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Biomedical subjects

D E Wilson

Publications and source records attributed to D E Wilson.

At least 55 records · Page 3Linked to original sources
PubMed1994

Effect of positive genetic trend for mature size on age-of-dam adjustment factors for weaning weight in Angus field records.

Weaning weight and postweaning gain field data from the American Angus Association were used to estimate age-of-dam adjustment factors for 205-d weaning weight. A two-trait model was used to take into account all genetic information available in the breed. Correction factors were developed for age-of-dam categories by sex of calf and management (creep or no creep) within maternal-grandsire birth-year groups. The maternal-grandsire birth-year groups were included to determine the need for updating age-of-dam adjustment factors for weaning weight. The mathematical model for 205-d weight included an overall mean, weaning contemporary group, age of dam by sex of calf and management code within maternal-grandsire birth-year group, animal direct effect, maternal genetic effect, permanent environmental effect, and residual error. The model for postweaning gain included an overall mean, postweaning contemporary group, animal direct effect, and residual error. Age-of-dam additive adjustment factors differed from the current factors used for the Angus breed. Young dams did not receive as large an adjustment as the current Angus adjustments recommended. Grouping the age-of-dam categories by birth year of maternal grandsire yielded different additive adjustment factors for 205-d weight. Noncreep calves tended to have larger age-of-dam adjustments than creep-fed calves did. Results indicate the need to consider including age of dam as a fixed effect in the animal model evaluation, so that adjustment factors may be specific to the genetic changes for growth in the breed.

Age Factors↗
PubMed1994

Genetic predisposition to hyperlipidaemia in diabetes: the end of the beginning?

Diabetes mellitus leads to disturbances in lipoprotein homeostasis particularly when there is poor glycaemic control. The resulting abnormalities in concentration and composition of the circulating lipoproteins are modified by inherited variation in the genes coding for apolipoproteins, for the lipoprotein-processing enzymes, and possibly for lipoprotein receptors. Thus, poorly controlled diabetes provides an opportunity to observe the phenotypic effects of recessive mutant alleles that would otherwise be silent. This phenomenon should be considered when one attempts to understand the pathogenesis of variant phenotypes, ones differing from those typical of diabetes mellitus alone. Our understanding of how genetic variation modulates the expression of hyperlipidaemia in diabetes is still rudimentary--it now seems probable that many other genetic conditions affecting lipoprotein metabolism in diabetes will eventually be brought to light.

Alleles↗
PubMed1994

Gastrointestinal bleeding in patients with chronic liver disease: a review.

Most patients with decompensated liver disease who bleed from the gastrointestinal tract bleed from gastroesophageal varices or gastritis (congestive gastropathy). While a variety of pharmacologic and physical therapies are available, optimal treatment and effective prevention of gastrointestinal bleeding have yet to be delineated. In this review, current therapies are compared, as is the effectiveness of prophylaxis. A major problem with evaluating the literature continues to be the disparity between "comparable control groups" using similar protocols.

Esophageal and Gastric Varices↗
PubMed1993

Binding of lipoprotein lipase to heparin. Identification of five critical residues in two distinct segments of the amino-terminal domain.

Binding to heparan sulfate governs many aspects of the physiological action and regulation of the lipolytic enzyme, lipoprotein lipase (LPL). In an attempt to identify the structural determinants which mediate this interaction, basic residues in three segments of the primary sequence of human LPL (residues 147-151, 279-282, and 292-304) were replaced with alanine, either singly or in various combinations, and variant proteins were subjected to affinity chromatography on heparin-Superose. Five basic residues in two distinct segments of the primary sequence were critical determinants of the high affinity for heparin manifested by the active enzyme (R279, K280, R282, K296, R297). By contrast, no such evidence could be detected for basic residues in the first cluster (K147, K148) or for other basic residues in the third cluster (K292, R294, K304), while the evidence for K300 was unresolved. The conformation of this heparin-binding domain can be inferred by reference to the three-dimensional structure of the homologous enzyme, pancreatic lipase (Winkler, F. K., D'Arcy, A., and Hunziker, W. (1990) Nature 343, 771-774). Affinity of the active enzyme for heparin could not be reduced below a threshold, suggesting that other heparin-binding determinants exist elsewhere in the molecule, as supported by recently published evidence (Davis, R. C., Wong, H., Nikazy, J., Wang, K., Han, Q., and Schotz, M. C. (1992) J. Biol. Chem. 267, 21499-21504).

Amino Acid Sequence↗
PubMed1993

Mutations in exon 3 of the lipoprotein lipase gene segregating in a family with hypertriglyceridemia, pancreatitis, and non-insulin-dependent diabetes.

A proband with chylomicronemia, pancreatitis, and non-insulin-dependent diabetes (NIDDM) bears two different mutations in exon 3 of the lipoprotein lipase (LPL) gene: a missense mutation, 75Arg-->Ser, inherited through the paternal line and a truncation, 73Tyr-->Ter, through the maternal line. NIDDM appeared to be independently segregating. The R75S mutant was studied in extracts and media from transfected COS-1 cells. Detectable amounts of catalytically competent R75S LPL suggested destabilization of the active homodimer as with exon 5 mutants (Hata et al. 1992. J. Biol. Chem. 267:20132-20139). Hydrolysis of a short-chain fatty acid ester indicated that R75S does not directly affect activation of LPL by apoC-II. Subjects with NIDDM and wild-type LPL, and nondiabetic middle-aged carriers of the 73Tyr-->Ter truncation had moderate hypertriglyceridemia (260-521 mg/dl) and reduced high density lipoprotein cholesterol. A maternal aunt with NIDDM carried the truncation. Her phenotype (triglycerides of 5,300 mg/dl, eruptive xanthomatosis, and recurrent pancreatitis) was as severe as that in homozygotes or compound heterozygotes. We conclude: (a) diabetic carriers of dysfunctional LPL alleles are at risk for severe lipemia; and (b) the physiologic defects in NIDDM may be additive or synergistic with heterozygous LPL deficiency.

Adolescent↗
PubMed1993

Estradiol stimulates cortisol production by adrenal cells in estrogen-dependent primary adrenocortical nodular dysplasia.

Adrenal glands from a patient with ACTH-independent Cushing's syndrome, whose symptoms worsened during pregnancy and oral contraceptive use, were cultured in different concentrations of estradiol. Estradiol stimulated cortisol secretion in a dose-response manner in the absence of ACTH. Since immunoglobulins G from this patient did not stimulate corticosterone production in a mouse adrenal bioassay, an adrenal-stimulating immunoglobulin is unlikely to be the cause of adrenal hyperfunction in this case. This is the first description of estradiol stimulation of cortisol production by cultured adrenal cells in ACTH-independent Cushing's syndrome.

Adrenal Cortex↗
PubMed1993

Genetic parameter estimates and expected progeny differences for mature size in Angus cattle.

Mature size records collected on Angus cows of 5 to 12 yr of age were used to estimate heritabilities, genetic correlations, and EPD for mature weight and mature height. A total of 256 sires were evaluated using mature size data collected on 2,732 daughters. Data were analyzed using REML procedures with a two-trait sire model to estimate sire and error variances for mature weight and height. Models with and without adjustment of weight for body condition score were investigated. The linear model for weight and height included fixed herd-year-month the records were taken, sire genetic group, random sire, and residual error. Using unadjusted mature weights, heritabilities were .48 +/- .10 for weight and .83 +/- .11 for height. When condition score adjustments were made, heritability estimates were .45 +/- .10 for weight and .83 +/- .11 for height. Genetic (phenotypic) correlations between weight and height were .78(.58) for adjusted data and .66(.54) with no adjustment. Spearman rank correlations between sire EPD for adjusted and unadjusted data were .94 for weight and .99 for height. Two-trait models of mature cow weight with immature weights (birth weight, 205-d weight, 365-d weight) were used to assess genetic relations among mature and immature cow weights. Genetic correlations between mature weight and immature weights were .57 with birth weight, .62 with 205-d weight, and .45 with 365-d weight.

Animals↗
PubMed1993

Genetic parameters for carcass traits estimated from Angus field records.

The American Angus Association has sponsored a carcass evaluation since 1974. The carcass data collected as a part of this program are used by the association to conduct a biannual sire evaluation for carcass merit. This paper presents age-adjustment factors and genetic parameter estimates for carcass traits to be used in the Angus carcass genetic evaluation program. Because of the large range in slaughter ages, age classes were defined as all those animals slaughtered at an age of < or = 480 d and those with a slaughter age > 480 d. Linear and quadratic partial regressions on slaughter age for hot carcass weight (HCW), USDA marbling score (MS), 12th rib longissimus muscle area (LMA), and 12th-rib fat thickness (FT) were estimated within sex and age class. Quadratic age regressions were not significant, nor was the linear age regression coefficient for FT in steers in the > 480-d age class. Heritability estimates for age-constant HCW, MS, LMA, and FT were .31, .26, .32, and .26, respectively. The estimated genetic correlation (rg) between HCW and LMA was .47. The estimated rg between HCW and FT was .38 and between MS and FT was -.13. The linear genetic trends for CWT and LMA were significantly positive at .414 kg/yr and .075 cm2/yr, respectively. The genetic trends for FT and MS were very small but significantly negative at -.004 cm/yr and -.003 units/yr, respectively.

Adipose Tissue↗
PubMed1992

Concanavalin A microspheres for a self-regulating insulin delivery system.

A self-regulating insulin delivery system based on the competitive binding of glucose and p-succinylamidophenyl-alpha-D-glycopyranoside-insulin (SAPG-insulin) to crosslinked concanavalin A (Con A) microspheres (MSs) has been investigated. Con A MSs prepared by a water-in-oil emulsion technique demonstrated properties of binding to glucose and SAPG-insulin (binding constants of 1.25 x 10(3) and 1.28 x 10(4) M-1, respectively) that are similar to the literature values of these properties for unmodified Con A. The retained binding capacity (number of binding sites per molecule) of Con A MSs, produced with 20% of the epsilon-amino groups crosslinked, was approximately 28% that of intact Con A. As a new device, Con A MSs loaded with SAPG-insulin was enclosed in a heat-sealed, surface-modified, porous poly(vinylidene difluoride) membrane pouch. This system showed a pulsatile release pattern for insulin with a short lag time in response to glucose challenges of 50-500 mg/dL. The pattern of release of SAPG-insulin from the devices was studied with varying design parameters, such as surface area, membrane pore size, and loading content of SAPG-insulin.

Binding, Competitive↗
PubMed1992

5,8,11,14-eicosatetraynoic acid-induced destruction of mitochondria in human prostate cells (PC-3).

Culturing human prostate PC-3 cells for 4, 24, or 72 h in the presence of 5,8,11,14-eicosatetraynoic acid (ETYA), an inhibitor of arachidonic acid metabolism and cholesterol biosynthesis, markedly altered the morphology and reduced the number of mitochondria in the treated cells. Using quantitative electron microscopic morphometry, we documented changes in the number, form, area, matrix density, and integrity of the cristae and limiting membranes of mitochondria in cells cultured with ETYA. The inhibition of cholesterol synthesis or the substitution of ETYA for polyunsaturated fatty acids in the inner membrane may participate in the disruption of the mitochondria, which resembles the morphologic sequelae of oxidative stress. If sufficiently extensive, these changes could contribute to the inhibition of cellular proliferation by ETYA.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1992

Application of ultrasound for genetic improvement.

Genetic improvement programs for livestock would be enhanced by the ability to accurately and easily measure body composition of live animals or to make measurements at anatomical reference points that can be used to accurately predict body composition. Advances in ultrasonic technology, such as real-time imagery and portable ultrasound units, have renewed interest among animal scientists working with genetic improvement programs and the livestock industry groups they serve. Ultrasound has been used for more than 30 yr and, for swine, has been demonstrated to improve significantly the accuracy of predicting body composition. However, many studies have shown less success in improving prediction of body composition from the use of ultrasonics to measure live beef cattle and sheep. The swine industry probably will be the first to benefit measurably from use of ultrasound technology in large-scale genetic improvement programs for carcass merit. Considerable research and development is needed before ultrasound technology can be effectively used in similar large-scale programs in the beef cattle and sheep industries.

Animals↗
PubMed1992

Adjusting weight for body condition score in Angus cows.

Weight, height, and body condition score data supplied by the American Angus Association were used to determine the effect of body condition score on cow weight and to compute condition score adjustment factors. Single records on 11,301 cows for weight and 7,769 cows for height were collected at or near weaning, at which time a subjective condition score (9-point scale) was taken. Limited information on extreme scores 1 and 9 allowed only scores 2 through 8 to be included in the analysis. Cows were grouped into age classes corresponding to 2, 3, 4, 5, 6, 7 to 10, and 11+ yr of age. The mathematical model for a weight record included effects of fixed herd, year-month the record was collected, cow age, body condition score, and a random residual error term. The model for height excluded the condition score effect. Effects of herd, year-month, and cow age were highly significant (P less than .0001) for weight and height. Body condition score was a significant source of variation in weight (P less than .0001) and accounted for 16% of the total variation. Adjustment factors for weight (kilograms) by condition score were +116 (score 2), +91 (score 3), +69 (score 4), +39 (score 5), 0 (score 6), -40 (score 7), and -86 (score 8).

Analysis of Variance↗
PubMed1992

Familial dyslipidaemic hypertension and other multiple metabolic syndromes.

Data from several different studies are reviewed suggesting that a subset of hypertension is associated with metabolic abnormalities involving lipids, insulin, and often obesity, all aggregating strongly in families. Persons with 'familial dyslipidaemic hypertension (FDH)' have an especially high risk of early coronary disease. The clinical and biochemical features of FDH are compared with Reaven's Syndrome X, familial combined hyperlipidaemia, dense LDL subfractions, diabetes, impaired glucose tolerance, central and general obesity, pre-diabetes, pre-hypertension, and heterozygous lipoprotein lipase deficiency. Some contribution from major gene effects is suggested in specific subsets reported in several different genetic studies reviewed in this report. It seems likely that multiple metabolic abnormalities are genetically heterogeneous. The data also suggest significant contributions from environmental factors such as diet and physical activity.

Coronary Disease↗
PubMed1991

Successful hyperlipemic pregnancy.

Women with hypertriglyceridemia are prone to gestational pancreatitis, a condition carrying substantial maternal and fetal risk. We describe a 33-year-old woman with familial hypertriglyceridemia who had recurrent hyperlipidemic abdominal crises during previous pregnancies despite dietary fat restrictions. A fifth pregnancy was carried to term without complications after aggressive dietary therapy and intermittent intravenous feeding, administered whenever her triglyceride levels exceeded an arbitrarily selected threshold concentration of 28 mmol/L. The efficacy of this approach may be explained by the published observation that low-fat (high-carbohydrate) isocaloric diets elevate serum triglyceride levels by the oral, but not the intravenous, route in normal individuals. Reduction of this patient's serum triglyceride concentrations by interrupting oral intake and administering intravenous glucose appeared to prevent late-pregnancy pancreatitis and culminated in uncomplicated full-term delivery.

Adult↗
PubMed1991

Elevation of synovial plasminogen activator activity after injection of interleukin-1 alpha into rabbit knee joint.

We investigated production of plasminogen activator (PA) and cartilage degradation induced by injection of recombinant human interleukin-1 (rhIL-1 alpha) in rabbit knees. Rabbits were injected intra-articularly (i.a.) with 100 ng rhIL-1 alpha and necropsied at 0, 3, 6, 18 and 54 h and synovial lavage and articular cartilage were collected. PA activity in the joint lavage was measured using Z-Lys-thiobenzyl ester as a substrate. Cartilage degradation was assessed by quantitating sulfated glycosaminoglycan (S-GAG) to hydroxyproline (Hyp) and appearance of keratan sulfate (KS) in synovial lavage by and ELISA. The PA activity in the lavage of IL-1 injected knees at 3, 6, and 18 h was elevated 8 to 10 fold compared to vehicle controls. At 54 h the activity declined to approximately one third of that seen at the earlier time points. KS in the joint lavage was highest at 18 h, suggesting proteoglycan degradation. The maximal loss of cartilage proteoglycan (S-GAG/Hyp) occurred by 54 h. These observations demonstrate that i.a. injection of IL-1 stimulated the production of PA activity within the rabbit joint. Since elevation of PA activity is followed by cartilage degradation, we investigated effect of anti-inflammatory agents on PA activity and cartilage degradation in this model. We found that triamcinolone, indomethacin and dexamethasone were able to suppress PA activity but not the cartilage degradation. These observations suggest that in this model of cartilage degradation suppression of PA is not sufficient to inhibit cartilage degradation.

Animals↗