Search PubMed⌕ Search

Biomedical subjects

L M Shi

Publications and source records attributed to L M Shi.

At least 19 recordsLinked to original sources
PubMed2004

A population-based study on the association between parental occupations and some common birth defects in singapore (1994-1998).

We sought to study the association between some common birth defects and parental occupations. The live births and congenital malformation born between January 1994 and December 1998 were obtained from the Singapore National Registry of Births and Deaths (the National Birth Defect Registry). The prevalence of overall birth defects among Singapore live births during the study period is 13.9 per 1,000 live births. The most frequent single coding defects were "bulbus cordis anomalies and anomalies of cardiac septal closure (BCA)," "congenital anomalies of urinary system (CUS)," "cleft palate and cleft lip (CPL)," and "certain congenital musculoskeletal deformities (CMD)." Using the "Legislators, Senior Officers & Managers" as reference and adjusting for possible confounders, there were significant associations for: (1) paternal "clerical workers" (adjusted RR 2.25) with the BCA; (2) maternal "professionals" with CUS (adjusted risk ratio [RR] 3.58); (3) paternal "production craftsmen and related workers" with both the BCA (adjusted RR 2.04), and the CMD (adjusted RR 2.83); (4) paternal "plant and machine operators and assemblers" with the BCA (adjusted RR 2.49), and the CUS (adjusted RR 5.19), and the CMD (adjusted RR 3.01). Paternal rather than maternal exposure might be more important in the causation of some common birth defects in Singapore.

Abnormalities, Multiple↗
PubMed2003

Parental occupations and other risk factors associated with nonchromosomal single, chromosomal single, and multiple birth defects: a population-based study in Singapore from 1994 to 1998.

OBJECTIVE: The purpose of this study was to evaluate the association between the prevalence of birth defects among maternal and paternal occupation groups in Singapore for live births between January 1, 1994, and December 31, 1998, and to determine whether there are certain demographic risk factors and maternal and/or paternal occupation groups that are associated with an increased risk for birth defects versus chromosomal single birth defect, nonchromosomal single birth defect, and multiple birth defects. STUDY DESIGN: This was a retrospective study. Information on live births (Singapore National Registry of Births and Deaths) and birth defect cases (National Birth Defects Register) were studied. Other information included the mother's date of birth, ethnic group, highest educational qualification, and the occupation of the mother and the father. Cox regression analysis was used to determine whether certain demographic and occupational factors were associated with the three groups of birth defects. RESULTS: Of a total of 237,755 live births, there were 3276 birth defect cases (nonchromosomal single birth defect, 1869 cases; chromosomal single birth defect, 197 cases; and multiple birth defects, 1210 cases). Increased risks for all types of birth defects were observed with advancing gestational age. Occurrence of nonchromosomal single birth defect and multiple birth defects were significantly higher for multiple births compared to singleton births. Significant associations were found with the use of "legislators, senior officers, and managers" as reference: Maternal occupation of "cleaners, laborers, and related workers" with chromosomal single birth defect anomalies (adjusted risk ratio, 4.86; 95% CI, 1.07-22.14); paternal occupation of "plant and machine operators and assemblers" (adjusted risk ratio, 1.50; 95% CI, 1.14-1.98) with nonchromosomal single birth defect; "production craftsmen and related workers" and "cleaners and laborers and related workers" with nonchromosomal single birth defect (adjusted risk ratio, 1.42; 95% CI, 1.10-1.82; and adjusted risk ratio, 1.43; 95% CI, 1.07-1.91 respectively); and multiple birth defects (adjusted risk ratio, 1.42; 95% CI, 1.03-1.94; and adjusted risk ratio, 1.47; 95% CI, 1.03-2.09, respectively). CONCLUSION: Maternal delivery age is an important risk factor for all birth defects. Mothers and fathers who work as "cleaners and laborers and related workers" appear to have a higher risk of giving birth to children with chromosomal single birth defect and nonchromosomal single birth defect and multiple birth defects, respectively. Further in-depth study would be needed to confirm these observations.

Abnormalities, Multiple↗
PubMed2002

Prevalence of birth defects and parental work in Singapore live births from 1994 to 1998: a population-based study.

The aims of the study were to assess the prevalence of birth defects (BDs) among different occupational groups and non-working parents, and to identify possible risk factors associated with BDs in Singapore live births born between 1 January 1994 and 31 December 1998. To do this, information on live births (from the Singapore National Registry of Births and Deaths) and BD cases [from the National Birth Defects Register (NBDR)] was obtained from 1 January 1994 to 31 December 1998. There were a total of 237 755 live births in Singapore between 1 January 1994 and 31 December 1998. Over the same period, 3293 cases of BDs were reported to the NBDR, giving an overall rate of 13.9 per 1000 live births. A downward trend with time was noted. Of the live born with BDs in this series, 36.7% presented with multiple anomalies. The overall occurrence of malformation (per 1000 live births) among working versus non-working mothers was 13.4 versus 14.2, respectively, and 13.8 for working fathers compared with 16.8 for non-working fathers. Parents in the occupational group 'Legislators, Senior Officers & Managers' had the lowest prevalence rates of congenital anomalies (9.4 per 1000 for mothers and 10.3 per 1000 for fathers), while the 'Agricultural & Fishery Workers' had the highest rates (40.0 per 1000 for mothers and 23.4 per 1000 for fathers). However, the very small number of workers in this latter group makes the rate unreliable. The prevalence of BDs in Singapore is comparable to those in other countries. Parental work per se is not correlated with BDs.

Adult↗
PubMed2001

Quantitative structure-antitumor activity relationships of camptothecin analogues: cluster analysis and genetic algorithm-based studies.

Topoisomerase 1 (top1) inhibitors are proving useful against a range of refractory tumors, and there is considerable interest in the development of additional top1 agents. Despite crystallographic studies, the binding site and ligand properties that lead to activity are poorly understood. Here we report a unique approach to quantitative structure-activity relationship (QSAR) analysis based on the National Cancer Institute's (NCI) drug databases. In 1990, the NCI established a drug discovery program in which compounds are tested for their ability to inhibit the growth of 60 different human cancer cell lines in culture. More than 70 000 compounds have been screened, and patterns of activity against the 60 cell lines have been found to encode rich information on mechanisms of drug action and drug resistance. Here, we use hierarchical clustering to define antitumor activity patterns in a data set of 167 tested camptothecins (CPTs) in the NCI drug database. The average pairwise Pearson correlation coefficient between activity patterns for the CPT set was 0.70. Coherence between chemical structures and their activity patterns was observed. QSAR studies were carried out using the mean 50% growth inhibitory concentrations (GI(50)) for 60 cell lines as the dependent variables. Different statistical methods, including stepwise linear regression, principal component regression (PCR), partial least-squares regression (PLS), and fully cross-validated genetic function approximation (GFA) were applied to construct quantitative structure-antitumor relationship models. For our data set, the GFA method performed better in terms of correlation coefficients and cross-validation analysis. A number of molecular descriptors were identified as being correlated with antitumor activity. Included were partial atomic charges and three interatomic distances that define the relative spatial dispositions of three significant atoms (the hydroxyl hydrogen of the E-ring, the lactone carbonyl oxygen of the E-ring, and the carbonyl oxygen of the D-ring). The cross-validated r(2) for the final GFA model was 0.783, indicating a predictive QSAR model.

Algorithms↗
PubMed2001

Structure-activity relationships for a large diverse set of natural, synthetic, and environmental estrogens.

Understanding structural requirements for a chemical to exhibit estrogen receptor (ER) binding has been important in various fields. This knowledge has been directly and indirectly applied to design drugs for human estrogen replacement therapy, and to identify estrogenic endocrine disruptors. This paper reports structure-activity relationships (SARs) based on a total of 230 chemicals, including both natural and xenoestrogens. Activities were generated using a validated ER competitive binding assay, which covers a 10(6)-fold range. This study is focused on identification of structural commonalities among diverse ER ligands. It provides an overall picture of how xenoestrogens structurally resemble endogenous 17beta-estradiol (E(2)) and the synthetic estrogen diethylstilbestrol (DES). On the basis of SAR analysis, five distinguishing criteria were found to be essential for xenoestrogen activity, using E(2) as a template: (1) H-bonding ability of the phenolic ring mimicking the 3-OH, (2) H-bond donor mimicking the17beta-OH and O-O distance between 3- and 17beta-OH, (3) precise steric hydrophobic centers mimicking steric 7alpha- and 11beta-substituents, (4) hydrophobicity, and (5) a ring structure. The 3-position H-bonding ability of phenols is a significant requirement for ER binding. This contributes as both a H-bond donor and acceptor, although predominantly as a donor. However, the 17beta-OH contributes as a H-bond donor only. The precise space (the size and orientation) of steric hydrophobic bulk groups is as important as a 17beta-OH. Where a direct comparison can be made, strong estrogens tend to be more hydrophobic. A rigid ring structure favors ER binding. The knowledge derived from this study is rationalized into a set of hierarchical rules that will be useful in guidance for identification of potential estrogens.

Animals↗
PubMed1998

Molecular modeling studies of the DNA-topoisomerase I ternary cleavable complex with camptothecin.

The present studies provide a three-dimensional model for the postulated ternary cleavable complex of topoisomerase I (top1), DNA, and camptothecin (CPT). Molecular simulations were done using the AMBER force field. The results suggest that a ternary cleavable complex might be stabilized by several hydrogen bonds in the binding site. In this proposed "drug-stacking" model, CPT is pseudointercalated in the top1-linked DNA cleavage site and interacts with the protein near its catalytic tyrosine through hydrogen bonding and stacking. The structural model is consistent with the following experimental observations: (i) the N3 position of the 5' terminal purine of the cleaved DNA strand is readily alkylated by 7-chloromethyl 10,11-methylenedioxy CPT; (ii) CPT generally tolerates substituents at positions 7, 9, and 10 but is inactivated by additions at position 12; (iii) 10,11-methylenedioxy (MDO) CPT is much more potent than 10,11-dimethoxy (DMO) CPT; (iv) the lactone portion of CPT is essential for top1 inhibitory activity; (v) 20S derivatives of CPT are much more potent than the 20R analogues; (vi) a catalytic tyrosine hydroxyl in top1 covalently links to the 3' terminal base, T, of the cleaved DNA strand; and (vii) top1 mutation Asn722Ser leads to CPT resistance. A total of 18 camptothecin derivatives with different DNA cleavage potencies were docked into the hypothetical cleavable complex binding site to test and refine the model. These studies provide insight into a possible mechanism of top1 inhibition by CPT derivatives and suggest rational approaches for the design of new CPT derivatives.

Amino Acid Substitution↗
PubMed1998

Mining the National Cancer Institute Anticancer Drug Discovery Database: cluster analysis of ellipticine analogs with p53-inverse and central nervous system-selective patterns of activity.

The United States National Cancer Institute conducts an anticancer drug discovery program in which approximately 10,000 compounds are screened every year in vitro against a panel of 60 human cancer cell lines from different organs. To date, approximately 62,000 compounds have been tested in the program, and a large amount of information on their activity patterns has been accumulated. For the current study, anticancer activity patterns of 112 ellipticine analogs were analyzed with the use of a hierarchical clustering algorithm. A dramatic coherence between molecular structures and their activity patterns could be seen from the cluster tree: the first subgroup (compounds 1-66) consisted principally of normal ellipticines, whereas the second subgroup (compounds 67-112) consisted principally of N2-alkyl-substituted ellipticiniums. Almost all apparent discrepancies in this clustering were explainable on the basis of chemical transformation to active forms under cell culture conditions. Correlations of activity with p53 status and selective activity against cells of central nervous system origin made this data set of special interest to us. The ellipticiniums, but not the ellipticines, were more potent on average against p53 mutant cells than against p53 wild-type ones (i.e., they seemed to be "p53-inverse") in this short term assay. This study strongly supports the hypothesis that "fingerprint" patterns of activity in the National Cancer Institute in vitro cell screening program encode incisive information on the mechanisms of action and other biological behaviors of tested compounds. Insights gained by mining the activity patterns could contribute to our understanding of anticancer drugs and the molecular pharmacology of cancer.

Antineoplastic Agents↗
PubMed1997

Quantitative structure-activity relationship of multidrug resistance reversal agents.

Multidrug resistance (MDR) is one of the major obstacles to long term successful cancer chemotherapy. The use of MDR reversal (MDRR) agents is a promising approach to overcome the undesired MDR phenotype. To design more effective MDRR agents that are urgently needed for clinical use, a data set of 609 diverse compounds tested for MDRR activity against P388/ADR-resistant cell lines was submitted to the MULTICASE computer program for structure-activity analysis. Some substructural features related to MDRR activity were identified. For example, the CH2-CH2-N-CH2-CH2 group was found in most of the active compounds, and the activity was further enhanced by the presence of (di)methoxylphenyl groups, whereas the presence of a stable quaternary ammonium salt, a carboxylic, a phenol, or an aniline group was found to be detrimental to activity. Possible explanations for these observations are proposed. Some physicochemical properties, e.g., the partition coefficient (log P) and the graph index (which in some sense measures the "complexity" of a molecule) were also found to be relevant to activity. Their role in MDRR was also rationalized. Based on our quantitative structure-activity relationship study of MDRR agents, some compounds with desired substructural features and activity were identified from the MACCS-II and National Cancer Institute DIS databases and tested experimentally. Our study may also help the rational design of anti-cancer drugs. Based on this study and on observations by other researchers, we postulate that P-glycoprotein-mediated resistance to paclitaxel could probably be eliminated by proper substitution of its benzamido and phenyl groups. Several novel compounds with the paclitaxel skeleton are proposed, which may lead to a new generation of paclitaxel anti-cancer drugs with less MDR potential.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Genetic diversity in the Chinese pangolin (Manis pentadactyla) inferred from protein electrophoresis.

We examined protein polymorphism of Chinese pangolins (Manis pentadactyla) from Yunnan Province of China, including two forms of three brown and nine dusky Chinese pangolins. Sixty-two genetic loci were screened; 12 loci were found to be polymorphic. The percentage of polymorphic loci (P) is 0.194, the mean individual heterozygosity (H) is 0.078, and the mean number of alleles (A) is 1.258. Furthermore, we calculated the genetic distance (D) between the two forms and found a low level of genetic divergence (D = 0.0206) between them, which indicates an almost-indistinguishable divergence at the level of proteins.

Alleles↗
PubMed1994

Multiple genotypes of mitochondrial DNA within a horse population from a small region in Yunnan Province of China.

mtDNA genotypes of six domestic horses (three adult short horses whose heights are under 1 m and three common domestic horses) from a small region of 15 km2 in Malipo county of Yunnan province of China were investigated by the technique of restriction fragment length polymorphism (RFLP) with 16 restriction endonucleases which recognize 6-bp sequences. An average of 56 fragments for an individual was obtained. Unlike other domestic animals, this population of horses exhibits high mtDNA genetic diversity. Each of the six horses has a specific mtDNA genotype showing a pattern of multiple maternal origins, as suggested by fossil and literature records. We think the population of horses is an amazing seed-resource pool of horses and hence deserves to be paid more attention from the view of conservation genetics. However, it is also remarkable that we did not find any typical mtDNA genetic markers which would discriminate between short horses and common domestic horses.

Animals↗
PubMed1994

Mitochondrial DNA polymorphism in natural populations of Drosophila albomicans (I)--Remarkable mtDNA polymorphism in the population of D. albomicans.

The technique of mtDNA restriction fragments length polymorphism (RFLP) was used to survey the population structure of D. albomicans. Remarkable mtDNA polymorphism has been observed in D. albomicans populations. A total of 34 nucleomorphs were detected from 82 isofemale lines assayed by only 8 restriction enzymes. The cause and the effect of this phenomenon were discussed. As a result, it is suggested that a mechanism which maintains mtDNA diversity exists in this fly, and that the high intra-populational polymorphism could numerically conceal the extent of differentiation between populations. In addition, on the base of restriction maps, it was found that the mtDNA molecule of D. albomicans might be impacted by the selection pressure during its evolution process both on the nucleotide composition and on the functional regions.

Animals↗
PubMed1993

Phylogenetic relationships of macaques as inferred from restriction endonuclease analysis of mitochondrial DNA.

Mitochondrial DNAs (mtDNAs) purified from 25 samples of 6 species of macaques, Macaca mulatta, M. fascicularis, M. arctoides, M. nemestrina, M. assamensis and M. thibetana, were analyzed to study the phyletic relationships among the species. A total of 36-46 sites was observed in each sample. By combining the cleavage patterns for each of the endonucleases, the 25 samples were classified into 11 restriction types. When data on M. fuscata and M. cyclopis collected by other authors were added to our own, the resultant molecular phylogenetic trees indicated that the 8 species may be divided into 4 groups: (1) M. mulatta, M. fuscata, M. cyclopis and M. fascicularis; (2) M. arctoides; (3) M. nemestrina; (4) M. assamensis and M. thibetana. Our results suggest that within both the fascicularis and sinica groups genetic distances are small between members and that the status of the species within the groups may require further investigation.

Animals↗
PubMed1991

Genetic diversity in the Chinese pangolin (Manis pentadactyla): inferred from restriction enzyme analysis of mitochondrial DNAs.

Two different forms of Chinese pangolins can be recognized according to the color of their scales, i.e., brown and dusky. We analyzed mitochondrial DNA (mtDNA) purified from the livers of seven dusky and six brown Chinese pangolins from the same locality, using cleavage patterns from 19 restriction enzymes. From the 19 6-bp recognition enzymes used, 51-56 sites were observed. By combining the cleavage patterns for each enzyme, the 13 samples were classified into four restriction types: two in dusky and two in brown Chinese pangolins. The estimated number of nucleotide substitutions per site in dusky and brown types is 0.002, and that between dusky and brown types is 0.012. Divergence between brown and dusky forms began 0.6 Myr ago, provided the mean rate of sequence divergence is 0.02 per Myr in mtDNA. Our results suggest that there is considerable divergence in Chinese pangolins, and brown and dusky Chinese pangolins may be quite different forms or, at least, belong to different maternal groups.

Animals↗
PubMed1990

Electron microscopic observations on the synaptonemal complex of spermatocytes of the giant panda (Ailluropoda melanoleuca).

Surface-spread and silver-stained preparations of spermatocytes from a giant panda were observed by electron microscopy for synaptonemal complex karyotyping. Ten pachytene spermatocyte nuclei were selected for length quantitation of SC. The mean relative lengths and centromeric indices of each SC agreed closely with those of the mitotic chromosomes. The pairing between lateral elements of autosomal chromosomes starts at early zygotene and leads progressively along their length to complete pairing at pachytene. The whole Y is paired with 1/3 length of X at mid-pachytene. The morphology of X and Y chromosome axes and the nonhomologous pairing of X and Y is discussed.

Animals↗
PubMed1990

[Kalman filtering-titrimetry: potentiometric titration of benzalkonium bromide].

The application of Kalman filtering and smoothing to titrimetry has been investigated. The method is suitable for titration systems in both thermodynamic equilibrium and non-equilibrium (dynamic). Particularly, Kalman filtering and smoothing can give correct results in cases when other traditional methods failed. The effect of model noise, titration rate and sampling time was also examined on the accuracy of the filtering titrimetry. The proposed method has been applied to potentiometric titration and rapid determination of benzalkonium bromide.

Benzalkonium Compounds↗
PubMed1990

[Mitochondrial DNA polymorphism in five species of the genus Macaca].

mtDNA from thirteen monkeys of five species (Macaca mulatta, M. nemestrina, M. assamensis, M. thibetana, M. arctoides) of the genus Macaca was analyzed with ten restriction enzymes, and compared with that of Japanese monkey (Macaca fuscata). Eight restriction types were observed among thirteen samples. There was extensive polymorphism in M. mulatta. The estimated number of nucleotide substitutions per site in M. mulatta is 0.012, and between these six species ranges from 0.016 to 0.091. Molecular phylogenetic tree of the mtDNA was constructed based on the genetic distance (P). The six species were divided into four groups: M nemestrina, M. arctoides, M. assamensis and M. thebitana, M. mulatta and M. fuscata. Our results support Fooden's (1976) classification of the genus Macaca into four species groups on the basis of morphologic data. Divergence times of the six species of the genus Macaca were also estimated on the mean rate of sequences divergence of 0.02 per million years in mtDNA.

Animals↗
PubMed1989

[Comparison of the common fragile sites and G-banding patterns of chromosomes among rhesus monkeys, white-eyebrow gibbons and human being].

The peripheral lymphocyte cultures from Rhesus monkeys (Macaca mulatta), White-eyebrow gibbons (Hylobates hoolock) and human being were treated with BrdU (bromodeoxyuridine), FrdU (fluorodeoxyuridine) and MTX (methotrexate). A number of 22 Common fragile sites for Rhesus monkeys and 20 for white-eyebrow gibbons were found. Chromosome homology and the relationship between fragile sites and chromosomal evolution were discussed. Several common fragile sites of human chromosomes have been found at the homologous chromosomal regions in Rhesus monkeys as well as in White-eyebrow gibbons. Furthermore, the fragile sites at 1q14, 1p32 of Rhesus monkey chromosomes may correspond to the homologous fragile sites at 1p21, 1q31 of White-eyebrow gibbons. All of these fragile sites at the homologous regions of chromosomes are evolutionarily conserved and may be the indicators of common origin of chromosomes as genetic markers. Combined with G-banding patterns of chromosomes, the conservative fragile sites at homologous regions of chromosomes may be useful for the study of chromosome homology and evolution in closely-related animals. Out results show that the differences of chromosome 1 between Rhesus monkeys and human may involve a pericentric inversion and a paracentric inversion. However, the differences of chromosome 1 between Rhesus monkeys and White-eyebrow gibbons may caused by a pericentric inversion, a pericentric inversion, and a deletion or a translocation. The main differences of chromosome 3 between Rhesus monkeys and human may involve a pericentric inversion. Out results indicate that the differences of chromosome 7 between White-eyebrow gibbons and human may involve a paracentric inversion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗