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Biomedical subjects

Y Ueki

Publications and source records attributed to Y Ueki.

At least 37 records · Page 2Linked to original sources
PubMed2000

Induction of COX-2 expression by nitric oxide in rheumatoid synovial cells.

Prostaglandins formed by cyclooxygenase (COX) enzymes are important mediators of inflammation. The contribution of inducible COX-2 in the rheumatoid synovium is well documented. In this study, we evaluated the contribution of nitric oxide (NO) to COX-2 expression in rheumatoid synovial cells. Exposure of rheumatoid synovial cells to a NO donor, SNAP, induced COX-2 protein expression in a dose-dependent manner. RT-PCR analysis also demonstrated that COX-2 mRNA was induced in SNAP-treated synovial cells. Dexamethasone at therapeutic concentrations markedly inhibited this NO-mediated COX-2 expression in synovial cells. In contrast to its effect on COX-2 expression, SNAP did not affect the constitutive expression of COX-1 in rheumatoid synovial cells. Our findings suggest that NO is an important modulator of COX-2 expression and that glucocorticoids exert their anti-inflammatory action in rheumatoid synovium, at least in part, by suppression of COX-2 induction.

Arthritis, Rheumatoid↗
PubMed2000

X-ray fluorescence analysis of trace metal ions following a preconcentration of metal-diethyldithiocarbamate complexes by homogeneous liquid-liquid extraction.

A homogeneous liquid-liquid extraction method for 36 metal ions with diethyldithiocarbamate was studied. As a result, 11 metal ions were extracted as metal-chelates. Under the experimental conditions, the maximum concentration factor was 500 (i.e., 0.1 mL of sedimented liquid phase was produced from 50 mL of aqueous phase). Moreover, the proposed method was utilized as a preconcentration method for X-ray fluorescence analysis of these metals. The recovery of each metal was ca. 97-100%. All calibration curves were linear over the range of 5.0 x 10(-7) mol L-1 to 1.0 x 10(-5) mol L-1. The detection limits were at the 10(-8) mol L-1 levels and the relative standard deviations were below 5% (5 determinations). When the proposed method was used for the determination of contaminants in a synthetic sample (Al-based alloy model) and of components in an Au-Pd alloy, the results were satisfactory.

Journal Article↗
PubMed2000

High serum concentrations of soluble E-selectin in patients with impaired glucose tolerance with hyperinsulinemia.

High serum concentrations of soluble adhesion molecules are present in diabetics, but whether similar levels are present in patients with impaired glucose tolerance (IGT) is unclear. We measured serum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), and sE-selectin in 128 nondiabetic Japanese subjects. The concentrations of sICAM-1, sVCAM-1, and sE-selectin in IGT patients (n=47) were not different from those in subjects with normal glucose tolerance (NGT; n=81). IGT patients were subdivided into two groups by the results of 75 g OGTT, those with low- (hypoinsulinemia; n=23) or high-insulin (hyperinsulinemia; n=24). The levels of sICAM-1 and sVCAM-1 were not different among NGT and IGT with high-insulin or with low-insulin. However, sE-selectin concentrations were significantly higher in IGT patients with high-insulin than in NGT and IGT with low-insulin (61.1+/-3.4, 47.1+/-1.8 and 43.7+/-3.9 ng/ml, respectively, P<0.001). Adjustment for age and gender did not influence the results. Serum sE-selectin concentrations correlated significantly with the area under the curve of insulin (AUC(insulin)), AUC(glucose), diastolic blood pressure, and triglyceride levels (r=0.35, 0.26, 0.18 and 0.21, respectively), and negatively with HDL-cholesterol levels (r=-0.20). Multiple regression analysis showed that AUC(insulin) was the only independent factor that correlated with sE-selectin levels (P<0.001). Our results indicate that hyperinsulinemia/insulin resistance may be responsible for the elevation of sE-selectin levels.

E-Selectin↗
PubMed2000

Membranous lipodystrophy presenting with palilalia: a PET study of cerebral glucose metabolism.

A case of membranous lipodystrophy (Nasu-Hakola disease; NHD) associated with palilalia was reported. A 38-year-old Japanese woman developed walking difficulty in her twenties. At age 35 she manifested neuropsychiatric symptoms characterized by euphoria, palilalia and dementia. A bone marrow biopsy showed periodic acid Schiff-positive membranous cystic lesions in the adipose tissue. Positron emission tomography with (18F)-2-fluoro-2-deoxy-D-glucose disclosed that regional cerebral glucose metabolism was decreased in the bilateral frontal white matter with mild hypometabolism in the thalamus and basal ganglia; all predominantly on the right. Taken together with the previous postmortem findings, it is postulated that frontal lobe hypofunction, predominantly in the right hemisphere, produced the unique neuropsychiatric symptoms in this patient.

Adult↗
PubMed2000

Increased insulin sensitivity and decreased insulin secretion in offspring of insulin-sensitive type 2 diabetic patients.

To investigate the early defects of glucose metabolism in insulin-sensitive type 2 diabetes, we performed oral and frequently sampled intravenous glucose tolerance tests (OGTT and FSIGT) with minimal model analysis in 15 offspring of Japanese type 2 diabetics with normal insulin sensitivity (insulin resistance index of homeostasis model assessment [HOMA-R] < 2.0) and in 20 healthy control subjects without a family history of type 2 diabetes. The frequency of impaired glucose tolerance (IGT) was 40% (6 of 15) in the offspring and 0% (0 of 20) in the controls. Fasting plasma glucose (4.8 +/- 0.1 v4.6 +/- 0.1 mmol/L, P = .18) and immunoreactive insulin ([IRI] 29.9 +/- 2.5 v 28.3 +/- 2.5 pmol/L, P = .64) were comparable between the offspring and the controls. The rate of glucose disappearance (KG) was significantly lower in the offspring versus the control group (2.00 +/- 0.22 v 2.60 +/- 0.17 min(-1), P= .03). The insulin sensitivity index (Si) was significantly greater in the offspring versus the controls (2.68 +/- 0.41 v 1.71 +/- 0.17 x 10(-4) min(-1) x pmol/L , P = .02). First-phase insulin secretion (FPI) to intravenous glucose was significantly lower in the offspring versus the control group (886 +/- 110 v 2,296 +/- 267 min x pmol/L, P< .01). Glucose effectiveness (SG) was comparable between the offspring and control groups. The disposition index (Si x FPI) was significantly lower in the offspring versus the controls (2,106 +/- 256 v 3,652 +/- 490 x 10(-4), P = .02). When the offspring were subdivided into 2 groups by glucose tolerance status, both normal glucose tolerance (NGT) offspring and IGT offspring showed a significant decrease in FPI and increase in Si. Thus, although the offspring of insulin-sensitive type 2 diabetics had increased insulin sensitivity, the impairment in insulin secretion was more dominant. Our results suggest that the early metabolic abnormality in insulin-sensitive type 2 diabetes is an insulin secretory dysfunction despite increased insulin sensitivity.

Adult↗
PubMed2000

Evaluation of filtration leucocytapheresis for use in the treatment of patients with rheumatoid arthritis.

OBJECTIVES: To evaluate the efficacy of filtration leucocytapheresis (LCP) for rheumatoid arthritis (RA). METHODS: LCP was carried out three times, with 1 week separating each session, in 25 drug-resistant RA patients. RESULTS: During each session, 96, 98, 61, 84 and 8% of the granulocytes, monocytes, lymphocytes, platelets and erythrocytes, respectively, that entered the LCP filter were removed. The number of granulocytes, monocytes and lymphocytes in the peripheral blood significantly decreased during each session of LCP. However, there was no significant decrease in the number of circulating blood cells during the study period. On average, 110 x 10(8) granulocytes, 5.23 x 10(8) monocytes, and 20.5 x 10(8) lymphocytes were removed during LCP therapy. Assessment of RA before and after LCP showed a substantial and rapid improvement in the tender joints counts, swollen joint counts, and patient's and physician's assessments. No adverse reactions or complications were noted. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels decreased following LCP, although the change in the latter parameter was statistically insignificant. The concentrations of serum albumin, gamma-globulin, IgG, IgM, CH50 and rheumatoid factor titres did not change during or after LCP. Careful analysis indicated that 16 of 25 patients with RA showed > or =20% improvement following LCP therapy. CONCLUSIONS: Our results suggest that filtration LCP to remove leucocytes from the peripheral blood exerts an immunomodulatory effect in patients with RA.

Arthritis, Rheumatoid↗
PubMed2000

[A case of non-convulsive status epilepticus worsened Wernicke's aphasia reversely].

A 62-year-old right-handed woman had presented progressive speech impediment over 4 months. She was alert without any convulsions or involuntary movements. Neurological examination showed Wernicke's aphasia, constructional apraxia. Her magnetic resonance imaging (MRI) showed an old cerebral infarction in the left parieto-occipital area, in addition to ischemic changes in the bilateral deep white matter. Electroencephalography (EEG) revealed periodic lateralized epileptiform discharges (PLEDs) predominant in the posterior left hemisphere. The PLEDs as well as the cortical symptoms improved after an administration of anti-convulsive agents, thus establishing the diagnosis of non-convulsive status epilepticus (NSE). It should be emphasized that NSE manifesting as Wernicke's aphasia should be distinguished from dementia syndrome because it is a treatable disorder.

Anticonvulsants↗
PubMed1999

Antithrombotic effect of SM-20302, a nonpeptide GPIIb/IIIa antagonist, in a photochemically induced thrombosis model in guinea pigs.

SM-20302, a synthetic inhibitor of the fibrinogen receptor of platelets, has been shown to inhibit the platelet aggregation induced by various stimuli. In the present study, we performed ex vivo platelet aggregation studies by using heparinized platelet-rich plasma (PRP) as well as citrated PRP and compared the antiaggregatory activity with the in vivo antithrombotic efficacy of SM-20302. The oral administration of SM-20302 (0.3-10 mg/kg) to guinea pigs completely inhibited the ADP-induced ex vivo platelet aggregation in citrated PRP. In heparinized PRP, SM-20302 (1-10 mg/kg) showed a dose-dependent inhibition of ex vivo platelet aggregation, and it exhibited complete inhibition at a dose of 3 and 10 mg/kg, respectively. The concentration of ionized calcium in the citrated samples was approximately 35 times lower than that in heparinized samples. Chelation of ionized calcium caused an enhancement of the antiaggregatory activity of SM-20302 in guinea pig heparinized PRP in vitro. And addition of CaCl2 to citrated PRP reversed the enhancement. Citrate therefore appeared to enhance the inhibitory activity of SM-20302 by lowering the ionized calcium levels. We also examined the in vivo efficacy of SM-20302 in a photochemically induced femoral artery thrombosis model in guinea pigs. The photochemical injury of the endothelium of femoral artery resulted in a progressive decline in the blood flow. The oral administration of SM-20302 (0.1-3 mg/kg) produced a dose-dependent maintenance of the femoral artery patency and significantly prolonged the time to occlusive thrombus formation at a dose of 1 and 3 mg/kg, respectively. These results suggest that SM-20302 may be an orally active antithrombotic agent, and its in vivo antithrombotic efficacy appeared to correlate well with the ex vivo platelet inhibition in PRP prepared from heparinized blood but not in PRP anticoagulated with citrate.

Adenosine Diphosphate↗
PubMed1999

Relationships between apolipoprotein(a) phenotype and increase of lipoprotein(a) by troglitazone.

Troglitazone is a new oral hypoglycemic agent that reduces insulin resistance in non-insulin-dependent diabetes mellitus (NIDDM). However, this agent increases serum lipoprotein(a) [Lp(a)], which is known as an atherogenic lipoprotein. The relationships between the response of Lp(a) to troglitazone and the apolipoprotein(a) [apo(a)] phenotype were investigated in this study. Nineteen NIDDM patients were treated with troglitazone for 4 weeks. Lp(a) increased significantly from 20.1+/-16.5 mg/dL to 44.1+/-31.9 mg/dL (P<.001) in all study patients. Lp(a) increased from 25.7+/-34.2 mg/dL to 50.1+/-38.7 mg/dL (P = .03) in patients with smaller apo(a) phenotypes (S1S4 to S2S4). Lp(a) also increased from 17.5+/-12.0 mg/dL to 41.3+/-29.6 mg/dL (P<.01) in patients with larger apo(a) phenotypes (S3 to S4). Therefore, the increase of Lp(a) by troglitazone may be independent of the apo(a) phenotype.

Adult↗
PubMed1999

Argatroban increases nitric oxide levels in patients with peripheral arterial obstructive disease: placebo-controlled study.

Intravenous argatroban infusion therapy is widely used for the restoration of peripheral microcirculation in patients with peripheral arterial obstructive disease (PAOD). We investigated the effect of argatroban infusion therapy on plasma levels of nitric oxide (NO) and nitrosylhemoglobin (HbNO) in patients with PAOD compared with a placebo-treated PAOD group. The chemiluminescence method was used to determine plasma NO and HbNO. Argatroban was administered as a continuous intravenous infusion for 60 minutes and repeated daily over a period of 2 weeks in 10 patients with PAOD. Treatment significantly improved the clinical signs and symptoms. Serial thermograms showed a 1-2 degrees C rise in the temperature of the affected legs in all patients immediately after intravenous argatroban infusion therapy. Enhancement of the peripheral circulation was maintained after the end of argatroban infusion for up to 90 minutes despite elimination of argatroban from the circulation. Furthermore, there was a progressive and significant increase in the mean concentration of plasma NO in PAOD patients after commencement of argatroban infusion (baseline, 58.0 +/- 13. 7;90 minutes after infusion, 65.7 +/- 13.4 microM; P < 0.01). HbNO significantly increased from a baseline value of 1063 +/- 126 to 1460 +/- 250 nM at 30 minutes after infusion (P < 0.01). However, the level of HbNo decreased thereafter, although it remained significantly elevated, even at 90 minutes after the end of argatroban infusion. Our results suggest that argatroban may lead to increased HbNO and plasma NO, and this may contribute to the improved microcirculation in PAOD patients.

Aged↗
PubMed1999

A gene for fluctuating, progressive autosomal dominant nonsyndromic hearing loss, DFNA16, maps to chromosome 2q23-24.3.

The sixteenth gene to cause autosomal dominant nonsyndromic hearing loss (ADNSHL), DFNA16, maps to chromosome 2q23-24.3 and is tightly linked to markers in the D2S2380-D2S335 interval. DFNA16 is unique in that it results in the only form of ADNSHL in which the phenotype includes rapidly progressing and fluctuating hearing loss that appears to respond to steroid therapy. This observation suggests that it may be possible to stabilize hearing through medical intervention, once the biophysiology of deafness due to DFNA16 is clarified. Especially intriguing is the localization of several voltage-gated sodium-channel genes to the DFNA16 interval. These cationic channels are excellent positional and functional DFNA16 candidate genes.

Adolescent↗
PubMed1999

Does the production of nitric oxide contribute to the early improvement after a single low-density lipoprotein apheresis in patients with peripheral arterial obstructive disease?

Low-density lipoprotein (LDL) adsorption using a dextran sulfate cellulose (DSC) column is commonly performed for extracorporeal removal of LDL in hypercholesterolemic patients with peripheral arterial obstructive disease. We investigated whether the use of heparin or nafamostat mesilate as anticoagulants in a single LDL apheresis produced different clinical effects, or brought about the production of bradykinin and endogenous nitric oxide (NO) in these patients. LDL apheresis was performed in ten patients with peripheral arterial obstructive disease. We measured plasma levels of bradykinin, NO and nitrosylhemoglobin as well as skin temperature. Plasma levels of bradykinin increased 12-fold during LDL apheresis with heparin, but did not increase during LDL apheresis with nafamostat mesilate. LDL adsorption resulted in an immediate rise in skin temperatures (1-2 degrees C) of the lower ischemic legs irrespective of the type of anticoagulant used, and this persisted after the end of LDL apheresis for up to 60 min. There was a progressive and significant increase in plasma NO after the commencement of single LDL apheresis in both groups (heparin group: 64.0 +/- 17.3 micromol/l at baseline, 73.3 +/- 15.2 micromol/l 60 min after apheresis, P<0.005; nafamostat mesilate group: 65.0 +/- 18.8 micromol/l at baseline, 75.5 +/- 17.5 micromol/l 60 min after apheresis, P<0.001). On the other hand, levels of nitrosylhemoglobin increased significantly after 1000 ml of plasma treatment but the level decreased thereafter, although it was significantly higher than baseline 60 min after LDL apheresis. Our results suggest that a single LDL apheresis enhanced peripheral microcirculation, probably as a result of increased production of NO, irrespective of changes in bradykinin release.

Aged↗
PubMed1999

Insulin resistance and classic risk factors in type 2 diabetic patients with different subtypes of ischemic stroke.

OBJECTIVE: In addition to classic risk factors (e.g., hypertension), insulin resistance is an important risk factor for the development of atherosclerosis. To investigate the risk factors for ischemic stroke in type 2 diabetes, we measured insulin sensitivity and several risk factors in 94 Japanese type 2 diabetic patients with different types of stroke. RESEARCH DESIGN AND METHODS: Stroke was classified by magnetic resonance imaging (MRI) and magnetic resonance (MR) angiography into the following subtypes: 1) patients with normal MRI and MR angiography (NOR; n = 30), 2) patients with lacunar infarction (LAC; n = 28), 3) patients with atherothrombotic infarction (ATI; n = 22), and 4) patients with large-artery atherosclerosis (LAA; n = 14). Insulin sensitivity was assessed by the K index of the insulin tolerance test (KITT). RESULTS: Patients with LAC, ATI, and LAA were significantly older and were more likely to be hypertensive than patients with NOR. Significantly higher insulin resistance was observed in patients with LAC, ATI, and LAA than in patients with NOR (KITT 2.21 +/- 0.17, 2.10 +/- 0.17, 2.19 +/- 0.25, and 3.25 +/- 0.21% per min, respectively, P < 0.001). Adjustment for age, sex, BMI, and duration of diabetes did not influence this result. Multiple logistical regression analysis showed that insulin resistance was an independent risk factor for all subtypes of ischemic stroke in type 2 diabetic patients. The same analysis showed that a high pulse pressure was a risk factor for LAC, postprandial C-peptide (hyperinsulinemia) was a risk factor for ATI, and longstanding hyperglycemia was a risk factor for LAA.

Age Factors↗