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Biomedical subjects

Y Okuda

Publications and source records attributed to Y Okuda.

At least 37 records · Page 2Linked to original sources
PubMed2001

Elevated levels of vascular endothelial growth factor in the sera of patients with rheumatoid arthritis correlation with disease activity.

To evaluate vascular endothelial growth factor (VEGF) levels in relation to disease activity in rheumatoid arthritis (RA), VEGF in the serum of 155 patients with RA and 75 healthy control subjects was quantified by our highly sensitive enzyme-linked immunosorbent assay. VEGF levels were found to correlate with the articular index (AI) and Lansbury's activity index (LI). Patients with RA had a mean serum VEGF concentration of 153.5+/-111.8 pg/ml, which was significantly higher than control subjects (104.8+/-65.7 pg/ml; P<0.01). VEGF concentration was elevated significantly according to disease progression as expressed by stages I to IV and correlated with AI (r=0.530, P<0.0001) and LI (r=0.688, P<0.0001) in stages I and II as well as with the conventional erythrocyte sedimentation rate or serum C-reactive protein concentration. Serum VEGF levels may therefore be valuable as a marker of disease activity in patients with early RA, and this cytokine may play a significant role in the pathophysiology of RA.

Arthritis, Rheumatoid↗
PubMed2001

Hyperglycemia in diabetic rats reduces the glutathione content in the aortic tissue.

The glutathione redox cycle plays a major role in scavenging hydrogen peroxide (H2O2) under physiological conditions. Recently, we demonstrated that a high glucose concentration in the culture medium reduced the level of H2O2 scavenging activity of human vascular smooth muscle cells (hVSMCs). We also showed that a high glucose concentration reduced the intracellular glutathione (GSH) content and the rate of uptake of cystine, which itself is a rate-limiting factor that maintains the GSH level (FEBS Lett.421: 19-22,1998). In the present study, we investigated whether the hyperglycemic condition in diabetic rats impairs the glutathione content in the aortic tissue in vivo. Wistar rats were divided into the following three groups: streptozotocin-induced diabetic rats (STZ-D, n=7), insulin-treated STZ-D rats (I-STZ-D, n=8), and non-diabetic controls (C, n=7). Fourteen days after streptozotocin injection, the aortic tissue was extracted and the GSH content in the aortic tissue was measured. Furthermore, the relationship between the GSH content in the aortic tissue and blood glucose level in Otsuka Long-Evans Tokushima Fatty (OLETF) rats aged 30 weeks, which developed diabetes spontaneously, was investigated. The GSH content in the aortic tissue of the STZ-D group (0.99+/-0.14 nmol/mg protein) was significantly lower than that of the control group (1.68+/-0.15 nmol/mg protein). Insulin treatment to the diabetic rats restored the GSH content in the aortic tissue (I-STZ-D group; 1.45+/-0.11 nmol/mg protein). Among the 22 Wistar rats, the GSH content in the aortic tissue was negatively correlated with the blood glucose level (r=-0.69, p<0.01, n=22). Among the OLETF rats, a similar negative correlation between the GSH content in the aortic tissue and blood glucose level was seen (r=-0.64, p<0.05, n=10). We demonstrated in vivo that the hyperglycemic condition in STZ-induced diabetic Wistar rats and OLETF rats reduced the GSH content in aortic tissue. This suggested reduced glutathione redox cycle function of aorta.

Animals↗
PubMed2001

Insulin up-regulates tumor necrosis factor-alpha production in macrophages through an extracellular-regulated kinase-dependent pathway.

Hyperinsulinemia has recently been reported as a risk factor for atherosclerotic diseases such as coronary heart disease; however, the effect of insulin on the development of atherosclerosis is not well understood. Here we have investigated the direct effect of insulin on macrophages, which are known to be important in the atherosclerotic process. We treated THP-1 macrophages with insulin (10(-7) m) and examined the gene expression using nucleic acid array systems. The results of array analysis showed that insulin stimulated gene expression of tumor necrosis factor-alpha (TNF-alpha) the most among all genes in the analysis. In addition, insulin administration to macrophages enhanced both mRNA expression and protein secretion of TNF-alpha in a dose-dependent manner. To determine the signaling pathway involved in this TNF-alpha response to insulin, we pretreated the cells with three distinct protein kinase inhibitors: wortmannin, PD98059, and SB203580. Only PD98059, which inhibits extracellular signal-regulated kinases, suppressed insulin-induced production of TNF-alpha mRNA and protein in THP-1 macrophages. These observations indicate that insulin stimulates TNF-alpha production in macrophages by regulating the expression of TNF-alpha mRNA and that the extracellular signal-regulated kinase signaling pathway may have a critical role in stimulating the production of TNF-alpha in response to insulin in macrophages.

Cell Line↗
PubMed2001

T cell receptor dynamism of mucosal and systemic CD4+ T cells in the course of an immune response to Escherichia coli heat-labile enterotoxin.

The changes in T cell receptor (TCR) Vbeta expression, use, and clonality in mice orally challenged with Escherichia coli heat-labile enterotoxin (LT) were assessed. Use of the TCR Vbeta family and clonality were significantly changed at the single-cell level. In Peyer's patches of treated mice, use of TCR Vbeta6, Vbeta8, and Vbeta14 increased in CD4(+)CD44(+) T cells, compared with use in nontreated mice. On the other hand, use of TCR Vbeta1 and Vbeta8 was enhanced in splenic CD4(+)CD44(+) T cells. Intraepithelial lymphocytes isolated from LT-challenged mice showed expanded clonality (e.g., Vbeta1, Vbeta2, Vbeta9, and Vbeta18) and altered TCR Vbeta use (e.g., Vbeta15, Vbeta16, and Vbeta17). These findings reveal that oral administration of LT has distinct effects on mucosal versus systemic alphabeta T cells for induction of CD4(+) T cells with selected Vbeta use. This most likely reflects the function of LT as a mucosal modulator.

Administration, Oral↗
PubMed2001

Expression and characterization of a magnetosome-associated protein, TPR-containing MAM22, in Escherichia coli.

A magnetosome-associated protein, MAM22, contains a TPR domain (five TPR motifs and one putative TPR motif) that has been known to mediate protein-protein interactions. We expressed the mam22 gene in Escherichia coli and found that the purified MAM22 was reversibly self-aggregated by NaCl. The structural model of MAM22 which has been proposed on the basis of the crystal structure of the N-terminal TPR domain of a human Ser/Thr protein phosphatase suggests the novel hydrophobic colloidal features of MAM22 with TPR motifs.

Amino Acid Motifs↗
PubMed2001

Neutralization of vascular endothelial growth factor prevents collagen-induced arthritis and ameliorates established disease in mice.

Vascular endothelial growth factor (VEGF) is implicated in the pathogenesis of inflammatory joint diseases, including rheumatoid arthritis (RA). To determine the importance of this cytokine in vivo, the effect of administering VEGF-neutralizing antibodies to mice with collagen-induced arthritis (CIA), which has many immunological and pathological similarities to human RA, has been investigated. Either saline, normal rabbit immunoglobulin or anti-human VEGF121 rabbit polyclonal antibody was administered to mice subcutaneously either before the onset of arthritis or after the establishment of clinical disease. Anti-VEGF antibody administered prior to disease onset significantly delayed the development of arthritis and decreased clinical score and paw thickness as well as histological severity. On the other hand, the frequency of occurrence of disease compared to either the control group administered saline or normal rabbit immunoglobulin was not altered. Anti-VEGF antibody also significantly ameliorated clinical and histological parameters even when administered after disease onset. These results indicate a possible therapeutical potential for anti-VEGF treatment in human arthritis.

Animals↗
PubMed2001

Enhancement of T helper2 response in the absence of interleukin (IL-)6; an inhibition of IL-4-mediated T helper2 cell differentiation by IL-6.

Functional roles of interleukin (IL-)6 in T cell response were investigated. Mice deficient in IL-6 and wild mice were immunized with antigens (myelin oligodendrocyte glycoprotein or methylated BSA) and production of IL-4 and interferon (IFN)-gamma by regional lymph nodes was measured. IL-6 deficiency led to an enhancement of IL-4 and an inhibition of IFN-gamma production. Moreover, polyclonal stimulation of spleen T cells from unimmunized IL-6-deficient mice with anti-CD3 plus anti-CD28 antibodies (Abs) demonstrated an enhancement of T helper (Th)(2)responses. The presence of IL-6, however, augmented IL-4 production but it inhibited IFN-gamma expression by spleen T cells in response to polyclonal stimulation and by antigen-primed spleen T cells in response to re-challenge with the antigen. In contrast, the induction of spleen CD4-positive T cells into Th(2)cells in vitro by the anti-CD3 plus IL-4 was completely suppressed by exogenously added IL-6, whereas Th(1)differentiation of T cells by the anti-CD3 plus IL-12 was not inhibited by the presence of IL-6. Thus, these results indicate that IL-6 physiologically could modulate qualitative T cell response and suggest that it augments Th(1)responses partly through its inhibitory capability of IL-4-induced Th(2)differentiation of naive T cells.

Adjuvants, Immunologic↗
PubMed2001

Osmolality dependence of erythrocyte sedimentation and aggregation in a strong magnetic field.

In order to specify the major determinant of the magnetic enhancement of erythrocyte sedimentation observed previously, the dependence of erythrocyte sedimentation rate (ESR) on osmolality was measured under a strong magnetic field. Even at hypotonic osmolality, an increase in ESR due to aggregation was observed in plasma solution as compared with that without aggregation in saline solution. However, the magnetic field did not enhance ESR at hypotonic osmolality, when the cell shape was an isotropic sphere (spherocyte). Thus, we narrowed our search to a mechanism that would explain the enhanced ESR found specifically in anisotropic erythrocytes. It was concluded that the major determinant can only work for anisotropic erythrocytes and is a magnetic field-induced increase in an intermembrane adhesive area due to magnetic orientation of anisotropic erythrocytes.

Adult↗
PubMed2001

High concentration sevoflurane induction of anesthesia accelerates onset of vecuronium neuromuscular blockade.

PURPOSE: To investigate neuromuscular block using accelography after administration of vecuronium under sevoflurane 8% induction and maintenance with sevoflurane 2% in adults. METHODS: Patients were allocated to three groups: (1) group I: anesthesia was induced and maintained with propofol and fentanyl (n= 15), (2) group II: anesthesia was induced with propofol and maintained with N2O(66%)-O2-sevoflurane 2% (n = 15), (3) group III: anesthesia was induced with sevoflurane 8% using a vital capacity inhalation induction and maintained with N2O(66%)-O2-sevoflurane 2% (n = 15). 0.1 mg x kg(-1) vecuronium was used for paralysis three minutes after anesthetic induction and reversed using intravenous 0.04 mg x kg(-1) neostigmine with 0.02 mg kg atropine when the train-of-four (TOF) ratio returned to 25%. RESULTS: The onset time from initial administration of vecuronium to maximal block in the group III was shorter than that in the groups I and II (139 +/- 35, 193 +/- 35 and 188 +/- 47s, respectively: P < 0.05). The clinical duration from maximal block to 25% recovery of TOF ratio in group II and III was longer than that in the group I (47 +/- 15, 48 +/- 14 and 36 +/- 10 min, respectively: P < 0.05). The reversal times from administration of neostigmine to 75% of TOF ratio in groups II and III were longer than that in the group I (196 +/- 53, 208 +/- 64 and 136 +/- 28s, respectively: P < 0.05). CONCLUSIONS: Vital capacity inhalation induction of anesthesia with sevoflurane accelerates onset and prolongs duration of vecuronium neuromuscular block compared with propofol-fentanyl anesthesia.

Adjuvants, Anesthesia↗
PubMed2001

Acute effects of growth hormone on metabolism of pancreatic hormones, glucose and ketone bodies.

Controversy exists as to whether acute administration of growth hormone has insulin-like effects. In conscious dogs, acute effects on plasma flows, plasma glucose, hepatic glucose output, free fatty acids, ketone bodies, insulin, and glucagon were determined following intravenous injection of 1 mg of growth hormone extracted from the canine pituitary gland. The following results were obtained: (1) Plasma flows in the portal vein, hepatic artery and hepatic vein were significantly increased 20 min after growth hormone administration. (2) By 40 min after growth hormone, the glucose concentration in these three vessels was significantly increased. (3) Hepatic glucose output was significantly increased 60 min after growth hormone administration. (4) Free fatty acids levels were significantly but transiently increased at 20 min, while ketone body concentrations were elevated at 120-180 min. (5) The insulin levels in the three vessels demonstrated a biphasic response. In the portal vein, they were significantly higher 20 min after growth hormone and again at 150-180 min. Glucagon concentrations were increased in all three vessels by 20 min and remained elevated for the remainder of the experiment. These results do not support an acute insulin-like action of growth hormone in normal dogs.

Animals↗
PubMed2001

Pediatric caudal block with mepivacaine, bupivacaine or a mixture of both drugs: requirement for postoperative analgesia and plasma concentration of local anesthetics.

STUDY OBJECTIVES: To assess the effects of pediatric caudal block using mepivacaine, bupivacaine, or a mixture of both drugs on postoperative analgesia, and to examine plasma concentrations of the local anesthetics after caudal injection. DESIGN: Prospective, randomized, double-blind study. SETTING: Operating room and pediatric surgical ward. PATIENTS: 60 ASA physical status I children weighing 10 to 20 kg (26 females, 34 males), and scheduled for inguinal herniorrhaphy. INTERVENTIONS: Patients randomly received caudal block with 1 mL/kg of mepivacaine 1% (Group M, n = 20), 1 mL/kg of bupivacaine 0.25% (Group B, n = 20), or a mixture of 0.5 mL/kg of mepivacaine 1% and 0.5 mL/kg of bupivacaine 0.25% (Group MB, n = 20) after induction of anesthesia with sevoflurane in 50% oxygen (O2). Anesthesia was maintained with 66% nitrous oxide in O2 supplemented with sevoflurane at an end-tidal concentration of less than 1%. MEASUREMENTS AND MAIN RESULTS: Postoperative pain scores using a pediatric pain scale and plasma concentration of each local anesthetic were measured. In Group M, four patients required postoperative analgesics within the first 24 hours. However, no patients required postoperative analgesics in Groups B and MB. In Group M, the plasma concentration of mepivacaine of two patients exceeded 5 microg/kg of the level of toxicity. However, these patients did not show any toxic symptoms. Because a mixture of two local anesthetics halves the concentration of each local anesthetic, the plasma concentrations of mepivacaine and bupivacaine in Group MB were significantly lower than those of Groups M and B. CONCLUSIONS: Pediatric caudal block with a mixture of mepivacaine and bupivacaine is effective for intraoperative and postoperative analgesia.

Age Factors↗
PubMed2001

Sudden unconsciousness during a lesser occipital nerve block in a patient with the occipital bone defect.

Occipital nerve block is usually considered to be a very simple and safe regional anaesthetic technique. We describe a case of sudden unconsciousness during a lesser occipital nerve block in a patient with an occipital bone defect. A 63-year-old man complained of headache, which was localized to the right occipital region. A right lesser occipital nerve block with a local anaesthetic was performed for treatment. During the lesser occipital nerve block, the patient suddenly became disturbed and lost consciousness. Two hours after the incident, the patient was fully awake without neurological sequelae. He had previously undergone a microvascular decompression for right trigeminal neuralgia. The patient had a bone defect following craniotomy. We believed that the loss of consciousness during lesser nerve block may be due to a subarachnoid injection. Occipital nerve block is relatively contraindicated in the presence of a bone defect.

Anesthetics, Local↗
PubMed2001

Analysis of Pfmdr 1 gene in mefloquine-resistant Plasmodium falciparum.

Drug resistance in Plasmodium falciparum is a serious problem in most endemic areas. Recent studies have suggested the potential involvement of genes in the MDR gene family in resistance to quinoline-containing compounds in P. falciparum. In our present studies, a molecular analysis of pfmdr 1 in isolate strain of P. falciparum, 523a R, from Japanese mefloquine-resistant patient was done to determine the reported association of pfmdr 1 intragenic alleles and mefloquine resistance, and to examine the antimalarial activities of several antimalarial agents against the P. falciparum strain. The antimalarial activities against the strain was decreased susceptibility to mefloquine, artemisinin and halofantrine, in contrast increased susceptibility to chloroquine. The DNA sequence analysis of pfmdr 1 gene in a strain reveled no association of intragenic alleles with mefloquine resistance. Furthermore, the overexpression of pfmdr1 mRNA have been observed and it is about 7.2 times higher than sensitive strain. Our data shows that overexpression of pfmdr1 gene may be associated in mefloquine-resistance mechanism.

ATP-Binding Cassette Transporters↗
PubMed2001

Clinical evaluation of anti-tuberculous glycolipid immunoglobulin G antibody assay for rapid serodiagnosis of pulmonary tuberculosis.

Previously we reported the development of a highly sensitive enzyme-linked immunosorbent assay specific for anti-tuberculous glycolipid (anti-TBGL) for the rapid serodiagnosis of tuberculosis. In this study, the usefulness of an anti-TBGL antibody assay kit for rapid serodiagnosis was evaluated in a controlled multicenter study. Antibody titers in sera from 318 patients with active pulmonary tuberculosis (216 positive for Mycobacterium tuberculosis in smear and/or culture tests and 102 smear and culture negative and clinically diagnosed), 58 patients with old tuberculosis, 177 patients with other respiratory diseases, 156 patients with nonrespiratory diseases, and 454 healthy subjects were examined. Sera from 256 younger healthy subjects from among the 454 healthy subjects were examined as a control. When the cutoff point of anti-TBGL antibody titer was determined as 2.0 U/ml, the sensitivity for active tuberculosis patients was 81.1% and the specificity was 95.7%. Sensitivity in patients with smear-negative and culture-negative active pulmonary tuberculosis was 73.5%. Even in patients with noncavitary minimally advanced lesions, the positivity rate (60.0%) and the antibody titer (4.6 +/- 9.4 U/ml) were significantly higher than those in the healthy group. These results indicate that this assay using anti-TBGL antibody is useful for the rapid serodiagnosis of active pulmonary tuberculosis.

Antibodies, Bacterial↗