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Biomedical subjects

H H Fudenberg

Publications and source records attributed to H H Fudenberg.

At least 73 records · Page 4Linked to original sources
PubMed1984

Two unlinked genetic loci interact to control the human immune response to type III group B streptococcal antigen.

Serum samples were collected from 30 healthy adult Caucasian volunteers before and after immunization with native type III polysaccharide of group B streptococcus. Serum antibody to this polysaccharide was measured and sera were typed for several Gm and Km(1) allotypes. A significant interactive effect of Gm(23) and Km(1) was found on immune responsiveness to native type III group B streptococcus polysaccharide antigen.

Antigens, Bacterial↗
PubMed1984

Mitogenic augmentation of T cells from immunodepressed cancer patients by a murine interleukin-1 (IL-1).

An interleukin-1 (IL-1) lymphocyte-activating factor, with an approximate molecular weight of 13,000-16,000 was isolated from the culture supernatants of a murine macrophage-like cell line, P388D1. Contrary to the general belief that murine mediator is incapable of stimulating human lymphocyte mitogenic responses, leukoagglutinin (LA)-induced mitogenesis of peripheral blood lymphocyte (PBL) were significantly affected by murine IL-1. On one hand, when PBL were obtained from either normal healthy individuals or from cancer patients who still possessed normal levels of general immunocompetence, their mitogenic responses were not augmented any further by the murine mediator. Instead, slight but significant suppression were noted in most cases. On the other hand, the LA-induced responses of PBL from 5 immunodepressed cancer patients were markedly augmented by murine IL-1.

Adenocarcinoma↗
PubMed1984

Effects of three new folate antagonists on human breast adenocarcinoma cells in vitro and on immune responses in vivo.

The effects of three selected potential folate antagonists on 3H-leucine incorporation of eight established breast adenocarcinoma cell lines were investigated. The compounds studied were 5,8-dideazaisofolic acid, 5-methyl-5,8-dideazaisofolic acid, and 10-oxa-5,8-dideazafolic acid. All three anti-folates were inhibitory to most of the cells tested. 10-Oxa-5,8-dideazafolic acid was more effective in inhibiting the growth of these tumor cell lines. Both natural killer cell activity and phytohemagglutinin (PHA)-induced lymphocyte proliferation were decreased in hamsters injected with these compounds, with 5,8-dideazaisofolic acid being the most potent in this regard. The natural killer cell activity and lymphocyte proliferation returned to normal levels 12 days post-injection of these compounds. These studies suggest that 10-oxa-5,8-dideazafolic acid may be useful for the treatment of human breast tumors.

Adenocarcinoma↗
PubMed1984

Differentiation of prothymocytes induced by trypsin.

Treatment in vitro of nude mouse spleen prothymocytes with relatively low concentrations (1-50 micrograms/ml) of trypsin induce the Thy 1- to Thy 1+ conversion. The effect of trypsin was inhibited by prior heating or by addition of soybean trypsin inhibitor. The maximal effect achieved by trypsin treatment, approximately 25% conversion of spleen cells from layer B of an albumin gradient into theta-positive cells, was equivalent to that obtained with thymic hormone preparation (TP-1) at 10 ng/ml. Maximal conversion required 120 min incubation with TP-1 or trypsin. We conclude that both trypsin and TP-1 act by perturbation of a membrane receptor which can send a signal initiating the differentiation process.

Animals↗
PubMed1984

Specificity of antigen induced helper factor for antibody synthesis in vitro and its relation to lymphocytes interaction.

Human peripheral blood B-cells can be stimulated with PWM and antigen to produce specific antibody in vitro. This stimulation depends on the presence of T-cells and antigen. T cells, however, can be replaced by a soluble factor derived from a 48-hr culture of T-cells with either PWM and/or antigen. The helper factor, in the absence of antigen, acts as a polyclonal activator causing minimal proliferation of B-cells. When antigen is present, production of specific antibody is not dependent on the source of helper factor. Removal of monocytes abolished synthesis of both Ig and specific antibody although antigen and/or helper factor were present. While production of total IgG required autologous monocytes, the origin of the helper factor was not crucial. Production of specific antibody required that both monocytes and helper factor be derived from the same donor; therefore it seems that cooperation of B-, T-cells and monocytes for production of specific antibody is probably Ia restricted. In contrast, for production of polyclonal Ig (in the absence of antigen), cooperation of B-cells and monocytes with T-cells is not.

Antibody Formation↗
PubMed1984

Epidermodysplasia verruciformis: response to therapy with dialyzable leukocyte extract (transfer factor) derived from household contacts.

Dialyzable leukocyte extracts (DLE) have been used to treat a variety of antigen selective, and broad spectrum immunodeficiency diseases with sometimes encouraging results. We describe here the clinical and laboratory responses to DLE therapy of 2 patients with epidermodysplasia verruciformis (EV), a chronic cutaneous infection with a variety of human papilloma viruses. One patient with longstanding (30 yr) disease and no improvement to previous therapy showed gradual yet definite resolution of extensive verrucae planae, plaque, tinea-versicolor-like, and tumor lesions scattered over his entire integument. Cessation of DLE therapy for a short time resulted in recurrence of partially regressed lesions and also in the development of new tumors in this patient. The second patient, a grandson of the first patient, with minimal disease showed no progression of the disease during DLE prophylaxis. A third subject (brother of patient number 2) received no DLE and served as a control. All 3 subjects demonstrated severely depressed levels of suppressor T cells, a defect in cell-mediated immunity that has not been hitherto reported in patients with EV. Finally, evidence is presented for a possible X-linked recessive mode of inheritance for susceptibility to EV.

Adult↗
PubMed1984

Sigma receptors and autoimmune mechanisms in schizophrenia: preliminary findings and hypotheses.

Based on commonalities between peripheral blood "immunocytes" and central nervous system cells (both have receptors for endorphins, enkephalins, dopamine, acetylcholine, etc.) blocking of potassium ion channels in both brain cell synaptosome and suppressor T cells, and common sharing of antigenic determinants on one or another immunocyte and one or another CNS cells, we postulated that peripheral blood immunocytes can be used to study CNS mechanisms. In the present studies we used peripheral blood lymphocytes to study the effects of phencyclidine (PCP) on various receptors. This agent causes a permanent psychosis similar to chronic schizophrenia in a small percent of users. We observed similar effects in binding to sigma receptors, inhibition of binding and reversibility of binding in receptors of both human peripheral blood receptors and the mouse neuroblastoma, a hamster brain cell hybrid clone. The results are complete with the hypothesis that some cases of schizophrenia are immunologically mediated, perhaps due to antibodies to the sigma receptor. Alternatively, immunologic deficiency might hinder elimination of neurotropic viruses which in genetically predisposed individuals bind to and block the sigma receptor. Functional deficiency of the brain cell equivalent of lymphocyte suppressor T cells by one or another immunologic mechanisms or an excess of T helper cells might also cause schizophrenia by causing an excess of normal brain "B-cell equivalent cell" output response to sensory input.

Autoantibodies↗
PubMed1984

Guidelines for immunotherapy of antigen-specific defects with transfer factor.

Dialyzable leukocyte extracts (DLE) containing transfer factor (TF) with documented specificity for one or more microbial antigens have shown previously variable clinical effectiveness in treating many infectious diseases caused by viruses, fungi, protozoa and mycobacteria. The efficacy has sometimes been strong, and at other times dubious, in treating patients with inherited or presumably "acquired" immunodeficiency diseases refractory to standard therapy. The recent development of assays for screening leukocyte donors of DLE, for monitoring recipients, and especially for determining the potency of various DLE preparations containing antigen-specific TF and for predicting the clinical course of disease have, in our hands, greatly improved the likelihood of successful immunotherapy with TF. Two representative cases are reported, one involving a patient with an antigen selective defect to Candida, and another involving a patient with an antigen selective defect to Mycobacterium fortuitum. Both patients responded as judged by laboratory tests and clinical improvement when treated with certain DLE preparations but not with others. Finally, certain DLE preparations appeared to suppress cell-mediated immunity in vivo and this suppression could be predicted by in vitro tests. Based on these results, guidelines for optimal therapy with DLE are proffered .

Adult↗
PubMed1984

Antibodies to A19 and Bw35 complexes of human leukocyte antigens are present in infertile subjects with sperm antibodies.

Sera and secretions from 100 couples with unexplained infertility were tested for sperm antibodies by cytotoxicity and passive hemagglutination and also for antibodies to human leukocyte antigen (HLA) by cytotoxicity assays. Lymphocytes of the study subjects were typed for 61 HLA-A and B alleles. Thirteen of 30 (43%) men with sperm autoimmunity also had HLA antibodies in their serum and/or seminal plasma samples, in contrast to 2 of 35 (6%) nonautoimmune males (P = 0.0003). Twenty-five of 35 (71%) sperm antibody-positive infertile women had HLA antibodies in their sera and/or secretions, while only 7 of 31 (23%) women without sperm antibodies were positive (P = 0.00007). Antibodies to HLA-A19 (A26, A29, AW30, AW31, AW32, AW33, and AW34) and Bw35 (B5, B15, B17, and B18) complexes were present in 19 of 22 (86%) infertile men and 44 of 48 (92%) infertile women positive for HLA antibodies (P less than 0.01). The presence of antibodies to HLA-A19 and/or Bw35 in the infertile subjects did not correlate with the presence of HLA-A19 and/or Bw35 in the husbands. The presence of antibodies to HLA-A19 and/or Bw35 in the cervical mucus of the infertile women correlated with their presence in the seminal plasma of their husbands. It is suggested that antibodies to sperm antigens cross-reactive with HLA-A19 and/or Bw35 may be relevant to infertility.

Adult↗
PubMed1984

Immune diagnosis of a subset of Alzheimer's disease with preliminary implications for immunotherapy.

Based on remarkable similarities between the central nervous system and the immune system [e. g., both systems have memory cells, both appear to have identical receptors for dopamine, acetylcholine, enkephalins, endorphins, sharing of antigenic determinants on one or another CNS cell and one or another type of immunocyte cell, both systems communicate by soluble substances (e.g., neurotransmitters and lymphokines, respectively)], we have postulated that some forms of Alzheimer's disease are due not to CNS cell death but rather to excess suppression of the brain "B-cell equivalent". We found a pyrrolidone analog useful in stimulating lymphocyte B-cell mitogenesis and function in vitro; this agent subsequently proved dramatically effective in several patients with severe T cell dysfunction and severe recurrent viral infection due to excess T cell suppression. Its use (3-6 months) proved remarkedly effective in certain patients with Alzheimer's disease (frontal lobe cerebral atrophy on CAT scan, duration at least 2 years). A subset with certain immunological dysfunction responded dramatically both immunologically and clinically. In responders in in vitro studies, the defect was corrected in vitro in the presence of the pyrrolidone analog but not by various neuroleptics. Patients without the defect or with the defect but no in vitro correction by pyrrolidone analog agent did not respond clinically. A switch from pyrrolidone to placebo resulted in immunologic and clinical relapse in 2-4 months.

Adult↗
PubMed1984

Effect of polyvinyl pyrrolidone derivative compound on production of interleukin-1 by monocytes.

We studied the effect of 1-acetamide, 2-pyrrolidone (PVP-A), a B-cell mitogen derivative, on interleukin-1 (IL-1) production by peripheral blood monocytes. The compound was capable of inducing monocytes to produce IL-1 to an extent significantly lower than that induced by lipopolysaccharide (LPS). However, addition of PVP-A in conjunction with LPS resulted in IL-1 superinduction. Furthermore, PVP-A addition to monocytes of patients with Alzheimer's disease (AD) restored diminished IL-1 production by these cells to levels comparable with monocytes from age-matched healthy individuals. We also examined the effect of PVP-A on immunoglobulin (Ig) synthesis in vitro. PVP-A increased the production of both IgM and IgG by peripheral blood lymphocytes (PBL) in response to pokeweed mitogen (PWM). We conclude, since Ig synthesis of B-cells requires monocytes, that perhaps PVP-A activated monocytes can boost B-cells resulting in augmented Ig production.

Adult↗
PubMed1984

Isolation and characterization of an outer membrane protein of Salmonella paratyphi B: a mitogen and polyclonal activator of human B lymphocytes.

Salmonella paratyphi B (S. paratyphi B) has been previously characterized as a human T-independent polyclonal B cell activator. To define further the nature of the bacterial structure responsible for these properties, we studied the effects of autoclaving and enzyme treatment of S. paratyphi B on its stimulatory capacity. We found that both autoclaving and papain treatment decreased the ability of S. paratyphi B to induce B cell activation, while trypsin treatment did not affect this capacity. Neither type of treatment affected the binding of S. paratyphi B to lymphocytes, suggesting that binding and B cell stimulation are mediated by different structures. The observation that B cell stimulation was significantly reduced by papain treatment led us to attempt to purify membrane proteins so that we could investigate whether they shared the stimulating capacity of S. paratyphi B. A water-insoluble, 43-45,000 mol. wt. protein, rich in aspartic acid, glutamine, glycine, alanine and leucine, similar in mol. wt. and physicochemical chemical properties to the porins of other gram negative bacteria, was isolated and designated as outer membrane protein (OMP). This protein was equally efficient to S. paratyphi B in inducing T-independent B cell activation. By performing time-course studies of [3H]-thymidine incorporation we observed a burst of mitogenic activity after stimulation of PBL or purified B cells with both S. paratyphi B and OMP peaking at 48-96 hr of culture (compared to 96-120 hr for the PWM proliferation peak), and with a magnitude of roughly 10% of that observed after PWM stimulation. Given the fact that the proportion of B lymphocytes in PBL is 4-12%, it appears likely that the proliferation burst seen with S. paratyphi B and OMP corresponds to a mitogenic effect mainly restricted to the B cell population.

Amino Acids↗
PubMed1984

Sperm motility on postcoital testing correlates with male autoimmunity to sperm.

To assess whether or not immunologic factors in husbands, wives, or both, influence the motility of sperm in the female reproductive tract, hemagglutination and cytotoxicity sperm antibody (Ab) assays and postcoital tests (PCTs) were performed in 293 infertile couples. More couples without male autoimmunity to sperm (64% of 66; P less than 0.001) had greater than or equal to 10 motile sperm per high power field (adequate PCT), as compared with 26% of 122 couples with untreated male autoimmunity, 19% of 77 couples with corticosteroid-treated male autoimmunity without a pregnancy, and 36% of 28 couples with successfully treated male autoimmunity to sperm. Good correlation was obtained among pregnancy achievement, lack of sperm antibodies, and adequate sperm motility in the PCT (P less than 0.0001). Sperm motility in the PCT correlated positively with sperm motility in the semen and inversely with cytotoxic sperm Ab in the serum and seminal plasma of men and women and hemagglutinating sperm Ab in the cervical mucus samples. Sperm motility in the PCT has a predictive value of 72% for male autoimmunity and 57% for female isoimmunity to sperm in the presence of normal cervical mucus and in the absence of infections.

Adrenal Cortex Hormones↗
PubMed1983

T cell binding to B lymphoid cell lines in humans: a marker for T-B cell interaction?

Binding of human circulating T cells to established normal and malignant B cell lines results in rosette formation. The percentage of B cells, circulating T cells, and thymocytes able to bind to the B-LCL Raji were 0%, 59 +/- 4% and 61 +/- 6%, respectively. The percentage of rosettes formed between Raji cells and circulating mononuclear cells from 92 normal individuals was 27.8 +/- 5.3%, and remained stable over several months. This phenomenon seems to involve relatively mature B cells, and a T cell marker which appears early in T cell ontogeny. In the peripheral blood, most of the B-LCL binding T cells exhibit a 'helper-inducer' phenotype, as determined with the monoclonal antibodies Leu 3a and OKT4. However, a significant percentage of T cells with so-called 'cytotoxic-suppressor' markers (Leu 2a and OKT8) also bind to B-LCL. The T cells involved in this morphological interactive reaction with B cells might conceivably be specifically involved in regulating B cell functions. Enumeration of this particular subset may be useful in conditions where abnormal T-B cell interactions are suspected.

Antibodies, Monoclonal↗