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Biomedical subjects

M F Cheng

Publications and source records attributed to M F Cheng.

At least 37 records · Page 2Linked to original sources
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

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

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↗
PubMed1995

Effect of inhibitors of poly(ADP-ribose) polymerase on the induction of GRP78 and subsequent development of resistance to etoposide.

We have recently demonstrated that cell lines deficient in poly(ADP-ribose) synthesis due to deficiency in the enzyme poly(ADP-ribose) polymerase (PADPRP) or depletion of its substrate NAD+ overexpress GRP78. Furthermore, this overexpression of GRP78 is associated with the acquisition of resistance to topoisomerase II-directed drugs such as etoposide (VP-16); (S. Chatterjee et al., Cancer Res., 54: 4405-4411, 1994). Thus, our studies suggest that interference with NAD+-PADPRP metabolism could provide an important approach to (a) define pathways of GRP78 induction, (b) study the effect of GRP78 on other cellular processes, (c) elucidate the mechanism of GRP78-dependent resistance to topoisomerase II targeted drugs, and (d) modulate responses to chemotherapy in normal and tumor tissues. However, in the in vivo situation, it is impractical to interfere with NAD+-PADPRP metabolism by mutational inactivation of PADPRP or by depletion of its substrate NAD+. Therefore, we have examined several inhibitors of NAD+-PADPRP metabolism including 3-aminobenzamide, PD128763, and 6-aminonicotinamide for their ability to reproduce the results obtained with cell lines deficient in NAD+-PADPRP metabolism relative to the induction of GRP78 and subsequent development of resistance to VP-16. Our studies show that 6-aminoicotinamide treatment is highly effective in the induction of GRP78 and subsequent development of resistance to VP-16, whereas treatment with 3-aminobenzamide or PD128763 does not induce GRP78 and thus does not result in VP-16 resistance.

6-Aminonicotinamide↗
PubMed1995

Poly(adenosine diphosphoribose) polymerase in peripheral blood leukocytes from normal donors and patients with malignancies.

A two-color flow cytometric technique was developed to analyze poly(ADP-ribose) polymerase (PADPRP) in different individuals as a function of different physiological or pathological conditions and to establish the basis for determining whether enzyme deficiency may predispose to degenerative or malignant disorders. Peripheral blood granulocytes were devoid of enzyme activity, whereas mononuclear cells had variable amounts. PADPRP was highest in B cells, intermediate in T cells, and lowest in monocytes. This pattern of enzyme distribution and relative enzyme content of different types of cells was remarkably constant in normal subjects. In a series of 66 normal donors there was no significant biological variation in enzyme content as a function of age, race, or sex. The mean PADPRP values in peripheral blood mononuclear cells from 81 random patient samples obtained from an ambulatory oncology clinic did not differ significantly from normal subjects. However, groups of patients with breast cancer, lymphocytic malignancies, and esophageal cancer were observed to have below normal levels for peripheral blood mononuclear cell PADPRP.

Adult↗
PubMed1994

Induction of M(r) 78,000 glucose-regulated stress protein in poly(adenosine diphosphate-ribose) polymerase- and nicotinamide adenine dinucleotide-deficient V79 cell lines and its relation to resistance to the topoisomerase II inhibitor etoposide.

Cell lines deficient in poly(ADP-ribose) synthesis due to enzyme deficiency (ADPRT54 and ADPRT351) or substrate deficiency (N2, N3, and N4) are resistant to topoisomerase II-directed agents, including etoposide (VP-16), N-[4-(9-acridinylamino)-3-methoxyphenyl]methanesulfonamide, and Adriamycin, relative to the effect of these agents on parental V79 Chinese hamster cells. Resistance is stable in the ADPRT54 and ADPRT351 cell lines, whereas resistance in the N2, N3, and N4 cell lines occurs when the cells are grown in nicotinamide-deficient medium to produce a state of NAD deficiency. However, sensitivity to VP-16 reverts to normal when cellular NAD levels return to control levels during growth in nicotinamide-containing complete medium. Poly(ADP-ribose) polymerase-deficient cell lines show constitutively increased levels of a protein at M(r) 78,000 on Coomassie blue-stained, sodium dodecyl sulfate-polyacrylamide gels that was subsequently confirmed with monoclonal antibodies to be M(r) 78,000 glucose-regulated stress protein (GRP78). Similarly, N2, N3, and N4 cells show induction of GRP78 under nicotinamide-deficient conditions. Induction of GRP78 is associated with elevated levels of GRP78 mRNA and appears to be regulated at the transcriptional level. When N3 cells with deficiency of poly(ADP-ribose) synthesis due to NAD deficiency are shifted to complete, nicotinamide-containing medium, they restore their NAD content, undergo a decrease in GRP78 levels, and regain sensitivity to VP-16. When V79 cells are shifted to nicotinamide-deficient medium they undergo a reduction in NAD content, followed by a progressive elevation in GRP78 levels, and they subsequently become increasingly resistant to VP-16. These studies demonstrate a clear association between deficiency of the NAD-poly(ADP-ribose) synthesis system, induction of GRP78 synthesis, and resistance to VP-16.

Animals↗
PubMed1994

Proposed pathways for vocal self-stimulation: met-enkephalinergic projections linking the midbrain vocal nucleus, auditory-responsive thalamic regions and neurosecretory hypothalamus.

In this study, we have investigated the neuroanatomical pathways that may underlie the influence of a female bird's vocal behavior upon her own reproductive endocrine response. We traced the ascending efferent projections of the midbrain vocal control nucleus, the intercollicularis (ICo), using an anterograde tracer, PHAL, delivered by iontophoretic application. We found labelled terminal fields in the anterior regions of the hypothalamus that contained luteinizing hormone releasing hormone- (LHRH) immunoreactive neurons. We injected into the LHRH-rich anterior medial hypothalamus (AM) the retrograde tracer, fluoro-gold, to verify the results of PHAL anterograde tracing and examine whether retrogradely labelled neurons in the ICo can be stained with met-enkephalin antiserum by the immunohistochemical method. Of the retrogradely labelled neurons in the medial division of ICo (mICo), between 5% and 15% were found to be met-enkephalin-immunoreactive positive perikarya. Our data suggest that axonal projections into the anterior medial hypothalamus may arise in part from enkephalin-immunoreactive neurons in the medial ICo. The mICo neurons distributed along the medial border of the midbrain auditory nucleus give rise to projections into the posterior medial hypothalamus (PMH) via synapses within the shell region of thalamic auditory nucleus, ovoidalis (Ov). We conclude that in the ring dove, the medial division of the vocal control nucleus, by virtue of its connection with the auditory thalamus and neurosecretory hypothalamus, is in a position to exert influence on endocrine response partly through enkephalinergic systems. Implications of similar connections in other species are discussed.

Animals↗
PubMed1994

Schedule-dependent cytotoxicity of topotecan alone and in combination chemotherapy regimens.

The schedule-dependent cytotoxic effects of topotecan were evaluated in tissue culture experiments with Chinese hamster V79 cells. One hour exposure to topotecan resulted in a typical phase-specific cell killing curve in which increasing concentrations kill progressively more cells and then reach a plateau when all susceptible cells are killed. In contrast, exposure for 24 h results in a steep concentration-response curve with no plateau. Other S-phase agents such as hydroxyurea or aphidicolin antagonized cytotoxicity when administered by simultaneous exposure with topotecan. Combinations of melphalan, BCNU (1,3 bis(2-chloroethyl)-1-nitrosourea), or cisplatinum with topotecan were most effective when cells were exposed to the alkylating agent or platinating agent during the first hour of a 24-h topotecan exposure. Combinations of topotecan with etoposide or adriamycin produce more cytotoxicity when topotecan is administered by prolonged exposure; however, there is no significant difference depending on whether the topoisomerase II inhibitor is added at the beginning or end of the topotecan exposure. These studies show the importance of appropriate dose scheduling to obtain optimal interaction of chemotherapeutic agents given in combination with topotecan.

Alkylating Agents↗
PubMed1993

Social condition affects the courtship behavior of male ring doves with posterior medial hypothalamic lesions.

Following bilateral lesions to the posterior medial hypothalamus (homologue of the mammalian ventromedial nucleus), adult male ring doves regain full courtship behavior and the ability to stimulate female egg-laying when housed continuously with females. Males with PMH lesions housed singly and only tested periodically with females continue to show deficits in courtship. These findings suggest that the social environment present in adulthood itself can directly influence recovery from brain lesions. They also demonstrate the importance of PMH in the mediation of male ring dove courtship behavior.

Animals↗
PubMed1993

Auditory-responsive units in the midbrain vocal nuclei in the ring dove (Streptopelia risoria).

The avian midbrain vocal control nucleus, n. intercollicularis (ICo), receives inputs from midbrain auditory nucleus and from a subdivision of auditory thalamus, suggesting a possibility of auditory response units in the ICo. Using single-unit recordings, we explored auditory response units throughout the dorsomedial midbrain of female ring doves under deep general anesthesia (acute preparation). We found exclusively in the ICo, units that responded preferentially to taped courtship coos of conspecifics (male or female coos) and units that responded to specific frequencies present in coos. Units in the midbrain auditory nucleus also responded to these auditory stimulation in a tonotopic fashion, and were responsive to tone burst as well. The results, along with data from other experiments, suggest that species-specific sound responsive units within the ICo may mediate acoustically facilitated female coos and endocrine responses of the ring dove.

Acoustic Stimulation↗
PubMed1993

Avian auditory pathways show met-enkephalin-like immunoreactivity.

Pathways associated with a recently defined region of the avian auditory thalamus, the shell of the nucleus ovoidalis (Ov), were examined for met-enkephalin immunoreactivity. The presence of enkephalin-like immunoreactive (ELI) perikarya within the medial margin of the inferior colliculus (ICM), afferent to the Ov shell, implicated ICM as a source of ELI fibers within the Ov shell and tract. The shell also contained ELI perikarya and its targets, including the ventromedial hypothalamus and caudoventral paleostriatal complex, were characterized by ELI fields. These data suggest that enkephalinergic auditory pathways, in parallel with traditionally recognized auditory projections, target regions of the avian basal forebrain.

Animals↗
PubMed1992

The shell region of the nucleus ovoidalis: a subdivision of the avian auditory thalamus.

The connectivity of a region surrounding the established thalamic auditory nuclei, n. ovoidalis (Ov) and n. semilunaris parovoidalis (SPO), was explored in the ring dove by using the anterograde tracers, Phaseolus vulgaris leucoagglutinin (PHAL) and biocytin, and the retrograde tracer, fluorogold. The Ov-SPO surround received a projection from a cell group along the interface of the auditory midbrain and the n. intercollicularis, as revealed with PHAL and biocytin, and was composed of neurons exhibiting a common morphology. These features and the presence of overlapping projections from different portions of the Ov-SPO surround suggest that this region comprises a functionally discrete area, which we term the Ov shell. Single unit recording within the shell established the existence of acoustically responsive units. Both PHAL and fluorogold labeling revealed a robust projection from the Ov shell to the caudomedial hypothalamus. Major telencephalic projections of the shell terminated within the ventral paleostriatal complex, "end-zones" of the field L, the caudomedial hyperstriatum ventrale, and regions immediately dorsal and lateral to the auditory neostriatum. Except for a portion of the shell bordering medial ovoidalis, PHAL injections into the shell also labeled fibers within the caudolateral neostriatum and along the lateral neostriatal rim. The connectivity of the Ov shell suggests that this region may integrate auditory pathways with brain regions associated with endocrine mediated behavior. In addition, the shell may constitute a source of converging input to several levels of central auditory pathways.

Acoustic Stimulation↗
PubMed1992

Role of catecholamines in the courtship behavior of male ring doves.

The role of catecholamines in the expression of male courtship behavior in ring doves was examined using central administration of pharmacological agents. Males treated with 6-hydroxydopamine or U-14,624, which depleted norepinephrine (NE) levels in the preoptic-hypothalamic area, showed increased levels of bow-coo and nest-coo displays. Conversely, males treated with tyramine or desipramine, which elevated NE levels in the preoptic-hypothalamic area, showed decreased levels of bow-coo and nest-coo displays. Drug-induced changes in dopamine levels were not consistent with any changes in behavior. This suggests that in the male ring dove NE in the preoptic-hypothalamic area is important in the expression of courtship displays.

Animals↗
PubMed1991

Alkylating agent hypersensitivity in poly(adenosine diphosphate-ribose) polymerase deficient cell lines.

Starting with the V79 cell line, two poly(ADP-ribose) polymerase deficient mutants, designated ADPRT 54 and ADPRT 351, had been shown to be hypersensitive to x- and UV-irradiation and to topoisomerase I inhibitors but to be resistant to topoisomerase II inhibitors (Chatterjee, S.; Cheng, M. F.; Berger, N. A. Hypersensitivity to clinically useful alkylating agents and radiation in poly(ADP-ribose) polymerase-deficient cell lines. Cancer Commun. 2:401-407;1990). We now report that these mutants were hypersensitive to a series of different alkylating agents, including alkylsufonates, alkylnitrosoureas, and nitrosoguanidine. In addition, they were hypersensitive to the UV-mimetic agent 4-nitroquinoline-1-oxide. Our findings provide strong evidence that poly(ADP-ribose) polymerase was involved in the repair of alkylating agent induced DNA damage as well as in the damage induced by UV- and x-irradiation and radiomimetic agents. The poly(ADP-ribose) polymerase deficient cell lines showed a marked decrease in the shoulder region of their survival curves, suggesting that poly(ADP-ribose) polymerase was involved in the repair of alkylating agent induced sublethal damage.

4-Nitroquinoline-1-oxide↗
PubMed1990

Hypersensitivity to clinically useful alkylating agents and radiation in poly(ADP-ribose) polymerase-deficient cell lines.

Mutant V79 Chinese hamster cell lines, deficient in poly(ADP-ribose) polymerase activity, were previously shown to be significantly resistant to etoposide, a topoisomerase II inhibitor, and hypersensitive to camptothecin, a topoisomerase I inhibitor (Chatterjee, S.; Trivedi, D.; Petzold, S.J.; Berler, N.A. Mechanism of epipophyllotoxin-induced cell death in poly(adenosine diphosphate-ribose) synthesis-deficient V79 Chinese hamster cell lines. Cancer Res. 50:2713-2718, 1990 and Chatterjee, S.; Cheng, M.F.; Trivedi, D.; Petzold, S.J.; Berger, N.A. Camptothecin hypersensitivity in poly(adenosine diphosphate-ribose) polymerase-deficient cell lines. Cancer Commun. 1:389-394; 1990). We have now demonstrated hypersensitivity of these mutant cell lines, designated ADPRT 54 and ADPRT 351, to a variety of antitumor agents including melphalan, BCNU, mitomycin, and bleomycin. They are also hypersensitive to UV- and x-irradiation. These mutants, however, are significantly resistant to the topoisomerase II-targeted DNA intercalators, Adriamycin and m-AMSA. Our results strongly suggest that inhibition of poly(ADP-ribose) polymerase could be useful to potentiate the cytotoxicity of a variety of currently available antitumor drugs.

Alkylating Agents↗