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Biomedical subjects

M Ikeda

Publications and source records attributed to M Ikeda.

At least 253 records · Page 14Linked to original sources
PubMed2001

Angiographic assessment of surgical reconstructions for left ventricular asynergy with indices of abnormally contracting segments.

BACKGROUND: In surgical reconstruction for left ventricular asynergy after myocardial infarction, the conventional linear closure technique second to simple resection and endoventricular circular patch plasty, which is the so-called Dor technique, are commonly utilized. We assessed these techniques using an abnormally contracting segment (ACS) in the left ventriculogram. METHODS: We reviewed 10 and 15 patients who underwent the linear technique (group L) and the Dor technique (group D), respectively. %ACS was determined as the percent ratio of both akinetic and dyskinetic chords among the total chords in the centerline method of regional wall motion analysis. A difference between preoperative and postoperative ejection fraction (EF) was generated by preoperative EF and this percentage ratio was determined as %EF. RESULTS: Postoperative EF improved from 31% to 41% in group L and from 33% to 49% in group D (p<0.05). Postoperative EF in group D was higher than in group L (p<0.05). %ACS decreased from 41% to 34% in group L and from 41% to 19% in group D (p<0.05). Postoperative %ACS was lower in group D than in group L (p<0.05). The significant correlation between preoperative %ACS and %EF was negative in group L and positive in group D (p<0.05). CONCLUSIONS: The Dor technique is more effective for the postoperative systolic function than the linear technique because more extensive reduction in %ACS is possible with the Dor technique than with the linear technique. Dor technique becomes more crucial to the postoperative systolic function as the preoperative %ACS becomes larger.

Aged↗
PubMed2000

Potential role of group X secretory phospholipase A(2) in cyclooxygenase-2-dependent PGE(2) formation during colon tumorigenesis.

Although the cyclooxygenase-2 (COX-2) pathway of the arachidonic acid cascade has been suggested to play an important role in colon carcinogenesis, there is little information concerning the identity of phospholipase A(2) (PLA(2)) involved in the arachidonic acid release in colon tumors. Here, we compared the potencies of three types of secretory PLA(2)s (group IB, IIA and X sPLA(2)s) for the arachidonic acid release from cultured human colon adenocarcinoma cells, and found that group X sPLA(2) has the most powerful potency in the release of arachidonic acid leading to COX-2-dependent prostaglandin E(2) (PGE(2)) formation. Furthermore, immunohistological analysis revealed the elevated expression of group X sPLA(2) in human colon adenocarcinoma neoplastic cells in concert with augmented expression of COX-2. These findings suggest a critical role of group X sPLA(2) in the PGE(2) biosynthesis during colon tumorigenesis.

Adenocarcinoma↗
PubMed2000

Association between two types of vitamin d receptor gene polymorphism and bone status in premenopausal Japanese women.

Polymorphisms in the vitamin D receptor (VDR) gene using ultrasound (US) bone mass and bone metabolic markers were investigated as potential genetic markers for osteoporosis in 126 premenopausal Japanese women aged 27.2 +/- 10.1 (mean +/- SD) years. The relationship between their VDR gene polymorphisms and bone states was determined. VDR genotypes were based on the absence (B) or presence (b) of the Bsm I restriction site (B polymorphism), and ATG (the M allele) and ACG (the m allele) sequences at the translation initiation site (M polymorphism). Genotype frequencies were 73.8%, bb; 24.6%, Bb; 1.6%, BB; 15.1%, MM; 51.6%, Mm and 33.3%, mm. The stiffness index of calcaneal bone minerals measured by an US bone densitometer was significantly higher in the mm types (P <0.05 versus MM) than in the Mm types (P <0.01 versus MM) and MM types. There was no significant difference between in B polymorphisms. Furthermore, bone mass was correlated with serum bone type alkaline phosphatase (ALP) activity and urinary deoxypyridinoline concentration in M polymorphisms. Because the distribution of B polymorphisms in each M polymorphism genotype did not differ, M polymorphisms were affected independently from B polymorphisms to bone mass or bone metabolic markers. No significant difference was observed in nutritional intake and food consumption among genotypes. In the MM and Mm types, the bone mass was closely related to the frequency of milk intake during the periods of elementary and junior high school. In contrast, bone mass was not associated with nutritional intake or the frequency of past milk intake in B polymorphisms. Therefore, the M polymorphism of the VDR gene is a stronger genetic indicator of osteoporosis than the B polymorphism in premenopausal Japanese woman.

Adult↗
PubMed2000

Indirubin inhibits inflammatory reactions in delayed-type hypersensitivity.

Polygonum tinctorium Lour. (P. tinctorium) is known to have the ability to suppress inflammation. We attempted to isolate the active compounds from P. tinctorium based on their inhibitory effects on the production of interferon-gamma, which is a well-known inflammatory cytokine. We thus isolated indirubin, an isomer of indigo. Indirubin exerted its inhibitory effects not only on interferon-gamma production by human myelomonocytic HBL-38 cells but also on interferon-gamma and interleukin-6 production by murine splenocytes with no influence on the proliferation of either cells. Because of its inhibitory activity on interferon-gamma production, we further investigated the effects of indirubin on 2,4, 6-trinitro-l-chlorobenzene (TNCB)-induced delayed-type hypersensitivity as a representative inflammatory reaction. When injected intraperitoneally, indirubin significantly inhibited the ear swelling of TNCB-elicited mice. The amount of interferon-gamma in the culture supernatants of elicited mouse lymphocytes was inhibited by indirubin treatment. These results suggest that indirubin is a compound with anti-inflammatory effects.

Adjuvants, Immunologic↗
PubMed2000

Shiga toxin activates p38 MAP kinase through cellular Ca(2+) increase in Vero cells.

We examined whether the mitogen-activated protein kinase (MAPK) pathway is involved in Shiga toxin (Stx)-induced Vero cell injury. Consonant with cell injury, Stx caused a transient extracellular signal-regulated kinase1/2 (ERK1/2) and a sustained p38 MAPK phosphorylation. p38 MAPK inhibitors (SB 203580 and PD 169316), but not an ERK1/2 kinase inhibitor (PD 98059), partially inhibited the Stx-induced cell death. BAPTA-AM, a Ca(2+) chelator, reduced both cell injury and p38 MAPK phosphorylation. Antioxidants reduced Stx1-induced p38 MAPK phosphorylation. These data indicate that Stx activates p38 MAPK through an increase in intracellular Ca(2+) and reactive oxygen species, and this signaling is involved in Stx-induced cell death.

Animals↗
PubMed2000

A unique dosage form to evaluate the mechanical destructive force in the gastrointestinal tract.

The purpose of this study was to prepare tablets that could evaluate the destructive force in the gastrointestinal (GI) tract. Many factors are known to affect in vivo drug release from oral dosage forms. There is still relatively little information on the mechanical destructive force in the GI tract. Press-coated tablets with an extremely brittle outer layer were developed using a unique, highly hydrophobic Teflon powder that could be shaped with weak compression force. A marker drug contained in the tablets was released only when the tablets received a force larger than its predetermined crushing strength. We referred to this type of tablet as a 'destructive force dependent release system' (DDRS). A total of nine healthy, male subjects were orally administered the tablets under fed and/or fasting conditions. Tablets with a predetermined crushing strength of 1.50 N were crushed by all of the four subjects who took them under fed conditions and two of the five subjects under fasting conditions. Tablets with a crushing strength of 1.89 N were crushed by two of the six subjects who took them under fed conditions and none of the five subjects under fasting conditions. The range of mechanical destructive force in the human stomach was obtained.

Adult↗
PubMed2000

Tryptanthrin inhibits nitric oxide and prostaglandin E(2) synthesis by murine macrophages.

Nitric oxide (NO) and prostaglandins have been implicated in the pathogenesis of several inflammatory diseases. In this study, we investigated the effect of tryptanthrin (6,12-dihydro-6, 12-dioxoindolo-(2,1-b)-quinazoline), an antimicrobial and antitumoral plant compound isolated from Porigonum tinctorium, on NO and prostaglandin E(2) production by interferon-gamma and lipopolysaccharide-stimulated murine macrophage-like RAW 264.7 cells. Tryptanthrin markedly inhibited both NO and prostaglandin E(2) production in a dose-dependent manner. Tryptanthrin at 20 microM fully inhibited expression of inducible NO synthase, suggesting that the inhibitory effect on NO synthesis was mediated by inhibited expression of the enzyme. On the other hand, tryptanthrin had no effect on the levels of cyclooxygenase-2 protein, but inhibited cyclooxygenase enzyme activity with a ICM(50) value of 1.5 microM. Thus, tryptanthrin has the dual functions of inhibiting both NO and prostaglandin E(2) production by activated macrophages, suggesting that tryptanthrin exhibits anti-inflammatory properties.

Animals↗
PubMed2000

Impaired neurotransmitter systems by Abeta amyloidosis in APPsw transgenic mice overexpressing amyloid beta protein precursor.

APPsw transgenic mice showing substantial features of brain Abeta amyloidosis such as senile plaques and behavioral abnormalities were examined by immunostaining to determine whether Abeta deposits could induce the subsequent disturbance of neurotransmitter systems including somatostatin, substance P and choline acetyltransferase (ChAT), which are prominent in the Alzheimer's disease brain. Somatostatin, substance P and ChAT disappeared in the areas of senile plaque and were accumulated in dystrophic neurites around the amyloid cores. These findings suggest a potential role of brain Abeta amyloidosis in disturbance of the neurotransmitter systems leading to memory disturbance of Alzheimer's disease.

Amygdala↗
PubMed2000

Effects of sodium and potassium channel blockers on hyperinflation-induced slowly adapting pulmonary stretch receptor stimulation in the rat.

The excitatory responses of slowly adapting pulmonary stretch receptor (SAR) activity to hyperinflation (inflation volume = 3 tidal volumes) for approximately 10 respiratory cycles were examined before and after administration of flecainide, a Na+ channel blocker, and 4-aminoprydine (4-AP), a K+ channel blocker. The experiments were performed in anesthetized, artificially ventilated rats after unilateral vagotomy. During hyperinflation the SARs increased their activity during inflation and decreased their discharge during deflation. The magnitude of increased SAR activity during inflation became more prominent as compared to that of decreased receptor activity during deflation. Flecainide treatment (6 mg/kg) that was sufficient to block veratridine (50 microg/kg)-induced SAR stimulation did not significantly alter the excitatory response of SAR activity to hyperinflation. Subsequent administration of 3 mg/kg flecainide (a total dose, 9 mg/kg) resulted in a greater inhibition of hyperinflation-induced SAR stimulation. Although administration of 4-AP (2 mg/kg) usually stimulated SAR activity, particularly in the deflation phase, in the control ventilation, 4-AP treatment had no significant effect on hyperinflation-induced SAR stimulation. These results suggest that the excitatory effect of hyperinflation on SAR activity may not be involved in the activation of either flecainide-sensitive Na+ channels or 4-AP-sensitive K+ channels.

Animals↗
PubMed2000

N-methyl-D-aspartate receptor subtype 2C is not involved in circadian oscillation or photoic entrainment of the biological clock in mice.

Ishida et al. [1994: Neurosci Lett 166: 211-215] reported the circadian change of N-methyl-D-aspartate (NMDA) receptor subtype 2C mRNA and photic induction of this receptor's mRNA in the suprachiasmatic nucleus (SCN). Therefore, we investigated the role of NMDA receptor subtypes in the biological clock using NMDA receptor 2A (NR2A)- or 2C (NR2C)-deficient mice. However, NR2C-/- mice showed normal light-dark (LD)-entrained locomotor activity rhythms and free-running rhythms under constant darkness and also exhibited normal reentrainment to 6-hr LD shifts and phase delays with single light pulses. Thus, present results demonstrated no significant NR2C contribution to circadian oscillation and photic entrainment, even though expression of NR2C mRNA was highly observed in the SCN. On the other hand, the period of the free-running activity rhythm in NR2A-/- mice but not NR2C-/- mice was slightly longer than that in wild-type mice in spite of low expression of NR2A in the SCN. Furthermore, reentrainment to an LD advance in NR2A-/- mice was slower under low-intensity light conditions. Thus, we suggest that NR2A plays a role in determining the behavioral state that affects the circadian rhythm. In order to elucidate the role of NR2A and NR2C in the SCN, we examined NMDA-induced Ca(2+) elevations in the SCN of mutant mice using a Ca(2+) imaging method. A partial reduction in Ca(2+) elevation was observed in both NR2A-/- and NR2C-/- mice when high concentrations (100 or 300 microM) of NMDA were applied. The present results suggest that NR2A plays a weak role in oscillation or entrainment of the biological clock, and that NR2C does not participate in the functions of circadian oscillation and light entrainment.

Animals↗
PubMed2000

Administration of melatonin in drinking water promotes the phase advance of light-dark cycle in senescence-accelerated mice, SAMR1 but not SAMP8.

We analyzed effects of aging on behavioral rhythms in the mouse showing senescence acceleration, SAMP8 strains. The free-running rhythms had longer free-running periods (tau) in SAMP8 than in the control strain (SAMR1). Drinking of melatonin promoted the adaptation to advanced LD in SAMR1 but not in SAMP8, although both strains exhibited melatonin MT1 and MT2 receptors. The present results suggest that melatonin promotes the adaptation to advanced LD cycles in normal aging mice.

Adaptation, Physiological↗
PubMed2000

Mouse group X secretory phospholipase A2 induces a potent release of arachidonic acid from spleen cells and acts as a ligand for the phospholipase A2 receptor.

Group X secretory phospholipase A2 (sPLA2-X) has recently been shown to possess a powerful potency for releasing arachidonic acid from cell membrane phospholipids. Here, we report the purification of mouse pro- and mature forms of sPLA2-X, as well as its expression and biological functions. Purified pro-sPLA2-X was found to possess a propeptide of 11 amino acid residues attached at the NH2-terminals of the mature protein, and showed as little as 8% of the PLA2 activity of the mature form. Limited proteolysis of pro-sPLA2-X with trypsin resulted in the appearance of the mature form with a concomitant increase in PLA2 activity, suggesting a requirement of proteolytic removal of the propeptide for the optimal activity. The expression of sPLA2-X mRNA was detected in various tissues including the lung, thymus, and spleen, and immunohistochemical analysis revealed its expression in splenic macrophages. In the spleen cells, mature sPLA2-X elicited a prompt release of arachidonic acid with significant production of prostaglandin E2 more efficiently than group IB and IIA sPLA2s. In addition, sPLA2-X was identified as a high-affinity ligand for both native and recombinant form of mouse PLA2 receptor (PLA2R). However, there was no significant difference in the sPLA2-X-induced arachidonic acid release responses in the spleen cells between wild-type and PLA2R-deficient mice. These findings strongly suggest that sPLA2-X possesses two distinct biological functions in mice: it elicits a marked release of arachidonic acid from membrane phospholipids leading to the production of lipid mediators based on its enzymatic potency, and it acts as a natural ligand for the PLA2R that has been shown to play a critical role in the production of inflammatory cytokines during endotoxic shock.

Animals↗
PubMed2000

cDNA cloning of a novel bHLH-PAS transcription factor superfamily gene, BMAL2: its mRNA expression, subcellular distribution, and chromosomal localization.

We isolated a human cDNA encoding a novel member of the bHLH-PAS transcription factor superfamily, BMAL2, which is highly similar to, but distinct from, BMAL1. The composite cDNA covered a 1720-bp sequence consisting of a putative 1653-bp open reading frame encoding a polypeptide of 551 amino acids. The deduced BMAL2 product contains a bHLH-PAS domain in its N-terminal region and a variable C-terminus. The overall identity of BMAL2 polypeptide to that of human BMAL1 is 49%. RNA analysis revealed that expression of BMAL2 transcripts was restricted to the fetal brain and to the adult liver in human, while human BMAL1 mRNA was expressed in the brain and skeletal muscle. The chromosomal localization of the human BMAL2 gene was determined by fluorescent in situ hybridization to be localized on chromosome 12 at region p12.2-p11.2. These results suggest that BMAL2 may play different roles from BMAL1 in the embryonic brain and in adult mammals.

Adult↗
PubMed2000

Inhibitory mechanism of slowly adapting pulmonary stretch receptors after release from hyperinflation in anesthetized rabbits.

In anesthetized, artificially ventilated rabbits with vagus nerve section, release from 10 consecutive hyperinflations (inflation volume = 3 tidal volume) caused an inhibition of the slowly adapting pulmonary stretch receptor (SAR) activity for 16-22 sec. Intravenous administration of tetraethylammonium (TEA, 10 and 20 mg/kg), a K+ channel blocker, did not significantly alter either basal SAR discharge or tracheal pressure (PT). Although TEA treatment at 10.0 mg/kg had no significant effect on the magnitude and duration of inhibited SAR activity seen after release from hyperinflation, the increasing dose of this K+ channel blocker up to 20 mg/kg inhibited these effects of the receptor activity but this inhibition was small. The Na+ -K+ ATPase inhibitor ouabain (5 and 10 microg/kg) that had no significant effect on SAR activity and P(T) in the control abolished or attenuated the inhibitory action of SARs in a dose-dependent manner. Furthermore, the changes in dynamic lung compliance (Cdyn) and P(T) in response to post-hyperinflation were not significantly influenced by pretreatment with either TEA or ouabain. These results suggest that the inhibitory action of receptors seen during post-hyperinflation corresponded with the induction of slow afterhyperpolarization (sAHP), and that the mechanism of generating the sAHP of SARs is mainly mediated by the activation of Na+ -K+ pump activity.

Adaptation, Physiological↗
PubMed2000

Suppression of carbonic anhydrase III in rat liver by a dioxin-related toxic compound, coplanar polychlorinated biphenyl, 3, 3',4,4',5-pentachlorobiphenyl.

A coplanar polychlorinated biphenyl, 3,3',4,4',5-pentachlorobiphenyl (PenCB), significantly suppresses the expression of rat liver carbonic anhydrase III (CAIII), an enzyme which has recently been suggested to prevent from H(2)O(2)-inducible apoptosis. Marked changes in the CAIII levels of liver cytosol were observed in rats following doses of PenCB ranging from 0.5 to 25 mg/kg body weight and maximum suppression was observed at a dose of 10 mg/kg. Northern analysis revealed that the level of CAIII mRNA in rat liver was dramatically reduced by PenCB treatment while only weak suppression was observed in pair-fed controls. Two AU-rich elements, considered as a destabilizing signal of mRNA, were found in the 3'-untranslated region of CAIII sequenced after reverse transcription-PCR and 3'-rapid amplification of the cDNA end. Dramatic decrease of CAIII in rat liver by PenCB could account for the suppression of the defense system for oxidative stress.

3' Untranslated Regions↗
PubMed2000

Enhanced tissue expression and elevated circulating level of phospholipase A(2) receptor during murine endotoxic shock.

Phospholipase A(2) receptor (PLA(2)R) mediates a variety of biological responses elicited by mammalian secretory phospholipase A(2) (sPLA(2)). In mice, group IB sPLA(2) (sPLA(2)-IB) acts as an endogenous ligand of PLA(2)R, and analysis of PLA(2)R-deficient mice has demonstrated a critical role of the sPLA(2)-IB/PLA(2)R system in the production of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha) in the development of endotoxic shock. Here, we generated specific antibodies against a recombinant soluble form of PLA(2)R and examined its expression in the lung and spleen where a remarkable elevation of TNF-alpha expression has been observed during endotoxemia. Immunohistochemical analysis revealed the expression of PLA(2)R in type II alveolar epithelial cells and a subset of splenic lymphocytes, and its expression levels were markedly enhanced at 1 h after endotoxin challenge. Analysis with a newly developed sandwich enzyme-linked immunosorbent assay system revealed the presence of a soluble form of PLA(2)R in plasma of wild-type mice compared with its absence in plasma of PLA(2)R-deficient mice. After exposure to endotoxin, its circulating level was significantly elevated to the maximum level at 2-3 h after the treatment. These results suggest that tissue expression and the circulating level of PLA(2)R are elevated during murine endotoxemia, which might be relevant to its potential roles in the production of proinflammatory mediators during the development of inflammatory conditions.

3T3 Cells↗