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T Oka

Publications and source records attributed to T Oka.

At least 361 records · Page 20Linked to original sources

Micrometastatic P53-positive cells in the lymph nodes of non-small-cell lung cancer: prognostic significance.

OBJECTIVES: Approximately one fourth of all patients with stage I non-small-cell lung cancer die of tumor recurrence, despite radical removal of their tumors. We thus tried to detect micrometastasis in the regional lymph nodes indicated to be tumor free by conventional histopathologic methods in patients with non-small-cell lung cancer by using immunohistochemical staining for p53 protein. We also investigated the relation between micrometastatic p53-positive cells in the lymph nodes and the prognosis of the patients. METHODS: Samples from 480 regional lymph nodes were taken from 47 patients who underwent pulmonary resection for non-small-cell lung cancer and whose primary lesions were positive for p53 immunohistochemical staining. These samples were fixed in formalin and embedded in paraffin. We used p53 immunohistochemical staining to detect micrometastatic tumor cells in the lymph nodes. RESULTS: Cells positive for p53 protein were found in 14 of 31 (45%) patients with a negative pathologic lymph node status and in 26 of 315 (8.3%) lymph nodes in these patients. The proportion of patients with micrometastasis who survived was also significantly lower than the proportion of patients without micrometastasis who survived (p = 0.0001). CONCLUSIONS: Immunohistochemical staining for the p53 protein offers a rapid, sensitive, and useful way of detecting for micrometastasis to the regional lymph nodes in patients with non-small-cell lung cancer that is positive for p53 staining. The patients with such micrometastases have a poor prognosis and thus need to be carefully followed up after the initial pulmonary resection.

Carcinoma, Non-Small-Cell Lung↗

Glutamine and arginine metabolism in tumor-bearing rats receiving total parenteral nutrition.

Arginine supplementation increases glutamine levels in muscle and plasma. Since glutamine production is increased in catabolic states, these observations prompted us to investigate whether the flux of arginine to glutamine was increased in tumor-bearing (TB) rats, and we measured the synthesis rate of glutamine from arginine in control versus TB rats receiving standard total parenteral nutrition (TPN) solution. Male Donryu rats (N = 36; body weight, 200 to 225 g) were divided into two groups, control and TB rats. Yoshida sarcoma cells (1 x 10(6)) were inoculated into the back of the rats (n = 18) subcutaneously on day 0. The rats were given free access to water and rat chow. On day 5, all animals, including non-TB rats (n = 18), were catheterized at the jugular vein and TPN was begun. On day 10, TPN solution containing either U-14C-glutamine (2.0 microCi/h) or U-14C-arginine (2.0 microCi/h) was infused as a 6-hour constant infusion. At the end of the isotope infusion, plasma was collected to determine the glutamine production rate in rats receiving U-14C-glutamine, and the ratio of specific activity of glutamine to specific activity of arginine was measured in rats receiving U-14C-arginine. Only 2 g tumor caused a decrease in glutamine levels and an increase in glutamine and arginine production. The low flux rate of arginine to glutamine was observed in control rats (Arg to Gln, 41.0 +/- 11.9 mumol/kg/h). On the other hand, TB caused a significant increase in Arg to Gln compared with the control (213.3 +/- 66.1 mumol/kg/h, P < .01 v control). An increase in the flux rate of Arg to Gln was associated with an enhancement in the ratio of specific activity of ornithine to specific activity of arginine in TB rats (control 51.5% +/- 10.9% v 77.4% +/- 8.9%, P < .05). We conclude that (1) glutamine and arginine metabolism is altered with very small tumors, (2) although the flux of Arg to Gln was increased in TB and rats, the small increase in Arg to Gln cannot explain the observed large increase in Gln production.

Animals↗

Ruptured abdominal aorta secondary to psoas muscle abscess due to Klebsiella pneumoniae in an alcoholic.

An alcoholic patient with low back pain and Klebsiella pneumoniae septicaemia is reported. Computed tomography revealed abdominal aortic rupture associated with a psoas abscess. Aortic ligation above and below the rupture site and an axillo-femoral bypass were performed, but the patient died on the first postoperative day. Alcoholism is a common underlying disease in K. pneumoniae septicaemia and its septic metastasis to the psoas muscle. The prognosis of aortic infection secondary to psoas abscess is very poor once aortic rupture occurs. Prompt abscess drainage following correct diagnosis and arterial reconstruction before aortic rupture are mandatory.

Adult↗

Increased expression of vascular endothelial growth factor in human hepatocellular carcinoma.

BACKGROUND/AIMS: Angiogenesis is critical for the development and progression of solid tumors. The purpose of this study was to evaluate the possible role of vascular endothelial growth factor (which is considered to be one of the most important factors involved in tumor-associated angiogenesis), in human hepatocellular carcinoma. METHODS: Vascular endothelial growth factor gene and protein expression were analyzed by means of Northern hybridization and immunohistochemical methods in 5 hepatocellular carcinoma cell lines. Secretion of vascular endothelial growth factor was evaluated by immunoblotting of conditioned medium of these hepatocellular carcinoma cells. Further, we compared the level of vascular endothelial growth factor expression in hepatocellular carcinoma tissues along with that in surrounding tumor-free tissues obtained from 20 patients. We also analyzed mRNA expression of Flt-1, one of the vascular endothelial growth factor specific high-affinity receptors, in hepatocellular carcinoma cell lines. RESULTS: Northern hybridization analysis and immunohistochemistry revealed that all cultured hepatocellular carcinoma cells exhibited a high level of vascular endothelial growth factor mRNA. In addition, vascular endothelial growth factor secretion by Hep G2, one of the hepatocellular carcinoma cell lines, was shown by Western blot. In vivo, we observed vascular endothelial growth factor expression in both hepatocellular carcinoma and non-hepatocellular carcinoma tissues. However, in 12 of 20 cases, vascular endothelial growth factor mRNA levels were significantly up-regulated in hepatocellular carcinoma tissues. In the majority of cases (10 out of 12 cases) with abundant tumor vascularity, vascular endothelial growth factor mRNA up-regulation in hepatocellular carcinoma tissues was observed. We failed to detect Flt-1 mRNA expression in hepatocellular carcinoma cells. CONCLUSIONS: This study suggests that the possibility that hepatocellular carcinoma cells overexpress the vascular endothelial growth factor gene and protein. These findings support the hypothesis that vascular endothelial growth factor is one of the important factors involved in the angiogenesis of hepatocellular carcinoma, and may even be involved in the development and/or progression of hepatocellular carcinoma itself.

Adolescent↗

Antibody efficacy as a keen index to evaluate influenza vaccine effectiveness.

The efficacy of the influenza vaccine is often understimated, due to the dilution of the outcome by noninfluenzal illnesses. We thus explored the methodology to evaluate the effect of the inactivated influenza vaccine under the following strict conditions: an assessment of the effectiveness on clinical illness among healthy adults in a small-scale mixed epidemic during the 1991-1992 season. The vaccine antigens included were A/Yamagata/32/89 (H1N1), A/Beijing/352/89 (H3N2), and B/Bangkok/163/90. Two indices were analyzed: "vaccine efficacy", a comparison between the vaccinees and the nonvaccinees; and "antibody efficacy", a comparison between those with and those without a protective level of pre-epidemic hemagglutination-inhibition (HAI) antibody. The odds ratio (OR) and its 95% confidence interval (95% CI) was calculated by the logistic regression model. A decrease in the age-adjusted OR of vaccination was not statistically significant: 0.54 (95% CI: 0.19-1.53) corresponding to vaccine efficacy (1-OR) of 46% (-53% to 81%). Among the vaccinees, a significantly decreased OR in those with a higher titer to A/Beijing was observed: 0.14 (0.02-0.92) adjusted for the mutual effects of pre-epidemic antibodies to different vaccine antigens. The adjusted ORs thus calculated for A/Yamagata and B/Bangkok were not found to be statistically significant. The antibody efficacy (1-OR) was estimated to be 86% (8% to 98%) against illnesses related to A/Beijing-like viruses. The product of antibody efficacy (86%) and the proportion of those who achieved a protective level of antibody after vaccination (73% for A/Beijing strain) was 63%, which is theoretically equivalent to the vaccine efficacy. Thus, the antibody efficacy is considered to be an important index, while the vaccine efficacy against clinical illnesses is easily disturbed by extraneous factors in the field trials.

Adult↗

An immunogenicity and efficacy study of purified chick embryo cell culture rabies vaccine manufactured in Japan.

Purified chick embryo cell rabies vaccine manufactured by the Chemo-Sero-Therapeutic Institute(Kaketsuken) at Kumamoto, Japan (Kaketsuken) was submitted to an immunogenicity and efficacy study. 52 severely rabies exposed patients were treated with the conventional five doses intramuscular WHO approved ('Essen') postexposure schedule. This included the administration of 40 IU kg-1 of equine rabies immune globulin on Day 0. A control group of equally severely exposed subjects were treated with human diploid cell rabies vaccine manufactured by the Swiss Serum and Vaccine Institute as well as human rabies immune globulin. There were no deaths in either group in the more than 2 years follow-up period. Subjects treated with the chick embryo vaccine showed greater suppression of the neutralizing antibody response by the equine rabies immune globulin than those given the human diploid cell vaccine and human rabies immune globulin. A group of 20 less severely rabies exposed patients who received only the chick embryo vaccine without immune globulin all had antibody titers greater than the WHO minimal acceptable level on Day 14, 30, 90 and 180. Fourteen subjects among the severely exposed vaccine and immune globulin study group were given vaccine boosters on Day 180 because of low antibody titers. It is concluded that chick embryo rabies vaccine manufactured by Kaketsuken is an immunogenic and effective rabies vaccine, but that the potency of future batches must be increased to provide a greater safety margin.

Animals↗

Free D-aspartate and D-serine in the mammalian brain and periphery.

It has long been assumed that L-forms of amino acids exclusively constitute free amino acid pools in mammals. However, a variety of studies in the last decade has demonstrated that free D-aspartate and D-serine occur in mammals and may have important physiological function in mammals. Free D-serine is confined predominantly to the forebrain structure, and the distribution and development of D-serine correspond well with those of the N-methyl-D-aspartate (NMDA)-type excitatory amino acid receptor. As D-serine acts as a potent and selective agonist for the strychnine-insensitive glycine site of the NMDA receptor, it is proposed that D-serine is a potential candidate for an NMDA receptor-related glycine site agonist in mammalian brain. In contrast, widespread and transient emergence of a high concentration of free D-aspartate is observed in the brain and periphery. Since the periods of maximal emergence of D-aspartate in the brain and periphery occur during critical periods of morphological and functional maturation of the organs, D-aspartate could participate in the regulation of these regulation of these developmental processes of the organs. This review deals with the recent advances in the studies of presence of free D-aspartate and D-serine and their metabolic systems in mammals. Since D-aspartate and D-serine have been shown to potentiate NMDA receptor-mediated transmission through the glutamate binding site and the strychnine-insensitive glycine binding site, respectively, and have been utilized extensively as potent and selective tools to study the excitatory amino acid system in the brain, we shall discuss also the NMDA receptor and uptake system of D-amino acids.

Animals↗

Prostaglandin E receptor EP3 subtype is involved in thermal hyperalgesia through its actions in the preoptic hypothalamus and the diagonal band of Broca in rats.

The effects of microinjection of prostaglandin E2 (PGE2) (0.5 fg-500 pg/0.2 microl) into the medial part of the preoptic area (MPO) on nociception were studied using a hot-plate test in rats. The intraMPO microinjection of PGE2 only at non-pyrogenic doses (5-50 fg) reduced the paw-withdrawal latency, suggesting hyperalgesia. Maximal reduction was obtained 15 min after the injection of PGE2 at 50 fg. Subsequently, to determine which types of prostanoid receptors are involved in the hyperalgesic effect of PGE2 in the MPO, we administered PGE2 receptor agonists, i.e., 17-phenyl-omega-trinor PGE2 (an EP1 receptor agonist), butaprost (an EP2 receptor agonist) and M&B28767 (an EP3 receptor agonist) into the MPO and observed the nociceptive behavior. The intraMPO injection of M&B28767 (0.005 fg-50 pg), like that of PGE2, exhibited a U-shaped dose response characteristic, i.e., a significant decrease of the paw-withdrawal latency only at 0.05-5 fg with the maximal response at 0.5 fg. However, neither the administration of EP1 (0.5 fg-50 ng) nor EP2 (0.5 fg-500 pg) agonists had any effect on nociception. The microinjection of M&B28767 at 0.5 fg into the other parts of preoptic hypothalamus (the lateral part of the preoptic area and the median preoptic nucleus) and the diagonal band of Broca (DBB) produced hyperalgesia similar to the intraMPO-induced hyperalgesia in terms of magnitude and time course. Microinjection of M&B28767 (0.5 fg) into either the paraventricular nucleus, the ventromedial hypothalamus, the lateral hypothalamic area or the septal nucleus had no effect on nociception. These findings suggest that PGE2 at non-pyrogenic doses in the brain induces hyperalgesia, at least in part, through its actions on EP3 receptors in the preoptic hypothalamus and the DBB in rats.

Alprostadil↗

Initial MRI findings of non-traumatic osteonecrosis of the femoral head in renal allograft recipients.

Fifty-one renal allograft recipients (15-62 years old, mean: 37 years) were monitored for 2.5-6.5 years (average: 4.3 years) after surgery by using magnetic resonance imaging (MRI) to find (i) initial signs of osteonecrosis of the femoral head (ONF), (ii) the presence of bone marrow edema as an initial sign of ONF, (iii) any changes of MRI patterns, and (iv) the relationship between these MRI findings and prognosis. MRI was performed preoperatively (baseline), and whenever possible during the 6-9th week, 12-16th week, 12th month, and yearly thereafter. T1- and T2-weighted images were obtained by using a spin echo technique. Abnormalities were first detected on MRI of 23 femoral heads in 13 patients between 6 weeks and 12 months. All lesions first showed a low intensity band on T1-weighted images and a high intensity band on T2-weighted images. No symptoms or diffuse patterns, such as bone marrow edema, preceded the appearance of the band pattern. After the 12th month, no new abnormal findings on MRI were detected. The lesions were classified into Type A, B, or C, according to the location. 12 of the 16 Type C femoral head lesions, which extend beyond the medial two thirds of the weight-bearing portion of the acetabulum, became symptomatic 7-14 months after transplantation and then progressed to collapse. Bone marrow edema appeared with radiological collapse and symptoms. With the exception of five lesions in three patients who failed to be MR imaged until 12 months postoperatively, all lesions were first detected on MRI within 16 weeks after transplantation. We therefore postulate that the ischemic event that causes ONF will have occurred within 12 weeks after transplantation, considering the time lag of reparative reaction to the dead bone.

Adolescent↗

Bronchiolitis obliterans organizing pneumonia after syngeneic bone marrow transplantation for acute lymphoblastic leukemia.

We report a patient who developed bronchiolitis obliterans organizing pneumonia (BOOP) after syngeneic BMT for ALL. The patient complained of persistent low-grade fever and non-productive cough after engraftment. Chest CT scan showed patchy infiltration bilaterally in the lower lung fields. Antibiotics were ineffective. Cultures, serological studies and polymerase chain reaction detected no infectious pathogens. We finally made a diagnosis of BOOP by thoracoscopical lung biopsy. The lung lesion disappeared in a month with corticosteroid therapy. While BOOP following allogeneic BMT has been reported, this is the first report after syngeneic transplantation.

Adult↗

Vitamin B6 suppresses growth and expression of albumin gene in a human hepatoma cell line HepG2.

The effect of vitamin B6 on the growth of a human hepatoma cell line HepG2 in culture was studied. The growth of HepG2 cells and protein synthesis were almost completely inhibited in medium supplemented with 5 mM pyridoxine. Pyridoxal was as effective as pyridoxine, but pyridoxamine showed no inhibitory action. The growth inhibition of HepG2 cells by pyridoxine was accompanied by a marked inhibition of secretion of plasma proteins, particularly albumin. Northern blot analysis of albumin mRNA showed that pyridoxine caused a rapid decrease in the expression of albumin gene. The electron-microscopic examination of pyridoxine-treated HepG2 cells revealed a smoothing of nuclear membrane, a decrease in the number of nucleoli, and an appearance of aggregated heterochromatin structures. These morphological features are compatible with the depressed transcriptional activity in the pyridoxine-treated cells. The mechanism by which vitamin B6 exerts its inhibitory effect was discussed in terms of our recent finding that vitamin B6 modulates expression of albumin gene by inactivating tissue-specific DNA-binding proteins. Binding of pyridoxal phosphate with tissue-specific transcription factors may reduce the capacity of these factors to interact with the regulatory region of albumin gene, resulting in the inhibition of the gene expression.

Blotting, Northern↗

Caenorhabditis elegans cDNA for a Menkes/Wilson disease gene homologue and its function in a yeast CCC2 gene deletion mutant.

The full-length cDNA coding for a putative copper transporting P-type ATPase (Cu2+-ATPase) was cloned from Caenorhabditis elegans. The putative Cu2+-ATPase is a 1,238-amino acid protein, and highly homologous to the Menkes and Wilson disease gene products mutations of which are responsible for human defects of copper metabolism. The Saccharomyces cerevisiae mutant with a disrupted CCC2 gene (yeast Menkes/Wilson disease gene homologue) was rescued by the cDNA for the C. elegans Cu2+-ATPase but not by the cDNA with an Asp-786 (an invariant phosphorylation site) to Asn mutation, suggesting that the C. elegans Cu2+-ATPase functions as a copper transporter in yeast. The expressed C. elegans protein was detected in yeast vacuolar membranes by immunofluorescence microscopy. The yeast expression system may facilitate further studies on copper transporting P-type ATPases.

Amino Acid Sequence↗

152Eu depth profiles in granite and concrete cores exposed to the Hiroshima atomic bomb.

Two granite and two concrete core samples were obtained within 500 m from the hypocenter of the Hiroshima atomic bomb, and the depth profile of 152Eu was measured to evaluate the incident neutron spectrum. The granite cores were obtained from a pillar of the Motoyasu Bridge located 101 m from the hypocenter and from a granite rock in the Shirakami Shrine (379 m); the concrete cores were obtained from a gate in the Gokoku Shrine (398 m) and from a pillar top of the Hiroshima bank (250 m). The profiles of the specific activities of the cores were measured to a depth of 40 cm from the surface using low background germanium (Ge) spectrometers. According to the measured depth profiles, relaxation lengths of incident neutrons were derived as 13.6 cm for Motoyasu Bridge pillar (granite), 12.2 cm for Shirakami Shrine core (granite), and 9.6 cm for concrete cores of Gokoku Shrine and Hiroshima Bank. In addition, a comparison of the granite cores in Hiroshima showed good agreement with Nagasaki data. Present results indicates that the depth profile of 152Eu reflects incident neutrons not so high but in the epithermal region.

Biophysics↗

Dedifferentiated chondrosarcoma of the rib with a malignant mesenchymomatous component: an autopsy case report.

A rare variant of dedifferentiated chondrosarcoma with malignant mesenchymomatous component in a 57-year-old male is reported. The patient presented with a posterior mediastinal mass arising from the left eighth and ninth ribs showing well differentiated, low-grade chondrosarcoma. Five years later, local recurrence occurred and an excised specimen also showed the same histological features as the primary tumor. Another 6 years later, the tumor recurred and metastasized to the multiple organs, the patient dying 4 months later. Autopsy revealed that the recurrent and metastatic tumors showed malignant mesenchymomatous 'dedifferentiation' of chondrosarcoma composed of rhabdomyosarcoma, angiosarcoma, chondrosarcoma, osteosarcoma, and leiomyosarcoma, in addition to fibrosarcomatous areas. Although the less differentiated component of dedifferentiated chondrosarcoma usually shows the histological features of malignant fibrous histiocytoma and fibrosarcoma, multilineage differentiation can occur in that component. The phenomenon of 'dedifferentiation' in chondrosarcoma and the relationship to and distinction from malignant mesenchymoma of soft tissue and bone are discussed.

Autopsy↗

X-ray diffraction studies of bacteriorhodopsin. Determination of the positions of mercury label at several engineered cysteine residues.

The single cysteine-containing bacteriorhodopsin mutants F27C, L100C, T170C, F171C and I222C were labeled with p-chloromercuribenzoic acid, which specifically reacts with sulfhydryl groups. These cysteines should be located at the cytoplasmic ends of the transmembrane helices A, C, F or G. We determined the positions of the bound mercury atoms by X-ray diffraction of purple membrane films, with better than 1 A accuracy. The determined mercury positions were compared with the structural model from cryoelectron microscopy (N. Grigorieff, T. A. Ceska, K. H. Downing, J. M. Baldwin and R. Henderson, J. Mol. Biol. 259, 393-421, 1996). Given that the distance between the mercury and the C alpha atom of the cysteine in the xy plane must be shorter than 4.5 A and that the mercury atom is located at the delta position, the positions obtained for the mercury labels agree with their expected positions from the structural model. The present results give a rationale for detecting structural changes upon illumination as shifts occur in the mercury label position.

Amino Acid Sequence↗

[Effect of the prior influenza vaccination on serum antibody titer induction by subsequent inactivated influenza vaccine in the elderly].

In order to investigate the effects of prior influenza vaccination on subaequent annual influenza vaccination in the geriatric population, we analyzed serum hemagglutinine inhibition antibody tirers (HI titer) before and after vaccination with inactivated influenza vaccine in elderly inpatients. A total of 163 inpatients of 60 years or older were enrolled with informed consent. They were classified by vaccination status in the previous year, 53 patients had inactivated vaccine (inactivated). 52 patients had genetically assorted cold-adapted influenza live attenuated vaccine (cold-adapted), and 53 had no influenza vaccine history during the past year. The HI titer was higher in the inactivated group than in the cold-adapted and non-vaccinated groups, suggesting residual immunological effects of inactivated influenza vaccine from the previous year vaccination. The HI titer after the inactivated vaccine in 1993 was higher in both the inactivated and cold-adapted groups than in the non-vaccinated group. The number of patients with HI titers of 2(7) or higher, which is the putative protective HI titer level for influenza infection, was significantly higher in both the inactivated and cold-adapted groups than the non-vaccinated group. These results suggest that continuous annual influenza vaccination does not impair the effects of vaccination, and may actively promote elevated HI titers.

Aged↗