PubMed HealthSearch

Biomedical subjects

S Hamano

Publications and source records attributed to S Hamano.

At least 19 recordsLinked to original sources

Study of low molecular weight heparin effect on the relation between anticoagulant activity and antithrombin III affinity.

Low molecular weight heparin (FR-860), and conventional unfractionated heparin (UF-heparin) were fractionated by rabbit antithrombin III (AT III)-Sepharose, and the effects of each affinity fraction on the coagulation and fibrinolytic activities were investigated. FR-860 was fractionated to no-affinity, low-affinity (LA) and high-affinity (HA) fractions, and UF-heparin to LA and HA fractions. The HA fractions showed higher activities regarding the prolongation of activated partial thromboplastin time, anti-factor Xa activity and antithrombin activity compared with those of LA. The HA and LA fractions exhibited the enhancement of heparin cofactor II (HC II) activity and fibrinolytic activity in a dose-dependent manner. These results suggest that the antithrombotic activity of FR-860 is exerted through AT III and other mechanism such as HC II-mediated system.

Animals

Study of anticoagulant mechanism of low molecular weight heparin.

The binding ability of low molecular weight heparin (FR-860), and conventional unfractionated heparin (UF-heparin) to factor Xa (F.Xa), thrombin and AT III was investigated using FR-860- and UF-heparin-Sepharoses. FR-860 could not bind directly to F.Xa. FR-860 bound to thrombin and AT III with stronger affinity to AT III than to thrombin. On the other hand, UF-heparin bound to F.Xa, thrombin and AT III with the strongest affinity to AT III followed by thrombin and F.Xa. AT III mediated the binding between F.Xa and FR-860 and accelerated the reaction between F.Xa and UF-heparin. On the other hand, AT III did not affect the binding between thrombin and FR-860 or UF-heparin. Diisopropyl fluorophosphate-treated thrombin inhibited the binding between AT III and FR-860, but not that between AT III and UF-heparin. These results suggest that the anti-F.Xa activity of FR-860 is mediated by AT III. Furthermore, the difference of antithrombin activity between FR-860 and UF-heparin depends on the capability to form ternary complex of FR-860 or UF-heparin, AT III and thrombin.

Animals

Developmental changes in the incidence of chromosome anomalies of bovine embryos fertilized in vitro.

In total, 196 two- to 32-cell bovine embryo and 104 blastocysts were obtained by the in vitro fertilization of follicular oocytes matured in vitro, and 15 blastocysts fertilized in vivo were used. Chromosomal anomalies in these embryos and the inner cell mass (ICM) separated immunologically were investigated. Chromosomal anomalies were observed in 12.1% (5/41) of 2-cell embryos, 20.0-36.4% of 4- to 16-cell embryos, 7.1% (1/14) of 17- to 32-cell embryos, 44.2% (15/34) of blastocysts, and 18.6% (13/70) of ICM cells derived from in vitro fertilization. These anomalies were mainly 3N and 4N at 2-cell stage, 1N and 1N/2N at 4- to 32-cell stages, and 2N/4N in blastocysts and in their ICM cells. Chromosomal anomalies of blastocysts from in vivo fertilization and their ICM were observed in 20.0% (1/5) of blastocysts and 33.3% (3/9) of ICM cells and these compositions were mainly 2N/4N. These results indicate that the abnormalities at early and blastocyst stages of embryos derived from in vitro fertilization were caused by abnormal fertilization in vitro and abnormal cleavage, respectively. Furthermore, a definite location of the chromosomal anomalies was observed in the trophectoderm of blastocysts derived from in vitro fertilization.

Animals

Treatment of early recurrent medulloblastoma in children with cisplatin and etoposide: a preliminary report.

The prognosis of recurrent medulloblastoma remains extremely poor. Combination chemotherapy with cisplatin (CDDP) and etoposide (VP-16) was given to five children with early recurrent medulloblastoma. As a rule, CDDP 20 mg/m2 per day and VP-16 60 mg/m2 per day were administered intravenously for 5 days. This cycle was repeated three times at 4-week intervals. After this therapy, cerebellar signs improved in one case and were unchanged in four cases. Weakness and sensory disturbance, however, improved in three of four patients. Moreover, neck and/or back pain resolved in all these four. Radiological findings improved in three cases. Myelosuppression appeared in all patients, but receded rapidly. No other significant complications were noticed. Two patients died 5 and 6 months after this therapy. These results seem to suggest that this therapy has a use in improving neurological symptoms, particularly neck and/or back pain, although its efficacy is limited.

Adolescent

Novel eosinophilic inclusion in astrocytes.

Intracytoplasmic and brightly eosinophilic inclusions within neuroglias are reported in a patient with Aicardi's syndrome. Most inclusion-bearing neuroglias were protoplasmic astrocytes in the cerebral cortex. Compared with similar eosinophilic and intracytoplasmic inclusions in other studies using both light and electron microscopy, the inclusions in this report are regarded as being novel and not previously described. Ultrastructurally, the inclusions were composed of electron-dense granules and amorphous substances, and were not surrounded by a limiting membrane. They were numerous in the cerebral cortex, especially in part of the microgyrus, but absent in the deep cerebral white matter, subcortical nuclei, brain stem and the cerebellum. Therefore, they may be closely associated with brain malformation and congenital astrocytic dysfunction. They also suggested a functional difference in protoplasmic astrocytes themselves, according to the differentiation of related gray matter.

Agenesis of Corpus Callosum

Further studies on the relationship between tyrosine supply and catecholamine production in cultured adrenal chromaffin cells.

To elucidate a possible role of tyrosine supply as a factor modulating catecholamine biosynthesis in the adrenergic cell, the transport of [14C]tyrosine into cultured bovine adrenal chromaffin cells was first examined, and the relationship between [14C]tyrosine transport and [14C]catecholamine formation was then investigated. Under the conditions which were routinely employed to determine the rate of catecholamine biosynthesis, tyrosine was taken up into the cells in a manner independent of extracellular Na+ and Ca2+, and this uptake was also insensitive to ouabain and various metabolic inhibitors. The stimulation of these cells with high K+ and other secretagogues caused no significant alteration in the uptake. While, tyrosine transport was markedly inhibited by tyrosine analogues and other L-aromatic amino acids, and this inhibition was accompanied by the reduction of [14C]catecholamine formation. In contrast, tyrosine transport was markedly enhanced by flavone, and this enhancement was also accompanied by the augmentation of catecholamine production under the same experimental conditions. These results seem to indicate that the transport of tyrosine into the cells may be closely related to catecholamine formation within the cells, thus providing an evidence for a possible role of tyrosine supply as one of the factors affecting catecholamine production in the adrenal chromaffin cell.

Adrenal Medulla

Synthesis and cardiovascular activity of phenylalkylamine derivatives. I. Potential specific bradycardic agents.

A series of acyclic amide derivatives of N-(omega-aminoalkyl)-N-methylhomoveratrylamine was synthesized and evaluated for their bradycardic activity in isolated guinea pig right atria. Among these compounds, (E)-N-[3-[N'-[2-(3,4-dimethoxyphenyl)ethyl]-N'-methylamino]propyl]- 4-[3,4-(methylenedioxy)phenyl]-3-butenamide (35) was the most potent in vitro and was also found to show dose-dependent bradycardia without remarkable reduction of left ventricular dp/dtmax or mean aortic pressure in anesthetized dogs.

Animals

[Effect of tranilast, an anti-allergic drug, on the human keloid tissues].

We studied the inhibitory effects of tranilast, an anti-allergic drug, on the human keloid tissues implanted into the dorsal skin of athymic nude mice and on the growth of keloid fibroblast in vitro. In the keloid tissue-implanted model, tranilast (50-200 mg/kg, p.o.) decreased the weight of the keloid tissue as triamcinolone (25 mg/kg, p.o.) did. Tranilast (200 mg/kg, p.o.) reduced the hydroxyproline content of implanted tissues. Tranilast (3-300 microM) also inhibited the collagen synthesis by keloid fibroblast in vitro. Only a high concentration of tranilast (300 microM) suppressed the glycosaminoglycan synthesis and cell proliferation of keloid fibroblasts. Moreover, tranilast scarcely affected the fibronectin production. Triamcinolone (10 microM) also inhibited glycosaminoglycan synthesis and cell proliferation. These results suggest that the inhibitory effect of tranilast on the keloid tissues is related to its inhibition of the collagen synthesis of fibroblasts. Tranilast would be useful as a therapeutic drug for the treatment of keloids.

Animals

[Effect of tranilast, an anti-allergic drug, on carrageenin-induced granulation and capillary permeability in rats].

We studied the effect of tranilast on the growth of carrageenin-induced granulation and the increase in capillary permeability induced by inflammatory agents in rats. In the carrageenin-induced granulation model, tranilast (50 or 100-200 mg/kg, p.o.) decreased significantly and dose-dependently the weight and the hydroxyproline content of the granulation tissue. Tranilast, however, showed no effect on the healing day of locally wounded dorsal skin of rats. Triamcinolone (10 mg/kg, p.o.) also showed an inhibitory effect on the carrageenin-induced granulation model. Tranilast (50-400 mg/kg, p.o.) dose-dependently inhibited the enhancement of capillary permeability induced by the Ca ionophore A23187, bradykinin and xanthine oxidase. Moreover, tranilast (30 and 300 microM) suppressed superoxide production induced by FMLP in human neutrophils, but did not act as a superoxide scavenger. Considering that hypertrophic scar and keloid are conditions characterized by abnormal cell proliferation and excessive collagen accumulation accompanied with itch and pain, these results suggest that tranilast is useful as a therapeutic drug for hypertrophic scars and keloids.

Adult

Vitrification of bovine blastocysts obtained by in vitro culture of oocytes matured and fertilized in vitro.

Two experiments were conducted to assess the viability of bovine blastocysts obtained by in vitro fertilization of oocytes matured in vitro (IVM-IVF) and cryopreserved by vitrification. In Expt 1, the optimal concentrations of glycerol and 1,2-propanediol in the basic medium (modified TCM199) for cooling and warming without formation of ice crystals were determined by plunging the solution into liquid nitrogen and then warming it in a water bath at 15 degrees C; when both glycerol and 1,2-propanediol were present in the solution (> 45% v/v), vitrification of the medium was observed. In Expt 2, IVM-IVF blastocysts were equilibrated to the mixture of glycerol and 1,2-propanediol (0% to 45%) at 15 degrees C in a stepwise manner as follows: (i) in one step, for 18 min to the final vitrification solution; (ii) in two steps, for 8 min in the first step and 10 min in the second step; (iii) in four steps, for 4 min in the first three steps and 6 min in the last step; (iv) in eight steps, for 2 min in each step, but 4 min in the last step; and (v) in 16 steps, for 1 min in each step, but 3 min in the last step. After removal of cryoprotectants, the blastocysts were cultured for 24 h in vitro. The survival rates for the embryos equilibrated in 1, 2, 4, 8 and 16 step(s) were 56, 89, 100, 100 and 100%, respectively. The blastocysts equilibrated in 1, 2, 4, 8 and 16 steps were vitrified by plunging the straws containing them into liquid N2, thawed and cultured in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Inhibition by amiloride of ouabain-evoked catecholamine secretion from cultured adrenal chromaffin cells: evidence for its blocking action on interaction between ouabain and Na+/K(+)-pump.

The effect of amiloride on ouabain-evoked catecholamine secretion was investigated in primary cultures of bovine adrenal chromaffin cells. Catecholamine secretion evoked by ouabain was inhibited markedly by amiloride, but the secretion evoked by Na+ removal was not affected by the drug. In contrast, adriamycin, a putative inhibitor of the Na(+)-Ca++ exchange, inhibited the secretion evoked by Na+ removal as well as that evoked by ouabain. The inhibitory action of amiloride on the ouabain-evoked secretion was therefore considered to be due to its action on other mechanism(s) than the Na(+)-Ca++ exchange process. Further studies showed that the uptake of 86Rb+ into the cells was slightly but significantly reduced by amiloride, and the inhibitory action of ouabain on 86Rb+ uptake was considerably blocked by this drug under the experimental conditions in which the inhibition of ouabain-evoked secretion was observed. The binding of [3H] ouabain to the intact cells was also inhibited by amiloride under the same conditions. These results suggest that amiloride may inhibit ouabain-evoked catecholamine secretion as a consequence of blocking the inhibitory action of ouabain on the plasma membrane Na+/K(+)-pump in adrenal chromaffin cells.

Adrenal Medulla

[Proposal of a new classification of adult bronchial asthma--child onset asthma, adult onset asthma and adult relapse asthma. Project Team for Research into Adult Bronchial Asthma in Japan].

The first nationwide research into adult bronchial asthma in Japan proposed a new classification of adult asthma. Adult asthma was categorized into child onset asthma, adult onset asthma and adult relapse asthma. The frequency of child onset asthma, adult onset asthma and adult relapse asthma in adult asthma was 11.2%, 77.3% and 3.7%, respectively. The frequency of child onset asthma decreased markedly in the older age group. On the other hand, the frequency of adult onset asthma increased, and reached more than 90%, in the older age group. The frequency of the following factors: atopic asthma, complications with other atopic diseases, mild asthma, male patients, experience of mechanical ventilation, visits to night clinics and oxygen therapy on acute attack, was significantly higher in the child onset asthma group than in the adult onset asthma group. The frequency of infectious type, aspirin intolerance, steroid dependent asthma, severe asthma and regular medication was significantly higher in the adult onset asthma group. Adult relapse asthma seemed to fall between these two groups. Based on the above observations, we proposed a new classification of adult asthma which includes child onset asthma, adult onset asthma and adult relapse asthma.

Asthma

[Neurological manifestations in hemorrhagic colitis associated with Escherichia coli O 157: H 7].

From September through November 1990, an outbreak of hemorrhagic colitis associated with Escherichia coli O 157: H 7, occurred in a kindergarten in Saitama, Japan. Some of the patients suffered from neurological symptoms such as stupor, deep coma and/or convulsions in the acute stage, and/or action tremors, nystagmus, incontinence, phrenic nerve palsy in the later stage. Serum complements decreased more in the patients with neurological symptoms than in the patients without them. The verotoxin elaborated by E. coli O 157: H 7 was considered to cause the neurological symptoms, on the basis of their clinical courses and laboratory findings, especially the cerebrospinal fluid findings.

Child

Development of the human dorsal nucleus of vagus nerve: a morphometric study.

The development of the human dorsal nucleus of the vagus nerve was studied on serial sections of the brain of 10 fetuses at 16-40 weeks of gestation, an infant at 2 months of age and an adult of 63 years. A morphometric analysis revealed that the nucleus is divided into three subnuclei (caudal, dorsal and ventral) and that this subdivision is maintained from 16 weeks of gestation to adulthood. The early development of the nucleus is gradual between 16 and 40 weeks of gestation without the rapid growth phase apparent with the motor trigeminal, hypoglossal and facial nuclei.

Brain

Synthesis and biological evaluation of substituted benzenesulfonamides as novel potent membrane-bound phospholipase A2 inhibitors.

A novel series of 4-[N-methyl-N-[(E)-3-[4-(methylsulfonyl)phenyl]-2- propenoyl]amino]benzenesulfonamides has been prepared and evaluated as membrane-bound phospholipase A2 inhibitors. A structure-activity relationship study indicated that the optimum potency was realized with the N-(phenylalkyl)piperidine derivatives 3 and 4. These compounds inhibited the liberation of arachidonic acid from the rabbit heart membrane fraction with IC30 values of 0.028 and 0.009 microM, respectively. Several compounds (3, 4, and 28), which proved to be potent inhibitors in vitro, significantly reduced the size of myocardial infarction in coronary occluded rats by iv administrations prior to the ligation. N-(1-Benzyl-4-piperidinyl)-4-[N-methyl-N-[(E)-3-[ 4-(methylsulfonyl)phenyl]-2-propenoyl]amino]-benzenesulfonamide (3, ER-3826), which showed the protective in vivo effects at doses higher than 0.3 mg/kg iv, was finally chosen as a leading candidate.

Animals

[Effects of low molecular weight heparin (FR-860) on the experimental disseminated intravascular coagulation models].

Effects of low molecular weight heparin (FR-860) on experimental disseminated intravascular coagulation (DIC) models in rats were compared with those of conventional unfractionated heparin (UF-heparin) and other anticoagulants. In the endotoxin-induced DIC model, FR-860 (12.5-200 U/kg/hr) and UF-heparin (25-200 U/kg/hr) inhibited dose-dependently the decreases in platelet counts, fibrinogen, antithrombin III activity and alpha 2-plasmin inhibitor activity, and they also inhibited the increases in fibrin de-products and thrombus formation in the glomerular capillary bed. Neither gabexate mesilate (FOY, 10 mg/kg/hr) nor nafamostat mesilate (FUT, 0.1 mg/kg/hr) improved endotoxin-induced DIC. FR-860 showed comparable potency to UF-heparin in plasma anti-factor Xa (F.Xa) activity. However, FR-860 was weaker than UF-heparin in prolongation of activated partial thromboplastin time. In the thrombin-induced DIC model, both FR-860 and UF-heparin significantly improved, as seen in the endotoxin-induced DIC model, the changes in coagulation and fibrinolytic parameters and suppressed the production of pulmonary thrombus. On the other hand, both FOY and FUT showed significant but weak improvement in this model. In addition, FR-860 inhibited the enhancement of fibrinolysis and the production of pulmonary thrombus in the lactic acid-induced DIC model. These results suggest that the efficacy of FR-860 on DIC in rats is comparable to that of UF-heparin and that the efficacy can be attributed to its anti-F.Xa activity. FR-860 can be expected to be a useful therapeutic drug for DIC.

Animals

Pharmacological study on Ba2(+)-stimulated catecholamine secretion from cultured bovine adrenal chromaffin cells: possible relation of Ba2+ action to Ca(2+)-activated secretory mechanism.

The stimulatory action of Ba2+ on catecholamine secretion from cultured bovine adrenal chromaffin cells was studied to elucidate a possible relationship between Ba2+ action and the Ca2(+)-mediated secretory mechanism. Catecholamine secretion was dramatically stimulated by Ba2+ in the absence of external Ca2+, and this stimulatory action was observed in a concentration-dependent manner. Ba2+ evoked the concomitant release of dopamine beta-hydroxylase in a similar manner to the Ca2(+)-dependent secretion. The stimulation of catecholamine secretion by low concentrations of Ba2+ was markedly inhibited by protein kinase inhibitors, polymyxin B and trifluoperazine (TFP). The inhibitory action of polymyxin B, but not that of TFP, on the Ba2+ action was attenuated by elevating the concentration of Ba2+ in the incubation mixture. The stimulatory action of Ba2+ was enhanced by a protein kinase C activator, 12-O-tetradecanoylphorbol 13-acetate (TPA). In contrast to the acute effect of TPA, chronic exposure of chromaffin cells to high concentration of TPA reduced catecholamine secretion stimulated by Ba2+ as well as high K+ and carbamylcholine. These findings suggest the possibility that Ba2+ may activate Ca2(+)-mediated secretory processes presumably through its action on protein kinase C, thus resulting in the stimulation of catecholamine secretion from bovine adrenal chromaffin cells.

Adrenal Medulla