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Biomedical subjects

F Paraskevas

Publications and source records attributed to F Paraskevas.

At least 37 records · Page 2Linked to original sources

Cancer and depression: cancer presenting with depressive illness: an autoimmune disease?

It is proposed that some cases of depressive illness in cancer patients may be caused by immunological interference with the activity of serotinin, one of the neurotransmitters thought to be implicated in depression. This interference could be mediated in two ways. Antibody induced against a protein released from cancer cells could, on the basis of cross-reactivity with CNS tissue, bind to receptors for serotonin and block them. Such primary antibodies could stimulate the production of anti-idiotypic antibodies, which would act as an alternative receptor for serotonin and reduce its synaptic availability.

Animals↗

Release and reconstitution of Fc receptors from normal human mononuclear cells.

Nylon-fibre non-adherent cells isolated from human peripheral blood, release their Fc receptors for IgG upon culture in vitro in medium containing 0-2% foetal calf serum. The majority of Fc+ nylon-fibre non-adherent cells was reconstituted using supernates from different cell populations of human peripheral blood. The best reconstituting activity was detected in the supernates from glass-adherent cells, or unfractionated Lymphoprep cells, while those obtained from nylon-fibre non-adherent cells gave variable results sometimes containing no activity at all. It was shown that reconstitution was achieved by the uptake of Fc receptors present in the supernate which inhibited Fc rosette formation. Inhibition was also achieved with supernates from peripheral blood cells of a patient with monocytic leukaemia. Only autologous but not allogeneic cell supernates could reconstitute Fc receptors. This suggests that the reconstitution of Fc receptors on peripheral blood Fc-IgG lymphocytes by monocytic cells is under genetic control.

Cell Adhesion↗

Surface membrane changes of T cells induced by syngeneic tumour cells. I. Formation and uptake of complexes of Ig and tumour antigens by T cells.

A large dose of tumour cells (10(7)) from two different tumours produced a significant increase of Ig-bearing spleen cells 6 h after intraperitoneal administration in syngeneic mice, like conventional antigens previously tested. Incubation of normal spleen cells in serum taken 6 h after administration of tumour cells reproduced in vitro the changes observed in the spleen cell population of the serum donors, demonstrating the presence of a cytophilic Ig, which was shown to be taken up by T cells. Serum collected 6 h after tumour cell inoculation contains also a 4S factor which can generate in vitro cytophilic Ig for T cells in the presence of a foreign soluble protein or tumour antigen. Extracts obtained from tumours cells, which were shown to contain tumour antigens, were labelled with 125I and mixed with the 4S factor and normal 7S Ig. Upon fractionation of the mixture, high molecular weight material containing radioactivity and 7S Ig were eluted in the void volume, well ahead of the position of both the tumour cell preparation and the 7S Ig. This material contained Ig cytophilic for splenic T cells and it is likely that it represents cytophilic complexes of Ig and tumour antigens. It is postulated that the cytophilic Ig detected in the serum of animals 6 h after injection of a large number of tumour cells represents cytophilic complexes of Ig and tumour antigens formed through the mediation of a soluble factor.

Animals↗

Surface membrane changes of T cells induced by syngeneic tumour cells. II. T-cell defects induced by small tumour cell inocula or tumour cell antigens.

Injection of a large number of tumour cells, like other strong immunogenic challenges, is followed within 6 h by the uptake of cytophilic Ig (probably complexes) by a subpopulation of T cells. This phenomenon, known as the "6-hour T-cell response" is abrogated when small tumour cell inocula (10(2)), or small amounts of a preparation from tumour cells, which contains tumour antigens, are injected prior to the immunogenic challenge Abrogation of the "6-hour T-cell response" resulted in a decrease in specific anti-tumour cell immunity as tested in vitro by measuring growth inhibition (cytostasis). It has also resulted in loss of the amplifying function on antibody formation against sheep erythrocytes, normally detected in a T-B cell co-operative system when T cells are used 6 h after priming with sheep erythrocytes. It is postulated that this T-cell defect may represent a mechanism by which tumour cells, in the early stages of their growth, interfere with inductive stages of the immune response for a sufficient period of time to allow the tumour to grow beyond immune control.

Animals↗

Development of anti-hLH antibodies after therapy with posterior pituitary extract.

This report describes the appearance of high affinity antibodies to human LH in a girl who had been treated for diabetes insipidus with injections of pitressin tannate, plus occasional nasal insufflations of posterior pituitary powder. Immunological studies indicated that the antibody was a 7S IgG directed against the beta subunit of LH, which is not species-specific. The demonstration of immunoassayable LH in a commercially available pitressin preparation strongly suggests that this patient was immunized by bovine or porcine LH. Although studies of her urinary LH excretion and serum LH (by an interstitial cell bioassay system) suggest that at least some of her endogenous LH is not bound by the antibody, the possibility remains that this type of immunization may have important implications for the development and maintenance of normal adult pituitary-ovarian relationships.

Antibodies↗

Insidious rifampin-associated renal failure with light-chain proteinuria.

A patient who was receiving rifampin treatment for tuberculosis developed heterogenous light-chain proteinuria and insidious renal failure after a period of fluid restriction. The renal damage was characterized pathologically by an interstitial nephritis with invasive tubular casts and an associated renal vein thrombosis. The possible role of the light-chain proteinuria in the pathogenesis of the renal failure is discussed.

Acute Kidney Injury↗

The function of T cells carrying receptors for complexes of Ig and antigen.

Thymocytes exposed briefly in vitro to a variety of particulate substances (such as mycobacteria, erythrocytes of allogeneic cells) or to substances known to act in vivo as adjuvants (LPS or poly A:U), generate supernates which are able to induce cytophilic Ig in normal mouse serum in the presence of a foreign protein (antigen). This cytophilic Ig is taken up by 20-25% of splenic T cells. Hydrocortisone resistant thymocytes show the same property, while bone marrow cells are inactive. This activity is similar to that reported previously as being present in the 4S fraction of mouse serum, collected 6 hours after injection of complete Freund's adjuvant. It is proposed that this factor is responsible for the formation of complexes of Ig and antigen which have been detected in the serum 6 hours after immunization. Thymocytes collected 6 hours after priming in vivo with SRBC (when a subpopulation among them carries easily demonstrable surface Ig) are able to amplify markedly the antibody response particularly the 7S. It is postulated that the factor by generating the cytophilic Ig (complexes?) which is taken up by T cells, sets up a mechanism which markedly amplifies their helper cell function.

Adjuvants, Immunologic↗

Soluble factors in immune sera of mice. II. Reversible loss of surface immunoglobulin induced in vitro.

Serum collected from BALB/c mice at different time intervals during primary immunization induces in vitro a decrease of Ig+ cells in short-term cultures of normal spleen cells. The decrease was shown to be caused by loss of surface immunoglobulin (Ig) for the following reasons: no cell loss was detected which coulc account for it; the number of Ig+ cells returned to normal levels when the serum was removed and the cells were cultured further in fresh medium. The serum activity was recovered in a fraction with molecular weight less than 10,000 Daltons. The factor was active at 4 degrees C and on cells treated with high doses of Con A. Only a portion (25-30%) of the Ig+ cells are affected by this factor since after the initial decrease no further changes were observed during the 7 hr culture period. No changes in the distrubution of surface Ig was detected by fluorescent techniques on the remaining Ig+ cells. This factor was detected as early as 6 hr after immunization but its concentration was found 4-fold higher on the 7th day.

Animals↗

Soluble factors in immune sera of mice. I. Specific and non-specific suppressive activity.

Serum collected from mice 7 days following immunization with heterologous erythrocytes (SRBC, HoRBC) contained potent and specific immunosuppressive activity. When the serum was filtered through a Diaflo UM-10 membrane the activity was recovered in the filtrate, indicating that a factor less than 10,000 Daltons is responsible for it. Filtrates obtained from animals immunized with soluble antigens (BSA, POL) in FCA suppressed the 7S response to SRBC but had no effect on the 19S response. This non-specific suppressive effect on the7S response was also shown by filtrates obtained from sera of animals injected with FCA or other adjuvants (LPS, poly A:U). The 19S response to SRBC was either not affectd (LPS, poly A:U) or actually enhanced. (FCA). The SRBC-induced filtrates markedly suppressed the espression of DH to SRBC.

Animals↗