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Biomedical subjects

K Sakurai

Publications and source records attributed to K Sakurai.

At least 73 records · Page 4Linked to original sources
PubMed2000

Phase separation in the mixture of schizophyllan and poly(ethylene oxide) in aqueous solution driven by a specific interaction between the glucose side chain and poly(ethylene oxide).

We found that the mixture of schizophyllan and poly(ethylene oxide) in aqueous solution underwent phase separation at around 3-4 degrees C, and this temperature was independent of both polymer concentration and the difference in poly(ethylene oxide) molecular weight (Mw 6000 and 70,000). The phase-separation took place at the same temperature at which the optical rotation changed. Since the optical rotation change is ascribed to the difference in the nature of hydrogen bonding between the schizophyllan side chain and water, the phase separation is also considered to be due to an interaction between poly(ethylene oxide) and schizophyllan. The phase-separation temperature increased on changing H2O to D2O in accordance with a change in the optical rotation, confirming the specific interaction essential for the phase separation.

Chemical Phenomena↗
PubMed2000

Mitochondrial permeability transition induced by 1-hydroxyethyl radical.

Impairment of mitochondrial functions has been found in ethanol-induced liver injury. Ethanol can be oxidized to the 1-hydroxyethyl radical (HER) by rat liver microsomal systems. Experiments were carried out to evaluate the ability of HER to cause mitochondrial swelling as an indicator of the mitochondrial permeability transition (MPT). Electron spin resonance (ESR) spectroscopy was used to detect HER and to study its interaction with mitochondria. The ESR signal intensity of the spin adduct formed from alpha-(4-pyridyl-1-oxide) N-tert-butylnitrone (POBN) and HER generated from either a thermic decomposition of 1,1'-dihydroxyazoethane (DHAE) or a Fenton reaction system containing ethanol was markedly diminished by the addition of mitochondria, indicating an interaction between HER and mitochondria. Exposure of rat liver mitochondria to HER generated from either system caused swelling, as reflected by a decrease in absorbance at 540 nm, in a HER concentration-dependent and a cyclosporin A-sensitive manner. Mitochondrial swelling was also induced in the Fenton reaction system without ethanol. The DHAE-dependent generation of HER in mitochondrial suspension resulted in a decrease of membrane protein thiols and collapse of the membrane potential (delta psi). The swelling induced by HER was prevented by glutathione and vitamin E, but not by superoxide dismutase. Catalase did not prevent the swelling caused by the acetaldehyde/hydroxylamine O-sulfonate (HOS) system, but was inhibitory in the Fenton reaction system with or without ethanol. These results indicate that HER, as well as hydroxyl radical, can induce the MPT, and suggest the possibility that the collapse of delta psi caused by HER may, at least in part, contribute to impairment of mitochondrial function caused by ethanol and in ethanol-induced liver injury.

Animals↗
PubMed2000

Prevalence of anorexia nervosa and bulimia nervosa in a geographically defined area in Japan.

OBJECTIVE: Little has been understood regarding the frequency of eating disorders in Japan. This study was designed to identify the prevalence of anorexia nervosa (AN) and bulimia nervosa (BN) in Japan. METHOD: We asked doctors in all of the relevant medical facilities (130 hospitals and 1,326 clinics) in Niigata Prefecture to report patients with DSM-IV-diagnosed eating disorders who appeared or were admitted between 20-24 October 1997. The response rate was 94.4%. RESULTS: The estimated point prevalences of AN and BN were 4.79 and 1.02, respectively, per 100,000 females. Specifically for the age group of 15-29 years, the prevalence of AN was 17.10 and that of BN 5.79. DISCUSSION: The prevalence of AN and BN in Japan is lower than that for European Caucasian populations. This result may be due to cultural and ethnic differences and/or it may be a transient phenomenon.

Adolescent↗
PubMed2000

Isolation and characterisation of adenoid squamous carcinoma cells highly producing SCC antigen and CEA from carcinoma of the maxillary sinus.

A serially transplantable adenoid squamous carcinoma tumour line (SCCMM) derived from carcinoma of the maxillary sinus of a 56-year-old male with high serum levels of SCC antigen (SCC-Ag) and carcinoembryonic antigen (CEA) was established in athymic nude mice. Nude mouse tumours produced by transplantation of operated material showed similar histological features to those of the original tumour and expression of SCC-Ag and CEA immunohistochemically. In addition, SCC-Ag and CEA in sera of tumour-bearing nude mice were detected at high levels in proportion to the relative tumour weight. The primary cultured tumour cells demonstrated the expression of SCC-Ag and CEA and the production of these antigens into culture medium. The serum levels of these tumour antigens were decreased concomitant with tumour regression by antitumour drug administration. Therefore, this tumour line and its cultured cells could provide a useful model for investigation of the relationship between tumour growth and expression of these tumour antigens.

Animals↗
PubMed2000

Rebamipide, an antiulcer drug, prevents DSS-induced colitis formation in rats.

This study was conducted to investigate the efficacy of rebamipide against experimental colitis induced by dextran sulfate sodium (DSS) in a rat model of inflammatory bowel disease. Experimental colitis was induced in male Wistar rats by oral administration of 3% DSS solution for one week. The rats were provided with standard diet containing 0.105% rebamipide (160 mg/kg/day) for 1 week. In rats treated with rebamipide, clinical (body weight loss, bloody diarrhea, reduced physical activity, severe anemia, shortened colonic length, and perianal injury) and histopathological (pathological lesion score) findings of DSS colitis were significantly less than in rats with DSS colitis not treated with rebamipide. Rebamipide thus inhibited the induction of colitis. Rebamipide significantly reduced concentrations of both interleukin-1alpha and GRO/CINC-1 (IL-8-like substance) and cell infiltrates in colonic wall, in parallel with decreased activity of myeloperoxidase. It also reduced expression of IL-1 mRNA but did not influence expression of GRO/CINC-1 mRNA. The attenuation of colonic indices of colitis by rebamipide in this rat model suggests that this drug might have beneficial effects in the treatment of human ulcerative colitis. These effects of rebamipide are attributable to its inhibition of inflammatory cytokine-mediated granulocyte (neutrophil) infiltration into the colon.

Alanine↗
PubMed2000

Pharmacological analysis by HOE642 and KB-R9032 of the role of Na(+)/H(+) exchange in the endothelin-1-induced Ca(2+) signalling in rabbit ventricular myocytes.

The role of Na(+)/H(+) exchange in endothelin-1 (ET-1)-induced increases in Ca(2+) transients and cell shortening was studied in rabbit ventricular myocytes loaded with indo-1/AM. Selective inhibitors of Na(+)/H(+) exchange HOE642 (4-isopropyl-3-methyl-sulphonylbenzoyl guanidine methanesulphonate) and KB-R9032 (N-(4-isopropyl-2,2-dimethyl-3-oxo-3, 4-dihydro-2H-benzo-[1,4]oxazine-6-carbonyl) guanidine methanesulphonate) were used as pharmacological tools for the analysis. ET-1 at 0.1 nM induced an increase in Ca(2+) transients by 45.6%, while it increased cell shortening by 109.6%. For a given increase in cell shortening, the ET-1-induced increase in Ca(2+) transients was much smaller than that induced by isoprenaline (ISO, 10 nM). Pretreatment with HOE642 and KB-R9032 (1 microM) inhibited the increase in cell shortening induced by 0.1 nM ET-1 by 51 and 65. 4%, respectively, without a significant alteration of ET-1-induced increase in Ca(2+) transients. HOE642 and KB-R9032 did not affect baseline levels of cell shortening and peak Ca(2+) transients, and the effects of ISO (10 nM). These results indicate that activation of Na(+)/H(+) exchange by ET-1 may play an important role in the positive inotropic effect and the ET-1-induced increase in myofilament Ca(2+) sensitivity in rabbit ventricular myocytes.

Animals↗
PubMed2000

Selective expansion of T cells in gingival lesions of patients with chronic inflammatory periodontal disease.

Chronic inflammatory periodontal diseases are characterized by a cellular infiltrate and are similar in many respects to other chronic inflammatory diseases. While periodontopathic bacteria have been recognized as the principal causative agent and the immune response to these bacteria is thought to be responsible for the tissue destruction, the full aetiological spectrum is still incompletely understood. In addition to many cell types such as polymorphonuclear leucocytes and macrophages, T cells have been implicated in pathogenesis and are considered to have regulatory roles in progression of the disease. Based on our recent studies demonstrating biased expression of several Vbeta families in periodontitis tissues, the aim of this study was to characterize further the T cells relevant to the disease process by reverse transcription-polymerase chain reaction-single-strand conformation polymorphism (RT-PCR-SSCP) and subsequent nucleotide sequence analysis of complementarity-determining region 3 (CDR3) of the TCR beta-chain. In spite of the likely involvement of numerous bacteria, the present study has clearly shown the oligoclonality of infiltrating T cells in periodontitis lesions in contrast to low clonality of peripheral blood T cells as evidenced by the appearance of distinct bands in gingival tissue samples and smear pattern of peripheral blood on SSCP gels. These were confirmed by the DNA sequencing of the CDR3 of Vbeta16 of selected samples. The analysis of deduced amino acid sequences demonstrated amino acid motifs in the CDR3 region of the periodontitis lesion-derived sequences from each patient. The results indicate that gingival tissue-infiltrating T cells recognizing a limited number of antigens or epitopes are involved in the disease process.

Adult↗
PubMed2000

A clinical diagnosis of diurnal (non-sleep) bruxism in denture wearers.

The purpose of this study was to establish a clinical method for diagnosing diurnal bruxism in denture wearers by recording masseter and anterior temporal electromyograph (EMG) activity. Seven suspected bruxists and five normal patients who wore complete dentures and/or distal extension base removable partial dentures were selected for participation. EMG activity in both the masseter and the anterior temporal muscles was recorded bilaterally during silent reading (10 min), maximal voluntary clenching (MVC), tapping in centric occlusion, lateral movements, chewing and swallowing. No significant differences of EMG activity were found between the groups during tapping, lateral movement, chewing and swallowing (P> 0.05). However, during 10 min of silent reading, a significant difference was found between the groups when comparing masseter muscle activity (P < 0.05). A threshold of 10% of MVC of at least 3-s duration was used to define an individual bruxism event. When the muscle activity recorded during silent reading was further analysed using these criteria, the control group displayed no bruxing activity while the suspected bruxist group displayed a mean frequency of six bruxism events (range 2-10). It was concluded that: (a) masseter muscle activity recorded during 10 min of silent reading showed significant difference between the groups; (b) the criteria selected in this study for the detection of sleep bruxism can also be used to assess diurnal bruxism; and (c) it is possible to diagnose diurnal bruxism in denture wearers by measuring the masseter EMG activity during 10 min of silent reading.

Aged↗
PubMed2000

Differential alteration of cardiotonic effects of EMD 57033 and beta-adrenoceptor agonists in volume-overload rabbit ventricular myocytes.

BACKGROUND: We investigated the effects of EMD 57033, a prototype Ca2+ sensitizer, and beta-adrenoceptor agonists in ventricular myocytes isolated from the volume-overload (V-O) heart failure model of the rabbit. METHODS AND RESULTS: V-O cardiac hypertrophy was induced in rabbits by the formation of an arterio-venous shunt between the carotid artery and jugular vein 12 to 15 weeks after the operation. Ventricular myocytes were enzymically isolated from normal and V-O rabbit hearts. The myocyte was loaded with a fluorescence Ca2+ dye, indo-1, and Ca2+ transients, and cell lengths were measured simultaneously. V-O myocytes were significantly larger than control myocytes. Duration of Ca2+ transients and cell shortening was significantly longer in the V-O myocytes than in control myocytes. Effects of cardiotonic interventions, including EMD 57033, isoproterenol, and dobutamine, on Ca2+ transients and cell shortening in V-O myocytes were compared with those in control rabbit myocytes. Isoproterenol and dobutamine increased the systolic cell shortening and peak Ca2+ transients and abbreviated the duration of cell shortening and Ca2+ transients. These responses were markedly attenuated in V-O myocytes. By contrast, the response of cell shortening to EMD 57033 was unaltered, and the Ca2+ sensitizing effect of EMD 57033 was rather enhanced in V-O myocytes. CONCLUSION: Our results indicate that the effectiveness of Ca2+ sensitizers is maintained in the V-O rabbit hypertrophy and heart failure model in contrast to the blunted response to beta-adrenoceptor agonists, which provides an insight on therapeutic strategy with Ca2+ sensitizers for the treatment of contractile dysfunction in congestive heart failure.

Adrenergic beta-Agonists↗
PubMed2000

Mutations in the hepatocyte nuclear factor-4alpha gene in Japanese with non-insulin-dependent diabetes: a nucleotide substitution in the polypyrimidine tract of intron 1b.

Mutations of the hepatocyte nuclear factor 4 alpha (HNF-4alpha) gene have been demonstrated in maturity-onset diabetes of the young (MODY) 1 families. To investigate the possibility that the HNF-4alpha gene contributes to the onset of non-insulin-dependent diabetes mellitus (NIDDM) in Japanese patients, we screened all exons and flanking introns of this gene for mutations in 100 patients with NIDDM diagnosed after 25 years of age. We identified two missense mutations: M49V in exon 1c and T1301 in exon 4; and two nucleotide substitutions in introns: cytosine to thymidine at -5 nt in intron 1b and adenine to thymidine at -21 nt in intron 5. We screened an additional 220 diabetic subjects for the polymorphism in intron 1b. The c/t substitution in intron 1b was associated with NIDDM. This substitution in the polypyrimidine tract, an important cis-acting element directing intron removal, is likely to influence pre-mRNA splicing of this gene. T1301 in exon 4 was observed in only two diabetic subjects. This mutation could influence the conformation of this peptide, resulting in changes in ligand binding domain function. M49V in exon 1c was found in both diabetic and non-diabetic subjects; isoforms HNF-4alpha 4, 5, and 6 with this mutation may impair glucose metabolism in tissue. In contrast to the primary cause of nonsense and missense mutations of the HNF-4alpha gene in MODY1, the nucleotide substitution in intron 1b may partially contribute to development of NIDDM in combination with other genetic and environmental factors.

Aged↗
PubMed2000

Compilation and characterization of histidine-containing phosphotransmitters implicated in His-to-Asp phosphorelay in plants: AHP signal transducers of Arabidopsis thaliana.

Histidine (His)-to-Aspartate (Asp) phosphorelay signal transduction systems are generally made up of a "sensor histidine (His)-kinase", a "response regulator", and a "histidine-containing phosphotransmitter (HPt)". In the higher plant, Arabidopsis thaliana, results from recent intensive studies suggested that the His-to-Asp phosphorelay mechanism is at least partly responsible for propagation of environmental stimuli, such as phytohormones (e.g. ethylene and cytokinin). Here we compiled the members of the HPt family of phosphotransmitters in Arabidopsis thaliana (AHP-series, Arabidopsis HPt phosphotransmitters), based on both database and experimental analyses, in order to provide a comprehensive basis at the molecular level for understanding the function of the AHP phosphotransmitters that are implicated in the His-to-Asp phosphorelay of higher plants.

Amino Acid Sequence↗
PubMed2000

Influence on myoelectric discharges of anteroposterior displacement of the mandibular position near the tapping point.

The purpose of this study was to examine the influence that the anteroposterior mandibular displacement near the tapping point exerts on the myoelectric activity of masseter and temporal muscles at a specific occluding force and to clarify the possibility of judging the mandibular position by measuring the amount of myoelectric discharge. Eight dentulous subjects were selected for the study. Surface electrodes were placed over the anterior, middle and posterior regions of the masseter muscle and over the anterior, middle and posterior bundles of the temporal muscle. Independently of the measurement region, the changes in the masseter and temporal muscle myoelectric activity which accompanied the anteroposterior mandibular displacement, were low. Moreover, when the mandible was displaced anteroposteriorly, the total amount of the myoelectrical discharge from all the recorded places, as well as the amounts of myoelectrical discharge over the middle part of the masseter muscle and the anterior bundle of the temporal muscle reached their lowest values in those mandibular positions which included the tapping point in less than half of the subjects. Therefore, this study indicates that the possibility of judging anteroposterior mandibular displacement by masseter and temporal muscle electromyography is quite low.

Adult↗
PubMed2000

Polyethylene glycol-modified concanavalin A as an effective agent to stimulate anti-tumor cytotoxicity.

The jack bean lectin, concanavalin A (Con A), was modified with 2,4-bis[O-methoxypoly(ethylene glycol)]-6-chloro-s-triazine, activated PEG2, to form PEG-Con A. The immunoreactivity of PEG-Con A towards anti-Con A antibodies was reduced by increasing the degree of modification of amino groups in the Con A molecule. PEG-Con A had a complete reduction of the immunogenicity in mice and prolonged the clearance-time in blood. Although the mitogenic activity of Con A towards murine spleen cells was reduced by the conjugation with activated PEG2, the administration of PEG-Con A to mice enhanced the anti-tumor cytotoxicity of peripheral lymphocytes against melanoma B16 cells.

Animals↗
PubMed2000

[Genome analysis of Helicobacter pylori by pulsed-field gel electrophoresis].

The molecular epidemiology of total 121 isolates of Helicobacter pylori was analyzed by pulsed-field gel electrophoresis method with restriction enzyme Spe I. Seventy-seven isolates were separated from the clinical samples, 36 isolates from pyloric antrum and the body of stomach of 18 patients and 8 isolates from pyloric antrum of 4 patients that include one colony before and after sterilizing treatment to each patient. Seventy-five in 77 isolates showed different genomic types respectively, and the other 2 isolates had the same genomic type and were suspected to be caused by intersective infection of medical workers or the instruments that used in examination because they were from patients who were examined by gastric microscope in same time and same laboratory. In isolates from 4 patients who were treated by sterilizing method, 2 patients showed same genomic types with that observed before the treatment, and one patient showed an incomplete treatment because the genomic type of its colony was is similar, and another patient could be infected again because its isolates showed different genomic type. In 18 patients whose isolates were separated from pyloric antrum and body of the stomach respectively to each person, isolates of 3 patients showed different genomic types in the two different part of stomach indicating that they had two and more clones of H. pylori.

Cloning, Molecular↗
PubMed2000

Conformation and stability of thiol-modified bovine beta-lactoglobulin.

Bovine beta-lactoglobulin A assumes a dimeric native conformation at neutral pH, while the conformation at pH 2 is monomeric but still native. Beta-lactoglobulin A has a free thiol at Cys121, which is buried between the beta-barrel and the C-terminal major alpha-helix. This thiol group was specifically reacted with 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) in the presence of 1.0 M Gdn-HCI at pH 7.5, producing a modified beta-lactoglobulin (TNB-bIg) containing a mixed disulfide bond with 5-thio-2-nitrobenzoic acid (TNB). The conformation and stability of TNB-bIg were studied by circular dichroism (CD), tryptophan fluorescence, analytical ultracentrifugation, and one-dimensional 1H-NMR. The CD spectra of TNB-bIg indicated disordering of the native secondary structure at pH 7.5, whereas a slight increase in the alpha-helical content was observed at pH 2.0. The tryptophan fluorescence of TNB-bIg was significantly quenched compared with that of the intact protein, probably by the energy transfer to TNB. Sedimentation equilibrium analysis indicated that, at neutral pH, TNB-bIg is monomeric while the intact protein is dimeric. In contrast, at pH 2.0, both the intact beta-lactoglobulin and TNB-bIg were monomeric. The unfolding transition of TNB-bIg induced by Gdn-HCl was cooperative in both pH regions, although the degree of cooperativity was less than that of the intact protein. The 1H-NMR spectrum for TNB-bIg at pH 3.0 was native-like, whereas the spectrum at pH 7.5 was similar to that of the unfolded proteins. These results suggest that modification of the buried thiol group destabilizes the rigid hydrophobic core and the dimer interface, producing a monomeric state that is native-like at pH 2.0 but is molten globule-like at pH 7.5. Upon reducing the mixed disulfide of TNB-bIg with dithiothreitol, the intact beta-lactoglobulin was regenerated. TNB-bIg will become a useful model to analyze the conformation and stability of the intermediate of protein folding.

Animals↗
PubMed2000

[Fetal exposure to endocrine disruptors].

Endocrine disruptors act to alter blood hormone levels or the subsequent action of hormones. Disturbances of hormonal regulation during fetal or postnatal development in human may induce adverse effects, but these adverse effects of endocrine disruptors on humans are subtle. We investigated fetal exposure to endocrine disruptors in Japan by analyzing umbilical cords or cord sera. Many endocrine disruptors including dioxins, polychlorinated biphenyls, organochlorine pesticides, bisphenol A, nonylphenol and phytoestrogen were detected in umbilical cords and cord sera. Here we summarize the present status of fetal exposure to endocrine disruptors in Japan and other countries.

Child Development↗
PubMed1999

Preparation of nanoparticles consisted of poly(L-lactide)-poly(ethylene glycol)-poly(L-lactide) and their evaluation in vitro.

This study describes the preparation and the evaluation of biodegradable poly(L-lactide)-poly(ethylene glycol)-poly(L-lactide) copolymer (PLA-PEG-PLA) nanoparticles containing progesterone as a model drug. PLA and PLA-PEG-PLA copolymers, whose PEG content ranged from 5.2 to 25.8% (w/w), were polymerized in our laboratory. PEG with weight-average molecular weight (Mw) 6600 or 20 000 was introduced as a hydrophilic segment into a hydrophobic PLA homopolymer. A solvent evaporation method was used to prepare the nanoparticles. The drug trapping efficiencies were around 70% and the weight-averaged mean diameters of the nanoparticles were less than 335 nm. The amount of drug released increased as the PEG content and Mw of PLA-PEG-PLA copolymers increased and the total Mw of copolymers of nanoparticles decreased. The initial burst of drug release was reduced by removing the low Mw fraction from the polymer. During the release test, both the extent to which the copolymers were degraded and the size of the nanoparticles were increased slightly by increasing the content of PEG in the polymers. Drug release from the nanoparticles could potentially be controlled by changing the PEG content, PEG Mw and total Mw of the copolymer. The molecular weight distribution (Mw/Mn, Mn: number-average molecular weight) of copolymers was also an important factor for controlled release.

Biocompatible Materials↗