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Biomedical subjects

T M Chan

Publications and source records attributed to T M Chan.

At least 37 records · Page 2Linked to original sources
PubMed2003

The pathogenetic role of immunoglobulin G from patients with systemic lupus erythematosus in the development of lupus pleuritis.

OBJECTIVE: To investigate the pathophysiological effect of immunoglobulin G (IgG) from systemic lupus erythematosus (SLE) patients on pleural mesothelial cells and related mechanisms. METHODS: Serum IgG from 28 lupus patients and 13 healthy controls was purified by protein-G affinity chromatography. The concentrations of anti-dsDNA-, anti-histone- and/or anti-nucleohistone-containing IgGs were determined by enzyme-linked immunosorbent assay (ELISA). Lupus patients were divided into an active (n = 12) and an inactive group (n = 16) on the basis of the SLE Disease Activity Index (SLEDAI). The binding of IgG to a human pleural mesothelial cell line (MeT-5A) under different conditions, including pretreatment with DNase and preincubation with exogenous histone, DNA or nucleohistone, was examined using flow cytometry and cellular ELISA. The effect of IgG on MeT-5A cell proliferation was studied using an MTT assay. Gene expression and protein synthesis for interleukin 1beta (IL-1beta), monocyte chemoattractant protein 1 (MCP-1) and transforming growth factor beta1 (TGF-beta1) in MeT-5A cells were determined using reverse transcription-polymerase chain reaction and ELISA. RESULTS: The binding of IgG to MeT-5A cells was higher in the active lupus group than the inactive lupus group (P = 0.047) and controls (P = 0.003). The binding decreased in both lupus groups following pretreatment of MeT-5A cells with DNase. The binding of IgG to MeT-5A cells was greater by 112% in the active lupus group after preincubation with histone (P < 0.001), but not with DNA or nucleohistone. Exposure of MeT-5A cells to IgG from either lupus group induced cell proliferation when compared with IgG from healthy controls (P = 0.04). Gene expression and protein synthesis of MCP-1, TGF-beta1 and IL-1beta in MeT-5A cells were significantly increased after incubation with IgG from patients with active lupus when compared with IgG from the inactive lupus and control groups (P < 0.01). The concentration of anti-dsDNA antibodies correlated with the binding of IgG to MeT-5A cells and the synthesis of cytokines by MeT-5A cells. The serum level of anti-histone antibodies in the active lupus group was higher than that in the inactive group (P = 0.015) and the serum concentration correlated with cell binding and MCP-1 production. CONCLUSIONS: IgG from lupus patients can bind to MeT-5A cells and the binding is modulated by DNA or histone. Binding of anti-dsDNA-containing IgG to MeT-5A cells induces the synthesis of proinflammatory cytokines. Our findings suggest that the binding of anti-dsDNA antibodies, particularly the IgG isotype, to pleural mesothelium plays a direct pathogenetic role in inducing inflammatory injury in the serositis of SLE.

Acute Disease↗
PubMed2003

Subgingival microbiota of renal transplant recipients.

Renal transplant patients undergoing immunosuppressive therapy may experience periodontal side-effects such as gingival overgrowth. This study evaluated the subgingival microbiota of renal transplant recipients with or without periodontal tissue destruction who may have concurrent gingival enlargement. Subgingival paper point samples taken from the deepest probing sites of 38 subjects (one per patient) were examined using direct microscopy and culture techniques. A complex microflora comprising gram-positive and gram-negative cocci, rods and filaments, fusiforms, curved rods and spirochetes was observed using microscopy. Yeasts were occasionally detected. Significantly higher proportions of gram-positive morphotypes, including gram-positive cocci, were observed in samples from periodontally healthy patients. The predominant cultivable microflora from anaerobic culture comprised several species of facultative and obligate anaerobes. Colonization of the subgingival sites by 'foreign' microbes that are normally dermal, intestinal or vaginal flora was detected in up to 50% of the samples. High mean proportions of lost or unidentified species were also occasionally noted. The results showed that the subgingival biofilm of renal transplant recipients with chronic periodontitis comprised mainly gram-negative rods and spirochetes. Besides the usual predominant cultivable subgingival microbiota associated with periodontitis, the high prevalence of unidentified and 'foreign' microbes indicates the possibility of subgingival microbial alteration in renal transplant patients.

Adult↗
PubMed2003

Burkholderia urinary tract infection after renal transplantation.

Urinary tract infection is a common complication after renal transplantation. The etiologies are diverse and the bacterial agents may sometimes be acquired during the hospital stay. We report a patient who developed Burkholderia cepacia urinary tract infection after renal transplantation. The bacteria showed in vivo resistance to all of the available antibiotics. A graft nephrectomy was eventually required to clear the infection. The consequence of some fastidious infection may be catastrophic and early recognition and treatment is necessary to optimize the treatment.

Burkholderia Infections↗
PubMed2003

Disseminated ochroconis gallopavum infection in a renal transplant recipient: the first reported case and a review of the literature.

Ochroconis gallopavum is a potentially fatal dematiaceous fungus causing opportunistic infections in immunocompromised hosts. We report the first case of disseminated O. gallopavum infection in a 13-year-old renal transplant recipient, which involved the brain, lung and spleen. He was treated with amphotericin B, itraconazole and voriconazole, a new antifungal agent first used to treat such an infection. Besides antifungal treatment, all immunosuppressive agents were stopped and automated peritoneal dialysis was resumed. The initial infection was under control with both clinical and radiological improvements after treatment. However, the patient later acquired Acremonium spp. peritonitis; he failed to respond to high-dose amphotericin B, and finally succumbed. A total of 13 reported O. gallopavum human infections, including the one described here, are reviewed. The most common site of involvement is the brain and the crude mortality rate is up to 46%. As the disease is potentially lethal in immunocompromised hosts, empirical antifungal coverage should be considered in post-renal transplant recipients with suspected brain abscess. Early biopsy of lesion for histopathological and microbiological diagnosis would be essential in managing such cases.

Adolescent↗
PubMed2002

Combination gemcitabine and cisplatin chemotherapy for metastatic or recurrent nasopharyngeal carcinoma: report of a phase II study.

BACKGROUND: To evaluate the efficacy and toxicity of combination gemcitabine plus cisplatin (GC) chemotherapy in metastatic or recurrent nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: Forty-four patients of Chinese ethnicity with metastatic or recurrent NPC received ambulatory GC chemotherapy every 28 days (gemcitabine 1000 mg/m(2) days 1, 8 and 15; cisplatin 50 mg/m(2) days 1 and 8). There were 40 male and four female patients with a mean age of 47.4 years. More than half (54.5%) of the patients had received either prior platinum-based chemotherapy and/or radiotherapy to target lesions. RESULTS: There were nine complete responses and 23 partial responses in the 44 patients, achieving an overall response rate of 73% (78% for the 41 assessable patients). The mean duration of response was 5.3 months. Improved subjective symptom-control scores were found in 78% of patients with pre-existing symptoms, while 64% of patients experienced improved general well-being scores. Toxicity was mainly hematological: grade III/IV anemia, granulocytopenia and thrombocytopenia were found in 11, 37 and 16% of cycles, respectively. With a median follow-up of 17.2 months, 62% survived 1 year while 36% were alive and progression free. CONCLUSIONS: Gemcitabine plus cisplatin chemotherapy offers a satisfactory overall response rate, subjective patient improvement and safety profile for metastatic and recurrent NPC.

Adenocarcinoma↗
PubMed2002

Effect of mycophenolate mofetil on severity of nephritis and nitric oxide production in lupus-prone MRL/lpr mice.

Mycophenolate mofetil (MMF), an immunosuppressive drug commonly used in organ transplantation, is increasingly being used to treat autoimmune diseases including systemic lupus erythematosus (SLE). Excessive production of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) has been implicated in the pathogenesis of lupus nephritis. We evaluated the effect of MMF on the severity of nephritis and the production of NO in lupus-prone MRL/lpr mice. Eight-week-old female MRL/lpr mice (n = 20) were treated with MMF (100 mg/kg/day) by oral gavage for 12 weeks. Control mice (n = 20) received vehicle on the same schedule. The mice were killed after 12 weeks of treatment. Treatment with MMF significantly decreased the amount of proteinuria, prolonged survival and reduced the histological severity of glomerulonephritis. Urinary nitrite/nitrate excretion in the MMF-treated mice was significantly reduced during the first 8 weeks of treatment. However, by the end of the 12 weeks' treatment period, there was no significant difference between vehicle and MMF-treated mice in terms of urinary nitrite/nitrate excretion, intra-renal production of NO, expression of iNOS protein and induction of iNOS mRNA. We conclude that MMF is effective in attenuating the severity of nephritis in MRL/lpr mice. The beneficial effects of MMF on lupus nephritis during the early phase of the disease might be partly attributed to the inhibition of NO production. The inhibitory effect of MMF on NO production diminishes as the disease progresses. MMF probably has additional, as yet undefined mode of actions to fully account for its beneficial effects on lupus nephritis.

Animals↗
PubMed2001

Nosocomial outbreak of parvovirus B19 infection in a renal transplant unit.

BACKGROUND: Parvovirus B19 (B19) infection is known to cause chronic infection leading to anemia in immunocompromised patients. Although nosocomial B19 infections in immunocompetent patients have been documented, no outbreaks in immunocompromised patients have been previously reported. Whether transmission can occur from a patient with chronic infection is also unknown. METHODS: An outbreak of B19 infection in a renal transplant unit was investigated by molecular analysis of the virus strains and a case-control study. RESULTS: Three patients had genetically identical virus strains suggesting the occurrence of nosocomial transmission. The index case transmitted infection many weeks after the onset of her clinical symptoms. Other patients at risk of acquiring infection were those most intensively immunosuppressed. Viral load in the serum correlated with the hematological response. A rebound in the viral load was associated with clinical relapse and the failure of i.v. immunoglobulin therapy. CONCLUSION: Nosocomial transmission of B19 can occur from immunocompromised patients even when they are in the chronic stage of the infection. The clinical and virological response to i.v. immunoglobulin therapy is variable and depends on the overall level of immunosuppression of the patient.

Adult↗
PubMed2001

Increased survival of mesothelial cells from the peritoneum in peritoneal dialysis fluid.

Peritonitis remains the most important factor in patient morbidity and technical failure associated with continuous ambulatory peritoneal dialysis (CAPD). In vitro examination of bacterial infection of cultured human peritoneal mesothelial cells (HPMC) is an attractive approach to the study of peritonitis in CAPD, yet there are few reports on this subject. Previous studies have shown two limitations: (i) cell cultures of HPMC lasted for days only when incubated in culture medium and (ii) short-term studies of <30 min were done in HPMC when incubated with peritoneal dialysis fluid (PDF). Human peritoneal mesothelial cells, maintained in a conventional single chamber culture system with PDF alone, were unable to survive more than 40 min. The present study was designed to prolong the viability of HPMC cultured in PDF, with the object of using cells under different conditions, such as that of simulating CAPD. HPMC were cultured using plastic microtiter plates, where they were grown to confluence and growth was arrested. PDF containing different concentrations of NaHCO3and human serum albumin was added. Cell viability after exposure for up to 24 h was measured by trypan blue, Cell Death Detection ELISA and Annex-V flow cytometry. The data confirmed the 'toxic' effect of PDF, with cell viability being <40% after 2 h incubation in 4.25% glucose in PDF. However, the survival time of HPMC increased significantly in 4.25% glucose PDF at a physiological pH and even further after the addition of human albumin. These experimental conditions simulating CAPD may allow future in vitro studies of mesothelial physiology and peritonitis related to CAPD treatment.

Cell Culture Techniques↗
PubMed2001

Structural characterization of the oxidative degradation products of an antifungal agent SCH 56592 by LC-NMR and LC-MS.

LC-NMR and LC-MS were used to characterize the structures of four major degradation products of SCH 56592, an antifungal drug candidate in clinical trials. These compounds were formed under stress conditions in which the bulk drug substance was heated in air at 150 degrees C for 12 days, and were separated from SCH 56592 as a mixture using a semi-preparative HPLC method. The data from LC-NMR, LC-ESI-MS (electrospray ionization mass spectrometry) and LC-ESI-MS/MS indicate that the oxidation occurred at the piperazine ring in the center of the drug molecule. The structures of the degradation products were determined from the 1H NMR spectra obtained via LC-NMR, which were supported by LC-ESI-MS and LC-ESI-MS/MS analyses. A novel degradation pathway of SCH 56592 was proposed based on these characterized structures.

Antifungal Agents↗
PubMed2001

Identification of polyamides that enhance adenovirus-mediated gene expression in the urothelium.

Adenovirus-mediated gene therapy of bladder diseases has been limited by the inability to transduce the urothelium successfully using adenoviral vectors. We have sought to identify agents that would increase adenovirus-mediated transgene expression in the bladder. We have utilized a rat model to screen compounds for their ability to enhance viral transgene expression in the rat bladder. Rats received intravesical administration of replication-deficient adenovirus (rAd) formulated in various agents, and transgene expression was evaluated after 48 h by determining the amount of lacZ expression in the luminal epithelium of the bladder. We report the identification of two different polyamides, each capable of dramatically increasing viral transgene expression in the bladder without causing detectable alteration of the umbrella cell layer of the urothelium. We have utilized a carcinogen-induced rat bladder tumor model to demonstrate that these polyamides are also capable of enhancing viral transgene expression in tumor tissue. The identification of these polyamides potentiates the use of adenovirus-mediated gene therapy for the treatment of superficial bladder cancer or other bladder diseases.

Adenoviridae↗
PubMed2001

Acute pancreatitis complicating acute exacerbation of chronic hepatitis B infection carries a poor prognosis.

The clinical outcome of acute pancreatitis complicating acute exacerbation of chronic hepatitis virus B (HBV) infection has never been studied. Ninety patients with acute pancreatitis were recruited. Five patients (5.6%) (Group 1) had acute pancreatitis superimposed on acute exacerbation of chronic HBV infection with no other causes of acute pancreatitis being identified. The clinical outcome of these five patients was compared to the 85 non-HBV infected patients (Group 2) with acute pancreatitis. A third group (Group 3) of patients (n=406) with acute exacerbation of chronic HBV infections without acute pancreatitis was also recruited for comparison. Group 1 had a significantly higher mortality rate (4 out of 5, 80%) compared to those of Group 2 (13 out of 85, 15.3%, P=0.0041) and Group 3 (9 out of 406, 2.2%, P < 0.0001). In Group 1 patients, the acute pancreatitis occurred during the initial rise of HBV DNA with relatively low or normal level of alanine aminotransferase (ALT) in two patients, during the rise of ALT with declining level of HBV DNA in one patient, and during the cholestatic phase of the acute exacerbation in one patient. The acute pancreatitis was clinically silent and only diagnosed by computerized tomography in the remaining patient. Direct viral damage and/or immunological attack to the pancreatic tissue were probably the underlying pathogenesis of the acute pancreatitis in these patients. In conclusion, acute pancreatitis complicating acute exacerbation of chronic HBV infection carried an extremely poor prognosis with high mortality.

Acute Disease↗