Search PubMed⌕ Search

Biomedical subjects

Satoshi Kimura

Publications and source records attributed to Satoshi Kimura.

At least 19 recordsLinked to original sources

Successful vancomycin desensitization with a combination of rapid and slow infusion methods.

Vancomycin, an antibiotic to which methicillin-resistant Staphylococcus aureus (MRSA) is sensitive, frequently induces hypersensitivity reactions. Lowering the vancomycin infusion rate and/or premedicating with antihistamine effectively reduce hypersensitivity in most cases. However, vancomycin desensitization is sometimes the only way to ensure safe use. Two types of desensitization protocols have been reported, and these utilize different infusion intervals; rapid desensitization and slow desensitization. We herein report a case of vancomycin hypersensitivity with methicillin-resistant Staphylococcus aureus infection. A combination of the two desensitization protocols, rapid desensitization followed by slow desensitization, effectively inhibited the hypersensitivity reaction during vancomycin infusion, and methicillin-resistant Staphylococcus aureus was successfully eradicated.

Adult↗

Decrease in Epstein-Barr virus-positive AIDS-related lymphoma in the era of highly active antiretroviral therapy.

Recent introduction of highly active antiretroviral therapy (HAART) is reported to have reduced the incidence of lymphoma among HIV-infected individuals. A clinicopathological study was performed on 86 AIDS-related lymphoma patients who were treated in Tokyo area from 1987 to 2005. The incidence of lymphoma detected by autopsy was 27% (53 cases/198 autopsies). Diffuse large B cell lymphoma was the most predominant histological subtype throughout the period (78%). Burkitt's lymphoma (BL) increased from 2% in the pre-HAART era (before end-1997) to 13% in the HAART era, whereas incidence of BL did not vary between HAART users and non-users. Epstein-Barr virus (EBV)-positive lymphoma decreased from 88% in the pre-HAART era to 58% in the HAART era, but did not differ significantly between HAART users (73%) and non-users (74%). Nodal involvement of lymphoma increased from 14% in the pre-HAART era to 50% in the HAART era; however, central nervous system involvement decreased from 62 to 38%. Kaposi's sarcoma-associated herpesvirus infection was rare (4%) among all cases. These data suggest that HAART might play a partial role in these changes, and the alteration in immunological backgrounds, such as EBV prevalence, is suggested as another leading cause of these changes in Japanese AIDS-related lymphoma.

Adolescent↗

Cooperative contribution of gag substitutions to nelfinavir-dependent enhancement of precursor cleavage and replication of human immunodeficiency virus type-1.

We previously described a clinical human immunodeficiency virus type-1 (HIV-1) isolate, CL-4, which showed nelfinavir (NFV)-dependent enhancement of replication (Matsuoka-Aizawa, S., Sato, H., Hachiya, A., Tsuchiya, K., Takebe, Y., Gatanaga, H., Kimura, S., Oka, S, 2003. Isolation and molecular characterization of a nelfinavir (NFV)-resistant human immunodeficiency virus type 1 that exhibits NFV-dependent enhancement of replication. J. Virol. 77, 318-327.). To identify the responsible region(s) of HIV-1 proteins for such replication enhancement, we constructed a panel of recombinant HIV-1 clones harboring portions of the Gag and protease of CL-4 and analyzed their replication capabilities and Gag processing patterns. Our data suggested that the substitutions in the matrix and N-terminal half of capsid of CL-4 were indispensable for the NFV-dependent enhancement of replication and that NFV facilitated the cleavage between the matrix and capsid of the Gag precursor harboring these substitutions. The substitutions in C-terminal half of capsid rather decreased the cleavability of Gag precursor and NFV counteracted such negative impact. Efficient replication enhancement with NFV can be observed only in the presence of the substitutions in entire Gag and protease of CL-4.

Amino Acid Sequence↗

Emergence of multidrug-resistant Corynebacterium striatum as a nosocomial pathogen in long-term hospitalized patients with underlying diseases.

During a 53-month period (March 1994 to August 1998), 48 Corynebacterium striatum isolates recovered from clinical specimens were characterized. The organisms were identified by both phenotypic characteristics and 16S rRNA gene sequence analysis. Thirty-six (75%) were isolated from sputum/bronchial aspirates, 10 (21%) from wound exudates/pus, 1 (2%) from vaginal discharge, and 1 (2%) from an otorrheic specimen. All 48 patients had been hospitalized for treatment of an underlying disease and had received antibiotics previously. The C. striatum isolates were considered pathogenic based on their abundance within polymorphonuclear neutrophils and their dominant growth in culture. Sensitivities of isolates to 11 antibiotics were determined by broth microdilution. MIC90 values of the isolates were 1 microg/mL for vancomycin, 16 microg/mL for penicillin and ampicillin, 32 microg/mL for minocycline, and > or = 32 microg/mL for cephalosporins, imipenem, ofloxacin, and macrolides. Restriction fragment-length polymorphism analysis with pulsed-field gel electrophoresis was used to determine the clonal identity. The pulse-field gel electrophoresis profiles revealed 14 distinct patterns with 20 subtypes. The isolates for the nosocomial outbreaks of C. striatum included 3 types (A, D, and E) with 4 subtypes (A1, A2, D2, and E). All 4 genotypes had broad-spectrum resistance to antimicrobial agents. Furthermore, type E strain isolated from 3 patients in the same ward was sensitive only to vancomycin. We conclude that C. striatum should be considered an emerging multidrug-resistant nosocomial pathogen in patients hospitalized for a prolonged period and/or in immunocompromised patients with such underlying conditions as cerebrovascular disease, pulmonary disease, diabetes, or malignancy.

Anti-Bacterial Agents↗

Simultaneous determination of six HIV protease inhibitors (amprenavir, indinavir, lopinavir, nelfinavir, ritonavir and saquinavir), the active metabolite of nelfinavir (M8) and non-nucleoside reverse transcriptase inhibitor (efavirenz) in human plasma by high-performance liquid chromatography.

We report the development of a simple, economical and reliable chromatographic method for the simultaneous determination of six HIV protease inhibitors (PIs; amprenavir, indinavir, lopinavir, nelfinavir, ritonavir and saquinavir), the active metabolite of nelfinavir (M8) and the non-nucleoside reverse transcriptase inhibitor (NNRTI; efavirenz) in human plasma. After extraction from plasma with an ethyl acetate-acetonitrile mixture, the analytes were separated on a phenyl column with a gradient of acetonitrile and phosphate solutions, and detected at three ultraviolet wavelengths. Calibration curves were linear over the range 0.025-15 microg/mL for saquinavir and 0.05-15 microg/mL for the other analytes. The accuracies ranged from -6.9% to +7.6%, and the intra-assay and inter-assay precisions were <9.2 and <11.8%, respectively. Our method, covering most of the PIs and NNRTIs currently used, facilitates ready therapeutic drug monitoring in hospital laboratories.

Alkynes↗

Differential effects of apolipoprotein E isoforms on lipolysis of very low-density lipoprotein triglycerides.

Apolipoprotein (apo) E plays a key role in lipoprotein metabolism and has been proposed to modulate triglyceride (TG) lipolysis. However, no systematic investigation on lipolysis using all 3 isoforms of apoE has been performed. To clarify the role of common human apoE isoforms in the lipolysis of very low-density lipoprotein (VLDL) TGs, we overexpressed human apoE isoforms in apoE and low-density lipoprotein receptor-deficient mice using adenoviral-mediated gene transfer and used VLDL particles obtained from these mice for in vitro lipolysis assay. Overexpression of apoE, regardless of its isoforms, increased the TG content of VLDL in mice in vivo. In vitro analysis of the effect of apoE on lipolysis revealed that irrespective of its isoforms, apoE did inhibit TG lipolysis at every concentration of apoE examined, and this inhibitory effect became more pronounced as the apoE content of VLDL increased. No difference was observed in TG lipolysis activity among isoforms at low apoE/TG ratio; however, intermediate ratios of apoE/TG, which reflect physiologic VLDL apoE/TG ratios, demonstrated a significantly greater level of lipolysis inhibition in apoE2, but less so in apoE4 compared with other isoforms. This differential effect by apoE isoforms on lipolysis was attenuated at higher apoE/TG ratios; nevertheless, apoE2 still inhibited lipolysis significantly more than did apoE4. Enrichment of VLDL with apoE decreased both the apoC contents and apoC-II/C-III ratios of VLDL, contributing, at least in part, to the inhibitory function of apoE on lipolysis. The present study clarifies the differential lipolysis-modulating effect of apoE isoforms, which would help explain the difference in pre- and postprandial TG levels among humans carrying different apoE isoforms.

Adenoviridae↗

[The efficacy of safety winged steel needles on needlestick injuries].

Safety winged steel needles were introduced at the University of Tokyo Hospital in January 2001. We studied their effect in needlestick injuries. A total of 952 'needlestick and sharp-object injuries were reported. From January 1999 to December 2004, Cases of injury with winged steel needles decreased dramatically soon after safety devices were introduced, from 19.8% in Apr.-Dec.2000 to 6.7% in 2001 and 5.5% in 2002 (p < .01). They began to increase, however, in July 2002, decreased again after medical staff members mere given lectures and notices by e-mail. Due to the introduction of safety devices, cases classified as a "while recapping a used needle" and "when puncturing rubber stoppers" decreased. Among 17 injuries with safety winged steel needles, the most common cases were "safety mechanism not activated". We estimated that 76.5% of cases with safety winged steel needles could be prevented if they were used properly. In conclusion, the introduction of safety winged steel needles effectively reduced cases of injury with such needles. It is thus important to regularly remind hospital staff of safety device techniques and information reduce the such injuries.

Equipment Design↗

Difference of progression to AIDS according to CD4 cell count, plasma HIV RNA level and the use of antiretroviral therapy among HIV patients infected through blood products in japan.

BACKGROUND: It is important to examine progression to acquired immunodeficiency syndrome (AIDS) or death and its predictors among human immunodeficiency virus (HIV) infected persons before and after the introduction of the highly active antiretroviral therapy (HAART) available in Japan since 1997. METHODS: The data used were from a survey of persons with HIV infected through blood coagulation factor products in Japan. Progression to AIDS or death during two periods, between January 1994 and March 1997, and between April 1997 and March 2002, were observed. RESULTS: The AIDS-free proportion after 3 years was 74% among 417 participants for the earlier period and 94% among 605 participants in the later one. The hazard ratio of low CD4 cell count (less than 200 cells/microL) was 50.8 for the earlier period and 4.7 for the later one compared with that of 500 cells/microL or more. After adjustment by plasma HIV RNA levels and use of antiretroviral therapy, the hazard ratios of the low CD4 cell count for the later period were still significant. CONCLUSION: The AIDS-free proportion among people with HIV infected through blood products in Japan largely increased after the introduction of HAART. The CD4 cell count remains an important predictor of future progression, but its importance might be less because of HAART.

Acquired Immunodeficiency Syndrome↗

[The positivity of specific IgE to salmon roe and cod roe in outpatients].

PURPOSE: To clarify the positivity of specific IgE to salmon and cod roe in outpatients. METHODS: Specific IgE were assayed using CAP RAST system in 91 pediatric outpatients. They were 47 males and 44 females, including 22 allergic, 29 infectious, 10 neurological, 8 gastrointestinal, 7 urological, 6 hematologic, 3 metabolic disease and 6 other disorders. For control, 30 sera from healthy normal adult volunteers were assayed. Additionally, sera from 653 allergic patients were also collected in our laboratory. Specific IgEs against salmon and cod meat were also assayed simultaneously. RESULTS: In 91 pediatric patients, two children were salmon roe positive and one child was cod roe positive. Three children scored class 1, borderline positive in salmon roe, and one child scored class 1 in cod roe. Other children were negative in all allergens. No positive sera were found in normal adult volunteers. Among 653 specimens in our laboratory, the positivity of specific IgE to salmon and cod roe were 25%, and 9%, respectively. Infants younger than two years old had higher ratio than older children. There was a significant correlation (r = 0.676) between the titers of IgE to salmon and cod roe. On the other hand, the titers of IgE to their meats correlated less than those to their roes. Our results support previous reports that fish roe from different species have common antigen apart from those of fish meat. CONCLUSION: Positive ratio of salmon and cod roe specific IgE were 2.2 and 1.1% in pediatric outpatients.

Adult↗

Mutations other than 103N in human immunodeficiency virus type 1 reverse transcriptase (RT) emerge from K103R polymorphism under non-nucleoside RT inhibitor pressure.

K103N mutation in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) confers high-level resistance against non-nucleoside RT inhibitors (NNRTIs) and it easily occurs partly because it arises by a single nucleotide substitution from wild-type K103. There are polymorphisms at codon 103 of HIV-1 RT. We found K103R polymorphic mutation in 3.3% of treatment-naive HIV-1-infected patients. R103N does not seem to occur as easily as K103N because R103N requires two nucleotide substitutions. To induce NNRTI resistance-associated mutations, HIV-1K103R was propagated in the presence of increasing concentrations of efavirez (EFV) or nevirapine (NVP). V179D emerged in all three EFV cultures and in two of four NVP cultures. R103G emerged by a single nucleotide substitution in one of three EFV cultures. R103N did not emerge in any of 7 NNRTI cultures. Analysis of recombinant HIV-1s showed that HIV-1K103R/V179D was significantly resistant and HIV-1K103G was moderately resistant against EFV and NVP.

Amino Acid Substitution↗

Adenovirus-mediated gene transfer and lipoprotein-mediated protein delivery of plasma PAF-AH ameliorates proteinuria in rat model of glomerulosclerosis.

Oxidative stress has been proposed to play a crucial role in glomerulosclerosis, although its in vivo demonstration has proved taxing given the difficulty of inducing gene expression in specific renal cells. In this study, we examined whether the liver-directed expression of plasma platelet-activating factor acetylhydrolase (PAF-AH) would affect the glomerular pathophysiology in Imai rats, an animal model for glomerulosclerosis. Adenovirus-mediated liver-directed gene delivery of human PAF-AH resulted in a significant increase in plasma PAF-AH activity, which was detected almost exclusively on HDL. Histological examination of rats overexpressing PAF-AH showed not only the deposition of PAF-AH in mesangial cells, but also a reduction in hydroxynonenal and matrix protein content in the glomeruli. In situ hybridization analysis was negative for human PAF-AH mRNA in the kidney, while injection of HDL abundant in PAF-AH resulted in the deposition of PAF-AH in mesangial cells. Urine protein levels did not increase in rats overexpressing PAF-AH, while those of control rats increased significantly with age. This study provides direct evidence of the in vivo role of an enzyme that degrades lipid peroxides during the progression of glomerulosclerosis. Adenovirus-mediated extrarenal gene expression and lipoprotein-mediated glomeruli-targeted protein delivery promise to be a novel therapeutic approach to glomerulosclerosis.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Ischemia-modified albumin levels in cord blood: a case-control study in uncomplicated and complicated deliveries.

BACKGROUND: In the past few years ischemia modified albumin (IMA) has emerged as a new biomarker of ischemia in the area of monitoring acute coronary syndromes. We hypothesized that reduced blood flow, such as that resulting from vascular compression in complicated labors or placental ischemia, may increase IMA. IMA level in cord blood could then serve as an indicator of fetal hypoxia and fetal tissue ischemia and serve as a biomarker of the severity of these conditions. METHODS: We performed a case-control study with 26 newborns (12 normal term deliveries, Apgar 8-9; and 14 complicated labors or pre-term deliveries, Apgar 5-8). Complications were: prematurity (3), fetal distress (6), premature rupture of membranes (6), intrauterine growth retardation (3), pre-eclampsia (1). We also studied 30 healthy adults. IMA was measured in serum from cord blood (or venous blood for adults) by the decrease in cobalt 2+ binding. RESULTS: IMA levels in neonates from non-complicated deliveries are significantly higher (45%, p < 0.005) than those of an adult control population, suggesting that IMA may increase as a consequence of labor. This increased IMA in neonates could not be accounted for by the changes in albumin concentration. It is conceivable that a transient increase in IMA reflects, in part, transient localized tissue ischemia due to the external forces exerted on the fetus during the mechanism of labor. IMA levels in cord blood from neonates from complicated deliveries are 50% higher than in neonates from uneventful deliveries (p < 0.05) while their albumin values are not significantly different (32 +/- 3 vs. 33 +/- 2 g/l). Moreover, IMA seems to be responsive to hypoxic fetal distress, showing values more than 300% higher in cases of severe fetal hypoxia (Apgar 5 n = 2: 2.19 +/- 0.01 AU vs. 0.64 +/- 0.24 for controls). IMA values did not correlate significantly with either lipoperoxides or CRP levels. CONCLUSIONS: This is the initial reporting of IMA levels in cord blood from normal deliveries compared to healthy adult ranges and neonates from complicated deliveries. Cord blood IMA levels may be an indicator of fetal ischemia and/or hypoxia. This test could become an additional biomarker to be used in conjunction with other markers and/or clinical scores aimed at determining risk of neurological complications of fetal distress.

Adult↗

Efficacy and immunologic responses to influenza vaccine in HIV-1-infected patients.

Influenza vaccine is recommended for HIV-1-infected patients. The present prospective study was conducted to evaluate the clinical efficacy and immunologic responses to the vaccine. From November 1 to December 27, 2002, 262 HIV-1-infected patients received a trivalent influenza subunit vaccine, whereas 66 did not. Influenza illness occurred in 16 vaccinated and 14 nonvaccinated patients (incidence = 6.1% [95% confidence interval (CI): 4%-10%] in vaccinated vs. 21.2% [CI: 13%-35%] in nonvaccinated persons, P < 0.001; relative risk = 0.29 [CI: 0.14-0.55]). Influenza vaccine provided clinically effective protection against influenza illness in HIV-1-infected patients. In baseline antibody-negative patients, anti-H1 and anti-H3 antibody responses to the vaccination were significant in those patients with a CD4 count >200 cells/muL compared with those with a CD4 count <200 cells/muL (P < 0.05). In contrast, in baseline antibody-positive patients, good antibody responses were observed irrespective of CD4 counts, like the healthy controls. Based on these results, annual vaccination is recommended. Specific CD4 responses correlated with HIV-1 viral load (VL), especially in patients treated with highly active antiretroviral therapy (HAART) compared with those without HAART (P < 0.01), although the clinical efficacy did not correlate with HIV-1 VL. HAART may enhance the immunologic efficacy of influenza vaccine.

Acquired Immunodeficiency Syndrome↗

Modified Dynabeads method for enumerating CD4+ T-lymphocyte count for widespread use in resource-limited situations.

The Dynabeads method showed the potential for enumerating CD4 T lymphocytes (CD4 count) in HIV-1-infected individuals. The large volume of Dynabeads required for 1 sample and complex procedure made the method expensive and not easy for use, however. To decrease the cost and simplify the procedure, we reduced the volume of the Dynabeads, added wash times, and skipped over the staining step so as to count the CD4 cells directly under an optical microscope. The CD4 count of 246 blood samples using our modified Dynabeads method (DynabeadsCD4) showed a significant correlation with that obtained by flow cytometry (FlowcytoCD4) (r = 0.91 [P < 0.0001]; slope = 1.03, intercept = -16). The sensitivity and specificity for a CD4 count less than 200 cells/microL were 79% and 94%, and for a CD4 count less than 350 cells/microL, the sensitivity and specificity were 95% and 88%, respectively. The positive and negative predictive values for a CD4 count less than 350 cells/microL were 97% and 83%, respectively. The systematic error was 8 cells/microL (95% confidence interval [CI]: 0.4-16). The cost of Dynabeads for 1 sample was less than $1.00; thus, the estimated cost per DynabeadsCD4 test is less than $3.00, including the cost of other disposable materials. Our modified method is simple, economic, and accurate enough to monitor antiretroviral therapy in resource-limited situations.

Adult↗