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In association with respiratory tract infections, infants may have episodes of wheezing, which represent the onset of asthma in some of them. Activated eosinophils play a central part in asthmatic inflammation.We investigated whether, in infants experiencing their first episode of wheezing, eosinophil activation is present and can predict the development of asthma.In a prospective trial, eosinophil activation was measured by eosinophil cationic protein (ECP) concentrations in serum from 33 nonatopic infants with their first episode of wheezing, 15 nonatopic infants with upper respiratory tract infection without wheezing, and 18 healthy nonatopic infants. One year later, the children were re-evaluated for a diagnosis of infantile asthma.Wheezing infants had higher median serum ECP levels (13.4 micrograms/L) than children with nonwheezy respiratory tract infection (7.6 micrograms/L, p0.005) or healthy subjects (7.1 micrograms/L, p0.005). In addition, wheezing infants (n = 13) with serum ECP concentrations greater than 20 micrograms/L were more likely to have asthma within 1 year than patients with ECP levels less than 20 micrograms/L (odds ratio = 12.4; confidence interval, 4.6-33.5).Eosinophil activation measured by serum ECP is present in infants with their first episode of wheezing illness, especially in those infants in whom asthma subsequently develops within 1 year. These data may indicate a predictive value of serum ECP measurements in children with wheezing to identify those patients in whom infantile asthma is developing. These findings probably also indicate that serum ECP may be used to identify the children who need early antiinflammatory treatment.

Using a stepwise logistic regression analysis, we investigated clinical data, allergologic findings, spirometric data, and the cellular and humoral immune system in order to gain new insights into the role these parameters play in bronchial hyperresponsiveness to methacholine in children and to create a model for the prediction thereof. Bronchial hyperresponsiveness, which was found in 124 of 462 children (26.8%), was observed to have been influenced by an increased level of eosinophils, the positivity of the skin prick test for any of the allergens tested, a decreased baseline forced expiratory volume in 1 second (FEV 1 ) (percent predicted), a decreased maximum expiratory flow at 50% expiration as a percent of forced vital capacity, and a decreased level of κ-chain-assembled immunoglobulins. Logit analysis disclosed that the influence of all other parameters on the occurrence of bronchial hyperresponsiveness was of no further statistical significance. The degree of bronchial hyperresponsiveness (provocative dose causing a 20% fall in FEV 1 ) showed a statistically significant correlation with the eosinophil count (Spearman's r = −0.198) and FEV 1 (percent predicted) (Spearman's r = 0.203). Our findings suggest that allergic sensitization and eosinophilic reaction in children are major factors in contributing to the occurrence of bronchial hyperresponsiveness to methacholine.

The VITROS 5,1 FS analytical system was evaluated. The measurement of the serum proteins and HDL cholesterol with the newly developed MicroTip technology was compared with other nephelometric and turbidimetric methods. The within-run imprecision for apolipoprotein A1, apolipoprotein B, complement 3, complement 4, transferrin, immunoglobulin A, immunoglobulin M, immunoglobulin G and HDL cholesterol showed coefficients of variation between 0.4% and 4.7%. The day-to-day imprecision showed coefficients of variation between 0.5% and 4.0%. The correlation with the comparative methods (nephelometric or turbidimetric) was good, with Pearson correlation coefficients of between 0.959 and 0.995. The comparison of apolipoprotein Al showed a slope of about 0.76. An explanation for the difference could not be found. The VITROS 5,1 FS analytical system is a reliable routine instrument which fits into a large pediatric laboratory of a university.

Antiproteinase 3 antibodies (antiPR3) are assumed to be subtypes of antineutrophil cytoplasmic autoantibodies (ANCA), with a high specificity for active Wegener's granulomatosis and microscopic polyangiitis. Thus, antiPR3 positivity in ELISA, together with negativity in indirect immunofluorescence (IIF) is a rare finding. A 56-year-old man with Dupuytren's contracture and polyneuropathy was admitted for leukocytoclastic vasculitis. Echocardiography, performed because of fever and dyspnea, detected aortic valve endocarditis. Because of severe aortic insufficiency the valve was replaced. Blood cultures and bacteriologic investigations of the explanted valve were negative. AntiPR3 were elevated (123-163 U/ml; normal6 U/ml), together with negativity in IIF. This case shows that antiPR3 elevation with negative ANCA may be associated with vasculitis, endocarditis, polyneuropathy and Dupuytren's contracture. A causal relationship between the clinical presentation and antiPR3 elevation is likely. In order not to miss such cases of vasculitis, combined screening by IIF and ELISA is recommended in selected cases.

Activins are dimeric growth factors composed of beta-subunits, four of which have been isolated so far. Whereas activin beta(A) and beta(B) are expressed in many tissues, the expression of activin beta(C) and beta(E) is confined to the liver. To date no biological role or activity has been assigned to activins formed from beta(C) or beta(E) subunits (activin C and E). Because activin A (beta(A)beta(A)), among its various functions in other tissues, appears to be a negative regulator of liver growth, we hypothesized a similar role for activin C and E. Using a nonviral gene transfer system we specifically delivered genes encoding activin beta(C), beta(E), or beta(A) to the mouse liver. The mRNA analysis and reporter gene coexpression both indicated a reproducible temporal and spatial transgene expression pattern. The effects of activin overexpression were studied in the context of a regenerative proliferation of hepatic cells, a result of the tissue damage associated with the hydrodynamics based gene transfer procedure. Activin beta(C), beta(E), or beta(A) expression, all temporarily inhibited regenerative DNA synthesis of hepatocytes and nonparenchymal cells, though to a varying degree. This first report of a biological activity of activin C and E supports an involvement in liver tissue homeostasis and further emphasizes the role of the growing activin family in liver physiology.

Direct gene transfer to mammalian tissues has significant potential for biomedical research and gene therapy. Recently, the efficient transfer of naked plasmid DNA to the mouse liver by a rapid high-volume tail-vein injection was reported. We carried out a systematic analysis of the dose and time dependence of the expression of the Escherichia coli beta-galactosidase gene transferred by this technique. Surprisingly, the DNA concentration of the administered solution determined primarily the cellular gene dose and, hence, the expression of the transgene in individual hepatocytes, while the number of transfected cells was largely independent of the supplied plasmid mass. Transgene expression was transient: after a rapid onset and a peak at 8 h past injection, it gradually declined and was no longer detectable 4 weeks later. Although gene transfer was accompanied by tissue damage and subsequent regenerative proliferation, the decline in transgene expression was not due to increased hepatocyte turnover or to promoter downregulation, but instead cells apparently lost the plasmid DNA. Furthermore, we show that "nakedness" of the injected DNA is indeed a prerequisite for efficient transfer by the hydrodynamics-based procedure. Our data provide important clues for the successful use of this gene transfer technique, and may point directions for studies on the underlying mechanisms.

In previous experimental animal studies it has been demonstrated that antibody depletion is not followed by increased antibody synthesis. To assess whether these results are conferrable to antibody-depleted humans, we measured free light chains (flcs) as markers of current antibody synthesis in 8 patients treated with immunoadsorption (IA) therapy. Specific and bulk immunoglobulin levels were obtained simultaneously. The mean serum flc concentration increased to the preapheresis value within 1 day and remained unchanged thereafter. Total immunoglobulin G (IgG) and specific antibody concentrations increased to pretreatment values in 88% and 43% of the patients, respectively, and remained below the original values in the others. In conclusion, the lack of increased flc synthesis after IA confirms the absence of a feedback mechanism regulating antibody synthesis. The restoration of serum IgG levels after IA, therefore, does not result from increased antibody synthesis but is probably related to changes of catabolism and immunoglobulin backflow.

We investigated the changes in the cellular and humoral immune system in bronchoalveolar lavage (BAL) performed in 22 patients with pulmonary sarcoidosis and in 14 normal control subjects and their interactions with lung function parameters. Lymphocytosis, the increase in OKT4+ lymphocytes and OKT4+OKDR+ lymphocytes correlated with the increase in immunoglobulins, especially IgG, IgA and kappa chain assembled immunoglobulins. The transferrin levels obtained in BAL were found to be higher in patients with sarcoidosis, and they correlated with the cellular and, more closely, with other humoral findings. A negative correlation existed between the ventilatory parameters and the cell count and humoral findings. In addition, we found a negative correlation between the diffusing capacity for carbon monoxide and other cellular findings, which was most pronounced with reference to lymphocytes, OKT4+ lymphocytes and the OKT4+/OKT8+ ratio. These results underscore the role of OKT4+ lymphocytes, activated OKT4+OKDR+ lymphocytes and transferrin in the increase in immunoglobulins, mainly kappa chain isotypes. Because of the relationship between these changes and ventilatory parameters, and the diffusing capacity, the above results also reveal the clinical relevance of our findings.

To investigate the lasting effects of high ozone concentrations under environmental conditions, we examined the respiratory health, pulmonary function, bronchial hyperresponsiveness to methacholine, allergic sensitization, and lymphocyte subpopulations of 10- to 14-yr-old children. A total of 218 children recruited from an area with high ozone concentrations (Group A) were tested against 281 children coming from an area with low ozone concentrations (Group B). As to subjective complaints, categorized as "usually cough with or without phlegm," "breathlessness," and "susceptibility to chest colds," there was no difference between the two groups. The lung function parameters were similar, but in Group A subjects' bronchial hyperresponsiveness occurred more frequently and was found to be more severe than in Group B (29.4 versus 19.9%, p less than 0.02; PD20 2,100 +/- 87 versus 2,350 +/- 58 micrograms, p less than 0.05). In both groups the number of children who had been suffering from allergic diseases and sensitization to aeroallergens, found by means of the skin test, was the same. Comparison of the total IgE levels showed no difference at all between the two groups. As far as the white blood cells are concerned, the total and differential cell count was the same, whereas lymphocyte subpopulations showed readily recognizable changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Since reports on the influence of melatonin (aMT) on the human endocrine system are scant and inconsistent, the effect of an acute, pharmacological dose of aMT on various hormone levels in healthy males was examined in 3 different experiments. Experiment I: 80 or 240 mg of crystalline aMT were administered per os to 8 volunteers. Before, during and after this treatment, serum levels of aMT, PRL, LH, FSH and testosterone were examined. Although aMT increased at least 1,500-fold over basal levels, only PRL was significantly and consistently elevated after aMT treatment, whereas serum levels of the other hormones were not altered. Experiment II: in 2 subjects, the pulsatile secretion pattern of LH was monitored for 6 h before and 6 h after aMT administration (240 mg p.o.). Neither the amplitude nor the frequency of LH pulses was influenced by the pineal hormone. Experiment III: in 14 volunteers, serum PRL, GH, TSH and cortisol concentrations were examined, once after oral administration of 240 mg aMT and once after placebo. Serum PRL levels were significantly higher after aMT than after placebo; GH showed a slight but not significant trend towards elevation after aMT, whereas other hormones were not altered. An acute pharmacological dose of aMT causes isolated elevation of serum PRL levels and may slightly increase GH. Hormones of the pituitary gonadal axis as well as TSH and cortisol are not altered by aMT.