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Mitsuo Kaku

Publications and source records attributed to Mitsuo Kaku.

At least 19 recordsLinked to original sources
PubMed2006

Outbreaks of multidrug-resistant Pseudomonas aeruginosa in community hospitals in Japan.

We previously reported an outbreak in a neurosurgery ward of catheter-associated urinary tract infection with multidrug-resistant (MDR) Pseudomonas aeruginosa strain IMCJ2.S1, carrying the 6'-N-aminoglycoside acetyltransferase gene [aac(6')-Iae]. For further epidemiologic studies, 214 clinical isolates of MDR P. aeruginosa showing resistance to imipenem (MIC >or= 16 microg/ml), amikacin (MIC >or= 64 microg/ml), and ciprofloxacin (MIC >or= 4 microg/ml) were collected from 13 hospitals in the same prefecture in Japan. We also collected 70 clinical isolates of P. aeruginosa that were sensitive to one or more of these antibiotics and compared their characteristics with those of the MDR P. aeruginosa isolates. Of the 214 MDR P. aeruginosa isolates, 212 (99%) were serotype O11. We developed a loop-mediated isothermal amplification (LAMP) assay and a slide agglutination test for detection of the aac(6')-Iae gene and the AAC(6')-Iae protein, respectively. Of the 212 MDR P. aeruginosa isolates, 212 (100%) and 207 (98%) were positive in the LAMP assay and in the agglutination test, respectively. Mutations of gyrA and parC genes resulting in amino acid substitutions were detected in 213 of the 214 MDR P. aeruginosa isolates (99%). Of the 214 MDR P. aeruginosa isolates, 212 showed pulsed-field gel electrophoresis patterns with >or=70% similarity to that of IMCJ2.S1 and 83 showed a pattern identical to that of IMCJ2.S1, indicating that clonal expansion of MDR P. aeruginosa occurred in community hospitals in this area. The methods developed in this study to detect aac(6')-Iae were rapid and effective in diagnosing infections caused by various MDR P. aeruginosa clones.

Acetyltransferases↗
PubMed2006

Expression analyses and transcriptional regulation of mouse nucleolar spindle-associated protein gene in erythroid cells: essential role of NF-Y.

Nucleolar spindle-associated protein (NuSAP), a recently characterised microtubule-associated protein, appears to participate in cell cycle regulation. It has been demonstrated that NuSAP is expressed preferentially in the erythroid lineage in haematopoietic cells. To characterise its role in erythropoiesis, we examined the expression profile of the NuSAP gene. In fractionated murine erythroblasts, NuSAP mRNA was remarkably more abundant in the subset corresponding to immature erythroblasts (TER119(+)CD71(high)) than mature erythroblasts (TER119(+)CD71(low)), and it was significantly increased in TER119(+) cells from in vivo phlebotomised mice compared with control mice. Furthermore, during erythroid maturation of mouse erythroleukaemia (MEL) cells by dimethylsulfoxide, NuSAP mRNA was increased at 24-72 h. These results suggested that the NuSAP gene might contribute to the expansion of immature erythroblast pool. The regulatory mechanism of NuSAP gene was investigated using MEL cells. Sequence analysis revealed that NuSAP promoter has four CCAAT boxes, an Sp1 element, a GATA-like element, a CACCC element, a Myb element and lacks a TATA box. Promoter analyses demonstrated that duplicated CCAAT boxes located at -81/-85 and -30/-34 were essential for promoter activity. Furthermore, the promoter was trans-activated by NF-YA through these elements. These results suggest that NuSAP might play an important role in erythroid proliferation under the control of NF-Y.

5' Flanking Region↗
PubMed2006

NKT cells play a limited role in the neutrophilic inflammatory responses and host defense to pulmonary infection with Pseudomonas aeruginosa.

CD1d-restricted NKT cells are reported to play a critical role in the host defense to pulmonary infection with Pseudomonas aeruginosa. However, the contribution of a major subset expressing a Valpha14-Jalpha18 gene segment remains unclear. In the present study, we re-evaluated the role of NKT cells in the neutrophilic inflammatory responses and host defense to this infection using mice genetically lacking Jalpha18 or CD1d (Jalpha18KO or CD1dKO mice). These mice cleared the bacteria in lungs at a comparable level to wild-type (WT) mice. There was no significant difference in the local neutrophilic responses, as shown by neutrophil counts and synthesis of MIP-2 and TNF-alpha, in either KO mice from those in WT mice. Administration of alpha-galactosylceramide, a specific activator of Valpha14+ NKT cells, failed to promote the bacterial clearance and neutrophilic responses, although the same treatment increased the synthesis of IFN-gamma, suggesting the involvement of this cytokine downstream of NKT cells. In agreement against this notion, these responses were not further enhanced by administration of recombinant IFN-gamma in the infected Jalpha18KO mice. Our data indicate that NKT cells play a limited role in the development of neutrophilic inflammatory responses and host defense to pulmonary infection with P. aeruginosa.

Animals↗
PubMed2006

Antimicrobial susceptibility of respiratory tract pathogens in Japan during PROTEKT years 1-3 (1999-2002).

Data are presented on antimicrobial resistance among isolates of Streptococcus pneumoniae, Streptoco-ccus pyogenes, Haemophilus influenzae, and Moraxella catarrhalis collected in Japan during years 1-3 (1999-2002) of the Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin (PROTEKT) surveillance study. In addition to the standard panel of PROTEKT antimicrobial agents, eight other agents often used in Japan also were tested against these isolates. The majority (30%-55%) of S. pneumoniae and H. influenzae isolates were collected from patients with community-acquired pneumonia, whereas most (>70%) S. pyogenes isolates came from patients with tonsillitis/pharyngitis. Penicillin and macrolide resistance were high among isolates of S. pneumoniae, averaging 30.9%-44.5% and 77.2%-79.9%, respectively, across all centers over the 3 study years; the highest occurrences were reported among pediatric patients aged 0-2 years. The erm(B) genotype accounted for >50% of all erythromycin-resistant isolates each study year. S. pyogenes isolates were highly susceptible to most antimicrobial agents except the macrolides and tetracycline. beta-Lactamase production among H. influenzae isolates range was 8.5%-9.7% per annum. A total of 9 beta-lactamase-negative, ampicillin-resistant isolates were collected during the study. Almost all (>95%) M. catarrhalis isolates were beta-lactamase positive each year. Telithromycin was highly active against all pathogens examined in this study during all 3 years.

Adolescent↗
PubMed2006

Predictive value of N-acetylglucosaminyltransferase-V for superficial bladder cancer recurrence.

PURPOSE: GnT-V is an enzyme that catalyzes beta1-6 branching of N-acetylglucosamine on asparagine (N)-linked oligosaccharides of cell proteins. GnT-V expression has been closely related to malignant potentials in colon cancer, brain cancer and hepatocellular carcinoma. We determined whether GnT-V expression is predictive of superficial bladder cancer recurrence. MATERIALS AND METHODS: The cohort comprised 60 consecutive patients with first time superficial bladder cancer treated with transurethral resection. None of the patients received prophylactic intravesical therapy until recurrence. Paraffin embedded tumor specimens were immunohistochemically examined by the avidin-biotin peroxidase method using monoclonal antibody against GnT-V. Kaplan-Meier survival curves were generated to determine disease-free survival. Univariate and multivariate analyses were done to compare GnT-V expression to other clinical and pathological variables. RESULTS: GnT-V expression correlated inversely with tumor grade and stage. The positive incidence of GnT-V in G1 to G3 tumors was 7 of 9 (78%), 21 of 43 (49%) and 3 of 8 (38%), respectively. GnT-V was positive in 26 of 44 cases of pTa (60%) and in 5 of 16 of pT1 (31%) disease. The 31 patients with positive GnT-V expression had significantly higher disease-free survival than the 29 with negative GnT-V expression (log rank test p = 0.0034). Multivariate analysis revealed that patient age, pT, grade and negative GnT-V expression were independent predictors of recurrence (p = 0.015, 0.001, 0.019 and 0.011, respectively). CONCLUSIONS: Immunohistochemical detection of GnT-V is an independent predictor of superficial bladder cancer recurrence.

Aged↗
PubMed2006

Limited contribution of Toll-like receptor 2 and 4 to the host response to a fungal infectious pathogen, Cryptococcus neoformans.

The present study was designed to elucidate the role of Toll-like receptor (TLR) 2 and TLR4 in the host response to Cryptococcus neoformans. Both TLR2 knockout (KO) and TLR4KO mice produced interleukin-1beta (IL-1beta), IL-6, IL-12p40 and tumor necrosis factor-alpha (TNF-alpha) in sera and cleared this fungal pathogen from infected lungs at a comparable level to control littermate (LM) mice. Synthesis of these cytokines was not significantly different in the lungs of these KO mice and LM mice, although IL-1beta, IL-6 and IL-12p40 tended to be lower in TLR2KO, but not TLR4KO, mice than in controls. In addition, there was no significant reduction detected in the synthesis of IL-12 and TNF-alpha by bone marrow-derived dendritic cells from TLR2KO and TLR4KO mice upon stimulation with live yeast cells. Finally, HEK293 cells expressing either TLR2/dectin-1 or TLR4/MD2/CD14 did not respond to C. neoformans in the activation of nuclear factor kappa B (NFkappaB) detected by a luciferase assay. Our results suggest that TLR2 and TLR4 do not or only marginally contribute to the host and cellular response to this pathogen.

Animals↗
PubMed2006

Population pharmacokinetics of Arbekacin in patients infected with methicillin-resistant Staphylococcus aureus.

Arbekacin, a derivative of dibekacin, is an aminoglycoside developed and widely used in Japan for the treatment of patients infected with methicillin-resistant Staphylococcus aureus (MRSA). The population pharmacokinetics of arbekacin was investigated in the Japanese, using 353 patients infected with MRSA and 50 healthy or renally impaired volunteers. The age of the study population ranged from 8 to 95 years, and weight ranged from 10.8 to 107 kg. In total, 1,581 serum arbekacin concentrations were measured (primarily from routine patient care) and used to perform the present pharmacokinetic analysis. Drug concentration-time data were well described by a two-compartment open model. Factors influencing arbekacin pharmacokinetics were investigated using a nonlinear mixed-effect model analysis. The best-developed model showed that drug clearance (CL) was related to creatinine clearance (CL(CR)), age, and body weight (WT), as expressed by CL (liter/h) = 0.0319CL(CR) + (26.5/age) (CL(CR) < 80 ml/min) and CL (liter/h) = 0.0130 CL(CR) + 0.0342WT + (26.5/age) (CL(CR) >/= 80 ml/min). The volume of distribution for the central and peripheral compartments was different in healthy subjects and infected patients, and this difference was more pronounced among disease types. The elderly subjects (aged 80 years or over) exhibited, on average, a 19% greater volume for the central compartment. The volumes for the peripheral compartment were 50.6 liters in patients with pneumonia and 24.3 liters in patients with sepsis. The population pharmacokinetic parameters of arbekacin obtained here are useful for optimal use of this aminoglycoside in the treatment of MRSA-infected patients.

Adolescent↗
PubMed2006

Pharmacokinetic-pharmacodynamic relationship of arbekacin for treatment of patients infected with methicillin-resistant Staphylococcus aureus.

Arbekacin is widely used in Japan for the treatment of patients infected with methicillin-resistant Staphylococcus aureus (MRSA). In this study, we have determined the optimal concentration targets of arbekacin for both efficacy and safety. A pharmacokinetic-pharmacodynamic analysis was performed to relate exposure to the drug and clinical cure/improvement or nephrotoxicity. Since we have reported the population pharmacokinetic parameters for arbekacin in the preceding paper (Y. Tanigawara, R. Sato, K. Morita, M. Kaku, N. Aikawa, and K. Shimizu, Antimicrob. Agents Chemother. 50:3754-3762, 2006), individual exposure parameters, such as area under the concentration-time curve (AUC), peak concentration (C(max)), AUC/MIC, C(max)/MIC, and trough concentration (C(min)) were estimated by the Bayesian method. Logistic regression was used to describe the relationship between exposure to the drug and the probability of clinical cure/improvement or nephrotoxicity. For the clinical efficacy analysis, 174 patients confirmed to have an MRSA infection were evaluated. The C(max), C(min), and AUC of arbekacin were associated with the probability of clinical cure/improvement during monotherapy. It was shown that the probability of cure/improvement rose when the C(max) of arbekacin was increased, with an odds ratio of 6.7 for a change in C(max) from 7.9 to 12.5 microg/ml (P = 0.037). For the nephrotoxic risk analysis, 333 patients were included, regardless of whether a pathogen was identified. Logistic regression analysis revealed C(min) and AUC as risk factors of nephrotoxicity (P < 0.005). The estimated probabilities of arbekacin-induced nephrotoxicity were 2.5, 5.2, and 13.1% when the C(min) values were 1, 2, and 5 microg/ml, respectively. The present findings are useful for optimizing the individual dose of arbekacin for the treatment of MRSA-infected patients.

Adolescent↗
PubMed2006

Induction of erythroid-specific genes by overexpression of GATA-2 in K562 cells.

GATA transcription factors have been shown to play important roles in hematopoiesis. GATA-2 is expressed in stem and progenitor cells, and has been speculated to control the proliferation and maintain the immaturity of these cells. To examine whether the function of GATA-2 is changeable according to the differentiation stage, we established GATA-2 overexpressing subclones of K562, which is a leukemic cell line committed to the erythroid lineage. Via an increase in the GATA-2 expression level, the expression levels of erythroid-specific genes including alpha-, beta-, and gamma-globin were increased compared to control cells, while the expression level of GATA-1 was unchanged. Expression of the transferrin receptor was also increased in GATA-2 overexpressing K562 cells when examined by flow cytometry. In addition, the heme content of GATA-2 overexpressing K562 cells was more than 2 times higher than control cells. Chromatin immunoprecipitation analysis showed that GATA-2 protein binding to the GATA element in alpha-globin LCR was increased in GATA-2 overexpressing K562 cells. These findings suggest that GATA-2 could induce erythroid-specific genes without competition with GATA-1 when expressed in erythroid-committed cells, and thus further suggest that temporal and spatial regulation may be important for displaying specific functions of GATA-2.

Cell Differentiation↗
PubMed2006

Synergistic effect of arsenic trioxide and flt3 inhibition on cells with flt3 internal tandem duplication.

Flt3 internal tandem duplication (Flt3-ITD) is a prevalent mutation in acute myeloid leukemia (AML). Flt3-ITD constitutively activates various signaling pathways, including a mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway. Arsenic trioxide (ATO) and MEK inhibition were recently reported to interact synergistically to induce apoptosis in AML cells. In this study, we aimed to clarify whether ATO and Flt3 inhibition would be a more specific and efficient therapy for Flt3-ITD cells. We demonstrate that the combination of ATO and an Flt3 inhibitor, AG1296, profoundly inhibits the growth of Flt3-ITD cells and induces their apoptosis. We further revealed that this combined treatment potently inhibits the ERK activity that might be responsible for cell growth. Moreover, using the Chou-Talalay method, we observed a synergistic growth-inhibitory effect for ATO and AG1296 in Flt3-ITD cells (BaF3-Flt3-ITD, MV4-11, and PL-21 cells), but not in Flt3 wild-type cells (RS4-11 and NB4 cells), for almost all dose ranges tested. Our results provide an experimental basis for a specific and efficient therapy for Flt3-ITD cells that involves combined treatment with Flt3 inhibitors and ATO.

Antineoplastic Agents↗
PubMed2006

Increased expression of insulin-like growth factor i is associated with Ara-C resistance in leukemia.

Resistance to cytosine arabinoside (Ara-C) is a major problem in the treatment of patients with acute myeloid leukemia (AML). In order to investigate the mechanisms involved in Ara-C resistance, the gene expression profile of Ara-C-resistant K562 human myeloid leukemia cells (K562/AC cells) was compared to that of Ara-C-sensitive K562 cells (K562 cells) by using a cDNA microarray platform. Correspondence analysis demonstrated that insulin-like growth factor I (IGF-I) gene was upregulated in K562/AC cells. The biological significance of IGF-I overexpression was further examined in vitro. When K562 cells were incubated with IGF-I ligand, they were protected from apoptosis induced by Ara-C. In contrast, a significant inhibition of growth and increase of apoptosis of K562/AC cells were induced by IGF-I receptor neutralizing antibody, or suramin, a nonspecific growth factor antagonist. Moreover, from the analysis of 27 AML patients, we have shown that IGF-I expression levels are higher in patients at refractory stage, after Ara-C combined chemotherapy, than those in patients at diagnosis. These results suggest that the inhibition of IGF-I and its downstream pathway is a valuable therapeutic approach to overcome Ara-C resistance in AML.

Acute Disease↗
PubMed2006

[The relationship of autonomic functional disturbance and atherosclerosis in type 2 diabetes].

The aim of the study was to assess the relationship between the autonomic nerve disturbance and atherosclerotic changes in patients with type 2 diabetes. Aortic distensibility and max carotid intima-media thickness (Max IMT) were evaluated using brachial ankle pulse wave velocity (PWV) and high-resolution B-mode ultrasonography, respectively, in 135 patients (69 men, 66 women, 57 +/- 16 years) with type 2 diabetes. The autonomic neuropathy was evaluated using coefficient of variation of the RR interval (CV(R-R)) of electrocardiograms recorded at rest in a supine position. There was a significant negative correlation between CV(R-R)and Max IMT (r= -0.488, p< 0001). There were also significant negative correlations between CVR-(R a)nd the left and the right PWV(r=0.518, p<0.001; r=0.551, p<0.001, respectively). Patients with normal Max IMT, but decreased CVR-R, had a high PWV compared to patients with normal Max IMT and normal CVR-(R. )Therefore, decreased CVR-(R i)n type 2 diabetic patients may reflect atherosclerotic changes. Thus, the measurement of CVR-(R i)s a simple and quantitative test for assessing atherosclerotic as well as neuropathic complications in diabetic patients.

Atherosclerosis↗
PubMed2006

[Comparison between optical microscopic examination and phase contrast microscopic examination for diagnosing the origin of urinary bleeding].

PURPOSE: Phase contrast microscopy method is useful in the examination of urine sediment to differentiate glomerular(Gl) hematuria from non glomerular(nonGl) hematuria. In this study, we compared the diagnostic value of optical microscopy with that of phase contrast microscopy. METHOD: One hundred and sixty fresh urine samples of microscopic hematuria(5/HPF or more) from 118 patients with renal disease and 42 patients with urologic disease were analyzed. The erythrocytes referred to as Gl, are defined to have acanthocytes, target configuration, or finger ring shape, and a Gl cell/total erythrocyte ratio greater than 3% is defined as reliable marker for Gl bleeding. RESULT: Sensitivity and specificity of this criteria for Gl bleeding were 50.9% and 94.9% in acanthocytes, 69.6% and 89.1% in the target configuration, and 88.4% and 89.1% in the finger ring, respectively. As for the microscopic observation methods, the sensitivity and specificity of this criteria for GI bleeding were 88.1% and 81.0% with phase contrast microscopy, 74.6% and 90.9% with optical microscopy with no dyeing, and 74.6% and 88.6% with optical microscopy with dyeing, respectively. CONCLUSION: GI and nonGl hematuria were correctly diagnosed by counting the urinary Gl cells not only by phase contrast microscopy, but also by optical microscopy. This method seems to have important clinical usefulness by offering information on urinary bleeding.

Adolescent↗
PubMed2006

[Role of medical technologists in the infection control team].

The infection control team (ICT) plays important roles in many different aspects of infection control. They include (1) surveillance for hospital-acquired infection, (2) developing the infection control manual, (3) checking that the manual is followed correctly, (4) giving information about the isolation of microorganisms in the hospital, (5) educating and instructing medical staff, etc. Many data have been accumulated on a database in the microbiology laboratory. Bacterial samples are also examined in the microbiological laboratory therefore medical technologists will be the first to notice hospital-acquired infection. Offering prompt information, obtained by surveillance or routine work, greatly contributes to infection control. Furthermore, a 24hr system for the microbiological laboratory may prevent occupational infection of health care workers. The role of the medical technologist in ICT is thus important. To prevent outbreaks of infection, the regional network is also important for the collection of information about the pathogen and the susceptibility of antimicrobial agents in the region. The medical technologist should participate in and communicate with this network. As mentioned above, the inclusion of medical technologists in infection control practice is essential. To participate in the ICT, medical technologists need to have communication skills, and be recognized by other team members as an essential member.

Bacteria↗
PubMed2006

[Infection control measures in surgical wards and operating theaters].

A variety of infection control measures are practiced to decrease the risk of transmission of pathogens. Standard precautions are thought to be the most effective against healthcare-associated infections. However, compliance with standard precautions is not sufficiently high in Japanese hospitals. Frequent handwashing is an important measure to reduce the risks of transmitting infectious organisms from one person to another, although it is not easy to maintain high compliance in healthcare settings. This problem has not been fundamentally resolved, although infection control practitioners have addressed this problem for more than 100 years. It is recommended that healthcare workers wear personal protective equipment, such as masks, gowns, gloves, goggles, and face shields, to provide barrier protection. Environmental consideration of operation rooms must be performed in order to decrease surgical site infections. Operating theaters should be cleaned routinely, if possible using a wet vacuum. Clean air should be supplied through high-efficiency particulate air filters and positive pressure maintained. Surgeons should be aware that they are an important potential source of surgical site infection.

Humans↗
PubMed2006

[Significance of urine dipstick test for occult blood in patients with diabetes mellitus].

OBJECTIVE: Hematuria is the usual urinary finding in patients with diabetic nephropathy. In this study, prevalence and significance of microhematuria in patients with diabetes mellitus were investigated. MATERIAL AND METHODS: Five hundred and forty-two samples from outpatients, who consulted the Department of Diabetes and Metabolism, were categorized into 4 groups according to the results of the urine dipstick test. Group I :258 samples, urinary protein(u-P) 1+ and occult blood (OB) negative, group II: 95 samples: u-P 1+, OB 1+ approximately 3+, group III: 89 samples: u-P 2+ approximately 3+, OB negative, group IV 100 samples u-P 2+ approximately 3+, OB 1+ approximately 3+. RESULTS: Serum concentrations of creatinine and highly sensitive CRP were both significantly higher in group II than in group I . Those parameters were also significantly higher in group IV than in group III. CONCLUSIONS: These results indicate that a positive dipstick test for OB may occur in many patients with diabetes mellitus and suggest the progress of renal damage.

Creatinine↗