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Biomedical subjects

M Tsuda

Publications and source records attributed to M Tsuda.

At least 325 records · Page 18Linked to original sources
PubMed1993

A study on gamma-aminobutyric acid (GABA) and its analogues by using molecular orbital methods: on epileptogenicity of new quinolones.

Using the molecular orbital methods, we examined molecular structure, electron density distribution, electrostatic potential field and receptor structure of gamma-aminobutyric acid (GABA), and its analogues. The following findings were obtained: a comparison of the biological activity and the morphology electrostatic potentials of GABA analogues disclosed that the active site is the amino group, and the biological activity correlates closely with the electrostatic potential structure around the amino group. The active sites were compared between the receptor-binding molecules and the GABA uptake inhibitory molecules, and the results suggested that the receptor structure differed between the two groups of molecules and that the GABA A receptors had two subtypes. On these results, the epileptogenicity of new quinolones was studied using this method. These results suggested that the new quinolones blockaded the GABA receptor-binding system and that the important active site of the new quinolones for GABA receptor-binding was the the piperazyl amino group. These results suggested that the concentration of zwitterion type of the new quinolones was very important clinically.

Animals↗
PubMed1993

A case of protein C deficiency associated with cerebral infarction and obstruction of deep leg and inferior mesenteric veins.

Protein C, a vitamin K-dependent protein, is a blood coagulation inhibitor. Its deficiency causes systemic thrombosis. A 31-year-old woman developed cerebral infarction followed by late psychomotor seizures, and thrombosis in the inferior mesenteric vein and bilateral crural veins. Her parents were first cousins. Her mother died of cerebral thrombosis in her 30's. Her elder brother died of suspected purpura fulminans immediately after birth. Her protein C activity and protein C antigen level decreased markedly and were less than 5% of those of normal controls and 0.3 microgram/ml, respectively. Her father, a paternal aunt and a maternal uncle also showed a low protein C activity and protein C antigen level. This patient seems to have congenital protein C deficiency which produced thrombosis in the leg veins and the mesenteric vein, probably cerebral infarction.

Adult↗
PubMed1993

Recombinant human granulocyte colony-stimulating factor therapy for cyclic neutropenia associated with common variable immunodeficiency.

A 14 year old boy with common variable immunodeficiency (CVID) had regularly recurring episodes of severe infections independently of the serum gamma-globulin level. Serial blood counts revealed that this patient also had cyclic neutropenia. Recently, recombinant human granulocyte colony-stimulating factor (rhG-CSF) was reported to be an effective treatment for this disease. We tried rhG-CSF therapy for this patient and a prompt increase in the neutrophil count was noted. However, the cyclic alterations and duration of the nadir of the neutrophil count were not altered, which suggested that rhG-CSF has a variable efficacy in at least some patients with cyclic neutropenia.

Adolescent↗
PubMed1993

Additive induction of Egr-1 (zif/268) mRNA expression in neuroblastoma x glioma hybrid NG108-15 cells via cholinergic muscarinic, alpha 2-adrenergic, and bradykinin receptors.

Administration of carbachol, noradrenaline, and bradykinin induced Egr-1 mRNA expression within 1 h in mouse neuroblastoma x rat glioma hybrid NG108-15 cells. With specific receptor antagonists, the Egr-1 inductions by carbachol and noradrenaline were shown to be mediated via cholinergic muscarinic and alpha 2-adrenergic receptors, respectively. At their saturation levels for Egr-1 induction, the two agonists had additive effects when added together, but no prolongation of the effect on Egr-1 induction was observed. Addition of carbachol or noradrenaline 6 h after primary stimulation with carbachol or noradrenaline did not result in secondary Egr-1 induction, probably because of receptor desensitization. On the other hand, bradykinin consistently had an additive effect on Egr-1 induction, irrespective of the time of its addition, suggesting that the signal pathways for Egr-1 induction by carbachol or noradrenaline and by bradykinin are different. Treatment of cells with pertussis toxin or cholera toxin strongly inhibited Egr-1 induction by carbachol or noradrenaline but only partially inhibited the induction by bradykinin. Thus, the signals transduced in NG108-15 cells by different neurotransmitter receptors appear to have different effects on Egr-1 induction, depending on the times of stimulation and the combinations of receptors stimulated.

Animals↗
PubMed1993

Analysis of intestinal flora of a patient with congenital absence of the portal vein.

A 14-year-old female patient, admitted for a closer examination of liver tumour (hepatocellular adenoma), was diagnosed as having a congenital absence of the portal vein. The blood ammonia level (approximately 120 micrograms dl-1) in the superior mesenteric vein was markedly low compared to the normal value of 300-350 micrograms dl-1 in the portal vein. The decreased ammonia concentration and urease activity of the patient's faeces were demonstrated. The dominant intestinal flora in the faeces of the patient, before operation, was Bifidobacterium sp., Bifidobacterium breve, Bifidobacterium lonqum, Lactobacillus plantarum, and after the operation Bacteroides vulgatus, Veillonella parvula, Peptococcus magnus Bifidobacterium longum. In contrast, Bifidobacterium bifidum, Bacteroides ureolyticus, Bacteroides ovatus and Bacteroides distasonis, B. ovatus, Bifidobacterium adolescentis were dominant flora in the faeces of two healthy volunteers, respectively. Among microorganisms isolated from the patient, Morganella morganii, Candida sp., Eubacterium aerofacience and Eubacterium rectale were strongly positive in urease activity in vitro; Streptococcus mitior, Staphylococcus intermedius, Micrococcus kristinae, Selenomonas ruminantum, Bacteroides ureolyticus and Lactobacillus casei ss. pseudoplantarum from the healthy volunteers. These results imply the homeostatic regulation system of faecal ammonia concentration by urease-producing microorganisms in the patient.

Adolescent↗
PubMed1993

Congenitally abnormal plasminogen in juvenile ischemic cerebrovascular disease.

BACKGROUND AND PURPOSE: Congenitally abnormal plasminogen is characterized by markedly decreased fibrinolytic activity and has been reported mainly in association with venous occlusive disease. CASE DESCRIPTION: We found three young adult patients (34, 45, and 27 years old at onset) with ischemic cerebrovascular disease, all of whom had congenital plasminogen abnormalities but no other known risk factors. Hemostatic tests of all three patients revealed plasma plasminogen activities at almost one half of the normal level despite normal plasma plasminogen antigen levels. They were found to be heterozygotes with abnormal plasminogen (normal Ala-601[GCT] to abnormal Thr-601[ACT]) by DNA sequence analysis after polymerase chain reaction. CONCLUSIONS: Congenital plasminogen abnormalities could be one of the risk factors of juvenile ischemic cerebrovascular disease of the arterial as well as venous type.

Adult↗
PubMed1993

[Gene expression and cellular function].

During the development of vertebrates, differentiated cells are already programmed to synthesize functional proteins to express their specified cellular functions by receiving several kinds of extracellular signals. By use of the in vitro and in vivo systems for analyzing the molecular mechanisms of antibody synthesis in B-lymphocytes, I have found that an activation of immunoglobulin gene could be involved in the activation of antibody synthesis induced by antigen signals. By developing the cell-free transcriptional systems of silk fibroin gene, I have subsequently found that the gene activation could mainly be achieved by the interactions between the defined nucleotide sequences located upstream from the TATA box of the gene and transcriptional factors which can specifically bind to these upstream sequences. To understand an exact role of neuronal cells in the generation of synaptic plasticity, I am now investigating the genetical responses of neuronal cells activated by synaptic transmission. Elucidation of the gene products whose expression could be affected by the synaptic transmission would reveal functional aspects of neuronal cells when they receive several kinds of synaptic inputs. By use of the primary culture of mouse cerebellar granule cells, we have already revealed several aspects of intracellular mechanisms responsible for the glutamatergic responses of the neuronal cells, focusing on an activation of transcriptional factors whose expression could be immediately induced by the glutamatergic inputs. This type of experiments would provide a valuable insight for understanding the cellular and the molecular mechanisms of synaptic plasticity.

Animals↗
PubMed1993

Blindness due to non-ketotic hyperglycinemia: report of a 38-year-old, the oldest case to date.

We report a 38-year-old woman with a mild form of hyperglycinemia complicated with optic nerve atrophy and convulsion. She was normal at birth and showed normal mental and physical development. After the age of 13, her visual acuity rapidly decreased. At the age of 33, she had numerous episodes of tonic seizures lasting for 1-2 minutes. She had optic atrophy, but no intellectual impairment. Glycine levels of the plasma, urine and cerebrospinal fluid were markedly increased, but the CSF/serum glycine ratio was slightly higher than the normal range. Although there is one case of retinal impairment of hyperglycinemia in the literature, this is the first report of blindness with hyperglycinemia in a 38-year-old woman.

Adult↗
PubMed1993

[Dermatological evaluation of a flame retardant, hexabromocyclododecane (HBCD) on guinea pig by using the primary irritation, sensitization, phototoxicity and photosensitization of skin].

As one of the projects in the safety evaluation of chemical constituents in common house-hold products, effects of hexabromocyclododecane (HBCD) were evaluated by primary skin irritation, skin sensitization, phototoxicity and photosensitization using guinea pigs. Primary skin irritation was not observed in HBCD emulsified in distilled water by the Draize test method. Skin sensitization test was carried out according to the maximization test method of Magnusson and Kligman. For this test, HBCD was dissolved in olive oil to give 5, 0.5 and 0.05%. When induction of sensitization occurred, challenged doses of 0.005, 0.05, 0.5 and 5% of HBCD (dissolved in acetone) were applied to its respective sensitized groups. The results showed that the induction dose of greater than 0.5% and the challenge dose of greater than 0.05% elicited a positive response. The increase in the concentration of induction and challenge doses did not further increase the percentage of positive response or the intensity of skin response. Phototoxicity test was carried out with 0, 0.5 and 5% of HBCD dissolved in acetone. Phototoxicity was not observed at all HBCD concentration tested. Photosensitization test was performed according to the Sato's adjuvant-strip method. The skin sensitization and challenge reaction doses were 5 and 0.5% and 0 and 0.5% HBCD (dissolved in acetone), respectively, and no positive reaction was observed. It is clear from the foregoing results that HBCD is a mild skin allergen.

Animals↗
PubMed1993

[Mitomycin C associated hemolytic uremic syndrome--a case report and review of the Japanese cases].

A 36-year-old man who developed hemolytic uremic syndrome (HUS) associated with mitomycin C (MMC) after the radical operation for early gastric cancer was reported. He was successfully treated with hemodialysis and transfusion of fresh frozen plasma. However, the pathogenesis and the effective treatment of this syndrome are still undetermined. The literature on MMC-induced HUS in Japan was reviewed, and the relationship between the prognosis and the patients conditions, such as sex, age, site of primary cancer, total dose of MMC, latent period from MMC administration, laboratory findings at the time of diagnosis and treatment with steroids or plasma exchange, were analysed. Patients less than 60 years old or treated with plasma exchange were found to be associated significantly with a favorable outcome. The most frequent cause of death was pulmonary edema or respiratory failure. In conclusion, early treatment with plasma exchange appeared to result in a better prognosis.

Adult↗
PubMed1993

[Inducing ability of co-planar PCBs toward bilirubin UDP-glucuronyltransferase of liver microsomes: the remarkable difference between guinea pigs and rats].

The induction of liver microsomal UDP-glucuronyltransferase (UGT) activity toward bilirubin by pretreatment with 3, 4, 3', 4'-tetrachlorobiphenyl (TCB), 3, 4, 5, 3', 4'-pentachlorobiphenyl (PenCB) and 3-methylcholanthrene (MC) was studied in guinea pigs and rats. In addition, microsomal benzo(a)pyrene 3-hydroxylase and cytosolic DT-diaphorase activities were also measured for the comparison. All of the PenCB, TCB and MC significantly induced the bilirubin UGT activity of guinea pig liver microsomes. The highest induction (6-fold over the control) was seen in the PenCB-treated animal, and MC (3.2-fold) and TCB (2.4-fold) were less effective. On the other hand, the induction of benzo(a)pyrene 3-hydroxylase and DT-diaphorase activities of guinea pigs was not so remarkable as that of bilirubin UGT activity. In the guinea pig, the inducibility of bilirubin UGT activity seemed to be correlated with the toxicity induced with PenCB, TCB and MC. In contrast to the guinea pig, UGT activity toward bilirubin in the rat was significantly decreased by the treatment with the inducers described above. These results suggest that bilirubin UGT activity in the guinea pig can be an index for the toxicity of polychlorinated biphenyls as like as benzo(a)pyrene 3-hydroxylase and DT-diaphorase activities in the rat.

Animals↗
PubMed1993

Gamma/delta T-cell lymphoma with hepatosplenomegaly: report of a case.

We describe the case of a patient with peripheral gamma/delta T-cell lymphoma (T-ML) with hepatosplenomegaly, generalized lymphadenopathy, and bone marrow involvement. A 44-year-old man had lymphoma, which became clinically apparent 2 months after the onset of myositis and insulin-dependent diabetes mellitus. A cervical lymph node biopsy specimen showed diffuse infiltration by large neoplastic cells with vascular proliferation. The neoplastic cells expressed the T-cell receptor (TCR)delta chain detected by TCR delta 1 and delta-TCS1, CD3, CD30, CD45RO, and epithelial membrane antigen, but not the TCR beta chain detected by beta F1, CD1a, CD2, CD4, CD5, CD7, CD8, CD25, HLA-DR, and terminal deoxynucleotidyl transferase. The cells had a clonal rearrangement of TCR gamma chain gene and a germ-line configuration of immunoglobulin heavy chain gene and TCR beta chain gene. Despite chemotherapy, the patient died of refractory lymphoma 4 months after diagnosis. Examination at autopsy revealed that the main hepatic and splenic neoplastic infiltration sites were the portal area and white pulp, respectively. Our patient differed from those with gamma/delta T-ML with hepatosplenic involvement reported previously with respect to the hepatic and splenic neoplastic infiltration patterns and the presence of lymphadenopathy.

Adult↗
PubMed1992

Resistance of the melibiose carrier to inhibition by the phosphotransferase system due to substitutions of amino acid residues in the carrier of Salmonella typhimurium.

The melibiose carrier of Salmonella typhimurium is under the control of the phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS). We isolated mutants of the melibiose carrier that showed resistance to inhibition via the PTS. Growth of the mutants on melibiose was not inhibited by 2-deoxyglucose, a non-metabolizable substrate of the PTS, although growth of the parent strain was inhibited. Transport activity of the melibiose carrier in the mutants was fairly resistant to inhibition by 2-deoxyglucose, although the activity in the parent was sensitive to inhibition. We cloned the mutated melB gene that encodes the melibiose carrier, determined the nucleotide sequences, and identified replaced nucleotides. The mutations resulted in substitutions of Asp-438 with Tyr, Arg-441 with Ser, or Ile-445 with Asn. All of these residues are in the COOH-terminal region of the carrier. The secondary structure of this region is predicted to be an alpha-helix, and the mutated residues were on the same side of the helix. This region showed sequence similarity to a region of the MalK protein, in which substitution of amino acid residues also resulted in PTS-resistant mutants. Thus the COOH-terminal portion of the melibiose carrier is important for the interaction of dephosphorylated IIIGlc, which is an entity causing reversible inactivation of the carrier.

Amino Acid Sequence↗
PubMed1992

Detection of a new mutant alpha-1-antichymotrypsin in patients with occlusive-cerebrovascular disease.

A new mutant alpha-1-antichymotrypsin (variant ACT) was found by direct sequencing and PCR-single strand conformation polymorphism (PCR-SSCP). This variant ACT was a point mutation of exon V of ACT, with the substitution of Met by Val. Four out of six individuals with this variant ACT had occlusive-cerebrovascular disease, leading to one hypothesis that there might be an association between this mutation and occlusive-cerebrovascular disease.

Base Sequence↗
PubMed1992

The primary structure of mouse saposin.

The primary structure of mouse sphingolipid activator protein (saposin) was determined by cDNA sequencing. The amino acid sequence predicted by the cDNA sequence revealed that mouse saposin was highly homologous to human saposin and also to rat sertoli cell glycoprotein. Mouse saposin also has four functional domains, which are structurally similar to each other, and each domain has cysteines, prolines, and a potential glycosylation site at an almost identical position. An amino acid comparison between human and mouse saposins revealed that the similarity was approximately 70%, and human saposin lacks thirty-one amino acids between domains C and D. Heterogeneities of mRNA were found in both the coding and noncoding regions.

Amino Acid Sequence↗
PubMed1992

Synergistic inhibition of human gastric carcinoma cell growth by 1-beta-D-arabinofuranosylcytosine and hydroxyurea or 2'-deoxyguanosine in vitro.

The cytotoxicity of 1-beta-D-arabinofuranosylcytosine (ara-C) in combination with hydroxyurea (HU) or 2'-deoxyguanosine (GdR) on human gastric carcinoma MK-1 cells and colon carcinoma HT-15 cells was studied. Synergistic interaction between ara-C and HU on MK-1 cells and HT-15 cells, or ara-C and GdR on MK-1 cells was shown using the combination index method. HU increased the accumulation of ara-C triphosphate (ara-CTP) in the acid-soluble pool and diminished the cellular deoxyCTP (dCTP) pool. HU had no effect on the incorporation of ara-C into DNA and RNA. These results indicate that HU-induced elevation in ara-CTP and decrease in dCTP are the basis for synergy among ara-C and HU in MK-1 cells. GdR diminished cellular dCTP slightly, but it decreased the accumulation of ara-CTP in the acid-soluble pool and did not increase the incorporation of ara-C into DNA. On the other hand, ara-C increased cellular deoxyGTP (dGTP) level in the presence of GdR. These results indicate that synergy between ara-C and GdR is mediated through increased cellular dGTP which might inhibit DNA synthesis directly.

Carcinoma↗