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Biomedical subjects

J Suzuki

Publications and source records attributed to J Suzuki.

At least 37 records · Page 2Linked to original sources

Discrete change of spin-density-wave modulation in Cr(100)/Sn multilayers as a function of Cr layer thickness.

Magnetic structures of epitaxial Cr(001)/Sn multilayers, where monatomic Sn layers are periodically embedded in a Cr(001) film, were studied using neutron diffraction and Mössbauer spectroscopy. It was found that spin-density-wave (SDW) antiferromagnetic structures with the modulation along the perpendicular direction to the film plane are stabilized at low temperatures. The wavelength of the SDW discretely changes as a function of the superlattice period. The enhanced magnetic moments of Cr at the Cr/Sn interfaces are thought to pin the antimode of the SDW modulation at the interface, resulting in the SDW with the modulation harmonic to the superlattice period.

Journal Article↗

Measurements of cosmic-ray low-energy antiproton and proton spectra in a transient period of solar field reversal.

The energy spectra of cosmic-ray low-energy antiprotons ( *p's) and protons ( p's) have been measured by BESS in 1999 and 2000, during a period covering reversal at the solar magnetic field. Based on these measurements, a sudden increase of the *p/p flux ratio following the solar magnetic field reversal was observed, and it generally agrees with a drift model of the solar modulation.

Journal Article↗

Yersinia pseudotuberculosis infection in breeding monkeys: detection and analysis of strain diversity by PCR.

In the last three decades, several monkeys reared in outdoor/indoor-outdoor breeding colonies and cages of the Primate Research Institute, Kyoto University, died of yersiniosis caused by Yersinia pseudotuberculosis, necessitating introduction of a method to detect the bacteria rapidly and thus allow preventive measures to be undertaken. A rapid nested polymerase chain reaction (PCR) method for identification of Y. pseudotuberculosis in fecal samples and a random amplified polymorphic DNA (RAPD)-PCR approach for distinguishing between bacterial strains were therefore developed. Yersinia pseudotuberculosis isolates from monkey specimens were found to be classifiable into several types. To determine the source of infection, hundreds of fecal samples of wild rats, pigeons, and sparrows were collected from around the breeding colonies and cages, and subjected to PCR analyses. Yersinia pseudotuberculosis was detected in 1.7% of the fecal samples of wild rats. The DNA fingerprints of the bacteria revealed by RAPD-PCR were the same as that of one strain isolated from macaques, suggesting the wild rat to be a possible source of infection.

Adhesins, Bacterial↗

Beneficial effects of tea catechins on diet-induced obesity: stimulation of lipid catabolism in the liver.

OBJECTIVE: Obesity has increased at an alarming rate in recent years and is now a worldwide health problem. We investigated the effects of long-term feeding with tea catechins, which are naturally occurring polyphenolic compounds widely consumed in Asian countries, on the development of obesity in C57BL/6J mice. DESIGN: We measured body weight, adipose tissue mass and liver fat content in mice fed diets containing either low-fat (5% triglyceride (TG)), high-fat (30% TG), or high-fat supplemented with 0.1-0.5% (w/w) tea catechins for 11 months. The beta-oxidation activities and related mRNA levels were measured after 1 month of feeding. RESULTS: Supplementation with tea catechins resulted in a significant reduction of high-fat diet-induced body weight gain, visceral and liver fat accumulation, and the development of hyperinsulinemia and hyperleptinemia. Feeding with tea catechins for 1 month significantly increased acyl-CoA oxidase and medium chain acyl-CoA dehydrogenase mRNA expression as well as beta-oxidation activity in the liver. CONCLUSION: The stimulation of hepatic lipid metabolism might be a factor responsible for the anti-obesity effects of tea catechins. The present results suggest that long-term consumption of tea catechins is beneficial for the suppression of diet-induced obesity, and it may reduce the risk of associated diseases including diabetes and coronary heart disease.

Adipose Tissue↗

Efficacy of school urinary screening for membranoproliferative glomerulonephritis type 1.

AIMS: In order to evaluate the efficacy of a school urinary screening programme, children with membranoproliferative glomerulonephritis (MPGN) type 1 were studied. METHODS: A total of 52 patients who had been diagnosed with MPGN type 1 from 1970 to 1997 were studied; 35 were identified after 1974 on screening (group S), and 17 were identified by presenting symptoms (group N), mostly before 1989. RESULTS: Mean blood pressure was 89 mm Hg in group S and 104 mm Hg in group N; urinary protein excretion was 0.9 g/day in group S and 3.0 g/day in group N. Histopathological evidence of chronic changes was found in six group S and 15 group N patients. No patients in group S had renal insufficiency, but five patients in group N required regular haemodialysis. CONCLUSIONS: Results suggest that early identification by school urinary screening may enable early management and so improve prognosis of MPGN.

Adolescent↗

Creatinine inhibits D-amino acid oxidase.

Inhibition of D-amino acid oxidase (DAO) activity by various uremic retention products and guanidino compounds was investigated. Creatinine (CTN) was found to inhibit DAO at a similar concentration in the sera of uremic patients. The inhibition was competitive and the K(i) value was 2.7 mM. Moreover, CTN was shown to interact with flavin adenine dinucleotide (FAD), a coenzyme of DAO. The UV spectral change of FAD bound to DAO was observed in the visible region by addition of CTN. These findings suggest that the increase in serum and tissue CTN concentrations might be responsible, in part, for the increase in D-amino acids in the sera of uremic patients.

Alanine↗

Roles of angiotensin II type 2 receptor stimulation associated with selective angiotensin II type 1 receptor blockade with valsartan in the improvement of inflammation-induced vascular injury.

BACKGROUND: To investigate the effect of angiotensin (Ang) II type 1 receptor (AT(1)) blocker on vascular remodeling and explore the possibility of the involvement of Ang II type 2 receptor (AT(2)) stimulation in this process, we examined the effects of the selective AT(1) blocker valsartan on the vascular injury in wild-type (Agtr2+) and AT(2)-null (Agtr2-) mice. METHODS AND RESULTS: Neointima formation and the proliferation of vascular smooth muscle cells (VSMCs) induced by cuff placement on the femoral artery were greater in Agtr2- mice than those in Agtr2+ mice. Treatment of mice with valsartan at a dose of 1 mg. kg(-1). d(-1), which did not influence systolic blood pressure, significantly decreased neointima formation and the proliferation of VSMCs, whereas the valsartan was less effective in Agtr2- mice. Moreover, cuff placement increased the expression of monocyte chemoattractant protein-1 (MCP-1); inflammatory cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-1beta; and infiltration of CD45-positive leukocytes and macrophages in the injured arteries and further enhanced them in Agtr2- mice, suggesting the antagonistic effects of AT(1) and AT(2) for vascular inflammation. Valsartan attenuated the expression of MCP-1, TNF-alpha, IL-6, IL-1beta, and infiltration of leukocytes and macrophages in the injured arteries; however, these effects of valsartan were less prominent in Agtr2- mice. CONCLUSIONS: These results suggest that the stimulation of the AT(2) receptor after AT(1) blockade is important in the improvement of the inflammatory vascular injury.

Angiotensin I↗

cis Element decoy against nuclear factor-kappaB attenuates development of experimental autoimmune myocarditis in rats.

Nuclear factor-kappaB (NFkappaB) plays a significant role in the coordinated transactivation of cytokine, inducible NO synthase (iNOS), and adhesion molecule genes. Although inflammation is an essential pathological feature of myocarditis, the role of NFkappaB in this process remains obscure. We examined the role of NFkappaB in the progression of rat experimental autoimmune myocarditis (EAM) and tested the hypothesis that NFkappaB blockade with a decoy against the cis element of NFkappaB can prevent the progression of EAM. Lewis rats were immunized with purified porcine cardiac myosin to establish EAM on day 0. NFkappaB decoy was infused into the rat coronary artery on day 0 (group NF0), 7 (group NF7), or 14 (group NF14) and harvested on day 21. Scrambled decoy was infused on day 0 (group SD0), 7 (group SD7), or 14 (group SD14) and served for control groups. The ratios of myocarditis-affected areas to the ventricular cross-sectional area of all treatment groups were significantly lower than those of the control groups (group NF0, 33+/-18% versus SD0, 53+/-14%; group NF7, 19+/-15% versus SD7, 50+/-16%; and group NF14, 34+/-10% versus SD14, 52+/-14%). Immunohistochemical and immunoblot analyses showed expression of ICAM-1, iNOS, IL-2, and TNFalpha in myocardium of scrambled decoy groups, and this expression was effectively suppressed by NFkappaB decoy treatment. Thus, we found that NFkappaB is a key regulator in the progression of EAM and that in vivo transfection of NFkappaB decoy reduces the severity of EAM.

Animals↗

Enantioselective ring cleavage of dioxane acetals mediated by a chiral Lewis acid: application to asymmetric desymmetrization of meso-1,3-diols.

[reaction: see text]. Phenylalanine-derived B-aryl-N-tosyloxazaborolidinones selectively activate one of two enantiotopic oxygen atoms in prochiral anti dioxane acetals derived from meso-1,3-diols, leading to enantioselective formation of ring-cleavage products. The reaction is utilized as a key step in asymmetric desymmetrization of meso-1,3-diols.

Journal Article↗

Smad7 is induced by norepinephrine and protects rat hepatocytes from activin A-induced growth inhibition.

Activin A induces growth arrest of rat hepatocytes in vitro and in vivo. The alpha(1)-adrenergic agonist, norepinephrine (NE), enhances epidermal growth factor-stimulated DNA synthesis and inhibits activin A-induced growth inhibition, but the mechanisms of these actions are unclear. Smad proteins have recently been identified as intracellular signaling mediators of transforming growth factor-beta family members. In the present study, we explored how NE modulates the Smad signaling pathway in rat cultured hepatocytes. We demonstrate that NE inhibits activin A-induced nuclear accumulation of Smad2/3 and that NE rapidly induces inhibitory Smad7 mRNA expression. Infection of Smad7 adenovirus into rat hepatocytes inhibited activin A-induced nuclear accumulation of Smad2/3, enhanced epidermal growth factor-stimulated DNA synthesis, and abolished the growth inhibitory effect of activin A. We also demonstrated that the induction of Smad7 by NE is dependent on nuclear factor-kappa B (NF-kappa B). The amount of active NF-kappa B complex rapidly increased after NE treatment. Preincubation of the cells with an NF-kappa B pathway inhibitor N-tosyl-l-phenylalanine chloromethyl ketone or infection of the cells with an adenovirus expressing an I kappa B super-repressor (Ad5I kappa B) abolished the NE-induced Smad7 expression. These results indicate a mechanism of transmodulation between the Smad and trimeric G protein signaling pathways in rat hepatocytes.

Activins↗

Prevention of anti-IgM-induced apoptosis accompanying G1 arrest in B lymphoma cells overexpressing dominant-negative mutant form of c-Jun N-terminal kinase 1.

A family of mitogen-activated protein (MAP) kinases comprising the extracellular signal-regulated kinases (ERKs), c-Jun N-terminal kinases (JNKs), and p38 MAP kinases are involved in proliferation and apoptosis. However, there are some arguments concerning the role of these kinases in Ag-induced B cell apoptosis. Two of the B lymphoma cell lines (CH31 and WEHI-231) susceptible to anti-IgM-induced apoptosis were used as a model. To address these issues, we examined the kinetics of anti-IgM-induced activation of MAP kinases and established cell lines overexpressing a dominant-negative (dn) mutant form of JNK1 (dnJNK1). Anti-IgM induced a sustained JNK1 activation with a peak at 8 h, with a marginal activation of ERK1/ERK2 in CH31 cells. The sustained JNK1 activation was not a secondary event through a caspase activation. The peak point of the JNK1 activation was just before the onset of a decline in mitochondrial membrane potential, which preceded anti-IgM-induced cell death. Following anti-IgM stimulation, dnJNK1 prevented a decline in mitochondrial membrane potential at 24 h, with a prolonged inhibition up to 72 h in WEHI-231, although it did so only partially during a later time period in CH31. The dnJNK1 cells also demonstrated diminished procaspase-3 activation and a decreased rate of apoptosis upon anti-IgM stimulation, with a concomitant increased arrest in G(1) phase, which could be explained by enhanced levels of cyclin-dependent kinase inhibitor p27(Kip1) protein. Thus, anti-IgM-induced JNK activation might be implicated in cell cycle progression as well as in apoptosis regulation, probably involving p27(Kip1) protein.

Amino Acid Chloromethyl Ketones↗

Toward the bioremediation of dioxin-polluted soil: structural and functional analyses of in situ microbial populations by quinone profiling and culture-dependent methods.

In order to obtain basic information toward the bioremediation of dioxin-polluted soil, microbial communities in farmland soils polluted with high concentrations of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) were studied by quinone profiling as well as conventional microbiological methods. The concentration of PCDD/Fs in the polluted soils ranged from 36 to 4,980 pg toxicity equivalent quality (TEQ) g(-1) dry weight of soil. There was an inverse relationship between the levels of PCDD/Fs and microbial biomass as measured by direct cell counting and quinone profiling. The most abundant quinone type detected was either MK-6 or Q-10. In addition, MK-8, MK-8(H2), and MK-9(H8) were detected in significant amounts. Numerical analysis of quinone profiles showed that the heavily polluted soils (> or = 1,430 pg TEQ g(-1)) contained different community structures from lightly polluted soils (< or = 56 pg TEQ g(-1)). Cultivation of the microbial populations in the heavily polluted soils with dibenzofuran or 2-chlorodibenzofuran resulted in enrichment of Q-10-containing bacteria. When the heavily polluted soil was incubated in static bottles with autoclaved compost as an organic nutrient additive, the concentrations of PCDD/Fs in the soil were decreased by 22% after 3 months of incubation. These results indicate that dioxin pollution exerted a significant effect on microbial populations in soil in terms of quantity, quality, and activity. The in situ microbial populations in the dioxin-polluted soil were suggested to have a potential for the transformation of PCDD/Fs and oxidative degradation of the lower chlorinated ones thus produced.

Biodegradation, Environmental↗

Early growth-response factor 1 and basic transcriptional element-binding protein 2 expression in cardiac allografts.

Early growth-response factor 1 (Egr-1) and basic transcriptional element-binding protein 2 (BTEB2) are transcriptional factors that regulate multiple genes involved in phenotypic changes of smooth muscle cells (SMCs), one of the outstanding pathologic features of chronic cardiac allograft rejection. In this study, we used a heterotopic abdominal heart transplant model in monkeys to evaluate the roles of these molecules in graft coronary vasculopathy. We demonstrated that Egr-1 and BTEB2 are induced in vascular SMCs of rejected cardiac allografts well before morphologic changes, such as intimal thickening. These findings suggest that expression of Egr-1 and BTEB2 is one of the initial events in allograft angiopathy.

Animals↗

Identification of rab7 as a melanosome-associated protein involved in the intracellular transport of tyrosinase-related protein 1.

The melanosome is a unique secretory granule of the melanocyte in which melanin pigments are synthesized by tyrosinase gene family glycoproteins. Melanogenesis is a highly regulated process because of its inherent toxicity. An understanding of the various regulatory mechanisms is important in delineating the pathophysiology involved in pigmentary disorders and melanoma. We have purified and analyzed the total melanosomal proteins from B16 mouse melanoma tumors in order to identify new proteins that may be involved in the control of the melanogenesis process. Melanosomal proteins were resolved by two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis, a predominant spot (27 kDa with isoelectric point 5.8-6.4) was excised and digested with cyanogen bromide, and the fragments were sequenced. Synthetic oligonucleotide primers were synthesized corresponding to the peptide sequences, and reverse transcriptase polymerase chain reaction amplification of total RNA from B16 cells was carried out. Sequencing of one of the polymerase-chain-reaction-mediated clones demonstrated 80%-97% sequence homology of 200 bp nucleotide with GTP-binding proteins at the 3'-untranslated region. GTP-binding assay on two-dimensional gels of melanosomal proteins showed the presence of several (five to six) small GTP-binding proteins, suggesting that small GTP-binding proteins are associated with the melanosome. Among the known GTP-binding proteins with similar molecular weight and isoelectric point ranges, rab3, rab7, and rab8 were found to be present in the melanosomal fraction by immunoblotting. Confocal immunofluorescence microscopy showed that rab7 is colocalized with the tyrosinase-related protein 1 around the perinuclear area as well as, in part, in the perikaryon, thereby suggesting that rab7 might be involved in the intracellular transport of tyrosinase-related protein 1. Tyrosinase-related protein 1 transport was blocked by the treatment of B16 cells with antisense oligonucleotide to rab7. We suggest (i) that rab7 is a melanosome-associated molecule, (ii) that tyrosinase-related protein 1 is present in late-endosome delineated granules, and (iii) that rab7 is involved in the transport of tyrosinase-related protein 1 from the late-endosome delineated granule to the melanosome.

Animals↗

Time-course changes in arteriolar and venular portions of capillary in young treadmill-trained rats.

This study was designed to examine the time-course changes in capillarity, especially the distribution of arteriolar and venular capillaries, in skeletal muscles during endurance training by running in young female Wistar rats. Exercise training by running started at the age of 5 weeks and lasted for 5 weeks at 25 m min(-1) on a 25% gradient, 10-60 min day(-1), 5 days per week. Morphological findings were obtained from the soleus (SOL) and deep portions of the medial gastrocnemius (GASd) muscles. In SOL, the training significantly increased the capillary-to-fibre ratio (C:F), total capillary density, and density of venular capillaries at Week 1. Significant increases in the C:F and total capillary density were also observed at Weeks 4 and 5. The capillary domain area (CDA) values for total capillary and arteriolar and venular capillaries were significantly decreased after 4 weeks of training. In GASd, the training significantly increased the C:F at Week 1 and from Week 3 onwards. It also significantly increased cross-sectional area of all fibre types. Total capillary density and the CDA values showed no significant difference between control and training groups at all points of time. Significant increases in succinate dehydrogenase (SDH) activity were first noted after 2 weeks in GASd and after 3 weeks in SOL. These findings suggest that, in young growing rats, adaptive changes in the oxygen transport system occurred within 1 week after the onset of training mainly in highly oxidative muscles. The changes in arteriolar and venular capillary densities may help to clarify the growth pattern of the capillary network associated with endurance running training.

Animals↗

Identification of Th2-type suppressor T cells among in vivo expanded ocular T cells in mice with experimental autoimmune uveoretinitis.

Experimental autoimmune uveoretinitis (EAU), which is a T cell mediated organ specific autoimmune disease, is induced by immunization with interphotoreceptor retinoid binding protein (IRBP) in susceptible strains of mice. It has been found that IRBP-derived peptide 518-529 (p518-529) generates Th2-type responses and inhibits IRBP-induced EAU, indicating that the p518-529 might be an epitope for suppressor T cells in IRBP-induced EAU. First, we observed that there were T cells producing the Th2 type cytokines such as IL-4 and IL-10 in late phase of EAU. Furthermore, to examine whether p518-529-reactive T cells expand in the eye during EAU, T cell receptor (TCR) of ocular T cells was compared with that of p518-529 reactive T cells in spleen from mice with EAU by PCR-single strand conformation polymorphism (PCR-SSCP) and nucleotide sequence analysis. SSCP and sequence analyses indicated that p518-529 reactive TCR BV10+ T cells bearing amino acid motif(PWG) and TCR BV13+ T cells bearing amino acid motif(PGLGGY) in their complementary-determining region 3 (CDR3) region were clonally expanding in ocular tissues on day 28 after immunization, although these T cells were not detected on day 14. These findings demonstrate that p518-529 reactive Th2-type T cells expand oligoclonally in the uveitic eyes in the late stage of EAU and may function as Th2-type suppressor T cells for improvement of the disease.

Amino Acid Motifs↗

A survey on the drug therapy for delirium.

Delirium, which is experienced by 10-30% of inpatients, is commonly seen in daily practice. A survey was conducted of the delirium medications, and results were obtained from 28 psychiatric departments and related facilities. Haloperidol was used in 67% cases for the treatment of delirium. Ninety-seven per cent of facilities considered haloperidol as the drug of first choice, while 57% thought this drug had few side-effects and was easy to use. However, because the use of this drug is not covered by health insurance in Japan, its use is limited. We expect that this study on medication for the treatment of delirium will be a first step in increasing the approved indications for drugs used for the treatment of delirium, and to reduce off-label use.

Antipsychotic Agents↗