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Biomedical subjects

S Miyake

Publications and source records attributed to S Miyake.

At least 19 recordsLinked to original sources
PubMed2002

Comparison of serum concentrations of soluble adhesion molecules in diabetic microangiopathy and macroangiopathy.

AIMS: To clarify the correlation between serum concentrations of soluble adhesion molecules and diabetic microangiopathy or macroangiopathy in patients with Type 2 diabetes. METHODS: Patients with diabetic retinopathy and intima-media thickness of common carotid artery (CCA-IMT) < 1.1 mm were classified as the microangiopathy group (n = 62). Patients with CCA-IMT > or = 1.1 mm and without retinopathy were classified as the macroangiopathy group (n = 95). Patients with CCA-IMT < 0.9 mm and without retinopathy were assigned to the no complications group (n = 139). Clinical characteristics and soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin levels were compared between the groups. RESULTS: Patients with microangiopathy had a significantly longer duration of diabetes, were hypertensive and more likely to have a positive family history of diabetes than the control group. Patients with macroangiopathy were more likely to be smokers, hypertensive, and have a family history of hypertension. Soluble ICAM-1, VCAM-1, and E-selectin levels were significantly higher in the microangiopathy group than in the control group. Soluble VCAM-1 and E-selectin levels, but not ICAM-1 levels, were significantly elevated in the macroangiopathy group. These results were unchanged after adjustment for age, sex, duration of diabetes, blood pressure, HbA1c, HDL-cholesterol, and smoking status. CONCLUSIONS: Our results suggest that soluble adhesion molecules are related to both diabetic micro- and macroangiopathy. The relative contributions of adhesion molecules may be greater in the former than latter patients with Type 2 diabetes.

Aged↗
PubMed2002

NOR-1: a nitric oxide releasing agent for calibrating low levels of nitric oxide by the chemiluminescence method.

Nitric oxide (NO) is formed in small amounts in vivo and is rapidly oxidized by interacting with oxygen, making measurement of its level difficult. The chemiluminescence assay is the most widely used method for detecting NO and is extremely sensitive to very small amounts of NO. However, it is difficult to prepare small amounts of NO to be used as a standard for NO analysis. NOR-1, a derivative of NOR-3, is a newly discovered NO donor with rapid NO-releasing activity. We assessed the dynamics of NO release and decomposition using NOR-1. Our results demonstrate that NOR-1 is stable in dimethylsulfoxide (DMSO) and is able to dilute at lower concentration (to picomolar levels) by DMSO without decomposition. NOR-1 released persistently 1.4 more excess of NO with 15 min of incubation. There was a linear relationship between the concentration of NOR-1 and that of NO released from NOR-1 (r=0.997) These findings suggest that NOR-1 is a useful reagent for the calibration of lower NO detection.

Benzoates↗
PubMed2002

[Clinical evaluation of filtration leukocytapheresis(LCAP) in rheumatoid arthritis(RA)].

Filtration Leukocytapheresis(LCAP) is an alternative to thoracic duct drainage and LCAP using a centrifuge method with the advantages that it can be performed easily and inexpensively. Clinical trials revealed that LCAP is a safe and effective therapy for patients with drug-resistant rheumatoid arthritis(RA). Assessment of RA before and after LCAP showed a substantial and rapid improvement in tender joints counts, swollen joint counts, and patient's and physician's assessments. Careful analysis indicated that 64-80% of patients with RA showed > or = 20% improvement following LCAP therapy. Furthermore, we investigated the clinical evaluation of LCAP for RA over the 3 year-study period. Possible therapeutic mechanisms of LCAP on RA are summarized.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2001

Individual differences in tracking.

The present experiment compared differences in response strategy of participants performing a two-dimensional tracking task at three different levels of task difficulty. Twelve participants tracked an iconic aeroplane target as accurately as possible for nine repeated trials each of 5 min duration. The random input and individual response output were calculated in terms of direction and velocity. Specifically, for each 200-ms sample period, a calculated combination of eight trajectories and three velocities provided a 24 combinatorial description of both random input and participant response. Distributions across these combinations represent descriptive results and reflect individual characteristics. The distributions were compared using the technique of correspondence factor analysis. The outcome of this multidimensional method was that first, between-participants discrimination was best served by the up-vertical and low-velocity combination and, second, that the former pattern typified poor performers, while more skilled individuals used all directional options at the highest velocity level. Implications for individualized controls are examined.

Adult↗
PubMed2001

A synthetic glycolipid prevents autoimmune encephalomyelitis by inducing TH2 bias of natural killer T cells.

Experimental autoimmune encephalomyelitis (EAE) is a prototype autoimmune disease mediated by type 1 helper T (TH1) cells and under the control of regulatory cells. Here we report that a synthetic glycolipid ligand for CD1d-restricted natural killer T (NKT) cells expressing the semi-invariant T-cell receptor (Valpha14+) is preventive against EAE. The ligand is an analogue of alpha-galactosylceramide (alpha-GC), a prototype NKT cell ligand, with a truncated sphingosine chain. alpha-GC causes NKT cells to produce both interferon (IFN)-gamma and interleukin (IL)-4 (refs 4, 5). However, this new ligand can induce a predominant production of IL-4 by the NKT cells. A single injection of this glycolipid, but not of alpha-GC, consistently induced TH2 bias of autoimmune T cells by causing NKT cells to produce IL-4, leading to suppression of EAE. The lack of polymorphism of CD1d and cross-reactive response of mouse and human NKT cells to the same ligand indicates that targeting NKT cells with this ligand may be an attractive means for intervening in human autoimmune diseases such as multiple sclerosis.

Amino Acid Sequence↗
PubMed2001

Risk factors for distant recurrence of hepatocellular carcinoma in the liver after complete coagulation by microwave or radiofrequency ablation.

BACKGROUND: In patients with hepatocellular carcinoma (HCC), recurrences in the distant liver often are observed after curative treatment. Microwave coagulation therapy (MCT) and radiofrequency ablation (RFA) have been developed as less invasive alternatives than surgical resection for small HCCs. In the current study, risk factors for distant recurrence of HCC were analyzed in patients in whom complete coagulation was achieved. METHODS: Ninety-two patients with HCCs < 3 cm in greatest dimension were treated by MCT or RFA percutaneously or laparoscopically. Eighty-four patients in whom complete coagulation was achieved without recurrence in the same subsegment as the primary nodule were included in this study. Distant recurrences were observed in 22 patients. Fifteen possible risk factors for a distant recurrence were analyzed. RESULTS: When comparing the patients with a recurrence of HCC nodules in the remnant liver to those without recurrence, the authors observed a statistically significant difference only in serum alpha-fetoprotein. The distant recurrence-free survival was analyzed by the Kaplan-Meier method. A statistically significant difference was observed in hepatitis C virus (HCV) infection as an etiopathic agent of underlying liver diseases (P < 0.005) and in the number of the primary HCC nodules (P < 0.05, log-rank test). A multivariate stepwise Cox hazard model revealed that HCV infection and the number of primary HCC nodules were statistically independent risk factors. CONCLUSIONS: Patients who had more than two HCC nodules accompanied by HCV infection had a high incidence of recurrence of HCC in the remnant liver, even when coagulation by microwave or ablation by radiofrequency was complete.

Aged↗
PubMed2001

Costimulation-dependent modulation of experimental autoimmune encephalomyelitis by ligand stimulation of V alpha 14 NK T cells.

Experimental autoimmune encephalomyelitis (EAE) is a Th1 cell-mediated autoimmune disease that can be protected against by stimulating regulatory cells. Here we examined whether EAE can be purposefully modulated by stimulating Valpha14 NK T cells with the CD1d-restricted ligand alpha-galactosylceramide (alpha-GC). EAE induced in wild-type C57BL/6 (B6) mice was not appreciably altered by injection of alpha-GC. However, EAE induced in IL-4 knockout mice and IFN-gamma knockout mice was enhanced or suppressed by alpha-GC, respectively. This indicates that the IL-4 and IFN-gamma triggered by alpha-GC may play an inhibitory or enhancing role in the regulation of EAE. We next studied whether NK T cells of wild-type mice may switch their Th0-like phenotype toward Th1 or Th2. Notably, in the presence of blocking B7.2 (CD86) mAb, alpha-GC stimulation could bias the cytokine profile of NK T cells toward Th2, whereas presentation of alpha-GC by CD40-activated APC induced a Th1 shift of NK T cells. Furthermore, transfer of the alpha-GC-pulsed APC preparations suppressed or enhanced EAE according to their ability to polarize NK T cells toward Th2 or Th1 in vitro. These results have important implications for understanding the role of NK T cells in autoimmunity and for designing a therapeutic strategy targeting NK T cells.

Amino Acid Sequence↗
PubMed2001

Enhanced disruption of the blood-aqueous barrier and the incidence of angiographic cystoid macular edema by topical timolol and its preservative in early postoperative pseudophakia.

OBJECTIVE: To investigate the effects of timolol maleate with preservative and its preserved (PV) and nonpreserved vehicles (NPV) (benzalkonium chloride) on the blood-aqueous barrier and angiographic cystoid macular edema (CME) in early postoperative pseudophakia. PATIENTS AND METHODS: Patients with ocular hypertension, normal tension glaucoma, and primary open-angle glaucoma who underwent surgery for cataracts. The study included a double-masked trial for timolol, PV, and NPV and a single-masked trial on the effect of diclofenac sodium and fluorometholone acetate on all three. The patients were divided into 6 groups, each of which were simultaneously administered the following different combinations of compounds: timolol and diclofenac (group A), timolol and fluorometholone (group B), PV and diclofenac (group C), PV and fluorometholone (group D), NPV and diclofenac (group E), and NPV and fluorometholone (group F). The 6 groups were then compared using a laser flare cell meter to determine the degree of disruption of the blood-aqueous barrier and fluorescein angiography to investigate angiographic CME. The differences in mean daily fluctuations in intraocular pressure were compared on the preoperative baseline day and for 5 weeks postoperatively. Twice daily administration of 0.5% timolol maleate or the vehicles was started 2 days before surgery, and continued until 5 weeks after surgery. Diclofenac or fluorometholone drops were instilled in the eyes 4 times preoperatively, on the day of surgery, and 3 times daily for 5 weeks postoperatively. RESULTS: The flare amount was higher on the third and seventh days in group B than in group D, but was the same after the seventh day. The incidence of angiographic CME was the same between both groups. These 2 factors were significantly lower in group F. These 2 factors were also significantly lower in the 3 groups that received diclofenac instead of fluorometholone, with no difference among these groups. The intraocular pressure decline was significant in groups that received timolol compared with groups that received PV or NPV. CONCLUSIONS: Timolol and its preservative, benzalkonium chloride, cause disruption of the blood-aqueous barrier in early postoperative pseudophakia and increased incidence of angiographic CME. The concurrent administration of nonsteroidal anti-inflammatory drug such as diclofenac prevents these adverse effects without interfering with the drop in intraocular pressure caused by timolol. The addition of benzalkonium chloride to timolol contributes considerably to these adverse effects. CLINICAL RELEVANCE: The present results suggest the cause of similar complications produced by other antiglaucoma eyedrops containing similar preservatives.

Administration, Topical↗
PubMed2001

Multivariate workload evaluation combining physiological and subjective measures.

This paper suggests a way to integrate different parameters into one index and results obtained by a newly developed index. The multivariate workload evaluation index, which integrates physiological parameters and one subjective parameter through Principle Components Analysis, was proposed to characterize task specific responses and individual differences in response patterns to mental tasks. Three different types of mental tasks were performed by 12 male participants. Heart rate variability, finger plethysmogram amplitude, and perspiration were used as physiological parameters. Three subscales, mental demand, temporal demand and effort out of six subscales in the NASA-Task Load Index were used as subjective scores. These parameters were standardized within each participant and then combined. It was possible to assess workload using this method from two different aspects, i.e. physiological and subjective, simultaneously.

Adolescent↗
PubMed2001

Insulin resistance and coronary risk factors in Japanese type 2 diabetic patients with definite coronary artery disease.

Insulin resistance is known as an important risk factor for coronary artery disease (CAD). However, CAD-related mortality in Japanese type 2 diabetics is lower than in Caucasians. To investigate whether insulin resistance is related to CAD in Japanese type 2 diabetics, we measured insulin sensitivity and several coronary risk factors in Japanese patients with type 2 diabetes with and without CAD. Thirty-three patients with definite CAD and 33 age- and sex-matched patients without CAD (control) were studied. Insulin sensitivity was assessed by the K index of insulin tolerance test (KITT). Clinical characteristics, classical risk factors, lipoprotein (a), and insulin sensitivity were compared between the two groups. Patients with CAD had a significantly longer duration of diabetes (9.0 +/- 1.4 vs. 5.5 +/- 0.9 years, P < 0.05, respectively), were mostly hypertensive (69.7 vs. 39.4%, P < 0.05), and more likely to be treated with insulin (45.5 vs. 18.2%, P < 0.05) compared with the control. Concerning the metabolic parameters, patients with CAD had a significantly higher insulin resistance than control (2.40 +/- 0.15 vs. 3.23 +/- 0.17%/min, P < 0.01, respectively), higher triglyceride (1.39 +/- 0.10 vs. 1.05 +/- 0.05 mmol/l, P < 0.05), lower HDL cholesterol (1.05 +/- 0.05 vs. 1.28 +/- 0.06 mmol/l, P < 0.05), and higher lipoprotein (a) (27.5 +/- 4.3 vs. 17.4 +/- 2.0 mg/dl, P < 0.05). Multiple logistic regression analysis indicated that hypertension, insulin resistance, high lipoprotein (a) and triglyceride, and low HDL cholesterol were independently related to CAD. Our results suggest that insulin resistance per se is a significant risk factor for CAD in Japanese patients with type 2 diabetes.

Aged↗
PubMed2001

Correction of hyperglycaemia reduces insulin resistance and serum soluble E-selectin levels in patients with Type 2 diabetes mellitus.

AIMS: To investigate the effects of glycaemic control on insulin sensitivity and serum concentrations of soluble vascular cell adhesion molecule (sVCAM)-1 and E-selectin (sE-selectin) in patients with Type 2 diabetes mellitus. To examine whether reductions in serum adhesion molecule levels correlate with improvement in insulin resistance. METHODS: A total of 54 patients with Type 2 diabetes were treated for 4 weeks with either diet alone, sulphonylurea or insulin. Fasting glucose, insulin sensitivity, lipids, sVCAM-1, and sE-selectin levels were measured before and after treatment. RESULTS: All treatment modalities successfully corrected hyperglycemia. Reductions in blood glucose levels resulted in improvement in insulin sensitivity (diet KITT 2.40 +/- 0.26-3.09 +/- 0.36, P < 0.01; sulphonylurea 2.24 +/- 0.16-2.94 +/- 0.18, P < 0.01; insulin 1.68 +/- 0.27-2.16 +/- 0.22%/min, P < 0.05), and decrease in sE-selectin levels (diet 88.4 +/- 14.9-66.2 +/- 10.8, P < 0.05; sulphonylurea 85.1 +/- 11.6-59.8 +/- 7.8, P < 0.01; insulin 84.4 +/- 8.7-66.8 +/- 7.4 ng/ml, P < 0.01), but no change in sVCAM-1 levels. There was a significant correlation between the degree of decrease in sE-selectin levels and improvement in insulin sensitivity (r = -0.38, P < 0.01). CONCLUSIONS: Correction of hyperglycaemia, independent of treatment modality, resulted in improvement of insulin resistance and decrease in sE-selectin levels. These changes might, in part, contribute to reduce the risk of diabetic microvascular and macrovascular complications in patients with Type 2 diabetes mellitus.

Biomarkers↗
PubMed2001

Comparison of lymphocyte depletion and clinical effectiveness on filtration leukocytapheresis in patients with rheumatoid arthritis.

We evaluated the relationship between the clinical benefit of filtration leukocytapheresis (LCP) and the number of removed leukocytes in patients with rheumatoid arthritis (RA). LCP was performed in 31 drug-resistant RA patients. LCP was carried out 3 times with 1 week separating each session. Assessment of RA before and after LCP showed a substantial and rapid improvement in tender joint counts, swollen joint counts, and patients' and physicians' assessments. Careful analysis indicated that 19 of 31 patients with RA showed > or = 20% improvement following LCP therapy. The number of leukocytes 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. No adverse reactions or complications were noted. There was no significant difference in any indices of clinical activity and the removal rates of leukocytes between responders and nonresponders. The total numbers of removed lymphocytes in responders were significantly higher than those in nonresponders (responders 64.1 x 10(8) versus nonresponders 50.7 x10(8), p < 0.05). The relationship between clinical effectiveness and the number of removed granulocytes and monocytes was not statistically significant. Our results suggest that filtration LCP to remove leukocytes from the peripheral blood, especially lymphocytes, exerts an immunomodulatory effect in patients with RA.

Adult↗
PubMed2001

A potent antiviral effect on hepatitis C viral dynamics in serum and peripheral blood mononuclear cells during combination therapy with high-dose daily interferon alfa plus ribavirin and intravenous twice-daily treatment with interferon beta.

Hepatitis C virus (HCV) is known to infect and replicate within peripheral blood mononuclear cells (PBMC), thereby enabling the direct evaluation of antiviral mechanisms by analyzing HCV dynamics in PBMC. To address potential molecular differences associated with distinct antiviral regimens, we studied HCV dynamics in both serum and PBMC in 44 patients with HCV genotype 1b and high viral load who were randomly assigned to the following 4 different treatment groups: 1) combination therapy with 6 MU daily of interferon alfa 2b (IFN-alpha2b) plus 800 mg of ribavirin; 2) monotherapy with 6 MU daily of IFN-alpha2b; 3) monotherapy with twice-daily intravenous administration with 3MU of IFN-beta; and 4) monotherapy with daily intravenous administration with 6 MU of IFN-beta. HCV-RNA levels were measured serially using highly sensitive real-time detection polymerase chain reaction (PCR). HCV dynamics in both the serum and PBMC showed a "biphasic" pattern. The exponential decay slopes of the second phase were significantly higher in the combination or twice-daily dosing regimen groups compared with groups 2 or 4 (0.10 +/- 0.08 vs. 0.02 +/- 0.09 or 0.16 +/- 0.09 vs. 0.02 +/- 0.04 day(-1); P <.05 or P <.0005, respectively). Moreover, the viral half-lives in the second phase were significantly shorter in these groups (73.2 +/- 42.5 vs. 240.1 +/- 120.7 or 56.0 +/- 44.6 vs. 361.6 +/- 293.5 hours; P <.05 or P <.05, respectively). Additionally, the slope of HCV decline in PBMC tended to be higher in the combination regimens, as compared with monotherapy. Taken together, our data on HCV dynamics provide molecular insight into utilization of combination or twice-daily dosing regimens to increase rates of sustained viral eradication of HCV.

Adult↗
PubMed2001

The effects of bisoprolol, a selective beta1-blocker, on glucose metabolism by long-term administration in essential hypertension.

Bisoprolol, a beta1-selective beta-blocker, was administered to 13 patients with mild to moderate essential hypertension once daily at doses of 5-10 mg for 24 weeks, and its long-term effects on blood pressure and glucose metabolism were investigated. The systolic, diastolic and mean blood pressures were significantly reduced. At the end of the treatment period, the blood glucose level and hemoglobin A1c were not significantly different from those at baseline. In the glucose tolerance test at the end of the treatment period, the blood glucose and plasma insulin levels after a glucose load of 75 g were not significantly different at any time point, and the sums of each were not significantly different from their baseline levels. Based on these results, bisoprolol appears to be a beta1-selective beta-blocker possessing a satisfactory hypotensive effect without any adverse effects on glucose metabolism for long-term use, and is therefore a safe and useful drug for the treatment of essential hypertension.

Adrenergic beta-Antagonists↗
PubMed2001

CPT-11 may provide therapeutic efficacy for esophageal squamous cell cancer and the effects correlate with the level of DNA topoisomerase I protein.

CPT-11 is a potent anti-cancer drug and a specific inhibitor of DNA topoisomerase I (Topo I). In this study, we aim to evaluate the effects of CPT-11 on esophageal squamous cell cancers (ESCC) and to determine the correlation between the effects and the levels of Topo I expression. We examined the growth-inhibitory effect caused by SN-38, an active metabolite of CPT-11, in 14 human ESCC cell lines established from 10 primary and 4 metastatic lesions. CPT-11 was considered effective against 5 cell lines from primary lesions and one from metastatic lesions, and thus may show therapeutic efficacy against both primary and metastatic ESCC tumors. Although Topo I mRNA levels in these 14 ESCC cell lines, as quantitated by northern blot analysis, showed no correlation with the IC(50) values, Topo I protein levels, as quantitated by western blot analysis, showed an inverse correlation with the IC(50) values. Topo I protein levels could be an indicator of sensitivity to CPT-11. We also determined Topo I protein levels in 40 ESCC tumors and matched normal mucosae. Thirty-four tumors showed 1.2 - 22.3-fold increases in Topo I levels. Two patients receiving pre-operative chemotherapy and one receiving radiotherapy exhibited increased Topo I protein levels in their tumor lesions. It appeared that CPT-11 could provide selective therapeutic efficacy against ESCC tumors. CPT-11 may be effective for the treatment of metastatic ESCC tumors and as a second-line anti-cancer drug for ESCC.

Blotting, Western↗
PubMed2001

Natural killer type 2 bias in remission of multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune disease characterized by clinical relapse and remission. Because of the potential role of natural killer (NK) cells in the regulation of autoimmunity, we have examined cytokine profile and surface phenotype of NK cells in the peripheral blood of MS. Here we demonstrate that NK cells in the remission of MS are characterized by a remarkable elevation of IL-5 mRNA and a decreased expression of IL-12Rbeta2 mRNA, as well as a higher expression of CD95. Moreover, the NK cells from MS in remission produced much larger amounts of IL-5 than did those from controls after stimulation with phorbol myristate acetate (PMA) and ionomycin. These features are reminiscent of those of NK type 2 (NK2) cells that can be induced in a condition favoring functional deviation of T cells toward Th2. Remarkably, the NK cells lose the NK2-like property when relapse of MS occurs, but regain it after recovery. We also found that NK2 cells induced in vitro inhibit induction of Th1 cells, suggesting that the NK2-like cells in vivo may also prohibit autoimmune effector T cells. Taken together, it is possible that NK cells play an active role in maintaining the remission of MS.

Adult↗