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Biomedical subjects

K Hatayama

Publications and source records attributed to K Hatayama.

At least 37 records · Page 2Linked to original sources
PubMed1991

Comparative studies of some functional and morphological parameters in the livers of germfree, conventional and ex-germfree mice.

Some parameters of hepatic function and morphology were studied to compare germfree (GF) and conventional (CV) BALB/c mice. The levels of lipid peroxide (LPO) and aniline-hydroxylase (AH) activity in the livers and the serum total cholesterol (TC), triglyceride (TG) and phospholipid (PL) were significantly lower in GF than in CV 8-week-old mice. There were no significant differences in the histology and lectin-histochemistry of the livers in the GF and CV mice. On the other hand, in ex-GF mice which were induced by housing 4-week-old GF mice together with age-matched CV mice, the levels of LPO and AH activity in the liver and the serum TC, TG and PL contents increased rapidly within the first week and then approached values almost identical to those in CV mice 4 weeks later (i.e. at 8 weeks of age). The histologic picture of the liver was similar among the GF, CV and ex-GF mice.

Aniline Hydroxylase↗
PubMed1990

Synthesis and platelet aggregation-inhibitory activities of novel 3-(2-oxopropylidene)azetidin-2-one derivatives. I.

Treatment of (E)-3-(2-hydroxypropylidene)-4-methyl-1-phenylazetidin-2-one (11) with 10% Pd/C gave (E)-(12), (Z)-3-(2-oxopropylidene)-4-methyl-1-phenylazetidin-2-one (13), 3,4-cis-(14a) and 3,4-trans-3-(2-oxopropyl)-4-methyl-1-phenylazetidin-2-one (14b). Among them, 12 and 13 were found to show potent inhibitory activities against rabbit platelet-rich plasma aggregation induced by adenosine diphosphate or collagen. Ring-expanded homologous derivatives and an acyclic analogue of 12 were also synthesized and tested for the biological activities. The azetidin-2-one skeleton bearing a 2-oxoalkylidene moiety at the 3 position was found to be essential for the platelet aggregation inhibitory activities of these compounds.

Animals↗
PubMed1990

Studies on topical antiinflammatory agents. V. 17-(Alkylthio)- and methoxyalkanoates of corticosteroids.

As part of our search for new topical antiinflammatory agents, a series of corticosteroid 17-(alkylthio)- and methoxyalkanoate derivatives was prepared and tested for vasoconstrictive activities. Several compounds were proved to have activity superior or comparable to that of 9 alpha-fluoro-11 beta,21-dihydroxy-16 beta-methyl-17 alpha-valeryloxy-1,4-pregnadiene-3,20-dione (betamethasone 17-valerate, BV). Among these compounds, 21-chloro-11 beta-hydroxy-17 alpha-(methylthio)acetoxy-4-pregnene-3,20-dione (5Aa) was found to have the most potent activity, being more active than BV. The structure-activity relationships of the series revealed that introduction of a (methylthio)acetate function into the 17-position as well as the 21-position of corticosteroids was effective for enhancing the topical antiinflammatory activity.

Administration, Topical↗
PubMed1990

Studies on topical antiinflammatory agents. IV. 21-(Alkylthio)acetates and (methylthio)methoxides of corticosteroids.

A series of 21-(alkylthio)acetates and 21-(methylthio)methoxides of corticosteroids were synthesized and examined for vasoconstrictive activities. The activities of seven compounds were equal to or greater than that of 9 alpha-fluoro-11 beta,21-dihydroxy-16 beta-methyl-17 alpha-valeryloxy-1,4-pregnadiene-3,20-dione (betamethasone 17-valerate, BV). Among them, betamethasone 21-(methylthio)acetate 17-propanoate (2Ca) was found to have the most potent activity, which is superior to that of BV. A structure-activity relationship study revealed that substitution of the 21-hydroxy group of corticosteroids with the (methylthio)acetate function is a useful approach for obtaining potent activity.

Administration, Topical↗
PubMed1989

Studies on topical antiinflammatory agents. II. Synthesis and vasoconstrictive activity of 21-substituted corticosteroids with sulfur-containing moieties.

As part of the search for new topical antiinflammatory agents, various 21-substituted corticosteroids having sulfur-containing moieties were prepared and tested for vasoconstrictive activity in humans. A structure-activity relationship study revealed that substitution of the 21-hydroxy group with a lower alkyl-thio group enhanced the activity. The activities of the 21-methylthio (3Ad) and the 21-ethylthio (3Ae) compounds were more potent than that of 9 alpha-fluoro-11 beta,21-dihydroxy-16 beta-methyl-17 alpha-valeroyloxy-1,4- pregnadiene-3,20-dione (betamethasone 17-valerate, BV).

Administration, Topical↗
PubMed1989

Studies on topical antiinflammatory agents. III. Synthesis of 17 alpha-acyloxy-9 alpha-fluoro-11 beta-hydroxy-16 beta-methyl-1,4-pregnadiene-3,20-dione 21-thio derivatives and related compounds.

A series of 21-thio derivatives of 9 alpha-fluoro-11 beta,17 alpha-dihydroxy-16 beta-methyl-1,4-pregnadiene-3, 20-dione 17-esters and related compounds were synthesized and evaluated as topical antiinflammatory agents. These compounds were prepared by the reaction of 9 alpha-fluoro-11 beta,17 alpha,21-trihydroxy-16 beta-methyl-1,4-pregnadiene-3, 20-dione (betamethasone, I) 17-ester derivatives and various mercapto compounds. A structure-activity relationship study revealed that the structural combination of a thio group at the 21-position and an ester group at the 17-position contributed to vasoconstrictive activity. Among these compounds, the 21-methylthio 17-propanoate compound (6) was found to have the most potent activity, being more potent than betamethasone 17-valerate (BV).

Administration, Topical↗
PubMed1987

[A comparative clinical trial with tegafur plus lentinan treatment at two different doses in advanced cancer].

In order to evaluate the clinical efficacy of combined tegafur plus lentinan treatment, a comparative trial was performed on patients with advanced cancer using two different doses, a conventional-dose group and a high-dose group. Thirty-four patients were evaluable in this trial. The doses of medication were 600 mg of tegafur p.o. daily and 1-2 mg of lentinan i.v. weekly in the conventional-dose group, and 1,200-800 mg of tegafur p.o. daily and 4 mg of lentinan i.v. weekly in the high-dose group. The response was evaluated using the criteria of Koyama. The response rates were 14.3% for the conventional-dose group and 25.0% for the high-dose group, although no statistical difference was observed. Acute toxicities such as oppression in the anterior chest and dryness of the throat, which were considered to be probably due to lentinan, were noted in patients given rapid administration with 20 ml of solution. However, these effects disappeared with slow-drip infusion using 100-200 ml of solution. These results suggest that the combined tegafur plus lentinan treatment would be better administered at a dose higher than the conventional one for the treatment for advanced cancers.

Adult↗
PubMed1986

Mechanism of the cytoprotective effect of prostaglandin I2 and its analogue in human platelets.

The responsiveness of washed human platelets to thrombin was well preserved up to 72 and 96 hours, when they were stored at 4 degrees C with prostaglandin I2 (PGI2) and its stable analogue OP-41483, respectively, while the washed platelets stored with sodium citrate completely lost their responsiveness to thrombin at 48 hours. The effect of PGI2 or the analogue on the resting level of intraplatelet Ca2+ concentration ([Ca2+]i) was investigated, utilizing fluorescent Ca2+ indicator quin 2. PGI2 lowered the resting [Ca2+]i in a dose related manner in the presence or absence of the extracellular Ca2+. The similar results were obtained when OP-41483 was added to the quin 2 loaded platelets. From these results, it was concluded that the lowering of the resting [Ca2+]i may be the prerequisite for the cytoprotective effect of PGI2 or OP-41483.

Aminoquinolines↗
PubMed1986

Interrelationship between secretion, protein phosphorylation and intracellular Ca2+ concentration in platelets stimulated by thrombin or thromboxane A2 analogue.

The interrelationship between ATP-secretion, protein phosphorylation and intracellular Ca2+ concentration ([Ca2+]i) was studied in both 32P and quin 2 loaded human platelets stimulated by thrombin or thromboxane A2 analogue (STA2). In platelets stimulated by thrombin, the degree of 47,000 dalton polypeptides (P47) phosphorylation was observed in completely dose-related manner, regardless of the amount of [Ca2+]i. In the same condition, the degree of myosin light chain (P20) phosphorylation, however, was well correlated with ATP secretion and [Ca2+]i, when platelets were stimulated by lower dose of thrombin. The similar results were obtained in platelets stimulated by STA2. These findings suggested that P20, but not P47, phosphorylation in activated platelets is mediated by a rise of [Ca2+]i and is well correlated with the secretory reaction. It was unlikely that P47 phosphorylation plays any role in promoting platelet activation.

Adenosine Triphosphate↗
PubMed1985

Fluorescent Ca2+-indicator quin 2 as an intracellular Ca2+ antagonist in platelet reaction.

Preincubation of fluorescent Ca2+-indicator quin 2 resulted in inhibition on platelet aggregation and secretion in the absence of extracellular Ca2+. And the mechanism of the inhibition was studied. The inhibition by quin 2 of thrombin stimulated aggregation and ATP secretion of human platelets was dose and incubation time dependent and the inhibition was overcome by an addition of CaCl2 to the suspending buffer. Combination of quin 2 and Ca2+-blockers exerted the complete inhibition of the reaction in the presence of extracellular Ca2+. The inhibitory effect was observed when the intracellular concentration of quin 2 exceeds 3 mM, regardless of the initial dose or the preincubation time. The cellular content of ATP was not reduced by loading platelets with quin 2 in the concentration which exerted an inhibitory effect on the platelet reaction. From these observations, it was postulated that the inhibition is due to chelation of intracellular Ca2+ by quin 2 and the application of this agent as an intracellular Ca2+ antagonist was proposed. Also, we discussed the limitations in the use of quin 2 system as an intracellular Ca2+ indicator.

Adenosine Triphosphate↗
PubMed1978

[Studies on the anti-ulcer effects of isoprenyl flavonoids (1). The anti-ulcer effects of isoprenyl chalcone extracted from Sophora subprostrata (author's transl)].

A series of extracted fractions from sophora subprostrata was screened by determining anti-ulcer effects in pylorus ligated and stressed rats. Fr. [C-2] had the most potent anti-ulcer effects of all fractions extracted. Sophoradin and sophoranone which were isolated from Fr. [C-2] were also found to have inhibitory effects on ulcer formation in pylorus ligated and stressed rats. The anti-ulcer effect of sophoradin was relatively potent in comparison with that of sophoranone and/or Fr. [C-2]. The anti-ulcer effect of sophoranone was approximately the same as that of Fr. [C-2]. The authors examined the effects of sophoradin and sophoranone on gastric secretion in pylorus ligated rats. Sophoradin and sophoranone significantly reduced the volume of gastric juice. Sophoradin but not sophoranone inhibited the free and total acid output of gastric juice. The effect of sophoradin was examined on various secretagogues which induced gastric secretions in rats with acute fistula. Sophoradin showed a tendency to inhibit tetragastrin- and insulin-induced gastric acid secretion, but there were no effects on methacholine- and histamine-induced secretions. These results suggest that sophoradin may have marked anti-ulcer and inhibitory effects on gastric secretion.

Animals↗
PubMed1978

A clinical investigation of chronic pancreatitis--comparative study between alcoholic pancreatitis and non-alcoholic pancreatitis--.

An analysis of 89 cases with chronic pancreatitis revealed 56% of chronic alcoholic pancreatitis (AP). The sex ratio was 47 males to 3 females and the mean age at onset was 42.4 years in AP and 49.3 years in chronic non-alcoholic pancreatitis (NAP). The 'total amount' of alcohol consumption was correlated to the onset. In AP, the abdominal pain was apt to relapse and severe in nature, furthermore painless pancreatitis was seen in 6%. The association with diabetes or calcification (38%) were more frequently seen in AP. The calcifications in AP appeared to be smaller in size and distributed diffusely or localized in cephalic portion. A striking frequency of liver dysfunctions (39 cases) were demonstrated, however, cirrhosis was rare in AP. The P-S test dysunctions in NAP were frequently reversible in the follow up study, while even some of chronic asymptomatic alcoholics developed clinical signs of pancreatitis during the observed period and proceeded to definite AP, of whom pancreatic dysfunctions showed fluctuation and eventual progression. In other words, even pain free intervals the pancreatic inflammation in susceptible persons may proceed to ultimated destruction of the pancreas. The fatality from chronic pancreatitis was rare (12.3%), which was related diabetes mellitus.

Adult↗