EcoT14I RFLP found at the human amyloid beta protein gene locus.
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Amyloid↗
Biomedical subjects
B Cordell
Publications and source records attributed to B Cordell.
Selective reduction of mRNA for the beta-amyloid precursor protein that lacks a Kunitz-type protease inhibitor motif in cortex from Alzheimer brains.
In poly(A) RNA from cerebral cortex obtained postmortem from victims of Alzheimer's disease (AD), an alternatively spliced mRNA for the amyloid precursor protein (APP-695 mRNA) was shown to be decreased by 65%. Another form (APP-751 mRNA) with an additional exon encoding a Kunitz-type (serine) protease inhibitor motif did not change appreciably (less than 30% decrease) in AD cortex. If this twofold increase in the APP-751 mRNA/APP-695 mRNA ratio results in a corresponding increase in the APP-751/APP-695 protein ratio, this would support the hypothesis that impaired proteolysis promotes the accumulation of abnormal proteins in the brain during AD. In the two previously known, major alternatively spliced forms of ca. 3.3 and 3.5 kb, we resolved doublet RNAs for each form that are consistent with sequence data showing multiple polyadenylation sites (J. Kang et al., 1987, Nature (London) 325, 733-736.). Smaller APP-related transcripts were also found (1.1, 1.0, 0.8, and 0.3 kb), some of which are selectively altered in AD.
Alzheimer Disease↗
Accumulation of abundant messenger ribonucleic acids during postnatal development of mouse small intestine.
To describe the differentiation of the small bowel at the molecular level, intestinal messenger ribonucleic acids (mRNAs) from mice at different stages of fetal and postnatal development were investigated. On the basis of cell-free translation and complementary deoxyribonucleic acid cloning experiments, abundant mRNAs coding for small polypeptides of 6-12 kilodaltons (low-molecular-weight mRNAs) were found in adult small intestine but not in the fetal gut. These developmentally regulated low-molecular-weight mRNAs are uniquely abundant in jejunum and ileum of adult mice, but they are absent or occur only at low levels in the duodenum, colon, stomach, and all other mouse organs examined. Low-molecular-weight mRNAs begin accumulating in the small bowel at approximately 3 wk of age, coinciding with weaning and with profound changes in intestinal differentiation. One complementary deoxyribonucleic acid clone of a low-molecular-weight mRNA (asb4/134) is specific to the distal small bowel, specifically accumulates at weaning, and hybridizes to RNA from mouse testis and brain at approximately 2%-5% of the intestinal level. Low-molecular-weight mRNA sequences may provide important markers of intestinal differentiation at the genetic level, leading to a better understanding of the factors that contribute to its postnatal maturation.
Animals↗
Growth hormone regulates expression of rat liver cytochrome P-450 15 beta at a pretranslational level.
Polyclonal antibodies to rat liver microsomal cytochrome P-450 15 beta-hydroxylase were used to screen a female rat liver cDNA expression library. Recombinant plasmid C-6, isolated from a positive colony, contained a cDNA of 1000 base pairs which hybridized to a single, 1.7 kilobase class of mRNA on Northern blot analysis. Semi-quantitative slot blots showed that the level of this mRNA was 17-fold lower in male rat liver than in females. Continuous infusion of human growth hormone to male rats caused them to express female levels of C-6 mRNA, while the same daily dose of hormone given intermittently had no effect. A high degree of correlation of the levels of C-6 mRNA with 15 beta-hydroxylase protein levels and catalytic activities was found, demonstrating that the sexually differentiated, growth hormone-dependent expression of the 15 beta-hydroxylase is regulated at a step preceding translation.
Animals↗
Purification and subunit composition of atrial natriuretic peptide receptor.
A receptor for atrial natriuretic peptide (ANP) was purified 2700-fold, to apparent homogeneity, from cultured bovine aortic smooth muscle cells by affinity chromatography. The native ANP receptor has a molecular weight of 125,000 as determined by both metrizamide gradient centrifugation and nonreducing NaDodSO4/polyacrylamide gel electrophoresis. With 125I-labeled ANP as ligand, the purified receptor bound a maximum of 5.70 nmol of ligand per mg of protein and the dissociation constant was 4.0 X 10(-10)M. Upon treatment with 10 mM dithiothreitol, the purified receptor migrated as a single band at Mr 60,500 in NaDodSO4/polyacrylamide gel electrophoresis. These findings show that the holoreceptor for ANP in vascular tissue is composed of two subunits of identical apparent molecular weight, presumably linked by a disulfide bridge(s).
Animals↗
Nucleotide and deduced amino acid sequence of the influenza neuraminidase genes of two equine serotypes.
Equine influenza is caused by two serotypes of type A influenza virus, EIV-A1 and EIV-A2. The complete nucleotide sequence of the neuraminidase (NA) genes of both the A1 (N7 subtype) and A2 (N8 subtype) serotype has been determined following cloning of full-length viral NA cDNAs into pBR322. Analysis of the deduced amino acid sequences reveals that the N7 and N8 genes share expected extensive homologies with the previously sequenced N1, N2, and N9 NA subtypes. These homologies include conservation of basic NA gene and protein structure, cysteine residues, potential glycosylation sites, and residues known to reside in the enzyme active site of the NA molecule. Additionally, the N1 and N8 molecules and the N7 and N9 molecules are more related by total amino acid homology than any other combination of two subtypes. The area of homology in both cases is particularly strong in the region of residues 100-205, an area roughly corresponding to the amino terminal one-third of the "head" of the NA protein.
Amino Acid Sequence↗
Regulation of pulmonary surfactant apoprotein SP 28-36 gene in fetal human lung.
Pulmonary surfactant stabilizes lung alveoli, preventing respiratory failure and hyaline membrane disease in premature infants. In addition to lipids, surfactant contains apoproteins that are thought to be critical for normal surfactant function. We have examined the ontogeny and regulation of the major surfactant-associated protein of molecular mass 28-36 kDa (SP 28-36) in human fetal lung. SP 28-36 was not detected in tissue from second trimester abortuses by either immunoblot analysis or enzyme-linked immunosorbent assay (less than 0.02 microgram per mg of DNA). Levels of mRNA for SP 28-36, assayed by cDNA hybridization, were low or undetectable in all preculture specimens. The concentration of saturated phosphatidylcholine in lung tissue was 30% of the adult value with no apparent increase between 15 and 24 weeks gestation. SP 28-36 content increased during explant culture in the absence of serum and hormones, exceeding adult levels (3.2 +/- 1.0 micrograms per mg of DNA) after 5 days. In cultures treated with triiodothyronine (2 nM) and dexamethasone (10 nM), hormones that regulate phosphatidylcholine synthesis, the increase in SP 28-36 was accelerated (treated/control ratio was 7.1 and 3.4 at 3 and 5 days, respectively). Levels of mRNA for SP 28-36 also increased during culture and were stimulated by hormones (treated/control = 8.6 and 1.9 at 3 and 5 days, respectively). SP 28-36 and its mRNA increased similarly in the presence of dexamethasone alone, whereas triiodothyronine alone had no apparent effect. The molecular weight and charge pattern was similar for SP 28-36 of adult and cultured fetal tissue. These findings indicate that expression of the SP 28-36 gene is low during the second trimester, increases during explant culture, and is accelerated by glucocorticoid treatment.
Apoproteins↗
Detection of insulin synthesis in mammalian anterior pituitary cells by immunohistochemistry and demonstration of insulin-related transcripts by in situ RNA-DNA hybridization.
Insulin or highly homologous transcripts is shown to be synthesized in cultures of mammalian anterior pituitary cells using cloned insulin-specific cDNA probes and nucleic acid cytochemistry. The insulin-hybridizing cells are less abundant than the growth hormone-producing cells, occurring in the cultures at approximately one tenth the frequency. Immunocytochemistry demonstrates that insulin or insulin-like proteins is also synthesized by the cultured pituitary cells and that the insulin immunoreactivity is contained within secretory granules. It appears that many of these secretory granules are concentrated around the periphery of the cell, unlike the insulin-containing granules in pancreatic B-cells.
Animals↗
Structure of canine pulmonary surfactant apoprotein: cDNA and complete amino acid sequence.
The apoproteins of pulmonary surfactant (PSAP) are thought to be critical for normal surfactant function. They bind to surfactant phospholipids and enhance their ability to form surface films in vitro. These acidic glycoproteins have monomeric molecular weights of 36,000, 32,000, and 28,000 (PSAP-36, -32, and -28). Each member of this family of proteins has a similar amino acid composition and their differences in electrophoretic mobility are due in part to glycosylation. We have derived the full amino acid sequence of PSAP-32 from the nucleotide sequence of PSAP cDNA. A cDNA library was prepared from canine lung poly(A)+ RNA and screened with oligonucleotide probes that were based on the NH2-terminal amino acids of PSAP-32 determined by Edman degradation. This protein has the striking feature of collagen-like and non-collagen-like sequences in the same polypeptide chain. There are 24 Gly-Xaa-Yaa triplets, where Yaa is often hydroxyproline. These repeats comprise one-third of PSAP near the NH2 terminus. The remaining two-thirds of PSAP is resistant to bacterial collagenase digestion and contains a possible N-glycosylation site near the carboxyl terminus. The NH2-terminal one-third of PSAP-32 probably contains the cysteine involved in interchain disulfide bonds.
Amino Acid Sequence↗
Patient education evaluation: beyond intuition.
Intuitive ideas about problem areas gleaned from the literature as well as practice settings can provide nurses with a multitude of patient education evaluation issues. The nurse who is interested in evaluating patient education should review existing studies in the literature, sampling both process and outcome. Thoughtful planning and implementation of a patient education study can be personally satisfying. In addition, such an undertaking will contribute to the body of knowledge in patient education and provide valuable information to other patient educators. It is natural that nurses should pursue the rewards of patient education evaluation for themselves and their patients.
Evaluation Studies as Topic↗
Polymorphism in the 5' flanking region of the human insulin gene: a genetic marker for non-insulin-dependent diabetes.
We sought to determine whether differences in the human insulin gene or its immediate flanking sequences could be found in diabetes. Peripheral leukocyte DNA from 217 unrelated persons, including blacks, whites, and Pima Indians, was analyzed by restriction-enzyme digestion, blotting to nitrocellulose filters, and hybridization to cloned [32P]insulin-gene probes. A region of length variation including deletions (0.1 to 0.2 kilobase pairs) or insertions (0.6 to 5.5 kb) of DNA was found only in the immediate 5' flanking region in 33 per cent of the genes examined. A 1.6-kb insertion accounted for 80 per cent of the polymorphism. This variant was found more often in subjects with non-insulin-dependent diabetes than in nondiabetics, regardless of race (P = 0.011). Length polymorphism in the 5' flanking region of the insulin gene may provide a genetic marker for non-insulin-dependent diabetes.
Adolescent↗
Recombination within and between the human insulin and beta-globin gene loci.
We detected a large number of polymorphic insulin restriction fragments in black Americans. These different size fragments were probably generated by unequal recombination on both sides of the human insulin gene. Population genetic analysis indicates that recombination occurred 33 times more frequently than expected to generate this large number of polymorphic fragments. Specific properties of the unique repeated 14- to 16-base-pair sequences 5' to the insulin gene suggest that this sequence would promote increased unequal recombination. Additional pedigree analysis showed that the recombination rate between the structural insulin and beta-globin gene loci was 14% with strong evidence for linkage. Since both insulin and beta-globin have been mapped to the short arm of human chromosome 11, this study establishes that the genetic map distance between these genes is 14.2 centimorgans.
Base Composition↗
Assigning the polymorphic human insulin gene to the short arm of chromosome 11 by chromosome sorting.
We have determined the subchromosomal location of the human insulin gene by analyzing DNA isolated from sorted human metaphase chromosomes. Metaphase chromosome suspensions were sorted into fractions according to relative Hoechst fluorescence intensity by the fluorescence activated chromosome sorter. The chromosomal DNA in each fraction was characterized by restriction endonuclease analysis. Initial sorts indicated that the insulin gene-containing fragment resided in a fraction containing chromosomes 9, 10, 11, and 12. Studies of cell lines that contained chromosome translocations permitted the assignment of the insulin gene to a derivative chromosome that contains portions of the short arm of chromosome II. Simultaneous sorting of the normal homolog from this small derivative chromosome separated the two different sized insulin gene-containing restriction fragments in this individual. These data indicate that the two restriction fragments represent insulin gene polymorphism and not duplicate gene loci.
Alleles↗
Disproportionate expression of the two nonallelic rat insulin genes in a pancreatic tumor is due to translational control.
The expression of the two nonallelic but highly homologous rat insulin genes (1 and 2) in a transplantable beta-cell tumor is found to be 10-fold higher for rat1 insulin than rat2 insulin, while in normal pancreatic tissue there are approximately equal amounts of each protein. No large sequence rearrangements of the genes were apparent by restriction analysis of the tumor DNA, and both genes were found to be specifically hypomethylated in the tumor as compared with other nonpancreatic tissue. Equivalent amounts of both insulin 1 and 2 precursor transcripts, as well as stable, mature mRNAs were detected in the tumor. However, two-dimensional gel analysis of immunoprecipitated rat1 and rat2 preproinsulins synthesized in vitro revealed a 10:1 ratio of rat1 to rat2 proteins. A 1:1 ratio was obtained when the tumor mRNA was treated in vitro with vaccinia virus capping extract, suggesting a structural modification at the 5' terminus of the rat2 mRNA. These results are discussed in the context of insulin regulation by glucose, shown to be due to translational control.
Adenoma, Islet Cell↗
Polymorphism in the 5'-flanking region of the human insulin gene and its possible relation to type 2 diabetes.
The arrangement of the human insulin gene in DNA from 87 individuals was analyzed by the Southern blot hybridization technique with a cloned genomic human insulin probe. Insertions of 1.5 to 3.4 kilobase pairs in the 5'-flanking region of the gene were found in DNA from 38 individuals. These insertions occurred within 1.3 kilobase pairs of the transcription initiation site. In contrast, no insertions were observed in the region 3' to the coding sequence. The prevalence of these insertions in type 2 diabetes was significantly greater than in the other groups (P less than .001). The limitation of this striking length polymorphism to a potential promoter region suggests that these insertions may play a role in insulin gene expression.
Base Sequence↗
The forms of tRNATrp found in avian sarcoma virus and uninfected chicken cells have structural identity but functional distinctions.
We have determined the complete nucleotide sequence of the avian tRNATrp which serves as primer for avian retrovirus DNA synthesis by the viral polymerase. The sequence is identical to that reported for tRNATrp present in uninfected avian cells (Harada, F., Sawyer, R. C., and Dahlberg, J. E. (1975) J. Biol. Chem. 250, 3487-3497). Although there appears to be only a single species of tRNATrp in avian cells, two functionally different forms within the population can be distinguished. We show that the tRNATrp isolated from virions can act in vitro as an efficient suppressor for UGA. The suppressor activity is roughly 3-fold greater with viral tRNATrp than with cellular tRNATrp. In addition, it has been reported (Panet, A., Haseltine, W. A., Baltimore, D., Peters, G., Harada, F., and Dahlberg, J. E. (1975) Proc. Natl. Acad. Sci. U. S. A. 72, 2535-2539) that the viral polymerase can bind 100% of viral tRNATrp, but only 30% of cellular tRNATrp. Hence, avian retroviruses seem to selectively incorporate and utilize only one of these forms. Since the nucleotide sequence and nucleoside modifications are identical between viral and cellular tRNATrp, two conformations of avian tRNATrp may exist which can influence several biological activities of the molecule.
Alpharetrovirus↗
Sequence of the human insulin gene.
The human insulin gene contains two intervening sequences, one is within the region transcribed into the 5'-untranslated segment of the mRNA and the other interrupts the C-peptide encoding region. A comparison of the human with the rat insulin genes indicates potential regulatory regions in the DNA segment preceding the gene and suggests that the ancestral form of the insulin gene had two intervening sequences.
Alleles↗
Nucleotide sequence of a cDNA clone encoding human preproinsulin.
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Amino Acid Sequence↗