Membrane localization of protein-tyrosine phosphatase 1B is essential for its activation of sterol regulatory element-binding protein-1 gene expression.

Sterol regulatory element-binding protein-1 (SREBP-1) is a key transcription factor in stimulating lipogenesis in the liver. Protein-tyrosine phosphatase 1B (PTP1B) induces SREBP-1 gene expression via protein phosphatase 2A (PP2A) activation. PTP1B is reported to be anchored on the endoplasmic reticulum (ER) via its C-terminal tail, and change in intracellular localization of PTP1B by C-terminal-truncation did not alter its inhibitory effects on insulin signaling. In this study, we investigated whether the change in intracellular localization of PTP1B could influence SREBP-1 gene expression. Overexpression of C-terminal truncated PTP1B (PTP1BdeltaCT) in rat Fao cells did not induce SREBP-1 gene expression. Furthermore, PTP1BdeltaCT failed to bind PP2A, resulting in impaired PP2A activation, whereas overexpression of wild-type PTP1B (PTP1BWT) associated with PP2A. Moreover, a membrane-targeted PTP1BDeltaCT activated PP2A with restored PP2A binding, despite the absence of its C-terminal region. Finally, overexpression of PTP1BdeltaCT into mouse primary cultured hepatocytes failed to enhance SREBP-1c mRNA, whereas membrane-targeted PTP1BdeltaCT led to enhanced SREBP-1c mRNA in hepatocytes as well as PTP1BWT. In conclusion, membrane localization of PTP1B is essential for PP2A activation, which is crucial for its enhancement of SREBP-1 gene expression.

Increased expression of CCAAT/enhancer binding protein-beta and -delta and monocyte chemoattractant protein-1 genes in aortas from hyperinsulinaemic rats.

AIMS/HYPOTHESIS: We evaluated whether hyperinsulinaemia stimulates the expression of transcription factor CCAAT/enhancer binding protein (C/EBP)-beta and C/EBP-delta and leads to the induction of the chemokine (C-C motif) ligand 2 gene (Ccl2, also known as MCP-1) expression in aortas. METHODS: Hyperinsulinaemia was induced by feeding rats a high-fructose diet. CCL2 production was analysed by ELISA. The expression of Ccl2, Cebpb and Cebpd mRNAs was investigated by quantitative RT-PCR. The binding of C/EBP-beta to Ccl2 was assessed by chromatin immunoprecipitation (ChIP) assay. RESULTS: Insulin at a concentration of 10 nmol/l significantly stimulated the expression of Cebpb, Cebpd and Ccl2 mRNAs, depending on activation of phosphatidylinositol 3-kinase (PI3K) in cultured vascular smooth muscle cells. The knock-down of C/EBP-beta with siRNA abolished the insulin-induced Ccl2 mRNA expression. In the aortas from fructose-fed rats, the levels of phosphorylation of Akt/protein kinase B, a downstream effector of PI3K, were also increased. The expression of Cebpb, Cebpd and Ccl2 mRNAs in the aortas from fructose-fed rats were significantly elevated, by 330, 300 and 300%, respectively, compared with those of control-fed rats. The induction Ccl2 mRNA expression in the aortas was significantly correlated with the expression of Cebpb and Cebpd mRNAs in the aortas. Furthermore, the ChIP assay showed elevated binding of C/EBP-beta to the 5' upstream region of Ccl2 in the aortas from fructose-fed rats. CONCLUSIONS/INTERPRETATION: These findings clearly indicate the role of C/EBPs in the mechanism of upregulation of CCL2, an inflammation-related protein, observed in the hyperinsulinaemic state, which may initiate the process of atherosclerosis.

Mode of perturbation of Asahi fibrin assembly by the extra oligosaccharides.

Steric hindrance by the backbone of extra oligosaccharides at gamma-Asn 308 may cause the repulsive force to widen the junction at the D:D interface, and thus, interfere with the longitudinal elongation and lateral association of protofibrils.

[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (1998)].

The bacteria isolated from the patients with lower respiratory tract infections were collected by institutions located throughout Japan, since 1981. Ikemoto et al. have been investigating susceptibilities of these isolates to various antibacterial agents and antibiotics, and analyzed some characteristics of the patients and isolates from them each year. Results obtained from these investigations are discussed. In these 18 institutions around the entire Japan, 532 strains of presumably etiological bacteria were isolated mainly from the sputa of 438 patients with lower respiratory tract infections during the period from October in 1998 to September in 1999. MICs of various antibacterial agents and antibiotics were determined against 85 strains of Staphylococcus aureus, 100 strains of Streptococcus pneumoniae, 96 strains of Haemophilus influenzae, 75 strains of Pseudomonas aeruginosa (non-mucoid strains), 6 strains of Pseudomonas aeruginosa (mucoid strains), 38 strains of Moraxella subgenus Branhamella catarrhalis, 26 strains of Klebsiella pneumoniae etc., and the susceptibilities of 517 strains were assessed except for those strains that died during transportation. S. aureus strains for which MICs of oxacillin (MPIPC) were higher than 4 micrograms/ml (methicillin-resistant S. aureus: MRSA) accounted for 60.0%. Vancomycin (VCM) and arbekacin (ABK) showed the most potent activities against MRSA. But one of MRSA showed resistance to ABK with the MIC of 64 micrograms/ml. The sensitive strains of MRSA to VCM have decreased. The frequency of penicillin (PC)-intermediate S. pneumoniae (PISP) + PC-resistant S. pneumoniae (PRSP) have increased in 46.0% for 1998 comparatively from 30.9% of 1997's. But PRSP decreased, and PISP increased into 39.0% of 1998 years from 19.8% of 1997's. Panipenem (PAPM), imipenem (IPM) and faropenem (FRPM) showed the most potent activities against S. pneumoniae with MIC80s of 0.125 microgram/ml or below. Against H. influenzae and M. (B.) catarrhalis, almost all the drugs showed good activities. The sensitive strains of them against ceftazidime (CAZ) decreased in 1997, but those have increased in 1998. Inversely, the susceptibility of them against cefotiam (CTM) had been higher in 1997, but those have been lower in 1998. Tobramycin (TOB) showed the most potent activity against P. aeruginosa (both mucoid and nonmucoid strains). All drugs except ampicillin (ABPC) were active against K. pneumoniae. A quite few of K. pneumoniae showed low susceptibilities. Also, we investigated year to year changes in the characteristics of patients, their respiratory infectious diseases, and the etiology. The examination of age distribution indicated that the proportion of patients with ages over 70 years was 48.6% of all the patients showing a slight increase in every year. About the proportion of diagnosed diseases as follows: Bacterial pneumonia was the most frequent with 40.2%. The ratio of it has increased slightly, and the increased rate was 10% in patients with ages over 70 years compared with the results in 1997. Chronic bronchitis have decreased slightly with 27.6% in 1998. Number of strains isolated from patients before administration of antibiotics were more than those after administration of them in chronic bronchitis, but these were almost same number in bacterial pneumonia. Administration of antibiotics has changed the results of the frequency of isolation of bacterial species. Bacterial isolations before administration of antibiotics were as follows: S. pneumoniae 26.7%, H. influenzae 23.8%, S. aureus 13.3% and M. (B.) catarrhalis 10.8%. The frequencies of S. aureus decreased after antibiotics administration over 15 days, but the frequencies of P. aeruginosa (both mucoid and non-mucoid) was not affected. The frequencies of P. aeruginosa was 45.5% after administration over 15 days. The frequencies of S. pneumoniae decreased upon administration of antibiotics, these were only 4.5% over 15 days. The frequencies of H. (

[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (1997)].

The bacteria isolated from the patients with lower respiratory tract infections were collected by institutions located throughout Japan, since 1981. Ikemoto et al. have been investigating susceptibilities of these isolates to various antibacterial agents and antibiotics, and analyzed some characteristics of the patients and isolates from them each year. Results obtained from these investigations are discussed. In these 17 institutions around the entire Japan, 512 strains of presumably etiological bacteria were isolated mainly from the sputa of 440 patients with lower respiratory tract infections during the period from October in 1997 to September in 1998. MICs of various antibacterial agents and antibiotics were determined against 100 strains of Staphylococcus aureus, 81 strains of Streptococcus pneumoniae, 85 strains of Haemophilus influenzae. 71 strains of Pseudomonas aeruginosa (non-mucoid strains), 27 strains of Pseudomonas aeruginosa (mucoid strains), 33 strains of Moraxella subgenus Branhamella catarrhalis, 17 strains of Klebsiella pneumoniae etc., and the susceptibilities of these strains were assessed except for those strains that died during transportation. S. aureus strains for which MICs of oxacillin (MPIPC) were higher than 4 micrograms/ml (methicillin-resistant S. aureus: MRSA) accounted for 55.0%. The frequency of the drug resistant bacteria decreased comparing to the previous year's 67.3%. Arbekacin (ABK) and vancomycin (VCM) showed the most potent activities against MRSA. Imipenem (IPM) and panipenem (PAPM) of carbapenems showed the most potent activities with MIC80S of 0.063 microgram/ml against S. pneumoniae. The frequency of penicillin (PC)-intermediate S. pneumoniae (PISP)+PC-resistant S. pneumoniae (PRSP) had decreased gradually, that is, in 1995 the frequency of it was 40.3%, but that was 30.9% in 1997. Against H. influenzae and M.(B.) catarrhalis, all the drugs showed good activities. But the sensitive strains of them against ceftazidime (CAZ) had decreased in 1997, compared those in 1995 and 1996. Meropenem (MEPM), IPM and tobramycin (TOB) showed the most potent activity against P. aeruginosa (mucoid strains). And TOB and ciprofloxacin (CPFX) showed the most potent activities against P. aeruginosa (non-mucoid strains). All drugs except ampicillin (ABPC) were more active against K. pneumoniae in 1997 than that in 1996. Also, we investigated year to year changes in the characteristics of patients, their respiratory infectious diseases, and the etiology. The examination of age distribution indicated that the proportion of patients with ages over 70 years was 45.5% of all the patients showing a slight increase year by year. About the proportion of diagnosed diseases, not so particular changes were recognized as follows: Bacterial pneumonia and chronic bronchitis were the most frequent with 33.6% and 29.1%, respectively. Number of strains isolated from patients before administration of antibiotics were more than those after administration of them in chronic bronchitis, but these had reversed in bacterial pneumonia. The tendency in bacterial pneumonia had been acknowledged since 1995. The increase of S. aureus and P. aeruginosa (both mucoid and non-mucoid strains) isolated after administration of antibiotics, has suggested the decrease of the susceptibility of these strains against antibiotics. Administration of antibiotics has changed the results of the frequency of isolation of bacterial species. Bacterial isolations before administration of antibiotics were as follows: S. pneumoniae 24.5%, H. influenzae 21.4%, S. aureus 18.4% and P. aeruginosa 12.2%. The frequencies of S. aureus decreased after antibiotics administration over 15 days, but the frequencies of P. aeruginosa was not affected. The frequencies of P. aeruginosa was 47.8% after administration over 15 days. From patients administered antibiotics of penicillins and cephems. S. aureus was mainly detected with 31.7-58.3%, and from patients administere

[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (1996)].

The bacteria isolated from the patients with lower respiratory tract infections were collected by institutions located throughout Japan, since 1981. Ikemoto et al. have been investigating susceptibilities of these isolates to various antibacterial agents and antibiotics, and characteristics of the patients and isolates from them each year. Results obtained from these investigations are discussed. In 16 institutions around the entire Japan, 557 strains of presumably etiological bacteria were isolated mainly from the sputa of 449 patients with lower respiratory tract infections during the period from October 1996 to September 1997. MICs of various antibacterial agents and antibiotics were determined against 98 strains of Staphylococcus aureus, 93 strains of Streptococcus pneumoniae, 84 strains of Haemophilus influenzae, 84 strains of Pseudomonas aeruginosa (non-mucoid strains), 17 strains of Pseudomonas aeruginosa (mucoid strains), 31 strains of Moraxella subgenus Branhamella catarrhalis, 21 strains of Klebsiella pneumoniae etc., and the drug susceptibilities of these strains were assessed except for those strains that died during transportation. 1) S. aureus S. aureus strains for which MICs of oxacillin (MPIPC) were higher than 4 micrograms/ml (methicillin-resistant S. aureus) accounted for 67.3%. The frequency of the drug resistant bacteria increased comparing to the previous year's 52.7%. Arbekacin (ABK) and vancomycin (VCM) showed the highest activities against both S. aureus and MRSA with MIC80s of 1 microgram/ml. 2) S. pneumoniae Imipenem (IPM) and panipenem (PAPM) of carbapenems showed the most potent activities with MIC80s of 0.063 microgram/ml. Faropenem (FRPM) showed the next potent activity with MIC80 of 0.125 microgram/ml. The other drugs except erythromycin (EM), clindamycin (CLDM) and tetracycline (TC) were active against S. pneumoniae tested with MIC80s of 8 micrograms/ml or below. 3) H. influenzae The activities of all drugs were potent against H. influenzae tested with MIC80s of 4 micrograms/ml or below. Cefotiam (CTM), cefmenoxime (CMX), cefditoren (CDTR) and ofloxacin (OFLX) showed the most potent activities with MIC80s of 0.063 microgram/ml. 4) P. aeruginosa (mucoid strains) Tobramycin (TOB) showed the most potent activity against P. aeruginosa (mucoid strains) with MIC80 of 1 microgram/ml. Ceftazidime (CAZ), cefsulodin (CFS), IPM, gentamicin (GM), ABK and ciprofloxacin (CPFX) showed the next potent activities, with MIC80s of 2 micrograms/ml. The MIC80s of the other drugs ranged from 4 micrograms/ml to 16 micrograms/ml. 5) P. aeruginosa (non-mucoid strains) TOB and CPFX showed the most potent activities against P. aeruginosa (non-mucoid strains) with MIC80s of 1 microgram/ml. The MIC80s of piperacillin (PIPC) and cefoperazone (CPZ) were 16 micrograms/ml in 1995, and they were 64 micrograms/ml in 1996. 6) K. pneumoniae All drugs except ampicillin (ABPC) were active against K. pneumoniae. CMX, cefpirome (CPR), cefozopran (CZOP) and carumonam (CRMN) showed the most potent activities against K. pneumoniae with MIC80s of 0.125 microgram/ml. The MIC80s of the other drugs ranged from 0.25 microgram/ml to 2 micrograms/ml. 7) M.(B) catarrhalis Against M.(B.) catarrhalis, all drugs showed good activities with MICs of 4 micrograms/ml or below. IPM and minocycline (MINO) showed the most potent activities with MICs of 0.063 microgram/ml. Also, we investigated year to year changes in the characteristics of patients, their respiratory infectious diseases, and the etiology. Patients' backgrounds were examined for 557 isolates from 449 cases. The examination of age distribution indicated that the proportion of patients with ages over 60 years was 71.0% of all the patients showing a slight increase over that in 1994. Proportions of diagnosed diseases were as follows: Bacterial pneumonia and chronic bronchitis were the most frequent with 35.9% and 30.3% respectively. They were followed by bronchiectasis with a proportion of 10.

[Usefulness of 7 day therapy with cefluprenam in the management of respiratory tract infections].

Efficacy and safety of a newer injectable cephalosporin, cefluprenam (CFLP) on cases with bacterial pneumonia and chronic respiratory tract infections were evaluated at a dose of 1g (potency), d.i.d for 7 days. 1. Of 130 cases in total, 116 cases were enrolled for the clinical efficacy evaluation. The efficacy rate (excellent and good responses) was 94.8% (110/116). The efficacy rate was 93.8% (60/64) for cases with bacterial pneumonia, and 96.2% (50/52) for cases with chronic respiratory tract infections. The recurrence was noted in 1.2% (1/82). The bacteriological response rate was 100.0% (32/32) for gram positive cocci, 93.8% (15/16) for gram negative rods and 97.9% (47/48) in total. 2. Adverse drug reactions were noted in 3.9% (5/129), consisting of 2 cases with skin rash, 1 case with drug fever, 1 case with skin rash and skin itching and 1 case with drug fever and headache. The abnormal laboratory changes were noted in 23.6% (30/127), mainly containing the elevation in GPT and GOT, and eosinophylia. The safety rate (no problem evaluation) was 74.8% (95/127). 3. The usefulness rate (very useful and useful evaluations) was 93.1% (108/116). As suggested by the evaluation on the secondary endpoint in the phase III comparative studies with both bacterial pneumonia and chronic respiratory tract infections, it was confirmed that the 7 day therapy of CFLP was promising for treatment of moderate bacterial pneumonia and chronic respiratory tract infections, because the high clinical efficacy was obtained and also the incidence of allergic reactions with CFLP was almost the same as that of ceftazidime (CAZ) evaluated highly safe. Based on these results, it was concluded that CFLP was useful in the management of moderate respiratory tract infections and also the recommended therapeutic period with CFLP was within 7 days.

[Susceptibilities of bacteria isolated from patients with respiratory infectious diseases to antibiotics (1994)].

Bacteria isolated from lower respiratory tract infections were collected in cooperation with institutions located throughout Japan, since 1981. IKEMOTO et al. have been investigating susceptibilities of these isolates to various antibacterial agents and antibiotics, and characteristics of the patients and isolates from them each year. Results obtained from these investigations are discussed. In 23 institutions around the entire Japan, 492 strains of presumably etiological bacteria were isolated mainly from the sputum of 421 patients with lower respiratory tract infections from October 1994 to September 1995. MICs of various antibacterial agents and antibiotics were determined against 70 strains of Staphylococcus aureus, 101 strains of Streptococcus pneumoniae, 92 strains of Haemophilus influenzae, 61 strains of Pseudomonas aeruginosa (non-mucoid strains), 25 strains of Pseudomonas aeruginosa (mucoid strains), 48 strains of Moraxella subgenus Branhamella catarrhalis, 14 strains of Klebsiella pneumoniae etc., and the drug susceptibilities of these strains were assessed except for those strains that died during transportation. 1. S. aureus. S. aureus strains for which MICs of oxacillin were higher than 4 micrograms/ml (methicillin-resistant S. aureus) accounted for 51.4%, but the frequency of the drug resistant bacteria decreased comparing to the previous year's 56.0%. Vancomycin showed the highest activity against S. aureus with MIC80 of 0.5 microgram/ml. 2. S. pneumoniae. Most of the drugs tested showed potent activities against S. pneumoniae. Imipenem of carbapenems showed the most potent activity with MIC80 was 0.063 microgram/ml. Erythromycin and clindamycin showed low activities with MIC80s > or = 256 micrograms/ml. Among these strains, however, 46.5% and 68.3% of strains, were quite sensitive toward these agents, respectively, with MICs of 0.063 microgram/ml. 3. H. influenzae. The activities of all drugs were potent against H. influenzae tested. Cefmenoxime a cephem, showed the most potent activity, the MICs of this drug against all of the 92 strains were 0.063 microgram/ml. Ofloxacin also showed a potent activity, and inhibited about 96% of strains with MIC of 0.063 microgram/ml. 4. P. aeruginosa (mucoid strains). Tobramycin showed the most potent activity against P. aeruginosa (mucoid strains) with MIC80 of 0.5 microgram/ml. Gentamicin, arbekacin and ciprofloxacin showed next potent activities, and their MIC80s were 2 micrograms/ml. 5. P. aeruginosa (non-mucoid strains). Tobramycin showed the most potent activity against P. aeruginosa (non-mucoid strains) with MIC80 of 2 micrograms/ml. Comparing to the activities against P. aeruginosa (mucoid strains), the activities of all the drugs tested were lower against P. aeruginosa (non-mucoid strains). 6. K. pneumoniae. Carumonam showed the most potent activity against K. pneumoniae with MIC80 of 0.063 microgram/ml. Cefozopran showed the next most potent activity with MIC80 of 0.125 microgram/ml. Ampicillin and cephems except cefpodoxime, cefozopran and cefditoren showed low activities and their MIC80s were > or = 16 micrograms/ml, and their MICs were all higher than > or = 4 micrograms/ml. 7. M. (B.) catarrhalis. Imipenem and ofloxacin showed the most potent activities against M. (B.) catarrhalis, their MIC80s were 0.063 microgram/ml. Erythromycin and minocycline showed the next highest activities with their MIC80s at 0.25 microgram/ml. Also, we investigated year to year changes in the background of patients, the respiratory infectious diseases, and the etiology of bacteria. Patients characteristics, in this period of investigation showed varieties of infectious diseases found in patients in a high age bracket, and the patients over age 60 accounted for 62.0% of all the cases. Different lower respiratory tract infectious were distributed as follows: chronic bronchitis and bacterial pneumonia accounted for the greatest number of cases with 35.6%, 27.1%, respectively, followed by

[Susceptibilities of bacteria isolated from patients with respiratory infectious diseases to antibiotics (1993)].

Bacteria isolated from respiratory tract infections were collected in cooperation with institutions located throughout Japan, since 1981, and the Ikemotor et al. have been investigating susceptibilities of the isolates of various antibacterial agents and antibiotics, and the relationships between the isolates and backgrounds of the patients and so forth each year. We discuss the results in detail. In 20 institutions around the entire Japan from October 1993 to September 1994, 584 strains of bacteria were isolated mainly from sputa of 473 patients with respiratory tract infections and presumed to be the etiological agents. MICs of various antibacterial agents and antibiotics were determined against 91 strains of Staphylococcus aureus, 98 strains of Streptococcus pneumoniae, 122 strains of Haemophilus influenzae, 91 strains of Pseudomonas aeruginosa (non-mucoid), 34 strains of Pseudomonas aeruginosa (mucoid), 42 strains of Moraxella subgenus Branhamella catarrhalis, 25 strains of Klebsiella pneumoniae etc., and the drug susceptibilities of these strains were measured except the strains which died during transportation. 1. S. aureus S. aureus strain sfor which MICs of methicillin was higher than 4 micrograms/ml (methicillin-resistant S. aureus) accounted for 56.0%, but this frequency of the drug resistant bacteria was lower than the previous year's 61.4%. Arbekacin and vancomycin showed the highest activities against MRSA and MIC80s were 1 microgram/ml. 2. S. pneumoniae Benzylpenicillin among the penicillins showed potent activities against S. pneumoniae. Cefuzonam, cefotaxime and cefmenoxime among the cephems showed excellent antimicrobial activities against S. pneumoniae. Imipenem; carbapenems, showed the most potent activity, and MIC90 was 0.063 microgram/ml. 3. H. influenzae All the drugs tested were quite active against H. influenzae. Cefotaxime, cefmenoxime, cefuzonam and cefixime among the cephems showed the most potent activities, and MIC90 were 0.063 microgram/ml against H. influenzae. Ofloxacin also showed MIC90 of 0.063 microgram/ml. 4. P. aeruginosa (mucoid) Tobramycin showed the most potent activity against P. aeruginosa (mucoid), and MIC80 was 1 microgram/ml. Ceftazidime, cefsulodin, imipenem, aztreonam, gentamicin and ciprofloxacin showed potent activities with MIC80s of 2 micrograms/ml. 5. P. aeruginosa (non-mucoid) Tobramycin showed the highest activity against P. aeruginosa (non-mucoid), and MIC80 was 1 microgram/ml, followed by ciprofloxacin with MIC80 of 2 micrograms/ml. Comparing to activities against P. aeruginosa (mucoid), all the drugs tested had relatively low activities against P. aeruginosa (non-mucoid). 6. K. pneumoniae. The activities of all drugs except ampicillin and minocycline were high against K. pneumoniae. Cefozopran, imipenem and carumonam showed the highest activities and MIC80s were 0.125 microgram/ml. Flomoxef showed the next highest activities with an MIC80 of 0.25 microgram/ml. 7. M.(B.) catarrhalis Imipenem showed the most potent activity against M.(B.) catarrhalis, with an MIC80 of 0.063 microgram/ml, followed minocycline and ofloxacin with their MIC80s of 0.125 microgram/ml. We also investigated year to year changes in the background of patients, as well as types of respiratory infectious diseases, and the etiological agents. As for patients background, there were many infectious diseases found among patients a high age bracket, and the patients over age 60 accounted for 61.3% of the diseases. The distribution by respiratory tract infections was as follows: chronic bronchitis and bacterial pneumonia accounted for the greatest numbers of cases with 31.1% and 26.0%, respectively, followed by bronchiectasis with 10.4%. In this year chronic bronchitis under age 29 were 41.7%, thus was much higher than 12.5% in previous year. This marked change was first noted in your research during the recent 5 years. As for frequencies of etiologic bacteria by respiratory tract infections, S. pneumoniae (ABSTRACT TRUNCATED)

[Susceptibilities of bacteria isolated from patients with respiratory infectious diseases to antibiotics (1992)].

Bacteria isolated from lower respiratory tract infections were collected in cooperation with institutions located throughout Japan since 1981, and Ikemoto et al. have been investigating susceptibilities of the isolates to various antibacterial agents and antibiotics, and the relationships between the isolates and characteristics of the patients and so forth each year. We discuss the results in detail. In 20 institutions around the entire Japan from October 1992 to September 1993, 690 strains of bacteria were isolated mainly from sputa of 549 patients with lower respiratory tract infections and presumed to be the etiological bacteria. MICs of various antibacterial agents and antibiotics were determined against 101 strains of Staphylococcus aureus, 121 strains of Streptococcus pneumoniae, 122 strains of Haemophilus influenzae, 92 strains of Pseudomonas aeruginosa (non-mucoid), 32 strains of Pseudomonas aeruginosa (mucoid), 52 strains of Moraxella subgenus Branhamella catarrhalis, 28 strains of Klebsiella pneumoniae etc., and the drug susceptibilities of these strains were measured except the strains which died during transportation. 1. S. aureus S. aureus strains for which MICs of methicillin were higher than 4 micrograms/ml (methicillin-resistant S. aureus) accounted for 61.4% and the frequency of the drug resistant bacteria was higher than the previous year's 58.3%. MICs values indicated that arbekacin was as active as vancomycin against all the strains on S. aureus. 2. S. pneumoniae Benzylpenicillin among the penicillins showed potent activities against S. pneumoniae. Cefuzonam, cefazolin, cefotaxime and cefmenoxime among the cephems showed excellent antimicrobial activities against S. pneumoniae. Imipenem; carbapenems, showed the most potent activity, and MIC80 was 0.015 microgram/ml. 3. H. influenzae All the drugs tested were potent against H. influenzae. Ampicillin among the penicillins showed MIC80 1 microgram/ml against H. influenzae. Cefotaxime, cefmenoxime, cefuzonam and cefixime showed the most potent activities, and MIC80s were 0.063 microgram/ml. The antimicrobial activity of ofloxacin was equivalent to those of cephems. 4. P. aeruginosa (mucoid) Ciprofloxacin showed the most potent activity against P. aeruginosa (mucoid), and MIC80 was 1 microgram/ml. Cefsulodin, aztreonam, carumonam and tobramycin showed the next most potent activities with an MIC80s of 2 micrograms/ml. 5. P. aeruginosa (non-mucoid) Tobramycin and ciprofloxacin showed the highest activities against P. aeruginosa (non-mucoid) with an MIC80s of 2 micrograms/ml. Norfloxacin also showed some activity, and MIC80 was 4 micrograms/ml. Comparing to activities against P. aeruginosa (mucoid), all the drugs tested showed lower activities against P. aeruginosa (non-mucoid). 6. K. pneumoniae The activities of all drugs except penicillins were high activities against K. pneumoniae. Carumonam showed the most potent activity with an MIC80 of 0.063 microgram/ml, followed by flomoxef, cefixime and cefozopran with their MIC80s of 0.125 microgram/ml. 7. M.(B.) catarrhalis Imipenem; carbapenems, showed the most potent activity against M.(B.) catarrhalis with an MIC80 0.063 microgram/ml. Minocycline and ofloxacin showed MIC80s 0.125 microgram/ml, respectively. We also investigated year to year changes in the background of patients, as well as types of respiratory infectious diseases, and the etiological bacteria. As for patients backgrounds, there were many infectious diseases found among patients in a high age bracket, and the patients over age 60 accounted for 60.8% of the diseases. The distribution by lower respiratory tract infections was as follows: bacterial pneumonia and chronic bronchitis accounted for the greatest numbers of cases with 30.4%, 29.5%, respectively, followed by bronchiectasis with 12.2%. As for frequencies of etiologic bacteria for respiratory tract infections, H. influenzae: 22.2%, and S. pneumoniae: 15.1% in chronic bronchitis; S. pneumoniae: 2

[Pharmacokinetics of flomoxef in children undergoing chronic hemodialysis].

The pharmacokinetics of flomoxef (FMOX), an oxacephem antibiotic, were investigated in pediatric patients undergoing chronic hemodialysis. The results are summarized as follows. 1. FMOX was given intravenously in a single dose of 10 mg/kg to 5 pediatric patients (ranging from 7 to 15 years of age) undergoing chronic hemodialysis. It was also given in a dose of 5 mg/kg to 2 of these patients. Its concentrations in serum and urine were determined using bioassay. Pharmacokinetic analyses were performed using a two compartment open model. 2. The serum concentrations of FMOX, administered in doses of 10 mg/kg or 5 mg/kg on non-hemodialysis days, were 33.3 +/- 4.09 micrograms/ml (mean +/- standard deviation) and 17.6 micrograms/ml (mean) at 30 minutes after injection, 29.6 +/- 3.51 micrograms/ml and 15.9 micrograms/ml at 1 hour, 27.2 +/- 2.14 micrograms/ml and 15.1 micrograms/ml at 2 hours, 23.5 +/- 1.90 micrograms/ml and 13.0 micrograms/ml at 4 hours, 20.8 +/- 2.44 micrograms/ml and 12.2 micrograms/ml at 6 hours, 18.9 +/- 1.86 micrograms/ml and 11.0 micrograms/ml at 8 hours, and 9.64 +/- 1.43 micrograms/ml and 6.16 micrograms/ml at 24 hours, respectively. 3. The urinary concentrations of FMOX, administered in a dose of 10 mg/kg, were 42.4-123 micrograms/ml between 0-6 hours after injection, 14.1-52.5 micrograms/ml between 6-24 hours, and 2.86-23.7 micrograms/ml between 24-48 hours. The urinary excretion rate in the first 48 hours after injection ranged from 9.1 to 10.5%.(ABSTRACT TRUNCATED AT 250 WORDS)

[The effect of cefaclor on the nasopharyngeal pathogens in children].

Nasopharyngeal specimens were taken from 29 children with acute otitis media, 14 children with chronic sinusitis at acute exacerbation and 2 children with streptococcal pharyngitis who had received cefaclor for 14 days. The study was designed to compare the microbiologic flora of the nasopharynx before the treatment of these diseases with that after the treatment. In this report the subjects were limited to the children who had not received antibiotics within 1 month. Pathogens detected on initial examination were 49 strains consisting of 40 strains of H. influenzae, 3 strains of S. aureus, 5 strains of S. pyogenes, and 1 strain of S. pneumoniae. Two strains were detected in 4 patients. Pathogens remained after treatment in 29 patient, with an unchanged number of pathogens in 12 patients, a decreased number in 14, and microbial substitution in 3. All of the remaining pathogens were H. influenzae, and minimum inhibitory concentration (MIC) changed in 5 of the 26 patients in whom H. influenzae was detected before and after treatment. In a patients with increased MIC, the strain changed from a sensitive strain with an MIC of lower than 3.13 micrograms/ml to a highly resistant strain with an MIC of 25.0 micrograms/ml or higher. By contrast, in 2 patients with decreased MIC, the strain changed from a highly resistant strain with an MIC of 12.5 micrograms/ml or higher to a sensitive strain with an MIC of lower than 3.13 micrograms/ml. In the other patient, MIC decreased to 3.13 micrograms/ml after it had increased from 3.13 micrograms/ml to 25.0 micrograms/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

[Cefaclor dosage change with renal dysfunction].

Serum and/or urine levels of cefaclor (CCL) were studied in 4 patients during the therapy with CCL. In patients with severely impaired renal function, moderately higher serum and urine levels of CCL persisted, serum half-lives of CCL were moderately prolonged and urinary excretion of CCL slightly decreased. Although dosage modification of CCL is necessary in patients with renal dysfunction, multiple doses of 250 mg every 8 hours may be safe and effective even in patients with impaired renal function.

[Clinical studies with minocycline intravenous instillation. Chemotherapy in patients with renal impairment (author's transl)].

In the present studies, we had an opportunity to review the effects of minocycline intravenous instillation for the treatment of moderate disorder of renal functions. No accumulation of minocycline was observed in the repeated administration of this drug instilled intravenously up to 7 days in the patients with moderate disorder of the renal functions. Also, no particular abnormality was observed in the tests of the liver, kidney and hematology. For patients with moderate Ccr 30 approximately 60 ml/min, as entered into the present study, the usual dosage of minocycline intravenous instillation for less than 7 days would not cause adverse reaction on renal functions.