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Biomedical subjects

T Koga

Publications and source records attributed to T Koga.

At least 397 records · Page 22Linked to original sources
PubMed1992

A 72-year-old female with adult Still's disease.

We treated a 72-year-old woman with adult Still's disease. The diagnosis was made on the basis of a prolonged, high grade, quotidian fever, polyarthritis, maculopapular skin rashes and exclusion of other possible diseases. A high serum ferritin value was a key factor both in making the diagnosis and in the follow-up. The patient responded to the administration of oral prednisolone at 30 mg/day, which was tapered to 10 mg/day, with no recurrence of symptoms. This disorder can be an important cause of prolonged fever in the elderly as well as in the younger population.

Aged↗
PubMed1992

[Clinical studies on cefprozil granules in pediatric skin soft tissues infections].

Cefprozil (CFPZ), a newly developed cephalosporin in fine granular form, was administered to pediatric patients with skin and soft tissue infections. MICs were determined for 6 drugs including CFPZ, cephalexin (CEX), cefaclor (CCL), ampicillin (ABPC), methicillin (DMPPC), cloxacillin (MCIPC) against 53 clinical isolates of Staphylococcus aureus from these patients. An inoculum size of 10(6) CFU/ml was used in the MIC-determinations. CFPZ was given to 73 patients with ages ranging from 6 months to 10 years and 8 months and 71 cases were evaluable for clinical effects as follows; impetigo (65), Staphylococcal scalded skin syndrome (1), furuncle (1), subcutaneous abscess (3), and periproctal abscess (1). To study clinical efficacy, bacteriological effects and safety of this drug, a mean dose of 8.4 mg/kg with 3-4 daily dosages (57 cases of t.i.d. and 14 cases of q.i.d.) was administered for an average of 6 days. The results obtained are summarized as follows. 1. With regard to the 53 isolates of S. aureus, MICs of CFPZ against 52 strains (98.1%) ranged from 0.78 to 3.13 micrograms/ml. 45 strains (84.9%) were inhibited at 0.78 micrograms/ml. MIC90 of CFPZ was 1.56 micrograms/ml, but MIC against 1 strain of Methicillin-resistant S. aureus (MRSA) was 100 micrograms/ml. The MIC90 of CEX and CCL were 6.25 micrograms/ml and MIC of CEX and CCL against 1 MRSA strain were 200 and 100 micrograms/ml, respectively. The MIC90 of ABPC, DMPPC and MCIPC were 6.25, 3.13 and 0.39 micrograms/ml, respectively. CFPZ showed the second highest activity after MCIPC against S. aureus. 2. CFPZ showed very good clinical responses and clinical effects in 71 patients all of whom judged by doctors in charge as having "good" or better responses. 3. For impetigo patients, the evaluable cases by score 3, 5 and 7 days after administration of the drug were 52, 39 and 20 patients, respectively. The efficacy rates on these days were 90.4, 100 and 100%, respectively. The efficacy rate at a daily dose of 30.1-45.0 mg/kg on day 3 was 17.2% higher than that at 22.5-30.0 mg/kg, and the "excellent" response rate of 30.1-45.0 mg/kg group was 45.3% greater. Because of these results, it is expected that good clinical effects can be obtained at a daily dose of 22.5-30.0 mg/kg of CFPZ, but better responses can be expected at 30.1-45.0 mg/kg in 3-4 divided doses given for 5 days. 4. Bacteriological effects of CFPZ were determined against 60 strains of S. aureus.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗
PubMed1992

[Pharmacokinetic and clinical studies on cefprozil granules in the pediatric field].

Cefprozil (CFPZ), a newly developed oral cephalosporin in a fine granular form for pediatric use, was administered to children with bacterial infections. MICs were determined for 6 drugs including CFPZ, cephalexin (CEX), cefaclor (CCL), ampicillin (ABPC), methicillin (DMPPC) and cloxacillin (MCIPC) against the following 84 strains isolated from cases to which CFPZ was administered; 55 strains of Gram-positive cocci (GPC) including 2 strains of Staphylococcus aureus, 49 strains of Streptococcus pyogenes, 4 strains of Streptococcus pneumoniae, and 29 strains of Gram-negative bacilli (GNB) including 10 strains of Haemophilus influenzae, 18 strains of Escherichia coli, and 1 strain of Proteus mirabilis. MIC determination of these strains was done with an inoculum size of 10(6) CFU/ml. In pharmacokinetic studies, serum concentrations, urinary concentrations and urinary recovery rates were investigated using bioassay and high-performance liquid chromatography (HPLC). CFPZ was orally administered 30 minutes before meals to 9 children with ages ranging from 7 years and 1 month to 12 years and 3 months. Three groups of 3 children were tested with doses of 4.0, 7.5 and 15.0 mg/kg, respectively. In addition to the above, clinical and bacteriological studies were performed in a total of 160 cases consisting of children with ages ranging 5 months to 12 years and 5 months. A mean dose of 8.6 mg/kg in 3-4 divided doses (130 cases of t.i.d. and 30 cases of q.i.d.) was administered for an average of 7 days. The 160 cases included 34 cases of pharyngitis, 5 cases of tonsillitis, 8 cases of acute bronchitis, 8 cases of pneumonia, 52 cases of scarlet fever, 4 cases of acute purulent otitis media, 47 cases of urinary tract infection, 1 case of purulent lymphadenitis and 1 case of posthitis. Adverse reactions and abnormal clinical laboratory test results were also examined in 166 cases, including 6 cases excluded from the evaluation of clinical efficacy. The results obtained are summarized as follows: 1. With regard to GPC, MICs of CFPZ against 2 strains of S. aureus were 0.78 or 1.56 micrograms/ml and CFPZ showed the second highest activity to MCIPC. MICs of CFPZ against 49 strains of S. pyogenes were all less than 0.025 micrograms/ml.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗
PubMed1992

Characterization, self-assembly and reattachment of S layer from Clostridium botulinum type E saroma.

S layer of Clostridium botulinum type E Saroma and its subunits were isolated and characterized for their chemical and morphological properties. The S layer was composed of a number of subunits with apparent molecular weights ranging from about 10 to 150 kDa. The isolated S layer subunits possess the ability to assemble into recrystallized flat sheets in the absence of any supporting layer and to reattach to the cell wall from which they have been removed. Immunoblot analysis using an antiserum against whole cells of the organism showed that 60 kDa and 90 kDa subunits of the S layer were major somatic antigens of the organism. Immunogold-labeling using monospecific antiserum raised to the individual 60 and 90 kDa proteins revealed that both subunits were exposed evenly over the entire cell surface. The amino acid compositions of both subunits showed that aspartate and glutamate were predominant whereas cystine and methionine were poor. The amino acid composition and acidic property of the two subunits of the S layer agree well with the results obtained from the S layers of other bacterial species as well as other pathogenic clostridia.

Amino Acid Sequence↗
PubMed1992

In vitro self-assembly of the S layer subunits from Clostridium difficile GAI 0714 into tetragonal arrays.

Regularly arrayed surface component (S layer) of Clostridium difficile strain GAI 0714 was isolated with 4 M guanidine hydrochloride from the cell wall of the organism, and examined for self-assembly in vitro. The S layer was composed of two different protein subunits with molecular weights of 32 kDa and 45 kDa. Optical diffraction analysis revealed that the morphological units of both native and self-assembled S layer were essentially identical and composed of a rhombus possessing each side of 8.1 nm and interior angle of 88 degrees. The self-assembly of S layer subunits were induced in the presence of divalent cations such as Ca2+ or Zn2+, but Ba2+ or monovalent cations including K+, Na+ and Li+ failed to induce self-assembly. These results suggest that Ca+2 or Zn+2 may act as bridges to link negatively charged surface subunits.

Bacterial Outer Membrane Proteins↗
PubMed1992

Epitope specific antibody response against human type II collagen induced by anti-idiotypic antibody.

A species specific epitope on human type II collagen (CII) recognized with mAb, 2-60, was found to be localized on a cyanogen bromide-cleaved peptide (CB10) of human CII. To characterize the antibody response to the 2-60 epitope, we raised rabbit anti-idiotypic (Id) antibody against 2-60. The rabbit anti-2-60 Id antibody reacted not only with 2-60 mAb but also with 2-56 and 3-11 mAbs which were reactive with the epitopes related to the 2-60 epitope on CB10. The anti-Id antibody inhibited the binding of these three mAbs to human CII. Thus, rabbit anti-2-60 Id antibody recognized the cross-reactive idiotype expressed on 2-60, 2-56 and 3-11. The anti-2-60 Id antibody inhibited about thirty percent of the binding of polyclonal anti-human CII antibody derived from DBA/1J mice, thereby suggesting that the 2-60 idiotype might be expressed on a major fraction of the anti-human CII antibody. Immunization with the rabbit anti-2-60 Id antibody elicited antibody response to the 2-60 epitope, in DBA/1J (H-2q, Ighc), BALB/c (H-2d, Igha) and DBA/2 (H-2d, Ighc) mice. On the other hand, an epitope-specific antibody response induced by rabbit anti-Id antibody to 1-5 mAb reactive with a putative arthritogenic epitope on human CII was shown to be influenced by a single dominant gene, possibly the Igh gene. Our findings suggest that antibody responses against two distinct epitopes on human CII are probably regulated by different mechanisms.

Animals↗
PubMed1992

[Basic and clinical study of meropenem in pediatric field].

Meropenem (MEPM), a novel parenteral carbapenem antibiotic, was examined in a cooperative study involving 12 pediatric and 1 neonatologic facilities. The results are summarized as follows. 1. Antibacterial activity Antibacterial activity of MEPM against stock organisms including 31 strains of Streptococcus agalactiae, 14 of Listeria monocytogenes, 4 of Bordetella pertussis and 3 of Neisseria meningitidis ranged from 0.025 to 0.10 micrograms/ml in MIC90's, which were equal or lower than those of control drugs such as imipenem cefazolin, cefotiam, cefotaxime, ceftazidime and latamoxef. MICs against clinical isolates were as follows: In Gram-positive bacteria, MICs were 0.20 micrograms/ml to 6.25 micrograms/ml against 3 strains of Staphylococcus aureus, and 0.025 micrograms/ml or less against 4 of Streptococcus pneumoniae. In Gram-negative bacilli, MICs were 0.10 micrograms/ml to 0.20 micrograms/ml against 3 strains of Haemophilus influenzae and 0.78, 0.10 and 0.78 micrograms/ml, respectively, against one strain each of Enterobacter cloacae, Morganella morganii and Pseudomonas aeruginosa. MIC against 1 strain of Peptococcus saccharolyticus was < or = 0.025 micrograms/ml. 2. Pharmacokinetics Maximum plasma concentrations after intravenous infusion of MEPM over 30 minutes at doses of 10, 20 and 40 mg/kg, respectively, to 3 different groups of 3 children (total 9 cases) were observed at the completion of the treatment. Mean maximum concentrations in the 3 groups were 36.3, 69.5 and 129.8 micrograms/ml, respectively, exhibiting clear dose response. Mean plasma half lives in beta phase were 0.94, 0.86 and 0.94 hours, respectively, exhibiting no difference by doses, and this trend was observed also by HPLC. Urinary excretion rates in the first 6 hours after dose in the 10, 20 and 40 mg/kg groups were 67.3, 65.6 and 68.4%, respectively. Concentrations of MEPM in cerebrospinal fluid were determined in 2 cases of pyogenic meningitis. In 1 case, 500 mg (5.9 mg/kg) of MEPM was infused intravenously over 30 minutes and concentrations on Days 6, 8 and 15 observed at 190, 60 and 100 minutes after respective doses were 0.13, 0.10 micrograms/ml and less than the detection limit. Cerebrospinal fluid-plasma concentration ratio was determinable only on Day 8 and was 2.8%. In another case to which 250 mg (38.5 mg/kg) of MEPM was infused intravenously over 30 minutes, the concentration at Days 6, 7 and 10, 1 hour after the dose were less than the detection limit on day 6, and 2.04 and 2.62 micrograms/ml, respectively on days 7 and 10. 3. Clinical efficacy Clinical efficacies were evaluated in 49 cases and the efficacy rate was 93.9%.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1992

Difference in the functional maturation of T cells against Listeria monocytogenes in lymph nodes and spleen.

After subcutaneous immunization of mice with viable Listeria monocytogenes (LM), we evaluated the function of T cells induced in draining lymph nodes (LN) and spleen as determined by the local transfer of delayed-type hypersensitivity (DTH), acquired cellular resistance (ACR) and in vitro lymphokine production. LN cells could transfer specifically DTH but not ACR. In contrast, spleen cells from the same donor mice evoked the DTH response as well as bacterial clearance at the reaction site. Comparison of bacterial counts in spleen and in LN upon subcutaneous inoculation of mice with LM suggested that the lack of bacterial proliferation in LN underlay the failure to induce protective T cells in this lymphoid tissue. Spleen and LN T cells expressed CD4 and CD8 surface antigens equally and DTH response was solely dependent on CD4+ cells. Another major difference between LN and spleen cells was the profile of lymphokines produced in vitro. Upon the in vitro restimulation with killed Listeria, immune spleen cells produced macrophage chemotactic factor (MCF), interleukin-2 (IL-2) and interferon-gamma (IFN-gamma). In contrast, LN cells could produce all of the measured lymphokines but not IFN-gamma. The results provided strong evidence for the dissociation of DTH and ACR. Listerial growth appeared to be the requirement for full maturation of anti-listerial immunity that may coincide with the generation of IFN-gamma-producing T cells.

Animals↗
PubMed1992

A comparative study of once-a-day morning and once-a-day bedtime administration of 40 mg famotidine in treating gastric ulcers.

A randomized controlled study comparing once-a-day morning and once-a-day bedtime administration of 40 mg famotidine in treating gastric ulcers was carried out in 179 Japanese patients. Endoscopic examinations were performed at the baseline and repeated at 4-wk intervals until healing was confirmed. One hundred and sixty-four patients fulfilled the evaluation criteria (81 in the morning group and 83 in the bedtime group). The healing rates were 50.7% after 4 wk and 88.9% after 8 wk in the morning group and 46.5% after 4 wk and 74.7% after 8 wk in the bedtime group. The difference was statistically significant after 8 wk. Significant reductions from baseline for overall pain, beginning during the first 3 days, were likewise found in the two treatment groups. However, the pain severity in hunger state 1 wk after treatment was significantly higher in the bedtime group than in the morning group. Thus, once-a-day morning administration of 40 mg famotidine seems to be superior to once-a-day bedtime administration of 40 mg famotidine in treating gastric ulcers.

Adult↗
PubMed1991

Synthetic inositol 1,3,4,5-tetrakisphosphate analogs and their effect on the binding to microsomal fraction of rat cerebellum.

Binding activity of [3H]inositol 1,3,4,5-tetrakisphosphate (InsP4) was characterized with rat cerebellar membranes. Two types of InsP4 analog with either the aminobenzoyl or the aminocyclohexanecarbonyl group on the 2nd position of InsP4 have been synthesized and their effects on the binding activity were also examined. [3H]InsP4 binding was gradually displaced by increasing amounts of unlabeled InsP4, with an IC50 of 60-170 nM, depending on the pH values. The binding was sharply increased at acidic pH and millimolar concentrations of Ca2+, this being in clear contrast with [3H]InsP3 binding noted in the same species of tissue. Heparin inhibited the binding, with an IC50 of 1.7, 3 or 20 micrograms/ml at pH 8.3, 7.2 or 5.0, respectively. Adenine nucleotide inhibited the binding more potently than did [3H]InsP3 binding. InsP4 analogs were as effective as InsP4 in displacing [3H]InsP4 from rat cerebellar membranes, thereby indicating that the 2nd hydroxyl group may not be involved in recognition of InsP4 by its binding sites.

Animals↗
PubMed1991

Evidence for the involvement of endogenous thymidine in the density-inhibition of tumorigenic Chinese hamster V79 cells.

Two distinct low-molecular-weight growth inhibitory activities were isolated from supernatants of a density-inhibited, tumorigenic V79 Chinese hamster cell line. By chromatographic analyses, one of these was purified to homogeneity and eventually proved to be thymidine (dThd). In order to investigate the biological role of dThd in a density-inhibited culture of these cells, a dThd-kinase deficient (TK-) clone resistant to the excess of dThd was isolated from V79 cells and the effect of the supernatants on growth of these TK- or TK-proficient (TK+) cells was examined. As a result, the growth of TK- cells was not inhibited but enhanced by the supernatant at the concentrations which significantly inhibited the growth of TK+ cells. Such TK-dependent differential responses to supernatants suggest the presence of deoxyribonucleosides including a high level of dThd in the supernatants. Since it is unlikely that dThd might derive from denatured DNA of dead cells, an accumulation of endogenous dThd in confluent culture appears to be responsible for dThd triphosphates which are synthesized de novo, degraded and excreted into the medium rather than incorporated into DNA as a consequence of aberrant growth in the presence of certain growth inhibitors produced by density-inhibited V79 cells.

Animals↗
PubMed1991

6-Deoxy-D-talan and 6-deoxy-L-talan. Novel serotype-specific polysaccharide antigens from Actinobacillus actinomycetemcomitans.

Serotype-specific polysaccharide antigens from Actinobacillus actinomycetemcomitans ATCC 29523 (serotype a) and NCTC 9710 (serotype c) were extracted from whole cells by autoclaving and purified by ion-exchange chromatography and gel filtration. Analysis of component sugars by gas-liquid chromatography-mass spectrometry, high performance liquid chromatography, and NMR together with optical rotation data showed that the serotype a antigen was composed solely of 6-deoxy-D-talose, whereas the serotype c antigen consisted of 6-deoxy-L-talose. Structural analysis indicated that both of these antigens were composed of closely related repeating units, -3)-6-deoxy-alpha-D-Talp-(1-2)-6-deoxy-alpha-D-Talp-(1-(sero type a) and -3)-6-deoxy-alpha-L-Talp-(1-2)-6-deoxy-alpha-L-Talp-(1-(sero type c). 1H and 13C NMR analysis showed that both of these serotype antigens contained one acetyl group/2 sugar residues. These acetyl groups localized at the O-2 position of 3-linked 6-deoxy-D-talose (serotype a) or O-4 position of 3-linked 6-deoxy-L-talose residues (serotype c), respectively. These results coupled with our previous findings on the serotype b antigen (Amano, K., Nishihara, T., Shibuya, N., Noguchi, T., and Koga, T. (1989) Infect. Immun. 57, 2942-2946) showed that the serotype antigens from A. actinomycetemcomitans are a group of novel polysaccharides with structural features closely related biosynthetically.

Actinobacillus↗
PubMed1991

Evidence for coupling of bradykinin receptors to a guanine-nucleotide binding protein to stimulate arachidonate liberation in the osteoblast-like cell line, MC3T3-E1.

The effect of bradykinin on the activation production of inositol 1,4,5-trisphosphate and prostaglandin E2 (PGE2) was examined in the murine osteoblastic cell line, MC3T3-E1. Bradykinin, at concentrations ranging from 1 to 1000 nM, stimulated the production of inositol 1,4,5-trisphosphate 2.5- to 3-fold within 10 s, and elevated cytosolic-free Ca2+, even in the absence of external Ca2+. This process is mediated through the activation of phospholipase C. Bradykinin at the same concentration also stimulated the production of PGE2 and caused a release of 3H radioactivity from the cells prelabeled with [3H]arachidonic acid, probably via the activation of phospholipase A2. Pretreatment of the cells with pertussis toxin inhibited the stimulation of PGE2 production and 3H radioactivity release, while the elevation in cytosolic Ca2+ and the production of inositol 1,4,5-trisphosphate were not altered by toxin-pretreatment. The addition of an unhydrolyzable analog of GTP, guanosine 5'-[gamma-thio]triphosphate (GTP gamma S) to the beta-escin-permeabilized cells prelabeled with [3H]arachidonic acid enhanced the release of 3H radioactivity. The simultaneous presence of bradykinin with GTP gamma S further activated the 3H radioactivity release in the beta-escin-permeabilized cells. These results provide evidence that receptors for bradykinin in the MC3T3-E1 couple stimulating arachidonate release, probably via the activation of phospholipase A2, through a guanine nucleotide binding protein sensitive to pertussis toxin.

Animals↗
PubMed1991

Synthetic inositol 1,3,4,5-tetrakisphosphate analogues.

Inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4] analogues were synthesized and their effects on [3H]Ins(1,3,4,5)P4 5-phosphatase, [3H]Ins(1,3,4,5)P4 3-phosphatase and [3H]inositol 1,4,5-trisphosphate [3H]Ins(1,4,5)P3] 5-phosphatase activities were examined. The Ins(1,3,4,5)P4 analogue with the aminobenzoyl group at the 2-position of Ins(1,3,4,5)P4 inhibited the hydrolysis of 5-phosphate of [3H]Ins(1,3,4,5)P4 catalysed by erythrocyte ghosts, with a lower Ki value than seen with Ins(1,3,4,5)P4, whereas the analogue with the aminocyclohexanecarbonyl group at the same position had a higher Ki value. The Ins(1,4,5)P3 analogues that we had previously synthesized were also capable of inhibiting this process, with the same tendency as Ins(1,3,4,5)P4 analogues. Such differences in the potency among Ins(1,3,4,5)P4 and Ins(1,4,5)P3 analogues were applicable to other phosphatase activities, namely [3H]Ins(1,3,4,5)P4 3-phosphatase and [3H]Ins(1,4,5)P3 5-phosphatase. These results suggest that the active sites of these enzymes may catalyse the dephosphorylation in a similar fashion.

Erythrocyte Membrane↗
PubMed1991

Immunogenicity and protective effect against oral colonization by Streptococcus mutans of synthetic peptides of a streptococcal surface protein antigen.

Streptococcus mutans is known to be a major causative organism of human dental caries. A surface protein Ag with a molecular mass of 190 kDa of S. mutans (PAc) is receiving attention as an anticaries vaccine. We have recently determined the complete nucleotide sequence of the gene for PAc. In this study, four peptides were synthesized on the basis of amino acid sequence of PAc. Among these peptides, PAc(301-319) corresponding to the alanine-rich repeating amino acid region was the most strongly bound by polyclonal murine anti-rPAc antibodies. The peptide partially inhibited the binding of polyclonal anti-rPAc antibodies to rPAc. The peptide induced the proliferation of T cells from BALB/c mice immunized with rPAc. Subcutaneous immunization with PAc(301-319) or rPAc emulsified in CFA/IFA induced high serum IgG responses to rPAc and PAc(301-319). In addition, serum IgG responses to a surface protein Ag with a molecular mass of 210 kDa of Streptococcus sobrinus were elicited in mice immunized by s.c. injection with PAc(301-319) or rPAc. Intranasal immunization with PAc(301-319) coupled to cholera toxin B subunit (CTB) or with rPAc and free CTB induced high serum IgG responses to rPAc. The immunization with PAc(301-319) coupled to CTB or rPAc and free CTB suppressed the colonization of murine teeth by S. mutans. These results suggest that intranasal immunization with the peptide or rPAc may be effective for the prevention of dental caries.

Animals↗