Y Hara

Nippon Veterinary and Animal Science University, Edo, Tōkyō, Japan

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Publications (22)24.36 Total impact

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    ABSTRACT: Abstract— The mechanism of endothelium-dependent relaxation induced by pirarubicin, (2″R)-4′-O-tetrahydropyranyladriamycin, THP, or carbachol was investigated in the rat isolated aorta. The relaxant effect of THP (1·5 × 10−6-4·5 × 10−5m) or carbachol (10−8-10−4m) on the aorta with endothelium was decreased by lowering Ca2+ in the medium. The relaxation induced by THP was not inhibited by pretreatment with verapamil (10−6–10−5m), and that induced by carbachol was only partially inhibited. However, on replacement of all but 20 Mm Na+ with either Li+ or choline, the THP- or carbachol-induced relaxation was inhibited. Furthermore, the relaxing effect of THP or carbachol was inhibited by pretreatment with amiloride (10−4-3 × 10−4m), with ouabain (10−4-10−3m), or with K+-depletion. These results suggest that the THP- or carbachol-induced relaxation depending on endothelium was affected by modifying the calcium ion concentration, and that a Na+–Ca2+ exchange process is involved.
    Journal of Pharmacy and Pharmacology. 04/2011; 44(3):244 - 249.
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    ABSTRACT: Effect of recombinant human basic fibroblast growth factor (bFGF) on fracture healing was investigated using a tibial fracture in beagle dogs. Transverse fractures in the middle of the diaphyses were created in the right tibiae and bFGF was injected into the fracture sites at a single dose of 200 micrograms. The time course of changes in callus volume and morphology of the fracture sites were evaluated at weeks 2, 4, 8, 16, and 32 after treatment, and the fracture strength was analyzed at weeks 16 and 32. At week 2, a radiogram of the fracture site showed obvious membranous ossification in the group injected with bFGF. Basic FGF extended the callus area at week 4 and increased the bone mineral content (BMC) in the callus at week 8. bFGF also increased the osteoclast number in the periosteal callus at weeks 2 and 4. In the bFGF group, a maximal increase in the osteoclast index was found at week 4, and an identical increase was recognized in the control group at weeks 8 and 16. These findings strongly suggested that bFGF stimulated not only callus formation but osteoclastic callus resorption. BMC in the bFGF group was followed by a rapid decrease from week 8, while that in the control group was identical from week 4. Fracture strength of the bFGF group showed significant recovery by week 16, and recovery was still evident by week 32. We conclude that bFGF promotes the fracture healing in dogs by the stimulation of bone remodeling.
    Journal of Bone and Mineral Research 07/1998; 13(6):942-9. · 6.13 Impact Factor
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    ABSTRACT: Poly(L-lactide) (PLLA) was molded into films and rods, and drawn in the longitudinal direction to endow them with piezoelectricity. The piezoelectric constants of PLLA films increased with the draw ratio and, after passing a maximum at a draw ratio around 5, decreased. PLLA samples with a draw ratio 5 underwent fibrilization. The PLLA rods were intramedullarily implanted in the cut tibiae of cats for internal fixation up to 8 weeks. Fracture healing was clearly promoted with increased callus formation as the draw ratio of the PLLA rod increased, whereas the undrawn PLLA as well as a polyethylene control rod had no effect on callus formation, or rather, retarded it. This finding strongly suggests that the promotion of fracture healing by fixation with drawn PLLA can be ascribed to the piezoelectric current generated by the strains accompanying leg movement.
    Journal of Biomedical Materials Research 05/1996; 30(4):553-8.
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    ABSTRACT: Surgical removal of an intrathoracic tumor derived from a vagus nerve was undergone in a dog with hypertrophic osteopathy. The tumor was pathologically diagnosed as malignant schwanoma. Soft tissue swelling, lameness, and itchiness in four limbs disappeared within 7 days after surgery. The proliferated periosteal osteophytes of the four limbs was progressively reduced with time by follow-up radiography on the 58th day after surgery. On the 710th day after surgery, these osteophytes were greatly decreased as osteopathy, malignant schwanoma.
    Journal of Veterinary Medical Science 03/1995; 57(1):133-5. · 0.88 Impact Factor
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    ABSTRACT: This study was undertaken to evaluate the sedative effect of medetomidine, an alpha 2-adrenoceptor agonist, and the counteractive effect of atipamezole, an antagonist to medetomidine, in house musk shrews (Suncus murinus). Two hundred, 300, 400, or 600 micrograms/kg of medetomidine was intraperitoneal injected into 89 house musk shrews. A sedative effect was produced in one to two minutes after injection. The dose-dependent prolongation of the sedative duration and the dose-dependent appearance of a hypothermic effect were demonstrated. With 200 micrograms/kg of medetomidine, the sedative effect obtained was not adequate in some of the animals. With 300 micrograms/kg and above, a stable sedative state was induced in all the animals. The duration of sedation in the house musk shrews was much longer (p < 0.01) in males than in females. This suggested the higher susceptibility of male house musk shrews to this drug. The sedative effect and hypothermia obtained with 400 micrograms/kg of medetomidine were completely counteracted by more than 2.0 mg/kg of atipamezole. With 0.5 and 1.0 mg/kg of atipamezole, only a partial antagonistic action was produced. Transient vomiting appeared in 4.5% of the house musk shrews at approximately one minute after injection of medetomidine. This side-effect had occurred before the sedative effect was obtained, and was not serious enough to be a problem. None of the 89 house musk shrews died in this experiment. The above results show that the combination of medetomidine and atipamezole is a highly effective and safe anesthetic treatment which permits easy handling of house musk shrews.
    Experimental Animals 02/1995; 44(1):49-55. · 1.46 Impact Factor
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    ABSTRACT: Transverse diaphyseal fractures of the femur were experimentally made in immature cats, and were fixed by an intramedullary pinning technique using an uniaxially oriented poly-L-lactide (PLLA) rod, a biodegradable polymer. The healing process was evaluated radiographically and histologically. Formation of bony callus was completed in 8 weeks, and cortical bony union followed. The remodeling process was then observed form 12 to 16 weeks. The healing process was almost the same as when a metallic implant was used. Abundant periosteal callus formation may be attributable to the lower elasticity of the PLLA rod compared with metallic implants. Since no other abnormalities such as growth deformities were detected, it was concluded that the combined use of a uniaxially oriented PLLA rod and an external splint is clinically useful for the repair of diaphyseal fractures in immature cats.
    Journal of Veterinary Medical Science 01/1995; 56(6):1041-5. · 0.88 Impact Factor
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    ABSTRACT: The clinical usefulness of biodegradable oriented poly-L-lactide (PLLA) screws for experimental Salter-Harris type 4 fracture in the distal femoral condyle of dogs was evaluated. Bony union of the osteotomized fragment of the condyle was almost completed radiographically and histologically within 1 to 2 months after surgery, suggesting that PLLA screws maintained strength long enough to fix the fragment until bone healing. At 4 to 6 months after surgery, minute fissures were histologically confirmed on the surface of the screw thread, suggesting the early stage of biodegradation and absorption of the polymer. During the observational period, no significant difference between the treated femur and the contralateral non-treated femur in either total femoral length or maximum condyle width was observed, indicating no growth disturbance in the treated femur. From these results it was concluded that the PLLA screw might be an ideal implant for the reduction and fixation of epiphyseal plate fractures such as Salter-Harris type 3 or type 4 fractures.
    Journal of Veterinary Medical Science 11/1994; 56(5):817-22. · 0.88 Impact Factor
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    ABSTRACT: In order to examine the prophylactic effects of milbemycin oxime (MO) against Dirofilaria immitis infection, experiments were carried out under multiple infection with D. immitis. Ten filaria-free beagles of age 4 to 8 months were each inoculated with a total number of 480 larvae 12 times at intervals of 15 days over a period of 6 months, and MO was given monthly for the 6 months at a dose of 0.25 mg/kg. The infection rate in the medicated group of dogs was nil, this suggesting complete protection of the infection, while in the non-medicated control group it ranged from 6.5 to 14.8% (mean, 11.4%).
    Journal of Veterinary Medical Science 09/1994; 56(4):779-80. · 0.88 Impact Factor
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    ABSTRACT: Computed tomography after myelography (CTM) was performed pre- and postoperatively on four dogs diagnosed as having cervical intervertebral disc protrusion. The surgery was performed by ventral slot technique in all the cases. The direction of the ventral slot was precisely adjusted according to the location of the protruded discs as seen on CTM. Postoperative values for the transversal area of the spinal cord were greater than those measured preoperatively, suggesting effective decompression of the cord. The prognosis for these patients was excellent. In view of these results, it was considered that preoperative confirmation of the positional relationship between the spinal cord and the protruded disc by CTM was quite useful in planning the surgical technique for disc disease in the dog.
    Journal of Veterinary Medical Science 09/1994; 56(4):791-4. · 0.88 Impact Factor
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    ABSTRACT: A shock model was experimentally produced by intravenous injection of a lethal dose (3 mg/kg) of endotoxin under general anesthesia induced by pentobarbital sodium using 7 beagles. The effect of this endotoxic shock on the reticuloendothelial function was investigated. The blood endotoxin concentration peaked immediately after administration and decreased subsequently. However, the value still remained on an increased level (1,051 pg/ml) even at 360 min after endotoxin treatment. The lipid emulsion test as an index of reticuloendothelial phagocytotic activity and the arterial ketone body ratio as an index of the energy charge in the liver decreased after endotoxin treatment and failed to recover during the experiment. Fibronectin, one of opsonic proteins, tended to decrease after injection of the endotoxin and was significantly (p < 0.01) low at 180 and 360 min compared with the value before injection of the endotoxin. These results suggested the depression of the reticuloendothelial function during endotoxin-induced shock.
    Journal of Veterinary Medical Science 08/1993; 55(4):607-11. · 0.88 Impact Factor
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    ABSTRACT: Accuracy assessment was undertaken under varying hemodynamic conditions for a lung water volume measurement device which is based on the principle of a double indicator dilution method using heat and sodium ions. Changes in extravascular thermal volume were investigated in dogs with endotoxin-induced shock. The isoproterenol- or propranolol-induced changes in hemodynamics had no effect on the measurement. This confirmed the high accuracy of this measuring method. The measurement revealed a tendency for the extravascular thermal volume to gradually increase (p < 0.05) during endotoxin shock. This confirmed the gradual progression of pulmonary edema during endotoxin shock.
    Journal of Veterinary Medical Science 03/1993; 55(1):87-91. · 0.88 Impact Factor
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    ABSTRACT: The inhibitory effect of tiamulin, an antibiotic produced by Pleurotus mutilis, on contractile and electrical responses in isolated thoracic aorta and cardiac muscle of guinea-pigs was studied. In the thoracic aorta, tiamulin with an IC50 of 9.7 x 10(-6) M inhibited sustained contractions induced by isosmotically added 60 mM KCl. The inhibitory effect of tiamulin on a Ca(2+)-induced contraction in a depolarized muscle was competitively antagonized by raising external Ca2+ concentration. Bay K 8644 (10(-7) M) antagonized tiamulin's inhibition of the Ca(2+)-induced contraction. Tiamulin (2 x 10(-5) M) decreased the elevated cytoplasmic Ca2+ level measured by the fura 2 AM method in the depolarized muscle. In high K(+)-isoprenaline-treated left atria, tiamulin (2 x 10(-5)-2 x 10(-4) M) produced negative inotropic effects. On the other hand in the membrane action potential of papillary muscles, tiamulin (2 x 10(-6)-2 x 10(-4) M) produced decreases in action potential and durations and 2 x 10(-4) M tiamulin depressed the slow response action potential in depolarized muscles. Tiamulin produced prolongations of the PR interval in ECG, negative chrono- and inotropic effects, and an increase in perfusion flow in guinea-pig isolated and perfused hearts. These effects of tiamulin on the aorta or cardiac muscle were similar to those of verapamil and nifedipine. These results suggest that both the inhibitory action of tiamulin on the high K(+)-induced contraction in the aorta and the negative inotropic effect of tiamulin on the cardiac muscle are due to an inhibition of Ca2+ entry through the voltage-dependent Ca2+ channels of cells of both these muscles.
    Journal of Pharmacy and Pharmacology 10/1992; 44(9):731-6. · 2.03 Impact Factor
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    ABSTRACT: The mechanism of endothelium-dependent relaxation induced by pirarubicin, (2''R)-4'-O-tetrahydropyranyladriamycin, THP, or carbachol was investigated in the rat isolated aorta. The relaxant effect of THP (1.5 x 10(-6)-4.5 x 10(-5) M) or carbachol (10(-8)-10(-4) M) on the aorta with endothelium was decreased by lowering Ca2+ in the medium. The relaxation induced by THP was not inhibited by pretreatment with verapamil (10(-6)-10(-5) M), and that induced by carbachol was only partially inhibited. However, on replacement of all but 20 mM Na+ with either Li+ or choline, the THP- or carbachol-induced relaxation was inhibited. Furthermore, the relaxing effect of THP or carbachol was inhibited by pretreatment with amiloride (10(-4)-3 x 10(-4) M), with ouabain (10(-4)-10(-3) M), or with K(+)-depletion. These results suggest that the THP- or carbachol-induced relaxation depending on endothelium was affected by modifying the calcium ion concentration, and that a Na(+)-Ca2+ exchange process is involved.
    Journal of Pharmacy and Pharmacology 04/1992; 44(3):244-9. · 2.03 Impact Factor
  • Journal of Veterinary Medical Science 03/1992; 54(1):181-4. · 0.88 Impact Factor
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    ABSTRACT: Tiamulin with an IC50 of 1.7 x 10(-6) M inhibited both the rapid and sustained contractions induced by hyperosmotically added 60 mM K+ (Hyper 60 K+) without changing the membrane potential in the intestinal muscle. Tiamulin inhibition (2 x 10(-6)-2 x 10(-5) M) of the Ca(2+)-induced contraction in depolarized muscle was competitively antagonized by raising external Ca2+. Tiamulin (2 x 10(-5) M) slightly affected the Hyper 60 K(+)-induced phasic contraction under hypoxia and the carbachol-induced phasic contraction. Moreover, tiamulin (2 x 10(-5) M) inhibited the Hyper 60 K(+)-induced contraction with decreasing [Ca2+]cyt level. Although the inhibitory effect of 10(-7)-10(-5) M monesin, an inhibitor of mitochondrial respiration, on the Hyper 60 K(+)-induced contraction was reduced under hypoxia, the effect of tiamulin (2 x 10(-7)-2 x 10(-4) M) was not modified. Tiamulin changed neither the intracellular Na+ and K+ content of the depolarized muscle nor the Ca(2+)-induced contraction in the chemically skinned preparations. These results suggest that the inhibitory action of tiamulin on the Hyper 60 K(+)-induced tonic contraction is possibly due to the competitive inhibition of Ca2+ entry through the voltage-dependent Ca2+ channel of the intestinal smooth muscle cell.
    The Japanese Journal of Pharmacology 01/1992; 57(4):591-600.
  • Journal of Veterinary Medical Science 01/1992; 53(6):1105-7. · 0.88 Impact Factor
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    ABSTRACT: The mechanism of relaxation produced by pirarubicin [(2"R)-4'-O-tetrahydropyranyladriamycin, THP] has been studied in rat isolated aorta. THP (1.5 x 10(-6)-4.5 x 10(-5) M) markedly relaxed contractions induced by noradrenaline (10(-7) M) in the aorta with endothelium, but not in that without endothelium. The relaxation induced by 1.5 x 10(-5) M THP was inhibited by methylene blue (5 x 10(-6) M), hydroquinone (10(-4) M), phenidone (5 x 10(-5) M), haemoglobin (10(-6) M) and p-bromophenacyl bromide (5 x 10(-5) M), but not by indomethacin (2.5 x 10(-5) M). The relaxation induced by THP (1.5 x 10(-7) -4.5 x 10(-5) M) was inhibited by NG-nitro-L-arginine (10(-5) M), but enhanced by superoxide dismutase (10 units mL-1) or by L-arginine (10(-2) M). However, the THP-induced relaxation was not inhibited by various receptor antagonists such as atropine (10(-6) M), cimetidine (10(-5) M), diphenhydramine (3 x 10(-6) M) and [D-Pro4, D-Trp7,9,10]-substance P(4-11) (1.5 x 10(-6) M). In fifteen anthracycline analogues, THP and 13-dihydropirarubicin (both with a tetrahydropyranyl group) produced endothelium-dependent relaxations. These results suggest that the THP-induced relaxation which is probably mediated by endothelium-derived relaxing factor (EDRF) was not produced by an activation of muscarine, histamine H1 or H2, or substance P receptor, and further that the tetrahydropyranyl group must play an important role in the THP-induced relaxation.
    Journal of Pharmacy and Pharmacology 01/1992; 43(12):848-54. · 2.03 Impact Factor
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    ABSTRACT: In the present study we examined the effects of pirarubicin [(2"R)-4'-O-tetrahydropyranyladriamycin, THP] on a cardiovascular system. An injection of THP (0.39-3.13 mg/kg, i.v.) reduced the mean blood pressure and caused an increase in the respiratory air rate in anesthetized rats. At 1.5 x 10(-6)-1.5 x 10(-5) M, THP markedly relaxed a contraction induced by 10(-7) M norepinephrine in rat aorta with endothelium but not in that without endothelium. At a dose of 0.02-0.5 mg, THP produced an increase in the contractile force and the perfusion flow of isolated perfused guinea pig hearts. At a higher concentration (4.5 x 10(-5)-1.5 x 10(-4) M), it produced a slight increase in the contractile force of the left atria in guinea pigs. This positive inotropic action of THP was inhibited by diphenhydramine (10(-6)-5 x 10(-5) M), chlorpheniramine (3 x 10(-7)-3 x 10(-5) M), and tripelennamine (3 x 10(-7)-3 x 10(-5) M) but not by propranolol (10(-6) M), cimetidine (10(-5) M), diltiazem (10(-6) M), or ryanodine (10(-8) M). THP given i.v. at 2.5 mg/kg elevated the plasma histamine level in anesthetized dogs. From these data, we conclude that THP mainly relaxed the rat aorta in the presence of endothelium and that at higher concentrations, it increased the contractile force in the cardiac muscle, probably mediated through the release of histamine.
    Cancer Chemotherapy and Pharmacology 02/1991; 28(4):266-72. · 2.80 Impact Factor
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    ABSTRACT: A high titer of cytotoxic antibody against donor lymphocytes, tentatively designated as anti-F1, was found in one cat who received 3 times of skin allograft from the same donor. The anti-F1 antibody titer was 1:16, and the antibody activity was mostly detected in the IgG fraction. A cross-absorption test using erythrocytes from F1-positive animals revealed that the F1(+) antigen recognized by anti-F1 antibody was expressed on erythrocytes as well as lymphocytes. The frequencies of F1(+) and F1(-) types in 81 healthy cats, involving all the cats used for allo-immunization in the present study, were 30.9 and 69.1%, respectively. Moreover, F1 antigen was considered to be a hereditary antigen from family studies.
    Nippon juigaku zasshi. The Japanese journal of veterinary science 07/1990; 52(3):543-9.
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    ABSTRACT: The blastformation tests using concanavalin A and pokeweed mitogen were carried out on peripheral blood lymphocytes obtained from cats infected with feline immunodeficiency virus (FIV). The infected cats included those showing multiple chronic disease, those with a single mild sign, and one with no clinical sign. The infected cats showed significantly lower mitogenic responses of peripheral lymphocytes to both mitogens and lower lymphocyte counts as compared to uninfected healthy cats. These immunologic alterations in the infected cats may be closely related to the development of immunodeficiency-like disorders associated with FIV.
    Nippon juigaku zasshi. The Japanese journal of veterinary science 07/1990; 52(3):573-9.