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Biomedical subjects

H Wachter

Publications and source records attributed to H Wachter.

At least 199 records · Page 11Linked to original sources
PubMed1992

Tetrahydrobiopterin-dependent formation of endothelium-derived relaxing factor (nitric oxide) in aortic endothelial cells.

Inhibition of tetrahydrobiopterin (H4biopterin) biosynthesis in endothelial cells almost completely abolished the agonist-induced formation of endothelium-derived relaxing factor (EDRF) (NO). This inhibitory effect could be antagonized when H4biopterin biosynthesis was restored by activating a salvage pathway. These data indicate that the formation of EDRF strictly depends on the presence of intracellular H4biopterin, which, in addition to Ca2+, may represent a further physiological and/or pathophysiological regulatory of endothelial NO synthases.

Animals↗
PubMed1992

Biliary neopterin for differentiation between liver allograft rejection and viral graft infection.

Differential diagnosis between rejection and infection of a liver graft still represents a major problem. Rising concentrations of neopterin in serum or urine sensitively indicate rejection or infectious complications after renal, cardiac or bone marrow transplantation. Neopterin has been shown to be even more sensitive when measured locally, e.g. in the pancreatic juice of patients after pancreas allotransplantation. In the present study, we measured urinary and, for the first time, biliary neopterin concentrations in nine liver allograft recipients during the early post-transplant period.

Bile↗
PubMed1992

Association between serum-soluble CD8 levels and parameters of immune activation in patients with human immunodeficiency virus infection.

We compared the serum concentrations of soluble CD8 with the immune activation markers neopterin, interferon-gamma, tumour necrosis factor-alpha, soluble CD4, and with CD4+ and CD8+ T-cell counts in patients with human immunodeficiency virus (HIV) infection. The majority of patients had increased concentrations of soluble CD8, interferon-gamma and neopterin, and various significant correlations existed between them. Our results support the view that enhanced soluble CD8 levels indicate activated CD8+ T cells in patients with HIV infection.

Adult↗
PubMed1992

Immunization with tween-ether-treated SIV adsorbed onto aluminum hydroxide protects monkeys against experimental SIV infection.

In order to examine the efficiency of an AIDS vaccine potentially acceptable for human use we have investigated a split vaccine. Since such vaccines are safe and efficient, they have been in use for many years to protect man against enveloped RNA viruses, e.g., influenza and measles. Seven rhesus monkeys were immunized at Week 0, 4, 8, and 16 by im injection of 2 ml of vaccine containing 140 micrograms of Tween-ether-disrupted SIVmac251/32H adsorbed onto aluminum hydroxide. The immunized animals and three nonvaccinated control monkeys were challenged 2 weeks after the last immunization by iv injection of 10 to 50 minimal monkey infectious doses of SIVmac251/32H. Four of seven immunized animals did not show any signs of virus replication and therefore appeared to be protected. Nonvaccinated control animals and the vaccine failures showed a rise in their urinary neopterin concentrations 1 to 2 weeks after infection. At the end of the second week and thereafter, cocultures and polymerase chain reaction of their peripheral blood lymphocytes were positive. After the challenge, control animals and infected vaccinees showed a primary or secondary antibody response while antibody titers declined in virus-negative animals. Specific cytotoxic T-lymphocytes were not present prior to challenge, but were present in some animals thereafter. Therefore, these seem to reflect a response to viral replication rather than to immunization. Prior to challenge the CD4-positive lymphocytes of the peripheral blood of the four virus-negative animals only proliferated after exposure to the immunizing antigen. Thus, this reaction appears to predict protection.

Adjuvants, Immunologic↗
PubMed1992

Neopterin production in acute schizophrenic patients: an indicator of alterations of cell-mediated immunity.

This longitudinal study analyzed how the activation of cell-mediated immunity (CMI) was related to the severity of symptomatology in 25 acute schizophrenic inpatients (DSM-III-R, 295.31). Neopterin, which was used to monitor the activation of T-cells and macrophages, was found to be within the normal range, but the lowest neopterin concentrations were measured on day 0. By day 3, a significant increase of neopterin was observed. Compared with healthy controls, patients had significantly lower neopterin levels at baseline. The highest scores on the Clinical Global Impressions Scale and the Brief Psychiatric Rating Scale occurred on day 0 and decreased significantly over the observation period. In general, the increase of neopterin was accompanied by a decrease in psychopathological symptoms. These results' indicate that at study entry, when patients are acutely ill, activation of the CMI is reduced rather than increased. Possible pathophysiological mechanisms are discussed.

Adult↗
PubMed1992

Serum kynurenine and neopterin concentrations in patients with cardiomyopathy.

Serum kynurenine and neopterin concentrations were determined in patients with hypertrophic (n = 22) and dilated (n = 23) cardiomyopathy. Significantly increased kynurenine and neopterin levels have been observed in cases of dilated cardiomyopathy. In these patients we found a positive correlation between serum kynurenine and neopterin levels (RS = 0.52, P less than 0.001). There existed several associations between the laboratory parameters neopterin and kynurenine and clinical findings, such as left ventricle (LV) systolic volume and LV circumferential fiber shortening velocity in patients with dilated cardiomyopathy (all P less than 0.05). In vitro, interferon-gamma induces the formation of neopterin in human monocytes/macrophages. Also the degradation of tryptophan via the kynurenine pathway is induced by interferon-gamma. Our data show that increased kynurenine as well as neopterin accumulation in serum are associated with severity of dilated cardiomyopathy. Thus, the data point to a role of immune activation in the pathogenesis of the disease.

Biopterins↗
PubMed1992

[Cellular immunity in pregnancy-induced hypertensive diseases].

Cytokines (IL-1, sIL-2R, IL-3, IL-6, TNF-alpha, IFN-gamma, GM-CSF and neopterin) were measured in sera of 37 patients with hypertensive disorders of pregnancy, 10 healthy pregnant and 10 healthy non-pregnant controls. With the exception of neopterin (p = 0.004) there were no statistically significant differences in cytokine concentrations between healthy pregnant and non-pregnant controls. No statistically relevant differences between healthy pregnant women and hypertensive patients could be found in cytokines of T-lymphocytic origin except GM-CSF in patients with HELLP syndrome (p = 0.02). Elevated levels of IL-6, TNF-alpha and neopterin were observed in hypertensive women. Differences to healthy pregnant controls were statistically significant for IL-6 (p = 0.008), TNF-alpha (p = 0.009) and neopterin (p = 0.04) and were more pronounced in severe forms of the disease. These 3 parameters of monocytic origin showed significant positive correlations amongst each other. A participation of cell-mediated immunity (especially monocytes/macrophages) in the pathomechanism of hypertensive disorders of pregnancy can thus be assumed.

Biopterins↗
PubMed1992

Immunization of rhesus monkeys with high- and low-dose Tween-ether-disrupted SIVMAC.

Two vaccine trials were conducted with low- and high-dose purified Twen-ether-treated SIVmac adsorbed onto aluminum hydroxide using rhesus macaques. In the first experiment 7 macaques were immunized with a total amount of 560 micrograms protein and 3 animals served as controls. After the immunization period the vaccinees exhibited ELISA titers up to 1:1280 and 5 immunized animals showed an antigen-specific proliferative response. After the virus challenge the 3 control animals and 3 vaccinees became infected. Four of the infected animals developed a cytotoxic T-cell response beginning 8 weeks postchallenge. The 4 protected animals were rechallenged 16 weeks later and all became infected. For the high-dose experiment 5 immunized animals receiving 2 mg of antigen and 2 control animals were used. The ELISA titers of the vaccinees reached 1:20480 and 4 animals exhibited an antigen-specific proliferative response. In response to virus challenge the 2 control and 1 immunized animal became infected. From these data it can be concluded that the high-dose immunization scheme elicited higher antibody titers and increased the fraction of protected animals.

Adjuvants, Immunologic↗
PubMed1992

Urinary and pancreatic juice neopterin excretion after combined pancreas-kidney transplantation.

The aim of this study was to investigate excretion of urinary and pancreatic juice neopterin in patients after combined pancreas-kidney transplantation and to relate it to the clinical course. The study design was a prospective observation study. Thirty consecutive patients with end-stage diabetic disease received a simultaneous pancreas-kidney transplant with pancreaticocystostomy and temporary exteriorization of pancreatic juice. In 30 patients urinary neopterin (UN) was measured daily from day +1 until hospital discharge by high-performance liquid chromatography; in ten of these 30 patients pancreatic juice neopterin (PJN) was additionally analyzed daily from day +1 for as long as pancreatic juice was diverted to the exterior. Elevated urinary neopterin levels were observed in acute cellular rejection (19/24 rejection episodes) and in bacterial infection (9/16 cases)--however, increments were more pronounced in acute cellular rejection. In contrast, pancreatic juice neopterin increased in all seven observed pancreatic graft rejection episodes. Pancreatic juice infection did not result in a rise in pancreatic juice neopterin excretion. Patients without postoperative complications exhibited stable and low urinary/pancreatic juice neopterin levels. The highest urinary neopterin levels were observed in CMV disease. Levels measured prior to discharge from hospital did not correlate with graft and patient survival. Evaluation of urinary and pancreatic juice neopterin, although nonspecific, helps identify patients with an uncomplicated or complicated clinical course. Pancreatic juice neopterin appears to be superior to urinary neopterin in early detection of pancreatic graft rejection. This may be of particular importance in monitoring nonuremic pancreas allograft recipients.

Adult↗
PubMed1992

Lymphocyte subsets and beta 2-microglobulin expression in chronic hepatitis C/non-A, non-B. Effects of interferon-alpha treatment.

Thirty-three patients with chronic hepatitis C/non-A, non-B were included in a randomized controlled study of interferon-alpha 2b (IFN-alpha 2b) treatment, 3 x 10(6) U three times weekly for 36 weeks. Using an immunoperoxidase technique, frozen liver biopsy specimens were examined with MoAbs for the presence of T helper cells (CD4), T suppressor/cytotoxic cells (CD8), total T cells (CD2) and B cells (CD22) before and after treatment. beta 2-microglobulin (beta 2-MG) expression on hepatocytes was semiquantified using a scoring system on sections from paraffin-embedded biopsy specimens. Serum levels of beta 2-MG were analysed with a radioimmunoassay technique. Intralobular T helper and T suppressor/cytotoxic cells declined significantly in the treated patients but not in the controls. The portal CD4/CD8 ratio did not change. Before treatment, serum beta 2-MG levels and hepatocyte beta 2-MG expression were significantly higher in patients with chronic active hepatitis compared to patients with chronic persistent hepatitis. Serum beta 2-MG levels increased significantly in responders during IFN treatment, with a maximum after 12 weeks. However, in the liver, the hepatocyte beta 2-MG expression was significantly decreased after treatment. Thus, IFN-alpha treatment does not seem to induce an increased HLA class I antigen hepatocyte expression in chronic non-A, non-B hepatitis, which favours the hypothesis that its anti-viral effects are more important in modulating the disease activity.

CD4-CD8 Ratio↗
PubMed1992

Association between the activation of macrophages, changes of iron metabolism and the degree of anaemia in patients with malignant disorders.

In this study, we investigated a possible association between the degree of macrophage activation - as measured by serum neopterin concentrations - and disturbances of iron metabolism, determined by the concentrations of ferritin and serum iron, in patients with malignant disorders. Additionally we evaluated correlations between these factors and the degree and type of anaemia. Seventy-three patients, who suffered from non-Hodgkin's lymphoma (NHL) (n = 43), Hodgkin's disease (n = 11), myeloma or monoclonal gammopathy of unknown significance (n = 9), myelodysplastic syndrome (n = 1), and solid tumours (n = 9), were examined. Mean neopterin levels were raised in all groups, patients with NHL showing the highest concentrations. Ferritin but not neopterin concentrations were higher in males than in females. A significant correlation was found between neopterin and ferritin concentrations (p less than 0.01). Considering only female patients the strength of the correlation was the same (p less than 0.02). In addition, we found inverse correlations of neopterin with haemoglobin and iron concentrations (all p less than 0.01). Similar relationships existed in patients during follow-up. Our results support the hypothesis of an association between the degree of activation of macrophages and the development of anaemia by a shift or iron towards the storage sites.

Adult↗