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Biomedical subjects

T K Chan

Publications and source records attributed to T K Chan.

At least 73 records · Page 4Linked to original sources
PubMed1995

Further characterization of [3H]U69593 binding sites in the rat heart.

K binding sites in the crude membrane preparation of the rat heart homogenate were further characterized by a displacement binding assay of [3H]-U69593 with specific kappa ligands and a direct binding assay with [3H]-etorphine. Scatchard analysis of specific [3H]-U69593 binding showed that the Kd and Bmax were 6.4 +/- 1.0 nM and 97 +/- 8 fmol/mg protein. respectively. The binding of [3H]-U69593 was effectively displaced by the selective kappa 1 ligands, U-69593 and U-50488H, but only weakly displaced by Met5-enkephalin-Arg6-Phe7, a selective kappa 2 ligand, which showed only 11 +/- 3% inhibition of [3H]-U69593 binding at the concentration of 1 microM. In addition, there was no binding site for [3H]-etorphine, known to bind to mu, delta and kappa 2 binding sites, but not kappa 1 binding sites. The findings suggest that the kappa binding sites in the rat heart most likely belong to the kappa 1 subtype. The binding sites have high and low affinity components as nonlinear regression analysis of the competition curves is best fit by two components with IC50 values of 11 +/- 2 and 62 +/- 7 nM for U-69593, and 9.9 +/- 1.5 and 414 +/- 108 nM for U-50488H. Furthermore, the binding of [3H]-U69593 were inhibited by both monovalent cations (Na+, Li+) and divalent cations (Mg2+, Mn2+ and Ca2+).

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1995

Large granular lymphocyte leukemia. A study of nine cases in a Chinese population.

Large granular lymphocyte (LGL) leukemia is a neoplastic disorder of lymphocytes that is characterized by the presence of prominent cytoplasmic granules, and involves the proliferation of at least two distinct cell types, T cells and natural killer (NK) cells. The authors report the clinical and pathologic features of 9 Chinese patients with LGL leukemia, who represented 14% of 64 cases of chronic lymphoproliferative disorders diagnosed at their centers in 3 years. Three different groups could be defined on immunophenotypic and clinical grounds. The first group of 4 cases were CD2+CD3+CD4-CD8+. With the exception of a pediatric case, these cases ran an indolent course that was similar to the T-cell LGL leukemia most common in Western patients. However, thrombocytopenia and pure red cell aplasia were more common in the patients in this study, which was similar to the experience in Japanese patients. The second group of two cases were CD2+CD3+CD4+CD8-, and appeared to have worse outcomes than the first group. The third group of 3 cases were CD2+CD3-CD4-CD8-CD56+. Although phenotypically similar to the NK-cell LGL leukemia reported in Western patients, these cases were clinically more aggressive than their Western counterparts. This study is the first to report comprehensively the different types of LGL leukemias in Chinese patients, and provides useful information on the similarities and similarities and differences of these disorders as compared to those cases in the West.

Adult↗
PubMed1995

Intensive consolidation chemotherapy for newly diagnosed acute myeloid leukemia using a regime containing moderate dose cytosine arabinoside and mitoxantrone.

Fifty patients with previously untreated acute myeloid leukemia were treated with an induction regimen consisting of cytosine arabinoside 100 mg/m2 per day by 18 h i.v. infusion for 7 days, daunorubicin 50 mg/m2 per day by i.v. bolus injection for 3 days and etoposide 75 mg/m2 per day by 1 h i.v. infusion for 7 days. Thirty seven of them (74%) went into complete remission (CR) and they all then received two consecutive courses of consolidation chemotherapy consisting of cytosine arabinoside 500 mg/m2 per day by 1 h i.v. infusion every 12 h for 4 days (total eight doses) and mitoxantrone 12 mg/m2 daily by 30 min i.v. infusion for 3 days. They were followed by maintenance chemotherapy with cytosine arabinoside and thioguanine 2 monthly. With a median follow up time of 24 months, 20 of the 37 complete responders had relapsed (54%). The disease-free survival (DFS) of 37 CR patients and the overall survival of all patients at 24 months were 37 and 44%, respectively. Age of patients and number of courses of induction chemotherapy to achieve CR were significant factors predicting DFS. Myelosuppression was the major toxic side effects. Ten patients had prolonged marrow suppression following consolidation chemotherapy. In conclusion, despite the significant myelosuppression observed, overall improvement in treatment outcome was not demonstrable with the use of this intensive consolidation therapy.

Adolescent↗
PubMed1995

Trisomy 8 in acute promyelocytic leukaemia: an interphase study by fluorescence in situ hybridization.

Acute promyelocytic leukaemia (APL) is characterized by t(15;17)(q24;q21). Trisomy 8 is the commonest accompanying karyotypic aberration. We investigated 14 APL patients for trisomy 8 using fluorescence in situ hybridization (FISH). Conventional cytogenetic analysis showed trisomy 8 in two of nine successfully karyotyped cases. With FISH, a possible third case showing a subclone (1-2.5%) with trisomy 8 was found. The trisomy 8 clone size defined by karyotyping and FISH was concordant in one case and discordant in another, in which trisomy 8 was found in 100% of metaphases but only in 48% of leukaemic promyelocytes by FISH. Therefore trisomy 8 was mosaic in all the cases, suggesting that it had arisen from clonal evolution. All-trans-retinoic acid successfully induced morphologic remission in both cases with trisomy 8.

Adult↗
PubMed1995

Monitoring of leukocyte cytomegalovirus DNA in bone marrow transplant recipients by nested PCR.

A nested PCR assay for the detection of human cytomegalovirus (CMV) DNA was evaluated by weekly monitoring of blood samples taken from 101 bone marrow transplant (BMT) recipients. When peripheral blood leukocytes were used as the source of CMV DNA, even a modified assay with stringent temperature-cycling conditions was as sensitive as the standard assay. The sensitivity, specificity, and positive predictive value of two consecutively positive leukocytic PCR results with this modified assay in predicting CMV disease of 101 patients submitting 1,441 peripheral blood leukocyte samples were found to be 92.1, 63.5, and 60.3%, respectively. The positive predictive value of patients' seropositivity for CMV was 40%, while that of viremia was 72%. However, viremia followed CMV disease by a median of 1.5 days, while the first leukocytic positive PCR assay preceded disease by a median of 14 days. By use of the criteria of two consecutively positive PCR results instead of recipient CMV seropositivity for starting preemptive ganciclovir treatment, 38 of the 43 recipients with isolated single positive or negative assays (groups I and II) would be spared unnecessary ganciclovir treatment. Moreover, two other findings support the use of antiviral prophylaxis before engraftment in high-risk cases and subsequent preemptive treatment of patients with two consecutively positive PCR assays. First, for 7.9% of 76 patients with positive assays (groups II and III), the first positive PCR assay occurred before engraftment, which implied the presence of viral DNA in the blood (DNAemia) soon after transplantation. Second, isolated single positive assays which were clustered around the second to sixth weeks after transplantation were found for 18 patients (group II) and could represent abortive episodes of CMV infection.

Adolescent↗
PubMed1995

DNA analysis of Huntington's disease in southern Chinese.

Allelic frequencies of RFLPs at loci closely linked to the HD gene, D4S95, D4S91, D4S141, and D4S90, were determined in 13 Huntington's disease (HD) patients from nine Chinese families and 129 normal subjects. These were similar for non-HD and HD chromosomes and the HD gene in Chinese is associated with multiple haplotypes. Hence the HD gene probably arose independently in the background haplotypes of the Chinese population. The heterozygosity rates for the two most useful RFLP sites are 0.659 for D4S95-AccI VNTR and 0.494 for D4S141-HindIII. (CAG)n repeat numbers ranged from 12 to 27 in 174 normal chromosomes. In 52 meiotic recombinations, the (CAG)n repeats were stably inherited in normal families. In HD families, 12 of 13 HD patients had expanded (CAG)n repeats of 40 to 58. Additionally, 10 asymptomatic family members had expanded (CAG)n repeats and the inheritance of the expanded repeat was unstable in these families.

Alleles↗
PubMed1995

Pulmonary infections in bone marrow transplantation: the Hong Kong experience.

The pattern of pulmonary infections in 59 consecutive bone marrow transplantations in Hong Kong was reviewed. Compared with published data from other marrow transplant units, we had a lower incidence of cytomegalovirus pneumonitis (1.7%) and a higher incidence of mycobacterial infections (5%). The latter is probably related to the high background prevalence of tuberculosis in the local population. Treatment with antituberculous drugs was effective.

Bacterial Infections↗
PubMed1995

Treatment outcome and prognostic factors for primary nasal lymphoma.

PURPOSE: To report our experience managing a large series of Chinese patients with primary nasal lymphoma. PATIENTS AND METHODS: From January 1975 to December 1993, 100 patients (median age, 50 years) with newly diagnosed primary nasal lymphoma were studied. There were four low-grade, 62 intermediate-grade, nine high-grade, and 25 unclassifiable lymphomas. Immunophenotyping was performed in 45 patients: eight B cell, 35 T cell, and two uncertain. All cases of angiocentric lymphoma that were typed were T cell. Fifty-two patients had stage I disease, 15 had stage II, four had stage III, and 29 had stage IV. Only 15 patients had B symptoms (weight loss, night sweats, and/or fever), and 11 had bulky disease. Thirty-nine patients with clinically localized stage I and II disease received local radiotherapy alone (before 1980), and the remaining 28 stage I and II patients received combination chemotherapy followed by local radiotherapy. The 33 patients with advanced stage III and IV disease were given combination chemotherapy, and additional radiotherapy was given to five of them who had bulky local disease. RESULTS: Significantly higher complete remission rates were observed in patients with early stages of disease and those without B symptoms. Superior disease-free survival after complete remission was observed in patients with stage I/II disease. Univariate factors associated with a better overall survival included age less than 60 years, stage I disease, and absence of B symptoms. Survival was significantly better in the subgroup of patients with stage I disease. CONCLUSION: Patients with nasal lymphoma, especially those with advanced disease, seemed to have a poor prognosis, and their clinical outcome was not improved significantly by the use of chemotherapy instead of radiotherapy or the use of doxorubicin-containing chemotherapeutic regimens.

Adolescent↗
PubMed1995

Mixed chimerism following bone marrow transplantation for severe combined immunodeficiency: a study by DNA fingerprinting and simultaneous immunophenotyping and fluorescence in situ hybridisation.

We report a girl with severe combined immunodeficiency (SCID) who had a paternal T-depleted bone marrow transplant (BMT) when 11 months old. Engraftment was documented but karyotyping of marrow cells 1 year after BMT showed recipient metaphases (XX) only. However, she remained clinically well and further analysis y karyotyping of PHA-cultured peripheral blood mononuclear cells (PBMC) showed donor metaphases (XY) only. DNA fingerprinting confirmed mixed chimerism in the peripheral blood. The granulocytes were of recipient origin and the PBMC of mixed origin, the donor proportion of which increased after culture with PHA. Using simultaneous immunophenotyping and fluorescence in situ hybridisation (FISH) with chromosomes X and Y-specific probes, circulating T cells were demonstrated to be of donor origin whereas B cells and myeloid cells were mostly of recipient origin.

Adult↗
PubMed1995

Incidence of graft-versus-host disease in Hong Kong Chinese and its influence on survival after bone marrow transplantation from HLA-identical siblings.

Graft-versus-host disease (GVHD) is an important complication of allogeneic bone marrow transplantation (BMT). To assess its influence on transplant outcome, we studied 90 Chinese patients with hematologic disorders with BMT from HLA-identical siblings. GVHD prophylaxis consisted of a combination of methotrexate (MTX) and cyclosporine A (CsA). The incidence of grade II-IV acute GVHD was 29% (95% CI 19-38%). The incidence of limited and extensive chronic GVHD was 30% (95% CI 20-40%). For patients transplanted for early hematologic malignancy (n = 40), those with GVHD (acute and/or chronic) had lower relapse rate (17% (95% CI 0-36%) vs. 54% (95% CI 26-82%), P = 0.043). They had higher transplant-related mortality (12% (95% CI 0-28%) vs. 6% (95% CI 0-18%), P = 0.715) and event-free survival (EFS) (73% (95% CI 53-93%) vs. 43% (95% CI 17-69%), P = 0.104) that had not reached statistical significance. For patients transplanted for advanced hematologic malignancy (n = 37), those with GVHD also had lower relapse rate (5% (95% CI 0-15%) vs. 72% (95% CI 50-94%), P = 0.002) and higher transplant-related mortality (50% (95% CI 27-73%) vs. 8% (95% CI 0-24%), P = 0.006) than those without any GVHD. They had higher EFS (47% (95% CI 24-70%) vs. 26% (95% CI 5-47%), P = 0.609) that had not reached statistical significance. Therefore, the incidence of acute and chronic GVHD in Chinese was similar to that of their Caucasian counterparts using MTX and CsA for GVHD prophylaxis.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1994

The spectrum of chronic lymphoproliferative disorders in Chinese people. An analysis of 64 cases.

BACKGROUND: Chronic lymphoproliferative disorders are considered rare in Oriental patients and are thought to constitute only 2% of all leukemias in these patients, compared to 20-30% in Western patients. We conducted a retrospective analysis of Chinese patients with chronic lymphoproliferative disorders to define the frequency and spectrum of these disorders. METHODS: A consecutive series of Chinese patients with leukemia and lymphoproliferative disorders seen at two regional hospitals in Hong Kong were analyzed retrospectively. The diagnosis of chronic lymphoproliferative disorders was based on morphologic and immunologic criteria proposed by the French-American-British Cooperative Study Group. RESULTS: Sixty-four Chinese patients with chronic lymphoproliferative disorders were identified, and these patients constituted 19% of a total of 342 cases of leukemia diagnosed in 3 years. Chronic lymphocytic leukemia was the most common form, occurring at a frequency of 12.5% of all leukemias. The clinicopathologic features of these patients were similar to those of Western patients, except that Chinese patients tended to present with more advanced (Rai's Stages III and IV; Binet's Stage C) and bulky (splenomegaly > 9 cm) disease, and expressed lambda light chain about six times more frequently. Other chronic lymphoproliferative disorders identified in this study included prolymphocytic leukemia, mantle zone lymphoma, hairy cell leukemia, splenic lymphoma with villous lymphocytes, large granular lymphocyte leukemia, and Sezary syndrome. The authors did not identify any case of human T-cell lymphotropic virus-I-related lymphoproliferative disorders within the study period. CONCLUSION: In addition to providing the frequencies of various chronic lymphoproliferative disorders in southern Chinese people, this study also showed that these disorders no longer should be considered rare in this population. Inherent biologic differences between lymphoproliferative disorders in Chinese and Western patients also may exist.

Adult↗
PubMed1994

Flow cytometric measurement of glycosylphosphatidyl-inositol-linked surface proteins on blood cells of patients with paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired disorder of hematopoiesis in which affected cells are deficient in glycosylphosphatidyl-inositol (GPI) anchored surface proteins. The authors used flow cytometry to study 10 patients with PNH. They used a comprehensive panel of monoclonal antibodies against all nine currently known GPI-linked surface proteins (CD14, CD16, CD24, CD48, CD55, CD58, CD59, CD67, CD73) on cells of various lineages. Deficient cells were identified in the granulocytic-monocytic and erythroid lineages in all patients. However, the lymphoid lineage was affected in only eight patients. The patterns of deficiency were variable, with deficient cells constituting a part to all of the cells in the lineages tested. Certain proteins, including CD16, CD58, and CD59, appeared to be preferentially expressed, despite severe deficiencies of other GPI-linked proteins. Moreover, a trimodal pattern of expression of CD16, CD48, and CD59 was observed, in which a population of cells with intermediate levels of expression were identified in addition to positive and deficient cells. The authors' findings indicated a great degree of heterogeneity in the patterns and levels of expression of the GPI-linked proteins in the various cell types, as well as a possible heterogeneity in lineage involvement. The different patterns of expression of GPI-linked proteins should be considered when using flow cytometry to diagnose PNH. Finally, the clinical progression in some of the patients suggested a possible link between PNH, aplastic anemia, and myelodysplasia.

Adult↗
PubMed1994

A novel haemophilia B defect due to partial duplication of the factor IX gene.

A patient with mild FIX deficiency was found to have partial duplication of the 3' region of the gene, giving, in addition to the a normal gene, another piece of DNA containing exons 5', 6', 7' and 8' and the intervening sequences. Cloning and sequencing of the junction region revealed that crossover occurred at nt 31927 in the 3' untranslated region of one chromosome/chromatid and nt 10640 in intron 4 of the other. No homology or topoisomerase specific sequences were observed in the crossover region. PCR and sequencing of illegitimate FIX transcripts from the patient's lymphocytes showed at least three different species of mRNAs. Translation of two of these 'novel' mRNAs should result in truncated proteins. Possibilities for the splicing of the mature mRNA are offered to explain the translation of a normal-size FIX protein, which was the only product demonstrated on Western blot analysis.

Base Sequence↗