Inhibitory effect of pulmonary surfactant proteins A and D on allergen-induced lymphocyte proliferation and histamine release in children with asthma

The role of pulmonary surfactant proteins in the pathogenesis of airway inflammation and the impact on asthma has not been elucidated. This study was designed to examine the effect of surfactant proteins A (SP-A) and D (SP-D) on phytohemagglutinin- (PHA) and mite allergen Dermatophagoides pteronyssinus (Der p)-induced histamine release and the proliferation of peripheral blood mononuclear cells (PBMC) in children with asthma in stable condition (n = 21), asthmatic children during acute attacks (n = 9), and age-matched control subjects (n = 7). The results show that SP-A and SP-D were able to reduce the incorporation of [3H]thymidine into PBMC in a dose-dependent manner. In addition to the intact, native SP-A and SP-D proteins, a recombinant peptide composed of the neck and carbohydrate recognition domain (CRD) of SP-D [SP-D(N/CRD)] was also found to have the same suppressive effect on lymphocyte proliferation. This effect was abolished by the presence of 100 mM mannose (for SP-A) or maltose (for SP-D) in the culture medium, which suggested that the CRD regions of SP-A and SP-D may interact with the carbohydrate structures on the surface molecules of lymphocytes. The inhibitory effects of surfactant proteins on PHA- and Der p-stimulated lymphocyte responses were observed in stable asthmatic children and age-matched control subjects, while only a mild suppression (< 25%) was seen in activated lymphocytes derived from asthmatic children with acute attacks. SP-A and SP-D were also found to inhibit allergen-induced histamine release, in a dose-dependent manner, in the diluted whole blood of asthmatic children. We conclude that both SP-A and SP-D can inhibit histamine release in the early phase of allergen provocation and suppress lymphocyte proliferation in the late phase of bronchial inflammation, the two essential steps in the development of asthmatic symptoms. It appears that SP-A and SP-D may be protective against the pathogenesis of asthma.     

Treatment of advanced gastroesophageal reflux disease with Collis gastroplasty and Belsey partial fundoplication

OBJECTIVE: To examine the factors affecting outcome in patients with advanced gastroesophageal reflux disease. DESIGN: Retrospective analysis. SETTING: University tertiary referral center. PATIENTS: Thirty-seven patients with advanced gastroesophageal reflux disease and no previous antireflux surgery. INTERVENTIONS: Thirty patients underwent Collis gastroplasty for esophageal lengthening and Belsey partial fundoplication. Seven patients with esophageal stricture and global loss of esophageal body motility who underwent primary esophagectomy and reconstruction were used as a comparison group. OUTCOME MEASURES: Symptomatic outcome in all 37 patients was assessed by questionnaire at a median of 25 months (range, 5-156 months) after surgery. In a subset of 11 patients undergoing the Collis-Belsey procedure, outcome was measured using 24-hour pH and results of motility studies. RESULTS: The Collis-Belsey procedure was successful in relieving symptoms of gastroesophageal reflux in 21 (70%) of the 30 patients. The outcome was excellent or good in 16 (89%) of 18 patients who presented with symptoms other than dysphagia, but only in 5 (42%) of 12 patients with dysphagia (P = .01). The outcome was particularly poor if dysphagia was associated with a previously dilated esophageal stricture. Persistent or induced dysphagia was the reason for failure in all but 1 patient. Results of 24-hour esophageal pH studies were returned to normal in 8 (73%) of 11 patients undergoing postoperative evaluation. Contraction amplitudes in the distal esophagus and the prevalence of simultaneous contractions in these segments did not change after the operation. All 7 patients who underwent primary esophagectomy were classified as having an excellent or good outcome and were relieved of their reflux symptoms, including dysphagia. Six of these could eat 3 meals per day and enjoyed an unrestricted diet. CONCLUSIONS: The outcome of the Collis-Belsey procedure in patients with advanced gastroesophageal reflux disease without dysphagia is excellent. It is less so in patients with dysphagia as a preoperative symptom. Esophagectomy can provide a good outcome in patients who have a combination of dysphagia stricture and a profound loss of esophageal motility.     

Comparative efficacy of experimental anthrax vaccine candidates against inhalation anthrax in rhesus macaques

The authors examined the efficacy of Bacillus anthracis protective antigen (PA) combined with adjuvants as vaccines against an aerosol challenge of virulent anthrax spores in rhesus macaques. Adjuvants tested included i) aluminum hydroxide (Alhydrogel), ii) saponin QS-21 and iii) monophosphoryl lipid A (MPL) in squalene/lecithin/Tween 80 emulsion (SLT). Animals were immunized once with either 50 micrograms of recombinant PA plus adjuvant, or with Anthrax Vaccine Adsorbed (AVA), the licensed human anthrax vaccine. The serological response to PA was measured by enzyme linked immunosorbent assay. Lymphocyte proliferation and serum neutralization of in vitro lethal toxin cytotoxicity were also assayed. In all vaccine groups, anti-PA IgM and IgG titers peaked at 2 weeks and 4-5 weeks postimmunization, respectively. Five weeks postimmunization, animals in all vaccine groups demonstrated PA-specific lymphocyte proliferation and sera that neutralized in vitro cytotoxicity. Six weeks after immunization, the animals were challenged by aerosol with approximately 93 LD50 of virulent anthrax spores. Animals were bled daily for 1 week to monitor bacteremia, and deaths were recorded. Anti-PA ELISA titers in all groups of immunized animals were substantially increased 2 weeks after challenge. One dose of each vaccine provided significant protection (> 90%) against inhalation anthrax in the rhesus macaques.     

Genetic relationship between soxRS and mar loci in promoting multiple antibiotic resistance in Escherichia coli

Multiple antibiotic resistance in Escherichia coli has typically been associated with mutations at the mar locus, located at 34 min on the E. coli chromosome. A new mutant, marC, isolated on the basis of a Mar phenotype but which maps to the soxRS (encoding the regulators of the superoxide stress response) locus located at 92 min, is described here. This mutant shares several features with a known constitutive allele of the soxRS gene, prompting the conclusion that it is a highly active allele of this gene. The marC mutation has thus been given the designation soxR201. This new mutant was used to examine the relationship between the mar and sox loci in promoting antibiotic resistance. The results of these studies indicate that full antibiotic resistance resulting from the soxR201 mutation is partially dependent on an intact mar locus and is associated with an increase in the steady-state level of mar-specific mRNA. In addition, paraquat treatment of wild-type cells is shown to increase the level of antibiotic resistance in a dose-dependent manner that requires an intact soxRS locus. Conversely, overexpression of MarA from a multicopy plasmid results in weak activation of a superoxide stress response target gene. These findings are consistent with a model in which the regulatory factors encoded by the marA and soxS genes control the expression of overlapping sets of target genes, with MarA preferentially acting on targets involved with antibiotic resistance and SoxS directed primarily towards components of the superoxide stress response. Furthermore, compounds frequently used to induce the superoxide stress response, including paraquat, menadione, and phenazine methosulfate, differ with respect to the amount of protection provided against them by the antibiotic resistance response.     

Human tumor antigens recognized by T cells

The ability of tumor-reactive T cells to mediate in vivo tumor regression has been demonstrated in murine tumor models and by the clinical responses to adoptive immunotherapy with tumor-infiltrating lymphocytes isolated from human melanomas. Investigations carried out in the past several years have resulted in the isolation of a number of the genes encoding antigens recognized by melanoma-reactive T cells. The ability of these products to serve as tumor regression antigens has now begun to be evaluated in clinical vaccine trials.     

Case 5--1998. Clinical management of patients undergoing concurrent cardiac surgery and pulmonary resection

Cystic fibrosis (CF) is one of the most common autosomal recessive disorders in white populations. Significant regional differences in CF mutations among affected individuals have been reported. We have studied the geographic distribution of the relative frequencies of the three most common Dutch CF mutations, deltaF508, A455E, and G542X, by analyzing data on area of residence of CF patients. Significantly higher relative frequencies of the A455E mutation and the G542X mutation were observed in the South-West and the South-East, respectively. A uniform distribution of relative frequencies was found for the deltaF508 mutation. The results of our study show that, even in a small country such as The Netherlands, certain CF mutations may be more common in one region than in another.