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Biomedical subjects

M Maeda

Publications and source records attributed to M Maeda.

At least 253 records · Page 14Linked to original sources
PubMed2000

Antimetastatic and antitumor effects of 2,4-diamino-6-(pyridine-4-yl)-1,3,5-triazine (4PyDAT) on the high lung metastatic colon 26 tumor in mice.

The therapeutic potential of a diaminotriazine, 2,4-diamino-6-(pyridine-4-yl)-1,3,5-triazine (4PyDAT), was investigated in a metastatic model using the mouse colon 26 carcinoma variant (Co26Lu), which preferentially metastasizes to the lung of mouse. The compound had a moderate antimetastatic activity as well as antitumor activity, without toxicity to the host, when administered orally. In the cytotoxicity test in vitro, 4PyDAT showed very weak direct cytotoxicity against the Co26Lu cell line, Co26Lu(F55) (IC50 < or = 1000 microM). Less microcapiral formation on tumors were observed for the treated group with a hemorrhage than the control group under microscopy. 4PyDAT significantly inhibited the production of urokinase-type plasminogen activator (u-PA) in Co26Lu(F55) cells. These results suggest that the antimetastatic and antitumor activities of 4PyDAT are due in part to inhibition of angiogenesis, rather than direct antiproliferative action on the tumor cells. 4PyDAT may become a lead compound to develop antitumor triazine derivatives based on antiangiogenic action.

Animals↗
PubMed2000

[Multimodality therapy for synchronous liver metastases of gastric cancer--significance of aggressive hepatic resection of liver lesions].

We analyzed 15 gastric cancer patients with synchronous liver metastases, and studied the significance of hepatic resection with multimodality therapy. 1. Both gastric and hepatic resections followed by intra-arterial or systemic chemotherapy were performed for six patients, two of whom had intra-operative MCT or EIT. The survival time of four patients without recurrence was 5 Y 4 M, 4 Y 5 M, 2 Y 4 M and 11 M. Two patients died of recurrence in the retroperitoneum or residual liver 3 Y 10 M and 8 M after therapy, respectively. The three-year survival rate was 83%. 2. The longest survival among the five patients treated with gastric resection without hepatic resection followed by intra-arterial or systemic chemotherapy was 1 Y 1 M. 3. Four patients with non-curative factors (P, N, M) were treated with systemic chemotherapy only, and the longest survival was 1 Y 1 M. In conclusion, when local control is obtained during surgery in patients with gastric cancer with synchronous liver metastasis, aggressive hepatic resection supported with MCT or EIT should be performed on liver lesions to improve the prognosis.

Aged↗
PubMed2000

Red swamp crawfish (Procambarus clarkii): an alternative experimental host in the study of white spot syndrome virus.

The pathogenicity of white spot syndrome virus (WSSV) for the red swamp crawfish (Procambarus clarkii) was investigated after infection by intramuscular (i.m.) injection and oral route. The cumulative mortality of crawfish injected i.m. with WSSV reached 100% in 5 days. After oral feeding WSSV-infected kuruma shrimp (Penaeus japonicus) muscle tissues to the crawfish the cumulative mortality of this host reached 100% in 11 days. On reinfection trials, all the crawfish fed WSSV-infected crawfish muscle tissues died in 9 days. All the shrimp injected with a filtrate of infected crawfish heart tissues died in 12 days with typical signs of white spot syndrome (WSS). Electron microscopy clearly demonstrated that WSSV propagated in the cells of the crawfish midgut. This study showed that the red swamp crawfish can be used as alternative experimental host in the study of WSSV.

Animals↗
PubMed1999

Vasogenic edema on MELAS: a serial study with diffusion-weighted MR imaging.

The authors performed a serial study of a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like syndrome (MELAS) who presented with diffusion-weighted MRI (DWI). DWI demonstrated a higher apparent diffusion coefficient in the lesion than in the control region during the acute stage of stroke. Vasogenic edema is present in stroke-like episodes in MELAS.

Blood-Brain Barrier↗
PubMed1999

Microstructure and release characteristics of the minipellet, a collagen-based drug delivery system for controlled release of protein drugs.

We have developed the minipellet, a matrix-type system for the sustained delivery of protein drugs using collagen as a biodegradable drug carrier. In this study, we analyzed the microstructure and release profile of the minipellet containing human serum albumin (HSA) as a model drug.The findings suggest that the minipellet has a structure in which collagen fibers are strongly oriented in the direction of extrusion from the nozzle in the molding process of the minipellet, and that HSA exists as fine particulate clusters which are homogeneously distributed among the collagen fibers in the minipellet. During release, the HSA clusters dissolve and HSA is retained within the collagen matrix as a solution.The results of release experiments indicate that HSA release from the minipellet is mainly controlled by diffusion in the collagen matrix, and that sustained release is achieved by the dense structure of the collagen matrix which is formed in the manufacture process. In addition, more detailed study suggests that the minipellet has unique directional release behavior caused by its microstructure.

Collagen↗
PubMed1999

Unique recognition style of tRNA(Leu) by Haloferax volcanii leucyl-tRNA synthetase.

The recognition manner of tRNA(Leu), a class II tRNA characterized by a long variable arm, by leucyl-tRNA synthetase from an extreme halophilic archaea, Haloferax volcanii, was studied using the in vitro transcription system. It was found that the discriminator base (A73) and the long variable arm, especially the specific loop sequence A47CG47D and U47H at the base of this helix, are significant for recognition by LeuRS. An appropriate stem length of the variable arm was also required. Base substitutions in the anticodon arm did not affect the leucylation activity. Transplantation of both the discriminator base and the variable arm of tRNA(Leu) was not sufficient to introduce leucylation activity to tRNA(Ser). Insertion of an additional nucleotide into the D-loop, which is not involved in the direct interaction with LeuRS, converted tRNA(Ser) to an efficient leucine acceptor. This suggests that differences in the tertiary structure play a key role in eliminating tRNA(Ser). The sequence-specific recognition of the long variable arm of tRNA(Leu) has not been observed in any of other organisms reported, such as Escherichia coli, yeast or human. On the other hand, the mode of discrimination from non-cognate tRNAs is similar to that in E. coli in that differences in the tertiary structure play a key role. Similarity extends to the substrate stringency, exemplified by a cross-species aminoacylation study showing that no class II tRNAs from E. coli or yeast can be leucylated by H. volcanii LeuRS. Our results have implications for the understanding of the evolution of the recognition system of class II tRNA.

Acylation↗
PubMed1999

Bioconjugation of laminin-related peptide YIGSR with polyvinyl pyrrolidone increases its antimetastatic effect due to a longer plasma half-life.

Polyvinyl pyrrolidone (PVP) which can be radically synthesized and have a long blood residency was used to modify the laminin-related peptide YIGSR, and its inhibitory effect on experimental lung metastasis of B16-BL6 melanoma cells was examined. The antimetastatic effect of PVP-conjugated YIGSR (PVP-YIGSR) was more than 100-fold greater than that of native YIGSR. When injected intravenously, PVP-YIGSR showed more than a 15-fold longer plasma half-life relative to native YIGSR. In addition, the stability of YIGSR in plasma was increased by conjugation with PVP. These findings suggest that PVP is a useful polymeric modifier for increasing the antimetastatic activity of YIGSR.

Animals↗
PubMed1999

An ABC transporter homologous to TAP proteins.

Polymerase chain reaction amplification of cDNA from rat intestine revealed the expression of a novel ABC transporter, TAPL (TAP-like). Subsequently, the protein sequence was deduced from the nucleotide sequence of cDNA carrying the entire coding region. TAPL is transcribed ubiquitously in various rat tissues. The protein, with 762 amino acid residues, has potential transmembrane domains, and an ATP-binding domain in its amino and carboxyl terminal regions, respectively, and is highly homologous to TAP1 and TAP2 (transporters associated with antigen presentation/processing): pairwise comparisons with TAPL demonstrated 39 and 41% of the residues are identical, respectively. These numerical values are essentially the same as that for TAP1 and TAP2 (39%), and the hydropathy profiles of TAPL, TAP1 and TAP2 are quite similar. The similarity among these three proteins suggests that they could be derived from a common ancestral gene. Furthermore, we found that there is a potential splicing isoform, sharing the amino terminal 720 amino acid residues of TAPL.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Sterol regulatory element-binding protein negatively regulates microsomal triglyceride transfer protein gene transcription.

We herein report that mRNA expression of microsomal triglyceride transfer protein (MTP) and its protein synthesis decline in response to sterol depletion in HepG2 cells, and we functionally characterized the MTP gene promoter in an effort to investigate the molecular mechanisms by which MTP gene transcription is regulated. Luciferase assays using truncated versions of the reporter gene revealed that the region at -124 to +33 base pairs of the human promoter contains the elements required for the suppression of transcription by sterol depletion. Enforced expression of an active form of sterol regulatory element-binding protein (SREBP)-1 (amino acids 1-487) or -2 (amino acids 1-481), both of which are activated under sterol-depleted conditions, is able to mimic sterol-mediated down-regulation. Either further truncation of the promoter region or mutation of the putative SREBP-binding sequence (5'-GCAGCCCAC-3', -124 to -116 base pairs) abolishes the sterol- and SREBP-dependent transcriptional regulation. Gel mobility shift assay showed that recombinant SREBP-2-(1-481) is able to bind the sequence. Enforced expression of a truncated form of SREBP-2 (amino acids 31-481), which acts as an inhibitor of transcription of the low density lipoprotein receptor gene because it lacks the transcriptional activation domain, also diminishes the luciferase activity, suggesting that direct binding to the promoter region might be sufficient and that the mechanism by which SREBPs inhibit MTP gene expression is distinct from that for the transcriptional stimulation of sterol-regulated genes. Although the SREBP-binding site overlaps a negative insulin-responsive element, insulin negatively regulates MTP gene expression even when the amount of the active form of SREBPs is quite low under the sterol-loaded conditions, indicating that SREBPs only slightly mediate, if at all, the insulin effects. Overall, we conclude that SREBPs are responsible for regulation of lipoprotein secretion via their control of MTP gene expression. Moreover, our results describe for the first time a novel mechanism by which SREBPs negatively regulate expression of the gene encoding the protein involved in lipid metabolism.

Base Sequence↗
PubMed1999

Expression level, subcellular distribution and rho-GDI binding affinity of merlin in comparison with Ezrin/Radixin/Moesin proteins.

Merlin, a neurofibromatosis type-2 tumor suppressor, shows significant sequence similarity to ERM (Ezrin/Radixin/Moesin) proteins, general actin filament/plasma membrane cross-linkers, which are regulated in a Rho-dependent manner. To understand its physiological functions, we compared merlin with ERM proteins in vivo and in vitro. Quantitative immunoblotting revealed that the molar ratio of merlin/ERM in cultured epithelial or non-epithelial cells was approximately 0.14 or approximately 0.05, respectively. After centrifugation of cell homogenate, merlin was mostly recovered in the insoluble fraction, whereas almost half of ERM proteins were found in the soluble fraction. Merlin and ERM proteins were concentrated at microvilli when introduced into fibroblasts. In contrast, in epithelial cells, introduced merlin was co-distributed with E-cadherin in lateral membranes, whereas ERM proteins were concentrated in apical microvilli. Finally, we examined the binding affinity of merlin to Rho GDP dissociation inhibitor (Rho-GDI), to which N-terminal halves of ERM proteins but not the full-length molecules specifically bind. In vitro binding assays revealed that the N-terminal halves of merlin isoform-I and -II as well as full-length merlin isoform-II bound to Rho-GDI with similar binding affinity to ERM proteins. Immunoprecipitation confirmed these findings in vivo. These findings do not favor the notion that merlin functions simply in a redundant or competitive manner to ERM proteins.

3T3 Cells↗
PubMed1999

Scopolamine-sensitive and resistant components of increase in cerebral cortical blood flow elicited by periaqueductal gray matter of rats.

The present study attempted to evaluate the effects of inhibition of cortical muscarinic receptors on the increase in cortical blood flow (laser-Doppler flowmetry) elicited by chemical stimulation of the periaqueductal gray matter in 28 anesthetized rats with cervical cordotomy. A new device was introduced which allowed focal cortical superfusion with scopolamine, an antagonist for muscarinic receptors, without disturbing the temperature of an exposed cortical area under study. We found that although the flow increase was attenuated by scopolamine (31.6 micromol/l to 1 mmol/l) so applied, about one third of it was resistant to the treatment. Cortical muscarinic and non-muscarinic receptor mechanisms may thus subserve the mediation of the flow increase.

Animals↗
PubMed1999

Injection of antisense oligos to nNOS into nucleus tractus solitarii increases blood pressure.

We investigated the cardiovascular effects of bilateral microinjection of antisense oligodeoxynucleotides (oligos) into the nucleus tractus solitarii (NTS) to neuronal nitric oxide synthase (nNOS) to suppress the expression of nNOS molecular biologically. In urethane-anesthetized, paralyzed Wistar-Kyoto rats, bilateral microinjection of nNOS antisense oligos (20 pmol in a 50nl volume) into the NTS produced a significant increase in mean arterial blood pressure at 30-60min after injection, compared with rats injected with nNOS sense or scrambled oligos. Immunohistochemical study demonstrated that nNOS immunoreactivity in the rat NTS was suppressed by nNOS antisense oligos. These results indicate that suppression of the nNOS gene using antisense in the NTS increases blood pressure.

Animals↗
PubMed1999

Suckling defect in mice lacking the soluble haemopoietin receptor NR6.

Cytokines control a variety of cellular responses including proliferation, differentiation, survival and functional activation, via binding to specific receptors expressed on the surface of target cells [1]. The cytokine receptors of the haemopoietin family are defined by the presence of a conserved 200 amino acid extracellular domain known as the haemopoietin domain [2]. We report here the isolation of NR6, a haemopoietin receptor that, like the p40 subunit of interleukin-12 (IL-12) [3] and the EBI3 gene induced by Epstein-Barr virus infection in lymphocytes [4], contains a typical haemopoietin domain but lacks transmembrane and cytoplasmic domains. Although in situ hybridisation revealed NR6 expression at multiple sites in the developing embryo, mice lacking NR6 did not display obvious abnormalities and were born in the expected numbers. Neonatal NR6(-/-) mice failed to suckle, however, and died within 24 hours of birth, suggesting that NR6 is necessary for the recognition or processing of pheromonal signals or for the mechanics of suckling itself. In addition, NR6(-/-) mice had reduced numbers of haemopoietic progenitor cells, suggesting a potential role in the regulation of primitive haemopoiesis.

Amino Acid Sequence↗
PubMed1999

Differential expression of glutaredoxin and thioredoxin during monocytic differentiation.

Macrophages generate reactive oxygen intermediates (ROIs) as the effectors of anti-bacterial defense mechanism. Intracellular ROIs and reduction/oxidation (redox) status play crucial roles in signal transduction. We therefore investigated the expression of redox-regulating proteins such as glutaredoxin (GRX) and thioredoxin (TRX) during the differentiation of murine monocytic leukemia cell line M1 cells and human monocytic leukemia cell line U937 cells. When M1 cells were treated by IL-6, GRX mRNA markedly increased and TRX mRNA also increased slightly. In contrast, there was no increase of GRX mRNA in D-cell, which is a sub-cell line derived from M1 lacking in the capacity of differentiation. GRX mRNA also increased in U937 cells differentiated by phorbol 12-myristate 13-acetate (PMA). By immunohistochemistry, unstimulated M1 cells showed strong staining of TRX and marginal staining of GRX. In contrast, TRX expression in IL-6 treated M1 cells is as strong as in unstimulated M1 cells, whereas GRX expression is slightly enhanced in IL-6 treated M1 cells. Phagocytosis is markedly enhanced and hydrogen peroxide production is slightly enhanced in IL-6 treated M1 cells. These results showed that TRX is steadily expressed whereas GRX is induced in association with the differentiation in macrophage-like cell line cells, suggesting differential roles of these redox regulators in macrophage lineage.

Animals↗
PubMed1999

A nifS-like gene, csdB, encodes an Escherichia coli counterpart of mammalian selenocysteine lyase. Gene cloning, purification, characterization and preliminary x-ray crystallographic studies.

Selenocysteine lyase is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that catalyzes the exclusive decomposition of L-selenocysteine to L-alanine and elemental selenium. An open reading frame, named csdB, from Escherichia coli encodes a putative protein that is similar to selenocysteine lyase of pig liver and cysteine desulfurase (NifS) of Azotobacter vinelandii. In this study, the csdB gene was cloned and expressed in E. coli cells. The gene product was a homodimer with the subunit Mr of 44,439, contained 1 mol of PLP as a cofactor per mol of subunit, and catalyzed the release of Se, SO2, and S from L-selenocysteine, L-cysteine sulfinic acid, and L-cysteine, respectively, to yield L-alanine; the reactivity of the substrates decreased in this order. Although the enzyme was not specific for L-selenocysteine, the high specific activity for L-selenocysteine (5.5 units/mg compared with 0.019 units/mg for L-cysteine) supports the view that the enzyme can be regarded as an E. coli counterpart of mammalian selenocysteine lyase. We crystallized CsdB, the csdB gene product, by the hanging drop vapor diffusion method. The crystals were of suitable quality for x-ray crystallography and belonged to the tetragonal space group P43212 with unit cell dimensions of a = b = 128.1 A and c = 137.0 A. Consideration of the Matthews parameter Vm (3.19 A3/Da) accounts for the presence of a single dimer in the crystallographic asymmetric unit. A native diffraction dataset up to 2.8 A resolution was collected. This is the first crystallographic analysis of a protein of NifS/selenocysteine lyase family.

Animals↗
PubMed1999

Decrease of metastatic ability after selection for intravasating ability in Lewis lung carcinoma (3LL) cell line.

The release of cancer cells from the primary site and penetration into blood vessels are obligatory preliminary steps for metastasis. To investigate the mechanism of such steps we isolated variant cells (designated as Int-3LL) possessing enhanced intravasating ability from Lewis lung carcinoma (3LL) cells by in vivo selection. In spite of the enhanced intravasating ability of Int-3LL, the spontaneous and experimental metastatic abilities of Int-3LL decreased significantly compared to parent cells. Such a cell line has never been reported so far. The matched pair of cell lines described in this report provides a useful system for investigating the primary steps of metastasis.

Animals↗
PubMed1999

14-3-3 protein eta chain gene (YWHAH) polymorphism and its genetic association with schizophrenia.

Recent genetic analyses have suggested a linkage between schizophrenia and the chromosomal region 22q12-q13. 14-3-3 protein, abundant in the brain, mediates interactions between diverse molecules of biological activities; its gene was recently mapped to chromosome 22q12.1-q13.1. We therefore investigated allele frequencies of a variable number of tandem repeat (VNTR) in the 5'-noncoding region of the 14-3-3 eta chain gene in controls and schizophrenics. The frequencies of the two-repeat allele were significantly higher (P < 0.05) in the schizophrenics, and particularly in those with onset before age 22 (early-onset schizophrenics, P < 0.02), than in the controls. The odds ratio was significantly increased in the early-onset schizophrenics homozygous for the two-repeat allele (OR = 3.3, 95% CI = 1.1-9.7). The 14-3-3 eta chain gene is a potential susceptibility gene for schizophrenia, and particularly for early-onset schizophrenia.

14-3-3 Proteins↗