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Biomedical subjects

A C Chan

Publications and source records attributed to A C Chan.

At least 145 records · Page 8Linked to original sources

Granulocytic sarcoma of megakaryoblastic differentiation complicating chronic idiopathic myelofibrosis.

We report the development of soft tissue granulocytic sarcoma with megakaryoblastic differentiation in a patient with chronic idiopathic myelofibrosis, which has hitherto been undescribed. Although an artifactual signet ring appearance of the blasts was found in the formalin-fixed tissue and caused diagnostic problems, the histological appearance on B-5 fixed material and immunophenotyping confirmed the diagnosis. Cytogenetic analysis showed 47,XY,+der(1)del(1)(?p13) at initial presentation and 47,XY,del(1)(?13),+der(1)del(1)(?p13) at the time of soft tissue blastic transformation, indicating that partial trisomy 1 might be of pathogenetic significance.

Adipose Tissue↗

Regulation of antigen receptor signal transduction by protein tyrosine kinases.

The past two years have seen further clarification of the early events occurring in antigen receptor signal transduction that are mediated by the immunoreceptor tyrosine-based activation motif (ITAM). The ITAM was shown to be a specific binding site for the ZAP-70/Syk protein tyrosine kinases and the structure of this complex was solved. In addition, possible mechanisms of activation and functions for these kinases were reported. Lastly, genetic studies established the critical importance of these kinases in antigen-receptor signaling and lymphocyte development.

Animals↗

Lymphoepithelioma-like carcinoma of the skin.

The histopathological findings of two cases of primary lymphoepithelioma-like carcinoma (LELC) of the skin occurring in two elderly Chinese individuals are presented. Microscopically, they were well circumscribed and were composed of irregular nests of malignant epithelial cells in a background of reactive lymphoid cells including mature plasma cells. A focus of epithelial dysplasia was noted in the adjacent epidermis in one case, suggesting that the LELC might have originated from the overlying epidermis. The epithelial nature of the tumors was confirmed by cytokeratin staining. In situ hybridization for Epstein-Barr virus-encoded RNA (EBER) showed that the tumor cells were uniformly negative, although positive signals were detected in scattered background lymphocytes in case 1. Our results confirm the previous observation that LELC of skin is not related to Epstein-Barr virus, even in Chinese subjects. Nevertheless, such negative findings may prove to be of diagnostic value in excluding the alternative more common diagnosis of metastatic nasopharyngeal carcinoma, which is uniformly positive for EBER.

Aged↗

Follicular dendritic cell tumor of the liver. Evidence for an Epstein-Barr virus-related clonal proliferation of follicular dendritic cells.

Tumors of the follicular dendritic cell are uncommon, and most occur as primary lymph node tumors. We report a case of primary follicular dendritic cell tumor of the liver that was initially reported as an inflammatory pseudotumor. The neoplasm recurred as two separate tumor masses 30 months after complete resection of the "hepatic inflammatory pseudotumor." It showed a wide spectrum of morphologic features ranging from areas with fascicles of very bland spindle cells amidst a background population of lymphocytes, reminiscent of inflammatory pseudotumor, to areas of dispersed sheets of highly pleomorphic tumor cells with a relative paucity of reactive inflammatory cells. The diagnosis was confirmed by positive immunohistochemical staining with CD21, CD35, R4/23, and Ki-M4 and by ultrastructural demonstration of convoluted interdigitating cell processes joined by desmosomes. The background lymphocytes were oligoclonal, CD8-positive T cells. In situ hybridization for Epstein-Barr virus (EBV)-encoded RNA was positive in the tumor cells in the original and recurrent tumors. More importantly, the cells showed identical episomal clonal EBV on Southern blot analysis, implying that the initial and recurrent tumors are due to clonal proliferation of EBV-positive neoplastic follicular dendritic cells. The tumor cells expressed latent membrane protein but not EBV-encoded nuclear antigen 2 (EBNA2) or ZEBRA. Such gene expression is very similar to that of Hodgkin's disease and nasopharyngeal carcinoma. The strong expression of latent membrane protein restricted to the tumor cells and the clonality of the EBV suggest that the virus may be involved in the pathogenesis of this tumor and not present merely as a "bystander."

Adult↗

Mesh hernioplasty using a stapler.

BACKGROUND: The recent development of laparoscopic hernioplasty has evoked extensive re-examination of the safety and effectiveness of using synthetic mesh materials in hernia surgery. We have investigated the efficacy of anterior stapling mesh repair in the treatment of inguinal hernia. METHODS: From July 1993 to June 1994, a modified open mesh hernioplasty using staples for anchorage has been performed in 127 patients. RESULTS: The mean age of patients was 61.4 +/- 13.0 years. Over 90% of them were operated on under local anaesthesia. The operation time ranged from 30 to 95 min with a median of 39 min. Only sixteen patients (12.6%) required postoperative parenteral analgesics and the median time for resuming daily activities was 7 days. Apart from two patients with reactionary haemorrhage, there was no other significant complication observed. Only one recurrence was encountered over the 26-month median follow-up period. CONCLUSIONS: We conclude that the modified mesh hernia repair with a stapling device is a feasible, inexpensive and safe procedure that is well tolerated under local anaesthesia by most patients.

Adult↗

Distinct tyrosine phosphorylation sites in ZAP-70 mediate activation and negative regulation of antigen receptor function.

Biochemical and genetic evidence has implicated two families of protein tyrosine kinases (PTKs), the Src- and Syk-PTKs, in T- and B-cell antigen receptor signaling. ZAP-70 is a member of the Syk-PTKs that associates with the T-cell antigen receptor and undergoes tyrosine phosphorylation following receptor activation. Three tyrosine residues, Tyr-292, -492, and -493, have been identified as sites of phosphorylation following T-cell antigen receptor engagement. Utilizing ZAP-70- and Syk-deficient lymphocytes (Syk-DT40 cells), we provide biochemical and functional evidence that heterologous trans-phosphorylation of Tyr-493 by a Src-PTK is required for antigen receptor-mediated activation of both the calcium and ras pathways. In contrast, cells expressing mutations at Tyr-292 or -492 demonstrate hyperactive T- and B-cell antigen receptor phenotypes. Thus, phosphorylation of ZAP-70 mediates both activation and inactivation of antigen receptor signaling.

Amino Acid Sequence↗

Collision tumour of the oesophagus: a challenge for histological diagnosis.

An unusual case of mantle cell lymphoma metastasising to squamous cell carcinoma of the oesophagus, in a 62 year old Chinese man, is reported. A histological diagnosis based on examination of a small endoscopic biopsy specimen, in the absence of detailed clinical information, may be difficult, as the lymphoma component can be mistaken for reactive lymphoid infiltrate which is sometimes present adjacent to squamous cell carcinoma. Correlation with the clinical history, careful assessment of the subtle histological changes, and use of ancillary methods such as immunohistochemistry are most helpful in making the correct diagnosis. This case also illustrates further the possible occurrence of lymphomatous infiltrates surrounding other lesions in patients with a previous or concurrent history of lymphoma.

Carcinoma, Squamous Cell↗

Choledocholithiasis: comparison of MR cholangiography and endoscopic retrograde cholangiography.

PURPOSE: To prospectively compare magnetic resonance (MR) cholangiography with endoscopic retrograde cholangiography (ERC) in the diagnosis of choledocholithiasis. MATERIALS AND METHODS: Forty-seven patients with suspected choledocholithiasis underwent non-breath-hold, heavily T2-weighted, respiratory-triggered turbo spin-echo MR cholangiography. They then underwent ERC within 5 hours. The results of the two procedures were compared in 45 patients. RESULTS: The absence of ductal dilatation was shown in 16 patients at MR cholangiography and at ERC. MR cholangiography showed common duct dilatation in 28 of the 29 patients with dilatation shown at ERC. MR cholangiography helped correctly identify 18 of the 19 patients with choledocholithiasis and 22 of the 26 patients without choledocholithiasis. Sensitivity with MR cholangiography was 95%, specificity was 85%, positive predictive value was 82%, and negative predictive value was 96%. Two of the false-positive findings were due to pneumobilia. CONCLUSION: Non-breath-hold MR cholangiography is as accurate for the evaluation of choledocholithiasis as ERC.

Adult↗

Clinical validation of the Geriatric Depression Scale (GDS): Chinese version.

This study has attempted to validate the Geriatric Depression Scale translated version (Chinese) with a psychiatric outpatient sample (N = 461) of males and females aged 60 or above, from 10 government-maintained psychiatric outpatient clinics between January 1992 and February 1993. Reliabilities and validities were exceptional. Internal consistency reliability was .89 (alpha), and the test-retest reliability was .85 (alpha). Criterion-related (psychiatrist diagnosis) validity was good at .95, and concurrent validity (with CES-D) was .96. Item analysis also confirmed consistency--all 30 items were significantly correlated with the full GDS. However, its sensitivity (70.6%), specificity (70.1%), false negatives (29.4%), and false positives (29.9%), though acceptable, were not as impressive. The overall result has shown that the GDS is generally applicable to the Chinese elderly population and is good for measuring depressive symptoms. The scale can be easily applied in the community by health care professionals. However, further follow-up studies are recommended.

Aged↗

Absence of Epstein-Barr virus in penile carcinoma. A study of 42 cases using in situ hybridization.

BACKGROUND: The relationship between Epstein-Barr virus (EBV) and carcinomas of the lower female genital tract has been the focus of some studies in recent years. However, the association between EBV and penile carcinoma never has been investigated. The aim of this study was to identify the possible role of EBV in penile carcinoma of Chinese patients. METHODS: Formalin fixed, paraffin embedded tissue of 42 cases of penile carcinoma (including 7 verrucous, 14 well differentiated, 15 moderately differentiated, and 6 poorly differentiated squamous cell carcinomas), 6 penile warts, and 9 normal penile samples were analyzed for EBV using in situ hybridization for EBV-encoded RNA (EBER). RESULTS: Epstein-Barr virus was only found in a few lymphocytes adjacent to the tumor epithelium in 12% (5 cases) of penile carcinoma. Conversely, the tumor cells, penile warts, and normal penile tissue were negative for EBV. CONCLUSIONS: The results suggest that EBV does not play a major role in the etiology of penile carcinoma.

Adult↗

Essential role for ZAP-70 in both positive and negative selection of thymocytes.

During thymic development, T cells that can recognize foreign antigen in association with self major histocompatibility complex (MHC) are selected for survival (positive selection) and autoreactive T cells are eliminated (negative selection). Both of these selective events are mediated by interaction between the T-cell receptor (TCR) and the peptide-MHC complex. But the signalling pathways that lead to cell survival or to cell death are still unclear. ZAP-70 is a protein tyrosine kinase (PTK) that is associated with the TCR signalling subunits (CD3 and zeta) and is expressed in T cells and natural killer cells. It has been shown that ZAP-70 plays a crucial role in T-cell activation and development. Here we show that mice lacking ZAP-70 had neither CD4 nor CD8 single-positive T cells, but human ZAP-70 reconstituted both CD4 and CD8 single-positive populations. Moreover, ZAP-70-/- thymocytes were not deleted by peptide antigens. Natural killer cell function was intact in the absence of ZAP-70. These data suggest that ZAP-70 is a central signalling molecule during thymic selection for CD4 and CD8 lineage.

Animals↗

Activation of ZAP-70 kinase activity by phosphorylation of tyrosine 493 is required for lymphocyte antigen receptor function.

ZAP-70 is a protein tyrosine kinase (PTK) required for T-cell development and T-cell antigen receptor (TCR) function. ZAP-70 is associated with the phosphorylated antigen receptor and undergoes tyrosine phosphorylation following receptor activation. We demonstrate here that tyrosine phosphorylation of ZAP-70 results in an increase in its catalytic activity and that this activation is mediated by the phosphorylation of tyrosine residue 493 by the src family of PTKs. The activity of baculoviral expressed ZAP-70 was up-regulated 10-fold when ZAP-70 was co-infected and phosphorylated by the src family PTK, lck. Mutation of Y493 alone abrogated the ability of ZAP-70 to be activated by lck. Moreover, we demonstrate that phosphorylation of Y493 and activation of ZAP-70 is required for antigen receptor-mediated induction of interleukin-2 (IL-2) secretion in lymphocytes.

Amino Acid Sequence↗

Analysis of the interaction of ZAP-70 and syk protein-tyrosine kinases with the T-cell antigen receptor by plasmon resonance.

Tyrosine phosphorylation of a 17-amino acid immunoreceptor tyrosine-based activation motif (ITAM), conserved in each of the signaling subunits of the T-cell antigen receptor (TCR), mediates the recruitment of ZAP-70 and syk protein-tyrosine kinases (PTKs) to the activated receptor. The interaction between the two tandemly arranged Src-homology 2 (SH2) domains of this family of PTKs and each of the phosphotyrosine-containing ITAMs was examined by real-time measurements of kinetic parameters. The association rate and equilibrium binding constants for the ZAP-70 and syk SH2 domains were determined for the CD3 epsilon ITAM. Both PTKs bound with ka and Kd values of 5 x 10(6) M-1.sec-1 and approximately 25 nM, respectively. Bindings to the other TCR ITAMs (zeta 1, zeta 2, gamma, and delta ITAMs) were comparable, although the zeta 3 ITAM bound approximately 2.5-fold less well. Studies of the affinity of a single functional SH2 domain of ZAP-70 provided evidence for the cooperative nature of binding of the dual SH2 domains. Mutation of either single SH2 domain decreased the Kd by > 100-fold. Finally, the critical features of the ITAM for syk binding were found to be similar to those required for ZAP-70 binding. These data provide insight into the mechanism by which the multisubunit TCR interacts with downstream effector molecules.

Amino Acid Sequence↗