Biomedical subjects

T Yasuda

Publications and source records attributed to T Yasuda.

At least 91 records · Page 5Linked to original sources

PubMed2000

Recovery of brain dysfunction after methylmercury exposure in rats.

We studied the time course of central nervous system (CNS) involvement after the termination of methylmercury exposure to rats, in order to investigate whether or not the involvement still progresses even after the termination of exposure. Methylmercury chloride (MMC), at a dose of 2 mg/kg/day, was subcutaneously injected for 25 consecutive days in 12 adult male Sprague-Dawley rats. Six of them were sacrificed on the final day of exposure (group A) after completing the observations of behavioral changes and determining the local cerebral glucose utilization (LCGU) as an indicator of cerebral neuronal activities. Histological examinations of the brain and the sciatic nerve were done. The other six rats were further followed up for 90 days after the termination of exposure (group B). In addition, six rats that received physiological saline served as a control. Group A showed a significant reduction of LCGU without any accompanying cerebral histological alterations and a moderate loss of myelinated fibers in the sciatic nerve. Group B showed normal LCGU rates while severe axonal degeneration of the sciatic nerve was found on the final day of the 90-day follow-up period. The present results demonstrate that a transient involvement of the CNS can occur after MMC exposure. In addition, a complete recovery may occur when the process is mild enough not to cause histological alterations. In contrast, the involvement of the peripheral nerve is much more severe than that of the CNS and it was observed to progress even after the cessation of MMC exposure. Therefore, it seems unlikely, at least in rats, that a steadily progressive course occurs in the CNS but not in the peripheral nerves over a long period of time after MMC exposure.

Animals↗

PubMed2000

Chronic effects of methylmercury on the cerebral function in rats.

We studied the effects of the long-term and small-dose administration of methylmercury chloride (MMC) on the cerebral function in rats. MMC, at a dose of 0.7 mg/kg/day, was subcutaneously injected for 85 consecutive days in nine adult male Sprague-Dawley rats. They were then sacrificed on the final day of exposure (MMC group) after both completing observations on behavioral changes and also determining the local cerebral glucose utilization (LCGU) as an indicator of the cerebral neuronal activities. Histological examinations of the brain and the sciatic nerve were also performed. In addition, seven rats who received physiological saline also served as a control. LCGU significantly decreased in the visual cortex, lateral geniculate nucleus and medial geniculate nucleus without any accompanying histological alterations. Severe axonal degeneration of the sciatic nerve was also observed, which corresponded to the previously described crossed leg phenomenon. The present results suggest that the damage to the peripheral nerve was much more severe than that to the brain, which caused behavioral changes. Although no cerebral morphological changes were observed, brain dysfunction showed a selective involvement of the visual and auditory systems. This finding suggests that LCGU is a sensitive method for detecting the subclinical cerebral dysfunction caused by long-term and small-dose MMC intoxication in the rat brain.

Animals↗

PubMed2000

Intra-tumoral injection of doxorubicin (adriamycin) encapsulated in liposome inhibits tumor growth, prolongs survival time and is not associated with local or systemic side effects.

Encapsulation of doxorubicin (Adriamycin) in liposome (LipADM) augments the anti-tumor effects of the drug and reduces side effects such as cardiotoxicity. However, it does not always enhance anti-tumor effects because of entrapment by the reticuloendothelial system. In this study, we investigated the anti-tumor effect of LipADM injected directly into the tumor to augment tumor targeting. LipADM (7.5 mg/kg body weight), the same concentration as free ADM (FADM), was injected percutaneously or i.v. into 7-day-old established Meth-A tumors in mice. Mock liposome was injected percutaneously into tumors of control mice. Mean relative tumor weights of the 5 groups on day 15 were as follows: intra-tumoral injection of LipADM, 2.92 +/- 1.09; intra-tumoral injection of FADM, 6.99 +/- 2.92; i.v. injection of LipADM, 11.07 +/- 7.95; i.v. injection of FADM, 11.80 +/- 6.55; control, 23.94 +/- 9.03. Mean survival times were as follows: intra-tumoral injection of LipADM, 46.2 +/- 11.0 days; FADM, 34.6 +/- 9.6 days; mock control, 30.2 +/- 4.8 days. Histological examination showed no tissue damage at the site of s.c. injection of LipADM. ADM concentrations in tumor tissues after intra-tumoral injection were persistently high in the LipADM-treated group. Our results indicate that direct injection of LipADM into the tumor is therapeutically useful by producing persistently high concentrations of ADM in the target tissue, with few local and systemic side effects.

Animals↗

PubMed2000

Association of DNase I phenotype 2 with colorectal carcinoma risk in Japanese populations.

We have already demonstrated a significant association of deoxyribonuclease I (DNase I; EC3.1.21.1) polymorphism with liver disease and gastric carcinoma. The aim of this study was to determine whether DNase I polymorphism is closely related to the incident of colorectal carcinoma. We have found a close statistical association between colorectal carcinoma and a high frequency of DNase I phenotype 2 in Japanese populations. However, there was no significant difference in the phenotype distribution between a group of patients with benign diseases and controls. These findings suggest that DNase I phenotype 2 may be potentially useful for identifying patients who are at risk of harboring or developing colorectal carcinoma.

Adult↗

PubMed2000

Fast diffusion of H and creation of dangling bonds in hydrogenated amorphous silicon studied by in situ ESR

The interaction of atomic hydrogen with a-Si:H films was studied by means of in situ ESR during H plasma treatment. H diffuses into the a-Si:H film and creates additional Si dangling bonds ( approximately 10(13) cm (-2)). We observed a high diffusion coefficient (>10(-10) cm (2) s (-1)) at the very initial stage of H treatment (<1 s). The resulting additional dangling bonds are spatially distributed ( approximately 100 nm) into the bulk film. The characteristic depth of dangling bond (db) distribution decreases with increasing H treatment temperature. The activated rate constants of db creation and annihilation reactions determine the distribution of additional dangling bonds at different treatment temperatures.

Journal Article↗

PubMed2000

Palladium-catalyzed cyanation of propargylic carbonates with trimethylsilyl cyanide

[reaction: see text]An equimolar mixture of propargylic carbonate (1) and trimethylsilyl cyanide (2) in THF under reflux affords cyanoallene (3) in the presence of a catalytic amount (5 mol %) of Pd(PPh3)4. In the reaction, the trimethylsilyl moiety of 2 effectively traps the leaving group of 1. The use of 2 in excess (6 equiv) provides dicyanated products (7 or 8) in high yields.

Journal Article↗

PubMed2000

Clinical features of hypertrophic cardiomyopathy caused by a Lys183 deletion mutation in the cardiac troponin I gene.

BACKGROUND: Mutations that cause hypertrophic cardiomyopathy (HCM) have been identified in 9 genes that code proteins in the sarcomere. Previous reports have demonstrated that cardiac troponin I (cTnI) gene mutations may account for familial HCM; however, the clinical characteristics and prognosis of patients with HCM caused by cTnI gene mutations are not known. METHODS AND RESULTS: We analyzed cTnI gene mutations in 130 unrelated probands with HCM and their families to clarify the genotype-phenotype correlations. We identified 25 individuals in 7 families with a Lys183 deletion (Lys183 del) mutation in exon 7 of the cTnI gene. The disease penetrance in subjects aged >20 years was 88% by echocardiography and 96% by ECG. Sudden death occurred in 7 individuals of 4 families at any age. Overall, 7 (43.8%) of 16 individuals aged >40 years had left ventricular systolic dysfunction, and 3 (18.8%) displayed dilated cardiomyopathy-like features. Of affected individuals, 4 of 5 individuals aged >40 years followed by echocardiography showed septal thinning and decreased fractional shortening during >5 years of follow-up. CONCLUSIONS: The Lys183 del mutation in the cTnI gene in patients with HCM is associated with variable clinical features and outcomes. HCM caused by the Lys183 del mutation has a significant disease penetrance. This mutation is associated with sudden death at any age and dilated cardiomyopathy-like features in those aged >40 years. However, it remains unclear whether screening of families with HCM for this mutation will be useful in patient management and counseling.

Adolescent↗

PubMed2000

Geranylgeranyl-pyrophosphate, an isoprenoid of mevalonate cascade, is a critical compound for rat primary cultured cortical neurons to protect the cell death induced by 3-hydroxy-3-methylglutaryl-CoA reductase inhibition.

We investigated the role of the intrinsic mevalonate cascade in the neuronal cell death (NCD) induced by the inhibition of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase in rat primary cortical neurons cultured from the brains of 17-d-old fetal SD rats. HMG-CoA reductase inhibitors induced NCD [HMG-CoA reductase inhibitor-induced NCD (H-NCD)] in time- and dose-dependent manners. The apoptotic characteristics were revealed by the formation of the DNA ladder and by the electron microscopical observation. During the progression of H-NCD, p53 was induced followed by the expression of Bax. Although the mevalonate completely inhibited H-NCD, the cholesterol did not. Thus, we examined two major metabolites of mevalonate, geranylgeranyl-pyrophosphate (GGPP) and farnesyl-pyrophosphate (FPP), using a novel liposome system for uptake into the cells. GGPP, not FPP, prohibited H-NCD with inhibition of the induction of p53 and Bax. The inhibition of HMG-CoA reductase decreased the amount of membrane-associated Rho small GTPase families, but not Ras small GTPase, and GGPP restored the blockage by HMG-CoA reductase inhibitor in the translocation or redistribution of Rho small GTPase families to membrane. These data indicated that (1) the inhibition of the intrinsic mevalonate cascade induces the apoptotic NCD with the induction of p53 followed by that of Bax, (2) the inhibition of HMG-CoA reductase concomitantly causes blockage of the translocation or redistribution of Rho small GTPase families, not Ras small GTPase, to membrane, and (3) GGPP, not FPP, is one of the essential metabolites in the mevalonate cascade for protecting neurons from H-NCD.

Animals↗

PubMed2000

Mammalian deoxyribonucleases I are classified into three types: pancreas, parotid, and pancreas-parotid (mixed), based on differences in their tissue concentrations.

Deoxyribonuclease I (DNase I) activities were measured in 14 different tissues from humans and 5 other mammals (bovine, pig, rabbit, rat, and mouse) by using the single radial enzyme diffusion (SRED) method, which is a sensitive and nonradioactive assay for nucleases. The results indicated that these species are classifiable into three groups on the basis of their different tissue distributions of DNase I. In human and pig, the pancreas showed the highest activity of DNase I; in rat and mouse, the parotid glands showed the highest activity; and in bovine and rabbit, both pancreas and parotid glands showed high activity. Therefore we designated human and pig DNase I as pancreas type, rat and mouse DNase I as parotid type, and bovine and rabbit DNase I as pancreas-parotid (or mixed) type. DNase I of the pancreas type was more sensitive to low pH than the other types. DNase I of pancreas type is secreted into the intestinal tract under neutral pH conditions, whereas the other types are secreted from the parotid gland and have to pass through the very acidic conditions in the stomach. Differences in the tissue distribution and acid sensitivity of mammalian DNases I may provide important information about their digestive function from the evolutionary perspective.

Acids↗

PubMed2000

Surgical outcome of cervical expansive laminoplasty in patients with diabetes mellitus.

STUDY DESIGN: The results from cervical laminoplasty in 18 patients with diabetes mellitus were compared with results from the same procedure in 34 nondiabetic patients matched for age, gender, and disease. OBJECTIVE: To analyze the effects of diabetes mellitus on the surgical outcome after cervical laminoplasty. SUMMARY OF BACKGROUND DATA: There have been no reports on the results of cervical laminoplasty patients with diabetes. METHODS: A retrospective analysis of 18 patients with diabetes mellitus who underwent cervical laminoplasty and 34 nondiabetic patients who underwent the same surgical procedure was undertaken. The postoperative score, intra- and postoperative findings, complications, and radiologic factors were compared between the two groups. In the group with diabetes, the correlation between the recovery rate of the Japanese Orthopedic Association score and the factors indicating the severity of diabetes was assessed. RESULTS: There was no statistical difference between the total Japanese Orthopedic Association scores of the two groups. However, the group with diabetes mellitus showed a poor recovery of sensory function of the lower extremities. Three patients in the group with diabetes had superficial wound complication after surgery. In contrast, none of the patients in the control group had a wound problem. Furthermore, a negative correlation was observed between the recovery rate and the preoperative HbA1 level in the group with diabetes. CONCLUSIONS: Although patients with diabetes mellitus who had cervical myelopathy experienced benefits from cervical laminoplasty similar to those of nondiabetic patients, the patients with diabetes were more likely to have wound complication. Furthermore, the negative correlation between the recovery rate and the preoperative HbA1 value might suggest that long-term diabetes control of more than 2 to 3 months before surgery at least is recommended for a favorable surgical outcome.

Aged↗

PubMed2000

Cbl suppresses B cell receptor-mediated phospholipase C (PLC)-gamma2 activation by regulating B cell linker protein-PLC-gamma2 binding.

Accumulating evidence indicates that the Cbl protein plays a negative role in immune receptor signaling; however, the mode of Cbl action in B cell receptor (BCR) signaling still remains unclear. DT40 B cells deficient in Cbl showed enhanced BCR-mediated phospholipase C (PLC)-gamma2 activation, thereby leading to increased apoptosis. A possible explanation for the involvement of Cbl in PLC-gamma2 activation was provided by findings that Cbl interacts via its Src homology 2 (SH2) domain with B cell linker protein (BLNK) after BCR ligation. BLNK is a critical adaptor molecule for PLC-gamma2 tyrosine phosphorylation through its binding to the PLC-gamma2 SH2 domains. As a consequence of the interaction between Cbl and BLNK, the BCR-induced recruitment of PLC-gamma2 to BLNK and the subsequent PLC-gamma2 tyrosine phosphorylation were inhibited. Thus, our data suggest that Cbl negatively regulates the PLC-gamma2 pathway by inhibiting the association of PLC-gamma2 with BLNK.

Adaptor Proteins, Signal Transducing↗

PubMed2000

Cerebral atrophy in multiple system atrophy by MRI.

Cranial magnetic resonance images (MRI) of the cerebral areas of 40 patients with multiple system atrophy (MSA) and of 61 age-matched controls were analyzed. The cerebral area of MSA patients was 131. 95+/-15.89 cm(2) (mean+/-S.D.), which was significantly smaller than that of normal controls at 149.01+/-10.93 cm(2) (P<0.0001). All 23 MSA cases subjected to the MRI study over a 1-year period showed progressive cerebral atrophy, and the atrophy rate was 2.46+/-1. 66%/year. There were no significant differences within the MSA subtypes or between gender. The progression of cerebral atrophy in MSA correlated more with duration (r=-0.634) than age (r=-0.421). We conclude that MRI findings throughout the course of MSA suggest progressive cerebral atrophy, which is common in all subtypes and reflects duration of the disease rather than age.

Aged↗

PubMed2000

The molecular basis for genetic polymorphism of human deoxyribonuclease II (DNase II): a single nucleotide substitution in the promoter region of human DNase II changes the promoter activity.

Deoxyribonuclease II (DNase II) levels in human vary depending on whether the individual has the DNASE2*H (high) allele or the DNASE2*L (low) allele. We examined the promoter activity of the 5'-flanking region of each of these alleles by transient transfection luciferase assay. DNASE2*H had 5-fold higher promoter activity than DNASE2*L in human hepatoma HepG2 cell. Comparison of the nucleotide sequences of the proximal promoter regions revealed a G to A transition at position -75; G and A residues were assigned to DNASE2*H and *L, respectively. Since no differences were found between the open reading frame sequences of these alleles, it is likely that the A-75G transition causes the allelic difference in the promoter activity of the gene, underlying the genetic polymorphism.

Alleles↗

PubMed2000

Age-related changes of gene expression in mouse kidney: fluorescence differential display--PCR analyses.

We used a fluorescence differential display--PCR (FDD-PCR) technique to analyze the genes expressed in mouse kidneys collected at nine different developmental stages ranging from 3 days to 15 months after birth. We found ten genes that were age-dependent and differentially-expressed in the kidneys during our experimental period. We confirmed by comparative RT-PCR that of the ten cDNAs, seven showed reproducible age-dependent expression. Four of the nucleotide sequences of these cDNA clones, had high homology with known genes (fibronectin, soluble guanylyl cyclase alpha-1 subunit, cytosolic aldehyde dehydrogenase and mitochondrial DNA), and three with expressed sequence tags of unknown genes. The FDD-PCR method was very useful for detecting new age-related genes expressed differentially in the mouse kidney.

Aging↗

PubMed2000

Cardiac sympathetic activity in the asymmetrically hypertrophied septum in patients with hypertension or hypertrophic cardiomyopathy.

BACKGROUND: In patients with essential hypertension (HT), proportional (symmetric) left ventricular hypertrophy (LVH) is common. In contrast, hypertrophic cardiomyopathy (HCM) is characterized by disproportional LVH and, in particular, asymmetric septal hypertrophy (ASH); however, some hypertensive patients also develop ASH. It has not been determined whether such cases represent a distinct type of hypertensive LVH or HCM combined with hypertension. HYPOTHESIS: The study was undertaken to evaluate sympathetic activity in the interventricular septum in patients with HT and ASH or in patients with HCM. METHODS: The patients were evaluated by I-123 meta-iodobenzylguanidine (MIBG) and thallium-201 (201Tl) single-photon emission computed tomography (SPECT), respectively. They were divided into three groups: patients with essential HT and symmetric septal hypertrophy (Group A), patients with HT and ASH (Group B), and patients with HCM and ASH (Group C). RESULTS: Compared with the lateral wall, early uptake of MIBG in the septum was significantly higher in Group B than in Group A, but not significantly different between Groups A and C. Compared with the lateral wall, early uptake of 201Tl in the septum did not differ among the three groups. No significant difference in the MIBG clearance in the lateral wall was seen among the three groups. By contrast, MIBG clearances in the septum and apex were significantly greater in Group C than in Groups A and B. There was an inverse correlation between systolic thickening and MIBG clearance in the septum. CONCLUSION: These findings suggest that sympathetic activity in the septum differs between patients with HT and ASH and patients with HCM.

3-Iodobenzylguanidine↗

PubMed2000

Cementless cup supporter for protrusio acetabuli in patients with rheumatoid arthritis.

The MC cup supporter is an acetabular reinforcement ring for the Harris-Galante (HG) cementless porous-coated socket. This supporting ring has been used with autogenous bone graft since 1991 in the management of protrusio acetabuli in patients with rheumatoid arthritis (RA). We have reviewed 15 hips in 13 patients at an average of 53.6 months (range 24-84 months) after operation. The clinical results of total hip arthroplasty (THA) in protrusio acetabuli using this ring were satisfactory. All grafts appeared to have united radiologically with no radiolucent lines between graft and acetabulum.

Acetabulum↗

PubMed2000

Genomic organization and mapping of mouse CDV (carnitine deficiency-associated gene expressed in ventricle)-1 and its related CDV-1R gene.

We have previously reported that CDV (carnitine deficiency-associated gene expressed in ventricle)-1 was a downregulated gene in the hypertrophied ventricle of carnitine-deficient juvenile visceral steatosis mice and that the related gene (CDV-1R) showed no tissue specificity and no sensitivity to carnitine deficiency. In the present paper, the CDV-1/1R gene was isolated from a mouse genomic BAC library, and the genomic structure was characterized. We found that the CDV-1/1R gene consisted of at least 19 exons and encompassed approximately 48 kb. The splice sites conformed to the GT-AG rule, and the CDV-1R mRNA containing 19 exons was processed. CDV-1 mRNA containing 5 exons was constructed from the 3' half of CDV-1R. The first exon of CDV-1 consisted of the 3' side (116 bp) of intron 14 and exon 15 (87 bp) of CDV-1R. The presumed promoter sequence for CDV-1 located in the intron 14 of CDV-1R contained the common TATA box and consensus binding sites for various transcription factors (Nkx-2.5, Spl, C/EBP, SRF, YY1, and CREB), which seem to play roles in the heart-specific expression and carnitine deficiency-associated suppression of CDV-1. In the upstream region of the CDV-1 promoter, we found two VNTRs, 13 repeats of GATA1, and 16 copies of STRE involved in yeast stress response. The CDV-1/1R gene was located close to DSMIT68 on mouse Chromosome (Chr) 5, corresponding to human Chr 12q24. All these data revealed that two mRNA species, CDV-1 and CDV-1R, are expressed tissue-specifically by using promoters peculiar to each transcript in a single gene.

Animals↗

PubMed2000

Postmortem absorption of dichloromethane: a case study and animal experiments.

A case of accidental death after occupational exposure to an atmosphere containing dichloromethane (DCM) is reported. The concentrations of DCM in the blood and tissues of a 40-year-old man who died while observing an industrial washing machine filled with DCM vapour were blood 1660 mg/l, urine 247 mg/l, brain 87 mg/kg, heart muscle 199 mg/kg and lungs 103 mg/kg which are 3-7 times higher than previously reported fatal levels. The body was left undiscovered in the machine filled with DCM vapour for about 20 h. The present study was designed to determine whether all the DCM detected in the tissues and body fluids had been inhaled while alive using rats as the experimental model. The concentrations of DCM in the tissues and body fluids of a rat that died from DCM poisoning and was left for 20 h in a box containing DCM vapour were the same as those in the tissues and body fluids of a rat that had died from an injected overdose of barbiturates and had then been placed in the DCM box in a similar manner. Moreover, the concentrations of DCM in the tissues and body fluids of the carcasses that were exposed to the DCM vapour increased gradually throughout the period of exposure. These findings imply that DCM is able to penetrate the tissues and body fluids of rat carcasses through a route other than inhalation such as through the skin.

Adult↗