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Biomedical subjects

S Y Chan

Publications and source records attributed to S Y Chan.

At least 109 records · Page 6Linked to original sources
PubMed1997

Genomic diversity and evolution of papillomaviruses in rhesus monkeys.

We are studying the diversity of and relationships among papillomaviruses (PVs) to understand the modes and timescales of PV evolution and in the hope of finding animal PVs that may serve as model systems for disease caused by human PVs (HPVs). Toward this goal, we have examined 326 genital samples from rhesus monkeys and long-tailed macaques with a PCR protocol optimized for detecting genital HPV types. In 28 of the rhesus monkey samples, we found amplicons derived from 12 different and novel PV genomes, RhPV-a to RhPV-m, with the likely taxonomic status of "type." The frequency with which novel RhPVs were detected suggests that rhesus monkeys may play host to PVs with a diversity similar to that of humans. In phylogenetic trees, all 12 of the different RhPVs and the previously described type RhPV-1 were members of the genital HPV supergroup and formed three minor branches distinct from the 11 branches formed by genital HPVs. We also identified a novel PV amplicon, MfPV-a, from a long-tailed macaque, a species belonging to the same genus as rhesus monkeys. MfPV-a turned out to be a close relative of five RhPVs. It appears that the evolution of primate lineages leading to the genus Macaca and to humans created transmission barriers for PVs, resulting in viral evolution closely linked to the host. Additional support for the linked-evolution hypothesis comes from considering the phylogenetic association of two other ape and monkey PVs with the genital HPVs, the supergroup formed by at least seven ungulate PVs, and the isolated phylogenetic position of the only known bird PV.

Amino Acid Sequence↗
PubMed1997

Novel methodology for echocardiographic quantification of cardiac shape.

BACKGROUND: Left ventricular (LV) shape is a major determinant of cardiac physiology with important prognostic implications. Current techniques are limited in their ability to characterize shape. Regional curvature analysis is a recently developed method that is free of idealized shape assumptions and is applicable globally or regionally. OBJECTIVE: To measure the change in regional curvature from diastole to systole to determine whether modifications of this methodology can be applied to study LV shape noninvasively, and to compare this method with other shape analysis methods. ANIMALS: Seventeen normal dogs underwent transthoracic echocardiography. LV dimensions were measured at end-diastole and end-systole. LV endocardial outlines were traced from apical four-chamber views. LV short to long axis (D/L) ratios and eccentricity index (E) were calculated. Regional curvatures were determined using customized software. Reproducibility of regional curvature was also determined. MAIN RESULTS: LV regional curvature values were consistent among animals at diastole and systole in all areas. Regional curvature showed divergence in different areas. D/L ratios showed a 7% decrease from diastole to systole, whereas E demonstrated a 10% increase. However, regional curvature exhibited a 39% change, suggesting that this methodology is more sensitive. Duplicate curvature values from same or different cardiac cycles were highly reproducible. CONCLUSIONS: Quantitative regional curvature analysis can be applied with echocardiography to study LV shape. This methodology is more sensitive than current methods, is reproducible and may be applicable to the noninvasive study of shape changes in cardiac disease.

Analysis of Variance↗
PubMed1996

Identification of mutations in seven Chinese patients with X-linked chronic granulomatous disease.

X-linked chronic granulomatous disease (CGD) is due to mutations in the gp91phox gene on Xp21.1. Studies in white and Japanese X-linked CGD patients have shown mutations in nearly every exon. We studied the molecular defect of seven Chinese patients with X-linked CGD from six unrelated families. Mutations were located by single-strand conformation polymorphism and then defined by sequence analysis. The mutations were two different amino acid substitutions, a nonsense mutation, an in-frame trinucleotide deletion, a single A insertion causing a frameshift, and a premature stop. Lastly, a rare splice site mutation caused by G to A transition at the terminal nucleotide of exon 3, resulting in the skipping of exon 3, was found. The possible effects of these mutations on protein structure-function or splicing were discussed. Together with previous reports, the A insertion in the run of six As from nucleotide 749 to 754 and the G to A transition at the terminal position of exon 3 may be mutation hotspots of the gp91phox gene. The extreme heterogeneous mutations found in our patients suggest the absence of ethnic group-specific mutation.

Amino Acid Sequence↗
PubMed1996

IL-12 antagonism induces T helper 2 responses, yet exacerbates cardiac allograft rejection. Evidence against a dominant protective role for T helper 2 cytokines in alloimmunity.

IL-12 promotes Th1 development and inhibits the generation of Th2 by inducing IFN-gamma production. In several experimental models, Th2 are preferentially induced in the absence of IL-12. It was proposed that the preferential induction of Th2 by IL-12 antagonism would inhibit Th1-driven rejection responses, thereby promoting allograft acceptance. To test this possibility, mouse cardiac allograft recipients were treated with either anti-IL-12 Abs, or with the IL-12 receptor antagonist p40 homodimer. Unmodified rejection is characterized by a Th1-dominated response, with Th2 cytokines being absent or only weakly expressed within the allograft. Though both forms of IL-12 antagonism induced Th2 cytokine expression within the allograft, these treatments surprisingly exacerbated graft rejection relative to control animals. Interestingly, IL-12 antagonism did not inhibit IFN-gamma gene expression or in vivo sensitization of IFN-gamma-producing cells. Similar observations were made when IL-12 p40 knockout mice were used as allograft donors and recipients, verifying that IL-12 was not required for Th1 development. Further, IL-12 antagonism was associated with strong expression of p40 and weak expression of p35 within the graft. Neither p35 nor p40 mRNAs were detectable in control allografts. These data indicate that while IL-12 antagonism does induce Th2 cytokine expression within cardiac allografts, Th2 cytokines do not play a dominant protective role in the rejection process. Further, the Th2-inducing activity of IL-12 antagonism is not related to decreased IFN-gamma production, but may reflect altered regulation of IL-12 itself.

Animals↗
PubMed1996

Allogeneic class I MHC requirement for alloantigen-reactive helper T-lymphocyte responses in vivo. Evidence for indirect presentation of alloantigen.

The mechanisms by which host T cells recognize transplant-associated alloantigens in vivo have not been established. Two alloantigen presentation pathways may be used: (1) allogeneic class I and class II MHC molecules may be recognized directly by host CD8+ and CD4+ cells, respectively, or (2) allogeneic MHC molecules may be processed as foreign peptide and presented by host antigen-presenting cells to CD4+ cells in the context of self class II proteins. In this study, the sponge matrix allograft model was used to examine the relative contributions of these alloantigen presentation pathways to CD4+ T-cell activation in vivo. Limiting dilution analysis was used to quantify the localization of interleukin-2-producing helper T lymphocytes (HTL) following implantation of sponge allografts. Allografts either were disparate at both class I and class 11, or were derived from beta2-microglobulin knockout (beta2M-/-) mice, which express class II but are deficient in class I. Two measures of in vivo HTL function were monitored: (1) the accumulation of HTL within the allograft (a process that is dependent upon antigen-driven cytokine production), and (2) the development of cytolytic alloantibodies. After implantation of sponge allografts expressing both class I and class II, HTL were readily detectable in the allograft, and cytolytic alloantibodies were present in the serum. When mice were implanted with beta2M-/- sponge allografts, HTL failed to infiltrate these class I-deficient allografts, and alloantibodies were not detectable in the sera of recipients of beta2M-/- sponge allografts. This in vivo requirement for class I expression was not reflected by traditional in vitro measures of HTL function; cells obtained from lymphoid tissues mounted a mixed lymphocyte response and produced interleukin-2 when stimulated with beta2M-/- splenocytes in vitro. One possible interpretation of these data is that in vivo HTL functions are dependent upon the presence of class I-reactive CD8+ T cells. However, HTL readily infiltrated grafts expressing both class I and class II when recipients depleted of CD8+ T cells, and alloantibodies were produced. These observations support the idea that indirect presentation of allogeneic class I molecules plays a critical role in regulating CD4+ HTL functions associated with allograft rejection in vivo.

Animals↗
PubMed1995

Human papillomaviruses in 91 oral cancers from Indian betel quid chewers--high prevalence and multiplicity of infections.

India has one of the world's highest incidences of oral cancer. The habit of chewing betel quid is widespread and is suspected to play a role in the etiology of this disease. Studies in many other countries have also pointed to a role for human papilloma-viruses (HPVs) in the etiology of some oral cancers. In this study we analyzed biopsies from 91 Indian oral cancer patients, most of whom were betel quid chewers, by PCR amplification and direct DNA sequencing. HPV DNA was detected in 74% of these lesions, of which 41% had multiple HPV infections. Among the lesions from different oral sites, lesions of the tongue had the highest rate (9 of 11) of HPV infection. These HPV prevalences are among the highest ever reported in oral cancers. As to individual HPV types, prevalences of HPV-6, HPV-11, HPV-16 and HPV-18 were 13%, 20%, 42% and 47%, respectively. No additional known or novel HPV types were detected. To understand the unexpectedly high prevalences of the "low-risk" types HPV-6 and HPV-11, we compared the subtypes and variants that were found in oral cancers against those from benign genital warts from the same patient population but found no differences. The high prevalence of HPV in the oral cancers of these Indian patients suggests that viral infection is an important etiological component, with betel quid probably causing additional mutagenic steps in the carcinogenic process.

Areca↗
PubMed1995

In vivo depletion of CD8+ T cells results in Th2 cytokine production and alternate mechanisms of allograft rejection.

A current hypothesis states that Th1 cytokines promote allograft rejection and that Th2 cytokines promote graft acceptance. We present data that question the tolerogenic activity of Th2 cytokines, and we suggest that Th2 cytokines may evoke allograft rejection by recruitment of alternate effector mechanisms. Unmodified rejection of mouse heterotopic cardiac allografts is associated with the accumulation of large numbers of donor-reactive CD8+ CTL within the allograft, which is indicative of a Th1-driven cellular response. However, when recipients are depleted of CD8+ CTL, rejection still occurs and is associated with an aggressive cellular infiltrate rich in eosinophils, large mononuclear cells, and fibroblast-like cells. Eosinophils, which are responsive to the Th2 cytokines IL-4 and IL-5, are not present in unmodified rejecting allografts. Differential production of Th1 versus Th2 cytokines was further suggested by altered levels of IgG2a (promoted by IFN gamma) and IgG1 (promoted by IL-4) alloantibody in the sera of these mice; IgG2a dominated the alloantibody response in unmodified allograft recipients, whereas IgG1 levels increased in recipients depleted of CD8+ CTL. Altered intragraft cytokine gene expression was verified by RT-PCR; Th1 (IL-2, IFN gamma), but not Th2 (IL-4, IL-5, IL-10), cytokine mRNAs were readily detectable in the allografts of unmodified recipients. In contrast, both Th1 and Th2 cytokine genes were expressed in the allografts of mice depleted of CD8+ CTL. These data suggest that donor-reactive CD8+ CTL inhibit intragraft production of Th2 cytokines, thereby promoting a Th1 dominated-rejection response. Elimination of CD8+ cells allows Th2 cytokine production, which may have deleterious, rather than protective, effects.

Animals↗
PubMed1995

In situ detection of Epstein-Barr virus in non-small cell lung carcinomas.

Epstein-Barr virus (EBV) is strongly associated with nasopharyngeal carcinoma and lymphoepithelioma-like carcinomas (LELC) of foregut-derived organs. Recently this group of EBV-associated carcinomas has been expanded by the identification of the virus in conventional adenocarcinomas of the stomach. In situ hybridization (ISH) using a sensitive digoxigenin-labelled EBER RNA probe was performed on 167 consecutive unselected primary non-small cell lung carcinomas, to determine the frequency of EBV association in these tumours. Nine cases (5.4 per cent) showed strong EBER signals in the tumour cell nuclei. By immunohistochemistry, four of the EBER-positive tumours showed patchy expression of the viral latent membrane protein (LMP-1) and none showed any expression of the EBV nuclear antigen 2 (EBNA2). Morphologically, all the positive tumours were LELC, whereas no conventional type of non-small cell lung carcinoma showed EBV association. The LELC presented a morphological spectrum from undifferentiated to squamoid or glandular differentiation. The patients showed a male to female ratio of 8:1. The mean age at presentation was 48 years. Smoking was not a risk factor. All patients were alive at follow-up periods of 23-52 months. Southern blot analysis performed on eight of the nine positive tumours showed a clonal episomal form of EBV, suggesting the clonal expansion of an infected tumour cell early in oncogenesis. These characteristics of the EBV-associated lung tumours justify their consideration as a distinct clinicopathological entity.

Adult↗
PubMed1995

Can the Hospital Anxiety and Depression (HAD) Scale be used on Chinese elderly in general practice?

A study was carried out in a general practice in Hong Kong to find out if the Hospital Anxiety and Depression (HAD) Scale could be used to detect psychological problems in Chinese elderly. The HAD Scale was translated into Cantonese and administered by an interviewer to 298 Chinese aged 60 or above before their doctor consultations. The acceptance rate of the Scale was 96% and each interview took only 5-10 min to complete. All 298 elderly understood and completed the HAD Scale. Validation of the results of the HAD Scale by the Clinical Interview Schedule (CIS) was done on a random sample of 100 elderly. Relative operating characteristic (ROC) analysis showed that the optimal cut-off points of the HAD Scale was a depression score of 6 and an anxiety score of 3. The sensitivity was 80%, specificity was 90%, OMR (overall misclassification rate) was 12%, positive predictive value was 67% and negative predictive value was 95%. Thirty-six per cent of the elderly had scores above these cut-off points. More females than males had high anxiety scores. Nearly half of those with positive HAD scores were not known to have any psychological illness. The HAD Scale has great potential to be used as a screening instrument for psychological illnesses in Cantonese-speaking Chinese elderly all over the world.

Age Factors↗
PubMed1995

Epstein-Barr virus is present in a wide histological spectrum of sinonasal carcinomas.

Nasopharyngeal carcinomas, a common occurrence in Southern Chinese people, shows a strong association with Epstein-Barr virus (EBV); in the same population, sinonasal carcinomas are distinctly rare. Although most nasopharyngeal carcinomas are lymphoepitheliomas, sinonasal carcinomas have a wide morphological spectrum. We studied the clinicopathological features and EBV status of 29 sinonasal carcinomas from Hong Kong Chinese patients. By in situ hybridization using antisense Epstein-Barr virus early RNA (EBER) probe, seven tumors were shown to be strongly positive for the EBV RNA. They displayed a wide morphological spectrum, including one cylindric cell carcinoma, one intestinal type adenocarcinoma, four nonkeratinizing squamous cell carcinomas, and one undifferentiated carcinoma. All were from elderly subjects (mean age, 67), including six men and one woman. Three of these seven patients had complete remission after radiotherapy with a median follow-up period of 29 months. In two cases, EBV latent membrane protein-1 was expressed. Detection of the virus in a number of histological subtypes, including cylindric cell carcinoma and adenocarcinoma, suggests that EBV may play a role in the pathogenesis of a diverse spectrum of carcinomas.

Aged↗
PubMed1995

Mannose-binding protein in preterm infants: developmental profile and clinical significance.

The aim of this study was to determine the developmental profile of mannose-binding protein (MBP) in preterm infants. MBP was measured in 885 longitudinally collected serum samples from 168 preterm infants, and 63 were genotyped with respect to the codon 54 mutation in the MBP gene. MBP level/codon 54 genotyping were also determined on the cord blood of 146/123 term infants and 138/123 adults, respectively. The best cut-off values of MBP for dividing preterm, term infants and adults into 'low' and 'high' MBP groups were 400 ng/ml (55 low, 113 high), 700 ng/ml (35 low, 111 high) and 750 ng/ml (33 low, 105 high), respectively, by achieving the least number of misclassifications according to the codon 54 mutation. The relative risk of the 'low' groups for presence of the codon 54 mutation compared with 'high' groups were 42.4, 67.9 and 22.9 for preterm, term infants and adults, respectively (P < 0.00001). The gestational age and birth weight of the 'low' (n = 55) and 'high' (n = 113) MBP groups of the 168 preterm infants were 29.5 +/- 2.8 weeks, 30.5 +/- 2.8 weeks (P = 0.03) and 1230 +/- 317 g, 1277 +/- 289 g (P = 0.35), respectively. The mean MBP levels of these two groups of preterm infants were different (P < 0.001) at all ages measured. As a whole group, the MBP level rose from a mean of 500 ng/ml at 25 weeks gestation to 1700 ng/ml at 20 weeks post full-term. The mortality rates of 'low' and 'high' MBP groups of preterm infants were 22% and 12%, respectively (P = 0.113). This difference in mortality was due to gestational age and birth weight standard deviation score (SDS) after adjusting for length of gestation and gender (P = 0.0001) rather than to low MBP levels (P = 0.65). MBP levels were not related to birthweight SDS score (P = 0.26). The mean +/- s.d. MBP levels for preterm, term infants and adults without the codon 54 mutation were 1225 +/- 701 ng/ml (n = 45), 2064 +/- 829 ng/ml (n = 88) and 2473 +/- 1395 ng/ml (n = 95), respectively; the corresponding values for those with the codon 54 mutation were 130 +/- 275 ng/ml (n = 18), 533 +/- 665 ng/ml (n = 35) and 330 +/- 225 ng/ml (n = 28), respectively. Intra-uterine growth retardation in preterm infants does not influence MBP levels. For those without the codon 54 mutation, there is a significant difference in MBP level between the three age groups. For those with the codon 54 mutation, there is a significant difference between preterm and term infants, but not between term infants and adults. We conclude that there is a maturation in MBP levels for preterm infants, and that a moderately low MBP phenotype does not affect survival. We cannot exclude an effect of profoundly reduced MBP levels (characteristic of individuals homozygous for the codon 54 mutation), since no such preterm infant was identified in this study.

Adult↗
PubMed1995

Variation of human papillomavirus type 6 (HPV-6) and HPV-11 genomes sampled throughout the world.

We examined the genomic diversity of human papillomavirus type 6 (HPV-6) and HPV-11 isolates from different parts of the world by comparing the nucleotide sequences of part of the long control region of three reference clones and 62 HPV-6 and 40 HPV-11 isolates from Africa, Europe, Asia, and North and South America. The genomic sequence of the HPV-6b reference type had to be amended by inclusion of a 94-bp segment, which is also present with minor differences in HPV-6a. Aside from two small inserts typical of all variants related to HPV-6a and three inserts found in HPV-11 variants, no major alterations to the size of the long control regions of these viruses were observed. This corrects the previous impression that these two HPV types are highly polymorphic. Altogether, 19 HPV-6 and 10 HPV-11 variant genomes could be distinguished, and most of the differences were due to point substitutions. The variants of either type were continuously connected in phylogenetic trees rather than clustered separately into subtype groups. Thirteen mutations, namely, the two HPV-6a inserts and 11 substitutions in HPV-6 or HPV-11 variants, reduced the dissimilarity between the types, but they bridged only a small fraction of the genetic distance between the two types. Genomes more obviously intermediate between HPV-6 and HPV-11 were not found and probably do not exist any more. A single HPV-11 variant was found in Africa, but otherwise, no significant correlations of HPV-6 or HPV-11 variants with geography or ethnicity of the patient cohort were found. Functional analysis of diverse enhancer variants showed activities that differed two-to threefold, and it must be considered that transcriptional differences may alter the biology or pathology of these viruses. Similar variants were found in lesions from anatomically different sites and in both benign and malignant lesions.

Base Sequence↗