Airborne pollen concentrations and the incidence of allergic asthma and rhinoconjunctivitis in northern Italy from 1992 to 2003.

BACKGROUND: Aeroallergens and the environment play an important role in the pathogenesis of respiratory allergies. In a 12-year study carried out in Northern Italy (geographic area of Parma), the effects of airborne pollen and meteorological conditions on the incidence of allergic asthma and rhinoconjunctivitis were evaluated. PATIENTS AND METHODS: Among 9,060 subjects examined for respiratory pathologies at our Allergy Unit, Parma Hospital, Italy, from 1992 to 2003, only 1,054 positive to only one type of inhalant allergen in the skin prick test were studied, to avoid bias of cross-reactivity. Allergy and clinical aspects were compared with the duration of the pollination period, and peaks and total concentrations of airborne pollen. RESULTS: Our data showed a significantly growing trend of allergy to mites, pets and birch pollen and a significant increase in asthma, and a significantly decreasing trend of positive reactions to grasses and a decrease in rhinoconjunctivitis. At the same time, there was a significant decrease in total pollen counts, concentration peaks and pollination period of grasses. A significant increase was only observed in ragweed and ash-olive total and peak pollen concentrations. CONCLUSIONS: Significant correlations between the increasing incidence in asthma and allergy to mites, pets and birch pollen are shown. The decrease in the total pollen count and concentration peaks of grass pollen was correlated to the decreasing trend of rhinoconjunctivitis. The trend of increasing concentrations of ash-olive and ragweed pollen was not accompanied by an increase in the related allergy.

Acute polyradiculoneuropathy occurring after hymenoptera stings: a clinical case study.

Hymenoptera stings may be responsible for both local and systemic reactions; these can be immediate or delayed, depending on the time between the sting and the development of signs or symptoms. Delayed clinical reactions have been reported, although unusual, due to serum sickness and/or affecting organs or systems generally not involved in the immediate reaction, such as heart, kidneys, central and peripheral nervous systems. This paper describes the clinical and immunological findings in a 51-year-old subject, who, after two stings of paper wasps, the second one after the third venom immunotherapy (VIT) injection, presented immediate large local and systemic allergic reactions which quickly improved after e.v. methylprednisolone administration. About 40 hours later, he developed acute polyradiculoneuropathy with muscle weakness, paresthesia, difficulties in standing up and walking. Skin tests and specific IgE determination showed allergy to paper wasp. The activation, by wasp venom, of peripheral blood mononuclear cells in primary culture, evaluated by tritiated thymidine incorporation proliferation assay, showed an important hypersensitivity to wasp venom. Therefore our results suggest the hypothesis that the polyradiculoneuritis causative etiopathogenetic mechanism might be a delayed immunological response to wasp antigens followed by an allergy-triggered autoimmune reaction, as previously suggested by other authors; they found lymphocytic infiltrates in demyelinization areas and at perivascular levels, by histologic examination of autoptical and bioptical material of patients with nervous system lesions after hymenoptera stings.

Thallium-201 myocardial perfusion imaging in patients with systemic lupus erythematosus.

The cardiovascular system is frequently affected in systemic lupus erythematosus (SLE). The observation of clinical manifestations related to the presence of coronary artery disease has not been frequently documented in young SLE patients. In these patients, the presence of inflammatory or thrombotic vascular lesions is often documented by anatomo-histological studies in the absence of previous clinical manifestations. The purpose of this study was to evaluate the presence of myocardial perfusion defects in SLE patients. The study was carried out in 15 patients without clinical signs of myocardial ischemia, 1 male and 14 females, 24 to 64 years old, with a mean SLE duration of 10.2 +/- 7.5 years. All the patients had normal blood pressure; electrocardiogram and Doppler-echocardiographic analysis showed values in the normal range. All the patients underwent thallium-201 exercise stress imaging repeated 3 hours later at rest, with tomographic SPECT analysis. Exercise test was carried out until submaximal load, without induction of ST segment alterations or symptoms. Scintigraphic scan showed normal thallium-201 SPECT imaging in 11/15 patients, while the other 4 patients had a slight perfusion defect, 3 of them in the inferior segment, in 2 non reversible and in 1 reversible; 1 patient had a non reversible defect in the septal segment. These slight perfusion defects, prevalently non reversible, may sometimes be a false positive imaging. Our results are in contrast with the literature observations concerning the frequent incidence of thallium-201 perfusion defects in SLE patients. In young asymptomatic SLE patients, our study does not report very important data indicating myocardial ischemia and suggesting the presence of significant coronary obstruction or vasculitis.

Downmodulation of ERK activity inhibits the proliferation and induces the apoptosis of primary acute myelogenous leukemia blasts.

MAP kinase/ERK kinase (MEK)-extracellular signal-regulated kinase (ERK) kinases are frequently activated in acute myelogenous leukemia (AML), and can have prosurvival function. The purpose of this study was to induce downmodulation of MEK-ERK activation in AML primary blasts in order to detect the effect on cell cycle progression and on the apoptosis of leukemic cells. We investigated 14 cases of AML with high ERK 1/2 activity and four cases with undetectable or very low activity. After 24 h incubation of the AML blasts with high ERK activity using PD98059 (New England BioLabs, Beverly, MA, USA), a selective inhibitor of MEK1 phosphorylation, at concentrations of 20 and 40 microM, we observed a strong decrease in the levels of ERK1/2 activity. A significant decrease of blast cell proliferation compared with untreated controls was found. In contrast, the proliferation of blast cells that expressed low or undetectable levels of ERK activity was not inhibited. Time-course analysis demonstrated that the downmodulation of MEK1/2, ERK1 and ERK2 dual-phosphorylation was evident even after 3 h of treatment with 20 and 40 microM. The cleavage of poly(ADP-ribose) polymerase (PARP), an early sign of apoptosis, appeared after 18 h of PD98059 treatment at concentrations of 20 and 40 microM in eight of the 14 cases. After 24 h of treatment, cleaved PARP appeared in all 14 cases. Time-course analysis of cell cycle progression and apoptosis showed that PD98059 induced a G1-phase accumulation with low or undetectable levels of apoptosis after 24 h incubation; after 48 and 72 h incubation, a significant increase of apoptosis was observed. Thus, the primary effect of ERK downmodulation was a cell cycle arrest followed by the apoptosis of a significant percentage of the leukemic blasts. The preclinical model of leukemia treatment reported in this paper makes further comment with regard to MEK1 inhibition as a useful antileukemic target, and encourages the conducting of in vivo studies and clinical investigations.

Expression and activation of SHC/MAP kinase pathway in primary acute myeloid leukemia blasts.

INTRODUCTION: We report the results of a study investigating signaling proteins in 26 cases of primary acute myelogenous leukemia. We studied the Shc adaptor proteins p52/p46Shc, which can activate the RAS/Mitogen Activated Protein kinase pathway, p66Shc which is uncoupled from RAS/MAP kinases and the MAP kinase family members Extracellular signal Regulated Kinase (ERK) and c-Jun NH2-terminal protein Kinase (JNK) or Stress Activated Protein Kinase (SAPK). MATERIAL AND METHODS: CD34+ and CD34- fractions of four human normal bone marrow and unfractionated bone marrow samples were investigated. Immunoblottings, immunoenzymatic and in vitro assays were performed. RESULTS: Shc protein isoforms were constitutively expressed in all the AML cases examined. Tyrosine-phosphorylation of p53/p46Shc isoforms were found in CD34+ but not in the majority of CD34- cases. p66Shc isoform was not tyrosine-phosphorylated in CD34-, and was tyrosine-phosphorylated only in some CD34+ cases. Expression and activation of ERK was constitutively present in the majority of AML patients analysed. JNK/SAPK was expressed but not activated in the AMLs examined. Activation occurred after treatment of the leukemic cells by anisomycin, etoposide, and cytarabine. ERK and JNK/SAPK activation were not detectable in the hematopoietic precursors of human normal bone-marrow. CONCLUSION: These data bear implications for the role of Shc-MAP kinase pathway in normal hemopoiesis and AML leukemogenesis.

Human T cell leukemia virus type II increases telomerase activity in uninfected CD34+ hematopoietic progenitor cells.

The aging process of long-term self-renewing hematopoietic stem/progenitor cells is not yet completely understood and recent studies on antiapoptotic cell pathways have demonstrated a close linkage between telomerase activation and Bcl-2 deregulation in human cancer cells. The present work shows that human T cell leukemia virus type II (HTLV-II) Mo virions that have originated from the T cell line (C344), but not from the B cell line (BJAB), are critically involved in mediating survival and growth effects on hematopoietic precursors (represented by both the TF-1 CD34+ cell line and by peripheral blood-derived CD34+ cells) through the maintenance or enhancement of telomerase activity and the induction of bcl-2 expression. In addition, using an interleukin-3-dependent TF-1 cell line, it was demonstrated that IL-3 deprivation was sufficient to influence the levels of telomerase activity and Bcl-2 expression in CD34+ cells. Taken together, these findings suggest that, in appropriate conditions, extended hematopoietic progenitor cell survival and proliferation following HTLV-II exposure depends on a synergistic interaction between up-regulation of Bcl-2 and activation of telomerase activity.

Synthesis, spectroscopic characterization and biological properties of new natural aldehydes thiosemicarbazones.

As part of a research programme aimed at the synthesis of compounds with antiviral, antibacterial and antitumor properties and their spectroscopic characterization, new thiosemicarbazones deriving from natural aldehydes have been investigated. These substances contain in the same molecule both a chain with nucleophilic centres N, S with tubercolostatic activity, and a glycosidic or alkyl moiety (modified glycosides and nucleosides have recently received a great deal of attention in the fields of neoplastic diseases and viral infections). In this paper the synthesis and the characterization of these compounds by means of 1H NMR, IR, and MS techniques is reported. Biological studies have involved both inhibition of cell proliferation and apoptosis tests on human leukemia cell line U937.

Selective expression and constitutive phosphorylation of SHC proteins [corrected] in the CD34+ fraction of chronic myelogenous leukemias.

The BCR/ABL fusion protein is a constitutively active tyrosine kinase that is responsible for the pathogenesis of chronic myelogenous leukemia (CML). Clinically, CML is characterized by a chronic phase (CP) that eventually terminates into a blast crisis (BC). BC transformation is associated with accumulation of CD34+ blasts. We investigated the expression and phosphorylation of Src-homology-2 and collagen-homology domains (SHC) [corrected] proteins in subpopulations of CML primary cells. Shc polypeptides are tyrosine kinase substrates that are constitutively tyrosine-phosphorylated in continuous cell lines of CML origin. High levels of Shc expression were found in the CD34+ cells from CML-BC, CML-CP and normal bone marrow. In contrast, CD34- fractions from CML-CP and normal bone marrow expressed low levels of p46Shc. Shc proteins were constitutively phosphorylated in the CD34+ fractions from CML cells (both CP and BC), but not in normal CD34+ cells. These data bear implications for the role of Shc in normal hemopoiesis and CML leukemogenesis: (a) dramatic changes of Shc expression during terminal differentiation of hemopoietic cells adds a further level of regulation to the signal transduction function of Shc; and (b) constitutive Shc tyrosine-phosphorylation in the rare CD34+ cells of CML-CP might contribute to the selection of this subpopulation during the blast crisis transformation of CMLs.

Human T-cell leukemia virus type II directly acts on CD34+ hematopoietic precursors by increasing their survival potential. envelope-associated HLA class II molecules reverse this effect.

The role of human T-cell leukemia virus type II (HTLV-II) in human lymphoproliferative and hematopoietic abnormalities in which the retrovirus can be isolated is still elusive. Here we show that the C344 T-cell-derived lymphotropic HTLV-II type IIa Mo strain acts directly on CD34+ hematopoietic precursors by rescuing them from apoptosis induced by interleukin-3 (IL-3) deprivation. This effect is viral strain-specific, as it is not observed with the B-lymphotropic HTLV-II type IIb Gu strain, it does not require infection of the hematopoietic precursors, and, interestingly, it is strongly dependent on the infected cellular host from which the virus was derived. Indeed, growth adaptation of the Mo strain to the permissive B-cell line, BJAB, renders the virus no longer capable of mediating the antiapoptotic effect. However, pretreatment of the BJAB-adapted Mo strain with antibodies specific for HLA class II, but not class I, histocompatibility antigens restores the antiapoptotic potential of the virus. These results constitute the first evidence that HTLV-II retrovirus can directly influence the homeostasis of human progenitors, without infecting them, and that this crucial activity is strongly inhibited by the presence of host-derived envelope-associated HLA class II antigens.

Acenaphthenequinone thiosemicarbazone and its transition metal complexes: synthesis, structure, and biological activity.

The reaction of iron, nickel, copper, and zinc chlorides or acetates with acenaphthenequinone thiosemicarbazone, Haqtsc leads to the formation of novel complexes that have been characterized by spectroscopic studies (NMR, IR) and biological properties. The crystal structures of the free ligand Haqtsc 1 and of the compound [Ni(aqtsc)2].DMF 2, have also been determined by X-ray methods from diffractometer data. In 1, the conformation of the two nonequivalent molecules is governed by intramolecular hydrogen bonds, while an intermolecular hydrogen bond is responsible for dimer-like groups formation. In 2, the coordination geometry about nickel is distorted octahedral, and the two ligand molecules are terdentate monodeprotonated. Biological studies have shown that, for the first time at least up the used doses, a free ligand is active both in the inhibition of cell proliferation and in the induced differentiation on Friend erythroleukemia cells (FLC).

Safety and efficacy of sublingual rush immunotherapy with grass allergen extracts. A double blind study.

Thirty-four patients suffering from rhinoconjunctivitis with or without asthma due to grass pollen, were submitted to sublingual immunotherapy according to a double blind placebo controlled experimental plan; eighteen patients received the active therapy, sixteen the placebo. A rush preseasonal treatment schedule was followed in order to reach the maintenance dose in 15 days with two administrations per day; the top dose reached was then administered three times a week until the end of the pollen season. The symptoms and drugs related to rhinoconjunctivitis and asthma were recorded by means of diary cards and grass pollen counts were performed during the season. The actively treated group showed a reduction of symptoms of rhinoconjunctivitis and asthma and a lower intake of drugs for the same symptoms; all these differences resulted to be statistically significant. No patient showed local or systemic side effects of any relevance. According to these results of our study, sublingual rush immunotherapy is clinically effective and because of the ease of handling, the shortness of the treatment, the absence of relevant side effects and the high compliance of the patient can be considered as an alternative to classic injective immunotherapy in grass pollen allergic patients.

2,6-diacetylpyridine bis(thiosemicarbazones) zinc complexes: synthesis, structure, and biological activity.

The reaction of zinc chloride, acetate, or perchlorate with two bis(thiosemicarbazones) of 2,6-diacetylpyridine [H2daptsc = 2,6-diacetylpyridine bis(thiosemicarbazone) and H2dapipt = 2,6-diacetylpyridine bis(hydrazinopyruvoylthiosemicarbazone)] leads to the formation of four novel complexes that have been characterized by spectroscopic studies (NMR, IR) and biological properties. The crystal structures of the two compounds--[Zn(daptsc)]2.2DMF (1) and [Zn(H2dapipt)(OH2)2](CIO4)2.3H2O (2)--also have been determined by x-ray methods from diffractometer data. Compound (1) is dimeric and the two zinc atoms have a distorted octahedral coordination. The ligand is deprotonated. In compound (2), the coordination geometry about zinc is pentagonal--bipyramidal and the ligand is in the neutral form. The molecular structure of (2) consists of cations [Zn(H2dapipt)(OH2)]2+, CIO4- disordered anions, and three water molecules of solvation. Biological studies have shown that the ligands and the complexes Zn(daptsc).1/2EtOH and Zn(H2daptsc)Cl2 have an effect in vitro on cell proliferation and differentiation (inhibition); both are concentration dependent. [Zn(daptsc)]2.2DMF (1) shows the effects at lower concentration values with respect to other compounds.

[Critical myocardial ischemia in systemic lupus erythematosus. Case report]. / Ischemia miocardica critica in corso di lupus eritematoso sistemico. Descrizione di un caso clinico.

We present the clinical case of a 26-year-old woman, suffering systemic lupus erythematosus for 15 years, who suddenly had coronary heart disease with angina pectoris on mild effort. Thallium 201 exercise test demonstrated clearcut anteroseptal and apical perfusion defects, whereas repeated echocardiography showed a hypokinetic anteroseptal segment; ECG also reported new Q wave in lead V4. After stronger corticosteroid and immunosuppressive treatment, angina pectoris attenuated and perfusion defects disappeared within few months. We hypothesize a coronary artery vasculitis in the course of systemic lupus erythematosus, probably associated with early coronary artery atherosclerosis.

[Allergic bronchopulmonary aspergillosis; an important cause of asthma sometimes ignored]. / Aspergillosi broncopolmonare allergica: un'importante causa di asma a volte ignorata.

The Authors describe a clinical case of allergic bronchopulmonary aspergillosis that remained unrecognized for a long time. The pathogenetic role of the environment, home climatology, and familiarity is considered. A possible therapeutic approach involving the use of associations of steroids and ketoconazole is also discussed. The Authors would like to draw the attention of physicians to forms of bronchial asthma with eosinophilia.

[Study of pollen of allergologic significance in the urban atmosphere of Parma in the years 1983-1984]. / Studio di alcuni pollini di interesse allergologico nell'atmosfera urbana di Parma negli anni 1983-1984.

From 1983 to 1984 pollen air samples from Parma's urban atmosphere were collected weekly by means of a Burkard recording volumetric spore trap. Data regarding a few of the meteorologic variables were also collected at the same time: temperature, insulation, water precipitation, humidity and wind speed. Some of the more allergenic pollens and their concentration/m3 air were determined from the collected samples: Graminea, Urticaceae, Fagaceae, Salicaceae and Betulaceae. Looking at the results from the period of study, it can be seen that Graminea and Urticaceae were the most represented in comparison with the other families. Graminea was most represented in May 1983, in June 1984 and during the first week of September 1984; Urticaceae in September 1983, May 1984 and September 1984. These pollen concentrations were also compared to the meteorologic data.

HLA-DR antigens and anticardiolipin antibodies in northern Italian systemic lupus erythematosus patients.

Eighty systemic lupus erythematosus (SLE) patients attending 3 clinical centers were evaluated immunologically and immunogenetically. No HLA class II antigens were found to be significantly associated with SLE in these patients. A highly significant (P = 6.17 x 10(-7) association was observed between anticardiolipin antibodies and DR7. A lesser association (P less than 0.025) was also observed between DR2 and/or DR3 and anti-Ro (SS-A) antibodies. No relationship was found between any DR antigen and anti-Sm/RNP, anti-double-stranded DNA, or anti-La (SS-B) antibodies.

Evaluation of some immunological parameters in interstitial lung disease by discriminant analysis.

In 37 subjects affected by interstitial lung diseases (19 patients with pulmonary sarcoidosis, 11 with hypersensitivity pneumonitis, 7 with idiopathic pulmonary fibrosis), we have compared by discriminant analysis (Statistical Package for the Social Sciences, version 8.3) 17 biological parameters derived from bronchoalveolar lavage analysis, gallium-67 scanning and lung biopsy. The aim of the study was to analyze the parameters of these three groups by forming one or more linear combinations of the discriminant variables. In particular, we tried to define the ability of such parameters to define these interstitial lung diseases and the relative importance of the data examined. The functions obtained are highly discriminant, so that the three groups are well distinguished among themselves; it means that the variables employed discriminate among the diseases studied. Among the variables considered, differential cell count, immune complex determination, gallium-67 lung scanning have the most important discriminant capacity. Discriminant analysis emphasizes that the three diseases are mediated by different immune mechanisms and underlines the role of each mechanism in determining the disease.

Study of immune complexes in bronchoalveolar lavage fluids.

Immune complexes (IC) were investigated in the bronchoalveolar lavage fluid (BAL) of 5 patients with hypersensitivity pneumonitis (HP), 11 with idiopathic pulmonary fibrosis (IPF) and 16 with sarcoidosis (S) by three different methods: C1Q-BA, KgB, AKgB-MA. Using AKgB-MA, it is possible to identify the class of antibodies forming the IC. IC were present in all cases of HP, in 8/11 (73%) of IPF and in 10/16 (62%) of S. However, the three tests showed discordant results for the three different diseases: C1Q-BA and KgB-SP were both positive in 40%, AKgB-MA in 80% of HP cases; C1Q-BA in 73%, KgB-SP in 9% and AKgB-MA in 46% of IPF cases; C1Q-BA in 31%, KgB-SP in 12% and AKgB-MA in 31% of S cases. In all of the diseases, the IC were mostly composed of IgG; moreover, in HP IgA was also frequently present. The determination of IC in different fractions obtained from BAL ultracentrifugation, confirmed the simultaneous presence of IC of different molecular weights and antibody composition. Lung transbronchial biopsy with immunofluorescence showed immunoglobulin, prevalently IgG, and C, in all HP cases, the majority of IPF cases and 50% of S cases. This confirms the importance of IC in the pathogenesis and/or evolution of some pulmonary diseases.