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Biomedical subjects

A C Chan

Publications and source records attributed to A C Chan.

At least 19 recordsLinked to original sources
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

Comparative uptake of alpha- and gamma-tocopherol by human endothelial cells.

The intake of gamma-tocopherol by North Americans is generally higher than that of alpha-tocopherol. However, the levels of alpha-tocopherol in human blood have consistently been shown to be higher than those of gamma-tocopherol suggesting differential cellular retention of the two tocopherol forms. We sought to resolve this question by studying tocopherol metabolism by human endothelial cells in culture. The time- and dose-dependent uptake of gamma-tocopherol by endothelial cells was similar to that of alpha-tocopherol. To determine the comparative uptake between alpha- and gamma-tocopherol, we adopted two approaches in which cells were enriched with either increasing concentrations of an equimolar mixture of alpha- and gamma-tocopherol; or cells were enriched with a fixed concentration of tocopherols in which the alpha to gamma ratio was varied. Our results indicated that there was a preferential uptake of gamma-tocopherol by the cells. When cells were enriched with either alpha- or gamma-tocopherol and the disappearance of individual tocopherols was monitored over time, gamma-tocopherol exhibited a faster rate of disappearance. The faster turnover of gamma-tocopherol can explain the discrepancy between high intake and low retention of gamma-tocopherol in man.

Cells, Cultured↗
PubMed1992

Tuberculous myocarditis presenting as sudden cardiac death.

A 71-year-old Chinese male presented as sudden death and autopsy revealed miliary tuberculosis with tuberculous myocarditis. Though miliary tuberculosis is not as common as in the past, it remains one of the possible causes of sudden cardiac death.

Aged↗
PubMed1992

New insights into T-cell antigen receptor structure and signal transduction.

Recent studies have provided insights into how the complex structure of the T-cell antigen receptor relates to its signal transduction function. Both the CD3 and zeta subunits contain functioning signaling modules that regulate the activation of tyrosine kinases and phosphorylation of cellular substrates.

Amino Acid Sequence↗
PubMed1992

Aortic aneurysm at autopsy: a five year survey in Hong Kong.

The authors reviewed 3133 consecutive autopsies performed in the 5 year period from 1986 to 1990 in Queen Mary Hospital (Hong Kong), and 96 cases of aortic aneurysms were found. The incidence was 1 in 33 autopsies. The ratio of male to female was 1.8 to 1, and the disease was most common in the eighth decade of life. The majority of death was due to rupture (70%) or related atherosclerotic diseases (14%), and the majority of aneurysms were not suspected before autopsies (62%). Most of the non-dissecting aneurysms were found in the abdominal aorta, the infra-renal portion. For dissecting aneurysms, Daily's type A was much more common. Hypertension was recognized in a high proportion of cases. Accompanying diseases like syphilis, Takayasu's disease, ischemic heart disease, cerebrovascular accident, diabetes mellitus, peripheral vascular disease, and chronic obstructive airway disease were also noted.

Adult↗
PubMed1991

Evaluation of dacryocystorhinostomy failure with computed tomography and computed tomographic dacryocystography.

Five patients with dacryocystorhinostomy failures were examined with computed tomography or computed tomographic dacryocystography. In computed tomographic dacryocystography, radiopaque dye was instilled into the lacrimal sac before computed tomography to show its shape, location, and relation to surrounding structures. Problems with the bony ostium were detected in all five patients. Recurrent nasal polyposis, a retained metallic clip, and an unresected ethmoid air cell were also identified. Computed tomography and computed tomographic dacryocystography provided important information that facilitated reoperation after dacryocystorhinostomy failure.

Adolescent↗
PubMed1991

The zeta chain is associated with a tyrosine kinase and upon T-cell antigen receptor stimulation associates with ZAP-70, a 70-kDa tyrosine phosphoprotein.

Stimulation of the T-cell antigen receptor (TCR) leads to tyrosine phosphorylation of a number of cellular proteins, including phospholipase C (PLC) gamma 1 and the TCR zeta chain. We describe here a 70-kDa tyrosine phosphoprotein (ZAP-70) that associates with zeta within 15 sec following TCR stimulation. The phosphorylation of ZAP-70 and its association with zeta is independent of the other TCR chains since stimulation of a functional CD8/zeta chimeric receptor in a TCR-negative T cell leads to coprecipitation of ZAP-70 with the chimeric protein. In a Jurkat cell expressing the TCR and the CD8/zeta chimeric protein, tyrosine phosphorylation and association of ZAP-70 occurs exclusively with the stimulated receptor complex. In addition, a tyrosine kinase that does not appear to be fyn associates with the cytoplasmic domain of zeta and phosphorylates zeta and ZAP-70 in vitro.

Amino Acids↗
PubMed1991

Regeneration of vitamin E in human platelets.

Human platelets possess active lipoxygenase and cyclooxygenase which convert arachidonic acid to (12S)-12-hydroperoxy-5,8,10,14-eicosatetraenoic acid (12-HPETE) plus (12S)-12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) and thromboxane B2 plus 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT), respectively. When platelet homogenates were incubated with arachidonate, there was a rapid consumption of platelet tocopherol. Time course analysis revealed that within 0.5 min, over half of arachidonate and tocopherol were metabolized. Mass formation of 12-HPETE and 12-HETE or thromboxane B2 and HHT exceeded that of the mass of tocopherol oxidized. Preincubation with the lipoxygenase inhibitor 5,8,11,14-eicosatetraynoic acid (ETYA) completely abolished this arachidonate-induced tocopherol oxidation whereas cyclooxygenase inhibitors (indomethacin and aspirin) further potentiated tocopherol oxidation, indicating that this oxidation is closely linked with platelet 12-lipoxygenase activity. Incubation with lipoxygenase metabolites of arachidonic acid showed that only 12-HPETE caused a rapid tocopherol oxidation which was followed by a gradual tocopherol regeneration. By using nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor which is also a strong reductant, over 60% of the arachidonate-induced oxidized tocopherol was regenerated. Tocopherol regeneration declined with increasing oxidation time induced by arachidonate, and after 30-60 min virtually no regeneration could be observed, suggesting that the precursor molecule was unstable. We postulate that the precursor molecule is the tocopheroxyl radical. In the presence of ETYA, a lipoxygenase inhibitor without antioxidant properties, either ascorbate or GSH provided significant tocopherol regeneration. Kinetic studies showed that tocopherol regeneration after the addition of ascorbate was essentially completed by 1 min. By contrast, GSH addition caused a steady increase in tocopherol which peaked after 10 min of its addition. To determine whether this rapid regeneration is chemical or enzymic, regeneration was studied in the presence of chloroform and methanol. Comparison of various reductants in this denaturing condition for enzymes showed that ascorbate and NDGA afforded significant regeneration whereas GSH was ineffective, indicating that there are distinct enzymic and non-enzymic mechanisms for tocopherol regeneration. This study provides direct evidence from mass analysis that tocopherol can be regenerated in human cell homogenates. This finding implies that maintenance of membrane tocopherol status may be an essential function of ascorbate and GSH which operate in concert to ensure maximum membrane protection against oxidative damage.

Arachidonate 12-Lipoxygenase↗
PubMed1991

T-lymphoblastic lymphoma arising in the small intestine.

The authors report the clinical, pathological and immunological features of a case of T-lymphoblastic lymphoma presenting with protein-losing enteropathy. There was extensive multifocal involvement of the duodenum, jejunum and ileum. The mediastinum was not enlarged; the peripheral blood picture and bilateral bone marrow trephine biopsies were unremarkable. The tumor cells were positive for terminal deoxynucleotide transferase, CD3, CD2, CD7 and CD10; they were negative for CD1, CD5, CD4, CD8 and HLA-DR. The immunophenotype was that of an immature thymic T-cell. Monocytic and B-cell markers were negative. Despite initial dose reduction in chemotherapy, the patient still developed massive intestinal hemorrhage and succumbed 2 wks after treatment. Postmortem examination confirmed absence of thymic involvement. The overall picture strongly suggests a primary intestinal origin of this T-lymphoblastic lymphoma which contradicts the conventional wisdom that T-lymphoblastic lymphoma arises in the thymus from primitive cortical lymphocytes before rapidly disseminating.

Adult↗
PubMed1991

Lacrimal obstruction after medial maxillectomy.

Medial maxillectomy can result in lacrimal obstruction and the need for subsequent dacryocystorhinostomy. Computed tomographic dacryocystography is a technique in which radiopaque dye is instilled in the lacrimal sac and computed tomography is subsequently performed. Computed tomographic dacryocystography facilitated the management of a patient with lacrimal obstruction after medial maxillectomy by helping to exclude recurrent tumor and sinusitis, and by providing a surgical "roadmap" in the presence of altered anatomy.

Adult↗
PubMed1991

Nonbacterial thrombotic endocarditis in Hong Kong Chinese.

Fifty-two Hong Kong Chinese cases of nonbacterial thrombotic endocarditis at autopsy were reviewed to ascertain if there was any difference in autopsy incidence, associated diseases, age and sex incidence, distribution of infarcts, and pattern of valve involvement compared with that in previously reported series. The overall autopsy incidence was 0.68%, within the range of previous reports. Forty-one cases (79%) were associated with malignant neoplasms; the remaining 11 cases were associated with miscellaneous disorders. Adenocarcinoma was associated with 27 (52%) of the cases. Unusual findings were the association of five cases with intrahepatic cholangiocarcinoma and four cases with esophageal squamous carcinoma. This is explicable on the basis of a higher incidence of these two tumors in Hong Kong Chinese than in Western populations, ie, the source of most other reported series. Sex and age incidence, the distribution of infarcts, and the pattern of valve involvement were similar to those reported in other series of nonbacterial thrombotic endocarditis.

Adolescent↗
PubMed1991

Danazol therapy in autoimmune hemolytic anemia associated with systemic lupus erythematosus.

We describe a patient with systemic lupus erythematosus (SLE) complicated by severe autoimmune hemolytic anemia. Therapy with corticosteroids, splenectomy, azathioprine, chlorambucil, and intravenous immunoglobulin was unsuccessful. She responded to danazol, however, with maintenance of her hemoglobin and reductions in her transfusion and corticosteroid requirement. Thus, danazol may represent an important therapeutic option in the treatment of autoimmune hemolytic anemia.

Adrenal Cortex Hormones↗
PubMed1990

R,R,R-alpha-tocopherol potentiates prostacyclin release in human endothelial cells. Evidence for structural specificity of the tocopherol molecule.

Human umbilical vein endothelial cells (HUVEC) in culture synthesize prostacyclin (PGI2) as the predominant metabolite of arachidonic acid which is derived from the deacylation of phospholipids. Under basal-unstimulated condition, PGI2 release from HUVEC is extremely low; however, when endothelial monolayers were preincubated with the natural vitamin E (R,R,R-alpha-tocopherol), we found a dose-dependent potentiation of basal PGI2 release. When HUVEC were stimulated with arachidonate or ionophore A23187, there was a dose-dependent increase of PGI2 release in response to tocopherol enrichment. When HUVEC were labelled with [Me-3H]choline followed by A23187 stimulation, a significantly higher lysophosphatidylcholine was found in the tocopherol-enriched cells, suggesting a change in enzymes involved in phosphatidylcholine metabolism. Analysis of these enzymes revealed that phospholipase A2 activity was enhanced by tocopherol enrichment, whereas lysophospholipase and acyl-CoA acyltransferase were unaffected. To determine the specificity of the tocopherol molecule, different analogues were tested for their PGI2 potentiating activity. Results showed that the free hydroxyl group on the chromanol ring as well as the phytyl side-chain are absolutely required to stimulate PGI2 release, whereas, different methyl locations and substituents on the chromanol ring had no effect. These studies demonstrated that tocopherol potentiates basal PGI2 release in HUVEC and in contrast to its reported inhibitory role in rat platelets, myocardium and neutrophils, tocopherol stimulates phospholipase activity in HUVEC.

Acetyl-CoA C-Acyltransferase↗
PubMed1990

Low anterior resection of the rectum using a double stapling technique.

Using a double stapling technique in 30 patients, anterior resection of the rectum was attempted for low rectal carcinoma (n = 28), giant rectal adenoma (n = 1) and radiation-induced rectal stricture (n = 1). There were three emergency operations. The rectum was stapled transversely more than 3 cm below the tumour using the adjustable-angle linear stapler (Roticulator). Colorectal or coloanal anastomoses were constructed using the EEA circular stapler introduced per anum through the anorectal stump staple line. Ten coloanal and 19 low rectal anastomoses were achieved. A protecting transverse loop colostomy was fashioned in one patient with coloanal anastomosis who developed a vaginal tear during the procedure. In one patient technical failure necessitated conversion to abdominoperineal excision of the rectum. All staple rings and resection margins were intact and free from tumour. There were two clinical anastomotic leaks, both treated successfully with a defunctioning transverse loop colostomy. One patient developed a small infective pelvic haematoma 2 weeks after surgery which required drainage. Hospital stay ranged from 6 to 15 days (mean 8 days). Continence was normal in all patients at 8 weeks. One soft coloanal anastomotic stricture required dilatation. No recurrences have been detected during a follow-up of between 10 and 22 months.

Adult↗