Biomedical subjects

H Fukasawa

Publications and source records attributed to H Fukasawa.

At least 55 records · Page 3Linked to original sources

PubMed1996

Protective effect of nilvadipine on focal cerebral ischemia in spontaneously hypertensive rats.

The protective effect of nilvadipine, a Ca2+ antagonist, on cerebral ischemia was investigated in spontaneously hypertensive rats. The 12-week-old animals were treated for 7 days with either nilvadipine or vehicle using osmotic pumps implanted subcutaneously. Group 1 animals (n = 10) received the vehicle, and Group 2 (n = 10) and 3 animals (n = 10) received 1 and 3 mg/kg/day nilvadipine, respectively. The left middle cerebral artery was occluded under halothane anesthesia on the 6th day of treatment, and neuropathological outcomes were quantified 24 hours later. The systolic blood pressure measured before occlusion decreased to 137 +/- 9 mmHg (Group 2) and 130 +/- 9 mmHg (Group 3), compared to 189 +/- 12 mmHg for Group 1 (p < 0.05). The percentage infarct volumes in Groups 1-3 were 39 +/- 3%, 37 +/- 2%, and 34 +/- 3%, respectively (p < 0.05, Groups 1 vs. 3). Therefore, nilvadipine decreased the infarct size dose-dependently. Nilvadipine has a protective effect against cerebral ischemia in rats with chronic hypertension. Neuropathological findings suggest that nilvadipine may act at the ischemic penumbra. Nilvadipine may have the additional benefit of reducing the consequences of a possible later stroke in patients with hypertension (one of the risk factors for stroke).

Animals↗

PubMed1996

Effects of beraprost sodium and insulin on the electroretinogram, nerve conduction, and nerve blood flow in rats with streptozotocin-induced diabetes.

The effect of a prostacyclin analog, beraprost sodium, on the electroretinogram, motor nerve conduction velocity, and nerve blood flow was determined in rats with streptozotocin-induced diabetes and was compared with the effect of insulin. Beraprost sodium (0.01 mg x kg-1 x day-1 for 8 weeks) significantly shortened the peak latency of the electroretinogram b-wave, increased tail nerve conduction velocity, and increased sciatic nerve blood flow in diabetic rats (P < 0.0003, 0.0001, and 0.0001 vs. untreated diabetic rats, respectively). This was accompanied by a significant increase in the 6-keto-prostaglandin F1alpha content of the thoracic aorta and a marked increase in the cAMP content of the sciatic nerve. Beraprost sodium had no effect on the sorbitol and fructose contents of the sciatic nerve and retina, but insulin (8-10 U/day) significantly reduced both parameters. These findings suggest that beraprost sodium may be useful for prevention of vascular and neural dysfunction in the retina and peripheral nerve.

6-Ketoprostaglandin F1 alpha↗

PubMed1995

Determination of the photoaffinity-labeled site on the ligand-binding domain of retinoic acid receptor alpha.

The ligand-binding domain of human retinoic acid receptor alpha (hRAR alpha) was photoaffinity-labeled with a fluorescent retinoid, ADAM-3, by the use of a recombinant fused protein constructed from a maltose-binding protein and the E/F-domain of hRAR alpha (MBP-RAR alpha/E), which was expressed in E. coli. The labeled site was identified as Arg-589 (this corresponds to amino acid residue 385 of hRAR alpha) or a residue in its vicinity.

Affinity Labels↗

PubMed1995

Correlation of differentiation-inducing activity of retinoids on human leukemia cell lines HL-60 and NB4.

Retinoids, including all-trans-retinoic acid, its isomers, and fifty synthetic retinoids (retinobenzoic acids), were tested for differentiation-inducing activity on human leukemia cell lines HL-60 and NB4. A good linear correlation, with an r value of 0.91, between the ED50 values for the differentiation-inducing activity towards HL-60 cells and that towards NB4 cells was found.

Cell Differentiation↗

PubMed1995

Lymphadenectomy in stage-III serous cystadenocarcinoma of the ovary.

OBJECTIVE: To elucidate the effects of lymphadenectomy on the prognosis for ovarian cancer. METHOD: A retrospective study of 69 patients with stage-III serous cystadenocarcinoma was performed. RESULTS: Among the 69 patients, 36 were not treated by lymphadenectomy. Both pelvic and para-aortic lymphadenectomies were performed on 13 patients at the initial operation and on 11 at the second operation. The group (n = 13) treated by both pelvic and para-aortic lymphadenectomies at the initial operation had a disease-free survival rate that was significantly higher than the non-lymphadenectomy group (n = 36) or the group (n = 5) treated by pelvic or para-aortic lymphadenectomy alone (P < 0.04). These 54 patients were subjected to multivariate analysis for lymphadenectomy at the initial operation, and a significant correlation was found between disease-free survival rate and both pelvic and para-aortic lymphadenectomies (P < 0.05). CONCLUSION: These results suggest that systematic lymphadenectomy can reduce the rate of recurrence.

Adult↗

PubMed1995

Effect of a potent new aldose reductase inhibitor, (5-(3-thienyltetrazol-1-yl)acetic acid (TAT), on diabetic neuropathy in rats.

(5-(3-Thienyl)tetrazol-1-yl)acetic acid (TAT), a novel potent aldose reductase inhibitor, was administered for 4 weeks to rats with streptozotocin-induced diabetes. Physiological and biochemical studies were subsequently conducted on rat nerve tissue and erythrocyte sorbitol content was estimated. Sciatic nerve blood flow (SNBF) was markedly lower (about 43.4%) in untreated diabetic (DC) rats than in non-diabetic controls (NC). A significant delay in caudal motor nerve conduction velocity (MNCV) and significantly higher glucose, sorbitol and fructose values were observed in the sciatic nerve, accompanied by a markedly higher sorbitol concentration in erythrocytes. In contrast, TAT-treated diabetic groups (DT-10, DT-40 and DT-200) had significantly higher SNBF, MNCV and sciatic nerve myo-inositol values and lower sciatic nerve sorbitol and fructose levels and erythrocyte sorbitol concentration than the DC group. There were good correlations between SNBF and MNCV (r = 0.672, P < 0.001) and between SNBF and erythrocyte sorbitol (r = 0.455, P < 0.003). These findings suggest that both vascular and metabolic factors play an important role in diabetic neuropathy and the effect of aldose reductase inhibitors on diabetic neuropathy may be mediated by at least these two factors.

Aldehyde Reductase↗

PubMed1995

An aldose reductase inhibitor, TAT, prevents electroretinographic abnormalities and ADP-induced hyperaggregability in streptozotocin-induced diabetic rats.

Rats with streptozotocin-induced diabetes were oral given TAT, a potent aldose reductase inhibitor, at a dose of 10 mg kg-1 day-1 or 40 mg kg-1 day-1 for 30 days. Prolongation of the peak latency of oscillatory potentials in the b-wave of the electroretinogram (ERG), which is associated with retinal Müller cell dysfunction, was significantly improved by treatment with TAT as compared with untreated diabetic rats [sigma(O1 + O2 + O3) was 106.8 +/- 1.8 ms in normal controls (NC), 118.2 +/- 1.1 ms in diabetic controls (DC) (P < 0.001 vs. NC), 110.8 +/- 1.5 ms with 10 mg kg-1 TAT (P < 0.001 vs. DC) and 111.4 +/- 1.6 ms with 40 mg kg-1 TAT (P < 0.01 vs. DC)]. The improvement in ERG abnormalities in diabetic rats was accompanied by partial reduction of elevated sorbitol levels in the retina and erythrocytes, and by correction of platelet hyperaggregability. The authors' findings suggest that a better understanding of the mechanism by which TAT acts may provide new insights into the pathogenesis of hyperglycaemic retinal dysfunction and contribute to establishing effective therapy for diabetic retinopathy.

Adenosine Diphosphate↗

PubMed1995

Synergists for retinoid in cellular differentiation of human promyelocytic leukemia cells HL-60.

4-[5H-2,3-(2,5-Dimethyl-2,5-hexano)-5-methyldibenzo[b, e]diazepin-11-yl]benzoic acid (4) enhanced the differentiation-inducing activity of retinoic acid (1) and of a synthetic retinoid Am80 (2) toward human promyelocytic leukemia cells HL-60, although 4 alone did not induce differentiation. The synergistic effect of 4 on the activities of retinoids was also seen in suppression of proliferation of HL-60 cells.

Cell Differentiation↗

PubMed1994

Retinobenzoic acids. 6. Retinoid antagonists with a heterocyclic ring.

Several candidate retinoid antagonists were designed on the basis of the ligand superfamily concept and synthesized. Retinoidal activities of these benzimidazole and benzodiazepine derivatives were examined by assay of differentiation-inducing activity on human promyelocytic leukemia cell line HL-60. The parent benzimidazole derivative, 4-(5,6,7,8-tetrahydro-5,5,8,8- tetramethylnaphth-[2,3-d]imidazol-2-yl)benzoic acid (7a), and related compounds with a small alkyl group instead of the hydrogen on the nitrogen (1N) atom of the imidazole ring exhibited retinoidal activity, and the potency strongly depended on the bulkiness of the substituent. The compounds having a phenyl or benzyl group on the nitrogen lacked differentiation-inducing activity on HL-60 cells and acted as antagonists to the potent retinoid 4-[(5,6,7,8-tetrahydro-5,5,8,8- tetramethyl-2-naphthalenyl)carbamoyl]benzoic acid (Am80). Among the compounds possessing a seven-membered heterocyclic ring as a linking group, 4-(5H-7,8,9,10-tetrahydro-5,7,7,10,10- pentamethylbenzo[e]- naphtho[2,3-b][1,4]diazepin-13-yl)benzoic acid (16) also exhibited the antagonistic activity. The binding abilities of these compounds to retinoic acid receptors alpha and beta were consistent with their potency for the inhibition of HL-60 cell differentiation induced by the retinoid Am80.

Benzimidazoles↗

PubMed1994

Therapeutic effects of nilvadipine on rat focal cerebral ischemia.

The present study was conducted to investigate the therapeutic effects of nilvadipine, a Ca2+ entry blocker, on rat focal cerebral ischemia. Under halothane anesthesia, a 3-0 nylon thread was introduced into the neck internal carotid artery to occlude the left middle cerebral artery. Either nilvadipine (3.2 mg/kg) or vehicle was administered subcutaneously 1, 2, 3, 4, 5 and 6 h following the occlusion (groups 1-6, respectively). Twenty-four hours after the occlusion, the percentage infarct volumes in nilvadipine-treated animals in groups 1-3 (21 +/- 11%, 24 +/- 11%, and 26 +/- 7%, respectively) were smaller than those in the respective control groups (36 +/- 5%, 35 +/- 3%, and 35 +/- 3%; P < 0.05). Compared with controls, the infarct size of the periphery of the fronto-parietal cortex decreased in nilvadipine-treated animals. The results indicate that nilvadipine decreases the size of infarction when administered up to 3 h after an ischemic insult. Thus, nilvadipine can be considered a potential therapeutic agent for acute focal cerebral ischemia, and may be clinically useful in stroke patients.

Animals↗

PubMed1994

The anterior choroidal artery syndrome. I. Microangiography of the anterior choroidal artery.

The distribution of the anterior choroidal artery (AChA) was analysed on coronal, sagittal and axial microangiograms of cadaver brains. On axial sections, the territory of the AChA was confined to an arcuate zone between the striatum anterolaterally and the thalamus posteromedially. On sagittal sections, fine vessels from the cisternal part of the AChA were seen to extend upwards and somewhat posteriorly into the region of the posterior limb of the internal capsule. On coronal sections, ascending branches of the AChA coursed laterally and then upwards to penetrate the globus pallidus and the inferior portion of the posterior limb of the internal capsule, apparently terminating at the lateral border of the thalamus. Determining the distribution of this artery on multiplanar sections was helpful for interpreting pathological changes, including infarcts, occurring in this region on multiplanar CT and/or MR images.

Cerebral Angiography↗

PubMed1994

Reversible middle cerebral artery occlusion in rats using an intraluminal thread technique.

We investigated the temporal profile for neuropathologic outcomes after cerebral ischemia using a rat model of reversible middle cerebral artery occlusion, where reperfusion can be introduced in nonanesthetized rats. Reperfusion was performed 1 hour to 5 hours after the occlusion. Control animals underwent permanent occlusion. The results indicate that the time window to reduce infarct volume is 2 hours, and that a > or = 3-hour duration of ischemia is sufficient to attain the maximal infarction observed after permanent ischemia. This suggests that any therapies that follow the therapeutic window will provide little benefit for transient cerebral ischemia and reperfusion injury.

Animals↗

PubMed1994

Pulsatile flow and simple flow control method during weaning period in centrifugal pump: toward more expanded usage in open heart surgery.

To expand the usage of the centrifugal pump (CP) in open heart surgery, we performed two studies. In the first, we evaluated pulsatile flow in the CP. In vitro pump performance of the Terumo Capiox pump (TCP) and the Sarns Delphin pump (SDP) and increase of free hemoglobin (mg/dl) after driving 6 h were investigated using bovine blood. A roller pump (RP) was used as a comparison. Equally effective pulsatile flow was obtained in both CPs. Hemolysis was less severe in TCP (120 mg/dl) than SDP (210 mg/dl) and RP (320 mg/dl). In the second study, we evaluated a simple flow control method. Flow rate was easily controlled with step-wise clamping of 3-pronged tubing (Triple-flow) without changing rotational speed, regardless of afterload. Fluctuation of flow was much less with this method than with the rotational speed change method. The use of pulsatile flow of TCP, with its minimum increase of hemolysis and the easier flow control method during the weaning process, may expand the usage of CP in open heart surgery.

Animals↗

PubMed1994

The margin of safety in the use of a straight path centrifugal blood pump.

A new centrifugal blood pump with a rotor that arranges 6 straight paths radially was developed for open heart surgery and temporary circulatory support. We describe comparative studies of the margin of safety in the practical use of the new pump. This pump was evaluated for temperature increase, cavitation, and pressure sensitivity. Two commercially available centrifugal pumps, the Biomedicus cone type and the Sarns 3M impeller type, were used as control pumps. The temperature increase in the new pump was four times slower than in the impeller pump when the outlet and the inlet of the pump was clamped. No sign of cavitation was observed when 0.1 ml air was introduced to the pump inlet under a negative pressure of 200 mm Hg in fresh bovine blood. As for pressure sensitivity of centrifugal pumps in practical applications, circuit resistance was a more essential factor than flow-pressure curves of the pump.

Animals↗

PubMed1994

Specific binding of 12-O-tetradecanoylphorbol-13-acetate to histone H1.

12-O-Tetradecanoylphorbol-13-acetate (TPA) binds specifically to histone H1 prepared from HeLa cells and to calf histone H1 with dissociation constants of 4.3 x 10(-7) and 9.3 x 10(-7) M, respectively. The TPA-binding to histone H1 was confirmed immunologically using a monoclonal antibody directed against an evolutionally conserved epitope of histone H1. This binding would influence DNA structure and the basal level of transcription, and may, in turn, account for the cell growth-regulatory activity of TPA.

Amino Acid Sequence↗

PubMed1994

Enhancement of human papillomavirus type 18 gene expression in HeLa cells by 12-O-tetradecanoylphorbol-13-acetate, 3 beta,5 alpha-dihydroxycholestan-6-one, and cholesterol.

Human papillomavirus type 18 (HPV18) is involved in the genesis of cervical cancer through expression of its viral oncoprotein in infected cells. A tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), was found to increase the level of HPV18 transcripts in an HPV18-harboring cervical cancer cell line, HeLa. A similar increase in HPV18 expression was also observed on treatment of the cells with an oxygenated cholesterol, 3 beta,5 alpha-dihydroxycholestan-6-one (yakkasterone). The effects on HPV18 expression elicited by TPA and yakkasterone were repressed by a protein kinase inhibitor, staurosporine. Treatment of the cells with cholesterol under serum-free conditions also resulted in an apparent increase of HPV18 expression.

Alkaloids↗

PubMed1994

Synthesis of oxygenated cholesterols as structural mimics of phorbol ester-type tumor promoters.

We designed several oxygenated steroids in which functional groups including a hydrophobic group are arranged analogously to those of phorbol ester (12-O-tetradecanoylphorbol-13-acetate, TPA), with the aim of finding compounds with TPA-like activity, but having a different skeleton and a rigid conformation. The designed steroids, 1 beta,5 alpha-dihydroxy-3 beta-hydroxymethylcholestan-6-one (4), 3 beta,5 alpha-dihydroxycholestan-6-one (5), 3 beta-hydroxymethylcholestan-5 alpha-ol-6-one (6) and 1 beta,3 beta,5 alpha-trihydroxycholestan-6-one (7), were synthesized. A related oxygenated steroid isolated from soft coral, cholestane-1 beta,3 beta-5 alpha,6 beta-tetrol (8), was also synthesized. Among these analogs, compound 7 showed weak TPA-like activities in three biological tests: inhibition to protein kinase C and to cytosolic-nuclear tumor promoter-binding protein (CN-TPBP), and induction of differentiation of human promyelocytic leukemia cells (HL-60) to monocyte-like cells. On the other hand, compound 5 was found to be a specific ligand for CN-TPBP, but lacked the other TPA-like activities.

Animals↗

PubMed1994

Extent and location of cerebral infarcts on multiplanar MR images: correlation with distribution of perforating arteries on cerebral angiograms and on cadaveric microangiograms.

The basal gray matter in the cerebrum is supplied by different anatomical groups of perforating arteries, including striate, thalamic, and choroidal arteries. In this pictorial essay we illustrate multiplanar MR imaging of infarctions in those regions and correlate their appearances with cerebral angiographic findings of the same patients when available. We also correlate the extent and location of infarctions on multiplanar MR images with the anatomical distributions of perforating arteries seen on microangiograms of unrelated cadavers. Information conveyed from this correlation will increase understanding of patterns of basal cerebral infarction shown on cross-sectional imaging.

Aged↗