Reliability of symptoms in assessing control of gastric acid secretion in patients with Zollinger-Ellison syndrome.

In the present study we explored whether the presence or absence of symptoms could provide a reliable way of assessing the adequacy of control of gastric secretion in patients with Zollinger-Ellison syndrome who were treated medically. Over a 5-yr period, 26 Zollinger-Ellison syndrome patients were entered into a prospective study which examined the presence or absence of symptoms that are associated with gastric hypersecretion, the presence of absence of upper gastrointestinal pathology, and the degree of control of gastric acid secretion. During their last admission, 15 of the 26 patients (58%) were symptomatic, but post-drug gastric acid secretion for the 2 h before the next dose of medication was not significantly different from that in asymptomatic patients. This lack of correlation between the presence or absence of symptoms and post-drug gastric acid secretion was evident for the group as a whole, as well as for 8 to 12 patients who underwent multiple admissions. Of 23 patients who underwent upper gastrointestinal endoscopy of x-ray, or both, on their last admission, 12 had pathology. Post-drug gastric acid secretion was less in patients without pathology than in those with pathology. Furthermore, in patients in whom post-drug gastric acid secretion was less than or equal to 10 mEq/h, the criterion of acceptable control used in this study, pathology did not occur. These findings demonstrate that the presence or absence of symptoms cannot be used to assess the adequacy of medical control of gastric acid secretion in patients with Zollinger-Ellison syndrome. In our opinion, maintenance of post-drug gastric acid secretion less than or equal to 10 mEq/h for the 2 h before the next dose of medication is an acceptable criterion for long-term control of gastric secretion in patients with Zollinger-Ellison syndrome.

Safety of fiberoptic bronchoalveolar lavage in evaluation of interstitial lung disease.

Over a three-year period, 281 fiberoptic bronchoalveolar lavage procedures were performed on 119 individuals with interstitial lung disease and 22 normal volunteers. There were no major complications. Less than 5 percent of the procedures were associated with minor complications including (2.5 percent), pneumonitis (0.4 percent), bleeding (0.7 percent) and bronchospasm (0.7 percent); none of these complications required therapy. Those individuals developing complications had a wide range of physiologic findings; functional tests could not predict which subjects were more likely to develop minor complications associated with lavage. These findings suggest that bronchoalveolar lavage for interstitial disease is a safe procedure associated with minor risks.

Adsorption characteristics of plasma fibronectin in relationship to biological activity.

We studied the adsorption properties of plasma fibronectin (pFN) on wettable tissue culture (TC) dishes and nonwettable bacteriological (BAC-T) dishes in relationship to its biological activity of promoting fibroblast spreading. The binding of pFN to the dish surfaces was found to be very tight and partially resistant to treatments with 1M NaOH, 2% SDS, 8M urea, or 6M guanidine HCl. Only the combination of trypsin (1 mg/ml) followed by 1M NaOH resulted in complete recovery of surface bound material. The amount of surface bound pFN did not directly correlate with its activity when comparing TC and BAC-T dishes. At low concentrations, more pFN adsorbed onto the surfaces of BAC-T dishes than TC dishes, but the adsorbed material was biologically less active on BAC-T dishes. At high concentrations, pFN adsorbed similarly on both dish surfaces reaching a maximum level of 320 ng/cm2 or 4.4 x 10(11) molecules/cm2. The possibility was considered that pFN unfolded into an inactive conformation when adsorbed on BAC-T dishes at a low concentration but that at high concentrations, molecular packing requirements prevented unfolding. Evidence in favor of this hypothesis was the observation that addition of 50 micrograms/ml of serum albumin simultaneously with low pFN concentrations resulted in adsorption of pFN on BAC-T dishes in an active conformation even though the amount of adsorbed pFN decreased. Competition experiments between pFN and other proteins were carried out, and it was found that pFN has a much higher affinity for BAC-T or TC dish surfaces than albumin or fibrinogen. It was also found that mild heat denaturation of albumin increased its affinity for the surface by an order of magnitude.

Spreading of human fibroblasts in serum-free medium: inhibition by dithiothreitol and the effect of cold insoluble globulin (plasma fibronectin).

We have tested the effect of dithiothreitol (DTT) treatment on the initial spreading of human fibroblasts in serum-free medium in tissue culture dishes. Cell spreading was inhibited following treatment of these cells with 10 mM DTT. Inhibition occurred when the cells were treated at 37 degrees C but not at 4 degrees and was reversible metabolically but not by the addition of sulfhydryl oxidizing reagents. The inhibition was overcome when DTT-treated human fibroblasts were plated on cold insoluble globulin (plasma fibronectin)--coated dishes. Under these conditions spreading appeared to be completely normal, including the formation of focal adhesions. Analysis of the fibronectin concentrations in the human fibroblasts following DTT treatment indicated that there was little decrease in the absolute level of activity as determined in a biological assay for BHK cells spreading on culture dishes. Analysis of the fibronectin distribution on the DTT-treated human fibroblasts by indirect immunofluorescence using a specific anti-CIG antiserum revealed that fibronectin was no longer deposited onto the culture dish surfaces. Even when the DTT-treated human fibroblasts spread in the presence of fetal calf serum, the cell fibronectin remained for the most part in a perinuclear location. These results indicate that DTT treatment of human fibroblasts prevents the normal translocation of fibronectin from a perinulear location to the surface of the culture dish. This study further supports our hypothesis that the initial spreading in serum-free medium of fibroblasts from cell strains depends upon secretion of fibronectin onto the culture dish surface.

Initial adhesion of human fibroblasts in serum-free medium: possible role of secreted fibronectin.

Experiments were carried out to test the hypothesis that the initial attachment and spreading of human fibroblasts in serum-free medium occurs to cell fibronectin which has been secretd spread on tissue culture substrata in serum-free medium in 60 min. When potential protein adsorption sites on the substratum were covered with bovine serum albumin before initial human fibroblasts attachment, their subsequent attachment to the substratum was prevented. When substratum adsorption sites were covered immediately after initial attachment, subsequent cell spreading was prevented. The distribution of fibronectin on human fibroblast surfaces during initial attachment and spreading was studied by indirect immunofluorescence analysis using a monospecific anti-cold-insoluble globulin antiserum. The initial appearance (10 min) of fibronectin was in spots over the entire cell surface. Concomitant with human fibroblast spreading, the random distribution of sites disappeared, and most fibronectin was subsequently observed in spots at the cell substratum interface (60 min). A fibrillar pattern of fibronectin appeared later (2-8 hr). The sites beneath the cells could be visualized as footprints on the substratum following treatment of the attached human fibroblasts with 0.1 M NaOH. A second fluorescence pattern of fibronectin secreted on the substratum was characterized by a diffuse halo around the cells and a very faint, diffuse staining elsewhere on the substratum. Another cell type (baby hamster kideny cells) was used to assay biologically for the presence or absence of the factor secreted by human fibroblasts on the substratum. Human fibroblasts were found to secrete an adhesion factor for baby hamster kidney cells into the substratum in a time- and temperature-dependent fashion, and immunological studies indicated that the factor secreted by human fibroblasts was cross-reactive with cold-in-soluble globulin, the plasma form of fibronectin. The conditioning factor secreted by the human fibroblasts was also found to be an attachment and spreading factor for human fibroblasts in experiments measuring human fibroblast adhesion to fibronectin footprints of human fibroblasts. Substratum-adsorbed cold-insoluble globulin was also found to be an attachment and spreading factor for human fibroblasts. Based upon the timing of appearance of conditioning factors on the substratum and the immunofluorescence patterns, it seems that the diffusely organized fibronectin on the substratum constitutes the sites to which cell attachment occurs. The bright spots of fibronectin that appear beneath the cells may represent fibronectin reorganization during cell spreading.