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Biomedical subjects

T Oikawa

Publications and source records attributed to T Oikawa.

At least 271 records · Page 15Linked to original sources

Genetic background of high incidence of spontaneous tumors in BDX rats.

Genetic background of high incidence of spontaneous tumors in BDX rats was investigated with respect to susceptibility to physical or chemical agents and immune response. Percentages of colony forming ability of normal embryo fibroblasts from BDX rats after exposure to various doses of ultraviolet (UV) light, X-rays and Mitomycin C were almost identical to those of cells from control F344 rats. Furthermore, BDX rats showed similar level of rosette forming cells, blastogenic response, and plaque forming cell (PFC) response as compared with WKA rats used as a control, although BDX rats showed higher natural killer (NK) cell activity. These results indicate that high incidence of spontaneous tumors in BDX rats is not due to some defects in DNA repair or immune response. In 3 methylcholanthrene (MCA) carcinogenesis, however, BDX rats developed tumors very early; the mean latency periods for development of MCA-induced tumors were 135 days in BDX rats and 256 days in F344 rats. Measurement of the inducibility of specific aryl hydrocarbon hydroxylase (AHH) activity in liver microsomes revealed that BDX rats showed higher inducibility than F344 rats: the inducibilities were 23.7 in BDX rats and 5.7 in F344 rats. Higher inducibility of AHH in BDX rats seemed to be parallel to earlier development of tumors in MCA-carcinogenesis in the rats. Thus, it is most likely that high incidence of spontaneous tumors in BDX rats is due to high susceptibility to some chemical carcinogens which may be contained in foods or drinking water in a small dose.

Animals↗

[Fundamental and clinical studies on imipenem/cilastatin sodium in pediatrics].

Fundamental and clinical studies were carried out on imipenem/cilastatin sodium (MK-0787/MK-0791) in pediatric patients. The following results were obtained. A total of 238 clinical isolates stocked by our department was employed to determine the minimum inhibitory concentrations (MICs) of MK-0787 against various species of bacteria. The MK-0787 showed strong antibacterial activities against E. coli, Salmonella, Klebsiella, Proteus, Serratia, E. faecalis and S. epidermidis. Somewhat weaker activities were observed against P. aeruginosa and S. aureus. The MK-0787/MK-0791 was drip-infused intravenously into patients over a period of 1 hour, and serum levels of MK-0787 and MK-0791 were determined. At the dose level of 10 mg/10 mg/kg, the mean serum levels of MK-0787 and MK-0791 were 29.9 micrograms/ml and 18.1 micrograms/ml at 1 hour and 3.4 micrograms/ml and 1.3 micrograms/ml at 3 hours, respectively. The half-lives were 0.89 hour for MK-0787 and 0.99 hour for MK-0791. At the dose level of 20 mg/20 mg/kg, the mean serum levels of MK-0787 and MK-0791 were 46.3 micrograms/ml and 45.2 micrograms/ml at 1 hour and 5.5 micrograms/ml and 3.1 micrograms/ml at 3 hours, respectively. The half-lives were 0.97 hour for MK-0787 and 0.83 hour for MK-0791. At the dose level of 40 mg/40 mg/kg, the mean serum levels of MK-0787 and MK-0791 were 104.0 micrograms/ml and 80.9 micrograms/ml at 1 hour and 7.8 micrograms/ml and 5.9 micrograms/ml at 3 hours, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Influence of cefroxadine dry syrup on intestinal bacterial flora].

Influence of cefroxadine (CXD) dry syrup on intestinal bacterial flora was studied in mice infected with 4 species of bacteria, namely, Escherichia coli, Enterococcus faecalis, Bacteroides fragilis and Bifidobacterium breve, and in pediatric patients having infections in the respiratory tract and cutaneous/soft tissues. The results were summarized as follows: CXD dry syrup was administered for 5 consecutive days to mice infected with the 4 species. No considerable changes were observed in levels of bacteria in the feces and in different parts of digestive tracts. Eleven pediatric patients were orally administered with 30-54 mg/kg of CXD dry syrup a day for 7-15 consecutive days. Symptom of diarrhea was noted in 2 patients. Dominant species of the intestinal flora such as E. coli, Bifidobacterium, and Bacteroides sometimes decreased in patients treated with CXD dry syrup. In general, however, decreases in numbers of these bacteria were insignificant. Changes of intestinal flora in patients treated with CXD dry syrup were apparently smaller than those treated with ampicillin and were similar to those treated with cephalexin or amoxicillin.

Animals↗

[Fundamental and clinical evaluation of ceftazidime in neonates and premature infants].

Fundamental and clinical evaluation of ceftazidime (CAZ) were carried out in neonates and premature infants, and the results obtained are summarized below. Serum concentrations of CAZ after administration of 20 mg/kg were satisfactorily high regardless of the route of administration; bolus intravenous injection or 1-hour intravenous drip infusion. Like other cephem antibiotics, half-lives tended to be shorter as day-ages of subject became higher. Although there were some differences in urinary recovery rates between different dosage groups, they were generally high. Clinical efficacy was either excellent or good in all 21 assessable cases. In 23 cases examined for adverse effects, diarrhea was observed in 1 case, and elevation of GOT and GPT, in another case.

Bacterial Infections↗

[Pharmacokinetic and clinical evaluation of ceftazidime in neonates and premature infants].

Pharmacokinetics and clinical efficacy of ceftazidime (CAZ) were evaluated in neonates. The results obtained are summarized below. After a bolus intravenous injection of 20 mg/kg CAZ to neonates, peak serum concentrations ranged 55.1-97.4 micrograms/ml with the mean half-life of 2.26 hours in neonates with birth weight of 2,500 g or more, and 59.3-60.7 micrograms/ml with half-lives ranging from 3.98 to 4.22 hours in neonates weighing less than 2,500 g at birth. In the time-course observation, it was noted that the half-life at 2 days after birth was longer than half-lives observed on 4 and 9 days after birth. Four cases were given CAZ for treatment, and 3 cases for prophylaxis of infections, and the clinical efficacy was either excellent or good in all of the cases. Neither adverse effects nor abnormal laboratory findings were observed except rash in 1 case. Intestinal flora was examined in 5 cases. It was found that the effect of CAZ was less than that of LMOX, although some delay was seen in the growth of intestinal flora. There was no vitamin K deficiency in any of 6 cases examined.

Bacterial Infections↗

[Basic and clinical studies of cefotiam in neonates and premature infants].

The effect of cefotiam (CTM) on neonates and premature infants was examined in basic and clinical studies. Minimum inhibitory concentrations of CTM against 190 clinically isolated strains kept by this department were investigated. This drug was found to have a strong antibacterial effect against Escherichia coli, Klebsiella spp., Proteus mirabilis and Streptococcus agalactiae, Staphylococcus aureus and Staphylococcus epidermidis, although some strains were resistant. The CTM was given to 0-3, 4-7, and greater than or equal to 8 day-old premature infants and neonates by intravenous injection at the dose of 20 mg/kg, and we studied changes in serum CTM levels over time. Mean serum CTM levels were 62.3 micrograms/ml at 15 minutes and 16.4 micrograms/ml at 6 hours after the injection, with the half-life of 3.6 hours, for the 0-3 day-old premature infants. They were 38.5 micrograms/ml at 15 minutes and 10.1 micrograms/ml at 6 hours, with the half-life of 2.9 hours, for the 0-3 day-old neonates. Those levels were 22.5 micrograms/ml at 15 minutes and 2.9 micrograms/ml at 6 hours, with the half-life of 1.9 hours, for the 4-7 day-old neonates, and 51.8 micrograms/ml at 15 minutes and 1.0 micrograms/ml at 6 hours, with the half-life of 1.1 hours, for the greater than or equal to 8 day-old neonates. The CTM was given to 0-3 and greater than or equal to 8 day-old premature infants and neonates by 1-hour intravenous drip infusion at the dose of 20 mg/kg, and changes in serum CTM levels after the infusion were followed. The 0-3 day-old premature infant (there was only one subject) had a peak serum CTM level of 21.0 micrograms/ml 1 hour after the start of the infusion (that is, at the time of its completion), with the level decreased to 8.6 micrograms/ml at 7 hours and the half-life was 5.4 hours. The mean peak serum CTM level in 0-3 day-old neonates were 36.7 micrograms/ml at 1 hour, which decreased to a mean of 7.0 micrograms/ml at 7 hours; the half-life was 2.3 hours.(ABSTRACT TRUNCATED AT 400 WORDS)

Bacterial Infections↗

Establishment of four mouse hybridoma cell lines producing monoclonal antibodies reactive with ras oncogene product p21.

With the use of proteins derived from Escherichia coli cells expressing the v-H-ras gene product as immunogens and an enzyme-linked immunosorbent assay with whole cells for a screening method, 4 BALB/c mouse hybridoma cell lines (rp-12, rp-28, rp-35, and rp-38) were isolated that produced monoclonal antibodies (MoAbs) showing higher reactivity with murine ras gene-activated cell lines than with normal cell lines. All the MoAbs complexed p21ras from the ras gene-activated cell lines in Western immunoblot analysis and demonstrated a binding property of p21ras to guanine nucleotides. The indirect immunofluorescence assay revealed that MoAbs rp-12 and rp-28 stained the murine and human H- or K-ras-activated cell lines, and MoAbs rp-35 and rp-38 not only stained these cell lines but also weakly stained a human N-ras-activated cell line. All these MoAbs stained the murine fibroblast lines with lower intensity, but they did not stain a human fibroblast line. Further, positive reactions with MoAb rp-12 were seen against human melanomas, but there was no reaction against nevi. The rp-12, rp-28, rp-35, and rp-38 antibodies are useful additions to the MoAbs reacting with p21ras reported previously.

Animals↗

Genetic differences between two substrains of NZB mice.

We have compared the NZB/B1NJ (/NJ) and NZB/B1Pt (/Pt) mouse substrains with respect to a number of immunological and biochemical polymorphisms. In agreement with earlier findings by other workers, we detected histocompatibility antigen difference(s) between the two substrains. Serological analysis indicated that /NJ and /Pt expressed the same allotypes of H-2, Thy-1 and Lyt-1 antigens, while they differed for the Lyt-2 antigen. Amongst 15 biochemical polymorphisms, which we assayed, /NJ and /Pt differed for four, namely Pep-3, Mup-1, Gpd-1 and Hbb. In addition, the two NZB substrains differed for the Hc marker (haemolytic complement).

Animals↗

No expression of a Rous sarcoma virus-induced tumor antigen in mammalian cells infected with retroviruses transducing other oncogenes of the src gene family.

Immunization with mouse and rat cells transformed by Rous sarcoma virus (RSV) or by B77 avian sarcoma virus (ASV) induced complete transplantation resistance against an RSV-induced mouse tumor (CSA1M) in syngeneic hosts. In contrast, most of the mice immunized with a Fujinami sarcoma virus-transformed rat fibroblast line (FSV-3Y1), a feline sarcoma virus-transformed cat fibroblast line (FeSV-FEF), an Abelson leukemia virus-infected Balb/3T3 cell line (AbLV-3T3), or an uninfected 3Y1 cell line could not reject the CSA1M. Serologic analysis with the use of a complement-dependent cytotoxicity assay supported the results of transplantation studies. The mouse and rat cells transformed by RSV or B77 ASV expressed a common tumor-specific cell surface antigen (TSSA) detected by syngeneic antiserum against the CSA1M, whereas none of the FSV-3Y1, FeSV-FEF, and AbLV-3T3 cells expressed the TSSA. These results suggest that the common TSSA in the mouse and rat cells transformed by RSV or B77 ASV containing src gene is not shared with mammalian cells infected with retroviruses transducing other oncogenes of the src gene family (i.e., fps, fes, and abl).

Animals↗

[Experimental and clinical studies on BRL 25000 (clavulanic acid-amoxicillin) granules in the pediatric field].

Fundamental and clinical studies have been performed on BRL 25000 (clavulanic acid 1 part-amoxicillin 2 parts) granules in the pediatric field. The antibacterial activities of BRL 25000 and amoxicillin (AMPC) were investigated against clinically isolated and laboratory stocked strains. BRL 25000 was superior to AMPC against strains of E. coli, Salmonella sp. and Klebsiella sp., and similar against Gram-positive cocci. Serum concentrations of AMPC and clavulanic acid (CVA) were measured 0.25, 0.5, 1, 2, 4 and 6 hours after administration of BRL 25000 granules at dose levels of 7.5, 10, 15 and 20 mg/kg. At 7.5 mg/kg peak level of AMPC of 2.69 micrograms/ml was achieved about 2 hours after dosing with a biological half-life of 1.64 hours; corresponding value for CVA was 0.53 micrograms/ml at 1 hour with a T 1/2 of 1.46 hours. At 10 mg/kg, AMPC also peaked after 2 hours (3.82 micrograms/ml) and the T 1/2 was 1.63 hours, whilst for CVA the value was 0.56 micrograms/ml with a T 1/2 of 1.24 hours. Value for AMPC at 15 mg/kg was 5.18 micrograms/ml at 1 hour post dose with a T 1/2 of 1.48 hours, and for CVA 4.01 micrograms/ml at 1 hour with a T 1/2 of 0.89 hour. At the highest dose of 20 mg/kg, AMPC level reached 4.21 micrograms/ml after 2 hours with a T 1/2 of 2.39 hours, and the CVA peak was 1.64 micrograms/ml at 1 hour with a T 1/2 of 1.01 hours. The 6 hours urinary recovery of AMPC and CVA following administration of the BRL 25000 granules ranged from 38-64% and 2-33%, respectively. In the clinical studies, the BRL 25000 granules are administered to 15 cases with pediatric infections and the clinical response was excellent or good in all cases treated (100%). Bacteriological investigation was performed on 13 strains from 12 cases and all strains were eradicated (100%). Regarding side effects, elevation of eosinophil was observed in 1 case and vomiting in 3 cases.

Administration, Oral↗

[Fundamental and clinical studies of ceftizoxime suppositories in the pediatric field].

The fundamental and clinical studies of ceftizoxime suppository (CZX-S) in the field of pediatrics were made, with the following results. The serum concentration of CZX in the CZX-S 250 mg-administered group peaked 6.00-22.5 micrograms/ml during the period of 15 minutes to 1-hour after dosing, and gradually declined thereafter. The half-life was 1.37-3.81 hours. In the CZX-S 125 mg-administered group, the serum concentration peaked 2.25-21.0 micrograms/ml at 15-30 minutes after dosing and decreased with time. The half-life was 0.95--1.84 hours. The 6-hour urinary recovery rate of CZX in the CZX-S 250 mg group was 22.0-47.5%. The 6-hour urinary recovery rate in the CZX-S 125 mg group was 17.2-25.3%. CZX-S was given 12-73 mg/kg/day (divided into 1-3 times) to 7 children with respiratory tract infection etc. who were considered to respond well to the drug. The clinical effectiveness rate was 100% inclusive of "excellent" and "good". The side effect of pain on insertion was encountered in 1 child.

Bacterial Infections↗