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Biomedical subjects

T Tsuzuki

Publications and source records attributed to T Tsuzuki.

At least 109 records · Page 6Linked to original sources

Interleukin 8 and biocompatibility of dialysis membranes.

To determine whether interleukin 8 (IL-8) can be used as an index of biocompatibility of dialysis membranes, the effects of hemodialysis (HD) on plasma IL-8 levels and the expression of IL-8 mRNA in peripheral blood mononuclear cell (PBMC) were compared among regenerated cellulose (RC), polyacrylonitrile (PAN) and polymethylmethacrylate (PMMA) dialyzers. HD using RC dialysers significantly increased plasma IL-8 levels and induced abundant expression of IL-8 mRNA in PBMC. HD using PMMA dialyzers also increased plasma IL-8 levels and induced slight expression of IL-8 mRNA. In contrast, HD using PAN dialyzers neither increased plasma IL-8 levels nor induced the expression of IL-8 mRNA. In vitro studies demonstrated that IL-8 was considerably adsorbed by PAN membranes and not at all by RC and PMMA. These studies indicate that plasma IL-8 level and expression of PBMC IL-8 mRNA can be used as indices of biocompatibility of dialysis membranes.

Acrylic Resins↗

Immunohistochemical study of glutathione S-transferase-pi in meningiomas.

Immunostaining for glutathione S-transferase-pi was investigated in various subtypes of meningioma for the purpose of biological characterization. Specimens included five normal meninges and 25 meningiomas (10 meningothelial type, 6 fibrous type, 5 transitional type, 3 microcystic type, and 1 secretory type). In the meningothelial type, most cells showed strongly positive staining. In the fibrous type, all cells were negative. In the transitional type, only the meningothelial components were positive. In the microcystic type, meningothelial cell clusters and arachnoid trabecular cells were positive. In the secretory type, the meningothelial components and the pseudopsammoma-body-producing cells were positive. These results suggest that the meningothelial type and the fibrous type have a different basis of development and biological features. The results also suggest that arachnoid trabecular cells and meningothelial cells share the same origin, and that the arachnoid trabecular cells serve as supportive cells and as cells which detoxify harmful substances in the subarachnoid space. The pseudopsammoma-body-producing cells in the secretory type represent the outcome of epithelial differentiation of meningothelial cells with their biological character being preserved.

Culture Techniques↗

Intratumor cellular heterogeneity and alterations in ras oncogene and p53 tumor suppressor gene in human prostate carcinoma.

To assess the potential role of ras oncogene activation and p53 tumor suppressor gene mutations in the development of human prostate carcinoma, nine cases of histologically heterogeneous prostate tumors obtained from total prostatectomies were probed for these specific events. Each tumor was divided into 5 to 10 areas according to different growth or histological patterns. Targeted DNA sequences coding for ras and p53 were amplified by the polymerase chain reaction, analyzed by single-strand conformational polymorphisms, and confirmed by direct DNA sequencing. Point mutations of the ras gene were found in three of the nine tumors. Two contained K-ras codon 13 and H-ras codon 61 mutations, found in only one and three areas of each lesion, respectively. The third tumor contained two different point mutations in K-ras codons 13 and 61 in different foci of the sample. Loss of heterozygosity at the polymorphic codon 72 in the p53 gene was detected in two of four informative cases (50%) showing fragment cleavage by restriction fragment length polymorphism analysis. Mutations in p53, missense transversions, single base insertions, and two base deletions were also detected in three tumors. The present results reveal mutated ras and p53 occasionally occurring in small foci of the tumor and that genetic mutations in p53, as opposed to those in ras, are more closely associated with invasive growth of heterogeneous prostate carcinoma.

Carcinoma↗

[Recent studies on mammalian DNA repair mechanisms].

Errors in the replication of DNA are a major source of spontaneous mutation and a number of cellular functions correct these errors to maintain a low frequency of spontaneous mutation. First, we focused on two enzymes, 8-oxo-dGTPase and O6-methylguanine-DNA methyltransferase, which may be involved in the processes of spontaneous and induced mutagenesis, respectively. These enzymes are present in various organisms, from bacteria to mammalian cells, and appears to be responsible for preventing the occurrence of such mutations at the pre-replicational step. In addition to these two, the other mechanisms, such as nucleotide excision repair and mismatch repair, that also keep mutation rate low we reviewed. Genetic defects in one of the genes involved in DNA repair mechanisms have been linked to the high incidence of cancer, such as Xeroderma pigmentosum and hereditary nonpolyposis colorectal cancer.

Animals↗

Clinicopathological study on pineocytoma.

Six cases of pineocytoma, which had developed in the parenchyma of the adult pineal body, were examined immunohistochemically and under an electron microscope, after the malignancy of each case had been determined using our classification. One case was rated as grade 1 showing a lobular structure and resembling the normal pineal body. Two cases were rated as grade 2 without a lobular structure but with pineocytomatous rosettes (P-rosettes). Two cases were rated as grade 3 without P-rosettes but with few mitotic figures. One case was rated as grade 4 with marked cellular pleomorphism, numerous mitotic figures and necrotic foci. When examined immunohistochemically, neuron-specific enolase was positive but glial fibrillary acidic protein was negative in all cases. Under an electron microscope, all cases showed abortive synapses, and clear or dense core vesicles. These findings allow us to make two conclusions. First, pineocytoma is always a tumor of neuronal lineage, regardless of their grade of malignancy. Second, the grade 4 pineocytoma should be distinguished from the type of tumor classically called "pineoblastoma." That is, the former seems to be a biologically dedifferentiated tumor, while the latter seems to be biologically undifferentiated tumor.

Adult↗

Combined resection of the pancreas and portal vein for pancreatic cancer.

Between March 1976 and December 1992, 137 (57 per cent) of 239 patients with pancreatic duct cell cancer underwent resection; 79 (58 per cent) of the 137 had combined resection of the pancreas and portal vein. Sixty-three of the 79 patients underwent resection of the portal vein alone; six died (mortality rate 10 per cent). The mortality rate was the same as that in 58 patients with no resection of the portal vein. In the remaining 16 patients adjacent arteries were also resected, with seven deaths. Of patients with resection of the portal vein alone who underwent curative resection, four survived more than 5 years, accounting for nearly half of the nine 5-year survivors. Combined resection of the pancreas and portal vein is associated with both an increased resectability rate and improved long-term survival.

Adult↗

Kinetics of intestinal intraepithelial lymphocytes during acute graft-versus-host disease in mice.

We examined the kinetics of intestinal intraepithelial lymphocytes (IEL) and the incidence of apoptosis at villus or crypt sites during the development of non-irradiated acute graft-versus-host disease (GVHD). The first IEL to increase were host-origin on day 3 and the donor-derived IEL appeared first on day 12 after GVHD induction. Unique CD3+CD4+CD8 alpha/alpha+ IEL were significantly increased on day 6 and an appreciable number of IEL bearing T cell receptor V beta capable of recognizing self-superantigen were detected on day 9. The sudden appearance of apoptosis and reduction of mitotic activity occurred on day 12, accompanied by a dramatic decrease of CD3+CD4-CD8 alpha/alpha+ IEL of host origin. CD8 alpha/alpha+ IEL of host origin, which expand and then decrease by apoptosis at the early stage of acute GVHD, may be associated with pathogenesis of the enteropathy occurring during acute GVHD.

Animals↗

Genomic structure and chromosome location of the human mutT homologue gene MTH1 encoding 8-oxo-dGTPase for prevention of A:T to C:G transversion.

8-Oxo-dGTP (8-oxo-7,8-dihydrodeoxyguanosine triphosphate) is produced by active oxygen species in the nucleotide pool of the cell and can be incorporated into cellular DNA. Human cells contain enzyme activity that hydrolyzes 8-oxo-dGTP to 8-oxo-dGMP, thereby preventing occurrence of mutations, caused by misincorporation. When the cDNA for human 8-oxo-dGTPase was expressed in Escherichia coli mutT- mutant cells devoid of self 8-oxo-dGTPase activity, the elevated level of spontaneous A:T to C:G mutation frequency reverted to normal. We isolated the genomic sequence encoding the enzyme and named the gene MTH1 (for mutT human homologue). This gene is composed of at least 4 exons, spans approximately 9 kb, and is located on human chromosome 7p22.

Amino Acid Sequence↗

Lack of low Km diazepam N-demethylase in livers of poor metabolizers for S-mephenytoin 4'-hydroxylation.

Metabolism of diazepam was studied in vitro to identify the forms of cytochrome P450 (CYP) responsible for N-demethylation (nordazepam formation) and 3-hydroxylation (temazepam formation), using liver microsomes obtained from extensive (EM) and poor metabolizers (PM) for S-mephenytoin 4'-hydroxylation. Involvement of at least two P450 forms in diazepam N-demethylation was suggested by a biphasic pattern in Lineweaver-Burk and Eadie-Hofstee plots from the EM, whereas a monophasic pattern was observed from the PM liver microsomes. The kinetic parameters for the N-demethylation in the EM group were: Km 1, 19.4 +/- 0.4 microM; Vmax 1, 0.27 +/- 0.04 nmol min-1 per mg protein; Km 2, 346 +/- 34 microM; Vmax2, 1.82 +/- 0.63 nmol min-1 per mg protein (n = 3, mean +/- SD). The PM group showed the mean values of Km and Vmax (Km, 319 +/- 30 microM; Vmax, 1.49 +/- 0.62 nmol min-1 per mg protein) (n = 3) similar to those of Km2 and Vmax2 in the EM group. An antibody raised against CYP2C9 (anti-human CYP2C) strongly inhibited diazepam N-demethylation in EM liver microsomes at a low substrate concentration (20 microM). However, the anti-human CYP2C showed no clear inhibition of N-demethylation in EM liver microsomes at a high substrate concentration (200 microM). Diazepam N-demethylation in PM liver microsomes was not clearly inhibited by the anti-human CYP2C at either the low or high substrate concentrations. These data suggest that different P450 forms mediated diazepam N-demethylation in EM and PM liver microsomes, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies↗

Progressive activity in latent prostate carcinoma defined by argyrophilic staining of the nucleolar organizer regions (AgNOR).

Argyrophilic staining of the nucleolar organizer regions (AgNOR) was studied in 30 cases of benign prostatic hyperplasias (BPH), 17 cases of latent prostate carcinomas, 50 cases of clinical carcinomas and seven cases of metastatic lesions from prostate carcinomas. The criteria for these comparisons were the number of positive-staining dots per nucleus, the area of the dots, and a relative score determined by multiplying the number of positive-staining dots in the nuclei by the areas of the dots. Overall, there were no significant differences in these three parameters between BPH and latent carcinomas. Among latent carcinomas, however, significantly higher AgNOR scores were observed for infiltrative lesions than for non-infiltrative lesions. AgNOR dot number, area and score increased as tumors became less differentiated, with no significant differences detected in metastatic versus non-metastatic carcinomas. These results suggest that some latent tumors are similar in biological behavior, such as cell proliferation, to clinical carcinoma.

Carcinoma↗

Medulloblastoma associated with cysts and calcifications--case report.

An 11-year-old boy presented with medulloblastoma occurring in the cerebellar vermis. Computed tomography and magnetic resonance imaging revealed numerous cysts and calcifications in the tumor. The tumor was subtotally removed and cellular synchronization radiation therapy given. He was discharged without neurological deficits. Histological examination showed the cysts represented necrotic foci. Macrophages, which appeared around the necrotic foci, were important in the development of the calcifications via proliferation of collagen fibers.

Brain↗

Pleomorphic adenoma of the lacrimal gland manifesting as exophthalmos in adolescence--case report.

A 16-year-old girl presented with a pleomorphic adenoma of the lacrimal gland manifesting as left painless exophthalmos which had persisted for 3 years. Computed tomography revealed a tumor about 15 mm in diameter in the superolateral site of the left orbit. The tumor was removed completely by combined orbitofrontal craniotomy through a transcranial approach. Histological examination demonstrated the growth of tumor cells as glandular cavities or sheets, with myxoid and partly chondroid connective tissue stroma. Pleomorphic adenoma of the lacrimal gland is unusual in adolescents.

Adenoma, Pleomorphic↗

[A case of anti-phospholipid antibody syndrome associated with typical mesangiolysis].

An 18-years-old female was admitted to our hospital because of severe edema, that had developed within one week, and massive proteinuria. She has been given treatment for mild proteinuria and Raynaud's phenomenon. Before the edema developed, she complained of recurrent attack of migraine associated with scintillating scotoma. At admission, she was suffering from butterfly erythema, hydropericardium and ascites. The results of tests for antinuclear antibodies and ENA antibodies were negative, but those for BFP and IgG-anticardiolipin antibody were positive, and the platelet and complement levels were low. Renal biopsy revealed typical mesangiolysis without any sign of hyperplastic nephritis. Electron microscopy demonstrated the deposition of microfibrillar structures in the mesangial areas. She was diagnosed as having SLE-antiphospholipid antibody syndrome. After the administration of prednisolone 40mg/day, the edema, Raynaud's sign and proteinuria disappeared. Migraine was improved by the additional use of warfarin, and the platelet count was normalized. These findings suggest that in this case, acute nephrotic symptom developed due to hemangioendothelial injury caused by anti-phospholipid antibody.

Adolescent↗

Extensive resection of the bile ducts combined with liver resection for cancer of the main hepatic duct junction: a cooperative study of the Keio Bile Duct Cancer Study Group.

BACKGROUND: It is necessary to elucidate whether extensive resection of the bile ducts combined with liver resection is a feasible and valid procedure for cancer of the main hepatic duct junction. METHODS: Based on a multi-institutional study, resectability rate, operative mortality, long-term survival, and factors contributory to long-term survival were investigated. RESULTS: Between January 1973 and December 1991, a total of 158 patients with this cancer were admitted to Keio University Hospital and six affiliated institutions. Eighty-three (53%) of the 158 patients underwent resection, with seven (8.4%) postoperative deaths. The operations were performed by seven surgeons who were in charge of liver surgery at each respective institution. The 5-year actuarial survival rate of the 83 patients who underwent resection was 20%. Twelve patients survived more than 5 years, and these patients underwent curative resection. Three of the 12 patients were doing well after 10 years. Procedures of liver resection were right trisegmentectomy in two patients and left lobectomy with resection of the right portal vein in one. CONCLUSIONS: It is clear that cancer of the main hepatic duct junction has become a curable disease. The operation is a valid procedure that can be widely practiced by competent surgeons.

Adenocarcinoma↗

Cloning and expression of cDNA for a human enzyme that hydrolyzes 8-oxo-dGTP, a mutagenic substrate for DNA synthesis.

8-Oxoguanine (8-oxo-7, 8-dihydroguanine) is produced in DNA, as well as in nucleotide pools of cells, by active oxygen species normally formed during cellular metabolic processes. 8-Oxoguanine nucleotide can pair with cytosine and adenine nucleotides at almost equal efficiencies, and transversion mutation ensues. Human cells contain enzyme activity, which hydrolyzes 8-oxo-dGTP to 8-oxo-dGMP, and this enzyme is responsible for preventing misincorporation of 8-oxoguanine into DNA. We purified this particular human enzyme to physical homogeneity and determined a partial amino acid sequence. We then cloned the cDNA for human 8-oxo-dGTPase and examined its nucleotide sequence. The human protein comprises 156 amino acid residues and has some sequence homology with the Escherichia coli MutT protein, which has a distinct 8-oxo-dGTPase activity. When the human cDNA was expressed in E. coli mutT- mutant cells, there was a significant amount of 8-oxo-dGTPase activity. In such cells, the frequency of spontaneous mutation was greatly reduced. We propose that the human 8-oxo-dGTPase protects genetic information from the untoward effects of endogenous oxygen radicals.

Amino Acid Sequence↗

Expression of nm23-H1 and nm23-H2 proteins in prostate carcinoma.

The nm23 gene products/nucleoside diphosphate (NDP) kinase expression in prostate carcinomas and benign hyperplasias was evaluated immunohistochemically. Monoclonal antibodies against nm23-H1 and nm23-H2 proteins were prepared using the corresponding proteins fused with glutathione S-transferase as immunogens. Of the 80 cases of nonmetastatic prostate carcinoma examined, 74% (59/80) and 60% (48/80) were immunoreactive for nm23-H1 or nm23-H2 protein, respectively. Negative staining for nm23-H1 occurred in 83% of metastatic lesions, while 34% were negative for nm23-H2. All primary tumors corresponding to the metastases examined showed positive immunostaining for nm23-H1, indicating an inverse relationship between expression of this protein and metastatic status. nm23-H2 protein was detected in 83% of primary tumors and its expression appeared to be significantly correlated to the degree of histological differentiation. In contrast, all cases of benign prostatic hyperplasia showed elevated levels of both nm23-H1 and nm23-H2 expression. These data suggest that the nm23/NDP kinase may play a role in suppressing the expression of malignant potential in prostate carcinomas.

Adenocarcinoma↗

Effect of hemodialysis on plasma levels of vasoactive peptides: endothelin, calcitonin gene-related peptide and human atrial natriuretic peptide.

To determine the role of vasoactive peptides such as endothelin (ET), calcitonin gene-related peptide (CGRP) and human atrial natriuretic peptide (hANP) in the regulation of blood pressure in uremic patients, and to determine the effect of various types of dialyzer membranes on hemodialysis (HD)-induced changes in plasma levels of such peptides, plasma ET, CGRP and hANP were measured in HD patients and patients on continuous ambulatory peritoneal dialysis (CAPD). Plasma levels of ET, CGRP, and hANP were significantly higher in HD and CAPD patients than in healthy subjects. There were no significant differences in plasma levels of ET, CGRP, and hANP between hypertensive and normotensive HD patients, and no significant correlation was observed between HD-induced changes in plasma levels and changes in blood pressure. Plasma levels of ET decreased when HD was performed using high-flux membranes, such as polyacrylonitrile (PAN), polymethyl methacrylate (PMMA) and cellulose triacetate (CTA), but did not decrease using a saponified cellulose (SC) membrane. Plasma levels of CGRP decreased in the case of PAN, but increased significantly with PMMA and showed no change with SC and CTA. Plasma levels of hANP decreased in all types of dialyzer membranes due to decreased secretion. These results indicate that the effect of HD on plasma levels of ET and CGRP, but not hANP, depends on the type of dialyzer membrane used.

Atrial Natriuretic Factor↗