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S Yoshioka

Publications and source records attributed to S Yoshioka.

At least 109 records · Page 6Linked to original sources
PubMed1998

[Assessment of stability variation among batches, packaging, and formulations--application of matrixing and bracketing].

Assessment of shelf-life equivalence among batches, packaging or formulations of pharmaceutical products, which was based on the range of shelf-life estimates, was proposed as an alternative method to an analysis of variance (ANOVA). The power of this analysis was not significantly affected by assay error, whereas that of ANOVA decreased markedly as assay error increased. Thus, ANOVA exhibites a tendency to overlook the stability variation from stability data of a larger assay error, but this is not the case for the proposed method.

Analysis of Variance↗
PubMed1998

Mean regional cerebral blood flow images of normal subjects using technetium-99m-HMPAO by automated image registration.

UNLABELLED: The purpose of this study was twofold: to calculate relative uptake values for 99mTc-HMPAO in various regions of the normal brain after alignment and registration to a standard shape and size, and to validate the automated image registration (AIR) program for SPECT-to-SPECT transformation. METHODS: Thirty subjects took part in this study. Technetium-99m-HMPAO brain SPECT and x-ray-CT scans were acquired. SPECT images were normalized to an average activity of 100 counts/pixel. Intersubject accuracy was evaluated on brain images of 17 normal subjects (mean age = 64.9 +/- 8.7 yr). These images were aligned and registered to a standard size and shape with the help of AIR. Realigned images were overlaid on reference images to determine the overlap areas. Intrasubject accuracy was evaluated by realigning 20 degree rotated brain images with an index calculated as: overlap area/(overlap area + nonoverlap area). Anatomical variability between realigned target and reference images was evaluated by measurements on corresponding x-ray-CT scans, realigned using transformations that were established by the SPECT images. Realigned brain SPECT images of 30 normal subjects (mean age = 50.7 +/- 18.7 yr), including those subjects examined in the accuracy validation study, were used to generate mean and s.d. images. Images based on the mean value of each voxel (n = 30) were compared with other mean images prepared by the human brain atlas (HBA) standardization technique on a voxel-by-voxel basis to generate T maps. RESULTS: Accuracy indices were 0.98 +/- 0.006 and 0.99 +/- 0.002 for the intersubject and intrasubject evaluations, respectively. The maximum anatomical variability was 4.7 mm after realignment. Paired Student's t-test comparisons of mean HBA and AIR images revealed statistically significant differences for the deep white matter, pons and occipito-temporal regions. These differences could be explained by variation in the population being studied and the protocol for data handling by AIR and HBA. CONCLUSION: AIR aligns and registers brain SPECT images with acceptable accuracy, without the necessity of MRI or x-ray-CT scans.

Brain↗
PubMed1998

[Clinical usefulness of 201Tl-chloride scintigraphy for the evaluation of metastatic bone lesions].

201Tl-Chloride scintigraphy (early and delayed images) was performed in 40 patients with suspected metastatic bone lesions. The sensitivity and specificity of 201Tl scanning for detecting metastatic bone lesions were 66.7% and 77.4%, respectively. The uptake ratio of 201Tl per voxel of the lesions to the normal site was significantly different between the metastatic bone lesion and benign lesions. In 20 sites of 15 patients, 201Tl-Chloride scintigraphy was performed before and after radio- or radiothermotherapy. There was a significant difference in the mean uptake ratios in the early and delayed scans between before and after therapy. The mechanism of intracellular uptake of 201Tl is considered to be one of active transport, which might make 201Tl an accurate indicator of the viability of tumor cells and metabolic activity as long as there is sufficient blood flow to prompty transport 201Tl to tumor cells. Thus it would seem that decreased uptake of 201Tl and change in retention index after therapy depends partially on tumor blood flow. In conclusion, 201Tl-Chloride scintigraphy is very useful not only for clinically detecting metastatic bone lesions but also for assessing the therapeutic effects.

Aged↗
PubMed1998

Relationship of xenogeneic microchimerism to graft outcome in hamster-to-rat lung xenotransplantation.

BACKGROUND: In spite of the progress in allogeneic microchimerism research, few reports have dealt with the biologic relevance of xenogeneic microchimerism after organ xenotransplantation. These experiments were designed to analyze the development of xenogeneic microchimerism and its relationship to graft outcome in hamster-to-rat lung xenotransplantation. METHODS: Golden Syrian hamsters were the donors and Lewis rats the recipients of xenogeneic lung transplantation. Animals were divided into three groups: group 1 were untreated; group 2 received cyclophosphamide (10 mg/kg/day for 6 days) and a short course of FK506 (2 mg/kg/day for 8 days); and group 3 were treated with cyclophosphamide and a long course of FK506 (2 mg/kg/day for 8 days, 1 mg/kg/day for 23 days, and then 0.5 mg/kg/day continuously). Xenogeneic microchimerisms were evaluated by use of polymerase chain reaction with primers specific for the hamster hypoxanthine phosphoribosyl-transferase gene. RESULTS: The median graft survival times for groups 1, 2, and 3 were 3 days (n = 6), 22 days (n = 7), and 96.5 days (n = 6), respectively. In groups 1 and 2, the incidence of microchimerisms declined in parallel with the progression of rejection. In group 3, it changed dynamically, initially declining, then progressively increasing and finally disappearing. CONCLUSIONS: In the short-term graft survivors, xenogeneic microchimerism in the peripheral blood was closely related to graft outcome. However, it showed dynamic changes and finally disappeared in long-term graft survivors, and the incidence of microchimerism at a single time point did not reflect the donor-recipient immunologic status.

Animals↗
PubMed1998

Thoracoscopic microwave coagulation therapy for hepatocellular carcinoma.

Thoracoscopic microwave coagulation therapy (MCT) is a new therapeutic approach for hepatocellular carcinoma (HCC) in segments VII and VIII, which allows minimal access to the tumor and complete tumor ablation. In this study, four patients with HCC in segments VII and VIII underwent thoracoscopic MCT as a less invasive therapeutic option due to advanced liver cirrhosis and/or severe complications. Tumor sizes ranged from 15 to 30 mm in diameter and the tumors were well differentiated in 2 patients, moderately in one and poorly in one patient. Microwave irradiation was performed at an 80 W output with a 60-sec duration via a thoracoscopic route and the total duration ranged from 4 to 24 min (mean: 17 min). Patients recovered rapidly to preoperative conditions and no mortality was occurred. Complications were observed in one patient, including pleural effusion and fever elevation, but were cured conservatively. Postoperative computed tomography (CT) showed complete tumor ablation with a cancer-free margin, which is thought to be equivalent to a limited hepatic resection. This preliminary study suggests that thoracoscopic MCT might be a new, less invasive option providing a cure for HCC in segments VII and VIII in patients with advanced liver cirrhosis and severe complications.

Aged↗
PubMed1997

Identification of open reading frames in Schizosaccharomyces pombe cDNAs.

A total of 214 non-overlapping cDNA clones from Schizosaccharomyces pombe were selected and completely sequenced. The clones not previously reported were divided into the following three groups: 1) homologous to Saccharomyces cerevisiae genes (139 clones); 2) homologous to genes from other organisms but not to those from Sac. cerevisiae (4 clones); and 3) no similar sequences (40 clones). Among the 31 sequences identical to those in the public databases, 4 genes have regions corresponding to introns. Protein sequences which had homologs both in budding yeast and mammals were compared with those from Sac. cerevisiae and mammals. The search revealed that the evolutionary distances among these species are similar at least with genes of this category.

Amino Acid Sequence↗
PubMed1997

Isolation and partial characterization of bacteriocins produced by Lactobacillus gasseri JCM 2124.

Four antibacterially active peptides (B1 to B4) were purified from the culture broth of L. gasseri JCM 2124. The B2 peptide (gassericin B2) was determined to be 4400 Da by mass spectrometry and partially sequenced. Gassericin B2 did not show any sequence similarities to other known bacteriocins. The B1 and B3 peptides shared identical sequences with two peptides of a two-component bacteriocin from Lactobacillus acidophilus. However, synergistic activity upon complementation of B1 and B3 was not observed. Based on amino acid sequencing and molecular mass, it is suggested that B1 and B4 peptides were derived from B3 (gassericin B3).

Amino Acid Sequence↗
PubMed1997

Acute effect of troglitazone on glucose metabolism in the absence or presence of insulin in perfused rat hindlimb.

Troglitazone (CS-045) is a new type of antidiabetic agent that decreases plasma glucose by enhancing insulin action in insulin-resistant diabetic animals and non-insulin-dependent diabetes mellitus (NIDDM) patients. To examine the direct effect of troglitazone on glucose metabolism and insulin action in skeletal muscle, we infused troglitazone solution into perfused rat hindlimbs in the presence of 6 mmol/L glucose and in the absence or presence of insulin. In the absence of insulin, even 50 mumol/L troglitazone did not elicit glucose uptake. Troglitazone did increase lactate and pyruvate release at concentrations of 20 mumol/L and higher; however, it decreased the ratio of lactate to pyruvate (L/P ratio) and increased oxygen consumption at concentrations higher than 5 and 20 mumol/L, respectively. In hindlimb muscle, 20 mumol/L troglitazone decreased glycogen content without changing fructose 2,6-bisphosphate (F2,6P2) content in the absence of insulin. Insulin infusion with 250 microU/mL obtained half-maximal effects, causing a 2.8-fold increase in glucose uptake and a 1.5-fold increase in lactate and pyruvate release. When 20 mumol/L troglitazone was infused for 30 minutes together with 250 microU/mL insulin, insulin-induced glucose uptake significantly increased 30 minutes after troglitazone infusion, and this increase was further augmented after withdrawal of troglitazone. In insulin plus troglitazone infusion at 30 minutes after troglitazone removal, glycogen content in hindlimb muscle was significantly decreased compared with that obtained with insulin infusion alone. In summary, in the absence of insulin, troglitazone does not elicit glucose uptake, but causes an increase in glycolysis accompanied by a decrease in muscle glycogen content and L/P ratio and an increase in oxygen consumption. In the presence of insulin, troglitazone increases insulin-induced glucose uptake, and this increase is further augmented after troglitazone removal. Addition of troglitazone to insulin infusion decreased the glycogen content in hindlimb muscle. This decrease in muscle glycogen content may trigger an enhancement of insulin-induced glucose uptake similar to that observed during muscle contraction or epinephrine treatment.

Animals↗
PubMed1997

Softening temperature of lyophilized bovine serum albumin and gamma-globulin as measured by spin-spin relaxation time of protein protons.

We investigated the usefulness of the spin-spin relaxation time (T2) of protein protons as a probe for evaluating the molecular flexibility of freeze-dried protein formulations. It is proposed that the microscopic softening temperature determined from changes in the T2 of protein protons (Ts(T2)) is an important characteristic of freeze-dried protein formulations, the glass transition temperature (Tg) of which is generally difficult to determine by differential scanning calorimetry. We determined the molecular flexibility of lyophilized bovine serum albumin (BSA) and bovine gamma-globulin (BGG) by measuring the T2 of protein and water protons as well as the spin-lattice relaxation time (T1) of the latter as a function of temperature. The flexibility of freeze-dried BSA and BGG cakes markedly varied at temperatures above and below the Ts(T2), affecting the stability of the proteins. The denaturation and subsequent aggregation of lyophilized BSA and BGG cakes with a relatively high water content was enhanced in the softened state at temperatures above the Ts(T2). Lyophilized cakes with an extremely low water content were significantly denatured, even in the unsoftened state at temperatures below the Ts(T2), probably due to the thermodynamically unstable structures of protein molecules generated by a loss of structural water.

Chromatography, Gel↗
PubMed1997

Dependence of the molecular mobility and protein stability of freeze-dried gamma-globulin formulations on the molecular weight of dextran.

PURPOSE: The effect of the molecular weight of dextran on the molecular mobility and protein stability of freeze-dried serum gamma-globulin (BGG) formulations was studied. The stabilizing effect of higher molecular weight dextran is discussed in relation to the molecular mobility of the formulations. METHODS: The molecular mobility of freeze-dried BGG formulations containing dextrans of various molecular weights was determined based on the free induction decay of dextran and water protons measured by proton NMR. The protein stability of the formulations was determined at temperatures ranging from 20 to 70 degrees C by size exclusion chromatography. RESULTS: Changes in the molecular mobility of freeze-dried formulations that occurred at temperatures below the glass transition temperature could be detected as the molecular mobility-changing temperature (Tmc), at which dextran protons started to exhibit a Lorentzian relaxation decay due to higher mobility in addition to a Gaussian relaxation decay. Tmc increased as the molecular weight of dextran increased. The proportion of dextran protons which exhibited the higher mobility relaxation process (Phm) at temperatures above Tmc decreased as the molecular weight of dextran increased. Protein stability was closely related to molecular mobility. The temperature dependence of the denaturation rate changed at around Tmc, and denaturation in the microscopically liquidized state decreased as Phm decreased with increasing molecular weight of dextran. CONCLUSIONS: The effect of the molecular weight of dextran on the protein stability of freeze-dried BGG formulations could be explained in terms of the parameters obtained by 1H-NMR such as Tmc and Phm. These parameters appear to be useful in preformulation and stability prediction of freeze-dried formulations.

Calorimetry, Differential Scanning↗
PubMed1997

Stereoselective 4'-hydroxylation of phenytoin: relationship to (S)-mephenytoin polymorphism in Japanese.

AIMS: The aim of this study was to clarify whether phenytoin (PHT) stereoselective hydroxylation cosegregates with (S)-mephenytoin phenotype. METHODS: A single dose of PHT (100 mg) was administered orally to six healthy Japanese subjects in whom the genotype and phenotype of CYP2C19 had been determined previously. The urinary excretion profiles of the metabolites of PHT, (R)- and (S)-p-HPPH [5-(4-hydroxyphenyl)-5-phenylhydantoin] up to 361 postdose were compared between the two groups of poor metabolizers (PMs, n = 3) and extensive metabolizers (EMs, n = 3) with respect to CYP2C19. CYP2C9 genotype was also determined. RESULTS: All the alleles were found to be wild type (Arg144 Tyr358Ile359Gly417) in each subject. The mean value for cumulative urinary excretion of unchanged PHT was not significantly different between the PMs and the EMs. However, recovery of (R)-p-HPPH at 36 h was 3.5-fold lower and that of (S)-p-HPPH 1.3-fold lower in PMs than in EMs. Although the mean urinary excretion values for both metabolites were significantly lower in the PMs than in the EMs, the difference between the two groups was larger for (R)-p-HPPH. A significant negative correlation was observed between the hydroxylation index of omeprazole (the ratio between the serum concentrations of omeprazole and hydroxyomeprazole in blood samples drawn 3 h after drug intake) and the log10 0-12 h urinary recovery of (R)-p-HPPH. CONCLUSIONS: In humans, the 4'-hydroxylation of PHT is highly stereoselective towards formation of the (S)-enantiomer. Thus, (S)-hydroxylation by CYP2C9 might be the major determinant of the disposition of PHT. However, these results support the hypothesis that the stereoselective hydroxylation pathway of PHT to form (R)-p-HPPH cosegregates with the CYP2C19 metabolic polymorphism.

Administration, Oral↗
PubMed1997

Circulating soluble selectins in Kawasaki disease.

To investigate the significance of circulating adhesion molecules associated with leucocyte-endothelial cell interaction in Kawasaki disease (KD), serum levels of soluble E-, P-, L-selectin (sE-, sP-, sL-selectin), and vascular cell adhesion molecule-1 (VCAM-1) were measured in 16 patients with KD, eight with other febrile diseases, six with Henoch-Schonlein purpura (HSP), and 10 healthy children using an ELISA. Serum sE-selectin levels from patients in the acute phase of KD were significantly higher than from those in other groups (P < 0.01). The levels of sP-selectin in the subacute phase of KD were significantly higher than in other groups (P < 0.01). Serum sL-selectin levels tended to rise in the convalescent phase of KD. There were also significant correlations between sE-selectin levels and C-reactive protein (r = 0.80, P < 0.0001), and between sP-selectin levels and platelet counts (r = 0.57, P < 0.0001) in KD patients. These data indicate that circulating soluble forms of three selectins may have different kinetics during the clinical course of KD, suggesting that they may reflect its inflammatory process.

Child↗
PubMed1997

Analysis of the distribution of Na+/H+ exchanger isoforms among the plasma membrane subfractions of bovine kidney cortex: reevaluation of methods for fractionating the brush-border and the basolateral membranes.

Distribution of the NHE1 and the NHE3 isoforms of Na+/H+ exchanger in the plasma membranes of bovine kidney cortex was analyzed. Fractionation of the plasma membranes by centrifugation on a Percoll density gradient resulted in clear separation of the basolateral membranes (BLM) from the brush-border membranes (BBM), with Na+,K+-ATPase and aminopeptidase M as their respective marker enzymes. Under these conditions, a 110 kDa protein cross-reactive with an anti-NHE1 antibody was detected exclusively in the BLM fractions, while a 90 kDa protein cross-reactive with an anti-NHE3 antibody was detected in the BBM fractions. A conventional Mg2+-precipitation method for obtaining the BBM, which is adequate with rabbit kidney as a starting material, turned out to be inadequate with bovine kidney cortex, since a considerable amount of the 110-kDa NHE1 protein was detected in the bovine kidney BBM fraction prepared by this procedure, together with the 90-kDa NHE3 protein. Percoll density gradient centrifugation is thus strongly recommended for the fractionation of BBM and BLM of bovine kidney cortex. The bovine NHE1 isoform was shown to be unique in that it is far less sensitive to the inhibition by ethylisopropylamiloride than that of other species.

Amiloride↗
PubMed1997

Expression of the human UDP-galactose transporter in the Golgi membranes of murine Had-1 cells that lack the endogenous transporter.

In our previous study, we demonstrated that UDP-galactose transporter cDNAs (hUGT1 and hUGT2) were able to complement the genetic defect of murine Had-1 cells that were deficient in the UDP-galactose transporter, and that the microsomal vesicles isolated from Had-1-transformants, which were obtained through transfection with these cDNAs, had recovered the ability to uptake UDP-galactose [Ishida, N. et al. (1996) J. Biochem. 120, 1074-1078]. In this report, we describe the preparation of peptide antibodies that recognize the hUGT isozymes, and the detection of hUGT proteins expressed in the transformants. The occurrence of the endogenous hUGT1 protein in HeLa cells was also detected. Using the hUGT1-specific antibodies, the subcellular localization of hUGT1 in the Golgi membrane was demonstrated by immunofluorescence microscopy and subcellular fractionation. These studies led us to develop a simple procedure, based on Percoll density gradient centrifugation, for preparing functional Golgi vesicles from the hUGT1-transformed Had-1 cells, that will facilitate future biochemical analyses of the UDP-galactose transporter for the elucidation of its structure-function relationship.

Amino Acid Sequence↗
PubMed1997

Extensive facial strawberry mark associated with cerebellar hypoplasia and vascular abnormalities.

Strawberry mark is considered a benign hemangioma with a tendency toward spontaneous regression and a benign prognosis. Recently, some papers have reported complications of large facial strawberry marks. We report a infant girl with an extensive strawberry mark on the left side of the face associated with ipsilateral cerebellar hypoplasia and Dandy-Walker malformation. Abnormal branching of the aortic arch was also found.

Aorta, Thoracic↗
PubMed1997

Transient erythrophagocytosis in Diamond-Blackfan anemia.

We report on a 4-month-old Japanese infant girl with Diamond-Blackfan anemia (DBA) as shown by congenital macrocytic pure red cell hypoplasia with marked reduction of erythroid precursors in bone marrow, reticulocytopenia, increased fetal hemoglobin, and elevated adenosine deaminase activity in peripheral blood. She responded poorly to conventional doses of corticosteroids, however, with high-dose corticosteroids she responded with reticulocytosis and an elevation of hemoglobin level above 12 g/dL. Erythrophagocytosis was noted during the tapering period of prednisone when her hemoglobin level declined to 7.6 g/dL and reticulocyte level to 0.4%. At that time, the erythrophagocytosis was noted in about 60% of marrow histiocytes. These findings were not observed prior to or during the high dose prednisone therapy. We speculate that one of the causes of pure red cell aplasia and reticulocytopenia in DBA is mediated by erythrophagocytosis.

Bone Marrow↗
PubMed1997

NG-methyl-L-arginine, an inhibitor of nitric oxide synthase, affects the central nervous system to produce peripheral hyperglycemia in conscious rats.

To determine whether the nitric oxide (NO) system in the central nervous system (CNS) is involved in the peripheral metabolism of carbohydrate we injected NG-methyl-L-arginine (L-NMA), an inhibitor of NO synthase, into the third cerebral ventricle of unanesthetized, unrestrained rats and determined the plasma level of glucose. This intracerebroventricular (i.c.v.) injection of the drug increased the plasma level of glucose dose-dependently, whereas an intravenous (i.v.) injection had no effect. The hyperglycemia thus induced was suppressed by concomitant i.c.v. or prior i.v. administration of L-arginine. Concomitant administration of D-arginine did not affect hyperglycemia by L-NMA. The i.c.v. injection of 5 x 10(-6) mol L-NMA increased plasma levels of glucose, epinephrine and norepinephrine, and serum levels of glucagon. However, plasma levels of insulin were unchanged, despite the presence of hyperglycemia. The hyperglycemia produced by L-NMA was completely inhibited by bilateral adrenalectomy. It was also inhibited by prior intraperitoneal injection of phentolamine, but not of propranolol or naloxone. Results suggest that L-NMA acts on the CNS to stimulate adrenal secretion of epinephrine and, subsequently, to elevate glucose levels in the peripheral blood. The NO system thus seems to be involved in the neural regulation of the adrenal by the GNS, which in turn regulates peripheral blood glucose levels.

Adrenalectomy↗