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Biomedical subjects

Yasuhiro Suzuki

Publications and source records attributed to Yasuhiro Suzuki.

At least 91 records · Page 5Linked to original sources

Induction of mitochondrial aldehyde dehydrogenase by submergence facilitates oxidation of acetaldehyde during re-aeration in rice.

Post-hypoxic injuries in plants are primarily caused by bursts of reactive oxygen species and acetaldehyde. In agreement with previous studies, we found accumulations of acetaldehyde in rice during re-aeration following submergence. During re-aeration, acetaldehyde-oxidizing aldehyde dehydrogenase (ALDH) activity increased, thereby causing the acetaldehyde content to decrease in rice. Interestingly, re-aerated rice plants showed an intense mitochondrial ALDH2a protein induction, even though ALDH2a mRNA was submergence induced and declined upon re-aeration. This suggests that rice ALDH2a mRNA is accumulated in order to quickly metabolize acetaldehyde that is produced upon re-aeration.

Acetaldehyde↗

Expression of the activating transcription factor 3 prevents c-Jun N-terminal kinase-induced neuronal death by promoting heat shock protein 27 expression and Akt activation.

Activating transcription factor 3 (ATF3) is induced and functions both as a cellular response to stress and to stimulate proliferation in multiple tissues. However, in the nervous system ATF3 is expressed only in injured neurons. Here we reveal a function of ATF3 in neurons under death stress. Overexpression of ATF3 by adenovirus inhibits the mitogen-activated kinase kinase kinase 1 (MEKK1)-c-Jun N-Terminal Kinase (JNK)-induced apoptosis and induces neurite elongation via Akt activation in PC12 cells and superior nerve ganglion neurons. A DNA microarray study reveals that ATF3 expression and JNK activation induce expression of the heat shock protein 27 (Hsp27). Immunoprecipitation analysis and promoter assay for Hsp27 expression suggest that both ATF3 and c-Jun are necessary for transcriptional activation of Hsp27. Hsp27 expression significantly inhibits JNK-induced apoptosis as well as Akt activation in PC12 cells and superior cervical ganglion neurons. We conclude that the combination of ATF3 and c-Jun induces the anti-apoptotic factor Hsp27, which directly or indirectly activates Akt, and thereby possibly inhibits apoptosis and induces nerve elongation. Our results suggest that ATF3- and c-Jun-induced Hsp27 expression is a novel survival response in neurons under death stress such as nerve injury.

Activating Transcription Factor 2↗

TCR V beta 8+ T cells prevent development of toxoplasmic encephalitis in BALB/c mice genetically resistant to the disease.

BALB/c are genetically resistant to development of toxoplasmic encephalitis (TE) when infected with Toxoplasma gondii, whereas CBA/Ca mice are susceptible. We compared TCR Vbeta chain usage in lymphocytes infiltrated into brains between these animals following infection. TCR Vbeta8(+) cells were the most frequent T cell population in brains of infected, resistant BALB/c mice, whereas TCR Vbeta6(+) T cells were more prevalent than Vbeta8(+) T cells in brains of infected, susceptible CBA/Ca mice. Adoptive transfer of Vbeta8(+) immune T cells, obtained from infected BALB/c mice, prevented development of TE and mortality in infected athymic nude mice that lack T cells. In contrast, adoptive transfer of Vbeta6(+) immune T cells did not prevent development of TE or mortality in the nude mice. The protective activity of Vbeta8(+) immune T cells was greater than that of the total Vbeta8(-) population. In addition, Vbeta8(+) immune T cells produced markedly greater amounts of IFN-gamma than did the Vbeta8(-) population after stimulation with tachyzoite lysate Ags in vitro. Thus, Vbeta8(+) T cells appear to play a crucial role in the genetic resistance of BALB/c mice against development of TE.

Adoptive Transfer↗

Inhibitory effects of total flavones of Hippophae Rhamnoides L on thrombosis in mouse femoral artery and in vitro platelet aggregation.

Total flavones of Hippophae Rhamnoides L (TFH) are extracted from Sea buckthorn, a Chinese herbal medicine. Sea buckthorn has antioxidant, anti-ulcerogenic and hepato-protective actions, and its berry oil is reported to suppress platelet aggregation. Though it is frequently used for patients with thrombosis, the likely mechanism(s) and effects of TFH on thrombogenesis remain unclear. Thus, we have investigated the effect in-vivo of TFH on thrombogenesis and in vitro on platelet aggregation, comparing them to those of aspirin. We measured thrombotic occlusion time in a mouse femoral artery thrombosis model by the photochemical reaction between intravenously injected rose bengal and green light irradiation. In vitro platelet aggregation in whole blood was measured by single platelet counting. Thrombotic occlusion time was 8.5 +/- 0.6 min in the control group. TFH at a dose of 300 micro g/kg, intravenously administered 15 min before the rose bengal injection, significantly prolonged it to 11.6 +/- 1.0 min (P < 0.05), a similar effect on in-vivo thrombogenesis to that of aspirin. TFH at a concentration of 3.0 micro g/ml significantly (P < 0.01) inhibited in vitro platelet aggregation induced by collagen (2 micro g/ml) in a concentration dependent manner, in contrast TFH did not affect aggregation induced by arachidonic acid (80 micro M) and ADP (0.3 micro M). The results of the present study, in which TFH prevented in-vivo thrombogenesis, probably due to inhibition of platelet aggregation, suggest a possible clinical approach for the prevention of thrombosis.

Animals↗

Ability of NMDA and non-NMDA receptor antagonists to inhibit cerebral ischemic damage in aged rats.

Although stroke is a major cause of death and disability in the elderly, the inhibitory effects of neuroprotectants in acute stroke have been investigated using experimental cerebral ischemic models of young animals. Recent clinical trials have found that few neuroprotectants are effective. These observations indicate that effects in the clinical setting do not always reflect data from young animals. Thus, we compared the effects of the NMDA receptor antagonist MK-801 and of the AMPA receptor antagonist NBQX [2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinixaline] on ischemic cerebral damage in the photothrombosis model of aged and young rats. MK-801 administered immediately after MCA occlusion significantly (P<0.05) reduced the extent of cerebral damage in young, but not in aged, rats and the effects of NBQX were similar. In separate experiments, we evaluated brain damage after microinjecting NMDA or kainic acid into the cortex using a stereotaxic apparatus. We found no significant differences in focal cerebral damage caused by NMDA between young and aged rats. On the other hand, kainic acid caused all of the aged rats tested to die, but none of the young rats. Our observations indicate that NMDA and AMPA receptor antagonists are less effective in aged, than in young, rats and that cerebral damage by receptor agonists depends on the type of receptor, such as NMDA and AMPA.

Aging↗

Primary small cell carcinoma of the common bile duct, in which surgical treatment was performed after neoadjuvant chemotherapy: report of a case.

Primary small cell carcinoma of the hepatobiliary tract is rare. Most cases occur in the gallbladder or in the ampulla of Vater, and such cases in the common bile duct (CBD) are extremely rare. We herein report a case of small cell carcinoma arising in the CBD. In this case, neoadjuvant chemotherapy followed by pylorus-preserving pancreaticoduodenectomy showed an excellent response. To our knowledge, this is the first reported case of small cell carcinoma of the CBD in which a radical resection was performed after successful neoadjuvant chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

Characteristics of humic substances in the Kuji River waters as determined by high-performance size exclusion chromatography with fluorescence detection.

Direct measurement by high-performance size exclusion chromatography with fluorescence detection was applied to the characterization of humic substances in river waters from the Kuji River system, which runs through forest hills and an agricultural plain in Japan. The monitoring wavelength of excitation 320 nm and emission 430 nm corresponds to the fluorescence maxima for aquatic fulvic acid. Chromatograms of the river waters showed four peaks; each peak position was in good agreement among these samples. Peak height ratios for the samples from the upstream Kuji River and its tributaries were different from those of the midstream and downstream sections of the Kuji River, which may reflect differences in the characteristics of humic substances and other organic materials supplied from soil to river.

Chromatography, Gel↗

Posterior retroperitoneoscopic partial adrenalectomy: clinical experience in 47 procedures.

OBJECTIVES: We evaluated posterior retroperitoneoscopic partial adrenalectomy with regard to operative complications, operation time, intraoperative blood loss. PATIENTS AND METHODS: Between January 1997 and April 2002, we performed 47 posterior retroperitoneoscopic partial adrenalectomies. There were 18 males and 29 females with a mean age of 48 years (range 28-82 years). The average adrenal tumor size was 26 mm (range 10-50mm). All procedures required three trocars. RESULTS: There was no mortality and conversion rate to open surgery was 2.1%. Average operative time and average blood loss was 198.0 ml (range 71-420 ml) and 40.8 ml (range 0-1100 ml), respectively. There was a significant correlation of operative time with the number of procedures performed. However, no significant correlation was observed between intraoperative blood loss and the number of procedures. Tumor size did not correlate with intraoperative blood loss and operative time. No significant correlation was found between body mass index and operative time. The operative time in the initial 20 cases was significantly longer than that in the subsequent 26 cases. CONCLUSION: Posterior retroperitoneoscopic partial adrenalectomy is a safe and less invasive method for treatment of adrenal tumors. With improved operative technique, the time required for this procedure has been decreased.

Adenoma↗

Detection of mutations in quinolone resistance-determining regions in levofloxacin- and methicillin-resistant Staphylococcus aureus: effects of the mutations on fluoroquinolone MICs.

The minimum inhibitory concentrations (MICs) of 18 antibiotics were determined for 66 clinical isolates of staphylococci. Genotypes, mutations in the quinolone resistance-determining regions (QRDRs), and effect of efflux were determined in the 18 levofloxacin-resistant isolates, for which the MICs of levofloxacin were high (> or =8 microg/ml). The increased levofloxacin resistance mainly resulted from some combinations of mutations in the QRDRs, although NorA-mediated efflux may play a minor role in resistance. A combination of mutations in GrlA (Ser80Phe), GrlB (Pro451Ser), and GyrA (Ser84Leu) was found in 4 methicillin-resistant Staphylococcus aureus (MRSA) isolates that were unrelated genotypically. The mutations in grlA QRDR varied in the isolates classified as being in an identical pulsed-field gel electrophoresis (PFGE) group, although the grlB, gyrA, and gyrB QRDRs were the same. These results suggest that the patterns of amino acid mutations in the QRDRs can provide distinct epidemiologic information from PFGE genotypes in fluoroquinolone-resistant MRSA. A combination of at least three mutations in GrlA, GrlB, and/or GyrA is required to increase the MICs of fluoroquinolones, although all of the levofloxacin-resistant MRSA retained the MICs of sitafloxacin in the range of 1 to 2 microg/ml.

Anti-Infective Agents↗

Dietary supplementation with fermented soybeans suppresses intimal thickening.

Although soy foods have been consumed for more than 1000 y, it is only in the past 20 y that they have made inroads into Western diets. We investigated the effect of dietary supplementation with natto extracts produced from fermented soybeans on intimal thickening of arteries after vessel endothelial denudation. Natto extracts include nattokinase, a potent fibrinolytic enzyme having four times greater fibrinolytic activity than plasmin. Intimal thickening was induced in the femoral arteries by intravenous infusion of rose bengal followed by focal irradiation with a transluminal green light. Dietary natto extract supplementation was started 3 wk before endothelial injury and continued for another 3 wk after. In ex vivo studies, euglobulin clot lysis times were measured 3 wk after the initial supplementation. Neointima formation and thickening were also initiated successfully. The intima media ratio 3 wk after endothelial injury was 0.15 +/- 0.03 in the control group. Dietary natto extract supplementation suppressed intimal thickening (0.06 +/- 0.01; P < 0.05) compared with the control group. Natto extracts shortened euglobulin clot lysis time, suggesting that their thrombolytic activities were enhanced. These findings suggest that natto extracts, because of their thrombolytic activity, suppress intimal thickening after vascular injury as a result of the inhibition of mural thrombi formation.

Animals↗

PCR-based identification of common dermatophyte species using primer sets specific for the DNA topoisomerase II genes.

BACKGROUND: We have determined nucleotide sequences of the DNA topoisomerase II genes of the dermatophyte species, and conducted a PCR-based identification system using species-specific primers for the nucleotide sequences. OBJECTIVE: To identify the major dermatophytes, Trichophyton rubrum, T. mentagrophytes, T. violaceum, M. gypseum, M. canis and E. floccosum, by PCR amplifications at the species level, without determining the nucleotide sequence. METHODS: For PCR-based identification of the major dermatophyte species, a common primer set (dPsD1) for these species and species-specific primer sets (PsT and PsME) for each species were designed based on the genomic sequences of the DNA topoisomerase II genes of the dermatophytes, and tested for their specificities in PCR amplifications. The method consisted of amplification of the genomic DNA topoisomerase II gene by the common primer set, followed by a second PCR with the primer sets consisting of species-specific primers for each dermatophyte species. RESULTS: Using dPsD1, a DNA fragment of 3390 bp was amplified from the genomic DNA of all the dermatophyte species. In the subsequent nested PCR using species-specific primer sets (PsT and PsME), both sets amplified unique sizes of PCR products, all of which corresponded to a species of the dermatophytes even in the presence of other fungal DNA. CONCLUSION: We demonstrate that the PCR-based identification targeting the DNA topoisomerase II gene is rapid and simple, and is available as a tool for the identification of the major dermatophyte species.

Arthrodermataceae↗

Species-identification of dermatophytes Trichophyton, Microsporum and Epidermophyton by PCR and PCR-RFLP targeting of the DNA topoisomerase II genes.

BACKGROUND: We have focused on the DNA topoisomerase II genes of pathogenic fungi and have previously applied polymerase chain reaction (PCR)-based identification of several species including the some of the major dermatophyte species. OBJECTIVE: To identify the dermatophytes (18 species) to a species level by PCR and PCR-restriction fragment length polymorphism (RFLP) techniques, without determining the nucleotide sequence. METHODS: The genomic DNAs of the dermatophytes (ten species of Trichophyton, seven species of Microsporum, and Epidermaphyton floccosum) were amplified by PCR using a common primer set (dPsD1) for the dermatophytes, followed by nested PCR using other primer sets (dPsD2, PsT and PsME) that contained primers specific for the DNA topoisomerase II genes of the dermatophytes. PCRs using PsT and PsME were used for the species-identification of Trichophyton, Microsporum and E. floccosum. The PCR products generated by dPsD2 were digested with restriction enzymes (Hinc II, Hinf, Afl II and PflM I), and the restriction profiles were analyzed. RESULTS: Of the eighteen species of dermatophytes, five species (T. rubrum, T. violaceum, M. canis, M. gypseum and E. floccosum) were specifically identified by the PCR using PsT and PsME to the species level, and the remaining species were identified by the unique restriction profiles for each species in the PCR-RFLP analysis, except that the restriction profile of T. mentagrophytes var. interdigitale was identical to that of T. mentagrophytes var. quinckeanum. CONCLUSION: PCR and PCR-RFLP techniques targeting the DNA topoisomerase II gene are simple and rapid, and quite useful as tools for the identification of dermatophytes to the species level.

DNA Topoisomerases, Type II↗

Sexual recombination and clonal evolution of virulence in Toxoplasma.

The protozoan parasite Toxoplasma gondii is endemic worldwide. For such a widespread pathogen that has few geographic or host boundaries, it possess an unexpected population structure comprised principally of three clonally propagated lineages. The origin and the evolutionary dynamics of these three lines are unclear. Recent population genetic analyses suggest that a meiotic recombination between two discrete gene pools produces a pandemic outbreak of three super-successful lines, which have recently come to dominate most other strains worldwide.

Animals↗

Localization and hormonal control of serine dehydratase during metabolic acidosis differ markedly from those of phosphoenolpyruvate carboxykinase in rat kidney.

Serine dehydratase (SDH) is abundant in the rat liver but scarce in the kidney. When administrated with dexamethasone, the renal SDH activity was augmented 20-fold, whereas the hepatic SDH activity was affected little. In situ hybridization and immunohistochemistry revealed that SDH was localized to the proximal straight tubule of the nephron. To address the role of this hormone, rats were made acidotic by gavage of NH(4)Cl. Twenty-two hours later, the SDH activity was increased three-fold along with a six-fold increment in the phosphoenolpyruvate carboxykinase (PEPCK) activity, a rate-limiting enzyme of gluconeogenesis. PEPCK, which is localized to the proximal tubules under the normal condition, spreads throughout the entire cortex to the outer medullary rays by acidosis, whereas SDH does not change regardless of treatment with dexamethasone or NH(4)Cl. When NH(4)Cl was given to adrenalectomized rats, in contrast to the SDH activity no longer increasing, the PEPCK activity responded to acidosis to the same extent as in the intact rats. A simultaneous administration of dexamethasone and NH(4)Cl into the adrenalectomized rats fully restored the SDH activity, demonstrating that the rise in the SDH activity during acidosis is primarily controlled by glucocorticoids. The present findings clearly indicate that the localization of SDH and its hormonal regulation during acidosis are strikingly different from those of PEPCK.

Acidosis↗

Collapsin response mediator protein-2 accelerates axon regeneration of nerve-injured motor neurons of rat.

The rat collapsin response mediator protein-2 (CRMP-2) is a member of CRMP family (CRMP-1-5). The functional consequence of CRMP-2 during embryonic development, particularly in neurite elongation, is relatively understood; however, the role in nerve regeneration is unclear. Here we examined the role of CRMP-2 during nerve regeneration using rat hypoglossal nerve injury model. Among the members, CRMP-1, CRMP-2, CRMP-5 mRNA expressions increased after nerve injury, whereas CRMP-3 and CRMP-4 mRNA did not show any significant change. In the N1E-115 cells, CRMP-2 has the most potent neurite elongation activity among the CRMP family members. In dorsal root ganglion (DRG) organ culture, CRMP-2 overexpression by adenoviral vector demonstrated substantial neurite elongation. On the other hand, CRMP-2 (DeltaC381), which acts as a dominant negative form of CRMP-2, inhibited neurite formation. Collectively, it would be plausible that CRMP-2 has potent nerve regeneration activity after nerve injury. We therefore examined whether CRMP-2 overexpression in the injured hypoglossal motor neurons accelerates nerve regeneration. A retrograde-tracer, Fluoro-Gold (FG), was used to evaluate the number of reprojecting motor neurons after nerve injury. CRMP-2-overexpressing motor neurons demonstrated the accelerated reprojection. The present study suggests that CRMP-2 has potent neurite elongation activity in nerve regeneration in vivo.

Animals↗

Promoting GMP implementation: developing training materials for the international audience.

This paper outlines the development of a CD-ROM training package entitled: The WHO Basic Training Modules on GMP, intended to support the creation of training courses aimed particularly at government compliance officials who inspect pharmaceutical manufacturing facilities. The material was created over a three-year period in collaboration with a team of external experts, WHO regional and local offices, and Drug Regulatory Authorities of participating countries. The nine training workshops and courses that contributed to the development and evaluation processes were attended by approximately 240 participants from 47 countries. To date over 5,800 copies of the CD-ROM have been distributed.

CD-ROM↗

Combination of trastuzumab and vinorelbine in metastatic breast cancer.

BACKGROUND: Since the clinical introduction of trastuzumab (Herceptin) for metastatic breast cancers that overexpress human epidermal growth factor receptor 2 (HER2), this anticancer agent has played an important role in breast cancer treatment. We examined the effects of trastuzumab and vinorelbine (Navelbine) as a second- or third-line therapy in 24 patients whose HER2-positive tumors did not respond to or relapsed after administration of trastuzumab alone or in combination with taxane. METHODS: Trastuzumab was administered at 2 mg/kg (loading dose 4 mg/kg) once weekly and vinorelbine at 25 mg/m(2) once weekly. The median treatment duration was 118.5 days (range, 22-351 days). RESULTS: The response rate was 42% (95% confidence interval (CI): 22%-63%). The adverse events of NCI-CTC grade 3 or above consisted of neutropenia in three patients; other adverse events, including vasculitis, generalized fatigue, anemia and thrombocytopenia, were grade 1 or 2. All adverse events were reversible after treatment withdrawal and were easily manageable. CONCLUSION: A combination of trastuzumab and vinorelbine can be safely administered on an outpatient basis, and is useful in the treatment of patients with HER2-overexpressing metastatic breast cancer.

Adult↗