Biomedical subjects

K Yano

Publications and source records attributed to K Yano.

At least 307 records · Page 17Linked to original sources

PubMed1996

Antirheumatic agents. I. Novel methotrexate derivatives bearing an indoline moiety.

Various novel methotrexate (MTX) derivatives bearing an indoline moiety were synthesized and tested for biological activities using human peripheral blood mononuclear cell (hPBMC) and human synovial cells (hSC) derived from patients with rheumatoid arthritis (RA). Compounds having potent activity in vitro were further evaluated using an adjuvant arthritis model in vivo. N-[1-(2,4-Diamino-6-pteridinylmethyl)indoline-5-carbonyl]-L-glutam ic acid 2f showed more potent activities than MTX in vitro and in vivo, and N-[1-(2,4-diamino-6-pteridinylmethyl)-indoline-5-carbonyl]-L-2-ami noadipic acid 2d exhibited fairly good activities in vitro and considerable activity in vivo. Compound 2d was, as expected, not sensitive to folyl-polyglutamate synthetase (FPGS) and did not undergo polyglutamation, a process which may be responsible for a side-effect during MTX therapy.

Animals↗

PubMed1996

Antirheumatic agents. II. Novel methotrexate derivatives bearing an alkyl-substituted benzene ring.

Novel methotrexate (MTX) derivatives with either a mono- or dialkyl-substituted benzene ring were synthesized and initially tested for in vitro anti-proliferative activities using human peripheral blood mononuclear cells (hPBMC) derived from healthy volunteers and synovial cells (hSC) derived from patients with rheumatoid arthritis (RA). Compounds with potent activities were further evaluated in an in vivo adjuvant arthritis model. In comparison with MTX, a glutamate derivative 3a was more potent as a suppressor of the in vitro cell proliferation and the in vivo experimental arthritis, and a homoglutamate derivative, 3e, exhibited fairly good activities in vitro and considerable activity in vivo in a dose-dependent manner. As expected, 3e did not act as a substrate of folylpolyglutamate synthetase (FPGS), and thus did not undergo polyglutamation, which is thought to be responsible for side-effects that occur during MTX therapy.

Antirheumatic Agents↗

PubMed1996

In vitro stability and in vivo absorption studies of colloidal particles formed from a solid dispersion system.

We investigated the physicochemical and pharmaceutical properties of a solid dispersion (SD) derived from a solution of the poorly water-soluble drug (R)-1-[2,3-dihydro-1-(2'-methylphenacyl)-2-oxo-5-phenyl-1H-1, 4-benzodiazepin-3-yl]-3-(3-methylphenyl)urea (YM022), hydroxypropylmethylcellulose 2910 (TC-5E) and polyoxyethylene hydrogenated caster oil 60 (HCO-60). Colloidal particles produced when the SD was dispersed into water had a mean diameter of 160 nm and contained 67-77% YM022. Powder X-ray diffractometry showed that YM022 existed in the colloidal particles in an amorphous state. The particle diameter and YM022 content remained unchanged during storage for 7 d, confirming that the colloidal solution was stable. On oral administration to rats, good absorption was observed for both the colloidal solution prepared immediately before and the sample stored for 7 d before administration. Thus, the stability of this colloidal solution of SD was confirmed by in vitro storage tests and by in vivo absorption experiments in rats.

Absorption↗

PubMed1996

[Crystal forms, improvements of dissolution and absorption of poorly water-soluble (R)-1-[2,3-dihydro-1-(2'-methylphenacyl)-2-oxo-5-phenyl-1H-1, 4-benzodiazepin-3-yl]-3-(3-methylphenyl)urea (YM022)].

Polymorphs of (R)-1-[2,3-dihydro-1-(2'-methylphenacyl)-2-oxo-5-phenyl-1H-1,4- benzodiazepin-3-yl]-3-(3-methylphenyl)urea (YM022) were investigated. Two crystalline forms (alpha- and beta-forms) of YM022 were confirmed by powder X-ray diffractometry and differential scanning calorimetry. alpha- And beta-forms were obtained by recrystallization from ethanol and ethanol: water (5:1), respectively. Amorphous YM022 was obtained by spray drying of YM022 methanol solution. Since both crystalline and amorphous YM022 were sparingly soluble in water, solubilization of YM022 by solid dispersion and wet grinding methods were performed. In vitro dissolution study and in vivo absorption study in dogs were carried out using spray-dried solid dispersion, heat-treated solid dispersion and mechanical mixture. Spray-dried solid dispersion and heat-treated solid dispersion showed enhanced bioavailability, whereas mechanical mixture showed no improvement.

Animals↗

PubMed1996

[The affinities of mosapramine for the dopamine receptor subtypes in human cell lines expressing D2, D3 and D4 receptors].

The affinities of mosapramine hydrochloride, an iminodibenzyl antipsychotic drug, for dopamine receptor subtypes were determined by human dopamine D2, D3 and D4 receptors expressed in several cell lines and compared with those of other neuroleptics. Tritiated spiperone bound to the membrane of transfected cells in a saturable manner, and the Kd values for dopamine D2, D3 and D4 receptors were 0.021, 0.12 and 0.10 nM, respectively. Mosapramine showed the highest affinities for these receptor subtypes among the antipsychotics tested. The ratio of Ki values between D2 and D3 (D2 Ki/D3 Ki ratio) in mosapramine was higher than that of haloperidol, indicating that the effects of mosapramine on D3 receptors were more potent than those of haloperidol. On the other hand, clozapine, risperidone and raclopride had higher affinity to D4, D2 and D3 subtypes, respectively. The affinities of mosapramine for D4 receptors was 8 times higher than that of clozapine, and the affinity for D3 receptors was 40 times higher than that of raclopride. These results suggest that the effect on D3 receptors may underlie at least a portion of mosapramine's atypical clinical profile.

Antipsychotic Agents↗

PubMed1996

Dipeptidyl aminopeptidase IV from Pseudomonas sp. WO24.

Dipeptidyl aminopeptidase IV from Pseudomonas sp. WO24 was purified as two molecular forms of 84 and 82-kDa by SDS-PAGE. Peptide mapping and N-terminal sequence analyses indicated that both proteins might be derived from the same protein, and that the 82-kDa molecule might be a truncated form from the 84-kDa molecule at least at the N-terminus. The DAP IV gene of Pseudomonas sp. WO24 was cloned and expressed in E. coli. The enzyme expressed in E. coli JM109 harboring a hybrid plasmid, pYO-6A, with about a 3-kbp fragment containing the DAP IV gene, was purified with an activity recovery of 24%. The recombinant enzyme also had the same two molecular forms, though the ratio of the two forms (about 1:1) was different from that of the native ones (about 1:4). The native and recombinant enzyme preparations had similar specific activities, suggesting that the 84 and 82-kDa molecules are in an active form and have almost the same specific activity. The molecular mass, the subunit number, the substrate specificity, and the effects of various inhibitors of the native enzyme indicated that this enzyme was a typical DAP IV and had properties similar to those of Flavobacterium meningosepticum rather than others.

Amino Acid Sequence↗

PubMed1996

Microbial flora in the acute phase of periodontitis and the effect of local administration of minocycline.

Periodontitis, similar to other infectious diseases, is known to progress as chronic inflammation with recurrent acute phases. The purpose of this study was to clarify the microbiological composition of the acute phase and to compare the bacterial flora with that of comparable chronic periodontal pockets. We also evaluated the effect of application of minocycline gel locally on the change in the microflora in the acute pockets. Microbial flora from the subgingival pockets of 28 patients in the acute phase of periodontitis and of 12 patients in a comparable chronic phase as the control were investigated by various bacterial culture methods including TS blood agar and TSBV plates. Minocycline gel was applied to the acute periodontal pockets. Changes in the microbiological proportion and clinical parameters at one week after baseline examination were followed by dark-field analysis, culture method, and indirect immunofluorescence technique. Characteristic features of bacterial proportions in the acute site were observed as an increase in Bacteroides forsythus. The number of Porphyromonas gingivalis and black pigmented anaerobic rods also increased. Application of minocycline gel in the acute pocket without any debridement produced improvement in clinical symptoms at one week. Black-pigmented anaerobic rods, P. gingivalis, and B. forsythus decreased significantly at one week after the application. Results indicate that periodontopathic bacteria including B. forsythus and P. gingivalis were predominant in the acute phase of periodontitis and a locally delivered antibiotic may be effective as an alternative modality of treating the acute inflammation.

Acute Disease↗

PubMed1996

Effects of eel neuropeptide Y on ion transport across the seawater eel intestine.

A neuropeptide Y (eNPY) was isolated from the intestinal extract of eels. This peptide enhanced significantly the serosa-negative transepithelial potential difference (PD) and short-circuit current (Isc) across the intestine of the seawater eel after pretreatment with isobutylmethylxanthine, serotonin and methacholine. The effects of eNPY on the Isc were concentration-dependent with a threshold concentration of 3 x 10(-9) M and a maximal effect at 3 x 10(-7) M. Similar concentration-response curve was obtained by porcine peptide YY (pPYY). Since 9 amino acid residues are replaced in the pPYY, this result indicates that these substitutions do not change the potency and the efficacy. These stimulatory actions of eNPY were not blocked by tetrodotoxin, an inhibitor of neural firing, or yohimbine, an alpha 2-adrenoceptor antagonist, indicating that eNPY acts without enteric neural firing or catecholamine release. When eNPY and adrenaline (AD) were applied simultaneously, the effects were additive only at lower dosage (3 x 10(-8) M for eNPY, 3 x 10(-8) M for AD), but not at high dosage (10(-6) M eNPY, 10(-7) M AD). The ceiling effect at high dosage suggests that these two regulators act through common signal transduction systems and affect the Na(+)-K(+)-Cl- cotransport system, since both effects were completely blocked by bumetanide, a specific inhibitor of Na(+)-K(+)-Cl- cotransporter.

Amino Acid Sequence↗

PubMed1996

Impaired glucose tolerance, diabetes, and cardiovascular disease risk factor profiles in the elderly. The Honolulu Heart Program.

OBJECTIVE: The relationship between glucose tolerance status and other cardiovascular disease (CVD) risk factors was evaluated in a cohort of Japanese-American men (n = 3,741) ages 71-93 years who participated in the fourth examination of the Honolulu Heart Program in 1991-1993. RESEARCH DESIGN AND METHODS: In this cross-sectional study, subjects were classified by reported diabetes and glucose tolerance status using questionnaires and the World Health Organization (WHO) criteria, respectively. RESULTS: The prevalence of reported diabetes was 17%. Among the men who completed an oral glucose tolerance test and had no history of diabetes (n = 1,900), 23% were diagnosed as diabetic and 39% had impaired glucose tolerance (IGT) by WHO criteria. The CVD risk factor profiles of men with IGT and diabetes were significantly more adverse compared with men with normal glucose tolerance after adjustment for age. The rates of hypertension, mean levels of BMI, waist-to-hip ratio, triglycerides, and fasting insulin were higher in men with IGT and diabetes compared with normal subjects. Opposite trends were observed for HDL cholesterol. Two-hour insulin was significantly higher among men with IGT and previously undiagnosed diabetes. Men with known diabetes had a lower physical activity index and higher fibrinogen levels than normal subjects. No significant differences were observed for current smoking and alcohol intake. Differences in risk factor levels by glucose tolerance status remained after adjustment for age, physical activity, BMI, and waist-to-hip ratio. CONCLUSIONS: These findings show that among elderly men of Japanese ancestry, impaired glucose tolerance and undiagnosed and known diabetes are highly prevalent, and these conditions are associated with adverse CVD factor profiles.

Age Factors↗

PubMed1996

[Evaluation of non radioactive DNA probe (Affirm DP) for detecting periodontopathic bacteria].

The purpose of this investigation was to evaluate the potential of application of non-radioactive DNA probe method (Affirm DP) in clinical diagnosis and evaluation of treatment efficacy. Sensitivity and specificity of two different cut-off levels (10(4), 5 x 10(5)) of the method with bacterial culture in detection of Bacteroides forsythus, Porphyromonas gingivalis, and Actinobacillus actinomycetemcomitans were compared. Those bacteria were obtained from bacterial cultures and clinical samples from healthy subjects and patients with periodontal disease. The results showed that detection percentage of DNA probe method with 10(4) cut-off was equal to or higher than the culture method for Bacteroides forsythus and Porphyromonas gingivalis detection. Therefore, it is suggested to be a useful chairside DNA probe kit as an aid in clinical diagnosis and evaluation of treatment efficacy.

Aggregatibacter actinomycetemcomitans↗

PubMed1996

Orthotopic liver transplantation for primary hepatic cancer in rats.

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Animals↗

PubMed1996

[Signal transduction system in cardiac cells].

The electrical excitation and conduction in the heart is due to ionic events via ion channels and gap junctions. Function of these channels and gap junctions is regulated by intracellular milieu, which is regulated by many kinds of receptors through intracellular second messengers i.e.; GTP binding proteins, protein kinases, Ca2+ concentrations, H+ concentration, cyclic nucleotides and triphosphate nucleotides. In this paper, we focus on signal transduction systems in cardiac myocytes. Subsequently, some of interactions between signal transduction systems are introduced.

Cyclic AMP↗

PubMed1996

[Long-term efficacy of subcutaneous administration of deferoxamine in patients with secondary hemochromatosis].

A number of studies have shown that regular chelation therapy with deferoxamine is effective in patients with secondary hemochromatosis. However, compliance with these regimen is difficult to obtain in most cases because long-term administration is burdensome. In 3 patients, one each with myelodysplastic syndrome, aplastic anemia and thalassemia intermedia, self-administered subcutaneous one-shot administration of deferoxamine at a dose of 500 mg once or twice daily was carried out over a long period. In all three patients serum ferritin level decreased significantly and the progression of hemochromatosis was prevented. Liver density on computed tomography scan also decreased in one patient. This regimen, in which the patient self-administered deferoxamine subcutaneously one or twice a day is seems to be the most practical method to protect against the progression of hemochromatosis.

Aged↗

PubMed1996