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Biomedical subjects

K Kusumoto

Publications and source records attributed to K Kusumoto.

At least 55 records · Page 3Linked to original sources
PubMed1997

Electrolyzed-reduced water scavenges active oxygen species and protects DNA from oxidative damage.

Active oxygen species or free radicals are considered to cause extensive oxidative damage to biological macromolecules, which brings about a variety of diseases as well as aging. The ideal scavenger for active oxygen should be 'active hydrogen'. 'Active hydrogen' can be produced in reduced water near the cathode during electrolysis of water. Reduced water exhibits high pH, low dissolved oxygen (DO), extremely high dissolved molecular hydrogen (DH), and extremely negative redox potential (RP) values. Strongly electrolyzed-reduced water, as well as ascorbic acid, (+)-catechin and tannic acid, completely scavenged O.-2 produced by the hypoxanthine-xanthine oxidase (HX-XOD) system in sodium phosphate buffer (pH 7.0). The superoxide dismutase (SOD)-like activity of reduced water is stable at 4 degrees C for over a month and was not lost even after neutralization, repeated freezing and melting, deflation with sonication, vigorous mixing, boiling, repeated filtration, or closed autoclaving, but was lost by opened autoclaving or by closed autoclaving in the presence of tungsten trioxide which efficiently adsorbs active atomic hydrogen. Water bubbled with hydrogen gas exhibited low DO, extremely high DH and extremely low RP values, as does reduced water, but it has no SOD-like activity. These results suggest that the SOD-like activity of reduced water is not due to the dissolved molecular hydrogen but due to the dissolved atomic hydrogen (active hydrogen). Although SOD accumulated H2O2 when added to the HX-XOD system, reduced water decreased the amount of H2O2 produced by XOD. Reduced water, as well as catalase and ascorbic acid, could directly scavenge H2O2. Reduce water suppresses single-strand breakage of DNA b active oxygen species produced by the Cu(II)-catalyzed oxidation of ascorbic acid in a dose-dependent manner, suggesting that reduced water can scavenge not only O2.- and H2O2, but also 1O2 and .OH.

Ascorbic Acid↗
PubMed1997

Intramuscular osteoinduction and bone marrow formation by the implantation of rhBMP-2 with atelopeptide type I collagen.

The study examines the osteoinductive potential of recombinant human morphogenetic protein 2 (rhBMP-2) radiologically and histologically in rat calf muscle. Ten male Wistar rats were used. rhBMP-2 50 microg was implanted with atelopeptide type I collagen as carrier in a pouch in rat calf muscle (n = 5), and atelopeptide type I collagen alone was implanted in a further five as control. Induction of osteogenesis at 4 weeks was investigated. In all rats in which rhBMP-2 had been implanted there was a radio-opaque shadow in the muscle in the soft tissue radiograph. No such shadows were noted in the control group. Histological examination showed bony trabeculum, osteoblasts, and vigorous bone marrow including fatty marrow and angioid tissue both at the margins and in the center of the excised lumps in the rhBMP-2 group. There were no such signs in the control group. rhBMP-2 may be capable not only of inducing the formation of bone, but also of inducing a 'self-supporting bone organ' in the muscle.

Animals↗
PubMed1996

Pharmacological characterization of cardiovascular responses induced by endothelin-1 in the perfused rat heart.

The effects of the endothelin receptor antagonist TAK-044 (cyclo[D-alpha-aspartyl-3-[(4-phenylpiperazin-1-yl)carbonyl]-L-ala nyl-L-alpha-aspartyl-D-2-(2-thienyl)glycyl-L-leucyl-D-tryptophyl]+ ++disodiu m salt) and BQ-123 (cyclo[D-Asp-Pro-D-Val-Leu-D-Trp]) were studied in the rat heart to characterize the receptor subtypes responsible for the cardiovascular actions of endothelin-1. Endothelin-1 induced a transient decrease and subsequent increase in perfusion pressure in perfused rat hearts, and increased left ventricular developed pressure. TAK-044 diminished these endothelin-1-induced responses (100 pmol/heart) with IC50 values of 140, 57 and 1.3 nM, respectively. BQ-123 (1-30 mu M) partially inhibited the endothelin-1-induced hypertension (30-40%) in the rat heart, and failed to inhibit the hypotension. The positive inotropic effect of endothelin-1 was abolished by BQ-123. Neither indomethacin (10 mu M) nor Nomega-nitro-L-arginine methyl ester (100 mu M) attenuated the endothelin-1-induced hypotension. TAK-044 and BQ-123 attenuated the positive inotropic effect of endothelin-1 in rat papillary muscles. In rat cardiac membrane fractions, TAK-044 and BQ-123 inhibited [125I]endothelin-1 binding to endothelin ET(A) receptors with IC50 values of 0.39 +/- 0.6 and 36 +/- 9 nM, respectively, whereas only TAK-044 potently blocked the endothelin ET(B) receptor subtype (IC50 value: 370 +/- 180 nM). These results suggest that endothelin-1 modulates cardiovascular functions in the rat heart by activating both endothelin ET(A) and endothelin ET(B) receptors, all of which are sensitive to TAK-044.

Analysis of Variance↗
PubMed1996

Self-regenerating bone implant: ectopic osteoinduction following intramuscular implantation of a combination of rhBMP-2, atelopeptide type I collagen and porous hydroxyapatite.

A combination of recombinant human bone morphogenetic protein-2 (rhBMP-2), atelopeptide Type I collagen (CL) as a carrier and porous hydroxyapatite (pHAP) was implanted in a calf muscle pouch of the rat. Three rhBMP-2-implanted groups (2, 10 and 50 micrograms; each n = 5) and the control group (n = 5), in which only CL and pHAP were implanted, were established. Three weeks later, the implants were examined.

Animals↗
PubMed1996

Study of the changes of serum hyaluronic acid during porcine liver transplantation: influence of warm ischemia.

Twelve porcine liver transplantations were performed to investigate whether serum hyaluronic acid (HA) serves as a marker of warm ischemic injury. Group 1 was a control without warm ischemia (n = 7), and pigs in Group 2 were sacrificed by intracardiac KCl injection 60 min before harvesting (n = 5). All pigs survived more than 4 days in Group 1. In Group 2, all died within 2 days due to graft failure. Arterial and hepatic venous glutamic-oxaloacetic transaminase (GOT) in Group 2 were higher after revascularization. However, there were no differences between the 2 groups in arterial and hepatic venous HA levels. HA clearance by the graft also showed no differences between the groups. Although GOT reflected the degree of warm ischemia, HA and its hepatic clearance were not influenced by warm ischemic damage. In conclusion, HA was not thought to serve as a marker of liver injury when the graft suffered from warm ischemia.

Animals↗
PubMed1996

Purification and characterization of the esterases involved in aflatoxin biosynthesis in Aspergillus parasiticus.

The esterases from the cell-free extracts (CFEs) of Aspergillus parasiticus ATCC15517, an aflatoxin-producing strain, catalyzing the hydrolytic conversion of versiconal hemiacetal acetate (VHA) to versiconal was biochemically studied. The specific activity of the enzymes increased 2.5-fold during incubation of mycelia through 40-55 h. No metal ions were required for enzyme stability, but EDTA at 1 mM and dithiothreitol at 0.5-5 mM increased its stability. Three peaks of VHA esterase activity were resolved when the proteins in the CFEs prepared from the mycelia of different ages were separated by anion-exchange column chromatography, suggesting that at least three VHA esterases were present in the eluate of this purification step. One of these esterases extracted from the mycelia of a 55-h culture was partially purified in five steps by means of preparative chromatography and fast protein liquid chromatography. The partially purified enzyme when reacted with [14C]diisopropylfluorophosphate followed by sodium dodecyl sulfate - polyacrylamide gel electrophoresis gave a single radiolabelled band, which corresponded to a protein of 32 kDa. The molecular mass of the partially purified VHA esterase determined with gel filtration was around 60 kDa. The results suggested that the enzyme consists of two isomeric subunits.

Aflatoxins↗
PubMed1996

[A case of right postpneumonectomy empyema treated by open window thoracostomy, thoracoplasty, pedicled omental flap and musculocutaneous flaps].

A case of right postpneumonectomy empyema treated by open window thoracostomy, thoracoplasty, pedicled omental flap and musculocutaneous flaps is reported. After open window thoracostomy, pedicled omental flap and musculocutaneous flaps transplantation utilizing techniques used in plastic surgery were performed, and right postneumonctomy empyema was successfully treated. In this study, open window thoracostomy was effective against depuration of the empyema cavity and omental and musculocutaneous flaps against the infection control and plombage of the cavity. Furthermore, to maximize the effect of musculocutaneous flaps and to use them effectively, it is thought that techniques utilized in plastic surgery are effective and necessary.

Adenocarcinoma↗
PubMed1995

Comparative study of bone marrow induced by purified BMP and recombinant human BMP-2.

Into a calf muscle pouch in Wistar rats, 50 micrograms purified bone morphogenetic protein (pBMP) or 50 micrograms recombinant human bone morphogenetic protein-2 (rhBMP-2) was implanted using atelopeptide type I collagen solution (CL) as a carrier. Three weeks later bone and bone marrow were induced in both groups. These induced bone and bone marrow were studied histologically. In the pBMP+CL group (n = 5), rich bone matrix and little bone marrow were observed. There was no fatty marrow or angioid tissue observed. In the rhBMP-2+CL group (n = 5), bone matrix and rich marrow including fatty marrow and angioid tissue were observed around and among the bony trabeculae. It was suggested that a "self-supporting bone organ" was induced.

Animals↗
PubMed1995

Experimental studies on bone inducing activity of composites of atelopeptide type I collagen as a carrier for ectopic osteoinduction by rhBMP-2.

Atelopeptide type I collagen derived from fresh porcine skin was evaluated as a carrier for ectopic osteoinduction by recombinant human bone morphogenetic protein-2 (rhBMP-2) in rats. Four treatment groups (N = 5) were examined: a control group in which only atelopeptide type I collagen was implanted, and groups II, III and IV in which atelopeptide type I collagen with 2, 10, 50 micrograms of rhBMP-2 was implanted in to the calf muscles of 10-week-old Wistar rats, respectively. Four weeks after the implantation, soft X-ray and light microscopic examinations were performed. In addition, calcium (Ca) content and alkaline phosphatase (ALP) activity were evaluated. New bone formation in the implanted regions (groups II, III and IV) were revealed. Bone formation was induced in the implanted region of even 2 micrograms of rhBMP-2 (group II), and its degree was dependent on the dose of rhBMP 2. These results indicate that atelopeptide type I collagen is an effective carrier for ectopic osteo-induction by rhBMP-2 and may act as a carrier for rhBMP in reconstructive surgery for bony defect and augmentation.

Alkaline Phosphatase↗
PubMed1995

An analogue of lipid A and LPS from Rhodobacter sphaeroides inhibits neutrophil responses to LPS by blocking receptor recognition of LPS and by depleting LPS-binding protein in plasma.

When incubated with lipopolysaccharide (LPS) in the presence of plasma, neutrophils become primed for enhanced release of superoxide in response to triggering by formyl-Met-Leu-Phe (fMLP). The effect of LPS on phagocytes is inhibited by a synthetic lipid A precursor, LA-14-PP (lipid IVa) or by LPS from Rhodobacter sphaeroides (Rs). We studied the mechanisms by which LA-14-PP or Rs-LPS inhibited LPS-induced responses. When neutrophils were exposed to LA-14-PP or Rs-LPS for 3 min and then to Escherichia coli-LPS, the antagonists inhibited priming for superoxide release, and also blocked up-regulation of CD11b and adherence. This inhibition was dependent on plasma, was not overcome by higher amounts of E. coli-LPS or plasma, and was not observed at 0 degrees C, suggesting that E. coli-LPS was not able to interact with its receptor or other cellular recognition molecule in neutrophils that had been exposed to the antagonists. The alternative possibility that LA-14-PP or Rs-LPS depleted a plasma cofactor, resulting in inhibition of priming, was investigated by using LPS from Porphyromonas gingivalis (Pg) and Bordetella pertussis (Bp). These LPS primed neutrophils in a plasma-dependent and CD14-dependent manner, but were not blocked by LA-14-PP or Rs-LPS. When sub-optimal concentrations of plasma were exposed to LA-14-PP or Rs-LPS, and then mixed with Pg-LPS or Bp-LPS, followed by incubation with neutrophils, priming and up-regulation of CD11b were inhibited, and this inhibition was overcome by increasing the concentration of plasma. Binding of LPS-binding protein (LBP) in plasma to immobilized E. coli-LPS was inhibited by pre-incubation of plasma with LA-14-PP or Rs-LPS. Together with the result that treatment of plasma with anti-LBP antibody abolished the cofactor activity of plasma, these results indicated that LA-14-PP and Rs-LPS depleted LBP from plasma, resulting in inability of LPS to act on neutrophils. Thus LA-14-PP and Rs-LPS inhibited the action of LPS on neutrophils by at least two mechanisms, blocking of LPS receptor recognition and depletion of the cofactor LBP.

Acute-Phase Proteins↗
PubMed1995

Pharmacology of a non-selective ETA and ETB receptor antagonist, TAK-044 and the inhibition of myocardial infarct size in rats.

1. The aims of the present study were to characterize the pharmacological profile of a new endothelin (ET) receptor antagonist, TAK-044 and to consider whether it limits the extension of myocardial infarct size in rats. 2. Binding of [125I]-ET-1 to ET receptors on rabbit ventricular and cerebellar membrane fractions was inhibited by TAK-044 with IC50 values of 3.8 nM and 130 nM, respectively. 3. It inhibited ET-1, ET-2 and ET-3-induced vasoconstriction of porcine isolated coronary arteries in a competitive (ET-1, ET-2) and a non-competitive (ET-3) manner. 4. In the rat in vivo, the ET-1-induced blood pressure changes including transient hypotension followed by sustained hypertension, were inhibited by TAK-044 (0.1-10 mg kg-1, i.v.) in a dose-dependent manner. 5. Acute myocardial infarction induced by 1 h coronary occlusion followed by 24 h reperfusion in rats caused an infarct size of 60 +/- 2% (n = 12) of the area-at-risk by weight. 6. Intravenous injection of TAK-044 10 min before coronary occlusion reduced the infarct size in a dose-dependent manner: 32% and 54% reductions at 1 and 3 mg kg-1, respectively. 7. TAK-044 administered 10 min before or 1 h after reperfusion (1 mg kg-1, i.v.) showed similar inhibitory effects: 34% and 23% reductions, respectively. 8. We conclude that TAK-044 is an ETA/ETB receptor antagonist which shows strong inhibitory effects on the extension of myocardial infarct size after coronary artery occlusion-reperfusion in rats.

Animals↗
PubMed1995

Allopurinol effects in rat liver transplantation on recovery of energy metabolism and free radical-induced damage.

Rat livers were orthotopically transplanted after 90-min cold ischemia (group 1) or after 20-min warm and 70-min cold ischemia without (group 2) or with (group 3) allopurinol treatment (AT) (50 mg/kg i.v. 10 min prior to warm ischemia into the donor, flush perfusates with 1 mmol/l). Recovery processes were followed up for 60 min of reperfusion. Liver tissue levels of ATP and total adenine nucleotides were restored in group 1 to almost preischemic ranges within 15-30 min, remained significantly reduced by 30 and 20%, respectively, in group 2, and recovered with AT within 60 min in group 3 to almost the same extent as in group 1. A massive increase in the tissue malondialdehyde concentration, indicative of lipid peroxidation, occurred in the beginning of reperfusion of warm-ischemically damaged donor livers, which in group 3 with AT tended to be less pronounced than in group 2 without AT. The GSSG/GSH ratio reflecting intracellular oxidant stress averaged 3.3 x 10(-3) in group 1 between 15 and 60 min reperfusion. In group 3 AT resulted in comparably low values averaging 3.8 x 10(-3), while in warm-ischemically damaged livers without AT of group 2 this ratio was significantly and continuously elevated averaging 5.8 x 10(-3).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗
PubMed1995

[A case of ANCA negative Wegener's granulomatosis with pulmonary giant bulla showing high level of soluble ICAM-1].

This paper reports a rare case of the limited form of Wegener's granulomatosis (WG) with pulmonary giant bulla, which was pathologically identified only in the lung and showed a high level of soluble intercellular adhesion molecule-1 (ICAM-1) but not anti-neutrophil cytoplasmic antibody (ANCA). A 46 year-old male was admitted for the further examination of right anterior chest pain and dyspnea. Chest X-ray and CT examination showed giant bulla accompanied with the invasive lesions in upper lobe of right lung. Partial lobectomy was done. Granulomatous and necrotizing vasculitis characteristics of WG were confirmed by the histopathology of resected tissues. Immunological analysis on admission showed a high level of soluble ICAM-1 and ANCA negative, but that of soluble ICAM-1 was reduced after surgical operation and remained within normal range during an administration of prednisolone and cyclophosphamide. These results suggest that soluble ICAM-1 may be one of the useful parameters for a diagnosis of WG and for an estimation of its treatments, especially in the cases of ANCA negative WG.

Antibodies, Antineutrophil Cytoplasmic↗