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Biomedical subjects

O Shinohara

Publications and source records attributed to O Shinohara.

28 records · Page 2Linked to original sources
PubMed1991

Allogeneic bone marrow transplantation in childhood leukemia.

Allogeneic bone marrow transplantation was performed in 94 patients with hematologic malignancies or other various diseases during the period between March 1982 and November 1990 at Tokai University Hospital. Projected disease-free survival rates of HLA genotypically identical marrow recipients were 88.9% for chronic myeloid leukemia transplanted in the first chronic phase (N = 9), 90.9% for acute leukemia in the first complete remission (N = 15), 54.5% for acute leukemia in later remissions (N = 14), 62.5% for solid tumors (N = 8) and 0% for patients transplanted in relapse (N = 7). The rate for HLA-mismatched marrow recipients with leukemia was 27.8% (N = 16). For patients with non-neoplastic diseases it was 100% regardless of HLA-compatibility (N = 26). The quality of life in long-term surviving pediatric marrow recipients has been acceptable. Common abnormalities among survivors are long-lasting hypogonadism due to radiation and subclinical impairment of lung function in the first year post-BMT. About two-thirds of children experienced a transient decrease in growth velocity in the immediate posttransplant period.

Acute Disease↗
PubMed1986

Activation of protein kinase C potentiates cyclic AMP production and stimulates steroidogenesis in differentiated ovarian granulosa cells.

Gonadotropin-stimulated steroidogenesis in the differentiating ovarian granulosa cell is mediated through the activation of cAMP-dependent protein kinase, and is also modulated by calcium-dependent mechanisms. Granulosa cells contain calcium-activated, phospholipid-dependent protein kinase (C kinase), and show an increase in phosphatidylinositol turnover in response to GnRH agonist analogs. To evaluate the role of C kinase in ovarian steroidogenesis, the potent phorbol ester, TPA, and the permeant diacylglycerol, OAG, were used to activate C kinase in granulosa cells from PMSG-treated immature rats. Both TPA and OAG caused dose-dependent stimulation of progesterone production without affecting intra- or extracellular cAMP levels. However, the maximum steroid responses to these compounds were less than those stimulated by cAMP. The ED50 for TPA-stimulated progesterone production was 3 nM, which is close to the known Km for activation of C kinase. Stimulation of steroidogenesis was only observed with biologically-active phorbol esters and permeant diacylglycerols such as OAG and DOG. Exposure of granulosa cells to phospholipase C also increased progesterone production in a dose-dependent manner without changing the cAMP content. Although TPA and OAG did not increase basal cAMP production, both agents enhanced the cAMP responses stimulated by hCG and forskolin; likewise, phospholipase C alone did not change cAMP production but caused a dose-dependent increase in the cAMP responses to hCG and forskolin. These results demonstrate that activation of C kinase promotes steroidogenesis in ovarian granulosa cells, and potentiates the activation of adenylate cyclase by hCG and forskolin. Such findings support the possibility that the calcium, phospholipid-dependent enzyme could be involved in the regulation of progesterone production by hormonal ligands such as gonadotropins and GnRH.

Animals↗
PubMed1986

Biosynthesis of cellular and secreted proteins during follicle-stimulating hormone-induced granulosa cell differentiation.

The synthesis of cellular and secreted proteins by differentiating granulosa cells from diethylstilbestrol-treated immature rats was studied by one- and two-dimensional polyacrylamide gel electrophoresis. In cultured granulosa cells, FSH altered the relative biosynthesis of specific cellular and secreted proteins in a concentration- and time-dependent manner. The incorporation of [35S]methionine into cellular proteins of Mr 42,000, 48,000, and 58,000 was enhanced by increasing amounts of the gonadotropin, whereas the labeling of a 44,000 Mr protein was reduced. Similarly, FSH increased the labeling of secreted proteins with relative Mr of 16,000, 17,000, 20,000, 25,000, 36,000, 41,000, 46,000, 111,000, and 153,000, and decreased that of proteins with Mr of 38,000, 48,000, 191,000, and 250,000. The expression of specific proteins was related to the degree of cellular maturation, since some proteins were newly synthesized during the early stages of granulosa cell development (less than 6 h), whereas others were more evident in the middle (24 h) or later (48 h) phases of culture. Also, the level of specific protein synthesis was variable since certain proteins were progressively produced during culture, and the biosynthesis of others fluctuated or was reduced during development. The effects of FSH on protein synthesis were mimicked by other cAMP-inducing ligands, including cholera toxin, forskolin, and 8-bromo-cAMP. Removal of FSH at 24 h of culture was followed by reversion of the protein biosynthetic pattern at 48 h to that of control cells, indicating that continued exposure to the gonadotropin is required during development. Cells cultured in the absence of ligands for 24 h synthesized proteins characteristic of differentiated cells when subsequently cultured with forskolin. These results indicate that FSH selectively alters the biosynthesis of cell-associated and secreted proteins during granulosa cell maturation. The characterization of these gene products and the mechanisms controlling their expression should ultimately clarify the sequential events involved in the hormonal regulation of granulosa cell development.

Animals↗
PubMed1985

Differential actions of phorbol ester and diacylglycerol on inhibition of granulosa cell maturation.

Hormonal induction of granulosa cell maturation is inhibited by phorbol esters and permeant synthetic diacylglycerols, but these activators of protein kinase C differ in their effects on cAMP production and actions. Both agents prevented the induction of luteinizing hormone receptors and progesterone biosynthesis by follicle-stimulating hormone, choleragen, and forskolin, but only diacylglycerol abolished the cAMP responses to these stimuli. Granulosa cell aggregation and aromatase activity were inhibited by phorbol ester but not completely by diacylglycerol. In intact granulosa cells, cytosolic C kinase activity was rapidly decreased by phorbol ester but unaffected by diacylglycerol. Although diacylglycerol has a marked inhibitory action on cAMP production, the more prominent suppression of granulosa cell differentiation by phorbol ester may be related to its rapid and prolonged action on kinase C.

Animals↗
PubMed1985

Gonadotropin-releasing hormone as a modulator of ovarian function.

GnRH and its agonist analogs exert direct inhibitory and stimulatory effects on the ovaries of animals from several species. In the immature follicle, GnRH inhibits the actions of FSH on an integrated array of biochemical responses that lead to follicular development and corpus luteum formation. GnRH also suppresses gonadotropin action in mature follicles, and stimulates certain ovarian processes such as steroidogenesis and oocyte maturation. The inhibitory and stimulatory effects of GnRH are mediated through the binding of the peptide to high-affinity receptors in granulosa and thecal cells. Recent studies have shown that GnRH action in the ovary is dependent upon calcium mobilization and probably operates through stimulation of phospholipid turnover and activation of protein kinase C.

Animals↗
PubMed1985

Inhibition of gonadotropin-induced granulosa cell differentiation by activation of protein kinase C.

The induction of granulosa cell differentiation by follicle-stimulating hormone (FSH) is characterized by cellular aggregation, expression of luteinizing hormone (LH) receptors, and biosynthesis of steroidogenic enzymes. These actions of FSH are mediated by activation of adenylate cyclase and cAMP-dependent protein kinase and can be mimicked by choleragen, forskolin, and cAMP analogs. Gonadotropin releasing hormone (GnRH) agonists inhibit these maturation responses in a calcium-dependent manner and promote phosphoinositide turnover. The phorbol ester phorbol 12-myristate 13-acetate (PMA) also prevented FSH-induced cell aggregation and suppressed cAMP formation, LH receptor expression, and progesterone production, with an ID50 of 0.2 nM. In FSH-treated cells, PMA did not reduce the initial increase in cAMP formation during the first 24 hr of culture but prevented its secondary increase from 24 to 48 hr. PMA also inhibited LH receptor induction by cholera toxin, forskolin, and 8-bromo-cAMP, but it did not impair cAMP responses to the former two agents, indicating that the site of action of the phorbol ester is distal to adenylate cyclase. The early stimulation of cAMP-dependent protein kinase activity by FSH was also unaffected by PMA, consistent with its lack of effect on the initial cAMP response to FSH. However, PMA caused a marked decrease in cytosolic protein kinase C activity within 1 min of its addition to the cells. The permeant diacylglycerols, 1-oleoyl-2-acetoyl-sn-glycerol and sn-1,2-dioctanoyl glycerol, also inhibited LH receptor formation, while the nonpermeant diacylglycerol, diolein, was inactive. These results indicate that in situ activation of protein kinase C by PMA or permeant diacylglycerols inhibits cAMP-dependent granulosa cell differentiation, and suggest that the inhibitory actions of GnRH agonists on granulosa cell maturation are also mediated by protein kinase C.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1983

Effects of chronic administration of delta-9-tetrahydrocannabinol on early embryogenesis of the mouse.

The effects of chronic administration of delta-9-tetrahydrocannabinol (THC), the major psychoactive component of marihuana, on embryogenesis were investigated in the mouse treated with THC prior to sexual maturation. The study was designed to imitate the prolonged abuse of marihuana by sexually immature and adolescent girls. Female Swiss-Webster mice were injected, intraperitoneally, with THC 5 mg/kg per day or with the vehicle for 21 consecutive days, starting on the 30th day of life, which is prior to their sexual maturation. The dose of THC was approximately equivalent to that absorbed by a man smoking 1 to 2 marihuana cigarettes per day. Superovulation was then induced, and the mice were mated with untreated males. Ova were recovered from the oviducts just prior to the first cleavage division, and at about the time of the second cleavage division. The incidence of degenerative ova increased from 13.6% in the controls to 19.1% in the THC-treated group (P less than 0.001) at the time of the second cleavage division, but there was no difference in the incidence of morphologically abnormal ova between the two groups just prior to the first cleavage division. The rate of successful completion of the first cleavage division, but not the second cleavage division, was adversely affected by THC, resulting in accumulation of morphologically abnormal ova at the later stage. In view of the known disruptive effect of THC on the process of cell division, it was postulated that THC might have adversely affected meiosis, leading to the inability of the ova to undergo the first cleavage division.

Animals↗