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Biomedical subjects

F Okada

Publications and source records attributed to F Okada.

At least 55 records · Page 3Linked to original sources
PubMed1995

The role of cyclic AMP in the lipopolysaccharide-induced suppression of thymidine kinase activity in macrophage.

We observed that lipopolysaccharide (LPS, 1 micrograms/ml) can suppress [3H]thymidine incorporation into acid-insoluble fraction in a mouse macrophage cell line J774 (over 70% at 6 h) without affecting the uptake of [3H]thymidine or DNA polymerase activity. Paralleling this suppression, a decrease in the thymidine kinase (TK) activity, but not of thymidine monophosphate (TMP) kinase and thymidine diphosphate (TDP) kinase, was observed. LPS dose-dependently increased intracellular cAMP levels to about 3.5-times basal at 6 h, proportionally to the decrease of the TK activity. Elevation of intracellular cAMP by several reagents also decreased TK activity. Apparently LPS treatment elevates cAMP concentration by decreasing the low Km cAMP phosphodiesterase activity (58% at 6 h). The time course of cAMP-dependent protein kinase (PK-A) activity during the first 6 h after LPS treatment correlated with that of cAMP concentration. Treatment with a PK-A inhibitor restored about 63% of LPS-induced reduction of TK activity at 6 h. At longer times, however, there was a discrepancy between the change of cAMP concentration or PK-A activity and the reduction of TK activity. Therefore, protein kinase activation caused by the accumulation of intracellular cAMP probably triggers some mechanism responsible for the reduction of the TK activity.

Cells, Cultured↗
PubMed1995

Bradycardia- and tachycardia-dependent termination of ventricular bigeminy: mechanism of ventricular extrasystoles with fixed coupling.

Fourteen men with intermittent ventricular bigeminy were selected for this study because coupling intervals of the extrasystoles were considerably long and usually fixed, and bradycardia-dependent (10 cases) and/or tachycardia-dependent (12 cases) termination of bigeminy occurred. In all cases, when the heart rate ranged between two certain values, ventricular bigeminy with fixed-coupled extrasystoles was sustained. In all cases showing bradycardia-dependent termination, bigeminy was suddenly terminated with no changes in coupling of the preceding extrasystoles when the heart rate was decreased below a certain lower value. In all cases showing tachycardia-dependent termination except one, when the heart rate increased beyond a certain higher value, coupling intervals gradually lengthened until bigeminy was terminated. These findings strongly suggest the possibility that, in a considerably large number of clinical cases, ventricular extrasystoles with fixed coupling are caused by longitudinal dissociation of conduction in the reentrant pathway of extrasystoles.

Adult↗
PubMed1995

Region-dependent asymmetrical or symmetrical variations in the oxygenation and hemodynamics of the brain due to different mental stimuli.

The present paper demonstrates region-dependent variations in the oxygenation and hemodynamics of the brain hemispheres due to three different types of mental stimulation. The variations were observed with a four-channel optical imaging system using tissue-transparent near-infrared light and described changes from baseline of both the hemoglobin oxygenation state and blood volume during three kinds of psychological or mental tasks. During the mirror drawing task, a lateralized hemisphere response (the dominant hemisphere response pattern) was observed in 57% of 14 right handed volunteers in the frontal region (Brodmann's area 10), while in the temporal region (area 38), 80% showed the bilateral response pattern. A large majority of the subjects showed the bilateral response pattern in the frontal and temporal regions while calculating. A smaller majority showed this while looking at anatomical charts, though 30% did not show any response at all in the temporal region. This showed that there were region-dependent asymmetrical or symmetrical variations of the oxygen delivery-oxygen utilization relationship due to different types of mental stimuli.

Adult↗
PubMed1995

A possible role of 92 kDa type IV collagenase in the extramedullary tumor formation in leukemia.

Production of metalloproteinases such as collagenases has been reported to be involved in the metastasis of cancer cells. Granulocytic sarcoma in extramedullary sites can be formed by similar steps to other cancers. In this study, we have examined the secretion of type IV collagenases and a tissue inhibitor of metalloproteinase-1 (TIMP-1) in several human leukemia cell lines, including a granulocytic sarcoma-derived cell line established from a patient with granulocytic sarcomas in dermal tissues. We have also examined the invasive capacity of these leukemia cell lines into reconstituted basement membrane, Matrigel, which was used for in vitro invasion assay. Among the human leukemia cell lines used in this study, only the granulocytic sarcoma cell line was found to secrete type IV collagenase constitutively. Other myeloid leukemia cell lines such as HL-60 and U-937 produced type IV collagenase only after treatment with 12-O-tetradecanoylphorbol-13-acetate. All the cell lines secreted similar amounts of the tissue inhibitor of metalloproteinases. In vitro invasion assay revealed that the granulocytic sarcoma cell line showed higher invasive capacity than the other cell lines. These results suggest that the secretion of 92 kDa type IV collagenase plays a role in the leukemia cells' invasion of extramedullary tissues.

Collagenases↗
PubMed1995

Blockade of motion- and cisplatin-induced emesis by a 5-HT2 receptor agonist in Suncus murinus.

1. The effects of (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOl), a 5-hydroxytryptamine 5-HT2A/5-HT2C receptor agonist, on motion- and cisplatin-induced emesis were studied in Suncus murinus. Subcutaneous injection of DOl, 30 min prior to the emetic stimuli, dose-dependently blocked the emesis induced by motion sickness and cisplatin (20 mg kg-1, i.p.) with estimated ID50 values of 640 and 780 micrograms kg-1, respectively. 2. alpha-Methyl-5-hydroxytryptamine (alpha-Me-5-HT), a peripheral 5-HT2A/5-HT2C receptor agonist, had no effect on motion- and cisplatin-induced emesis. 3. The antiemetic effects of DOl on motion- and cisplatin-induced emesis were attenuated by preadministration of ketanserin, a selective 5-HT2A receptor antagonist. 4. The present results suggest an inhibitory role for central 5-HT2 receptors in the emetic reflex mechanism and that a 5-HT2 receptor agonist may be a useful tool to investigate the involvement of 5-HT receptors in the emetic reflex.

Amphetamines↗
PubMed1995

Effects of repeated doses of compound E for 4 and 9 weeks on the male reproductive organs.

Results of two toxicity studies of Compound E, which is an anticancer drug, on male reproductive organs and fertility by oral repeated dosing at dose levels of 12.5, 25 and 50 mg/kg/day for 4 and 9 weeks in rats were compared. After repeated dosing, the male fertility was studied by mating with untreated female animals. At the dose of 50 mg/kg/day in the 4-week study, Compound E significantly decreased testes weight and number of epididymal sperm, caused histopathological changes in the testis and epididymis characterized by decreased germ cells, but did not affect fertility. The dose of 25 mg/kg/day in the 9-week study caused reduction in epididymal weight and number of epididymal sperm and histopathological changes in the testis. The dose of 50 mg/kg/day in the 9-week study was lethal and caused more prominent toxic effects in the reproductive organs and loss of fertility. The present studies suggest that the order of sensitivity of parameters on male reproductive organs is as follows; histopathological examination = organ weight > number of sperm in epididymis > pregnancy index> copulation index. Further, 4-weeks repeated dosing is of sufficient duration to predict adverse effects of test compounds.

Animals↗
PubMed1995

Effect of lipopolysaccharide on thymidine salvage as related to macrophage activation.

Lipopolysaccharide (LPS), known as one of the potent activators of macrophages, has inhibitory effects on the proliferation of normal macrophages and macrophage-like cell lines. We report here that LPS dose- and time-dependently suppressed the tritiated thymidine ([3H]TdR) incorporation into the acid-insoluble fraction with a significant inverse correlation to the tumour necrosis factor-alpha (TNF) production in the J774.1 macrophage cell line. Among the three tested enzymes involved in DNA synthesis, only thymidine kinase (TK) activity decreased progressively in parallel with the decline in [3H]TdR incorporation, reaching 97% inhibition within 12 hr of LPS treatment, while changes in the activities of other two enzymes, DNA polymerase alpha and thymidylate synthase (TS), were less significant. On the other hand, LPS inhibited the cell proliferation only incompletely, as judged by 62% inhibition of cell growth at 36 hr. Even in the experiments done in a TdR-free medium, cell growth was inhibited by LPS to the same extent, suggesting that TK was not directly involved in the proliferation of J774 cells. LPS also inhibited the conversion of TdR to thymidine monophosphate (TMP) in murine peritoneal exudate macrophages (PEM). Thus LPS-induced suppression of TdR salvage related to TNF production is common in both normal and neoplastic macrophages, and therefore may be of potential importance in the process of macrophage activation.

Animals↗
PubMed1994

Reduced concentrations of the alpha-subunit of GTP-binding protein Go in schizophrenic brain.

Concentrations of the alpha-subunits of GTP-binding protein, Go (Go alpha) and of Gi2 (Gi2 alpha) in 6 areas (the hippocampus, parahippocampus, putamen, caudate head, orbital frontal cortex, and lateral temporal cortex) of control and schizophrenic postmortem brains were investigated using the highly sensitive enzyme immunoassay method. There was a significant decrease in Go alpha in the hippocampus and caudate head of the right hemisphere in schizophrenic patients compared to controls; the ANOVA (a general linear model; SAS Type II) demonstrated a significant diagnosis x side interaction only in the hippocampus. In other areas of the brain, analysis by grouping under diagnosis, side, age, gender, and postmortem delay showed no significant deviations in Go alpha between controls and schizophrenics. The concentrations of Gi2 alpha did not differ significantly in any area. These findings contrasted with the results yielded by ADP-ribosylation, which showed decreased pertussis toxin ADP-ribosylated amounts in the hippocampus and putamen of the contralateral (left) hemisphere. Some abnormal receptor-Go or Gi 1 signalling in hippocampus, putamen or caudate head may be involved in the pathogenesis of schizophrenia.

Aged↗
PubMed1994

Acceleration of desipramine-induced changes on the dopamine receptor-coupled adenylate cyclase system by pertussis toxin.

The response of adenylate cyclase to GTP and to dopamine (DA) was investigated in striatal membranes from desipramine (DMI)-treated rats (10 mg/kg, b.i.d., for 5 days). GPT exerted the same biphasic effect on basal and DA-stimulated enzyme activity in membranes from DMI-treated rats as on saline-treated rats. Rats were injected intraventricularly once with islet activating protein (IAP), pertussis toxin, and given extended treatment with DMI in order to study the effects on the inhibitory GTP-binding protein (Gi). Gi loses its function as a signal transducer on being ADP-ribosylated selectively by the IAP. D2 inhibition of adenylate cyclase by DA was attenuated by the IAP treatment in both DMI-and saline-treated rats; peak levels of DA plus GTP stimulation shifted from 1 microM to 100 microM GTP. D1 stimulation of adenylate cyclase by DA was also attenuated by the IAP in the DMI-treated rats. Since long-term treatment with DMI (15 mg/kg, once a day, for 3 weeks) resulted in suppression of D1 stimulation similar to that seen in the present findings, uncoupling between D2 receptors and Gi due to IAP treatment might accelerate DMI-induced adaptive changes of dual control of adenylate cyclase system by DA.

Adenosine Diphosphate Ribose↗
PubMed1994

Impaired interhemispheric integration in brain oxygenation and hemodynamics in schizophrenia.

We examined 38 patients with chronic schizophrenia to find and qualify disturbances in interhemispheric integration in brain oxygen metabolism and hemodynamics during a psychological task. A group of thirty-eight age- and sex-matched healthy volunteers were monitored as controls. Multi channel near-infrared (NIR) spectrophotometry was used to observed real-time alterations in cerebral oxygenation in areas of both hemispheres of the forebrain adjacent to the forehead during the mirror drawing task (MDT). In response to MDT normal volunteers showed distinct and well-integrated patterns of changes in oxygenated hemoglobin Hb, deoxygenated Hb, and blood volume total Hb. On the other hand, half the schizophrenics showed dysregulated patterns between hemispheres which never appeared in normal volunteers. Certain schizophrenic symptoms may be related to defective interhemispheric integration.

Adult↗