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T Koga

Publications and source records attributed to T Koga.

At least 613 records · Page 34Linked to original sources

Effect of increase in macrophage Ia expression on subsequent immune response in vivo.

By the use of a culture supernatant containing a lymphokine capable of inducing Ia-rich peritoneal macrophages in vivo, we investigated the effect of increased macrophage Ia expression on the induction of antibody response to sheep erythrocytes (SRBC) in mice. Peritoneal macrophages from mice injected intraperitoneally (i.p.) with lymphokine 3 and 4 days earlier contained a high proportion of Ia-bearing macrophages without any significant increase in their phagocytic activity for SRBC. In lymphokine-treated mice, slight enhancement was observed in the primary IgG plaque-forming cell (PFC) response only at an early stage after i.p. immunization with SRBC. When primed mice were injected with lymphokine before secondary i.p. immunization with SRBC, the secondary IgG PFC response was greatly enhanced. On the other hand, lymphokine treatment did not affect either the primary or the secondary IgM PFC response. This effect was dependent on both timing of lymphokine injection and route of secondary immunization with SRBC. Secondary immunization via several routes other than the i.p. route never resulted in such an enhanced secondary IgG PFC response. These results suggest that lymphokine-induced Ia-rich peritoneal macrophages, which first encounter the antigen in the peritoneal cavity, play an important role in the modification of the subsequent antibody response.

Animals↗

[Pharmacokinetic and clinical studies of imipenem/cilastatin sodium in the pediatric field].

Pharmacokinetic and clinical studies of imipenem/cilastatin sodium (MK-0787/MK-0791), a newly developed combined antibiotic in a 1:1 ratio, were performed in the field of pediatrics. The MK-0787/MK-0791 was administered to 15 children. Ten and 20 mg/kg doses of MK-0787 were administered by a intravenous drip infusion for 30 minutes to 3 children each. In the remaining 9 cases, MK-0787 doses of 10, 20 and 30 mg/kg were administered to 3 children each by a 1 hour intravenous drip infusion. Levels of MK-0787 and MK-0791 in plasma, urine and urinary recovery rate of the drugs were also determined. In addition, MK-0787/MK-0791 was administered to a total of 29 children; 2 children with bronchitis, 16 with pneumonia, 4 with UTI, 2 with purulent lymphadenitis and 1 child each with tonsillitis, septicemia suspected disease, peritonitis, staphylococcal scalded skin syndrome and osteomyelitis/bacteremia. The average single dose was 15.3 mg/kg of MK-0787 and administrations were performed by 20-60 minutes intravenous drip infusion 3-4 times daily for an average period of 6 days. The clinical and bacteriological effects of this drug were evaluated in these cases and adverse reactions and unusual laboratory findings were also studied in a total of 33 cases including 4 other drop-out cases. Results of these studies were summarized as follows. In 6 children, 3 each who were given doses of 10 or 20 mg/kg, the mean peak plasma concentrations of the drugs were found at the end of the 30 minutes-infusion with values of 35.20 and 74.90 micrograms/ml for MK-0787 and 44.85 and 93.32 micrograms/ml for MK-0791 after the dose of 10 and 20 mg/kg, respectively. The peak plasma levels of MK-0791 were approximately 1.3 times higher than those of MK-0787 and higher peak levels were observed in the groups with larger doses of either drugs. In the 10 mg/kg group, the mean half-lives of MK-0787 and MK-0791 were 0.97 and 0.71 hour, respectively and those values were 0.89 and 0.63 hour, respectively in the 20 mg/kg group. In both group, MK-0787 tended to have longer half-lives than MK-0791. In 9 children, 3 each who were administered doses of 10, 20 and 30 mg/kg by a 1 hour intravenous drip infusion had the highest plasma levels for both MK-0787 and MK-0791 at the end of the infusion.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

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

Single doses of cefotiam (CTM) by bolus injection of 20 mg/kg of CTM were given to 17 neonates and premature babies (11 prematures) and plasma and urine CTM levels as well as urinary recovery rates of CTM were determined. The CTM was also evaluated clinically with regard to therapeutic and protective effects, bacteriological efficacy as well as safety. A mean daily dose of 56.6 mg/kg of CTM was given intravenously in 2 to 4 divided doses for an average of 8 days to 11 neonates and prematures consisting of 1 case with pneumonia, 2 suspected septicemia, 3 urinary tract infections and 5 for prophylaxis against infections. (In the 6 babies evaluated for clinical effects, a mean dose of 59.8 mg/kg/day of CTM was given for an average 9 days). The findings of these studies are summarized below: The mean peak plasma level of 2 cases of 4-7 day-old neonates was 32.3 mcg/ml 5 minutes after injection. The mean AUC was 96.6 mcg X hr/ml, and the mean half-life was 2.12 hours. In 3 of the 4 neonates of 8-14 day-old group, the mean peak plasma level of 55.6 mcg/ml was obtained after 5 minutes. The mean AUC was 63.0 mcg X hr/ml and the mean half-life was 0.82 hour. Compared to the 4-7 day-old group, AUC was smaller and half-life was shorter in this group. In premature infants, plasma CTM levels were determined in 2, 1, 1, 5 and 2 cases of the 0-3, 4-7, 8-14, 15-21 and 22-28 day-old infants, respectively. In the 8-14 day-old group and one of 15-21 day-old group, peak plasma levels were obtained after 15 minutes. Peak plasma levels in the remaining groups, were attained after 5 minutes. Peak plasma levels in the 5 groups were 40.7, 48.4, 33.9, 38.1 and 45.3 mcg/ml, respectively. Mean or individual AUC's obtained after excluding markedly varying values from the respective groups were 122.0, 96.2, 65.2, 72.8 and 60.4 mcg X hr/ml, respectively. With the increasing age, the AUC tended to decrease. Mean or individual half-lives were 2.31, 1.47, 1.28, 1.41 and 0.96 hours, respectively, showing a tendency to decrease with increasing age. In 6 neonates, high urinary levels continued up to 6 hours after administration. Mean 6-hour urine recoveries in the 4-7 and 8-14 day-old groups were 16.6% and 43.0%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Cefotaxime↗

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

Ceftazidime (CAZ) was administered to 24 neonates and premature infants aged 0-31 days in a dose of 10 mg/kg or 20 mg/kg by an intravenous bolus injection, and plasma concentration, urinary concentration and urinary recovery rate during the first 6 hours after the administration were determined. The CAZ was also administered to a total of 43 patients consisting of neonates, premature infants and infants at ages ranging from 0 day to 1 year 9 months (21 suffering or suspectedly suffering with various bacterial infections, and 22 treated for prophylaxis of infections), by intravenous bolus injections in a mean daily dose of 59.6 mg/kg in 2 to 4 divided doses for 9 days on the average. The clinical efficacy, prophylactic effects and bacteriological response were evaluated. Adverse effects of the drug were examined in 65 cases including 22 drop-out cases, and in some of them, abnormal laboratory findings were also examined. The results obtained are summarized as follows: Patients given 10 mg/kg of CAZ were divided into 5 groups on the basis of age: 0-3 days, 4-7 days, 8-14 days, 15-21 days, and 29 days and older, and mean peak plasma concentrations of CAZ were 40.7, 43.1, 37.1, 38.0 and 35.6 micrograms/ml, respectively, at 5 minutes after administration, with no significant difference. Mean AUC values were higher in younger-age groups, i.e. 189.9, 170.8, 159.1, 135.3 and 134.4 micrograms X hr/ml for the 5 different day-age groups, respectively, and mean half-lives of CAZ in plasma tended to be longer in younger-age groups, i.e. 3.16, 3.05, 2.84, 2.44 and 2.43 hours for the 5 groups, respectively. Patients given 20 mg/kg of CAZ were divided into 4 groups also on the basis of age: 0-3 days, 4-7 days, 8-14 days, and 15-21 days, and mean peak plasma concentrations for the 4 day-age groups were 72.9, 73.3, 70.0 and 78.4 micrograms/ml, respectively, at 5 minutes after administration, without any difference among these groups. Mean AUC values were 429.9, 327.3, 279.3 and 302.1 micrograms X hr/ml for the 4 groups, respectively, with the highest AUC in the youngest-age group. Dose response was observed in mean peak plasma concentrations and mean AUCs when 10 mg/kg and 20 mg/kg dose groups were compared for similar day-age patients. Mean half-lives of CAZ in plasma were 4.01, 3.51, 3.00 and 3.07 hours, the longest being in the youngest-age group.(ABSTRACT TRUNCATED AT 400 WORDS)

Bacterial Infections↗

[Effect of S6472 and cefaclor on bacterial flora in adult human feces].

S6472 is a mixture of cefaclor (CCL) granules with gastric-soluble coating and those with enteric-soluble coating at the ratio (in potency) of 4 to 6. With administration of this formulation, a prolonged blood level of CCL is obtained. S6472 and CCL were administered orally to 19 healthy male volunteers between 20 and 27 years of age (mean: 23 years) weighing between 51 and 80 kg (mean: 64.7 kg). Four subjects were given 2 capsules and 5 subjects were given 4 capsules each containing 187.5 mg of S6472, 30 minutes after breakfast and supper for 5 days. Five subjects were given 1 capsule and 5 subjects were given 2 capsules each containing 250 mg of CCL 30 minutes after breakfast, lunch and supper for 5 days. The number of fecal bacteria was examined 5 days before the start of administration, the day of the start of administration, 3 and 5 days after the start of administration, and 3, 5 and 10 days after the end of administration. Concentration of CCL in feces and susceptibility of isolated fecal bacteria (at the inoculum size of 10(6) cells/ml) to CCL were examined. Adverse reactions and the effects on laboratory test values were also checked. In 4 subjects receiving 375 mg of S6472 twice a day, the mean population of E. coli was 10(7)-10(9) cells/g feces on all days of observation. There was no effect on the population of Klebsiella sp., Citrobacter sp. Enterobacter sp. and other Enterobacteriaceae. The mean population of all Enterobacteriaceae was 10(8)-10(9) cells/g feces on all days of observation. The population of other Gram-negative bacilli did not show a consistent change, either. There was no effect on the population of Gram-positive bacteria such as Staphylococcus sp., Enterococcus, sp., Micrococcus sp., and of Candida sp. Among anaerobic bacteria, Bacteroides sp. showed the mean population of 10(10) cells/g feces on all days of examination. C. difficile was isolated from 2 subjects out of 4 at the level of 10(2)-10(3) cells/g feces 5 days after the start of administration and 3 days after the end of administration. However, there was no production of toxin in either of the 2 subjects. In another subject, C. difficile was isolated at 10(2)-10(4) cells/g feces with a toxin titre of 10(-3)-10(-4) 3 and 5 days after the start of administration and 10 days after the end of administration. The total population of anaerobic bacteria was 10(10)-10(11) cells/g feces on all days of examination.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

[Cerebral paragonimiasis with peculiar calcified foci: a case report].

In Japan more than 400 cases of intracranial invasion of Paragonimus westermani have been reported. In recent years, however, because of the decrease of incidence of parasitic disease, erroneous diagnosis is apt to be made. Peculiar but characteristic calcified cystic lesions in chronic stage of cerebral paragonimiasis were described as "soap bubble appearance" in x-rays by Oh in 1968. We report such a case with calcified lesions of soap bubble appearance in plain x-ray films in the right parieto-occipital region. The patient was a 30-year-old man who had generalized convulsive seizures since childhood. CT scan revealed these lesions to have high density in the margin and relatively low density in the center. Recently some cases of cerebral involvement by Paragonimus miyazakii were reported in Japan. The immunoserological tests are most useful for the diagnosis of paragonimiasis. Bithionol administration is the treatment of choice in acute stage. Calcified lesions with positive serological tests in two years after the onset of cerebral signs should be removed surgically, if possible.

Adult↗

Identification and partial purification of a low-molecular-weight growth inhibitor formed by density-inhibited, tumorigenic V79 Chinese hamster cells.

Medium conditioned by exposure to density-inhibited, tumorigenic V79 Chinese hamster cell cultures reversibly inhibited the growth and DNA synthesis of sparse, proliferating cultures, not only of the same cell line but also of the BALB/c 3T3 A31 murine cell line. This species nonspecific inhibitory activity was found to be mediated by the soluble inhibitor produced endogenously by V79 cells at the time of density inhibition. The molecular weight of this inhibitor is approximately 2000, and production of this compound seems to be serum dependent. Partial purification was done by reverse-phase fast protein liquid chromatography. The inhibitory activity was linearly dependent on the concentration in the inhibitory fraction. This partially purified inhibitor did not include lactic acid, a growth-inhibitory metabolite. These data indicate that a growth-regulatory factor is also operant in tumorigenic V79 cells and suggest that growth of neoplastic cells cannot only be explained by an enhanced positive growth potential but rather by the balance between a positive and negative growth potential.

Animals↗

Extrahepatic portal obstruction in adults--report of an autopsy case.

We report the case of a 31-year-old female with extrahepatic portal vein obstruction. At the age of 16 she had developed hematemesis from esophageal varices. Trans-splenic portography failed to demonstrate the portal trunk, but showed instead well developed collateral circulation. She suffered from repeated hematemesis and ascites despite mesocaval shunt operation and resection of the esophagus for varices. Death resulted from gastrointestinal hemorrhage. Her family history revealed a 30-year-old sister with Takayasu's disease. On autopsy, the portal trunk and the portal vein at the hilus were indistinguishable due to proliferation of hyalinized connective tissue. Cavernous transformation was observed at the hilus. Histologically the presence of the portal trunk and the portal vein was confirmed, but they showed marked sclerosis, and were almost occluded by possible organized thrombus. The cavernous transformation consisted of numerous thin-walled vessels, which were also observed in the medium-sized portal tracts in the liver. The peripheral portal tracts showed no obvious narrowing nor occlusion of the portal vein branches, which are factors usually considered to play an important role in the genesis of portal hypertension in idiopathic portal hypertension. Even though the etiology is not clear, the portal trunk obstruction is concluded to be a significant factor in this case contributing to the development of protracted portal hypertension.

Adult↗

Chemical structure and biological activity relationship of bacterial cell walls and muramyl peptides.

The biological activities of the cell walls of bacteria having different types of peptidoglycans, and those of stereoisomers and analogs of muramyl dipeptide (MDP), of N-acetylglucosaminyl-beta(1-4)-N-acetylmuramyl tetrapeptides having different L- and D-amino acids at the COOH-terminus, and of 6-O-acyl-MDPs were examined to elucidate the relationship between structure and activity. Replacement of the L-alanine residue of MDP with glycine and replacement of the D-isoglutamine residue with L-isoglutamine, L-glutamic acid, and D-isoasparagine, but not with D-glutamic acid, caused a marked decrease in the biological activities of the MDP molecule. Test disaccharide tetrapeptides, irrespective of the configuration of COOH-terminal amino acid, showed strong immunoadjuvant activity and stimulation of macrophages, whereas those having COOH-terminal L-amino acids exhibited greater pyrogenicity, induction of acute joint inflammation, and hemorrhagic necrosis at a primed site than those having COOH-terminal D-amino acids. Introduction of an alpha-branched higher fatty acid to the muramic acid residue resulted in the disappearance of pyrogenicity after i.v. injection, an increase of adjuvanticity, and a loss of dependence on administration vehicles. The lack of the immunopotentiating activity (adjuvanticity) in cell walls from group B-type bacterial species was explained by the combined inhibitory effects of the replacement of the L-alanine residue by glycine and involvement of the alpha-carboxyl group of the D-glutamic acid residue in linking with neighboring peptide subunits.

Acetylmuramyl-Alanyl-Isoglutamine↗

[Pharmacokinetics and clinical effects of cefixime in pediatrics].

Pharmacokinetics and clinical effects of cefixime (CFIX), a new oral cephalosporin antibiotic, in pediatric field were investigated. The result obtained were summarized as follows. CFIX (5% granules) was given to each of 5 children twice in a single dose of 1.5 or 3.0 mg/kg in a cross-over trial. The mean peak serum concentration of CFIX was 0.64 micrograms/ml at 4 hours after given the dose of 1.5 mg/kg and 1.15 micrograms/ml at 4 hours after the dose of 3.0 mg/kg. The mean half-life and the mean AUC values were 2.72 hours and 4.10 micrograms X hr/ml, respectively after the dose of 1.5 mg/kg, and 2.77 hours and 8.26 micrograms X hr/ml after the dose of 3.0 mg/kg. The urinary recovery was investigated in 5 children after the dose of CFIX of 1.5 mg/kg and in 4 children after the dose of 3.0 mg/kg. The mean peak urinary concentrations of CFIX and the mean 12-hour urinary recovery rates were 10.6-67.9 micrograms/ml at 2-10 hours and 15.7% after the dose of 1.5 mg/kg, and were and were 6.16-230 micrograms/ml at 2-8 hours and 18.9% after the dose of 3.0 mg/kg, respectively. CFIX was given to 6 children twice in a single dose of 50 mg either in the form of 5% granules or in capsules in a cross-over trial. The mean peak serum concentrations, half-life and AUC values were 1.26 micrograms/ml at 4 hours, 3.09 hours and 9.63 micrograms X hr/ml, respectively after the dose of 50 mg CFIX in 5% granules, and were 1.16 micrograms/ml at 4 hours, 2.87 hours, and 7.82 micrograms X hr/ml, respectively after the dose of 50 mg in capsules. The urinary recovery was investigated in 5 children. The mean peak urinary concentrations and the mean 12-hour urinary recovery rates were 19.1-114 micrograms/ml at 4-10 hours and 15.7%, respectively after the dose of 50 mg in 5% granules, and were 8.16-89.0 micrograms/ml at 4-10 hours and 11.3%, respectively after the dose of 50 mg in capsules. Clinical efficacy of CFIX was investigated in a total of 26 children including 2 with tonsillitis, 2 with acute bronchitis, 2 with scarlet fever and 20 with urinary tract infection. Each of children were given orally a dose of 2.6 mg/kg CFIX 2-3 times a day for 11 days in average.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗

[Effect of cefminox on bacterial flora in human adult feces].

Cefminox (CMNX), a new cephamycin, was administered by one shot intravenous injection twice daily with a dose of 1,000 mg each time for 5 days to seven healthy male volunteers whose ages ranged from 21 to 28 years (mean: 25 years) and body weights were from 60 to 92 kg mean: 72 kg). The effect of the drug on fecal bacterial flora was investigated and the concentrations of the drug in feces were measured on 5th day before the treatment, on 0, 3rd, and 5th day (the final day of the treatment) during the treatment, and on 3rd, 5th, and 10th day after the treatment. Antibiotic susceptibility tests of CMNX, cefmetazole (CMZ) and cefotaxime (CTX) against several strains of organisms isolated from feces of the seven volunteers were performed. Clinical adverse reactions and effect on laboratory examinations were also investigated. The results of the study are described as follows. Among Enterobacteriaceae, populations of E. coli, Klebsiella sp. and Citrobacter sp. temporarily disappeared during the treatment of CMNX. After 5-day-treatment, that of Citrobacter sp. transiently increased and the isolation of Enterobacter sp. increased during treatment and up to 5 days after treatment, while those of Proteus sp., H. alvei, or Serratia sp. did not show a definite change. The mean Enterobacteriaceae population in general was 10(8) to 10(9) cells/g feces, showing almost no variation, on all examination days except 5th day during treatment when these organisms were not isolated from only one subject. No remarkable change was not found in populations of other isolated organisms including Gram-negative bacilli; Aeromonas sp., Pseudomonas sp. and Acinetobacter sp., and Gram-positive bacteria; Staphylococcus sp., Enterococcus sp., Micrococcus sp. and Candida sp. Among anaerobes, the mean population of Bacteroides sp. was 10(10) to 10(11) cells/g feces, showing almost no variation, and C. difficile was not isolated from any subject, however the toxin was detected in samples from 5 of 7 subjects; one subject showed always positive for toxin on all examination days; 1 on 5th day during treatment to 10th day after treatment; 2 on 5th and 10th day after treatment, and 1 only on 10th day after treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Abdomen↗

[Effect of orally administered lenampicillin and ampicillin on bacterial flora in human adult feces].

Newly developed lenampicillin (LAPC) which is a prodrug of ampicillin (ABPC), and ampicillin (as the control) were each administered to 6 healthy male volunteers, aged from 21 to 25 years (mean 22.4 years) and weighing 57-78 kg (mean 67.0 kg) to study the effect of LAPC and ABPC on fecal bacterial flora. Each drug was given orally 3 times daily (after meals) with each dose of 250 mg for five days. Changes of the fecal bacterial flora caused by the antibiotic were investigated by determining fecal bacterial counts on the 3rd day before the treatment, 0 (the start of treatment), 3rd and 5th days (the final day of treatment) during treatment, and 3rd, 5th and 10th days after the treatment. Fecal concentrations of LAPC and the metabolites (ABPC, 2-aminobenzyl penicilloic acid (ABPA) and 5S-ABPA) for the LAPC group and ABPC for the ABPC group were assayed. A single dose of 500 mg of LAPC was administered orally after breakfast to additional 6 healthy male volunteers and concentrations of LAPC, metabolites (ABPC, ABPA and 5S-ABPA) in the entire stool were determined daily for 5 successive days after the administration. Clinical adverse reactions and abnormal laboratory-findings caused by either drug were studied in the 18 volunteers. The results obtained are summarized as follows. In the bacterial flora of the 6 volunteers to whom LAPC was administered (the LAPC group), the number of isolated E. coli showed no tend of decrease. Mean bacterial counts obtained 3 days before the treatment and at the day of the treatment were 10(9) and 10(8) cells/g, respectively. These values were compared to the counts obtained on the 3rd and the 5th days during the treatment and were found to be about 10(2)-folds as high as the latter. The decreased counts observed on the 3rd and the 5th days did not last and counts increased again to similar levels observed before the treatment. Klebsiella sp. was isolated from 1 or 2 samples before the treatment. It was isolated from as many as 5-6 cases with mean bacterial counts of 10(7)-10(11) cells/g during and up to 5 days after the treatment. The frequency of isolation then decreased to 4 cases on the 10th day after the treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗