Hormonal profiles of callipyge and normal sheep.

Five sheep expressing the callipyge gene, which causes muscle hypertrophy, were compared with five normal sheep to determine whether endocrine differences existed between genotypes. Blood samples were taken at 15-min intervals for 6 h to measure serum concentrations of growth hormone and insulin. Thyroxine and IGF-I levels were determined in single samples. No differences were found in mean serum growth hormone concentrations, growth hormone pulse amplitude, or pulse frequency (P > .3). Insulin concentrations were not different between genotypes before or after feeding (4.5 +/- 1.3 ng/mL callipyge vs 4.9 +/- 1.7 ng/mL normal, P > .4). The IGF-I concentrations did not differ (273.8 +/- 17.6 ng/mL callipyge vs 261.4 +/- 12.3 ng/mL normal). Serum thyroxine concentrations also were not different (5.9 +/- 2.3 microg/mL for callipyge vs 5.1 +/- 2.1 microg/mL normal, P > .3). In a separate experiment, five ewe lambs with and five without the callipyge gene were stressed to determine whether the adrenocortical response to stress differed between genotypes. Blood samples were taken at 15-min intervals for 2 h before, during, and after restraint stress. Restraint increased serum cortisol concentrations in both groups (P < .001), but genotypes did not differ at any time (P > .3). These results suggest that differences in muscling are not due to differences in systemic hormone secretion. The results of the second experiment indicate that callipyge and normal sheep have similar adrenocortical responses to stress.

The effects of neurotransmitter antagonists and glucose on luteinizing hormone secretion in growth-restricted wethers.

Chronic undernutrition results in reduced secretion of luteinizing hormone (LH). Two experiments were conducted in wethers whose LH secretion was suppressed by growth restriction caused by feeding a maintenance ration. The first study examined neurotransmitters that may be actively inhibiting LH secretion during growth restriction. The effects of various neurotransmitter antagonists were investigated: pimozide (PIM, dopamine), cyproheptadine (CYP, serotonin), pyrilamine (PYR, H1), cimetidine (CMT, H2) and propranolol (PRO, beta-adrenergic) in wethers specifically fed to maintain a body weight of 28 kg (GR, n = 7) and in full fed control wethers (n = 5). Blood samples were taken at 15 min intervals for 4 h before and after drug administration. Serum LH concentrations were determined by radioimmunoassay (RIA). Only PIM increased (P < 0.01) serum LH pulse frequency in the GR wethers (pre 0.5 +/- 0.2 pulses per 4 h vs. post 2.6 +/- 0.9 pulses per 4 h). None of the drugs tested had an effect on the control wethers. Experiment 2 examined the effect of glucose administration (50, 100, or 150 mg i.v.) on LH secretion in GR wethers. Only the 150 mg dose significantly (P < 0.05) increased LH pulse frequency compared to the pre-injection period (1.1 +/- 0.3 vs. 2.0 +/- 0.4 pulses per 4 h). After refeeding, LH pulse frequency and serum glucose concentrations increased. Proglumide, a cholecystokinin (CCK) antagonist, did not block this increase (2.1 +/- 0.4 vs. 2.2 +/- 0.3 pulses per 4 h). These data suggest that dopamine inhibits LH secretion in GR wethers and that increasing serum glucose concentrations increased LH secretion.

Detection of alpha 1-antitrypsin Z and S mutations by polymerase chain reaction-mediated site-directed mutagenesis.

alpha 1-Antitrypsin (A1AT) deficiency is a relatively common autosomal recessive disease, resulting most often from a single base pair (1 bp) substitution called the Z mutation. Previous genetic tests for carriers and affected patients have relied on quantitative binding of radioactive probes to an amplified gene product, because the mutation does not occur within a restriction enzyme site. Using polymerase chain reaction (PCR)-mediated site-directed mutagenesis, one can introduce a base substitution near the mutation site, such that an inexpensive restriction enzyme (Taq I) can be used to differentiate normal subjects, carriers, and affected patients. We have applied this method to the detection of the Z mutation and the S mutation, which in heterozygotes with a Z allele may lead to the development of symptoms similar to those in ZZ homozygous subjects.

Chronic bilateral bundle-branch block. Long-term observations in ambulatory patients.

During a period of 28 months, all patients (79) who presented with bilateral bundle-branch block were selected for study from a private practice outpatient population. They were followed prospectively from the date of entry into the study and their charts were reviewed retrospectively. The average age of the participants was 73-3 years and they were observed clinically for a cumulative period of 4237 months (353-08 years). A high incidence of severe heart disease and death was noted among the study group. Twenty-four (30-3%) had a New York Heart Association functional classification of 3 or 4. Eight (10-1%) died. Only one patient died suddenly and he had had a stable electrocardiographic pattern of bilateral bundle-branch block for a period of 118 months (9 years 10 months). Seven patients required permanent pacemakers. In 6 instances death resulted from pump failure; in one it was the result of lung cancer. In none of these 7 individuals did rhythm disturbances contribute to death. In most cases vertigo was not of cardiac origin (88-2%). Eight patients had 11 major surgical procedures with no significant cardiac sequelae. Our observations suggest that elderly patients with chronic bilateral bundle-branch block should be managed conservatively. The prognosis in these patients appears primarily to be related to the degree of myocardial disease rather than to the conduction disorder.