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Biomedical subjects

J Kekow

Publications and source records attributed to J Kekow.

At least 55 records · Page 3Linked to original sources
PubMed1991

[Modulation of immunocompetent cells in the synovial fluid TGF-beta].

Mononuclear cells (MNC) in synovial fluids from patients with rheumatoid arthritis and other arthropathies differ clearly from MNC in peripheral blood. Typically the ratio of CD4(+)-/CD8+ lymphocytes is inverted and the response to mitogens/cytokines (IL-1/IL-2) is impaired. Active TGF-beta (transforming growth factor beta) was found to account for these abnormalities, and the major isoform was identified as TGF-beta 2.

Arthritis, Rheumatoid↗
PubMed1990

Transforming growth factor-beta and cellular immune responses in synovial fluids.

Mononuclear cells in synovial fluids (SF) from patients with rheumatoid arthritis and other arthropathies are characterized by functional and phenotypic changes, including impaired mitogen responsiveness and inverted ratios of CD4+/CD8+ T lymphocytes. This is related to previously described activities in synovial fluids that inhibit proliferation of lymphocytes induced by mitogens and cytokines. The present study examines the relationship of these activities and transforming growth factor beta (TGF-beta), which is now known as the most potent endogenous inhibitor of lymphocyte function. It is shown that most of the activity in SF that inhibits IL-1-induced thymocyte or T cell proliferation is neutralized by a specific antibody to TGF-beta. Analysis of the SF in the CCL64 assay, a standard test for TGF-beta, showed a close correlation between the levels of immunosuppressive activity and TGF-beta. SF contain spontaneously active inhibitors of T cell function and this is caused by the presence of active TGF-beta. Higher titers are found after transient acidification, which is known to activate the latent form of TGF-beta. Characterization of the TGF-beta isoforms showed that most of the material in SF is TGF-beta 2. Analysis of TGF-beta effects on T cell subsets demonstrated that it completely inhibits proliferation of CD4+ cells whereas at the same concentrations of purified or rTGF-beta CD8+ cells are only inhibited by maximally 31.1%. SF also preferentially inhibit CD4+ Th cell proliferation and this effect is neutralized by antibody to TGF-beta. Collectively these results indicate that the presence of TGF-beta accounts for most of the immunosuppressive activities in SF and that this factor may be responsible for functional and phenotypic changes of SF lymphocytes.

Arthritis, Rheumatoid↗
PubMed1990

Transforming growth factor beta and noncytopathic mechanisms of immunodeficiency in human immunodeficiency virus infection.

This study examines the contribution of transforming growth factor beta (TGF beta), one of the most potent endogenous immunosuppressive factors, to the development of immunodeficiency in human immunodeficiency virus (HIV) infection. Increased titers of TGF beta were found in supernatants of peripheral blood mononuclear cells (PBMCs) from HIV-infected donors as compared to uninfected controls (P less than 0.001). This correlated closely with defective responses of CD4+ lymphocytes to the recall antigens tuberculin purified protein derivative or tetanus toxoid. The addition of TGF beta-neutralizing antibody to PBMCs partially restored these defective T-cell responses. Furthermore, purified TGF beta or HIV+ PBMC culture supernatants preferentially inhibited proliferation of CD4+ lymphocytes as compared to CD8+ cells. The increased expression of the TGF beta protein was associated with increased TGF beta mRNA as determined by a polymerase chain reaction assay. This increase in TGF beta protein and mRNA was due to a selective upregulation of the TGF beta 1 isoform. These results indicate that overexpression of TGF beta 1 occurs in HIV-infected individuals and that this cytokine can contribute to impaired immune functions and to depletion of CD4+ T lymphocytes.

Acquired Immunodeficiency Syndrome↗
PubMed1989

[Polyclonal B-cell activation by so-called immunopotentiation (immunostimulants)].

Immuno-augmentation with substances of bacterial origin was studied in vitro for its ability to induce polyclonal B-cell activation. Biostim, Broncho-Vaxom, Omnadin, Paspat and OK 432 were compared for their B-cell mitogenicity with classical polyclonal B-cell activators (Staph. aureus Cowan I, KlebsM, Pokeweed mitogen). B-cell mitogenicity, as measured by 3H-thymidine incorporation into proliferating blood B-cells, was not induced by any of the studied preparations. On the other hand, OK 432 produced a T-cell dependent and Biostim a T-cell independent blood B-cell differentiation in immunoglobulin producing cells. However, the extent of immunoglobulin production was clearly less than with the polyclonal B-cell activator KlebsM. These results demonstrate that, in some of the preparations, in vivo polyclonal B-cell activation can be expected to occur.

Adjuvants, Immunologic↗
PubMed1988

[Anticytoplasmic antibodies as serological markers and activity parameters of Wegener's granulomatosis. A prospective study].

Sera from 105 patients with Wegener's granulomatosis (WG) and 1,500 control subjects (with, among other diseases, primary or secondary vasculitis, collagen disease, glomerulonephritis or various granulomas) were examined with respect to sensitivity, specificity and importance of anticytoplasmic antibodies (ACPA) as markers of disease activity. The antibodies were demonstrated in 77 of the 105 patients (73%) with WG and six of the controls (less than 1%). They were always present in active WG (57 patients). In a prospective study of 21 closely followed patients with WG there was a close correlation between ACPA titre and the disease activity as measured by clinical and biochemical criteria. After induction of remission there was in all instances a clear fall in titre, while the titre rose again on exacerbation but remained unchanged during superinfection. Thus anticytoplasmic antibodies are useful both in primary diagnosis and in estimating disease activity of WG.

Adolescent↗
PubMed1988

Measurement of rat insulin. Enzyme-linked immunosorbent assay with increased sensitivity, high accuracy, and greater practicability than established radioimmunoassay.

Total immunoreactive insulin (IRI) is conventionally determined by radioimmunoassays. IRI measurement in rats can be made more sensitive, accurate, and practical, as demonstrated by a new modified enzyme-linked immunosorbent assay (ELISA). It is characterized by indirect binding of an anti-insulin antibody by an antiglobulin antibody and uses the principle of competitive saturation. In this ELISA, IRI can be determined in a wide range of concentrations, corresponding to the standards. The standard curve ranges from 100 to 0.049 ng/ml IRI (1 ng/ml approximately 23.4 microU/ml approximately 172 pM rat insulin). The statistical analysis shows between- and within-assay coefficients of variation of less than or equal to 15%.

Animals↗
PubMed1988

Predominance of the IgG1 subclass in the hypergammaglobulinemia observed in pre-AIDS and AIDS.

In addition to the well-known T-cell dysfunctions in AIDS, hypergammaglobulinemia, mostly IgG, and autoimmune phenomena indicate that B cells are also involved. Reports of HIV-infected and activated B cells suggest T cell-independent B-cell abnormalities. In order to assess the IgG subclasses involved in hypergammaglobulinemia, we examined all four IgG subclasses in sera and in vitro with an enzyme-linked immunosorbent assay (ELISA). The in vitro studies included 7-day cultures of mononuclear cells and highly purified B cells stimulated with a T cell-independent polyclonal B-cell activator (Klebsiella pneumoniae, KlebsM). Cultures were done with cells from seven patients with AIDS, seven patients with persistent generalized lymph node enlargement and HIV antibodies, and normal controls. In vivo, hypergammaglobulinemia was found to be restricted to the IgG1 subclass. In vitro, high spontaneous levels of IgG were not elevated significantly under stimulatory conditions, as demonstrated by the measurement of all four IgG subclasses in the culture supernatants. In vitro, hypergammaglobulinemia also resulted from IgG1. These results indicate that there are B-cell abnormalities in pre-AIDS and AIDS, in that the B-cell preactivation in vivo resulting in hypergammaglobulinemia is restricted to IgG1.

AIDS-Related Complex↗
PubMed1988

The in vitro influence of rIL2 on the B-cell dysfunction in patients with persistent generalized lymph node enlargement (PGL) or AIDS.

In AIDS elevated serum Ig levels and autoimmune phenomena indicate that B cells are also involved. The human immunodeficiency virus (HIV) can be cultivated in B cells, and HIV can stimulate B cells. In order to characterize the B-cell dysfunction and conditions for modulating it, functional studies with highly purified B cells were done in four patients with PGL and HIV-positive sera. Data were compared with those from patients with AIDS and normal controls. The experiments consisted of an in vitro study of the differentiation response (IgM/G secretion into culture supernatants) to a T cell-independent polyclonal B-cell activator (PBA) [Klebsiella pneumoniae, KlebsM]. A weak increase in IgM/G levels under stimulatory conditions was characteristic. Addition of recombinant interleukin 2 (rIL2) failed to increase the spontaneous Ig levels. However, coculture experiments using KlebsM and rIL2 resulted in Ig levels like those known from healthy individuals. Patients with frank AIDS did not respond with increased IgG secretion. This indicates that the abnormal B-cell differentiation response to PBAs can be modulated by rIL2 in patients with PGL and partly in AIDS (only IgM).

Acquired Immunodeficiency Syndrome↗
PubMed1987

Influence of factor substitution on the B-cell response in hemophiliacs.

Studies in hemophiliacs receiving factor concentrates demonstrated T-cell defects in vitro. Recently, B-cell dysfunctions were described in AIDS and pre-AIDS and in some hemophiliacs. To investigate the B-cell function in hemophiliacs in relation to factor substitution, we examined five patients with mild (substitution less than 20,000 U/year) and seven with severe (greater than 100,000 U/year) hemophilia A and compared the data with normal control individuals. The B-cell proliferative response (3H-thymidine uptake) to Staphylococcus aureus Cowan I and the differentiation response (Ig secretion into culture supernatants) to T-cell-dependent or -independent polyclonal B-cell activators (PBAs) were studied in vitro. In contrast to T-cell dysfunctions, which correlate with the amount of clotting factor concentrates, the B-cell proliferative response was not affected. Stimulation with PBAs however failed to increase elevated spontaneous IgG levels and showed a diminished increase in IgM levels in severe, but not in mild, hemophilia. Our data give evidence of a T-cell-independent B-cell dysfunction in asymptomatic hemophiliacs that correlates with factor substitution.

Antibody Formation↗
PubMed1987

B-cell reactivity in homosexuals with persistent generalized lymphadenopathy (PGL).

In addition to the well known T-cell dysfunctions in AIDS, hypergammaglobulinaemia and autoimmune phenomena indicate an involvement of the B cell as well. Reports of HTLV-III/LAV-infected B cells suggest T-cell-independent B-cell abnormalities. To look for early B-cell dysfunctions, we examined a high-risk group of AIDS consisting of six homosexuals with PGL and HTLV-III/LAV antibodies, comparing these data to those of patients with AIDS/ARC and a normal control. In vitro studies included the B-cell proliferation response (3H-thymidine uptake) to Staphylococcus aureus Cowan I and the differentiation response (Ig secretion into culture supernatants) to T-cell-dependent/-independent polyclonal B-cell activators (PBAs). Profound alterations were found in both the proliferation and the differentiation responses. The weak response even to T-cell-independent PBAs indicates a B-cell dysfunction that is not due only to a T-cell defect in patients with PGL, similar to that observed in AIDS.

AIDS-Related Complex↗
PubMed1986

Impaired T-cell-independent B-cell maturation in systemic lupus erythematosus: coculture experiments in monozygotic twins concordant for Klinefelter's syndrome but discordant for systemic lupus erythematosus.

In a case of monozygotic twins discordant for systemic lupus erythematosus (SLE), coculture experiments with isologous (i.e., genetically identical) lymphocytes were performed. Adequate T-helper-cell function in the SLE twin was demonstrated. Lack of B-cell responsiveness to T-cell-dependent and T-cell-independent polyclonal activators points to a T-cell-independent B-cell maturation defect in the SLE twin.

Adolescent↗
PubMed1986

Abnormal B-cell response to T-cell-independent polyclonal B-cell activators in homosexuals presenting persistent generalized lymph node enlargement and HTLV-III antibodies.

B-cell functions were investigated in a well-defined high-risk group for the development of AIDS/AIDS-related complex (ARC). Stimulation of mononuclear cells (MNC) with T-cell-independent polyclonal B-cell activators failed to increase high spontaneous IgG levels observed in vivo and in vitro. The secretion of IgM following stimulation with Klebsiella M (Klebs M) or Salmonella (Salm) membrane preparation increased by a factor of 4 to 6 and thus ranged between the results of the control group and those of AIDS/ARC patients; the response to a T-cell-independent B-cell mitogen, Staphylococcus aureus Cowan I (SAC), showed profound abnormalities as well in this group. This indicates that functional B-cell abnormalities can be seen in addition to T-cell dysfunctions in patients at increased risk for the development of AIDS/ARC.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Abnormal B cell response to T cell-independent polyclonal B cell activators in haemophilia A.

In addition to T cell abnormalities, patients with haemophilia A show a separate B cell dysfunction. Characteristic are elevated spontaneous IgG (not IgM) levels in the patient's sera and in the culture supernatants of peripheral blood mononuclear cells. It is also observed that these cells fail to show a differentiation response to T cell-independent B cell activators. The B cell dysfunction correlates with the amount of factor VIII concentrates given prophylactically to patients with severe haemophilia. In contrast to the acquired immune deficiency syndrome (AIDS), the proliferation response to B cell mitogens is not affected.

Adolescent↗
PubMed1985

[T and B cell reactions in AIDS and AIDS risk groups].

In addition to T-cell defects AIDS shows a separate B-cell dysfunction. Elevated spontaneous IgG-levels (not IgM) and a lacking proliferative and differentiation response to polyclonal B-cell activators can be demonstrated in vitro.

Acquired Immunodeficiency Syndrome↗