Search PubMed⌕ Search

Biomedical subjects

Y C Lin

Publications and source records attributed to Y C Lin.

At least 235 records · Page 13Linked to original sources
PubMed1992

Morphometric analysis of renal cortex changes induced by diethylstilbestrol (DES) in Syrian hamsters.

Estrogen-induced renal adenocarcinoma usually can be readily detected in castrated hamsters after 9 to 12 months of DES treatment. In the present study, we examined the morphological characteristics of the renal cortices of castrated hamsters that had received 3 months of DES treatment in order to describe early histological evidence of carcinogenesis induction. Twelve Syrian Golden hamsters, 8 to 9 weeks of age, were first castrated and then subjected to either subpannicular implantation of a 20 mg DES pellet (experiment group), or sham operation (controls). Morphological and 2-D morphometric evaluations were conducted sequentially on kidney histological sections. Numbers (N's) or area fractions (AF's) of renal components in the juxta-medullary junction of each kidney section were processed for morphometric evaluation. The DES treatment caused a 15% increase in kidney weight, but not body weight. Dysplastic foci associated with hyperplastic tubules were present in 67% of the left kidneys or 17% of the right kidneys of hamsters in the test group, but were absent in kidneys of controls. DES treatment decreased glomeruli N by 33% and increased the vasculature AF by 169% per examination field. DES also increased AF's of glomeruli, proximal tubules, distal tubules, and vasculature by 17, 81, 53 and 346% per nephron, respectively. Our results showed that, after the first three months of DES-treatment, hamster kidneys developed dysplastic foci and their masses were greater than controls. Increased renal components in the juxta-medullary junction region included glomeruli, tubules, and vasculature. The dysplastic foci may be sites of subsequent malignancies, whereas the increased renal mass might be a result of functional adaptation/expression to exogenous estrogen which might contribute to the carcinogenic process.

Animals↗
PubMed1992

Murine leukemia virus induced central nervous system diseases.

The ts1 mutant of Moloney murine leukemia virus TB (MoMuLV-TB) causes a degenerative neurologic and immunologic disease in mice characterized by development of spongiform encephalomyelopathy that results in hind-limb paralysis, marked thymic atrophy associated with immunodeficiency, and generalized body wasting. T cells, particularly CD4+ helper T cells, play a key role in the pathogenesis of the disease induced by ts1. Therefore, ts1 is unique among the described murine retroviruses in its ability to afflict both the central nervous system (CNS) and the T-cell compartment of the immune system in the same host. This particular ability to cause degenerative diseases involving both the CNS and immune system is shared by the lentiviruses responsible for development of the acquired immunodeficiency syndromes of humans and macaques. Our goal has been to elucidate the specific cellular and molecular mechanisms that underlie this neuro- and immunopathogenicity of ts1. We have previously reported that the primary neuropathogenic determinant of ts1 maps to a single amino acid substitution, Val-25-Ile, in the precursor envelope protein gPr80env. Further, at the restrictive temperature, the Val-25-Ile substitution did not prevent oligomerization of the gPr80env proteins; however, the structure of the oligomer was incompetent for transport from the ER to the Golgi. These findings suggest that the cytopathic effect of ts1 in neural cells might be due to accumulation of the gPr80env oligomers in the ER. Since glial cells are targets of ts1 infection in vivo, primary astrocytic cultures were established and the cytopathic effect of ts1 and MoMuLV-TB on these cells assessed. Both viruses replicate well in astrocytes and their replication is cytopathic, albeit to different degrees. The ts1 mutant appears to produce greater cell killing than the wild-type virus. Furthermore, it was found that the rate of processing of gPr80env of ts1 in astrocytes is slower than that of MoMuLV-TB. Therefore, the inefficient transport and processing of gPr80env of ts1 appears to correlate with its cytopathic effect in these cells. Electron microscopic studies of the ts1-infected astrocytes revealed large numbers of aberrant particles in the ER. The in vitro cytopathic effect of ts1 on astrocytes may reflect what happens in vivo. An indirect mechanism of neuronal-cell killing by ts1 is proposed.

Animals↗
PubMed1992

Characteristics of covalent gossypol binding to microsomal proteins.

Gossypol is a potent antifertility agent contained in seeds and other parts of cotton plants. The limit set in 1974 by the FDA for this C30H30O8 compound in consumer products is 450 ppm. The binding characteristics and the nature of the microsomal protein adducts of radiolabeled gossypol were studied using centrifugation, extraction, reverse phase HPLC and filter assay approaches. Results showed a significant amount of radiolabeled gossypol to be associated with the precipitated proteins after aqueous, ethanol, acetone and ether extractions. The nature of binding of these protein adducts involved covalent, covalent but reversible (e.g., Schiff bases), and tightly-bound and trapped noncovalent residues. Non-acid labile binding adducts constituted 40% of the precipitated microsomal proteins. Eight percent of the adducts were covalent, reversible and reducible by NaBH4. A gradient HPLC separation of the acetone extracts resulted in non-gossypolone hydrophilic protein adducts with a mean retention time of 2.3 minutes. Gossypol can bind tightly to hepatic microsomal proteins with a ratio of 80 nmoles/mg protein under physiological conditions. Significant portions of these bindings are not due to simple acid labile Schiff base formation. Purer membrane preparation provided results showing predominant binding of gossypol to endoplasmic reticulum (ER) and mitochondria, followed to a lesser extent by peroxisomes and plasma membranes. Difference spectra of the gossypol-bound rat hepatic microsomal preparations and controls demonstrated a 3 nm shift from 413 to 410 nm caused by gossypol covalent-binding. Results of this study indicate that gossypol binds covalently to microsomal proteins. Its binding to membrane proteins may affect metabolism of sterols, steroids, or fatty acids.

Animals↗
PubMed1991

Gossypol pharmacokinetics in mid-lactation Brown Swiss dairy cows.

A bolus equivalent to 450 ppm (dosage based on average feed intake for lactating dairy cows of similar mass) of gossypol was administered orally to three Brown Swiss dairy cows in mid lactation daily for a 7-day treatment period. Blood samples were taken during a 2-day pretreatment period, the 7-day treatment period and a 6-day recovery period. The serum recovered from the cows was stored at -20 degrees C until analysis for extractable gossypol content. The highest concentration of gossypol (a mean of 0.53 microgram/ml serum) was attained in all the cows on day 6 of the treatment period, indicating that a steady-state condition had been reached before the end of the treatment period. The gossypol concentrations then gradually declined during the 6-day recovery period but never fell to the zero baseline. The cows exhibited terminal elimination half-lives of 67, 67.5 and 40 h. Gossypol elimination was best described by a bi-exponential decay curve in two cows and a mono-exponential decay curve in the remaining cow.

Absorption↗
PubMed1991

Zone-specific hepatotoxicity of gossypol in perfused rat liver.

Gossypol selectively damages the periportal region of lobules in perfused rat liver, while retrograde perfusion caused pericentral liver damage. Moreover, the addition of 0.4% bovine serum albumin(BSA) to the perfusate completely prevented the toxic effect of gossypol on hepatocytes, decreasing the absorption of gossypol by the liver. This study indicates that the damage caused by gossypol depends upon the direction of exposure and can be protected against by its binding to BSA.

Animals↗
PubMed1991

Oligomerization and transport of the envelope protein of Moloney murine leukemia virus-TB and of ts1, a neurovirulent temperature-sensitive mutant of MoMuLV-TB.

Ts1, a temperature-sensitive mutant of Moloney murine leukemia virus-TB (MoMuLV-TB), causes a progressive hindlimb paralytic disease in susceptible strains of mice. Previously, it has been shown that a single amino acid substitution, Val-25----Ile in gPr80env, is responsible for the temperature sensitivity, inefficient transport, and processing of gPr80env at the restrictive temperature and the neurovirulence of ts1. Since the neurovirulence of ts1 is associated with inefficient transport and processing of gPr80env and since in other systems involving viral envelope proteins it has been shown that correct folding and oligomerization of envelope monomers are required for efficient transport, we have investigated the ability of gPr80env derived from either wild-type MoMuLV-TB or ts1 to associate into oligomeric complexes. In these experiments, we establish that at both the restrictive and the nonrestrictive temperatures gPr80env molecules derived from MoMuLV-TB associate to form oligomeric complexes and these oligomers are most likely trimers. gPr80env molecules derived from ts1 also oligomerize at both temperatures; however, at the restrictive temperature, most of the molecules within the trimeric complexes remain as gPr80env and are not processed to gp70 and Prp15E. These results indicate that lack of oligomerization of gPr80env is not responsible for the transport defect of ts1. Therefore, by interacting specifically with critical sites within target cells, oligomers of mutant gPr80env rather than "tangles" of monomeric viral envelope proteins may be involved in the neurodegenerative disorder produced by ts1.

Animals↗
PubMed1991

Inhibition of rat embryo implantation in the gossypol-treated uterine horn.

We have developed a method to test the effect of gossypol on prevention of embryo implantation in the uterine horn. On the day of proestrus, gossypol (at a dose of 50, 100, 150, 200 and 500 mug per uterine horn was injected directly into the lumen of the right uterine horn. The left uterine horn was injected with 100 mul buffer. The rats were then mated with fertility proven males on the same day. The day of sperm-positive vaginal smear was designated as Day 0 of pregnancy. The number of implantation sites in both control and gossypol-treated horns was examined on Day 8 of pregnancy by laparotomy. The number of pups born was counted after parturition. At laparotomy, the percentages of pregnant animals with positive implantation sites in the gossypol-treated uterine horn (at a dose of 500, 200, 150, 100 and 50 mug per uterine horn) were 0, 0, 0, 10 and 44%, respectively. By contrast, implantation sites were present in 100% of the control horns of the same rats. The average numbers of total implantation sites in both horns vs the number of pups born to gossypol-treated animals using 500, 200, 150, 100, and 50 mug doses were 5.60 +/- 1.25 vs 4.00 +/- 1.00, 5.83 +/- 1.30 vs 4.70 +/- 1.10, 5.80 +/- 1.10 vs 5.50 +/- 1.20, 11.50 +/- 1.00 vs 9.50 +/- 1.50 and 11.67 +/- 1.20 vs 9.30 +/- 1.20, respectively. Gossypol metabolite completely inhibited embryo implantation when administered at 5.30 mug per uterine horn. The potency of the gossypol metabolite in preventing embryo implantation is estimated to be at least 28 times higher than the parent compound.

Journal Article↗
PubMed1991

Fertilizability and subsequent developmental ability of bovine oocytes matured in medium containing epidermal growth factor (EGF).

We have previously shown that epidermal growth factor (EGF) is capable of promoting maturation of bovine cumulus-oocyte complexes in chemically defined serum-free medium. In this study, fertilizability and subsequent developmental capacity of bovine oocytes matured in EGF-containing medium were evaluated. Fetal bovine serum (FBS, 10%) and EGF at 10 ng/ml in Dulbecco's modified Eagles medium with Ham's nutrient mixture F-12 (DME/F12) significantly increased the rate of formation of two pronuclei compared with the rate obtained from DME-F12 alone (P<0.05). Early embryonic development was assessed during 48 h in culture. Data were evaluated in terms of cleavage and four- to eight-cell formation. Oocytes matured in 10 ng/ml EGF showed significantly higher rates of cleavage (P<0.01) and four- to eight-cell formation than did oocytes matured in control medium (P<0.05). Bovine oocytes matured in the presence of EGF can be normally fertilized and can cleave and develop in vitro up to the eight-cell stage.

Journal Article↗
PubMed1991

Gossypolone suppresses progesterone synthesis in bovine luteal cells.

Gossypolone, a proposed major metabolite of gossypol, was synthesized and investigated for its effect on progesterone synthesis in cultured bovine luteal cells. Gossypolone inhibited human chorionic gonadotropin(hCG)-stimulated progesterone secretion, reduced substrate-enhanced conversions of 25-hydroxycholesterol to pregnenolone and of pregnenolone to progesterone in a dose-dependent fashion. These findings indicate that gossypolone inhibits not only 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) activity, as gossypol does, but also side-chain cleavage enzyme complex (cytochrome P450scc) activity. However, the two compounds appear to have a similar potency in inhibiting progesterone secretion. Both gossypolone and gossypol (8.5 microM) induced morphological changes in cellular organelles.

3-Hydroxysteroid Dehydrogenases↗
PubMed1991

Effects of progesterone and gossypol on monoamine oxidase activity in human term placental explant.

Human placental explant was cultured, using fresh full term placenta delivered by elective cesarean section (n = 10), and monoamine oxidase (MAO) activity was measured in the tissue by the spectrophotometric method. Placentae were obtained from patients without complications in pregnancy. Chorionic villi 2 g was incubated for 3 hr under the 95% air-5% CO2 humidified condition at 37 degrees C. When progesterone was added in the media (100-500 micrograms/ml), MAO activities significantly decreased, compared with the control. The gossypol (100 micrograms/ml) treated group showed no inhibitory or stimulatory effects on MAO activities, compared with the control. However, progesterone (100-500 micrograms/ml) and gossypol (100 micrograms/ml) treated group showed the same value of MAO activities, compared with the control. Those results indicate that gossypol might block progesterone action which is inhibitory against MAO activity. The mechanism of pharmacological function of gossypol was discussed.

Female↗
PubMed1991

Suppression of adrenocorticotropic hormone (ACTH)-induced corticosterone secretion in cultured rat adrenocortical cells by gossypol and gossypolone.

We have reported that gossypol, an antifertility agent, and gossypolone, a major metabolite of gossypol, inhibited steroidogenesis in bovine luteal cells in vitro. In the current study, the effects of these two compounds on steroidogenesis were examined in adrenocortical cells of young rats. ACTH-induced corticosterone secretion and intracellular adenosine monophosphate (cAMP) formation were significantly inhibited by gossypol at concentrations of 8.6 and 4.3 microM, respectively, and by gossypolone at concentrations of 8.6 and 4.3 microns, respectively. The present study demonstrated that both compounds inhibit ACTH-induced corticosterone synthesis and secretion in rat adrenocortical cell and this inhibition is, at least partially, attributed to the reduction of intracellular cAMP formation. Our data suggest that gossypol and its metabolite(s) probably affect steroidogenesis not only in gonads but also in adrenal glands by a common mean-reduction of intracellular cAMP.

Adrenal Cortex↗
PubMed1991

Detection of human papilloma virus (HPV) in laryngeal carcinoma tissue.

Using alpha-32P-dCTP labelled human papillomavirus type 16 DNA genome probe (cHPV 16 DNA, cloned and identified from a Chinese cervical invasive carcinoma), 3 HPV 16 genomic relative sequences were detected in 6 biopsies of laryngeal carcinoma. The results showed serious HPV infection in laryngeal carcinoma. This indicates that HPV infection may play an important pathogenetic role in cancer development.

Blotting, Southern↗
PubMed1991

Expression of macrophage colony-stimulating factor (M-CSF) in two Hodgkin's Reed-Sternberg (H-RS) cell lines, HDLM-1 and KM-H2, and in H-RS cells in tissues.

The authors studied the production of macrophage colony-stimulating factor (M-CSF) and the expression of its receptor (c-fms) in two Hodgkin's Reed-Sternberg (H-RS) cell lines, HDLM-1 and KM-H2 and in H-RS cells in tissues. We found that both types of H-RS cell can produce M-CSF, as was confirmed by the presence of M-CSF mRNA and protein in the cells and by the presence of macrophage colony-stimulating activity in conditioned medium. M-CSF was also expressed by H-RS cells in lymph nodes from patients with Hodgkin's disease. In cultures, KM-H2 cells appeared to produce a lesser amount of M-CSF than did HDLM-1 cells, as indicated by weaker staining with anti-M-CSF in the former cells. In KM-H2 cells, most of the M-CSF was located in the cytoplasm, and in HDLM-1 cells, in the Golgi apparatus and/or on the cell membrane. The two types of cultured H-RS cell either did not express c-fms at all, or expressed it only extremely weakly, perhaps because of the loss of dependence on specific growth factors during culture. The production of M-CSF by H-RS cells may contribute to the clinical and pathologic changes seen in patients with Hodgkin's disease, such as the increased abundance of histiocytes in tissues infiltrated by H-RS cells. Alternatively, the expression of both M-CSF and c-fms could confer a growth advantage to some H-RS cells in an autocrine fashion.

Animals↗
PubMed1991

Simultaneous ectopic pregnancy with intrauterine gestation after in vitro fertilization and embryo transfer.

A case of combined intrauterine and tubal ectopic pregnancy is described following in vitro fertilization and the transfer of two four-cell and one two-cell embryos. This phenomenon is known to be related to ovarian stimulation by gonadotropin therapy, and there is an increased risk with tubal disease. Techniques applied at the time of embryo transfer, the use of culture medium with 50% fetal cord serum to convey the embryos to the uterus, the catheterization method, and the position of the patient during transfer are presented. The risk of multiple pregnancies and combined intrauterine and ectopic gestations increases with increasing numbers of transfers and large volume of transfer medium. We would therefore recommend that after IVF-ET treatment in women with tubal disease, intensive care should be taken in the early follow-up period to rule out the possibility of ectopic pregnancy. In this case, a viable ongoing intrauterine pregnancy was confirmed after surgery for right ampullary ectopic pregnancy. And a 2925gm male in excellent condition was delivered by cesarean section without complications.

Adult↗
PubMed1990

Estrogen metabolism in primary kidney cell cultures from Syrian hamsters.

Estrogen metabolism was evaluated in freshly isolated kidney and liver microsomes and in primary kidney cell cultures from Syrian hamsters, a potential experimental model for examining the possible role(s) of estrogens in tumor initiation and development. Initial velocity studies of the conversion of estradiol to 2-hydroxyestradiol, as determined by the 3H2O release assay with the substrate [2-3H]estradiol, resulted in similar apparent Kms of estrogen 2-hydroxylase of 2.85 and 6.25 microM for liver and renal microsomes, respectively. The apparent Vmax for freshly prepared liver microsomes was 0.13 nmol.mg-1.min-1, while that for renal microsomes was 0.040 nmol.mg-1.min-1. Evaluation of estrogen metabolism was also performed in primary cell cultures of hamster kidney cells, consisting of 75% epithelial cells. [6,7-3H]Estradiol (10 microM) was incubated for 0, 24 and 48 h in primary kidney cell cultures, and the organic soluble metabolites analyzed by reverse-phase HPLC. The cultures from untreated, castrated hamsters metabolize [3H]estradiol to yield small quantities of estrone and significant amounts of polar metabolites, while no catechol estrogens were isolated. Estrogen metabolism by diethylstilbestrol-treated (DES-treated) hamster kidney cell cultures also provided small quantities of estrone and no evidence of catechol estrogens. Additionally, larger amounts of additional polar metabolites were isolated in the cultures from DES-treated hamsters. Finally, levels of estrogen 2-hydroxylase were detected in these cultures using the 3H2O release assay. Thus, the short-term primary kidney cell cultures from the Syrian hamster are capable of metabolizing estrogens. Furthermore, the enzymatic processes appear to be available for the conversion of any catechol estrogens formed into more polar metabolites. These investigations in intact cells, capable of performing all biochemical processes, complement both in vivo and subcellular biochemical studies and may aid in elucidating the roles of estrogens and estrogen metabolism in the initiation and development of estrogen-induced, estrogen-dependent kidney tumors in the Syrian hamster.

Animals↗
PubMed1990

Inhibitory effect of gossypol on steroidogenic pathways in cultured bovine luteal cells.

Gossypol inhibits the reproductive system and steroidogenesis in both sexes. The present study investigated some possible sites subsequent to cAMP formation at which gossypol may inhibit progesterone biosynthesis. Bovine luteal cells were cultured with dibutyryl cAMP (dbcAMP), 25-OH cholesterol, or pregnenolone in the presence or absence of gossypol. Gossypol, at 17-34 microM, inhibited dbcAMP-induced progesterone secretion. Gossypol significantly inhibited the conversions of exogenous 25-OH cholesterol and pregnenolone to progesterone. However, the conversion of 25-OH cholesterol to pregnenolone was not significantly inhibited by gossypol at low doses (less than or equal to 34 microM). These results suggest that gossypol inhibits progesterone synthesis in bovine luteal cells by suppressing steroidogenic enzyme activity.

Animals↗