Search PubMed⌕ Search

Biomedical subjects

M Matsuda

Publications and source records attributed to M Matsuda.

At least 19 recordsLinked to original sources
PubMed1992

Reversible interactions between plasminogen activators and plasminogen activator inhibitor-1.

We have shown that the urokinase (UK) kringle domain contains a high-affinity plasminogen activator inhibitor-1 (PAI-1) binding site, responsible for the 10-fold faster complex formation between UK and PAI-1 than between PAI-1 and low-molecular-weight urokinase (LMWUK). Complex formation between UK and PAI-1, but not between LMWUK and PAI-1, was suppressed 10-fold in the presence of peptide U-107 derived from the UK kringle domain. Peptide U-373 derived from the UK catalytic domain slowed complex formation between UK and PAI-1 and also LMWUK and PAI-1. Inactivation of tissue-type plasminogen activator (tPA) by PAI-1 was slowed 10-fold in the presence of peptides derived from the tPA finger and kringle-2 domains. DFP-inactivated (DIP) UK and both forms of DIP-tPA inhibited PAI-1 binding to U-107 and to U-373 whereas single-chain urokinase-type PA (scuPA) was unable to compete with either peptide for PAI-1 binding. These data suggest that the reversible PAI-1 binding site in the UK A-chain plays a role in the rapid association with PAI-1 as important as those that reside in the tPA A-chain and that reversible PAI-1 binding sites are expressed on the surface of UK upon conversion from scuPA, in contrast to tPA.

Amino Acid Sequence↗
PubMed1992

Studies on pyridonecarboxylic acids. 1. Synthesis and antibacterial evaluation of 7-substituted-6-halo-4-oxo-4H-[1,3]thiazeto[3,2-a]quinoline-3- carboxylic acids.

A series of [1,3]thiazeto[3,2-a]quinoline-3-carboxylic acids and their esters were prepared and evaluated for antibacterial activity. The derivatives with a hydrogen or methyl group at C-1, fluorine at C-6, and piperazinyl or 4-methyl-1-piperazinyl group at C-7 showed superior in vitro antibacterial activity, and the derivatives with 4-methyl-1-piperazinyl group at C-7 had potent in vivo activity. Compound 29a (NM394) showed excellent in vitro antibacterial activity and low toxicity but poor absorption from the gastrointestinal tract. Compound 29ee (NM441), an N-[(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl] derivative of 29a, was found to possess a favorable pharmacokinetic profile and oral activity superior to that of ciprofloxacin in experimental animals.

Administration, Oral↗
PubMed1992

Heterozygous abnormal fibrinogen Osaka III with the replacement of gamma arginine-275 by histidine has an apparently higher molecular weight gamma-chain variant.

Congenitally abnormal fibrinogen Osaka III with the replacement of gamma Arg-275 by His was found in a 38-year-old female with no bleeding or thrombotic tendency. Release of fibrinopeptide(s) by thrombin or reptilase was normal, but her thrombin or reptilase time in the absence of calcium was markedly prolonged and the polymerization of preformed fibrin monomer which was prepared by the treatment of fibrinogen with thrombin or reptilase was also markedly defective. Propositus' fibrinogen had normal crosslinking abilities of alpha- and gamma-chains. Analysis of fibrinogen chains on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) in the system of Laemmli only revealed the presence of abnormal gamma-chain with an apparently higher molecular weight, the presence of which was more clearly detected with SDS-PAGE of fibrin monomer obtained by thrombin treatment. Purified fragment D1 of fibrinogen Osaka III also seemed to contain an apparently higher molecular weight fragment D1 gamma remnant on Laemmli gels, which was digested faster than the normal control by plasmin in the presence of [ethylenebis(oxyethylenenitrilo)]tetraacetic acid (EGTA).

Adult↗
PubMed1992

Delta-thalassemia caused by disruption of the site for an erythroid-specific transcription factor, GATA-1, in the delta-globin gene promoter.

Delta-thalassemia is a complex group of inherited disorders of globin genes characterized by impaired synthesis of the delta-globin chain. The T-C substitution was detected at position -77 of the delta-globin gene isolated from three independent Japanese individuals who were homozygotes for delta-thalassemia. To elucidate the significance of the mutation in delta-globin gene expression, we investigated the genotype of three delta-thalassemia homozygotes and 58 normal individuals using dot blot hybridization of the polymerase chain reaction (PCR)-amplified DNA. The mutation was observed in six alleles of three homozygotes, while no mutation was detected in 116 alleles of normal individuals, thereby indicating the close association of this mutation with the thalassemia phenotype. Since the mutation (TTATCT-TCATCT) is located within the inverted binding motif of GATA-1 (T or A-G-A-T-A-G or A), an erythroid cell-specific transcription factor, we did gel retardation assays using nuclear extracts from the erythroid cells. We found that GATA-1 binds the oligonucleotide spanning positions -61 to -90, but does not bind to the oligonucleotide with the mutation at position -77. Competition gel retardation assays showed that GATA-1 binding can be competed out by the fragment with the GATA-1 motif, but not with the mutant oligonucleotide. Analysis of the transient expression of the CAT gene linked to the delta-globin gene promoter region demonstrated that the construct with the mutant promoter region was expressed about 20-fold less compared with the normal one. Thus, the mutation at position -77 impairs delta-globin gene expression by abolishing GATA-1 binding to the AGATAA sequence of the promoter region of the delta-globin gene. This provides a good example of involvement of tissue-specific transacting factors in the molecular pathogenesis of hereditary diseases.

Base Sequence↗
PubMed1992

Calmodulin is involved in catecholamine secretion from digitonin-permeabilized bovine adrenal medullary chromaffin cells.

The role of calmodulin in exocytotic secretion was studied using digitonin-permeabilized bovine adrenal medullary chromaffin cells. Addition of calmodulin to the permeabilized cells increased Ca(2+)-dependent norepinephrine release in a dose-dependent manner. Unlike calmodulin, addition of caldesmon, actin or bovine serum albumin did not increase the release. Calmodulin increased the release at Ca2+ concentrations of more than 10(-6) M and its effect increased with increase in Mg2+ concentration. Th release of norepinephrine enhanced by calmodulin was inhibited by tetanus toxin, which specifically inhibits exocytotic secretion. These results indicate directly that calmodulin plays an important role in exocytotic secretion from chromaffin cells.

Actins↗
PubMed1992

Nonrandom distribution of gp120 N-linked glycosylation sites important for infectivity of human immunodeficiency virus type 1.

More than 20 consensus N-linked glycosylation sites occur in the gp120 coding sequence of most isolates of human immunodeficiency virus type 1. Based on the N-linked glycosylation pattern of a well-characterized recombinant gp120, it is likely that N-linked sugars are present at most, if not all, of the consensus glycosylation sites of the heavily glycosylated gp120. In this study, we evaluated the relative importance of each of the 24 N-linked glycosylation sites of gp120 in the molecular clone HXB2 to viral infectivity. The ability of HXB2-derived mutants, each having 1 of the 24 N-linked glycosylation sites mutated by site-directed mutagenesis, to infect CD4-positive SupT1 cells was compared with that of the wild-type virus. We found that most of the individual consensus N-linked glycosylation sites are dispensable for viral infectivity. The five consensus N-linked glycosylation sites that are likely to have important roles in infectivity are all located in the amino-terminal half of gp120, indicating that the N-linked glycosylation sites that are important for infectivity of human immunodeficiency virus type 1 are not randomly distributed in gp120. We predict that a partially glycosylated gp120 with most of the dispensable N-linked glycosylation sites removed may be a better vaccine candidate than the fully glycosylated gp120.

Amino Acid Sequence↗
PubMed1992

Clinical and histopathologic evaluation of the expression of Ha-ras and fes oncogene products in lung cancer.

The expression of Ha-ras and fes oncogenes was investigated with the immunohistochemical method in formalin-fixed, paraffin-embedded tissue specimens of 147 lung carcinomas. Positive immunoperoxidase reactions for Ha-ras p21 were found in 80.5% of the adenocarcinomas, 39.5% of the squamous cell carcinomas, 21.4% of the large cell carcinomas, and 15.4% of the small cell carcinomas; those for fes P85 were found in 51.2% of the adenocarcinomas, 26.3% of the squamous cell carcinomas, 35.7% of the large cell carcinomas, and 15.4% of the small cell carcinomas. Both Ha-ras p21 and fes P85 were expressed most frequently and most strongly in adenocarcinoma. In addition, adenocarcinoma showed significantly higher incidence of concomitant expression of Ha-ras p21 and fes P85 as compared with other histologic types of lung cancer. Thus, the authors suggest that the cooperative effects of Ha-ras and fes oncogenes are especially important in the carcinogenesis of adenocarcinoma. In adenocarcinoma, the incidence and grade of Ha-ras p21 expression increased with the degree of histologic differentiation, suggesting that Ha-ras oncogene might be related to cellular differentiation. Papillary adenocarcinoma showed more frequent Ha-ras p21 expression in comparison with acinar adenocarcinoma. In well- or moderately differentiated adenocarcinoma, the incidence and grade of Ha-ras p21 immunoreactivity in the cases with poor prognosis were significantly higher than in those with good prognosis if other major prognostic factors were equivalent in the two groups. The authors propose that the expression of Ha-ras p21 may be one of the useful prognostic factors in such carcinomas.

Adenocarcinoma↗
PubMed1992

Craniosynostosis in association with medulloblastoma.

A case of a 13-month-old boy with craniosynostosis associated with medulloblastoma was presented. Sagittal suture was prematurely closed, and coronal and lambdoid sutures were widely separated. A large infiltrative tumor in the midcerebellar region was partially removed and treated by irradiation and chemotherapy. A review of the current literature failed to reveal a similar report.

Cerebellar Neoplasms↗
PubMed1992

Characterization of an abnormal fibrinogen Osaka V with the replacement of gamma-arginine 375 by glycine. The lack of high affinity calcium binding to D-domains and the lack of protective effect of calcium on fibrinolysis.

Prolonged thrombin time was completely corrected by the addition of millimolar concentrations of calcium in a new abnormal fibrinogen, Osaka V. Analysis of lysyl endopeptidase digests of A alpha-, B beta-, or gamma-chains by high performance liquid chromatography, and the following amino acid sequence analysis of relevant peptides revealed that about 50% of the gamma-chain has a replacement of gamma-arginine 375 by glycine. When fibrinogen was digested with plasmin in the presence of millimolar concentration of calcium, the amount of fragment D1 was about 50% of the normal control, and the rest was further cleaved to fragment D2, D3, or D62 with an apparent Mr of 62,000. Plasmic digestion of cross-linked fibrin in the presence of calcium resulted in the appearance of an abnormal fragment with an apparent Mr of 123,000 as well as fragments D2, D3, and D62, concomitant with the decrease of D dimer. The gamma-remnant of the abnormal fragment proved to be a cross-linked complex of the normal D1 gamma-remnant and residues 374-406/411 of the abnormal gamma-chain. The number of high affinity Ca(2+)-binding sites for the normal fibrinogen and fibrinogen Osaka V obtained by equilibrium dialysis was 2.88 (about 3) and 1.85, respectively, and that for the abnormal molecules was calculated as 0.9 (about 1) from their relative amounts in the samples, suggesting the lack of two Ca(2+)-binding sites in the D-domains. These data suggest that the normal structure of the COOH-terminal portion of the gamma-chain including residue 375 is required for the full expression of high affinity calcium binding to D-domains, the ability to be protected by calcium against plasmic digestion, and fibrin polymerization. During these studies, we found that the NH2-terminal amino acid of the gamma-remnant in fragments D or D dimer which were obtained after prolonged digestion with plasmin is gamma-Met89.

Adult↗
PubMed1992

Survival for clinical stage I lung cancer not surgically treated. Comparison between screen-detected and symptom-detected cases. The Japanese Lung Cancer Screening Research Group.

To assess the extent of overdiagnosis bias in lung cancer screening, clinical Stage I lung cancer cases detected by chest radiograph examination, with histologic or cytologic evidence of malignancy and not treated by surgical operation, were followed up for more than 10 years. Of 1297 screen-detected and 1297 symptom-detected cases collected from 20 institutions, 42 screen-detected and 27 symptom-detected cases satisfied the study criteria. In about half of the cases, the patients had no contraindication for surgical treatment, but they refused surgical procedure. All such patients from the screen-detected and symptom-detected groups died within 122 and 67 months, respectively, of diagnosis. Among the screen-detected and symptom-detected cases, 80% and 81%, respectively, of the patients died of lung cancer. The median survival time was 25 and 13 months for those in the screen-detected and symptom-detected groups, respectively. The difference in survival was statistically significant between the two groups, which indicated the effect of lead time and length-biased sampling. Analysis of the causes of death other than lung cancer showed that there was no difference in the observed cumulative rates of deaths of other causes between the two groups, and these figures were almost the same as those expected from the general population. This indicates that overdiagnosis bias would be minimal in screen-detected lung cancer cases detected by chest radiograph examination.

Aged↗
PubMed1992

[Growth of the graft and astrocytic reaction following transplantation of fetal brain to adult rat's brain. Part I: Tissue transplantation into cerebral cortex, lateral ventricle, subarachnoid space and cerebral cortical cavity].

Brain transplantation has been examined as one of the therapeutic methods in the animal models of Alzheimer's disease. Among a lot of problems inherent to therapeutic brain transplantation, we have investigated implanting techniques and methods. Small pieces of fetal basal forebrain tissue containing cholinergic neurons were transplanted into adult rats' cerebral cortex, lateral ventricle, subarachnoid space, and the cerebral cortical cavity which had been made 10 days before transplantation (delayed cavity technique). Two to 3 months after transplantation, growth of the grafts, neurites elongation and astrocytic reaction were observed by Nissl staining, histochemical staining for acetylcholinesterase and immunocytochemical staining for glial fibrillary acidic protein (GFAP). Intracortical grafts were small and surrounded by thick glial scar formation, but there was found a partial lack of glial scar and host-graft neuronal integration was also observed. Both intraventricular and subarachnoid grafts grew relatively well. GFAP-immunoreactive cells had a tendency to gather near the margin of the graft and perivascularly. These facts seemed to suggest that reactive astrocytes were also taking part in support of the homeostasis of environments in the graft tissue. By delayed cavity technique, better growth of the grafts was observed, but dense glial and connective tissue scar tissues developed and prevented the outgrowth of neuronal processes. Nevertheless, hyperinnervation from graft to host cortex was partially noticed. It should be stressed that although the hyperinnervation may be effective for recovery of the host from the central nervous system damages, it may possibly damage the host's neuronal circuits.

Animals↗
PubMed1992

[Growth of the graft and astrocytic reaction following transplantation of fetal brain to adult rat's brain. Part II: Cell suspension transplantation into the subarachnoid space].

Suspensions of basal forebrain cells of fetal rats were transplanted into the subarachnoid space of adult rats through a microsyringe needle which was transcortically inserted to the subarachnoid space. Two to 3 months after the transplantation, growth of the graft, neuritic elongation, neovascularization, and astrocytic reaction were examined by Nissl staining, histochemical staining for acethylcholinesterase and Klüver-Barrera's myelin staining, vascular relief images and immunohistochemical staining for laminin, and immunocytochemical staining for glial fibrillary acidic protein (GFAP). Transplanted fetal neurons survived and grew very well over the brain surface and exhibited facilitated neuritic elongation. Several bundles of myelinated fibers linking the subarachnoid and the subpial grafted cells were noticed, but the myelinated fibers penetrating the intact pia mater were not verified. In the grafted tissue, extracellular matrix was formed and a lot of small vessels and capillaries were noticed. Many GFAP-immunoreactive cells were seen in the graft. They had a tendency to gather perivascularly and near the margin of the graft tissue facing subarachnoid space. The subarachnoid space is thought to be an adequate place for transplanted neuronal and glial cells to grow. The subarachnoid space contains the cerebrospinal fluid and also it contacts with rich pial vessels, so that it seems to be superior to the intraparenchymal area in respects of a supply of oxygen and nutrition and of low tissue pressure. Transplanted tissue may be supposed to work as the exocrine and/or endocrine organ which secretes neurotransmitters and their synthetic enzymes and neurotrophic factors. If this is true, it would imply that the subarachnoid space is considered as a promising site for implantation.

Animals↗
PubMed1992

Subcellular distribution of ubiquitin-protein conjugates in the hippocampus following transient ischemia.

Ubiquitin-protein conjugates in the hippocampus were analyzed by immunoblotting with a monoclonal anti-ubiquitin antibody. In the CA1 region, Triton X-100 insoluble ubiquitin-protein conjugates increased after 24 hr following 20 min of ischemia. When the total hippocampi were fractionated subcellularly, ubiquitin-protein conjugates increased in the particulate, especially in the mitochondrial fraction. The ubiquitin-protein conjugates were solubilized by SDS, or were partially solubilized by urea. The results indicate that insoluble ubiquitin-protein conjugates increase after ischemia.

Animals↗
PubMed1992

Inhibition of cephalic neural tube closure by 5-azacytidine in neurulating rat embryos in vitro.

Head-fold stage rat embryos (9.5 days of gestation) were cultured for 48 h in rat serum with or without 0.8 microM 5-azacytidine. Incomplete closure of the cephalic neural tube was observed in 5-azacytidine-treated embryos cultured for 48 h (25-somite stage). Control embryos showed complete fusion of cephalic neural folds at 33 h (16-somite stage) in culture. Drug administration or removal experiments revealed that embryos were sensitive to 5-azacytidine during 6-12 h of culture (three to five somite stages). Electron microscopical studies indicated that the arrangement and fine structure of cephalic neuroepithelial cells were almost the same in control and treated embryos. There was no significant difference in DNA and protein contents between control and treated embryos cultured for 36 h. Immunocytochemical observations using 5-methylcytosine-specific antibody revealed that the staining of neuroepithelial cells in the median part of the transversely sectioned cephalic neural plate, and of mesenchymal cells near the apices of the plate, was suppressed by 5-azacytidine. These results suggest that DNA methylation of these cells plays an important role in closure of the cephalic neural tube.

5-Methylcytosine↗
PubMed1992

Developmental change of an enzyme activity oxidizing gamma-aminobutyraldehyde to gamma-aminobutyric acid in the chick embryonic brain.

An enzyme activity oxidizing gamma-aminobutyraldehyde (ABAL) to GABA reflecting an alternative pathway for GABA synthesis was assayed in the developing chick embryonic brain and was compared with glutamate decarboxylase (GAD) activity. An enzyme activity oxidizing ABAL to GABA showed almost constant level during development in the chick embryonic brain, and was present at low levels compared with GAD activity. The results indicate that GABA synthesis via an alternative pathway is always much less than synthesis via the GAD-dependent pathway in the developing chick embryonic brain.

Aldehydes↗