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Biomedical subjects

T Matsuda

Publications and source records attributed to T Matsuda.

At least 19 recordsLinked to original sources
PubMed1992

Prothrombin Himi: a compound heterozygote for two dysfunctional prothrombin molecules (Met-337-->Thr and Arg-388-->His).

A congenitally dysfunctional form of prothrombin, Prothrombin Himi, shows reduced fibrinogen clotting activity, although it retains full hydrolytic activity toward synthetic substrates. To elucidate the structural abnormality of the variant prothrombin, we first performed genetic analysis of dysprothrombin. Polymerase chain reaction amplification of the exons 8 through 14 of the proband and her family members' prothrombin genes, which code the thrombin moiety, followed by single-strand conformation polymorphism analysis, identified two variant conformers in exon 10 specific to this family. One variant allele detected in the father was inherited by the proband and one of her sisters, and the other detected in the mother was also inherited by them. This result indicates that the proband has two different base pair changes in the gene. Sequencing showed two novel point mutations in the proband's gene. One is a T to C transition at position 8751, resulting in the substitution of threonine for methionine at codon 337 (Thrombin Himi I). The other is a G to A transition at 8904, resulting in the substitution of histidine for arginine at codon 388 (Thrombin Himi II). By sequencing analysis of her parents, it was determined that Thrombin Himi I was inherited from the father and Thrombin Himi II from the mother. These results confirm that Prothrombin Himi is compound heterozygous for two dysfunctional prothrombin molecules.

Amino Acid Sequence↗
PubMed1992

Sex difference for tolerance of 5-HT1A receptor-mediated temperature and corticosterone responses in mice.

Repeated treatment with 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) resulted in significant attenuation of 8-OH-DPAT-induced hypothermia and adrenocorticol effect in mice of both sexes, while it did not affect the 8-OH-DPAT-induced decrease in 5-hydroxyindoleacetic acid in the hypothalamus in either sex. The attenuated responses developed more rapidly in female than in male mice, indicating sex differences in the adaptive regulation of the 5-HT1A receptor-mediated responses.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1992

[Conformation radiotherapy of carcinoma of the prostate].

During the period from 1975 to 1989, 84 patients with carcinoma of the prostate were treated with conformation radiotherapy at Tokyo Metropolitan Komagome Hospital. The radiation field encompassed only the area of the prostate gland; it did not include the pelvic lymph nodes. The clinical stage of the 84 tumors was 22 in Stage A, 31 in Stage B, 15 in Stage C and 16 in Stage D. The average age of patients was 73.4 years, with range of 54 to 88 years. The average dose to the tumor was 65.7 Gy, with range of 60 Gy to 70 Gy. Hormone therapy was applied to 42 cases. The 5- and 10-year cumulative survival rates were 90.7% and 70.5% for Stage A, 41.7% and 26.7% for Stage B, 48.9% and 48.9% for Stage C, and 32.6% and 0% for Stage D, respectively. The 5-year cause-specific cumulative survival rates were 100% for Stage A, 92.3% for Stage B, 65.0% for Stage C and 40.3% for Stage D, respectively. Patients with poorly differentiated adenocarcinomas or undifferentiated carcinomas showed poorer survival than those with well-differentiated carcinoma. Only 7 cases suffered in-field recurrence, and 2 cases suffered recurrence at pelvic lymph nodes. Acute reactions were noted in 13 cases. Late complications following treatment were acceptable. Mild to moderate complications were recognized in 2 cases, but neither patient required surgery. In conclusion, our data suggest the advantage of the conformation technique applied to radiation therapy for carcinoma of the prostate.

Aged↗
PubMed1992

Nucleotide sequence of a cDNA clone encoding a major allergenic protein in rice seeds. Homology of the deduced amino acid sequence with members of alpha-amylase/trypsin inhibitor family.

A cDNA clone of rice major allergenic protein (RAP) was isolated from a cDNA library of maturing rice seeds. The cDNA had an open reading frame (486 nucleotides) which coded a 162 amino acid residue polypeptide comprising a 27-residue signal peptide and a 135-residue mature protein of M(r) 14,764. The deduced amino acid sequence of RAP showed a considerable similarity to barley trypsin inhibitor [1983, J. Biol. Chem. 258, 7998-8003] and wheat alpha-amylase inhibitor [1981, Phytochemistry 20, 1781-1784].

Allergens↗
PubMed1992

Interferon-gamma gene expression in unstimulated bone marrow mononuclear cells predicts a good response to cyclosporine therapy in aplastic anemia.

Cyclosporine (CyA) therapy has been shown to be effective in some patients with aplastic anemia. In an attempt to characterize aplastic patients likely to benefit from CyA therapy, we examined bone marrow mononuclear cells (BMMC) obtained before therapy from 23 patients with aplastic anemia, who were treated with CyA alone. Expression of four myelosuppressive cytokines, including tumor necrosis factor (TNF), lymphotoxin, macrophage inflammatory protein-1 alpha (MIP-1 alpha), and interferon-gamma (IFN-gamma) was examined using polymerase chain reaction (PCR)-assisted messenger RNA (mRNA) amplification. mRNA for TNF, lymphotoxin, and MIP-1 alpha was readily detectable at variable levels in BMMC from normal and transfused controls as well as in BMMC from aplastic patients. In contrast, IFN-gamma mRNA was only demonstrable in BMMC from some patients with aplastic anemia, irrespective of a history of transfusions. Of 13 patients who responded to CyA therapy and achieved transfusion-independence, IFN-gamma mRNA was detected in 12 patients, whereas the mRNA was only detectable in 3 of 10 patients refractory to CyA therapy (P = .003, Fisher's exact test). Follow-up examination of BMMC obtained from seven CyA-responding patients after hematologic remission showed disappearance of IFN-gamma mRNA in four patients. These results suggest that detection of IFN-gamma gene expression in pretreatment BMMC from aplastic patients using PCR may be helpful in predicting a good response to CyA therapy.

Adolescent↗
PubMed1992

Mapping of antigenic sites to monoclonal antibodies on the primary structure of the F1-ATPase beta subunit from Escherichia coli: concealed amino-terminal region of the subunit in the F1.

To analyze relationships between the ternary and primary structures of the beta subunit of Escherichia coli F1 ATPase, we prepared two monoclonal antibodies beta 12 and beta 31 against the beta peptide. These antibodies bind to the beta subunit but do not bind to the F1 ATPase, resulting in no inhibition of the ATPase activities. Several different portions of the beta subunit peptide were prepared by constructing expression plasmids carrying the corresponding DNA segment of the beta subunit gene amplified by the polymerase chain reaction. Western blotting analysis using these peptides revealed that the antibodies bound to a peptide of 104 amino acid residues from the amino terminal end, which is outside the previously estimated catalytic domain between residues 140 and 350. These results indicated that the amino terminal portion of the maximal 104 residues is not exposed to the surface of the F1 ATPase. The binding spectrum of the antibodies to the subunit from various species including Vibrio alginolyticus and thermophilic bacterium PS3 indicated possible epitope sequences within the 104 residues. The ternary structure of the beta subunit, in terms of cleavage sites by endopeptidases, was analyzed using the antibodies. A 43-kDa peptide without binding ability to beta 12 and beta 31 appeared upon cleavage by lysyl endopeptidase. The results suggested that lysyl residues from around 70 to 100 from the amino terminus are exposed to the surface of the beta subunit.

Amino Acid Sequence↗
PubMed1992

[Thermoradiotherapy for adenocarcinoma of the rectum and sigmoid--application to primarily inoperable and recurrent cases].

Between February 1983 and May 1990, 19 rectal cancers and three sigmoid colon cancers were treated with thermoradiotherapy. Among four patients with primary rectal cancer, one received preoperative treatment and three were judged inoperable. All the inoperable patients responded well to treatment and were judged operable. Pathological examination of the resected specimens confirmed the effectiveness of treatment. In one case in particular, no cancer cells were observed in the specimen or at autopsy, 21 months after thermoradiotherapy. Eighteen cases of recurrent colorectal cancer were also treated. Judged by tumor shrinkage alone, these patients were classified into five cases of PR and 13 of NR. When the low density area seen on CT images after treatment was added to the criteria, there was one case of CR, six of PR, and 11 of NR, and the effectiveness ratio shown by the sum of CR and PR was 38.9%. Fourteen cases in the thermoradiotherapy group and 16 in the radiation therapy group were compared as to the reduction in postoperative perineal pain caused by recurrence at the pre-sacral area. It was found that thermoradiotherapy was significantly superior to radiation therapy in the frequency and duration of pain relief. Although most patients complained of the sensation of heat, this was within tolerable limits, and no severe side effects were experienced.

Adenocarcinoma↗
PubMed1992

Glucose and oxygen deprivation induces a Ca(2+)-mediated decrease in (Na(+)+K+)-ATPase activity in rat brain slices.

Exposure of rat brain cortical slices to a medium lacking in glucose, oxygen or both glucose and oxygen, resulted in a decrease of the tissue ATP content and a reduction of (Na(+)+K+)-ATPase activity in membranes prepared from the slices. These treatments also inhibited partial reactions of (Na(+)+K+)-ATPase such as Na(+)-dependent phosphorylation and K(+)-stimulated phosphatase, as well as specific binding of [3H]ouabain in membranes prepared from the slices. Glucose deprivation and hypoxia decreased (Na(+)+K+)-ATPase activity in the absence of extracellular Ca2+, but the effects were blocked by 1,2-bis(2-amino-phenoxy)ethane-N,N,N',N'-tetraacetic acid tetra-acetomethyl ester (BAPTA-AM), a chelator of intracellular Ca2+. Metabolic inhibitors mimicked the effects of glucose deprivation and hypoxia. The effect of glucose-free hypoxia was dependent on extracellular Ca2+. It was blocked by Mg2+ at high concentration, bepridil or amiloride, but not by voltage-sensitive Ca2+ channel antagonists and glutamate receptor antagonists. None of the drugs tested here, except for dithiothreitol, affected the inhibitory effect of glucose-free hypoxia on the enzyme activity. In contrast to brain (Na(+)+K+)-ATPase, the kidney enzyme was insensitive to glucose and oxygen deprivation and metabolic inhibitors which depleted the tissue ATP.

Animals↗
PubMed1992

Postnatal change in a Ca(2+)-mediated decrease in (Na+ + K+)-ATPase activity in rat brain slices.

The treatment of brain slices from immature rats with veratrine and monensin did not cause any change in (Na+ + K+)-adenosine triphosphatase (ATPase) activity or [3H]ouabain binding in membranes prepared from the slices, though these reagents remarkably stimulated Ca2+ uptake in the slices. Exposure of the slices from adult rats to a glucose-free, hypoxic or both glucose-free and hypoxic medium resulted in a decrease in the enzyme activity, but the enzyme from immature rats was resistant to the conditions.

Animals↗
PubMed1992

Determinants of response to the DNA topoisomerase II inhibitors doxorubicin and etoposide in human lung cancer cell lines.

BACKGROUND: Small-cell lung cancer (SCLC) is more sensitive to anticancer agents than non-small-cell lung cancer (NSCLC), but few studies have analyzed the mechanisms of natural drug resistance responsible for this difference. PURPOSE: To elucidate these mechanisms, we determined drug sensitivity and evaluated the biochemical parameters affecting response to the DNA topoisomerase II inhibitors doxorubicin and etoposide in both types of cancer cell lines, in particular the activity and content of DNA topoisomerase II, as well as etoposide uptake and cell doubling time. METHODS: Drug sensitivity and cellular uptake of etoposide were determined by clonogenic assay and accumulation of radiolabeled drug, respectively. The topoisomerase II activity was assayed by decatenation of kinetoplast DNA to minicircle DNA using nuclear protein, and the content was determined by immunoblot analysis of nuclear extracts. We also compared the topoisomerase II content in parent cell lines with that in lines with cisplatin resistance acquired in vitro. RESULTS: Sensitivities to doxorubicin and etoposide were higher in SCLC cell lines than in NSCLC lines, and the difference was statistically significant. Etoposide uptake in SCLC cells was higher than in NSCLC cells; the difference was statistically significant, but this difference may not be sufficient to account for the variation in sensitivities of the cell lines. Topoisomerase II activities of nuclear protein from SCLC cell lines were reproducibly twofold higher than those for NSCLC cell lines. The topoisomerase II content in nuclear protein appeared to be higher in SCLC cell lines than in NSCLC cell lines and corresponded to the sensitivities to doxorubicin and etoposide. In the cisplatin-resistant NSCLC cell lines PC-7/CDDP and PC-14/CDDP, the topoisomerase II content was increased compared with that in the parent lines, but the topoisomerase II content in other cisplatin-sensitive parent lines was similar to that in resistant sublines. CONCLUSIONS: These findings suggest that the topoisomerase II activity and content may be major factors in determining sensitivity to topoisomerase II inhibitors.

Carcinoma, Non-Small-Cell Lung↗
PubMed1992

Generation of plasmacytomas with the chromosomal translocation t(12;15) in interleukin 6 transgenic mice.

The mechanisms through which pristane or mineral oil can induce plasmacytomas in BALB/c or NZB mice are not fully understood, but involvement of interleukin 6 (IL-6), a growth factor for plasmacytomas and myelomas, has been strongly suggested. To clarify the role of IL-6 in plasmacytomagenesis, a human IL-6 cDNA was introduced into mouse germ lines under the transcriptional control of the murine major histocompatibility complex class I (H-2Ld) promoter. IL-6 transgenic mice of C57BL/6 origin developed a massive plasmacytosis but not plasmacytomas. However, introduction of BALB/c genetic background into IL-6 transgenic mice could generate monoclonal transplantable plasmacytomas with the chromosomal translocation t(12;15). These results provide firm evidence of the critical role of IL-6 in the plasmacytoma development.

Animals↗
PubMed1992

Immunogenicity and reactogenicity of Takeda acellular pertussis-component diphtheria-tetanus-pertussis vaccine in 2- and 3-month-old children in Japan.

OBJECTIVE: To compare the reactogenicity and immune response to the Takeda acellular pertussis-component diphtheria-tetanus-pertussis (APDT) vaccine in children when immunization commenced at 2 months (group A) vs 3 months (group B) of age. DESIGN: Longitudinal, nonblinded, comparative study. SETTING: Pediatric well-child clinics. PARTICIPANTS: Healthy 50- to 98-day-old infants. RESULTS: Good antibody responses to lymphocytosis-promoting factor, filamentous hemagglutinin, agglutinogens, and pertactin occurred in both age groups after both the third and fourth vaccine doses. Both young age and transplacentally acquired maternal antibody independently and together have a suppressive effect on the response to the four antigens in this APDT vaccine. However, these effects appear to be minor. Vaccine reactions were mild; group A children had slightly but not significantly higher rates than group B children. CONCLUSION: The present US diphtheria and tetanus toxoids and pertussis vaccine immunization schedule should also be satisfactory with this acellular pertussis component vaccine.

Age Factors↗
PubMed1992

The role of interleukin 6 in plasmacytomagenesis.

Interleukin 6 (IL-6) is a polyfunctional cytokine which regulates the immune response, the acute-phase reaction and haemopoiesis. IL-6 plays a critical role in differentiation of B cells into plasma cells, and is a potent growth factor for plasmacytomas and myelomas. A relationship between IL-6 and polyclonal plasma cell abnormalities has been demonstrated. Abnormal production of IL-6 was first suggested to be related to hypergammaglobulinaemia with autoantibody production in patients with cardiac myxoma. A role of IL-6 in the generation of plasmacytoma has also been indicated. In support of these clinical and experimental observations, we demonstrated that transgenic C57BL/6 mice carrying the human IL-6 gene showed a massive polyclonal plasmacytosis with production of autoantibodies. However, the tumour was not transplantable to syngeneic animals. Susceptibility to pristane-induced plasmacytomagenesis is genetically determined--pristane can induce plasmacytomas in BALB/c but not in C57BL/6 mice. IL-6 transgenic C57BL/6 mice were backcrossed to BALB/c mice to elucidate the genetic influence on plasmacytomagenesis. Transplantable monoclonal plasmacytoma with a t(12;15) chromosomal translocation was generated in some of the backcrossed mice, indicating that IL-6 plays a key role in the multistep oncogenesis of plasma cell neoplasia.

Animals↗
PubMed1992

Increased levels of plasma thrombomodulin in chronic myelogenous leukemia.

Circulating blood plasma contains proteinase-degraded forms of thrombomodulin that are soluble. We quantitatively assayed the plasma levels of thrombomodulin in 15 patients with chronic myelogenous leukemia (CML) in chronic phase by method of an enzyme-linked immunosorbent assay using a monoclonal antibody to protease-degraded products of thrombomodulin. Plasma levels of thrombomodulin in patients with CML at diagnosis were significantly increased (19.5 +/- 6.2 ng/ml: means +/- SD) compared with the levels in normal controls (8.0 +/- 1.9 ng/ml, n = 20) (P less than 0.001). Fibrin degradation products (D-dimer), thrombin-antithrombin III complex, and plasmin alpha 2-antiplasmin complex were almost normal, suggesting that intravascular coagulation or plasmin-mediated fibrinolysis little occurred in these patients. On the other hand, the plasma levels of elastase-alpha 1-proteinase inhibitor (E-alpha 1PI) complex, which was the indicator of released leukocyte elastase, were significantly increased in CML (P less than 0.0001). The plasma levels of thrombomodulin and E-alpha 1PI complex were decreased in parallel with decline of leukocyte counts in 10 patients with CML following anti-leukemic therapy. Furthermore, a statistically significant correlation was observed between the plasma levels of thrombomodulin and E-alpha 1PI complex obtained at 39 time points in 15 patients with CML (r = 0.81, P less than 0.001). These results suggest that the increased plasma levels of thrombomodulin in CML may be partly caused by leukocyte elastase, which may split the surface thrombomodulin and release protease-degraded fragments of it into the circulation.

Antineoplastic Agents↗