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M Ogura

Publications and source records attributed to M Ogura.

At least 19 recordsLinked to original sources

DNA microarray analysis of Bacillus subtilis DegU, ComA and PhoP regulons: an approach to comprehensive analysis of B.subtilis two-component regulatory systems.

We have analyzed the regulons of the Bacillus subtilis two-component regulators DegU, ComA and PhoP by using whole genome DNA microarrays. For these experiments we took the strategy that the response regulator genes were cloned downstream of an isopropyl-beta-D-thiogalactopyranoside-inducible promoter on a multicopy plasmid and expressed in disruptants of the cognate sensor kinase genes, degS, comP and phoR, respectively. The feasibility of this experimental design to detect target genes was demonstrated by the following two results. First, expression of lacZ fusions of aprE, srfA and ydhF, the target genes of DegU, ComA and PhoP, respectively, was stimulated in their cognate sensor kinase-deficient mutants upon overproduction of the regulators. Secondly, by microarray analysis most of the known target genes for the regulators were detected and, where unknown genes were found, the regulator dependency of several of them was demonstrated. As the mutants used were deficient in the kinase genes, these results show that target candidates can be detected without signal transduction. Using this experimental design, we identified many genes whose dependency on the regulators for expression had not been known. These results suggest the applicability of the strategy to the comprehensive transcription analysis of the B.subtilis two-component systems.

Bacillus subtilis↗

Association between polymorphisms of folate- and methionine-metabolizing enzymes and susceptibility to malignant lymphoma.

Genetic alteration is considered a probable cause of malignant lymphoma. Folate and methionine metabolism play essential roles in DNA synthesis and DNA methylation, and their metabolic pathways might thus affect disease susceptibility. In the present study, 2 polymorphisms were evaluated for a folate metabolic enzyme, methylenetetrahydrofolate reductase (MTHFR), and one was evaluated for methionine synthase (MS). The 2 polymorphisms, MTHFR677 C-->T and MTHFR1298 A-->C, are reported to reduce the enzyme activity, which causes intracellular accumulation of 5,10-methylenetetrahydrofolate and results in a reduced incidence of DNA double-strand breakage. The MS2756 A-->G polymorphism also reduces the enzyme activity and results in the hypomethylation of DNA. To evaluate the association between malignant lymphoma susceptibility and these polymorphisms, hospital-based case-control study was conducted in Aichi Cancer Center. Ninety-eight patients with histologically confirmed lymphoma and 243 control subjects without cancer were evaluated. Unconditional logistic regression analyses revealed a higher susceptibility with the MTHFR677 CC and the MTHFR1298 AA genotypes (odds ratio, 2.26; 95% confidence interval, 1.26-4.02) when those harboring at least one variant allele in either polymorphism of MTHFR were defined as the reference. For the MS polymorphism, the MS2756 GG genotype also showed a higher susceptibility (odds ratio, 3.83; 95% CI, 1.21-12.1) than those with MS2756 AA or AG types. The significance was not altered when these 3 polymorphisms were evaluated in combination, and the results suggest that folate and methionine metabolism play important roles in the occurrence of malignant lymphomas. Further studies to confirm the association and detailed biologic mechanisms are now required.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

rDrak1, a novel kinase related to apoptosis, is strongly expressed in active osteoclasts and induces apoptosis.

This is the first report of a novel serine/threonine kinase, rabbit death-associated protein (DAP) kinase-related apoptosis-inducing protein kinase 1 (rDRAK1), involved in osteoclast apoptosis. We searched for osteoclast-specific genes from a cDNA library of highly enriched rabbit osteoclasts cultured on ivory. One of the cloned genes has a high homology with human DRAK1 (hDRAK1), which belongs to the DAP kinase subfamily of serine/threonine kinases. By screening a rabbit osteoclast cDNA library and 5'-RACE (rapid amplification of cDNA ends), we obtained a full length of this cDNA, termed rDRAK1. The sequencing data indicated that rDRAK1 has 88.0, 44.6, 38.7, and 42.3% identity with hDRAK1, DAP kinase, DRP-1, and ZIP (zipper-interacting protein) kinase, respectively. To clarify the role of DRAK1 in osteoclasts, we examined the effect of three osteoclast survival factors (interleukin-1, macrophage colony-stimulating factor, and osteoclast differentiation-inducing factor) on rDRAK1 mRNA expression and the effect of rDRAK1 overexpression on osteoclast apoptosis. The results suggested that these three survival factors were proved to inhibit rDRAK1 expression in rabbit osteoclasts. After transfection of a rDRAK1 expression vector into cultured osteoclasts, overexpressed rDRAK1 was localized exclusively to the nuclei and induced apoptosis. Hence, rDRAK1 may play an important role in the core apoptosis program in osteoclast.

Amino Acid Sequence↗

Nanosecond, high-intensity pulsed laser ablation of myocardium tissue at the ultraviolet, visible, and near-infrared wavelengths: in-vitro study.

BACKGROUND AND OBJECTIVE: A large number of clinical trials of transmyocardial laser revascularization (TMLR) have been conducted to treat severe ischemic heart diseases. A variety of laser sources have been used or tested for this treatment, however, no comprehensive study has been performed to reveal the mechanism and the optimum laser irradiation condition for the myocardium tissue ablation. There have been reported limited experimental data of the high-intensity pulsed laser ablation of myocardium tissues. STUDY DESIGN/MATERIALS AND METHODS: A 1064-nm Q-switched Nd:YAG laser and its 2nd (532 nm), 3rd (355 nm), and 4th (266 nm) harmonics were used for ablation experiments. At each wavelength, 25 laser pulses irradiated the porcine myocardium tissue samples at a constant laser intensity (peak laser power divided by laser spot area) of approximately 2 GW/cm(2) and the ablation depths were measured. During ablation, laser-induced optical and acoustic emissions were measured to investigate the ablation mechanism at each laser wavelength. For the ablated tissues, histological observation was made with a polarization optical microscope. RESULTS: It was shown that the ablation efficiency did not directly depend on the linear absorption coefficient of the tissue; the ablation depth was maximized at 355 and 1064 nm, and minimized at 532 nm. Strong laser-induced optical and acoustic emissions were observed for the 266- and 1064-nm laser irradiations. The histology showed that thermal denaturation of the tissue near the ablation walls decreased with decreasing wavelength for 266, 355, and 532 nm, but it was limited for 1064 nm. CONCLUSION: At the laser intensity of approximately 2 GW/cm(2), ablation characteristics were drastically changed for the different laser wavelengths. The results indicated that for 266, 355, and 532 nm, the tissue removal was achieved mainly through a photothermal process, but for 266 nm the intense laser-induced plasma formation would result in a reduced laser energy coupling to the tissue. For 1064 nm, a photodisruption was most probable as a dominant tissue removal process. Because of the high ablation rate and limited thermal denaturation, the 355- and 1064-nm lasers could be potential laser sources for TMLR, although further investigation is needed to discuss the clinical issues.

Angioplasty, Laser↗

Re-treatment of relapsed indolent B-cell lymphoma with rituximab.

The purpose of this study was to investigate the toxicity and the efficacy of re-treatment with rituximab, a chimeric mouse human anti-CD20 monoclonal antibody, in relapsed patients with indolent B-cell non-Hodgkin's lymphoma (NHL) who responded to rituximab in the previous phase I or phase II study. Thirteen patients with relapsed B-cell NHL, each of whom was confirmed to have Revised European-American Lymphoma Classification type II, 1-6 histology (indolent B-NHL), enrolled in this re-treatment study. All were re-treated with rituximab at 375 mg/m2 weekly for 4 consecutive weeks. Rituximab re-treatment was well tolerated with no grade 3/4 nonhematological toxicities, similar to that of the initial treatment. No patients developed detectable human anti-chimeric antibody. Partial responses were observed in 5 of 13 patients (38%; 95% confidence interval [CI], 14% to 68%); 6 patients showed stable disease and 2 showed progressive disease. Overall survival rate was 93% at 19 months of median follow-up after rituximab re-treatment. Median progression-free survival (PFS) after the re-treatment was 5.1 months (95% CI, 4.1 to 5.6 months), and the median PFS after the initial treatment was 8.2 months (95%CI, 5.9 to 11.3 months). Although rituximab re-treatment induced prolonged depletion of normal peripheral blood B cells in all patients, no significant decrease in serum immunoglobulin or complement level was observed. In conclusion, rituximab re-treatment was well tolerated, and it may produce a prolonged PFS in some patients with indolent B-cell NHL who showed initial response to rituximab.

Adult↗

Assessment of prognostic factors in follicular lymphoma patients.

Prognostic factors, including clinical, biological, and histological parameters, were assessed for 94 patients with follicular lymphomas at our institute. Follicular lymphomas constituted 7.7% (94/1208) of malignant lymphomas in this study. Eighteen patients were diagnosed with stage I follicular lymphoma, 20 with stage II, 23 with stage III, and 33 with stage IV. The cases of follicular lymphoma were subclassified as: follicular small cleaved cell lymphoma (FSC) in 20 cases, follicular mixed cell lymphoma (FMX) in 59 cases, and follicular large cell lymphoma (FLC) in 15 cases. The patients comprised 49 men and 45 women with a median age of 54 years (range, 25-84 years). The complete response rate was 76.5%, and the median survival time was 13 years. The expected 10-year overall survival and event-free survival rates were 61.9% and 38.2%, respectively. Univariate analysis identified the factors associated with poor survival as elevated serum lactate dehydrogenase (LDH) level (P < .0001), age of >60 (P < .0001), Ann Arbor stage III/IV (P < .01), and Eastern Cooperative Oncology Group performance status (PS) of 2 to 4 (P = .048). Multivariate analysis showed that LDH, age, and PS were independent predictors. After application of the International Prognostic Index (IPI), the 10-year survival rates for the low-risk, low-intermediate risk, high-intermediate risk and high-risk groups were 80.4%, 48.7%, 21.9%, and 0.0%, respectively. The differences among these groups were significant at P < .01. The IPI for aggressive non-Hodgkin's lymphoma was found to be applicable to survival prediction for Japanese follicular lymphoma patients.

Adult↗

CD34+-selected autologous peripheral blood stem cell transplantation conditioned with total body irradiation for malignant lymphoma: increased risk of infectious complications.

Although high-dose chemotherapy with autologous peripheral blood stem cell transplantation (autoPBSCT) has been shown or confirmed to be an effective treatment for high-risk and relapsed non-Hodgkin's lymphoma (NHL), relapse after autoPBSCT remains a serious problem. In a clinical trial to overcome relapse, we adopted a treatment plan in which PBSCs purified in vitro to CD34+ cells to deplete tumor cells (CD34+ autoPBSCT), total body irradiation (TBI) of 1200 cGy, and melphalan, 180 mg/m2, were used as a preconditioning regimen. Eighteen patients with relapsed or high-risk NHL participated in the study. This study compared the incidence of complications following CD34+ autoPBSCT preconditioned with the TBI regimen (n = 10): the TBI group; CD34+ autoPBSCT with the non-TBI regimen (n = 8): the non-TBI group; and unselected autoPBSCT with the non-TBI regimen (n = 19): the unselected autoPBSCT control group. After day 30 posttransplantation, 6 of 10 patients treated with the TBI regimen developed 11 infectious complications in total, compared with only 1 of 8 patients treated with the non-TBI regimen and 4 of 19 patients given unselected autoPBSCT. Two fatal complications occurred in the TBI group, but none occurred in the other 2 groups. The CD4+ lymphocyte count at 1 month posttransplantation was significantly lower in the TBI group than in the unselected autoPBSCT group. These findings suggest that the addition of TBI to the preconditioning regimen for CD34+ autoPBSCT is associated with an increased incidence of severe infectious complications after transplantation.

Adult↗

Ultra stable tuning fork sensor for low-temperature near-field spectroscopy.

We report on a distance control system for low-temperature scanning near-field optical microscopy, based on quartz tuning fork as shear force sensor. By means of a particular tuning fork-optical fiber configuration, the sensor is electrically dithered by an applied alternate voltage, without any supplementary driving piezo, as done so far. The sensitivity in the approach direction is 0.2nm, and quality factors up to 2850 have been reached. No electronic components are needed close to the sensor, allowing to employ it in a liquid He environment. The system is extremely compact and allows for several hours of stability at 5 K.

Journal Article↗

A case-control study on food intake of patients with recurrent aphthous stomatitis.

OBJECTIVE: This study compared food intake among patients with recurrent aphthous stomatitis (RAS) and control patients. STUDY DESIGN: A total of 2129 outpatients of a dental hospital were enrolled. Of these, 118 patients reporting RAS experiences 4 times or more during the past year (RAS group) were selected with age-matched and sex-matched control patients. The patients filled out a questionnaire about the frequency intake of 33 foods. RESULTS: Principal component factor analysis extracted 2 food intake patterns (Factor I and II). The factor weight for Factor I showed a significantly positive correlation with consumption ratios of calcium, iron, vitamin B1, and vitamin C intake to total daily intake. The median factor score for Factor I, which was calculated based on the factor weight, was significantly lower in the patients with RAS than that in the controls. CONCLUSION: We hypothesize that not only iron and vitamin B1 might be deficient in these patients but also calcium and vitamin C.

Adult↗

[Measles epidemic and investigation of the vaccination history in Chiba Prefecture in 2000. A report from Chiba epidemiological surveillance of tuberculosis and infectious diseases].

A middle-scale epidemic of measles was occurred in Chiba Prefecture, from the beginning of the year in 2000 to September. The Chiba epidemiological surveillance of tuberculosis and infectious diseases committee conducted an investigation of the vaccination history of measles patients, to obtain the prevailing situation of measles and the efficacy of the vaccination. This report summarized results of the epidemiological investigation of measles vaccination history. A total of 1,665 cases were reported during the period. The ratio of the under 1-year-old (who usually do not receive measles vaccine) to all reported cases was 11.4%. The ratio of the vaccinees for the reported cases was 11.8% and this ratio increased in the 5 years old or over. In particular, the 9-year-old age group (26.2%), and 10-14-year-old age group (23.3%) showed a higher ratio than the other age groups. These results indicate that early vaccine inoculation to the under 1-year old group and improvement of the vaccination rate are necessary to prevent measles epidemic. The results also suggest revaccination to higher age groups might be effective.

Adolescent↗

Involvement of stringent factor RelA in expression of the alkaline protease gene aprE in Bacillus subtilis.

Expression of Bacillus subtilis aprE, encoding an extracellular alkaline protease, is positively regulated by phosphorylated DegU, the regulator of a two-component regulatory system, DegS-DegU. We found that the expression of an aprE'-'lacZ fusion was greatly reduced in a disruption mutant with a mutation of relA, which encodes the stringent factor RelA. The level of DegU in the relA mutant was similar to that in the wild-type cell. A relA degU double mutation did not result in a further decrease of the aprE'-'lacZ level found in a degU single mutant. The expression of the aprE'-'lacZ fusion in the relA mutant was stimulated by multicopy degR or the degU32(Hy) and degS200(Hy) mutations that cause the stabilization of phosphorylated DegU. Furthermore, the expression of sacB'-'lacZ, which is also dependent on phosphorylated DegU, was stimulated by the relA mutation, and this stimulation was not seen in the relA degU double mutant. These results show that RelA (or its product guanosine-3',5'-bisdiphosphate [pp Gpp]) does not affect the phosphorylation of DegU and suggest that it participates in the expression of aprE and sacB through the regulation of DegU-dependent transcription.

Artificial Gene Fusion↗

Comprehensive DNA microarray analysis of Bacillus subtilis two-component regulatory systems.

It has recently been shown through DNA microarray analysis of Bacillus subtilis two-component regulatory systems (DegS-DegU, ComP-ComA, and PhoR-PhoP) that overproduction of a response regulator of the two-component systems in the background of a deficiency of its cognate sensor kinase affects the regulation of genes, including its target ones. The genome-wide effect on gene expression caused by the overproduction was revealed by DNA microarray analysis. In the present work, we newly analyzed 24 two-component systems by means of this strategy, leaving out 8 systems to which it was unlikely to be applicable. This analysis revealed various target gene candidates for these two-component systems. It is especially notable that interesting interactions appeared to take place between several two-component systems. Moreover, the probable functions of some unknown two-component systems were deduced from the list of their target gene candidates. This work is heuristic but provides valuable information for further study toward a comprehensive understanding of the B. subtilis two-component regulatory systems. The DNA microarray data obtained in this work are available at the KEGG Expression Database website (http://www.genome.ad.jp/kegg/expression).

Bacillus subtilis↗

Quantitative assessment of the pharyngeal airway by dynamic magnetic resonance imaging in obstructive sleep apnea syndrome.

Dynamic changes in the pharyngeal airway of patients with obstructive sleep apnea syndrome (OSAS) were evaluated by quantitating the findings of real-time imaging performed during wakefulness and spontaneous sleep by means of dynamic magnetic resonance imaging (MRI). Six patients with OSAS and 3 non-OSAS subjects, selected prospectively and randomly, underwent polysomnography and dynamic MRI. The cross-sectional areas of the soft palate and oropharynx and the anterior-posterior airway dimensions seen during wakefulness and spontaneous sleep were calculated by US National Institutes of Health imaging software. On the basis of a case control study, comparisons were made with age-matched and body mass index-matched obese non-OSAS snorers. Spontaneous sleep caused significant obstruction and narrowing of various sites of the pharyngeal airway in the OSAS patients, but not in the non-OSAS subjects. During wakefulness, the non-OSAS subjects showed no marked narrowing of the pharyngeal airways, whereas a transient but significant narrowing was observed in the OSAS patients. The mean values of both the cross-sectional area and the anterior-posterior diameter at the soft palate were significantly reduced by spontaneous sleep in the OSAS patients. Dynamic MRI in awake OSAS patients shows promise as a routine diagnostic tool for localizing the upper airway collapse for appropriate selection of surgical therapy.

Adult↗

Effects of soy protein on levels of remnant-like particles cholesterol and vitamin E in healthy men.

We determined the effects of soy protein isolate (SPI) intake on remnant-like particles (RLP), lipolytic enzymes, lipid transfer protein, transaminases, sex hormones, iron, calcium, and vitamin E in healthy men. In the first randomized, crossover experiment, 14 men were given either 20 g per day of SPI or nothing (control) for each 4-week segment. After 3 weeks of SPI intake, TG and RLP cholesterol levels were significantly lower than the baseline by 13.4% (p<0.05) and 9.8% (p<0.05), respectively. However, no significant change was found in total and low-density lipoprotein (LDL) cholesterol levels or the activities of lipoprotein lipase, hepatic lipase, cholesteryl ester transfer protein, and lecithin cholesterol acyltransferase. Although the levels of transaminases. testosterone, iron, and calcium did not change, the vitamin E level was reduced from the baseline by 9.7%, a significant decrease (p<0.01). In the second study, we attempted to determine the effect of vitamin E supplement taken with SPI. For each 3-week segment, 12 men were given 20 g per day of SPI, either with or without 200 mg per day of vitamin E, in a randomized crossover design. The vitamin E level was reduced by 9.2%, a significant decrease (p<0.05), after SPI intake for 3 weeks, and vitamin E supplement increased vitamin E level significantly (p<0.05). These results demonstrate that SPI intake reduces remnant lipoproteins, TG, and the plasma level of vitamin E, although vitamin E supplementation compensates for the reduction of vitamin E. Therefore the supplementation of vitamin E may be required in subjects with long-term and abundant intake of soy protein.

Adult↗

[Recent progress in the treatment of malignant lymphoma].

The present state of the art and developments in the treatment for Hodgkin's disease (HD), follicular lymphoma (FL), MALT lymphoma, and aggressive non-Hodgkin's lymphoma are reviewed. Four courses of ABVD therapy (ABVd therapy in Japan) followed by involved-field irradiation (IFRT), and 6 to 8 courses of ABVD (ABVd in Japan) are the current state art of the therapy for early stage HD and advanced stage HD, respectively. High-dose chemotherapy with autologous hematopoietic stem cell transplantation (auto-HSCT) is also the state of the art for refractory or relapsed HD within 1 year after complete remission (CR) produced by polychemotherapy. The prognosis of the patients with 3 or more International Prognostic Scores (IPS) is poor. New intensified polychemotherapy or auto-HSCT as up-front setting is under randomized phase III clinical trial in Europe and the USA. There is no state of the art therapy for indolent lymphoma including FL, or MALT. Promising results were reported from clinical studies using new anti-lymphoma drugs such as rituximab, iibritumomab, or purine analogs (cladribine and fludarabine), and auto-HSCT with effectively purged stem cells or allogeneic HSCT. These therapeutic strategies hold a possibility of cure for indolent lymphomas. Antibiotic treatment for Helicobacter pylori-positive localized gastric MALT lymphoma is the state of the art therapy. However, there is no standard therapy for advanced stage MALT lymphoma. Risk adapted therapy using the International Prognostic Index is essential for the treatment of aggressive NHL. Three courses of CHOP followed by IFRT for localized aggressive NHL and 8 courses of CHOP for the low-risk group of advanced stage aggressive NHL are the state of the art therapies, respectively. High-dose chemotherapy with auto-HSCT is also the state of the art for sensitive relapse patients with aggressive NHL. Although some clinical studies suggested that high-dose chemotherapy with auto-HSCT as up-front setting for high-intermediate or high-risk group aggressive NHL is more effective than conventional chemotherapy, the efficacy remains to be determined. The development of new therapeutic strategies with combined use of molecular targeting drugs such as rituximab, or new anti-lymphoma drugs such as purine analogs, and HSCT is desired for more effective therapy for refractory lymphomas.

Antineoplastic Combined Chemotherapy Protocols↗

[Adriamycin (doxorubicin)].

Anthracyclines have been in clinical practice since the 1960s and represent one of the most commonly used classes of anticancer drugs. Doxorubicin (adriamycin) is one of the first anthracyclines in clinical use, has a broad anti-tumor spectrum, and has been used against hematopoietic malignancies such as lymphoma, myeloma and leukemia, and solid tumors such as breast cancer, ovarian cancer and sarcomas. There are two chemotherapeutic regimens containing doxorubicin that have been established as the state of the art therapy against malignant lymphomas. One is ABVD therapy for Hodgkin's lymphoma, and the other is CHOP therapy for aggressive non-Hodgkin's lymphoma (NHL). In these regimens as well as the regimen for breast cancer, doxorubicin is delivered by bolus intravenous infusion for 30 minutes to one hour. The use of continuous infusion schedules of doxorubicin for 72 to 96 hours has been reported to reduce the incidence of cardiac toxicity somewhat, providing a pharmacokinetic basis for the hypothesis that high peak concentrations are associated with an increased incidence of cardiotoxicity. VAD regimen for myeloma, and EPOCH regimen for relapsed aggressive NHL have been reported and used. However, this approach is not widespread because of concern over compromising antitumor efficacy, unpredictable toxicities, and logistical issues. Continuous infusion schedules of doxorubicin might be reevaluated for the clinical benefit especially for patients with breast cancer treated by trastuzumab and doxorubicin, because trastuzumab was reported to enhance cardiac toxicity.

Antineoplastic Agents↗