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Biomedical subjects

S Yoshioka

Publications and source records attributed to S Yoshioka.

At least 163 records · Page 9Linked to original sources
PubMed1994

Physical stability and protein stability of freeze-dried cakes during storage at elevated temperatures.

The relationship between physical stability of freeze-dried cakes and protein stability during storage was studied using beta-galactosidase as a model protein and inositol as an excipient. Amorphous samples freeze-dried from solutions containing the enzyme and various concentrations of inositol in sodium phosphate buffer (50 mM, pH 7.4) were stored for 7 days over P2O5 at 40 to 70 degrees C. Structural collapse and inositol crystallization were observed in some of the samples, depending on the formulation and storage temperature. The physical stability of freeze-dried samples was also studied by differential scanning calorimeter (DSC). Inositol showed a protein-stabilizing effect when its amorphous form was retained during storage, regardless of structural collapse. However, crystallization of inositol during storage removed its stabilizing effect. Addition of water-soluble polymers such as dextran, Ficoll and carboxymethyl cellulose sodium salt (CMC-Na) preserved activity of the enzyme by preventing inositol crystallization.

Aspergillus oryzae↗
PubMed1994

Is stability prediction possible for protein drugs? Denaturation kinetics of beta-galactosidase in solution.

Denaturation and aggregation kinetics of Aspergillus oryzae beta-galactosidase in solution were studied in order to determine whether the stability of protein drugs can be predicted. Denaturation of beta-galactosidase, monitored by measuring enzyme activity, conformed to first-order kinetics, whereas aggregation of the denatured form, monitored by high performance size exclusion chromatography, showed a reaction order higher than 1. Denaturation of beta-galactosidase was irreversible and exhibited a biphasic kinetic pattern which could be explained by assuming that two isoenzymes denatured irreversibly at different rates. Linear Arrhenius plots were obtained for the estimated rate constants, and delta H not equal to and delta S++ to were estimated according to the Eyring equation. The estimated delta H++ was much larger than delta H++ observed in usual chemical reactions. The present study suggests that the denaturation of protein drugs can be analyzed by the Eyring equation in the same manner as chemical degradation, contradicting the general consensus that accelerated testing can not be used to predict the stability of protein formulations.

Enzyme Stability↗
PubMed1994

A bayesian approach to Arrhenius prediction of shelf-life.

The use of a bayesian method for estimating the shelf-life of pharmaceutical formulations is evaluated and compared with classical linear regression. Using three real data sets, the greater flexibility provided by the bayesian approach is demonstrated. In particular, the bayesian approach enabled the consideration of cases when the error distribution is non-normal. However much more computation is required with the bayesian method.

Bayes Theorem↗
PubMed1994

Bone marrow transplantation for erythroleukemia: a case report.

A 2 year old girl was diagnosed as having erythroleukemia (EL; M6 according to the French-American-British classification). After one course of low-dose cytosine arabinoside (Ara-C), complete remission was obtained. After three courses of low-dose Ara-C for consolidation, allogeneic bone marrow transplantation was performed from HLA-identical sibling. The course of post-transplantation was uneventful. Two years after transplantation, she continues to have durable engraftment and remission. In children with EL, conventional chemotherapy appears to be inadequate for producing durable long-term disease-free survival. Bone marrow transplantation should be considered in children with EL, in cases where suitable donors are available.

Bone Marrow Transplantation↗
PubMed1994

The aggregation of bovine serum albumin in solution and in the solid state.

The aggregation of bovine serum albumin (BSA) in the solid state and in solution was studied to elucidate the effect of water mobility on the aggregation rate and mechanism. The results suggest that the freeze-dried BSA forms covalently-bonded aggregates via disulphide bonding during storage in the moistened solid state and in solution. The aggregation rate largely depended on the water content. The freeze-dried BSA to which a small amount of water was added (in the moistened state) was found to be more liable to aggregation than that in solution. The aggregation rate in in the moistened solid state exhibited a maximum at a very low level of moisture. In contrast, the aggregation rate in solution increased with increasing ratio of water to protein (with decreasing protein concentration). The results suggest that the increased rate is related to the increase in water mobility, as measured by the spin-lattice relaxation time, T1, of water using 17O NMR, with increasing ratio of water to protein.

Chromatography, Gel↗
PubMed1994

Increased expression of human 63-kD heat shock protein gene in Kawasaki disease determined by quantitative reverse transcription-polymerase chain reaction.

To investigate the possible role of heat shock protein (HSP) in the pathogenesis of Kawasaki disease (KD), we determined the expression of 63-kD HSP (P1 protein) gene in the leukocytes from the peripheral blood of 20 patients with KD, 20 patients with various other febrile diseases, and 10 healthy children using the quantitative reverse transcription-polymerase chain reaction technique. Although a low but constitutive expression of HSP was observed in the control patients and healthy children, the expression of HSP63 mRNA was significantly higher during the acute phase of KD. Because mycobacterial HSP65, a cognate of human HSP63, is a common immunogen in bacterial species, and because the major immunopathologic feature of KD is reportedly an abnormally activated immune system, it suggests that an increased level of HSP63 gene transcription may be associated with the pathogenesis of KD.

Base Sequence↗
PubMed1994

Troglitazone prevents the inhibitory effects of inflammatory cytokines on insulin-induced adipocyte differentiation in 3T3-L1 cells.

Tumor necrosis factor (TNF) is implicated in wasting syndromes and insulin resistance in chronic infection and obese-linked diabetes. TNF (10 ng/ml) inhibited adipocyte differentiation of 3T3-L1 cells, and in these TNF treated cells little insulin-stimulated glucose uptake was observed. Treatment of 3T3-L1 cells with troglitazone (1-10 microM) partially prevented this inhibitory effect of TNF on adipogenesis, and enhanced expression of C/EBP alpha and GLUT4, even in the presence of TNF. Troglitazone also prevented the inhibitory effects of interleukin-1, interleukin-6, and leukemia inhibitory factor, but not of transforming growth factor beta on adipocyte differentiation of 3T3-L1 cells. These effects might contribute to the antidiabetic effect of troglitazone in obese diabetic animals.

3T3 Cells↗
PubMed1994

Preferential uptake of lactosylceramide-bearing dipalmitoylphosphatidylcholine-liposomes into liver: role of membrane fluidity.

The effect of the membrane fluidity of lactosylceramide (LacCer)-bearing liposomes on their liver uptake was investigated in rats. Liposomes consisting of phosphatidylcholine (PC): cholesterol:dicetylphosphate:LacCer (7:2:1:1, molar ratio) were prepared with various fluidities using dipalmitoylphosphatidylcholine (DPPC), dimyristoylphosphatidylcholine (DMPC) and egg PC. These liposomes were all equally stable in serum and were small enough to pass freely through the fenestrae and be taken up easily by liver cells. The LacCer modification of DPPC-liposomes markedly facilitated blood clearance, whereas no enhancing effect of LacCer was observed with egg PC- and DMPC-liposomes. Tissue distribution studies showed the preferential liver uptake of LacCer-bearing DPPC-liposomes, which was largely compatible with the rapid clearance induced by the LacCer modification. In addition, electron spin resonance (ESR) spectroscopic analysis revealed that the LacCer modification of DPPC-liposomes significantly enhanced the order parameter S, indicating that LacCer-bearing DPPC-liposomes were the most rigid of those used in this study. These observations suggest that the membrane fluidity of liposomes in vivo is a crucial factor for their preferential liver uptake.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1994

Effect of mannitol crystallinity on the stabilization of enzymes during freeze-drying.

The stabilizing effect of mannitol during the freeze-drying of proteins was studied using L-lactate dehydrogenase (LDH, rabbit muscle), beta-galactosidase (Escherichia coli) and L-asparaginase (Erwinia chrysanthemi) as model proteins. Crystallization of mannitol was studied by powder X-ray diffraction and differential scanning calorimetry (DSC), in relation to the stabilizing effect. All the enzymes were protected concentration-dependently by amorphous mannitol, but the stabilizing effect was decreased with an increase in mannitol crystallinity. The heat-treatment of frozen solutions above crystallization temperature prior to drying enhanced mannitol crystallization and LDH inactivation. The importance of maintaining excipients in an amorphous state during freeze-drying, previously reported for Aspergillus oryzae beta-galactosidase (K. Izutsu et al., Pharm. Res., 10, 1233 (1993)), was confirmed using three different enzymes.

Animals↗
PubMed1994

[A case of hepatocellular carcinoma with lumbar bone metastasis with high uptake of 18F-fluorodeoxygalactose in PET].

18F-fluorodeoxygalactose (18FDGal) is a tracer for the evaluation of galactose metabolism in the tissue. PET with 18FDGal was performed in a hepatoma (HCC) patient with lumbar bone metastasis. The image at 45 min after i.v. injection of 18FDGal demonstrated very high uptake by the bone metastasis with tumor-to-surrounding normal tissue ratio of 36. The tumor uptake expressed by differential absorption ratio was much higher than that in the cirrhotic liver and kidney. The result indicated that the HCC maintained high activity of galactose metabolism and rises the potential of this tracer for detecting extrahepatic metastases of HCC using PET.

Carcinoma, Hepatocellular↗
PubMed1994

[A simple method for measurement of cerebral blood flow using 123I-IMP SPECT with calibrated standard input function by one point blood sampling; validation of calibration by one point venous blood sampling as a substitute for arterial blood sampling].

In a simplified method for measurement of cerebral blood flow using one 123I-IMP SPECT scan and one point arterial blood sampling (Autoradiography method), input function is obtained by calibrating a standard input function by one point arterial blood sampling. A purpose of this study is validation of calibration by one point venous blood sampling as a substitute for one point arterial blood sampling. After intravenous infusion of 123I-IMP, frequent arterial and venous blood sampling were simultaneously performed on 12 patients of CNS disease without any heart and lung disease and 5 normal volunteers. The radioactivity ratio of venous whole blood which obtained from cutaneous cubital vein to arterial whole blood were 0.76 +/- 0.08, 0.80 +/- 0.05, 0.81 +/- 0.06, 0.83 +/- 0.11 at 10, 20, 30, 50 min after 123I-IMP infusion, respectively. The venous blood radioactivities were always 20% lower than those of arterial blood radioactivity during 50 min. However, the ratio which obtained from cutaneous dorsal hand vein to artery were 0.93 +/- 0.02, 0.94 +/- 0.05, 0.98 +/- 0.04, 0.98 +/- 0.03, at 10, 20, 30, 50 min after 123I-IMP infusion, respectively. The venous blood radioactivity was consistent with artery. These indicate that arterio-venous difference of radioactivity in a peripheral cutaneous vein like a dorsal hand vein is minimal due to arteriovenous shunt in palm. Therefore, a substitution by blood sampling from cutaneous dorsal hand vein for artery will be possible. Optimized time for venous blood sampling evaluated by error analysis was 20 min after 123I-IMP infusion, which is 10 min later than that of arterial blood sampling.

Amphetamines↗
PubMed1994

[Two cases of malignant effusion treated successfully by loco-regional administration of carboplatin].

We encountered two cases of malignant effusion treated successfully by loco-regional administration of carboplatin (CBDCA). One case was a 60-year-old male showing recurrent non-small cell lung cancer (adenocarcinoma) with pericarditis carcinomatosa. A drainage from the pericardial cavity was performed and a total dose of 600 mg (single dose, 300 mg) of CBDCA was administered into the cavity. Malignant effusion disappeared and radiographic improvement was also observed. No pericardial effusion was observed for about 4 months after the loco-regional treatment, till he died of lung cancer. Another case was a 58-year-old male having invasive thymoma (mixed cell type) with pleuritis carcinomatosa. He received palliative radiation therapy and systemic cancer chemotherapy concurrently. As a loco-regional therapy, drainage from the pleural cavity was performed, and 300 mg of CBDCA and 10 KE of OK-432 were administered into the cavity. A remarkable reduction of pleural effusion was observed after the therapy. No increase of pleural effusion has been observed radiographically for about 18 months, and the patient is still alive with the tumor. The side effects due to loco-regional administration of CBDCA were quite tolerable in both cases.

Adenocarcinoma↗
PubMed1994

[Neurocutaneous melanosis--a case report].

Neurocutaneous melanosis is a rare congenital phacomatosis characterized by the presence of large or multiple congenital melanocytic nevi and benign or malignant pigmented cell tumors of the leptomeninges. A 14-month-old boy was admitted with a recent history of vomiting and drowsiness. He was found to have multiple congenital melanocytic nevi. Gd-enhanced MRI showed ventriculomegaly and leptomeningeal enhancement in the ambient cistern. CSF cytology revealed abnormal cells with pigmented granules. A diagnosis of hydrocephalus with malignant neurocutaneous melanosis was made. The patient was treated with combination chemotherapy (DAV therapy, ACNU intrathecal perfusion therapy, interferon beta therapy) while controlling intracranial pressure by CSF drainage, but in spite of treatment he died due to rapid progression of leptomeningeal infiltration. Postmortem examination revealed meningeal malignant melanomas predominantly at the base of the brain and benign meningeal melanosis over the cerebral cortex. Newborn infants or infants with large or multiple congenital melanocytic nevi should be carefully followed, especially for the first two years. When hydrocephalus or convulsions occur in patients with skin lesions, Cd-enhanced-MRI and careful CSF cytology studies should be performed to detect meningeal abnormalities.

Humans↗
PubMed1994

[A pharmacokinetic study on high-dose methotrexate administration--the effects of volume changes of parenteral solutions on the elimination rate].

Methotrexate (MTX) serum concentrations were measured in 7 cases (2 patients) in which a high-dose administration of MTX with citrovorum factor rescue for osteogenic sarcoma were performed for repressing activity in the original lesion and satellite micrometastasis. In the pharmacokinetic analysis, the changes of MTX serum concentrations were explained by a 2-compartment open model under the assumption that the elimination rate was proportional to both of volume of parenteral solution and the amount of water intake. It was suggested that MTX serum concentration could be controlled by adjusting the volumes of parenteral solutions. MTX amount in the peripheral compartment was found about ten times larger than that in the central compartment after about 40 h of administration. It is considered that an early increase in the volumes of parenteral solutions is effective to keep the safety level of MTX serum concentration, and continuous infusion is important for avoiding the severe side effects caused by delayed elimination of MTX.

Bone Neoplasms↗
PubMed1993

Regional cerebral blood flow changes of cortical motor areas and prefrontal areas in humans related to ipsilateral and contralateral hand movement.

The regional cerebral blood flow (rCBF) was measured with positron emission tomography (PET) in ten normal right-handed volunteers with the purpose of comparing rCBF changes related to movements of the dominant (right) and non-dominant (left) hand. The hand movement task consisted of sequential opposition of the thumb to each finger. The rCBF measured was compared with a rest state. Movements of the dominant hand and the non-dominant hand, increased CBF significantly in the contralateral motor area (MA) and the premotor area (PMA) with small increases in rCBF in the supplementary motor area (SMA). However, movements of the non-dominant hand also elicited significant ipsilateral increases in rCBF in the MA and PMA (6.3% and 5.0%, respectively). Superior part of the prefrontal area (PFA) of the left hemisphere showed significant CBF increases to both left and right hand movement. Our findings indicate that rCBF changes in the motor areas and the PFA of one hemisphere are not related simply to movement of the contralateral hand. Non-dominant hand movement may in addition require activation of ipsilateral motor areas. That is, there appears to be functional asymmetry in the MA and PFA in humans even in this relatively simple and symmetric motor task.

Adult↗
PubMed1993

Antihypertensive effects of CS-045 treatment in obese Zucker rats.

The association of hypertension with obesity has been well recognized, but the etiology remains poorly understood. Obesity is characterized by hyperinsulinemia, which reflects peripheral insulin resistance. Insulin resistance may participate in the development of hypertension with obesity. CS-045 [(I)-5-[4-(5-hydroxy-2,5,7,8-tetramethylchroman-2-yl-methoxy)be nzy l]-2,4- thiazolidiendion] is a new orally effective antidiabetic agent that potentiates insulin action and reduces insulin resistance in obese Zucker rats and other obese diabetic animals. In this study, we examined the antihypertensive effect of CS-045 in obese male and female Zucker rats as a model of hypertension associated with obesity. CS-045 was administered as a food admixture (approximately 16 and approximately 70 mg/kg/d) for 4 weeks (female) and (approximately 15 and approximately 67 mg/kg/d) 8 weeks (male) in obese Zucker rats at 5 to 7 months of age. CS-045 slightly but significantly decreased plasma glucose levels. Plasma insulin levels were significantly decreased in obese male rats, but were not significantly decreased in obese female rats. Drug administration led to significant decreases in plasma triglyceride and cholesterol levels and systolic blood pressure (SBP) in a dose-dependent manner from 1 week after administration in obese Zucker rats. CS-045 increased urinary sodium excretion, sodium/potassium ratio, and creatine clearance in a dose-dependent manner, and also led to a remarkable decrease in urinary protein excretion. However, CS-045 did not reduce urinary catecholamine excretion. These data indicate that CS-045 may promote renal sodium excretion and improve decreased glomerular filtration rates, which may reflect the amelioration of insulin resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗