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Biomedical subjects

D R Nelson

Publications and source records attributed to D R Nelson.

At least 19 recordsLinked to original sources
PubMed1995

Vascular tissue plasminogen activator and the development of coronary artery disease in heart-transplant recipients.

BACKGROUND: An aggressive and potentially fatal form of coronary artery disease may develop after cardiac transplantation. We studied the role of vascular tissue plasminogen activator (t-PA), the primary mediator of fibrinolysis, in the development of this problem. METHODS: We studied 78 consecutive recipients of cardiac allografts over a five-year period, and we collected follow-up data over a mean (+/- SE) of 32.5 +/- 2.0 months. The patients were studied with ventricular function tests, serial endomyocardial biopsies (16.6 +/- 0.5 per patient), and annual coronary angiography. Measurements of t-PA and its inhibitor were performed immunocytochemically on unfixed cryostat sections of endomyocardial-biopsy specimens with the use of monoclonal antibodies to t-PA and its inhibitor. RESULTS: In biopsy specimens obtained during the first three months of follow-up, 38 allografts had a normal distribution of t-PA in arteriolar smooth-muscle cells, whereas in 40 allografts there was depletion of t-PA that persisted in subsequent follow-up. Coronary artery disease developed during follow-up in 31 of 40 allografts (78 percent) with depletion of t-PA, but the disease developed in only 9 of the 38 allografts (24 percent) with normal t-PA levels (P < 0.001). Allografts with depletion of t-PA also had the t-PA inhibitor and were at greater risk for earlier and more severe disease than were allografts with normal arteriolar t-PA levels. Twelve patients whose allografts were depleted of t-PA either received a second transplant or died, whereas only one of the patients whose allografts had persistently normal t-PA levels died (P < 0.001). CONCLUSIONS: These findings reveal an association between the depletion of t-PA from arteriolar smooth-muscle cells and the subsequent development of coronary artery disease and decreased graft survival. Although we cannot be certain about a cause-and-effect relation, our data suggest a possible role for deficient fibrinolysis in the development of coronary artery disease in transplanted human hearts.

Coronary Angiography↗
PubMed1995

alpha-Glutathione S-transferase as a marker of hepatocellular damage in chronic hepatitis C virus infection.

alpha-Glutathione S-transferase (alpha GST) may be a good serologic marker of hepatocellular damage because of its low molecular weight, uniform hepatic distribution, high cytosolic concentration, and short half-life. To determine the clinical utility of alpha GST in patients with chronic hepatitis C virus (HCV) infection, serum alpha GST levels were measured in 96 patients with chronic HCV infection, of whom 47 subsequently underwent interferon-alpha therapy. Patients were simultaneously evaluated with conventional liver biochemistry, serum HCV RNA levels, and liver histology. Different methods of serum collection did not affect alpha GST values, indicating that this was a stable serum marker. In 93% of patients with chronic HCV infection, alpha GST was elevated and showed an excellent correlation with serum aminotransferases. Histologic analysis revealed a correlation of alpha GST with both lobular inflammation and bile duct lesions. There was no correlation between serum alpha GST levels and the demographic features, mode of transmission, virologic, other histologic parameters, or subsequent response to interferon-alpha. During serial monitoring in patients undergoing interferon-alpha therapy, elevation of serum alpha GST correlated with biochemical relapse and in some patients virologic relapse in the presence of normal liver biochemistry. alpha GST was persistently elevated in all nonresponders. Four of six of those patients who responded completely followed by early relapse had elevated alpha GST intermittently or continuously during therapy despite normalization of serum aminotransferases. Two of five of those with a complete and sustained response had elevated alpha GST during treatment and follow-up, and both were also seropositive for HCV RNA during follow-up. These data demonstrate that alpha GST is a stable marker, has similar diagnostic utility as serum aminotransferases, and may have a role in the monitoring of patients undergoing interferon-alpha therapy.

Adult↗
PubMed1995

The effects of roasting temperature applied to whole soybeans on site of digestion by steers: II. Protein and amino acid digestion.

A 4 x 5 Youden square design was used to determine the effect of roasting temperature of whole soybeans on escape of CP from the rumen and disappearance of N from the small intestine in steers. Four steers (average BW 373 kg +/- 30.7) cannulated at the rumen, duodenum, and ileum were fed each of five diets (1.8% of BW) over five periods. The basal diet contained corn silage (50% of diet DM), alfalfa hay (24%), corn-urea premix (6%), corn starch grits (16.6%), and soybean oil (3.4%). Soybeans (16% of diet DM), either raw or heated to an exit temperature of 141, 149, or 157 degrees C in a commercial roaster, replaced the soybean oil and most of the corn starch grits in the soybean-containing diets. Ruminal ammonia N was lower (P < .05) for the basal diet than for the soybean-containing diets. Roasting temperature of whole soybeans had no significant impact on ruminal ammonia N. Total N reaching the duodenum was greater (P < .05) for steers fed the soybean diets than for steers fed the basal diet. Non-bacterial N (dietary N) at the duodenum was increased (P < .05) by feeding soybeans. Soybean N reaching the duodenum decreased with increased roasting temperature. Increased roasting temperature of whole soybeans seemed to make the soybeans more brittle, subsequently increasing degradation of CP in the rumen. However, disappearance of soybean N in the small intestine, as a proportion of the soybean N entering the small intestine, increased with increased roasting temperature. Apparent total tract N digestibility was increased (P < .05) by feeding soybeans. Flow to the duodenum and small intestinal digestibility of total, essential, and nonessential amino acids increased (P < .05) when soybeans were fed and when roasted vs raw soybeans were fed. Under normal roasting conditions, it seemed that little potential for heat damage to the soybean protein existed. Instead, undesirable effects of heating on handling characteristics of the soybeans were reached before the point at which loss of nutritive value occurred. Feeding steers diets containing roasted whole soybeans increased the N and amino acids available to steers over steers fed diets containing raw soybeans due to increased ruminal soybean nitrogen escape and increased small intestinal digestibility.

Amino Acids↗
PubMed1992

Pharmacokinetics of metoclopramide in goats.

The pharmacokinetics of a parenteral formulation of metoclopramide (monochloride monohydrate) were determined following single intravenous (i.v.) and intramuscular (i.m.) 0.5-mg/kg doses to two groups of 4 goats in a crossover design. Mean serum concentrations of metoclopramide following i.v. administration of 0.5 mg/kg declined rapidly from a peak of 277.5 ng/ml at 3 min post-dosing to 25 ng/ml at 90 min. Serum concentrations were not detectable by 120 min after drug administration. The curve of serum concentrations vs. time was characteristic of a two-compartment open model. Mean parameters from analysis of the individual i.v. data gave a biological half-life of 0.62 h and a volume of distribution of the central compartment of 1.34 l/kg. Serum concentrations of metoclopramide following i.m. administration of 0.5 mg/kg rose rapidly to a peak of 160.9 ng/ml at 15 min post-dosing and then declined in parallel with the elimination phase of the i.v. study. These data were best described by a two-compartment open model with first-order absorption. The mean biological half-life was 1.04 h. There were no adverse reactions associated with metoclopramide at the 0.5-mg/kg dose administered by either route.

Absorption↗
PubMed1992

Identification of the homozygous recessive genotype for the deficiency of uridine monophosphate synthase in 35-day bovine embryos.

Holstein-Friesian cattle heterozygous for the deficiency of uridine monophosphate (UMP) synthase have half-normal activity of UMP synthase. The homozygous recessive genotype would result in little or no activity, has not been observed among live animals and apparently leads to embryonic mortality at approximately Day 40 of gestation. Activity of UMP synthase averaged 2.74 +/- 0.61 units/mg protein for 19 obligatory normal embryos (from normal x normal matings). Activity for 18 embryos from heterozygote x heterozygote matings yielded three non-overlapping groups as follows: (i) five presumed normals with greater than two-thirds normal activity, (ii) ten apparent heterozygotes with one-third to two-thirds normal activity and (iii) three putative homozygous recessive embryos with less than one-third normal activity. The distribution among these groups was consistent with the 1:2:1 ratio expected for autosomal inheritance. Conception of embryos homozygous recessive for this disorder was demonstrated.

Animals↗
PubMed1991

Effect of tissue adhesives and suture patterns on experimentally induced teat lacerations in lactating dairy cattle.

Tissue adhesives and suture materials were evaluated for repair of experimentally induced teat lacerations in 6 lactating dairy cows. Group-1 teat lacerations were not closed and served as nonsutured controls. Group-2 lacerations were closed in three layers (mucosa, submucosa, and skin) by use of 3-0 polydioxanone. Group-3 lacerations were closed by use of N-butyl cyanoacrylate monomer tissue adhesive. Group-4 lacerations were closed by use of a combination of sutures and tissue adhesive. All cows were milked by machine. Healing was observed for 28 days, then cows were slaughtered, and teats were recovered for further study. Evaluation revealed failure of healing of all layers with formation of large fistulas in 3 of 4 nonsutured control teats in group 1. All 6 teat lacerations in groups 2 and 3 healed satisfactorily with no fistulas. Five of 6 teats in group 4 had partial healing of skin and mucosa with no fistulas, and 1 teat failed to heal and developed a small fistula. Data indicated that closure of experimentally induced teat lacerations with three layers of fine absorbable suture or closure with tissue adhesive alone gave good results and satisfactory healing of all layers. However, when sutures and tissue adhesive were used together, foreign body reaction was marked, and the skin and submucosa healed only partially. Sutures appeared to entrap the tissue adhesive, resulting in a foreign body reaction.

Animals↗
PubMed1991

Effect of paroxetine, a selective 5-hydroxytryptamine uptake inhibitor, on beta-adrenoceptors in rat brain: autoradiographic and functional studies.

Quantitative receptor autoradiography was used to investigate the effects of paroxetine (8.3 mg/kg), amitriptyline (26 mg/kg) and desipramine (17 mg/kg), administered daily in the drinking water for 21 days, on the number of beta 1- and beta 2-adrenoceptors in the cortex of the rat. In addition, the effect of these drugs on the function of beta-adrenoceptors was examined by measuring noradrenaline- and isoprenaline-stimulated production of cyclic AMP in slices of cortex. Paroxetine did not alter the number of cortical beta 1 or beta 2-adrenoceptors nor did it induce any functional changes in beta-adrenoceptor-linked adenylyl cyclase. In contrast, desipramine caused a significant reduction in the density of beta 1-adrenoceptors and in the sensitivity of both noradrenaline and isoprenaline-stimulated adenylyl cyclase. Although amitriptyline significantly reduced the number of beta 1-adrenoceptors in cortical membranes, no such changes could be detected by autoradiography. It is apparent from these and other studies, that the ability of antidepressants to down-regulate central beta-adrenoceptors is not a property shared by all antidepressants. In particular, the more potent and selective inhibitors of the uptake of 5-HT, such as paroxetine, appear to be devoid of effects on this receptor system.

Adrenergic beta-Antagonists↗
PubMed1991

The UDP glucuronosyltransferase gene superfamily: suggested nomenclature based on evolutionary divergence.

A nomenclature system for the UDP glucuronosyltransferase superfamily is proposed, based on divergent evolution of the genes. A total of 26 distinct cDNAs in five mammalian species have been sequenced to date. Comparison of the deduced amino acid sequences leads to the definition of two families and a total of three subfamilies. For naming each gene, we propose that the root symbol UGT for human (Ugt for mouse), representing "UDP glucuronosyltransferase," be followed by an Arabic number denoting the family, a letter designating the subfamily, and an Arabic numeral representing the individual gene within the family or subfamily (hyphen before the Arabic number for mouse), e.g., human UGT2B1 and murine Ugt2b-1. Whereas the gene and cDNA should be italicized, the corresponding transcript, protein, and enzyme activity should not be written with lowercase letters or in italics, e.g., human or murine UGT2B1. Recent experimental evidence suggests that several exons of the UGT1 gene might be shared, indicating that distinct UGT1 transcripts and proteins may arise via alternative splicing; the gene and gene product of alternative splicing will be designated with an asterisk, e.g., UGT1*6 and UGT1*6, respectively. When an orthologous gene between species cannot be identified with certainty, as occurs in the UGT2B subfamily, we recommend sequential naming of the genes chronologically as they become characterized. We suggest that the human nomenclature system be used for species other than the mouse. We anticipate that this UGT gene nomenclature system will require updating on a regular basis.

Animals↗
PubMed1991

Effects of urea and starch on rumen fermentation, nutrient passage to the duodenum, and performance of cows.

Four midlactation, multiparous Holstein cows fitted with ruminal and duodenal cannulas were used in a 4 x 4 Latin square design to determine the effects of supplementing urea or starch or both to diets containing fish meal on passage of nutrients to the small intestine and performance of lactating cows. The treatments (in a 2 x 2 factorial arrangement) were 1) control and control plus 2) urea, 3) starch, or 4) starch and urea. Supplementing diets with urea did not affect DMI; ruminal, postruminal, or total tract digestibilities of DM, starch, ADF, or NDF; ruminal fluid VFA concentrations or molar percentages; or ruminal fluid or particulate dilution rates. Feeding additional starch depressed DMI but did not alter ruminal or postruminal digestion of OM or VFA concentrations and molar percentages in ruminal fluid. Ruminal fluid ammonia concentration was increased by feeding urea and decreased by feeding additional starch. Passage of nonammonia N, nonammonia nonmicrobial N, or microbial N to the small intestine and efficiency of microbial CP synthesis were not affected significantly by supplying either urea or additional starch. Feeding urea increased passage of methionine to the small intestine, whereas feeding additional starch increased passage of methionine and arginine. Passage of other amino acids to the small intestine was not altered significantly by feeding urea or additional starch. Production of milk and milk protein was increased, but yields of fat and SNF were not altered by feeding diets supplemented with urea. Production of milk and milk fat was not affected, but yields of CP and SNF were decreased when additional starch was fed to cows.

Ammonia↗
PubMed1991

Effects of calcium salts of fatty acids and protein source on ruminal fermentation and nutrient flow to duodenum of cows.

Four Holstein cows fitted with ruminal and duodenal cannulas were used in a 4 x 4 Latin square to investigate the effects of calcium salts of long-chain fatty acids (fat) and source of protein (fish meal or soybean meal) on ruminal fermentation, flow of nutrients to the small intestine, and animal performance. Cows were fed for ad libitum intake a diet of 30% alfalfa haylage, 20% corn silage, and 50% concentrate on a DM basis. Treatments, arranged in a 2 x 2 (fat x protein) factorial, were 1) soybean meal, no fat; 2) soybean meal, fat; 3) fish meal, no fat; and 4) fish meal, fat. Intake of DM was not affected by fat or protein source, but feeding fat decreased the amount of OM truly digested in the rumen. Starch intake was decreased, but flow of starch to the duodenum was not altered by feeding fat. Nonammonia N and microbial N flows to the duodenum were not affected by treatment comparisons. However, efficiency of microbial growth was increased by feeding fat, but not by source of protein. Passage of amino acids to the duodenum was not affected by source of protein, probably because fish meal contributed only 17% of the total dietary CP, and microbial N constituted about 50% of the NAN passing to the duodenum; this had an equalizing effect on the pattern and quantity of amino acids that passed to the duodenum. Feeding fat or different sources of protein did not alter milk production. Milk fat percentage was increased, and protein percentage was decreased when fat was fed, but yields of milk fat and protein were not different.

Amino Acids↗
PubMed1991

Effects of calcium salts of fatty acids and proportion of forage in diet on ruminal fermentation and nutrient flow to duodenum of cows.

Four Holstein cows fitted with ruminal and duodenal cannulas were used in a 4 x 4 Latin square to investigate the effects of calcium salts of long-chain fatty acids (fat) and proportion of forage in diet on ruminal fermentation, flow of nutrients to the small intestine, and animal performance. Treatments, arranged in a 2 x 2 (fat x forage) factorial, were 1) low (50%) forage, no fat; 2) low forage, fat; 3) high (67%) forage, no fat; and 4) high forage, fat. Feeding fat decreased OM intake and OM truly digested in the rumen. Feeding high forage diets decreased intakes of OM and starch and increased intakes of ADF and NDF. Ruminal pH and ratio of acetate to propionate were increased with high forage diets compared with low forage diets. Feeding fat and different amounts of forage to cows did not alter the flows of NAN and microbial N to the duodenum or efficiency of microbial growth. Production of milk and 4% FCM and percentage of fat in milk were increased by feeding fat. Feeding high forage diets decreased milk production, increased percentage of fat in milk, increased the yield of fat, and caused no change in 4% FCM production. The percentage of protein in milk was decreased by feeding high forage diets and fat, but yield of milk protein was decreased only by feeding high forage diets to cows.

Amino Acids↗
PubMed1991

Effects of somatotropin and duodenal infusion of amino acids on nutrient passage to duodenum and performance of dairy cows.

Four multiparous Holstein cows were used in a 4 x 4 Latin square to investigate the effects of bST and postruminal infusion of lysine and methionine on ruminal fermentation, flow of nutrients to the small intestine, and animal performance. The treatments were 1) control; 2) control plus 24 g of lysine and 8 g of methionine/d; 3) control plus 25 mg of bST/d; and 4) control plus 25 mg of bST/d plus 24 g of lysine and 8 g of methionine/d. Intakes of DM, OM, CP, starch, NDF, and ADF were similar among treatments. Ruminal characteristics, flow of nutrients to the small intestine, and total tract apparent digestibilities of nutrients were not affected by injection of bST or postruminal infusion of lysine and methionine in this short-term experiment. Milk production, 4% FCM, milk fat percentage and yield, and production of milk CP were increased by administering bST. Postruminal infusion of lysine and methionine did not affect milk production or composition.

Ammonia↗
PubMed1991

Laboratory investigation of deaths due to anaphylaxis.

To establish a useful laboratory protocol to investigate possible cases of fatal anaphylaxis, we measured mast-cell-derived tryptase levels and allergen-specific immunoglobulin E (IgE) antibody levels in sera obtained prior to or within 24 h after death from 19 anaphylaxis victims. Elevated serum tryptase levels (range = 12 ng/mL to 150 micrograms/mL) were found in nine of nine Hymenoptera sting fatalities, six of eight food-induced fatalities, and two of two reactions to diagnostic therapeutic agents. Tryptase levels were normal (less than 10 ng/mL) in 57 sequential sera obtained postmortem from six control patients. Tryptase could not be measured in pleural or pericardial fluids for technical reasons. Serum IgE antibodies were elevated in five of the nine Hymenoptera sting fatalities and in eight of the eight fatal food reactions; assays were unavailable for the two diagnostic/therapeutic agents. If elevated, the victim's serum IgE antibodies to food could be used to identify allergens in uneaten portions of foods consumed shortly before the anaphylactic event. IgE antibodies were moderately stable during storage in a variety of anticoagulants at room temperature for up to 11 weeks. Elevated mast-cell-derived tryptase levels in postmortem sera reflect antemortem mast cell activation and may be used as a marker for fatal anaphylaxis. If assays are available for IgE antibodies to relevant allergens, such assays provide evidence for antemortem sensitization; these assays may be modified to identify allergens in foods consumed by victims of food-induced anaphylaxis.

Aged↗
PubMed1990

Surgical repair of peripheral detachment of the medial meniscus in 34 cattle.

A detachment of the periphery of the medial meniscus from the joint capsule and medial collateral ligament in 34 cattle was repaired by securing the meniscus to the joint capsule with vertical mattress sutures during arthrotomy. Of 28 cattle with follow-up reports, 20 had recovered satisfactorily by their owners' evaluations; 17 were either not lame or slightly lame after the operation and three were moderately lame. Three of four cattle without follow-up reports were either not lame or slightly lame when discharged from the hospital.

Animals↗