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Biomedical subjects

A Matsuda

Publications and source records attributed to A Matsuda.

At least 451 records · Page 25Linked to original sources
PubMed1984

Anti-parasite activity of nucleoside analogues in Leishmania tropica promastigotes.

Many nucleoside analogs were screened for anti-protozoa activity on Leishmania tropica in an in vitro culture system. 3'-Deoxyinosine and several tubercidin derivatives were found to be potent inhibitors for growth of the promastigote form of L. tropica. EC50 value of 3'-deoxyinosine was 4.43 X 10(-7)M. This compound was remarkably less toxic towards mouse mammary tumor FM3A cells (EC50, 1.25 X 10(-4) M). 3'-Deoxyinosine is metabolized by Leishmania promastigote to give 3'-deoxyinosine-5'-monophosphate, 3'-deoxy-adenosine(cordycepin)-5'-mono, di-, and triphosphates. This means that Leishmania can aminate the 6-position of 3'-deoxyinosine-5'-monophosphate, thereby converting it into a highly toxic compound.

Animals↗
PubMed1984

Effect of bestatin on syngeneic tumors in mice.

The antitumor effect of bestatin against syngeneic tumors such as colon adenocarcinoma 26 (colon 26) and myeloid leukemia C1498 ( C1498 ) was investigated. Bestatin effectively inhibited the growth of both tumors in vivo. The inhibition observed for colon 26 was the largest when bestatin was administered on days 1 to 5 after transplantation of the tumor. The inhibition of C1498 was the largest when bestatin was administered on days 7 to 11. In contrast to these results, bestatin was not at all inhibitory to either tumor line in vitro. Thus, the effect of bestatin administration on the functions of the spleen cells of mice bearing tumors was examined. Spleen cells taken from mice bearing colon 26 and C1498 did not neutralize the corresponding tumor. However, when bestatin was administered to these mice, spleen cells from the administered mice did neutralize the corresponding tumor. Bestatin enhanced antibody-dependent cell-mediated cytotoxicity and natural killer cell activity of the spleen cells of colon 26-bearing mice. Further, bestatin did not inhibit the growth of colon 26 in BALB/c nu/nu mice. It was concluded that bestatin exhibits its antitumor effect against colon 26 and C1498 indirectly by immunomodulation via spleen cells and possibly via T cells.

Adenocarcinoma↗
PubMed1983

Nucleosides. 123. Synthesis of antiviral nucleosides: 5-substituted 1-(2-deoxy-2-halogeno-beta-D-arabinofuranosyl)cytosines and -uracils. Some structure-activity relationships.

The syntheses of several 2'-halogeno-5-substituted-arabinofuranosylcytosines and -uracils are described, and relationships of structure to anti herpes virus activity in vitro were examined. Those arabinonucleosides containing the 2'-fluoro function exhibit, generally, more potent anti herpes virus (HSV) activity than do their 2'-chloro of 2'-bromo analogues. The importance of the fluorine in the 2'-"up" (arabino) configuration for enhancement of antiviral effectiveness is demonstrated by the superior activity of 2'-fluoro-5-iodo-ara-C [3a, FIAC] to that of 2'-fluoro-5-iodo-ribo-C. Of all the nucleosides tested herein, FIAC exhibited the most potent in vitro activity against HSV. 2'-Chloro-5-iodo- and -5-methyl-ara-C (3b and 4b) were 37 to greater than 500 times more effective in vitro against HSV type 2 than against type 1, suggesting that these latter derivatives might serve clinically as useful probes to distinguish between HSV types 1 and 2 in the diagnosis of HSV infections in man.

Animals↗
PubMed1983

Mechanism of action of 2',5-difluoro-1-arabinosyluracil.

Results are described which demonstrate that the cytotoxic action of 2',5-difluoro-1-arabinosyluracil (FFara-Ura) involves conversion to the corresponding 5'-phosphate, FFara-UMP, and subsequent inhibition of thymidylate synthetase. The evidence for this is as follows: (a) cells lacking thymidine kinase are 120-fold more resistant to FFara-Ura; (b) FFara-Ura markedly inhibits the incorporation of 2'-deoxyuridine (dUrd) into DNA with little or no effect on 2'-deoxythymidine (dThd) incorporation; (c) FFara-Ura causes changes in deoxynucleoside triphosphate pool sizes, which are characteristic of specific inhibition of dTMP synthetase. Binding and spectroscopic studies demonstrate that FFara-UMP inactivates dTMP synthetase from Lactobacillus casei in a manner analogous to that described for FdUMP. Furthermore, FFara-Ura is not a substrate for the pyrimidine phosphorylases; the significance of this finding with regard to the possible chemotherapeutic utility of FFara-Ura is discussed.

Animals↗
PubMed1983

Plasma levels of glibenclamide in diabetic patients during its routine clinical administration determined by a specific radioimmunoassay.

Plasma concentration of glibenclamide in routine clinical practice was determined by a specific radioimmunoassay. In diabetic patients treated with glibenclamide for a month or longer, the drug level in fasting morning plasma was variable but the mean level paralleled the daily dose. After oral administration of 2.5 mg in healthy and diabetic subjects, the drug level reached peaks in 1.5 hours and declined to the half of the peak level in next 2-3 hours. The plasma glibenclamide profile after oral dose did not differ significantly in patients with secondary failure to the drug. Comparison of a single-dose and divided-dose schedules of 5 mg glibenclamide revealed that plasma drug level increased each time after administration. Plasma glucose and insulin concentrations did not differ significantly at most times of the day but there was a tendency that increment of plasma glucose after meal was suppressed by a dose taken immediately before a meal. The relationship of blood level of glibenclamide to clinical effectiveness may be rather indirect and needs to be elucidated.

Adult↗
PubMed1983

A case of pituitary gigantism who had two episodes of diabetic ketoacidosis followed by complete recovery of diabetes.

A 17-year-old boy with pituitary gigantism who had two episodes of diabetic ketoacidosis is reported. Glucose tolerance and insulin secretion were evaluated before, during and after each episode of ketoacidosis. The patient was 201 cm tall and weighed 137 kg. Before surgery, his plasma growth hormone level was 3,000 ng/ml, glucose tolerance was almost normal and insulin response to glucose load was enhanced. He fell into diabetic ketoacidosis twice; 3 weeks after hypophysectomy and one year later after getting the "flu". On each occasion, insulin treatment was needed only temporarily. After the ketoacidosis improved, glucose tolerance and C-peptide responses became nearly normal. Urine C-peptide was low during and immediately after the second episode, but increased to normal following recovery. It is presumed that a pre-operative compensation for the diabetogenic action of excess growth hormone by hyper-secretion of insulin was broken when superimposed stress was added. This is an example in which subnormal insulin response may not be a prerequisite for the occurrence of a severe diabetic state, and decompensated insulin secretion leading to ketoacidosis may not imply permanent damage to the beta cells.

Adolescent↗
PubMed1983

Arteriosclerosis obliterans in Japanese diabetic patients.

Arteriosclerosis obliterans (ASO) of the lower extremities was found in 32 cases (1.9%) among 1673 Japanese diabetic patients. Comparison with age-and sex-matched control patients revealed that male sex, older age, hypertension and neglect of treatment of diabetes were positively correlated with ASO, but obesity, smoking and hyperlipidemia were not correlated with ASO. Proteinuria, cerebral vascular disease and myocardial infarction were significantly associated with ASO. The arterial pulses of the foot were examined in 451 diabetic patients. The pulse of A. dorsalis pedis was absent in 29 (6.4%) and was significantly related to the clinical signs and symptoms of ASO. The loss of the pulse of A. dorsalis pedis increased with age and was more frequent in men than in women. The results indicate a lower frequency of ASO in Japanese than in Western diabetic patients.

Aged↗
PubMed1983

[Experimentally induced bleomycin pulmonary toxicity--comparison of the systemic (intraperitoneal) and local (intratracheal) administration].

Effect of two methods of the systemic (intraperitoneal) administration and the local (intratracheal) instillation in small animal species for the evaluation of BLM-induced pulmonary fibrosis were compared. The grade of BLM-induced pulmonary fibrosis was different among age, species and strains of animals. This was more distinct in the intraperitoneal administration than in the intratracheal instillation. That is, BLM pulmonary fibrosis was severer in 15 and 30 weeks old ICR mice than in 4 weeks old young mice and also severer in the 15 weeks old ICR mice than in 15 weeks old Wistar rats and Hartley guinea pigs. In strains of mice, ICR and C3H mice were suffered from severer BLM pulmonary fibrosis than C57BL/6, BALB/c and DBA/2 mice. Most of BLM analogs produced pulmonary fibrosis to the same extent between the both methods, but three analogs (A5, B2 and BAPP) produced severe pulmonary fibrosis by intratracheal instillation compared to intraperitoneal administration. Furthermore, the pulmonary fibrosis in the intraperitoneal administration group often occurred in widespread subpleural region and that of the intratracheal group instillation group occurred in localized bronchoalveolar region. These results indicated the difference of pathogenesis of the pulmonary fibrosis between the both methods.

Aging↗