Predictive indicators of rejection or infection in renal transplant patients.
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Biomarkers↗
Biomedical subjects
V Daniel
Publications and source records attributed to V Daniel.
Association of elevated blood levels of pentachlorophenol (PCP) with cellular and humoral immunodeficiencies.
It has long been suspected that pentachlorophenol (PCP) exerts a damaging influence on the immune system. In this study, the possible relationship between blood levels of PCP and immune function was studied in 190 patients who had been exposed for more than 6 mo to PCP-containing pesticides. The patients suffered from frequent respiratory infections and general fatigue. Lymphocyte subpopulations, in-vitro responses to mitogens, allogeneic stimulator cells, plasma neopterin, cytokines, soluble cytokine receptors, soluble adhesion molecules, and immunoglobulin autoantibodies were determined. A dose-response relationship between blood levels of PCP and cellular and humoral immune parameters was established. Blood levels of PCP were associated negatively with (a) total lymphocyte counts (p = .0002), CD4/CD8 ratios (p = .0015), and absolute counts of CD3+ (p < .0001), CD4+ (p < .0001), CD16+ (p < .0001), CD25+ (p = .0003), DR+ (p < .0001), CD8+/56+ (p = .020), and CD19+ cells (p = .092); (b) plasma levels of interleukin-2 (IL-2) (p < .0001), soluble IL-2R (p < .0001), IL-6 (p < .0001), IL-10 (p = .0039), interferon-gamma (IFN-gamma) (p < .0001), tumor necrosis factor-alpha (TNF-alpha) (p < .0001), transforming-growth factor-beta2 (p = .023), soluble IL-1 receptor antagonist (sIL-1 RA) (p < .0001), soluble intercellular adhesion molecule-1 (p = .0003); and (c) immunoglobulin (Ig) M-anti-Fab type autoantibodies (p = .0353). PCP levels were associated positively with (a) number of impaired stimulation assays per patient (p = .041); (b) number of circulating CD11b+ monocytes (p = .0015); and (c) plasma levels of neopterin (p < .0001), IL-4 (p = .020), and sIL-6R (p = .020). Compared with patients who had PCP plasma levels that were less than or equal to 10 microg/l, patients with blood levels of PCP that exceeded 10 microg/l experienced the following more often: low numbers of total blood lymphocytes (p = .054), CD3+ (p = .0014), CD4+ (p = .0001), DR+ (p = .0003), CD16+ (p = .0033), and CD25+ cells (p = .0033). In addition, the same aforementioned patients experienced the following more frequently: undetectable plasma levels of IL-2 (p = .0057), IL-6 (p = .042), IL-8 (p = .038), IL-10 (p = .0001), TNF-alpha (p = .0062), and IFN-gamma (p = .016); and impaired in-vitro responses of lymphocytes (p = .071). The authors concluded that increased blood levels of PCP were associated significantly with cellular and humoral immunodeficiencies. Recurrent respiratory infections and general fatigue could originate from PCP-associated immunosuppression.
Adolescent↗
Impaired in-vitro lymphocyte responses in patients with elevated pentachlorophenol (PCP) blood levels.
Immune parameters were examined in 188 patients who were exposed for more than 6 mo to pentachlorophenol-containing pesticides. Blood levels of pentachlorophenol, lymphocyte subpopulations, in-vitro responses to mitogenic and allogeneic stimulation, plasma neopterin levels, and plasma cytokine and cytokine receptor levels were determined. Impaired in-vitro lymphocyte stimulation responses were impaired in 65% of the patients. The likelihood of impaired lymphocyte stimulation increased significantly with levels of pentachlorophenol that exceeded 10 microliters/l (p < .05). Patients who had high blood levels of pentachlorophenol and abnormal lymphocyte stimulation also had increased proportions of blood monocytes in blood (p < .05), as well as increased IL-8 serum levels (p < .02). Eleven patients who had abnormal mitogen stimulation experienced decreased CD4/CD8 ratios of < 1.0; 5 of these patients had decreased CD4+ lymphocyte counts of < 500/microliters, and 3 patients had increased plasma neopterin of > 15 nmol/l. These results indicate that increased levels of pentachlorophenol in blood can lead to severe T lymphocyte dysfunction.
Adolescent↗
Regulatory elements controlling the basal and drug-inducible expression of glutathione S-transferase Ya subunit gene.
The synthesis of the glutathione S-transferase Ya subunit is induced in the mammalian liver by chemicals such as phenobarbital and 3-methylcholanthrene. To study the mechanism of this induction, the 5'-flanking region of a mouse glutathione S-transferase Ya subunit gene was fused to the structural gene for chloramphenicol acetyltransferase. The fusion gene was introduced into hepatoma cells for the assay of the expressed acetyltransferase activity. At least two cis-regulatory elements were identified in the 5'-flanking region of the Ya gene: one, responsible for the basal level of expression, is present in the sequence up to -0.2 kb; another, responsible for the inducible expression by aromatic compounds such as beta-naphthoflavone and 3-methylcholanthrene, is located in the sequence from -0.2 kb to -1.6 kb. The inducible element was functional only in cells with normal aromatic compound receptors, and it retained responsiveness to beta-naphthoflavone when transfected into homologous (mouse) or heterologous (rat, human) hepatoma cells. A 150-bp region upstream from the transcription initiation site of the mouse Ya gene was investigated for cis-acting transcriptional elements that are recognized by specific DNA-binding proteins. We show by DNase I foot-printing assays using extracts from liver nuclei that the Ya gene promoter contains, in addition to the TATA and CCAAT boxes, a more distal element that binds a protein which is probably related to the family of nuclear factor 1 (NF1).
Animals↗
Impact of heavy metals on hormonal and immunological factors in women with repeated miscarriages.
In 111 women with repeated miscarriages, the urinary excretion of heavy metals was determined in a challenge test with the chelating agent 2,3-dimercaptopropane-1-sulphonic acid in addition to hormonal, chromosomal, immunological and uterine investigations. The heavy metal excretion was correlated to different immunological (natural killer cells, T cell subpopulations) and hormonal (progesterone, oestradiol, prolactin, thyroid stimulating hormone) parameters. We conclude that heavy metals seem to have a negative impact on ovarian as well as on pituitary function. The heavy metal-induced immunological changes may interfere with the physiological adaptation of the immune system to the state of pregnancy with the result of a miscarriage. The observed heavy metal-induced hormonal and immunological changes may be important factors in the pathogenesis of repeated miscarriages.
Abortion, Habitual↗