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Biomedical subjects

I Inoue

Publications and source records attributed to I Inoue.

At least 91 records · Page 5Linked to original sources
PubMed1997

Synthesis and antitumor activity of quaternary salts of 2-(2'-oxoalkoxy)-9-hydroxyellipticines.

Various kinds of water-soluble quaternary salts of 2-(2'-oxoalkoxy)-9-hydroxyellipticines were synthesized in a search for compounds with potent antitumor activity and low toxicity. Some compounds exhibited more potent antitumor activities than elliptinium (1) and SUN 4599 (3). In particular, 2-(3'-methoxy-2'-oxopropanoxy)-9- hydroxy-5,11-dimethyl-6H-pyrido[4,3-b]carbazolium bromide (4d) showed potent antitumor activities against P388 leukemia, colon 26, and Lewis lung carcinoma.

Animals↗
PubMed1997

Effect of lipophilic ions on the intramembrane charge movement and intracellular Ca2+ release in fetal mouse skeletal muscle cells.

The effects of lipophilic ions on the intramembrane charge movement and intracellular calcium transient were studied using freshly dissociated skeletal muscle cells from mice fetuses. The lipophilic cations Rhodamine 6G and tetraphenylphosphonium (TPP) immobilized part of the intramembrane charge movement in a dose-dependent manner, and inhibited both calcium transient and contraction evoked by membrane depolarization. In contrast, the lipophilic anion 1-anilinonaphthalene-8-sulfonic acid (ANS) had no effect on intramembrane charge movement. We suggest that the lipophilic cations block the voltage-sensing mechanism for the excitation-contraction (E-C) coupling mechanism.

Anilino Naphthalenesulfonates↗
PubMed1997

Evidence for association between the class I subset of the insulin gene minisatellite (IDDM2 locus) and IDDM in the Japanese population.

Although the shortest (class I) minisatellite (i.e., variable number of tandem repeats [VNTR]) alleles in the 5' region of the insulin gene are positively associated with IDDM in Caucasians, the majority of Japanese are homozygous for class I alleles. Here, we determined the exact length, in number of repeat units (RUs), of class I alleles in Japanese subjects. The distribution of class I alleles in Japanese was trimodal, with peaks located at 32/33, 41, and 44 RUs. The shortest component (i.e., 1S [25-38 RUs]) alleles were significantly increased in the IDDM group compared with the control group (54 vs. 46%; P = 0.040). The 1S/1S genotype was significantly increased in the IDDM patients (34 vs. 20%; P = 0.005; relative risk 2.1). Furthermore, the transmission disequilibrium test of Japanese families with 1S/1M or 1S/1L heterozygous parents confirmed the association of 1S alleles; 17 alleles of 1S and 6 alleles of 1M (39-41 RUs) or 1L (42-44 RUs) were transmitted to affected offspring (P = 0.022). In addition, we found tight linkage of 1S with allele 9 of the tyrosine hydroxylase gene microsatellite and allele (-) of the IGF-II gene Apa I polymorphism, but neither 9 nor (-) alleles were significantly associated with IDDM. The present study suggests that a class I subset may have a role in IDDM susceptibility in Japan. It was revealed that the difference between 1S alleles and 1M or 1L alleles is almost consistently characterized by a sequence variation generated by deletion of two copies of an ACAGGGGTCC CGGGG repeat element, implying that sequence variation of class I alleles may influence disease susceptibility.

Adolescent↗
PubMed1996

Impaired locomotor activity and exploratory behavior in mice lacking histamine H1 receptors.

From pharmacological studies using histamine antagonists and agonists, it has been demonstrated that histamine modulates many physiological functions of the hypothalamus, such as arousal state, locomotor activity, feeding, and drinking. Three kinds of receptors (H1, H2, and H3) mediate these actions. To define the contribution of the histamine H1 receptors (H1R) to behavior, mutant mice lacking the H1R were generated by homologous recombination. In brains of homozygous mutant mice, no specific binding of [3H]pyrilamine was seen. [3H]Doxepin has two saturable binding sites with higher and lower affinities in brains of wild-type mice, but H1R-deficient mice showed only the weak labeling of [3H]doxepin that corresponds to lower-affinity binding sites. Mutant mice develop normally, but absence of H1R significantly increased the ratio of ambulation during the light period to the total ambulation for 24 hr in an accustomed environment. In addition, mutant mice significantly reduced exploratory behavior of ambulation and rearings in a new environment. These results indicate that through H1R, histamine is involved in circadian rhythm of locomotor activity and exploratory behavior as a neurotransmitter.

Animals↗
PubMed1996

Cloning, RNA expression, and chromosomal location of a mouse histamine H2 receptor gene.

A mouse histamine H2 receptor (H2R) gene was isolated from a mouse ES cell genomic DNA library. The gene encoded a 358-amino-acid protein and displayed a 95% homology with the rat histamine H2 receptor at the amino acid level. It had features characteristic of other G-protein-coupled receptors. Reverse transcriptase-polymerase chain reaction analysis of total RNA prepared from mouse tissues showed that the gene was highly expressed in stomach and moderately in brain and heart. A weak expression was also detected in liver. An interspecific backcross analysis revealed that the mouse H2R gene, designated Hrh2, was located in the central region of chromosome 13.

Amino Acid Sequence↗
PubMed1996

Characteristics of the mouse genomic histamine H1 receptor gene.

We report here the molecular cloning of a mouse histamine H1 receptor gene. The protein deduced from the nucleotide sequence is composed of 488 amino acid residues with characteristic properties of GTP binding protein-coupled receptors. Our results suggest that the mouse histamine H1 receptor gene is a single locus, and no related sequences were detected. Interspecific backcross analysis indicated that the mouse histamine H1 receptor gene (Hrh1) is located in the central region of mouse Chromosome 6 linked to microphthalmia (Mitfmi), ras-related fibrosarcoma oncogene 1 (Raf1), and ret proto-oncogene (Ret) in a region of homology with human chromosome 3p.

Amino Acid Sequence↗
PubMed1996

Lipoprotein lipase binds to low density lipoprotein receptors and induces receptor-mediated catabolism of very low density lipoproteins in vitro.

Lipoprotein lipase (LPL), the major enzyme responsible for the hydrolysis of plasma triglycerides, promotes binding and catabolism of triglyceride-rich lipoproteins by various cultured cells. Recent studies demonstrate that LPL binds to three members of the low density lipoprotein (LDL) receptor family, including the LDL receptor-related protein (LRP), GP330/LRP-2, and very low density lipoprotein (VLDL) receptors and induces receptor-mediated lipoprotein catabolism. We show here that LDL receptors also bind LPL and mediate LPL-dependent catabolism of large VLDL with Sf 100-400. Up-regulation of LDL receptors by lovastatin treatment of normal human foreskin fibroblasts (FSF cells) resulted in an increase in LPL-induced VLDL binding and catabolism to a level that was 10-15-fold greater than in LDL receptor-negative fibroblasts, despite similar LRP activity in both cell lines. This indicates that the contribution of LRP to LPL-dependent degradation of VLDL is small when LDL receptors are maximally up-regulated. Furthermore studies in LRP-deficient murine embryonic fibroblasts showed that the level of LPL-dependent degradation of VLDL was similar to that in normal murine embryonic fibroblasts. LPL also promoted the internalization of protein-free triglyceride emulsions; lovastatin-treatment resulted in 2-fold higher uptake in FSF cells, indicating that LPL itself could bind to LDL receptors. However, the lower induction of emulsion catabolism as compared with native VLDL suggests that LPL-induced catabolism via LDL receptors is only partially dependent on receptor binding by LPL and instead is primarily due to activation of apolipoproteins such as apoE. A fusion protein between glutathione S-transferase and the catalytically inactive carboxyl-terminal domain of LPL (GST-LPLC) also induced binding and catabolism of VLDL. However GST-LPLC was not as active as native LPL, indicating that lipolysis is required for a maximal LPL effect. Mutations of critical tryptophan residues in GST-LPLC that abolished binding to VLDL converted the protein to an inhibitor of lipoprotein binding to LDL receptors. In solid-phase assays using immobilized receptors, LDL receptors bound to LPL in a dose-dependent manner. Both LPL and GST-LPLC promoted binding of VLDL to LDL receptor-coated wells. These results indicate that LPL binds to LDL receptors and suggest that the carboxyl-terminal domain of LPL contributes to this interaction.

Alanine↗
PubMed1996

A higher proinsulin response to glucose loading predicts deteriorating fasting plasma glucose and worsening to diabetes in subjects with impaired glucose tolerance.

To evaluate the clinical significance of proinsulin determination, we measured glucose, insulin, C-peptide and proinsulin during 75-g oral glucose loading in 59 patients. In a 2.5-year follow-up study of 37 subjects with impaired glucose tolerance (IGT) at the initial test, 11 patients changed from IGT to a normal state and 5 patients showed worsening to overt Type 2 diabetes with elevation of fasting plasma glucose; 21 patients remained unchanged. Although our data showed that both fasting (IGT: p = 0.4523) and 120-min plasma glucose (IGT: p = 0.8168) values at the initial test were not significantly correlated with increased fasting plasma glucose levels in a 2.5-year follow-up study, subjects with a higher 120-min proinsulin response to glucose during the initial OGTT showed a significant correlation (IGT: p < 0.0001) with increased fasting plasma glucose levels after follow-up period and developed Type 2 diabetes. The present findings suggest that the proinsulin response to glucose loading might be a useful indicator for predicting worsening to diabetes in subjects with impaired glucose tolerance.

Administration, Oral↗
PubMed1996

Different effects of azole-antifungal agents on the regulation of intracellular calcium concentration of Trichophyton rubrum.

Prior studies have indicated that intracellular calcium concentration ([Ca2+]i) is involved in fungal cell growth. However, it has not been known whether antifungal drugs affect signal transduction via calcium in fungal cells. In this context, we examined the effects of antifungal drugs, itraconazole, bifonazole and ketoconazole, on [Ca2+]i in Trichophyton rubrum. Itraconazole (1-5 ng/ml) induced a rapid and transient [Ca2+]i increase, peaking at 15-20s in hyphal cells of T. rubrum, but not in spores. The slow descending phase of the [Ca2+]i increase induced by itraconazole was depleted by chelating extracellular calcium with ethylene glycol bis (beta-aminoethyl ether)-N, N,N',N'-tetraacetic acid (EGTA), suggesting that the increase in [Ca2+]i is biphasic: Ca2+ mobilization from the internal pool and influx from the outside of the cell. At 10 ng/ml and 100 ng/ml, however, itraconazole induced an explosive and sustained calcium increase in both spores and hyphae. At less than 1 ng/ml, no [Ca2+]i increase was caused in both hyphae and spores. On the other hand, although some hyphal cells showed a transient [Ca2+]i increase, most of the cells did not show any changes of [Ca2+]i after the addition of ketoconazole at 10 ng/ml. Both spores and hyphal cells incubated with 100 ng/ml of bifonazole or ketoconazole showed a gradual increase of intracellular calcium concentration until 5 min, when the measurement was ceased. These findings suggest that signal transduction via calcium might be involved in some biological effects of itraconazole on T. rubrum, and that bifonazole and ketoconazole could differently affect [Ca2+]i in T. rubrum from itraconazole. In addition, the determination of [Ca2+]i changes induced by antifungal agents may contribute to clarification of the biological effects on fungal membranes.

Antifungal Agents↗
PubMed1996

Inhibitory effects of selenium, vitamin A and butylated hydroxytoluene on growth of human maxillary cancer cells in vitro.

The effects of vitamin A, selenium, and butylated hydroxytoluene (BHT) on the growth of a human maxillary cancer cell line were examined in monolayer cell cultures. The colony-forming assay showed a 50% reduction in the survival rate of the cell line at a concentration of 3.6 micrograms/ml of selenium, 28 micrograms/ml of vitamin A, and 74 micrograms/ml of BHT. Flow cytometric analysis with both FITC-labeled bromodeoxyuridine monoclonal antibody and propidium iodide demonstrated an increase of the S-phase fraction in the presence of selenium, an increase of the G0/G1-phase fraction in the presence of vitamin A, and an increase of the G2-M-phase fraction 1 day followed by an increase of G0/G1-phase fraction from the 3rd to 7th day when BHT was added. These results suggest that the mechanisms of inhibition of DNA synthesis by these compounds are different.

Antibodies, Monoclonal↗
PubMed1996

Expression of p34cdc2 protein kinase and p53 in supraglottic carcinomas.

The clinicopathological significance of the simultaneous expression of the p34cdc2 protein kinase oncogene product and mutant-type p53 oncogene product was studied in 15 supraglottic squamous cell carcinomas. Clinical and histopathological data were recorded from the medical records, and immunohistochemical and DNA cytofluorometric analysis were performed. p34cdc2 was positive in 80% and mutant-type p53 in 53% of the tumors. Their simultaneous expression was seen in 33% of the tumors, but the probability was not statistically significant. Correlations between the expression of p34cdc2 or mutant-type p53 and T, N categories, histological differentiation, and DNA ploidy pattern were not significant. However, when the percentages of p34cdc2 and mutant-type p53-positive cells in the tumor were high, aneuploidy tended to be present and the clinical stage more advanced. It is suggested that the growth and progression of supraglottic carcinomas are associated with the disruption of the regulatory system of the cell cycle.

Aged↗
PubMed1996

Isolation of Bartonella henselae from domestic cats in Japan.

During the period from January to March 1995, the authors first isolated Bartonella henselae from the blood of three (9.1%) of 33 domestic cats in Japan. The three cats were a 1.5-year male pet cat-old with urinary retention, and 6-year-old female pound and age-unknown female pet cats with no abnormalities. The blood was taken in a lysis-centrifugation tube (Wampole Isolator tube) and cultured on 5% rabbit-blood heart infusion agar plates at 35 degrees C in the 5% CO2 atmosphere. Visible tiny rough colonies developed 14 days after incubation. The isolates showed Gram-negative and pleomorphic rods in microscopic observation. The DNA extracted from the isolates was amplified by PCR using two primers, which were specific for the rikettsial citrate synthase gene. The isolates were identified as B. henselae from the patterns of digestion with TaqI and HhaI of the amplified gene. It was confirmed that cats in Japan harbored B. henselae in their blood, and that cats play a significant role as the reservoir of the organism.

Animals↗
PubMed1996

LDL apheresis reduces the susceptibility of LDL to in vitro oxidation in a diabetic patient with hemodialysis treatment.

OBJECTIVE: We studied whether LDL apheresis would alter the susceptibility of LDL to in vitro oxidative modification induced by copper ion in a diabetic patient undergoing hemodialysis treatment. RESEARCH DESIGN AND METHODS: Isolated LDL was dialyzed against phosphate-buffered saline and resuspended at a concentration of 0.3 mg cholesterol mass/ml buffer LDL oxidation was then initiated by addition of 1.66 mumol/l CuSO4, and the formation of conjugated dienes was continuously monitored spectrophotometrically at 234 nm. RESULTS: The duration of the lag phase of LDL obtained after LDL apheresis was markedly longer than that of LDL obtained before LDL apheresis. The propagation rate and the maximum conjugated diene formation of LDL oxidation were not changed after LDL apheresis. CONCLUSIONS: A LDL subfraction that was susceptible to oxidation was removed by LDL apheresis, resulting in reduction of susceptibility of LDL to in vitro oxidation remaining in plasma. LDL apheresis may be of clinical importance for preventing atherosclerotic disease in diabetic patients undergoing hemodialysis.

Aged↗
PubMed1996

Lack of linkage between the endothelial nitric oxide synthase gene and hypertension.

Nitric oxide is an important vasodilator formed in many tissues, including the vascular endothelium. Because of the relationship between nitric oxide and basal vascular tone, genes regulating nitric oxide have been suggested as candidate genes involved with the development of hypertension. At least three isoforms of nitric oxide synthase have been identified. Two of the isoforms, endothelial and inducible nitric oxide synthase, may have particular importance in hypertension. The gene coding for endothelial nitric oxide synthase on chromosome 7 has been cloned. Polymorphic dinucleotide repeats within this nitric oxide synthase gene were used to test for linkage to hypertension in 259 hypertensive siblings from 112 Utah hypertensive sibships. The resulting 194 sibpairs shared 108 alleles identical by state compared to the expected 108.1 alleles shared as estimated from CEPH allele frequencies. After weighting for different sibship sizes, there was only a 3.9% excess allele sharing (P = 0.21). Allele sharing in more severe hypertensive sibpairs (either two antihypertensive medications or an unmedicated diastolic blood pressure (BP) of 100 mm Hg or higher) showed a 6% excess over expected sharing of alleles (P = 0.28). There was no difference between male and female sibpair sharing of alleles (5.2% vs 7.8%, respectively, both not significant). Therefore, there was no evidence that the gene for endothelial nitric oxide synthase was linked to hypertension in these sibpairs.

Adult↗
PubMed1996

[Ganglioneuroma].

Explore the source record for details and available documents.

Adolescent↗
PubMed1995

Characterization of a specific monoclonal antibody 9F5-3a and the development of assay system for oxidized HDL.

We obtained a monoclonal antibody 9F5-3a against oxidative low-density lipoprotein (LDL) modified with CuSO4 and established a sandwich ELISA for detection of oxidized high-density lipoprotein (oxHDL). The 9F5-3a was reacted strongly with oxHDL and to a lesser degree with oxLDL and LDL. In contrast, little or no reactivity was found with HDL. When the generation of oxHDL was limited by the addition of alpha-tocopherol and catalase, reactivity to 9F5-3a was reduced. Incubation of oxHDL with excess lyso-phosphatidylcholine (lyso-PC) also reduced immunoreactivity, but not by only lyso-PC. These results suggested that the epitope is possibly associated with oxHDL-linked lyso-PC induced mainly by the hydroxyl radical.

Animals↗