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Biomedical subjects

A C Wilson

Publications and source records attributed to A C Wilson.

At least 145 records · Page 8Linked to original sources
PubMed1988

Ancient origin of lactalbumin from lysozyme: analysis of DNA and amino acid sequences.

Parsimony trees relating DNA sequences coding for lysozymes c and alpha-lactalbumins suggest that the gene duplication that allowed lactalbumin to evolve from lysozyme preceded the divergence of mammals and birds. Comparisons of the amino acid sequences of additional lysozymes and lactalbumins are consistent with this view. When all base positions are considered, the probability that the duplication leading to the lactalbumin gene occurred after the start of mammalian evolution is estimated to be 0.05-0.10. Elimination of the phylogenetic noise generated by fast evolution and compositional bias at third positions of codons reduced this probability to 0.002-0.03. Thus the gene duplication may have long preceded the acquisition of lactalbumin function.

Animals↗
PubMed1988

Treatment of type III hyperlipoproteinemia with gemfibrozil to retard progression of coronary artery disease.

Eight type III hyperlipoproteinemic (type III HLP), homozygous E 2/2 patients were enrolled in two periods of long-term diet-gemfibrozil treatment. The combined therapy resulted in highly significant decreases in their low-density lipoprotein cholesterol, very-low density lipoprotein cholesterol, very-low density lipoprotein triglycerides, and increases in their high-density lipoprotein cholesterol during the first treatment period of 24 to 28 months. Type III HLP reasserted itself following an 8-week interruption of gemfibrozil therapy. Resumption of gemfibrozil therapy again lowered the high lipid-lipoprotein concentrations of these patients toward normal. Tuboeruptive xanthomata, palmar xanthoma, and xanthoma striata palmare subsided with treatment. Follow-up coronary arteriograms performed 2.5 to 3.0 years after initiation of diet-drug treatment showed stabilization of coronary arterial lesions, which was associated with improvement in exercise tolerance.

Adult↗
PubMed1988

Polypoid neurilemmoma of the trachea: an unusual cause of major airway obstruction.

Neurilemmomas (schwannomas) of the trachea are extremely rare. A case of near-total obstruction of the trachea by an intraluminal polypoid neurilemmomas is reported. Computerized tomographic imaging gave the exact localization of the polyp and the attachment of its stalk. Endoscopic excision has left the patient with an excellent prognosis and little chance of recurrence.

Adult↗
PubMed1987

Evidence for a warfarin-sensitive serum factor that participates in factor X activation by Lewis lung tumor cells.

Mouse Lewis lung (LL) carcinoma cells possess a factor X activator (procoagulant) that is inhibited in vivo by warfarin treatment or diet-induced vitamin K deficiency. This inhibition suggests that vitamin-K-dependent proteins are involved in LL cell activation of factor X. A LL primary tumor clone (LL13) was isolated which contained a warfarin-sensitive vitamin-K cycle of metabolism and expressed factor X procoagulant activity. LL13 cells exposed to media containing warfarin or deficient in vitamin K grew as well as cells in normal media, and activated factor X to similar extents. In contrast, administration of warfarin to mice bearing LL13 cells inhibited factor X procoagulant activity as well as the vitamin K cycle of metabolism in the primary tumors. In relation to LL13 cells grown in media containing fetal bovine serum, those incubated for 20 hr in media containing mouse serum or the sera from LL13-bearing mice exhibited 9- to 10-times higher levels of factor X procoagulant activity. However, LL13 cells exposed to media containing the sera of warfarin-treated LL-13-bearing mice or to barium-sulfate-adsorbed normal mouse serum activated factor X much less efficiently. Collectively, these data suggest that inhibition of vitamin K function in LL cells does not affect the extent of factor X activation and thus the intrinsic factor X procoagulant is not a vitamin-K-dependent protein. They further suggest that both a warfarin-sensitive (vitamin-K-dependent) protein present in normal mouse serum and a LL13 cell component participate in factor X procoagulant activity.

Animals↗
PubMed1987

Identification of vitamin K1 chromenol--a novel metabolite of vitamin K1 formed in vitro by a component in blood.

A newly recognized metabolite of vitamin K1, vitamin K1 chromenol, is produced when the vitamin is added to the plasma or serum of a number of species. The metabolite was identified by comparison of its uv and mass spectra and high-performance liquid chromatographic retention times with those of the synthetic vitamin K1 chromenol. In aqueous solution vitamin K chromenol decomposed to a variety of products and reacted with nucleophilic substances. Optimal conditions for its formation and evidence that chromenol formation may be an enzyme catalyzed reaction are presented.

Animals↗
PubMed1987

Length mutations in human mitochondrial DNA: direct sequencing of enzymatically amplified DNA.

A specific segment of mitochondrial DNA from 18 people was examined by two methods of direct DNA sequencing. This segment includes a small noncoding region (V) shown before by restriction analysis to exhibit length polymorphism. All 11 of the human mtDNAs previously reported to have a deletion in this region proved to lack one of the two adjacent copies of a 9-base-pair sequence normally present in human mtDNAs. Phylogenetic analysis suggests that this deletion occurred only once during the evolution of modern types of human mtDNA and that it will be a valuable anthropological marker for peoples of East Asian origin. The one human mtDNA reported to have an addition in region V differs from the wild type by two mutations in the first copy of the 9-base-pair sequence: one transition and an addition of four cytosines, thereby producing a run of 11 cytosines. One of the direct DNA sequencing methods uses a single oligonucleotide primer to facilitate dideoxy sequencing from purified mtDNA templates. The second, more successful, method first amplifies this mtDNA segment enzymatically with two flanking primers (the "polymerase chain reaction") and then uses a third primer for DNA sequencing. This latter method, which works on the DNA extracted from small amounts of blood as well as on purified mtDNA, is shown to be a rapid means of defining sequence variants without purifying and cloning the same DNA segment from many individuals.

Base Sequence↗
PubMed1987

Calibration of mitochondrial DNA evolution in geese.

Mitochondrial DNA was purified from five American species of geese representing the genera Anser and Branta, which have fossil records. The results of electrophoretic comparisons of about 75 fragments per individual produced by 14 restriction enzymes imply that the mean extent of sequence divergence between species of Anser and Branta is about 9%. Fossil evidence suggests that these two groups of geese had a common ancestor 4-5 million years ago. Thus, the mean rate of sequence divergence in goose mitochondrial DNA is not far from 2% per million years, the value in mammals.

Animals↗
PubMed1987

Recruitment of lysozyme as a major enzyme in the mouse gut: duplication, divergence, and regulatory evolution.

Two major types of lysozyme c (M and P) occur in the mouse genus, Mus, and have been purified from an inbred laboratory strain (C58/J) of M. domesticus. They differ in physical, catalytic, and antigenic properties as well as by amino acid replacements at 6 of 49 positions in the amino-terminal sequence. Comparisons with four other mammalian lysozymes c of known sequence suggest that M and P are related by a gene duplication that took place before the divergence of the rat and mouse lineages. M lysozyme is present in most tissues; achieves its highest concentration in the kidney, lung, and spleen; and corresponds to the lysozyme partially sequenced before from another strain of M. domesticus. In M. domesticus and several related species, P lysozyme was detected chiefly in the small intestine, where it is probably produced mainly by Paneth cells. A survey of M and P levels in 22 species of muroid rodents (from Mus and six other genera) of known phylogenetic relationships suggests that a mutation that derepressed the P enzyme arose about 4 million years ago in the ancestor of the housemouse group of species. Additional regulatory shifts affecting M and P levels have taken place along lineages leading to other muroid species. Our survey of 187 individuals of wild house mice and their closest allies reveals a correlation between latitude of origin and level of intestinal lysozyme.

Amino Acid Sequence↗
PubMed1987

Evolution in bacteria: evidence for a universal substitution rate in cellular genomes.

This paper constructs a temporal scale for bacterial evolution by tying ecological events that took place at known times in the geological past to specific branch points in the genealogical tree relating the 16S ribosomal RNAs of eubacteria, mitochondria, and chloroplasts. One thus obtains a relationship between time and bacterial RNA divergence which can be used to estimate times of divergence between other branches in the bacterial tree. According to this approach, Salmonella typhimurium and Escherichia coli diverged between 120 and 160 million years (Myr) ago, a date which fits with evidence that the chief habitats occupied now by these two enteric species became available that long ago. The median extent of divergence between S. typhimurium and E. coli at synonymous sites for 21 kilobases of protein-coding DNA is 100%. This implies a silent substitution rate of 0.7-0.8%/Myr--a rate remarkably similar to that observed in the nuclear genes of mammals, invertebrates, and flowering plants. Similarities in the substitution rates of eucaryotes and procaryotes are not limited to silent substitutions in protein-coding regions. The average substitution rate for 16S rRNA in eubacteria is about 1%/50 Myr, similar to the average rate for 18S rRNA in vertebrates and flowering plants. Likewise, we estimate a mean rate of roughly 1%/25 Myr for 5S rRNA in both eubacteria and eucaryotes. For a few protein-coding genes of these enteric bacteria, the extent of silent substitution since the divergence of S. typhimurium and E. coli is much lower than 100%, owing to extreme bias in the usage of synonymous codons. Furthermore, in these bacteria, rates of amino acid replacement were about 20 times lower, on average, than the silent rate. By contrast, for the mammalian genes studied to date, the average replacement rate is only four to five times lower than the rate of silent substitution.

Bacteria↗
PubMed1987

Tempo and mode of sequence evolution in mitochondrial DNA of Hawaiian Drosophila.

Sequence comparisons were made for up to 667 bp of DNA cloned from 14 kinds of Hawaiian Drosophila and five other dipteran species. These sequences include parts of the genes for NADH dehydrogenase (subunits 1, 2, and 5) and rRNA (from the large ribosomal subunit). Because the times of divergence among these species are known approximately, the sequence comparisons give insight into the evolutionary dynamics of this molecule. Transitions account for nearly all of the differences between sequences that have diverged by less than 2%: for these sequences the mean rate of divergence appears to be about 2%/Myr. In comparisons involving greater divergence times and greater sequence divergence, relatively more of the sequence differences are due to transversions. Specifically, the fraction of these differences that are counted as transversions rises from an initial value of less than 0.1 to a plateau value of nearly 0.6. The time required to reach half of the plateau value, about 10 Myr, is similar to that for mammalian mtDNA. The mtDNAs of flies and mammals are also alike in the shape of the curve relating the percentage of positions at which there are differences in protein-coding regions to the time of divergence. For both groups of animals, the curve has a steep initial slope ascribable to fast accumulation of synonymous substitutions and a shallow final slope resulting from the slow accumulation of substitutions causing amino acid replacements. However, the percentage of all sites that can experience a high rate of substitution appears to be only about 8% for fly mtDNA compared to about 20% for mammalian mtDNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Mitochondrial DNA of the extinct quagga: relatedness and extent of postmortem change.

Sequences are reported for portions of two mitochondrial genes from a domestic horse and a plains zebra and compared to those published for a quagga and a mountain zebra. The extinct quagga and plains zebra sequences are identical at all silent sites, whereas the horse sequence differs from both of them by 11 silent substitutions. Postmortem changes in quagga DNA may account for the two coding substitutions between the quagga and plains zebra sequences. The hypothesis that the closest relative of the quagga is the domestic horse receives no support from these data. From the extent of sequence divergence between horse and zebra mitochondrial DNAs (mtDNAs), as well as from information about the fossil record, we estimate that the mean rate of mtDNA divergence in Equus is similar to that in other mammals, i.e., roughly 2% per million years.

Animals↗
PubMed1987

The effects of polyoxyethylated cholesterol feeding on hepatic cholesterol synthesis and intestinal cholesterol absorption in rats.

Adduction of ethylene glycol moieties to the 3-hydroxy position of cholesterol produces polyoxyethylated cholesterol (POEC), a water-soluble compound that suppresses cholesterol synthesis and esterification in cultured human fibroblasts. Feeding Sprague-Dawley rats a diet containing 2% (wt/wt) POEC with 10 ethoxy groups resulted in a 3-fold increase in hepatic 3-hydroxy-3-methylglutaryl-CoA reductase activity compared to activity in rats pair-fed a diet of standard rat chow. POEC with an average of 20 ethoxy groups (POEC-20) caused comparable changes in hepatic [2-14C]acetate incorporation into non-saponifiable lipids under ad libitum feeding conditions, significantly reduced cholesterol absorption (18% vs 57%), and increased fecal excretion of neutral steroids (5.1 vs 2.0 mg/g food intake). POEC-20 also reduced cholesterol absorption in rats fed a diet enriched with 2% cholesterol (11% vs 31%). Histologic studies of intestinal mucosa and hepatic tissues from rats fed POEC showed no pathologic changes. These experiments indicate that POEC reduces cholesterol absorption and causes compensatory increases in hepatic cholesterol synthesis.

Animals↗
PubMed1987

Regulatory and structural genes for lysozymes of mice.

The molecular and genetic basis of large differences in the concentration of P lysozyme in the small intestine has been investigated by crossing inbred strains of two species of house mouse (genus Mus). The concentration of P in domesticus is about 130-fold higher than in castaneus. An autosomal genetic element determining the concentration of P has been identified and named the P lysozyme regulator, Lzp-r. The level of P in interspecific hybrids (domesticus X castaneus) as well as in certain classes of backcross progeny is intermediate relative to parental levels, which shows that the two alleles of Lzp-r are inherited additively. There are two forms of P lysozyme in the intestine of the interspecific hybrid--one having the heat stability of domesticus P, the other being more stable and presumably the product of the castaneus P locus. These two forms occur in equal amounts, and it appears that Lzp-r acts in trans. The linkage of Lzp-r to three structural genes (Lzp-s, Lzm-sl, and Lzm-s2), one specifying P lysozyme and two specifying M lysozymes, was shown by electrophoretic analysis of backcrosses involving domesticus and castaneus and also domesticus and spretus. The role of regulatory mutations in evolution is discussed in light of these results.

Aging↗
PubMed1987

Open heart surgery in the elderly.

Of 3254 open heart surgical cases performed since 1972, 126 patients (3.9%) were 70 years of age or older. The mean age was 72 years, the oldest being 82. Sixty-seven per cent were male. The following procedures were performed: coronary artery bypass grafting (CABG) 51, aortic valve replacement (AVR) 44, AVR + CABG 16, mitral valve replacement (MVR) 3, MVR + CABG 6, MVR + AVR 4, and other, 2. Of those undergoing CABG, 33% came from the Coronary Care Unit and 24% had left main coronary artery stenosis. There was one peri-operative death (2.0%). Of those undergoing AVR, 43% had coronary artery disease and 13% triple vessel disease. Operative mortality for AVR, and AVR + CABG was 11.4% (5/44) and 18.8% (3/16), respectively. Twenty-six per cent of operative survivors had significant postoperative complications (excluding atrial arrhythmias). The postoperative hospital stay for CABG, AVR and other cases was 11, 13 and 16 days, respectively. Seven year survival of all patients was 61.2 +/- 6.5% (+/- 1 SE) and for AVR +/- CABG was 51.5 +/- 8.6%. Five year survival for CABG was 83.9 +/- 6.3%. We conclude that, in selected cases, CABG can be performed safely in the elderly. Although valvular and combined surgery may result in significant morbidity and mortality, the satisfactory long term results in survivors justifies surgery in this group of patients.

Aged↗
PubMed1987

Genetic differences in the histochemically defined structure of oligosaccharides in mice.

A wide range of tissues from three interfertile species of mice and an interspecific hybrid was examined with lectins conjugated to peroxidase to localize specifically glycoconjugates containing terminal alpha-N-acetylgalactosamine, alpha-galactose, and alpha-fucose, and the terminal disaccharide galactose-(beta 1----3)-N-acetylgalactosamine. This battery of lectins disclosed marked heterogeneity of glycoconjugates in different histological sites in a given animal and even between cells in a presumably homogeneous cell population within an organ. No variation with any lectin was observed between individuals of two closely related inbred strains of Mus domesticus at any specific histological or cytological site. In contrast, littermates of an outbred strain of Mus castaneus differed in binding of certain lectins at various sites, attesting to a genetic basis for individual variation. Hybrids between castaneus and domesticus mice also showed individual variation. Moreover, extensive differences between the mouse species were demonstrable with every lectin in glycoconjugates of stored secretions, Golgi cisternae, and apical or basolateral plasmalemma in many cell types. Totaling the differences in tabulated staining intensities for each possible species pair gave a measure of the overall extent of difference at 53 histological sites. According to this measure, the three species are about equally divergent from one another. Some differences between species appeared to depend on histological rather than histochemical variation, as, for example, a greater abundance of granular duct cells in the sublingual and submandibular glands in Mus hortulanus. Other differences were apparently derived from pathological change, as exemplified by casts and lymphoid infiltrates in kidney and structurally atypical submandibular gland lobules in Mus castaneus, and possibly by infiltrating cells in intestinal lamina propria and epithelium in Mus castaneus and hortulanus.

Acetylgalactosamine↗