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)

Gene transfer to lung has been hindered by inflammatory and immunological responses activated to the gene-transfer agent or transgene products. In prior work, adenovirus vector delivered to the lung with the cationic glucocorticoid, dexamethasone-spermine (DS) had improved targeting to conducting airway epithelium and reduced cellular infiltration. In this study, the effect of formulation on homologous adenovirus vector re-administration was studied in C57Bl/6 mice. Formulation of an adenovirus vector expressing LacZ with DS/dioleoylphosphatidylethanolamine (DOPE) delivered at day 0 allowed re-administration of adenovirus vector expressing alkaline phosphatase at day 21. Formulation with 3beta [N-(N', N'-dimethylaminoethane) carbamoy] cholesterol (DC-Chol) DC-cholesterol (DC-Chol))/DOPE or dexamethasone in the first dosing at day 0 resulted in moderate alkaline phosphatase expression at day 24. Neutralizing antibodies against adenovirus vector in serum at day 28 were greatly reduced by all three formulations in mice receiving a single dose of adenovirus at day 0. Also, homologous adenovirus vector re-administration at day 14 produced less neutralizing antibody at day 28 when adenovirus was formulated with DS/DOPE at day 0. The use of DS/DOPE at day 0 dramatically reduced CD4 and CD8 T-cell infiltration in mice receiving adenovirus at day 0 followed by vector re-administration at day 14. Transgene-specific T-cell activation was markedly reduced by the DC-Chol/DOPE formulation. Overall, DS/DOPE) facilitated homologous vector re-administration through a combination of liposomal and glucocorticoid mechanisms.
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PMID:Pulmonary delivery of adenovirus vector formulated with dexamethasone-spermine facilitates homologous vector re-administration. 1789 95

T-cell activation requires the influx of extracellular calcium, although mechanistic details regarding such activation are not fully defined. Here, we show that P2X(7) receptors play a key role in calcium influx and downstream signaling events associated with the activation of T cells. By real-time PCR and immunohistochemistry, we find that Jurkat T cells and human CD4(+) T cells express abundant P2X(7) receptors. We show, using a novel fluorescent microscopy technique, that T-cell receptor (TCR) stimulation triggers the rapid release of ATP (<100 microM). This release of ATP is required for TCR-mediated calcium influx, NFAT activation, and interleukin-2 (IL-2) production. TCR activation up-regulates P2X(7) receptor gene expression. Removal of extracellular ATP by apyrase or alkaline phosphatase treatment, inhibition of ATP release with the maxi-anion channel blocker gadolinium chloride, or siRNA silencing of P2X(7) receptors blocks calcium entry and inhibits T-cell activation. Moreover, lymphocyte activation is impaired in C57BL/6 mice that express poorly functional P2X(7) receptors, compared to control BALB/c mice, which express fully functional P2X(7) receptors. We conclude that ATP release and autocrine, positive feedback through P2X(7) receptors is required for the effective activation of T cells.
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PMID:Autocrine regulation of T-cell activation by ATP release and P2X7 receptors. 1921 24

Trans-splicing adeno-associated viral (tsAAV) vectors hold great promise for delivering large therapeutic genes. One potential application is in the treatment of Duchenne muscular dystrophy (DMD). In this case, it is necessary to transduce whole body muscle. We demonstrated body-wide AAV-9 tsAAV transduction in normal neonatal mice. However, it was not clear whether such an approach would work in diseased mice. In this study we delivered the AAV-9 alkaline phosphatase (AP) tsAAV vector (3 x 10(12) vector genome particles per vector per mouse, tail vein injection) to 2-month-old mdx mice, the most widely used DMD model. Four months later, we observed widespread AP expression in the heart. It reached the same level as we have seen in normal neonatal puppy. Interestingly, myocardial transduction correlated with beta-myosin heavy chain expression but not with LamR, the putative AAV-9 receptor. AP expression was also detected in various skeletal muscles but at levels much lower than in normal newborn mice. Despite the existing inflammatory milieu, we did not see any appreciable increase in CD4(+) and CD8(+) T cells and macrophages in striated muscles after systemic tsAAV infection. In summary, our results have paved the way for tsAAV-mediated gene therapy for Duchenne cardiomyopathy.
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PMID:Systemic Trans-splicing adeno-associated viral delivery efficiently transduces the heart of adult mdx mouse, a model for duchenne muscular dystrophy. 2037 97

Studies of the physiological functions of intestinal epithelial cells (IECs) have been limited by the difficulty of primary culture of IEC. We established a method for primary culture of mouse IEC by culturing fragments of fetal small intestines pretreated with EDTA. This method reproducibly resulted in the expansion of cytokeratin-positive epithelial cells, and vigorous expansion of the epithelial cells was observed only from intestinal fragments of embryonic days 15-16. These cells expressed alkaline phosphatase activity and major histocompatibility complex (MHC) class II molecules, indicating the mature phenotype of IEC in a small intestine. The cells also presented antigens to CD4(+) T cells. Furthermore, the cells expressed various cytokines and chemokines, and the expression was enhanced by bacterial stimulation. These results indicate that the primary-cultured mouse IEC prepared by the method established here can be a beneficial tool in study of the functions of IECs, especially in mucosal immunity.
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PMID:Establishment of a primary culture method for mouse intestinal epithelial cells by organ culture of fetal small intestine. 1966 85

The immunomodulatory effects of Korean mistletoe lectin (KML), one of the major active components in Viscum album L. var. coloratum, were investigated in vitro in immune cell proliferation and natural killer (NK) cell- and macrophage-mediated cytotoxicity, and in vivo in the forced swim test and cold stress. In mitogen-induced lymphocyte proliferation of murine splenocytes, concanavalin A and lipopolysaccharide significantly increased the proliferation of T cell and B cell lymphocytes, respectively. KML exposure increased lymphocyte proliferation in response to mitogen. KML also increased the splenic NK cell and macrophage activities in vitro. Exposure to KML increased production of cytokines such as interleukin-1 and interleukin-6 by macrophages. Two-week treatment with KML (30, 100, 300 and 600 microg/kg) increased the recruitment of lymphocytes, monocytes and macrophages. In the forced swim test, the immobility time was significantly attenuated by treatment with KML (300 and 600 microg/kg). In a cold stress experiment, spleen and thymus weight increased in KML-treated mice, while the weight of adrenal gland was lower than that in vehicle-treated mice. The levels of serum aminotransferases, lactate dehydrogenase and alkaline phosphatase were decreased by KML treatment. KML treatment also induced increases in the percentages of CD4(+) and CD8(+) cells in thymus. Our results suggest that KML enhances the immune system through modulation of lymphocytes, NK cells, and macrophages.
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PMID:Immunomodulating effects of Korean mistletoe lectin in vitro and in vivo. 1978 34

In an effort to examine liver injury, immune response, and other physiological effects in mice caused by intragastric administration of nanoparticulate anatase titanium dioxide (5nm), we assessed T lymphocytes, B lymphocyte and NK lymphocyte counts, hematological indices, biochemical parameters of liver functions, and histopathological changes in nanoparticulate titanium dioxide -treated mice. Indeed, mice treated with higher dose nanoparticulate titanium dioxide displayed a reduction in body weight, an increase in coefficients of the liver and histopathological changes in the liver. Specifically, in these nanoparticulate titanium dioxide -treated mice, interleukin-2 activity, white blood cells, red blood cells, haemoglobin, mean corpuscular haemoglobin concentration, thrombocytes, reticulocytes, T lymphocytes (CD3(+), CD4(+), CD8(+)), NK lymphocytes, B lymphocytes, and the ratio of CD4 to CD8 of mice were decreased, whereas NO level, mean corpuscular volume, mean corpuscular haemoglobin, red (cell) distribution width, platelets, hematocrit, mean platelet volume of mice were increased. Furthermore, liver functions were also disrupted, as evidenced by the enhanced activities of alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase and cholinesterase, an increase of the total protein, and the reduction of ratio of albumin to globulin, the total bilirubin, triglycerides, and the total cholesterol levels. These results suggested that the liver function damage observed in mice treated with higher dose nanoparticulate titanium dioxide is likely associated with the damage of haemostasis blood system and immune response. However, low dose nanoparticulate anatase TiO(2) has little influences on haemostasis blood system and immune response in mice.
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PMID:Toxicological characteristics of nanoparticulate anatase titanium dioxide in mice. 1985 90

The aim of this descriptive cross-sectional study was to describe the prevalence of hypovitaminosis D in a cohort of HIV-seropositive males. Blood samples were collected in November and December 2004 and analyzed in the hospital laboratory. The concentration of 25-hydroxyvitamin D (25(OH)D) was defined as excellent when >75 nmol/l, normal when >50 nmol/l, insufficient when <50 nmol/l, deficient when <25 nmol/l and severely deficient when <12.5 nmol/l. Patient information was extracted from the medical records. A total of 115 males, median age 44 y (range 19-63 y), were included in the study. The median 25(OH)D concentration was 43.0 nmol/l (range 8-163 nmol/l) and the 25(OH)D level was excellent in 13%, normal in 27%, insufficient in 36%, deficient in 20%, and severely deficient in 4% of the cases. Vitamin D level was not associated with age, y with HIV infection, highly active antiretroviral therapy (HAART) or CD4 count. Compared to patients not in treatment, patients on HAART (n = 71) had higher levels of total alkaline phosphatase (median 83.0 vs 75.5 U/l; p = 0.031) and lower, though not significantly, total body mineral density (1.055 vs 1.107 g/cm(2); p = 0.077). This study confirms that the prevalence of hypovitaminosis is high among HIV-infected patients.
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PMID:Deficiency of 25-hydroxyvitamin D in male HIV-positive patients: a descriptive cross-sectional study. 2008 19

The aim of the present study was to investigate the antistress potential of LABISIA PUMILA aqueous extract (LPPM/A003) using a battery of tests widely employed in different stressful situations. Pretreatment of experimental animals with LPPM/A003 caused an increase in the swimming endurance and hypoxia time and also showed the recovery of physical stress-induced depletion of neuromuscular coordination and scopolamine induced memory deficit. LPPM/A003 at graded doses reversed the chronic restraint stress (RST), induced depletion of CD4 (+) and CD8 (+) T lymphocytes, NK cell population, and corresponding cytokines expression besides downregulating the stress-induced increase in plasma corticosterone, a major stress hormone. In addition, LPPM/A003 reversed the chronic stress-induced increase in adrenal gland weight, serum alanine aminotransferase (ALT), alkaline phosphatase (ALP), and hepatic lipid peroxidation (LP) levels and augmented the RST induced decrease in hepatic glutathione (GSH), thymus and spleen weight. Thus, we conclude that LPPM/A003 has the ability to reverse the alterations produced by various stressful stimuli and therefore restores homeostasis.
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PMID:Protective effect of Labisia pumila on stress-induced behavioral, biochemical, and immunological alterations. 2021 40

Fatigue is one of the most common and debilitating symptoms experienced by HIV-infected people. We report the results of our longitudinal analysis of physiological and psychosocial factors that were thought to predict changes in HIV-related fatigue in 128 participants over a 1-year period, in an effort to sort out the complex interplay among a comprehensive set of physiological and psychosocial variables. Physiological measures included hepatic function (aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transpeptidase, alkaline phosphatase, total bilirubin, hepatitis C status), thyroid function (thyroid stimulating hormone, thyroxine), HIV viral load, immunologic function (CD4, CD8, CD4/CD8 ratio, CD16, CD8CD38), gonadal function (testosterone, dehydroepiandrosterone), hematologic function (hemoglobin, hematocrit, serum erythropoietin), and cellular injury (lactic acid). Psychosocial measures included childhood and adult trauma, anxiety, depression, social support, stressful life events, and post-traumatic stress disorder (PTSD). Unemployment, not being on antiretroviral therapy, having fewer years since HIV diagnosis, more childhood trauma, more stressful life events, less social support, and more psychological distress (e.g., PTSD, anxiety and depression) put HIV-infected persons at risk for greater fatigue intensity and fatigue-related impairment in functioning during 1-year follow-up. Physiological variables did not predict greater fatigue. Stressful life events had both direct and indirect effects on fatigue.
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PMID:Physiological and psychosocial factors that predict HIV-related fatigue. 2035 17

A 73-year-old woman who had been diagnosed with systemic sclerosis was admitted for further examination of bilateral hilar lymphadenopathy. Sarcoidosis was confirmed based on elevated serum levels of angiotensin-converting enzyme, a high proportion of lymphocytes and a high CD4/CD8 ratio in bronchoalveolar lavage fluid, abnormal (67)Gallium uptake in the mediastinum and noncaseating granulomas in skin biopsy specimens. In addition, high levels of antimitochondrial M2 antibodies and alkaline phosphatase indicated primary biliary cirrhosis (PBC). Here we describe a rare triplex of sarcoidosis, SSc and PBC. Although the etiology of this complex remains unknown, these three diseases might share some pathogenesis.
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PMID:Sarcoidosis in a patient with systemic sclerosis and primary biliary cirrhosis. 2068 99


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