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Biomedical subjects

A C Chan

Publications and source records attributed to A C Chan.

At least 163 records · Page 9Linked to original sources
PubMed1995

Evidence for lytic infection by Epstein-Barr virus in mucosal lymphocytes instead of nasopharyngeal epithelial cells in normal individuals.

Normal nasopharyngeal tissues from 23 individuals who died of causes unrelated to the upper respiratory system and had no evidence of Epstein-Barr virus (EBV)-related diseases were studied using in situ hybridisation (ISH) and immunohistochemistry for the detection of EBV RNA and expression of EBV proteins, respectively. ISH using 35S-labelled riboprobe for EBV EBER RNA showed occasional to a few EBER+ lymphocytes in the stroma of nasopharyngeal mucosa in 14/16 cases with available paraffin-embedded tissues. In addition, very rare intraepithelial EBER+ lymphocytes were also detected in 3/16 cases. However, in none of these cases was EBER detected in the epithelial cells. Similar results were obtained using a nonradioactive ISH method for EBER (Dako). In 3/23 cases, immunostaining using monoclonal antibodies for EBV proteins on cryostat sections showed occasional cells in the stroma expressing EBV nuclear antigen 2 (EBNA2), latent membrane protein-1 (LMP), and switch protein encoded by BZLF1 gene (ZEBRA) in two cases and only very rare LMP+ and ZEBRA+ cells in one other case. Double immunostaining combining alkaline phosphatase anti-alkaline phosphatase (APAAP) for CD markers and indirect immunofluorescence for LMP showed that the LMP+ cells were either CD19+ or less frequently CD3+, but none were CD68+. These results show that both B and T lymphocytes harbouring EBV can be found in the normal nasopharyngeal tissues. Interestingly, EBV proteins associated with lytic viral replication--diffuse early antigen (EA-D), viral capsid antigen (VCA), or membrane antigen (MA)--were also detected in rare cells in the stroma in one case, and in another case only one MA+ cell was detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Reconstitution of Syk function by the ZAP-70 protein tyrosine kinase.

ZAP-70 and Syk are PTKs required for TCR and BCR function, respectively. Loss of the Syk PTK results in a nonfunctional BCR. We provide evidence here that ZAP-70 and Syk are functionally homologous in antigen receptor signaling by demonstrating that expression of ZAP-70 in Syk- B cells reconstitutes BCR function. Reconstitution required the presence of functional Src homology 2 (SH2) and catalytic domains of ZAP-70. Thus, drug targeting of a single SH2 domain within ZAP-70 should be sufficient to inhibit hematopoietic antigen receptor function. In addition, we demonstrate that both ZAP-70 and Syk can bind directly to the phosphorylated Ig alpha and Ig beta subunits with affinities comparable to their binding to the TCR CD3 epsilon subunit. These data suggest that ZAP-70 and Syk are comparable in their abilities to mediate hematopoietic antigen receptor signaling.

Amino Acid Sequence↗
PubMed1995

Expression of p53 and its relationship with human papillomavirus in penile carcinomas.

We studied p53 over-expression in a series of 42 primary penile carcinomas (seven verrucous carcinomas, 14 well-differentiated, 15 moderately-differentiated and six poorly-differentiated squamous cell carcinomas) from Chinese patients using the p53 protein specific mouse monoclonal antibody DO-7 on paraffin sections. p53 protein was detected in 40% (17 cases) of the tumours. The p53 staining was not observed in the penile warts (n = 6) and verrucous carcinomas (n = 7). Positive p53 staining was identified only in the less differentiated tumour cells in the periphery of the tumour cell nests in all the cases. The non-invasive dysplastic epithelium next to the tumours could also be positive for p53 protein (three out of 10 cases in which the dysplastic epithelium adjacent to the tumour was adequately sampled). Furthermore, 100% of the human papillomavirus (HPV)-positive cases showed positive p53 staining. It is concluded that p53 over-expression is present in penile squamous cell carcinomas and adjacent non-invasive tumour cells. An inverse correlation between HPV and p53 gene mutation is not observed in penile cancers.

Adult↗
PubMed1995

Binding of ZAP-70 to phosphorylated T-cell receptor zeta and eta enhances its autophosphorylation and generates specific binding sites for SH2 domain-containing proteins.

ZAP-70 is a protein tyrosine kinase thought to play a critical role in T-cell receptor (TCR) signal transduction. During T-cell activation, ZAP-70 binds to a conserved signalling motif known as the immune receptor tyrosine activating motif (ITAM) and becomes tyrosine phosphorylated. To determine whether binding of ZAP-70 to the phosphorylated ITAM was able to activate its kinase activity, we measured the kinase activity of ZAP-70 both when it was bound and when it was unbound to phosphorylated TCR subunits. The ability of ZAP-70 to phosphorylate itself, but not exogenous substrates, was enhanced when it was bound to the tyrosine-phosphorylated TCR zeta and eta chains or to a construct that contained duplicated epsilon ITAMs. No enhanced ZAP-70 autophosphorylation was noted when it was bound to tyrosine-phosphorylated CD3 gamma or epsilon. In addition, autophosphorylation of ZAP-70 when bound to zeta or eta resulted in the generation of multiple distinct ZAP-70 phosphorylated tyrosine residues which had the capacity to bind the SH2 domains of fyn, lck, GAP, and abl. As the effect was noted only when ZAP-70 was bound to TCR subunits containing multiple ITAMs, we propose that one of the roles of the tandem ITAMs is to facilitate the autophosphorylation of ZAP-70. Tyrosine-phosphorylated ZAP-70 then mediates downstream signalling by recruiting SH2 domain-containing signalling proteins.

Amino Acid Sequence↗
PubMed1995

Peliosis of the spleen: possible association with chronic renal failure and erythropoietin therapy.

Splenic peliosis was identified at necropsy in a 62-year-old woman receiving continuous ambulatory peritoneal dialysis for end-stage renal failure, and erythropoietin therapy for uraemia and anaemia. The immediate cause of death was arrhythmia related to ischaemic heart disease, following an episode of intramuscular haematoma (secondary to platelet dysfunction). The unusual association between peliosis and renal failure, and possibly erythropoietin therapy, is discussed.

Anemia↗
PubMed1994

Human severe combined immunodeficiency due to a defect in ZAP-70, a T cell tyrosine kinase.

A homozygous mutation in the kinase domain of ZAP-70, a T cell receptor-associated protein tyrosine kinase, produced a distinctive form of human severe combined immunodeficiency. Manifestations of this disorder included profound immunodeficiency, absence of peripheral CD8+ T cells, and abundant peripheral CD4+ T cells that were refractory to T cell receptor-mediated activation. These findings demonstrate that ZAP-70 is essential for human T cell function and suggest that CD4+ and CD8+ T cells depend on different intracellular signaling pathways to support their development or survival.

Alleles↗
PubMed1994

ZAP-70 deficiency in an autosomal recessive form of severe combined immunodeficiency.

Protein tyrosine kinases (PTKs) play an integral role in T cell activation and differentiation. Defects in the Src-family PTKs in mice and in T cell lines have resulted in variable defects in thymic development and in T cell antigen receptor (TCR) signal transduction. Here, three siblings are described with an autosomal recessive form of severe combined immunodeficiency disease (SCID) in which ZAP-70, a non-Src PTK, is absent as a result of mutations in the ZAP-70 gene. This absence is associated with defects in TCR signal transduction, suggesting an important functional role for ZAP-70.

Amino Acid Sequence↗
PubMed1994

Differential expression of ZAP-70 and Syk protein tyrosine kinases, and the role of this family of protein tyrosine kinases in TCR signaling.

TCR stimulation results in the tyrosine phosphorylation of a number of cellular substrates. We have recently identified a 70-kDa protein tyrosine kinase, ZAP-70, which associates with the human TCR zeta-chain after TCR stimulation. We report here the isolation and sequence of a cDNA clone that encodes murine ZAP-70. Murine and human ZAP-70 share 93% amino acid identity and are homologous to the 72-kDa protein tyrosine kinase Syk. Syk has been implicated in the signal transduction pathways of the B cell membrane Ig and high affinity IgE receptors, Fc epsilon RI. In addition, we examined the tissue distribution of ZAP-70 and Syk in human and murine thymocyte subsets, B cells, and peripheral T cell subsets. ZAP-70 protein is expressed in all major thymocyte populations, with the level of expression being comparable to that found in both CD4+ and CD8+ peripheral T cells. Although Syk protein is also present in all thymocyte subsets, expression of Syk protein is down-regulated threefold to fourfold in peripheral T cells. In contrast to ZAP-70, expression of Syk is 12- to 15-fold higher in peripheral B cells when compared with peripheral T cells. In addition, whereas T cell stimulation results in down-regulation of Lck, no significant change in ZAP-70 or Syk protein is detected. Finally, we provide evidence that both ZAP-70 and Syk can associate with the TCR after TCR stimulation. With the use of a heterologous expression system, we show that, like ZAP-70, Syk is dependent upon a Src-family protein tyrosine kinase for association with the phosphorylated zeta-chain. Thus, the differential expression of these kinases suggests the possibility of different roles for ZAP-70 and Syk in TCR signaling and thymic development.

Amino Acid Sequence↗
PubMed1994

Vitamin E suppresses diacylglycerol (DAG) level in thrombin-stimulated endothelial cells through an increase of DAG kinase activity.

The present study has examined the role of vitamin E, a natural lipid antioxidant, in the production of diacylglycerol (DAG) and phosphatidic acid (PA) in thrombin-stimulated human endothelial cells. Cells were labelled with [3H]myristate and the incorporation and distribution of [3H]myristate into cellular lipids was not affected by vitamin E. However, in response to thrombin stimulation, considerably more PA and less DAG were formed in cells enriched with vitamin E. The time-course of thrombin stimulation indicated that vitamin E attenuated the accumulation of sustained DAG levels with a concomitant increase in PA. Direct determination of DAG mass further confirmed that vitamin E suppresses the accumulation of DAG induced by thrombin. In the presence of ethanol, the formation of [3H]phosphatidylethanol (PEt) in [3H]myristate-labelled cells stimulated by thrombin was unaffected by vitamin E enrichment. DL-Propranolol, a PA phosphohydrolase inhibitor, caused an accumulation of PA, without affecting DAG formation in either vitamin E-treated and untreated cells. This indicated that the increase in PA and decrease in DAG in vitamin E-treated cells was not due to a stimulation of phospholipase D or an inhibition of PA phosphohydrolase. Determination of inositol phosphates formation in response to thrombin showed that the change of DAG levels elicited by vitamin E was independent of phospholipase C-induced hydrolysis of inositol phospholipids. In contrast, analysis of DAG kinase activity revealed that vitamin E enrichment enhanced the activity of the enzyme in both basal and thrombin-stimulated cells. Taken together, these data indicated that vitamin E caused an increased conversion of DAG to PA by activating DAG kinase activity without causing any change in the activities of phospholipase D, PA phosphohydrolase or phospholipase C.

Cells, Cultured↗
PubMed1994

Molecular cloning of human Syk. A B cell protein-tyrosine kinase associated with the surface immunoglobulin M-B cell receptor complex.

B cell antigen receptors are multicomponent complexes consisting of the surface immunoglobulin and accessory molecules with associating protein-tyrosine kinases. A spleen tyrosine kinase, Syk, in porcine B cells and a 72-kDa protein-tyrosine kinase, PTK72, in murine B cells associate with the B cell antigen receptor. Herein, we report the isolation of a full-length cDNA encoding the human homologue of Syk. This cDNA predicted a polypeptide consisting of two NH2-terminal SH2 domains and a COOH-terminal tyrosine kinase domain. Syk is highly conserved between human and swine and is homologous to the T cell-associated protein-tyrosine kinase ZAP-70. Both Syk mRNA and protein were detected in cells derived from multiple hematopoietic lineages. Within the B cell compartment, Syk was expressed from pro-B cells to plasma cells. In vitro kinase assays conducted on the human Syk protein isolated from B cells revealed the presence of autophosphorylation activity on Syk tyrosine residues. Tyrosine phosphorylation of Syk associating with the B cell receptor complex in human was augmented rapidly after surface immunoglobulin cross-linking. The human SYK locus was mapped to chromosome 9 at band q22.

Amino Acid Sequence↗
PubMed1994

Sequential interactions of the TCR with two distinct cytoplasmic tyrosine kinases.

The T cell antigen receptor (TCR) initiates signals by interacting with cytoplasmic protein tyrosine kinases (PTKs) through a 17-residue sequence motif [called the antigen recognition activation motif (ARAM)] that is contained in the TCR zeta and CD3 chains. TCR stimulation induces the tyrosine phosphorylation of several cellular substrates, including the ARAMs. Lck kinase activity is required for phosphorylation of two conserved tyrosine residues in an ARAM. This phosphorylation leads to the recruitment of a second cytoplasmic PTK, ZAP-70, through both of the ZAP-70 Src homology 2 domains and its phosphorylation. Thus, TCR signal transduction is initiated by the sequential interaction of two PTKs with TCR ARAMs.

Amino Acid Sequence↗
PubMed1994

Vitamin E enhances the acylation of 1-O-alkyl-sn-glycero-3-phosphocholine in human endothelial cells.

1-O-Alkyl-2-acyl-sn-glycero-3-phosphocholine (alkylacyl-GPC) is the precursor of platelet-activating factor. It is formed via the CoA-independent transacylase reaction, which transfers the polyenoyl acyl group from the sn-2 position of a diacyl phospholipid to the sn-2 position of 1-O-alkyl-sn-glycero-3-phosphocholine (alkyl-GPC). We have reported previously that vitamin E alters phospholipid turnover in the endothelial cells by increasing arachidonic acid release and prostacyclin synthesis. In the present study, the role of vitamin E in the formation of alkylacyl-GPC was investigated. Incubation of endothelial cells with vitamin E resulted in an increase in the formation of [3H]alkylacyl-GPC from [3H]alkyl-GPC. The effect of vitamin E was dose-dependent at concentrations below 23 microM. However, vitamin E did not have a direct effect on the transacylase activity. When endothelial cells were incubated with vitamin E, the CoA-independent transacylase activity in the cell homogenate was found to be enhanced. Kinetic analysis of the transacylase activity in the pre-incubated cells showed that the enhancement of enzyme activity was at the enzyme-substrate level. When endothelial cells were incubated with vitamin E analogues (Trolox, tocol and tocopherol acetate), only limited enhancement of the transacylation process was detected. It is clear that vitamin E enhanced the synthesis of alkylacyl-GPC from alkyl-GPC in a very specific manner by an indirect stimulation of the CoA-independent transacylase activity. The regulation by vitamin E of the formation of alkylacyl-GPC may mediate the transfer of arachidonate from the diacyl phospholipid pool into the ether-linked phospholipid pool.

Acetyl-CoA C-Acyltransferase↗
PubMed1994

Early results of laparoscopic intraperitoneal onlay mesh repair for inguinal hernia.

Over a 15-month period, 39 patients (37 men) of mean age 52 years underwent laparoscopic inguinal hernia repair. Seven patients had bilateral hernia. Forty-six hernias (33 indirect, five direct, eight both direct and indirect) were repaired. A piece of polypropylene mesh measuring 8 x 10 cm was used to cover the direct and indirect spaces with an endoscopic multifeed hernia stapler. The mean operating time for unilateral and bilateral repair was 49 and 63 min respectively (range 25-90 min). One-third of patients required no postoperative analgesia and only seven had more than one injection of pethidine. The median postoperative stay was 1 (range 1-3) days. The mean period to resumption of daily activities was 7 (range 4-21) days. Three patients complained of paraesthesia of the lateral aspect of the thigh and one developed a hydrocele. Two recurrences were noted on follow-up at 3 months.

Adolescent↗
PubMed1994

Miliary tuberculosis with splenic rupture: a fatal case with hemophagocytic syndrome and possible association with long standing sarcoidosis.

A fatal case of miliary tuberculosis complicated by splenic rupture and reactive hemophagocytic syndrome is presented. A 42 yr old Indian patient with a 7 yr history of sarcoidosis developed miliary tuberculosis and hemophagocytic syndrome after steroid therapy. A ruptured enlarged spleen with hemoperitoneum was detected at autopsy. This case highlights the need to consider the occurrence of tuberculosis in patients with sarcoidosis, especially after steroid therapy. Yellow bodies (Hamazaki-Wesenberg bodies), commonly but not exclusively found in sarcoidosis, were identified within the retroperitoneal lymph nodes in this case.

Adult↗
PubMed1994

Evaluation of a histogenetic classification for thymic epithelial tumours.

We reviewed 87 thymic epithelial tumours from Chinese patients and typed them according to the Marino and Müller-Hermelink classification as updated by Kirschner and Müller-Hermelink in 1989. Related categories were grouped for statistical analyses: group 1, medullary thymoma and mixed thymoma; group 2, cortical predominant thymoma; group 3, cortical thymoma and well-differentiated thymic carcinoma; group 4, other thymic carcinomas; and group 5, unclassified. Group 3 tumours were more frequently associated with the myasthenia gravis syndrome compared with group 1 tumours (P = 0.001). They also presented at a more advanced stage. Groups 1 and 2 showed an excellent prognosis (100% survival at 10 years). The 10-year survival for groups 3 and 4 patients was 40% and 30% respectively. Pure medullary thymoma made up a higher proportion of our cases (10.3%) than those of a similar Caucasian study (5.3%). The eight thymic carcinomas (group 4) included two thymic lymphoepitheliomas. We conclude that the histogenetic classification evaluated shows a clear correlation with prognosis and clinical features, even when tested on separate geographic groups, where pathogenetic factors may be different. A common approach to classification of thymic epithelial tumours would greatly facilitate future studies on these possible differences.

Adult↗
PubMed1994

Bladder tumours in Chinese: a 6 year study.

Specimens from 334 Chinese patients who underwent surgical treatment for bladder tumours over a 6 year period were studied retrospectively. Transitional cell carcinoma (TCC) accounted for 91.3% of all the bladder tumours. The male to female ratio was 3:1 and the mean age was 69 years. Papillary TCC, which represented 67.5% of all TCC, were more often of a lower grade compared to non-papillary tumours. The staging of tumours was done for the 102 cystectomy specimens with TCC only. Among these, 28% were superficial while 72% were muscle-invasive and the papillary TCC usually presented at an earlier stage. Infiltration into the prostate gland was identified in 11% of male patients while coexisting adenocarcinoma of the prostate was observed in another 4.2%. Other types of carcinoma were uncommon. Squamous cell carcinoma, adenocarcinoma and small cell carcinoma accounted for 2.7, 1.8 and 0.6% of all bladder tumours, respectively. A rare case of sarcomatoid carcinoma was also found, but no true sarcoma was documented in this series. Benign lesions included five inverted papillomas, three nephrogenic adenomas, two paragangliomas and one haemangioma.

Adenocarcinoma↗
PubMed1994

Prevalence of human papillomavirus types 16 and 18 in penile carcinoma: a study of 41 cases using PCR.

AIMS: To determine retrospectively the prevalence of human papillomavirus (HPV) types 16 and 18 in penile carcinomas. METHODS: Forty one surgically resected penile carcinomas from the archives at Queen Mary Hospital, Hong Kong, were reviewed and classified into verrucous carcinoma, and well, moderately, and poorly differentiated squamous cell carcinomas. Paraffin wax embedded tumour tissue was sectioned and analysed for HPV 16 and HPV 18 using the polymerase chain reaction with type specific internal probes. RESULTS: There were seven verrucous carcinomas, and 11 well, 17 moderately, and six poorly differentiated squamous cell carcinomas. Six of the 41 (15%) patients had penile carcinoma containing HPV 16 or HPV 18 DNA, or both, with HPV 16 found in four (10%) and HPV 18 in four (10%). The mean ages of HPV positive and HPV negative groups of patients were 68.5 and 57.6 years, respectively (p < 0.05). None of the seven verrucous and 11 well differentiated squamous cell carcinomas was positive for HPV. The mean age of patients who had these carcinomas was 52.4 years. As a group, these low grade carcinomas occurred in patients younger by more than a decade than those who had carcinomas of the higher grades (mean age 64.4 years; p < 0.01). CONCLUSIONS: Penile carcinomas had much lower rates of infection by HPV 16 or HPV 18 than cervical carcinomas in this Hong Kong population. Based on our findings and on data collated from published findings, it is concluded that penile verrucous carcinomas are not associated with HPV 16 and HPV 18. The overall low prevalence of HPV 16 and HPV 18 in penile carcinomas suggests that other HPV types might be important in the pathogenesis of these tumours.

Aged↗