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Biomedical subjects

A C Wilson

Publications and source records attributed to A C Wilson.

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

Sex differences in the management and long-term outcome of acute myocardial infarction. A statewide study. MIDAS Study Group. Myocardial Infarction Data Acquisition System.

BACKGROUND: We wished to evaluate whether differences in the rate of invasive cardiac procedures between men and women with acute myocardial infarction are associated with different short- and long-term mortality. METHODS AND RESULTS: The database (Myocardial Infarction Data Acquisition System, MIDAS) included all discharges for the years 1986 and 1987 with the diagnosis of acute myocardial infarction in New Jersey, based on the New Jersey hospital discharge data system (MIDS/UB-82). Accuracy of the data was evaluated by auditing 726 randomly selected charts. The variables examined included age, sex, race, comorbidity (anemia, chronic liver disease, cancer, chronic obstructive pulmonary disease, diabetes, hypertension, prior myocardial infarction), complications (left ventricular dysfunction, arrhythmias, conduction defects), insurance status, performance of cardiac catheterization, percutaneous transluminal coronary angioplasty, or coronary artery bypass graft surgery, and survival up to 3 years. Women were older, had longer hospital stay, and were more likely than men to have anemia, diabetes, hypertension, left ventricular dysfunction, and Medicare or Medicaid insurance coverage. They were less likely than men to be admitted to a hospital equipped to perform invasive procedures or to have chronic obstructive pulmonary disease, chronic liver disease, prior myocardial infarction, or arrhythmias. After adjustment for these differences, women were less likely than men to have cardiac catheterization. Cardiac catheterization was associated with lower mortality. Women up to age 70 had higher 3-year death rates than men after adjustment for age, race, comorbidity, complications, and insurance type. This difference between men and women was somewhat diminished after the performance of cardiac catheterization and revascularization was taken into account. Unadjusted mortality was high in this study group. CONCLUSIONS: Women with acute myocardial infarction are less likely to have invasive cardiac procedures and have higher 3-year adjusted death rate up to age 70 than men.

Aged↗
PubMed1994

Nonpharmacologic therapy improves functional and emotional status in congestive heart failure.

PURPOSE: To compare the effects of a multimodal nonpharmacologic intervention to digoxin and to placebo in patients with congestive heart failure receiving background therapy with angiotensin-converting enzyme inhibitors. DESIGN: Randomized, parallel assignment to three treatment groups of 20 patients with congestive heart failure (New York Heart Association Class II and III). INTERVENTION: Nonpharmacologic treatment program included the following: (1) graduated exercise training, three to five times per week; (2) structured cognitive therapy and stress management; and (3) dietary intervention aimed at salt reduction and weight reduction in the overweight. Digoxin was titrated to achieve a blood level between 0.8 and 2.0 ng/ml. Placebo and digoxin were administered in a randomized, double-blind fashion. RESULTS: Echocardiographic ejection fraction improved (p < 0.05) in the digitalis group (change = +4.4 +/- 6.5) compared with both placebo (change = -3.2 +/- 3.9) and nonpharmacologic therapy (change = -3.2 +/- 3.9). The nonpharmacologic treatment program was well tolerated by all patients and resulted in significant improvement (p < 0.05) in exercise tolerance (digoxin = +51 +/- 50 s, placebo = +91 +/- 76, nonpharmacologic therapy = +182 +/- 139), as well as Beck Depression Inventory score (digoxin = +1.2 +/- 4.4, placebo = +2.0 +/- 4.2, nonpharmacologic therapy = -5.0 +/- 4.2), Hamilton Scale scores of anxiety (digoxin = +3.0 +/- 6.8, placebo = +6.0 +/- 2.6, nondrug therapy = -5.2 +/- 5.4), and depression (digoxin = +1.0 +/- 4.9, placebo = +5.0 +/- 5.0, nonpharmacologic therapy = -6.6 +/- 10.1). In addition, weight loss was significantly greater with nonpharmacologic therapy (digoxin = +0.32 +/- 1.76 kg; placebo = -1.35 +/- 1.44 kg; nonpharmacologic therapy = -4.37 +/- 4.50 kg) compared with both digoxin and placebo. CONCLUSIONS: Nonpharmacologic therapy improved functional capacity, body weight, and mood state in patients with congestive heart failure. In contrast, digoxin improved ejection fraction without corresponding changes in exercise tolerance or quality of life.

Aged↗
PubMed1993

DNA replication facilitates the action of transcriptional enhancers in transient expression assays.

We demonstrate a general role for DNA replication in the activation of gene transcription in transient transfection assays. The effect is observed for a wide range of genes and cell types, transfected by a number of protocols and is independent of increased template copy number. Replication does not stimulate transcription driven by proximal promoter elements alone but requires a functional enhancer element. This synergy between an active replication origin and an enhancer is not confined to elements from viruses such as SV40, which undergo an early to late switch in gene expression that is tightly coupled to replication, since the enhancer-containing long terminal repeats from retroviruses are strongly stimulated by replication. Furthermore, synthetic enhancers consisting of multimerised binding sites for one or two factors are also subject to replication-activation. The diversity of synthetic and natural enhancers used in this study suggests that replication and transcription do not share a common protein factor. We propose that replication leads to chromatin modifications that facilitate enhancer action.

Animals↗
PubMed1993

The VP16 accessory protein HCF is a family of polypeptides processed from a large precursor protein.

Upon lytic infection of permissive cells, the herpes simplex virus (HSV) transactivator protein VP16 associates with an accessory protein termed host cell factor (HCF). Binding to HCF activates VP16 for association with the octamer motif-binding protein Oct-1, to form a multiprotein-DNA complex responsible for activating transcription of the HSV immediate early genes. We show that HCF comprises a series of related polypeptides that range from 110 to 300 kd, all of which are encoded by a single gene. Although there is no obvious sequence similarity between HCF and other known proteins, HCF contains eight repeats of a new 26 amino acid motif. cDNAs encoding HCF predict a large open reading frame of 2035 codons. When expressed in human cells, this large open reading frame encodes both the 300 kd and smaller HCF polypeptides, indicating that the smaller polypeptides arise by processing of the 300 kd protein.

Amino Acid Sequence↗
PubMed1993

High-resolution mapping of the HyHEL-10 epitope of chicken lysozyme by site-directed mutagenesis.

The complex formed between hen egg white lysozyme (HEL) and the monoclonal antibody HyHEL-10 Fab fragment has an interface composed of van der Waals interactions, hydrogen bonds, and a single ion pair. The antibody overlaps part of the active site cleft. Putative critical residues within the epitope region of HEL, identified from the x-ray crystallographic structure of the complex, were replaced by site-directed mutagenesis to probe their relative importance in determining affinity of the antibody for HEL. Twenty single mutations of HEL at three contact residues (Arg-21HEL, Asp-101HEL, and Gly-102HEL) and at a partially buried residue (Asn-19HEL) in the epitope were made, and the effects on the free energies of dissociation were measured. A correlation between increased amino acid side-chain volume and reduced affinity for HELs with mutations at position 101 was observed. The D101GHEL mutant is bound to HyHEL-10 as tightly as wild-type enzyme, but the delta delta Gdissoc is increased by about 2.2 kcal (9.2 kJ)/mol for the larger residues in this position. HEL variants with lysine or histidine replacements for arginine at position 21 are bound 1.4-2.7 times more tightly than those with neutral or negatively charged amino acids in this position. These exhibit 1/40 the affinity for HyHEL-10 Fab compared with wild type. There is no side-chain volume correlation with delta delta Gdissoc at position 21. Although Gly-102HEL and Asn-19HEL are in the epitope, replacements at these positions have no effect on the affinity of HEL for the antibody.

Amino Acid Sequence↗
PubMed1993

Evolution of maize inferred from sequence diversity of an Adh2 gene segment from archaeological specimens.

A segment of the nuclear gene encoding alcohol dehydrogenase 2 (Adh2) was amplified and sequenced from extracts of archaeological maize specimens up to 4700 years old and from contemporary samples. Sequence diversity in ancient maize equals that of contemporary maize. Some ancient Adh2 alleles are identical or closely related to contemporary alleles. The data suggest that the gene pool of maize is millions of years old and that domestic races of maize stem from several wild ancestral populations.

Alcohol Dehydrogenase↗
PubMed1993

Evolution of rodent lysozymes: isolation and sequence of the rat lysozyme genes.

Mice have two lysozyme c genes that are the products of a gene duplication. The rat genome also possesses two lysozyme genes, which implies that the duplication of the lysozyme gene preceded the mouse-rat divergence. Concerted evolution has homogenized the 3' half (middle of exon 2 through 3' flanking) of the genes in each species. A mosaic pattern of concerted evolution is found for the 5' half of the gene, with both the 5' and 3' ends, but not the middle, of exon 1 evolving in a concerted fashion. Differences exist in the homogenization pattern in the rat and mouse, suggesting the existence of species-specific patterns of concerted evolution. Exon 1 contains most of the amino acid substitutions that distinguish mouse M from mouse P lysozyme or rat 1 from rat 2 lysozyme. Some of the amino acid differences found between mouse lysozyme genes are found also in the rat, and they suggest that rat 1 and 2 are homologous to mouse M and P, respectively. Nuclease S1 mapping indicated that only the rat 1 gene is expressed at detectable levels, and, specifically, that this gene is expressed by cells in the lung, small intestine, and spleen. The mouse expresses different lysozyme genes in the intestinal (P) and macrophage (M) cells, while the rat expresses only one gene in both of these tissues. The absence of detectable expression and the accumulation of a large number of amino acid substitutions in the parts of exons 1 and 2 of the rat 2 gene not participating in concerted evolution suggest that the rat 2 gene is a pseudogene.

Amino Acid Sequence↗
PubMed1993

Toward a more accurate time scale for the human mitochondrial DNA tree.

Several estimates of the time of occurrence of the most recent common mitochondrial DNA (mtDNA) ancestor of modern humans have been made. Estimates derived from noncoding regions based on a model that classifies sites into two categories (variable and invariable) have been consistently older than those derived from the third positions of codons. This discrepancy can be attributed to a violation of the assumption of rate homogeneity among variable sites when analyzing the noncoding regions. Additional data from the partial control region sequences allow us to take into account some of this further heterogeneity. By assigning the sites to three classes (highly variable, moderately variable, and invariable) and by assuming that the last common mtDNA ancestor of humans and chimpanzees lived 4 million years ago, the most recent common mtDNA ancestor of humans is estimated to have occurred 211,000 +/- 111,000 years ago (+/- 1 SE), consistent with the estimate, 101,000 +/- 52,000 years, made from third positions of codons and also with those proposed previously. We used the same technique to estimate when a putative expansion of modern humans out of Africa took place and estimated a time of 89,000 +/- 69,000 years ago. Even though the standard errors of these estimates are large, they allow us to reject the multiregional hypothesis of modern human origin.

Africa↗
PubMed1993

Characterization of the cow stomach lysozyme genes: repetitive DNA and concerted evolution.

Cow stomach lysozyme genes have evolved in a mosaic pattern. The majority of the intronic and flanking sequences show an amount of sequence difference consistent with divergent evolution since duplication of the genes 40-50 million years ago. In contrast, exons 1, 2, and 4 and immediately adjacent intronic sequences differ little between genes and show evidence of recent concerted evolution. Exon 3 appears to be evolving divergently. The three characterized genes vary from 5.6 to 7.9 kilobases in length. Different distributions of repetitive DNA are found in each gene, which accounts for the majority of length differences between genes. The different distributions of repetitive DNA in each gene suggest the repetitive elements were inserted into each gene after the duplications that give rise to these three genes and provide additional support for divergent evolution for the majority of each gene. The observation that intronic and flanking sequences are evolving divergently suggests that the concerted evolution events involved in homogenizing the coding regions of lysozyme genes involve only one exon at a time. This model of concerted evolution would allow the shuffling of exon-sized pieces of information between genes, a phenomenon that may have aided in the early adaptive evolution of stomach lysozyme.

Animals↗
PubMed1993

Pathways of lysozyme evolution inferred from the sequences of cytochrome b in birds.

A reliable phylogeny relating the major groups of Galliformes was sought in order to shed light on an unusual case of coupled amino acid replacements in the lysozymes c of these birds. The New World quail and the African guinea fowl share a unique trio of amino acids at three internal positions but have been separated phylogenetically by the majority of trees based on morphological characters. Alternative hypotheses based on molecular data have suggested an arrangement that would be more parsimonious with regard to the lysozyme data. The entire mitochondrial cytochrome b gene (1,143 bp) was amplified via the polymerase chain reaction (PCR) and sequenced for nine galliforms and a representative anseriform to provide DNA sequence data for a phylogenetic reconstruction. The mode and tempo of change in these sequences were analyzed to determine the characters most appropriate for phylogenetic reconstruction. Our results place the New World quail outside all other representative game birds except the cracids. Although in conflict with various morphological analyses, this finding is consistent with the results of DNA-DNA hybridization studies. A model to account for the coupled replacements in the lysozymes is presented. Our results also suggest a rapid but ancient radiation among the Galliformes such that the majority of cytochrome b sequence differences among taxa have accumulated on the terminal branches of the reconstructed phylogenetic trees.

Amino Acid Sequence↗
PubMed1993

Sequence evolution in and around the mitochondrial control region in birds.

By cloning and sequencing 3.4 kilobases of snow goose mtDNA we found that the ND5 gene is followed by the genes for cytochrome b, tRNA(Thr), tRNA(Pro), ND6, tRNA(Glu), the control region, tRNA(Phe), and srRNA. This order is identical to that of chicken, quail, and duck mtDNA but differs from that of mammals and a frog (Xenopus). The mean extent of difference due to base substitution between goose and chicken is generally closer to the same comparison between rat and mouse but less than that between human and cow. For one of the nine regions compared (tRNA(Glu)), the bird differences appear to be anomalous, possibly implicating altered functional constraints. Within the control region, several short sequences common to mammals are also conserved in the birds. Comparison of the goose control region with that of quail and chicken suggests that a sequence element with similarity to CSB-1 duplicated once prior to the divergence of goose and chicken and again on the lineage leading to chicken. Between goose (or duck) and chicken there are four times more transversions at the third positions of fourfold-degenerate codons in mitochondrial than in nuclear genes.

Amino Acid Sequence↗
PubMed1992

Independent origins of New Zealand moas and kiwis.

Two groups of flightless ratite birds existed in New Zealand during the Pleistocene: the kiwis and the moas. The latter are now extinct but formerly included 11 species. We have enzymatically amplified and sequenced approximately 400 base pairs of the mitochondrial 12S rRNA gene from bones and soft tissue remains of four species of moas as well as eight other species of ratite birds and a tinamou. Contrary to expectation, the phylogenetic analysis shows that the kiwis are more closely related to Australian and African ratities than to the moas. Thus, New Zealand probably was colonized twice by ancestors of ratite birds.

Animals↗
PubMed1992

Effect of methylated forms of selenium on cell viability and the induction of DNA strand breakage.

Selenobetaine (SB) and selenobetaine methyl ester (SBME) are methylated selenonium derivatives that undergo metabolism to release methyl selenide and dimethylselenide, respectively, as primary metabolites. Since methylation of selenium is considered to be detoxifying, the toxicologic activity of SB or SBME may differ from that of inorganic forms of selenium, such as selenite, that undergo reduction and can induce cell damage. In this study, the effects of SB, SBME and selenite on the viability and long-term growth potential of a mouse leukemia cell line (L1210) were compared. Treatment with 20 microM selenite reduced the rate of cell doubling and the long-term growth potential of cells as measured by colony-forming ability. These effects of selenite were accompanied by a reduction in DNA integrity, assessed by alkaline elution analysis for single-strand breaks. Exposure to 500 microM SB or SBME for 24 hr reduced the colony-forming ability of cells in the absence of any effect on dye exclusion or induction of single-strand breaks in DNA. Exposure of cells to 500 microM SB or SBME resulted in levels of intracellular selenium similar to those after exposure to 20 microM selenite. These observations indicate that it is possible to maintain high intracellular levels of selenium, by exposure to methylated selenocompounds, without affecting DNA integrity. These findings also suggest that DNA fragmentation resulting from exposure to selenite occurs during its reductive metabolism and not from the accumulation of a methylated metabolite of selenium. The fact that SB or SBME reduced the ability of L1210 cells to form colonies in agar in the absence of either DNA fragmentation or any effect on the ability of treated cells to exclude a vital dye suggests that both methylated compounds alter the long-term proliferative potential of cells via a mechanism(s) distinct from that associated with cell injury and death by necrosis. Efforts are underway to determine the origin of these effects.

Animals↗
PubMed1992

Arterial blood nicotine concentration and coronary vasoconstrictive effect of low-nicotine cigarette smoking.

Low-nicotine cigarettes have been advertised to the public as less harmful to the cardiovascular system. We studied the effects of smoking two low-nicotine cigarettes on arterial and venous blood nicotine levels, hemodynamics, and coronary vascular tone in 12 patients referred for diagnostic coronary arteriography. All were chronic smokers as evidenced by their elevated baseline arterial and venous cotinine blood levels (139 +/- 30 ng/ml and 155 +/- 34 ng/ml, respectively). High-resolution coronary angiograms were evaluated "blindly" before and after smoking. An electronic caliper was used to measure the diameter of disease-free coronary segments of the left anterior descending and circumflex arteries. Arterial nicotine levels rose from 5 +/- 1 ng/ml at baseline to 37 +/- 7 ng/ml (p less than 0.01) after the first cigarette was smoked and to 45 +/- 8 ng/ml (p less than 0.01) after the second cigarette. Venous nicotine levels rose from 8 +/- 2 ng at baseline to 15 +/- 3 ng/ml (p less than 0.05) after the first cigarette and to 20 +/- 3 ng/ml (p less than 0.01) after the second cigarette. After the first cigarette heart rate increased 8 +/- 2 beats/min (p less than 0.003) and double product 1229 +/- 400 beats/min x mm Hg (p less than 0.02). Compared to baseline values, after the second cigarette heart rate increased 9 +/- 1 beats/min (p less than 0.001) and double product 1767 +/- 486 beats/min x mm Hg (p less than 0.01). Systolic, diastolic, and mean blood pressure did not change significantly after either the first or second cigarette.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Catheterization↗