Hidden process models for animal population dynamics.

Hidden process models are a conceptually useful and practical way to simultaneously account for process variation in animal population dynamics and measurement errors in observations and estimates made on the population. Process variation, which can be both demographic and environmental, is modeled by linking a series of stochastic and deterministic subprocesses that characterize processes such as birth, survival, maturation, and movement. Observations of the population can be modeled as functions of true abundance with realistic probability distributions to describe observation or estimation error. Computer-intensive procedures, such as sequential Monte Carlo methods or Markov chain Monte Carlo, condition on the observed data to yield estimates of both the underlying true population abundances and the unknown population dynamics parameters. Formulation and fitting of a hidden process model are demonstrated for Sacramento River winter-run chinook salmon (Oncorhynchus tshawytsha).

Suppression of hypothalamic-pituitary-adrenal axis activity with inhaled flunisolide and fluticasone propionate in adult asthma patients.

BACKGROUND: Suppression of the hypothalamic-pituitary-adrenal (HPA) axis, a potential systemic effect of inhaled corticosteroid therapy, can be quantified by monitoring serum, urinary, and salivary cortisol levels. OBJECTIVES: 1) Compare the effects on HPA axis of the inhaled corticosteroids flunisolide and fluticasone propionate versus placebo and oral prednisone. 2) Estimate dose-potency ratio for HPA-axis suppression. METHODS: Multicenter, randomized, placebo-controlled, open-label, 21-day trial. Active regimens were flunisolide 500 and 1,000 microg, twice daily; fluticasone propionate 110, 220, 330, and 440 microg, twice daily; and prednisone, 7.5 mg daily. Enrolled patients were nonsmokers, 18 to 50 years of age, with persistent mild-to-moderate asthma and had not used oral, nasal, or inhaled corticosteroids for 6 months before study. Main outcome measures were area under serum cortisol concentration curve for 22 hours (AUC(0-22h)); 24-hour urinary cortisol level; and 8 AM salivary cortisol level. RESULTS: One hundred fifty-three patients were randomly assigned to active treatment or placebo; 125 patients completed the study and were at least 80% compliant with their regimens. Both fluticasone propionate and flunisolide caused dose-dependent suppression of HPA axis, which was statistically greater for fluticasone propionate (P = 0.0003). Dose-potency ratio showed 4.4 times more serum-cortisol suppression/microgram increase in dose with fluticasone propionate than with flunisolide. Diurnal pattern of serum cortisol suppression was persistent with fluticasone propionate and "remitting" with flunisolide. Salivary and urinary cortisol data were qualitatively similar to serum cortisol results. CONCLUSIONS: Fluticasone caused significantly more suppression of HPA axis than flunisolide. Flunisolide may provide a safe option for patients with asthma requiring long-term inhaled corticosteroid therapy.

Interaction of asthmatics and their spouses: A preliminary study of individual differences.

Some asthmatics show evidence of airways reactivity triggered by strong emotions. Six case studies of married patients with severe asthma are reported. The videotaped interactions of the asthmatic and his/her spouse were coded for affect and behavior. Repeated measures of pulmonary function and affective state were recorded before and after two interaction tasks. Over the course of the experimental period, two patients' pulmonary function improved and four patients' deteriorated. In general, decreased pulmonary function was associated with more self-rated hostility and depression. The results are discussed in terms of their implications for the intra- and interpersonal factors that are important in asthma management.

Human lung cell beta 2-adrenergic receptors desensitize in response to in vivo administered beta-agonist.

Few studies have addressed whether target tissue adrenergic receptors in humans undergo desensitization in response to agonist administration. To determine whether lung cell beta 2-adrenergic receptors (beta 2-AR) undergo such desensitization, we harvested bronchial epithelial cells and alveolar macrophages via bronchoscopy from eight normal subjects before and after inhalation of six doses of the beta-agonist metaproterenol given over 24 h. After metaproterenol inhalation, beta 2-AR expression as determined by 125I-labeled cyanopindolol binding decreased approximately 70% on bronchial epithelial cells, from 6.3 +/- 0.7 to 2.0 +/- 0.2 fmol/mg (P < 0.001) and to a similar extent on macrophages from 13.3 +/- 0.4 to 3.9 +/- 0.6 fmol/mg (P < 0.001). Agonist inhalation also resulted in impairment of beta 2-AR function in both cell types. With bronchial epithelial cells, maximal isoproterenol-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) accumulation decreased from 9.5 +/- 1.8 to 4.9 +/- 1.2 pmol/10(6) cells (P = 0.003), which amounts to a 48 +/- 6% desensitization. Isoproterenol-stimulated cAMP accumulation in alveolar macrophages decreased from 39.5 +/- 9.0 to 2.9 +/- 0.3 pmol/10(6) cells (P = 0.007), equivalent to 86 +/- 5% desensitization. The cAMP response to forskolin in both cell types was unaffected by metaproterenol inhalation. Thus administration of inhaled beta-agonists results in substantial downregulation and functional desensitization of lung cell beta 2-AR. This supports the concept of a dynamically regulated beta 2-AR in humans, the function of which can be attenuated in relevant target tissues by administration of standard doses of beta-agonist.

Clinical features of vocal cord dysfunction.

Vocal cord dysfunction (VCD) is a respiratory condition characterized by adduction of the vocal cords with resultant airflow limitation at the level of the larynx. Previously, this condition was described in case reports and in small series. This study reviews all patients hospitalized from 1984 through 1991 in whom VCD was diagnosed. Demographic, historical, physiologic, laboratory, and psychiatric factors were statistically analyzed. Ninety-five patients met the criteria for proved VCD; of these, 53 also had asthma. All patients had laryngoscopic evidence of paradoxical vocal cord motion, with inspiratory and/or early expiratory vocal cord adduction. The patients with VCD without asthma were predominantly young women. In these patients, asthma had been misdiagnosed for an average of 4.8 years. Their medications were identical to those of a control group of patients with severe asthma. Thirty-four of the 42 patients with VCD without asthma were receiving prednisone regularly at an average daily dose of 29.2 mg. Medical utilization was enormous with the VCD group, averaging 9.7 emergency room visits and 5.9 admissions in the year prior to presentation. Also, 28% of the patients with VCD had been intubated. We conclude that VCD can masquerade as asthma and that it often coexists with asthma. This study helps to define the historical and clinical features of VCD.

Quantitative computed tomography detects air trapping due to asthma.

OBJECTIVE: The purpose of this study was to prospectively see if quantitative computed tomography (QCT) could separate asthmatic patients from normal control subjects. The QCT results were also correlated with the pulmonary function tests (PFT) that were done on both the asthmatic patients and control subjects. SUBJECTS AND METHODS: Eighteen adult nonsmoking asthmatics and 22 adult control subjects were entered into the study. Quantitative CT was performed at the level of the transverse aorta and just above the diaphragm at both end inspiration and end expiration in all patients and control subjects: 10-mm and 1.5-mm collimation using a high spatial frequency algorithm was used to obtain the QCT examinations. The percent of pixels below -900 Hounsfeld units, pixel index, in each of the QCT axial images of the lungs was calculated for each asthmatic and control subject in the study. Pulmonary function testing was performed on both the asthmatics and control subjects and included determination of FEV1, FVC, FRC, RV, and TLC. Unpaired Student's t test analysis of the QCT data was done to statistically compare the asthmatics with the control subjects. Linear regression analysis was done to compare the QCT results with PFT data on the asthmatics and control subjects. RESULTS: When scans were performed at end expiration, at a level immediately superior to the diaphragm, the mean pixel index was significantly higher in asthmatic subjects compared with normal individuals on both CT (mean for normal subjects 0.16 vs 4.45 for asthmatics, p < 0.004) and high-resolution CT (HRCT) images (mean for normal subjects 1.04 vs 10.03 in asthmatics, p < 0.0001) indicating more areas of low attenuation in asthmatics. The CT and HRCT images from the lower lung zones that were performed at end expiration provided the best separation between the groups. The pixel index on expiration correlated with the degree of air trapping and airflow limitation in the asthmatic group based on FEV1, FRC, RV, and to a lesser extent, FVC. CONCLUSION: Expiratory QCT is a useful method to assess air trapping in asthmatic patients. The percent of abnormal lung in asthmatics as determined by QCT has a significant correlation with the PFTs that reflect air trapping in asthmatic patients. Quantitative CT may be helpful in assessing degrees of air trapping present in other diseases affecting the airways.

Vocal cord dysfunction mimicking bronchial asthma.

Vocal cord dysfunction is a possible cause of wheezing and dyspnea in patients who do not respond to conventional asthma therapy. A carefully taken history, pulmonary function testing, and, most important, direct visualization with a flexible laryngoscope during an acute attack allow physicians to differentiate vocal cord dysfunction from asthma. Speech therapy, inhalation of helium and oxygen, and psychiatric counseling play a role in management.

Selective amplification of an mRNA and related pseudogene for a human ADP-ribosylation factor, a guanine nucleotide-dependent protein activator of cholera toxin.

ADP-ribosylation factors (ARFs) are approximately 20-kDa proteins that act as GTP-dependent allosteric activators of cholera toxin. With deoxyinosine-containing degenerate oligonucleotide primers corresponding to conserved GTP-binding domains in ARFs, the polymerase chain reaction (PCR) was used to amplify simultaneously from human DNA portions of three ARF genes that include codons for 102 amino acids, with intervening sequences. Amplification products that differed in size because of differences in intron sizes were separated by agarose gel electrophoresis. One amplified DNA contained no introns and had a sequence different from those of known ARFs. Based on this sequence, selective oligonucleotide probes were prepared and used to isolate clone psi ARF 4, a putative ARF pseudogene, from a human genomic library in lambda phage EMBL3. Reverse transcription-PCR was then used to clone from human poly(A)+ RNA the cDNA corresponding to the expressed homolog of psi ARF 4, referred to as human ARF 4. It appears that psi ARF 4 arose during human evolution by integration of processed ARF 4 mRNA into the genome. Human ARF 4 differs from previously identified mammalian ARFs 1, 2, and 3. Hybridization of ARF 4-specific oligonucleotide probes with human, bovine, and rat RNA revealed a single 1.8-kilobase mRNA, which was clearly distinguished from the 1.9-kilobase mRNA for ARF 1 in these tissues. The PCR provides a powerful tool for investigating diversity in this and other multigene families, especially with primers targeted at domains believed to have functional significance.

Phorbol ester-induced inhibition of the beta-adrenergic system in pulmonary endothelium: role of a pertussis toxin-sensitive protein.

To investigate possible cellular mechanisms for how activation of protein kinase C inhibits the relaxation caused by isoproterenol, we studied the effect of the protein kinase C activator 4 beta-phorbol-12 beta-myristate-13 alpha-acetate (PMA) on the increase in cyclic AMP (cAMP) production and adenylate cyclase activity caused by isoproterenol in bovine pulmonary artery endothelial cells. Treatment of intact cells with PMA prevented in a time- and dose-dependent manner the increase in cAMP production caused by isoproterenol, whereas 4 alpha-phorbol-12 beta-myristate-13 alpha-acetate (4 alpha-PMA), which does not activate protein kinase C, did not affect isoproterenol-induced cAMP production. PMA also reduced the increase in adenylate cyclase activity caused by isoproterenol, forskolin, and Gpp(NH)p. To test the hypothesis that the inhibitory effect of PMA is mediated via a pertussis toxin-sensitive G protein, we determined whether pretreatment of the cells with pertussis toxin would prevent the inhibitory effects of PMA. In pulmonary endothelial cells, pertussis toxin ADP-ribosylated an Mr 40,000 peptide that comigrated with the pertussis toxin substrate of human erythrocytes. Pertussis toxin treatment eliminated the inhibitory effect of PMA on isoproterenol-stimulated cAMP production and adenylate cyclase activity. Thus, the protein kinase C activator PMA inhibits the increase in cAMP production and adenylate cyclase caused by isoproterenol. This inhibitory effect in endothelial cells appears to be mediated via a pertussis toxin-sensitive protein.