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.     

Vasopressin-induced taurine efflux from rat pituicytes: a potential negative feedback for hormone secretion

Previous work on the whole neurohypophysis has shown that hypotonic conditions increase release of taurine from neurohypophysial astrocytes (pituicytes). The present work confirms that taurine is present in cultured pituicytes, and that its specific release increases in response to a hypotonic shock. We next show that vasopressin (VP) and oxytocin (OT) also specifically release taurine from pituicytes. With an EC₅₀ of ∼2 n m , VP is much more potent than OT, and the effects of both hormones are blocked by SR 49059, a V_1a receptor antagonist. This pharmacological profile matches the one for VP- and OT-evoked calcium signals in pituicytes, consistent with the fact that VP-induced taurine efflux is blocked by BAPTA-AM. However, BAPTA-AM also blocks the taurine efflux induced by a 270 mosmol l⁻¹ challenge, which per se does not evoke any calcium signal, suggesting a permissive role for calcium in this case. Nevertheless, the fact that structurally unrelated calcium-mobilizing agents and ionomycin are able to induce taurine efflux suggests that calcium may also play a signalling role in this event. It is widely accepted that in hypotonic conditions taurine exits cells through anionic channels. Antagonism by the chloride channel inhibitors 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) and 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) suggests the same pathway for VP-induced taurine efflux, which is also blocked in hypertonic conditions (330 mosmol l⁻¹). Moreover, it is likely that the osmosensitivity of the taurine channel is up-regulated by calcium. These results, together with our in situ experiments showing stimulation of taurine release by endogenous VP, strengthen the concept of a glial control of neurohormone output.     

Levels of analysis in etiological research on schizophrenia

Etiological research spanning domains of inquiry as diverse as social psychology and molecular genetics has identified a number of potential factors that likely contribute to the development and clinical manifestation of schizophrenia. In this article, we first highlight the challenges inherent in developing cogent etiological models that represent both the diversity of suspected causal influences and their mechanisms of action. Then, using our own research program as a heuristic context, we present a general analytical framework for identifying and integrating multiple types of etiologic factors across different levels of analysis in the prediction of schizophrenia. In recognition of the myriad complexities of multifactorial causation, we argue that a multilevel causal perspective is required for the development and advancement of a fully nuanced theory of schizophrenia etiology and pathophysiology.     

Multiple pathways of cell invasion are regulated by multiple families of serine proteases

The complex process of tumor invasion requires the coordinated expression and activity of cell-substratum adhesive interactions and of cell-associated protease systems, which destroy the extracellular matrix (ECM), in order to enable the invading cells to simultaneously grip and destroy the anatomical barriers that control cell spreading. A number of data indicate that such a `grip and go' process may be performed by an enlarging series of cell membrane-associated serine proteases and serine protease receptors, which provide the invasive cells with a functional unit (the protease and its receptor), able to mediate cell-substratum adhesion through specific receptor domains, to proteolytically degrade ECM and to deliver into the cell signals that up-regulate the expression either of the protease/receptor complex, or of other adhesion molecules, such as integrins. There is evidence that some proteases and protease receptor expression are under the control of tumor hypoxia, which is the result of an imbalance in oxygen supply and demand. The urokinase-type plasminogen activator (u-PA) receptor (u-PAR) is under hypoxic control and cooperates with other serine proteases of the blood coagulation pathways that may extravasate in the tumor milieu as a result of hypoxia-simulated increase of vessel permeability. Other serine proteases and their receptors cooperate with the cell-associated fibrinolytic system to promote cell invasion. Among these, tissue factor and its ligand coagulation factor VII, thrombin and its protease-activated receptors, and type II trans-membrane serine proteases seem to play a crucial role. This Review takes into consideration the complex scenario of the single serine proteases and related receptors that are involved in cell invasion, as well as the protease receptor/adhesion molecule interplay which is necessary to focus the cell surface-driven proteolysis where adhesion provides a grip to the invading cell. This revised version was published online in July 2006 with corrections to the Cover Date.     

Activation of group I mGluRs elicits different responses in murine CA1 and CA3 pyramidal cells

The group I metabotropic glutamate receptor agonist DHPG has been shown to produce two major effects on CA3 pyramidal cells at rest: a reduction in the background conductance and an activation of a voltage-gated inward current ( I _mGluR(V)). Both effects contribute to depolarising CA3 pyramidal cells and the latter has been implicated in eliciting prolonged epileptiform population bursts. We observed that DHPG-induced depolarisation was smaller in CA1 pyramidal cells than in CA3 cells. Voltage clamp studies revealed that while DHPG elicited I _mGluR(V) in CA3 pyramidal cells, such a response was absent in CA1 pyramidal cells. Both mGluR1 and mGluR5 have been localised in CA3 pyramidal cells, whereas only mGluR5 has been detected in CA1 pyramidal cells. Using mGluR1 knockout mice, we evaluated whether the absence of an I _mGluR(V) response can be correlated with the absence of mGluR1. In these experiments, DHPG failed to elicit I _mGluR(V) in CA3 pyramidal cells. This suggests that the smaller depolarising effects of DHPG on wild-type CA1 pyramidal cells is caused, at least in part, by the absence of I _mGluR(V) in these cells and that the difference in the responses of CA1 and CA3 cells may be attributable to the lack of mGluR1 in CA1 pyramidal cells.     

Circulating stem cell factor in patients with chronic idiopathic urticaria.

BACKGROUND: The nature of histamine-releasing factors involved in the pathogenesis of chronic idiopathic urticaria (CIU) is still controversial, since functional IgG autoantibodies specific for the high-affinity IgE receptor, Fc(epsilon)RI, can be detected in only 20% of patients showing a strong skin reactivity on the autologous serum skin test. The absence of systemic eosinophilia in CIU patients, along with the increase in mast cells in skin biopsy specimens, suggests a possible role for stem cell factor (SCF), the only cytokine/growth factor known to induce mediator release from human mast cells. OBJECTIVE: To investigate the possible role of SCF as a histamine-releasing factor in patients with CIU. METHODS: The SCF levels were measured in serum samples from 65 patients with CIU who scored strongly positive on the autologous serum skin test; of these patients, 32 had negative results and 33 had positive results on in vitro histamine release assay by a quantitative commercial sandwich immunoassay technique. Serum samples from 40 healthy subjects were used as controls. RESULTS: Serum SCF levels in all 65 CIU patients did not differ from those found in healthy controls. No difference in SCF levels was found between patients with positive and negative results on histamine release assay. CONCLUSIONS: An increase in serum SCF levels does not play a pathogenic role in CIU.     

A new chart to monitor weight gain during pregnancy

A new chart to monitor maternal weight gain during pregnancy is presented. The chart is based on the adequacy of maternal weight for height, as suggested by a modified table of weight for average frame size, and the data were derived from a low-income racially-mixed population living in New York City. A nomogram accompanies the chart and is used to calculate values of percentage of "standard weight" at various gestational ages. The chart establishes a desirable weight near term which is equivalent to 120 percent of "standard weight" for women with a pre-pregnancy weight equal to or lower than 100 percent of "standard weight". For women with pre-pregnancy weight above 100% of "standard weight" the desirable weight near term varies according to the initial weight but includes a minimal weight gain of 7 kg for women with pre-pregnancy weight over 120% of standard. Women who attained or exceeded body weight near term equivalent to 120 percent of "standard weight" in low income populations in the US and Chile delivered infants with significantly higher mean birth weight than those from mothers who did not meet this goal.     

Recurrence of pulmonary embolism during anticoagulant treatment: a prospective study.

The risk of early recurrence of pulmonary embolism in patients with venous thromboembolic disease treated by anticoagulants is not well established. To determine the risk linked to contemporary proximal deep venous thrombosis, a prospective study was organised to give clinical and scintigraphic surveillance to 50 patients with angiographically proved pulmonary embolism plus phlebographically proved proximal deep vein thrombosis during the first 15 days of anticoagulant treatment. Perfusion lung scans were performed initially and on days 3, 7, and 15. Only two patients had a recurrence of pulmonary embolism during this period; both episodes were revealed by new symptoms, and one recurrence was fatal. The systematic performance of angiography in four patients found to have new scintigraphic defects led to the diagnosis of "spurious scintigraphic recurrence" in three of them. It is concluded that (a) adjusted anticoagulant treatment showed an effectiveness of 96% for preventing early recurrence of pulmonary embolism in this group of supposed high risk patients, and (b) in patients with recent pulmonary embolism new defects on systematic perfusion lung scans are not specific indicators of recurrent pulmonary embolism.