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Biomedical subjects

G Reibnegger

Publications and source records attributed to G Reibnegger.

At least 235 records · Page 13Linked to original sources

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↗

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↗

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↗

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↗

[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↗

Urinary neopterin levels in acute viral hepatitis.

Elevated neopterin levels in blood or urine have been shown to be a marker for the activation of cell-mediated immunity in vitro and in vivo. To evaluate whether neopterin levels are elevated in patients with acute viral hepatitis, we measured urinary levels in 13 patients with hepatitis A, 26 with hepatitis B, 12 with non-A, non-B hepatitis, 8 with jaundice and/or cholestasis due to biliary and pancreatic disorders and 3 with alcoholic hepatitis and in 62 apparently healthy HBsAg carriers. Neopterin levels in patients with virus-induced hepatitis were significantly higher than those in patients with other diagnoses. 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. In patients with nonviral biliary and hepatic disorders, neopterin levels were usually normal and did not correlate with other liver biochemical tests. These findings suggest that cell-mediated immune mechanisms are activated during viral hepatitis and that neopterin measurement may be of value as an additional surrogate marker for non-A, non-B hepatitis.

Acute Disease↗

Cerebrospinal fluid and serum neopterin levels in patients with Lyme neuroborreliosis.

Elevated (greater than 3.0 nmol/l) cerebrospinal fluid neopterin concentrations were observed in 20 of 21 patients with Lyme neuroborreliosis compared with three of 11 control patients with headache, back pain or psychoneurotic disorders. Neopterin concentrations were correlated to mononuclear cell counts and protein concentrations in the cerebrospinal fluid (CSF). Following antibiotic treatment, CSF neopterin levels decreased. Serum neopterin levels were not significantly raised in patients with neuroborreliosis when compared to control subjects. Neopterin levels as well as cell count and protein concentration in the CSF are valuable inflammation markers of disease activity in Lyme neuroborreliosis.

Adolescent↗

Serum concentrations of interferon gamma, interleukin-6 and neopterin in patients with infectious mononucleosis and other Epstein-Barr virus-related lymphoproliferative diseases.

Serum levels of interferon gamma, interleukin-6 and neopterin were determined in 15 patients with different forms of Epstein-Barr virus-associated diseases: acute self-limiting infectious mononucleosis, chronic active infectious mononucleosis and X-linked lymphoproliferative syndrome. In patients with acute type of infection, neopterin, interferon gamma and interleukin-6 were elevated in nearly all patients. In contrast, the situation was less clear-cut in the other EBV-associated diseases; particularly interleukin-6 was undetectable in most cases. The results suggest that concomitant measurement of these diverse immune activation markers may provide interesting insights into the interactions between the virus and the host, and may also lead to therapeutic consequences.

Acute Disease↗

Is schizophrenia linked to alteration in cellular immunity?

To reinvestigate the viral hypothesis of schizophrenia as well as possible immunological dysfunction, neopterin, which is an indicator of the activity in the cellular immune system, was determined in acute and chronic schizophrenics. Both diagnostic groups showed neopterin levels within the normal range. Patients with chronic schizophrenia of the residual type presented a significant dependency between neopterin concentrations and Brief Psychiatric Rating Scale (BPRS) total scores. In a long-term observation of 14 acute schizophrenic (paranoid type) inpatients, neopterin levels were found to be lowest at day 0. During the first week of treatment neopterin concentrations increased significantly whereas a concomitant decrease of the psychopathological symptoms could be observed. In comparison to healthy controls patients showed significantly lower neopterin levels at baseline. These findings will be discussed referring to the viral hypothesis of schizophrenia as well as to possible immunological alterations caused by stress or by changes in neurotransmitter synthesis.

Adult↗

Quantifying the 'appleness' or 'pearness' of the human body by subcutaneous adipose tissue distribution.

To quantify subcutaneous adipose tissue topography (SAT-Top) describing individual SAT distribution for a subject or even a group we measured subcutaneous adipose tissue thickness at 15 specified body sites of 303 healthy women aged 20-69 yrs and 20 women with proven non-insulin-dependent diabetes mellitus (NIDDM) by the optical device 'LIPOMETER'. The type of upper-body- and lower-body-fat pattern, (apples or pears), was determined by factor analysis of the data. Upper body sites were highly loaded in factor 1, whereas factor 2 included highly loaded body sites from the lower extremities. For an individual, factor 1 scores > factor 2 scores, was described as an 'apple'-type, while factor 2 > factor 1 was described as a 'pear'-type. We found about 80% 'pears' and 20% 'apples' in 20-29 year olds and 20% 'pears' and 80% 'apples' in 60-69 year old women. Women with NIDDM tended to be 'super-apples'. SAT-Top provides a useful differentiation between apples and pears and we recommend this approach as a screening method.

Adipose Tissue↗

Changes of serum neopterin, beta 2-microglobulin and interferon-gamma in patients with chronic hepatitis C treated with interferon-alpha 2b.

OBJECTIVES: Treatment with interferon (IFN) reduces viral replication and normalizes aminotransferase levels in a significant percentage of patients with non-A, non-B hepatitis or hepatitis C. Soluble immune activation markers were evaluated in patients with hepatitis. PATIENTS AND METHODS: Serum concentrations of soluble immune activation markers neopterin and beta 2-microglobulin (B2M) were compared to endogenous IFN-gamma levels in 17 patients with chronic hepatitis C before, during and after 9-months of treatment with IFN-alpha 2b. RESULTS: Before therapy some patients had increased concentrations of the studied variables. During therapy neopterin and B2M concentrations further increased whereas IFN-gamma decreased. IFN-gamma and neopterin levels were correlated before but not during therapy. The correlations between neopterin and B2M were significant throughout the study. CONCLUSION: The data indicate that IFN-gamma decreases during treatment and IFN-alpha 2b appears to enhance formation of neopterin and B2M.

Adult↗