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Biomedical subjects

T Koga

Publications and source records attributed to T Koga.

At least 631 records · Page 35Linked to original sources

Familial adult T-cell leukemia.

Two siblings who developed adult T-cell leukemia (ATL) are presented. The patient and 7 of 26 healthy family members examined had the serum antibodies against ATL-associated antigens (ATLA). This family study shows that two main routes of transmission of human T-cell leukemia virus (HTLV) may be involved: one is the route from parents to children and the other is horizontal transmission among spouses, especially from husband to wife; the anti-ATLA-positive family is considered to be a high-risk group for ATL.

Adult↗

The relationship between molecular and cellular repair from potentially lethal damage induced by N-methyl-N'-nitro-N-nitrosoguanidine in Chinese hamster V79 cells.

The relationship between molecular and cellular repair from potentially lethal damage (PLD) induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was investigated in exponentially growing V79 Chinese hamster cells. We compared the repair processes by an alkaline sucrose sedimentation analysis and a colony formation assay. MNNG-treated cells were exposed to the conditioned medium (CM) from density-inhibited plateau-phase V79 cell cultures, as a post-treatment for the induction of PLD repair. When MNNG-treated cells were postincubated in CM, cell survival continuously increased for 18 h, and during this period, DNA replication was substantially suppressed. CM did not inhibit the rejoining of the single-strand breaks of parental DNA. Rather, parental DNA fragments sedimented more rapidly when postincubated in CM than in fresh medium. These data indicate that cellular recovery from MNNG-induced PLD increases in proportion to the resealing of MNNG-induced single-strand breaks of DNA during the suppression of DNA replication, suggesting that excision repair is involved in the PLD repair process.

Animals↗

Chemical properties and immunobiological activities of streptococcal lipoteichoic acids.

Lipoteichoic acids (LTAs) were chromatographically purified from crude phenol-water extract of whole cells of some streptococcal species, which included Streptococcus pyogenes Sv, Streptococcus mutans 6715, and Streptococcus sanguis ATCC 10556. Among these, special attention was paid to S. pyogenes LTA for analyses of chemical composition and biological activities. All LTA preparations contained equimolar amounts of glycerol and phosphorus. Chemical analyses showed that S. pyogenes LTA contained glycerophosphate, alanine, glucose, and fatty acids (as palmitic acid) at molar ratio of 1 : 0.1 : 0.1 : 0.25. The crude phenol-water extract and isolated LTA from S. pyogenes Sv were found to be mitogenic for spleen cells of BALB/c and BALB/c (nu/nu) mice, but not for thymus cells of BALB/c mice. The mitogenicity of deacylated LTA (dLTA) was significantly lower than that of LTA. It was also found that various LTA preparations possessed polyclonal B cell activation ability and adjuvant activity both in vivo and in vitro, as demonstrated by using hemolytic plaque assay. LTA, but not dLTA, induced macrophage activation which resulted in tumor cytotoxicity in mice. Limulus lysate activity of S. pyogenes LTA was approximately 1,000 fold lower than that of Escherichia coli lipopolysaccharide. These results indicate that streptococcal LTA possesses various immunobiological activities that modulate lymphoreticular system in vivo and in vitro.

Animals↗

Influence of dietary cis- and trans-fat on 1,2-dimethylhydrazine-induced colon tumors and fecal steroid excretion in Fischer 344 rats.

To investigate the effects of the difference in the geometry of dietary fatty acids on colon tumorigenesis, male rats were fed semipurified diets containing either partially hydrogenated corn oil (trans-monoene fat) or olive oil (cis-monoene fat) at the 10% level and received a single oral dosage of 1,2-dimethylhydrazine (DMH). The difference in the fatty acid composition of dietary fats was confined essentially to the geometrical isomerism of octadecenoate, and the linoleic acid content was made equivalent (2% of total energy). After about 15 mo of feeding, colon tumor incidence in DMH treated rats was nearly the same in both fat groups. Fecal neutral steroid excretion was higher, while the transformation of cholesterol to coprostanol was lower in rats given the trans-fat. There were no marked differences in the excretion and composition of fecal bile acids between two fat groups. Serum cholesterol and tocopherol levels of rats given trans-fat diets tended to be low. The results suggested that the trans-monoene behaves much like the cis-monoene in the incidence of DMH-induced colon tumors, although there were characteristic differences in metabolic events in the intestine.

1,2-Dimethylhydrazine↗

Increase in Ca2+ permeability of intracellular Ca2+ store membrane of saponin-treated guinea pig peritoneal macrophages by inositol 1,4,5-trisphosphate.

Inositol 1,4,5-trisphosphate (InsP3) releases Ca2+ from the non-mitochondrial Ca2+ store site of various types of cells. To study the mechanisms of the Ca2+ release from the store site, the effect of InsP3 on the passive Ca2+ release and influx, and the active Ca2+ uptake in the presence of oxalate, was examined using saponin-treated guinea pig peritoneal macrophages. InsP3 stimulated the passive Ca2+ release and influx. Although InsP3 slightly inhibited the active Ca2+ uptake in the presence of oxalate, it seems unlikely that the Ca2+ release by this agent is caused by the inhibition of the Ca2+ uptake, because the addition of apyrase or hexokinase (which removes ATP within 30 s, so that no more Ca2+ can be accumulated) or vanadate (which inhibits the Ca2+ uptake) resulted in very slow release of Ca2+. These results suggest that the Ca2+ permeability of the Ca2+ store membrane is increased by InsP3. InsP3 did not cause an increase in the Ca2+ permeability of phospholipid vesicles (liposomes), indicating that this agent may bring about Ca2+ release by a specific effect on the physiologically relevant Ca2+ channels or carriers in the non-mitochondrial Ca2+ store site. The passive Ca2+ release by InsP3 was enhanced by ATP and an unhydrolyzable ATP analogue, 5'-adenylyimidodiphosphate, but not by ADP or AMP. The passive Ca2+ release by InsP3 was observed even at 0 degree C.

Adenosine Triphosphate↗

Purification and characterization of glucosyltransferases from Streptococcus mutans 6715.

A water-soluble glucan-synthesizing glucosyltransferase (GTase-S) and a water-insoluble glucan-synthesizing glucosyltransferase (GTase-I) were purified from culture supernatant of Streptococcus mutans 6715 (serotype g) by ammonium sulphate precipitation, chromatofocusing on a Polybuffer exchanger PBE 94 column, and subsequent phenyl-Sepharose CL-4B or hydroxyapatite column chromatography. The GTase-S and GTase-I activities were purified 4019- and 4714-fold, respectively, and the molecular weights were calculated to be 160000 and 165000, respectively. GTase-S had a pH optimum of 5.0, a Km of 8.8 mM for sucrose in the presence of 20 microM-dextran T10, and an isoelectric point of pH 4.3. GTase-I had two pH optima of 5.0 and 7.0, Km values of 4.9 mM (at pH 5.0) and 7.0 mM (at pH 7.0), mM (at pH 7.0), and an isoelectric point of pH 4.9. Methylation analysis indicated that the water-soluble glucan produced by GTase-S was a highly branched 1,6-alpha-linked D-glucan with 1,3-linked glucose residues, and that the water-insoluble glucan synthesized by GTase-I was composed of 1,3-alpha-linked glucose units.

Ammonium Sulfate↗

Chemical and immunological characterization of a novel amphipathic antigen from biotype B Streptococcus sanguis.

A new type of amphipathic antigen was extracted from whole cells of Streptococcus sanguis ATCC 10557 (biotype B, serotype II) by the phenol/water method. The extract was treated with nuclease P1, and was applied to a column of Sepharose 6B. Each fraction was checked by passive haemagglutination (PHA) and immunodiffusion tests against anti-10557 serum which was obtained by immunizing rabbits with whole cells of strain ATCC 10557. Strong PHA activity was demonstrated in the first hexose-containing peak (peak 1) eluted near the void volume, while the second hexose-containing peak (peak 2) produced a heavy band against anti-10557 serum in an immunodiffusion test. The third peak (peak 3) which partially overlapped with peak 2 reacted with concanavalin A, but not with the antiserum, in agar gel. Peaks 2 and 3 had no PHA activity. Peak 1 contained only 1% phosphorus, indicating that cells of strain ATCC 10557 possess an amphipathic antigen which differs from the lipoteichoic acids that are common in many Gram-positive bacteria. Peak 1 was a fatty acid-substituted heteropolysaccharide composed of glucose, galactose, mannose, glycerol and fatty acids in a molar ratio of approximately 1.0:1.3:2.7:0.3:1.0. PHA activity was inhibited in the presence of polymerized mannose. Peak 2 was composed of glucose, galactose, rhamnose and N-acetylgalactosamine in a molar ratio of approximately 1.0:1.4:0.8:0.8, which was essentially identical to the serotype II carbohydrate antigen reported previously.

Antigens, Bacterial↗

Biochemical and immunobiological properties of lipopolysaccharide (LPS) from Bacteroides gingivalis and comparison with LPS from Escherichia coli.

Lipopolysaccharides (LPSs) were isolated from Bacteroides gingivalis and Escherichia coli by the phenol-water and butanol-water procedures. The phenol-water-extracted LPS from B. gingivalis 381 was composed of 46% carbohydrate, 23% hexosamine, 18% fatty acid, and 5% protein. The major component sugars of this preparation were glucose, glucosamine, rhamnose, galactose, galactosamine, and mannose, and their molecular ratio was 1:0.9:0.7:0.6:0.6:0.4, respectively. Neither heptose nor 2-keto-3-deoxyoctonate was detected. The butanol-water-extracted LPS from this strain was composed of 76% glucose, 7% fatty acid, and 13% protein, and it was associated with a number of polypeptides (13 to 56 kilodaltons). The main fatty acid of both LPS preparations was palmitic acid. It was found that biological activities of LPS from B. gingivalis were comparable to those of LPS from E. coli in terms of activation of the clotting enzyme of Limulus amebocyte lysate, mitogenicity, polyclonal B cell activation, and stimulation of interleukin 1 production in BALB/c mice. Furthermore, LPS-nonresponsive C3H/HeJ spleen cells were found to yield good mitogenic responses to both phenol-water-extracted LPS and butanol-water-extracted LPS from B. gingivalis or butanol-water-extracted LPS from E. coli. On the other hand, spleen cells from LPS-responsive C3H/HeN mice responded well to all these LPS preparations.

Amino Acids↗

Acute joint inflammation in mice after systemic injection of the cell wall, its peptidoglycan, and chemically defined peptidoglycan subunits from various bacteria.

The systemic injection of an aqueous suspension of cell wall or its peptidoglycan (PG)-rich sonicate derived from group A streptococcus and Lactobacillus casei induced acute joint lesions in BALB/c, DBA/1J, (BALB/c X DBA/1J)F1, and C3H/He mouse strains, but not in C57BL/6, DBA/2, and AKR strains. Cell walls and their enzymatically degraded PG fragments from other bacteria as well as the synthetic disaccharide dipeptide and Lactobacillus plantarum cell wall-derived disaccharide tripeptide produced similar acute inflammation in susceptible BALB/c mice. Acute swelling and erythema of the ankles and wrists were observed as early as 3 h, reached maximum severity by day 2, and generally subsided by days 4 to 6 after injection. Histological studies showed synovial proliferation, marked infiltration of many mononuclear cells and a few polymorphonuclear leukocytes in the soft tissues, and extensive deposition of fibrinous exudate in the joint space. Antibody response was detectable against the PG fraction. However, anti-PG antibody does not seem to be responsible for the pathogenesis of this disease. On the other hand, experiments on decomplementation by cobra venom factor suggest that complement components are involved in the early phase of this arthritic model.

Animals↗

Characterization of monoclonal antibody specific for human type II collagen: possible implication in collagen-induced arthritis.

We obtained monoclonal antibodies specific for human type II collagen and characterized them using human collagen type I, II, III and V and tropocollagen A (3/4) (TCA) and tropocollagen B (1/4) (TCB) fragments of type II collagen which were obtained by digestion with tadpole collagenase. These antibodies were of the IgG2a class and specific for the conformational determinant of TCA fragment of type II collagen. When injected intravenously into DBA/1J mice, one of the monoclonal antibodies induced arthritis, which was characterized by early onset, mildness in severity and preferential localization mainly in the peripheral joints of the lower extremities. These results suggest that, at least, one of the arthritogenic determinants of type II collagen for collagen-induced arthritis of mice exists in the three quarter region from the N-terminus of type II collagen.

Animals↗

[Fundamental and clinical studies of cefminox in children].

Cefminox (CMNX, MT-141), a newly developed injectable cephem antibiotic, was administered intravenously as one shot injection at 3 different dosages of 10, 20 and 40 mg/kg to 9 children; for each dose level 3 children were used. In these children serum and urinary concentrations as well as recovery rates were determined. In addition, in order to determine clinical and bacteriological efficacies of CMNX, it was used in the treatment of 37 cases of various infections consisting of 2 cases of acute tonsillitis, 1 case of acute tonsillitis associated with otitis media, 1 case of acute bronchitis, 1 case of chronic bronchitis, 20 cases of pneumonia, 1 case of pneumonia associated with otitis media, 8 cases of urinary tract infections, 2 cases of purulent lymphadenitis and 1 case of gluteal abscess. The drug was administered intravenously as one shot injection at a mean daily dosage of 76.6 mg/kg, in 4 divided doses in most cases, for a mean period of 6 days. Finally, in 43 cases added of 6 drop out cases which were included in analysis of efficacy side effects and abnormal laboratory findings were examined. The following results were obtained. In 9 cases, which received CMNX at 3 different dosages of 10, 20 and 40 mg/kg for 3 cases each intravenously as one shot injection, mean serum concentrations reached the peaks of 109.4, 218.1 and 357.1 mcg/ml at 5 minutes after injection, respectively, showing dose response relation. The mean half-lives were 1.74, 1.62 and 1.84 hours, respectively. The mean concentrations of CMNX in urine in the same cases as used for determinations of serum concentrations were highest during the 0 approximately 2 hours period, reaching 1,582, 3,304 and 4,618 mcg/ml at the respective doses. The mean recoveries within the first 6 hours were 82.8, 69.8 and 81.3%, the rate for 20 mg/kg group being lower than those obtained for the other groups. This is possibly due to 1 case which showed unusually low recovery rate of 44.4%. When this case is excluded, the recovery rates became similar for all groups. As to clinical results, responses rated as good or higher were obtained for 91.9% of the cases (34 cases/37 cases), with high efficacy rate. No side effects were seen in 43 cases included of drop out cases.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

[Effect of BRL 25000 (clavulanic acid-amoxicillin) on bacterial flora in human feces].

BRL 25000 (187.5 and 375 mg tablets), a formulation of CVA-K and AMPC in the ratio of 1:2, and AMPC (as control drug) were administered to healthy volunteers, aged 20 approximately 28 years and weighing 60 approximately 85 kg (68.8 kg, on average). Each drug was administered 3 times a day (after meals) for 5 days and the volunteers were separated into 3 groups of 4 subjects each. The effect on the fecal flora was studied before dosage, during administration (day 3 and 5) and day 3 and 5 after the administration course was completed. Studies were undertaken to isolate C. difficile on the last day of administration and 3 and 5 days after administration had ceased. Fecal concentrations and the susceptibility of the isolates to AMPC, CVA-K and BRL 25000 were measured. Side effects and laboratory findings were studied. The results obtained were as follows: 1. In BRL 25000 (187.5 mg X 3/day) group, the population of E. coli was on average, 1 X 10(6) approximately 9 X 10(6) cells/g feces before initiation of administration and it increased by 2 logarithms 3 and 5 days after initiation of administration. By 3 and 5 days after end of administration, the E. coli population was similar to the initial population. The population of Klebsiella sp. was 1 X 10(6) approximately 9 X 10(6) cells/g feces on average before commencement of dosage and it increased by 2 logarithms 3 days after initiation of administration but there was no consistent change in the Klebsiella sp. population thereafter. The Enterobacter sp., population was not consistent neither was the population of other Enterobacteriaceae. In total, the mean Enterobacteriaceae population was 1 X 10(7) approximately 9 X 10(7) cells/g feces before initiation of administration and increased by 2 logarithms 3 days after initiation of administration, and then returned to the initial level 5 days after end of administration. No consistent changes in population were noted for the other Gram-negative bacilli. The Staphylococcus sp. population was 1 X 10(6) approximately 9 X 10(6) cells/g feces on average before initiation of administration. This organism was detected in only 1 case 3 days after initiation of administration and in another 5 days after initiation of administration, thereafter, the population was similar to the initial population.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗

[Effects of KS-R1 (ampicillin suppository) and ampicillin oral dosing on fecal flora of children].

A newly developed product, KS-R1 (a suppository containing 250 mg potency of ampicillin (ABPC)), was given to 7 children (5 boys and 2 girls) ranging from 4 years and 5 months to 8 years and 10 months in age, 3 times a day (average daily dose, 62.4 mg/kg) for 5 days. As a control, the same amount of ABPC dry syrup was given orally to 7 children (4 boys and 3 girls) ranging from 2 years and 8 months to 7 years and 7 months in age, 3 times a day (average daily dose, 55.3 mg/kg) for 5 days. The effects of these 2 preparations on the bacterial flora of the feces were investigated, and concentrations of ABPC in the feces and sensitivities of the isolated strains to ABPC were determined. The results were as follows. As for Gram-negative bacilli in the feces from children given KS-R1, there was no change in Escherichia coli, Klebsiella sp., Citrobacter sp. and Enterobacter sp. which were isolated from many children 3 days after the end of treatment, but they did not show any constant pattern of change in mean number. Other species did not show any pattern of increase in the number of children from whom they were isolated, or in the number of bacteria during the course after the beginning of treatment. The total number of bacteria identified as Enterobacteriaceae was at the level of 10(8) cells/g on any day of examination. Of Gram-negative bacilli other than Enterobacteriaceae, Pseudomonas sp. showed no constant pattern of change in number. On the other hand, of Gram-positive bacteria, there was no constant pattern of change in the number of Staphylococcus aureus, Coagulase-negative Staphylococci began to be isolated from many children 5 days after the beginning of treatment and were isolated from all children 5 days after the end of treatment, but there was no tendency for the mean number to increase. Enterococcus sp. was not isolated from 3 children 3 days after the beginning of treatment, and was decreased in number by one order in 3 out of other 4 children as compared with before-treatment. However, this species was isolated from all children 3 days after the end of treatment, and the mean number of bacteria was similar to that before-treatment although the number of bacteria was different in individual children.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗

[Fundamental and clinical studies on ceftizoxime suppositories in children].

The peak levels of serum ceftizoxime (CZX) after a single rectal administration of CZX-S at doses of 125 and 250 mg in 157 pediatric patients were occurred at 21 approximately 25 minutes in pediatric patients aged less than 1 year and over than 7 years, at 16-20 minutes in 1-3 years patients, at more than 26 minutes in 4-6 years patients. They were 9.45, 9.58, 11.71, 12.43 mcg/ml, respectively. The mean highest levels of serum CZX were 8.56, 10.66, 12.50 mcg/ml after the administration of CZX-S as less than 10.0, 10.1-15.0, 15.1-20.0 mg/kg dose respectively, all of which were occurred at 21-25 25 minutes. A close dose response was observed. The pain of insertion was not observed in any cases. The discharge of melted suppository or defecation after administration was observed in 15.2% of total 184 cases, which was noticed more frequently in the lower aged children. There was no influence by dose. Clinical effects of CZX-S were studied in 72 pediatric patients with various infections. CZX-S was administered rectally at the mean daily dose of 41.0 mg/kg divided into 3 or 4 times for 6 days. Clinical responses were excellent in 46 cases, good in 24 cases, fair in 2 cases. The efficacy rate was 97.2%. Regarding side effects, the pain of insertion was noted in 2 cases (2.8%), diarrhea in 6 cases (8.3%), the elevation of eosinophil in 1 case (1.7%). Bacteriologically, 23 strains (92.0%) out of 25 strains isolated from the patients were eradicated.

Bacteria↗

[Fundamental study on ceftizoxime suppositories in adults and children].

The pharmacokinetics of newly developed ceftizoxime suppository (CZX-S) was studied in healthy volunteers and in children, compared with that of intramuscular CZX and intravenous CZX: In 8 volunteers (aged 19 to 24 years), each of 500 mg (potency) CZX-S containing 3%, 4% and 5% sodium caprate was compared with 500 mg intramuscular CZX and 500 mg intravenous CZX as a single administration in the cross-over method. In addition each of 500 mg CZX-S containing 4% and 5% sodium caprate was studied in 2 groups of 8 volunteers (aged 22 to 24 years) and of 8 volunteers (aged 19 to 27 years); each CZX-S was given 3 times a day successively for 5 days. The pharmacokinetics of 125 mg and 250 mg CZX-S, which contained 3% sodium caprate, were also evaluated as a single administration in 9 children (aged 6 years 4 months to 12 years 0 month) and in 11 children (aged 7 years 8 months to 12 years 4 months), respectively. The irritabilities of CZX-S were studied in all subjects who participated in this trial. The feeling of foreign body, the feeling of defecation, the burning sensation and the pain were evaluated in volunteers; the feeling of defecation and the pain were evaluated in children. The results were as follows: I. Pharmacokinetics in healthy volunteers 1. Given as a single administration The mean peak concentrations of serum CZX were occurred 30 minutes after 500 mg CZX-S containing 3%, 4% and 5% sodium caprate, which were 10.5 mcg/ml, 12.3 mcg/ml and 12.4 mcg/ml, respectively. These values were 1.35 mcg/ml, 1.60 mcg/ml and 1.69 mcg/ml at the conversion unit of 1 mg dose per 1 kg body weight. The mean peak serum CZX concentration of CZX-S containing 3% sodium caprate was slightly lower than that of CZX-S containing 4% or 5% sodium caprate, but was 1.9 times higher than that of the ABPC suppository. There was no marked difference among 3 preparations of CZX-S in mean Tmax and T1/2. Cmax of CZX-S containing 3% sodium caprate was 1.40 mcg/ml at the conversion unit of 1 mg/kg. AUC of CZX-S containing 3% sodium caprate was slightly smaller than that of CZX-S containing 4% or 5% sodium caprate, but 3.1 times that of the ABPC suppository in healthy volunteers. When 500 mg CZX was intramuscularly administered by one shot to 8 volunteers, Tmax was same as that of CZX-S or was slightly later.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗