Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.2.1.23 (beta-galactosidase)
14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Specific immune responses of inbred miniature pigs following vaccination and challenge with suid herpesvirus 1 (SHV-1) were determined. Vaccination of swine with SHV-1 elicited both specific neutralizing antibody and lymphoproliferative responses. Moreover, pigs vaccinated with SHV-1 were fully protected against a lethal virus challenge. Pigs vaccinated with a recombinant (r) SHV-1 virus, followed by challenge with a virulent SHV-1, had lower percentages of circulating T- and B-lymphocytes, and showed a significant (P < or = 0.05) reduction in peripheral blood mononuclear cell (PBMC) antibody-dependent cell-cytotoxicity than control (noninfected, SHV-1 sero-negative) animals. From the 5th through the 8th week of postchallenge, rSHV-1 was isolated from 2 of 4 pigs. Presence of r-virus was indicative that PBMC were infectious in vivo. The rSHV-1, with beta-galactosidase activity, was only recovered from ConA- and IL-2-stimulated primary PBMC cocultivated with porcine kidney cells. Control pigs exposed to challenge SHV-1 elicited both specific neutralizing antibody and lympho-proliferative responses followed by subsequent infection. These infected pigs, compared to control pigs, had significantly (P < or = 0.05) lowered percentages of T- and B-lymphocytes, lowered T-cell mitogenic responses, variable PBMC counts, and lowered blood phagocytic cell function. When PBMC from control pigs were cultured and infected with SHV-1, the virus caused a significant (P < or = 0.05) suppression of T-cell proliferation and PBMC mitochondrial dehydrogenase and macrophage activities.
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PMID:Study of immune function in inbred miniature pigs vaccinated and challenged with suid herpesvirus 1. 854 90

The role of the medullary thymic epithelial cells in tolerance induction to MHC class I restricted self peptides has been analyzed by studying the beta-galactosidase (beta-gal)-specific cytotoxic T cell response of a transgenic mouse expressing beta-gal in the thymus, skin, and central nervous system (Tg beta-gal mouse). Our results showed that: 1) beta-gal expression in the thymus was limited in a subpopulation of medullary epithelial cells, and bone marrow-derived thymic cells were beta-gal-1; 2) Tg beta-gal mice did not mount an anti-beta-gal CTL response even in the presence of exogenous IL-2, while Tg beta-gal-->B6 chimeras responded to beta-gal as strongly as NTg beta-gal mice; 3) Tg beta-gal mice did not generate CTL against the immunodominant Kb-restricted beta-gal 497-504 peptide; 4) tolerance was due to the thymic epithelial cells that expressed beta-gal because nude mice grafted with thymus from Tg beta-gal mice were also unable to respond to beta-gal; 5) the Tg beta-gal mouse-derived beta-gal+ medullary epithelial TEC.X10 line presented the Kb-restricted beta-gal 497-504 epitope. In conclusion, these results demonstrate that medullary thymic epithelial cells induce a complete tolerance towards class I-restricted self peptides presented on their own surface.
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PMID:Medullary thymic epithelial cells induce tolerance to intracellular proteins. 855 24

Recombinant adenovirus (rAd), deleted of critical genes that enable viral replication and replaced with genes encoding heterologous proteins, has been shown to be a safe and effective vector in gene therapy studies. To evaluate a potential role for rAd as an immunogen, we used two different replication-defective type 2 rAds encoding the model Ag, beta-galactosidase (beta-gal). To determine whether rAd elicited the kind of immune responses therapeutic in an anti-tumor setting, the beta-gal-expressing adenocarcinoma, CT26.CL25, was used. Splenocytes from BALB/c mice immunized with 1 x 10(7) infectious units (iu) of rAd demonstrated anti-beta-gal activity after in vitro culture with the relevant L(d) beta-gal peptide. Adoptive transfer of these same splenocytes produced dramatic regression of established pulmonary metastases. However, when tumor-bearing mice were treated with 1 x 10(7) iu of rAd, no reduction in established disease was observed even when rAd was given with exogenous IL-2. To increase the viral dose delivered to each animal, we used an E1-E4-deleted rAd that could be grown to much higher titers. Significant reduction occurred with 10-fold more rAd (1 x10(8) iu) was administered. Exogenous IL-2 administration with 1 x 10(8) iu of rAd resulted in augmentation of this anti-tumor effect. These findings demonstrate that when using a nonreplicating virus, the viral dose is directly related to the immune response generated. These data constitute the first reported use of rAd in the treatment of an established experimental cancer and may have implication for the treatment of human cancer.
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PMID:Therapeutic antitumor response after immunization with a recombinant adenovirus encoding a model tumor-associated antigen. 859 66

The immunogenic properties of a replication-defective herpes simplex virus HD-2, containing the Escherichia coli lacZ gene under control of the HSV ICP8 early gene promoter were studied in BALB/c mice. Experiments were designed to determine if the HD-2 virus preferentially stimulated either Th1- or Th2-associated immune responses to beta-galactosidase (beta gal). Sera from mice immunized i.p. or s.c. with virus HD-2, beta gal on aluminum phosphate adjuvant, or a control ICP8 deletion mutant, d301, were assayed for total and Ag-specific IgG1 and IgG2a Abs, beta gal-driven lymphocyte proliferation, and in vitro production of the cytokines IFN-gamma, IL-4, and IL-2. Viruses HD-2 and d301 preferentially stimulated the production of total serum IgG2a following two immunizations i.p. or a single immunization s.c., while only HD-2 virus stimulated in vivo production of beta gal-specific IgG2a serum Abs. In contrast, beta gal adsorbed on AIPO4 preferentially stimulated production of Ag-specific IgG1 serum Abs. The HD-2 virus also induced a potent cellular proliferative response to beta gal, which was still pronounced 5 wk after primary immunization. Cultured lymphocytes from HD-2-immunized mice produced IFN-gamma after 5 days in culture with soluble beta gal in an Ag- and dose-dependent fashion. These results demonstrate that replication-defective mutants of HSV can be used as vectors for eliciting Th1-associated immune responses to a heterologous Ag expressed from the viral genome.
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PMID:Th1-associated immune responses to beta-galactosidase expressed by a replication-defective herpes simplex virus. 875 44

The p40 subunit of interleukin 12 (IL-12p40) has been known to act as an IL-12 antagonist in vitro. We here describe the immunosuppressive effect of IL-12p40 in vivo. A murine myoblast cell line, C2C12, was transduced with retro-virus vectors carrying the lacZ gene as a marker and the IL-12p40 gene. IL-12p40 secreted from the transfectant inhibited the IL-12-induced interferon gamma (IFN-gamma) production by splenocytes in vitro. Survival of C2C12 transplanted into allogeneic recipients was substantially prolonged when transduced with IL-12p40. Cytokine (IL-2 and IFN-gamma) production and cytotoxic T lymphocyte induction against allogeneic C2C12 were impaired in the recipients transplanted with the IL-12p40 transfectant. Delayed-type hypersensitivity response against C2C12 was also diminished in the IL-12p40 recipients. Furthermore, serum antibodies against beta-galactosidase of the T-helper 1-dependent isotypes (IgG2 and IgG3) were decreased in the IL-12p40 recipients. These results indicate that locally produced IL-12p40 exerts a potent immunosuppressive effect on T-helper 1-mediated immune responses that lead to allograft rejection. Therefore, IL-12p40 gene transduction would be useful for preventing the rejection of allografts and genetically modified own cells that are transduced with potentially antigenic molecules in gene therapy.
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PMID:Local production of the p40 subunit of interleukin 12 suppresses T-helper 1-mediated immune responses and prevents allogeneic myoblast rejection. 879 58

Correlations between the in vitro biological properties of HIV strains isolated from patients and the prognosis of their disease have been reported. We developed a technique to study the phenotype of HIV strains isolated from patients. We used the P4 cell line, derived from HeLa cells, which has been transfected with receptor CD4 gene. HIV laboratory strain (HIVLAI) and peripheral blood leukocytes (PBLs) from donors infected with HIVLAI induce syncytium in P4 cell cultures in vitro. The presence of reporter gene (LacZ gene) under the control of the HIV-1 long terminal repeat (LTR) in these cells allows colorimetric visualization of syncytia in the cytoplasm using a beta-galactosidase (beta gal) assay in the presence of X-gal. We cocultivated 1 x 10(6) patient PBLs with 2 x 10(6) normal PHA-activated normal PBLs for 4 days in the presence of IL-2 in 24-well plates. Half of the medium was replaced twice a week and PHA-activated normal PBLs were added every 7 days. HIV-1 was isolated from cocultured PBLs of 18 patients with advanced-stage HIV infection as assessed by the production of HIV p24 detected with a commercially available HIV-1 p24 ELISA. Supernatant and 10(5) cells were collected twice a week from cocultured PBLs and were added to P4 cells in 96-well microtiter plates. The cultures were observed every day for 3 days and then the beta gal assay was performed. We did not observe any effect with cells and supernatant from 8 patients, harvested from cultures incubated for as long as 28 days. The phenotype of these isolates was called NC (noncytopathic). In cells from 2 patients, we obtained blue multinucleated giant cells; the phenotype of these strains was called SI (syncytium inducing). In cultures from 8 other patients, we obtained the death of P4 cells without syncytium formation, and the phenotype of these strains was called CI (cell-killing inducing). In every case, the cytopathic effect of HIV-1 isolates could be detected with cocultured PBLs collected as early as day 4 of culture. Cocultured PBLs from 13 healthy controls did not alter the P4 cells. We displayed the replication of CI strains of HIV-1, but not the one of NC strains in P4 cell line. Our micromethod allowed the detection of cytopathic effects of HIV isolates. Further investigations should define the clinical applications of this method.
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PMID:A microassay for determination of the cytopathogenicity of human immunodeficiency virus type-1 isolates. 880 3

The efficacy of gene therapy for glioma was examined using adeno-associated virus (AAV)-based vectors to deliver genes to experimental tumors in mice. Stereotactic injection of 2 x 10(5) U-251SP human glioma cells into the brains of nude mice produced tumors of 19.06 +/- 1.79 mm2 17 days after injection. Employing a high titer preparation of AAV vector containing the gene for beta-galactosidase (AAV-lacZ), dose-dependent transduction of U-251SP cells was seen in vitro. When 1.6 x 10(10) AAV-lacZ particles were directly injected into tumors in vivo, 30-40% of the cells along the needle track expressed beta-galactosidase. Transduction of U-251SP cells in vitro with an AAV vector containing a bicistronic gene encoding both herpes simplex thymidine kinase and human interleukin-2 (AAV-tk-IRES-IL2) rendered them sensitive to the cytocidal effects of ganciclovir (GCV) and IL-2 was produced in a dose-dependent manner. Cocultures of AAV-tk-IRES-IL2 transduced cells and nontransduced cells proved highly sensitive to GCV indicating the contribution of the bystander effect. Stereotactic delivery of 6 x 10(10) AAV-tk-IRES-IL2 particles into day 7 tumors in nude mice followed by administration of GCV for 6 days, resulted in a 35-fold reduction in the mean volume of tumors compared with controls. Normal brains did not suffer from any toxic effect of the administration of AAV-tk-IRES-IL2 and GCV. These results indicate that high titer AAV vector treatment may be safe and effective for in vivo gene therapy of human brain tumors.
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PMID:Gene therapy against an experimental glioma using adeno-associated virus vectors. 894 Jun 35

Dendritic cells (DCs) are the most potent antigen-presenting cells (APCs) for the initiation of antigen-specific T-cell activation. DCs may be highly enriched from peripheral blood-adherent leukocytes by short-term (7-day) culture in the presence of interleukin (IL)-4 and granulocyte-macrophage colony-stimulating factor. Various methods of gene transfer were studied, including DNA/liposome complexes, electroporation, CaPO4 precipitation, and recombinant adenovirus (AdV) vectors. Low levels of expression were obtained with the physical methods tested. In contrast, AdV vectors expressing luciferase, beta-galactosidase, IL-2, and IL-7 all readily transduced human DCs. Increasing levels of gene expression were observed over a range of multiplicity of infection (MOI) of 10:1 to 10,000:1, with transduction efficiencies exceeding 95% at higher MOI. Although levels of maximal gene expression in DCs were significantly lower than those obtained using human tumor cell lines, IL-2 and IL-7 production of up to 5 x 10(2) ng/10(6) DC were achieved. These results suggest that AdV vectors are a promising vehicle for genetically engineering human DCs.
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PMID:A comparison of gene transfer methods in human dendritic cells. 901 47

Replication-deficient adenovirus (Ad) vectors are effective to specifically target the respiratory epithelium for either corrective gene therapy such as cystic fibrosis or for mucosal immunization. As a consequence of transducing the lower respiratory tract with an E1/E3 deleted Ad5 vector, host responses have been characterized by the duration of transgene expression and by the induction of CTL responses. However, limited emphasis has been devoted to understanding the contribution of CD4+ T cell responses to the Ad vector. Both CD4+ and CD8+ T cells migrate into the lung following sequential intratracheal Ad5 transgene instillations. Isolated CD3+ T lymphocytes from the lungs were predominantly of the Th2 type, and after cell sorting, the IL-4-producing T cells were largely CD4+, while IFN-gamma expression was associated with both CD4+ and CD8+ T cells. Ab responses to the Ad5 vector and to the expressed transgene beta-galactosidase (beta gal) revealed elevated bronchial and serum IgA and IgG Abs with low neutralization titers. Analysis of serum IgG subclass responses showed IgG1 and IgG2b with lower IgG2a Abs to Ad5 and IgG2a and IgG2b Ab responses to beta gal. Ad5-specifc CD4+ T cells produced both Th1 (IFN-gamma and IL-2)- and Th2 (IL-4, IL-5, IL-6)-type cytokines, while beta gal-specific CD4+ T cells secreted IFN-gamma and IL-6. This study provides direct evidence for the concomitant induction of Th2- with Th1-type responses in both the pulmonary systemic and mucosal immune compartments to the Ad5 vector as well as a Th1-dominant response to the transgene.
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PMID:Adenoviral gene delivery elicits distinct pulmonary-associated T helper cell responses to the vector and to its transgene. 921 83

We have evaluated the feasibility of gene transduction using replication-defective adenovirus vector as a novel therapy for medullary thyroid carcinoma (MTC), a thyroid C cell neoplasm. Replication-defective adenoviruses were constructed to express murine interleukin-2 (mIL-2) gene and Escherichia coli beta-galactosidase (beta-gal; lacZ) gene under the control of the human cytomegalovirus (CMV) promoter (AdCMVmIL2, AdCMVbeta-gal) by homologous recombination. The efficiency of transduction was evaluated using AdCMVbeta-gal at different conditions. The gene transduction efficiency was dependent on multiplicity of infection, duration of exposure to the virus, and viral concentration. The expression of functional mIL-2 in transduced tumor cells was verified both in vitro and in vivo. Two cell lines (rat MTC and mMTC) secreted large amounts of functional mIL-2 after transduction, as tested in cytotoxic T lymphocyte (CTL) L-2 cells. When AdCMVmIL2-infected mMTC cells were injected s.c. into their host animals, tumors developed in 2 of 10 animals, in contrast to 9 of 10 animals injected with AdCMVbeta-gal-infected mMTC cells and all 10 animals injected with parental mMTC cells. Moreover protected animals developed a long lasting immunity against mMTC tumor cells and their splenocytes, showing cytotoxicity to parental tumor cells, and active natural killer (NK) cell activity. BALB/c-SCID (severe combined immune deficiency) mice were also used to evaluate the function of NK cells in antitumor activities. No tumor developed in SCID mice injected with AdCMVmIL2-infected cells, whereas all animals injected with either AdCMVbeta-gal-infected or parental mMTC cells developed tumors. Our data indicate that IL-2 production by MTC cells leads to rejection in syngeneic animals and suggest that both cytotoxic T cells and NK cells may play an important role. In addition, transduction of adenoviral vectors into tumor cells produces some nonspecific antitumor effects.
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PMID:Immunotherapy for medullary thyroid carcinoma by a replication-defective adenovirus transducing murine interleukin-2. 944 31


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