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Biomedical subjects

K Ikeda

Publications and source records attributed to K Ikeda.

At least 109 records · Page 6Linked to original sources

Pyret, a Ty3/Gypsy retrotransposon in Magnaporthe grisea contains an extra domain between the nucleocapsid and protease domains.

A novel Ty3/Gypsy retrotransposon, named Pyret, was identified in the plant pathogenic fungus Magnaporthe grisea (anamorph Pyricularia oryzae). Pyret-related elements were distributed in a wide range of Pyricularia isolates from various gramineous plants. The Pyret element is 7250 bp in length with a 475 bp LTR and one conceptual ORF. The ORF contains seven nonsense mutations in the reading frame, indicating that the Pyret clone is lightly degenerate. Comparative domain analysis among retroelements revealed that Pyret exhibits an extra domain (WCCH domain) beyond the basic components of LTR retrotransposons. The WCCH domain consists of approximately 300 amino acids and is located downstream of the nucleocapsid domain. The WCCH domain is so named because it contains two repeats of a characteristic amino acid sequence, W-X(2)-C-X(4)-C-X(2)-H-X(3)-K. A WCCH motif-like sequence is found in the precoat protein of some geminiviruses, viral RNA-dependent RNA polymerase and also in an Arabidopsis protein of unknown function. Interestingly, detailed sequence analysis of the gag protein revealed that Pyret, as well as some other chromodomain-containing LTR retrotransposons, displays significant sequence homology with members of the gammaretroviruses (MLV-related retroviruses) in the capsid and nucleocapsid domains. This suggests that chromodomain-containing LTR retrotransposons and gammaretroviruses may share a common ancestor with the gag protein.

Amino Acid Motifs↗

Therapy-related myelodysplastic syndrome/acute myeloid leukemia M2 and translocation (8;21).

An 80-year-old woman developed therapy-related myelodysplastic syndrome with translocation (8;21), which was successfully treated with an acute myeloid leukemia oriented chemotherapy. Five years before admission she had received cyclophosphamide, epirubicin, and carboplatin for endometrial cancer. The leukemia cell morphology alerted us to the possibility of the presence of t(8;21) before cytogenetic results were obtained, and AML1/ETO fusion transcript was detected by reverse transcription polymerase chain reaction. She achieved complete remission after one course of idarubicin and cytosine arabinoside. She has remained in complete remission for 6 months. Our experience suggests that recognition of typical morphological features for de novo M2 acute myeloid leukemia with t(8;21) would be important in diagnosis of therapy related myelodysplastic syndrome/acute myeloid leukemia with this translocation, which could respond to an intensive chemotherapy.

Aged↗

Angiotensin II induces circadian gene expression of clock genes in cultured vascular smooth muscle cells.

BACKGROUND: Daily rhythms of mammalian physiology and endocrinology are regulated by circadian pacemakers. The master circadian pacemaker resides in the suprachiasmatic nucleus, which is located in the hypothalamus of the brain, but circadian oscillators also exist in peripheral tissues. Because many studies have demonstrated apparent circadian variations in the frequency of cardiovascular disorders, it is of great interest to investigate a possible relation between circadian gene expression and cardiovascular function. We examined whether a circadian oscillation system exists in the aorta and/or in cultured vascular smooth muscle cells (VSMCs). METHODS AND RESULTS: The mRNA levels of clock genes were assayed by northern blot analysis. The mouse aorta showed a clear circadian oscillation in the expression of mPer2, dbp, and Bmal1. Brief treatment of VSMCs with angiotensin II induced a robust increase in mPer2 gene expression, followed by a marked reduction in mPer2 mRNA levels and subsequent synchronous cycling of mPer2, dbp, and Bmal1 mRNAs. The induction of mPer2 in VSMCs by angiotensin II was completely abolished by treatment with CV11947, a specific angiotensin II type1 receptor antagonist. CONCLUSIONS: The present results demonstrate that the aorta and VSMCs possess a circadian oscillation system which is comparable to that of the suprachiasmatic nucleus and that the circadian gene expression in VSMCs is induced by angiotensin II through the angiotensin II type1 receptor. Our in vitro system will provide a useful tool to further analyze the physiological significance of the peripheral clock in cardiovascular function.

ARNTL Transcription Factors↗

Inhibition of HIV-1 infection by synthetic peptide analogues derived from the NH(2)-Terminal extracellular region of GPR1.

Several shortened peptide analogues of the N-terminal domain of GPR1, an orphan G protein-coupled receptor (GPCR), were prepared and their anti-HIV-1 activities were evaluated. Some of the prepared compounds, especially sulfated derivatives, showed potent inhibitory activity against a broad range of HIV-1, including T cell-tropic, dual cell-tropic and brain-derived (BT) cell-tropic HIV-1 strains.

Amino Acid Sequence↗

Characterization of the metal-substituted dipeptidyl peptidase III (rat liver).

Dipeptidyl peptidase III (DPP III) (EC 3.4.14.4), which has a HELLGH-E (residues 450-455, 508) motif as the zinc binding site, is classified as a zinc metallopeptidase. The zinc dissociation constants of the wild type, Leu(453)-deleted, and E508D mutant of DPP III at pH 7.4 were 4.5 (+/-0.7) x 10(-13), 5.8 (+/-0.7) x 10(-12), and 3.2 (+/-0.9) x 10(-10) M, respectively. The recoveries of the enzyme activities by the addition of various metal ions to apo-DPP III were also measured, and Co(2+), Ni(2+), and Cu(2+) ions completely recovered the enzyme activities as did Zn(2+). The dissociation constants of Co(2+), Ni(2+), and Cu(2+) ions for apo-DPP III at pH 7.4 were 8.2 (+/-0.9) x 10(-13), 2.7 (+/-0.3) x 10(-12), and 1.1 (+/-0.1) x 10(-14) M, respectively. The shape of the absorption spectrum of Co(2+)-DPP III was very similar to that of Co(2+)-carboxypeptidase A or Co(2+)-thermolysin, in which the Co(2+) is bound to two histidyl nitrogens, a water molecule, and a glutamate residue. The absorption spectrum of Cu(2+)-DPP III is also very similar to that of Cu(2+)-thermolysin. The EPR spectrum and the EPR parameters of Cu(2+)-DPP III were very similar to those of Cu(2+)-thermolysin but slightly different from those of Cu(2+)-carboxypeptidase A. The five lines of the superfine structure in the perpendicular region of the EPR spectrum in Cu(2+)-DPP III suggest that nitrogen atoms should coordinate to the cupric ion in Cu(2+)-DPP III. All of these data suggest that the donor set and the coordination geometry of the metal ions in DPP III, which has the HExxxH motif as the metal binding site, are very similar to those of the metal ions in thermolysin, which has the HExxH motif.

Animals↗

Observation of the "self-healing" of an error field island in the large helical device.

It was observed that the vacuum magnetic island produced by an external error magnetic field in the large helical device shrank in the presence of plasma. This was evidenced by the disappearance of flat regions in the electron temperature profile obtained by Thomson scattering. This island behavior depended on the magnetic configuration in which the plasmas were produced.

Journal Article↗

Tumor-specific cytotoxic T lymphocyte responses against chondrosarcoma with HLA haplotype loss restricted by the remaining HLA class I allele.

Although loss of HLA expression by malignant cells has also been demonstrated, it has not been clarified how the loss of HLA expression observed in vitro actually results in immune escape. We demonstrated two major findings: (i) a part of chromosome 6 coding for HLA haplotypes was deleted from the genome of chondrosarcoma cell line, OUMS-27; furthermore, immunohistostaining for HLA-A11 showed that the original chondrosarcoma tissue lost the expression of HLA-A11, implicating that HLA haplotype loss was already present in the original tumor tissue and (2) HLA class I-restricted and autologous tumor-specific cytotoxic T cells (CTL) were generated from peripheral blood lymphocytes of the patient with chondrosarcoma, from whom OUMS-27 originated. This CTL line was maintained by weekly stimulation with OUMS-27, and lysed OUMS-27 in an HLA-A24 dependent manner but did not either K562 or autologous (EBV)-transformed B cells. These observations indicated that OUMS-27 and its original tumor are still immunogenic and can present antigen peptides with the remaining HLA-A24, even if HLA expression is partially lost. Tumor specific immunotherapy can be applied to the treatment of malignancies, even if HLA expression is partially lost.

Aged↗

Observation of large CP violation in the neutral B meson system.

We present a measurement of the standard model CP violation parameter sin2 phi(1) based on a 29.1 fb(-1) data sample collected at the Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric-energy e(+)e(-) collider. One neutral B meson is fully reconstructed as a J/psi K(S), psi(2S)K(S), chi(c1)K(S), eta(c)K(S), J/psi K(L), or J/psi K(*0) decay and the flavor of the accompanying B meson is identified from its decay products. From the asymmetry in the distribution of the time intervals between the two B meson decay points, we determine sin2 phi(1) = 0.99+/-0.14(stat)+/-0.06(syst). We conclude that we have observed CP violation in the neutral B meson system.

Journal Article↗

Increased hydroxyl radicals in the hippocampus of stroke-prone spontaneously hypertensive rats during transient ischemia and recirculation.

It has been suggested that stroke-prone spontaneously hypertensive rats (SHRSP) show vulnerability to neuronal damage following transient ischemia. To observe the effect of hydroxyl radicals on neuronal damage in the hippocampus of SHRSP during ischemia and recirculation, we measured the levels of 2,3-dihydroxybenzoic acid (2,3-DHBA), as a biological marker of hydroxyl radicals in the hippocampus of SHRSP, by high pressure liquid chromatography-electrochemical detection. The production of hydroxyl radicals in the hippocampus during the first 20 min of recirculation was a peak in all intervals. The changes in 2,3-DHBA levels during ischemia and recirculation in SHRSP were significantly higher than in Wistar-Kyoto rats. These results suggest that neuronal damage following ischemia and recirculation is, in part, caused by the increase in hydroxyl radicals during ischemia and recirculation.

Animals↗

Cardiovascular risk factors in Tanzania: a revisit.

In this assessment of cardiovascular risk factors, we examined the prevalence of selected risk factors according to the World Health Organisation (WHO) CARDIAC Study protocol and compared them with a similar study conducted more than a decade ago. The survey was carried out in Dar es Salaam (D, urban), Handeni (H, rural) and Monduli (Mo, semi-nomadic area). Subjects aged 47-57 were recruited randomly for blood pressure and anthropometrical measurements, 24 h urine collection and blood sampling. A structured questionnaire was used to obtain dietary information. The 1998 survey studied 446 subjects, while the 1987 survey included 496 men and women. The measured weight, body mass index (BMI) and prevalence of obesity (BMI > or = 30 kg/m(2)) increased significantly among women in the 1998 survey in rural Handeni and urban Dar. The overall prevalence of obesity was higher for women in the most recent survey (22.8%, P < 0.0001). Diastolic blood pressure (DBP) was higher in the most recent survey for women in Handeni. The overall prevalence of hypertension (blood pressure > 160/95 mmHg, or antihypertensive drug use), rose to 41.1% in 1998, (P < 0.001) for men and to 38.7% (P < 0.05) for women. The mean total serum cholesterol and prevalence of hypercholesterolaemia increased significantly in the most recent survey in the three studied areas. The overall prevalence of hypercholestrolaemia (serum cholesterol > 5.2 mmol/l) was higher in the 1998 survey for both men (21.8%, P < 0.0001) and women (54.0%, P < 0.0001). The mean HDL cholesterol increased significantly in the most recent survey, with a significant reduction in the mean atherogenic index, though these were still at higher levels (men 5.8, P < 0.0001; women 5.1, P < 0.0001 vs. 1987). A strong positive correlation was observed between blood pressure (SBP and DBP) and body mass index, total serum cholesterol and sodium to potassium ratio. These data suggest that for the past decade there has been an increase in the mean levels and prevalence of selected cardiovascular risk factors in Tanzania.

Blood Pressure↗

Reduction of ion thermal diffusivity associated with the transition of the radial electric field in neutral-beam-heated plasmas in the large helical device.

Recent large helical device experiments revealed that the transition from ion root to electron root occurred for the first time in neutral-beam-heated discharges, where no nonthermal electrons exist. The measured values of the radial electric field were found to be in qualitative agreement with those estimated by neoclassical theory. A clear reduction of ion thermal diffusivity was observed after the mode transition from ion root to electron root as predicted by neoclassical theory when the neoclassical ion loss is more dominant than the anomalous ion loss.

Journal Article↗

Molecular cloning and characterization of mouse EBAG9, homolog of a human cancer associated surface antigen: expression and regulation by estrogen.

We previously identified a human estrogen-responsive gene, EBAG9 (ER-binding fragment-associated antigen9) (Watanabe, T. et al., Mol. Cell. Biol. 18, 442-449, 1998). It was later reported as RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) that induced apoptosis and suppressed the growth of several cells such as activated T cells (Nakashima, M. et al., Nat. Med. 5, 938-942, 1999). Here, we have isolated both cDNA and genomic DNA of mouse EBAG9/RCAS1. Mouse EBAG9 gene spans about 30 kb in genomic DNA and consists of 7 exons. Mouse EBAG9 cDNA encodes a protein that contains the transmenbrane segment and coiled-coil domain. An alignment between the predicted mouse and human EBAG9 shows a high degree of homology at the amino acid level (98%). Northern and Western blot analyses demonstrate that EBAG9 is expressed in several tissues including the heart, brain, spleen, liver, kidney, and testis, and also in developing embryo. In the uterus, a target organ for estrogen, the EBAG9 was shown to be upregulated in vivo by 17beta-estradiol. To determine the biological action of mouse EBAG9, NIH3T3 fibroblastic cells were incubated with recombinant EBAG9 protein, resulting in suppression of cell growth. These findings suggest that EBAG9 is an in vivo estrogen-responsive gene that inhibits the cell growth.

3T3 Cells↗

Immunohistochemical localization of neprilysin in the human cerebral cortex: inverse association with vulnerability to amyloid beta-protein (Abeta) deposition.

We investigated the immunohistochemical localization of neprilysin, a putative amyloid beta-protein (Abeta)-degrading enzyme, in postmortem human brain tissues. In the cerebral cortex, neprilysin immunoreactivity was weak, but relatively dense distribution was found in the primary somatosensory and visual cortices compared with the hippocampus and association cortices. In Alzheimer brain, neprilysin-positive dystrophic neurites occurred in senile plaques in the primary cortices, an observation that supports the relative abundance of neprilysin-positive neuronal processes. A paucity of neprilysin in the hippocampus and association cortices may contribute to the vulnerability of these areas to Abeta deposition.

Alzheimer Disease↗

Astroglial function of schizophrenic brain: a study using lobotomized brain.

The neurodevelopmental hypothesis is now being recognized as one of the most useful hypothesis for schizophrenia, and by using it, abnormalities in protein associated with neuron growth or neuronal migration have been reported. From neuron-glia interrelations in the neural development, it is important to study the function of astroglia in the schizophrenic brain. In this study, we examined the neuropathological reaction of astroglia using lobotomized brains, and a significant decrease of astroglia after artificial histological damage was observed in schizophrenic brains. We speculated that this may be due to the latent vulnerability of the dynamic function of astroglia in schizophrenia. Astroglia plays a guidance role on migration and if astroglia has latent vulnerability, we speculate that younger neurons may not sufficiently migrate during development. In further investigation of the neurodevelopmental hypothesis of schizophrenia, it will be necessary to examine the function of astroglia.

Adult↗

Diffuse neurofibrillary tangles with calcification (a form of dementia): X-ray spectrometric evidence of lead accumulation in calcified regions.

Diffuse neurofibrillary tangles with calcification (DNTC) is a form of slowly progressive dementia in which no senile plaques are observed. The calcification is one of the most characteristic features of DNTC. We examined the elemental content of certain mineral deposits (lead, magnesium, phosphorus, calcium, iron, copper and zinc) in the calcified and non-calcified regions of eight cases of DNTC, five cases of Alzheimer's disease (AD) and in eight non-demented elderly controls. The study was performed using a combination of scanning electron microscopy and X-ray spectrometry on 10% formalin-fixed brain tissue. A marked abundance of calcium and phosphorus was observed in the calcified regions of DNTC and non-DNTC brains. Although no lead was observed in the non-calcified regions of DNTC and in non-DNTC brains, traces of lead were detected exclusively in the calcified regions of DNTC brains. The implications and possible significance of the lead accumulation in DNTC brains are discussed.

Aged↗

Alternative splicing regulates the endoplasmic reticulum localization or secretion of soluble secreted endopeptidase.

A subfamily of zinc metalloproteases, represented by Neutral endopeptidase (EC ) and endothelin-converting enzyme, is involved in the metabolism of a variety of biologically active peptides. Recently, we cloned and characterized a novel member of this metalloprotease family termed soluble secreted endopeptidase (SEP), which hydrolyzes many vasoactive peptides. Here we report that alternative splicing of the mouse SEP gene generates two polypeptides, SEP(Delta) and SEP. After synthesis, both isoforms are inserted into the endoplasmic reticulum (ER) as type II membrane proteins. SEP(Delta) then becomes an ER resident, whereas SEP, which differs by only the presence of 23 residues at the beginning of its luminal domain, is proteolytically cleaved by membrane secretase(s) in the ER and transported into the extracellular compartment. An analysis of the chimeric proteins between SEP(Delta) and bovine endothelin-converting enzyme-1b (bECE-1b) demonstrated that the retention of SEP(Delta) in the ER is mediated by the luminal domain. In addition, the dissection of the chimeric bECE-1b/SEP insertion showed that its insertion domain is obviously responsible for its secretion. A series of mutagenesis in this region revealed that the minimal requirement for cleavage was found to be a WDERTVV motif. Our results suggest that the unique subcellular localization and secretion of SEP proteins provide a novel model of protein trafficking within the secretory pathway.

Alternative Splicing↗

Expression of connexin 30 in the developing mouse cochlea.

Mutations in the GJB6 gene encoding connexin 30 (Cx30) can cause dominant forms of nonsyndromic deafness. By studying immunohistochemical localization of Cx30 in the mouse cochlea at different ages from 0 to 30 days after birth, we found that the expression of Cx30 is nearly the same as that of Cx26. These findings suggest that as well as Cx26, Cx30 may also contribute to the generation and maturation of endocochlear potential.

Age Factors↗