Effect of ionenes on structure and catalytic activity of cobaltphthalocyanine, 1. Visible light spectroscopic investigations

The structural behaviour of cobalt(II)phthalocyanine-tetrasodium sulfonate (CoPc(NaSO₃)₄) ( 1 ), a catalyst used in thiol oxidation, was investigated in the presence of ionenes (poly-quaternary ammonium salts), ( 2 ) using visible light spectroscopy. It was observed that ionenes, which have been shown to promote the catalytic activity, strongly enhance the aggregation of the cobalt complex. No cobalt site isolation occurred up to N⁺/Co = 10⁵. Furthermore, a stoichiometric CoPc(NaSO₃)₄/ionene complex appeared to be formed with an N⁺/Co-ratio of 4:1. This ratio was found to hold for ionenes with M?_n varying from 6 100 to 22 000 and charge densities from 0,8 to 1,5. As the charge density was increased, the observed CoPc(NaSO₃)₄ spectrum was more affected. Experiments with oxygen in alkaline solution revealed that the complex was resistant toward oxygen adduct formation in the presence of ionenes. This phenomenon is discussed in relation to the catalytic activity of the system.     

Study of peripheral blood thrombocytes in smokers

Total circulating platelet count and thrombocytogram were examined in 60 tobacco smokers and in 30 nonsmoking normal subjects aged 23-32. The smokers were divided into two subgroups, 30 subjects in each: Group 1 included those with a history of smoking under 5 years and Group 2 those smoking for 5 years and Group 2 those smoking for 6-10 years. The platelet count was found increased in Group 1 smokers at the expense of old, atypical, and involutional forms. In Group 2 smokers the total platelet count and the counts of their differentiation forms were reduced. This evidences the effect of tobacco smoking on circulating platelets, this effect depending on the length of tobacco smoke inhalation.     

Toll-like receptor signaling inhibits structural development of the distal fetal mouse lung.

We tested the hypothesis that innate immune signaling in utero could disrupt the structural development of the fetal lung, contributing to the pathogenesis of bronchopulmonary dysplasia. Injection of Escherichia coli lipopolysaccharide (LPS) into the amniotic fluid of E15 BALB/cJ mice increased the luminal volume density of fetal mouse lungs at embryonic day (E) 17 and E18. LPS also increased luminal volume and decreased distal lung branching in fetal mouse lung explants. This effect required NF-kappaB activation and functional Toll-Like Receptor 4. Airway branching may require fibronectin-dependent epithelial-mesenchymal interactions, representing a potential target for innate immune signaling. Anti-fibronectin antibodies and LPS both blocked distal lung branching. By immunofluorescence, fibronectin localized to the clefts between newly formed airways but was restricted to peripheral mesenchymal cells in LPS-exposed explants. These data suggest that LPS may alter the expression pattern of mesenchymal fibronectin, potentially disrupting epithelial-mesenchymal interactions and inhibiting distal airway branching and alveolarization. This mechanism may link innate immune signaling with defects in structural development of the fetal lung.     

Nucleus A10 dopaminergic neurons in inbred mouse strains: Firing rate and autoreceptor sensitivity are independent of the number of cells in the nucleus

Inbred mouse strains have different numbers of midbrain dopaminergic neurons; for example, BALB/cJ mice have 20–25% more neurons than CBA/J mice. As the number of cells decrease, for example in Parkinson's disease and in animals with midbrain dopaminergic cell lesions, the activity of their remaining cells increases. The purpose of the present experiment was to determine whether the functional properties of dopaminergic neurons in the ventral tegmental area (nucleus A10) differ in inbred mouse strains which possess different numbers of cells. The firing rate and autoreceptor sensitivity of A10 dopaminergic cells were examined in the in vitro slice preparation in BALB/cJ, C3H/HeJ, CBA/J, and DBA/2J mouse strains. It was observed that the autoreceptors on mouse dopaminergic neurons exhibit pharmacological properties of dopamine autoreceptors; activation of the autoreceptor produced a marked inhibition (50–70%) in cell firing rate by quinpirole (10⁻⁸ M), LY-141865 (10⁻⁷ M), (+)-3-(3-hydroxyphenyl)-N-n-propyl-piperidine (10⁻⁶ M), propyl-norapomorphine (10⁻⁵ M) and dopamine (10⁻⁴ M), and this inhibition was blocked or reversed by specific dopamine D2 receptor antagonists [(−) sulphide and spiroperidol, 10⁻⁶ M]. The baseline firing rates of the A10 cells did not differ among the four inbred strains [range 2.5 ± 0.2 (C3H/HeJ)−3.4 ± 0.3 (CBA/J) spikes/s ±SEM], and there was no significant difference in autoreceptor sensitivity among the mouse strains as assessed either by superfused dopamine (inhibitory dose 50% ≈150 μM), or by superfused quinpirole (inhibitory dose 50% ≈10 nM). These data indicate that differences in A10 cell numbers of 30% do not significantly influence the baseline firing rate or autoreceptor sensitivity of the cells.     

A novel mutation in the last exon of ATRX in a patient with α-thalassemia myelodysplastic syndrome

Abstract:  We describe a patient with acquired alpha-thalassemia myelodysplastic syndrome (ATMDS). A previously healthy 66-year-old man presented with hemoglobin of 9.3 g/dL, mean corpuscular volume 59 fL, and a bone marrow aspirate with increased erythroid precursors and hypolobulated megakaryocytes. Hemoglobin H inclusions were seen in most red cells after 1% brilliant cresyl blue supravital stain of the peripheral blood. At the molecular level, we identified of a novel mutation in the most 3' exon of the ATRX gene ( C GA→ T GA substitution in codon 2407) resulting in a premature termination codon (p.R2407X). This case provides further evidence for a link between ATRX mutations and ATMDS, and suggests a possible role for the conserved Q-box element in ATRX function.     

Effects of IFN-gamma and interleukin-1beta on major histocompatibility complex antigen and intercellular adhesion molecule-1 expression by 9L gliosarcoma: relevance to its cytolysis by alloreactive cytotoxic T lymphocytes.

To enhance the efficacy of cellular immunotherapy for gliomas, we tested the concept of using proinflammatory cytokine treatment with interferon-gamma (IFN-gamma) or interleukin-1beta (IL-1beta) or both to render glioma cells more susceptible to cytolysis by alloreactive cytotoxic T lymphocytes (aCTL). The cytokines, separately or in combination, were able to upregulate major histocompatibility complex (MHC) class I antigen or intercellular adhesion molecule-1 (ICAM-1) on Fischer rat 9L gliosarcoma cells. 9L cells were incubated in vitro for 24, 48, or 72 h with varying concentrations of rat IFN-gamma (0-2000 U/ml) or recombinant human IL-1 (rHUIL-1) (0-1000 U/ml) or both. By 48 h, IFN-gamma (500 U/ml) maximally induced the percentage of positive expressing cells and the relative antigen density of MHC class I and ICAM-1 on 9L cells, whereas IL-1 induced only ICAM-1 expression. Simultaneous incubation of IL-1 with IFN-gamma did not further affect the induction of class I on 9L cells more than that achieved with IFN-gamma alone. 9L cells with upregulated MHC class I and ICAM-1 expression were more sensitive to lysis by aCTL in in vitro cytotoxicity assays, regardless of whether the precursor aCTL came from naive or from 9L-immunized rats. Furthermore, inhibition of 9L cytotoxicity in assays that included blocking antibodies to MHC class I or to ICAM-1 revealed that T cell receptor (TCR) interactions with MHC class I and that ICAM-1 interactions with lymphocyte function-associated-1 (LFA-1) antigen account for a portion of the glioma lysis by aCTL.     

Comparison of bronchial responsiveness to histamine in asthma, allergic rhinitis and allergic sensitization at the age of 7 years

BACKGROUND: Bronchial responsiveness (BR) to histamine or methacholin is a common finding in adult non-asthmatic patients with allergic rhinitis. OBJECTIVE: We tested whether BR is also present in children with a comparatively short history of allergic rhinitis in a paediatric cohort. METHODS: We performed pulmonary function tests and histamine challenges in a total of 654 children (age 7 years, participants of the German Multicenter Allergy Study) and compared PC20 FEV1 values in children with asthma, allergic rhinitis, asymptomatic allergic sensitization and non-atopic controls. RESULTS: Most pronounced BR to histamine was observed in allergic asthmatics (n = 28), irrespective of the presence or absence of allergic rhinitis. Furthermore, PC(20)FEV(1) values in non-asthmatic children with allergic rhinitis (n = 24) were not significantly different from those seen in asymptomatic atopic (n = 54) or non-atopic controls (n = 92). CONCLUSIONS: In contrast to adult study populations, 7-year-old non-asthmatic children with allergic rhinitis do not show a higher degree of BR than asymptomatic atopic or non-atopic controls. Therefore, secondary preventive measures in non-asthmatic children with allergic rhinitis (such as regular local anti-inflammatory therapy or specific immunotherapy) should be studied and applied more intensely to prevent bronchial hyper-responsiveness (BHR) and asthma in this high-risk group.