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Biomedical subjects

A Hausen

Publications and source records attributed to A Hausen.

At least 127 records · Page 7Linked to original sources
PubMed1984

[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↗
PubMed1984

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↗
PubMed1984

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↗
PubMed1984

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↗
PubMed1983

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↗
PubMed1983

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↗
PubMed1983

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↗
PubMed1983

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↗
PubMed1983

Significance of urinary neopterine in gynecological oncology: follow-up of patients with ovarian cancer.

In patients with genital cancer (N = 108) significantly higher mean neopterine levels were found than in a healthy control group. Prior to therapy elevated neopterine levels were seen in 60% of the patients with cancer of the genitals varying between 90% (ovarian cancer) and 54% (cervical cancer). Nine patients with ovarian cancer (stages IIb-IV) were followed for a period of 16 months to date. All patients had elevated neopterine values prior to therapy. When the urinary neopterine excretion remained increased over the period of observation, progression of the tumor occurred within a few months. In patients with complete or partial remission of the tumor, the neopterine excretion dropped to normal values. Thus, we feel that neopterine sampling may be helpful in the follow-up of patients with ovarian cancer, as tumor progression is indicated very early, before clinicoroentgenological findings are present.

Adult↗
PubMed1982

Determination of neopterine in human urine by reversed-phase high-performance liquid chromatography.

Since the analysis of urinary neopterine is important in diagnosing malignancy, a method has been developed for its rapid and sensitive separation and quantitation using high-performance liquid chromatography (HPLC) on reversed phase. Eluted neopterine is monitored by fluorescence at a excitation wavelength of 353 nm and measured at 438 nm. Separation was optimized by elution with 15 mmol/l potassium phosphate (pH 6.4) at a flow-rate of 0.8 ml/min. Urinary neopterine was related to creatinine with the aim of reducing variations due to fluctuating urinary concentrations. The proposed method has good performance characteristics and is not influenced by the presence of reduced neopterine in urine. Using this HPLC method, urinary neopterine related to creatinine was determined for 148 healthy male adults (mean neopterine/creatinine 113 mumol/mol), 146 healthy female adults (mean neopterine/creatinine 140 mumol/mol) 60 healthy children (mean neopterine/creatinine 163 mumol/mol). The neopterine levels for four healthy individuals were measured daily over a period of one month.

Adolescent↗
PubMed1982

Urinary neopterine in the assessment of lymphoid and myeloid neoplasia, and neopterine levels in haemolytic anaemia and benign monoclonal gammopathy.

The urinary neopterine levels were measured by HPLC in 417 normal subjects and in 216 patients with haematological diseases. All patients with active malignancies (multiple myeloma, polycythaemia vera. Hodgkin's lymphoma, non-Hodgkin's lymphoma, chronic myelocytic and chronic lymphocytic leukaemia) showed highly elevated mean and median values compared to the control groups. Those of patients with multiple myeloma stage I were only raised to near the upper limit of healthy subjects. Of 123 patients with active disease 105 (85%) were above the upper limit. In contrast, the mean and median values of 56 patients with neoplasias in remission (Hodgkin's and non-Hodgkin's lymphoma, acute leukemia and multiple myeloma) were not different from those of healthy subjects, and only 7 (12.5%) of these patients had levels above the upper limit. In patients with non-malignant diseases (haemolytic anaemia and benign monoclonal paraproteinaemia) the mean and median values were not raised. In patients with non-Hodgkin's lymphoma and with chronic lymphocytic leukemia, the neopterine levels corresponded with the tumor stage. The present data suggest tht neopterine assay may supplement laboratory measurements in haematological diseases, providing helpful information.

Adolescent↗
PubMed1982

Urinary neopterine excretion in patient with genital cancer.

Urinary neopterine values in 96 healthy women were compared with those in a group of 63 patients with cancer of the genitals who had not yet undergone treatment. Significantly higher median neopterine levels were found in the patients with carcinoma (p less than 0.001). In the 63 cancer patients who had not yet been treated, the diagnosis was made correctly in 65% of the cases by monitoring neopterine levels. In the follow-up of 72 patients with cancer of the genitals in 74% the neopterine values corresponded with the clinico-roentgenological findings. In 22%, false positive neopterine values (no recurrence of the tumor), and in 4% false negative values (recurrence, or progression of the carcinoma) were observed. These results confirm previous reports concerning the significance of pteridine excretion in patients with cancer. However, more investigations have to be performed to establish the value of neopterine sampling in monitoring patients with malignant tumors.

Adult↗
PubMed1982

Pteridines in the assessment of neoplasia.

Biological processes which might explain the association of pteridine excretion with proliferation are still unknown. Difficulties in the analysis and the determination of naturally occurring pteridines are described. The best quantitative estimations were achieved when measurement of non-reduced forms was attempted. The performance characteristics of such a method for neopterin by high performance liquid chromatography on reversed phase are given. Enhanced proliferation and dedifferentiation in cell cultures and organisms is paralleled by excretion of unconjugated pteridines into the medium or urine. Urinary neopterin in healthy subjects and in patients with benign diseases was only significantly raised in patients with viral diseases. However, an elevation of urinary neopterin occurred in a wide variety of malignant diseases. In haematologic neoplasias correlations of neopterin values to clinical features, to tumour staging, and to laboratory data were apparent. The clinical utility of neopterin measurement was also demonstrated in patients with gynaecologic tumors, particularly in patients with ovarian carcinoma. In both homogeneous patient groups the neopterin assay may provide an additional aid for prognosis and for monitoring therapy. Comparison of the neopterin assay with already established tumor marker substances at least revealed no inferiority in sensitivity. The present results justify extensive investigations in order to evaluate further the clinical applicability of the neopterin assay.

Adolescent↗
PubMed1982

[Pteridine secretion as a marker for the proliferation of alloantigen-induced lymphocytes (author's transl)].

Pteridine levels from supernatants of mixed lymphocyte cultures and from urinary samples of allogeneic kidney transplant recipients were measured by high-pressure liquid chromatography. Marked proliferation of alloreactive lymphocytes was paralleled by an increased release of pteridines. In human allograft recipients rejection episodes were preceded at least 1-2 days by increased urinary neopterin levels. Thus, the urinary neopterin estimation is useful in the early detection of immunological rejections.

Cells, Cultured↗