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Biomedical subjects

M Miyata

Publications and source records attributed to M Miyata.

At least 55 records · Page 3Linked to original sources
PubMed2001

[A case of advanced non-small-cell lung cancer responding remarkably to weekly chemotherapy with paclitaxel].

We report a case of advanced non-small-cell lung cancer showing remarkable response to weekly administration of paclitaxel. The patient was a 63-year-old man who had IIIB advanced lung adenocarcinoma. Though he received one course of cisplatin and etoposide, the tumor was not reduced. In addition, because of his nauseous response, he no longer wanted to receive that chemotherapy. The chemotherapy regimen was therefore changed to weekly administration of vinorelbine, but this was not effective. Next, after changing the regimen to the weekly administration of paclitaxel, the tumor was remarkably reduced following 3 courses. This case shows that weekly administration of paclitaxel may be an effective chemotherapy for non-small cell lung cancer not responsive to first-line chemotherapy.

Adenocarcinoma↗
PubMed2000

Targeted disruption of soluble epoxide hydrolase reveals a role in blood pressure regulation.

Renal microsomal cytochrome P-450 monooxygenase-dependent metabolism of arachidonic acid generates a series of regioisomeric epoxyeicosatrienoic acids that can be further metabolized by soluble epoxide hydrolase to the corresponding dihydroxyeicosatrienoic acids. Evidence exists that these metabolites affect renal function and, in particular, blood pressure regulation. To examine this possibility, blood pressure and renal arachidonic acid metabolism were examined in mice with a targeted disruption of the soluble epoxide hydrolase gene. Systolic blood pressure of male soluble epoxide hydrolase-null mice was lower compared with wild-type mice in both the absence and presence of dietary salt loading. Both female soluble epoxide hydrolase-null and wild-type female mice also had significantly lower systolic blood pressure than male wild-type mice. Renal formation of epoxyeicosatrienoic and dihydroxyeicosatrienoic acids was markedly lower for soluble epoxide hydrolase-null versus wild-type mice of both sexes. Although disruption of soluble epoxide hydrolase in female mice had minimal effects on blood pressure, deletion of this gene feminized male mice by lowering systolic blood pressure and altering arachidonic acid metabolism. These data provide the first direct evidence for a role for soluble epoxide hydrolase in blood pressure regulation and identify this enzyme as a novel and attractive target for therapeutic intervention in hypertension.

Animals↗
PubMed2000

Combined therapy with conservative surgery, radiotherapy, and regional chemotherapy for maxillary sinus carcinoma.

BACKGROUND: Current goals for the treatment of carcinoma of the maxillary sinus include the preservation of vision, ability to eat, ability to communicate, and appearance as well as cure. METHODS: Seventy-five Japanese patients who presented with maxillary sinus carcinoma between 1979 and 1997 were analyzed retrospectively. There were 48 males and 27 females with a median age of 62 years. The mean follow-up period was 73 months. All patients underwent multimodality therapy including surgery through a sublabial incision, radiotherapy, and regional chemotherapy. The regional lymph nodes were treated only in those patients with cervical lymph node involvement. RESULTS: The 5-year and 10-year overall survival rates were 76% and 66%, respectively. In 65 patients with squamous cell carcinoma, the 5-year and 10-year overall survival rates were 77% and 66%, respectively. All 23 patients with orbital involvement retained the orbital contents and 17 patients demonstrated adequate ocular function. There was no disease recurrence reported among patients with involvement of the foramen rotundum or the foramen ovale, whereas two of the three patients with invasion of the foramen lacerum developed disease recurrence. There were 12 complications in 12 patients, including double vision (4 patients), cataracts (3 patients), trismus (4 patients), and fistula formation (1 patient). CONCLUSIONS: Control of the primary tumor site is important in the curative treatment of patients with maxillary sinus carcinoma. Combined therapy with conservative surgery, radiotherapy, and regional chemotherapy appears to be an effective method for local control and the preservation of ocular function.

Antimetabolites, Antineoplastic↗
PubMed2000

Remarkable wavelength-dependent photoreactions of the bis(diazo) ketone having inequivalent diazo groups: studies in fluid solutions and in low-temperature matrixes

The photoreactions of the bis(diazo) ketone 11, which has two inequivalent diazo groups, have been investigated in solutions at room temperature and in matrixes at 12 K. Irradiation of 11 in benzene containing methanol gave a mixture of the spironorcaradiene 13 and the diazo ketone 17 as primary isolable photoproducts. The former 13 originated from the diazo ketene 20, which was formed from the initial extrusion of N(2) from the 2-position of 11, while the latter product 17 was derived from the diazo ketene 24 which was generated by the initial decomposition of the diazo group at the 4-position of 11. The product distribution was remarkably dependent upon the excitation wavelength: 13 was predominantly obtained in the photolysis with light of >350 nm, while the irradiation with long-wavelength light (>420 nm) exclusively gave 17. The consistent wavelength effects were observed in photoreactions in an Ar matrix at 12 K. The irradiation of 11 matrix-isolated in Ar with light of >350 nm afforded 20 in preference to the isomer 24 as the first-formed intermediates, while 24 was mainly obtained in the long-wavelength irradiation (>420 nm). On the basis of these experimental data, we conclude that the short-wavelength irradiation of 11 causes a preferential cleavage of the diazo group at the 2-position and that the selective extrusion of N(2) from the 4-position is practically achieved by the irradiation with long-wavelength light. The reason for the selective cleavage of the two inequivalent diazo groups of 11 is discussed on the basis of theoretical calculations with the PM3 CI method.

Journal Article↗
PubMed2000

Targeted disruption of the nuclear receptor FXR/BAR impairs bile acid and lipid homeostasis.

Mice lacking the nuclear bile acid receptor FXR/BAR developed normally and were outwardly identical to wild-type littermates. FXR/BAR null mice were distinguished from wild-type mice by elevated serum bile acid, cholesterol, and triglycerides, increased hepatic cholesterol and triglycerides, and a proatherogenic serum lipoprotein profile. FXR/BAR null mice also had reduced bile acid pools and reduced fecal bile acid excretion due to decreased expression of the major hepatic canalicular bile acid transport protein. Bile acid repression and induction of cholesterol 7alpha-hydroxylase and the ileal bile acid binding protein, respectively, did not occur in FXR/BAR null mice, establishing the regulatory role of FXR/BAR for the expression of these genes in vivo. These data demonstrate that FXR/BAR is critical for bile acid and lipid homeostasis by virtue of its role as an intracellular bile acid sensor.

Animals↗
PubMed2000

Anti-tumor immunity against CT26 colon tumor in mice immunized with plasmid DNA encoding beta-galactosidase fused to an envelope protein of endogenous retrovirus.

Endogenous retroviral gene products have been recognized as being expressed in human cancerous tissues. However, these products have not been shown to be antigenic targets for T-cells, possibly due to immune tolerance. Since carcinogen-induced colon tumor CT26 expresses an envelope protein, gp70, of an endogenous ecotropic murine leukemia virus that is comparable to human tumor-associated antigens, we examined whether a DNA vaccine containing the gp70 gene induces protective immunity against CT26 cells. Injection of mice with plasmid DNA (pDNA) encoding gp70 alone failed to induce anti-gp70 antibody (Ab) or anti-CT26 cytotoxic T lymphocyte (CTL) responses. However, immunization with pDNA encoding the beta-galactosidase (beta-gal)/gp70 fusion protein induced anti-gp70 Ab and anti-CT26 CTL responses and conferred protective immunity against CT26 cells. These results indicate that beta-gal acts as an immunogenic carrier protein that helps in the induction of immune responses against the poorly immunogenic gp70. Considering these results, it is possible that potential tolerance to the endogenous retroviral gene products expressed by human tumors may be overcome by DNA vaccines that contain an endogenous retroviral gene fused to genes encoding immunogenic carrier proteins.

Animals↗
PubMed2000

Identification of cAMP analogue inducible genes in RAW264 macrophages.

RNA was isolated from RAW264 cells treated with or without 8-Br-cAMP and the differential display and subtractive hybridization methods were performed. One hundred and twenty-five differentially displayed bands were identified. Upon Northern blot analysis, only three of these bands were confirmed as cAMP inducible mRNAs, named cI-1, cI-2, and cI-3 (for cAMP inducible genes 1-3). The cI-3 probe was identical to a previously known gene, gly96. Using the novel cI-1 and cI-2 partial cDNAs as probes, a mouse macrophage cDNA library was screened and the two full length genes were cloned, sequenced, and characterized as encoding large hydrophobic proteins. One hundred and fifteen partial cDNA clones from a subtractive hybridization library were also screened by Northern blot and 64 were found to be cAMP inducible. Of these, 45 represented 31 known unique genes in the GenBank nr database (cI-4-34), and 19 clones representing 15 unique sequences were not in the nr database (cI-35-49). One of the previously known genes was ABC1, the Tangier disease gene, which was identified from four independent partial cDNAs. ABC1 was upregulated in RAW cells by cAMP, concurrent with the cAMP induction of lipid efflux to apolipoprotein A1.

Animals↗
PubMed2000

Classical conditioning of oxidative DNA damage in rats.

This study investigated whether the formation of 8-hydroxydeoxyguanosine (8-OH-dG), a known oxidative DNA modification relevant to carcinogenicity, can be classically conditioned to a novel taste in order to clarify the possible role of the central nervous system (CNS) or psychological stress on cancer initiation via a classical conditioning mechanism. Male Wistar rats underwent one or two conditioned taste aversion (CTA) experiments in which ferric nitrilotriacetate (Fe-NTA), which has renal toxicity and can induce renal cell carcinoma, served as a visceral unconditioned stimulus (US), and a saccharin solution (SAC) was used as a conditioned stimulus (CS). The 8-OH-dG levels in the group conditioned with the combination of SAC and Fe-NTA significantly increased as compared to those of the uncombined groups by two repeats of the conditioning procedure (P=0.013). The rats that showed a painful response at the Fe-NTA administration had significantly higher values of 8-OH-dG than those without pain (P=0. 003). These results not only provide the first evidence regarding classical conditioning of oxidative DNA damage using the CTA procedure, but also suggest the involvement of the CNS and psychological stress in the pathogenesis of cancer via oxidative DNA damage.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2000

Intercalation of alkylamines into an organic polymer crystal

Organic solid-state synthesis allows formation of products that are difficult or impossible to produce by conventional methods. This feature, and the high degree of reaction selectivity that can be achieved, is a direct result of the control over the relative orientation of the reactants afforded by the solid state. But as the successful development of 'topochemical reactions' requires the careful design of suitable reactant crystals, the range of both reactions and products amenable to this approach has been limited. However, recent advances in organic crystal engineering, particularly the rational design of complex solid architectures through supramolecular preorganization, have renewed interest in topochemical reactions. Previously, we have orientated muconate monomers--diene moieties with a carboxylate group on each end--using long-chain n-alkylammonium ions, such that the topochemical photopolymerization of the solid-state reactants produces layered crystals of stereoregular and high-molecular-mass polymers. Here we show that these polymer crystals are capable of repeated, reversible intercalation by conversion to the analogous poly(carboxylic acid), followed by transformation into a number of poly(alkylammonium muconate)s upon addition of the appropriate amine. Introduction of functional groups into these crystals may allow the design of organic solids for applications such as molecular recognition, separation and catalysis, thereby extending the range and practical utility of current intercalation compounds.

Journal Article↗
PubMed2000

Lympholeukemia in madai Pagrus major in Japan.

Lympholeukemia has been occurring to an epizootic extent with mass mortality in 1 and 2 yr old madai (= Japanese red sea bream) Pagrus major in the winter season (October-May) in the western regions of Japan since 1975. Diseased fish displayed severe anemia and markedly increased numbers of neoplastic lymphocytoid and lymphoblastoid cells in the blood. Neoplastic cells originated in the splenic lymphatic cells and systemically caused severe metastatic lesions in the heart, liver, kidney, digestive tracts, gills and the lateral musculature. Electron microscopy revealed adeno-like viral particles (78 to 83 nm in diameter) in the nucleus of lymphoblastoid cells which appeared in the early prevalent stage but no viral particles in the lymphocytoid cells or plasmacytoid cells, which subsequently increased in number. In this paper, we describe light and electron microscopic features of neoplasms and neoplastic cells.

Animals↗
PubMed2000

Injection of plasmid DNA into the gastric mucosa induces mucosal and systemic immunity.

Nearly all mucosal surfaces participate in a common mucosal immune system, and application of an antigen to one mucosal surface elicits local as well as distant mucosal immune responses. However, whether the gastric mucosa is a part of this network has not been examined directly. We show here that the injection of plasmid DNA encoding beta-galactosidase into the gastric wall caused transfection of gastric mucosal epithelial cells, induced systemic and mucosal antibody responses at both local (digestive tract) and distant (genital and respiratory tracts) sites, and induced cytotoxic T lymphocyte responses in the spleen and the mesenteric and iliac lymph nodes.

Animals↗
PubMed2000

Unmethylated oligo-DNA containing CpG motifs aggravates collagen-induced arthritis in mice.

OBJECTIVE: To investigate the effects of an intradermal injection of an unmethylated oligodeoxynucleotide (ODN) containing CpG motifs on the severity of collagen-induced arthritis (CIA). METHODS: CIA was induced in DBA/1 LacJ mice by immunization with bovine type II collagen (CII) in Freund's complete adjuvant followed 3 weeks later by immunization with CII in Freund's incomplete adjuvant (yielding CIA mice). Unmethylated ODN containing a CpG motif was injected intradermally into DBA/1 LacJ mice at a dosage of 20 microg (yielding CpG-CIA mice) 1 week prior to the first immunization with CII. Unmethylated ODN containing a GpC motif instead of a CpG motif and ODN containing a methylated CpG motif were used to produce controls (GpC-CIA mice and mCpG-CIA mice, respectively). After the second immunization with CII, arthritis scores were measured weekly up to the eighth week. At the eighth week, the mice were killed, histopathologic changes in the ankle joints were examined, and titers of interferon-gamma (IFNgamma) in the supernatants of splenocytes (1 x 10(7)) stimulated in culture by CII for 3 days were determined by enzyme-linked immunosorbent assay. RESULTS: CpG-CIA mice had significantly higher arthritis scores than CIA mice. CpG-CIA mice had more severe histopathologic changes than CIA mice and mCpG-CIA mice. Moreover, splenocytes in CpG-CIA mice produced higher IFNgamma titers in response to CII than did splenocytes in CIA mice and mCpG-CIA mice. CONCLUSION: Injection of unmethylated oligo-DNA containing CpG motifs aggravated CIA through activation of the Th1-type immune response, suggesting that microbial infection could be one of the mechanisms for aggravation or exacerbation of arthritis or, alternatively, that such infection could be an adjuvant in the induction of arthritis in rheumatoid arthritis.

Animals↗
PubMed2000

Circadian rhythm of serotonin N -acetyltransferase activity in rat lens.

Activity of serotonin N -acetyltransferase (NAT), a key regulatory enzyme in melatonin biosynthesis, was detected in the rat lens. NAT activity in the lens showed significant diurnal variation in vivo and in vitro, peaking during the period of darkness, when the lenses were maintained under 14 hr light/10 hr dark cycle. Cultured lenses exhibited a circadian rhythm of NAT activity when maintained under constant darkness. However, the rhythm in vitro was not entrained when the light/dark cycle was delayed 8 hr from the cycle in intact animals. These data strongly suggest that the rat lens contains a circadian clock that controls NAT activity, although the circadian clock appears to lack a photic entrainment mechanism.

Animals↗
PubMed2000

Clinical use of lidocaine for control of stroke oedema in the posterior cranial fossa accompanied by acute hydrocephalus.

Intravenous Lidocaine, in combination with steroid and Mannitol was used in 17 critical cases to control posterior fossa stroke oedema with jeopardised upward or downward herniation. Lidocaine successfully provided time for observation to select 5 correct candidates out of 17, indicated for aggressive decompression surgery in addition to ventricular drainage for acute hydrocephalus. There is no 'Golden-Rule' for this situation but the use of Lidocaine has a place in the management of it.

Aged↗
PubMed2000

Development of monocrotaline-induced pulmonary hypertension is attenuated by a serotonin receptor antagonist.

The significance of serotonin in the pathogenesis of monocrotaline-induced pulmonary hypertension (MCT-PH) in rats, plasma serotonin concentrations, and the effect of a serotonin receptor antagonist administration in association with the number of proliferative cells were investigated. The thickness of the media of the small pulmonary arteries and the weight ratio of the RV to that of LV + S (RV/[LV + S] weight ratio) were used as indices of the severity of PH. Plasma serotonin concentrations were measured by high-performance liquid chromatography. Histopathologic analysis of the lung tissue was performed by hematoxylin-eosin and elastin van Gieson staining. Immunohistopathologic staining for proliferating cell nuclear antigen (PCNA) was performed to identify proliferative cells. The severity of PH as determined by the medial thickness of the small pulmonary arteries and RV/(LV + S) weight ratio in rats with MCT-PH was significantly reduced after treatment with MCI-9042 (p < 0.01 and p < 0.05, respectively). The serotonin concentration was significantly greater in MCT-PH rats than in normal control rats (p < 0.05). The scores for histopathologic changes, such as thickening of the alveolar walls and interstitial inflammatory cell infiltration in MCT-PH rats, were significantly reduced after treatment with MCI-9042 (p < 0.05 and p < 0.01, respectively). The number of PCNA-positive cells was significantly greater in MCT-PH rats than in normal control rats (p < 0.0001) and was reduced after treatment with MCI-9042 (p < 0.0001). Treatment with MCI-9042 significantly inhibited the development of MCT-PH along with a decrease in the number of PCNA-positive cells, suggesting a pivotal role of serotonin in the development of PH induced by MCT.

Animals↗
PubMed2000

Anti-cathepsin G antibodies in the sera of patients with ulcerative colitis.

The presence of perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCAs) and that of antibodies against cathepsin G, a target antigen for P-ANCAs, was determined in the sera of patients with ulcerative colitis (UC), relative to the endoscopic severity and disease activity. P-ANCAs were detected by indirect immunofluorescent assay (IIF) on ethanol-fixed human neutrophils. Antibodies to cathepsin G were detected by an enzyme-linked immunosorbent assay (ELISA) and Western blotting. P-ANCAs were detected by IIF in 62.5% of 32 patients with active UC. Anti-cathepsin G antibodies were detected in 40.6% of 32 patients with active UC, and their prevalence was significantly higher in patients with severe colitis, as determined by endoscopy, than in those with mild or moderate colitis (P < 0.05). The prevalence and titers of anti-cathepsin G antibodies were significantly higher during the active than the inactive phase of the disease (P < 0.05). Measurement of titers of anti-cathepsin G antibodies by ELISA in the serum is useful for evaluating the activity of UC.

Adolescent↗
PubMed2000

Significance of low mRNA levels of interleukin-4 and -10 in mononuclear cells of the synovial fluid of patients with rheumatoid arthritis.

Our objective was to investigate the clinical significance of Th1 and Th2-type cytokines, such as interferon-gamma (IFNgamma) interleukin (IL)-12, IL-4 and IL-10, in the mononuclear cells (MNC) of the synovial fluid (SF) in patients with rheumatoid arthritis (RA). The cytokine production in the MNC obtained from the SF (SF-MNC) in 30 patients with RA and 10 with gout was examined by measuring the mRNA levels of IFNgamma, IL-12, IL-4 and IL-10 by semiquantitative RT-PCR. The mRNA levels of IFNgamma, IL-4 and IL-10 were significantly higher in the SF-MNC of RA patients than in those of gout patients (p<0.001, p<0.01 and p<0.001, respectively). Correlations between mRNA levels were significant for IL-12 and IL-4, IL-12 and IL-10, and IL-4 and IL-10 (p<0.05). The mRNA levels of IL-4 and IL-10 were very low compared to those of IL-12 in seven of the 30 patients with RA; all of these patients were in stage 4, and serum levels of CRP, ESR and blood platelet count which are considered as indices of the severity of inflammation, were significantly elevated in these seven patients compared to the other 23 RA patients. The markedly reduced synthesis of both IL-4 and IL-10 mRNA could be considered to be related to the progression and/or activity of RA. The results of this study therefore indicate an imbalance in the levels of Th1 and Th2 cytokines at the site of inflammation in RA, and draw attention to the possibility of treatment of progressive or intractable RA with IL-4 and/or IL-10.

Adult↗