Acute effects of iron-particle radiation on immunity. Part I: Population distributions

Health risks due to exposure to high-linear energy transfer (LET) charged particles remain unclear. The major goal of this study was to confirm and further characterize the acute effects of high-LET radiation ((56)Fe(26)) on erythrocyte, thrombocyte and leukocyte populations in three body compartments after total-body exposure. Adult female C57BL/6 mice were irradiated with total doses of 0, 0.5, 2 and 3 Gy and killed humanely 4 days later. Body and organ masses were determined and blood, spleen and bone marrow leukocytes were evaluated using a hematology analyzer and flow cytometry. Spleen and thymus (but not body, liver and lung) masses were significantly decreased in a dose-dependent manner. In general, red blood cell (RBC) counts and most other RBC parameters were depressed with increasing dose (P < 0.05); the major exception was an increase in cell size at 0.5 Gy. Platelet numbers and volume, total white blood cell counts, and all three major types of leukocytes also decreased (P < 0.05). Lymphocyte populations in blood and spleen exhibited variable degrees of susceptibility to (56)Fe-particle radiation (B > T > NK and T cytotoxic > T helper cells). In the bone marrow, leukocytes with granulocytic, lymphocytic ("dim" and "bright"), and monocytic characteristics exhibited proportional variations at the higher radiation doses in the expression of CD34 and/or Ly-6A/E. The data are discussed in relation to our previous investigations with iron ions, other forms of radiation, and space flight in this same animal model.     

Leukocyte adhesion deficiency II. Advances and open questions

Leukocyte adhesion deficiency II (LAD II) belongs to a group of human congenital diseases in which the interactions of leukocytes with the vascular endothelium are strongly impaired. LAD II is based on a defect in the synthesis of fucosylated glycostructures. This leads to an immunodeficiency owing to the absence of functional selectin ligands and to strong psychomotor defects, as a result of as-yet unknown reasons. In this review we focused on the current controversies, and open questions that have arisen from recent studies on the genetic defect, therapy and the basis of psychomotor defects in LAD II.     

Leukocyte adhesion: High-speed cells with ABS.

In order to decide where to exit blood vessels and enter tissues, leukocytes roll along endothelial surfaces. Recent studies suggest that an 'automatic braking system' (ABS), involving selectin cell-adhesion molecules, enables leukocytes to roll at a fairly constant velocity despite large variations in blood flow rate.     

Genetic models in applied physiology: selected contribution: effects of spaceflight on immunity in the C57BL/6 mouse. II. Activation, cytokines, erythrocytes, and platelets.

This portion of the study quantified the effects of a 12-day space shuttle mission (Space Transport System-108/UF-1) on body and lymphoid organ masses, activation marker expression, cytokine secretion, and erythrocyte and thrombocyte characteristics in C57BL/6 mice. Animals in flight (Flt group) had 10-12% lower body mass compared with ground controls housed either in animal enclosure modules or under standard vivarium conditions (P < 0.001) and the smallest thymus and spleen masses. Percentages of CD25(+) lymphocytes, CD3(+)/CD25(+) T cells, and NK1.1(+)/CD25(+) natural killer cells from Flt mice were higher compared with both controls (P < 0.05). In contrast, CD71 expression was depressed in the Flt and animal enclosure module control mice compared with vivarium control animals (P < 0.001). Secretion of interferon-gamma, IL-2, and IL-4, but not tumor necrosis factor-alpha and IL-5, by splenocytes from Flt mice was decreased relative to either one or both ground controls (P < 0.05). Flt mice also had high red blood cell and thrombocyte counts compared with both sets of controls; low red blood cell volume and distribution width, percentage of reticulocytes, and platelet volume were also noted (P < 0.05) and were consistent with dehydration. These data indicate that relatively short exposure to the spaceflight environment can induce profound changes that may become significant during long-term space missions.     

Exogenous hyalin and sea urchin gastrulation, Part II: hyalin, an interspecies cell adhesion molecule.

The 330 kDa fibrillar glycoprotein hyalin is a well known component of the sea urchin embryo extracellular hyaline layer. Only recently, the main component of hyalin, the hyalin repeat domain, has been identified in organisms as widely divergent as bacteria and humans using the GenBank database and therefore its possible function has garnered a great deal of interest. In the sea urchin, hyalin serves as an adhesive substrate in the developing embryo and we have recently shown that exogenously added purified hyalin from Strongylocentrotus purpuratus embryos blocks a model cellular interaction in these embryos, archenteron elongation/attachment to the blastocoel roof. It is important to demonstrate the generality of this result by observing if hyalin from one species of sea urchin blocks archenteron elongation/attachment in another species. Here we show in three repeated experiments, with 30 replicate samples for each condition, that the same concentration of S. purpuratus hyalin (57 microg/ml) that blocked the interaction in living S. purpuratus embryos blocked the same interaction in living Lytechinus pictus embryos. These results correspond with the known crossreactivity of antibody against S. purpuratus hyalin with L. pictus hyalin. We propose that hyalin-hyalin receptor binding may mediate this adhesive interaction. The use of a microplate assay that allows precise quantification of developmental effects should help facilitate identification of the function of hyalin in organisms as divergent as bacteria and humans.     

The junction between cytokines and cell adhesion.

Several aspects of the interactions between growth factors and cell adhesion are described. Recent advances in the field come from the identification of molecules resembling growth factors or growth factor receptors, which bear cell adhesion motifs as well as molecules participating in both cell growth control and adhesion.     

The limited immunomodulatory effects of escharectomy on the kinetics of endotoxin, cytokines, and adhesion molecules in major burns

Escharectomy has been shown to improve the survival rates and the outcomes in burns. This observational study was conducted to assess the role of escharectomy on the inflammatory mediators in major burns. Seventeen ASA physical status II or status III adult surviving major burn patients were recruited. When the escharectomy was scheduled, a series of blood samples was obtained at -3 and -1 days preoperation, and +1 and +3 postoperation. The changing levels of endotoxin, cytokines, and adhesion molecules were measured with a quantitative sandwich immunoassay. Extensive escharectomy did not appear to have any significant impact on the levels of tumor necrosis factor alpha, interleukin-10, soluble intracellular adhesion molecule-1 and soluble vascular adhesion molecule-1. Meanwhile, endotoxin and E-selectin were significantly decreased after escharectomy. Escharectomy appeared to have a limited immunomodulatory effect on the inflammatory mediators in systemic inflammatory responses induced by major burns. This is probably related to the timing and extent of surgery, and the complex nature of burn-related inflammation.     

Fluidized-bed denitrification for mine waters. Part II: effects of Ni and Co

The dispersion of nitrogenous compounds and heavy metals into the environment is frequent during mining activities. The effects of nickel (Ni) and cobalt (Co) on denitrification of simulated mine waters were investigated in batch bioassays and fluidized-bed reactors (FBRs). At pH 7, batch tests revealed that Co did not exhibit inhibition on denitrification even at 86.6 mg/L. Ni showed to be inhibitory at 50 and 100 mg/L by decreasing nitrate removal efficiencies of 18 and 65 %, respectively. In two FBRs, operated at 7–8 and 22 °C, 5.5 mg/L Ni did not affect nitrate and nitrite removals because of FBR potential of diluting soluble Ni feed concentration. On the contrary, the effluent pH clearly decreased in both FBR1 and FBR2 because of nickel sulfide precipitation and Ni inhibition of the last two steps of denitrification. When Ni injection was stopped, the process recovered more slowly at 22 than 7–8 °C. This is the first study reporting the effect of Ni on denitrification in biological FBRs.     

Ventilatory muscle activation and inflammation: cytokines, reactive oxygen species, and nitric oxide.

Strenuous diaphragmatic contractions that are induced by inspiratory resistive breathing initiate an inflammatory response that involves the elevation of pro- and anti-inflammatory cytokines within the diaphragm, which may then spill into the circulation. The production of reactive oxygen species within working respiratory muscles increases in response to these strenuous diaphragmatic contractions. At the same time, diaphragmatic nitric oxide (NO) production declines significantly, despite a time-dependent increase in NO synthase isoform protein expression. The increase in adhesion molecule expression and infiltration of granulocytes and macrophages that follows may contribute to the contraction-induced diaphragm injury. Enhanced generation of reactive oxygen species, oxidative stress augmentation, reduced NO production, and glycogen depletion are potential stimuli for the cytokine induction that is secondary to strenuous diaphragmatic contractions. This production of cytokines within the diaphragm may contribute to the diaphragmatic muscle fiber injury that occurs with strenuous contractions or to the expected repair process. TNF-alpha is a cytokine that compromises diaphragmatic contractility and may contribute to muscle wasting. IL-6 is a cytokine that may have beneficial systemic effects by mobilizing glucose from the liver and free fatty acids from the adipose tissue and providing them to the strenuously working respiratory muscles. Thus cytokine upregulation within the working diaphragm may be adaptive and maladaptive.     

Leukocyte Elastase Inhibitor, the precursor of L-DNase II, inhibits apoptosis by interfering with caspase-8 activation

LEI (Leukocyte Elastase Inhibitor), the precursor of the pro-apoptotic molecule L-DNase II, belongs to the ovalbumin subgroup of serpins. Several serpins can inhibit apoptosis: the viral serpin Crm A inhibits Fas or TNFalpha-induced apoptosis, and overexpression of PAI-2 or PI-9 protects cells from TNFalpha or granzyme B induced apoptosis. We have previously shown that LEI overexpression protects cells from etoposide-induced apoptosis. The molecular reason of this anti-apoptotic activity is now investigated. We show that, in BHK-21 and HeLa cells, LEI anti-protease activity is essential for its anti-apoptotic effect. The protease inhibited is cathepsin D, released from the lysosome during etoposide treatment. Cathepsin D enhances caspase activity in the cell by cleaving procaspase-8 and LEI overexpression slows down this cleavage, protecting cells from apoptosis. This let us presume that high expression of LEI in tumor cells may reduce the efficiency of etoposide as a chemotherapeutic agent.     

Modification of cellulosic fibers by UV-irradiation. Part II: After treatments effects

This work presents the comparative study on the dyeing behavior of cellulose fibers in alkaline solutions and under the influence of UV radiation. The cellulosic fabrics were pretreated followed by conventional mercerization technique or treatment with UV irradiation. For different time duration the reorganization of cellulose fibers by swelling treatments in alkaline solutions results in numerous structural modifications, causing changes of their accessibility and/or reactivity. The results revealed that the swelling of the cellulosic fibers depends on type of pre-treatment, dose of the radiation and the concentration of alkaline solution used. SEM analysis confirmed that UV irradiation of the cellulosic fibers leads to a higher swelling in comparison with any concentration of NaOH treatment. In comparison of both the treatments, the mercerized cellulosic fibers have shown better tear and tensile strength as compared to the untreated and UV irradiated one. There is adverse effect of UV radiation on the mechanical properties of UV radiation. Moreover, no loss in weight was observed after exposing the cellulose fabrics surface to UV radiation.     

Acute Respiratory Infections in Children: Part II. A Trial of Polyvalent Virus Vaccine

A new polyvalent respiratory virus vaccine has been evaluated in a double-blind trial involving infants and children. Five hundred and sixteen healthy infants and children were given either nine-strain polyvalent respiratory virus vaccine or placebo. The vaccine contained four Influenza strains, three Adenovirus strains and two Parainfluenza strains. Serologic studies revealed that persistent protective antibody levels were achieved with only the Asian Influenza component.The children were followed up clinically for a one-year period and each respiratory illness was recorded. No protection appeared to have been conferred by the vaccine, and indeed a significantly greater number of respiratory illnesses occurred among the vaccinated group.     

Cardiovascular effects of nerve growth factor: An analytical review. Part II

The features of NGF’s influence on the functional activity of the cardiovascular system and the signaling pathways by which activated NGF TrkA and p75 ^ntr receptors regulate the functional state of endothelial and vascular smooth muscle cells and cardiomyocytes are discussed. In addition, the theoretical prospects of agonists and antagonists of TrkA and p75 ^ntr receptors for the treatment of heart and vascular disorders are considered.     

ANG II stimulates phospholipase D through PKCzeta activation in VSMC: implications in adhesion, spreading, and hypertrophy

ANG II stimulates phospholipase D (PLD) activity and growth of vascular smooth muscle cells (VSMC). The atypical protein kinase C-zeta (PKCzeta) plays a central role in the regulation of cell survival and proliferation. This study was conducted to determine the relationship between ANG II-induced activation of PKCzeta and PLD and their implication in VSMC adhesion, spreading, and hypertrophy. ANG II stimulated PKCzeta activity with maximal activation at 30 s followed by a decline in its activity to 45% above basal at 5 min. Inhibition of PKCzeta activity with a myristoylated pseudosubstrate peptide or overexpression of a kinase-inactive form of PKCzeta decreased ANG II-induced PLD activity. Moreover, depletion of PKCzeta with selective antisense oligonucleotides also decreased ANG II-induced PLD activity. Interaction between PLD2 and PKCzeta in VSMC was detected by coimmunoprecipitation. ANG II-induced PLD activity was inhibited by the primary alcohol n-butanol but not the tertiary alcohol t-butanol. The functional significance of PKCzeta and PLD2 in VSMC adhesion, spreading, and hypertrophy was investigated. Inhibition of PKCzeta and PLD2 activity or expression attenuated VSMC adhesion to collagen I and ANG II-induced cell spreading and hypertrophy. These results demonstrate that ANG II-induced PLD activation is regulated by PKCzeta and suggest a crucial role of PKCzeta-dependent PLD2 in VSMC functions such as adhesion, spreading, and hypertrophy, which are associated with the pathogenesis of atherosclerosis and malignant hypertension.     

Regulation of cell adhesion by protein-tyrosine phosphatases: II. Cell-cell adhesion

Cell-cell adhesion is critical to the development and maintenance of multicellular organisms. The stability of many adhesions is regulated by protein tyrosine phosphorylation of cell adhesion molecules and their associated components, with high levels of phosphorylation promoting disassembly. The level of tyrosine phosphorylation reflects the balance between protein-tyrosine kinase and protein-tyrosine phosphatase activity. Many protein-tyrosine phosphatases associate with the cadherin-catenin complex, directly regulating the phosphorylation of these proteins, thereby affecting their interactions and the integrity of cell-cell junctions. Tyrosine phosphatases can also affect cell-cell adhesions indirectly by regulating the signaling pathways that control the activities of Rho family G proteins. In addition, receptor-type tyrosine phosphatases can mediate outside-in signaling through both ligand binding and dimerization of their extracellular domains. This review will discuss the role of protein-tyrosine phosphatases in cell-cell interactions, with an emphasis on cadherin-mediated adhesions.