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P Ave

Publications and source records attributed to P Ave.

11 recordsLinked to original sources

Persistent infection of B lymphocytes by bovine respiratory syncytial virus.

Bovine respiratory syncytial virus (BRSV) is a major cause of respiratory disease in young cattle. Here we demonstrate BRSV persistence at low levels in tracheobronchial and mediastinal lymph nodes up to 71 days after the experimental infection of calves. Positive results were obtained on viral genomic RNA and messenger RNA coding for the nucleoprotein, glycoprotein (G), and fusion protein (F). G and F proteins were also detected in the pulmonary lymph nodes by immunohistochemistry. Double-staining experiments revealed that viral antigen was present in B-lymphocytes. Coculture experiments with the lymph node cells showed that the virus was still able to infect permissive target cells, even though no cytopathic effect was recorded. In vitro studies indicate that BRSV was still able to replicate in bovine B-lymphocyte cell lines 6 months after infection. These results may also be relevant to the understanding not only of the epidemiology and the peculiarities of the immune response of BRSV infections but also of human respiratory syncytial virus infections.

Animals↗

Blockade of CD14 aggravates experimental shigellosis.

Shigella infections lead to severe inflammation associated with destruction of colonic mucosa. We assessed the effect of in vivo blockade of CD14 on the outcome of experimental Shigella infection in rabbits. A total of 17 rabbits were divided into two groups: 8 received a single i.v. dose of anti-rabbit CD14 monoclonal antibody prior to infection with an invasive Shigella flexneri strain; the remainder served as controls. The anti-CD14-treated rabbits exhibited more severe tissue destruction and a 50-fold increase in bacterial invasion of the intestinal mucosa when compared to controls. Similar numbers of polymorphonuclear leukocytes were recruited to the intestinal mucosa in both groups despite the massive bacterial invasion seen in the CD14-blocked group. No statistically significant differences were seen in levels of IL-1beta nor in the ratio of IL-1RA/IL-1beta for either group. In contrast, higher quantities of TNF-alpha were observed in the CD14-blocked group. To conclude, anti-CD14 treatment had a detrimental effect on the capacity of Shigella-infected animals to clear the infection.

Animals↗

Blockade of CD14 increases Shigella-mediated invasion and tissue destruction.

Shigella is a diarrheal pathogen that causes disease through invasion of the large intestinal mucosa. The endotoxin of the invading bacterium may play a key role in the disease process by causing inflammation and tissue injury during infection. Earlier studies have shown that various animal species lacking functional CD14 were protected against endotoxin-mediated shock. Rabbits experimentally infected with Shigella were used to test the hypothesis that blockade of endotoxin-induced cell activation with anti-CD14 mAb would diminish inflammation and thus disease severity. Unexpectedly, we observed that the intestinal mucosa of anti-CD14-treated animals exhibited a 50-fold increase in bacterial invasion and more severe tissue injury compared with controls. Despite higher bacterial loads in treated animals, the numbers of polymorphonuclear leukocytes that were recruited to the infection site were similar to those in controls. Furthermore, the phagocytic cells of CD14-blocked animals produced IL-1 and TNF-alpha. Moreover, in vitro blockade of CD14 did not impede bactericidal activity. Thus, anti-CD14 treatment interfered with host defense mechanisms involved with removal/eradication of Shigella.

Animals↗

High levels of viral replication during primary simian immunodeficiency virus SIVagm infection are rapidly and strongly controlled in African green monkeys.

In contrast to pathogenic human immunodeficiency virus and simian immunodeficiency virus (SIV) infections, chronic SIVagm infections in African green monkeys (AGMs) are characterized by persistently low peripheral and tissue viral loads that correlate with the lack of disease observed in these animals. We report here data on the dynamics of acute SIVagm infection in AGMs that exhibit remarkable similarities with viral replication patterns observed in peripheral blood during the first 2 weeks of pathogenic SIVmac infections. Plasma viremia was evident at day 3 postinfection (p.i.) in AGMs, and rapid viral replication led by days 7 to 10 to peak viremias characterized by high levels of antigenemia (1.2 to 5 ng of p27/ml of plasma), peripheral DNA viral load (10(4) to 10(5) DNA copies/10(6) peripheral blood mononuclear cells [PBMC]), and plasma RNA viral load (2 x 10(6) to 2 x 10(8) RNA copies/ml). The lymph node (LN) RNA and DNA viral load patterns were similar to those in blood, with peaks observed between day 7 and day 14. These values in LNs (ranging from 3 x 10(5) to 3 x 10(6) RNA copies/10(6) LN cell [LNC] and 10(3) to 10(4) DNA copies/10(6) LNC) were at no time point higher than those observed in the blood. Both in LNs and in blood, rapid and significant decreases were observed in all infected animals after this peak of viral replication. Within 3 to 4 weeks p. i., antigenemia was no longer detectable and peripheral viral loads decreased to values similar to those characteristic of the chronic phase of infection (10(2) to 10(3) DNA copies/10(6) PBMC and 2 x 10(3) to 2 x 10(5) RNA copies/ml of plasma). In LNs, viral loads declined to 5 x 10(1) to 10(3) DNA copies and 10(4) to 3 x 10(5) RNA copies per 10(6) LNC at day 28 p.i. and continued to decrease until day 84 p.i. (<10 to 3 x 10(4) RNA copies/10(6) LNC). Despite extensive viremia during primary infection, neither follicular hyperplasia nor CD8(+) cell infiltration into LN germinal centers was detected. Altogether, these results indicate that the nonpathogenic outcome of SIVagm infection in its natural host is associated with a rapidly induced control of viral replication in response to SIVagm infection, rather than with a poorly replicating virus or a constitutive host genetic resistance to virus replication.

Animals↗

Abnormal organisation of the splenic marginal zone and the correlated leukocytosis in lymphotoxin-alpha and tumor necrosis factor alpha double deficient mice.

In this study we further characterized the phenotype at the homeostasis of mice genetically deficient in Tumor Necrosis Factor-alpha and Lymphotoxin-alpha (LT-alpha TNF-alpha -/-). As initially observed in LT-alpha -/- mice, these mice are devoid of lymph nodes and Peyer's patches, while in their spleen the white and red pulp domains are no more detectable. In the blood the leukocytosis dominated by lymphocytosis is not solely due to the absence of lymph nodes. Indeed, this abnormality was shown to be correctable by the transfer of wild type bone marrow in the absence of lymph node. We now report that the metallophilic macrophages of the marginal zone are no more detectable with an antibody reactive to sialoadhesin, a macrophage restricted transmembrane molecule known to bind myeloid and lymphoid cells. The absence of sialoadhesin within the marginal zone, a critical domain for lymphocyte trafficking towards the white pulp suggests a possible cellular basis for the observed blood leukocytosis. In addition, in the peritoneal cavity of LT-alpha TNF-alpha-/- mice, the size of the resident leukocyte population is increased. By their amplitudes these leukocytosis are similar within the blood and the peritoneal compartments.

Animals↗

Virulence of alkaline protease-deficient mutants of Aspergillus fumigatus.

The gene encoding the secreted alkaline protease, a suspected virulence factor of Aspergillus fumigatus, was inactivated by gene disruption. The disruption was performed by transformation of a pathogenic strain of the fungus with a linear DNA fragment carrying the gene from which the central part was replaced by the selectable Escherichia coli hygromycin B dominant resistance marker. Two transformants were shown to produce no alkaline protease. Restriction fragment analysis of the DNA of these two transformants was consistent for chromosomal integration of the disrupted gene by homologous recombination. Both isogenic alkaline protease-producing and non-producing A. fumigatus strains invaded lung tissues, causing comparable mortality in immunosuppressed mice. A significant residual proteolytic activity observed in alkaline protease non-producing strain cultures could play a role in the invasion of the tissues by the fungus.

Animals↗

[Human protothecosis and environment].

Protothecosis are uncommon infections caused by Prototheca, considered to be achlorophylous algae. Nearly 80 human cases are reported in the literature since the first case described by Davies and Wakelin in 1964 in Sierra Leone (11). The disease have been identified in Europe, Asia (Japan, Thailand, China), Oceania and in the United States with 40 cases, particularly in the Southeast. Clinically, three clinical manifestations can be observed: 1) cutaneous lesions: papules, plaques or eczematoid, papulo-nodular areas of the extremities, 2) olecranon bursitis which occurred in 25% of cases, 3) systemic protothecosis. An immunosuppressive factor local or general can be found in half of the cases and the first description of algal meningitis was reported in a patient with AIDS in association with Cryptococcus neoformans. Because the disease is clinically not suspected, the diagnosis is often provided by histology showing a dermic granuloma with endospores. The characteristic feature of protothecosis in tissues is the presence of specific mature sporangia of Prototheca wickerhamii with the pattern of morula. The organism was PAS, Grocott and mucicarmin positive. The ecology was studied by Clark (7), Pidoux (23), Pore (25) and Sudman (27). Prototheca are ubiquitous inhabitants of sewages and are found in slime flux and animal wastes contaminating different aquatic systems. The transmission generally occurred by traumatic inoculation. Prototheca are also found in the digestive system of man and animals without never invasion of the epithelium and mucosae in experimental models. The pathogenicity and virulence are moderate and they are considered as rare opportunistic agents.

Animals↗

[5 new cases of entomophthoromycosis observed in Cameroon. Role of immunofluorescence in thr diagnosis].

The authors present five new cases of entomophthoromycosis observed during three years of histopathology in Cameroon. Three classic cases of rhinoentomophthoromycosis. In one case, Conidiobolus coronatus was isolated. Two cases of subcutaneous entomophthoromycosis, without isolation of the germ. In one observation, the clinical and histological aspect suggested mucormycosis post entomophthoromycosis. An immunofluorescence technique showed the Basidiobolus haptosporus to be the real cause.

Adult↗

[Role of delta viruses in fulminating hepatitis in Central Africa].

The delta virus (DV) was shown to be the predominant but not exclusive aetiology in 124 cases of fulminating hepatitis (FH) in the Central African Republic. The condition occurs in an endemo-epidemic form in young adults with no apparent risk factors. The mortality is high (88 p. 100) and the clinical features well established. After a short prodromic period, the patients develop severe jaundice, hepatic encephalopathy, and, in over 1/3 of cases, severe haemorrhage. Biologically, the main changes are related to hepatic cytolysis and insufficiency. Histology shows appearances of spongiocytic (steatosic) hepatitis in 81 p. 100 of cases. HBS antigen is found in 90 p. 100 of cases and DV markers are present in 53 p. 100 of these. The HBS Ag also occurs in 60 to 90 p. 100 of the close relatives of the patients and anti-DV antibodies occur in 40 to 90 p. 100 of these subjects. To the authors' knowledge, this is the first published series to demonstrate FH associated with DV in the African continent.

Adolescent↗

Evaluation of the placental environment with a new in vitro model of histocultures of early and term placentae: determination of cytokine and chemokine expression profiles.

We aimed to set up and validate a new in vitro model of placental histocultures, for the evaluation of cytokine and chemokine profiles of the placental environment, over a long culture period. Micro-explant cultures from 6 early and 6 term placentae were set up on collagen sponge gel supports at a liquid/air interface. At various times during culture, we analyzed tissue morphology and cell death by microscopy and quantified beta-hCG production and mRNA levels for beta-hCG and insulin-like 4 (INSL4). Levels of IL-6, LIF, TNF alpha, IL-10, IFN-gamma, IL-16 and RANTES in the medium were measured by ELISA on days 1, 4 and 7 of culture. SDF-1 mRNA expression was determined by real-time PCR at the same time points. Histocultures from early and term placentae remained viable until day 10. High levels of IL-6 and LIF production, low levels of TNF alpha, IL-10 and IFN-gamma production and significant SDF-1 expression were observed. These data indicate that placental histoculture is a suitable and reliable in vitro model for studying the placental environment.

Adult↗

Antigenic variation of Borrelia turicatae Vsp surface lipoproteins occurs in vitro and generates novel serotypes.

As a means of avoiding the host immune response, the tick-borne relapsing fever spirochete Borrelia turicatae undergoes antigenic variation in its abundant surface lipoproteins. In this study, B. turicatae strain Oz1, serotype B, was subcultured in vitro and cloned by limited dilutions after 50 passages. Four different serotypes (serotypes A, B, E, and F) differing by their expressed Vsp lipoproteins were isolated. Using pulsed-field gel electrophoresis, we showed that the variability in surface-exposed proteins is correlated with rearrangement between different linear plasmids, defining serotype-specific plasmid profiles. Moreover, we determined the nucleotide sequence of genes encoding the VspE and VspF lipoproteins, corresponding to the two novel serotypes E and F, respectively. Our results showed that antigenic variation in B. turicatae occurs spontaneously in vitro, in the absence of immune selection.

Antigenic Variation↗