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Biomedical subjects

T Miyajima

Publications and source records attributed to T Miyajima.

At least 37 records · Page 2Linked to original sources

[Utility and intricacy of molecular diagnosis of spinal muscular atrophy].

To diagnose spinal muscular atrophy (SMA), we examined the deletion of exons 7 and 8 of the survival motor neuron (SMN) gene and exon 5 of the neuronal apoptosis inhibitory protein (NAIP) gene in 7 patients from 6 unrelated families, using the polymerase chain reaction method. Two patients with type I and two with type II SMA had the deletion in SMN, whereas 2 of the 3 patients with type III had no deletion in these genes. Thus, the method was not as useful in type III as in type I and II for making a diagnosis of SMA. Together with the data previously reported by others, our data indicated the possibility that the deletion frequency in type III SMA is lower in Japanese patients (< 40%) than in non-Japanese patients (> 80%). Two siblings had SMA of different severity; the older brother having type III and the younger brother type II. Both had the same deletion in the SMN gene. The different phenotypes in these siblings with the same genotype indicated that caution is required when utilizing molecular data for genetic counseling or prenatal diagnosis of SMA.

Child↗

Inhibition of NF-kappaB, iNOS mRNA, COX2 mRNA, and COX catalytic activity by phenyl-N-tert-butylnitrone (PBN).

Previously, the spin trapping agent phenyl-N-tert-butylnitrone (PBN) has been shown to decrease the level of nitric oxide synthase mRNA in vivo. This inhibition is suggested to be an underlying mechanism for PBN's wide variety of pharmacological actions in animal models. However, the determination of PBN's cellular pharmacological activities has not been carried out, but is necessary for the understanding of the effects in vivo. Since the known pharmacological effects of PBN are primarily anti-inflammatory in nature, in this study we determined the inhibitory activities of PBN against two inflammatory factors: inducible nitric oxide synthase (iNOS) and inducible cyclooxygenase (COX2). We show here that PBN decreases steady state COX2 mRNA level and COX2 catalytic activity in macrophage cell culture at supra-pharmacological concentrations. While PBN decreases iNOS mRNA, it does not inhibit iNOS catalytic activity, which is consistent with previous in vivo studies. We also studied nuclear factor kappaB (NF-kappaB), a transcription factor that can rapidly activate the expression of genes involved in inflammatory, immune and acute phase responses. The binding of NF-kappaB to iNOS gene has been shown to be critical for iNOS gene expression, and the promoter region of COX2 gene contains NF-kappaB consensus sequence. We show that PBN inhibits lipopolysaccharide-mediated increase of NF-kappaB DNA binding activity with a lower concentration than that for the non-steroidal anti-inflammatory drug (NSAID), salicylate. Furthermore, we show that PBN inhibits COX2 catalytic activity, suggesting that PBN has an NSAID-like function.

Animals↗

Usefulness of nested PCR and sequence analysis in a nosocomial outbreak of neonatal enterovirus infection.

BACKGROUND: Non-polio enterovirus infections are recognized in children during summer-fall seasons and they sometimes cause large outbreaks. We experienced a nosocomial infection in the neonatal nursery and echovirus type 7 was isolated from samples of four patients. OBJECTIVES: We diagnosed the horizontal infection of four neonates by reverse transcriptase-nested polymerase chain reaction (RT-nested PCR) and the nucleotide sequence. STUDY DESIGN: Total RNA was extracted from clinical isolates, serum samples and cerebrospinal fluid (CSF). We amplified enterovirus genome in the 5'-noncoding region by nested PCR and determined the nucleotide sequences. RESULTS: Enterovirus genome was detected in all isolates, in the acute-phase sera in all four patients and in the CSF in one patient by the first PCR. By using nested PCR, the genome was detected from convalescent-phase sera in two patients. All enterovirus genome obtained from the nursery outbreak showed the same sequences with 100% homology. CONCLUSION: We demonstrated the clinical advantages of RT-nested PCR from serum samples and the analysis of nucleotide sequencing gave the supportive evidence of identification of transmission pathway.

5' Untranslated Regions↗

Nephrogenic diabetes insipidus and tethered cord syndrome with a lipoma of the cauda equina.

The tethered cord syndrome is characterized by sensory and motor disturbances of the lower extremities and incontinence. We report a 12-year-old girl with a cauda equina lipoma and a tethered spinal cord, whose chief complaints were polyuria and polydipsia. She was diagnosed as having nephrogenic diabetes insipidus. This unusual complication of the tethered cord syndrome was most likely due to a hydronephrosis secondary to a neurogenic bladder. Thus, spinal lesions have to be considered in patients with polyuria and polydipsia.

Cauda Equina↗

Comparative electrophysiologic findings between responders and nonresponders to class III antiarrhythmic drugs among patients with ventricular tachyarrhythmia.

Electrophysiologic testing was performed in 31 patients with ventricular tachycardia (21 cases) and fibrillation (10 cases) to characterize the electrophysiologic properties of patients responding or not responding to therapy with class III antiarrhythmic drugs. At the baseline, there were no differences among the patients in the monomorphic VT cycle length (CL), block CL or the width of the zone of entrainment. Ventricular tachyarrhythmias after the administration of class III drugs (sotalol: 9, amiodarone: 15 and E-4031/MS-551: 7) were inducible (non-responders) in 17 patients and non-inducible (responders) in 14 (45%). The class III drugs prolonged the sinus cycle length (SCL), QT interval and right ventricular effective refractory period (VERP), but had little effect on ventricular conduction time in the responders and non-responders. The SCL, QT interval and VERP at the three drive cycle lengths of 600, 400 and 300 msec were significantly longer in the responders than in the non-responders, but the class III drug action on VERP showed a reverse use-dependency. Isoproterenol administered to the responder did not fully reverse the class III antiarrhythmic drug-induced prolongation of QT, QTc and VERP, which remained significantly prolonged compared to the baseline values. Furthermore, when the VERP after the administration of class III drugs were greater than 270, 250 and 240 msec at the three drive cycle lengths of 600, 400 and 300 msec, respectively, it was associated with the non-inducibility of VT/VF. Though the precise mechanism of the drug efficacy is not yet known, these observations help to clarify the ability of class III drugs to prevent the induction of ventricular tachyarrhythmia.

Adult↗

[A case of multiple sclerosis with initial symptoms of narcolepsy].

We reported a 13-year-old boy diagnosed as multiple sclerosis associated with narcolepsy. He had suffered from retrobulbar optic neuritis at the age of 11 years which was improved gradually by prednisolone. Four months later he was admitted because of excessive somnolence. The diagnosis of narcolepsy was made based on hypnagogic hallucination, sleep paralysis, changes of personality and the sleep onset sREM (SOREM). The elevation of anti-measles antibody and a positive oligoclonal band in CSF, low density areas in the bilateral internal capsule on CT scan, and high signal areas in the same region on T2-weighted MRI confirmed the diagnosis of multiple sclerosis. An abnormal arousal response occurred occasionally in sleep stage 2 and 4, which started with electrical silence followed by a period with irregular high voltage slow waves and repetitive focal spike train. Those clinical symptoms and abnormalities of biochemical and electrophysiological studies normalized after treatment with prednisolone. However, abnormalities on MRI showed no improvement even after long term administration of prednisolone (2.5 mg/day).

Adolescent↗

[Donor leukocyte transfusion as treatment for relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation].

Three patients with relapse (two molecular and one cytogenetic relapse) after allogeneic bone marrow transplantation (BMT) for chronic myelogenous leukemia (CML) were treated with donor leukocyte transfusion (DLT). Two had complete molecular remission, which persisted 16 and 20 months after treatment. The performance status of all patients was 90-100%. Mild chronic GVHD was observed in one patient as a side effect of DLT. One patient with cytogenetic relapse required three infusions to attain molecular remission and this suggests the importance of cell numbers to infuse in DLT. Positive anti-nuclear antibody was observed in the effective cases and elevation of IgE in all cases after DLT. These abnormal laboratory findings may suggest a relationship between GVHD and GVL. DLT may be effective therapy for patients with CML who relapse after BMT. Further controlled studies are necessary to determine the optimal number of cells to infuse, interval and frequency of DLT.

Adult↗

[Pulmonary function at the early stage after bone marrow transplantation].

Twenty-one patients, aged 16-41 years, were prospectively followed for pulmonary function prior to and up to nine months after bone marrow transplantation (BMT). All patients had normal radiographs and no clinical signs of pulmonary disease. The FEV1.0%, V25, and of V50/V25 were within the normal ranges for all patients. Percent vital capacity (%VC) and percent diffusing capacity of lung for CO (% DLco) dropped progressively in most of the patients up to 9 months following BMT. Pulmonary function decreased earlier in patients with GVHD as well as patients who received total body irradiation either at a high dose rate (10 cGy/min) or a high lung dose (12 Gy). These asymptomatic declines in pulmonary function were measured by frequent tests of lung function.

Adolescent↗

Analysis of Complexation Equilibria of Polyacrylic Acid by a Donnan-Based Concept

Complexation equilibria of uni- and divalent metal ions (Ag+, Ca2+, Cu2+, and Pb2+) with polyacrylic acid (PAA) have been studied at various degrees of dissociation (alpha) of PAA under different sodium salt concentration levels at 25&deg;C. Both pH and pM(MZ+ = Ag+, Ca2+, Cu2+, and Pb2+) of equilibrium mixture solutions of MZ+/PAA/Na+ (excess) have been determined concurrently by a potentiometric titration method. The electrostatic effect inherent in the polyion-metal ion binding equilibria has been evaluated by a Donnan-based concept and is corrected for by the use of a nonideality term of acid dissociation equilibria of the polyacid as a probe. For Ag+-PAA and Ca2+-PAA bindings, only monodentate ligand complexes, (MA)(Z-1), have proven to be formed, whereas for Cu2+ and Pb2+ ion bindings, formation of both monodentate and bidentate ligand complexes have been observed. For both Cu2+-PAA and Pb2+-PAA systems, bidentate carboxylate complex formation is predominant at alpha > ca. 0.3, whereas at alpha < ca. 0.3, formation of monodentate carboxylate complexes becomes appreciable as alpha decreases. Stability constants of these complexes together with the intra-molecular complexation equilibrium constants expressed by the ratio of the concentrations of bidentate complexes to monodentate complexes have successfully been evaluated and are compared with each other in order to discuss the multidentate complexation properties of the polycarboxylic acid.

Journal Article↗

Optimal time and dosage of phenyl N-tert-butyl nitrone (PBN) for the inhibition of nitric oxide synthase induction in mice.

We have previously reported that phenyl N-tert-butyl nitrone (PBN) inhibits the induction of inducible nitric oxide synthase (iNOS) and, thus, prevents the overproduction of nitric oxide (NO), resulting in the reduction of endotoxin-mediated death in mice. In this study, to examine the effect of PBN in detail, we investigated the dose- and administration-timing dependence of PBN on endotoxin-induced NO generation in mice. NO generation was monitored in the mouse liver after administration of lipopolysaccharide (LPS) by the in vivo NO-spin trapping method using the iron complex of N-methyl-D-glucamine dithiocarbamate (MGD) as a spin trap, followed by ex vivo EPR measurement of the liver tissue. PBN was effective in reducing liver NO generation monitored 6 h after endotoxin injection when it was administered shortly before or after LPS injection. The maximum inhibition of liver NO was obtained when PBN was administered 30 min before LPS injection. ID50 for the inhibition was estimated to be approximately 200 mg/kg when the LPS dose of 50 mg/kg was used. Expression of mRNA for iNOS in the liver as estimated by reverse transcription polymerase chain reaction was decreased when PBN was given 30 min before LPS injection, indicating that the reduction of expression of iNOS protein by PBN, which has been shown previously, is at least in part caused by a decrease in mRNA expression.

Animals↗

On the Complexation of Cd(II) Ions with Polyacrylic Acid

Complexation of Cd(II) ions with polyacrylic acid has been studied potentiometrically and by 113Cd NMR spectroscopy. A Donnan model proposed by Marinsky (Marinsky, J. A., in "Ion Exchange and Solvent Extraction" (J. A. Marinsky and Y. Marcus, Eds.), Vol. 11, p. 237. Dekker, New York, 1993; Miyajima, T., in "Ion Exchange and Solvent Extraction" (J. A. Marinsky and Y. Marcus, Eds.), Vol. 12, p. 275. Dekker, New York, 1995) has been applied in order to correct for the electrostatic effect on the equilibria inherent in the polyelectrolyte nature of the polyions. The potentiometric studies showed that the bidentate ligand complex, (CdA2)0, is the dominant species, but the formation of monodentate ligand complex, (CdA)+, cannot be neglected at low degree of dissociation of the polyacid. The stability constants of the (CdA)+ and (CdA2)0 complexes have been determined to be approximately 3.2 x 10 and 1.6 x 10(2), respectively. These values are in good agreement with the stability constants of 4.1 x 10 and 1.0 x 10(2) for Cd(acetate) and Cd(glutarate) complexes, where acetate and glutarate ions are the monomer analog ligands of polyacrylic acid. The 113Cd NMR chemical shift change upon dissociation of the polyacid also indicates that the dominant complex is (CdA2)0, but (CdA)+ becomes more appreciable with the decreasing degree of dissociation of the polyacid.

Journal Article↗

Rebamipide protects against activation of neutrophils by Helicobacter pylori.

Our objectives were to determine whether rebamipide, a unique antiulcer agent, would inhibit adhesive reactions between neutrophils and endothelial cells as well as the production of active oxygen species from neutrophils elicited by an extract of H. pylori. A water extract of H. pylori that was prepared from biopsy materials obtained from a patient with gastric ulcer increased the surface expression of CD18 on human neutrophils isolated from peripheral blood, the adhesion of neutrophil-endothelial cells, and the production of active oxygen species by neutrophils. Rebamipide, at concentrations of 10(-5) and 10(-6) M, reduced the adherence of neutrophils to endothelial cells as well as the CD18 expression on neutrophils induced by this bacterial extract. Rebamipide also inhibited the production of active oxygen species from neutrophils stimulated by H. pylori extract. These results suggest that rebamipide protects against the gastric mucosal inflammation associated with H. pylori by inhibiting neutrophil function.

Alanine↗

Spin trapping agent, phenyl N-tert-butyl nitrone, inhibits induction of nitric oxide synthase in endotoxin-induced shock in mice.

Spin trapping agent, phenyl N-tert-butyl nitrone (PBN) significantly reduces mortality due to lipopolysaccharide (LPS)-induced shock in Balb/c mice as had previously been shown in rats. We hypothesized that PBN decreases mortality by directly or indirectly inhibiting nitric oxide (NO) generation. Therefore, we determined the effect of PBN administration on LPS-induced NO generation in mice. NO generation was monitored in the mouse liver after administration of LPS by an in vivo NO-spin trapping, followed by ex vivo EPR measurement. When the mice was treated with PBN 0.5hr before LPS administration, NO generation in the liver was reduced by 80%. However, when PBN was given 3hrs after LPS, NO generation did not change. Both pre- or post-administration of NO synthase (NOS) inhibitor, NG-monomethyl-L-arginine inhibited the NO generation. Western blotting of inducible NOS (iNOS) in mouse liver cytosol obtained from PBN-pretreated animals demonstrated a decreased expression of iNOS, indicating the reduction in NO generation was caused by the decrease in the amount of enzyme present but not by the inhibition of iNOS enzyme activity per se.

Animals↗

Effects of alcohol moderation on blood pressure and intracellular cations in mild essential hypertension.

It is known that moderation of alcohol intake reduces blood pressure, although the exact mechanism has not yet been established. To clarify the hypotensive mechanism of alcohol reduction, we evaluated the change in cellular magnesium and sodium metabolism during alcohol reduction in mild hypertensive patients. We measured intraerythrocyte sodium and magnesium, intraplatelet free magnesium concentrations, and erythrocyte ouabain-sensitive 22Na efflux rate constant (Kos) in 17 mild essential hypertensive patients regularly consuming more than 40 g/day of alcohol, before and after 4 weeks of alcohol reduction, and 12 age-matched nondrinking hypertensives. Intraerythrocyte magnesium (P < .01) and intraplatelet free magnesium (P < .05) concentrations were significantly lower in drinkers than in nondrinkers. In drinkers, advice to reduce alcohol intake for 4 weeks resulted in a reduction in self-reported alcohol consumption from 461.7 to 71.6 g/week, a significant fall in both supine systolic blood pressure (136.3 +/- 10.8 to 130.8 +/- 11.3 mm Hg, P < .001) and supine diastolic blood pressure (85.1 +/- 8.6 to 82.6 +/- 8.7 mm Hg, P < .05). The fall in mean blood pressure correlated positively with the reduction in weekly alcohol consumption. Intraerythrocyte magnesium and Kos were increased (P < .05, P < .01, respectively), while intraerythrocyte sodium was decreased (P < .01). The increase in intraerythrocyte magnesium correlated negatively with the fall in mean blood pressure and positively with the increase in Kos, which correlated negatively with the decrease in intraerythrocyte sodium.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Alternation of QRS morphology and effect of radiofrequency ablation in idiopathic ventricular tachycardia.

UNLABELLED: We performed electrophysiological studies in 13 patients with idiopathic VT and attempted radiofrequency (RF) catheter ablation in 4 of them. RESULTS: VT was induced by programmed stimulation in all patients and the mean cycle length was 363 +/- 58 msec. In 8 of 13 patients (62%), alternation of either the cycle length and/or morphology of VT was observed. Transient entrainment was achieved in all patients by rapid pacing from the right ventricular outflow tract so reentry was considered the underlying mechanism of VT. The site of earliest activation (EAS) during VT was located at the apicoposterior portion of the left ventricular septum and used as the target site for RF catheter ablation. Spikelike presystolic activity was detected 20-40 msec prior to the large deflection of the local electrogram in four patients. VT was terminated by a few seconds of RF current in all four patients, but subsequently new VTs with a slightly different morphology were induced in three of them and re-mapping showed a shift of the EAS. After additional RF ablation at the new EAS, VT was no longer induced. No complication was noted and VT did not recur during a follow-up period for a mean of 9.3 +/- 5.2 months. CONCLUSION: RF catheter ablation seems useful and safe for idiopathic VT. The alternation of QRS morphology and the findings at the time of catheter ablation suggest that an alternative pathway or multiple exists may be present in some patients with idiopathic VT, because the change in VT morphology was associated with a shift of the EAS.

Adolescent↗

Hepatitis C viral markers in patients who received blood that was positive for hepatitis C virus core antibody, with genetic evidence of hepatitis C virus transmission.

BACKGROUND: Despite the use of the anti-c100-3 assay for blood donor screening, posttransfusion non-A,non-B hepatitis still occurred. A more sensitive assay should be developed to prevent this. STUDY DESIGN AND METHODS: Stored serum specimens from 2020 healthy blood donors who were negative for c100-3 antibody to hepatitis C virus (HCV) were retrospectively screened for the presence of antibodies against a core protein of HCV using an enzyme-linked immunosorbent assay and Western blot analysis as part of a study on posttransfusion non-A,non-B hepatitis. RESULTS: Eight (0.4%) of the 2020 donors were positive for HCV core antibody. Posttransfusion non-A,non-B hepatitis occurred in 5 of five patients known to have received blood that was positive for HCV core antibody and 1 of 141 patients transfused with blood that was negative for HCV core antibody. The total incidence of posttransfusion non-A,non-B hepatitis was 4.1 percent (6/146). The nucleotide sequence of the nonstructural 5 region of the HCV genome obtained from two donors and corresponding recipients was also analyzed. The HCV genome sequences were identical for one donor-recipient pair, and there was 99.4-percent homology for a second pair. CONCLUSION: Anti-core-positive blood proved to be highly infectious for HCV, and this validated the use of the second-generation anti-HCV assay for blood donor screening.

Base Sequence↗

Radiofrequency current catheter ablation for ventricular tachycardia.

UNLABELLED: Radiofrequency current catheter ablation was attempted for 17 morphologies of ventricular tachycardia (VT) in 14 patients. Five patients had underlying heart disease. The site of VT origin was determined as the earliest site of ventricular activation, or by pacing within the area of slow conduction. In 15 VTs, ablation was performed during VT, and 12 VTs (80%) were terminated within an average of 5.4 +/- 4.2 seconds. After ablation, 14 VTs (14/17 = 82%) of 11 patients (11/14 = 79%) could not be induced by electrical stimulation. Radiofrequency ablation appeared to be more effective in VTs without underlying heart disease (91%), and in VTs originating from the right ventricle (100%). Successful ablation sites usually showed a normal local electrograms during VT. Ablation in the slow conduction area was attempted in 3 VTs, and 2 VTs became noninducible. The mean number of applications of radiofrequency current for each VT origin was 7.7 +/- 6.4 at 20-50 Watts. In 4 patients, application of radiofrequency current was required 10 or more times because of a possible large arrhythmogenic area, or because of reinduction of VT, even though VT was terminated by radiofrequency current. No major complication was observed except for complete right bundle branch block in 1 patient. IN CONCLUSION: (1) Radiofrequency catheter ablation was considered to be effective and safe, especially for VT without underlying heart disease or VT originating from the right ventricle. (2) Ablation during VT was considered to be useful for identifying the proper ablation site and to avoid creating an unnecessary lesion.

Adult↗