Measuring lung function in mice: the phenotyping uncertainty principle

2003 ◽  
Vol 94 (4) ◽  
pp. 1297-1306 ◽  
Author(s):  
Jason H. T. Bates ◽  
Charles G. Irvin
Keyword(s):  
Lung Function ◽  
Uncertainty Principle ◽  
Input Impedance ◽  
Respiratory Mechanics ◽  
Human Lung ◽  
Measurement Precision ◽  
The Other ◽  
Murine Models ◽  
Experimental Control ◽  
Lie Methods

Measuring lung function in mice is essential for establishing the relevance of murine models to human lung disease. However, making such measurements presents particular technical challenges due to the small size of the animal, particularly with regard to the measurement of respiratory flows. In this review, we examine the various methods currently available for assessment of lung function in mice and contrast them in terms of a concept we call the phenotyping uncertainty principle; each method can be considered to lie somewhere along a continuum on which noninvasiveness must be traded off against experimental control and measurement precision. Unrestrained plethysmography in conscious mice represents the extreme of noninvasiveness and is highly convenient but provides respiratory measures that are so tenuously linked to respiratory mechanics that they cannot be considered as meaningful indicators of lung function. At the other extreme, the measurement of input impedance in anesthetized, paralyzed, tracheostomized mice is precise and specific but requires that an animal be studied under conditions far from natural. In between these two extremes lie methods that sacrifice some precision for a reduction in the level of invasiveness, a promising example being the measurement of transfer impedance in conscious, restrained mice. No method is optimal in all regards; therefore, the appropriate technique to use depends on the application.

scholarly journals Assessment of Live Candidate Vaccines for Paratuberculosis in Animal Models and Macrophages

2009 ◽  
Vol 78 (3) ◽  
pp. 1383-1389 ◽  
Author(s):  
Gabriella M. Scandurra ◽  
Geoffrey W. de Lisle ◽  
Sonia M. Cavaignac ◽  
May Young ◽  
R. Pamela Kawakami ◽  
...  
Keyword(s):  
Side Effects ◽  
Bacterial Load ◽  
Economic Effect ◽  
Cost Effective ◽  
The Other ◽  
Murine Models ◽  
Initial Screening ◽  
Vaccine Candidates ◽  
Allelic Exchange ◽  
Potential Vaccine

ABSTRACT Mycobacterium avium subsp. paratuberculosis (basonym M. paratuberculosis) is the causative agent of paratuberculosis, a chronic enteritis of ruminants. To control the considerable economic effect that paratuberculosis has on the livestock industry, a vaccine that induces protection with minimal side effects is required. We employed transposon mutagenesis and allelic exchange to develop three potential vaccine candidates, which were then tested for virulence with macrophages, mice, and goats. All three models identified the WAg906 mutant as being the most attenuated, but some differences in the levels of attenuation were evident among the models when testing the other strains. In a preliminary mouse vaccine experiment, limited protection was induced by WAg915, as evidenced by a reduced bacterial load in spleens and livers 12 weeks following intraperitoneal challenge with M. paratuberculosis K10. While we found macrophages and murine models to be rapid and cost-effective alternatives for the initial screening of M. paratuberculosis mutants for attenuation, it appears necessary to do the definitive assessment of attenuation with a ruminant model.

Effect of aging alone on mechanical properties of the normal adult human lung

1977 ◽  
Vol 43 (6) ◽  
pp. 1054-1062 ◽  
Author(s):  
R. J. Knudson ◽  
D. F. Clark ◽  
T. C. Kennedy ◽  
D. E. Knudson
Keyword(s):  
Respiratory Mechanics ◽  
Human Lung ◽  
Age Groups ◽  
The Elderly ◽  
Elastic Recoil ◽  
Lung Volumes ◽  
Men And Women ◽  
Maximum Expiratory Flow ◽  
Alpha1 Antitrypsin ◽  
Adult Human Lung

For plethysmographic studies of respiratory mechanics, we selected, from a general population, 51 subjects, aged 25–75 yr, who had never smoked, had no present or past cardiorespiratory symptoms or disease, were alpha1-antitrypsin MM phenotypes, and were normal by physical examination, vectorcardiography, and chest roentgenography. Approximately equal numbers of men and women were represented in each of three age groups; 25–35, 36–64, and 65–75. Both sexes demonstrated loss of lung elastic recoil with age, most significant at high lung volumes, but the rate of loss was less than previously reported. Males had higher lung recoil than females of comparable age, but if lung size was taken into account, there were no sex differences in bulk elastic properties. Maximum expiratory flow diminished with age only at low volumes, suggesting that equal pressure points are more centrally located at low lung volumes in the elderly.

Measuring lung function in murine models of pulmonary disease

2004 ◽  
Vol 1 (3) ◽  
pp. 337-343 ◽  
Author(s):  
Peter D. Sly ◽  
Debra J. Turner ◽  
Zoltan Hantos
Keyword(s):  
Lung Function ◽  
Pulmonary Disease ◽  
Murine Models

scholarly journals Neutral glycosphingolipids and gangliosides of human lung and lung tumours

1979 ◽  
Vol 179 (1) ◽  
pp. 199-211 ◽  
Author(s):  
R Narasimhan ◽  
R K Murray
Keyword(s):  
Cancer Cells ◽  
Squamous Cell ◽  
Human Lung ◽  
Large Cell ◽  
The Other ◽  
Polymorphonuclear Leucocytes ◽  
Lung Tumours ◽  
Neutral Glycosphingolipids ◽  
Human Tumours

In order to help determine whether alterations of the profiles of glycosphingolipids occur consistently in human tumours, the neutral glycosphingolipids and gangliosides of nine lung tumours (one adenocarcinoma, four squamous cell, two mixed adeno-squamous cell, one large cell and one oat-cell carcinomata) were analysed. The control tissue consisted of adjacent lung; it contained neutral glycosphingolipids corresponding in properties to glucosyl-, lactosyl-, globotriaosyl- and globotetraosyl-ceramides. All of the tumours also contained these four neutral glycosphingolipids. However, in addition, five of the tumours (two of the squamous, the large cell and the two mixed adeno-squamous cell carcinomata) contained neutral glycosphingolipids corresponding in properties to lactotriaosyl- and neolactotetraosyl-ceramides; these same tumours also exhibited higher amounts of lactosylceramide than the other tumours analysed. Both of the two former neutral glycosphingolipids and very substantial amounts of the latter neutral glycosphingolipid were detected in pneumonic lung and in polymorphonuclear leucocytes; it thus appears possible that these particular compounds were derived from these latter cells rather than from the tumour cells. The ganglioside patterns of the tumours were almost equivalent in complexity to that exhibited by the control lung tissue. This study shows that the profiles of two major classes of glycosphingolipids (neutral glycosphingolipids and gangliosides) occurring in lung tumours are almost as complex as those of the parent tissue, a finding in contrast with the notably simplified patterns of these lipids found in many cancer cells grown in vitro. It also suggests that when lactotriaosyl- and neolactotetraosyl-ceramides and high amounts of lactosylceramide are detected in human tumours, the possibility must be considered that these compounds are derived from polymorphonuclear leucocytes.

scholarly journals Computed tomography patterns predict clinical course of idiopathic pulmonary fibrosis

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Byoung Soo Kwon ◽  
Jooae Choe ◽  
Kyung Hyun Do ◽  
Hee Sang Hwang ◽  
Eun Jin Chae ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Lung Function ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Exercise Capacity ◽  
Clinical Course ◽  
Usual Interstitial Pneumonia ◽  
The Other ◽  
Hrct Patterns

Abstract Background A new clinical guideline for idiopathic pulmonary fibrosis (IPF) uses high-resolution computed tomography (HRCT) patterns for diagnostic purposes. However, it is unknown how they relate to the IPF clinical course. We aimed to investigate whether HRCT patterns could be used to predict lung function changes and survival in patients with IPF. Methods Clinical data were retrospectively reviewed in 337 patients with IPF (all biopsy-proven cases). HRCT patterns were classified according to the 2018 IPF diagnostic criteria. Results The median follow-up was 46.9 months. The mean age was 62.5 years, and 74.2% were men. Among the HRCT patterns, usual interstitial pneumonia (UIP), probable UIP, indeterminate for UIP, and an alternative diagnosis were identified in 163 (48.4%), 110 (32.6%), 33 (9.8%), and 31 (9.2%) patients, respectively. The indeterminate for UIP group showed higher lung function and exercise capacity and better prognosis than the other groups. They also had a lesser decline in lung function than the other groups during follow-up. In the multivariate Cox analysis, which was adjusted by age, smoking status, lung function, exercise capacity, and use of antifibrotic agents, indeterminate for UIP pattern was found to be an independent prognostic factor (hazard ratio 0.559, 95% confidence interval 0.335–0.933, P = 0.026). However, the probable UIP group had similar lung function changes and prognosis when compared the UIP group. Conclusions Our results suggest that indeterminate for UIP pattern on HRCT may predict a more favorable clinical course in patients with IPF, supporting the validity of the new IPF diagnostic guidelines.

scholarly journals Different forms of human liver glutathione s-transferases arise from dimeric combinations of at least four immunologically and functionally distinct subunits

1985 ◽  
Vol 232 (3) ◽  
pp. 781-790 ◽  
Author(s):  
S V Singh ◽  
D D Dao ◽  
C A Partridge ◽  
C Theodore ◽  
S K Srivastava ◽  
...  
Keyword(s):  
Human Liver ◽  
Human Lung ◽  
The Other ◽  
Two Dimensional ◽  
Liver Glutathione ◽  
Enzyme Form ◽  
Glutathione S Transferases ◽  
B Subunits ◽  
Subunit Hybridization

Four immunologically distinct subunits were characterized in glutathione (GSH) S-transferases of human liver. Five cationic enzymes (pI 8.9, 8.5, 8.3, 8.2 and 8.0) have an apparently similar subunit composition, and are dimers of 26 500-Mr (A) and 24 500-Mr (B) subunits. A neutral enzyme, pI 6.8, is a dimer of B-type subunits. One of the anionic enzymes, pI 5.5, is also a dimer of 26 500-Mr subunits. However, the 26 500-Mr subunits of this anionic enzyme form are immunologically distinct from the A subunits of the cationic enzymes, and have been designated as A'. Immunoabsorption studies with the neutral enzyme, BB, and the antibodies raised against the cationic enzymes (AB) indicate that A and B subunits are immunologically distinct. Hybridization in vitro of the A and B subunits of the cationic enzymes (AB) results in the expected binary combinations of AA, AB and BB. Studies with the hybridized enzyme forms indicate that only the A subunits express GSH peroxidase activity. A' subunits have maximum affinity for p-nitrobenzyl chloride and p-nitrophenyl acetate, and the B subunits have highest activity towards 1-chloro-2,4-dinitrobenzene. The other anionic form, pI 4.5, present in liver is a heterodimer of 22 500-Mr (C) and B subunits. The C subunits of this enzyme are probably the same as the 22 500-Mr subunits present in human lung and placental GSH transferases. The distinct immunological nature of B and C subunits was also demonstrated by immunoaffinity and subunit-hybridization studies. The results of two-dimensional polyacrylamide-gel-electrophoretic analyses indicate that in human liver GSH transferases, three charge isomers of Mr 26 500 (A type), two charge isomers of Mr 24 500 (B type) and two charge isomers of Mr 22 500 (C type) subunits are present.

scholarly journals Clinical Characteristics of Patients with Post-Tuberculosis Bronchiectasis: Findings from the KMBARC Registry

2021 ◽  
Vol 10 (19) ◽  
pp. 4542
Author(s):  
Hayoung Choi ◽  
Hyun Lee ◽  
Seung Ra ◽  
Hyun Kim ◽  
Jae Lee ◽  
...  
Keyword(s):  
Lung Function ◽  
Clinical Characteristics ◽  
Symptom Burden ◽  
The Other ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Severity Scores ◽  
Long Acting ◽  
Post Infectious

The clinical characteristics of patients with post-tuberculosis (TB) bronchiectasis have not been well evaluated. We enrolled 598 patients with bronchiectasis who participated in the Korean prospective bronchiectasis registry and compared the characteristics of post-TB bronchiectasis (19.7%) with post-infectious (19.6%), idiopathic (40.8%), and other (19.9%) bronchiectasis. The patients with post-TB bronchiectasis had a lower body mass index, higher rate of chronic obstructive pulmonary disease, and lower rate of asthma than those in the other groups. The patients with post-TB bronchiectasis had more upper lobe involvement, more severe radiological extent, and worse lung function than those in the other groups. Long-acting muscarinic antagonist/long-acting ß agonist use and mucolytics were more commonly used in the patients with post-TB bronchiectasis than those in the other groups, while inhaled corticosteroid/long-acting ß agonist was less commonly used. There were no significant intergroup differences in bronchiectasis severity scores except for FACED, the number of exacerbations, and quality of life. Post-TB bronchiectasis is characterised by reduced lung function and higher rates of mucolytic use when compared with other bronchiectasis; thus, adequate bronchodilator use and airway clearance techniques may alleviate symptom burden in this population.

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