PubMed Health⌕ Search

Biomedical subjects

Kimihiro Komori

Publications and source records attributed to Kimihiro Komori.

15 recordsLinked to original sources
PubMed2003

Intramuscular gene transfer of FGF-2 attenuates endothelial dysfunction and inhibits intimal hyperplasia of vein grafts in poor-runoff limbs of rabbit.

We previously demonstrated that sustained disturbance of endothelium-dependent vasorelaxation and poor distal runoff in ischemic limbs were critical factors affecting the neointimal development of autologous vein grafts (VGs). Also, we recently showed the superior therapeutic potential of basic fibroblast growth factor (bFGF/FGF-2) boosted by the recombinant Sendai virus (SeV) for severe limb ischemia compared with that of vascular endothelial growth factor. Here, the effect of FGF-2 on neointimal hyperplasia of VGs was examined in a rabbit model of poor-runoff limbs. Two weeks after initial surgery for the induction of poor-runoff, SeV-expressing human FGF-2 (SeV-hFGF2) or that encoding firefly luciferase (109 plaque-forming units/head) was injected into the thigh and calf muscle. At that time, the femoral vein was implanted in the femoral artery in an end-to-end manner in some groups. FGF-2 gene-transferred limbs demonstrated significantly increased blood flow assessed not only by laser Doppler flow image but also by ultrasonic transit-time flowmeter (USTF). USTF also showed a significant increase in the blood flow ratio of the deep femoral artery to external iliac artery, indicating that collateral flow was significantly restored in the thigh muscles (P < 0.01). Reduction of neointimal hyperplasia was also observed in the VGs treated by SeV-hFGF2; these grafts demonstrated significant restoration of endothelium-dependent vasorelaxation. These findings thus extend the indications of therapeutic angiogenesis using SeV-hFGF2 to include not only limb salvage but also prevention of late graft failure.

Acetylcholine↗
PubMed2003

Buerger's disease in a 19-year-old woman.

A 19-year-old female college student had numbness and the sensation of coldness of her left toes. She had a 3-year smoking history. Gangrene of the left foot developed rapidly. Angiography revealed peripheral arterial occlusion of both legs and arms. Detailed laboratory examination excluded collagen disease, a hypercoagulable state, and juvenile atherosclerosis. Below-knee amputation of the left leg was performed. Typical histologic findings of Buerger's disease were observed in the crural arteries and saphenous veins. The clinical course was uneventful after the patient stopped smoking. This is the second case report of Buerger's disease in a woman in the second decade of life. It is important that a correct diagnosis of Buerger's disease be established, because the disease process is benign, compared with collagen disease, if the patient stops smoking.

Adolescent↗
PubMed2003

Mechanisms and prevention of intimal thickening of the autogenous vein grafts--possible involvement of nitric oxide--.

Platelet thrombosis, intimal hyperplasia, and the progression of atherosclerosis are the most important factors determining the patency of vein grafts for arterial occlusive disease. Interactions between aggregating platelets and the vessel wall play an important role in all of these processes. The endothelium modulates the underlying vascular smooth muscle by releasing nitric oxide (NO), a potent vasodilator and anti-aggregating substance. This review focuses on vascular modulation by NO in vein grafts.

Animals↗
PubMed2002

Essential role of monocyte chemoattractant protein-1 in development of restenotic changes (neointimal hyperplasia and constrictive remodeling) after balloon angioplasty in hypercholesterolemic rabbits.

BACKGROUND: Renarrowing of dilated arterial sites (restenosis) hampers the clinical benefits of coronary angioplasty. Infiltration and activation of monocytes in the arterial wall mediated by monocyte chemoattractant protein-1 (MCP-1) might be a major cause of restenosis after angioplasty. However, there is no direct evidence to support a definite role of MCP-1 in the development of restenosis. Methods and Results- We recently devised a new strategy for anti-MCP-1 gene therapy by transfecting an N-terminal deletion mutant of the MCP-1 gene into skeletal muscles. We used this strategy to investigate the role of MCP-1 in the development of restenotic changes after balloon injury in the carotid artery in hypercholesterolemic rabbits. Intramuscular transfection of the mutant MCP-1 gene suppressed monocyte infiltration/activation in the injured arterial wall and thus attenuated the development of neointimal hyperplasia and negative remodeling. CONCLUSIONS: MCP-1-mediated monocyte infiltration is necessary in the development of restenotic changes to balloon injury in hypercholesterolemic rabbits. This strategy may be a useful and practical form of gene therapy against human restenosis.

Angioplasty, Balloon↗
PubMed2002

Angiogenic gene therapy for experimental critical limb ischemia: acceleration of limb loss by overexpression of vascular endothelial growth factor 165 but not of fibroblast growth factor-2.

Recent studies suggest the possible therapeutic effect of intramuscular vascular endothelial growth factor (VEGF) gene transfer in individuals with critical limb ischemia. Little information, however, is available regarding (1) the required expression level of VEGF for therapeutic effect, (2) the related expression of endogenous angiogenic factors, including fibroblast growth factor-2 (FGF-2), and (3) the related adverse effects due to overexpression of VEGF. To address these issues, we tested effects of overexpression of VEGF165 using recombinant Sendai virus (SeV), as directly compared with FGF-2 gene transfer. Intramuscular injection of SeV strongly boosted FGF-2, resulting in significant therapeutic effects for limb salvage with increased blood perfusion associated with enhanced endogenous VEGF expression in murine models of critical limb ischemia. In contrast, VEGF165 overexpression, 5-times higher than that of baseline on day 1, also strongly evoked endogenous VEGF in muscles, resulting in an accelerated limb amputation without recovery of blood perfusion. Interestingly, viable skeletal muscles of either VEGF165- or FGF-2-treated ischemic limbs showed similar platelet-endothelial cell adhesion molecule-1-positive vessel densities. Maturation of newly formed vessels suggested by smooth muscle cell actin-positive cell lining, however, was significantly disturbed in muscles with VEGF. Further, therapeutic effects of FGF-2 were completely diminished by anti-VEGF neutralizing antibody in vivo, thus indicating that endogenous VEGF does contribute to the effect of FGF-2. These results suggest that VEGF is necessary, but should be delicately regulated to lower expression to treat ischemic limb. The therapeutic effect of FGF-2, associated with the harmonized angiogenic effects seen with endogenous VEGF, provides important insights into therapeutic angiogenesis.

Angiogenesis Inducing Agents↗
PubMed2002

Administration of a decoy against the activator protein-1 binding site suppresses neointimal thickening in rabbit balloon-injured arteries.

BACKGROUND: Transcription factor activator protein-1 (AP-1) is activated and upregulated in injured arterial smooth muscle cells in vivo, yet the exact role of the AP-1--related pathway in vascular disease in vivo has remained unclear. We examined the role of the transfer of synthetic double-stranded cis-element decoy oligodeoxynucleotides (ODNs) in balloon-injured rabbit carotid arteries and the effects of these ODNs on neointimal thickening. METHODS AND RESULTS: Transfection of fluorescein isothiocyanate--labeled ODNs using the hemagglutinating virus of Japan liposome method resulted in widespread distribution of fluorescent nuclear signals over the entire medial layer in injured arteries. Gel mobility shift assay revealed that AP-1 DNA binding was activated and that the AP-1 decoy reduced AP-1 DNA binding activity as a result of specific binding affinity to AP-1 in vivo. In morphometric analyses, AP-1 decoy led to a significant reduction in the neointimal area and a significant reduction in cell number and transforming growth factor-beta(1) production of human aortic smooth muscle cells under conditions of platelet-derived growth factor stimulation. CONCLUSIONS: Because AP-1 decoy transfection in vivo dramatically prevented neointimal thickening in balloon-injured arteries, AP-1 may be a useful molecular target for gene therapy to reduce restenosis.

Adult↗
PubMed2002

The usefulness of dipyridamole thallium-201 single photon emission computed tomography for predicting perioperative cardiac events in patients undergoing non-cardiac vascular surgery.

UNLABELLED: The aim of this study was to evaluate the usefulness of dipyridamole Tl-201 myocardium single photon emission computed tomography (201Tl-SPECT) for predicting perioperative cardiac events in patients with arteriosclerosis obliterans (ASO) and abdominal aortic aneurysm (AAA) undergoing non-cardiac vascular surgery. METHODS: Preoperative dipyridamole 201Tl-SPECT imaging in association with clinical risk assessment was performed in 224 consecutive patients (97 ASO and 127 AAA). RESULTS: The patients were classified into three groups, including low-risk (n = 173, 77%), intermediate-risk (n = 39, 18%), and high-risk (n = 12, 5%) groups according to the clinical risk stratification. The prevalence of reversible Tl-201 defect was significantly higher in the high-risk group than that in the low-risk group (83% vs. 14%, p < 0.001). In 180 patients who underwent vascular surgery, 9 patients (5.0%) had perioperative cardiac events, including heart failure (n = 1), unstable angina (n = 2), and other cardiac events such as arrhythmias (n = 6). The clinical variables including the clinical risk stratification did not significantly correlate with the perioperative cardiac events. In contrast, the reversible defect on 201Tl-SPECT was the only variable to predict perioperative cardiac events by a stepwise logistic regression analysis (odds ratio 7.0, 95% confidence interval 1.7-28.0, p = 0.007). It was also a significant predictor of perioperative cardiac events in a subgroup of low risk patients (odds ratio 11.6, 95% confidence interval 2.3-57.4, p = 0.004). The sensitivity and specificity of the reversible defect for predicting perioperative cardiac events were 55.6% and 84.8% in all operated patients, and 57.1% and 89.7% in low risk patients, respectively. CONCLUSIONS: The preoperative dipyridamole 201Tl-SPECT was useful for predicting perioperative cardiac events in patients with vascular diseases, even in patients identified as having a low risk based on the clinical risk assessment.

Aged↗
PubMed2002

Solitary fibrous tumor in the retroperitoneal space: report of a case.

Solitary fibrous tumors (SFTs) are spindle-cell neoplasms originally described in the pleura. It is now known that these tumors can develop in many sites. This report describes the case of a well-circumscribed tumor located around the superior mesenteric artery (SMA), which was initially thought to be either a superior SMA aneurysm, a lymphoma, or a neurogenic tumor. Histological examination demonstrated the tumor to be composed of a cellular proliferation of ovoid to spindle cells with a fine collagenous matrix in the short fascicles. Immunohistochemical staining was strongly positive for CD34 and negative for factor VIII, cytokeratin, desmin, and muscle-specific actin (HHF-35). These findings suggested a diagnosis of SFT in the retroperitoneal space. To our knowledge, this is the first report of an SFT located around the SMA. Based on the above findings, it is important to include SFT in the differential diagnosis of retroperitoneal tumors located around the SMA.

Carcinoma↗
PubMed2002

Differences in endothelial function and morphologic modulation between canine autogenous venous and arterial grafts: endothelium and intimal thickening.

BACKGROUND: Late graft failure is still a problem for vascular surgeons. A previous study showed superior patency of arterial grafts compared with venous grafts. In this review we discuss the differences in functional and morphologic modulation of experimental autogenous venous and arterial grafts. RESULTS: In canine venous grafts, the endothelium of the graft was denuded and recovered within 3 or 4 weeks. In contrast, in arterial grafts, denudation of the endothelium was minimal, and no platelet adherence was observed. Instead, nearly normal intact endothelial cell surface had covered the intima within 3 days after grafting. The histologic findings for arterial grafts thus were quite different from those for venous grafts. Different responses to flow changes between venous and arterial grafts were observed. In the venous grafts, pronounced intimal thickening was associated with impairment of endothelial responses, whereas in the arterial grafts, intact endothelial function and no intimal thickening were observed. CONCLUSIONS: The intact endothelial function and absence of intimal thickening under the arterial grafts may explain the superior patency of autogenous arterial grafts in comparison with venous grafts.

Animals↗
PubMed2002

Local blood serotonin and soluble P-selectin levels during percutaneous transluminal balloon angioplasty and primary stenting of the iliac artery.

BACKGROUND: The activation of platelets or leukocytes plays an important role in development of intimal hyperplasia. We investigated whether the local blood serotonin and soluble P-selectin levels changed during endovascular therapy of the iliac artery. METHODS: Blood samples were obtained from the iliac artery of 18 lower limbs undergoing percutaneous balloon angioplasty alone (8 limbs, group I) or percutaneous balloon angioplasty and primary stenting (10 limbs, group II). The serotonin levels in platelet-poor plasma were measured in all limbs. In group I the urinary level of the serotonin metabolite 5-hydroxyindoleacetic acid was also measured 24 hours before and 24 hours after the procedures. The soluble P-selectin levels were measured in the 6 patients in group II. RESULTS: Before angioplasty the mean (+/- SEM) serotonin concentrations were 1.2 +/- 0.2, 1.2 +/- 0.4, and 1.2 +/- 0.3 ng/mL in all cases, group I, and group II, respectively. After angioplasty these values changed to 1.7 +/- 0.4 (P =.0750), 1.2 +/- 0.4 (P =.8001), and 2.1 +/- 0.6 ng/mL (P =.0529), respectively. In group I urinary 5-hydroxyindoleacetic acid concentrations 24 hours before and 24 hours after the procedures were 0.0026 +/- 0.0004 and 0.0031 +/- 0.0006 mg/mg creatinine, respectively (P =.2566). In group II the soluble P-selectin levels significantly increased after intervention, from 26.0 +/- 5.7 to 33.9 +/- 5.3 ng/mL (P =.0296). CONCLUSIONS: Although the serotonin levels did not change significantly, the soluble P-selectin levels increased significantly after intervention. Leukocyte activation may therefore contribute to the progression of restenosis after peripheral endovascular therapy.

Aged↗
PubMed2002

Comparison of the long-term results between surgical and conservative treatment in patients with intermittent claudication.

BACKGROUND: The optional therapeutic strategy for patients with intermittent claudication remains controversial. In this study, we investigated the influence of surgical and conservative therapies on improving the quality of life in patients with intermittent claudication. METHODS: We analyzed 427 patients who were admitted to our hospital with intermittent claudication in their legs during a 15-year period from January 1984 to December 1999. We separated them into 2 groups; 259 patients (362 legs) were treated surgically and 168 patients were treated conservatively. RESULTS: At the suprainguinal and infrainguinal (above knee) region, the surgery group showed significantly better rate of improvement than did the conservative group, but in the infrainguinal (below knee) region, there was no significant difference between the 2 groups. The 3-year and 5-year patency rates for the arterial reconstruction of the suprainguinal and infrainguinal region was satisfactory, but that of the infrainguinal region was not very good even if an auto vein graft was used. CONCLUSIONS: Aggressive surgical treatment is therefore recommended in patients whose distal anastomotic region is above the knee, because there are great benefits from surgical reconstruction. However, in patients whose distal anastomotic region is below the knee, conservative treatment might be just as effective as surgery.

Aged↗
PubMed2002

Gene therapy in vascular surgery comes of age.

In the last decade, gene therapy for cardiovascular diseases has been becoming a reality. However, although numerous successful experimental studies have suggested possible strategies of gene therapy for cardiovascular disorders, the clinical outcome remains limited. Because cardiovascular diseases are the result of complex causes, there is no exact answer to the following question: Which is the best gene to treat vascular diseases? In addition, current limitations include less clinically relevant vectors regarding both gene-transfer efficiency and safety, and at present, most efforts are focused on identifying more effective therapeutic genes, as well as developing more effective vectors. Furthermore, greater pathophysiologic understanding of these diseases, including vein-graft remodeling and ischemic limbs, is required. Regarding the relevant vector, we recently developed a novel mononegavirus-based gene-transfer vector, namely recombinant Sendai virus, which has shown dramatically superior gene-transfer efficiency to other vectors, including adenovirus, in several organs (eg, the vessel wall and skeletal muscles). These efforts now offer new possibilities to get more fruits in the field of gene therapy for vascular surgery.

Combined Modality Therapy↗
PubMed2002

Intraluminal gene transfer of endothelial cell-nitric oxide synthase suppresses intimal hyperplasia of vein grafts in cholesterol-fed rabbit: a limited biological effect as a result of the loss of medial smooth muscle cells.

BACKGROUND: The intimal hyperplasia of vein grafts is a major cause of late graft failure and is more pronounced under hyperlipidemia. We previously reported that endothelial cell (ec)-type nitric oxide synthase (NOS) gene transfer inhibited graft intimal hyperplasia under poor runoff conditions. However, little information is available on either ecNOS gene transfer or intimal thickening under hypercholesterolemia. METHODS: Using the hemagglutinating virus of Japan liposomes, bovine ecNOS complentary DNA (5000 hemagglutinating activity units/mL) was transfected intraluminally to the right jugular vein, and these veins were then implanted as reversed vein grafts in an end-to-side fashion to the ipsilateral carotid artery. RESULTS: The cyclic guanosine 3',5'-monophosphate content of the ecNOS vein significantly increased in the grafts at 4 days after gene transfer, but the levels were only 25% greater than those found in the untreated veins. An immunohistochemical analysis at the same time suggested a large loss of medial smooth muscle cells that might have led to a reduction in the exogenous gene expression. The neointima of the ecNOS grafts was significantly reduced 4 weeks after implantation (P <.05), but the effect of ecNOS was limited to about a 30% inhibition. This reduction was associated with a reduced population of proliferating cells and decreased macrophage accumulation in the graft wall. CONCLUSIONS: These results demonstrated that the ecNOS gene transfer suppressed intimal hyperplasia of the vein grafts under hyperlipidemic conditions. However, this effect may be limited because of the smooth muscle cell loss related to the use of an intraluminal delivery methods. These data lead to speculation that the outcome of ecNOS gene transfer could be improved using different methods of gene delivery.

Animals↗
PubMedDate not supplied

Gore-Tex jump graft for portal vein thrombosis following living donor liver transplantation.

Portal vein thrombosis is a rare surgical complication following liver transplantation, which remains a cause of graft loss and death. We describe here the treatment of portal vein thrombosis following living donor liver transplantation using an extended left lobe graft. The patient was treated with a Gore-Tex vascular jump graft extra-anatomically interposed between the recipient superior mesenteric vein and the donor umbilical vein. This technique allowed the hepatic hilum to be left untouched and supplied suitable blood flow to the hepatic allograft. Our experience suggests that this innovative technical solution can be helpful in the effort to rescue cases of hepatic allograft with vascular complications.

Adult↗