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Biomedical subjects

D E Wilson

Publications and source records attributed to D E Wilson.

At least 109 records · Page 6Linked to original sources
PubMed1987

Antisecretory and mucosal protective actions of misoprostol. Potential role in the treatment of peptic ulcer disease.

Misoprostol, a synthetic methyl ester analogue of prostaglandin E1, inhibits basal, nocturnal, and stimulated gastric acid secretion. In doses of 400 to 1,200 micrograms daily, misoprostol accelerates the healing of duodenal and gastric ulcers in humans. In addition to its antisecretory actions, misoprostol has gastroduodenal mucosal protective (cytoprotective) effects in animals and in humans. In humans, these cytoprotective actions have been demonstrated in acid-dependent studies using non-antisecretory doses and in acid-independent studies using antisecretory doses. Patients with peptic ulcer disease may have a relative deficiency of mucosal prostaglandin synthesis as compared with nonulcer control subjects. In addition, patients who consume nonsteroidal anti-inflammatory drugs and those who are cigarette smokers may also have depressed gastric mucosal prostaglandin synthesis. There is some evidence that misoprostol reverses the deleterious effect of smoking on duodenal ulcer healing and that it is effective in treating and preventing mucosal damage induced by nonsteroidal anti-inflammatory drugs and alcohol.

Alprostadil↗
PubMed1987

Provisional assignment of the gene for uridine monophosphatase-2 (Umph-2) to mouse chromosome 11.

The segregation of the mouse gene for uridine monophosphatase-2 (Umph-2) was examined in 14 independent mouse-Syrian hamster hybrids and 10 hybrid subclones. Umph-2 cosegregated with the mouse galactokinase (Glk) gene in 23 of the 24 hybrids and showed at least four discordances with all other mouse marker isozymes examined. The observed synteny of Umph-2 and Glk, which has also been observed in humans, indicates that the mouse Umph-2 gene is on chromosome 11.

Animals↗
PubMed1987

Effects of estrogen/progestin agents on plasma retinoids and chylomicron remnant metabolism.

Women using estrogen-progestin oral contraceptive agents have a marked decrease in the activity of hepatic triglyceride lipase, an enzyme believed to be involved in the catabolism of lipoprotein remnants. The hypothesis that women receiving these agents have defective remnant processing resulting in elevated chylomicron remnant concentrations in plasma was tested. Retinyl esters, which in humans are transported by intestinally-derived lipoproteins, were used to estimate chylomicron and chylomicron remnant concentrations. Women on a variety of oral contraceptive agents had increased plasma triglyceride concentrations, but only minimally increased fasting retinyl ester concentrations. Retinol and retinyl binding protein were elevated to about 150% of controls (p less than 0.001). Retinyl ester concentrations during active fat absorption were then measured in a second group of women taking a single preparation. Three-hour retinyl ester levels were lower in the treated group than control (p less than 0.05), but the difference had disappeared at six hours. Postheparin plasma hepatic triglyceride lipase was reduced by 46% in the treated group (p less than 0.05). Thus despite reduction in hepatic lipase activity, there was no accumulation of retinyl esters in the contraceptive-treated women to suggest impaired remnant processing.

Adult↗
PubMed1987

Pantethine lipomodulation: evidence for cysteamine mediation in vitro and in vivo.

Recent human studies suggest rapid in vivo hydrolysis of the lipid-lowering drug, pantethine, to the vitamin pantothenic acid and the small aminothiol compound, cysteamine. To test whether the active agent is a hydrolysis product, we repeated three experimental models of pantethine's effect with pantothenate and cysteamine. In vitro experiments with human fetal fibroblasts showed equivalent modulation of cholesterol and methyl sterol synthesis by pantethine, cysteamine, or cystamine (the disulfide of cysteamine), but pantothenate had no effect. Similarly, in vivo experiments with 0.5% cholesterol-fed rabbits showed oral pantethine or equimolar cystamine significantly lowered plasma cholesterol, while pantothenate, cystine, and 2-hydroxyethyl disulfide did not. Lastly, diabetic male rats (40 mg/kg streptozotocin) fed 0.1% pantethine and lower plasma free fatty acids after 2 weeks than controls, an effect not seen with pantothenate and largely duplicated by cystamine. The efficacy of pantethine has previously been attributed to altered vitamin metabolism and increased coenzyme A concentration. Pantethine did increase CoA levels 45% in rat liver homogenates while equivalent amounts of cystamine or pantothenate did not. However, a causal relationship between CoA levels and pantethine's action as a hypolipemic agent has never been shown. At least in 3 independent experimental models, the lipomodulating effect of pantethine appears instead to be mediated by the hydrolysis product cysteamine.

Animals↗
PubMed1987

Relationship of organ lipoprotein lipase activity and ketonuria to hypertriglyceridemia in starved and streptozocin-induced diabetic rats.

Although lipoprotein lipase (LPL) is believed to be rate limiting in the catabolism of triglyceride-rich lipoproteins, LPL activity has not correlated with plasma triglyceride concentrations in experimental rat diabetes. To gather more information about this enzyme system in diabetes, LPL activities were measured in representative tissues from control and streptozocin-induced diabetic rats fed fat-free chow and in 48-h-starved animals. The DNA content of each tissue was determined so that LPL activity could be expressed in a way that was unaffected by tissue wasting. Diabetic animals lost approximately 20% of their body mass. Adipose tissue and soleus muscle cell masses were reduced, and there was marked fat atrophy at necropsy. Adipose tissue LPL was decreased in both starved and diabetic animals, whereas skeletal muscle activities were variably affected. Lipase content and distribution among the individual organs were calculated with published data for rat carcass composition. In diabetic rats, total LPL (adipose tissue, muscle, and parenchymal organs) was reduced by nearly two-thirds so that skeletal muscle became the predominant source of LPL. Ketonuria was less frequent in diabetic than in starved rats (P less than .018) despite their severe wasting. Serum triglyceride concentrations were higher in ketonuric than nonketonuric diabetic animals, and severe hypertriglyceridemia was seen exclusively in heavily ketonuric animals. These observations together with published information suggest that plasma triglyceride concentrations in the rat model are determined by a complex interplay between very-low-density lipoprotein synthesis, the capacity of the LPL removal system, properties of the lipoprotein substrate, and other unidentified factors.

Adipose Tissue↗
PubMed1987

Prostaglandins in peptic ulcer disease. Their postulated role in the pathogenesis and treatment.

Prostaglandins are important in the pathophysiology of peptic ulcer disease and possibly in its prevention and treatment as well. Prostaglandins have been shown to inhibit gastric secretion, stimulate bicarbonate secretion, and increase gastric blood volume. Pretreatment with prostaglandins has recently been found to promote rapid restitution of the superficial epithelium of the gastric mucosa and preservation of the deeper layers. These effects and their degree of importance to an individual patient may depend on the insulting agent. Orally administered prostaglandin analogues have been helpful in some patients who failed to heal with standard ulcer treatment and in smokers, who usually do not heal as well as nonsmokers. They have also been effective in persons at high risk for gastric lesions, such as chronic consumers of nonsteroidal antiinflammatory drugs or alcohol. Recent reports show that persons with peptic ulcer disease may produce fewer prostanoids than others, so replacement therapy may be useful in preventing damage of the gastroduodenal mucosa.

Administration, Oral↗
PubMed1986

Synergy between recombinant interleukin 2 (rIL 2) and IL 2-depleted lymphokine-containing supernatants in facilitating allogeneic human cytolytic T lymphocyte responses in vitro.

Supernatants from human mixed leukocyte cultures or lectin-depleted supernatants from cultures of PHA-activated human peripheral blood leukocytes were depleted of IL 2 by passage over an anti-human rIL2 immunoadsorbent column. The column eluates were concentrated, dialyzed, and tested for their ability to synergize with human rIL 2 in facilitating human cytolytic T lymphocyte (CTL) responses to allogeneic, uv-irradiated HT144 melanoma cells in vitro. CTL were generated in the presence of 1 X 10(-4) M hydrocortisone sodium succinate in order to minimize the generation of nonspecific lymphokine-activated killer (LAK) cells. IL 2-depleted lymphokine-containing supernatant (LKS), alone or in the presence of less than or equal to U/ml rIL 2 did not stimulate significant CTL responses. Recombinant IL 2 at greater than 2 U/ml stimulated weak CTL responses in the absence of LKS. However, strong synergistic CTL responses were observed when both IL 2-depleted LKS and greater than 2 U/ml rIL 2 were added to the cultures. CTL generated in these cultures could be distinguished from nonspecific LAK cells on the basis of their i) specificity, ii) T3 phenotype, and iii) kinetics of generation. Nevertheless, rIL 2 and IL 2-depleted LKS were sometimes observed to synergize in facilitating the generation of nonspecific LAK cells as well as the generation of specific CTL. When the times at which rIL 2 and IL 2-depleted LKS were added to the cultures were varied, IL 2 was found to be required early in CTL responses, whereas the synergistic factor(s) in LKS seemed to act later. Recombinant human interferon-gamma was unable to replace LKS in synergizing with rIL 2 to elicit CTL responses. In summary, these experiments suggest that LKS contains a late-acting factor(s), antigenically distinct from IL 2, which synergizes with IL 2 in facilitating human CTL responses.

Biological Products↗
PubMed1986

Evidence that men with familial hypercholesterolemia can avoid early coronary death. An analysis of 77 gene carriers in four Utah pedigrees.

To study the genetic influence on serum cholesterol levels and early coronary heart disease, 1,134 individuals were screened from 18 Utah pedigrees. In most pedigrees, serum cholesterol appeared to be a purely polygenic trait, with 54% heritability. In four pedigrees with dominant familial hypercholesterolemia, male heterozygotes had a mean serum cholesterol level of 352 mg/dL, myocardial infarction at an average age of 42 years, and coronary death at an average age of 45 years. An informative pedigree structure allowed the identification of four ancestral males born before 1880 who carried this lethal gene and survived to ages 62, 68, 72, and 81 years. This suggests that some healthy life-style factors protected these men against the expression of a gene that has led to coronary disease by age 45 years in all of their heterozygous great-grandsons. One heterozygote showed a drop in serum cholesterol level from 426 to 248 mg/dL, with strict adherence to a low-fat diet without drugs. These observations should help encourage physicians to try harder to identify and help such individuals.

Adult↗
PubMed1986

Therapeutic aspects of prostaglandins in the treatment of peptic ulcer disease.

Studies of antisecretory compounds such as the H2-receptor antagonists have altered therapy and enhanced the understanding of peptic ulcer disease (PUD). While it is agreed that the dictum "no acid, no ulcer" is valid, acid hypersecretion does not appear to be the major determinant in a significant number of ulcer patients. More careful consideration of mucosal integrity in the pathogenesis of PUD is therefore necessary. A small but significant number of patients (5-15%) do not heal, despite the use of effective antiulcer drugs. Moreover, the posthealing recurrence rate may reach 75% after treatment is discontinued, and nearly one third of cigarette-smoking patients on maintenance therapy may suffer recurrences. Prostaglandins (PGs) are particularly important as potent antisecretory and effective antiulcer agents. In addition, recognition of their cytoprotective effects has stimulated research into the understanding and importance of mucosal protection and mucosal defense mechanisms. Animal studies show that PGs at nonantisecretory dosages prevent the development of gastric ulcers caused by virtually any insult. In humans, PGs prevent the mucosal damage caused by aspirin and ethanol. In some studies, the maintenance of normal mucosal integrity has been linked to normal mucosal production of PGs. Therefore, it is possible that exogenous PGs may be effective in patients whose ulcers do not heal with conventional therapy. They may reduce the recurrence of ulcers, particularly in those patients whose defect in mucosal integrity appears to be the major problem. Furthermore, in those patients subjected to the toxic effects of alcohol ingestion, nonsteroidal antiinflammatory drugs, antineoplastic drugs, and stress, exogenous PGs may prevent mucosal lesions. As such, PGs could be the ideal antiulcer drug.

Bicarbonates↗
PubMed1986

Effects of misoprostol on gastric acid and mucus secretion in man.

Misoprostol, a synthetic prostaglandin E1 analog, at doses of 200, 400, or 800 micrograms, and placebo were administered orally in random fashion to eight healthy male volunteers. The effects on basal and pentagastrin (0.6 microgram/kg/hr)-stimulated acid and mucus (N-acetylneuraminic acid measurement) secretion were then determined. Misoprostol in 200-, 400-, and 800-micrograms doses reduced basal acid secretion by 91%, 93%, and 93%, respectively. Mean 2-hr acid secretion was reduced by 27%, 33% (P less than 0.01), and 51% (P less than 0.01), respectively. Reductions in secretory volumes paralleled acid changes. Mucus secretion increased by 37%, 82%, and 95% during the basal period following misoprostol doses of 200, 400, and 800 micrograms, respectively. Increase in mucus of 27%, 31%, and 38% was observed during maximal acid inhibition (1-30 min) by misoprostol in 200-, 400-, and 800-micrograms doses. The concentration of gastric juice mucus was significantly increased. Subjects experienced no significant side effects during the study, and there were no significant changes in hematological or chemical blood studies. Misoprostol, a potent inhibitor of gastric acid secretion, also stimulates mucus secretion. This mucogenic effect may be important in the mucosal protective action of misoprostol and its antiulcer efficacy in man.

Adult↗
PubMed1986

Assignment of the human gene for beta-glycerol phosphatase to chromosome 8.

The segregation of the human gene for beta-glycerol phosphatase (GPB) was examined in human-Syrian hamster and human-Chinese hamster somatic cell hybrids. Electrophoretic analysis of the GPB in hybrids suggested that the enzyme is a dimer. Human GPB cosegregated with chromosome 8 in the twenty-five hybrids examined.

Animals↗
PubMed1986

Assignment of the human gene for uridine 5'-monophosphate phosphohydrolase (UMPH2) to the long arm of chromosome 17.

Two distinct isozymes of uridine 5'-monophosphate phosphohydrolase (UMPH) have been identified in mammalian cells. Both of these isozymes hydrolyse other pyrimidine nucleotides. One of the isozymes, UMPH2, is more active against deoxy-nucleotides than non-deoxy-nucleotides and has a wider substrate specificity. We examined the segregation of the human gene for UMPH2 in human-mouse somatic cell hybrids. Electrophoretic analysis of UMPH2 in hybrids suggested that the enzyme is a dimer. Human UMPH2 cosegregated with the long arm of chromosome 17 in the nineteen hybrids examined. The ease of separation of the rodent and human isozymes of UMPH2 and the relative simplicity of the enzyme assay suggest that UMPH2 may be a more useful marker gene for chromosome 17 than galactokinase.

5'-Nucleotidase↗
PubMed1986

Tagliacotian cross-arm flap reconstruction of facial defects.

The tagliacotian cross-arm flap finds its basis in one of the oldest reconstructive techniques known, the brachial flap of Gaspar Tagliacozzi. Although not commonly employed today, it remains useful in difficult orbital and nasal reconstructions. Our report deals with the historic development, applicability, timing, and technique of this procedure and is well illustrated by a case report. Advantages of the tagliacotian flap include no additional scarring in the exposed area and a hidden donor site. A considerable amount of usually non-hair-bearing tissue can be transferred without sacrifice of valuable muscle and without special surgical techniques. The tagliacotian cross-arm flap should be considered when local and regional tissue supply is inadequate, when aesthetic desires of the patient preclude additional local scarring, and when time allows for the training and transfer of this flap.

Adult↗
PubMed1986

Apolipoprotein E-containing lipoproteins and lipoprotein remnants in experimental canine diabetes.

The effects of diabetes on plasma lipoproteins were examined in a cohort of control and streptozocin-alloxan diabetic beagles fed either standard rations or an atherogenic cholesterol-supplemented diet. Lipoprotein cholesterol, triglyceride, and retinyl ester concentrations were measured in fractions separated by density gradient ultracentrifugation. Individual lipoprotein classes and apolipoproteins were assessed by electrophoresis. Postheparin plasma lipoprotein triglyceride lipase activities were also examined. In the absence of added dietary cholesterol, diabetic animals became hypercholesterolemic with relatively increased low-density (LDL) and decreased high-density (HDL) lipoprotein cholesterol concentrations. Apolipoprotein E-containing beta- to alpha 2-migrating HDL1 (HDLc) appeared in rho = 1.020-1.080 g/ml subfractions, whereas alpha 1-migrating typical HDL (rho = 1.06-1.21 g/ml) was reduced. In comparison to nondiabetic cholesterol-fed animals, diabetic cholesterol-fed animals had increased cholesterol (but not triglyceride) concentrations in very-low- and intermediate-density classes. These classes contained retinyl esters and low-molecular-weight apolipoprotein B (components of intestinal lipoprotein remnants) as well as apolipoprotein E and high-molecular-weight apolipoprotein B. These findings could not be explained by decreased postheparin plasma lipoprotein lipolytic activities. Increased plasma concentrations of HDLc in poorly controlled diabetic dogs may reflect a pathologic disturbance in the excretory limb of cholesterol transport from peripheral cells to the liver. In addition, exaggerated retention of lipoprotein remnants in cholesterol-fed diabetic dogs may contribute to increased delivery of cholesterol to extrahepatic tissues. This model appears to be suitable for physiologic studies of the effects of diabetes on reverse cholesterol transport.

Animals↗
PubMed1986

Estimates of beef growth trait variances and heritabilities determined from field records.

Variance components were estimated from field-collected performance records for use in national beef sire evaluation mixed-model programs. Estimates of residual error variances (sigma 2e), sire effect variances (sigma 2s) and dam effect variances (sigma 2d) were obtained for the American Hereford and the American Angus breeds for each of three growth traits: birth weight, weaning weight and postweaning gain. Estimates obtained for birth weight were sigma 2e, 8.43 and 9.26 kg2; sigma 2s, 1.34 and .66 kg2; and sigma 2d, 3.24 and 3.70 kg2 for the Hereford and Angus breeds, respectively. Estimates obtained for weaning weight were sigma 2e, 438.09 and 267.38 kg2; sigma 2s, 20.37 and 17.13 kg2; and sigma 2d, 162.25 and 157.28 kg2 for the Hereford and Angus breeds, respectively. Estimates obtained for postweaning gain were sigma 2e, 425.75 and 374.33 kg2; sigma 2s, 20.08 and 16.49 kg2; and sigma 2d, 41.74 and 48.61 kg2 for the Hereford and Angus breeds, respectively.

Analysis of Variance↗
PubMed1986

Within-herd phenotypic, genetic and environmental trend lines for beef cattle breeders.

Computational procedures were developed to compute within-herd phenotypic, genetic and environmental trend lines on a breed-wide basis by using best linear unbiased estimates of fixed effects and predictors of random sire and dam genetic effects. Procedures were demonstrated by using weaning weight performance records from 20 herds participating in the American Angus Herd Improvement Program. Current evaluation procedures used by several beef breed associations make it possible to provide such information to breeders on a routine basis, along with within-herd breeding values. The within-herd genetic trends are relative to the national genetic evaluation base. Procedures are summarized in addition to presentation of within-herd trend lines for four of the 20 herds, demonstrating the utility of such information to breeders, along with a discussion of several alternative presentation formats.

Animal Husbandry↗