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Biomedical subjects

G Ng

Publications and source records attributed to G Ng.

At least 19 recordsLinked to original sources
PubMed2006

The Royal College of Paediatrics and Child Health programme for subspecialty training.

The National Grid is a training scheme that represents a unique partnership between Deaneries and the Royal College of Paediatrics and Child Health (RCPCH) in offering through national competition, equitable access to high quality subspecialty training. Paediatrics is unusual in that within the umbrella Certificate of Completion of Specialist Training in paediatrics there is the potential to train in one of 13 recognised paediatric subspecialties.

Attitude of Health Personnel↗
PubMed2001

PCR-RFLP typing detects new HLA-DRB1 alleles: DRB1*13022, DRB1*1336 and DRB1*1435.

It is difficult to resolve all heterozygous combinations of the HLA-DRB1*03, *08, *11, *12, *13 and *14 allele group in a one-step generic HLA-DRB1 typing system. Therefore, it is common to employ a secondary technique utilizing group-specific primers to amplify this group of alleles separately from the other HLA-DRB1, -DRB3, -DRB4 and -DRB5 alleles. This paper describes a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method for broad typing of the HLA-DRB1*03, *08, *11, *12, *13 and *14 alleles which, as well as being time-efficient and cost-effective, has so far allowed the detection of 10 new alleles. The new alleles were identified after following up unusual or novel PCR-RFLP patterns. Of the 10 novel alleles found so far with this method, seven have been described previously while three, DRB1*13022, DRB1*1336 and DRB1*1435, are presented here.

Alleles↗
PubMed2000

HLA and other host factors in transfusion-acquired HIV-1 infection.

The host and viral factors that underlie infection with HIV-1 vary considerably with some individuals progressing to AIDS within 3 to 5 years after infection, whereas others remain clinically asymptomatic for over 10 years. Host factors that may contribute to disease progression include HLA and allelic variants of the chemokine receptors CCR5 and CCR2, which have been shown to influence both long-term survival and rapid progression. In this study, we have examined the contribution of HLA and polymorphisms in CCR5 and CCR2 to long-term survival in transfusion-acquired HIV-1-infected individuals. We have found a higher number of HLA-A32 and -A25 alleles but a lower number of the HLA-B8 allele in the study group compared with the frequencies seen in the HIV-1-negative Australian caucasian population. However, there was no apparent contribution by allelic variants of CCR5 and CCR2 to long-term survival and the combined influence of HLA and CCR polymorphisms could not be evaluated in this relatively small (n = 20) group of study subjects. The results of this work support a role for HLA in long-term nonprogression though the presence in the Sydney Blood bank Cohort of nef-defective HIV-1 may confound associations between certain HLA alleles and long-term survival in the face of infection with HIV-1.

Adult↗
PubMed2000

Routine HLA-B genotyping with PCR-sequence-specific oligonucleotides (PCR-SSO) detects eight new alleles: B*0807, B*0809, B*1551, B*3529, B*3532, B*4025, B*5304 and B*5508.

This paper describes eight new alleles (B*0807, B*0809, B*1551, B*3529, B*3532, B*4025, B*5304 and B*5508) that have been found by routine HLA-B genotyping with sequence-specific oligonucleotides (SSOs). All of the new alleles have variations which cause changes in residues that occur within antigen binding pockets and T-cell recognition sites of the antigen. The new polymorphisms within these new alleles may affect the nature and specificity of peptide binding and cause differential T-cell activation, which may have an affect in transplantation.

Alleles↗
PubMed2000

TAMBIS: transparent access to multiple bioinformatics information sources.

UNLABELLED: TAMBIS (Transparent Access to Multiple Bioinformatics Information Sources) is an application that allows biologists to ask rich and complex questions over a range of bioinformatics resources. It is based on a model of the knowledge of the concepts and their relationships in molecular biology and bioinformatics. AVAILABILITY: TAMBIS is available as an applet from http://img.cs.man.ac.uk/tambis SUPPLEMENTARY: A full manual, tutorial and videos can be found at http://img.cs.man.ac.uk/tambis. CONTACT: tambis@cs.man.ac.uk

Computational Biology↗
PubMed1998

Molecular characterization and expression of cloned human galanin receptors GALR2 and GALR3.

Galanin is a 29- or 30-amino acid peptide with wide-ranging effects on hormone release, feeding behavior, smooth muscle contractility, and somatosensory neuronal function. Three distinct galanin receptor (GALR) subtypes, designated GALR1, 2, and 3, have been cloned from the rat. We report here the cloning of the human GALR2 and GALR3 genes, an initial characterization of their pharmacology with respect to radioligand binding and signal transduction pathways, and a profile of their expression in brain and peripheral tissues. Human GALR2 and GALR3 show, respectively, 92 and 89% amino acid sequence identity with their rat homologues. Radioligand binding studies with 125I-galanin show that recombinant human GALR2 binds with high affinity to human galanin (K(D) = 0.3 nM). Human GALR3 binds galanin with less affinity (IC50 of 12 nM for porcine galanin and 75 nM for human galanin). Human GALR2 was shown to couple to phospholipase C and elevation of intracellular calcium levels as assessed by aequorin luminescence in HEK-293 cells and by Xenopus melanophore pigment aggregation and dispersion assays, in contrast to human GALR1 and human GALR3, which signal predominantly through inhibition of adenylate cyclase. GALR2 mRNA shows a wide distribution in the brain (mammillary nuclei, dentate gyrus, cingulate gyrus, and posterior hypothalamic, supraoptic, and arcuate nuclei), and restricted peripheral tissue distribution with highest mRNA levels detected in human small intestine. In comparison, whereas GALR3 mRNA was expressed in many areas of the rat brain, there was abundant expression in the primary olfactory cortex, olfactory tubercle, the islands of Calleja, the hippocampal CA regions of Ammon's horn, and the dentate gyrus. GALR3 mRNA was highly expressed in human testis and was detectable in adrenal gland and pancreas. The genes for human GALR2 and 3 were localized to chromosomes 17q25 and 22q12.2-13.1, respectively.

Amino Acid Sequence↗
PubMed1996

A novel gene codes for a putative G protein-coupled receptor with an abundant expression in brain.

Following the cloning of the dopamine receptors we continued a search of the human genome for related genes. We searched an EST data base and discovered cDNA fragments encoding novel G protein-coupled receptor genes. The available GenBank sequence of one of these EST fragments showed that it encoded a receptor with closest similarity to the D2 dopamine and adrenergic receptors. This cDNA was used to isolate the gene (GPR19), and the encoded receptor also demonstrated similarity with the neuropeptide Y receptor. The gene was mapped to chromosome 12, in region p13.2-12.3. Northern blot analysis revealed expression of GPR19 in peripheral regions, and brain regions significantly overlapping with the D2 receptor gene expression. A sequence of the rat orthologue of GPR19 was obtained and in situ hybridization analysis demonstrated a very abundant expression in rat brain.

Amino Acid Sequence↗
PubMed1995

Myocardial infarction in young adults: angiographic characterization, risk factors and prognosis (Coronary Artery Surgery Study Registry).

OBJECTIVES: This study examined the angiographic characteristics, coronary risk factors and prognosis in young men and women with a history of myocardial infarction compared with that in older patients. BACKGROUND: There are few data regarding myocardial infarction in young adults. It is undetermined whether the development of myocardial infarction at a young age represents a form of coronary heart disease with an adverse prognosis. METHODS: Of the 8,839 patients with a history of myocardial infarction in the Coronary Artery Surgery Study (CASS), there were 294 men < or = 35 years old and 210 women < or = 45 years old. Coronary anatomy, baseline characteristics and prognosis were compared in younger and older patients. RESULTS: Young men and women more often had angiographically normal coronary arteries, nonobstructive disease < 70% stenosis and single-vessel disease than older patients (p < 0.0001). Current smoking was more frequent in young patients (p < 0.0001). Hypertension and diabetes were more frequent in both older men and women, whereas a positive family history of premature coronary disease was significantly more prevalent only in young men. The survival rate at 7 years was improved for young men compared with that in older men (84% vs. 75%, p = 0.0094) and for young women compared with that in older women (90% vs. 77%, p = 0.0004). When multivariate analysis was applied to the data, the survival advantage for young patients remained after adjustment. CONCLUSIONS: Young patients with a myocardial infarction have a favorable prognosis compared with that in older patients.

Adult↗
PubMed1995

Infiltration of the kidney by alpha beta and gamma delta T cells: effect on progression in IgA nephropathy.

We have studied renal biopsies from three groups of patients to determine if alpha beta T cells or gamma delta T cells are present, and whether their presence is correlated with disease progression in IgA nephropathy (IgAN). Group one comprised thin basement membrane disease biopsies (non-immunological control, N = 7); group two were patients with IgAN and stable renal function one year following biopsy (stable, N = 7); and group three were IgAN patients with rapidly declining renal function after one year (progressive, N = 7). Immunohistochemical staining using monoclonal antibodies (CD3, TcR beta, TcR delta) and molecular studies utilizing polymerase chain reaction amplification of cDNA transcribed from biopsy RNA, with primers specific for either the alpha beta TcR or gamma delta TcR, were undertaken. On immunohistochemistry a significant increase in CD3 + cells in progressive biopsies was seen (vs. control P = 0.002, vs. stable P = 0.002). The progressive biopsies infiltrate consisted of both alpha beta TcR (vs. control P = 0.001, vs. stable P = 0.003) and gamma delta TcR cells (vs. control P = 0.01). The RNA study demonstrated an increase in TcR C alpha transcription in the progressive (vs. control P = 0.003) biopsies. Increased TcR C delta transcription was seen in the progressive group (vs. control P = 0.01, vs. stable P = 0.02). We confirm that the presence of lymphocytes in IgAN biopsies predicts progressive disease. While alpha beta T cells are found in both stable and progressive disease, the presence of gamma delta T cells is only associated with progressive IgAN.

Adult↗
PubMed1992

Cytokinesis is more rapid in Ha-T24-ras transfected rat embryo fibroblasts than in non-transfected control cells.

It has long been known that neoplastic cells are characterized by increases in cell motility. Earlier studies from this laboratory indicated that mitotic events were also altered in many tumor and experimentally transformed cells and that this included increases in metaphase duration and a reduction in the duration of cytokinesis. The studies presented in this paper were done to determine whether or not transfection of normal rat embryo fibroblasts by the Ha-T24-ras oncogene could also produce such alterations in mitotic events. The results obtained with the use of time lapse video microscopy indicate that neither the duration of metaphase nor the rate of chromosome movement during anaphase was altered but that the rate of furrow progression during cytokinesis occurred at a significantly more rapid rate. Thus, the cellular alterations induced by transfection with Ha-T24-ras accelerate microfilament-dependent cytokinetic furrowing without significant effects on microtubule-dependent mitotic events. One of several possible mechanisms that could account for these observations involves a down regulation of protein kinase C which has been reported to occur in many neoplastic cells including those transformed by ras. Such a hypothesis could also have broader implications because it may be applicable to the increase in motility and metastatic activity generally observed in transformed cells.

Animals↗
PubMed1991

Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1.

Dopamine receptors belong to a superfamily of receptors that exert their biological effects through guanine nucleotide-binding (G) proteins. Two main dopamine receptor subtypes have been identified, D1 and D2, which differ in their pharmacological and biochemical characteristics. D1 stimulates adenylyl cyclase activity, whereas D2 inhibits it. Both receptors are primary targets for drugs used to treat many psychomotor diseases, including Parkinson's disease and schizophrenia. Whereas the dopamine D1 receptor has been cloned, biochemical and behavioural data indicate that dopamine D1-like receptors exist which either are not linked to adenylyl cyclase or display different pharmacological activities. We report here the cloning of a gene encoding a 477-amino-acid protein with strong homology to the cloned D1 receptor. The receptor, called D5, binds drugs with a pharmacological profile similar to that of the cloned D1 receptor, but displays a 10-fold higher affinity for the endogenous agonist, dopamine. As with D1, the dopamine D5 receptor stimulates adenylyl cyclase activity. Northern blot and in situ hybridization analyses reveal that the receptor is neuron-specific, localized primarily within limbic regions of the brain; no messenger RNA was detected in kidney, liver, heart or parathyroid gland. The existence of a dopamine D1-like receptor with these characteristics had not been predicted and may represent an alternative pathway for dopamine-mediated events and regulation of D2 receptor activity.

Amino Acid Sequence↗
PubMed1991

The impact of acoustic velocity variations on target detectability in ultrasonic images of the breast.

Experimentally obtained ultrasonic phase aberration profiles in the breast were used to investigate the impact of acoustic velocity variations on images of simulated breast lesions. The imaging properties of several phased-array transducers with varying frequencies and geometries were studied as phase error profiles of increasing magnitude were introduced. The targets studied were anechoic lesions of various sizes. The results indicate that phase aberrations significantly degrade the contrast of ultrasonic breast images, especially for high-resolution scanning systems.

Acoustics↗
PubMed1989

Survival patterns in clinical and angiographic subsets of medically treated patients with combined proximal left anterior descending and proximal left circumflex coronary artery disease (CASS).

Baseline, clinical, and angiographic features of 1014 Coronary Artery Surgery Study (CASS) registry patients with combined proximal left anterior descending and proximal left circumflex coronary disease were examined to define determinants of prognosis in this clinical high-risk patient subset. A stepwise Cox regression analysis identified congestive heart failure score, left ventricular contraction score, mitral regurgitation, age, and digitalis usage as independent variables predictive of 8-year survival. When patients were stratified by left ventricular contraction score, the 8-year survival rate was 62%, 49%, and 19%, respectively, for patients with a left ventricular score of 5 to 9, 10 to 14, and greater than or equal to 15 (p less than 0.0001). The presence of a stenosis greater than or equal to 70% in the right coronary artery was associated with worse survival (47% versus 54% at 8 years; p = 0.051). In conclusion, the diagnosis of combined proximal left anterior descending and left circumflex coronary artery disease represents a large prognostic spectrum that needs to be considered when counselling individual patients.

Coronary Angiography↗
PubMed1989

The role of exercise-induced silent myocardial ischemia in patients with abnormal left ventricular function. A report from the Coronary Artery Surgery Study (CASS) registry.

To evaluate the significance of ischemic ST depression without anginal chest pain (silent ischemia) during exercise testing among patients with abnormal left ventricular function, the data on 121 such patients with proven coronary artery disease (CAD) from the Coronary Artery Surgery Study (CASS) registry were analyzed. The patients with silent ischemia (group 1) were compared to: 124 CAD patients with both ST depression and angina (symptomatic ischemia, group 2); 159 CAD patients with neither ST depression nor angina (no ischemia, group 3); and 37 patients without CAD (controls). Survival at 7 years with medical therapy was similar for groups 1 (55%) and 2 (60%), but was substantially better for group 3 (73%, p = 0.001). Among group 1 patients with silent ischemia, survival was related to the severity of CAD (p = 0.001). Patients with silent ischemia and three-vessel CAD had a poor 7-year survival rate (37%) when treated medically. A comparable but non-randomized group of patients with silent ischemia and three-vessel CAD who underwent coronary artery bypass surgery had a much better 7-year survival rate (83%, p less than 0.0001). These results suggest that among patients with CAD and abnormal left ventricular function, silent ischemia adversely affects survival and can identify a higher risk subset of patients whose survival might be improved after coronary bypass surgery.

Coronary Disease↗