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T Oka

Publications and source records attributed to T Oka.

At least 1,261 records · Page 70Linked to original sources
PubMed1983

The differential actions of cortisol on the synthesis and turnover of alpha-lactalbumin and casein and on accumulation of their mRNA in mouse mammary gland in organ culture.

Cortisol was previously shown to exert different, concentration-dependent, effects on the accumulation of casein and alpha-lactalbumin in mammary glands from mid-pregnant mice cultured in the presence of insulin and prolactin [Ono & Oka (1980) Cell 19, 473-480]. The present study demonstrated that the addition of 30nM-cortisol to the medium containing insulin and prolactin resulted in a marked enhancement of the rate of synthesis of both alpha-lactalbumin and casein in cultured tissue. The addition of 3 microM-cortisol in combination with insulin and prolactin caused a marked decrease in the rate of alpha-lactalbumin synthesis, but increased casein synthesis substantially. Similar changes were also observed in the amount of translatable mRNA for alpha-lactalbumin and casein in mammary explants cultured with insulin, prolactin and the two concentrations of cortisol. The study of the turnover of the milk proteins in cultured explants showed that virtually all of the casein synthesized remained intact in tissue explants cultured with 3 microM cortisol, whereas about 45% of casein disappeared in 40h from explants cultured with 30nM-cortisol. In contrast, the two concentrations of cortisol did not differentially affect the disappearance of alpha-lactalbumin, which was about 55% in 40h. These results indicate that the concentration-dependent differential actions of cortisol on the accumulation of alpha-lactalbumin and casein are exerted through its effects on the rate of synthesis and turnover of the two proteins as well as on the accumulation of their mRNA species.

Animals↗
PubMed1983

The interaction of cortisol and prostaglandins on the phenotypic expression of the alpha-lactalbumin gene in the mouse mammary gland in culture.

Addition of cortisol at concentrations above 300 nM selectively inhibited the synthesis of alpha-lactalbumin and the accumulation of its mRNA in the mouse mammary gland cultured in the presence of insulin and prolactin, whereas the same treatment augmented casein synthesis and the accumulation of casein mRNA. Prostaglandin E2 or F2 alpha reversed the inhibitory effects of cortisol in a dose-dependent manner, without affecting casein production. The levels of prostaglandin E2 or F2 alpha in tissue explants cultured with insulin and prolactin increased about 2.6-fold over those in uncultured tissue, and the addition of cortisol decreased these levels approximately 2-fold. These results indicate the ability of prostaglandins to counteract the inhibitory effect of cortisol on the alpha-lactalbumin gene expression in the mouse mammary gland.

Animals↗
PubMed1983

Involvement of collagen formation in the hormonally induced functional differentiation of mouse mammary gland in organ culture.

In mammary gland organ culture from midpregnant mice, synergistic actions of insulin, cortisol, and prolactin stimulate differentiation of mammary epithelium and induce the synthesis of the milk proteins casein and alpha-lactalbumin. In the present study we examined the production of collagen and its function in the hormone-dependent development of mammary gland in vitro. The measurement of collagen production by the hydroxyproline assay and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that the accumulation of collagen type I and type III in cultured mammary explants increased with the addition of insulin, cortisol, and prolactin to a chemically defined medium. When an analog of proline, L-azetidine-2-carboxylic acid (LACA), was added at a concentration of 80 microgram/ml with insulin, cortisol, and prolactin at the beginning of culture, collagen production in cultured tissue was inhibited by 75% during a 3-day incubation period. This agent also inhibited the synthesis of casein and alpha-lactalbumin by about 77 and 70%, respectively. The inhibitory effect of LACA could be prevented by L-proline; concomitant addition of L-proline (80 microgram/ml) with LACA (80 microgram/ml) resulted in complete restoration of milk protein synthesis to normal levels. Measurement of the amount of milk protein mRNAs in mammary explants by a cell-free translation assay demonstrated that LACA reduced the hormone-stimulated accumulation of casein mRNA and alpha-lactalbumin mRNA by 79 and 76%, respectively. LACA, however, produced little inhibition of DNA synthesis in cultured tissue. These results suggest that collagen production may be involved in the phenotypic expression of milk protein genes during hormonal induction of mammary epithelial differentiation in vitro.

Animals↗
PubMed1983

Possible physiological role of epidermal growth factor in the development of the mouse mammary gland during pregnancy.

Epidermal growth factor stimulated cell proliferation in a primary mammary epithelial cell culture derived from mice at different stages of pregnancy. Moreover, the peptide hormone inhibited casein production induced by the synergistic actions of insulin, cortisol and prolactin. The inhibitory effect of epidermal growth factor was influenced by the gestational stages of the mammary gland. These effects of epidermal growth factor were exerted at physiological concentrations. The dual actions of epidermal growth factor on mammary cells implicate its participation in regulation of the growth and differentiation of the mammary gland during pregnancy.

Animals↗
PubMed1983

Spontaneous blastogenesis assay for detection of renal allograft rejection in man.

In attempts to assess the possibility of allograft rejection, serial assays of spontaneous blastogenesis (SB) by uptake of tritium thymidine in 50 microliters whole blood were performed in 72 consecutive renal allograft recipients. Of 79 clinically diagnosed rejection episodes, 65 (82 per cent) had an associated elevation of SB values, and 14 (18 per cent) showed false negative results. In 38 (59 per cent) of 65 episodes in which the elevations of SB values were observed, the elevations preceded the clinical diagnosis by 1-7 days. Although large doses of steroids did not affect the values of SB, false positive elevations which were mainly caused by systemic infections occurred in 12 cases. There was no significant association between severity of rejection crisis and the maximum value of SB in the course. The SB assay requiring only a small amount of blood can be accomplished within 4-5 hours and provides a simple means of assessing and predicting host's immune responsiveness to the histocompatibility antigens.

Graft Rejection↗
PubMed1983

Analysis of data on 170 consecutive patients transplanted with kidneys from living relatives.

Graft survival, mortality, histocompatibility and rehabilitation were studied in 170 consecutive patients receiving kidneys from living relatives. Average follow-up was 5 years and one month with a minimum post-transplant evaluation of 6 months. Overall patient survival was 93 per cent at one year and there was a remarkable decline thereafter. Overall graft survival was 84 per cent at one year, 73 per cent at three, and 67 per cent at five years. Among the 76 patients treated since 1979, both patients and graft survival have improved: 93 per cent and 80 per cent at three years, respectively, because of a decrease in serious complications. Although no correlation was found between HLA-A and B loci matching and graft survival in patients with no mismatch in the HLA-DR locus, there was a significantly higher graft survival. Infection, the leading cause of death especially in the early post-transplant period, has been brought under control. Aseptic necrosis of the femoral head which occurred in 27 (16 per cent) patients proved to be the most difficult problem. The majority of patients are functioning well socially and vocationally and reproductive functions have been restored. Transplantation offers a better quality of life for patients with chronic renal failure, as compared to hemodialysis. The increased procurement of cadaver kidneys must be given attention.

Adolescent↗
PubMed1983

The choice of opioid receptor subtype in isolated preparations by dynorphins.

The choice of opioid receptor subtype by dynorphins was studied in isolated preparations. Both dynorphin-(1-17) and dynorphin-(1-8) had significant inhibitory actions on the electrically evoked contractions of guinea-pig ileum, mouse vas deferens and rabbit ileum. The inhibition of contractions by dynorphin-(1-17) in three preparations was antagonized more effectively by Mr 2266 which had a high affinity to both mu- and kappa-receptors, than naloxone which had a high affinity only to mu-receptors, indicating that dynorphin-(1-17) acted on kappa-receptors in three preparations. Additionally, the inhibitory potency of dynorphin-(1-17) relative to that of ethylketocyclazocine, a representative kappa-receptor agonist, in guinea-pig ileum was similar to that in either mouse vas deferens or rabbit ileum. This also suggested that dynorphin-(1-17) acted as a kappa-receptor agonist in three preparations. The effectiveness of naloxone and Mr 2266 to antagonize the agonist action of dynorphin-(1-8) indicated that dynorphin-(1-8) acted as a kappa-receptor agonist in either guinea-pig ileum or rabbit ileum whether or not peptidase inhibitors were existed while in mouse vas deferens it acted as a delta- or kappa-receptor agonist in the absence or presence of peptidase inhibitors, respectively. Thus, the choice of opioid receptor subtype in mouse vas deferens by dynorphin-(1-8) was likely to depend whether peptidases were inhibited or not. The inhibitory potency of dynorphin-(1-8) in the presence of peptidase inhibitors relative to that of ethylketocyclazocine in rabbit vas deferens, which had been shown to contain kappa-receptors exclusively, was similar to that in either mouse vas deferens or rabbit ileum, but was significantly different from that in guinea-pig ileum. This indicates that kappa-receptors in guinea-pig ileum are different from those in other preparations although the possibility of other causes such as incomplete inhibition of peptidase(s) can not be neglected.

Animals↗
PubMed1983

Contribution of maternal mRNA for maintenance of Ca2+-dependent reaggregating activity in dissociated cells of Xenopus laevis embryos.

Dissociated Xenopus laevis blastula cells, where reaggregation was inhibited in Ca2+-free medium, reaggregated immediately after the addition of Ca2+. This reaggregation was not inhibited by cordycepin or actinomycin D treatment during culture, although cycloheximide and puromycin were inhibitory. The reaggregation was not inhibited even when fertilized eggs were microinjected with cordycepin and their RNA synthesis was continuously inhibited through cleavage to blastula stages. In neurula cells, cordycepin treatment induced significant reduction in sizes of aggregates formed. These results suggest that the Ca2+-dependent reaggregating activity of blastula cells is maintained by the translation of maternal, rather than newly synthesized, mRNA.

Animals↗
PubMed1983

Adsorption of mutagens to cotton bearing covalently bound trisulfo-copper-phthalocyanine.

A method for separating nonpolar mutagens from their dilute aqueous solutions is described. It utilizes the affinity of the mutagens to a phthalocyanine derivative attached to cotton through a covalent bond. For mutagens having 3 or more fused aromatic rings in their structures, efficient adsorption took place on soaking the cotton in their solutions. The mutagens adsorbed can be recovered by elution with ammoniacal methanol. Mutagenicity in smoker's urine, cooked beef, and river water was detected by use of this method.

Adsorption↗
PubMed1983

Effect of internal jugular vein ligation on resorption of cerebrospinal fluid.

The influence of jugular vein ligation on CSF resorption was examined experimentally by means of a manometric ventricular infusion test in dogs. Capacity of CSF absorption was decreased in a stepwise manner according to whether unilateral or bilateral ligation of jugular veins was performed. Interestingly, in addition to rises in ICP, dural sinus pressure was predominantly elevated after bilateral jugular ligation, often exceeding the ICP level. The CSF malresorption observed was considered to be closely related to the lowered pressure gradients between ICP and intracranial sinus pressure.

Animals↗
PubMed1983

Cortisol 21-mesylate exerts glucocorticoid action on the induction of milk protein synthesis in cultured mammary gland.

Cortisol 21-mesylate, an alkylating derivatives of cortisol, was previously shown to exert an anti-glucocorticoid action in rat hepatoma cell culture (Simons, Thompson and Johnson 1980). In this study the effect of cortisol 21-mesylate on milk protein synthesis induced in cultured mouse mammary gland by glucocorticoid, insulin, and prolactin was investigated. Addition of cortisol 21-mesylate at concentrations ranging from 10(-8) M to 10(-6) M produced no inhibition of casein synthesis that was induced by glucocorticoid, insulin and prolactin in mammary explants from midpregnant mice. On the other hand, cortisol 21-mesylate in combination with insulin and prolactin stimulated casein synthesis in cultured tissue. The potency of cortisol mesylate was about 1/10 to 1/30th of that of cortisol. Cortisol 21-mesylate, like cortisol, also augmented the accumulation of alpha-lactalbumin in midpregnant rat mammary tissue cultured in the presence of insulin and prolactin. A cell-free competition study of glucocorticoid receptors using cytoplasmic extracts from mouse mammary tissue showed that cortisol 21-mesylate competitively inhibited the binding of dexamethasone on glucocorticoid receptors. The apparent affinity of cortisol 21-mesylate for glucocorticoid receptors is about 1/10th of that of cortisol. These results indicate that cortisol 21-mesylate acts as a glucocorticoid but not as an antiglucocorticoid in the mammary gland.

Animals↗
PubMed1983

Tumor promoter 12-O-tetradecanoylphorbol 13-acetate, like epidermal growth factor, stimulates cell proliferation and inhibits differentiation of mouse mammary epithelial cells in culture.

12-O-Tetradecanoylphorbol 13-acetate (TPA) is a potent tumor promoter and shares several biological activities of epidermal growth factor (EGF). Recently we have shown that EGF stimulates DNA synthesis and inhibits milk protein synthesis induced by insulin, cortisol, and prolactin in a primary mouse mammary epithelial cell culture [Taketani, Y. & Oka, T. (1983) FEBS Lett., in press]. Using this system, we examined the biological action of TPA in reference to that of EGF. TPA stimulated cell proliferation and inhibited the synthesis of milk proteins casein and alpha-lactalbumin during a 5-day culture. The ED50 was about 2.5 ng/ml for DNA synthesis and 0.1 ng/ml for milk protein synthesis. Removal of TPA from the medium normalized DNA synthesis completely and casein synthesis partially. The ability of various TPA analogs to stimulate DNA synthesis and inhibit casein synthesis correlated with their potency as tumor promoters. Both TPA and EGF decreased the specific prolactin binding of cultured cells by approximately equal to 50%. These results indicate that TPA, like EGF, switches the developmental course of mammary epithelium from differentiation to proliferation.

Animals↗
PubMed1983

Biological action of epidermal growth factor and its functional receptors in normal mammary epithelial cells.

Normal murine mammary epithelial cells possessed the capacity to bind epidermal growth factor (EGF) in a specific and saturable manner. Scatchard plot analysis showed a curvilinear pattern. Assuming that this is not due to negative cooperativity of EGF binding, the data suggest the presence of two classes of receptors with a high and a low affinity: Kd values = 1 x 10(-10)M and 3.6 x 10(-9)M, respectively. The number of high- and low-affinity receptors was estimated to be 800 per cell and 8,600 per cell, respectively. The occupancy of EGF receptors for a half-maximal stimulation of DNA synthesis or inhibition of casein synthesis was about 10% and 6% of total receptors, respectively. A potent tumor promoter, 12-O-tetradecanoylphorbol 13-acetate, acted synergistically with EGF in terms of stimulation of DNA synthesis but not in terms of inhibition of casein synthesis when the two agents were added at a suboptimal concentration. The presence of the tumor promoter increased the amount of EGF bound to mammary cells in culture and also decreased a loss in the amount of EGF in the culture medium. These results indicate that mammary epithelial cells possess functional receptors for EGF, which are modulated by the tumor promoter.

Animals↗
PubMed1983

Effect of bleomycin on lipid peroxides, glutathione peroxidase and collagenase in cultured lung fibroblasts.

Bleomycin-Cu(II) complex tended to increase the lipid peroxide level in cultured lung fibroblasts, though neither free bleomycin nor free cupric ion increased the level. Simultaneous addition of DL-alpha-tocopherol decreased the level significantly. Bleomycin-Cu(II) complex decreased glutathione peroxidase activity remarkably, though free bleomycin reduced the activity only slightly. Collagenase activity was not decreased but rather increased by both free bleomycin and bleomycin-Cu(II) complex. Accordingly, the accumulation of collagen induced by bleomycin could be explained not by a decrease in collagenase activity, but by the occurrence of cross-linking of collagen due to the increased lipid peroxides.

Bleomycin↗
PubMed1983

Epidermal growth factor stimulates cell proliferation and inhibits functional differentiation of mouse mammary epithelial cells in culture.

Mouse mammary epithelial cells cultured on collagen gels multiplied and produced casein and alpha-lactalbumin in response to insulin, cortisol, and PRL. The addition of epidermal growth factor (EGF) at 50 ng/ml increased the total number of epithelial cells by 30-40% and thymidine incorporation into DNA 4.7-fold after 5 days of culture. In contrast, EGF inhibited hormonal induction of the synthesis of casein and alpha-lactalbumin in those cells by about 45% and 55%, respectively, without inhibiting total protein synthesis. Furthermore, EGF decreased casein mRNA activity by 55% and increased total mRNA activity by 66% in cells cultured with the three hormones. These effects of EGF were apparent at 0.1 ng/ml and were maximal at 50-100 ng/ml and could be reversed by its removal from the medium, followed by the addition of anti-EGF antibody. The inhibition of casein synthesis by EGF was unaffected by the concentrations of insulin, cortisol, and PRL. Other growth factors, such as fibroblast growth factor, multiplication-stimulating activity, nerve growth factor, and platelet-derived growth factor, did not simulate the effects of EGF. Cytarabine (1 microgram/ml), which inhibited thymidine incorporation into DNA by 94%, did not block the inhibitory action of EGF on casein synthesis. These results suggest that EGF serves as a regulator of hormone-dependent growth and differentiation of mammary epithelial cells.

Animals↗
PubMed1983

The effect of capsaicin on C-fiber reflex and heat evoked discharge in the acute spinal cat.

The effects of capsaicin were studied electrophysiologically on C-fiber reflex and heat-evoked discharge in adult spinal cats. The results can be summarized as follows: 1) 125 micrograms/Kg of capsaicin, administered intravenously, induced an increase in spontaneous discharge in the L7 ventral root; 2) 250 micrograms/Kg of capsaicin, administered intravenously, induced an increase in the C-fiber reflex response; 3) 125 micrograms/Kg of capsaicin, administered intravenously, induced an increase in the heat-evoked discharge; but 4) 25 micrograms/Kg of capsaicin, administered through the femoral artery, did not show significant alteration of the heat-evoked discharge. These findings suggest that capsaicin which produced a release of substance-P from primary afferent nerves may principally act on C-fiber and A delta-fiber. Capsaicin was much more effective on the heat-evoked discharge than on the C-fiber reflex when administered intravenously.

Afferent Pathways↗