Showing papers on "Neopterin published in 1988"
TL;DR: Neopterin studies reveal that preactivation of cell-mediated immunity is associated with poor prognosis in cancer patients and in human immunodeficiency virus infection, neopterin levels increase in parallel with progressive disease, are inversely correlated with CD4 + /CD8 + T-cell subset ratios and are of predictive significance.
585 citations
Journal Article•
TL;DR: Enhanced neopterin biosynthesis does not necessarily relate to activation of T cells but can also be caused by non-immune stimuli, and stimuli such as alloantigens or TNF-alpha can indirectly enhance neopter in release by their capacity to induce production of endogenous IFN-gamma.
Abstract: Recently we presented evidence that cellular immune responses are associated with increased in-vitro and in-vivo excretion of neopterin (Huber et al., 1983) and that, in vitro at least, macrophages and IFN-gamma play a key role in the induction of this phenomenon (Huber et al., 1984). Although this marker is increasingly applied for monitoring of human disease, there is limited knowledge about the mechanism(s) responsible for its increased biosynthesis during inflammatory states. To further elucidate this question we evaluated neopterin and IFN-levels in culture supernatants of human blood cells and in patients' sera. Cells or patients were exposed to a panel of recombinant cytokines, alloantigens or lipopolysaccharide. To investigate indirect stimulation by induction of production of endogenous IFNs, the impact of neutralization of IFNs by addition of specific antibodies was also studied. The data confirm our previous results which identified the monocyte/macrophage as the main producer cell among human blood cells. They further demonstrate that, at least in vitro, IFN-gamma, IFN-alpha and LPS can all stimulate neopterin release independently from each other. Thirdly, they indicate that stimuli such as alloantigens or TNF-alpha can indirectly enhance neopterin release by their capacity to induce production of endogenous IFN-gamma. On the basis of these data we conclude that enhanced neopterin biosynthesis does not necessarily relate to activation of T cells but can also be caused by non-immune stimuli.
85 citations
TL;DR: Most of the tested variables appear to present information not yet covered by the SENIEUR variables, and various ways for a possible revision or extension of the SENieUR Protocol are discussed.
82 citations
TL;DR: Increased and decreased neopterin serum levels in untreated and treated SAA patients, respectively, suggest modulation of endogenous lymphokine release subsequent to immunosuppression, which clearly support previous reports on abnormal lymphokines production in severe aplastic anemia.
79 citations
TL;DR: The data suggest that a possible dysregulation of IFN gamma, interleukin-4 or other lymphokine interleucine production may be related to increased IgE and IgG4 production and seems to be an important factor in the pathogenesis of AD.
Abstract: In vitro interferon-gamma (IFNγ) and neopterin generation by peripheral blood mononuclear cells (PBMC) from 15 patients with severe atopic dermatitis (AD) and 10 healthy controls was investigated. A s
66 citations
TL;DR: Urinary neopterin levels were above normal in 49 of 51 patients with viral hepatitis and elevations during the course of hepatitis showed a pattern similar to that of the usual liver biochemical tests, suggesting that neopterIn levels were related to the clinical activity of the viral disease.
49 citations
TL;DR: It is demonstrated that both interferons, IFN-gamma andIFN-alpha, the latter only at a 400-fold higher concentration, can trigger monocytes/macrophages directly to secrete neopterin.
47 citations
Journal Article•
TL;DR: It appears that major attention has to be paid to the functional state of the kidney when studying neopterin serum and/or urine values, as it appears that under these prerequisites both methods of detection as well as both sample sources yield comparable results.
Abstract: Determination of serum and urinary neopterin levels was performed daily in 30 patients undergoing kidney transplantation for treatment of end-stage renal failure. Neopterin serum levels were determined by RIA and urinary excretion by HPLC. In parallel, the same samples were tested for creatinine content. Results indicated a strong correlation between the clearance of neopterin and creatinine. This correlation was independent of the extent of functional impairment as well as of the different causes of renal insufficiency. As a consequence, a strong relationship between serum and urinary neopterin levels was only obtained when values were corrected for different renal function by dividing them by the creatinine levels. It thus appears that major attention has to be paid to the functional state of the kidney when studying neopterin serum and/or urine values. It also appears that under these prerequisites both methods of detection as well as both sample sources yield comparable results.
40 citations
TL;DR: Neopterin concentrations increase earlier in the course of HIV-1 infection, before effects on T-cell subpopulations are detectable, and may further support the suggestion that neopterin measurement could be of use for monitoring infected subjects or predicting the progression of disease.
Abstract: We measured neopterin, a biochemical indicator for the activation of cell-mediated immune reactions, in urines from 105 individuals at risk of infection with human immunodeficiency virus-1 (HIV-1), 83 of whom were seropositive for antibody to HIV-1. We compared absolute numbers of T-cell subsets (CD4+ helper/inducer T-cells, CD8+ suppressor/cytotoxic T-cells), and the ratio of CD4+ T-cells to CD8+ T-cells with the urinary neopterin concentrations. Concentrations of neopterin in urine were inversely correlated with absolute numbers of CD4+ T-cells and with CD4+/CD8+ ratios in anti-HIV-1 seropositive subjects but not in those seronegative. Various statistical comparisons of the data further demonstrated that neopterin concentrations showed larger differences between anti-HIV-1 seronegative and seropositive subjects than absolute numbers of CD4+ T-cells or CD4+/CD8+ ratios. These results seem to indicate that neopterin concentrations increase earlier in the course of HIV-1 infection, before effects on T-cell subpopulations are detectable, and may further support the suggestion that neopterin measurement could be of use for monitoring infected subjects or predicting the progression of disease.
36 citations
TL;DR: The circadian rhythm of urinary neopterin in five healthy young men (about 25 years old) is documented, using voidings collected during 48 h at fixed 4-h intervals, with total variability (peak-trough difference) reaching 51%.
Abstract: Neopterin, a marker of cellular immune system activation, is produced by human macrophages after induction by interferon gamma (secreted by T-lymphocytes) and is eliminated mostly in urine. We have documented the circadian rhythm of urinary neopterin in five healthy young men (about 25 years old), using voidings collected during 48 h at fixed 4-h intervals. We repeated the experiment three times, one week apart. Neopterin was measured by high-performance liquid chromatography (HPLC). We clearly show a peak of the excretion of neopterin in the early morning (around 0630 hours +/- 2 h), with total variability (peak-trough difference) reaching 51%. Neopterin is commonly assayed in urinary fractions, so it is imperative to use urine specimens collected at the same time of day--e.g., the first morning urines--to avoid misinterpretation in follow-up of patients.
34 citations
TL;DR: It is concluded, tentatively, that in HIV-infected patients neopterin levels of 22 nmol/l and over may indicate the manifestation of AIDS in the year to come.
Abstract: The reliability of laboratory parameters for the prediction of impending manifestion of AIDS in HIV-1 infected patients was investigated. Over a mean observation period of approximately 1 year (5 to 33 months) 56 patients were studied. Eleven patients progressed to AIDS (group 1) and 45 remained free of AIDS-defining disease (group 2). Eight candidate-predictor variables were measured on each patient at the beginning of the observation period: neopterin, hemoglobin, lymphocytes, CD4 counts, CD8 counts, platelets, gammaglobulins, and erythrocyte sedimentation rate. In a linear discrimination analysis, a stepwise entry of these parameters into the discriminant function was effected according to which variable added most to the separation into groups 1 and 2. Neopterin proved to be most discriminating with no improvement of separation when adding further variables. Thus, a final allocation rule was computed using neopterin alone. This rule assigns neopterin levels above 21.9 nmol/l to group 1 and levels below to group 2. We conclude, tentatively, that in HIV-infected patients neopterin levels of 22 nmol/l and over may indicate the manifestation of AIDS in the year to come.
TL;DR: It is suggested that urinary neopterin excretion may be a good biochemical marker to assess the progression of tumor and a useful prognostic indicator in patients with hepatocellular carcinoma.
Abstract: KAWASAKI, H., WATANABE, H., YAMADA, S., WATANABE, K. and SUYAMA, A. Prognostic Significance of Urinary Neopterin Levels in Patients with Hepatocellular Carcinoma. Tohoku J. exp. Med., 1988, 155 (4), 311-318 - Urinary neopterin levels were measured by high-performance liquid chromatography in 15 patients with liver cirrhosis, 18 patients with hepatocellular carcinoma and 20 normal subjects. The mean levels of urinary neopterin in patients with hepatocellular carcinoma were significantly elevated (p<0.01) compared to those in cirrhotics and normal subjects, but did not significantly differ between cirrhotics and normal subjects. Urinary neopterin levels correlated significantly with tumor size in patients with hepatocellular carcinoma but not with serum α-fetoprotein. Hepatocellular carcinoma patients with high urinary neopterin levels appeared to have more serious hepatic dysfunction than those with normal urinary neopterin levels, and moreover, there was a significant difference (p<0.05) in survival between the two groups. These findings suggest that urinary neopterin excretion may be a good biochemical marker to assess the progression of tumor and a useful prognostic indicator in patients with hepatocellular carcinoma.
Journal Article•
TL;DR: The demonstrated state of enhanced immune activation in Dialysis patients might also help to explain accelerated development of AIDS in dialysis patients when infected with HIV.
Abstract: We studied 20 patients on long-term hemodialysis. Concentrations of neopterin and creatinine were quantified in serum and in exchange buffers before, during and after treatment sessions. Neopterin is a low molecular weight product released by human macrophages upon stimulation with interferon gamma. It permits the quantification of the level of cellular immune activation in vivo. Neopterin and neopterin/creatinine ratios were found to be significantly increased in all patients. When comparing 15 patients treated with acetate exchange fluid buffers versus 5 patients treated with hydrogencarbonate, neopterin levels did not differ. Statistical computations revealed that the length of time on dialysis contributed to the increase of neopterin concentrations. Higher grade of cellular immune activation was preferentially detectable in those patients who had been on dialysis for more than 1 year. The demonstrated state of enhanced immune activation in dialysis patients might also help to explain accelerated development of AIDS in dialysis patients when infected with HIV.
Journal Article•
TL;DR: Serum procollagen-III-peptide concentrations rose significantly after treatment, suggesting release of propeptide previously incorporated without cleavage into tissue collagen, and the combination of these biochemical and immunological parameters may allow assessment of the pathophysiological mechanisms responsible for liver disease in individual patients.
TL;DR: Peripheral blood cholylglycine levels in patients with hepatomegaly, reflecting the spillover of portal blood into the systemic circulation, were elevated 12-fold over values of patients without liver involvement.
Abstract: In 20 patients with hepatic or hepatosplenic schistosomiasis and 82 individuals infected with S. mansoni, but without liver enlargement, serum parameters reflecting the fibrotic process and hemodynamic alterations as well as immunomodulation were examined. Included as controls were 35 age- and sex-matched healthy individuals from the study region in Northeast Brazil. Peripheral blood cholylglycine levels in patients with hepatomegaly, reflecting the spillover of portal blood into the systemic circulation, were elevated 12-fold over values of patients without liver involvement. Procollagen-III-peptide, a cleavage product of collagen synthesis, was elevated in patients with hepatomegaly (P<0.001) but normal in uncomplicated cases. Immunomodulation was assessed by in vivo delayed hypersensitivity to recall antigens and by serum Β 2-microglobulin and neopterin, substances released in the context of lymphocyte activation. Neopterin, predominantly a macrophage product, was elevated most strikingly in hepatomegalic cases (P< 0.001). The possible interrelation between altered immune responses and excess fibrogenesis is discussed.
TL;DR: It is concluded that urinary neopterin excretion reflects one aspect of alveolitic "activity" in pulmonary sarcoidosis and that normal values probably indicate a favorable prognosis.
TL;DR: To assess influence of host response to interferon-β (IFN-β), on biochemical parameters, β-microglobulin (β2-M) and neopterin were evaluated in 15 and 12 patients respectively before and 24 h after treatment with IFN- β.
Abstract: To assess influence of host response to interferon-β (IFN-β), on biochemical parameters, β-microglobulin (β2-M) and neopterin were evaluated in 15 and 12 patients respectively before and 24 h after...
TL;DR: It is concluded that the expression of activation markers on PBL and the production of IFN gamma and neopterin reflect the early phase of alloimmune response induced by leukocytes, and is not a prerequisite for the development of FcR-blocking antibody, which is produced after pure platelet transfusion.
TL;DR: It is concluded that neopterin and beta-2-microglobulin represent useful markers for monitoring biological response to treatment with rTNF-alpha and IFN-gamma, and a clear correlation between these levels is failed.
Abstract: The effect of different doses of recombinant human tumor necrosis factor-α (rTNF-α) on serum levels of neopterin, β-2-microglobulin and interferon-γ (IFN-γ) was investigated in tumor patients. Twel...
TL;DR: The IFN concentrations were correlated significantly with mitogen‐induced blastogenesis, and high serum neopterin levels and decreased CD4/CD8 ratios were associated with diminished γ‐IFN levels.
Abstract: 65 patients belonging to known acquired-immune-deficiency-syndrome (AIDS) risk groups were tested for mitogen responsiveness to pokeweed mitogen, concanavalin A and phytohemagglutinin, percentages of peripheral blood CD4, CD8 and Leu7 lymphocyte subsets, serum neopterin levels, and gamma-interferon (gamma-IFN) concentrations in cell culture supernatants. Patients with clinical symptoms of human-immunodeficiency-virus infection showed reduced gamma-IFN production in vitro. The IFN concentrations were correlated significantly with mitogen-induced blastogenesis. High serum neopterin levels and decreased CD4/CD8 ratios were associated with diminished gamma-IFN levels. The percentage of Leu7 lymphocytes was increased in a group of patients with strikingly elevated gamma-IFN levels.
Journal Article•
TL;DR: Although there is no detectable differences in serum interferon levels between patients and controls, neopterin levels were elevated in patients with active disease, possibly indicating a localised activation of the interferons system.
Abstract: We examined the sera of 50 patients with anterior uveitis (AU) for the presence of interferon and neopterin, an interferon induced pteridine derivative. Neopterin release is induced by gamma interferon and it is a more stable compound. Our results indicate that although there is no detectable differences in serum interferon levels between patients and controls, neopterin levels were elevated in patients with active disease, possibly indicating a localised activation of the interferon system.
TL;DR: Findings seem to confirm Kaposi's sarcoma as an 'opportunistic neoplasia' and indicate neopterin as a useful prognostic marker.
TL;DR: The clinical suitability of neopterin as an adjuvant parameter in assessing therapeutic effects in lung or breast cancer could not be documented.
Abstract: The elevated neopterin levels observed in numerous haemotological diseases and parenchymatous malignomas suggested neopterin might be useful as a tumor marker. In a group of 60 patients suffering from advanced lung (18) or breast (42) cancer, serial determinations of serum neopterin were made before, during and after radiation and/or chemotherapy, during an observation period of 18 months, to check the potential value of neopterin in the therapeutic management of these tumor types. The neopterin profiles were compared with the clinical course and analysed with regard to response to therapy. Numbers of pathologically elevated serum neopterin levels were low. In only few cases was any agreement detected between changes in neopterin levels and therapeutic effects. Even chemotherapeutically induced depression in white blood counts generally did not increase serum neopterin levels. Thus the clinical suitability of neopterin as an adjuvant parameter in assessing therapeutic effects in lung or breast cancer could not be documented.
01 Mar 1988
TL;DR: The results indicate a close relationship between S-neopterin and lymphocytic alveolitis in sarcoidosis as reflected in bronchoalveolar findings.
Abstract: We have previously found elevated levels of serum (S-) neopterin in patients with active sarcoidosis. In the present study we therefore investigated the relationship between elevated S-neopterin and sarcoid alveolitis as reflected in bronchoalveolar (BAL) findings. Patients with elevated percentages of BAL-lymphocytes (n = 19) had significantly higher (p less than 0.01) S-neopterin levels (median 12.1 nmol/L) than those (n = 11) with normal percentages (median 8.5 nmol/L). Of 19 patients with elevated lymphocyte percentage 18 had increased S-neopterin. There was a significant correlation between S-neopterin levels and the concentration (p less than 0.01) as well as the percentage (p less than 0.05) of BAL-lymphocytes. On the other hand, no correlation was found between S-neopterin and the BAL-albumin/S-albumin ratios, the concentration of macrophages or the concentration of angiotensin converting enzyme in the BAL fluid. The results indicate a close relationship between S-neopterin and lymphocytic alveolitis in sarcoidosis. Furthermore, a possible relationship between elevated S-neopterin and the ratios of T helper to T cytotoxic-suppressor cells (TH/TC-S) in blood, assumed to reflect changes of the ratios in alveolitis, was examined. However, 34 of 37 sarcoid patients had TH/TC-S ratios within the normal range. The ratios of patients with normal and elevated S-neopterin did not differ.