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Biomedical subjects

A Chan

Publications and source records attributed to A Chan.

At least 181 records · Page 10Linked to original sources

Terminations of pregnancy for exposure to oral retinoids in South Australia, 1985-1993.

The oral retinoids, isotretinoin and etretinate, are highly teratogenic drugs which have been available in Australia since 1985 because of their unique effectiveness in severe cystic acne, psoriasis and other keratinization disorders. Only dermatologists can prescribe them, but in spite of strict guidelines by the manufacturers and the College of Dermatologists, exposed pregnancies have occurred. We attempted to determine the circumstances of exposure to these drugs for the 18 pregnancies terminated in South Australia in 1985-1993, using questionnaires to medical practitioners who notified the terminations under legislation. The main reason for their occurrence was the lack of compliance with the use of effective contraception by the women. In South Australia, some prescriptions of oral retinoids by unauthorized doctors have been dispensed during this period. Using statistics on prescriptions dispensed, an estimate was made of 1 termination of pregnancy for 319 courses of treatment for women with isotretinoin. Extension of guidelines for prescription and more detailed counselling in relation to the use of contraception are recommended. It is also suggested that doctors intending to recommend terminations obtain consent to discuss exposure with the dermatologists concerned, who may not be aware of the exposed pregnancy.

Abortion, Induced↗

Porphyromonas gingivalis invasion of gingival epithelial cells.

Porphyromonas gingivalis, a periodontal pathogen, can invade primary cultures of gingival epithelial cells. Optimal invasion occurred at a relatively low multiplicity of infection (i.e., 100) and demonstrated saturation at a higher multiplicity of infection. Following the lag phase, during which bacteria invaded poorly, invasion was independent of growth phase. P. gingivalis was capable of replicating within the epithelial cells. Invasion was an active process requiring both bacterial and epithelial cell energy production. Invasion was sensitive to inhibitors of microfilaments and microtubules, demonstrating that epithelial cell cytoskeletal rearrangements are involved in bacterial entry. P. gingivalis, but not epithelial cell, protein synthesis was necessary for invasion. Invasion within the epithelial cells was not blocked by inhibitors of protein kinase activity. Invasion was inhibited by protease inhibitors, suggesting that P. gingivalis proteases may be involved in the invasion process. Low-passage clinical isolates of P. gingivalis invaded with higher efficiency than the type strain. Serum inhibited invasion of the type strain but had no effect on the invasion of a clinical isolate. Invasion of gingival epithelial cells by P. gingivalis may contribute to the pathology of periodontal diseases.

Blood Bactericidal Activity↗

An SEM examination of etched dentin and the structure of the hybrid layer.

The clinical requirements of dentin bonds are that they should be non-permeable to oral fluids, seal dentinal tubules, protect the pulp, and be long lasting and durable. Dentin bonding systems that use acidic agents to remove the smear layer are currently being used. Acid conditioning not only removes the smear layer, but also demineralizes the surface of the intertubular dentin and produces intratubular demineralization and funnelling. A dentin bond is produced when hydrophillic resin monomers infiltrate the dentinal tubules and collagen of the demineralized intertubular zone, producing a hybrid layer. The use of a critical point drying technique and SEM allows a clear visualization of the structure of the hybrid layer. This study showed that currently used hydrophillic resin monomers are unable to completely infiltrate the demineralized zone, and it is speculated that this failure could contribute to microleakage and influence the long-term durability of the bond. It is also apparent that these bonds depend on the mechanical investment of collagen by the infiltrating monomer. Since none of the unfilled resins tested seem capable of completely infiltrating the demineralized collagenous zone, the degree of demineralization produced by the commercial acid concentrations in current use is questioned. More dilute acids than those available commercially are shown to reduce both the degree and depth of demineralization, and we suggest that the resultant thinner layer may lend itself to more complete resin infiltration of the collagen.

Acid Etching, Dental↗

The composition and ultrastructure of resin tags in etched dentin.

PURPOSE: To examine in vitro the composition of resin tags in etched dentin by SEM and vital staining using Alcian Blue dye. MATERIALS AND METHODS: Bovine and human teeth were used. The dentin surface was exposed using water-irrigated #600 grit SiC paper and etched with varying dilutions of aquaeous solutions of phosphoric and maleic acid. Groups of 10 teeth per acid concentration were embedded in PMMA and Scotchbond Multi-Purpose (SMP) and cylinders of Z100 resin composite were bonded to their surfaces. These teeth were shear tested to failure and the failed surfaces subjected to SEM. Groups of three teeth per acid concentration had SMP and cylinders of Z100 bonded to their surfaces. These teeth were decalcified in concentrated HCL acid. The resultant cylinders and their attached resin tags were either subjected to SEM or stained with Alcian Blue dye. The latter specimens were embedded and prepared for light-microscopic examination. A further three human and three bovine teeth per acid concentration were etched and then prepared for SEM examination. All teeth for SEM were critical point dried. RESULTS: Resin tags were shown to consist of both resin and the glycosaminoglycans (GAG) sheath lining of the dentin tubule. As a result of the SEM observations, three mechanisms are suggested for the formation of resin tags, two of which will probably be found in vivo.

Acid Etching, Dental↗

Ruv and recG genes and the induced precise excision of Tn10 in Escherichia coli.

Induction of precise excision of Tn10 by UV or mitomycin C (MMC) is dependent on the expression of the SOS system. Ruv mutants of Escherichia coli, which are defective in DNA repair and recombination, showed diminished frequencies of both spontaneous and UV- or MMC-induced excision of Tn10 inserted in gal. RecG mutants, which are also defective in DNA repair and recombination, showed decreased induction of Tn10 excision with MMC, but not after UV treatment. A recG ruv double mutant showed a greater decrease in induction of excision with MMC than either single mutant. One can speculate that the Ruv proteins, which are known to be involved in the resolution of Holliday junctions, might also be involved in the resolution of putative intermediates generated during the precise excision of Tn10. RecG protein, whose function partially overlaps those of Ruv proteins, might also have some role in this process.

Bacterial Proteins↗

Expression complementary DNA library transfer establishes mrp as a multidrug resistance gene.

The emergence of drug-resistant cancer cells is a major obstacle to cancer treatment. Resistant cells often display a multidrug-resistant phenotype that reduces the promise of combination chemotherapy, the classic approach to the prevention of drug resistance. mdr1, a member of the ABC cassette superfamily of transporters which encodes an energy-dependent drug efflux pump, is the only gene known to confer the multidrug-resistant phenotype. Other multidrug resistance mechanisms must exist, since cell lines which have this phenotype in the absence of mdr1 overexpression have been described. We report here the application of a novel approach involving expression complementary DNA library transfer to the identification of drug-resistant genes. Using this approach we establish that mrp, a member of the ABC cassette superfamily of transporters, is capable of conferring a multidrug-resistant phenotype. This approach should be useful in the identification of other novel resistance genes.

3T3 Cells↗

RecN SOS gene and induced precise excision of Tn10 in Escherichia coli.

A mutant defective in the induced excision of Tn10 was isolated by decreased papillation on MacConkey-galactose plates with mitomycin C. The mutation involved was characterized as recN by genetic mapping and complementation. This mutant, as well as a previously characterized recN mutant (recN262), showed a markedly decreased frequency of excision of Tn10 after treatment with UV or mitomycin C. These observations indicate that recN is involved in the induced excision of Tn10.

DNA Repair↗

Polymerase chain reaction kinetics when using a positive internal control target to quantitatively detect cytomegalovirus target sequences.

High-performance liquid chromatography (HPLC) was used to detect and quantify cytomegalovirus (CMV) specific polymerase chain reaction (PCR) products generated during PCR co-amplification. PCR of CMV AD 169 or a plasmid which contains the CMV AD 169 native target sequence using the CMV primer set of Hsia et al. (J. Clin. Microbiol. 27, 1802-1809) generates a 152 bp PCR product. A CMV control sequence plasmid which shared the primer sequence of native CMV AD 169 but when amplified produces a larger 362 bp product was constructed. Under co-amplification conditions there was a linear relationship (over 3 logs) between the molar ratio of input CMV native and control target sequence and the molar ratio of the output PCR products as detected by HPLC despite differences between the two PCR target and product sizes. Co-amplifying known amounts of CMV control sequence plasmid as an internal standard allowed accurate quantitation of the amount of CMV native target sequence in a sample when the two PCR targets were present in approximately equimolar amounts +/- 1.5 log (coefficient of variation (CV) < 12%). By modifying the amount of CMV control target sequence plasmid used for co-amplification, accurate detection of the amount of CMV native sequence in samples could be extended to 5 logs, standard error (S.E.) < or = 16%. Precise quantitation of PCR targets using co-amplification PCR requires multiple sample dilutions to ensure that the CMV native target sequence was in a close equimolar relationship with the CMV control sequence at the time of PCR amplification.

Base Sequence↗

Two different glycosyltransferase defects that result in GalNAc alpha-O-peptide (Tn) expression.

This study shows for the first time that different glycosyltransferase defects in the biosynthesis of O-linked oligosaccharides give rise to the same GalNAc alpha-O-Ser/Thr determinant on Tn erythrocytes and colorectal carcinoma cells. The O-linked oligosaccharides isolated from the glycophorins of Tn erythrocytes contained predominantly alpha-N-acetylgalactosamine-O-Ser/Thr (Tn antigen) and sialyl-Tn. A marked reduction in normal sialylated oligosaccharides was also observed. Monoclonal antibody BRIC 111 raised against Tn erythrocytes reacted with both Tn erythrocytes and colorectal carcinoma tissues. Weak staining was detected in the supranuclear area and at the surface membranes in normal colorectal cells, but was absent from goblet cell vesicles. An increase in supranuclear staining over controls was found in tumour tissue and in the majority of resection margin specimens. The highest levels of staining were present in transitional mucosa, adjacent to the tumours where goblet vesicles were also positive. Glycosylation defects in the same patients were further studied by determination of the activity of glycosyltransferases in mucosal tissue from control and cancer patients. The reduction in or loss of beta 1-3 N-acetylglucosaminyl transferase activity to GalNAc-peptide in asialo-ovine submaxillary gland glycoprotein was detected by direct assay and by isolation of the oligosaccharides from the incubation products. No differences in N-acetylglucosaminyl-, galactosyl- or sialyl-transfer to Gal beta 1-3GalNAc in antifreeze glycoprotein or in sialyl transferase to asialo-ovine submaxillary gland glycoprotein were detected. Our study shows that the GalNAc alpha-O-Ser/Thr determinant on Tn erythrocytes and in colorectal carcinoma results from different glycosyltransferase defects in separate biosynthetic pathways for haematopoietic and epithelial tissues.

Antigens, Tumor-Associated, Carbohydrate↗

A multimegabase cluster of snRNA and tRNA genes on chromosome 1p36 harbours an adenovirus/SV40 hybrid virus integration site.

Adenovirus type 12 (Ad12) induces gaps at chromosomal bands 1p36, 1q21, 1q42-43 and 17q21 after infection of human embryonic kidney cells. Three of these bands harbour small nuclear RNA genes or pseudogenes, but the study of a possible relationship has been hampered by the lytic character of adenovirus infection. A non-lytic Ad5/SV40 hybrid virus preferentially integrates at 1p36 and the integration site has been cloned. Chromosomal band 1p36 encodes genes for small nuclear RNA U1 (RNU-1) and for the tRNAs of glutamic acid (TRE) and asparagine (TRN). Each of these genes is encoded by 15-30 copies. We studied the organization of these genes and of the viral integration site by pulsed field gel electrophoresis (PFGE) and analysis of yeast artificial chromosomes (YACs). We show that RNU-1, TRE and TRN genes are scattered over a region of probably more than 2 Mb with intergenic distances of up to 125 kb. The Ad5/SV40 integration site maps to identical chromosomal NotI fragments as RNU-1 and TRE. Fine mapping of a YAC shows that the integration site is within 40-70 kb of genes for RNU-1, TRN and TRE.

Adenoviruses, Human↗

Hyperinsulinaemia and Na+, K(+)-ATPase activity in thyrotoxic periodic paralysis.

OBJECTIVE: Thyrotoxic periodic paralysis (TPP) usually follows a heavy carbohydrate meal and this may be explained by hyperinsulinaemia stimulating Na+, K(+)-ATPase activity. To clarify this the effect of glucose load on serum insulin concentration and platelet Na+, K(+)-ATPase activity in thyrotoxic periodic paralysis (TPP) was examined. DESIGN: In all subjects a standard 75-g glucose tolerance test was done and blood samples were taken at 0, 1 and 2 hours. SUBJECTS: Twenty-five healthy controls (8 M and 17 F), 17 uncomplicated thyrotoxic patients (7 M and 10 F), 15 TPP patients who presented with paralysis and 4 TPP patients after treatment with antithyroid drugs. MEASUREMENTS: Plasma glucose was measured by the glucose oxidase method, serum insulin by radioimmunoassay and platelet Na+, K(+)-ATPase by the release of phosphate from ATP. RESULTS: TPP patients showed glucose intolerance (area under the curve (AUC) 16.5 +/- 4.4 (mean +/- SD) in TPP compared to 12.9 +/- 4.5 in controls (P < 0.01)) and hyperinsulinaemia (AUC 189.6 +/- 100.6 vs 98.5 +/- 53.4, P < 0.001). In uncomplicated thyrotoxicosis the results were similar to that in healthy controls. Platelet Na+, K(+)-ATPase were significantly higher in thyrotoxic patients compared to controls and in TPP patients were even higher. Ingestion of glucose increased platelet Na+, K(+)-ATPase in all groups. AUC for platelet Na+, K(+)-ATPase in TPP patients were significantly higher than in uncomplicated thyrotoxicosis (601 +/- 99.3 vs 482 +/- 109.4, P < 0.01) or healthy controls (320 +/- 107.3). In the 4 TPP patients studied after antithyroid treatment the results were similar to healthy controls. CONCLUSION: Patients with thyrotoxic periodic paralysis have hyperinsulinaemia and this is accompanied by higher Na+, K(+)-ATPase activity.

Adult↗

Association between serum uric acid and some cardiovascular risk factors in a Chinese population.

The association between serum uric acid concentration and some cardiovascular risk factors was examined in a working Hong Kong Chinese population (mean age 38 years), consisting of 910 men and 603 women. There was no significant age-related rise in serum uric acid concentration. Positive associations were found between serum uric acid concentration and body mass index, waist hip ratio, systolic and diastolic blood pressure, urea, creatinine, protein, glucose (fasting and 2 hours after 75 g oral glucose load), 2 hour insulin, triglycerides, and apolipoprotein B in men. Similar, but fewer, associations were seen in women, with the addition of a positive association with age. In both sexes, serum uric acid was negatively associated with high-density lipoprotein cholesterol. These findings complement the well-known clinical association between gout and cardiovascular and metabolic diseases, such as hypertension, hyperlipidaemia and diabetes mellitus, and suggest that serum uric acid may be a marker for the presence of an adverse cardiovascular risk factor profile.

Adult↗

Living arrangements of older Malaysians: who coresides with their adult children?

More than two-thirds of Malaysians age 60 or older coreside with an adult child. Data from the Senior sample of the Second Malaysian Family Life Survey (MFLS-2) are used to investigate which "seniors" (persons age 60 or older) live in this way. The analysis generally supports the notion that coresidence is influenced by the benefits, costs, opportunities, and preferences for coresidence versus separate living arrangements. For example, married seniors are more likely to coreside with adult children when housing costs are greater in their area or when the husband or wife is in poor health. This finding suggests that married parents and children live together to economize on living costs or to receive help with household services. Unmarried seniors who are better off economically are less likely to live with adult children, presumably because they use their higher incomes to "purchase privacy."

Adult↗

A human gene that shows identity with the gene encoding the angiotensin receptor is located on chromosome 11.

We report the cloning of a gene, intronless in its coding region, which we have named APJ. This gene was cloned using the polymerase chain reaction (PCR), with a set of primers designed on the basis of the conservation that members of G protein-coupled receptors (GPCR) have in their transmembrane (TM) regions. The putative receptor protein, APJ, shares closest identity to the angiotensin receptor (AT1) ranging from 40 to 50% in the hydrophobic TM regions of these receptors. The transcripts for this gene were detected in many regions of the brain. PCR analysis of somatic cell lines found APJ-related sequences to be only present on chromosome 11, and high-resolution mapping by fluorescence in situ hybridization (FISH) sublocalized APJ on band q12.

Amino Acid Sequence↗