Biomedical subjects

H Hashimoto

Publications and source records attributed to H Hashimoto.

At least 127 records · Page 7Linked to original sources

PubMed1993

Effects of preoperative transcatheter hepatic arterial chemoembolization for hepatocellular carcinoma. The relationship between postoperative course and tumor necrosis.

BACKGROUND: The effects of preoperative transcatheter arterial chemoembolization (TAE) for hepatocellular carcinoma (HCC) remain a matter of controversy. METHODS: Seventy-two patients with HCC were entered in the study; the patients did not have the risk factors for disease recurrence of tumor larger than 5 cm in diameter, the presence of venous invasion, or intrahepatic metastasis. Only patients with 3 years of follow-up after curative resection were selected. Forty-six underwent TAE (Group I) and 26 did not undergo TAE (Group II). Group I was divided into three subgroups according to the degree of tumor necrosis: IA, complete necrosis; IB, partial necrosis; and IC, no necrosis. Group II was divided into two subgroups: IIB, partial necrosis; and IIC, no necrosis. RESULTS: Preoperative TAE did not improve the average disease-free survival rates of the group as a whole. For patients undergoing TAE, the survival rate of Group IB was significantly worse than that of Groups IA or IC. The survival rate of Group IB was worse than that of Group II, but the difference was not significant. In Group II, the survival of Group IIB was worse than that of Group IIC. Histologically, residual tumor cells lacking mutual contact were detected in some patients in Group IB. CONCLUSION: These results indicate that partial tumor necrosis caused by preoperative TAE or spontaneous tumor necrosis per se might facilitate postoperative disease recurrence. This may occur because in patients with partial necrosis, the remaining tumor cells are less firmly attached and more likely to be dislodged into the bloodstream during hepatic resection.

Adult↗

PubMed1993

Gene structure of CYP3A4, an adult-specific form of cytochrome P450 in human livers, and its transcriptional control.

CYP3 A4 is the adult-specific form of cytochrome P450 in human livers [Komori, M., Nishio, K., Kitada, M., Shiramatsu, K., Muroya, K., Soma, M., Nagashima, K. & Kamataki, T. (1990) Biochemistry 29, 4430-4433]. The sequences of three genomic clones for CYP3A4 were analyzed for all exons, exon-intron junctions and the 5'-flanking region from the major transcription site to nucleotide position -1105, and compared with those of the CYP3A7 gene, a fetal-specific form of cytochrome P450 in humans. The results showed that the identity of 5'-flanking sequences between CYP3A4 and CYP3A7 genes was 91%, and that each 5'-flanking region had characteristic sequences termed as NFSE (P450NF-specific element) and HFLaSE (P450HFLa specific element), respectively. A basic transcription element (BTE) also lay in the 5'-flanking region of the CYP3A4 gene as seen in many CYP genes [Yanagida, A., Sogawa, K., Yasumoto, K. & Fujii-Kuriyama, Y. (1990) Mol. Cell. Biol. 10, 1470-1475]. The BTE binding factor (BTEB) was present in both adult and fetal human livers. To examine the transcriptional activity of the CYP3A4 gene, DNA fragments in the 5'-flanking region of the gene were inserted in front of the simian virus 40 promoter and the chloramphenicol acetyltransferase structural gene, and the constructs were transfected in HepG2 cells. The analysis of the chloramphenicol acetyltransferase activity indicated that (a) specific element(s) which could bind with a factor(s) in livers was present in the 5'-flanking region of the CYP3A4 gene to show the transcriptional activity.

Adult↗

PubMed1993

Proliferating cell nuclear antigen in hepatocellular carcinoma and small cell liver dysplasia.

BACKGROUND: Recently, proliferating cell nuclear antigen (PCNA) has been measured by using a monoclonal antibody in a variety of malignant neoplasms. METHODS: The authors evaluated cell proliferative activity by immunostaining for PCNA in 92 hepatocellular carcinoma nodules and 14 lesions of small cell liver dysplasia. RESULTS: The average PCNA labeling indices (LI) in Grades I, II, III, and IV were 12.2%, 17.5%, 53.7%, and 83.9%, respectively. There were statistically significant differences in the PCNA LI between all the histologic grades, except for Grades I and II. The less differentiated the histologic grade, the higher the PCNA LI became. This finding was also recognized in a hepatocellular carcinoma showing a "nodule in a nodule" appearance, in which the less-differentiated inner nodule had a higher PCNA LI than did the well-differentiated outer lesion. For an analysis of the disease-free survival in 74 patients with clinical follow-up data, 2 groups of patients with a PCNA LI higher and lower than the average level (32.0%) were compared. The disease-free survival rate after surgery was significantly higher (P < 0.005), and the venous invasion was significantly less frequent (P = 0.0003) in the low PCNA LI group than in the high PCNA LI group. The average PCNA LI in small cell liver dysplasia was 13.9%, which was almost equal to that of Grades I and II hepatocellular carcinoma. CONCLUSIONS: The PCNA LI of hepatocellular carcinoma showed a close correlation with both the histologic findings and the biologic behavior. Small cell liver dysplasia was a small round focus having proliferative activity similar to that of Grades I and II hepatocellular carcinoma.

Aged↗

PubMed1993

The primary structure of two proteins from the small ribosomal subunit of rice.

We isolated two rice cDNAs which encode an open reading frame of 117 amino acids or 82 amino acids. Their deduced amino acid sequence correspond to the ribosomal proteins (r-protein). A comparison of the amino acid sequence shows that the deduced amino acid sequence of one cDNA is homologous to the rat r-protein S20 and Xenopus r-protein S22. Another encoded products with a high degree of homology to the rat r-protein S21 and the yeast r-protein YS25.

Amino Acid Sequence↗

PubMed1993

Transitional cell carcinoma pattern in primary carcinoma of the fallopian tube.

BACKGROUND: A broad papillary proliferation resembling that in transitional cell carcinoma (TCC) of the urinary bladder was seen in 12 of 21 primary carcinomas of the Fallopian tube (PCFT). METHODS: According to their predominant histologic pattern (more than 50%), PCFT were classified into 9 TCC-predominant and 12 non-TCC-predominant tumors. The two groups were compared by clinicopathologic, histochemical, and immunohistochemical means. RESULTS: TCC-predominant tumors were grossly solid and microscopically demonstrated more frequent tumor necrosis and spindled tumor cells than non-TCC-predominant tumors. Mucin histochemistry revealed a correlation between TCC-predominant tumor and sulfomucin-predominant secretion and between non-TCC-predominant tumor and sialomucin-predominant secretion. Immunohistochemical studies for cytokeratins, vimentin, epithelial membrane antigen (EMA), Leu-M1, carcinoembryonic antigen (CEA), and CA 125 were not useful for discrimination between the two groups. Both groups showed similar features in patient age, clinical stage, cytology of ascites or peritoneal washing, and serum CA 125 level. Despite the similarity in treatment (surgery and postoperative chemotherapy) between the two groups, TCC-predominant tumors tended to relapse later (mean, 31.2 months after diagnosis) than non-TCC-predominant tumors (mean, 14.4 months after diagnosis), resulting in a significant difference in the 2-year disease-free survival rate. CONCLUSIONS: TCC pattern and non-TCC pattern are considered to be worthy of distinction in PCFT.

Adult↗

PubMed1993

High-risk human papillomavirus infections and overexpression of p53 protein as prognostic indicators in transitional cell carcinoma of the urinary bladder.

Ninety Japanese patients with transitional cell carcinoma of the urinary bladder were investigated for tumor incorporation of DNA for high-risk human papillomavirus (HPV) types 16, 18, and 33 by in situ hybridization with biotinylated DNA probes. In addition, immunohistochemical analysis of p53 protein expression was performed with an antibody to p53 protein. Twenty-eight tumors were positive for HPV DNA, and multiple HPV infection was detected in 17 cases. Positive nuclear staining of cancer cells by the antibody to p53 protein was detected in 32 cases. DNA for HPV 16, 18, and/or 33 and the overexpression of p53 protein were simultaneously observed in 6 tumors by using a mirror section method. The overexpression of p53 protein was frequently detected in invasive and nonpapillary tumors (P < 0.05) and in high grade tumors (P < 0.05). In contrast, HPV infection was more common in noninvasive and papillary tumors (P < 0.01). The patients with tumors positive for HPV DNA and/or p53 antibody had a significantly worse survival rate (P < 0.05). These results suggest that HPV infection or overexpression of p53 protein may be related to tumor behavior and may indicate a relatively poor prognosis in patients with transitional cell carcinoma.

Aged↗

PubMed1993

X-ray absorption spectroscopic studies of a transient intermediate in the reaction of cyanide metmyoglobin with dithionite by using rapid freezing.

The reaction of cyanide metmyoglobin (Mb+CN-) with dithionite produces a transient intermediate, supposed to be cyanide-ligated ferrous myoglobin. The Fe K-edge X-ray absorption spectrum of the intermediate has been measured by using rapid freezing and compared with those of Mb+CN- and deoxymyoglobin (deoxyMb). The shapes of the XANES (X-ray Absorption Near Edge Structure) spectra of Mb+CN- and the intermediate are very similar, including the intensity ratios of the peak C1 to D. This indicates that CN- remains bound with a linear Fe-C-N configuration in the intermediate. The absorption edge of the intermediate is shifted to 1.2 eV lower energy than that of Mb+CN-, reflecting a valence change in the heme iron. The EXAFS (Extended X-ray Absorption Fine Structure) spectrum of the intermediate closely resembles that of Mb+CN- but significantly differs from that of deoxyMb. Analysis shows that the average iron-nearest neighbor atom distance is 1.99 +/- 0.01 A for both Mb+CN- and the intermediate and 2.05 +/- 0.01 A for deoxyMb. These results imply that the local structure around the heme iron of Mb+CN- does not change upon reduction until the cyanide ligand is released.

Animals↗

PubMed1993

Characterization of inhibitory activities and binding mode of synthetic 6'-modified methyl N-acetyl-beta-lactosaminide toward rat liver CMP-D-Neu5Ac: D-galactoside-(2-->6)-alpha-D-sialyltransferase.

6'-Deoxy (12), 6'-thio (13), and 6'-O-tetrahydropyranosyl (14) analogues of methyl N-acetyl-beta-lactosaminide (3), were synthesized from lactose. NOE experiments proved that they adopt the same conformation as that of 3. Inhibition studies using these synthetic analogues, including the disulfide dimer 15, toward (2-->6)-alpha-sialytransferase (EC 2.4.99.1) revealed that the 6'-deoxy analogue 12 had remarkable inhibitory activity as the first acceptor-analogue inhibitor for this enzyme. It is noteworthy that the disulfide 15 also behaves as an inhibitor. The results indicated that chemical modification at the 6'-position of 3 did not cause much decrease in the binding affinity to the sialytransferase. Further, a novel possibility that the acceptor and the acceptor-analogue inhibitor can bind simultaneously to the sialytransferase was proposed based on the inhibition studies with 12 and CMP.

Amino Sugars↗

PubMed1993

Different functional forms of G-protein beta gamma-subunits, beta gamma-I and beta gamma-II, in bovine brain.

Heterotrimeric GTP binding regulatory proteins (G proteins) are involved in the signal transduction process in cells. We have previously demonstrated that G protein (Gi/o) in bovine brain contains two subspecies of the beta gamma-subunit, beta gamma-I and beta gamma-II, with distinct gamma subunits, i.e., gamma-I and gamma-II, but identical beta-subunit. We found that gamma-I agreed with the gamma-subunit reported elsewhere, while gamma-II was a novel gamma-subunit. In the present study we separated the fractions containing G-protein isoforms, Go*, Gi1, Go and Gi2, with a Mono Q column and they were subjected to 15% polyacrylamide gel electrophoresis. All isoforms were shown to possess both gamma subunits, gamma-I and gamma-II. The molar ratio of the two gamma-subunit isoforms was one to one, based on the relative intensity of Coomassie blue-stained bands. Differences in biological activity between G proteins composed of beta gamma-I and beta gamma-II were investigated. The amount of GTP gamma S bound to the alpha-subunit was larger in alpha beta gamma-I than in alpha beta gamma-II. The pertussis toxin-catalyzed ADP-ribosylation on alpha-subunit was enhanced by either beta gamma-subunit subspecies, but the effect was larger with beta gamma-I than with beta gamma-II. From gel filtration with a Sephacryl S 300, it appeared that all alpha- and either beta gamma-subunit, i.e., beta gamma-I or beta gamma-II, formed a trimer complex. These findings suggest the possible existence of two different functional forms in each G-protein isoform depending on the beta gamma-subunit subspecies.

Animals↗

PubMed1993

Lipoprotein lipase mass and activity in severe hypertriglyceridemia.

To clarify the role of defective lipoprotein lipase (LPL) in hypertriglyceridemia, the LPL masses and LPL activities in post-heparin plasma (PHP) were studied in severe hypertriglyceridemias. The developed sandwich enzyme immunoassay for the LPL was sensitive from 0.5 to 20 ng/ml of LPL in human PHP. The plasma LPL mass increased by heparin injection (30 USP units/kg) and was found to positively correlate with LPL activity. The mean LPL activity from PHP of normal controls was 2,960 +/- 1,057 nmol/ml/h. The mean LPL masses from human pre- and 15-min post-heparin plasma from normal subjects were 25 +/- 5 ng/ml and 224 +/- 60 ng/ml, respectively. Thus the specific activity of LPL from PHP of normal controls was calculated to be 13.3 mumol FFA released/h/microgram LPL. Among hypertriglyceridemic patients with over 1,000 mg/dl of serum triglyceride, the incidence of patients with LPL masses less than -2 standard deviations (S.D.) of those of average normal control subjects was found to be 27%. Seventy percent of patients showed specific activities within + 2 S.D. of those of average control LPL, and 30% showed significantly low specific activities less than -2 S.D. despite the fact that LPL masses were not less than -2 S.D. of the average normal controls. These results suggest that the evaluation of LPL masses in PHP would be useful for finding functionally defective LPL in patients with hypertriglyceridemia, and that up to 30% severe hypertriglyceridemias may have functionally defective LPL.

Adult↗

PubMed1993

The prognostic value of immunohistochemical staining for proliferating cell nuclear antigen in synovial sarcoma.

BACKGROUND: The biologic behavior of synovial sarcoma remains a matter of controversy. Some investigators considered proliferative activity to be an important prognostic factor in this tumor. METHODS: Fifty-six patients with synovial sarcoma were immunohistochemically studied with PC10, a monoclonal antibody to proliferating cell nuclear antigen (PCNA). The percentage of nuclear areas with positive staining for PCNA (PCNA score), quantified by using an image analyzer, was compared with nuclear atypia, tumor necrosis, mitoses, and survival. Fifty-one patients were available for survival analysis. DNA flow cytometry was performed on 30 patients and compared with PCNA score and survival. The prognostic variables were analyzed with a multivariate technique using the Cox hazard model. RESULTS: Nuclear atypia (mild, 14; moderate, 23; severe, 14), mitosis (low, 34; high, 17), and tumor necrosis (< 50%, 37; > 50%, 14) were found to highly affect survival in the log-rank test (P < 0.01). Sixteen patients with a high (> or = 12.5) PCNA score had a worse survival (P < 0.01) than did the 35 patients with a low (< 12.5) PCNA score. In patients in whom DNA flow cytometry was performed, the S+G2M-phase fraction showed no correlation with the clinical outcome. However, there was a significant relationship between the extent of PCNA staining and S+G2M fraction (correlation coefficient [CC] = 0.54; P = 0.002), although the CC between PCNA staining and the mitotic count was only 0.38. However, the ploidy pattern was not related to PCNA scores or prognosis. In a multivariate analysis, a high PCNA score (P = 0.017) and severe nuclear atypia (P = 0.0003) were strong prognostic factors. CONCLUSIONS: The results suggest that a high PCNA score is one of the poor prognostic factors in synovial sarcoma.

Adolescent↗

PubMed1993

Beta 1 integrin-mediated interaction with extracellular matrix proteins regulates cytokine gene expression in synovial fluid cells of rheumatoid arthritis patients.

Inflammatory cytokines have been implicated in the pathogenesis of rheumatoid arthritis (RA), whereas the mechanisms for constitutive production of inflammatory cytokines in affected joints are largely unknown. Recently, integrin-mediated interaction with extracellular matrix (ECM) proteins has been demonstrated to play a role in regulating cytokine production in T cells and monocytes. In this study, we investigated the contribution of the beta 1 integrin-mediated interaction with ECM proteins to the persistent cytokine gene expression in RA synovial fluid mononuclear cells (SFMNC). We examined mRNA expression of 14 cytokines in the SFMNC of three RA patients, which were either fresh or cultured overnight in serum-free medium on ECM-coated plates, by polymerase chain reaction with a panel of oligonucleotide primers specific for each cytokine. The persistent expression of various cytokine mRNA found in fresh SFMNC was maintained after overnight culture in serum-free medium on ECM proteins, especially on laminin (LM), but not on serum albumin. This effect of LM was inhibited by an anti-integrin beta 1 chain (CD29) mAb, as well as by an anti-CD3 mAb, indicating an important role of the beta 1 integrin-mediated interaction with ECM proteins in regulating persistent cytokine gene expression in RA SFMNC, and a key role of T cells in regulating inflammatory monokine production.

Adult↗

PubMed1993

Identification of a novel gamma-subunit from bovine brain GTP binding regulatory proteins (Gi/o).

Heterogeneity of the gamma-subunit of G proteins has been demonstrated by cDNA cloning and by partial sequence analyses. We have isolated two intact beta gamma-subunit isoforms from bovine brain Gi/o mixture, in which only gamma subunits are distinct (Sohma, H., et al. (1992) Biochem. Biophys. Res. Commun. 184, 175-182). In this study, we isolated the gamma-subunit isoforms, gamma-I and gamma-II, and examined their amino acid sequences. Both gamma-I and gamma-II had blocked N-terminal amino acid residues, and the terminal amino acids of both were able to be truncated by an acylamino-acid-releasing enzyme. Gamma-I seemed to be identical with the gamma-subunit reported elsewhere, while the gamma-II appeared to be a novel protein. Antibodies to synthetic peptides based on the part of the amino acid sequences of gamma-I and gamma-II reacted specifically to gamma-I and gamma-II, respectively.

Amino Acid Sequence↗

PubMed1993

Inhibitory glutamate response on cyclic AMP formation in cultured astrocytes.

We examined the effects of glutamate receptor agonists on cyclic AMP (cAMP) formation in cultured astrocytes. L-Glutamate reduced the cAMP formation induced by either isoproterenol (IC50 7 microM) or forskolin without affecting the basal level. Glutamate agonists reduced the cAMP formation in astrocytes with the following rank order of potency: L-glutamate > trans-(+/-)-1-aminocyclopentane-1,3-dicarboxylic acid (t-ACPD) = quisqualate. Pretreatment of astrocytes with pertussis toxin resulted in a partial reduction of the glutamate response and a complete attenuation of the t-ACPD response. These results suggest that astrocytes have another type of metabotropic glutamate receptor which inhibits adenylate cyclase through pertussis toxin-sensitive G-proteins.

Adenylate Cyclase Toxin↗

PubMed1993

A possible role of two hydrophobic amino acids in antigen recognition by synovial T cells in rheumatoid arthritis.

Synovial T cells play a crucial role in the pathogenesis of rheumatoid arthritis (RA) synovitis. We have quantitatively analyzed the T cell receptor (TcR) variable (V) region gene repertoire of freshly isolated synovial fluid (SF) T cells, comparing it with that of peripheral blood (PB) T cells in RA. The TcR V gene repertoire of PB and SF T cells in RA and osteoarthritis was heterogeneous. In contrast, V alpha 11 in SF was expressed to a greater degree in three of five RA patients, and increased levels of V beta 6, 1-3 were found in the SF of four of six RA, compared with paired PB. Of note, V beta 6, 1-3 was universally used in four RA patients with a disease duration of less than 10 years, irrespective of their HLA-DR types. This was in contrast to two other RA patients, suffering for more than 20 years, who showed different V alpha and V beta usages. beta-chain sequence analysis in RA patients with a preference for V beta 6, 1-3 has shown that a few clones dominated in SF, whereas polyclonality was observed in PB. These findings suggest oligoclonal expansion of T cells in response to specific antigen(s) in the SF of these patients with RA of relatively short duration. Concomitant use of two hydrophobic amino acids, leucine and valine in the D beta region was noticeable among the predominant SF clones. These two amino acids might directly contact a peptide specific for the induction of synovitis in RA patients. TcR-directed therapy may, therefore, be useful for the treatment of early RA synovitis.

Aged↗

PubMed1993

Isolation and characterization of a rice cDNA which encodes a ubiquitin protein and a 52 amino acid extension protein.

We isolated a rice cDNA clone encoding the ubiquitin protein fused to a ribosomal protein. This clone encodes a single ubiquitin polypeptide and extension protein of 53 amino acids. This extension protein shows a high degree of homology with those of the yeast ubil or ubi2 gene, both of which encode the same protein. Northern blot analysis suggested that the expression pattern of this gene is more similar to other ribosomal protein genes not linked to ubiquitin protein than to the polyubiquitin gene.

Amino Acid Sequence↗

PubMed1993

Immunohistochemical studies on S-100 cells in the anterior pituitary gland of Sprague Dawley rats and spontaneous dwarf rats.

The S-100 cells in the pituitary glands of adult male Sprague Dawley rats (SDs) and spontaneous dwarf rats (SDRs) were immunohistochemically examined using anti-S-100 alpha and anti-S-100 beta monoclonal antibodies. The immunoreactive cells against S-100 protein were divided into three subtypes on the basis of their immunoreactivity against subunits of S-100 protein: S-100 alpha dominant type (the alpha-type cell), S-100 beta dominant type (the beta-type cell) and immunoreactive against both S-100 alpha and S-100 beta (the alpha beta-type cell). In the SD, alpha-type cells represented 26% of the total S-100 immunoreactive cells (S-100 cells) and were localized in the peripheral area of the ventral region of the pituitary gland. This type of cell was observed forming clusters, with more abundant cytoplasm than the beta-type cell. The proportion of beta-type cells was 53%. They were diffusely distributed throughout the gland, and their processes were thicker than those of the alpha-type cell. In the SDR, the proportion of alpha-type cells was 55%, and they were observed throughout the gland. In contrast, beta-type cells totalled 12% and were localized in small areas of the central and peripheral region of the gland. The proportion of alpha beta-type cells was 21% in the SD and 33% in the SDR and they were observed forming small clusters in both animal groups. The proportion of alpha-type cells compared with the total of S-100-immunoreactive cells was significantly higher (P < 0.05) in the SDR than in the SD, while the proportion of beta-type cells was markedly lower (P < 0.05).

Animals↗

PubMed1993

Case report 793. Periosteal osteosarcoma of the clavicle.

A case of periosteal osteosarcoma in an 18-year-old boy has been reported. This is the first reported case of periosteal osteosarcoma arising in the clavicle. The radiological features in this case were entirely similar to those in long bones such as the femur and tibia. In addition to the radiological features and pathologic findings, various clinical aspects and prognosis were also discussed.

Adolescent↗