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Biomedical subjects

A Suzuki

Publications and source records attributed to A Suzuki.

At least 235 records · Page 13Linked to original sources

A topographic electrophysiologic study of mental rotation.

Mental rotation is a task performed when subjects are requested to determine whether two stimuli presented in turn have the same shape (congruency) or a mirror-image shape (incongruency) regardless of any difference in orientation. We compared event-related potentials during mental rotation tasks with narrow and wide angular disparities between the two stimuli to identify electrophysiologic correlates of mental rotation. When angular disparity was wide, a prominent negative component arose 438 ms after the second stimulus. A statistically significant difference detected between amplitudes of the negative components under narrow- and wide-angle conditions was maximal in the right parietal region, suggesting that processing of mental rotation is a right parietal dominant function.

Adult↗

New plasma-reduced synthetic media, Fukushima cocktails, for the storage of platelets for transfusion.

BACKGROUND: Donor plasma proteins are associated with non-hemolytic allergic reactions, such as urticaria or laryngeal edema, in platelet-transfusion recipients. Replacement of plasma with synthetic media from platelet concentrates (PCs) is considered to be effective in preventing such reactions. However, platelets preserved in media depleted of less than 10% plasma are reported to have functions inferior to those preserved in plasma. METHODS: Fukushima Cocktails (FCs) contain glycerol (25, 50 or 100mM), sodium acetate, glucose and other components. To test the effect and determine the most suitable concentration of glycerol for platelet preservation, functions of platelets including aggregation, hypotonic shock response and swirling pattern and released biochemicals were measured with platelets preserved in Fukushima Cocktails. The effects of residual plasma on platelet functions were also evaluated. Autologous platelets stored for 3 days in solution containing 50 mM glycerol were transfused into healthy volunteer donors to evaluate their safety and survival. RESULTS: The functions (aggregation and hypotonic shock response) of platelets preserved in Fukushima Cocktails with 10% residual plasma were preserved for 5-7 days as well as plasma controls, whereas platelets stored for 9 days in a medium lacking glycerol became swollen and beta-thromboglobulin and thromboxane B(2) increased. When the residual plasma was more than 5%, platelet functions including aggregation, hypotonic shock response and swirling pattern were well preserved for 7 days. The in vivo platelet survival rates at 24 and 48 h after transfusion of platelets stored for 3 days in Fukushima Cocktail were 77% and 60%, respectively, which were not less than autologous plasma-stored platelets. CONCLUSION: Glycerol at a concentration of around 50 mM has a beneficial effect on platelet preservation for more than 7 days. The results of these experiments indicate that platelets stored in Fukushima Cocktail should be useful clinically.

Blood Platelets↗

Xenopus embryonic E2F is required for the formation of ventral and posterior cell fates during early embryogenesis.

Using an expression cloning approach, we have unveiled a novel function for the transcription factor E2F. We demonstrate that Xenopus E2F (xE2F) is required for patterning of the Xenopus embryonic axis. Overexpression of xE2F in embryos induces ectopic expression of ventral and posterior markers, including selected members of the Hox genes, and suppresses the development of dorsoanterior structures. Loss of xE2F function in embryos leads to the elimination of ventral and posterior structures. These observations suggest that xE2F acts as an important regulator of region-specific gene expression and in the formation of the embryonic axis. This study provides evidence for an additional embryonic function for E2F, independent of its well-documented role in cell cycle regulation, and suggests a novel mechanism of region-specific gene expression during vertebrate embryogenesis.

Amino Acid Sequence↗

Effect of 6-O-sulfonate hexosamine residue on anticoagulant activity of fully O-sulfonated glycosaminoglycans.

Intact and fully O-sulfonated glycosaminoglycans (GAGs) including chondroitin sulfate, dermatan sulfate, hyaluronan, heparan sulfate and heparin were chemically de-O-sulfonated on their hexosamine C-6 position (6-O-desulfonation) using N,O-bis(trimethylsilyl) acetamide. 1H NMR spectroscopy and chemical compositional analysis showed that the chemical de-O-sulfonation at C-6 position of hexosamine residues in both intact and fully O-sulfonated GAGs was completely achieved. Since GAGs and their derivatives are often used as anticoagulant agents, their anti-amidolytic activities were determined. While most of anticoagulant activity of fully O-sulfonated GAGs (FGAGs) and heparin disappeared following chemical 6-O-desulfonation, the activity of 6-O-desulfonated fully O-sulfonated dermatan sulfate (De6FDS) remained. This observation suggests the importance of the position of O-sulfonate groups for anti-coagulant activity.

Anticoagulants↗

Lack of antibody production against Hanganutziu-Deicher (H-D) antigens with N-glycolylneuraminic acid in patients with porcine exposure history.

The significance of non-alphagalactosyl antigens remains unclear in pig-to-primate xenotransplantation. Hanganutziu-Deicher (H-D) antigens with terminal N-glycolylneuraminic acid (NeuGc) are widely expressed on endothelial cells of mammalian species, with the exception of humans. As baboons and monkeys also express H-D antigens, a pig-to-non-human primate experimental model cannot resolve the question of whether H-D antigens can elicit a potent humoral response in human recipients. The purpose of this study was to elucidate the clinical significance of H-D antigens by examining the sera from patients who have been previously exposed to porcine tissue. After the digestion of porcine aortic endothelial cells (PAEC) by neuraminidase, NeuGc and N-acetylneuraminic acid (NeuAc) were quantitated by HPLC. IgG and IgM antibody levels against H-D antigens were measured by NeuGc-GM3-coated ELISA plates in the sera of patients who had undergone ex vivo kidney perfusion 1 to 3 weeks and 2 years previously (n=2) or had been injected with fetal porcine islets 2 months previously (n= 10). HPLC determined that 9.7x 10(7) NeuAc and 6.3x 10(7) NeuGc residues per cell were released from PAEC by neuraminidase, while 25.7x 10(7) NeuAc and an undetectable level of NeuGc were released from human aortic endothelial cells (HAEC). No significant elevation of IgG or IgM antibody levels against NeuGc-GM3 was observed in sera from patients with a history of porcine exposure. Considering the active production of antibody against the foreign galactosyl antigens after pig-to-human xenotransplantation, some production of antibodies against the equally foreign H-D antigens would be expected, because large amounts of NeuGc terminated saccharides are present in the pig endothelial cell surface. However, no production of antibodies directed to H-D antigens could be found in patients exposed to porcine tissue. Further studies are warranted to explain why H-D antigens do not elicit a significant antibody production.

Animals↗

Involvement of nitric oxide in the modulation of dural arterial blood flow in the rat.

1. Nitric oxide (NO) has been proposed to be a key molecule in the pathogenesis of migraine pain and other headaches that are linked to vascular disorders. Several lines of evidence indicate that the meningeal vascularization is crucially involved in the generation of these headaches. In an experimental model in the rat a dominating role of calcitonin gene-related peptide (CGRP) in causing neurogenic vasodilatation and increased blood flow has been shown. The aim of the present study was to clarify the role of NO in this model with regard to the meningeal blood flow. 2. The blood flow in and around the medial meningeal artery (dural arterial flow) was recorded in the exposed parietal dura mater encephali of barbiturate anaesthetized rats using laser Doppler flowmetry. Local electrical stimulation of the dura mater (pulses of 0.5 ms delivered at 7.5 - 17.5 V and 5 or 10 Hz for 30 s) caused temporary increases in dural arterial flow for about 1 min that reached peaks of 1.6 - 2.6 times the basal flow. The effects of NO synthase (NOS) inhibitors on the basal flow and the electrically evoked increases in flow were examined. 3. Systemic (i. v.) administration of N(omega)-nitro-L-arginine methyl ester (L-NAME) at cumulative doses of 10 and 50 mg kg(-1) lowered the basal flow to 87 and 72%, respectively, of the control and reduced the evoked increases in blood flow to 82 and 44% on an average. Both these effects could partly be reversed by 300 mg kg(-1) L-arginine. The systemic arterial pressure was increased by L-NAME at both doses. Injection of the stereoisomer D-NAME at same doses did not change basal flow and evoked increases in flow. 4. 4. Topical application of L-NAME (10(-4) - 10(-2) M) was effective only at the highest concentration, which caused lowering of the basal blood flow to 78% of the control; the evoked increases in flow were not changed. Topical application of 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (AMT), a specific inhibitor of the inducible NOS, at concentrations of 10(-4) - 10(-2) M lowered the basal flow to 89, 87.5 and 85%, respectively, but did not significantly change the evoked flow increases. Same concentrations of 7-nitroindazole monosodium salt (7-NINA), a specific inhibitor of the neuronal NOS, had no significant effects on basal flow and evoked increases in flow. 5. It is concluded that NO is involved in the maintenance of the basal level of dural arterial blood flow as well as in the electrically evoked flow increases, which have been shown to be mainly mediated by CGRP released from dural afferent fibres. The most important source of NO is probably the endothelium of dural arterial vessels. The synergistic effect of NO and CGRP on the stimulated blood flow may be in part due to a NO mediated facilitation of the CGRP release.

Animals↗

Procaspase 3/p21 complex formation to resist fas-mediated cell death is initiated as a result of the phosphorylation of p21 by protein kinase A.

Caspase 3 is an essential factor for Fas-mediated cell death and exists endogenously in cells where its activation is suppressed by p21 and ILP. Inside the cell, procaspase 3 interacts with p21 on mitochondria. In the present study, we investigated the molecular basis for procaspase 3/p21 complex formation. During Fas-mediated cell death, mitochondria are damaged, accompanied by decreased mitochondrial membrane-potential and decreased intracellular ATP levels. This mitochondrial damage occurs before an estrangement of the procaspase 3/p21 complex, and we demonstrate that intracellular ATP-deprivation also initiates an estrangement of procaspase 3/p21 complex formation and accelerates Fas-mediated cell death. In addition, our current results revealed that the phosphorylated p21 by PKA interacts with procaspase 3. Here, we report that the mitochondrial role, especially for ATP synthesis, and PKA are necessary for the procaspase 3/p21 complex formation to resist Fas-mediated cell death.

Adenosine Triphosphate↗

Evaluation of the PhysioFlex closed-circuit anaesthesia machine.

The concentrations of nitrous oxide, sevoflurane and oxygen in the circle system of a closed-circuit anaesthesia machine, the PhysioFlex, were measured in seven patients. During anaesthesia, the settings for each gas were changed and their concentrations recorded. At the induction of anaesthesia, it took 80-510s (median 190s) for the end-tidal sevoflurane concentration to reach 2.0%, and 920-2640s (median 1500s) for the oxygen in the breathing circuit to reach 30%. At this time, the nitrous oxide concentration was 60+/-3% (mean+/-SD). During anaesthesia, it took 90-480s (median 140s) for the end-tidal sevoflurane concentration setting to decrease from 3.0 to 1.0%, and 90-400s (median 110s) to return from 1.0 to 3.0%. When the inspired oxygen was increased from 30 to 50%, circuit concentrations reached equilibrium in 40-60s (median 40s), and when decreased from 50% back to 30%, equilibrium took 310-470s (median 450s). During recovery from anaesthesia, inspiratory sevoflurane concentration took 40-70s (median 50s) to decrease to 0.2%. The PhysioFlex provided adequate control of sevoflurane and oxygen concentrations, but not of increasing nitrous oxide concentrations.

Adult↗

Novel polysialogangliosides of skate brain structural determination of tetra, penta and hexasialogangliosides with a NeuAc-GalNAc linkage.

The gangliosides in the brain of a cartilaginous fish, skate (Bathyraja smirnovi), have been isolated and characterized by means of methylation analysis, antibody binding, enzymatic hydrolysis and MALDI-TOF MS. In addition to gangliosides with known structures (GM2, fucosyl-GM1, GD3, GD2, GT3 and GT2), five polysialogangliosides were isolated and characterized as having the following structures. (1) IV3NeuAc, III6NeuAc, II3NeuAc-Gg4Cer; (2) IV3NeuAc2, III6NeuAc, II3NeuAc-Gg4Cer; (3) IV3NeuAc, III6NeuAc, II3NeuAc2-Gg4Cer; (4) IV3NeuAc, III6NeuAc, II3NeuAc3-Gg4Cer; and (5) IV3NeuAc2, III6NeuAc, II3NeuAc3-Gg4Cer. These structures are 'hybrid-type' which comprise combinations of alpha-series and either a, b or c-series structures. Three gangliosides (2), (4) and (5), were novel. The main features of the ganglioside composition of skate brain were an abundance of gangliotriaosyl species, a lack of gangliotetraosyl species (except fucosyl-GM1), and an abundance of hybrid-types. These characteristics closely resemble those in shark brain which we reported previously [Nakamura, K., Tamai, Y. & Kasama, T. (1997) Neurochem. Int. 30, 593-604]. Two of the hybrid-type gangliosides (1) and (4), were examined for their neuritogenic activity toward cultured neuronal cells (Neuro-2A), and were found to have more potent activity than nonhybrid-type gangliosides such as GM1.

Acetylgalactosamine↗

Cell death induction by CTL: perforin/granzyme B system dominantly acts for cell death induction in human hepatocellular carcinoma cells.

Cell death induction by cytotoxic T lymphocytes (CTLs) is an important thesis for the understanding of tumor immunotherapy. In the current study we investigated the molecular machinery of CTL-induced cell death in human hepatocellular carcinoma cell lines (HCC lines). CTLs prepared from human peripheral blood induced cell death in all tested HCC lines. As the CTL-induced death system, the effectiveness of Fas ligand/Fas and/or Perforin/Granzyme B systems has been suggested, whereas cell death induction by CTLs was shown independently on Fas expression in the current study. Using various tetrapeptide inhibitors for caspase and its associated factor, we additionally demonstrated that inhibitors for caspase 3 (Ac-DEVD-CHO) and caspase 8/granzyme B (Ac-IETD-CHO) suppressed CTL-induced cell death, but an inhibitor for Fas-activated serine proteinase, which acts for the caspase 3 activator, did not, suggesting that CTL-induced cell death was initiated by the Perforin/Granzyme B system, rather than the Fas ligand/Fas system. On the basis of our current results, we report here that the Perforin/Granzyme B system acts dominantly for the cell death induction of HCC lines.

Animals↗

Long-term improvement of idiopathic hypertrophic cranial pachymeningitis by lymphocytapheresis.

We report on a 48-year-old man with idiopathic hypertrophic cranial pachymeningitis (IHCP) manifesting headache, facial pain, and tongue pain with unilateral atrophy, dysarthria, and dysphagia. Although steroid therapy ameliorated these symptoms, they recurred after he developed steroid-induced diabetes mellitus. We treated the patient by lymphocytapheresis (LCP), which resulted in an improvement of his symptoms, a reduction in the CD4 lymphocyte population, a reduction of the CD4/CD8 ratio, and a reduced thickening of the dura mater that lasted for more than 14 months. Results presented here suggest that LCP can be effective in the treatment of IHCP.

CD4-CD8 Ratio↗

Survivin promotes cell proliferation in human hepatocellular carcinoma.

Survivin is a recently described inhibitor of apoptosis. Because suppression of apoptosis is important for carcinogenesis and tumor growth, we investigated the expression and function of survivin in human hepatocellular carcinomas (HCCs). We have shown that 4 HCC cell lines and 7 out of 8 human HCC tissues expressed survivin messenger RNA (mRNA), whereas expression of survivin mRNA was not detected in normal liver and nontumor areas of these tissues using the reverse transcription polymerase chain reaction. Survivin was detected primarily in the nucleus by immunofluorescence staining of HCC cells. In addition, 14 of 20 (70%) HCC tissues showed positive nuclear staining for survivin, whereas nontumor tissues showed little detectable staining by immunohistochemistry. Survivin expression strongly correlated with the proliferation index but not significantly with the apoptosis index in HCC tissues. Therefore, we performed cell cycle analysis after survivin transfection and showed that overexpression of survivin resulted in a decrease in the G(0)/G(1) phase and an increase in the S phase in all 4 HCC cell lines. Furthermore, we have found that survivin interacted with cyclin-dependent kinase 4 (Cdk4) and overexpression of survivin released p21(WAF1/Cip1) (p21) from Cdk4. From these results, we conclude that survivin promotes cell proliferation by interacting with Cdk4 and releasing p21 from Cdk4. This may play an important role in carcinogenesis and progression of human HCCs.

Apoptosis↗

Chemotherapeutic agents augment TRAIL-induced apoptosis in human hepatocellular carcinoma cell lines.

TNF-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in various transformed cell lines but not in almost-normal tissues. It is regulated by 2 death receptors, TRAIL receptor 1 (TRAIL-R1) and TRAIL-R2, and 2 decoy receptors, TRAIL-R3 and TRAIL-R4. We investigated the expression of TRAIL-R- and TRAIL-induced apoptosis in human hepatocellular carcinomas (HCCs). TRAIL-R1, -R2, and -R4 were expressed in 6 HCC cell lines examined, but TRAIL-R3 was expressed in only 2 of the 6 cell lines. In addition, immunohistochemical results revealed a high and prevalent expression of TRAIL-R1 and -R2 in human HCC tissues. Despite the expression of TRAIL-R1 and -R2, all 6 HCC cell lines showed resistance to TRAIL-induced apoptosis with no relation to nuclear factor kappa B (NF-kappaB) levels induced by TRAIL. TRAIL-induced death signal was inhibited with both decreased caspase-8 and caspase-3 activity. However, TRAIL induced significant apoptosis in the presence of a subtoxic level of actinomycin D, indicating that the TRAIL-induced apoptotic pathway is in place in these cell lines. In addition, we found that treatment with conventional chemotherapeutic agents, doxorubicin and camptothecin, dramatically augmented TRAIL-induced cytotoxicity in most of the HCC cell lines. Actinomycin D and camptothecin almost completely suppressed NF-kappaB induction by TRAIL, whereas doxorubicin had little effect. These results indicate that TRAIL, in combination with chemotherapeutic agents, may have therapeutic potential in the treatment of human HCC.

Antibiotics, Antineoplastic↗

Effect of bilirubin UDP glucuronosyltransferase 1 gene TATA box genotypes on serum bilirubin concentrations in chronic liver injuries.

TATA box abnormality in the promoter region of the bilirubin UDP glucuronosyltransferase 1 gene has been reported to cause Gilbert's syndrome in white subjects. It has also been reported that the majority of Japanese patients with Gilbert's syndrome are heterozygous for Gly71Arg in the coding region of this gene. On the other hand, some patients with chronic hepatitis often show signs of unexpected hyperbilirubinemia. The aims of this study were to determine which of the genetic variations, TATA box genotype or codon 71 genotype, is most closely related to serum bilirubin concentrations, and whether the TATA box genotype has an effect on serum bilirubin concentrations in patients with hepatitis C-associated chronic liver diseases. In a sample of 300 individuals selected from among the general Japanese population, mean concentrations of total serum bilirubin differed significantly among TATA box genotypes, but not among codon 71 genotypes. Concentration of total serum bilirubin was significantly correlated with TATA box genotypes. In 211 patients with hepatitis C-associated chronic liver diseases, mean concentrations of total serum bilirubin also differed significantly among TATA box genotypes. In patients with chronic hepatitis C, concentration of total serum bilirubin was significantly correlated with TATA box genotypes. In summary, TATA box genotypes, but not codon 71 genotypes, are closely related to serum bilirubin concentrations. TATA box genotypes should therefore be considered when evaluating hepatic function by serum bilirubin concentrations in cases of hepatitis C-associated chronic liver diseases.

Adult↗

Hepatocyte growth factor promotes cell survival from fas-mediated cell death in hepatocellular carcinoma cells via Akt activation and Fas-death-inducing signaling complex suppression.

The Akt/PI-3 kinase pathway is a system essential for cell survival. In the current study, we showed that hepatocyte growth factor (HGF) activates the Akt/PI-3 kinase pathway to suppress Fas-mediated cell death in human hepatocellular carcinoma (HCC; 3 lines; SK-Hep1, HLE, and Chang Liver cell lines), hepatoblastoma (1 line; HepG2), and embryonic hepatocyte (1 line; WRL). Five tested cell lines showed the resistance to Fas-mediated cell death by the pretreatment of HGF. This HGF-induced cell survival was suppressed by wortmannin (Akt/PI-3 kinase pathway inhibitor), suggesting an involvement of Akt. When cells were pretreated with HGF, Fas-mediated cell death was suppressed, followed by Akt phosphorylation at Ser473. Fas-death-inducing signaling complex (DISC) formation, especially FADD and caspase 8 interaction, was suppressed by HGF and the suppression of the Akt/PI-3 kinase pathway by transient expression of PTEN, resulting in acquisition of Fas-DISC formation and Fas-mediated cell death in HGF-treated cells. We suggest that HGF promotes cell survival in hepatocyte-derived cell lines (HCC, hepatoblastoma, and embryonic hepatocyte) from Fas-mediated cell death via Fas-DISC suppression as a result of Akt activation.

Carcinoma, Hepatocellular↗

Flow-cytometric separation and enrichment of hepatic progenitor cells in the developing mouse liver.

Stem cells responsible for tissue maintenance and repair are found in a number of organs. However, hepatic stem cells assumed to play a key role in liver development and regeneration remain to be well characterized. To address this issue, we set up a culture system in which primitive hepatic progenitor cells formed colonies. By combining this culture system with fluorescence-activated cell sorting (FACS), cells forming colonies containing distinct hepatocytes and cholangiocytes were identified in the fetal mouse liver. These cells express both CD49f and CD29 (alpha6 and beta1 integrin subunits), but do not mark for hematopoietic antigens such as CD45, TER119, and c-Kit. When transplanted into the spleen, these cells migrated to the recipient liver and differentiated into liver parenchymal cells. Our data demonstrate that hepatic progenitor cells are enriched by FACS and suggest approaches to supplanting organ allografting and improving artificial-organ hepatic support.

Animals↗

Evaluation of the modified maxillary protractor applied to Class III malocclusion with retruded maxilla in early mixed dentition.

The purpose of this study was to evaluate the effects of orthodontic treatment with a maxillary protraction bow appliance on anterior crossbite patients with Class III malocclusion in the mixed dentition. The 29 patients treated with a maxillary protraction bow appliance (11 boys, 18 girls) were compared with 25 matched, untreated controls with anterior crossbite (10 boys, 15 girls). The mean age before treatment was 8 years 7 months (range, 6 years 3 months to 11 years 6 months). The mean treatment period to achieve a normal overjet was 10.2 months (range, 5 to 18 months). Fifty-nine cephalometric angular and linear parameters were compared between the treated group and the untreated controls using the analysis of variance and the paired t test to evaluate the effect of gender and the maxillary protraction bow appliance treatment. Skeletal and dentoalveolar advancement of the maxilla and retrusion of the mandible contributed significantly to the improvement of Class III malocclusion in the treated group. These results suggest that a maxillary protraction bow appliance is effective for correcting anterior crossbite with a retruded maxilla in the early mixed dentition.

Cephalometry↗

Fas/Fas ligand expression and characteristics of primed CD45RO+ T cells in the inflamed mucosa of ulcerative colitis.

BACKGROUND: Chronic immune activation in the colon is characteristic of ulcerative colitis (UC). Fas/Fas ligand (FasL) system is a mechanism responsible for activation-induced cell death (AICD), which maintains homeostasis within the immune system. Thus, Fas/FasL expression on activated colonic T cells of UC patients, as well as the susceptibility of such T cells to AICD was investigated in order to determine the role of activated colonic T cells in the long lasting inflammation in UC. METHODS: Fas, FasL, and CD45RO expression on peripheral blood and colonic T cells of UC patients were assayed by flow cytometry. Apoptosis of colonic T cells induced by anti Fas antibody was assessed using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay. RESULTS: The majority of colonic T cells expressed both CD45RO and Fas in the colonic mucosa, a situation that was quite different from that in the peripheral blood. The number of CD45RO+CD8+ and Fas+CD8+ T cells was significantly lower in UC patients than the controls, unlike the number of Fas+CD4+ T cells. In contrast, the number of both CD45RO+CD4+ and CD45RO+CD8+ T cells in UC mucosa expressing FasL was significantly higher than in the controls. While Fas mediated apoptosis of CD45RO+CD8+ T cells was higher in UC patients than the controls, the number of apoptotic CD45RO+CD4+ T cells from UC mucosa was not. CONCLUSIONS: In UC patients, CD45RO+CD4+ T cells are less sensitive to apoptotic signals mediated by Fas. These phenomena may contribute to the pathogenesis of UC.

Adult↗