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T Koga

Publications and source records attributed to T Koga.

At least 721 records · Page 40Linked to original sources

Production of T cell-activating monokine of guinea pig macrophages induced by MDP and partial characterization of the monokine.

The production of T cell-activating factor(s) by macrophages stimulated with muramyl dipeptide (MDP) was studied. By MDP stimulation, a rapid increase in intracellular activity of the T cell-activating factor was induced, which preceded an increase of the activity in the extracellular medium. The rapid appearance of the activity in the cell and that in the medium were both inhibited by cycloheximide or puromycin. These results demonstrated that MDP stimulated rapid production of T cell-activating factors by inducing de novo synthesis of the factors, and that these newly formed factors are rapidly secreted. The activities of intracellular and extracellular secreted factors were both found in high m.w. (50,000 to 90,000) and low m.w. (10,000 to 30,000) fractions by gel filtration. The secreted high m.w. factor migrated as a single peak and did not dissociate into smaller components in SDS-PAGE analysis, indicating that the high m.w. factor is neither a complex of low m.w. factor with other proteins nor an aggregate of low m.w. factors. The properties are similar to those of our previously reported factor that helped antigenic activation of T cells for lymphokine production.

Acetylmuramyl-Alanyl-Isoglutamine↗

An effective fixative for glucocorticoid receptors in fetal tissues.

As a preliminary study in an autoradiographic study of glucocorticoid (GC) receptor localization in orofacial tissues of mouse fetuses, a search was made to determine the most effective fixative for preservation of the GC-receptor complex. Twelve-day-old mouse fetuses were administered tritiated triamcinolone acetonide (3H-TAC) intraamniotically and subsequently processed by one of the following three procedures: freeze-drying, prefixation with Karnovsky's fixative, or "the catechin fixative" (Karnovsky's fixative containing 1% D-catechin) and postfixation with osmium tetroxide. Light microscopic autoradiography and liquid scintillation counting of the specimens revealed that the catechin fixative gave the best results for fixation of the steroid-receptor complex and preservation of tissue structure. Light and electron microscopic autoradiographic studies of the time course of the localization of 3H-TAC in palatal shelves supported the catechin fixative as being the most effective in preservation of GC-receptor or ligand complexes.

Animals↗

Inactivation of D-glucosyltransferases from oral Streptococcus mutans and Streptococcus sanguis by photochemical oxidation.

Cell-free D-glucosyltransferase of D-glucose-grown Streptococcus mutans AHT was completely inactivated in the presence of 0.002% of Methylene Blue at 25 degrees and pH 7.0 after illumination with a 150-W incandescent lamp. The rate of inactivation was decreased at pH values less than 7.0. Histidine was the only amino acid residue modified to a significant extent, and the rates of oxidation of histidine residues and loss of enzyme activity closely agreed. Production of both water-insoluble and -soluble D-glucan fractions from sucrose by the oxidized D-glucosyltransferase preparations was significantly inhibited. Photooxidation with 0.002% of Rose Bengal at pH 7.0 or higher also induced complete inactivation of the D-glucosyltransferase. These results strongly suggest that the imidazole portion of histidine may function as part of the active sites of both D-glucosyltransferase isozymes of S. mutans AHT, which are responsible for the synthesis of (1 goes to 3)- and (1 goes to 6)-alpha-D-glucosidic linkages. The D-glucosyltransferases from S. mutans 6715 and AHT-mutant M1, and Streptococcus sanguis ATCC 10558 were also almost completely inactivated by Methylene Blue-sensitized photooxidation.

Amino Acids↗

[Absorption, excretion and clinical trials of cefroxadine in the field of pediatrics (author's transl)].

A study was made with the newly developed cefroxadine (CXD) dry syrup by measuring the serum level, urine excretion and recovery rate in 10 children who were orally administered 5, 10 and 20 mg/kg at 1 hour after meals and the following results were gained. Also, its clinical efficacies and side effects were investigated in the following cases who were treated with a mean dose of 33 mg/day divided into 3 to 4 portions for a period of 9 days on the average; viz. a total of 151 cases consisting of 9 cases of pharyngitis, 39 of tonsillitis, 11 of streptococcal infection, i.e. scarlet fever, 7 of bronchitis, 6 of pneumonia, 1 of otitis media, 6 of purulent lymphadenitis, 1 of purulent parotitis, 1 of subcutaneous abscess and 3 of impetigo. 1. The serum level tends to reach its maximum level within 1 hour after administration. The mean concentrations of 5, 10 and 20 mg/kg dose in the foregoing time were 6.35, 9.12 and 21.62 mcg/ml respectively and dose response was observed. CXD showed higher concentration than CEX, CED and CFT. The mean half-life periods of the 3 dose were 72, 84 and 66 minutes respectively and variations were observed, but the drugs maintains a satisfactory serum level. 2. The time which showed highest urine excretion was mainly in the 0 to 2 hours bracket and the average concentrations of 5 , 10 and 20 mg/kg dose in the foregoing time were 381.2, 771.7 and 1,577.7 mcg/ml respectively. The dose response was more evident than in the serum concentrations. The average recovery rates within 6 hours were 93.6, 88.3 and 94.3% respectively and they were similar to those of CEX, CED and CFT. 3. The clinical effects were evaluated were in 148 cases out of the total of 151 and 136 cases, or 91.9% showed good or excellent efficacy response. 4. The daily dose groups of less than 30 mg/kg and 31 to 40 mg/kg formed the majority and there was no difference in the comparison of the clinical effectiveness in these 2 groups. Administration of a daily dose of 20 to 40 mg/kg is sufficient for the treatment of the aforementioned mild diseases except for pneumonia. 5. The clinical effects were compared between the 3 and 4 times a day treatment groups, but there was no difference between these two groups with regard to the foregoing daily dose. The 3 times a day treatment is acceptable, but the 4 times a day treatment is preferable when pharmacokinetics if taken into account. 6. The bacteriological effects in 41 cases, or 97.6% out of the 42 cases were above the efficacy base line and a high efficacy rate was achieved. 7. With regard to side effects, diarrhea developed in 4 cases and eosinophilia in 6 cases, abnormal simultaneous increases in GOT and GPT in 1 case and 1 case each for abnormal values in LDH and BUN were seen in the clinical test values. The foregoing results show that CXD has high efficacy and safety and it can be said that it is a drug required in the pediatric field.

Adolescent↗

[Clinical trials of cefroxadine on skin and soft tissue infections in the field of pediatrics (author's transl)].

CXD was administered orally at an average dose of 28.6 mg/kg (18.3 approximately 42.3 mg/kg) for an average 6 days (3 approximately 12 days) to a total of 99 pediatric cases with skin and soft tissue infections (impetigo 89, abscess 7 and furuncle 3) ranging from 3 months to 9 years old. The drug was given twice to 4 times per day after meals. The clinical and bacteriological effects and adverse reactions of CXD as well as the susceptibility of the causative organisms against CXD and CEX were studied, and the results obtained are as described below: 1. According to judgement of the attending doctors, CXD had a high global efficacy rate of 90.9%. 2. Analysis of the attending physicians' evaluations of the clinical effects on impetigo revealed that a dose of CXD 20.5 approximately 30.4 mg/kg t.i.d. can produce satisfactory responses. 3. According to the assessments by Evaluation Committee, the global clinical effects after 3, 5 and 7 days were 81.4, 91.2 and 94.6%, respectively. This indicates that clinical responses increased with prolongation of the treatment period, viz. better responses obtained after 5 and 7 days. This suggests that a minimum of 5 days administration is required for treating these infections. 4. As for impetigo having the largest number of patients in this study, a dose of CXD 20.5 approximately 30.4 mg/kg per day seemed to produce satisfactory clinical effects. 5. As for dose per day, the t.i.d. regimen of CXD 20.5 approximately 30.4 mg/kg seemed to exhibit satisfactory clinical responses, as already mentioned. Because of quite a small number of patients on the q.i.d. regimen of higher doses, however, the question of whether the t.i.d. treatment with 20.5 approximately 30.4 mg is adequate or not should be determined by a comparative study between the q.i.d. and t.i.d. treatments. 6. As for bacteriological responses, a high global effect of 87.1% was obtained with CXD against S. aureus and S. pyogenes isolated from 74 and 1 cases, respectively. 7. As for impetigo with predominant number of cases, CXD was highly effective bacteriologically at a daily dose of 20.5 approximately 30.4 mg/kg t.i.d. As an appropriate comparative evidence with the q.i.d. treatment was lacking, however, therapeutic validity of the t.i.d. treatment could not be determined definitely. 8. Utility was evaluated by the attending physicians on the total 99 cases, and CXD showed as high as 88.9%. 9. There were neither non-compliances nor adverse reactions to this treatment. 10. CXD showed a distribution of antimicrobial activity similar to that of CEX, against 74 isolates of S. aureus with the MICs of CXD ranging from 1.56 to 25 mcg/ml and those of CEX ranging from 0.78 to 25 mcg/ml, with peak MIC being 3.13 mcg/ml for both drugs. As for S. pyogenes, only one isolate from the same species, CXD was antimicrobial activity at 0.2 mcg/ml and CEX was antimicrobial at 0.39 mcg/ml. The above findings suggest that CXD is highly effective against acute skin and soft tissue infections in pediatrics.

Abscess↗

Efficient induction of collagen arthritis by the use of a synthetic muramyl dipeptide.

We developed an efficient method for production of experimental polyarthritis. Native collagen (type II) from human costal cartilage was emulsified with incomplete Freund's adjuvant (IFA) containing the synthetic adjuvant N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP), and injected into one hind footpad of the PVG/c rat. This method reproducibly induced severe arthritis with high incidence, whereas the collagen alone in IFA produced mild arthritis with low incidence. MDP alone in IFA was shown to be minimally arthritogenic under identical conditions.

Acetylmuramyl-Alanyl-Isoglutamine↗

Induction of delayed type hypersensitivity-like skin reaction by peptidoglycans of bacterial cell walls.

Water-soluble glycopeptides isolated from Lactobacillus plantarum and Staphylococcus epidermidis cell walls elicited a delayed type hypersensitivity (DTH)-like skin reaction in rats previously immunized with Mycobacterium tuberculosis cell walls, but not in unimmunized rats. Histological examination of the skin reaction sites in immunized animals revealed a close similarity of this skin reaction to a typical DTH reacton with respect to the time course of development and the types of cells that infiltrated into the skin reaction sites, which were characterized by a predominant infiltration of mononuclear cells at 48 hr. This DTH-like reaction was also demonstrated by immunizing the rats with the cell wall peptidoglycans of L. plantarum or S. epidermidis and skin testing them with homologous as well as heterologous peptidoglycans. The DTH-like reaction appeared to be caused by peptidoglycans that exist in common in the cell walls of phylogenetically distant bacterial species. Furthermore, it was also suggested that the putative antigenic determinants(s) might include both the glycan chain and part of the peptide moieties of the cell wall peptidoglycan rather than either of the single moieties.

Animals↗