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T Oka

Publications and source records attributed to T Oka.

At least 1,495 records · Page 83Linked to original sources

Expression cloning and signal transduction pathway of P2U receptor in mammary tumor cells.

Extracellularly applied ATP, UTP and UDP induce a transient increase in the intracellular Ca2+ concentration of mammary cells via a P2U receptor. The P2U receptor in the mammary tumor cell line MMT060562 was cloned and expressed in the human leukemia cell line K-562. The deduced amino acid sequence of the mammary tumor cell P2U receptor was 98% homologous with that of mouse NG108-15 cells. It was a member of the superfamily of GTP-binding-protein-coupled receptors. ATP and UTP induced the increase in the intracellular concentrations of Ca2+ and inositol-1,4,5-trisphosphate in both mammary tumor cells and P2U-receptor-expressed K562 cells. Dose-response curves on the production of inositol-1,4,5-trisphosphate and Ca2+ by ATP and UTP were consistently similar. Injection of GTP enhanced the ATP-induced outward current and injection of GTP gamma S induced a repetitive outward current. Both pertussis and cholera toxins did not affect ATP-induced calcium increase. It was suggested that the P2U receptor coupled with pertussis- and cholera-toxin-insensitive GTP-binding proteins and activated phosphoinositide turnover.

Adenosine Diphosphate Ribose↗

Effect of arginine-enriched total parenteral nutrition on the host-tumor interaction in cancer-bearing rats.

By using a transplantable Yoshida sarcoma in a rat total parenteral nutrition model, we measured the effectiveness of an arginine-enriched amino acid solution (AI-82) in terms of leucine kinetics and nitrogen balance as indicators of host-tumor nutrition interaction compared with that of a conventional amino acid solution (Proteamin12). When tumor-bearing rats received isocaloric total parenteral nutrition solutions for 7 days, AI-82 significantly improved host nitrogen balance and significantly decreased the tumor-nitrogen trap throughout the experimental period. Leucine kinetics of whole body and tissues were also determined by a 4-hour continuous infusion of each total parenteral nutrition solution containing 14C-leucine. Significantly increased whole-body leucine oxidation (p < .01) without an increase in leucine release from normal tissues was observed in the AI-82 group. Total incorporation of 14C-leucine into whole muscle was significantly elevated (p < .05) without changes in muscle protein degradation in the AI-82 group. In the whole tumor, AI-82 tended to decrease total incorporation of 14C-leucine, but there was no difference in leucine release caused by protein breakdown between the two groups. These findings suggest that AI-82 can improve the nutritional status of the host over that of the tumor.

Animals↗

Arginine-enriched solution induces a marked increase in muscle glutamine concentration and enhances muscle protein synthesis in tumor-bearing rats.

Using a transplantable Yoshida sarcoma in a rat model of total parenteral nutrition (TPN), we measured the effectiveness of an arginine-enriched amino acid solution (AI-82) on muscle glutamine concentration and muscle protein synthesis compared with that of a conventional amino acid solution (Proteamin12). After tumor-bearing rats had been given one of two isocaloric TPN regimens for 6 days, [15N]glycine (99 atom %) containing TPN solution was infused into animals at a constant rate of 8 mg of [15N]glycine per hour for 18 hours, after which the liver, skeletal muscle (gastrocnemius muscle), and tumor protein synthesis rates were measured. A significantly increased whole muscle protein synthesis rate was observed in the AI-82 group; there was no difference in the whole liver and tumor protein synthesis rates between the two groups. When each TPN solution was administered for 1 week, muscle concentrations of arginine, ornithine, glutamine, and glutamate were considerably higher in the AI-82 group than in the Proteamin12 group, and these differences were also accompanied by a decrease in the plasma branched-chain amino acid (BCAA) (leucine, isoleucine, and valine) levels in the AI-82 group. The high levels of muscle glutamine concentration in the AI-82 group were investigated in connection with the high use of exogenous branched-chain amino acids.

Amino Acids, Branched-Chain↗

Significance of nucleosides and a nucleotide mixture infusion on hepatic energy metabolism of 70% hepatectomized rabbits in postoperative phase.

BACKGROUND: The influence of administration of a nucleoside-nucleotide mixture on hepatic energy metabolism was investigated in 70% hepatectomized rabbits from 48 to 72 hours after hepatectomy. METHODS: From 48 to 72 hours after hepatectomy, animals underwent continuous i.v. infusion of 2 mL/kg body weight/h of 9 g/L NaCl (group S), 5.99 mmol/L nucleoside-nucleotide mixture (group N1) or 11.98 mmol/L nucleoside-nucleotide mixture (group N2). RESULTS: At 72 hours, there was no significant difference in the hepatic adenylate energy charge among groups (S, 0.84 +/- 0.01; N1, 0.82 +/- 0.02; N2, 0.85 +/- 0.01). The hepatic mitochondrial phosphorylation rate was 66.9 +/- 2.5, 76.3 +/- 11.1, and 108.4 +/- 14.1 nmol ATP/mg mitochondrial protein/min in groups S, N1, and N2, respectively. The value of group N2 was significantly higher than the value of group S (p < .01). In addition, DNA concentration of the remnant liver was 2.27 +/- 0.07, 2.56 +/- 0.17, and 3.19 +/- 0.42 mg/g wet liver in groups S, N1, and N2, respectively, showing a significant increase in group N2 compared with group S (p < .05). CONCLUSION: A continuous i.v. infusion of a nucleoside-nucleotide mixture to 70% hepatectomized rabbits from 48 to 72 hours after hepatectomy prolonged an enhancement of the hepatic mitochondrial phosphorylation rate and elevated DNA content of the remnant liver.

Adenine Nucleotides↗

Insulin-like growth factor 1 has beneficial effects, whereas growth hormone has limited effects on postoperative protein metabolism, gut integrity, and splenic weight in rats with chronic mild liver injury.

BACKGROUND: Both growth hormone (GH) and insulin-like growth factor 1 (IGF-1) improve protein metabolism after surgical insult in subjects without liver disease. However, these effects in chronic liver injury, in which the GH-IGF-1 axis is impaired, have not been investigated. We examined the anabolic effects of GH and IGF-1 after gastrectomy in rats with chronic mild liver injury. METHODS: Rats with chronic mild liver injury induced by thioacetamide were used. After gastrectomy, the rats were randomized into vehicle control, GH, and IGF-1 groups. In the latter two groups, 0.8 IU/kg/d of GH or 4 mg/kg/d of IGF-1 was infused for 72 hours. Anabolic effects were assessed by body weight change, 3-methylhistidine (3-MH) excretion, nitrogen excretion, and whole-body protein turnover. Organ weights, plasma levels of glucose, insulin, and IGF-1, tissue IGF-1 levels, hepatic messenger RNA (mRNA) content, and intestinal structure were also determined. RESULTS: Both GH and IGF-1 decreased nitrogen excretion. IGF-1, but not GH, increased postoperative body weight, whole-body protein turnover, and splenic weight. IGF-1 reduced atrophy of the intestinal mucosa. GH treatment increased hepatic IGF-1-mRNA and the plasma IGF-1 level, whereas IGF-1 treatment increased the plasma IGF-1 level with no change in the hepatic IGF-1-mRNA content. There were no significant differences in plasma glucose or insulin levels among the three groups. Neither GH nor IGF-1 affected the gastrocnemius muscle IGF-1 level. CONCLUSIONS: IGF-1 has beneficial effects, whereas GH has only limited effects on post-operative protein metabolism, gut integrity, and splenic weight in chronic mild liver injury.

Animals↗

Overview of clinical studies of childhood acute lymphoblastic leukemia for more than ten years by the Japanese Children's Cancer and Leukemia Study Group.

Since 1981, the Children's Cancer and Leukemia Study Group (CCLSG) has developed a series of protocols for treatment of acute lymphoblastic leukemia (ALL) in childhood. In the first randomized controlled study of the 811 protocol (1981-1983) a comparison of conventional daily 6-mercaptopurine and methotrexate with a pulsed regimen of the two drugs was performed. The superiority of the pulsed regimen was shown. In the next 841 protocol (1984-1987) a comparison of two drugs and three drugs during induction therapy was conducted. The three-drug regimen resulted in a significantly higher event-free survival (EFS) rate. In the 874 protocol (1987-1990) two regimens with or without cranial irradiation were randomly compared, and there was no significant difference between the two regimens for the standard-risk group. To further improve the EFS rate a risk group-directed protocol 911 was conducted starting in January 1991. Life-table analysis of serial CCLSG protocols revealed that the outcome of overall ALL has gradually improved with an increase of the EFS rate; 41.4% +/- 3.6% at 14 years for the 811 protocol, 51.3% +/- 3.5% at 11 years for the 841 protocol, 56.7% +/- 3.1% at 8 years for the 874 protocol, and 78.2% +/- 3.1% at 4 years for the more recent 911 protocol.

Antineoplastic Combined Chemotherapy Protocols↗

Efficacy of perioperative portal venous inoculation with donor lymphocytes on skin graft survivals in the rat.

Although the administration of donor lymphocytes via portal vein (PV) on the day of transplantation significantly prolongs rat renal allograft survivals and the unresponsive state is mediated by an antigen-specific suppressor factor in the serum, significant variations exist among rodent models in terms of immunogenicity and mechanism of antigen presentation. The present studies sought to assess the effect of perioperative PV inoculation with donor lymphocytes on skin allograft survivals. Donor lymphocytes were prepared from Brown-Norway (BN, RT-1n) or third-party DA (RT-1a) rat spleens and lymph nodes and injected via PV or intravenously to Lewis (LEW, RT-1l) hosts on the day of skin grafting. Untreated LEW hosts rejected BN skin grafts at 9.0 +/- 1.4 days (n = 10). Intravenous administration of 1 x 10(8) BN cells into LEW hosts on day 0 did not prolong the skin graft survivals (MST = 8.6 +/- 1.2 days, n = 7, NS), whereas PV inoculation of 1 x 10(8) BN cells prolonged skin graft survival to 13.4 +/- 3.9 (n = 8, P < .01). PV administration of 1 x 10(8) DA cells to LEW hosts did not prolong the survival of BN skin grafts (MST = 8.6 +/- 1.5 days, n = 6). PV inoculation with BN cells inhibited the generation of anti-BN delayed-type hypersensitivity (DTH) response in the hosts, whereas untreated control hosts or hosts inoculated with third-party DA cells could not inhibit the anti-BN DTH response.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Primary melanocytoma arising from the thoracic leptomeninges case.

Primary melanocytoma arising from the leptomeninges of the spinal cord is very rare. A surgical specimen of a thoracic meningeal tumor was resected from a 75-year-old woman complaining of gait disturbance was investigated. Magnetic resonance imaging and myelography showed a dumb-bell-type tumor in the subdural space at the 1st to 2nd thoracic vertebrae. The tumor was subtotally resected because of adhesion to the lamina and thoracic medulla. The localized, gelatinous black tumor showed a well-defined margin without dissemination or infiltration. The tumor had a thin capsule and was composed of solid proliferation of neoplastic melanocytes. Neither whorl formation nor foci of palisaded nuclei were observed. The neoplastic cells were of two major types: an epithelioid- or polygonal-shaped type and a spindle-shaped type, and had a large nucleus, a prominent nucleolus, coarse chromatin, and melanin-pigments in their cytoplasm. Only a few mitotic figures were observed. They were positive for HMB-45 and S-100 protein. This case was considered to be primary melanocytoma arising from the thoracic leptomeninges.

Aged↗

Esophagogastrostomy reconstruction after limited proximal gastrectomy.

BACKGROUND/AIMS: Recent advances in diagnostic techniques have led to the detection of an increasing number of early gastric cancers in the upper third of the stomach. The objective of this study was to determine the most appropriate surgical treatment for these cancers. METHODOLOGY: The clinicopathologic characteristics of 35 patients with early gastric cancer in the upper third of the stomach who underwent three different types of gastrectomies were reviewed retrospectively from hospital records between January 1992 and August 1999. RESULTS: Patients undergoing limited proximal gastrectomy with esophagogastrostomy reconstruction had shorter operation times and less blood loss than those for patients undergoing total gastrectomy or proximal gastrectomy with jejunal interposition. No lymph node metastasis was identified in any of these patients. Heartburn due to reflux esophagitis was seen in a few patients of each group, but they were successfully treated by antacids. The extreme reduction in food intake volume was more frequently experienced in patients with total gastrectomy than those with both proximal gastrectomies. When mortality due to other disease was excluded, all patients survived without recurrence. CONCLUSIONS: A limited proximal gastrectomy with esophagogastrostomy reconstruction decreased surgical risk and realized preservation of maximal function.

Esophagostomy↗

Control of cellular orientation in two-dimensional tissue formation. Surface topologic effect of collagen fibers on endothelialization.

The authors studied the effect of polymorphous states of collagen on in vitro cellular orientation of bovine aortic endothelial cells (ECs). Little orientation of adherent ECs was observed on a nonoriented collagen coated surface, irrespective of culture period. Only ECs that adhered to fiber bundles 10 microns in diameter exhibited cellular elongation or alignment. The collagen membrane with highly oriented fine fibers provided no cellular alignment for ECs in sparse culture. Resultant confluent monolayers, however, were characterized by cellular orientation, suggesting that surface microtopology of collagen induces cellular orientation on incubation. Control of cellular orientation would be an elementary requirement for cell seeding technology leading to hybrid artificial organs.

Animals↗

Experimental study on limitations of anastomotic endothelialization of vascular prostheses.

We studied the effect of endothelial cell (EC) senescence on proliferation, migration, and endothelialization in vitro using a culture model. Two generations of cultured bovine aortic ECs were used. The results showed that 1) the senescent ECs had much reduced rates of proliferation, migration, and endothelialization in vitro, and 2) that the young ECs at the leading edge gradually developed morphology similar to that of the senescent ECs as endothelialization proceeded. Computerized videomicroscopic observation revealed that the ECs at the leading edge had higher motile activity than the ECs at the back. This suggests that the ECs at the leading edge, and circumvented from contact inhibition, may proliferate much more frequently than the ECs at the back. Localized cellular aging may result in decelerated or incomplete endothelialization, as found clinically.

Anastomosis, Surgical↗

New assist method for orthotopic heart transplantation in the dog.

We used cross circulation as an assist method for orthotopic heart transplantation in eight dogs. Seven of the eight dogs could be extubated on the first to third postoperative day and were able to eat and walk several hours after extubation. The survival times and the causes of death in these eight dogs were as follows: 436 days (alive), 5 days (sudden death), 17 days (rejection), 17 days (pyothorax), 3 days (accidental death), 59 days (rejection), 19 days (pneumothorax), and 188 days (alive). None of the dogs died of any problems related to the use of cross circulation. Hematologic and biochemical studies revealed that the CK, CK-MB, LDH, GOT, GPT, and lactate levels increased shortly after the operation and returned to the preoperative values within 14 days. The blood urea nitrogen, creatinine, amylase, hematocrit, and total protein levels remained almost unchanged. No free hemoglobin was detected. These findings indicated that no severe damage occurred to the recipient's organs. The key factors for performing successful cross circulation are as follows: (1) The body weight of the support dog should be at least three times that of the recipient. (2) The systolic pressure of the support dog and the pressure gradient between the support and the recipient should be kept above 150 mm Hg and 50 mm Hg, respectively. (3) The flow rate in the arterial tube should be maintained at between 30% and 50% of the basal cardiac output of the recipient. In conclusion, cross circulation is a suitable assist method for orthotopic heart transplantation in the dog.

Animals↗

In vitro model of endothelialization at anastomotic sites.

Endothelial cell (EC) migration from native arteries to vascular prostheses is one of the most important healing processes of implanted artificial grafts, which results in endothelial cell coverage of the luminal surface of the graft. This article presents an in vitro model of endothelialization at the anastomotic site, which can provide cellular level information on morphologic reconstruction, and its substrate dependency. Test materials included polyethylene terephthalate (PET), segmented polyurethanes (SPUs), and glass with or without protein precoating (collagen, fibronectin, and albumin). In vitro endothelialization on these substrates was quantitatively determined by phase contrast microscopy. The results obtained show: 1) The fastest endothelialization rate was found on PET, followed by relatively hydrophobic SPU, and glass--the slowest was on hydrophilic SPU; and 2) Precoating with proteins drastically altered the cellular behaviors; collagen greatly enhanced endothelialization in vitro, followed by fibronectin. Precoating by albumin, however, greatly retarded endothelialization. The present study strongly suggests that unidirectional endothelialization at the anastomotic sites is controlled by the surface characteristics of graft materials.

Anastomosis, Surgical↗

Endothelialization on various segmented polyurethanes: cellular behavior and its substrate dependency.

Endothelialization on artificial substrates is essential for providing vital function to artificial and hybrid vascular prostheses. The authors studied fundamental behaviors of endothelial cells (EC), including adhesion, spreading, migration, and growth, on various segmented polyurethanes (SPU) with a wide variety of wettability. Endothelialization has a synergistic action on these cellular behaviors that was quantitatively evaluated by phase contrast microscopy. Surface characteristics of SPU were analyzed by contact angle measurement and X-ray photoelectron spectroscopy. Adhesion, spreading, migration, growth, and endothelialization in vitro of bovine aortic EC on relatively hydrophobic SPU exceeded those on both a hydrophilic SPU, and a very hydrophobic siliconized one. Minimal interaction with EC was found for hydrophilic SPU. Adherent cells tended to be delaminated from siliconized SPU in a later culture period. The addition of a peptidyl antagonist of adhesive protein receptor inhibited adhesion of EC on SPU. These results suggest that surface characteristics, possibly regulating adsorption of adhesive proteins, are important factors in the development of vascular SPU prostheses.

Animals↗

The possibility of improving biocompatibility by removing anaphylatoxins from the circuit of blood-perfused artificial organs.

The possibility of reducing bioreactivity during extracorporeal circulation by removing bioactive substances "turned on" in the devices is described in this paper. The bioreaction and bioactive products, as represented by neutrophil reaction and activated complement fragments generated during the use of a blood-perfused artificial organ, were studied as a model. Hemoperfusion with activated charcoal (AC) was used to remove the activated complement fragments. The adsorption of anaphylatoxins (C3a, C4a, and C5a) was evaluated following plasma perfusion through AC in vitro, all three of which were satisfactorily adsorbed. Six kinds of AC (three HEMA coated AC, two uncoated AC, and one cellulose coated AC) were compared with respect to adsorption of C5a in vitro. Uncoated AC adsorbed well and rapidly, but the coating with HEMA made adsorption take place slowly. The cellulose coating activated complement and did not decrease plasma C5a levels. After the adsorption of anaphylatoxins was confirmed, each of the AC columns was placed on-line after a cuprophan dialyzer in five chronic hemodialysis patients. C3a levels and neutrophil counts were compared with those obtained during usual hemodialysis (HD). By using heparin treated, uncoated AC, elevation of C3a levels and transient neutropenia were suppressed. Peak C3a with AC was reduced by 150% compared with prevalues, and the neutropenia nadir increased from 20% to 40% of baseline. The adsorption ability influenced the reduction in neutropenia. The heparinized uncoated AC and the column with large volumes of HEMA-coated AC had the best effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Anaphylatoxins↗

Reduction of the antigenicity and immunogenicity of xenografts by a new cross-linking reagent.

To overcome the disadvantages of glutaraldehyde (GA), new cross-linking reagents, polyepoxy compounds (PC), were introduced and their effects on the antigenicity and immunogenicity of biomaterials were investigated. In the qualitative study, antigenicity of type I collagen in bovine arteries treated with GA or glycerol polyglycidyl ether (GPE), a kind of PC, was detected using a fluorescent antibody technique. To evaluate the immunogenicity quantitatively, DDY mice were twice immunized with homogenates of GA, GPE, or untreated dog arteries. Using their sera collected 10 and 90 days after the last immunization as primary antibodies, the dogs' peripheral lymphocytes were stained with FITC labeled anti-mouse IgG antibodies against shared antigens on arteries and lymphocytes. Percentages of stained lymphocytes were then analyzed with flow cytofluorometry. In both qualitative and quantitative studies, extremely low antigenicity and immunogenicity were shown in GA or GPE treated arteries. It is therefore suggested that GPE is an ideal cross-linking reagent for vascular and valvular xenografts and is applicable to clinical use.

Animals↗

Development of an autologous connective tissue tube as a small caliber vascular substitute.

A small-caliber vascular graft with good healing properties was developed using an autologous connective tissue tube (ACTT) and in situ heparinization. ACTT is the best material for implantable grafts, but as a small-caliber vascular graft, both the high thrombogenicity and requirement for time to preparation in situ were serious problems. To overcome these difficulties, an ultrafine polyester fiber (UFPF) mesh was used for the framework of the graft. it has been shown that UFPF provides a good framework for fibroblast migration and proliferation both in vivo and in vitro. The granulomatous connective tissue tube could be constructed very rapidly and had numerous capillary blood vessels, which opened onto the luminal surface of the graft when it was implanted as a vascular substitute and provided colonies of endothelial cells. These colonies spread rapidly all over the luminal surface, and the graft developed permanent antithrombogenicity by endothelialization. The next problem was attainment of temporary antithrombogenicity of the graft before complete endothelialization. Since collagen fibrils are highly thrombogenic, the fact that ACTT collagen fibrils face the luminal surface requires greater antithrombogenicity. A new technique for binding heparin to collagen fibrils in situ was also developed. This was proved to be useful in maintaining the antithrombogenicity of the grafts (3 mm in inner diameter, 6 to 7 cm in length) in the animal studies. The graft showed rapid healing of the neonintima with endothelialization and long-term stability of the graft wall.

Angiography↗