Biomedical subjects

S Okada

Publications and source records attributed to S Okada.

At least 469 records · Page 26Linked to original sources

PubMed1997

Zonisamide monotherapy in newly diagnosed infantile spasms.

PURPOSE: We determined the short-term efficacy of zonisamide (ZNS) monotherapy in newly diagnosed patients with infantile spasms (IS). METHODS: Eleven hospitals participated in this open, prospective trial. ZNS 3-10 mg/kg/day was administered as the second-choice drug to 11 newly diagnosed patients with IS (cryptogenic 3, symptomatic 8) who failed to respond to high-dose vitamin B6. RESULTS: Four infants with symptomatic IS had cessation of spasms and disappearance of the hypsarrhythmia. In these responders, the spasms ceased after a few days (1-5 days) of treatment at a dose of ZNS 4-5 mg/kg/day which produced plasma ZNS concentrations ranging from 5.2 to 16.3 microg/ml (mean 9.8 microg/ml). There were two relapses (50%) 4-6 weeks after cessation of seizures, however. Relapse was predicted by effects of ZNS on EEG; the 2 infants in whom an abnormal EEG persisted had relapses, whereas the 2 whose EEG normalized remained seizure-free (follow-up 20 and 26 months). No adverse reactions were noted. CONCLUSIONS: ZNS may be effective in the initial treatment of selected patients with IS.

Adrenocorticotropic Hormone↗

PubMed1997

Effects of MRI abnormalities on WAIS-R performance in solvent abusers.

OBJECTIVE: To clarify how chronic solvent abuse affects cognitive function using magnetic resonance imaging as an index of brain damage. MATERIAL AND METHODS: A total of 25 chronic solvent abusers underwent magnetic resonance imaging with quantitative neurometry and Wechsler Adult Intelligence Scales revised. RESULTS: The abusers with white matter change (n=10) showed significantly (P<0.05) lower performance IQ, especially in Digit Symbol subtest (P<0.01). Also, the severity of pontine atrophy was significantly correlated with PIQ (r=0.60, P<0.01). CONCLUSIONS: These data indicate that solvent abuse causes the decline in the test performance reflecting cognitive and fine motor dysfunction and that white matter changes and pontine atrophy may have some roles in this decline.

Adult↗

PubMed1997

Characterization of a gene cluster for glycogen biosynthesis and a heterotetrameric ADP-glucose pyrophosphorylase from Bacillus stearothermophilus.

A chromosomal region of Bacillus stearothermophilus TRBE14 which contains genes for glycogen synthesis was cloned and sequenced. This region includes five open reading frames (glgBCDAP). It has already been demonstrated that glgB encodes branching enzyme (EC 2.4.1.18 [H. Takata et al., Appl. Environ. Microbiol. 60:3096-3104, 1994]). The putative GlgC (387 amino acids [aa]) and GlgD (343 aa) proteins are homologous to bacterial ADP-glucose pyrophosphorylase (AGP [EC 2.7.7.27]): the sequences share 42 to 70% and 20 to 30% identities with AGP, respectively. Purification of GlgC and GlgD indicated that AGP is an alpha2beta2-type heterotetrameric enzyme consisting of these two proteins. AGP did not seem to be an allosteric enzyme, although the activities of most bacterial AGPs are known to be allosterically controlled. GlgC protein had AGP activity without GlgD protein, but its activity was lower than that of the heterotetrameric enzyme. The GlgA (485 aa) and GlgP (798 aa) proteins were shown to be glycogen synthase (EC 2.4.1.21) and glycogen phosphorylase (EC 2.4.1.1), respectively. We constructed plasmids harboring these five genes (glgBCDAP) and assayed glycogen production by a strain carrying each of the derivative plasmids on which the genes were mutated one by one. Glycogen metabolism in B. stearothermophilus is discussed on the basis of these results.

1,4-alpha-Glucan Branching Enzyme↗

PubMed1997

Quantitative, non-invasive assessment of ventricular septal defect shunt flow by measuring proximal isovelocity surface area on colour Doppler mapping.

OBJECTIVE: To determine whether the proximal isovelocity surface area (PISA) method could be applied to estimate the magnitude of ventricular septal defect (VSD) shunt flow. DESIGN: Prospective analysis of clinical, echocardiographic, and angiographic data. SETTING: University hospital. PATIENTS: 14 children with VSD. METHODS: Colour Doppler images of VSD shunt flow were obtained in parasternal long axis view, four chamber view or both, adjusted to provide the best imaging of flow. The VSD shunt flow rate and shunt volume were calculated as follows: shunt flow rate (SFR) = 2 pi r2 V/BSA in ml/s/m2; shunt volume = SFR x shunt duration time. The shunt volume, shunt fraction, and pulmonary to systemic flow ratio (Qp:Qs) were confirmed by cardiac catheterisation. RESULTS: There was a correlation between shunt variables determined by PISA and those by catheterisation, including shunt volume (r = 0.78, P = 0.001) and shunt fraction (r = 0.74, P = 0.003). Qp:Qs was also significantly correlated with SFR (r = 0.79, P = 0.0007). The SFR was significantly different between the four patients with Qp:Qs < 2.0 (mean (SD) 54 (33) ml/s/m2) and the 10 patients with Qp:Qs > 2.0 (186 (69) ml/s/m2) (P = 0.004). CONCLUSIONS: These data suggest that the PISA method is a reliable non-invasive investigation for the quantitative assessment of VSD shunt flow and provides important information for decisions regarding surgical repair.

Cardiac Catheterization↗

PubMed1997

Transmigration of eosinophils through basement membrane components in vitro: synergistic effects of platelet-activating factor and eosinophil-active cytokines.

Migration of eosinophils through the basement membrane barrier is an important step for their infiltration into tissues. To investigate the mechanism of transmigration, we used a chamber fitted with a Matrigel membrane as a model of the basement membrane. In this model, eosinophils treated with cytokines or chemotactic factors alone did not transmigrate from the upper to the lower chamber. However, platelet-activating factor (PAF) strongly induced transmigration of eosinophils stimulated by interleukin (IL)-5, indicating that both a cytokine and a chemotactic factor are required for eosinophil migration through Matrigel. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-3 also stimulated eosinophil transmigration in the presence of PAF. Of seven eosinophil chemotactic factors tested, leukotriene B4, C5a, RANTES, macrophage inflammatory protein-1alpha, and IL-8 did not induce significant eosinophil transmigration. Only PAF and eotaxin induced transmigration of eosinophils through Matrigel in the presence of IL-5; PAF was more potent than eotaxin at the optimal concentration. In contrast, PAF, eotaxin, and RANTES all potently induced migration of eosinophils through bare membrane in the absence of IL-5. Finally, eosinophil migration through Matrigel was markedly reduced by a combination of anti-CD18 and anti-CD29 monoclonal antibodies, suggesting that it is mediated by beta1- and beta2-integrin adhesion molecules. Our findings demonstrate that eosinophil transmigration through a basement membrane model requires both a specific chemoattractant, such as PAF, and an eosinophil-activating cytokine, such as IL-5. This synergistic effect is likely important in the tissue accumulation of activated eosinophils in allergic and other eosinophil-associated diseases.

Basement Membrane↗

PubMed1997

Migration of eosinophils through basement membrane components in vitro: role of matrix metalloproteinase-9.

In general, inflammatory cells cross basement membranes by producing proteinases. To investigate the role of proteinases in eosinophil basement membrane migration, we studied peripheral blood eosinophils in Matrigel-coated chemotaxis chambers. Electron microscopy showed degradation of the Matrigel layer when eosinophils, added to the upper chamber, transmigrated the membrane in the presence of both platelet-activating factor (PAF) in the lower chamber and interleukin (IL)-5 in both chambers. In the absence of either or both PAF and IL-5, no changes occurred in the Matrigel layer. Matrigel transmigration of eosinophils induced by PAF and IL-5 was inhibited by 1,10-phenanthroline, batimastat, 3,4-dichloroisocoumarin, chymostatin, and a neutralizing antibody for the matrix metalloproteinase (MMP)-9, indicating that serine proteinase(s) and MMP, specifically MMP-9, were involved in the transmigration of eosinophils through Matrigel. In contrast, eosinophil migration through a bare membrane was not affected by batimastat. Using gelatin zymography and immunoblotting, MMP-9 was detected in the migration upper chamber supernatant of the eosinophil transmigration assay and in the conditioned medium of eosinophils. Release of MMP-9 by eosinophils was increased by IL-5, PAF, or both, but the substrate-degrading activity of MMP-9 was increased only in the presence of both IL-5 and PAF, indicating that the releasing and activating mechanisms of MMP-9 are involved in eosinophil basement membrane migration. This study implicates MMP-9 in basement membrane migration of eosinophils and suggests its involvement in inflammatory diseases where tissue eosinophilia plays a role.

Basement Membrane↗

PubMed1997

Insulin stimulates the phosphorylation of the 66- and 52-kilodalton Shc isoforms by distinct pathways.

In contrast to the 52-kDa Shc isoform, insulin stimulation caused a quantitative, time-dependent decrease in the SDS-PAGE mobility of 66-kDa Shc in both Chinese hamster ovary/IR cells and 3T3L1 adipocytes. Alkaline phosphatase treatment and direct phosphoamino acid analysis demonstrated that insulin stimulated an increase in serine phosphorylation of the 66-kDa isoform but not 52-kDa Shc, although the latter displayed a marked increase in tyrosine phosphorylation. To identify the responsible kinase pathway, we compared the effects on 66-kDa Shc serine phosphorylation by insulin, anisomycin, and osmotic shock, agents that specifically activate the ERK, JNK, or both pathways, respectively. Insulin and osmotic shock both stimulated a decrease in 66-kDa Shc mobility, whereas anisomycin had no effect. Furthermore, expression of a dominant-interfering Ras mutant (N17Ras) prevented the insulin-stimulated, but not the osmotic shock-induced serine phosphorylation of 66-kDa Shc. Consistent with a MEK-dependent pathway mediating 66-kDa Shc serine phosphorylation, the specific MEK inhibitor (PD98059) and expression of a dominant-interfering MEK mutant partially inhibited both the insulin and osmotic shock-induced reduction in 66-kDa Shc mobility. In contrast, expression of the MAP kinase phosphatase (MKP-1) completely prevented ERK activation but did not inhibit the serine phosphorylation of 66-kDa Shc. These data demonstrate that insulin stimulates the serine phosphorylation of the 66-kDa Shc isoform through a MEK-dependent mechanism.

3T3 Cells↗

PubMed1997

Band heterotopia or double cortex in a male: bridging structures suggest abnormality of the radial glial guide system.

A moderately retarded Japanese boy, with a normal male karyotype (46,XY), was diagnosed to have a subcortical band heterotopia or double cortex syndrome. The band heterotopia was relatively thick compared with that of other patients reported. On T2-weighted coronal MR sections, there were numerous radial linear structures between the cortex and the band, probably representing the trace of radial fibers. He had no family members with seizures or mental retardation. Over 50 described patients with this malformation have been female except two patients briefly mentioned by several investigators. Band heterotopia or the double cortex syndrome is inherited as a sex-linked dominant condition. Affected mothers may have affected daughters or sons with lissencephaly, suggesting a link between these disorders. This is the first detailed description of a male with band heterotopia.

Cell Movement↗

PubMed1997

Role of Hsp70 subfamily, Ssa, in protein folding in yeast cells, seen in luciferase-transformed ssa mutants.

To investigate the role of constitutive hsp70 in protein folding and to probe the supplementation by other hsps in this folding, yeast cells expressing reduced constitutive hsp70 proteins, ssa1ssa2, were transformed with a plasmid expressing a bacterial luciferase protein. With several independent clone cells of transformants, the levels of luciferase activity and some hsps, such as hsp104, hsp90, hsp70 and hsp26, were examined. The luciferase activity was significantly lower in ssa1ssa2 transformants than in the wild type (wt) cell transformed with the same plasmid. Among several clone cells of ssa1ssa2, the cells with higher luciferase activities exhibited higher amounts of Ssa4 which is known to be expressed instead of lacking Ssa1 and Ssa2. The luciferase activity closely correlated with the amount of Ssa proteins, more than with the amount of other hsps. It is suggested that constitutional Ssa "chaperones" are needed for the folding of proteins and, in cells lacking Ssa1 and Ssa2, the increased Ssa4 is thought to partly compensate for their role in the folding of luciferase in vivo.

HSP70 Heat-Shock Proteins↗

PubMed1997

DNA single-strand breaks in L-132 cells resulting from inhibition of repair polymerization shortly after exposure to dimethylarsinic acid.

DNA single-strand breaks due to the inhibition of repair polymerization in cultured human pulmonary epithelial (L-132) cells after exposure to dimethylarsinic acid (DMAA), a main metabolite of inorganic arsenics in mammals, were examined. The strand breaks were detected by an alkaline elution method with the use of inhibitors of DNA polymerase, aphidicolin (aph) and 2',3'-dideoxythymidine (ddT); the former inhibits DNA polymerases alpha, delta and epsilon, and the latter inhibits DNA polymerase beta. Generally, DNA polymerases delta and epsilon are thought to be associated with necleotide excision (long patch) repair and polymerase beta with base excision (short patch) repair. After exposure of the L-132 cells to 10 mM DMAA, the breaks occurred in a time-dependent manner during incubation for 1-6 h under the inhibition of aph-sensitive polymerases with 50 micrograms/ml aph plus 10 mM hydroxyurea (HU) for the last 1 h of the DMAA exposure. Also, when DNA polymerase beta was inhibited with 10 mM ddT plus 1 microM methotrexate (MTX), the exposure of L-132 cells to 10 mM DMAA for 6 h significantly induced DNA single-strand breaks. An experiment of the co-treatment with both aph and ddT suggested that in the DNA repair process, aph-sensitive polymerases, probably polymerases delta and/or epsilon, and polymerase beta, functioned independently on different lesions induced after exposure to DMAA.

Animals↗

PubMed1997

Cell-nuclear accumulation of 72-kDa stress protein induced by dimethylated arsenics.

The induction and subsequent intracellular distribution of the 72-kDa heat shock (stress) protein (Hsp72) by exposure of cultured human alveolar (L-132) cells to dimethylarsinic acid (DMAA), a main metabolite of inorganic arsenics in mammals, were examined. A significant induction of Hsp72 in the cells was observed by exposure to 10mM DMAA for 6 h. The induction was similar to the case by arsenite for 6 h or by heat treatment at 42 degrees C for 3h. However, the nuclear distribution of Hsp72 differed greatly between DMAA and 42 degrees C treatment or arsenite exposure, i.e., Hsp72 induced by exposure to DMAA accumulated not only in the nucleoli but also in the nucleoplasm, whereas that by 42 degrees C or arsenite exposure did not accumulate in the nucleoplasm. Furthermore, the Hsp72 accumulated in the nucleus by DMAA exposure hardly diffused with the addition of ATP, suggesting that the DMAA-induced Hsp72 strongly binds to some macromolecules in the nucleus. The fact that Hsp72 induced by DMAA exposure accumulated in the nucleus of the cells may reflect a protective response toward the nucleus-specific damaging action of dimethylarsenics.

Adenosine Triphosphate↗

PubMed1997

Sustained release of flufenamic acid from a drug-triacetyl-beta-cyclodextrin complex.

Triacetyl-beta-cyclodextrin (TA-beta-CyD), a hydrophobic cyclodextrin derivative that is insoluble in water, was used to form a complex with flufenamic acid (FA). Complexes of FA with TA-beta-CyD (FA-TA-beta-CyD) at various molar ratios (1:1, 1:2, 1:3) were prepared by a kneading method, using ethanol as a solvent. FA-TA-beta-CyD complex formation was demonstrated by differential scanning calorimetry and powder X-ray diffractometry. The release rate of FA from the FA-TA-beta-CyD complexes was measured in both the Japanese Pharmacopoeia XII 1st fluid pH 1.2 and isotonic phosphate buffer pH 6.8. The release rate of FA from the FA-TA-beta-CyD complexes in the isotonic phosphate buffer pH 6.8 was significantly retarded compared to the release rate of FA from the FA-glucose mixture. After 1 h, 100% of the drug was released from the FA-glucose mixture and 10-25% was released from the complexes. When either the powder of the FA-glucose mixture or the FA-TA-beta-CyD mixture was administered directly into the intraduodenal lumen in rats, the plasma concentration of FA reached a maximum level within 40 min after administration. On the other hand, when the FA-TA-beta-CyD complexes were administered into the intraduodenal lumen, the plasma concentration of FA did not show a sharp peak, but remained at a plateau level (10-18 microg/ml) for 6-8 h. An increased mean residence time of FA following FA-TA-beta-CyD complexes administration was observed; however, the AUC(0-10) for the FA-TA-beta-CyD complexes showed no significant difference from that for the FA-TA-beta-CyD mixture. These results indicate that TA-beta-CyD may serve as a hydrophobic carrier in sustained-release preparations of FA. The drug-TA-beta-CyD complexes may therefore be useful in oral administration to achieve prolonged action and reduced side effects.

Absorption↗

PubMed1997

Application of long-circulating liposomes to cancer photodynamic therapy.

Photodynamic therapy (PDT) as a cancer treatment is notable for its quite low side effects in comparison with those of chemotherapy and radiotherapy. However, the accumulation of porphyrin derivatives used in PDT into tumor tissues is rather low. Since long-circulating liposomes are known to accumulate passively into tumor tissues, we liposomalized a porphyrin derivative, benzoporphyrin derivative monoacid ring A (BPD-MA), and used these liposomes to investigate the usefulness of PDT for tumor-bearing mice. BPD-MA was liposomalized into glucuronate-modified liposomes, which are known to be long-circulating. These liposomes were injected i.v. into Balb/c mice bearing Meth A sarcoma, and tumor regression and survival time were monitored after irradiation with laser light. Tumor regression and complete curing of tumor (80% cure rate by the treatment with 6 mg/kg BPD-MA) were observed when long circulating liposomalized BPD-MA was injected and laser-irradiated. In contrast, only a 20% cure rate was obtained when the animals were treated with BPD-MA solution or BPD-MA entrapped in conventional liposomes. These results suggest that a long-circulating liposomal formulation of photo-sensitive agents is useful for PDT.

Animals↗

PubMed1997

Pyrrole butyric acid derivatives as inhibitors of steroid 5 alpha-reductase.

A series of pyrrole butyric acid derivatives was synthesized and evaluated for inhibitory activity on human and rat steroid 5 alpha-reductase in vitro and ex vivo. 3-Benzoyl-4-alkylpyrrole-1-butyric acids and 1-methyl-2-alkyl-3-benzoylpyrrole-5-butyric acid derivatives were effective inhibitors. Structure activity relationships were evaluated among the 37 compounds synthesized. Compound 37 (HQL-1069) shows potent inhibitory activities against both rat and human 5 alpha-reductase.

5-alpha Reductase Inhibitors↗

PubMed1997

Total synthesis of WS9326A, a potent tachykinin antagonist from Streptomyces violaceoniger.

Total synthesis of the cyclic peptide lactone WS9326A, a potent tachykinin antagonist isolated from Streptomyces violaceoniger strain 9326, has been achieved via Cbz-Thr(Boc-allo-Thr-Asn-Ser(Bzl)-(E)delta MeTyr-Leu-D-Phe-OTce, which was cyclized (Phe and allo-Thr) using an active ester method with N-hydroxysuccinimide. Finally the unique N-acyl group, the 2-(1(Z)-pentenyl)cinnamoyl moiety, was introduced onto the amino group in the Thr unit. The key step of the synthesis involves the preparation of the E-isomer of the dehydro-N-methyltyrosine (delta MeTyr) unit. The debenzoxylation reaction of the threo- and erythro-isomer of the beta-benzoxy-N-methyltyrosine derivatives gave exclusively the Z-isomer of Cbz-Thr-delta MeTyr(MOM)-OMe, which was then converted to the desired E-isomer by photochemical isomerization of Cbz-Thr(TBDMS)-(Z)delta MeTyr(MOM)-Leu-D-Phe-OTce at a later step.

Chromatography, High Pressure Liquid↗

PubMed1997

Prediction of outcome of electrical cardioversion by left atrial appendage flow velocities in atrial fibrillation.

We evaluated the usefulness of left atrial appendage (LAA) flow velocity during atrial fibrillation as an objective measure for prediction of the outcome of electrical cardioversion. Left atrial appendage peak velocities were measured by transesophageal echocardiography before cardioversion in 56 patients. Left atrial thrombus was demonstrated in 6 (11%) of these patients. Cardioversion was then performed in the 50 patients who did not have a thrombus and in 1 patient whose left atrial thrombus disappeared after anticoagulant therapy (n = 51). Thirty-eight patients converted to sinus rhythm which remained stable until discharge (initial success group). Of these, long-term (> 6 months) maintenance of sinus rhythm was achieved in 31 patients (82%). Five patients with almost no detectable appendage contractions during atrial fibrillation were classified in the initial failure group. The peak LAA flow velocity was significantly higher in patients with the initial success group compared with the patients in the initial failure group (25.6 +/- 12.0 vs 15.3 +/- 10.7 cm/s, respectively; p < 0.01). Left atrial appendage flow velocity during atrial fibrillation may be useful for identifying candidates for electrical cardioversion.

Adult↗

PubMed1997

Effects of balloon pulmonary valvuloplasty on atrial shunting--a patient with pulmonary valve stenosis and a large secundum atrial septal defect.

Percutaneous balloon valvuloplasty has been established as an effective treatment for pulmonary valve stenosis (PS) in children and adults. However, there are few reports of the use of this technique in patients with other cardiac anomalies. We report the performance of balloon pulmonary valvuloplasty in a 72-year-old woman with a large atrial septal defect (ASD). This patient had a PS with a right ventricular pressure of 108/18 mmHg and a pulmonary arterial pressure of 42/21 mmHg, corresponding to a 66 mmHg pressure gradient. The ASD measured 32 x 27 mm. Balloon pulmonary valvuloplasty reduced the pressure gradient to 5 mmHg immediately after the procedure and to 2 mmHg 40 days after the procedure. The left-to-right shunt ratio was reduced from 17% before to 12% immediately after and to 36% 40 days after the procedure. In contrast, the right-to-left shunt ratio showed a transient increase from 16% before to 28% immediately after the procedure before decreasing to 11% 40 days after the procedure. The arterial blood oxygen tension was 53 Torr before, 46 Torr immediately after and 55 Torr 40 days after the procedure. The grade of heart failure decreased from New York Heart Association class IV before to class II in the chronic stage. These findings indicated that balloon pulmonary valvuloplasty in a patient with ASD transiently increased the right-to-left shunting associated with a decrease in oxygen tension, but that the change in the chronic stage was slight. In our patient with ASD valvuloplasty was useful in relieving the symptoms associated with elevated right ventricular pressure but could not reduce the hypoxemia caused by right-to-left shunting. In conclusion, valvuloplasty in patients with ASD should be considered as a preoperative treatment with the aim of reducing the risk of surgery and to treat symptoms in patients who refuse to undergo surgery.

Aged↗

PubMed1997

Single dose radiocurability of four murine solid tumors and a predictive assay for the curability in situ.

Correlations between radiocurability and kinetic parameters were investigated in four transplantable tumor types in WHT/Ht mice. The radiation dose to achieve 50% tumor control at 120 days after irradiation, i.e., TCD50/120, was 30 Gy for squamous cell carcinoma H, 32 Gy for squamous cell carcinoma NOS, 46 Gy for rhabdomyosarcoma KAS, and 63 Gy for fibrosarcoma YAS. The tumor cell kinetic parameters investigated were specific growth delay, volume doubling time, 125I-iododeoxyuridine (IUdR) uptake rate, and specific cell loss rate. The specific cell loss rate was defined as the ratio of cell loss rate in non-irradiated tumors to the rate in irradiated tumors, and was obtained by measuring the retention rate of radioactivity in the tumors. No correlations were found between specific growth delay, volume doubling time, 125I-IUdR uptake rate, and TCD50. However, the specific cell loss rate correlated with the TCD50. Therefore, the 125I-IUdR labeling method may be useful as an in situ predictive assay for tumor radiocurability.

Animals↗