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1.
Dig Liver Dis ; 40(8): 690-6, 2008 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-18337194

RESUMEN

BACKGROUND: Percutaneous drainage of pyogenic liver abscess has become first-line treatment. In the past surgical drainage was preferred in some centres. AIM: The aim of this retrospective study was to assess the effectiveness of percutaneous treatments and surgical drainage, in terms of treatment success, hospital stay and costs. PATIENTS: Data of 148 patients (90 males; 58 females; mean age, 61 yrs; range, 30-86 yrs) were retrospectively analysed. METHODS: Patients' outcomes, including the length of hospital stay, procedure-related complications, treatment failure and death, were recorded. Multiple logistic regression model was used for statistical analysis. RESULTS: One hundred and four patients (83 with solitary and 21 with multiple abscesses) were treated percutaneously, either by needle aspiration (91 patients) or catheter drainage (13 patients) depending on the abscess's size, and 44 patients (30 with solitary and 14 with multiple abscesses) were treated surgically. There was no statistically significant difference in patients' demographics or abscess characteristics between groups. Hospital stay was longer, and costs were higher in patients treated surgically (p<0.001). There was statistically significant difference in morbidity rate between groups (p<0.001). No death occurred in both groups. CONCLUSIONS: Percutaneous and surgical treatment of pyogenic liver abscesses are both effective, nevertheless percutaneous drainage carries lower morbidity and is cheaper.


Asunto(s)
Drenaje/métodos , Absceso Piógeno Hepático/terapia , Adulto , Anciano , Anciano de 80 o más Años , Drenaje/economía , Drenaje/estadística & datos numéricos , Femenino , Humanos , Tiempo de Internación , Absceso Piógeno Hepático/epidemiología , Absceso Piógeno Hepático/cirugía , Masculino , Persona de Mediana Edad , Morbilidad , Punciones , Estudios Retrospectivos , Resultado del Tratamiento
2.
Ultraschall Med ; 27(1): 20-33, 2006 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-16470476

RESUMEN

Patients with AIDS present a wide variety of clinical manifestations through involvement of various organs. Ultrasonography (US) is easy to perform, safe, inexpensive, not invasive and repeatable. Those features are crucial for AIDS patients, who in industrialised countries are now mostly seen on an outpatient basis thanks to the introduction of Highly Active Antiretroviral Therapy. US can investigate most of the organs affected in AIDS and can guide biopsies, allowing the cyto-histological and microbiological investigations needed for a definitive diagnosis. This paper reviews the wide variety of applications of abdominal US and stresses its importance in the management of a complex and changing condition, particularly in settings where other more expensive imaging techniques are not--and will not be for a long time--available. The increasing use of portable/hand-carried scanners further adds to the value of the technique in such settings. With new treatments, prevalence and morbidity/mortality rates change, but new conditions and new side effects appear. US applications to these new conditions are discussed as well.


Asunto(s)
Abdomen/diagnóstico por imagen , Síndrome de Inmunodeficiencia Adquirida/diagnóstico por imagen , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Humanos , Hepatopatías/diagnóstico por imagen , Hepatopatías/etiología , Linfoma Relacionado con SIDA/diagnóstico por imagen , Sarcoma de Kaposi/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Ultrasonografía
4.
Parassitologia ; 46(1-2): 53-5, 2004 Jun.
Artículo en Italiano | MEDLINE | ID: mdl-15305686

RESUMEN

Surgical excision of echinococcal cyst has long been considered the only effective treatment for echinococcosis. However, the remarkable advances in imaging techniques, particularly ultrasound, made during the past 25 years have greatly facilitated diagnosis, treatment and follow-up. Today, chemotherapy and percutaneous treatments have become widely available. A major step forward in management of the disease came in 2001, when the WHO International Working Group on Echinococcosis (WHO-IWGE) came to a consensus by developing a standardized classification of ultrasound images in cystic echinococcosis. Thus, the most appropriate treatment for patients affected by this serious and sometimes life-threatening disease may now be chosen. An overview of the three main therapeutic options for abdominal- and particularly hepatic-cystic echinococcosis is presented, with focus on the indications and contraindications of each one. Data from long-term follow-up studies are also discussed, with emphasis on the resulting stage-specific criteria for treatment.


Asunto(s)
Equinococosis/terapia , Albendazol/uso terapéutico , Antihelmínticos/uso terapéutico , Ablación por Catéter , Drenaje , Equinococosis/diagnóstico por imagen , Equinococosis/tratamiento farmacológico , Equinococosis/cirugía , Hepatectomía/métodos , Humanos , Laparoscopía/métodos , Mebendazol/uso terapéutico , Ultrasonografía Intervencional
5.
Parassitologia ; 46(4): 367-70, 2004 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-16044692

RESUMEN

Image-guided percutaneous treatments for echinococcal cysts were introduced in the mid-eighties. Today they represent a third therapeutic option, after surgery and benzimidazole derivatives. Two types of percutaneous treatments are available, based on the destruction of the germinal layer or the evacuation of the endocyst. To assess the extent of their use and their safety, a Medline search of the literature on this subject was performed. The number of cysts treated, their anatomical sites, the complications and, length of follow-up (when available), were all examined. The results show that percutaneous treatments for cystic echinococcosis are safe and efficacious in selected anatomical sites, provided basic safety issues are correctly addressed. However, before drawing final conclusions, a more detailed analysis of the literature is needed. Percutaneous treatments could be simplified and made more effective if a scolecidal agent could be found that melts the entire endocyst without causing harm to the biliary epithelium.


Asunto(s)
Antihelmínticos/uso terapéutico , Ablación por Catéter , Equinococosis/cirugía , Succión , Anafilaxia/etiología , Animales , Antihelmínticos/administración & dosificación , Fístula Biliar/etiología , Ablación por Catéter/efectos adversos , Ablación por Catéter/instrumentación , Ensayos Clínicos como Asunto , Terapia Combinada , Equinococosis/tratamiento farmacológico , Equinococosis Hepática/tratamiento farmacológico , Equinococosis Hepática/cirugía , Echinococcus granulosus/efectos de los fármacos , Echinococcus granulosus/crecimiento & desarrollo , Estudios de Seguimiento , Humanos , Inyecciones Intralesiones , Larva , Tiempo de Internación , Absceso Hepático/etiología , Complicaciones Posoperatorias , Recurrencia , Succión/efectos adversos , Succión/instrumentación
6.
Immunity ; 10(4): 431-8, 1999 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-10229186

RESUMEN

Neutralizing antibodies can protect against challenge with HIV-1 in vivo if present at appropriate concentrations at the time of viral challenge, but any role in the control of established infection is unclear. Here, we show that high serum concentrations of neutralizing monoclonal antibodies, either singly or as a cocktail, have little sustained effect on viral load in established HIV-1 infection in hu-PBL-SCID mice. In some instances, virus replication of neutralization-sensitive virus continues even in the presence of high levels of neutralizing antibody. In most instances, neutralization escape occurs in a few days, even from a cocktail of three antibodies that recognize distinct epitopes. The results imply that humoral immunity is unlikely to play a significant role in the control of established HIV-1 infection in humans.


Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Infecciones por VIH/inmunología , Infecciones por VIH/prevención & control , VIH-1/inmunología , Animales , Quimera/genética , Quimera/inmunología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta Inmunológica , Femenino , Productos del Gen env/genética , Infecciones por VIH/genética , Infecciones por VIH/virología , VIH-1/genética , Humanos , Inyecciones Intraperitoneales , Cinética , Masculino , Ratones , Ratones SCID , Pruebas de Neutralización , Mutación Puntual/inmunología , Inmunodeficiencia Combinada Grave/sangre , Inmunodeficiencia Combinada Grave/genética , Inmunodeficiencia Combinada Grave/inmunología , Inmunodeficiencia Combinada Grave/virología , Replicación Viral/genética , Replicación Viral/inmunología
7.
J Virol ; 73(5): 3544-50, 1999 May.
Artículo en Inglés | MEDLINE | ID: mdl-10196243

RESUMEN

The natural ligands for the CCR5 chemokine receptor, macrophage inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, and RANTES (regulated on T-cell activation, normal T-cell expressed and secreted), are known to inhibit human immunodeficiency virus (HIV) entry, and N-terminally modified RANTES analogues are more potent than native RANTES in blocking infection. However, potent CCR5 blocking agents may select for HIV-1 variants that use alternative coreceptors at less than fully inhibitory concentrations. In this study, two N-terminal chemical modifications of RANTES produced by total synthesis, aminooxypentane (AOP)-RANTES[2-68] and N-nonanoyl (NNY)-RANTES[2-68], were tested for their ability to prevent HIV-1 infection and to select for coreceptor switch variants in the human peripheral blood lymphocyte-SCID mouse model. Mice were infected with a CCR5-using HIV-1 isolate that requires only one or two amino acid substitutions to use CXCR4 as a coreceptor. Even though it achieved lower circulating concentrations than AOP-RANTES (75 to 96 pM as opposed to 460 pM under our experimental conditions), NNY-RANTES was more effective in preventing HIV-1 infection. However, in a subset of treated mice, these levels of NNY-RANTES rapidly selected viruses with mutations in the V3 loop of envelope that altered coreceptor usage. These results reinforce the case for using agents that block all significant HIV-1 coreceptors for effective therapy.


Asunto(s)
Fármacos Anti-VIH/farmacología , Quimiocina CCL5/análogos & derivados , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , Receptores CCR5/metabolismo , Receptores CXCR4/metabolismo , Secuencia de Aminoácidos , Animales , Fármacos Anti-VIH/síntesis química , Quimiocina CCL5/síntesis química , Quimiocina CCL5/farmacología , Modelos Animales de Enfermedad , Variación Genética , Infecciones por VIH/inmunología , Infecciones por VIH/metabolismo , VIH-1/genética , VIH-1/metabolismo , Humanos , Ratones , Ratones SCID , Datos de Secuencia Molecular , Homología de Secuencia de Aminoácido
8.
Proc Natl Acad Sci U S A ; 95(22): 12890-5, 1998 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-9789010

RESUMEN

Sequence-specific DNA-binding small molecules that can permeate human cells potentially could regulate transcription of specific genes. Multiple cellular DNA-binding transcription factors are required by HIV type 1 for RNA synthesis. Two pyrrole-imidazole polyamides were designed to bind DNA sequences immediately adjacent to binding sites for the transcription factors Ets-1, lymphoid-enhancer binding factor 1, and TATA-box binding protein. These synthetic ligands specifically inhibit DNA-binding of each transcription factor and HIV type 1 transcription in cell-free assays. When used in combination, the polyamides inhibit virus replication by >99% in isolated human peripheral blood lymphocytes, with no detectable cell toxicity. The ability of small molecules to target predetermined DNA sequences located within RNA polymerase II promoters suggests a general approach for regulation of gene expression, as well as a mechanism for the inhibition of viral replication.


Asunto(s)
Proteínas de Unión al ADN/metabolismo , VIH-1/genética , Oligodesoxirribonucleótidos/farmacología , ARN Polimerasa II/antagonistas & inhibidores , TATA Box , Factores de Transcripción/metabolismo , Transcripción Genética/efectos de los fármacos , Replicación Viral/efectos de los fármacos , Secuencia de Bases , Sitios de Unión , Línea Celular , Sistema Libre de Células , VIH-1/fisiología , Células HeLa , Humanos , Ligandos , Linfocitos , Conformación de Ácido Nucleico , Oligodesoxirribonucleótidos/química , Proteínas Recombinantes/metabolismo , Secuencias Reguladoras de Ácidos Nucleicos , Proteína de Unión a TATA-Box , Factores de Transcripción/antagonistas & inhibidores
9.
J Virol ; 72(3): 2002-9, 1998 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-9499054

RESUMEN

Most individuals infected with human immunodeficiency virus type 1 (HIV-1) initially harbor macrophage-tropic, non-syncytium-inducing (M-tropic, NSI) viruses that may evolve into T-cell-tropic, syncytium-inducing viruses (T-tropic, SI) after several years. The reasons for the more efficient transmission of M-tropic, NSI viruses and the slow evolution ofT-tropic, SI viruses remain unclear, although they may be linked to expression of appropriate chemokine coreceptors for virus entry. We have examined plasma viral RNA levels and the extent of CD4+ T-cell depletion in SCID mice reconstituted with human peripheral blood leukocytes following infection with M-tropic, dual-tropic, or T-tropic HIV-1 isolates. The cell tropism was found to determine the course of viremia, with M-tropic viruses producing sustained high viral RNA levels and sparing some CD4+ T cells, dual-tropic viruses producing a transient and lower viral RNA spike and extremely rapid depletion of CD4+ T cells, and T-tropic viruses causing similarly lower viral RNA levels and rapid-intermediate rates of CD4+ T-cell depletion. A single amino acid change in the V3 region of gp120 was sufficient to cause one isolate to switch from M-tropic to dual-tropic and acquire the ability to rapidly deplete all CD4+ T cells.


Asunto(s)
Linfocitos T CD4-Positivos/virología , Infecciones por VIH/virología , VIH-1/fisiología , Macrófagos/virología , Viremia , Animales , Modelos Animales de Enfermedad , Infecciones por VIH/sangre , VIH-1/genética , VIH-1/aislamiento & purificación , Humanos , Cinética , Leucocitos Mononucleares/virología , Ratones , Ratones SCID , ARN Viral/biosíntesis , Replicación Viral
10.
Virology ; 238(1): 22-9, 1997 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-9375005

RESUMEN

The body-cavity-based lymphoma cell line BCBL-1, which is infected with Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8, was injected alone or with human peripheral blood mononuclear cells into SCID mice. Immunoblastic lymphomas developed at or near the site of injection. The lymphomas appeared to derive exclusively from the injected BCBL-1 cells and not from the injected human PBMC. The tumors elicited a marked murine angiogenic response, but known angiogenic cytokines were not detected in BCBL-1 cells. Transfer of BCBL-1 cells to SCID mice may represent an in vivo model for the study of KSHV/HHV8-stimulated angiogenesis.


Asunto(s)
Infecciones por Herpesviridae/virología , Herpesvirus Humano 8/fisiología , Transfusión de Linfocitos , Leucemia-Linfoma Linfoblástico de Células Precursoras/virología , Animales , Antígenos CD/análisis , Citocinas/biosíntesis , Regulación Neoplásica de la Expresión Génica , Infecciones por Herpesviridae/inmunología , Infecciones por Herpesviridae/patología , Humanos , Inmunofenotipificación , Interleucinas/biosíntesis , Linfocitos/virología , Ratones , Ratones SCID , Neovascularización Patológica , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Sarcoma de Kaposi/virología , Trasplante Heterólogo , Células Tumorales Cultivadas
11.
J Virol ; 71(9): 7124-7, 1997 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-9261448

RESUMEN

Individuals homozygous for a 32-bp deletion (delta 32) in the CCR5 gene encoding the coreceptor for macrophage-tropic human immunodeficiency virus type 1 (HIV-1) are resistant to virus infection, and heterozygous individuals show some slowing of disease progression. The impact of the CCR5 genotype on HIV-1 infection was assessed in vitro and in the human PBL-SCID (hu-PBL-SCID) model. Cells and hu-PBL-SCID mice from CCR5 delta 32/delta 32 donors were resistant to infection with macrophage-tropic HIV-1 and showed slower replication of dual-tropic HIV-1. hu-PBL-SCID mice derived from CCR5 delta 32/+ heterozygotes showed delayed replication of macrophage-tropic HIV-1 despite a small and variable effect of heterozygosity on viral replication in vitro. The level of CCR5 expression appears to limit replication of macrophage-tropic and dual-tropic HIV-1 strains in vivo.


Asunto(s)
VIH-1/fisiología , Receptores de Citocinas/genética , Receptores de Citocinas/metabolismo , Receptores del VIH/genética , Receptores del VIH/metabolismo , Secuencia de Aminoácidos , Animales , Secuencia de Bases , ADN , Genotipo , Proteína p24 del Núcleo del VIH/análisis , VIH-1/metabolismo , Humanos , Cinética , Ratones , Ratones SCID , Datos de Secuencia Molecular , ARN Viral , Receptores CCR5
12.
J Virol ; 71(5): 4161-4, 1997 May.
Artículo en Inglés | MEDLINE | ID: mdl-9094701

RESUMEN

The pathogenicity of four human immunodeficiency virus type 1 (HIV-1) isolates with nef deleted for SCID mice repopulated with human peripheral blood leukocytes (hu-PBL-SCID mice) was studied. Deletion of nef led to a substantial reduction in CD4-positive T-cell depletion and delayed kinetics of plasma viremia in infected hu-PBL-SCID mice. Deletion of the nef gene impacts both the efficiency of primary infection and the cytopathicity of virus for infected CD4-positive T cells in this animal model of HIV-1 infection.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/inmunología , Linfocitos T CD4-Positivos/fisiología , Genes nef/fisiología , VIH-1 , Leucocitos/virología , Animales , Eliminación de Gen , Humanos , Ratones , Ratones SCID , ARN Viral/análisis
13.
J Virol ; 70(6): 4184-7, 1996 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-8648765

RESUMEN

We have used envelope recombinant viruses generated between two molecular clones of human immunodeficiency virus type 1 (HIV-1), T-cell-tropic HIV-1SF2 and macrophage-tropic HIV-1SF162, to assess pathogenic potential in the human peripheral blood leukocyte-reconstituted severe combined immune deficiency mouse model. Recombinant HIV-1SF2 viruses expressing the envelope gp120 gene of HIV-ISF162 caused as rapid a CD4+ T-cell depletion as did HIV-1SF162. The reciprocal HIV-1SF162 recombinant virus with the HIV-1SF2 envelope caused slower CD4+ T-cell loss. Although changing the V3 loop sequence of HIV-1SF162 to that of HIV-1SF2 did not change the rate of CD4+ T-cell depletion, replacing the V3 of HIV-1SF2 with the sequence of HIV-1SF162 resulted in virus that was poorly infectious in vivo but not in vitro. These studies suggest that the envelope gene determines properties important for pathogenesis in vivo as well as for cell tropism in vitro. HIV-1 infection in vivo may have more stringent requirements for envelope conformation.


Asunto(s)
Linfocitos T CD4-Positivos/fisiología , Proteína gp120 de Envoltorio del VIH/genética , VIH-1/genética , Secuencia de Aminoácidos , Animales , Proteína gp120 de Envoltorio del VIH/química , VIH-1/fisiología , Humanos , Transfusión de Leucocitos , Macrófagos/virología , Ratones , Ratones SCID , Datos de Secuencia Molecular , Conformación Proteica , Replicación Viral
14.
AIDS ; 9(6): F1-6, 1995 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-7662189

RESUMEN

OBJECTIVE: Mice with severe combined immunodeficiency (SCID) transplanted with human peripheral blood lymphocytes (hu-PBL) have been shown to be useful as an animal model for HIV-1 infection. This model was used to assess the ability of a human anti-gp120 antibody to protect against HIV-1 infection. DESIGN AND METHODS: hu-PBL-SCID mice were injected with an HIV-1 broadly neutralizing human monoclonal antibody against the gp120 CD4-binding site prior to challenge with HIV-1SF2. The antibody b12, employed for these studies, was isolated from an antibody phage-display library prepared from bone-marrow of a long-term asymptomatic HIV-1-seropositive donor. Both Fab fragments and whole immunoglobulin (Ig) G1 b12 antibody were assessed for protection. RESULTS: Fab b12, tested at a dose approximately 1.9 mg/kg, was able to protect 25% of hu-PBL-SCID mice from HIV-1 infection. IgG1 b12, which displayed favorable pharmacokinetic properties, showed a dose-dependent protection that was complete with a regimen of two injections of 100 micrograms per mouse. The in vivo protective dose of antibody at the time of virus challenge was estimated to be 4.5-7 mg/kg from antibody clearance data. CONCLUSIONS: This study demonstrates for the first time that complete protection against HIV-1 infection can be achieved in the hu-PBL-SCID model by passive immunization with physiologically relevant doses of a human gp120 CD4-binding site antibody derived from natural infection.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/prevención & control , Anticuerpos Monoclonales/uso terapéutico , Antígenos CD4/inmunología , Proteína gp120 de Envoltorio del VIH/inmunología , VIH-1/inmunología , Inmunización Pasiva , Síndrome de Inmunodeficiencia Adquirida/inmunología , Animales , Anticuerpos Monoclonales/inmunología , Unión Competitiva , Relación Dosis-Respuesta Inmunológica , Humanos , Fragmentos Fab de Inmunoglobulinas/inmunología , Inmunoglobulina G/inmunología , Ratones , Ratones SCID , Pruebas de Neutralización
15.
J Immunol ; 153(10): 4826-33, 1994 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-7963548

RESUMEN

The ability to infect human peripheral blood leukocyte-reconstituted severe combined immunodeficient (hu-PBL-SCID) mice with HIV has allowed evaluation of several strategies for preventing or treating infection. In one study, hu-PBL-SCID mice derived from HIV gp160-vaccinated donors were shown to resist HIV infection, and resistance correlated best with in vitro assays of cellular immunity. We have assessed directly the importance of cellular immunity to HIV in the present experiments by the adoptive transfer of HLA-A3-restricted HIV-1 Nef-specific or HLA-B14-restricted Gag-specific CD8+ CTL clones to SCID mice bearing HLA-matched or mismatched PBL grafts. Multiple inoculations of CTL before and after HIV-1 exposure protected HLA-matched hu-PBL-SCID mice from infection, but initiation of CTL therapy on the same day as HIV infection was much less effective. However, at the high numbers of CTL required for complete protection from HIV infection, many HLA-mismatched hu-PBL-SCID mice were also protected by pre-exposure CTL transfer. Transfer of CTL with a different specificity (HTLV-1 Tax) to HLA-matched hu-PBL-SCID mice also afforded partial protection. These results suggest that HLA-restricted cytotoxicity may be less important than other nonspecific effector mechanisms for the inhibition of HIV-1 infection in vivo.


Asunto(s)
Infecciones por VIH/inmunología , VIH-1/inmunología , Linfocitos T Citotóxicos/inmunología , Animales , Secuencia de Bases , Quimera/inmunología , Pruebas Inmunológicas de Citotoxicidad , Femenino , Citometría de Flujo , Infecciones por VIH/prevención & control , Infecciones por VIH/terapia , Antígenos HLA/genética , Humanos , Inmunoterapia Adoptiva , Masculino , Ratones , Ratones SCID , Datos de Secuencia Molecular , Linfocitos T Citotóxicos/trasplante
16.
AIDS Res Hum Retroviruses ; 10(2): 131-41, 1994 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-8198867

RESUMEN

In these studies, neonatal C.B-17 severe combined immunodeficient (nSCID) mice were reconstituted with human cord blood leukocytes (hu-CBLs). The resulting hu-CBL-nSCID mice contained readily detectable human CD3+ T lymphocytes and CD20+ human B cells, and produced substantial levels of human IgM and IgG (including all subclasses). Human cells persisted in lymphoid organs and peripheral blood for at least 8 weeks, and CD4+ T cells outnumbered CD8+ T cells. Engraftment of human cells in peripheral lymphoid organs and blood was much greater than that seen in adult SCID mice grafted with adult peripheral blood leukocytes (PBLs). Hu-CBL-nSCID mice were susceptible to infection with laboratory-adapted and fresh clinical human immunodeficiency virus type 1 (HIV-1) isolates. Following infection with HIV-1, virus could be recovered by the coculture of spleen, lymph node, peritoneal cavity, liver, and plasma samples from hu-CBL-nSCID mice with fresh human peripheral blood mononuclear cells, and proviral copies were detectable following amplification using the polymerase chain reaction (PCR). HIV p24 core antigen levels in hu-CBL-nSCID mouse plasma were consistent with ongoing viral replication and high viral burdens. Rapid CD4+ T cell depletion occurred following infection with laboratory isolates of HIV-1 or a syncytium-inducing clinical isolate, but a non-syncytium-inducing clinical isolate caused expansion of CD8+ T cells, leading to an inversion of the CD4:CD8 ratio with only a transient decrease in CD4+ T cells. These results suggest that the hu-CBL-nSCID mouse system has unique features that mimic certain aspects of pediatric HIV infection, and distinguish it from other animal models of HIV infection, including the related hu-PBL-SCID model.


Asunto(s)
Infecciones por VIH/inmunología , VIH-1/inmunología , Transfusión de Leucocitos , Ratones SCID/inmunología , Animales , Animales Recién Nacidos , Linfocitos B/inmunología , Complejo CD3/inmunología , Femenino , Sangre Fetal , Enfermedad Injerto contra Huésped/inmunología , Anticuerpos Anti-VIH/inmunología , VIH-1/aislamiento & purificación , Humanos , Activación de Linfocitos , Masculino , Ratones , Subgrupos de Linfocitos T/inmunología , Linfocitos T/inmunología , Trasplante Heterólogo
17.
Science ; 260(5108): 689-92, 1993 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-8097595

RESUMEN

Human immunodeficiency virus (HIV) isolates differ in cell tropism, replication, pathogenicity, and syncytial induction in vitro. CD4+ T cells were enumerated in severe combined immunodeficient mice transplanted with human peripheral blood leukocytes (hu-PBL-SCID mice) and infected with HIV isolates with different in vitro cytopathicity. Two noncytopathic, macrophage-tropic strains, HIV-1SF162 and HIV-2UC1, induced extensive CD4+ T cell depletion, whereas HIV-1SF33, which is highly cytopathic for T cells in vitro, caused little CD4+ T cell depletion at equivalent virus burden. In vitro cytopathicity assays therefore do not predict CD4 depletion in the hu-PBL-SCID model.


Asunto(s)
Linfocitos T CD4-Positivos , Infecciones por VIH/inmunología , VIH-1/patogenicidad , VIH-2/patogenicidad , Linfopenia/inmunología , Animales , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/microbiología , Efecto Citopatogénico Viral , Infecciones por VIH/microbiología , VIH-1/fisiología , VIH-2/fisiología , Humanos , Recuento de Leucocitos , Ratones , Ratones SCID , Reacción en Cadena de la Polimerasa , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/microbiología , Replicación Viral
18.
Proc Natl Acad Sci U S A ; 90(6): 2443-7, 1993 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-8460155

RESUMEN

SCID mice reconstituted with adult human peripheral blood leukocytes (hu-PBL-SCID mice) make antigen-specific human antibody responses following secondary immunization and can be infected with human immunodeficiency virus 1 (HIV-1), suggesting that they might prove useful for evaluating protective immunity to HIV-1 following vaccination of PBL donors. HIV-seronegative volunteers were immunized with vaccinia expressing HIV-1LAV-1/Bru 160-kDa envelope glycoprotein (vaccinia gp160) and subsequently given booster injections of recombinant gp160 protein (rgp160). Their PBLs were used at intervals of 4-72 weeks after booster injections to construct hu-PBL-SCID mice, which were then challenged with 10(2)-10(3) minimal animal infectious doses of highly homologous HIV-1IIIB. Control hu-PBL-SCID mice were constructed from donors receiving vaccinia, alum, or hepatitis B vaccine. Protection against virus infection was defined as the absence of HIV-1 by culture and no detection of proviral genomes following PCR amplification. Control animals were highly susceptible to HIV infection. By contrast, hu-PBL-SCID mice reconstituted with cells from three of four donors immunized with vaccinia gp160 and recently injected with rgp160 showed no evidence of HIV-1 infection by culture or PCR assays. With increasing time after rgp160 injection, the ability of vaccine-derived hu-PBL-SCID mice to resist HIV-1 infection diminished. These results demonstrate that a potentially protective human immune response was stimulated by this HIV gp160 immunization protocol and show the utility of the hu-PBL-SCID model in the rapid evaluation of candidate vaccines.


Asunto(s)
Vacunas contra el SIDA/inmunología , Síndrome de Inmunodeficiencia Adquirida/inmunología , Productos del Gen env/inmunología , VIH-1/inmunología , Inmunoterapia Adoptiva , Leucocitos/inmunología , Precursores de Proteínas/inmunología , Linfocitos T/inmunología , Vacunas Sintéticas/inmunología , Virus Vaccinia/inmunología , Síndrome de Inmunodeficiencia Adquirida/prevención & control , Adulto , Animales , Línea Celular , Ensayo de Inmunoadsorción Enzimática , Productos del Gen env/genética , Anticuerpos Anti-VIH/sangre , Proteínas gp160 de Envoltorio del VIH , VIH-1/fisiología , Humanos , Esquemas de Inmunización , Inmunización Secundaria , Transfusión de Leucocitos , Activación de Linfocitos , Ratones , Ratones SCID , Pruebas de Neutralización , Precursores de Proteínas/genética , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/toxicidad , Vacunas Sintéticas/toxicidad , Replicación Viral
19.
J Exp Med ; 177(1): 191-4, 1993 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-8418200

RESUMEN

The autosomal recessive scid mutation results in defective immunoglobulin and T cell receptor gene rearrangement. The scid mutation occurred in the allotype congenic C.B-17 line, and up to 25% of C.B-17 scid mice spontaneously produce both T cells and immunoglobulin, a phenotype known as "leaky." Moreover, introduction of neonatal T cells into C.B-17 scid mice leads to immunoglobulin production by 100% of animals. We have produced mice homozygous for both the scid and beige mutations. By contrast with C.B-17 scid mice, BALB/c scid.beige mice have a < 2% incidence of "leakiness." This percentage does not increase with age, and introduction of neonatal T cells fails to rescue immunoglobulin production. This suggests that a gene (or genes) closely linked to the beige locus regulates B and/or T cell development.


Asunto(s)
Linfocitos B/fisiología , Homocigoto , Ratones SCID/genética , Linfocitos T/fisiología , Animales , Animales Recién Nacidos/inmunología , Genes de Inmunoglobulinas , Inmunoglobulina M/análisis , Inmunoglobulina M/biosíntesis , Ratones , Ratones Endogámicos BALB C , Mutación
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