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Biomedical subjects

D R Nelson

Publications and source records attributed to D R Nelson.

At least 163 records · Page 9Linked to original sources

Effect of prolonged 5-hydroxytryptamine uptake inhibition by paroxetine on cortical beta 1 and beta 2-adrenoceptors in rat brain.

The effects of prolonged (21 day) oral administration of the antidepressants paroxetine (0.9 to 8.9 mg/kg/day) and amitriptyline (2.7 to 27 mg/kg/day), on rat brain cortical beta 1- and beta 2-adrenoceptor numbers and affinities were investigated using [3H]-CGP 12177. Although amitriptyline, 27 mg/kg, caused a significant (p less than 0.05) 20% reduction in the number of beta 1-adrenoceptors, paroxetine, at doses up to 8.9 mg/kg p.o., did not influence binding of [3H]-CGP 12177 to cortical beta 1- or beta 2-adrenoceptors. This study with paroxetine provides further evidence that the down-regulation of central beta 1-adrenoceptors in rat brain after repeated administration is not a property of all antidepressant drugs.

Adrenergic beta-Antagonists↗

Lack of suppression of IgE production by recombinant interferon gamma: a controlled trial in patients with allergic rhinitis.

Recent evidence suggests that interferon-gamma (IFN-gamma) is a potent inhibitor of IgE synthesis in rodents. We conducted a randomized, placebo-controlled, two-period clinical trial of human recombinant IFN-gamma in the treatment of allergic rhinitis. Forty-five adults with well-documented ragweed-allergic rhinitis were randomized into three groups of 15 adults each and received subcutaneous injections three times weekly. The first treatment period (4 weeks during the off season) began on April 18, 1988; the second treatment period (6 weeks during ragweed pollination) began on August 15, 1988. All subjects received the same treatment in both periods. Group 1 received 0.2 mg per injection of IFN, group 2 received 0.02 mg of IFN, and group 3 received placebo. One subject in group 1 and three subjects in group 2 withdrew because of adverse reactions, and three subjects withdrew for personal reasons. There were no significant differences in mean weekly symptom scores or supplemental medication scores among the three groups in either treatment period. Furthermore, there were no significant differences in the changes of serum IgE antibody to crude ragweed extract or in serum total IgE among the three groups during or before the ragweed-pollination season. These results indicate that this treatment regimen with IFN-gamma does not alter IgE production in patients with ragweed hay fever and indicate the need for further clinical research of lymphokine modulation of IgE production.

Adolescent↗

Biochemical and immunochemical comparison of Africanized and European honeybee venoms.

Africanized honeybees (HBs) pose a hazard to both normal and sting-sensitive subjects in certain areas of Central and South America, and it is predicted that they will soon be present in the southern United States as well. Using an electrical stimulation device, we collected Africanized HB venom (AHV) in Venezuela and European HB venom (EHV) in Louisiana. These venoms, along with commercial European HB venom (CHV), were compared by thin-layer isoelectric focusing and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The Coomassie brilliant blue and silver-stained banding patterns of AHV and EHV were essentially identical to CHV. Western blots were prepared from SDS-PAGE gels and tested with pooled sera from EHV-sensitive subjects and then radiolabeled antihuman IgE. The resulting autoradiographs revealed similar banding patterns among EHV, AHV, and CHV. RAST-inhibition studies were performed with solid-phase CHV and pooled sera from EHV-sensitive subjects. The specific allergenic activities of the three HB venoms (allergy units per milligram of protein) were comparable. By RAST-inhibition assay with solid-phase, highly purified individual venom components, AHV and EHV both contained phospholipase A2, hyaluronidase, and high-molecular-weight allergens. The increased morbidity after Africanized HB stings is likely related to their more defensive behavior during which many bees react by stinging rather than to biochemical or allergenic differences between AHV and EHV.

Allergens↗

Characterization of the heat shock response and identification of heat shock protein antigens of Borrelia burgdorferi.

The heat shock response of Borrelia burgdorferi B31 cells was characterized with regard to the heat shock proteins (Hsps) produced. Five to seven Hsps were detected by sodium dodecyl sulfate-gel electrophoresis and fluorography of proteins from cells labeled with [35S]methionine after shifts from 33 degrees C to 37 or 40 degrees C or from 20 degrees C to 33, 37, or 40 degrees C. Analysis of [35S]methionine-labeled Hsps by two-dimensional electrophoresis and autoradiography revealed 12 Hsps. Western immunoblot analysis with antisera to highly conserved Escherichia coli and Mycobacterium tuberculosis Hsps revealed a single 72-kilodalton (kDa) protein band that reacted with antibodies to E. coli DnaK and with antibodies to the M. tuberculosis 71-kDa Hsp homolog of E. coli DnaK. Two proteins with apparent molecular masses of 66 and 60 kDa reacted with antibodies against the M. tuberculosis 65-kDa Hsp homolog of E. coli GroEL. Human immune sera collected from patients with Lyme disease reacted with both the 66-kDa Hsp and the 60-kDa Hsp but failed to react with the 72-kDa Hsp. These data are discussed with regard to the possibility that host recognition of highly conserved epitopes of GroEL homologs of B. burgdorferi may result in autoimmune reactions causing arthritis and other pathologies.

Bacterial Proteins↗

Effect of energy level and feeding frequency on site of digestion and postruminal nutrient flows in steers.

Four cannulated (rumen, proximal duodenum, terminal ileum) Simmental steers were fed ground corn and corn silage (low forage) or alfalfa hay and corn silage (high forage) diets twice or 12 times daily to examine effects of energy level and feeding frequency on nutrient digestion. Site of organic matter digestion was shifted from the rumen to the small intestine, and total tract organic matter digestion was increased when steers were fed the low forage diet. Although intakes and flows at all sites within the tract of NDF and ADF were greater when the high forage diet was fed, digestion of these components (percentage total tract digestion) within respective sites was unaffected by energy level. Nonbacterial N flows at the duodenum increased when steers were fed the low forage diet and when fed 12 times daily. Total amino acid flows at the duodenum tended to be increased when steers were fed the low forage diet. Results suggest that dietary energy level can impact on site of nutrient digestion and supply of nutrients at different sites within the digestive tract. However, feeding frequency had minimal effect on site or extent of nutrient digestion. The lack of interaction between energy level and feeding frequency in this experiment may be related to the level of DM intake and nature of the diets fed.

Animal Feed↗

Effects of source and amount of protein on ruminal fermentation and passage of nutrients to the small intestine of lactating cows.

Four Holstein cows fitted with ruminal and duodenal cannulas were used in a 4 x 4 Latin square to investigate the effects of source (corn gluten meal or soybean meal) and amount (14.5 or 11.0%) of CP on ruminal fermentation, passage of nutrients to the small intestine, and animal performance. Cows wee fed for ad libitum intake a diet of 60% corn silage and 40% concentrate on a DM basis. The treatments, arranged in a 2 x 2 (source x amount of CP) factorial, were 1) 14.5% CP, soybean meal; 2) 11.0% CP, soybean meal; 3) 14.5% CP, corn gluten meal; and 4) 11.0% CP, corn gluten meal. Digestion in the rumen of OM, starch, ADF, and NDF was not affected by source or amount of CP in the diet. Total VFA and NH3 concentrations in ruminal fluid were increased by feeding diets that contained 14.5% CP or soybean meal. FLows of non-NH3 N and amino acids to the duodenum were greater in cows fed the 14.5% CP diets because of a greater flow of non-NH3 nonmicrobial N to the duodenum. Larger amounts of lysine passed to the duodenum when cows were fed soybean meal compared with corn gluten meal. Microbial N flow to the duodenum and efficiency of microbial growth were not affected by treatments, suggesting that ruminal NH3 concentration was not limiting for maximal microbial protein synthesis. Feeding 14.5% CP diets increased the production of milk (29.5 vs. 26.8 kg/d) and milk protein compared with 11.0% CP diets, possibly because of greater passage of amino acids to the small intestine. Feeding soybean meal to cows increased production of milk protein compared with feeding corn gluten meal, possibly because more lysine passed to the small intestine.

Amino Acids↗

The promotional effect of bone wax on experimental Staphylococcus aureus osteomyelitis.

The consequences of using surgical bone wax are not well studied. We evaluated the infection-promoting potential of sterile bone wax in a rat model of chronic Staphylococcus aureus osteomyelitis. The addition of bone wax greatly reduced the quantitative bacterial inoculum (log colony-forming units) required to establish chronic osteomyelitis in 50% and 100% of challenged animals. The 50% infection rate was reduced from log 6.9 to 2.6 and the 100% infection rate from 8.2 to 4.4, respectively (p less than 0.015, t test for parallelism). Separate experiments were done 10 to 30 minutes after inoculation with only log 6.4 staphylococci. Tibiae of animals that received bone wax yielded more organisms than those that did not (log 2.76 +/- 0.68 versus 1.72 +/- 0.94, p less than 0.01). At 24 hours quantitative colony counts were not significantly different whether animals received wax or not (log 5.02 +/- 0.42 versus 4.43 +/- 0.65, p greater than 0.09). These studies suggest that the routine surgical use of bone wax should be reassessed.

Animals↗

Secondary structure prediction of 52 membrane-bound cytochromes P450 shows a strong structural similarity to P450cam.

The secondary structure of 52 aligned cytochrome P450 sequences, all of which are membrane bound, is predicted and collectively compared with the crystal structure of the soluble cytochrome P450cam. Ten of 13 helical regions, 6 of 7 beta-pair regions, and beta-structure corresponding to a known beta-bulge near the active site of P450cam are predicted to exist in the membrane-bound P450s. Three turns associated with beta-structure in the soluble enzyme are also predicted for the membrane-bound forms. A strong structural similarity is evident between membrane P450s and the soluble P450cam. Consequently, a multitransmembrane structure involving much of P450 seems highly unlikely. A structure with two N-terminal transmembrane segments is compatible with these observations.

Animals↗

Selective and functional 5-hydroxytryptamine3 receptor antagonism by BRL 43694 (granisetron).

The activity of BRL 43694 (granisetron) was investigated using established models of 5-HT3 receptor activity. In guinea-pig isolated ileum, BRL 43694 antagonised the contractions evoked by relatively high concentrations of 5-HT (pA2 = 8.1 +/- 0.2). However, except in high concentrations, BRL 43694 did not affect the contractions of similar preparations of ileum, evoked by electrical field stimulation (cholinergically mediated), the nicotinic agonist dimethylphenyl piperazinium (DMPP) or by cholecystokinin octapeptide. Similarly, BRL 43694 did not affect electrically evoked, cholinergically mediated contractions of rat or human isolated stomach. In other models of 5-HT3 receptor activity (rabbit isolated heart, Bezold-Jarisch reflex in anaesthetised rats), potent antagonism by BRL 43694 was demonstrated. In radioligand binding studies on rat brain membranes, BRL 43694 had little or no affinity for 5-HT1A, 5-HT1B, 5-HT2 or for many other binding sites. BRL 43694 may therefore be a potent and selective 5-HT3 receptor antagonist.

Acetylcysteine↗

Treatment of chronic experimental Staphylococcus aureus osteomyelitis with LY146032 and vancomycin.

LY146032 and vancomycin were compared as therapeutic agents in the treatment of chronic Staphylococcus aureus osteomyelitis in the rat. Quantitative cultures disclosed that one of 16, none of 16 and two of 17 tibiae were sterile from the control LY146032, and vancomycin groups, respectively. From positive cultures, geometric mean staphylococcal CFU per gram of bone were as follows: control, 5.13 +/- 1.58; LY146032, 5.36 +/- 0.43 (p = 0.57); and vancomycin, 4.33 +/- 1.73 (p = 0.078). Mean gross pathology was decreased significantly in both treatment groups. LY146032 was no more effective than vancomycin in reducing bacterial counts.

Animals↗

Approaches to acute asthma and status asthmaticus in children.

Asthma is the most common chronic disease in pediatric patients and is the leading cause of childhood disability. The functional abnormalities of this disease--namely, airway obstruction and hyperresponsiveness--are consequences primarily of airway inflammation. Outpatient therapy for acute asthma, as well as therapy for status asthmaticus (episodes of asthma unresponsive to usually effective outpatient therapy and necessitating hospitalization), primarily addresses treatment of airway inflammation. The goal of office and emergency room management of acute asthma is reversal of airway obstruction by the administration of inhaled beta-adrenergic medications. The therapy for status asthmaticus consists of intravenously administered aminophylline, corticosteroids, nebulized beta-adrenergic agents, and oxygen. Respiratory failure, the inability to maintain adequate elimination of CO2, may be effectively treated by adding continuous nebulization of albuterol. Mechanical ventilation will still be necessary in the rare patient who does not respond to pharmacologic therapy. Acute exacerbations of asthma, as well as status asthmaticus, can best be prevented by establishing effective maintenance programs individualized for each patient.

Adolescent↗

Evolution of the cytochrome P450 genes.

1. The P450 gene superfamily is presently known to contain more than 78 members, divided into 14 families. 2. The superfamily has undergone divergent evolution, and the ancestral gene is probably more than 2 billion years old. 3. The recent 'burst' in new P450 genes, particularly in the II family during the past 800 million years, appears to be the result of 'animal-plant warfare'. 4. Due to the presence or absence of a particular P450 gene in one species but not the other, it may not be correct to extrapolate toxicity or cancer data from rodent to human. 5. Increases in the P450 gene product (enzyme induction) almost always reflect an elevated rate in gene transcription, although there are several exceptions. 6. The mechanisms of P450 gene regulation (induction) by classes of inducers might become better understood through the comparison of different phyla that differ in response to a particular class of inducers. 7. Amongst several carefully selected phyla, delineation between which electron donor (presence of Fe2S2 protein or NADPH-P450 oxidoreductase, or both) interacts with P450 may provide valuable information about the evolution of eukaryotes from prokaryotes.

Animals↗

Effects of source of protein and carbohydrate on ruminal fermentation and passage of nutrients to the small intestine of lactating cows.

Four early lactation multiparous Holstein cows were used in a 4 x 4 Latin square to investigate the effects of source of protein (fish meal or soybean meal) and carbohydrate (corn or barley) on ruminal fermentation, flow of nutrients to the small intestine, and animal performance. The treatments, arranged in a 2 x 2 (protein x carbohydrate) factorial were: 1) corn plus soybean meal; 2) corn plus fish meal; 3) barley plus soybean meal; and 4) barley plus fish meal. Dry matter and starch intakes were greater when corn was fed than when barley was fed. Barley-based diets were more extensively degraded in the rumen than corn-based diets and therefore provided more energy for microbial growth. However, passage of amino acids and starch to the duodenum was greater for corn-based diets than barley-based diets, because of the greater intake and lower ruminal degradability of the corn-based diets. Microbial protein constituted a larger portion of the total N and had a greater influence on the pattern and quantity of amino acids that passed to the duodenum than did protein from fish meal or soybean meal, which escaped ruminal degradation. Feeding corn-based diets increased production of milk and milk protein compared with feeding barley-based diets.

Animals↗