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Biomedical subjects

M Miyata

Publications and source records attributed to M Miyata.

At least 271 records · Page 15Linked to original sources

The antitumor effect of hyperthermia combined with fluorouracil and its analogues.

The effectiveness of 5-fluorouracil (5-FU), FT-207 and FT-207 + uracil in combination with two repetitions of 43 degrees C hyperthermia in the treatment of the Meth-A-Fibrosarcoma and Sarcoma-180 was examined in vivo in BALB/c mice. The antitumor effect was evaluated in terms of inhibition of tumor growth by measuring the tumor for 7 days. The 5-FU concentration in each tumor was also monitored. Hyperthermia combined with FT-207 or FT-207 + uracil showed a synergistic effect for the inhibition of growth of both tumors which was not observed with 5-FU. There were no significant differences in the intratumoral concentration of 5-FU in unheated or heated Sarcoma-180 for any drug treatment after the first hyperthermia treatment, except for significant decreases in the group given 5-FU with the first hyperthermia treatment. After the second hyperthermia treatment, significant decreases in the concentration of 5-FU and FT-207 + uracil were observed. In the Meth-A-Fibrosarcoma, the intratumoral concentration of 5-FU decreased significantly in the group given 5-FU and increased significantly in the group given FT-207 + uracil after the first hyperthermia treatment, while there were significant decreases in 5-FU, FT-207 and FT-207 + uracil administered with the second hyperthermia treatment. Hyperthermia combined with FT-207 or FT-207 + uracil is considered to be effective.

Animals↗

Migration of donor cells into the thymus is not essential for induction and maintenance of systemic tolerance after liver transplantation in the rat.

In this study, we show that cells encoded by donor-type major histocompatibility complex (MHC) class I antigens effectively migrate into the thymus of the host after liver transplantation. However, the thymus is not essential for the induction and maintenance of tolerance after orthotopic rat liver transplantation (OLT). Liver allografted rats in the DA(RT1a) into PVG (RT1c) combination survived without immunosuppressive agents. The thymus of the host showed a transitory atrophy and returned to normal weight 4 weeks after OLT. Donor antigens were detected in the host thymus after OLT. Adult PVG rats that had been thymectomized 1 week before implantation of DA liver grafts showed liver graft survival without immunosuppression. DA heart grafts were heterotopically transplanted into the PVG thymectomized, liver-grafted rats 1-4 weeks after OLT. No rejection of the cardiac allografts was observed. Systemic tolerance was induced and maintained in the absence of the thymus.

Animals↗

TGF-beta upregulates interleukin 6 production by rat glomerular epithelial cells in vitro.

BACKGROUND: Glomerular epithelial cells (GECs) play an important role in maintaining normal glomerular permselectivity in vivo. Recent in-vitro studies have suggested that GECs are able to secrete substances which may modulate glomerular injury. Interleukin 6 (IL-6) has been shown to be a potent mediator of glomerular injury. It is also known that IL-6 could be produced by various cells. METHODS: IL-6 production by rat GECs in culture was examined in this study. IL-6 bioactivity in conditioned medium collected from cultured GECs (GEC-CM) was measured using IL-6 dependent murine hybridoma cell line, namely B9 cells. IL-6 gene expression by GECs was analysed by reverse transcriptase polymerase chain reaction (RT-PCR). Effects of recombinant IL-6 on the proliferation of GECs and type IV collagen secretion by GECs were evaluated to examine the possible role of GECs derived IL-6. RESULTS: GEC-CM stimulated B9 cells growth in a dose dependent fashion. The mitogenic activity was inhibitable by anti-murine IL-6 antibody. De-novo synthesis of IL-6 was suggested by the demonstration of IL-6 mRNA by GECs using the RT-PCR. Secretion of IL-6 by GECs was increased by transforming growth factor beta but not by IL-1 beta. Recombinant murine IL-6 stimulated GECs growth and their type IV collagen secretion. CONCLUSIONS: These results indicate that rat GECs could produce IL-6 which may modulate glomerular inflammation and that IL-6 may function as an autocrine factor for GECs.

Animals↗

Concomitant use of prostaglandin E1 and prednisolone; inhibition of superoxide anion production by polymorphonuclear leucocytes.

We investigated the effect of prostaglandin E1 (PGE1) or prednisolone on superoxide anion production by polymorphonuclear leucocytes (PMN) stimulated by opsonized zymosan (OZ). The production of superoxide anion by PMN was significantly suppressed by treatment with either PGE1 or prednisolone. Concomitant use of PGE1 and prednisolone suppressed it significantly more than PGE1 or prednisolone alone. Both PGE1 and prednisolone suppressed the Ca2+ influx into PMN, which was a crucial event for production of superoxide anion in stimulation by OZ. The effect of concomitant use of PGE1 and prednisolone in vivo was confirmed in rat peritonitis. The additional use of PGE1 with prednisolone may provide a strategy to reduce the amount of prednisolone required in treatments.

Alprostadil↗

[Catamenial pneumothorax with diaphragmatic and visceral plural endometriosis].

A 47-year-old woman was admitted to our hospital because of two episodes of right pneumothorax. After continuous suction through a thoracic drain, a computerized tomographic scan showed that air was still trapped between lung lobes. Video-assisted thoracic surgery revealed a bulla on the visceral pleural of the upper lobe (S2) and several dark-red spots and white-coated lesions surrounding a defect of the diaphragm. The involved portions of the diaphragm and of the lung were excised. Microscopic examination of the excised specimens showed endometriosis. Catamenial pneumothorax may be caused by intrathoracic endometriosis, but very few cases in which pulmonary or visceral pleural endometriosis was demonstrated histologically have been reported.

Blister↗

Analysis of human 65 kD heat shock protein mRNA using polymerase chain reaction in synovia of rheumatoid arthritis patients.

To examine the role of 65kD heat shock protein (HSP) on the etiology of RA, we investigated the expression of 65kD HSP mRNA in the synovia of patients with rheumatoid arthritis (RA). Synovial membranes from 10 patients with RA and 2 patients with non-inflammatory arthritis were examined for the expression of the 65kD HSP mRNA by the reverse transcription-polymerase chain reaction (RT-PCR) method. The mRNA of 65kD HSP was detected in all 10 samples from the RA patients and in the 2 samples from the patients with non-RA using semi-quantitative PCR and the difference in its expression level between the two groups was found not to be significant. By sequence analysis of the 412 bp PCR products, the 65kD HSP protein was confirmed to be human-origin. These data suggest that the 65kD HSP expressed in rheumatoid synovia is human origin and the lymphocytic reaction to the HSP may play an important role in the pathogenesis of RA.

Adult↗

Synthesis and properties of oligo-omega-amino acids derivatives containing nucleosides.

Nucleic acid analogs, that consist of oligo-omega-amino acids as main chains were synthesized. At first, hydroxyl group of deoxy and ribonucleic acid was converted into amino or carboxylic acid group. Then, amino acid derivatives containing aminonucleoside or nucleoside-5'-carboxylic acid at alpha-position were synthesized. Amino acids used in this paper were L-glutamic acid, L-2-amino adipic acid (L-homo glutamic acid), L-ornithine, and L-lysine. These amino acid derivatives containing nucleoside were oligomerized by activated ester methods and Merrifield's solid phase synthesis. The properties of these analogs were studied and compared with oligo-alpha-amino acid derivatives containing nucleoside at omega-position.

Amino Acids↗

Structure of a gene and cDNA of a major constitutive form of testosterone 6 beta-hydroxylase (P450/6 beta A) encoding CYP3A2: comparison of the cDNA with P450PCN2.

P450/6 beta A gene was isolated from a rat genomic library and its encoding protein was characterized by the expression of the corresponding cDNA in COS-1 cells. Between exon regions of P450/6 beta A gene and P450PCN2 cDNA (F. J. Gonzalez, B.-J. Song, and J. P. Hardwick (1986) Mol. Cell. Biol. 6, 2969-2976), 12 nucleotide differences were observed, involving two amino acid changes, His-->Asp [429] and Asp-->Gly [445], respectively. A cDNA (6 beta-A cDNA), whose nucleotide sequence was completely identical with the corresponding exon of P450/6 beta A gene, was isolated from a rat cDNA library. Northern blotting using specific oligonucleotide probes showed that 6 beta-A mRNA, but not P450PCN2 mRNA, was a major form in livers of the male rats. 6 beta-A protein expressed in COS-1 cells (at about 0.1 to 0.3% of total microsomal protein) catalyzed testosterone 6 beta-hydroxylation. The reaction was enhanced by the addition of NADPH-P450 reductase (2.5-fold) and by the simultaneous addition of cytochrome b5 and NADPH-P450 reductase (13.7-fold). Catalytic properties of 6 beta-A for typical CYP3A substrates were consistent with those of purified rat P450(6 beta-1) and P450(6 beta-3), corresponding, respectively, to CYP3A2 or the variant form (K. Nagata, F. J. Gonzalez, Y. Yamazoe, and R. Kato (1990) J. Biochem. 107, 718-725). Apparent Michaelis constants (Km) of 6 beta-A for testosterone 6 beta-hydroxylation and a O-dealkylation ratio of propoxycoumarin to pentoxycoumarin, however, showed higher degrees of similarity to those of purified P450(6 beta-3) than those of P450(6 beta-1).

Amino Acid Sequence↗

[Diagnostic imagings and embolotherapy for the superior mesenteric vein-inferior vena cava shunt].

Diagnostic imaging and embolization therapy for the uncommon portal and mesenteric vein-inferior vena cava shunt (PV.SMV-IVC shunt) are reported. As the frequency of clinical symptoms such as hematemesis, melena and confusion caused by gastrointestinal varices, or hepatoencephalopathy was about 40%, it was important for this disease entity to be diagnosed with noninvasive diagnostic images. The careful examination of the area around the right renal vein was able to overcome the low diagnostic rate of 20-40% obtained with US and CT images. In cases of simple PV.SMV-IVC shunt without gastrointestinal varices, embolization therapy using steel coils and done by the intravenous approach is easy and noninvasive. On the other hand, in cases of complex PV-SMV-IVC shunt with gastrointestinal varices, dual balloon occluded embolization therapy using a liquid sclerosing agent and done by the intravenous and portal approaches is preferable.

Adult↗

Beneficial effects of cyclosporine on reoxygenation injury in hypoxic rat liver.

The effect of CsA on hypoxia-reoxygenation injury was studied in perfused rat livers. CsA did not attenuate hypoxic injury, as assessed by the release of lactate dehydrogenase and mitochondrial aspartate aminotransferase. During reoxygenation, the release of lactate dehydrogenase was also not affected by CsA. However, the release of mitochondrial aspartate aminotransferase into the cytosol, which indicates mitochondrial injury, was significantly reduced by CsA. The effect of CsA on mitochondrial function during hypoxia-reoxygenation was also investigated. CsA administration increased both the respiratory control ratio and the adenine nucleotide content after reoxygenation in both isolated mitochondria and perfused livers. In addition, glucose production by perfused livers after reoxygenation was increased by CsA. We conclude that the beneficial effect of CsA on hypoxia-reoxygenation injury may be partly due to protection of the mitochondria against reoxygenation injury.

Animals↗

A technique for complete thymectomy in adult rats.

50 open thymectomies were performed in adult rodents using intubation combined with a fibrin glue able to prevent hemorrhage and pulmonary air leakage. This method had a 100% success rate and lower mortality than the ordinal suction procedure. Although the conventional suction thymectomy has been widely used, the open thymectomy method would permit more complete thymectomies for immunological studies.

Animals↗

The rejection mechanism of rat pancreaticoduodenal allografts with a class I MHC disparity.

The present study has demonstrated for the first time that PVG.R1 (RT1.AaBcDcCc) pancreatic grafts are rejected by so-called "low"-responder PVG (RT1.AcBcDcCc) recipients with an isolated class I MHC disparity (mean survival time; MST: 21.4 +/- 1.8 days, n = 5), whereas PVG.R1 heart grafts are able to survive indefinitely (MST: > 100 days, n = 5). Splenic CD4+ T cells but not CD8+ T cells from the PVG recipients of PVG.R1 pancreatic grafts show a remarkable proliferative response against donor class I RT1.Aa alloantigens, while only a minimal proliferation is observed in the PVG recipients of PVG.R1 heart grafts or naive PVG rats. Naive PVG rats display an extremely low frequency of IL-2-producing helper T cell precursors (fThp) of 1/40,609 +/- 15,441 against class I RT1.Aa alloantigen. The PVG recipients of PVG.R1 heart grafts have a slightly greater fThp of 1/17,326 +/- 6822. On the other hand, the PVG recipients that rejected PVG.R1 pancreatic grafts show a significantly increased fThp of 1/5030 +/- 3396 compared with those of PVG.R1 heart grafts (P < 0.05) or naive PVG rats (P < 0.01). The frequency of cytotoxic T cell precursors (fTcp) increases slightly in the PVG recipients of PVG.R1 pancreatic grafts (1/1848 +/- 330) compared with those of PVG.R1 heart grafts (1/2215 +/- 2131) or naive PVG rats (1/2476 +/- 585). The size of cytotoxic T cell clones alone does not adequately account for a proliferation sufficient to complete the rejection of pancreatic grafts. The PVG recipients of PVG.R1 pancreatic grafts, but not heart grafts, demonstrate a strong cytotoxic alloantibody response to donor class I RT1.Aa alloantigens. In the study of alloantibodies, IgM is detected mainly in the early phase and IgG in the late phase during the course of pancreatic rejection. It is determined that in blocking studies by FACS analysis these antibodies target class I MHC antigens. These results suggest that cytotoxic T cells do not appear to be responsible for the rejection of PVG.R1 pancreatic grafts in PVG recipients. Rather, the rejection is mediated by CD4+ T cells and complement-fixing antibodies directed at class I MHC antigens.

Animals↗