Biomedical subjects

J F Chiu

Publications and source records attributed to J F Chiu.

At least 19 recordsLinked to original sources

PubMed2000

Suppressed oxidant-induced apoptosis in cadmium adapted alveolar epithelial cells and its potential involvement in cadmium carcinogenesis.

Apoptosis involves a series of genetically programmed events associated with endonucleolytic cleavage of DNA. This process is triggered by a variety of agents, including oxidants such as hydrogen peroxide (H(2)O(2)) and it plays a key role in eliminating pre-neoplastic cells from the lung. Failure to do so could favor tumor promotion. The current study demonstrated that alveolar epithelial cells, adapted to cadmium (CdCl(2)) by repeated in vitro exposure, exhibit lower levels of H(2)O(2)-induced apoptosis than similarly challenged non-adapted cells. An immunologic assay, measuring cytoplasmic histone-associated DNA fragments, indicated maximal apoptosis 24 h after exposure to 400 microM H(2)O(2). Non-adapted cells showed a 13-fold increase in oxidant-induced apoptosis while Cd-adapted cells had only a 4-fold elevation. A terminal deoxyribonucleotidyl transferase mediated dUTP nick end labeling (TUNEL) method was used to assess the percentage of cells with DNA breaks consistent with apoptosis. Cd-adapted and non-adapted cells that were not exposed to H(2)O(2) did not differ in TUNEL positivity. However, after H(2)O(2) treatment, the percentage of TUNEL positive cells was 4-fold higher in non-adapted cultures than in adapted ones. Suppression of oxidant-induced apoptosis is due, in part, to up-regulation in the gene expression of several resistance factors including metallothioneins (MT-1 and MT-2), glutathione S-transferases (GST-alpha and GST-pi), and gamma-glutamylcysteine synthetase catalytic subunit (gamma-GCS). These steady-state mRNA changes, determined by Northern blotting, were accompanied by increased levels of MT and gamma-GCS protein, GST activity, and glutathione (GSH). Suppressed oxidant-induced apoptosis, resulting at least in part from these response modifications, could leave pre-neoplastic or neoplastic cells alive, favor clonal expansion, and ultimately lead to cancer development.

Adaptation, Biological↗

PubMed2000

Experimental study of the effects of Optison concentration on sonoporation in vitro.

Lethal sonoporation and reparable sonoporation were observed in Jurkat lymphocytes in suspension with the addition of varying amounts of Optison, a commercially available bubble-based contrast agent. For given ultrasound (US) exposure conditions (spatial peak-pressure amplitude of 0.2 MPa, duty cycle 10% and 2-MHz frequency), sonoporation was directly related to the bubble-to-cell ratio (in a range from 0 to 230). It was found that the nearest bubble-cell spacing was also related to the occurrence frequency of bioeffects. A constant bubble-to-cell ratio often provided very different results for two different initial cell concentrations (200,000 cells/mL and 600,000 cells/mL), with the higher cell concentration generally exhibiting higher levels of sonoporation. In contrast, a constant bubble-to-cell spacing provided similar results between the two initial cell concentrations. The frequency of reparable and lethal sonoporation was seen to decay as the inverse-cube power of the nearest bubble-cell spacing. Significant reparable sonoporation was observed at a bubble-cell spacing that was 10 microm larger than the minimum spacing at which significant lethal sonoporation was observed. Preliminary analysis also suggests the possibility of a step-wise increase in lethal sonoporation as spacing decreases; further experiment is needed.

Albumins↗

PubMed2000

Cadmium-mediated oxidative stress in alveolar epithelial cells induces the expression of gamma-glutamylcysteine synthetase catalytic subunit and glutathione S-transferase alpha and pi isoforms: potential role of activator protein-1.

Exposure of rat alveolar epithelial cells to 10 micromol/L CdCl2 causes time-dependent increases in steady-state mRNA levels of the gamma-glutamylcysteine synthetase catalytic (heavy) subunit (gamma-GCS) and of glutathione S-transferase isoforms (GST-alpha and GST-pi). The expression of gamma-GCS was significantly increased as early as 2 h after addition of cadmium. Maximal induction of gamma-GCS mRNA (approximately 4-fold), at 8 h, was subsequently followed by increases in gamma-GCS activity/protein and glutathione (GSH) levels. Maximal elevations in GST-pi (approximately 2-fold) and GST-alpha (approximately 10-fold) transcripts, at 8 and 24 h, respectively, were also accompanied by enhanced GST activity. Cadmium-induced oxidative stress, assessed by alterations in GSH homeostasis and an accelerated rate of intracellular oxidant production, could constitute early events in the signal transduction pathway mediating these responses. The dimeric transcription factor, activator protein-1 (AP-1), may also play a regulatory role in this process. This association is suggested by transcriptional activation of the immediate-early response genes, c-fos and c-jun, within 15 min after exposure to cadmium and by the enhancement of AP-1 DNA binding activity, involving a c-Jun protein complex, which is maximally induced (approximately 4-fold) by 2 h. These molecular changes likely function together to protect alveolar epithelial cells against cadmium toxicity.

Animals↗

PubMed2000

Glucocorticoids maintain the extracellular matrix of differentiated mammary tissue during explant and whole organ culture.

Mouse mammary whole organ culture (WOC) and explant culture of lactating tissue were used to investigate the mechanism by which glucocorticoids maintain secretory epithelium following lobuloalveolar development. The relative number of mammary epithelial cells expressing glucocorticoid receptors did not change with the loss of secretory epithelium during involution as demonstrated with competitive binding assays and immunohistochemistry for the glucocorticoid receptor. Furthermore, glucocorticoids did not inhibit AP-1 binding activity. However, Northern analysis demonstrated that genes associated with the breakdown of the extracellular matrix were not expressed in tissues cultured with glucocorticoids, in contrast to their upregulation during involution of mammary tissue cultured with insulin alone. Tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNA expression was lowest in tissue cultured in the presence of glucocorticoids and increased 2.3-, 3.4-, and 9-fold when tissues were involuted in the presence of insulin (Ins) alone, Ins and hydrocortisone (Hyd) with 0. 005 mg/ml, or 0.01 mg/ml collagenase IV, respectively. These data indicate that glucocorticoids maintain mammary differentiation in part by inhibiting the turnover of basement membrane.

Animals↗

PubMed1999

Promoter competitors as novel antifibrotics that inhibit transforming growth factor-beta induction of collagen and noncollagen protein synthesis in fibroblasts.

A single-stranded 27-mer phosphorothioate oligodeoxynucleotide (ssPT) containing the transforming growth factor-beta (TGF-beta) response element was synthesized. Rat fetal lung fibroblasts were stably transfected with the ColCat 3.6 plasmid, which contains a portion of the 5'-flanking region of the proalpha1(I) collagen gene linked to the chloramphenicol acetyltransferase (CAT) gene. The cells were transiently transfected with the modified oligodeoxynucleotides in both the presence and absence of bleomycin, a fibrogenic antineoplastic agent. At 50 microg ssPT, the bleomycin-induced increase in CAT activity was abrogated. The ability of ssPT to inhibit collagen synthesis in rat fetal lung fibroblasts was determined. Single-stranded PTs inhibited both collagen synthesis and noncollagen protein synthesis induced by TGF-beta1, the mediator of the bleomycin fibrogenic effect. Inflamed granulation tissue fibroblasts were prepared from polyvinyl alcohol sponges implanted in the backs of rats. These fibroblasts were treated with various doses of ssPTs in the presence and absence of TGF-beta1. Single-stranded PTs also blocked both the TGF-beta1-induced increase in collagen synthesis and noncollagen synthesis in these fibroblasts. However, the TGF-beta1-induced increase in collagen and noncollagen protein synthesis was not blocked by ssPTs containing a mutated TGF-beta response element. In addition, ssPT did not significantly alter the basal levels of collagen and noncollagen protein synthesis in rat lung fibroblasts or in granuloma derived fibroblasts. Since dexamethasone was also able to block the TGF-beta1-induced increase in collagen and noncollagen protein synthesis (Meisler et al., [1997] J. Invest. Dermatol. 108:285-289), these data indicate that phosphorothioate oligodeoxynucleotide antifibrotic agents mimic the inhibitory effect of glucocorticoids on collagen synthesis without the untoward side effects of these steroids.

Animals↗

PubMed1999

Characterization of cadmium-induced apoptosis in rat lung epithelial cells: evidence for the participation of oxidant stress.

The mode of cadmium-induced cell death was investigated in a rat lung epithelial cell line. Cells, grown to near confluence, were exposed to 0-30 microM CdCl2 for 0-72 h. Phase contrast microscopy and fluorescent nuclear staining showed that Cd caused morphological alterations in lung epithelial cells that are characteristic of apoptosis. These changes included cell shrinkage, detachment of the cell from its neighbors, cytoplasmic and chromatin condensation, and fragmentation of the nucleus into multiple chromatin bodies surrounded by remnants of the nuclear envelope. Apoptotic DNA degradation was validated and quantitated using a sensitive enzyme-linked immunosorbent assay (ELISA) which measures the amount of histone-bound DNA fragments in the cytosol. Using this technique, a maximum level of apoptosis (5-fold higher than control) was observed in cultures exposed for 48 h to 20 microM CdCl2. The terminal deoxyribonucleotidyl transferase mediated dUTP nick end labeling method (TUNEL) was subsequently used to determine the percentage of cells that contained Cd-induced DNA strand breaks. After 48 h, approximately 54% of the cells exposed to 20 microM Cd were TUNEL positive compared to less than 2% for control cells. Although the mechanisms by which Cd initiates apoptosis in these cells are presently not known, reactive oxygen species are likely to play a role. This possibility is supported by the finding that the first morphological features indicative of apoptosis were preceded by the up-regulation of oxidant stress genes (glutathione S-transferase-alpha, gamma-glutamylcysteine synthetase, and metallothionein-1), activation of redox sensitive transcription factors (AP-1 and NF-kappaB), and changes in various forms of glutathione (reduced, oxidized, and protein-bound).

Animals↗

PubMed1999

Identification of a cis-acting element in the rat alpha-fetoprotein gene and its specific binding proteins in F9 cells during retinoic acid-induced differentiation.

Mouse F9 embryonic teratocarcinoma stem cells can be induced to differentiate into visceral endoderm. Following retinoic acid (RA) treatment, alpha-fetoprotein (AFP), a differentiation marker, is expressed and secreted. The mechanism by which RA regulates AFP expression during differentiation is not clear. The relatively late induction of AFP indicates that the AFP gene may not be a primary target of RA activity during F9 cell differentiation. In this study, a CAT reporter plasmid containing the rat AFP 5'-regulatory region (-7040 to +7) adjacent to the CAT gene (pAFPCAT) was stably transfected into F9 cells and used to delineate a cis-acting element which associates with AFP gene activation. Similar spatial and temporal expression patterns between the transcriptional activity of the recombinant AFP gene and the endogenous AFP gene demonstrate that this stably transfected F9 system can be used to dissect both cis-elements and trans-acting factors responsible for RA-induced AFP expression. Using a series of deletion mutants of the pAFPCAT, the region between -2611 to -1855 was found to be important in AFP-induction. Subsequent analysis identified a functional sequence (-1905 to -1891, 5'-ACTAAAATGGAGACT-3') that differentially binds nuclear proteins from undifferentiated and differentiated F9 cells. This sequence, designed as differentiation-associated sequence (DAS) for its unique binding of a nuclear protein (DAP-II) that appears during RA-induced F9 differentiation, acts as a regulatory protein factor in AFP gene activation.

Animals↗

PubMed1999

Ultrasound-induced cell lysis and sonoporation enhanced by contrast agents.

The enhancement of ultrasound-induced cell destruction, lysis, and sonoporation in low cell concentration suspensions (2 x 10(5)/mL) by the presence of contrast agents (gas bubble to cell ratio = 230) was demonstrated using cervical cancer cells (HeLa S3) suspensions containing micron-size denatured albumin microspheres filled with air (Albunex) or octafluoropropane (Optison). The suspensions were insonificated by 2-MHz continuous or tone burst ultrasound in near field. The spatial peak-pressure amplitude was 0.2 MPa. The enhancement of cell destruction due to Optison was shown to be much higher than that due to Albunex for similar bubble concentration and ultrasound conditions. For tone burst exposures, significant lysis and sonoporation only occurred in the presence of a contrast agent. The majority of the bioeffects observed occurred in the first 5 min of exposure. The relationship between the enhancement of bioeffects and duty cycle of tone burst ultrasound appears to indicate that both stable gas spheres of contrast agents and cavitation nuclei created by the disruption of the gas spheres play a significant role in causing the bioeffects.

Cell Death↗

PubMed1997

Estrogen affects development of alveolar structures in whole-organ culture of mouse mammary glands.

In order to determine if estrogen affects lobulo-alveolar development, and to determine if whole organ culture of mouse mammary glands is an appropriate model of estrogen effects on mammary development, mouse mammary glands were cultured in the presence or absence of phenol red and estrogen. Lobulo-alveolar development did not occur in vitro when phenol red was eliminated from culture medium. Lobulo-alveolar development was stimulated by 17 beta-estradiol in a dose dependent manner over a physiological range. These results support the hypothesis that estrogen plays a critical role in alveolar development in the mammary gland. In this report an in vitro model of mammary development is identified in which the effects of estrogen are morphologically described and quantified.

Aldosterone↗

PubMed1997

Cancer mortality and residence near petrochemical industries in Taiwan.

An ecologic study design was used to investigate the relationship between cancer risks and residence in communities adjacent to petrochemical industrial counties (PICs). Directly age-adjusted mortality rates for cancer during 1982-1991 among 16 counties characterized by a heavy concentration of petrochemical industries were compared to rates among 16 matched counties with similar concentration of nonpetrochemical manufacturing industries, urbanization level, and demographic characteristics. An excess rate for liver cancer among males was found in the so-called PICs. The correlation could not be explained by confounding variables such as urbanization, socioeconomic class, or employment in nonpetrochemical industries. No other increased cancer risks were found to be associated with residence near petrochemical industries.

Age Factors↗

PubMed1997

Damp housing conditions and respiratory symptoms in primary school children.

There is evidence that indoor air pollution contributes to the development of respiratory symptoms. This study examined the relationships between dampness in houses and respiratory symptoms in 4,164 primary school children in the subtropical rural areas of the Kaohsiung region, Taiwan. Dampness in homes was assessed by questionnaires that reported 1) general dampness, 2) mold or mildew inside the home, or 3) flooding (appearance of standing water within the home, water damage, or leaks of water into the building). Evidence for upper and lower respiratory symptoms were also collected by questionnaires. Recorded symptoms included cough, wheezing, pneumonia, bronchitis, and asthma. Degrees of dampness were reported as 12.2%, 30.1%, and 43.4%, respectively by the parents or guardians of the study population. The prevalence of respiratory symptoms was consistently higher in homes with indications of dampness than in non-damp homes. After adjustments for potential confounders, selected respiratory symptoms among the childhood population were significantly higher in damp than non-damp homes, with the exception of pneumonia. We conclude that dampness in the home is a strong predictor of and risk factor for respiratory symptoms and constitutes a significant public health problem in subtropical area.

Child↗

PubMed1997

Effects of indoor environmental factors on respiratory health of children in a subtropical climate.

This study was conducted to determine whether indoor environmental factors affected respiratory symptoms in 4164 primary school children in Kaohsiung rural areas of Taiwan. Information on respiratory health symptoms and characteristics of the housing was obtained using a written questionnaire, completed by the parents of children. Multiple logistic regression analysis examined the relationship between respiratory health symptoms (cough, wheezing, bronchitis, asthma, and allergic rhinitis) and housing factors. Home dampness was significantly associated with all respiratory health symptoms. Incense burning and mosquito repellant burning showed effects on the reporting of coughing symptoms. No apparent associations were found with the other indoor factors included in this study or respiratory health symptoms. We conclude that dampness in the home has a pronounced effects on respiratory health symptoms and is a new public health issue in subtropical areas.

Air Pollution, Indoor↗

PubMed1997

Long-term vegetarian diet and bone mineral density in postmenopausal Taiwanese women.

This study examined bone density among postmenopausal Buddhist nuns and female religious followers of Buddhism in southern Taiwan and related the measurements to subjects characteristics including age, body mass, physical activity, nutrient intake, and vegetarian practice. A total of 258 postmenopausal Taiwanese vegetarian women participated in the study. Lumbar spine and femoral neck bone mineral density (BMD) were measured using dual-photon absorptimetry. BMD measurements were analyzed first as quantitative outcomes in multiple regression analyses and next as indicators of osteopenia status in logistic regression analyses. Among the independent variables examined, age inversely and body mass index positively correlated with both the spine and femoral neck BMD measurements. They were also significant predictors of the osteopenia status. Energy intake from protein was a significant correlate of lumbar spine BMD only. Other nutrients, including calcium and energy intake from nonprotein sources, did not correlate significantly with the two bone density parameters. Long-term practitioners of vegan vegetarian were found to be at a higher risk of exceeding lumbar spine fracture threshold (adjusted odds ratio = 2.48, 95% confidence interval = 1.03-5.96) and of being classified as having osteopenia of the femoral neck (3.94, 1.21-12.82). Identification of effective nutrition supplements may be necessary to improve BMD levels and to reduce the risk of osteoporosis among long-term female vegetarians.

Adult↗

PubMed1997

Gastric cancer mortality and drinking water qualities in Taiwan.

The possible association between the risk of gastric cancer and nitrate and hardness in drinking water from municipal supplies was investigated in a matched case-control study in Taiwan. Data on gastric cancer deaths among eligible residents in Taiwan from 1987 through 1991 (6,766 cases) were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes (6,766 controls) and were matched individually to the cases by sex, year of birth, and year of death. Data on nitrate-nitrogen (NO3-N) and hardness levels in drinking water throughout Taiwan were collected from the Taiwan Water Supply Corporation (TWSC). The municipality of residence for cases and controls was assumed to be the source of the subject's nitrate and hardness exposure via drinking water. There was no difference in gastric cancer rates between the groups with different levels of nitrate. The odds ratios (95% confidence interval) for death from gastric cancer was 0.95 (0.87-1.03) for the group with water nitrate levels between 0.23 and 0.44 mg/L, and 1.02 (0.93-1.11) for the group with nitrate levels greater than 0.45 mg/L. However, the results show a significant negative relationship between drinking water hardness and gastric cancer mortality. Odds ratios were 1.16 (1.07-1.26) and 1.65 (1.52-1.79), respectively, for exposure to moderately hard water and soft water compared with the use of hard water. This is an important finding for the Taiwan water industry and human health risk.

Case-Control Studies↗

PubMed1997

Geographic variations in mortality from motor vehicle crashes in Taiwan.

Mortality from motor vehicle crashes within five urbanization categories in Taiwan between 1981 and 1990 was investigated. Sex-specific standardized mortality ratios (SMRs) were calculated within each urbanization category for motor vehicle crash deaths. Most urban areas demonstrated lower SMRs for both males and females. In contrast, most rural areas exhibited higher SMRs for both males and females. Both males and females demonstrated a significant linear relationship between decreasing urbanization and increasing SMRs for motor vehicle crash mortality. A variety of factors may underlie the inverse correlation between SMRs for motor vehicle crashes and urbanization category. These data are most useful in generating hypotheses for further studies to define specific etiological factors operating within urbanization categories.

Accidents, Traffic↗

PubMed1997

Calcium and magnesium in drinking water and risk of death from colon cancer.

The possible association between the risk of colon cancer and the levels of calcium and magnesium in drinking water from municipal supplies was investigated in a matched case-control study in Taiwan. All eligible colon cancer deaths (1714 cases) of Taiwan residents from 1989 through 1993 were compared with deaths from other causes (1714 controls), and the levels of calcium and magnesium in drinking water of these residents were determined. Data on calcium and magnesium levels in drinking water throughout Taiwan were obtained from the Taiwan Water Supply Corporation. The control group consisted of people who died from other causes and the controls were pair-matched to the cases by sex, year-of-birth, and year-of-death. The adjusted odd ratios (95% confidence interval) were 0.79 (0.64-0.98) for the group with water calcium levels between 24.4 and 42.3 mg/liter and 0.58 (0.47-0.73) for the group with calcium levels of 42.4 mg/liter or more. The adjusted odd ratios were not statistically significant for the relationship between magnesium levels in drinking water and colon cancer. The results of the present study show that there is a significant protective effect of calcium intake from drinking water against colon cancer.

Aged↗

PubMed1997

Regulation and activities of alpha-fetoprotein.

alpha-Fetoprotein (AFP) is one of the major serum proteins in the early life of mammals. The function of this protein is not yet fully understood. AFP is an oncodevelopmental gene product which is expressed at high levels in the embryonic yolk sac and fetal liver. The synthesis of AFP decreases dramatically after birth. Only trace amounts of AFP are synthesized in the adult liver. However, expression of the AFP gene is reactivated in the adult during liver regeneration and hepatocarcinogenesis. AFP is an excellent model system for studying the temporal and tissue-specific regulation of oncodevelopmental gene expression. Experiments with transgenic mice and DNA transfection studies have revealed several transcriptional control regions and cis-acting elements in the AFP gene. A large number of trans-acting protein factors interacting with these cis-acting elements have also been identified. Recent studies demonstrated that expression of AFP is regulated by at least two major signal transduction pathways in response to extracellular stimuli. The interactions between steroid hormone receptors and transcriptional factors which respond to separate signal transduction pathways result in transcriptional regulation of AFP gene expression. Trans-acting protein factors or steroid receptors complexed with given response elements can display different activities in different cell types due to cross-talk among both local protein-protein interactions within the DNA-binding domain, and distal protein-protein interactions. However, the detailed mechanisms of AFP gene expression are still not completely understood.

Animals↗

PubMed1997

Magnesium and calcium in drinking water and cerebrovascular mortality in Taiwan.

The relationship between death from cerebrovascular disease and the levels of magnesium and calcium in drinking water was examined using an ecological design. The study area consisted of 227 municipalities in Taiwan. Data on the levels of magnesium and calcium in drinking water have been collected from the Taiwan Water Supply Corporation (TWSC). These levels of magnesium and calcium were compared using the standardized mortality ratios (SMRs) for cerebrovascular disease (1981-1990). A statistically significant inverse relationship was present between cerebrovascular mortality and levels of both magnesium and calcium after adjusting for urbanization index. After adjustment for calcium levels in drinking water and urbanization index, the weighted multivariate-adjusted regression coefficient indicated a decrease of 0.248 in the standardized mortality ratios (SMRs) for every 100 mg/L increase in magnesium levels in drinking water. The results from this study strengthen the hypothesis that magnesium in drinking water helps to prevent death from cerebrovascular disease.

Calcium↗