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1.
Clin Exp Immunol ; 185(1): 42-9, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26850369

RESUMO

In humans, CD16 and CD56 are used to identify functionally distinct natural killer (NK) subsets. Due to ubiquitous CD56 expression, this marker cannot be used to distinguish between NK cell subsets in chimpanzees. Therefore, functional analysis of distinct NK subsets during hepatitis C virus (HCV) infection has never been performed in these animals. In the present study an alternative strategy was used to identify four distinct NK subsets on the basis of the expression of CD16 and CD94. The expression of activating and inhibiting surface receptors showed that these subsets resemble human NK subsets. CD107 expression was used to determine degranulation of the different subsets in naive and HCV-infected chimpanzees. In HCV-infected chimpanzees increased spontaneous cytotoxicity was observed in CD94(high/dim) CD16(pos) and CD94(low) CD16(pos) subsets. By contrast, increased natural cytotoxicity receptor (NCR)- mediated degranulation after NKp30 and NKp44 triggering was demonstrated in the CD94(dim) CD16(neg) subset. Our findings suggest that spontaneous and NCR-mediated cytotoxicity are effector functions of distinct NK subsets in HCV-infected chimpanzees.


Assuntos
Linhagem da Célula/imunologia , Citotoxicidade Imunológica , Hepacivirus/imunologia , Hepatite C/imunologia , Células Matadoras Naturais/imunologia , Animais , Doenças dos Símios Antropoides , Degranulação Celular/efeitos dos fármacos , Citometria de Fluxo , Regulação da Expressão Gênica , Hepatite C/patologia , Hepatite C/virologia , Imunofenotipagem , Interleucina-2/farmacologia , Interleucinas/farmacologia , Células Matadoras Naturais/classificação , Células Matadoras Naturais/citologia , Células Matadoras Naturais/efeitos dos fármacos , Ativação Linfocitária/efeitos dos fármacos , Proteína 1 de Membrana Associada ao Lisossomo/genética , Proteína 1 de Membrana Associada ao Lisossomo/imunologia , Subfamília D de Receptores Semelhantes a Lectina de Células NK/genética , Subfamília D de Receptores Semelhantes a Lectina de Células NK/imunologia , Receptor 2 Desencadeador da Citotoxicidade Natural/genética , Receptor 2 Desencadeador da Citotoxicidade Natural/imunologia , Receptor 3 Desencadeador da Citotoxicidade Natural/genética , Receptor 3 Desencadeador da Citotoxicidade Natural/imunologia , Pan troglodytes , Receptores de IgG/genética , Receptores de IgG/imunologia
2.
Clin Exp Immunol ; 174(1): 161-71, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23750720

RESUMO

Macaques provide important animal models in biomedical research into infectious and chronic inflammatory disease. Therefore, a proper understanding of the similarities and differences in immune function between macaques and humans is needed for adequate interpretation of the data and translation to the human situation. Dendritic cells are important as key regulators of innate and adaptive immune responses. Using a new whole blood assay we investigated functional characteristics of blood plasmacytoid dendritic cells (pDC), myeloid dendritic cells (mDC) and monocytes in rhesus macaques by studying induction of activation markers and cytokine expression upon Toll-like receptor (TLR) stimulation. In a head-to-head comparison we observed that rhesus macaque venous blood contained relatively lower numbers of pDC than human venous blood, while mDC and monocytes were present at similar percentages. In contrast to humans, pDC in rhesus macaques expressed the interleukin (IL)-12p40 subunit in response to TLR-7/8 as well as TLR-9 stimulation. Expression of IL-12p40 was confirmed by using different monoclonal antibodies and by reverse transcription-polymerase chain reaction (RT-PCR). Both in humans and rhesus macaques, TLR-4 stimulation induced IL-12p40 expression in mDC and monocytes, but not in pDC. The data show that, in contrast to humans, pDC in macaques are able to express IL-12p40, which could have consequences for evaluation of human vaccine candidates and viral infection.


Assuntos
Células Dendríticas/imunologia , Subunidade p40 da Interleucina-12/biossíntese , Receptor 7 Toll-Like/agonistas , Receptor 7 Toll-Like/sangue , Receptor 8 Toll-Like/agonistas , Receptor 8 Toll-Like/sangue , Receptor Toll-Like 9/agonistas , Receptor Toll-Like 9/sangue , Animais , Células Dendríticas/metabolismo , Humanos , Subunidade p40 da Interleucina-12/sangue , Subunidade p40 da Interleucina-12/genética , Macaca mulatta
3.
Vaccine ; 20(3-4): 304-21, 2001 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-11672892

RESUMO

The severity of the AIDS epidemic clearly emphasises the urgent need to expedite HIV vaccine candidates into clinical trials. Prophylactic HIV vaccine candidates have been evaluated in non-human primates. Based on specific proof of principle studies the first phase III clinical studies have recently begun in humans. However, a truly effective HIV vaccine is not yet at hand and many problems related to specific properties of the virus remain to be overcome. Previously proven empirical approaches have largely failed and now rational thinking based on an understanding of immunity to lentiviral infections is needed. This review addresses the scientific problems and complications facing the development of an HIV vaccine as well as the possible strategies currently available to overcome these problems. Recent attention has focussed on identifying the immune correlates and mechanisms of protection from either HIV infection or protection from disease progression. Based on these observations, the logic and rational behind the development of multiple component vaccine strategies are highlighted.


Assuntos
Vacinas contra a AIDS/imunologia , Vacinas contra a AIDS/administração & dosagem , Vetores Genéticos , HIV/classificação , Humanos , Imunidade nas Mucosas , Vacinas de DNA/imunologia , Vacinas Sintéticas/imunologia
4.
J Infect Dis ; 184(2): 136-43, 2001 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-11424009

RESUMO

Recent evidence suggests a much higher prevalence of human immunodeficiency virus type 1 (HIV-1) recombinants than previously anticipated. These recombinants arise from secondary HIV infections in individuals already infected with the virus. It remains unclear why some individuals acquire secondary HIV-1 infections and others do not. To address this question, a study was undertaken of a small cohort of chimpanzees with well-defined HIV-1 infection. After exposure to an infectious dose of heterologous primary isolate, 4 of 8 HIV-1 seropositive chimpanzees resisted secondary infection, whereas 2 naive controls became readily infected. Only animals who were immunologically boosted were protected. Protection from heterologous secondary exposure appeared to be related to the repertoire of the cytolytic CD8(+) T cell responses to HIV-1. Data suggested that immunologic boosting by HIV-1 antigens or exposure to subinfectious doses of virus may be important events in sustaining sufficient immunity to prevent secondary infections from occurring.


Assuntos
Vacinas contra a AIDS/administração & dosagem , Síndrome da Imunodeficiência Adquirida/imunologia , Síndrome da Imunodeficiência Adquirida/prevenção & controle , Linfócitos T Citotóxicos/imunologia , Vacinas contra a AIDS/imunologia , Animais , Infecções por HIV/imunologia , Pan troglodytes
5.
Ann Neurol ; 47(4): 540-3, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10762171

RESUMO

Recently, 3 patients with a creatine synthesis defect have been described. They presented with developmental regression, extrapyramidal movement abnormalities, and intractable epilepsy, and they improved with treatment of creatine monohydrate. We report 2 unrelated boys with a creatine synthesis defect and nonspecific presenting signs of psychomotor retardation, behavioral problems, and, in 1, mild epilepsy. Metabolic urine screening revealed elevations in all metabolites, expressed as millimoles per mole of creatinine, which suggests decreased creatinine excretion. This finding led to the correct diagnosis. We propose to include the assessment of the overall concentrations of amino acids and organic acids relative to creatinine in routine metabolic urine screening.


Assuntos
Creatina/biossíntese , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/metabolismo , Transtornos Mentais/diagnóstico , Transtornos Mentais/metabolismo , Ácido Aspártico/análogos & derivados , Ácido Aspártico/análise , Líquidos Corporais/química , Encefalopatias Metabólicas/diagnóstico , Encefalopatias Metabólicas/tratamento farmacológico , Encefalopatias Metabólicas/metabolismo , Pré-Escolar , Creatina/administração & dosagem , Creatina/urina , Diagnóstico Diferencial , Epilepsia/diagnóstico , Epilepsia/metabolismo , Seguimentos , Glicina/análogos & derivados , Glicina/análise , Humanos , Lactente , Deficiência Intelectual/tratamento farmacológico , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Masculino , Transtornos Mentais/tratamento farmacológico
6.
J Inherit Metab Dis ; 23(1): 77-82, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10682310

RESUMO

This retrospective study in 20 untreated type I Gaucher disease patients shows that in Dutch patients clinical manifestations of Gaucher disease type I are progressive in the majority of patients, children as well as adults. This is in contrast with studies among Jewish patients. Our results emphasize the need for a regular follow-up to enable timely initiation of enzyme therapy.


Assuntos
Doença de Gaucher/complicações , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
7.
J Virol ; 74(9): 4017-27, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10756013

RESUMO

Current strategies in human immunodeficiency virus type 1 (HIV-1) vaccine development are often based on the production of different vaccine antigens according to particular genetic clades of HIV-1 variants. To determine if virus virulence or genetic distance had a greater impact on HIV-1 vaccine efficacy, we designed a series of heterologous chimeric simian/human immunodeficiency virus (SHIV) challenge experiments in HIV-1 subunit-vaccinated rhesus macaques. Of a total of 22 animals, 10 nonimmunized animals served as controls; the remainder were vaccinated with the CCR5 binding envelope of HIV-1(W6.1D). In the first study, heterologous challenge included two nonpathogenic SHIV chimeras encoding the envelopes of the divergent clade B HIV-1(han2) and HIV-1(sf13) strains. In the second study, all immunized animals were rechallenged with SHIV(89. 6p), a virus closely related to the vaccine strain but highly virulent. Protection from either of the divergent SHIV(sf13) or SHIV(han2) challenges was demonstrated in the majority of the vaccinated animals. In contrast, upon challenge with the more related but virulent SHIV(89.6p), protection was achieved in only one of the previously protected vaccinees. A secondary but beneficial effect of immunization on virus load and CD4(+) T-cell counts was observed despite failure to protect from infection. In addition to revealing different levels of protective immunity, these results suggest the importance of developing vaccine strategies capable of protecting from particularly virulent variants of HIV-1.


Assuntos
Vacinas contra a AIDS/imunologia , Infecções por HIV/prevenção & controle , HIV-1/imunologia , HIV-1/patogenicidade , Animais , Modelos Animais de Doenças , Proteína gp120 do Envelope de HIV/genética , Proteína gp120 do Envelope de HIV/imunologia , Proteína gp41 do Envelope de HIV/genética , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Macaca mulatta , Vírus da Imunodeficiência Símia/genética , Vacinas Atenuadas/imunologia , Virulência
8.
J Med Primatol ; 28(4-5): 224-32, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10593489

RESUMO

In two previous studies, we have demonstrated the successful protection of human immunodeficiency virus type 1 (HIV-1)-vaccinated rhesus macaques from challenge with SHIV(SF13) with envelop immunogens derived from the closely related HIV-1(SF2) strain. Here we report on two follow-up studies in which we aimed to broaden immunity in order to elicit protection from a more diverse heterologous challenge with SHIV(SF33). In the first study, animals were boosted once with HIV-1(SF33) V2 and V3 peptides that were cross-linked to influenza immune-stimulating complexes (ISCOMs). In the second study, monkeys were boosted twice at 12-week intervals, using a heterologous recombinant gp120 derived from HIV-1(SF33) that was either incorporated into ISCOMs or mixed with the MF59 adjuvant. In both studies, the animals were challenged with 50 monkey infectious doses of SHIV(SF33) 4 weeks after the final boost. All controls became readily infected with the heterologous challenge virus SHIV(SF33). Neither boosting with heterologous SF33 peptides or gp120 afforded protection from infection to SF2-vaccinated animals that had previously resisted SHIV(SF13) challenge. These results demonstrate the importance of developing vaccine strategies that are capable of generating broad immune responses early in the immunization protocol. Furthermore, these findings may illustrate the potential pitfalls of early antigenic sin.


Assuntos
Vacinas contra a AIDS/imunologia , HIV-1/imunologia , Proteínas do Envelope Viral/imunologia , Animais , Epitopos/imunologia , Proteína gp120 do Envelope de HIV/imunologia , Imunização/veterinária , Macaca mulatta , Orthomyxoviridae/imunologia , Fragmentos de Peptídeos/imunologia , Vírus da Imunodeficiência Símia/imunologia , Vacinas Atenuadas/imunologia , Carga Viral
9.
J Med Genet ; 36(3): 253-7, 1999 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10204857

RESUMO

Little is known about the mechanism of CGG instability and the time frame of instability early in embryonic development in the fragile X syndrome. Discordant monozygotic twin brothers with the fragile X syndrome could give us insight into the time frame of the instability. We describe monochorionic diamniotic twin brothers with the fragile X syndrome who had different CGG repeats and different mental capacities, whereas the normal mother had a premutation. The more retarded brother had a full mutation in all his cells and no FMR-1 protein expression in lymphocytes, whereas the less retarded brother had 50%/50% mosaicism for a premutation and full mutation and FMR-1 protein expression in 26% of his lymphocytes. The differences in repeat size could have arisen either before or after the time of splitting. The time of splitting in this type of twin is around day 6-7. Given the high percentage of mosaicism, we hypothesise that the instability started before the time of splitting at day 6-7.


Assuntos
Síndrome do Cromossomo X Frágil/genética , Proteínas do Tecido Nervoso/genética , Proteínas de Ligação a RNA , Repetições de Trinucleotídeos , Gêmeos Monozigóticos/genética , Pré-Escolar , Metilação de DNA , Feminino , Proteína do X Frágil da Deficiência Intelectual , Síndrome do Cromossomo X Frágil/metabolismo , Síndrome do Cromossomo X Frágil/psicologia , Humanos , Masculino , Mutagênese , Proteínas do Tecido Nervoso/metabolismo , Linhagem
10.
Immunol Lett ; 66(1-3): 61-7, 1999 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10203035

RESUMO

Cell mediated immune responses to HIV-1 and CTL responses in particular differ dramatically in infected individuals. This may largely be influenced by the immunogenetic differences of different individuals such as those encoded by the MHC. These differences may be difficult to dissect due to the immunosuppressive nature of HIV-1 infection itself. In order to reduce the variables associated with effects of the virus, one recombinant viral antigen was chosen from a particular HIV-1 variant (rgp120 of the clinical isolate HIV-1w6.1D). To minimise differences between outbred hosts, we chose two sibling chimpanzees from which the family pedigree and genetic segregation with respect to polymorphic MHC molecules was known. Immunisation induced strong antigen specific antibody and T-helper immune responses. The magnitude and persistence of the humoral and T-helper immune responses were comparable in both chimpanzees. However, CTL responses were only observed in one sibling. These responses were subsequently mapped to several distinct epitopes. The CTL response to the immunodominant epitope was found to be presented in the context of a MHC molecule which was shared by both siblings. The absence of a CTL response in the other sibling is not yet understood, but could not be attributed to MHC alleles that were not shared by these two chimpanzees. These findings suggest that other polymorphic immunoregulatory mechanisms such as those involved in antigen processing and presentation influence host CTL responses to HIV-1.


Assuntos
HIV-1/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Linfócitos T Citotóxicos/imunologia , Animais , Mapeamento de Epitopos , Epitopos de Linfócito T/imunologia , Feminino , Haplótipos , Humanos , Masculino , Pan troglodytes , Linhagem
11.
Immunol Lett ; 66(1-3): 189-95, 1999 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10203054

RESUMO

The specific immune mechanisms necessary and/or sufficient to elicit HIV-vaccine protection remain undefined. Utilising the SHIV rhesus macaque model the immunogenicity as well as the efficacy of ten different HIV-1 vaccine candidates was evaluated. Comparison of the immune responses induced, with the ability of the vaccine to protect from SHIV infection provided a means to determine which type of immune responses were necessary for protection. Vaccine candidates included VLPs, DNA, subunit protein with novel adjuvant formulations, ISCOMs and pox-virus vectors. Protection from SHIV infection was achieved in approximately half of the animals which received a primary intravenous cell-free challenge. The presence of CTL in the absence of other effector responses did not correlate with protection from this route and type of challenge. Virus neutralising antibodies (Nab) appeared to be necessary but alone were insufficient for protection. If Ag-specific IFN-gamma and/or IL-4 as well as lymphoproliferative (LP) responses were found with the lack of a detectable IL-2 response, then protection was not observed. Immunity correlated with the magnitude of Nab responses, beta-chemokines and as well as balanced, qualitative T-helper responses.


Assuntos
Vacinas contra a AIDS/imunologia , HIV-1/imunologia , Vírus Reordenados/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Vírus da Imunodeficiência Símia/imunologia , Animais , Formação de Anticorpos , Quimiocinas CC/imunologia , Ensaios Clínicos como Assunto , Anticorpos Anti-HIV/imunologia , Humanos , Imunidade Celular , Macaca mulatta , Testes de Neutralização , Linfócitos T Citotóxicos/imunologia , Linfócitos T Auxiliares-Indutores/imunologia
12.
J Virol ; 73(4): 3292-300, 1999 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10074183

RESUMO

The kinetics of T-helper immune responses generated in 16 mature outbred rhesus monkeys (Macaca mulatta) within a 10-month period by three different human immunodeficiency virus type 1 (HIV-1) vaccine strategies were compared. Immune responses to monomeric recombinant gp120SF2 (rgp120) when the protein was expressed in vivo by DNA immunization or when it was delivered as a subunit protein vaccine formulated either with the MF59 adjuvant or by incorporation into immune-stimulating complexes (ISCOMs) were compared. Virus-neutralizing antibodies (NA) against HIV-1SF2 reached similar titers in the two rgp120SF2 protein-immunized groups, but the responses showed different kinetics, while NA were delayed and their levels were low in the DNA-immunized animals. Antigen-specific gamma interferon (IFN-gamma) T-helper (type 1-like) responses were detected in the DNA-immunized group, but only after the fourth immunization, and the rgp120/MF59 group generated both IFN-gamma and interleukin-4 (IL-4) (type 2-like) responses that appeared after the third immunization. In contrast, rgp120/ISCOM-immunized animals rapidly developed marked IL-2, IFN-gamma (type 1-like), and IL-4 responses that peaked after the second immunization. To determine which type of immune responses correlated with protection from infection, all animals were challenged intravenously with 50 50% infective doses of a rhesus cell-propagated, in vivo-titrated stock of a chimeric simian immunodeficiency virus-HIVSF13 construct. Protection was observed in the two groups receiving the rgp120 subunit vaccines. Half of the animals in the ISCOM group were completely protected from infection. In other subunit vaccinees there was evidence by multiple assays that virus detected at 2 weeks postchallenge was effectively cleared. Early induction of potent type 1- as well as type 2-like T-helper responses induced the most-effective immunity.


Assuntos
Vacinas contra a AIDS/imunologia , Síndrome da Imunodeficiência Adquirida/imunologia , Proteína gp120 do Envelope de HIV/imunologia , HIV-1/imunologia , ISCOMs/imunologia , Imunidade Celular , Polissorbatos/farmacologia , Esqualeno/imunologia , Esqualeno/farmacologia , Vacinas contra a AIDS/química , Vacinas contra a AIDS/farmacologia , Síndrome da Imunodeficiência Adquirida/prevenção & controle , Adjuvantes Imunológicos/farmacologia , Animais , Química Farmacêutica , Proteína gp120 do Envelope de HIV/farmacologia , Humanos , ISCOMs/farmacologia , Macaca mulatta , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/farmacologia
13.
J Immunol ; 162(4): 2308-14, 1999 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-9973508

RESUMO

Certain HIV-1 infected humans that do not progress to AIDS have been documented to share particular MHC class I alleles that appear to correlate with long-term survival. HIV-1-infected chimpanzees are relatively resistant to progression to AIDS. Out of a group of 10 chimpanzees with CTL activity and nonprogressive HIV-1 infection, 2 animals with prominent cytolytic CD3+CD8+ T cell responses to HIV-1 Ags were studied in detail. Characterization of these CTL revealed that they contained the granzymes A and B, T cell intracellular Ag-1, and perforin and induced calcium-dependent cytolysis that correlated with the presence of apoptotic nuclei in target cells. These CTL responses were directed against two gagpeptides, which were found to be identical to previously described epitopes recognized in the context of HLA-B27 and HLA-B57 molecules. The latter two restriction elements occur with increased frequency in human long-term survivor cohorts. Phylogenetic comparisons revealed that the chimpanzee restriction elements, Patr-B*02and -B*03, described here do not show any obvious similarity with the HLA-B*27 and -B*57 alleles, suggesting that CTL responses to HIV-1 in distinct primate species may be controlled by different types of HLA-B-like molecules. The CTL responses in these two chimpanzees are directed, however, against highly conserved epitopes mapping across the majority of HIV-1 clades.


Assuntos
Síndrome da Imunodeficiência Adquirida/imunologia , Sequência Conservada/imunologia , Epitopos de Linfócito T/metabolismo , Sobreviventes de Longo Prazo ao HIV , HIV-1/imunologia , Pan troglodytes/imunologia , Linfócitos T Citotóxicos/imunologia , Síndrome da Imunodeficiência Adquirida/genética , Síndrome da Imunodeficiência Adquirida/veterinária , Sequência de Aminoácidos , Animais , Citotoxicidade Imunológica/genética , Mapeamento de Epitopos , Epitopos de Linfócito T/genética , Epitopos de Linfócito T/isolamento & purificação , Produtos do Gene gag/imunologia , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Imunofenotipagem , Dados de Sequência Molecular , Doenças dos Primatas/genética , Doenças dos Primatas/imunologia , Linfócitos T Citotóxicos/química , Linfócitos T Citotóxicos/metabolismo
14.
Ned Tijdschr Geneeskd ; 142(4): 169-74, 1998 Jan 24.
Artigo em Holandês | MEDLINE | ID: mdl-9557021

RESUMO

The first report of a positive effect of allogeneic bone marrow transplantation (BMT) on the clinical course in a patient with a lysosomal storage disease was described in 1981. Since then, over 200 patients have been treated in this way but data are scarce and fragmentary. Allogeneic BMT involves replacement of the patient's haemopoietic system by that of a donor. The new cells that repopulate the body can correct the metabolic disturbance. Most experience with allogeneic BMT was gained in patients with mucopolysaccharidosis type I, metachromatic leukodystrophy and adrenoleukodystrophy. Allogeneic BMT reduces the amount of storage material in internal organs: skeletal abnormalities and neurological symptoms are at best stabilized. Transplantation-related mortality and morbidity are high. The applicability of allogeneic BMT is limited.


Assuntos
Transplante de Medula Óssea , Doenças por Armazenamento dos Lisossomos/terapia , Adrenoleucodistrofia/terapia , Adulto , Transplante de Medula Óssea/mortalidade , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Leucodistrofia Metacromática/terapia , Masculino , Mucopolissacaridose I/terapia , Resultado do Tratamento
15.
AIDS ; 12(5): F15-22, 1998 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-9543435

RESUMO

OBJECTIVES: To investigate whether immunization with recombinant HIV-1 envelope protein derived from a clinical isolate could protect macaques from infection with an in vivo passaged chimeric simian-human immunodeficiency virus (SHIV). DESIGN AND METHODS: A total of 16 animals were studied from which three groups of four animals were immunized with vaccine formulations of the CC-chemokine receptor-5-binding recombinant gp120 of HIV-1W6.1D. Four weeks after the last immunization, all 16 animals were intravenously challenged with in vivo passaged SHIV derived from the same HIV-1 group B clinical isolate (W6.1D) as the vaccines. RESULTS: Vaccine protection from infection was demonstrated in 10 out of 12 macaques immunized with recombinant gp120. Complete protection from infection was achieved with all of the animals that received the SBAS2-W6.1D formulation, a potent inducer of both T-cell and humoral immune responses. Partial protection was achieved with SBAS1-W6.1D, a formulation based on immunomodulators known to induce T-cell responses in humans. In vaccinated animals that were infected, virus load was reduced and infection was delayed. CONCLUSIONS: In a relatively large number of primates, vaccine efficacy was demonstrated with a clinically relevant HIV-1 vaccine. These results reveal that it is possible to induce sterilizing immunity sufficient to protect from infection with SHIV which was passaged multiple times in vivo. Our findings have implications for current HIV-1 clinical vaccine trials and ongoing efforts to develop safe prophylactic AIDS vaccines.


Assuntos
Vacinas contra a AIDS , Proteína gp120 do Envelope de HIV/imunologia , Infecções por HIV/prevenção & controle , HIV-1/imunologia , Vírus da Imunodeficiência Símia/imunologia , Vacinas Sintéticas , Vacinas contra a AIDS/imunologia , Animais , Afinidade de Anticorpos , Quimera , Anticorpos Anti-HIV/biossíntese , Infecções por HIV/imunologia , Imunidade Celular , Macaca mulatta , Testes de Neutralização , Reação em Cadeia da Polimerase , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Vírus da Imunodeficiência Símia/genética , Vacinação , Vacinas Sintéticas/imunologia
17.
J Pediatr ; 128(5 Pt 1): 679-83, 1996 May.
Artigo em Inglês | MEDLINE | ID: mdl-8627441

RESUMO

An infant with feeding difficulties, hypotonia, lactic acidemia, and severe hypoketotic hypoglycemia died at the age of 7 months of liver disease. Electron microscopy revealed abnormal mitochondria. Biochemical studies of mitochondrial enzymes in liver showed a decreased activity of complexes I, III, and IV. Mitochondrial DNA (mtDNA) content was reduced in liver 7% of the mean value in control subjects) and in muscle (50%). In kidney, brain, and heart, the mtDNA content was normal. The liver-specific mtDNA depletion syndrome in this patient manifested itself with features of both a respiratory chain defect and a mitochondrial fatty acid oxidation defect. Syndromes involving depletion of mtDNA can be diagnosed only when the activity of the respiratory chain enzymes and the content of mtDNA are investigated in the most affected tissues.


Assuntos
Acidose Láctica/complicações , DNA Mitocondrial/isolamento & purificação , Hipoglicemia/complicações , Falência Hepática/metabolismo , Transporte de Elétrons , Evolução Fatal , Humanos , Lactente , Falência Hepática/enzimologia , Falência Hepática/etiologia , Falência Hepática/patologia , Masculino , Mitocôndrias Hepáticas/enzimologia , Mitocôndrias Hepáticas/genética , Oxirredutases/metabolismo
19.
J Pediatr ; 124(5 Pt 1): 748-50, 1994 May.
Artigo em Inglês | MEDLINE | ID: mdl-8176565

RESUMO

We treated five children with Sjögren-Larsson syndrome. The patients, 5 months to 8 years of age, were given a low fat diet supplemented with medium-chain fatty acids. Plasma octadecanol levels remained unchanged, and skin lesions and neurologic symptoms did not abate. Two patients also failed to respond to dietary supplementation with polyunsaturated fatty acids. We conclude that dietary therapy is usually unsuccessful in patients with Sjögren-Larsson syndrome even when started in early infancy.


Assuntos
Ácidos Graxos Essenciais/uso terapêutico , Síndrome de Sjogren-Larsson/dietoterapia , Pré-Escolar , Gorduras na Dieta/administração & dosagem , Feminino , Humanos , Lactente , Recém-Nascido , Ácidos Linoleicos , Masculino , Oenothera biennis , Óleos de Plantas , Falha de Tratamento , Ácido gama-Linolênico
20.
J Endocrinol ; 140(3): 503-12, 1994 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8182378

RESUMO

Stimulation of human peripheral blood monocytes with the thyroid hormones tri-iodothyronine (T3) and thyroxine (T4) enhanced their ability to mature into cytologically and functionally characteristic veiled/dendritic cells. Veiled/dendritic cell transition induced by T3 and T4 was dependent on the production of granulocyte-macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor-alpha (TNF alpha) and interleukin-6 (IL-6) in the culture, since the addition of antibodies specific for GM-CSF, TNF alpha and IL-6 to the culture system had blocking effects. The addition of antibodies to macrophage colony-stimulating factor and IL-1 had no effects. Contaminating T cells and B cells did not contribute to the transition of monocytes to veiled/dendritic cells, and it is therefore likely that the GM-CSF, TNF alpha and IL-6 produced in the culture system were derived from the monocytes themselves. Stimulation of the blood monocytes with an optimal concentration of metrizamide (14.5%), reverse T3 (rT3; 2 x 10(-10) M) or highly iodinated thyroglobulin (Tg; 2 x 10(-11) M) also resulted in an increased transition of monocytes to veiled/dendritic cells, but to a lesser extent in comparison with the thyroid hormones (T3, 31 +/- 6% and T4, 25 +/- 5% vs rT3, 22 +/- 8% and Tg with an iodination grade of 0.37%: 20 +/- 4% veiled/dendritic cells). Administration of anti-GM-CSF, anti-TNF alpha and anti-IL-6 to the culture system also had blocking effects on the transition from monocytes to veiled/dendritic cells induced by the iodinated compounds. The mechanisms by which such iodinated compounds act on the monocyte to veiled/dendritic cell transition can only be speculated on (interference H2O2-generating system?).


Assuntos
Citocinas/farmacologia , Células Dendríticas/citologia , Monócitos/citologia , Hormônios Tireóideos/farmacologia , Anticorpos Monoclonais/farmacologia , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Humanos , Interleucina-6/imunologia , Interleucina-6/farmacologia , Metrizamida/farmacologia , Estimulação Química , Tireoglobulina/farmacologia , Tri-Iodotironina Reversa/farmacologia , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/farmacologia
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