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Macrophages are one of the most important HIV-1 target cells. Unlike CD4+ T cells, macrophages are resistant to the cytophatic effect of HIV-1. They are able to produce and harbor the virus for long periods acting as a viral reservoir. Candida albicans (CA) is a commensal fungus that colonizes the portals of HIV-1 entry, such as the vagina and the rectum, and becomes an aggressive pathogen in AIDS patients. In this study, we analyzed the ability of CA to modulate the course of HIV-1 infection in human monocyte-derived macrophages. We found that CA abrogated HIV-1 replication in macrophages when it was evaluated 7 days after virus inoculation. A similar inhibitory effect was observed in monocyte-derived dendritic cells. The analysis of the mechanisms responsible for the inhibition of HIV-1 production in macrophages revealed that CA efficiently sequesters HIV-1 particles avoiding its infectivity. Moreover, by acting on macrophages themselves, CA diminishes their permissibility to HIV-1 infection by reducing the expression of CD4, enhancing the production of the CCR5-interacting chemokines CCL3/MIP-1α, CCL4/MIP-1β, and CCL5/RANTES, and stimulating the production of interferon-α and the restriction factors APOBEC3G, APOBEC3F, and tetherin. Interestingly, abrogation of HIV-1 replication was overcome when the infection of macrophages was evaluated 2-3 weeks after virus inoculation. However, this reactivation of HIV-1 infection could be silenced by CA when added periodically to HIV-1-challenged macrophages. The induction of a silent HIV-1 infection in acrophages at the periphery, where cells are continuously confronted with CA, might help HIV-1 to evade the immune response and to promote resistance to antiretroviral therapy. Fil: Rodríguez Rodrígues, Christian Fernando Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomedicas en Retrovirus y Sida; Argentina; Fil: Remes Lenicov, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomedicas en Retrovirus y Sida; Argentina; Fil: Jancic, Carolina Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biologia y Medicina Experimental (i); Argentina; Fil: Sabatte, Juan Atilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomedicas en Retrovirus y Sida; Argentina; Fil: Cabrini, Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomedicas en Retrovirus y Sida; Argentina; Fil: Ceballos, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomedicas en Retrovirus y Sida; Argentina; Fil: Merlotti, Antonela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomedicas en Retrovirus y Sida; Argentina; Fil: Gonzalez, Heidi Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomedicas en Retrovirus y Sida; Argentina; Fil: Ostrowski, Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomedicas en Retrovirus y Sida; Argentina; Fil: Geffner, Jorge Raul. Consejo Nacional de Investigaciones Científicas y Técnicas . Oficina de Coordinación Administrativa Houssay. Instituto de Inmunologia, Genetica y Metabolismo; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomedicas en Retrovirus y Sida; Argentina

HIV vaccines have not been able to provide immune protection against sexually-transmitted HIV. We hypothesized that semen has an active role in the transmission of HIV by influencing the early events of the immune response. This study analyzed the ability of spermatozoa and seminal plasma (SP) to modulate in vitro the differentiation profile of human monocytederived dendritic cells (DC). Methods

The C-type lectin receptor dendritic cell-specific ICAM-3–grabbing nonintegrin (DC-SIGN) is an important player in the recognition of pathogens by dendritic cells. A plethora of pathogens including viruses, bacteria, parasites, and fungi are recognized by DC-SIGN through both mannose and fucose-containing glycans expressed on the pathogen surface. In this study, we identified semen clusterin as a novel DC-SIGN ligand. Semen clusterin, but not serum clusterin, expresses an extreme abundance of fucose-containing blood-type Ags such as Lex and Ley, which are both excellent DC-SIGN ligands. These motifs enable semen clusterin to bind DC-SIGN with very high affinity (Kd 76 nM) and abrogate the binding of HIV-1 to DC-SIGN. Depletion of clusterin from semen samples, however, did not completely prevent the ability of semen to inhibit the capture of HIV-1 by DC-SIGN, supporting that besides clusterin, semen contains other DC-SIGN ligands. Further studies are needed to characterize these ligands and define their contribution to the DC-SIGN–blocking activity mediated by semen. Clusterin is an enigmatic protein involved in a variety of physiologic and pathologic processes including inflammation, atherosclerosis, and cancer. Our results uncover an unexpected heterogeneity in the glycosylation pattern of clusterin and suggest that the expression of high concentrations of fucose-containing glycans enables semen clusterin to display a unique set of biological functions that might affect the early course of sexually transmitted infectious diseases.

Background Genetic characterization of HIV-1 in Argentina has shown that BF recombinants predominate among heterosexuals and injecting drug users, while in men who have sex with men the most prevalent form is subtype B. Objectives The aim of this work was to investigate the presence of HIV dual infections in HIV-infected individuals with high probability of reinfection Study design Blood samples were collected from 23 HIV positive patients with the risk of reinfection from Buenos Aires. A fragment of the HIV gene pol was amplified and phylogenetic analyses were performed. Antiretroviral drug resistance patterns of all the sequences were analyzed. Results Five dual infections were detected with four patients coinfected with subtype B and BF recombinants and one patient was coinfected with two BF recombinants presenting different recombination patterns. Prolonged infection with a stable clinical condition was observed in the five individuals. Resistance mutation patterns were different between the predominant and the minority strains. Conclusions Our results show that HIV dual infection can occur with closely related subtypes, and even with different variants of the same recombinant form in certain populations. Clinical observations showed neither aggressive disease progression nor impact on the resistance patterns in the dually-infected patients.

Unprotected sexual intercourse between discordant couples is by far the most frequent mode of HIV-1 (human immunodeficiency virus type 1) transmission being semen the main vector for HIV-1 dissemination worldwide. Semen is usually considered merely as a vehicle for HIV-1 transmission. In this review we discuss recent observations suggesting that beyond being a carrier for virus particles semen markedly influences the early events involved in sexual transmission of HIV through the mucosal barriers. Fil: Sabatte, Juan Atilio. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Centro Nacional de Referencia del Sida; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina Fil: Remes Lenicov, Federico. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Centro Nacional de Referencia del Sida; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina Fil: Cabrini, Mercedes. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Centro Nacional de Referencia del Sida; Argentina Fil: Rodríguez Rodrígues, Christian Fernando Ariel. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Centro Nacional de Referencia del Sida; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina Fil: Ostrowski, Matias. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Centro Nacional de Referencia del Sida; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina Fil: Ceballos, Ana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Centro Nacional de Referencia del Sida; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina Fil: Amigorena, Sebastián. Inserm; Francia Fil: Geffner, Jorge Raul. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Centro Nacional de Referencia del Sida; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina

Previous studies have shown that histamine is able to modulate the function of dendritic cells (DCs). Histamine seems to be required for the normal differentiation of DCs. Moreover, it is capable of stimulating the chemotaxis of immature DCs and of promoting the differentiation of T CD4+ cells into a Th2 profile. In this study, we analyzed whether histamine was able to modulate endocytosis and cross-presentation mediated by immature DCs. Our results show that both functions are stimulated by histamine. Endocytosis of soluble HRP and FITC-OVA and cross-presentation of soluble OVA were markedly increased by histamine. Interestingly, stimulation of endocytosis and cross-presentation appeared to be mediated through different histamine receptors. In fact, the enhancement of endocytosis was prevented by the histamine2 receptor (H2R) antagonist cimetidine, whereas the stimulation of cross-presentation was prevented by the H3R/H4R antagonist thioperamide. Of note, contrasting with the observations made with soluble Ags, we found that histamine did not increase either the uptake of OVA-attached to latex beads, or the cross-presentation of OVA immobilized on latex beads. This suggests that the ability of histamine to increase endocytosis and cross-presentation is dependent on the Ag form and/or the mechanisms through which the Ag is internalized by DCs. Our results support that histamine may favor cross-presentation of soluble allergens by DCs enabling the activation of allergen-specific T CD8+ cells, which appears to play an important role in the development of allergic responses in the airway.

Compared with other lysophospholipid mediators such as sphingosine-1-phosphate and lysophosphatidic acid, little is known about the physiological significance of the related bioactive lysosphingolipid sphingosylphosphorylcholine (SPC), which is present in high-density lipoprotein particles. The present study was undertaken to evaluate the effect of SPC on human immature dendritic cells (DCs). Reverse transcription-polymerase chain reaction and flow cytometry assays revealed that DCs express two putative receptors for SPC, ovarian cancer G-protein-coupled receptor 1 and G-protein-coupled receptor 4. Exposure to SPC induced a rapid and transient increase in intracellular free calcium concentrations but did not stimulate endocytosis or chemotaxis of DCs. SPC increased the expression of HLA-DR, CD86 and CD83 and improved the T-cell priming ability of DCs, as well as the ability of DCs to stimulate the production of interferon-gamma by allogeneic peripheral blood mononuclear cells during the mixed lymphocyte reaction. Consistent with these results, we also observed that SPC stimulated the production of interleukin (IL)-12 and IL-18 by DCs. Taken together, our results support the notion that the accumulation of SPC in peripheral tissues during the course of inflammatory processes may favour the development of T helper type 1 immunity.

s / Placenta 36 (2015) 469e521 515 Objective: The aim of the study was to describe the placental microscopic features of the Southern elephant seal, Mirounga leonina. No descriptions of the placentae from the genusMirounga have been found in the available literature. Methods: Placentas from three elephant seals were collected after natural delivery at the Stranger Point rockery, close to the Argentinian Carlini Base scientific research station (South Shetland Islands, Antarctica), during the breeding period, the austral spring terrestrial phase in 2013. Samples were formalin-fixed and processed by histological routine techniques. Vimentin and cytokeratin filaments were immunohistochemically detected using a mouse monoclonal and a rabbit polyclonal antibody, respectively, and revealed with the EnVision® detection system+HRP. Results: As in other carnivores, the choriovitelin placenta of Mirounga leonina is zonary. The anular band showed multiple macroscopic orange areas, both in the margins and in the center of the labyrinth, which corresponded to hemosiderin aggregates located among trophoblast villi. Macroscopic hematomal areas were not observed. Based on chorionic villous arrangements, Mirounga placenta was labyrinthine, reminding the canine placenta. In the chorioallantoic membrane, numerous and remarkably thick fetal arterial vessels were observed. This pospartum placental labyrinth showed scarce and flattened trophoblast cells and was almost composed of maternal and fetal intermingled blood vessels. Fetal vessels were typically small, round and regular in shape whereas maternal vessels were larger and irregular, and exhibited attenuated endothelial cells (unlike those from domestic carnivores) and numerous leukocytes. Fetal vessels were between trophoblast cells resulting in a very thin placental barrier, otherwise endotheliochorial. We did not find vimentin positive cells (other than endothelial cells or circulating leukocytes) similar to decidual cells of the cat placenta. Conclusions: Based on this preliminary study we conclude that Mirounga leonina placenta shares some basic features with that of other carnivores but shows some peculiarities, especially related to the source of iron for the fetuses. PB.30. PROSTAGLANDIN E2 INHIBITS THE PROINFLAMMATORY PHENOTYPE INDUCED BY TGF-b ON MONOCYTE-DERIVED DENDRITIC CELLS Federico Remes Lenicov, Augusto Varese, Antonela Merlotti, Jorge Geffner, Ana Ceballos. Instituto de Investigaciones Biom edicas en Retrovirus y SIDA (UBA-CONICET), Buenos Aires, Argentina Objectives: The immunomodulatory properties of semen are well recognized, but details are lacking regarding its effect on dendritic cells, the immune cells in charge of deciding the type of response against foreign antigens. Previously, we have demonstrated that seminal plasma prostaglandins (PG) induce a tolerogenic profile on monocyte-derived dendritic cells (DCs). Human seminal plasma also contains high amounts of TGF-b, which has been shown to promote a proinflammatory phenotype in DCs. We aim to characterize the interaction between PG and TGF-b during the differentiation of DCs from monocytes. Methods: Seminal plasma was obtained by centrifugation of semen samples donated by healthy volunteers. DCs were obtained by incubating peripheral blood monocytes (>85% purity) with GM-CSF and IL-4 for 5 days, in the absence (control) or presence of TGF-b (TGF-DCs), PGE2 (PGDCs), the combination of these (TGF+PG-DCs) or seminal plasma (SP-DCs). DCs and their ability to expand the CD4+CD25+FoxP3+ lymphocyte population was analyzed by flow cytometry. Cytokine production was measured by ELISA in cell culture supernatants. Results: TGF-DCs showed a marked expression of CD1a and null expression of CD14. Addition of PGE2 (10-9 to 10-6 M) during differentiation of TGF-DCs reversed this phenotype, resulting in CD1a-CD14+ DCs, associated with tolerogenic properties and similar to that obtained for PG-DCs and SP-DCs. Moreover, stimulation of TGF-DCs with LPS resulted in increased production of IL-12p70 and IL-23 compared to control DCs, while TGF+PGDCs were unable to produce IL-12p70 or IL-23 upon stimulation, as observed also for PG-DCs and SP-DCs. Finally, in a mixed-lymphocyte reaction, TGF-DCs suppressed the expansion of CD4+CD25+FoxP3+ cells compared to control DCs. In contrast, we observed increased expansion of this population comparing control DCs with TGF+PG-DCs, PG-DCs and SPDCs. Conclusions: The presence of PGE2 during differentiation abolishes the proinflammatory properties elicited by TGF-b in monocyte-derived DCs. PB.31. POSSIBLE ROLE OF TRPV-1 AND AQPS IN THE REGULATION OF TROPHOBLAST CELL VOLUME Nora Martinez , Julieta Reppetti , Cyntia Ab an , Graciela Moya , Mariana Farina , Alicia E. Damiano . 1 Laboratorio de Fisiopatologia Placentaria, CEFyBO-CONICET, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina; 2 Laboratorio de Biologia de la Reproducci on, IFIBIO-CONICET, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina; 3 Fundaci on GENOS, Buenos Aires, Argentina Mammalian cells have homeostatic mechanisms that maintain body-fluid osmolality near 300 mOsm/kg through the intake or excretion of water and salts. This osmoregulation is vital to prevent changes in cell volume that result in irreversible damage. Transient receptor potential vanilloid type-1 (TRPV-1) is a cation channel that mediates Ca2+ influx in response to osmotic stress, acting as a hypertonicity sensor. Recently, we have described TRPV-1 in trophoblast cells. Aquaporins (AQPs) are a family of small integral membrane proteins that facilitate osmotically driven water transport. Although AQP1, AQP3 and AQP9 are highly expressed in trophoblasts during early gestation, their role is still unknown. Objective: To evaluate the contribution of AQPs and TRPV-1 in cell volume regulation of first trimester trophoblast and the consequences on cell viability. Methods: TRPV-1, AQP3 and AQP9 protein expressions were analyzed by Western blot and immunohistochemistry in first trimester human chorionic villous samples (CVS) and in the Swan-71 cell line. The effect of hyperosmolarity on each protein expression was evaluated in Swan-71 cells before and after the inhibition of AQPs with HgCl2. Cell viability was analyzed by MTT assay and cleaved caspase-3 expression. Results: TRPV-1, AQP3 and AQP9 expression was found in CVS and Swan71 cells. After exposure to hyperosmolarity, we observed that the expression of the three proteins increased (p

We describe the genetic diversity of currently transmitted strains of HIV-1 in men who have sex with men (MSM) in Buenos Aires, Argentina between 2000 and 2004. Nearly full-length sequence analysis of 10 samples showed that 6 were subtype B, 3 were BF recombinant and 1 was a triple recombinant of subtypes B, C and F. The 3 BF recombinants were 3 different unique recombinant forms. Full genome analysis of one strain that was subtype F when sequenced in pol was found to be a triple recombinant. Gag and pol were predominantly subtype F, while gp120 was subtype B; there were regions of subtype C interspersed throughout. The young man infected with this strain reported multiple sexual partners and sero-converted between May and November of 2004. This study reported for the first time the full genome analysis of a triple recombinant between subtypes B, C and F, that combines in one virus the three most common subtypes in South America.

Active surveillance of ambulatory and hospitalized children 2-23 months old in Cordoba, Argentina for invasive pneumococcal disease and radiographically confirmed "obvious" pneumonia revealed annual incidences of 206.8 and 2422 cases, respectively, per 100,000 children. The invasive pneumococcal disease incidence was substantially higher than those previously reported from Latin America and Europe.

To investigate GB virus C (GBV-C)/hepatitis G virus (HGV) mother-to-infant transmission when only 5′ noncoding region (NCR) sequences were available, a retrospective study was carried out. Although the 5′ NCR is widely used for GBV-C/HGV detection due to the high degree of sequence conservation among isolates (8), this fact clearly limits its potential use to trace chains of transmission, despite the presence of scattered subregions with higher heterogeneity. Nevertheless, since the 5′ NCR has been reported to be unmodified after 8.4 years of evolution (5), a mother-to-infant chain was expected to show (almost) identical sequences unless specific 5′ NCR variants were involved in selective transmission. Analyzed sequences were obtained from (i) a study group which encompassed plasma samples simultaneously obtained from 34 human immunodeficiency virus (HIV)-infected mothers (13 intravenous-drug users [IVDU] and 21 nonaddict women putatively infected by a heterosexual route [IHSR]) as well as from their respective infants (1 to 7 months old, without history of blood transfusion) born to either HIV-positive and GBV-C/HGV-infected mothers (n = 8) or to HIV-positive but GBV-C/HGV nonviremic mothers (n = 26) and (ii) a control group which comprised 31 5′ NCR sequences derived from contemporary isolates circulating in the city of Buenos Aires and 6 others from the rest of the world. Several precautions (3) as well as appropriate controls were included to minimize the possibility that sequence identity among samples was the mere result of PCR contamination: (i) samples from mothers and infants were analyzed separately (elapsed time, 2 months); (ii) each positive result was confirmed in duplicate; and (iii) one negative control (SDW) was included for every three samples. To estimate the potential influence of Taq-dependent misincorporated nucleotides during PCR amplification (4), three cDNAs from local isolates of GBV-C/HGV whose sequences (325 bp) had been previously established (6) were amplified in duplicate and bidirectionally sequenced. A total of 4 of 13 IVDU and 4 of 21 IHSR mothers (30.8 and 19.0%, respectively; P not significant) proved positive for GBV-C/HGV RNA ascribed to genogroup 2a (n = 4), 2b (n = 2), or 3 (n = 2). Only three of eight infants born from viremic mothers (and none from 26 nonviremic mothers) exhibited GBV-C/HGV RNA (37.5%; one born to an IVDU and two to IHSR GBV-C/HGV-positive mothers); their genogroups, as established by both restriction fragment length polymorphism and cDNA sequencing (8), were the same as those of their respective mothers. The phylogenetic analysis was based on both genetic distance (neighbor joining) (Fig. ​(Fig.1)1) and maximum parsimony (data available upon request) methodologies. Both procedures showed unambiguously a genetic relatedness (i.e., no mutation between them) in each GBV-C/HGV mother-infant pair. In contrast to such a lack of nucleotide differences among the three mother-infant pairs, a mean ± standard deviation of 11.56 ± 6.17 nucleotide (nt) replacements was found among unrelated chosen sequences (n = 155 pairs of sequences analyzed). These control sequences corresponded to simultaneously circulating strains in the city of Buenos Aires which were ascribed to the same genogroups putatively associated with transmission chains in this study (i.e., genogroups 2a [n = 17 isolates] and 3 [n = 9]). None of these 26 sequences were identical. When nucleotide replacements were analyzed separately among all included (sub)group 2a (n = 119) and group 3 (n = 36) pairs of sequences, means ± standard deviations of 10.13 ± 3.16 and 16.77 ± 9.77 changes, respectively, were recorded (P < 0.00001; Student t test [two-sided test]). However, one pair of epidemiologically unrelated sequences (Arg15/Arg25) exhibited only one nucleotide difference (a 1-nt gap), seemingly appearing genetically related by the neighbor-joining analysis (Fig. ​(Fig.1).1). When maximum parsimony was carried out, only the three pairs of mother-infant 5′ NCR sequences remained undoubtedly related, since the lengths of their respective tree segments (in units of expected nucleotide substitutions per site) were equal to 0 and those between the above-mentioned sequences exhibiting a 1-nt gap were equal to 0.1073. Such a discrepancy between the two phylogenetic methodologies might be attributable to the reported (7) known loss of information with neighbor joining compared with maximum parsimony (distance versus discrete methods, respectively). FIG. 1. Phylogenetic analysis of GBV-C/HGV sequences (nt positions 132 to 337) from mother A (MA) and infant A (IA), MB and IB, and MC and IC compared with those obtained from simultaneously circulating strains in Argentina (ARG) and the rest of the world (W). ... The use of one mutation as a cutoff to discriminate related versus unrelated 5′ NCR sequences has the inherent risk of being Taq dependent. However, sequencing of the three control cDNAs (2,150 nt) rendered uniformly conserved (and repeatedly obtained) results. Thus, considering one mutation as the best cutoff value to discriminate between the related and unrelated 5′ NCR sequences analyzed in this study, the Youden's Index (sensitivity + specificity − 1) was equal to 1, the maximum possible value (1). In agreement with this view, the probability that three pairs of 5′ NCR sequences were identical (between members of pairs) due to random events is less than 1/17,576 (1/26 × 1/26 × 1/26), or 0.000056895, since none of the 26 simultaneously circulating local isolates ascribed to the same genomic group or subgroup implicated in putative chains of transmission were identical. Such mathematical support is coincident with the epidemiological data, since the studied babies lacked any risk factor for GBV-C/HGV infection except the corresponding mother's ongoing infection. As a whole, results obtained provided strong support to suggest the occurrence of GBV-C/HGV mother-to-infant transmission. The 5′ NCR was recently studied in transmission chains among hemodialyzed patients (2). To our knowledge, this is the first report to use both mathematical and phylogeneticanalyses to examine the eventual use of 5′ NCR sequences—when they are the only available data—to evaluate putative transmission chains.

Oxytocin and prostaglandins (PGs) are hormones involved in labor and are used clinically for its induction. In this study the effect of oxytocin, PGF(2alpha), and PGE(2) on Humour immunodeficiency virus-1 production in acutely and persistently infected cells was measured. No significant effect on p24 antigen production was found with oxytocin or PGs, except for a transient decrease in persistently infected cells treated with 1 micro M PGF(2alpha). These results showed that oxytocin and PGs could be used clinically for labor induction without any direct enhancement in viral production. Besides, the results with PGF(2alpha) at the highest concentration studied may indicate a pharmacological effect.

Detection of anti-HIV-1 IgA antibodies using a modified ELISA test for the early diagnosis of perinatally acquired HIV-1 infection in children treated with protocol ACTG 076 was evaluated. A total of 177 sera were obtained from 141 infants between 1 and 12 months of age (46 were treated and 95 were non-treated with protocol ACTG 076) and tested for HIV IgA antibodies by an ELISA test after removal of IgG with recombinant protein G. Infants were classified according to CDC's classification system after a follow-up until 20 months of age. Of the 46 treated children 22 turned out to be infected and in the group of 95 untreated children, 52 were infected. All 81 samples from uninfected children treated or untreated with protocol ACTG 076 were persistently IgA-negative. HIV IgA antibodies were detected in 14 of 25 plasma samples from infected children with treatment, and in 58 of 71 samples in infected children without treatment. Considering that the sensitivity of this test is lower in children younger than 6 months the population of children studied was divided into two groups; those under and those over 6 months of age. No significant differences were observed in the detection of IgA in treated or untreated children in both age groups. The overall specificity of the test was 100 per cent; sensitivity in children older than 6 months was 76.92 per cent in treated children and 93.10 per cent in untreated children. In spite of the small number of samples studied it could be demonstrated that treatment with zidovudine does not affect the detection of IgA antibodies. This is a simple and inexpensive method that could be used for diagnosis of treated and untreated children in developing countries.

The 1991 Peruvian cholera epidemic has thus far been responsible for 600,000 cholera cases in Peru. In an attempt to design a cholera surveillance program in the capital city of Lima, weekly sewage samples were collected between August 1993 and May 1996 and examined for the presence of Vibrio cholerae O1 bacteria and V. cholerae O1 bacteriophages (i.e., vibriophages). During the 144 weeks of surveillance, 6,323 cases of clinically defined cholera were recorded in Lima. We arbitrarily defined an outbreak as five or more reported cases of cholera in a week. The odds of having an outbreak were 7.6 times greater when V. cholerae O1 was present in sewage water during the four previous weeks compared with when it was not (P < 0.001). Furthermore, the odds of having an outbreak increased as the number of V. cholerae O1 isolations during the previous 4 weeks increased (P < 0.001). The odds of having an outbreak were 2.4 times greater when vibriophages were present in sewage water during the four previous weeks compared with when they were not, but this increase was not statistically significant (P = 0.15). The odds of having an outbreak increased as the number of vibriophage isolations during the previous 4 weeks increased (P < 0.05). The signaling of a potential cholera outbreak 1 month in advance may be a valuable tool for implementation of preventive measures. In Peru, active surveillance for V. cholerae O1 and possibly vibriophages in sewage water appears to be a feasible and effective means of predicting and outbreak of cholera.

Although the development of an acidic tissue environment or acidosis is a hallmark of inflammatory processes, few studies analyze the effect of extracellular pH on immune cells. We have previously shown that exposure of murine dendritic cells (DCs) to pH 6.5 stimulates macropinocytosis and cross-presentation of extracellular Ags by MHC class I molecules. We report that the transient exposure of human DCs to pH 6.5 markedly increases the expression of HLA-DR, CD40, CD80, CD86, CD83, and CCR7 and improves the T cell priming ability of DCs. Incubation of DCs at pH 6.5 results in the activation of the PI3K/Akt and the MAPK pathways. Using specific inhibitors, we show that the maturation of DCs induced by acidosis was strictly dependent on the activation of p38 MAPK. DC exposure to pH 6.5 also induces a dramatic increase in their production of IL-12, stimulating the synthesis of IFN-γ, but not IL-4, by Ag-specific CD4+ T cells. Interestingly, we find that suboptimal doses of LPS abrogated the ability of pH 6.5 to induce DC maturation, suggesting a cross-talk between the activation pathways triggered by LPS and extracellular protons in DCs. We conclude that extracellular acidosis in peripheral tissues may contribute to the initiation of adaptive immune responses by DCs, favoring the development of Th1 immunity.

Address: 1National Reference center for AIDS, Buenos Aires, Argentina, 2Institut Curie, Paris, France, 3Institut de Biologie Structurale, UMR CNRSCEA-UJF, Grenoble, France, 4Institut de Biologie Structurale, UMR CNRS-CEA-UJF, Grenoble, France, 5UMR CNRS 8576, Unite de Glycobiologie Structurale et fonctionnelle, Lille, France, 6Unite d'Immunologie Virale, Institut Pasteur, Paris, France and 7U932 INSERM, Institut Curie, Immunite et Cancer, Paris, France * Corresponding author

MIAMI (AP) ” Pedro Escalona endured a grueling journey from Venezuela to Texas, made a brief stopover at a San Antonio migrant center, crossed paths with an operative of Florida Gov. Ron DeSantis ” one who promised a free charter flight to Delaware ” then learned the flight had been scuttled and caught a plane to New York City, where he ended up in a homeless shelter.And now, days later, he sat forlornly on a bench in Doral, Florida, outside a Best Western, contemplating life™s odd twists. The company he had been working for had fired him, kicking him and three others out of the hotel room they had been staying in for a week. He had spent the night before on the grass of the hotel under a palm tree. [ABSTRACT FROM PUBLISHER]