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Biomedical subjects

S Yoshioka

Publications and source records attributed to S Yoshioka.

At least 217 records · Page 12Linked to original sources

Protein denaturation in dosage forms measured by differential scanning calorimetry.

The stability of beta-galactosidase dosage forms was studied by differential scanning calorimetry (DSC). It was found that the observed enthalpy of thermal denaturation was approximately in proportion to remaining enzyme activity, and denaturation temperature was related to protein stability. These results suggest that DSC can be used to determine native proteins in dosage forms and to clarify the factors affecting protein stability. The DSC method seems to be more convenient than conventional activity assay methods, and useful to follow protein denaturation during the manufacturing process and storage of dosage forms.

Calorimetry, Differential Scanning↗

[Ruptured cerebral aneurysm associated with coarctation of the aorta].

We present a 33-year-old female who had a ruptured aneurysm at the trifurcation of the right middle cerebral artery accompanied by coarctation of the aorta. The aneurysm was successfully clipped 15 hours after the attack of subarachnoid hemorrhage and approximately 3 months later the coarctation was surgically treated. Many authors reported that the incidence of cerebral aneurysm was higher in the patients with coarctation than the general population. Our review of the literatures, however, revealed that the incidence of cerebral aneurysm was the same in the population with or without coarctation. The incidence of rupture was higher when the aneurysms was accompanied by coarctation. The average age of the patients at the aneurysmal rupture was younger in the patients with coarctation than the patients without coarctation. These findings suggested that the growth and rupture of aneurysm in the patient with coarctation are related to the hypertension and atherosclerosis. Treatment of the patients with intracranial ruptured aneurysm accompanied by coarctation should begin with the clipping of the aneurysm, and then the coarctation surgically repaired. If the aneurysm is unruptured coarctation should be repaired first, and then the aneurysm clipped.

Adult↗

[Investigation of low-contrast signal detection in computed radiography (CR)].

Threshold contrasts of low-contrast objects were compared between screen-film and computed radiography (CR) systems. Effects of incident exposure to the imaging plate (IP) and contrast enhancement on the detectability of low-contrast objects were also studied. We employed 18-alternative forced-choice (18AFC) experiments to study the dependence of the threshold contrasts of the test objects on the incident exposure, object size, and contrast enhancement. The results indicated that the threshold contrasts of CR system were comparable to that of the medium-speed screen-film system and increased by decreasing x-ray exposures. Although threshold contrasts decreased by contrast enhancement, the magnitude of improvement depended on the object size and incident exposure.

Radiographic Image Enhancement↗

[Constructions of compensating screen of chest radiography and its clinical applications--evaluation of normal anatomical structures].

We have constructed compensating screens which have different sensitivities for the pulmonary hilum and mediastinum in contrast to the lung. With these screens the regions of the mediastinal and retrocardiac areas are simultaneously displayed with optimal contrast on postero-anterior (PA) chest radiographs. The potential clinical use of compensating screens was evaluated in 67 patients for visibility of the anatomical structures in comparison with conventional screens. Confidence test was used to compare the detectability of the various anatomical structures of the chest. The chest radiographs obtained with compensating screens improved visibility of the anatomical structures including the tracheal bifurcation, right and left main bronchus, and paraesophageal line.

Evaluation Studies as Topic↗

High-dose immunoglobulin for juvenile myasthenia gravis.

A four-year-old girl with the ocular type of myasthenia gravis was effectively treated with intravenous high dose human immunoglobulin. Since conventional anti-choline-esterase drugs failed to induce a satisfactory outcome and the patient continued to suffer from amblyopia, high-dose immunoglobulin was tried according to the method of Gados. Subsequently, she became asymptomatic and her anti-acetylcholine-receptor antibody titer decreased gradually to normal. Currently, she is six years old and continues to be free from complaints and on no medication.

Blepharoptosis↗

Epimerization and racemization of some chiral drugs in the presence of cyclodextrin and liposomes.

The effects of alpha-, beta-, gamma- and dimethyl-beta-cyclodextrins (alpha-, beta-, gamma- and DM-beta-CyDs) and liposomes on epimerization or racemization of etoposide, ethiazide and carbenicillin were examined kinetically. alpha- and beta-CyDs accelerated both epimerization and hydrolysis of carbenicillin. They had no effect on epimerization of etoposide, and did not affect racemization and hydrolysis of ethiazide. DM-beta-CyD retarded epimerization of etoposide, hydrolysis of picroetoposide (which is an epimer of etoposide), and racemization and hydrolysis of ethiazide, but had no effect on epimerization and hydrolysis of carbenicillin. gamma-CyD retarded epimerization of etoposide and hydrolysis of picroetoposide. On the other hand, gamma-CyD accelerated epimerization of carbenicillin. It is suggested that the formation of inclusion complexes between CyDs and etoposide, picroetoposide and ethiazide inhibited the attack of bases such as OH- and buffer components, thereby retarding epimerization, racemization and hydrolysis. On the other hand, alpha-, beta- and gamma-CyDs increased the reactivity of carbenicillin through the OH group, accelerating its epimerization and hydrolysis. Liposomes retarded epimerization of etoposide, hydrolysis of picroetoposide and racemization of ethiazide. Liposomes did not affect epimerization and hydrolysis of carbenicillin. These differences in the effect of liposomes on reactivity may be interpreted in terms of the solubility of the drugs.

Chemical Phenomena↗

A modified signal intensity equation of Carr-Purcell-Meiboom-Gill pulse sequence for MR imaging.

The signal intensity equation of Carr-Purcell-Meiboom-Gill (CPMG) pulse sequences for magnetic resonance imaging was modified to: S(n) = k.M0.exp (-n.Te/T2) [1-exp (-Tr/T1)] where S(n) is a signal intensity of "n-th" echo; k, constant; M0, initial longitudinal magnetization; n, echo number; Te, echo interval; and Tr, recovery time [Tr = TR-(N-1/2).Te; TR, repetition time; N, number of echoes]. To evaluate the accuracies of T1 and T2 values calculated from this modified equation, a phantom experiment using five tubes filled with 0.5 to 8 mM copper sulfate solutions was performed using a 0.14-T resistive whole-body MR scanner and a spectrometer system. The differences between the image values by this equation and the bulk values by the spectrometer were less than 6.2% (mean +/- S.D., 3.3 +/- 2.1%) in T2 and 15.6% (10.4 +/- 4.9%) in T1 (except 8 mM). By this modification, not only the image T2 value with a high accuracy but the image T1 value can be obtained simultaneously.

Magnetic Resonance Imaging↗

[Uptake and localization of neocarzinostatin in malignant glioma. Experimental study by immunofluorescent staining method].

The authors studied the localization of neocarzinostatin (NCS) in cultured cells and in tumor-bearing rats by means of immunofluorescent staining. Anti-NCS antibody was obtained through immunization of rabbits with NCS. Cellular uptake of NCS was dose-dependent (1.0 to 1000 micrograms/ml) in 9L rat gliosarcoma cells in monolayer. In monolayer cells of 9L, KMG-4 (derived from human glioblastoma), and KMS II (human ependymoma) treated with 1 mg/ml of NCS, drug uptake occurred within a few seconds. Accumulation was much higher in the cytoplasm than in the nucleus and, although nuclear uptake increased slightly over time, there appeared to be no increase in total cellular uptake. Mitotic cells, which were spherical in culture, showed greater intracellular accumulation than other cells. There was no significant difference in uptake among non-mitotic cells. Cells surviving 20 hours of treatment retained accumulation as high as that in killed cells. In KMG-4 monolayers, cytoplasmic and nuclear NCS distribution still differed, whereas 9L monolayers exhibited more even intracellular distribution. In 9L spheroid models treated with 1 mg/ml of NCS, the drug permeated almost all layers within 10 minutes, and at 120 minutes had heavily accumulated in the central necrotic areas. In rats with transplanted brain tumors, NCS selectively accumulated in neoplastic tissues following intra-arterial administration. However, NCS uptake by arterial endothelium was also seen, which suggests the potential for vascular toxicity. The therapeutic value of NCS is discussed in terms of its pharmacokinetic characteristics.

Animals↗

Polyol content of cerebrospinal fluid in brain-tumor patients.

In order to investigate whether cerebrospinal fluid (CSF) polyols are consumed by brain tissue, the concentration of seven polyols in the CSF and the serum of 30 patients with intracranial tumor and 17 control individuals was measured by gas chromatography. The mean polyol content in the control samples showed that the fructose, inositol, and glucitol levels were significantly greater in CSF than in serum. A comparison of the lumbar CSF from control subjects and 11 patients with malignant tumors exposed to the CSF showed the fructose and inositol levels to be significantly lower (54% and 45%, respectively) and the glucose content to be slightly higher (110%) in the tumor cases. These differences were markedly greater in the ventricular than in the lumbar CSF and greater in patients with tumors exposed to the CSF space than in those with tumors buried in the brain tissue. In ventricular CSF obtained from seven patients with malignant brain tumors before and after radio- and/or chemotherapy, significant increases in fructose (34%) and glucitol (48%) levels were found, but the other polyols did not change significantly. In culture, the human glioblastoma cell growth rate was higher in the medium containing fructose and glucose than in that containing glucose alone. A notable amount of fructose and glucose was consumed by cultured glioblastoma cells. The roles of polyols contained in CSF and the effects of fructose on the growth of cultured glioblastoma cells are discussed in light of these findings and of previous reports.

Adult↗

Relationship between histologic type of primary lung cancer and carbon-11-L-methionine uptake with positron emission tomography.

L-[Methyl-11C]-methionine [( 11C]methionine) has proved to be one of the useful amino acids for the diagnosis of human cancer. We examined whether there was any correlation between [11C]methionine uptake and histologic type of primary lung cancer. Sixteen patients with nine squamous cell carcinoma, five large cell carcinoma, one small cell carcinoma, and one adenocarcinoma were studied using positron emission tomography (PET). All patients had high accumulation of [11C]methionine in lung tumors. We evaluated [11C]methionine uptake into the tumor by a semiquantitative value, DUR (Differential Uptake Ratio). There was significant difference (p less than 0.01, Mann-Whitney test) of [11C]methionine uptake between large cell carcinoma (3.98 +/- 0.27) and squamous cell carcinoma (2.92 +/- 0.30). The result suggested that there was correlation between [11C]methionine accumulation and the histologic type of lung cancer. This indicates a new potential applicability of [11C]methionine PET for the study of lung cancer.

Adenocarcinoma↗

[Dissolution of silver-based alloys under dynamic conditions and its relation to cytotoxicity (in vitro)].

Dissolution of eight silver-based alloys for small casting was investigated under dynamic conditions that accelerated abrasive particle wear. The extract was separated into filtrate and sediment with a 0.22 micron cellulose acetate filter and added to cell culture to study cytotoxicity. Dissolution of silver exhibited the highest dissolution into the extract in the alloys tested. Tin was eluted from six alloys, and indium from five alloys. Following filtration with a 0.22 micron filter, silver, tin and indium were not detected in the filtrate. Zinc was also eluted from all of the alloys, ranging from 5.073 ppm to 29.52 ppm. The amount of zinc in the filtrate was one fifth to tenth of that of the extract. Copper was eluted from two alloys. The amounts of copper in the filtrate and extract were similar. The extract was most cytotoxic, while the filtrate was also cytotoxic except for after one day extraction. The present results demonstrate that extraction under dynamic conditions appears to be useful for investigation of metal corrosion and cytotoxicity in vitro.

Cells, Cultured↗

[Clinical significance of sialic acid in the CSF; in relation to the malignancy and leptomeningeal dissemination].

We examined the level of sialic acid in cerebrospinal fluid (CSF) in 20 patients with brain tumor, and 5 patients with non-neoplastic disease of central nervous system. CSF concentration of sialic acid in the patients with malignant and semi-malignant or benign brain tumor was 5.26 +/- 2.39 mg/dl, and 1.82 +/- 1.61 mg/dl, respectively. In patients with non-neoplastic disease, it was 1.64 +/- 1.53 mg/dl. The difference between groups was statistically significant (p less than 0.005). In two patients with malignant brain tumor, the level of sialic acid was decreased by radiation therapy or intrathecal chemotherapy. In conclusion, CSF concentration of sialic acid was significant of diagnosis of brain tumor character of malignancy, and effect of therapy for CSF dissemination.

Arachnoid↗

Covalent binding of 4-nitrobenzyl mercaptan S-sulfate to the sulfhydryl groups of hepatic cytosolic proteins and bovine serum albumin with mixed disulfide bond formation.

4-Nitrobenzyl [35S]mercaptan S-sulfonic acid ([35S]NBM S-sulfate), a new type of reactive metabolite of the thiol [35S]NBM in rat liver cytosol fortified with 3'-phosphoadenosine 5'-phosphosulfate, bound rapidly and covalently at pH 7.4 and 37 degrees C to the sulfhydryl groups of rat liver cytosolic proteins with formation of disulfide bonds. From the radioactive proteins was isolated and identified the sole amino acid adduct, S-([35S]NBM)cysteine, after their acid hydrolysis under the anaerobic conditions. Bovine serum albumin (BSA), a model protein with a single SH group, also reacted readily with radioactive NBM S-sulfate to form a disulfide bond in stoichiometric manner. S-([35S]NBM)-cysteine was also isolated and identified as the sole amino acid adduct from the well-washed, radioactive BSA after the same anaerobic acid hydrolysis. A normal hepatic level of GSH not only retarded the BSA-NBM adduct formation completely, but also detached the radioactivity from BSA by the reduction of the disulfide bond with formation of [35S]NBM and its disulfide. Of twenty-one amino acids examined at pH 7.4 and 37 degrees C, only cysteine reacted with NBM S-sulfate and afforded S-(NBM)cysteine with concomitant formations of S-sulfocysteine, cystine, NBM, and its disulfide.

Animals↗

Characterization of new oral antidiabetic agent CS-045. Studies in KK and ob/ob mice and Zucker fatty rats.

CS-045 is a new oral antidiabetic agent that was effective in insulin-resistant diabetic animal models, including the KK mouse, the ob/ob mouse, and the Zucker fatty rat. CS-045 was not effective in the streptozocin-treated mouse, an insulin-deficient diabetic animal model. In fed KK mice, CS-045 lowered the plasma glucose levels in a dose-dependent manner after a single oral administration, and the hypoglycemic effect lasted for at least 18 h. In normal rats, however, plasma glucose levels were not changed after administration of CS-045. CS-045 when given chronically (2 wk) to diabetic KK and ob/ob mice as a 0.2% food admixture dramatically improved hyperglycemia, hyperinsulinemia, and hypertriglyceridemia to near-normal values and decreased plasma lactate, free fatty acid, and ketone body levels without reducing food intake or body weight. In the obese Zucker fatty rat, oral administration of CS-045 had a similar effect in lowering plasma glucose, insulin, triglyceride, free fatty acid, lactate, and ketone body levels. The CS-045-treated Zucker fatty rats showed increased glucose tolerance and decreased insulin secretion in response to oral glucose. After 9 days of treatment, insulin binding to adipocyte plasma membranes from both CS-045-treated Zucker fatty rats and KK mice was increased. Furthermore, 2-deoxyglucose uptake in CS-045-treated adipocytes was increased and the insulin dose-response curve was shifted to the left. These findings suggest that CS-045 increases not only insulin sensitivity but also insulin responsiveness. Based on its pharmacological profile, CS-045 is a new orally effective antidiabetic agent that may reduce abnormalities of glucose and lipid metabolism in obese and non-insulin-dependent diabetes mellitus patients with insulin resistance.

Adipose Tissue↗