Relationships of serum insulin-like growth factor I concentrations to growth, composition, and reproductive traits of swine

Insulin-like growth factor I (IGF-I) is a peptide hormone that has been shown to be involved in metabolic regulation of growth and reproduction in livestock species. The objectives of this study were to quantify concentrations of IGF-I in growing pigs and determine whether IGF-I concentration can be used as a predictor of growth, composition, and reproductive traits. Forty male and 60 female pigs, divided equally between two locations, were weighed and bled at 3-wk intervals from 6 to 21 wk of age. At each sampling, two blood samples were collected via jugular venipuncture at an interval of at least 1 h. Serum was separated and IGF-I concentration determined via RIA. Pigs were weighed at each sampling date. Backfat and longissimus muscle area were measured with the use of B-mode ultrasound and adjusted to 100 kg. Age at puberty and first-parity litter size were measured on gilts. Effects of age, sex, location, and pig within sex x location on log-transformed IGF-I concentrations were determined by analyzing data as a split-plot. Performance traits were fitted to a model including the effects of IGF-I concentration, sex, location, and interactions. The IGF-I concentrations increased (P < .05) from 3 to 18 wk of age before dropping at 21 wk of age. Concentrations increased more rapidly in males than in females and differed significantly between sexes from 12 to 21 wk of age. Repeatability of IGF-I concentration was .29 +/- .02; IGF-I concentrations of samples collected at 6 wk were not correlated with those at later ages. Correlations between IGF-I concentrations of samples at later ages ranged from .27 to .51. Heritability of IGF-I concentration was .27 +/- .07. There was a tendency for weight to be affected by a sex x age interaction (P = .09). Weight of boars exceeded weight of gilts only at 21 wk (111.4 +/- 1.1 vs 107.1 +/- .8 kg). Regressions of weight on IGF-I concentrations were positive at all ages but greatest at 6 wk. The IGF-I concentration did not affect backfat thickness, longissimus area, percentage of lean, age at puberty, or litter size.     

Clinical factors useful in predicting aortic valve structure in patients > 40 years of age with isolated valvular aortic stenosis

A number of reports have described the frequency of coronary arterial narrowing in patients with valvular aortic stenosis. No published reports have examined the structure of the stenotic aortic valve in adults and related the valve structure to variables, including coronary arterial narrowing, useful in predicting that structure. One hundred eighty-eight patients having aortic valve replacement for isolated valvular aortic stenosis were studied. All patients were > 40 years of age at the time of aortic valve replacement, all had coronary angiograms preoperatively, and of 182 patients (97%) measurements of serum total cholesterol had been obtained and 184 (98%) had body mass index calculated. The structure of the operatively excised valve was classified as unicuspid or bicuspid (congenitally malformed), or tricuspid aortic valve. A logistic regression model was developed that found 4 factors (age, serum total cholesterol, angiographic coronary artery disease and body mass index) to be predictive of aortic valve structure: (1) Patients with at least 3 or all 4 factors high or present (i.e., age > 65 years, serum total cholesterol > 200 mg/dl, body mass index > 29 kg/m2 and coronary artery disease) had a low probability (10 to 29%) of having a congenitally malformed valve; (2) patients with at least 3 or all 4 factors low or absent (i.e., age < or = 65 years, serum total cholesterol < or = 200 mg/dl, body mass index < or = 29 kg/m2, and no coronary artery disease) had a high probability (72 to 90%) of having a congenitally malformed valve.(ABSTRACT TRUNCATED AT 250 WORDS)     

Native-like structure of a protein-folding intermediate bound to the chaperonin GroEL

The chaperonin GroEL binds nonnative proteins in its central channel through hydrophobic interactions and initiates productive folding in this space underneath bound co-chaperone, GroES, in the presence of ATP. The questions of where along the folding pathway a protein is recognized by GroEL, and how much structure is present in a bound substrate have remained subjects of discussion, with some experiments suggesting that bound forms are fully unfolded and others suggesting that bound species are partially structured. Here we have studied a substrate protein, human dihydrofolate reductase (DHFR), observing in stopped-flow fluorescence experiments that it can rapidly bind to GroEL at various stages of folding. We have also analyzed the structure of the GroEL-bound protein using hydrogen-deuterium exchange and NMR spectroscopy. The pattern and magnitude of amide proton protection indicate that the central parallel beta-sheet found in native DHFR is present in a moderately stable state in GroEL-bound DHFR. Considering that the strands are derived from distant parts of the primary structure, this suggests that a native-like global topology is also present. We conclude that significant native-like structure is present in protein-folding intermediates bound to GroEL.     

The discrimination of marijuana intoxication

Forty Ss, 20 males and 20 females, observed a videotape that showed four males interacting in a social setting under four different drug conditions; coltsfoot, placebo, marijuana low dose, and marijuana high dose. The observers attempted to discriminate the level of intoxication of the four males in each condition. The observers accurately detected the level of intoxication in the high dose condition. While marijuana experienced users were more successful in detecting levels of intoxication, the sex of the observer was not significant. Behaviors used to discriminate intoxication and the implications of these results to defining intoxication are discussed.     

Margatoxin increases dopamine release in rat striatum via voltage-gated K+ channels

The distribution of iodinated margatoxin ([125I]margatoxin) binding sites in rat was investigated by autoradiography. Rat striatum expresses a high density of margatoxin binding sites and, therefore, the effects of margatoxin, charybdotoxin and iberiotoxin have been studied on [3H]dopamine release from rat striatal slices in vitro. Margatoxin (0.1-100 nM) and charybdotoxin (10-1000 nM), but not iberiotoxin increased the spontaneous and the electrically evoked [3H]dopamine release. [3H]dopamine release by margatoxin was inhibited by tetrodotoxin and omega-conotoxin GVIA, but not by atropine, naloxone, N(omega)-nitro-L-arginine and neurokinin or neurotensin receptor antagonists. In the buffer solution used for release experiments, [125I]margatoxin labels a maximum of 0.12 pmol of sites/mg protein in rat striatal membranes with a Kd of 5 pM. [125I]margatoxin binding was inhibited by margatoxin (Ki of 4 pM), charybdotoxin (Ki of 162 pM) but not by iberiotoxin. We conclude that inhibition of margatoxin-sensitive voltage-gated K+ channels increases [3H]dopamine release demonstrating their role in repolarization of nigrostriatal projections. In contrast, iberiotoxin-sensitive, high-conductance Ca2+-activated K+ channels are not involved in release of [3H]dopamine.