Optical investigation of the valency of Pr in Y1-xPrxBa2Cu3O7- delta.
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Biomedical subjects
Publications and source records attributed to D Fuchs.
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Seven of fourteen elderly female patients (mean age 82.3 [75-89] years) with abnormalities of cognition, memory and affect of organic causation were randomly assigned to be given cognitive training, especially relating to memory, as part of rehabilitation measures for medical or orthopaedic diseases. The other seven served as controls. Training extended over 15 days, cognitive training given on 9 days for 45 min each. The control group had sessions of nonspecific attention. All patients were given psychological tests of memory and attention before and after cognitive training (or nonspecific attention). Behavioural changes were also assessed. The patients with cognitive training scored significantly higher than the controls, both in the individual exercises of the training programme and in the various tests of performance. The cognitive training also favourably influenced social behaviour, mood and level of volition. Maintaining and improving still present mental capacity in this type of patient is an essential task within a hospital setting, which otherwise provides little stimulus. Cognitive training is simple and effective, yet of great social importance.
The percentage of activated, CD3+ DR+ and CD8+ Leu7+ lymphocytes and the serum neopterin concentration were determined in 17 HIV-seropositive and 10 HIV-seronegative haemophiliacs and in 11 healthy control subjects. All three parameters tested were found to be significantly higher in the seropositive patients than in the seronegative controls. In the seropositive group, a significant positive correlation was found between the neopterin levels and the percentage of CD3+ DR+ cells. By contrast, no significant negative or positive correlation was observed between the neopterin levels and the percentage of the CD8+ Leu7+ subset. These data suggest that in the HIV-infected patients the activated T cells responsible for the stimulation of macrophages to produce neopterin are those that do not carry CD8.
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IFN-gamma is the most effective principle responsible for IDO induction in human cells in vitro. Lymphocyte factors support the effect of other IFN species. Induction of IDO and influence of various factors on IDO is correlated to pteridine synthesis. Cooperative effects of several mediators may account for in vivo observations concerning enhanced excretion of neopterin and tryptophan metabolites in certain disease states.
Increased neopterin levels in urine and serum of living humans indicate an activation of the cellular immune system. We investigated 119 urine and 48 serum samples from 129 corpses taken at necropsy; 29 cases with a background of cellular immune activation were compared to 100 corpses with no such indication. Our investigations show the feasibility of postmortem neopterin measurements. However, different kinetics of serum and urine concentrations after death were observed. In addition, the data show that urine and serum neopterin concentrations were significantly higher when cellular immunological abnormalities were present when compared to the control group and to living healthy controls. The findings suggest, that increased postmortem urine neopterin concentrations in necropsy indicate pathological processes linked with cellular immune activation.
The great majority of individuals with human immunodeficiency virus type 1 (HIV-1) infection presents with no signs or symptoms, or only lymphadenopathy. To initiate prophylactic measures in time it is necessary to establish risk criteria. CD4+ cell counts are significant predictors. Supplementary methods to improve the predictive information of CD4+ cell counts are still required. In addition, CD4+ cell counting is laborious, expensive, and restricted to specialized laboratories. Thus, there is also a place for more easily performed laboratory tests with similar predictive value as CD4+ cell counts. Neopterin and beta 2-microglobulin levels proved to be significant predictors of AIDS risk in HIV-1 seropositives. The predictive value of both parameters is equal to CD4+ cell counts and both markers are significant joint predictors in addition to CD4+ cell counts. Measurement of the parameters is done in serum (neopterin and beta 2-microglobulin) or urine (neopterin) specimens which reduces the risk of HIV-1 transmission compared to handling of whole-blood samples as it is required for cell counting. Although more studies are needed, especially in developing countries and in persons receiving zidovudine, it can be recommended to use neopterin and beta 2-microglobulin as additional marker to estimate AIDS risk in HIV-1 seropositive individuals. Moreover, both markers may be useful for this purpose without CD4+ cell counts if cell counting is not available.
Nocturnal sleep was studied in 14 human immunodeficiency virus (HIV)-positive patients without opportunistic infections of the central nervous system. Seven patients had no bodily complaints at the time of the investigation. Patients exhibited an impaired nocturnal sleep with longer sleep onset latency, reduced total sleep time, reduced sleep efficiency, and more time spent awake and in stage 1. Stage 2 sleep was significantly decreased; in 2 cases, sleep spindle density was extremely low. REM latency was reduced and correlated negatively with depressive symptomatology, while the percentages of REM and slow wave sleep were normal. No significant differences in sleep parameters were present among patients in different stages of the illness, or between patients with and without bodily complaints. Ventricular size and sulcal width on computed tomography scans correlated with sleep variables indicating reduced sleep quality, and with REM density. Decreased tryptophan plasma levels were associated with shorter and less efficient sleep, and with reduced stage 2 sleep. The findings demonstrate that sleep EEG investigations can be valuable for detecting and monitoring central nervous system affection in HIV-positive individuals.
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Reduced tryptophan and increased kynurenine concentrations have been reported in patients with human immunodeficiency virus type 1 (HIV-1) infection. From in vitro data it appears that activated indoleamine 2,3-dioxygenase (IDO) is involved in this metabolic change. IDO is inducible by interferon-(IFN)-gamma. We compared serum concentrations of IFN-gamma and neopterin (the biosynthesis of which is also inducible by IFN-gamma) with serum, tryptophan and kynurenine of 42 patients with HIV-1 infection. IFN-gamma, neopterin and kynurenine levels were significantly increased compared to HIV-1 seronegative controls whereas tryptophan was significantly decreased. Various significant correlations were found between tryptophan, kynurenine, IFN-gamma and neopterin concentrations. Highest degree of correlation was found between neopterin, IFN-gamma and the kynurenine per tryptophan quotient which is the ratio between the product and the substrate concentration of IDO. The data indicate that decreased tryptophan in HIV-1 seropositives may result from chronic immune activation and can be referred to increased activation of IDO.
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Prostaglandin E2 (PGE2)-mediated monocyte (M phi) suppressor activity and inadequate T-helper cell function represent the mechanistic keystones of trauma-induced impairment of cell-mediated immunity (CMI). In a prospective randomized trial, the immunorestorative potential of a combined therapy with the thymomimetic substance Thymopentin (TP-5; Timunox, Cilag GMBH, Sulzbach, FRG) and the cyclooxygenase inhibitor indomethacin (Indo) in 60 patients (mean age, 63 +/- 2 years) undergoing open heart surgery was studied. Perioperative immunologic screening was carried out on days -2, 3, 1, 5, and 7 and included the in vivo delayed type hypersensitivity (DTH) skin response, phenotyping for peripheral blood mononuclear cell (PBMC)-specific and nonspecific induction of lymphoproliferative responses, in vitro interleukin-2 (IL-2) synthesis, as well as the serum concentration of D-erythro-Neopterin (NPT) and of gamma interferon (gamma-IFN). The study protocol comprised three groups (n = 20): PA (Indo 150 mg administered intravenously on days 0 to 5), PB (TP-5 administered subcutaneously on days 0, 2, 4, and Indo), and PC (control). In contrast to PC, significant immunorestoration could be demonstrated in PB, as DTH scores on day 7, as well as proliferative responses in cell cultures were not depressed after operation (p less than 0.05). Cell-surface receptor expression for the CD3+, CD4+, and IL-2 receptor-positive (IL-2R+) lymphocyte subpopulations following surgery was reduced to 75% of baseline values in PC, while in PB, receptor protection for CD4+ and IL-2R+ subpopulations (more than 15% above baseline) was observed. Interleukin-2 synthesis (average baseline value, 0.7 + 0.08 U/mL) in cell cultures of PC was massively suppressed, with lymphokine concentrations in the supernatants never more than 0.27 +/- 0.05 U/mL. In PA cultures, IL-2 synthesis was impaired as well but not as precipitously as in PC. In contrast, in PB cultures, the average IL-2 production on consecutive postoperative days was never below baseline values. This study clearly demonstrates that the combined Indo/TP-5 therapy is superior to single Indo administration and can adequately preserve and/or restore intact M phi T-cell interaction and thus appears to be a feasible approach to maintain normal host defense activity in traumatized individuals.
Hematopoietic disturbances are common in patients with HIV-1 infection. Recent studies on immune activation markers such as neopterin demonstrate that HIV-1 infection is associated with chronic immune activation. We investigated a possible association between serum neopterin concentrations and blood cell counts (CD4+ T cells, white blood cells, platelets, red blood cells) and hemoglobin and hematocrit in 94 HIV-1-seropositive individuals [52 Walter Reed (WR) stage 1, 31 WR2, one WR5, and 10 WR6]. There were significant negative correlations between neopterin concentrations and CD4+ T cells, hemoglobin, hematocrit and platelets. These correlations were also significant if either only WR1 and WR2 patients or the entire set of data were considered for calculations. Thus, hematological abnormalities are associated with chronic immune activation in patients with HIV-1 infection. Large amounts of neopterin are released by human macrophages on stimulation with interferon-gamma (IFN gamma), and tumor necrosis factor alpha (TNF alpha) further enhances the effect of IFN gamma. Therefore, our data suggest that activated immune cells and specific cytokines such as IFN gamma and TNF alpha are involved inhibiting hematopoiesis.
We evaluated the number and percentage of CD4+ T cells, the ratio of CD4+ T cells to CD8+ T cells, the serum levels of beta 2- microglobulin and urinary levels of neopterin for their ability to predict disease progression (defined as clinical AIDS and/or oral candidiasis in combination with a CD4+ T cell count less than 400 x 10(6)/l). Thirty-eight intravenous drug users (IVDU) infected with HIV-1 without HIV-1-related symptoms were followed for a median observation period of 45 months. Cumulative incidence of disease progression was computed by the product-limit approach. The CD4+: CD8+ T-cell ratio (P = 0.001), the number (P = 0.002) and percentage (P = 0.05) of CD4+ T cells, and urinary neopterin (P = 0.007) were significant predictors for disease progression. Serum beta 2-microglobulin, which has been found to be of similar prognostic value as neopterin in homosexual men, did not show predictive power in this study of IVDU. The urinary neopterin concentrations obtained at entry of the study correlated with the values of the CD4+:CD8+ T-cell ratio and number and percentage of CD4+ T cells which were obtained at the end of the follow-up. These findings should help to identify, among HIV-1-infected IVDU, those at high risk of disease progression.
During the immediate posttransplant period, daily measurements of urinary neopterin, which is produced by stimulated macrophages, were evaluated in 294 consecutive recipients of renal allografts for their diagnostic value in acute graft rejection. The ability of mean and peak neopterin excretion values to predict long-term graft survival was analyzed on the basis of an eight-year follow-up. Immunosuppressive therapy (cyclosporine +/- prednisone versus azathioprine + prednisone) and initial nonfunction did not influence neopterin excretion. In patients with rejection episodes and in those with infections, neopterin levels were significantly increased. Diagnostic sensitivity and specificity with regard to rejection diagnosis were assessed for different levels of neopterin. By statistical analysis, a significant association between increased neopterin and higher risk of rejection was found, which was particularly pronounced in patients receiving cyclosporine. Increase in neopterin excretion preceded clinical rejection diagnosis by up to four days. Peak neopterin values above 800 mumols/mol urinary creatinine observed during the posttransplant period, were associated with significantly poorer graft survival. A multivariate analysis showed that peak neopterin levels, age of patients, and early posttransplant presence/absence of acute rejection were significant and independent joint predictors for long-term graft survival. Measurement of neopterin can be of help as an additional marker in early diagnosis of renal allograft rejection, and high neopterin values during the initial posttransplant period are associated with poorer long-term graft survival.
In 1985 a high HIV-seroprevalence (44.2%) was found in a cohort of parenteral drug addicted prisoners in Innsbruck, Austria. In a longitudinal study from March 1985 to March 1989 we investigated the epidemiology of HIV-infection as well as possible changes in the drug taking behaviour of this defined population at risk. During the study HIV-seroprevalence rates in drug dependent prisoners showed a statistical decrease to 30%. A concomitant increase in admission to any kind of therapy programmes as well as an increasing change from 'heavy use' (mainly taking heroin i.v.) to 'non-heavy use' (mainly taking drugs orally) could be noted. The influence of preventive measures, such as comprehensive AIDS-information, special therapy programmes including the methadone substitution programme, and the unrestricted availability of needles and syringes is discussed.