Analysis of signaling events associated with activation of neutrophil superoxide anion production by eosinophil granule major basic protein

This study was undertaken to identify the signaling events involved in activation of neutrophil superoxide anion (O2-) production by eosinophil granule major basic protein (MBP). MBP did not produce an immediate increase in the cytosolic free calcium concentration ([Ca2+]i), characteristic of phospholipase C activation, but did cause a gradual increase in [Ca2+]i in cytochalasin B-treated cells. Preincubation with 0.01 to 3 micrograms/mL pertussis toxin did not inhibit MBP-stimulated O2- production, and MBP did not stimulate an increase in diradylglycerol levels. MBP did stimulate a low level of phospholipase D activity, as measured by a time-dependent increase in phosphatidic acid and, in the presence of 0.5% ethanol, phosphatidylethanol. Inhibition of MBP-stimulated O2- production by genistein and Western blot analysis using an antiphosphotyrosine antibody showed tyrosine kinase activation by MBP. Calmodulin antagonists (calmidazolium and W-7) caused up to 80% inhibition of MBP- stimulated O2- production. In agreement with the pharmacologic sensitivity, MBP did not stimulate any 51Cr release. These data indicate that tyrosine kinase and calmodulin-dependent steps are involved in the noncytotoxic stimulation of neutrophil O2- production by MBP.     

Allergic characteristics of urban schoolchildren with atopic eczema in Ghana

Background Atopic eczema is an increasing clinical problem in Africa. Objective To determine allergic characteristics and to identify possible risk factors for eczema among schoolchildren in an urbanized area in Ghana. Patients and methods Schoolchildren aged 3–16 years with eczema were recruited. For each patient, one to three age‐ and sex‐matched controls were selected. All children completed a questionnaire and were skin prick tested with a panel of allergens. Blood was drawn to determine the total and allergen‐specific IgE. Conditional logistic regression models with the matching factors included in the model were used to calculate the odds ratios and to adjust for possible confounders. Results A total of 52 children with eczema (27 boys and 25 girls) and 99 controls were included. Levels of total IgE were found to be 9.1 (1.1; 78.4) times more often elevated in children with eczema. This association was mainly driven by elevated IgE levels against cockroach antigen. Children with eczema were found to have 2.0 (0.87; 4.7) times more often positive skin prick tests (SPT), but this association diminished to 1.2 (0.40; 3.6) after adjustment for total IgE levels. Frequent washing with soap was identified as a risk factor for the development of eczema among these children. Conclusion Schoolchildren with eczema in Ghana were characterized by elevated IgE levels especially against cockroach antigen. The association between eczema and positive SPT was much weaker suggesting immune hyporesponsiveness of the skin. After adjustment for IgE level, SPT were less suitable to distinguish children with and without eczema.     

Prognostic implications of ploidy and proliferative activity in the diffuse, aggressive non-Hodgkin's lymphomas

The International Index is a powerful predictor of outcome in the aggressive non-Hodgkin's lymphomas that is based solely on clinical features. Proliferative activity (% S-phase) measured by flow cytometry has been reported to have prognostic significance in many series and may represent a biologic correlate of clinical behavior that further defines prognosis. Flow cytometric analysis of cellular DNA content and proliferative activity (% S-phase) was performed on fixed paraffin- embedded biopsy specimens from 242 previously untreated patients with diffuse, aggressive non-Hodgkin's lymphomas entered on phase III intergroup clinical trials. The International Index was calculated for each patient based on stage, lactate dehydrogenase, performance status, number of extranodal sites, and age, as previously reported. The International Index consistently predicted response to therapy (P = .027) and survival (P = .007) in this series. DNA aneuploidy was shown in 57% of cases, but was not predictive of clinical outcome. The median % S-phase was 9.9 (median coefficient of variation, 3.6%), which was highly correlated with mitotic index (P = .0001). Although a trend associating low proliferative activity with good early survival and very high S-phase with a shortened survival was shown, International Index risk was the only significant predictor of survival in the multivariate analysis. Although proliferative activity quantitated by flow cytometric analysis of nuclei extracted from paraffin-embedded specimens is probably predictive of survival, it is a less powerful prognostic indicator than clinical parameters represented by the International Index and provides no additional prognostic information.     

Immunological responses to respiratory syncytial virus infection in infancy

OBJECTIVES: To determine whether there is evidence of immunological responses in infants with respiratory syncytial virus (RSV) bronchiolitis by measuring inflammatory mediators in peripheral blood and, if found, whether these related to the severity of illness. PATIENTS AND METHODS: Blood was taken from 94 children with RSV infection during the acute episode and 10 or more days later when the child was well. Control serum samples were obtained from well children of similar ages. Serum samples were assayed for mediators of lymphocyte activity (interleukin-4 (IL-4), soluble interleukin-2 receptor (sCD25), soluble intercellular adhesion molecule-1 (sICAM-1), eosinophil activity (eosinophil cationic protein) and neutrophil activity (myeloperoxidase). Symptoms were assessed as very mild (coryza only), mild (symptoms of lower respiratory tract infection), moderate (requiring nasogastric or intravenous fluids), and severe (requiring oxygen or ventilation). RESULTS: IL-4 concentrations were at the lower limits of detection of the assay. The concentrations of sCD-25 were greater in samples from patients with acute illness than from convalescent patients and both were greater than in control samples. sICAM-1 concentrations were similar in samples from patients with acute illness and convalescent patients, but both were greater than in samples from controls. Eosinophil cationic protein concentrations were lower in samples from patients with acute illness than in those from convalescent patients; there was no difference between samples from convalescent and control patients. Myeloperoxidase concentrations were similar in all samples. There was no correlation between the severity of infection and the concentrations of any inflammatory mediators. CONCLUSIONS: There is evidence of an inflammatory response in the peripheral blood of infants with acute bronchiolitis which may affect lymphocytes and eosinophils, but an association between this response and the severity of illness was not shown here.     

Bladder injury in blunt pelvic trauma

Clinical and radiologic findings in 97 patients with bladder injury secondary to blunt pelvic trauma were reviewed. Fifty-five patients had extraperitoneal bladder rupture; 35, intraperitoneal rupture; two, interstitial bladder injury; and five, combined intraperitoneal and extraperitoneal bladder rupture. Of the 61 of 97 patients with film studies available for review, two patients with surgically proved intraperitoneal rupture had false-negative cystograms. In two other cases of intraperitoneal rupture, the diagnosis was established with cystography but was not demonstrated with urography. All cases of extraperitoneal rupture were demonstrated cystographically; in 15 cases in this group, the injury was complex, with extravasation of contrast material beyond the confines of the perivesical space. In two additional patients, incomplete bladder injury termed "interstitial bladder rupture" was identified. A classification of bladder injury based on cystographic patterns of extravasation is proposed.     

Value of chest radiography in excluding traumatic aortic rupture

A retrospective review of chest radiographs from 205 patients with blunt chest trauma who also underwent aortography was performed. Forty-one of the 205 had aortographically proved aortic rupture. Discriminant analysis of 16 radiographic signs indicated that the most discriminating signs were loss of the aorticopulmonary window, abnormality of the aortic arch, rightward tracheal shift, and widening of the left paraspinal line without associated fracture. No single or combination of radiographic signs demonstrated sufficient sensitivity to indicate all cases of traumatic aortic rupture on plain chest radiographs without the performance of a large number of aortographically negative studies. The bedside anteroposterior "erect" view of the chest proved far more valuable than the supine view in detecting true-negative studies. Despite significant reader variability in the interpretation of the various radiographic signs, in general the analysis confirmed the role of chest radiography in this clinical situation, but suggests that its most beneficial use is in excluding the diagnosis and eliminating unwarranted aortography rather than in predicting aortic rupture.