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R Liang

Publications and source records attributed to R Liang.

At least 37 records · Page 2Linked to original sources

Incidence and spectrum of non-Hodgkin lymphoma in Chinese migrants to British Columbia.

The incidence and spectrum of non-Hodgkin lymphoma (NHL) differ between the Chinese and Caucasian populations. Using population-based registries, we studied the pattern of NHL in Chinese migrants to British Columbia (BC). The records of all NHL cases of Chinese descent diagnosed between 1980 and 1997 were retrieved. Age-standardized incidences were calculated by 5-year intervals in terms of age and calendar years and the relative rates were compared between the migrant, Hong Kong and BC populations. The histological distribution of NHL was compared with 4500 consecutive NHL cases diagnosed in the two populations. A total of 211 cases of migrant NHL were identified, with an age-standardized incidence rate of 7.11 per 100 000 per year, compared with the Hong Kong and BC rates of 7.91 [standardized incidence ratio (SIR) = 0.86, P = 0.01] and 11.88 (SIR = 0.56, P < 0.01). The standardized rates of follicular lymphoma remained low, but the incidence of gastric and nasal natural killer/T lymphomas in migrants were lower than expected. Genetic factors appeared to be stronger than environmental factors in governing the overall incidence of NHL in Chinese. However, certain subtypes of lymphoma may show decreased rates in migrants because of environmental factors.

Adolescent↗

Methylation profiling in multiple myeloma.

BACKGROUND: We analysed the methylation status of a panel of 10 genes including p15, p16, DAPK, p73, VHL, E-CAD, MGMT, RARbeta, RIZ1, and ER. METHODS: The gene promoter methylation status was studied by methylation-specific polymerase chain reaction (MSP) with primers for methylated (M-MSP) and unmethylated (U-MSP) DNA in the bone marrow of 13 patients with myeloma, and one patient with plasmacytoma. RESULT: None of the 10 genes tested were methylated in eight normal bone marrow samples. For the positive control, the sensitivity of M-MSP ranged from 1 x 10(-2) for E-CAD and MGMT, to 1 x 10(-4) for p73. Of the eight diagnostic myeloma marrow samples, hypermethylation of p15, p16, E-CAD, DAPK and ER occurred in six (75%), four (50%), seven (87.5%), eight (100%), and six (75%) patients. Similarly, of the five samples from patients who progressed from plateau phase, hypermethylation of p15, p16, E-CAD, DAPK, and ER occurred in five (80%), two (40%), five (100%), five (100%), and three (60%). None of the cases had hypermethylation of RIZ1, p73, VHL, RARbeta, and MGMT. At diagnosis, all patients had concurrent hypermethylation of at least three genes, and five (62%) had concurrent methylation of four or more genes. One patient with plasmacytoma had methylation of E-CAD, ER, and DAPK. CONCLUSION: p15, p16, ER, DAPK, and E-CAD (but not RARbeta, p73, VHL, RIZ1, and MGMT) were frequently methylated in MM at both diagnosis and disease progression. Future studies of larger scale are needed to identify the genes responsible for disease progression.

Base Sequence↗

Chloramphenicol succinate, a competitive substrate and inhibitor of succinate dehydrogenase: possible reason for its toxicity.

From our previous study [Eur. J. Clin. Pharmacol. 56 (2000) 405] we hypothesized that chloramphenicol succinate (CAPS) may be a competitive substrate for succinate dehydrogenase (SDH). It may be oxidized by SDH to release chloramphenicol (CAP), which may inhibit SDH by feed back mechanism. The present ex-vivo/in vitro study was aimed to investigate this possibility by using human tissues (bone marrow and liver samples) and animal tissues (rat liver and kidney). The effect of different SDH activators and specific inhibitors was studied on CAPS metabolism by SDH. The metabolites and reduction products were detected by using HPLC. In marrow samples, CAPS was slowly oxidized to form CAP. The formation of CAP (oxidation product) was enhanced by FAD and low malonate and inhibited by high malonate and 3-NPA. Similar results were obtained with mitochondria from human and rat tissues. These studies suggest that CAPS could be a competitive oxidative substrate and the metabolite CAP could be an inhibitor at the reduction site. Therefore, SDH could be a target molecule responsible for CAPS induced toxicity.

Animals↗

Antirecipient helper and cytotoxic T-cell frequencies in bone marrow transplantation.

We assayed helper T-lymphocyte precursor frequencies (HTLPf), interferon (IFN)-gamma-producing cell frequencies (IFN-gammaPf) and CTL precursor frequencies (CTLPf) to see if they could predict the severity of acute graft-versus-host disease (aGVHD) and disease relapse after transplantation. In all, 48 bone marrow transplantation (BMT) patients and their HLA-identical sibling (n=29) or matched unrelated donors (MUD) (n=19) were recruited. HTLPf, IFN-gammaPf and CTLPf were measured using a limiting dilution assay (LDA). Patients were followed prospectively to assess the severity of aGVHD and the status of the primary disease after BMT. High (>5 x 10(-6)) HTLPf, CTLPf and IFN-gammaPf were significantly associated with the occurrence and severity of aGVHD in patients who received transplants from HLA-identical sibling. Among patients receiving BMT from MUD, HTLPf and CTLPf, but not IFN-gammaPf, were associated with aGVHD. Five patients had disease relapse post-BMT and the risk was not significantly associated with HTLPf, CTLPf or IFN-gammaPf. Patients with high (>5 x 10(-6)) HTLPf, IFN-gammaPf or CTLPf before BMT are at higher risk of developing aGVHD after transplantation from both matched sibling donors and MUD. Whether these parameters can predict disease relapse would have to be investigated with a larger cohort of patients.

Adult↗

Nonhematologic malignancies after allogeneic hematopoietic stem cell transplantation: incidence and molecular monitoring.

Survivors of allogeneic hematopoietic stem cell transplantation (HSCT) are at a life-long increased risk of secondary nonhematologic malignancies. In 615 adult Chinese allogeneic HSCT patients, nine developed nonhematologic malignancies. The 5-year cumulative incidence was 6.1%, 4.5 times the background cancer incidence. Early-onset (within first 6 months) and late-onset (>3 years) subtypes were observed. Secondary cancers included hepatocellular carcinoma, oral and esophageal squamous cell tumors and lung adenocarcinoma in a female nonsmoker. The spectrum reflected local cancer epidemiology, which was different from Western populations. The pathogenesis might be related to acceleration of pre-existing cancers (early-onset type), or prolonged immunosuppression (late-onset type). DNA chimerism studies showed that all tumors were recipient-derived. In the plasma, DNA in all cases was apparently donor-derived, although aberrantly methylated p15 was detectable in a patient with a p15-methylated secondary cancer, implying that minute quantities of tumor (and therefore recipient) derived DNA might be present.

Adult↗

Non-myeloablative allogeneic peripheral stem cell transplantation for multiple myeloma.

OBJECTIVE: To present an institution's 2-year experience of non-myeloablative allogeneic stem cell transplantation among Chinese patients. DESIGN: Retrospective study. SETTING: Bone marrow transplantation unit at a university hospital, Hong Kong. PATIENTS: Ten patients with multiple myeloma who received non-myeloablative allogeneic stem cell transplantation between March 2000 and October 2002. INTERVENTION: Fludarabine (90 mg/m(2)) and total body irradiation (300 cGy) were given as conditioning regimens, followed by non-myeloablative allogeneic stem cell transplantation. MAIN OUTCOME MEASURES: Engraftment, regimen-related toxicity, treatment-related mortality (in the first 100 days), incidence of graft-versus-host disease, chimerism, disease response, and survival rate. RESULTS: All 10 patients had active disease before transplantation. The donors were eight human leukocyte antigen-matched siblings, a mismatched sibling, and a matched daughter. Satisfactory engraftment before day 21 was achieved without early treatment-related mortality. Five patients developed full donor chimerism by day 28 and three other patients had 100% donor chimerism by day 100. Acute graft-versus-host disease developed in six patients (five with grade III and one with grade IV disease), and chronic graft-versus-host disease developed in eight patients (four with extensive disease). Complete remission and partial response were achieved in three and four patients, respectively. Three patients did not respond to treatment, and one case of relapse was observed. Only one patient, who had shown a partial response, received donor lymphocyte infusion; seven patients received thalidomide for graft-versus-host disease with or without graft-versus-myeloma effect. All patients were alive after a median follow-up of 1 year. CONCLUSION: Non-myeloablative allogeneic stem cell transplantation for multiple myeloma is effective, has low toxicity, and results in low treatment-related mortality. Studies of more cases with longer follow-up durations are required.

Adult↗

Reduced incidence of acute graft versus host disease (GVHD) of the gut in Chinese carriers of Helicobacter pylori during allogeneic bone marrow transplantation.

Helicobacter pylori ( H. Pylori) infection is associated with gastritis and peptic ulcer, but its relationship with gut graft versus host disease (GVHD) is unknown. We investigated the association between H. Pylori carriage and incidence and severity of mucosal toxicity and GVHD in 128 consecutive matched sibling stem cell transplantation (SCT) recipients. Using a verified enzyme linked immunosorbant assay (ELISA), 43.5% of patients had H. Pylori exposure before SCT. There was absolute concordance between serological and breath test data in 40 prospective cases. There was no increased risk in WHO grade 3 or 4 mucositis in H. Pylori carriers. Significant (grade II or above) overall GVHD was only predicted by preceding mucositis (p<0.001), while gut GVHD was associated with increased age (p=0.001) and mucositis (p=0.022). Despite increased incidence with age, H. Pylori carriage was associated with significantly reduced risk of gut GVHD (p=0.04) but not overall GVHD. The reduced risk of immune-mediated gut inflammation in H. Pylori carriers after SCT may be related to the known reduced incidence of inflammatory bowel disease in chronic H. Pylori carriers.

Acute Disease↗

Superconductivity and field-induced magnetism in Pr2-xCexCuO4 single crystals.

We report muon-spin rotation and relaxation (muSR) measurements on single crystals of the electron-doped high-T(c) superconductor Pr2-xCexCuO4. In a zero external magnetic field, superconductivity is found to coexist with dilute Cu spins that are static on the muSR time scale. In an applied field, we observe a mu(+)-Knight shift that is primarily due to the magnetic moment induced on the Pr ions. Below the superconducting transition temperature T(c), an additional source of local magnetic field appears throughout the volume of the sample. This finding is shown to be consistent with field-induced antiferromagnetic ordering of the Cu spins. Measurements of the temperature dependence of the in-plane magnetic penetration depth lambda(ab) in the vortex state are also presented.

Journal Article↗

Treatment of lymphoma relapses after allogeneic hematopoietic stem cell transplantation with intensive chemotherapy followed by infusion of hematopoietic stem cell from the original donor.

Five lymphoma patients relapsed from allogeneic hematopoietic stem cell transplantation (HSCT). Three patients who received myeloablative conditioning had full donor chimerism at relapse, whereas two who received nonmyeloablative conditioning had partially or completely lost the graft. All received mini-BEAM [carmustine (BCNU), etoposide, cytarabine (AraC), melphalan], followed by infusion of HSC (four peripheral blood, one marrow) from the initial donor. Neutropenia and thrombocytopenia were brief, and full donor chimerism was established in all cases. There were four complete and one partial remissions. Graft-versus-host disease occurred in three cases, all with full donor chimerism at relapse. Two patients died subsequently of disease relapse or progression. Another two patients died from fungal infection, one of whom was still in remission at death. One patient had remained in remission 47 months after treatment. Mini-BEAM/HSC is an effective treatment for lymphoma relapses after allogeneic HSCT, but optimal strategies of remission consolidation and prevention of treatment-related complications are needed to improve outcome.

Adult↗

Poor engraftment after allogeneic bone marrow transplantation: role of chimerism analysis in treatment and outcome.

We analyzed the clinical course and risk factors of 18 patients with poor engraftment after allogeneic bone marrow transplantation (BMT), defined as absolute neutrophil count below 0.1 x 10(9)/l 28 days post-BMT. Significant risks associated with non-engraftment included HLA one antigen mismatch, BMT from matched unrelated donor, and a low dose of colony-forming units-granulocyte-macrophage (<10(4)/kg). Examined by a semiquantitative analysis of polymorphic microsatellite markers, donor DNA chimerism on day 28 was found to be predictive of treatment outcome. Seven patients had detectable donor DNA, varying from 43 to 100%. Five of them responded to granulocyte colony-stimulating factor (G-CSF) and achieved engraftment. Two were given further infusions of peripheral blood hematopoietic stem cells (PBSC) from the same donors, resulting in engraftment in one of them. Eleven patients had no detectable donor DNA, and none responded to G-CSF. Autologous regeneration occurred in six of these patients, four after infusion of backup marrow and two spontaneously. The remaining five patients died despite the administration of PBSC from the same or different donors. Regular monitoring of donor DNA chimerism is useful in the management of patients at high risk of poor engraftment.

Adolescent↗

Emergency living related liver transplantation for fulminant reactivation of hepatitis B virus after unrelated marrow transplantation.

We report a unique case of emergency living related donor orthotopic liver transplantation (OLT) for late fulminant reactivation of hepatitis B virus (HBV) after matched unrelated bone marrow transplantation (BMT) for chronic myeloid leukemia (CML). Cessation of lamivudine after BMT for HBV positive patients may carry risks of late fatal HBV reactivation. Similar to fulminant HBV reactivation in the general population, OLT under resumption of lamivudine can be life saving. In our case, concomitantly molecular relapse of CML at the time of liver failure was also cleared by OLT, possibly via a 'liver-graft vs. leukemia' effect. Liver rejection (graft vs. graft disease) was mild due to inherent immunocompromise of the marrow graft. Hence BMT recipients in stable remission should not be denied the opportunity for life-saving solid organ transplantation. A choice of marrow and liver donors with innate HBV immunity may be needed to give the additional advantage of long-term HBV clearance.

Adult↗

Nontuberculous mycobacterial infections in Chinese hematopoietic stem cell transplantation recipients.

Between 1995 and 2002, nine cases of nontuberculous mycobacterium (NTM) were isolated from 462 allogeneic stem cell transplant (SCT) recipients (1.9%), and none from 139 autologous cases. They included three cases each of Mycobacterium fortuitum and M. chelonae, and single cases of M. scrofalaceum, M. gordonnae and M. avium complex. Seven cases were respiratory, including five cases requiring treatment, and two involved infected catheters and vascular conduits. Compared with nine cases of mycobacterium tuberculosis (MTB) isolated in the same period, NTM isolation occurred later after HSCT and involved more unrelated donors. Important risk factors for NTM infection included significant aGVHD (P=0.043), leukemia relapse (P=0.022), MUD and mismatch SCT (P<0.001) and existence of BO (P<0.001). Coinfection with aspergillus was common. Invasive NTM disease required prolonged antimicrobial treatment in five cases due to M. fortuitum and M. chelonae. With better MTB prophylaxis, intensive immunosuppression and better awareness, NTM has become an emerging threat in oriental allogeneic HSCT recipients. The cutoff between colonization and infection, and the threshold for starting treatment is unclear. NTM isolation is a marker for severe immunosuppression and poor prognosis. When there is doubt over species identity or extent of infection, broad-spectrum cover may be prudent.

Adult↗