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B J McCarthy

Publications and source records attributed to B J McCarthy.

At least 73 records · Page 4Linked to original sources

Structure and expression of the Drosophila calmodulin gene.

We have isolated and characterized cDNA and genomic clones representing the calmodulin gene of Drosophila melanogaster. As demonstrated by genomic blots and by reconstruction experiments, the calmodulin gene is represented once in the Drosophila genome. In situ hybridization of cloned probes to the polytene chromosomes of third instar larvae permitted the localization of the gene to region 49A on the left arm of the second chromosome. Two transcripts of 1.65 and 1.9 kb are produced from this gene. The accumulation of calmodulin message was measured at several stages of Drosophila development. The results of these experiments suggest developmental regulation of the gene. Three intervening sequences interrupt the protein coding nucleotides and two of these are located within calmodulin functional domains. The DNA sequence encoding the protein is presented; the derived amino acid sequence is compared to that of other species. The structural similarities of the Drosophila calmodulin gene to calmodulin genes of other species and to other calcium binding protein genes are discussed.

Amino Acid Sequence↗

DNA sequence of the human apolipoprotein B gene.

The sequence of the human apolipoprotein B gene comprises 43 kb divided into 29 exons, one of which is unusually long and contains 7572 bp. Comparison of the gene sequence with four complete and three partial cDNA sequences published elsewhere reveals a total of 60 nucleotide substitutions and 39 amino acid substitutions and one small deletion in the signal peptide.

Amino Acid Sequence↗

Infant mortality in a rural health district in Georgia, 1974 to 1981.

In 1979 the infant mortality rate (IMR) dropped nearly 50% in a rural health district in southeast Georgia, and this lower rate continued during the next two years. For infants born during 1979 to 1981, the IMR was 12.4 as compared with 21.6 for those born from 1974 to 1978. Using linked birth and infant death records to identify shifts in the components of infant mortality in this district, we found that the change in IMR primarily reflected a decrease in neonatal and postneonatal deaths among infants with birth weight greater than or equal to 2,500 gm, rather than a change in the distribution of birth weights. Although the IMR was approximately twofold higher in white than in black infants, a similar relative decline in mortality was observed in both racial groups. For infants weighing greater than or equal to 2,500 gm, approximately half of the lower death rate was due to fewer deaths caused by infections. The decline in mortality in this district was greater than declines in neighboring districts and accompanied efforts to improve services for medically indigent mothers and infants. The findings suggest that in areas with high infant mortality, initial efforts to lower mortality should focus on primary care programs rather than more specialized interventions.

Black or African American↗

Factors affecting the sex differential in neonatal mortality: the role of respiratory distress syndrome.

We investigated factors affecting the sex differential in neonatal mortality rate using linked birth and death certificates of more than 300,000 infants born in Georgia between 1974 and 1977. The neonatal mortality rate was higher in male infants than in female infants (relative risk = 1.23, p less than 10(-8)) and was most pronounced for infants weighing between 1501 and 2500 gm (relative risk = 1.78, p less than 10(-8)). This differential persisted after adjustment was made for effects of several prenatal and labor-related factors. The male excess in neonatal mortality rate was most prominent during the first week of life and was found for several perinatal disorders. Respiratory distress syndrome-related mortality showed the largest male excess (relative risk = 1.57, p less than 10(-8)) and was most pronounced in infants weighing between 1501 and 2500 gm (relative risk = 2.78, p less than 10(-8)), in whom it accounted for roughly 60% of the excess. Since previous studies have shown that male infants have a higher incidence of respiratory distress syndrome but not a higher case-fatality rate, we suggest that slower lung maturation among male fetuses is a major contributing factor to the sex differential in neonatal mortality.

Birth Certificates↗

Regulation of Drosophila alpha- and beta-tubulin genes during development.

Both the alpha and the beta subunit of tubulin in Drosophila melanogaster are encoded by small multigene families. Using heterologous hybridization probes representing chicken alpha- and beta-tubulin genes, four complementary alpha- and four beta-tubulin gene sequences from Drosophila have been isolated. Each gene has been individually mapped cytogenically by in situ hybridization of nucleic acid probes to polytene chromosomes. It is clear that the genes in each family are dispersed rather than arranged in tandem arrays or clusters. Furthermore, alpha- and beta-tubulin genes are not physically linked as alpha-beta pairs. Transcripts from individual genes are differentially accumulated at particular stages of Drosophila development. This differential gene activity may provide expression of functionally specialized tubulin subunits. Alternatively, differences in expression may reflect tissue specific patterns of gene utilization.

Animals↗

Cesarean section. Risk and benefits for mother and fetus.

We studied the effects of cesarean section on neonatal mortality for breech infants and low--birth weight vertex infants using data from the Georgia neonatal surveillance network on 392,241 singleton deliveries between 1974 and 1978. The risk of neonatal death for breech infants weighing 4,000 g or less delivered vaginally was significantly higher than the risk for those delivered by cesarean section. The lower the birth weight, the higher the risk for a vaginal breech delivery. For breech infants weighing 1,000 to 2,500 g, the risk was almost 21/2 times greater for a vaginal delivery v a cesarean delivery. The best outcome for high-risk vertex infants weighing 1,000 to 1,500 g was for those delivered by cesarean section in a tertiary perinatal center. An increase in the cesarean section rate may be associated with increased neonatal survival; however, the benefits must be weighed against the costs of an increased maternal mortality and morbidity.

Birth Weight↗

In vitro transcription of Drosophila actin and 70,000-dalton heat shock protein genes.

Drosophila genomic DNAs containing a chromosomal locus 87C1 70,000-dalton heat shock protein gene, the locus 79B actin gene, and the 88F actin gene have been used as templates in an in vitro HeLa transcription system. RNA polymerase II-dependent transcription initiates from specific sites on the heat shock protein gene and the 79B actin gene. The locations of the transcription start sites were determined by two types of experiments: sizing of RNA runoff transcripts and S1 nuclease mapping of the 5' terminus of the in vitro transcripts. Transcription initiates at or near the in vivo initiation site of the heat shock protein gene and initiates at or near a site 14 nucleotides downstream of the in vivo start site of the 79B actin gene. The addition of the 79B actin, 88F actin, or heat shock protein templates to a HeLa extract transcription reaction precluded the transcription of a second template subsequently added. The exclusion occurs rapidly, within 15 s, is not dependent on transcription, and is only partially resistant to high concentrations of the second added template. We propose that stable protein-promoter complexes play an important role in maintaining exclusive transcription of the first template added in vitro.

Actins↗

The impact of publicly funded perinatal care programs on neonatal outcome, Georgia, 1976-1978.

The State of Georgia administers three publicly funded perinatal care programs for medically high risk and/or low-income women: the High Risk Pregnancy Program, the Medicaid Program, and the Maternal and Infant Care Projects. To assess the impact of these programs on infant health, we compared the birth weight distribution and neonatal mortality rates of infants born to women in each program with those of infants of a nonfunded group of women with less than 12 years' education. Infants of women in publicly funded groups were more likely to weigh less than or equal to 2,500 gm at birth than those of women in the nonfunded group. Neonatal mortality rates for publicly funded groups were similar to those of the nonfunded group. The neonatal mortality rates for infants of birth weight less than or equal to 2,500 gm of publicly-funded women were significantly lower than those of the nonfunded women. There were no significant differences between groups for neonatal mortality rates for infants of birth weight greater than 2,500 gm. These findings suggest that publicly funded perinatal care programs may improve neonatal survival of infants of birth weight less than or equal to 2,500 gm of low-income mothers.

Adult↗

Isoprene synthesis in isolated embryonic Drosophila cells. I. Sterol-deficient eukaryotic cells.

Since insects are cholesterol auxotrophs, we analyzed the apparent paradox presented by an established cell line (Kc cells) from Drosophila embryos which grew in media which contained less than 0.05 micrograms/ml of sterols. Fresh Drosophila embryos contained 3.7 micrograms of 3 beta-hydroxysterols/mg of protein; however, Kc cells had maximally 0.50 micrograms of 3 beta-hydroxysterols/mg of protein. Kc cells, grown in media which contained cholesterol, showed the presence of sterol in their plasma and intracellular membranes. Kc cells did not synthesize sterols or any apparent replacement lipophilic molecule. However, two major compounds which comigrated with ubiquinone and dolichol were synthesized from radioactive mevalonate and acetate. Cholesterol incorporation into Kc cell membranes did not significantly alter total phospholipid head or acyl group composition. Similar observations were obtained with Schneider's Drosophila cell line I and a mosquito (Aedes albopictus) cell line. Our results (a) challenged current concepts that sterols or related replacement isopentenoid molecules were required for eukaryotic membrane structure, (b) demonstrated that marked alterations in eukaryotic membrane sterol composition was insufficient to change total phospholipid head and/or acyl group composition, and (c) set the stage for the use of a eukaryotic cell to examine the regulation of 3-hydroxy,3-methylglutaryl coenzyme A reductase activity independent of a requirement for sterol synthesis.

Animals↗

Two Drosophila actin genes in detail. Gene structure, protein structure and transcription during development.

DNA fragments representing the six Drosophila actin genes have been isolated by recombinant DNA techniques. We have compared the transcriptional characteristics of the actin genes at the cytological loci 79B and 88F. The activity of each gene in vivo was examined using gene-specific probes from transcribed, but non-translated 3' regions of each gene. The genes show similar patterns of transcriptional activity during development until the pupal stage, with two periods showing RNA accumulation at two to three hours and 12 to 15 hours during embryonic development, followed by large increases in the proportion of message from each gene in first and second instar larvae. During pupal development, the 88F gene apparently produces a larger proportion of transcripts than at any other developmental stage, while the transcripts of the 79B gene are reduced to a level lower than in first and second instar larvae. The 5' end of each messenger RNA in larvae has been mapped by nuclease S1 digestion of hybrids between restriction fragments of genes and homologous mRNAs. The two genes display widely differing capacities to serve as templates for transcription in vitro in HeLa cell extracts. The complete DNA sequences of both genes including the flanking regions immediately 3' and 5' to the gene are presented. These data permit comparison of the DNA sequences of these Drosophila actin genes with each other and with the DNA sequence and protein sequence information available for the actins of Drosophila and other organisms. These two genes share the common structural feature of an intervening sequence at amino acid 307, though the sequences within each intron differ greatly. This may be a reflection of a duplication event, followed by divergence of the intervening sequences. We discuss possible correlations between the DNA sequences of each 5' flanking region and the differences in transcriptional characteristics of these two distinct but closely related genes.

Actins↗

Neonatal transport in Georgia: implications for maternal transport in high-risk pregnancies.

We analyzed population-based data from the Georgia Neonatal Surveillance Network from 1974 to 1978 to determine the effect of the hospital of delivery on the neonatal mortality rate (NMR) of infants later admitted to neonatal intensive case units (NICUs). The NMR of 3,524 infants transported from primary centers to NICUs was significantly higher [relative risk (RR) = 2.1; 95% CL = 1.9 to 2.3] than that of 10,764 infants born in tertiary centers and admitted directly to an NICU. This effect persisted even after adjustment for birth-weight differences (RR = 1.6; 95% CL = 1.5 to 1.8). The relative risk in favor of delivery in a tertiary center increased with increasing birth weight. However, the proportion of infants of less than 1,000 gm surviving was higher for transported infants and increased with distance transported. This finding suggests that, at these very low birth weights, the hardiest infants were selectively transported. A surprising finding was the very low proportion of low-birth-weight infants delivered in primary centers and transported to NICUs (eg, 32% of infants weighing between 1,001 and 1,200 gm). Our findings support previous reports that delivery in a hospital with an NICU is preferable to later neonatal transport and suggest that efforts to increase the rate of maternal transport in high-risk pregnancies can lead to a substantial reduction in infant deaths.

Adolescent↗

Identifying neonatal risk factors and predicting neonatal deaths in Georgia.

A predictive model which identifies 38% of the neonatal deaths by isolating only 11% of the births was formulated. It utilized existing vital records data for 230,585 single live births which occurred in Georgia for the period 1974-1976, to describe factors recorded on the birth certificate which are determinants of neonatal mortality on a statewide basis. Maternal age, race, premature birth, spontaneous abortion or stillbirth, complications related to pregnancy, complications not related to pregnancy, and type of birth (multiple gestation) were found to be statistically significant. It is proposed that private physicians evaluate patients on the basis of this model to facilitate estimates of risk of a neonatal death. In addition, public health physicians could utilize this model to make informed decisions in regard to the management of public health programs directed at the care of pregnant women.

Female↗

Age at onset of necrotizing enterocolitis. Risk factors in small infants.

We compared the features of 45 infants with early-onset necrotizing enterocolitis (NEC) (in the first ten days of life) and 41 infants with late-onset NEC (after the tenth day of life); all weighed 1,500 g or less at birth. Infants with late-onset NEC were smaller at birth and had younger gestational ages than infants with early-onset illness. No significant differences between the two groups, however, were found in sex or race distribution, mean one- and five-minute Apgar scores, or in the relative frequency of occurrence of 30 maternal and neonatal risk factors. Intravenous alimentation was administered significantly more frequently to infants with late-onset NEC. Birth weight-specific weekly attack rates for NEC declined dramatically when infants reached the equivalent of 35 to 36 weeks' gestational age. We hypothesize that the timing of noxious events in relation to gut maturity may explain these observations.

Age Factors↗

Expression and novel structure of a collagen gene in Drosophila.

We report the structure and developmental expression of collagen gene sequences in Drosophila melanogaster. Collagen-like genomic clones were isolated by screening a Drosophila genomic library with a chicken pro alpha 2(I) cDNA clone as a hybridization probe. A 1.5-kilobase (kb) DNA sequence from a 9.2-kb DNA clone (pDCg1) is presented. Unlike the highly fragmented genes for vertebrate type I collagen, there is no evidence of a 54-base-pair primordial unit within this gene segment. Instead, the fragment is composed of two large coding sequences. Together they specify a sequence of 469 amino acids. This collagen product is composed almost entirely of the Gly-X-Y repeat characteristic of peptides involved in triple helix formation. Within the polypeptide there are four minor discontinuities in the Gly-X-Y pattern. Similar interruptions have been observed in a mouse basement membrane collagen protein sequence. Therefore, the Drosophila collagen gene may encode a nonfibrous collagen such as a basement membrane or cuticle collagen or a novel collagenous protein. By using the DNA segment of known sequence as a hybridization probe, a developmental sequence of polyadenylylated RNA samples was screened for the presence of homologous sequences. A RNA species 6.4 kb in length was detected as a prominent band only in the first- and second-instar larval stages. This pattern of developmental hybridization correlates with the production of the cuticle and basement membranes, and the large size of the RNA is consistent with its identification as a collagen-encoding RNA.

Animals↗