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Biomedical subjects

S Okada

Publications and source records attributed to S Okada.

At least 919 records · Page 51Linked to original sources

Sex differences in the localization and severity of ferric nitrilotriacetate-induced lipid peroxidation in the mouse kidney.

Male mice are much more susceptible than female mice to acute renal proximal tubular necrosis as well as the carcinogenic effect induced by an iron-chelate, ferric nitrilotriacetate (Fe-NTA). In the present study, iron-promoted lipid peroxidation was analyzed histochemically in frozen kidney sections using cold Schiff's reagent and biochemically by measuring thiobarbituric acid-reactive substance in the kidney. When untreated mouse frozen kidney sections were exposed to ascorbic acid-Fe-NTA (0.8 mM, 0.2 mM and 0.4 mM) in vitro for 40 min and washed, diffuse Schiff positivity was obtained along the proximal tubules, and no sex differences were evident. When non-reduced Fe-NTA (0.2 mM and 0.4 mM) was layered on untreated kidney sections from males, about half of the cortical proximal tubules showed a positive reaction with Schiff's reagent, whereas in females the proximal tubules of the outer stripe of the outer medulla were positive. In an ex vivo study, 30 to 40 min after i.p. injection of Fe-NTA (5 mg Fe/kg), Schiff-positive areas corresponded to those observed in the in vitro non-reduced Fe-NTA study in each sex. However, in males, the positive tubular cells gradually became necrotic, whereas in females the positivity disappeared with time and there was no tubular necrosis. Results of the thiobarbituric acid test were correlated with the above findings. In conclusion, the localization and severity of Fe-NTA-induced lipid peroxidation in the tubules differed between the sexes. We suspect that these results reflect functional heterogeneity in the ability of the tubules to reduce iron.

Animals↗

Transferrin receptors and selective iron deposition in pancreatic B cells of iron-overloaded rats.

Iron overload was produced in Wistar rats by repeated intraperitoneal injections of ferric nitrilotriacetate (Fe(3+)-NTA) for one to six months. Pancreatic tissues from these iron-overloaded rats and untreated controls were examined for insulin (for B cells), glucagon (for A cells), transferrin receptor (TfR), transferrin (Tf) and ferritin (Ft) using immunohistochemical methods, and for iron by histochemical Berlin blue staining. In the islets of iron-overloaded rats, increased Ft staining appeared prior to deposition of Berlin blue-stainable iron, and the staining intensity of Ft and iron was stronger in B cells than in A cells. In the islets of untreated control rats, the staining intensity of TfR was stronger in B cells than in A cells. TfR staining of the islets was weaker in iron-overloaded rats than in the controls. These findings suggest that 1) iron uptake by islet cells in vivo is regulated and mediated by TfR, 2) intracytoplasmic Ft transforms into stainable iron in iron-overloaded rats, and 3) predominance of TfR expression in B cells may result in selective deposition of iron and predispose B cells to damage and diabetes mellitus in iron-overloaded rats.

Animals↗

Mass protection program of perinatal hepatitis B virus infection in Japan and impact of an optional booster vaccination on its efficacy.

We assessed the efficacy of a government-sponsored mass protection program in Osaka, Japan, for perinatal HBV infection in infants born to HBeAg positive HBV carrier mothers. We also evaluated the impact of optional follow-up procedures in such infants, including an evaluation of anti-HBs response and a booster dose of HBV vaccine for poor responders. The results demonstrated that this mass protection program protected 94.4% of the infants from perinatal HBV infection in the Osaka area. However, the proportion of infants with an unprotective level of anti-HBs was higher in the standard group than in the follow-up group both at 1.0 and 1.5 years of age, which was also the case for HBV events. Furthermore, the present study showed that a booster dose of vaccine in poor responders was very effective in promoting an anti-HBs response. In conclusion, we recommend that a follow-up blood test to confirm a response of anti-HBs to HBV vaccine should be performed at 4-8 weeks after the third injection of HBV vaccine in infants born to HBeAg positive HBV carrier mothers. We also recommend that a booster injection of HBV vaccine should be immediately given to poor responding infants who otherwise are at a considerable risk of developing HBV infection in late infancy.

Adult↗

Massive intestinal albumin loss after Fontan operation.

Massive intestinal protein loss was demonstrated and the site of loss determined by abdominal scintigraphy with 99mTc-labeled human serum albumin in a 9-year-old girl following the Fontan operation for pulmonary atresia with intact ventricular septum. Significant activity accumulating in the lower small intestine and moving with its contents into the colon were shown. Her condition may have resulted from intestinal lymphangiectasia, caused by increased central venous pressure. Abdominal scintigraphy with 99mTc-human serum albumin is useful in the diagnosis of protein-losing enteropathy.

Abnormalities, Multiple↗

Prenatal diagnosis of rubella infection by fetal blood sampling.

Prenatal diagnosis of rubella infection was attempted at 21 to 23 weeks of gestation by measuring rubella-specific IgM by ELISA in blood obtained from 16 fetuses whose mothers had been confirmed rubella infection during pregnancy. Specific IgM was detected in 9 fetuses. In 1 case, the time of the appearance of the rash was 20 weeks of gestation and this pregnancy went to term resulting in a healthy baby without clinical evidence of congenital rubella. The remaining 8 patients had their pregnancies terminated, and fetal infection was confirmed by blood tests after the abortion. No specific IgM was detected in the 7 other fetuses. However, in 2 IgM fetal blood negative cases whose mothers had had the rash at 17 and 20 weeks of gestation, the neonates showed positive IgM findings, but were apparently healthy. The reasons for the false-negative findings are discussed.

Adult↗

Comparison of sensitization to ambulation-increasing effects of cocaine and methamphetamine after repeated administration in mice.

The effects of repeated (5 times) subcutaneous administration of cocaine (10, 20 or 40 mg kg-1) and methamphetamine (1, 2 or 4 mg kg-1) at 3-4 day intervals have been compared in mice placed individually into tilting activity cages. A progressive enhancement of the ambulation-increasing effect was noted for 3-4 h after each administration, indicating that sensitization occurred. This occurrence and the existence of an optimal dose producing sensitization were similar for both drugs. However, enhancement of the effect after cocaine progressed rapidly and maximum sensitization was observed earlier than after methamphetamine administration. Moreover, the higher doses of cocaine (40 mg kg-1) caused stereotypies concurrent with preconvulsive signs of short duration that were enhanced by serial administration. In contrast, methamphetamine caused a more progressive enhancement, but stereotypies with no preconvulsive signs were produced by the higher dose (4 mg kg-1). The respectively, effective doses for the development of enhancement suggested that cocaine was less potent than methamphetamine in producing sensitization. Cross-sensitization occurred between both drugs. Thus, sensitization to cocaine was distinct from that to methamphetamine due to differences in its rapidity, intensity, and the presence or absence of preconvulsive changes.

Animals↗

Analysis of the active center of Bacillus stearothermophilus neopullulanase.

The active center of the neopullulanase from Bacillus stearothermophilus was analyzed by means of site-directed mutagenesis. The amino acid residues located in the active center of the neopullulanase were tentatively identified according to a molecular model of Taka-amylase A and homology analysis of the amino acid sequences of neopullulanse, Taka-amylase A, and other amylolytic enzymes. When amino acid residues Glu and Asp, corresponding to the putative catalytic sites, were replaced by the oppositely charged (His) or noncharged (Gln or Asn) amino acid residue, neopullulanase activities toward alpha-(1----4)- and alpha-(1----6)-glucosidic linkages disappeared. When the amino acids corresponding to the putative substrate-binding sites were replaced, the specificities of the mutated neopullulanases toward alpha-(1----4)- and alpha-(1----6)-glucosidic linkages were obviously different from that of the wild-type enzyme. This finding proves that one active center of neopullulanase participated in the dual activity toward alpha-(1----4)- and alpha-(1----6)-glucosidic linkages. Pullulan is a linear glucan of maltotriosyl units linked through alpha-(1----6)-glucosidic linkages. The production ratio of panose from pullulan was significantly increased by using the mutated neopullulanase which exhibited higher specificity toward the alpha-(1----4)-glucosidic linkage. In contrast, the production ratio of panose was obviously decreased by using the mutated neopullulanse which exhibited higher specificity toward the alpha-(1----6)-glucosidic linkage.

Amino Acid Sequence↗

Effect of sho-saiko-to(xiao-chai-hu-tang) on HBeAg clearance in children with chronic hepatitis B virus infection and with sustained liver disease.

We studied the effect of Sho-saiko-to (Xiao-Chai-Hu-Tang) on HBeAg clearance rate (SN rate) in fourteen children with chronic hepatitis B virus (HBV) infection and with sustained liver disease. Seven of fourteen patients (50.0%) became HBeAg negative in the average observation period of 0.47 years(0.2-0.9 years). Four of those seven patients developed anti-HBe. The annual SN rate in the She-saiko-to treated group was apparently higher than the natural annual SN rate (22.7%) of 22 untreated patients retrospectively reviewed from the onset of hepatitis. Sho-saiko-to seemed to promote clearance of HBeAg in children with chronic HBV infection and with sustained liver disease. Sho-saiko-to may be a useful drug for such patients.

Adolescent↗

Phase IV study and post-marketing surveillance of ofloxacin in Japan.

Data derived from phase IV clinical trials of ofloxacin in 13,850 patients show that the incidence of adverse drug reactions was 2.6%. Gastrointestinal symptoms topped other symptoms in order of frequency, followed by neuropsychiatric and hypersensitivity symptoms. On the other hand, we received 155 spontaneous reports on ofloxacin adverse reactions, including severe convulsions and shock. Examination of various cases of adverse drug reactions suggested that both severe renal dysfunction and a predisposition to epilepsy were risk factors contributing to the onset of convulsions, and a predisposition to allergy was also a risk factor in hypersensitivity reactions including shock. Data from phase IV trials aimed at efficacy analysis show a high efficacy rate. The usefulness of ofloxacin was confirmed by the data obtained after its marketing.

Clinical Trials as Topic↗

Effect of reticuloendothelial blockade on tissue distribution of 99mTc-labeled synthetic liposomes in Ehrlich solid tumor-bearing mice.

The effect of a reticuloendothelial blockade was examined on the tissue distribution of 99mTc-labeled synthetic liposomes prepared from N,N-didodecyl-N alpha-[6-(trimethylammonio)hexanoyl]-L-alaninamide bromide (N+C5Ala2C12) in Ehrlich solid tumor-bearing mice. While a pre-dose of unlabeled phosphatidyl choline liposomes (natural liposomes) hardly influenced the tissue distribution of N+C5Ala2C12 liposomes, the pretreatment of dextran sulfate depressed the uptake in liver accompanied by increasing that in tumor and other tissues except the stomach. However, the extent of liver depression of N+C5Ala2C12 liposomes by dextran sulfate was lower than that of natural liposomes and the pre-dose of unlabeled natural liposomes had a minor effect on the tissue distribution of N+C5Ala2C12 liposomes compared with that of natural liposomes. In the liver uptake of N+C5Ala2C12 liposomes, it was suggested that Kupffer cell phagocytosis was not the main mechanism.

Animals↗

Radical-promoting "free" iron level in the serum of rats treated with ferric nitrilotriacetate: comparison with other iron chelate complexes.

Iron plays a critical role in the production of activated oxygen species and the activity of chelated iron in the biological system depends on the chemical forms of the chelators. In the present study, we used ferric nitrolotriacetate (Fe-NTA, molar ratio of iron to chelators = 1:3), ferric ethylenediaminetetraacetate (Fe-EDTA, 1:3 complex) and ferric Desferal (Fe-Des, 1:1.1 complex) to see their "free" iron content in aqueous solutions in vitro and in the serum obtained after a single intraperitoneal injection of the chelates to rats (7.5 mg of iron/kg). "Free" iron was measured by the bleomycin-assay system. When Fe-NTA was dissolved in water, "free" iron increased linearly with total iron concentration up to 10 microM, whereas Fe-EDTA and Fe-Des showed no "free" iron with corresponding iron concentrations. When these three ferric chelates were dissolved in normal rat serum, "free" iron in Fe-NTA increased abruptly between 40 microM and 60 microM iron concentrations, then increased slowly up to 100 microM. Fe-Des did not show any "free" iron at comparable iron concentrations. Fe-EDTA had an intermediate "free" iron level in the serum. Among the ferric chelate complexes, Fe-NTA showed a much faster increase of and a higher content of "free" iron in the serum than the other two complexes after a single injection of the chelates into rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Complement activation pathways associated with islet cell surface antibody (ICSA) derived from child patients with insulin-dependent diabetes mellitus (IDDM).

We studied the pathways of complement activation associated with the islet cell surface antibody (ICSA) obtained from sera of 7 patients (age less than 15 years) with insulin dependent diabetes mellitus (IDDM). The target cells were 51CR labelled rat islet cells and the complement source was human AB serum. Complement-dependent antibody mediated cytotoxicity (CAMC activity) was obtained using the percentage of cytotoxicity. CAMC activity of untreated sera was significantly inhibited by treating with EGTA or EDTA (p less than 0.001). The CAMC activity of EDTA-treated sera was significantly lower than that of EGTA-treated sera (p less than 0.001). In the inactivated human AB serum, it was lower than that of EGTA-treated sera (p less than 0.05), but not different from that of EDTA-treated sera. These results show that the complement activation associated with ICSA in patients occurred not only via the classical pathway but also via the alternative pathway.

Antibody-Dependent Cell Cytotoxicity↗

[Effect of careful tooth-brushing instruction by teachers on incipient gingivitis in school children].

At the Hiraizumi Primary School in Iwate Prefecture, 84 children with incipient gingivitis were selected at the annual dental examination in May. And the teachers instructed these children individually how to remove the remaining dental plaque. Moreover, the children were checked for the cleanliness of the teeth and inflammation of the gingiva by the teacher or their parents three times a day during the one week just before the second examination. In July the second examination was held and it was revealed that in sixty-three of eighty-four selected children the incipient inflammation of gingiva had improved.

Age Factors↗

[Studies on caries of Ishibashi rat--I. Dental caries in Ishibashi rat].

Ishibashi rats (ISR), which have been demonstrated to be excellent experimental animals for congenital vertebral anomaly, are often observed to develop extensive dental caries even when maintained with the conventional diets instead of any caries-producing diets. In this study, dental caries produced in the ISR fed the conventional diets, commercial pellets, was examined and the location and severity of the lesions were compared with those of the albino rats fed the same diet. The results were as follows: 1. Although no caries was detected up to 100 days of age, 70-100% of the ISR of 101 days and over in age had carious teeth. In the albino rats, only 7-30% had carious teeth. 2. The severity of the carious lesions was much greater in the ISR than in the albino rats. 3. Only the mandibular molars were attacked by the dental caries, and the lesions occurred most frequently in the second fissure of the second mandibular molar both in the ISR and the albino rats. Extensive destruction of the crowns of the ISR second mandibular molars were observed in some specimens, but such destruction was not observed in the specimens of the albino rats. These results suggested that the ISR were susceptible to dental caries, and the development of the dental lesions of the ISR seemed to be rapid compared with that of the albino rats.

Animals↗

[Studies on caries of Ishibashi rat--II. Streptococcus mutans population in oral cavity].

Previously, it was demonstrated that extensive carious lesions occurred in the Ishibashi rats (ISR) while they were bred with conventional diets. In this study, specimens from the oral cavity of the ISR were examined for the presence of Streptococcus mutans, and its occurrence and population were compared with those of the Wistar rats. The results were as follows: 1. S. mutans was first found in the mouth of the ISR when the first molars erupt. 2. The number of S. mutans (CFU on the gelatin agar) and its mean percentage of the total streptococci (CFU on the gelatin agar/CFU on the M-S agar) in the mouth of the ISR increased rapidly during the few days after weaning, and this increment was comparable to that of the Wistar rats fed caries-producing diets, 6PMV, after weaning. However, the population of the S. mutans remained low in the mouth of the Wistar rats fed conventional diets. 3. In the aged ISR, the number of S. mutans and its mean percentage of total streptococci were also much higher than in the aged Wistar rats. These data suggested that the ISR harboured increased the number of S. mutans strains in the oral cavity when compared with the Wistar rats.

Age Factors↗

[Cholecalciferol Reference Standard (Control 901) of the National Institute of Hygienic Sciences].

Cholecalciferol Reference Standard for the Japanese Pharmacopoeia (JP RS) was prepared. The following analytical data were obtained: melting point 85.8 degrees C; UV and IR spectra were in agreement with both of the previous JP RS and USP RS of Cholecalciferol; absorptivity at 265 nm E1%lcm = 476; optical rotation [alpha]20D = + 110.1 degrees; no impurities were detected by TLC and HPLC analyses; assay 100.1% by HPLC against the USP RS. Based on the above results, the raw material was authorized as the Reference Standard of the National Institute of Hygienic Sciences.

Cholecalciferol↗

[Ergocalciferol Reference Standard (Control 901) of the National Institute of Hygienic Sciences].

Ergocalciferol Reference Standard for the Japanese Pharmacopoeia (JP RS) was prepared. The following analytical data were obtained: melting point 118.4 degrees C; UV and IR spectra were in agreement with both of the previous JP RS and USP RS of ergocalciferol; absorptivity at 265nm E1%lcm = 467; optical rotation [alpha]20D = 103 degrees; no impurities were detected by TLC and HPLC analyses; assay 100.1% by HPLC against the USP RS. Based on the above results, the raw material was authorized as the Reference Standard of the National Institute of Hygienic Sciences.

Chromatography, High Pressure Liquid↗