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Biomedical subjects

S Yoshioka

Publications and source records attributed to S Yoshioka.

At least 199 records · Page 11Linked to original sources
PubMed1991

Inactivation kinetics of enzyme pharmaceuticals in aqueous solution.

The kinetics of enzyme inactivation in aqueous solution of neutral pH were studied for alpha-chymotrypsin, bromelain, and kallikrein. Inactivation of alpha-chymotrypsin and bromelain followed simple first-order kinetics, and the rate constant obtained conformed to the Arrhenius relationship. Kallikrein, however, presented more complicated kinetics of inactivation, which could be described by a kinetic expression combining a reversible and an irreversible pathway. Nonlinear regression analysis suggested that the rate constants conform reasonably well to the Arrhenius relationship. The results suggest that inactivation of enzymes in aqueous solution can be modeled even if the profile is complicated and that the inactivation rates can be predicted based on the relationship between the parameter estimates and temperature.

Bromelains↗
PubMed1991

Changes of anti-HB core antibody in children with positive HB surface antigen.

To elucidate the clinical courses of children chronically infected with HB virus (HBV), RIA values of anti-HBc were surveyed in 88 cases with positive HBs antigen. Among 56 children with positive HBe antigen, 20 had negative, indefinite or low titers of anti-HBc, and 18 (90%) of them had no liver malfunction. Out of 30 cases with abnormal liver function tests, 28 (93%) had high titers of anti-HBc. Follow-up study for a period of over 12 months reveals that serum HBe antigen disappeared in 10 out of the 40 cases who were positive for this antigen. All of the 10 cases had liver malfunction and high levels of anti-HBc. Among 12 children with initially positive anti-HBe, five had high titers of anti-HBc. Out of 13 children who once had high levels of anti-HBc, 3 showed reduction in titers of anti-HBc during the follow-up period in accordance with decrease in activity of hepatitis. Four out of 16 who initially had HBe antigen and low titers of anti-HBc showed high titers of anti-HBc during the observation period, while only one of 33 who had HBeAg and a high titer of anti-HBc went to the low titer group of anti-HBc, though continuously positive for HBe antigen. We presume that high levels of anti-HBc indicate previous or current liver damage due to HBV infection, while low titers of anti-HBc indicate that HBV-derived liver damage has not yet occurred or that a long time has passed since the last episode of liver damage subsided.

Adolescent↗
PubMed1991

Study to establish normal values for portal vein blood flow in children using a duplex ultrasound system.

Portal vein blood flow in healthy children was measured using a duplex ultrasound system consisting of a B mode linear scanner and a single Doppler transducer. Portal blood flow volume (PBFV) correlated with age, height, weight and body surface area. Increases in PBFV with age were greater in boys than girls. A correlation was noted between the diameter of the portal vein and PBFV (r = 0.89). However, the maximum portal blood flow velocity (Vmax) did not correlate with age, height, weight or body surface area. Increases in PBFV in accordance with physical development was thought to depend mainly on widening of the portal vein and not on acceleration of portal blood flow velocity. The formula for calculating PBFV by multivaliate statistical analysis is as follows: PBFV(ml/min) = 30.1 x age(yrs) - 1.07 x height(cm) = 3.31 x weight(kg). Portal vein flowmetry using a duplex ultrasound system may be useful for evaluation of the hepatic circulation in children.

Adolescent↗
PubMed1991

Expression of ClpB, an analog of the ATP-dependent protease regulatory subunit in Escherichia coli, is controlled by a heat shock sigma factor (sigma 32).

Escherichia coli K-12 produces at least two ATP-dependent proteases, Lon (La) and Clp (Ti), the latter consisting of a regulatory subunit (ClpA) and a proteolytic subunit (ClpP). The gene clpB encoding an analog of ClpA had been found at 57 min on the E. coli chromosome. Cloning and examination of novel heat shock promoters led us to identify a major clpB promoter specifically controlled by a heat shock sigma factor, sigma 32 (the rpoH [= htpR] gene product). beta-Galactosidase synthesis from a PclpB-lacZ operon fusion was transiently induced upon temperature shift from 30 to 42 degrees C, and the induction depended on the rpoH function. Chromosomal clpB transcripts also increased upon temperature upshift and were totally absent in the rpoH deletion strain. In the in vitro transcription experiments, the clpB promoter was specifically recognized and transcribed by RNA polymerase-sigma 32. Nucleotide sequencing and determination of mRNA start sites permitted us to identify a major heat shock promoter located upstream of the clpB coding sequence. The results clearly indicate that clpB expression is under direct control of sigma 32. Since ClpP was recently shown to be a sigma 32-dependent heat shock protein, the present finding suggests the possibility that a potential ATP-dependent protease, ClpB-ClpP complex, plays an important role against thermal stress in E. coli.

ATP-Dependent Proteases↗
PubMed1991

Comparison of 1,5-anhydroglucitol, HbA1c, and fructosamine for detection of diabetes mellitus.

To evaluate the use of serum 1,5-anhydroglucitol (AG) levels in screening for diabetes mellitus, we compared the sensitivity and specificity of HbA1c, fructosamine (FA), and AG in 1620 randomly selected subjects in 11 institutions throughout Japan. Most individuals were receiving diet and/or drug therapy for diabetes. Subjects were separated into four groups based on World Health Organization criteria: nondiabetic control subjects, subjects with impaired glucose tolerance (IGT), patients with diabetes, and patients with other disorders without IGT. The overlap of AG values between each group was less than that of HbA1c or FA values. AG levels were significantly correlated with fasting plasma glucose (r = -0.627), HbA1c (r = -0.629), and FA (r = -0.590) levels. If we took 14 micrograms/ml as the normal lower limit, AG level was highly specific (93.1%), and a decreased AG level indicated diabetes mellitus (84.2% sensitivity). According to the selectivity index (sensitivity value times specificity value), AG determinations were superior to both HbA1c and FA measurements for diabetes screening. When combinations of these tests were used, only AG and HbA1c together were slightly better than AG alone. Thus, together with other advantages of AG, e.g., its wide variance with relatively fair glycemic control and the negligible influence of the sampling conditions, AG level has more potential than HbA1c or FA level as a screening criterion for diabetes.

Biomarkers↗
PubMed1991

Basic studies on ursodeoxycholyl-para-aminobenzoic acid for evaluation of intestinal microflora.

A newly synthesized conjugate of ursodeoxycholic acid with para-aminobenzoic acid (PABA) was investigated to determine its suitability for evaluation of enteric bacteria. This compound, PABA-UDCA, was deconjugated by cholylglycine hydrolase to release free PABA, whereas it was completely resistant to deconjugation by pancreatic and intestinal mucosal enzymes. In bacteriologic experiments almost all the microorganisms that split glycocholic acid deconjugated PABA-UDCA. In rat experiments urinary excretions of PABA were measured during 6 h after oral administration of 10 mg PABA-UDCA (PABA-UDCA administration test). Ten control rats excreted 338.5 +/- 13.8 micrograms (mean +/- SE) of PABA; 10 rats with intestinal stagnant loop excreted more (673.6 +/- 70.2 micrograms; P less than 0.01); whereas 10 rats in each of 7 groups pretreated with oral administration of various antibiotics excreted less (P less than 0.001; polymixin B + tinidazole, 14.0 +/- 2.5 micrograms; polymixin B, 224.9 +/- 23.5 micrograms; tinidazole, 42.7 +/- 8.6 micrograms; kanamycin, 50.3 +/- 5.8 micrograms; clindamycin, 57.4 +/- 7.4 micrograms; vancomycin, 70.4 +/- 8.5 micrograms; and paromomycin, 160.4 +/- 16.4 micrograms). This result was reflected by the bacterial mean count of feces. In the PABA-UDCA administration test, after 2 months of feeding with different diets, rats with high-fiber diet (n = 10) excreted less PABA in urine (70.9 +/- 15.9 micrograms; P less than 0.001) than rats on a control diet (n = 10) and a high-protein-high-fat diet (n = 10) (288.9 +/- 34.5 micrograms and 386.7 +/- 61.2 micrograms, respectively). Fecal bacteriologic status was consistently altered. In human volunteers 250 mg PABA-UDCA was tested. Amounts of PABA excreted in urine during 6 h after dosing were 21.11 +/- 2.02 mg in controls (n = 5) and 12.20 +/- 1.01 mg in the group treated with polymixin B plus tinidazole (n = 5; P less than 0.01). No adverse effect was observed. These basic studies indicate that this compound is likely to offer a simple and rapid method for evaluation of the intestinal microorganisms without use of radioisotopes or expensive, special equipment.

4-Aminobenzoic Acid↗
PubMed1991

Stability of vitamin B1 in a commercial multivitamin syrup preparation.

Accelerated stability studies of a commercial vitamin B1 syrup preparation were carried out at 50, 60, 70 and 80 degrees C. The decomposition of vitamin B1 in the preparation followed pseudo-first order reaction kinetics. Apparent decomposition rate constants conformed to the Arrhenius equation. Apparent activation energy and shelf-life at 25 degrees C were estimated to be 24.2 kcal/mol and 3.3 years, respectively.

Dosage Forms↗
PubMed1991

Intracavitary drainage procedure for giant bullae in compromised patients.

Two cases of giant bullae were treated by intracavitary suction and drainage procedure under local anesthesia because of the poor pulmonary function. After staged bullectomy, the patients returned to normal life. The first case was admitted to our intensive care unit (ICU). Tube drainage was performed in the giant bulla of the left lung immediately after admission. One month after recovery from right heart failure and mediastinal shift to the right side, bullectomy was performed using linear stapler. The patient was discharged 20 days later. The second case was admitted with severe dyspnea and bilateral giant bullae were noticed. We performed tube drainage for larger bulla of the left lung under local anesthesia. Two months later, bullectomy was performed on the right side, because the bulla on the left side became smaller and the general condition of the patient improved. The patient was discharged three months later on foot and has since been asymptomatic. Giant bulla is a well-established clinical entity which includes abnormal dilatation of various parts of the tracheo-bronchial tree and other discrete sacs originating from the interstitial portion of the lung. Giant bullae are frequently associated with marked dyspnea and emphysematous symptoms. However, these symptoms depend upon various factors: size, location, valvular mechanism, condition of the contiguous lung parenchyma and the changes that may take place in the intrathoracic pressure.

Aged↗
PubMed1991

Effect of diabetes on the free polyol pattern in cataractous lenses.

To obtain information about the effects of lenticular polyols on the prevention, initial stages, and development of diabetic cataracts, we identified and determined with gas-liquid chromatography or gas-liquid chromatography/mass spectrometry eight polyols in cataractous lenses of non-insulin-dependent diabetes mellitus patients and nondiabetic subjects. In the diabetics' lenses, the concentrations of polyols (e.g., sorbitol, fructose, mannitol, and adonitol) were higher than in the nondiabetics' lenses, whereas the concentration of 1-deoxyglucose was lower. The mean concentration of myo-inositol in lenses of diabetics was lower than that of nondiabetics, but this difference was statistically not significant. The total content of eight polyols in the diabetics' lenses did not differ significantly from that in the nondiabetics. In the lenses of diabetics, the content of glucose correlated positively with that of adonitol, fructose, and sorbitol. In the lenses of nondiabetics, the content of glucose correlated positively with that of mannitol and inversely with that of 1-deoxyglucose and myo-inositol. In diabetics, hemoglobin A1 (%) correlated positively with the concentration of adonitol in the lenses and inversely with the concentration of lens myo-inositol; however, it did not correlate with the concentration of glucose in lenses. Regulation of both the metabolism of lenticular polyols and the pattern of polyols in serum may be necessary for normalizing lenticular polyol content.

Aged↗
PubMed1990

Isothermal and nonisothermal kinetics in the stability prediction of vitamin A preparations.

A nonisothermal method was applied to shelf-life estimation of commercial vitamin A preparations. The usefulness and limitations of the nonisothermal method, as predicted by computer simulation, were validated. Degradation of vitamin A palmitate followed zero-order kinetics, and non-Arrhenius behavior was suggested for the rate constant. The nonisothermal method predicted a higher shelf-life value than the isothermal method for a syrup preparation, and vice versa, for an injection preparation. Analysis of the results suggested that the nonisothermal method provides better estimates of shelf lives than the isothermal method when drug degradation does not follow the Arrhenius equation near ambient conditions.

Chromatography, High Pressure Liquid↗
PubMed1990

Studies of peripheral blood toxic neutrophils as a predictor of coronary risk in Kawasaki disease--the pathogenetic role of hematopoietic colony-stimulating factors (GM-CSF, G-CSF).

Many toxic neutrophils, characterized by cytoplasmic swelling, vacuolization and toxic granulation, can be seen in the acute phase of Kawasaki Disease (KD; mucocutaneous lymph node syndrome). Polymorphonuclear neutrophils (PMNs) of 36 patients with acute and convalescent phase KD were studied with reference to their morphological characteristics. The percentage of toxic neutrophils in the acute phase tended to be higher in the group with coronary artery lesions (CAL) than in the group without CAL. The results suggest that observation of toxic neutrophils in the acute phase of KD may be useful in predicting a high risk of CAL. In vitro cultivation studies of PMNs from healthy persons, in the presence of diverse hematopoietic colony-stimulating factors (CSF), revealed that GM-CSF (granulocyte-macrophage-CSF) and G-CSF (granulocyte-CSF) participated in the induction of cytoplasmic vacuolization of PMNs, and that the healthy PMNs morphologically mimicked peripheral PMNs seen in the acute phase of KD.

Child, Preschool↗
PubMed1990

Statistical evaluation of accelerated stability data obtained at a single temperature. I. Effect of experimental errors in evaluation of stability data obtained.

Accelerated stability data obtained at a single temperature is statistically evaluated, and the utility of such data for assessment of stability is discussed focussing on the chemical stability of solution-state dosage forms. The probability that the drug content of a product is observed to be within the lower specification limit in the accelerated test is interpreted graphically. This probability depends on experimental errors in the assay and temperature control, as well as the true degradation rate and activation energy. Therefore, the observation that the drug content meets the specification in the accelerated testing can provide only limited information on the shelf-life of the drug, without the knowledge of the activation energy and the accuracy and precision of the assay and temperature control.

Drug Stability↗
PubMed1990

Statistical evaluation of accelerated stability data obtained at a single temperature. II. Estimation of shelf-life from remaining drug content.

Accelerated stability data obtained at a single temperature (40 degrees C) is statistically evaluated and the utility of the actual value of remaining drug content observed in the test for estimation of shelf-life is discussed. The distribution of the time required for 10% degradation at 25 degrees C, t90(25), is calculated from the observed drug content, taking the experimental errors into consideration. The probability that the t90(25) is longer than a specified shelf-life, which is calculated from the distribution, is represented as a function of the observed drug content. The probability was found to depend on the experimental errors in the assay and temperature control as well as in the activation energy of degradation (Ea). The relationship between the observed drug content and the shelf-life assured with a certain probability is shown graphically, so that one can reasonably predict the expected shelf-life as a function of Ea if the accuracy and precision of the assay and temperature control are known.

Drug Stability↗
PubMed1990

Epimerization and racemization of some chiral drugs in the presence of human serum albumin.

Epimerization and racemization of carbenicillin, ethiazide, etoposide and oxazepam acetate were examined kinetically in the presence of human serum albumin (HSA). The concentration of both optical isomers of each drug was determined by stereospecific high-performance liquid chromatography. The apparent rate constants of epimerization or racemization and hydrolysis were estimated from the concentration-time data. HSA retarded the racemization of ethiazide and the epimerization of etoposide. The binding of the drugs to HSA may inhibit the attack of hydroxy ion and/or water molecule and thus retard the epimerization and the racemization. HSA accelerated the epimerization of carbenicillin, which is charged at the pH studied. Ion-ion and ion-dipole interactions between carbenicillin and HSA activate the carbenicillin molecule favorable for the attack of hydroxy ion and/or water molecule. The hydrolysis rates of ethiazide, carbenicillin and oxazepam acetate were increased by the addition of HSA. The hydrolysis rate of d-oxazepam acetate enantiomer bound to HSA was twice that of the l-enantiomer, which suggests that the esterase-like activity of HSA is enantioselective. Differences in the binding affinities of the drug's enantiomers to HSA may account for the selectivity.

Chromatography, High Pressure Liquid↗
PubMed1990

Interaction of liposomes with cultured cells: possible involvement of lipid peroxidation in cell growth inhibition.

Systematic analyses of the interaction between liposomes and cells were examined. Liposomes were found to affect the growth of mouse NIH 3T3 cells depending upon their size, net charge, and cholesterol content. Among the charged compounds, stearylamine was the most inhibitory and showed complete inhibition of cell growth at 100 microM. The cholesterol-rich and small unilamellar vesicles were more suppressive compared to the cholesterol-poor and multilamellar ones, respectively. The binding assay of liposomes to the cells showed a positive correlation between liposome binding and the extent of growth inhibition. Suppression of liposome uptake by inhibitors of the cytoskeletal system and energy metabolism were suggestive of an endocytotic mechanism for the cellular uptake of liposomes. The growth inhibitory effect seemed secondary to the intracellular uptake of liposomes, and peroxidation of incorporated lipids would lead to cellular damage. Therefore, it is highly recommended that potential growth inhibitory effects associated with the particular composition and other properties of liposomes should be carefully assessed in any human studies, especially for long-term use.

Animals↗