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T Ikeda

Publications and source records attributed to T Ikeda.

At least 109 records · Page 6Linked to original sources
PubMed2001

Modulation by dietary restriction in gene expression related to insulin-like growth factor-1 in rat muscle.

Physiological adaptations induced by dietary restriction might include the modulation of the insulin-like growth factor 1 (IGF-1) axis. We investigated the effects of dietary restriction on aging-dependent changes in plasma level of IGF-1 and gene expression levels of type-1 IGF receptor (IGFR), insulin receptor substrate-1 (IRS-1), and IGF-1 in the diaphragm and quadriceps femoris muscle (QFM) of male F344 rats. The animals were fed ad libitum throughout life (AL), or provided with 70% of diet of AL rats from 6 weeks of age (DR). The plasma IGF-1 and steady-state levels of the genes were quantified by radioimmunoassay and the reverse transcription-polymerase chain reaction method, respectively. Immunohistochemical analysis in tissue sections was also performed for IGFR. Our results showed that dietary restriction: 1) decreased the plasma level of IGF-1; 2) increased the steady-state level of IGFR-mRNA at 6 and 16 months of age. and the peptide level at 6 months; 3) maintained IGF-1- and IRS-1-mRNA at a level similar to that in AL rats; and 4) delayed or inhibited an aging-dependent increase in IGFR-mRNA in the muscles. The present results suggest that dietary restriction could modulate IGF-1 signaling by augmenting local tissue response to IGF-1 and by maintaining the local production of the peptide, even though plasma IGF-1 is reduced.

Aging↗
PubMed2001

Effect of ionophores on in vitro excystment of Paragonimus ohirai metacercariae.

Ca2+ ionophores (A23187 and ionomycin) induced in vitro excystment of Paragonimus ohirai metacercariae, whereas Na+ ionophore (monensin) and K+ ionophores (nigericin and valinomycin) did not. The effect of A23187 on in vitro excystment was dependent on the concentration of the ionophore. A high concentration of 1 microM or more induced rapid excystment, but resulted in the death of metacercarial juveniles. The appropriate concentration of 0.2 microM induced in vitro excystment by 5 h after incubation with little or no damage to the juveniles.

Animals↗
PubMed2001

Assessment of the effect of revascularization early after CABG using ECG-gated perfusion single-photon emission tomography.

When an arterial graft is used, reversible perfusion defects on single-photon emission tomography (SPET) perfusion images are occasionally observed early after coronary artery bypass graft surgery (CABG), owing to the restricted flow capacity. The purpose of this study was to determine whether the functional information obtained with electrocardiography (ECG)-gated perfusion SPET could be helpful in evaluating the effect of revascularization early after CABG. Twenty-three patients (18 men and 5 women, mean age 65+/-9 years) underwent stress/re-injection thallium-201 ECG-gated SPET before and 4 weeks after CABG (13 with exercise and 10 with dipyridamole). Patency of all grafts was confirmed by coronary angiography 1 month after CABG. Cardiac functional data including the left ventricular ejection fraction (LVEF) and the transient ischaemic dilatation (TID) ratio were analysed using a commercially available automated program. The conventional stress and re-injection tomograms were interpreted by means of a five-point scoring system in a nine-segment model. Stress-induced reversible 201Tl perfusion defects were present in 64% of the myocardial segments bypassed by patent arterial grafts, in contrast to 42% of the myocardial segments bypassed by patent venous grafts (chi2=7.8, P=0.005). Of the 23 patients, 12 showed improvement in summed ischaemic scores (group 1), while 11 had no change or deterioration (group 2), although all grafts were patent on postoperative catheterization. The TID ratio improved in both group 1 and group 2 before and after CABG (1.14+/-0.13 vs 0.99+/-0.07, P=0.001 and 1.09+/-0.07 vs 0.94+/-0.05, P=0.002, respectively). However, LVEF did not significantly improve in group 1 or group 2 after CABG (42.5%+/-9.9% vs 47.5%+/-11.8%, and 52.1%+/-7.5% vs 53.1%+/-5.9%, respectively). Perfusion imaging or LVEF assessment is of limited value early after CABG. The TID ratio obtained with ECG-gated perfusion SPET may be a useful marker to evaluate the effect of revascularization early after surgery.

Aged↗
PubMed2001

Correlation between plasma endotoxin, plasma cytokines, and plasminogen activator inhibitor-1 activities in septic patients.

The objective of this study was to evaluate the relation between the clinical and plasma parameters and the changes in plasma endotoxin activity with 2 hours of endotoxin-adsorbing therapy using polymyxin B (PMX). A total of 88 consecutive patients were admitted for PMX treatment of severe sepsis or septic organ failure. Standard supportive care was continued without alteration during PMX treatment. Endotoxin, tumor necrosis factor-alpha (TNFalpha), interleukin-6 (IL-6), IL-10, and plasminogen activator inhibitor-1 (PAI-1) activities and clinical parameters were measured before, immediately after, and the day after PMX treatment. The mean APACHE II and III scores were 24.2 +/- 1.0 and 85.8 +/- 3.0, respectively. The 2-week survival rate was 51.1%. In survivors, TNFalpha, IL-6, IL-10, and PAI-1 activities were significantly decreased during the 2-hour PMX treatment, the following day, or both times. There was no significant change in the parameters, except for TNFalpha, after PMX in nonsurvivors. In the subgroup whose plasma endotoxin decreased more than 30%, IL-6, TNFalpha, and PAI-1 significantly decreased after 2 hours of PMX or the following day (or both), but all four parameters in nonsurvivors showed no significant change. Hence PMX adsorbed plasma endotoxins and contributed to reductions in plasma proinflammatory cytokine levels and to improved clinical parameters during the 2-hour treatment. Changes in these parameters correlated with changes in plasma endotoxin activity in survivors whose plasma endotoxin levels were adequately reduced.

APACHE↗
PubMed2001

Phase I/II and pharmacologic study of irinotecan and carboplatin for patients with lung cancer.

PURPOSE: To determine the maximum tolerated dose (MTD) of irinotecan combined with carboplatin, to evaluate its efficacy and toxicity for patients with lung cancer, and to examine its pharmacokinetics and pharmacodynamics. METHODS: The dose of irinotecan was escalated from 40 mg/m2 per week in increments of 10 mg/m2. Carboplatin was fixed at 300 mg/m2. Multivariate regression models with an interaction term were used to evaluate synergistic pharmacodynamic interactions. RESULTS: The MTD and recommended dose of irinotecan were 60 and 50 mg/m2, respectively. Dose-limiting toxicities were grade 4 neutropenia and grade 3 or 4 diarrhea. In phase II studies, response rates were 81.3% (95% confidence interval 61.8-100%) in 16 patients with small-cell lung cancer and 22.2% (2.7-41.8%) in 18 patients with non-small-cell lung cancer. Two patients (6%) experienced grade 4 neutropenia, thrombocytopenia, and grade 3 diarrhea. The area under the plasma concentration versus time curve (AUC) of carboplatin ranged from 2.87 to 9.31 mg x min/ml, with a median of 4.66 mg x min/ml. In pharmacodynamic analyses, the log-transformed surviving fraction in platelet count (SFp) showed a significant association with the AUC of carboplatin (P=0.010), while that in neutrophil count (SFn) was not significantly correlated with any pharmacokinetic parameter. The interaction term was not significant in either case. CONCLUSIONS: These results indicate that AUC-based dosing of carboplatin is still rational in combination chemotherapy. A more sensitive method for predicting life-threatening toxicities is needed, however, because traditional pharmacokinetic parameters were not adequate tools for identifying patients at high risk of severe neutropenia and diarrhea. This combination regimen has only modest activity, and further studies are necessary to evaluate a different dose schedule.

Adult↗
PubMed2001

Location of lesions in multiple evanescent white dot syndrome and the cause of the hypofluorescent spots observed by indocyanine green angiography.

PURPOSE: To determine the location of the lesions in the retina of a patient with multiple evanescent white dot syndrome (MEWDS) and to resolve the conflict in the cause of the hypofluorescent spots observed in the late phase of indocyanine green angiography (ICGA). CASE REPORT: A 27-year-old woman presented with a unilateral enlarged blind spot and a central scotoma. Fundus examination of the left eye showed many round, indistinctly circumscribed white dots extending from the posterior pole toward the periphery. Fluorescein angiography demonstrated hyperfluorescence due to staining at the location of the white dots. Staining was also observed on the venous wall which was consistent with periphlebitis. The location of the scotomas corresponded with the hypofluorescent spots observed around the optic disc and in the macula in the late phase of ICGA. The scotomas disappeared with the resolution of the hypofluorescent spots, and the sites of other hypofluorescent spots were in accord with the sites of periphlebitis. Visual evoked cortical potentials disclosed no laterality, and the critical fusion frequency was reduced but normalized with the disappearance of the scotoma. CONCLUSION: The initial lesions of MEWDS occur in the retinal pigment epithelium and photoreceptor cells, but when MEWDS is complicated by periphlebitis, the inflammatory lesions extend to the inner layers of the retina. The inflammatory changes involve the choroid and all layers of the retina, which then block the weak background fluorescence in the later phase of ICGA and cause the hypofluorescent spots. The visual field defects are probably caused by retinal dysfunction due to the inflammatory changes.

Adult↗
PubMed2001

Changes in atrial natriuretic peptide and brain natriuretic peptide associated with hypobaric hypoxia-induced pulmonary hypertension in rats.

Experimental pulmonary hypertension induced in a hypobaric hypoxic environment (HHE) is characterized by structural remodeling of the heart and pulmonary arteries. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) both have diuretic, natriuretic, and hypotensive effects, and both are involved in cardiovascular homeostasis as cardiac hormones. To study the effects of HHE on the natriuretic peptide synthesis system, 170 male Wistar rats were housed in a chamber at the equivalent of the 5500-m altitude level for 1-12 weeks. After 1 week of HHE, pulmonary arterial pressure was significantly raised, and the ratio of left ventricle plus septum over right ventricle of the heart showed a significant decrease (compared with those of ground-level control rats). In both ventricular tissues, the expression of ANP messenger (m)RNA and BNP mRNA increased after exposure to HHE. The amounts of ANP and BNP had decreased significantly in right atrial tissue at 12 weeks of HHE (compared with those of the controls), whereas in ventricular tissues at the same time point, both levels had increased significantly. In in situ hybridization and immunohistochemical studies, the staining of the mRNAs for ANP and BNP and of ANP and BNP themselves was more intense in both ventricular tissues after exposure to HHE than before (i.e., in the controls). The results suggest that, in response to HHE, the changes in ventricular synthesis are similar for ANP and BNP. These changes may play a role in modulating pulmonary hypertension in HHE. However, under our conditions, pulmonary hypertension increased progressively throughout the HHE period.

Altitude Sickness↗
PubMed2001

Local infusion of nerve growth factor attenuates myelinated nerve fiber sprouting into lamina II of the spinal dorsal horn and reduces the increased responsiveness to mechanical stimuli in rats with chronic constriction nerve injury.

PURPOSE: To clarify the relationship between allodynia and the sprouting of myelinated fibers, we examined whether the administration of nerve growth factor (NGF) affected the paw withdrawal response to non-noxious mechanical stimuli and the sprouting of myelinated fibers into lamina II of the spinal dorsal horn, using a chronic constriction injury model of the sciatic nerve. METHODS: Mechanical allodynia was determined as the threshold of the withdrawal response stimulated by von Frey filaments. Sprouting was examined using horseradish peroxidase conjugated to the B fragment of cholera toxin (B-HRP). NGF was continuously infused into the site of nerve injury for 14 days after nerve ligation. RESULTS: With vehicle infusion, significantly increased responsiveness to mechanical stimuli was observed on postoperative days (PODs) 5, 7, and 14 after ligation, compared with before surgery, and B-HRP-positive fibers were newly localized in lamina II on PODs 7 and 14. Infusion of NGF reduced the responsiveness to mechanical stimuli on 5, 7, and 14 PODs and B-HRP-positive fibers in lamina II on PODs 7 and 14. CONCLUSION: We propose that the suppression of the increased responsiveness to mechanical stimuli produced by NGF could be related to the disappearance of B-HRP-positive fibers in lamina II.

Journal Article↗
PubMed2001

Cationic polymer-mediated genetic transduction into cultured human chondrosarcoma-derived HCS-2/8 cells.

The usefulness of three types of cationic polymer, i.e., degraded polyamidoamine (PAMAM) dendrimer (SuperFect Transfection Reagent; Oiagen), linear polyethylenimine (PEI; ExGen 500; Euromedex), and branched PEI in gene delivery into chondrocytes was examined comparatively. A plasmid vector containing the Escherichia coli LacZ (pSES.beta) was combined with one of the three cationic polymers at various molar ratios and the resultant complex (polyplex) was used to transduce a human chondrocyte-like cell line, HCS-2/8. Gene expression was evaluated by an O-nitrophenyl beta-D-galactopyranoside (ONPG) assay and by staining with 0.05% 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-gal; Nacalai Tesque). The ONPG assay showed that the highest delivery rate was achieved when 2microg of pSES.beta was combined with either 21 microg of dendrimer, 1.7microg of linear PEI, or 2.0microg of branched PEI. At the same DNA/polymer ratios, the proportions of X-gal-stained cells were also the highest (31.3 +/- 7.5%, 30.3 +/- 9.0%, and 8.3 +/- 3.1%, respectively). LacZ expression reached the highest level 3 days after the dendrimer-mediated transduction, and gradually declined, returning to the background level on day 14. Possible cytotoxicity was examined by trypan blue staining and phase contrast microscopic observations. Neither cytotoxicity nor morphological change was induced at the optimal dose of each polymer. The cationic polymers, particularly the degraded dendrimer and linear PEI, would be a useful nonviral vector for gene delivery to cells of chondrocytes.

Bone Neoplasms↗
PubMed2001

Identification of sequence polymorphisms in two sulfation-related genes, PAPSS2 and SLC26A2, and an association analysis with knee osteoarthritis.

Osteoarthritis (OA) is one of the most common musculoskeletal disorders and is characterized by degeneration of articular cartilage. Sulfation of extracellular matrix proteins in articular cartilage is an important step in maintaining normal cartilage metabolism. Two sulfation-related genes have been reported as the causal genes of severe chondrodysplasias: mutations in PAPSS2 (3'-phosphoadenosine 5'-phosphosulfate synthase 2) cause spondylo-epimetaphyseal dysplasia (SEMD), and mutations in SLC26A2 (solute carrier family 26, member 2) cause diastrophic dysplasia. Given their critical roles in cartilage metabolism and the severe phenotypes that result from mutations in these genes, we examined PAPSS2 and SLC26A2 as candidate susceptibility loci for OA. We identified sequence polymorphisms in the coding and core promoter regions of these genes and analyzed their potential association with knee OA within the Japanese population. Ten sequence polymorphisms were detected in PAPSS2 and five in SLC26A2. An association analysis showed suggestive association of one minor polymorphism in the promoter region of SLC26A2. This 4-bp adenine deletion allele, del4A, was over-represented in knee OA (P = 0.043, odds ratio = 3.43) and is thought to confer a minor susceptibility to knee OA within the Japanese population. Haplotype analysis showed no evidence of association with the two genes, however, excluding them as major susceptibility loci for knee OA.

Anion Transport Proteins↗
PubMed2001

Identification of sequence polymorphisms of the COMP (cartilage oligomeric matrix protein) gene and association study in osteoarthrosis of the knee and hip joints.

Osteoarthrosis (OA) is a common cause of musculoskeletal disability characterized by late-onset degeneration of articular cartilage. Although several candidate genes have been reported, susceptibility genes for OA remain to be determined. Hereditary osteochondral dysplasias produce severe, early-onset OA and hence are models for common idiopathic OA. Among them are pseudoachondroplasia and multiple epiphyseal dysplasia, both of which are caused by mutations in the cartilage oligomeric matrix protein (COMP) gene. Therefore, COMP may be a susceptibility gene for OA. We screened for polymorphisms by direct sequencing of all exons of the COMP gene with their flanking intron sequences and the promoter region. We identified 16 polymorphisms, of which 12 were novel. Using six polymorphisms spanning the entire COMP gene, we examined the association of COMP in Japanese patients with OA of the knee and hip joints. Genotype and allele frequencies of the polymorphisms were not significantly different between OA and control groups, and there was no significant difference in haplotypes. These results do not support an association between COMP and OA in the Japanese population.

Cartilage↗
PubMed2001

Paraoxonase gene polymorphisms and plasma oxidized low-density lipoprotein level as possible risk factors for exudative age-related macular degeneration.

PURPOSE: Paraoxonase (E.C.3.1.1.2) is a polymorphic protein shown to prevent low-density lipoprotein oxidation. Our purpose is to evaluate the hypothesis that paraoxonase gene polymorphisms and plasma oxidized low-density lipoprotein level play a role in the occurrence of exudative age-related macular degeneration. METHODS: We analyzed paraoxonase genotypes (A/B, Gln-Arg192 and L/M, Leu-Met54) and plasma oxidized low-density lipoprotein levels in 72 unrelated Japanese patients with exudative age-related macular degeneration and compared the results with those of 140 age-matched and sex-matched control subjects. RESULTS: The distribution of paraoxonase 192 and paraoxonase 54 polymorphisms was significantly different between the patients with age-related macular degeneration and control subjects (chi-square = 6.226, P =.0445, and chi-square = 6.863, P =.0323, respectively). The high frequency of the BB genotype at position 192 was observed in the exudative age-related macular degeneration group compared with control subjects (52.8% vs 35.0%, respectively; P =.0127). The high frequency of the LL genotype at position 54 was observed in the patients more than the controls (91.7% vs 77.1%, respectively; P =.0090). The mean (+/- SE) oxidized low-density lipoprotein levels in the patients was significantly higher than in the controls (19.1 +/- 1.0 vs 16.2 +/- 0.6 U/ml, P <.01). CONCLUSION: These results indicate that the paraoxonase gene polymorphisms may represent a possible genetic risk factor for age-related macular degeneration and that increased plasma oxidized low-density lipoprotein may be involved in the pathogenesis of age-related macular degeneration.

Aged↗
PubMed2001

Down regulation of the tumor suppressor gene maspin in breast carcinoma is associated with a higher risk of distant metastasis.

BACKGROUND: Maspin (mammary serpin) is a relatively novel serine protease inhibitor with tumor suppressing function in breast cancer. Maspin expression was found in normal breast epithelial cells, but was decreased during tumor progression. Only a few systematic analyses of this phenomenon have been undertaken so far. In this study we developed specific nested reverse transcription polymerase chain reaction (RT-PCR) conditions for the detection of maspin expression in human breast carcinoma and assessed maspin's association with the clinical behavior of primary breast cancers. METHODS: Tumor specimens obtained from 45 primary breast cancer patients were analyzed for maspin expression by a nested RT-PCR assay. Recurrence free survival was evaluated and correlated to maspin expression. RESULTS: The maspin transcript was detected in 29 (64%) breast cancer specimens whereas no expression was found in 16 (36%) cancer specimens. This expression was unrelated to any of the established prognostic factors. However, 6 out of 8 patients who developed distant metastasis (lymph nodes, lung, liver, bone, pleura) within 3 yr after their initial diagnosis showed no maspin expression of the primary breast cancer (p < 0.05). CONCLUSIONS: The lack of maspin expression in breast cancer seems to be associated with a short disease free survival and supports maspin's function as an indicator of tumor aggressiveness and metastatic potential. Nested RT-PCR is a sensitive method to determine maspin expression in human breast cancer tissue.

Adult↗
PubMed2001

Investigation of Corneal Autofluorescence in Diabetic Patients.

Purpose: The investigation of corneal autofluorescence in diabetic patients.Objects and Methods: Corneal autofluorescence was investigated with a newly-developed fluorophotometer (wave length: excitation, 290-390 nm; emission, 430-630 nm) having, fluorescence characteristics involving those of reduced pyridine nucleotides (PN) and advanced glycation endoproduct (AGE) except pentosidine and pyrraline. Twenty-eight patients with non-insulin-dependent diabetes mellitus and sixty-seven healthy volunteers were studied.Results: The corneal autofluorescence was 1.65 times higher than that of controls (P <.0001). In non-insulin-dependent diabetes mellitus, the corneal autofluorescenece was not correlated significantly with various diabetic parameters in blood (r < 0.4). In controls, the corneal autofluorescence was correlated significantly with age (r = 0.438).Conclusion: The corneal autofluorescence has some relation with PN and AGE accumulation in the cornea.

Journal Article↗
PubMed2001

VCAM-1 expression precedes macrophage infiltration into subendothelium of vein grafts interposed into carotid arteries in hypercholesterolemic rabbits--a potential role in vein graft atherosclerosis.

Intimal hyperplasia and atherosclerosis are major causes of late vein graft failure after coronary artery bypass surgery. Hypercholesterolemia appears to be a key risk factor for atherosclerosis in vein grafts as well as in native arteries. We used a rabbit model of interposition jugular vein graft to the carotid artery and compared intimal thickening, macrophage accumulation, and VCAM-1 expression between hypercholesterolemic (H group) and normocholesterolemic (N group) rabbits. Fifty-nine rabbits were divided into H and N groups. Intimal thickening in vein grafts was approximately three times more prominent in the H group than in the N group. Macrophage accumulation progressively increased with time in H group vein grafts, although it was negligible in the N group. In the H group, moreover, macrophages were initially more abundant in deep intima, and subsequently accumulated in subendothelium of the grafted vein. VCAM-1 expression in luminal endothelial cells of the grafted veins was time-dependently increased after the vein graft surgery in both the H and N groups, and was more prominent in the H group. Comparison of the time-courses between macrophage accumulation and VCAM-1 expression revealed that VCAM-1 expression in luminal endothelium preceded subendothelial accumulation of macrophages. VCAM-1 expression and macrophage accumulation may be key factors which regulate progression of vein graft atherosclerosis.

Animals↗
PubMed2001

Withanolide-type steroids from Solanum cilistum.

Six withanolide-type steroids, named as cilistols a, b, d, q, g and f, respectively, were isolated from the leaves of Solanum cilistum. The major component among them, cilistol a, was characterized as (22R, 24S, 25R, 26R)-1-oxo-22, 26; 24, 25-diepoxy-17alpha, 26-dihydroxyergost-2,5-diene on the basis of spectroscopic properties and X-ray crystallographic analysis; the other isolated compounds had closely related structures. This is the first report of withanolide-type steroids in the Solanum genera.

Ergosterol↗
PubMed2001

Effects of previous noxious stimulus applied to remote areas on noxious stimulus-evoked c-Fos expression in the rat trigeminal nucleus caudalis.

Noxious stimulus-evoked c-Fos expression in the spinal dorsal horn is modulated by noxious stimuli applied previously to remote areas of the body. To confirm the existence of such modulation in c-Fos expression in the trigeminal system, changes in c-Fos expression in the trigeminal nucleus caudalis induced by formalin injection into the rat whisker pad were examined by previously injecting formalin into different areas (contralateral whisker pad, ipsilateral or contralateral forepaw) of the body. Formalin injection-evoked c-Fos expression in this nucleus was significantly reduced by previous formalin injection into the contralateral whisker pad or ipsilateral forepaw but not into the contralateral forepaw. The interval between the two injections of formalin that produced a maximal reduction of formalin injection-evoked c-Fos expression was 1 h, and the reduction of c-Fos expression was less when the interval of the two noxious stimuli was longer or shorter than 1 h. These results suggested that noxious stimulus-evoked c-Fos expression in the trigeminal nucleus caudalis is reduced by noxious stimulus applied previously to remote areas, and the reduction is dependent on the area of previous noxious stimulation and interval between the two noxious stimuli.

Animals↗