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Biomedical subjects

Masaru Nasu

Publications and source records attributed to Masaru Nasu.

At least 19 recordsLinked to original sources
PubMed2004

Effect of Helicobacter pylori eradication on platelet recovery in patients with chronic idiopathic thrombocytopenic purpura.

BACKGROUND: A relationship between Helicobacter pylori infection and idiopathic thrombocytopenic purpura (ITP) has previously been reported. We determined the prevalence of H pylori infection in Japanese patients with chronic ITP and the effect of its eradication on platelet count. METHODS: The study population comprised 53 Japanese adults with chronic ITP and a platelet count of less than 100 x 10(3)/ micro L. A (13)C-urea breath test was performed to determine H pylori infection status. Those patients who were H pylori positive gave written informed consent and received eradication therapy. The effect of H pylori eradication on platelet count was evaluated up to 6 months after therapy. Clinical parameters were compared between responders to the therapy (increase in platelet count) and nonresponders, as well as between H pylori-positive and -negative patients. RESULTS: Of the 53 patients with chronic ITP in the study, 39 (74%) were H pylori positive. Of the 32 infected patients who received treatment, H pylori was successfully eradicated in 27 patients (84%). In 10 (37%) of these patients, this resulted in a favorable platelet response. A partial response was seen in 5 additional patients (19%). A significant (P<.001) increase in platelet count was demonstrated in patients in whom H pylori was successfully eradicated but not in patients who were unsuccessfully treated or in untreated patients. Current corticosteroid therapy was reported more often in nonresponders than in responders. CONCLUSION: Eradication of H pylori may prove effective in increasing platelet count in H pylori-positive patients with chronic ITP.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2004

The transcription factor CCAAT-binding factor CBF/NF-Y and two repressors regulate the core promoter of the human pro-alpha3(V) collagen gene (COL5A3).

To elucidate the mechanisms underlining alpha3(V) collagen chain expression, we performed an initial analysis of the structure and function of the core promoter of the human COL5A3 gene. The core promoter, which lacks a typical TATA motif and has a high GC content, was defined within the -129 bp immediately upstream from the major transcription start site by transient transfection experiments. In this region, we identified four DNA-protein complexes, named A, B, C, and D, by a combination of DNase I footprinting and electrophoretic mobility shift assays. Electrophoretic mobility shift assays using mutant oligonucleotide revealed that the complexes A, B, C, and D bind to -122 to -117, the -101 to -96, the -83 to -78, and the -68 to -57 bp, respectively. The competition assays using consensus oligonucleotides and supershift assays with specific antibodies showed that complex A consists of CBF/NF-Y. In a chromatin immunoprecipitation assay, CBF/NF-Y protein directly bound to this region, in vivo. Functional analysis showed that CBF/NF-Y activated the gene, whereas the proteins of complexes B and C repressed its activity. Furthermore, overexpression of a mutant form of the CBF-B/NF-YA subunit, which forms CBF/NF-Y with CBF-A/NF-YB and CBF-C/NF-YC subunits, inhibited promoter activity.

Amino Acid Motifs↗
PubMed2004

Association of peripheral mononuclear cells containing Chlamydia pneumoniae DNA with acute coronary syndrome and stable coronary artery disease in Japanese subjects.

To clarify the association of Chlamydia pneumoniae DNA in peripheral blood mononuclear cells (PBMCs) with acute coronary syndrome (ACS) and stable coronary artery disease (CAD) in Japanese adults, touchdown-nested polymerase chain reaction was used to detect the presence of C. pneumoniae DNA. The prevalence of C. pneumoniae DNA in PBMCs was similar in a comparison of 88 patients (52.3%) with ACS, 164 patients (50.0%) with stable CAD, and 88 control subjects (50.0%). Temporal changes in the prevalence of C. pneumoniae DNA in PBMCs were also assessed every 3 months during a 1-year period (n=59). The prevalence was significantly higher in the first 3-month period (January through March) than in any of the other 3-month periods. In conclusion, the prevalence of C. pneumoniae DNA in PBMCs in patients with ACS or stable CAD was comparable to that in control populations. Furthermore, the presence of circulating C. pneumoniae was strongly associated with seasonal variability.

Aged↗
PubMed2004

Antimicrobial susceptibilities and analysis of genes related to penicillin or macrolide resistance in Streptococcus pneumoniae.

One hundred and seventy-seven strains of Streptococcus pneumoniae derived from respiratory specimens between 1987 and 2001 were evaluated for their antimicrobial susceptibilities and distribution of genes related to penicillin and macrolide resistance. Resistance rates tended to be higher for the 1996-2001 isolates than for the 1987-1995 isolates for all beta-lactams tested. For benzylpenicillin the MIC(90) value of the isolates derived between 1996 and 2001 was 1.56 mg/L, while that of strains isolated between 1987 and 1990 was 0.05 mg/L. Furthermore, the number of strains susceptible to macrolides also decreased, but only two strains isolated in 1993 were resistant to levofloxacin of the 177 S. pneumoniae strains tested. When of genes relating to penicillin resistance were analysed using PCR with primers specific to susceptible alleles, although more than 50% of strains from 1987 to 1990 and 1991 to 1995 revealed no mutations in the pbp 1a, 2x and 2b genes, only 30.0% of strains derived between 1996 and 2001 showed no mutations in the pbp gene. Strains having mutations in all three pbp genes (1a, 2x and 2b) by the PCR method increased from only 2.2% in the 1987-1990 derived strains to 27.5% in the 1996-2001 strains. Furthermore, 64.1 and 60.0% of the isolates from 1987 to 1990 and 1991 to 1995, respectively, did not possess either the mefA or ermB by PCR analysis. Conversely, 75.0% of isolates from 1996 to 2001 possessed mefA and/or ermB. These genetic changes may explain the increase in the number of penicillin and macrolide resistant strains. We believe that it is important to evaluate changes in MIC as well as genetic mutations in order to select the most appropriate therapy for S. pneumoniae infections.

Anti-Bacterial Agents↗
PubMed2004

Clarithromycin and azithromycin induce apoptosis of activated lymphocytes via down-regulation of Bcl-xL.

To evaluate the anti-inflammatory action of macrolide antibiotics, we examined whether macrolide antibiotics could induce apoptosis of activated lymphocytes. The proportion of apoptotic cells was augmented by clarithromycin (CLR) and azithromycin (AZM) compared with control. There was no significant difference in Fas and Fas-ligand expression between the control and macrolide-treated groups. CLR and AZM inhibited the expression of Bcl-xL compared with that of control. Our results suggest that CLR and AZM enhance apoptosis of activated lymphocytes by down-regulation of Bcl-xL.

Adult↗
PubMed2004

Micro-broth dilution method with air-dried microplate for determining MICs of clarithromycin and amoxycillin for Helicobacter pylori isolates.

MICs of clarithromycin and amoxycillin for 253 isolates of Helicobacter pylori were measured by an air-dried microplate method and compared with the results obtained by the agar plate dilution method. The air-dried microplate method is performed by coating each well of a 96-well microplate with the test antibiotic and air-drying it. There were no marked differences between the air-dried microplate method and agar plate dilution methods in the MIC(50) and MIC(90) values or MIC ranges of clarithromycin obtained for the 253 isolates of H. pylori. More specifically, the MICs of clarithromycin for 114 (45.1 %) of the 253 isolates were the same by the air-dried microplate method as the agar plate dilution method, and the differences in the MICs of clarithromycin for a further 114 isolates (45.1 %) varied within one twofold dilution. The MICs of amoxycillin by the former method were in close agreement with the MICs obtained by the latter method: MICs of amoxycillin for 199 (78.7 %) of the 253 isolates were the same by both methods, and the differences in the MICs of amoxycillin for 42 isolates (16.6 %) varied within one twofold dilution. These results indicate that the air-dried microplate method is a useful method for determination of MICs, because the results obtained were in close agreement with those obtained by the standard agar plate dilution method. The air-dried microplate method is, therefore, a convenient and reliable method for determining the MICs of clarithromycin and amoxycillin for H. pylori isolates.

Amoxicillin↗
PubMed2004

Spontaneous remission of Epstein-Barr virus-negative non-Hodgkin's lymphoma after withdrawal of cyclosporine in a patient with refractory anemia.

A 70-year-old man presented with pancytopenia in August 2000, and the results of a bone marrow examination performed in January 2001 confirmed the diagnosis of refractory anemia. He was treated with cyclosporine (CsA) at 3.3 mg/kg per day, and the pancytopenia improved. The patient complained of epigastralgia 21 months later, and a gastric endoscopic examination showed an ulcer with a cleaved bank. A biopsy revealed diffuse large B-cell lymphoma. In situ hybridization analysis detected no Epstein-Barr virus (EBV) in the lymphoma. CsA treatment was discontinued, and a gastrectomy was performed 31 days later. A detailed histologic examination revealed no infiltration of abnormal B-cells in the resected stomach. Although EBV-positive lymphoma is a known complication of immunosuppressive therapy, no causal association between immunosuppressants and EBV-negative lymphoma has been established. The spontaneous remission observed after the withdrawal of CsA treatment suggests that immunosuppressive therapy can be a pathogenic factor in a subset of EBV-negative lymphomas.

Aged↗
PubMed2004

Response to cyclosporine therapy in patients with myelodysplastic syndrome: a clinical study of 12 cases and literature review.

Cyclosporine (CyA) was administered to 12 patients with myelodysplastic syndrome (MDS), and a response (major erythroid response, according to International Working Group criteria) was observed in 7 patients (58.3%). The median duration of response was 18 months (range, 3-22 months). Two patients are still responding and continuing to take CyA. Three patients stopped because of malignancy complications. To identify variables associated with responsiveness to CyA therapy, we analyzed the treatments of 72 MDS patients, comprising the 12 new patients and 60 patients previously described in the literature. Responses were observed in 44 of the 72 patients (61.1%). Univariate analyses revealed that higher daily dose of CyA (P for trend test, .007) and shorter disease duration (median, 5 months versus 17.5 months, P = .04) were factors significantly associated with response. No significant associations were observed between response and bone marrow features such as erythroid hypoplasia or hypoplastic marrow. Multivariate analysis also demonstrated that high CyA dose (>5 mg/kg per day) was significantly associated with response (P = .02). The present study showed that CyA therapy is useful for MDS patients with any marrow cellularity. Shorter disease duration is a pretreatment variable correlated with response, and a higher CyA dose results in a higher response rate.

Adolescent↗
PubMed2004

[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (2002)].

From October 2002 to September 2003, we collected the specimen from 476 patients with lower respiratory tract infections in 16 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various antibacterial agents and patients' characteristics. Of 584 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in inflammation, 578 strains were examined. The breakdown of the isolated bacteria were: Staphylococcus aureus 77, Streptococcus pneumoniae 103, Haemophilus influenzae 95, Pseudomonas aeruginosa (non-mucoid) 61, P. aeruginosa (mucoid) 23, Klebsiella pneumoniae 36, Moraxella subgenus Branhamella catarrhalis 29, etc. Of 77 S. aureus strains, those with 2 microg/ml or less of MIC of oxacillin (MPIPC) [methicillin-susceptible S. aureus: MSSA] was 34 strains (44.2%) and those with 4 microg/ml or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) was 43 strains (55.8%). Against MSSA, imipenem (IPM) and minocycline (MINO) had the most potent antibacterial activity and inhibited the growth of all the strains at 0.25 microg/ml. Although clindamycin (CLDM) and aminoglycosides also had the potent activity, the resistant strains against those agents were detected. Cefotiam (CTM) inhibited the growth of all the strains at 1 microg/ml without the low sensitive strains. Against MRSA, vancomycin (VCM) showed the most potent activity and inhibited the growth of all the strains at 2 microg/ml. Arbekacin (ABK) also showed the relatively potent activity and inhibited the growth of all the strains at 4 microg/ml. Carbapenems showed the most potent activities against S. pneumoniae and inhibited the growth of all the strains at 0.25-0.5 microg/ml. Cefozopran (CZOP) also had a preferable activity (MIC90: 1 microg/ml) and inhibited the growth of all the strains at 2 microg/ml. In contrast, the resistant strains for cefaclor (CCL), erythromycin (EM), CLDM, and tetracycline (TC) were detected in 50.5%, 76.7%, 50.5%, and 80.6% of all the strains, respectively. Against H. influenzae, LVFX showed the most potent activity and inhibited the growth of 92 of all the strains (96.8%) at 0.063 microg/ml. Tobramycin (TOB) showed the most potent activity against P. aeruginosa (both mucoid and non-mucoid) and inhibited the growth of all the strains at 2 microg/ml. The antibacterial activity of CZOP was good and its MIC90 against mucoid and non-mucoid strains was 8 and 16 microg/ml, respectively. CZOP and cefpirome (CPR) were the most potent against K. pneumoniae with 0.125 microg/ml of MIC90. Also, all the agents generally showed potent activities against M. (B.) catarrhalis and the MIC90 of all drugs were 4 microg/ml or less. The approximately half the number (47.5%) of the patients with respiratory infection were aged 70 years or older. As for the incidence by the diseases, bacterial pneumonia and chronic bronchitis were the highest, being noted in 35.7 and 33.8% of all the patients, respectively. The bacteria frequently isolated from the patients with bacterial pneumonia were S. pneumoniae (22.6%). In contrast, S. aureus (16.6%) and P. aeruginosa (13.7%) were relatively frequently isolated from the patients with chronic bronchitis. Before the drug administration, the bacteria frequently isolated from all the patients were H. influenzae (24.5%) and S. pneumoniae (24.2%). In comparison of the isolated bacteria by pretreatment agents, P. aeruginosa was relatively frequently isolated from the patients pretreated with cephems or macrolides and H. influenzae was relatively frequently isolated from the patients pretreated with penicillins.

Anti-Bacterial Agents↗
PubMed2003

Natural killer cell-type body cavity lymphoma following chronic active Epstein-Barr virus infection.

We describe a 69-year-old female who developed natural killer cell-type body cavity lymphoma following chronic active Epstein-Barr virus (CAEBV) infection. Examination of the patient's pleural effusion revealed large abnormal lymphocytes, which were CD2(+), CD7(+), CD30(+), CD56(+), CD3(-), and CD4(-). No rearrangement of T cell receptor genes was detected. Clonal proliferation of Epstein-Barr virus (EBV)-infected cells in pleural effusion was demonstrated by Southern blot hybridization analysis. Human herpesvirus type-8 (HHV-8) DNA was not detected in these cells. The patient achieved a complete remission with combination chemotherapy. Prior to the clinical onset of lymphoma, high fever of unknown origin had persisted for 21 months. IgG antibodies to EBV-viral capsid antigen and to EBV-early antigens, types D and R were not high (1:160 and less than 1:10, respectively). Two months after the onset of fever, however, retrospective quantitative PCR assay revealed a high EBV DNA load in plasma, indicating that CAEBV infection had been the cause of the patient's recurrent fever. The remarkable features of this case are (i) the development of lymphoma following CAEBV infection that demonstrated a normal pattern of EBV-specific antibodies, (ii) the development of HHV-8-negative body cavity lymphoma, and (iii) the effectiveness of combination chemotherapy.

Aged↗
PubMed2003

Influence of anti-ulcer drugs used in Japan on the result of (13)C-urea breath test for the diagnosis of Helicobacter pylori infection.

BACKGROUND: The (13)C-urea breath test (UBT) is a simple breath test for the diagnosis of Helicobacter pylori infection, but several factors have been reported to affect the results of this test. In this study, the effects of the antiulcer drugs used in Japan on the results of UBT were determined. METHODS: The subjects of the study were 64 adult volunteers who tested positive for H. pylori infection by the serum antibody method. Eight classes of anti-ulcer drugs used in Japan were administered at their usual doses to these subjects: lansoprazole, a proton pump inhibitor (PPI); nizatidine, an H(2)-receptor antagonist (H(2)RA); and polaprezinc, ecabet sodium, rebamipide, teprenone, cetraxate hydrochloride, and sucralfate, all mucoprotective agents. The study drugs were randomized for administration to the subjects, and each of the drugs was administered for 14 consecutive days. The UBT was performed on days 0, 14, and 21. RESULTS: The mean Delta(13)C per thousand in the lansoprazole group was significantly decreased on day 14, to below 10 per thousand, in 4 of 16 subjects, and in 1 of the 4 subjects, the test result was negative, with the Delta(13)C per thousand falling to 1.7 per thousand. The value returned to baseline 1 week after the discontinuation of lansoprazole. The other drugs administered had no significant effect on the result of the UBT, except that the mean Delta(13)C per thousand showed a tendency to decrease after the administration of ecabet sodium and rebamipide. CONCLUSIONS: Administration of a PPI may produce a false-negative UBT result, while other anti-ulcer drugs, for the most part, have little effect on the result of the UBT when used alone. The (13)C-urea breath test (UBT) is a simple test for the diagnosis of Helicobacter pylori infection, but several factors have been reported to affect the results of this test. In this study, the effects of the anti-ulcer drugs used in Japan on the results of the UBT were determined.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2003

Treatment with rokitamycin suppresses the lethality in a murine model of Escherichia coli O157:H7 infection.

The effects of rokitamycin (ROK) and levofloxacin (LEVX) were investigated in a murine model of enterohaemorrhagic Escherichia coli (EHEC) infection. After C3H/HeN mice were inoculated intragastrically with E. coli O157:H7, ROK (20mg/kg) or LEVX (1.2 mg/kg) was administered intragastrically. The death rate of the mice was noted and the faeces were collected to determine viable cell counts of EHEC and for Shiga-like toxins (SLTs) assays. After the mice were sacrificed, the kidneys and colons of some of the mice were removed for histopathological examination. The death rate of mice administered ROK (19%) was significantly lower than that of the control and LEVX-treated groups (80, 93%, respectively). Viable cell counts of EHEC in the faeces of the control and ROK-treated groups were 10(7) and 10(6) CFU/g at day 5 after the infection, respectively. LEVX reduced the bacterial count by less than 100 CFU/g at day 5. The level of SLTs in the faeces from the ROK group were lower than the LEVX-treated and control groups at day 5. The histopathological findings in the kidneys treated with LEVX showed necrotic tubular epithelial cells and those in the colon, inflammatory infiltrates. These were not seen in the ROK-treated group. These results suggested that ROK suppressed release of SLTs from the EHEC and could be useful in the treatment of EHEC infection.

Animals↗
PubMed2003

Is the recurrence of Helicobacter pylori infection after eradication therapy resultant from recrudescence or reinfection, in Japan.

BACKGROUND: Reinfection of Helicobacter pylori after eradication is rare in developed countries but most often occurs within 1 year. In the present study, we attempted to differentiate between reinfection and recrudescence of H. pylori strains between 6 months and 6 years after successful eradication in Japan, a country with a high prevalence of H. pylori infection. MATERIALS AND METHODS: After successful eradication of H. pylori, 274 patients were followed up by endoscopy and urea breath test. In recurrent patients, H. pylori strains isolated initially and after recurrence were compared using PCR-based restriction fragment length polymorphism (RFLP) analysis. RESULTS: Recurrence of H. pylori occurred in 15 of 274 patients (5.5%) at 6 months after eradication and the annual recurrence rate was 2.0% per patient year (between 1 and 6 years). PCR-based RFLP analysis of H. pylori strains isolated initially and after recurrence showed that 62.5% (at 6 months) and 100% (after 1 years) of bacteria were of different strains. CONCLUSION: Reinfection of H. pylori was not as rare at 6 months after eradication as reported previously, and up to 6 years after eradication, the annual reinfection rate is 2.0% per patient year in Japan.

Adult↗
PubMed2003

Clindamycin modulates inflammatory-cytokine induction in lipopolysaccharide-stimulated mouse peritoneal macrophages.

We investigated the mechanism by which clindamycin (CLI) modulates cytokine induction after lipopolysaccharide (LPS) stimulation. Although CLI decreased the intracellular expression levels of tumor necrosis factor alpha and interleukin 1beta (IL-1beta) and increased IL-6 expression in macrophages, cytokine mRNA expression levels were similar in CLI-treated and untreated groups. Our findings suggest that CLI modulates cytokine production in LPS-stimulated macrophages.

Animals↗
PubMed2003

Real-time PCR assay compared to nested PCR and antigenemia assays for detecting cytomegalovirus reactivation in adult T-cell leukemia-lymphoma patients.

We analyzed the efficiency of the quantitative real-time PCR assay for cytomegalovirus (CMV) reactivation in adult T-cell leukemia-lymphoma (ATL) patients and compared the results with those obtained with qualitative nested PCR and antigenemia assays. The viral load obtained by the real-time PCR assay closely paralleled the number of antigen-positive cells obtained with the antigenemia assay. Real-time PCR revealed that a large number of DNA copies could be present even in samples assessed as negative or low in antigen-positive cells (0 to 10 antigen-positive cells/50,000 cells) by antigenemia assay. CMV copy numbers did not differ between the negative and low-antigen-positive groups. When the input concentration for real-time PCR assay was 2,500 to 5,000 copies/ml, the positivity rate for the nested PCR assay was 47.3%, while the positivity rate was more than 90% at an input concentration of >/=50,000 copies/ml. Real-time PCR is more sensitive than the antigenemia and nested PCR assays. Moreover, real-time PCR was able to detect CMV reactivation earlier than the antigenemia and nested PCR assays through the use of longitudinal analysis in four ATL patients with CMV pneumonia. In longitudinal assessments, analysis of the results suggested that a cutoff level of 5,000 copies/ml might be used to initiate treatment. Real-time PCR is more suitable for monitoring CMV reactivation in ATL patients than the antigenemia and nested PCR assays. CMV viral loads of 5,000 copies/ml are proposed as the cutoff for initiating antiviral therapy in ATL patients.

Adult↗
PubMed2003

Relationship between heart rate variability and left ventricular remodeling after reperfused first anterior wall acute myocardial infarction.

The aim of the present study was to test the hypothesis that inadequate improvement in heart rate variability (HRV) in the healing stage of acute myocardial infarction (AMI) is associated with left ventricular (LV) remodeling. The study group comprised 20 patients (14 men, 6 women; mean age, 61+/-12 years) with a reperfused first anterior AMI (</=24 h). The standard deviation of normal RR intervals (SDNN) was calculated from the 24-h ambulatory electrocardiogram recorded on day 3 of admission and at predischarge from the hospital. Left ventriculography was performed immediately after primary angioplasty and at predischarge. The change in SDNN (deltaSDNN) was compared with the change in the LV end-systolic volume index (deltaLVESVI), a parameter of LV remodeling. SDNN increased from 73+/-19 ms on day 3 to 109+/-35 ms at predischarge (p=0.0003). SDNN at predicharge and deltaSDNN correlated negatively with deltaLVESVI (r=-0.52, p=0.02, and r=-0.61, p=0.004, respectively), whereas SDNN on day 3 did not correlate with deltaLVESVI. Multiple regression analysis selected deltaLVESVI (p=0.02) as an independent factor of deltaSDNN. This study indicates that deltaSDNN and SDNN at predicharge are associated with deltaLVESVI in patients with a reperfused first anterior wall AMI, indicating that persistently reduced HRV is associated with postinfarction LV remodeling.

Aged↗