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Biomedical subjects

S Takada

Publications and source records attributed to S Takada.

At least 253 records · Page 14Linked to original sources

Oncogenic potential of hepatitis B virus.

The function of the X gene was clarified by examination of the transient production of hepatitis B virus (HBV) particles by transfected recombinant HBV DNA (pHBV-3 DNA) and its frameshift mutant (delta X) of the X open reading frame into hepatocellular carcinoma HuH-7 and HepG2 cells. No reduction of viral mRNAs was observed in the HuH-7 cells by the delta X mutant, whereas mRNAs underwent marked reduction in HepG2 cells. No reduction in core particle production was observed in HuH-7 cells, but in HepG2 cells reduction was considerable. To clarify the significance of the delta X mutation in the trans-acting function of the X gene in hepatoma cells, the chloramphenicol acetyl/transferase (CAT) assay was conducted. Transfection of plasmid pHBV-3 into HepG2 cells increased CAT activity of pSV2-CAT, while the delta X mutation clearly showed no stimulation of activity. On the other hand, in the HuH-7 cells, pHBV-3 exhibited no such stimulation. The trans-acting function of the X gene product in two different hepatoma cells was clearly shown to differ. Furthermore, transfection of X gene expression plasmid pKSV-HBx into mouse NIH3T3 cells increased the CAT activity of pSV2-CAT. Trans-activation was still detectable even following deletion of enhancer sequences in the pSV2CAT. The oncogenic potential of HBV is discussed with special attention to the X gene product, which may be able to activate a cellular transcription factor at the viral and cellular promotor sequences in the cells.

Animals↗

[Emergency operation in impending rupture of aortic arch dissecting aneurysm--a case report of dissecting aortic aneurysm with adhesion to the lung after lobectomy].

Successful surgical treatment of impending rupture of a aortic arch dissecting aneurysm in a 59-year-old man was reported. The aneurysm was tightly adhered to the lung, because he had a previous history of lobectomy. In this case, the permanent aortic bypass with permanent aortic clamp as a means of exclusion procedure of the aortic aneurysm was effective. The postoperative course was uneventful. In the emergency operation for aortic arch aneurysm, operative procedure should be selected by operative findings and risk.

Aortic Dissection↗

[The effects of ketanserin on vascular eicosanoid system in spontaneously hypertensive rats and their implications].

We designed experiments to reveal the effects of a S2 serotonergic receptor antagonist, ketanserin, on the vascular eicosanoid system and the relevance to medial hyperplasia in spontaneously hypertensive rats (SHR). 2-week ketanserin treatment (5 mg/kg/day) significantly decreased systolic blood pressure by 7% when compared to untreated SHR. The blood pressure reduction was associated with a significant decrease in vascular thromboxane A2 (TXA2) generation and sustained prostacyclin (PGI2) production, thereby shifting PGI2/TXA2 ratio toward vasodilatation. In contrast, the trichlormethiazide treatment, which achieved blood pressure reduction to almost the same extent, significantly decreased PGI2/TXA2 ratio. Vasodilator eicosanoids, e. g. PGI2, PGE2 and PGD2, dose-dependently decreased (3H)-thymidine uptake by vascular smooth muscle cells in culture whereas vasoconstrictor TXA2 enhanced (3H) thymidine uptake in a dose dependent manner. Indeed 2 x 10(-5) M ketanserin significantly decreased (3H) thymidine uptake by vascular smooth muscle cells by 48% although the same dose of methysergide, nonspecific serotonin inhibitor, did not affect the uptake by vascular smooth muscle cells. These results clearly indicate that the blood pressure reduction in ketanserin treatment is uniquely associated with a decrease in vascular thromboxane generation, and that it is possibly beneficial to protect vascular wall against medial hyperplasia of vascular smooth muscle cells, an integral component of arterial sclerotic changes in hypertension.

Animals↗

[Analysis of postoperative thoracic empyema].

We experienced 15 cases of pyothorax after thoracotomy. Six were pyothorax without bronchial fistula and 9 were with fistula. All of former were cured by the closed drainage and/or open window thoracostomy. Two of pyothorax with fistula, who were treated with the tube drainage, died of respiratory insufficiency. Five cases who underwent the open window thoracostomy survived well. Omentopexy was performed in 2 of pyothorax with fistula and results were excellent.

Adult↗

Probability that the commitment of murine erythroleukemia cell differentiation is determined by the c-myc level.

During the commitment of mouse erythroleukemia cell differentiation, c-myc mRNA levels change dramatically. To examine the involvement of c-myc in the commitment of these cells, we have introduced the rat c-myc gene driven by inducible, heterologous (human metallothionein IIA) gene promoter into murine erythroleukemia cells and we have examined the ability of the transformed cells to undergo commitment to terminal differentiation. The induction of the exogenous c-myc gene expression inhibited the commitment of these cells. Time-dependent inhibition of the commitment was observed with the addition of zinc at an appropriate time after the induction with dimethyl sulfoxide. The result clearly indicated that late decline, not early decline, is required for the commitment. By examining the transformants expressing the exogenous c-myc mRNA at different levels, and the induction of the exogenous c-myc mRNA by varying the concentration of zinc, we demonstrated that the commitment may be determined by a stoichiometric amount of c-myc in the defined period. The data also suggest that the probability value for the commitment process occurring in a stochastic manner is well-correlated with the amount of c-myc mRNA.

Animals↗

CD4 molecules are associated with the antigen receptor complex on activated but not resting T cells.

To explore the relationship between CD4 and CD3/Ti on the T cell surface, we have studied a panel of Ag-specific Th cell lines and clones, as well as resting and mitogen-activated CD4+ cells. Our results show that exposure of Th cells to their specific antigenic stimuli, but not to irrelevant stimuli, induced the rapid disappearance of approximately 20 to 35% of CD3 and CD4 molecules. The modulation of these molecules was detected in less than 1 h, became maximal at 12 h, and recovered thereafter in parallel. Treatment of Th cells with anti-CD4 antibody prevented Ag-induced modulation of CD3, and treatment with anti-CD3 blocked modulation of CD4. In the absence of Ag, treatment of these cells with an antibody (WT-31) directed at a conformational determinant within CD3/Ti or with the combination of anti-CD3 antibody and goat anti-mouse Ig, also resulted in significant modulation of CD4. Similar treatment of PHA-activated CD4+ T cells with anti-CD3/Ti antibodies also induced CD4 modulation; however, the same antibodies failed to affect CD4 expression on fresh resting T cells. These results indicate that on activated, but not resting T cells, CD4 molecules can be physically associated with CD3/Ti. We postulate that this association is essential for efficient Th cell activation, and further that the ability of anti-CD4 antibodies to inhibit helper functions is due to their prevention of CD4-CD3/Ti interaction on the T cell surface.

Antigen-Antibody Reactions↗

B cell hyperactivity and its relation to distinct clinical features and the degree of disease activity in patients with systemic lupus erythematosus.

Peripheral blood B cells that were actively proliferating, those actively secreting immunoglobulin, and those expressing an early activation marker, Ba antigens, on the surfaces were quantitated in 25 patients with systemic lupus erythematosus (SLE). B cell hyperactivity was found in almost all of the SLE patients, as demonstrated by any one of these measures of B cell activity. Moreover, we observed a strong positive correlation between the degree of disease activity and the amount of spontaneous incorporation of 3H-thymidine by B cells; the magnitude of the increase in frequency of spontaneous Ig-secreting cells in peripheral blood correlated strikingly with certain clinical features in these patients. Our findings suggest that there is heterogeneity of B cell hyperactivity in individual patients with SLE and, thus, that clinical subsets of SLE can be identified on the basis of B cell hyperactivity.

Adolescent↗

Activation of brain function by S-135, a benzodiazepine receptor inverse agonist.

1. S-135, 2-(5-methylthien-3-yl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinoline-3- one, bind binds to benzodiazepine receptors with a high affinity and shows pharmacological actions opposite to those of conventional benzodiazepine drugs. 2. S-135 induced no convulsion in mice by itself, but selectively potentiated the effect of subconvulsive dose of pentylenetetrazole. 3. S-135 potentiated rat crossed extensor reflex and Ro 15-1788 completely antagonized this potentiation. 4. S-135 antagonized pentobarbital-induced anesthesia, tetrabenazine-induced ptosis and reserpine-induced hypoactivity and shortened immobilization time in the despair test in mice, indicating that this compound possesses antidepressive properties. 5. S-135 antagonized amnesia in mice and rats in passive avoidance tasks. 6. Glucose utilization in brain areas relating to memory and arousal functions was enhanced following S-135 treatment. 7. These results indicate that S-135 can be a useful drug for activating depressed brain function.

Animals↗

Thienylpyrazoloquinolines: potent agonists and inverse agonists to benzodiazepine receptors.

Synthesis and structure-activity relationships of a series of 2-(thien-3-yl)- and 2-(thien-2-yl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-ones are reported. A number of the compounds possessed 1 order of magnitude higher affinity for the receptors than diazepam. Planarity was one of the structural requirements for binding to benzodiazepine receptors. The activities of agonists and inverse agonists were assessed on the basis of inhibition or facilitation of the pentylenetetrazole-induced convulsions, respectively. Thien-3-yl compounds exhibited inverse agonist activity whereas thien-2-yl analogues with a 5'-alkyl group showed agonist activity. Substitution on the quinoline moiety did not enhance in vivo activity. The most potent compounds were the 5-methylthien-3-yl derivative 6a as an inverse agonist and the 5-methylthien-2-yl compound 13a as an agonist.

Animals↗

Pressure wave with apnoea evaluated by sleep level in patient with ventricular dilation.

Seventeen patients who were suspected of having hydrocephalus, because of ventricular dilation from various causes, were included in this study of the pathophysiologic basis of the appearance of pressure waves (PWs). Pressure waves accompanied by apnoeas originated in arousal responses in the resting state of these patients. Frequent fits of apnoea were included in the entire sleep apnoea syndrome. Most pressure waves characteristically appeared in the state of non-REM sleep. During the appearance of such pressure oscillations, intracranial pressure was elevated transiently. This coincidence in the appearance of pressure oscillations with sleep apnoea was the most characteristic pathophysiologic result from this polygraphic study of the patients.

Adult↗

Alterations to the vascular vasodepressor prostaglandin system in DOCA-salt hypertensive rats and their enzymatic analysis.

To define the roles of vascular prostacyclin (PGI2) synthase for PGI2 generation in deoxycorticosterone acetate (DOCA)-salt hypertension, we investigated PGI2 synthase, phospholipase A2 and phospholipase C activities in the aortic wall of DOCA-salt prehypertensive and established hypertensive rats. Vascular PGI2 generation in the DOCA-salt hypertensive rats was increased by 91%, and was associated with an 88% increase in PGI2 synthase activity and lowered phospholipase C and A2 activity. In the prehypertensive stage, DOCA-salt rats showed reduced vascular PGI2 generation. Prostacyclin synthase activity was equal to that of controls. These data clearly suggest that DOCA-salt hypertensive rats increase their vascular PGI2 generation when they develop hypertension, and that this may be due to the activation of vascular PGI2 synthase.

Animals↗

Impairment of superoxide release by alveolar macrophage in rats exposed to oxygen and vitamin E.

We examined the digitonin-stimulated release of superoxide by alveolar macrophages (AMs) from young rats exposed to greater than 95% oxygen for 24-168 h. AMS were obtained by lung lavages, and the release of superoxide stimulated by digitonin was measured by using cytochrome C reduction. The total cell count of lung lavages decreased at 24 and 168 h of oxygen exposure (p less than 0.05 for both). The contamination of polymorphonuclear cells (PMNs) was less than 1% up to 120 h of oxygen exposure, and at 168 h PMNs increased to 5% of total cells in lung lavages. The viability of AMs was greater than 95% up to 72 h and then decreased to 90% at 120 h of oxygen exposure and 87% at 168 h. Digitonin-stimulated superoxide release by AMs recovered from lung lavages in rats exposed to hyperoxia showed a slight increase during the first 48 h. However, oxygen exposure for 72 h or more caused a significant decrease of the stimulated superoxide release of AMs compared to AMs from control rats. This decline in stimulated superoxide release of AMs resulting from hyperoxia was not prevented by vitamin E treatment.

Animals↗

Chemonucleolysis--an experimental histopathological study.

To investigate the histopathological changes of the intervertebral disc after chemonucleolysis, experiments were performed on 21 monkeys. After the injection of chymopapain, animals were sacrificed at definite intervals up to 1 year. Histopathological studies on these specimens revealed disappearance of proteoglycan from the nucleus pulposus, inner annulus fibrosus and cartilaginous endplates as early as 1 day after injection. At 4 weeks, regeneration of proteoglycan was indicated by the recovery of positive Safranin-O (S-O) staining in the area of the nucleus pulposus. After 24 weeks, the entire intervertebral disc showed uniform S-O staining indicating further regeneration of proteoglycan. The matrix of the reformed nucleus pulposus contained increased amount of fibrous elements compared to the controls. These results indicate proteoglycan regeneration by chondrocytes after chemonucleolysis. The reformed nucleus was histopathologically different from the control.

Animals↗