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Biomedical subjects

H H Fudenberg

Publications and source records attributed to H H Fudenberg.

At least 55 records · Page 3Linked to original sources

Partial purification and characterization of B cell growth factor constitutively secreted by human T-cell hybridoma.

Human T cell hybridomas were established by fusion of PHA-activated PBL with the 8-azaguanine resistant human T-leukemic cell line CEM-CM3. High levels of B cell growth factor (BCGF) activity were detected in the supernatants of hybridoma C8-2B2 and its subclones. Hybridoma C8-2B2, in addition to the Leu 3a, also expressed the OKT11 surface marker which was not detectable on the parent CEM-CM3 cells. BCGF from the culture supernatant was purified by combined use of salt fractionation and gel filtration to 36.6 fold with 23.9% recovery of activity. The BCGF produced by hybridoma C8-2B2 has a molecular weight range of 16,000-20,000 in two major electrophoretically different forms with pI values of 6.4 and 7.4.

Antigens, Differentiation, T-Lymphocyte↗

In vitro restoration of immune responses in aging humans by isoprinosine.

The in vitro effects of isoprinosine (ISO) on the immune responses of aging humans were investigated. 64 healthy elderly humans (65 yr of age or over) were included in this study. Four immune parameters were measured, namely, Concanavalin A (ConA)-induced lymphocyte proliferation, natural killer cell (NK) activity, neutrophil chemotaxis, and interleukin-2 (IL-2) production. The ConA-induced lymphocyte proliferation was depressed in 55 of the 64 individuals (85.9%%), while the NK activity was depressed in 41 of the 64 individuals (64%). Neutrophil chemotaxis was depressed in 52 of the 64 individuals (81.1%) and IL-2 production was depressed in 35 of the 64 individuals (54.6%). In the presence of ISO, ConA-induced lymphocyte proliferation, NK activity, neutrophil chemotaxis, and IL-2 production were restored to normal or near normal levels in 50 of the 55 (90.0%), 35 of the 41 (85.3%), 44 of the 52 (84.6%), and 25 of the 35 (71.4%) aging humans, respectively. Our results indicate that ISO acts as an immune potentiator in these in vitro immune assays.

Adult↗

Partial restoration of impaired interleukin-2 production and Tac antigen (putative interleukin-2 receptor) expression in patients with acquired immune deficiency syndrome by isoprinosine treatment in vitro.

The in vitro effects of isoprinosine (ISO) on interleukin-2 (IL-2) production, the expression of Tac antigen (IL-2 receptor) on lymphocytes, and the ability of Leu 3(+) cells to absorb interleukin-1 (IL-1) were investigated in 10 patients with acquired immune deficiency syndrome (AIDS). In 9 of the 10 patients, production of IL-2 from mononuclear cells and Leu 3(+) cells was depressed; expression of Tac antigen on mononuclear cells and Leu 2(+) cells was found to be depressed in 9 of 10 patients. The ability of the Leu 3(+) lymphocytes to absorb IL-1 was depressed in all (four of four) patients studied. After ISO treatment, IL-2 production, Tac antigen expression and IL-1 absorption were restored to normal or near normal levels in most of the patients. These results suggest that ISO has an immunostimulating capacity in AIDS patients and that the potential of ISO in immune response restoration in AIDS patients deserves critical consideration.

Acquired Immunodeficiency Syndrome↗

Anticentromere antibody and immunoglobulin allotypes in scleroderma.

Fifty-five unrelated whites with disorders in the scleroderma spectrum who had both antinuclear antibodies and Raynaud's phenomenon (RP) were studied. Of the 22 patients with anticentromere antibody (ACA), three had diffuse scleroderma; 16 had the complete or incomplete syndrome of calcinosis, RP, esophageal dysmotility, sclerodactyly, and telangiectasia (CREST syndrome); and three had RP only. Thirty-three patients with other nuclear patterns all had systemic scleroderma (28 diffuse scleroderma, five CREST syndrome). Patients with ACA had less organ system involvement, and lower frequencies of anemia and elevation of sedimentation rate than ACA-negative patients, but these differences were not statistically significant. They also had fewer manifestations of CREST syndrome. All 55 patients were studied for the Gm and Km allotypic markers. No association was found between Gm or Km allotypic markers and scleroderma or between the allotypic markers and the presence of ACA.

Adolescent↗

Immunoglobulin allotypes and the immune response to wheat gliadin in a Finnish population with celiac disease.

Several immunoglobulin allotypes were determined for 42 Finnish children with celiac disease (CD) and for 42 normal controls. The CD patients had been previously HLA typed; all but 2 were positive for HLA B8, DR3 or both. The incidence of HLA B8, DR3 and DR7 was found to be significantly higher in patients than in a control group. No significant association was found between any of the immunoglobulin allotypes and CD either when patients were grouped as a whole or when grouped according to sex. In addition, no association was found between levels of antigliadin antibody and the G2m(23) allotypic marker. This latter finding is in sharp contrast with the report of a significant association in American Caucasians between G2m(23) and the level of antigliadin antibodies by Weiss et al. [J. clin. Invest. 72: 96-101, 1983].

Adolescent↗

Effects of long-term treatment of mice with anti-I-J monoclonal antibody and dialyzable leukocyte extract on immune function and lifespan.

In 1969 Walford hypothesized that age-related dysfunctions of the immune system may be involved in the pathogenesis of the lesions and disease of aging. Studies were initiated to test whether immunologic interventions intended to maintain the integrity of the immune system would delay the onset of diseases of aging and prolong lifespan. Adult BC3F1 mice were treated with anti-I-J monoclonal antibody, with human dialyzable leukocyte extract, or with saline once a week for one year. Spleen cells from the mice were then assayed for suppressor, T-helper and B-cell activity. Treatment with dialyzable leukocyte extract decreased the elevated nonspecific suppressor activity. Mice treated with anti-I-J antibody had elevated T-helper cell activity. In another experiment, mice were treated weekly with anti-I-J antibody, dialyzable leukocyte extract, or saline from 18 months of age until natural death. The mice were immunized with avian gammaglobulin at 27 and again at 29 months of age. Both types of immunologic intervention resulted in a greater secondary antibody response than that of the saline-treated control mice. Mice treated with anti-I-J antibody survived longer than did mice of the other two groups. There was a correlation between the magnitude of the secondary response of individual mice and their lifespan. The results provide support for the immunologic theory of aging.

Aging↗

Phencyclidine-induced immunodepression.

Phencyclidine ("PCP" or "angel dust") and some of its derivatives are psychotomimetic drugs that have been used in general anesthesia for some time. This drug blocks potassium ion channels in brain tissue, and there is a specific PCP binding to lymphocytes. In a study of the effects of this drug on immunocyte function, it was found that humoral and cellular immune responses in vitro were depressed when immunocytes were treated with PCP before biological assay. This finding has implications for PCP abuse and also for the use of its derivative in general anesthesia, where it may contribute to postoperative infection.

B-Lymphocytes↗

The role of PNP enzyme in autologous rosette-forming cells.

Since purine nucleoside phosphorylase has been associated with suppressor function in lymphocytes, enzyme activities were studied in autologous rosette-forming cells, a subset showing suppressor properties. Levels of this enzyme were higher in these cells than in other T cells. Con A induction of autologous red cell receptors and suppressor activity of T cells were both inhibited in dose-dependent fashion by Formycin B, a well known inhibitor of purine nucleoside phosphorylase. Inhibition of autologous rosette-forming cells was obtained after pulse treatment of cells with Formycin B for as little as 1 hr, whereas cell proliferation was only inhibited when Formycin B was present throughout culture; this confirms the independence of cell proliferation, and development of red cell receptors and suppressor activity. This study indicates a crucial role for purine nucleoside phosphorylase enzyme in induction of T cell suppressor activity.

Concanavalin A↗

One subset of patients with retinitis pigmentosa has immunologic defects.

Immunological evaluation of 20 patients with retinitis pigmentosa (RP) revealed significantly diminished circulating T-lymphocyte numbers and function and a high frequency of serum antibodies to human IgG in comparison with a healthy matched control population. However, these differences were due to severely abnormal results found in one subpopulation within the total patient group; this dichotomy was unrelated to the mode of inheritance or clinical severity of RP in individual patients. Thus, RP appears to be a syndrome rather than a disease and includes a form characterized by defective immunity. Whether this is involved in the pathogenesis of the retinal degenerative process is conjectural.

Antibodies, Anti-Idiotypic↗

Production of antibody to human osteosarcoma associated antigens by continuous human lymphoblastoid cell lines.

Human lymphoblastoid cell lines that produce specific antibody against human osteosarcoma associated plasma membrane antigens have been established by preselecting OSAA binding human B lymphocytes from an osteosarcoma patient followed by Epstein-Barr virus (EBV) transformation. Four cell lines ( Kla -1, Kla -2, Kla -3, Kla -4) were obtained and cloned. The antibodies were lambda light containing IgM. The specificities of the antibodies were confirmed by immunofluorescence assays using tumor cell lines of various histologic types. Positive immunofluorescence was observed with all human osteosarcoma cell lines tested except one but not with tumor cell lines of other histologic types.

Antibodies, Neoplasm↗

Role of autorosette forming cells in antibody synthesis in vitro: suppressive activity of ARFC in humoral immune response.

The role of autologous rosette forming cells (ARFC) in humoral immune responses was studied using an in vitro system. While depletion of ARFCs from PBL resulted in a significant increase of either total IgG or anti-TT IgG, addition of these cells to the system decreased the production of immunoglobulin to a level comparable to that of unfractionated PBL. The majority of the ARFCs reacted with anti-Leu2a and anti-Leu8. In contrast, the majority of non-ARFCs reacted with Leu3a and only 10% with Leu8 monoclonal antibodies. Stimulation of unfractionated PBL with concanavalin A (ConA) resulted in an increase of the ARFC population. ConA stimulation also increased the number of cells reactive with anti-Leu2 and/or anti-Leu8. The autorosette population had a higher purine nucleoside phosphorylase (PNP) content than the non-ARFC population. Although the ARFC suppressed synthesis of antibody by B cell in vitro when they were mixed with either autologous or allogeneic B cells, a marked proliferation of non-B cells was evident. We conclude that at least two different subpopulations of T cells are capable of forming rosettes with autologous red blood cells.

Antibodies, Monoclonal↗

An open-label trial of immunomodulation therapy with inosiplex (Isoprinosine) in patients with alopecia totalis and cell-mediated immunodeficiency.

Nine patients with alopecia totalis and associated defects in T lymphocyte function were admitted to an open-label trial of inosiplex therapy. All nine developed enhanced T cell function and seven had clinically significant hair regrowth. The immunologic response to inosiplex was dose-dependent in five patients. These data provide new information on the in vivo effects of inosiplex on the human immune system and support the hypothesis that disturbances of immunologic mechanisms may play a pathogenetic role in alopecia totalis in certain patients.

Adjuvants, Immunologic↗

Immunological profiles in alopecia areata.

Cell-mediated immunity and auto-immune phenomena were investigated in sixty patients with active alopecia areata of various degrees of severity. Serum auto-antibodies to thyroid antigens were detected in twenty-three patients. Examination of T-lymphocyte populations, lymphocyte DNA synthesis, and lymphokine production in response to mitogen stimulation revealed no differences between the sixty patients and matched healthy control subjects. However, patients with thyroid auto-immunity and/or the presence of alopecia totalis or universalis showed significant reductions in interactive T lymphocytes (recognized by rosette formation with human B lymphoblastoid cells) and diminished production of leukocyte migration inhibition factor in response to stimulation with phytohaemagglutinin. This suggests that immune mechanisms may be involved in the pathogenesis of alopecia areata which is associated with thyroid auto-immunity or which progresses to total hair loss.

Adolescent↗

Functional heterogeneity of human cord blood monocytes.

Human cord blood monocytes were separated into four different subpopulations by means of a discontinuous bovine serum albumin (BSA) gradient. Of the least dense, 31% were present in fraction A, 17% in fraction B and 13% in fraction C and of the most dense, 20% were in fraction D. The rest (17%) sedimented as a pellet, of which 93% were dead cells. The monocytes of fraction C (density greater than or equal to 1.070) demonstrated suppressor activity on in vitro antibody synthesis of maternal B cells. Fraction D (density greater than or equal to 1.075) monocytes enhanced antibody synthesis of maternal B cells compared with synthesis produced in a similar experiment with unfractionated monocytes. Addition of either fraction A or B monocytes to the mixed culture of T and B cells resulted in antibody production comparable to that produced by addition of unfractionated monocytes. The functional heterogeneity of the cord monocytes was assayed also by 2-deoxyglucose (2-DOG) uptake, a marker for immunological macrophage activation. Fractions A and D showed significantly higher 2-DOG transport than that of unfractionated monocytes; in contrast, fraction C showed a 50% reduction of 2-DOG uptake. Furthermore, in contrast to fraction D, fraction C possessed only minimal phagocytic activity (for antibody-coated sheep erythrocytes) and minimal hemoxygenase enzyme activity. These data demonstrate functional heterogeneity of cord blood monocytes.

Antibody Formation↗