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Biomedical subjects

S Mizuno

Publications and source records attributed to S Mizuno.

At least 127 records · Page 7Linked to original sources
PubMed1999

Emulsion type new vehicle for soft gelatin capsule available for preclinical and clinical trials: effects of PEG 6000 and PVP K30 on physicochemical stability of new vehicle.

To prevent temperature-dependent gel-sol transformation of an o/w emulsion type new vehicle system for a soft gelatin capsule, which may be available for both preclinical and clinical trials, the basic new vehicle formulation (PEG 400:purified water:medium chain triglyceride:polyoxyethylene (20) cetylether = 77:10:10:3) was modified by partially (1, 2 or 3%) replacing PEG 400 with PEG 6000 or PVP K30. When 2 or 3% of PEG 400 was replaced with PEG 6000, temperature-dependent gel-sol transformation was prevented at temperatures below 40 degrees C, and the vehicle appeared to be stable during 8 weeks of storage at 4 to 40 degrees C; the particle size distribution remained unchanged. When 1% of PEG 400 was replaced with PEG 6000, gel-sol transformation was not prevented, though phase separation was not observed at sol state, and the particle size distribution was shifted to be in a larger particle size range after 2 weeks of storage. When PEG 400 was partially (1, 2 or 3%) replaced with PVP K30, temperature-dependent gel-sol transformation was not prevented and, after 2 weeks of storage at 40 degrees C, the particle size distributions of the vehicles were shifted to be in a larger particle size range and the vehicles were separated into two layers. These results suggested that a small amount of PEG 6000 plays an important role in preventing temperature-dependent gel-sol transformation of our developed vehicle system.

Capsules↗
PubMed1999

Plasma endothelin-1 elevation associated with alcohol-induced variant angina.

Vasospastic angina as a result of alcohol ingestion has been reported, but the mechanism of alcohol-induced coronary artery spasm is presently unknown. This report presents 2 cases of alcohol-induced variant angina (VA) with elevated levels of plasma endothelin-1 after alcohol ingestion. In case 1, the plasma endothelin-1 concentration was 3.15 pg/ml before drinking (normal <2.30 pg/ml) and increased to 4.09 pg/ml when measured 5 h after alcohol ingestion. After 2 months of abstinence, the plasma endothelin-1 concentration was 2.88 pg/ml and 6 months after abstinence, it decreased to 2.03 pg/ml (normal range). In case 2, the plasma endothelin-1 concentration was 2.44 pg/ml before drinking and increased to 4.36 pg/ml when measured 5 h after alcohol ingestion. After 2 months of abstinence, the plasma endothelin-1 concentration was 3.04 pg/ml and 6 months after abstinence, it decreased to 2.09 pg/ml (normal range). These 2 cases suggest that a relationship may exist between alcohol-induced VA and elevation in the plasma endothelin-1 concentration after alcohol ingestion.

Aged↗
PubMed1999

Two isoforms of a human actin-related protein show nuclear localization and mutually selective expression between brain and other tissues.

Actin-related proteins (Arps), which are divergent, but apparently homologues to actin, are categorized into 10 classes. While Arps belonging to classes 1-3 were found to be localized in the cytoplasm across eukaryotic phyla, other classes of Arps were found mostly in invertebrates and suggested to contribute to structural modulation of chromatin. Here we report the identification and the characterization of two human isoforms of an Arp not belonging to classes 1-3, which we designated hArpN alpha and hArpN beta. Both proteins were expressed in HeLa cells and they were found localized within the nucleus. Most interestingly, in different human tissues, hArpN alpha and beta were found to be expressed mutually exclusively, and the expression of hArpN alpha was absolutely restricted to the brain. These findings suggest that, in vertebrates, members of distantly related Arps might have tissue-specific functions in the nucleus, possibly through structural modulation of chromatin.

Actins↗
PubMed1999

Medium perfusion enhances osteogenesis by murine osteosarcoma cells in three-dimensional collagen sponges.

In this study, we examined in vitro histogenesis by murine K8 osteosarcoma cells maintained in three-dimensional (3D) collagen sponges. We tested the hypothesis that perfusion of medium enhances cell viability and their biosynthetic activity as assessed by expression of the osteoblastic phenotype and mineral deposition. At intervals, samples were harvested and analyzed histologically, biochemically, and by Northern hybridization for type I collagen, osteopontin (OPN), osteocalcin (OC), and core binding factor alpha 1 (Cbfa1). Histologic evaluation showed greater viability, more alkaline phosphatase (ALP)-positive cells, and more mineralized tissue in the perfused sponges after 21 days. Immunohistological assessment of proliferating cell nuclear antigen revealed 5-fold more proliferating cells in the perfused sponges compared with the controls (p = 0.0201). There was 3-fold more ALP activity in the perfused sponges than the controls at 6 days and 14 days (p = 0.0053). The perfused sponges contained twice the DNA and eight times more calcium than the nonperfused controls after 21 days (p < 0.0001 for both). Northern hybridization analysis revealed more mRNA for collagen type I (2-fold) and 50% more for OC at 14 days and 21 days, whereas OPN and Cbfa1 mRNA expression remained unaffected by the medium perfusion. These results show that medium perfusion had beneficial effects on the proliferation and biosynthetic activity of this osteosarcoma cell line. This system mimics the 3D geometry of bone tissue and has the potential for revealing mechanisms of regulation of osteogenesis.

Alkaline Phosphatase↗
PubMed1999

Possible protective effect of milk, meat and fish for cerebrovascular disease mortality in Japan.

Cerebrovascular disease was a leading cause of death from 1955 to 1980 in Japan. The mortality rate from this disease has decreased sharply in recent decades. This downward trend seems to correspond to the dietary habits of Japanese. Data from a large prospective cohort study were analyzed to examine the association between dietary habits and cerebrovascular disease mortality in Japan. The subjects for this analysis were 223,170 men and women aged 40 to 69 at baseline in December 1965. There were 6,168 deaths in men and 4,862 deaths in women due to cerebrovascular disease (ICD7: 330-334) during the follow-up period from January 1966 to December 1981. Rate ratio (RR) and 95% confidence interval (95% CI) adjusted for sex, attained age, follow-up period, prefecture, cigarette smoking, alcohol drinking and occupation was used for comparison. In this study, the risk of mortality from cerebrovascular disease was inversely associated with dairy milk, meat and fish consumption. Therefore the joint effect of dairy milk, meat and fish (DMF) as animal fat and protein was of interest. In the binary analysis, DMF (D, M, F) means the combination of dairy milk (1-3 times/week or more), meat (1-3 times/week or more) and fish (4 times/week or more). Thus DMF (d, m, f) was the reference group having dairy milk (less than 1 time/week), meat (less than 1 time/week) and fish (less than 4 times/week). For the disease, the RR of DMF (D, M, F) was 0.68 with 95% CI of 0.63 to 0.74, relative to the reference group. Furthermore the joint effect of DMF was more strongly associated with cerebral haemorrhage (ICD7: 331, DMF (D, M, F); RR: 0.63, 95% CI: 0.55-0.70) than with cerebral embolism and thrombosis (ICD7: 332, DMF (D, M, F); RR: 0.79, 95% CI: 0.70-0.89). These findings suggest that the increasing intake of animal fat and/or protein may have played a key role in reducing cerebrovascular disease in Japan.

Adult↗
PubMed1999

Psychosocial development and moral development: an exploratory comparison of adolescents in Japan and America.

Building on previous cross-cultural research, this exploratory study examined the comparative psychosocial and sociomoral development of 46 adolescents--22 Japanese in Japan, 10 Japanese in the United States, and 14 Euro-Americans in the United States. Euro-American participants obtained more positive scores than Japanese in the United States and Japanese in Japan on six psychosocial stages and the total psychosocial score as measured by the Measures of Psychosocial Development. Except in the Contract/Truth domain, all groups scored at a comparable level in sociomoral development as measured by the Sociomoral Reflection Measure-Short Form. Results are discussed in terms of cultural differences affecting adolescent development with implications for research and professional practice.

Adolescent↗
PubMed1999

Stresgenin B, an inhibitor of heat-induced heat shock protein gene expression, produced by Streptomyces sp. AS-9.

Stresgenin B was isolated as an inhibitor of heat-induced heat shock protein (HSP) gene expression from a culture broth of Streptomyces sp. AS-9 by silica gel chromatography and HPLC. The molecular formula of the novel compound was determined as C11H13NO5 by high resolution FAB-MS analysis, and the structure was determined by UV, 1H NMR, 13C NMR, HMQC, HMBC, and NOESY spectra. Stresgenin B inhibited heat-induced luciferase reporter-gene expression directed by the human hsp70B promoter in Chinese hamster ovary (CHO) cells at concentrations lower than the concentrations for inhibition of dexamethasone-induced luciferase reporter-gene expression directed by the mouse mammary tumor virus (MMTV)-LTR promoter. The inhibition of heat-induced reporter gene expression was evident even when cells were exposed to stresgenin B only during heat stress treatment. Moreover, the compound inhibited heat-induced syntheses of hsp72/73, hsp90, and hsp110 and thereby suppressed the induction of thermotolerance. Stresgenin B showed moderate cytotoxic activities against several neoplastic cell lines and also showed antibacterial activities against Micrococcus luteus, Bacillus subtilis and Staphylococcus aureus strains.

Animals↗
PubMed1999

Role of tumor necrosis factor-alpha in Mycobacterium-induced granuloma formation in tumor necrosis factor-alpha-deficient mice.

To study the role of TNF-alpha in mycobacterial infection, we generated TNF-alpha-knockout (KO) mice, in which the third and fourth exons of the TNF-alpha gene were disrupted. The C57BL/6 KO mice were injected with virulent Mycobacterium tuberculosis strain Kurono or avirulent bacillus Calmette-Guérin (BCG) Pasteur (10(6) colony-forming units), through the tail veins. The major organs were removed at weekly intervals, and morphologic observation, assays of IL-1, IL-12, IFN-gamma, and inducible nitric oxide synthase mRNA expression, and colony counts in the lungs and spleen were performed. Peritoneal macrophages from BCG- and H37Rv strain-treated mice produced significant levels of nitric oxide after stimulation in vitro. Formation of abscesses was seen only in the Kurono-treated groups, and these abscesses contained large numbers of mycobacteria. The administration of recombinant TNF-alpha significantly ameliorated the mycobacterial lesions. IFN-gamma mRNA was expressed significantly in virulent H37Rv-treated groups with time, and the number of mycobacterial colonies per unit weight increased remarkably with time. Nitric oxide production was not observed in H37Rv-treated groups but was seen in BCG-treated groups. We concluded that TNF-alpha played an important role in protective immunity against virulent mycobacteria. Because avirulent mycobacteria did not induce granulomas in TNF-alpha-KO mice, TNF-alpha played an indirect role in granuloma formation.

Animals↗
PubMed1999

Nocturnal eating/drinking syndrome and neuroleptic-induced restless legs syndrome.

Nocturnal eating/drinking syndrome secondary to neuroleptic-induced restless legs syndrome (RLS) occurred under treatment with low-dose haloperidol in a 51-year-old female schizophrenic patient. Polysomnographic investigation showed a low level of sleep efficacy, periodic leg movements, and a strict relationship between nocturnal eating episodes and non-rapid eye movement sleep. Her nocturnal eating and RLS were completely inhibited by clonazepam treatment. To our knowledge, this is the first published case of nocturnal eating/drinking syndrome secondary to neuroleptic-induced RLS.

Antipsychotic Agents↗
PubMed1999

[Recent progress in akathisia].

Neuroleptic-induced akathisia should be definitely diagnosed as acute, tardive, withdrawal, and chronic. The diagnostic assessment must be identified from the subjective report and objective features. Various assessments of measuring akathisia can be clinically used by instrumental methods and rating scales. The pharmacological basis of neuroleptic-induced akathisia is the inhibition of the dopamine receptors in the brain. The pathogenesis of neuroleptic-induced akathisia may involve GABAergic hypoactivity, noradrenergic hyperactivity, and serotonergic dysfunction in CNS. Iron deficiency and hyperglycemia may be risk factors of neuroleptic induced akathisia in relation to the dopamine function in the brain. Neurological disorders may be associated with the development of a syndrome resembling drug-induced akathisia. The lesion of the thalamic nuclei would originally produce the syndrome. The difference between acute and tardive akathisia on the strategy of the drug treatment should be sufficiently comprehended. In particular, the long-term use of anticholinergic drugs and benzodiazepines should not be prevailed.

Akathisia, Drug-Induced↗
PubMed1999

Comparison of 1-week and 2-week triple therapy with omeprazole, amoxicillin, and clarithromycin in peptic ulcer patients with Helicobacter pylori infection: results of a randomized controlled trial.

This study was a comparison of 1-week and 2-week triple therapies with omeprazole, amoxicillin, and clarithromycin (OAC) in patients with peptic ulcer disease and Helicobacter pylori infection. A total of 147 peptic ulcer patients with H. pylori infection assessed by histology and culture were randomly treated with omeprazole 20mg bid + amoxicillin 1000mg bid + clarithromycin 400mg bid for either 1 week (OAC1w) or 2 weeks (OAC2w). Both groups then received omeprazole 20mg daily for 2 weeks followed by ranitidine 300mg daily for 4 weeks. Eradication of H. pylori was assessed by histology, culture, and the 13C-urea breath test (13C-UBT) at least 6 weeks after cessation of antimicrobial therapy. Intention-to-treat eradication rates were 78.2% (95%CI 69%-87%) with OAC1w and 88.4% (95%CI 81%-96%) with OAC2w. Per-protocol eradication rates were 86.0% (95%CI 78%-94%) with OAC1w, 97.0% (95%CI 93%-100%) with OAC2w. There was no significant difference in the eradication rates between OAC1w and OAC2w. Side effects were mild and self-limiting in both groups. In conclusion, both 1- and 2-week triple therapy with OAC are well tolerated and provide good eradication rates in peptic ulcer patients in Japan. The eradication rate of the 2-week regimen was higher than that of the 1-week regimen, but the difference was not statistically significant. Further studies including long-term economic considerations are required to determine the optimal duration of treatment.

Adolescent↗
PubMed1998

Intracoronary aspiration thrombectomy for acute myocardial infarction.

To investigate the pathogenesis of acute myocardial infarction (AMI) and values of intracoronary aspiration thrombectomy (ICAT), we applied ICAT to reperfusion therapy using generally available intracoronary catheters to aspirate intracoronary occlusive tissues. We assigned ICAT or primary percutaneous transluminal coronary angioplasty (PTCA) to patients with evolving AMI (Thrombolysis In Myocardial Infarction (TIMI) trial grade 0), and investigated primary histopathologic, clinical, and angiographic outcomes in 43 patients treated with ICAT alone or followed by PTCA, and compared the outcomes with those in 48 patients treated with primary PTCA. No major complications (procedural death, emergent bypass graft surgery) occurred. Reconalization (TIMI grade 3 and 2) was achieved in 25 patients (58%) with ICAT alone and in 39 patients (91%) with ICAT alone or followed by PTCA. Aspirated thrombi were defined as recent thrombi in 21 cases (49%), atheroma in 6 (14%), no thrombi in 13 (30%), and organized thrombi in 1 case. In cases of recent thrombi, ICAT alone provided recanalization more frequently than in those of atheroma or no thrombi (18 of 21 [86%], 3 of 6 [50%], 4 of 13 [31%], respectively; p < 0.05; recent thrombi vs atheroma or no thrombi). There were no significant differences in primary recanalization rate (ICAT alone or followed by PTCA vs primary PTCA; 91% vs 92%) or incidence of complications between the 2 strategies. These results indicate that although the pathogenesis of AMI is heterogeneous in each individual case, intracoronary thrombus contributes little to the pathogenesis of average AMI, and therefore mechanical approaches may be feasible to maximize reperfusion therapies for AMI.

Angioplasty, Balloon, Coronary↗
PubMed1998

The mouse Lect2 gene: cloning of cDNA and genomic DNA, structural characterization and chromosomal localization.

We previously purified bovine leukocyte cell-derived chemotaxin 2 (LECT2) as a 16 kDa-secreted protein with a neutrophil chemotactic activity. LECT2 protein is thought to be multifunctional, since it was recently found to be identical to chondromodulin-II, a growth stimulator of chondrocyte cells. We report here the cloning and structural analysis of mouse Lect2 cDNAs and genomic DNA, and chromosomal mapping. Two types of mouse Lect2 cDNAs were cloned: one encoded the mouse counterpart of human and bovine LECT2 proteins, and the other encoded a queer type LECT2 protein whose amino-acid sequence in the carboxy terminus was different from that of the normal type LECT2 protein. The mouse Lect2 gene spanned approx. 8 kb and consisted of five exons and four introns. The genomic organization revealed that two type transcripts arose by an alternative splicing event involving exon 4. A primer extension analysis revealed that several transcription initiation sites occurred within 60-210 nucleotides upstream from the translation initiation codon. The mouse Lect2 gene was mapped to a region adjacent to D13Mit13, D13Mit21 and Il-9 on chromosome 13 by interspecific backcross mapping.

Amino Acid Sequence↗
PubMed1998

1a-docosahexaenoyl mitomycin C: a novel inhibitor of protein tyrosine kinase.

A series of derivatives of mitomycin C conjugated with various fatty acids at position 1a was synthesized and the effect of these compounds on protein kinase activities was evaluated. 1a-Docosahexaenoyl mitomycin C (DMMC) selectively inhibited protein tyrosine kinase (PTK) activity in the postnuclear fraction of v-src-transformed NIH 3T3 cells although neither derivatives conjugated with other fatty acids or docosahexaenoic acid or mitomycin C did not. DMMC inhibited the activity of calmodulin-dependent kinase III and protein kinase A very weakly, and only barely affected protein kinase C activity. DMMC also attenuated autophosphorylation of immunoprecipitated p60v-src irreversibly. The addition of thiol compounds to the reaction mixture reversed the inhibition by DMMC, suggesting that some thiol moiety of PTK protein might be involved. DMMC also inhibited kinase activity of p210bcr-abl immunoprecipitated from the lysate of K562 cells. These results indicate that DMMC is a novel inhibitor of PTK.

3T3 Cells↗
PubMed1998

Chicken chromobox proteins: cDNA cloning of CHCB1, -2, -3 and their relation to W-heterochromatin.

Three clones for chicken chromobox proteins were obtained from liver and ovary cDNA libraries. pCHCB1 and pCHCB2 encode polypeptides showing 96 and 95% identity with mouse M31 and M32, respectively, which are homologues of Drosophila heterochromatin protein 1 (HP1), and pCHCB3 encodes a polypeptide whose sequences of chromobox and C-terminal region show high-level similarities with those of mouse M33, Drosophila polycomb (Pc) protein, and Xenopus Pc homologue. When these cDNAs were expressed in female chicken embryonic fibroblasts (CEFs) as GFP-fused or HA-tagged proteins, all three proteins were found to be localized in nuclei. Among them, CHCB1 associates with brightly stained spots with 4', 6-diamidino-2-phenylindole (DAPI), suggesting its accumulation on heterochromatins. One of those spots was identified as W-heterochromatin. When CHCB1 lacking the N-terminal basic/acidic region or a part of the chromobox region was overexpressed in CEFs, W-heterochromatin became partially or extensively decondensed in the majority of nuclei. Overexpression of CHCB3 lacking a part of the chromobox did not cause decondensation of W-heterochromatin. Specific antisera raised against a part of CHCB1 or CHCB2, produced in Escherichia coli, detected protein species having apparent molecular masses of 25 kDa or 22 plus 23 kDa, respectively, in the subnuclear fraction containing the majority of chromatin from female chicken MSB-1 cells.

Amino Acid Sequence↗
PubMed1998

Hepatocyte growth factor prevents renal fibrosis and dysfunction in a mouse model of chronic renal disease.

Chronic renal disease (CRD) is generally thought to be incurable, except through renal transplantation, and the number of patients with CRD is on the increase. Glomerulosclerosis and tubulointerstitial fibrosis represent the morphological equivalent of end-stage CRD. In this study, we demonstrated the preventive effect of hepatocyte growth factor (HGF) on the progression of renal dysfunction and fibrosis, using a spontaneous mouse model for CRD (ICGN strain). The mice progressively developed glomerular sclerotic injury, tubular atrophy, and renal dysfunction until they were 17 wk of age. When recombinant HGF was injected into these mice during a 4-wk-period (from weeks 14-17 after birth), DNA synthesis of tubular epithelial cells was found to be 4.4-fold higher than in mice without HGF injection, thereby suggesting tubular parenchymal expansion promoted by HGF. Notably, HGF suppressed the expression of transforming growth factor-beta and of platelet-derived growth factor as well as myofibroblast formation in the affected kidney. Consequently, the onset of tubulointerstitial fibrosis was almost completely inhibited by HGF, while HGF attenuated the progression of glomerulosclerosis, both leading to preventing manifestation of renal dysfunction. From our results, supplement therapy with HGF may be taken into consideration as a novel option for prevention and treatment of CRD.

Animals↗