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Biomedical subjects

H Wakabayashi

Publications and source records attributed to H Wakabayashi.

At least 19 recordsLinked to original sources
PubMed1999

Novel proteoglycan linkage tetrasaccharides of human urinary soluble thrombomodulin, SO4-3GlcAbeta1-3Galbeta1-3(+/-Siaalpha2-6)Galbeta1-4Xyl.

O-linked sugar chains with xylose as a reducing end linked to human urinary soluble thrombomodulin were studied. Sugar chains were liberated by hydrazinolysis followed by N-acetylation and tagged with 2-aminopyridine. Two fractions containing pyridylaminated Xyl as a reducing end were collected. Their structures were determined by partial acid hydrolysis, two-dimensional sugar mapping combined with exoglycosidase digestions, methylation analysis, mass spectrometry, and NMR as SO4-3GlcAbeta1-3Galbeta1-3(+/-Siaalpha2-6)Galbeta1+ ++-4Xyl. These sugar chains could bind to an HNK-1 monoclonal antibody. This is believed to be the first example of a proteoglycan linkage tetrasaccharide with glucuronic acid 3-sulfate and sialic acid.

Binding Sites, Antibody↗
PubMed1999

Microsomal cytochrome P-450 monooxygenase system and its drug-metabolizing activity after partial portal vein ligation in the Rat.

Percutaneous transhepatic portal vein embolization (PTPE) has been used to decrease the risk of hepatic failure after hepatectomy in patients with poor liver function. The effect of PTPE on hepatic drug-metabolizing activities is not clear. Therefore we examined the effect of portal vein branch ligation, a model of PTPE, on hepatic drug-metabolizing activities in Sprague-Dawley rats. Ligated and nonligated lobes were harvested separately. Drug-metabolizing activities and concentrations of components of the microsomal cytochrome P-450 monooxygenase system were examined. In ligated lobes, drug-metabolizing activities (lidocaine and aminopyrine) and enzymatic concentrations of the microsomal cytochrome P-450 monooxygenase system gradually decreased over 10 days. In nonligated lobes these functions were depressed rapidly to 60% of those before PBL but then recovered 10 days after PBL. From the viewpoint of drug metabolism, hepatic dysfunction occurred in both ligated and nonligated lobes.

Aminopyrine↗
PubMed1999

Experimental study of the effect of intraportal prostaglandin E1 on hepatic blood flow during reperfusion after ischaemia and hepatectomy.

BACKGROUND: Prostaglandin E1 (PGE1) has protective effects experimentally and clinically in individual models of hepatic ischaemia-reperfusion injury and of partial hepatectomy. The present study investigated the effects of intraportal administration of PGE1 on hepatic blood flow, systemic arterial pressure and long-term animal survival after 60 min of total liver ischaemia followed by 70 per cent partial hepatectomy in rats. METHODS: Total liver ischaemia was induced by occluding the hepatoduodenal ligament for 60 min. PGE1 0.5 microg per kg per min was infused intraportally for 15 min before inducing ischaemia and for 120 min after ischaemia in the treatment group. Normal saline was infused in the control group. During ischaemia 70 per cent partial hepatectomy was performed. Portal venous flow (PVF), peripheral tissue blood flow (PTBF) and hepatic artery flow were measured before and after ischaemia. Serum biochemical analysis was carried out at 1, 3 and 24 h, and 7 and 14 days; and liver histology at 1 and 24 h, and 7 days after reperfusion. Survival was followed for 1 year. RESULTS: Intraportal infusion of PGE1 significantly improved PVF and PTBF without affecting the systemic arterial pressure. Long-term survival was significantly higher in the PGE1 group. Serum aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase levels decreased significantly, and 2-h bile flow was significantly improved, in the PGE1 group. Histological examination revealed significant portal venous congestion, sinusoidal congestion, fatty degeneration and tissue necrosis 24 h and 7 days after reperfusion in the control group. CONCLUSION: PGE1 has a protective effect against liver damage when the liver is injured by warm ischaemia and reperfusion followed by partial resection.

Alprostadil↗
PubMed1999

Increased levels of epsilon and gamma isoforms of 14-3-3 proteins in cerebrospinal fluid in patients with Creutzfeldt-Jakob disease.

We established four hybridoma cell lines producing monoclonal antibodies (MAbs) against 14-3-3 proteins. Immunoblot analysis revealed that epsilon and gamma isoforms were specifically increased in premortem cerebrospinal fluid samples from patients with sporadic Creutzfeldt-Jakob disease. Furthermore, dot immunoblot analysis showed that MAbs were more specific for native antigen than polyclonal antibodies were.

14-3-3 Proteins↗
PubMed1999

Inhibition of iron/ascorbate-induced lipid peroxidation by an N-terminal peptide of bovine lactoferrin and its acylated derivatives.

Bovine lactoferrin (LF) and lactoferricin B (LFcin B), an antimicrobial peptide derived from bovine LF, inhibited thiobarbituric acid-reactive substance (TBARS) formation in a iron/ascorbate-induced liposomal phospholipid peroxidation system. The inhibition of TBARS formation occurred with N-acylated 9-mer peptides with a core sequence of LFcin B and, compared to LFcin B, their antioxidant effect was clearly observed at a concentration almost 100 times lower.

Acylation↗
PubMed1999

Gene therapy of chondrosarcoma using retrovirus vectors encoding the herpes simplex virus thymidine kinase gene.

Human chondrosarcoma cells (HCS-TG) were transduced with the gene for a herpes simplex virus thymidine kinase (HSV-tk) or Escherichia coli beta-galactosidase (lacZ). We investigated the cytotoxicity of human chondrosarcoma bearing an HSV-tk gene after treatment with ganciclovir. Chondrosarcoma cells bearing an HSV-tk gene were more sensitive than non-transduced cells. Coculturing with chondrosarcoma cells bearing both an HSV-tk gene (HCS-TG-tk) and lacZ gene (HCS-TG-Z) in various ratios showed a bystander effect. Chondrosarcoma implanted in nude mice were injected with HCS-TG-tk cells. After 4 weeks, the growth of tumors was significantly prevented.

Animals↗
PubMed1998

Endothelin-1-(1-31), a novel vasoactive peptide, increases [Ca2+]i in human coronary artery smooth muscle cells.

We have previously found that human chymase cleaves big endothelins at the Tyr31-Gly32 bond and produces 31-amino acid long endothelins-(1-31), without any further degradation products. In this study, we investigated the effect of synthetic endothelin-1-(1-31) on the intracellular free Ca2+ concentration ([Ca2+]i) in cultured human coronary artery smooth muscle cells. Endothelin-1-(1-31) increased [Ca2+]i in a concentration-dependent manner (10(-14) to 10(-10) M). This endothelin-1-(1-31)-induced [Ca2+]i increase was not affected by phosphoramidon (N-(alpha-Rhamnopyranosyloxyhydroxyphosphinyl)-L-Leucyl-L-Tryptoph an), an inhibitor of endothelin-converting enzyme. It was, however, inhibited by 10(-10) M BQ123 (Cyclo-(-D-Trp-D-Asp(ONa)-Pro-D-Val-Leu-)), an endothelin ET(A) receptor antagonist, but not by 10(-10) M BQ788 (N-cis-2,6-dimethylpiperidinocarbonyl-L-yMeLeu-D-Trp(COOM e)-D-Nle-ONa), an endothelin ET(B) receptor antagonist. These results suggest that endothelin-1-(1-31) by itself exhibits vasoactive properties probably through endothelin ET(A) receptors. Since human chymase has been reported to play a role in atherosclerosis, endothelin-1-(1-31) may be one of the candidate substances for its cause.

Calcium↗
PubMed1998

New ferromagnetic bone cement for local hyperthermia.

We have developed a ferromagnetic bone cement as a thermoseed to generate heat by hysteresis loss under an alternate magnetic field. This material resembles bioactive bone cement in composition, with a portion of the bioactive glass ceramic component replaced by magnetite (Fe3O4) powder. The temperature of this thermoseed rises in proportion to the weight ratio of magnetite powder, the volume of the thermoseed, and the intensity of the magnetic field. The heat-generating ability of this thermoseed implanted into rabbit and human cadaver tibiae was investigated by applying a magnetic field with a maximum of 300 Oe and 100 kHz. In this system, it is very easy to increase the temperature of the thermoseed in bone beyond 50 degrees C by adjusting the above-mentioned control factors. When the temperature of the thermoseed in rabbit tibiae was maintained at 50 to 60 degrees C, the temperature at the interface between the bone and muscle (cortical surface) surrounding the material rose to 43 to 45 degrees C; but at a 10-mm distance from the thermoseed in the medullary canal, the temperature did not exceed 40 degrees C. These results demonstrate that ferromagnetic bone cement may be applicable for the hyperthermic treatment of bone tumors.

Animals↗
PubMed1998

Enhanced anti-Candida activity of neutrophils and azole antifungal agents in the presence of lactoferrin-related compounds.

We investigated the effects of lactoferrin (Lf)-related compounds on growth inhibition of Candida albicans by neutrophils or antifungal agents in vitro. Human neutrophils partially inhibited the growth of C.albicans. The growth inhibition caused by human neutrophils was augmented by the addition of human Lf at concentrations which did not show any inhibitory effect in the absence of neutrophils. Similar observations were obtained also with the following combinations: human neutrophils + bovine Lf, murine neutrophils + bovine Lf, and murine neutrophils + iron saturated bovine Lf, but not in the case of murine neutrophils + human transferrin. The minimum inhibitory concentration (MIC) of azole antifungal agents, clotrimazole, ketoconazole, fluconazole, and itraconazole was reduced by 1/4 to 1/16 in the presence of a sub-MIC level of each of bovine Lf, bovine Lf pepsin hydrolysate, and the antimicrobial peptide "lactoferricin B" (Lfcin B). Other types of antifungal agents, amphotericin B, nystatin, and flucytosine did not show such combined effects with these Lf-related compounds. The anti-Candida activity of bovine Lf or Lfcin B in combination with clotrimazole was shown to be synergistic by checkerboard analysis. Clinically isolated azole-resistant C. albicans strains were more susceptible to bovine Lf or Lfcin B than azole-susceptible strains. Trailing growth of an azole-resistant strain in the presence of fluconazole was reduced by the addition of sub-MIC levels of bovine Lf or Lfcin B. These results suggest that Lf-related compounds even at relatively low concentrations may function as an antifungal effector in combination with neutrophils thereby modulating azole antifungal efficacies in vivo.

Animals↗
PubMed1998

Effects of orally administered bovine lactoferrin on the immune system of healthy volunteers.

A protective effect of bovine lactoferrin (Lf) during lethal bacteraemia has been reported in mice. Also, protective effects of orally administered bovine Lf have been reported in cases of intractable stomatitis in cats and Cryptocaryon irritans infection in red sea bream. In this study, we examined the effects of orally administered bovine Lf on the immune system of healthy volunteers. Ten healthy male volunteers (age range of 31 to 55 years old) were given bovine Lf (2 g/body/day) for 4 weeks. Blood samples were drawn before, during and after administration of Lf. Phagocytic activity and superoxide production activity of polymorphonuclear leukocytes (PMN) were evaluated from the number of PMN phagocytizing polymer particles and by the dichlorofluorescein (DCFH) oxidation assay, respectively. The expression levels of CD11b, CD16 and CD56 molecules on leukocytes were quantified using flow cytometry. The phagocytic activity of PMN increased during the period of Lf administration in 3 of the 10 volunteers. In 2 of the 3 volunteers in which the phagocytic activity increased, PMN expressed CD16 at higher levels corresponding to the increase in 3 of the 10 volunteers, whereas the CD11b+ lymphocytes and CD56+ lymphocytes increased in 4 volunteers including the same 3 volunteers who showed an increase in CD16+. These results suggest that the proportion of natural killer (NK) cells among the lymphocytes might have increased in these subjects. It was demonstrated that the phagocytic activity or superoxide production activity of PMN or the proportions of CD11b+, CD16+ and CD56+ in lymphocytes was influenced by Lf administration in 7 of the 10 volunteers, while the effects of Lf on the immune system differed in individual cases. These results suggest that Lf administration may influence primary activation of the host defense system.

Administration, Oral↗
PubMed1998

The role of glutamate in the locus coeruleus during opioid withdrawal and effects of H-7, a protein kinase inhibitor, on the action of glutamate in rats.

To investigate the role of glutamate in the locus coeruleus (LC) during opioid withdrawal, rats were continuously infused with morphine (a mu-opioid receptor agonist, 26 nmol/microl/h) or butorphanol (a mu/delta/kappa-mixed opioid receptor agonist, 26 nmol/microl/h) intracerebroventricularly (i.c.v.) via osmotic minipumps for 3 days. A direct LC injection of glutamate (1 or 10 nmol/5 microl) or naloxone (an opioid receptor antagonist, 24 nmol/5 microl) induced withdrawal signs in morphine- or butorphanol-dependent animals. However, these agents failed to precipitate any withdrawal signs in saline-treated control animals. On the other hand, the expression of withdrawal signs precipitated by the administration of glutamate or naloxone in opioid-dependent animals was completely blocked by concomitant infusion with 1 or 10 nmol/microl/h of an inhibitor of adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase and protein kinase C, H-7 [1-(5-isoquinolinesulfonyl)-2-methylpiperazine]. In animals that had been infused with opioids in the same manner, i.c.v. injection of naloxone (48 nmol/5 microl) precipitated withdrawal signs and increased extracellular fluid levels of glutamate in the LC of morphine- or butorphanol-dependent rats measured by in vivo microdialysis method. However, concomitant infusion with H-7 inhibited the increases of glutamate levels in the LC. These results strongly suggest that an expeditious release of glutamate in the LC region plays an important role in the expression of physical dependence on opioids. Furthermore, the action on glutamate release might be increased by the enhancement of cAMP-dependent protein kinase and/or protein kinase C activity.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1998

Morphological and functional alterations to sinusoidal endothelial cells in the early phase of endotoxin-induced liver failure after partial hepatectomy in rats.

Liver failure following major hepatectomy is characterized pathologically by massive hepatic necrosis, which is thought to begin with injury of sinusoidal endothelial cells (SECs). To examine the early events of SECs leading to hepatic damage, we performed time-course analyses of the morphological and functional perturbation of SECs after endotoxin administration to hepatectomized rats. At 1.5 h after endotoxin injection, when hepatocellular damage was not yet evident, SECs showed augmented expression of intercellular adhesion molecule-1, with frequent adherence of infiltrating leucocytes and ultrastructural features of defenestration and hypertrophied cytoplasm enriched with cell organelles. The serum level of hyaluronate, as an indicator of the functional state of SECs, was significantly elevated. At 3 h, SECs underwent necrosis and disruption, accompanied by fibrin deposits with concomitant hepatocellular necrosis. The morphological and functional alterations of SECs precede necrotic changes in hepatocytes and SECs in endotoxin-induced liver failure after partial hepatectomy.

Animals↗
PubMed1998

Liver bilirubin UDP-glucuronosyltransferase activity in chronic nonhemolytic unconjugated hyperbilirubinemia of adults.

Ten adult patients with chronic nonhemolytic unconjugated (indirect) hyperbilirubinemia were analyzed by determining bilirubin uridine diphosphate-glucuronosyltransferase activity according to a more physiological and sensitive method (9 control cases, 0.457 +/- 0.163 nmole/mg protein/min). There was no overlap of the enzyme activities of 2 cases with Crigler-Najjar syndrome (type II) (0.006 nmole/mg protein/min on average) and 6 cases with Gilbert's syndrome (0.051 +/- 0.016 nmole/mg protein/min). The enzyme activities in 2 patients with post-hepatitic hyperbilirubinemia were within the normal range. A new classification of nonhemolytic unconjugated hyperbilirubinemia in adults is proposed according to the results of this enzyme activity and the recent data on the gene mutation of this enzyme.

Adolescent↗
PubMed1998

Modified hepatoduodenal ligamentectomy for advanced carcinoma of the biliary tract: the importance of preservation of the replaced left hepatic artery.

Hepatoduodenal ligamentectomy (ligamentectomy) is the ultimate surgery for biliary tract carcinoma involving perioperative difficulties such as total hepatic ischemia during revascularization of the hepatic artery and the portal vein, patency of the reconstructed hepatic artery, and high incidence of related operative mortality. In the present study, modified ligamentectomies with extended right hepatic lobectomy, including resection of the caudate lobe, were performed on three patients with advanced biliary tract carcinoma in whom the left hepatic artery had been replaced and the original artery was preserved. In all patients, postoperative courses were uneventful: success of the resection was confirmed by histological examination. This procedure enabled en bloc resection of hepatoduodenal ligament with positive cancer invasion to take place. It was carried out safely without concern for the difficulties described above. In our view, ligamentectomy should be performed in all such cases.

Aged↗
PubMed1998

Treatment of recurrent hepatocellular carcinoma by hepatectomy with right and middle hepatic vein reconstruction using total vascular exclusion with extracorporeal bypass and hypothermic hepatic perfusion: report of a case.

We report herein the case of a patient who had previously undergone a lateral segmentectomy for hepatocellular carcinoma (HCC) in whom recurrent HCC invading the trunk of the right and middle hepatic veins in a damaged liver was treated by reconstruction of both hepatic veins, using total vascular exclusion with extracorporeal bypass and hypothermic hepatic perfusion. Reconstruction was performed using a graft taken from the left external iliac vein and divided into two pieces. Hepatic ischemia lasted for 91 min during the procedure and the intrahepatic temperature, as monitored by inserting a needle-type thermometer, was decreased to 11 degrees C throughout the procedure. The peak levels of serum glutamic pyruvic transaminase, lactate dehydrogenase, and total bilirubin were 363 IU/l, 1198 IU/ml, and 2.8 mg/dl, respectively, on postoperative day (POD) 2. The patient's postoperative course was uneventful except for mild, temporary swelling of the left leg. Postoperative computed tomography and magnetic resonance imaging examinations disclosed no obstruction of either graft, and the patient was discharged on POD 40.

Carcinoma, Hepatocellular↗
PubMed1998

Effect of Helicobacter pylori infection on gastric mucosal phospholipid contents and their fatty acid composition.

To investigate the effect of Helicobacter pylori infection on the 'gastric mucosal barrier', phospholipid contents and the fatty acid composition of endoscopic biopsy specimens of the gastric mucosa were analysed in healthy volunteers with and without H. pylori infection. The gastric corporeal phosphatidylcholine (PC) content of H. pylori-positive healthy volunteers was less than that of H. pylori-negative healthy volunteers (P < 0.05). Moreover, H. pylori-positive healthy volunteers had a decrease in linoleic acid composition (P < 0.0001) and an increase in arachidonic acid composition (P < 0.0001) and in the arachidonic acid/linoleic acid ratio (P < 0.0001) of antral and corporeal PC compared with H. pylori-negative healthy volunteers. These findings suggest that H. pylori infection enhances production of various eicosanoids, resulting in changes in the gastric mucosal phospholipid contents and their fatty acid composition, that may consequently cause the gastric mucosal barrier to be weakened.

Adult↗