Biomedical subjects

Hideki Abe

Publications and source records attributed to Hideki Abe.

At least 19 recordsLinked to original sources

PubMed2006

Synthetic studies toward GKK1032s, novel antibiotic antitumor agents: enantioselective synthesis of the fully elaborated tricyclic core via an intramolecular Diels-Alder cycloaddition.

An enantioselective synthesis of the fully elaborated tricyclic decahydrofluorene core (ABC-ring system) of GKK1032s, novel antimicrobial and antitumor agents, has been accomplished for the first time by employing a highly diastereoselective intramolecular Diels-Alder (IMDA) reaction. The key substrate for the IMDA reaction was efficiently prepared through (i) an intermolecular Diels-Alder reaction between a siloxydiene and an optically active enone derived from D-mannitol to construct the appropriately functionalized C-ring and (ii) CuCl-promoted Stille coupling of an (E)-vinyl iodide and a vinylstannane to install the requisite triene side chain as the crucial steps.

Antibiotics, Antineoplastic↗

PubMed2006

Thermal degradation of environmentally degradable poly(hydroxyalkanoic acid)s.

Aliphatic polyesters have attracted industrial attention as environmentally degradable thermoplastics to be used for a wide range of applications. Besides intensive studies on the biodegradability of aliphatic polyesters, understanding of the thermal stability has importance for processing, application, and recycling. The details of thermal degradation processes of five types of aliphatic polyesters; namely, poly(L-lactide), poly(3-hydroxybutyric acid), poly(4-hydroxybutyric acid), poly(delta-valerolactone), and poly(epsilon-caprolactone), were investigated by means of several thermoanalytical techniques under both isothermal and non-isothermal conditions. In this feature article, the thermal degradation behaviors of aliphatic polyesters with different numbers of carbon atoms in the main chain of the monomeric unit are reviewed. In addition, the effects of chain-end structure and residual metal compounds on the thermal degradation processes of aliphatic polyesters consisting of hydroxyalkanoic acid monomeric units are presented. Schemes of thermal degradation reaction of poly(hydroxyalkanoic acid)s.

Caproates↗

PubMed2006

Five-year survival following a medial pancreatectomy for an invasive ductal carcinoma from the body of the pancreas.

We report a rare case of a patient who survived for 5 years after undergoing a medial pancreatectomy for invasive ductal carcinoma originating from the body of the pancreas. A 63-year-old woman was diagnosed as a small cancer of the pancreatic body, and surgery was performed. Even though the tumor was a carcinoma, its small size prompted us to perform a medial pancreatectomy with regional lymph nodes dissection. Additional chemoradiation was performed and, five years after surgery, the patient is well with no signs of recurrence. Medial pancreatectomy for invasive ductal carcinoma has not ever been reported. Furthermore, long-term survival after a lumpectomy for invasive ductal carcinoma has never been reported in the literatures. The current case suggests that long-term survival in patients with invasive ductal carcinoma of the pancreas may be associated with the pathological or biological features of pancreatic carcinoma.

Carcinoma, Pancreatic Ductal↗

PubMed2006

Adsorption of biopolyester depolymerase on silicon wafer and poly[(R)-3-hydroxybutyric acid] single crystal revealed by real-time AFM.

The adsorption behavior of PHB depolymerase from R. pickettii T1 on a silicon wafer and on P(3HB) single crystals has been studied by real-time and AFM in air and a buffer solution. First, the morphology of PHB depolymerase adsorbed on a silicon wafer was characterized to show that one molecule of PHB depolymerase has dimensions of 2.2 +/- 0.7 nm height and 16 +/- 5 nm width. The observation of PHB depolymerase adsorbed on a P(3HB) single crystal indicated that the dimensions of enzyme on the crystalline surface in air were 1.2 +/- 0.5 nm high and 28 +/- 7 nm wide, while enzyme molecules with dimensions of 2.1 +/- 0.6 nm height and 16 +/- 7 nm width were detected in a buffer solution. Comparison of the dimensions of PHB depolymerase in air with those in a buffer solution showed that the enzyme was squashed in air, but not in a buffer solution. In addition, the influence of enzymatic adsorption on the molecular state of the P(3HB) crystalline surface was investigated. The AFM images of P(3HB) single crystals after enzymatic adsorption and washing with ethanol indicated that the adhesion of PHB depolymerase changed the molecular state and generated holes on the crystalline surface.

Adsorption↗

PubMed2006

Phase structure and enzymatic degradation of poly(L-lactide)/atactic poly(3-hydroxybutyrate) blends: an atomic force microscopy study.

Phase structures and enzymatic degradation of poly(l-lactide) (PLLA)/atactic poly(3-hydroxybutyrate) (ata-PHB) blends with different compositions were characterized by using atomic force microscopy (AFM). Differential scanning calorimetry (DSC) thermograms of PLLA/ata-PHB blends with different compositions showed two glass transition temperatures, indicating that the PLLA/ata-PHB blends are immiscible in the melt. Surface morphologies of the thin films for PLLA/ata-PHB blends were determined by AFM. Phase separated morphology was recognized from the AFM topography and phase images. The domain size of the components was dependent on the blend ratio. Enzymatic degradation of the PLLA/ata-PHB blends was performed by using both PHB depolymerase and proteinase K. Either PLLA or ata-PHB domains were eroded depending on the kinds of enzyme. Surface morphologies after enzymatic degradation have revealed the phase structure along the depth direction. Enzymatic adsorption of PHB depolymerase was examined on the surface of PLLA/ata-PHB blends. The enzyme molecules were found on both domains of the binary blends. The larger number of enzyme molecules was found on the PLLA domains relative to those on the ata-PHB domains, suggesting the higher affinity of the enzyme against PLLA domain.

Adsorption↗

PubMed2006

Interaction of hemoglobin vesicles, a cellular-type artificial oxygen carrier, with human plasma: effects on coagulation, kallikrein-kinin, and complement systems.

Hemoglobin vesicles (HbVs), cellular-type artificial oxygen carriers containing human hemoglobin, were assessed for their biocompatibility by mixing with human plasma in vitro. Among three kinds of HbVs (PEG-DPEA-HbV, PEG-DPPG-HbV and DPPG-HbV), PEG-DPEA-HbV did not affect the extrinsic or intrinsic coagulation activities of the plasma, while PEG-DPPG-HbV and DPPG-HbV tended to shorten the intrinsic coagulation time. The kallikrein-kinin cascade of the plasma was slightly activated by PEG-DPPG-HbV and DPPG-HbV, but not by PEG-DPEA-HbV. The complement consumption of the plasma was observed by incubation with DPPG-HbV, but not with PEG-DPEA-HbV or PEG-DPPG-HbV. These results indicate that PEG-DPEA-HbV has a higher biocompatibility with human plasma.

Blood Coagulation↗

PubMed2005

Interaction between poly[(R)-3-hydroxybutyrate] depolymerase and biodegradable polyesters evaluated by atomic force microscopy.

Adsorption of PHB depolymerase from Ralstonia pickettii T1 to biodegradable polyesters such as poly[(R)-3-hydroxybutyrate] (PHB) and poly(l-lactic acid) (PLLA) was investigated by atomic force microscopy (AFM). The substrate-binding domain (SBD) with histidines within the N-terminus was prepared and immobilized on the AFM tip surface via a self-assembled monolayer with a nitrilotriacetic acid group. Using the functionalized AFM tips, the force-distance measurements for polyesters were carried out at room temperature in a buffer solution. In the case of AFM tips with immobilized SBD and their interaction with polyesters, multiple pull-off events were frequently recognized in the retraction curves. The single rupture force was estimated at approximately 100 pN for both PLLA and PHB. The multiple pull-off events were recognized even in the presence of a surfactant, which will prevent nonspecific interactions, but reduced when using polyethylene instead of polyesters as a substrate. The present results provide that the PHB depolymerase adsorbs specifically to the surfaces of polyesters and that the single unbinding event evaluated here is mainly associated with the interaction between one molecule of SBD and the polymer surface.

Journal Article↗

PubMed2005

DNA damage by fasicularin.

Fasicularin is a structurally novel thiocyanate-containing alkaloid isolated from the ascidian Nephteis fasicularis. Early biological experiments suggested that this compound's cytotoxic properties may stem from its ability to damage cellular DNA. Sequence gel analysis reveals that treatment of a 5'-32P-labeled DNA duplex with fasicularin in pH 7.0 buffer causes strand cleavage selectively at guanine residues. Further experiments indicate that production of these base-labile lesions in DNA involves alkylation of guanine residues by a fasicularin-derived aziridinium ion. This work reveals fasicularin as the first natural product found to generate a DNA-alkylating aziridinium ion via a mechanism analogous to the clinically used anticancer drugs mechlorethamine, melphalan, and chlorambucil.

Base Sequence↗

PubMed2005

Firing pattern and rapid modulation of activity by estrogen in primate luteinizing hormone releasing hormone-1 neurons.

We have shown previously that cultured LHRH-1 neurons, derived from monkey olfactory placode region, exhibit pulsatile LHRH-1 release at hourly intervals and spontaneous intracellular calcium oscillations, which synchronize at a frequency similar to LHRH-1 release. Brief application of estrogen induced a rapid increase in the frequency of intracellular calcium oscillations and the frequency of synchronizations. The estrogen-induced frequency of intracellular calcium oscillations was mediated by estrogen receptors (ER), whereas the frequency of synchronizations was not mediated by ER. In the present study, we further examined the rapid action of estrogen using patch-clamp recording in primate LHRH-1 neurons. Cell-attached patch-clamp recording showed that LHRH-1 neurons exhibited monophasic or biphasic action currents that were sensitive to an increase in extracellular K+ and the sodium channel blocker tetrodotoxin. The majority (90%) of LHRH-1 neurons showed irregular firing patterns composed of bursts and irregular beatings of action currents, which further formed a "cluster" firing pattern. Brief application of 17beta-estradiol (1 nM) increased the firing frequency and burst duration of LHRH-1 neurons with a latency of 60-120 sec for up to 25 min. ICI182,780, an ER antagonist, blocked the 17beta-estradiol-induced increase in the firing activity of LHRH-1 neurons. These results suggest that 1) primate LHRH-1 neurons exhibit complex firing patterns composed of activities with different time domains, 2) estrogen causes rapid stimulatory action of firing activity, and 3) this estrogen action is mediated by ER in primate LHRH-1 neurons.

Animals↗

PubMed2005

Wallerian degeneration involves Rho/Rho-kinase signaling.

Local axon degeneration is a common pathological feature of many neurodegenerative diseases, whereas the underlying molecular mechanisms are largely unknown. In this study, we used the degeneration of transected axons, termed "Wallerian degeneration," as a model to examine the possible involvement of Rho. Nogo-66, a myelin-derived inhibitor of axon regeneration, significantly accelerated axon degeneration of the dorsal root ganglion explant in vitro, whereas inhibiting Rho-kinase activity abolished the effect. Rho activation was observed in the distal part of the injured axons after spinal cord injury. We demonstrate that degeneration of the injured cortico-spinal axons was significantly retarded by a Rho-kinase inhibitor in vivo. Our findings suggest that inhibiting the signaling pathway may retard axon degeneration in pathological conditions.

Amides↗

PubMed2005

Characterization and properties of G4X mutants of Ralstonia eutropha PHA synthase for poly(3-hydroxybutyrate) biosynthesis in Escherichia coli.

Modification of the type I polyhydroxyalkanoate synthase of Ralstonia eutropha (PhaC(Re)) was performed through systematic in vitro evolution in order to obtain improved PhaC(Re) having an enhanced activity of poly(3-hydroxybutyrate) (PHB) synthesis in recombinant Escherichia coli. For the first time, a beneficial G4D N-terminal mutation important for the enhancement of both PHB content in dry cells and PhaC(Re) level in vivo was identified. Site-directed saturation mutagenesis at the G4 position enabled us to identify other mutations conferring similar enhanced characteristics. In addition, the PHB homopolymer synthesized by most G4X single mutants also had higher molecular weights than that of the wild-type. In vitro enzymatic assays of purified G4D mutant PhaC(Re) revealed that the mutant enzyme exhibited slightly lower activity and reaction efficiency compared to the wild-type enzyme. [diagram in text].

Acyltransferases↗

PubMed2005

Biosynthesis of polyhydroxyalkanoate (PHA) copolymer from fructose using wild-type and laboratory-evolved PHA synthases.

Eleven laboratory-evolved polyhydroxyalkanoate (PHA) synthases which originated from Pseudomonas sp. 61-3 enzyme (PhaC1(Ps)), together with the wild-type enzyme, were applied for PHA synthesis from fructose using Ralstonia eutropha PHB(-)4 as a host strain. The evolved PhaC1(Ps) mutants had amino acid substitution(s) at position 325 and/or position 481. In these mutants, serine-325 (S325) was replaced by cysteine (C) or threonine (T), while glutamine-481 (Q481) was replaced by lysine (K), methionine (M) or arginine (R). All recombinant strains harboring the genes of the evolved PhaC1(Ps) mutants produced a significantly increased amount of PHA (55-68 wt.-%) compared with the one harboring the wild-type gene (49 wt.-%). Particularly, those evolved PhaC1(Ps) mutants having multiple amino acid substitutions showed higher activities for PHA synthesis. Characterization of the PHA by NMR spectroscopy revealed that they were copolymers consisting of (R)-3-hydroxybutyrate (98-99 mol-%) and medium-chain-length comonomers (1-2 mol-%). This study also confirmed that amino acid substitution at position 481 in PhaC1(Ps) led to an increasing molecular weight of PHA. The number-average molecular weight (Mn) of PHA (Mn = 240,000) synthesized by the evolved PhaC1(Ps) (Q481K) mutant was 4.6-fold greater than that (Mn = 52,000) synthesized by the wild-type enzyme.

Acyltransferases↗

PubMed2005

Total synthesis of the tricyclic marine alkaloids (-)-lepadiformine, (+)-cylindricine c, and (-)-fasicularin via a common intermediate formed by formic acid-induced intramolecular conjugate azaspirocyclization.

A very short and efficient enantioselective total synthesis of the tricyclic marine alkaloids (-)-lepadiformine (3), (+)-cylindricine C (1c), and (-)-fasicularin (4) has been developed utilizing the formyloxy 1-azaspiro[4.5]decane 5 as a common intermediate. The key strategic element for the synthesis was the formic acid-induced intramolecular conjugate azaspirocyclization, which proved to be a highly efficient and stereoselective way to rapid construction of the 1-azaspirocyclic substructure of these natural products in a single operation. Thus, the common intermediate 5, synthesized in two steps with 70% overall yield starting from the known (S)-N-Boc-2-pyrrolidinone 7 via the conjugate spirocyclization using an acyclic ketoamide 6, was utilized for the concise and stereoselective total synthesis of (-)-lepadiformine (3), which was accomplished in seven steps with 45% overall yield from 5 (31% yield from 7). The developed strategy based on the conjugate spirocyclization was also applied to the stereoselective total synthesis of (+)-cylindricine C (1c), which was achieved in 10 steps from 5 in 18% overall yield (12% yield from 7). Further application of this approach using 5 led to the synthesis of (-)-fasicularin (4), wherein an extremely efficient method for the introduction of the thiocyanato group via an aziridinium intermediate at the last step was developed. Thus, the highly efficient first enantioselective total synthesis of (-)-fasicularin was accomplished in nine steps with an overall yield of 41% from 5 (28% yield from 7).

Alkaloids↗

PubMed2005

The selection of pancreatic reconstruction techniques gives rise to higher incidences of morbidity: results of the 30th Japan Pancreatic Surgery Questionnaire Survey on pancreatoduodenectomy in Japan.

BACKGROUND/PURPOSE: We aimed to determine the impact of the surgical strategy used for pancreatic reconstruction on morbidity after pancreatoduodenectomy (PD). METHODS: A questionnaire was sent to all surgeon members of the Japan Pancreatic Surgery Club in December 2002. RESULTS: We received 152 replies, and the data from all of them were used in the analysis. Thirty-six percent of the 152 responders performed PD and selected from among two or more pancreatic reconstruction techniques (PRTs). PRT selection was used no more frequently in the high- and medium-hospital-volume institutions than in low-hospital-volume institutions (25% or 37% vs 35%). The incidence of both "all arterial hemorrhage" and "delayed arterial hemorrhage" after PD in the institutions that used multiple PRTs was significantly higher than that in the institutions where only a single PRT was used (4.2% vs 2.2%, and 3.3% vs 1.5%, respectively; P < 0.05). In the high- and medium-hospital-volume institutions, the incidence of all arterial hemorrhage after PD in the multiple-PRT institutions was significantly higher than that in the single-PRT institutions (4.0% vs 1.9%; P < 0.05). Furthermore, in the low-hospital-volume institutions, the incidence of delayed arterial hemorrhage, 7 or more days after PD, was clearly higher in the multiple-PRT institutions than in the single-PRT institutions (4.1% vs 1.4%; P = 0.056). Therefore, the hospital-case volumes of PD were distributed as practice-case volumes according to the PRT by the selection of PRTs, and PRT selection gave rise to higher incidences of morbidity as a result of pancreatic leakage after PD. CONCLUSIONS: The hospital-case-volume - better outcome relation for PD was attributable to expert pancreatic reconstruction skills that can be mastered only through frequent repetition.

Biliary Tract Surgical Procedures↗

PubMed2005

Effects of hemoglobin vesicles on resting and agonist-stimulated human platelets in vitro.

Hemoglobin vesicles (HbV) are artificial oxygen carriers that encapsulate a concentrated hemoglobin (Hb) solution with a phospholipid bilayer membrane. The oxygen transporting ability of HbV in vivo has been demonstrated by the transfusion of HbV into hemorrhagic shock rodent models. However, the compatibility of HbV with human blood cells must be evaluated. Preincubation of platelets with concentrations of 20% or 40% HbV had no effect on the binding of PAC-1, a monoclonal antibody that detects activation-dependent conformational changes in alphaIIbbeta3 on platelets, or the surface expression of CD62P in whole blood. ADP-induced increases in PAC-1 binding were significantly enhanced by exposing the platelets to concentrations of either 20% or 40% HbV, whereas the ADP-induced increases in CD62P expression were not affected by HbV treatment at either concentration. Preincubation of platelet-rich plasma (PRP) with HbV minimally reduced the spontaneous release of TXB2 and RANTES, but did not significantly affect the formation of TXB2 or the release of RANTES and beta-TG in platelets stimulated with ADP. Similarly, preincubation of PRP with HbV minimally reduced the spontaneous release of RANTES but did not significantly affect the formation of TXB2 or the release of RANTES and beta-TG in platelets stimulated with collagen, although collagen-induced serotonin release tended to decrease with HbV pretreatment. These data suggest that the exposure of human platelets to high concentrations of HbV (up to 40%) in vitro did not cause platelet activation and did not adversely affect the formation and secretion of prothrombotic substances or proinflammatory substances triggered by platelet agonists, although one of the earliest events in ADP-induced platelet activation was slightly potentiated by HbV pretreatment at the doses tested. Taken together, these results imply that HbV, at concentrations of up to 40%, do not have any aberrant interactions with either unstimulated or agonist-induced platelets.

Biomarkers↗

PubMed2005

Mixed serous cystadenoma with mucinous cystadenoma of the pancreas.

We report a case of serous cystadenoma of the pancreas mixed with mucinous cystadenoma. A 65-year-old woman was admitted to our hospital for evaluation of a palpable, elastic, hard mass measuring 6 cm in diameter in the right upper quadrant of the abdomen. A diagnosis of mucinous cystadenocarcinoma of the pancreas was made, and pancreatoduodenectomy was performed. The tumor was composed of a dominant compartment of macroscopic cyst, and its thick wall was filled with numerous microscopic cysts. The light microscopy findings with hematoxylin and eosin staining, and by the periodic acid-Schiff reaction, were almost perfectly consistent with the characteristics of microcystic or glycogen-rich cystadenoma, but the apical portion of the cytoplasm of the neoplastic cells was stained with Alcian blue at pH 2.4 and by the mucicarmine method. Neoplastic cells containing epithelial acidic mucin are usually found in mucinous cystadenomas. No K-ras point mutations were detected at the sites where neoplastic cells were present, whether or not they contained epithelial acidic mucin. Pancreatic serous cystadenomas that include a mucinous-cystadenoma component are extremely rare, and the difference between serous and mucinous cystadenomas is not always distinct.

Aged↗

PubMed2005

Leakage of potassium from red blood cells following gamma ray irradiation in the presence of dipyridamole, trolox, human plasma or mannitol.

Transfusion-associated graft-versus-host disease (TA-GVHD) is a fatal complication of blood transfusion resulting from the contamination of blood products by leukocytes. In order to prevent this disease, gamma or X-ray irradiation of blood components,which can inactivate leukocytes, is currently used. However, the minimal doses needed to destroy lymphocytes promote the leakage of potassium from red blood cells (RBCs), which can induce other side effects, such as hyperpotassemia and cardiac arrest. The reactive oxygen species (ROS) generated by the irradiation of aqueous solutions may accelerate the leakage through oxidation of the RBC membrane. Here we studied the effect of dipyridamole, Trolox, human plasma or mannitol on the leakage of potassium from RBCs following irradiation. RBC preparations (hematocrit; 30%) containing antioxidants were irradiated at 30 Gy and stored at 4 degrees C for 7 d. The leakage of potassium from the RBCs caused by the irradiation was significantly suppressed by dipyridamole (more than 50 microM), Trolox (more than 5 mM) or human plasma (50%). Mannitol (80 mM) is used to inhibit hemolysis as a constituent of MAP solution, which is a solution used for the storage of RBC products in Japan. Here it was clarified that the leakage of potassium from not only irradiated but also non-irradiated RBCs was unexpectedly promoted by mannitol. The amount of mannitol in MAP solution may have to be reconsidered. The osmotic pressure of the RBC preparation increased in a manner dependent on the concentration of mannitol. The elevated osmotic pressure may promote the leakage. In conclusion, although antioxidants have the potential to suppress the leakage of potassium ascribed to the irradiation, the extent of the suppression (10-20%) by dipyridamole (DPM), Trolox or human plasma seems insufficient for the clinical use of these agents as an additive for MAP solution.

Blood↗

PubMed2004

Electrical properties of single-crystalline CaAl2Si2.

Electrical resistivity and Hall coefficient measurements of single-crystalline CaAl(2)Si(2) revealed that CaAl(2)Si(2) is a metal in which both electrons and holes contribute to the transport properties; its dominant carriers are holes at temperature below 150 K but electrons above that temperature.

Journal Article↗