Reduced cell proliferation in fetal lung after maternal administration of pilocarpine. A scintillation autoradiographic study

Fetuses were obtained on the 28th gestational day from pregnant New Zealand white rabbits treated daily, on the 24th through the 27th gestational day, with pilocarpine HCl, 5 mg/kg in saline, or saline alone. Lung fragments from these fetuses were incubated for two hours in medium containing ³H-thymidine. Scintillation autoradiography of 1-μm-thick sections of these fetal lungs revealed that the lung tissue from pilocarpine-treated fetuses had significantly lower labelled cell indices for both alveolar epithelial cells and interstitial cells. These results indicate that pilocarpine treatment promotes differentiation of immature cells in the fetal lung at the expense of cell proliferation.     

Hypersensitivity to airborne spitting cobra snake venom.

BACKGROUND: Although the cytolytic, neurotoxic, and hemolytic actions of snake venoms are well known, the ability of airborne inhaled snake venom of the spitting cobra to induce asthma in snake handlers has not been reported. OBJECTIVE: To report the allergenicity of inhaled snake venom in a snake handler who developed increasing hypersensitivity to airborne venom, produced by spitting cobras during public demonstrations. METHODS: Serum samples were obtained from 2 handlers (our study patient and another snake handler who reported developing wheezing when handling spitting cobras), and desiccated venom was obtained from 9 species to which the handlers were exposed. Serum from an asymptomatic and nonatopic snake handler exposed to the same snake species was used as a control. Phosphate-buffered saline extracts were prepared from the desiccated venom, proteins in the venom extracts were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and immunoblotting was performed. Inhibition enzyme-linked immunosorbent assays (ELISAs) were performed to demonstrate cross-reactivity. RESULTS: The study patient had never been previously bitten by a cobra. Wheezing occurred rapidly on inhalational exposure and was reversed by inhalation of salbutamol. The patient had developed IgE antibodies to 9 different snake venoms on Western immunoblots, with major IgE binding proteins of 59 to 63 kDa and 8 to 15 kDa. The cross-reactive nature of the IgE epitopes in the venoms in the different species was also confirmed by 50% inhibition of IgE binding in an ELISA by preincubation with unrelated species. Life-threatening sensitivity of the patient was sustained after a long period of avoidance. CONCLUSIONS: We propose that aerosolized snake venom be considered a new potential source of allergens that may result in anaphylaxis on subsequent exposure. Further studies of the development of specific IgE sensitization following snakebites and the risks of such sensitization should be conducted on snake handlers, particularly those who demonstrate the spitting species.     

Immunity to Influenza in Ferrets X. Intranasal Immunization of Ferrets with Inactivated Influenza A Virus Vaccines

The response of ferrets after intranasal inoculation of inactivated A/Hong Kong/68 (H3N2) influenza virus vaccines is reported. Normal ferrets given either saline vaccine in drops or freeze-dried vaccine in an aerosol intranasally did not produce detectable serum or nasal hemagglutination inhibiting antibody and were found to be completely susceptible to challenge infection with A/Hong Kong/68 virus. Intranasal saline vaccine did not produce an additive effect on the response of ferrets simultaneously given the same vaccine intramuscularly with adjuvant. Ferrets primed by previous infection with A/PR/8/34 (H0N1) influenza virus, however, responded to intranasal immunization with saline A/Hong Kong/68 virus vaccine and produced serum and nasal antibody. These animals were found to be partially resistant to challenge infection, in contrast to similar animals given saline vaccine intramuscularly which were completely resistant to challenge infection. Primed ferrets did not respond after immunization with the freeze-dried aerosol vaccine, but this may have been due to a failure of the aerosol to be inhaled satisfactorily.     

Effects of a yearlong moderate-intensity exercise and a stretching intervention on sleep quality in postmenopausal women

STUDY OBJECTIVES: To examine the effects of a moderate-intensity exercise or stretching intervention and changes in fitness, body mass index, or time spent outdoors on self-reported sleep quality and to examine the relationship between the amount and timing of exercise and sleep quality. DESIGN: A randomized intervention trial. SETTING: A cancer research center in Seattle, Washington. PARTICIPANTS: Postmenopausal, overweight or obese, sedentary women not taking hormone replacement therapy, aged 50 to 75 years, and recruited from the Seattle metropolitan area. INTERVENTIONS: A yearlong moderate-intensity exercise (n=87) and a low-intensity stretching (n=86) program. MEASUREMENTS AND RESULTS: Among morning exercisers, those who exercised at least 225 minutes per week had less trouble falling asleep (odds ratio [OR]: 0.3, P < or = .05) compared with those who exercised less than 180 minutes per week. However, among evening exercisers, those who exercised at least 225 minutes per week had more trouble falling asleep (OR: 3.3, P < or = .05) compared to those who exercised less than 180 minutes per week. Stretchers were less likely to use sleep medication (OR = 0.4, P < or = .05) and have trouble falling asleep (OR: 0.7, P < or = .10) during the intervention period compared with baseline. A greater than 10% versus a 1% or less increase in maximum O2 consumption over the year was associated with longer sleep duration (P < or = .05), less frequently falling asleep during quiet activities (P < or = .05), and less use of sleep medication (P < or = .05). Reductions in body mass index and increases in time spent outdoors had inconsistent effects on sleep quality. CONCLUSIONS: Both stretching and exercise interventions may improve sleep quality in sedentary, overweight, postmenopausal women. Increased fitness was associated with improvements in sleep. However, the effect of moderate-intensity exercise may depend on the amount of exercise and time of day it is performed.     

Synthesis,storage and release of [14C]acetylcholine in isolated rat diaphragm muscles

1. Segments of rat diaphragms were kept in choline-free media for 4 hr and were then exposed to a physiological concentration of [¹⁴C]-choline (30 μM) at 37° C. The synthesis, storage and subsequent release of [¹⁴C]acetylcholine by the muscles was assessed by isotopic- and bio-assays after isolation of the transmitter by paper electrophoresis.2. Replacement of endogenous acetylcholine (0·92 μ-mole/kg) with labelled acetylcholine proceeded slowly at rest, but rapidly during nerve stimulation. [¹⁴C]Acetylcholine accumulated most rapidly when hydrolysis of the released transmitter, and thus the re-use of endogenous choline, was prevented by an esterase inhibitor. Fully replaced stores were maintained during nerve stimulation by synthesis rates sufficient to replenish at least 35% of the store size in 5 min.3 In the presence of hemicholinium-3, which inhibits choline uptake, acetylcholine stores declined rapidly during stimulation, and residual synthesis was slight, indicating little intraneural choline. Net choline uptake into nerve terminals was estimated from the highest observed synthesis rate and from previous measurements of the number and size of terminals, as 3-6 p-mole/cm² sec.4. Transmitter synthesis was localized in the region of end-plates, and was reduced to a few per cent of normal 6 weeks after phrenic nerve section. Release experiments suggested that at least half of the acetylcholine in phrenic nerves is in their terminals; from this content and the morphology of the terminals, the average concentration of transmitter in the whole endings would appear to be about 50 m-mole/l. Homogenization of the muscles freed choline acetyltransferase into solution, but left some [¹⁴C]acetylcholine associated with small particles, presumably synaptic vesicles.5. Resting transmitter release was about 0·013% of stores/sec. With 360 nerve impulses at 1-20/sec, release increased up to 0·43% of stores/sec, and amounted to 3·5-7 × 10^-18 moles per end-plate per impulse. The release rate was unaffected by the doubling of store size which occurred with eserine, but the extra transmitter did help to maintain releasable stores during prolonged stimulation. Experiments with fractional store labelling indicated that newly synthesized acetylcholine was preferentially released.6. Preformed [³H]acetylcholine was not taken up and retained by muscle or nerve cells in the absence of an esterase inhibitor. With eserine present, labelled acetylcholine was taken up uniformly by muscle segments; when eserine was then removed, radioactive acetylcholine remained only near neuromuscular junctions.     

Cloning and characterization of a protective outer membrane lipoprotein of Actinobacillus pleuropneumoniae serotype 5.

The gene encoding an outer membrane lipoprotein (omlA) of Actinobacillus pleuropneumoniae serotype 5 was cloned, and the protein was expressed in Escherichia coli. One open reading frame of 1,104 bp was detected that encoded a protein (OmlA) with a predicted molecular mass of 40 kDa. A comparison with the omlA gene and the corresponding protein of A. pleuropneumoniae serotype 1 (G.-F. Gerlach, C. Anderson, S. Klashinsky, A. Rossi-Kampos, A.A. Potter, and P.J. Wilson, Infect. Immun. 61:565-572, 1993) revealed that the nucleic acid sequences had an overall sequence identity of 62.9% and the deduced amino acid sequences showed a sequence agreement of 57.3%. Both proteins were antigenically distinct. In a Western blot (immunoblot) analysis using a specific antiserum against A. pleuropneumoniae serotype 5 OmlA, a homologous protein was detected in the reference strains of A. pleuropneumoniae serotypes 5A, 5B, and 10. Pigs immunized with this recombinant protein were protected from death in an aerosol challenge experiment with an A. pleuropneumoniae serotype 5 isolate.     

Monte Carlo calculation of the sensitivity of a commercial dose calibrator to gamma and beta radiation

The detection process used in a commercial dose calibrator was modeled using the GEANT 3 Monte Carlo code. Dose calibrator efficiency for gamma and beta emitters, and the response to monoenergetic photons and electrons was calculated. The model shows that beta emitters below 2.5 MeV deposit energy indirectly in the detector through bremsstrahlung produced in the chamber wall or in the source itself. Higher energy beta emitters (E > 2.5 MeV) deposit energy directly in the chamber sensitive volume, and dose calibrator sensitivity increases abruptly for these radionuclides. The Monte Carlo calculations were compared with gamma and beta emitter measurements. The calculations show that the variation in dose calibrator efficiency with measuring conditions (source volume, container diameter, container wall thickness and material, position of the source within the calibrator) is relatively small and can be considered insignificant for routine measurement applications. However, dose calibrator efficiency depends strongly on the inner-wall thickness of the detector.     

Immune complexes in ulcerative colitis and Crohn's disease.

Sera from 156 patients with ulcerative colitis and Crohn's disease were tested for the presence of immune complexes, by the detection of anti-complementary activity and 125I-labelled Clq precipitation. Using aggregated IgG, a comparison between the two tests indicated that the anti-complementary test was most sensitive to aggregates of 11S in size, while the 125I-labelled Clq test detected aggregates over 20S in size. Excess anti-complementary activity was common in patients with active bowel disease, and in those with extra-intestinal manifestations, particularly acute arthritis, ankylosing spondylitis and liver disease. Large complexes were only common in patients with liver disease. Immune complexes in the gut mucosa may play a role in the pathogenesis of these diseases, and the deposition of circulatory immune complexes may explain at least some of the extra-intestinal manifestations.