Biomedical subjects

Atsushi Ohashi

Publications and source records attributed to Atsushi Ohashi.

13 recordsLinked to original sources

PubMed2006

A novel apoptosis cascade mediated by lysosomal lactoferrin and its participation in hepatocyte apoptosis induced by D-galactosamine.

A new apoptosis cascade mediated by lysosomal lactoferrin was found in apoptotic liver induced by d-galactosamine. Caspase-3 and lactoferrin were increased in the apoptotic liver cytoplasm and serum transaminases were elevated. Recombinant lactoferrin stimulated procaspase-3 processing at 10(-6)-10(-7)M to an extent similar to that by granzyme B in vitro. Lactoferrin changed procaspase-3 structure susceptible to the processing. Synthetic peptide Y(679)-K(695) in lactoferrin molecule inhibited the processing of procaspase-3 by lactoferrin. Lactoferrin in lysosomes was decreased and lactoferrin released into cytoplasm was increased quantitatively in d-galactosamine induced apoptotic liver, and procaspase-3 in cytoplasm was processed to caspase-3.

Animals↗

PubMed2006

Catechin derivatives: specific inhibitor for caspases-3, 7 and 2, and the prevention of apoptosis at the cell and animal levels.

Tea-catechin derivatives are shown to inhibit activities of caspases-3, 2 and 7 in vitro, and prevented experimental apoptosis at the cell and animal levels. Epigallo-catechin-gallate showed the strongest inhibition at 1 x 10(-7)M to these caspases, but cysteine cathepsins and caspase-8 were not inhibited. Caspase-3 inhibition showed a 2nd-order allosteric-type, but the inhibition of caspases-2 and 7 showed a non-competitive-type. The apoptosis-test using cultured HeLa cells was inhibited by these catechins. In rat hepatocytes, apoptosis was induced by d-galactosamine in vivo. In this case, caspase-3 activity in the cytoplasm, the serum aminotransferases and dUTP nick formation detected by TUNNEL-staining were effects, and these elevations were suppressed by administration of catechin.

Animals↗

PubMed2006

Cytapheresis for the treatment of myeloperoxidase antineutrophil cytoplasmic autoantibody-associated vasculitis: a pilot study of 21 patients.

Twenty-one patients with myeloperoxidase-antineutrophil cytoplasmic autoantibody (MPO-ANCA)-associated vasculitis were treated using cytapheresis. Of these, 17 were treated for glomerulonephritis and four were treated for pulmonary hemorrhage. The overall survival rate was 85.7% with a follow-up duration of 24.0 +/- 13.8 months. In the 17 patients with MPO-ANCA-associated glomerulonephritis, pretreatment creatinine was 3.2 +/- 1.6 mg/dL, and renal function recovered in 76.5%. Pulmonary hemorrhage was ameliorated in all four patients. Abdominal pain occurred in three of the 21 patients but symptoms resolved soon after the cytapheresis procedure was completed. No other adverse effects occurred during cytapheresis. From these results, cytapheresis can be considered a safe and effective treatment for MPO-ANCA-associated vasculitis. As for the mechanism of its action, soluble tumor necrosis factor receptor 1 (sTNFR), sTNFR2 and interleukin 1 receptor antagonist were elevated soon after cytapheresis and those levels 2 h after the cytapheresis procedure were higher than before the procedure in some cases. These elevations might be related to the efficacy of cytapheresis.

Aged↗

PubMed2006

[Bronchial blocking with a balloon wedge pressure Catheter in a small infant].

The need for one-lung ventilation has been increasing even in pediatric patients. However, the trachea is so narrow in pediatric patients that ordinary double-lumen tubes can not be used and there have been many reports on devices or measures to block one lung. We report our experience with a female infant weighing 2 kg who had severe chronic lung disease under mechanical ventilation, and underwent left lung lower lobectomy with one-lung ventilation technique. We chose a balloon wedge pressure catheter to block the left main bronchus, because it has a central lumen through which a guide wire can be passed and sucking is available. The infant was in need of continuous ventilation and the catheter was too soft to be inserted directly. We first inserted an 18G catheter of a needle-catheter assemble outside the tracheal tube through which a guide wire was inserted into the left main bronchus with the aid of direct vision of a 2-mm fiberoptic bronchoscope through the tracheal tube, and then inserted the balloon wedge pressure catheter placing it in an appropriate position. One-lung ventilation was successfully achieved and the operative and postoperative course was uneventful.

Catheterization↗

PubMed2005

Two-photon absorption properties of self-assemblies of butadiyne-linked bis(imidazolylporphyrin).

Supramolecular porphyrin self-assemblies have been prepared from butadiyne-linked bis(imidazolylporphyrin) by complementary coordination of imidazole to zinc, and their two-photon absorption (2PA) and higher-order nonlinear absorption properties were investigated over femtosecond time scales using an open-aperture Z-scan method. The self-assembled porphyrin dimer of the conjugated monozinc bisporphyrin 7D was shown to have a large 2PA cross section (7.6 x 10(3) GM, where 1 GM = 10(-50) cm(4) s molecule(-1) photon(-1)) at 887 nm. By comparison of this result with that for a meso-meso-linked porphyrin array without the butadiyne connection (3.7 x 10(2) GM at 964 nm), it was demonstrated that the predominant factor in this significant enhancement of the cross section was the expansion of porphyrin-porphyrin pi-conjugation. Self-coordination and monozinc metalation were also found to be contributing factors. Furthermore, a novel self-assembled porphyrin polymer 8P consisting of a biszinc complex with a mean molecular weight of M(n) = 1.5 x 10(5) Da was shown to exhibit an extraordinarily large two-photon absorption cross section (4.4 x 10(5) GM at 873 nm). Nanosecond Z-scan experiments for 7D and 8P were also undertaken and resulted in the measurement of large effective 2PA cross sections, including the excited-state absorption (2.1 x 10(5) GM for 7D and 2.2 x 10(7) GM for 8P, respectively). Finally, three-photon absorption was observed by femtosecond Z-scan experiments at 1188 nm (7.1 x 10(-89) m(6) s(2)) and 1282 nm (1.8 x 10(-89) m(6) s(2)), an observation which is the first of its kind in porphyrin chemistry.

Alkynes↗

PubMed2005

Reverse zymography using fluorogenic substrates for protease inhibitor detection.

A novel, sensitive method for detecting protease inhibitors by using fluorescent protease substrates in gels is described. The protease inhibitors were separated on sodium dodecyl sulfate (SDS)-polyacrylamide gels containing a copolymerized peptide substrate, namely 4-methyl-coumaryl-7-amide (MCA). As the incorporated substrates in the gel, Boc-Phe Ser-Arg-MCA was used for trypsin, Suc-Ala-Ala-Pro-Phe-MCA for alpha-chymotrypsin, and Z-Phe-Arg-MCA for papain. After electrophoresis, washing and incubating the gel with the target protease solutions allowed the substrate to be cleaved by the protease, and the release of the fluorescent 7 amino-4 methyl-coumarin (AMC), which was detected under a UV transilluminator. The uncleaved peptide-MCA substrate remained where the inhibitors were present, and was visualized as dark blue bands on the light-green fluorescent background gel. This new method offers several advantages over other previous methods including: (i) greatly increased sensitivity can be achieved in a shorter period of time, which may be useful for discovering new protease inhibitors in small amounts of crude material; (ii) the procedure is quite simple and quick since the incubation period is very short and no time is needed for staining and destaining steps; (iii) since these probes using substrate specificity/target proteases, they are excellent tools for detection and discrimination of unknown protease inhibitors for various target proteases.

Animals↗

PubMed2005

Evaluation of endocrine disrupting activity of plasticizers in polyvinyl chloride tubes by estrogen receptor alpha binding assay.

Polyvinyl chloride (PVC) tubing is an indispensable medical material for extracorporeal circulation therapy. However, di(2-ethylhexyl)phthalate (DEHP), a suspected endocrine disruptor, can be eluted from PVC, suggesting that an alternative material that does not contain DEHP is needed for clinical applications. First, we evaluated the endocrine disrupting risks of the plasticizers contained in PVC tubes by investigating their binding affinities for the human estrogen receptor alpha (ERalpha). Our results revealed that, while DEHP has some binding affinity for ERalpha, neither epoxidized soybean oil nor tris(2-ethylhexyl)trimellitate (an alternative to DEHP) has any affinity for ERalpha. Second, we evaluated the endocrine disrupting risks of a tube made of newly developed plasticizer-free (PF) materials. We confirmed the presence of DEHP and detected several unidentified substances in plasma stored within the PVC tube. This plasma's competitive binding affinity for ERalpha was significantly higher than that of control plasma (P < 0.01). In contrast, the profile of plasma stored in the PF tube was similar to that of the control, both in terms of high-performance liquid chromatography chromatograms and competitive binding capacity for ERalpha, suggesting that the PF tube is biocompatible and is useful for reducing the elution of substances capable of binding to ERalpha.

Chromatography, High Pressure Liquid↗

PubMed2005

Variant clinical courses of 2 patients with neonatal intrahepatic cholestasis who have a novel mutation of SLC25A13.

Deficiency of citrin due to mutations of the SLC25A13 gene causes not only adult-onset type II citrullinemia, but also neonatal intrahepatic cholestasis. Neonatal intrahepatic cholestasis is a self-limiting condition and spontaneously disappears by 12 months of age without special treatment. The natural history of patients with SLC25A13 mutations is not clear. Two patients with infantile hepatic dysfunction were found to have a novel mutation of the SLC25A13 gene. DNA analyses of SLC25A13 disclosed that the first patient was a compound heterozygote for the Ex16+74_IVS17-32del516 (del516-Ex16/IVS17) and IVS11+1G-->A mutations and the second one a homozygote for the del516-Ex16/IVS17 mutation. It is predicted that the 516-base pair deletion mutation leads to a frameshift from codons 556 to 564, a premature termination at codon 565, and a truncated form of the citrin protein (normal, 675 amino acids). The first patient had disseminated intravascular coagulation associated with hepatic dysfunction in the neonatal period. The other patient had persistent cholestatic jaundice and underwent an operation to rule out bile duct atresia. Without specific treatment, both patients had a favorable clinical course. In conclusion, citrin deficiency resulting from the mutation of SLC25A13 presented variant clinical courses, followed by hypercitrullinemia and intrahepatic cholestasis in infancy. The conditions in the patients were self-limiting and spontaneously disappeared.

Cholestasis, Intrahepatic↗

PubMed2005

[Anesthetic management of an 18-trisomy neonate with high frequency ventilation].

Neonates with 18-trisomy syndrome have various anomalies including cardiac and facial anomalies. Active treatments for them have not been recommended due to a low survival over one year which is less than 10%. However, the survival over one year in our institute between 1985 and 2003 is higher at 22%, and we had a patient with survival of over 5 years. We report a case of anesthetic management in a male 18-trisomy neonate who received a radical repair of umbilical hernia immediately after his birth. Tracheal intubation was difficult due to small airway and facial anomalies; cleft clip, cleft palate, and macrognathia. Conventional ventilation was ineffective for elimination of carbon dioxide and oxygenation due to pulmonary hypoplasia and intra- and extra-cardiac shunts. A high frequency ventilation improved elimination of carbon dioxide and oxygenation.

Abnormalities, Multiple↗

PubMed2004

New apoptosis cascade mediated by lysosomal enzyme and its protection by epigallo-catechin gallate.

We found a novel procaspase-3 activating cascade mediated by lysosomal enzyme. The activating enzyme of procaspase-3, named lysoapoptase having the molecular weight of 78kDa was determined to be a lactoferrin located in the lysosome. Recombinant lactoferrin accelerated the processing of procaspase-3 to form active caspase-3 in vitro. D-Galactosamine is a well-known inducer of hepatocyte apoptosis. The caspase-3 which plays a common central role in the final step of various apoptosis cascades, was dramatically increased in the cytoplasm by the d-galactosamine administration in vivo. When D-galactosamine was administrated as a death signal in vivo, the lysosomal lactoferrin was released into the cytoplasm and procaspase-3 located in the cytoplasm was processed to form active caspase-3. The cotreatment of epigallo-catechin gallate resulted in the complete protection of the hepatocyte apoptosis suppressing the increases of caspase-3 in the cytoplasm. The caspase-3 activity was also inhibited directly by the epigallo-catechin gallate. Therefore, all apoptosis cascades mediated by caspase-3 should be suppressed by epigallo-catechin gallate. The caspase-3 activity was not only directly inhibited by epigallo-catechin gallate in vitro, but the release of lactoferrin from the lysosomes into the cytoplasm was also suppressed by epigallo-catechin gallate treatment in vivo. Therefore, the apoptosis induction was suppressed at the two successive steps by cotreatment of epigallo-catechin gallate in vivo.

Amino Acid Substitution↗

PubMed2004

[Propofol anesthesia for fetal sedation].

We were requested to reduce neonatal respiratory effort at delivery in anesthetic management for Cesarean section. A 26-year-old pregnant woman was suspected through abdominal ultrasound examination and amniotic fluid test, of her baby having immature lungs associated with remarkable pleural effusion. Lungs could be damaged by respiratory effort after delivery, and respiratory management immediately after delivery was planned. Anesthesia was induced with propofol and fentanyl 300 micrograms. Propofol was administered with a target controlled infusion setting with the target blood concentration of 10 micrograms.ml-1. Fetal electrocardiogram was monitored for detecting fetal sedation. The concentrations of propofol at delivery were 10.7 and 4.1 micrograms.ml-1 in maternal arterial and umbilical venous blood, respectively, and the baby was apneic. Respiration of the baby was managed with a high frequency jet ventilation mode, and 160 ml of pleural effusion was aspirated immediately after the delivery. The baby was discharged from the hospital 5 weeks afterward.

Adult↗

PubMed2003

Strong two-photon absorption of self-assembled butadiyne-linked bisporphyrin.

Two-photon absorption (2PA) properties of self-assembled porphyrins were investigated. The butadiyne-linked porphyrin array exhibited a 20 times larger 2PA cross section than the meso-meso-linked self-assembled array due to the expansion of pi-conjugation. Higher-order nonlinear absorption was also observed in the former porphyrin.

Journal Article↗

PubMed2002

Mechanism of asymmetric hydrogenation by rhodium complexes with unsymmetrical P-chirogenic bisphosphine ligands.

Using a series of the rhodium complexes with (1S,2S)-1-(R(1))methylphosphino-2-(R(2))(R(3))phosphinoethane (R(1), R(2) and R(3) = 1-adamantyl, t-butyl, cyclohexyl, cyclopentyl, methyl; abbreviated as unsymmetrical BisP*), very high enantioselectivities were observed when the di- or tri- substituted and tetra-substituted dehydro-alpha-amino acid derivatives were used as the substrates. The main factor to give high enantioselectivity is the repulsive interaction between the functional groups of the substrate and the bulky substituents of the unsymmetrical BisP*. Since the unsymmetrical BisP* has two independent chiral phosphorous atoms in the vicinity of the active site, the higher enantioselectivity than those by the C2 symmetric BisP* complexes can be obtained. Moreover, the fine-tuning to obtain extremely high enantioselectivity may be possible by changing the combination of the substituents on the two phosphorous atoms of the unsymmetrical BisP*.

Amino Acids↗