Biomedical subjects

T Toda

Publications and source records attributed to T Toda.

At least 145 records · Page 8Linked to original sources

PubMed1997

Resistance to diverse drugs and ultraviolet light conferred by overexpression of a novel human 26 S proteasome subunit.

We have investigated the usefulness of the fission yeast Schizosaccharomyces pombe as a model organism for the discovery of novel modes of drug resistance in human cells. In fission yeast, overexpression of the essential pad1(+) gene confers pleiotropic drug resistance through a pathway involving an AP-1 transcription factor encoded by pap1(+). We have identified POH1, a human pad1 homologue that can substitute fully for pad1(+) and induce AP-1-dependent drug resistance in fission yeast. POH1 also confers P-glycoprotein-independent resistance to taxol (paclitaxel), doxorubicin, 7-hydroxystaurosporine, and ultraviolet light when transiently overexpressed in mammalian cells. Poh1 is a previously unidentified component of the human 26 S proteasome, a multiprotein complex that degrades proteins targeted for destruction by the ubiquitin pathway. Hence, Poh1 is part of a conserved mechanism that determines cellular susceptibility to cytotoxic agents, perhaps by influencing the ubiquitin-dependent proteolysis of transcription factors.

Amino Acid Sequence↗

PubMed1997

Fission yeast WD-repeat protein pop1 regulates genome ploidy through ubiquitin-proteasome-mediated degradation of the CDK inhibitor Rum1 and the S-phase initiator Cdc18.

In fission yeast, maintenance of genome ploidy is controlled by at least two mechanisms. One operates through the Cdc2/Cdc13 kinase, which also involves the CDK inhibitor Rum1, and the other through the S-phase regulator Cdc18. By screening for sterile mutants that show increased ploidy, we have identified a new gene, pop1+, in mutants that become polyploid. The pop1 mutation shows a synthetic lethal interaction with the temperature-sensitive cdc2 or cdc13 mutation. In a pop1 mutant Rum1 and Cdc18 proteins become accumulated to high levels. The high ploidy phenotype in the pop1 mutant is dependent on the presence of the rum1+ gene, whereas the accumulation of Cdc18 is independent of Rum1. The predicted sequence of the Pop1 protein indicates that it belongs to a WD-repeat family with highest homology to budding yeast Cdc4, which participates in the ubiquitin-dependent pathway. Consistent with this notion, in a mutant of the 26S proteasome, higher molecular weight forms of Rum1 and Cdc18 are accumulated corresponding to polyubiquitination of these proteins. In the pop1 mutant, however, no ubiquitinated forms of these proteins are detected. Finally we show that Pop1 binds Cdc18 in vivo. We propose that Pop1 functions as a recognition factor for Rum1 and Cdc18, which are subsequently ubiquitinated and targeted to the 26S proteasome for degradation.

Amino Acid Sequence↗

PubMed1997

YAC and cosmid contigs encompassing the Fukuyama-type congenital muscular dystrophy (FCMD) candidate region on 9q31.

Fukuyama-type congenital muscular dystrophy (FCMD), the second most common form of childhood muscular dystrophy in Japan, is an autosomal recessive severe muscular dystrophy associated with an anomaly of the brain. We had mapped the FCMD gene to an approximately 5-cM interval between D9S127 and D9S2111 on 9q31-q33 and had also found evidence for linkage disequilibrium between FCMD and D9S306 in this candidate region. Through further analysis, we have defined another marker, D9S172, which showed stronger linkage disequilibrium than D9S306. A yeast artificial chromosome (YAC) contig spanning 3,5 Mb, which includes this D9S306-D9S172 interval on 9q31, has been constructed by a combination of sequence-tagged site, Alu-PCR, and restriction mapping. Also, cosmid clones subcloned from the YAC were assembled into three contigs, one of which contains D9S2107, which showed the strongest linkage disequilibrium with FCMD. These contigs also allowed us to order the markers as follows: cen-D9S127-(approximately 800 kb)-D9S306 (identical to D9S53)-(approximately 700 kb)-A107XF9-(approximately 500 kb)-D9S172-(approximately 30 kb)-D9S299 (identical to D9S774)-(approximately 120 kb)-WI2269-tel. Thus, we have constructed the first high-resolution physical map of the FCMD candidate region. The YAC and cosmid contigs established here will be a crucial resource for identification of the FCMD gene and other genes in this region.

Chromosomes, Artificial, Yeast↗

PubMed1997

Synchronous multiple colorectal adenocarcinomas.

BACKGROUND: The object of the present work was to characterize clinical features and the quality of preoperative examinations in patients with synchronous colorectal carcinomas, and to compare the incidence of associated benign polyps with our findings in patients with a single malignant lesion. METHODS: A retrospective evaluation of 225 patients with primary colorectal carcinoma revealed 9 cases (4.0%) of synchronous colorectal carcinomas. RESULTS: The synchronous colorectal carcinomas were located in the same anatomical segment in 7 patients and were divided into different segments in 2 patients. The accuracy of preoperative diagnosis was 55.6% by endoscopy alone and 66.7% by double contrast barium enema (DCBE) alone, while the rate was 77.8% when colonoscopy and DCBE were combined. There was a higher incidence of associated benign polyps in the group with synchronous colorectal carcinomas (55.6%) versus 28.7% for a single carcinoma (P < 0.05). The main reason why multiple lesions could not be identified preoperatively was that the distal lesions prevented examination of the proximal lesions. CONCLUSIONS: At the time of surgical resection, it is important to ascertain preoperatively whether or not a second lesion exists. If synchronous polyps are present in patients with synchronous colorectal carcinomas, they should be ablated to reduce the risk of metachronous colorectal carcinoma.

Adenocarcinoma↗

PubMed1997

Ooplasmic round spermatid nuclear injection procedures as an experimental treatment for nonobstructive azoospermia.

PURPOSE: Our objective was to apply ooplasmic round spermatid nuclear injections for the treatment of nonobstructive azoospermia. MATERIALS: Participants were nine azoospermic men who had previously undergone diagnostic testicular biopsy. Spermatogenetic arrest was diagnosed at the round spermatid stage (n = 6) or primary spermatocyte stage (n = 3). A second (therapeutic) testicular biopsy was performed and round spermatid nuclei were recovered from all the participants. RESULTS: Forty-nine mature oocytes were successfully injected with nuclei and then cultured for 72 hr. Twenty-four embryos were transferred to nine women. No pregnancy was achieved. CONCLUSIONS: Round spermatids can be recovered from therapeutic testicular biopsy material of men negative for round spermatids in previous routine diagnostic testicular biopsy specimens. Round spermatid nuclear injections may play a role in the treatment of nonobstructive azoospermia.

Adult↗

PubMed1997

Molecular genetic evidence of clinical heterogeneity in Fukuyama-type congenital muscular dystrophy.

Fukuyama-type congenital muscular dystrophy (FCMD) is an autosomal recessive severe muscular dystrophy associated with brain malformation. The gene responsible for FCMD was mapped to chromosome 9q31, a region in which convincing evidence of strong linkage disequilibrium between FCMD and mfd220 (D9S306) was recently found. FCMD is also characterized clinically by a peak motor function which, at best, allows patients to sit unassisted or slide on the buttocks. However, a small fraction of patients acquire the capacity to walk unassisted. Whether such ambulant cases belong to the FCMD spectrum or to a different disease entity has been a topic of considerable debate. We performed linkage analysis for ten families with ambulant cases using DNA markers flanking the FCMD locus. The mfd220 locus yielded a significant lod score of 3.09 for ambulant FCMD. We also found evidence for linkage disequilibrium between ambulant FCMD and mfd220. We further conducted haplotype analysis in FCMD siblings with different phenotypes, one of whom was ambulant while the other was not. The results indicate that the FCMD siblings share exactly the same haplotype at nine marker loci spanning 23.3 cM surrounding the FCMD locus. On the basis of these results, we conclude that, genetically, ambulant cases are, in fact, part of the FCMD spectrum.

Adolescent↗

PubMed1997

Endoscopic and pathologic features of Epstein-Barr virus-associated gastric carcinoma.

BACKGROUND: Although the presence of Epstein-Barr virus has been documented in approximately 7% of patients with gastric carcinoma, the clinical features of Epstein-Barr virus-associated carcinoma have not been well documented. We studied the histologic and endoscopic characteristics of Epstein-Barr virus-associated gastric carcinoma. METHODS: We tested 124 gastric carcinomas from 117 patients using in situ hybridization for Epstein-Barr virus encoded small RNA1. The histologic and endoscopic findings in the Epstein-Barr virus-associated groups and the negative control groups were analyzed and compared. RESULTS: Twelve tumors (9.7%) were identified as Epstein-Barr virus associated. These lesions were located mainly in the upper part of the stomach (p < .05) and had a diffuse-type histology (p < .05) compared with those in the control group. Six of seven (85.7%) early Epstein-Barr virus-associated lesions were type 0 IIc (superficial depressed) or a combined type, and 42.9% were accompanied by submucosal nodules of carcinoma with lymphoid stroma. Four of five (80%) advanced Epstein-Barr virus-associated tumors were type 3 (ulcerated without definite limits), thought to be the advanced shape of superficial depressed lesions. CONCLUSIONS: Epstein-Barr virus-associated gastric carcinomas often appear as superficial depressed or ulcerated lesions in the upper part of the stomach and have a diffuse-type histology with lymphoid infiltration.

Adult↗

PubMed1997

Histopathological study of a newly developed root canal sealer containing tetracalcium-dicalcium phosphates and 1.0% chondroitin sulfate.

We studied the possibility of the clinical use of a calcium phosphate-type newly developed sealer composed of tetracalcium phosphate, dicalcium phosphate dihydrate, and a modified McIlvain's buffer solution (TDM). Another sealer using the buffer solution, to which 2.5% chondroitin sulfate was added to promote wound healing (TDM-S), was also studied. TDM and TDM-S were histopathologically compared with another type of calcium phosphate sealer (ARS), which is commercially available in Japan, in the dorsal subcutaneous tissue and in the periapical tissue of rats. TDM and TDM-S caused no inflammatory reactions in the subcutaneous tissue. The periapical tissue reacted mildly to them. ARS caused severe inflammatory reactions in both the subcutaneous and the periapical tissue. These results indicate that TDM-S has excellent histocompatibility and potential as a root canal sealer.

Acrylic Resins↗

PubMed1997

Effectiveness of eucalyptol and d-limonene as gutta-percha solvents.

Eucalyptol and d-limonene were evaluated for their ability to serve as a substitute solvent for chloroform. The amount of time required to soften and remove the gutta-percha in 72 instrumented and filled simulated root canals in epoxy blocks was measured. After preparation to the apices of the block canals with a #60 file, four different filling techniques were used. These obturations were softened with each solvent and then removed, first using a #15 Hedstrom file inserted to full working length, and then removing the remaining filling mass with a #60 reamer. The two instrument placements were timed: one for the Hedstrom file insertion to the apex and the other for the reamer to remove the filling material. Neither the different solvents nor the filling techniques had a significant effect on the times required for the H-files to reach the apex. However, the times for the reamer to remove the filling materials were effected both by the filling techniques and the solvents used.

Chloroform↗

PubMed1997

A case report of carotid body tumor.

A case of left carotid body tumor is presented. A 47-year-old female patient consulted our otorhinolaryngological clinic with a neck swelling that had persisted for 5 months. On physical examination, a movable and pulsating hard mass measuring 2 x 2.5 cm in size was found on the left side of her neck, near the angle of the mandible. Computed tomography, magnetic resonance image and angiography all demonstrated a well-circumscribed tumor mass showing high vascularity and located at the bifurcation of the left carotid artery. The tumor involved the left carotid artery, but the patency of the artery was preserved. The patient showed satisfactory temporary balloon occlusion test results without neurological complications. Since the tumor was strongly adherent to the carotid arterial wall, the tumor was resected together with the carotid artery. Histologically, the tumor was composed of organoid clusters of round cells with eosinophilic granular cytoplasm. Involvement of tumor cells was seen to the adventitia of the carotid artery, but only slight cellular atypia was seen. Ultrastructurally, two types of cells were observed in the central and marginal portion of the tumor; these were round chief cells with few cytoplasmic neurosecretory granules and spindle-shaped sustentacular cells. Immunohistochemically, the chief cells and sustentacular cells showed positive reaction for neuron-specific enolase and S-100, respectively. The ultrastructural findings suggested the benign nature of the tumor.

Biomarkers, Tumor↗

PubMed1997

Polymorphism analysis of Fukuyama type congenital muscular dystrophy (FCMD) siblings with different phenotypes.

Peak motor function in Fukuyama type congenital muscular dystrophy (FCMD) is generally considered to be no better than sitting without help or sliding on the buttocks. There are a few patients who acquire the ability to stand and a small fraction of our total congenital muscular dystrophy (CMD) population are able to walk at some point. These ambulant cases may reflect a broad spectrum of motor disabilities in the category of FCMD, or may represent another CMD entity, which closely resembles but is distinct from FCMD. Since the localization of the FCMD gene to chromosome 9q3 1 by Toda et al. in 1993 and 1994, polymorphism analysis of this disease has become possible. We describe correlations between clinical features and genetic analysis using microsatellite markers flanking the FCMD locus in two FCMD families each having two affected children with distinctly different motor abilities. The results demonstrate that two sets of FCMD siblings share exactly the same haplotype at nine marker loci spanning 23.3 cM, surrounding the FCMD locus. Our results provide genetic confirmation that some FCMD cases may acquire the ability to walk.

Adolescent↗

PubMed1997

Strip biopsy to treat esophageal granular cell tumor.

Esophageal granular cell tumors are rare neoplasms. We successfully treated a 35-year-old Japanese man with an esophageal granular cell tumor without any complications using strip biopsy. Endoscopic ultrasonography revealed a hypoechoic tumor with a diameter of 8 mm that was confined to the submucosal layer. A strip biopsy done with a two-channel endoscope completely resected the tumor. Six months later, no abnormal findings were recognized in the resected area. Therefore we propose that strip biopsy be considered as a viable alternative treatment for esophageal granular cell tumor, depending on the histologic character, tumor size, and depth of tumor infiltration.

Adult↗

PubMed1997

Clinicopathologic features of resected primary adenosquamous carcinomas of the liver.

Four cases of resected adenosquamous carcinoma of the liver were clinicopathologically reviewed, together with immunohistochemical findings. Although no lymph node metastases were seen and a curative resection was achieved in all cases, two patients had recurrences in the peritoneum and distant organs such as the pericardium and pleura relatively soon after the operation. Of the remaining two cases, one patient died during the postoperative period and the other died of coexistent hilar cholangiocarcinoma. Together these findings suggest that this disease tends to spread locally and distantly in the early phase of tumor growth and shows aggressive biological behavior. In an immunohistochemical study, involucrin was a specific marker for the squamous component and CA19-9 was a marker for the adenomatous component.

Aged↗

PubMed1997

Apolipoprotein A-1 of Japanese quail: cDNA sequence and modulation of tissue expression by cholesterol feeding.

Apolipoprotein (apo) A-1 cDNA was amplified by the reverse-transcriptase-polymerase chain reaction (RT-PCR). Primers were synthesized according to the nucleotide sequence of chicken apo A-1, and the identity of apo A-1 cDNA was confirmed by comparing with the N-terminal amino acid sequence. The open reading frame of apo A-1 cDNA consists of 795 nucleotides, and it is capable of coding a polypeptide of 264 amino acids. A comparison between quail and chicken apo A-1 revealed 94.5% homology in the nucleotide sequence and 91.7% homology in the amino acid sequence. There was a similar 11- or 22-amino acid repeat in quail apo A-1 as was the case for chicken apo A-1. Apo A-1 mRNA was evaluated to be 1.4 k in length and was expressed in various tissues of Japanese quail: the liver, small intestine, lung, kidney, heart, and muscle. A quantitative evaluation, however, revealed that the liver and small intestine were the major organs for apo A-1 synthesis, accounting for more than 90% of the total expression of apo A-1 mRNA. Besides apo A-1 mRNA (1.4 k in length), a transcript of 4.1 k was detected in all the tissues examined, with a magnitude ranging from 5 to 10% of the apo A-1 mRNA level. The effect of cholesterol level on the expression of apo A-1 mRNA was studied to address the physiological significance of apo A-1 in the liver, small intestine, and muscle. The level of cholesterol in the liver and breast muscle was increased by feeding with cholesterol and reached a saturation level at day 7. There was also a temporal rise of cholesterol level at day 7 in the small intestine. Dietary cholesterol increased the expression of apo A-1 mRNA two fold in both the liver and small intestine. This was not the case for breast muscle, in which the expression of apo A-1 mRNA was not modulated by the cholesterol level.

Amino Acid Sequence↗

PubMed1997

Lipoprotein and apoprotein profiles of hyperlipidemic atherosclerosis-prone Japanese quail.

The purpose of this study was to characterize the lipoprotein and apoprotein profiles of hyperlipidemic atherosclerosis-prone (HAP) Japanese quail. HAP and commercially available (CA) Japanese quail were fed either a semi-purified diet containing 1% cholesterol or a cholesterol-free diet for two weeks. The lipoproteins of CA and HAP quail fed cholesterol-free diet were composed of two fractions: densities ranging from 1.02 to 1.09 and from 1.09 to 1.21. The lipoprotein distribution patterns obtained from both strains showed an HDL-predominant pattern. A protein of 26 kDa was the major apoprotein in the entire density range of the lipoprotein class. Marked increases in the cholesterol ester levels were observed in the lower density fractions (1.006 < d < 1.055: chylomicron and VLDL fractions) of the cholesterol-fed quail, accounting for 46% of the total lipids in CA quail and 54% in HAP quail. In addition, the presence of a protein of 470 kDa was exclusively observed in the lower density fractions (1.006 < d < 1.055) of the cholesterol-fed HAP quail. The fatty-acid compositions of the chylomicron and VLDL fractions were affected by the dietary cholesterol in both strains: a decrease in concentration of 16: 0 and increase in 18: 0 (weight %). However, cholesterol feeding had no effect on the level of cholesterol, chemical composition or fatty-acid composition of the HDL fractions in either strain. Although the lipoprotein and apoprotein profiles of HAP quail showed resemblances to those of the CA quail, expression of the 470 kDa protein in the lipoproteins (d < 1.055) appeared to be pronounced in HAP quail. The relevance of these lipoprotein and apoprotein profiles to the genesis of atherosclerosis was discussed in this study.

Animals↗

PubMed1997

[Indication for percutaneous transluminal coronary angioplasty based on quality of life of patients with angina pectoris].

The changes in quality of life (QOL) before and after percutaneous transluminal coronary angioplasty (PTCA) were investigated to establish criteria for determining whether patients with angina pectoris should undergo PTCA. The QOL was surveyed twice by self-completed questionnaire for QOL by Iida and Kohashi (QUIK) before and about 4 months after PTCA in 84 patients (mean age 62.8 +/- 10.1 years) with angina pectoris. High QUIK score reflects a poor QOL, of which the internal consistency was 0.86, demonstrating high reliability. The subjects were classified into three groups according to the changes of total QUIK score before and after PTCA (I: QOL improved 31.0%, II: QOL unchanged 48.8%, III: QOL worsened 20.2%). Age, gender, total QUIK score prior to PTCA, presence of anginal pain, complications extent and degree of coronary artery stenosis, and left ventricular ejection fraction were compared between the three groups. The total QUIK score prior to PTCA in the improved QOL group was higher than that in the worsened QOL group (11.6 vs 5.1, p < 0.01). Most patients showing a poor QOL prior to PTCA demonstrated an improvement in their QOL after PTCA. The number of patients with anginal pain prior to PTCA was high in the improved QOL group (35.8%, p < 0.05). Percutaneous transluminal coronary angioplasty might not aggravate QOL (12.1%, p = 0.1) in patients with single-vessel disease. In patients with multivessel disease, PTCA might not improve (35.3%) but also might aggravate QOL (25.5%). Multivariate analysis showed that PTCA improved QOL in male or sixty-ager patients and in patients with a total QUIK score of 10 or more prior to PTCA (p < 0.01). The total QUIK score, presence of anginal pain and extent of coronary artery stenosis prior to PTCA, gender and age are factors predicting QOL after PTCA. The adaptation of PTCA for those patients should be prudently and inclusively taken into consideration to extend their QOL.

Adult↗

PubMed1997

[Histopathological examinations of dural arteriovenous malformations of posterior fossa].

Two cases of dural arteriovenous malformation (DAVM) of the posterior fossa were presented and a histopathological examination was described. After embolization of the feeding arteries, DAVMs of the posterior fossa were removed with the adjacent sinus. Serial sections of the surgical specimens showed an abnormal mass with dilated, tortuous vessels of varying diameters in the sinus wall, and partially hyalinized connective tissue around the vessels. The elastic lamina of the sinus wall was interrupted and a mass of abnormal vessels developed into the subintimal layer of the sinus. Fistulas, about 200 microns in diameter, were formed between arterialized dural veins and dural arteries which had obvious internal elastic lamina. An opening of the fistula of the abnormal vessel, 25 microns in diameter, to the sinus lumen was also seen. No stage of organized thrombus could be seen in the sinus lumen. These findings strongly suggested that physiologically existing arteriovenous fistulas within the dura mater, which have been reported by Kerber et al, had developed due to many factors which increase intracranial pressure. They protruded into the sinus lumen in such a way that it could cause stenosis or obstruction of the sinus. In conclusion it can be said that an obstructive lesion of dural sinus is considered of itself to be DAVM in most cases and sinus thrombosis is the result of the DAVM.

Adult↗

PubMed1997

[Molecular genetics and merosin abnormality in Fukuyama-type congenital muscular dystrophy (FCMD)].

Fukuyama-type congenital muscular dystrophy (FCMD), the second most common form of muscular dystrophy in Japan, is an autosomal recessive severe muscular dystrophy associated with brain anomalies. After our initial mapping of FCMD to chromosome 9q31-33, we revealed that the gene lies within a region of < 100 kb containing D9S2107(9q31) by linkage-disequilibrium mapping. A-3 kb insertion was found in most FCMD chromosomes with the founder haplotype. On the other hand, a significant reduction in immunostaining of an extracellular matrix, laminin alpha 2 (merosin) has been noted in the FCMD muscle. Others reported basal lamina abnormalities in the FCMD muscle and brain in electron microscopic examination. We here describe recent advances in molecular genetics of FCMD and abnormalities of the basement membranes.

Basement Membrane↗