Search PubMed⌕ Search

Biomedical subjects

A Matsuda

Publications and source records attributed to A Matsuda.

At least 217 records · Page 12Linked to original sources
PubMed1996

New neplanocin analogues. 6. Synthesis and potent antiviral activity of 6'-homoneplanocin A1.

The design, synthesis, and antiviral activities of 6'-homoneplanocin A (HNPA, 3) and its congeners having nucleobases other than adenine, such as 3-deazaadenine (4), guanine (5), thymine (6), and cytosine (7), were described. Starting from the known cyclopentenone derivative 8, the optically active (mesyloxy)cyclopentene derivative 15 was prepared, which was condensed with nucleobases then deprotected to give target compounds 3-7. Of these compounds, HNPA showed an antiviral activity spectrum that was comparable to, and an antiviral specificity that was higher than, that of neplanocin A. HNPA proved particularly active against human cytomegalovirus, vaccinia virus, parainfluenza virus, vesicular stomatitis virus, and arenaviruses, which is compatible with an antiviral action targeted at S-adenosylhomocysteine hydrolase. HNPA appears to be a promising candidate drug for the treatment of these viruses.

Adenosine↗
PubMed1996

Identification and immunohistochemical localization of macrophage migration inhibitory factor in human cornea.

We identified macrophage migration inhibitory factor (MIF) mRNA expression in human cornea, and demonstrated its immunohistological localization. Reverse transcription-polymerase chain reaction analysis revealed that MIF mRNA was expressed in both the corneal epithelial and endothelial cells. Immunohistochemical study using the polyclonal antibody prepared from immunizing a rabbit with human recombinant MIF showed that MIF was present in the basal cells of corneal epithelium and endothelial cells. The fact that MIF exists in those cells of the cornea indicates that MIF may play an important role in corneal cell immunity and cellular differentiation.

Base Sequence↗
PubMed1996

Interaction of tRNA (uracil-5-)-methyltransferase with NO2Ura-tRNA.

tRNA in which uracil is completely replaced by 5-nitro-uracil was prepared by substituting 5-nitro-UTP for UTP in an in vitro transcription reaction. The rationale was that the 5-nitro substituent activates the 6-carbon of the Ura heterocycle towards nucleophiles, and hence could provide mechanism-based inhibitors of enzymes which utilize this feature in their catalytic mechanism. When assayed shortly after mixing, the tRNA analog, NO2Ura-tRNA, is a potent competitive inhibitor of tRNA-Ura methyl transferase (RUMT). Upon incubation, the analog causes a time-dependent inactivation of RUMT which could be reversed by dilution into a large excess of tRNA substrate. Covalent RUMT-NO2Ura-tRNA complexes could be isolated on nitrocellulose filters or by SDS-PAGE. The interaction of RUMT and NO2Ura-tRNA was deduced to involve formation of a reversible complex, followed by formation of a reversible covalent complex in which Cys 324 of RUMT is linked to the 6-position of NO2Ura 54 in NO2Ura-tRNA.

Binding Sites↗
PubMed1996

Cell adhesion to substratum and activation of tyrosine kinases are essentially required for G1/S phase transition in BALB/c 3T3 fibroblasts.

Cell adhesion to substratum and activation of tyrosine kinases are essential for the progression of cell cycle through G1 phase in mammalian cells. The kinetic studies of mouse BALB/c 3T3 fibroblasts showed that serum was no longer required for the progression of G1/S phase transition. In contrast, cell adhesion was essentially required in late G1 phase, especially at the period of G1/S transition. Among the kinase inhibitors used to elucidate the signal transduction caused by cell adhesion, tyrosine kinase inhibitors, genistein and herbimycin A, blocked the G1/S transition most effectively when cells were exposed to the inhibitors at the period of G1/S transition. Cell adhesion was not critically required for cells to undergo DNA synthesis once they had passed the G1/S boundary, and the effects of tyrosine kinase inhibitors on the progression of S phase were also not critical. The expressions of histone H2B and dihydrofolate reductase (DHFR) genes (S phase specific genes) and also the transcription factor E2F-1 gene (an activator of DHFR gene) were suppressed when cells were cultured without adhesion or exposed to the tyrosine kinase inhibitors. These results suggest that cell adhesion to substratum plays an important role in the G1/S phase transition of mouse BALB/c 3T3 fibroblasts through the activation of tyrosine kinases other than growth factor receptor-tyrosine kinases.

3T3 Cells↗
PubMed1996

Inactivation of inosine 5'-monophosphate dehydrogenase by the antiviral agent 5-ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide 5'-monophosphate.

Inosine 5'-monophosphate dehydrogenase (IMPDH) is the rate-limiting enzyme in de novo guanine nucleotide biosynthesis. IMPDH converts inosine 5'-monophosphate (IMP) to xanthosine 5'-monophosphate (XMP) with concomitant conversion of NAD+ to NADH. The antiviral agent 5-ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide (EICAR) is believed to inhibit IMPDH by forming an active metabolite, the 5'-monophosphate EICARMP. The experiments reported here demonstrate that EICARMP irreversibly inactivates both human type II and Escherichia coli IMPDH. IMPDH is protected from EICARMP inactivation by IMP, but not by NAD+. Further, denaturation/renaturation of the EICARMP-inactivated enzyme did not restore enzyme activity, which indicates that EICARMP forms a covalent adduct with IMPDH. EICARMP was successfully used to titrate the active sites of IMPDH; these experiments demonstrate that four active sites are present in an IMPDH tetramer. Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry of native E. coli IMPDH established that protein translation initiates at the third ATG of the DNA sequence. Thus, the E. coli IMPDH monomer is only 488 amino acids long and contains five instead of six cysteines. In addition, MALDI-TOF mass spectrometry showed that EICARMP is covalently bound to Cys-305 (Cys-331 in human type II IMPDH numbering), suggesting that Cys-305 functions as a nucleophile in the IMPDH reaction. The inactivation of the E. coli enzyme is a single-step reaction with kon = 1.94 x 10(4) M-1 s-1. In contrast, the inactivation of human type II IMPDH involves a two-step mechanism where Ki = 16 microM, k2 = 2.7 x 10(-2) s-1 and kon = 1.7 x 10(3) M-1 s-1. These results demonstrate that significant differences exist between bacterial and human IMPDH and suggest that this enzyme may be a target for antibiotic drugs.

Amino Acid Sequence↗
PubMed1996

Synthesis and antiviral activity of 5-substituted (2'S)-2'-deoxy-2'-C-methylcytidines and -uridines.

Synthesis of several 5-substituted (2'S)-2'-deoxy-2'-C-methylcytidines (8) and -uridines (6, 11) has been accomplished using radical deoxygenation of the 2'-tert-alcohols via their methyl oxalyl esters as a key reaction. Anti-herpes simplex virus type-1 and -2, and anti-varicella-zoster virus activities of the newly synthesized nucleosides were evaluated. Among them, the 5-iodouracil derivative 6e showed the most potent activity against herpes simplex virus type-1, with an EC50 of 0.14 micrograms/mL without showing cytotoxicity up to 100 micrograms/mL, but had a weak activity against herpes simplex virus type-2 and no activity against varicella-zoster virus up to 50 micrograms/mL in vitro. Although the 5-fluorocytosine derivative 8b had a potent anti-herpes simplex virus type-1 activity (EC50 = 0.22 micrograms/mL), it was rather cytotoxic to the CCRF-HSB-2 human T-cell line (IC50 > or = 1.0 microgram/mL).

Animals↗
PubMed1996

Detection and immunolocalization of macrophage migration inhibitory factor in rat iris and ciliary epithelium.

To elucidate the role of macrophage migration inhibitory factor (MIF) in ocular inflammation, we examined the localization of MIF in the normal anterior uveal tract of rats. Immunohistochemistry using an anti-MIF antibody revealed that MIF was present in non-pigment epithelial cells of the ciliary body and the epithelial cells of the iris. Western blot analysis of these tissues showed a single band specific for MIF protein. The expression of MIF mRNA in these tissues was further confirmed by reverse transcription-polymerase chain reaction. Since MIF is known to be a potent proinflammatory cytokine, identification of the protein in iris and ciliary epithelial cells suggests the possibility that it may play an important role in ocular inflammation.

Animals↗
PubMed1996

A family with two sisters with collagenofibrotic glomerulonephropathy.

Collagenofibrotic glomerulonephropathy is a recently recognized disease entity. Although an autosomal recessive inheritance pattern has been suggested for this condition, there are few reports of familial cases. Only four pairs of child siblings, with histological confirmation of the glomerular lesions, have been reported. The current report describes a family including two sisters with histological evidence of collagenofibrotic glomerulonephropathy. Serum concentrations of the procollagen III peptide were elevated in the affected sisters, whereas their parents and other siblings demonstrated neither proteinuria nor increased blood levels of the procollagen III peptide. Our findings support an autosomal recessive pattern of inheritance for this type of glomerulonephropathy. They also suggest that the serum concentration of the procollagen III peptide is a useful marker for collagenofibrotic glomerulonephropathy.

Adult↗
PubMed1996

Alterations in activity of protein tyrosine phosphatase SH-PTP1 in autoimmune MRL/mpj-lpr/lpr mice.

Activities of protein tyrosine kinase (PTK) and protein tyrosine phosphatase (PTP) in autoimmune MRL/MpJ-lpr/lpr mice (lpr mice) were measured and compared with the activities in the tissues from MRL/MpJ-+/+ mice (+/+ mice) as the control. In the spleen and liver, PTK activities in cytosol and membrane fractions were about 1.7- and 1.3-fold, respectively, higher in lpr mice than +/+ mice. PTP activities in cytosol and membrane fractions from lpr mice were 1.7- and 1.3-fold, respectively, higher in spleen, and 2.5- and 1.3-fold, respectively, higher in liver compared with those of the controls. These results demonstrate that the mutation of lpr gene resulted in elevation of PTK and PTP activities. Then, we measured the amounts and activities of SH-PTP1, a cytosolic PTP playing a crucial role in intracellular signaling from Fas antigen. The amounts of SH-PTP1 were about 4-fold larger in thymus, spleen, and lymphnodes than in liver, but there was no marked difference in the amounts between lpr and +/+ mice. On the other hand, activity of SH-PTP1 was definitely lower in lpr spleen and lymphnodes than +/+ spleen, but several times higher in lpr liver than +/+ liver. Tyrosine phosphorylation levels of SH-PTP1 in spleen of lpr and +/+ mice were similar. However, in liver, it was less phosphorylated in lpr than in +/+ mice. This hypophosphorylation might cause the activation of SH-PTP1 activity in lpr liver.

Animals↗
PubMed1996

In vitro and in vivo antitumor activity of a novel nucleoside, 4'-thio-2'-deoxy-2'-methylidenecytidine.

The in vitro and in vivo antitumor activity of a novel nucleoside, 4'-thio-2'-deoxy-2'-methylidenecytidine (4'-thio-DMDC), was examined. 4'-Thio-DMDC inhibited the growth of various cell lines established from human solid cancers, particularly the growth of lung and bladder carcinomas and melanomas. 4'-Thio-DMDC exhibited potent antitumor activity against subcutaneously implanted murine sarcoma S-180 and human fibrosarcoma HT-1080 xenografts. It was shown that 4'-thio-DMDC suppressed cell growth by inhibiting cellular DNA synthesis, and phosphorylation of the 5'-position of its deoxyribose by deoxycytidine kinase was needed for its antitumor activity. 4'-Thio-DMDC is a poor substrate for cytidine deaminase, thus it is a promising agent for the treatment of malignant solid tumors because it will not be converted into its inactive uridine form.

Animals↗
PubMed1996

Effects of omega-conotoxin GVIA on the activation of capsaicin-sensitive afferent sensory nerves in guinea pig airway tissues.

We examined the effects of Ca2+ channel antagonists on various respiratory reactions induced by the activation of capsaicin-sensitive afferent sensory nerves. Intravenous (i.v.) injection of the N-type Ca2+ channel antagonist omega-conotoxin GVIA (CgTX) (1-20 micrograms/kg) dose-dependently inhibited capsaicin-induced guinea pig bronchoconstriction, whereas i.v. administration of the L-type antagonist nicardipine (100 micrograms/kg), the P-type antagonist omega-agatoxin IVA (AgaTX) (20 micrograms/kg) or the OPQ family-type antagonist omega-conotoxin MVIIC (CmTX) (20 micrograms/kg) had no effect. However, CgTX (20 micrograms/kg) failed to inhibit substance P-induced guinea pig bronchoconstriction. CgTX (20 micrograms/kg) significantly inhibited cigarette smoke-induced guinea pig tracheal plasma extravasation, but not the substance P-induced reaction. CgTX also reduced electrical field stimulation-induced guinea pig bronchial smooth muscle contraction (0.01-10 microM) and capsaicin-induced substance P-like immunoreactivity release from guinea pig lung (0.14 microM). This evidence suggests that N-type Ca2+ channels modulate tachykinin release from capsaicin-sensitive afferent sensory nerve endings in guinea pig airway tissue.

Animals↗
PubMed1996

Characterization of dextran sulfate-induced guinea pig tracheal plasma extravasation.

We examined the effect of dextran sulfate on guinea pig tracheal vascular permeability. I.v. injection of dextran sulfate (10-100 mg/kg) with captopril (1 mg/kg) induced guinea pig tracheal plasma extravasation. The i.v. administration of bradykinin (0.8-8 micrograms/kg) with captopril (1 mg/kg) also induced plasma extravasation. Bradykinin B2 antagonists, D-Arg[Hyp3-Thi5-D-Tic7-Tic8]-bradykinin (NPC 16731) and D-Arg[Hyp3-Thi5-D-Tic7-Oic8]-bradykinin (Hoe 140), reduced both dextran sulfate (32 mg/kg)- and bradykinin (2.5 micrograms/kg)-induced tracheal plasma extravasation in a dose-dependent manner. However, a cyclooxygenase inhibitor, indomethacin (1 mg/kg), and a neurokinin antagonist, [N-[N2-[N-[N-[N-[2,3-didehydro-N-methyl-N-[N-[3-(2-pentylphenyl )- propionyl]-L-threonyl]tyrosyl-L-leucynyl]-D-phenylalanyl]-L-a llo-threonyl]-L-asparaginyl]-L-serine-D-lactone] (FK 224) (1 mg/kg), had no effect on tracheal plasma extravasation induced by dextran sulfate and bradykinin. Dextran sulfate (32 mg/kg) with captopril (1 mg/kg) greatly increased the bradykinin level in guinea pig plasma. This evidence suggests that dextran sulfate releases bradykinin in guinea pig plasma and causes guinea pig tracheal plasma extravasation via the activation of bradykinin B2-receptors.

Analysis of Variance↗
PubMed1996

Damage induced by hydroxyl radicals generated in the hydration layer of gamma-irradiated frozen aqueous solution of DNA.

Aqueous DNA solutions with or without the spin trap alpha-phenyl-N-tert-butylnitrone (PBN) were exposed to gamma-rays at 77 K. After thawing the solutions, three experiments were carried out to confirm the generation of OH radicals in the hydration layer of DNA and to examine whether they act as an inducer of DNA strand breaks and base alterations. Observation with the ESR-spin trapping method showed ESR signals from PBN-OH adducts in the solution containing PBN and DNA, but there were few signals in the solution containing PBN alone, suggesting that reactive OH radicals were produced in the hydration layer of gamma-irradiated DNA and were effectively scavenged by PBN, and that unreactive OH radicals were produced in the free water layer of gamma-irradiated DNA. Agarose gel electrophoresis of DNA proved that PBN had no effect on the formation of strand breaks, whereas examination with the high-performance liquid chromatography-electrochemical detection (HPLC-ECD) method showed that PBN suppressed the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG). From these results it was concluded that OH radicals generated in the hydration layer of gamma-irradiated DNA did not induce DNA strand breaks but induced base alterations.

Animals↗
PubMed1996

Primary aldosteronism with bilateral multiple aldosterone-producing adrenal adenomas.

A 41-year-old woman developed primary aldosteronism due to bilateral multiple aldosterone-producing adenomas (APA). She was suspected to have idiopathic hyperaldosteronism (IHA) 7 years previously. Although preoperative data suggest APA and IHA was suspected in a postoperative microscopic specimen, a definite clinical diagnosis could not be made. Cytochrome P-450 and other enzymes involved in aldosterone synthesis were found in the tumor portions but not in the zona glomerulosa of attached adrenals, which histopathologically showed "paradoxical hyperplasia". This was a rare case of bilateral multiple APA, which could be differentiated from IHA by immunohistochemical analysis of adrenal steroidogenic enzymes.

Adenoma↗
PubMed1996

Cytokeratin and proliferative cell nuclear antigen expression in superior limbic keratoconjunctivitis.

PURPOSE: Superior limbic keratoconjunctivitis (SLK) is a disease of unknown etiology which showed various degrees of keratinization. The cytokeratins (CKs) are known to be the hallmark of epithelial differentiations and each CK has a characteristic distribution dependent on the type and the differentiation status of epithelium. The authors have studied the expression of cytokeratins (CKs) as well as proliferating cell nuclear antigen (PCNA) in the conjunctiva of SLK. METHODS: Three superior limbic conjunctivae of patients with SLK and two normal conjunctivae were examined immunohistochemically using monoclonal antibodies against CKs and PCNA. RESULTS: In SLK conjunctivae, increased expression of a basal cell marker (CK14) was observed throughout the epithelium. Sporadic positive staining with CK10, which is a specific marker for keratinization, was correlated to the severity of the disease. The disappearance of CK13 staining, the marker for nonkeratinized stratified epithelia, at the basal cell layer of SLK was noted. Moreover, increased expression of PCNA in SLK was observed. CONCLUSIONS: The altered expression of CKs in SLK suggests an abnormality of differentiation in the conjunctival epithelium of the disease. Upregulated proliferation of conjunctival epithelial cells may be another feature of the disease.

Aged↗
PubMed1996

[Design of a new antitumor nucleoside CNDAC, against solid tumors].

The design, antitumor activity in vitro as well as in vivo, and mechanism of CNDAC have been described. CNDAC had potent antitumor effects against various solid tumors in vitro as well as in vivo. CNDAC was phosphorylated by deoxycytidine kinase, followed by certain nucleotide kinases to afford its 5'-triphosphate (CNDACTP), which was a potent inhibitor of DNA polymerase alpha. Using a chain-extension method with Vent (exo-) DNA polymerase and a short primer/template system, we found that CNDACTP was incorporated into the primer. After further chain-extension reaction of the primer containing CNDAC at the 3'-terminus, chain elongation was not observed. Therefore, CNDACTP appeared to act as a chain-terminator. Analyses of the structure of the 3'terminus in the primer revealed the presence of ddCNC together with CNDAC and CNDC. The existence of ddCNC in the 3'-end of the primer would be due to the self-strand-break by the nucleotide incorporated next to CNDAC.

Antineoplastic Agents↗
PubMed1996

[Refractory anemia with excess of blasts (RAEB) with a high level of HbF that preceded apparent pancytopenia].

A 76-year-old male was kept under observation for idiopathic interstitial peumonitis in our hospital from August 1992. Laboratory data revealed a slightly high level of HbF (2.7%) but normal values of other hematological examination. The level of HbF increased slowly, and in April 1994, pancytopenia appeared for the first time. Bone marrow was normocellular with myelodysplasia and 9% blasts. Cytogenetic analysis revealed 46, XY, del (20) (q11;q13). He was diagnosed as having myelodysplastic syndrome (MDS), refractory anemia with excess of blasts. At diagnosis of MDS, the level of HbF was 20.0%. He developed acute myelocytic leukemia 3 months later. It has been reported that approximately 40% of patients with MDS have higher HbF levels than normal, which is considered to be functional abnormality of the MDS clone. It is suggested that the MDS clone had already increased in this patient at presentation, 32 months before pancytopenia appeared.

Aged↗