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Biomedical subjects

A Ito

Publications and source records attributed to A Ito.

At least 505 records · Page 28Linked to original sources
PubMed1994

Expression of the c-met protooncogene in human hepatocellular carcinoma.

The c-met protooncogene is a growth factor receptor with tyrosine kinase activity. Recently the hepatocyte growth factor was identified as the ligand for this receptor. Because the hepatocyte growth factor is a most potent mitogen in hepatocytes, possible involvement of c-met expression in hepatocarcinogenesis is suspected. In this study, we examined c-met expression in 23 hepatocellular carcinoma cases by means of Northern-blot analysis and an immunohistochemical study. Northern-blot analysis revealed c-met mRNA expression in the tumors of 6 of 19 patients (31.6%); in the immunohistochemical study, c-met protein was detected in 16 of 23 patients (69.6%). With both methods, c-met was found to be overexpressed in hepatocellular carcinoma compared with the surrounding normal liver. Comprehensive analysis showed that c-met protein expression was correlated with poor-to-moderate differentiation of cancer cells (p < 0.05). Tumor proliferative activity of hepatocellular carcinoma was evaluated by means of Ki-67 labeling index. All cases with increased tumor proliferative activity showed c-met protein expression, although the elevation of proliferative activity in the c-met-positive group was not statistically significant. These data suggest that the overexpression of c-met plays an important role in the development of hepatocellular carcinoma.

Adult↗
PubMed1994

[An evaluation study on arbekacin for MRSA-infectious diseases including pneumonia, septicemia and others].

Availability of arbekacin (ABK) was analyzed in the chemotherapy of 24 MRSA-infected patients with symptoms of pneumonia (12), sepsis (6) and others (6). Most patients had background diseases such as malignant tumors or cerebrovascular disorders. 47% (7/15) of them were immunologically abnormal. 17 of them had been previously treated with cephems, imipenem, minocycline or fosfomycin. The ABK therapy was performed with doses ranging 50-400 mg a day, divided into 1-3 times (mostly 100 mg x 2), and for 5-24 days. (18 patients were treated between 5 and 14 days). 14 patients (58%) received combined therapy with other antibiotics (mostly with beta-lactams, 12). The clinical efficacy rate of the ABK therapy was 62% (good, 13; fair, 4; ineffective, 4; unknown, 3). The bacteriological efficacies were: eradicated, 7 (44%); decreased, 4; no change, 5; unknown, 8. Side effects were found in 3 patients (oliguria, 2; eruption due to drug, 1) and one case resulted in serious renal disorder. Abnormal laboratory data were found in 7 cases. Above results have indicated that ABK is a useful antibiotic in chemotherapy of MRSA-infections.

Adult↗
PubMed1994

Expression of genes encoding connective tissue proteins in androgen-dependent SC115 tumors after androgen removal.

BACKGROUND: Shionogi carcinoma 115 (SC115) is an androgen-dependent medullary carcinoma with a compact cell pattern. When SC115 tumors grow in androgen-depleted hosts, spindle-shaped and round cells with abundant cytoplasm develop. These cells originate from the SC115 cells (Kitamura et al., Cancer Res 1979;39:4717; Terada et al., Lab Invest 1987;57:186). EXPERIMENTAL DESIGN: We investigated whether these spindle-shaped and round cells expressed mRNAs of noncollagenous connective tissue proteins, which are expressed by normal spindle-shaped cells and normal chondrocytes in developing bones. The expression and localization of osteonectin (OSN), osteopontin (OSP), matrix Gla protein (MGP), and osteocalcin (OSC) were determined by Northern blotting and in situ hybridization. RESULTS: No mRNA signals of these proteins were detectable in SC115 medullary carcinoma cells growing in DS mice that had been castrated but received injections of testosterone propionate. However, when the injection of TP was stopped, spindle-shaped and round cells with abundant cytoplasm developed. The former expressed OSN and OSP signals, and the latter OSN, OSP, and MGP signals. CONCLUSIONS: Transcripts of OSN, OSP, and MGP were expressed by some SC115-derived cells during the differentiation events that occurred after androgen removal. These results provide molecular biologic evidence that a tumor of epithelial origin can progress along the connective tissue differentiation pathway.

Amino Acid Sequence↗
PubMed1994

Effects of glycosaminoglycan polysulfate on extracellular matrix metabolism in human skin cells.

The effects of chondroitin polysulfate (CPS), a semi-synthetic oversulfated chondroitin sulfate, on the metabolism of extracellular matrix in human skin cells were examined. CPS accelerated the production of glycosaminoglycans (GAGs) in human dermal fibroblasts in a dose dependent manner (0.1-3.0 micrograms/ml), but did not modulate the production of noncollagenous protein and collagen, or [3H]-thymidine incorporation into DNA. However, higher concentrations (> 10 micrograms/ml) of CPS suppressed the [3H]-thymidine uptake by fibroblasts. More than 80% of total synthesized GAGs were found to be hyaluronate, whereas CPS did not alter their composition. These results indicated that CPS preferentially enhances the production of GAGs in human dermal fibroblasts, and that GAGs and DNA synthesis in the fibroblasts are independently regulated. Furthermore, CPS might be a unique material able to maintain the level of GAGs in the human skin.

Cells, Cultured↗
PubMed1993

Involvement of protein kinase C in the interleukin 1 alpha-induced gene expression of matrix metalloproteinases and tissue inhibitor-1 of metalloproteinases (TIMP-1) in human uterine cervical fibroblasts.

The role of protein kinase C in the interleukin 1 (IL-1)-mediated production of pro-matrix metalloproteinases (proMMPs) and tissue inhibitor-1 of metalloproteinases (TIMP-1) in human uterine cervical fibro-blasts has been investigated. IL-1 and a protein kinase C activator, 12-O-tetradecanoylphorbol 13-acetate (TPA) augmented the production of proMMP-1 (interstitial procollagenase), proMMP-3 (prostromelysin-1) and TIMP-1, but their effects were inhibited by the protein kinase C inhibitors 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7) and staurosporine in a dose-dependent manner. The suppressive effect of H-7 and staurosporine on the IL-1-induced production of proMMPs-1 and -3 and TIMP-1 resulted from the decrease in the steady-state levels of their mRNAs. When protein kinase C was down-regulated by treating the cells with a high level of TPA, the inductive effect of IL-1 upon proMMP-3 production was reduced considerably. These results indicate that protein kinase C mediates the IL-1-induced production of proMMPs-1 and -3 and TIMP-1 at the pretranslational level in human uterine cervical fibroblasts. On the other hand, neither IL-1 nor TPA modulated the production of proMMP-2 (progelatinase A). Both IL-1 and TPA also accelerated the production of prostaglandin E2 (PGE2) by cervical fibroblasts. However, the treatment of the cells with staurosporine in the presence of IL-1 or TPA further augmented PGE2 synthesis, suggesting that the increased synthesis of PGE2 by IL-1 treatment is mediated via signalling pathways distinct from those of proMMPs-1 and -3 and TIMP-1.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1993

Antiproliferative effects of isoflavones on human cancer cell lines established from the gastrointestinal tract.

Seven isoflavones, biochanin A, daidzein, genistein, genistin, prunectin, puerarin, and pseudobaptigenin were tested for cytostatic and cytotoxic effects on 10 newly established cancer cell lines of the human gastrointestinal origin. Proliferation of HSC-41E6, HSC-45M2, and SH101-P4 stomach cancer cell lines was strongly inhibited by biochanin A and genistein, whereas other stomach, esophageal, and colon cancer lines were moderately suppressed by both compounds. Biochanin A and genistein were cytostatic at low concentrations (< 20 micrograms/ml for biochanin A, < 10 micrograms/ml for genistein) and were cytotoxic at higher concentrations (> 40 micrograms/ml for biochanin A, > 20 micrograms/ml for genistein). DNA fragmentation was observed at cytotoxic doses of both compounds, indicating the apoptotic mode of cell death by the compounds. Chromatin condensation and nuclear fragmentation of each cell line were also observed. The advent of apoptosis was dose dependent for both isoflavones. Biochanin A suppressed tumor growth of HSC-45M2 and HSC-41E6 lines in athymic nude mice. Our results suggest that two of isoflavone derivatives, biochanin A and genistein, inhibit the cell growth of stomach cancer cell lines in vitro through activation of a signal transduction pathway for apoptosis. Moreover, in vivo experiments demonstrate that biochanin A can be used as an anticancer agent.

Animals↗
PubMed1993

Regulation of hyaluronate production by interleukin 1 in cultured human chorionic cells.

Human chorionic cells in culture synthesized and secreted a large amount of hyaluronate as well as tissue collagenase. When these cells were treated with human recombinant interleukin 1 alpha (hrIL-1), the biosynthesis and secretion of hyaluronate were predominantly accelerated, but those of sulfated glycosaminoglycans were not modulated. This promotive effect of hrIL-1 was not due to the increase in endogenous prostaglandins including prostaglandin E2 since cyclooxygenase inhibitors, indomethacin and diclofenac did not modulate the IL-1-mediated production of hyaluronate. On the other hand, the cotreatment of chorionic cells with hrIL-1 and cycloheximide suppressed the IL-1-mediated hyaluronate production, suggesting that protein, de novo, synthesis required for the enhancement of hyaluronate synthesis. Upon treatment with hrIL-1, the membrane bound-hyaluronate synthase activity was increased up to 5-fold in a time-dependent manner. On the other hand, when chorionic cells were treated with hrIL-1 and/or protein kinase C inhibitor, 1-(5-isoquinolinesulfonyl)-2-methyl-pyperadine hydrochloride (H7), the IL-1-mediated production of hyaluronate was effectively suppressed. Similarly, H7 effectively suppressed the protein kinase activator, 12-O-tetradecanoyl-phorbol-13-acetate-enhanced production of glycosaminoglycans with a similar extent. These results indicate that IL-1-induced acceleration of hyaluronate production was reflected on the increase in hyaluronate synthase activity, and that protein kinase C participates positively in the IL-1-signal transduction for the increased synthesis of hyaluronate in human chorionic cells.

Cells, Cultured↗
PubMed1993

[Noninvasive quantitative measurement of cerebral blood flow with 123I-IMP--lung monitoring method].

In order to perform a less invasive determination of regional cerebral blood flow (rCBF) using I-123-IMP, we used the lung clearance curve as a substitute for the arterial blood activity curve as an input function. We assumed that a major portion of the intravenously injected I-123-IMP initially accumulates in the lung and then is gradually cleared from the lung pool to enter the systemic circulation. In this case lung clearance could be considered nearly equal to the integral of arterial blood activity shown during the examination. We used a single probe detector to obtain the lung clearance curve as the difference between sequential lung activity and peak lung activity. The absolute value of the sequential change in arterial blood activity was estimated from the differentiated lung clearance curve compared with the arterial blood activity that was estimated by actual blood sampling once during the examination. The rCBF was calculated by the thus estimated arterial blood activity curve and brain activity by SPECT image using the microsphere model. The values of rCBF obtained by this method were similar to those obtained by the continuous arterial sampling method, and this lung monitoring method was thought to be applicable to clinical use.

Adult↗
PubMed1993

Molecular cloning of the smaller subunit(P52) of rat liver mitochondrial processing protease.

A cDNA encoding the smaller subunit (P52) of mitochondrial processing protease was isolated from a rat liver cDNA library, using cDNA fragment for yeast MAS1 as the probe. The deduced amino acid sequence is highly homologous to those of PEP from Neurospora crassa and MAS1 from Saccharomyces cerevisiae. After in vitro transcription and translation, the precursor peptide was imported into isolated rat liver mitochondria and processed to its mature form.

Amino Acid Sequence↗
PubMed1993

Developmental expression of flt3 mRNA in the mouse brain.

The expression and localization of flt3 mRNA were investigated using Northern blotting and in situ hybridization during the developmental process of the mouse brain. By Northern blotting, the expression of the flt3 gene was not detected in embryonic, neonatal, or early postnatal brains, but was markedly increased with age. In adult mice, flt3 was abundantly expressed in the cerebellum, moderately in the pons, and faintly in the thalamus and the cerebral cortex. By in situ hybridization, some neurons that expressed flt3 formed synaptic connections with each other. The present findings suggest that the flt3 gene expression is related to the cell type and the developmental process.

Age Factors↗
PubMed1993

PKC gamma gene expression is delayed in postnatal central nervous system of mi/mi mice.

In the central nervous system (CNS), the expression of protein kinase C (PKC) genes is strictly controlled by the developmental stage. We have examined the expression of PKC genes (cPKC alpha, beta, gamma, and nPKC delta, epsilon) in the process of the postnatal development in normal (+/+) C57BL/6 and microphthalmic (mi/mi) C57BL/6 mouse brains by Northern blotting and in situ hybridization. By Northern blotting, the expression level of cPKC gamma mRNA in mi/mi mice was significantly lower than that in +/+ littermates at d 9, 13, and 17. By in situ hybridization analysis, cPKC gamma mRNA-positive cells were detected in hippocampal and Purkinje cells in +/+ and mi/mi mice, but the magnitude of the signals in mi/mi mice was lower than that of +/+ mice, and the number of positive cells was smaller, whereas other isozymes (cPKC alpha, beta, and nPKC delta, epsilon) showed no significant difference between normal and mi/mi mice. The neuronal morphometric analysis by anti-P400 antibody revealed the same number and expression level of P400 protein in cerebellar Purkinje cells compared with +/+ mice. These results indicate that the deficiency of mi gene product causes the delayed expression of the cPKC gamma gene.

Animals↗
PubMed1993

In-vitro evaluation of the cytocompatibility of wear particles generated by UHMWPE/zirconia friction.

Cytotoxicity of wear products generated by UHMWPE/yttria partially stabilized zirconia (YPSZ) friction and UHMWPE/surface-nitrided Ti-6Al-4V friction in pseudo-extracellular fluid (PECF) at 37 degrees C was evaluated. Though the amount of abraded UHMWPE against YPSZ was almost the same as that against nitrided Ti-6Al-4V, the wear products generated by UHMWPE/YPZ friction significantly inhibited cell growth while those by UHMWPE/nitrided Ti-6Al-4V friction showed no growth inhibition. Dissolved Zr and Y ions were at least 70 times less than the amount causing growth inhibition. The cytotoxicity was caused mainly by the particles less than 0.22 mum in size. Amorphous zirconium-containing particles (5-20 nm) found in the PECF, formed presumably by stress corrosion, would be a responsible factor for the cytotoxicity.

Biocompatible Materials↗
PubMed1993

Vaccination with hatched but non-activated, non-viable oncospheres of Taenia taeniaeformis in rats.

The usefulness of hatched but non-activated oncospheres as a candidate vaccine was evaluated using a Taenia taeniaeformis/rat system, since preparation of these oncospheres in vitro is known to be very simple. The findings were: (1) rats vaccinated with non-viable oncospheres became completely resistant to challenge infection; (2) intra-venous injection was the most effective to induce complete resistance; (3) a single oncosphere was sufficient to induce complete resistance in infected rats, whereas approximately 50 and 500 non-viable oncospheres were required to evoke strong and complete resistance, respectively, in vaccinated rats. The usefulness of non-viable oncospheres without adjuvant is discussed.

Animals↗
PubMed1993

Separation of large and small granules from horseshoe crab (Tachypleus tridentatus) hemocytes and characterization of their components.

We designed a method for separating two types of granules, a smaller (S) but dense and a larger (L) but less dense granule from hemocytes of the horseshoe crab (Tachypleus tridentatus), using continuous sucrose density gradient centrifugation. The isolated L-granules contained at least three clotting factors plus a clottable protein, coagulogen, as the major component. The known anti-lipopolysaccharide factor and 7 additional unknown protein components were also present in the L-granules. Two known natural substrates, Pro-rich protein and 8.6 kDa protein, for limulus transglutaminase [Tokunaga, F., Yamada, M., Miyata, T., Ding, Y.-L., Hiranaga-Kawabata, M., Muta, T., Iwanaga, S., Ichinose, A., & Davie, E.W. (1993) J. Biol. Chem. 268, 252-261] were present in the L-granules. On the other hand, the isolated S-granules contained antimicrobial tachyplesins I and II (17 amino acids in length) as the major component, in addition to 6 unidentified proteins with molecular masses of less than 30 kDa. The structural analyses of tachyplesin analogs indicated that all these peptides of mature form are stored in the S-granules, together with a processing intermediate containing the COOH-terminal Gly-Lys sequence. We also found an Arg-rich protein of 22 kDa and a Leu-rich protein of 30 kDa in S-granules. Based on these observations, we speculate that protein components in L-granules, which probably contain all the factors essential for the limulus clotting system, participate in immobilization of invading microbes and that factors in the S-granules containing tachyplesins contribute to a self-defense system against invaders.

Amino Acid Sequence↗