Cellular immune activation and erythropoiesis in gynaecological cancer.
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Biomedical subjects
Publications and source records attributed to D Fuchs.
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Since October 1986, all volunteer blood donors in the Tirol of Austria have been tested for neopterin. Serum neopterin levels were raised in 1242 donors (1.6%), 650 of whom (52.3%) consented to another test four weeks after the donation. In retrospect, 148 of these donors (22.8%) had an illness or abnormal symptoms at the time of donation or within a few days of it: according to the "guidelines for blood group testing and blood transfusion" of the Federal German Chamber of Doctors (Deutsche Bundesärztekammer) 25 of these (16.9%) should be permanently excluded as blood donors. The other 123 donors would have been temporarily excluded, according to the guidelines, if their illness had been known at the time of donation. Since the beginning of 1988, all donated blood with increased serum neopterin levels also had an IgM test for cytomegalovirus (CMV): nine of 243 samples tested (3.7%) indicated an acute CMV infection. The neopterin assay thus detects a variety of potentially harmful diseases or conditions which would not be revealed by the usually employed battery of routine tests.
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The capacity of T lymphocytes to proliferate in response to stimulation and the amount of representative lymphokines produced in vitro often correlate with the immunocompetence of patients. However, direct and indirect measurement of endogenous interferon-gamma (IFN-gamma) brings some evidence that decreased in vitro production of IFN-gamma by T lymphocytes is associated with increased concentrations in vivo. The data indicate that both a functional inhibition of IFN-gamma and its continuous presence at high levels may result in hyporesponsiveness or unresponsiveness of immune cells. A possible role of IFN-gamma in the induction of tolerance is discussed.
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D-erythro-neopterin is excreted in high amounts from human monocytes/macrophages responding to stimulation with gamma interferon. In vivo, the determination of neopterin offers a convenient possibility for monitoring the activation state of the cell-mediated immune system. Neopterin concentrations in body fluids also are raised with high sensitivity in viral diseases, irrespective of the specific nature of the virus. Thus, neopterin concentrations also are raised in viral diseases the causative agent of which has not yet been characterized such as non-A, non-B hepatitis. Determination of neopterin concentrations is easily accomplished by chromatographic or immunological techniques. Clinical studies showing the behaviour of neopterin levels in viral diseases are reviewed with special emphasis laid on the behaviour of neopterin concentrations in body fluids during virus-induced liver diseases, particularly non-A, non-B hepatitis. The possibilities offered by this marker to reduce the risk of disease transmission via transfusion of blood or blood components are discussed.
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A mathematical analysis is presented for several simple dynamical systems that might be considered as crude descriptions for the situation when an immune system retrovirus, immune cells, and normal autonomously replicating pathogens interact. By stability analysis of the steady-state solutions, the destabilizing effect of the immune system retrovirus is described. The qualitative behavior of the solutions depending on the system parameters is analyzed in terms of trajectories moving in a phase space in which the axes are defined by the population numbers of the interacting biological entities.
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During a three-week period in March/April 1987, the authors examined 253 consecutive patients referred to a rural hospital in northwestern Tanzania. Sera were tested for antibodies to human immunodeficiency virus type 1 (HIV-1), human immunodeficiency virus type 2 (HIV-2), and human T-lymphotropic virus type I (HTLV-I), as well as for various parasites, hepatitis B virus, and Treponema pallidum. Neopterin (urinary and serum) was chosen as the immunologic parameter. In eight of the 253 patients (3.2%), a clinical diagnosis of acquired immunodeficiency syndrome (AIDS) was established. Three of the AIDS patients had HIV-1 antibodies, two had HIV-1 antigen, one had both HIV-1 and HIV-2 antibodies, and in one patient, only HIV-2 antibodies were found. The total HIV-1 and HIV-2 seroprevalence (antibodies plus antigen) was 4.3%; HTLV-I seroprevalence was 9.9%. No correlation could be found between HIV (or HTLV-I) seropositivity and raised levels of antibody to the above pathogens. There was, however, a significantly positive correlation between HIV seropositivity and history of gonorrhea, whereas a history of operations, injections, vaccinations, blood transfusions, or scarification did not influence the level of HIV seropositivity. The most frequently noted epidemiologic association with HIV seropositivity was traveling to or coming from Uganda or Rwanda. Two thirds of the studied Tanzanians had elevated neopterin levels, and all seven HIV-seropositive patients with clinical signs of AIDS had extremely high serum and urinary neopterin levels compared with HIV-seropositive patients without signs of AIDS. Increased neopterin levels reflect a stimulation of the T-cell/macrophage system.
Neopterin, a biochemical marker for the activation of cell-mediated immune reactions, was determined in serum and cerebrospinal fluid (CSF) from patients infected with HIV-1. A significant correlation was found between serum and CSF neopterin concentrations, although concentrations of neopterin in serum were more closely correlated with the clinical severity of HIV-1 infection than those in CSF. However, higher CSF levels were observed in patients with neurologic/psychiatric symptoms than in unaffected patients. Also, quotients of CSF neopterin versus serum neopterin concentrations were increased, indicating intrathecal production of neopterin. Positive HIV-1 isolation from peripheral blood mononuclear cells (PBMC) was associated with higher neopterin concentrations in serum, when compared with negative HIV-1 isolation. Neopterin in CSF appears to be a suitable biochemical marker in patients with HIV-1 infection for detecting overt neurologic/psychiatric disturbances. The data suggest that in HIV-1 infected patients, cell-mediated immune reactions might be activated intrathecally and might contribute to neuropsychiatric disease.
Two rhesus monkeys were infected with SIVmac 251. Elevated urinary neopterin concentrations were observed as the first sign of infection. Virus-specific antibodies were detected 14 days after infection, when neopterin concentrations were already decreasing. The neopterin levels of one animal remained elevated and the virus was repeatedly isolated. Urinary or serum neopterin concentrations appear to be early markers for SIV infection and viremia in rhesus monkeys.
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This article presents a quantitative synthesis of examiner familiarity effects on Caucasian and minority students' test performance. Fourteen controlled studies were coded in terms of methodological quality (high vs. low) and race-ethnicity (Caucasian vs. Black and Hispanic). An analogue to analysis of variance conducted on weighted unbiased effect sizes indicated that examiner familiarity produced a significant effect, with Caucasian and minority examinees' test performance raised by .05 and .72 standard deviations, respectively. Examiner familiarity's differential effect on Caucasian and minority examinees did not interact with the methodological quality of the studies. Nevertheless, limitations of the extant data base require caution in drawing implications for assessment practice.
This study assessed the effects of curriculum-based measurement (CBM) on teachers' instructional planning. Subjects were 30 teachers, assigned randomly to a computer-assisted CBM group, a noncomputer CBM group, and a contrast group. In the CBM groups, teachers specified 15-week reading goals, established CBM systems to measure student progress toward goals at least twice weekly, and systematically evaluated those data bases to determine when instructional modifications were necessary. Contrast teachers monitored student progress toward Individualized Education Program (IEP) goals as they wished and were encouraged to develop instructional programs as necessary. At the end of a 12- to 15-week implementation period, teachers completed a questionnaire with reference to one randomly selected pupil. Analyses of variance indicated no difference between the CBM groups. However, compared to the contrast group, CBM teachers (a) used more specific, acceptable goals; (b) were less optimistic about goal attainment; (c) cited more objective and frequent data sources for determining the adequacy of student progress and for deciding whether program modifications were necessary; and (d) modified student programs more frequently. Questionnaire responses were correlated with verifiable data sources, and results generally supported the usefulness of the self-report information. Implications for special education research and practice are discussed.
The capacity of recombinant interferon-alpha, -beta and -gamma, of bacterial lipopolysaccharide and of recombinant tumour necrosis factor-alpha to induce indoleamine 2,3-dioxygenase and synthesis of pteridines was studied in human peripheral blood mononuclear cells, human macrophages and normal dermal fibroblasts. The action of interferon-alpha and -beta on macrophages was supported by lymphocyte factors as indicated by the effect of these mediators in the absence or presence of lymphocytes. Tumour necrosis factor-alpha alone was ineffective in peripheral blood mononuclear cells and macrophages, but it significantly increased the action of all three interferon species on macrophages and fibroblasts. Lipopolysaccharide directly affected macrophages or dermal fibroblasts and enhanced the effect of interferon-gamma. However, in the presence of lymphocytes, the action of lipopolysaccharide was mediated via interferon-gamma.