Biomedical subjects

K Kikuchi

Publications and source records attributed to K Kikuchi.

At least 361 records · Page 20Linked to original sources

PubMed1998

Ulcerative porokeratosis.

A 54-year-old man presented with multiple annular plaques since infancy. During the intake of nifedipine and nitroglycerin over a period of 6 years, reddish, eruptive and ulcerative changes were seen in the pre-existing skin lesions on the penis, scrotum and legs. In addition to a typical cornoid lamella, histological examination revealed a band-like infiltration beneath the epidermis, liquefaction degeneration of the basal cell layer and subsequent coagulative necrosis of the keratinocytes. We review similar ulcerative types of porokeratosis in the literature and discuss the significance of our unusual case.

Histocytochemistry↗

PubMed1998

Atrophic dermatofibrosarcoma protuberans: a case report and review of the literature.

Dermatofibrosarcoma protuberans is not a difficult tumor to recognize because of its characteristic clinical appearance, although some unusual variants have been reported. We describe the atrophic variant of dermatofibrosarcoma protuberans in a 21-year-old female. The lesion was a smooth-surfaced, oval depression on the left subclavicular area, with a violaceous plaque at the center. The suspected clinical diagnosis did not include fibrous tumors, although histological examination showed the typical picture of dermatofibrosarcoma protuberans. Positive CD34 staining was also helpful in the diagnosis. We review 14 cases of the atrophic variant of dermatofibrosarcoma protuberans in the literature. Dermatologists should be aware of this uncommon but characteristic appearance of atrophic dermatofibrosarcoma protuberans.

Adolescent↗

PubMed1998

Localization of pNT22 70 kDa heat shock cognate-like protein in the plasma membrane.

It has been argued that 70 kDa heat shock cognate (hsc73)-like molecules may be expressed on the surface of certain cells, but direct evidence of this has yet to be found. To clarify whether this molecule belongs to hsc73 itself, the membrane protein fraction of Daudi cells was isolated by Triton X-114 phase separation and the reactivity of this membrane protein fraction was assessed with monoclonal antibodies (mAbs) which react with 70 kDa heat shock protein (hsp) family, i.e., NT22, A15 and 3A3. In western blotting analysis, mAb NT22-defined protein (pNT22) was clearly detected as a membrane protein of Daudi cells with an approximate molecular size of 70 kDa, whereas pNT22 was not recognized by anti-cytoplasmic hsc73/hsp72 mAbs A15 or 3A3. By using deleted recombinant hsc73 proteins, it was determined that mAb NT22 recognizes the N-terminal 350-372 amino acid stretches of the hsc73 protein. mAb NT22 also reacted with the cell surface protein of Daudi cells in FACS analysis. Taken together, our present data strongly suggest that pNT22 may be a novel hsc73-like protein that is localized in the plasma membrane.

Antibodies, Monoclonal↗

PubMed1998

Improved nitric oxide detection using 2,3-diaminonaphthalene and its application to the evaluation of novel nitric oxide synthase inhibitors.

A specific and sensitive detection method for nitric oxide (NO) in living cells and tissue culture systems is required in the search for novel NO synthase (NOS) inhibitors. We have improved a fluorometric determination with 2,3-diaminonaphthalene (DAN) by the addition of 2-phenyl-4,4,5,5-tetramethylimidazoline-3-oxide-1-oxyl (PTIO) as an oxidant to form NO2 from NO. This method is 3 times more sensitive than that without PTIO, and is suitable for examining the NOS-inhibitory activity of large numbers of test compounds using a 96-well microplate reader. The improved method was applied to N-monomethyl-L-arginine (L-NMMA) as a known inhibitor and the derivatives of 2-phenyl-1,2-benzisoselenazol-3(2H)-one as teat compounds in order to investigate the effect of these compounds on NO production from activated rat aortic smooth muscle cells. The results obtained indicate that this method is suitable for the rapid assay of large numbers of test compounds.

2-Naphthylamine↗

PubMed1998

Real time measurement of nitric oxide released from cultured endothelial cells.

Direct detection of nitric oxide (NO) is essential for understanding the precise mechanism of its production from endothelial cells. Previously, we developed an NO detection system based on the chemiluminescence reaction between NO and luminol-H2O2. Here, we have applied this system to cultured endothelial cells for the direct and on-time measurement of NO. The perfusate from cultured endothelial cells was continuously mixed with luminol-H2O2. N(G)-monomethyl-L-arginine (L-NMMA) (10(-4) M) decreased the chemiluminescence signal of NO, suggesting the existence of basal NO release. Bradykinin (10(-8) M-10(-6) M) increased the NO signal (10(-6) M; 5.1+/-0.4 fmol/min, corresponding to 1.7 pM in the perfusate), and this was inhibited by 10(-4) M L-NMMA (1.8+/-0.3 fmol/min). These results corresponded to the changes in cGMP levels in RFL-6 cells, which provide an NO bioassay system. We conclude that the luminol-H2O2 system is useful for the direct and continuous measurement of NO from cultured endothelial cells.

Animals↗

PubMed1998

Studies on nonpeptide angiotensin II receptor antagonists. II. Synthesis and biological evaluation of 5H-pyrazolo[1,5-b][1,2,4]triazole derivatives with a C-linked oxygen functional group at the 6-position.

2,7-Diethyl-5H-pyrazolo[1,5-b][1,2,4]triazole derivatives were synthesized and evaluated for activity as angiotensin II receptor antagonists. Replacement of the C-6 hydrogen with C-linked oxygen functional groups led to derivatives with increased in vitro activities. Among these compounds, 2,7-diethyl-5-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H- pyrazolo[1,5-b][1,2,4]triazole-6-carboxylic acid (2d) showed potent, insurmountable antagonism, but had poor oral potency against angiotensin II-induced pressor response in rats. In order to improve the oral activity, the carboxylic acid function of 2d was converted into a double ester. This modification afforded (+/-)-1-[(ethoxycarbonyl)oxy]ethyl 2,7-diethyl-5-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-5H- pyrazolo[1,5-b][1,2,4]-triazole-6-carboxylate (2f), which was orally active in rats, and produced a dose-dependent decrease in blood pressure when administered orally to conscious furosemide-treated dogs, with ca. 3-fold increased potency in comparison with the parent C-6 hydrogen compound.

Angiotensin Receptor Antagonists↗

PubMed1998

Development of a fluorescent indicator for nitric oxide based on the fluorescein chromophore.

Endogenous nitric oxide (NO) appears to modulate many physiological and pathophysiological processes. In order to obtain direct evidence for NO functions in vivo, we have developed 4,5-diaminofluorescein (DAF-2) as a novel fluorescent indicator for NO. Green-fluorescent triazolofluorescein formed by the reaction of NO and DAF-2 affords high sensitivity for NO (detection limit: 5 nM). Membrane-permeable DAF-2 diacetate (DAF-2 DA) was loaded into activated rat aortic smooth muscle cells, where the ester bonds are hydrolyzed by intracellular esterase, generating DAF-2. The fluorescence in the cells increased in a NO concentration-dependent manner. This imaging method should be useful for studies of the dynamic biological actions of NO at the molecular level with fine temporal and spatial resolution.

Animals↗

PubMed1998

Studies on nonpeptide angiotensin II receptor antagonists. I. Synthesis and biological evaluation of pyrazolo[1,5-b][1,2,4]triazole derivatives with alkyl substituents.

Alkyl-substituted pyrazolo[1,5-b][1,2,4]triazole derivatives were synthesized and evaluated for activity as angiotensin II receptor antagonists. Molecules with the (methylbiphenylyl)tetrazole moiety and N-5 were the preferred compounds. Ethyl substitutions at both C-2 and C-7 resulted in the optimal compound, 2,7-diethyl-5-[[2"-(1H -tetrazol-5-yl)biphenyl-4-yl]methyl]-5H-pyrazolo[1,5-b][1,2,4]tria zole (5n), with a pA2 value of 8.774 in rabbit aorta. In the in vivo tests, 5n inhibited the angiotensin II-induced pressor response in rats after oral administration. This compound also produced a dose-dependent decrease in blood pressure when administered orally to conscious furosemide-treated dogs, having a longer duration of action as compared to DuP753. These data suggest that 5a may be a useful agent for the treatment of angiotensin II-dependent disease, such as hypertension.

Administration, Oral↗

PubMed1998

Studies on nonpeptide angiotensin II receptor antagonists. III. Synthesis and biological evaluation of 5-alkylidene-3,5-dihydro-4H-imidazol-4-one derivatives.

5-Alkylidene-3,5-dihydro-4H-imidazol-4-one derivatives were synthesized and evaluated for activity as angiotensin II receptor antagonists. Substitutions at C-2 and C-5, respectively, with a propyl group and a 1-methylethylidene group resulted in the optimal compound, 3,5-dihydro-5-(1-methylethylidene)-2-propyl-3-[[2'-(1H-tetrazol - 5-yl)biphenyl-4-yl]methyl]-4H-imidazol-4-one (2b), with a pA2 value of 8.85 in rabbit aorta. When administered orally to rats, 2b showed a greater inhibitory effect on angiotensin II-induced pressor response than DuP 753. Compound 2b also showed a good antihypertensive effect when administered orally to conscious sodium-depleted spontaneously hypertensive rats, with a duration of action of 24 h. These data suggest that 2b may be a useful agent for the treatment of angiotensin II-dependent diseases such as hypertension.

Angiotensin II↗

PubMed1998

Studies on nonpeptide angiotensin II receptor antagonists. IV. Synthesis and biological evaluation of 4-acrylamide-1H-imidazole derivatives.

A novel series of nonpeptide angiotensin II antagonists containing the acrylamide group at the 4-position of the imidazole ring was synthesized and their antagonistic activity was examined by functional assay in rabbit aorta. The acrylamide group was selected as a large lipophilic surrogate for the chloro group of EXP3174. A structure-activity relationship study of the acrylamide moiety has shown that substitution at the 4-position with the N-methyl-3,3-dimethylacrylamide group resulted in the optimal compound, 2-butyl-4-[(3,3-dimethylacryloyl)methyl-amino]-1-[[2'-(1H-tetra zol-5- yl)biphenyl-4-yl]methyl]-1H-imidazole-5-carboxylic acid (1), which was superior to EXP3174 in vitro. Since 1 showed only poor activity against angiotensin II-induced pressor response in rats after oral administration, the carboxylic acid function of 1 was converted into prodrug esters (13). Among these, the 1-[(ethoxycarbonyl)oxy]ethyl ester (13a) showed the most potent and longest-lasting activity when given orally to rats. When administered orally to conscious furosemide-treated dogs, 13a showed an approximately 3-fold increased hypotensive activity in comparison with DuP 753. These data suggest that 13a may be an useful agent for the treatment of angiotensin II-dependent diseases, such as hypertension.

Acrylamides↗

PubMed1998

A case of cardiac sarcoidosis: significance of ventricular tachycardia originating from the septum.

A 65-year-old woman was admitted for assessment of recurrent tachycardia. Cross-sectional echocardiography showed that the anterobasal portion of the ventricular septum was thin and dyskinetic. An electrophysiologic study revealed ventricular tachycardia, during which marked fragmented potentials could be obtained from the anterior septal aspect of the right ventricle. The site of earliest activation was in the vicinity of the His bundle. A diagnosis of cardiac sarcoidosis was made by based on endomyocardial biopsy combined with the clinical manifestations. Ventricular tachycardia originating from the anterior septum may be an indicator of underlying cardiac sarcoidosis.

Aged↗

PubMed1998

Mechanical stretch activates a pathway linked to mevalonate metabolism in cultured neonatal rat heart cells.

It is not certain whether activation of the Ras/mitogen-activated protein (MAP) kinase pathway is involved in cardiac hypertrophy. 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, such as lovastatin, prevent farnesylation of the Ras protein, which is critical for Ras's membrane localization and function. Therefore, the present study was undertaken to investigate the role of the Ras pathway, which is linked to mevalonate metabolism, in the mechanism of stretch-induced myocyte hypertrophy. Myocytes isolated from 1- to 2-day-old rats were cultured at 4.1 x 10(6) cells per well in a deformable silicon dish and incubated with serum-free medium for 7 days. The cultures were stretched by 15% on culture day 4. Stretch increased the RNA/DNA ratio by 20% to 26% on culture days 5 and 6 and the protein/DNA ratio by 18% to 20% on culture days 6 and 7. Stretch accelerated rates of protein synthesis by 24% on culture day 6. Stretch increased protein kinase C (PKC) activity, MAP kinase activity, and c-fos mRNA expression. A selective PKC inhibitor, calphostin C (1 x 10(-6) M), prevented the stretch-induced increase in PKC activity, but lovastatin (7.5 x 10(-6) M) did not. Lovastatin as well as calphostin C partially but significantly inhibited the stretch-induced increases in MAP kinase activity, c-fos mRNA expression, and protein synthesis. Pretreatment with both lovastatin and calphostin C completely inhibited the increases in these variables caused by stretch. Lovastatin as well as calphostin C prevents stretch-induced cardiac hypertrophy. These results suggest that mechanical stretch may activate the Ras pathway, which is linked to mevalonate metabolism, in cultured neonatal rat heart cells.

Animals↗

PubMed1998

Mechanism of endothelium-dependent vasorelaxation evoked by lysophosphatidylcholine.

Vasorelaxation induced by lysophosphatidylcholine (LPC) and platelet activating factor (PAF) was examined in rings isolated from rat aorta and mesenteric artery. LPC caused dose-dependent vasodilatation, which was sensitive to CV-6209, a PAF antagonist, and NG-monomethyl-L-arginine, a nitric oxide synthase inhibitor, but insensitive to indomethacin. PAF (10(-7)M) caused a tachyphylactic effect in mesenteric artery, but no tachyphylactic effect was demonstrated with LPC. Vasorelaxation patterns with LPC differed from those with PAF in the rat mesenteric artery. These results suggest that LPC-induced vasorelaxation may involve increased nitric oxide production mediated by the PAF receptor pathway, another receptor pathway possibly blocked by CV-6209, or PAF itself produced in endothelial cells in response to LPC.

Animals↗

PubMed1998

[Effect of bisoprolol, a beta 1-selective beta-blocker, on lipid and glucose metabolism and quality of life in elderly patients with essential hypertension].

The present study investigated the effect of bisoprolol, a beta 1-selective beta-blocker without intrinsic sympathomimetic activity (ISA), on lipid and glucose metabolism and quality of life (QOL) in elderly patients with essential hypertention. Bisoprolol at doses of 5-10 mg was administered once daily for 12 weeks to 60 non-elderly and 21 elderly outpatients with mild to moderate essential hypertension. In both groups bisoprolol significantly decreased both systolic and diastolic blood pressures and significantly reduced pulse rates to the same extent. The levels of serum cholesterol, HDL-cholesterol and triglyceride, and the response of plasma glucose and insulin to 75 g oral glucose load, were not changed in either group by the bisoprolol treatment. Bisoprolol significantly improved QOL in both groups. Bradycardia, a side effect attributable to bisoprolol, was noted in only one patient in the elderly group. These results suggest that bisoprolol is a safe and useful antihypertensive drug in elderly and non-elderly patients with essential hypertension.

Adrenergic beta-Antagonists↗

PubMed1998

[Bickerstaff's brainstem encephalitis with one-and-a-half syndrome].

We presented a case of Bickerstaff's brainstem encephalitis. A 50-year-old woman developed semicoma, external ophthalmoplegia, hyporeflexia, extensor plantar responses. A high titer of anti-GQ1b IgG antibody was detected in her acute phase serum. Auditory brainstem response suggested the presence of brainstem lesion. Although MRI and CSF showed no abnormality, one-and-a-half syndrome was observed during the clinical course, suggesting involvement of the pontine tegmentum. She received steroid pulse-therapy and symptoms disappeared completely. Our case suggested that anti-GQ1b IgG antibody might relate to the pathogenesis of intramedullary as well as extramedullary lesions.

Biomarkers↗

PubMed1998

Lifestyle evaluation system to support health education.

A computer-based system for evaluation of one's lifestyle was designed so that public health nurses could use it for health education to improve a patient's lifestyle and to prevent lifestyle-related diseases. The Lifestyle Evaluation System (LES) is a computer program that works on a personal computer. The LES is consist of four parts; inputting personal data, answering the questionnaire, showing the result and getting health check up data. The questionnaire includes 40 questions regarding diet, smoking, drinking, physical activity, rest, social activity and health care activities, based on Breslow's seven lifestyles. The result offers participants' lifestyle evaluation in forms of values, graphs, tables and messages. Evaluation values are deviation value, rank, BMI and standard weight. The LES also offers participant's periodic health check data, average data derived from all residents' data, and past results of LES so that public health nurses are able to use these for health education. The health check data is obtained from another database stored on floppy disks. The participants input data by themselves and get result immediately. The interactive style is effective in raising interest in health education.

Computer Systems↗

PubMed1998

The selective reduction in PTPdelta expression in hepatomas.

The mRNA levels for receptor-like protein tyrosine phosphatases (PTPases), PTPalpha, PTPdelta, PTPgamma and LAR, were evaluated by Northern blot analysis in two types of chemically-induced rat primary hepatomas. In the four PTPases the PTPdelta mRNA was selectively reduced in these hepatoma tissues. It was also diminished in HepG2 hepatoblastoma cell line and in all of the poorly differentiated ascites hepatoma cells examined. PTPalpha, PTPgamma and LAR did not show such a characteristic decrease. This selective reduction in PTPdelta expression strongly suggests PTPdelta plays an important role in hepatocarcinogenesis, possibly as a tumor suppressor gene.

Animals↗

PubMed1998

Increased production of interleukin 6 and interleukin 8 in scleroderma fibroblasts.

OBJECTIVE: To determine additional abnormal characteristics related to cytokines in fibroblasts derived from systemic sclerosis (SSc), we examined the production of interleukin 6 (IL-6) and IL-8 and their mRNA levels both in scleroderma fibroblasts and in those from normal skin. METHODS: Cultured fibroblasts from patients with SSc and healthy controls were examined. Production of IL-6 and IL-8 was assessed by specific ELISA, and the levels of IL-6 and IL-8 mRNA were determined by reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Basal production of both IL-6 and IL-8 was significantly increased in scleroderma fibroblasts compared with controls. When cells were stimulated with either IL-1beta (50 pg/ml) or tumor necrosis factor-alpha (TNF-alpha: 10 ng/ml), the production of IL-6 and IL-8 was predominantly increased in both cell strains and there was no significant difference in the production of IL-6 and IL-8 between them. When normal fibroblasts were stimulated with IL-1beta for 48 h and subcultured, both IL-6 and IL-8 production were significantly increased, and production remained elevated even after 3 passages. RT-PCR revealed that IL-6 and IL-8 mRNA were detected in scleroderma fibroblasts but not in normal skin fibroblasts without cytokine stimulation. When stimulated with IL-1beta, both cell strains expressed IL-6 and IL-8 mRNA to almost the same extent. CONCLUSION: Increased production of IL-6 and IL-8 by scleroderma fibroblasts suggests that these cells may have been stimulated by certain cytokines in vivo.

Cells, Cultured↗