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B Eng

Publications and source records attributed to B Eng.

At least 37 records · Page 2Linked to original sources
PubMed1994

Genetic linkage studies in antithrombin-deficient kindreds using a highly polymorphic trinucleotide short tandem repeat (STR) within the human antithrombin gene.

PCR amplification and analysis of short tandem repeats (STR) have provided a useful tool for genetic linkage studies and for the diagnosis of genetic disorders. We have recently identified a novel trinucleotide STR, (ATT).(TAA), in the fifth intron of the human antithrombin gene (AT3) located on chromosome 1q23. PCR amplification, cloning, and sequence analysis revealed this AT3-STR to be highly polymorphic with repeat units ranging in size from (ATT)5 to (ATT)18. Ten distinct alleles were found in 81 unrelated Caucasian individuals (162 alleles) with an observed heterozygosity of 81%. Genetic linkage studies using the AT3-STR in two previously described antithrombin (AT)-deficient kindreds, AT-Hamilton (Ala 382 Thr) and AT-Amiens (Arg 47 Cys), demonstrate, in a given kindred, that a specific AT3-STR polymorphism is strongly associated with a particular AT mutation. Thus, this highly polymorphic AT3-STR should be very useful in performing linkage studies in AT-deficient kindreds as well as in investigating other chromosome 1-related genetic disorders.

Antithrombins↗
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↗
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

Trinucleotide repeat polymorphism within the human antithrombin gene (AT3): allele frequency data for three population groups.

The fifth intron of the human antithrombin gene (AT3) of chromosome 1q23 contains a highly polymorphic short tandem repeat based on the trinucleotide repeat [ATT]. Alleles range in size from [ATT]5 to [ATT]18, and can be typed using the polymerase chain reaction. Here we report allele frequency population data for Caucasians, Blacks and Southeast Asians. Statistical analyses demonstrate consistency with Hardy-Weinberg equilibrium for all three databases, and that the allele frequencies of all three population groups are significantly different from each other. This locus reveals 76% to 87% heterozygosity and therefore may be useful for forensic identity testing and paternity determination.

Alleles↗
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

Beta-thalassemia intermedia in a Lebanese child due to homozygosity for the -88 (C-->T) mutation.

We report a case of beta-thalassemia intermedia involving a 3-year-old male child of Lebanese descent. Molecular studies of the family showed that he is homozygous for the -88 (C-->T) beta (+)-thalassemia mutation. This mutation is the second most common cause of beta-thalassemia in Black populations, and has also been reported in Asian Indians. A review of Lebanese beta-thalassemia cases revealed considerable mutation heterogeneity and excess homozygosity due to consanguinity.

Adult↗
PubMed1994

Delta beta-thalassemia in an African-American: identification of the deletion endpoints and PCR-based diagnosis.

We describe an African-American child with beta-thalassemia intermedia. Molecular studies revealed that the proband is a compound heterozygote for the -29 (A-->G) beta (+)-thalassemia mutation and an extensive deletion involving the delta- and beta-globin genes. The proband's mother is a simple carrier of the deletion and exhibits the phenotype of delta beta-thalassemia rather than hereditary persistence of fetal hemoglobin. The deletion spans 11,767 bp, with the 5' deletion endpoint located 2,455 bp upstream of the delta-globin gene mRNA Cap site and the 3' endpoint located 441 bp downstream of the termination codon of the beta-globin gene. Based on this information, we have developed a polymerase chain reaction strategy for the rapid detection of this delta beta-thalassemia deletion.

Adult↗
PubMed1994

Anomalous migration of PCR products using nondenaturing polyacrylamide gel electrophoresis: the amelogenin sex-typing system.

Sex-typing of biological samples can be accomplished using the polymerase chain reaction (PCR) to amplify DNA sequences that are specific for the Y-chromosome. One such system is based on PCR amplification of the X-chromosome amelogenin gene and the amelogenin-like sequences located near the centromere of the Y-chromosome. The X and Y PCR products can be distinguished from each other on the basis of a 177 basepair (bp) insertion in the X relative to the Y. In this report, we demonstrate that the amelogenin PCR products migrate anomalously using non-denaturing polyacrylamide gel electrophoresis (ND-PAGE) as opposed to agarose gel electrophoresis or denaturing PAGE. These results may be relevant to the choice of electrophoretic system used to analyze highly polymorphic loci for individual identification.

Amelogenin↗
PubMed1994

Sensitivity of radionuclide bolus transport and videofluoroscopic studies compared with manometry in the detection of achalasia.

OBJECTIVE: The sensitivity of radionuclide bolus transport and videofluoroscopic studies to confirm manometrically revealed achalasia was investigated prospectively in 77 patients with symptoms indicative of disordered esophageal motor function. METHODS: The studies were performed in random order and were analyzed blindly by strict diagnostic criteria. Transport of radiolabeled water was recorded for 2 min with patients supine. Videofluoroscopy assessed three swallows in prone oblique and one in upright position. Manometry employed four pressure sensors in the esophageal body and the Dent sleeve in the lower esophageal sphincter. RESULTS: Radionuclide and videofluoroscopic studies confirmed 25 and 15, respectively, of 37 manometrically diagnosed achalasias and provided indications for the disorder in another 8 and 16 patients. Using information from both studies increased the sensitivity to detect achalasia from 68% and 41%, respectively, to 73%, and increased detection of disordered esophageal motor function from 81% and 74% to 92%. CONCLUSION: Radionuclide and videofluoroscopic studies represent valuable and complementary, although relatively insensitive, procedures to detect achalasia.

Colloids↗
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

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

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

Integrin receptors and function on cultured glomerular endothelial cells.

Integrin expression and function on a cloned line of rat glomerular endothelial cells (GEndoC) were studied in an effort to obtain a better understanding of the means by which these cells interact with components of the glomerular basement membrane. Cultured GEndoC adhered to fibronectin, laminin and types I and IV collagen and expressed alpha 1 beta 1, alpha 2 beta 1, alpha 3 beta 1, alpha 5 beta 1, alpha v beta 1 and alpha v beta 3 integrins. Synthetic RGDS peptides significantly decreased adhesion to fibronectin (53.1 +/- 4.7% of control). Antibody to rat beta 1 integrin strongly inhibited adhesion to laminin, fibronectin and types I and IV collagen (11.2, 19.0, 67.3 and 31.9% of control adhesion, respectively), while antibody to the rat alpha 1 integrin chain strongly inhibited adhesion to laminin (65.2% of control), but only mildly inhibited adhesion to type IV collagen (77.2% of control) and did not affect adhesion to type I collagen (97.8% of control). Affinity chromatography of GEndoC lysates on a column of immobilized type I collagen displayed predominantly binding of alpha 3 beta 1 integrin with trace amounts of alpha 1 beta 1 and alpha 2 beta 1, documenting the major role of alpha 3 beta 1 in GEndoC adhesion to collagen. Chromatography on the immobilized cell-binding fragment of fibronectin revealed the alpha 5 beta 1 integrin to be the major fibronectin receptor on these cells, but antibody to alpha v beta 3 integrin also documented a minor role for alpha v beta 1 or alpha v beta 3 in fibronectin adhesion.(ABSTRACT TRUNCATED AT 250 WORDS)

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↗
PubMed1993

Survey of nursing research programs in children's hospitals.

Available published literature describing successfully implemented research programs is relatively limited, particularly within children's hospitals. In order to determine the status of research program development within children's hospitals, a mailed survey was sent to 108 free-standing children's hospitals in the United States and Canada. The questionnaire was comprised of questions pertaining to five general sections: (a) institutional demographics; (b) organizational structure for research; (c) research activities; (d) relationship to other agency research; and (e) demographic characteristics of the individual completing the survey. Findings indicated that nursing research within children's hospitals is in an early development state, but that it is recognized as a necessary and credible component of nursing. Differences were noted between the groups of hospitals with the most research activity and those with no research activity. Hospitals were in various stages of research development, a sequential process characterized by a sequential pattern comprised of two phases.

Canada↗