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Biomedical subjects

Y Noishiki

Publications and source records attributed to Y Noishiki.

At least 19 recordsLinked to original sources

Esterification of beta-chitin via intercalation by carboxylic anhydrides.

beta-chitin is known to form intercalation complexes with aliphatic alcohols and amines. We found that it also forms complexes with carboxylic anhydrides. When the beta-chitin-acetic anhydride complex was heated to 105 degrees C, the hydroxyl groups of chitin were acetylated by a host-guest reaction, maintaining the host's crystal structure. Structures of complex and acetylated products were analyzed by X-ray diffraction, (13)C CP/MAS NMR, and infrared spectroscopy. The maximum degree of substitution (DS) was close to 1.0, suggesting regioselective esterification at the C6 position of chitin. Partially acetylated beta-chitin with a DS of 0.4 could incorporate various guest species that are difficult to be incorporated by original beta-chitin. In contrast, beta-chitin acetate with a DS of 1 lost the ability to form a complex. Intercalation complexes of beta-chitin with cyclic anhydrides (succinic and maleic) also underwent esterification by heating, and the products with a DS of approximately 1 dissolved in aqueous alkali, apparently as the result of the dissociation of introduced carboxyl groups. These phenomena are potentially useful in controlling the complexation ability of beta-chitin and the preparation of regioselectively esterified chitin derivatives.

Acetates↗

A honeycomb collagen carrier for cell culture as a tissue engineering scaffold.

As a three-dimensional carrier for cell culture, a honeycomb structure cell scaffold was created from atelopeptide collagen Types I, II, and III. The diameter of the honeycomb pores ranged from 100 to 1,000 microm. The depth of the pores was from 10 to 3,000 mm. The scaffold was elastic and hard. Creation of various shapes was easy, and these shapes were easily maintained. Human fibroblasts, CHO-K1, BHK-21, and bovine endothelial cells were cultured with the scaffold. The growth curves of these cells were satisfactory. These results suggest that this carrier is a suitable scaffold for cell culture and will be useful as a three-dimensional tissue engineering scaffold.

Animals↗

Clinical long-term results of vascular prosthesis sealed with fragmented autologous adipose tissue.

Tissue engineering can improve the former limitations of artificial organs. This article reports the long-term clinical results of grafts constructed with fragmented autologous adipose tissue. We did a retrospective analysis of a series of 53 patients with lower leg ischemia that received 69 fragmented adipose tissue (FAT) grafts implantation at our institution. The mean follow-up period was 36.0 months. After 1, 2, 3, and 5 years, the primary potency rates were 85.3, 83.3, 73.8, and 67.7%, respectively. The lumen of occluded areas not only at anastomotic sites but also in areas far from the anastomotic sites was occupied by a thickened neointima, which had a great number of capillary blood vessels, elastic laminae, smooth muscle cells, fibroblasts, and collagen fibers. This type of intimal hyperplasia was a characteristic finding in the FAT grafts. From the results of this clinical trial, we conclude that the FAT grafts are acceptable as vascular prostheses for ischemic lower extremities. The intimal hyperplasia at sites far from the anastomotic lines suggested the possibility of neointima formation throughout the luminal surface of the grafts.

Adipose Tissue↗

Midterm results of stent-graft repair for thoracic aortic aneurysms: computed tomographic evaluation.

Midterm observation of endovascular surgery using a fabric-covered stent graft for thoracic aortic aneurysms is discussed with postoperative follow-up findings based on regularly performed thoracic computed tomography (CT). From 1996 to 1999, 20 patients with thoracic aortic aneurysm underwent stent-graft placement in our hospital. One year follow-up CT results after placement were obtained for 17 patients. The CT scans found that there were both thrombosis and size reduction of aneurysm in 8 patients (46%), thrombosis without size reduction in 2 (13%), a new ulcerlike projection (ULP) in 3 (19%), persistent minor endoleakage in 2 (13%), a new endoleak in 1 (6%), and a recurrent endoleak from intercostal arteries in 1 (6%). The new ULP formation seemed to be a peculiar problem stemming from an intimal injury caused by edges of the stent. Therefore, we recently adopted a new spiral stent instead of the previous stent to avoid the injury. The new endoleak suggested that aneurysmal thrombosis without size reduction could cause the aneurysm to develop recurrent endoleaks. From these findings, we concluded that midterm observation of stent-graft repair for thoracic aortic aneurysms did not give satisfactory results. In order to improve the results of endovascular surgery using stent-grafts, we need to develop safer stent grafts with a reliable design to prevent endoleaks and to avoid intimal injury of the aorta. We also hope to develop effective technologies that can accelerate organization of thrombus in the aortic aneurysm after stent-graft placement.

Adult↗

Introduction of tissue engineering concepts into the field of endovascular grafts: an attempt to solve endoleakage problems of endovascular grafts implanted in aortic aneurysms.

To solve endoleakage problems of endovascular prostheses inserted in aortic aneurysms, a concept originating from tissue engineering was proposed. We proposed that in order to accelerate the thrombus inside the aneurysm, three major factors for successful tissue engineering, i.e., appropriate cells, extracellular matrices, and growth factors, should be introduced into a space between the endovascular grafts and the aneurysm. As a simulation model in animals, two kinds of fabric vascular prostheses were used. One was a small graft used as an endovascular graft and another was a large graft as an envelope for the small graft, used as the aneurysm wall. Adipose tissue fragments with fresh blood coagula were injected between the two grafts. The control was a preparation without tissue fragments. Two months and a half after surgery, the test group showed complete connective tissue formation in the space between the two grafts, but in the control, brownish thrombus remained. From this experiment, we speculated that tissue fragment transplantation will accelerate connective tissue formation of the thrombus, and this complete organization of the thrombus might reduce endoleakage.

Adipose Tissue↗

Experimental study of materials for patch graft on right ventricular outflow tract under extracorporeal circulation in dogs--comparison between Denacol EX-313-treated bovine jugular vein graft and expanded polytetrafluoroethylene (EPTFE) graft.

A comparison between a bovine jugular vein treated with a hydrophilic polyepoxy compound cross-linker (Denacol), and expanded polytetrafluoroethylene (EPTFE), an artificial material, as a patch graft for the reconstruction of the right ventricular outflow tract under extracorporeal circulation in dogs, as if they had pulmonic stenosis, was made. Hemodynamic and histological examinations were conducted two weeks after the transplantation. Hemodynamic problems were not observed in either the Denacol or EPTFE groups. Macroscopically, organization of new tissue on the graft surface was more marked in the EPTFE group than in the Denacol group, and newly-formed tissue was seen surrounding the border of the graft and burying it in the EPTFE group. In the Denacol group, microscopic findings revealed the presence of inflammatory cells and fibroblasts, and an invasion of the graft by collagen fibers and elastic fibers. In the EPTFE group, there was minimal cellular infiltration of the graft and a thick layer consisting of collagen fibers and fibroblasts was observed around the graft. These results indicated that two weeks after transplantation the graft was better assimilated and organized with blood vasculature in the patch graft in the Denacol group than in the EPTFE group.

Animals↗

Autologous tissue-fragmented extracardiac conduit with rapid, stable endothelialization due to angiogenesis.

OBJECTIVES: Autologous angiogenic cytokines are known to activated by mincing stimulation, and well regulated in vivo. We applied this tissue fragmentation technique to a low-pressure pulmonary extracardiac conduit to obtain rapid endothelialization and stable neointima formation due to angiogenesis. METHODS: Subcutaneous adipose tissue was obtained, minced, suspended, and sieved through highly porous fabric vascular prosthesis by pressurized injection. The adipose tissue fragmented graft with an autologous fresh pericardial monocusp valve was implanted between the right ventricle and the pulmonary artery in 13 dogs. The same grafts without fragments were implanted in 8 dogs as controls. No anticoagulation therapy was given. RESULTS: Grafts were removed 6 to 1,128 days after implantation. In the developed grafts, angiogenesis occurred throughout the interstices of the graft wall from the adventitial side, and host cells proliferated and migrated. Endothelialization was completed throughout developed grafts at 2 weeks. The intima was still thin up to 1,128 days and free of degenerative changes. In control grafts, however, capillary infiltration was limited to perigraft tissue at 2 weeks and endothelialization was not completed by 3 months. Under the endothelial cell layer, laminal elastic fibers were formed through the developed graft wall by 4 months and still maintained at 1,128 days. CONCLUSIONS: The results demonstrated that adipose tissue fragmented extracardiac conduits induce rapid endothelialization and maintained thin intima with laminal elastic fibers. Long-term durability is expected based on results from using this technique in a low-pressure pulmonary system in dogs.

Adipose Tissue↗

Age dependency of neointima formation on vascular prostheses in dogs.

Neointima formed quickly on vascular prostheses implanted in young dogs but not in aged dogs. Previously, we found that impeding neointima formation on vascular prostheses occurred more frequently in aged animals. From these observations, we hypothesized that neointima formation was age-dependent in dogs. To test the hypothesis, 26 fabric Dacron vascular prostheses were analyzed. Half of them were retrieved from aged dogs (more than 13 years old) while the other half were from young ones (less than 1 year old). The grafts were harvested at 8 weeks and 3 months after implantation. The graft surfaces were photographed and analyzed by computer for the ratio of the areas with and without thrombus. Light and scanning electron microscopic observation revealed that most of the thrombus-free areas were lined with endothelial cells. Then the endothelialized areas were calculated. Using data obtained from macroscopic, light microscopic, and scanning electron microscopic observations, the arithmetic means were calculated as the degree of neointima formation. In young animals, the degrees at 8 weeks and at 3 months were 89.1 +/- 8.5% (mean +/- SD) and 95.7 +/- 3.3%, respectively. In old animals, they were 27.9 +/- 5.9% and 31.5 +/- 6. 8%, respectively. From these results, we concluded that neointima formation was age-dependent in dogs.

Aging↗

A comparative study between hypothermic and normothermic cardiopulmonary bypass in open heart surgery in dogs--effects on systemic hemodynamics.

Open heart surgery was performed on two groups of dogs under extracorporeal circulation with or without hypothermia to investigate hemodynamic changes during extracorporeal circulation. During hypothermic cardiopulmonary bypass (CPB), arterial O2 tension and postoperative blood pressure were favorably maintained, indicating that hypothermic extracorporeal circulation can be performed for a long period of time. On the other hand, during normothermic CPB, the average surgical duration was significantly shorter, and marked shifts in the concentrations of various enzymes were suppressed. However, due to reductions in arterial O2 tension, the length of cardiac arrest time was restricted, demonstrating that this method is suitable for performing extracorporeal circulation for CPB of relatively short duration. If circulation circuitry can be improved, such as through the development of a surpassing oxygenator, normothermic CPB would incur less stress on the body, thus making it preferential to hypothermic CPB in most cases.

Animals↗

Succinylated collagen crosslinked by thermal treatment for coating vascular prostheses.

Vascular prostheses coated with collagen carefully prepared to avoid contamination were tested to see if it could induce endothelial cell lining throughout the graft surface in a natural way. The collagen fibers were succinylated. Hydrogel produced with the succinylated collagen was used for the sealant to reduce the amount of solid substance. To avoid contamination and the side effects of chemical reagents, the collagen thermally crosslinked under sterile conditions. A suspension of the collagen fibers was enmeshed in the interstices of Dacron fibers of fabric prostheses, which were then thermally crosslinked at 130 degrees C for 20 h. The prostheses were porous when the collagen fiber network was dry. Under wet conditions, however, the water permeability of the grafts was reduced to 0.1 ml/min from the 1,250 ml/min of the original prostheses. Three weeks after implantation in the abdominal aortas of dogs, 81.2 +/- 11% of the luminal surface was macroscopically thrombus free, and 56 +/- 14% was endothelialized. More than 95% of the coated collagen had been absorbed. Numerous fibroblasts had migrated into the graft walls, and capillary blood vessels had infiltrated the inside of the graft walls without foreign body reaction. In the controls, thrombus free areas averaged 9.0 +/- 5%, and endothelialized areas averaged 5.2 +/- 4%. Many giant cells, plasma cells, and lymphocytes had migrated into the graft walls, but no fibroblasts. These results suggest that rapid endothelialization is possible when clean collagen is used.

Animals↗

Choice, isolation, and preparation of cells for bioartificial vascular grafts.

Preparation of cells and tissues for bioartificial vascular grafts is discussed from the viewpoint of tissue engineering. In general, a neointima is not formed on vascular prostheses except at the anastomotic sites. Graft surfaces do not heal and are covered with fresh thrombi for a long period of time after implantation. The delayed healing is, so to speak, an intractable ulcer of the vascular wall. To overcome this problem, we have developed a tissue fragment transplantation method. We consider that neointima formation of vascular prostheses after implantation is a product of tissue engineering in vivo. Therefore, 3 essential elements for tissue engineering, i.e., cells, extracellular matrices, and cytokines, are required for neointima formation. Synthetic vascular prostheses lack one or more of these elements. In this study we demonstrated a standard healing process of fabric vascular prostheses and an antithrombogenic polymer graft using animal models. Then we showed the tissue fragment transplantation method using venous tissues, adipose tissues, and bone marrow. This method provided the 3 essential elements to the prostheses. To allow these elements to be actively engaged in neointima formation, we treated cells and tissues as clumps without enzymatic digestion. We also took advantage of the in vivo environment. With the results we demonstrate our way of thinking in relation to bioartificial vascular grafts.

Adipose Tissue↗

Use of a bovine jugular vein graft with natural valve for right ventricular outflow tract reconstruction: a one-year animal study.

OBJECTIVE: We evaluated a bovine jugular vein graft with a natural trileaflet valve for right ventricular outflow tract reconstruction in a canine study for an entire year. METHODS: Heparinized bovine jugular vein grafts with a natural valve cross-linked with a hydrophilic polyepoxy compound of 18 to 20 mm in internal diameter were implanted in the right ventricular-pulmonary arterial position in eight dogs, and the main natural pulmonary artery was ligated. Anticoagulants were not used after implantation. Five grafts were retrieved on day 182 after implantation and the other three grafts on days 196, 375, and 385, respectively, and were inspected by macroscopic and microscopic observation. Cardiac catheterization, followed by angiography and echocardiography, was done just before graft retrieval. RESULTS: No graft kinking or regurgitation of the valve was observed. Echocardiography showed natural valve motion without thickening of the leaflets. Blood pressure in the conduits ranged from 18/9 to 31/4 mm Hg, in the right ventricle from 18/4 to 40/0 mm Hg, and the gradient varied from 0 to 14 mm Hg. The explanted conduits maintained their original shape, softness, and pliability with good coaptation of valves, without calcification or degenerative changes, except for one leaflet with slight deformation. In microscopic observation, endothelial cells lined the luminal surface of the conduit except for the areas adjacent to the valve. CONCLUSION: The graft worked perfectly as a right ventricular-pulmonary arterial valved conduit without anticoagulant therapy for a long time.

Animals↗

[Calcified EPTFE vascular prosthesis in the Blalock-Taussig shunt after 4 years of implantation: a case report].

A boy was born with asplenia, complete endocardial cushion defect, pulmonary atresia and transposition of great vessels. Modified Blalock-Taussig (BT) shunt procedure to the right pulmonary artery was performed using an expanded polytetrafluoroethylene (EPTFE) vascular graft three days after born in 1990. At one year old, left BT-shunt procedure was also performed. At four years old (1994), bi-directional Glenn procedure was performed. At that time, a piece of the EPTFE graft in the BT-shunt at the pulmonary anastomosis, was removed and observed macroscopically and microscopically. It was patent with a neointima and thrombi. Microscopically, multiple calcified legions and many macrophages were found in the graft wall. Thrombi on the graft lumen, which were suspected to be formed different occasions, were observed. A thin neointima with an endothelial cell layer near the anastomosis was remarkable. To our knowledge, this is the first report of such calcified lesions in the EPTFE vascular graft wall within 4 years in the BT-shunt position in an infant.

Arteriovenous Shunt, Surgical↗

Autocrine angiogenic vascular prosthesis with bone marrow transplantation.

Synthetic vascular prostheses are foreign bodies, so that blood coagulation can occur on their luminal surfaces, causing graft occlusion very frequently in prostheses of small diameter. A vascular prosthesis needs angiogenesis for endothelialization of the luminal surface, as endothelial cells have natural and permanent antithrombogenic properties. To induce capillary growth into the graft, we developed a method of transplanting bone marrow cells, which are primitive, strong enough to survive, and create blood cells, resulting in the inducement of capillary growth. In an animal experiment, marrow cells were infiltrated into the walls of long-fibril expanded polytetrafluoroethylene (ePTFE) vascular grafts. The grafts were implanted in the abdominal aortic position of 24 dogs autologously. Marrow cells survived and continued exogenous hemopoiesis for up to six months and were immunohistochemically reactive to basic fibroblast growth factor (bFGF). All the grafts older than three weeks had complete endothelialization and maintained their patency. Twenty grafts without bone marrow were implanted as controls. Endothelialization was present at anastomotic sites, but other areas were covered with fresh thrombi. Four out of seven control grafts were patent with endothelial cell lining at six months, but three were occluded and one of the four grafts was still covered with a thrombus layer. Bone marrow with its unique native properties produced autocrine angiogenicity in the graft.

Animals↗

The use of epoxy patch grafts for the repair of experimentally-created diaphragmatic defects in dogs.

Canine pericardium which had been treated with polyepoxy compounds (Denacol EX-313) was used as a patch graft for the correction of experimentally-created diaphragmatic defects in five dogs belonging to the same litter. Clinical, macroscopic and histological examinations were conducted every month up to five months after suturing of the patch graft. Clinical examination of the patch graft showed no apparent abnormalities. Macroscopic examination conducted during autopsy showed that the patch graft maintained adequate elasticity for five months after suturing, the surface of the patch graft was covered with a thin membrane and neovascularization was observed. Histological examination showed that the surface of the patch graft was covered with a thin membrane. Inflammatory tissue reactions were observed at one month, but gradually decreased from the second month onwards. In addition, the patch graft had excellent tissue affinity.

Animals↗

[Evaluation of blood absorption, hemostatic ability and purity of a polyepoxy compound cross-linked cotton type collagen hemostat].

A polyepoxy compound cross-linked cotton type collagen hemostat (CCH) made of highly purified atelocollagen in a fine filament shape was developed. To evaluate blood absorption, hemostatic ability and purity of the CCH, Avitene and Oxycel were used for comparison. Blood absorption speed of the CCH was faster than Avitene and Oxycel. The handling characteristics of the CCH were much better than those of Avitene and Oxycel. Hemostatic ability was better in the CCH compared to Avitene in a canine study. The purity of the CCH was better than in Avitene which contained albumin and other proteins. Those results suggest that the developed hemostat with excellent blood absorption, handling characteristics, hemostatic ability and purity, could be useful in clinicals.

Absorption↗