Surfactant protein B (SP-BThe 8-kDa protein is the result of extensive post-translational processing of a large 381-amino acid precursor within alveolar type 2 cells. Previous studies in cell lines, isolated rat type 2 cells, and human fetal lung (2-7) indicated that processing to the mature 8-kDa protein involves signal peptide cleavage and glycosylation of the C terminus, followed by cleavage of the N terminus and C terminus in succession. We have recently shown that cleavage of the N terminus occurs in two steps, leaving an approximately 10-amino acid remnant flanking mature SP-B which is removed in a final processing step that releases mature SP-B (8). The subcellular location of these processing events and the enzymes necessary for processing SP-B are poorly understood. Previous work by Voorhout and colleagues (9) utilizing immunoelectron microscopy with antisera to mature SP-B and a synthetic pro-SP-B showed pro-SP-B in the endoplasmic reticulum and mature SP-B in lamellar bodies of adult human type 2 cells. Analysis of grain density over other organelles showed intermediate grain densities over multivesicular bodies and Golgi, indicating the involvement of these organelles in SP-B transport and/or processing.The extensive post-translational processing of SP-B is similar to the post-translational processing of the other hydrophobic surfactant protein, SP-C (10 -13). The 21-kDa pro-SP-C undergoes sequential enzymatic cleavages resulting in a 3.7-kDa mature protein. Pro-SP-C is detected in endoplasmic reticulum and a 6-kDa intermediate is enriched in lamellar bodies. Inhibitors of intracellular trafficking and acidification in vitro disrupt all processing beyond the 16-kDa SP-C intermediate. Processing of SP-B and SP-C are linked, since in alveolar type 2 cells of patients with inherited SP-B deficiency SP-C is not processed beyond the 6-kDa intermediate (14,15).In this report, we use epitope-specific antisera and pulsechase labeling studies with inhibitors of protein processing to show that most human pro-SP-B processing is in post-endoplasmic reticulum but pre-lamellar body compartments. Our data extend previous observations of pro-SP-B trafficking and processing to show that early N-terminal propeptide and Cterminal propeptide processing events occur within the Golgi apparatus with processing of the small vestigial N-terminal propeptide domain as a post-Golgi event. We speculate that the N-terminal remnant is involved in trafficking SP-B toward the lamellar body. Previous reports of these data have appeared elsewhere in abstract form (16,17).

Manometric recording from the pyloric channel is challenging and is usually performed with a sleeve device. Recently, a solid-state manometry system was developed, which incorporates 36 circumferential pressure sensors spaced at 1-cm intervals. Our aim was to use this system to determine whether it provided useful manometric measurements of the pyloric region. We recruited 10 healthy subjects (7 males:3 females). The catheter (ManoScan(360)) was introduced transnasally and, in the final position, 15-20 sensors were in the stomach and the remainder distributed across the pylorus and duodenum. Patients were recorded fasting and then given a meal and recorded postprandially. Using pressure data and isocontour plots, the pylorus was identified in all subjects. Mean pyloric width was 2.1 +/- 0.1 cm (95% CI: 1.40-2.40). Basal pyloric pressure during phase I was 9.4 +/- 1.1 mmHg, while basal antral pressure was significantly lower (P = 0.003; 95% CI: 2.4-8.4). Pyloric pressure was always elevated relative to antral pressure in phase I. For phases II and III, pyloric pressure was 7.7 +/- 2.3 mmHg and 9.4 +/- 1.1 mmHg, respectively. Pyloric pressure increased similarly after both the liquid and solid meal. In addition, isolated pressure events and waves, which involve the pylorus, were readily identified.

Background-It was recently shown that the tonic pressure contribution to the high-pressure zone (HPZ) of the esophagogastric segment (EGS) contains contributions from three distinct components, two of which are smooth muscle intrinsic sphincter components, a proximal and a distal component (1).

Longitudinal shortening of the esophagus during peristaltic contraction has been previously analyzed globally using spaced mucosal clips. This method gives a relatively crude measurement. In this study, local longitudinal shortening (LLS) was evaluated using simultaneous high-resolution endoluminal ultrasound (HREUS) and manometry based on basic principles of muscle mechanics. We sought to determine if there are regional differences in LLS of the esophageal muscle during swallow-induced peristaltic contraction and evaluate shortening of the circular smooth muscle (CSM) and longitudinal smooth muscle (LSM) of the esophagus. Twenty normal subjects underwent simultaneous HREUS/manometry at 4 levels (5, 10, 15, and 20 cm above the upper border of the lower esophageal sphincter [LES] high-pressure zone) in the esophagus with 5-mL swallows of water. Ultrasound images were recorded with synchronized manometric pressure data. The images were digitized and the cross-sectional surface area (CSA) of the LSM, CSM, and total muscle (TM) were measured at baseline (at rest) and at peak intraluminal pressure (implying peak CSM contraction) during swallowing. LLS was calculated for the CSM and LSM using the principle of mass conservation, whereby the change in CSA relative to the resting CSA is quantitatively equal to the relative change in length of a local longitudinal muscle segment.CSM, LSM, and TM all shortened longitudinally, with the circular muscle shortening more than the longitudinal muscle, LLS of the CSM and TM layers at 5 cm above the LES was significantly greater than at 20 cm (CSM: 30% difference, P < .001; TM: 18% difference, P < .05). The greater shortening of LSM at 5 versus 20 cm was found not to be statistically significant (11% difference, P > .05). Peak intraluminal pressure strongly correlated with peak muscle thickness of all layers at all levels (r = 0.96-0.98).LLS increases from the proximal to the distal esophagus during bolus transport. CSM and LSM both shorten longitudinally, with CSM shortening more than LSM. The increase in LLS increases the efficiency of peristaltic contraction and likely contributes to the axial displacement of the LES preceding hiatal opening and esophageal emptying.