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M H Ng

Publications and source records attributed to M H Ng.

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

Outcomes and prognostic factors of Chinese children with acute lymphoblastic leukemia in Hong Kong: preliminary results.

BACKGROUND: The Chinese population is the biggest ethnic group in the world. However, there are few reports on the treatment outcome of childhood acute lymphoblastic leukaemia (ALL) among the Chinese population. PROCEDURE: Sixty-five children with ALL were treated with a modified protocol of the Medical Research Council United Kingdom Acute Lymphoblastic Leukaemia protocol X(MRC UKALL X) at the Prince of Wales Hospital, Hong Kong. Most patients were ethnic Chinese. They were divided into groups A and B, depending on whether their presenting leucocyte count being was less or greater than 50 x 10(9)/l, respectively. Group A patients of received induction, early intensification (week 5), cranial irradiation, and maintenance for 3 years. Group B patients received an additional late intensification (week 20). RESULTS: The median follow-up duration was 6.8 years(range: 3.4-10.1 years). The event-free and overall survival rates of all patients at 7 years were 66% (confidence interval [CI] 53-76) and 75% (CI 63-84), respectively. The event-free survival rates of groups A and B at 7 years were 67% (CI 52-79) and 60% (CI 32-80), respectively (P= 0.39). The overall survival rates of groups A and B at 7 years were 80% (CI 66-89) and 60% (CI 32-80), respectively (P = 0.07). With this treatment protocol, the factors which adversely affected the outcome were age (<2 years and >10 years) and T-cell subtype. Sex, white blood count at diagnosis, and FAB subtypes were not statistically significant prognostic factors. CONCLUSIONS: The treatment outcomes were comparable with those reported from the MRC UKALL X trials.

Adolescent↗
PubMed1999

Combined morphological and interphase fluorescence in situ hybridization study in multiple myeloma of Chinese patients.

To gain insight into the real incidence of the numeric chromosomal aberrations and the cell lineage involvement of the neoplastic process in multiple myeloma (MM), we examined 18 Chinese MM patients by May-Grunwald-Giemsa (MGG) staining and fluorescence in situ hybridization using three DNA centromeric probes specific for chromosomes 3, 7, and 9. In this investigation, cytogenetic abnormalities were detected in plasma cells (PCs), myeloid cells (MCs), and lymphoid cells (LCs) in all of the MM patients studied. This is the first demonstration of the cytogenetic aberration involved in the myeloid series. Furthermore, the MCs and PCs of 16 MM patients had the same aneuploidies in one or more of the chromosomes analyzed. These data suggest that the neoplastic transformation of MM may occur early in the hematopoietic development. Chromosomal aberrations involving mainly subclones and considerable cellular heterogeneity with gain of a variety of copy numbers of the same chromosome were demonstrated within PCs, which may possibly be the result of an underlying defect of PCs in the control of their number of chromosomes. Whereas PCs showed evidence suggestive of increased polyploidization, MCs and LCs, which exhibited similar chromosomal patterns as the former, rarely did. Thus, the clonal evolution from LC to PC, if that happens in MM, is characterized by chromosomal instability favoring growth of tumor cells with polysomies and polyploidies.

Adult↗
PubMed1999

DNA methylation changes and multiple myeloma.

In contrast to classical mutations, DNA methylation is a mechanism of changing the base sequence without altering the coding function of a gene. The interplay between this epigenetic modification and classical mutations plays an important role in tumorigenesis. Global genomic hypomethylation has been associated with the induction of chromosomal instability, which is commonly seen in solid tumors and multiple myeloma. De novo methylation of CpG islands on the promoter region may contribute to the progressive inactivation of growth-inhibitory genes resulting in the clonal selection of cells with growth advantage. Recently, alteration of p16 and p15 solely by hypermethylation has been detected in high frequencies hitherto unreported in multiple myeloma (MM). Hypermethylation of p16 has been shown to be associated with plasmablastic disease (p=0.026) in primary MM and transcriptional silencing of p16 and p15 has also been found to correlate with hypermethylation of these genes in MM-derived cell lines. Our results in studies with cell lines and primary MM support the fact that hypermethylation of p16 and p15 plays an important role in MM tumorigenesis. Because of its high frequency, the presence of hypermethylation of p16 may prove to be a useful tumor marker for the majority of MM patients. Promoters silenced by methylation can be reactivated by treatment with the demethylating agent 5-aza-2'deoxycytidine. The reversibility of this epigenetic inactivation of the p16 and p15 genes in MM may also provide a broad clinical application in the development of new therapeutic interventions in this uniformly fatal form of cancer.

Carrier Proteins↗
PubMed1998

Epstein-Barr virus expression within keratinizing nasopharyngeal carcinoma.

Three stages of maturation can be seen in keratinizing nasopharyngeal carcinomas. These stages are similar morphologically to basal cells, intermediate and superficial squamous cells seen in normal squamous epithelium. Taking advantage of such a diverse tumour cell population, 10 keratinizing nasopharyngeal carcinoma (NPC) were examined by in situ hybridization for the presence of latent Epstein-Barr Virus (EBV) using EBV encoded RNAs (EBERs) and by immunohistology for the presence of EBV early antigen-diffuse (EA-D) and the 350/220 kd membrane glycoprotein of the EBV. The basal cell-like tumour cells are mainly infected latently with the virus; viral replication was found in isolated intermediate squamous cells, whilst superficial squamous cells are largely depleted of all the viral markers. We used a control series of nonkeratinizing nasopharyngeal carcinomas composed of undifferentiated and poorly differentiated tumour cells and EBV latency was present in these tumours. Viral replication was detected by RT-PCR, in the undifferentiated tumours but viral replication was not seen by immunohistology. The possible relationship between EBV life cycle in these tumours and tumour cell differentiation is discussed in the light of these findings.

Antibodies, Monoclonal↗
PubMed1998

Development and evaluation of an Epstein-Barr virus (EBV) immunoglobulin M enzyme-linked immunosorbent assay based on the 18-kilodalton matrix protein for diagnosis of primary EBV infection.

A new immunoglobulin M (IgM) enzyme-linked immunosorbent assay (ELISA) based on the recombinant Epstein-Barr virus (EBV) matrix protein was developed. Compared to indirect immunofluorescence for the detection of IgM antibody to the EBV capsid antigen on clinical specimens, the sensitivity and specificity of the new IgM ELISA were 96 and 96%, respectively.

Antibodies, Viral↗
PubMed1998

Serological diagnosis of nasopharyngeal carcinoma by enzyme linked immunosorbent assay: optimization, standardization and diagnostic criteria.

OBJECTIVES: To produce an enzyme linked immunosorbent assay (ELISA) to detect antibodies against Epstein Barr virus (EBV) specified nuclear antigen 1 (EBNA 1) and the 18 kD EBV matrix protein, and to determine and optimize its sensitivity and specificity for the diagnosis of nasopharyngeal carcinoma (NPC). METHODS: We used a combination of highly purified glutathione transferase fusion proteins of the 40 kD carboxy domain of EBNA1 and the 18 kD EBV matrix protein for coating ELISA plates. In three separate studies, we tested for IgA antibodies in serum specimens from 28 EBV seronegative donors, 284 EBV seropositive donors and 160 newly diagnosed NPC patients. By comparing the sensitivity and specificity of diagnosis obtained for different cutoff values, we derived several quantitative parameters to evaluate assay performance, establish objective diagnostic criteria which optimize the intrinsic diagnostic capability of the assay and assess the significance of individual test results, respectively. Optimum cutoff optical density (OD) is defined as the cutoff OD where sensitivity of the assay equals its specificity, and resolution of the assay is indicated by the value of sensitivity (or specificity) determined at the optimum cutoff OD. Diagnosis of NPC was achieved by setting a cutoff zone at +/- 20% of this value. RESULTS: All the EBV seronegative donors tested were not reactive, and most of the EBV seropositive donors were weakly reactive, while the majority of NPC patients were moderately or strongly reactive. While the assay was thus shown to be specific for EBV, there was an overlap in the level of these serum antibodies between few individuals of the two latter groups. It was shown that the assay performed equally well in two separate studies conducted under different testing conditions and using different collections of sera in that assay resolution determined on these occasions were 86% and 87% respectively. Diagnosis of NPC can be achieved at the same expected sensitivity of 89% and 83% determined at the lower and upper limits of the cutoff zones, with the corresponding values of specificity being 78% and 91%. It was further shown in the third study that resolution of the assay can be increased to 90% using an assay produced with a higher concentration of the same antigens, and that diagnosis of NPC can be achieved at a higher sensitivity ranging between 86% and 95% at a corresponding specificity of 93% and 86%. CONCLUSIONS: After optimization and standardization, the ELISA can achieve a sensitivity ranging from 86% to 95%, with corresponding specificities of 93% and 86% respectively for the diagnosis of NPC.

Antibodies, Viral↗
PubMed1998

Transcriptional silencing of the p16 gene in human myeloma-derived cell lines by hypermethylation.

Recently, p16 and p15 have been identified as commonly inactivated tumour suppressor genes in haematological malignancies. We previously reported that these genes were frequently hypermethylated in multiple myeloma (MM). To investigate how p16 and p15 inactivation are associated with hypermethylation, methylation status and transcription of these genes in six MM-derived cell lines were studied by Southern blot analysis and RT-PCR. Aberrant methylation of p16 was found in ARH-77, HS-Sultan, IM-9, RPMI-8226, U266-B1 and NCI-H929 MM cell lines. However, loss of p16 transcription was demonstrated only in HS-Sultan, RPMI-8226, U266-B1 and NCI-H929 with extensive methylation at the 5' upstream region of p16. Conversely, only HS-Sultan showed extensive methylation at the 5' upstream region of p15, which was associated with p15 transcriptional block. These results suggest that extensive methylation within a critical domain may be crucial in silencing p16 or p15 transcription. To demonstrate the reversibility of methylation and its relationship with transcription, HS-Sultan, RPMI-8226 and NCI-H929 were demethylated with 5-aza-2'-deoxycytidine. Restoration of gene transcription was observed and correlated with partial demethylation of the genes. The present data show that the p16 and p15 genes are silenced in MM by hypermethylation, which may play an important role in MM pathogenesis.

Blotting, Southern↗
PubMed1997

Frequent hypermethylation of p16 and p15 genes in multiple myeloma.

Both p16 and p15, encoded by the genes located on chromosome 9p21, are inhibitors of cyclin-dependent kinases (CDK4/6) and the upstream regulators of Rb function. In hematopoietic malignancies, deletion of p16/p15 locus has been shown to be highly specific to lymphoid, and more particularly from B-lineage malignancies except multiple myeloma (MM). To investigate whether these genes are inactivated by deletions, mutations, and hypermethylation of the 5' CpG islands, we examined 12 MM patients by Southern hybridization and polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis. No deletions nor mutations of the p16 and p15 genes were found. However, hypermethylation was observed in 75% for p16 and 67% for p15 in our group of MM patients. Such high frequencies of involvement of these genes in MM make them hitherto the most common genetic abnormalities in this disease. Concomitant hypermethylation, uncommon thus far in the literature of the study of these genes, is a rather common phenomenon, occurring in 67% of our patient group. Moreover, hypermethylation of p16/p15 was associated with blastic disease and concomitant hypermethylation of both genes may be pathogenetically related to plasmacytoma development. These results indicate that these genes are important in MM pathogenesis. Here we report, for the first time in the literature, the high incidences of p16 and p15 alterations in MM, not by homozygous deletions or mutations, but solely by hypermethylation of the 5' CpG islands, which may be a specific mechanism in this disease.

Adult↗
PubMed1997

Human herpesvirus-6 and human herpesvirus-7 infections in bone marrow transplant recipients.

Human cytomegalovirus (HCMV), human herpesvirus-6 (HHV-6), and human herpesvirus-7 (HHV-7) DNA in peripheral blood leukocytes (PBL) of 61 bone marrow transplant recipients was monitored weekly during the first 12 weeks post-transplantation by a nested polymerase chain reaction (PCR). Thirty-seven (61%), 17 (28%), and 32 (53%) of patients had one or more PBL specimens positive for HCMV, HHV-6 or HHV-7 DNA, respectively. HHV-7 DNA in PBL during the early post-transplant period was associated with a longer time to neutrophil engraftment (mean 28.8 days vs 19.8 days; P = 0.01). In two patients who failed to engraft, HHV-6 DNA and HHV-7 DNA was detected in plasma and PBL, respectively, early in their post-transplant period. Patients with HCMV disease were more likely to have concurrent HHV-7 DNA in PBL prior to onset of disease than were patients with asymptomatic HCMV infection, suggesting that HHV-7 may be a cofactor in the progression from HCMV infection to HCMV disease. In the 17 patients (179 specimens) in whom viral DNA in plasma was studied (in addition to PBL), a positive result was found only in 3. In each, viral DNA in plasma appeared to correlate with clinically significant disease. HHV-7 DNA in plasma was associated with encephalitis in an allograft recipient.

Acyclovir↗
PubMed1997

Monitoring the therapy of pulmonary tuberculosis by nested polymerase chain reaction assay.

Monthly clinical and microbiological parameters (by sputum smear, culture and PCR assay), of 50 patients with documented pulmonary tuberculosis and on anti-tuberculosis therapy, were monitored over a period of 18 months. PCR converters (70%) who had PCR conversion before the sixth month of treatment did not have clinical or microbiological evidence of failure or relapse, while nine of 15 PCR persisters (30%) had clinical failure (7) and relapse (2). The PCR persisters were significantly associated with more underlying medical illnesses, high mean radiographic scores on the extent of disease involvement, previous drug treatment, initial sputum smear positivity and multi-drug resistance. Of the eight PCR persisters infected by susceptible Mycobacterium tuberculosis, all had marked residual radiographic changes despite completion of drug therapy. The findings may have important implications in the application of PCR on individualization of the duration of anti-tuberculosis therapy.

Adult↗
PubMed1997

Acute myeloid leukemia following psoralen with ultraviolet A therapy: a fluorescence in situ hybridization study.

A woman with mycosis fungoides treated by psoralen with ultraviolet A (PUVA) and electron beam therapy developed acute myeloid leukemia (AML) three years later. Karyotypic analysis of the leukemia cells revealed monosomy 7. Fluorescence in situ hybridization showed that the monosomy 7 clone had accounted for about a third of the marrow cells after PUVA treatment, but replaced the entire marrow at leukemic transformation. These findings were consistent with a secondary AML evolving from an underlying myelodysplasia, supporting that PUVA therapy might have a mutagenic effect on hematopoietic cells. This might be related to its effect on circulating hematopoietic stem cells.

Chromosomes, Human, Pair 7↗
PubMed1997

Nasopharyngeal carcinoma research in Hong Kong in the past decade.

OBJECTIVE: To review the research carried out in Hong Kong on nasopharyngeal carcinoma (NPC) over the past 10 years. METHODS: The literature published in Hong Kong over the past 10 years on nasopharyngeal carcinoma were reviewed in the light of other important international publications on the same subject. RESULTS: The research carried out in Hong Kong covers etiology, natural behavior, treatment and prognosis of NPC. These studies not only elucidated the different aspects of NPC, many of these new findings will also guide future directions of research. CONCLUSIONS: Major efforts have been made to research into the various aspects of NPC with important findings which will translate into better treatment results. As this tumor is uncommon in other parts of the world, continued efforts to improve the prevention, early diagnosis, treatment and care of this tumor are required in China.

Carcinoma in Situ↗
PubMed1996

Detection and serogroup differentiation of Salmonella spp. in food within 30 hours by enrichment-immunoassay with a T6 monoclonal antibody capture enzyme-linked immunosorbent assay.

We previously described an antigen capture enzyme-linked immunosorbent assay which makes use of monoclonal antibody T6, which recognizes an epitope on the outer core polysaccharide of Salmonella lipopolysaccharide molecules that is common to almost all Salmonella serovars. In this paper, we show that this assay can detect between 10(5) and 10(7) Salmonella cells per ml even in the presence of excess Escherichia coli. A total of 153 of 154 (99%) serogroup A to E strains and 51 of 78 (71%) serogroup F to 67 strains were reactive as determined by this assay. This corresponds to a detection rate of approximately 98% of all salmonellae known to affect humans. None of the 65 strains of non-Salmonella bacteria tested positive. Taking advantage of the O-factor polysaccharides also present on the antigen captured by the immobilized T6 antibody, we showed that 136 of 154 Salmonella serogroup A to E strains (88%) were correctly differentiated according to their serogroups by use of enzyme conjugates of a panel of O-factor-specific monoclonal antibodies. We evaluated this assay for the detection and serogroup differentiation of salmonellae directly from enrichment cultures of simulated food, eggs, pork, and infant formula milk. All 26 samples which had been contaminated with Salmonella spp. were detected by T6 (100% sensitivity), with only one false-positive result from 101 samples not contaminated by Salmonella spp. (99% specificity). The detection time was substantially reduced to between 17 and 29 h, depending on the enrichment methods used. Since there were no false-negative results, we concluded that this enrichment-immunoassay method can afford rapid screening for Salmonella spp. in food samples.

Animals↗
PubMed1996

Tissue distribution of Epstein-Barr virus genotypes.

The genome of naturally occurring Epstein-Barr virus contains either two or three copies of a 29-bp tandem repeat sequence in the first intron of the BZLF gene. These genotypes differ markedly in their distribution between blood and epithelial tissues, presumably because they have adapted to separate life cycles in these sites. The genotype prevalent in the blood also appears to be better able to transform B lymphocytes.

Genome, Viral↗
PubMed1996

Single-tube nested PCR in the diagnosis of tuberculosis.

AIMS: To evaluate the usefulness of a single-tube nested polymerase chain reaction (PCR) assay in the diagnosis of tuberculosis in 1497 pulmonary and 536 extrapulmonary specimens. METHODS: A single-tube nested PCR, utilising two sets of primers with different melting temperatures (88 degrees C for external primers; 70 degrees C for internal primers) to augment sensitivity and specificity without increasing the risk of amplicon contamination, was evaluated. Specimens were initially tested for the repetitive IS6110 sequences and if negative, retested for the universal 38 kilodalton sequence and for inhibitors. dUTP/Uracil-N-glycosylase and Instagene treatment were used to minimise contamination and the effect of inhibitors, respectively. RESULTS: Using culture as the gold standard, the overall sensitivity of the assay was 89% for pulmonary and 42% for extrapulmonary specimens. Sensitivity varied greatly with respect to sample type (92% for follow up specimens from a chest hospital and 70% for non-follow up specimens from a general hospital). The smear positivity rates were 15% for extrapulmonary specimens, and 69% and 45%, respectively, for follow up and non-follow up specimens from pulmonary sites. Specificity was 99.7%. Inhibitors were present more frequently in extrapulmonary than in pulmonary specimens (13.4% v 2.7%). CONCLUSION: Despite the high sensitivity of the PCR assay for the diagnosis of tuberculosis in pulmonary specimens, it was less effective in the extrapulmonary samples. This is probably because of the lower bacterial load in extrapulmonary specimens, the presence of more inhibitors adversely affecting the PCR assay and the higher volume of specimens used for culture.

Base Sequence↗
PubMed1996

A more immunosuppressive pre-transplant conditioning may be required for Chinese patients with thalassaemia.

Bone marrow transplantation was performed on 14 Chinese patients with transfusion dependent thalassaemia major (n = 13) and haemoglobin H disease (n = 1). The donors were HLA identical siblings. The source of haematopoietic stem cells were from bone marrow (n = 13) and umbilical cord blood (n = 1). The pre-transplant conditioning regimens were (1) busulphan 14 mg/kg and cyclophosphamide 200 mg/kg in two patients; (2) busulphan 16 mg/kg, cyclophosphamide 200 mg/kg and anti-thymocyte globulin 110 mg/kg in five patients; (3) busulphan 16 mg/kg, cyclophosphamide 150 mg/kg and anti-thymocyte globulin 110 mg/kg in seven patients. Graft-versus-host disease prophylaxis was cyclosporin A and methotrexate. All patients engrafted and achieved stable haematopoiesis except the one who underwent the umbilical cord blood transplant, who had autologous marrow recovery. One patient who had stable engraftment rejected the marrow graft and developed aplastic anaemia 4 months after BMT. This patient had a second BMT but rejection recurred again. She eventually died of septicaemia. The other 12 patients were transfusion independent and disease free. The majority have gone back to school or work. Disease-free and actuarial survival probability were 85 and 93%, respectively with a median follow-up time of 30 months (13 to 42 months). Our data suggest that BMT from HLA identical siblings for transfusion dependent thalassaemia gives a high chance of cure with acceptable mortality and morbidity, and that a more immunosuppressive pre-transplant conditioning schedule may be required to prevent rejection.

Adolescent↗