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Biomedical subjects

M Ikeda

Publications and source records attributed to M Ikeda.

At least 163 records · Page 9Linked to original sources
PubMed2001

Interaction between monocytes and vascular endothelial cells induces adrenomedullin production.

Adrenomedullin (AM), a potent vasodilator peptide, has natriuretic effects, and its plasma concentration is elevated in cardiovascular diseases. In the present study, we investigated the induction of AM expression due to interactions between THP-1 cells (human monocytic cell line) and human umbilical cord vein endothelial cells (HUVECs). AM levels in the culture medium were measured by radioimmunoassay. The luciferase vector containing the 5'-flanking region of the human AM gene was transfected into either HUVECs or THP-1 cells. Addition of THP-1 cells to HUVECs for 48 h induced marked increases in AM levels, which were 16-fold higher than those of HUVECs alone. Luciferase vectors containing the 5'-flanking region of human AM gene (pLCF-1534) were transferred into THP-1 cells or HUVECs. Addition of THP-1 cells to pLCF-1534-transfected HUVECs induced an increase in luciferase activity in cell lysates, which was 5-fold higher than that of the transfected HUVECs alone. In contrast, the luciferase activity of lysates from pLCF-1534-transfected THP-1 cells was not affected by coculture with HUVECs. A separate coculture experiment revealed that direct contact of THP-1 cells and HUVECs contributed to enhanced AM production in the cocoulture. Co-incubation of the cell membrane fraction from THP-1 cells augmented AM production by HUVECs. Both anti-interleukin (IL)-1alpha antibody and IL-1 receptor antagonist significantly inhibited AM production in the cocultures. The cell-to-cell interaction between monocytes and HUVECs induces AM production by HUVECs, which may play an important role in the pathogenesis of vascular disorders.

Adrenomedullin↗
PubMed2001

Trehalose suppresses lipopolysaccharide-induced osteoclastogenesis bone marrow in mice.

We have previously shown that trehalose suppresses bone loss in ovariectomized (OVX) mice by way of inhibiting osteoclast differentiation in bone marrow. Also, trehalose inhibits the secretion of interleukin-6 in bone marrow cell cultures, resulting in a decrease in osteoclast formation. In this study, we examined the effect of trehalose on osteoclastogenesis using another model of bone resorption, namely lipopolysaccharide (LPS)-stimulated osteoclast induction. Mice were given trehalose (1g/kg) by gastric intubation for 5 consecutive days, and 24 hours later, 14 mg/kg of LPS was injected intraperitoneally. Trehalose significantly suppressed LPS-induced tumor necrosis factor (TNF)-alpha production after 90 min and decreased the number of osteoclasts in the bone marrow 48 hours after LPS injection. These results indicate that trehalose suppresses excessive osteoclastogenesis not only in OVX mice but also in a LPS-induced bone resorption mouse model and further suggest that the latter finding may be mediated at least in part through a decrease in TNF-alpha production.

Journal Article↗
PubMed2001

Identification of two novel mutations in the CLCN5 gene in Japanese patients with familial idiopathic low molecular weight proteinuria (Japanese Dent's disease).

Two Japanese patients, belonging to unrelated families, with idiopathic low-molecular-weight proteinuria (LMWP; Japanese Dent's disease) showed novel mutations of the gene encoding renal-specific chloride channel 5 (CLC-5). Proteinuria was first noticed at the ages of 2 and 3 years in patients 1 and 2, respectively. During follow-up, marked increases in urinary ss(2)-microglobulin levels, hypercalciuria, and high levels of urinary excretion of growth hormone were observed in both patients. Nephrocalcinosis was detected in patient 2. Renal biopsy specimens from both patients showed minimal alterations in glomeruli and tubulointerstitium, except for mild mesangial proliferation in patient 2. DNA sequence analysis of the entire 2,238-bp coding region and exon-intron boundaries of the CLCN5 gene showed the presence of two novel mutations in exon 10, consisting of one missense mutation (I524K) in patient 1 and one nonsense mutation (R637X) in patient 2. DNA analysis and measurement of urinary ss(2)-microglobulin levels in family members indicated an X-linked mode of inheritance in patient 1 and sporadic occurrence in patient 2. These results have expanded our understanding of the association between idiopathic LMWP (Japanese Dent's disease) and mutations of the CLCN5 gene.

Adolescent↗
PubMed2001

Reversible posterior leukoencephalopathy in a patient with minimal-change nephrotic syndrome.

A 9-year-old boy with nephrotic syndrome was transferred to our hospital because of acute renal failure and disturbance of consciousness after high-dose methylprednisolone therapy. He developed severe headache, visual disturbance, and generalized seizures. Brain computed tomography (CT) scan revealed multiple, bilateral, low-density areas in the parieto-occipital lobes. Magnetic resonance imaging (MRI) disclosed a high signal intensity area on T2-weighted images and a low signal intensity area on T1-weighted images in the same lesion. Follow-up brain CT scan and MRI, 2 weeks after the first studies, showed complete resolution of the abnormal lesions, which suggested the diagnosis of reversible posterior leukoencephalopathy syndrome (RPLS). Hypertension and high-dose methylprednisolone administration to the patient in the nephrotic state may be causes of this uncommon syndrome in this case. This is the first report of RPLS in nephrotic syndrome with hypertension not associated with cyclosporine administration.

Brain Diseases↗
PubMed2001

The sulphydryl reagent, N-ethylmaleimide, disrupts sleep and blocks A1 adenosine receptor-mediated inhibition of intracellular calcium signaling in the in vitro ventromedial preoptic nucleus.

To explore the neuronal signaling mechanisms underlying sleep regulation in the rat, the present study examined continuous intra-third ventricle infusion of N-ethylmaleimide (NEM), a sulphydryl reagent that inhibits G(i/o) protein-coupled receptor-mediated signaling pathways. The diurnal infusion of NEM (0.01-10 micromol/10 h) dose-dependently inhibited both non-rapid eye movement sleep and rapid eye movement sleep. A maximal dose of NEM (10 micromol/10 h) dramatically inhibited day-time sleep (-57% for non-rapid eye movement sleep and -89% for rapid eye movement sleep) with a compensatory increase of sleep during the subsequent night-time (+33% for non-rapid eye movement sleep and +259% for rapid eye movement sleep). The day-time brain temperature was also increased by NEM, demonstrating effects of NEM on both sleep and body temperature levels. Immunostaining of the rat hypothalamus with a monoclonal antibody against the A1 adenosine receptor (A1R) was used to explore the distribution of a sleep-related G(i/o) protein-coupled receptor. Robust A1R-like immunoreactivity was found in the ventromedial preoptic nucleus and the supraoptic nucleus. Fura-2-based Ca(2+) imaging analysis of acute hypothalamic slices further demonstrated that the A1R agonist N(6)-cyclopentyladenosine (CPA; 200 nM) inhibited spontaneous Ca(2+) oscillations and high potassium (80 mM)-induced Ca(2+) flux in the ventromedial preoptic nucleus, while NEM (100-300 microM) and an A1R antagonist 8-cyclopentyl-dipropylxanthine (300 nM) blocked the CPA actions and increased the high potassium-induced Ca(2+) flux. From these results we suggest that NEM-sensitive G protein-coupled receptor(s) may play an important role in the regulation of sleep and body temperature in the rat and one possible mechanism is an A1R-mediated regulation of intracellular Ca(2+) concentrations in the ventromedial preoptic nucleus.

Adenosine↗
PubMed2001

Preventive effect of Coriandrum sativum (Chinese parsley) on localized lead deposition in ICR mice.

The preventive effect of Coriandrum sativum, Fam. UMBELLIFERAE (Chinese parsley) on lead deposition was investigated in male ICR mice given lead (1000 ppm) as lead acetate trihydrate in drinking water for 32 days. Administration of Chinese parsley to mice by gastric intubation was performed for 25 days from day 7 after the start of lead exposure up to the end of the experiment. The mice were then sacrificed for comparison of lead distribution. The lead reached its highest concentration in the femur but localized lead deposition in the femur was significantly decreased by meso-2,3-dimercaptosuccinic acid (DMSA), a chelating agent used as a positive control to validate this experimental model. Administration of Chinese parsley also significantly decreased lead deposition in the femur and severe lead-induced injury in the kidneys. In addition, urinary excretion of delta-aminolevulinic acid (ALA) which is known to increase with lead intake was significantly decreased after administration of Chinese parsley. The MeOH extract of Chinese parsley also reduced lead-induced inhibition of delta-aminolevulinic acid dehydratase (ALAD) activity in vitro. These results suggest that Chinese parsley has suppressive activity on lead deposition, probably resulting from the chelation of lead by some substances contained in Chinese parsley.

Animals↗
PubMed2001

Molecular design of artificial molecular and ion recognition systems with allosteric guest responses.

Positive or negative allosterisms are ubiquitously seen in nature where the biological events must be efficiently regulated in response to chemical or physical signals from the outside world. The biomimetic design of such allosteric systems is of great significance in order to regulate the complexation ability or the catalytic activity of artificial receptors according to an allosteric manner. Furthermore, the methodology is very useful to amplify and convert weak chemical or physical signals into other signals which are convenient for us to read out and record. Allosteric systems are classified into four different categories: positive heterotropic, negative heterotropic, positive homotropic, and negative homotropic. In this Account, we account for our artificial allosteric systems and discuss the basic concept for molecular design of such allosteric systems and what kinds of new functions come out of such dynamic systems.

Allosteric Site↗
PubMed2001

Positive allosteric systems designed on dynamic supramolecular scaffolds: toward switching and amplification of guest affinity and selectivity.

Positive homotropic allosterism appears in important information transduction processes where chemical and physical signals are efficiently amplified. The phenomena are ubiquitous in nature, but the general methodology for the design of such allosteric systems is not yet established in an artificial system. This account reviews such artificial receptors that can bind guest ions and molecules in a positive allosteric manner and discusses what kinds of factors are indispensable as scaffolds in the design of this novel class of allosteric systems and what common factors are needed to realize the cooperativity. It has been shown that the scaffolds are mostly dynamic and are skillfully combined with the molecular recognition systems so that the subsequent guest binding can occur more favorably than the first guest binding. In addition, it has been suggested that positive homotropic allosterism can be utilized as a new strategy to attain high guest selectivity and guest affinity which cannot be attained by conventional 1:1-type guest binding.

Allosteric Site↗
PubMed2001

Activities of enzymes in the malate-aspartate shuttle in the peripheral leukocytes of dogs and cats.

The activities of the enzymes involved in the malate-aspartate shuttle and the expression of malate dehydrogenase (MDH), a rate-limiting enzyme in the NADH shuttle that produces ATP in glucose metabolism in leukocytes, were determined to investigate the differences in this shuttle system in the peripheral leukocytes of dogs and cats. There were no significant differences between dogs and cats in plasma glucose, immunoreactive insulin, free fatty acid or triglyceride concentrations. The activities of cytosolic and mitochondrial MDH and of mitochondrial glutamate dehydrogenase (GLDH) in canine leukocytes were significantly higher than in feline leukocytes. High activities of MDH in canine leukocytes were confirmed by RT-PCR analysis on the total RNA extracted from leukocytes. It was concluded that there were significant differences between dogs and cats in the NADH shuttle system.

Animals↗
PubMed2001

Evaluation of oral health promotion in the workplace: the effects on dental care costs and frequency of dental visits.

UNLABELLED: An oral health promotion program has been conducted since 1989 at a shipyard in Japan. AIMS: The purpose of the present study was to assess the impact of oral health promotion in the workplace in terms of dental care costs and frequency of dental visits. METHODS: This program consisted of orientation, an initial regimen, and group counseling. The initial regimen included an evaluation of each participant's oral health status, and instruction concerning oral hygiene, and prevention of oral disease. The participants were selected with each unit being a preexisting peer group. Eighty-seven participants were compared with 216 control subjects in terms of annual dental care costs and frequency of dental visits in four periods: the 1-year period before the program, the 1st year after the program, the 2nd year after, and the 3rd year after. RESULTS: The annual mean dental care cost in the participant group for the year prior to the program was higher than that in the control group (21,317 vs. 17,116 yen). In the 1st year after the program, the difference increased (26,642 vs. 19,481 yen). In the 2nd and 3rd years after the program, dental care costs in the participant group were lower than those in the control group (2nd year: 18,305 vs. 22,841 yen, 3rd year: 16,911 vs. 21,920 yen). CONCLUSIONS: It can be concluded that this oral health promotion program in the workplace contributed to saving of costs associated with dental care. The workplace can be regarded as a key area for implementation of an oral health care system to make good use of limited resources.

Dental Care↗
PubMed2001

Effects of potassium channel and Na+-Ca2+ exchange blockers on the responses of slowly adapting pulmonary stretch receptors to hyperinflation in flecainide-treated rats.

1. The effects of K(+) channel blockers, such as 4-aminopyridine (4-AP) and tetraethylammonium (TEA), and a reverse-mode Na(+)-Ca(2+) exchange blocker, 2-[2-[4-(4-nitrobenzyloxyl) phenyl] ethyl] isothiourea methanesulphonate (KB-R7943), on the responses of slowly adapting pulmonary stretch receptor activity to hyperinflation (inflation volume=3 tidal volumes) were investigated in anaesthetized, artificially ventilated, unilaterally vagotomized rats after pretreatment with a Na(+) channel blocker flecainide. The administration of flecainide (9 mg kg(-1)) at a dose greater than that which abolished 50 microg kg(-1) veratridine-induced SAR stimulation also inhibited hyperinflation-induced stimulation of SARs. 2. In flecainide-treated animals, administration of 4-AP (0.7 and 2 mg kg(-1)) stimulated SAR activity during normal inflation and also caused a partial blockade of hyperinflation-induced SAR inhibition. 3. The discharges of SARs during normal inflation in flecainide-treated animals were not significantly altered by administration of either TEA (2 and 7 mg kg(-1)) or KB-R7943 (1 and 3 mg kg(-1)), but both K(+) channel and Na(+)-Ca(2+) exchange blockers partially attenuated hyperinflation-induced SAR inhibition. 4. These results suggest that hyperinflation-induced SAR inhibition in the presence of flecainide (9 mg kg(-1)) involves the activation of several K(+) conductance pathways.

Animals↗
PubMed2001

Relative validity of a semi-quantitative food frequency questionnaire versus 28 day weighed diet records in Japanese female dietitians.

OBJECTIVE: To assess the relative validity of a semi-quantitative food frequency questionnaire (SQFFQ) against 28 day weighed diet records (WDRs). SUBJECTS AND METHODS: The SQFFQ was administered to 106 (21 male and 85 female) Japanese dietitians in Aichi Prefecture in autumn, 1996 and four-season consecutive 7 day WDRs were carried out during 1996-1997. We evaluated validity of intakes of 15 foods and 31 macro- and micro-nutrients based on the SQFFQ against those according to 28 day WDRs among 79 Japanese female dietitians. RESULTS: Mean daily intakes of selected foods and nutrients determined by the SQFFQ were generally equivalent to those measured by 28 day WDRs. Pearson's de-attenuated correlation coefficients (CCs) with log-transformation and energy-adjustment between intakes of selected foods and nutrients quantified by the SQFFQ and 28 day WDRs (minimum-median-maximum) ranged from 0.17 (beverages)-0.52 to 0.74 (rice), and Spearman's rank CCs with energy-adjustment ranged from 0.28 (confectionery)-0.42 to 0.68 (rice). Respective Pearson's CCs for intakes of nutrients were 0.28 (PUFAs)-0.51 to 0.73 (magnesium), and Spearman's rank CCs ranged from 0.23 (n-3 PUFAs)-0.45 to 0.71 (magnesium). Favorably higher agreement for intakes of foods/nutrients was achieved along with lower disagreement. CONCLUSIONS: Satisfactorily higher relative validity was attained in Japanese female dietitians with the SQFFQ. This calibrated questionnaire seems therefore appropriate for administration to Japanese dietitians to clarify associations between diet and health/disease. SPONSORSHIP: A grant-in-aid from the Ministry of Education, Science, Sports and Culture (06454242).

Adult↗
PubMed2001

CYP2C9*3 influences the metabolism and the drug-interaction of candesartan in vitro.

Candesartan cilexetil is an angiotensin II receptor antagonist, and candesartan, its active metabolite, is metabolized by CYP2C9. However, the effect of CYP2C9*3 on candesartan metabolism is not established. We characterized the kinetics of candesartan by CYP2C9*1/*1 and CYP2C9*1/*3 in human liver microsomes. The difference between the two was not significant. Subsequently, CYP2C9*1 and CYP2C9*3 (Leu359) were expressed in yeast, and the kinetics of candesartan were determined. The wild-type showed the lower Km (345 vs 439 microM; 3/4) and higher Vmax/Km (1/3) than the Leu359 variant. Also, we investigated potential interaction between candesartan and warfarin with both the wild-type and the Leu359 variant. Candesartan had no effect on S-warfarin 7-hydroxylation. In contrast, S-warfarin inhibited candesartan metabolism by the wild-type (K = 17microM) greater than by the Leu359 variant (Ki = 36 microM). These findings suggest that CYP2C9*3 may change not only the metabolic activity but also the inhibitory susceptibility compared with CYP2C9*1.

Alleles↗
PubMed2001

Expression of V-ATPase proteolipid subunit of Acetabularia acetabulum in a VMA3-deficient strain of Saccharomyces cerevisiae and its complementation study.

The function of the translation products of six different cDNAs for Acetabularia V-ATPase proteolipid subunit (AACEVAPD1 to AACEVAPD6) was examined using a Saccharomyces cerevisiae VMA3-deficient strain that lacked its own gene for one of the proteolipid subunits of V-ATPase. Expression of the cDNAs in the strain revealed that four cDNAs from the six complemented the proton transport activity into the vacuole, visualized by fluorescence microscopy. The vacuolar-membrane-enriched fractions from the four transformants showed cross-reactivity with antibodies against the subunits a and A of S. cerevisiae V-ATPase. Two translation products from the other two cDNAs were demonstrated not to be localized in vacuolar membranes, and thus could not complement the function of the VMA3-deficient strain. As the primary structures deduced from the former four cDNAs are similar but clearly different from those of the latter two, the latter two translation products may not be able to substitute for theVMA3 gene product.

Acetabularia↗
PubMed2001

Cell differentiation and apoptosis of monocytic and promyelocytic leukemia cells (U-937 and HL-60) by tryptanthrin, an active ingredient of Polygonum tinctorium Lour.

Tryptanthrin, a bioactive ingredient of Polygonum tinctorium Lour., is a member of the Indigo plant family and has potent cytocidal effects on various human leukemia cells in vitro. At low concentrations, tryptanthrin enhanced the expression of cell differentiation (CD) markers in human monocytic (U-937) and promyelocytic (HL-60) leukemia cells indicative of differentiation to monocytes/macrophages. Furthermore, nitroblue tetrazolium (NBT) reductive and alpha-naphthyl butyrate esterase (NBE) activities were markedly increased after treatment. Tryptanthrin was more potent than dimethyl sulfoxide (DMSO) at inducing U-937 cell differentiation into monocytes/macrophages. After treatment with higher concentrations of tryptanthrin for 24 h, cytoplasmic vacuolation and destruction of mitochondria were observed. The leukemia cells died via apoptosis 48 h after treatment. Cytoplasmic vacuolation and apoptotic changes correlated with the dysfunction of mitochondria. Electron microscopic observations revealed marked swelling and destruction of mitochondria after exposure of the leukemia cells to tryptanthrin. Exposure to tryptanthrin enhanced Fas-induced apoptosis and increased caspase-3 activity before induction of apoptosis. These results show that low concentrations of tryptanthrin can induce differentiation of leukemia cells but higher concentrations will kill leukemia cells through apoptosis, possibly through a caspase-3/Fas antigen pathway.

Antigens, CD↗