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Biomedical subjects

T Inoue

Publications and source records attributed to T Inoue.

At least 1,171 records · Page 65Linked to original sources
PubMed1996

Amorphization of Serpentine at High Pressure and High Temperature

Pressure-induced amorphization of serpentine was observed at temperatures of 200° to 300°C and pressures of 14 to 27 gigapascals with a combination of a multianvil apparatus and synchrotron radiation. High-pressure phases then crystallized rapidly when the temperature was increased to 400°C. These results suggest that amorphization of serpentine is an unlikely mechanism for generating deep-focus earthquakes, as the temperatures of subducting slabs are significantly higher than those of the rapid crystallization regime.

Journal Article↗
PubMed1996

Infection with hepatitis GB virus C in patients on maintenance hemodialysis.

BACKGROUND: A recently discovered non-A-E hepatitis virus has been designated hepatitis GB virus C (HGBV-C), but little is known about its mode of transmission and its clinical manifestations. We studied 519 patients on maintenance hemodialysis to determine whether they were infected with HGBV-C. METHODS: HGBV-C RNA was identified in serum by a reverse-transcription-polymerase-chain-reaction assay with nested primers deduced from a non-structural region. A nucleotide sequence of 100 bp in the nonstructural region was determined on HGBV-C clones. RESULTS: HGBV-C RNA was detected on 3.1 percent of the patients on hemodialysis (16 of 519), as compared with 0.9 percent of healthy blood donors (4 of 448, P<0.03). None of the 16 patients had evidence of active liver disease, although 7 were also infected with hepatitis C virus. Eight patients with HGBV-C infection were followed for 7 to 16 years. In two patients the virus was present at the start of hemodialysis. One had a history of transfusion, and HGBV-C persisted over a period of 16 years; the other became free of HGBV-C after 10 years. In five patients, HGBV-C RNA was first detected 3 to 20 weeks after blood transfusion and persisted for up to 13 years. One patient with no history of transfusion was infected with an HGBV-C variant with the same sequence as in two of the patients with post-transfusion HGBV-C infections. CONCLUSIONS: Patients on maintenance hemodialysis are at increased risk for HGBV-C infection. This virus produces persistent infections, which may be transmitted by transfusions but may also be transmitted by other means.

Adult↗
PubMed1996

Mice lacking p27(Kip1) display increased body size, multiple organ hyperplasia, retinal dysplasia, and pituitary tumors.

SUMMARY: Mice lacking p27(Kip1) have been created by gene targeting in embryonic stem cells. These mice are larger than the control animals, with thymus, pituitary, and adrenal glands and gonadal organs exhibiting striking enlargement. CDK2 activity is elevated about 10-fold in p27(-/-) thymocytes. Development of ovarian follicles seems to be impaired, resulting in female sterility. Similar to mice with the Rb mutation, the p27(-/-) mice often develop pituitary tumors spontaneously. The retinas of the mutant mice show a disturbed organization of the normal cellular layer pattern. These findings indicate that p27(Kip1) acts to regulate the growth of a variety of cells. Unexpectedly, the cell cycle arrest mediated by TGFbeta, rapamycin, or contact inhibition remained intact in p27(-/-) cells, suggesting that p27(Kip1) is not required in these pathways.

Animals↗
PubMed1996

Fibrosis in the peritoneum induced by scirrhous gastric cancer cells may act as "soil" for peritoneal dissemination.

BACKGROUND: Peritoneal metastases are one reason for the poor prognosis of scirrhous gastric cancer. However, the mechanism of peritoneal metastasis remains unclear. We therefore investigated the interaction between gastric cancer cells and peritoneal fibroblasts, in vivo and in vitro. METHODS: A human scirrhous gastric cancer cell line, OCUM-2MD3, and a human peritoneal fibroblast cell line, NF-2P, were established in our laboratory. We then investigated the effect of OCUM-2MD3 cells on the peritoneum of nude mice and on the proliferation of NF-2P cells, the effect of NF-2P cells on the migratory capability of OCUM-2MD3 cells, and the peritoneal fibrosis on the development of peritoneal metastasis. RESULTS: The proliferation of peritoneal fibroblasts was recognized in areas with and without cancer cell infiltration. Serum-free conditioned medium from the OCUM-2MD3 cells had induced peritoneal fibrosis in vivo and significantly stimulated the proliferation of NF-2P cells in vitro. The molecular weight (molecular weight ratio 25,000-43,000) of the growth factors produced by the OCUM-2MD3 cells was estimated by gel filtration high performance liquid chromatography. The migratory capability of the OCUM-2MD3 cells was significantly increased by the presence of NF-2P cells. Tumorigenicity in mice with peritoneal fibrosis was greater than in mice with normal peritoneum. CONCLUSIONS: Peritoneal fibrosis, formed by a factor secreted by scirrhous gastric cancer cells, may be congenial environment ("soil") for peritoneal metastases of scirrhous gastric carcinoma.

Adenocarcinoma, Scirrhous↗
PubMed1996

Effect of the selective CCKB receptor antagonist LY288513 on conditioned fear stress in rats.

In order to investigate the involvement of cholecystokinin (CCK) in the regulation of anxiety, the effect of the selective non-peptide CCKB receptor antagonist LY288513 ((4S, 5R)-N-(4-bromophenyl)-3-oxo-4,5-diphenyl-1-1-pyrazolidinecarboxamide+ ++) on freezing behavior induced by conditioned fear stress was examined using a time-sampling procedure. Rats were individually subjected to 5 min of inescapable electric footshock in a shock chamber. Twenty-four hours after the footshock, the rats were again placed in the shock chamber and observed for 5 min without shocks: this procedure is termed conditioned fear stress. Subcutaneous administration of LY288513 30 min before footshock (0.3 mg/kg) and 30 min before conditioned fear stress (0.03 mg/kg) reduced conditioned freezing. This indicates that LY288513 blocked both the acquisition and expression of conditioned fear. The relatively selective non-peptide CCKA receptor antagonist, lorglumide (D, L-4-(3,4-dichlorobenzoylamino)-5-(diphentylamino)-5-oxo-pent anoic acid), blocked the expression of conditioned fear, though only at a high dose (1.0 mg/kg). The peripheral non-peptide CCKA/B receptor antagonist, loxiglumide (D, L-4-(3,4-dichlorobenzoylamino)-5- (N-3-methoxypropyl-pentylamino)-5-oxo-pentanoic acid), failed to do so. These results suggest that brain CCKB receptors are involved in the regulation of anxiety.

Animals↗
PubMed1996

An RNA fragment consisting of the P7 and P9.0 stems and the 3'-terminal guanosine of the Tetrahymena group I intron.

On the basis of the nucleotide sequence of Tetrahymena group I intron, we constructed a 31 residue RNA that has the P7 stem and the 3'-terminal guanosine residue (3'-G) with a putative stem-loop structure (P9.0) intervening between them. For this model RNA (P7/P9.0/G), four residues around the guanosine binding site (GBS) in the P7 stem were found to exhibit much lower sensitivities to ribonuclease V1 than those of a variant RNA having adenosine in place of the 3'-G, suggesting that the 3'-G contacts around the GBS. NMR analyses of the imino proton resonances of the P7/P9.0/G RNA indicated that the base pairing in the GBS is retained on the interaction with the 3'-G, and that the two base pairs of the putative P9.0 stem-loop are definitely formed. Comparison of the RNA with its variants with either A (3'-A) or a deletion in place of the 3'-G suggested that the stability of the P9.0 stem-loop is affected by the GBS-3'-G interaction. The melting temperatures of the P9.0 stem-loop were determined from the UV absorbances of these RNAs, which quantitatively indicated that the P9.0 stem-loop is significantly stabilized by the interaction of the GBS with the 3'-G, rather than the 3'-A, and also by direct interaction with divalent cations (Mg2+, Ca2+ or Mn2+). Upon replacement of the G-C base pair by C-G in the GBS of the P7/P9.0/G RNA, the specificity was switched from 3'-G to 3'-A, as in the case of the intact intron.

Animals↗
PubMed1996

Regulation of cytokine production by sugi allergen-pullulan conjugate.

Sugi basic protein (SBP), a major allergen of Japanese cedar (Cryptomeria japonica) pollen, conjugated to pullulan (alpha-1,4'-, alpha-1,6'-glucan) reportedly suppresses IgE anti-SBP antibody production and enhances IgG anti-SBP antibody production in mice. We analyzed cytokine production by SBP-specific T cells after stimulation with an SBP-pullulan conjugate (SBP-P), native SBP, or a mixture of SBP and pullulan. When SBP-specific T cell lines were stimulated with the SBP-P conjugate in the presence of antigen-presenting cells (APC), the production of IFN-gamma, IL-4, IL-5, and IL-10 decreased compared with the cytokine levels produced by SBP-stimulated T cells. However, when these T cells were repeatedly stimulated with the SBP-P conjugate, the production of IFN-gamma increased progressively, while that of IL-4, IL-5, and IL-10 remained decreased compared with the T cells that were repeatedly stimulated with native SBP. Stimulation of the T cells with the mixture of SBP and pullulan showed little difference in the cytokine production profile from that observed after stimulation with native SBP alone. Interestingly, when the T cell lines stimulated repeatedly with SBP-P were subsequently stimulated with native SBP, a further increase in IFN-gamma production was observed, while IL-10 production decreased. Inhibition of IL-4 production was also observed when SBP-specific Th2 clones were stimulated with SBP-P. These results indicate that stimulation of T cells with SBP-P up-regulates Th1 cytokine production, while down-regulating that of Th2. It is, therefore, conceivable that immunotherapeutic treatment with the SBP-P conjugate rather than with conventional SBP solutions is preferable for improving Japanese cedar pollen allergy.

Allergens↗
PubMed1996

Studies on selectin blocker. 1. Structure-activity relationships of sialyl Lewis X analogs.

As part of our studies of selectin blockers, we prepared 1-deoxy-3'-O-sulfo LeX analogs (1-3), 1-deoxy-3'-O-phosphono LeX analogs (4), and 1-deoxy sLeX analogs (5-7), and examined their inhibitory activities against natural ligand (sLeX) binding to E-selectin, P-selectin, and L-selectin. The 1-deoxy sLeX 5 was up to 20 times more potent an inhibitor than the sLeX tetrasaccharide toward P- and L-selectin binding. This indicates that the modification of the 1 or 2 position of sLeX is useful in the design of a more potent selectin blocker.

E-Selectin↗
PubMed1996

Effect of KCA-098 on the function of osteoblast-like cells and the formation of TRAP-positive multinucleated cells in a mouse bone marrow cell population.

KCA-098 (3,9-bis(N,N-dimethylcarbamoyloxy)-5H-benzofuro[3,2-c]quinol ine-6-one), an analogue of coumestrol (a naturally occurring weak phytoestrogen), dose-dependently increased alkaline phosphatase activity of osteoblastic ROS 17/2.8 cells and freshly-isolated osteoblasts from neonatal mouse calvaria, and reduced cell proliferation. In addition, KCA-098 increased the synthesis of collagenese-digestible protein (CDP) of ROS 17/2.8 cells. On the other hand, KCA-098 had no effect on the basal synthesis of osteocalcin but reduced the 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)(2)D3)-induced increase in osteocalcin synthesized by ROS 17/2.8 cells. Therefore, KCA-098 had a bidirectional effect on the differentiation of osteoblasts (i.e., stimulating both alkaline phosphatase activity and synthesis of CDP and inhibiting osteocalcin synthesis). However, as KCA-098 stimulated the mineralization of chick embryonic bone in organ culture and recovered the bone density reduced by ovariectomy of rats, it would serve overall to stimulate the differentiation of osteoblasts. On the other hand, KCA-098 inhibited the formation of tartrate-resistant, acid phosphate-positive multinucleated cells (TRAP(+)MNC) induced by 1 alpha,25(OH)(2)D(3), parathyroid hormone (PTH), and prostaglandin E2 (PGE2) in cultures of mouse bone marrow cells, showing that it inhibits the formation of osteoclast-like cells. Coumestrol and 17beta-estradiol had no effect on the proliferation and alkaline phosphatase activity of ROS 17/2.8 cells. They did, however, dose-dependently inhibit osteoclast-like cell formation as well as KCA-098 did, indicating that the main action of coumestrol and 17beta-estradiol on bone tissue is the inhibition of bone resorption.

Acid Phosphatase↗
PubMed1996

Ataxia and epileptic seizures in mice lacking type 1 inositol 1,4,5-trisphosphate receptor.

The inositol 1,4,5-trisphosphate (InsP3) receptor acts as an InsP3-gated Ca2+ release channel in a variety of cell types. Type 1 InsP3 receptor (IP3R1) is the major neuronal member of the IP3R family in the central nervous system, predominantly enriched in cerebellar Purkinje cells but also concentrated in neurons in the hippocampal CA1 region, caudate-putamen, and cerebral cortex. Here we report that most IP3R1-deficient mice generated by gene targeting die in utero, and born animals have severe ataxia and tonic or tonic-clonic seizures and die by the weaning period. An electroencephalogram showed that they suffer from epilepsy, indicating that IP3R1 is essential for proper brain function. However, observation by light microscope of the haematoxylin-eosin staining of the brain and peripheral tissues of IP3R1-deficient mice showed no abnormality, and the unique electrophysiological properties of the cerebellar Purkinje cells of IP3R1-deficient mice were not severely impaired.

Animals↗
PubMed1996

A comparison of the structure of radiation oncology in the United States and Japan.

PURPOSE: The United States and Japan have very different backgrounds in their medical care systems. In the field of radiation oncology, national surveys on structure have been conducted for both countries and compared to illustrate any similarities and differences present from 1989-1990. METHODS AND MATERIALS: The Patterns of Care Study Facility Survey conducted in 1989 in the United States and the National Survey of Structure in Japan in 1990 were compared to evaluate the equipment pattern, staffing pattern, compliance rate with the "blue book" (3) guideline, and the geographic distribution of institutions. RESULTS: In the United States, a total of 598,184 (49% of the total of newly diagnosed) patients were treated with radiation therapy. In Japan, 62,829 (approximately 15% of the total of newly diagnosed) patients were treated. The numbers of external megavoltage treatment machines were 2,397 in the United States and 494 in Japan. The numbers of full time equivalent (FTE) radiation oncologists were 2,335 in the United States and 366 in Japan. Only 15% of United States facilities and 11% of Japan facilities complied with the narrow blue book guideline for the patients per FTE radiation oncologist (200-250), while the most common ratio was 151-200 patients/FTE in the United States and 51-100 in Japan. In Japan, more than 60% of institutions were staffed by a part-time radiation oncologist (FTE < 1.0). Between geographic regions, there was variation in the percentage of cancer patients treated with radiation therapy for both the United States (42-56%) and Japan (6-25%). CONCLUSION: There is a major difference in the usage of radiation therapy for treating cancer between the United States and Japan with 49% of all new cancer patients treated in the United States and approximately 15% treated in Japan. Equipment structure in the United States is more complete than in Japan with important differences in treatment simulators, treatment planning computers, and support personnel. High dose rate intracavitary radiation is commonly available in Japan and there are geographic differences in radiation oncology utilization in both countries.

Cancer Care Facilities↗
PubMed1996

Hepatitis C biochemical remission and viral replication in haemodialysis patients.

The natural course of non-A, non-B (type C) hepatitis was studied in 62 haemodialysis patients. From the onset of the disease, serum alanine aminotransferase levels were monitored monthly for 9-218 mon (median 115). After fluctuation of aminotransferase levels for 1-206 mon (median 39), 57 (92%) patients showed normalization of these levels lasting until the end of the follow-up, which was for > 2 yr in 31 (50%) cases and for > 5 yr in 15 (24%) cases. At the end of follow-up, hepatitis C viraemia was assessed by reverse transcription-polymerase chain reaction (RT-PCR) and branched DNA (bDNA) assay. Viraemic levels were significantly lower in the 15 patients with normal aminotransferase for > 5 yr (median RT-PCR + ve/bDNA-ve, range RT-PCR-ve to 10(6.7) Eq/mL) than in the 47 cases with normal levels for < 5 yr (median 10(6.6), range RT-PCR + ve/bDNA-ve to 10(7.6) Eq/mL) (P < 0.01). Moreover, a significant inverse relation was observed between viraemic levels and the duration of aminotransferase normalization (r = -0.46, P < 0.01). These findings indicate that biochemical remission of hepatitis C may be frequent in haemodialysis patients and may be related to viral attenuation.

Adult↗
PubMed1996

Infection with GB virus C in leprous patients in Japan.

The detection of hepatitis C virus (HCV) in blood donors and patients with acute and chronic hepatitis has brought to the fore another virus or viruses which can be transmitted parenterally and induce liver disease. The RNA of a candidate virus designated GB virus C (GBV-C) was determined by the polymerase chain reaction with primers deduced from a helicase-like region in 229 leprous patients in Japan. GBV-C RNA was detected in 12 (5.2%) patients, and HCV RNA in 41 (18%). Three patients were coinfected with GBV-C and HCV. The nine patients infected with GBV-C alone had aminotransferase levels lower than the three patients with the mixed infection or the 38 patients infected with HCV only (P < 0.001). Sequence comparison within 100 base pairs in the helicase-like region suggested that two, three and three patients, respectively, would have been infected with three distinct strains of GBV-C. These results indicate that patients with leprosy are at increased risk for infection not only with HCV, but also with GBV-C, and that the infection with GBV-C alone would not induce hepatic injuries as severe as HCV infection.

Adult↗
PubMed1996

Treatment of high-risk acute lymphoblastic leukemia in children using the AL851 and ALHR88 protocols: a report from the Kyushu-Yamaguchi Children's Cancer Study Group in Japan.

A total of 125 children, who were diagnosed as having high-risk acute lymphoblastic leukemia (ALL), were treated with two consecutive protocols designated as AL851 (1985-1988) and ALHR88 (1988-1990). All patients received induction therapy consisting of vincristine (VCR), prednisolone (PSL), daunorubicin (DNR), and I-asparaginase (I-Asp). In the ALHR88 protocol, the patients whose blasts in the bone marrow (BM) were > or = 25% on day 14 of induction therapy and who were classified into T-cell type received additional cytosine arabinoside (AraC). After consolidation with intermediate-dose methotrexate (MTX), reinduction therapy including VCR, dexamethasone, and adriamycin followed by high-dose AraC was done for all patients. Intrathecal MTX and 24Gy of cranial irradiation were used to prevent central nervous system leukemia. A maintenance therapy consisting of 6-mercaptopurine, cyclophosphamide, MTX, DNR, VCR, and AraC was administered for 3 years after achieving a complete remission (CR). CR was achieved in 51/55 (92.7%) for AL851 and 68/70 (97.1%) for ALHR88. The 5-year event-free survival rates were 49.1 +/- 6.7% in AL851 and 62.5 +/- 6.1% in ALHR88. The factors related to a poor prognosis were a high initial leukocyte count of greater than 50 x 10(9)/L (P < 0.001), an L2 morphology of leukemic cells by FAB classification (P = 0.009), the chromosomal abnormality (P = 0.004) and high residual leukemic cells in BM (> or = 25%) on day 14 of induction therapy (P < 0.001). Taking these factors into consideration, more intensive protocols were started in 1990 for the patients with high-risk ALL.

Adolescent↗
PubMed1996

Electron microscopic evidence of impaired intramembrane particles and instability of the cytoskeletal network in band 4.2 deficiency in human red cells.

To obtain direct evidence of impaired intramembrane particles (IMPs) and a deranged cytoskeletal network in situ in human red cells of band 4.2 deficiency, electron microscopic studies were performed utilizing the freeze fracture method for IMPs and the quick-freeze deep-etching method for the cytoskeletal network. Three patients with three different previously identified mutations of the band 4.2 gene, i.e., band 4.2 Komatsu (homozygous; codon 175 GAT --> TAT), band 4.2 Nippon (homozygous; codon 142 GCT --> ACT), and band 4.2 Shiga (compound heterozygous; codon 317 CGC --> TGC and codon 142 GCT --> ACT), were selected for this study. The decrease in the number of IMPs with increase in their size was most marked in band 4.2 Komatsu, which was clinically most severe with no band 4.2 protein. In this regard, in band 4.2 Nippon, which showed moderate severity in clinical hematology with a nearly missing band 4.2 protein, increased sizing was less marked. The abnormalities in IMPs were the least in band 4.2 Shiga, which demonstrated compensated hemolysis with band 4.2 protein in a trace amount. The extent of the impairment of IMPs may be reflected by the total absence or the presence of band 4.2 protein even in a trace amount and/or by the specific site(s) of the mutation of the band 4.2 gene. Derangement of the cytoskeletal network was also observed in these three patients. It was most abnormal in band 4.2 Komatsu, and less so in band 4.2 Nippon and in band 4.2 Shiga. These results clearly indicate that 1) band 4.2 plays an important role not only in its binding to band 3 but also to the skeletal network (mostly to spectrins) vertically, and 2) its deficiency produces critical abnormality in maintenance of the structural and functional integrity of the integral proteins (such as band 3), as well as the cytoskeletal network.

Amino Acid Sequence↗
PubMed1996

Case of myoepithelioma originating from the palate: collagenogenesis in myoepithelial tumor cells.

We report a case of myoepithelioma of the palate in a 53-yr-old man. Myoepithelioma cells consisting of both plasmacytoid type and spindle type were obtained. A reticular pattern composed of a mosaic arrangement of hyaline-like abundant cytoplasm, and scant matrix and considerable fiber formation were characteristic features of the plasmacytoid type; granular cytoplasm and a snake-like shape were characteristic features of the spindle type. These are important points in differentiating this tumor from cellular type pleomorphic adenoma. The present study shows that tumorous myoepithelial cells can synthesize and secrete extracellular components such as proteoglycans, basal lamina, collagen fibers, and elastic fibers.

Adenoma, Pleomorphic↗