Lung development in laminin γ2 deficiency: abnormal tracheal hemidesmosomes with normal branching morphogenesis and epithelial differentiation

BACKGROUND: Laminin γ2 (Lamc2), one of the polypeptides in laminin-332 (laminin-5), is prominent in the basement membrane of alveolar walls and airways of developing and adult lung. Laminins are important for lung morphogenesis and based on its localization, a function for laminin γ2 in lung development has been hypothesized. Targeted deletion of the laminin γ2 gene in mice results in skin blistering and neonatal death at 3–5 days after birth due to failure to thrive. METHODS: Examination of lung development in Lamc2-/- mice through 1–2 days postnatal was accomplished by morphometric analysis, lung bud culture, electron microscopy, immunohistochemical and immunofluorescence staining. RESULTS: Compared to littermate controls, Lamc2-/- lungs were similar in morphology during embryonic life. At post-natal day 1–2, distal saccules were mildly dilated by chord length measurements. Epithelial differentiation as evaluated by immunohistochemical staining for markers of ciliated cells, Clara cells, alveolar type I cells and alveolar type II cells did not reveal a difference between Lamc2-/- and littermate control lungs. Likewise, vascular development, smooth muscle cell differentiation, and elastic fiber formation looked similar, as did airway basement membrane ultrastructure. Branching morphogenesis by lung bud culture was similar in Lamc2-/- and littermate control lungs. Since laminin-332 is important for hemidesmosome formation, we examined the structure of tracheal hemidesmosomes by transmission electron microscopy. Compared to littermate controls, Lamc2-/- tracheal hemidesmosomes were less organized and lacked the increased electron density associated with the basement membrane abutting the hemidesmosome. CONCLUSION: These findings indicate that laminin γ2 and laminin-332, despite their prominence in the lung, have a minimal role in lung development through the saccular stage

Phenotype profiling of Modic changes of the lumbar spine and its association with other MRI phenotypes: a large-scale population-based study

BACKGROUND CONTEXT: Modic changes (MC) are associated with low back pain. They represent vertebral endplate and adjacent vertebral marrow changes on magnetic resonance imaging (MRI), classified into three types. Because of small sample sizes, patient cohorts, and limited phenotype assessment, the morphology and involvement of MC and their association with other spinal phenotypes remain speculative. PURPOSE: We addressed and proposed a phenotypic profiling of MC and their relationship with lumbar MRI phenotypes in a large-scale population-based study. STUDY DESIGN/SETTING: A cross-sectional study of the Hong Kong Disc Degeneration Cohort. PATIENT SAMPLE: The study population consisted of 1,546 Southern Chinese volunteers. OUTCOME MEASURES: Topographical and morphological dimensions of MC, presence of disc degeneration (DD) and displacement, and Schmorl nodes were evaluated. METHODS: Axial T1-weighted and sagittal T2-weighted MRIs (3T) were assessed. RESULTS: Females were 62.4% (mean age, 49 years). The overall prevalence of MC was 21.9% (6.3% Type I and 15.5% Type II). Of all MC, 76% were located at the two lowest lumbar levels. Modic changes at the two lowest lumbar levels were more commonly located laterally (p<.001), less commonly anteriorly (p<.001), and were more extensive horizontally (p=.006) but not in vertical height compared with the upper levels. Type I MC were less common in the anterior part (p=.022), larger in size (height p=.004), and affected more likely the whole horizontal plane (p=.016) than Type II MC. Modic changes were associated with disc displacement, Schmorl nodes, and DD at the affected level (all p<.001), and the strength of association increased with the size of the lesion. Type I MC were associated more strongly with disc displacement (p=.008) and DD (p=.022) than Type II MC. CONCLUSIONS: Our large-scale MRI study is the first to definitely note that MC were size- and type-dependently significantly associated with disc pathology and endplate abnormalities. Our phenotype profiling of MC may have clinical utility

Relative accuracy of body adiposity index and relative fat mass in participants with and without down syndrome

Background/Objectives: The body adiposity index (BAI) and relative fat mass (RFM) are anthropometric measures developed to estimate body composition (%Fat). There is limited research validating these methods of body composition assessment in adults with Down syndrome (DS). The aim of this study was to examine the accuracy of the BAI and RFM in a sample of adults with- and without DS. We hypothesize that the RFM would provide greater accuracy than the BAI when estimating %Fat. Subjects/Methods: BAI and RFM were assessed in a sample of adults (n = 235, 50.2% female, 20.0% DS, 23.1 ± 6.7 years). %Fat assessed using dual-energy X-ray absorptiometry served as the criterion method of body composition. Between-group differences were assessed using a two-way (SEX × DS) analysis of variance. Results: BAI overestimated %Fat in men without DS, but underestimated %Fat in women without DS (4.1 ± 4.5%Fat vs. −3.5 ± 4.6%Fat, respectively, p \u3c 0.001). BAI overestimated %Fat in men and women with DS (4.7 ± 7.8%Fat vs. 0.8 ± 7.5%Fat, respectively, p = 0.090). RFM slightly overestimated %Fat in male and female participants without DS, and did not vary by sex (0.9 ± 4.0%Fat vs. 0.2 ± 4.2%Fat, respectively, p = 0.248). RFM underestimated %Fat in men and women with DS, with no differences observed between sexes (−2.1 ± 5.3%Fat vs. −2.2 ± 6.9%Fat, respectively, p = 0.953). Conclusions: The BAI and RFM can be used to estimate body composition in individuals with- and without DS, however, the RFM yields greater accuracy and is recommended when more advanced methods of body composition assessment are unavailable or create unwanted participant burden

Manually defining regions of interest when quantifying paravertebral muscles fatty infiltration from axial magnetic resonance imaging: a proposed method for the lumbar spine with anatomical cross-reference

© 2017 The Author(s). Background: There is increasing interest in paravertebral muscle composition as a potential prognostic and diagnostic element in lumbar spine health. As a consequence, it is becoming popular to use magnetic resonance imaging (MRI) to examine muscle volume and fatty infiltration in lumbar paravertebral muscles to assess both age-related change and their clinical relevance in low back pain (LBP). A variety of imaging methods exist for both measuring key variables (fat, muscle) and for defining regions of interest, making pooled comparisons between studies difficult and rendering post-production analysis of MRIs confusing. We therefore propose and define a method as an option for use as a standardized MRI procedure for measuring lumbar paravertebral muscle composition, and to stimulate discussion towards establishing consensus for the analysis of skeletal muscle composition amongst clinician researchers. Method: In this descriptive methodological study we explain our method by providing an examination of regional lumbar morphology, followed by a detailed description of the proposed technique. Identification of paravertebral muscles and vertebral anatomy includes axial E12 sheet-plastinates from cadaveric material, combined with a series of axial MRIs that encompass sequencing commonly used for investigations of muscle quality (fat-water DIXON, T1-, and T2-weighted) to illustrate regional morphology; these images are shown for L1 and L4 levels to highlight differences in regional morphology. The method for defining regions of interest (ROI) for multifidus (MF), and erector spinae (ES) is then described. Results: Our method for defining ROIs for lumbar paravertebral muscles on axial MRIs is outlined and discussed in relation to existing literature. The method provides a foundation for standardising the quantification of muscle quality that particularly centres on examining fatty infiltration and composition. We provide recommendations relating to imaging parameters that should additionally inform a priori decisions when planning studies examining lumbar muscle tissues with MRI. Conclusions: We intend this method to provide a platform towards developing and delivering meaningful comparisons between MRI data on lumbar paravertebral muscle quality