Biomedical subjects

F K Chan

Publications and source records attributed to F K Chan.

89 records · Page 5Linked to original sources

PubMed1995

A role for the orphan steroid receptor Nur77 in apoptosis accompanying antigen-induced negative selection.

The transcription factor Nur77, an orphan member of the nuclear hormone receptor superfamily, is highly expressed during T cell receptor-signaled apoptosis, suggesting a possible role for Nur77 in negative selection. We examined this by generating two sets of transgenic mice. In one set of mice, a dominant-negative Nur77 mutant is constitutively expressed and the other in which wild-type Nur77 protein is constitutively expressed in developing thymocytes. We report that inhibition of endogenous Nur77 by the dominant-negative mutant perturbed T cell development and inhibited antigen-induced negative selection in F5T cell receptor transgenic mice. Constitutive expression of wild-type Nur77 protein induced apoptosis in developing thymocytes, resulting in a decreased number of thymocytes and mature T cells. Together, these data support a role for Nur77 in the downstream signaling events in antigen-induced negative selection.

Animals↗

PubMed1995

Identification of human and mouse p19, a novel CDK4 and CDK6 inhibitor with homology to p16ink4.

The cell cycle in mammalian cells is regulated by a series of cyclins and cyclin-dependent kinases (CDKs). The G1/S checkpoint is mainly dictated by the kinase activities of the cyclin D-CDK4 and/or cyclin D-CDK6 complex and the cyclin E-CDK2 complex. These G1 kinases can in turn be regulated by cell cycle inhibitors, which may cause the cells to arrest at the G1 phase. In T-cell hybridomas, addition of anti-T-cell receptor antibody results not only in G1 arrest but also in apoptosis. In searching for a protein(s) which might interact with Nur77, an orphan steroid receptor required for activation-induced apoptosis of T-cell hybridomas, we have cloned a novel human and mouse CDK inhibitor, p19. The deduced p19 amino acid sequence consists of four ankyrin repeats with 48% identity to p16. The human p19 gene is located on chromosome 19p13, distinct from the positions of p18, p16, and p15. Its mRNA is expressed in all cell types examined. The p19 fusion protein can associate in vitro with CDK4 but not with CDK2, CDC2, or cyclin A, B, E, or D1 to D3. Addition of p19 protein can lead to inhibition of the in vitro kinase activity of cyclin D-CDK4 but not that of cyclin E-CDK2. In T-cell hybridoma DO11.10, p19 was found in association with CDK4 and CDK6 in vivo, although its association with Nur77 is not clear at this point. Thus, p19 is a novel CDK inhibitor which may play a role in the cell cycle regulation of T cells.

Amino Acid Sequence↗

PubMed1995

Endoscopic sphincterotomy-induced hemorrhage: a study of risk factors and the role of epinephrine injection.

BACKGROUND: We studied the incidence and relative risk factors for postsphincterotomy bleeding and the efficacy of epinephrine injection in hemostasis. METHODS: We retrospectively analyzed the incidence of postsphincterotomy bleeding in 983 consecutive patients with sphincterotomy for common duct stones and risk factors for such bleeding, i.e., presence of coagulopathy, stone impaction, periampullary diverticulum, extension of previous sphincterotomy, and use of needle knife precut sphincterotomy in sphincterotomy-induced bleeding. Epinephrine irrigation was performed for mild bleeding, and injection with 1:10,000 epinephrine was performed to control more severe bleeding. RESULTS: 119 patients (12.1%) developed postsphincterotomy bleeding; 114 patients had immediate bleeding and 5 had delayed hemorrhage. Stone impaction at the papilla, periampullary diverticulum, and extension of a previous sphincterotomy were independent variables that increased the risk of bleeding. Forty-six percent of 119 patients with mild bleeding responded to epinephrine irrigation. The remaining required injection therapy with 1:10,000 epinephrine. Initial hemostasis was achieved in all. Rebleeding occurred in 5 patients but all responded to conservative management. None required emergency surgery and there was no mortality related to uncontrolled hemorrhage. CONCLUSION: Epinephrine injection is a safe treatment for sphincterotomy-induced bleeding.

Adult↗

PubMed1994

Anti-neutrophil cytoplasmic antibodies (ANCA) and inflammatory bowel diseases in Chinese.

Inflammatory bowel diseases are uncommon in the Chinese, but the incidence is rising. Their differentiation from infective colitis is often not clear-cut and diagnosing inflammatory bowel diseases can be difficult in Asia. We have studied Chinese patients with ulcerative colitis (N = 19) and Crohn's disease (N = 12) for anti-neutrophil cytoplasmic antibodies (ANCA) by indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assays (ELISA). Patients with enteric fever (N = 29) and irritable bowel syndrome (N = 24) were recruited as controls. Seventy-three percent of ulcerative colitis patients exhibited either p-ANCA (31%) or c-ANCA (42%) by IIF. Twenty-five percent of Crohn's disease patients were found to be p-ANCA positive. However, these ANCA were nonreactive to anti-alpha granule, antiproteinase 3, antimyeloperoxidase, or antilactoferrin. All positive patients had extensive colitis. Sera collected from patients suffering from enteric fever and irritable bowel syndrome were negative for ANCA by IIF and ELISA. We concluded that the detection of ANCA is helpful in diagnosing inflammatory bowel diseases. Further attempts to characterize these autoantibodies are needed.

Adult↗

PubMed1994

Crohn's disease in the Chinese population. An experience from Hong Kong.

PURPOSE: Crohn's disease was extremely rare among Chinese. We reviewed all cases diagnosed as having Crohn's disease during a five-year period. METHODS: A diagnosis of Crohn's disease was made only if all of the following criteria were fulfilled: 1) clinical symptom(s) and sign(s) compatible with chronic inflammatory bowel disease; 2) exclusion of intestinal infection by repeated stool cultures; 3) macroscopic features of small and/or large intestinal inflammation with skip lesion, stricture, and fistula formation; 4) histologic features of Crohn's disease, i.e., focal lymphoid aggregate, focal cryptitis, and granuloma formation; 5) clinical response to conventional therapy for inflammatory bowel disease. RESULTS: Fifteen ethnic Chinese patients were diagnosed as having Crohn's disease in this period. All patients had colitis, whereas small intestine inflammation was documented in only 47 percent of patients. Extraintestinal manifestations were uncommon except for arthropathy: ankylosing spondylitis (2), sacroiliitis (1), juvenile rheumatoid arthritis (1), and colitic arthritis (1). The majority of our patients responded to medical therapy. Surgery was undertaken in 33 percent of patients. CONCLUSION: Although there is a general increased incidence of Crohn's disease in the Western world, we too are beginning to see more cases in the Far East. Nevertheless, gastrointestinal infection with bacteria and/or parasites should still be carefully excluded in these countries.

Adolescent↗

PubMed1994

A role for the cytoplasmic tail of the beta chain of CD8 in thymic selection.

The CD8 coreceptor plays a critical role in the recognition of foreign antigens by mature T cells and in the development of class I-restricted T cells. CD8 can be expressed on the surface of T cells as either a heterodimer composed of an alpha and beta chain, or as a homodimer composed of two alpha chains. In this report, we show that a CD8 beta transgene that lacks a cytoplasmic domain can suppress expression of wild-type endogenous CD8 beta and act as a dominant negative mutation. We show that this dominant negative CD8 beta transgene interferes with the development of mature CD8 T cells to different extents depending on the individual class I-restricted TCR. These data suggest CD8 beta plays a role in thymic development, and that different class I-restricted TCRs differ in their dependence on the cytoplasmic tail of CD8 beta.

Animals↗

PubMed1993

Octreotide infusion or emergency sclerotherapy for variceal haemorrhage.

To compare octreotide with injection sclerotherapy in the treatment of acute variceal haemorrhage, patients admitted with gastrointestinal bleeding and oesophageal varices confirmed by endoscopy were randomised to receive either emergency sclerotherapy with 3% sodium tetradecyl sulphate or octreotide (50 micrograms intravenous bolus plus 50 micrograms per h intravenous infusion for 48 h). At the end of the study period (48 h), the octreotide group also had sclerotherapy to obliterate the varices. 100 patients were recruited. Demographic features including the aetiology of portal hypertension and the Child-Pugh's grading of the two groups were similar. Bleeding was initially controlled in 90% of patients by emergency sclerotherapy and in 84% by octreotide infusion (95% confidence interval 0-19.5, p = 0.55). There were no significant differences between the two groups in early (within 48 h of randomisation) rebleeding (16% vs 14%), blood transfusion (3 units vs 3.5), hospital stay (5 days vs 6 days), or hospital mortality (27% vs 20%). No notable side-effects were associated with octreotide. We conclude that octreotide infusion and emergency sclerotherapy are equally effective in controlling variceal haemorrhage.

Adolescent↗

PubMed1980