Specific patterns of allergic sensitization in early childhood and asthma & rhinitis risk.

BACKGROUND: Specific patterns of allergic sensitization as well as quantification of the in vitro IgE response in early life may provide relevant clinical insight into future rhinitis and asthma risk. OBJECTIVE: To define relationships among established sensitization to particular aeroallergens, quantitative analyses of allergen-specific IgE levels, pet exposure and sensitization, and asthma and rhinitis risk. METHODS: Children at high-risk for the development of asthma and allergic diseases were enrolled at birth into the Childhood Origins of ASThma (COAST) study. Allergen-specific IgE was assessed at ages 1, 3, 6, and 9 years by fluoroenzyme immunoassay (Unicap(®) 100; Pharmacia Diagnostics). Current asthma and rhinitis were diagnosed at age 6 and 8 years. RESULTS: Sensitization to dog was strongly associated with increased asthma risk (P < 0.0001). Sensitization to perennial compared with seasonal allergens was more strongly associated with asthma risk, while sensitization to seasonal allergens was more closely associated with rhinitis risk. Increased levels of specific IgE to perennial allergens were associated with an increased asthma risk (P = 0.05), while any detectable level of IgE to seasonal allergens was associated with increased rhinitis risk (P = 0.0009). While dog and cat sensitization were both independently associated with increased asthma and rhinitis risk, dog exposure at birth was associated with a reduced risk of asthma, regardless of dog sensitization status during the first 6 years of life (P = 0.05). CONCLUSIONS AND CLINICAL RELEVANCE: Analysing specific patterns of an individual's allergic sensitization profile reveals additional relevant associations with asthma and rhinitis risk as opposed to the information gained from characterizing an individual as 'atopic' by the presence of any demonstrable sensitization alone. Furthermore, protective mechanisms of dog exposure with regards to asthma risk appear to be unrelated to the prevention of sensitization.

Paraoxonase 1, quorum sensing, and P. aeruginosa infection: a novel model.

Pseudomonas aeruginosa is a Gram-negative bacterium which exacts a heavy burden on immunocompromised patients, but is non-pathogenic in a healthy host. Using small signaling molecules called acyl-homoserine lactones (AHLs), populations of P. aeruginosa can coordinate phenotypic changes, including biofilm formation and virulence factor secretion. This concentration-dependent process is called quorum sensing (QS). Interference with QS has been identified as a potential source of new treatments for P. aeruginosa infection. The human enzyme paraoxonase 1 (PON1) degrades AHL molecules, and is a promising candidate for QS interference therapy. Although paraoxonase orthologs exist in many species, genetic redundancy in humans and other mammals has made studying the specific effects of PON1 quite difficult. Arthropods, however, do not express any PON homologs. We generated a novel model to study the specific effects of PON1 by transgenically expressing human PON1 in Drosophila melanogaster. Using this model, we showed that P. aeruginosa infection lethality is QS-dependent, and that expression of PON1 has a protective effect. This work demonstrates the value of a D. melanogaster model for investigating the specific functions of members of the paraoxonase family in vivo, and suggests that PON1 plays a role in innate immunity.

Virus in a parasitoid wasp: suppression of the cellular immune response in the parasitoid's host.

A virus that replicates in the ovary of a parasitoid wasp is injected into the parasitoid's host during oviposition. Successful development of th parasitoid egg within the host depends on the presence of th virus, which acts to suppress the host's immune response (encapsulation) toward the egg. This is an example of obligatory mutualism between a virus and a eukaryotic organism.

Cytogenetic studies with cyclamate and related compounds.

Cyclamate, cyclohexylamine, N-hydroxycyclohexylamine, and dicyclohexylamine can induce chromosomal damage in human leukocyte cultures.

Scanning tunneling microscopy of Fe- and O-sublattices on Fe3O4(100).

We present scanning tunneling microscopy of an octahedral (B) plane terminated (square root of 2 x square root of 2) R45 degrees-reconstructed surface of a natural magnetite (100) crystal. Implementing a W-tip we achieve the same resolution on Fe rows as was reported in the past either with the use of antiferromagnetic tips or on magnetite (Fe3O4) films. We show images of Fe or O sublattices of Fe3O4 with atomic resolution.

A high-resolution core-level photoemission study of the Au/4H-SiC(0001)-([Formula: see text]) interface.

We present a systematic study of different reconstructions obtained after deposition of Au on the [Formula: see text]-4H-SiC(0001) surface. For 1-2 monolayers (ML) Au and annealing temperature T(anneal)∼675 °C, a 3 × 3 reconstruction was observed. For 4 ML Au and T(anneal)∼650 °C, a [Formula: see text] reconstruction appeared, while 5 ML Au annealed at 700 °C reconstructed to give a [Formula: see text] pattern. From the Si 2p and Au 4f core-level components, we propose interface models, depending on the amount of Au on the surface and the annealing temperature. For 1-4 ML Au annealed at 650-675 °C, gold diffuses under the topmost Si into the SiC and forms a silicide. An additional Si component in our Si 2p spectra is related to the interface between the silicide and SiC. For 5 ML Au annealed at 700 °C, silicide is also formed at the surface, covering unreacted Au on top of the SiC substrate. The interface Si component is also observed in the Si 2p spectra of this surface. The key role in [Formula: see text]-4H-SiC(0001) interface formation is played by diffusion and the silicon-richness of the surface.

Mutagenicity of five cyclic N-nitrosamines: assay with Salmonella typhimurium.

The mutagenicity of five cyclic N-nitrosamines was studied with the use of Salmonella typhimurium TA1535 in vitro with and without microsomal activation. The carcinogens nitrosopiperidine and nitrosopyrrolidine required metabolic activation before manifesting mutagenic activity. Nitrosoproline and nitrosohydroxyproline, noncarcinogens, were not mutagenic. Nitroso-3-pyrrolidinol was mutagenic in the absence of microsomes, thereby suggesting a role of hydroxylation in the metabolic activation of nitrosopyrrolidine to an ultimate carcinogenic species.

Buspirone and diazepam in anxiety: a controlled study.

The anxiolytic properties of buspirone were assessed in a 4-week double-blind study in 240 anxious patients, 81 of whom received buspirone, 81 diazepam, and 78 placebo. Patients were required to have scores greater than or equal to 9 on the Covi and greater than or equal to 18 on the Hamilton Rating Scale for Anxiety, and to endorse at least 5 items on a 17-item Anxiety Entry Checklist. Among 212 evaluable patients, those who improved most were married, well-educated females who had both a positive family adjustment and a low level of depression. Diazepam produced relatively equal improvement in females and males. Diazepam seems more effective in reducing somatic symptoms, while buspirone appears more effective in reducing symptoms associated with cognitive and interpersonal problems. Main differences between the drugs were seen in side effect profiles.

Modulation of the lung host response by granulocyte colony-stimulating factor in rats challenged with intrapulmonary endotoxin.

The effects of granulocyte colony-stimulating factor (G-CSF) on the functional activities of circulating and lung-recruited neutrophils (PMNs) and alveolar macrophages (AMs) were studied in rats to further elucidate the mechanisms underlying G-CSF-enhanced pulmonary host defense. Animals received G-CSF or vehicle twice a day for 2 days, followed by an intratracheal challenge with endotoxin or saline. G-CSF up-regulated CD11b/c expression and mean channel fluorescence intensity of phagocytosis in circulating PMNs. G-CSF also enhanced phagocytic activities, reflected by both the percentage of phagocytosis and mean channel fluorescence intensity in lung-recruited PMNs and AMs in intratracheal endotoxin-challenged rats. The endotoxin-induced increase in pulmonary production of tumor necrosis factor-alpha and cytokine-induced neutrophil chemoattractant was not affected by G-CSF pretreatment. These data demonstrate that G-CSF-enhanced pulmonary recruitment of PMNs is primarily based on the effects of G-CSF on the PMNs themselves, rather than the generation of certain chemotactic stimuli, i.e., cytokine-induced neutrophil chemoattractant and tumor necrosis factor-alpha. The enhanced phagocytic activities of lung-recruited PMNs and AMs also augment pulmonary host defenses in G-CSF-pretreated animals.

Role of poliovirus receptors in the spread of the infection.

Although the poliovirus receptor (PVR) has been cloned, lack of knowledge of its precise tissue distribution makes assessment of its role in mediating poliomyelitis difficult. Our recent work demonstrated that PVR is expressed on human monocytes and that primary human blood cells can support PV replication. In the current work, we demonstrate that CD14-positive cells (monocytes) support PV replication but that only a minority (< 10%) of the cells become infected. In other preliminary studies, immunocytochemical analyses of human brain tissue demonstrated the presence of PVR in the olfactory bulb, a tissue thought to not support PV replication. Thus, it appears that some apparently "ectopic" sites of PVR expression may in fact be sites for PV replication, whereas other sites may indeed be restricted. The ability of monocytes to replicate PV may pertain to some unexplained phenomena in PV pathogenesis, such as the specific cell type carrying out the initial round of replication in the gut, sites of extraneural replication and transport of the virus into the CNS. Preliminary studies with monocytes from post-polio syndrome patients showed no difference in the levels of PVR relative to control monocytes. In other preliminary work, PVR was shown to be phosphorylated and its expression on monocytes increased by treatment with gamma-interferon. The normal function of PVR is likely to be involved in monocyte function during immune activation.

Mutagens produced by Alternaria alternata.

Alternariol, alternariol methyl ether and tenuazonic acid, metabolites present in Alternaria alternata cultures, were tested for mutagenicity with Salmonella typhimurium strains TA98 and TA 100. Alternariol methyl ether was weakly mutagenic to strain TA98 (without metabolic activation). Chromatographic separations of A. alternata mycelium extract yielded several fractions mutagenic in the latter system, including the altertoxin I fraction and a purified yellow pigment C20H14O6, which was characterized spectroscopically.

Mutagenicity induced by lyophilization or storage of urine from isoniazid-treated rats.

Urine collected during 24 h after treatment of rats with 90--550 mg/kg isonicotinic acid hydrazide (isoniazid, INH) was after lyophilization, mutagenic for Salmonella typhimurium TA1535. Urine collected directly from bladders of INH-treated rats was not mutagenic, and solutions of INH in water or urine became mutagenic only after lyophilization. In the absence of lyophilization, sterile urine from INH-treated rats became mutagenic after 8--14 days' storage at room temperature.

Mutagenic effect of nialamide on Salmonella typhimurium.

The mutagenicity of an antidepressant drug, nialamide, was studied with Salmonella typhimurium TA1535-8. Nialamied was mutagenic for strain TA1535 in the absence of rat liver extracts.

Calcium and the effects of ultrasound on frog skin.

Therapeutic ultrasound is used to enhance the repair of soft tissue, muscle, etc., and because many of the cellular reactions involved in these processes are dependent on the intracellular availability of free calcium ions, it becomes important to study the effects of ultrasound in the presence and the absence of calcium ions. Using frog skin as a biological model, the effect of therapeutic ultrasound (300 mW/cm2 1 MHz CW) was investigated. Sonication for two minutes caused a significantly larger increase in total ionic conductance (Gt) in the presence of calcium ions (140% vs. 27%). However, the time constant for Gt to return to steady state was significantly longer in calcium-free solutions (122 vs. 18 min.). This study demonstrates that the biological effects of ultrasound are influenced by calcium ions. Furthermore, the recovery time constants confirm recent findings regarding the function of calcium ions in the formation of tight junctions. The role of free radicals produced by cavitation and calcium potentiated lipid and protein peroxidation is discussed.

Overt viral diseases induced from apparent latency following parasitization by the ichneumonid wasp, Hyposoter exiguae.

Latent and/or asymptomatic viral infections are commonplace in insects, but factors inducing overt disease are poorly understood. Here we show that in Trichoplusia ni larvae parasitized by the ichneumonid wasp, Hyposoter exiguae, overt, lethal disease may on occasion be observed; however, disease has been consistently absent in control (non-parasitized) larvae. Thus far, we have detected two such diseases, one of which is caused by a granulosis virus affecting primarily fat body tissue. The other is associated with the presence of two viruses replicating together in larval midgut epithelial cells; of these, one has been identified as a non-occluded form of TnCPV. Since H. exiguae carries a polydnavirus, which is delivered to host larvae during oviposition, it is tempting to speculate that viral latency may in some cases be broken through immunosuppressive activity resulting from insect parasitism.

Three related TrIV genes: comparative sequence analysis and expression in host larvae and Cf-124T cells.

We report on the cloning and sequencing of two Tranosema rostrale ichnovirus (TrIV) genes, and assess their relatedness to TrV1, the gene encoding the most abundant TrIV transcript in last-instar Choristoneura fumiferana larvae parasitized by T. rostrale. One of the two newly isolated genes, TrV2, features an organization similar to that of TrV1, with one intron flanked by two exons; it encodes a 102 amino acid protein showing 79% similarity to TrV1. The third gene, TrV4, encodes a larger protein (143 aa) displaying similarity to the other two only over the first approximately 50 amino acid residues of its sequence; the remaining portion contains an imperfect octad repeat. Although the TrV4 gene contains only one exon, it has an intron similar in size and sequence to that of TrV1 and TrV2; in fact, the non-coding regions of all three genes show higher sequence identity than the coding regions, pointing to their common origin. Southern analysis suggests that each gene maps to a different TrIV genome segment, with homologous sequences apparently present on other segments. TrV1 and TrV4 transcription in penultimate (5th) instar hosts, parasitized shortly after the molt, was strong for both genes 1 and 2 days p.p., with transcript abundance decreasing after the final molt; thus, neither of these genes is upregulated during induction of developmental arrest in last-instar hosts. Cf-124T cells inoculated with T. rostrale calyx fluid showed significant levels of apoptosis 24-72 h p.i.; TrV1 was detected in the culture medium, suggesting that this and/or other TrIV-encoded proteins may be responsible for the observed cytopathic effect. Southern and Northern analyses, using DNA and RNA extracted from infected Cf-124T cells, revealed the presence of both TrV1- and TrV4-carrying genome segments and transcripts, but neither DNA, at least in episomal form, nor mRNA persisted for more than a few days p.i. This in vitro system may provide a suitable starting point for the study of TrIV gene functions.

The ReactorSTM: atomically resolved scanning tunneling microscopy under high-pressure, high-temperature catalytic reaction conditions.

To enable atomic-scale observations of model catalysts under conditions approaching those used by the chemical industry, we have developed a second generation, high-pressure, high-temperature scanning tunneling microscope (STM): the ReactorSTM. It consists of a compact STM scanner, of which the tip extends into a 0.5 ml reactor flow-cell, that is housed in a ultra-high vacuum (UHV) system. The STM can be operated from UHV to 6 bars and from room temperature up to 600 K. A gas mixing and analysis system optimized for fast response times allows us to directly correlate the surface structure observed by STM with reactivity measurements from a mass spectrometer. The in situ STM experiments can be combined with ex situ UHV sample preparation and analysis techniques, including ion bombardment, thin film deposition, low-energy electron diffraction and x-ray photoelectron spectroscopy. The performance of the instrument is demonstrated by atomically resolved images of Au(111) and atom-row resolution on Pt(110), both under high-pressure and high-temperature conditions.