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Biomedical subjects

S W Chung

Publications and source records attributed to S W Chung.

At least 55 records · Page 3Linked to original sources
PubMed1999

Racial differences between solid organ transplant donors and recipients in British Columbia: a five-year retrospective analysis.

BACKGROUND: We attempted to determine whether significant racial differences exist between organ donors and transplant recipients in British Columbia, and whether differences exist between individual organ transplant programs (lung, heart, kidney, liver, and pancreas). The design of the study was a retrospective review. METHODS: We used the database of the British Columbia Transplant Society, a provincial agency, for the years 1992 to 1997 inclusive. The outcome measures were a comparison of racial characteristics of organ donors and transplant recipients collectively and by individual organ transplant program. RESULTS: There were 236 organ donors and 766 transplant recipients. Comparing racial groups between donors and recipients, Caucasians contributed the most donors (93.2%) but received proportionately fewer organs (73.4%, P<0.000001). Orientals donated 3.4% of all organs but constituted 14.4% of all recipients (P<0.00001). Non-Oriental, non-Caucasians (predominantly Asian Indians and Native Aboriginals) constituted 3.4% of all donors and 12.2% of all recipients (P=0.0001). Among the individual organ transplant programs, lung, heart, and pancreas recipients were predominantly Caucasian (148 of 156 recipients). Oriental recipients were more likely to be kidney recipients (19.8% of all kidney recipients) compared with all Oriental recipients (P<0.000001). Likewise, Asian Indians were more likely to be kidney recipients (7.2% of all kidney recipients) compared with all Asian Indian recipients (P<0.0001). Native Aboriginals, however, were more likely to be liver allograft recipients (8.3% of all liver transplants) than nonliver allograft recipients (P=0.017). CONCLUSIONS: In British Columbia, disparity exists between Oriental and non-Oriental, non-Caucasian donors and recipients. Orientals and Asian Indians were more likely to be kidney graft recipients than nonkidney graft recipients, whereas Native Aboriginal recipients seemed more likely to have undergone liver transplantation.

Asian People↗
PubMed1999

Retinoids inhibit interleukin-12 production in macrophages through physical associations of retinoid X receptor and NFkappaB.

Lipopolysaccharide (LPS) increases the production of interleukin-12 (IL-12) from mouse macrophages via a kappaB site within the IL-12 p40 promoter. In this study, we found that retinoids inhibit this LPS-stimulated production of IL-12 in a dose-dependent manner. The NFkappaB components p50 and p65 bound retinoid X receptor (RXR) in a ligand-independent manner in vitro, and the interaction interfaces involved the p50 residues 1-245, the p65 residues 194-441, and the N-terminal A/B/C domains of RXR. Activation of macrophages by LPS resulted in markedly enhanced binding activities to the kappaB site, which significantly decreased upon addition of retinoids, as demonstrated by the electrophoretic mobility shift assays. In cotransfections of CV-1 and HeLa cells, RXR also inhibited the NFkappaB transactivation in a ligand-dependent manner, whereas a mutant RXR lacking the AF2 transactivation domain, which serves as ligand-dependent binding sites for transcription integrators SRC-1 and p300, was without any effect. In addition, coexpression of increasing amounts of SRC-1 or p300 relieved the retinoid-mediated inhibition of the NFkappaB transactivation. From these results, we propose that retinoid-mediated suppression of the IL-12 production from LPS-activated macrophages may involve both inhibition of the NFkappaB-DNA interactions and competitive recruitment of transcription integrators between NFkappaB and RXR.

Animals↗
PubMed1999

Liver transplantation for chronic hepatitis B infection with the use of combination lamivudine and low-dose hepatitis B immune globulin.

Current protocols for prophylaxis against allograft reinfection after liver transplantation for chronic hepatitis B virus (HBV) infection include the administration of large doses of hepatitis B immune globulin (HBIG), with considerable associated economic costs. Monotherapeutic prophylaxis with lamivudine has been complicated by the development of resistant strains of HBV. We studied the effectiveness of a posttransplantation prophylaxis protocol using combination lamivudine and low-dose HBIG in 7 consecutive patients with chronic HBV infection, 4 of whom were serum HBV DNA positive before pretransplantation lamivudine therapy. All patients were serum HBV DNA negative at transplantation and received lamivudine, 100 mg/d, posttransplantation. HBIG, 2170 IU, was administered intramuscularly intraoperatively and daily for 14 days. Maintenance HBIG therapy consisted of 2170 IU intramuscularly twice weekly, tapered to every 2 to 4 weeks by 12 months posttransplantation. Target serum HBIG (HBV surface antibody) titers were less than 500 IU/L for 6 months, then greater than 300 IU/L until 12 months posttransplantation. Induction serum HBIG titers were determined daily in 5 patients, and both serum HBIG and hepatitis B surface antigen were determined every 4 weeks in all patients. One patient died 61 days posttransplantation; the surviving patients (n = 6) were followed up for a mean of 532 days (range, 395 to 648 days). No patient has developed allograft reinfection. In the induction period, a target HBIG titer of greater than 500 IU/L was not achieved until a mean of 6.8 days (range, 5 to 10 days). In the maintenance period, all patients achieved the target HBIG titer. This suggests combination lamivudine and low-dose HBIG is effective in preventing allograft reinfection by HBV.

Follow-Up Studies↗
PubMed1999

A rapid restriction fragment length polymorphism polymerase chain reaction-based diagnostic method for identification of T-cell lymphoproliferative disorders.

BACKGROUND: Identification of a clonal proliferation of lymphocytes is central to the diagnosis of lymphoma compared with a reactive lymphoproliferation. We propose a novel diagnostic technique based on restriction fragment length polymorphism (RFLP) of amplified polymerase chain reaction (PCR) products of the T-cell receptor -gamma (TCR-gamma) gene rearrangement to rapidly identify monoclonality in T-cell lymphomas and improve diagnosis of malignancy. MATERIALS AND METHODS: DNA from peripheral blood mononuclear cells (PBMCs) of 10 healthy volunteers and 7 T-cell lymphoma patients were isolated and the TCR-gamma was amplified with consensus primers for the different variable (V) and joining (J) segments. Restriction digests were done using BstN1 and the fragments separated via gel electrophoresis. Verification was by Southern analysis. RESULTS: Restriction digests of the 10 healthy controls show a characteristic nine-band digest pattern whereas the restriction digests of the 7 T-cell lymphomas each show altered banding patterns completely distinct from the normal nine-band pattern (Fisher exact test = 0.00005). Sensitivity assays demonstrate the test can detect clonal populations representing 2% of total. This method also enables identification of particular clonal populations. The entire procedure can be performed in one day, does not require radioactivity, and requires only small quantities of specimens. CONCLUSIONS: This RFLP-PCR-based diagnostic method for T-cell lymphomas is specific, sensitive, efficient, and reproducible, and enables the identification of clonally expanded populations of T lymphocytes. It offers the ability to identify particular clonal populations, as with Southern analysis, combined with the benefits of a PCR method.

Blotting, Southern↗
PubMed1999

Radiofrequency ablation followed by resection of malignant liver tumors.

BACKGROUND: Radiofrequency ablation (RFA) has recently been used to treat liver tumors, but few clinical reports have described the pathological characteristics of radiofrequency ablation in human specimens. This study delineates the gross pathologic and histochemical changes induced by RFA in benign and malignant human liver tissue and confirms the tumor necrosis described in early clinical reports. METHODS: Ten patients with metastatic tumors of the liver received a single treatment of ultrasound-guided percutaneous RFA to 12 tumors. Hepatic resection was carried out within 6 weeks of RFA. Specimens were stained with standard hematoxylin and eosin stain followed by oxidative stain to determine if there was evidence of viable tumor within the zone of ablation. RESULTS: Nine of the 12 ablations were resected. Microscopic examination within the zone of ablation showed successful ablation in 8 of the 9 resected ablations. CONCLUSIONS: Percutaneous RFA creates well-circumscribed areas of tumor necrosis with apparent cell death using an oxidative stain. Further investigation is encouraged to determine the clinical effectiveness of radiofrequency ablation in the complete destruction of liver tumors for palliative or curative intent.

Aged↗
PubMed1999

Interleukin-12-secreting fibroblasts are more efficient than free recombinant interleukin-12 in inducing the persistent resistance to Mycobacterium avium complex infection.

To determine whether the paracrine secretion of interleukin-12 (IL-12) can efficiently stimulate the resistance to Mycobacterium avium complex (MAC) infection, 3T3 fibroblasts were stably transfected to secrete IL-12 (480 U/106 cells/48 hr) and their effect on MAC infection was investigated in genetically susceptible BALB/c mice, compared with that of free recombinant IL-12 (rIL-12). Injection with IL-12-secreting fibroblasts (3T3-IL-12) during intranasal infection with MAC resulted in a significant decrease in the bacterial load of the lung during the entire 10-week observation period, while rIL-12 reduced the bacterial load initially, at 2 weeks, but not by 10 weeks postinfection. Lung CD4+ T cells in mice injected with the 3T3-IL-12 cells showed a persistent T helper type 1 (Th1) response throughout the 10-week period. Furthermore, immunization with the 3T3-IL-12 cells induced and maintained significantly higher levels of cytotoxic activity and nitric oxide production by lung cells than did rIL-12 immunization. This work suggests that IL-12-secreting fibroblasts may serve as a vehicle for paracrine secretion of IL-12 for immunotherapy of MAC infection.

Animals↗
PubMed1999

Sulfasalazine prevents T-helper 1 immune response by suppressing interleukin-12 production in macrophages.

Interleukin-12 (IL-12) plays a pivotal role in the development of T-helper 1 (Th1) immune response, which may be involved in the pathogenesis of chronic inflammatory autoimmune disorders. In this study we investigated the effects of sulfasalazine, a drug for treating inflammatory bowel disease and rheumatoid arthritis, on the production of IL-12 from mouse macrophages stimulated with lipopolysaccharide (LPS). Sulfasalazine potently inhibited the production of IL-12 in a dose-dependent manner, in part through the down-regulation of nuclear factor kappaB (NFkappaB) activation in IL-12 p40 gene. Activation of macrophages by LPS resulted in markedly enhanced binding activities to the kappaB site, which significantly decreased upon addition of sulfasalazine as demonstrated by an electrophoretic gel shift assay. Importantly, macrophages pretreated with sulfasalazine either in vitro or in vivo reduced their ability to induce interferon-gamma (IFN-gamma) and increased the ability to induce IL-4 in antigen-primed CD4+ T cells. From these results, sulfasalazine may induce the Th2 cytokine profile in CD4+ T cells by suppressing IL-12 production in macrophages, and sulfasalazine-induced inhibition of IL-12 production in macrophages may explain some of the known biological effects of sulfasalazine.

Animals↗
PubMed1999

Chemo-embolization of hepatic tumours.

Over the past decade, increasing use of chemo-embolization with chemotherapeutic agents emulsified in oil has been made in the treatment of both primary and metastatic liver tumours. These lesions are often not amenable to surgical resection and are not responsive to systemic chemotherapy. Chemo-embolization provides an additional therapeutic option which, in some instances, can provide significant benefit. This pictorial review discusses the technique of chemo-embolization, as well as aspects of patient selection, complications, and tumour response.

Carcinoma, Hepatocellular↗
PubMed1999

Assessment of immunologic status of liver transplant recipients by peripheral blood mononuclear cells in response to stimulation by donor alloantigen.

OBJECTIVE: To determine whether there is a role for assessing peripheral blood mononuclear cell (PBMC) cytokine patterns as a means of measuring the immunologic and clinical status of liver transplant recipients. SUMMARY BACKGROUND DATA: The role of assessing cytokine patterns in the prediction of clinical graft rejection or acceptance remains unclear. The purpose of this study was to examine the cytokine profiles of PBMC stimulated in vitro with donor alloantigen and to correlate prospectively the data with clinical assessment of graft status in orthotopic liver transplant (OLT) recipients. METHODS: PBMCs from OLT recipients were examined for proliferation and cytokine mRNA expression after stimulation by donor alloantigen, third-party alloantigen, or phytohemagglutinin (PHA). mRNA extracted from PBMC was amplified by reverse transcriptase-polymerase chain reaction with oligospecific primer pairs for interleukin (IL)-2, IL-4, IL-6, IL-10, interferon (IFN) gamma, tumor necrosis factor (TNF) alpha and transforming growth factor (TGF) beta. Results were prospectively correlated with each patient's allograft status. RESULTS: Increased IL-4 and TGF-beta and decreased IL-2, IFNgamma, and TNF-alpha mRNA expression by PBMCs in response to donor alloantigen stimulation predicted immunologic graft stability over a minimum 60-day interval compared with mRNA expression of PBMCs from patients with established rejection or those who experienced a rejection episode within a 30-day period (p < 0.05). Stimulation of recipient PBMCs with third-party alloantigens or PHA yielded similar but less specific results. PBMC proliferation to varying antigenic stimulation did not correlate with clinical graft status, nor did cytokine production by unstimulated PBMC. CONCLUSIONS: Prospective assessment of cytokine expression by PBMC from OLT recipients in response to stimulation by donor alloantigen is helpful for predicting the clinical status of the allograft and may be useful in the development of more precise immunologic monitoring protocols.

Adult↗
PubMed1999

Post-surgical shunt hepatopulmonary syndrome in a case of non-cirrhotic portal hypertension: lack of efficacy of shunt reversal.

Hepatopulmonary syndrome, a consequence of significant liver disease and portal hypertension, is thought to be secondary to the effects of vasoactive substances, normally inactivated in the liver, on the pulmonary vasculature. We report a patient with preserved hepatic function who underwent a decompressive surgical porto-systemic shunt for non-cirrhotic portal hypertension. This patient developed hepatopulmonary syndrome with dyspnoea and oxygen desaturation 2 years post-surgical shunt. Over the next 7 years, the patient's respiratory function became increasingly impaired although hepatic function remained preserved. Because of the hypothesized role of porto-systemic shunting in the aetiology of this syndrome, the surgical shunt was successfully reversed angiographically. No improvement in dyspnoea or oxygen saturation occurred and liver transplantation was undertaken. Six months post-transplant, the patient has decreased his oxygen requirements and is free of dyspnoea. Our experience supports the causal role of porto-systemic shunting in the pathogenesis of hepatopulmonary syndrome but suggests that merely decreasing the extent of porto-systemic shunting is not beneficial. Liver transplantation remains the only reliable therapeutic modality available to these patients.

Adult↗
PubMed1999

Spontaneous patterning of quantum dots at the air-water interface.

Nanoparticles deposited at the air-water interface are observed to form circular domains at low density and stripes at higher density. We interpret these patterns as equilibrium phenomena produced by a competition between an attraction and a longer-ranged repulsion. Computer simulations of a generic pair potential with attractive and repulsive parts of this kind, reproduce both the circular and stripe patterns. Such patterns have a potential use in nanoelectronic applications.

Journal Article↗
PubMed1998

Involvement of C-Abl tyrosine kinase in lipopolysaccharide-induced macrophage activation.

LPS endotoxin-induced macrophage activation is recognized to be important in both nonspecific immunity and endotoxin-induced sepsis when excessive macrophage stimulation occurs. In this study, we showed that reduction of c-Abl in macrophages prevented LPS-induced growth arrest, nitric oxide production and TNF-alpha secretion by ANA-1 macrophages. These cells continued to grow but later underwent apoptosis. Reduction of c-Abl in these cells led to reduced c-Abl kinase activity associated with Ran, which recently has been shown to be an LPS-responsive gene product. Our data suggest that c-Abl tyrosine kinase is one of the intermediates downstream of the initial signal transduction event related to activation of macrophages by LPS.

Animals↗
PubMed1998

Donor-specific stimulation of peripheral blood mononuclear cells from recipients of orthotopic liver transplants is associated, in the absence of rejection, with type-2 cytokine production.

In this study, we examined the cytokine production by human peripheral blood mononuclear cells (PBM) from recipients of orthotopic liver transplants which had been stimulated by donor-specific alloantigen. Levels of interleukin (IL)-2, IL-4, interferon (IFN)-gamma, IL-10 and transforming growth factor (TGF)-beta produced in vitro from PBM of 15 transplant recipients at 5-7 months post transplantation were analysed after donor-specific, third-party, or non-specific stimulation. Mononuclear cell proliferation in response to stimulation and cytokine mRNA from the cell cultures were assayed. Donor-specific antigen was obtained from donor spleen cells which had been obtained and frozen in liquid nitrogen at the time of organ retrieval. Third-party restimulation used equivalent numbers of spleen cells pooled from the other 14 organ donors. Cytokine production was correlated with the clinical condition of the patient, including biopsy results when available, and biochemical data. The data show a highly significant correlation between the donor-specific- and third-party- stimulated IL-4 and IL-10 production from recipient PBM with stable liver graft function as assessed by histopathology and/or biochemistry. This correlation was independent of level of immunosuppression. These data strongly support a role for IL-4 and/or IL-10 in the induction and/or maintenance of tolerance to human liver allografts. Measurement of the levels of these cytokines from recipient PBM after donor-specific antigen stimulation in vitro may be a useful test for monitoring for acute allograft rejection.

Adjuvants, Immunologic↗
PubMed1998

TCR diversity in gammadeltaTCR+ hybridomas derived from mice given portal vein donor-specific pre-immunization and skin allografts.

Portal venous (p.v.) immunization with multiple minor histoincompatible cells leads to antigen-specific increased skin allograft survival. GammadeltaTCR+ hybridoma cells, prepared from mesenteric lymphocytes of p.v. immunized animals, can adoptively transfer this increased graft survival to naive animals. We have analyzed VgammaVdelta gene usage, and TCR gamma-chain junctional diversity in gammadeltaTCR+ hybridomas from mice immunized with different antigen combinations by p.v. or conventional lateral tail vein (i.v.) immunization. Following p.v. immunization two independent sets of hybridoma cells were derived, one expressing a common gamma-chain junctional sequence which was also found in > 85% of the hybridomas derived following i.v. immunization, while the other set showed remarkable gamma-chain junctional sequence diversity. The diversity seen in these latter hybridomas was associated with the antigen specificity of the hybridoma cells. Cells expressing these 'unique' TCR junctional sequences were stimulated to produce cytokines both by hsp and by minor-histocompatibility-specific irradiated peritoneal cells. Cells expressing TCR with a common gamma-chain junctional sequence were stimulated to cytokine production by MHC-matched but minor-histocompatibility mismatched (as well as matched) peritoneal cells, but not by hsp. We suggest that p.v. immunization results in stimulation of both antigen-specific and non-specific regulatory gammadeltaTCR+ cells, which can be distinguished by gamma-chain TCR sequence diversity.

Adoptive Transfer↗
PubMed1998

Primary induction with mycophenolate mofetil and corticosteroids in a liver transplant recipient with hepatorenal syndrome.

OBJECTIVE: To report the use of mycophenolate mofetil for primary induction in a liver transplant recipient to avoid the nephrotoxicity of cyclosporine/tacrolimus. CASE SUMMARY: A 47-year-old white man in a hepatic coma with anuric hepatorenal syndrome received a liver transplant, and was given mycophenolate mofetil and corticosteroids as primary induction immunosuppression with the addition of low-dose cyclosporine 13 days later. His renal function improved and he remains rejection-free after 13 months of follow-up. CONCLUSIONS: This case suggests that mycophenolate mofetil may be used as a primary induction agent in liver transplant recipients with renal failure to avoid the additional nephrotoxicity of the standard immunosuppressants, cyclosporine and tacrolimus. Low-dose cyclosporine/tacrolimus may be introduced later as the renal function improves.

Hepatic Encephalopathy↗
PubMed1998

Surgical staplers for vascular control of hepatic veins and portal structures in major hepatic resection.

Phenomenal progress has occurred in the art of liver resection. Only a decade ago massive blood transfusion, liver failure, bile leak, or sepsis were alI frequent attendants of major resection, and intraoperative death from torrential bleeding from hepatic veins or vena cava was not uncommon. Now, major liver resection may be accomplished routinely without blood transfusion, and operative mortality of 0% to 2% is standard in expert hands. Uncontrolled hemorrhage remains the primary cause of intraoperative death. Mortality in the early postoperative period is usually related to delayed hemorrhage, inadequate hepatic reserve, or injury to vital blood supply or biliary drainage in the liver remnant.

Journal Article↗