow in conscious and anaesthetised horses.

Animals↗

PubMed2000

Chronic viral hepatitis.

Both hepatitis B and hepatitis C are spread parenterally. Chronic hepatitis C is fast becoming the leading indication for liver transplantation. Most infected patients go on to develop chronic hepatitis, with approximately 20% developing liver cirrhosis or hepatocellular carcinoma after 20 years. Standard treatment now is with a combination of alpha-interferon and ribavirin, which is successful in up to 40% of patients. A vaccine is still a remote possibility and prevention remains all-important. Despite having a successful vaccine, chronic hepatitis B remains an important cause of liver cirrhosis and hepatocellular carcinoma. Treatments for active hepatitis include alpha-interferon and the newer nucleoside analogues such as lamivudine and adefovir. In patients undergoing liver transplantation, recurrence of hepatitis B in the graft can be reduced with a combination of hepatitis B immunoglobulin and these nucleoside analogues.

Antiviral Agents↗

PubMed2000

Impact of human immunodeficiency virus type-1-associated cognitive dysfunction on activities of daily living and quality of life.

We examined the impact of neuropsychological (NP) impairment on activities of daily living (ADLs) and quality of life in human immunodeficiency virus type-1 (HIV-1)-infected persons of low socioeconomic status (SES). Thirty-nine patients were stratified into one of three groups: cognitively normal (n = 13), mild cognitive impairment (n = 15), and moderate/severe impairment (n = 11). Quality of life was assessed with the Sickness Impact Profile and ADLs were evaluated via structured interview performed in the patient's residence. While there were no significant differences across groups on disease stage, drug use, depression, or estimated premorbid IQ, cognitively impaired patients were more likely to be unemployed and fail social planning and medication management tasks. Our study confirms a previously reported association between NP impairment and unemployment among HIV-1-infected patients. The data also extend this relationship to a low-SES sample with a high base rate of unemployment, and to instrumental activities of daily living other than work.

Journal Article↗

PubMed2000

The efficacy of the rapid form cervical vacuum immobilizer in cervical spine immobilization of the equipped football player.

OBJECTIVE: To determine the effectiveness of the Rapid Form Cervical Vacuum Immobilizer in controlling the cervical spine movements of a football player wearing shoulder pads and a helmet. DESIGN AND SETTING: We used a 1-group, repeated-measures experimental design to radiographically assess cervical spine range of motion with and without the Rapid Form Cervical Vacuum Immobilizer. Two experimental conditions (with and without vacuum splint) were applied to 10 subjects in a repeated-measures design. Each subject was radiographed in cervical forward flexion, extension, and lateral flexion under each experimental condition. SUBJECTS: Ten healthy male subjects without a history of cervical spine pathology or abnormality volunteered for this study. MEASUREMENTS: Cervical forward flexion, extension, and lateral flexion range of motion were compared under both treatment conditions. Joint angles were determined by straightedge tangential lines drawn on the radiographs along the foramen magnum, inferior ring border of the atlas, and along the inferior tips of the 2nd through 7th vertebral bodies. The total range of motion was determined and compared with the treatment condition by multiple paired t tests. RESULTS: The Cervical Vacuum Immobilizer limited cervical spine range of motion in forward flexion, extension, and lateral flexion. The secondary statistical analysis for the effect size determined that each group had a large effect size, indicating that the power of the experimental or vacuum splint group was high. CONCLUSIONS: We found that the Cervical Vacuum Immobilizer limited cervical spine range of motion in forward flexion, extension, and lateral flexion. The Cervical Vacuum Immobilizer can be easily placed on an injured, fully equipped football player and serves to limit cervical spine range of motion while the athlete is immobilized and transported. Future research should determine how the Cervical Vacuum Immobilizer limits range of motion with the athlete immobilized to the spine board.

Journal Article↗

PubMed1999

FLICE-inhibitory protein expression during macrophage differentiation confers resistance to fas-mediated apoptosis.

Macrophages differentiated from circulating peripheral blood monocytes are essential for host immune responses and have been implicated in the pathogenesis of rheumatoid arthritis and atherosclerosis. In contrast to monocytes, macrophages are resistant to Fas-induced cell death by an unknown mechanism. FLICE (Fas-associated death domain-like interleukin 1beta-converting enzyme)-inhibitory protein (Flip), a naturally occurring caspase-inhibitory protein that lacks the critical cysteine domain necessary for catalytic activity, is a negative regulator of Fas-induced apoptosis. Here, we show that monocyte differentiation into macrophages was associated with upregulation of Flip and a decrease in Fas-mediated apoptosis. Overexpression of Flip protected monocytes from Fas-mediated apoptosis, whereas acute Flip inhibition in macrophages induced apoptosis. Addition of an antagonistic Fas ligand antibody to Flip antisense-treated macrophages rescued cultures from apoptosis, demonstrating that endogenous Flip blocked Fas-induced cell death. Thus, the expression of Flip in macrophages conferred resistance to Fas-mediated apoptosis, which may contribute to the development of inflammatory disease.

Apoptosis↗

PubMed1999

Cyclosporine downregulates Fas ligand expression on vascular endothelial cells: implication for accelerated vasculopathy by immunosuppressive therapy.

Although the introduction of cyclosporine A (CyA) and FK506 for immunosuppressive therapy has dramatically enhanced the early survival of organ transplant recipients, administration of these immunosuppresants is correlated with high incidence of transplant arteriosclerosis. Transplant-associated arteriosclerosis is believed to result from recipient inflammatory responses to the allograft, as it is characterized by early mononuclear cell infiltration of the transplanted vessel. We reported that vascular endothelial cells naturally express a death factor, Fas ligand, that may function to inhibit detrimental leukocyte infiltration. Here, we show that CyA or FK506 downregulates FasL expression on endothelial cells with accompanying decrease in the cytotoxicity toward Fas-bearing cells. Our findings not only demonstrate a novel biological action of these drugs, but also suggest a mechanism by which immunosupressive treatment contributes to atherogenesis.

Arteriosclerosis↗

PubMed1999

A 1.3-kb upstream 5' region of the rat phosphoglycerate mutase m gene confers testis and skeletal muscle-specific expression in transgenic mice.

Spermatogenesis is a complex process that occurs in successive mitotic, meiotic and post-meiotic phases and involves a highly regulated selective gene-expression pattern. However, this process has not been well characterised at the gene expression level due to the absence of germinal cell lines. We previously demonstrated that the rat skeletal muscle-specific gene for the glycolytic enzyme phosphoglycerate mutase is also specifically expressed in meiotic and haploid male germ cells from testis (12). To analyse the promoter elements that regulate the transcription of the phosphoglycerate mutase m gene (pgam-m)during spermatogenesis, we developed transgenic mice for a construct containing 1.3 kb from the pgam-m promoter linked to the Escherichia coli LacZ gene. RNA analysis by retrotranscription and PCR amplification of transgene expression showed transcriptional activity in the testis with a pattern during testis development that was identical to the endogenous gene. The transgene was also active in skeletal muscle but not in the adult heart in all the transgenic lines analysed. Collectively, these studies demonstrate that the 1.3 kb pgam-m promoter contains sufficient sequences to specify temporally regulated testis-specific expression as well as skeletal-muscle expression.

Animals↗

PubMed1999

A recombinant defective adenoviral agent expressing anti-bcl-2 ribozyme promotes apoptosis of bcl-2-expressing human prostate cancer cells.

Over-expression of bcl-2, a potent anti-apoptosis protein, is likely to be one of the genetic mechanisms through which human prostate cancer cells develop resistance to hormonal and other forms of therapy. To develop a therapeutic agent for hormone-resistant prostate cancer based on suppression of bcl-2 expression, we had previously designed and synthesized a dual-hammerhead ribozyme capable of recognizing and specifically cleaving human bcl-2 mRNA in vitro as well as in vivo. To increase the efficiency by which the anti-bcl-2 ribozyme can be delivered to target cells, we have created a recombinant replication-deficient (defective) adenoviral agent capable of expressing the anti-bcl-2 ribozyme upon infection. This viral agent effectively reduces intracellular levels of bcl-2 mRNA and protein in cultured LNCaP prostate cancer cells following standard infection procedures. Likewise, the defective adenovirus-anti-bcl-2 ribozyme induces extensive apoptosis in several androgen-sensitive (LNCaP) and androgen-insensitive (LNCaP/bcl-2 and PC-3) human prostate cancer cell lines that express differing amounts of bcl-2 protein. One androgen-insensitive prostate cancer cell line, DU-145, lacking in bcl-2 expression, was found to be completely refractory to the effects of the virus ribozyme, supporting the concept that the cytotoxic effects of the ribozyme are based solely on its effects on bcl-2 expression. Our results support further development of this adenovirus/anti-bcl-2 ribozyme for potential gene therapeutic purposes in certain forms of hormone-resistant prostate cancer where over-expression of bcl-2 proto-oncogene is indicated.

Adenoviruses, Human↗

PubMed1999

Reactive oxygen species mediate the activation of Akt/protein kinase B by angiotensin II in vascular smooth muscle cells.

Angiotensin II, a hypertrophic/anti-apoptotic hormone, utilizes reactive oxygen species (ROS) as growth-related signaling molecules in vascular smooth muscle cells (VSMCs). Recently, the cell survival protein kinase Akt/protein kinase B (PKB) was proposed to be involved in protein synthesis. Here we show that angiotensin II causes rapid phosphorylation of Akt/PKB (6- +/- 0.4-fold increase). Exogenous H(2)O(2) (50-200 microM) also stimulates Akt/PKB phosphorylation (maximal 8- +/- 0.2-fold increase), suggesting that Akt/PKB activation is redox-sensitive. Both angiotensin II and H(2)O(2) stimulation of Akt/PKB are abrogated by the phosphatidylinositol 3-kinase (PI3-K) inhibitors wortmannin and LY294002 (2(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one), suggesting that PI3-K is an upstream mediator of Akt/PKB activation in VSMCs. Furthermore, diphenylene iodonium, an inhibitor of flavin-containing oxidases, or overexpression of catalase to block angiotensin II-induced intracellular H(2)O(2) production significantly inhibits angiotensin II-induced Akt/PKB phosphorylation, indicating a role for ROS in agonist-induced Akt/PKB activation. In VSMCs infected with dominant-negative Akt/PKB, angiotensin II-stimulated [(3)H]leucine incorporation is attenuated. Thus, our studies indicate that Akt/PKB is part of the remarkable spectrum of angiotensin II signaling pathways and provide insight into the highly organized signaling mechanisms coordinated by ROS, which mediate the hypertrophic response to angiotensin II in VSMCs.

Angiotensin II↗

PubMed1999

Regulation of endothelium-derived nitric oxide production by the protein kinase Akt.

Endothelial nitric oxide synthase (eNOS) is the nitric oxide synthase isoform responsible for maintaining systemic blood pressure, vascular remodelling and angiogenesis. eNOS is phosphorylated in response to various forms of cellular stimulation, but the role of phosphorylation in the regulation of nitric oxide (NO) production and the kinase(s) responsible are not known. Here we show that the serine/threonine protein kinase Akt (protein kinase B) can directly phosphorylate eNOS on serine 1179 and activate the enzyme, leading to NO production, whereas mutant eNOS (S1179A) is resistant to phosphorylation and activation by Akt. Moreover, using adenovirus-mediated gene transfer, activated Akt increases basal NO release from endothelial cells, and activation-deficient Akt attenuates NO production stimulated by vascular endothelial growth factor. Thus, eNOS is a newly described Akt substrate linking signal transduction by Akt to the release of the gaseous second messenger NO.

Animals↗

PubMed1999

Akt mediates cytoprotection of endothelial cells by vascular endothelial growth factor in an anchorage-dependent manner.

Regulation of endothelial cell apoptosis is a critical modulator of normal and pathological angiogenesis. In this study, we examined the role of the protein kinase Akt/PKB in endothelial cell survival in response to growth factor and matrix attachment signals. Vascular endothelial growth factor(VEGF)-induced cytoprotection of endothelial cell monolayers correlated with the wortmannin-sensitive induction of Akt activity. Transfection of an adenovirus expressing a dominant-negative Akt mutant decreased endothelial cell viability in the presence of VEGF. Conversely, adenoviral transduction of wild-type Akt facilitated the cell survival effects of VEGF, whereas transduction of constitutively active Akt conferred endothelial cell survival in the absence of VEGF. Constitutively active Akt also conferred survival to endothelial cells in suspension culture, whereas stimulation with VEGF did not. In suspension cultures, VEGF stimulation was unable to activate Akt, and Akt protein levels were repressed in cells undergoing anoikis. These data suggest that cross-talk between growth factor- and anchorage-dependent signaling pathways are essential for Akt activation and endothelial cell survival.

Androstadienes↗

PubMed1999

Adenovirus-mediated delivery of fas ligand inhibits intimal hyperplasia after balloon injury in immunologically primed animals.

BACKGROUND: Adenoviral constructs have been used for studies of injury-induced vascular hyperplasia in immunologically naive laboratory animals, but their usefulness for intra-arterial gene therapy may be limited by the prevalence of preexisting immunity to adenovirus in the patient population. Here, we explored the efficacy of adenovirus-mediated transfer of Fas ligand, a cytotoxic gene with immunomodulatory properties, in inhibiting injury-induced vascular lesion formation in both naive and immunologically primed animals. METHODS AND RESULTS: Lesion formation was evaluated in balloon-injured carotid arteries of naive and adenovirus-immunized rats that were infected with adenoviral constructs expressing Fas ligand (Ad-FasL), the cyclin-dependent kinase inhibitor p21 (Ad-p21), or beta-galactosidase (Ad-betagal). In naive rats, Ad-FasL induced apoptosis in medial vascular smooth muscle cells and inhibited intimal hyperplasia by 60% relative to Ad-betagal-treated vessels (P<0.05), whereas the cytostatic agent Ad-p21 decreased lesion size by 58% (P<0.05). In animals preimmunized with an adenoviral vector containing no transgene, Ad-FasL significantly inhibited neointima formation (73% reduction, P<0.05), but Ad-p21 failed to inhibit neointima formation relative to controls. Immunologically primed rats displayed robust T-cell infiltration in Ad-p21- and Ad-betagal-treated vessels, but T-cell infiltration was markedly attenuated in Ad-FasL-treated vessels. CONCLUSIONS: Our data demonstrate that adenovirus-mediated Fas ligand delivery can inhibit intimal hyperplasia in both immunologically primed and naive animals, whereas the efficacy of an adenovirus-mediated p21 delivery is limited to immunologically naive animals. This study documents, for the first time, the therapeutic efficacy of intravascular adenoviral gene transfer in animals with preexisting immunity to adenovirus.

Adenoviridae↗

PubMed1999

Reversal of GATA-6 downregulation promotes smooth muscle differentiation and inhibits intimal hyperplasia in balloon-injured rat carotid artery.

The GATA-6 transcription factor is expressed in quiescent vascular smooth muscle cells (VSMCs) in culture, and levels of its transcript are rapidly downregulated on mitogen stimulation. In this study, we demonstrate that the GATA-6 transcript, protein, and DNA-binding activity are downregulated in rat carotid arteries on balloon injury. Downregulation was detected at 1 and 3 days after injury and recovered by 7 days. To assess the role of GATA-6 downregulation in injury-induced vascular lesion formation, adenoviral vectors were used to express wild-type human GATA-6 cDNA (Ad-GATA6) or an inactive mutant cDNA that lacks a portion of the zinc-finger domain (Ad-GATA6DeltaZF). Adenovirus-mediated GATA-6 gene transfer to the vessel wall after balloon injury partially restored the levels of GATA-6 protein and DNA-binding activity to before injury levels. The local delivery of Ad-GATA6 but not Ad-GATA6DeltaZF inhibited lesion formation by 46% relative to saline control and 50% relative to a control adenovirus that expressed lacZ. Local delivery of Ad-GATA6 also reversed changes in the expression patterns of smooth muscle myosin heavy chain, smooth muscle alpha-actin, calponin, vinculin, metavinculin, and proliferating cell nuclear antigen that are associated with injury-induced VSMC phenotypic modulation. These data indicate that the injury-induced downregulation of GATA-6 is an essential feature of VSMC phenotypic modulation that contributes to vessel lesion formation.

Adenoviridae↗

PubMed1999

Early cell loss after angioplasty results in a disproportionate decrease in percutaneous gene transfer to the vessel wall.

Acute cell loss has been documented following angioplasty of normal rat and rabbit arteries. Here we analyzed the effects of balloon injury intensity on early cellular loss in single- and double-injury models and how it influences the efficiency of percutaneous gene delivery to the vessel wall. Rabbits underwent bilateral iliac angioplasties (n = 52) with 2.5-mm (balloon-to-artery [B/A] ratio, 1.08 to 1.13) and 3.0-mm (B/A ratio, 1.29 to 1.34) balloons. In the single-injury model, the 3.0-mm balloon induced a 61% reduction in medial cellularity at 3 days postinjury (p < 0.001) while the 2.5-mm balloon did not produce significant cell loss. In the double-injury model, the effects were more pronounced, with 35% (p < 0.01) and 91% (p < 0.001) reductions in medial cellularity at 3 days with the 2.5- and 3.0-mm balloons, respectively, but neointimal cellularity was decreased only with the 3.0-mm balloon (37% reduction, p = 0.025). Adenovirus-mediated beta-galactosidase gene delivery with a channel balloon (n = 24) revealed that larger balloon-to-artery ratios decreased both absolute levels and relative frequencies of transgene expression in the vessel wall. In the single-injury model, gene transfer efficiency was 4.2+/-1.1 and 1.3+/-0.25% (p < 0.05) for the small and large balloons, respectively. In the double-injury model, gene transfer efficiency was 6.6+/-1.6 and 2.3+/-0.8% (p < 0.05) in the neointima and 4.1+/-1.2 and 2.6+/-1.2% (p = NS) in the media for the small and large balloon, respectively. We conclude that early cell loss is dependent on the intensity of the injury in both single- and double-injury models of balloon angioplasty, with greater frequencies of cell loss occurring in the media than in the neointima. In both models, larger balloon-to-artery ratios result in disproportionate reductions in percutaneous adenovirus-mediated gene delivery.

Adenoviridae↗