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Biomedical subjects

L A Nelson

Publications and source records attributed to L A Nelson.

At least 37 records · Page 2Linked to original sources
PubMed1989

Synthesis and cytotoxic activity of pyridylthio, pyridylsulfinyl, and pyridylsulfonyl methyl acrylates.

Nineteen 2-pyridylthio (2), 2-pyridylsulfinyl (3) or 2-pyridylsulfonyl (4) derivatives of (Z)-methyl acrylate were synthesized in order to investigate the effect of the oxidation state of the sulfur atom, and the position and nature of pyridyl substituents on cytotoxic activity. Analogous sulfinyl and sulphonyl derivatives were equipotent, and more potent than analogous thio derivatives, in an vitro L1210 screen. In most cases, incorporation of nuclear trifluoromethyl and chloro substituents at various positions of the pyridyl ring of the sulfinyl derivatives (compounds 3b-3h) decreased activity relative to the unsubstituted sulfinyl 3a (ED50 0.43 micrograms/ml). Compounds 3b, 3d and 3i exhibited weak antineoplastic activity in an in vivo P388 screen at a dose of 5 mg/kg.

Animals↗
PubMed1988

Effects of glucose infusion in exercising rats.

To determine whether feedforward control of liver glycogenolysis during exercise is subject to negative feedback by elevated blood glucose, glucose was infused into exercising rats at a rate that elevated blood glucose greater than 10 mM. Liver glycogen content decreased 22.4 mg/g in saline-infused rats compared with 13.6 mg/g in glucose-infused rats during the first 40 min of treadmill running (21 m/min, 15% grade). Liver adenosine 3',5'-cyclic monophosphate (cAMP) concentration was significantly lower in the glucose-infused rats during the exercise bout. The concentration of hepatic fructose 2,6-bisphosphate remained elevated throughout the exercise bout in glucose-infused rats but decreased markedly in saline-infused rats. Plasma insulin concentration was higher and plasma glucagon concentration lower in glucose-infused rats than in saline-infused rats during exercise. Early in exercise, liver glycogenolysis proceeds in the glucose-infused rats despite the fact that glucose and insulin concentrations are markedly elevated and liver cAMP is unchanged from resting values. These observations suggest the existence of a cAMP-independent feedforward system for activation of liver glycogenolysis that can override classical negative feedback mechanisms during exercise.

Animals↗
PubMed1988

Exaggerated atrial natriuretic peptide release during acute exercise in essential hypertension.

The effects of acute exercise on plasma concentrations of atrial natriuretic peptide (ANP), arginine vasopressin (AVP), and plasma renin activity (PRA) were studied in 13 patients with previously untreated essential hypertension, and 8 matched normotensive control subjects. Resting levels of ANP and PRA were similar in the two groups, while resting AVP concentrations were 1.4 times higher in hypertensive subjects. Graded exercise was performed on a bicycle ergometer with workload increased each minute until exhaustion (Wmax). Wmax was higher in normal subjects than in hypertensive patients. Blood pressure and heart rate rose more steeply in hypertensive patients. Plasma ANP increased during acute exercise in both groups, but the average increase in hypertensives was substantially greater than in normal subjects (P less than 0.05). The increase in ANP during exercise was greater in hypertensives with left ventricular (LV) hypertrophy, and there was a positive correlation between LV mass and the percentage rise in ANP during exercise (r = 0.56, P less than 0.005). Plasma AVP did not alter during exercise. Plasma renin concentrations showed a small rise during exercise in both groups, which was 16% less in hypertensive subjects (P less than 0.05). The enhancement of ANP release during exercise in hypertensive subjects may reflect both cardiac structural changes and increased redistribution of blood to the cardiopulmonary compartment.

Arginine Vasopressin↗
PubMed1987

Human leukemia cell binding and killing by anti-CD5 radioimmunotoxins.

We have synthesized a reagent for antibody directed cell targeting composed of the monoclonal antibody (MoAb) T101 linked to the potent toxin ricin. The immunotoxin (IT) was subsequently radiolabeled by a cyclic anhydride procedure with 90Yttrium (90Y) to construct a radioimmunotoxin (RIT) that may have potential for cancer therapy. We evaluated the reagent for selectivity in binding and protein synthesis inhibition (PSI) assays. The RIT selectively bound antigen positive leukemia T-cell lines, with minimal binding to antigen negative control lines. The IT inhibited 87% or greater protein synthesis activity at 1 microgram/ml and exhibited an IC50 (the dose inhibiting 50% activity) of 0.18 +/- 0.08 microgram/ml in the presence of lactose. RIT and nonlabeled IT showed comparable degrees of PSI at 1 microgram/ml and 10 micrograms/ml, suggesting that labeling had little overall effect on the activity of the immunoconjugate. However, indirect evidence showed that the galactose binding site of ricin was inhibited 10-fold by its exposure to 90Y. Control RIT were minimally inhibitory. IT labeled with 131Iodine (131I) by an iodine monochloride technique also retained its capability to selectively inhibit protein synthesis. When RIT were tested for potency in a clonogenic assay against human leukemia T-cell lines, they inhibited 3.61 logs of tumor cell growth at 10 micrograms/ml. This did not represent an improvement over the log elimination with radiolabeled antibody alone, which showed 4.19 log elimination of tumor cells. Our observation that the 90Y-labeled RIT and labeled antibody can selectively eliminate about four logs of tumor cells in an in vitro clonogenic assay is unique. The ability of RIT to kill several logs of tumor cells in vitro renders RIT interesting anti-tumor reagents.

Antibodies, Monoclonal↗
PubMed1987

Interaction of dietary protein level on dose response relationships during aflatoxicosis in young chickens.

It is well known that the effect of aflatoxin is enhanced by a low protein diet, but whether this is associated with a lower apparent minimum effective dose, increased slope of response curves, or both has not been investigated previously. Aflatoxin at 12 dosages ranging from 0 to 2.34 micrograms/g of feed was fed to eight groups of 10 young chickens per treatment consuming a 10.00 or 12.75% protein diet for 3 weeks. The body weights, liver weights relative to body weights, and total lipid content of the livers were determined. Mathematical models were fitted to the data and from the appropriate equations the dose-response curves were predicted as continuous functions of aflatoxin concentration. A quadratic polynomial fit body weight data on the 12.75% protein diet whereas a plateau-linear model fit body weight data on the 10.00% protein diet. This implies that in a low protein diet aflatoxin affects only one of the factors controlling growth. Plateau-linear models fit liver relative weight and liver lipid content data on both 10.00 and 12.75% diets. For both variables the lower protein diet decreased the apparent minimum effective dose and increased the positive slope of the linear response. The apparent minimum effective doses (micrograms of aflatoxin per gram of feed) in this experimental system were calculated from the modeling approach to be 1.21 and 2.00 for body weight, 1.08 and 1.65 for liver lipids, and 1.45 and 2.34 for liver relative weight in 10.00 and 12.75% protein diets, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aflatoxins↗
PubMed1987

Effect of dietary fat level on dose response relationships during aflatoxicosis in young chickens.

The effect of aflatoxin in poultry is greater on birds fed a low fat diet, but it is not known whether this effect is associated with a lower apparent minimum effective dose (MED), altered slope of the response curve, or both. Aflatoxin at 16 dosages ranging from 0 to 3.797 micrograms/g of feed was fed to six groups of 15 young chickens per treatment ingesting a 2 or 4% fat diet for 3 wk. The weights of the body, liver, bursa of Fabricius, and spleen and the total lipid content of the liver were measured. Mathematical models were fitted to the data and dose-response curves were predicted as continuous functions of aflatoxin concentration. Quadratic polynomials fit body weight and spleen weight whereas plateau-linear models fit liver weight and liver lipid content in both 2 and 4% fat diets. The weight of the bursa of Fabricius was fit equally well by quadratic and linear plateau models. Dietary fat had negligible effects on the apparent MED (micrograms of aflatoxin per gram of feed) for body, liver and spleen weights, which were calculated from the modeling approach to be 1.37 and 1.41, 1.68 and 1.69, and 1.49 and 1.46 on 2 and 4% fat diets, respectively. The apparent MED for liver lipid content was appreciably lower for birds fed the 2% fat diet than those fed the 4% fat diet (.88 and 1.62, respectively). Similarly, the apparent MED for the bursa was 1.48 and 1.74 for birds fed the 2 and 4% fat diets, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aflatoxins↗
PubMed1984

Lifetime productivity of purebred and crossbred cows of Angus and milking shorthorn parentage: weights and scores.

Lifetime productivity of 242 purebred and reciprocal crossbred Angus (A) and Milking Shorthorn (M) cows was studied. Cows were born in the fall during the 5-yr period from 1966 through 1970. Data from each parity, one through six, were analyzed separately by the method of least-squares. The basic statistical model included effects of breed of cow and year of cow birth plus the first-order interaction. Calf weight data were adjusted for effects of sex and calf age. Production stage was included for analyses of cow weights and condition scores. Data from parities seven through 13 were combined in one analysis with the effect of parity added to the model. Appropriate contrasts of estimates of breed means provided estimates of additive, heterotic, maternal and grandmaternal effects. Using pooled averages, crossbred cows were 22.5 kg (5.7%, P less than .01) heavier and .15 condition score units (5.3%, P less than .01) fatter than purebred cows. Condition scores of AM, MA and AA cows were higher (P less than .05) than those of MM cows. Calves from crossbred cows averaged 6.1 and 9.8 kg heavier (4.2 and 4.7%, P less than .01) at 120 and 210 d of age, respectively, than calves from purebred cows. Calves from AM, MA and MM dams were heavier (P less than .05) than those from AA dams. Calf weight at 210 d of age as a percentage of cow weight was used as a measure of efficiency of production. The heterosis contrast was 3.6% (P less than .01), which represented an 8.5% increase of the crossbreds relative to the mean of purebred cows (42.4%).

Animals↗
PubMed1982

Beef x beef and dairy x beef females mated to Angus and Charolais sires. I. Pregnancy rate, dystocia and birth weight.

Pregnancy rate of 310 females and birth weight, dystocia score and percentage of assisted births among 910 calves born from 1972 through 1977 were examined. Dams were 2 to 7 yr old and of Angus x Hereford (AH), Charolais x Hereford (CH), straightbred Hereford (HH) and Brown Swiss x Hereford (SH) breed types. Females were exposed to A and C bulls. Breed of dam affected (P less than .01) dystocia score (DS), percentage of assisted births and birth weight. When adjusted for birth weight of calf and dam's postcalving weight, CH and SH dams generally differed (P less than .01) from AH and HH dams in percentage of assisted births and DS. The AH and HH dams were not different (P greater than .01) in percentage of assisted births, DS or birth weight of calf. C-sired calves had higher birth weights (P less than .01) and their dams had higher DS (P less than .05). However, there was no difference between C- and A-sired calves in percentage of assisted births when data were adjusted for effects of birth weight of calf and weight of dam. Calf sex affected birth weight (P less than .01) but had little influence on DS or percentage of assisted births when birth weight was held constant. Male calves were 1.7 kg heavier at birth than females. Two-year-old dams had higher (P less than .01) DS and percentage of assisted births than did dams in all other age groups. Age of dam influenced birth weight (P less than .01), with paired comparisons of age classes showing differences between all age groups except 4- and greater than or equal to 5-yr-old cows. Year of birth was a source of variation (P less than .05) for all traits measured. In 1972, there was a higher mean DS and a higher percentage of assisted births (P less than .05) than in any other year. However, all calves born in 1972 were from 2-yr-old cows. Percentage difficulty and DS increased linearly (P less than .01) with birth weight. Each 1-kg increment in birth weight increased percentage difficulty by 2.6 percentage points and DS by .04 units. Dam's with heavier weights had calves that were heavier (P less than .01) at birth, but dystocia tended to decrease. Condition entering the breeding pasture influenced (P less than .05) pregnancy rate among 2- to 7-yr-old cows. Thin (score w) cows had a lower conception rate than average flesh (score 3) or fat (score 4) cows. Date of calving prior to the breeding season also affected (P less than .05) pregnancy rate. Each 10 d later calving resulted in a 1.2% reduction in conception rate. No significant sources of variation were observed for pregnancy rate among yearling heifers. Pregnancy rates ranged from 97.1% for CH and SH heifers to 86.9% for HH females. Yearling AH females were intermediate at 93.5%.

Animals↗
PubMed1982

Beef X beef and dairy X beef females mated to Angus and Charolais sires II. Calf growth, weaning rate and cow productivity.

Preweaning growth of 814 progeny was studied, and weaning rate and kilograms of calf weaned/cow exposed were determined for 310, 2- to 7-yr-old angus x Hereford (AH), Charolais X Hereford (CH), straight bred Hereford (HH) and Brown Swiss X Hereford (SH) cows mated to Angus and Charolais bulls. Charolais-sired calves grew more rapidly (P less than .01) then Angussired calves were heavier (P less than .01) at 130 and 210 d of age. Progeny of SH females grew faster (P less than .05) and were the heaviest at 130 (164 kg) and 210 (231 kg) d, whereas calves from HH dams grew the slowest and weighed the least (P less than 0.5) at 130 (125 kg) and 210 (180 kg) d of age. Progeny from AH and CH dams had similar 130-d weights (CW130) and made similar daily gains from birth to 130 of age (ADGI). Calves from CH females gained faster (P less than .05) from 130 to 210 d (ADG2) and had higher (P less than .05) 210-d weights (CW210) than did calves from AH dams. ADG1 and ADG2 of male calves were .043 and .072 kg/d greater, respectively (P less than .01) than those of heifer calves. Age of dam influenced (P less than .01) calf preweaning gains and weights. Calves from 4- to 7-yr old cows had greater (P less than .05) ADG1 and ADG2 and higher (P less than .05) CW130 and CW210 than progeny of younger dams. Progeny of 2-yr-old cows grew more slowly (P less than .05), and were last (P less than .05) in all traits (ADG1, ADG2, CW130 and CW210), whereas progeny of 3-yr-old cows were intermediate to those of 2 and 4- to 7-yr-old females. Cow breed type influenced (P less than .01) weaning rate (WR) and kilograms of calf weaned/cow exposed. SH females has the highest WR (83.4%), AH and CH were intermediate at 76 .8 and 77.7%, respectively, and HH dams had the lowest (P less than .05) WR, 66.4 calves/100 cows exposed. SH cows weaned 34.6 kg more (P less than .05) calf/cow exposed than AH and CH dams. HH dams were least productive (P less than .05), weaning 122.3 kg calf/cow exposed. Dairy X beef dams (SH) weaned 47.6 kg more (P less than .01) calf/cow exposed than the average of beef X beef dams (AH, CH, HH). Dairy X beef females had the highest WR and weaned the heaviest calves.

Animals↗
PubMed1979

Aspergillosis and atopy in cystic fibrosis.

Forty-six patients with cystic fibrosis (CF) were studied for colonization and sensitization by Aspergillus organisms. The fungus was cultured from 21 of 37 (57%) patients who produced sputum. The non-CF sputum isolation rate was 6.5%. Sputum hyphae were seen in 95% of patients with positive cultures. Sputum eosinophilia accompanied colonization by Aspergillus. Aspergillus precipitins were found in 37% of CF patients; positive immediate skin tests were found in 39%. "Atopy" defined by skin test criteria was found in 46%. All of these findings were more common in patients with more severe disease (p less than 0.05). CF patients had predominant mold sensitivity in contrast to predominant pollen sensitivity in a control group of asthmatic subjects. Serum IgE concentrations were increased in 22% of CF patients. CF patients who had increased serum concentrations of IgE were more likely to have a family history of atopy. Wheezing was more common in those who were atopic, especially the group with predominant mold sensitivity who had more severe disease. Four patients fulfilled the diagnostic criteria for allergic bronchopulmonary aspergillosis (ABPA) during the time of study and follow-up. A fifth patient had ABPA diagnosed before the study. The incidence of ABPA during a 2-yr period in our CF population was 11%.

Adolescent↗
PubMed1971

Growth of Aspergillus repens in Flue-Cured Tobacco.

In laboratory tests, flue-cured tobacco inoculated with Aspergillus repens was stored at 75, 80, 85, 87, and 95% relative humidity at 20 and 30 C. Samples were taken weekly for 4 weeks and evaluated for mold growth (colony count) and moisture content (MC). The weekly rate of fungus increase was slower at 20 C than at 30 C. Tobacco at 20 C with MC between 25 to 30% supported a slight to moderate increase in A. repens after 3 weeks of storage. However, tobacco at the same MC stored at 30 C was subject to rapid invasion by the fungus in as few as 1 to 2 weeks. Tobacco with MC above 30% stored at either 20 or 30 C became moldy in about 1 week. A mold index is proposed for evaluating populations of A. repens in tobacco.

Journal Article↗