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Biomedical subjects

T Matsuno

Publications and source records attributed to T Matsuno.

At least 19 recordsLinked to original sources

Glutaminase and glutamine synthetase activities in human cirrhotic liver and hepatocellular carcinoma.

Glutamine synthetase and glutaminase activities in human cirrhotic liver tissues and hepatocellular carcinomas were determined for comparison with normal liver tissues. In hepatocellular carcinoma, glutamine synthetase activity was approximately one-third of that in normal liver, whereas no detectable change in the enzyme activity was observed in cirrhotic liver. Phosphate-dependent and phosphate-independent glutaminase activities were increased approximately 20-fold and 6-fold, respectively, both in the carcinoma and cirrhotic liver compared with those from normal liver, Oxypolarographic tests showed that the rate of glutamine oxidation in the tumor and cirrhotic liver mitochondria was about 5-fold higher than that in the liver mitochondria. The rate of glutamate oxidation in the liver mitochondria was comparable to that in the cirrhotic liver and tumor mitochondria. Glutamine oxidation was inhibited by prior incubation of the mitochondria with 6-diazo-5-oxo-L-norleucine, which inhibited mitochondrial glutaminase. These results indicate that the product of glutamine hydrolysis, glutamate, is catabolized in the tumor and cirrhotic liver mitochondria to supply ATP. In the liver and cirrhotic liver mitochondria, glutamate was oxidized via the routes of transamination and deamination. On the other hand, glutamate oxidation was initiated preferentially via a transamination pathway in the tumor mitochondria.

Carcinoma, Hepatocellular

Oxidation of cytosolic NADH by the malate-aspartate shuttle in HuH13 human hepatoma cells.

1. The reoxidation of cytosolic NADH was studied in a line of human hepatoma cells (HuH13) whose mitochondria preferentially utilized glutamine for ATP formation. 2. The tumor cells showed mitochondrial reoxidation of NADH, as evidenced by the accumulation of pyruvate, when incubated aerobically with L-lactate. The involvement of the respiratory chain was demonstrated by the addition of specific inhibitors. 3. Glutamine oxidation proceeded in the tumor mitochondria exclusively via a pathway involving transamination. Malate stimulated aspartate production from glutamine. 4. When the tumor cells were cultured in Eagle's medium with aminooxyacetate or in the absence of glutamine, a marked reduction in the cellular NAD/NADH ratio was observed. 5. These results indicate that the malate-aspartate shuttle was functioning in the tumor cells.

Aspartic Acid

Retinotectal projection after partial ablation of chick optic vesicles.

We excised the dorsal part of the optic vesicle of chick embryos at stages 13-14 (embryonic day 2). The remainder of the optic vesicle reoganized and developed a small eye. This study was undertaken to determine how locus specificity is kept within the reorganized retina. The projection pattern from the reorganized eyes was examined with HRP and DiI, a fluorescence axon tracer. Whole retinal fibers labeled with HRP were found on the medial half of the contralateral tectum, thus showing the lateral half of the tectum as being devoid of retinal fibers. DiI labeling revealed a detailed projection map, with the dorsoposterior to ventroanterior axis of the reorganized eye being projected as the rostrocaudal axis on the medial half of the tectum. These results suggest that the positional specificity along the anteroposterior axis of the optic vesicle was already determined at the time of excision, and that the ventral part of the optic vesicle reorganized the "whole" retina, keeping its original anteroposterior polarity.

Animals

Effect of local hyperthermia and chemotherapy on MC29 virus-induced liver tumor transplanted into subcutis of chickens.

1. A transplantable liver tumor induced by MC29 virus, whose specific utilization of glutamine in growth of the tumor had been well-demonstrated, was implanted in the subcutis of day-old chickens, and after 7-8 days, when the tumor had reached a soybean size, local hyperthermia with microwave and/or chemotherapy with 6-diazo-5-oxo-1-norleucine (DON), an inhibitor of glutamine metabolism, were given once a day for 7 days successively. 2. At the 7th day of experiment, the tumor growth ratio, expressed by mean +/- standard deviation was, in the tumor control group, 14.3 +/- 1.81; in DON group, 6.93 +/- 0.95; in local hyperthermia group, 3.24 +/- 2.25, and in DON+hyperthermia group, 0.61 +/- 0.57. 3. The body weight-gain ratio in the local hyperthermia group was evidently higher than that in the tumor control group. DON suppressed body weight gain most remarkably. 4. In the present transplantable tumor system, microwave local hyperthermia was more effective in tumor suppression and less hazardous to the host than our former whole-body hyperthermia.

Animals

Anti-neoplastic effect of halocynthiaxanthin, a metabolite of fucoxanthin.

We have reported that fucoxanthin, a natural carotenoid, inhibited the growth of human neuroblastoma GOTO cells. In the present study, we show that a metabolite of fucoxanthin, halocynthiaxanthin, which is isolated from sea squirt Halocynthia roretzi, has a more potent inhibitory effect. Halocynthiaxanthin (5 micrograms/ml) caused complete suppression of GOTO cell proliferation, whereas fucoxanthin reduced the growth rate by only 88.8% compared with the control, at day 2 after the drug treatment. Furthermore, halocynthiaxanthin also inhibited the growth of other human malignant tumor cells. Thus halocynthiaxanthin seems to be a promising anti-neoplastic agent.

Antineoplastic Agents

Inhibition of neutrophil priming and tyrosyl phosphorylation by cepharanthine, a nonsteroidal antiinflammatory drug.

Receptor-mediated superoxide (O2.-)-generation and tyrosyl phosphorylation of neutrophil proteins, such as 58, 65, 84, 108 and 115 kDa, were enhanced by priming cells with granulocyte colony stimulating factor (G-CSF) [Akimura, K. et al. Arch. Biochem. Biophys. 298: 703-709, 1992]. To elucidate the possible involvement of tyrosyl phosphorylation of neutrophil proteins in the enhancing mechanism of O2.- generation, the effect of cepharanthine, a biscoclaurine alkaloid that inhibits phorbol 12-myristate 13-acetate (PMA)- and receptor-mediated O2.- generation, on the priming of human peripheral neutrophils (HPPMN) was studied. Both enhancement of formyl-methionyl-leucyl- phenylalanine (FMLP)-mediated O2.- generation and tyrosyl phosphorylation of some neutrophil proteins, i.e., 115, 108 and 84 kDa proteins, by HHPMN after treatment with G-CSF were strongly inhibited by cepharanthine in a concentration- and treatment-time-dependent manner. In contrast, inhibition of PMA-mediated O2.- generation by cepharanthine was weak and independent of treatment time. These results suggest that cepharanthine might inhibit the priming step of neutrophil activation concomitantly with its inhibition of the tyrosyl phosphorylation of some neutrophil proteins that might underlie the mechanism for priming of neutrophils with G-CSF.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine

Renal transplantation from HLA-haploidentical living-related donors: the effects of donor-specific blood transfusions and different immunosuppressive regimens.

One-hundred-nine HLA-haploidentical living related renal transplants have been retrospectively analysed to compare the effect of donor-specific blood transfusion (DST) and different immunosuppressive regimens on graft survival and acute rejection. The recipients were divided into four groups according to the immunosuppressive therapy. Group 1 (n = 44): conventional therapy with posttransplant azathioprine (AZP) + methylprednisolone (MP). Group 2 (n = 25): pretransplant DST + posttransplant AZP + MP. Group 3 (n = 12): triple-drug therapy with posttransplant AZP + MP + cyclosporine (CS). Group 4 (n = 25): pretransplant DST + posttransplant AZP + MP + CS. The five-year actuarial survival rates for groups 1, 2, 3 and 4 were 48%, 73%, 79%, and 89%, respectively. The graft survival rate in group 3 was significantly (p less than 0.01) better than that in group 1. The transfusion effect was reduced, and appears as a 10% improvement in the graft survival in the cyclosporin era compared with a 25% improvement at pre-cyclosporin era. Furthermore, the incidence of the first rejection episode was decreased in recipients that received DST. The present study revealed that DST, as pretransplant conditioning has a definite impact on rejection-free long-term graft survival in HLA-haploidentical living-related kidney recipients and the most favorable outcome in such patients could be achieved by DST pretreatment in conjunction with posttransplant triple-drug therapy including cyclosporine.

Blood Transfusion

The impact of triple drug immunosuppression on clinical results of cadaveric kidney transplantation: a comparison of conventional immunosuppression.

A retrospective study was carried out in 110 cadaveric kidney transplant recipients to compare the effects of low doses of cyclosporine (CsA), azathioprine (AZP) and steroids (triple-drug therapy) with those of higher doses of steroids plus AZP (conventional immunosuppression). Graft survival rate in the triple-drug therapy was 77%, 69%, and 69% at 1, 3, and 5 years, respectively. This was significantly better than 48%, 34%, and 29% in conventional immunosuppression. The incidence of acute rejection episodes was significantly lower in the triple-drug therapy than in conventional immunosuppression (25% vs 58%). In conclusion, our study shows that triple-drug therapy using low-dose cyclosporine is the safest of the immunosuppressive regimens and provides a beneficial effect on the long-term survival of cadaveric kidney transplants.

Adult

Modified Chiari pelvic osteotomy: a long-term follow-up study.

In a series of 100 modified Chiari pelvic osteotomies in ninety-six patients, who were followed for an average of nine years and three months (range, six years to fourteen years and eight months), an excellent or good clinical result was obtained in seventy-eight hips. The level of the osteotomy line on postoperative radiographs was compared with the clinical result. The average clinical result was good in seventy-four (84 per cent) of the eighty-eight patients in whom the osteotomy was at the I-I, I-II, or II-II level, according to the classification of levels by Azuma et al., but was good in only four of the twelve patients in whom the osteotomy was at another level (p = 0.0003). We found that smooth anterior and lateral coverage can be obtained by the use of a dome-shaped osteotomy line.

Adolescent

Regulation of the rostrocaudal axis of the optic tectum: histological study after rostrocaudal rotation in quail-chick chimeras.

Transplantation of the quail tectum primordia after rotation of its rostrocaudal axis through 180 degrees into a chick embryo was carried out at around the 10-somite stage. Our previous study showed that the rostrocaudal specificity was not determined at the stage when the transplantation was carried out in view of the retinotectal map formation. Here, we report the cytoarchitectonic development of the rotated tectum by comparing it with the quail tectum development. In the quail and chick embryos, the rostral part of the tectum had a thicker wall and was in more advanced cytoarchitectonic differentiation than the caudal part. Such cytoarchitectonic gradient along the rostrocaudal axis of the tectum became discernible on day 5.5 of incubation (E5.5) in quail embryos. In the rotated tectum, the rostral part, though it was originally caudal, had a thicker wall and more advanced cytoarchitecture than the caudal part at E5.5 and E6.5. Our results suggest that the rostrocaudal gradient of the cytoarchitecture is regulated to that of the host by E5.5.

Animals

Pathway of glutamate oxidation and its regulation in the HuH13 line of human hepatoma cells.

Well-coupled mitochondria were isolated from a HuH13 line of human hepatoma cells and human liver tissue. The liver mitochondria showed a feeble glutamine oxidation activity in contrast to the hepatoma mitochondria, whereas they utilized glutamate well for the oxidative phosphorylation. In the liver mitochondria, glutamate was oxidized via the routes of transamination and deamination. On the other hand, glutamate oxidation was initiated preferentially via transamination pathway in the tumor mitochondria. In the liver mitochondria, bicarbonate nearly at a physiological concentration inhibited oxygen uptake with glutamate as substrate. The interaction of bicarbonate with the pathway of glutamate oxidation occurred primarily at the level of succinate dehydrogenase, due to competitive inhibition of the enzyme by the compound. In contrast to the liver mitochondria, glutamate oxidation was not affected by bicarbonate in the tumor mitochondria. These results indicate that the aberrations in the glutamate metabolism and its regulation observed in the hepatoma mitochondria may be favorable to the respiration utilizing glutamine and/or glutamate as an energy source.

Alanine Transaminase

Luminol chemiluminescence and active oxygen generation by activated neutrophils.

Upon stimulation by various ligands and membrane perturbers, neutrophils produce various active oxygen species. Since luminol chemiluminescence (LCL) in neutrophils can be blocked by azide, an inhibitor of myeloperoxidase, LCL has been believed to reflect mainly the myeloperoxidase-catalyzed reaction. When cells were stimulated by formyl-methionyl-leucyl-phenylalanine, LCL was strongly inhibited by superoxide dismutase (SOD) and uric acid, a scavenger for hydroxy radical (.OH) and singlet oxygen, whereas it was stimulated by azide. LCL was also inhibited by .OH scavengers, such as mannitol, ethanol, and dimethylsulfoxide. However, when stimulated by phorbol myristate acetate or opsonized zymosan, LCL was strongly inhibited by azide but not by uric acid, and the inhibitory action of SOD was low. Thus, the qualitative and quantitative aspects of reactive oxygen generation by activated neutrophils differ significantly from one ligand to another. These results suggest that the metabolic fate of active oxygens in neutrophils and, hence, their effect on microorganisms and the surrounding tissues might differ depending on the stimulus.

Animals