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Biomedical subjects

A Matsuda

Publications and source records attributed to A Matsuda.

At least 415 records · Page 23Linked to original sources
PubMed1986

Inhibition of replication and cytopathic effect of human T cell lymphotropic virus type III/lymphadenopathy-associated virus by 3'-azido-3'-deoxythymidine in vitro.

Human T cell lymphotropic virus type III (HTLV-III)/lymphadenopathy-associated virus is the etiologic agent of the acquired immune deficiency syndrome (AIDS) and AIDS-related complex. The effect of 3'-azido-3'-deoxythymidine (AZT) on the HTLV-III/lymphadenopathy-associated virus infection was quantitatively studied with HTLV type I-carrying MT-4 cells. The AZT compound inhibited HTLV-III-induced cytopathic effect and virus-specific antigen expression in MT-4 cells at concentrations of 5 and 10 microM. In addition, a plaque-forming assay was performed to assess the effect of AZT on virus replication in MT-4 cells freshly infected with HTLV-III and in continuous HTLV-III-producing Molt-4/HTLV-III cells. Results showed that AZT efficiently and effectively inhibited the replication of HTLV-III in infected MT-4 cells. AZT is a strong inhibitor of reverse transcriptase activity of HTLV-III as a triphosphate, to such a degree that even 1.0 pM azido-TTP inhibits 50% of reverse transcriptase activity. However, it did not show any effect in the HTLV-III-producing cell line Molt-4/HTLV-III. Thus, AZT has no effect on virus replication of an already integrated virus. When 5 microM AZT was added to HTLV-III-infected MT-4 within 20 h after infection, a striking suppressive effect was noticed. This concentration was much lower than that which inhibits the growth of MT-4 cells. These results confirm those found in a previous report (H. Mitsuya, K. J. Weinhold, P. S. Furman, H. S. Clair, S. N. Lehrman, R. C. Gallo, D. Bolognesi, D. W. Barry, and S. Broder, Proc. Natl. Acad. Sci. USA 82:7096-7100, 1985) and suggest that AZT might be used as an experimental antiviral agent for AIDS and AIDS-related complex.

Antigens, Viral↗
PubMed1986

A new case of abnormal insulinemia with diabetes. Reduced insulin values determined by radioreceptor assay.

A 44-yr-old Japanese woman was found to have diabetes with marked fasting hyperinsulinemia. Her fasting plasma glucose, serum insulin, and C-peptide levels were 137 mg/dl, 204 microU/ml, and 1.13 pmol/ml, respectively, and the C-peptide-to-insulin molar ratio was markedly reduced. Insulin antibodies and insulin-receptor antibodies were negative. Fasting levels of counter-insulin hormones were normal. She had normal hypoglycemic response to exogenous insulin injection. Binding of 125I-labeled insulin to erythrocytes was normal. Oral glucose-tolerance tests in eight members of her first-degree relatives revealed four members (mother, sister, brother, and daughter) with fasting hyperinsulinemia (111-314 microU/ml), and two of them (mother and sister) were overtly diabetic. Thus, the abnormality was thought to be an autosomal dominant trait. Reverse-phase high-performance liquid chromatograph analysis of immunopurified insulin obtained from her serum revealed two peaks of insulin immunoreactivity. The amount of the abnormal insulin peak was seven times greater than that of normal insulin. The abnormal insulin was eluted after bovine, human, and porcine insulins, indicating it has a more hydrophobic nature than normal human insulin. Radioreceptor assay (RRA) for serum insulin with guinea pig kidney membrane revealed that the binding activity of their serum insulin was markedly decreased. Discrepancies between the values measured by RRA and those measured by radioimmunoassay were also found in her family members with hyperinsulinemia but not in her family members without hyperinsulinemia and other hyperinsulinemic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Enhancement of graft-versus-host reaction and delayed cutaneous hypersensitivity in mice by ubenimex.

The effect of ubenimex on graft-versus-host reaction and delayed cutaneous hypersensitivity in mice was studied. Ubenimex enhanced the graft-versus-host reaction in a dose range from 0.005 to 0.5 mg/kg. Ubenimex inhibited the aging-caused decrease of delayed cutaneous hypersensitivity to oxazolone and the efficacy was greater with older mice. Ubenimex also inhibited mitomycin C and L1210-caused decreases of delayed cutaneous hypersensitivity to picryl chloride. However, the excess decrease caused by mitomycin C was not significantly altered by ubenimex.

Adjuvants, Immunologic↗
PubMed1986

Malignant clonal expansion of large granular lymphocytes with a Leu-11+, Leu-7- surface phenotype: in vitro responsiveness of malignant cells to recombinant human interleukin 2.

A 14-year-old Japanese female with neutropenia showed malignant proliferation of the large granular lymphocytes (LGLs). These LGLs were E rosette+ and Fc(IgG) receptor+ and therefore are referred to as T gamma lymphocytes. They were also Leu-11+ and OKT11+; however, they were clearly negative for Leu-7, OKT3, OKT8, OKM1, and HNK-1 antigens as well as for terminal deoxynucleotidyl transferase activity. Karyotype analysis revealed 47, XXX. The LGLs showed no rearrangement of T cell receptor C beta genes. The natural killer (NK) cell activity against K562 target cells was low, but was significantly augmented after stimulation by recombinant human interleukin 2 (IL 2) in contrast to minimal NK boosting by recombinant human gamma-interferon (gamma-IFN). Such a unique responsive ability to lymphokines was quite similar to that noted in fetal and cord blood cells. These LGLs also demonstrated a considerable increase in antibody-dependent cell-mediated cytotoxicity (ADCC) and lymphokine-activated killer (LAK) activity after a short incubation with IL 2. Although in a resting stage they showed no IL 2 receptor expression as examined by anti-Tac antibody, Tac antigen appeared after IL 2 treatment followed by a marked increase in 3H-thymidine incorporation and a remarkable production of gamma-IFN. To investigate the mechanism of neutropenia, in vitro IL 2-stimulated coculture studies of these cells with normal bone marrow cells were performed. Colony formation of myeloid progenitors (CFU-C) was significantly suppressed. In addition, the conditioned medium from IL 2-stimulated LGLs indicated a remarkable suppression of CFU-C. These results suggest that these LGLs with a Leu-11+, Leu-7- surface phenotype might belong to a unique subset of pre-NK cells that are functionally and phenotypically similar to those represented at any early stage of human ontogeny and that they strongly express Tac antigen under the influence of IL 2 administration, followed by remarkable cell proliferation and gamma-IFN production.

Adolescent↗
PubMed1986

Synthesis of a mutagenic nucleoside, 2'-deoxy-2-(p-nitrophenyl)-adenosine.

The reaction of 2-amino-6-chloropurine riboside with i-amyl nitrite in benzene in the presence of Cu2O, followed by treatment with NH3/MeOH gave 2-phenyladenosine (1). The crude sample of 1 was found to be mutagenic to bacteria (Salmonella typhimurium TA 98 and TA 100, without metabolic activation). When this material was subjected to high pressure liquid chromatography, the mutagenic activity was found only in contaminating minor components, whose structures were assigned as 2-(m- and p-nitrophenyl)-adenosines (2m,p). In order to study structure-activity relationships, several nucleoside and base analogues were synthesized. Among them, 2'-deoxy-2-(p-nitrophenyl)-adenosine (8) was the most potent mutagen as tested either with TA 98 or TA 100.

Adenosine↗
PubMed1986

Anti-parasite activity of nucleoside analogues: the metabolism of carbocyclic inosine in promastigotes of Leishmania tropica and Leishmania donovani and its activity against amastigotes of Leishmania donovani in vitro.

Carbocyclic inosine is a potent inhibitor for the growth of the promastigote form of Leishmania tropica and Leishmania donovani. In culture, the EC50 values of carbocyclic inosine are 8.3 X 10(-8) and 1.3 X 10(-7) M for the promastigotes of L. tropica and L. donovani, respectively. On the other hand, it is less toxic towards mouse mammary tumor FM3A cells: the EC50 value is 2.7 X 10(-4)M. Carbocyclic inosine is metabolized by Leishmania promastigotes to give carbocyclic adenosine-5'-triphosphate(aristeromycin-5'-triphosphate) and carbocyclic guanosine-5'-triphosphate. This metabolic conversion provides a mechanism for the parasite-selective toxicity of carbocyclic inosine. Carbocyclic inosine was found to be active against L. donovani amastigotes in an in vivo-like cultivation in vitro.

Animals↗
PubMed1986

Synthesis of 2'-deoxy-6,3'-methano-cyclo-pyrimidine nucleosides.

The nucleophilic attack of lithiated pyrimidines to a suitably-protected 3-ketosugar, afforded the 3-branched sugar stereospecifically, followed by intramolecular glycosylation to give 6,3'-methano-cyclo-pyrimidine nucleosides. The 2'-deoxygenation was achieved by sequential protection, deprotection and radical reduction.

Indicators and Reagents↗
PubMed1985

A comparison of serum C-peptide response to intravenous glucagon, and urine C-peptide, as indexes of insulin dependence.

Serum C-peptide (SCPR) at fasting and after intravenous injection of glucagon was evaluated in diabetic patients with various degrees of insulin dependence, and compared with 24 h urine C-peptide (UCPR). Fasting SCPR did not differ between healthy subjects and sulfonylurea-treated patients (SU) who were considered to have definite non-insulin-dependent diabetes (NIDDM); but was significantly lower in patients with insulin-dependent diabetes (IDDM) (0.24 +/- 0.10 ng/ml in IDDM vs. 1.43 +/- 0.61 ng/ml in SU, P less than 0.001). SCPR reached a peak at 6 min after glucagon injection, except for the IDDM group. The SCPR response at 6 min after 1 mg glucagon injection was significantly lower in the SU (NIDDM) group than in the normal group (2.86 +/- 1.21 v. 4.69 +/- 1.47 ng/ml, P less than 0.001). In the IDDM group, there was no increase of SCPR after glucagon injection. Among diabetic patients, SCPR response to glucagon correlated positively to the amounts of UCPR (P less than 0.001). By analysis of the distribution patterns of SCPR response to intravenous glucagon, SCPR of 1.0 ng/ml and the increment of SCPR of 0.5 ng/ml at 6 min are to be used as cut-off points to differentiate IDDM and NIDDM. These values correspond roughly to the UCPR values below 20 micrograms/day and above 30 micrograms/day, which we previously proposed as indexes to differentiate insulin-dependent and non-insulin-dependent diabetes.

C-Peptide↗
PubMed1985

Urine C-peptide in relation to the degree of insulin dependence in diabetic patients.

Urine C-peptide per 24 h urine (UCPR) was assayed and correlated with the degree of insulin dependence in 324 diabetic patients. The UCPR and UCPR/weight were 74.7 +/- 26.3 micrograms/day and 1.27 +/- 0.36 micrograms/day, kg in healthy subjects, and these values were similar in diet- and sulfonylurea-treated patients. Insulin-dependent diabetics (IDDM) with history of ketosis or ketoacidosis and/or unstable plasma glucose, and patients refractory to sulfonylureas had lower UCPR values (8.5 +/- 6.6 and 22.3 +/- 14.6 micrograms/day) than the other insulin-treated patients (45.4 +/- 30.7 micrograms/day). In more than 90% of diet- and sulfonylurea-treated patients, UCPR exceeded 30 micrograms/day and UCPR/wt. exceeded 0.6 micrograms/day, kg. UCPR was less than 20 micrograms/day and UCPR/wt. less than 0.4 microgram/day,kg in more than 90% of IDDM patients, and less than 40 micrograms/day and 0.8 microgram/day,kg respectively in 80% of sulfonylurea-refractory patients. IDDM patients with more than 20 U/day of insulin doses had lower UCPR values. Longer duration of diabetes was associated with lower UCPR in IDDM patients. The results indicate that UCPR more than 30 micrograms/day or UCPR/wt. more than 0.6 micrograms/day,kg suggest non-insulin dependence, and UCPR less than 20 micrograms/day or UCPR/wt. less than 0.4 micrograms/day,kg suggest insulin dependence. Assay of UCPR provides a simple, non-invasive test for evaluating the degree of insulin dependence in diabetic patients.

Adolescent↗
PubMed1985

Molecular cloning and structure of the gene for 7 beta-(4-carboxybutanamido)cephalosporanic acid acylase from a Pseudomonas strain.

A Pseudomonas strain produced an enzyme capable of deacylating 7 beta-(4-carboxybutanamido)cephalosporanic acid to 7-aminocephalosporanic acid in response to glutaric acid. The gene for the enzyme was cloned within the PstI site of pBR325 as a 7.35-kilobase-pair DNA segment from a mutant of this strain whose enzyme is produced constitutively. The gene expression in the primary clone appeared to be low in Escherichia coli but was significantly enhanced by reducing the size of the initial segment coupled with E. coli promoters. Subsequent subcloning resulted in localization of the gene to a 2.45-kilobase-pair fragment. Three clone-specific polypeptides with molecular weights of ca. 16,000, 54,000, and 70,000 were shown by maxicell analysis. The former two corresponded to the small and large subunits of the purified enzyme from the Pseudomonas strain, and the third polypeptide was suggested to be their precursor. This was supported by DNA sequence study together with amino acid sequencing of the amino terminus of both subunits: the sequences for the small and large subunits were localized contiguously in this order on the structural gene without termination codons between them. The nucleotide sequence also disclosed the presence of a signallike sequence preceding that for the small subunit, consistent with the previous observation that the enzyme might be periplasmic in the Pseudomonas strain. Those results suggest a process for the formation of an active enzyme complex from a precursor through two steps of processing.

Amidohydrolases↗
PubMed1985

Imino acid and related alicyclic amine levels in biological fluids.

Imino acid and related alicyclic amine concentrations in blood and urine of mammals including humans were concurrently determined by a selected ion monitoring technique. Nanomole levels of proline and pipecolic acid, and pyrrolidine and piperidine as well, were found in human urine. Proline levels but not pipecolic acid levels were higher in blood of humans than in urine. Pyrrolidine and piperidine levels in blood of humans were picomole levels and much lower than those in urine. Similar tendencies were also recognized when these 4 compounds were analyzed using animal blood and urine, although the levels were generally higher in animals than in humans. Significantly high concentrations of the imino acids and the amines were found also in animal semen.

Amines↗
PubMed1985

Lipid peroxidation by bleomycin-iron complexes in vitro.

Lipid peroxidation catalyzed by bleomycin (BLM)-metal complexes was studied in vitro using arachidonic acid as the substrate. Iron complexes of BLM caused extensive lipid peroxidation, but other metal complexes did not. The lipid peroxidation caused by the iron complexes was inhibited by antioxidants such as dl-alpha-tocopherol, ascorbic acid etc., but not by other scavengers of hydroxyl and superoxide radicals, and of singlet oxygen. Cyanide ion suppressed the lipid peroxidation caused by BLM-Fe(II), but did not suppress the peroxidation activity of BLM-Fe(III). The peroxidation activity of BLM-Fe(II) was lost instantly by pre-incubation of the complex at 37 degrees C before mixing with arachidonic acid, but that of BLM-Fe(III) was not. These results indicate that the active form for the lipid peroxidation derived from BLM-Fe(II) differs from that of BLM-Fe(III).

Antioxidants↗
PubMed1985

Enhancement of antitumor effect of cytotoxic agents by bestatin.

Bestatin enhanced the antitumor effects of mitomycin C, 5-fluorouracil and cis-dichlorodiammineplatinum against a syngeneic solid tumor of colon adenocarcinoma 26 in BALB/c mice. The enhancement was dependent on administration schedule. Bestatin administration after treatment with the cytotoxic agents was more effective than that made before the treatment.

Adenocarcinoma↗
PubMed1985

Immunological involvement in pulmonary fibrosis induced by peplomycin.

Pulmonary fibrosis in mice induced by peplomycin (PEP) was suppressed by administration of anti-inflammatory agents such as prednisolone and D-penicillamine during or after the administration of PEP. Pulmonary fibrosis was also suppressed by administration of cyclophosphamide, an immunosuppressive antitumor agent before, during or after the administration of PEP. The pulmonary fibrosis in athymic nude mice induced by PEP was less than that in normal mice. The low response in the nude mice was enhanced by transfer of thymocytes to the same level as that in the normal mice. This suggests that the immune system, especially thymus-dependent immunity, is involved in the pulmonary fibrosis induced by PEP.

Animals↗
PubMed1985

[Experimental studies on combination chemotherapy of cisplatin with peplomycin against human squamous cell carcinomas in nude mice].

Combination chemotherapy of cisplatin (CDDP) with bleomycin (BLM) or peplomycin (PEP) has exhibited clinical efficacy against squamous cell carcinomas. The combination of CDDP with PEP was studied using five human squamous cell carcinomas in nude mice. When CDDP was administered before PEP treatment, the combination effect was more pronounced than when CDDP was administered after PEP treatment. Especially, when CDDP was administered 5 or 3 days before PEP treatment, marked delay in growth was shown in 4 out of the 5 human carcinomas. From these results, it is thought that human heterotransplanted tumors in nude mice may provide important information in studies of combination chemotherapy.

Animals↗
PubMed1985

Synthesis and pharmacological activities of 2-alkynyl- and 2-alkenyladenine nucleosides.

A variety of 2-alkynyladenosines (2a-1) were evaluated for biological activity in antiallergic and cardiovascular tests. Compounds bearing 2-C identical to CCH(R)OH side-chain structure exhibited the most potent antiallergic activity at 0.4 mg/kg iv, in rat. These compounds, however, possessed hypotensive activity accompanied by a decrease in heart rate. Compounds substituted at the 2-position by n-pentynyl, n-hexynyl and n-octynyl showed potent hypotensive effect without showing antiallergic activity and a decrease in heart rate. Synthesis and pharmacological activities of 2-alkenyl-adenosines and 2-alkynyl-2'-deoxy- or 3'-deoxyadenosines were also described.

Adenosine↗