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Biomedical subjects

M Kaku

Publications and source records attributed to M Kaku.

At least 73 records · Page 4Linked to original sources
PubMed1999

[Clinical and bacteriological effects of cefetamet pivoxil against community-acquired respiratory tract infections. Part III].

We investigated clinical and bacteriological effects of cefetamet pivoxil (CEMT-PI) on community-acquired respiratory tract infection and obtained the following results: This method of investigation was almost the same to those adopted in 1994 and 1996. 1. 512 cases of respiratory tract infection were treated with CEMT-PI under the same protocol at a total of 53 institutions in Tokyo, Kanagawa, Saitama, Chiba and Yamanashi prefectures from January, 1, 1998 over March, 31, 1998. Outpatients accounted for 99.7% of all subjects. Diagnoses given to these patients included pharyngolaryngitis (51.4%), tonsillitis (37.7%), and acute bronchitis (10.1%). 2. For the bacteriological study, a manual detailing the method of collecting specimens, storage and transport was distributed to the above-mentioned institutions. The isolation and identification of suspected causative bacteria, determination of minimum inhibitory concentrations (MICs), and investigation of beta-lactamase production were conducted all together at Section of Studies, Tokyo Clinical Research Center. Suspected causative bacteria were detected in 144 (37.2%) out of 387 cases that were the analytical subjects of the clinical efficacy. The major bacteria identified were 32 strains of Streptococcus pyogenes and 19 strains of Haemophilus influenzae. The clinical efficacy (the ratio of improvement) of CEMT by suspected causative bacterium was 84.4% against CEMT-indicated organisms and 81.2% against CEMT-non-indicated organisms. 3. We investigated clinical efficacy rates (the ratio of "markedly improved" + "improved") by disease. The improvement rate was 78.4% in pharyngolaryngitis, 87.0% in tonsillitis, and 79.5% in acute bronchitis. The clinical efficacy rate was an average of 81.9% in all CEMT-PI indicated diseases.

Adult↗
PubMed1999

[Detection of K-ras mutations in colon cancer by PHA-PHFA (preferential homoduplex formation assay)].

The mutations of K-ras gene have been demonstrated at frequencies of about 40% in human colorectal cancer. We applied a developed PCR-preferential homoduplex formation assay (PCR-PHFA) to detect a point mutation of K-ras gene in the surgical specimens from thirty patients with colorectal cancer. This method is based on the strand competition during hybridization between a double labeled amplicon, prepared from biotin and DNP labeled primers, and an unlabeled amplicon. The procedure of this method is simple and speedy, and suitable to detect mutations in a small number of samples. By using this method, the mutations were found in 37% (11/30) and confirmed by sequencing analysis. The results suggest that the PCR-PHFA system may be useful for detecting low frequent mutation of K-ras gene even in the case of an early cancer.

Colorectal Neoplasms↗
PubMed1999

Role of human parvovirus B19 in the pathogenesis of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease of unknown origin. It has been speculated that infectious agents are responsible for triggering RA. Persistent infection with human parvovirus B19 and its induction of immunopathology are hypothesized to explain the initiation and perpetuation of the disease process.

Arthritis, Rheumatoid↗
PubMed1998

Homozygous missense mutation (band 3 Fukuoka: G130R): a mild form of hereditary spherocytosis with near-normal band 3 content and minimal changes of membrane ultrastructure despite moderate protein 4.2 deficiency.

The characteristics of phenotypic expression were studied in a Japanese family with hereditary spherocytosis and an extremely rare homozygous missense mutation of the band 3 gene (band 3 Fukuoka: G130R). The homozygous unsplenectomized proband was a 29-year-old male with compensated haemolytic anaemia (red cell count 4.21 x 10(12)/l, reticulocytes 278 x 10(9)/l, and indirect bilirubin 44 micromol/l). His red cell band 3 (B3) protein demonstrated a 9.3% reduction and his protein 4.2 (P4.2) level was substantially reduced (45.0%), compared to normal subjects. P4.2 protein was composed mostly of a wild type (72 kD) with a trace of 68 kD peptide. The binding properties of the mutated B3 to normal P4.2 were significantly impaired, which probably resulted in the substantial reduction of P4.2 in this proband, since no abnormalities were detected on the P4.2 gene. Electron microscopy (EM) using the freeze-fracture method demonstrated a mild decrease in intramembrane particles (IMPs) of near-normal size (8 nm in diameter) with no substantial increases in their oligomerization. Their distribution on the membrane P face was almost normal, although most of the IMPs could represent the homozygously mutated B3 protein. EM (quick-freeze deep-etching method) disclosed a skeletal network of near-normal size and size distribution of the skeletal units, suggesting that the mutated B3 protein itself did not have much effect on the skeletal network in situ. Therefore the reduced P4.2 content (45% of that of normal subjects), which remained on the red cell membrane of this proband, appeared to be nearly sufficient for maintaining the normal structure of the skeletal network and IMPs in situ, contrary to the marked abnormalities in both IMPs and the skeletal network in complete P4.2 deficiencies.

Adult↗
PubMed1998

Escherichia coli O157 interactions with human intestinal Caco-2 cells and the influence of fosfomycin.

It is not clear how Escherichia coli O157 invades human enteric epithelium and causes the haemolytic uraemic syndrome (HUS), and nor has the most appropriate treatment of E. coli O157 infection been established. Verotoxins, leucocytes and proinflammatory cytokines, such as tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-6 and IL-8, are considered essential for the development of HUS. We used the Caco-2 cell monolayer system, well-known as an in-vitro model of human intestinal infection, to determine how E. coli O157 interacts with intestinal epithelial cells and also studied the influence of fosfomycin on the virulence of the bacteria. Results showed that the E. coli O157 used in this study did not penetrate the Caco-2 cell monolayer system, unlike Salmonella typhimurium SL1344, and verotoxin 1 (VT 1), but not VT 2, translocated across the system. In an in-vitro conventional assay, fosfomycin increased the amount of verotoxins but it did not influence penetration of bacteria and translocation of verotoxins in the Caco-2 cell monolayer system. The production of both IL-8 (a potent neutrophil activator) and TNF-alpha in the human monocytic THP-1 cell line was reduced by fosfomycin-treated basolateral medium in this system. These results indicate that fosfomycin may be a potent drug for preventing HUS caused by E. coli O157 infection.

Anti-Bacterial Agents↗
PubMed1998

In vitro activities of quinupristin-dalfopristin and the streptogramin RPR 106972 against Mycoplasma pneumoniae.

The in vitro activities of quinupristin-dalfopristin and streptogramin RPR 106972 were determined with 44 strains of Mycoplasma pneumoniae and compared to those of macrolides, minocycline, and quinolones. All isolates tested were highly susceptible to macrolides and to quinupristin-dalfopristin (MIC at which 90% of the isolates are inhibited [MIC90], 0.0625 microg/ml), followed by RPR 106972 (MIC90, 0.5 microg/ml), quinolones, and minocycline.

Anti-Bacterial Agents↗
PubMed1998

Rapid detection and evaluation of clinical characteristics of emerging multiple-drug-resistant gram-negative rods carrying the metallo-beta-lactamase gene blaIMP.

Gram-negative rods (GNR) carrying the transferable carbapenem resistance gene blaIMP, including Pseudomonas aeruginosa and Serratia marcescens, have been isolated from more than 20 hospitals in Japan. Although the emergence of such multiple-drug-resistant bacteria is of utmost clinical concern, little information in regard to the distribution of blaIMP-positive GNR in hospitals and the clinical characteristics of infected patients is available. To address this, a system for the rapid detection of the blaIMP gene with a simple DNA preparation and by enzymatic detection of PCR products was developed. A total of 933 ceftazidime-resistant strains of GNR isolated between 1991 and 1996 at Nagasaki University Hospital, Nagasaki, Japan, were screened for the blaIMP gene; 80 isolates were positive, including 53 P. aeruginosa isolates, 13 other glucose-nonfermenting bacteria, 13 S. marcescens isolates, and 1 Citrobacter freundii isolate. Most of the patients from whom blaIMP-positive organisms were isolated had malignant diseases (53. 8%). The organisms caused urinary tract infections, pneumonia, or other infections in 46.3% of the patients, while they were just colonizing the other patients evaluated. It was possible that blaIMP-positive P. aeruginosa strains contributed to the death of four patients, while the other infections caused by GNR carrying blaIMP were not lethal. DNA fingerprinting analysis by pulsed-field gel electrophoresis suggested the cross transmission of strains within the hospital. The isolates were ceftazidime resistant and were frequently resistant to other antibiotics. Although no particular means of pathogenesis of blaIMP-positive GNR is evident at present, the rapid detection of such strains is necessary to help with infection control practices for the prevention of their dissemination and the transmission of the resistance gene to other pathogenic bacteria.

DNA Fingerprinting↗
PubMed1998

Midpalatal suture of osteopetrotic (op/op) mice exhibits immature fusion.

The midpalatal suture was observed histologically in both toothless osteopetrotic (op/op) and normal (control) mice. The normal mice had a mature sutural structure, which consists of a well-developed cartilage cell zone and palatal bone. In contrast, the thickness of the cartilage cell zone was substantially greater in the op/op mice than that in the controls. Moreover, the cartilage cells in the op/op mice were frequently found in the palatal bone as well as in the sutural space, exhibiting an imperfect fusion. It seems that immature fusion at the sutural interface in the op/op mice is related to a decrease in biting or masticatory force accompanied by the failure of tooth eruption in addition to an essential defect in osteoclast differentiation, which is a congenital symptom in op/op mice.

Animals↗
PubMed1998

Suspension "hypokinesia/hypodynamia" may decrease bone mass by stimulating osteoclast production in ovariectomized mice.

This study was conducted to examine, in detail, the histological changes in the femurs of suspended ovariectomized (OVX) mice to assess the role of mechanical stress on bone remodeling. Suspended-OVX, suspended-sham-ope, nonsuspended-OVX, and nonsuspended-sham-operated mice underwent operations 8 weeks after birth. Immediately after operation, hypokinesia/hypodynamia was created by a suspension harness for one week. Five specimens in each group were sacrificed 9 weeks after birth. The trabecular bone of the femurs in the suspended-OVX mice was removed and replaced extensively by bone marrow. The number of tartrate-resistant acid phosphatase (TRAP)-positive cells was larger in the suspended-OVX mice than in the remaining three groups. No significant differences in the number of TRAP positive cells were found between the suspended-sham-ope, nonsuspended-OVX and nonsuspended-sham-ope mice. The femurs of the OVX mouse with suspension "hypokinesia/hypodynamia" thus exhibits extensive trabecular bone loss in association with an increase of osteoclasts.

Acid Phosphatase↗
PubMed1998

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1996). I. Susceptibility distribution].

The frequencies of isolation and susceptibilities to antimicrobial agents were investigated on 680 bacterial strains isolated from patients with urinary tract infections (UTIs) in 10 hospitals during the period of June 1996 to May 1997. Of the above bacterial isolates, Gram-positive bacteria accounted for 30.4% and a majority of them were Enterococcus faecalis. Gram-negative bacteria accounted for 69.6% and most of them were Escherichia coli. Susceptabilities of several isolated bacteria to antimicrobial agents were as followed; 1. Enterococcus faecalis Ampicillin (ABPC) showed the highest activity against E. faecalis isolated from patients with UTIs. Its MIC90 was 1 microgram/ml. Imipenem (IPM) and vancomycin (VCM) were also active with the MIC90S of 2 micrograms/ml. The others had low activities with the MIC90S of 16 micrograms/ml or above. 2. Staphylococcus aureus including MRSA Arbekacin (ABK) and VCM showed the highest activities against both S. aureus and MRSA isolated from patients with UTIs. The MIC90S of them were 1 or 2 micrograms/ml. The others except minocycline (MINO) had low activities with the MIC90S of 32 micrograms/ml or above. 3. Staphylococcus epidermidis ABK and VCM showed the strongest activities against S. epidermis isolated from patients with UTIs. The MICs for all strains were equal to or lower than 2 micrograms/ml. Cefazolin (CEZ), cefotiam (CTM) and cefozopran (CZOP) were also active with the MIC90S of 4 micrograms/ml. Compared with antimicrobial activities of cephems is 1995, the MIC90S of them had changed into a better state. They ranged from 4 micrograms/ml 16 micrograms/ml in 1996. 4. Streptococcus agalactiae All drugs except MINO were active against S. agalactiae. ABPC, CZOP, IPM, and clarithromycin (CAM) showed the highest activities. The MICs for all strains were equal to or lower than 0.125 micromilligrams. Tosufloxacin (TFLX) and VCM were also active with the MIC90S of 0.5 micromilligrams. 5. Citrobacter freundii Gentamicin (GM) showed the highest activity against C. freundii isolated from patients with UTIs. Its MIC90 was 0.5 micrograms/ml. IPM and amikacin (AMK) were also active with the MIC90S of 1 microgram/ml and 2 micrograms/ml, respectively. Cefpirome (CPR) and CZOP were also active with the MIC90S of 8 micrograms/ml. The MIC90S of the others were 16 micrograms/ml or above. 6. Enterobacter cloacae IPM showed the highest activity against E. cloacae. The MICs for all strains were equal to or lower than 0.5 microgram/ml. The MIC90S of ciprofloxacin (CPFX) and TFLX were 1 microgram/ml, the MIC90 of AMK was 2 micrograms/ml, the MIC90S of CZOP, GM and ofloxacin (OFLX) were 4 micrograms/ml. The MIC50S of cephems except CEZ, cefmetazole (CMZ) and cefaclor (CCL) had changed into a better state in 1996, compared with those in 1995. 7. Escherichia coli All drugs except penicillins and MINO were active against E. coli. Particularly CPR, CZOP and IPM showed the highest activities against E. coli. The MIC90S of them were 0.125 microgram/ml or below. Among E. coli strains, those with low susceptibilities to cephems except CEZ, cefoperazone (CPZ), latamoxef (LMOX) and CCL have increased in 1996, compared with those in 1995. 8. Klebsiella pneumoniae K. pneumoniae was susceptible to all drugs except penicillins, with the MIC90S of 2 micrograms/ml or below. CPR had the strongest activity, the MICs for all strains were equal to or lower than 0.25 microgram/ml. Flomoxef (FMOX), cefixime (CFIX), CZOP and carumonam (CRMN) were also active with the MIC90S of 0.125 microgram/ml or below. 9. Pseudomonas aeruginosa All drugs except quinolones were not so active against P. aeruginosa with the MIC90S were 32 micrograms/ml or above. Quinolones were more active in 1996 than 1995. The MIC90S of them were between 4 micrograms/ml and 8 micrograms/ml, and the MIC50S of them were between 1 microgram/ml and 2 micrograms/ml. 10. Serratia marcescens GM showed the highest activity against S. marcescens. Its MIC90 was 1 micro

Anti-Bacterial Agents↗
PubMed1998

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1996). II. Background of patients].

Clinical background was investigated on patients with urinary tract infections (UTIs) from whom 752 bacterial strains were isolated in 10 hospitals during the period from June, 1996 through May, 1997. 1. Distribution of age and sex of patients and type of infections. Among males, those with ages 40 years or older were more frequent, the higher the ages of them. Among females, those with ages in the 60's were the most frequent (24.6%), and those with ages in the 20's, 40's and 50's were about 13%. With regard to type of infections, more than a half of infections among males with ages 30 years or older were of complicated types, but most of infections among females were of uncomplicated types, especially among females of ages less than 60 years. 2. Ages of patients and types of pathogens. The higher the ages of patients, the lesser became the isolation frequencies of Escherichia coli, but the higher were those of Pseudomonas aeruginosa and Klebsiella spp. 3. Effect of antibiotic use on isolation frequencies of pathogens. Use of antibiotics decreased pathogens isolated from patients with uncomplicated UTIs drastically (231 isolates before antibiotics compared to 60 after). Even isolated pathogens from patients with complicated UTIs decreased drastically with the use of antibiotics when indwelling catheters were not in use (193 isolates before antibiotics compared to 75 after), but when indwelling catheters were in use, antibiotics apparently failed to decrease the isolation frequency. 4. Surgical procedures and types of causative organisms for UTIs. From cases of uncomplicated UTIs, E. coli was the most frequently isolated, followed by Enterococcus Faecalis and Klebsiella spp. E. coli was the most frequently isolated organism from complicated UTIs without indwelling catheters. When a surgical procedures were not done, E. coli was isolated most frequently. From cases of complicated UTIs with indwelling catheters, P. aeruginosa, E. coli and E. faecalis were the organisms that were mainly isolated, with isolation frequencies of 23.2%, 15.2, 12.2, respectively. When no surgical procedures were used, isolation frequencies of P. aeruginosa, E. faecalis and Enterobacter spp. were 17.2%, 13.8%, 13.8%, respectively.

Adolescent↗
PubMed1998

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1996), III. Secular changes in susceptibility].

Susceptibilities to various antimicrobial agents were examined for Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Klebsiella spp., and Pseudomonas aeruginosa that were isolated from patients with urinary tract infections (UTIs) in 10 hospitals during June 1996 to May 1997, and the results were compared with those obtained during the same period in earlier years. 1. E. faecalis Among E. faecalis strains, those with high susceptibilities to ampicillin and minocycline appeared to have decreased in the latest study period. 2. S. aureus To almost antimicrobial agents, S. aureus isolated from uncomplicated UTIs showed low susceptibilities. But the MIC50s of those agents for S. aureus from complicated UTIs have changed better state. Particularly, the MIC50s of imipenem and clindamycin were 0.125 microgram/ml or below in the latest period for the first time in our history. 3. E. coli The susceptibilities to piperacillin and quinolones of E. coli isolated from uncomplicated UTIs were better than those isolated from complicated UTIs. 4. Klebsiella spp. The susceptibilities to almost antimicrobial agents of Klebsiella spp. have been better during the latest period, compared to those during period of 1995-1996, but to ofloxacin and ciprofloxacin have appeared to have been lower. 5. P. aeruginosa The susceptibilities to quinolones of P. aeruginosa have been better during the latest period compared those during periods of 1995-1996. But, the susceptibilities to cefozopran, carbapenems and monobactams of P. aeruginosa isolated from complicated UTIs appeared to have been lower. These susceptibility changes should be utilized in determining clinical treatments.

Anti-Bacterial Agents↗
PubMed1997

Genetic relationship of penicillin resistant Streptococcus pneumoniae serotype 19B strains in Japan.

Pulsed field gel electrophoresis (PFGE) of the genomic DNA of penicillin resistant serotype 19B Streptococcus pneumoniae was carried out. Thirteen strains form the Nagasaki area and 12 strains from other areas in Japan were examined. Twenty-three strains were resistant to erythromycin, tetracycline and trimethoprim/sulfamethoxazole but susceptible to chloramphenicol. Eight strains were resistant to ceftriaxone. All strains were multiply resistant. Five strains isolated from Nagasaki were indistinguishable from each other by using restriction enzymes Apa I and Sma I. Two strains isolated from other areas were indistinguishable from the above five strains. We could classify 13 Nagasaki strains into 3 groups and the total of 25 Japanese strains into 6 groups. These results suggest that the increasing prevalence of multiply drug resistant S. pneumoniae serotyped 19B in Japan is not due to a single clone, but at least one clone has spread widely in Japan.

DNA, Bacterial↗
PubMed1997

In vitro susceptibility studies and detection of vancomycin resistance genes in clinical isolates of enterococci in Nagasaki, Japan.

Glycopeptide resistance in enterococci is now a cause of clinical concern in the United States and Europe. However, details of vancomycin resistance in enterococci in Japan have been unknown. We measured minimum inhibitory concentrations (MICs) of various antimicrobial agents for a total of 218 clinical strains of enterococci isolated in our hospital in 1995-6 in addition to 15 strains with known genotypic markers of resistance. We also screened vancomycin resistance genes using a single step multiplex-PCR. In clinical isolates, only two strains of Enterococcus gallinarum were of intermediate resistance to vancomycin (MIC, 8 micrograms/ml), while the others were all susceptible. Glycopeptides (vancomycin and teicoplanin) and streptogramins (RP 58500 and RPR 106972) showed potent antimicrobial effects for the isolates. In addition, ampicillin was also potent for Enterococcus faecalis, while ampicillin, minocycline and gentamicin were potent for Enterococcus avium. No vanA or vanB genes were detected, while vanC1 and vanC23 genes were detected from two and four strains, respectively. Our results suggest that incidence of VRE in Japan may be estimated as still very low at this time.

Anti-Bacterial Agents↗
PubMed1997

Role of coagulase in a murine model of hematogenous pulmonary infection induced by intravenous injection of Staphylococcus aureus enmeshed in agar beads.

We describe a novel mouse model of acute staphylococcal pneumonia induced by intravenous injection of Staphylococcus aureus enmeshed in agar beads. For comparison, we also used various strains of bacteria, including three strains of S. aureus, two strains of Staphylococcus epidermidis, one strain of Streptococcus pyogenes, three strains of Pseudomonas aeruginosa, and one strain of Klebsiella pneumoniae. All except two strains of S. aureus were cleared rapidly from the lungs. When S. aureus NUMR1 enmeshed in agar beads was injected intravenously, the organisms concentrated and remained in the lung for a period longer than several weeks. Multiple lung abscesses were evident macroscopically, and histological examination of the infected lung showed multiple lung abscesses around the pulmonary arterioles, consisting of bacterial colonies encircled with fibrin filaments and surrounded by inflammatory cells of neutrophils and macrophages. When 14 strains of clinically isolated S. aureus were injected intravenously, the number of bacteria recovered from the lung tissue 7 days after infection correlated with the titer of staphylocoagulase (P < 0.01) but not with the titer of clumping factor. Injection of coagulase-deficient mutant strain DU5843 was associated with a markedly reduced number of viable bacteria isolated from the lung, compared with its coagulase-positive parental strain DU5789. Our results suggest that coagulase may play a role in the development of blood-borne staphylococcal pneumonia in our model. Our animal model is simple and reproducible and resembles blood-borne staphylococcal pneumonia in humans, and it could be useful for investigating the pathogenicity or treatment of staphylococcal pulmonary infection, including infections with methicillin-resistant S. aureus.

Agar↗
PubMed1997

An improved assay method for fibroblast gelatinolytic enzyme.

A useful gelatinolytic enzyme assay for fibroblasts, utilizing a novel sample preparation method for collagenase with dithiothreitol (DTT) treatment to inactivate endogenous collagenase inhibitors, was developed using soluble fluorescein isothiocyanate (FITC)-labeled gelatin. The substrate, gelatin was prepared by heating commercially available FITC-labeled type I collagen. The denatured collagen was cleaved with purified trypsin and partially purified fibroblast gelatinase, and the digested FITC-fragments were measured fluorometrically. The intensity of the fluorescence was in proportion to the reaction time and enzyme concentration. Both enzyme activities were measurable within the nanogram range of enzyme preparations. The enzyme activity was detected after 4-aminophenylmercuric acetate (APMA) treatment which was completely inhibited by metalloproteinase inhibitors, but not by serine- and cysteine-proteinases' inhibitors. Conditioned media of human periodontal ligament fibroblasts (PLF) and gingival fibroblasts (GF) were separately treated with DTT prior to the enzyme assay, and then the assay was performed in the presence of APMA. The enzyme activities of PLF and GF were 106- and 55-fold higher than those of the conventional gelatinase assay which was carried out without DTT treatment. This assay method allowed the measurement of gelatinolytic enzyme activity when tissue inhibitors of metalloproteinases were present in the fibroblast culture medium.

Biological Assay↗