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Biomedical subjects

M Ikeda

Publications and source records attributed to M Ikeda.

At least 793 records · Page 44Linked to original sources
PubMed1996

Regulation of cytokine production by sugi allergen-pullulan conjugate.

Sugi basic protein (SBP), a major allergen of Japanese cedar (Cryptomeria japonica) pollen, conjugated to pullulan (alpha-1,4'-, alpha-1,6'-glucan) reportedly suppresses IgE anti-SBP antibody production and enhances IgG anti-SBP antibody production in mice. We analyzed cytokine production by SBP-specific T cells after stimulation with an SBP-pullulan conjugate (SBP-P), native SBP, or a mixture of SBP and pullulan. When SBP-specific T cell lines were stimulated with the SBP-P conjugate in the presence of antigen-presenting cells (APC), the production of IFN-gamma, IL-4, IL-5, and IL-10 decreased compared with the cytokine levels produced by SBP-stimulated T cells. However, when these T cells were repeatedly stimulated with the SBP-P conjugate, the production of IFN-gamma increased progressively, while that of IL-4, IL-5, and IL-10 remained decreased compared with the T cells that were repeatedly stimulated with native SBP. Stimulation of the T cells with the mixture of SBP and pullulan showed little difference in the cytokine production profile from that observed after stimulation with native SBP alone. Interestingly, when the T cell lines stimulated repeatedly with SBP-P were subsequently stimulated with native SBP, a further increase in IFN-gamma production was observed, while IL-10 production decreased. Inhibition of IL-4 production was also observed when SBP-specific Th2 clones were stimulated with SBP-P. These results indicate that stimulation of T cells with SBP-P up-regulates Th1 cytokine production, while down-regulating that of Th2. It is, therefore, conceivable that immunotherapeutic treatment with the SBP-P conjugate rather than with conventional SBP solutions is preferable for improving Japanese cedar pollen allergy.

Allergens↗
PubMed1996

Nitric oxide synthase-containing neurons in the hippocampus are preserved in trimethyltin intoxication.

We studied the effects of trimethyltin (TMT) (9 mg/kg, p.o.) on the nitric oxide synthase (NOS)-containing neurons in the rat hippocampus by NADPH-diaphorase histochemistry and a biochemical assay of NOS activity. TMT exposure caused the typical behavioral changes and a loss of the CA3/4 pyramidal cells, which were NADPH diaphorase-negative. The scattered interneurons and the CA1 pyramidal cells, which were NADPH diaphorase-positive, were spared. Hippocampal NOS activity showed no reduction in the TMT-treated rats compared with the controls. These results provide evidence of the preservation of the NOS-containing neurons in TMT intoxication.

Animals↗
PubMed1996

[Reliability of the evaluation of the active sweat gland density on the dorsum of the foot using the silastic impression mold technique].

The evaluation of the density of the active sweat gland on the dorsum of the foot induced by iontophoresis of 1% pilocarpine was made repeatedly using the silastic impression mold technique in 83 subjects (52 normal volunteers: 24 subjects younger than 50 years of age and 28 subjects 50 years of age or older, 20 men and 32 women: 20 diabetic patients and 11 patients with other neurological disorders), from 12 to 82 years of age, and the reliability of such evaluation was assessed. After 8 to 14 days following the first evaluation, the second one was performed. The reliability was expressed as an intra-class correlation. The intra-class correlation was greater in the subjects 50 years of age or older (0.909) than in the subjects younger than 50 years of age (0.653). It was similar between males (0.921) and females (0.803). On the other hand, it was less in diabetic patients (0.543) than in the normal volunteers (0.857) and patients with other neurological disorders (0.809). The silastic impression mold technique is widely applicable in evaluating the sweat gland function. However, it should be kept in mind that the reliability is variable among the groups defined clinically and that it is low in the diabetic patients.

Adolescent↗
PubMed1996

Role of platelet-activating factor and thromboxane A2 in radical production during ischemia and reperfusion of the rat brain.

Oxygen radicals produced by activated neutrophils have been involved in brain injury during ischemia-reperfusion. Platelet-activating factor (PAF) is a candidate as one of the mediators of neutrophil activation during cerebral ischemia-reperfusion. Recent evidence indicates that PAF-induced neutrophil activation is mediated by thromboxane A2 (TXA2). To study the role of PAF and TXA2 in radical production during cerebral ischemia-reperfusion, we evaluated the effects of a PAF antagonist, Y-24180, and a TXA2 antagonist, S-1452, on radical formation in rats with 1 h middle cerebral artery (MCA) occlusion. In the present study, we employed a new electron spin resonance (ESR) method coupled with brain microdialysis. The method uses the endogenous ascorbyl radical (AR) concentration as a marker of oxygen radicals and requires no spin-trapping agents. In the vehicle controls, extracellular AR from the ischemic brain cortex decreased during MCA occlusion. Following reperfusion, AR significantly increased at 30 mm and 1 h, returned to near the basal levels at 2 h, and increased again at 24 h after reperfusion. In the rats treated with S-1452 or Y-24180, AR decreased during MCA occlusion to the same extent as in the vehicle control. However, pretreatment with Y-24180 or S-1452 significantly attenuated the increase in extracellular AR after reperfusion, while it exerted no effect on the changes in extracellular ascorbate or tissue pO2 throughout the experimental period. In conclusion, PAF and TXA2 might contribute to cerebral ischemia-reperfusion injury by increasing the generation of oxygen radicals.

Animals↗
PubMed1996

Isolation and characterization of cDNA for DREF, a promoter-activating factor for Drosophila DNA replication-related genes.

DREF, a transcription regulatory factor which specifically binds to the promoter-activating element DRE (DNA replication-related element) of DNA replication-related genes, was purified to homogeneity from nuclear extracts of Drosophila Kc cells. cDNA for DREF was isolated with the reverse-transcriptase polymerase chain reaction method using primers synthesized on the basis of partial amino acid sequences and following screening of cDNA libraries. Deduced from the nucleotide sequences of cDNA, DREF is a polypeptide of 701 amino acid residues with a molecular weight of 80,096, which contains three characteristic regions, rich in basic amino acids, proline, and acidic amino acids, respectively. Deletion analysis of bacterially expressed DREF fused with glutathione S-transferase (GST-DREF) indicated that a part of the N-terminal basic amino acid region (16-115 amino acids) is responsible for the specific binding to DRE. A polyclonal and four monoclonal antibodies were raised against the GST-DREF fusion protein. The antibodies inhibited specifically the transcription of DNA polymerase alpha promoter in vitro. Cotransfection experiments using Kc cells demonstrated that overproduction of DREF protein overcomes the repression of the proliferating cell nuclear antigen gene promoter by the zerknüllt gene product. These results confirmed that DREF is a trans-activating factor for DNA replication-related genes. Immunocytochemical analysis demonstrated the presence of DREF polypeptide in nuclei after the eighth nuclear division cycle, suggesting that nuclear accumulation of DREF is important for the coordinate zygotic expression of DNA replication-related genes carrying DRE sequences.

Amino Acid Sequence↗
PubMed1996

Ras-interacting domain of RGL blocks Ras-dependent signal transduction in Xenopus oocytes.

RalGDS family members (ralGDS and RGL) interact with the GTP-bound form of Ras through its effector loop. The C-terminal region (amino acids 602-768) of RGL is responsible for binding to Ras. In this paper we characterized a Ras-interacting domain of RGL using deletion mutants of RGL(602-768). RGL(602-768), RGL(632-768), and RGL (602-734) bound to the GTP-bound form of Ras and inhibited the GAP activity of NF-1. RGL(646-768) showed a low binding activity to Ras and inhibited GAP activity of NF-1 weakly. None of RGL(659-768), RGL(685-768), RGL(602-709), and RGL(602-686) bound to Ras or inhibited GAP activity of NF-1. These results indicate that amino acids 632-734 of RGL constitute a nearly minimal domain that contains the binding element for Ras. RGL(632-734) inhibited v-Ras- but not progesterone-induced Xenopus oocyte maturation. Furthermore, RGL(632-734) inhibited v-Ras- but not v-Raf- dependent extracellular signal-regulated kinase activation in Xenopus oocytes. These results clearly demonstrate that the Ras-interacting domain of RGL is important for Ras-dependent signal transduction in vivo.

Animals↗
PubMed1996

Nonpeptide angiotensin II receptor antagonists: synthesis, biological activities, and structure-activity relationships of imidazole-5-carboxylic acids bearing alkyl, alkenyl, and hydroxyalkyl substituents at the 4-position and their related compounds.

A series of imidazole-5-carboxylic acids bearing alkyl, alkenyl, and hydroxyalkyl substituents at the 4-position and their related compounds were prepared and evaluated for their antagonistic activities to the angiotensin II (AII) receptor. Among them, the 4-(1-hydroxyalkyl)-imidazole derivatives had strong binding affinity to the AII receptor and potently inhibited the AII-induced pressor response by intravenous administration. Various esters of these acids showed potent and long-lasting antagonistic activity by oral administration. The most promising compounds were (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl (CS-866) and (pivaloyloxy)-methyl esters of 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[(2'-1H-tetrazol-5- ylbiphenyl-4-yl)-methyl]imidazole-5-carboxylic acid (26c). A study involving stereochemical comparison of 26c with the acetylated C-terminal pentapeptide of AII was also undertaken.

Acetylation↗
PubMed1996

Plasma endothelin level in the acute stage of Bell palsy.

OBJECTIVE: To determine the plasma endothelin level in the acute stage in patients with Bell palsy (based on the hypothesis that endothelin, which is a potent vasoconstrictor, may play a role in the mechanism of the onset of facial nerve paralysis and in view of the fact that the etiology of Bell palsy is still a maze of unknowns). DESIGN: The study involved 62 patients with the acute stage (tested within 10 days of onset) of Bell palsy (i.e., idiopathic acute peripheral facial paralysis) and an additional 36 healthy persons who served as control subjects. To determine the content of endothelin, 2 ml of plasma samples was collected from each subject. Endothelin-1 was extracted and analyzed by a radioimmunoassay by using anti-endothelin-1 antibody. SETTING: Nihon University Itabashi Hospital, a referral and institutional center in Tokyo, Japan. RESULTS: The patients who were suffering from Bell palsy exhibited a statistically significant (P < .01) increase in the endothelin level compared with that in the 36 normal control subjects. An age-matched comparison (ranges, 20-29 years and 30-39 years) of patients with Bell palsy with normal control subjects revealed a significant difference between the normal group and the group with Bell palsy in the plasma endothelin level for both age groups that were tested (P < .01). The mean value of the endothelin level in patients with Bell palsy was maximal on day 5, and the percentage of patients with abnormally elevated endothelin levels was 100% from days 6 to 9. CONCLUSION: Endothelin, which has potent vasoconstrictive effects, may contribute to the pathogenesis of the microcirculatory impairment that occurs in patients with Bell palsy, mainly by promoting secondary ischemia.

Acute Disease↗
PubMed1996

Simultaneous digital imaging analysis of cytosolic calcium and morphological change in platelets activated by surface contact.

The dynamic change of cytoplasmic Ca(2)+ concentration ([Ca(2)+]i) and morphological change were investigated simultaneously by confocal laser scanning microscopy using fluo-3 and by differential interference contrast optics in platelets activated by contact with the following types of surfaces: native glass and glass treated with poly-L-lysine (PLL), fibrinogen (Fg), or von Willebrand factor (vWF). The initial [Ca(2)+]i values just after the surface contact were comparable (approximately 100 nM) among platelets deposited on the four surface types. On the PLL-surface, no morphological change or [Ca(2)+]i elevation was observed. Glass-, Fg-, and vWF-surface adhered platelets showed pseudopod formation and spreading associated with the inhomogeneous [Ca(2)+]i rise. The platelets on the Fg-surface were the most active in terms of [Ca(2)+]i rise and morphological change. During pseudopod formation, the mean [Ca(2)+]i value was maximal and localized high [Ca(2)+]i zones were observed inside pseudopods, as well as in the center of the platelets. After spreading, high [Ca(2)+]i zones still remained in the center of the cell. This new technique enabled simultaneous observation of [Ca(2)+]i and cell shape and we clearly demonstrated a close relationship between [Ca(2)+]i and morphological alterations.

Analog-Digital Conversion↗
PubMed1996

Separate analysis of nuclear and cytosolic Ca2+ concentrations in human umbilical vein endothelial cells.

Ca2+ concentration inside human umbilical vein endothelial cells was studied separately in cytosol and nucleus by a confocal laser scanning microscopy using fluo-3. The in vivo calibration curve for cytosol and nucleus showed good linearity between fluorescence intensity and Ca2+ concentration in cytosol ([Ca2+]i) and nuclei ([Ca2+]n). After calibration, [Ca2+]n was constantly higher than [Ca2+]i before and after the chelation of extracellular Ca2+ suggesting an active Ca2+ accumulation system on nuclear membrane. [Ca2+]n was also constantly higher than [Ca2+]i after the stimulation of thrombin (0.05 U/ml), FCS (10%), and thapsigargin (Tsg, 1 microM). The temporal change of [Ca2+]n and [Ca2+]i was identical, and [Ca2+]i gradient towards the nucleus and peripheral or central [Ca2+]n rise was observed after these stimulations. From these results, [Ca2+]n is not only regulated by the active Ca2+ accumulation system on nuclear membrane at rest but also the generation of inositol-triphosphate. FCS caused heterogeneous [Ca2+]n or [Ca2+]i rise from cell to cell; single spike or oscillatory change of [Ca2+]n and [Ca2+]i was observed in about 56% of cells, which were completely abolished by the chelation of extracellular Ca2+, suggesting that FCS stimulated [Ca2+]n and [Ca2+]i rise solely depending on Ca2+ influx from extracellular medium. The higher concentration of [Ca2+]n and heterogeneous [Ca2+]n rise may have important roles in nuclear-specific cellular responses.

Aniline Compounds↗
PubMed1996

Lipid emulsions of palmitoylrhizoxin: effects of composition on lipolysis and biodistribution.

Four types of lipid emulsion for highly lipophilic antitumour agent RS-1541 (13-O-palmitoylrhizoxin) with mean particle diameters of 200-260 nm were prepared using soybean oil (SOY) or dioctanoyldecanoylglycerol (ODO) for the oil phase and lecithin (LEC) or polyoxyethylene-(60)-hydrogenated castor oil (HCO-60) for surfactants. The lipolysis rate of HCO-60-emulsified emulsions by lipoprotein lipase was much slower than that of LEC-emulsified emulsions. Particle sizes of emulsions incubated in plasma with the lipase for six hours were 75%, 79%, 101%, and 93% of initial values for SOY/LEC, ODO/LEC, SOY/HCO-60, and ODO/HCO-60 emulsions, respectively, showing an apparent size decrease for LEC-emulsified emulsions. In rats, uptake clearance values of SOY/LEC and ODO/LEC emulsions of RS-1541 in the reticuloendothelial system (RES) were 81.2 and 135.3 mL h(-1), respectively, and AUC values were 4.0 and 1.3 microg h mL(-1), respectively. In contrast, RES uptake clearances of HCO-60 emulsions of RS-1541 were considerably lower (4.2 mL h(-1) for SOY/HCO-60; 2.2 mL h(-1) for ODO/HCO-60), resulting in high AUC values (35.4 microg h mL(-1) for SOY/ HCO-60; 63.9 microg h mL(-1) for ODO/HCO-60). The concentrations of RS-1541 in tumour tissues after an intravenous administration of ODO/HCO-60 emulsions of RS-1541 to mice bearing solid tumour M5076 sarcoma were about ten times higher than those after the administration of SOY/LEC emulsions. These results indicate that HCO-60 emulsions, compared with conventional LEC emulsions, are more stable to lipoprotein lipase and show low uptakes by RES organs, long circulations in the plasma, and high distributions in tumours. Thus, these sterically stabilized emulsions could show potential as effective carriers for highly lipophilic antitumour agents to enhance the drug delivery in tumours.

Animals↗
PubMed1996

Lipid emulsions of palmitoylrhizoxin: effects of particle size on blood dispositions of emulsion lipid and incorporated compound in rats.

Emulsion formulations of various particle sizes for the highly lipophilic antitumour agent, RS-1541 (13-O-palmitoylrhizoxin), were prepared using dioctanoyldecanoylglycerol (ODO) as lipids and polyoxyethylene-(60)-hydrogenated castor oil (HCO-60) as a surfactant. These emulsions were evaluated as injectable drug carriers and compared with a colloidal solution. Both in vitro and in vivo after i.v. administration, RS-1541 was distributed into lipoproteins from the colloidal solution. When applied as emulsions of various particle sizes (124-419 nm) in vitro, RS-1541 was retained and stabilized within the emulsions. In the in vivo study, however, retention of RS-1541 in the emulsions after i.v. injection depended on their size. The small-particle emulsions (94-112 nm) resulted in long retention, and the large-particle emulsions (415-474 nm) led to short retention. Lipolysis rates of emulsion particles by lipoprotein lipase also depended on their size, indicating rapid lipolysis for small-particle emulsions (133 nm). However, the lipolysis was not such an extensive one, showing 10-30% release of capric acid from ODO within 6 h. Blood dispositions of capric acids approximately paralleled those of RS-1541 after i.v. injection of various particle size emulsions (130-368 nm) to rats, although relatively rapid eliminations of capric acids compared with RS-1541 were observed for the small-particle size emulsions (130 nm). These results suggest that when injected as emulsion formulations, the highly lipophilic antitumour agent, RS-1541, has behaviour similar to that of the emulsion particles in the body, which is dependent on the size of the latter. Thus, by properly selecting the particle size, lipid emulsions consisting of ODO and HCO-60 are expected to be effective and useful DDS carriers for RS-1541.

Animals↗
PubMed1996

The clinical phenotype of two missense mutations in the presenilin I gene in Japanese patients.

We report the clinical and neuropathologic phenotypes associated with two different missense mutations in the presenilin 1 (PS-1) gene in Japanese patients with early-onset familial Alzheimer's disease (FAD). In the AM/JPN1 pedigree a missense mutation (C-->T) was found at nucleotide 1102, which is predicted to cause an alanine-to-valine missense substitution at codon 260. In this family, the disease had a mean age of onset of 40.3 years and an indolent course (range, 8-19 years). Neuropathologic studies in 3 members of this pedigree showed widespread senile plaques, neurofibrillary tangles, and neuronal loss, as well as abundant perivascular subpial amyloid deposits in the Virchow-Robin spaces and the presence of Pick-like intraneuronal inclusions in the dentate gyrus. In the second pedigree, transmitting a C-->T nucleotide substitution at position 1027, leading to the missense mutation of alanine to valine at codon 285, the disease had a later onset (mean, 51 years) but a more rapid course. Comparison of the disease phenotypes associated with other missense mutations in exon 9 of PS-1 reveals no clinical or pathological phenotype, which uniquely distinguishes Alzheimer's disease associated with PS-1 mutations from other forms of early-onset FAD, implying that direct mutation screening is required to identify these cases.

Adult↗
PubMed1996

Interferon-gamma-inducing factor enhances T helper 1 cytokine production by stimulated human T cells: synergism with interleukin-12 for interferon-gamma production.

The novel cytokine interferon-gamma-inducing factor (IGIF) augments natural killer (NK) cell activity in cultures of human peripheral blood mononuclear cells (PBMC), similarly to the structurally unrelated cytokine interleukin (IL)-12. IGIF has been found to enhance the production of interferon-gamma (IFN-gamma) and granulocyte/macrophage colony-stimulating factor (GM-CSF) while inhibiting the production of IL-10 in concanavalin A (Con A)-stimulated PBMC. In this study, when anti-CD3 monoclonal antibody (mAb)-stimulated human enriched T cells were exposed to IGIF, the cytokine dose-dependently enhanced the proliferation of the cells and this could be completely inhibited by a neutralizing antibody against IL-2 at lower concentrations of IGIF. Neutralizing antibody against IFN-gamma had only insignificant inhibitory effects on T cell proliferation at higher concentrations of IGIF. Enzyme-linked immunosorbent assays (ELISA) revealed that, like PBMC, T cells exposed to IGIF produced large amounts of IFN-gamma; however, changes in the production of IL-4 and IL-10 were minimal. IGIF, but not IL-12, significantly enhanced IL-2 and GM-CSF production in T cell cultures, as determined by CTLL-2 bioassay and ELISA, respectively; however, both IGIF and IL-12 enhanced IFN-gamma production by the T cells. When T cells were exposed to a combination of IGIF and IL-12, a synergistic effect was observed on the production of IFN-gamma, but not on production of IL-2 and GM-CSF. In conclusion, IGIF enhances T cell proliferation apparently through an IL-2-dependent pathway and enhances Th1 cytokine production in vitro and exhibits synergism when combined with IL-12 in terms of enhanced IFN-gamma production but not IL-2 and GM-CSF production. Based on structural and functional differences from any known cytokines, it was recently proposed that this cytokine be designated interleukin-18.

Adult↗
PubMed1996

Protein degradation in human pure pancreatic juice analyzed by two-dimensional gel electrophoresis.

Two-dimensional gel electrophoresis (2-DE) was used to study protein degradation in human pure pancreatic juice (PPJ) which was collected at 5 min intervals for 20 min by selective endoscopic cannulation of the main pancreatic duct. In PPJ collected from healthy subjects no significant degradation was observed by incubating PPJ at 37 degrees C up to 6 h. By further incubation for 24 h, glycoprotein-1, procarboxypeptidase A-1 and lipase were nearly completely degraded, while alpha-amylase and procarboxypeptidase B-1 were not degraded under these conditions; alpha-amylase became labile in the presence of 1 mM ethylene diaminetetraacetic acid (EDTA) or 10 mM phenyl methyl sulfonyl fluoride (PMSF). Protein degradation was observed by 2-DE of an initial fraction of PPJ collected from patients with chronic calcific pancreatitis (CCP). The 2-DE patterns of subsequent fractions resembled those of PPJ from healthy subjects. The mixture of the last fraction with the initial fraction showed significant protein degradation, inhibited by adding aprotinin. Furthermore, the extent of protein degradation correlated with the dilatation of the main pancreatic duct as a consequence of intraductal stagnation of pancreatic juice. These findings demonstrate that protein degradation in PPJ is accelerated by intraductal activation of serine proteases in the case of patients with CCP. 2-DE of PPJ from patients with CCP provides useful information for the evaluation of intraductal activation of zymogens and the progress of chronic pancreatitis.

Adult↗
PubMed1996

Regulation of ICAM-1 expression by inflammatory cytokines in rat mesangial cells.

We investigated the regulation of intercellular adhesion molecule 1 (ICAM-1) expression by the inflammatory cytokines interleukin 1 beta (IL-1), IL-6 and IL-8 in rat mesangial cells by enzyme-linked immunosorbent assay, flow cytometry and Northern blot analyses. ICAM-1 expression on mesangial cells was stimulated significantly by IL-1 beta, but not by IL-6 nor IL-8, in a dose-dependent manner. Levels of ICAM-1 mRNA were very low in unstimulated mesangial cells, while its expression was markedly induced by exposure to IL-1 beta for 3 h. IL-6 and IL-8 showed no effect on ICAM-1 mRNA accumulation. These results demonstrate that IL-1 beta, but not IL-6 nor IL-8, induces ICAM-1 mRNA and protein accumulation in rat mesangial cells.

Animals↗
PubMed1996

Large radiolucent tracheal foreign body found by CT scan caused dyspnea: an admonition on flexible fiberscopic foreign body removal.

A 25-year-old male patient with a sharp, large, and radiolucent tracheobronchial foreign body which was inhaled at the time of a traffic accident is reported on. CT scan was quite useful in finding this radiolucent foreign body. The patient had no respiratory disturbance because the foreign body was located in the level between bifurcation and left main bronchus; however, a flexible fiberscopic procedure performed to remove the body caused an airway obstruction and a dyspnea because the foreign body lodged in the subglottis. Remarkable progress has been made in the development of the flexible fiberscope system. Almost all medical facilities in Japan have flexible systems. However, the opportunities for young physicians to learn about rigid systems may now become limited. This case may warn us not to have too much confidence in the ability of flexible fiberscope system to remove this kind of large foreign body and remind us of the need to continue adequate training in the rigid systems.

Accidents, Traffic↗