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Biomedical subjects

S Ida

Publications and source records attributed to S Ida.

At least 55 records · Page 3Linked to original sources
PubMed1994

A naturally occurring single basic amino acid substitution in the V3 region of the human immunodeficiency virus type 1 env protein alters the cellular host range and antigenic structure of the virus.

Human immunodeficiency virus type 1 circulates in vivo as a mixture of heterologous populations (quasispecies). We previously analyzed the quasispecies of the third hypervariable region (V3) in the viral envelope glycoprotein gp120 in an infected individual and found that the species with a basic amino acid substitution (lysine for aspartic acid) at a particular position evolved and became a distinct population within a short period, followed by progression to the typical immunodeficiency stage (S. Oka et al., AIDS Res. Hum. Retroviruses 10:271-277, 1994). In the present study, we examined the biological significance of this amino acid substitution by constructing recombinant viruses with specific point mutations and comparing their replication capabilities in different cell types. The results demonstrated that the single basic amino acid substitution was sufficient to render a virus fully capable of replicating in human T-cell lines under certain conditions. With an acidic amino acid at the position, the virus grew much less fast or did not grow at all in the T-cell lines. Viral neutralization assay and peptide enzyme-linked immunosorbent assays further showed that this amino acid substitution resulted in different recognition by several of the serum specimens from human immunodeficiency virus type 1-infected individuals and thus could alter the antigenic structure. An additional finding worthy of note was that at the terminal stage, the proviral sequences of peripheral blood mononuclear cells and the viral isolates from them were without exception of the late type with the basic amino acid substitution, whereas the early sequence without the substitution was retained as a major subset in the spleen. These results support the notion that basic amino acid substitutions in V3 are a strong predictor of virus tropism and may be relevant to disease progression.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Development of radioimmunoassay for the novel platelet activating factor receptor antagonist, E6123, and its application to pharmacokinetics in laboratory animals.

A direct radioimmunoassay for the determination of E6123, a novel antagonist of platelet activating factor (PAF) receptor, was developed in order to study the pharmacokinetics at low dose. This procedure used [3H]E6123 as the radioligand and an antiserum obtained from rabbits immunized with the hapten covalently bound to bovine serum albumin. M1B, one of the main metabolites of E6123, exhibited cross-reactivity with antisera. But this metabolite had no effect on measurements of E6123, because the amount of M1B in plasma radioactivity after administration of [14C]E6123 to dogs and monkeys was low. The sensitivity limit of this assay was 25 pg/ml of plasma when 0.1 ml of plasma was used and the assay showed good accuracy and high precision. The validity of the radioimmunoassay was demonstrated by comparative analysis of a number of samples after oral and intravenous administration (1.0 mg/kg) by HPLC-UV method (r = 0.972-0.984, slope = 1.0314-1.2143). The pharmacokinetics of E6123 was studied at a dose of 30 micrograms/kg. After intravenous administration, the plasma concentration-time curves in all species fitted a two-compartment model and the terminal half-lives in guinea pigs, dogs and monkeys (both poor and extensive metabolizers) were 4.77, 1.71, 5.34 and 1.07 h, respectively. After oral administration, the maximum plasma concentrations were obtained within 0.83-3.00 h and the half-life for each animal was almost the same as that after intravenous administration. The mean bioavailabilities of E6123 in guinea pigs, dogs and monkeys (poor and extensive metabolizers) were 106.9, 45.7, 59.1 and 22.8%, respectively.

Animals↗
PubMed1994

Nucleotide sequence of a gene for nitrite reductase from Arabidopsis thaliana.

A nitrite reductase (NiR) gene was recovered from Arabidopsis thaliana genomic library by the homology with a cDNA of spinach NiR and sequenced. Based on the comparison with the spinach cDNA, the Arabidopsis NiR gene was concluded to contain 4 exons [exon 1 of 376 bp (beginning with ATG start codon), exon 2 of 355 bp, exon 3 of 289 bp and exon 4 of 741 bp (ending at TGA stop codon)] and 3 introns (intron 1 of 196 bp, intron 2 of 81 bp and intron 3 of 77 bp). This conclusion was confirmed by the analysis using the RT-PCR method. The deduced amino acid sequence of the coding region of the Arabidopsis NiR gene had high similarities with those of NiR genes of other plants including spinach.

Arabidopsis↗
PubMed1993

Pharmacokinetic study of loprinone hydrochloride, a new cardiotonic agent, in beagle dogs.

Pharmacokinetic parameters and bioavailability of a new cardiotonic agent, loprinone hydrochloride, in beagle dogs were determined by measuring plasma levels of loprinone after intravenous bolus and oral administration. The plasma half-life after intravenous administration of loprinone varied among individuals over the range 2.65-15.40 h. The bioavailability after oral administration of loprinone as a solution was 37.1%. Effects of enterohepatic circulation on the time-course of plasma levels after intravenous administration of the drug were also studied in bile-duct-cannulated beagle dogs. The amounts of loprinone and its glucuronide excreted in bile during 8 h after administration were 25.4 and 8.6% of the dose, respectively, indicating the possibility of enterohepatic circulation. The plasma half-life in bile-duct-cannulated beagle dogs was 1.98 h. These results indicate that the variation in the half-life in beagle dogs resulted from enterohepatic circulation and that the true half-life is about 2 h. The relative bioavailability after oral administration of the drug as a powder in a capsule compared with a solution was 95.7%. In addition, the amounts of loprinone and its glucuronide excreted in bile, and the AUC of plasma level after infusion for 30 min into the portal vein in bile-duct-cannulated beagle dogs were similar to those after bolus intravenous administration. These results show that the low bioavailability reflects incomplete absorption.

Administration, Oral↗
PubMed1993

Pharmacokinetics of a new thienodiazepine platelet activating factor receptor antagonist (E6123) in laboratory animals. Is there a metabolic polymorphism in the rhesus monkey?

1. The pharmacokinetics of E6123, a platelet activating factor receptor antagonist, were studied after i.v. and oral administration to rat, guinea-pig, dog and rhesus monkey. Plasma concentrations of E6123 were determined by h.p.l.c. with UV detection. 2. After i.v. dosing (1 mg/kg), the plasma concentration-time curves fitted a two-compartment model. The half-lives for the terminal phases (t1/2) in rat, dog, and guinea-pig showed very little inter-individual variation, but t1/2 in the monkey (n = 4) varied more than four-fold. The distribution parameters were very similar in rat, dog and monkey (Vc and Vss approx. 1.2 and 1.5 l/kg, respectively) but slightly higher values were found in the guinea-pig, which also showed the lowest plasma protein binding. 3. After oral dosing (1 mg/kg), the maximum plasma concentrations were obtained within 0.3-3.0 h in all species. The half-life for each individual animal was almost the same as that after i.v. dosing. The mean bioavailabilities of E6123 in rat, guinea-pig and dog were about 65, 95 and 81%, respectively, but the values for monkey were again highly variable (range 32-99%). 4. The high variability in the monkey was confirmed by i.v. administration to a further 10 animals. The mean half-lives for the terminal phase in extensive metabolizers (EMs) (n = 4) and poor metabolizers (PMs) (n = 10) were approx. 1 and 4 h, respectively. 5. The rank order for total body clearance of E6123 was: rat > monkey (EMs) > dog > guinea-pig > monkey (PMs).

Animals↗
PubMed1993

Metabolic polymorphism of E6123 in rhesus monkey.

1. The metabolic polymorphism of a new thienodiazepine platelet activating factor receptor antagonist (E6123) in rhesus monkey was studied in vivo and in vitro. 2. After i.v. dosing of 14C-E6123, the levels of radioactivity in blood, plasma and red blood cells were higher in poor metabolizers (PMs) with AUC(0-24 h) values which were about 1.3-1.5 times higher than those in extensive metabolizers (EMs). 3. After i.v. dosing of 14C-E6123, radioactivity was excreted rapidly by both EMs and PMs. However, EMs excreted the radioactivity mainly in urine whereas, for PMs, radioactivity was excreted fairly equally in urine and faeces. 4. In vivo and in vitro studies demonstrated that the metabolic polymorphism of E6123 in rhesus monkey is caused by a difference in the hydrolysis of an amide side chain. 5. Our results suggested that there are two types of the enzymes which metabolize E6123 by this route in EMs, but only one type in PMs. 6. The low affinity enzyme in EMs might be the same as the enzyme in PMs, indicating that the metabolic polymorphism of E6123 in rhesus monkey could depend on the existence of a high affinity enzyme.

Animals↗
PubMed1992

[Study on the relationship between toddler temperament and development (second report)--the relationship between toddler temperament and developmental delay].

The purpose of this study is to clarify the relationship between toddler temperament and developmental delay, and to examine whether the result could be adapted to the health practice of mother and child. As the conceptual framework, we used A. J. Sameroff's transactional model. Questionnaires concerning toddler temperament, rearing environment and toddler development were sent to mothers whose children were scheduled to receive 1 year and 6 months child health examinations, and collected 306 responses. We assessed the developmental status of 41 children among the 306 by means of the Japanese edition of the Denver Developmental Screening Test. All 306 children were classified into either the developmental delayed group (30) or the normal group (275). The data analyses were conducted both quantitatively and qualitatively with the following results. Compared with normal children, developmentally delayed children showed these characteristics: (1) The temperamental category scores of adaptability and persistence were higher, indicating low adaptability and persistence. The prevalence of difficult child, slow to warm up (STWU) child and intermediate high child was relatively higher, with STWU child the highest. (2) The score for the rearing environment was lower. (3) There were cases where disagreement between a child's temperament and the mother's rearing behavior had an influence on the child's development. As a conclusion, these results indicate that a child's temperament must be considered developmental and child-rearing counseling in child health examinations.

Child, Preschool↗
PubMed1990

[Detection of Epstein-Barr virus specific IgE antibody].

To confirm the existence and investigate the biological significance of IgE virus-specific antibodies, we studied Epstein-Barr virus (EBV)-specific IgE antibody by enzyme-linked immunosorbent assay with an anti human IgE monoclonal antibody. We detected EBV-specific IgE antibody in sera not only from patients with the EBV associated diseases of infectious mononucleosis and nasopharyngeal carcinoma, but also from patients with bronchial asthma, collagen disease and healthy volunteers. However, there was no significant difference in the titers of IgE antibody specific for EBV among these groups. No significant relationship between the titers of EBV-specific IgG and IgE antibody, or between the titers of EBV-specific IgE and the total IgE levels in the sera was observed.

Adolescent↗
PubMed1990

[Therapeutic efficacy of miconazole on deep-seated fungal infections in the respiratory tract system].

We evaluated the therapeutic efficacy of miconazole (MCZ, Florid-F inj.), a new antifungal agent for parenteral use, in deep-seated fungal infections of respiratory tract system. A daily dose of 400-1,800 mg of MCZ was given intravenously for 12-38 days (mean: 23.4 days) to 7 patients: 2 patients with pulmonary aspergillosis, 1 patient with bronchial aspergillosis, 1 patient with pulmonary candidiasis and 3 patients with candidemia. One additional patient with pulmonary aspergillosis received three instillations of 20 mg of MCZ into the thoracic cavity. The clinical effects were excellent in 1, good in 4 and poor in 3 patients. The efficacy rate was 100% in 5 cases with respiratory fungal infections but 3 cases with candidemia did not respond well to the treatment. Four strains each of Aspergillus sp. and Candida sp. were identified as causative organisms. Seven of the 8 strains were eradicated by administration of MCZ. Side effects observed were irritation and heat in a leg in 1 patient, hyperlipoidemia in 2 patients and eosinophilia in 1 patient. The adverse reactions disappeared after the completion of the therapy. From the above results, we conclude that MCZ is one of the most useful antifungal agents for parenteral use as a first choice on deep-seated fungal infections in the respiratory tract.

Adult↗
PubMed1990

[Imaging diagnosis of protein-losing enteropathy by 99mTc-labeled serum albumin].

Abdominal scintigraphy with intravenous injection of 99mTc-labeled serum albumin was performed in 6 patients with protein-losing enteropathy (PLE) and 3 patients with non-gastrointestinal tract disorders. In 3 out of 6 patients with PLE, abnormal radioactivity was observed in the ileum region 3 hours after injection, and thereafter clear colon image was obtained. In the remaining 3 patients, the colon was visualized 24 hours after injection. On the other hand, in all patients with non-gastrointestinal tract disorders, no abnormal radioactivity was observed in the abdomen until 24 hours after injection. These results indicate that gastrointestinal protein loss could be demonstrated by scintigraphy with intravenously administered 99mTc-labeled serum albumin. In one healthy subject, 99mTc-labeled serum albumin was administered orally and abdominal scintigraphy was performed. Gastrointestinal tract image was only observed and no other image was demonstrated until 24 hours after oral administration. This result suggests that 99mTc excreted into the gastrointestinal tract is not reabsorbed. Therefore, abdominal scintigraphy with 99mTc-labeled serum albumin appears to be a simple and useful method for diagnosis of PLE.

Adult↗
PubMed1989

Spinach ferredoxin-nitrite reductase: characterization of catalytic activity and interaction of the enzyme with substrates.

The steady-state kinetic parameters of the enzymatic reduction of nitrite by spinach ferredoxin-nitrite reductase [EC 1.7.7.1] were measured under anaerobic conditions. The maximum velocity of ferredoxin-linked activity was essentially the same as for the methyl viologen-linked activity of the enzyme. The initial velocity patterns of the oxidation of reduced ferredoxin suggested a sequential reaction scheme by which nitrite and reduced ferredoxin bind to the free enzyme. The binding of nitrite and ferredoxin to the enzyme was also investigated by different spectra produced by the complex formed by the enzyme with the substrates. Nitrite and ferredoxin each gave a 1: 1 complex with the enzyme. The dissociation constant (Kd) of the enzyme-nitrite complex agreed well with the Km value for the ferredoxin-linked activity, whereas the Kd of the enzyme-ferredoxin complex differed from the Km value for the enzyme activity. It was concluded that our preparation of spinach ferredoxin-nitrite reductase differs from both the complex (Mr = 85,000) and the modified (Mr = 61,000) forms of the enzyme reported by Hirasawa et al. [J. Biol. Chem. 262, 12428-12433 (1987)].

Catalysis↗
PubMed1989

Prevention of neonatal HBV infection with the combination of HBIG and HBV vaccine and its long-term efficacy in infants born to HBeAg positive HBV carrier mothers.

Seventy-three infants born to HBeAg positive HBV carrier mothers were protected from neonatal HBV infection with our standard prevention schedule consisting of two doses of HBIG (0,2 mo) and three doses of HBV vaccine (2, 3, 5 mo). In 62 infants who successfully responded to HBV vaccine with a titer of anti-HBs greater than 2(3), anti-HBs titer was monitored for as long as 48 months (25.6 +/- 11.0 mo) and found to decrease as follows: 5.1 +/- 1.7 at 12 mo., 4.5 +/- 1.8 at 18 mo., 4.2 +/- 1.8 at 24 mo., 4.0 +/- 1.6 at 30 mo., 3.7 +/- 1.7 at 36 mo., 3.2 +/- 2.0 at 48 mo. During the follow-up period, eight HBV events (11.9%) were demonstrated: one case showed an increase of anti-HBs, three showed a reappearance of anti-HBc alone, three showed a reappearance of anti-HBc with increase of anti-HBs, and one became a chronic HBV carrier. All infants were further divided into three groups by their maximal response of anti-HBs to HBV vaccine: Group I (greater than or equal to 2(6)), Group II (2(3)-2(5)), and Group III (2(2) greater than or equal to). Group I sustained a higher titer from 12 to 30 months of age and had less HBV events than G-II and G-III. Our study suggests that acquisition of a high titer of anti-HBs is important in long-term prevention of HBV infection as well as in the neonatal period in infants born to HBeAg positive HBV carrier mothers.

Carrier State↗
PubMed1988

The production of tumor necrosis factor-alpha by rat basophilic leukemia cells with triggering IgE receptor.

We evaluated cytotoxic factor released from rat basophilic leukemia cells (RBL) sensitized with anti-ovalbumin (OVA) mouse serum after incubation with OVA. The cytotoxic activity of this factor was completely blocked by anti-mouse tumor necrosis factor-alpha (mTNF-alpha) specific antibody. Therefore, we concluded that by triggering the IgE receptor, RBL could produce and release TNF-alpha.

Animals↗