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Biomedical subjects

A C Chan

Publications and source records attributed to A C Chan.

At least 127 records · Page 7Linked to original sources

Bcl-6 gene hypermutations in diffuse large B-cell lymphoma of primary gastric origin.

The presence of the bcl-6 gene hypermutation was studied in 40 Hong Kong Chinese patients with diffuse large B-cell lymphoma. The primary sites of involvement were nodal in 18 cases and gastric in 22. Hypermutations at the E1.11 segment of bcl-6 gene were detectable in 16/22 (73%) primary gastric and 4/18 (22%) primary nodal lymphoma (P<0.01). Three of the 22 cases of primary gastric but none of the nodal lymphoma had mutations at E1.12. The proportion of hypermutated cases in the group with bcl-6 gene rearrangement was similar to that of the germ-line group (70% v 75%). High frequency of bcl-6 gene hypermutations was found in diffuse large B-cell lymphoma of the stomach and they were independent of rearrangement of the gene as detected by Southern analysis. Unlike gene rearrangement, hypermutations of the bcl-6 gene did not appear to carry any prognostic significance clinically.

Adult↗

Two cases of fatal strongyloidiasis in Hong Kong.

Two cases of fatal strongyloidiasis associated with diabetes mellitus and malnutrition are reported. The patients presented with repeated vomiting and upper gastrointestinal bleeding respectively. Unusual findings in these two patients included: unexplained peripheral leukocytosis, pulmonary infiltrates, gastric aspirate leukocytosis, progression of gastrointestinal symptoms and concurrent presence of adult worms, eggs, filariform and rhabditiform larvae of Strongyloides stercoralis in alimentary canal specimens. Both patients succumbed while receiving treatment with mebendazole. The present report illustrates that unexplained gastrointestinal symptoms with extensive scratch marks below the umbilicus can be important clues to early diagnosis of the disease. In addition, the various presentations of S. stercoralis infestation are discussed with reference to predisposing factors. Current trends in laboratory diagnosis and therapeutic considerations are also delineated.

Aged↗

Endoscopic surgery of the oesophagus.

Conventional surgical access to the oesophagus often requires a thoracotomy. The application of techniques borrowed from laparoscopic surgery allows transthoracic dissection of oesophagus without thoracotomy. These techniques are useful in treatment of oesophageal leiomyomas, motility disorders and iatrogenic perforations. Oesophageal resection for cancer can be accomplished using minimal access, either thoracoscopically or with the aid of an operating mediastinoscope. Whether these techniques should replace transthoracic or transhiatal oesophagectomy for most patients with cancer remains to be seen.

Endoscopy↗

Giant adrenal lipoma: a report of two cases and review of literature.

Lipoma of the adrenal gland is extremely rare. We report two cases of adrenal lipomas, one in a 64-year-old female and the other a 78-year-old male. The sizes of these tumours (4.5 cm and 8 cm) were larger than those reported in the literature. Both cases were found incidentally, one at autopsy and the other during ultrasonographic examination for unrelated condition. The histogenesis, clinicopathological features, differential diagnosis and management of these cases are discussed.

Adenocarcinoma↗

Pathogenesis of gastric lymphoma: the enigma in Hong Kong.

BACKGROUND: Helicobacter pylori (H. pylori) infection has been postulated to be a pathogenetic factor in gastric lymphoma. However, the etiological factors for gastric lymphoma could vary in different populations. MATERIALS AND METHODS: We looked for histological evidence of H. pylori infection in 53 gastrectomy specimens from Hong Kong Chinese patients with primary gastric B-lymphoma. We also screened for Epstein-Barr virus (EBV) in these cases using in situ hybridization with oligonucleotide probes for EBV-encoded small RNA1 and 2. RESULTS: H. pylori was found in 29 of 53 (55%), including 8 of 13 (62%) cases of low-grade lymphoma of mucosa-associated lymphoid tissue (MALT) type. These infection rates in gastric lymphoma are lower than those reported in Western populations (80%-100%) and comparable to that found in healthy Chinese blood donors (55%) or in non-ulcer dyspeptic patients (52%-57%). EBV was found in tumor cells only in one case of high-grade gastric lymphoma with low-grade MALT component which was H. pylori-negative, and in occasional nontumor-lymphoid cells in 7 other cases. CONCLUSIONS: These results suggest that (1) the role of H. pylori in pathogenesis of gastric lymphoma may vary in different populations; (2) very few gastric lymphomas are associated with EBV; (3) not all low-grade gastric MALT lymphomas are H. pylori-dependent.

Adult↗

Vitamin E potentiates arachidonate release and phospholipase A2 activity in rat heart myoblastic cells.

Cytosolic phospholipase A2 (cPLA2) selectively catalyses the release of arachidonic acid from the sn-2 position of glycero-phospholipids to produce prostaglandins and leukotrienes. In this study, vitamin E enrichment of rat heart myoblastic H9c2 cells caused an increase in the release of arachidonate during ionophore (A23187) stimulation. PLA2 activity in the cytosolic fraction was also enhanced but enzyme activity in the particulate fraction was not affected by this treatment. Immunoblotting analysis with a polyclonal anti-cPLA2 antibody showed an increased level of the enzyme in vitamin E-treated cells. Direct incorporation of vitamin E into lipid vesicles in the assay mixture resulted in modulation of enzyme activity in a biphasic manner. Pretreatment of cells with phorbol 12-myristate 13-acetate, a known activator of protein kinase C, synergistically potentiated the ionophore-induced arachidonate release in both the control and vitamin E-treated cells. However, vitamin E treatment by itself did not affect the protein kinase C activity, indicating that the vitamin E-induced activation of cPLA2 was independent of the protein kinase C cascade. Collectively, these results suggest that vitamin E potentiates arachidonate release through the direct and/or indirect modulation of cPLA2 activity.

Animals↗

Phosphorylation of SLP-76 by the ZAP-70 protein-tyrosine kinase is required for T-cell receptor function.

Two families of tyrosine kinases, the Src and Syk families, are required for T-cell receptor activation. While the Src kinases are responsible for phosphorylation of receptor-encoded signaling motifs and for up-regulation of ZAP-70 activity, the downstream substrates of ZAP-70 are unknown. Evidence is presented herein that the Src homology 2 (SH2) domain-containing leukocyte protein of 76 kDa (SLP-76) is a substrate of ZAP-70. Phosphorylation of SLP-76 is diminished in T cells that express a catalytically inactive ZAP-70. Moreover, SLP-76 is preferentially phosphorylated by ZAP-70 in vitro and in heterologous cellular systems. In T cells, overexpression of wild-type SLP-76 results in a hyperactive receptor, while expression of a SLP-76 molecule that is unable to be tyrosine-phosphorylated attenuates receptor function. In addition, the SH2 domain of SLP-76 is required for T-cell receptor function, although its role is independent of the ability of SLP-76 to undergo tyrosine phosphorylation. As SLP-76 interacts with both Grb2 and phospholipase C-gamma1, these data indicate that phosphorylation of SLP-76 by ZAP-70 provides an important functional link between the T-cell receptor and activation of ras and calcium pathways.

Adaptor Proteins, Signal Transducing↗

Direct regulation of ZAP-70 by SHP-1 in T cell antigen receptor signaling.

The threshold at which antigen triggers lymphocyte activation is set by the enzymes that regulate tyrosine phosphorylation. Upon T cell activation, the protein tyrosine phosphatase SHP-1 was found to bind to the protein tyrosine kinase ZAP-70. This interaction resulted in an increase in SHP-1 phosphatase activity and a decrease in ZAP-70 kinase activity. Expression of a dominant negative mutant of SHP-1 in T cells increased the sensitivity of the antigen receptor. Thus, SHP-1 functions as a negative regulator of the T cell antigen receptor and in setting the threshold of activation.

Animals↗

SH2 domain function is essential for the role of the Lck tyrosine kinase in T cell receptor signal transduction.

Tyrosine kinase activity is required for signal transduction through the T cell antigen receptor (TCR). The Src family tyrosine kinase Lck appears to play a key role in the initiation of TCR signaling events. We have investigated the role of the phosphotyrosine-binding Src homology-2 (SH2), domain of Lck in TCR signaling. Lck containing a mutation in the phosphotyrosine binding pocket of the SH2 domain was expressed in an Lck-deficient cell line. We found that, in contrast to wild-type Lck, the SH2 domain mutant was unable to restore even the earliest TCR-mediated signaling events. To investigate the role of the Lck SH2 domain, we examined the association of tyrosine phosphoproteins with Lck. The predominant associated phosphoprotein was the ZAP-70 tyrosine kinase, which has also been implicated in the initiation of TCR signaling. In addition, the zeta subunit of the T cell receptor was found to weakly associate with Lck. Further analysis indicated that the SH2 domain of Lck can directly recognize both ZAP-70 and zeta in immunoprecipitates from TCR-stimulated cells. Our findings demonstrate that the SH2 domain of Lck is essential for the initiation of signaling events following TCR stimulation probably as a result of its ability to mediate an interaction between Lck and the ZAP-70 tyrosine kinase and/or the zeta subunit of the T cell receptor.

Calcium↗

Primary B cell lymphoma of the mediastinum.

Primary B cell mediastinal lymphoma has been recognized as a distinct entity recently. This is a retrospective study to define the clinical features and treatment outcome over a 10-year period. Twenty-four consecutive patients (male/female: 11/13) with B cell lymphoma primarily involving the mediastinum were studied. The median age was 34 years. Symptoms were mainly referrable to the chest, with superior vena cava syndrome (SVCO) present in one-third of the patients. Bulky disease was present in over half (58 per cent) and B symptoms were present in 38 per cent of patients. The overall CR rate was 70 per cent and the 5-year OS rates were 56 per cent and 72 per cent for all and CR patients respectively. Five (71 per cent) primary refractory patients and four (66 per cent) relapsed patients died despite salvage therapy. Six relapses occurred at a median of 6 months from treatment. This study showed that primary large B cell lymphoma of the mediastinum is a clinically distinct entity affecting young patients. A significant proportion attained CR and overall, more than half achieved prolonged remission, and most of the relapses occurred early. However, those who failed to attain CR or relapsed still had a poor outcome. An intensive therapy such as autologous bone marrow transplant has to be considered in this subgroup of patients.

Adolescent↗

Risk of further ulcer complications after an episode of peptic ulcer bleeding.

To identify the risk factors for developing recurrent ulcer complications after recovery from an episode of peptic ulcer bleeding 611 patients admitted with peptic ulcer bleeding were studied. Some 557 (91 per cent) were discharged without operation. A total of 22 patients were lost to follow-up and five were excluded as maintenance H2 blockers were required. Of the remaining 530 patients at risk, 169 (32 per cent) developed another complication (166 bleeding, three perforations) over a median follow-up period of 36 months. Patients with duodenal ulcers at the time of bleeding, previous history of peptic ulcer, previous bleeding, history of dyspepsia longer than 3 months, and a short interval between previous ulcer complications and the index bleed were more likely to develop further complications. Sex, age, smoking, coexisting illness, non-steroidal anti-inflammatory drugs intake and time taken to achieve ulcer healing had no predictive value.

Adolescent↗

Through-the-scope balloon dilation for pyloric stenosis: long-term results.

BACKGROUND: Through-the-scope balloon dilation has been used for treatment of benign pyloric stenosis; however, long-term results are lacking in the literature. METHOD: A retrospective analysis using the Kaplan-Meier method. RESULTS: Between November 1986 and December 1993, 54 patients underwent through-the-scope balloon dilations for pyloric stenosis. The mean age was 57.5 years. There were 5 (9.3%) initial treatment failures due to tight stenoses and perforations from dilation occurred in 4(7.4%) patients. Forty-five (83.3%) patients underwent successful dilation. Four patients developed rapid restenoses and were found to have malignant obstructions. Forty-one patients entered our study. Time at risk commenced on the date of initial dilation. The end point was defined at the time at which patients presented with recurrent obstruction or other ulcer complications. The median follow-up period was 39 months. The ulcer complication-free probability at 3 months, and at 1, 2, and 3 years was 79.1%, 73.4%, 69.3%, and 54.7%, respectively. In all, 21 (51.2%) patients required subsequent surgery: 18 for recurrent obstructions, 2 for interval perforations, and 1 for bleeding. CONCLUSION: While through-the-scope balloon dilation may palliate symptoms of obstruction, recurrent obstruction and other ulcer complications are common. It should be reserved only for patients at high risk for operative surgery.

Adult↗

Epinephrine or epinephrine plus alcohol for injection of bleeding ulcers: a prospective randomized trial.

BACKGROUND: Rebleeding following epinephrine injection of bleeding peptic ulcers occurs in 10% to 20% of all cases. The addition of a sclerosant has the theoretical advantage of inducing vessel thrombosis and permanent hemostasis. METHODS: A prospective randomized controlled trial was conducted to compare injections with epinephrine alone or epinephrine plus absolute alcohol in patients with actively bleeding ulcers at endoscopy. Repeat endoscopy was performed 24 hours later; treatment was repeated in the presence of endoscopic signs of rebleeding. Surgery was performed when arterial bleeding could not be controlled endoscopically, clinical rebleeding with hematemesis or shock occurred, or the transfusion total exceeded 8 units. RESULTS: One hundred sixty patients were enrolled (epinephrine alone, 81; epinephrine and absolute alcohol, 79). They were matched in age, sex, location of ulcers, hemoglobin on admission, shock, and severity of bleeding. Initial hemostasis was comparable: 79 of 81 with epinephrine alone (97.5%) versus 75 of 79 with epinephrine and absolute alcohol (94.9%). No difference was observed between the two with respect to either rebleeding (9 vs 6), need for emergency operation (12 vs 9), transfusion requirement (median, three units vs two units), hospital stay (median, 5 days vs 4 days), mortality (4 vs 7) and ulcer healing at 4 weeks (50 vs 46). CONCLUSIONS: The additional injection of absolute alcohol after endoscopic epinephrine injection confers no advantage.

Adolescent↗

Selective use of preoperative endoscopic retrograde cholangiopancreatography in laparoscopic cholecystectomy.

BACKGROUND: The management of possible common bile duct (CBD) stones in patients scheduled for laparoscopic cholecystectomy remains controversial. METHODS: Prospective evaluation of 609 patients who underwent laparoscopic cholecystectomy was carried out in relation to the use of selective preoperative ERCP for detection of common duct stones. Preoperative ERCP was performed if there is or has been (1) cholangitis, biliary pancreatitis, or jaundice; (2) abnormal serum liver tests or (3) ultrasonogram showing a dilated CBD or ductal stones. RESULTS: A total of 139 patients underwent preoperative ERCP, and cannulation of CBD was successful in 133 patients (96%). CBD stones were found in 60 patients (45%) and extracted after sphincterotomy. High prevalence of CBD stones was noted in patients with acute cholangitis and CBD stones on ultrasonogram. There were six endoscopic sphincterotomy-related complications (complication rate, 4.5%): bleeding (2), pancreatitis (3), retroduodenal perforation (1). No patient required surgery as the result of a complication. The prediction of the occurrence of ductal stones was further analyzed using stepwise logistic regression. Acute cholangitis and CBD stones on ultrasonogram were shown to be independent significant risk factors with odds ratios of 8.9 and 13.5, respectively. CONCLUSIONS: With selective preoperative ERCP, suspected CBD stones can be identified and removed prior to laparoscopic cholecystectomy.

Adult↗