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Biomedical subjects

K Kusumoto

Publications and source records attributed to K Kusumoto.

At least 19 recordsLinked to original sources
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↗
PubMed1995

Increase in length of experimental skin flaps that survive with dibutyryl cyclic AMP.

One of the most important research topics in plastic surgery is the extension of the length of skin flaps that survive. We have investigated the increase in the length of skin flaps that can be achieved by giving dibutyryl cyclic AMP (DB-cAMP) to rabbits with experimental skin flaps and compared the results with those in animals not given DB-cAMP. Three variables, the arrival of DB-cAMP in the critical area of circulation of the flap (n = 6), changes in the blood flow in the flap (n = 10), and increase in the length of skin flap that survived (n = 30) were investigated by high performance liquid chromatography and laser Doppler flowmetry. DB-cAMP reached the critical area of circulation in the skin flap (dye distance), increased the blood flow within this area (mean (SEM) peak value 30 minutes after operation 1.24 (0.06) ml/min/kg compared with 1.06 (0.02) in control flaps), and extended the length of the flap that survived (mean (SEM) length seven days after operation 66.1 (3.0) mm compared with 60.8 (1.8) mm in the control group). We conclude that DB-cAMP improved the blood flow in skin flaps in rabbits with a consequent increase in the length of skin flap that survived.

Animals↗
PubMed1995

Eradication of poliomyelitis: progress in the People's Republic of China.

China and the other countries of the Western Pacific Region have a goal of eradication of wild poliovirus by the end of 1995. In this report we examine the progress made toward eradication through the end of 1993. We examined the information about poliomyelitis and wild poliovirus based on the acute flaccid paralysis surveillance system. The number of reported poliomyelitis cases decreased from 4623 cases in 1989 and 5065 cases in 1990, which occurred during a large nationwide poliomyelitis epidemic, to 538 cases in 1993. Mass supplemental immunization sessions were conducted during the 1991 to 1992 and 1992 to 1993 winters. After the two rounds of supplemental immunizations in the 1992 to 1993 winter, wild poliovirus was not detected for the subsequent 21 months in 22 contiguous provinces in central and northern China, in which 980 million persons reside. In 1993 wild poliovirus was detected in only 5 provinces in southern China and in 2 provinces in the remote Western region; these provinces have only 14% of the total population in China. China is close to achieving its 1995 poliomyelitis elimination goal. Mass supplemental immunizations in children 0 to 3 years old can rapidly eliminate wild poliovirus from large, very densely populated areas, low income rural areas and remote mountainous areas. There appears to be no technical obstacle, even in the most difficult areas, to achieving global eradication of wild poliovirus by the year 2000.

Child↗
PubMed1994

Cyclic hexapeptide endothelin receptor antagonists highly potent for both receptor subtypes ETA and ETB.

A cyclic hexapeptide, cyclo(-D-Asp-Trp-Asp-D-Leu-Leu-D-Trp-), designed from cyclo(-D-Glu-Ala-D-alloisoleucyl-Leu-D-Trp-), an ETA receptor-selective antagonist, possessed not only affinity similar to that of BQ-123 for ETA but also higher affinity for ETB than BQ-123. Further modification led to the discovery of cyclo(-D-Asp-Asp(Php)-Asp-D-Thg-Leu-D-Trp-) (Asp(Php): 1-beta-aspartyl-4-phenylpiperazine; Thg: 2-(2-thienyl)glycine) that inhibited [125I]ET-1 binding to the ETA and ETB receptors with IC50 values of 0.082 nM and 120 nM, respectively. Although this compound possesses 1470-fold less affinity for ETB than for ETA, it behaves as a non-selective antagonist that equipotently inhibits vasoconstriction mediated by both receptor subtypes ETA and ETB.

Amino Acid Sequence↗
PubMed1994

Effects of a new endothelin antagonist, TAK-044, on post-ischemic acute renal failure in rats.

Protective effects of a new endothelin (ET) receptor antagonist, TAK-044, were studied in a model of acute renal failure (ARF) in rats. ARF was induced by clamping the left renal pedicle for 45 minutes with contralateral nephrectomy and subsequent reperfusion of the left kidney. Plasma creatinine concentration (Pcr) increased to 2.28 mg/dl 24 hours after reperfusion of the ischemic kidney. Intravenous administration of TAK-044 (1-10mg/kg) prior to renal occlusion dose-dependently but partially attenuated the increase in Pcr and the morphological damages of the kidney. ET-1 and ET-3 increased perfusion pressure in isolated kidney preparations with similar potency, indicating that the renal vasoconstriction evoked by these ET isomers is mainly via ETB receptors, and TAK-044 (10nM) shifted the ET-1 dose-response curve to the right by a factor about 10. In a rat renal membrane fraction, ET-1 showed competitive inhibition of specific [125I]ET-1 binding with an IC50 value of 0.34nM and a Hill slope of 1.10. ET-3 did so with a higher IC50 value (3.3nM) and a lower Hill slope (0.56), suggesting that rat kidney contains both ETA and another receptor subtype, probably ETB. TAK-044 inhibited ET-1 binding with an IC50 value of 6.6nM and a Hill slope of 0.41. Plasma concentrations of immunoreactive TAK-044 were maintained over 7nM for 8 hours following i.v. injection of 10mg/kg TAK-044. These results suggest that endogenous ET is involved in the pathogenesis of post-ischemic ARF, at least, in part and that TAK-044 provided protective effects against ARF by blocking ET receptors, possibly both ETA and ETB receptors in renal vasculature and parenchymal cells.

Acute Kidney Injury↗
PubMed1994

The gonial angle stripper: an instrument for the treatment of prominent gonial angle.

In the Orient, a prominent gonial angle, so-called benign masseteric hypertrophy, is rather common and considered unattractive. Therefore, its surgical correction is one of the most popular forms of facial skeletal contouring. For accurate and safe osteotomy of the mandibular angle region, a gonial angle stripper was specially invented. It has a small projection that will ease identification of the osteotomy line in a narrow operative field. The tool has been clinically used in eight patients to prove its usefulness, especially for a posteriorly developed mandibular angle.

Adolescent↗
PubMed1994

Antihypertensive and cardiovascular effects of a new potassium channel opener, TCV-295, in rats and dogs.

The antihypertensive and cardiovascular properties of a new potassium channel opener, TCV-295, were studied in rats and dogs. In conscious, spontaneously hypertensive rats (SHR), TCV-295 (0.03-1 mg/kg orally, p.o.) reduced blood pressure (BP) dose dependently with slow onset of action. The antihypertensive effects induced by TCV-295 lasted much longer than those of levcromakalim and nisoldipine, and the reflex tachycardia it evoked was less marked than that evoked by these drugs as compared at doses showing similar maximal hypotensive effects. Glibenclamide (30 mg/kg intravenously, i.v.) inhibited the TCV-295-induced BP decrease in anesthetized rats. In a 4-week chronic dosing study in SHR, TCV-295 (0.3 mg/kg/day p.o.) produced neither potentiation nor tolerance to its antihypertensive action and no rebound hypertension occurred when drug treatment was discontinued. In anesthetized normotensive dogs, TCV-295 (4.5 micrograms/kg/min i.v.) induced BP reductions accompanied by reductions in systemic vascular resistance. TCV-295 also reduced resistances of the coronary, vertebral, mesenteric, and renal vascular beds, and the most marked effect was observed in the coronary vasculature. Myocardial O2 consumption was reduced by TCV-295, possibly owing to afterload decrease. These results suggest that TCV-295 has a desirable profile for an antihypertensive agent.

Administration, Oral↗
PubMed1994

A new endothelin receptor antagonist, TAK-044, shows long-lasting inhibition of both ETA- and ETB-mediated blood pressure responses in rats.

The present study describes the pharmacological profile of an endothelin (ET) receptor antagonist, TAK-044, in anesthetized rats. TAK-044 given 10 min before administration of ET-1 (0.3 nmol/kg i.v.) partially inhibited the ET-1-induced pressor response at 0.1 and 1 mg/kg i.v. and almost completely inhibited the response at a dose of 10 mg/kg. The transient depressor response induced by ET-1 was also inhibited by 1 and 10 mg/kg TAK-044. BQ-123 partially inhibited the pressor response at 0.1-10 mg/kg i.v., whereas it did not inhibit the depressor response except at a dose of 10 mg/kg. These inhibitory effects of TAK-044 were longer lasting than those of BQ-123: 3 hr for TAK-044 and 1 hr for BQ-123 at 10 mg/kg. A selective ETB agonist, sarafotoxin S6c (0.3 nmol/kg i.v.), induced both depressor and pressor responses similar to ET-1. The initial depressor response was inhibited by TAK-044 in a dose-dependent manner (0.1-10 mg/kg i.v.) and by BQ-123 at the highest dose, whereas the sustained pressor response was inhibited only by TAK-044 at a dose of 10 mg/kg. Similar differences between TAK-044 and BQ-123 were observed for sarafotoxin S6c-induced renal vasoconstriction: TAK-044 but not BQ-123 inhibited the response at a dose of 3 mg/kg i.v. We conclude that TAK-044 inhibited both ETA- and ETB-mediated blood pressure responses and that these effects were longer lasting than those of BQ-123. In addition, the ETB-mediated vasoconstriction and pressor responses were inhibited by TAK-044 and not by BQ-123.

Animals↗