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Biomedical subjects

R Fujii

Publications and source records attributed to R Fujii.

At least 181 records · Page 10Linked to original sources

[Studies on the dynamics of insulin secretion and the regulatory mechanism of insulin receptor in fetal rats].

In order to clarify the onset of insulin secretion and the regulatory mechanism of its receptor induction in fetus, blood glucose, serum insulin and its hepatic receptor in situ in fetal rats (D18-D21) were measured and the changes of the levels of insulin and its receptor after the direct injection of glucose (1g/kg) to fetal rats in utero were investigated. In fetal rats (D18-D21), both serum insulin and glucose levels increased as pregnancy progresses and specific binding of insulin in fetal liver microsomal membranes increased on D21 of gestation, mainly due to the increase in binding affinity rather than binding capacity. After the direct injection of glucose to the fetus in utero, the rapid increase in serum insulin and the rapid decrease in insulin specific binding to liver microsomal membranes were observed in a part of D20 and all of D21 fetal rats, which was mainly due to the decrease of binding capacity. This suggests that the acute elevation of endogenous insulin level followed by the decrease of insulin specific binding in fetal rat liver is based on the down regulation mechanism of insulin receptor, because the amounts of insulin separated from liver microsomal membranes were less than one twentieth of the insulin concentration which are enough to decrease the binding capacity of hepatic receptor theoretically. In addition, the dissociation of 125I-insulin from liver microsomal membranes of glucose-treated rats were indistinguishable from that of control. From these results, it can be concluded that the onset of glucose-stimulated insulin secretion appears in fetal rats on D20 of gestation and the elevation of endogeneous insulin rapidly down-regulates the number of hepatic insulin receptor in fetal rats.

Animals↗

Cloning of human neuroblastoma cells in methylcellulose culture.

An in vitro methylcellulose technique was used in an attempt to culture neuroblastoma cells from 25 bone marrows from eight children with neuroblastoma. Colonies appeared within 5 days in histologically positive bone marrows. Light microscopy, linearity study, and marker study provided evidence for the neuroblastoma origin of the colonies. These colonies could be distinguished from other colonies under the inverted microscope because of its distinct feature. In one case, the characteristic morphology of neuroblastoma was shown in 3 days of culture, while histological evidence is absent. The diagnosis of neuroblastoma was confirmed by subsequent catecholamine determination. All histologically negative specimens formed no colonies, while all positive specimens formed more than three colonies. Potential application of this culturing technique for monitoring of bone marrow involvement and differential diagnosis in children with neuroblastoma is presented.

Bone Marrow↗

Antibody response to enteric adenovirus types 40 and 41 in sera from people in various age groups.

A total of 322 single and paired serum samples from children (newborn to 10 years old), young adults (18 to 20 years old), pregnant women and their cord serum samples, and elderly people (more than 70 years old) was tested for antibodies to enteric adenovirus types 40 and 41 by neutralization test. Serum samples were also tested for antibody to the common antigen of adenovirus by enzyme immunoassay. The incidence of antibodies rose gradually through childhood. Antibodies were found in 20% of children between 1 and 6 months old and in 50% of those 37 to 48 months old. Of serum samples from young adults, 48% had antibodies. Antibodies were found in 10% of serum samples from the aged. Of patients with acute gastroenteritis, 19% showed a significant rise in antibody to adenovirus type 40 or 41 or both, and 42% of the same serum samples had a significant rise in antibody to rotavirus by enzyme immunoassay. None of the serum samples tested was negative to adenovirus common antigen.

Acute Disease↗

Autologous bone marrow transplantation in acute lymphoblastic leukemia following in vitro treatment with monoclonal antibodies and with complement: analyses for two cases of failure.

Two children with acute lymphoblastic leukemia (ALL) received autologous bone marrow transplantation (BMT) using remission bone marrow treated in vitro with the monoclonal antibodies, CD24 (BA-1), CD9 (BA-2) and CD10 (BA-3), and with rabbit complement. In one child with second remission ALL, hematopoietic recovery after BMT was prompt but, 81 days after BMT, isolated central nervous system (CNS) relapse occurred. Bone marrow relapse developed three months later, and she died 11 months after BMT. In patients with CNS leukemia prior to BMT, as in the present case, more intensive pretransplant CNS treatment and/or a conditioning regimen may reduce the risk of relapse. In the other patient, with primary refractory ALL in first remission, marrow reconstitution was slower. The patient developed interstitial pneumonitis with pleural effusion, and died 54 days after BMT. No infectious causes could be detected by culture or from serological studies of the pleural effusion. The rationale for applying autologous BMT to children with second remission ALL and first remission refractory ALL is discussed.

Antibodies, Monoclonal↗

[Comparative, controlled study on an ampicillin suppository (KS-R 1) with an oral form of ampicillin in urinary tract infections].

Subjects were in-patients with bacterial urinary tract infections, ranging in age 4 months to 11 years 4 months. As a rule, daily dose was either four 125 mg (in potency) suppositories or four 125 mg (in potency) oral form given at 6-hour intervals over a period of 5 days. The number of children subjected to this study was 105. These children were divided into 2 groups (suppository 54; oral form 51) with matched pretreatment background factors. Therapeutic effectiveness rates were 70.4% for the suppository and 66.7% for the oral form, and no significant difference was observed between the 2 groups. Rates of efficacy by severity, presence or absence of underlying and/or complication diseases, daily dose and causative microorganisms did not differ significantly between the 2 groups. There was no significant difference in time-courses of improvement of clinical signs and symptoms between the 2 groups. Eradication rates for causative microorganisms were 65.9% for the suppository and 62.5% for the oral form. Most frequently isolated causative microorganisms were Escherichia coli and Proteus mirabilis. No significant differences were recognized in the therapeutic effect and usefulness evaluated by physicians in charge. The frequency of side effects did not differ significantly between the suppository group (6 with diarrhea and 1 with anal pain: 12.1%) and the oral form group (5 with diarrhea, 1 with displeasure and 1 with vomiting: 12.7%). Abnormal laboratory findings appeared in 6 cases (2 with eosinophilia, 2 with increased GOT and 2 with increased GPT) in the suppository group and 7 cases (2 with eosinophilia, 2 with thrombocytosis, 2 with increased GOT and 1 with increased GPT) in the oral form group.

Administration, Oral↗

[Clinical evaluation of flomoxef in children].

Flomoxef (FMOX, 6315-S), a new parenteral oxacephem antibiotic, was evaluated for its safety, efficacy and pharmacokinetics in children. Twenty-six patients with bacterial infections were treated with FMOX. Clinical efficacy rate was 92% and bacteriological cure rate was 85%. Three cases of infections due to methicillin-resistant Staphylococcus aureus were cured with FMOX therapy. No severe adverse reactions or abnormalities of laboratory test data were associated with FMOX therapy, although loose stools and diarrhea occurred frequently (23%). Serum half-lives of FMOX after a single bolus injection of 9 infants and children were 0.77 +/- 0.31 hour and excretion into urine was rapid. From these experiences, FMOX appeared to be a safe and effective antibiotic when used in children with susceptible bacterial infections.

Age Factors↗

[The trend of childhood bacterial meningitis in Japan (1979-1984). Part 3. On the antibiotic therapy and prognosis].

We studied 973 cases of childhood bacterial meningitis from 1979 through 1984 by means of questionnaire. Monotherapy was carried out in 47.9% of patients with case mortality of 10.3%, whereas those treated with 2 and 3 antibiotics revealed higher rates of 15.8% and 13.5%, respectively. Penicillins (PCs) were the most frequently used for monotherapy, and ampicillin (ABPC) accounted for 48.7%, then followed by cephalosporins (CEPs) group V including latamoxef (LMOX) for 26.8%, with fatality rates of 11.0% for the former and 9.6% for the latter. Chloramphenicol (CP) was used in 19 cases, 4 cases were treated with antibiotics other than PCs, CEPs, CP and aminoglycosides (AGs), and no death resulted. Among 418 cases treated with 2 different antibiotics, 241 cases with aminoglycosides (AGs) revealed a case mortality of 22.4%, and remaining 177 cases where AGs was not used showed a rate of 6.8% (P less than 0.05). One hundred and thirty-one cases treated with ABPC with gentamicin gave 29 deaths showing a significantly high mortality of 22.1%. Similar results were obtained for those treated with ABPC with other AGs. Combination of one PCs with another PCs and PCs with CEPs resulted in lower mortalities of 12.5% and 6.1%, respectively and the combination of beta-lactam with non-AGs antibiotics revealed only 4 deaths out of 74 cases, i.e., a case mortality of 5.4%. A gradual decrease of single or combined use of ABPC, mainly with AGs was observed during the survey period and a rapid increase of CEPs V and LMOX therapy occurred after 1982.

Age Factors↗

[Recent trend of childhood bacterial meningitis in Japan (1979-1984). Part 4. A classification of prognosis and antibiotic treatment based on causative agents].

Nine hundred seventy cases of childhood bacterial meningitis treated at 107 institutions in Japan from 1979 through 1984 were studied using questionnaire. The number of cases that underwent antimicrobial monotherapy remained nearly constant during the study period, but cases of therapies with beta-lactam combined with aminoglycosides (AGs) decreased in number and a gradual increase in the use of beta-lactam combined with non-AGs antibiotics including beta-lactam (Non AGs) was observed. A trend showing decrease in case fatality rate (CFR) was observed except that CFR for Gram-positive bacterial infections treated with beta-lactam + AGs remained at a same level. Cases treated with antibiotics were classified into 3 groups according to major etiological pathogens. Cases with Staphylococcus aureus gave a poor prognosis, among 27 total cases, CFR was 28.6% (2/7) with monotherapy, 50.0% (6/12) with beta-lactam + AGs and 37.5% (3/8) with beta-lactam + Non AGs (P less than 0.1). Among 100 cases of group B Streptococcus (GBS), CFR was 20.0% as a whole, 17.3% (9/52) for monotherapy and 34.5% (10/29) for beta-lactam + AGs (P less than 0.1). Among 198 cases of Streptococcus pneumoniae, CFR was 12.1% as a whole, and was 12.3% (18/146) with monotherapy. CFR for the cases treated with beta-lactam + AGs was 20.8% (5/24) and with beta-lactam + Non AGs was 3.6% (1/28) (P less than 0.1). CFR for 292 cases of Haemophilus influenzae meningitis was fairly low, and was 6.1% (9/148) with monotherapy, 7.4% (5/68) with beta-lactam + AGs and 3.9% (3/76) with beta-lactam + Non AGs, thus very slight differences were observed among the 3 groups of treatment. Among 111 cases of Escherichia coli, monotherapy and beta-lactam + Non AGs gave 6.5% (2/31) CFR, and 5.6% (1/18) CFR, respectively, whereas beta-lactam + AGs showed CFR of 19.4% (12/62), demonstrating a significant difference tendency (P less than 0.1). Similar tendencies were observed in the cases of Listeria monocytogenes, Proteus mirabilis, Pseudomonas aeruginosa and Enterococcus faecalis. Contrary to the high CFR observed with the beta-lactam + AGs treatment, significantly low CFR was frequently obtained in cases treated with a combination of penicillins with cephalosporins including latamoxef or beta-lactam with chloramphenicol. Infections with GBS, E. coli, and P. mirabilis occurred largely in the age between 0 to 6 months and CFR was especially high in the very young.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

[Fundamental study of amikacin in the newborn].

Amikacin (AMK) is one of the aminoglycoside antibiotics, derived from kanamycin A. It has a broad spectrum against Gram-negative rods but its usefulness is mainly in the efficacy against Gram-negative rods which do not respond to commonly used kanamycin and gentamicin. The efficacy and the safety of AMK have been confirmed in children and mature babies. In the trial reported here, we evaluated AMK in newborn. 1. AMK was administered to 13 mature and 8 premature babies via intramuscular injection or intravenous drip infusion for 30 minutes or 1 hour and its blood concentrations were determined. These administrations resulted in blood concentrations 4.47-9.67 mcg/ml with dosage levels 2.3 mg/kg (mean 6.92 +/- 1.66 mcg/ml), 5.86-26.1 mcg/ml with 5-6 mg/kg (mean 15.4 +/- 4.63 mcg/ml) and 27.5-37.7 mcg/ml with 7.5 mg/kg (mean 31.0 +/- 4.76 mcg/ml). Blood half-lives were 1.88 to 9.66 hours, showing longer half-lives in younger subjects. 2. Exchange transfusion (150-180 ml/kg) was performed in 5 mature babies and the variation of blood concentrations of AMK was studied. The study showed that blood concentrations of AMK after the exchange transfusion were 25.6-41.5% (mean 32.3 +/- 5.4%) of the levels detected before the transfusion.

Amikacin↗

[Pharmacokinetics and clinical effects of aspoxicillin in pediatric patients].

Since the efficacy and the safety of aspoxicillin (ASPC, TA-058) have been established on adult patients and the need of ASPC use on pediatric patients was anticipated, we performed a 16 center study on the clinical utility of ASPC in pediatric patients. 1. Pharmacokinetics ASPC was intravenously administered to 45 patients at a dose of 10, 20 or 40 mg/kg by one shot. Serum concentrations of ASPC were dependent of dose levels, and maximum levels of 58.4-230.8 micrograms/ml and half-lives (beta) of 1.08-1.16 hours were observed. Urinary recovery rates were 62.7-67.2% in 6 hours. Results obtained upon drip infusions (0.5-1 hour) were similar to one shot injections. 2. Clinical results (1) Clinical effectiveness Of 318 evaluable patients including 175 boys and 143 girls, 18.2% were nurslings and 61% were young children under 4 years of age. One hundred eighty six patients from whom causative organisms were isolated were classified as A group. Among them were 5 patients suffered with sepsis, but the ASPC treatment eradicated all the bacteria but Salmonella java in 1 case. All of 4 patients with meningitis were cured and all causative organisms (3 cases with Haemophilus influenzae and 1 case with Gram-positive coccus) were eradicated. Cure rates were 90% for 130 patients with respiratory tract infection, 88.6% for 35 with urinary tract infection, 85.7% for 7 with skin soft tissue infection and 89.8% for all the A group patients. Meanwhile, no causative organisms were isolated from 132 patients (B group patients) but cure rate of 91.7% was obtained for this group. No statistical difference was observed between A and B groups. For all the patients (318), the cure rate was 90.6%. (2) Bacteriological effects Of 63 Gram-positive bacteria isolated as pathogens, 58 strains were eradicated. Of 117 Gram-negative bacterial, 101 were eradicated. The eradication rate on all 180 strains was 88.3%. Overall, ASPC showed excellent effects against Streptococcus. Among strains of Staphylococcus aureus, 18 of 20 strains were eradicated. Of 59 strains of H. influenzae, 52 were eradicated and 3 decreased. Among strains of Escherichia coli, 25 of 28 strains were eradicated. Of Pseudomonas aeruginosa, 2 strains were decreased and one was unchanged. (3) ASPC was effective in 93.3% of 30 patients with serious infections and 79.2% of 72 patients with underlying diseases. Cure rates for patients with and without underlying disease were significantly different statistically (chi 2: P less than 0.005).(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗