Biomedical subjects

A Matsuda

Publications and source records attributed to A Matsuda.

At least 19 recordsLinked to original sources

PubMed1992

Effects of FR 113680 and FK 224, novel tachykinin receptor antagonists, on cigarette smoke-induced rat tracheal plasma extravasation.

We examined the effects of novel tachykinin antagonists, FR 113680 (N alpha-[N alpha-(N alpha-acetyl-L-threonyl)-N1-formyl-D-tryptophyl]-N- methyl-N-phenylmethyl-L-phenylalaninamide) and FK 224 (N-[N2-[N-[N-[N-[2,3-didehydro-N-methyl-N-[N[3-(2-phenthylpheny l) - propionyl]-L-threonyl]-tyrosyl]-L-leucynyl]-D-phenylalanyl]-L-allo - threonyl]-L-asparaginyl]-L-serine nu-lactone) on rat tracheal plasma extravasation induced by cigarette smoke. Intravenous injection of FK 224 (0.032-3.2 mg kg-1) inhibited rat tracheal plasma extravasation induced by cigarette smoke and capsaicin. FR 113680 (32 mg kg-1 i.v.) also significantly inhibited cigarette smoke-induced plasma extravasation, whereas D-chlorpheniramine maleate, FPL 55712, atropine sulfate and indomethacin had no effect. Tracheal plasma extravasation induced by substance P (SP) and neurokinin A (NKA), but not histamine, was also reduced by intravenous administration of FR 113680 and FK 224. These findings suggest that cigarette smoke stimulates primary afferent sensory nerves, releases tachykinins and evokes plasma extravasation in rat trachea.

Amino Acid Sequence↗

PubMed1992

[X-ray examination of the gastrointestinal tract in systemic cutaneous disease].

An X-ray examination of the gastrointestinal tract was performed on 56 patients with systemic cutaneous disease that is often considered associated with internal malignancies. Found were one case of esophageal cancer, two cases of gastric cancer, and two cases of colon cancer. The prevalence of gastric and colon cancer in these patients showed a statistically significant increase compared to the general population. The rate of gastric cancer was 16.26 times higher than the general population and that of colon cancer 32.26. X-ray examination of the gastrointestinal tract in patients with systemic cutaneous disease is useful for detecting malignancy.

Aged↗

PubMed1992

Nucleosides and nucleotides. 112. 2-(1-Hexyn-1-yl)adenosine-5'-uronamides: a new entry of selective A2 adenosine receptor agonists with potent antihypertensive activity.

Chemical modifications of the potent A2 adenosine receptor agonist 2-(1-hexyn-1-yl)adenosine (7, 2-HA) at the 5'-position have been carried out to find more potent and selective A2 agonists. These analogues were evaluated for adenosine A1 and A2 receptor binding affinity in rat brain tissues and antihypertensive effects in spontaneously hypertensive rats (SHR). Among the series of compounds, 2-(1-hexyn-1-yl)adenosine-5'-N-cyclopropyluronamide (16d) had the most potent affinity to the A2 receptor with a Ki of 2.6 nM, which is essentially the same as that of the parent agonist, 2-HA. However, the most selective agonist for the A2 receptor was 2-(1-hexyn-1-yl)adenosine-5'-N-methyluronamide (16b) with a Ki of 11 nM and a 162-fold selectivity. The N-alkyl substituents of 5'-uronamide derivatives did not seem to potentiate the A2 binding affinity but drastically reduced the A1 affinity compared with the parent 2-HA. Therefore, the A1/A2 selectivity was consequently increased. Other 5'-deoxy-5'-substituted derivatives of 2-HA such as the chloro (20), carboxamide (27, 28), sulfonamide (29), urea (30), and thiourea (22) analogues were also prepared. Among these nucleosides, no active compounds with potent or selective affinities to both receptors were found except 20. Although glycosyl conformations and sugar-puckering of these nucleosides were studied by 1H NMR spectroscopy, there were no positive correlations between active and inactive agonists. 2-(1-Hexyn-1-yl)adenosine-5'-uronamide (16a) and 16d had a potent hypotensive effect at ED30 values of 0.18 and 0.17 micrograms/kg, respectively, upon iv administration to anesthetized SHR.

Adenosine↗

PubMed1992

Cloning and disruption of the cefG gene encoding acetyl coenzyme A: deacetylcephalosporin C o-acetyltransferase from Acremonium chrysogenum.

Acetyl CoA: deacetylcephalosporin C o-acetyltransferase(DCPC-ATF) catalyses the final step in the biosynthesis of cephalosporin C (CPC) in Acremonium chrysogenum. The gene encoding DCPC-ATF, cefG, has been isolated from an A. chrysogenum genomic library using a DCPC-ATF cDNA probe. Nucleotide sequence analysis revealed that cefG contains two short introns of 79bp and 65bp. The gene was found to be closely linked to the cefEF gene encoding deacetoxycephalosporin C synthetase/deacetylcephalosporin C synthetase, which catalyses the preceding two steps in the pathway. The two genes are separated by a 1114 bp segment from which they are divergently transcribed. Introduction of the cloned cefG gene to A.chrysogenum resulted in an increased level of DCPC-ATF activity. A plasmid carrying a cefG gene interrupted in the coding region by a selectable marker for resistance to hygromycin B was constructed and used to disrupt the cefG locus in A.chrysogenum. The cefG-disrupted strains were found to lack the ability to produce CPC, and accumulated its precursor, deacetylcephalosporin C in the culture broth. Southern hybridization analysis confirmed that the disruption resulted from a gene replacement event at the cefG locus.

Acetyltransferases↗

PubMed1992

Nucleosides and nucleotides. 107. 2-(cycloalkylalkynyl)adenosines: adenosine A2 receptor agonists with potent antihypertensive effects.

Adenosine receptor-binding profiles in rat brain tissues and antihypertensive effects in spontaneously hypertensive rats (SHR) of a series of 2-(cycloalkylalkynyl)adenosines (2-CAAs) and their congeners are described. The structure-activity relationship of this series of compounds is discussed, focusing on the length of the alkynyl side chain and bulkiness of the terminal cycloalkyl substituents in terms of binding activity and cardiovascular effects. All the 2-CAAs had a preferential affinity for A2 receptors. Of these derivatives, 2-(3-cyclopentyl-1-propyn-1-yl)adenosine (10b) exhibited the most selective affinity for A2 receptors (Ki ratio: A1/A2 = 70) on the basis of receptor binding. In the C-2 binding region of adenosine, compounds often have potent and/or selective A2 activity from introduction of an acetylenic group at the C-2 position followed by one methylene residue further followed by a hydrophobic substituent such as a cycloalkyl ring at the terminal position of the alkynyl side chain. Intravenous injection of 10b up to 100 micrograms/kg had a potent hypotensive effect without a marked decrease in heart rate in anesthetized SHR. Compounds 10j-s, with a hydroxyl group in the C-3" position of the alkynyl side chain, had a potent affinity for both A1 and A2 receptors, but they were not highly selective for A2 receptors. These compounds caused a marked bradycardia upon intravenous administration in anesthetized SHR. Oral administration of 10b (0.1-1 mg/kg) had a potent and long-lasting antihypertensive effect in conscious SHR.

Adenosine↗

PubMed1992

Antitumor activity of a novel nucleoside, 2'-C-cyano-2'-deoxy-1-beta-D-arabinofuranosylcytosine (CNDAC) against murine and human tumors.

The antitumor effects of 2'-C-cyano-2'-deoxy-1-beta-D- arabinofuranosylcytosine (CN-DAC), a synthetic 1-beta-D-arabinofuranosyl-cytosine (ara-C) derivative, were examined and compared with that of ara-C in murine tumors and in various human tumors using three different chemosensitivity tests. CNDAC extended the life span of mice bearing P388 leukemia. CNDAC had a unique in vitro antitumor spectrum for human cancers different from that of ara-C. Compared with ara-C, CNDAC was more effective in 10 human tumors (2 lung, 4 stomach and 4 osteosarcoma), equal in 2 tumors (lung and fibrosarcoma) and less potent in 11 tumors (4 lung, 4 osteosarcoma, bladder, renal and epidermoid). Characteristically CNDAC showed excellent activities against tumors, refractory to ara-C, such as HT-1080 human fibrosarcoma implanted in chick embryos or athymic mice, although its cytotoxicity against HT-1080 was almost equal to that of ara-C. Thus, CNDAC is an interesting and promising agent that should be considered for further detailed preclinical evaluation.

Animals↗

PubMed1992

The synthesis and properties of oligodeoxyribonucleotides containing N6-methoxyadenine.

Oligodeoxyribonucleotides containing N6-methoxyadenine (M) have been synthesized. The order of stability of duplexes consisting of synthesized oligodeoxyribonucleotides, 5'd(CCTGGTAXCAGGTCC)3'-5'd(GGACCTGNTACCAGG)3' (X = M, A, G. N = A, G, T, C), was M: A (Tm = 52 degrees C) greater than M: T (50 degrees C) greater than M: G (48 degrees C) greater than M: C (46 degrees C) observed by thermal denaturation in a buffer of 0.01 M Na cacodylate, and 0.1 M NaCl at pH 7.0. The Tms are within a range of 6 degrees of difference, which is smaller than those of Tms of the duplexes containing A:N pairs (11 degrees) and G:N pairs (11 degrees). DNA replication study on a template-primer system, 5'd(32p-CAGCTTTCGC)3' 3'd(GTCGAAAGCGMAGTCG)5', showed that TTP and dCTP were incorporated into DNA strands at a site opposite to M by Klenow DNA polymerase, but dATP and dGTP were not.

Adenine↗

PubMed1992

Molecular cloning of acetyl coenzyme A: deacetylcephalosporin C o-acetyltransferase cDNA from Acremonium chrysogenum: sequence and expression of catalytic activity in yeast.

Acetyl CoA: deacetylcephalosporin C o-acetyltransferase(DCPC-ATF) catalyses the final step in the biosynthesis of cephalosporin C, the conversion of deacetylcephalosporin C to cephalosporin C. A cDNA encoding DCPC-ATF has been isolated from a cDNA library of a cephalosporin C producing fungus Acremonium chrysogenum using oligonucleotide probes based on N-terminal amino acid sequences of the enzyme. The cDNA contains a single large open reading frame for a putative precursor consisting of 12 amino acid(AA) leader peptide of unknown function, 274 AA large subunit and 126 AA small subunit at the carboxyl end. The cDNA was expressed in yeast exhibiting a functional DCPC-ATF activity. It was also indicated that the leader peptide was not essential for expression of the enzyme activity. The primary structure of DCPC-ATF shows significant homology with those of acetyl CoA: homoserine o-acetyltransferase in Saccharomyces cerevisiae and Ascobolas immersus.

Acetyltransferases↗

PubMed1992

Genetic analysis of HLA class II alleles and susceptibility to type 1 (insulin-dependent) diabetes mellitus in Japanese subjects.

Although HLA-DQB1 alleles encoding aspartic acid at position 57 (Asp-57) are protective against Type 1 (insulin-dependent) diabetes mellitus in Caucasians, most Japanese Type 1 diabetic patients carry at least one Asp-57 DQB1 allele. We analysed the DRB1, DQA1 and DQB1 genes of 99 Japanese patients and 86 control subjects with polymerase chain reaction and sequence-specific oligonucleotide hybridization. We found that (1) the DQA1*0301 allele was significantly increased in Type 1 diabetic patients (RR7.8, pc less than 0.0001); (2) the DRB1*0405 (Dw15) allele, which is a subtype of DR4 haplotype, was significantly increased in DR4-positive patients (RR 12.0, pc less than 0.001); and (3) although the DRw8-DQw8 haplotype was positively associated with Type 1 diabetes, the DRB1*0406-DQw8 haplotype was decreased in the diabetic patients. These data indicate that DRB1 and DQA1 genes also confer susceptibility to Type 1 diabetes in Japanese.

Alleles↗

PubMed1992

A hematological remission by clonal hematopoiesis after treatment with recombinant human granulocyte-macrophage colony-stimulating factor and erythropoietin in a patient with therapy-related myelodysplastic syndrome.

We treated a patient with therapy-related myelodysplastic syndrome (MDS) with human recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (Epo). The patient achieved a hematological remission which continued for more than 16 months despite discontinuation of the treatment. Before the treatment with GM-CSF and Epo the patient had severe pancytopenia, required frequent red cell transfusions, and experienced episodes of severe infection, but after the therapy he no longer needed transfusion and no longer had the infection. While the patient remained in hematological remission, bone marrow examination revealed trilineage dysplasia, and cytogenetic analysis showed an abnormal karyotype [48, XY, +8, +der(1q5p)] in 100% of the metaphases examined. These findings suggest that the hematological remission of this patient may not result from the recovery of the non-clonal hematopoiesis of a normal clone, but result from the monoclonal hematopoiesis of a neoplastic clone.

Blood Cell Count↗

PubMed1992

Glucose tolerance and insulin response in parents of patients with insulin-dependent and juvenile-onset non-insulin-dependent diabetes mellitus.

Glucose tolerance and insulin response were examined using a 100 g oral glucose tolerance test (OGTT) in 108 parents of 23 patients with insulin-dependent (IDDM) and 31 patients with non-insulin-dependent diabetes mellitus (NIDDM), whose age of onset of diabetes was less than 35 years. Thirty-two age-matched healthy volunteers without a family history of diabetes were also examined as a control group. Diabetes and impaired glucose tolerance (IGT) were significantly more frequent in parents of NIDDM (diabetes 34%, IGT 27%) than in parents of IDDM (diabetes 7%, IGT 13%) (P less than 0.001). At least one parent had diabetes or IGT in 30% of IDDM and 84% of NIDDM patients (P less than 0.001), and both parents had diabetes or IGT in 9% of IDDM and 39% of NIDDM patients (P less than 0.02). Even in cases with 'normal' glucose tolerance, the mean plasma glucose was higher in parents of NIDDM than in control subjects, suggesting a high prevalence of abnormal glucose tolerance including the marginal degree of abnormality in the families of NIDDM. The early phase insulin response was decreased more among parents of NIDDM with the greater impairment of glucose tolerance. However, among those with 'normal' glucose tolerance, early phase insulin response did not differ between parents of IDDM and NIDDM, and control subjects. The results confirmed a stronger familial background in NIDDM patients of younger onset than in IDDM. The different patterns of glucose tolerance among two parents of young-onset NIDDM patients suggest heterogeneity of the mode of inheritance of NIDDM among families.

Adult↗

PubMed1992

Antiviral activities of ribavirin, 5-ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide, and 6'-(R)-6'-C-methylneplanocin A against several ortho- and paramyxoviruses.

5-Ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide (EICAR) and 6'-(R)-6'-C-methylneplanocin A (TJ13025) are two novel antiviral agents which are targeted against IMP dehydrogenase and S-adenosylhomocysteine hydrolase, respectively. These compounds have been examined for their activities against various strains of orthomyxoviruses (influenza virus) and paramyxoviruses (parainfluenza virus, mumps virus, measles virus, and respiratory syncytial virus) in vitro. EICAR was 10- to 59-fold more active than ribavirin and TJ13025 was 32- to 330-fold more active than ribavirin against parainfluenza virus types (2 and 3), mumps virus, and measles virus. EICAR was also more active than ribavirin against respiratory syncytial virus and influenza virus, whereas TJ13025 was virtually inactive against these viruses. The 50% virus-inhibitory concentrations of EICAR and TJ13025 were generally within the 0.1- to 1-microgram/ml range. Although the compounds did not prove cytotoxic to stationary host cells (HeLa, Vero, MDCK, and LLCMK2) at a concentration of 200 micrograms/ml, concentrations of 4 to 13 micrograms/ml inhibited the growth of dividing cells. EICAR and TJ13025 should be further pursued as candidate drugs for the treatment of ortho- and paramyxovirus infections.

Adenosine↗

PubMed1992

[Effects of an essential trace element agent (TE-5) for total parenteral nutrition on the mineral nutrition in rats fed a trace element-deficient diet].

TE-5 is an essential trace element agent containing iron, zinc, copper, manganese and iodine for total parenteral nutrition (TPN). We have already reported that TE-5 improved the reduction of trace element concentrations induced by TPN. However, effects of TE-5 on the changes in biological function relating to trace elements are poorly understood. The present study was designed to clarify the effects of TE-5 on these functions. Rats fed a trace element (iron, zinc, copper, manganese and iodine)-deficient diet for 7 weeks showed reductions in the following parameters: plasma and various tissue concentrations of iron, zinc, copper, manganese and iodine, growth rate, erythrocyte (iron), hemoglobin (iron), hematocrit (iron), mean corpuscular constants (iron), plasma alkaline phosphatase activity (zinc), serum ceruloplasmin concentration (copper), liver pyruvate carboxylase activity (manganese) and serum thyroxine concentration (iodine). On the other hand, when TE-5 (0.008, 0.04 and 0.2ml/kg: x 0.2, x 1 and x 5 the usual clinical dose, respectively) was intravenously administered once a day for 7 weeks under the conditions described above, there was a tendency to prevent the reductions of plasma and various tissue concentrations of iron, zinc and manganese. In addition, TE-5 prevented the reductions of growth rate, iron metabolism functions, plasma alkaline phosphatase activity, serum ceruloplasmin concentration and liver pyruvate carboxylase activity. The present study shows that TE-5 prevents both reductions of trace element contents and trace element-related functions, and suggests that TE-5 is useful for treatment of trace element deficiency in TPN.

Animal Nutritional Physiological Phenomena↗

PubMed1992

Purification of acetyl coenzyme A: deacetylacephalosporin C O-acetyltransferase from Acremonium chrysogenum.

Acetyl CoA: deacetylcephalosporin C O-acetyltransferase, which catalyzes the final step of the biosynthetic pathway to cephalosporin C, was stabilized by a buffer solution containing 7-aminocephalosporanic acid and purified over 1300-fold from Acremonium chrysogenum. The purified enzyme has a molecular weight of 55,000 as measured by gel filtration. SDS-polyacrylamide gel electrophoresis showed two subunit bands corresponding to molecular weights of 27,000 and 14,000. The enzyme has an isoelectoric point at pH 4.0 and optimum activity at pH 7.5.

Acetyltransferases↗

PubMed1992

Synthesis of 3'-substituted-2',3'-deoxy-2'-methylidenepyrimidine nucleosides.

2'-deoxy-2'-methylideneuridine derivative 9 was converted into 2',3'-didehydro-2',3'-dideoxy-2'-phenyl-selenomethyl derivative 16, which was treated with NCS and tert-butyl carbamate to afford 3'-amino derivative 18 via a [2,3]-sigmatropic rearrangement. Treatment of 9 with DAST gave a mixture of 2',3'-didehydro-2', 3'-dideoxy-2'-fluoromethyl derivative 19 and 3'-"up"-fluoro-2'-methylidene derivative 20 in a ratio of 1.5 : 1. On the other hand, when 12 was treated with DAST, 19 and 3'-"down"-fluoro-2'-methylidene derivative 21 were obtained in a ratio of 1 : 1.6. These nucleosides were converted into the corresponding cytidine derivatives 4, 6, and 8, respectively. The reaction mechanisms as well as biological activity of these compounds will also be discussed.

Deoxycytidine↗

PubMed1992

[Pulmonary arteriography and bronchial arteriography in pulmonary embolism].

Pulmonary arteriography is the most reliable technique for evaluation of pulmonary embolism and other vascular abnormalities. A definitive diagnosis of pulmonary embolism is made on the basis of direct angiographic signs of emboli of intravascular filling defect and vessel cut-off sign. To obtain these findings, pulmonary arteriography needs to be performed as soon as possible, and in acutely ill patients who are in shock and under consideration for thrombolytic therapy or emergency embolectomy, the study should be performed on an emergency basis. Digital subtraction pulmonary angiography may be an useful technique for massive pulmonary embolism, but it cannot exclude clinically important peripheral pulmonary embolism. Wedged pulmonary arteriography can demonstrate the direct signs of distal emboli, which are difficult to obtain by main pulmonary artery injection angiogram. In the chronic stage of pulmonary embolism, bronchial arteriogram shows collaterals to pulmonary arteries. This study may be useful in patients with chronic pulmonary embolism, especially when thromboembolectomy is planned.

Angiography, Digital Subtraction↗

PubMed1992

[Hairy cell leukemia successfully treated with deoxycoformycin].

A 45-year-old male was hospitalized on September 2, 1989 with chief complaints of general fatigue and fever. Physical examination revealed hepatomegaly and massive splenomegaly. Laboratory tests on admission showed Hb of 7.5g/dl, PLT 4.8 x 10(4)/microliters and WBC 9,610/microliters with 81% hairy cells. Bone marrow aspirate demonstrated 55.1% hairy cells and moderate myelofibrosis. Cytochemically, hairy cells were positive for tartrate-resistant acid phosphatase (TRAP). Surface markers were SmIg G+ A+ kappa +, CD11b+, CD11c+, CD19+, CD20+, CD21-, CD25+, HC2+, HLA-DR+. From these findings, a diagnosis of hairy cell leukemia (HCL) was made. After administration of deoxycoformycin (DCF) at a dose of 5.0mg/m2 1-2 times monthly, splenomegaly disappeared, as did hairy cells from the peripheral blood. Hematological level returned to within normal range except for the presence of 1.2% hairy cells and mild myelofibrosis in bone marrow aspirates. DCF has so far been effective for this patient. While DCF has been reported to be effective in the treatment of HCL in the West, it has not been determined in Japanese patients with HCL, who have different hematologic features from those of HCL patients in the West.

Humans↗

PubMed1991

2-Chlorodeoxyadenosine inhibits the repair of DNA double-strand breaks and does not inhibit the repair of DNA single-strand breaks in X-irradiated Chinese hamster V79 cells.

The exposure of log-phase Chinese hamster V79 cells to 2-chlorodeoxyadenosine (CdA) for 3 h after X irradiation enhanced the lethal effects of X-rays in a concentration-dependent manner. The enhancement of the killing efficiency of X-rays by CdA was mainly observed in the reduction of quasi-threshold doses (Dq) of the dose-response curves. When the ability of CdA to inhibit the repair of X-ray-induced double- and single-strand breaks (dsb and ssb) of DNA was investigated by neutral- and alkaline-filter elution techniques, respectively, it was observed that 90% of dsb were rejoined in the absence of CdA within 30 min after X irradiation and 15-40% of dsb rejoining was suppressed by co-incubation of the cells with 5-10 microM of CdA for 3 h after X irradiation, whereas almost 100% of ssb were rejoined within 15 min regardless of the presence or absence of CdA. From these results it was concluded that CdA interfered exclusively with the repair of DNA dsb in X-irradiated Chinese hamster V79 cells and thereby increased the lethality of X-rays.

2-Chloroadenosine↗