Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies from this laboratory have demonstrated that the chemokines RANTES (recombinant human regulated upon activation, normally T cell expressed and presumably secreted), macrophage chemotactic peptide-1, recombinant human macrophage inflammatory protein-1 alpha (rhMIP-1 alpha) IL-8, and IP-10 are capable of inducing human T cell infiltration into the injection site of severe combined immunodeficiency (SCID) mice reconstituted with human PBL. However, the ability of these chemokines to facilitate T cell homing into various lymphoid tissues has not been examined. Initial studies focused on the ability of rhMIP-1 beta to induce human T cell infiltration into injection sites in human PBL-SCID mice. SCID mice received s.c. injections of rhMIP-1 beta or PBS (1 microgram/injection) in the hindflank for 4 h or sequential injections for 3 days. Biopsies of the MIP-1 beta injection site revealed the presence of significant mononuclear cell accumulation 72 h after injection. Immunohistologic evaluation determined that significant numbers of human CD3+ T cells were recruited in response to MIP-1 beta injections, and this infiltration could be specifically blocked by co-administration of anti-MIP-1 beta antiserum. We subsequently examined these chemokine-injected mice for the effect of trafficking of human T cells to peripheral lymphoid organs. Flow cytometric analysis of the thymus in human PBL-SCID mice revealed that treatment with rhMIP-1 beta or rhRANTES, but not platelet factor-4, resulted in improved thymic homing of the human T cells after 72 h. This trafficking effect was shown to be direct, as pretreatment of the human T cells with the chemokines in vitro also improved peripheral lymphoid trafficking of the human cells. In addition, co-injection of rhMIP-1 beta with anti-1 beta antiserum abrogated the increase in T cell homing to the thymus. These data demonstrate that MIP-1 beta and RANTES directly augment human T cell trafficking to peripheral murine lymphoid tissues. Chemokines may, therefore, under either isogeneic or xenogeneic conditions, play a role in normal lymphocyte recirculation and homing, and may be of potential clinical use in promoting immune cell trafficking and function.
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PMID:Chemokines and T lymphocyte activation: II. Facilitation of human T cell trafficking in severe combined immunodeficiency mice. 869 Aug 98

Age-related decline of the thymus in ICR female mice was studied following long-term (three month) weekly exposure to hydrocortisone acetate. When examined one week after cortisone injections, the well-known thymic atrophy was observed. Five weeks after 12 hydrocortisone injections, the cortical volume fraction (Vc), cortical/medullary ratio (C/M), the number of thymocytes and CD4/CD8 profiles were in the range that characterizes younger mice, compared with PBS-injected mice, uninjected controls, or mice given a single hydrocortisone injection 5 weeks earlier. It seems as if thymic involution with age was suspended during the period of glucocorticoid exposure.
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PMID:Thymic aging in ICR female mice is suspended by prolonged hydrocortisone exposure. 936 36

The reconstitution of severe combined immunodeficiency (SCID) mice with human PBL (Hu-PBL-SCID) was assessed using fresh unstimulated PBL and anti-CD3-stimulated PBL. Mice were reconstituted with PBL by intraperitoneal injection of 1-2.5 x 107 PBL in PBS; controls received PBS. Successful engraftment of human PBL in SCID mice was determined by measurement of human IgG in mouse sera, polymerase chain reaction (PCR) detection of human-specific HLA-DRbeta DNA in SCID periphery, and immunohistochemical staining of mouse tissues (spleen, lymph nodes, thymus, liver and lung) with antibodies specific for human CD45 and CD3. Human IgG was detected 1 week after reconstitution in sera of all animals that received at least 1 x 107 PBL and continued to increase for 8 weeks. Human-specific HLA-DRbeta DNA was detected in the majority of mice 3 weeks after reconstitution but not in controls. Moreover, immunohistochemical analysis of Hu-PBL-SCID mouse tissues revealed the presence of human CD45+ cells in all tissues examined. CD3+ T cell engraftment was observed in lymphoid tissues irrespective of whether PBL had been activated prior to transfer or not.
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PMID:T cell engraftment in lymphoid tissues of human peripheral blood lymphocyte reconstituted SCID mice with or without prior activation of cells. 989 29

The cytokine FLT3 ligand (FL) enhances dendritic cell (DC) generation and has therefore been proposed as a means to boost antitumor immunity. Vascular endothelial growth factor (VEGF) is produced by a large percentage of tumors and is required for development of tumor neovasculature. We previously showed that VEGF decreases DC production and function in vivo. In this study, we tested the hypothesis that VEGF regulates FL effects on DC generation. In seven experiments, four groups of mice were treated with PBS, VEGF alone (100 ng/h), FL alone (10 microgram/day), or with the combination of FL and VEGF. VEGF and PBS were administered continuously for 14 days via s.c. pumps. FL was given s.c. daily for 9 days, beginning on day 4. Tissues were collected and the number, phenotype, and function of lymph node, splenic, and thymic DCs were analyzed on day 14. As expected, treatment with FL resulted in a marked increase in the number of lymph node and spleen DCs and a smaller increase in thymic DC. Pretreatment of mice with VEGF inhibited these FL effects in lymph nodes and thymus by about 50%, whereas spleen DC numbers were undiminished by VEGF. VEGF treatment in vivo also inhibited the ability of FL to increase the number of hemopoietic precursor cells and the level of maturity exhibited by DC derived from these hemopoietic precursor cells in vitro. VEGF inhibited FL-inducible activation of transcription factor NF-kappaB. These data suggest that VEGF interferes with the ability of FL to promote dendritic cell differentiation from bone marrow progenitor cells in mice and therefore may decrease the therapeutic efficacy of FL in settings where increased numbers of DCs might provide clinical benefits.
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PMID:Effect of vascular endothelial growth factor and FLT3 ligand on dendritic cell generation in vivo. 1047 95

Thymic atrophy is a prominent feature of malnutrition. Forty-eight hours' starvation of normal mice reduced the total thymocyte count to 13% of that observed in freely fed controls, predominantly because of a diminution in the cortical CD4(+)CD8(+) thymocyte subpopulation. Prevention of the fasting-induced fall in the level of the adipocyte-derived hormone leptin by administering exogenous recombinant leptin protected mice from these starvation-induced thymic changes. The ob/ob mouse, which is unable to produce functional leptin because of a mutation in the obese gene, has impaired cellular immunity together with a marked reduction in the size and cellularity of the thymus. We found that ob/ob mice had a high level of thymocyte apoptosis resulting in a ratio of CD4(+)CD8(+) (cortical) to CD4(-)CD8(-) (precursor) thymocytes that was 4-fold lower than that observed in wild-type mice. Peripheral administration of recombinant leptin to ob/ob mice reduced thymocyte apoptosis and substantially increased both thymic cellularity and the CD4(+)CD8(+)/CD4(-)CD8(-) ratio. In contrast, a comparable weight loss in pair-fed PBS-treated ob/ob mice had no impact on thymocyte number. In vitro, leptin protected thymocytes from dexamethasone-induced apoptosis. These data indicate that reduced circulating leptin concentrations are pivotal in the pathogenesis of starvation-induced lymphoid atrophy.
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PMID:Leptin protects mice from starvation-induced lymphoid atrophy and increases thymic cellularity in ob/ob mice. 1052 43

The objective of this study was to determine whether recombinant plasmid DNA injected intramuscularly into chickens expressed the gene of interest in vivo and could be subsequently detected in primary and secondary lymphoid tissues with polymerase chain reaction (PCR). The VP2 capsid protein gene of the standard challenge strain (STC) of infectious bursal disease virus (IBDV) was cloned into a eukaryotic plasmid, and purified DNA was prepared. Fourteen 2-wk-old chickens were injected in the pectoral musculature with 500 microg of plasmid DNA dissolved in sterile PBS. Seven chickens were similarly injected with PBS alone. Pectoral muscle, thymus, spleen, bursa of Fabricius, and cecal tonsils were collected at 12, 24, 36, 48, 72, 96, and 168 h postinjection for detection of protein expression (in muscle) and to extract total DNA for PCR amplification of the VP2 capsid gene. Expression of VP2 was demonstrated in muscle tissue at 12 and 24 h postinjection by using an indirect immunofluorescence assay. PCR amplification with primers specific for the VP2 gene showed that the DNA was present in the thymus, spleen, and bursa of Fabricius but not in cecal tonsils. These results demonstrate that plasmid DNA injected directly into the pectoral muscle of chickens is transcribed and translated at the injection site and promptly distributed to primary and secondary lymphoid tissues.
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PMID:Fate of plasmid DNA encoding infectious bursal disease virus VP2 capsid protein gene after injection into the pectoralis muscle of the chicken. 1187 29

Methylene blue (MB), riboflavin (RB) and psoralen sensitizers (4' aminomethyl-4,5',8-trimethylpsoralen [AMT] and derivatives) are under study as sensitizers of viral inactivation of blood products such as plasma proteins, platelets and red cells, all of which lack genomic nucleic acid. To predict where these sensitizers accumulate in viruses and in cells, their relative affinities for calf thymus DNA, neutral and negatively charged phospholipids and albumin were determined by dialysis. MB has a strong affinity for nucleic acid and negatively charged phospholipid, but little affinity for albumin or neutral phospholipid. RB has modest affinity for nucleic acid and little affinity for albumin or either phospholipid. AMT has substantial affinity for nucleic acid, neutral and negatively charged phospholipids and albumin. Neither AMT nor RB binds to poly G, although MB has some affinity for this polymer. Evidence of association of RB with guanosine monophosphate, adenosine monophosphate and tryptophan methylester hydrochloride in PBS buffer in the presence and absence of formamide was obtained from nonlinear Stern-Volmer plots and shifts in the ground state absorption spectrum of RB.
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PMID:Binding affinities of commonly employed sensitizers of viral inactivation. 1208 15

Survivin is the smallest member of mammalian IAP (inhibitor of apoptosis) family. It is ubiquitous during embryonic development but is not expressed in normal post-natal tissues, except the thymus, colonic epithelial cells and CD34+ hematopoietic stem cells. However, its expression is upregulated during neoplastic transformation in both solid organ and hematological malignancies, including leukemia and lymphoma. In this study, we used RNA interference with short hairpin RNA (shRNA) technique to inhibit survivin expression in a Burkitt's lymphoma cell line Raji and validated its effects on apoptosis and cell proliferation. A survivin-shRNA expression vector were constructed and introduced into Raji cells. Expression of survivin mRNA and protein was assessed by RT-PCR and western blot analysis. Apoptosis index of transfected cells was quantified by flow cytometry and cell proliferation was enumerated by trypan blue exclusion. In Raji cells treated with survivin-shRNA expression vector, survivin mRNA levels were significantly reduced by 67.14% (transient transfection) and 64.28% (stable transfection) respectively, compared with control-shRNA treated group and PBS treated group (p<0.05). The levels of survivin protein were significantly reduced by 62.50% (transient transfection) and 60.93% (stable transfection), compared with the two control groups (p<0.05). Apoptosis index was significantly increased during transient transfection and stable transfection, respectively 31.20+/-2.45% and 29.40+/-1.72% (p<0.05). Survivin-shRNA inhibited the proliferation of Raji cells of stable transfection. In conclusion, the vector-based survivin-shRNA can effectively reduce the expression of survivin gene and induce apoptosis and growth inhibition of transfected Raji cells. We suggest that survivin can be regarded as an ideal target for new anticancer intervention of NHL.
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PMID:Knockdown of survivin gene by vector-based short hairpin RNA technique induces apoptosis and growth inhibition in Burkitt's lymphoma Raji cell line. 1665 89

A DNase from Bacillus subtilis which specifically hydrolyzes native DNA of phage PBS 1 has been purified and characterized. The mode of action of the enzyme is endonucleolytic, yielding deoxyuridine and oliogonucleotides of various sizes. The primary site of enzymatic attack is deoxyuridylic acid in the DNA. A mild nitrous acid treatment of thymine-containing thymus DNA, which deaminates 30% of the cytosine residues, renders the DNA susceptible to the DNase. Nicked DNA from coli phage T5 and hydroxymethyluracil-containing DNA from phage PBS 15 are not sensitive to this DNase.
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PMID:DNase Specific for Uracil-Containing Bacteriophage DNA. 1678 46

The production of fully immunologically competent humanized mice engrafted with peripheral lymphocyte populations provides a model for in vivo testing of new vaccines, the durability of immunological memory and cancer therapies. This approach is limited, however, by the failure to efficiently engraft human B lymphocytes in immunodeficient mice. We hypothesized that this deficiency was due to the failure of the murine microenvironment to support human B cell survival. We report that while the human B lymphocyte survival factor, B lymphocyte stimulator (BLyS/BAFF) enhances the survival of human B cells ex vivo, murine BLyS has no such protective effect. Although human B cells bound both human and murine BLyS, nuclear accumulation of NF-kappaB p52, an indication of the induction of a protective anti-apoptotic response, following stimulation with human BLyS was more robust than that induced with murine BLyS suggesting a fundamental disparity in BLyS receptor signaling. Efficient engraftment of both human B and T lymphocytes in NOD rag1(-/-) Prf1(-/-) immunodeficient mice treated with recombinant human BLyS is observed after adoptive transfer of human PBL relative to PBS treated controls. Human BLyS treated recipients had on average 40-fold higher levels of serum Ig than controls and mounted a de novo antibody response to the thymus-independent antigens in pneumovax vaccine. The data indicate that production of fully immunologically competent humanized mice from PBL can be markedly facilitated by providing human BLyS.
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PMID:Human BLyS facilitates engraftment of human PBL derived B cells in immunodeficient mice. 1878 35


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