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Biomedical subjects

R Liang

Publications and source records attributed to R Liang.

At least 199 records · Page 11Linked to original sources

Detection of T-cell receptor delta gene rearrangement in T-cell malignancies by clonal specific polymerase chain reaction and its application to detect minimal residual disease.

A clonal-specific polymerase chain reaction technique to detect T-cell receptor delta gene rearrangement in acute lymphoblastic leukaemia (ALL) and non-Hodgkin's lymphoma (NHL) was evaluated. It was applied to detect minimal residual disease. A sensitive and specific technique to detect minimal residual disease for T-cell malignancies was explored. Southern analysis and polymerase chain reaction (PCR) were used to detect the rearranged V-D-J segment of T-cell receptor delta (TCR delta) gene from malignant cell specimens of patients with leukemia and lymphoma of T-cell lineage. The PCR product was sequenced and from the DNA sequences of the V-D-J region, a 3' anti-sense primer was designed and synthesized for clonal specific PCR (CS-PCR). T-cell receptor delta (TCR-delta) gene rearrangement was studied in 40 cases of acute leukaemia and lymphoma of T-cell lineage at diagnosis. Using Southern analysis, the positive rates were 28 and 32% for the 18 T-lymphoma and 22 T-ALL, respectively. A one stage Polymerase Chain Reaction (PCR) technique was used to detect the rearrangement in Southern positive cases and the PCR positive rates were 80 and 86%, respectively. The PCR technique had a sensitivity of 0.1%. Serial follow-up marrow specimens were available from 4 T-ALL patients following chemotherapy for monitoring of minimal residual disease. Their PCR products were DNA sequenced. A 3' primer was designed for each case for a clonal specific (CS) PCR. The technique had a sensitivity of 0.003%. It was applied to detect minimal residual disease in serial follow-up marrow samples. The first patient had persistent negative CS-PCR results and enjoyed continuous remission for more than 3 years. The second patient with negative one stage PCR but positive CS-PCR results had eventual relapse of leukaemia. The other two patients never achieved a morphological remission. These preliminary results appeared to support the usefulness of these PCR techniques in detecting minimal residual disease and predicting relapses for ALL. However, further clinical correlation in larger populations of patients is necessary.

Base Sequence↗

Aggressive non-Hodgkin's lymphoma: T-cell versus B-cell.

This study is aimed to define the clinical characteristics, treatment of outcome and independent prognostic factors of 144 patients with T- and 357 B-cell non-Hodgkin's lymphomas. Entities with well-defined immunophenotype and clinical characteristics were excluded. Patients with T-cell tumours were younger. T-immunophenotype was associated with more advanced disease and presence of B symptoms. They were also less likely to have bulky disease. Primary nasal lymphomas were usually T-cell while lymphomas arising from the gastrointestinal tract and Waldeyer's ring were mostly B-cell. On univariate analysis, T-immunophenotype was associated with lower CR rate, higher relapse rate and inferior overall survival. On the other hand, multivariate analysis revealed that advanced stage, presence of B symptoms, advanced age, high serum lactate dehydrogenase level and use of non-doxorubicin-containing regimens for induction were associated with poor prognosis. Immunophenotype was not a significant independent prognostic factor.

Antineoplastic Combined Chemotherapy Protocols↗

Pattern of T-cell receptor delta gene rearrangement by Southern blotting and polymerase chain reaction technique in Hong Kong Chinese patients with non-T-cell hematological malignancies.

It has been recognized that clonal T-cell receptor delta (TCR delta) gene rearrangement is present in both T-and B-cell malignancies. The highly sensitive polymerase chain reaction (PCR) technique may be applicable to cases of leukemia and lymphoma of non-T-cell origin for detection of minimal residual disease (MRD). A PCR technique was used in this study to investigate the pattern of clonal TCR delta gene rearrangement in Hong Kong Chinese patients with non-T-cell hematological malignancies. Seventy-three patients with the diagnosis of acute leukemia and non-Hodgkin's lymphoma of non-T-cell origin were included in this study. There were 20 patients with common ALL (cALL), seven precursal B-cell ALL (PreB-ALL), 23 acute myeloid leukemia (AML), and 23 non-Hodgkin's lymphoma of B-lineage (B-NHL). Clonal rearrangement was detectable by Southern analysis using a J delta 1 probe in 41 per cent of ALL of B-lineage but in none of the B-NHL or AML. The samples were also studied further by monoclonal PCR amplification for TCR delta gene rearrangement. Three different sets of primers were employed to detect clonal rearrangement of the TCR delta gene. The V delta 1(D)J delta 1 recombination typically seen in T-cell malignancies were not seen in any of the of the non-T-cell malignancies. The V delta 2 (D) D delta 3 recombination was found exclusively in ALL of B-lineage and was seen in 73 per cent of the Southern positive cases. Although clonal TCR delta gene rearrangement was undetectable by Southern analysis in our AML cases, 26 per cent had a V delta 2(D)J delta 1 recombination found by the PCR technique. Sensitivity of the PCR technique was determined by serial mixing and was up to 5-10 leukemic cells per 10(4) nucleated cells. It was apparent from this study that it was feasible to detect clonal TCR delta gene rearrangement by the PCR technique in a proportion of the cases of non-T-cell hematological malignancies. The PCR technique can be applied to detect residual leukemic cells in marrow of patients in an apparent morphological complete remission. The value of this application requires further clinical evaluation and correlation.

Acute Disease↗

All-trans retinoic acid (ATRA) in the treatment of acute promyelocytic leukemia (APL).

Acute promyelocytic leukemia is characterized by the reciprocal translocation of chromosomes 15 and 17. All-trans retinoic acid (ATRA) efficiently induces differentiation of the abnormal promyelocytes. In this study, we had used ATRA as the primary induction therapy for 17 newly diagnosed patients, and as the salvage therapy for 11 patients who relapsed from or were resistant to chemotherapy. All patients received subsequent consolidation chemotherapy. Complete remission (CR) rate, early death rate (within 28 days of diagnosis) were then compared to an historical control of 50 APL patients treated with combination chemotherapy; and event-free survival of the 17 newly diagnosed patients was compared to the historical control. In the ATRA group, 26 of the 28 patients (93 per cent) attained complete remission. Two of 28 (7 per cent) died within 28 days of ATRA therapy. There was no case of primary resistance to ATRA. Combination chemotherapy was added to ATRA in five patients due to rapidly increasing leucocyte count. There was one case of retinoic acid syndrome which resolved with steroid. When compared to the 50 cases of historical control, there is significant improvement in the overall CR rate (92 per cent versus 59 per cent, p = 0.001) and a significant reduction in the early mortality rate (7 per cent versus 41 per cent, p = 0.001). Moreover, when the survival result of the 17 newly diagnosed patients were compared with the control, there is a significant improvement in the projected EFS at 3 years (64 per cent versus 25 per cent, p = 0.007). In conclusion, ATRA was shown to improve the CR rate, reduce induction mortality and significantly prolong the event-free survival.

Adolescent↗

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↗

Molecular rearrangement of the MLL gene in adult acute myeloid leukemia without cytogenetic evidence of 11q23 aberration.

Translocations involving chromosome band 11q23 are frequently found in infant acute leukemia and involve rearrangement of the MLL gene. In this study, 29 cases of adult acute myeloid leukemia (AML) were analyzed to determine the frequency of MLL gene rearrangement. Of these, 19 cases were karyotyped and none showed cytogenetic evidence of 11q23 aberration. MLL rearrangements were demonstrable in four cases, giving a frequency of 14% (4/29). Only one of the four cases with MLL rearrangement showed features typical of leukemia with 11q23 aberration; other cases were indistinguishable from those without MLL rearrangement. There was no apparent difference in presentation blast count, remission, and survival duration when cases with or without MLL rearrangement were compared. Clinicopathologic features of adult AML with MLL rearrangements may be heterogeneous.

Adult↗

Interleukin 6 modulates interleukin-1-and stress-induced activation of the hypothalamic-pituitary-adrenal axis in male rats.

This study examined the interaction between interleukin 6 (IL-6) and IL-1 and between IL-6 and stress on the activation of the hypothalamic-pituitary-adrenal (HPA) axis. Coadministration of IL-6 (100 ng/rat) with IL-1 (20 or 100 mg/ rat) resulted in synergistic stimulation of the HPA axis, as determined by increased plasma levels of ACTH and corticosterone (CORT) which were greater in rats that received both cytokines than in rats receiving either cytokine alone. Concomitant administration of IL-6 (100 ng/rat) with exposure to a novelty stressor also synergistically stimulated the activation of the HPA axis, as IL-6-treated rats subjected to novelty stress had greater increases in plasma levels of ACTH and CORT than vehicle-treated rats exposed to novelty stress or rats receiving IL-6 alone. However, concomitant administration of IL-6 (100 ng/rat) did not significantly affect restraint stress induced elevation of plasma levels of ACTH and CORT, although IL-6 tended to prolong restraint stress induced elevation of plasma levels of CORT. These findings indicate a modulatory role for IL-6 stimulated HPA axis activity in response to IL-1 or a novelty psychological stressor, but not for restraint stress.

Adrenal Glands↗

Report of a case of primary skeletal muscle lymphoma and review of the literature.

Primary extranodal lymphoma arising from skeletal muscle is rare. We describe a case of primary skeletal muscle lymphoma, diffuse large B-cell type. A review of the literature showed that it mostly involves the extremities, especially the thighs, in the elderly and has an aggressive histology of the B-cell immunophenotype. Different pathogenetic mechanisms for the occurrence of malignant lymphoma in extranodal sites are discussed.

Age Factors↗