Enhanced lung injury and delayed clearance of Pneumocystis carinii in surfactant protein A-deficient mice: attenuation of cytokine responses and reactive oxygen-nitrogen species

Surfactant protein A (SP-A), a member of the collectin family, selectively binds to Pneumocystis carinii and mediates interactions between pathogen and host alveolar macrophages in vitro. To test the hypothesis that mice lacking SP-A have delayed clearance of Pneumocystis organisms and enhanced lung injury, wild-type C57BL/6 (WT) and SP-A-deficient mice (SP-A(-/-)) with or without selective CD4(+)-T-cell depletion were intratracheally inoculated with Pneumocystis organisms. Four weeks later, CD4-depleted SP-A-deficient mice had developed a more severe Pneumocystis infection than CD4-depleted WT (P. carinii pneumonia [PCP] scores of 3 versus 2, respectively). Whereas all non-CD4-depleted WT mice were free of PCP, intact SP-A(-/-) mice also had evidence of increased organism burden. Pneumocystis infection in SP-A-deficient mice was associated histologically with enhanced peribronchial and/or perivascular cellularity (score of 4 versus 2, SP-A(-/-) versus C57BL/6 mice, respectively) and a corresponding increase in bronchoalveolar lavage (BAL) cell counts. Increases in SP-D content, gamma interferon, interleukin-4, interleukin-5, and tumor necrosis factor alpha in BAL fluid occurred but were attenuated in PCP-infected SP-A(-/-) mice compared to WT mice. There were increases in total BAL NO levels in both infected groups, but nitrite levels were higher in SP-A(-/-) mice, indicating a reduction in production of higher oxides of nitrogen that was also reflected in lower levels of 3-nitrotyrosine staining in the SP-A(-/-) group. We conclude that despite increases in inflammatory cells, SP-A-deficient mice infected with P. carinii exhibit an enhanced susceptibility to the organism and attenuated production of proinflammatory cytokines and reactive oxygen-nitrogen species. These data support the concept that SP-A is a local effector molecule in the lung host defense against P. carinii in vivo.     

Spermatocytic seminoma. A clinicopathological and immunohistochemical study of 7 cases

Spermatocytic seminoma is an uncommon tumor, representing less than 1% of the testicular tumors, occurring most often in old patients. We report 7 cases of this entity. The average age at presentation was 66 years. Tumors had a polymorphic appearance with small, intermediate and large cells, and "spireme" figures. They were pure, with no sarcomatous component. In all cases, the tumor was limited to the testis. In the peritumoral tissue, there was no intratubular germ cell proliferation, and no atrophic testis. Immunostaining was negative for all the classical antibodies tested (cytokeratins, PLAP, lymphoid markers), but all the cases expressed c-kit (100%). This membranous positivity was focal in 4 cases, very strong, and diffuse in the 3 others. Spermatocytic seminoma must be recognized, because its favorable evolution in absence of a sarcomatous component. Adequate treatment consists of orchidectomy alone. Positive staining for c-kit may be helpful for the diagnosis of spermatocytic seminoma.     

Aspirin-Interleukin-3 Interrelationships in Patients With Anti-Phospholipid Syndrome

PROBLEM: Previously we reported on the generation of experimental anti-phospholipid syndrome (APS) in mice. These models were employed to evaluate the efficacy of various novel therapeutic modalities including interleukin-3 (IL-3) and low dose aspirin. The efficacy of the latter was found to be interrelated. Low dose aspirin is capable of inhibiting the activity of the enzyme cyclooxygenase which is responsible for the metabolism of arachidonic acid towards the production of prostaglandins. This shifts the metabolism of arachidonic acid to the other pathway and leads to an overproduction of leukotrienes. The leukotrienes act as stimulators of IL-3 production, a positive cytokine in pregnancy which enhances placental and fetal development. In the current study we evaluated the IL-3 levels in pregnant women with APS and expanded our knowledge on the interrelationships between aspirin, arachidonic acid metabolites and IL-3 in the human system. METHODS: IL-3 levels were recorded in the serum of pregnant women with APS and compared to a control pregnant group. In addition peripheral blood mononuclear cells from healthy subjects were incubated with different concentrations of aspirin or with arachidonic acid metabolites (Leukotriene B4, C4 or PGE₂), and IL-3 production in the culture fluids was evaluated. RESULTS: Serum level of IL-3 in pregnant patients with primary APS, APS secondary to SLE and SLE was lower in comparison to the control group. The in vitro studies revealed that only low dose aspirin (10 mg/μl) stimulated IL-3 production while higher doses of the drug failed to induce the cytokine generation. Leukotriene B4 and C4 were stimulatory whereas PGE₂ acted as inhibitor of IL-3 production. CONCLUSIONS: The serum level of IL-3 is decreased to pregnant women with primary or secondary APS. Low dose aspirin is capable of stimulating EL-3 production in vitro most probably through an elevation of leukotriene production, which may explain its beneficial activity in preventing the manifestations of APS.     

Adoptive transfer of dendritic cells from allergic mice induces specific immunoglobulin E antibody in naïve recipients in absence of antigen challenge without altering the T helper 1/T helper 2 balance

Dendritic cells (DCs) are important in the regulation of immune responses and it has been proposed that these cells play an important role in asthma; however, their role in food allergy is still largely unknown. Our aim was to study specific immunoglobulin E (IgE) and immunoglobulin G (IgG) responses in naïve recipients following adoptive transfer of myeloid DCs from allergic and control mice. The phenotypic features and lymphokine production of DCs were also investigated. CD11c ^{+ /hi} B220^? DCs isolated from spleen and Peyer's patches (PP) of cow's milk (CM) allergic and control mice were transferred intravenously (i.v.) into naïve syngeneic recipients, and IgE‐ and IgG‐specific responses were evaluated. Experiments were also carried out to determine the levels of interferon‐γ (IFN‐γ) and interleukin (IL)‐4 produced by splenocytes from naïve recipients following the adoptive transfer, and CD40 ligand (CD40L)‐mediated IL‐10 production by DCs from allergic and control mice. DCs isolated from spleen and PP of allergic mice, but not control groups, induced CM‐specific IgG and IgE antibody production in naïve recipients in the absence of previous immunization, but did not modify the T helper 1 (Th1) and T helper 2 (Th2) balance. Furthermore, although no difference was observed in the expression of canonical DC surface markers, PP DCs from allergic mice produced less IL‐10 than DCs from controls. We interpret these data as showing that DCs play a pivotal role in allergen‐specific IgE responses and that a Th2‐skewed response may not be involved in the early phase of allergic responses. The identification of the mechanisms underlying these events may help to design novel strategies of therapeutic intervention in food allergy.     

Cyclic AMP dependent,constitutive thermotolerance in the adenylate cyclase-deficient cr-1 (crisp) mutant of Neurospora crassa

Summary We investigated the heat shock response of the adenylate cyclase deficient mutant cr-1 (crisp) of Neurospora crassa. This strain was observed to be much more resistant to a lethal temperature of 50 °C than the wild type. This constitutive thermotolerance was absent in cr-1 conidiospores raised on cyclic AMP (cAMP, 2.5 mM) supplemented solid medium, but was partially restored when the conidiospores were germinated at 30 °C, a temperature which fails to induce thermotolerance in the wild-type strain. Two other crisp-like Neurospora mutants, cr-2 and cr-3 which, in contrast to cr-1, contain normal levels of cAMP, did not exhibit the thermotolerance phenomenon observed for cr-1. A cr-1, pe, fl (crisp-microconidial) strain also lacked the ability to tolerate a lethal heat treatment. Our results demonstrate that the adenylate cyclase deficient cr-1 mutant of Neu-rospora crassa expresses a constitutive thermotolerant phenotype as a consequence of its primary genetic defect: low levels of cAMP.     

Emulsion polymerization of butyl methacrylate initiated by 2,2′-azoisobutyronitrile, 1. Kinetics and mechanism

The effect of 2,2′-azoisobutyronitrile (AIBN) on the kinetics and mechanism of emulsion polymerization of butyl methacrylate was studied in the presence of anionic emulsifier disodium dodecylphenoxybenzene disulfonate (Dowfax® 2A1) at 60°C. The ratio between the proportion of the polymerization in monomer droplets and that of the polymerization in the aqueous phase was determined for the overall initial rate of butyl methacrylate polymerization in the region of the increasing polymerization rate (interval I). Using the model of polymerization in discrete particles, the portion of the polymerization in monomer droplets with a diameter of 100 nm in the overall polymerization rate is 24,4%; the portion of the polymerization in the water phase is only 0,022% for a concentration of Dowfax® 2A1 of 5 · 10^?2 mol · dm^?3, and 60,4% and 0,054% for a Dowfax® 2A1 concentration of 1 · 10^?2 mol · dm^?3. The exponent of the emulsifier concentration in the equation for the polymerization rate is 0,56 for interval I and 0,36 for interval II; the exponent for the concentration of AIBN over the conversion range between 0 and 30% is 0,34. For the proposed reaction mechanism it is assumed that 2-cyanoisopropyl radicals, generated from AIBN in the water phase, are responsible for the initiation of polymerization in micelles swollen by monomer and in polymer/monomer particles. Polymer/monomer particles are formed also by co-precipitation of oligomer radicals, which in turn are formed by polymerization of monomer molecules present in the water phase. Polymerization within monomer droplets has no significant influence on the course of emulsion polymerization.     

Health-related quality of life following percutaneous coronary intervention during the COVID-19 pandemic

Quality of Life Research - During the COVID-19 pandemic, widespread public health measures were implemented to control community transmission. The association between these measures and...     

Success of Maternal and Child Health Pipeline Training Programs: Alumni Survey Results

Maternal and Child Health Journal - The Maternal and Child Health (MCH) Pipeline Training Program, promotes development of a diverse health workforce by training undergraduate students from...     

Assessing Health-Related Quality of Life in Children with Coeliac Disease: The Italian Version of CDDUX

We aimed to assess Health-Related Quality of Life (HRQoL) of Italian children and their parents with coeliac disease (CD) using the Coeliac Disease Dutch Questionnaire (CDDUX). The CDDUX underwent a cross-cultural adaptation in a multi-step process, according to international guidelines. A total of 224 children aged between 8–18 years and their parents were prospectively recruited. Cronbach α coefficient was determined as a measure of internal consistency of the questionnaire and inter-children/parent reliability by intraclass correlation coefficient. Univariate and bivariate regression models were used to evaluate correlations between clinical variables and children and parents subclasses of CDDUX and overall mean Paediatric Quality of Life Inventory (PedsQL). The Italian CDDUX proved to be valid and reliable, mean CDDUX total score revealing a neutral evaluation of the quality of life in children 52.6 ± 17.2 and parents 49.5 ± 17.9 (p = 0.07) with strong correlation with PedsQL. The only clinical variable which appeared to affect significantly quality of life both in children and parents was the lower age. A comparison with our results showed remarkable differences in the HRQoL of populations of various nationalities. The Italian version of the CDDUX questionnaire is a simple and reliable tool for assessing the HRQoL in children and adolescents with CD.