Biomedical subjects

T Oka

Publications and source records attributed to T Oka.

1,508 records · Page 84Linked to original sources

PubMedDate not supplied

Effects of gamma-ray irradiation on superoxide dismutase activity and lipid peroxide level in mouse salivary glands.

The effect of local gamma-ray irradiation on the enzymatic activity of superoxide dismutase in salivary glands was examined. Mice received a single dose of 60Co gamma-ray irradiation in the range of 3 to 24 Gy to their neck regions. The enzymatic activity in salivary glands was decreased significantly at the 7th day and almost recovered at the 14th day after irradiation with over 6 Gy. The elevation of the lipid peroxide levels in the submandibular gland followed by the leakage of superoxide dismutase from the glands into the blood plasma was observed after irradiation, indicating radiation-induced membrane damage of salivary glands.

Animals↗

PubMedDate not supplied

Angiopeptin as a potent inhibitor of myointimal hyperplasia. Systemic injection and local administration via impregnation in a biodegradable polymeric gel.

We studied a pharmacologic approach using a potent peptidyl antiproliferative agent, angiopeptin, to prevent the myointimal hyperplasia that occurs as a diseased vessel is replaced with an artificial graft or treated by an intravascular device. In vitro cell culture studies showed that the proliferative potential of smooth muscle cells was dose dependently reduced, whereas the migratory response was reduced to a lesser degree. In a well defined injured rat artery model, in which a denuded aorta was prepared by collagenase treatment, followed by isotransplantation, a remarkable suppressive effect of angiopeptin on myointimal hyperplasia was observed with daily subcutaneous injection. Local sustained release from a biodegradable polymeric gel coated on an injured vessel was also effective in the prevention of myointimal hyperplasia. Slightly retarded endothelial regeneration was noticed. The potential application to small caliber artificial grafts is discussed.

Administration, Topical↗

PubMedDate not supplied

Phenotypic modulation of smooth muscle cells in intima-media incorporated hybrid vascular prostheses.

Hierarchical hybrid vascular grafts were constructed with an endothelial cell (EC) monolayer and hybrid medial layer composed of smooth muscle cells (SMCs) and type I collagen gel. The grafts, implanted into canine carotid arteries for up to 12 weeks, were ultrastructurally examined with a transmission electron microscope. Before implantation, SMCs incorporated into hybrid media were round and intracellularly filled with synthetic organelles such as rough endoplasmic reticula, mitochondria, free ribosomes, and Golgi complexes. Two weeks after implantation, bipolar spindle shaped SMCs still remained in a synthetic phenotype. At 12 weeks, circumferentially aligned SMCs were abundant in contractile apparatus such as myofilaments, dense bodies, and basement membranes. In a morphometric evaluation, the populations of three phenotypic SMCs (synthetic, intermediate, and contractile SMCs) were quantified. At 2 weeks, the proportions were 50.5, 41.8, and 7.7% for synthetic, intermediate, and contractile phenotypes, respectively. At 12 weeks, they were 9.9, 26.2, and 63.8%. These findings indicated that SMCs incorporated into hybrid grafts were transformed from a synthetic to a contractile phenotype under pulsatile stressed conditions after 12 weeks in vivo. Thus, the intima/media incorporated hybrid graft reconstructed a vessel wall similar to a native one in terms of structure and function.

Animals↗

PubMedDate not supplied

In vitro reconstruction of hybrid vascular tissue. Hierarchic and oriented cell layers.

Hybrid vascular tissue was hierarchically reconstructed in vitro. A hybrid medial layer composed of type I collagen gel, in which SMCs derived from a mongrel dog were embedded, was formed on the inner surface of a compliant porous polyurethane graft (internal diameter = 3 mm). Endothelial cells (ECs) from the same animal were seeded and cultured on the hybrid media to build an intimal layer. Subsequently, hierarchically structured grafts constructed in this manner were subjected to pulsatile flow (flow rate: 8.5 ml/min; frequency: 60 rpm; amplitude: 5% of graft outer diameter) of culture medium (Medium 199 supplemented with 20% fetal calf serum). After stress loading for as long as 10 days, tissues were morphologically investigated with a light microscope and a scanning electron microscope. Inner surfaces of the hybrid tissues were covered with EC monolayers that aligned along the direction of the flow (i.e., longitudinally). However, SMCs beneath the intima aligned in the circumferential direction. These cellular orientations resembled those in native muscular arteries. The pulsatile stress loaded hybrid tissue mimicked native muscular arteries with respect to hierarchic structure and cellular orientation. In vitro mechanical stress loading on a hybrid graft might provide a high degree of integrity in terms of tissue structure that promises high tolerance toward hydrodynamic stress and regulation of vasomotor tone upon implantation.

Animals↗

PubMedDate not supplied

Mechanical stress induced cellular orientation and phenotypic modulation of 3-D cultured smooth muscle cells.

The effect of periodic stretch on cellular orientation and intracellular ultrastructure of three-dimensionally (3-D) cultured arterial smooth muscle cells (SMCs) was investigated. Ring shaped hybrid tissues were prepared by thermal gelation of a mixed solution of Type I collagen and SMCs derived from bovine aorta. The gels were subjected to three modes of stress loading: floated (control), stretched isometrically (static stress), and periodically stretched and recoiled with 10% amplitude at 60 rpm frequency (dynamic stress). After 4 weeks of stress loading, the gels were morphologically investigated with a light microscope and a transmission electron microscope (TEM). Irrespective of static or dynamic stress loading, SMCs in stress loaded gels exhibited an elongated bipolar spindle shape and were oriented parallel to the direction of stretch, whereas those in control gels were polygonal shaped and randomly oriented. TEM observation showed that SMCs in control and static stress loaded gels were intracellularly filled with organelles, such as rough endoplasmic reticulum, free ribosomes, Golgi complexes, and mitochondria, indicating that the cells were of the synthetic phenotype. On the other hand, SMCs in dynamic stress loaded gels tended to have increased contractile apparatus, such as myofilaments, dense bodies, and basement membranes, suggesting that periodic stretch plays an important role in phenotypic modulation of SMCs from the synthetic to the contractile state, as well as cellular orientation.

Animals↗

PubMedDate not supplied

Small diameter vascular prostheses with incorporated bioabsorbable matrices. A preliminary study.

The authors have designed small diameter vascular prostheses with incorporated matrices that can be absorbed into a growing anastomotic neointima. First, a gelatin-heparin complex was coated on the inner surface of tubular ultrafine polyester fabrics presealed with heat denatured albumin. Second, to control the bioabsorption rate, the prepared grafts were cross-linked with polyepoxy compounds for 3 days (Group I; n = 14) or 5 days (Group II; n = 4). These grafts, 3 mm in diameter and 4 cm long, replaced the carotid arteries of nine mongrel dogs weighing 9.5-14 kg. Six of eight (75%) grafts in Group I were patent when the animals were killed 4 weeks after surgery. Doppler sound examination revealed that the remaining six were patent for 16 weeks. In Group II, three of four (75%) grafts were patent when the animals were killed 8 weeks after surgery. In both groups, scanning electron microscopic study showed neither platelet aggregation nor fibrin formation on the midportion. However, these two groups significantly differed in histology. In Group I, thin anastomotic neointima advanced over the mostly absorbed gelatin-heparin complex layer. Connective tissue was well formed around the polyester scaffold. In contrast, thick neointima advanced over the gelatin-heparin complex layer that still remained on the luminal surface in Group II. These results suggest that the gelatin-heparin complex, when cross-linked adequately, could simultaneously function as a temporary antithrombogenic surface and as an excellent substructure of an anastomotic neointima.

Anastomosis, Surgical↗

PubMedDate not supplied

Biliary stricture due to mucosal hyperplasia of the common bile duct: a case report.

A 71-year-old man with a tumorous lesion of the common bile duct is presented. Although histological examination of tumor biopsy specimens taken at the time of duodenoscopy or percutaneous transhepatic choledochoscopy showed mucosal hyperplasia, cancer could not be ruled out; therefore, the patient underwent pancreatoduodenectomy. However, histology showed nodular mucosal hyperplasia and an ectopic pancreas adjacent to the papilla of Vater, which was suspected to have contributed to the development of the lesion by stimulating the mucosa of the papilla and the distal common bile duct.

Aged↗

PubMedDate not supplied

Promoter-independent loss of mRNA and protein of the Rb gene in a human hepatocellular carcinoma.

BACKGROUND: Inactivation of the retinoblastoma (Rb) gene is considered to play a fundamental role in the genesis and progression of several human cancers. In retinoblastoma, the inactivation of Rb promoter by mutations or hypermethylation has been reported. Although genetic changes of Rb gene have been described in hepatocellular carcinoma (HCC), an epigenetic change such as hypermethylation of the Rb promoter as reported in retinoblastoma has not been described. MATERIALS AND METHODS: We examined the hypermethylation in the promoter region of Rb gene by restriction fragment length polymorphism in 19 HCCs, as well as the expression of Rb mRNA and protein by RT-PCR and by immunoblotting, respectively. RESULTS: We found no evidence of hypermethylation in the promoter region of the Rb gene in all HCCs analyzed. However, the expression of Rb mRNA and protein was lost in one HCC, and no mutation was detected in the Rb promoter region of this patient. The inactivation of Rb promoter by hypermethylation or by inhibition of binding of transcription factors due to point mutations did not contribute to the loss of mRNA and protein in the patient. CONCLUSIONS: Hypermethylation in the Rb promoter region appeared to have little causal effect on HCC.

Aged↗

PubMedDate not supplied

Reciprocal gene expression of rat fibroglycan and beta-actin during the course of regeneration after D-galactosamine liver injury.

BACKGROUND/AIMS: Fibroglycan (FG) is a major heparan sulfate proteoglycan (HSPG) in the rat liver that is mainly distributed on the surface of hepatocytes. HSPG may play some important roles in the regeneration of liver by interacting with various growth factors such as bFGF and HB-EGF. However, little is known about the function of FG. We reported that after injury caused by D-galactosamine, regeneration started on the following day and peaked on day 2. To clarify the function of FG in liver regeneration, we investigated the gene expression of FG during regeneration after D-galactosamine injury. MATERIALS AND METHODS: Rats were given D-galactosamine on day 0. Liver RNA was collected from day 0 to day 7. The gene expression of FG and beta-actin (as a representative cytoskeleton) was examined by Northern and/or Slot blotting. RESULTS: FG gene expression was markedly decreased on day 2, but totally recovered on day 3. In contrast, beta-actin gene expression was markedly increased on day 2 and returned to the normal level on day 3. Expression of the FG and beta-actin genes was reciprocal. CONCLUSION: FG expression is transiently suppressed when cytoskeleton gene expression is enhanced at the early phase of liver regeneration.

Actins↗

PubMedDate not supplied

Further characterization of negative regulatory element involved in the hormonal regulation of GlcNAc-1-P transferase gene in mouse mammary gland.

The gene encoding UDP-GlcNAc:dolichol phosphate N-acetylglucosamine-1-phosphate transferase (GPT), the enzyme that initiates the pathway for the biosynthesis of asparagine-linked glycoproteins, is ubiquitously expressed in eukaryotic cells. However, its expression in the mammary gland is developmentally and hormonally regulated; transcription of the mouse mammary GPT gene is stimulated by the lactogenic hormones, insulin, glucocorticoid, and prolactin. Earlier, we demonstrated that a distal negative regulatory element in mouse GPT (mGPT) promoter plays an important role in developmental and hormonal control of mGPT gene expression in mammary gland (Ma J, Saito H, Oka T and Vijay IK (1996) J Biol Chem, in press). In this report, a tissue distribution of the repressor that binds the negative regulatory element was examined; a comparison of the negative regulatory element to other consensus sequences for known transcription factors is discussed.

Animals↗

PubMedDate not supplied

Vascular endothelial growth factor enhances vascularization in microporous small caliber polyurethane grafts.

Neoarterial regeneration in an implanted small caliber vascular prosthesis is complexly controlled by many structural and biologic factors, such as cytokines. The authors designed an artificial graft, which was prepared as follows. Segmented polyurethane tubular film (inner diameter, 1.5 mm; wall thickness, 100 microns; length, 20 mm), in which micropores (pore size, 100 microns) were fabricated by an excimer laser ablation technique, were coated with a mixed solution of photoreactive gelatin and heparin with or without cytokines (vascular endothelial growth factor [VEGF]: 5 or 50 micrograms/ml, basic fibroblast growth factor [bFGF]: 1 microgram/ml). These coated grafts were irradiated by ultraviolet light, and were implanted in aortas of rats for 4 weeks; the VEGF (5 micrograms/ml) group, n = 6; the bFGF group, n = 6; the VEGF (5 micrograms/ml)/bFGF group, n = 11; the VEGF (50 micrograms/ml)/bFGF group, n = 5; and the control group, n = 9. Control grafts were treated without cytokines. Endothelial coverage was greater for the cytokine immobilized groups (approximately equal to 50-60%) than for the control group (approximately equal to 30%). At the midportion of the triple VEGF immobilized group, many capillaries were seen in the neoarterial intima, and in the micropores, although such capillaries were rarely observed in the bFGF and control groups. Thus, impregnation of VEGF in the gelatinous layer of grafts enhanced transanastomotic tissue ingrowth and transmural capillary ingrowth.

Animals↗

PubMedDate not supplied

A new double lumen balloon catheter for retrograde cerebral perfusion via jugular vein cannulation.

A new catheter for retrograde cerebral perfusion (RCP) was developed that can be used to deliver blood directly into the internal jugular vein (IJV) beyond the venous valves at the jugular-subclavian junction and prevent blood from draining into the lower half of the body. This catheter can be inserted into the IJV via a standard puncture technique by use of a 14 Fr sheath. The catheter shaft has two channels for balloon inflation and blood perfusion, respectively. A balloon for occlusion of drainage veins (superior vena cava and azygos vein) is installed at the catheter tip. Side holes, through which oxygenated cold blood is delivered into the IJV, are located 95 mm from the catheter tip. In a mock circulatory study, the pressure at the perfusion line (16-118 mmHg) increased with the increasing flow rate (0-400 ml/min). In clinical application, under circulatory arrest with profound hypothermia, inflation of the balloon effectively reduced blood drainage into the lower half of the body and, consequently, RCP was successfully performed (flow rate, 300-350 ml/min; pressure at the IJV, 15 mmHg). Because all of these procedures were controlled from outside the operative field, RCP by use of this catheter could be useful in distal arch replacement via left lateral thoracotomy.

Animals↗

PubMedDate not supplied

Tissue engineering of skeletal muscle. Highly dense, highly oriented hybrid muscular tissues biomimicking native tissues.

A highly dense, highly oriented hybrid muscular tissue was devised using C2C12 cells (skeletal muscle myoblast cell line) and Type I collagen. A cold mixture of C2C12 cells suspended in DMEM (Dulbecco's modified Eagle's medium; Gibco Lab Inc., Grand Island, NY) and Type I collagen solution was poured into capillary tube molds of two different sizes (inner diameters: 0.90 mm and 0.53 mm, respectively) sealed at each end. After centrifugation (1000 RPM, 5 min) and subsequent thermal gelation, a rod shaped gel was formed. The resultant gel shrank to become a highly dense tissue after incubation on an agarose gel coated dish. Small diameter rod shaped tissues were composed of numerous multi-nucleated myotubes and a few necrotic cells. On the other hand, a ring shaped tissue fabricated by centrifugation with a specially devised agarose gel mold was subjected to cyclic stretching at 60 RPM. The resultant highly dense, highly oriented hybrid muscular tissue involved both densely accumulated cells and collagen fiber bundles, which tended to be aligned in the direction of stretching. Sequential procedures of a centrifugal cell packing method and a mechanical stress loading method facilitated fabrication of hybrid muscular tissues similar to native muscular tissues in terms of cell density and orientation.

Animals↗

PubMedDate not supplied

Point mutations in the S and pre-S2 genes observed in two hepatitis B virus carriers positive for antibody to hepatitis B surface antigen.

Two hepatitis B virus (HBV) carriers who had antibodies to HBV surface antigen (anti-HBs) were studied. Case 1 was a 47 year old woman positive for hepatitis B e antigen (HBeAg), and case 2 was a 61 year old man positive for antibody to HBeAg (anti-HBe) and DNA-polymerase (DNA-p). Neither case had received the HBV vaccine. The nucleotide sequences of the HBV-DNA extracted from the patients' sera were determined within the pre-S2 and S genes. Seven out of nine S gene clones from case 1 and six out of nine S gene clones from case 2 had an amino acid replacement from Thr or Ile to Ser at codon 126 in the alpha-determinant of the S gene. Amino acid substitution of codon 145 of the S gene previously reported was not observed. Although two previous reports on HBV escape mutant carriers with both anti-HBs and HBeAg described some deletions in the pre-S2 gene, our cases did not show these deletions. Our analysis indicated that carriers with the HBV escape mutant did not always have pre-S2 gene deletions. We found two HBV escape mutant carriers who had amino acid substitutions at codon 126 in the S gene due to point mutation without any deletions in the pre-S2 gene.

DNA, Viral↗