Biomedical subjects

Y Aso

Publications and source records attributed to Y Aso.

At least 37 records · Page 2Linked to original sources

PubMed2001

Thermally induced changes of lipoate acetyltransferase inner core isolated from the Bacillus stearothermophilus pyruvate dehydrogenase complex.

Incubation at 70 degrees C converted the Bacillus stearothermophilus lipoate acetyltransferase inner core into an unidentified active molecular form, X, yielding an inactive aggregate. The core and X showed similar thermostabilities, but they were different in the recovery of enzyme activity after incubation with 1.2-2.0 M guanidine hydrochloride and its subsequent removal; the core was hardly recovered, but X was well recovered.

Acetyltransferases↗

PubMed2000

Synthesis and spectroscopic properties of

The title compound has been synthesized as the first oligothiophenophane that has the typical stacking structure of a layered cyclophane and can behave as an ideal pi-dimer model.

Journal Article↗

PubMed2000

International Consultation on Urological Diseases: a decade of progress.

The International Consultation on Urological Diseases (ICUD), under the cosponsorship of the World Health Organization (WHO), the International Society of Urology (SIU), and the International Union Against Cancer (UICC), is active in the organization of global consultations on urological diseases. The major urological associations from the five continents (the American Urological Association (AUA), the Urological Association of Asia (UAA), the Confederation Americana Urologia (CAU), and the European Association of Urology (EAU)), together with societies with expertise in specific programs such as the International Continence Society, the International Society for Impotence Research, the International Prostate Health Council, the American Cancer Society, the International Union Against Cancer, and the European Organization for Research and Treatment of Cancer, came together in the late 1980s on the basis of their proven record in organizing successful international meetings on urological cancer to initiate the concept of the ICUD. At the suggestion of the WHO, a First International Consultation on Benign Prostatic Hypertrophy (BPH) was organized in 1991, not only to provide recommendations to medical practitioners but also to define and plan future research on the subject. The formula, based on global multiprofessional collaboration and expertise, exceeded expectations, and other consultations were to follow, e.g., on prostate cancer, incontinence, erectile dysfunctions, and nosocomial infections. In 1994 it became necessary to establish a legal nongovernmental organization to foster the goals of the ICUD, essentially for the creation of awareness, knowledge, and recommendations on the diagnosis and treatment of urological diseases.

Humans↗

PubMed2000

Relationship between the crystallization rates of amorphous nifedipine, phenobarbital, and flopropione, and their molecular mobility as measured by their enthalpy relaxation and (1)H NMR relaxation times.

Isothermal crystallization of amorphous nifedipine, phenobarbital, and flopropione was studied at temperatures above and below their glass transition temperatures (T(g)). A sharp decrease in the crystallization rate with decreasing temperature was observed for phenobarbital and flopropione, such that no crystallization was observed at temperatures 20-30 degrees C lower than their T(g) within ordinary experimental time periods. In contrast, the crystallization rate of nifedipine decreased moderately with decreasing temperature, and considerable crystallization was observed at 40 degrees C below its T(g) within 4 months. The molecular mobility of these amorphous drugs was assessed by enthalpy relaxation and (1)H-NMR relaxation measurements. The enthalpy relaxation time of nifedipine was smaller than that of phenobarbital or flopropinone at the same T - T(g) values, suggesting higher molecular mobility of nifedipine. The spin-lattice relaxation time in the rotating frame (T(1rho)) decreased markedly at temperature above T(g). The slope of the Arrhenius type plot of the T(1rho) for nifedipine protons changed at about 10 degrees C below the T(g), whereas the slope for phenobarbital protons became discontinuous at about 10 degrees C above the T(g). Even at temperatures below its T(g), the spin-spin relaxation process of nifedipine could be described by the sum of its Gaussian relaxation, which is characteristic of solid protons, and its Lorentzian relaxation, which is characteristic of protons with higher mobility. In contrast, no Lorentzian relaxation was observed for phenobarbital or flopropione at temperatures below their T(g). These results also suggest that nifedipine has higher molecular mobility than phenobarbital and flopropione at temperatures below T(g). The faster crystallization of nifedipine than that of phenobarbital or flopropione observed at temperatures below its T(g) may be partly ascribed to its higher molecular mobility at these temperatures.

Crystallization↗

PubMed2000

International Society of Urology in the twenty-first century.

The International Society of Urology (SIU) has revised its by-laws and reformed its system to adjust to the changes of the new millennium. The most important role the SIU can play at present is to fill the gap between developing and developed countries, which can be accomplished through the sister center program. After having achieved this primary aim, international cooperative work at a higher level can be considered through establishment of various institutes to bolster the high standard of world urology.

International Cooperation↗

PubMed2000

Serum concentrations of advanced glycation endproducts are associated with the development of atherosclerosis as well as diabetic microangiopathy in patients with type 2 diabetes.

We measured serum concentrations of advanced glycation endproducts (AGEs) in patients with type 2 diabetes, to elucidate the mechanisms underlying the elevated serum concentrations of AGEs and to clarify the relationship between serum AGE concentrations and the development of microangiopathy and macroangiopathy. Serum AGEs were significantly higher in diabetic patients than in age-matched control subjects (p < 0.0001). In diabetic patients, serum AGEs were positively correlated with HbAlc (r = 0.47, p < 0.0001), urinary albumin excretion (UAE) (r = 0.42, p < 0.0001), diabetes duration (r = 0.31, p = 0.0030), and fasting plasma glucose (r = 0.34, p = 0.0010). Multiple regression analysis disclosed that only the HbAlc and UAE levels independently correlated with serum AGE levels. Serum AGEs in diabetic patients with progressive retinopathy and overt nephropathy were significantly higher than in those with less severe retinopathy and nephropathy. Serum AGEs were significantly higher in the diabetic patients with coronary heart disease (CHD) than in those without CHD. These results suggest that the HbAlc and UAE levels are independent risk factors for increased serum AGE concentrations in type 2 diabetic patients, and that higher serum AGE concentrations are associated with increased severity of diabetic retinopathy and nephropathy. Serum AGE concentrations may be a useful marker not only for the severity of diabetic microangiopathy but also for the development of CHD in patients with type 2 diabetes mellitus.

Aged↗

PubMed2000

Relationship between soluble thrombomodulin in plasma and coagulation or fibrinolysis in type 2 diabetes.

Serum concentration of soluble thrombomodulin (TM) is thought to be a marker for endothelial damage. Although several studies have reported that serum TM concentrations are increased in patients with diabetes mellitus, there is little information on the physiological function of soluble TM in human plasma. To evaluate the relationship of soluble TM in plasma between coagulation and/or fibrinolysis system in patients with diabetes, we measured plasma soluble TM, protein C activity (a natural anticoagulant induced by thrombin-TM complex), prothrombin F1+2 (a direct marker of thrombin generation), and plasmin-alpha 2-antiplasmin complex (PAP) and D dimer (measures of fibrinolytic activity) in 55 patients with type 2 diabetes mellitus. The plasma concentrations of soluble TM (P<0.01), protein C activity (P<0.01), prothrombin F1+2 (P<0.05), PAP (P<0.001) and D dimer (P<0.001) were significantly higher in the diabetic patients than the 48 age-matched control subjects. The plasma concentrations of TM and PAP were obviously increased in patients with diabetic nephropathy. In the diabetic patients, the plasma concentrations of soluble TM were inversely correlated with the protein C activity (r=-0.43, P<0.005), and were positively correlated with the plasma concentrations of prothrombin F1+2 (r=0.63, P<0.0001) and the plasma PAP concentrations (r=0.30, P<0.05). The present study demonstrated that both coagulation and fibrinolysis are enhanced concomitantly in patients with type 2 diabetes mellitus, and that an increase in plasma concentration of soluble TM is associated not only with hypercoagulability but also with enhanced fibrinolysis in diabetic patients.

Adult↗

PubMed2000

Serum levels of carboxy-terminal propeptide of human type I procollagen are an indicator for the progression of diabetic nephropathy in patients with type 2 diabetes mellitus.

The finding that glomerular mesangial cells produce human type I collagen suggests that the serum levels of carboxy-terminal propeptide of human type I procollagen (P1CP) may reflect the severity of diabetic nephropathy. We therefore investigated the relationship between serum P1CP levels and the extent of diabetic complications in 100 patients (46 males and 54 females) with Type 2 diabetes and in 64 healthy subjects. Serum P1CP was determined by radioimmunoassay. In diabetes, we defined P1CP levels less than 142 ng/ml as a normal P1CP group (group A), whereas we defined them as equal to or greater than 142 ng/ml as a high P1CP group (group B). The diabetic patients had significantly elevated serum P1CP levels compared with the controls. The prevalence of hypertension, proliferative diabetic retinopathy or macroalbuminuria was significantly higher in group B than in group A. Serum P1CP levels showed a significant positive correlation with urinary albumin excretion, but not with fasting blood glucose, glycosylated hemoglobin A(1c) or serum osteocalcin. Macroalbuminuric patients showed significantly higher P1CP levels than the normoalbuminuric patients. In patients in the absence of diabetic nephropathy, no significant differences of P1CP levels were found among the severity of diabetic retinopathy. The present results suggest that serum P1CP levels reflect the progression of diabetic nephropathy in patients with Type 2 diabetes.

Biomarkers↗

PubMed2000

Temperature dependence of bimolecular reactions associated with molecular mobility in lyophilized formulations.

PURPOSE: We studied the temperature dependence of acetyl transfer between aspirin and sulfadiazine, a bimolecular reaction, in lyophilized formulations at temperatures near the glass transition temperature (Tg) and NMR relaxation-based critical mobility temperature (Tmc), to further understand the effect of molecular mobility on chemical degradation rates in solid pharmaceutical formulations. The temperature dependence of the hydrolysis rates of aspirin and cephalothin in lyophilized formulations was also studied as a model of bimolecular reactions in which water is a reactant. METHODS: Degradation of lyophilized aspirin-sulfadiazine formulations containing dextran and various amounts of water at temperatures ranging from 1 degrees C to 80 degrees C was analyzed by HPLC. The degradation of cephalothin in lyophilized formulations containing dextran and methylcellulose was also analyzed at temperatures ranging from 10 degrees C to 70 degrees C. RESULTS: Acetyl transfer in lyophilized aspirin--sulfadiazine formulations containing dextran exhibited a temperature dependence with a distinct break around Tmc, which may be ascribed to a change in the translational mobility of aspirin and sulfadiazine molecules. The hydrolysis of aspirin and cephalothin in lyophilized formulations, which is also a bimolecular reaction, did not show a distinct break, suggesting that water diffusion is not rate-limiting. CONCLUSIONS: The diffusion barrier of water molecules in lyophilized formulations appears to be smaller than the activational barrier of the hydrolysis of aspirin and cephalothin based on the results of this study that the temperature dependence of the hydrolysis rate is almost linear regardless of Tmc and Tg. On the other hand, the diffusion barrier of aspirin and sulfadiazine molecules appears to be comparable to the activational barrier of the acetyl transfer reaction between these compounds, resulting in nonlinear temperature dependence.

Anti-Infective Agents↗

PubMed2000

Thermographic measurement of skin temperature recovery time of extremities in patients with type 2 diabetes mellitus.

To elucidate the relationship between the recovery of skin temperature in an extremity after exposure to cold water and various factors associated with diabetes, we measured skin temperature in type2 diabetic patients (N=61) and control subjects (N=16). A thermo-tracer was used in thermographic measurements. The right third toe of each subject was immersed in cold water at 0 degrees C for 10 sec. Rt represents the recovery rate of skin temperature at t min after exposure. Rt was significantly reduced in the diabetic patients every 5 min in the 20 min period following exposure compared with control subjects. The diabetic patients group exhibited a significantly positive correlation between R20 and the ankle-brachial index. R20 in the diabetic patients showed a significantly positive correlation with the reduction in systolic blood pressure at the arm observed in Schellong's test. In addition, R20 showed a significantly negative correlation with plasma levels of fibrinogen and plasminogen activator inhibitor-1. However, the severity of diabetic retinopathy and nephropathy was not significantly related to R20 in the diabetic patients. The present data indicate that the recovery of skin temperature after immersion in cold water was markedly reduced in patients with type 2 diabetes mellitus as compared with healthy control subjects. Peripheral arteriosclerosis, impaired sympathetic nerve function and the activation of the blood coagulation system may all contribute to this reduced recovery of skin temperature.

Analysis of Variance↗

PubMed2000

Early results of LH-RH agonist treatment with or without chlormadinone acetate for hormone therapy of naive localized or locally advanced prostate cancer: a prospective and randomized study. The Prostate Cancer Study Group.

BACKGROUND: The majority of patients with localized and some cases of locally advanced prostate cancer undergo radical prostatectomy. However, radical prostatectomy cannot always be selected for those patients. In this situation, primary hormone therapy is an alternative treatment option. We have designed a prospective randomized study of the effects of primary hormone therapy for such patients. METHODS: A total of 151 patients with T1b, T1c, T2a, T2b or T3a prostate cancer who were not scheduled for radical prostatectomy were enrolled into this study. Patients were randomly allocated into two groups; Group I received luteinizing hormone-releasing hormone (LH-RH) agonist monotherapy (leuprorelin acetate depot, 3.75 mg monthly) and Group II received LH-RH agonist in combination with chlormadinone acetate (100 mg/day). Effects on serum prostate-specific antigen level, progression-free survival and survival were observed for 2 years. RESULTS: The reasons why radical prostatectomy was not scheduled were poor risk for surgery (38%), patient's wish (32%) and physician's recommendation (30%). After 12 weeks of treatment, 49% of the patients in both groups showed a complete response (CR). Of the patients showing a partial response (PR) after 12 weeks of treatment, 25% in Group I and 52% in Group II improved to CR 1 year later (p<0.05). Group II showed a longer progression-free survival (p <0.05). Progression-free survival rates were 62% (Group I) and 91% (Group II) in T2b patients and 43% (Group I) and 73% (Group II) in T3 patients. Only one patient in each group died from prostate cancer. CONCLUSIONS: Early primary hormone therapy is a reasonable treatment option for localized or locally advanced prostate cancer patients if radical prostatectomy was not scheduled. Chlormadinone acetate showed an additive effect with LH-RH agonist, at least in 2 years' observation.

Aged↗

PubMed2000

Effect of polymer excipients on the enzyme activity of lyophilized bilirubin oxidase and beta-galactosidase formulations.

The effects of excipients on the protein stability during lyophilization as well as the storage stability of lyophilized bilirubin oxidase (BO) and beta-galactosidase (GA) formulations were studied using four polymer excipients: dextran, polyvinylalcohol (PVA), poly(acrylic acid) (PAA), and alpha, beta-poly(N-hydroxyethyl)-L-aspartamide (PHEA). Denaturation of BO and GA during lyophilization largely depended on the excipient used. Dextran appeared to cause severe damage to proteins, whereas PHEA protected proteins effectively from denaturation. Storage stability of BO and GA formulations also depended on the excipients, such that the formulations containing dextran and PAA were relatively unstable. Storage stability was improved by absorption of a small amount of water for all the formulations studied. Absorption of a larger amount of water, however, decreased the storage stability of the formulations containing PVA, PAA or PHEA. In contrast, the storage stability of formulations containing dextran did not decrease noticeably with increasing water. This may be because formulations containing dextran have a higher glass transition temperature than formulations containing PVA, PAA or PHEA when a large amount of water is absorbed.

Acrylic Resins↗

PubMed2000

Expression of prophenoloxidase mRNA during silkworm hemocyte development.

Two clones encoding different prophenoloxidase isoforms were amplified by polymerase chain reaction of RNA from the hemocytes of an experimental strain of Bombyx mori. The nucleotide sequences of the clones and the deduced amino acid sequences were confirmed to be nearly identical to those of the orthologous clones previously obtained from a commercial race of B. mori. Northern blot hybridization using these clones as probes demonstrated that the prophenoloxidase mRNA in the hemocytes is expressed in a stage-specific manner during the final larval instar and pupal stage, showing a peak one day before pupation in males and on the day of pupation in females. A sexual difference was also observed when the content of prophenoloxidase protein in the hemolymph (including hemocytes) was measured by an enzyme-linked immunosorbent assay.

Amino Acid Sequence↗

PubMed2000

Thermally induced disintegration of the Bacillus stearothermophilus dihydrolipoamide dehydrogenase.

Upon heat treatment of the pyruvate dehydrogenase complex from Bacillus stearothermophilus, the most thermostable component is a dihydrolipoamide dehydrogenase (E3c). To understand this stability, the thermal disintegration of E3 dissociated from the complex (E3d) was examined, comparing with that of E3c. Judging from residual activity and inactivation rate, E3d was less thermostable than E3c; E3d and E3c lost half of their original activities upon incubations for 30 min at 79 degrees C and 90 degrees C, respectively. Heat treatment of E3d raised the fluorescence intensities of Trp residue, intrinsic FAD, and extrinsic 8-anilinonaphthalene-1-sulfonate. E3d lost FAD, and inactive E3d polypeptides were aggregated. The sulfonate bound to the aggregate became notably fluorescent. The thermal disintegration of E3d was speculated to be a consecutive reaction that was different from the concurrent disintegration reaction of the complex. Some interactions with other component polypeptides was suggested to improve the thermostability of E3c.

Chromatography, Gel↗

PubMed2000

Estrogen markedly increases LDL-receptor activity in hypercholesterolemic patients.

We investigated the change in low-density lipoprotein receptor activity following the administration of estrogen to patients with hypercholesterolemia (HC). Studies were conducted in 16 patients with HC (total cholesterol (TC)>220 mg/dL) and 133 healthy control subjects. LDL-R activity was measured by fluorocytometry. Three of sixteen patients with HC showed low LDL-R activity below 80% together with extremely high serum levels of TC and LDL cholesterol (LDL-C). LDL-R activity showed an inverse correlation with serum levels of TC and LDL-C (p<0.05, respectively). Two women with initially low LDL-R activity who showed a marked increase in LDL-R activity exhibited a normalized activity at four and eight weeks after estriol administration, proportional to the reduction in serum levels of TC and LDL-C. One man with an initially extremely low LDL-R activity showed no abnormality at the sites of exons 7, 14, 17 and intron 12 by the PCR-DGGE method, which are common sites for point-mutations of LDL-R among Japanese patients with HC. Estrogen reduced serum levels of TC and LDL-C in patients with HC, at least in part, via an increase in the LDL-R activity of patients with HC and an initially low LDL-R activity.

Adult↗

PubMed1999

Large-Scale Mapping Observations of the C i (3P1-3P0) and CO (J = 3-2) Lines toward the Orion A Molecular Cloud.

Large-scale mapping observations of the 3P1-3P0 fine-structure transition of atomic carbon (C i, 492 GHz) and the J=3-2 transition of CO (346 GHz) toward the Orion A molecular cloud have been carried out with the Mount Fuji submillimeter-wave telescope. The observations cover 9 deg2 and include the Orion Nebula M42 and the L1641 dark cloud complex. The C i emission extends over almost the entire region of the Orion A cloud and is surprisingly similar to that of 13CO (J=1-0). The CO (J=3-2) emission shows a more featureless and extended distribution than C i. The C i/CO (J=3-2) integrated intensity ratio shows a spatial gradient running from the north (0.10) to the south (1.2) of the Orion A cloud, which we interpret as a consequence of the temperature gradient. On the other hand, the C i/13CO (J=1-0) intensity ratio shows no systematic gradient. We have found a good correlation between the C i and 13CO (J=1-0) intensities over the Orion A cloud. This result is discussed on the basis of photodissociation region models.

Journal Article↗

PubMed1999

The effect of excipients on the molecular mobility of lyophilized formulations, as measured by glass transition temperature and NMR relaxation-based critical mobility temperature.

PURPOSE: The dependence of the molecular mobility of lyophilized formulations on pharmaceutical polymer excipients was studied. Molecular mobility as determined by NMR relaxation-based critical temperature of molecular mobility (Tmc) and glass transition temperature (Tg) is discussed in relation to the plasticizing effect of water in formulations. METHODS: The Tmc and Tg of lyophilized gamma-globulin formulations containing 6 different polymer excipients such as dextran, polyvinylpyrrolidone (PVP) and methylcellulose (MC) was determined by NMR and DSC. The molecular mobility of water in the formulations was determined by proton NMR and dielectric relaxation spectrometry (DRS). RESULTS: Tmc varied with polymer excipients. Tmc increased as the ratio of bound water to mobile water increased and as the molecular mobility of mobile water decreased. The formulation containing MC exhibited a lower Tmc than the formulation containing dextran because of the smaller ratio of bound water and the higher molecular mobility of mobile water. The Tmc of the formulation containing PVP was higher than that expected from the higher T2 values of water because of the lower molecular mobility of mobile water regardless of the higher ratio of mobile water. The Tmc of these lyophilized formulations was higher than their T(g) by 23 degrees C to 34 degrees C, indicating that the formulations became a NMR-detected microscopically liquidized state below their T(g). CONCLUSIONS: The quantity and the molecular mobility of mobile water in lyophilized formulations can be considered to affect the T(mc) of lyophilized formulations, which in turn governs their stability.

Calorimetry, Differential Scanning↗

PubMed1999

Molecular mobility of protein in lyophilized formulations linked to the molecular mobility of polymer excipients, as determined by high resolution 13C solid-state NMR.

PURPOSE: The mobility of protein molecules in lyophilized protein formulations was compared with that of excipient molecules based on the spin-lattice relaxation time (T1) of each molecule determined by high resolution 13C solid-state NMR. The relationship between molecular mobility and protein stability is discussed. METHODS: Protein aggregation of lyophilized bovine serum gamma-globulin (BGG) formulation containing dextran was measured by size exclusion chromatography. The T1 of the BGG carbonyl carbon and dextran methin carbon in the formulation was determined by high resolution 13C NMR, and subsequently used to calculate the correlation time (tauc) of each carbon. The spin-spin relaxation time (T2) of BGG and dextran protons was measured by pulsed NMR spectrometry, and the critical temperature of appearance of Lorentzian relaxation due to liquid BGG and dextran protons (Tmc) was determined. RESULTS: The tauc of dextran methin carbon in BGG-dextran formulations exhibited a linear temperature dependence according to the Adam-Gibbs-Vogel equation at lower temperatures, and a nonlinear temperature dependence described by the Vogel-Tamman-Fulcher equation at higher temperatures. The temperature at which molecular motion of dextran changed was consistent with the Tmc. The tauc of BGG carbonyl carbon exhibited a similar temperature dependence to the tauc of the dextran methin carbon and substantially decreased at temperatures above Tmc in the presence of dextran. The temperature dependence of BGG aggregation could be described by the Williams-Landel-Ferry equation even at temperatures 20 degrees C lower than Tmc. CONCLUSIONS: High resolution 13C solid-state NMR indicated that the molecular motion of BGG was enhanced above Tmc in association with the increased global segmental motion of dextran molecules.

Algorithms↗