Biomedical subjects

Y Maeda

Publications and source records attributed to Y Maeda.

At least 91 records · Page 5Linked to original sources

PubMed2001

Recruitment of protein kinase D to the trans-Golgi network via the first cysteine-rich domain.

Protein kinase D (PKD) is a cytosolic protein, which upon binding to the trans-Golgi network (TGN) regulates the fission of transport carriers specifically destined to the cell surface. We have found that the first cysteine-rich domain (C1a), but not the second cysteine-rich domain (C1b), is sufficient for the binding of PKD to the TGN. Proline 155 in C1a is necessary for the recruitment of intact PKD to the TGN. Whereas C1a is sufficient to target a reporter protein to the TGN, mutation of serines 744/748 to alanines in the activation loop of intact PKD inhibits its localization to the TGN. Moreover, anti-phospho-PKD antibody, which recognizes only the activated form of PKD, recognizes the TGN-bound PKD. Thus, activation of intact PKD is important for binding to the TGN.

Amino Acid Substitution↗

PubMed2001

Quantification of TECTA and DFNA5 expression in the developing mouse cochlea.

TECTA and DFNA5 are the mouse orthologues of the human deafness-associated genes TECTA and DFNA5. To determine how expression of these genes is regulated during development, relative mRNA abundance was examined in mice by non-radioactive RT-PCR. TECTA mRNA was detected on embryonic day 15 (E15), increased to its highest level on postnatal day 3 (P3) and then dramatically decreased by P15. Low levels persisted (adulthood, P45 to 67) with mean mRNA abundance after P15 less than 25% of P3 levels. DFNA5 mRNA expression was constant throughout these time points. These results imply that TECTA is transcribed at a particularly high level during tectorial membrane morphogenesis. In contrast, DFNA5 is present in both the developing and mature cochlea.

Aging↗

PubMed2001

Discovery of X-rays from the protostellar outflow object HH2.

Herbig-Haro (HH) objects have been known for 50 years to be luminous condensations of gas in star-forming regions, but their underlying physical nature is still being elucidated. Previously suggested models encompass newborn stars, stellar winds clashing with nebular material, dense pockets of interstellar gas excited by shocks from outflows, and interstellar 'bullets' (ref. 6). Recent progress has been made with the jet-induced shock model, in which material streams out of young stellar objects and collides with the surrounding interstellar medium. A clear prediction of this model is that the most energetic Herbig-Haro objects will emit X-rays, although they have not hitherto been detected. Here we report the discovery of X-ray emission from one of the brightest and closest Herbig-Haro objects, HH2, at a level consistent with the model predictions. We conclude that this Herbig-Haro object contains shock-heated material located at or near its leading edge with a temperature of about 106 K.

Journal Article↗

PubMed2001

Pd(ii)-hydrotalcite-catalyzed oxidation of alcohols to aldehydes and ketones using atmospheric pressure of air.

A heterogenized Pd catalyst, Pd(II)-hydrotalcite (palladium(II) acetate-pyridine complex supported by hydrotalcite) catalyzes the aerobic oxidation in toluene of a variety of primary and secondary alcohols into the corresponding aldehydes and ketones in high yields using atmospheric pressure of air as a sole oxidant under mild conditions. This catalyst is also effective for the oxidation of allylic alcohols, especially such as geraniol and nerol, without any isomerization of an alkenic part. The catalyst can be easily prepared from all commercially available reagents and reused several times.

Journal Article↗

PubMed2001

MM-1, a c-Myc-binding protein, is a candidate for a tumor suppressor in leukemia/lymphoma and tongue cancer.

The c-myc oncogene product (c-Myc) is a transcription factor that dimerizes with Max and recognizes the E-box sequence, and it plays key functions in cell proliferation, differentiation, and apoptosis. We previously showed that MM-1 bound to myc box II within the transactivation domain of c-Myc and repressed the E-box-dependent transcriptional activity of c-Myc. Here we report that MM-1 showed features of a tumor suppressor. In an EST data base search for cDNAs homologous to MM-1, we found a frequent substitution of amino acid 157 of MM-1, from alanine to arginine (A157R), and the substitution was observed more in tumor cells than in normal cells. A survey of the A157R mutation of MM-1 in 57 cultured cancer cells and 90 tissues from cancer patients showed that the A157R was present in about 50-60% of leukemia/lymphoma cells and in more than 75% of squamous cell carcinoma of tongue cancer. Although both the A157R and the wild-type MM-1 bound to c-Myc, only A157R lost the activities to repress both the E-box-dependent transcriptional activity of c-Myc and the myc/ras cooperative transforming activity in rat 3Y1 cells. Furthermore, the wild-type MM-1, but not A157R, arrested the growth of 3Y1 cells. The human MM-1 gene was mapped at chromosome 12q12-12q13, where many chromosome abnormalities in cancer cells have been reported. The results suggest that MM-1 is a novel candidate for a tumor suppressor that controls the transcriptional activity of c-Myc.

3T3 Cells↗

PubMed2001

Rapid X-ray flaring from the direction of the supermassive black hole at the Galactic Centre.

The nuclei of most galaxies are now believed to harbour supermassive black holes. The motions of stars in the central few light years of our Milky Way Galaxy indicate the presence of a dark object with a mass of about 2.6 x 106 solar masses (refs 2, 3). This object is spatially coincident with the compact radio source Sagittarius A* (Sgr A*) at the dynamical centre of the Galaxy, and the radio emission is thought to be powered by the gravitational potential energy released by matter as it accretes onto a supermassive black hole. Sgr A* is, however, much fainter than expected at all wavelengths, especially in X-rays, which has cast some doubt on this model. The first strong evidence for X-ray emission was found only recently. Here we report the discovery of rapid X-ray flaring from the direction of Sgr A*, which, together with the previously reported steady X-ray emission, provides compelling evidence that the emission is coming from the accretion of gas onto a supermassive black hole at the Galactic Centre.

Journal Article↗

PubMed2001

Proliferating oligodendrocytes are present in both active and chronic inactive multiple sclerosis plaques.

The proliferation marker Ki-67 labels cell nuclei in the G(1), S, M, and G(2) phases of the cell cycle. We used Ki-67 immunohistochemistry to quantify proliferating glial cells in brain tissue sections from twenty-four patients, comprised of multiple sclerosis, normal brains, and other neurological disease controls. Glial proliferation was greatly increased in MS lesions when compared with control brain white matter. Both actively demyelinating/early remyelinating plaques and chronic inactive plaques of long standing often displayed large numbers of glial cells in the proliferative cycle. The bulk of these proliferating cells were of oligodendroglial lineage in the MS plaques. Ki-67 positive macrophage/microglial lineage cells were largely restricted to acute lesions. The finding of increased numbers of proliferating oligodendroglia in most MS plaques, regardless of disease duration or activity state, indicates that the MS brain is capable of recruiting unexpectedly large numbers of new oligodendrocytes over long periods of time. The factors within the MS plaque microenvironment that provoke new oligodendrocyte generation and their subsequent loss still need to be identified.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

PubMed2001

Origin of the hard x-ray emission from the Galactic plane.

The Galactic plane is a strong emitter of hard x-rays (2 to 10 kiloelectron volts), and the emission forms a narrow continuous ridge. The currently known hard x-ray sources are far too few to explain the ridge x-ray emission, and the fundamental question of whether the ridge emission is ultimately resolved into numerous dimmer discrete sources or truly diffuse emission has not yet been settled. In order to obtain a decisive answer, using the Chandra X-ray Observatory, we carried out the deepest hard x-ray survey of a Galactic plane region that is devoid of known x-ray point sources. We detected at least 36 new hard x-ray point sources in addition to strong diffuse emission within a 17' by 17' field of view. The surface density of the point sources is comparable to that at high Galactic latitudes after the effects of Galactic absorption are considered. Therefore, most of these point sources are probably extragalactic, presumably active galaxies seen through the Galactic disk. The Galactic ridge hard x-ray emission is diffuse, which indicates omnipresence within the Galactic plane of a hot plasma, the energy density of which is more than one order of magnitude higher than any other substance in the interstellar space.

Journal Article↗

PubMed2001

Formation and emission of volatile polonium compound by microbial activity and polonium methylation with methylcobalamin.

We observed biologically mediated emission of Po from culture solution inoculated sea sediment extract and incubated under natural light/dark cycle condition or dark condition the emitted Po compound would be lipophilic because of effective collection in organic solvent. Sterilization of the culture medium with antibiotics or CuSO4 completely suppressed growth of microorganisms and resulted in no emission of Po, indicating biological activity of microorganisms is responsible for formation and emission of volatile Po compound. Po emission also occurred when seawater was used as a culture medium. Our finding indicates a possibility of biotic source for atmospheric Po in the environment, which has been believed to be originated from abiotic sources. We compared emission behavior of Po and S in the culture experiments, the elements belong to XVI group in the Periodical Table, and consider that their emission mechanisms involved would be different though the emission of both elements is supported by biological activity of microorganisms. One of the chemical forms of S emitted was confirmed to be dimethyl sulfide (DMS) but that of Po is not known. Methylation experiments of Po with methylcobalamin demonstrated a formation and emission of volatile Po compound. The methylation of Po with methylcobalamin might be related to the observed Po emission in the culture experiments.

Air Pollutants↗

PubMed2001

Target genes downregulated by the BCL-6/LAZ3 oncoprotein in mouse Ba/F3 cells.

The BCL-6/LAZ3 gene encodes a zinc-finger transcriptional repressor and is located at the breakpoint of the 3q27-associated translocations that occur most frequently in non-Hodgkin's lymphomas (NHLs). A number of chromosomal translocations involving BCL-6 have been analyzed, but the biological functions of this protein remain obscure. To examine cell responses and target genes related to the BCL-6 signaling pathway, we established Ba/F3 pro-B cells carrying a human BCL-6 transgene that is inducible under control of the lactose operon. Using a cDNA array hybridization technique, we found that the induced BCL-6 protein can downregulate the expressions of the genes, cyclin A2, chemokine receptor CXCR4, and insulin-like growth factor binding protein-4 (IGFBP-4) in the Ba/F3 cells. Northern blot analysis established that the expressions of these genes were indeed downregulated by the induced BCL-6 protein but in a somewhat different manner. The induced BCL-6 protein also inhibited cell proliferation of Ba/F3 cells. These findings strongly suggest that three key genes, namely cyclin A2, CXCR4, and IGFBP-4 may play a role in the downstream of the BCL-6 signaling pathway during B-lymphoid differentiation.

Animals↗

PubMed2001

Enhanced infection of an X4 strain of HIV-1 due to capping and colocalization of CD4 and CXCR4 induced by capsianoside G, a diterpene glycoside.

We investigated whether capsianosides, diterpene glycosides, extracted from Capsicum plants could affect human immunodeficiency virus type 1 (HIV-1) infection. Significant effect on virus infection in MAGI/CCR5 cells was neither observed for the X4 virus by capsianosides II, XI, and A, nor for an R5 virus by capsianoside G. Apparent enhancement of X4 HIV-1 infection by capsianoside G was observed and exclusively related to the usage of the CXCR4 coreceptor. The capsianoside G-treated cells had no change in the expression level of CD4, CXCR4, and CCR5, however, colocalization and capping of CD4 and CXCR4, but not of CD4 and CCR5 was observed. Our results suggested that capsianoside G enhanced X4 virus infection at the level of viral penetration through the capping and colocalization of receptors needed for infection.

Adsorption↗

PubMed2001

The complete nucleotide sequence of a plant root-inducing (Ri) plasmid indicates its chimeric structure and evolutionary relationship between tumor-inducing (Ti) and symbiotic (Sym) plasmids in Rhizobiaceae.

The Ri (root-inducing) plasmid in Agrobacterium rhizogenes and Ti (tumor-inducing) plasmid in Agrobacterium tumefaciens have provided the fundamental basis for the construction of plant vectors and transgenic plants. Recently, the determination of the first complete nucleotide sequence of the Ti plasmid (pTi-SAKURA) has been successful. To understand the general structure of these oncogenic T-DNA transfer plasmids, the whole nucleotide sequence of a mikimopine-type Ri plasmid, pRi1724, was analyzed. The plasmid is 217,594 bp in size, and has 173 open reading frames (ORFs) in total, which are asymmetrically distributed. Except for 27 ORFs, which are unknown, 173 ORFs were classified into 12 groups as follows: three for DNA replication, nine for plasmid modification, 22 for conjugation, 26 for virulence, 11 for T-DNA gene, 19 for mikimopine/mikimopine-lactam transport, ten for an unknown opine metabolism, seven for transcriptional regulator, five for sugar transport, five for glycerol metabolism, four for chemoreceptor and 32 for others. The elucidated chimeric structure of pRi1724 interestingly indicates that the evolution of Rhizobiaceae plasmids seems to have kept interactions among the plasmids; especially, the genes and elements for a conjugal transfer of pRi1724 had clearly closer kinship to those of a Sym (symbiotic) plasmid, pNGR234a in Rhizobium sp. than those of Ti plasmids. By using sequencing and Northern analysis, we examined the metabolic pathway and gene expression of mikimopine, which is probably an Ri-specific opine.

ATP-Binding Cassette Transporters↗

PubMed2001

Regulation of cardiomyocyte mechanotransduction by the cardiac cycle.

BACKGROUND: Overloading the left ventricle in systole (pressure overload) is associated with a distinct morphological response compared with overload in diastole (volume overload). METHODS AND RESULTS: We designed a novel computer-controlled experimental system that interfaces biaxially uniform strain with electrical pacing, so that cellular deformation can be imposed during a specified phase of the cardiac cycle. Cardiomyocytes were exposed to strain (4%) during either the first third (systolic phase) or last third (diastolic phase) of the cardiac cycle. Strain imposed during the systolic phase selectively activated p44/42 mitogen-activated protein kinase (MAPK) and MAPK/extracellular signal-regulated protein kinase kinase (MEK1/2, an activator of p44/42 MAPK) compared with strain imposed during the diastolic phase. In contrast, there was no difference in activation of p38 and c-Jun NH(2)-terminal kinases induced by strain imposed during the systolic phase (5.8- and 3.3-fold versus control, n=4) compared with the diastolic phase (5.5- and 3.1-fold). Induction of both brain natriuretic peptide (5.8-fold versus control, P:<0.05, n=3) and tenascin-C (7.0-fold, P:<0.02) mRNA expression by strain imposed during the systolic phase was greater than during the diastolic phase (3.9- and 3.6-fold, respectively). [(3)H]leucine incorporation induced by strain imposed during the systolic phase (4.0-fold versus control) was greater than during the diastolic phase (2.7-fold, P:<0.02, n=4); a selective inhibitor of MEK1/2 inhibited this difference. CONCLUSIONS: Mechanical activation of p44/42 MAPK and MEK1/2, gene expression, and protein synthesis is regulated by the cardiac cycle, suggesting that mechanotransduction at the cellular level may underlie differences between pressure and volume overload of the heart.

Animals↗

PubMed2001

Local structure of Ge nanocrystals embedded in SiO2 studied by X-ray absorption fine structure.

Local structure of Ge nanocrystals embedded in SiO2 has been studied by X-ray absorption fine structure on the Ge K-edge. The XANES and EXAFS results indicate that Ge atoms in samples with the Ge concentration x=25-40 mol. % are coordinated with oxygen atoms, while they exist as amorphous Ge clusters in samples with x=60 mol. %. Upon annealing, completely relaxed crystalline Ge phase is formed for samples with x=60 mol. %, in contrast to the x=25-40 mol. % sample, which show little or no indication of Ge cluster formation. A possible mechanism of Ge nanocluster formation is discussed.

Journal Article↗

PubMed2001

Sonochemical degradation of chlorinated hydrocarbons using a batch and continuous flow system.

The sonochemical degradation of chlorinated hydrocarbons such as 1,1,1-trichloroethane, trichloroethylene and tetrachloroethylene in aqueous solution was carried out in the batch and continuous flow systems at an ultrasonic frequency of 100kHz under an air atmosphere. In the batch experiment, the rate of degradation follows the order 1,1,1-trichloroethane>tetrachloroethylene>trichloroethylene, and the chlorinated hydrocarbon were readily degraded by ultrasonic irradiation. The experiments in the continuous flow system were performed in the range of volumetric flow rate from 7 to 30 x 10(-3)lmin(-1). The conversion of the chlorinated hydrocarbons at a steady-state of reactor depended on the volumetric flow rate. The yield of Cl(-) (as a measurement of mineralization of chlorinated hydrocarbons) was 70-90% of the chlorine atoms in the parent chlorinated hydrocarbon molecules. From the viewpoint of the scale-up process, the sonochemical degradation of trichloroethylene was simulated in a three stage reactor, and the conversion (>99%) in a third stage reactor was showed the good results that can be satisfied a desired water quality standard.

Environmental Pollution↗

PubMed2001

Protein kinase D regulates the fission of cell surface destined transport carriers from the trans-Golgi network.

When a kinase inactive form of Protein Kinase D (PKD-K618N) was expressed in HeLa cells, it localized to the trans-Golgi network (TGN) and caused extensive tubulation. Cargo that was destined for the plasma membrane was found in PKD-K618N-containing tubes but the tubes did not detach from the TGN. As a result, the transfer of cargo from TGN to the plasma membrane was inhibited. We have also demonstrated the formation and subsequent detachment of cargo-containing tubes from the TGN in cells stably expressing low levels of PKD-K618N. Our results suggest that PKD regulates the fission from the TGN of transport carriers that are en route to the cell surface.

Biological Transport↗

PubMed2001

Phosphatidylglycerol participates in syncytium formation induced by HTLV type 1-bearing cells.

We previously reported that 71-kDa heat shock cognate protein (HSC70) was expressed on the cell surface of human T cell lymphotropic virus type 1 (HTLV-1)-susceptible cells and that HSC70, beta-actin, and a lipid-like component on the target cell membrane participated in syncytium formation by HTLV-1. We have now identified this lipid-like component to be palmitoyl (16:0)-oleoyl (18:1)-phosphatidylglycerol (POPG), using preparative thin-layer chromatographic fractionation and tandem mass spectrometric analysis. In the syncytium formation assay, exogenously added PG inhibited cell-to-cell transmission of HTLV-1 in a dose-dependent manner. Other phospholipids showed less (PE) or no effect (PC, PS, PI, PA, lysoPC, lysoPE, and CL). Binding experiments showed that PG interacted with three synthetic peptides, gp46--111, gp46--197, and gp21--400, which correspond to regions Lys111--Asp138 and Asp197--Leu216 on the gp46 surface glycoprotein, and to region Cys400--Leu429 on the gp21 transmembrane glycoprotein, respectively, as well as with intact gp46 and gp21 proteins of HTLV-1. On the other hand, HSC70 and beta-actin interacted with gp46--197 and gp46, not with gp46--111. However, the eluate from an affinity column coupled with gp46--111 contained not only PG but also HSC70 and beta-actin, despite the lack of direct interaction between gp46--111 and these proteins. In the in vitro binding assay, HSC70 showed interaction with both PG and beta-actin, while there was no evidence of any interaction between PG and beta-actin. These results suggest that HSC70 molecules on target cell surface interact with both PG in lipid bilayers and intracellular beta-actin and that these three cellular components form a receptor complex that plays a critical role in syncytium formation induced by HTLV-1-bearing cells.

Actins↗

PubMed2001

PIG-M transfers the first mannose to glycosylphosphatidylinositol on the lumenal side of the ER.

Glycosylphosphatidylinositol (GPI) acts as a membrane anchor of many cell surface proteins. Its structure and biosynthetic pathway are generally conserved among eukaryotic organisms, with a number of differences. In particular, mammalian and protozoan mannosyltransferases needed for addition of the first mannose (GPI-MT-I) have different substrate specificities and are targets of species- specific inhibitors of GPI biosynthesis. GPI-MT-I, however, has not been molecularly characterized. Characterization of GPI-MT-I would also help to clarify the topology of GPI biosynthesis. Here, we report a human cell line defective in GPI-MT-I and the gene responsible, PIG-M. PIG-M encodes a new type of mannosyltransferase of 423 amino acids, bearing multiple transmembrane domains. PIG-M has a functionally important DXD motif, a characteristic of many glycosyltransferases, within a domain facing the lumen of the endoplasmic reticulum (ER), indicating that transfer of the first mannose to GPI occurs on the lumenal side of the ER membrane.

Amino Acid Sequence↗