Several Long-Evans rat substrains carrying the phenotype of oculocutaneous albinism and bleeding diathesis are a rat model of Hermansky-Pudlak syndrome (HPS). The mutation responsible for the phenotype (Ruby) was identified as a point mutation in the initiation codon of Rab38 small GTPase that regulates intracellular vesicle transport. As patients with HPS often develop life-limiting interstitial pneumonia accompanied by abnormal morphology of alveolar type II cells, we investigated lung surfactant system in Long-Evans Cinnamon rats, one strain of the Ruby rats. The lungs showed conspicuous morphology of type II cells containing markedly enlarged lamellar bodies. Surfactant phosphatidylcholine and surfactant protein B were increased in lung tissues and lamellar bodies but not in alveolar lumen. Expression levels of mRNA for surfactant proteins A, B, C, and D were not altered. Isolated type II cells showed aberrant secretory pattern of newly synthesized [ 3 H]phosphatidylcholine, i.e., decreased basal secretion and remarkably amplified agonist-induced secretion.[ 3 H]phosphatidylcholine synthesis and uptake by type II cells were not altered. Thus Rab38-deficient type II cells appear to carry abnormality in lung surfactant secretion but not in synthesis or uptake. These results suggest that aberrant lung surfactant secretion may be involved in the pathogenesis of interstitial pneumonia in HPS.Ruby; Long-Evans Cinnamon rat; alveolar type II cells; lamellar body HERMANSKY-PUDLAK SYNDROME (HPS) is a rare autosomal recessive disorder resulting from abnormal trafficking relating to lysosome-related organelles such as melanosomes, platelet dense granules, and lamellar bodies in alveolar type II cells (10,29). HPS is clinically characterized by oculocutaneous albinism, bleeding diathesis, and, based on its genetic background, additional abnormalities such as progressive interstitial pneumonia. Interstitial pneumonia is the most serious complication arising in patients with HPS and has no effective therapy and is generally fatal by middle age. The lung histology show interstitial pneumonia characterized by enlarged alveolar type II cells that are fulfilled with giant lamellar bodies containing prominently increased surfactant phospholipids (16). It is possible that lung surfactant abnormalities may be closely related to lung pathology in HPS lungs.Several Long-Evans (LE) substrains including Fawn-hooded (FH) and Tester-Moriyama (TM) rats show oculocutaneous albinism and bleeding diathesis and hence are considered to be rat models of human HPS. The responsible gene Ruby was recently identified as Rab38 (18), a member of the Rab small GTPase family that regulates intracellular vesicle transport. A point mutation found in the initiation codon of Rab38 has been assumed to cause null translation of the protein. LE Cinnamon (LEC) rats, which carry ATP7B gene mutation and have been used as a rat model of Wilson disease (31), have also been identified as Ruby rats that harbor the Rab38 mutation (18). Thus Rab38 has been nominated...

BACKGROUND: Spirometry is used to physiologically assess patients with central airway obstruction (CAO) before and after interventional bronchoscopy, but is not always feasible in these patients, does not localize the anatomic site of obstruction, and may not correlate with the patient's functional impairment. Impulse oscillometry may overcome these limitations. We assessed the correlations between impulse oscillometry measurements, symptoms, and type of airway narrowing, before and after interventional bronchoscopy, and whether impulse oscillometry parameters can discriminate between fixed and dynamic CAO. METHODS: Twenty consecutive patients with CAO underwent spirometry, impulse oscillometry, computed tomography, dyspnea assessment, and bronchoscopy, before and after interventional bronchoscopy. The collapsibility index (the percent difference in airway lumen diameter during expiration versus during inspiration) was calculated using morphometric bronchoscopic images during quiet breathing. Variable CAO was defined as a collapsibility index of > 50%. Fixed CAO was defined as a collapsibility index of < 50%. The degree of obstruction was analyzed with computed tomography measurements. RESULTS: After interventional bronchoscopy, all impulse oscillometry measurements significantly improved, especially resistance at 5 Hz, which decreased from 0.67 ؎ 0.29kPa/L/s to 0.38 ؎ 0.17kPa/L/s (P < .001), and reactance at 20 Hz, which increased from -0.09 ؎ 0.11 to 0.03 ؎ 0.08 (P < .001). Changes in dyspnea score correlated with resistance at 5 Hz, the difference between the resistance at 5 Hz and the resistance at 20 Hz, and the reactance at 5 Hz, but not with spirometry measurements. The type of obstruction also correlated with dyspnea score, and showed distinct impulse oscillometry measurements. CONCLUSIONS: Impulse oscillometry measurements correlate with symptom improvements after interventional bronchoscopy. Impulse oscillometry might be useful to discriminate variable from fixed central airway obstruction. (University Hospital Medical Information Network, http://www.umin.ac.jp/english, ID000005322).

Obstructive sleep apnea syndrome is ascribed to pharyngeal dysfunction, but there are only a few reports about the normal morphological values in this anatomical region. We measured the pharyngeal cross-sectional area and the compliance (collapsibility), using the acoustic reflection technique with air breathing, in 181 healthy subjects (age 21–69 years). We assessed their sex-related differences, and the effects of age, body size and body postures on these parameters. The pharyngeal cross-sectional area, defined as the region from the fauces to the glottis, posturally changed with successive decreases in the sitting, left lateral decubitus and supine positions. The area was significantly greater in male than in female subjects in the sitting position (p < 0.01), but no difference was present in the recumbent positions. The pharyngeal cross-sectional area did not correlate with either age or body size. The specific pharyngeal compliance was greater in the males than in the females (p < 0.01) and increased with age only in the male subjects.

Physical and mathematical models were used to study a mechanism that could maintain the layer of pleural fluid that covers the surface of the lung. The pleural space was modeled as a thin layer of viscous fluid lying between a membrane carrying tension (T), representing the lung, and a rigid wall, representing the chest wall. Flow of the fluid was driven by sliding between the membrane and wall. The physical model consisted of a cylindrical balloon with strings stretched along its surface. When the balloon was inflated inside a vertical circular cylinder containing a viscous fluid, the strings formed narrow vertical channels between broad regions in which the balloon pressed against the outer cylinder. The channels simulated the pleural space in the regions of lobar margins. Oscillatory rotation of the outer cylinder maintained a lubricating layer of fluid between the balloon and the cylinder. The thickness of the fluid layer (h), measured by fluorescence videomicroscopy, was larger for larger fluid viscosity (mu), larger sliding velocity (U), and smaller pressure difference (delta P) between the layer and the channel. A mathematical model of the flow in a horizontal section was analyzed, and numerical solutions were obtained for parameter values of mu, U, delta P, and T that matched those of the physical model. The computed results agreed reasonably well with the experimental results. Scaling laws yield the prediction that h is approximately (T/delta P)(microU/T)2/3. For physiological values of the parameters, the predicted value of h is approximately 10(-3) cm, in good agreement with the observed thickness of the pleural space.

No abstract