Biomedical subjects

M Ikeda

Publications and source records attributed to M Ikeda.

At least 415 records · Page 23Linked to original sources

PubMed1999

Large-Scale Mapping Observations of the C i (3P1-3P0) and CO (J = 3-2) Lines toward the Orion A Molecular Cloud.

Large-scale mapping observations of the 3P1-3P0 fine-structure transition of atomic carbon (C i, 492 GHz) and the J=3-2 transition of CO (346 GHz) toward the Orion A molecular cloud have been carried out with the Mount Fuji submillimeter-wave telescope. The observations cover 9 deg2 and include the Orion Nebula M42 and the L1641 dark cloud complex. The C i emission extends over almost the entire region of the Orion A cloud and is surprisingly similar to that of 13CO (J=1-0). The CO (J=3-2) emission shows a more featureless and extended distribution than C i. The C i/CO (J=3-2) integrated intensity ratio shows a spatial gradient running from the north (0.10) to the south (1.2) of the Orion A cloud, which we interpret as a consequence of the temperature gradient. On the other hand, the C i/13CO (J=1-0) intensity ratio shows no systematic gradient. We have found a good correlation between the C i and 13CO (J=1-0) intensities over the Orion A cloud. This result is discussed on the basis of photodissociation region models.

Journal Article↗

PubMed1999

Purified group X secretory phospholipase A(2) induced prominent release of arachidonic acid from human myeloid leukemia cells.

Group X secretory phospholipase A(2) (sPLA(2)-X) possesses several structural features characteristic of both group IB and IIA sPLA(2)s (sPLA(2)-IB and -IIA) and is postulated to be involved in inflammatory responses owing to its restricted expression in the spleen and thymus. Here, we report the purification of human recombinant COOH-terminal His-tagged sPLA(2)-X, the preparation of its antibody, and the purification of native sPLA(2)-X. The affinity-purified sPLA(2)-X protein migrated as various molecular species of 13-18 kDa on SDS-polyacrylamide gels, and N-glycosidase F treatment caused shifts to the 13- and 14-kDa bands. NH(2)-terminal amino acid sequencing analysis revealed that the 13-kDa form is a putative mature sPLA(2)-X and the 14-kDa protein possesses a propeptide of 11 amino acid residues attached at the NH(2) termini of the mature protein. Separation with reverse-phase high performance liquid chromatography revealed that N-linked carbohydrates are not required for the enzymatic activity and pro-sPLA(2)-X has a relatively weak potency compared with the mature protein. The mature sPLA(2)-X induced the release of arachidonic acid from phosphatidylcholine more efficiently than other human sPLA(2) groups (IB, IIA, IID, and V) and elicited a prompt and marked release of arachidonic acid from human monocytic THP-1 cells compared with sPLA(2)-IB and -IIA with concomitant production of prostaglandin E(2). A prominent release of arachidonic acid was also observed in sPLA(2)-X-treated human U937 and HL60 cells. Immunohistochemical analysis of human lung preparations revealed its expression in alveolar epithelial cells. These results indicate that human sPLA(2)-X is a unique N-glycosylated sPLA(2) that releases arachidonic acid from human myeloid leukemia cells more efficiently than sPLA(2)-IB and -IIA.

Animals↗

PubMed1999

Saccharomyces cerevisiae cultured under aerobic and anaerobic conditions: air-level oxygen stress and protection against stress.

Cells of Saccharomyces cerevisiae were grown aerobically and anaerobically, and levels of the protective compounds, cysteine and glutathione, and activities of defensive enzymes, catalase and superoxide dismutase, against an oxygen stress were determined and compared in both cells. Aerobiosis increased both the compounds and enzyme activities. The elevated synthesis of glutathione could be associated with the increased levels of cysteine which in its turn was found to be controlled by the oxygen-dependent activation of cystathionine beta-synthase.

Aerobiosis↗

PubMed1999

NH2-terminal pentapeptide of endothelial interleukin 8 is responsible for the induction of apoptosis in leukemic cells and has an antitumor effect in vivo.

We have reported that endothelial interleukin 8 (IL-8) induces apoptosis in leukemic cells in vitro and in vivo, and that interaction between endothelial cells and leukemic cells causes induction of apoptosis through the release of endothelial IL-8 (Y. Terui et al., Biochem. Biophys. Res. Commun., 243: 407-411, 1998; Y. Terui et al., Blood, 92: 2672-2680, 1998). Here, we examined whether a pentapeptide corresponding to the NH2-terminal region of endothelial IL-8 can induce apoptosis in leukemic cells. The NH2-terminal pentapeptide Ala-Val-Leu-Pro-Arg (AVLPR) was found to significantly induce apoptosis in the leukemic cell lines K562, HL-60, Jurkat, and Daudi, as compared with the COOH-terminal pentapeptide Arg-Glu-Ala-Asn-Ser (REANS). Moreover, the NH2-terminal pentapeptide AVLPR significantly inhibited growth of i.p. and s.c. tumor masses of K562 cells and induced apoptosis in these cells in vivo. The active site of endothelial IL-8 is the NH2-terminal pentapeptide AVLPR, and this may serve as a new therapy for hematological malignancies.

Animals↗

PubMed1999

Mice lacking both presenilin genes exhibit early embryonic patterning defects.

Genetic studies in worms, flies, and humans have implicated the presenilins in the regulation of the Notch signaling pathway and in the pathogenesis of Alzheimer's Disease. There are two highly homologous presenilin genes in mammals, presenilin 1 (PS1) and presenilin 2 (PS2). In mice, inactivation of PS1 leads to developmental defects that culminate in a perinatal lethality. To test the possibility that the late lethality of PS1-null mice reflects genetic redundancy of the presenilins, we have generated PS2-null mice by gene targeting, and subsequently, PS1/PS2 double-null mice. Mice homozygous for a targeted null mutation in PS2 exhibit no obvious defects; however, loss of PS2 on a PS1-null background leads to embryonic lethality at embryonic day 9.5. Embryos lacking both presenilins, and surprisingly, those carrying only a single copy of PS2 on a PS1-null background, exhibit multiple early patterning defects, including lack of somite segmentation, disorganization of the trunk ventral neural tube, midbrain mesenchyme cell loss, anterior neuropore closure delays, and abnormal heart and second branchial arch development. In addition, Delta like-1 (Dll1) and Hes-5, two genes that lie downstream in the Notch pathway, were misexpressed in presenilin double-null embryos: Hes-5 expression was undetectable in these mice, whereas Dll1 was expressed ectopically in the neural tube and brain of double-null embryos. We conclude that the presenilins play a widespread role in embryogenesis, that there is a functional redundancy between PS1 and PS2, and that both vertebrate presenilins, like their invertebrate homologs, are essential for Notch signaling.

Animals↗

PubMed1999

Beta(2)-microglobulin identified as an apoptosis-inducing factor and its characterization.

Major histocompatibility complex (MHC) molecules play an important role in antigen presentation for induction of tumor as well as cellular and humoral immunities. Recent studies using anti-MHC antibodies demonstrated that antibodies specific for HLA class I molecules induced cellular activation and a type of apoptosis that may be distinct from Fas-dependent or TNFR (tumor necrosis factor-alpha receptor)-dependent processes. We purified a previously untested apoptosis-inducing factor from HL-60 human leukemic cell-conditioned media to homogeneity and sequenced it. It was identified as beta(2)-microglobulin (beta(2)m), which has been previously known as thymotaxin and is a part of the HLA class I antigen complex. beta(2)m acts on both T-leukemic cells and myeloid leukemic cells to induce apoptosis, which then activates caspase 1 and 3. Cross-linking studies showed that biotinilated beta(2)m recognized an epitope distinct from those recognized by the anti-HLA class I antibody, as reported previously. We demonstrated that beta(2)m plays a previously unrecognized and important role in regulating the elimination of tumor cells, which occurs as a result of the action of beta(2)m as an apoptosis-inducing factor.

Amino Acid Chloromethyl Ketones↗

PubMed1999

Effect of polymer/basic drug interactions on the two-stage diffusion-controlled release from a poly(L-lactic acid) matrix.

We investigated the effect of drug physico-chemical properties on the release of basic drugs from poly(L-lactic acid) (P(L)LA) cylindrical matrices (rods; 10 mmx1 mm diameter). All the rods were revealed to exhibit two-stage diffusion-controlled release profiles resulting from the transformation of P(L)LA from an amorphous to a semicrystalline state in aqueous medium. On the assumption that interactions between polymer carboxyl residues and basic drugs control the drug release rate, we evaluated the strength of these interactions by the drug partition between the polymer and the aqueous medium. In the first release stage, the drugs diffused through the swollen polymer matrix. The polymer-drug interactions shielded the polymer terminal carboxyl residues, thereby resulting in a less hydrated matrix and consequent diminishment of drug diffusion. In the second release stage, the drugs diffused through the water-filled micropores which had developed as a result of polymer crystallization. The stronger polymer-basic drug interactions reduced the drug diffusion rate by decreasing not only the porosity of the matrix, but also the drug partition to the water-filled micropores. It was also found that the fractional drug release rate in the second stage increased with drug content of the rod at the pH where both the polymer carboxyl residues and the drugs were ionized. Since the polymer-drug interactions must be close to saturation with increasing drug content, we believe this result to be due to an increase in the ratio of the drug partition to the water-filled micropores.

Biocompatible Materials↗

PubMed1999

Alleic variants of human melatonin 1a receptor: function and prevalence in subjects with circadian rhythm sleep disorders.

The human melatonin 1a (hMella) receptor gene was screened for mutations using genomic DNA samples from patients with circadian rhythm sleep disorders and control subjects by single strand conformational polymorphism analysis (SSCP). We found seven mutations, two of which predict amino acid changes R54W and A157V, respectively. The prevalence of the R54W variant and that of the A157V variant were several times more common in non-24-h sleep-wake syndrome subjects than among control subjects, although the incidence was not significant in our study group. When expressed in COS-7 cells, the R54W mutant receptor exhibited significantly reduced B(max) and slightly enhanced affinity (reduced K(d)) compared to the wild type receptor, while the A157V variant receptor showed similar binding characteristics to the wild type. The identification of variants in the hMella receptor will provide a useful tool for analyzing genetic predisposition toward various diseases related to melatonin function and to clarify the physiological role of melatonin receptors in humans.

Alleles↗

PubMed1999

Solvents in urine as exposure markers.

Possible pitfalls and solutions are reviewed in the development and application of the methods of urinalysis for organic solvent as a biological exposure marker. In case head-space gas chromatography (HS-GC) is applied for analysis, loss of the solvent in the urine sample should be below 5% if the transfer of the sample into a HS GC vial is terminated in 5 min. When urine samples are stored in a bottle, organic solvent may partly move into the air phase in the bottle, but such loss from the water phase can be compensated by calculation, when the volumes of the air and water phases are available. Solvents in urine generally show closer correlation with the exposure intensity than the corresponding metabolite(s). When the lowest vapor exposure concentration was determined as the concentration at which the exposed subjects can be statistically separated from the non-exposed, solvent in urine can separate at a lower exposure concentration than its metabolite(s). Compared with the solvent in blood, however, solvent in urine correlates less closer to the solvent vapor exposure, especially when the vapor concentration is low, e.g. < 10 ppm toluene.

Air Pollutants, Occupational↗

PubMed1999

Background exposure of general women populations in Japan to cadmium in the environment and possible health effects.

1. The surveys were conducted in 1990s on 470 non-smoking adult women [with no specific exposure to cadmium (Cd)] in 22 sites in six regions in Japan. 2. It was found that the dietary Cd intake (as a grand geometric mean) was 25.9 microg/day, the Cd level in blood was 2.1 microg/l, and Cd level in urine was 2.1 microg/g creat. 3. Cd in rice contributed about 30% of total dietary Cd intake. 4. There was a substantial reduction in Cd burden when compared with observation in 1980s. 5. Effects on kidney functions were essentially negative when evaluated in terms of beta2-microglobulin (beta2-MG), but might be positive when alpha1-microglobulin (alpha1-MG) was evaluated; further studies are apparently necessary. 6. No effects on liver functions were detected.

Adult↗

PubMed1999

Exposure of citizens in China and in Japan to lead and cadmium: a comparative study.

To compare the background exposure of general urban populations to lead (Pb) and cadmium (Cd) in China and Japan, 250 adult women in five Chinese cities and 72 women in three Japanese cities were surveyed by means of collection and analyses of food duplicate and blood samples. The results show that the geometric mean dietary Pb intake and Pb level in blood were significantly higher among Chinese (24.6 microg/day and 45.8 ng/ml) than their counterparts in Japan (14.6 microg/day and 32.2 ng/ml). In contrast, Cd exposures were significantly higher among Japanese women (34.1 microg/day and 1.91 ng/ml) than among Chinese women (8.8 microg/day and 0.61 ng/ml). Thus, the public health concern should be focussed on Pb exposure for Chinese population and Cd for Japanese people.

Adult↗

PubMed1999

Evaluation of urinary cadmium and lead as markers of background exposure of middle-aged women in Korea: dietary intake as an influential factor.

The study was conducted to examine the validity of urinary cadmium (Cd) and lead (Pb) in comparison with the metals in blood as a biological marker of non-occupational exposure of general populations. Participants in four survey sites in Korea (107 non-smoking Korean women aged 30-49 years) offered peripheral blood, morning spot urine, and 24-h total food duplicate samples. Analysis of Cd and Pb was accomplished by graphite furnace atomic absorption spectrophotometry. The analyse levels were evaluated on an individual basis (n = 107) and also on a survey site basis, i.e. in terms of geometric means for the groups in the survey sites (n = 4). Cd in urine (as observed, or after correction for creatinine concentration or a specific gravity) correlated with Cd in blood on an individual as well as survey site basis, and tended to correlate with Cd in food duplicates on the survey site basis. Correlation of Pb in urine with Pb in blood was weaker than that of Cd in urine with Cd in blood both on the individual and survey site basis. Pb in urine correlated with Pb in food duplicates either weakly or even negatively when examined on a survey site basis. It was concluded that Cd in urine can be most probably employed as a biological marker of environmental Cd exposure of general population, whereas less support was obtained for Pb in urine as an exposure marker.

Adult↗

PubMed1999

Cell cycle-dependent switch of up-and down-regulation of human hsp70 gene expression by interaction between c-Myc and CBF/NF-Y.

A CCAAT box-binding protein subunit, CBF-C/NF-YC, was cloned as a protein involved in the c-Myc complex formed on the G(1)-specific enhancer in the human hsp70 gene. CBF-C/NF-YC directly bound to c-Myc in vitro and in vivo in cultured cells. The CBF/NF-Y.c-Myc complex required the HSP-MYC-B element as well as CCAAT in the hsp70 G(1)-enhancer, while the purified CBF subunits recognized only CCAAT even in the presence of c-Myc. Both the HSP-MYC-B and CCAAT elements were also required for the enhancer activity. In transient transfection experiments, the CBF/NF-Y.c-Myc complex, as well as transcription due to the G(1)-enhancer, was increased by the introduction of c-Myc at low doses but decreased at high doses. The repression of both complex formation and transcription by c-Myc at high doses was abrogated by the introduction of CBF/NF-Y in a dose-dependent manner. Furthermore, the CBF/NF-Y.c-Myc complex bound to the G(1)-enhancer appeared in the early G(1) phase of the cell cycle when c-Myc was not higly expressed and gradually disappeared after the c-Myc expression reached its maximum. The results indicate that the cell cycle-dependent expression of the hsp70 gene is regulated by the intracellular amount of c-Myc through the complex formation states between CBF/NF-Y and c-Myc.

3T3 Cells↗

PubMed1999

Circadian rhythms and light responsiveness of mammalian clock gene, Clock and BMAL1, transcripts in the rat retina.

Circadian expression and light-responsiveness of the mammalian clock genes, Clock and BMAL1, in the rat retina were examined by in situ hydbribization under constant darkness. A small but significant daily variation was detected in the Clock transcript level, but not in BMAL1. Light increased the Clock and BMAL1 expressions significantly when examined 60 min after exposure. The light-induced gene expression was phase-dependent for Clock and peaked at ZT2, while rather constant throughout the day for BMAL1. These findings suggest that Clock and BMAL1 play different roles in the generation of circadian rhytm in the retina from those in the suprachiasmatic nucleus. Different roles are also suggested between the two genes in the photic signal transduction in the retina.

ARNTL Transcription Factors↗

PubMed1999

Mechanism of drug release from poly(L-lactic acid) matrix containing acidic or neutral drugs.

The release profiles of acidic and neutral drugs from poly(L-lactic acid) [P(L)LA] matrices were investigated to reveal their release mechanism. Cylindrical matrices (rods; 10 mmx1 mm diameter) were prepared by the heat compression method. The acidic and neutral drugs investigated were dissolved in the P(L)LA rods. It was found that the release profiles consisted of two sequential stages. At the first release stage, P(L)LA remained in an amorphous state and the drugs diffused through the hydrated matrices. At the second release stage, P(L)LA transformed to a semicrystalline state and the drugs diffused through water-filled micropores developed by polymer crystallization. In addition, the drugs were also found to precipitate out as crystals in the rods, resulting in a transformation of the rods into drug-dispersed matrices. On the basis of these findings, we derived a modified diffusion equation for the drug release at the second stage. This equation showed good fits to the release profiles of these drugs. Furthermore, the availability of the derived equation was supported by the acceleration in the fractional drug release rate noted both with decreases in the drug content in the rod and increases in the pH of the medium.

Biodegradation, Environmental↗

PubMed1999

Characterization of three splice variants and genomic organization of the mouse BMAL1 gene.

The BMAL1 gene encodes a member of the basic helix-loop-helix/PER-ARNT-SIM (bHLH/PAS) family of transcription factors. It is a key regulator of circadian rhythms. Using sequence information from human BMAL1 (hBMAL1) cDNAs previously reported by our laboratory, we have isolated and characterized cDNAs encoding three splice variants of the mouse BMAL1 (mBMAL1) gene. Of the three splice variants, mBMAL1b extends for 1878 bp in the coding sequence, which is 91% identical to that of hBMAL1b; its deduced amino acid sequence is 626 residues long and is 98% identical to that of hBMAL1b, and sequence identities in the bHLH, PAS-A, and PAS-B regions are 98, 100, and 100%, respectively. mBMAL1b' arises from alternative usage of exon 2, which results in a 7-amino-acid insertion and alternative splice acceptor usage at the intron 9/exon 10 splice junction, which causes an alanine residue deletion. mBMAL1b' encodes 632 amino acids and contains the bHLH/PAS domains. mBMAL1g' is generated by alternative splice acceptor usage at the intron 6/exon 7 splice junction, which results in a 28-bp deletion adjacent to the 5' end of the PAS domain. Since the 28-bp deletion shifts the reading frame, mBMAL1g' is predicted to encode a product of only 222 amino acids that lacks the PAS domain. The tissue distributions of the three splice variants showed some variation. The variations in the tissue distributions and predicted amino acid sequences suggest that the three splice variants may have different functions. Direct sequencing of the genomic mBMAL1 clones indicated that the coding sequence of mBMAL1 spans 32 kb and includes 17 exons. An unusual exon/intron donor sequence was found in intron 14, which begins with GC at the 5' end. Comparison with the bHLH/PAS family genes revealed that the intron/exon splice pattern of mBMAL1 most closely matches that of the mAhr, which suggests that BMAL1 and Ahr belong to the same subclass and may be derived from a common primordial gene.

ARNTL Transcription Factors↗

PubMed1999

Mossy fiber sprouting in the dentate gyrus in a newly developed epileptic mutant, Ihara epileptic rat.

We examined the correlation between seizure activity and development of mossy fiber sprouting in the hippocampal formation using Timm staining in a newly developed Ihara epileptic rat (IER). The sprouting of mossy fibers were clearly shown in the inner molecular portion of the dentate gyrus and in the stratum oriens of CA3 pyramidal cell layer with repeated seizures. A positive correlation between the frequency of generalized tonic and clonic convulsions and the Timm staining score in molecular layer of dentate gyrus was revealed. Sprouting of mossy fiber in IER seems to be linked with seizure activities resulting from epileptic bursts, not to the genetic mutation.

Animals↗

PubMed1999

Inhibitory effect of microfibril wheat bran on azoxymethane-induced colon carcinogenesis in CF1 mice.

Microfibril wheat bran (MFW), a processed dietary fiber prepared by milling of coarse wheat bran (WB), is softer and has a more pleasant taste than WB. In this study, we examined the inhibitory effect of MFW on azoxymethane (AOM)-induced colon carcinogenesis in female CF1 mice and compared its effect with that of WB and cellulose (CL). The mice were fed a modified AIN 76 A diet supplemented with either MFW, WB, or CL at a final concentration of 20% (w/w). Six weekly s.c. injections of AOM (10 mg/kg body weight) were administered per mouse commencing 1 week after the start of the feeding period. Control mice were injected with saline only. Thirty-three weeks after the initial injection, the mice were sacrificed, examined for tumors, and the cecal contents were analyzed to determine the moisture content and the concentrations of short-chain fatty acids (SCFA). The average number of total tumors per mouse in the MFW (2.9 +/- 0.6, P = 0.017) and WB (5.3 +/- 1.3, P = 0.373) diet groups was lower than that of the CL diet group (7.5 +/- 1.3), though there was no significant difference in tumor incidence (94.7%, 90.0% and 94.7%, respectively) between the groups. More than 90% of the tumors in each group were adenocarcinomas. The incidence of adenoma and that of carcinoma in situ in the MFW diet group (5.3% and 0%, respectively) were also lower than those in the CL diet group (26.3 and 26.3%, respectively; P = 0.180 and P = 0.046, respectively). Analysis of the cecal contents revealed a significantly higher moisture content and significantly higher concentrations of SCFA, butyrate in particular, in the MFW and WB diet groups. The results of this study indicate that the source and texture of dietary fiber can influence tumor development in CF1 mice, and more specifically that MFW is a promising and useful dietary supplement with properties serving to protect against the development of colon cancer.

Adenocarcinoma↗