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Biomedical subjects

H H Fudenberg

Publications and source records attributed to H H Fudenberg.

At least 19 recordsLinked to original sources
PubMed1989

Increase of immunoglobulin G3 subclass is related to brain autoantibody in Alzheimer's disease but not in Down's syndrome.

The proportions of IgG subclasses (G1, G2, G3 and G4) were quantified in sera from Alzheimer's disease (AD) patients, older Down's syndrome (DS) patients and age-matched controls. The levels of IgG1, IgG2 and IgG4 were normal in AD patients, but the proportions of IgG3 were significantly elevated in 9 of 20 (45%) patients (0.803 +/- 0.141 mg/ml; p less than 0.001) compared to the level found in age-matched controls (0.471 +/- 0.161 mg/ml; n = 10). The IgG3 level in the remaining 11 AD patients was slightly lower than the controls (0.385 +/- 0.104 vs. 0.471 +/- 0.161 mg/ml), but it did not reach statistical significance (p = 0.149). In contrast, patients with DS displayed imbalance of IgG2, IgG3, and IgG4 subclasses; they had significantly increased IgG3 but decreased IgG2 and IgG4 levels. The IgG1 level was within normal range. Moreover, a majority of AD sera (8 of 9) with elevated IgG3 concentration were positive for brain autoantibody. The remaining 11 AD sera without elevated IgG3 level, all DS sera and all control sera were negative for brain autoantibody. This finding indirectly suggests that brain autoantibody is mainly due to IgG3 subclass, at least in one subset of AD patients.

Adult↗
PubMed1988

Binding of [125I]corticotropin releasing factor to blood immunocytes and its reduction in Alzheimer's disease.

The binding of [125I]iodine-labelled corticotropin releasing factor (CRF) was studied using peripheral blood lymphocytes from normal donors and Alzheimer's disease (AD) patients. The high affinity binding of [125I]CRF was found in the membranes of various immunocytes. Monocytes and T cells displayed binding which was several times greater than the binding of brain (cortical) cells. The immunocyte CRF binding was significantly (P less than 0.001) lower in 14 out of 18 (78%) AD patients relative to non-AD controls, suggesting the association of CRF in the pathology of AD. Our data demonstrate that blood immunocytes can be used to analyze deficiency of neurohormone sites in neuropsychiatric diseases, e.g., AD.

Adult↗
PubMed1987

An animal model for evaluation of antigen-specific dialyzable leukocyte extracts therapy of osteosarcoma.

The effects of human osteosarcoma (OS)-specific dialyzable leukocyte extracts (DLE) in hamsters bearing human OS were investigated. The DLE used in this investigation was prepared from rabbits immunized with human osteosarcoma-associated antigens (DLE-OSAA). Tuberculin (DLE-PPD) and control DLE were prepared from rabbits injected with tuberculin or 0.85% NaCl (DLE-NaCl). DLE was administered subcutaneously into inbred hamsters (each injection contained DLE derived from 10(7) rabbit leukocytes). Four groups of animals were studied: group 1, amputation alone; group 2, amputation plus DLE-OSAA; group 3, amputation plus DLE-PPD; group 4, amputation plus DLE-NaCl. Of the DLE-OSAA-treated animals (group 2), 60% were still alive at 300 days postamputation; whereas in animals in groups 1, 3, and 4, all died within 90 days postamputation. In separate experiments, we found that 100% of the animals in groups 1, 3, and 4 developed pulmonary metastases within 30-60 days postamputation, whereas only 20% of the animals in group 2 developed metastases at the same time; indeed 40% of the DLE-OSAA-treated animals were free of metastases in 240-300 days postamputation. Both the leukocyte adherence inhibition assay (LAI) and lymphocyte DNA synthesis assay (LDS) were used to monitor the transfer of antigen-specific cell-mediated immunity in each group of tumor-bearing hamsters. All surviving hamsters in group 2 had high LAI and LDS activity. Our results suggest that DLE-OSAA is effective in preventing pulmonary metastases and death of OS-bearing hamsters (after amputation) as compared with amputation alone, amputation plus DLE-NaCl, and amputation plus DLE-PPD, and that its effect is via an antigen-specific mechanism.

Animals↗
PubMed1987

Alpha 1-acid glycoprotein (alpha 1-AGP) on the membrane of human lymphocytes: possible involvement in cellular activation.

A glycoprotein termed alpha 1-acid glycoprotein (alpha 1-AGP) is a component of normal human serum; its concentration is often increased in several pathological disorders, including acute inflammation and cancer. Inhibitory effects of alpha 1-AGP on some in vitro T and B cell function assays have been reported but our recent data indicated that alpha 1-AGP is indeed a T cell mitogen at physiological concentrations. The present study was designed to investigate: (a) the relationship between this glycoprotein and two other glycoproteins of the T and B cell membrane, i.e. the T3 and Ia antigens; (b) the ability of lymphocytes to take up exogenous alpha 1-AGP; (c) the different expression of alpha 1-AGP on the T cell membrane upon different activation pathways, i.e., autologous non-T-cells (B cells and monocytes) phytohemagglutinin and anti-T3 monoclonal antibody (MAb) stimulations. The data reported herein show no competition at the membrane level between anti-alpha 1-AGP and anti-T3 or anti-Ia MAbs. In addition, (1) the lymphocytes were able to absorb alpha 1-AGP from the culture medium and (2) the expression of this glycoprotein was enhanced upon T cell stimulation (all three stimulants employed induced an increase of alpha 1-AGP positive T cells), thus suggesting a possible role of this glycoprotein in in vitro T cell activation.

Adult↗
PubMed1987

Generation of phenotypically distinct macrophage-hepatoma hybrid clones.

By fusion of C3H/HeJ splenic adherent mononuclear cells enriched for macrophages with HPRT-deficient C57L/J HH- hepatoma cells, we have generated six macrophage-hepatoma hybrid clones. The hybrid nature of isolated clones was demonstrated by karyotypic analysis. The hybrid clones were screened for macrophage properties by assaying the presence of two enzymes: nonspecific esterase and lysozyme. Three of six hybrids expressed higher amount of Ia antigen and less amount of FcR; the other three hybrids expressed higher amounts of Fcr, but no Ia antigen. Phagocytosis of serum-opsonized beads is positively correlated with FcR expression, while the proliferation of antigen-primed lymphocytes is only induced by antigen-pulsed hybrids expressing Ia antigen. One hybrid clone (MH3-1) secreted significantly higher level of PGE2 and also expressed Ia antigen with higher ability of antigen-presentation. The data suggest that the cell hybridization can segregate macrophage-featured phenotypes into different hybrid clones which perform distinct functions. It may facilitate the study on the relationship of macrophage functions and the relationship between the functions and defined cell structure.

Animals↗
PubMed1987

T cell activation surface markers and autologous mixed lymphocyte reaction do not differ in true and pseudo food allergy.

Eighteen patients affected by itching, urticaria, eczema, angioedema, and asthma related to food-stuff intake were studied and classified in two groups (true food allergy and pseudoallergy) on the basis of clinical data, skin prick tests, total and specific IgE levels (PRIST and RAST) and double-blind challenge test. Autologous mixed lymphocyte reaction (AMLR) and T cell activation markers were thought to be tests possibly useful to discriminate between 'true' food allergy and 'pseudoallergy'. The present study failed to show either a significant increase in T cell activation markers (MLR4, Ia) or a significant decrease in AMLR proliferation in such subjects as compared to normal controls. In addition, we found no differences between 'true' allergic and 'pseudoallergic' patients on the basis of the parameters evaluated. Although the AMLR defect was reported both in asthma and in dermatitis, and therefore was thought to be related to atopy, the present data do not confirm this hypothesis in 'true' food allergy.

Adult↗
PubMed1986

Lymphocyte stimulation in vitro by orosomucoid glycoprotein.

Mitogenesis of human peripheral blood lymphocytes as measured by the uptake of [3H]thymidine was stimulated in vitro by pure orosomucoid glycoprotein when used at concentrations that are considerably lower than the physiological plasma level. The lymphocyte cultures stimulated with PHA or PWM were not affected by low concentration (67 micrograms/ml), but they were mildly suppressed by high concentration (1 mg/ml) of this glycoprotein. The stimulatory response was relatively greater with fractionated T cells than the non-T cells (B cells and monocytes). At 50 micrograms/ml concentration of orosomucoid, the lymphocyte activation was found in randomly selected blood donors which included normal healthy volunteers and patients with T cell immunodeficiency or Alzheimer's disease, demonstrating a consistent immunostimulatory action of this glycoprotein.

Alzheimer Disease↗
PubMed1986

Inhibitory effect of an antibody against alpha 1-acid glycoprotein (alpha 1-AGP) on autologous mixed lymphocyte reaction and anti-T3 T-lymphocyte activation.

The action of an anti-alpha 1-AGP antibody on AMLR, anti-T3 and PHA T-lymphocyte proliferative response was evaluated. We observed a strong dose-dependent inhibition on T-lymphocyte proliferative responsiveness to autologous non-T cells and to anti-T3 stimulus, whereas PHA activation was unaffected. A lower degree of inhibition of the proliferative response was also observed on pretreating both T and non-T cells with the antibody; the addition of anti-alpha 1-AGP in the culture containing cells pretreated with the antibody showed a further inhibition of thymidine incorporation. The data suggest a direct influence of the antibody on membrane alpha 1-AGP and support a positive role of this glycoprotein (distinct from Ia and T3 antigens) on both anti-T3 and autologous non-T cell T-lymphocyte responsiveness, thus indicating the involvement of alpha 1-AGP in the T3-Ti antigen-specific pathway of T-cell activation.

Adult↗
PubMed1986

Does normal lymphocyte DNA synthesis in response to PHA exclude cell-mediated immunodepression?

PHA stimulation assay was the first in vitro method for evaluating the T-cell function, and this T-cell proliferative response has been routinely used to discriminate between normal subjects and patients with deficiency in cell-mediated immunity. However, [3H]thymidine incorporation into lymphocyte DNA can be studied by using additional in vitro assay methods since they measure different lymphocyte activation pathways. In the present study we selected three different tests to investigate the reliability of this single approach: PHA induced lymphocyte DNA synthesis; T lymphocyte DNA synthesis to anti-T3 monoclonal antibody (OKT3); autologous mixed lymphocyte reaction (AMLR). In addition, IL-2 receptor expression on the membrane of T-cell stimulated in AMLR both with PHA and anti-T3 was evaluated. This study was performed in various groups of subjects: normal young controls, aged healthy individuals, and patients with Alzheimer's disease (AD), Retinitis Pigmentosa (RP), and with cell-mediated immunodeficiency and clinical evidence of recurrent viral infections (ID). The data reported herein show heterogeneity of results in each group studied and demonstrate the necessity of employing more than one laboratory test for the routine evaluation of T-cell-mediated immunity.

Alzheimer Disease↗
PubMed1986

Evidence of T-lymphocyte functional impairment in Huntington's disease.

Huntington's Disease (HD) is a degenerative neurological disorder with autosomal dominant transmission. Although immunological defect(s) have been postulated, no confirmed laboratory evidence for this exists. In the present study we observed activated T cells in the peripheral blood of HD patients (using 4F2 monoclonal antibody), whereas the percentage of T cells bearing T-cell activation markers such as HLA-DR and MLR4 antigens was normal. We then studied T cells of HD patients in some functional assays. Since it has been suggested that autologous mixed lymphocyte reaction (AMLR) includes several immune mechanisms in which distinct cell subsets interact and perform distinct regulatory functions, it is conceivable that the remarkable deficiency of AMLR herein observed in HD patients results from some abnormal immune regulation which may contribute to the pathology of this condition. Additional experiments demonstrated a defect of AMLR in three asymptomatic young sibs of HD patients, and coculture experiments between T cells of patients (as responders) and non-T cells of their sibs (as stimulators), and vice versa, produced no proliferative response. Subnormal responsiveness in allogeneic MLR was also observed. Normal or enhanced PHA-induced production of both IL-2 and IFN-gamma in vitro was detected. These experimental data suggest a cellular branch of the immune system in HD; however, they do not indicate if this defect is primary or secondary to the disease itself.

Adult↗
PubMed1986

Detection of brain autoantibodies in the serum of patients with Alzheimer's disease but not Down's syndrome.

The immunofluorescent staining of antibodies specifically binding to rat brain tissue sections was investigated in 95 human sera including 30 cases of Alzheimer's disease. A high incidence of specific antibrain antibody was found among Alzheimer's patients (57% positive) compared to other neurological disease controls (only 8% positive) or normal young and aged healthy controls (none positive).

Adolescent↗