Giant ragweed specific immunotherapy is not effective in a proportion of patients sensitized to short ragweed: analysis of the allergenic differences between short and giant ragweed

BACKGROUND: Short ragweed and giant ragweed pollen allergens are considered largely cross-reactive, and it is generally believed that 1 species is sufficient for skin testing and immunotherapy. However, in the area north of Milan (a zone widely invaded only by short ragweed), about 50% of patients submitted to injection specific immunotherapy with giant ragweed showed little or no clinical response, but showed an excellent outcome if they were shifted to short ragweed specific immunotherapy. OBJECTIVE: To investigate allergenic differences between short and giant ragweed. METHODS: IgE reactivity to short ragweed of sera from 16 patients allergic to ragweed was assessed by immunoblot before and after absorption with short and giant ragweed. Moreover, 41 ragweed-monosensitive patients underwent skin prick test with both ragweed species. RESULTS: In several cases, preabsorption of sera with giant ragweed extract was unable to inhibit IgE reactivity fully against both a 43-kd allergen and other allergens at different molecular weights in short ragweed. On skin prick test, short ragweed induced larger wheals than giant ragweed in the majority of patients, and 6 of 41 (15%) patients were strongly short ragweed-positive but giant ragweed-negative. The immunoblot with the serum from 1 of these subjects showed a strong IgE reactivity to short ragweed at about 43 kd in the absence of any reactivity to giant ragweed. CONCLUSION: Short and giant ragweed are not allergenically equivalent. Allergenic differences involve both the major allergens Amb a 1-2/Amb t 1-2 and some minor allergens. In patients allergic to ragweed, both diagnosis in vivo and immunotherapy should always be performed by using the ragweed species present in that specific geographic area.     

The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells

We examined whether the synthesis of interleukin-1 or tumor necrosis factor, two cytokines with potent inflammatory activities, is influenced by dietary supplementation with n-3 fatty acids. Nine healthy volunteers added 18 g of fish-oil concentrate per day to their normal Western diet for six weeks. We used a radioimmunoassay to measure interleukin-1 (IL-1 beta and IL-1 alpha) and tumor necrosis factor produced in vitro by stimulated peripheral-blood mononuclear cells. With endotoxin as a stimulus, the synthesis of IL-1 beta was suppressed from 7.4 +/- 0.9 ng per milliliter at base line to 4.2 +/- 0.5 ng per milliliter after six weeks of supplementation (43 percent decrease; P = 0.048). Ten weeks after the end of n-3 supplementation, we observed a further decrease to 2.9 +/- 0.5 ng per milliliter (61 percent decrease; P = 0.005). The production of IL-1 alpha and tumor necrosis factor responded in a similar manner. Twenty weeks after the end of supplementation, the production of IL-1 beta, IL-1 alpha, and tumor necrosis factor had returned to the presupplement level. The decreased production of interleukin-1 and tumor necrosis factor was accompanied by a decreased ratio of arachidonic acid to eicosapentaenoic acid in the membrane phospholipids of mononuclear cells. We conclude that the synthesis of IL-1 beta, IL-1 alpha, and tumor necrosis factor can be suppressed by dietary supplementation with long-chain n-3 fatty acids. The reported antiinflammatory effect of these n-3 fatty acids may be mediated in part by their inhibitory effect on the production of interleukin-1 and tumor necrosis factor.     

Inhibition of human adrenal androgen secretion by ketoconazole

Summary The effect of ketoconazole on adrenal androgen secretion was examined in 15 patients with elevated serum androgens. In a dose of 600 mg per day orally ketoconazole inhibited the biosynthesis of all measured androgens. The mean reduction in serum levels of dehydroepiandrosterone sulfate was 32%, of dehydroepiandrosterone 54%, of androstenedione 52%, and of testosterone 43%; mean serum levels of cortisol only fell by 19%. The reduction in serum androgen levels was first significant 24 h after beginning of treatment and persisted as long as the drug was administered. We conclude that ketoconazole inhibits adrenal androgen biosynthesis more pronouncedly than cortisol biosynthesis. This might be of clinical benefit in the treatment of hirsutism and other states of androgen hypersecretion.Abbreviations CV coefficient of variation - MV mean value - SEM standard error of the mean - f female - m male - K ketoconazole - ACTH adrenocorticotropic hormone - DHEA dehydroepiandrosterone - DHEAS dehydroepiandrosterone sulfate - A androstenedione - T testosterone - F cortisol - P progesterone - H hirsutism - C Cushing's disease - EAS ectopic ACTH syndrome - ATU adrenal tumor     

Immunological properties of the human Goodpasture target antigen.

IgE rheumatoid factor activity was found to be significantly elevated (P less than 0.01) using an ELISA assay when paired synovial fluid and sera from 13 patients with active RA were compared to ten control samples. Synovial fluid IgE RF activity was higher than predicted by diffusion alone in 7/11 (64%) of the RA synovial fluids studied when coefficients of diffusion were determined. The specificity of IgE RF activity as measured by the ELISA was confirmed using immunoaffinity chromatography. Mast cells, obtained by enzymatic dispersion of rheumatoid synovial tissue, were sensitized with sera containing either IgE antibodies directed against ragweed or IgE with RF activity. Histamine was released upon challenge with anti-IgE antibodies (33.2% +/- 11), ragweed antigen E (34.6% +/- 11), or aggregated gamma globulin (47.6% +/- 17.9). No histamine release was observed if antigen challenge occurred in the absence of appropriate sensitization, with C3 anaphylatoxin, or after immunoadsorption of IgE from sera containing IgE RF activity.     

Cytochemische Untersuchungen an Merozoiten von Babesia ovis und Babesia bigemina (Piroplasmidea) in der Zeckenhämolymphe

Zusammenfassung An Merozoiten von Babesia ovis in der Hämolymphe von Rhipicephalus bursa und Merozoiten von Babesia bigemina in der Hämolymphe von Boophilus microplus und Boophilus decoloratus wurden cytochemische Tests auf DNS, RNS, Lipide und Polysaccharide durchgeführt. Der Merozoitenkern ist feulgenpositiv. Die den Kern undifferenzierter Merozoiten kompakt ausfüllende DNS konzentriert sich in differenzierten Formen an der Kernperipherie. Im Cytoplasma ist kein feulgenpositives Material nachzuweisen. RNS ist im gesamten Cytoplasma der undifferenzierten Merozoiten reichlich vorhanden. In differenzierten Merozoiten akkumuliert die hauptsächliche Masse der RNS in Kernnähe und bildet besonders bei B. ovis intensiv pyroninophile perinukleäre Konzentrationen. Nukleoläre RNS war nicht nachzuweisen. In einem Teil der Merozoiten sind Lipide in geringer Menge vorhanden. PAS-positives Material (Glykogen) scheint in den untersuchten Formen zu fehlen.

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A cytochemical study on merozoites of babesia ovis and babesia bigemina (piroplasmidea) in the hemolymph of ticks

Summary Merozoites of Babesia ovis in the hemolymph of Rhipicephalus bursa and of Babesia bigemina in the hemolymph of Boophilus microplus and Boophilus decoloratus were tested cytochemically for DNA, RNA, lipids and polysaccharides. The nucleus of the merozoites is Feulgen positive. In incompletely developed merozoites the nucleus is uniformly packed with DNA. In fully developed merozoites the DNA-material is concentrated in the peripheral zone of the nucleus. No Feulgen positive material was detected in the cytoplasm of the merozoites. Abundant amounts of RNA occur in all of the cytoplasm of incompletely developed merozoites. In fully developed merozoites, most of the RNA-material is concentrated in the vicinity of the nucleus, where intensely stained pyroninophilic areas were observed, especially in merozoites of B. ovis. No nucleolar RNA was detected. Some merozoites contain small amounts of lipids. PAS positive material is obviously absent in the merozoites tested in this study.

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Mit Unterstützung der Deutschen Forschungsgemeinschaft.     

Visuomotor control within a distributed parieto-frontal network

The aim of this functional magnetic resonance imaging study was to investigate differences in visuomotor control with increasing task complexity. Twelve right-handed volunteers were asked to perform their signature under different degrees of visual control: internally generated movement with closed eyes, signing with open eyes, tracking the line of the projected signature forwards, and tracking the line of the projected signature backwards. There was a gradual onset and disappearance of activation within a distributed network. Parietal, lateral and medial frontal brain areas were activated during all conditions, confirming the involvement of a parieto-frontal system. The weight of activation shifted with increasing task complexity. Internally generated movements activated predominantly the inferior parietal lobule and the ventral premotor cortex, as well as the rostral cingulate area, pre-supplementary motor area (pre-SMA) and SMA proper. Opening the eyes reduced SMA and cingulate activation and activated increasingly the occipito-parietal areas with higher task complexity. Visually guided movements produced an activation predominantly in the superior parietal lobule and dorsal premotor cortex. This study bridges human activation studies with the results of neurophysiological studies with monkeys. It confirms a gradual transition of visuomotor control with increasing task complexity within a distributed parieto-frontal network.     

Immunohistochemical localization of neurofilaments and neuron-specific enolase in 29 cases of neuroblastoma.

Twenty-nine neuroblastomas have been examined with the use of rabbit antibodies specific for each of the three neurofilament polypeptides, with a monoclonal antibody specific for the NF-L polypeptide, and with a rabbit antibody specific for neuron-specific enolase. When frozen material was used, all neuroblastomas were positive with the neurofilaments antibodies. When alcohol-fixed paraffin-embedded material was used, neurofilament staining was weaker and the fixation procedure appeared to destroy the epitopes recognized by the NF-L antibodies preferentially. Although all neuroblastomas were positive for neurone-specific enolase, so were two rhabdomyosarcomas, suggesting that NSE is not an appropriate marker to distinguish the different small blue cell tumors of children.     

Structure-activity relationships and effects of platelet-activating factor antagonists in the hetrazepine series

Thieno-triazolo-1,4-diazepines (hetrazepines) antagonize platelet-activating factor (PAF) induced platelet aggregation and inhibit the binding of [3H]-PAF. Introduction of a carboxamide alkyl side chain into the thiophene ring leads to compounds with less affinity to the benzodiazepine receptor and without sedative effects on the central nervous system (e.g., WEB 2086). By ring closure of the side chain, new tetracyclic compounds have been obtained. A parabolic relationship between either [3H]-PAF binding or PAF activity and the bulkiness of the alkyl substituents to the triazolo ring of the hetrazepines or of the bulkiness the 2-acyl moiety of the PAF analogues was found in quantitative structure-activity relationships. This suggests that perhaps the alkyl substituent of the hetrazepines fits the same receptor pocket as the 2-acyl moiety of the PAF agonists.     

Qa-1, a nonclassical class I histocompatibility molecule with roles in innate and adaptive immunity

Qa-1, a nonclassical class I histocompatibility molecule expressed in mice, predominantly assembles with a single nonameric peptide, Qdm, derived from the signal sequence of certain class Ia molecules. The Qa-1/Qdm complex is the primary ligand for CD94/NKG2A inhibitory receptors expressed on a major fraction of natural killer (NK) cells. Cells become susceptible to killing by NK cells under conditions where surface expression of the Qa-1/Qdm inhibitory ligand is reduced. The CD94/NKG2 "missing-self" recognition system serves as mechanism for removing cells that have abnormalities in the intracellular machinery required for assembly and expression of class I-peptides complexes, as a consequence of viral infection, for example. Despite its highly focused peptide-binding specificity, Qa-1 also has a capacity to act as an antigen-presentation molecule for CD8+ T cells. It appears that a small subpopulation of these T cells undergoes positive selection by interaction with Qa-1 in the thymus, and they maintain their specificity for Qa-1 after maturation. The role of these unusual T cells in adaptive immune responses remains to be defined.