Search PubMed⌕ Search

Biomedical subjects

C Ito

Publications and source records attributed to C Ito.

At least 55 records · Page 3Linked to original sources
PubMed2000

The role of brain histamine in acute and chronic stresses.

As a neurotransmitter or neuromodulator, brain histamine has a variety of physiological roles in brain functions. Acute stress increases the histamine turnovers in the diencephalon, nucleus accumbens and striatum. Histamine regulates anterior pituitary hormones. Anxiolytic drugs also decrease brain histamine turnover. Histamine H1 receptor antagonists and H3 receptor agonists decrease the anxiety state. These findings show that acute stresses increase brain histamine turnover, especially in the diencephalon, which would be partly related to the pathology of anxiety. Moreover, chronic restraint stress continued to increase the histamine turnovers in the nucleus accumbens and striatum, not in the diencephalon. Chronic administration of psychostimulants also increase the striatal histamine release. Histamine agonists prevent psychostimulant-induced behavior and the development of behavioral sensitization. These results indicate that chronic stress continues to increase the histamine turnovers in the nucleus accumbens and striatum, which would have a role of preventing stress vulnerability. Moreover, histamine H3 receptor antagonists have antidepressive effects. Therefore, no increase of histamine turnover in the diencephalon is related to the pathology of depressive state.

Acute Disease↗
PubMed2000

Quantitative study of flavonoids in leaves of citrus plants.

Leaf flavonoids were quantitatively determined in 68 representative or economically important Citrus species, cultivars, and near-Citrus relatives. Contents of 23 flavonoids including 6 polymethoxylated flavones were analyzed by means of reversed phase HPLC analysis. Principal component analysis revealed that the 7 associations according to Tanaka's classification were observed, but some do overlap each other. Group VII species could be divided into two different subgroups, namely, the first-10-species class and the last-19-species class according to Tanaka's classification numbers.

Chromatography, High Pressure Liquid↗
PubMed2000

Antitumor agents. 203. Carbazole alkaloid murrayaquinone A and related synthetic carbazolequinones as cytotoxic agents.

Murrayaquinone A (1) and murrayafoline A (3), isolated from the root bark of Murraya euchrestifolia, were identified as cytotoxic compounds. Murrayaquinone A (1) demonstrated significant cytotoxicity against SK-MEL-5 and Colo-205 cells, with ED(50) values of 2.58 and 3.85 microg/mL, respectively. In contrast, murrayafoline A (3) exhibited marginal or weak cytotoxicity against SK-MEL-5, Colo-205, HCT-8, KB, and A-549 tumor cell lines, with ED(50) values ranging from 5.31 to 7.52 microg/mL. In total, 20 carbazole alkaloids (1-20), isolated previously by Furukawa et al. from various plant sources were also evaluated for their cytotoxic profiles in the NCI's human disease-oriented, 60-cell line, in vitro antitumor screening protocol. Compounds 3 and 15 showed potent cell-line selective cytotoxicity against MOLT-4 cells, with log GI(50) values of -8.60 and -8.49 M, respectively, while 12 demonstrated better selectivity against the colon cancer subpanel. Moreover, synthetic 2-methyl- or 3-methyl-carbazolequinone derivatives with various substituents in the A-ring were evaluated against KB, SK-MEL-5, Colo-205, and HCT-8 tumor cells. 6-Methoxy- (21), 6-methyl- (22), and 6-chloro- (24) 3-methyl-carbazolequinones demonstrated significant cytotoxicity against SK-MEL-5 cells, with ED(50) values of 0.55, 0.66, and 0.83 microg/mL, respectively. Compounds 21 and 22 were also significantly cytotoxic toward KB cells, with ED(50) values of 0.76 and 0.92 microg/mL, respectively, and 21 displayed a similar level of toxicity against Colo-205 cells (ED(50) 0.87 microg/mL).

Alkaloids↗
PubMed2000

Constituents of Boronia pinnata.

A novel quinolone, pinolinone (1); seven new phenylpropanoids, boropinols A (2), B (3), C (4), boropinals A (5), B (6), C (7), and boropinic acid (8); and a new lignan, boropinan (9), were isolated from the roots of Boronia pinnata, and their structures were elucidated by NMR and MS analyses. In a search for novel cancer chemopreventive agents (antitumor-promoters), we screened 10 compounds isolated from the plant for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate in Raji cells. Boropinic acid (8) and 4'-hydroxy-3'-prenylcinnamaldehyde were observed to significantly inhibit the EBV-EA activation.

Alkaloids↗
PubMed2000

Chemical constituents of Clausena excavata: isolation and structure elucidation of novel furanone-coumarins with inhibitory effects for tumor-promotion.

A study of the chemical constituents of the leaves of Clausena excavata cultivated in a greenhouse led to the isolation and identification of 10 new furanone-coumarins named clauslactones A (1), B (2), C (3), D (4), E (5), F (6), G (7), H (8), I (9), and J (10), together with a known carbazole, clauszoline M, and a coumarin, umbelliferone. The new coumarins contain a C(10) terpenoid side chain with a furanone (gamma-lactone) moiety. Further, in clauslactones A-D (1-4), the terpenoid side chain was shown to be linked to the 7,8-dioxygenated coumarin skeleton through a 1, 4-dioxane ring system. This is the first example of coumarins with these structural characteristics in nature. These furanone-coumarins were found to exhibit inhibitory activity against 12-O-tetradecanoylphorbol-13-acetate-induced Epstein-Barr virus early antigen activation in Raji cells.

Anticarcinogenic Agents↗
PubMed2000

Histamine H2 receptor gene variants: lack of association with schizophrenia.

A role of histaminergic neuronal systems in schizophrenia was suggested by an association with several polymorphisms located in the coding region of the histamine H2-receptor (H2R) gene (Orange et al, Mol Psychiatry 1996; 1: 466-469). Using either the reference method of direct sequencing or restriction endonuclease digestion of PCR products amplified from DNA, we could not confirm the existence of these polymorphisms in 53 Swedish controls, 52 French controls and 88 French schizophrenics. In contrast, we detected a G543A transition in the coding region of the gene that was not found in the British population. This allelic variation, which was observed in 15% of the controls with no homozygotes, did not change the amino acid sequence of the receptor. We also analyzed a 1.8-kb nucleotide sequence of the promoter region in which we detected two additional polymorphisms that may modulate the expression of the H2R gene. The first one was a A-592G transition located in the minimal promoter of the gene and found in;10% of controls with no homozygotes. The second one was a G-1018A transition located in an enhancer element of the promoter and was found in;20-30% of controls (with;2-4% homozygotes). DNA analysis of the 88 French schizophrenic subjects revealed that the incidence of the three polymorphisms was not significantly different in this population. In conclusion, the present findings may suggest a surprisingly high variability of the H2R gene polymorphisms in different geographical areas but do not support an association of these allelic variations with schizophrenia.

Female↗
PubMed2000

Erythropoietin regulates vascular smooth muscle cell apoptosis by a phosphatidylinositol 3 kinase-dependent pathway.

BACKGROUND: Recent studies have shown that several cytokines could induce apoptosis in vascular smooth muscle cells (VSMCs) via the induction of nitric oxide (NO). In the present study, we explored whether human recombinant erythropoietin (rHuEPO) has a modulatory effect of apoptosis on interleukin-1beta (IL-1beta) or NO donor sodium nitroprusside (SNP)-induced apoptosis in rat cultured VSMCs. METHODS: The quantitation of apoptosis among VSMCs was assessed by nuclear morphological analysis with fluorescent DNA-binding dye Hoechst 33258. Apoptotic changes were also confirmed by the detection of DNA fragmentation. The expression of EPO receptor (EpoR), cellular protein tyrosine phosphorylation, including EpoR and Janus kinase (JAK) 2, and the association of p85 subunit of phosphatidylinositol 3 kinase (PI3-kinase) to tyrosine-phosphorylated proteins, including EpoR, were explored by using Western blotting analysis combined in part with immunoprecipitation. RESULTS: rHuEPO inhibited the apoptosis induced by IL-1beta or SNP in a dose- and time-dependent manner. The anti-apoptotic effects of rHuEPO were diminished in the presence of a tyrosine kinase (TK) inhibitor genistein or anti-EpoR antibody. After stimulation with rHuEPO, EpoR and JAK 2 were tyrosine phosphorylated, and p85 subunits were associated with EpoR. Also, rHuEPO induced phosphorylation of Akt through a PI3-kinase-dependent pathway. The phosphorylation of Akt and the anti-apoptotic effects of rHuEPO were diminished in the presence of a PI3-kinase inhibitor, wortmannin. CONCLUSION: Our present study demonstrates that rHuEPO inhibites IL-1beta or SNP-induced VSMC apoptosis. The TK-dependent pathway, particularly the PI3-kinase-dependent pathway, seems to be critical to the countervailing effect of rHuEPO on IL-1beta and SNP-induced VSMC apoptosis.

Anemia↗
PubMed2000

The role of PPARgamma as a thrifty gene both in mice and humans.

The biological role of peroxisome proliferator-activated receptor gamma (PPARgamma) was investigated by gene targeting and case-control study of the Pro12Ala PPARgamma2 polymorphism. Homozygous PPARgamma-deficient embryos died at 10.5-11.5 days post conception (dpc) due to placental dysfunction. Heterozygous PPARgamma-deficient mice were protected from the development of insulin resistance due to adipocyte hypertrophy under a high-fat diet, whose phenotypes were abrogated by PPARgamma agonist treatment. Heterozygous PPARgamma-deficient mice showed overexpression and hypersecretion of leptin despite the smaller size of adipocytes and decreased fat mass, which may explain these phenotypes at least in part. This study reveals a hitherto unpredicted role for PPARgamma in high-fat diet-induced obesity due to adipocyte hypertrophy and insulin resistance, which requires both alleles of PPARgamma. A Pro12Ala polymorphism has been detected in the human PPARgamma2 gene. Since this amino acid substitution may cause a reduction in the transcriptional activity of PPARgamma, this polymorphism may be associated with decreased insulin resistance and decreased risk of type 2 diabetes. To investigate this hypothesis, we performed a case-control study of the Pro12Ala PPARgamma2 polymorphism. In an obese group, subjects with Ala12 were more insulin sensitive than those without. The frequency of Ala12 was significantly lower in the diabetic group, suggesting that this polymorphism protects against type 2 diabetes. These results revealed that in both mice and humans, PPARgamma is a thrifty gene mediating type 2 diabetes.

Adipose Tissue↗
PubMed2000

Synthesis and evaluation of novel 2-oxo-1,2-dihydro-3-quinolinecarboxamide derivatives as serotonin 5-HT4 receptor agonists.

A series of N-azabicycloalkyl-1-alkyl-2-oxo-1,2-dihydro-3-quinolinecarboxamides were synthesized and tested for serotonin 5-HT4 receptor-stimulating effects in the regulation of electrically-evoked contraction in guinea pig muscle. Among them, N-azabicycloalkyl-1-isopropyl-2-oxo-1,2-dihydro-3-quinolinecarboxamide (8c, 9c, 10c, 11c, 12c) exhibited potent serotonin 5-HT4 receptor-stimulating activity. The most potent compound, N-(endo-8-methyl-8-azabicyclo[3.2.1 oct-3-yl)-1-isopropyl-2-oxo-1,2-dihydro-3-quinolinecarboxamide (8c, ED50 = 36.3 nMi), was seven times as active as cisapride, while 8c had no affinity for 5-HT1A, 5-HT1D, D2, muscarinic M2 or muscarinic M3 receptors even at 10 microM. Compound 8c stimulated digestive tract motility in conscious fed dogs (1.0 mg/kg p.o.).

Animals↗
PubMed2000

Chemical constituents of Micromelum minutum. Isolation and structural elucidation of new coumarins.

The chemical constituents of an acetone extract of the stems of Micromelum minutum Wight et Arn (Rutaceae), collected at Nakorn-Rachasima province in Thailand, were studied. Six new coumarins, named micromarin-A (1), -B (2), -C (3), -F (4), -G (5), and -H (6), were isolated along with six known coumarins, and their structures were elucidated by chemical and spectroscopic methods.

Coumarins↗
PubMed2000

Chemical constituents of Avicennia alba. Isolation and structural elucidation of new naphthoquinones and their analogues.

Three new naphthoquinones and their analogues, named avicequinone-A (1), -B (2), -C (3), and avicenol-A (4), -B (5), -C (6), respectively, were isolated from the stem bark of Avicennia alba (Avicenniaceae) collected in Singapore, and their structures were elucidated by means of spectral methods. Gillan and co-workers have proposed that the structures of the new phytoalexins isolated from Avicennia marina are 1,2-naphthoquinones 8 and 9. Our synthetic and spectrometric studies showed that these structures should be revised respectively to 1,4-naphthoquinones 2 and 3, named avicequinone-B and -C by us.

Magnetic Resonance Spectroscopy↗
PubMed2000

Four new furanone-coumarins from Clausena excavata.

Four new furanone-coumarins, clauslactones-N (4), -O (5), -P (6) and -Q (7) were isolated from the leaves and twigs of Clausena excavata BURM. f. (Rutaceae) collected in Indonesia and their structures were elucidated by spectroscopic analysis.

4-Butyrolactone↗
PubMed2000

Chemical constituents of Glycosmis citrifolia (Willd.) Lindl. Structures of four new acridones and three new quinolone alkaloids.

The structures of two new dimeric acridone alkaloids, glycobismine-D (1) and -E (2), having a novel linkage as binary acridones, three monomeric acridones, glycocitrine-IV (3), -V (4), and -VI (5), and three quinolone alkaloids, glycocitlone-A (6), -B (7), and -C (8) from Glycosmis citrifolia (Willd.) Lindl. (Rutaceae) have been elucidated by spectrometric studies.

Acridines↗
PubMed2000

Prevalence of diabetes estimated by plasma glucose criteria combined with standardized measurement of HbA1c among health checkup participants on Miyako Island, Japan.

OBJECTIVE: To estimate the prevalence of diabetes in participants of an annual health checkup in the district of the Miyako Public Health Center (Okinawa, Japan) by using the revised criteria of the Japan Diabetes Society (JDS). RESEARCH DESIGN AND METHODS: The subjects studied here were all Japanese and 45-75 years of age at the time of the health examination in 1998. Diagnosis of diabetes was based on the following: 1) fasting plasma glucose > or =7.0 mmol/l, 2) casual plasma glucose > or =11.1 mmol/l, 3) HbA(1c) > or =6.1%, and 4) self-report on a special questionnaire given at the examination. The HbA(1c) value was standardized by the measurement of 2 standard samples provided by the JDS. RESULTS: Among the 2,621 subjects, 59.7% had their fasting blood glucose levels measured. Of the subjects diagnosed as having diabetes, 154 (12.6%) were men and 115 (8.6%) women. Among the subjects newly diagnosed with diabetes from their fasting blood glucose levels. 27.5% of the men and 21.9% of the women had diagnoses based on HbA(1c) alone. Overall, 34.9% of the subjects with newly diagnosed diabetes were identified by plasma glucose (PG) alone and 33.0% were diagnosed by HbA(1c) alone. CONCLUSIONS: The combination of PG and HbA(1c) resulted in a considerable increase in newly diagnosed diabetes as compared with the use of only one of these parameters. Considering the convenience and correlation with vascular complications, use of the 2 tests may be beneficial in epidemiological studies of the Japanese population to identify high-risk groups for micro- and macrovascular diseases.

Aged↗
PubMed2000

[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (1998)].

The bacteria isolated from the patients with lower respiratory tract infections were collected by institutions located throughout Japan, since 1981. Ikemoto et al. have been investigating susceptibilities of these isolates to various antibacterial agents and antibiotics, and analyzed some characteristics of the patients and isolates from them each year. Results obtained from these investigations are discussed. In these 18 institutions around the entire Japan, 532 strains of presumably etiological bacteria were isolated mainly from the sputa of 438 patients with lower respiratory tract infections during the period from October in 1998 to September in 1999. MICs of various antibacterial agents and antibiotics were determined against 85 strains of Staphylococcus aureus, 100 strains of Streptococcus pneumoniae, 96 strains of Haemophilus influenzae, 75 strains of Pseudomonas aeruginosa (non-mucoid strains), 6 strains of Pseudomonas aeruginosa (mucoid strains), 38 strains of Moraxella subgenus Branhamella catarrhalis, 26 strains of Klebsiella pneumoniae etc., and the susceptibilities of 517 strains were assessed except for those strains that died during transportation. S. aureus strains for which MICs of oxacillin (MPIPC) were higher than 4 micrograms/ml (methicillin-resistant S. aureus: MRSA) accounted for 60.0%. Vancomycin (VCM) and arbekacin (ABK) showed the most potent activities against MRSA. But one of MRSA showed resistance to ABK with the MIC of 64 micrograms/ml. The sensitive strains of MRSA to VCM have decreased. The frequency of penicillin (PC)-intermediate S. pneumoniae (PISP) + PC-resistant S. pneumoniae (PRSP) have increased in 46.0% for 1998 comparatively from 30.9% of 1997's. But PRSP decreased, and PISP increased into 39.0% of 1998 years from 19.8% of 1997's. Panipenem (PAPM), imipenem (IPM) and faropenem (FRPM) showed the most potent activities against S. pneumoniae with MIC80s of 0.125 microgram/ml or below. Against H. influenzae and M. (B.) catarrhalis, almost all the drugs showed good activities. The sensitive strains of them against ceftazidime (CAZ) decreased in 1997, but those have increased in 1998. Inversely, the susceptibility of them against cefotiam (CTM) had been higher in 1997, but those have been lower in 1998. Tobramycin (TOB) showed the most potent activity against P. aeruginosa (both mucoid and nonmucoid strains). All drugs except ampicillin (ABPC) were active against K. pneumoniae. A quite few of K. pneumoniae showed low susceptibilities. Also, we investigated year to year changes in the characteristics of patients, their respiratory infectious diseases, and the etiology. The examination of age distribution indicated that the proportion of patients with ages over 70 years was 48.6% of all the patients showing a slight increase in every year. About the proportion of diagnosed diseases as follows: Bacterial pneumonia was the most frequent with 40.2%. The ratio of it has increased slightly, and the increased rate was 10% in patients with ages over 70 years compared with the results in 1997. Chronic bronchitis have decreased slightly with 27.6% in 1998. Number of strains isolated from patients before administration of antibiotics were more than those after administration of them in chronic bronchitis, but these were almost same number in bacterial pneumonia. Administration of antibiotics has changed the results of the frequency of isolation of bacterial species. Bacterial isolations before administration of antibiotics were as follows: S. pneumoniae 26.7%, H. influenzae 23.8%, S. aureus 13.3% and M. (B.) catarrhalis 10.8%. The frequencies of S. aureus decreased after antibiotics administration over 15 days, but the frequencies of P. aeruginosa (both mucoid and non-mucoid) was not affected. The frequencies of P. aeruginosa was 45.5% after administration over 15 days. The frequencies of S. pneumoniae decreased upon administration of antibiotics, these were only 4.5% over 15 days. The frequencies of H. (

Anti-Bacterial Agents↗
PubMed2000

[Comparison of plasma exchange (PEX) vs. double filtration plasmapheresis (DFPP) with or without steroid administration in a case of MPO-ANCA-positive immune complex type crescentic glomerulonephritis].

The effect of plasmapheresis(PP) monotherapy and PP with corticosteroid administration were evaluated in a male with crescentic glomerulonephritis(CrGN). On the first admission, since he was positive for both anti-neutrophil cytoplasmic myeloperoxydase autoantibody(MPO-ANCA) and circulating immune complex(IC), the treatment was started with PP alone to reduce these autoantibodies immediately. During two months, three series of PP were performed: three sessions of plasma exchange (PEX) with fresh frozen plasma(FFP), two sessions of double filtration plasmapheresis(DFPP), and then, another two sessions of PEX, respectively. ANCA remained suppressed for 4 weeks after the first series of PEX, and increased thereafter. Subsequent DFPP caused a rebound of ANCA titer while the second PEX suppressed ANCA, at least, for 1 week. Though creatinine clearance(Ccr) improved after the first PEX and this level was maintained, ANCA increased again after the second PEX. Therefore the patient was treated with methyl-prednisolone(m-PSL) semipulse therapy followed by mild cocktail therapy including prednisolone(PSL) at 20 mg/day and mizoribine at 100 mg/day. In two weeks, ANCA and IC became negative and Ccr improved further. When PSL was tapered off, the ANCA became positive again. Since ANCA was not suppressed and Ccr declined gradually even after re-administration of oral PSL at 30-40 mg/day, PP was superimposed on steroid therapy with 3 sessions of DFPP and PEX, respectively. Ccr was improved, but ANCA was not sufficiently decreased by DFPP. Subsequent PEX was more efficient than DFPP in reducing the ANCA level. However, m-PSL semipulse was eventually required for complete suppression of ANCA. Thus PP was partially effective, but not sufficient as monotherapy. However it was considered advantageous as an adjunct therapy to reduce the dose of immunosuppressive drugs in CrGN. As to the mode of PP, PEX with FFP appeared to be more effective than DFPP in reducing the plasma ANCA level.

Aged↗
PubMed1999

Transient increases of histamine H1 and H2 receptor mRNA levels in the rat striatum after the chronic administration of methamphetamine.

In our previous studies, we found that behavioral sensitization evoked by repeated administration of methamphetamine (METH) was suppressed by the activation of the histaminergic neuron system in the brain. In continuation of these studies, we measured the levels of H1 and H2 receptor mRNAs in the rat striatum by semi-quantitative reverse transcription-polymerase chain reaction. Seven days after the 21 consecutive administrations of METH (4 mg/kg, i.p.), the levels of both H1 and H2 receptor mRNAs in the rat striatum increased significantly. However, 1 and 14 days after the last administration, there were no significant changes in levels of either H1 or H2 receptor mRNA in the rat striatum. These transient increases of H1 and H2 receptor mRNAs may have some relation to chronic METH abuse and its withdrawal.

Animals↗