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:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Conjunctival lymphoid follicles (CLFs), present in normal individuals, undergo hyperplasia upon conjunctival infection by a specific array of pathogens; infection-associated enlargement of draining preauricular lymph nodes suggests that conjunctival follicles participate in the afferent limb of acquired immune responses for the ocular surface. The present study was performed to delineate the structural and lymphoid anatomy of CLFs in the baboon (Papio anubis), a non-human primate conjunctival model with close similarity to the human. Conjunctiva from both eyes, along with mesenteric lymph node, spleen, tonsil, and ileum controls were harvested from ten baboons at necropsy, and studied by histochemical and immunohistochemical methods. Baboon conjunctival follicles were identified as dense oval collections of leukocytes in the substantia propria with infiltration into a thinned overlying conjunctival epithelium. Goblet cells were universally absent, the overlying mucin layer was attenuated, and the follicle-associated epithelium (FAE) demonstrated comparatively diminished alkaline phosphatase expression. The basement membrane overlying each follicle appeared discontinuous. CD4-positive T lymphocytes were distributed in parafollicular areas and to a lesser degree in follicle germinal centers. B lymphocytes formed the predominant cell in follicles, and also heavily infiltrated the FAE. B cell IgM expression was prominent in germinal centers, while IgD staining occurred in a horseshoe-shaped distribution in the follicle mantle zone. Although B cell IgA expression was noted in the non-follicular conjunctiva, IgA expression was inconspicuous within conjunctival follicles. S-100- and CD1a-positive dendritic cells were found in FAE, while fascin-positive mature dendritic cells appeared in the deeper areas of each follicle. CD68-positive macrophages were dispersed throughout the follicles. CD35-positive follicular dendritic cells were observed only in germinal centers. CLFs appear highly organized consistent with a role in the adaptive immune response to conjunctival pathogens.
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PMID:Structural and cellular architecture of conjunctival lymphoid follicles in the baboon (Papio anubis). 1274 51

CCR5-using (R5) human immunodeficiency virus type 1 (HIV-1) is a major viral population that is transmitted by sexual intercourse and that replicates in infected individuals during the asymptomatic stage of HIV-1 infection, suggesting that agents effective against R5 HIV-1 can be expected to prevent viral transmission and delay disease progression. However, R5 HIV-1 is unable to replicate in human T-cell lines, which is an apparent obstacle to efficient and reliable susceptibility tests of compounds for their activities against R5 HIV-1. To establish a simple and rapid assay system for the monitoring of R5 HIV-1 replication and drug susceptibility, we have established a novel reporter T-cell line, MOCHA (which represents MOLT-4 cells stably expressing CCR5 and carrying the HIV-1 long terminal repeat-driven secretory alkaline phosphatase). Cells of this cell line express CD4, CXCR4, and CCR5 on their surfaces and secrete human placental alkaline phosphatase into the culture supernatants during HIV-1 infection. MOCHA cells proved to be highly permissive for the replication of R5 HIV-1 as well as CXCR4-using (X4) HIV-1, and the alkaline phosphatase activity increased in parallel with increasing HIV-1 p24 antigen levels in the culture supernatants. When HIV-1 reverse transcriptase inhibitors, protease inhibitors, and entry inhibitors, including the CCR5 antagonist TAK-779 and the CXCR4 antagonist AMD3100, were examined for their inhibitory effects on R5 and X4 HIV-1 replication in MOCHA cells, the antiviral activities of these compounds were found to be almost identical to those previously reported in peripheral blood mononuclear cells. Thus, MOCHA cells are an extremely useful tool for detection of R5 and X4 HIV-1 replication and drug susceptibility tests.
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PMID:Novel reporter T-cell line highly susceptible to both CCR5- and CXCR4-using human immunodeficiency virus type 1 and its application to drug susceptibility tests. 1279 75

The lymphocyte-osteoclast interaction has recently been described. The aim of this study was to investigate the possible relationship between ankylosing spondylitis (AS) and bone metabolism. Bone metabolism was evaluated in the blood of 49 patients with AS by means of biochemical markers and bone mineral density (BMD) with a Lunar device. Bone formation markers, bone specific alkaline phosphatase (BALP), osteocalcin (BGP), bone resorption markers, pyridinoline (Pyd), deoxypyridinoline (Dpyd) and lymphocyte surface markers (CD3, CD19, CD4, CD8, CD16+56) were analysed with ELISA and flow-cytometry methods. The patients had significantly lower femoral neck and trochanter BMD than the controls. Dpyd concentrations were negatively correlated to CD3+% and CD3-/CD16+56% cells. Neither mineral nor hormone levels were significantly correlated with absolute T scores of BMD of the hip sites. BALP and BGP were negatively correlated to BMD when expressed as T scores. We conclude that AS is related to accelerated osteoclastic activity. Many lymphokines and growth factors produced by lymphocytes can influence osteoclastogenesis and probably play a role in rheumatologic/inflammatory disorders.
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PMID:Association of immune function with bone mineral density and biochemical markers of bone turnover in patients with anklylosing spondylitis. 1462 78

Peripheral T-cell lymphoma (PTCL) is a group of diseases which are common in Asia and areas of South and Central America. They are highly associated with the Epstein-Barr virus (EBV) infection. In the present study the authors evaluated patients with gastrointestinal involvement of PTCL with respect to clinical findings and outcome, pathologic features, and molecular analysis for EBV infection and the clonality of tumor cells. From January 1997 through December 2000, 7 patients with gastrointestinal tract involvement of PTCL were identified. The frequency of gastrointestinal tract involvement in the various types of PTCL was 5.4 per cent (7 of 129 cases). The pertinent clinical features were prolonged fever, weight loss, anemia, hepatosplenomegaly, lymphadenopathy, multiorgan involvement, and gastrointestinal bleeding. Laboratory results showed a significantly high serum level of alkaline phosphatase and lactate dehydrogenase, and abnormal coagulograms. Five patients died within 4 months after onset of illness, while two were in complete remission after chemotherapy. The tumor cell morphology was classified into three categories: small-sized cells, mixed medium- and large-sized cells, and large-sized cells. The antigenic phenotypes of the tumor cells were LCA+, CD3+, CD15-, CD16-, CD30-, CD45R0+, CD57-, CD68-, EMA-, betaF1-, granzyme B+, TIA-1+, and p53+. The expression of CD4, CD8, CD56 and CD20 was variable. EBV-RNA expression by in situ hybridization (EBER-ISH) study was positive and T-cell receptor (TCR) beta and/or gamma gene rearrangements were detected in all patients. DNA sequence analysis showed high identity to the human TCR germline gene. PTCL with gastrointestinal tract involvement was associated with EBV infection. The tumor cells were mature T cells with some NK-cell antigenic expression and all demonstrated TCR gene rearrangements.
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PMID:Epstein-Barr virus-associated peripheral T-cell lymphoma with gastrointestinal tract involvement. 1464 66

Muscle-based gene therapy and tissue engineering hold great promise for improving bone healing. However, the relative advantage of muscle-derived stem cells (MDSCs) or primary muscle-derived cells (MDCs) remains to be defined. We compared the ability of MDSCs and different subpopulations of MDCs (PP1 and PP3) to induce bone formation via ex vivo gene therapy. We were able to efficiently transduce the MDSCs and all the other evaluated populations of MDCs (efficiency of transduction = approximately 80%) by using a retroviral vector expressing human bone morphogenetic protein 4 (BMP4). All the transduced cell populations secreted high levels of BMP4 (140-300 ng/10(6) cells/24 h), but the MDSCs differentiated toward the osteogenic lineage more effectively than did the other muscle cell populations, as indicated by the expression of alkaline phosphatase, an early osteogenic marker. von Kossa staining indicated that mineralized bone formed as early as 7 days after implantation of any of the BMP4-expressing cell populations into immunocompetent syngeneic mice; however, MDSCs expressing BMP4 produced significantly more bone than did the other MDC populations, as evidenced by both histomorphometry and biochemical analysis. Further investigation revealed that MDSCs expressing BMP4 persisted for a significantly longer period of time at the bone forming sites than did the other BMP4-expressing MDC populations. Additionally, MDSCs expressing BMP4 triggered a smaller infiltration of CD4 lymphocytes within the bone forming areas than did the other MDC populations expressing BMP4. Finally, we demonstrated that MDSCs expressing BMP4 can heal a critical-sized skull bone defect in immunocompetent mice. In summary, this study shows that MDSCs are better than primary MDCs for use as cellular vehicles in BMP4-based ex vivo gene therapy to improve bone healing. The advantage of MDSCs may be attributable, at least in part, to their lower immunogenicity and higher capacity for in vivo survival.
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PMID:Ex vivo gene therapy-induced endochondral bone formation: comparison of muscle-derived stem cells and different subpopulations of primary muscle-derived cells. 1519 44

Seventy patients with various types of peripheral T-cell proliferative disease/lymphoma who manifested with prolonged fever, weight loss, anemia, lymphadenopathy, hepatosplenomegaly and elevated serum levels of alkaline phosphatase and/or lactate dehydrogenase were evaluated. Histopathological examination of the livers revealed T-cell infiltration into the hepatic sinusoids and portal tracts. The morphology of the infiltrated T cells varied from mature small lymphocytes to malignant lymphoid cells. The liver pathology was classified into four groups on the basis of cellular atypia. Group A and group B showed mature lymphoid cell infiltration; however, only group B had multiple large areas of hepatocellular necrosis. Group C showed atypical lymphoid cell infiltration and in group D malignant lymphoid cell infiltrates were demonstrated. The majority of the antigenic phenotypes of these T-cell infiltrates were CD3+, CD4-, CD8+, CD20-, CD45RO+, CD56-, CD57-, TIA-1+ and betaF1-. Epstein-Barr virus RNA in the nuclei of the infiltrated T cells was recorded in 38.6% of the patients and was more common in groups C and D. Patients in groups B, C and D had a very poor prognosis, median survival was only 1 month, whereas median survival in group A patients was 36 months. Chemotherapy was not effective in improving survival. Monoclonal band/s of T-cell receptors (TCR) beta and/or gamma gene rearrangements were detected in 88.6% of patients, and DNA-sequence analysis showed high identity to the human TCR germline gene.
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PMID:Hepatic cytotoxic T-cell infiltrates in patients with peripheral T-cell proliferative diseases/lymphomas: clinicopathological and molecular analysis. 1553 24

This retrospective and longitudinal study evaluated the long-term hepatic tolerance of a nelfinavir (NFV)-antiretroviral combined regimen in 82 patients of the HCV-HIV Cohort of CISIH-Sud of Marseilles. Follow-up data (liver enzyme levels, CD4 cell count, HIV viral load, and metabolic parameters) of patients treated with NFV on inclusion or during the follow-up of the cohort were analyzed under treatment over 24 months. Comparisons were performed with X2 or Kruskal-Wallis tests. At baseline (n = 82), the median exposure to NFV was 4.1 months; 58 patients received NFV combined with NRTI and 24 with NNRTI. The median CD4 cell count was 337/mm3 [interquartile range (IR): 216-480) and 39.7% had an undetectable HIV RNA level. Qualitative HCV PCR was positive in 91% of the patients and 19/51 patients with liver biopsy were F3-F4. Median alanine and aspartate aminotransferase (ALAT, ASAT), gamma-glutamyltransferase (GT), and alkaline phosphatase (ALP) were 46 UI/liter (IR: 36-76), 55 UI/liter (IR: 32-97), 97 UI/liter (IR: 50-194), and 88 UI/liter (IR: 72-104), respectively, with 76% of the patients with ALAT/ASAT grade <2. Median follow-up was 23 months (IR: 13.8-37). No significant difference was observed in the distribution of ALAT, ASAT, GT, and ALP as well as of ALAT/ASAT grades over the 24-month study period. Patients treated with NFV + NNRTI had significantly higher GT and ALP levels at baseline with no significant increase during follow-up. Cholesterol, triglyceride, and glycemia distributions remained stable over time. In conclusion, this study showed a good hepatic and metabolic tolerance of a long-term NFV-combined regimen in HIV-HCV coinfected patients.
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PMID:Nelfinavir in HIV-HCV coinfected patients: a 24-month follow-up in a cohort of 82 patients. 1622 10

Bone loss is a typical pathological feature of chronic inflammatory bone diseases including rheumatoid arthritis, in which CD4 effector T cells play critical roles. We found that activated mouse Th2 and not Th1 cells produced the parathyroid hormone (PTH). Unlike in the parathyroid cells, PTH expression in Th2 cells was not regulated by the fluctuation of calcium level, but rather it required the full activation of the T cells. Although PTH was expressed in immature Th2 cells, and its receptor was transiently expressed during Th1 and Th2 cell differentiation, PTH did not significantly affect the outcome of the differentiation. In primary osteoblasts cultured in Th2 cell condition medium, the alkaline phosphatase (ALP) activity was maintained at a basal level. However, antagonizing PTH in the condition medium resulted in a significant reduction of the ALP activity. These results demonstrated an important role of the Th2 cell-derived PTH in maintaining the bone-forming activity of the osteoblasts under inflammatory conditions. In osteoblasts cultured in the Th1 cell condition medium, the ALP activity was significantly suppressed. Neutralizing IFN-gamma alleviated the suppression. Conversely, treatment of osteoblasts with IFN-gamma suppressed the ALP activity. Unlike ALP, expression of the major bone matrix proteins by the osteoblasts was only minimally affected by either Th1 or Th2 cytokine environment. In addition, the Th2 cytokine environment also regulated to expression of receptor activator of NF-kappaB ligand and osteoprotegerin through both PTH-dependent and -independent mechanisms. Our study therefore identified new regulatory events in bone remodeling under inflammatory conditions.
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PMID:Differential regulation of osteoblast activity by Th cell subsets mediated by parathyroid hormone and IFN-gamma. 1633 69

Human leukocyte antigen-G (HLA-G) displays immunotolerogenic properties toward effector cells in graft rejection through inhibition of natural killer (NK) and cytotoxic T lymphocyte (CTL)-mediated cytolysis and CD4+ T-cell alloproliferation. CD4(+)CD25(+)high regulatory T (Treg) cells are pivotal for the maintenance of self-tolerance of pathogenic alloresponses after solid organ or bone marrow transplantation in murine model systems. The aim of this study was to investigate whether there was an association between soluble and membrane-bound HLA-G levels on Treg cells and liver graft prognosis. For this purpose, we studied 37 liver transplant patients and 13 healthy blood donors. To investigate the expression of HLA-G on the surface of peripheral mononuclear (PMNL) cells, we have used monoclonal antibodies in flow cytometry to estimate CD4, CD25, CD45, and HLA-G content. HLA-G serum levels were determined by ELISA. We observed a correlation between sHLA-G serum levels and liver function tests. After a month of HLA-G decrease in serum levels, liver function tests such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), direct bilirubin (DB), total bilirubin (TB), and alkaline phosphatase (ALP) were above normal levels, suggesting liver dysfunction or rejection. Considering these results, we concluded that the increased sHLA-G in serum and on cell surfaces may afford preliminary data on the prognosis and response to treatment in liver transplant patients.
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PMID:Human leukocyte antigen-G, a new parameter in the follow-up of liver transplantation. 1654 78

To study abnormalities in liver associated enzymes and histology in AIDS patients with common infections like hepatotrophic viruses and mycobacteria. 30 cases of HIV/AIDS were studied for any significant pattern emerging. The male:female ratio was 4.26:1, occupation being long-distance truck drivers (30%); migrant goldsmiths (27%); migrant labourers (24%). Duration of illness from onset was within three months (46%) and the maximum duration was 26 months (2%). The most common presentation was fever (90%), weakness (79%), weight loss (62%) and diarrhoea (62%). The CD4 cell count was between 200-500/microL (33%). LFT showed hyperglobulinemia in patients having CD4 cell count <500/microL. Rise of alkaline phosphatase was seen in 63% with CD4 cell count <200/microL. 66.6% had HBsAg reactivity, 33.3% had positive anti-HCV antibody and 50% had abnormal liver histology. One third of these had systemic opportunistic infections like tuberculosis. No correlation could be made between hepatic histology and LFT.
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PMID:Disordered structure and function of liver in HIV/AIDS--a study of thirty cases. 1693 22


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