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B J McCarthy

Publications and source records attributed to B J McCarthy.

At least 37 records · Page 2Linked to original sources
PubMed1997

Data linkage methods used in maternally-linked birth and infant death surveillance data sets from the United States (Georgia, Missouri, Utah and Washington State), Israel, Norway, Scotland and Western Australia.

In this paper we describe the methods used to link birth and infant mortality and morbidity surveillance data sets into sibships using deterministic or multistage probabilistic linkage methods. We describe nine linked data sets: four in the United States (Georgia, Missouri, Utah and Washington State), and four elsewhere (Scotland, Norway, Israel and Western Australia). Norway and Israel use deterministic methods to link births and deaths into sibships. The deterministic linkage is usually dependent on the availability of national identification numbers. In both countries they assign these numbers at birth. Deterministic linkage is usually highly successful, and the major problem is the validation of linkages. In the United States, Western Australia and UK linkage is multistage and probabilistic. This approach is usually dependent on the calculation linkage weights from sociodemographic variables. The success rates of probabilistic methods are above 80%. Maternally-linked perinatal data open new vistas for epidemiological research. Recurrence of poor perinatal outcomes is more appropriately studied using longitudinally-linked data sets. In addition, the emergence of risk factors and the recurrence of risk factors can be studied.

Epidemiologic Methods↗
PubMed1997

The relationship of interpregnancy interval to infant birthweight and length of gestation among low-risk women, Georgia.

To examine the association between interpregnancy interval and low birthweight (< 2500 g), preterm delivery (< 37 weeks' gestation), and inadequate fetal growth, we studied a population-based sample of 23,388 white and 4885 black women at low risk for adverse pregnancy outcomes who delivered their first and second infants in Georgia from 1980 to 1992. We used fetal death and livebirth certificates. The interpregnancy interval was the time from delivery to the woman's next conception. For each pregnancy outcome, we stratified by race and used logistic regression to assess the association between interpregnancy interval and outcome, while controlling for confounders. Intervals < 6 months were observed for 3.7% of white women and 7.0% of black women and intervals > or = 48 months were seen for 16.8% of white women and 24.8% of black women. Results from logistic regression showed that, for both races, interpregnancy interval was associated with low birthweight and preterm delivery. Nearly all of the increased risk occurred in intervals < 6 months or > or = 48 months. The magnitude of the increase in risk associated with these intervals ranged from modest to moderate and was similar for black and white women. Because short interpregnancy intervals are rare and are weak risk factors among low-risk women, efforts to lengthen interpregnancy intervals are unlikely to reduce substantially their rates of adverse pregnancy outcomes.

Adult↗
PubMed1997

Evaluation of reproductive histories constructed by linking vital records.

We used 1.4 million fetal death and birth certificates filed in Georgia between 1980 and 1992 to construct 369,686 chains of two or more reproductive events occurring to the same woman. We evaluated these chains using both information on the certificates and information independently collected in interviews with 1311 women. Overall, 86.6% of the chains had the expected number of events, based on the certificate's information about previous pregnancies. Seventy-nine per cent of the chains had the expected number of events based on the maternal interviews. Consistency between the observed number of events in the chain and the number expected, based either on data from the certificates or from the maternal interviews, was greatest for chains with two or three events. Mothers born in Georgia were more likely to have complete chains than mothers born elsewhere. Among the 551,391 non-linked certificates, 48.7% were the mother's first birth, 40.2% were second or higher-order births to women whose previous pregnancy occurred before 1980, and 11.1% were second or higher-order births to women whose previous pregnancy occurred after 1980. Fetal death and livebirth certificates can be linked to construct pregnancy histories with reasonably low levels of underlinkage and overlinkage.

Adult↗
PubMed1997

Molecular epidemiology of autoimmune thyroid disease.

This paper presents preliminary data regarding the prevalence and risk factors for autoimmune thyroid disease in IDDM probands ascertained from the Children's Hospital of Pittsburgh IDDM Registry for 1950-1965 (n = 669). Living IDDM probands who participated in the 1990 follow-up survey (n = 380) were recruited for the Familial Autoimmune and Diabetes Study. Siblings and parents were also invited to participate. To date, 255 IDDM probands and 597 parents and siblings have been evaluated. The diagnosis of autoimmune thyroid disease was based on a clinical evaluation, medical history, and laboratory determinations. Graves disease was rare in this cohort (n = 5). However, Hashimoto's thyroiditis was common among women. Prevalence rates ranged from 54% for IDDM women age < 40 years to 75% for those > 50 years. Corresponding age-specific estimates for female relatives were 22% and 44%, respectively. Approximately one-half of the Hashimoto's individuals were euthyroid; they were more likely to have other autoantibodies and a positive family history than those who were hypothyroid or had no thyroid disease. Genetic analyses revealed a 2-fold increase in DQA1*0501-DQB1*0201 among the Hashimoto's compared to the non-Hashimoto's haplotypes. These findings suggested that Hashimoto's thyroiditis was common in IDDM families, which may be due, in part, to common disease susceptibility genes.

Adolescent↗
PubMed1992

Polymorphism of human glycoprotein Ib alpha results from a variable number of tandem repeats of a 13-amino acid sequence in the mucin-like macroglycopeptide region. Structure/function implications.

Four polymorphic variants of the platelet receptor for von Willebrand factor, glycoprotein Ib, have been described that differ in molecular weight on sodium dodecyl sulfate-polyacrylamide gels (Moroi, M., Jung, S. M., and Yoshida, N. (1984) Blood 64, 622-629). A recent report localized the polymorphic site to the heavily O-glycosylated region of the glycoprotein Ib alpha-chain known as the macroglycopeptide (Meyer, M., and Schellenberg, I. (1990) Thromb. Res. 58, 233-242). This region contains several tandem repeats of a mucin-like sequence, which appeared to be a likely site for polymorphic variation. We amplified genomic DNA corresponding to the macroglycopeptide from 206 individuals from four ethnic groups and identified three length variants based on the migration of the amplified DNA on denaturing polyacrylamide gels. DNA sequencing revealed that the three variants represented four alleles, two of which varied by only one base pair, a difference that did not result in an amino acid change. The three length variants differed in the number of tandem repeats of a 39-base pair sequence that results in perfect duplication of a 13-amino acid sequence that originated within a region flanked by Glu-396 and Thr-411. The smallest isoform contained one such sequence; the next largest, two repeats; and the largest, three repeats. The DNA sequence containing the tandem repeats was flanked by direct repeats typical of the target site duplications found flanking transposed DNA, suggesting a mechanism for acquisition of this region by the primordial glycoprotein Ib alpha precursor. The amino acid sequence of the repeated element that accounts for the polymorphism contained five sites for potential O-glycosylation, which together with the repeated amino acids would result in incremental differences in molecular weight of approximately 6,000 between the different isoforms. The addition of repeats to the macroglycopeptide is predicted to increase the length of this elongated glycosylated region and extend the distance between the ligand-binding domain of glycoprotein Ib and the platelet plasma membrane, an effect that would project the ligand-binding domain farther into the bloodstream. Such a change may alter the susceptibility of platelets to shear-induced activation, a process that requires an interaction between glycoprotein Ib and von Willebrand factor.

Amino Acid Sequence↗
PubMed1992

Synthesis and secretion of apolipoprotein E occur independently of synthesis and secretion of apolipoprotein B-containing lipoproteins in HepG2 cells.

The synthesis and secretion of apolipoprotein (apo) E, a major protein component of very low density lipoproteins, were examined in the human hepatoma cell line HepG2 under metabolic conditions known to stimulate lipogenesis and the production of apoB-containing lipoproteins. When HepG2 cells were incubated in the presence of fetal bovine serum (5 or 10%) or canine chylomicron remnants (5 or 10 micrograms of protein), the secretion of triglycerides and cholesteryl esters of lipoproteins of d less than 1.063 g/ml increased, as determined by the incorporation of [14C]acetate. Determination of the distribution of apoE among media lipoproteins by agarose column chromatography showed that the majority of secreted apoE was associated with large lipoproteins when cells were incubated with fetal bovine serum. However, immunoblot analysis of total media apoE revealed that incubating cells with or without the lipogenic factors had no effect on the amount of apoE secreted. Pulse-chase and continuous labeling experiments demonstrated that the synthesis and secretion of apoE did not vary under the different metabolic conditions, even though there was a 5-fold increase in apoB secretion in response to increased lipogenesis. Neither apoE nor apoB mRNA levels responded to the lipogenic stimuli. We conclude that the synthesis and secretion of apoE are independent of the production of apoB-containing lipoproteins in HepG2 cells.

Acetates↗
PubMed1992

Elimination of apolipoprotein B48 formation in rat hepatoma cell lines transfected with mutant human apolipoprotein B cDNA constructs.

Rat hepatoma McA-RH7777 cell lines transfected with full-length human apolipoprotein (apo) B constructs produce mostly human apoB48 and only small amounts of apoB100, as a result of mRNA editing at codon 2153 (C to U conversion at nucleotide 6666). To abolish the formation of apoB48 and increase the yield of apoB100 and other forms of apoB longer than apoB48, site-specific mutations were introduced at or near the site of apoB mRNA editing. Among four mutations examined, only that in which codon 2153 was converted from CAA (Gln) to CTA (Leu) effectively precluded the formation of apoB48. In this mutant, a stop codon would not be generated even if the C to U conversion occurred. The three other mutations were introduced to disrupt the proposed stem-loop structure encompassing the editing site. Changes made in the third positions of five codons on the 5' side of the edited base or of four codons 3' of the edited base failed to eliminate the production of a protein with the approximate size of apoB48. A construct in which codon 2153 was changed from CAA to GAT (Asp) also failed to eliminate the production of a protein the size of apoB48. Analysis of the region between nucleotides 6200 and 6900 of the cDNA did not detect any prevalent alternate editing sites. Immunoblot analysis using polyclonal antibodies raised against synthetic peptides of human apoB100 indicated that the carboxyl terminus of the apoB48-like proteins probably resides between amino acid residues 2068 and 2129 of apoB100. These results provide some insight into the mechanism of apoB mRNA editing and will facilitate further studies on apoB-containing lipoproteins.

Amino Acid Sequence↗
PubMed1991

Expression of carboxyl-terminally truncated forms of human apolipoprotein B in rat hepatoma cells. Evidence that the length of apolipoprotein B has a major effect on the buoyant density of the secreted lipoproteins.

We examined the relationship between the size of human apolipoprotein (apo) B and the formation and secretion of apoB-containing lipoprotein particles. Stable transformants of the rat hepatoma cell line McA-RH7777 harboring a variety of human apoB cDNA constructs were established, and these produced carboxyl-terminally truncated apoB proteins (apoB18, -B23, -B28, -B31, -B48, and -B53). Immunoblotting of apoB proteins secreted into the culture medium and fractionated by equilibrium density ultracentrifugation revealed that each of the truncated apoB species was secreted from the cells. The peak densities of the apoB-containing particles decreased as the length of the apoB proteins increased. Apolipoproteins B18 and B23 appeared at the bottom of the salt gradient (d = 1.23 g/ml), whereas particles containing apoB28, -B31, -B37, -B48, and -B53 exhibited progressive decreases in density. The density distribution of secreted apolipoproteins was not affected by the expression or secretion of these recombinant apoB species. As determined by nondenaturing gel electrophoresis, apoB28, -B31, -B37, -B48, and -B53 formed their own discrete particles, and there was a direct correlation between the size of the particles and the length of the apoB species. The efficiency and rate of secretion of these truncated forms of apoB were studied by measuring the decrease of immunoprecipitated 35S-labeled apoB proteins in the cells and their accumulation in the medium. Proteins corresponding to apoB28 or larger were rapidly and efficiently secreted, whereas apoB18 and apoB23 were secreted much more slowly. These data imply that the size of these truncated apoB forms governs the lipid content of the apoB-containing lipoproteins formed as well as the kinetics of secretion.

Animals↗
PubMed1991

Investigating genomic imprinting and susceptibility to insulin-dependent diabetes mellitus: an epidemiologic approach.

Children of fathers with insulin-dependent diabetes mellitus (IDDM) are at greater risk of developing the disease than are children of IDDM mothers, reasons for which are currently unknown. To explore the possibility that genomic imprinting contributes to this phenomenon, 1,774 families with at least one IDDM child diagnosed before the age of 17 years and between 1950 and 1981 from the Children's Hospital at Pittsburgh IDDM Registry were evaluated. Approximately 1% of the mothers and 2.9% of the fathers were reported to have IDDM diagnosed before the age of 36 years (P less than 0.001). Excluding IDDM probands, the IDDM recurrence risk to siblings in families with an IDDM father was greater than that in families with an IDDM mother or in those with neither parent affected. Lifetable analyses revealed that among all children of diabetic fathers (probands included), there was a greater prevalence of IDDM, through age 30 years, for sons compared to daughters (59.5% vs. 34.1%, P = 0.02). However, there was no significant sex difference in the prevalence of IDDM among children of affected mothers (41.1% vs. 45.5%, P greater than 0.05). These data are not consistent with the genomic imprinting hypothesis and suggest that other genetic and/or environmental factors contribute to the increased risk for children of IDDM fathers.

Adolescent↗
PubMed1991

Comparative analysis of sequences at the 5' end of the human and mouse apolipoprotein B genes.

A comparison was made between the DNA sequences in two regions of the mouse and the human apolipoprotein B genes: the 5'-flanking sequence and the region between the first exon and the second intron. Considerable homology was observed, particularly in the immediate 5' region and in the second intron. Because promoter and enhancer elements have been previously localized to these regions in the human apolipoprotein B gene, it is proposed that regions of conserved base sequence delineate binding regions for regulatory proteins. In some cases, contiguous regions of homology are longer than expected for regions designed as recognition sites for individual nuclear proteins, and may define regions recognizable by a cluster of interacting proteins. Both the human and mouse genes contain repetitive elements and a hypervariable dinucleotide repeat.

Animals↗
PubMed1991

Another look at the black-white gap in gestation-specific perinatal mortality.

In the US, black infants born near or at term experience higher mortality than white infants. To extend our understanding of black-white differences in the relative advantages of growth (measured by birthweight) for gestational age, we compared race-specific rates of perinatal mortality by deviation in grams from the median birthweight for four categories of gestation (35-36, 37-38, 39-41, and 42-43 weeks). We also used race-specific standards to examine the difference between the median birthweight and the optimum birthweight (i.e. birthweight with the lowest mortality). The data, which were derived from vital records for singletons delivered in the US from 1983-1984, comprised 24,626 fetal and neonatal deaths among 5,157,197 white infants and 5973 fetal and neonatal deaths among 926,678 black infants. At all deviations from the median birthweight, black infants had relatively better survival at 35-36 weeks of gestation. This advantage was reversed among infants with gestations of 39-41 and 42-43 weeks. The optimum birthweight for black infants with gestations greater than or equal to 37 weeks was closer to their median birthweight than was that for white infants. For black infants with gestations of 39-41 weeks, the optimum birthweight was 187g (95% confidence interval (CI): 150-234) greater than the median birthweight (3289g); for comparable white infants the optimum birthweight was 397g (95% CI: 366-431) greater than the median birthweight (3487g). To reduce the black-white gap in perinatal mortality, we need a better understanding of aetiological relations between gestation, growth, and mortality.

Birth Weight↗
PubMed1991

Familial defective apo B-100, characterization of an Italian family.

Familial defective apolipoprotein (apo) B-100 is a genetic disorder presenting with hypercholesterolaemia and abnormal low-density lipoprotein (LDL) that binds poorly to LDL receptors. This disease appears to be caused by a mutation in the apo B-100 gene. In the present study thirteen members of a family with moderate hypercholesterolaemia (250-350 mg dl-1) were investigated. Biochemical studies on cultured skin fibroblasts ruled out classical familial hypercholesterolaemia (FH, receptor deficiency). We then studied the interaction between LDL and their receptors by an in vitro cell binding assay. LDL from nine affected members displayed a reduced affinity (2.5-fold) for the receptor, and were less effective than LDL from control and unaffected members in suppressing LDL receptor expression and in stimulating cholesterol esterification. LDL from the affected members had normal electrophoretic mobility, size and chemical composition. Partial delipidation did not modify the LDL binding defect. The disorder is transmitted over three generations as an autosomal codominant trait and all the affected members are heterozygotes and hypercholesterolaemics. Analysis of DNA from family members showed a point mutation leading to an Arg to Gln substitution at amino acid 3500 of the mature protein that segregated with hypercholesterolaemia and LDL defective binding. We conclude that this family is affected by familial defective apolipoprotein B-100 (FDB).

Adolescent↗
PubMed1991

Analysis of two different tandem repetitive elements within the human apolipoprotein B gene.

A large number of copies of the sequence (dTG-dAC)n, where n is between 10 and 60, exist in the human genome, and many are useful as polymorphic markers. One of these sequences occurs about 3 kilobases 5' of the human apolipoprotein (apo) B gene as seven distinguishable alleles containing from (TG)12 to (TG)18. This repeat is also present in the DNA of other primates. A second alternating purine-pyrimidine sequence with nine dinucleotide repeats and located in intron 4 is not polymorphic. Together with the apoB hypervariable repeat immediately 3' of the gene, the (TG)n sequence will provide a useful haplotype marker capable of distinguishing a large number of human apoB alleles, some of which may be associated with disease states.

Animals↗
PubMed1991

A polymorphism in a region with enhancer activity in the second intron of the human apolipoprotein B gene.

A 443-base pair fragment (+622 to +1064) from the second intron of the human apolipoprotein B gene was shown to contain a tissue-specific enhancer when placed in front of an apolipoprotein B promoter-chloramphenicol acetyltransferase construct in transfection experiments. To identify potential regulatory mutations in this region of the gene, DNA from various subjects was examined for the presence of point mutations by means of chemical cleavage of mismatched heteroduplexes. An A----G substitution within the second intron of the gene at position +722 was identified in three unrelated subjects and confirmed by DNA sequencing. Although the base substitution was contained within a nuclear protein-binding site, as determined by DNase I footprinting, it did not appear to affect the protein/DNA interaction in its vicinity, as shown by gel retardation experiments. The single base substitution at position +722 abolishes a StyI restriction site, thus creating a StyI polymorphism. Using allele-specific oligonucleotides, we screened the DNA of 172 subjects for the presence of this polymorphism: two other subjects carrying the polymorphism were found. In each of the five unrelated subjects, the polymorphism was associated with the same haplotype.

Apolipoproteins B↗