Biomedical subjects

A Okamoto

Publications and source records attributed to A Okamoto.

At least 91 records · Page 5Linked to original sources

PubMed1999

5-Hydroxy-4-oxo-L-norvaline depletes intracellular glutathione: a new modulator of drug resistance.

To search for compounds that reverse the drug resistance induced by glutathione (GSH), an original screening system to detect intracellular GSH depleters was established. Among 8843 microbes derived from the soil samples tested, the extracts of two Streptomyces species named KS6701 and KS8846, lowered the intracellular GSH level of Saccharomyces cerevisiae 5 x 47. From both the microbes, 5-hydroxy-4-oxo-L-norvaline (HON) was isolated as the active compound. At a concentration of 50-100 micrograms/ml, HON also decreased the GSH/protein level of the human ovarian tumor cell line, 2008/C13*5.25 and reversed its resistance to cisplatin. We also investigated the mechanism of the depletion. HON had little effect on gamma-glutamylcysteine synthetase (gamma-GCS) or glutathione synthetase, but HON decreased the quantity of thiol substances when it was spontaneously reacted with them. This suggested that the GSH depletion by HON occurred through a mechanism different from that of buthionine sulfoximine, a selective gamma-GCS inhibitor.

Aminolevulinic Acid↗

PubMed1998

Crystal structures of Paracoccus denitrificans aromatic amino acid aminotransferase: a substrate recognition site constructed by rearrangement of hydrogen bond network.

Aminotransferase reversibly catalyzes the transamination reaction by a ping-pong bi-bi mechanism with pyridoxal 5'-phosphate (PLP) as a cofactor. Various kinds of aminotransferases developing into catalysts for particular substrates have been reported. Among the aminotransferases, aromatic amino acid aminotransferase (EC 2.6.1. 57) catalyzes the transamination reaction with both acidic substrates and aromatic substrates. To elucidate the multiple substrate recognition mechanism, we determined the crystal structures of aromatic amino acid aminotransferase from Paracoccus denitrificans (pdAroAT): unliganded pdAroAT, pdAroAT in a complex with maleate as an acidic substrate analog, and pdAroAT in a complex with 3-phenylpropionate as an aromatic substrate analog at 2.33 A, 2. 50 A and 2.30 A resolution, respectively. The pdAroAT molecule is a homo-dimer. Each subunit has 394 amino acids and one PLP and is divided into small and large domains. The overall structure of pdAroAT is essentially identical to that of aspartate aminotransferase (AspAT) which catalyzes the transamination reaction with only an acidic amino acid. On binding the acidic substrate analog, arginine 292 and 386 form end-on salt bridges with carboxylates of the analog. Furthermore, binding of the substrate induces the domain movement to close the active site. The recognition mechanism for the acidic substrate analog in pdAroAT is identical to that observed in AspAT. Binding of the aromatic substrate analog causes reorientation of the side-chain of the residues, lysine 16, asparagine 142, arginine 292* and serine 296*, and changes in the position of water molecules in the active site to form a new hydrogen bond network in contrast to the active site structure of pdAroAT in the complex with an acidic substrate analog. Consequently, the rearrangement of the hydrogen bond network can form recognition sites for both acidic and aromatic side-chains of the substrate without a conformational change in the backbone structure in pdAroAT.

Bacterial Proteins↗

PubMed1998

Adult female twins' recall of childhood social class and father's education: a validation study for public health research.

To assess recall of childhood socioeconomic position for public health research, the authors conducted a cross-sectional study of 352 adult women twin pairs enrolled in Examination II of the Kaiser Permanente Women Twins Study carried out in 1989-1990 in Oakland, California. Among twin pairs, 91% (95% confidence interval (CI) 89-94%) agreed on their father's educational level and 81% (95% CI 77-85%) on their childhood social class. Recall did not differ by adult socioeconomic position, zygosity, race/ethnicity, or age. Thus, epidemiologic studies can validly use retrospective data on childhood socioeconomic position to study its relation to adult health status.

Adolescent↗

PubMed1998

Aromatic L-amino acid decarboxylase: conformational change in the flexible region around Arg334 is required during the transaldimination process.

Aromatic L-amino acid decarboxylase (AADC) catalytic mechanism has been proposed to proceed through two consecutive intermediates (i.e., Michaelis complex and the external aldimine). Limited proteolysis of AADC that preferentially digested at the C-terminal side of Arg334 was slightly retarded in the presence of dihydroxyphenyl acetate that formed a stable Michaelis complex. On the contrary, AADC was scarcely digested in the presence of L-dopa methyl ester that formed a stable external aldimine. Similar protection by the substrate analogs was observed in the chemical modification experiment. From these results, we concluded that the region around Arg334 must be exposed and flexible in the unliganded state, and forming the Michaelis complex generated a subtle conformational change, then underwent marked conformational change during the subsequent transaldimination process prerequisite to forming the external aldimine. For further analyses, we constructed a mutant gene encoding in tandem the two peptides of AADC cleaved at the Asn327-Met328 bond inside the putative flexible region. The gene product, fragmentary AADC, was still active with L-dopa as substrate, but its k(cat) value was decreased 57-fold, and the Km value was increased 9-fold compared with those of the wild-type AADC. The absorption spectra of the fragmentary AADC in the presence of L-dopa methyl ester showed shift in the equilibrium of the transaldimination from the external aldimine to the Michaelis complex. Tryptic digestion of the fragmentary AADC removed seven amino acid residues, Met328-Arg334, and resulted in complete inactivation. Susceptibility of the fragmentary enzyme to trypsin was not changed by L-dopa methyl ester revealing the loss of appropriate conformational change in the flexible region induced by substrate binding. From these results we propose that the conformational change in the flexible region is required during the transaldimination process.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1998

Characteristics of pancreatic carcinoma in the elderly.

CONCLUSION: Lymphogenous as well as hematogenous metastases were significantly less frequent in the elderly group of patients, although local invasion was comparable. Survival was comparable between both groups although palliative therapy alone was significantly more frequent in the elderly. BACKGROUND: The relative and absolute numbers of elderly patients continue to increase, as does the incidence of pancreatic carcinoma. To determine the optimal therapy for elderly patients with pancreatic carcinoma, we examined their clinicopathological features. METHODS: The clinical and histopathological features of pancreatic carcinoma in patients 70 yr of age or older (n = 89) were compared with those in patients aged 69 yr or less (n = 184). RESULTS: A total of 273 patients showed histologically tubular adenocarcinomas and their major variants. The male:female ratio peaked at 1:0.3 in patients under 49 yr old but gradually decreased to 1:1.2 in those aged over 80 yr. There were no significant differences between the two groups in the resectability, prognosis, location, or histology of the tumor. Hematogenous and lymphogenous metastases were detected at autopsy in 68 and 61% of patients old than 70, and in 82 and 80% of the younger group.

Adenocarcinoma↗

PubMed1998

Effects of various protease inhibitors on the stability and permeability of [D-Ala2,D-Leu5]enkephalin in the rat intestine: comparison with leucine enkephalin.

The effects of various protease inhibitors on the stability of leucine enkephalin (Leu-Enk) and [D-Ala2,D-Leu5] enkephalin (DADLE) were investigated, and the permeability of these peptides was also examined in an in vitro Ussing chamber. Captopril, thiorphan, bacitracin, bestatin, puromycin, amastatin, and sodium glycocholate (Na-GC) were chosen as protease inhibitors. Regional differences in the stability of Leu-Enk and DADLE were observed, and the rank order of the stability of these peptides was colon > duodenum > ileum > jejunum. Na-GC, amastatin, and puromycin were effective protease inhibitors for improving the stability of these peptides, although captopril and thiorphan did not improve the stability of Leu-Enk. In the transport studies, Leu-Enk did not cross the intestinal membrane in the absence of protease inhibitors, but its transport was improved in the presence of Na-GC. In addition, Na-GC, amastatin, and puromycin improved the permeability of DADLE in both jejunum and colon, while the permeability of DADLE was not improved by the addition of captopril, thiorphan, and bestatin. Furthermore, the permeability of 6-carboxyfluorescein, a poorly absorbable and stable compound, was also improved in the presence of Na-GC and bacitracin at a concentration of 10 mM. These findings indicated that amastatin, puromycin, and Na-GC at a concentration of 0.5 mM might increase the permeability of DADLE due to the improved stability of DADLE in the donor site. However, Na-GC and bacitracin at a concentration of 10 mM had absorption-enhancing activities which might be also related to the enhanced permeability of DADLE across the intestinal membrane.

Animals↗

PubMed1998

Component release from light-activated glass ionomer and compomer cements.

The purpose of this study was to identify and quantify any component released from seven commercially available light-cured or resin-modified glass ionomer and compomer cements. Twenty-one separate cylindrical stainless steel moulds 6 mm in diameter and 1.0 mm deep were filled with one of seven glass ionomer or compomer cements, light activated and then immediately immersed in separate containers of distilled water. Water samples were retrieved over a time period of up to 30 days and retained for analysis. An occlusal cavity 6 mm in diameter was prepared in extracted human third molar teeth with a remaining dentin thickness of 1.6-2.0 mm. A polypropylene chamber was attached to the cemento-enamel junction of each tooth to contain 1 mL of distilled water. Ten teeth were each filled with one of three cements and light activated. Water samples (eluates) were retrieved over a period of time. All samples were analysed by high performance liquid chromatography. Only one component, hydroxyethyl methacrylate (HEMA), was detected in the eluates from both tooth and mould samples. Analysis of diffusion of the HEMA through dentin showed a relatively sustained movement into the pulp space during the first day, with exponential decline thereafter. Our data show that HEMA was released from all of the light activated glass ionomer cements studied and from the compomer, both directly into water and through dentin. This release may be relevant both to the risk of adverse pulpal responses in patients and to the risk of allergy in patients and dental personnel.

Chromatography, High Pressure Liquid↗

PubMed1998

CMDME (curved mesh diagram of mandibular excursion) method for visualization and diagnosis of mandibular movement.

The CMDME (curved mesh diagram of mandibular excursion) method was developed for easy visualization and diagnosis of mandibular movement. This method uses measured mandibular movement to produce a diagram of the range, shape, and inclination of mandibular excursion in three dimensions using any arbitrary landmark of the mandible. First, the mandibular movement of a subject was measured by an opto-electronic movement analysis system capable of measuring mandibular movement with six degrees-of-freedom at a sampling frequency of 100 Hz. For the measurement, the subject was initially instructed to perform four repetitions of mandibular excursion at will, with tooth contact, each lasting 30 s. A total of 12 000 positions of the mandible were thus obtained. Secondly, an attempt was made to match these positions to intersection points (0.1 mm apart) of a CMDME (i.e. mesh) for arbitrary mandibular landmarks with intercuspal position at the origin. The CMDME method can visualize mandibular excursion, and can be used to compare several landmarks, different subjects, or different times. This makes this method an effective diagnostic tool for mandibular movement.

Adult↗

PubMed1998

Patency of the accessory pancreatic duct in relation to its course and shape: a dye-injection endoscopic retrograde pancreatography study.

OBJECTIVE: The accessory pancreatic duct (APD) exhibits several appearances on pancreatography. We examined the patency of the APD by dye-injection endoscopic retrograde pancreatography (ERP), and studied the relationship between patency and duct course and shape. METHODS: There were 213 patients with satisfactory imaging of the entire normal APD who also underwent dye-injection ERP. The length and maximum diameter of the APD and the length of the main pancreatic duct (MPD) from its orifice to the junction with the APD were measured. RESULTS: The caliber of the patent APD was 1.6 +/- 0.6 mm. This was significantly larger than the caliber (1.1 +/- 0.4 mm) of the nonpatent APD (p < 0.01). The length of the MPD from its orifice to the junction with the patent APD was 32.7 +/- 12.5 mm. This was significantly longer than the length to the junction with the nonpatent APD (22.5 +/- 8.1 mm) (p < 0.01). The APD was classified according to duct course: long type, intermediate type, short type, or ansa type. Patency was most common in the long type APD (74.5%). The terminal shape of the APD was also used to classify the ducts: stick type, branch type, saccular type, cudgel type, or spindle type. Patency was most frequently observed in the spindle and cudgel type ducts. CONCLUSIONS: Patency of the APD might be dependent on duct caliber, course, and terminal shape of the duct.

Cholangiopancreatography, Endoscopic Retrograde↗

PubMed1998

[An evaluation of efficacy of minocycline as an anti-rheumatic drug in patients with active and refractory rheumatoid arthritis].

The efficacy and safety of minocycline was investigated in Japanese patients with rheumatoid arthritis (RA) who had already received more than three disease modifying anti-rheumatic drugs (DMARDs). Minocycline was administered at 100 mg twice a day to fifteen patients with active RA. The drug efficacy was evaluated by the clinical variables including the number of painful and/or swollen joints, the duration of morning stiffness, grip strength, the erythrocyte sedimentation rate, serum concentrations of C-reactive protein, and the titer of rheumatoid factor. Three patients experienced adverse effects such as dizziness and abdominal pain or discomfort, but only one patient with abdominal pain and dizziness was discontinued. Fourteen RA patients, who had taken minocycline for at least 6 months, were subjected to the clinical evaluation. Among them, 8 patients (54%) showed a significant improvement of clinical valuables for disease activity, beginning even at 4 weeks of the therapy. The continued effects were observed in 8 patients with over 1 year-minocycline therapy. Intriguingly, an active patient with a history of multiple DMARDs-resistancy showed a marked favorable response to this drug. The present study indicates that minocycline may be an effective DMARD with highly safe performance for patients with active and refractory RA. This is the first demonstration of the benefit of minocycline in the Japanese patients.

Aged↗

PubMed1998

Calcified pseudoaneurysm of the left ventricle.

Left ventricular pseudoaneurysm following acute myocardial infarction generally has an extremely poor prognosis without surgical repair. A rare case of long term survival for 23 years following cardiac rupture with subsequent development of a left ventricular pseudoaneurysm after acute myocardial infarction is reported. The patient suffered acute inferoposterior myocardial infarction in July 1974 at the age of 58 years. Clinical course and findings obtained on reassessment in 1992 (transesophageal echocardiography, chest computed tomography and left ventriculography) confirmed a left ventricular pseudoaneurysm. The patient refused surgical resection of the lesion, but remained alive and well in 1997 (81 years old). In this case, it is considered that containment of hemorrhage by pericardial adhesion prevented immediate tamponade and sudden death.

Aged↗

PubMed1998

[Comprehensive medicine and 17-KS-S].

In order to evaluate QOL from the perspective of comprehensive medicine, a self-rated QOL Questionnaire and urine 17-KS-S (abbreviated S), 17-OHCS (OH), S/OH were examined in 268 patients (including 11 terminally ill cancer patients) and 31 nurses. Lower S and S/OH were observed in both groups, but OH was higher in patients' group and lower in the nurses' group. Total QOL score was lower in patients' group, but higher in nurses' group. The correlation of each parameter, S, OH and S/OH was related to QOL items. Among terminally ill cancer patients, supplementary treatments were performed. During the course, the elevation of S were observed. In conclusion, S, OH and S/OH were related to QOL and they were considered an objective method of evaluating QOL.

17-Hydroxycorticosteroids↗

PubMed1997

A nucleotide polymorphism in ERCC1 in human ovarian cancer cell lines and tumor tissues.

We studied the DNA sequence of the entire coding region of ERCC1 gene, in five cell lines established from human ovarian cancer (A2780, A2780/CP70, MCAS, OVCAR-3, SK-OV-3), 29 human ovarian cancer tumor tissue specimens, one human T-lymphocyte cell line (H9), and non-malignant human ovary tissue (NHO). Samples were assayed by PCR-SSCP and DNA sequence analyses. A silent mutation at codon 118 (site for restriction endonuclease MaeII) in exon 4 of the gene was detected in MCAS, OVCAR-3 and SK-OV-3 cells, and NHO. This mutation was a C-->T transition, that codes for the same amino acid: asparagine. This transition converts a common codon usage (AAC) to an infrequent codon usage (AAT), whereas frequency of use is reduced two-fold. This base change was associated with a detectable band shift on SSCP analysis. For the 29 ovarian cancer specimens, the same base change was observed in 15 tumor samples and was associated with the same band shift in exon 4. Cells and tumor tissue specimens that did not contain the C-->T transition, did not show the band shift in exon 4. Our data suggest that this alteration at codon 118 within the ERCC1 gene, may exist in platinum-sensitive and platinum-resistant ovarian cancer tissues.

Antineoplastic Agents↗

PubMed1997

Paracoccus denitrificans aromatic amino acid aminotransferase: a model enzyme for the study of dual substrate recognition mechanism.

The gene for aromatic amino acid aminotransferase (ArAT) from Paracoccus denitrificans was cloned, sequenced, and overexpressed in Escherichia coli cells. The sequence differed from that reported previously [Takagi, T., Taniguchi, T., Yamamoto, Y., and Shibatani, T. (1991) Biotechnol. Appl. Biochem. 13, 112-119]. The enzyme (pdArAT) was purified to homogeneity, and characterized. It was similar to aspartate aminotransferase (AspAT) and ArAT of E. coli (ecArAT) in many respects, including gross protein structure and spectroscopic properties. pdArAT showed activities toward both dicarboxylic and aromatic substrates, and analysis of the binding of substrate analogs and quasisubstrates to the enzyme showed that both dicarboxylic and aromatic substrates take a similar orientation in the active site of pdArAT; these properties are essentially identical with those of ecArAT. As in the case of ecArAT, neutral amino acids with larger side chains are better substrates for pdArAT, suggesting that hydrophobic interaction between the substrate and the enzyme is important for the recognition of substrates with neutral side chains. pdArAT catalyzed transamination of phenylalanine and tyrosine far more efficiently (10(2)-fold in terms of kcat/Km) than those of straight-chain aliphatic amino acids with similar side-chain surface area, whereas ecArAT did not show significant preference for aromatic amino acids over aliphatic amino acids. This shows that the substrate-side-chain-binding pocket of pdArAT, as compared with the pocket of ecArAT, is well suited in shape for interaction with the phenyl and hydroxyphenyl rings of substrates. Thus, pdArAT is an ideal enzyme among ArATs for the study of the high-specificity recognition of two different kinds of substrates, the one having a carboxylic side chain and the other having an aromatic side chain.

Amino Acid Sequence↗

PubMed1997

Polyamine content of ordinary foodstuffs and various fermented foods.

Soybeans, tea leaves, and mushrooms were conspicuously rich in spermidine, while oranges contained a large amount of putrescine. Among the fermented foods, soy sauces were rich in putrescine and histamine, while Japanese sake contained plenty of agmatine. These polyamines are thought to be produced from amino acids during fermentation with amino acid decarboxylases formed by the micro-organisms.

Alcoholic Beverages↗

PubMed1997

High efficiency transformation of Bacillus brevis by electroporation.

Various conditions in the Bacillus brevis transformation by electroporation were investigated to increase the efficiency. Competent cell volume and presence of polyethylene glycol 6000 and single stranded DNA on pulsing were critical for the efficiency. As a result, we established the improved method by which 10(7)-10(8) transformants/microgram plasmid DNA could be obtained.

Bacillus↗

PubMed1997

Alveolar bone loss in rats infected with a strain of Prevotella intermedia and Fusobacterium nucleatum isolated from a child with prepubertal periodontitis.

Prevotella intermedia and fusobacterium nucleatum are associated with various forms of periodontal disease. The purpose of the present study was to infect the clinical isolates of these periodontopathic bacteria and to induce a significant loss of alveolar bone in specific pathogen-free (SPF) rats in the absence of ligatures. P. intermedia YKD8 and F. nucleatum YKZ5 were isolated from a prepubertal periodontitis patient, while P. gingivalis MWB13 was from a patient with juvenile periodontitis. At first, SPF Sprague-Dawley rats (70 days of age, male) were infected with A. viscosus Ny1R and subsequently superinfected with P. gingivalis MWB13, P. intermedia YKD8, or F. nucleatum YKZ5, respectively. The control group was infected with A. viscosus Ny1R alone. All rats were killed and periodontal bone levels were assessed morphometrically 135 days after the first infection with A. viscosus. P. intermedia YKD8 was recovered frequently from rats, with serum antibody levels remaining highly elevated throughout the experiment. Significant loss of alveolar bone was found in rats infected with P. intermedia YKD8, the virulence of which was equivalent to that of P. gingivalis MWB13. F. nucleatum YKZ5 also induced alveolar bone loss, but not significantly when compared with rats infected with A. viscosus Ny1R alone.

Aggregatibacter actinomycetemcomitans↗

PubMed1997

Hepatic arterial infusion chemotherapy combined with hyperthermia for metastatic liver tumors of colorectal cancer.

The efficacy of combined hepatic arterial infusion chemotherapy and hyperthermia for unresectable hepatic tumors of colorectal cancer was retrospectively compared with hepatic arterial infusion chemotherapy alone. Nine cases were treated with combination therapy and eight cases were treated with hepatic arterial infusion alone. The response rate in the combined hepatic arterial infusion/hyperthermia group was higher (44% v 25%) and the survival period longer (2-year survival, 35% v 12%) than in the group treated with hepatic arterial infusion alone. The toxicity was not severe, with the exception of gastrointestinal symptoms, suggesting that this combination of modalities is useful in the treatment of metastatic liver tumors.

Aged↗