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Biomedical subjects

D H Chui

Publications and source records attributed to D H Chui.

At least 73 records · Page 4Linked to original sources
PubMed1994

Hb E/Hb LeporeHollandia in a family from Bangladesh.

We describe a family from Bangladesh in which three children are compound heterozygotes for Hb E (alpha 2 beta 2, beta 26Glu Lys) and Hb Lepore (delta-beta fusion gene). PCR amplification and direct nucleotide sequencing established that the fusion gene is Hb LeporeHollandia, with the cross-over localized to a 40 bp window between codon 22 and IVS-1 nt 16 of the delta- and beta-globin genes. This unusual combination of mutations is associated with a relatively mild clinical phenotype, with all three affected siblings having microcytic anemia of moderate severity without the need for transfusions.

Bangladesh↗
PubMed1994

Hb FM-Fort Ripley: confirmation of autosomal dominant inheritance and diagnosis by PCR and direct nucleotide sequencing.

We describe a normal neonate who presented at four days of age with asymptomatic cyanosis. There was no evidence of cardiac or pulmonary abnormality and an extended family history included 13 other affected family members with asymptomatic cyanosis lasting one to three months. Polymerase chain reaction (PCR) amplification and direct nucleotide sequencing of the proband's G gamma chain gene revealed the mutation at codon 92 (CAC-->TAC) previously shown in haemoglobin FM-Fort Ripley (alpha 2 gamma G gamma 92 (F8) His-->Tyr). This is the first family with Hb FM-Fort Ripley reported so far. It demonstrates autosomal dominant inheritance of this condition and incomplete penetrance.

Amino Acid Sequence↗
PubMed1994

Identification of a novel beta O-thalassaemia mutation in a Greek family and subsequent prenatal diagnosis.

We present a case in which a Greek couple was considered not to be at risk of having children with homozygous beta-thalassaemia, an assessment based largely on the father's belief that he carried alpha-thalassaemia. After their first child was diagnosed with homozygous beta-thalassaemia, the case was re-assessed and both parents were shown to have the haematological profile of beta-thalassaemia trait. Screening for the common Mediterranean mutations demonstrated that the mother carries the IVS-1 nt 110 G-->A beta(+)-thalassaemia mutation. Direct nucleotide sequencing of PCR-amplified DNA revealed that the father carries a novel beta O-thalassaemia mutation, frameshift codons 9/10 (+T). The couple's second pregnancy was terminated after prenatal testing revealed that the fetus had inherited both parental mutations. This case illustrates the need to confirm the carrier status of individuals prior to assessing their genetic risks, and highlights the importance of being able to identify rare or novel beta-thalassaemia mutations.

Base Sequence↗
PubMed1994

Anti-zeta antibody screening for alpha-thalassemia using dried filter paper blood.

The most common alpha-thalassemia in Southeast Asian or Southern Chinese populations is the (--SEA) double alpha-globin deletion. Couples heterozygous for (--SEA) have 25% risk for hydrops fetalis from loss of all four alpha-globin genes. The (--SEA) deletion spares the embryonic zeta-globin genes and causes traces of zeta-peptide to persist throughout life. A colorimetric monoclonal anti-zeta antibody test for raised zeta-peptide has detected the (--SEA) deletion in liquid blood samples, but not deletions of the entire alpha-globin region with loss of the zeta-globin genes. Eluates from dried blood spots had the same anti-zeta antibody color reaction as whole blood, even after storage at 4 degrees C for up to 77 days. The anti-zeta antibody test was positive in 24 of 91 microcytic samples (mean corpuscular hemoglobin < 24 pg), including four with iron deficiency; it was negative in 26 provisionally diagnosed alpha-thalassemia-1 heterozygotes and all 32 nonmicrocytic samples. Southern blot analysis and a specific SEA-polymerase chain reaction test confirmed that 18 anti-zeta antibody-positive samples and 1 anti-zeta antibody-negative sample had the (--SEA) deletion. Two anti-zeta antibody-negative microcytic samples had the (--Fil) total alpha-globin region deletion, 2 had single alpha-gene deletions, 22 others may also have had a total alpha-region deletion. Hence specificity was very high and sensitivity was 95%. The anti-zeta antibody test can detect the (--SEA) deletion in dried blood samples, even after prolonged storage. This simple inexpensive test can conveniently screen samples collected at a distance from a central laboratory.

Antibodies, Monoclonal↗
PubMed1994

Filipino beta-thalassemia due to a large deletion: identification of the deletion endpoints and polymerase chain reaction (PCR)-based diagnosis.

The gene frequency of beta-thalassemia among Filipinos is estimated to be 0.02, although little is known about the mutations involved. Recently, an extensive beta-thalassemia deletion was reported in several unrelated individuals of Filipino descent. The deletion begins approximately 4 kb upstream of the beta-globin gene, and extends 3' beyond the beta-globin gene. In this report, we identify the 5' and 3' deletion endpoints and present a polymerase chain reaction (PCR) strategy for rapid DNA diagnosis of the Filipino beta-thalassemia deletion.

Base Sequence↗
PubMed1994

Nafamostat mesilate on the course of acute pancreatitis. Protective effect on peritoneal permeability and relation with supervening pulmonary distress.

Three hundred sixty Sprague-Dawley rats were allocated into four groups, according to different content of a 24-h i.v. infusion performed 1 h after intrabiliary injection of enterokinase/sodium taurocholate to induce acute pancreatitis (AP): (1) Saline; (2) 5 micrograms/kg/h nafamostat mesilate (FUT-175); (3) 10 micrograms/kg/h FUT-175; and (4) 25 micrograms/kg/h FUT-175. Peritoneal fluid was removed and exchanged with 1 mL 3.33 M fluorescein-isothiocyanate-conjugated (FITC) dextrans of 4000-40,000 Dalton. Serial blood samples were withdrawn and examined for FITC-dextrans, phospholipase A2 (PLA2), blood gases, amylase, and lipase. As compared to control (55%), FUT-175 brought about a lower (5 micrograms/kg/h: 25%) or no mortality (10 and 25 micrograms/kg/h), and a milder histological and biochemical evidence of AP. Untreated animals with PLA2 values over two times the standard deviation showed a respiratory distress. Further, unlike group 1, FUT-175 doses as low as 5 micrograms/kg prevented the increase in peritoneal permeability to small-size molecules (up to 20,000 Dalton). In a second experiment under the same drug protocol, 1000 U/mL of PLA2 and 2 mL of pancreatitis ascites were instilled ip. Peritoneal permeability to FITC-dextrans up to 30,000 Dalton and to PLA2 significantly increased in the saline group and in the 5 micrograms/kg FUT-175 group. However, 10 micrograms/kg and 25 micrograms/kg FUT-175 doses prevented such phenomenon. In conclusion, FUT-175 proves to be a potent antiprotease molecule with a biochemical activity also against PLA2 in vivo and prevents significant transperitoneal-blood access of pancreatic enzymes.

Acute Disease↗
PubMed1994

Decreased beta-amyloid and increased abnormal Tau deposition in the brain of aged patients with leprosy.

We examined the brains of 37 leprosy patients (mean age, 76.3 +/- 7.8 years), 5 patients with Alzheimer-type dementia (mean age, 79.0 +/- 9.5 years), and 23 age-matched non-dementia controls (mean age, 77.6 +/- 5.4 years). The frequency of beta-amyloid (A beta)-positive cases was lower (27.0%) in leprosy patients (n = 37) than in controls (47.8%; P = 0.05, Z = 1.49). When senile plaque subtypes were examined, type III (classical) plaques were significantly fewer (P < 0.05) in leprosy subjects compared with controls. Interestingly, neurofibrillary tangles in the temporal cortex were much more frequent in leprosy patients than in controls (P < 0.05). However, hippocampal CA3 pyramidal neurons in leprosy patients were well preserved. These data indicate that 1) leprosy patients have a low risk of A beta deposition but a high risk of abnormal tau deposition, 2) abnormal tau deposition is unrelated to A beta deposition in leprosy, and 3) neuronal loss is unrelated to abnormal tau deposition. It is not clear at present whether the result is related to the disease process itself, antileprosy treatment, environmental factors, or the genetic background in leprosy patients.

Aged↗
PubMed1993

Immunocytological test to detect adult carriers of (--SEA/) deletional alpha-thalassaemia.

The gene frequency for (--SEA/) deletional alpha-thalassaemia is high in Southeast Asian populations. We report a simple immunocytological test that is highly sensitive and specific for the detection of adult carriers of the (--SEA/) deletion. We prospectively studied 206 consecutive adult blood samples. All 41 with the (--SEA/) deletion had a positive test; all but 1 of the 165 non-carriers were negative. This test, whose major requirement is a fluorescence microscope, should be useful to identify couples at risk of conceiving fetuses with homozygous alpha-thalassaemia.

Adult↗
PubMed1993

Trophic effect of erythropoietin and other hematopoietic factors on central cholinergic neurons in vitro and in vivo.

In vitro granulocyte colony-stimulating factor (G-CSF), macrophage colony-stimulating factor (M-CSF), erythropoietin (EPO), and erythroid differentiation factor (EDF) augmented choline acetyltransferase (ChAT) activity in mouse embryonic primary septal neurons and in cholinergic hybridoma cell line, SN6.10.2.2. This is similar to the effects seen with interleukin-3 (IL-3) or granulocyte-macrophage colony-stimulating factor (GM-CSF). Moreover, in vivo GM-CSF and EPO promoted survival of septal cholinergic neurons in adult rats which had undergone fimbria-fornix transections. These results suggest that some of the hematopoietic factors act on cholinergic neurons as 'neurotrophic factors' to influence the differentiation, maintenance and regeneration of these neurons.

Animals↗
PubMed1993

Expression of embryonic zeta-globin and epsilon-globin chains in a 10-year-old girl with congenital anemia.

A 10-year-old Danish girl with congenital anemia is described. At birth, she had severe anemia and erythroblastosis and was transfused a number of times during the first year. The need for transfusions has since declined steadily. Her reticulocyte counts varied between 2% and 15%, and her bone marrow aspirate showed some dyserythropoietic features. Her hemoglobin F level was consistently elevated, up to as much as 41%. Her erythrocytes had a normal level of I antigen but an undetectable level of i antigen. Moreover, embryonic zeta-globin and epsilon-globin chains were present in some of her circulating erythrocytes. These findings may represent the manifestations of a new variant of congenital anemia.

Adolescent↗
PubMed1993

Detection of the (--SEA) double alpha-globin gene deletion by a simple immunologic assay for embryonic zeta-globin chains.

Homozygous alpha-thalassemia [alpha-thal-1], with loss of all four alpha-globin genes, causes lethal hydrops fetalis. The most common mutation producing this syndrome is the Southeast Asian (--SEA) double alpha-globin gene deletion. Erythrocytes from adults heterozygous for the (--SEA) deletion have minute amounts of embryonic zeta-globin chains detectable by anti-zeta-globin monoclonal antibodies. Among 225 peripheral blood samples tested by a simple anti-zeta-immunobinding tetrazolium dye test, 81 were positive and 144 were negative. The majority of subjects were of Filipino, Chinese, or Laotian ancestry. All 81 positive samples were confirmed by Bam HI digests and a zeta-cDNA probe to have the (--SEA) mutation. The (--SEA) double alpha-deletion was the only abnormality in 58. In the others, it was combined with alpha-globin or beta-globin mutations, or coincidental iron deficiency. Four other samples from (--SEA) heterozygotes were negative by this immunologic assay. Anti-zeta negative samples included 78 deletions of the total alpha-globin region, (--Tot), 23 single alpha-globin deletions, and a variety of beta-globin mutations; 16 normocytic samples with normal alpha-genes were also negative. Ten anti-zeta positive and 25 anti-zeta negative samples had benign triplicated zeta-globin genes. In this population, the sensitivity of this test was 95%; and specificity for the (--SEA) mutation was 100%. Anti-zeta immunobinding testing provides rapid, simple, and reliable screening for the (--SEA) double alpha-globin deletion, although it does not detect the (--Tot) total alpha-deletions.

Antibodies, Monoclonal↗
PubMed1993

Identification of two novel beta zero-thalassemia mutations in a Filipino family: frameshift codon 67 (-TG) and a beta-globin gene deletion.

The frequency of beta-thalassemia alleles among Filipinos is estimated to be 0.02, although little is known about the actual mutations represented in this population. Here, we describe a Filipino family in which a child has severe beta-thalassemia major. Molecular studies of the family revealed that the proband is a compound heterozygote for two previously unreported beta zero-thalassemia alleles: a frameshift mutation (-TG) at codon 67 and a deletion of the entire beta-globin gene. The 5' endpoint of this novel deletion is located approximately 3.9 kb to approximately 4.3 kb upstream of beta-globin gene, and the deletion extends 3' beyond the beta-globin gene for an undetermined distance. The occurrence of two novel beta-thalassemia alleles in a single family suggests that the Filipino population may have a unique spectrum of beta-thalassemia alleles.

Alleles↗
PubMed1993

Duodenal bicarbonate secretion induced by human epidermal growth factor in rats is partially mediated by prostaglandins.

In the present study, the effect of graded intravenous infusions of human epidermal growth factor (hEGF) 0.005, 0.05 and 0.25 micrograms/ml, with or without 4 mg/kg i.p. indomethacin pretreatment, on rat duodenal bicarbonate secretion was investigated. Perfused duodenal loops were prepared in rats which were given intravenous infusions of hEGF with or without indomethacin. Duodenal pH and pCO2 were measured at 5-min intervals for 45 min, and bicarbonate secretion was calculated. Compared to control, each dose of hEGF caused a significant dose/response rise of duodenal bicarbonate secretion. Prostaglandin release was abolished by indomethacin pretreatment. Indomethacin-pretreated rats had a significant reduction of bicarbonate secretion which was still higher than in controls. These results provide evidence that duodenal bicarbonate secretion induced by hEGF is only partly accounted for by a prostaglandin-dependent mechanism.

Animals↗
PubMed1993

Carrier detection and prenatal diagnosis of hemoglobinopathies in Ontario.

The province of Ontario has a total population of approximately 10 million people, with approximately 20% being of African, Southeast Asian, East Indian, Mediterranean, or Middle Eastern ancestry in whom the gene frequency for hemoglobinopathies is relatively high. In 1989, the Ontario Ministry of Health funded the establishment of the Provincial Hemoglobinopathy DNA Diagnostic Laboratory located at the McMaster University Medical Centre in Hamilton, Ontario. The Laboratory provides DNA analysis to identify the globin gene mutations in carriers and affected individuals, and performs prenatal diagnosis for severe hemoglobinopathies. Annually, more than 400 patient samples are referred to the Laboratory for investigation, of which 25-35 are fetal samples from pregnancies at risk for either homozygous alpha-thalassemia, beta-thalassemia major, or sickling disorders. We have detected more than 70 different globin gene mutations, including several mutations not previously reported in the literature. Here we present examples of the approaches used to detect globin gene mutations in a heterogeneous "at risk" population such as in Ontario, and discuss the impact of this service on patient care, genetic counselling, and the incidence of severe hemoglobinopathies in Ontario.

DNA↗
PubMed1992

Human embryonic zeta-globin chain expression in deletional alpha-thalassemias.

zeta-Globin chain expression in carriers of a number of deletional alpha-thalassemias is investigated by radioimmunoassay. In a few cases, zeta-globin mRNAs are also studied. zeta-Globin chains are detected in (--SEA/), (--MED/), and (--SPAN/) deletions, but not in six other deletional mutations. These results suggest that the DNA element capable of suppressing zeta-globin expression in adult erythroid cells is present within the (--SPAN/) deletion, while the DNA fragment between the 5' breakpoints of the (--SA/) and the (--SEA/) deletions may contain sequences necessary for augmenting zeta-globin expression in adult erythroid cells. Furthermore, zeta-globin chains are shown by an immunocytologic technique to be present in all circulating erythrocytes in carriers of the (--SEA/) and (--MED/) deletions. This simple immunocytologic test is highly sensitive and specific to detect adult carriers of either the (--SEA/) or (--MED/) deletions, and can be used for the detection of couples at risk of pregnancies involving fetuses with homozygous alpha-thalassemia.

Chromosome Deletion↗
PubMed1992

Stress induces neuronal death in the hippocampus of castrated rats.

Whereas loss of CA3 neurons in the hippocampus of monkeys which died of stress ulcers suggests that some structural changes may occur, there is no direct evidence that shows stress-induced irreversible changes of neurons. When rats were orchidectomized (castrated) and stressed by restraint and immersion in water for 15 min/day for 30 days, significant loss of hippocampal CA3 and CA4 neurons was observed. Furthermore, primary cultured hippocampal neurons survived shorter when treated with corticosterone. This neuronal loss was prevented by simultaneous administration of testosterone in vivo and in vitro. These findings indicate that stress can contribute to neuronal degeneration associated with hypogonadal conditions such as aging.

Androstanols↗
PubMed1992

Two novel beta-thalassemia mutations in the 5' and 3' noncoding regions of the beta-globin gene.

Two novel beta-thalassemia mutations are described. The first mutation, found in an Italian family, is a G----A substitution in nucleotide (nt) +22 relative to the beta-globin gene Cap site. This mutation creates a cryptic ATG initiation codon, the utilization of which for translation would result in premature termination 36 bp 3' downstream. The second mutation, found in an Irish family, is a T----C substitution in nt +1570, or 12 bp 5' upstream of the AATAAA polyadenylation signal in the 3' noncoding region. It is postulated that this mutation leads to destabilization of the encoded beta-globin mRNA.

Adult↗