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Biomedical subjects

K Iwamoto

Publications and source records attributed to K Iwamoto.

At least 37 records · Page 2Linked to original sources
PubMed2001

A polymorphism in the 5' untranslated region and a Met229-->Leu variant in exon 5 of the human UCP1 gene are associated with susceptibility to type II diabetes mellitus.

AIMS/HYPOTHESIS: The cumulative effects of several thrifty factors could contribute to the pathogenesis of Type II (non-insulin-dependent) diabetes mellitus. We screened the human UCP1 gene (UCP1) for polymorphisms associated with susceptibility to Type II diabetes. METHODS: By using PCR and single-strand conformation polymorphism analysis, UCP1 were screened for mutations in 25 Type II diabetic subjects and 25 healthy control subjects. The allele frequencies of the detected polymorphisms were determined by PCR and restriction fragment length polymorphism analysis in 320 diabetic subjects and 250 control subjects. RESULTS: An A-->C transition in the 5' untranslated region (UTR) of exon 1 (112 bp upstream of the translation initiation codon) and a Met229-->Leu variant were detected. The allele frequencies for the C variant and for the Leu229 variant were higher in the Type II diabetic group than in the control group (p = 0.017 and p = 0.038, respectively). These polymorphisms were in linkage disequilibrium (p < 0.00001). Luciferase assay showed that the former variant in the 5' UTR may affect the promoter activity of UCP1. CONCLUSION/INTERPRETATION: Both the A-->C polymorphism and the Met229-->Leu polymorphism of UCP1 are in linkage disequilibrium and could be one of the diabetes associated single nucleotide polymorphisms (SNPs).

5' Untranslated Regions↗
PubMed2001

Purification and Characterization of Mannitol-l-Phosphatase in the Red Alga Caloglossa continua (Ceramiales, Rhodophyta).

Purification of mannitol-l-phosphatase, an enzyme catalyzing the final step of mannitol biosynthesis, was first achieved in the mannitol-accumulating red alga Caloglossa continua (Okamura) King et Puttock. The enzyme was shown to be a monomer, since gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis gave close values of apparent molecular weights of 28,500 and 30,200, respectively. The protein exhibited an isoelectric point of 4.8. The substrate specificity for mannitol-l-phosphate (MIP) was very high, and that for K(m)(MIP) was 0.41 mM. The catalytic activity was optimal at pH 7.4. The enzyme was activated by Mg(2+), but was strongly inhibited by Ca(2+), NaF, N-ethylmaleimide, and p-hydroxymercuribenzoic acid. Seawater levels of NaCl and physiological levels of mannitol also inhibited the activity by 50% or more. Changes in the concentrations of those ions and metabolites may regulate the biosynthesis of mannitol as an osmoregulant in vivo.

Journal Article↗
PubMed2001

Elimination of POR expression correlates with red leaf formation in Amaranthus tricolor.

Amaranthus tricolor L. tricolor cv. Earlysplendor, an ornamental amaranth, generates red leaves instead of green leaves in late summer to early autumn. Red leaf formation was promoted under short-day conditions and delayed by night-break treatments. Red leaves were characterized by lower levels of chlorophyll accumulation rather than higher levels of red pigment (betacyanin) accumulation. However, the metabolic activity toward the production of Mg-protoporphyrin, an intermediate in the biosynthesis pathway for chlorophyll, was detected in red leaves as well as in green leaves. RNA gel blot analysis was performed to assess the expression of nine genes encoding eight enzymes involved in chlorophyll biosynthesis. Among these enzymes, red-leaf-specific reduction of gene expression was observed only for NADPH-protochlorophyllide oxidoreductase (POR), a key enzyme catalyzing a later step of chlorophyll biosynthesis. In addition, immunoblot analysis showed no accumulation of POR protein(s) in red leaves. These data indicate that the repression of POR gene expression and resultant loss of chlorophyll synthesis activity plays a role in red leaf formation of A. tricolor.

Anthocyanins↗
PubMed2001

Effect of oxatomide, an antiallergic agent, on QT interval in dogs.

Oxatomide (CAS 60607-34-3, KW-4354) is an effective antiallergic agent for allergic rhinitis, urticaria, pruritus cutaneous, and eczema/dermatitis, etc. Terfenadine (CAS 50679-08-8) and astemizole (CAS 68844-77-9), antiallergic agents, have been reported to induce QT prolongation leading to serious ventricular arrhythmia (torsades de pointes) as cardiovascular adverse effects. The present study was carried out to determine whether oxatomide and terfenadine have effects on QT interval as a single drug or in combination with itraconazole (CAS 84625-61-6), an antifungal agent with a CYP3A4 inhibitory effect, in conscious dogs. Terfenadine alone induced QT prolongation at the dose of 30 mg/kg p.o. When itraconazole was administered at the dose of 100 mg/kg p.o. 1 h before terfenadine administration, terfenadine induced QT prolongation at the dose of 10 mg/kg p.o. On the other hand, oxatomide did not induce QT prolongation either as a single agent at the dose of 30 mg/kg p.o. or in combination with itraconazole at the dose of 10 mg/kg p.o. The results present no evidence that oxatomide has the potential to provoke ventricular arrhythmia.

Animals↗
PubMed2001

Changes in the dissolution of tolbutamide by a traditional Chinese medicine, Sho-saiko-to (Xiao Chaihu Tang).

Dissolution rate is considered an important factor affecting absorption and efficacy after the oral administration of tolbutamide. Since in many cases traditional Chinese medicines, including Sho-saiko-to (TJ-9, Xiao Chaihu Tang), are taken with other drugs, it is likely that the dissolution and absorption of concomitant drugs in the gastrointestinal tract are influenced by the presence of traditional Chinese medicines. In this study, the effects of TJ-9 on the in vitro dissolution of tolbutamide were examined. We carried out the dissolution test of tolbutamide in the absence or presence of traditional Chinese medicines (Kakkon-to, TJ-1; Hachimi-jio-gan, TJ-7; Chorei-to, TJ-40; Shakuyaku-kanzo-to, TJ-68; TJ-9; Glycyrrhizae Radix, GR; glycyrrhizin, GL) by using a pH 1.2 dissolution medium. Tolbutamide was determined by HPLC assay. The moment parameters, ie., mean dissolution time (MDT), and the dissolution rate constant up to 20 min (kd) were estimated from the dissolution profiles on the basis of the first-order kinetics. Preparations containing GR, namely TJ-1, TJ-9 and TJ-68, significantly reduced the kd and increased the MDT of tolbutamide, while TJ-7 and TJ-40 had no effect on the early dissolution profile of tolbutamide. The extent of decrease in the kd in the presence of TJ-1, TJ-9 and TJ-68 was dependent on their GR contents. Similar inhibitory effects on the dissolution rate of tolbutamide were observed when GR alone was added to the test medium. In addition, GL, a major constituent of GR, induced a 50% increase in MDT and a 30% decrease in kd. The above results indicate that Chinese traditional preparations containing GR have an inhibitory effect on the in vitro dissolution of tolbutamide, which is derived from GL in the preparations.

Algorithms↗
PubMed2001

Effects of sho-saiko-to (xiao chai hu tang), a Chinese traditional medicine, on the gastric function and absorption of tolbutamide in rats.

This study was carried out to investigate the effects of Sho-saiko-to (Xiao Chai Hu Tang), a Chinese traditional medicine, on the gastric function including the gastric emptying rate (GER) and intragastric pH in rats. Additionally, the effects of the GER and intragastric pH on tolbutamide absorption after oral administration were examined. The GER measured at 40 min after dosing was reduced to about 70% by the pretreatment of Sho-saiko-to (500 mg/kg). The plasma tolbutamide concentration in the rats treated with a 250 mg/kg dose of Sho-saiko-to was significantly lower than that in the control group. Plasma tolbutamide concentrations increased along with the GER in the group co-administered Sho-saiko-to, and there were significant correlations between the GERs and plasma levels in both time points at 20 and 40 min after administration. In the study using pylorus-ligated rats, Sho-saiko-to significantly elevated the intragastric pH, but induced no change in the concentrations of tolbutamide dissolved in the gastric content. Additionally, Sho-saiko-to did not change the area under the plasma concentration-time curve (AUC) of tolbutamide up to 60 min after administration into the stomach loop, and gastric absorption has been considered to minimally contribute to whole absorption of tolbutamide in the gastrointestinal tract. These results indicate that Sho-saiko-to has an inhibitory effect on the function of gastric emptying in rats. The reduced gastric emptying could affect gastrointestinal absorption, resulting in the lower plasma concentration of tolbutamide after oral administration. Furthermore, it is suggested that Sho-saiko-to can raise the intragastric pH but affect neither the intragastric dissolution nor the gastric absorption of tolbutamide.

Administration, Oral↗
PubMed2001

[Effect of olopatadine hydrochloride, a novel antiallergic agent, on the QT interval in dogs].

Olopatadine hydrochloride (olopatadine), a novel antiallergic agent, is effective in the treatment of allergic rhinitis, chronic urticaria, eczema and dermatitis. It has been reported that terfenadine and astemizole cause side effects on the circulatory system such as QT prolongation followed by serious ventricular arrhythmias (torsades de pointes). To investigate the possibility of QT prolongation, we used both conscious normal dogs and hypokalemia-anesthetized dogs under two conditions: 1) olopatadine used alone and 2) olopatadine used in combination with itraconazole, the CYP3A4-inhibiting antifungal agent, in the present investigation. The group treated with terfenadine alone (30 mg/kg, p.o.) and the group treated with a combination of terfenadine (10 mg/kg, p.o.) and itraconazole (100 mg/kg, p.o.) had a significantly prolonged QT interval. On the other hand, the group treated with olopatadine alone (30 mg/kg, p.o.) and the group treated with a combination of olopatadine (30 mg/kg, p.o.) and itraconazole (100 mg/kg, p.o.) did not show any significant changes in QT interval. Moreover, olopatadine (1 and 5 mg/kg, i.v.) did not influence the QT interval in hypokalemia-anesthetized dogs. These results suggest that there is very little possibility of QT prolongation as a result of clinically used olopatadine.

Animals↗
PubMed2001

Isolation of chlamydia psittaci from domestic cats with oculonasal discharge in Japan.

Eight strains of Chlamydia psittaci were isolated in Japan from the nasal and conjunctival swabs of six household cats using the L929 cell line of mouse fibroblast origin. The isolates were identified as C. psittaci on the basis of the formation of characteristic inclusion bodies in the cell culture detected by Giemsa stain and immunofluorescence. Comparison of nucleotide sequences of the ompA gene amplified from the three isolates with the published sequence of feline FEPN strain of C. psittaci showed almost 100% homology.

Animals↗
PubMed2000

Genomic organization and alternative transcripts of the human PQBP-1 gene.

PQBP-1 has been identified as a protein that binds to huntingtin, androgen receptor and transcription factor Brain-2 through their homopolymeric glutamine repeats. We here report the genomic organization of the human PQBP-1 gene and its multiple alternative transcripts. The coding region of PQBP-1 comprises six exons and five introns, and four types of alternative transcript, designated PQBP-1a to PQBP-1d, were found in addition to the PQBP-1 transcript reported originally. All of the PQBP-1 transcripts retain the WW domain in the N-terminal region, a potent transactivator domain. On the other hand, there is a wide variation in their C-terminal regions. Importantly, PQBP-1a and PQBP-1d lack the domain responsible for the interaction with homopolymeric glutamine repeats and a nuclear localization signal.

Alternative Splicing↗
PubMed2000

Reaction of o-oxazolinylphenyllithium with carbon monoxide. Carbonylative cyclization via an aroyllithium intermediate

The carbonylation of a phenyllithium containing an oxazoline group at the ortho position, followed by quenching with water, afforded a tricyclic compound, 3,3-dimethyl-2,3-dihydrooxazolo[2, 3-a]isoindol-5(9bH)-one, in 91% yield. This reaction proceeded via an intramolecular cyclization of the aroyllithium species, to give the tricyclic dienolate. Treatment of the tricyclic dienolate with electrophiles, such as alkyl halides, aldehydes, ketones, and epoxides gave the substituted oxazolo[2,3-a]isoindolinones in good yield.

Journal Article↗
PubMed2000

Primary volvulus of the small intestine in an adult, and review of 15 other cases from the Japanese literature.

We report case of primary volvulus of the small intestine and review 15 cases from the Japanese literature. A 56-year-old woman, with a history of appendectomy 30 years previously, was admitted with abdominal distension and signs of peritonitis. Abdominal computed tomography (CT) demonstrated a whirl-like pattern of the mesentery, showing the tightly twisted mesentery around the point of torsion. An emergency laparotomy revealed strangulation of the small intestine, from 200 cm anal to the Treitz ligament to 5 cm oral to the terminal ileum, caused by 360 degrees clockwise torsion. There was no adhesion caused by the previous operation nor were there any congenital anomalies. The strangulated intestine was removed and jejunocolonostomy was performed. The patient was discharged from hospital on day 39 after the operation. Primary volvulus of the small intestine was reported to be rare in Japan, but the mortality was 26%. Immediate diagnosis and surgical intervention is essential to achieve a good outcome. A whirl-like pattern of the mesentery is a typical sign of this condition on CT.

Female↗
PubMed2000

Involvement of angiotensin II and endothelin-1 in the development of submandibular gland hypertrophy in response to isoproterenol in rats.

We investigated whether angiotensin II (Ang II) and endothelin-1(ET-1) are involved in submandibular hypertrophy in response to repeated treatment with isoproterenol (ISO) in rats. The immunoreactive Ang II (IRAng II) and immunoreactive ET-1 (IRET-1) contents of ISO-induced hypertrophy were significantly higher than those of control glands. Treatment of isolated gland tissues with ISO (1 microM) or dobutamine (1 microM) caused significant increases in the IRAng II and IRET- 1 contents of the glands compared with controls. These increases were suppressed by pretreatment with enalapril (3 microM) or captopril (3 microM). Treatment with Ang II (10 microM) also caused an increase in IRET-1 content. Our findings suggest that Ang II and ET-1 are involved in the submandibular gland hypertrophy that develops in rats repeatedly treated with ISO, and that these biologically active peptides may act as growth factors. They also imply that the tissue renin-angiotensin system and Ang II specific receptors are present in the submandibular glands.

Adrenergic beta-Agonists↗
PubMed2000

A temperature study on critical micellization concentration of the novel platelet-activating factor receptor antagonist E5880 in water by electric conductivity measurements.

To clarify the behavior of the novel platelet-activating factor (PAF) receptor antagonist E5880 in aqueous solution, electric conductivity was measured at different temperatures (every 5 degrees C), ranging from 15 degrees C to 50 degrees C. Critical micellization concentration (CMC) of E5880 was dependent on the temperature; at 30 degrees C, the CMC value was smallest (0.143 mM). Below that temperature, the enthalpy for formation of the micelle (delta Hm0) was positive, and the formation of micelles was endothermic; above that temperature, delta Hm0 was negative, and the formation of micelles was exothermic.

Drug Administration Routes↗
PubMed2000

Characterization of the physicochemical properties of the micelles of platelet-activating factor (C18:0).

The purpose of this study was to clarify the physicochemical properties of the micelles of platelet-activating factor (PAF; C18:0). The critical micelle concentration (CMC) of PAF (C18:0) was determined (0.20 microM) using fluorescence techniques. The fluidity and the micropolarity of the PAF (C18:0) micelle were similar to those of the micelle of stearoyl lysophosphatidylcholine.

Anilino Naphthalenesulfonates↗
PubMed2000

Optimization of the formulation and characterization of the physicochemical properties of the novel platelet-activating factor receptor antagonist E5880.

The injectable formulation of E5880, a novel platelet-activating factor (PAF) receptor antagonist, was determined from the study of pH stability, the selection of excipient, and the relationship between moisture and stability. The physicochemical properties of E5880 in the optimized formulation (0.6 mg/ml of E5880, 0.1% [4.8 mM] citric acid, 10% lactose, pH 2.8) were characterized. The critical micelle concentration of E5880 in the buffer was 0.1 mg/ml, and the structure was of spherical micelles. The micellar size was 5.6 nm and did not change before and after lyophilization and storage. The number of the molecules per micelle was 40. The micropolarity around the hydrocarbon region of the micelle was similar to that of butanol.

Chemistry, Pharmaceutical↗
PubMed2000

The effect of divalent cations on the membrane properties and pharmacokinetics in rat of the lipid A analogue E5531.

To obtain information on the effects of Ca2+ on the membrane properties of the lipid A analogue E5531, we have determined the aggregate size, zeta potential, membrane fluidity, micropolarity and permeability of the E5531 membrane as a function of Ca2+ levels. Within the molar ratios of [Ca2+]/[E5531] = 1 and 3, Ca2+ increased the zeta potential of the E5531 membrane but had no effect on aggregate size (approximately 20 nm). Within the above ratios, Ca2+ decreased the membrane fluidity, as measured by micropolarity of E5531 and increased the phase transition temperature. The pharmacokinetics in rats for these samples with different membrane fluidity, prepared by changing the pre-dose formulation concentration of Ca2+, was determined and a correlation between membrane fluidity and pharmacokinetics was clearly observed. It thus appears that Ca2+ effects the membrane fluidity of E5531 as well as its pharmacokinetics in rats.

Animals↗