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T Usui

Publications and source records attributed to T Usui.

771 records · Page 43Linked to original sources

Pharmacokinetics of [125I]-recombinant human interleukin-11: 1. Absorption, distribution and excretion after subcutaneous administration to male rats.

Absorption, distribution, metabolism and excretion of [125I]-rhIL-11 (recombinant human interleukin-11) after subcutaneous administration in rats were investigated. After a single administration, the concentration of radioactivity in the tissues was 2-6-fold higher in the liver and kidneys, and slightly higher in the gastrointestinal tract as compared to the plasma concentration. However, since the concentration in the other tissues was lower than the plasma concentration, the transport of rhIL-11 into tissues appeared to be low. Tissue radioactivity rapidly diminished, thus accumulation of rhIL-11 in tissues was thought to be low. Excretion of radioactivity into urine and feces was almost complete 72 h after administration, with 88.5% of the dosed radioactivity being found in urine and 7.9% in feces. When [125I]-rhIL-11 was administered to bile-duct cannulated rats, 44.4% of the dosed radioactivity was excreted into bile up to 48 h after administration. Most radioactivity in bile and urine was found in the TCA supernatant and low molecular weight fraction by HPLC analysis, indicating that rhIL-11 was eliminated from the body by metabolism.

Animals↗

Pharmacokinetics of [125I]-recombinant human interleukin-11: 2. Placental transfer and excretion into milk after subcutaneous administration to rats.

Placental transfer and excretion into milk of [125I]-rhIL-11 (recombinant human interleukin-11) after subcutaneous administration in female rats were investigated. After administration of [125I]-rhIL-11 to rats on the 14th day of gestation, radioactivity in the kidney was the highest among excised tissues, being 3 times higher than that in the plasma at 1.5 h. Radioactivity in other tissues, including the mammary gland, ovary, uterus, placenta and amniotic fluid, was lower than that in the plasma. Although radioactivity in fetuses was detected 6 h after administration, the level was only 2% of the plasma concentration in dams, and the radioactivity was not found in fetal-derived TCA precipitates. These results indicate that rhIL-11 does not readily pass through the placenta into the fetus. After subcutaneous administration of [125I]-rhIL-11 to lactating rats 14 days after delivery, radioactivity in milk was 1.1-1.6 times that in the plasma of dams. Radioactivity in clotted milk in the stomachs of suckling infants was almost equal to that in the dam's milk; however, only a small amount of radioactivity was detected in infant kidneys.

Animals↗

Effects of food deprivation and high fat diet on immunoreactive dynorphin A(1-8) levels in brain regions of Zucker rats.

The levels of immunoreactive dynorphin A(1-8) (ir-DYN8) were measured in discrete brain regions of lean Zucker rats subjected to food deprivation for 72 hr and to a high fat diet, and in fatty Zucker rats after food deprivation for 72 hr. Fatty rats showed higher concentrations of ir-DYN8 in the cortex and midbrain, when compared to lean rats fed a stock diet ad lib. Food deprivation increased ir-DYN8 levels in the cortex of lean rats and fatty rats and in the hippocampus of fatty rats, but decreased its content in the striatum of lean rats and in the midbrain of fatty rats. The high fat diet increased ir-DYN8 levels in the cortex and midbrain of lean rats. These results suggest that ir-DYN8 levels in extrahypothalamic structures of Zucker rats could be differentially modified under conditions of hereditary obesity and dietary manipulations.

Analysis of Variance↗

Pulmonary infection due to anaerobes in a hospital autopsy survey.

Postmortem bacteriologic examination was performed to determine causative organisms in nosocomial or terminal pneumonia for a 10-year period. Most of the patients had severe underlying diseases such as lung cancer (92 cases), leukemia (101), malignant lymphoma (90), and others (85). The materials were obtained by percutaneous aspiration of lung and heart immediately after death or directly from lung and heart after opening the thorax at autopsy. Anaerobic bacteriologic methods were employed for isolation. Twenty-one strains of anaerobic bacteria were recovered (3.4% of the 603 total isolates) from the lungs for 368 cases, and 16 strains (6.5%) of anaerobic bacteria were isolated among 247 strains from heart blood for 314 cases. Bacteroides fragilis was the most frequently isolated anaerobe from both the lungs and heart blood. The same bacterium was isolated from both the lungs and heart blood of four autopsied patients; from three of these patients only B. fragilis was isolated. Enteric gram-negative bacilli and Pseudomonas were common in the patients with nosocomial pneumonia; these patients usually had received many antibiotics before death. The results indicate that anaerobes are not common in fatal nosocomial or other types of pneumonia in the hospital setting, but B. fragilis is relatively important among the anaerobes isolated. However, because of technical considerations, this report must be considered preliminary, and a more definitive study is desirable.

Adult↗

Relationship of thyroid to estramustine binding protein (EMBP) concentration in rat prostate.

Alternations of estramustine binding protein (EMBP) concentration in rat prostate in relation to androgen status under hypo- and hyperthyroid conditions was estimated by means of radioimmunoassay (RIA). In hyperthyroid rats, EMBP concentration in dorsal as well as in lateral prostate was not significantly changed, but significantly reduced in ventral prostate (P less than 0.01). Ventral tissue concentration of testosterone(T) + dihydrotestosterone (DHT), DHT and T, and the ventral tissue ratio of DHT to T + DHT were not significantly changed in hypo- and hyper-thyroid conditions compared with that of the control. In hyperthyroid rats, serum T level and EMBP concentration in ventral prostate were significantly reduced in comparison to ones of the control (P less than 0.05 and P less than 0.01, respectively), however, the ratio of ventral tissue (T + DHT) to serum T was significantly increased (P less than 0.05). Moreover, in contrast to the control, EMBP concentration expressed as microgram/microgram ventral DNA was significantly reduced in hyperthyroid rats (P less than 0.05). On the other hand, in hypothyroid rats, change of EMBP concentration in ventral prostate in relation to androgen status was not significant in comparison to the control. The results here obtained revealed that EMBP concentration in ventral prostate under hyperthyroid condition would be affected by (a) a modulation of endogenous androgen-dependency in EMBP synthesis or by (b) a reduction of cell numbers responsible for EMBP synthesis.

Animals↗

Immunoreactive protein to rat estramustine binding protein in human seminal plasma: its relationship to prostatic acid phosphatase and zinc.

Immunoreactive estramustine binding protein in human seminal plasma obtained from 34 infertile men was measured by means of radioimmunoassay (RIA) using the antibody raised against EMBP obtained from ventral prostate of rat. The mean concentration of IR-EMBP in human seminal plasma measured by this RIA was 1.092 ng/ml, ranging 258 to 1.859 ng/ml. Both concentrations of prostatic acid phosphatase and zinc in human seminal plasma concurrently measured were statistically significantly negatively correlated with that of IR-EMBP. These results here obtained might reveal that IR-EMBP in human seminal plasma signify androgen status in low possibility.

Acid Phosphatase↗

Effect of the growth rate of Pseudomonas aeruginosa biofilms on the susceptibility to antimicrobial agents: beta-lactams and fluoroquinolones.

The growth rate of biofilm bacteria of a leucine-requiring mutant Pseudomonas aeruginosa HU1 was regulated by the leucine concentration in a chemically-defined medium. The semiquantitative measurement of glycocalyx and scanning electron microscopy revealed that the kinetics of HU1-biofilm formation were dependent on the incubation time and the leucine concentration in the medium. The effect of the growth rate of biofilm cells on their susceptibility to antimicrobial agents, three beta-lactams and four fluoroquinolones, was evaluated. beta-Lactams showed weak bactericidal activity to biofilm cells; the activity was greater in younger biofilm cells growing in high concentrations of leucine. Fluoroquinolones revealed strong bactericidal activity to biofilm bacteria regardless of the growth rate. The following is suggested: the bactericidal action of beta-lactams against biofilm cells is affected by the cell growth rate, while that of fluoroquinolones is considerably greater and independent on the growth rate.

Anti-Bacterial Agents↗

Effect of clarithromycin on Pseudomonas aeruginosa biofilms.

Using an experimental in vitro culture system, we investigated the effect of clarithromycin on biofilm formation by a leucine-requiring Pseudomonas aeruginosa mutant strain (HU1). Biofilm formation on celldesks in a chemically defined medium was assessed by viable cell count as well as by measurement of glycocalyx production and scanning electron-microscopic observation. Cells proliferated exponentially until day 3 and remained stationary afterwards. The amount of glycocalyx, simultaneously semiquantified, showed a linear increase from day 1 to day 12. Scanning electron microscopy revealed firm biofilms on day 5. Three different concentrations of Clarithromycin (CAM) (minimum inhibitory concentration MIC 64 microg/ml) were added continuously at the early and late phases of biofilm formation, and the antibiofilm effect of CAM was evaluated by the changes in cell count and glycocalyx production. CAM was effective on biofilms at 100 microg/ml but neither at 1 nor at 10 microg/ml. It is suggested that glycocalyx production started following bacterial multiplication and continued even after the cells had entered the stationary phase to form mature biofilms. No antibiofilm effect of CAM was observed at sub-MIC.

Anti-Bacterial Agents↗

Effect of the growth rate of Pseudomonas aeruginosa biofilms on the susceptibility to antimicrobial agents.

The growth rate of biofilm cells of a leucine-requiring mutant Pseudomonas aeruginosa HU1 was regulated by the leucine concentration in the chemically defined medium, and the effect of the growth rate of biofilm cells on the antimicrobial activities of the antimicrobial agents piperacillin (PIPC), imipenem (IPM) and ofloxacin (OFLX) were evaluated. PIPC showed little effect on the biofilm bacteria regardless of the leucine concentration in the medium. IPM showed weak bactericidal activity to biofilm cells; activity was greater in younger biofilm cells growing in high concentrations of leucine. On the other hand, OFLX revealed strong bactericidal activity to biofilm bacteria regardless of the growth rate. Our data suggest that the bactericidal action of antimicrobial agents to biofilm bacteria is different from that to planktonic bacteria. The bioassay using mutants with regulated growth is useful for the evaluation of the efficacy of antimicrobial agents against biofilm bacteria.

Anti-Bacterial Agents↗

Permeation of antimicrobial agents through Pseudomonas aeruginosa biofilms: a simple method.

In this study, we evaluated the permeation of piperacillin (PIPC), imipenem (IPM), amikacin (AKM), gentamicin (GM), ofloxacin (OFLX), levofloxacin (LVFX), ciprofloxacin (CPFX) and sparfloxacin (SPFX) through Pseudomonas aeruginosa biofilm with a simple new method. Bacteria used were a leucine-requiring mucoid mutant. Bacteria were grown on the membrane of a cell culture insert in chemically defined medium and incubated at 37 degrees C for 5 days. At days 0, 1, 3 and 5, the penetration rates through the biofilms were measured. PIPC and IPM demonstrated relatively high permeation both with penetration rates at day 5 of 50%, whereas AMK and GM, which are aminoglycosides, showed low permeation both with penetration rates after day 1 of less than 25%. Among the 4 fluoroquinolones, LVFX and SPFX demonstrated excellent permeation with penetration rates that reached 100% from day 0 to 5, while OFLX and CPFX showed almost the same permeation as IPM. This method of measuring penetration rates of antimicrobial agents through biofilm is very simple and useful for the evaluation of antibiotics against biofilm-forming bacteria.

Anti-Bacterial Agents↗

Overexpression of human H-ras transgene is responsible for tumors induced by chemical carcinogens in mice.

Level of human prototype H-ras transgene expression in tumors induced by chemical carcinogens (N-ethyl-N-nitrosourea and N-methyl-N-nitrosourea) was analyzed in human H-ras transgenic mice (CB6F1-TgrasH2 Jic mice). All forestomach tumors examined revealed about 2-fold overexpression of the human H-ras transgene with or without point mutation at codon 12 or codon 61. However, endogenous mouse H- and K-ras genes exhibited neither point mutation nor overexpression. These results suggested that increased levels of ras gene products in the cell played an important role in facilitating chemical carcinogenesis in transgenic mice.

Animals↗

Metabolic N-demethylation of 1,3-bis[[1-cycloheptyl-3-(p- dimethylaminophenyl)ureido]methyl]benzene dihydrochloride, a novel acyl-coenzyme A:cholesterol acyltransferase inhibitor.

The metabolism of 1,3-bis[[1-cycloheptyl-3-(p-dimethylamino- phenyl)ureido]methyl]benzene dihydrochloride (YM17E) in rat liver microsomes was investigated. After incubation of YM17E with rat liver microsomes in the presence of NADPH, a significant amount of YM17E was consumed and several products appeared. The structures of these products were identified by thermospray-linked LC/MS. By comparison of fragmentation patterns between these products and authentic compounds, five metabolites were eventually identified. All five metabolites--termed M1, M2-a, M2-b, M3, and M4--were sequentially formed through N-demethylation. The formation of these metabolites was NADPH-dependent, and was inhibited by SKF-525A, metyrapone, and carbon monoxide, which are inhibitors of cytochrome P-450. These results suggest that N-demethylation of YM17E is one of the main pathways of its biotransformation, and that this metabolism is catalyzed by cytochrome P-450-mediated monooxygenase.

Animals↗