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Biomedical subjects

J Ng

Publications and source records attributed to J Ng.

At least 19 recordsLinked to original sources
PubMed2007

HLA-A, -B, -C, -DRB1 allele and haplotype frequencies in an African American population.

Sequence-based typing was used to identify human leukocyte antigen (HLA)-A, -B, -C, and -DRB1 alleles from 564 consecutively recruited African American volunteers for an unrelated hematopoietic stem cell registry. The number of known alleles identified at each locus was 42 for HLA-A, HLA-B 67, HLA-C 33, and HLA-DRB1 44. Six novel alleles (A*260104, A*7411, Cw*0813, Cw*1608, Cw*1704, and DRB1*130502) not observed in the initial sequence-specific oligonucleotide probe testing were characterized. The action of balancing selection, shaping more 'even' than expected allele frequency distributions, was inferred for all four loci and significantly so for the HLA-A and DRB1 loci. Two-, three-, and four-locus haplotypes were estimated using the expectation maximization algorithm. Comparisons with other populations from Africa and Europe suggest that the degree of European admixture in the African American population described here is lower than that in other African American populations previously reported, although HLA-A:B haplotype frequencies similar to those in previous studies of African American individuals were also noted.

Black or African American↗
PubMed2006

Superior ex vivo cord blood expansion following co-culture with bone marrow-derived mesenchymal stem cells.

One factor limiting the therapeutic efficacy of cord blood (CB) hematopoietic progenitor cell (HPC) transplantation is the low cell dose of the graft. This is associated with an increased incidence of delayed or failed engraftment. Cell dose can be increased and the efficacy of CB transplantation potentially improved, by ex vivo CB expansion before transplantation. Two ex vivo CB expansion techniques were compared: (1) CD133+ selection followed by ex vivo liquid culture and (2) co-culture of unmanipulated CB with bone-marrow-derived mesenchymal stem cells (MSCs). Ex vivo culture was performed in medium supplemented with granulocyte colony-stimulating factor, stem cell factor and either thrombopoietin or megakaryocyte growth and differentiation factor. Expansion was followed by measuring total nucleated cell (TNC), CD133+ and CD34+ cell, colony-forming unit and cobblestone area-forming cell output. When compared to liquid culture, CB-MSC co-culture (i) required less cell manipulation resulting in less initial HPC loss and (ii) markedly improved TNC and HPC output. CB-MSC co-culture therefore holds promise for improving engraftment kinetics in CB transplant recipients.

AC133 Antigen↗
PubMed2006

A novel triple purge strategy for eliminating chronic myelogenous leukemia (CML) cells from autografts.

Imatinib-refractory chronic myelogenous leukemia (CML) patients can experience long-term disease-free survival with myeloablative therapy and allogeneic hematopoietic cell transplantation; however, associated complications carry a significant risk of mortality. Transplantation of autologous hematopoietic cells has a reduced risk of complications, but residual tumor cells in the autograft may contribute to relapse. Development of methods for purging tumor cells that do not compromise the engraftment potential of the normal hematopoietic cells in the autograft has been a long-standing goal. Since primitive CML cells differentiate more rapidly in vitro than their normal counterparts and are also preferentially killed by mafosfamide and imatinib, we examined the purging effectiveness on CD34(+) CML cells using a strategy that combines a brief exposure to imatinib (0.5-1.0 microM for 72 h) and then mafosfamide (30-90 microg/ml for 30 min) followed by 2 weeks in culture with cytokines (100 ng/ml each of stem cell factor, granulocyte colony-stimulating factor and thrombopoietin). Treatment with 1.0 microM imatinib, 60 microg/ml mafosfamide and 14 days of culture with cytokines eliminated BCR-ABL(+) cells from chronic phase CML patient aphereses, while preserving normal progenitors. This novel purging strategy may offer a new approach to improving the effectiveness of autologous transplantation in imatinib-refractory CML patients.

Antigens, CD↗
PubMed2006

Diagnostic difficulties in the management of H-type tracheoesophageal fistula.

PURPOSE: To evaluate the diagnostic difficulties and pitfalls in establishing the diagnosis of congenital H-type tracheoesophageal fistula. MATERIAL AND METHODS: A retrospective review of all cases of H-type tracheoesophageal fistula that were diagnosed in a single unit over a 6-year period. The variables assessed were age at presentation, presenting symptoms, time to diagnosis, investigations, and time to surgical repair of H-type fistula. The investigations leading to a definitive diagnosis are assessed and discussed. RESULTS: Between 1998 and 2004, five cases of H-type tracheoesophageal fistula presented to our unit. All cases had an upper gastrointestinal contrast study/tube esophagogram. In addition, four cases had a chest radiograph, three cases had a bronchoscopy, and one case an esophagoscopy. The median delay from the time of first presentation to diagnosis of H-type tracheoesophageal fistula was 14 days (7-58 days). Median age at surgery was 15 days (8-60 days). CONCLUSION: Although symptoms are usually present from birth, the diagnosis of H-type fistula is difficult and often delayed. The various diagnostic techniques are not entirely reliable and fistula identification can be elusive. The authors present recommendations for the diagnostic work-up, which may increase the diagnostic potential and avoid unnecessary delays in the diagnosis and management of H fistula.

Age Factors↗
PubMed2006

Strategies for evaluating B*18 allelic diversity by sequence-based typing applied to studies of a population from Singapore and African-Americans.

Strategies to resolve B*18 alleles which carry a deletion in intron 1 close to the 5' end of exon 2 relative to other HLA-B alleles or a null allele mutation in exon 1 and to resolve ambiguities among allele combinations including B*18 are described. B*18 allele frequencies from volunteer donors recruited for two hematopoietic stem cell registries show the presence of two alleles, B*180101 and B*1802, in a population from Singapore and only B*180101 in African-Americans.

Black or African American↗
PubMed2006

Twenty-three novel HLA-B alleles identified during intermediate-resolution testing.

Twenty-three novel human leukocyte antigen-B alleles are described: B*070204, *0738, *0742, *0821, *130202, *1312, *1575, *1598, *1599, *270507, *2728, *350104, *3558, *3811, *3931, *3932, *4045, *4107, *420501, *4812, *510106, *5520, and *5616. Thirteen of the variants are single-nucleotide substitutions from their most homologous allele, eight resulting in amino acid changes (B*0742, *1312, *1598, *1599, *3558, *3931, *4107, and *5616) and five with silent substitutions (B*070204, *130202, *270507, *350104, and *510106). Three alleles (B*0738, *4812, and *5520) differ by five nucleotide changes, altering four amino acids. The remaining seven alleles differ from their most similar alleles by two to three nucleotides, altering from one to two amino acids.

Alleles↗
PubMed2006

Searching for HLA-DRB1*1206 in volunteer marrow donors in four US population groups.

The frequencies of DRB1*12 alleles were determined in four US population groups by DNA sequencing. Only DRB1*120101 (or DRB1*1206 or *1210) and DRB1*120201 alleles were identified, the latter primarily in the Asian American population. Additional testing of a subset of samples to detect the presence of DRB1*1206 found all of the alleles to be DRB1*120101 (or DRB1*1210). Retesting of six samples previously typed as DRB1*1206 found only DRB1*120101 (or DRB1*1210).

Black or African American↗
PubMed2006

Identification of nine new HLA class I alleles in volunteers from the Singapore stem cell donor registries.

Based on unusual probe hybridization patterns, two human leukocyte antigen (HLA)-A, five HLA-B, and two HLA-C alleles (A*240208, A*3211Q; B*1822, B*3938Q, B*4606, B*4607N, B*5139; Cw*0321, Cw*0734) were identified in individuals from the Singapore Bone Marrow Donor Program and Singapore Cord Blood Bank. Eight of the nine alleles encode amino acid substitutions altering the antigen-binding region including three alleles with changes altering a cysteine at codon 164 (A*3211Q, B*3938Q, B*4607N). This substitution either eliminates a key disulfide bond or results in a stop codon, both likely affecting the expression of the HLA molecules. Only one allele (A*240208) carries a synonymous substitution.

Alleles↗
PubMed2005

Treatment of pulmonary hypertension in the general adult intensive care unit: a role for oral sildenafil?

Use of inhaled nitric oxide for treatment of pulmonary hypertension in adult critical illness is limited by its mode of delivery and high costs, prompting evaluation of alternative therapies. We report the use of oral sildenafil in a patient with severe secondary pulmonary hypertension and right ventricular dysfunction. Following reduction in mean pulmonary artery pressure and pulmonary vascular resistance with inhaled nitric oxide, crossover to sildenafil therapy maintained control of pulmonary hypertension, facilitating discontinuation of respiratory and cardiovascular organ support. The relative pulmonary vascular specificity of oral sildenafil, and its low cost, makes it an attractive therapeutic alternative to inhaled nitric oxide, and warrants further study.

Administration, Oral↗
PubMed2005

Ex vivo expansion of umbilical cord blood.

The efficacy of cord blood (CB) transplantation is limited by the low cell dose available. Low cell doses at transplant are correlated with delayed engraftment, prolonged neutropenia and thrombocytopenia and elevated risk of graft failure. To potentially improve the efficacy of CB transplantation, approaches have been taken to increase the cell dose available. One approach is the transplantation of multiple cord units, another the use of ex vivo expansion. Evidence for a functional and phenotypic heterogeneity exists within the HSC population and one concern associated with ex vivo expansion is that the expansion of lower 'quality' hematopoietic progenitor cells (HPC) occurs at the expense of higher 'quality' HPC, thereby impacting the reserve of the graft. There is evidence that this is a valid concern while other evidence suggests that higher quality HPC are preserved and not exhausted. Currently, ex vivo expansion processes include: (1) liquid expansion: CD34+ or CD133+ cells are selected and cultured in medium containing factors targeting the proliferation and self-renewal of primitive hematopoietic progenitors; (2) co-culture expansion: unmanipulated CB cells are cultured with stromal components of the hematopoietic microenvironment, specifically mesenchymal stem cells (MSC), in medium containing growth factors; and (3) continuous perfusion: CB HPC are cultured with growth factors in 'bioreactors' rather than in static cultures. These approaches are discussed. Ultimately, the goal of ex vivo expansion is to increase the available dose of the CB cells responsible for successful engraftment, thereby reducing the time to engraftment and reducing the risk of graft failure.

Cell Culture Techniques↗
PubMed2005

Ten novel HLA-DRB1 alleles and one novel DRB3 allele.

Ten novel HLA-DRB1 and one DRB3 alleles are described. Eight of the variants are single-nucleotide substitutions, four resulting in an amino acid change (DRB1*1145, *1148, *0828 and *1514) and four with silent substitutions (DRB1*040504, *130103, *160502 and DRB3*020204). Two alleles differ by two nucleotide changes altering one (DRB1*1447 and *1361) amino acid and one allele alters three nucleotides and two amino acids.

Amino Acid Substitution↗
PubMed2005

The time course of visual field recovery following transphenoidal surgery for pituitary adenomas: predictive factors for a good outcome.

OBJECTIVE: To report the quantitative assessment of visual fields (VF) in patients with pituitary macroadenomas, and the time course and predictive factors for recovery of vision. METHODS: Retrospective study of 41 patients with pituitary adenomas and visual disturbance. Patients underwent pre- and postoperative VF assessment at one week, three to six months, one year, two years, and five years using the Humphrey field analyser, which gives a quantitative measure of VF in each quadrant. RESULTS: 36/41 patients (88%) presented with a visual disturbance. Mean (SEM) duration of symptoms was 94 (50) weeks (range 0.5 to 1500); 12 (29%) had optic atrophy at presentation. Impairment of VF was greatest in the upper temporal quadrant, followed by the lower temporal. VF recovery was progressive and apparent even at the five year follow up (p<0.001). Overall, VF returned to normal in 35% of eyes, improved in 60%, and remained unchanged in 5%. Patients whose VF returned to normal had a shorter duration of symptoms (16 (5) v 137 (56) weeks; p<0.05), better preoperative visual acuity (p<0.05), and a smaller degree of impairment in preoperative lateral quadrant VF (p<0.01) than those whose VF only improved. On multivariate analysis, the only predictive factor for VF recovery was the degree of impairment in VF preoperatively. CONCLUSIONS: Transphenoidal surgery for pituitary macroadenoma results in a progressive recovery of VF in 95% of patients. The extent of the VF recovery is mainly dependent on the preoperative VF deficit, which emphasises the need for early intervention in these patients.

Adenoma↗
PubMed2005

Chest radiograph screening for tuberculosis in a Hong Kong prison.

SETTING: Long-stay prisoners are not regularly screened for TB in Hong Kong. OBJECTIVE: To evaluate tuberculosis (TB) screening in prison. METHOD: All prisoners in a maximum security prison as of 31 October 2001 were screened by chest radiograph (CXR), except for those being followed up for TB or examined by CXR in the last 6 months. RESULTS: A total of 814 male prisoners aged 34.6 +/- 9.6 (mean +/- SD) years were successfully screened. Of 53 cases (6.51%) with radiographic abnormalities, 10 active TB cases (8 culture-negative, 2 culture-positive) were diagnosed, giving an overall yield of 1.23% (95%CI 0.59-2.26). There was no statistical difference in age, ethnicity, place of birth or residency status between those with and those without TB (all P > 0.05). Incarceration > or = 2 years, being in current prison > or = 2 years and not having CXR in last 2 years were associated with TB in univariate analysis (all P < 0.05), but only the last remained an independent predictor in multiple logistic regression (OR 16.8, 95%CI 2.1-132.9, P = 0.008). In that group, the yield was 3.1% (95%CI 1.42-5.89). No further cases were detected in the subsequent 2 years. CONCLUSION: CXR screening of long-stay prisoners gave a high yield in this study.

Adult↗
PubMed2003

Limited diversity of HLA-DRB1*02 alleles and DRB1-DRB5 haplotype associations in four United States population groups.

At least 60 DRB1*02 positive individuals from each of four US population groups found within a hematopoietic stem cell volunteer donor registry - Caucasoids, African Americans, Asians/Pacific Islanders, and Hispanics - were randomly selected from a database of 82,979 individuals. DRB1*02 alleles were identified by DNA sequencing. A total of five of 23 known DRB1*02 alleles were detected. DRB1*15011 was the predominant DRB1*02 allele in Caucasoids and Hispanics. The most common DRB1*02 allele observed in African Americans was DRB1*1503, and DRB1*15021 in Asians/Pacific Islanders. Caucasoids were found to be the least diversified; only DRB1*15011 and DRB1*16011 were observed. A subset of individuals was also typed for DRB5 alleles by DNA sequencing. DRB5*01011, DRB5*0102, DRB5*0103, DRB5*0108N and DRB5*0202 were detected and nine DRB1-DRB5 haplotypes defined.

Black or African American↗