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Biomedical subjects

K F Cheng

Publications and source records attributed to K F Cheng.

At least 19 recordsLinked to original sources

A maximum likelihood method for studying gene-environment interactions under conditional independence of genotype and exposure.

Given the biomedical interest in gene-environment interactions along with the difficulties inherent in gathering genetic data from controls, epidemiologists need methodologies that can increase precision of estimating interactions while minimizing the genotyping of controls. To achieve this purpose, many epidemiologists suggested that one can use case-only design. In this paper, we present a maximum likelihood method for making inference about gene-environment interactions using case-only data. The probability of disease development is described by a logistic risk model. Thus the interactions are model parameters measuring the departure of joint effects of exposure and genotype from multiplicative odds ratios. We extend the typical inference method derived under the assumption of independence between genotype and exposure to that under a more general assumption of conditional independence. Our maximum likelihood method can be applied to analyse both categorical and continuous environmental factors, and generalized to make inference about gene-gene-environment interactions. Moreover, the application of this method can be reduced to simply fitting a multinomial logistic model when we have case-only data. As a consequence, the maximum likelihood estimates of interactions and likelihood ratio tests for hypotheses concerning interactions can be easily computed. The methodology is illustrated through an example based on a study about the joint effects of XRCC1 polymorphisms and smoking on bladder cancer. We also give two simulation studies to show that the proposed method is reliable in finite sample situation.

DNA-Binding Proteins↗

Retrospective analysis of case-control studies when the population is in Hardy-Weinberg equilibrium.

Association analysis of genetic polymorphisms has been mostly performed in a case-control setting in connection with the traditional logistic regression analysis. However, in a case-control study, subjects are recruited according to their disease status and their past exposures are determined. Thus the natural model for making inference is the retrospective model. In this paper, we discuss some retrospective models and give maximum likelihood estimators of exposure effects and estimators of asymptotic variances, when the frequency distribution of exposures in controls contains information about the parameters of interest. Two situations about the control population are considered in this paper: (a) the control population or its subpopulations are in Hardy-Weinberg equilibrium; and (b) genetic and environmental factors are independent in the control population. Using the concept of asymptotic relative efficiency, we shall show the precision advantages of such retrospective analysis over the traditional prospective analysis. Maximum likelihood estimates and variance estimates under retrospective models are simple in computation and thus can be applied in many practical applications. We present one real example to illustrate our methods.

Alcohol Dehydrogenase↗

Bayesian models for population-based case-control studies when the population is in Hardy-Weinberg equilibrium.

Association analysis of genetic polymorphisms has been mostly performed in a case-control setting with unrelated affected subjects compared with unrelated unaffected subjects. In this paper, we present a Bayesian method for analyzing such case-control data when the population is in Hardy-Weinberg equilibrium. Our Bayesian method depends on the informative prior which is the retrospective likelihood based on historical data, raised to a power a. By modeling the retrospective likelihood properly, different prior information about the studied population can be incorporated into the specification of the prior. The scalar a is a precision parameter quantifying the heterogeneity between current and historical data. A guide value for a is discussed in this paper. The informative prior and posterior distributions are proper under very general conditions. Therefore, our method can be applied in most case-control studies. Further, for assessing gene-environment interactions, our approach will naturally lead to a Bayesian model depending only on the case data, when genotype and environmental factors are independent in the population. Thus our approach can be applied to case-only studies. A real example is used to show the applications of our method.

Bayes Theorem↗

The use of an herbal formula by hospital care workers during the severe acute respiratory syndrome epidemic in Hong Kong to prevent severe acute respiratory syndrome transmission, relieve influenza-related symptoms, and improve quality of life: a prospective cohort study.

OBJECTIVES: To investigate the efficacy of an herbal formula in the prevention of severe acute respiratory syndrome (SARS) transmission among health care workers. The secondary objectives are to investigate quality of life (QOL) and symptomology changes among supplement users, and to evaluate the safety of this formula. DESIGN: Controlled clinical trial. SETTINGS: Hong Kong during epidemic of SARS. SUBJECTS: Two cohorts of health care workers from 11 hospitals in Hong Kong, 1 using an herbal supplement for a 2-week period (n = 1063) and a control cohort comprising all other health care workers who did not receive the supplement (n = 36,111) were compared prospectively. INTERVENTIONS: Taking an herbal supplement for a 2-week period. OUTCOME MEASURES: SARS attack rates and changes in quality of life and influenza-like symptoms were also examined at three timepoints among herbal supplement users. RESULTS: None of the health care workers who used the supplement subsequently contracted SARS compared to 0.4% of the health care workers who did not use the supplement (p = 0.014). Improvements in influenza-like symptoms and quality of life measurements were also observed among herbal supplement users. Less than 2% reported minor adverse events. CONCLUSION: The results of this pilot study suggest that there is a good potential of using Traditional Chinese Medicine (TCM) supplements to prevent the spread of SARS.

Adult↗

Using herbal medicine as a means of prevention experience during the SARS crisis.

At the peak of the SARS epidemic in Hong Kong, hospital workers were under high risks of contraction of the infection. Herbal preparations had been used historically in China to treat influenza-like diseases. During the SARS outbreak, herbal preparations had been used jointly with standard modern treatment in China. As a means to protect the at-risk hospital workers, an innovative herbal formula was created and consumed by 3160 of them in two weeks. During the two weeks, symptoms and adverse effects were close monitored; 37 of them had their serum checked for immunological responses. The results showed that none of the herb consumers contracted the infection, compared to 0.4% among the non-consumers. Adverse effects had been infrequent and mild. There were hardly any influenza-like symptoms and the quality of life improved. In the group who volunteered to have their immunological state checked, significant boosting effects were found. It was concluded that there might be a good indication for using suitable herbal preparations as a means of preventing influenza-like infection. The mode of preventive effect could be treatment of the infection at its very early stage instead of producing a period of higher immunological ability, as in the case of vaccination.

Adult↗

Interactions between modern and Chinese medicinal drugs: a general review.

While the use of health food and over-the-counter drugs for health promotion and adjuvant therapy is becoming increasingly popular, the concern about adverse effects is mounting. The possible adverse effects that may arise from drug interactions between these herbal preparations and standard modem therapy are equally worrying. Herbal toxicity and adverse effects are well documented in classical Chinese medicinal volumes. Interactions between herbal preparations and standard modem therapy are known. Extensive work needs to be done before useful guidelines can be established. However, based on available reports and clinical observations, some commonly used herbs and Chinese medicines have already demonstrated the need for special attention when used together with modern therapy. This paper analyzes the important material already available, and would serve as a preliminary checklist for patients who are taking herbal preparations, while at the same time receiving treatment from modern medicine.

Animals↗

Tandem conjugate reduction-aldol cyclization using Stryker's reagent.

[see reaction]. Conjugate reduction by Stryker's reagent to form copper enolates, followed by intramolecular aldol cyclization, successfully generated five- and six-membered carbocycles in one pot efficiently. This tandem reaction is generally diastereoselective and provides good yields of the beta-hydroxyketones without any dehydration at low temperatures.

Journal Article↗

Compounds from Kadsura ananosma.

The 18-(13-->12 beta)-abeo-lanostene triterpenoid acid, ananosic acid A (1), and the dibenzocyclooctadiene lignan, ananosin A (2), were isolated from the stem bark of Kadsura ananosma. Their structures were elucidated by extensive spectral studies and the structure of 1 was confirmed by single crystal X-ray diffraction analysis.

Crystallography, X-Ray↗

Cytotoxic oxoisoaporphine alkaloids from Menispermum dauricum.

Four new oxoisoaporphine alkaloids, daurioxoisoporphines A-D (1-4), were isolated from the rhizomes of Menispermum dauricum. The structures of these alkaloids were established by spectroscopic methods. The cytotoxic evaluation of 1 and 2 is reported against four cancer cell lines.

Adenocarcinoma↗

Diterpene glucosides from Pieris formosa.

Five diterpene glucosides, pierisformosides B-F were isolated from Pieris formosa D. Don (Ericaceae). Their structures were elucidated on the basis of spectral analysis. including 1H-1H COSY, 13C-1H COSY, HMBC and NOESY experiments.

Carbohydrate Conformation↗

A new trinortriterpenoid from Cleome chrysantha.

A new trinortriterpenoid, 1-epibrachyacarpone, was isolated from aerial parts of Cleome chrysantha. Its structure was elucidated as 1 by NMR investigations and X-ray crystallographic studies.

Crystallography, X-Ray↗

Four mono-tetrahydrofuran ring acetogenins, montanacins B-E, from Annona montana.

Four novel mono-tetrahydrofuran (THF) acetogenins, montanacins B-E (1-4), were isolated from the ethanolic extract of the leaves of Annona montana. The structures of 1-4 were established by spectroscopic methods and their absolute stereochemistries were determined by the advanced Mosher ester method. Montancins D (3) and E (4) bear a non-adjacent tetrahydropyran (THP) ring along with a THF ring and are the most unusual type of acetogenins discovered so far.

Furans↗

Induction of estradiol-2-hydroxylase and ethoxyresorufin-O-deethylase by 3-substituted indole compounds.

Estrogen can be hydroxylated at both 2- and 16alpha-positions. These two reactions are mutually exclusive. The 2-hydroxylated estrogen is relatively inactive compared with the 16alpha-derivative; hence, one approach in anti-estrogenic therapy is to look for drugs that can induce the 2-hydroxylation pathway. In the present study, using Balb/c and C57B/6 mice as the animal models, the induction effect of several isoprenyl compounds on estradiol-2-hydroxylase and ethoxyresorufin-O-deethylase activities was studied. The compounds examined included 2'- and 3'-methylbutadienyl-indoles and their respective acid condensation products, isopropyl indolocarbazole and yuehchukene; positional isomers of indole carbinols and carboxyaldehydes, as well as 3-methylcholanthrene, the prototype inducer of cytochrome P450 1A1. Our results demonstrated that while all of them were capable of inducing cytochrome P450 1A1-mediated ethoxyresorufin-O-deethylase activity, only the 3' isomers could induce estradiol-2-hydroxylase activity. The induction of these two activities did not show any direct correlation, suggesting that cytochrome P450 1A1 was not the same enzyme catalyzing both ethoxyresorufin-O-deethylation and estradiol-2-hydroxylation. Nevertheless, both inductions were mediated by the aryl hydrocarbon receptor. Among the compounds tested, yuehchukene showed competitive binding to estrogen receptor. This, together with the induction of estradiol-2-hydroxylase activity, may account for the anti-estrogenic effect of yuehchukene.

Alkaloids↗

Lignans from Kadsura angustifolia.

A new dibenzocyclooctadiene lignan named angustifolin D (1) together with four known lignans: kadsulignan L (2), kadsulignan N (3), schisantherin P (4) and meso-dihydroguaiaretic acid (5) were isolated from the stems of Kadsura angustifolia. Their structures and stereochemistries were elucidated by spectral studies. Compounds 2 and 5 showed moderate platelet-activating factor (PAF) antagonistic activities with IC50 values of 2.6 x 10(-5) and 4.1 x 10(-5) M, respectively.

Animals↗

Triterpenes and triterpenoid saponins from Mussaenda pubescens.

Two novel triterpenoid saponins, named mussaendosides U and V, together with one known saponin and four known triterpenes were isolated from the aerial parts of Mussaenda pubescens (Rubiaceae). The structures were determined on the basis of chemical analysis ad spectral methods. All these compounds were identified for the first time from the genus Mussaenda.

Carbohydrate Conformation↗

Growth characteristics of normal and dystrophic myoblasts in primary myoblast cultures.

This study employed immunocytochemistry and toluidine blue counterstaining to compare different procedures utilized in primary myoblast cultures, from which an optimal culture model for normal myoblasts could be derived. The growth characteristics of normal and dystrophic myoblasts were also investigated by means of this model. Results indicate that the requirements for an ideal myoblast culture should include a combined enzyme of 0.25% trypsin and 0.2% collagenase (type IV) (1:1), a preplating time of approximately 15-20 minutes, and a seeding density of 1 x 10(5) cells/ml. Furthermore, the mouse samples should be newborn mice. A better proliferative capacity of myoblasts was noted in an incubator with 10% CO2 coupled with Dulbecco's MEM plus 15% fetal calf serum. With regard to the growth characteristics of normal and dystrophic myoblasts, the doubling time of normal myoblasts was shorter than that of dystrophic myoblasts. In terms of the fusion percentage of myoblasts, dystrophic myoblasts tended to fuse earlier than normal ones, especially after 5 days in culture. The findings of this study are valuable in understanding the myogenesis of myoblasts under different culture conditions. The establishment of requirements for good growth of myoblast cultures will facilitate myoblast transfer therapy. Finally, the growth characteristics of normal and dystrophic myoblasts as well as variances in the proliferation and differentiation of these two types of cells are clarified.

Aging↗

Performance of older adults with and without cerebrovascular accident on the test of visual-perceptual skills.

OBJECTIVES: The purposes of this study were to (a) investigate whether older subjects with brain damage score lower on the Test of Visual-Perceptual Skills (TVPS) than control subjects without brain damage matched for age and education, (b) determine the demographic effects on test performance in both groups, and (c) determine the capacity of TVPS in identifying visual-perceptual deficits in adults with brain damage. METHOD: The study sample consisted of 22 subjects with cerebrovascular accident (CVA) and 155 subjects who were neurologically intact (control group). The TVPS was administered individually to each subject. Raw scores (total response time and accuracy) were analyzed to generate descriptive statistics. Other statistical analysis included analysis of variance, analysis of covariance, discriminant analysis, and Pearson product-moment correlations. RESULTS: There were significant between-group differences on all TVPS measures, with control subjects performing better than subjects with CVA. Age was shown to affect performance on most subtests of the TVPS in the control group. Education had significant influence over each measure, whereas gender differences were significant only in two subtests. No demographic effects were found in the group with CVA. The total TVPS accuracy score was the most powerful discriminator between the two groups, correctly classifying 74.4% of the subjects. Finally, the total accuracy score inversely correlated with total time score. CONCLUSION: The TVPS may be useful in screening for visual-perceptual impairments in adults with CVA. Age, gender, and educational level have no significant impact on the magnitude of visual-perceptual dysfunctions.

Age Factors↗