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Biomedical subjects

A C Chan

Publications and source records attributed to A C Chan.

At least 181 records · Page 10Linked to original sources

The role of protein tyrosine kinases and protein tyrosine phosphatases in T cell antigen receptor signal transduction.

Engagement of the T cell antigen receptor (TCR) by peptide antigen bound to the major histocompatibility complex (MHC) molecules initiates a biochemical cascade involving protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPases). Recent biochemical and genetic evidence has implicated at least three cytoplasmic protein tyrosine kinases (PTKs), Lck, Fyn, and ZAP-70, that are involved in the initiation of TCR signal transduction. In addition, genetic evidence has demonstrated the requirement of the transmembrane PTPase, CD45, for TCR function. Activation of T cells through the TCR represents an alteration in the dynamic equilibrium between PTKs and PTPases. The TCR is a multi-subunit complex composed of at least six different gene products. Dissection of the TCR utilizing chimeric receptors and TCR mutants has demonstrated that the multi-subunit receptor is composed of at least two signal transducing modules, the CD3 and the zeta chain subunits. These two modules have in common peptide sequences within their cytoplasmic domains termed antigen recognition activation motifs (ARAMs) that are responsible for transducing signaling events. Moreover, the ARAM sequence is also found in subunits associated with a variety of other hematopoietic cell antigen receptors and is likely to form the basis for interactions with effector molecules within the signaling cascades of these receptors. Here we review the mechanism by which the ARAM sequences interact with PTKs and the cascades of PTKs and PTPases that are involved in mediating TCR function.

Amino Acid Sequence↗

Laparoscopic cholecystectomy: results of first 300 cases in Hong Kong.

Prospective analysis of the first three hundred patients who underwent laparoscopic cholecystectomy was carried out in three surgical centres of Hong Kong. Over a 20-month period, 300 consecutive patients were recruited, including elective and emergency cases. The indications for laparoscopic cholecystectomy were symptomatic gallstones (78%), cholangitis (6%), pancreatitis (5%) and cholecystitis (11%). Patients with common duct stones (12) had preoperative endoscopic sphincterotomy and stone extraction prior to cholecystectomy. Laparoscopic cholecystectomy was accomplished successfully in 287 patients. Thirteen patients (4.3%) required conversion to open cholecystectomy. The reasons for conversion were: inability to identify cystic duct and common bile duct clearly (6); bleeding (5); Mirizzi syndrome (1); and slippage of cystic duct clip (1). The median operation time was 80 min with a range of 28-270 min. The median hospital stay was 3 days. Seventy-five per cent of patients required only a single dose of pethidine injection. None of the patients required blood transfusion. The overall complication rate was 7%. These included mild cellulitis of the subumbilical wound (3%) and postoperative chest infection (3%). One patient developed subphrenic abscess which resolved on percutaneous drainage under ultrasound guidance. Iatrogenic injury to the common bile duct was seen in one patient who had an impacted stone at Hartmann's pouch. With adequate training laparoscopic cholecystectomy can be performed safely. The advantages over open cholecystectomy are less wound pain, better cosmesis and shorter convalescence.

Cholecystectomy↗

Functional characterization of a signal transducing motif present in the T cell antigen receptor zeta chain.

A conserved sequence motif has been identified in a number of signaling subunits associated with hematopoietic cell antigen receptors. Here, we characterize signaling by a 17 amino acid motif that is triplicated in the T cell antigen receptor zeta chain. Analysis of zeta truncations and constructs containing the isolated motif demonstrates that this motif is sufficient for the induction of both proximal and distal events associated with T cell activation. Stimulation of truncations that contain either one, two, or three copies of the motif results in induction of an identical pattern of tyrosine phosphoproteins. Moreover, triplication of the NH2-terminal zeta motif results in enhanced signaling, suggesting a redundant role in signal amplification for the three motifs in zeta. Finally, we demonstrate the association of a recently identified protein tyrosine kinase ZAP-70 with this motif, and provide evidence for its involvement in zeta function.

Amino Acid Sequence↗

Fine-needle aspiration of cutaneous malakoplakia.

A 99-yr-old Chinese woman with cutaneous malakoplakia and concomitant urinary tract infection was reported. The patient presented with an ulcerated right lower quadrant mass and computerized tomography showed that it was limited to the skin and subcutaneous tissue with no extension to the pelvic or abdominal structures. The patient also suffered from urinary tract infection and was treated with oral norfloxacin. The ulcerated subcutaneous mass disappeared on follow-up visit 6 months after presentation. The cytologic (fine-needle aspiration), histologic (trucut biopsy) and ultrastructural features of cutaneous malakoplakia were described. The possible usefulness of fine-needle aspiration in the diagnosis of this condition was discussed.

Abdomen↗

A double-blind randomized controlled trial comparing sodium tetradecyl sulphate and ethanolamine oleate in the sclerotherapy of bleeding oesophageal varices.

The efficacy and side effects of 3% sodium tetradecyl sulphate (STD) and 5% ethanolamine oleate (ETH) were compared in 95 patients admitted with variceal bleeding. The patients were allocated in a randomised fashion to one of the treatment groups when varices were identified which were either actively bleeding or had signs of recent haemorrhage. Endoscopic examination was performed within 24 hours of admission. The endoscopist had no knowledge of which sclerosant was used. Intravariceal injections of 2 ml aliquots up to a maximum of 20 ml were made in a double-blinded manner. Repeat injections were performed at weekly intervals until all oesophageal varices were obliterated. Bleeding was successfully controlled in 42/48 (87.5%) patients in the STD group and 41/47 (87.2%) patients in the ETH group after one session of therapy. Variceal obliteration was achieved after 3.3 +/- 1.3 sessions of STD and 4.5 +/- 1.9 sessions of ETH (p < 0.05 Student's t-test). Post-injection pyrexia was significantly more common in the STD group (42% vs 30% p < 0.05, chi-square test). There was no difference in the rates of subsequent oesophageal ulceration, stricture formation or perforation of the oesophagus. It is concluded that STD and ETH are both effective in controlling variceal haemorrhage, but STD obliterates the varices in significantly fewer sessions.

Double-Blind Method↗

Latent sites of Epstein-Barr virus infection.

Epstein-Barr virus (EBV) has been detected in a wide spectrum of tumors. This study investigates the detection rate of EBV-DNA by Southern blot hybridization analysis (SOBH) and polymerase chain reaction (PCR) in different tissues from persons without apparent EBV-related diseases. Of 20 tonsillectomy specimens studied, SOBH indicated positivity for EBV-DNA in 1 case, and PCR indicated positivity in 10. In autopsies performed on patients with no apparent evidence of EBV-related diseases, the viral DNA was only detected by PCR in the following: parotid gland (7/15), submandibular gland (8/20), nasopharynx (8/10), tonsil (8/10), larynx (5/6), lung (5/9), cervical lymph node (7/10), mediastinal lymph node (7/10), abdominal lymph node (4/10), spleen (6/10), thyroid (5/10), liver (1/10), pancreas (1/4), kidney (4/10), uterine cervix (1/4), ovary (1/5) and testis (1/3). These results provide a baseline for interpreting the role of EBV in carcinogenesis.

Adolescent↗

Usefulness of follicular dendritic cell pattern in classification of peripheral T-cell lymphomas.

Classification of peripheral T-cell lymphomas based on morphological criteria can present problems due to overlap in histological features amongst the subtypes. An immunohistochemical study was designed to study the follicular dendritic cell patterns in 21 cases of peripheral T-cell lymphoma which had been classified using the updated Kiel classification. Three patterns of distribution were observed: 1 follicular dendritic cells not detected (3 cases); 2 follicular dendritic cells restricted to remnant follicle centres (7); 3 follicular dendritic cells present as an expanded network of cells exceeding the confines of germinal centres (11). Ten out of 11 angioimmunoblastic lymphomas showed an expanded network of follicular dendritic cells. The only negative case showed features which, on review, were in keeping with a pleomorphic, medium and large cell lymphoma showing an unusual proliferation of small venules. Other than angioimmunoblastic lymphomas, only one other case showed follicular dendritic cell hyperplasia. This was an unclassified peripheral T-cell lymphoma. We conclude that follicular dendritic cell hyperplasia may be used an an aid to diagnosis of the angioimmunoblastic type of peripheral T-cell lymphoma, and we recommend the routine staining of these cells in typing of T-cell lymphomas to facilitate comparison between centres.

Antibodies, Monoclonal↗

Paraganglioma of the urinary bladder: an immunohistochemical study and report of an unusual association with intestinal carcinoid.

Two cases of paraganglioma of the urinary bladder are reported. Their immunohistochemical profiles and the clinical features are compared with other cases in the literature. The three pan-endocrine markers (neuron-specific enolase, synaptophysin and chromogrannin) were positive in both cases. Positivity to other neuropeptides (including the present two cases and those in literature) includes adrenocorticotropic hormone (three out of five cases), calcitonin (two out of nine cases), gastrin (two out of six cases), glial fibrillary acidic protein (one out of five cases), glucagon (two out of six cases), serotonin (five out of nine cases), and somatostatin (four out of eight cases). A previously unmentioned association between paraganglioma of the urinary bladder and carcinoid in the gastrointestinal tract is noted in one of the present cases. This peculiar association highlights the importance of multiplicity of tumours of the neuroendocrine system other than the classical multiple endocrine neoplasia syndromes.

Adult↗

Periosteal Gaucher-like cells in beta-thalassemia major.

A 24-year-old Chinese woman who has undergone staged surgery for craniofacial deformity secondary to beta-thalassemia major is presented. Local clusters of Gaucher-like cells were found in the periosteum of the mandible. The histologic and ultrastructural features of these cells are described and the pathogenesis and differential diagnoses discussed. To the best of our knowledge, this is the first reported case of Gaucher-like cells occurring outside the lymphohematopoietic system in thalassemic patients.

Adult↗

Partners in defense, vitamin E and vitamin C.

In addition to the enzymic mechanism of free-radical removal, essential nutrients that can scavenge free radicals, such as vitamins E and C, constitute a strong line of defense in retarding free radical induced cellular damage. Distinct pathways for the repair of oxidized vitamin E in human cells have been recently identified. Within 0.5 min after the addition of arachidonic acid to a human platelet homogenate, over half of the platelet vitamin E and added arachidonate were metabolized by platelet cyclooxygenase and lipoxygenase pathways. After adding nordihydroguaiaretic acid, a lipoxygenase inhibitor and a strong reductant, over 60% of the oxidized vitamin E was regenerated. To test other physiological, water-soluble reductants that may help regenerate vitamin E, eicosatetraynoic acid, a lipoxygenase inhibitor that is not an antioxidant, was used. In this system, both ascorbate and glutathione provided significant vitamin E regeneration. Kinetic analysis and studies of vitamin E regeneration in a protein-denaturing system revealed that ascorbate regenerates vitamin E by a nonenzymic mechanism, whereas glutathione regenerates vitamin E enzymatically. These studies suggest that significant interaction occurs between water- and lipid-soluble molecules at the membrane-cytosol interface and that vitamin C may function in vivo to repair the membrane-bound oxidized vitamin E.

Animals↗

Intracytoplasmic barium salts in pleural fluid.

Cytological examination of the pleural effusion fluid obtained from a 66-yr-old Chinese lady showed numerous intra- and extracytoplasmic colourless refractile non-birefringent crystals. X-ray analysis of the crystals identified barium salts. On further inquiry, it was learnt that the fluid obtained had been placed in a specimen bottle provided by the x-ray department. This container was presumably contaminated with barium salts. The case highlights an unusual aspect of specimen contamination and the usefulness of x-ray analysis in the identification of crystals/substances.

Aged↗

Tumors of the heart. A 20-year experience with a review of 12,485 consecutive autopsies.

Cardiac involvement by primary and secondary tumors is one of the least investigated subjects in oncology. Seven cases of primary and 154 cases of secondary cardiac tumors from autopsies performed over a 20-year period (1972 through 1991) at Queen Mary Hospital, Hong Kong, were reviewed. During this period, 12,485 autopsies were performed, and the autopsy incidence for primary and secondary heart tumors is thus 0.056% and 1.23%, respectively. Only seven primary cardiac tumors were found, including two myxomas, two rhabdomyomas, two hemangiomas, and one lipoma. For secondary tumors involving the heart (including both metastasis and local extension), important primary tumors in male subjects were carcinoma of the lung (31.7%), esophageal carcinoma (28.7%), lymphoma (11.9%), carcinoma of the liver (6.9%), leukemia (4.0%), and gastric carcinoma (4.0%), while in female subjects, carcinoma of the lung (35.9%), lymphoma (17.0%), carcinoma of the breast (7.5%), and pancreatic carcinoma (7.5%) predominated. Overall, the three most common malignant neoplasms encountered were carcinoma of the lung, esophageal carcinoma, and lymphoma. Pericardium, including epicardium, was the most common location of cardiac involvement by secondary tumors, followed by myocardium and endocardium. The present study showed a higher percentage of esophageal carcinoma and carcinoma of the liver (reflecting the higher incidence of these tumors in Hong Kong Chinese), but a lower incidence of carcinoma of the breast when compared with other series. The metastatic lung tumors showed an unusual predominance of adenocarcinoma.

Adolescent↗

Isolated right-sided endocarditis in Hong Kong Chinese.

Thirteen histologically-proven cases of endocarditis confined to the right side of the heart were found in 9406 consecutive autopsies. Eleven cases involved the tricuspid valve and two the atrial endocardium. Nine cases were in males and 4 in females. Only one case showed underlying valvular/endocardial disease. Eight cases were infective, with Staphylococcus aureus being the predominant organism, and 5 non-infective. For the infective cases, intravenous drug abuse was the commonest predisposing factor, and malignancy the commonest association for the non-infective. The commonest overall complication was lung abscess due to septic emboli in the 3 drug addicts, a common association in other reported series. These latter cases are particularly important to recognize, being generally more responsive to treatment than left-sided infective endocarditis.

Causality↗

A review of clinicopathologic features of pheochromocytomas in Hong Kong Chinese.

Twenty-two Chinese patients with pheochromocytomas including 18 surgical and four autopsy cases were reported. The incidence at autopsy was 0.048%. The tumours were most common in the sixth and the fourth decades in males and females, respectively. There was no sex predilection. The incidence of bilaterality was 4.5% and the tumours were more common on the right side. 9.1% of the tumours were malignant and they were larger than their benign counterparts. Solid and diffuse pattern and mixed pattern were the most common histologic patterns. Minor histological features included hyaline globules (64%), nuclear pseudo-inclusions (55%), lipid degeneration (4.5%) and peri-adrenal brown fat (18%). All of them were strongly positive for the three pan-neuroendocrine markers (neuron-specific enolase, synaptophysin and chromogranin) confirming the usefulness of these markers in diagnosing pheochromocytoma.

Adolescent↗

ZAP-70: a 70 kd protein-tyrosine kinase that associates with the TCR zeta chain.

Protein-tyrosine kinases (PTKs) play an integral role in T cell activation. Stimulation of the T cell antigen receptor (TCR) results in tyrosine phosphorylation of a number of cellular substrates. One of these is the TCR zeta chain, which can mediate the transduction of extracellular stimuli into cellular effector functions. We have recently identified a 70 kd tyrosine phosphoprotein (ZAP-70) that associates with zeta and undergoes tyrosine phosphorylation following TCR stimulation. Here we report the isolation of a cDNA clone encoding ZAP-70. ZAP-70 represents a novel PTK and is expressed in T and natural killer cells. Moreover, tyrosine phosphorylation and association of ZAP-70 with zeta require the presence of src family PTKs and provide a potential mechanism by which the src family PTKs and ZAP-70 may interact to mediate TCR signal transduction.

Amino Acid Sequence↗

Regeneration of vitamin E in rat polymorphonuclear leucocytes.

The objectives of this study were to determine whether the recycling of tocopherol occurs in elicited rat polymorphonuclear leukocytes and if so, whether the recycling process is enzymic or chemical. When incubated with hemoglobin, tocopherol was oxidized in cell homogenates in a time- and concentration-dependent manner. The oxidized tocopherol could be regenerated by addition of ascorbate, glutathione or nordihydroguaiaretic acid. Time course studies showed a rapid regeneration of tocopherol which peaked at 1 min after the addition of reductants. Determination of the regeneration reaction in the presence of CHCl3 and MeOH indicated that under these enzyme-denaturing conditions, a considerable amount of tocopherol was still regenerated, suggesting that the regeneration reaction is predominantly a chemical reaction. This study provided direct evidence from mass analysis that oxidized vitamin E can be regenerated by cellular water-soluble reductants such as ascorbate and glutathione.

Animals↗