Search PubMed⌕ Search

Biomedical subjects

M Mizuno

Publications and source records attributed to M Mizuno.

At least 163 records · Page 9Linked to original sources

Properties and cytotoxicity of water soluble Na2O-CaO-P2O5 glasses.

Various compositions of Na2OCaO-P2O5 glasses are prepared to estimate glass formation, dissolution properties and cytotoxicity. In the wide composition range of 40 mol% of P2O5 or more, clear glass samples were obtained. The estimated glass forming region was consistent with other ternary phosphate glass systems. The glass transition temperatures and crystallization temperatures decreased with increasing P2O5 content and increased with CaO content. Dissolution properties in distilled water and simulated body fluid (SBF) were measured. In distilled water, CaO free glasses showed extremely fast dissolution. The dissolution rate decreased with increasing CaO content and decreasing P2O5 content. This composition effect results from cross-link formation between the non-bridging oxygens of two different chains by Ca2+ ions which improves the phosphate network strength. In SBF, the dissolution rate followed a similar trend, but glass dissolution was suppressed. This suppression occurred due to the existence of soluble species of glass such as Na+, Ca2+ and HPO(2-)4. The cytotoxicity decreased with increasing CaO content and with decreasing PO2.5 content. This was the result of a change in pH and ion concentration in the medium.

Biocompatible Materials↗

Decay-accelerating factor (DAF) in stool specimens as a marker of disease activity in patients with ulcerative colitis (UC).

Colonic epithelial cells of patients with UC express DAF in relation to the severity of mucosal inflammation. The aim of this study was to determine whether this factor in stool could be used as a marker of disease activity in UC patients. Stool DAF was measured by use of an immunoassay in 181 stool specimens obtained from 55 patients with UC of various levels of disease activity. Stool DAF concentrations in patients whose UC was active (0.0-785.6 ng/g stool; median 47.1 ng/g; n = 115) were significantly higher than concentrations in patients whose disease was inactive (0.0-48.6 ng/g; median 0.0 ng/g; n = 66) (P < 0.0001). Values in active UC patients also were higher than those in control patients with diarrhoea (0.0-30.0 ng/g; median 0.0 ng/g; n = 26) (P < 0.0001) and in control subjects without apparent colorectal disease (0-20.4 ng/g; median 0.0 ng/g; n = 44) (P < 0.0001). The elevated levels of stool DAF obtained from UC patients in relapse declined markedly in specimens collected after the disease went into remission following medical therapy. Stool DAF levels correlated with the severity of endoscopic and histological findings and the degree of DAF expression on the colonic epithelia. Our results suggest that the measurement of stool DAF is useful as a non-invasive means of monitoring intestinal disease activity in patients with UC.

Adolescent↗

Cytokine-stimulated release of decay-accelerating factor (DAF;CD55) from HT-29 human intestinal epithelial cells.

Expression of DAF (CD55) is enhanced on colonic epithelial cells of patients with ulcerative colitis (UC), and stool DAF concentrations are increased in patients with active disease. Cytokines are known to modulate DAF expression in various human cells, and lesions of UC reveal altered profiles of cytokine production. In this study, we evaluate the effects of various cytokines, IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, and interferon-gamma (IFN-gamma), on the synthesis and kinetics of DAF protein in HT-29 human intestinal epithelial cells. Using flow cytometry and an ELISA, we found that HT-29 cells constitutively express DAF on the cell surface and spontaneously release DAF into the culture supernatant under standard culture conditions. When the culture supernatant was centrifuged at 100000g, nearly a half of DAF was precipitated, indicating that one half of the released DAF was present as a membrane-bound form and the other half as a soluble form. Analysis of the culture supernatant of biotin surface-labelled HT-29 cells suggested that the soluble form DAF was derived by secretion from within the cell or by cleavage from the cell surface. Among the cytokines, IL-4 markedly, and IL-1beta moderately, enhanced the expression and the release of DAF. Actinomycin D, cycloheximide, and brefeldin A inhibited the increase in DAF release induced by IL-4 and IL-1beta stimulation. These results suggest that DAF is released from intestinal epithelial cells in response to cytokine stimulation and that IL-4 and IL-1beta are possible cytokines involved in DAF release into the colonic lumen of patients with UC.

Anti-Bacterial Agents↗

Ascorbate peroxidase and catalase cooperate for protection against hydrogen peroxide generated in potato tubers during low-temperature storage.

We investigated the behavior of the antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), and ascorbate peroxidase (APx), in potato tubers during storage at low temperature. SOD activity increased temporarily within 3 weeks and was higher at 1 degree C than at 20 degrees C. APx activity also increased more at low (1 degree C) than at higher temperatures (5 and 20 degrees C). The contents of ascorbic acid (AsA), which is the substrate of APx, decreased immediately within 3 weeks and then gradually decreased until 15 weeks. The activity of CAT, the other enzyme which can scavenge hydrogen peroxide, decreased once in the first six weeks and thereafter increased to 15 weeks. Thus, the enhancement of the active oxygen-scavenging system that was induced by low temperature in potato tubers could result not only in a decrease of AsA but also in combined increases in APx and CAT activity whose manners were different.

Ascorbate Peroxidases↗

Glycogen depletion and lactate accumulation in human intercostal muscles after administration of succinylcholine.

I.m. glycogen content, lactate concentration and staining intensity for glycogen in slow- (ST) and fast-twitch (FTa and FTb) fibres were determined in the external and internal intercostal muscles after thoracotomy. Thirteen patients received a precurarizing dose of a non-depolarizing neuromuscular blocking agent followed by the depolarizing agent, succinylcholine, to facilitate intubation of the trachea (succinylcholine group). Nine patients received pancuronium or gallamine (control group). There were no significant differences in ventilatory functional capacity between the two groups. In the external intercostal muscles, lower i.m. glycogen content was observed in the succinylcholine compared with the control group (P < 0.05). I.m. glycogen was depleted from the FT fibres and in particular from FTb fibres, while little depletion was noted in ST fibres. In both the external and internal intercostal muscles, a higher lactate concentration was observed in the succinylcholine than in the control group (P < 0.05). The results indicate that the use of succinylcholine for tracheal intubation stimulated breakdown of i.m. glycogen, particularly in fast-twitch muscle fibres, and caused accumulation of lactate in intercostal muscles.

Adult↗

Adeno-associated virus vector containing the herpes simplex virus thymidine kinase gene causes complete regression of intracerebrally implanted human gliomas in mice, in conjunction with ganciclovir administration.

Adeno-associated virus (AAV) has attracted considerable interest as a potential vector for gene therapy because of its wide host range, high transduction efficiency, and lack of cytopathogenicity. In this experiment, we evaluated the efficacy of AAV vector containing the herpes simplex virus thymidine kinase (HSV-tk) gene on human gliomas transplanted into the brain of nude mice. Complete regression of the tumors was observed after multiple AAV-tk injections followed by intraperitoneal ganciclovir (GCV) administration, and the survival of mice treated with AAV-tk vector and GCV administration was markedly prolonged. These results suggest that AAV-tk vectors may be useful for gene therapy against malignant gliomas in humans.

Animals↗

Improvement of transduction efficiency of recombinant adeno-associated virus vector by entrapment in multilamellar liposomes.

Recombinant adeno-associated virus (AAV) has attracted considerable interest as a potential vector for human gene therapy, but its transduction efficiency is quite low. The present study demonstrated AAV vector-associated liposomes to be more effective for in vitro gene transfer to human glioma cells than are liposomes containing plasmid DNA. Using vector-associated liposomes increased the transduction efficiency more than 10-fold compared to liposomes containing plasmid DNA and more than 6-fold compared to AAV alone. From these results, AAV vector-associated liposomes appear to be a good candidate for in vivo gene delivery to human gliomas.

DNA, Viral↗

Genetic and serological evidence for multiple instances of unrecognized transmission of hepatitis C virus in hemodialysis units.

We investigated the unrecognized patient-to-patient transmission of hepatitis C virus (HCV) in hemodialysis units by performing phylogenetic and serological analyses of hypervariable region 1 (HVR1) of HCV. Of the 62 patients in one center, 11 were positive for HCV RNA. A total of 24 HVR1 sequences, including the minor population of sequences of HCV isolates, from each patient were closely related and classified into five clusters by phylogenetic analysis. Of the 11 patients, 5 were infected with multiple clusters of HCV. Two patients were infected with HCV during an 18-month interval between examinations, and these HVR1 sequences fell into one of the five clusters. In another hemodialysis center, 5 of the 20 patients were HCV RNA positive, and two HVR1 sequences were found to be closely related and phylogenetically derived from the same cluster. The antibody responses of these patients to the HVR1 peptides representative of the genetic clusters revealed exactly the same clustering as that shown by phylogenetic analysis. These findings suggest that phylogenetic and serological analyses of HVR1 sensitively detect unrecognized and multiple transmission of HCV occurring within the same room in hemodialysis centers. Fingerprinting analyses using hypervariable regions of infectious agents are useful in identifying the precise route of transmission of infection.

Amino Acid Sequence↗

'Alice in Wonderland' syndrome as a precursor of depressive disorder.

A 54-year-old Japanese businessman who was found to exhibit the 'Alice in Wonderland' syndrome and went on to develop a depressive disorder is described. Lengthening and shortening of time experience continued intermittently for about 3 months, and metamorphopsia, distortion of body image, and the quick-motion phenomenon (alteration in time sense) persisted for almost 2 days without interruption. There were no abnormal physical findings. The authors review studies on 'Alice in Wonderland' syndrome and suggest that depressive illness may be a causal factor.

Body Image↗

Polysaccharides from Agaricus blazei stimulate lymphocyte T-cell subsets in mice.

Subset analysis of splenic lymphocytes using flow cytometry showed that the percentages of Thy1.2-(pan T-cells), L3T4-(CD4, helper T-cells), and Lyt2-(CD8, cytotoxic T-cells) positive cell populations were significantly increased in mice orally administered a hot water-soluble fraction from Agaricus blazei as compared with mice treated only with saline. 13C-NMR data indicates that the main component in the active polysaccharide is the complex of alpha-1,6- and alpha-1,4-glucan, which had already been shown to have anti-tumor activity against Sarcoma 180. It seems that the polysaccharide from Agaricus blazei may be an effective prophylactic, protecting humans against cancer by stimulating lymphocytes such as cytotoxic T-cells.

Adjuvants, Immunologic↗

Surgical indications for neonatal ovarian cysts.

Ante- or neonatal ovarian cysts can be often diagnosed by routine ultrasonography. Small simple ovarian cysts, which can be followed with serial ultrasonography, usually resolve spontaneously. Large simple cysts and complicated cysts should undergo surgical treatment to reduce the potential for serious complications. Seventeen ovarian cysts were experienced between 1983 and 1997. Sixteen cases underwent surgical treatment at less than 1 month of age according to our protocols. In this report, we reviewed these cases for clinical presentation, ultrasound data, management, intraoperative findings, complications, and outcome. At operation, nine of them showed torsion, and seven of them showed necrotic changes. Only five of them was considered to fall into torsion by preoperative ultrasonography. In five cases whose blood flow could not improve after reduction of torsion, salpingo-oophorectomy was performed. We consider that small simple ovarian cysts under 4 cm in diameter can be observed carefully with serial ultrasonography. But, not only complicated ovarian cysts and simple cysts over 5 cm in diameter, but smaller cysts showing no decrease in size should be considered for surgical indication to rescue the ovarian tissue.

Female↗

Growth inhibition of experimental glioma by human interferon-beta superinduced by cationic liposomes entrapping polyinosilic:polycytidilic acid.

Intracellular production of human interferon-beta (HuIFN-beta) was enhanced in three glioma cell lines (U251-MG, U251-SP, and U251-NN) using modified superinduction with cationic liposomes containing polyinosilic:polycytidilic acid (polyI:polyC), initially given with cycloheximide, to decrease the toxicity due to polyI:polyC. Modified superinduction had a significantly (p < 0.02-0.0001) greater inhibitory effect on all three glioma cell lines, and less toxicity than superinduction. A pilot trial in experimental gliomas implanted into nude mice was also performed. Superinduction including intratumoral injection of cationic liposomes containing polyI:polyC resulted in growth inhibition of U251-NN tumors and eradication of U251-SP tumors. Weight gain in mice was not inhibited by modified superinduction. Cationic liposomes decreased drug toxicity, and may help to target tumor cells in the modified superinduction of endogenous HuIFN-beta production.

Animals↗

Gene therapy of central nervous system tumors.

Recently, remarkable advances have been achieved in molecular and genetic researches of different kinds of general diseases, as well as in basic and clinical studies using gene therapy for central nervous system diseases. For brain tumors, clinical trials have been already started in more than 10 clinical protocols and more than 100 patients with malignant brain tumors. Nevertheless, there are still major issues that remain to be resolved for achieving better clinical results, such as delivery system of genetic material, regulatory methods of the intracellular expression of the transgene, antitumor efficacy, and tumor selectivity. In this paper, molecular genetic studies and the current state of gene therapy for neurological diseases, especially brain tumors, are described, and the future direction of this fascinating approach is discussed.

Animals↗

Analyses of neuro-otological complications after radiosurgery for acoustic neurinomas.

PURPOSE: To find out the optimum treatment parameters and the proper indications for treatment of acoustic neurinomas, univariate and multivariate actuarial analyses of neuro-otological complications after stereotactic radiosurgery for acoustic neurinomas were performed. METHODS AND MATERIALS: The subjects were 46 patients with acoustic neurinomas who underwent unilateral radiosurgery between June 1990 and June 1994 and were followed up at the University of Tokyo. Age ranged from 13 to 77 years (median, 54 years). Tumor diameter ranged from 0 to 25 mm (mean, 12 mm) at the cerebellopontine angle and from 2 to 15 mm (mean, 8.3 mm) in the internal auditory meatus. Maximum tumor doses ranged from 20 to 40 Gy (mean, 31.4 Gy), and peripheral doses from 12 to 25 Gy (mean, 16.8 Gy). One to eight isocenters were used (mean, 3.2). Median follow-up was 39 months. Eight events concerning neuro-otological complications were chosen, and the potential risk factors for them were analyzed by the actuarial analyses (univariate and multivariate). The events examined include hearing loss, vestibular function loss, facial palsy, and trigeminal nerve dysfunction. In order to point out potential risk factors for neuro-otological complications, univariate analyses were performed using both the Wilcoxon test and the log rank test, and multivariate analyses were performed with the Cox proportional hazards model. Variables nominated as potential risk factors were 1) demographic variables such as patient age and sex, 2) tumor dimensions, 3) treatment variables such as tumor doses and number of isocenters, and 4) pretreatment hearing levels. A variable with significant p-values (p < 0.05) in two or more of the three actuarial analyses (two univariate and one multivariate) was considered a possible risk factor. RESULTS: The possible variables that increase the risk for each event analyzed were: neurofibromatosis type II (NF2) and the number of isocenters for total hearing loss; experience of prior operation, the tumor diameter in the internal auditory meatus, and NF2 for hearing threshold elevation; peripheral tumor dose for vestibular function loss; patient age or midporus transverse tumor diameter (the two variables were correlated), and the number of isocenters for facial palsy; and the number of isocenters for trigeminal neuropathy. CONCLUSION: NF2 and the tumor diameter were the common risk factors for hearing loss in previous studies and ours. For the 5th/7th nerve dysfunction, the tumor diameter was the common risk factor. The risk of using more isocenters remains controversial. The difference in risk factors for hearing impairment and vestibular function loss suggests different mechanisms for the two. Further studies with larger populations and longer follow-up periods are required in order to draw conclusions on the risk factors in radiosurgery.

Adolescent↗

The complete genome sequence of the gram-positive bacterium Bacillus subtilis.

Bacillus subtilis is the best-characterized member of the Gram-positive bacteria. Its genome of 4,214,810 base pairs comprises 4,100 protein-coding genes. Of these protein-coding genes, 53% are represented once, while a quarter of the genome corresponds to several gene families that have been greatly expanded by gene duplication, the largest family containing 77 putative ATP-binding transport proteins. In addition, a large proportion of the genetic capacity is devoted to the utilization of a variety of carbon sources, including many plant-derived molecules. The identification of five signal peptidase genes, as well as several genes for components of the secretion apparatus, is important given the capacity of Bacillus strains to secrete large amounts of industrially important enzymes. Many of the genes are involved in the synthesis of secondary metabolites, including antibiotics, that are more typically associated with Streptomyces species. The genome contains at least ten prophages or remnants of prophages, indicating that bacteriophage infection has played an important evolutionary role in horizontal gene transfer, in particular in the propagation of bacterial pathogenesis.

Bacillus subtilis↗

Hedgehog and patched gene expression in adult ocular tissues.

We analysed the expression of members of the hh gene family in adult ocular tissues of newt, frog and mouse by RT-PCR method. Shh displayed restricted expression in the neural retina that was conserved in each species analyzed. X-bhh, X-chh and mouse Ihh were detected in the iris and in the retinal pigment epithelium, while mouse Dhh was detected additionally in the neural retina and faintly in the cornea. We also found that two types of ptc genes, potential hh targets and receptors, were expressed in these tissues, suggesting the presence of active hh signalling there.

Amino Acid Sequence↗