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Biomedical subjects

H F Lin

Publications and source records attributed to H F Lin.

14 recordsLinked to original sources
PubMed2000

Ultraviolet radiation and reactive oxygen generation as inducers of keratinocyte apoptosis: protective role of tea polyphenols.

Ultraviolet A (UVA) radiation produces serious damage to skin, especially to dermis, but its damage to epidermis and responsible mechanisms are not fully understood. Studies were thus undertaken to investigate the effects of UVA or reactive oxygen species (ROS) on lipid peroxidation, cell cycle, and apoptosis in primary cultured rat keratinocytes and to determine the possible protective effects of tea polyphenols (TPP). UVA or ROS increased the release of plasma enzyme lactate dehydrogenase (LDH), and increased lipid peroxidation production (malondialdehyde, MDA), but decreased the activity of glutathione peroxidase (GSH-Px), indicating that UVA or ROS were cytostatic and peroxidizing to keratinocytes. TPP stabilized and protected cell membranes from ROS or UVA by inhibiting the release of LDH, lowering MDA levels, and increasing GSH-Px activity. Flow cytometry (FCM) analysis revealed that UVA or ROS decreased the proliferative index (PI); hence the cell growth was blocked in the S/G2 phase, with an increase in the percentage of apoptosis in primary keratinocytes. TPP modified the UVA or ROS-induced changes in PI and apoptosis. TPP may be useful to protect keratinocytes from UVA irradiation. In summary, these data demonstrated that UVA damage to skin keratinocytes in vitro was similar to that for ROS and that TPP protects against UVA-induced cytotoxicity by inhibiting lipid peroxidation and apoptosis.

Animals↗
PubMed1999

Correction of hemophilia B in canine and murine models using recombinant adeno-associated viral vectors.

Hemophilia B, or factor IX deficiency, is an X-linked recessive disorder occurring in about 1 in 25,000 males. Affected individuals are at risk for spontaneous bleeding into many organs; treatment mainly consists of the transfusion of clotting factor concentrates prepared from human blood or recombinant sources after bleeding has started. Small- and large-animal models have been developed and/or characterized that closely mimic the human disease state. As a preclinical model for gene therapy, recombinant adeno-associated viral vectors containing the human or canine factor IX cDNAs were infused into the livers of murine and canine models of hemophilia B, respectively. There was no associated toxicity with infusion in either animal model. Constitutive expression of factor IX was observed, which resulted in the correction of the bleeding disorder over a period of over 17 months in mice. Mice with a steady-state concentration of 25% of the normal human level of factor IX had normal coagulation. In hemophilic dogs, a dose of rAAV that was approximately 1/10 per body weight that given to mice resulted in 1% of normal canine factor IX levels, the absence of inhibitors, and a sustained partial correction of the coagulation defect for at least 8 months.

Animals↗
PubMed1999

Flow cytometric analysis of the toxicity of nitrofen in cultured keratinocytes.

Lactate dehydrogenase (LDH) release test, 3H-thymidine (3H-TdR) and 3H-leucine (3H-Leu) incorporation tests and flow cytometric analysis (FCM) of cell cycle were employed to elucidate cellular and molecular mechanism of nitrofen-induced toxicity in cultured keratinocytes. The results showed that cell morphologic damages were observed after exposure to 1.0 mmol/L and 10.0 mmol/L nitrofen. LDH release increased in a dose- and time-dependent manner. Depressions in 3H-TdR and 3H-Leu incorporation were found even at 0.01 mmol/L, and increased with the exposure dose. Cell cycle was analyzed from the DNA- histogram with propidium iodide stain. The results showed that there was no pronounced alteration in cell cycle after cells exposed to 0.01 and 0.1 mmol/L nitrofen. At dose of 1.0 mmol/L, S phase cells increased 2 times of that of control. With the increase of dose, G2/M phase cells became to increase about 5 times of that of the control. At 1.0 mmol/L, time course of cell cycle after exposure was observed. At the beginning of exposure, cells in S phase and G2/M phase were about 8.7% and 11%. Following 24 h incubation with nitrofen, cells in S phase increased to 18.0% with almost no change in G2/M. 72 h after exposure, G2/M phase cells increased to 63.3%. The above results demonstrated that S phase and G2/M phase blockage in cultured keratinocytes after exposed to nitrofen seems of importance in the mechanism of nitrofen-induced toxicity.

Animals↗
PubMed1999

Preliminary validation of tumor cell attachment inhibition assay for developmental toxicants with mouse S180 cells.

This study was designed to explore the possibility of using ascitic mouse sarcoma cell line (S180) to validate the mouse tumor cell attachment assay for developmental toxicants, and to test the inhibitory effects of various developmental toxicants. The results showed that 2 of 3 developmental toxicants under consideration, sodium pentobarbital and ethanol, significantly inhibited S180 cells attachment to Concanavalin A-coated surfaces. Inhibition was dependent on concentration, and the IC50 (the concentration that reduced attachment by 50%), of these 2 chemicals was 1.2 x 10(-3) mol/L and 1.0 mol/L, respectively. Another developmental toxicant, hydrocortisone, did not show inhibitory activity. Two non-developmental toxicants, sodium chloride and glycine were also tested and these did not decrease attachment rates. The main results reported here were generally similar to those obtained with ascitic mouse ovarian tumor cells as a model. Therefore, this study added further evidence to the conclusion that cell specificity does not limit attachment inhibition to Con A-coated surfaces, so S180 cell may serve as an alternative cell model, especially when other cell lines are unavailable. Furthermore, after optimal validation, it can be suggested that an S180 cell attachment assay may be a candidate for a series of assays to detect developmental toxicants.

Animals↗
PubMed1998

Human factor IX corrects the bleeding diathesis of mice with hemophilia B.

Mice with hemophilia B have been engineered using gene targeting techniques. These animals exhibit severe factor IX deficiency and a clinical phenotype that mirrors the human disease. We have bred the founder animals onto two different strains of mice, C57B1/6 and CD-1, and have sought to determine whether adenoviral vectors expressing human factor IX could correct the bleeding diathesis of mice with hemophilia B. Initial experiments showed that purified plasma-derived human factor IX added to murine factor IX-deficient plasma resulted in complete correction of the activated partial thromboplastin time (aPTT), and that injection of 10(11) particles of an adenoviral vector expressing human factor IX resulted in normalization of a modified aPTT in mouse plasma. As an additional method of assessing the function of human factor IX in the murine coagulation system, bleeding times were performed in normal, hemophilic, and adenoviral-treated hemophilic mice. By two different bleeding-time techniques, the treated hemophilic mice gave values identical to normal littermate controls, whereas the untreated hemophilic mice exhibited heavy blood loss and prolonged bleeding. There was a marked difference in antibody formation in the two strains of mice; 100% of the hemophilic CD-1 mice formed antibodies to human factor IX, but none of the C57B1/6 mice did. These data suggest that the C57B1/6 hemophilic mice will be more useful for gene transfer studies, while the CD-1 hemophilic mice may be of greater utility in studying the development of inhibitors.

Adenoviridae↗
PubMed1997

A coagulation factor IX-deficient mouse model for human hemophilia B.

Coagulation factor IX deficiency causes hemophilia B in humans. We have used gene targeting to develop a coagulation factor IX-deficient (factor IX-knockout) mouse strain. Mouse embryonic stem (ES) cells were targeted by a socket-containing vector that replaces the promoter through exon 3 of the factor IX gene by neoDeltaHPRT, which is a functional neo gene plus a partially deleted hypoxanthine phosphoribosyl transferase minigene. Chimeric mice generated using these socket-containing ES cells transmitted the targeted factor IX gene to their female offspring. Male offspring from these females were characterized and shown to exhibit a phenotype similar to hemophilia B. This factor IX-deficient mouse strain will be useful for studying gene therapy methods and structure-function relationships of recombinant factor IX proteins in vivo.

Animals↗
PubMed1994

Influence of in vitro methods, receptor fluids on percutaneous absorption and validation of a novel in vitro method.

In vitro experiment using excised skin has been valuable for studying the mechanism of percutaneous absorption. Based on previously established static diffusion cell system in this laboratory, a novel model-perfused glass diffusion cell system is designed. The results of initial comparative study on percutaneous absorption between glass perfused diffusion cell and static diffusion cell, in vitro and in vivo permeation as well as factors affecting permeation with seven radiolabelled chemicals are presented. The results demonstrate that the perfused diffusion cell system, which used a perfusion fluid below the surface of skin to take up the materials which penetrated the skin, is more similar to physiologic condition, convenient and automatic than that of the static cell. It well predicts the in vivo percutaneous absorption if appropriate receptor fluid is chosen. The results also show that the selection of receptor fluid is critical for in vitro permeation of chemicals with different solubility.

Animals↗
PubMed1991

The Drosophila maternal-effect gene fs(1)Ya encodes a cell cycle-dependent nuclear envelope component required for embryonic mitosis.

The maternal-effect gene fs(1)Ya is specifically required for embryonic mitosis in Drosophila. fs(1)Ya is involved in the initiation of the first embryonic mitosis and may also be necessary for subsequent embryonic mitotic divisions. fs(1)Ya encodes a 91.3 kd hydrophilic protein containing two putative MPF phosphorylation target sites and two potential nuclear localization signals. This protein is synthesized during postoogenic maturation from its maternal RNA and persists throughout embryogenesis. In early embryos, the fs(1)Ya protein is localized to the nuclear envelope from interphase to metaphase. During anaphase and telophase, it is dispersed in the nucleoplasm and cytoplasm, a behavior that is different from that of both the nuclear envelope and lamins. These results suggest that the fs(1)Ya protein is a cell cycle-dependent component of the nuclear envelope that specifically functions in embryonic mitosis.

Amino Acid Sequence↗
PubMedDate not supplied

Association between obesity and hyperlipidemia among children.

BACKGROUND: This study was undertaken to show the association between obesity and hyperlipidemia among the children. METHODS: In March 2000, while conducting a comprehensive health examination, we analyzed 2011 children from the first grade of primary schools in Taichung City in Taiwan. To study the association between obesity and hyperlipidemia, the t test, chi-square analysis, and multivariate logistic regression were used. RESULTS: There were 1057 boys (52.56 percent) and 954 girls (47.44 percent). The mean age was 7.27 +/- 0.46 years. The proportion of overweight was 11.07 percent in boys and 11.64 percent in girls. The proportion of obesity was 14.19 percent in boys and 12.89 percent in girls. After controlling the other covariates, the multivariate logistic regression analysis showed that overweight was associated with a low level of high density lipoprotein cholesterol. Obesity was associated with hypertriglyceridemia, a high level of low density lipoprotein cholesterol, and a low level of high density lipoprotein cholesterol. CONCLUSIONS: Our findings disclosed that the prevalence of overweight and obesity was high in childhood. Early intervention to control and prevent childhood obesity might be warranted. Obesity was associated with hyperlipidemia in children. A wide-scale survey will be suggested in the future to establish causal-effect issues between obesiyy and hyperlipidemia.

Body Weight↗