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Biomedical subjects

H Fukasawa

Publications and source records attributed to H Fukasawa.

At least 73 records · Page 4Linked to original sources
PubMed1994

Development of posterior fossa dural sinuses, emissary veins, and jugular bulb: morphological and radiologic study.

PURPOSE: To report the anatomic and radiologic development of the transverse, sigmoid, and occipital sinuses, the emissary veins, and the jugular bulb formation from the jugular sinus in humans before and after birth. METHODS: Roentgenograms of 33 injected brains showing the cranial venous system in human fetuses from 3 to 7 months of gestational age and cerebral angiograms of newborns and infants up to 6 years of age (23 clinical cases) were made and analyzed in detail. Special attention was focused on the inner diameters of the transverse and sigmoid sinuses and of the internal jugular veins, particularly at the sigmoid sinus-internal jugular vein junction. RESULTS: Marked increase in venous flow from the rapidly growing cerebral hemispheres leads to ballooning of the transverse sinuses in the absence of an increase in the inner diameters of the sigmoid and jugular sinuses. The ballooning also results in formation of the occipital sinus, marginal sinus around the foramen magnum, and emissary veins. The formation of the jugular bulbs from the jugular sinuses begins after birth when a shift from a fetal to a postnatal type of circulation (or from a lying-down position to an erect posture) takes place. CONCLUSION: The morphological changes of the posterior fossa dural sinuses, emissary veins, and jugular bulb are closely related to the development of the brain, shift to postnatal type of circulation, and postural hemodynamic changes.

Cerebral Angiography↗
PubMed1994

Failure of normobaric oxygen therapy to reduce ischemic brain damage in rats.

We investigated the effects of 24-h oxygen therapy on focal cerebral ischemia in rats. Under halothane anesthesia, a 3-0 nylon thread was introduced into the neck internal carotid artery to occlude the left middle cerebral artery (MCA). Under atmospheric pressure, group 1 animals inhaled standard air; group 2, 40% O2; group 3, 60% O2; and group 4, 100% O2. Neuropathologic outcomes were quantified after a 24-h inhalation period. Infarct volumes tended to decrease in groups 2-4, but the decreases were not significant when compared with group 1. Hemispheric volume differences of groups 2-4 (27 +/- 18 mm3, 22 +/- 17 mm3, and 31 +/- 22 mm3, respectively) were less than that of group 1 (61 +/- 23 mm3, P < 0.05). Our results demonstrate that O2 therapy reduces brain swelling in rats 24 h after MCA occlusion. However, a dose-dependent decrease in brain swelling was not observed. In addition, we failed to see a significant decrease in the infarct size.

Animals↗
PubMed1993

Oxygenated cholesterols as ligands for cytosolic-nuclear tumor promoter binding protein: yakkasteroids.

Several oxygenated cholesterols and their derivatives (yakkasteroids) were prepared as candidate ligands for cytosolic-nuclear tumor promoter binding protein (CN-TPBP). Among the compounds, a possible natural substance, 3 beta,5 alpha-dihydroxycholestan-6-one (yakkasterone), showed the highest binding affinity to CN-TPBP. It also showed high specificity for binding to CN-TPBP: it does not bind to protein kinase C. Investigation of the structure-activity relationships of yakkasteroids revealed that the structure of the side chain at the 20-position is important for the binding activity to CN-TPBP.

Binding, Competitive↗
PubMed1993

Development of the Terumo Capiox centrifugal pump and its clinical application to open heart surgery: a comparative study with the roller pump.

We have developed the Terumo Capiox centrifugal pump (CXP), which consists of a rotor having a unique straight-path design to reduce pump rotational speed without decreasing hydraulic efficiency. The CXP was tested in vitro for blood trauma with a specially designed test circuit using fresh bovine blood. The Biopump (BP) (Medtronic, Minneapolis, MN, U.S.A.) and the roller pump (RP) were used as controls. The CXP demonstrated the smallest elevation of free plasma hemoglobin compared with the BP and the RP. The CXP was then applied to cardiopulmonary bypass (CPB) in 10 patients (CXP group) who underwent elective coronary artery bypass grafting (CABG), and the results were compared with those for a comparable roller pump group (RP group). Free plasma hemoglobin level, platelet count, and serum beta-thromboglobulin (beta-TG) level were measured during CPB. There were no CXP-related complications nor hemodynamic abnormalities during CPB. The CXP group demonstrated less hemolysis and less platelet depletion than the RP group. Furthermore, the serum beta-TG level was significantly lower in the CXP group than in the RP group. The CXP showed excellent hemodynamic performance with less blood trauma both in vitro and in clinical application to open heart surgery. Thus, the CXP has significant potential to be safely applied to CPB for open heart surgery and circulatory support.

Animals↗
PubMed1993

A straight path centrifugal blood pump concept in the Capiox centrifugal pump.

This article describes comparative studies of a newly developed "straight path" centrifugal pump (Capiox centrifugal pump) targeted for open-heart surgery and circulatory support. A unique straight path design of the rotor was very effective in reducing the pump's rotational speed and prime volume. This pump was evaluated for hydraulics, hemolysis, depriming characteristics, cavitation, and heat generation. Two commercially available centrifugal pumps, the Biomedicus cone-type pump and the Sarns 3M impeller-type pump, were used as controls. The new pump required the lowest pump speed to produce the same flow rates under the same pressure loads and demonstrated the lowest hemolysis and the lowest temperature rise with the outlet clamped. The air volume required to deprime the new pump was one-third to one-half that for the other pumps, and no sign of cavitation was observed even if a small amount of air was introduced to the pump inlet under a negative pressure of 200 mm Hg.

Animals↗
PubMed1993

AT-877, a Ca2+ antagonist, fails to reduce infarct size following rat middle-cerebral artery occlusion.

We investigated the effects of AT-877, a Ca2+ antagonist, on rat middle-cerebral artery occlusion. All rats had 6-h ischemia, and treated animals received either 3 or 10 mg/kg AT-877 s.c. just after the occlusion. Control animals received an equal volume of the vehicle. Prior to sacrifice, significant changes in the decrease of blood pressure and the increase of plasma glucose were observed in the treated rats. Although the infarct size tended to decrease, this decrease was not significant. Only when the blood pressure- or plasma glucose-matched subgroups were compared, the infarct volume decreased significantly in the drug-treated animals. Thus, AT-877 failed to reduce ischemic brain damage unless the blood pressure or plasma glucose were controlled.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1993

Expression of the ligand-binding domain-containing region of retinoic acid receptors alpha, beta and gamma in Escherichia coli and evaluation of ligand-binding selectivity.

The complete molecule or the ligand-binding domain-containing region of each of the three subtypes of human retinoic acid receptors (hRAR alpha, hRAR beta and hRAR gamma) was expressed in Escherichia coli. The expressed recombinant RARs (rRARs: rRAR alpha/E, rRAR beta/E and rRAR gamma) showed nearly the same magnitude of binding affinity toward [3H]retinoic acid (RA) as hRARs extracted from human cells (Ka values: 6.0 x 10(9) M-1 for rRAR alpha/E and 2.7 x 10(10) M-1 for both rRAR beta/E and rRAR gamma). Therefore, the ligand-binding selectivity of the rRARs toward RA and synthetic retinoids (4-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenylcarbamoyl )benzoic acid (Am80), (E)-4-[3-(3,5-di-tert-butylphenyl)-3-oxo-1-propenyl]benzoic acid (Ch55)) was examined. Am80 bound rRAR alpha/E preferentially and showed no binding activity toward rRAR gamma, which is consistent with the case of hRAR gamma. Ch55 bound all three subtypes of rRARs, preferentially rRAR beta/E. These results suggest that the intrinsic nature of the binding of each retinoid can be investigated by usage of the rRARs. However, rRARs show quantitatively different ligand-selectivity from that of hRARs: RA showed higher binding affinity toward rRARs than both Am80 and Ch55, but Ch55 binds all three subtypes of hRARs stronger than RA and Am80, which binds hRAR beta stronger than RA.

Base Sequence↗
PubMed1993

[Retinoid signalling pathways].

Retinoids, all-trans-retinoic acid (AT-RA) and its bioisters, exert diverse and profound effects on the growth and differentiation of normal and malignant cells, vertebrate development, and homeostasis. Since their nuclear receptors (RARs: alpha, beta and gamma) were cloned, extensive studies on retinoid signalling at molecular level have elucidated its elaborate mechanisms, by which the expression of a variety of retinoid responsive genes are regulated. Furthermore, discoveries of the second receptor system of retinoid (RXRs: alpha, beta and gamma) and their substantial ligand, 9-cis-retinoic acid (9C-RA), were recently reported. The heterodimer formation between RXR and RAR or other members of the steroid/thyroid hormone receptor superfamily gave us a new aspect of hormonal gene control including retinoids, thyroid hormone, vitamin D3 and others. These heterodimers were showed to bind specific response elements consisted of the direct repeat of consensus sequence (AGATTC) or its related sequences. Differential regulation of retinoid responsive gene by RARs or/and RXRs in vivo is an ongoing subject and the combinatory outcome of subtypes or isotypes of receptors, natural response elements, natural ligands (AT-RA, 9C-RA, or their metabolites) owing to pleiotropic effects of retinoids is being revealed. The anti-malignant effect of retinoids is another important theme. The report of prominent therapeutic effect of AT-RA against APL patients was sensational. In many APL patients, translocation between RAR alpha gene and an oncogenic gene, PML, can be detected, although the roles of their fusion products (RAR alpha-PML and PML-RAR alpha) in APL induction have not been understood. Furthermore, the cross-talk between RAR and AP-1 is thought to give an explanation for the suppressive effects of retinoids against tumor promoters (TPA and others). In those contexts, synthetic retinoids specific for each subtype of RAR or RXR, which will be useful reagents for biological studies and/or excellent therapeutic agents, are being developed. Some RAR subtype-selective compounds including antagonists have been already reported.

Animals↗
PubMed1992

Base-catalyzed isomerization of retinoic acid. Synthesis and differentiation-inducing activities of 14-alkylated all-trans-, 13-cis-, and 20,14-retro-retinoic acids.

Retinoic acid (1) is isomerized regioselectively by excess amounts of lithium diisopropylamide (LDA) to give 20,14-retro-retinoic acid (3). Alkylation of the intermediate dianion of retinoic acid gave 14-alkylated derivatives of 3. By isomerization of the alkylated retro isomers under basic conditions, several 14-alkyl-all-trans- and -13-cis-retinoic acids were synthesized. The retinoidal activities of these derivatives were examined, based on the ability to induce differentiation of human promyelocytic leukemia cell line HL-60. 20,14-retro-Retinoic acid (3) is 1/50 as active as retinoic acid (1). Although 14-methyl-20,14-retro-retinoic acid (4) is as active as 3, the introduction of a 14-methyl group into all-trans- and 13-cis-retinoic acid resulted in decreased activity. Introduction of bulkier alkyl groups at the C-14 position caused the disappearance of the activity.

Alkylation↗
PubMed1992

Effect of niceritrol on streptozocin-induced diabetic neuropathy in rats.

Niceritrol, a drug with peripheral tissue vasodilatory and serum lipid-lowering activity, was administered for 2 mo to rats with streptozocin-induced diabetes. Physiological and biochemical studies were subsequently conducted on rat nerve tissue. A markedly lower value of approximately 47% in sciatic nerve blood flow (SNBF) was detected in an untreated diabetic (DC) group than in a nondiabetic control group (CC). A significant delay in caudal motor nerve conduction velocity (MNCV) and significantly higher glucose, sorbitol, and fructose values were observed in the sciatic nerve and serum lipids. In contrast, a niceritrol-treated diabetic (DN) group had significantly higher SNBF, MNCV, and sciatic nerve myo-inositol values and lower serum triglyceride levels than group DC. No differences between these two groups were noted in glucose, sorbitol, and fructose levels in the sciatic nerve, or in cholesterol and glucose in serum. These findings suggest that niceritrol has a clear inhibitory effect on the development of delayed MNCV in the diabetic rat, which may be due to reduced nerve blood flow and/or decreased nerve myo-inositol levels.

Animals↗
PubMed1991

Effects of a Ca2+ entry blocker (nilvadipine) on acute focal cerebral ischemia in rats.

The effects of nilvadipine, a Ca2+ entry blocker, on focal cerebral ischemia were investigated in rats having unilateral middle cerebral artery occlusion. All rats had 24 h ischemia, and were divided into three groups (ten rats per group). Groups 1 and 2 received 1.0 and 3.2 mg/kg nilvadipine s.c. respectively, just after the occlusion. Control rats received an equal volume of the vehicle. Control animals had a % infarct volume of 28.2 +/- 11.4%, and a left/right hemispheric volume ratio of 112 +/- 12%. Group-1 and -2 rats had % infarct volumes of 25.5 +/- 11.6% and 13.9 +/- 9.2% (p less than 0.01) respectively, and left/right hemispheric volume ratios of 111 +/- 9% and 103 +/- 7% (p less than 0.05), respectively. Thus, the drug reduced the infarct size and the brain edema in a dose-dependent manner. The significant decrease in the infarct volume was observed in the periphery of the frontoparietal cortex. This study supports the hypothesis that nilvadipine may be a potential therapeutic agent for cerebral ischemia. Neuropathological findings suggest the possible therapeutic effects of the drug in the ischemic penumbra.

Acute Disease↗
PubMed1991

Rat middle cerebral artery occlusion using an intraluminal thread technique.

A modification of the previous methods of producing cerebral ischaemia in rats (Koizumi et al., Longa et al.), using an intraluminal thread technique, is described. The middle cerebral artery is occluded by introducing a simple 3-0 nylon thread (0.20-0.249 mm in diameter) through the internal carotid artery in the neck. It has been proven that with this method reproducible focal cerebral ischaemia can be achieved which resembles human stroke. Therefore this simple and relatively non-invasive model is suitable for the pathophysiological investigation of ischaemic stroke and the testing of potential therapies.

Animals↗
PubMed1991

In vitro retinal and erythrocyte polyol pathway regulation by hormones and an aldose reductase inhibitor.

The effects of a high-glucose medium, insulin, and an aldose reductase inhibitor (ONO-2235) on sorbitol accumulation were compared in the human erythrocyte and the rabbit retina, while the effects of epinephrine on in vitro sorbitol accumulation were investigated in the human and rabbit retina. In both erythrocytes and the retina, linear increments of sorbitol accumulation were observed in a dose-dependent manner with 5 to 50 mM glucose. These increments were markedly inhibited by 100 microM ONO-2235 but not by insulin (400 microU/ml). In the presence of 5 mM glucose, a dose-dependent increase of the sorbitol content of the rabbit retina was seen following epinephrine stimulation (0.4-4.0 microM and this was markedly reduced by 100 microM ONO-2235. Moreover, both 50 mM glucose and 4.0 microM epinephrine increased the sorbitol content of the retina from a diabetic patient, and the glucose-induced increment in sorbitol was significantly reduced by 100 microM ONO-2235. Our data suggested that aldose reductase inhibitors might be useful for the treatment of diabetic retinopathy, since the polyol pathway appears to be an important factor in its pathogenesis, and that catecholamines might have some role in the activation of the retinal polyol pathway.

Aged↗
PubMed1991

Chloroplast DNA topoisomerase I from cauliflower.

An ATP-independent DNA topoisomerase has been isolated from chloroplasts of cauliflower leaves (Brassica oleracea var. botrytis) through DEAE-cellulose, AF-blue Toyopearl, and hydroxyapatite column chromatography. The sedimentation coefficient and Stokes radius of this enzyme are 3.6S and 3.6 nm, respectively, and the molecular weight of native enzyme is estimated to be 54,000. This enzyme changes the linking number in steps of one. The enzyme activity is stimulated by MgCl2, and this enzyme shows optimum activity at 30 degrees C in the range of 3 mM MgCl2 + 100 mM KCl-10 mM MgCl2 + 50 mM KCl. The enzyme activity was reduced remarkably by N-ethylmaleimide, indicating that a free sulfhydryl group is important for the activity; heparin and ellipticine also reduced the activity. Both cauliflower chloroplast topoisomerase and spinach chloroplast topoisomerase can relax positive supercoils as well as negative supercoils. From these properties, cauliflower chloroplast topoisomerase can be classified as a eukaryotic type I DNA topoisomerase.

Chloroplasts↗