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Biomedical subjects

H H Fudenberg

Publications and source records attributed to H H Fudenberg.

At least 199 records · Page 11Linked to original sources
PubMed1979

Effects of dialyzable leukocyte extracts (DLEs) with transfer factor activity on leukocyte migration in vitro. III. Characterization of the antigen-independent migration inhibition factor in DLEs as a neutrophil immobilizing factor.

In earlier evaluations of the agarose LMI assay as an in vitro test for studying the nature and mechanism of action of TF, we reported the existence of a component in human DLEs which caused noncytotoxic inhibition of the random migration of human PMNs. The LMI was not dependent on the stimulation of viable mononuclear leukocytes by antigen or mitogen to effect the release of mediators of cellular immunity such as LIF; rather, the LMI was promoted by the direct action of a preexisting component in DLEs on PMNs. We now present evidence that this "antigen-independent" LMI activity in DLE'S is similar to a NIF shown previously by Goetzl and co-workers to be present in acid extracts of leukocytes and to be released by phagocytosing PMNs. The comparison is drawn from several parameters: (1) cellular origin, (2) molecular weight, (3) target cell, (4) susceptibility to inactivation by heating or by incubation with pronase, trypsin, or chymotrypsin, and (5) ability to cause noncytotoxic inhibition of random migration or chemotaxis of PMNs.

Animals↗
PubMed1979

Immunoglobulin allotypes and response to tetanus toxoid in Papua, New Guinea.

The data indicates that Papuans with the Austronesian haplotype Gmf,a;b produce significantly higher levels of tetanus specific antibody, than Papuans without this haplotype, suggesting that response to tetanus toxoid in man is associated with the Gm phenotype of the individual. Km (1) status was not related to response.

Antibodies, Bacterial↗
PubMed1979

Active and suppressor T cells: diminution in a patient with dyskeratosis congenita and in first-degree relatives.

Active, total and nonspecific suppressor T cells were studied in a 15-year-old black male with dyskeratosis congenita syndrome, a precancerous mucosal disease, and in 7 siblings and several other relatives in three generations. The propositus and 1 elder sister, products of a second-cousin marriage, died with dyskeratosis congenita. The mother had dermatomyositis, and the maternal grandmother and her sister reportedly had rheumatoid arthritis. Studies of available siblings, father, and grandparents revealed a high incidence of deficiency in number of active and/or suppressor T cells, sometimes severe enough to result in a decrease in total T cells. The patient had many stigmata of precocious aging, as did the sibling who died with the same syndrome. The laboratory data suggest that a defect in cell-mediated immunity, involving mainly or exclusively suppressor T cells, is associated with, and is presumably the cause of, precocious aging; perhaps an abiotrophy in this cell subpopulation results in physiologic aging.

Adolescent↗
PubMed1979

Nephelometric detection of soluble immune complexes: methodology and clinical applications.

We have developed a method for the detection of immune complexes by laser nephelometry which is simple, reproducible, suitable for automation, and generally adaptable for diagnostic testing. Light dispersion by antigen-antibody complexes in the test samples is measured after addition of polymeric buffer, which enhances the aggregation of complexes but does not significantly affect unbound immunoglobulins. The method was used to measure immune complexes formed in vitro by incubation of tetanus toxoid with serum from a rabbit previously hyperimmunized with the same antigen, and to compare the levels of immune complexes in human sera obtained from normal adults and from 37 patients with collagen vascular diseases or endocarditis. When precautions were taken to avoid interference produced by the presence of lipoproteins or by freezing of the samples, the results obtained with human sera were consistent with those expected for normal controls and for patients with conditions thought to be associated with the presence of soluble immune complexes.

Animals↗
PubMed1979

Evidence for the synthesis and release of strongly immunosuppressive, noncytotoxic substances by Streptococcus intermedius.

Products secreted by Streptococcus intermedius were studied for their effects on the immune response. Three different preparations of crude extracellular products from S. intermedius (CEP-Si) were found to have powerful suppressor activity in vitro as shown by inhibition of human lymphocyte proliferation (uptake of [3H]thymidine) and protein synthesis in response to a wide variety of stimulants, including mitogens and antigens, and suppression of plaque formation by human cells in response to sheep erythrocytes. CEP-Si was noncytotoxic, because cells incubated with high concentrations of CEP-Si and subsequently washed were viable and recovered their ability to respond to mitogens, and because leukocyte migration was not inhibited by CEP-Si, nor was the release of leukocyte migration inhibitory factor from sensitized lymphocytes. The possibility of antigen or mitogen competition was excluded. The effects of CEP-Si in vitro were time dependent and did not require the presence of monocytes. Cells pretreated with CEP-Si and then washed suppressed plaque formation by fresh autologous cells in highly stimulated cultures. CEP-Si injected into C57BL/6 mice also strongly suppressed their immune response to sheep erythrocytes, and the in vivo suppression was correlated with the effects of CEP-Si in vitro.

Animals↗
PubMed1979

Activation of human lymphocytes by supernatants from human thymic epithelium.

Supernatants from human thymic epithelial cells (TS) were found to have a mitogenic effect on cultured human peripheral blood mononuclear cells and to potentiate their responses to lectins. This was not observed with culture supernatants from the human cell lines AV-3 and HeLa or from the murine cell line L-929. The maximum potentiating effects were observed with pokeweed mitogen (PWM) and phytohaemagglutinin (PHA), whereas the response to concanavalin A (Con A) was only slightly enhanced. TS also potentiated the mixed lymphocyte culture (MLC) response of normal T cells and thymocytes cultured with mitomycin C-treated B lymphoid cell lines. The mitogenic effect of TS was time-dependent and paralleled the appearance of lymphoid colonies in semi-solid agar. Chromatographical separation of concentrated serum-free TS on Sephadex G-100 yielded an active fraction of molecular weight 15,000--25,000 which had all the activities of unseparated TS.

Cells, Cultured↗
PubMed1979

Cell-mediated immunity in vitro in atopic dermatitis.

The function of T cells in atopic dermatitis was studied by leukocyte migration agarose and lymphocyte transformation tests. We found that phytohemagglutinin (PHA)- and PPD-induced release of leukocyte migration inhibition factor (LIF) from lymphocytes is significantly decreased (P less than .001) in patients with atopic dermatitis as compared with healthy controls. Blastogenic response of lymphocytes induced by PPD was also decreased in atopic patients as compared with controls (P less than .01). No differences were found in spontaneous blastogenesis or in blastogenic response of lymphocytes in vitro to PHA, concanavalin A (ConA), or streptokinase-streptodornase (SK-SD) between patients with atopic dermatitis and controls.

Adolescent↗
PubMed1979

Stimulators and inhibitors of lymphocyte DNA synthesis in supernatants from human lymphoid cell lines.

Some T and B lymphoid cell lines (LCL) were found to secrete into their supernatants a substance able to stimulate lymphocyte proliferation. This substance produced an increase in [3H]thymidine uptake by mononuclear cells when added to unstimulated cultures (mitogenic effect) or when added to cultures stimulated with phytohemagglutinin (PHA) or pokeweed mitogen (PWM) (potentiating effect). When complete supernatants were used, the potentiating effect was sometimes masked by an inhibitor of DNA synthesis. Fractionation on Sephadex G-100 separated these two activities. The stimulatory substance eluted at a m.w. range of 15,000 to 30,000, and the inhibitor eluted with the albumin peak. B cells with or without monocytes were the most sensitive to the mitogenic effect, whereas T cells were unaffected. Responses to PHA and PWM were potentiated when T cells were present, but the maximum effect was observed when the proportion of T cells was less than 50%. The stimulatory material may be similar to lymphocyte mitogenic factor and may function as a T cell-replacing factor in B cell stimulation.

Cell Line↗
PubMed1979

Induction of extraglomerular renal damage in experimental chronic serum sickness. I. Histologic and immunofluorescence findings.

Histologic and immunofluorescence studies were performed in nine rabbits after daily administration of human serum albumin at a fixed dosage for periods up to 26 weeks. All but one of the rabbits studied by immunofluorescence showed IgG, C3, and fibrinogen deposits in the renal glomeruli and in the tubules or peritubular tissues. In most cases, human serum albumin could also be identified in the deposits. In two rabbits killed at week 10, kidney pathology was minimal; in one of the rabbits killed in the early phases of the disease and in all rabbits killed after week 20, there were obvious pathologic changes affecting glomeruli, tubules, and/or interstitium. Tubulointerstitial changes were absent in only one of the rabbits killed at late stages of human serum albumin administration, in spite of evidence of tubular deposition of immune complexes. These observations suggest that tubulointerstitial damage is at least as frequent as glomerular damage during the induction of chronic serum sickness.

Animals↗
PubMed1979

Effects of dialyzable leukocyte extracts with transfer factor activity on leukocyte migration in vitro. 1. Antigen-dependent inhibition and antigen-independent inhibition and enhancement of migration.

The effects of DLE containing TFd activity from immune human donors on PBL, obtained from individuals nonresponsive to either PPD or Cocci antigen, were evaluated in vitro by the agarose LMl technique. Several different preparations of DLE were employed to evaluate the specificity and reproducibility of the effects: (1) from donors skin test positive to PPD but negative to Cocci, (2) from donors skin test negative to PPD but positive to Cocci, (3) from donors skin test positive to both antigens, and (4) from donors skin test negative to both antigens. With PBL from other human donors used as target cells in the direct agarose LMi technique, three types of effects were demonstrated for all preparations of DLE: (1) antigen-dependent specific LMl, (2) antigen-independent or nonspecific LMl, and (3) antigen-independent enhancement of migration. The demonstration of each activity was found to depend on the concentration of DLE used and the time allowed for migration. In experiments employing purified PMN and MNL as target cells and a two-step indirect LMl assay, it was shown that the antigen-independent effects resulted from the direct of components in DLE on PMN. The antigen-independent inhibition was shown not to result from toxic effects of DLE. It was produced by DLE but not by dialyzable liver or skin extracts when tested using an amount equivalent to DLE as judged by the absorbance at 260 and 280 nm. The antigen-dependent LMl was found to require secretion of a soluble mediator of molecular weight near 69,000, believed to be LMl. Our results indicate that the agarose LMl technique is a useful in vitro assay for studies of the mechanism of action of components in DLE which can specifically convert nonimmune lymphocytes to a measurable antigen-sensitive state (i.e., transfer factor). The antigen-independent effects of DLE may be responsible in part for previously reported nonspecific beneficial effects of DLE when used in immunotherapy.

Antigens↗
PubMed1979

Effects of dialyzable leukocyte extracts with transfer factor activity on leukocyte migration in vitro. II. Separation and partial characterization of the components in DLE producing antigen-dependent and antigen-independent effects.

Previous studies have shown that DLEs with TFd activity produce both Ag-dependent specific effects (mediated by TFd) and Ag-independent effects on CMl as demonstrated in vitro by agarose LMl. In the present study, Sephadex G-25 gel filtration provided a simple method for separating the DLE components responsible for each effect into distinct fractions. Ag-independent LMl was produced predominantly by Sephadex fraction l, of MW greater than 5000. The active components, further purified on Bio-Gel P-10, were shown to be of MW 14,000 to 17,000 and to contain both polypeptide and ribonucliotide material. The Ag-independent LMl activity was stable to heating at 56 degrees C for 30 min but was partially destroyed at 80 degrees C for 30 min, and the responsible components were shown to act on PMN directly. Ag-independent ELM was produced exclusively by material in Sephadex G-25 fraction V and also acted directly on PMN, whereas the Ag-dependent specific LMl activity was found predominantly in fraction lVb and to a lesser extent in fraction V and could not be detected in a direct assay using only PMN. In addition, a new activity, designated "Ag-dependent ELM activity," which caused increased migration in the presence of Ag, was found in Sephadex fraction lVa. This latter activity might mask the Ag-dependent LMl activity in fraciton lVb. Bio-Gel P-2 chromatography separated the components producing Ag-dependent and Ag-independent effects in fraction V into two separate subfractions (Va and Vb) of MW 1100 to 2000 and less than 900. The activity in fraction lVb eluted at a position identical to that of the components in fraction Va on Bio-Gel P-2. Fractions Va and Vb contained both polypeptide and ribonucleotide material. The Ag-dependent specific LMl or TFd activity was found to be partially inactivated at 56 degrees C and completely destroyed at 80 degrees C. The components responsible for this TFd activity were further purified by HPLC on ODS resin. The TFd activity was mediated by components with retention times much greater than that of adenosine 3'-monophosphate. The active fraction was composed of both polypeptide and ribonucleotide material but did not contain deoxyribonucleotides.

Antigens↗
PubMed1978

Monoclonal IgM cryoglobulinemia associated with gamma-3 heavy chain disease: immunochemical and biochemical studies.

A patient (Mia) with a monoclonal IgM(kappa) cryoglobulin (cryo IgM) developed additional heavy chain disease proteins of the gamma3 subclass 8 years later. Biochemical studies of the cryo IgM indicated that the heavy chain was VHI, but the NH2-terminal amino acid sequence of the light chain did not permit a definite assignment of its Vkappa subgroup. Two major fragments of the gamma3 chain were distinguishable by electrophoresis in sodium dodecyl sulfate polyacrylamide gel. The smaller component (designated Mia F) had a molecular weight of approximately 30 000 and the larger component (designated Mia S) 35 000. Both fragments had G3m(21) and G3m(27) allotypic determinants. These data and the NH2-terminal amino acid sequence of the gamma chain fragments suggested that Mia S consists of the major part of the gamma3 hinge region plus the CH2 and CH3 domains of the gamma3 chain, whereas Mia F may be derived from the former as a result of postsynthetic cleavage. The partial amino acid sequence of the Mia S fragment is homologous to the hinge region amino acid sequence of human gamma3 chains reported in the literature, with only one amino acid difference out of the 11 residues compared. This difference may represent an allotypic difference within the gamma3 subclass. Alternatively, the production of Mia S may have resulted from the accidental derepression of a "silent" constant region gene not expressed in normal individuals.

Amino Acid Sequence↗