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Biomedical subjects

F Okada

Publications and source records attributed to F Okada.

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

Chronic desipramine treatment influences D1 stimulation and D2 inhibition (dual control) of adenylate cyclase by dopamine in rat striatum.

The response of adenylate cyclase to GTP and to dopamine (DA) was investigated in striatal membranes from desipramine (DMI)- or saline-treated rats. DMI (15 mg/kg) or saline was injected i.p. once a day for 3 weeks. In saline-treated control membranes, GTP exerted a biphasic effect on basal and DA-stimulated enzyme activity; peak levels of stimulation by DA plus GTP were observed at 1 microM GTP. On the other hand, peak levels moved to the right in the GTP dose response curve in DMI-treated membranes. Therefore, D2 inhibition might be attenuated, while the D2 specific agonist, PPHT, was not observed to cause inhibition of adenylate cyclase. Furthermore, D1 stimulation of adenylate cyclase via D1 specific agonist SKF was attenuated in DMI-treated membranes. It seems, therefore, that chronic treatment of rat striatum with DMI exerts a dual influence, that is, a lessening of both D1 stimulation and D2 inhibition of adenylate cyclase, and alters specifically the overall process of the adenylate cyclase system.

Adenylyl Cyclase Inhibitors↗
PubMed1994

Differentiation between parasystole and extrasystoles. Influence of vagal stimulation on parasystolic impulse formation.

Recently, it has been shown that when a sinus impulse falls late in the parasystolic cycle, it usually hastens the next ectopic discharge. Thus, in many cases, the classic criteria for the diagnosis of parasystole (ie, varying coupling intervals and constant shortest interectopic intervals) cannot be used. To differentiate between parasystole and extrasystoles in such cases, the influence of vagal stimulation on parasystolic impulse formation was investigated in seven cases of "true" parasystole in which one or more "pure" ectopic cycles without any intervening nonectopic QRS complexes were found spontaneously. In all cases pure ectopic cycles were found during sinus arrest caused by vagal stimulation; namely, none of the cases showed extreme prolongation of the parasystolic cycle. These results strongly suggest that instead of the classic criteria, vagal stimulation causing temporary sinus arrest is the optimal method for differentiation between parasystole and extrasystoles in cases without spontaneous pure ectopic cycles.

Adult↗
PubMed1994

Enhancement of in vitro prostaglandin E2 production by mouse fibrosarcoma cells after co-culture with various anti-tumour effector cells.

We have previously reported that an increase in the production of immunosuppressive prostaglandin E2 by a QR tumour (QR-32) is accompanied by progressive growth of the tumour in syngeneic C57BL/6 mice. In order to determine what kinds of cell and factor(s) enable QR-32 cells to promote PGE2 production, we investigated the amounts of PGE2 in the supernatant of QR-32 cells by co-culturing them with various anti-tumour effector cells. Significantly high levels of PGE2 production were observed when the QR-32 cells were co-cultured with lymphokine-activated killer (LAK) cells, natural killer (NK) cells, polymorphonuclear (PMN) leucocytes and streptococcal preparation (OK432)-activated or resident peritoneal macrophages (activated and resident macrophages). On the other hand, PGE2 production was not increased when QR-32 cells were co-cultured with cytotoxic T lymphocytes (CTLs) specific to QR-32 cells. The high levels of PGE2 production were partially or totally inhibited by the presence of radical scavengers such as superoxide dismutase (SOD), catalase and mannitol, although the cytotoxicity of LAK cells was not. We also exposed QR-32 cells to human recombinant cytokines and the growth factors which are produced when anti-tumour effector cells come in contact with tumour cells. Significant PGE2 production by QR-32 cells was observed when the cells were treated with interferon alpha (IFN-alpha), tumour necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta) (all P < 0.001). These results suggest that oxygen radicals produced by anti-tumour effector cells and inflammatory cytokines provoke QR-32 cells to produce large amounts of immunosuppressive PGE2.

Animals↗
PubMed1994

Antiemetic effects of serotonergic 5-HT1A-receptor agonists in Suncus murinus.

The antiemetic effects of six serotonergic 5-HT1A-receptor agonists, 8-hydroxy-2-(di-n-propylamino)tetrarin (8-OH-DPAT), 4-(4-[4-(2-pyrimidinyl)piperazin-1-yl]butyl)-2,3,4,5- tetrahydro-1,4-benzoxazepine-3,5-dione (SUN8399), buspirone, gepirone, ipsapirone and tandospirone, against motion sickness were investigated in Suncus murinus. Subcutaneous injection of all six agonists completely and dose-dependently suppressed motion-induced emesis. Pretreatment with 8-OH-DPAT or SUN8399 dose-dependently inhibited emesis elicited by nicotine (4.0 mg/kg, s.c.), veratrine (0.7 mg/kg, s.c.), cisplatin (20 mg/kg, i.p.) and copper sulfate (40 mg/kg, p.o.). These results suggest that serotonergic 5-HT1A-receptor agonists are effective as anti-motion sickness drugs, and these drugs may block a common mechanism(s) for the emetic reflex of the suncus because the antiemetic effects of the 5-HT1A-receptor agonists were exerted irrespective of the stimulus.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1994

Effects of a daily feeding-restriction on the reproductive and development toxicity parameters in female rats.

On the assumption of that the oral administration of an acid-unstable test compound into the empty stomach could enhance the systemic exposure to the test compound, the non-pregnant and pregnant rats had free access to the diet only for five hours per day. Female rats under the restricted feeding for a period of 21 days took diet at two thirds of the daily food-intake by the control animals, and lost their weight more than 10%. The vaginal smear test in these animals revealed a prolonged estrous cycle and diestrous period over four days. On the other hand, the restricted feeding from Day 0 to Day 17 of gestation suppressed the weight gain of pregnant animals but did not cause any significant influence upon the litter data, incidence of external anomalies or fetal skeletal development. The restricted feeding from Day 0 of gestation to Day 7 of lactation seriously disturbed the nursing behavior and the growth of offspring. These results suggested that the dosing method under the above-mentioned restricted feeding might be applicable to the teratology study but could not be applied to the fertility study nor to the peri- and post-natal study.

Abnormalities, Drug-Induced↗
PubMed1994

[Transcatheter embolization of aorto-pulmonary collateral arteries in cyanotic congenital heart disease].

Transcatheter embolization (TE) using steel coils was performed on three patients with aorto-pulmonary collateral arteries (APCAs). Case #1: In a 13-year-old boy who had undergone corrective surgery for pulmonary atresia with ventricular septal defect (PA with VSD), one APCA was embolized by the TE technique. This resulted in a remarkable improvement in postoperative pulmonary congestion. Case #2: A 13-year-old boy who had previously undergone procedures to correct tetralogy of Fallot (TOF), underwent TE for two APCAs prior to subsequent surgery before for pulmonary stenosis. The procedure abandoned one APCA because of the long narrow origin of the vessel. For the other APCA, TE was unsuccessfully performed due to the displacement of a coil into the peripheral pulmonary artery. Case #3: An 8-year-old girl with PA with VSD underwent TE for three APCAs before corrective surgery. One APCA arising from the abdominal aorta was occluded successfully. The other two were considered too small at the orifice for TE, and were ligated surgically before corrective surgery. TE is a safe and effective method for suitable cases of APCAs. However, caution should be exercised to prevent complications. The selection of appropriate coils and catheters is also important.

Adolescent↗
PubMed1993

Gender- and handedness-related differences of forebrain oxygenation and hemodynamics.

To elucidate gender- and handedness-related differences between the hemispheres of the brain in their metabolisms and hemodynamics, simultaneous monitoring by near-infrared (NIR) spectrophotometry of hemoglobin (Hb) in both hemispheres of the forebrain during the mirror drawing task (MDT) was performed. Bilaterally simultaneous increases of oxygenated Hb and decreases of deoxygenated Hb in forebrain occurred symmetrically in all cases of volunteer subjects except for two. There were gender- and handedness-related differences of hemodynamics between the hemispheres of the brain; NIR results showed that a large majority of women used both sides of the brain when concentrating on carrying out the MDT, whilst most men, especially left-handers, reacted mainly using the hemisphere which was 'dominant' according to handedness.

Adult↗
PubMed1993

The mechanism for the activation of latent TGF-beta during co-culture of endothelial cells and smooth muscle cells: cell-type specific targeting of latent TGF-beta to smooth muscle cells.

Transforming growth factor-beta (TGF-beta) is secreted in a latent form and activated during co-culture of endothelial cells and smooth muscle cells. Plasmin located on the surface of endothelial cells is required for the activation of latent TGF-beta (LTGF-beta) during co-culture, and the targeting of LTGF-beta to the cellular surface is requisite for its activation. In the present study, the cellular targeting of LTGF-beta was examined. We detected the specific binding of 125I-large LTGF-beta 1 isolated from human platelets to smooth muscle cells but not to endothelial cells. A mAb against the latency-associated peptide (LAP) of large LTGF-beta 1 complex, which blocked the binding of 125I-large LTGF-beta 1 to smooth muscle cells, inhibited the activation of LTGF-beta during co-culture. The binding of 125I-large LTGF-beta 1 could not be competed either by mannose-6-phosphate (300 microM) or by the synthetic peptide Arg-Gly-Asp-Ser (300 micrograms/ml). These results indicate that the targeting of LTGF-beta to smooth muscle cells is required for the activation of LTGF-beta during co-culture of endothelial cells and smooth muscle cells. The targeting of LTGF-beta to smooth muscle cells is mediated by LAP, and the domain of LAP responsible for the targeting to smooth muscle cells may not be related to mannose-6-phosphate or an Arg-Gly-Asp sequence, both of which have been previously proposed as candidates for the cellular binding domains within LAP.

Amino Acid Sequence↗
PubMed1993

Progression of a weakly tumorigenic mouse fibrosarcoma at the site of early phase of inflammation caused by plastic plates.

To elucidate tumor progression-enhancing factor(s), we examined the effects of host inflammation and host immunological status on in vivo tumor progression. One x 10(4) cells of QR clones (QR-32, -20 and -18), regressor tumor clones of 3-methylcholanthrene-induced fibrosarcoma, were unable to grow when injected s.c. into C57BL/6 mice in cell suspension form. However, QR clones grew and were lethal when s.c. implanted, attached to plastic plates. Furthermore, the tumor lines (QRpP) obtained from the tumors which had arisen from the plate-attached QR-32 clone cells no longer required plastic plates for their growth in normal mice, and had acquired stable malignant phenotypes. Although QR-32 cells became lethal when injected at the site of plastic plate implantation 1, 5 and 10 days before tumor injection, few tumors developed when plastic plates had been implanted 20 or 30 days before tumor injection. We established culture clones from the tumors arising in normal mice and mice immunosuppressed by irradiation. Clones derived from the tumors which had arisen in normal mice after implantation with plastic plates were lethal when re-implanted in normal mice (71%). On the other hand, clones derived from the tumors that arose in irradiated mice with or without plastic plates were lethal in only a few normal mice, when re-implanted (20 and 8%, respectively). These results indicate that QR clone cell progression is enhanced by the early phase of inflammation at the site of plastic plate implantation and that the progression-enhancing activity of co-implantation with a plastic plate is inhibited by previous whole-body irradiation of hosts.

Animals↗
PubMed1993

[Enhanced malignancy of tumor cells by the interaction with host cells reactive to foreign body].

We examined factors promoting malignant progression using a weakly malignant variant cell line, ER-1, derived from c-SST-2, a rat mammary carcinoma. ER-1 cells were converted to a highly malignant phenotype (highly tumorigenic, metastatic, invasive in vitro) by the in vitro/in vivo interaction with host cells reactive to foreign body. Epidermal growth factor (EGF) and transforming growth factor-beta (TGF-beta) produced by host reactive cells, transiently enhanced the tumorigenicity and in vitro invasiveness of ER-1 cells into an endothelial cell monolayer. The host reactive cells also produced oxygen radicals and induced mutations in ER-1 cells. It is speculated that mutations induced by host reactive cells cause cellular diversification, including the emergence of highly malignant variant cells whose growth is selectively promoted by growth factors such as EGF and TGF-beta.

Animals↗