Gamma heavy chain disease protein CHA: immunological and structural studies.
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Amino Acid Sequence↗
Biomedical subjects
H H Fudenberg
Publications and source records attributed to H H Fudenberg.
Resynthesis of trypsinized sheep red blood cell receptors on human lymphocytes: comparison of the effects of immunopotentiators of biological and synthetic origin in vitro.
Five immunostimulants--thymosin, dialyzable leukocyte extracts containing transfer factor (DLE), isoprinosine, BM 12 531 (azimexon), and levamisole--were compared separately and in various combinations for their ability to increase the binding of sheep erythrocytes by trypsinized human peripheral blood lymphocytes in vitro. Levamisole produced the greatest enhancement when used alone, DLE produced a smaller increase, and isoprinosine, thymosin, and BM 12 531 were less effective. When combining two of these agents, the greatest increase was seen when one of the components was thymosin and the other either DLE, isoprinosine, or BM 12 531. These results indicate possible synergistic mechanisms and the possible advantage of combined therapeutic use of selected combinations of immunostimulants. In the majority of the combinations, however, inhibition rather than stimulation of rosette formation was observed.
Adjuvants, Immunologic↗
Isoprinosine as an immunopotentiator in an animal model of human osteosarcoma.
The effects of isoprinosine (ISO) on the immune responses (Con A-induced lymphocyte proliferation, monocyte chemotactic responsiveness, and "natural killer" cytotoxicity) of normal hamsters and hamsters with human osteosarcoma (OS) were investigated. Human osteosarcoma was induced in newborn inbred hamsters (LHX/SsLAK) after induction of tolerance in utero. In vitro, ISO increased Con A-induced proliferation of peripheral blood lymphocytes (PBL) from normal hamsters by 23.4-48.9% and from OS-bearing hamsters by 58.1-107.4% over controls (Con A alone). When ISO was administered in vivo by intraperitoneal injection. Con A-induced proliferation of PBL from both normal and OS-bearing recipients in vitro was increased by 50-55% at 1, 3 and 5 days after injection. The chemotactic responsiveness of monocytes from OS-bearing hamsters was also significantly increased (59.1-97.4%) at 1, 3 and 5 days after injection of ISO. Natural killer cytotoxicity was augmented at 1, 3 and 5 days after injection of ISO by 31.7-83.6% in normal hamsters and 54.6-184% in OS-bearing hamsters. These results indicate that ISO can produce a generalized enhancement of immune function in hamsters with OS.
Adjuvants, Immunologic↗
HLA antigens and immunoglobulin allotypes in patients with malignant melanoma.
HLA antigens and Gm, A2m, and Km allotypes were examined in Caucasian patients with malignant melanoma. No significant associations were found for any of the HLA antigens tested. Significant association was found with Gm(2), and the relative risk for individuals with this marker was calculated at 1.9. The data indicate that Caucasians positive for Gm(2) are almost twice as likely to develop malignant melanoma as those without this marker.
HLA Antigens↗
Cross-reactivity of sperm and T lymphocyte antigens.
Evidence is presented for cross-reactivity between antigens on human sperm and T lymphocytes. In 25 infertile couples in which both the males and females had significant antisperm immunity, antibody (Ab) titers to thymocytes (mean +/- S.E.M. 159 +/- 4 and 72 +/- 14, respectively, in males and females), T cell lines CCRF-CEM (69 +/- 5 and 48 +/- 8) and HSB-2 (56 +/- 15) and 41 +/- 8), suppressor-enriched (TG) cells (26 +/- 6 and 66 +/- 28) and helper-enriched (TG-) cells (26 +/- 4 and 46 +/- 14) were significantly elevated, as compared with Ab titers in 45 normal males and 45 normal females without antisperm immunity. Antibody titers to adult B cells, B cell line RAJI, and granulocytes were similar in the two groups. Antisperm Ab titers in sera, sperm extracts, and seminal plasma of the infertile subjects were significantly reduced after absorption with sperm, thymocytes, or T cell line CCRF-CEM but not with the B cell line RAJI. Antithymocyte Ab titers in the sera were significantly reduced (p less than 0.001) after absorption with thymocytes, CCRF-CEM, or sperm, but not RAJI. Lymphocytes from the infertile patients, when stimulated with pokeweed mitogen in vitro, produced antisperm and anti-T-lymphocyte antibodies at significantly higher titers than normal controls.
Antibodies↗
Pi-Gm linkage: evidence for linkage in males but not in females and for an effect of the S allele of the Pi system.
Linkage between the Pi (alpha 1-antitrypsin) and Gm (immunoglobulin heavy chain) loci was studied in thirty-four families including forty-one informative parents and 142 children. In females, the results did not provide evidence for linkage (posterior probability of non-linkage 0.98). In contrast, in males, there was strong evidence for linkage (peak lod 3.9 at theta = 0.18, posterior probability of linkage 0.98). The two populations appeared to be significantly different (0.001 less than P less than 0.01) with respect to the heterogeneity criterion of Morton. In addition, the effect of the possession of the S allele (associated with significantly decreased serum alpha 1-antitrypsin levels) was studied in fifteen informative parents and fifty-three children of the same group. No evidence for or against linkage was found in females, but in males close linkage between Pi S and Gm was demonstrated (peak lod 7.7 at theta = 0.05, posterior probability of linkage 0.9999). These data indicate significant linkage between Pi and Gm in males but not females and close linkage between the Pi S and Gm markers in males.
Alleles↗
Immunoglobulin G heavy chain (Gm) allotypes in multiple sclerosis.
Serum samples from 70 Caucasian patients with multiple sclerosis were typed for nine Gm markers. Significant association was found with the Gm 1,17;21 phenotype, and the relative risk for individuals with this phenotype was calculated at 3.6. The data indicate that Caucasians positive for Gm 1,17;21 are almost four times more likely to develop multiple sclerosis than those without this phenotype.
Hemagglutination Tests↗
Cystic fibrosis ciliary dyskinesia substances and pulmonary disease. Effects of ciliary dyskinesia substances on neutrophil movement in vitro.
Cultured mononuclear cells (MNC) from individuals homozygous or heterozygous for the defective gene causing the inherited disease cystic fibrosis (CF) synthesize three unusual "mediators" termed ciliary dyskinesia substances (CDS), which markedly affect tracheal mucociliary systems in vitro. MNC cultures from normal healthy controls do not accumulate any CDS, whereas MNC cultures from non-CF patients controls with pulmonary disease synthesized at least one CDS. The possible involvement of the CDS in pulmonary disease is being investigated. In this study, we sought to determine whether the CDS could be chemoattractants for polymorphonuclear neutrophils (PMN), since they have characteristics in common with known chemoattractants generated by alveolar macrophages. Our analyses of crude MNC culture supernates indicated that cultures from both CF genotypes accumulate significantly higher levels of PMN chemoattractants than do analogous cultures from normal healthy controls. CF homozygote MNC also generated more activity than MNC from patient controls with chronic pulmonary disease. Fractionation of MNC culture supernates by gel permeation chromatography and characterization of active fractions demonstrated six distinct PMN chemoattractants in cultures from CF genotypes; five were also present in patient control and four in normal healthy control cultures. The excessive chemoattractant activity in MNC cultures from CF genotypes and patient controls was due to several different substances produced by monocytes: (a) two components of 1,000-3,500 mol wt. (b) two fragments of C5, and (c) a fragment of C3. One C5 fragment had ciliary dyskinesia activity, the other did not. The C3 fragment chemoattractant also had ciliary dyskinesia activity and was not found in MNC cultures from patient controls. A third CDS, Which is CF-specific (5,000 mol wt), was neither chemotactic not chemokinetic and did not inhibit random PMN migration; however, fractions containing this CF-specific CDS completely inhibited PMN chemotaxis in response to three different chemoattractants. We conclude that all of the CDS can potentially play a role in the pathophysiology of lung disease, as judged by their effects on PMN movement in vitro.
Biological Assay↗
Fractionation and characterization of the immunosuppressive substance in crude extracellular products released by Streptococcus intermedius.
The noncytotoxic immunosuppressive substance detected in crude extracellular products of Streptococcus intermedius (CEP-SI) was fractionated by two steps of preparative isoelectric focusing in sucrose gradients using ampholytes of pH range from 3.5 to 6 and 4 to 5, respectively. The in vitro and in vivo suppressor effects of the most highly purified fraction of CEP-Si, designated fraction 3' (F3'EP-Si), corresponded well with those of the original CEP-Si. F3'EP-Si was sensitive to the effects of alpha, gamma, and delta chymotrypsin, trypsin, and heating. It contained approximately 1% of the total amount of protein found in the original CEP-Si, corresponding to a single band on analytical isoelectric focusing, stainable by Coomassie Blue and of isoelectric point of 4.25. The absorption spectrum of F3'EP-Si had a maximum at 260 nm but its biological activity was resistant to deoxyribonuclease and ribonuclease A and it did not contain material stainable by methylene blue. It was also resistant to neuraminidase and did not contain material stainable by periodic acid schiff. We conclude that the substance responsible for the suppressor activity of CEP-Si is a protein of molecular weight approximately 90,000, which adheres to Sephadex of cellulose acetate and forms complexes with other, nonactive constituents of CEP-Si.
Antigens↗
Immunoglobulin allotypes and immune response to meningococcal group B polysaccharide.
Serum samples were collected from 120 healthy adult volunteers (105 Caucasians and 15 Negros) before and after immunization with meningococcal polysaccharide (MPS) group B vaccine. Antibodies to MPS group B were measured and sera were typed for several Gm and Km(1) allotypes. A significant association was found between the Km(1) allotype and immune response to MPS group B in Caucasians.
Adolescent↗
Differences in mitogenic responses of murine T cells to two distinct phytohemagglutinin (PHA) subcomponents.
Two distinct mitogenic subcomponents of phytohemagglutinin (PHA)--leucoagglutinin (LA) and "purified" PHA--apparently stimulated different subpopulations of murine T cells. In the DBA/2J strain, the mitogenic responses of splenic lymphocytes to LA reached maximal levels after 24 to 36 hr exposure and almost completely disappeared by 48 hr, whereas maximal responses to PHA were maintained after 48 hr incubation. The levels of LA-responding T cells were highest in DBA/2J spleens at 5 weeks of age but markedly declined by 9 weeks of age, whereas thymic levels of LA-responding T cells reached a maximum at 9 weeks of age and remained maximal past 15 weeks of age. PHA-responding cells, in contrast, reached maximal levels in both the spleen and thymus of DBA/2J mice at 9 weeks of age. In C57BL/6J mice, splenic and thymic lymphocytes responded similarly to both components, except that the response of splenic lymphocytes to PHA reached a maximum after shorter incubation time and declined sooner than their response to LA. The mitogenic responses of C57BL/6J thymocytes to both components were already at their peak by 5 weeks of age and almost totally disappeared by 9 weeks, whereas the responses of splenic lymphocytes were maximal at 9-15 weeks of age. The responses of DBA/2J splenocytes to LA was significantly augmented by PHA, but LA markedly suppressed the proliferative responses to PHA.
Aging↗
Effects of dialyzable leukocyte extracts with transfer factor activity on leukocyte migration in vitro. V. Antigen-specific lymphocyte responsiveness can be initiated by two structurally distinct polyribonucleopeptides.
Human transfer factors (TF) active in specifically inducing responsiveness in human thymus-derived (T) lymphocytes previously nonresponsive to purified protein derivative from Myobacterium tuberculosis (PPD) or to Coccidioides immites (Cocci) in vitro were isolated from the dialyzable portion of extracts of immune leukocytes (DLE). Each TF segregated into two active fractions after high-pressure reverse-phase liquid chromatography (HPLC), suggesting the presence of two TF components in DLE for each antigen specificity. Determination of the structures of both TF components specific for PPD was accomplished by evaluating their activity after incubation with various endonucleases, exonucleases, phosphatases, peptidases and a protease. The results indicated that both PPD-specific TF components are oligoribonucleopeptides but that they are structurally distinct. Simplest-case molecular models were constructed on the basis of the data obtained.
Cell Extracts↗
Isolation and characterization of an age-related antigen present on senescent human red blood cells.
Autologous membrane-bound IgG was isolated from a subpopulation of human red blood cells (RBC) with specific density greater than 1.110, by affinity chromatography of purified RBC membrane glycoprotein preparations using immobilized wheat germ agglutinin and immobilized anti-human immunoglobulin (Ig) as immunoabsorbents. The Ig-containing population thus obtained, when further separated by chromatography on Sephadex G-200 in the presence of chaotropic agents, yielded four peaks (Ia, Ib, II, and III). Double immunodiffusion revealed the presence of Ig in the first three peaks (IgM in peak Ia, IgA in Ib, and IgG in II) but not in peak III. Peak III was precipitated by the Ig-containing peaks (Ia, Ib, and II) in immunodiffusion assays, suggesting that the antigenic membrane determinants responsible for the binding of autologous Ig to senescent human RBC were contained in this peak (III). Peaks Ia, Ib and II precipitate purified asialoglycophorin; peak III was reactive with purified autoantibodies directed against asialoglycophorin. These results suggest that an age-related antigenic determinant(s) present on senescent human RBC is exposed by desialylation of the major sialoglycoprotein component of the RBC membrane.
Adult↗
Osteosarcoma patients: isolation of serum antibodies by affinity chromatography.
Antibodies specific for membrane-associated antigens of human osteosarcoma cells were isolated from sera of 12 patients with osteosarcoma (OS). Affinity columns were prepared by coupling purified membrane antigens from cultured human OS cell lines (TE-85 or LM) to CBrN-activated Sepharose 4B. The antigens were prepared by discontinuous sucrose gradient ultracentrifugation, papain digestion, and DEAE column chromatography. Diluted serum was passed over the affinity columns, and the adsorbed proteins were eluted with 2.5 M MgCl2 (pH 6.5). Immunodiffusion, indirect immunofluorescence, and complement fixation were used to assay antibody activity in the eluate. Specific anti-OS activity was found in the immunoglobulin (Ig) fraction isolated from the sera of the 12 OS patients, as confirmed by blocking experiments. No anti-OS antibody activity was found in sera from healthy individuals or patients with breast carcinoma, clear cell liposarcoma, or leukemia in this study. The anti-OS activity of the isolated Ig from OS patients was abolished after absorption with cultured human OS cells from lines LM, TE-85, or G292 but not after absorption with cells from lines WI-38 (embryonic lung), TE-32 (rhabdomyosarcoma), CAMA-1 or SW527 (breast carcinoma), or M-14 (melanoma). Absorption with rabbit antihuman IgG but not with rabbit antihuman IgM immunobeads completely eliminated the antibody activity.
Antibodies, Neoplasm↗
Evidence for the presence of a low molecular-weight activator of suppressor monocytes (LASM) in dialysates of T lymphocytes.
Lysates of peripheral blood T lymphocytes from healthy individuals were found to contain a low molecular-weight peptide that inhibited phytohaemagglutinin-induced DNA synthesis in vitro by autologous or allogeneic peripheral blood mononuclear cells. The peptide was dialysable, partially heat stable, resistant to trypsin, RNase, and DNase but not to pronase, and was not part of the membrane receptor involved in rosette formation by T lymphocytes with sheep erythrocytes. It was found to act through monocytes, inducing the synthesis of second mediator responsible for the inhibition of lymphocyte DNA synthesis. This inducer of inhibition, designated as "low molecular-weight activator of suppressor monocytes' (LASM), may have a role in the depression of cellular immune response seen in various pathological conditions involving the destruction of T lymphocytes.
Adult↗
"Discoid" lupus erythematosus: dramatic clinical and immunological response to dialyzable leukocyte extract (transfer factor).
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Adult↗
Clinical significance of sperm antibodies in infertility.
Sperm antibody (AB) titers, determined by passive hemagglutination and cytotoxicity assays, were found to be elevated in 62 males and 46 females of 103 couples with primary infertility; 15 males and 12 females of 25 couples with secondary infertility; 10 males and 8 females of 18 couples with histories of repeated abortion; 21 males and 17 females of 25 couples in which the husband had a history of prostatitis; and 29 males and 17 females of 38 couples in which the husband had oligospermia. Of the couples in which one or both partners had elevated sperm AB titers, only 4 achieved pregnancy: 3 from the group with secondary infertility, all of which ended in spontaneous abortions, and 1 in which the husband was oligospermic. This suggests an etiologic role of sperm immunity in infertility. Immunosuppressive treatment of autoimmune males with prednisone (15 mg/day for 3 weeks to 6 months) resulted in significant decreases in AB titers. Pregnancies were achieved by 9 of 25 couples after treatment (36%). The observed increase in pregnancy rate in the prednisone-treated versus untreated groups of couples with elevated sperm AB titers was significant (P less than 0.02).
Abortion, Habitual↗