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Biomedical subjects

Y Kusumoto

Publications and source records attributed to Y Kusumoto.

At least 73 records · Page 4Linked to original sources

Changes in HBsAg carrier rate in Goto Islands, Nagasaki Prefecture, Japan.

Annual mass examinations in an area where hepatitis B virus (HBV) infection is very prevalent revealed that 12.1% of inhabitants born during 1946-50 were positive for hepatitis B surface antigen (HBsAg), compared with only 0.6% of those born during 1971-75. To find out why the HBV carrier rate has fallen, changes in the modes of HBV infection were examined. The HBsAg positivity rate among mothers who gave birth to HBV carrier children in 1965 and before was 26.8% and that for such mothers whose babies were born in 1966 and after was 66.7%, whereas the HBsAg positivity rate among children born to HBV carrier mothers in 1965 and before and in 1966 and after were 30.8% and 28.3%, respectively. None of the 503 inhabitants who had no HBV markers in 1976 had become carriers by 1981. These findings indicate that the decrease in the prevalence of HBV carriage is caused mainly by the reduction in occurrence of horizontal transmission of HBV in infancy.

Adolescent↗

Bacteroides gingivalis-specific serum IgG and IgA subclass antibodies in periodontal diseases.

The level of serum IgM, IgG and IgA antibodies including IgG1, IgG2, IgG3, IgG4, IgA1 and IgA2 subclass-specific antibodies to Bacteroides (Porphyromonas) gingivalis fimbriae and to lipopolysaccharide (LPS) were analysed in patients with different forms of periodontal disease (PD) and control subjects by ELISA. Among PD subjects, sera obtained from adult periodontitis (AP), rapidly progressive periodontitis (RPP) and gingivitis contained high titres of fimbriae-specific IgG antibodies (7500-15,000 ELISA units) followed by IgA (90-700 units) and IgM (30-90 units). In contrast, sera from localized juvenile periodontitis (LJP) subjects exhibited much lower titres of fimbriae-specific IgG (89 +/- 11 units), IgA (31 +/- 5 units) and IgM (17 +/- 3 units) antibodies. A similar response pattern was also seen in sera from normal subjects aged 35-41 years who practice normal oral hygiene, while sera of younger adults (aged 18-24) with superior hygiene did not have any antigen-specific antibodies. Analysis of IgG subclass anti-fimbriae responses revealed that the major response was IgG3 followed by IgG1, IgG2 and IgG4 in AP, RPP and gingivitis. Although lower, a similar pattern of IgG subclass titre was seen in LJP and normal subjects aged 35-41 years. When IgA subclass responses were measured in AP and RPP, higher titres of the fimbriae-specific response were noted with IgA1 when compared with IgA2. However, lower but approximately equal levels of fimbriae-specific IgA1 and IgA2 titres were seen in other PD groups. When anti-B. gingivalis LPS-specific responses were measured, the sera of AP patients contained high levels of IgG antibodies (2265 +/- 224 units) followed by IgA (411 +/- 90 units) and IgM (214 +/- 56 units). Further, IgG anti-LPS responses were mainly IgG2 followed by IgG4, IgG3 and IgG1. For IgA subclass responses, higher titres of anti-LPS-specific antibodies were noted in IgA2 subclass over IgA1. These results showed that higher anti-B. gingivalis antibody responses occur in PD when compared with healthy individuals and protein and lipid-carbohydrate antigens of B. gingivalis induce distinct patterns of antigen-specific IgG and IgA subclass responses.

Adolescent↗

Humoral immune response to Bacteroides gingivalis fimbrial antigen in mice.

Bacteroides gingivalis fimbrial antigen incorporated into liposomes, but not in Tris-HCl buffer, significantly raised the levels of anti-fimbriae antibodies in serum, particularly of the IgG class, after oral primary and booster immunizations in BALB/c mice. An approximately linear relationship was observed between the dose of fimbrial antigen and the level of fimbriae-specific antibodies produced; antibody production reached its maximum at an immunization dosage of 500 micrograms of fimbriae per mouse. Fimbriae-specific antibody production was enhanced by use of a semi-synthetic adjuvant, a stearoyl derivative of sodium beta-N-acetylglucosaminyl-(1----4)-N-acetylmuramyl-L-alanyl-D-isoglutaminyl-(L) - stearoyl-(D)-meso-diamino-pimelic acid-(D)-amide-D-alanine (GM)-53) in liposomes. High anti-fimbriae antibody levels in serum and saliva were maintained for several months in the mice that had received two orally administered boosters of fimbrial antigen with GM-53 in liposomes. Salivary anti-fimbriae antibody levels, particularly of the IgA class, were markedly raised.

Administration, Oral↗

Immunoscintigraphy of human tumors transplanted in nude mice with radiolabeled anti-ras p21 monoclonal antibodies.

Anti-ras p21 monoclonal antibody (RASK-3) was used for immunoscintigraphy of human cancer cell lines in nude mice. Iodine-125-labeled RASK-3 was injected into nude mice with either human colon cancers (FCC-1 or BM-314) or lung cancer (KNS-62). Clear images were obtained in all three cancers 7 days after the injection of antibody. No localization of 125I-labeled control monoclonal antibody was observed. The ratio of tissue/blood radioactivity and % ID/g in the tumor were significantly higher than other organs by Day 8. The specific localization index examined by 131I-RASK-3 and 125I-control monoclonal antibody was also higher in the tumor than in other tissues. In the in vitro study, binding of RASK-3 to tumor cells increased significantly by treatment of cells with either lysolecithin or periodate-lysine-paraformaldehyde, which confirmed the intracellular localization of ras p21. The mechanism by which anti-ras p21 antibodies accumulate in tumor sites could be the necrotic changes in tumor cells or changes in membrane permeability of non-necrotic cells. These results provide a strong rationale for the utilization of ras p21 as a target antigen in the imaging of a variety of human cancers.

Animals↗

Detection of preleukemic state of adult T-cell leukemia (pre-ATL) in HTLV-1 carriers.

The prevalence of the preleukemic state of adult T-cell leukemia (pre-ATL) was studied in Nagasaki prefecture, one of the endemic human T-lymphotropic virus type 1 (HTLV-1) areas in Japan. Pre-ATL cases have the monoclonal proliferation of abnormal lymphocytes, without signs of malignant proliferation or clinical signs and symptoms related to leukemia. HTLV-1 carriers who have monoclonal integration of HTLV-1 proviral DNA may be at high risk of developing ATL. Abnormal lymphocytes with either bilobular or large and chromatin-rich nuclei were found in 63/356 (17.7%) of HTLV-1 carriers among inhabitants. We analyzed DNA of peripheral lymphocytes from 108 carries with abnormal lymphocytes by Southern blot technique. Monoclonal integration of HTLV-1 has been detected in 12 cases (11.1%). These results lead to the conclusion that the prevalence rate of pre-ATL among all HTLV-1 carriers is about 2%. Pre-ATL is presumed to be the clinical stage which precedes ATL, although the possibility remains that the HTLV-1 carrier may develop symptoms of ATL directly, without going through the pre-ATL stage.

Adult↗

[Antibacterial activity of norfloxacin on methicillin-resistant Staphylococcus aureus. Comparison with oral antibacterial agents].

Minimum inhibitory concentrations (MIC) of norfloxacin (NFLX) to 133 strains of methicillin-resistant Staphylococcus aureus (MRSA) isolated from clinical patients were investigated and compared with those of minocycline (MINO), erythromycin (EM), amoxicillin (AMPC), cefaclor (CCL) and fosfomycin (FOM). MIC90 of these drugs were 3.13 micrograms/ml with NFLX, 0.39 micrograms/ml with MINO, greater than 100 micrograms/ml with EM, 50 micrograms/ml with AMPC, greater than 100 micrograms/ml with CCL and greater than 100 micrograms/ml with CCL and greater than 100 micrograms/ml with FOM. MIC distribution patterns with 2 peaks were recognized with EM and FOM. Of 55 strains resistant to all of EM, AMPC, CCL and FOM, 50 and 54 strains were well susceptible to NFLX and MINO, respectively. The present investigation demonstrated relatively potent antibiotic effect of NFLX against MRSA. Considering the safety of NFLX to children which have been confirmed and reported separately, it can be concluded that NFLX is a useful oral antimicrobial drug in the treatment of children with MRSA infections.

Administration, Oral↗

[Pharmacokinetics and clinical studies on cefsulodin in neonates].

Pharmacokinetics and clinical studies on cefsulodin (CFS) were conducted in neonates. 1. MIC's of CFS, sulbenicillin and gentamicin (GM) were determined using 7 strains of Pseudomonas aeruginosa clinically isolated from neonates and maintained as stock cultures. CFS was found to be nearly as active as GM. 2. When CFS 20 mg/kg was administered to a 12-day-old neonate by intravenous bolus injection, serum concentrations were 8.7 micrograms/ml before administration and 51.7 micrograms/ml at 30 minutes, 44.4 micrograms/ml at 1 hour, 38.6 micrograms/ml at 2 hours and 11.1 micrograms/ml at 6 hours after administration. The half-life was 2.5 hours. 3. CFS was administered alone or combination with other drugs to 3 neonates. The drug was clinically effective in 2 cases and slightly effective in another. Bacteriologically, one case was rated as decreased, another as replaced, and the remaining one as unchanged. 4. Neither side effects nor abnormal laboratory values attributable to CFS were found.

Cefsulodin↗

[Pharmacokinetic and clinical studies on cefmenoxime in neonates and premature infants].

Pharmacokinetic and clinical studies on cefmenoxime (CMX) in neonates and premature infants were conducted. The results are summarized as follows. 1. Intravenous administration of CMX at 20 mg/kg, via bolus injection or 1-hour drip infusion, produced at sufficiently high blood concentration. As it is the case with other cephem antibiotics, the half-life varied with age and tended to become shorter with aging. 2. There were intergroup differences in urinary recovery of the drug, but urinary concentrations were generally high. 3. In the clinical evaluation, 12 out of 15 cases which were evaluable for efficacy were rated "excellent" or "good". 4. Side effects were evaluated in 27 cases. A bleeding tendency was found in 1 case, eosinophilia in 1 case, elevated GOT in 1 case, and positive PIVKA II in 4 cases. It is, therefore, concluded that CMX is a highly useful drug for the treatment of bacterial infections in neonates and premature infants.

Bacterial Infections↗

[Conversion of acute leukemia from a T-lymphoid to a myeloid phenotype].

A 7-year-old girl with an acute leukemia was reported whose blasts showed conversion from a T-lymphoid to a myeloid phenotype. At the onset of the disease, the blasts were negative for peroxidase and displayed FAB L1 morphology. Surface marker analysis revealed only CD7 antigen. Although complete remission was achieved, an extramedullary relapse was identified as having a several subcutaneous tumors 15 months later. Tumor cells showed the same marker expression as that of the blasts at the onset. After short term culture without an addition of any differentiation stimulators, the blast cells expressed CD2, CD3, CD4, CD8, and CD25 antigens. The karyotype was 46, XX, t(12; 21) (p11; q22). The intensive chemotherapy and radiation therapy were carried out, however, a hematological relapse occurred 12 months later. At this time, the blasts were strongly positive for peroxidase and expressed HLA-DR and CD33 antigens with disappearance of the CD7 antigen. Chromosome analysis revealed the additional abnormalities (del (7) (p15), -17, +der (17) t (17;?) (p13;?].

Child↗

[The influence of cefpodoxime proxetil on the intestinal bacterial flora].

The influence of cefpodoxime proxetil (CPDX-PR, CS-807), a new oral cephalosporin, on the intestinal bacterial flora was studied in tetra-contaminated mice and in pediatric patients. CPDX-PR dry syrup was administered at a dose of 10 mg/kg once a day for 5 consecutive days to mice contaminated with 4 different species of bacteria: Escherichia coli, Enterococcus faecalis, Bacteroides fragilis and Bifidobacterium breve. No notable changes were observed in fecal viable cell counts except that slight decreases of E. coli counts were observed on the days 3 to 5 after starting administration. The subjects in the pediatric study were 5 children with infections, 3 boys and 2 girls at ages from 1 year 1 month to 6 years 10 months, with their body weights ranging from 9.3 to 23.8 kg. CPDX-PR dry syrup was administered at a dose between 3.0 to 3.7 mg/kg, 3 times a day for 4 to 7 days. Although some variations of the fecal bacterial flora were noticed between subjects during the administration of CPDX-PR, no notable changes were observed in major aerobic and anaerobic bacteria such as Enterobacteriaceae, Enterococcus, Bacteroides and Bifidobacterium in 4 of the 5 cases. Large decreases in Streptococcus, Enterobacteriaceae, Bifidobacterium, Eubacterium and anaerobic cocci and an increase in Enterococcus were observed in the other case. There was no case in which glucose non-fermenting Gram-negative rods and fungi became predominant. Regarding Enterobacteriaceae, transitory bacterial replacement was observed within the genus. Fecal concentration of CPDX during the administration of CPDX-PR was extremely low or below the detectable limit except one specimen from a case in which intestinal bacterial flora showed remarkable changes. From the above, CPDX-PR appears to be a drug with a relatively small influence on the intestinal bacterial flora.

Animals↗

[The influence of cefteram pivoxil on the intestinal bacterial flora].

The influence of cefteram pivoxil (CFTM-PI), a new oral cephalosporin, on the intestinal bacterial flora was studied in tetra-contaminated mice and in pediatric patients. CFTM-PI in fine granular form was administered at a dose of 10 mg/kg once a day for 5 consecutive days to mice contaminated with 4 different species of organisms: Escherichia coli, Enterococcus faecalis, Bacteroides fragilis and Bifidobacterium breve. No remarkable change was observed in the fecal viable cell count except that slight decrease in E. coli count was observed on days 2 to 5 after starting administration. The subjects in pediatric study were 5 children, 3 boys and 2 girls at ages from 6 months to 10 years 4 months, with infections. Their body weights ranged from 3.5 to 28.0 kg. CFTM-PI in fine granular form was administered at each dose of 3.0 to 3.8 mg/kg, 3 times daily for 5 to 11 days. During the administration of CFTM-PI, there were some variations in the change of the fecal bacterial flora noticed between subjects. Although Enterobacteriaceae tended to decrease and Enterococci tended to increase, other main aerobes and anaerobes were almost unchanged in most cases. There was no case in which glucose non-fermenting Gram-negative rods and fungi became predominant. In a 10 years 4 months old boy, the fecal concentration of CFTM, the active form of CFTM-PI, was 72.20 micrograms/g and a remarkable decrease of total anaerobe count was observed. In feces, CFTM-PI and CFTM were detected in 4 and 2 cases respectively, and their concentrations were 1.50 approximately 89.65 micrograms/g and 2.25 approximately 72.20 micrograms/g, respectively. beta-Lactamase activities in feces were positive in all cases. From the above, CFTM-PI is considered to be a drug with relatively less influence on the intestinal bacterial flora. But as high concentrations of drugs were detected in feces under some circumstances, we need to pay attention to fecal drug concentrations.

Animals↗

Cytology and arrangement of enterochromaffin (EC) cells in the human stomach.

Serotonin containing enterochromaffin (EC) cells in the human gastric mucosa were observed using serial semithin sections immunostained by Sternberger's PAP method and reconstructed by computer-assisted methods. In oxyntic glands, EC cells displayed a marked pleomorphism which suggests their plasticity or active movement. They sometimes possessed multipolar cytoplasmic processes directly contacting the neighboring epithelial cells and/or gastric lumen. In the antropyloric glands, they are exclusively the "closed-type," which fails to contact the lumen, and are often arranged touching other EC cells (cluster formation), apparently exhibiting polynuclear enterochromaffin syncytia. This syncitium-like arrangement is interpreted as the morphological counterpart of a possibly synchronized function of these cells. The morphological differences of EC cells in their shape, luminal endings and arrangement between both regions may be indicative of regional differences in their functions. Furthermore, the present study provides the first three-dimensional visualization of EC cells in the human stomach.

Chromaffin System↗

[Pharmacokinetics and clinical efficacy of imipenem/cilastatin sodium in neonates].

Clinical pharmacology and clinical efficacy and safety of imipenem/cilastatin sodium (IPM/CS), a beta-lactam antibiotic with a carbapenem nucleus and a dehydropeptidase-I inhibitor, were investigated in newborns. 1. Peak serum concentrations of IPM/CS at a dose of 20 mg/20 mg/kg were achieved at the end of 60-minute infusion. Maximum serum levels of IPM and CS were 44.2 micrograms/ml and 70.0 micrograms/ml, respectively, in neonates with ages 0-3 days. IPM and CS peak levels in premature infants with ages 0-3 days were 47.2 micrograms/ml and 56.1 micrograms/ml, respectively. IPM and CS peak levels in neonates 4 day-old or older were 35.0 micrograms/ml and 41.5 micrograms/ml, respectively, and in premature infants of similar ages were 45.7 micrograms/ml and 65.3 micrograms/ml, respectively. 2. Mean serum half-lives of IPM and CS in 0-3 day-old neonates were 1.6 hours and 3.1 hours, respectively, and the mean serum half-lives in premature infants were 2.1 hours and 4.6 hours, respectively. In neonates 4 day-old or older, the mean serum half-lives of IPM and CS were 1.6 hours and 2.6 hours, respectively, and in premature infants they were 1.5 hours and 1.9 hours, respectively. 3. A dose response was evident between doses of 10 mg/10 mg/kg and 20 mg/20 mg/kg of IPM and CS. 4. Urinary recovery rates of IPM for the 0- to 6-hour post IPM/CS infusion period ranged between 27.2 and 46.6%. For CS, urinary recovery rates for the 0- to 6-hour post IPM/CS infusion period ranged between 25.3 and 100.8%. 5. Clinical efficacy was evaluated in 9 patients and 7 patients showed excellent or good responses. 6. Of 14 patients who received IPM/CS treatment, 1 patient showed hematuria, leukopenia and thrombocytopenia, and 3 patients showed eosinophilia. However, these adverse reactions improved after the completion of therapy. 7. IPM has excellent antimicrobial activity against aerobic and anaerobic Gram-positive and Gram-negative bacteria. In this study, coadministration of IPM and CS produced good clinical responses and no serious adverse reactions. It is hence concluded that IPM/CS sodium is very useful for the treatment of severe bacterial infections in neonates, especially in the presence of beta-lactamase resistant strains and in polymicrobial infections.

Absorption↗

[Influence of sultamicillin on intestinal bacterial flora].

Effects of sultamicillin (SBTPC) fine granules, a new oral beta-lactam antibiotic, on the intestinal bacterial flora were studied in tetra-contaminated mice and in pediatric patients. SBTPC was administered at a dose of 100 mg/kg once a day for 5 consecutive days to mice contaminated with 4 different species of organisms: Escherichia coli, Enterococcus faecalis, Bacteroides fragilis and Bifidobacterium breve. In all of the 4 species, bacterial populations in feces were markedly reduced on days 4 to 5 after the start of the treatment. Subjects in the pediatric study were 5 children with bacterial infections (4 boys and 1 girl) at ages from 1 year 3 months to 10 years 8 months and with their body weight ranging from 11.8 kg to 35.0 kg. SBTPC fine granule was administered at a dose of 10 mg/kg 3 to 4 times a day for 4 to 7 days. Although there were some variations in the fecal bacterial flora noticed among these subjects during the treatment, populations of main aerobes and anaerobes such as Enterobacteriaceae, Enterococcus, Bacteroides and Bifidobacterium decreased markedly in all cases. These decreases were more pronounced for anaerobes and total numbers of anaerobes were markedly reduced in all cases. Glucose non-fermenting Gram-negative rods and fungi tended to increase with administration of SBTPC fine granule. Although these changes tended to return to pre-dosing state after the cessation of the treatment with SBTPC fine granule, attention must be paid to possible occurrences of diarrhea, superinfection or bleeding tendency when treatment with the drug is continued for a long period of time. Fecal concentrations of both ampicillin and sulbactam during SBTPC fine granule treatment showed relatively high values except 1 sample with a high beta-lactamase activity in feces. These high concentrations suggest the possibility of biliary excretion of absorbed drugs and the possibility of hydrolysis of SBTPC in the intestine due to high pH. Fecal concentrations of the drug also appeared to be closely related to beta-lactamase activity in feces.

Ampicillin↗

[Pharmacokinetic and clinical evaluations on ceftriaxone in neonates and premature infants].

Ceftriaxone (CTRX) was clinically evaluated and its pharmacokinetics studied in neonates and premature infants, and the results obtained are summarized as follows. 1. Average blood levels of CTRX after intravenous administration of 10 mg/kg in 3 neonates with birth weights of 2,500 g or more were 45.32 mcg/ml at 15 minutes, 28.91 mcg/ml at 1 hour, 15.76 mcg/ml at 6 hours, and 16.28 mcg/ml at 12 hours, and the half-life was 9.93 hours. The half-life in a newly born premature infant (less than 1 day) was 28.90 hours, and in a premature infant 6 days old it was 12.90 hours. 2. Average blood levels after intravenous administration of 20 mg/kg to 2 neonates aged 0 and 3 days with birth weights of 2,500 g or more, were 129.7 mcg/ml at 15 minutes, 60.94 mcg/ml at 1 hour, 32.04 mcg/ml at 6 hours, and 24.23 mcg/ml at 12 hours, and the half-life was 8.95 hours. The half-life in a newly born premature infant (less than 1 day) was 20.70 hours. 3. Urinary recovery rates of CTRX in 12 hours after intravenous administration of 10 or 20 mg/kg to 6 neonates aged 0 to 3 days (including premature infants) ranged from 13.8 to 50.6%. 4. Clinical efficacies of CTRX were excellent or good in 3 of 4 neonates including infants suspected of having infections (efficacy rate: 75%). 5. As a side effect, diarrhea was noted in 1 case.

Bacterial Infections↗