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Biomedical subjects

M Osako

Publications and source records attributed to M Osako.

At least 19 recordsLinked to original sources
PubMed2005

MUC4 expression is a novel prognostic factor in patients with invasive ductal carcinoma of the pancreas.

BACKGROUND: Many patients with invasive ductal carcinoma of the pancreas (IDC) have a poor outcome. MUC4 expression has been implicated as a marker for diagnosis and progression of IDC, but there are no studies of the relation between MUC4 expression and patient prognosis in IDC. AIMS: To investigate the prognostic significance of MUC4 expression in IDC. METHODS: The expression profiles of MUC4, ErbB2, p27, and MUC1 were investigated in IDC tissues from 135 patients by means of immunohistochemistry. RESULTS: MUC4 was expressed in 43 of the 135 patients with IDC (31.9%). The survival of 21 patients with high MUC4 expression (>20% of neoplastic cells stained) was significantly worse than that of the 114 patients with low MUC4 expression (<20% of neoplastic cells stained) (p = 0.0043). Univariate analysis showed that high MUC4 expression (p = 0.0061), large primary tumour status (>T2) (p = 0.0436), distant metastasis (p = 0.0383), lymphatic invasion (p = 0.0243), and surgical margins (p = 0.0333) were significant risk factors affecting the outcome of patients with IDC. Backward stepwise multivariate analysis showed that MUC4 expression (p = 0.0121), lymph node metastasis (p = 0.0245), and lymphatic invasion (p = 0.0239) were significant independent risk factors. ErbB2, p27, and MUC1 were not independent risk factors. CONCLUSIONS: This study shows that MUC4 expression in IDC is a new independent factor for poor prognosis and predicts the outcome of patients with IDC.

Adult↗
PubMed2004

Effect of adsorption capacity of dissolved humic matter on leachability of dioxins from raw and treated fly ashes of municipal solid waste incinerators.

The purposes of this study are to obtain information on the leachability of dioxins depending on the samples, to confirm the effect of dissolved humic matter (DHM) on the leachability of dioxins, and to evaluate the suitability of the detoxification treatments specified by the Japanese government for the reduction of leachability of dioxins. In this study, the leachability of dioxins from raw and treated fly ash was evaluated by a 24-hour batch leaching test and by an extraction test repeated three times with DHM solution, whose concentration was determined to be 700 mg-OC/L as an initial concentration based on organic carbon (OC) from adsorption tests of DHM to fly ash. The leaching concentration from fly ash samples having high DHM adsorption capacity was low regardless of pH, and that from samples having relatively low adsorption capacity and high pH was largely increased. Therefore, it is expected that the leachability of dioxins from treated fly ashes would be reduced by avoiding high pH and enhancing the DHM adsorption capacity rather than by using the detoxification method specified. We also confirmed that increase of the leachability of HOPs due to DHM is not as large as known in condition that is composed of three phases of HOPs, DHM, and solid matrix.

Adsorption↗
PubMed2002

Long-term results of chronic hemodialysis patients with isolated coronary artery bypass grafting performed by the same surgeon. A comparative study.

BACKGROUND: The aim of this study was to examine the long-term results of isolated coronary artery bypass grafting (CABG) patients who required chronic hemodialysis. METHODS: From May 1990 to June 2000, 23 hemodialysis patients received isolated CABG performed by the same surgeon. Postoperative follow-up was completed with maximum duration of 122 months. RESULTS: Operative deaths (n=2) were due to acute circulatory failure related to hemodialysis. The most frequent cause of late deaths (n=10) was infection. Five (50%) patients died of sepsis, and 80% of sepsis was caused by leg infection associated with arteriosclerosis obliterans. There were 6 late cardiac events including 3 cardiac deaths. The actual survival rates 1, 3, 5 and 7 years after CABG were 68.6%, 42.5%, 35.4% and 35.4%, respectively. And the actual cardiac event free rates 1, 3, 5 and 7 years after CABG were 77.6%, 77.6%, 46.6% and 46.6%, respectively. Operative mortality (p=0.019), long-term survival (p<0.001) and cardiac event free rate (p=0.002) were significantly poorer in hemodialysis patients than in non-hemodialysis patients. However, the long-term survival rate of our hemodialysis patients receiving isolated CABG was almost similar to that in dialysis patients without CABG. The etiology of chronic renal failure did not significantly affect long-term RESULTS. Using internal thoracic artery graft significantly (p=0.02) decreased the late cardiac event in hemodialysis patients, although it did not improve late survival. CONCLUSIONS: Primary CABG followed by aggressive re-intervention have the benefit of preventing late cardiac death in hemodialysis patients. However, prevention of sepsis and treatment of arteriosclerosis obliterans are important for improving the late survival in hemodialysis patients receiving isolated CABG.

Aged↗
PubMed2001

Experimental study of pulmonary artery infusion with cisplatin in a solitary pulmonary tumor model using a rat colorectal adenocarcinoma cell line.

OBJECTIVES: We assessed a tumor model prepared by open lung injection to study metastatic lung tumors, and evaluated the efficacy of pulmonary artery infusion. METHODS: Subjects were 30 male F344 rats. In experiment 1, we evaluated chemosensitivity of a rat colorectal adenocarcinoma cell line (RCN-9) using a colorimetric [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. In experiment 2, we injected RCN-9 cells into the left lung on day 0; on day 10, we measured tumor tissue blood flow before and after pulmonary arterial occlusion. In experiment 3, we injected RCN-9 cells into the left lung and conducted no further procedures in controls. The pulmonary artery infusion group underwent pulmonary artery infusion with 0.1 mg of cisplatin on day 3 and the sham group injection with saline solution alone. On day 10, rats were sacrificed and maximum tumor cross-section measured. RESULTS: In experiment 1, the drug concentration required to inhibit cell growth 50% was 2.45 x 10(-6) M. In experiment 2, tumor tissue blood flow decreased significantly after arterial occlusion (p = 0.003). In experiment 3, the maximum tumor cross-section in the pulmonary artery infusion group was significantly smaller than in shams (p = 0.0027) and controls (p = 0.0019). CONCLUSIONS: The pulmonary artery supplies tumors with blood, so this model appears useful in studying metastatic lung tumors, whose size was reduced significantly by pulmonary artery infusion with cisplatin. Pulmonary artery infusion is thus a promising modality in metastatic lung tumor treatment.

Adenocarcinoma↗
PubMed2001

Protein kinase C isoform-dependent myocardial protection by ischemic preconditioning and potassium cardioplegia.

OBJECTIVE: Ischemic preconditioning combined with potassium cardioplegia does not always confer additive myocardial protection. This study tested the hypothesis that the efficacy of ischemic preconditioning under potassium cardioplegia is dependent on protein kinase C isoform. METHODS: Isolated and crystalloid-perfused rat hearts underwent 5 cycles of 1 minute of ischemia and 5 minutes of reperfusion (low-grade ischemic preconditioning) or 3 cycles of 5 minutes of ischemia and 5 minutes of reperfusion (high-grade ischemic preconditioning) or time-matched continuous perfusion. These hearts received a further 5 minutes of infusion of normal buffer or oxygenated potassium cardioplegic solution. The isoform nonselective protein kinase C inhibitor chelerythrine (5 micromol/L) was administered throughout the preischemic period. All hearts underwent 35 minutes of normothermic global ischemia followed by 30 minutes of reperfusion. Isovolumic left ventricular function and creatine kinase release were measured as the end points of myocardial protection. Distribution of protein kinase C alpha, delta, and epsilon in the cytosol and the membrane fractions were analyzed by Western blotting and quantified by a densitometric assay. RESULTS: Low-grade ischemic preconditioning was almost as beneficial as potassium cardioplegia in improving functional recovery; left ventricular developed pressure 30 minutes after reperfusion was 70 +/- 15 mm Hg (P <.01) in low-grade ischemic preconditioning and 77 +/- 14 mm Hg (P <.001) in potassium cardioplegia compared with values found in unprotected control hearts (39 +/- 12 mm Hg). Creatine kinase release during reperfusion was also equally inhibited by low-grade ischemic preconditioning (18.2 +/- 10.6 IU/g dry weight, P <.05) and potassium cardioplegia (17.6 +/- 6.7 IU/g, P <.01) compared with control values. However, low-grade ischemic preconditioning in combination with potassium cardioplegia conferred no significant additional myocardial protection; left ventricular developed pressure was 80 +/- 17 mm Hg, and creatine kinase release was 14.8 +/- 11.0 IU/g. In contrast, high-grade ischemic preconditioning with potassium cardioplegia conferred better myocardial protection than potassium cardioplegia alone; left ventricular developed pressure was 121 +/- 16 mm Hg (P <.001), and creatine kinase release was 8.3 +/- 5.8 IU/g (P <.05). Chelerythrine itself had no significant effect on functional recovery and creatine kinase release in the control hearts, but it did inhibit the salutary effects not only of low-grade and high-grade ischemic preconditioning but also those of potassium cardioplegia. Low-grade ischemic preconditioning and potassium cardioplegia enhanced translocation of protein kinase C alpha to the membrane, whereas high-grade ischemic preconditioning also enhanced translocation of protein kinase C delta and epsilon. Chelerythrine inhibited translocation of all 3 protein kinase C isoforms. CONCLUSIONS: These results suggest that myocardial protection by low-grade ischemic preconditioning and potassium cardioplegia are mediated through enhanced translocation of protein kinase C alpha to the membrane. It is therefore suggested that activation of the novel protein kinase C isoforms is necessary to potentiate myocardial protection under potassium cardioplegia.

Animals↗
PubMed2001

Insulin-like growth factor 1 prevents neuronal cell death and paraplegia in the rabbit model of spinal cord ischemia.

OBJECTIVE: Insulin-like growth factor 1 has been shown to be cytoprotective against ischemia-reperfusion injury in various organs. However, spinal cord protection by insulin-like growth factor 1 has not been tested. We have therefore examined the effect of insulin-like growth factor 1 on neuronal cell death and motor function after spinal cord ischemia. METHODS: Japanese white rabbits were subjected to spinal cord ischemia by clamping the abdominal aorta for 15 minutes. Insulin-like growth factor 1 (0.3 mg/kg) at a dose equipotent to insulin (0.3 IU/kg) in lowering blood glucose level or the control (phosphate-buffered saline solution as a vehicle) was administered intravenously 30 minutes before the aortic clamp. RESULTS: Hind-limb motor function had recovered normally 48 hours after the operation in all the rabbits (n = 8) treated with insulin-like growth factor 1. In contrast, all the control-treated (n = 8) and all but one of the insulin-treated (n = 6) rabbits had deteriorated to paraplegia by 48 hours after the operation. Histopathologic sections in the involved spinal cord segment showed that a significantly (P <.0001) greater number of motor neuron cells were preserved in the rabbits treated with insulin-like growth factor 1 (17.9 +/- 4.8 per section) than in those treated with the control (8.0 +/- 2.1). Although insulin was equipotent to insulin-like growth factor 1 in preserving the number of motor neuron cells (18.5 +/- 2.7), the percentage of motor neuron cells positive for terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate-biotin nick-end labeling were significantly (P <.01) smaller in the rabbits treated with insulin-like growth factor 1 (6.0 +/- 4.6) compared with those treated with the control (54.6 +/- 33.8) and insulin (26.2 +/- 11.7). Immunohistochemical studies revealed that insulin-like growth factor 1 increased expression of the antiapoptotic Bcl-xL protein and inhibited expression of the proapoptotic Bax protein in motor neuron cells 24 and 48 hours after the operation. In contrast, expression of only Bax was increased after the operation in other groups of rabbits subjected to spinal cord ischemia. CONCLUSIONS: These results suggest that insulin-like growth factor 1, but not insulin with a conventional dose, protects motor neuron cells from ischemic spinal cord injury associated with differential regulation of Bcl-xL and Bax protein.

Animals↗
PubMed2001

Dual involvement of coenzyme Q10 in redox signaling and inhibition of death signaling in the rat heart mitochondria.

Coenzyme Q10 (CoQ) has long been utilized as a cardioprotective agent in various heart diseases. One of the most important mechanisms by which CoQ exerts cardioprotection is aerobic ATP production as a mobile electron carrier in the mitochondrial electron transfer chain. The ability of CoQ to afford myocardial protection is also attributed to its antioxidant property. However, CoQ may also act as a pro-oxidant through the generation of reactive oxygen species. Although excess oxidative stress is known to induce death signaling via cytochrome c release from mitochondria, it is now apparent that a brief exposure to oxidative stress stimulates redox signaling for acquisition of tolerance to oxidative stress. Therefore, we have investigated dual involvement of CoQ in redox signaling generation through enhanced production of reactive oxygen species and death signaling inhibition through antioxidation. Mitochondria were isolated from the rat heart and incubated with CoQ (10 or 100 microM) or its vehicle HCO 60 for 1 h. H2O2 and cytochrome c release from respiring mitochondria were increased by antimycin A (2 microM), an inhibitor of complex III respiratory chain, or by high Ca2+ (10 microM). This enhanced release of H2O2 was associated with an increase in lipid peroxidation as measured with 4-hydroxy-2-nonenal-modified proteins and with large amplitude swelling of mitochondria. CoQ potentiated H2O2 release from antimycin A- or high Ca(2+)-treated mitochondria, but was capable of inhibiting lipid peroxidation and large amplitude swelling, and attenuated cytochrome c release from the mitochondria. In addition, CoQ increased ATP synthesis by mitochondria. These results suggest that CoQ plays dual roles in mitochondrial generation of intracellular signaling. CoQ acts as a pro-oxidant that participates in redox signaling. CoQ also acts as an antioxidant that inhibits permeability transition and cytochrome c release, and increases ATP synthesis, thereby attenuating death signaling toward apoptosis and necrosis.

Adenosine Triphosphate↗
PubMed2001

IGF-I differentially regulates Bcl-xL and Bax and confers myocardial protection in the rat heart.

Bcl-2 family proteins play a crucial role in the cytoprotective action of insulin-like growth factor-I (IGF-I) by regulating cell death signaling at the mitochondrial level. The present study examined the effect of IGF-I on the expression of Bcl-2 family proteins in the rat heart mitochondria in relation to myocardial protection against ischemia-reperfusion injury. Systemic IGF-I (1 mg) treatment in the rat increased Bcl-xL and attenuated Bax 12-24 h later in the heart mitochondria fraction. Permeability transition and cytochrome c release occurred in a Ca(2+) concentration-dependent manner in the vehicle-treated mitochondria. This was significantly inhibited by the IGF-I-pretreatment. Moreover, ATP synthesis was significantly greater in the IGF-I-pretreated mitochondria. IGF-I pretreatment 24 h before 25 min of global ischemia in the isolated rat heart model significantly improved recovery of isovolumic left ventricular function and inhibited creatine kinase release during reperfusion. This was associated with a significantly less number of terminal transferase labeling-positive myocytes and nonmyocytes 2 h after reperfusion. These results suggest that IGF-1 differentially regulates Bcl-xL and Bax in heart mitochondria, which may be causally related to myocardial protection against ischemia-reperfusion injury.

Adenosine Triphosphate↗
PubMed2001

NHE and ICAM-1 expression in hypoxic/reoxygenated coronary microvascular endothelial cells.

Although Na+/H+ exchange (NHE) has been implicated in myocardial reperfusion injury, participation of coronary microvascular endothelial cells (CMECs) in this pathogenesis has been poorly understood. NHE-induced intracellular Ca2+ concentration ([Ca2+]i) overload in CMECs may increase the synthesis of intercellular adhesion molecules (ICAM), which is potentially involved in myocardial reperfusion injury. The present study tested the hypothesis that NHE plays a crucial role in [Ca2+]i overload and ICAM-1 synthesis in CMECs. Primary cultures of CMECs isolated from adult rat hearts were subjected to acidic hypoxia for 30 min followed by reoxygenation. Two structurally distinct NHE inhibitors, cariporide and 5-(N-N-dimethyl)-amiloride (DMA), had no significant effect on the acidic hypoxia-induced decrease in intracellular pH (pH(i)) of CMECs but significantly retarded pH(i) recovery after reoxygenation. These NHE inhibitors abolished the hypoxia- and reoxygenation-induced increase in [Ca2+]i. Expression of ICAM-1 mRNA was markedly increased in the vehicle-treated CMECs 3 h after reoxygenation, and this was significantly inhibited by treatment with cariporide, DMA, or Ca2+-free buffer. In addition, enhanced ICAM-I protein expression on the cell surface of CMECs 8 h after reoxygenation was attenuated by treatment with cariporide, DMA, or Ca2+-free buffer. These results suggest that NHE plays a crucial role in the rise of [Ca2+]i and ICAM-1 expression during acidic hypoxia/reoxygenation in CMECs. We propose that inhibition of ICAM-1 expression in CMECs may represent a novel mechanism of action of NHE inhibitors against ischemia-reperfusion injury.

Amiloride↗
PubMed2001

Patch repair of postinfarction pseudo- and subepicardial aneurysm of the left ventricle.

Left ventricular pseudo-aneurysm and subepicardial aneurysm are rare complications of myocardial infarction. However, the prognosis of medical treatment is extremely poor and the operative procedure is controversial. We experienced 3 consecutive patients with this unusual left ventricular aneurysm, and described the clinical presentation, operative procedure and its result in these patients. The interval from myocardial infarction to discovering aneurysmal formation is short. The term was within a month. In all patients, the papillary muscle was in the proximity of the orifice of the aneurysm. Patch repair of these unusual left ventricular aneurysms may be effective for improvement of left ventricular function without mitral regurgitation.

Aged↗
PubMed2001

[Comparison of detectability of visual field abnormality by frequency doubling technology in primary open-angle glaucoma and normal-tension glaucoma].

PURPOSE: To compare the effectiveness of frequency doubling technology(FDT) in detecting abnormalities in primary open-angle glaucoma(POAG) and normal-tension glaucoma(NTG). SUBJECTS AND METHODS: Twenty-nine POAG patients (29 eyes) and 27 NTG-patients(27 eyes) were studied. All subjects underwent testing with program C-20 of FDT with appropriate corrective lenses. RESULTS: No significant differences were observed between the two groups in mean age, mean deviation(MD), and pattern standard deviation(PSD) measured by the Humphrey Field Analyzer(HFA). The correlation between MD values determined by HFA(x) and FDT(y) is represented by y = 0.60x - 2.7 (r = 0.78, p < 0.01) in the POAG group and y = 0.59x + 0.6 (r = 0.81, p < 0.001) in the NTG group. No significant difference was found in the average PSD between the two groups. In early glaucoma cases (MD > or = -5 dB by HFA), a larger proportion of cases in the POAG group than the NTG group had a lower significance level of MD determined by FDT than by HFA (p < 0.02). At many test points on the temporal periphery in FDT the mean sensitivity was lower in the POAG group than in the NTG group; whereas no significant differences among HFA test points were observed. CONCLUSIONS: FDT detected visual field abnormalities in POAG cases more sensitively than in NTG cases. This finding indicates that the pathogenesis of My-cell damage is different in POAG and NTG.

Glaucoma↗
PubMed2000

Vacuolar H(+)-ATPase plays a crucial role in growth and phenotypic modulation of myofibroblasts in cultured human saphenous vein.

BACKGROUND: The molecular mechanism of neointimal hyperplasia after vein graft surgery remains elusive. Vacuolar H(+)-ATPase (V-ATPase) is involved in intracellular trafficking and may play a crucial role in neointimal cell growth. METHODS AND RESULTS: Cultured human saphenous vein segments developed neointimal formation within 10 days. Neointimal cells were positive for vimentin and alpha-smooth muscle actin but negative for desmin, which is indicative of myofibroblasts. Those myofibroblasts were found to have originated from periadventitial fibroblasts, which upregulated the expression of 16-kDa proteolipid of V-ATPase before proliferation and phenotypic modulation. Neointimal myofibroblast growth and survival were highly sensitive to inhibition of V-ATPase by bafilomycin A(1) (BA(1)), because the incorporation of [(3)H]thymidine into the myofibroblasts was significantly inhibited by nanomolar concentrations of BA(1) and apoptotic cell death was induced by a similar concentration range of BA(1). In contrast, endothelial cells and differentiated smooth muscle cells were resistant to apoptosis by BA(1). CONCLUSIONS: These results suggest that V-ATPase plays a crucial role in growth and phenotypic modulation of myofibroblasts that contributes to neointimal formation in cultured human saphenous vein.

Adult↗
PubMed2000

Bypass graft material and myocardial protective procedure in combined coronary artery bypass grafting and valve surgery.

OBJECTIVE: The aortic cross clamping time is prone to be longer when coronary artery bypass grafting (CABG) is combined with valve surgery. Therefore, the myocardium that is revascularized by in-situ internal thoracic artery graft is at risk to ischemia, and, myocardial protection is especially important in such operation. In this study, the effect of myocardial preservation of combined antegrade, retrograde and terminal warm blood cardioplegia during combined valve surgery and CABG using the internal thoracic artery as a bypass conduit was evaluated. METHODS: From November 1992 to August 1999, 15 patients received combined CABG and valve surgery. Among these 15 patients, 13 patients who did not need hemodialysis were divided into 2 groups, and a comparative study was done. In Group I (n = 5), only the saphenous vein graft was employed for combined CABG and valve surgery, and myocardial protection was done by combined antegrade and terminal warm blood cardioplegia. In Group II (n = 8), at least 1 in-situ internal thoracic artery graft was employed for CABG and valve surgery, and myocardial protection was done by combined antegrade, retrograde and terminal warm blood cardioplegia. RESULTS: Despite longer aortic cross clamping time in Group II, the peak creatine kinase-MB of Group II was significantly lower. In addition, the postoperative administration of dopamine tended to be less in Group II. CONCLUSION: Myocardial protection by combined antegrade, retrograde and terminal warm blood cardioplegia may be an effective adjunct to combined valve surgery and CABG employing the in-situ internal thoracic artery graft.

Aged↗
PubMed2000

Freehand cryopreserved mitral valve allograft with flexible ring in the pig.

OBJECTIVE: Cryopreserved valve allografts have proven satisfactory in aortic and pulmonary positions but not mitrally because of the difficulty in properly aligning the mitral valve allograft due to the complex subvalvular apparatus. To make the surgical procedure easier, we developed a freehand cryopreserved mitral valve allograft with a flexible ring. METHODS: Whole cryopreserved mitral valve allografts with the papillary muscle, chordae, and leaflets from donor pigs were implanted mitrally in recipient pigs under cardiopulmonary bypass divided into 2 experimental groups; control allografts without the ring (n = 6) (CA group) and allografts with a flexible ring (n = 7) (RA group). Postimplantation hemodynamics and valvular function were evaluated by measuring arterial pressure, left ventricular end diastolic pressure, and left atrial pressure and by evaluating 2-dimensional echocardiography. Allografts were evaluated pathohistologically after cryopreservation and surgery by light microscopy. RESULTS: Hemodynamics did not differ significantly between groups. Aortic cross-clamping and Cardiopulmonary bypass times were significantly shorter in the RA group than the CA group (p < 0.05). Pigs requiring optional procedures with sutured annuloplasty and valvuloplasty numbered more in the CA group than the RA group. Postoperative echocardiography showed satisfactory mitral valve opening in diastole and good leaflet coaptation in systole in both groups. Light microscopic examination of cryopreserved allografts after surgery showed almost normal structures. CONCLUSIONS: Acute hemodynamic function and morphology of freehand cryopreserved valve allografts implanted mitrally in pigs proved acceptable. Adaptation of the flexible ring to allografts might be useful for technical benefit to facilitate accurate positioning of mitral subvalvular apparatus at implantation.

Animals↗
PubMed2000

Fate of fibrin sealant in pericardial space.

BACKGROUND: Although fibrin sealant (Beriplast, Aventis Behring, Marburg, Germany) has been widely used as a supplementary measure for hemostasis during cardiac surgery in Europe and is becoming popular in the United States, the pharmocokinetics of fibrin sealant applied in pericardial space has not been elucidated. METHODS: A small incision was made on the epicardial surface of the left ventricle of a rat, and the incision was sutured. Total 0.2 ml of fibrin sealant containing iodine 125 (125I)-labeled fibrinogen, aprotinin, blood coagulation factor XIII and thrombin was applied to the area around the suture line. RESULTS: Distributions of 125I-labeled fibrinogen in the heart on postoperative days 1, 3, 7, and 14 were 48.2% +/- 1.8%, 20.7% +/- 2.2%, 0.15% +/- 0.02%, and 0.01% +/- 0.02%, respectively. The radioactivity was negligible in the blood, liver, spleen, and kidney except for the thyroid in which the radioactivity increased to 7.9% +/- 0.7% and 4.3% +/- 0.4%, respectively, on postoperative days 7 and 14. Iodine 125-labeled fibrinogen concentrations of the heart and other organs showed a similar change in the time course of distribution. Dense and thick fibrin network, observed on postoperative day 1, had dissipated and was thinner with collagen formation by postoperative day 7. CONCLUSIONS: Fibrin sealant applied to the pericardial cavity regresses rapidly and plays an important role in wound healing.

Animals↗
PubMed2000

Potential role of vacuolar H-adenosine triphosphatase in neointimal formation in cultured human saphenous vein.

OBJECTIVE: Vacuolar H(+)-adenosine triphosphatase plays a pivotal role in pH regulation and molecular transport across the vacuolar membranes and is involved in cell proliferation and transformation. In the present study, possible involvement of vacuolar H(+)-adenosine triphosphatase in neointimal formation was investigated in an organ culture model of human saphenous vein. METHODS AND RESULTS: Cultured saphenous vein segments developed neointimal formation and marked thickening of the media within 14 days. Neointimal formation and medial thickening were completely inhibited by 10 nmol/L bafilomycin A(1), a selective inhibitor of vacuolar H(+)-adenosine triphosphatase, although structurally related macrolide antibiotics FK-506 and erythromycin were without an effect. The neointimal cells were positive for alpha-smooth muscle actin and vimentin but negative for desmin, indicative of myofibroblasts. The emergence of myofibroblasts was inhibited, and endothelial cells were preserved in the saphenous vein segments treated with bafilomycin A(1). Uptake of bromodeoxyuridine, a proliferation marker, by myofibroblasts was abrogated in the saphenous vein segments treated with 10 nmol/L bafilomycin A(1). Detection of apoptotic cells by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling concomitant with identification of desmin-expressing smooth muscle cells demonstrated that neointimal myofibroblasts, but not medial smooth muscle cells, that expressed desmin underwent apoptosis by treatment with bafilomycin A(1). CONCLUSIONS: These results suggest that vacuolar H(+)-adenosine triphosphatase may be involved in myofibroblast growth that contributes to neointimal formation and medial thickening in cultured human saphenous vein. Increased sensitivity of myofibroblasts, but not endothelial cells, and differentiated smooth muscle cells to bafilomycin A(1) may have potential therapeutic implications in the treatment for vein graft disease.

Actins↗