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Biomedical subjects

Y C Lin

Publications and source records attributed to Y C Lin.

At least 217 records · Page 12Linked to original sources

Stress-relaxation of fibroblasts in collagen matrices triggers ectocytosis of plasma membrane vesicles containing actin, annexins II and VI, and beta 1 integrin receptors.

To learn about the effects of tension on fibroblast function, we have been studying initial cellular responses to stress-relaxation. Human foreskin fibroblasts were cultured in anchored collagen matrices for 2 days, during which time mechanical stress developed. Subsequently, the matrices were dislodged; thereby allowing stress to dissipate. Within 5 min after initiating stress-relaxation, fibroblasts retracted their pseudopodia. At this time, we observed the disappearance of cellular stress fibers and the formation of actin clusters along the cell margins. The actin was found to be located inside 200 nm diameter vesicles that were budding from the cell surface. Vesicles isolated from the matrix after stress-relaxation contained prominent 24 kDa, 36 kDa (doublet), 45 kDa, and 135 kDa polypeptides. The 45 kDa polypeptide was the major component in the Triton-insoluble vesicle fraction and appeared to be actin. The 36 kDa (doublet) polypeptide, which was found predominantly in the Triton-soluble vesicle fraction, was identified as annexin II. Vesicles also contained annexin VI and beta 1 integrin receptors but not tubulin, vimentin, vinculin or annexin I. The results suggest that stress-relaxation of fibroblasts induces a novel ectocytotic process involving transient budding of intact, plasma membrane vesicles from the cell cortex. On the basis of their morphological and biochemical features, these vesicles may be analogous to the 'matrix vesicles' released by chondrocytes and could play a role in extracellular matrix remodeling after wound contraction.

Actins↗

[Protective action of blumeatin against experimental liver injuries].

Blumeatin (Blu, 5,3',5'-trihydroxy-7-methoxy-dihydro-flavone) was first isolated from Blumea balsamifera DC by Department of Chemistry, Sunyatsen University of China. Blu ip inhibited the increase of serum alanine aminotransferase (AAT) and liver triglyceride and increased serum triglyceride, beta-lipoprotein, and liver glycogen content in CCl4-intoxicated rats. Histological lesions of liver were less severe than those of hepatic injury control. Blu ip 0.65 and 3.25 mg.kg-1 inhibited the increase of serum AAT and hepatic TG in thioacetamide (TAA)-intoxicated mice. Blu ip shortened the pentobarbital sleeping time in CCl4-intoxicated mice. It suggested that Blu could protect liver against injury induced by CCl4 and TAA.

Alanine Transaminase↗

Effect of gossypol on 5 alpha-reductase and 3 alpha-hydroxysteroid dehydrogenase activities in adult rat testes.

It has been reported that little to no 5 alpha-reductase can be detected in adult rat testes when progesterone is used as substrate. The 5 alpha-reductase activity in 4-month-old rats and the inhibitory action of gossypol on steroidobiosynthesis were studied. Testicular sections (10 microns thickness) were incubated at 30.5 degrees C in the presence of NADPH with 3H-testosterone and cold testosterone as substrates (9 microM total), and with or without gossypol as the test sample and control, respectively. Endogenous testosterone level was evaluated by radioimmunoassay. Reverse phase high performance liquid chromatography (HPLC) was used to separate the substrate and products. Components of interest were collected and their recovery monitored. At 200 microM concentration, gossypol significantly decreased dihydrotestosterone (DHT) formation by 21% when compared to that of control (0.6 pm/mg protein/min), and decreased 5 alpha-androstane-3 alpha,17 beta-diol formation by 35% vs control (2 pm/mg protein/min). In the current study, gossypol was found to have inhibitory effects of noncompetitive nature on 5 alpha-reductase, which catalyzes the conversion of testosterone to DHT, and on 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD), which interconverts DHT and dihydroandrostanediol.

3-Hydroxysteroid Dehydrogenases↗

Effective response evoked by microstimulation of thalamus nuclei in patients with tremor.

459 microstimulations were done in 10 patients with tremor. The motor evoked response with reduction tremor drive was observed at 38 sites, of which 30 (79%) were noted in ventrointermedialis (vim) nuclei, and 5 (13.2%) in ventrocaudalis (vc) nuclei, 2 in ventroralis posterior (vop) nuclei, 1 in dorsal thalamus (dth). No increased tremor drive response was noted in all the sites. Paresthesia was the most common response (47.1%). Except pain at 1 site in vc nuclei, warm/cold and vertigo were noted in vop, vim, vc nuclei. No responses accounted for 43.8%.

Electric Stimulation↗

Antiproliferative and antimetastatic effects of gossypol on Dunning prostate cell-bearing Copenhagen rats.

Gossypol, a polyphenolic aldehyde naturally present in cottonseed, has long been recognized as a male contraceptive and recently as a potential anticancer agent. Our study used a rodent model to evaluate gossypol's potential for the treatment of human prostatic carcinoma. Two-month-old Copenhagen male rats received subcutaneous implants of a subpassage of MAT-LyLu prostatic cancer line, a highly metastatic, androgen-independent Dunning prostate tumor subline that specifically metastasizes to lymph nodes and lungs of recipients. After 2 weeks of gossypol treatment (0 or 12.5 mg/kg B.W./day S.C.) initiated immediately after transplantation, the rats were sacrificed and evaluated for prostate tumor growth and metastasis. Testosterone and gossypol levels in tumor tissue and various reproductive organs and serum potassium level were measured by radioimmunoassay (RIA), high pressure liquid chromatography (HPLC) and atomic emission spectroscopy (AES), respectively. Gossypol-treated rats exhibited weight reductions in developed MAT-LyLu prostate tumor mass and prostate of 24% (p < 0.05) and 31% (p < 0.05), respectively; whereas testicular and epididymal weights were not significantly affected. Few metastases (20%) were observed in either lymph nodes or lungs of gossypol-treated recipients. The control rats, however, had a much higher rate of lung (60%) and lymph node metastasis (40%). Testicular testosterone levels, as measured by RIA, were significantly lower in gossypol-treated rats than in controls (p < 0.05), but serum testosterone levels were not different. Extractable gossypol content in the prostate tumor, as measured by HPLC, reached 19.67 ng/gm and was 1.28 times higher than in liver, 1.98 times higher than in testes, but was 3.3% of that in prostate. Moreover, serum had the highest gossypol content (10.7 micrograms/ml). Serum potassium levels, as measured by AES, were significantly higher in gossypol-treated individuals than controls (p < 0.05). Our results indicate for the first time that gossypol has antiproliferative and antimetastatic effects on MAT-LyLu prostate cancer cells and can be explored as a potential therapeutic agent for androgen-independent human prostatic carcinoma.

Androgens↗

Regulation of transcription of the germ-line Ig alpha constant region gene by an ATF element and by novel transforming growth factor-beta 1-responsive elements.

Inasmuch as transcription of unrearranged, or germ-line, Ig CH genes appears to direct switch recombination, understanding the regulation of this transcription is essential for understanding the regulation of class switching. Transforming growth factor-beta 1 (TGF-beta 1) induces germ-line alpha transcripts and increases class switching to IgA in the I.29 mu B lymphoma and in Peyer's patch and splenic B cells. It has been previously demonstrated that induction of germ-line alpha transcripts by TGF-beta occurs at the transcriptional level in I.29 mu cells. We now demonstrate that the DNA segment located 5' to the initiation sites of germ-line alpha RNA drives expression of a luciferase reporter gene construct in transient transfection experiments. Full constitutive expression requires no more than 106 bp of the 5' flanking segment. By creating a series of deletion and substitution mutations, we have demonstrated that an ATF/CRE site residing within this region is very important for constitutive expression of the germ-line alpha promoter, but mutation of this motif does not diminish TGF-beta induction. Inducibility by TGF-beta requires additional sequences residing between -128 to -106 relative to the first RNA initiation site. Two copies of a tandemly repeated sequence 5' CA-CAG(G)CCAGAC 3' (termed Ig alpha TGF-beta-RE) are located in the region from -127 to -105. An oligonucleotide containing multimers of these repeats confers TGF-beta inducibility to a heterologous promoter. An additional copy of the TGF-beta-RE was identified at -41/-30 and its deletion reduces the TGF-beta response. Thus, we conclude that tandem repeats of a novel TGF-beta-RE are the positive regulatory element for the TGF-beta response. Our study provides further evidence that TGF-beta directs class switching to IgA through induction of transcription of the germ-line C alpha gene and demonstrates that TGF-beta can activate the promoter for the germ-line alpha gene.

Activating Transcription Factors↗

Simultaneous ectopic pregnancy with intra-uterine gestation after in vitro fertilization and embryo transfer.

A case of combined intra-uterine 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 intra-uterine and ectopic gestations increases with 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 intra-uterine pregnancy was confirmed after surgery for right ampullary ectopic pregnancy. And a 2,925 g male in excellent condition was delivered by Cesarean section without complications.

Adult↗

Transfer of 3H-gossypol to neonatal rats via milk of nursing dams.

Gossypol is a naturally occurring toxin with potent antifertility action in both males and females. Transfer of gossypol via milk from lactating mother to neonates has not been documented. One theory for the lack of such a finding is that gossypol, once tightly bound to milk proteins, is not extractable by conventional extraction methods for HPLC analysis. This study was designed to examine the possibility and dynamics of transmammary transfer of radioactively-labelled gossypol to neonates through nursing. Nursing rats were dosed with fifty microCi of 3H-gossypol in 0.5 ml of dimethyl sulfoxide via oral intubation on Day 10 post-partum. Six hours after treatment, significant amounts of 3H-gossypol were detected in the coagulated milk collected from the stomachs of the neonates as well as in the blood, liver, lung, spleen and a number of other tissues of these pups. While most neonatal tissues showed a steady decline in 3H-gossypol retention over time regardless of neonatal gender, adrenal glands and gonads preferentially accumulated 3H-gossypol in a time- and sex-dependent manner during the 24-hour sampling period. The results demonstrate that 3H-gossypol is transferred via milk from the nursing dams to their neonates. Thus, the gossypol content of milk presents a conceivable threat to neonatal health, especially to the normal function of steroidogenic organs.

Animals↗

Stimulatory effect of thymic factor(s) on steroidogenesis in cultured rat granulosa cells.

Thymic cells from immature female rats were isolated and used for production of thymic cell culture conditioned medium (TCM). Granulosa cells were obtained from immature diethylstilbestrol (DES)-treated rats. TCM stimulated basal progesterone and estradiol secretion from the granulosa cells in a dose and time dependent manner. Maximal stimulation of progesterone production occurred at 48 hours of incubation, during which period TCM caused approximately 5 times more progesterone secretion than heart cell conditioned medium (HCM) or mock extract (ME). The maximum progesterone secretion by granulosa cells occurred when they were exposed to 48% TCM causing 7 times more progesterone secretion than controls. Under the same maximum stimulatory conditions, however, TCM only approximately doubled estradiol secretion compared to concentrations secreted in the presence of HCM or ME. Thus, the effect of TCM on progesterone secretion was more prominent than its effect on estradiol secretion. The stimulatory action of TCM was not mimicked by HCM, thymosin-alpha 1 or thymulin. Furthermore, the stimulatory action of TCM on steroidogenesis did not appear to be mediated by the cAMP system. The stimulatory factor(s) in TCM were heat, acid and acetone labile, but could not be sedimented by activated charcoal. Thus, the present study demonstrates that the secretory product(s) of thymic epithelial cells can stimulate steroidogenesis in cultured rat granulosa cells. Our data imply that thymic factor(s) may have a direct effect on ovarian function.

Acetone↗

Binding of 3H-gossypol in organelles of cultured bovine luteal cells.

Gossypol is an antifertility agent which inhibits steroidogenesis in both sexes. The present study investigated the binding of gossypol in organelles of cultured bovine luteal cell to elucidate its inhibitory site of action in steroid biosynthesis. Cultured bovine luteal cells were incubated with 3H-gossypol (4.3 or 2.15 microM) for 3 hours. At the end of treatment, cultured bovine luteal cells were harvested, homogenized and centrifuged for organelle preparation. The radioactivity of gossypol was measured in each subcellular fraction. The cell membrane fraction has the highest binding capacity for gossypol, and the majority of gossypol was located in the particulate fractions. Results of the present study provide information in understanding the regulatory mechanism of gossypol on antisteroidogenic and/or toxic effects in cultured bovine luteal cells.

Animals↗

Role of cyclic adenosine monophosphate (cAMP) in vitro on bovine oocyte maturation.

This experiment attempted to determine the effect of cAMP on maturation of bovine oocytes in chemically-defined, serum-free medium. Cumulus-oocyte complexes were incubated in modified DME/Ham F-12 medium containing dbcAMP at 0 (control), 10(-6), 10(-4) and 10(-2) M. After 18 and 24 hours of culture, the percentage of oocyte maturation between 0 (control) and 10(-2) M dbcAMP-treated groups were significant. Some oocytes were cultured with dbcAMP (10(-2) M) for 6, 12 and 24 hours followed by incubation in control medium to test the reversibility of inhibition or of any harmful effect of dbcAMP. The inhibitory effect of 10(-2) M dbcAMP on bovine oocyte maturation was reversed by transferring cumulus-oocyte complexes to the control medium. In addition, forskolin (0.12 and 0.24 mM) was effective (P < 0.01) in preventing the resumption of meiosis. The cAMP content of oocytes cultured with forskolin was not increased, although cumulus cells responded to forskolin with an increase in cAMP content. These results indicate that elevated levels of cAMP in the culture medium are important in regulating resumption of meiosis of bovine oocytes in vitro.

Journal Article↗

Air embolism-induced lung injury in isolated rat lungs.

Pulmonary air embolism causes physical obstruction of microvasculature and leads to permeability changes, release of mediators, and injury to lung tissue. In this study we employed an isolated perfused rat lung model to investigate the primary and secondary effects produced by infusion of air into the pulmonary artery. Infusion of various doses of air (0.10-0.25 ml) over a 1-min period produced a dose-dependent increase in pulmonary arterial pressure and lung weight gain. In contrast, when a constant air dose was administered over various periods of time (0.25 ml over 0.5-8.0 min), the pulmonary arterial pressure rose to the same extent regardless of the infusion rate, whereas the lung weight gain increased proportionately with the rate of infusion. Total vascular resistance rose from 1.41 +/- 0.04 to 5.04 +/- 0.09 mmHg.ml-1.min in rats given 0.25 ml air over 1 min (n = 14, P less than 0.001), with greater than or equal to 90% of this increase occurring in the arterial segments. Both thromboxane B2 and endothelin concentrations also increased in the perfusate, suggesting their involvement in this increased resistance. Furthermore the pulmonary filtration coefficient increased from 0.21 +/- 0.05 to 1.28 +/- 0.26 g.min-1.cmH2O-1.100 g (n = 8, P less than 0.001), and the protein concentration in lung lavage fluid also rose, indicating lung injury. Leukocyte counts in the perfusate were unaffected by embolization, but chemiluminescent activity was increased, indicating a possible role for activated leukocytes in lung injury induced by air emboli.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of pentoxifylline in the hamster zona-free oocyte spermatozoa penetration assay and on spermatozoa transmembrane migration motility.

The effects of pentoxifylline on capacitation, acrosome reaction and motility of spermatozoa in vitro were evaluated by the hamster zona-free oocyte penetration assay and the transmembrane migration method, respectively. The improvement in penetration capacity by the addition of pentoxifylline 40 min before coincubation had a trend toward statistical significance (0.05 less than less than 0.1) in normal fertile men and had statistical significance (p less than 0.05) in asthenospermic patients. There was no improvement by the addition of pentoxifylline 16 h before coincubation. Pentoxifylline significantly increased sperm motility in both normal (p less than 0.001) and asthenospermic patients (p less than 0.05) in the transmembrane migration method. This study showed that pentoxifylline could be used as a stimulant of in vitro sperm motility in male infertility.

Animals↗

Species difference in susceptibility to phorbol myristate acetate-induced leukopenia and lung injury: rat vs. dog.

Phorbol myristate acetate (PMA) was administered intravenously in a single dose to rats (400 micrograms/kg) and in a single and repeated doses to dogs (40 micrograms/kg). Severe leukopenia was observed in both species. The leukopenia in rats was due to a decreased number of both lymphocytes and neutrophils while the leukopenia in dogs was mainly due to a decreased number of neutrophils. The rats recovered from leukopenia much faster than the dogs. The dog which received a single injection developed focal fibrosis in the lungs. Rats showed only slight localized hemorrhage in the lungs, although the rats received a ten-fold larger dose of PMA than the dogs. Lungs of dogs which received multiple injections revealed severe hemorrhagic lesions in most alveoli. Lung lesions induced by PMA are thought to be mediated by activated leukocytes. This suggests that the severity of lung lesion correlates with the degree and duration of neutropenia. In conclusion, intravenous administration of PMA caused lung damage in rats and dogs. However, rats show much less sensitivity to PMA than dogs, resulting from the different response of leukocytes to PMA.

Animals↗

Rupture of rudimentary horn pregnancy.

A rare case of rupture of an noncommunicating rudimentary horn pregnancy is reported. The pregnancy proceeded to 25 gestational weeks, when the rudimentary horn ruptured. The patient had signs and symptoms of massive hemoperitoneum. An emergency exploratory laparotomy revealed rupture of the gravid rudimentary horn and the fetus was lying free in the peritoneal cavity, was delivered breech and died 2 hours later. This reproductive complication was treated successfully by prompt exploratory laparotomy. Some of the factors associated with pregnancy in a rudimentary horn are discussed.

Adult↗

[The activity of immunologic cells from peripheral blood, splenic venous blood and spleen in patients with advanced gastric cancer. A comparative study].

To elucidate the immunologic function of the spleen in AGC patients, peripheral blood lymphocytes (PBL), splenic venous blood lymphocytes (SVL) and spleen cells (SC) from 40 patients were tested for NK cell activity and T-cell subsets. Significant impairment of NK cell activity, decreased rate of CD+3 and CD+4 cells, declined CD+4/CD+8 ratio, and increased CD+8 cells were noted in SC of AGC patients as compared with PBL of normal subjects. NK cell activity and CD+4 cells of SVL and SC were significantly lower than those of PBL in AGC patients. More significant decline of CD+4/CD+8 cell ratio was found in SVL and SC when compared with PBL in AGC, mainly as a result of the marked decrease of CD+4 cells in SC. In conclusion, AGC tends to weaken the immune status of patients and the immunosuppressive role of the spleen would become more evident with the development of the tumor.

Adenocarcinoma↗