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Biomedical subjects

A Matsuda

Publications and source records attributed to A Matsuda.

At least 235 records · Page 13Linked to original sources
PubMed1996

[Gaucher disease type 1, incidentally found on a periodic physical examination].

A 33-year-old man was admitted to our hospital because of thrombocytopenia found on a periodic physical examination. Splenomegaly was recognized Peripheral blood showed WBC 4,510/microliters, Hb 12.5 g/dl, and Plt 40,000/microliters. Increased serum levels of acid phosphatase and angiotensin converting enzyme were observed on laboratory tests. Bone marrow aspirate revealed Gaucher cells. Decreased beta-glucosidase activity was demonstrated in blood leukocytes, cultured blood lymphocytes, and cultured bone marrow fubroblasts from the patient. His glucocerebrosidase genotype was T1448C/C1504T (L444P/R463C). Since neurological examination and skeletal X ray results were normal, Gaucher disease type 1 was diagnosed.

Adult↗
PubMed1996

The prevalence of low insulin responders to oral glucose load among groups with various patterns of family history of diabetes.

The prevalence of low insulin responders was assessed in non-diabetic subjects with various patterns of family history of diabetes. Subjects were divided into five groups: group A, without any family history of diabetes among all known relatives; group B, with diabetes among parents and/or siblings; group C, with one diabetic parent; group D, with two diabetic parents; and group E, non-diabetic co-twins of monozygotic twins with diabetes. Except twins, the type of diabetes in the family was not defined. They were examined by 100 g oral glucose tolerance test (OGTT) except for group E in which 50 g or 75 g OGTT were also used. Insulin response was evaluated by the insulinogenic index, the ratio of increment of serum insulin to that of plasma glucose (mg dl-1) 30 min after the oral glucose load. The low insulin responders had a lower insulinogenic index below 0.5 in the case of 100 g OGTT, and below 0.35 and 0.4 in the case of 50 g and 75 g OGTT. Groups with a family history of diabetes (B, C, and D) had significantly lower insulinogenic indices than group A without a family history of diabetes. The prevalence of low insulin responders was significantly higher in subjects with a strong family history of non-insulin-dependent diabetes mellitus (NIDDM), such as subjects with two diabetic parents and monozygotic co-twins of NIDDM patients. In group A, low insulin responders were more prevalent in older subjects, while in group D, they were also frequent in younger subjects. These results suggest that a low insulin response has a genetic basis and is a preclinical feature in subjects with genetic pre-disposition to NIDDM.

Adolescent↗
PubMed1996

[Epidural administration of buprenorphine after combined spinal epidural anesthesia].

We compared the efficacy of epidurally administered buprenorphine (0.2 mg) after combined spinal-epidural anesthesia (CSE group) and that after general anesthesia combined with epidural anesthesia (EPI + GEN group). Postoperatively epidural buprenorphine was administered for initial pain relief significantly later in CSE group than in EPI + GEN group. The duration of pain relief with epidural buprenorphine was similar in both groups (about 11 hours). The time period until postoperative first walk and the number of pain relief medication were also similar in both groups. We had the impression that the onset of pain relief was faster in CSE group, probably because there might be flux of buprenorphine through a dural hole just after epidural administration.

Analgesia, Epidural↗
PubMed1995

The synthesis of blocked triplet-phosphoramidites and their use in mutagenesis.

A general approach for the synthesis of oligonucleotide-triplet phosphoramidites and the synthesis of four such blocks are described. A strategy was devised to minimize the number of dimer precursors needed for synthesis of a complete set of triplet-amidite blocks encoding all 20 amino acids. Whereas synthesis of 20 triplet-amidite blocks consisting of codon sequences requires 16 dimer blocks, just seven dimer blocks are required to synthesize all required antisense sequences. The antisense sequences are then converted to codons in template mediated replication. Using a mixture of four triplet-amidites and conventional automated solid-phase DNA synthesis, short (6mer) and medium length (30mer) oligonucleotide mixtures were synthesized and analyzed. The latter was replicated in vitro and used as a mutagenic cassette to produce four mutants of Asp 221 in the enzyme thymidylate synthase. The method establishes the direction and utility for the production and use of triplet-amidite blocks in DNA synthesis.

Amides↗
PubMed1995

Nucleosides and nucleotides. 141. Chemical stability of a new antitumor nucleoside, 2'-C-cyano-2'-deoxy-1-beta-D-arabino-pentofuranosylcytosine in alkaline medium: formation of 2'-C-cyano-2'-deoxy-1-beta-D-ribo-pentofuranosylcytosine and its antitumor activity.

We have designed 2'-C-cyano-2'-deoxy-1-beta-D-arabino- pentofuranosylcytosine (CNDAC) as a potential mechanism-based DNA-strand-breaking nucleoside, which showed potent tumor cell growth inhibitory activity against various human tumor cell lines in vitro and in vivo. When measuring the pKa of the 2' alpha-proton of CNDAC, we found that CNDAC epimerized to 2'-C-cyano-2'-deoxy-1-beta-D-ribo-pentofuranosylcytosine (CNDC) with concomitant degradation of both CNDAC and CNDC to cytosine and 1,4-anhydro-2-C-cyano-2-deoxy-D-erythro-pent-1- enitol. Kinetic analysis of these reactions showed that abstraction of the acidic 2'-proton of CNDAC and CNDC initiated the reactions, which quickly reached an equilibrium. In the equilibrium, a concentration ratio of CNDAC and CNDC was about 3:5. Concomitant degradation of these nucleosides was found to be rather slow. Deuterium incorporation experiments with CNDAC in a D2O buffer suggested the mechanism of the beta-elimination reactions is an E1cB type. These epimerization and degradation reactions were found even in neutral conditions (pH 7.5) and also occurred in RPMI 1640 cell culture medium. The discovery of which nucleoside possesses the predominate tumor cell growth inhibitory activity was important. While both nucleosides showed potent tumor cell growth inhibitory activity against three human tumor cell lines (colon carcinoma WiDr, small cell lung carcinoma SBC-5, and stomach carcinoma MKN-74 cells) in 48 h of incubation, in 20 min of incubation, CNDAC was 11-50 times more effective than CNDC. In vivo antileukemic activity of these nucleosides against a mouse P388 model, CNDAC was obviously superior to CNDC.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1995

(+/-)-(Z)-2-(aminomethyl)-1-phenylcyclopropanecarboxamide derivatives as a new prototype of NMDA receptor antagonists.

(+/-)-(Z)-2-(Aminomethyl)-1-phenylcyclopropane-N,N-diethylcarbo xamide (milnacipran, 1), a clinically useful antidepressant, and its derivatives were prepared by an improved method and were evaluated as NMDA receptor antagonists. Of these, milnacipran (1), its N-methyl and N,N-dimethyl derivatives, 7 and 8, respectively, and its homologue 12 at the aminomethyl moiety had binding affinity for the receptor in vitro (IC50: 1, 6.3 +/- 0.3 microM; 7, 13 +/- 2.1 microM; 8, 88 +/- 1.4 microM; 12, 10 +/- 1.2 microM). These also protected mice from NMDA-induced lethality. These compounds would be important as anovel prototype for designing potent NMDA-receptor antagonists because of their characteristic structure, which clearly differentiated them from known competitive and noncompetitive antagonists to the receptor.

Animals↗
PubMed1995

Elevated ratio of summed serum proinsulin to insulin response after oral glucose load in type 2 diabetes decreases following sulfonylurea treatment.

We showed previously that the disproportionate elevation of serum proinsulin at fasting and after glucose ingestion in Type 2 diabetes is reduced to nearly normal after improvement of glycemic control by diet therapy. In this study, we investigated the effect of sulfonylurea (SU) treatment on serum proinsulin levels and proinsulin/insulin ratio (PI/I) during oral glucose tolerance test in patients with Type 2 diabetes. Thirteen diabetic patients (age 56 +/- 9 years, body mass index 22.4 +/- 1.9 kg/m2, mean +/- SD) were examined by 75 g oral glucose tolerance test (OGTT) before and after glycemic control by SU therapy. Mean interval of two OGTTs was 126 days. Serum proinsulin was measured by the radioimmunoassay using a human proinsulin-specific antiserum. When glycemic control improved after SU therapy (mean fasting plasma glucose 11.5 and 6.0 mmol/l, before and after SU treatment), fasting insulin, proinsulin and PI/I ratio did not change significantly. Insulin response during OGTT markedly increased after SU therapy. Summed value of insulin (sigma I) increased from 634 to 1064 pmol/l after SU (P < 0.01), whereas summed proinsulin (sigma PI) did not change significantly (146 and 159 pmol/l), resulting in a significant decrease in sigma PI/sigma I (23.6-15.1%, P < 0.05). We conclude that the disproportionate elevation of proinsulin during OGTT in patients with Type 2 diabetes can be reduced after glycemic control by SU treatment, chiefly by a selective increase in insulin response.

Administration, Oral↗
PubMed1995

Nucleosides and nucleotides--CXXXVII. Antitumor phospholipids with 5-fluorouridine as a cytotoxic polar-head: synthesis of 5'-phosphatidyl-5-fluorouridines by phospholipase D-catalyzed transphosphatidylation.

5'-Phosphatidyl-5-fluorouridines, with the same backbone structure as that of natural phospholipids, in which a polar-head group of usual phospholipids is replaced by 5-fluorouridine, were designed to be potent antitumor agents. 5'-Phosphatidyl-5-fluorouridines with a variety of diacyl or dialkyl residues in the glycerol moiety, were synthesized by phospholipase D-catalyzed transphosphatidylation from the corresponding phosphatidylcholine and 5-fluorouridine. These new compounds were evaluated in mice with experimental tumors by ip and po administration. Dipalmitoyl and distearoyl derivatives 1b and 1c had the greatest antitumor activity against both P388 leukemia and Meth A fibrosarcoma in mice.

Animals↗
PubMed1995

Graves' hyperthyroidism following transient thyrotoxicosis during interferon therapy for chronic hepatitis type C.

We report a case of Graves' hyperthyroidism induced by long-term interferon (IFN) therapy. A 52-year-old woman suffered from chronic active hepatitis type C and was treated with a total of 456 x 10(6) units of IFN-alpha for 23 weeks. During the 12th week of treatment she showed transient thyrotoxicosis. One week after the termination of IFN therapy, TSH-receptor antibodies became positive and subsequently she showed Graves' hyperthyroidism. This case showed sequential manifestation from transient thyrotoxicosis to the appearance of TSH-receptor autoantibodies, and then the occurrence of Graves' hyperthyroidism during IFN therapy. The course of this case may be useful in the understanding of the pathogenesis of autoimmune hyperthyroidism.

Autoantibodies↗
PubMed1995

[Two cases of inferior branch palsy of the oculomotor nerve in children].

Two cases of inferior branch palsy of the oculomoter nerve in children are reported. A Six-year-old and a 14-year-old child had diplopia. Adduction and depression were restricted and mydriasis of the affected eye were observed. There were no restrictions on elevation. Ptosis was absent. They were diagnosed as having inferior branch palsy of the oculomotor nerve. Neurological examinations and diagnostic imagings showed no other abnormalities. Herpes simplex and influenza antibody titer were high in both cases. Oral steroid treatment was given. The eye position and movement recovered within 3 months in both cases. But the light reflexes of the affected eye remained diminished and light-near dissociation were observed. These findings have not changed for two years.

Adolescent↗
PubMed1995

[Acute myeloid leukemia (M1) following chemotherapy for Ki-1 lymphoma complicated with rheumatoid arthritis].

A 58-year-old woman complicated with rheumatoid arthritis (RA) was admitted to our hospital with right axillar lymphadenopathy and splenomegaly in November 1992. She was diagnosed as an anaplastic large-cell lymphoma (Ki-1 +) (stage IIIB) on the histological findings of the right axillar lymph nodes. She was treated with 11 courses of CHOP regimen between February 1992 and May 1993, and with mitoxantrone, etoposide (VP-16) and predonisolone in April 1992 and May 1993. The right axillar lymph nodes and spleen were irradiated at a dose of 36Gy in October 1992 and May 1993 respectively. In May 1993, peripheral blood showed WBC 89,000/microliter with 96% myeloblasts, Hb 8.3 g/dl, and Plt 124,000/microliter. Bone marrow aspirate revealed hypercellularity with 90% myeloblasts, which were positive for CD13 and HLA-DR. She was diagnosed as AML (M1). The karyotype showed normal. Southern blot analysis did not reveal the rearrangement of the MLL gene. She received the BHAC-DMP regimen and obtained complete remission. However, she relapsed during consolidation therapy, and died of cerebral bleeding. An autopsy revealed absence of a residual tumor. The mean interval from exposure to alkylating agent to the onset of secondary leukemia has been reported to be about 5 years, in contrast to a shortened interval of about 2 years for VP-16-induced leukemia. In our patient, it took only 1 year to have AML following chemotherapy for Ki-1 lymphoma. This suggests that her AML might be induced not only by treatments for RA and Ki-1 lymphoma, but also by immunological background such as RA.

Antineoplastic Combined Chemotherapy Protocols↗