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Biomedical subjects

Y Aso

Publications and source records attributed to Y Aso.

At least 19 recordsLinked to original sources
PubMed2004

Enhancement of fibrinolysis in poorly controlled, hospitalized type 2 diabetic patients by short-term metabolic control: association with a decrease in plasminogen activator inhibitor 1.

Impaired fibrinolysis in type 2 diabetes may be caused by an increased plasma concentration of plasminogen activator inhibitor 1 (PAI-1), although the effects of short-term hypoglycemic therapy on fibrinolytic activity are poorly understood. This study investigated the effects of metabolic improvement on fibrinolysis activity and plasma concentrations of PAI-1 in poorly controlled, hospitalized type 2 diabetic patients. Forty-eight poorly controlled type 2 diabetic patients were studied; 26 were subsequently treated with sulfonylurea (SU) and 22 with insulin. The plasma concentrations of plasmin-alpha2-antiplasmin (PAP), a measure of fibrinolytic activity, plasma PAI-1, and fasting triglycerides and glucoses were measured at the beginning and the end of hospitalization. The body mass index and fasting triglyceride decreased significantly after treatment (p < 0.0001). The plasma concentration of PAP increased significantly (p < 0.01), and the plasma PAI-1 decreased by 50% after treatment. There was an inverse correlation between the changes in the plasma concentrations of PAP and PAI-1 (r= - 0.36, p = 0.023). Treatment with SU or insulin showed an increase in plasma PAP with a concomitant decrease in the plasma PAI-1 with equivalent glycemic control. In poorly controlled type 2 diabetic patients, the plasma PAP concentration can be significantly increased and the plasma PAI-1 antigen significantly reduced, even with short-term metabolic improvements including weight reduction, a better lipid profile, and tighter glycemic control with either SU or insulin therapy, and that enhanced fibrinolysis may be mediated partly through a decrease in the plasma PAI-1 after metabolic control.

Adult↗
PubMed2003

A prospective and randomized study of primary hormonal therapy for patients with localized or locally advanced prostate cancer unsuitable for radical prostatectomy: results of the 5-year follow-up.

OBJECTIVE: To evaluate the effect of primary hormonal therapy for patients with localized and locally advanced prostate cancer. PATIENTS AND METHODS: Patients with stage T1b-T3 prostate cancer who were not scheduled for radical prostatectomy were allocated into two groups: group 1 (73 men) received luteinizing hormone-releasing hormone (LHRH) agonist monotherapy and group 2 (78 men) received LHRH agonist and chlormadinone acetate. Patients were followed using serum prostate specific antigen levels, prostate size and the detection of distant metastasis for 5 years. RESULTS: The median (range) follow-up was 78 (63-87) months. The 5-year progression-free survival rate was significantly higher in group 2 (68%) than in group 1 (47%). However, the overall and cause-specific survival rate at 5 years were similar in both groups, at 72% and 93% in group 1, and 64% and 89% in group 2, respectively. CONCLUSION: The overall survival rates of the both groups were no different from that of the normal Japanese population of the same age group. Although this study did not include an untreated group, i.e. watchful waiting, these results might indicate the usefulness of primary hormonal therapy in controlling localized and locally advanced prostate cancer. The 5-year observation period is still short and the study is continuing to determine the 10-year survival.

Aged↗
PubMed2003

Plasma interleukin-6 is associated with coagulation in poorly controlled patients with Type 2 diabetes.

AIMS: We investigated the relationship between interleukin (IL)-6 and coagulation, i.e. whether changes in the plasma IL-6 are associated with those in coagulation markers (D dimer and fibrinogen) after glycaemic control with sulphonylurea or insulin in poorly controlled patients with Type 2 diabetes. METHODS: We studied 42 patients with Type 2 diabetes, including 19 subsequently treated with sulphonylurea, 23 treated with insulin and 48 control subjects. All patients were in poor glycaemic control and were hospitalized for 3 weeks. At the beginning and end of treatment, we measured plasma concentrations of IL-6, fibrinogen, and D dimer. RESULTS: Plasma concentrations of IL-6 and D dimer were significantly higher in diabetic patients than in controls (P<0.0001 for both). In all patients with diabetes, the plasma concentration of IL-6 decreased significantly (P<0.001) after treatment. Changes in the plasma IL-6 during hospitalization were positively correlated with those in plasma D dimer and fibrinogen (r=0.664, P<0.0001; r=0.472, P=0.0042, respectively). Treatment with sulphonylurea or insulin caused a similar fall in the plasma IL-6 concentration with a concomitant decrease in the BMI and an equal improvement in glycaemia. CONCLUSIONS: In poorly controlled patients with Type 2 diabetes, plasma IL-6 concentrations were reduced significantly even by short-term metabolic control. As changes in the plasma concentrations of D dimer are related to plasma IL-6, plasma IL-6 may reflect a pro-coagulant as well as an inflammatory state in patients with Type 2 diabetes.

Blood Coagulation↗
PubMed2003

The connection between QT dispersion and autonomic neuropathy in patients with type 2 diabetes.

It is controversial whether an increase in the QT dispersion (QTd) on the electrocardiogram (ECG) reflects cardiac autonomic neuropathy in diabetic patients. In the current study, the QTd was compared in 60 type 2 diabetic patients and in 30 healthy subjects, and its association with autonomic neuropathy in diabetic patients was investigated. An increased QTd was found in diabetic patients, compared to healthy subjects. The QTd had significant negative associations with the log of the low and high frequency power (log LF and HF, respectively) of the power spectral analyses (PSA) of heart rate variations and the systolic blood response during standing (Delta BP). There was no significant difference in the QTd between patients with and without sympathetic skin response (SSR), reflecting peripheral sympathetic function. A significant positive correlation was also found between QTd and the systolic blood pressure (SBP). On the other hand, there was no correlation between QTd and serum total cholesterol (TC), triglycerides (TG), fasting plasma glucose (FPG), hemoglobin (Hb) A (1C) concentrations or body mass index (BMI). By multiple regression analysis, the log HF, which reflects cardiac parasympathetic function, and the SBP alone were significantly associated with QTd as the dependent variable. The Delta BP and log LF, which partially reflect sympathetic nerve function, had no significant associations with QTd. These findings suggest that QTd reflects cardiac autonomic neuropathy (relative parasympathetic neuropathy) and that the QTd is also influenced by SBP, independent of autonomic neuro-function.

Adult↗
PubMed2003

Primary antiphospholipid syndrome associated with acute adrenal failure.

We describe a 48-year-old woman with primary antiphospholipid syndrome who developed acute adrenal failure after an operation for a uterine myoma. After surgery, she developed a preshock state with hypotension, hypoglycemia, and hyponatremia. A diagnosis of primary antiphospholipid syndrome was made based not only on her past history of skin ulceration and recurrent spontaneous abortions but also on the presence of anticardiolipin antibodies. An abdominal computed tomography showed a bilateral enlargement of the adrenal glands but no high-density region in either gland. The patient recovered from the shock-like syndromes after the administration of glucocorticoids. Because it is possible that patients with antiphospholipid syndrome have acute or chronic adrenal failure caused by repeated hemorrhage or thrombosis, it may be important to monitor adrenal function in patients when the presence of this antibody is detected.

Acute Disease↗
PubMed2002

Elevation of von Willebrand factor in plasma in diabetic patients with neuropathic foot ulceration.

AIMS: The present study examines the relationship between markers of endothelial dysfunction and diabetic neuropathy or consequent neuropathic foot ulceration in patients with Type 2 diabetes mellitus. METHODS: We studied 65 Type 2 diabetic patients including 25 diabetic patients without neuropathy, 27 with neuropathy but no history of foot ulceration, and 13 with neuropathic ulceration. Plasma concentrations of von Willebrand factor (vWF) and soluble thrombomodulin (TM), measures of endothelial dysfunction, were determined by enzyme immunoassays. We performed various tests quantifying aspects of diabetic neuropathy including vibration perception threshold (VPT; for sensory neuropathy), coefficient of variation of R-R intervals (CVR-R; for cardiac autonomic neuropathy), and cold-induced vasodilation in the great toe for peripheral sympathetic neuropathy. RESULTS: CVR-R and cold-induced vasodilation were significantly diminished in patients with neuropathic foot ulceration compared with patients with neuropathy but no history of foot ulceration. Plasma vWF concentrations were positively correlated with VPT and cold-induced vasodilation test, and were inversely correlated with CVR-R. Multivariate analysis disclosed that VPT and percentage vasodilation were independent factors for plasma vWF. Plasma vWF was significantly elevated in patients with foot ulceration compared with patients without neuropathy or those with neuropathy but not foot ulceration. However, plasma TM concentrations did not differ between the three groups. CONCLUSIONS: Diabetic patients with neuropathic foot ulceration had severe impairment of cardiac autonomic and peripheral sympathetic nerves. Elevation of vWF in plasma was associated with neuropathic foot ulceration, linking endothelial dysfunction to foot ulceration.

Autonomic Nervous System↗
PubMed2002

Clinical usefulness of corrected QT intervals in diabetic autonomic neuropathy in patients with type 2 diabetes.

BACKGROUND: It is recognized that QTc intervals reflect autonomic nerve function. To investigate the clinical usefulness of corrected QT intervals (QTc) in assessing autonomic nerve function in type 2 diabetes, we measured QTc intervals using Bazett's formula in 58 type 2 diabetic patients and 20 age-matched healthy subjects. METHODS: We examined relationships between QTc intervals and the coefficient of variation of RR intervals (CV(RR)), systolic blood pressure response to standing, and sympathetic skin response (SSR) whose tests reflect autonomic nerve function. We also studied the correlation between QTc and blood pressure or serum lipid concentrations. RESULTS: QTc intervals in diabetic patients were significantly longer than those in healthy subjects and showed a significant but weak negative correlation with CV(RR), as well as systolic blood pressure response to standing. No significant difference in QTc intervals was observed between patients with and without a detectable SSR. QTc intervals showed a significant positive correlation with systolic and diastolic blood pressure although it did not correlate with serum lipid concentrations. QTc also tended to be long in obese diabetic subjects (body mass index > 25). CONCLUSION: QTc intervals might also be affected by other factors such as arteriosclerotic macroangiopathy and obesity, and not only autonomic nerve function. Therefore it might be considered as an overall index for complications, and not for pure autonomic impairment.

Aged↗
PubMed2001

Atelocollagen-based gene transfer in cells allows high-throughput screening of gene functions.

We have previously demonstrated that Atelocollagen, used clinically for wound healing, is a reliable safe carrier for gene delivery. To obtain phenotypic changes by gene expression of cDNA, we developed an efficient technique for high-throughput gene transfer and expression screening in mammalian cells in microarrays by precoating a microplate with an Atelocollagen complexed with cDNA to which cells are then seeded. The complexes with a nanoparticle form were efficiently transduced into cells without use of any additional transfection reagent, and they allowed for long-term gene expression without apparent chromosomal integration. The complex spotted onto the well of a microplate was stable for a long period and allowed the cells to transduce and express reporter genes in a dose-dependent manner. We also showed that the present method using Atelocollagen-based gene transfer is applicable to gene medicines such as antisense ODNs and adenovirus vectors. These results suggest that Atelocollagen may be appropriate for general use in high-throughput screening of large sets of gene medicines for functional analyses in mammalian cells.

Adenoviridae↗
PubMed2001

Stable operation of a 300-m laser interferometer with sufficient sensitivity to detect gravitational-wave events within our galaxy.

TAMA300, an interferometric gravitational-wave detector with 300-m baseline length, has been developed and operated with sufficient sensitivity to detect gravitational-wave events within our galaxy and sufficient stability for observations; the interferometer was operated for over 10 hours stably and continuously. With a strain-equivalent noise level of h approximately 5x10(-21)/sqrt[Hz], a signal-to-noise ratio of 30 is expected for gravitational waves generated by a coalescence of 1.4M-1.4M binary neutron stars at 10 kpc distance. We evaluated the stability of the detector sensitivity with a 2-week data-taking run, collecting 160 hours of data to be analyzed in the search for gravitational waves.

Astronomy↗
PubMed2001

Explanation of the crystallization rate of amorphous nifedipine and phenobarbital from their molecular mobility as measured by (13)C nuclear magnetic resonance relaxation time and the relaxation time obtained from the heating rate dependence of the glass transition temperature.

To gain further insight into the effect of molecular mobility on the crystallization rate of amorphous drugs, the mean relaxation times of amorphous nifedipine and phenobarbital were calculated based on the Adam-Gibbs-Vogel (AGV) equation, using the parameters D, T(0), and T(f), derived from the heating rate dependence of the glass transition temperature (T(g)) of the amorphous drugs and heat capacity of the drugs in the amorphous and crystalline states. These relaxation times were compared with the crystallization rate of amorphous nifedipine and phenobarbital reported previously. The spin-lattice relaxation time (T(1)) and the spin-lattice relaxation time in the rotating frame (T(1rho)) of phenobarbital and nifedipine carbons were also determined. The temperature dependence of the crystallization rate of nifedipine and phenobarbital on the T(g) was coincident with that of the mean relaxation time calculated according to the AGV equation within experimental error, indicating that the crystallization of nifedipine and phenobarbital is largely correlated with molecular mobility at the temperatures studied. A (13)C nuclear magnetic resonance relaxation study indicated that the molecular motion of nifedipine and phenobarbital in the mid-kHz frequency range became significant at temperatures higher than T(g)-20 and T(g), respectively.

Calcium Channel Blockers↗
PubMed2001

Usefulness of the Kohlrausch-Williams-Watts stretched exponential function to describe protein aggregation in lyophilized formulations and the temperature dependence near the glass transition temperature.

PURPOSE: We studied the feasibility of using the Kohlrausch-Williams-Watts stretched exponential function (KWW equation) to describe protein aggregation in lyophilized formulations during storage. Parameters representing "mean aggregation time" (taua) and stretched exponential constant (betaa) were calculated according to the KWW equation by assuming that the time required for protein molecules to aggregate (tau) varies because of the fact that protein aggregation occurs at a rate that depends on the degree of protein deformation resulting from stresses created during freeze-drying. The temperature dependence of the parameters near the glass transition temperature was examined to discuss the possibility of predicting protein aggregation by accelerated testing. METHODS: Protein aggregation in lyophilized bovine serum gamma-globulin (BGG) formulations containing dextran or methylcellulose, at temperatures ranging from 10 to 80 degrees C, was followed by size-exclusion chromatography. RESULTS: Non-exponential BGG aggregation in lyophilized formulations could be described by the KWW equation. The taua and betaa, parameters changed abruptly around the NMR relaxation-based critical mobility temperature for formulations containing dextran and methylcellulose. In the glassy state, in contrast, the taua parameter of these formulations exhibited continuous temperature dependence. The parameter taur, as calculated from taua, and betaa, reflected differences in tau values between the two excipients. CONCLUSIONS: The results indicate that the parameter betaa is reflective of physical changes wihtin lyophilized formulations. Within the temperature range, during which no abrupt changes in betaa were observed, knowledge regarding the taua and betaa parameters allows the rate of protein aggregation to be predicted. The parameter taur was found to be useful in comparing the protein aggregation behavior of formulations having different taua and betaa values.

Algorithms↗
PubMed2001

A honeycomb collagen carrier for cell culture as a tissue engineering scaffold.

As a three-dimensional carrier for cell culture, a honeycomb structure cell scaffold was created from atelopeptide collagen Types I, II, and III. The diameter of the honeycomb pores ranged from 100 to 1,000 microm. The depth of the pores was from 10 to 3,000 mm. The scaffold was elastic and hard. Creation of various shapes was easy, and these shapes were easily maintained. Human fibroblasts, CHO-K1, BHK-21, and bovine endothelial cells were cultured with the scaffold. The growth curves of these cells were satisfactory. These results suggest that this carrier is a suitable scaffold for cell culture and will be useful as a three-dimensional tissue engineering scaffold.

Animals↗
PubMed2001

Changes in skin blood flow in type 2 diabetes induced by prostacyclin: association with ankle brachial index and plasma thrombomodulin levels.

In a previous study, we reported that beraprost sodium (BPS), a stable prostaglandin I(2) (PGI(2)) analog, increases skin blood flow in the feet of both control subjects and patients with type 2 diabetes, and that the flow increase induced by BPS is lower in diabetic patients than in controls. The present study was undertaken to clarify factors associated with smaller increases in skin blood flow in the feet of patients with type 2 diabetes after the administration of BPS, and to investigate the relationship between microalbuminuria and the changes in skin blood flow induced by the PGI(2) analog. We studied 61 patients with type 2 diabetes: 10 received placebo (control) and 51 (31 with normoalbuminuria and 20 with microalbuminuria) received BPS. Using laser Doppler flowmetry, we measured the skin blood flow at the pulp of the right big toe before and 90 minutes after administration of 40 microg BPS, and calculated the change in blood flow, i.e., delta flux (peak flux at 90 minutes - basal flux at 0 minutes). Plasma concentrations of soluble thrombomodulin (TM) were determined using an enzyme immunoassay (EIA) sandwich method. BPS significantly increased skin blood flow in the treatment group compared with the placebo group (P <.01). The delta flux was positively correlated with the value of the ankle brachial index (ABI) (r =.41, P <.0038) and was negatively correlated with plasma TM levels (r = -.53, P <.0001). By multiple regression analysis both the ABI value and the plasma TM level retained a significant influence on delta flux. Furthermore, both the delta flux and the ABI value in patients with microalbuminuria were lower than in patients with normoalbuminuria (P <.05). The results suggest that BPS increases the skin blood flow of the toe of patients with type 2 diabetes and that the increased flow is independently influenced by the value of the ABI and the plasma TM levels; in addition, microalbuminuria is associated with the impairment of vasodilation in the feet in response to BPS.

Adult↗
PubMed2001

Relationship between plasma soluble thrombomodulin levels and insulin resistance syndrome in type 2 diabetes: a comparison with von Willebrand factor.

Endothelial dysfunction plays a pivotal role in the initial stage of atherosclerosis. Insulin resistance is associated with accelerated atherosclerosis, especially coronary heart disease. To elucidate the relationship between endothelial dysfunction and insulin resistance or insulin resistance syndrome in patients with type 2 diabetes, we investigated the correlation between plasma soluble thrombomodulin (TM) and von Willebrand factor (vWF), measures of endothelial dysfunction, and the degree of insulin resistance evaluated by homeostasis assessment models of insulin resistance (HOMA-IR), or variables of insulin resistance syndrome. We studied 53 patients with type 2 diabetes, 23 treated with diet alone and 30 treated with sulfonylureas, who had normal renal function. The plasma soluble TM concentrations were highly correlated with HOMA-IR (r=0.64, p<0.0001), the plasma insulin (r=0.72, p<0.0001), the systolic blood pressure (r=0.45, p=0.0005), and the plasma fibrinogen (r=0.43, p=0.0018), while they were inversely correlated with the serum HDL cholesterol concentrations (r=-0.27, p=0.0344). The plasma vWF concentrations were positively correlated with HOMA-IR (r=0.35, p=0.0151) and the plasma fibrinogen (r=0.32, p=0.0203), but not with the plasma insulin, the systolic blood pressure or the HDL cholesterol concentrations. Furthermore, plasma TM, but not vWF, was positively correlated with total number of variables of insulin resistance syndrome (r=0.45, p=0.0005). These results indicate that endothelial dysfunction may be associated with the pathogenesis of insulin resistance syndrome as well as insulin resistance, and that the plasma TM might reflect endothelial damage better than the plasma vWF in the state of insulin resistance in patients with type 2 diabetes.

Adult↗
PubMed2001

Clinical features of a polymorphism of the beta3-adrenergic receptor gene in patients with type 2 diabetes mellitus--a study using a pin-point sequencing method.

UNLABELLED: The human beta(3)-adrenergic receptor (beta(3)AR) is expressed specifically in adipose tissues, and its activation is activated in brown adipose tissues during thermogenesis and in white adipose tissues during lipolysis. We investigated the relationship between a polymorphism of the beta(3)AR gene and the clinical features of type 2 diabetes mellitus. Studies were conducted in 30 type 2 diabetic patients (15 males and 15 females). Analysis of polymorphisms of the beta(3)AR gene was performed by a pin-point sequencing method using the hair of the subjects. Preperitoneal (P-fat) and subcutaneous fat (S-fat) levels were determined by ultrasonography. We found a Trp(64)Arg allele of the beta(3)AR gene in the hair of 27% of all patients. The patients with this mutation showed a significantly younger onset-age of diabetes than those of the wild type. The body mass index, serum GPT levels, fasting immunoreactive insulin (IRI) and daily urinary C-peptide reaction (CPR) in the mutation group were markedly higher than in the wild type group. The P-fat, serum cholesterol and leptin concentrations tended to be higher in the mutation group. Patients in the mutation group had a significantly higher prevalence of hypertension (80%) compared with those in the wild type group (20%). CONCLUSIONS: The present results suggest that the clinical features of diabetic patients with a missense mutation in the beta(3)AR gene are substantially distinct from those of the wild type patients. These specific features include obesity, hyperinsulinemia, hypertension, and an increase in preperitoneal fat.

Adipose Tissue↗
PubMed2001

Localization, accumulation, and antifungal activity of chitinases in rye (Secale cereale) seed.

In order to understand a physiological role of chitinases in rye, the localization and accumulation of rye seed chitinase-a and -c (RSC-a and -c) in the seeds were studied by immunochemical methods. An antiserum specific to the chitin-binding domain (CB-domain), which is an N-terminal part of RSC-a, and an antiserum specific to the catalytic region of RSC-a and RSC-c were used. An immunoblot analysis detected both RSC-a and RSC-c in the endosperm of the rye seed. Immunohistochemical staining indicated that RSC-a was localized in only the aleurone cells, whereas RSC-c existed at least in the starchy endosperm and was also likely to exist in the aleurone cells. It was found by ELISA and an immunoblot analysis that RSC-a and -c accumulated in the seed during the later stage of development. Both chitinases and the Cat-domain exhibited antifungal activity toward Trichoderma species, while the CB-domain did not. Observation of the inhibition of hyphal growth of the T. species suggests that the two chitinases acted in different ways.

Antifungal Agents↗