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Biomedical subjects

C T Chan

Publications and source records attributed to C T Chan.

At least 55 records · Page 3Linked to original sources
PubMed1997

Counselling dilemmas associated with the molecular characterisation of two Angelman syndrome families.

We report the molecular characterisation of two families with Angelman syndrome referred for prenatal diagnosis, in which atypical molecular findings resulted in counselling dilemmas. The first is a familial case of Angelman syndrome in which the two affected children have mutations which affect the imprinting mechanism, as shown by the presence of paternal DNA methylation patterns at D15S63 and SNRPN and biparental inheritance of 15q11-q13 markers. DNA prepared from a 21 week fetal blood sample detected a fetus with normal maternal and paternal DNA methylation patterns at D15S63, but inheritance of the same maternal chromosome 15q11-q13 as the two affected sibs. This is probably a result of germline mosaicism in the mother. The second is a case of Angelman syndrome with an atypical deletion of 15q11-q13, which involves both unusual proximal and distal breakpoints. The deletion was characterised in order to assess the risk of Angelman syndrome in a second pregnancy in the mother of this child.

Angelman Syndrome↗
PubMed1995

Comparative evaluation of a commercial enzyme immunoassay for the detection of human antibody to Rickettsia typhi.

A commercial enzyme immunoassay kit called the Dip-S-Ticks (DS) for the detection of total immunoglobulin (Ig) G and IgM human antibodies to Rickettsia typhi was evaluated. In tests with 340 serum samples from patients with diagnosed cases of rickettsial diseases, patients suffering from other febrile illnesses, and normal subjects, the DS compared favorably with the standard indirect fluorescent-antibody (IFA) test. At IFA cutoff titers of > or = 1.64 and > or = 1:128, the DS showed sensitivities of 88.2 and 91.4% and specificities of 91.8 and 87.7%, respectively. The DS test correlated significantly with both the IFA IgG (r = 0.84, P < 0.0005) and IgM (r = 0.63, P < 0.0005) titers. Only 80% of IgG and 82% of IgM IFA readings determined by two technicians were within one dilution, while the DS was more reliable, with 100% within one dot. The rapidity, reliability, and simplicity of the DS suggest that it is a suitable test for use in clinical laboratories unable to perform the IFA test.

Antibodies, Bacterial↗
PubMed1994

Angelman syndrome associated with a maternal 15q11-13 deletion of less than 200 kb.

Angelman syndrome (AS) is a neurogenetic disorder arising from a lack of genetic contribution from the maternal chromosome 15q11-13. To date, the AS critical region has been defined by an inherited deletion of approximately 1.5Mb, spanning the 3-21 (D15S10), LS6-1 (D15S113) and GABRB3 loci. We have identified an individual with the typical features of AS who has a deletion of the maternal chromosome which encompasses LS6-1, but does not extend to either flanking marker. This deletion, initially detected by (CA)n repeat analysis, was further characterised by fluorescence in situ hybridisation (FISH) using cosmids derived from a 260 kb LS6-1 yeast artificial chromosome (YAC). Neither end cosmid from this YAC clone falls within the deletion, suggesting that the minimal AS region is less than 200 kb. We also studied three loci within 15q11-13 which detect parent-of-origin specific DNA methylation imprints, and found that both normal maternal and paternal patterns were present in this patient.

Angelman Syndrome↗
PubMed1993

Molecular mechanisms in Angelman syndrome: a survey of 93 patients.

Angelman syndrome (AS) results from a lack of maternal contribution from chromosome 15q11-13, arising from de novo deletion in most cases or rarely from uniparental disomy. These families are associated with a low recurrence risk. However, in a minority of families, more than one child is affected. No deletion has been found in these families, except one. The mode of inheritance in these families is autosomal dominant modified by imprinting. Sporadic cases, with no observable deletion, therefore pose a counselling dilemma as there could be a recurrence risk as high as 50%. We present a series of 93 AS patients, showing the relative contribution of these different genetic mechanisms. Eighty-one AS patients were sporadic cases while 12 cases came from six families. Sixty cases had deletions in 15q11-13 detected by a set of highly polymorphic (CA)n repeats markers and conventional RFLPs. Ten sporadic cases plus all 12 familial cases had no detectable deletion. In addition, two cases of de novo deletions occurred in a chromosome 15 carrying a pericentric inversion. In one of these the AS child had a cousin with Prader-Willi syndrome (PWS) arising from a de novo deletion in an inv(15) inherited from his father. One case arose from a maternal balanced t(9;15)(p24;q15) translocation. There were three cases of uniparental disomy. Five patients were monoallelic for all loci across the minimal AS critical region, but the presence of a deletion cannot be confirmed. In familial cases, all affected sibs inherited the same maternal chromosome 15 markers for the region 15q11-13. Two cases were observed with a de novo deletion starting close to the locus D15S11 (IR4-2R), providing evidence for the development of classical AS with smaller deletions. Cytogenetic analysis proved limited in its ability to detect deletions, detecting only 42 out of 60 cases. However, cytogenetic analysis is still essential to detect chromosomal abnormalities other than deletions such as inversions and balanced translocations since both have an increased risk for deletions. A staged diagnostic strategy based on the use of highly informative (CA)n repeat markers is proposed.

Angelman Syndrome↗
PubMed1993

The gene encoding the calcium binding protein calcyclin is expressed at sites of exocytosis in the mouse.

Calcyclin is a member of the S100 family of calcium binding proteins. We have found by in situ hybridization that calcyclin transcripts are restricted to specific cell types within a limited number of mouse organs. High levels of expression in the epithelia lining the gastrointestinal, respiratory and urinary tracts, and specific localization of the transcripts to the goblet cells in the small intestine, lead us to suggest a role for calcyclin in the process of mucus secretion. In addition, calcyclin expression was detected in the corpus luteum, placenta and nerves within the gut wall, which are all sites of regulated exocytosis. We propose that this S100-like protein may be part of a calcium signalling pathway utilized in the secretion of various products by different cell types.

Age Factors↗
PubMed1992

Expression of the L14 lectin during mouse embryogenesis suggests multiple roles during pre- and post-implantation development.

A cDNA encoding L14, the lactose-binding, soluble lectin of relative molecular mass 14 x 10(3), has been isolated in a differential screen designed to identify genes that are regulated during the differentiation of murine embryonic stem cells in vitro. The expression patterns of the gene and of the encoded protein during mouse embryogenesis are consistent with the lectin playing a role at several stages of development. Firstly, it is initially synthesised in the trophectoderm of expanded blastocysts immediately prior to implantation, suggesting that it may be involved in the attachment of the embryo to the uterine epithelium. Secondly, in the postimplantation embryo, the lectin is abundantly expressed in the myotomes of the somites. This observation, when taken together with data indicating a role for the lectin in myoblast differentiation in culture, suggests that the protein is important in muscle cell differentiation. Finally, within the nervous system expression of this gene is activated early during the differentiation of a particular subset of neurones.

Animals↗
PubMed1991

Modes of transmission for Ascaris lumbricoides and Trichuris trichiura among Chinese children in Macao City.

To obtain more information on the transmission of Ascaris lumbricoides and Trichuris trichiura in Macao City, 308 Chinese children were surveyed. The infection rates of A. lumbricoides and T. trichiura were 14.9 and 6.8%, respectively. There was no association between the infections. A. lumbricoides infection was associated with age and T. trichiura with new immigrants from China. No association was found between the infections and family socio-economic factors. The results suggest that the modes of transmission for A. lumbricoides and T. trichiura may be different in highly urbanized areas.

Adolescent↗
PubMed1991

The murine H19 gene is activated during embryonic stem cell differentiation in vitro and at the time of implantation in the developing embryo.

The differentiation in vitro of murine embryonic stem cells to embryoid bodies mimics events that occur in vivo shortly before and after embryonic implantation. We have used this system, together with differential cDNA cloning, to identify genes the expression of which is regulated during early embryogenesis. Here we describe the isolation of several such cDNA clones, one of which corresponds to the gene H19. This gene is activated in extraembryonic cell types at the time of implantation, suggesting that it may play a role at this stage of development, and is subsequently expressed in all of the cells of the mid-gestation embryo with the striking exception of most of those of the developing central and peripheral nervous systems. After birth, expression of this gene ceases or is dramatically reduced in all tissues.

Amino Acid Sequence↗
PubMed1989

Selective autoimmune response to the chicken-specific structures of thyroglobulin in Obese strain chickens.

The characteristics of thyroglobulin (Tg) autoantibodies in Obese strain (OS) chickens with thyroiditis have been defined and compared with those of polyclonal antibodies to chicken Tg produced by immunizing normal chickens and a rabbit, and with mouse monoclonal antibodies (MoAb) to chicken Tg. Chicken Tg autoantibodies (aAb), when tested against Tg from 24 species all showed specificity for chicken Tg which ranged from absolute to limited although in most instances cross-reactions with Tgs of other species were either absent or at a low level. Antibodies to chicken Tg produced by immunization showed a similar limited range of cross-reactions. Four of five chTg-MoAbs were specific for chicken Tg and the fifth was almost so. In competitive experiments, the polyclonal rabbit antibody could fully inhibit binding of all chicken Tg-aAb to chicken Tg but not vice versa. It was inferred that polyclonal rabbit Tg antiserum includes antibodies to all the epitopes seen by chicken Tg-aAb and many more besides. In similar experiments with four chicken Tg-MoAbs, the binding of one chicken Tg-aAb was unaffected, and three other patterns of inhibitions were defined. The binding to chicken Tg of a fifth chicken Tg-MoAb was enhanced rather than inhibited by chicken Tg-aAb. Some but not all chicken Tg-aAb preparations could differentiate between Tgs containing different amounts of thyroxine. We conclude that the autoantibodies to Tg in OS chickens are directed in the main against determinants unique to the species. Not all the species-specific determinants are involved in the autoimmune response but the number of epitopes involved is at least four. In these respects the immune response to Tg in OS chickens resembles that in autoimmune thyroid disease in humans. The conformation of chicken Tg may be affected by combination with antibody or by the content of thyroid hormone.

Animals↗
PubMed1987

Critical role of iodination for T cell recognition of thyroglobulin in experimental murine thyroid autoimmunity.

We have used two clonotypically distinct thyroglobulin (Tg)-specific, I-Ak restricted monoclonal T cell populations to investigate the role of thyroid peroxidase-catalyzed iodination in Tg recognition by autoreactive T cells. The results showed that these T cells could recognize Tg only it it was sufficiently iodinated. Unlike normal mouse Tg, noniodinated mouse Tg was unable to induce significant thyroid lesions but could trigger the production of Tg autoantibodies. In these experiments, the importance of T cell recognition of iodination-related epitopes was emphasized by the inability of serum antibodies to distinguish Tg on the basis of iodine content, whether they were induced with normal or noniodinated Tg. Therefore, thyroid peroxidase-dependent modification of Tg would appear to be central to its recognition by autoreactive T cells and hence its capacity to induce autoimmune thyroid lesions.

Amitrole↗
PubMed1987

Novel separation method for serum immunoglobulins. Application to thyroid related antibodies.

A dye-based affinity chromatographic system using Remazol yellow GGL-Sepharose is described for the fractionation of serum immunoglobulins. Immunoglobulins are sequentially eluted from the gel columns using gradients of pH and salt with greater than 88% recovery. Specific immunoglobulin activities were identified as discrete peaks and antibodies raised against the same antigen were separated. Biological properties of antibodies were retained following chromatography. The method is applicable to both human and animal immunoglobulins.

Animals↗
PubMed1987

Human autoantibodies to thyroglobulin are directed towards a restricted number of human specific epitopes.

Significant binding of thyroglobulin (Tg) autoantibodies was restricted to primate Tg, although some sera showed weak cross-reactivities with other species at high concentrations. In contrast rabbit anti-human Tg bound to all other animals' Tg in addition to human and this was not due to crossreactions with the thyroxyl residues. Mouse antihuman Tg monoclonal antibodies (MoAb) showed at least three different patterns of cross-reactivities. Group 1 MoAb, like Tg autoantibodies, were primate specific; two out of six MoAb bound only human Tg. Group 2 MoAb also bound a few other animals' Tg in addition to human. Of the three MoAb in group 3, two reacted with most or all of eight animal Tg tested while the other bound to all eight. However the binding of thirteen out of the fourteen MoAb against human Tg including all of the primate Tg specific group 1 MoAb was not inhibited by any of the nine Tg autoantibodies. Reactions of MoAb with heat-treated human Tg varied. Examples of decreased, increased or no change in reactivity could be demonstrated. On this basis at least five or possibly six separate human-specific epitopes could be defined by group 1 MoAb. Monoclonal antibody 1D6 (group 2) was inhibited by six out of nine Tg autoantibodies at high concentrations. This MoAb, similarly to the eight Tg autosera tested, had reduced reactivity with heat treated Tg. These studies demonstrated that human Tg has immunogenic structures conserved in the Tg of many species. The protein also has, however, primate and human-specific antigenic sites but at least five or possibly six of these are not related to autoantibody binding.

Animals↗
PubMed1986

Structural differences around hormonogenic sites on thyroglobulins from different species detected by monoclonal antibodies.

Thyroxine remains attached to its synthetic site in thyroglobulin until it is released by proteolysis. Strong homology in the primary sequence surrounding thyroxine-forming residues in thyroglobulins from various species suggests a unique three-dimensional structure at hormonogenic sites. To examine this, two thyroxine-binding mouse anti-(chicken thyroglobulin) monoclonal antibodies, 1A10 and 5F6, were used as probes for this region in an enzyme-linked immunosorbent inhibition assay. The thyroxine content of thyroglobulins had a marked positive influence on the monoclonal antibody binding: when the thyroxine content of human thyroglobulin rose by 6.6-fold, cross-reactivities rose 25-fold for the 1A10 monoclonal antibody and 17.6-fold for the 5F6 monoclonal antibody. However, interspecies comparison of thyroglobulin preparations with similar thyroxine content showed lower than expected cross-reactivities for human, pig and sheep thyroglobulins when compared with chicken thyroglobulin. Only when the thyroxine content of heterologous thyroglobulin preparations was two or three times higher did the cross-reactivities equal or surpass that of chicken thyroglobulin. It is concluded that in thyroglobulin there are structural differences in the different animal species near the thyroxine-forming sites bound by these monoclonal antibodies. The known primary sequence similarity does not seem to result, therefore, in identical three-dimensional structures about this site. These differences may reflect species-specific variations in distant regions brought close as a result of chain folding to form the hormonogenic site, such as those around the donor diiodotyrosine residue or in polysaccharide structures. These monoclonal antibodies provide information about the structure of thyroglobulin, which cannot be obtained from knowledge of the amino acid sequence alone.

Animals↗
PubMed1985

Enterobiasis among schoolchildren in Macao.

The prevalence of enterobiasis was investigated among 2,195 children in kindergarten and grade one of 12 Macao Catholic schools by a single modified Scotch tape swab. The overall infection rate was 31.5%; it ranged from 15.2% to 63.3% among schools and was higher in grade one. The prevalence was independent of sex but increased with age to a peak at 7 years; it was higher among children of lower social class and those born in Mainland China. The infection was more prevalent in the poor and congested parts of the city. The educational level of parents was a critical factor in the eradication of enterobiasis. The prevalence rate was not associated with the employment status of mother, family size, and sibling size.

Adolescent↗
PubMed1980

Properties of acyl-CoA:cholesterol O-acyltransferase in aortic microsomes from atherosclerotic rabbits.

Acyl-CoA:cholesterol O-acyltransferase (EC 2.3.1.26) was in microsomal fractions from atherosclerotic rabbit aortic tissue. Activity was increased over 70-fold following 8-11 weeks of cholesterol feeding. Comparison of the lipid composition of aortic microsomal fractions from control and cholesterol-fed animals showed a 2-fold increase in the molar ratio of unesterified cholesterol to phospholipid in the cholesterol-fed group, although no change in phospholipid content or composition was found. Aortic microsomes were fractionated by sucrose density gradient centrifugation. Acyl-CoA:cholesterol O-acyltransferase was localized in fractions containing neutral alpha-glucoside activity but was clearly separated from 5'-nucleotidase activity. The cholesteryl ester formed during in vitro incubation of incubations of microsomes with either [1-14C]-oleoyl CoA or [7-3H]cholesterol was localized in the same region of the density gradient as acyl-CoA:cholesterol O-acyltransferase. The studies indicate that the increased acyl-CoA:cholesterol O-acyltransferase activity found in cells from aortic atherosclerotic lesions is due to both an increased amount of enzyme and to an expanded pool of microsomal cholesterol which is available for esterification.

Acyltransferases↗