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D H Chui

Publications and source records attributed to D H Chui.

At least 55 records · Page 3Linked to original sources
PubMed1997

Prevalence and genotypes of alpha- and beta-thalassemia carriers in Hong Kong -- implications for population screening.

BACKGROUND: The thalassemias are common in southern China. We determined the prevalence of heterozygous carriers of these genetic disorders in Hong Kong and assessed the feasibility of a community-based screening program. METHODS: An educational and screening program for the thalassemias was carried out in three high schools with a total of 2420 students. Seventy-five percent of the students agreed to undergo screening, which consisted of blood counts, hemoglobin electrophoresis, serum ferritin measurements, and DNA analyses. RESULTS: Of the 1800 blood samples tested, 150 (8.3 percent) had microcytosis (mean corpuscular volume, <80 microm3). Ninety students (5.0 percent) were carriers of alpha-thalassemia, of whom 81 (4.5 percent) were carriers of the Southeast Asian type of deletion, in which both alpha-globin genes on the same chromosome 16 are deleted. Sixty-one students (3.4 percent) were carriers of either beta-thalassemia or the mutation coding for hemoglobin E. Six students were carriers of both alpha- and beta-thalassemias. On the basis of these figures, the estimated numbers of pregnancies in Hong Kong in which the fetus is at risk for homozygous alpha-thalassemia and beta-thalassemia major or intermedia are 145 and 80 per year, respectively. In Hong Kong the actual numbers of women referred for prenatal diagnoses of these disorders are approximately 95 and 40 per year, respectively. CONCLUSIONS: Despite the availability of hospital-based screening and prenatal diagnosis for many years in Hong Kong, many women carrying fetuses at risk for thalassemia are not referred for genetic counseling. A community-based program of education, screening, and counseling is needed in Hong Kong and southern China.

Adolescent↗
PubMed1997

De novo mutation of the beta-globin gene initiation codon (ATG-->AAG) in a Northern European boy.

We present a case of beta-thalassemia intermedia involving a 13-year-old boy of Northern European descent. His mother, father and older sister have normal hematologic indices. Molecular studies demonstrate that the proband carries a novel mutation of the beta-globin gene initiation codon (ATG-->AAG) which should give rise to beta(0)-thalassemia trait. The possibility of non-paternity was excluded, indicating that the novel mutation was the result of a de novo event. A review of the literature indicates that mutations involving the beta-globin gene initiation codon can give rise to a more severe phenotype than is generally associated with most other beta(+) or beta(0) mutations.

Adolescent↗
PubMed1995

Axonal degeneration promotes abnormal accumulation of amyloid beta-protein in ascending gracile tract of gracile axonal dystrophy (GAD) mouse.

The GAD mouse is a spontaneous neurological mutant with axonal dystrophy in the gracile tract of the medulla oblongata and spinal cord. The immunoreactivity of amyloid precursor protein (APP-IR) and amyloid beta-protein (A beta P-IR) was examined in the gracile tract and the dorsal root ganglia of normal and GAD mice. The mice were studied at 4, 9, 18, and 32 weeks of age. These periods correspond clinically to the initial, progressive, critical, and terminal stages of the disease, respectively. The APP-IR in both axons and glial cells was already accentuated to a higher level as early as 4 weeks of age in the gracile nucleus of GAD mouse. Similarly there was increase in APP-IR of GAD mouse in the dorsal root ganglia. Almost all of the primary neurons in the dorsal root ganglia at the lumbar cord level of GAD mouse revealed stronger APP-IR than those of normal mouse throughout all stages. The cells showing immunoreactivity for amyloid beta-protein became positive in axons and glial cells in the gracile nucleus by approximately the 9th week, and followed by an increase of A beta P-IR in order of the cervical, thoracic and lumbar spinal cords. These results suggest that the initial feature in GAD mouse is an accumulation of amyloid precursor protein induced by axonal dystrophy which then leads to a deposition of amyloid beta-protein within the cytoplasm of both axons and glial cells in the gracile tract.

Amyloid beta-Protein Precursor↗
PubMed1995

Demonstration of interleukin-3 receptor-associated antigen in the central nervous system.

We previously reported that interleukin-3 (IL-3) acts as a neurotrophic factor for cholinergic neurons. However, it has not yet been determined whether the action is derived from the interaction of IL-3 with IL-3 receptors. As the first step to study IL-3 receptors in the central nervous system, we examined the presence and localization of IL-3 receptor-associated antigen (IL-3RAA) in mouse and rat brain. Immunohistochemically, IL-3RAA, which is closely involved both in the IL-3 binding to IL-3 receptors and the tyrosine phosphorylation in the signal transduction for IL-3 in hematopoietic cells, was demonstrated in neurons throughout the brain. This was confirmed in primary cultured neurons and neuronal cell lines by immunocytochemistry and flow cytometry. The staining intensity varied among regions and the most intense immunoreactivity for IL-3RAA was found in large neurons in the magnocellular basal nuclei, pyramidal cells in the cerebral cortex, and neuronal cells in some nuclei of the brainstem. Not only cholinergic cell lines derived from the septal region but also other neuronal cell lines exhibited IL-3RAA immunoreactivity by flow cytometry. Therefore, we conclude that IL-3RAA is present in a wide variety of neurons in the brain including cholinergic neurons of the basal forebrain. Western blot analysis revealed that the candidates for IL-3RAA are 145, 100, and 50 kDa proteins both in neuronal and IL-3-dependent cell lines.

Animals↗
PubMed1995

Human embryonic zeta-globin gene expression in mouse-human hybrid erythroid cell lines.

The human alpha-globin-like embryonic zeta-globin chains are present in abundance during the first 5 to 6 weeks of gestation. Subsequently, zeta-globin chains are present in fetal blood at a very low level, which is supplanted by the expression of alpha-globin chains. Adult individuals who are carriers of the (--SEA/) alpha-thalassemia deletion, in contrast to normal adults, have low levels of embryonic zeta-globin chains in their circulating erythrocytes. In this investigation, we constructed stable mouse-human hybrid cells with murine erythroleukemia cells bearing human chromosome 16, with either the normal alpha-globin gene cluster (alpha alpha/) or the (--SEA/) type of alpha-thalassemia deletion. The results on the human zeta-globin gene expression in these hybrid cells indicate that murine adult erythroid transcription factors can induce the expression of human embryonic zeta-globin gene is cis to the (--SEA/) deletion, in parallel with the endogenous mouse alpha-globin gene expression. These data also show the importance of the DNA sequences within the (--SEA) deletion in regulating the expression of zeta-globin gene in cis during normal human hemoglobin ontogeny.

Animals↗
PubMed1995

cDNA cloning of murine Nrf 2 gene, coding for a p45 NF-E2 related transcription factor.

A lambda gt11 cDNA library was constructed from poly-A rich RNA prepared from circulating murine yolk sac derived nucleated erythroblasts, on day 9 of gestation. In addition to the embryonic globin genes, this library was found to contain clones for the hematopoietic specific p45 NF-E2, as well as p18 NF-E2 and p45 NF-E2 related factor 1 (Nrf 1) genes. Using a degenerate oligonucleotide 17mer probe coding for a part of the highly conserved DNA binding domain for p45 NF-E2, we have isolated murine Nrf 2, a second murine homologue related to p45 NF-E2. The murine Nrf 2 gene is expressed not only in erythroid cells, but also in the 3T3 murine fibroblast cell line.

Amino Acid Sequence↗
PubMed1995

Severity of beta-thalassemia due to genotypes involving the IVS-I-6 (T-->C) mutation.

Among individuals of Mediterranean or Middle Eastern descent, the IVS-I-6 (T-->C) mutation is one of the most common causes of beta-thalassemia. In this report, we describe the clinical phenotypes of a group of beta-thalassemia patients who are compound heterozygotes for the relatively mild IVS-I-6 (T-->C) beta-thalassemia mutation and more severe beta(+)- or beta (0)-thalassemia mutations. Although most of these patients are transfusion-dependent, the requirement for regular transfusions generally occurred late in childhood. A correlation between concomitant alpha-thalassemia and a mild transfusion-independent phenotype is not apparent, indicating the involvement of other ameliorating determinants.

Adult↗
PubMed1995

Comparison of haemoglobin H inclusion bodies with embryonic zeta globin in screening for alpha thalassaemia.

AIMS: To compare the haemoglobin (Hb) H inclusion test with immunocytochemical detection of embryonic zeta chains in screening for alpha thalassaemia. METHODS: Blood samples from 115 patients with relevant clinical history and hypochromic microcytic indexes were screened using the HbH inclusion test and the Variant Hemoglobin Testing System (BioRad, Hercules, CA, USA). RESULTS: The HbH inclusion test was positive in 61 of 115 cases, three of whom had HbH disease confirmed by electrophoresis. The remaining 58 had alpha thalassaemia 1. All three HbH cases and 56 of 58 cases of alpha thalassaemia 1 expressed embryonic zeta chains, giving a specificity of 96.7%. Fifty four of 115 cases had a negative HbH inclusion test, of whom 50 had beta thalassaemia trait and three had iron deficiency. No diagnosis was reached for the remaining patient. CONCLUSION: The immunocytochemical test is as sensitive as the HbH inclusion test in screening for alpha thalassaemia. The presence of zeta chains is highly specific for alpha thalassaemia 1 incorporating the (--/SEA) deletion. The specificity and simplicity of the immunocytochemical test make it the test of choice in screening for alpha thalassaemia.

Base Sequence↗
PubMed1995

Shark fin enriched diet prevents mucosal lipid abnormalities in experimental acute colitis.

Marine lipids contain eicosapentaenoic acid (EPA) which has anti-inflammatory effects. The aim of this research was to study, using the dextran sulfate induced acute colitis (AC) model, the effect of an EPA-rich shark fin supplemented diet on the mucosal lipid composition. The histology score increased in AC (p < 0.05), but only slightly in the EPA group. Similarly, colonic permeability to a intraluminally instilled water-soluble contrast medium significantly increased in the AC group, but not in EPA group. As compared with controls, the AC group showed lower levels of phosphatidylethanolamine, phosphatidylinositol, free fatty acid C20:5, and PL-FA C18:1 and C18:2 and higher levels of sphingomyelin, lysophosphatidylcholine, and C18:1 and free fatty acid C20:4 (p < 0.01) after 2 and 7 days. In the EPA group sphinogmyelin and lysophosphatidylcholine slightly increased and free fatty acid C20:4 decreased (p < 0.05) after 7 days, and no PL-FA change occurred. This study confirms the protective properties of EPA-rich marine food. EPA-enriched diet is protecting the colonic mucosa from the early derangements of lipid components occurring in this experimental AC model. This effect is likely to contribute to maintain an effective mucosal lining barrier.

Acute Disease↗
PubMed1995

[Ubiquitin immunoreactivity in the central nervous system of gracile axonal dystrophy (GAD) mouse].

In order to know the relationship of ubiquitin and axonal degeneration in the central nervous system (CNS) of the gracile axonal dystrophy (GAD) mutant mouse, the immunocytochemical study was performed in the spinal cord, medulla oblongata and brain of normal and GAD mice at 4, 9, 18 and 32 weeks of age. The polyclonal antibodies of ubiquitin were used for this study. The results were as follows: Many ubiquitin-positive dot-like structures (DS) were first observed in the gracile nucleus affected primarily with axonal degeneration. They extended to the gracile fasciculus on the dorsal part of spinal cord in accordance with the dying-back type degeneration. The second-order neurons at Clarke's nucleus were also affected slightly later stages and revealed ubiquitin-positive DS along the posterior spinocerebellar tract and the white matter of certain lobes of cerebellum. In 18th week, the transneuronal degeneration started from the distal axonal ends of the primary sensory neurons came up to the some parts of cortical neurons through the secondary neurons in the thalamus. The ubiquitin-positive DS were detected on the ventral surface of the medulla oblongata and increased progressively in number along the corticospinal (pyramidal) tract of spinal cord which consists of the descending fibers derived from the cortical neurons. These findings suggest that abnormal proteins in the degenerating axons were ubiquitinated rapidly before they accumulated in the preterminal axons whose neuron stems are far away from the place, and that GAD mouse would be a useful animal model to know the mechanism(s) of the naturally occurring transneuronal degeneration from the distal axonal ends of both ascending sensory neurons and descending pyramidal neurons in the CNS.

Animals↗
PubMed1994

Insulin-like growth factor II promotes in vitro cholinergic development of mouse septal neurons: comparison with the effects of insulin-like growth factor I.

We investigated the effect of insulin-like growth factors II and I (IGFII and IGFI) on septal primary cultures from mouse embryonic day 15 brains. The addition of IGFII to septal cultures enhanced total choline acetyltransferase (ChAT) activity in a dose-dependent manner. Maximal stimulation of ChAT activity was observed at 10 ng/ml IGFII. The effect of IGFII on ChAT activity was completely blocked by anti-IGFII/M-6-P receptor antibodies, whereas the antisera alone had no effect on the enzyme activity. Double-labeled immunohistochemical studies revealed that most ChAT-positive neurons expressed IGFII/M-6-P receptor immunoreactivity. These results indicate that the trophic effect of IGFII results from the direct action of this molecule through the IGFII/M-6-P receptor in septal cholinergic neurons. IGFI also stimulated ChAT activity, but with less potency than IGFII. Antibodies against the IGFII/M-6-P receptor inhibited approximately 50% of the IGFI response, suggesting that the effect of IGFI is mediated in part by the IGFII/M-6-P receptor. Thus, it appears that IGFII and IGFI are potent trophic factors for central cholinergic neurons and could potentially play a significant role in the differentiation, maintenance and regeneration of these neurons.

Animals↗
PubMed1994

DNA diagnosis of Hb S and Hb Caribbean (alpha 2 beta 2 91 Leu-->Arg) in a Jamaican family.

We describe a Canadian infant of Jamaican descent who presented with mild anemia. Hb electrophoresis revealed Hb S and an unknown Hb variant that migrated slightly faster than Hb S on cellulose acetate. Molecular studies of the family indicated that the proband is a compound heterozygote for Hb S and Hb Caribbean. Hb Caribbean has previously been characterized as a mildly unstable hemoglobin with low oxygen affinity, due to a Leu-->Arg substitution at amino acid residue 91. The present study establishes the molecular basis for Hb Caribbean (beta 91, CTG-->CGG) and confirms that Hb S/Hb Caribbean syndrome is not associated with serious clinical manifestations.

Adult↗