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Biomedical subjects

Y C Lin

Publications and source records attributed to Y C Lin.

At least 181 records · Page 10Linked to original sources

Prolonged stabilization of progressive endometrial stromal sarcoma with prolonged oral etoposide therapy.

We report the case of a patient who has a 23-year history of endometrial stromal sarcoma (ESS). She initially underwent tumor-reductive surgery followed by adjuvant radiotherapy. The pelvic tumor recurred nearly 8 years later, obstructing the ureter and directly invading the bladder. It propagated into the vena cava as a thrombus and finally spread into the right heart chambers, leading to cardiac failure 13 years after the recurrence. The patient was treated with hormonal therapy, multiple resections of the pelvic tumor, chemoembolization, and systemic chemotherapy with doxorubicin and cyclophosphamide. She developed recurrent intractable symptoms and was started on prolonged oral etoposide therapy, which stabilized the size of the pelvic tumor and relieved her symptoms for 3 years. Her quality of life has markedly improved without significant morbidity. We review the options for treating recurrent ESS and suggest that use of prolonged oral etoposide therapy warrants further study in this setting.

Administration, Oral↗

Antiproliferative activity of gossypol and gossypolone on human breast cancer cells.

Gossypol is a polyphenolic aldehyde occurring naturally in cottonseed that produces antisteroidogenic activity in vivo, has been extensively investigated as a male contraceptive agent, and has demonstrated anticancer activity. Gossypolone, the major metabolite of gossypol, also prossesses antisteroidogenic activity but has not been examined for its anticancer properties. The objectives of these investigations are to compare the effects of gossypolone with those of gossypol on cell proliferation of hormone-dependent and hormone-independent human breast carcinoma cells, i.e., MCF-7, MCF-7 Adr and MDA-MB-231 cells. Gossypol and gossypolone were examined at concentrations up to 10 microM, and cellular DNA synthesis was monitored by 3H-thymidine incorporation. Gossypol and gossypolone produced dose-dependent suppression of DNA synthesis in all of the human breast cell lines examined. Gossypol produced potent antiproliferative activity in MCF-7 cells at doses as low as 30 nM. Co-incubation of MCF-7 cells with gossypol (5 microM) and estradiol (10 nM) did not alter the effects of gossypl. Treatment of human breast cancer cells with 2.5 microM of gossypol resulted in alterations in cell shape and attachment to the surface of the culture dishes. At gossypol doses of 10 microM, pericytoplasmic globuation and cytoplasmic swelling were observed in the majority of breast cancer cells. These changes in cellular morphology indicate a loss of ability of the cells to maintain normal cell membrane permeability, resulting in subsequent disorganization and loss of cytoplasmic organelles. Gossypolone is less potent than gossypol in producing these effects in the human breast cancer cell lines, whereas it possesses equipotent antisteroidogenic and antireproductive activities with gossypol. These investigations suggest that gossypol and gossypol analogs may have therapeutic potential for human breast cancer.

Antineoplastic Agents↗

Coumarins and anti-platelet aggregation constituents from Zanthoxylum schinifolium.

Six new coumarins, schinicoumarin, acetoxyaurapten, epoxycollinin, schininallylol, schinilenol and schinindiol, along with seven known coumarins, aurapten, collinin, epoxyaurapten, hydrangetin, umbelliferone, acetoxycollinin and aesculetin dimethyl ether, three known alkaloids, norchelerythrine, dictamnine and skimmianine, and two triterpenoids, beta-amyrin and friedelin, were isolated and characterized from the chloroform-soluble part of the bark of Zanthoxylum schinifolium. The structures of these compounds were elucidated by spectral analyses. Separation accompanied by bioassay-guided fractionation resulted in the isolation of seven compounds with strong inhibitory activity on platelet aggregation in vitro. These are schinicoumarin, acetoxyaurapten, schininallylol, aurapten, collinin, (-)-acetoxycollinin and dictamnine.

Animals↗

Estrogen metabolism in microsomal, cell, and tissue preparations of kidney and liver from Syrian hamsters.

The estrogen-treated golden Syrian hamster has been used as an experimental model for estrogen-induced and estrogen-dependent cancers, but pathways to neoplastic transformation remain unknown in this animal. Metabolism of estrogens to activated or reactive compounds, followed by subsequent oxidative damage to the target tissue, remains a potential step in the tumorigenic process. In this study, the extent of estrogen metabolism is compared in three different in vitro preparations from untreated and estrogen-treated Syrian hamsters, primary kidney cell cultures, microsomal preparations, and freshly prepared tissue kidney slices. In primary kidney cell cultures, the amount of catechol estrogens decreased upon increasing estrogen (DES) treatment period, and completely disappeared after about 6 months treatment. This decrease is not a result of formation of less amounts of catechol estrogens, but rather reflects the presence of the enzyme systems to further metabolize any formed catechol estrogens, since the amount of catechol estrogens formed, as detected by 3H2O release, is unchanged. The polar metabolites a, b and c increased with estrogen treatment, and metabolite c appeared only after DES treatment. The appearance of polar metabolite c only in kidney preparations from DES-treated animals implies that it may serve as a marker of cellular transformation. Estriol and estrone were detected, but were not affected by DES treatment, while no methoxyestrogens were isolated. Studies of estradiol metabolism in microsomal preparations showed a very low rate of metabolism, compared to the primary kidney cell cultures. In contrast, estrogen metabolism was extensive in kidney slices from untreated hamsters, with only approx. 30% of the substrate estradiol remaining unmetabolized after 6 h of incubation. While no catechol estrogens were detected, a small quantity of estriol, and a large amount of estrone and methoxyestrogens were isolated. The polar metabolite a was the main polar metabolite detected, with very little of metabolite b and no metabolite c. In kidney slices from 4 month DES-treated hamsters, a much higher amount of polar metabolites was detected, and metabolite c appeared after 6 h incubation. Mass spectrometric analysis and HPLC data of metabolite c indicate that this metabolite is 15 alpha-hydroxyesteradiol. This metabolite may serve as a biomarker for changes occurring in the hamster kidney cells under continuous estrogen exposure. Finally, formation of water soluble conjugates was demonstrated in both kidney slices and liver slices from Syrian hamsters, with glucuronide, sulfate and thioether conjugates of estrone and estradiol and glucuronides of catechol estrogens detected.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Regulation of cumulus cell steroidogenesis by the porcine oocyte and preliminary characterization of oocyte-produced factor(s).

This study was designed to investigate whether porcine oocytes produce a factor(s) that influences cumulus and mural granulosa cell steroid production and to characterize the biochemical nature and mode of action of a such factor(s). Porcine cumulus-oocyte complexes (COC) were collected from 2-5 mm follicles and cultured either intact or after oocytectomy for 48 h. Steroid levels were then measured in the culture media. Conditioned media, obtained by culturing denuded oocytes for 48 h, were subjected to heat treatment of charcoal extraction and utilized to culture intact and oocytectomized COC. FSH-stimulated progesterone, 20 alpha-OH-progesterone, and estradiol were significantly higher in oocytectomized vs. intact COC cultures. Denuded oocytes cultured with granulosa cells significantly inhibited progesterone production compared to control. Also, media conditioned with different numbers of denuded oocytes (0 to 300) significantly inhibited progesterone production by oocytectomized COC in a manner dependent on oocyte number. Charcoal extraction, but not heat treatment, significantly removed the inhibitory effect of the conditioned media on progesterone production by oocytectomized COC. Increased progesterone production by oocytectomized COC was not accompanied by a similar increase in cAMP formation. Heptanol, a gap junction blocker, did not alter progesterone production by intact COC. In conclusion, porcine oocytes secrete a factor(s) that inhibits cumulus and mural granulosa cell steroidogenesis. This factor(s) is heat stable but extractable by charcoal. The factor(s) appears not to be transferred to somatic cells via gap junctions, and its effect is downstream of cAMP formation.

Animals↗

Microangiopathic hemolytic anemia as an initial presentation of metastatic cancer of unknown primary origin.

Microangiopathic hemolytic anemia (MAHA) is a well-documented but rare complication of disseminated cancer; it usually occurs in the late or terminal stage of cancer. We describe a case of metastatic carcinoma of unknown origin in which MAHA was the initial presentation. A 36-year-old woman came to our hospital with lower back pain and progressive exertional dyspnea for 8 weeks. Hemolytic anemia, thrombocytopenia, and leukoerythroblastosis were found on admission. The peripheral blood smear revealed polychromasia, poikilocytosis, and many schistocytes. Bone marrow biopsy disclosed metastatic carcinoma. After careful workup, we failed to find the primary site of cancer. The anemia and thrombocytopenia responded dramatically to combination chemotherapy with 5-fluorouracil, mitomycin C, and cisplatin. This case indicates that metastatic carcinoma should be included in the differential diagnosis in previously healthy patients with MAHA.

Adenocarcinoma↗

Cardiovascular deconditioning occurs during a 7-day saturation dive at 31 ATA.

Cardiovascular deconditioning (CD) has been reported to occur within 24-48 h of exposure to 4, 11, or 31 ATA environment and following decompression to sea level pressure. The CD was indicated by orthostatic intolerance, exaggerated cardiovascular responses to a passive tilt, an elevated resting heart rate and a reduced stroke volume postdive. In this dive, one of the New Seatopia series, we used a non-syncope criterion, the cardiovascular index of deconditioning (CID; Bungo MW, Johnson PJ Jr. Aviat Space Environ Med 1983; 54:1001), to evaluate CD in 3 male subjects. The CID sums the changes in heart rate and blood pressure in response to orthostatic stress. An elevated CID indicates CD. We used a passive 70 degrees head up tilt as the orthostatic stress. The CID was measured before and after a bout of underwater exercise at predive, during the early, mid, and late exposure of the 7-d 31 ATA, and after the dive. The CID and circulatory responses to tilt were similar before and after the exercise. The CID increased (p < 0.05) from the predive value of 20 +/- 1.6 to 25 +/- 0.9 on the 2nd day, to 25 +/- 0.8 on the 4th day at 31 ATA, indicating the presence of CD at the early and mid periods of hyperbaric exposure. However, CID was indifferent (18 +/- 0.6) from the predive on the 7th day at 31 ATA. The increased CID corresponded to decreases in plasma volume during the early and mid periods of 31 ATA exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Observation of cardiac function, hemorheology and lingual microcirculation of leukemic patients].

The cardiac function, hemorheology and the lingual microcirculation of the 62 leukemic patients were investigated. The results showed that their left cardiac function was markedly damaged, and the blood specific viscosity and hematocrit lowered, the time of RBC electrophoresis extended, the ESR and the K value of ESR equation was increased, which suggested the blood agglutination was enhanced. The lingual microcirculation obviously displayed reducing the number of papilla fungiformis, of intrapapillar plexus of microvessel as well as vessel loops, it also revealed the increasing of the abnormal form of microvessel and of the dilating vessel loops. The colour of the blood flow showed pink and dark red, the condition around vessel loops showed exudation and bleeding in several cases.

Adolescent↗

Diurnal renal responses in man to water loading at sea level and 31 atm abs.

The hyperbaric environment causes a sustained diuresis accompanied by normal water intake and a decrease in insensible water loss. The maintained water intake may be necessary for the maintenance of water balance because of a reduced ability of the kidney to retain water, or may be causal in the diuresis. This problem was studied in four male subjects. Each ingested 1 liter of water (15 degrees C) at 0800 and 2000 h on different days, at 1 atm abs during a predive control, at 31 atm abs, and at 1 atm abs during the postdive control period. Urine was collected 30 min before and 3 h after the drink. Plasma vasopressin (VP) showed a circadian rhythm only at 1 atm abs, higher during the daytime. Because of this, and slightly lower VP levels at hyperbaria, a decrease in VP in response to the water load was significantly detectable only at 1 atm abs during the daytime. At 60 min after all water loads, there were no differences in plasma VP or plasma or urinary osmolality. Variability in the length of time of similarly reduced urine osmolality and increased free water excretion accounted for the increased urine flow during day compared to night (P < 0.05) at 120 and 150 min after the water load. The ability to excrete a water load both day (free water clear-ance, P < 0.05 at 60 min post-drink) and night (free water clearance, P < 0.05 at 60, 90, and 120 min post-drink) at 31 atm abs was enhanced. It is concluded that maintained water intake at hyperbaria is necessary to maintain water balance because there is a reduced ability of the body through renal mechanisms to retain a water load.

Adult↗

Presence of antitumor activities in the milk collected from gossypol-treated dairy cows.

Two human breast carcinoma cell lines (MCF-7, MCF-7 Adr) and a rat esophageal cancer cell line (RE-B2T) were used to evaluate the antiproliferative potential of gossypol (GP)-containing milk (GP-Milk), which was collected from Brown Swiss dairy cows treated daily with federally allowable 450 ppm of GP for 6 days. Treatment of the cultured cancer cells with GP-Milk for 24 h significantly inhibited the rates of 3H-thymidine incorporation during the ensuing 3-h period in all three tumorigenic cell lines. The inhibitory effects of GP-Milk occurred in a dose-dependent manner in all cases, but the calculated ED50 varied with cell lines. ED50 for GP-Milk was estimated at 10% for wild-type MCF-7 human breast cancer cells, 15% for multidrug-resistant MCF-7 Adr human breast cancer cells and 50% for RE-B2T rat esophageal carcinoma cells. The potential of GP-Milk as a dietary supplement for the prevention and/or treatment of human breast cancer is discussed in this paper.

Animals↗

Effects of transforming growth factors and activin-A on in vitro porcine oocyte maturation.

Growth factors are known to regulate ovarian function. In the present study, effects of these growth factors, TGF-alpha, TGF-beta, and activin-A were tested on spontaneous porcine oocyte maturation. Cumulus-oocyte complexes (COC) were cultured in the presence of TGF-alpha, TGF-beta, and activin-A for 48 hr. Stages of meiotic maturation were assessed by staining with acetic orcein. Among these factors, only TGF-alpha significantly enhanced the maturation rate, whereas TGF-beta suppressed the spontaneous maturation rate. The site of action of TGF-alpha on COC and the interaction between TGF-alpha and EGF receptor was also examined. Denuded oocytes, alone or in coculture with cumulus cells, were cultured in the presence of TGF-alpha for 48 hr. TGF-alpha did not have any significant effect on denuded oocyte maturation. Heptanol was employed to investigate the role of gap junctions on TGF-alpha-induced oocyte maturation in COC. Although heptanol did not have any significant effect in the control medium, heptanol reversed the stimulatory effect of TGF-alpha on porcine oocyte maturation. TGF-alpha was able to displace 125I-EGF binding on COC. In conclusion, TGF-alpha enhances the spontaneous maturation of porcine oocytes by generating positive signal(s) in cumulus cells that are transferred to the oocyte via gap junctions. TGF-alpha shares the same receptor with EGF on porcine COC. TGF-beta, in contrast, inhibits porcine oocyte maturation.

Activins↗

Inhibition of in vitro fertilization and early embryonic development in hamsters by gossypol.

We have previously reported an inhibitory effect of gossypol and its metabolite on bovine and mouse early embryonic development. In the present study, eggs were collected from oviducts of superovulated hamsters. Epididymal sperm were used for in vitro fertilization (IVF). Gossypol at 5, 10, and 30 micrograms/ml significantly inhibited the formation of 2 pronuclei by 45, 65 and 95%, respectively. On the first day of pregnancy, hamsters were given an intrauterine treatment of 200 micrograms of gossypol in 100 microliters of corn oil per uterine horn. On day 3, embryos from controls were in morula (65%) and early morula (17%) stages, while less than 2% of embryos from the gossypol-treated hamsters were in the morula stage. The numbers of embryo implantation sites on day 8 and pups in controls (14 +/- 2.0 and 12 +/- 1.5, respectively) were significantly higher than those in the gossypol-treated hamsters (8.5 +/- 2.0 and 4.0 +/- 1.5, respectively). Our results suggest that gossypol is able to affect fertilization, embryonic development, embryo implantation, and the number of pups in hamsters through a not-yet-defined mechanism.

Animals↗

Gossypol inhibits aromatase activity in cultured porcine granulosa cells.

The present study investigated whether gossypol inhibited aromatase activity in cultured porcine granulosa cells. Aromatase activity was assayed by measuring (3)H-H(2)O released from [1beta-(3)H]-androstenedione. First, immature porcine granulosa cells were cultured with various doses of follicle stimulating hormone (FSH, 1 to 1000 ng/ml) for 1 to 5 d to determine optimal culture conditions for aromatase activity assay. Second, porcine granulosa cells were cultured with or without FSH in the presence or absence of gossypol. Gossypol, at 4 muM, significantly inhibited FSH-induced aromatase activity while showing no effect on basal aromatase activity. Gossypol did not inhibit cell proliferation during cell culture. These results suggest that gossypol inhibits aromatase activity by interfering with FSH induction of aromatase in cultured porcine granulosa cells.

Journal Article↗

A simple method for obtaining highly viable virus from culture supernatant.

Traditionally density-gradient methods are used to purify viruses. However, these procedures are not only time consuming and cumbersome, recovery of viable viruses are often quite low. In this report, a single-step concentration technique was used to concentrate a mutant of Moloney murine leukemia virus (ts1) virus from culture supernatants by ultrafiltration. A special ultrafiltration unit with a 100,000 mol wt cut-off was able to concentrate viruses about 30-fold without losing any infectivity. In comparison, traditional sucrose density gradient purified viruses lost a significant portion of their infectivity. This technique could be used for concentrating other viruses for many useful purposes where more viable viruses are needed, e.g., study of virus-cell binding.

Cell Line↗

Characterization of the stimulatory actions of thymic factor(s) on basal and gonadotropin-induced steroidogenesis in cultured rat granulosa cells.

Recently, there have been numerous reports that demonstrate the importance of the thymus gland in reproductive physiology. Previously, we have reported that thymic factors (TFs) which are present in thymic cell culture-conditioned medium (TCM) could stimulate basal progesterone and estradiol production from cultured rat granulosa cells. The current study attempts to characterize the stimulatory actions of TFs on both basal and FSH induced steroidogenesis. Thymic epithelial cells from immature female rats were isolated and used for production of TCM. Granulosa cells were obtained from immature diethylstilbestrol (DES)-treated rats. TFs stimulated both basal and FSH-induced progesterone secretions 80 and 17 times, respectively, as compared to the control media. The effects of TFs on basal and FSH-induced 20 alpha-hydroxyprogesterone secretion were comparable to those on progesterone production (40x and 10x, respectively). In addition, TCM stimulated basal and FSH-induced estradiol secretion approximately 4 and 2.5 times, respectively, compared to control. Stimulation of aromatase enzyme activity followed a similar trend as estradiol secretion, and TCM stimulated basal and FSH-stimulated aromatase enzyme activity approximately 15 and 3 times, respectively compared to control. Thus, these results indicate that the observed increases in progesterone and estradiol secretions in TCM-treated rat granulosa cells are likely to be due to elevated activities of specific steroidogenic enzymes. Measurements of total cell protein and DNA synthesis indicate that enhanced steroidogenesis in TCM-treated cells is not due to increased cell growth and/or proliferation. Rather, the enhanced steroidogenesis is probably due to an increased steroid biosynthetic capability of the cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Application of conservation principle in estimating body volume in rats.

Obesity is a risk factor in diving and aviation during acute reduction of pressure, because N2 is five times more soluble in fat than in water. In addition to concerns of decompression applications, body fat content (BFC) bears importance in the disposition of drugs, the evaluation of dietary regimens and exercise programs, and in long-term health status. Most of the currently available methods for quantifying BFC are impractical for small animals. We devised a method that does not require the cooperation of the animal. Our method uses a simple gas-dilution technique to measure the body volume. The body density was determined as the ratio of body weight (g) to body volume (ml). After the whole body density was determined, the fraction of body fat was calculated according to established formulas. Calibration with aluminum blocks showed a high correlation (r = 0.99) between measured volumes and the known block volumes. Furthermore, comparing body volumes of shaved and unshaved rats showed that the volume of air between hairs did not affect the measurement of body volume with the dilution method. In four groups, each consisting of 10 male Wistar rats [body wt 81 +/- 1 (SE), 152 +/- 3,297 +/- 5, and 496 +/- 4 g], BFC was 7.0 +/- 2.8, 14.6 +/- 1.9, 22.0 +/- 1.8, and 32.3 +/- 1.3%, respectively. These values compared favorably with chemically determined BFC values for rats in the literature. Our results suggest that the gas-dilution technique is a feasible and simple method for the determination of BFC in small animals.

Adipose Tissue↗

Monoamine oxidase activity in rat organs during pregnancy.

To elucidate the involvement of MAO activity in rat pregnancy, female rats exhibiting at least 3 consecutive 4-day estrous cycles were used. The day of sperm-positive smears was designated as day 0 of pregnancy. The rats were sacrificed on day 2 of diestrus (diestrus-2) and days 7, 14 and 21 of gestation. The organs were collected and weighted, and mitochondrial fractions were prepared for MAO analysis with kynuramine dihydrobromide as substrate. Specific activity (pmol/mg of protein/min) in the ovary is significantly lower in rats on diestrus-2 (792 +/- 127) (mean +/- S.D.) than on day 14 (1,038 +/- 140) and day 21 (1,580 +/- 61) of pregnancy. However, the levels of MAO activity in the uterus of rats on diestrus-2 (899 +/- 266) is higher than on day 21 (570 +/- 80) of pregnancy. The MAO activity in the placenta on day 21 (644 +/- 82) was higher than day 14 (356 +/- 88) of pregnancy. Total MAO activity per organ (nmol/min) of ovary on day 21 (27.2 +/- 5.2) is higher than on diestrus-2 (8.7 +/- 3.0) and on day 14 (14.2 +/- 3.6). Our results suggest that MAO activity in rat reproductive organs such as uterus, ovary, and placenta might fluctuate significantly near term, in correlation with steroid levels, tissue catecholamine contents and so on, in order to maintain pregnancy.

Animals↗