Biomedical subjects
G Tsokos
Publications and source records attributed to G Tsokos.
On the origin of C3 nephritic factor (antibody to the alternative pathway C3 convertase): evidence for the Adam and Eve concept of autoantibody production.
The antibody to the alternative pathway C3 convertase, designated C3 nephritic factor or C3NeF, is an autoantibody that is produced in everyone from the time of birth. The elaboration of C3NeF utilizes germline V-region genes which undergo antigen-driven affinity maturation, resulting in an autoantibody that is produced in large amounts with high affinity and narrow specificity. Our data also suggest that under normal conditions, the idiotypic network may play an important part in the control of this autoantibody. Further, a defect in the network with loss of control or inappropriate stimulation may be an underlying mechanism in the unrestricted production of C3NeF in patients with membranoproliferative glomerulonephritis.
Mood effects of alternate-day corticosteroid therapy in patients with systemic lupus erythematosus.
Mood and cognition were assessed on consecutive days in 18 female patients with systemic lupus erythematosus on alternate-day corticosteroid therapy. No overall differences in mood and cognition were observed between the on- and off-medication days. However, 10 patients showed marked worsening or improvement of either depression or anxiety on their off-medication day. Two weeks of prospective behavioral ratings confirmed the observed mood changes in several patients. The clinical and theoretical implications of these findings are discussed.
Alternate-day corticosteroid treatment, mood and plasma HVA in patients with systemic lupus erythematosus.
Corticosteroid therapy may produce alterations in mood. Furthermore, several monoamines, including dopamine, have been implicated in the regulation of mood. We, therefore, examined the relationship between alterations in mood and plasma homovanillic acid (HVA) levels in patients on alternate-day corticosteroid treatment. Although several patients had substantial alterations in mood, there was no significant difference in plasma HVA levels between the on- and off-medication day. Furthermore alterations in depression and anxiety levels were not related to plasma HVA levels. The implications of these findings are discussed.
Immunocytochemical demonstration of glucocorticoid receptors in different cell types and their translocation from the cytoplasm to the cell nucleus in the presence of dexamethasone.
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A human lymphocyte mitogen extracted from the extracellular slime layer of Pseudomonas aeruginosa.
Slime glycolipoprotein of Pseudomonas aeruginosa has been found to exert a mitogenic effect on human peripheral blood and cord blood lymphocytes. The optimal concentration of glycolipoprotein was shown to be in the range of 100--200 micrograms/ml, and maximal incorporation of [14C]thymidine was seen on the fourth day of lymphocyte cultures.
A subpopulation of lymphocytes with T and B cell characteristics. Observations on two different cases of immunodeficiency.
We present the immunological studies on 2 patients, one with the Wiskott-Aldrich syndrome and another with common variable hypogammaglobulinemia. Although these patients represent two different immunodeficiency defects, both had a subpopulation of peripheral lymphocytes which had simultaneously T and B characteristics. Their peripheral blood mononuclear cells had a low responsiveness to polyclonal mitogens. We suggest that these unusual cells represent a subpopulation of suppressor cells or of immature T cells, which may have an essential role in the pathogenesis of these immunodeficiencies.
Chlorpromazine and lidocaine inhibit antibody-dependent cell-mediated cytotoxicity but not erythrocyte antibody rosette formation.
Pretreatment of human peripheral blood mononuclear cells with chlorpromazine and lidocaine reduces their ability to induce lysis of antibody-coated target cells. This effect of local anesthetics was not due to a reduction of binding of antibody-coated red cells to the mononuclear cells, but it was rather probably due to the inhibition of mobility of the Fc receptor on the cell membrane.
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.
Inhibition of complement-dependent rosette formation after lymphocyte incubation with fatty acids.
Overnight incubation of lymphocytes with certain fatty acids bound to albumin has previously been shown to modify the fatty acid composition of cellular phosphoglycerides without impairing viability, and also to inhibit mitogen and antigen-induced lymphocyte transformation. In the present study, incubation of human lymphocytes with palmitic acid or with linoleic acid impaired their capacity to form complement-dependent rosettes but had no effect on either spontaneous rosette formation with sheep erythrocytes or Fc(gamma)-dependent rosette formation. With mouse lymphocytes, complement-dependent rosette formation was suppressed only following incubation with linoleic acid and there was no effect on Fc(gamma)-dependent rosette formation. Although the mechanism of these effects remains to be elucidated the results suggest that control of membrane lipid composition may modify the important in vivo immunological functions which involve complement receptors.
HLA-B27 frequency in Greek patients with acute anterior uveitis.
The histocompatibility antigen HLA-B27 was identified in 12 out of 33 patients with acute non-granulomatous anterior uveitis. This is a frequency of 36.36%, compared with 4.72% in controls. Seven patients had in addition evidence of systemic disease, including ankylosing spondylitis, sacroiliitis, Reiter's disease, Still's disease, and rheumatoid arthritis. Five of these were HLA-B27 positive, which suggests that the uveitis in many of these cases has a similar aetiology to the uveitis in those with rheumatic disease. It appears that the more severe cases of acute anterior uveitis are related more frequently to the presence of HLA-B27.
Clinical significance of low creatine phosphokinase values in patients with connective tissue diseases.
We have noted that values for serum creatine phosphokinase (CPK) are frequently low in patients with connective tissue diseases. Geometric mean values were 96.0 units/L among 121 disease-free males and 50.2 units/L among 63 disease-free females. The geometric mean values were 31.7 units/L in 11 males and 35.2 units/L in 49 females with systemic lupus erythematosus; 15.1 units/L in three males and 13.0 units/L in ten females with rheumatoid arthritis; and 41.6 units/L in 19 females with Sjögren's syndrome. Values within the normal range may occur in the face of active myositis in these illnesses. Findings of a low serum CPK values may occur in the absence of steroid treatment. Thus, a low serum CPK value is frequently found in patients with connective tissue diseases and a normal value should not dissuade one from the diagnosis of myositis.