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P F Zangerle

Publications and source records attributed to P F Zangerle.

11 recordsLinked to original sources
PubMed1992

Direct stimulation of cytokines (IL-1 beta, TNF-alpha, IL-6, IL-2, IFN-gamma and GM-CSF) in whole blood: II. Application to rheumatoid arthritis and osteoarthritis.

Rheumatoid arthritis (RA) is an immune disease in which the pathological immune reaction is thought to be initiated by the presentation of an (auto) antigen or superantigen by MHC class II positive cells to CD4 T cells. These successive immunological events can be studied by the cytokines produced at the different stages. Cytokine secretion by stimulated cells in autologous diluted whole blood has allowed the study of the immune profile characteristic of rheumatoid arthritis. The pattern of RA patient whole blood cells cultured in autologous blood is characterized by hyperactivity of the mononuclear cells with high secretion of IL-1 beta, TNF-alpha and IL-6 and low production of IFN-gamma, in comparison with the normal (N) and osteoarthrosis (OA) populations. The IL-2 secretion pattern is unique, arising from production followed by consumption. This production-consumption turnover is the most elevated in the RA group. The T cells are indeed activated in rheumatoid arthritis but regulatory events suppress some of their functions. A correlation was found between the inflammatory proteins and mediators of cellular immunity and macrophagic function: IL-1 beta and the sedimentation rate; IL-6 and fibrinogen; TNF-alpha and the number of blood monocytes. The secretion of OA-stimulated whole blood cells was similar to RA for two monokines (overproduction of TNF-alpha and IL-6) and different for IL-1 beta, not different from normal in OA. Stimulated whole blood cell cytokine secretion profile from RA and OA groups, was the same as previously observed in synovial fluid.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Direct stimulation of cytokines (IL-1 beta, TNF-alpha, IL-6, IL-2, IFN-gamma and GM-CSF) in whole blood. I. Comparison with isolated PBMC stimulation.

Production of interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), interleukin 2 (IL-2), interferon gamma (IFN-gamma) and granulocyte-macrophage colony-stimulating factor (GM-CSF) after stimulation by lipopolysaccharide (LPS) and phytohemagglutinin (PHA) was studied in 1/10 diluted whole blood (WB) culture and in peripheral blood mononuclear cell (PBMC) culture. Cytokines IL-1 beta, TNF-alpha and IL-6 are preferentially stimulated by LPS whereas IL-2, IFN-gamma and GM-CSF are stimulated by PHA. Combination of 5 micrograms/ml PHA and 25 micrograms/ml LPS gave the most reliable production of the six cytokines studied. IL-1 beta, TNF-alpha and IL-6 represent a homogeneous group of early-produced cytokines positively correlated among themselves and with the number of monocytes in the culture (LeuM3). Furthermore, IL-1 beta was negatively correlated with the number of T8 lymphocytes. IL-2, IFN-gamma and GM-CSF represent a group of late-produced cytokines. Kinetics and production levels of IL-6 and GM-CSF are similar in WB and PBMC cultures. In contrast, production levels of TNF-alpha and IFN-gamma are higher in WB than in PBMC whereas production levels of IL-6 and IL-2 are lower in WB than in PBMC. Individual variation in responses to PHA + LPS was always higher in PBMC cultures than in WB cultures. The capacity of cytokine production in relation to the number of mononuclear cells is higher in WB, or in PBMC having the same mononuclear cell concentration as WB, than in conventional cultures of concentrated PBMC (10(6)/ml). Because it mimics the natural environment, diluted WB culture may be the most appropriate milieu in which to study cytokine production in vitro.

Adult↗
PubMed1990

Neurophysins as markers of vasopressin and oxytocin release. A study in carcinoma of the lung.

Vasopressin-neurophysin (hNpI), oxytocin-neurophysin (hNpII) and blood osmolality were assayed before any treatment in basal conditions in 35 patients suffering from lung carcinoma (20 oat cell, 6 undifferentiated and 9 well-differentiated epidermoid cell carcinomas). Plasma vasopressin (antidiuretic hormone, ADH) was also assayed in 7 of the 20 patients suffering from oat cell carcinoma. We found a close correlation (r = 0.98) between plasma ADH and hNpI levels in the 7 patients. Further, hNpI was elevated in 13 out of the 20 oat cell carcinoma patients and in none of the epidermoid-cell carcinoma group; however, searching for an abnormality of ADH secretion as reflected by a detectable plasma hNpI level together with subnormal plasma osmolality revealed 2 additional positive results in the oat cell carcinoma group, and 2 out of the 6 in the undifferentiated-cell carcinoma group. hNpII was increased together with an increase in hNpI in 6 oat cell carcinoma patients; it was specifically increased without hNpI increment in 2 additional oat cell carcinoma patients and in 2 patients of the undifferentiated-cell carcinoma group (different from the 2 positive for the hNpI-osmolality ratio). hNpI and hNpII were normal in the majority of undifferentiated and all of the differentiated epidermoid-cell carcinoma group. Hence, our results show that simultaneous measurements of hNpI, hNpII, and blood osmolality could detect abnormalities in 17 out of 20 oat cell carcinoma patients, in 4 of the 9 undifferentiated-cell carcinoma patients, but in none of the differentiated epidermoid-cell carcinoma patients, suggesting that the neurophysin assay can be used for the early detection of oat cell- and possibly other neuroendocrine-derived carcinomas.

Biomarkers, Tumor↗
PubMed1985

Validation of radioimmunoassay for human lactalbumin in the serum by testing the endogenous antibodies interference.

For re-establishing the value of human lactalbumin as a functional marker of normal and pathological activity of the breast a sensitive and specific radioimmunoassay was established with the prior important control of the interference of endogenous antibodies. The specificity of the assay was assessed by the absence of interference from other proteins in milk or in breast cyst fluid, various hormones and tumor markers. Bovine lactalbumin showed incomplete and weak cross-reactivity. By an enzymoimmunoassay method it was shown that all the 222 human sera studied contain IgG immunoglobulins which bind bovine and human lactalbumin with greater reactivity of children's serum and without relationship to the blood groups. The maximum affinity constant of these endogenous immunoglobulins determined by the radioimmunoassay method is 4.5 times greater for bovine (Kd = 18 X 4(-11) M) than for human (Kd = 4 X 10(-11) M) lactalbumin. These endogenous anti-lactalbumin immunoglobulins caused no interference in the radioimmunoassay as shown by the complete correlation between the concentrations of human lactalbumin previously incubated and added to sera containing high-affinity antibodies and those measured directly in the radioimmunoassay. This lack of interference was explained by the higher (22-fold) affinity constant of the rabbit antiserum against human lactalbumin (Kd = 9 X 10(-12) M). The study of endogenous antibodies by the two enzymes and radioimmunoassay methods is needed before assessing and using a radioimmunoassay of human lactalbumin in serum.

Animals↗
PubMed1978

Casein and other tumor markers in relation to cancer of the breast.

Five tumor markers can be simultaneously determined in the serum by radioimmunoassay: carcinoembryonal antigen (CEA), alpha-fetoprotein (alpha-FP), human chorionic gonadotropin (HCG), beta-subunit of HCG (beta-HCG) and kappa-casein. In a series of 935 healthy subjects, these antigens remain detectable or are detected within very precise limits. At the start of the clinical evolution of breast cancer, the incidence of pathological concentrations is increased as compared with the highest level observed in normal subjects. This high incidence is mainly due to a concomitant determination of CEA, kappa-casein, HCG and beta-HCG. The alpha-FP test is never positive, while the kappa-casein concentration is particularly high in the first clinical stages of breast cancer and with metastases. The concomitant determination of these tumor markers may be a biological element contributing to the diagnosis of neoplasia, although it is neither an absolute nor a specific criterium. Indeed, a pathological concentration of at least one antigen was observed in 5.5% of the subjects presenting with benign mastopathy. When metastases occur (25 patients), the incidence of pathological concentrations of at least one antigen increases: 88%, the absolute values of these levels increasing simultaneously. The determination of the antigen concentration therefore allows an evaluation of the extension of the disease. Surgical removal reduces the incidence of positivity of these antigens to 34%. Persistence of pathological levels seems to be related to a possibility of relapse or metastatic spreading. Finally, chemotherapy and radiotherapy applied on a tumor which is not excised, does not decrease the incidence of positivity of the tumoral markers, although their levels seem to fluctuate with the clinical evolution.

Adult↗
PubMed1976

Simultaneous assays of cancer-associated antigens in various neoplastic disorders.

Five tumor markers were measured simultaneously in serum by radioimmunoassay: carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), human chorionic gonadotrophin (HGC), the beta subunit of HCG, and Kappa casein. In a population of 935 normal subjects these antigens were undetectable or found within precise limits. In patients with tumors of various origins the rate of pathologically elevated levels was 72% at the beginning of the clinical course (194 cases). This high rate was primarily due to the simultaneous measurement of CEA, betaHCG, HCG, and casein. AFP was of little importance. The simultaneous measurement of these tumor markers may be one biochemical element of diagnosis of carcinoma, although this criterion is neither absolute nor specific, as 14.7% of patients with non-neoplastic disorders (234 cases) were positive for one antigen. In the presence of metastases (112 cases) the rate of pathologic levels of at least one antigen was increased: 86% due to CEA and casein assay at the same time as their absolute levels were increased. Surgical removal reduces the rate of positivity of these antigens to 37%. As was shown in patients with breast cancer, the rate was 10% when the tumor had been removed at Stage N- and 54% when it was removed at Stage N+. Thus, the persistence of pathologic levels could be correlated with the capacity for recurrence or metastases. Finally chemotherapy, radiotherapy, or both, do not decrease the rate of positivity of the tumor markers.

Adult↗
PubMed1975

[Radioimmunologic assay of alpha-fetoprotein in various normal and pathological conditions].

AFP can be measured by radioimmunoassay in 52 hours using an incubation at 18 degrees C for 48 hours and the double antibody solid phase method to separate the free labelled AFP from the labelled AFP bound to the antibodies. In these conditions, the sensitivity and precision of the assay are very satisfactory and the results are directly in correlation with the results obtained using the classical double antibody method. In the serum of normal people, except pregnant women, the concentration of AFP is not detectable or is less than 20 ng/ml. In the serum of pregnant women, AFP increases from the 8th. week of gestation to the 32nd., then stabilises or gradually decreases.

Carcinoembryonic Antigen↗