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Biomedical subjects

Y W Lin

Publications and source records attributed to Y W Lin.

83 records · Page 5Linked to original sources

Retinoblastoma in dizygotic twins born as extremely low birth weight infants.

A case of bilateral retinoblastoma affecting both of a pair of dizygotic twins was reported. To our knowledge, there has been only one previous report of dizygotic twins, both affected, with this disease. The present twins had no family history of retinoblastoma. They were born prematurely as extremely low birth weight infants after 26 weeks and 4 days of gestation, and 3 of the 4 tumors were detected at 33 weeks after conception. Using LINAC external radiation therapy followed by xenon photocoagulation when necessary, the tumors were successfully treated. These cases show that retinoblastoma can develop in the pre-term period, indicating that the second mutation involved in tumorigenesis can occur in the fetus.

Diseases in Twins↗

Familial juvenile nephronophthisis in two siblings--histological findings at an early stage.

We present two female siblings with familial juvenile nephronophthisis (FJN) which was diagnosed at the early stage of renal failure. Diagnosis was made during the investigation of anemia in case 1 and by a subsequent family survey in case 2. Most patients with FJN are not identified until the terminal stage of renal failure and such cases have rarely been reported in Japan. Case 2 had a reduction in the maximum urinary concentration ability but no azotemia, and among the FJN patients reported in Japan so far she has the least advanced renal disease. Histological examination of the renal biopsy in case 1 showed typical findings of FJN, such as thickening and lamination of the tubular basement membrane (TBM), interstitial fibrosis, and round cell infiltration of the interstitium. In case 2, renal biopsy revealed an irregular marked thickening of the TBM with trivial interstitial changes and a normal glomerular appearance. The histology of these two cases suggests that the TBM may be the primary site affected in FJN.

Child↗

Steroidogenesis in Fundulus heteroclitus. I. Production of 17 alpha-hydroxy,20 beta-dihydroprogesterone, testosterone, and 17 beta-estradiol by prematurational follicles in vitro.

In order to understand better the mechanism of gonadotropin action on steroidogenesis in prematurational follicles of Fundulus heteroclitus, follicle synthesis of 17 alpha-hydroxy, 20 beta-dihydroprogesterone (17 alpha-OH,20 beta-DHP), testosterone (T), and 17 beta-estradiol (E2) from a variety of precursors and the maturational response of oocytes were simultaneously followed in vitro. The addition of 25-hydroxycholesterol, pregnenolone, or progesterone to unstimulated follicles increased media 17 alpha-OH,20 beta-DHP, T, and E2, as well as oocyte germinal vesicle breakdown (GVBD) in a dose-dependent manner. Inhibition of cholesterol side-chain cleavage by aminoglutethimide blocked 25-hydroxycholesterol-promoted steroid accumulation and GVBD, indicating that 25-hydroxycholesterol does not directly induce GVBD, but rather is metabolized in the follicle to an active steroid (presumably 17 alpha-OH,20 beta-DHP). Likewise, trilostane, an inhibitor of delta 5-3 beta-hydroxysteroid dehydrogenase, blocked pregnenolone action. Both inhibitors also completely abolished steroid accumulation and GVBD promoted by a F. heteroclitus pituitary extract (FPE), but not GVBD induced by exogenous 17 alpha-OH,20 beta-DHP. FPE also significantly depressed T but enhanced E2 production from exogenous precursors. We have concluded from these observations that (1) cholesterol side-chain cleavage and pregnenolone conversion to progesterone are essential for gonadotropin-promoted follicle steroid production and the resulting reinitiation of meiosis by the oocyte, (2) the enzymes necessary for the conversion of cholesterol to 17 alpha-OH,20 beta-DHP, T, and E2 are present in the unstimulated, prematurational follicle, and (3) gonadotropin initiates steroidogenesis by acting at a step prior to the conversion of cholesterol to pregnenolone; it also appears to enhance aromatase activity.

20-alpha-Dihydroprogesterone↗

Steroidogenesis in Fundulus heteroclitus. II. Production of 17 alpha-hydroxy-20 beta-dihydroprogesterone, testosterone, and 17 beta-estradiol by various components of the ovarian follicle.

Fundulus heteroclitus prematurational follicles (1.3-1.4 mm) were dissected into various components and cultured in vitro to examine the type of cells involved in the synthesis of steroids upon F. heteroclitus pituitary extract (FPE) stimulation or addition of exogenous precursors (25-hydroxycholesterol or pregnenolone). Culture media and follicular tissue extracts were assayed for 17 alpha-hydroxy-20 beta-dihydroprogesterone (17 alpha-OH.20 beta-DHP), testosterone (T), and 17 beta-estradiol (E2) content using specific radioimmunoassays. Complete removal of the follicle wall (denuded oocytes) eliminated steroid accumulation induced by FPE treatment. Removal of the theca/epithelium layer (defolliculated oocytes) did not affect the steroidogenic response (17 alpha-OH,20 beta-DHP, T, E2 production) of the follicles to FPE or exogeneously added precursors (25-hydroxycholesterol or pregnenolone). Isolated theca/epithelium layers secreted only T. Isolated follicular preparations that did not contain the oocyte (theca/epithelium layers or follicle cells) secreted higher levels of steroids to the culture media than did intact follicles. We conclude from these results that (1) the follicle cells (granulosa cells) are the primary source of the various steroids produced by the F. heteroclitus ovarian follicle in response to FPE stimulation: (2) the synthesis of 17 alpha-OH,20 beta-DHP and E2 does not require the involvement of two cell types as shown in other teleosts; (3) the theca/epithelium layer is able to produce T but lacks the aromatase activity necessary for E2 synthesis; and (4) steroids synthesized in the follicle wall are both secreted to the medium and accumulated in the oocyte.

20-alpha-Dihydroprogesterone↗

Fundulus heteroclitus gonadotropin(s). I. Homologous bioassay using oocyte maturation and steroid production by isolated ovarian follicles.

Isolated ovarian follicles from several species were cultured to develop an in vitro bioassay system for Fundulus heteroclitus gonadotropin. An extract of F. heteroclitus pituitaries, when tested in heterologous systems using follicles from Rana pipiens. Xenopus laevis, and Carassius auratus, was ineffective in provoking either germinal vesicle breakdown or steroid production. In a homologous system using F. heteroclitus follicles, F. heteroclitus pituitary extract was capable of inducing both germinal vesicle breakdown and steroid production in a dose-dependent fashion. Testosterone, estradiol-17 beta, and 17 alpha-hydroxy,20 beta-dihydroprogesterone were detected in both the culture media and the follicle extracts after F. heteroclitus pituitary extract stimulation. The steroidogenic responses resulting from the pituitary extract stimulation were dependent on the size and stage of follicular development. Only large vitellogenic follicles (1.2-1.4 mm diameter) were able to produce 17 alpha-hydroxy,20 beta-dihydroprogesterone and testosterone. Small vitellogenic follicles (less than 1.2 mm) were unresponsive to stimulation by F. heteroclitus pituitary extracts as scored by either germinal vesicle breakdown or production of 17 alpha-hydroxy, 20 beta-dihydroprogesterone and testosterone. However, estradiol-17 beta production was detected in follicles of a much wider size range: Follicles as small as 0.8 mm diameter were responsive to F. heteroclitus pituitary extract stimulation and produced a large quantity of estradiol-17 beta. There was a marked seasonal sensitivity of F. heteroclitus follicles to pituitary extract stimulation in vitro. Follicles obtained from fish outside of the breeding season (January) were less responsive to stimulation by pituitary extract or steroid. The same preparation of pituitary extract was capable of provoking germinal vesicle breakdown in follicles obtained in May. Pituitary extracts prepared during October through January were also less potent than those prepared during the breeding season (February through September). We conclude that F. heteroclitus gonadotropin(s) shows a noticeable species specificity and that F. heteroclitus follicles exhibit both a season- and a size-dependent responsiveness to gonadotropin(s). Hence, with a judicious use of the appropriate types of F. heteroclitus ovarian follicles, we have been able to demonstrate that in vitro oocyte maturation and steroid production are sensitive, homologous bioassays for F. heteroclitus gonadotropin(s).

Animals↗

Intrafollicular action of estrogen in regulating pituitary-induced ovarian progesterone synthesis and oocyte maturation in Rana pipiens: temporal relationship and locus of action.

Previous studies demonstrated that estrogen inhibited frog pituitary homogenate (FPH) and progesterone-induced oocyte maturation. In order to determine whether estrogen interfered with intrafollicular progesterone synthesis, experiments were designed to study the effect of exogenous estrogen (estradiol-17 beta) on FPH-induced progesterone production in amphibian (Rana pipiens) ovarian follicles cultured in vitro. Intrafollicular progesterone concentrations were monitored directly using radioimmunoassay and the occurrence of germinal vesicle breakdown (GVBD) was used as a biological indicator of the action of steroids on oocyte maturation. FPH elicited a rapid and dramatic increase in follicular progesterone concentration (1000-3000 pg per follicle) which preceded germinal vesicle breakdown. Addition of estrogen to the culture medium inhibited FPH-induced progesterone production and the accompanying GVBD in a dose-dependent fashion. The presence of estrogen did not enhance the degradation of preloaded progesterone, suggesting estrogen impeded progesterone synthesis rather than enhanced progesterone metabolism. The temporal relationship between estrogen and FPH interaction was assessed by varying the relative time of hormone addition, after which intrafollicular progesterone concentration and GVBD were monitored. Progesterone production and GVBD were drastically inhibited when estrogen was added before or simultaneously with FPH. However, when addition of estrogen was delayed until after FPH simulation, a progressive loss of the inhibitory effect of the steroid on progesterone accumulation and GVBD was observed. Thus, the estrogen-sensitive phase was confined to the early portion of FPH stimulation. Continuous presence of estrogen in the culture system was not required to inhibit FPH-induced events. A short exposure (15 min) of follicles to estrogen was sufficient to inhibit oocyte maturation, whereas progesterone synthesis was not significantly affected. With longer exposure, however, FPH-induced progesterone production was impeded. Washing estrogen-treated follicles did not reverse the inhibitory effect of estrogen, however the follicles remained responsive to exogenous progesterone stimulation and exhibited GVBD. Results suggest that the inhibitory effects of estrogen on FPH action and progesterone production were not reversible under the in vitro culture conditions. To determine whether specific follicular components were involved in estrogen inhibition, progesterone production was assessed following selective removal of different follicle components by microdissection prior to being treated with FPH and estrogen.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

In vitro estrogen modulation of pituitary and progesterone-induced oocyte maturation in Rana pipiens.

The role of estrogen in the process of hormone-induced meiotic maturation was investigated using in vitro culture of Rana pipiens ovarian follicles and isolated oocytes. Estrogen alone was ineffective in triggering maturation and did not act synergistically when combined with progesterone. Instead, slight inhibitory effects on oocyte maturation were observed when estrogen was added to the culture medium simultaneously with progesterone. Prolonged estrogen pretreatment (1-8 hr) was seen to be increasingly effective in inhibiting progesterone-induced germinal vesicle breakdown (GVBD). Washing follicles after estrogen pretreatment diminished the inhibitory effects, suggesting continued presence of estrogen was necessary for maximal inhibition. Progesterone-induced GVBD was inhibited by estrogen in denuded oocytes (follicle wall removed) indicating that estrogen acts directly on the oocyte. Incorporation of radioactive progesterone into ovarian follicles was not inhibited regardless of the estrogen concentration used. This suggests that estrogen inhibits oocyte maturation by raising intrafollicular threshold to progesterone rather than by suppressing hormone incorporation into ovarian follicles. Next, the action of estrogen on frog pituitary homogenate (FPH)-induced GVBD was examined although both progesterone and FPH-induced GVBD were inhibited by estrogen, the latter was remarkably more susceptible and did not require estrogen pretreatment. Furthermore, increased concentration of progesterone, but not FPH, overcame the inhibitory action of estrogen. The results suggest that estrogen may exert its inhibitory effects on gonadotropin action at more than one site. Estrogen can modulate either the maturation-inducing action of progesterone directly at the oocyte level or the suppression of progesterone production by the follicle cell. Hence, estrogen may play an important role as an endogenous regulator of oocyte meiotic maturation.

Animals↗