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Biomedical subjects

R Okamoto

Publications and source records attributed to R Okamoto.

At least 127 records · Page 7Linked to original sources

Antimicrobial activity of arbekacin, a new aminoglycoside antibiotic, against methicillin-resistant Staphylococcus aureus.

Arbekacin has excellent antibacterial activity and is also effective against methicillin-resistant Staphylococcus aureus (MRSA) resistant to aminoglycosides such as gentamicin, tobramycin, and methicillin-susceptible Staphylococcus aureus (MSSA). By coagulase typing, four different coagulase types were identified from 358 strains out of 387 MRSA isolated during 1993 in Japan. Among isolates collected in the survey period, about 89% had type 2 coagulase, and only a few had type 3 (4.5%), 4 (2.5%) or 7 (3.6%) coagulase. The distribution of coagulase types in Japan is quite different from those outside Japan which had type 4 coagulase. More than 72% of strains with types 2, 7 and untyped coagulase had high resistance to methicillin. All of the isolates with types 2, 3, 4, and 7 coagulase were highly resistant to gentamicin and tobramycin. 89% of isolates with type 7 coagulase, 2.5% of those with type 2 coagulase and 6.3% of those with type 3 coagulase were found to be arbekacin-resistant. No arbekacin-resistant MRSA was detected among the isolates with type 4 coagulase. In the present study, the authors attempted to determine the strong antibiotic activity of arbekacin against MRSA and particularly gentamicin-resistant MRSA. Arbekacin is not modified by the aminoglycoside-modifying enzyme, ANT (4')-1. Although arbekacin is inactivated by the enzyme APH (2")/AAC (6') which can modify both gentamicin and tobramycin, the rate of modification of arbekacin by this enzyme is only 17% or less of that of gentamicin.

Aminoglycosides↗

Assessment of vitamin E nutritional status in neonates, infants and children--on the basis of alpha-tocopherol levels in blood components and buccal mucosal cells.

We examined the age-related changes of alpha-tocopherol levels in various clinically available biosamples in order to assess the vitamin E nutritional status. During the first week of life, more than half of every sample except red blood cells showed alpha-tocopherol levels below the lower limit of normal in a control group of children aged 3-16 years. alpha-Tocopherol levels in mononuclear leucocytes and buccal mucosal cells, which possess LDL receptors, increased in response to the plasma alpha-tocopherol elevation within a week after birth. However, RBC and platelet levels did not respond so quickly. Considering the transfer of tocopherol into body tissues during LDL catabolism, the determination of tocopherol levels in cells with LDL receptors may be useful for assessing the vitamin E status and our present study suggests that the tissue vitamin E status may be marginal in neonates.

Adolescent↗

Experimental induction of arthritis in rats immunized with Escherichia coli 0:14 lipopolysaccharide.

OBJECTIVE: Escherichia coli 0:14 (E. coli 0:14) induces arthritis in rabbits, mice and rats. This study was designed to investigate the effects of lipopolysaccharide (LPS) on the rat arthritis model induced by systemic injections of E. coli 0:14. METHODS: The induction of arthritis in the ankles of rats immunized by subcutaneous injections with heat-killed E. coli 0:14 and its LPS was studied. The appearance and levels of serum IgM rheumatoid factor-like substance (RFLS) was also investigated. The localization of interleukin 1 (IL-1) and LPS in the ankle joints were investigated immunohistochemically. RESULTS: The induction rate of arthritis in rats immunized with LPS was the same as that in rats immunized with E. coli. LPS and IL-1 were detected in synovial cells, infiltrating cells and some cells on pannus in arthritic joints. Anti-LPS IgM levels in rats immunized with E. coli were as high as those in rats immunized with LPS. RFLS levels in rats immunized with LPS increased more gradually than those in rats immunized with E. coli. CONCLUSION: Our findings suggest that LPS induces arthritis resembling rheumatoid arthritis in rats. The detection of IL-1 in synovial cells in conjunction with LPS suggests that local stimulation of IL-1 production may play an important role in the induction of this experimental arthritis.

Animals↗

[Epidemiological survey of methicillin-resistant Staphylococcus aureus isolated from 34 hospitals in Japan].

Eight hundred and seventy-two isolates of clinically significant methicillin-resistant Staphylococcus aureus (MRSA) with their clinical information were obtained between 1992 and 1993 from thirty-four hospitals in Japan. The isolation frequency of MRSA was high in sputum (42.9%), pus (33.1%) and blood (14.0%). Pseudomonas aeruginosa was a major bacterial species in polymicrobial infections with MRSA. Enterobacteriaceae and Candida sp. were also frequently isolated with MRSA. Four different coagulase types were identified. Coagulase type II was found in 85.6% of all MRSA strains tested. The isolation frequencies of coagulase type III, type IV and type VII were 3.1%, 3.6% and 3.2%, respectively. The strains of MRSA contained coagulase type II were prevalent in all geographical areas of Japan, but other coagulase types were limited in western areas of the country. The strains of MRSA were tested for their susceptibility to twelve antimicrobial agents and for production of penicillinase. More than 80% of MRSA strains were highly resistant to methicillin, and were also resistant to macrolide antibiotics and tobramycin. Frequencies of resistance to gentamicin, minocycline or ofloxacin were approximately 60%, 50% or 70%, respectively. But only a small percentage of strains were resistant to arbekacin and all of the MRSA tested were susceptible to vancomycin.

Anti-Bacterial Agents↗

[Genomic DNA fingerprinting of arbekacin-resistant MRSA by pulsed-field gel electrophoresis].

We surveyed 387 clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) obtained from 26 hospitals isolated in 1993 to determine whether they became resistant to arbekacin (ABK). Twenty-five ABK-resistant MRSA (6.5%) were isolated from 9 hospitals. Analysis of genomic DNA fingerprinting by pulsed-field gel electrophoresis was used to confirm the classification by resistance patterns, phage typing and other biological characters. After digestion with endonuclease SmaI, two or three types of restriction patterns were found in ABK-resistant MRSA isolated from each hospital. We concluded that ABK-resistant MRSA may spread through nosocomial MRSA infections.

Aminoglycosides↗

[Mucormycosis].

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Humans↗

Binding characteristics of antitype II collagen antibody to the surface of diseased human cartilage as a probe for tissue damage.

OBJECTIVE: Studies have shown that collagen type II (CII) on the intact articular surface of cartilage is partially protected from binding to anti-CII antibodies by material proteinaceous in nature, not present in synovial fluid, synthesized by resident chondrocytes, and exquisitely sensitive to polymorphonuclear (PMN) attack and neutrophil elastase digestion. Thus, anti-CII antibody differential binding to articular cartilage surfaces before and after brief neutrophil elastase digestion may be used as a sensitive marker of cartilage damage. METHODS: We measured binding of anti-CII antibodies to the pannus-free articular surfaces of 4 normal, 11 rheumatoid (RA), and 10 osteoarthritic (OA) cartilage specimens, before and after brief digestion with PMN elastase. In addition, antibody binding was quantitated with an antiserum against a 4 M guanidine extract of human cartilage surface. RESULTS: Whereas anti-CII binding increased 59.0% +/- 2.8 after 1 h incubation of normal cartilage with elastase, both the RA and OA specimens failed to show significant increases (RA: 1.0 +/- 0.1; p < 0.001; OA: 27.2% +/- 1.6, p < 0.05). Moreover, anti-CII antibody binding to untreated cartilage specimens was highest for the RA group (Normal: 189.2.1 +/- 38.7 pg anti-lg/mg tissue; RA: 407.5 +/- 80.6, p < 0.05; OA: 243.6 +/- 50.6, NS). Concomitant binding studies with antiserum against cartilage surface material showed greater antibody binding to the articular surfaces than to the cut cartilage surfaces in normal and OA specimens. RA cartilage samples exhibited somewhat smaller antibody binding to the articular surfaces. CONCLUSION: Our studies suggest that in human inflammatory and noninflammatory arthritides the articular cartilage surface undergoes alterations that can be detected by differential binding with anti-CII antibodies, before and after brief digestion with PMN elastase.

Adolescent↗

Cold agglutinin disease following allogeneic bone marrow transplantation.

We describe a case of cold agglutinin disease (CAD) following allogeneic bone marrow transplantation. This 36-year-old male developed CAD 3 weeks after allogeneic bone marrow transplantation for chronic myelogenous leukemia. Cyclosporin A and methotrexate had been administered to prevent graft-versus-host disease. Other agents administered included cytomegalovirus hyperimmune globulin and recombinant human G-CSF. Pericarditis preceded the development of CAD. The characterization of cold agglutinin (CA) was monoclonal IgM-kappa with anti-Pr antigen specificity, probably derived from the engrafted donor lymphocytes. The administration of prednisolone led to transient improvement. The CA titer decreased without further treatment 12 weeks after transplant.

Adult↗

[Drug resistance and phage typing of clinical isolates of Staphylococcus aureus].

Activities of antimicrobial agents were examined against Staphylococcus aureus strains isolated in 1990. Strains resistant to benzylpenicillin were isolated at the highest frequency (93.6%), and followed by those resistant to kanamycin (51.5%), erythromycin (49.0%), gentamicin (45.1%), fluoroquinolone (33.4%) and minocycline (12.3%). Most of these drug resistant strains of S. aureus were also resistant to methicillin. It should be noted that the MRSA strains were also resistant to other multiple drugs. Annual changes of MRSA in clinical isolates have been increasing since 1981. The isolation frequencies of MRSA strains were 18.9%, 44.8% in 1981 and 1990, respectively. Among methicillin susceptible S. aureus (MSSA), however, drug resistance to other antibiotics have been decreasing year by year. Many strains among both MRSA (73%) and MSSA (86%) were sensitive to typing phages of 100 x RTD. 76% of the MRSA strains were phage typed into groups III or mixed, and 60% of the MSSA strains were typed into these two groups, also.

Anti-Bacterial Agents↗

Interference of the blood clot on granulation tissue formation after tooth extraction. Histomorphological study in rats.

The interference of a blood clot in the first postoperative hours of dental extraction wounds was studied in rats. Sixty male albino rats were divided into two groups: Group I, immediately after extraction of right maxillary incisor the gingival mucosa was approximated and sutured; Group II, after 6 to 8 minutes postoperatively the blood clot was removed with saline irrigation and absorbent paper cones. The mucosa was then approximated and sutured. Six animals in each group were sacrificed after 12 hours, 1, 4, 7 and 10 days. There was a profound delay in healing in Group II since, although a new blood clot was later formed, it was not organized. The quality and the constitution, maintenance and retraction of the clot are the regulating factors in connective tissue formation during alveolar healing.

Alveolar Process↗

Energy metabolism of the heart and the liver in brain-dead dogs as assessed by 31P NMR spectroscopy.

The energy metabolism of the heart and the liver was assessed in brain-dead dogs by 31P nuclear magnetic resonance spectroscopy. The mean blood pressure and pulse rate changed respectively from 136.1 +/- 9.3 mm Hg (mean +/- SEM) and 126.7 +/- 4.4/min in the control period, to 212.9 +/- 15.8 mm Hg and 146.7 +/- 13.3/min during Cushing phenomenon (CU period), and to 60.0 +/- 6.4 mm Hg and 60.0 +/- 2.9/min after completion of brain death (BD period). The ratio of creatine phosphate to inorganic phosphate (PCr/Pi) of the heart decreased from 5.00 +/- 1.08 to 3.24 +/- 0.80 in the CU period and increased to the levels of the control values in the early BD period. The intracellular pH of the heart decreased from 7.20 +/- 0.07 to 6.91 +/- 0.02 in the CU period and increased to 7.12 +/- 0.01 in the BD period. The positive relationship between the Pi/PCr and the rate-pressure product (BP x PR) indicates that the regulation of the oxidative metabolism by free ADP was well maintained except at some points in the CU period (Pi/PCr = 8.77 x 10(-6) BP x PR + 0.164, r = 0.704). This suggested that the remarkable hypotension and bradycardia in the BD period is not associated with cardiac energy failure. Although the energy states of both the heart and the liver in brain-dead dogs were adequately maintained in the BD period, the changes were different.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

Basic fibroblast growth factor (bFGF) receptors decrease with luteal age in rat ovarian luteal cells: colocalization of bFGF receptors and bFGF in luteal cells.

Ovarian growth factors have been implicated in the development and differentiation of corpus luteum. We have characterized both high and low affinity receptors for basic fibroblast growth factor (bFGF) in luteal cells and tissue throughout the life span of corpus luteum using gonadotropin-treated rat luteinized ovaries. Additionally, we determined bFGF location in luteal tissue. High affinity (Kd, approximately 0.2 nM) and low capacity (approximately 500-6000 sites/cell, depending on luteal ages) [125I] bFGF-binding sites (mol wt, 140 kilodaltons, determined by affinity labeling) were found on luteal cells. [125I]bFGF binding to luteal cells and corpus luteum membranes progressively decreased in binding capacity without affecting binding affinity as the age of corpus luteum advanced. bFGF receptor (flg) mRNA in luteinized ovaries decreased with the luteal age similar to the [125I]bFGF binding. In contrast, low affinity binding sites, identified as heparan sulfate proteoglycans, which were immunohistochemically visualized around luteal cells, did not appear to change with luteal age. The signals for heparan sulfate proteoglycans that were found only in granulosa, but not theca-interstitial, cells of follicles became intense during folliculogenesis. The functionality of the bFGF receptors was shown by tyrosine phosphorylation of 16.5- and 18-kilodalton proteins in luteal cells with the antiphosphotyrosine antibody. Immunohistochemistry localized bFGF to steroidogenic luteal cells, and immunoblotting displayed larger molecular forms of bFGF in luteal cells. These results suggest that the bFGF receptors may be associated with the development and differentiation of corpus luteum in an autocrine manner.

Animals↗

Cloning and nucleotide sequences of two genes involved in the 4''-O-acylation of macrolide antibiotics from Streptomyces thermotolerans.

A DNA fragment responsible for the 4''-O-acylation of macrolide antibiotics was cloned from a mutant strain of the carbomycin producer Streptomyces thermotolerans. The gene encoding the macrolide 4''-O-acyltransferase was within a 2.7-kb region of the cloned fragment (15-kb). Streptomyces lividans carrying the region converted exogenously added tylosin to 4''-O-acyltylosins. Nucleotide sequencing of the region showed two open reading frames (ORFs). Expression assay using deleted plasmids showed that both ORFs were essential for optimal expression of the acyltransferase activity. One of them (acyB1) was identical with carE reported previously as a gene encoding 4''-mycarosyl isovaleryl-CoA transferase. The other (acyB2) was assumed to encode a novel regulatory protein that could active acyB1 expression. acyB1 and acyB2 were highly conserved among streptomycetes with macrolide 4''-O-acyl transferase activity.

Acylation↗

Effect of beta-endorphin on cAMP and progesterone accumulation in rat luteal cells.

The aim of this study is to investigate the effect of beta-endorphin on cAMP and progesterone accumulation in rat luteal cells. Luteal cells of 4-day-old corpora lutea were cultured for 3 h in the absence or presence of 0.001 or 0.01 IU/ml hCG, and cAMP, progesterone and beta-endorphin levels in the medium were measured by RIA. hCG stimulated the production of cAMP, progesterone and beta-endorphin. In the presence of hCG, treatment with islet-activating protein (IAP) led to overall augmentation of cAMP and progesterone accumulation in comparison with untreated controls. In the absence or presence of low doses of hCG (0.001 IU/ml), beta-endorphin did not affect progesterone production, but inhibited cAMP accumulation. This inhibitory effect was abolished by pre-treatment with IAP. In the presence of high doses of hCG (0.01 IU/ml), however, beta-endorphin stimulated progesterone production without a corresponding increase in cAMP. This stimulatory effect was also abolished by IAP-treatment. These results suggest that luteal cells produce and release beta-endorphin that affects cAMP and progesterone production via IAP-sensitive mechanisms.

Animals↗

Microbial glycosidation of some anthracycline antibiotics by an antibiotic-negative mutant of aclarubicin producer.

Microbial conversion of anthracyclinone monosaccharides using aclarubicin-negative mutant of Streptomyces galilaeus was found to produce anthracyclinone disaccharides which had either rhodinose or 2-deoxyfucose as an additional sugar. By this conversion we obtained twelve new anthracyclines from seven anthracyclines which had rhodosamine, N-monomethyldaunosamine or daunosamine at C-7 as a glycosidic sugar. All products had a reduced cytotoxic activity in comparison with those of parent compounds. However, some of them showed a therapeutically improved antitumor effects against L1210 leukemia in vivo.

Aclarubicin↗

Enzymatic dimerization of penicillin X.

Penicillin X methyl ester was transformed into three types of dimer by laccase from Coriolus versicolor. The dimers are considered to be formed by free-radical addition of phenoxy radicals produced by laccase. The enzyme reaction with the ester as substrate was more suitable for forming dimers than that with the sodium salt as substrate. Penicillin X pivaloyloxymethyl ester was also transformed into a dimer, which had antibacterial activity in the presence of esterase.

Anti-Bacterial Agents↗