Search PubMed⌕ Search

Biomedical subjects

T Imura

Publications and source records attributed to T Imura.

At least 19 recordsLinked to original sources
PubMed2004

Coacervate formation from natural glycolipid: one acetyl group on the headgroup triggers coacervate-to-vesicle transition.

Coacervate (L3 phase) formation of the single component "natural" glycoliped biosurfactant, MEL-A, was observed for the first time by using an optical microscope, a confocal laser scanning microscope (CLSM), and a freeze-fracture electron microscope (FF-TEM). It was also found that only a slight decrease in spontaneous curvature resulting from the absence of one acetyl group on the headgroup induced a drastic morphological change in the 3D self-assembled structure from coacervates (L3 phase) to ordered vesicles (Lalpha phase).

Colloids↗
PubMed2001

Oxidative stress causes abnormal accumulation of familial amyotrophic lateral sclerosis-related mutant SOD1 in transgenic Caenorhabditis elegans.

Mutations in the Cu/Zn superoxide dismutase (SOD1) genes are present in approximately 20% of families suffering from familial amyotrophic lateral sclerosis (FALS). Results from several transgenic studies in which FALS-related SOD1 mutations have been expressed have suggested that mutant SOD1 proteins induce cytotoxicity through a toxic gain of function, although the specific mechanism of this has not been fully clarified. To investigate the mechanism of toxicity induced by the mutant SOD1 associated with FALS, we generated transgenic Caenorhabditis elegans strains that contain wild-type and mutant human A4V, G37R and G93A SOD1 recombinant plasmids. The transgenic strains expressing mutant human SOD1 showed greater vulnerability to oxidative stress induced by 0.2 mM paraquat than a control that contained the wild-type human SOD1. In the absence of oxidative stress, mutant human SOD1 proteins were degraded more rapidly than the wild-type human SOD1 protein in C.elegans. In the presence of oxidative stress, however, this rapid degradation was inhibited, and the transgenic C.elegans co-expressing mutant human SOD1 and green fluorescent proteins (GFPs) in muscle tissues demonstrated discrete aggregates in the adult stage. These results suggest that oxidative damage inhibits the degradation of FALS-related mutant human SOD1 proteins, resulting in an aberrant accumulation of mutant proteins that might contribute to the cytotoxicity.

Amyotrophic Lateral Sclerosis↗
PubMed2001

Effect of adsorption of bovine serum albumin on liposomal membrane characteristics.

The effect of adsorption of bovine serum albumin (BSA) on the membrane characteristics of liposomes at pH 7.4 was examined in terms of zeta potential, micropolarity, microfluidity and permeability of liposomal bilayer membranes, where negatively charged L-alpha-dipalmitoylphosphatidylglycerol (DPPG)/L-alpha-dipalmitoylphosphatidylcholine (DPPC), negatively charged dicetylphosphate (DCP)/DPPC and positively charged stearylamine (SA)/DPPC mixed liposomes were used. BSA with negative charges adsorbed on negatively charged DPPG/DPPC mixed liposomes but did not adsorb on negatively charged DCP/DPPC and positively charged SA/DPPC mixed liposomes. Furthermore, the adsorption amount of BSA on the mixed DPPG/DPPC liposomes increased with increasing the mole fraction of DPPG in spite of a possible electrostatic repulsion between BSA and DPPG. Thus, the adsorption of BSA on liposomes was likely to be related to the hydrophobic interaction between BSA and liposomes. The microfluidity of liposomal bilayer membranes near the bilayer center decreased by the adsorption of BSA, while the permeability of liposomal bilayer membranes increased by the adsorption of BSA on liposomes. These results are considered to be due to that the adsorption of BSA brings about a phase separation in liposomes and that a temporary gap is consequently formed in the liposomal bilayer membranes, thereby the permeability of liposomal bilayer membranes increases by the adsorption of BSA.

Journal Article↗
PubMed2001

Effects of lysozyme and bovine serum albumin on membrane characteristics of dipalmitoylphosphatidylglycerol liposomes.

The effects of adsorption of two kinds of proteins on the membrane characteristics of liposomes were examined at pH 7.4 in terms of adsorption amounts of proteins on liposomes, penetrations of proteins into liposomal bilayer membranes, phase transition temperature, microviscosity and permeability of liposomal bilayer membranes, using positively charged lysozyme (LSZ) and negatively charged bovine serum albumin (BSA) as proteins and negatively charged L-alpha-dipalmitoylphosphatidylglycerol (DPPG) liposomes. The saturated adsorption amount of LSZ was 720 g per mol of liposomal DPPG, while that of BSA was 44 g per mol of liposomal DPPG. The penetration of LSZ into DPPG lipid membranes was greater than that of BSA. The microviscosity in the hydrophobic region of liposomal bilayer membranes increased due to adsorption (penetration) of LSZ or BSA, while the permeability of liposomal bilayer membranes increased. The gel-liquid crystalline phase transition temperature of liposomal bilayer membranes was not affected by adsorption of LSZ or BSA, while the DSC peak area (heat of phase transition) decreased with increasing adsorption amount of LSZ or BSA. It is suggested that boundary DPPG makes no contribution to the phase transition and that boundary DPPG and bulk DPPG are in the phase-separated state, thereby increasing the permeability of liposomal bilayer membranes through adsorption of LSZ or BSA. A possible schematic model for the adsorption of LSZ or BSA on DPPG liposomes was proposed.

Journal Article↗
PubMed2001

Preparation of liposomes containing Ceramide 3 and their membrane characteristics.

Liposomes composed of Ceramide 3, [2S,3S,4R-2-stearoylamide-1,3,4-octadecanetriol], and L-alpha-dipalmitoylphosphatidylcholine (DPPC) were prepared by varying the amount of Ceramide 3, and the effects of Ceramide 3 on the liposome formation, particle size, dispersibility, microviscosity and phase transition temperature were examined by means of a microscopy, a dynamic light scattering method, a fluorescence polarization method, a differential scanning calorimetry (DSC) and so on. All the DPPC was able to contribute to the formation of liposomes up to 0.130 mol fraction of Ceramide 3. The particle size of liposomes was almost unaffected by the addition of Ceramide 3. The dispersibility of liposomes containing Ceramide 3 was maintained for at least 15 days. The microviscosity of liposomal bilayer membranes in the liquid crystalline state was increased with increasing the mole fraction of Ceramide 3, while that in the gel state was independent of the mole fraction of Ceramide 3. The phase transition temperature from gel to liquid crystalline states of DPPC bilayer membranes was shifted upwards with the addition of Ceramide 3, indicating a cooperative interaction between DPPC and Ceramide 3 molecules. However, a sharp DSC peak became broad and split at higher mole fractions of Ceramide 3, suggesting a phase separation in the mixed DPPC/Ceramide 3 liposomal bilayer membranes. These phenomena were suggested to be related to the previously observed fact for the mixed DPPC/Ceramide 3 monolayers that Ceramide 3 interacts with DPPC in the liquid-expanded phase with consequent phase separation accompanied with domain formation.

Journal Article↗
PubMed2001

Spontaneous arterial baroreflex control of the heart rate during head-down tilt in heat-stressed humans.

The purpose of this study was to elucidate the effect of raised body temperature per se during acute heat stress on the spontaneous arterial baroreflex control of heart rate (fc) in humans. To investigate whether unloading of cardiopulmonary baroreceptors during whole-body heating would alter the arterial baroreflex control of fc, we controlled loading of the cardiopulmonary baroreceptors by head-down tilt (HDT) at angles of 5 degrees, 10 degrees, 15 degrees, and 30 degrees during heat stress produced by hot-water-perfused suits. The sensitivity of the arterial baroreceptor-cardiac reflex was calculated from the spontaneous changes in beat-to-beat arterial pressure and fc. As an index of cardiopulmonary baroreceptor loading, the left atrial diameter (LAD) was measured by echocardiography. During whole-body heating, the LAD decreased with the rising body core temperature and increased with the HDT. The decreased LAD during heating almost recovered to the normothermic control level by 10 degrees HDT. In the supine position, cardiac baroreflex sensitivity remained unchanged during heating. Arterial pressure, fc and cardiac baroreflex sensitivity were not changed by HDT ranging from 5 degrees to 30 degrees during heating. These results suggest that cardiac baroreflex sensitivity remain unchanged during graded loading of the cardiopulmonary baroreceptors in heat-stressed humans. Also, we conclude that the sensitivity of the spontaneous arterial baroreflex controlling the fc is not influenced by raised body temperature per se during acute heat stress.

Adult↗
PubMed2000

Distribution of the 4F2 light chain, LAT1, in the mouse brain.

LAT1 (the 4F2-light chain 1) is a component of the CD98 surface antigen which participates in multiple functions including amino acid transport, cell survival, cell fusion and integrin activation. We examined the distribution of LAT1 in the mouse brain using immunohistochemistry. LAT1 was expressed on the microvessels, the subfornical organ, the subcommissural organ, ventromedial nucleus of the hypothalamus, subgranular zone of the dentate gyrus, ependymal layer of the lateral ventricles, and the olfactory bulb. LAT1-positive cells incorporated bromodeoxyuridine in the latter three regions where neurogenesis occurs in adult mouse brain, indicating that LAT1 is involved in neuronal cell proliferation, as well as in amino acid transport in these regions.

Amino Acid Transport Systems↗
PubMed2000

Opposing effects of adenosine on the survival of glial cells exposed to chemical ischemia.

Extracellular adenosine (Ado) accumulates during brain ischemia. To investigate the pathophysiological role of Ado on glial cells under ischemic conditions, we examined the effect of Ado on the survival of C6 glial cells exposed to chemical ischemia (CI). Treatment with Ado during exposure to CI showed a marked protective effect, that was mediated via intracellular transport and conversion of Ado to inosine (Ino). In contrast, Ado exacerbated CI-mediated cell death when it was added during the recovery time after exposure to CI. Ado cytotoxicity was largely mediated via intracellular transport, but conversion of Ado to Ino abolished its toxicity. Ado-induced cell death was characteristic of apoptosis, and Ado increased the expression of a pro-apoptotic product Bax but decreased that of an anti-apoptotic product Bcl-2. Ado also suppressed the induction of two stress proteins HSC70 and HSP27. Furthermore, Ado induced cytochrome c release and increased caspase-3-like activity. These results indicate the dual opposing effects of Ado on glial cell survival. Intracellular accumulation of Ado can be both cytoprotective and cytotoxic, depending on its metabolic pathway.

Adenosine↗
PubMed1999

Differential expression of small heat shock proteins in reactive astrocytes after focal ischemia: possible role of beta-adrenergic receptor.

Small heat shock proteins (sHSPs), a family of HSPs, are known to accumulate in the CNS, mainly in astrocytes, in several pathological conditions such as Alexander's disease, Alzheimer's disease, and Creutzfeldt-Jakob disease. sHSPs may act not only as molecular chaperones, protecting against various stress stimuli, but may also play a physiological role in regulating cell differentiation and proliferation. In the present study, we have demonstrated that transient focal ischemia in rats dramatically induced HSP27 but not alpha B-crystallin (alphaBC), both of which are members of sHSPs, in reactive astrocytes. In contrast, in vitro chemical ischemic stress induced both HSP27 and alphaBC in cultured glial cells to the same extent. Dibutyryl cAMP (dBcAMP) and isoproterenol, a beta-adrenergic receptor (betaAR) agonist, enhanced HSP27 expression but suppressed alphaBC, and changed the shape of the cells to a stellate form. dBcAMP and isoproterenol inhibited cell proliferation under normal conditions. An increase in betaAR-like immunoreactivity was also observed in reactive astrocytes in vivo. These results, together with recent findings that betaAR plays an important role in glial scar formation in vivo, raise the possibility that betaAR activation modulates sHSP expression after focal ischemia and is involved in the transformation of astrocytes to their reactive form.

Animals↗
PubMed1999

Selective induction of glial glutamate transporter GLT-1 by hypertonic stress in C6 glioma cells.

Glial glutamate transporter GLT-1 mRNA was selectively induced in C6 glioma cells exposed to hypertonic stress (HS), while the expression of two other subtypes, GLAST and EAAC1, was suppressed. HS increased phosphorylation of the MAPK family, ERK, p38 MAPK, and JNK. Treatment with a PKC inhibitor showed that phosphorylation of both p38 MAPK and JNK is PKC-dependent but ERK phosphorylation is independent. Inhibition of either ERK or p38 MAPK did not abolish GLT-1 mRNA induction. Inhibition of PKC also had no effect. These findings indicate that the induction of GLT-1 mRNA by HS is independent of the MAPK pathways. This is the first report that the expression of glial glutamate transporters is osmotically regulated.

ATP-Binding Cassette Transporters↗
PubMed1999

A common mutation of cholesteryl ester transfer protein gene in dialysis patients.

BACKGROUND: In patients on maintenance hemodialysis, a decreased concentration of high-density lipoprotein cholesterol (HDL-C) is an apparent independent risk factor for vascular disease (VD). A common missense mutation of cholesteryl ester transfer protein (CETP) gene, D442G (Asp442 to Gly), increases HDL-C levels, but the mutation may also diminish the activity of reverse cholesterol transport. METHODS: We compared the genotype distribution of the D442G polymorphism and postprandial serum lipid levels between patients with and without VD in 414 hemodialysis patients. RESULTS: Serum levels of total cholesterol and HDL-C did not differ in patients with the mutation [group M (+)] and without the mutation [group M (-)] and in patients with and without VD. However, patients with below median HDL-C levels (< 45 mg/dl) had a significantly higher prevalence of VD than those with above median HDL levels (26.0 vs. 15.2%, P < 0.01). Moreover, in this low-HDL-C subgroup, group M (+) patients had a significantly higher prevalence of VD than group M (-) patients (54.5 vs. 24.4%, P < 0.05). In the subgroup, group M (+) patients with VD had higher levels of total cholesterol and a higher atherogenic index than those without VD, whereas group M (-) patients with VD had lower levels of total cholesterol and a lower atherogenic index than those without VD. CONCLUSIONS: The D442G mutation may be a risk factor for atherosclerotic complications in dialysis patients with HDL-C levels below 45 mg/dl. Atherogenic lipid profiles may promote atherosclerosis in the patients with the mutation, but not in those with no mutation.

Adult↗
PubMed1999

Apolipoprotein E phenotypes in hemodialysis patients.

BACKGROUND: Apolipoprotein (apo) E polymorphism consists of three major isoproteins (E2, E3, and E4). Because of their difference in a lipid-modulating effect, the polymorphism has been reported to affect the morbidity of atherosclerosis in general population. Therefore, in hemodialysis (HD) patients, the apo E polymorphism may also modulate serum levels of cholesterol and susceptibility to atherosclerotic vascular disease. METHODS: We determined apo E phenotypes in 493 HD patients and 422 controls. We also investigated vascular risk profile and measured postprandial serum levels of lipids and apos in the dialysis patients. RESULTS: We found a similar phenotype distribution and allele frequency between HD patients and healthy controls. Serum levels of total cholesterol, triglyceride, and apo A I, A II, and C III did not differ significantly among patients with phenotypes apo E2/3, E3/3, and E3/4. Patients with apo E3/4 had significantly lower levels of high-density lipoprotein cholesterol, significantly higher levels of low-density lipoprotein cholesterol (LDL-C), and a higher atherogenic index than those with apo E2/3 (LDL-C, 100 +/- 30 vs. 82 +/- 35 mg/dl, P < 0.01; the index, 3.3 +/- 1.7 vs. 2.3 +/- 1.3, P < 0.01). Patients with apo E3/4 showed a tendency toward higher levels of apo B than patients with apo E2/3 or apo E3/3. Multiple logistic regression analysis revealed that age and diabetes mellitus, but not apo E phenotypes, were independent risk factors for vascular disease. CONCLUSIONS: Apo E polymorphism modulates cholesterol metabolism in dialysis patients but appears to have little association with the prevalence of atherosclerotic complications in the patients.

Age Factors↗
PubMed1999

A cholesteryl ester transfer protein gene mutation and vascular disease in dialysis patients.

Among patients undergoing maintenance hemodialysis, a decreased high-density lipoprotein cholesterol (HDL-C) concentration is among the most common abnormalities of lipid metabolism and apparently is an independent risk factor for vascular disease. A common missense mutation of cholesteryl ester transfer protein gene, D442G (Asp 442 to Gly), increases HDL-C levels through the reduced activity of cholesteryl ester transfer from HDL to VLDL, but the mutation also may lead to reduced activity of reverse cholesterol transport. To investigate the effect of the D442G polymorphism on atherosclerotic complications in dialysis patients, the genotype and allele frequency of the polymorphism were determined in 414 unselected dialysis patients and 220 control subjects, and postprandial serum lipid levels were measured in the dialysis patients. A similar genotype distribution was found between hemodialysis patients and healthy control subjects, and in dialysis patients with and without vascular disease. Serum levels of total cholesterol and HDL-C did not differ between patients with and without the mutation and in patients with and without vascular disease. However, patients with sub-median HDL-C levels (<45 mg/dl) had an independent odds ratio of 1.8 for vascular disease (95% confidence interval, 1.04 to 3.2; P < 0.05). In this low-HDL-C subgroup, patients with the D442G mutation had a significantly higher prevalence of vascular disease than those with no mutation (54.5% versus 24.4%; P < 0.05), and an independent odds ratio of 4.9 (95% confidence interval, 1.05 to 22.65; P < 0.05). In conclusion, the D442G mutation is an independent risk factor for atherosclerotic complications in dialysis patients with HDL-C levels below 45 mg/dl.

Adolescent↗
PubMed1998

Mutation in the pleckstrin homology domain of the human phospholipase C-delta 1 gene is associated with loss of function.

The delta-type phospholipase C (PLC) is thought to be evolutionally the most basal form in the mammalian PLC family. One of the delta-type isoforms, PLC-delta 1, binds to both phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) with a high affinity via its pleckstrin homology (PH) domain. We report here a missense mutation in the region encoding the C-terminal PH domain of the human PLC-delta 1. This is also the first report of a mutation in the human PLC genes. A single base substitution (G to A) causes the amino acid replacement, Arg105 to His. Site-directed mutagenesis of the glutathione-S-transferase (GST)/PLC-delta 1 fusion protein changing Arg105 to His resulted in a fourfold decrease in the affinity of specific Ins(1,4,5)P3 binding and a reduction in PtdIns(4,5)P2 hydrolysing activity to about 40% of that of the wild-type enzyme. This remarkable loss of function can be interpreted in terms of a conformational change in the PH domain.

Blood Proteins↗
PubMed1998

[Detection of apolipoproteins E5 and E7 by a widely used commercial ApoE IFE kit--evidence provided by genotyping].

The purpose of this study is to examine a possibility to detect apolipoprotein (apo) E5 and E7 isoproteins with a commercial kit widely used (Phenotyping Apo E IFE System, Jokoh Co. LTD., Tokyo) and to clarify the frequency of the rare alleles in Central Japan. A total of 1,445 subjects living in Central Japan (1,030 hemodialysis patients and 415 apparently healthy individuals) was phenotyped for apo E isoproteins with the kit using isoelectric focusing with immunoblotting. In 23 subjects, unique apo E4 isoproteins, which migrate more basically than apo E4 isoprotein, were found. These unique isoproteins were proved to be apo E5 or E7 isoproteins by PCR with restriction fragment length polymorphism and with amplification refractory mutation systems, respectively. No significant differences in the frequencies of apo E5 or apo E7 alleles were observed between healthy individuals and hemodialysis patients (0.011 vs. 0.018, NS). The frequencies of apo E5 and E7 alleles were 0.001 and 0.005, respectively, in healthy individuals, and 0.003 and 0.005, respectively, in hemodialysis patients. These data in Central Japan were consistent with those in Western Japan (Matsunaga, et al, Clin Genet, 1995). These results indicate that the commercial kit is applicable to detect the rare alleles, apo E5 and E7 alleles and that the frequencies of the rare alleles in Central Japan are similar to those in Western Japan.

Adult↗
PubMed1996

Renal functional measurements in young rats with chronic inhibition of nitric oxide synthase.

The purpose of the present study was to examine renal functional changes caused by chronic blockade of nitric oxide (NO) synthesis in young rats. Two types of NO synthase inhibitor were used: NG-nitro-L-arginine methyl ester (L-NAME) as a non-selective inhibitor and aminoguanidine (AG) as a selective inhibitor of the inducible isoform. Oral administration of L-NAME (20-80 mg/dL of drinking water), not AG (400 mg/dL), for 4 weeks induced systemic hypertension in the treated rats. Both inhibitors caused a significant reduction in urinary excretion of NO2-/NO3-. Rats treated with L-NAME developed proteinuria and tubular enzymuria (high excretion of N-acetyl-beta-D-glucosaminidase) in a dose-dependent fashion, with normal serum levels of creatinine, albumin and cholesterol. Chronic AG administration did not alter the urinary levels of protein and N-acetyl-beta-D-glucosaminidase or serum laboratory values. Overall, these observations highlight the importance of the continuous generation of NO by the constitutive isoform in the control of vascular tone and the maintenance of renal glomerular and tubular function. Oral administration of L-NAME may serve as a model of chronic NO-deficient hypertension with renal injury in young rats.

Animals↗