Identification of a chromosome harboring the small subunit ribosomal RNA gene of Nosema bombycis.
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Animals↗
Biomedical subjects
R Ishihara
Publications and source records attributed to R Ishihara.
High-yield induction of uterine endometrial adenocarcinomas in Donryu rats by a single intra-uterine administration of N-ethyl-N'-nitro-N-nitrosoguanidine via the vagina.
A total of 130 female Donryu rats (10-week-old) were divided into two groups; 80 animals in the experimental group were given a single intra-uterine administration of 20 mg/kg N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) dissolved in polyethylene glycol (PEG) via the vagina without laparotomy, and 50 animals in the control group received PEG alone in the same manner. Small numbers of animals in both groups were killed at 3, 6, 9 and 12 months after ENNG treatment for sequential histological and endocrinological examination, and at 12.5 experimental months (15 months of age) all survivors were killed. At the termination, endometrial adenocarcinomas were present in 49% of the experimental group, compared to 0% in the control group. Severe endometrial hyperplasias were also found only in the experimental group and sequential histological examination showed first appearance of hyperplasia at 6 months and adenocarcinoma at 9 months. No tumors other than uterine carcinomas were induced by ENNG and the carcinogen treatment did not affect the endocrine environment of rats, persistent estrus appearing at 6 months after the start and increasing with age in both groups. The estradiol-17 beta:progesterone (E:P) ratio was also increased after 6 months, with further elevation at 12 months to about 8 times higher than the level at 6 months. These results indicate that an increased E:P ratio might act as a promoter of development of endometrial proliferative lesions initiated by ENNG in this rat strain. The study indicates that the present simple method using Donryu rats provides a good animal model for endometrial adenocarcinoma development in women.
Adenocarcinoma↗
[Antimicrobial activities of cefditoren against clinical isolates obtained from outpatients].
To examine the antimicrobial activity of cefditoren (CDTR) against strains clinically isolated from outpatients at this hospital from November, 1993 to February, 1994, the minimum inhibitory concentrations (MICs) were determined including those of the control drugs. The results were as follows: 1. CDTR showed strong antimicrobial activities against Staphylococcus aureus subsp. aureus, Streptococcus pyogenes and Streptococcus pneumoniae. The MICs of CDTR against benzylpenicillin-insensitive or -resistant S. pneumoniae distributed in the lowest concentration range even compared to those of the control drugs. 2. CDTR showed strong antimicrobial activities against Haemophilus influenzae, Moraxella subgenus Branhamella catarrhalis, Escherichia coli, and Klebsiella spp. The MIC of CDTR against CEPs-resistant E. coli was lower than those of most control drugs. 3. Since the microbes described above the major pathogens for the community-acquired infections, CDTR will be effective against infectious diseases transmitted at outpatient visits.
Bacteria↗
[Antibacterial activities of new quinolones against fresh clinical isolates].
In order to investigate antibacterial activities of new quinolones (NQs) against a number of clinical isolates obtained in our laboratory during a period from February, 1993 to January, 1994, minimum inhibitory concentrations (MICs) were determined using most of the NQs available in the market as of December, 1993. The obtained results are summarized as follows: 1. Noticeable differences were observed among the antibacterial activities of 8 different NQs tested against Gram-positive bacteria, i.e., there were large differences in their MIC distributions. Some differences were also observed among different NQs in ratios of NQ-resistant strains among Staphylococcus spp. From these results, it seems necessary to further study tolerance mechanisms of these Gram-positive bacteria toward different NQs and also to examine possible differences in antibacterial activities among different NQs against Gram-positive bacteria in clinical settings. 2. MIC distributions against Gram-negative bacteria were also different among the 8 NQs tested. Though elevated MICs were observed against NQ-resistant Gram-negative bacteria in many cases, and somewhat higher, though not exceedingly high, MIC values than those against NQ-sensitive bacteria were found in other cases, patterns of MIC values against different NQ-resistant Gram-negative bacteria were similar for all of the 8 NQs tested. This may explain the fact that most of NQ-resistant Gram-negative bacteria showed similar resistant patterns to the 8 NQs tested. 3. Among the NQ-resistant bacteria, were found Haemophilus influenzae and Neisseria gonorrhoeae strains. Ratios of resistant strains were approximately 10% or lower for the former and approximately 20% for the latter. 4. With MICs of ampicillin and cefaclor used as control, it appears that benzylpenicillin (PCG)-insensitive or PCG-resistant Streptococcus pneumoniae (PISP or PRSP) and CEPs-resistant Escherichia coli are increasing.
4-Quinolones↗
[Antibacterial activities of cefetamet against clinically isolated strains from community acquired respiratory tract infections (II)].
Antibacterial activities of cefetamet (CEMT) against clinically isolated strains from patients with community acquired respiratory tract infections were compared to those of other oral beta-lactam antibiotics in the period from January to March 1994. The following results were obtained. 1. CEMT showed strong antibacterial activities against three major pathogens causing community acquired respiratory tract infections, Streptococcus pyogenes, Streptococcus pneumoniae, and Haemophilus influenzae. However, antibacterial activities of CEMT against benzylpenicillin (PCG)-insensitive S. pneumoniae (PISP) and PCG-resistant S. pneumoniae (PRSP) were slightly weaker than of those of some the reference antibiotics. 2. No MIC value changes of CEMT were observed from year to year against Moraxella subgenus Branhamella catarrhalis and Klebsiella pneumoniae.
Bacteria↗
[Antibacterial activities of isepamicin against fresh clinical isolates of gram-negative bacilli].
To investigate antibacterial activities of isepamicin (ISP), MICs of ISP as well as other aminoglycosides (AGs) were determined against many strains of Gram-negative bacilli that were clinically isolated in 1993. 1. No ISP-resistant strains were observed among isolates of Escherichia coli, Citrobacter diversus, Klebsiella spp., Enterobacter spp. or Proteus mirabilis. 2. ISP-resistant strains were observed among isolates of Citrobacter freundii, Serratia spp., Proteus vulgaris, Morganella morganii, Providencia spp. and Pseudomonas aeruginosa. The frequency of resistant strains in each species, however, was lower for ISP than other AGs. 3. When MIC90s were compared, antibacterial activities of ISP determined in this study were quite similar to those determined during the drug's development period (1980's) in Japan, suggesting no increase in the number of ISP-resistant strains over the years. 4. The number of clinically isolated Gram-negative bacilli resistant to multiple drugs are increasing in from year to year Japan. Our results in this study suggest that antibacterial activities of ISP may be potent enough against such Gram-negative bacilli resistant to multiple drugs.
Drug Resistance, Microbial↗
[Antimicrobial activities of ciprofloxacin against recently obtained clinical isolates].
In order to evaluate antimicrobial activity of ciprofloxacin (CPFX), minimum inhibitory concentrations (MICs) of CPFX and other drugs were determined against clinical isolates that were obtained in our laboratory from January to December of 1991, and of 1993. The results are summarized as follows: 1. CPFX-resistant strains were on the increase in various strains, compared to those in the early 1980s. However, many of CPFX-resistant strains were multi-drug resistant including beta-lactams. In addition, they showed cross resistance to other fluoroquinolone agents. 2. MIC distribution of other drugs suggested that there were increased frequencies of benzylpenicillin (PCG)-insensitive Streptococcus pneumoniae (PISP) and CEPs-resistant Escherichia coli. However, MIC distribution of CPFX to these resistant strains were in a relatively low range. 3. When isolates of 1991 were compared to those of 1993, we confirmed that CPFX-resistant strains decreased among certain bacteria such as Staphylococcus aureus. Also we confirmed that fewer CPFX-resistant strains were found among bacteria that may be highly related to infections encountered in daily medical care.
Bacteria↗
[Antimicrobial activities of fosfomycin against Streptococcus pneumoniae and Haemophilus influenzae recently observed in sinusitis patient].
In order to examine antimicrobial activities of fosfomycin (FOM), the minimum inhibitory concentrations (MICs) of FOM and those of control drugs were determined against Streptococcus pneumoniae and Haemophilus influenzae isolated from sinusitis patients from September to November, 1993, and the following results were obtained. 1. Among 50 S. pneumoniae strains tested, there were 10 strains (20.0%) of benzylpenicillin (PCG)-insensitive S. pneumoniae (PISP) and 2 strains (4.0%) of PCG-resistant S. pneumoniae (PRSP); but the MIC distributions of FOM among the PISPs and the PRSPs were almost identical to those among the PCG-susceptible S. pneumoniae (PSSP). 2. There were 12 strains (24.0%) of beta-lactamase producing strains among 50 strains of H. influenzae tested, but the FOM's MIC distribution among these strains was almost identical to that among beta-lactamase non-producing strains. 3. The results obtained on the MIC90s of FOM against S. pneumoniae and H. influenzae suggest that the nebulization treatment with FOM nasal preparation satisfies the condition "above the MIC".
Drug Resistance, Microbial↗
[Antibiotic efficacies of combined uses of arbekacin and various antibiotics against methicillin-resistant Staphylococcus aureus].
Efficacies of combined uses of arbekacin(ABK) with other antibiotics against between 57 and 76 clinically isolated methicillin-resistant Staphylococcus aureus(MRSA) were examined. Other antibiotics tested were fosfomycin(FOM), 5 cephems(CEPs), 2 penicillins(PCs) and imipenem. Percentages of strains that grew at various combination of serially diluted drugs in a microdilution method were scored, and for each pair of drugs > or = MIC50 or > or = MIC90 was determined. FIC-indices were calculated at > or = MIC50. Bacterial growth was inhibited by low concentrations of ABK dose-dependently, while most of the strains tested were resistant to 9 other drugs. FIC-indices with ABK were lowest when used together with ampicillin (ABPC) (0.516) followed by combinations with cefotiam (CTM) and cefuzonam (CZON) (each, 0.53), and FOM (0.625). When combined with 0.5 microgram/ml of ABK, 0.5 microgram/ml of ABPC inhibited more than 50% of MRSA strains. CTM or CZON in combination with the same amount of ABK to 2 micrograms/ml inhibited more than 50% of MRSA. Thus ABPC was found to be the most efficient in combined use with ABK to inhibit clinical MRSA strains.
Aminoglycosides↗
[Antimicrobial activities of cefteram against recently clinically detected and isolated strains from patients with dental infections].
To investigate the antibiotic activity of cefteram (CFTM), the minimum inhibitory concentrations (MICs) of CFTM and of the control drugs were determined against clinically isolated strains received from November 1991 to April 1993 from 19 dental facilities throughout the country, as well as against clinically isolated strains from samples obtained at this center from patients with dental infectious diseases, and the following results were obtained. 1. 430 strains were detected in 198 cases but identified strains amounted to 425. They are comprised of 204 strains of oral streptococci (48.0%), 81 strains of Peptostreptococcus spp. (19.1%), 10 strains of Bacteroides spp. (2.4%), 23 strains of Prevotella spp. (5.4%), and 9 strains of Porphyromonas spp. (2.1%). The ratios of Gram-positive bacteria v.s. Gram-negative bacteria were 78.4% and 21.6%, respectively, and the Gram-positive bacteria were isolated at higher frequency than Gram-negative bacteria. 2. The MIC90's of CFTM against oral streptococci and Peptostreptococcus spp. were 0.10 microgram/ml and 0.05 microgram/ml, and year to year increases of incidences of resistance against CFTM were not observed. Some strains, however, appeared to have obtained resistance to CFTM. 3. Among Bacteroides spp., Prevotella spp., Porphyromonas spp. which used to belong to genus Bacteroides, there were some strains resistant to CFTM. As a whole, however, no year to year increases in the incidence of CFTM resistance among these strains also. 4. Two strains of 6 Staphylococcus aureus subsp. aureus were methicillin-resistant. 5. The above observations indicate that CFTM still shows strong antimicrobial activity against clinically isolated strains that may be involved in dental infections.
Ampicillin↗
[Antibiotic activities of cefpirome against fresh clinical isolates resistant to multiple drugs].
Using multiple drug-resistant clinical isolates isolated since September 1992, minimum inhibitory concentrations (MICs) of cefpirome (CPR) were determined. Several control drugs were also used, and these MIC-determinations were made to determine the antibiotic activity of CPR. The obtained results are summarized as follows: 1. Antibiotic activities of CPR against methicillin-resistant Staphylococcus spp., Enterococcus faecalis, and benzylpenicillin-insensitive or resistant Streptococcus pneumoniae showed that expanded antibacterial spectrum of CPR and its enhanced antibiotic action against Gram-positive bacteria. We suggest that among the existing fourth-generation cephem antibiotics, CPR is "characteristically strong against Gram-positive bacteria". 2. Strong antibiotic activities of CPR were recognized against bacteria of family Enterobacteriaceae that were resistant to the third-generation cephems. The strong antibiotic activities appeared to be due to CPR's stability and decreased affinity for beta-lactamase. 3. Antibacterial spectrum of CPR was expanded against non-glucose fermented Gram-negative bacilli including Pseudomonas aeruginosa. It appears that this expansion of antibacterial spectrum is due to CPR's affinities for a wide range of penicillin-binding proteins as well as its improved permeability into tissues.
Cephalosporins↗
[beta-lactamase activity in sputum of patients with community-acquired lower respiratory tract infections].
beta-Lactamase production and activities in sputa of patients with community-acquired lower respiratory tract infections (LRTI) were determined and following results were obtained: 1) Suspected causative organisms frequently isolated were H. influenzae and Streptococcus pneumoniae. Similar results were previously reported. 2) Various beta-lactamase producing indigenous bacteria were detected. In many cases these indigenous beta-lactamase producing strains were isolated even when suspected causative bacteria were not beta-lactamase producers. 3) beta-Lactamase activities were detected from 61.5% of the sputa tested. Remaining activities of antibiotics added to the sputa were highly correlated with detection of beta-lactamases produced by suspectedly causative and indigenous strains and with presence of beta-lactamase activities in the sputa. Sulbactam/cefoperazone was stable in sputa than other antibiotics tested. 4) We concluded that the beta-lactamase produced by indigenous strains can be one of the factors of indirect pathogenicity in the community-acquired LRTI.
Cefoperazone↗
[Antimicrobial activities of cefuroxime against recent clinical isolates].
Antimicrobial activity of cefuroxime axetil (CXM-AX) was compared with those of other cephem antibiotics against clinically isolated strains obtained mainly from outpatients of our center in a period from January to September of 1990 and 1993. Minimum inhibitory concentrations were determined and the following results were obtained. 1. The results suggested that, compared with reports of studies conducted with clinical isolates in early 1980's, MIC80 of CXM were equal to or lower against Staphylococcus spp., Streptococcus pyogenes, Escherichia coli, Klebsiella spp., Proteus mirabilis, Haemophilus influenzae, Moraxella subgenus Branhamella catarrhalis, Neisseria gonorrhoeae, Peptostreptococcus spp., and Propionibacterium acnes, except for Streptococcus pneumoniae, MIC80 which was slightly higher. 2. MIC90 of comparator drugs reflected those of new resistant organisms recently appeared, such as benzylpenicillin (PCG)-insensitive S. pneumoniae (PISP), cephem-resistant E. coli and Klebsiella spp., new quinolone-resistant H. influenzae and N. gonorrhoeae. Methicillin-resistant Staphylococcus aureus (MRSA) was detected also from specimens of community acquired infections. From the nature of MRSA detected in those situations MRSA appeared to present a continuing problem. 3. MIC90 against strains obtained from patients with community acquired infections was a good index of increases of multidrug-resistant organisms in the past. Therefore, the determination of MIC90 is important in examining changes with time of sensitivities or resistances of clinically isolated strains to antimicrobial drugs. 4. Antimicrobial activities of CXM against recent clinical isolates showed the existence of problems as mentioned above. However, MIC of CXM as well as those of comparator drugs indicated that antimicrobial activities of CXM against Staphylococcus spp., Streptococcus spp., H. influenzae appeared to be relatively strong, and it is concluded that cefuroxime axetil still is one of the clinically useful oral antimicrobial drugs in the 1990's.
Bacteria↗
[Thirteen-week repeated dose toxicity by oral administration of trandolapril (RU44570) with 4-week recovery test in beagles].
Trandolapril (RU44570) was orally administered to dogs at a daily dose of 2.5, 25 or 250 mg/kg for 13 weeks. After the administration period, 25 and 250 mg/kg groups were observed for recovery for 4 weeks. The results obtained are as follows: 1. One male in the 250 mg/kg group showed decrease of food consumption and body weight, stomatitis, hematemesis, decumbence, hypothermia, and finally loss of reactivity to stimuli. This animal was killed because of these severe changes on the 39th day of administration. Among the surviving animals, a temporary loss of body weight was observed in a few animals of the 25 and 250 mg/kg groups, and a decreased food consumption was sporadically seen in a few animals of the 250 mg/kg group during the administration period. No abnormal changes were found in the clinical observation and water intake in the surviving animals. 2. The changes attributable to the pharmacological effect of RU44570 were a decreased activity of the angiotensin-converting enzyme, increases in plasma renin activity and urine volume, and decreases in specific gravity and concentrations of Na, K and Cl in the urine of every administration group. A decrease in blood pressure and an increase in the PAS and Bowie positive granules in the juxtaglomerular cells were also found in the 25 and 250 mg/kg groups. In addition, thickening of the afferent arteriolar wall of the glomeruli, a basophilic change of the renal tubular epithelial cells, and localized atrophy and hypertrophy of the renal tubules were observed in the 25 and 250 mg/kg groups, and increases in BUN, ALP and creatinine, and a slight dilation of the renal tubules were seen in the 250 mg/kg group. These observations indicated that RU44570 affected renal structure at a dose of 25 mg/kg or more renal function at a dose of 250 mg/kg. The animal killed in a moribund state showed nephrosis which consisted mainly of a moderate dilation of the renal tubules and vacuolation of the renal tubular epithelial cells, stomatitis, severe hemorrhage and necrosis with neutrophil infiltration in the fundus of the glandular stomach, atrophy of the hemopoietic system, and ectopic calcification in the heart, kidneys, stomach, trachea and alveolar wall. Changes in the kidneys similar to those observed in other animals were also detected. These changes suggested that this animal lapsed into a moribund state due to renal dysfunction and the resultant uremia.(ABSTRACT TRUNCATED AT 400 WORDS)
Administration, Oral↗
[Antigenicity study of trandolapril (RU44570)].
Antigenicity of trandolapril (RU44570) was evaluated using the following six standpoints: 1. active systemic anaphylaxis (ASA) in guinea pigs; 2. passive cutaneous anaphylaxis (PCA) in guinea pigs with serum of sensitized guinea pigs; 3. histamine release from lung tissue of sensitized guinea pigs; 4. Schultz-Dale reaction with isolated ileum of sensitized guinea pigs; 5. passive cutaneous anaphylaxis (PCA) in rats with serum of sensitized mice; and 6. delayed type skin reaction by Maximization test in guinea pigs. In the test of immediate type reactions, guinea pigs were sensitized by RU44570 (p.o.), an FCA emulsion of RU44570 (s.c.) or an FCA emulsion of incubate solution of RU44570 and normal guinea pig's serum, and mice were sensitized by a mixture of RU44570 and alum (i.p.). In the test of delayed type reaction, guinea pigs were sensitized by intradermal injection and patch application. 1. ASA in guinea pigs: No anaphylaxis symptoms were observed in any of the sensitized guinea pigs. 2. PCA in guinea pigs: PCA titer of sera from all the sensitized animals was less than 1. 3. Histamine release from lung tissue: No histamine release was observed in any of the isolated lung tissue. 4. Schultz-Dale reaction: No contraction was observed in any of the isolated ileums. 5. PCA in rats: PCA titer of sera from sensitized BALB/c and C3H/He mice was less than 5. 6. Delayed type skin reaction test: No skin reactions were observed in any of the sensitized guinea pigs. From these results, it is concluded that RU44570 has no antigenicity under the conditions of the present study.
Anaphylaxis↗
[Reverse mutation test of trandolapril (RU44570) with bacteria].
Mutagenicity of trandolapril (RU44570) was evaluated by the reverse mutation test with bacteria (test strains used: Salmonella typhimurium TA100, TA98, TA1535, TA1537 and Escherichia coli WP2uvrA). The test was conducted by the preincubation method without metabolic activation (in the absence of S9 mix) and with metabolic activation (in the presence of S9 mix). The number of revertant colonies in the bacterial strains did not exceed twice that obtained in the solvent control either in the presence or absence of S9 mix. There was no dose-dependent increase in the number of revertant colonies observed. Based on the above results, it is concluded that RU44570 has no mutagenicity (gene mutation) under the conditions of the present study.
Angiotensin-Converting Enzyme Inhibitors↗
[Antibacterial activities of cefmenoxime against recent clinical isolates from patients of otitis media and otitis externa].
Bacteria clinically isolated from patients of otitis media and otitis externa were collected from various medical facilities across Japan during years 1988, 1990 and 1992, and minimum inhibitory concentrations (MICs) of cefmenoxime and of reference drugs were determined against these strains. A comparative analyses of the obtained results revealed some trends described below. 1. Methicillin-resistant Staphylococcus aureus (MRSA), multiple drug resistant Coagulase-negative staphylococci (CNS) and multiple drug resistant Proteus spp. showed a year to year trend toward a steady increasing. Relative frequencies of occurrence of MRSA in these years, however, remained comparable to that of early 1980's. 2. A year to year trend toward increasing was also found for resistant or insensitive Streptococcus pneumoniae to penicillins and cephems. 3. Multiple drug-resistant Pseudomonas aeruginosa strains were also detected but they showed no trend toward increasing.
Bacteria↗
[Antimicrobial activity of cefodizime against fresh clinical isolates].
In order evaluate antimicrobial activities of cefodizime (CDZM), minimum inhibitory concentrations (MIC's) of CDZM and other control drugs were determined against various clinical isolates, that were sent to our center from nation-wide medical institutions or were isolated and identified in our laboratory from various specimens of infected patients. The followings are a summary of the results: 1. Bacterial species with no or few strains resistant to cephems including CDZM included Streptococcus pyogenes, Haemophilus influenzae, Citrobacter diversus, most of Klebsiella pneumoniae and Proteus mirabilis. Some strains of Klebsiella oxytoca were resistant to cephems increases in beta-lactams resistant Streptococcus pneumoniae and cephem resistant Escherichia coli seemed likely. Among Citrobacter freundii, Enterobacter spp., Serratia marcescens, Proteus vulgaris, Morganella morganii and Providencia spp. belonging to a category of so-called "mildly toxic bacteria", high portions of the strains examined were resistant to cephems including CDZM and these strains were also resistant to new quinolones, thus they showed multiple drug resistance. 2. MIC90's of CDZM against Streptococcus spp., H. infleunzae, Moraxella subgenus Branhamella catarrhalis, E. coli, Klebsiella spp. and P. mirabilis, frequently found in daily treatment of infections, were less than < or = 0.025 to 1.56 micrograms/ml. This indicates that CDZM would be expected to have enough antibiotic activity in infections caused by above mentioned bacteria. However, cautions are needed in the treatment of infections by beta-lactam resistant S. pneumoniae, cephem resistant E. coli and cephem resistant K. oxytoca with CDZM. 3. Among the above mentioned "mildly toxic bacteria", many multiple drug resistant strains exist. Therefore, we evaluated an usefulness of concomitant use of CDZM with aminoglycosides in the treatment of infections by these bacteria, using other reports which indicates the usefulness in vitro and in vivo. 4. Antibacterial activities of CDZM we observed in this study seem to indicate that CDZM concentrations in infected areas are maintained at above MIC levels for relatively long periods of time.
Bacteria↗