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Biomedical subjects

D Fuchs

Publications and source records attributed to D Fuchs.

At least 523 records · Page 29Linked to original sources

Immune response-associated production of neopterin. Release from macrophages primarily under control of interferon-gamma.

Neopterin, a compound derived from GTP, represents a precursor molecule of biopterin that is an essential cofactor in neurotransmitter synthesis. We have recently reported that in vivo as well as in vitro immune responses are accompanied by an increased release of neopterin and that this phenomenon can be used for the biochemical monitoring of diseases accompanied by hyperimmune stimulation. This article deals with the cellular origin and the control of this immune response-associated neopterin release in vitro. Using highly purified or monoclonal cellular reagents we demonstrate that macrophages (M phi) stimulated with supernatants from activated T cells release large amounts of neopterin into culture supernatants. Further experiments involving induction of neopterin release from M phi with various human recombinant interferons (IFNs) or neutralization of the effect of T cell supernatants with various monoclonal anti-IFN antibodies revealed immune IFN as the active principle. It thus appears that a metabolic pathway so far exclusively known in context with the generation of an essential cofactor of neurotransmitter-synthesis during immune responses is also activated in M phi under stringent control by immune IFN-like lymphokines.

Biopterins↗

Urinary pteridines on patients suffering from cancer. A comment on the method and results of Rao and associates and of Trehan and associates.

A diagnostic test for detecting malignancies has been reported by Rao and associates. This test has been extended by Trehan and associates as an index of disease status in acute myeloblastic leukemic patients on antileukemic drugs. The authors were able to demonstrate that by using the described assay various pteridines are measured and not exclusively 6-hydroxymethylpterin as reported by the above-mentioned authors. Furthermore, the urinary component which correlates to the status of malignant disease has to be interpreted as being neopterin. This conclusion can be drawn from previous studies conducted by the authors' laboratory.

Biopterins↗

[Neopterin, a new biochemical marker for clinical assessment of cell-mediated immune response].

Activated T-lymphocytes represent crucial effector cells. They are pathogenetically involved into various disease states such as allograft rejection or viral infection. So far their assessment is laborious and rarely possible in clinical routine. In this review article we present the compount neopterin as a new biochemical marker for the in vivo and in vitro detection of activated T-lymphocytes. Our main finding was that in vitro as well as in vivo stimulation of T-lymphocytes with foreign and chemically or virally modified autologous cells in invariably associated with increased neopterin production. It thus appeared that neopterin might represent a potential marker for biochemical monitoring of diseases caused by or associated with T-lymphocyte activation. Our clinical experience with neopterin determination in allograft rejection and in infectious or autoimmune states strongly support this view. We conclude that evaluation of neopterin represents a useful and simple tool for the biochemical monitoring of immunological and/or malignant states.

Adolescent↗

Neopterin as a new biochemical marker in the clinical monitoring of bone marrow transplant recipients.

In previous reports we demonstrated that increased amounts of the pyrazinopyrimidine compound neopterin are released in the context of T lymphocyte activation. The aim of this investigation was twofold: (1) to define the contribution of hemopoetic cells to neopterin excretion, and (2) to search for the clinical utility of this biochemical marker in the monitoring of such patients. Thirteen patients were grafted with allogeneic, 1 with syngeneic, and 2 with autologous marrow. Urinary neopterin excretion was measured daily by means of high-performance liquid chromatography from the time before transplantation until the patients' discharge from the isolation unit. In all patients bone marrow aplasia was associated with depressed, and engraftment with increased, neopterin values. Rising neopterin levels invariably preceded the cytological definition of "take," on the average by seven days. After hematological reconstitution, neopterin excretion continuously declined in all 5 patients lacking infectious complications and/o-graft-versus-host disease (GVHD). A transitory increase of urinary neopterin followed by normalization was observed in 5 further patients. At the time of increased neopterin excretion, 4 experienced either herpetic infection or GVHD, both of which resolved promptly under the appropriate treatment. Neopterin values remained elevated after engraftment in 6 patients who suffered from persistent GVHD. Results of this pilot study suggest that (1) bone marrow derived cells are crucially involved in production of neopterin in vivo and (2) evaluation of neopterin excretion patterns after hemopoietic reconstitution enables one to discriminate between patients with and without an increased risk of developing GVHD or viral disease.

Biopterins↗

Measurement of urinary 7,8-dihydro-6-hydroxylumazine in healthy and in Ehrlich ascites tumour-bearing mice.

An estimation of 7,8-dihydro-6-hydroxylumazine in urinary samples of mice by high performance liquid chromatography on reversed phase material is presented. Urinary samples are diluted with water and oxidized by iodine. Chromatographic elution is done isocratically using aqueous buffer containing methanol. Effluent 6-hydroxylumazine is monitored by its fluorescence (382 nm excitation, 449 nm emission). The described method can be performed rapidly with satisfactory accuracy and precision. The electrochemical detection of 7,8-dihydro-6-hydroxylumazine was studied additionally. Total values of daily excreted 7,8-dihydro-6-hydroxylumazine of healthy and of Ehrlich ascites tumour-bearing mice were measured.

Animals↗

[Digital image information systems in radiology--status and developmental trends].

A digital image information system is expected to increase the efficiency of image acquisition and reporting. In addition to the requirements of the radiology department the requirements of the wards and the theatres must also be taken into account. The image information system has to be linked with the administrative work flow throughout the department. Therefore, it must provide interfaces to a radiology management system. In the United States such an image information system is referred to as "Picture Archiving and Communication System" = PACS. A suitable systems concept and the requirements of a real system are pointed out. The available technical solutions are discussed as well as the probable trends of future developments.

Computers↗

Urinary neopterin in the diagnosis and follow-up of neoplasia: a biochemical parameter to detect cell-mediated immune response.

Neopterin is excreted at high levels during disease states challenging the T-lymphocyte-macrophage system. Stimulation of T-lymphocytes in mixed lymphocyte culture in the presence of macrophages is accompanied by raised neopterin levels in the supernatant. Neopterin may therefore be considered a specific indicator of cell-mediated immunity. Pretreatment analysis of patients with hemopoietic (191), urological (82) and gynecological (224) neoplasia revealed neopterin levels above the upper normal limits, with frequencies ranging from 57% (cervical carcinoma) to 96% (chronic lymphocytic leukemia). In patients with tumors of the genitourinary tract or with hemopoietic neoplasms, urinary neopterin levels were correlated with the tumor burden and became normal when remission was achieved. In gynecological cancer long term follow-up studies showed the value of neopterin excretion levels as a tumor marker. Tumor progression was indicated early by a rising neopterin level. Based on a comparison of different tumor types, the association of cell-mediated immunity and of neopterin excretion levels in less differentiated neoplasm is discussed.

Adolescent↗

Measurement of urinary neopterin in normal pregnant and non-pregnant women and in women with benign and malignant genital tract neoplasms.

Urinary neopterin was measured in healthy women (n = 209) and men (n = 208), in patients with benign gynecological tumors (n = 53), in women with precancerous lesions of the cervix and the endometrium (n = 24) and in women with cancer of the genital tract (n = 108). In addition urinary neopterin measurements were made in 109 pregnant women and 20 women in the puerperium. No significant difference was found between mean neopterin values in patients with benign gynecological tumors, in women with precancerous lesions and in healthy women. Patients with cancer had significantly higher mean urinary neopterin levels than the control group. Raised neopterin levels were found in 56% of patients with genital tract cancer, the figures varying between 93% for ovarian cancer and 47% for cancer of the cervix. Some of the cancer patients had serial urinary neopterin measurements and in about 80% there was some relation between urinary neopterin values and clinical progress as judged clinically and radiologically, the best agreement existing in patients with ovarian cancer. Significantly higher mean neopterin values were found during normal pregnancy and in the early puerperium than in non-pregnant healthy controls. Raised urinary neopterin excretion may be due to enhanced cell proliferation and alloantigenic activation of T-lymphocytes.

Adolescent↗

Test performance of language-handicapped children with familiar and unfamiliar examiners.

The importance of examiner familiarity to children's performance on tasks requiring high or low levels of symbolic mediation was investigated. Thirty-four handicapped preschool children were examined within a repeated measures crossover design, once by one of two familiar classroom teachers and once by one of four strange teachers. Subjects performed significantly better with familiar than with unfamiliar examiners on high symbolic mediation tasks; no such differential performance was obtained on low symbolic mediation items. Findings are related to current efforts to identify procedural and situational variables in assessment, uncontrolled by present standard test administrations, that may preclude children's optimal performance.

Child, Preschool↗

Neopterin as a new biochemical marker for diagnosis of allograft rejection. Experience based upon evaluation of 100 consecutive cases.

The use of daily urinary neopterin evaluation to detect immunological complications has been tested in 96 consecutive cadaveric kidney recipients, three liver recipients, and one pancreas recipient. In 29 of these patients an immunologically uncomplicated posttransplant course was associated with stable or low neopterin levels, or both. In only 5% of daily determinations on these patients were increasing or high neopterin levels seen. On the other hand, major immunological complications, such as acute rejection episodes (38 cases), viral infections (17 cases), or both problems (8 cases), were preceded by increasing or high neopterin levels or both--on the average by one day. Withdrawal of cyclosporine was also found to be followed by increase of urinary neopterin levels. Neopterin evaluation enabled reliable and accurate prediction of immunological complications in 95% of patients with acute rejections and in 100% of patients with viral infections. It thus appears that daily assessment of urinary neopterin levels represents a useful tool for biochemical detection of immunological complications in allograft recipients.

Biopterins↗

Elevated urinary neopterin levels in patients with the acquired immunodeficiency syndrome (AIDS). A preliminary report.

Neopterin excretion in urine of patients with AIDS was measured by high pressure liquid chromatography. Urinary neopterin levels in patients with generalized lymphadenopathy, which is considered to be part of the spectrum of AIDS, as well as in severe AIDS cases were significantly elevated, compared to normal controls. This finding may prove useful as a screening test for donors of blood products in order to prevent transmission of AIDS by this route.

Acquired Immunodeficiency Syndrome↗

Pteridines as a new marker to detect human T cells activated by allogeneic or modified self major histocompatibility complex (MHC) determinants.

Evidence is presented that activation of T cells by allogeneic or modified autologous cells leads to the specific production of two distinct molecular compounds of the PT class. One of these two PT has previously been identified as neopterin. The structure of the other is still under investigation. This conclusion was based on the following findings: a) In vitro both PT were produced by T cells proliferating in response to HLA incompatible allogeneic or to autologous EB-virus-transformed or TNP-haptenized cells. b) In vitro stimulation of T cells with mitogenic lectins or protein antigens, of macrophages with zymosan-complement, of B cells with PWM or EB-virus, and of NK effector cells with tumor targets failed to induce comparable release of these PT. c) In vivo increased amounts of both PT were excreted via the urine during allograft rejection and viral infections. It thus appears that the production of these PT is primarily a feature of activated T cells involved in the control of self integrity.

Adult↗