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61.
Sandra F. Moreira-Silva Eliana Zandonade Diana O. Frauches Elisa A. Machado Lays Ignacia A. Lopes Lívia L. Duque Polyana P. Querido Angélica E. Miranda 《PloS one》2013,8(12)
Background
Studying diseases associated with AIDS is essential for establishing intervention strategies because comorbidities can lead to death. The objectives were to describe the frequency of comorbidities and verify their distribution according to demographic, epidemiological and clinical data as well as to classify diseases in children and adolescents with AIDS in Vitória, Brazil.Methods
A retrospective cohort study was conducted among children with AIDS, as defined according to the criteria established by the Ministry of Health, who acquired HIV via vertical transmission, were aged 0 to 18 years, and were monitored at a referral hospital from January 2001 to December 2011.Results
A total of 177 patients were included, of whom 97 were female (55%). There were 60 patients (34%) <1 year old, 67 patients (38%) between the ages of 1 and 5, and 50 patients (28%) ≥6 years of age included at the time of admission to the Infectious Diseases Ward. Regarding clinical-immunological classification, 146 patients (82.5%) showed moderate/severe forms of the disease at the time of admission into the Ward, and 26 patients (14.7%) died during the study. The most common clinical signs were hepatomegaly (81.62%), splenomegaly (63.8%), lymphadenopathy (68.4%) and persistent fever (32.8%). The most common comorbidities were anaemia (67.2%), pneumonia/septicaemia/acute bacterial meningitis (ABM) (64.2%), acute otitis media (AOM)/recurrent sinusitis (55.4%), recurrent severe bacterial infections (47.4%) and dermatitis (43.1%). An association between severe clinical-immunological classification and admission to the Ward for children aged less than one year old was found for several comorbidities (p<0.001).Conclusion
Delayed diagnosis was observed because the majority of patients were admitted to the Infectious Diseases Ward at ≥1 year of age and were already presenting with serious diseases. The general paediatrician should be alert to this possibility to make an early diagnosis in children infected with HIV. 相似文献62.
63.
CD46 is a cellular receptor for human herpesvirus 6 总被引:29,自引:0,他引:29
Human herpesvirus 6 (HHV-6) is the etiologic agent of exanthema subitum, causes opportunistic infections in immunocompromised patients, and has been implicated in multiple sclerosis and in the progression of AIDS. Here, we show that the two major HHV-6 subgroups (A and B) use human CD46 as a cellular receptor. Downregulation of surface CD46 was documented during the course of HHV-6 infection. Both acute infection and cell fusion mediated by HHV-6 were specifically inhibited by a monoclonal antibody to CD46; fusion was also blocked by soluble CD46. Nonhuman cells that were resistant to HHV-6 fusion and entry became susceptible upon expression of recombinant human CD46. The use of a ubiquitous immunoregulatory receptor opens novel perspectives for understanding the tropism and pathogenicity of HHV-6. 相似文献
64.
Defective dendritic cell migration and activation of adaptive immunity in PI3Kgamma-deficient mice 总被引:6,自引:0,他引:6
Del Prete A Vermi W Dander E Otero K Barberis L Luini W Bernasconi S Sironi M Santoro A Garlanda C Facchetti F Wymann MP Vecchi A Hirsch E Mantovani A Sozzani S 《The EMBO journal》2004,23(17):3505-3515
Gene-targeted mice were used to evaluate the role of the gamma isoform of phosphoinositide 3-kinase (PI3Kgamma) in dendritic cell (DC) migration and induction of specific T-cell-mediated immune responses. DC obtained from PI3Kgamma-/- mice showed a reduced ability to respond to chemokines in vitro and ex vivo and to travel to draining lymph nodes under inflammatory conditions. PI3Kgamma-/- mice had a selective defect in the number of skin Langerhans cells and in lymph node CD8alpha- DC. Furthermore, PI3Kgamma-/- mice showed a defective capacity to mount contact hypersensitivity and delayed-type hypersensitivity reactions. This defect was directly related to the reduced ability of antigen-loaded DC to migrate from the periphery to draining lymph nodes. Thus, PI3Kgamma plays a nonredundant role in DC trafficking and in the activation of specific immunity. Therefore, PI3Kgamma may be considered a new target to control exaggerated immune reactions. 相似文献
65.
Pinto MR de Sá AC Limongi CL Rozental S Santos AL Barreto-Bergter E 《Microbes and infection / Institut Pasteur》2004,6(14):1259-1267
Pseudallescheria boydii is an emerging fungal pathogen that has a worldwide distribution. Virulence mechanisms of P. boydii are largely unknown. We studied the interaction between P. boydii and HEp2 cells and demonstrated that conidia of P. boydii attached to, and were ingested by, HEp2 cells in a time-dependent process. After 2 h of interaction, the conidia produced a germ-tube like projection, which was able to penetrate the epithelial cell membrane. Recently, our group characterized a peptidorhamnomannan (PRM) antigen on the cell surface of P. boydii. In order to better understand the role played by this surface glycoconjugate during cell adhesion and endocytosis, inhibition assays were performed using intact PRM and anti-PRM polyclonal antibody. When HEp2 cells were pre-treated with whole PRM molecule, the adhesion and endocytic indices were, respectively, 50% and 60% lower than in non-treated epithelial cells. Moreover, when the conidial cells were pre-incubated with anti-PRM antibodies, the adherence and endocytosis processes were inhibited in a dose-dependent manner. As PRM influenced the conidia P. boydii-HEp2 cell interaction, we also performed inhibition assays in order to observe which PRM moieties could be involved in this process. Treatment of PRM with proteinase K promoted a slight inhibition of adhesion. However, the de-O-glycosylated PRM molecule as well as the monosaccharide mannose was able to efficiently inhibit the adhesion and endocytic processes. In addition, our results indicate for the first time that P. boydii PRM binds to a polypeptide of 25 kDa on the HEp2 cell surface. 相似文献
66.
Carlos A Aguilar-Salinas Andréia Assis-Luores-Vale Benjamín Stockins Hector Mario Rengifo Dondici José Filho Abrahão Afiune Neto Marcílio Lísia Rabelo Kerginaldo Paulo Torres Egídio Paulo de José Oliveira Carlos Alberto Machado Eliana Reyes Victor Saavedra Fernando Florenzano Ma Victoria Hernández Hernandez Sergio Jiménez Erika Ramírez Cuauhtémoc Vazquez Saul Salinas Ismael Hernández Octavio Medel Ricardo Moreno Paula Lugo Ricardo Alvarado Roopa Mehta Victor Gutierrez Francisco J Gómez Pérez 《Cardiovascular diabetology》2004,3(1):1-6
Background
Microalbuminuria and subsequent progression to proteinuria and nephropathy is associated with increased oxidative stress, increased inflammatory cytokines and increased cardiovascular (CVD) risk. The common functional IL-6 -174G>C gene variant is also associated with elevated levels of inflammatory cytokines and CVD risk.Methods
The aim of this study was to examine the association between the IL-6 -174G>C gene variant with plasma total antioxidant status (TAOS) in 552 subjects with type 2 diabetes in relation to urinary protein excretion.Results
In subjects free from CVD, there was a significant interaction between urinary protein excretion (normoalbuminuria/ microalbuminuria/proteinuria) and the -174C allele (compared to -174GG) in determining plasma TAOS (p value for interaction = 0.03). In the -174C allele carriers there was a significant association between plasma TAOS and urinary protein excretion: normalbuminuria v microalbuminuria v proteinuria: 44.30% ± 11.32 vs. 39.74% ± 14.83 vs. 37.93% ± 16.42, ANOVA p = 0.025. In those with CVD, no interaction or association was observed with the -174C allele (p = 0.246).Conclusion
The IL-6 -174G>C gene variant is associated with differences in plasma oxidative stress in response to altered protein excretion in subjects with type 2 diabetes. 相似文献67.
De Sousa MO Santoro MM De Souza Figueiredo AF 《Journal of enzyme inhibition and medicinal chemistry》2004,19(4):317-325
Hydrolysis of D-valyl-L-leucyl-L-arginine p-nitroanilide by human tissue kallikrein (hK1) was studied in the absence and in the presence of increasing concentrations of the following chloride salts: sodium, potassium, calcium, magnesium and aluminium. The data indicate that the inhibition of hK1 by sodium, potassium, calcium and magnesium is linear competitive and that divalent cations are more potent inhibitors of hK1 than univalent cations. However the inhibition of hK1 by aluminium cation is linear mixed, with the cation being able to bind to both the free enzyme and the ES complex. This cation was the best hK1 inhibitor. Aluminium is not a physiological cation, but is a known neurotoxicant for animals and humans. The neurotoxic actions of aluminium may relate to neuro-degenerative diseases. 相似文献
68.
Gantt KR Schultz-Cherry S Rodriguez N Jeronimo SM Nascimento ET Goldman TL Recker TJ Miller MA Wilson ME 《Journal of immunology (Baltimore, Md. : 1950)》2003,170(5):2613-2620
TGF-beta is a potent regulatory cytokine that suppresses expression of inducible NO synthase and IFN-gamma, and suppresses Th1 and Th2 cell development. We examined whether functionally active TGF-beta is present in the local environment surrounding the invading protozoan Leishmania chagasi. Our prior data showed that TGF-beta levels are significantly increased in L. chagasi-infected mice. In the current study, we found TGF-beta was also abundant in bone marrows of humans with acute visceral leishmaniasis but not in those of uninfected controls. Furthermore, L. chagasi infection caused an increase in biologically active TGF-beta in human macrophage cultures without changing the total TGF-beta. Therefore, we investigated the means through which leishmania could augment activated but not total TGF-beta. Incubation of latent TGF-beta with Leishmania sp. promastigotes caused active TGF-beta to be released from the latent complex. In contrast, the nonpathogenic protozoan Crithidia fasciculata could not activate TGF-beta. TGF-beta activation by leishmania was prevented by inhibitors of cysteine proteases and by the specific cathepsin B inhibitor CA074. Physiologic concentrations of TGF-beta inhibited killing of intracellular L. chagasi in macrophages, although the phagocytosis-induced respiratory burst remained intact. In contrast, supraphysiologic concentrations of TGF-beta had no effect on parasite survival. We hypothesize that the combined effect of abundant TGF-beta stores at extracellular sites during infection, and the ability of the parasite to activate TGF-beta in its local environment, leads to high levels of active TGF-beta in the vicinity of the infected macrophage. Locally activated TGF-beta could, in turn, enhance parasite survival through its effects on innate and adaptive immune responses. 相似文献
69.
Santoro F Greenstone HL Insinga A Liszewski MK Atkinson JP Lusso P Berger EA 《The Journal of biological chemistry》2003,278(28):25964-25969
Human herpesvirus 6 (HHV-6) employs the complement regulator CD46 (membrane cofactor protein) as a receptor for fusion and entry into target cells. Like other known herpesviruses, HHV-6 encodes multiple glycoproteins, several of which have been implicated in the entry process. In this report, we present evidence that glycoprotein H (gH) is the viral component responsible for binding to CD46. Antibodies to CD46 co-immunoprecipitated an approximately 110-kDa protein band specifically associated with HHV-6-infected cells. This protein was identified as gH by selective depletion with an anti-gH monoclonal antibody, as well as by immunoblot analysis with a rabbit hyperimmune serum directed against a gH synthetic peptide. In reciprocal experiments, a monoclonal antibody against HHV-6 gH was found to co-immunoprecipitate CD46. Studies using monoclonal antibodies directed against specific CD46 domains, as well as engineered constructs lacking defined CD46 regions, demonstrated a close correspondence between the CD46 domains involved in the interaction with gH and those previously shown to be critical for HHV-6 fusion (i.e. short consensus repeats 2 and 3). 相似文献
70.