Search PubMed⌕ Search

Biomedical subjects

Y C Lin

Publications and source records attributed to Y C Lin.

409 records · Page 23Linked to original sources

Persistent hypertransaminasemia as the presenting findings of muscular dystrophy in childhood.

Prolonged elevation of the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) is often attributed to hepatic diseases. However, these enzymes are also present in a variety of extrahepatic tissues, including skeletal muscle. Five children (all boys) were referred to the pediatric department of the National Taiwan University Hospital because of persistent elevation of serum aminotransferase activities. The ages of these children were between 4 months and 5.5 years. The neurological findings were all not remarkable. The initial ALT and AST values were 114-581 U/L and 183-700 U/L, respectively. Serum creatine kinase was checked first after 0 to 30 months follow-up and found to be markedly elevated (range, 10,557 U/L to 62,508 U/L). Muscle biopsies in the five cases all showed degenerating and regenerating myofibers with interstitial fibrosis. In Cases 3, 4 and 5, complete absence of dystrophin immunoreactivity was found. Genetic studies showed deletions in the DMD gene (exons 45-48 in case 2 and 49-50 in case 4). This experience indicates that occult muscle diseases should be taken into account in patients with unexplained long-lasting hypertransaminasemia and therefore measurement of serum creatine kinase activity and muscle biopsy should be done early for the correct diagnosis of muscular dystrophy.

Alanine Transaminase↗

Identification of maturation-related wheat-germ lectin-binding proteins in the culture of human corpus epididymal epithelial cells.

This study is designed to investigate the synthesis of maturation-related wheat germ agglutinin (WGA) binding glycoproteins in the human corpus epididymal epithelial cells by in vitro culture. Epithelial cells were isolated from the corpus of human epididymides and cultured with RPMI 1640 medium supplemented with 10% fetal calf serum in type IV collagen-coated dishes at 37 degrees C. The epithelial nature, presence of fibroblasts, WGA-binding sites, and existence of GP-83 were determined by an indirect immunocytochemical and histochemical staining technique. Proteins in the cultured cells were analyzed by SDS-PAGE and autoradiography. After culturing for 10 days, the cells were shown to be positive with epithelial cell-specific keratins but devoid of fibroblasts. WGA-binding granules and positive binding sites of GP-83 were also detected in the cytoplasm. Immunoblots of cell extracts probed with the anti-GP-83 antibody from seminal fluid revealed the sperm maturation-related glycoprotein GP-83. The results indicate that WGA-binding proteins may be synthesized by the corpus epididymal epithelial cells of human and GP-83 may play an important role in sperm maturation. This culture model may be suitable for the investigation on the biosynthesis and physiology of human epididymal principal cells in vitro.

Animals↗

The effects of gossypol on the invasiveness of MAT-LyLu cells and MAT-LyLu cells from the metastasized lungs of MAT-LyLu-bearing Copenhagen rats.

Recently, we isolated a novel subline of the MAT-LyLu cell line from the metastasized lungs of MAT-LyLu-bearing Copenhagen rats (MLL cells). In this study, we compared the MLL cells to the parental MAT-LyLu cells with respect to invasive ability, mRNA expression level for the nm23 metastasis suppressor gene, and response to gossypol (GP), a natural compound with documented antiproliferative and antimetastatic activity, in an in vitro invasion assay. ML cells were isolated from mechanically dissociated metastasized lungs from MAT-LuLu-bearing Copenhagen rats. Comparisons of the invasive ability and steady-state levels of nm23 mRNA between MLL and MAT-LuLu cells were determined by in vitro invasion assay and RT-PCR, respectively. The results show that MLL cells display a higher penetration percentage than MAT-LyLu cells in the in vitro invasion assay. Furthermore, RT-PCR revealed that MLL cells possess lower steady state levels of nm23 mRNA than MAT-LyLu cells, suggesting a molecular basis for the observed differences in in vitro invasive ability. Finally, both MLL and MAT-LyLu cells were susceptible to gossypol, which induced dose-dependent inhibition of invasive activity. These results report the isolation of a novel, more highly invasive subline of the MAT-LyLu cell line that is as susceptible to the inhibitory effects of gossypol as the parental MAT-LyLu cells. The MLL cells, in combination with the parental MAT-LyLu cells, can be valuable tools for investigating the biology and behavior of metastatic cells and their response to chemotherapeutic/preventive agents.

Animals↗

Studies on the mechanism of positive inotropic effect of hymoquinolone.

Mechanism of positive inotropic action of hymoquinolone (7-hydroxy-8-methoxy-4(1H)-quinolone) (Q), a new compound isolated from Chinese Soft Sinularia polydactyla and Sinularia lettoclados, was studied using radioimmunoassay. Q caused positive inotropic action accompanied by elevated cAMP level in left and right atria of guinea pig at the concentration of 0.34 mM. The evidence that Q inhibited phosphodiesterase activity and did not affect adenylate cyclase activity led to the conclusion that Q may be an inhibitor of phosphodiesterase, thereby increasing cAMP level and producing positive inotropic actions.

Adenylyl Cyclases↗

Inhibition of xanthine oxidase by cytokinins and related substances.

Fourteen cytokinins were tested for their inhibitory effects on xanthine oxidase. The enzyme, xanthine oxidase catalyses the oxidation of hypoxanthine to xanthine and of xanthine to uric acid which has lambda max of 295 nm, forming the basis for a spectrophotometric assay of the activity of xanthine oxidase. The results showed that adenine-HCl, N6-(2-isopentenyl)-adenine, purine and DL-dihydrozeatin displayed very potent activities (IC50 = 1.92, 10.99, 60.98 and 86.36 microM respectively). Their apparent inhibition constants (Ki) were 2.20, 17.99, 13.59 and 115.62 microM, and induced competitive, uncompetitive, competitive and non-competitive type inhibitions respectively with respect to the substrate xanthine.

Adenine↗

Gossypol arrests human benign prostatic hyperplastic cell growth at G0/G1 phase of the cell cycle.

Recently we demonstrated that gossypol (GP), a male antifertility agent, is a potent inhibitor of malignant human prostate cancer cell growth that acts by arresting cells in G0/G1 phase and that this inhibitory effect may be mediated by transforming growth factor-beta 1 (TGF-beta 1). In this study we examined the effect of GP on the growth of prostatic cells from human benign prostatic hyperplasia (BPH) patients in vitro. Consistent with its inhibitory effect on the growth of malignant human prostate cancer cells, GP also acts as a potent inhibitor of cultured human BPH cell growth as assessed by thymidine incorporation assay. These results were confirmed by flow cytometric analysis which revealed that treatment of human BPH cells with increasing concentrations of GP resulted in a dose-dependent accumulation of cells in the G0/G1 phase with a concomitant decrease in cells progressing to the S and G2/M phases. Since inhibition of prostate cancer cells by GP appears to be mediated by TGF-beta 1, we also investigated the effect of GP on TGF-beta 1 gene expression in BPH cells. The results show that GP treatment resulted in a marked elevation of TGF-beta 1 gene expression indicating that TGF-beta 1 might be involved at least in part in the inhibitory pathway that is initiated by GP.

Cell Division↗

Inhibition of xanthine oxidase by synthetic cytokinin analogues.

Thirteen synthetic cytokinin analogues were tested for their inhibitory effects on xanthine oxidase. The enzyme, xanthine oxidase catalyses the oxidation of hypoxanthine to xanthine and of xanthine to uric acid, which has a gamma max of 295 nm, forming the basis for a spectrophotometric assay of the activity of xanthine oxidase. The results showed that 8-azaadenine(1), 4-amino-6-hydroxypyrazolo [3,4-d] pyrimidine(4), 4-amino-6-mercaptopyrazolo [3,4-d] pyrimidine(5) and 4-aminopyrazolo [3,4-d] pyrimidine(6) display inhibitory effects on xanthine oxidase with an order of activity of IC50 = 0.54, 5.91, 8.17 and 25.46 microM, respectively. Their apparent inhibition constants (Ki) were 0.66, 1.54, 6.61 and 26.79 microM, and induced mixed(competitive-non-competitive), competitive, mixed (competitive-non-competitive), and competitive types of inhibition respectively, with respect to the substrate xanthine.

Cytokinins↗

Estrogen-induced keratinocyte growth factor mRNA expression in normal and cancerous human breast cells.

The local recurrence rate of breast cancer has been reported to be unusually high at the surgical scar. Such breast cancer recurrence is believed to be triggered by the release of growth factors into the healing wound. Observations from an animal model have also demonstrated that KGF expression is dramatically induced by creation of full thickness wounds in mouse skin. Since KGF is an epithelial cell-specific mitogen in rat mammary epithelium, it is reasonable to speculate that KGF may be also involved in regulating human breast cancer cell growth. The purpose of the present study was to determine the effect of estradiol-17 on KGF gene expression in normal human breast stromal cells, as well as in human breast cancer stromal cells, and the mechanisms by which estradiol-17 regulates breast epithelial proliferation. Our results show that KGF expression was not effected by estradiol-17 treatment in normal human breast stromal cells. In contrast, KGF expression was stimulated by estradiol-17 in human breast cancer stromal cells. KGF mRNA levels have also been examined in normal human breast stromal cells and human breast cancer stromal cells. An interesting correlation was found between KGF expression and estradiol-17 regulation in these cell types. Normal human breast stromal cells which do not response to estradiol-17 have lower KGF mRNA level than the cancer cells which KGF expression is stimulated by estradiol-17. Our data also demonstrate that recombinant human KGF significantly stimulate normal human breast and human breast cancer epithelial cell proliferation in a dose-dependent manner. Since we have shown that estradiol-17 induces KGF mRNA expression in human breast cancer stromal cells, KGF may be involved at least in part in the stimulatory pathway that is initiated by estradiol-17 in human breast cancer epithelial cells.

Breast↗

A study to evaluate the parent-offspring similarity in the maxillofacial profile using fingerprints in Japanese families.

An attempt was made to investigate the parent-offspring similarity in the maxillofacial profile by a quantitative analysis of fingerprints. Lateral roentgenographic cephalograms and ten fingerprints were obtained from 98 Japanese patients (44 males and 54 females) and their parents. Analysis showed a significant parent-offspring correlation for both maxillofacial profile and fingerprints. The relatively low father-son correlation for both features suggests a major influence of X-linked genes. The genetic correlation between the maxillofacial profile and fingerprints was significant for parent-son but not for parent-daughter pairings. The parent-offspring correlation in the maxillofacial profile was evaluated in two groups showing differences (distant group) or similarities (near group) in the fingerprint patterns between the father and mother. In the distant group, a greater parent-offspring similarity was observed in the maxillofacial profile. The same finding was also obtained on using only digit II of the parents. Therefore, from a morphogenetical point of view, parental fingerprints appear helpful in clinical applications designed to predict maxillofacial growth in offspring.

Adolescent↗

Keratinocyte growth factor (KGF) induces aromatase activity in cultured MCF-7 human breast cancer cells.

Estrogen is the major hormonal stimulus for growth of the hormonal-dependent type of breast cancer. The rate-limiting step in the conversion of androgens to estrogens in breast tumors is catalyzed by aromatase, one of a series of related P-450 enzymes involved in the production of steroid hormones. An interesting correlation has been found between KGF mRNA and aromatase mRNA expression in human breast tumors. Tumors that express aromatase mRNA exhibit strong KGF expression, while tumors that do not express aromatase are weak or negative for KGF expression. Thus, it is reasonable to theorize that a possible association between KGF and aromatase in controlling human breast tumor growth exists. The purpose of the current study was to establish whether there is any interaction between KGF, which is known to have epithelial-specific mitogenic activity on breast cancer cells in vitro, and the synthesis of estradiol within the hormone-dependent breast cancer epithelial cells. In the present study, we have demonstrated that KGF stimulates aromatase activity in human breast cancer cells (MCF-7) in a dose-dependent manner. Our data shows that recombinant human KGF, at a dose as low as 10 ng/ml, can significantly increase aromatase activity 2-fold over controls. In agreement with this observation, we also found that aromatase mRNA levels were increased after 10 ng/ml KGF treatment in MCF-7 cells. These results indicate that the stimulatory effect of KGF on aromatase activity may be mediated by alterations in aromatase mRNA levels or in the efficiency of the translation of the message in MCF-7 cells. In addition, our results have demonstrated that modulation of aromatase activity appears to correlate with the stimulation of proliferative activity by KGF in MCF-7 cells. These results are consistent with our previous observations that estradiol-17 beta stimulates KGF expression in human breast cancer stromal cells, leading to the speculation that breast malignant transformation is associated with a positive feedback stimulation, whereby estradiol-17 beta stimulates breast cancer stromal cell production of KGF, and KGF subsequently stimulates aromatase activity in breast cancer cells, consequently raising levels of estradiol-17 beta, in turn acts on breast stromal cells to yield more KGF. Such a positive feedback loop could play an important role in the loss of growth control in human breast cancer cells.

Aromatase↗