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Biomedical subjects

T Yagi

Publications and source records attributed to T Yagi.

At least 361 records · Page 20Linked to original sources

Reduced spontaneous activity of mice defective in the epsilon 4 subunit of the NMDA receptor channel.

In an attempt to examine the functional significance of the molecular diversity of the N-methyl-D-aspartate (NMDA) receptor channel, we generated mutant mice defective in the epsilon 4 subunit by gene targeting technique. The epsilon 4 subunit mutant mice grew and mated normally. No epsilon 4 subunit protein was detected in the homozygous mutant mice, and the amount of the epsilon 4 subunit protein of 155 kDa was reduced in the heterozygous mice. The expressions of the other NMDA receptor channel subunit mRNAs were not appreciably affected by the mutation. The mutant mice exhibited no obvious histological abnormalities in the various brain regions and in the formation of whisker-related neuronal patterns (barrels, barreloids and barrelettes). In an open field test, however, the epsilon 4 subunit mutant mice showed a reduced spontaneous activity. No significant difference was found between the heterozygous and mutant mice in motor activity and anxiety tests. These results suggest that the epsilon 4 subunit of the NMDA receptor channel plays a role in vivo in controlling the spontaneous behavioral activity.

Analysis of Variance↗

Hepatectomy under extracorporeal circulation.

BACKGROUND: Resection of hepatic tumors located near the confluence of the hepatic vein or invading the inferior vena cava has become technically feasible and relatively safe by using venovenous bypass. However, some technical problems remain to be solved. METHODS: We performed three cases of hepatic resection under extracorporeal circulation combined with hypothermic perfusion. RESULTS: An unexpected hemorrhage was observed in all three cases for different causes. The patient of case 2 died of liver failure developed from fatty liver. Bile duct stenosis was observed in cases 1 and 3. CONCLUSIONS: Although hepatectomy under total vascular exclusion by use of Biopump is now considered a safe procedure, attention should be paid when this procedure is performed because some technical problems still remain.

Blood Loss, Surgical↗

Molecular analysis of mutations induced by 2-chloroacetaldehyde, the ultimate carcinogenic form of vinyl chloride, in human cells using shuttle vectors.

Vinyl chloride (VC) is a carcinogen associated with human and animal cancers. The ultimate carcinogenic form of VC, 2-chloroacetaldehyde (CAA), has been suspected to be mutagenic and we confirmed the mutagenicity of CAA using a modified shuttle vector plasmid. Base sequence analyses of 109 mutant plasmids with mutations in the supF gene, which were treated with CAA and propagated in the cultured human cells, revealed that more than half of the single base substitutions were G:C to A:T transitions with eight hotspots. The majority of the mutations involving G:C base pairs were in 5'-AAGG-3' or 5'-CCTT-3' sequences suggesting that these sequences are the main targets of mutagenesis caused by CAA.

Acetaldehyde↗

Correlation of (6-4)photoproduct formation with transforming mutations in UV-irradiated Ha-ras.

Sites and types of mutations in relation to the amount of cyclobutane pyrimidine dimers (CPDs) and (6-4)-photoproducts in UV-irradiated normal Ha-ras sequences were investigated. Mouse BALB/C 3T3 cells were transfected with UV-irradiated pYN-mHras plasmids containing mouse normal Ha-ras sequences, and transformed foci developed. Direct DNA sequencing of the Ha-ras retrieved from the foci revealed that most mutations (23/24, 96%) took place at dipyrimidine sequences, and the C-->T transition at the 3'-cytosine in 5'-TC or 5'-CC sequences was predominant (17/24, 71%) in codons 12, 13 and 60. In codon 61, where 5'-TC or 5'-CC is absent, two mutations were found at the 5'-TT sequence. More (6-4)photoproducts were produced than CPDs in codons 12, 13 and 60, and more CPDs were produced than (6-4)photoproducts in codon 61. These results suggest that (6-4)photoproducts are the major lesion leading to the mutations in the mouse Ha-ras sequence and subsequent transformation of BALB/C 3T3 cells.

3T3 Cells↗

High prevalence of mutations in the p53 gene in poorly differentiated squamous cell carcinomas in xeroderma pigmentosum patients.

Mutations in the p53 gene were analyzed in 23 squamous cell carcinomas (SCCs) and five basal cell carcinomas from 10 xeroderma pigmentosum patients in Tunisia. Fourteen mutations were detected. Most occurred at the dipyrimidine sequences of DNA, suggesting that they were caused by ultraviolet light. A strong correlation was noted between the presence of the p53 mutations and clinical characteristics such as histology and growth of SCC. In well-differentiated grade 1 SCCs, three (27.3%) of 11 tumors had the p53 gene mutations, whereas in grade 2 and grade 3 SCCs, six (85.7%) of seven tumors had the p53 gene mutations (p < 0.05). Tumors less than 8.0 mm in diameter showed a relatively low frequency of mutation (two of 10 tumors, 20.0%), whereas most of the tumors larger than 8.1 mm (seven of eight tumors, 87.5%) had mutations of the p53 gene (p < 0.025). Multiple tumors in the same xeroderma pigmentosum patients also showed this relation. These results suggest that mutations in the p53 gene lead to the invasive and rapid-growing character of SCC.

Adolescent↗

Three-component analysis of benign paroxysmal positional nystagmus.

Three-component analysis of Benign Paroxysmal Positional Nystagmus (BPPN), focusing on the horizontal, vertical, and torsional, using a computerized eye movement analysis system, was carried out in 10 patients. Using a pendular rotation stimulus, we also measured three components of eye movement elicited from the vertical semicircular canals in normal subjects. We compared two components (vertical and torsional) of BPPN with that of eye movements elicited from the vertical semicircular canals. In BPPN, the torsional component of eye movements was larger than that of the vertical component. Conversely, the vertical component from the vertical semicircular canals was larger than that of the torsional component. From these results, by analysing the vestibulo-ocular reflex of the vertical semicircular canals, it is difficult to support the idea that the pathology of the BPPV is localized in the posterior semi-circular canal alone.

Electronic Data Processing↗

Inner ear autoantibodies in patients with sensorineural hearing loss.

In order to identify the inner ear autoantibodies, sera of 195 patients with sensorineural hearing loss and/or vertigo were reached with bovine inner ear antigen by western blotting method. Positive reaction was seen at several molecular weights, in which 33-35 kD, 42 kD and 68 kD were highly reactive. In moderate to severe hearing loss patients, positive reactions with 33-35 kD, 42 kD, 68 kD and others were 25.8%, 26.8%, 26.8% and 71.5% respectively. On the other hand, a positive rate did not clearly correlate with diagnostic entities. Further study to purify inner ear antigen may evaluate inner ear autoimmune disease.

Animals↗

Nystagmus in benign paroxysmal positional vertigo: a three-component analysis.

Three-component analysis of nystagmus was carried out in 10 patients with benign paroxysmal positional vertigo (BPPV), focusing on the horizontal, vertical and torsional components, with the aid of a computerized eye movement analysis system. Using a pendular rotation stimulus we also measured three eye components of eye movement evoked from the vertical semicircular canals in 3 normal subject; two components (vertical and torsional) of nystagmus in patients with BPPV were compared with that of eye movements derived from the vertical semicircular canals. The time course of slow phase velocity of three components in BPPV patients was similar. In BPPV, the torsional component of eye movements was larger than that of the vertical component without obvious horizontal eye deviation. On the other hand, the vertical component from vertical semicircular canals was larger than that of the torsional component. From the view point of the vestibulo-ocular reflex, it is difficult to support the idea that the pathology of BPPV is localized only to the posterior semicircular canal.

Electronystagmography↗

Extracorporeal circulation and hypothermic perfusion for caval tumor thrombus complicating hepatocellular carcinoma: a case report.

A tumor thrombus complicating hepatocellular carcinoma developed in a 61-year-old male patient. Embolization of the right branch of portal vein was performed 2 weeks before operation. Curative resection of the tumor was performed on by extended hepatectomy plus in situ hypothermic perfusion of the liver and extracorporeal circulation. Postoperative course was uneventful until bile leakage occurred on the 11th postoperative day. A bile duct stenosis was diagnosed by cholangiogram, and hepaticojejunostomy was carried out. The patient recovered well without further complications. The pitfalls and technical problems encountered in this case are herein discussed.

Carcinoma, Hepatocellular↗

[Two cases of intrapulmonary lymph node associated with either progressive systemic sclerosis or idiopathic pulmonary fibrosis].

We encountered 2 cases of intrapulmonary lymph node. Case 1 was in a 48-year-old woman who had been given a diagnosis of progressive systemic sclerosis. Case 2 was in a 49-year-old woman with idiopathic pulmonary fibrosis. In each patient, a follow-up chest CT scan showed a pulmonary nodule, which could not be seen on chest X-ray film. Each nodule has an irregular margin and a linear shadow resembling pleural indentation. Histological examination of the open biopsy specimens revealed that these nodules were intrapulmonary lymph nodes surrounded by interstitial pneumonia. Previous case reports and these 2 cases indicate that unless a thoracotomy is done intrapulmonary lymph nodes are difficult to distinguish from lung cancers.

Diagnosis, Differential↗

[Generation of tumor necrosis factor alpha by human nasal epithelial cells and inhibition by fluticasone propionate].

Accumulation of mast cells and eosinophils in the nasal epithelial layer occurs in nasal allergic reaction, However, the mechanism of accumulation of these cells has not yet been well clarified. We hypothesized that cytokines generated from the nasal epithelial cells contributed to the accumulation of these cells in the nasal epithelial layer. Recently tumor necrosis factor (TNF) was shown to promote polymorphonuclear neutrophils and eosinophils migration. And also TNF increased eosinophil binding to vascular endothelial cells. In this in vitro study we examined whether or not nasal epithelial cells can produce TNF-alpha and also whether or not glucocorticosteroid fluticasone propionate (FP) can modulate TNF-alpha production from nasal epithelial cells. Nasal epithelial cells constitutively produce TNF-alpha in accordance with the nasal epithelial cells' number and this was substantially increased in the state of nasal epithelial cell's proliferating. FP significantly reduced the level of TNF-alpha in the supernatant of cultured nasal epithelial cells for a period of 6 days. In addition, preincubation of nasal epithelial cells with FP for 6 days caused significant reduction of TNF-alpha level in the supernatant of cultured nasal epithelial cells during a further period of 6 days without FP. These data support the concept that structural cells play an active role in the control of allergic and related inflammatory processes.

Adult↗

Insulin resistance and growth retardation in mice lacking insulin receptor substrate-1.

Insulin receptor substrate-1 (IRS-1) is the major substrate of insulin receptor and IGF-1 receptor tyrosine kinases; it has an apparent relative molecular mass of 160-190,000 (M(r), 160-190K) on SDS polyacrylamide gel. Tyrosine-phosphorylated IRS-1 binds the 85K subunit of phosphatidylinositol 3-kinase which may be involved in the translocation of glucose transporters and the abundant src homology protein (ASH)/Grb2 which may be involved in activation of p21ras and MAP kinase cascade. IRS-1 also has binding sites for Syp and Nck and other src homology 2 (SH2) signalling molecules. To clarify the physiological roles of IRS-1 in vivo, we made mice with a targeted disruption of the IRS-1 gene locus. Mice homozygous for targeted disruption of the IRS-1 gene were born alive but were retarded in embryonal and postnatal growth. They also had resistance to the glucose-lowering effects of insulin, IGF-1 and IGF-2. These data suggest the existence of both IRS-1-dependent and IRS-1-independent pathways for signal transduction of insulin and IGFs.

Animals↗

Identification of amino acid residues associated with the [2Fe-2S] cluster of the 25 kDa (NQO2) subunit of the proton-translocating NADH-quinone oxidoreductase of Paracoccus denitrificans.

In order to identify the ligand residues of the [2Fe-2S] cluster of the 25 kDa (NQO2) subunit of the proton-translocating NADH-quinone oxidoreductase of Paracoccus denitrificans, we mutated individually all seven cysteine residues (C61, C96, C101, C104, C113, C137, and C141) and one conserved histidine residue (H92) to Ser or Ala and expressed them in E. coli. After purification of the mutated 25 kDa subunits, the effect of mutations on the iron-sulfur cluster were characterized by chemical analyses and UV-visible and EPR spectroscopy. All mutated subunits, especially mutants of conserved cysteines, contained lower amounts of non-heme iron than wild-type. The subunits of three non-conserved cysteine residues (C61, C104, and C113) mutated to Ser and a histidine residue (H92) mutated to Ala exhibited essentially the same spectroscopic properties as those of the wild-type subunit. In contrast, mutation of the four conserved cysteine residues (C96, C101, C137, and C141) to Ser or Ala considerably altered the UV-visible and EPR spectra from the wild-type subunit. These results indicate that the four conserved cysteine residues coordinate the [2Fe-2S] cluster in the P. denitrificans 25 kDa subunit.

Amino Acids↗

Effect of ethoxyformic anhydride on the Rieske iron-sulfur protein of bovine heart ubiquinol: cytochrome c oxidoreductase.

Treatment of bovine heart ubiquinol-cytochrome c oxidoreductase (complex III, bc1 complex) with ethoxyformic anhydride (EFA) inhibits electron transfer between cytochromes b and c1 [Yagi et al., Biochemistry 21 (1982) 4777-4782]. This paper shows that EFA alters the EPR lineshape of the Rieske iron-sulfur cluster in complex III and in the isolated Rieske protein without a significant decrease of spin concentration. The effect of EFA on the Rieske iron-sulfur cluster is competitive with that of Qo site inhibitors, such as stigmatellin, and is completely reversed by hydroxylamine. These results are consistent with the possible ethoxyformylation by EFA of histidine ligands of the Rieske iron-sulfur cluster at the non-iron binding imidazole nitrogens.

Animals↗