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Biomedical subjects

R A Good

Publications and source records attributed to R A Good.

At least 199 records · Page 11Linked to original sources
PubMed1991

Transplantation of wheat germ agglutinin-positive hematopoietic cells to prevent or induce systemic autoimmune disease.

Hematopoietic stem cell defects are thought to be involved in the etiopathogenesis of systemic autoimmune disease. Positively selected, stem cell-enriched populations of wheat germ agglutinin-positive (WGA+) low-density bone marrow and fetal liver cells from normal and autoimmune-prone mice were used to determine whether reciprocal transplantation of stem cells between normal and autoimmune-prone mice inhibits or causes development of autoimmune disease. NZB recipients of DBA/2 stem cell populations analyzed greater than 100 days after bone marrow or fetal liver cell transplantation showed decreased levels of anti-DNA antibodies and decreased glomerular lesions when compared with nontreated NZB mice or NZB recipients of NZB stem cell preparations. Female DBA/2 recipients of WGA+ NZB bone marrow cell or fetal liver cell transplants exhibited elevated serum autoantibody levels and developed glomerular lesions characteristic of NZB mice when analyzed greater than 100 days after transplantation. These pathological disturbances were not observed in DBA/2 recipients of DBA/2 stem cell preparations. The data indicate that WGA+ stem cells from autoimmune-prone NZB mice contain the genetic defects responsible for the development of systemic autoimmune disease.

Animals↗
PubMed1991

NZB serum factor (NZB-SF): B precursor cell maturation factor identified in murine lupus. I. Identification of 60-kDa glycoprotein as the major component from both spleen cell supernatant and serum.

NZB serum factor (NZB-SF), initially identified in sera of very young NZB mice, can enhance maturation and proliferation of sIg- pre-B cells in marrow. In the present study, spleen cell supernatant from young NZB mice was used as a source of NZB-SF. NZB mice were treated with Corynebacterium parvum 2 weeks prior to sacrifice, and harvested spleen cells obtained at sacrifice were cultured for 24 hr in serum-free medium. One liter of spleen cell supernatant prepared in this way contained NZB-SF-like activity equivalent to that present in 10 ml of serum collected from young NZB mice. NZB-SF was purified on an affinity chromatographic column conjugated with mouse IgG1 monoclonal antibody (mAb) against NZB-SF. The purified NZB-SF had pI 7.8 and showed one major band of 60 kDa and a faintly stained 35-kDa band upon SDS-PAGE under nonreducing conditions. The 60-kDa NZB-SF extracted from the gel slice was also more potent in dot blot ELISA (greater than 100 times) than the 35 kDa NZB-SF and was biologically active. After endoglycosidase F treatment, but not after treatment with a reducing agent (2-ME), the two bands merged into a single band at the 15-kDa position. Amino acid sequence analysis of endo-F treated NZB-SF indicated that the N-terminus of this protein is blocked. Serological and functional studies of affinity-purified NZB-SF have revealed that NZB-SF is distinguishable from IL-1 alpha, IL-2, IL-3, IL-4, IL-5, IL-6, CSF-GM, IFN-gamma, and TNF alpha. Therefore, a major component of NZB-SF(s) in the spleen cell supernatant may be an apparently novel 60-kDa glycoprotein with a single amino acid backbone. Sera and spleen cell supernatants from normal strains of mice (DBA/2, B6, or BALB/c) were also applied to the immuno-affinity column used to purify NZB-SF. It was found that trace amounts of NZB-SF are present also in serum of normal strains of mice and that spleen cells of these mice can also produce NZB-SF in vitro following stimulation with C. parvum. In SDS-PAGE, the 60-kDa NZB-SF is also the major component of NZB-SF in normal strains of mice. These results suggest that the 60-kDa NZB-SF may be of physiological importance in B cell differentiation and that this physiological factor is autoimmune-prone NZB mice.

Animals↗
PubMed1991

Two populations of guinea pig erythrocyte-rosetting cells in the cat: evidence for their T-helper function in mitogen-induced synthesis of Ig and interleukin-2.

Studies in our laboratory have shown that T-helper (T-H) and T-suppressor (T-S) cells in cat peripheral blood leukocytes (PBL) rosette with guinea pig (GP) and gerbil (G) erythrocytes (E), respectively. Removal of GE-rosetting cells leads to an enhanced (two- to threefold) synthesis of Ig in a pokeweed mitogen (PWM)-driven system as measured by plaque-forming cells (PFC) to protein A-coated sheep RBC, while depletion of GPE-rosetting cells yields a PFC response only 10-15% of the control. Surprisingly, removal of both GE- and GPE-rosetting cells gave a response equivalent to 40-100% of the control PBL. Analysis of the mixed GE/GPE rosette depleted cultures revealed the reappearance of GPE- but not GE-rosetting cells, reaching maximum values within 12-18 hr after in vitro culture. Cultures of control PBL and those following the mixed rosette depletion showed two populations of GPE-rosetting cells; the GPE-1 cells, present on Day 0 before culture, and the GPE-2 cells, those appearing on Day 1. Addition of cycloheximide prevented development of the GPE receptor while colchicine and mitomycin C were without effect. The development of PFC after the mixed GE/GPE rosette depletion was interpreted as being due to the GPE-2 cells functioning as T-H cells in the absence of any T-S (GE-rosetting) cells. This thesis was supported by showing a marked decrease in the PWM-induced Ig response when both the GPE-1 and GPE-2 populations were removed on Day 1. Additional evidence for functional T-H cells in the GPE-rosetting population was obtained by analyzing interleukin-2 (IL-2) production. Removal of the GPE-rosetting cells (GPE-1 and/or GPE-2) from PBL led to a marked decrease in Con A-induced IL-2 synthesis while removal of the GE-rosetting cells yielded a normal or slightly greater than normal response.

Animals↗
PubMed1991

H-2K molecules positively select V beta 17a+ CD4(-)8+ T cells in bone marrow and thymic chimeras.

Population size of V beta 17a brightly positive cells among CD4(-)8+ thymocytes was analyzed in thymic chimeras as well as bone marrow (BM) chimeras in which SWR/J mice were used as BM donors and various strains of mice including H-2Kb mutant (bm) mice as recipients. It was shown that the proportion of V beta 17a+ CD4(-)8+ thymocytes was determined by H-2K molecules expressed on thymic epithelial cells. The highest proportion was observed in Ks and Kb thymuses, the intermediate proportion in Ks/q and Kk, and the lowest in Kq thymuses. Fine analysis of the H-2Kbm molecules involved in the positive selection revealed that the region important to the selection was located on the beta-pleated floor of antigen recognition site. According to the three-dimensional class I structure, this site appears not to be directly accessible to the T cell antigen receptor. Thus, the present finding suggests that the substitutions of amino acids at this site alter the shape and charge of the peptide binding site and eventually influence the positive selection of the V beta 17a+ T cell repertoire during differentiation.

Animals↗
PubMed1991

NZB serum factor (NZB-SF)-B precursor cell maturation factor. II. In vivo effects of NZB-SF or mAb against NZB-SF on B lineage cell populations.

In vivo effects of NZB serum factor (NZB-SF), which enhances the maturation of B precursor cells in vitro, were examined. Immunoaffinity-purified NZB-SF from young NZB mice was injected into B6 mice intraperitoneally twice weekly, five times total (5 micrograms/dose/mouse). Control mice were given 0.01% albumin. Then the B lineage cell populations defined phenotypically (sIg+ cells, B220+ cells, and AA4.1+ cells) or the numbers of colony-forming B lineage cells were examined. NZB-SF-treated B6 mice exhibited a decrease in the percentage of B precursor cells in marrow, even though the percentage of sIg+ cells in marrow or spleen did not differ from controls. In contrast, the frequency of colony-forming B cells in marrow and spleen, especially sIg- colony-forming B cells in marrow, increased significantly in NZB-SF-treated mice as compared to controls. In addition, monoclonal antibody (mAb) against NZB-SF was injected weekly for 9 weeks into NZB mice beginning at 7 weeks of age. mAb vs NZB-SF at a dose of 5 micrograms per mouse per injection, as stated above, prevented the decline of sIg- colony-forming B lineage cells which usually occurred in the adult NZB mice (greater than 16 weeks). This treatment also prevented, in part, the decline of the B220+ cell population which normally occurs in the marrow with increasing age. Thus NZB-SF impressively influences the composition of B lineage cell populations in normal B6 mice and may account for abnormal changes of B lineage cell populations observed in NZB mice.

Animals↗
PubMed1991

Soluble Fc epsilon R II levels in normal children and patients with immunodeficiency diseases.

CD23 is expressed on mature B cells and is identical to a low-affinity IgE Fc epsilon receptor type II (Fc epsilon R II). The C terminal portion of CD23 is released to the serum as soluble Fc epsilon R II (sFc epsilon R II), which may be involved in regulation of IgE synthesis. We studied sFc epsilon R II levels in normal children and in patients with immunodeficiencies, including common variable immunodeficiency (CVI), partial DiGeorge syndrome, and immunodeficiency associated with ectodermal dysplasia to examine the relationship of sFc epsilon R II levels to B cell numbers and other immunoparameters. Serum Fc epsilon R II levels are higher in younger children (younger than 3 years) and decline gradually with age. In 11 patients with CVI with normal numbers of B cells (greater than 6%), sFc epsilon R II levels were comparable to that of control subjects. Five patients with CVI with deficiencies of peripheral B cells had levels of sFc epsilon R II similar to levels of control subjects. In all but one patient with partial DiGeorge syndrome, sFc epsilon R II levels were not significantly elevated, despite the presence of elevated peripheral B cell numbers. Of six patients with ectodermal dysplasia, four demonstrated increased Fc epsilon R II levels, a finding not correlated with serum IgE levels or with peripheral eosinophil or B cell numbers.

Adolescent↗
PubMed1991

Specific association of retroviral envelope protein, p15E, with human cell surfaces.

Experiments were carried out to analyze the binding sites on human cells for highly purified retroviral protein p15E isolated from Feline Leukemia Virus, Rickard Strain. Binding of 125I-labeled p15E was tested with surfaces of human peripheral blood lymphocytes and 3 cell lines, Raji, MOLT-4, and U-937. 125I-labeled p15E showed specific binding to human peripheral blood lymphocytes. In addition, all of the cell lines tested showed binding of 125I-labeled p15E. Using U-937 cells, we characterized the interaction between p15E and the surface of these cells, and showed that the binding was specific by the following 3 different sets of evidence: (i) in equilibrium binding experiments, 18,000 binding sites with a dissociation constant of 2 x 10(-9) M were present on U-937 cells; (ii) trypsin or N-glycanase treatment decreased the binding sites of 125I-labeled p15E; and (iii) by affinity chromatography using p15E or BSA Sepharose columns, the isolated membranes of 125I-labeled U-937 cells previously treated with Triton X-100 showed a significantly higher binding to the p15E column than to the BSA column.

Amidohydrolases↗
PubMed1991

In vitro immunomodulation and in vivo immunotherapy of retrovirus-induced immunosuppression.

Early studies with the Gross passage A leukemia virus demonstrated that retroviral infection suppresses cellular and humoral immune responses. In extensive studies of the feline leukemia (FeLV) virus, which can induce profound immunodeficiency disease, are generative anemia and lymphoid, myeloid and erythroid neoplasia, the immunosuppressive effects of this retrovirus could be attributed to the actions of the retroviral envelope protein p15E. We found that a highly conserved, synthetic 17 amino acid peptide synthesized by Cianciolo and co-workers that is homologous to the hydrophilic portion of the otherwise hydrophobic transmembrane envelope protein can suppress polyclonal activation of B-cells, impair production of gamma- and alpha-interferon, inhibit production of interleukin-2, inhibit expression of IL-2 receptors, and suppress responses of cytotoxic lymphocytes. In analyses with inactivated preparations of the human immunodeficiency virus, with Pahwa et al. we demonstrated that purified non-infectious retrovirus and also retroviral proteins, in particular gp120, appeared to produce some of the immunosuppressive properties of HIV, particularly suppression of B-cell activation in response to known B-cell stimulants irrespective of T-cell influence, suppression of T-helper cell functions essential to B-lymphocyte responsiveness, and impaired function of immunoglobulin-secreting cells. Other investigators have also reported strong immunosuppressive or immunostimulatory influences for components of the HIV retrovirus and also gp120 through yet poorly elucidated but certainly complex actions on both T- and B-lymphocyte-mediated immune functions.

Animals↗
PubMed1991

Distribution of MEL-14+ cells in various lymphoid tissues.

The distribution of MEL-14+ lymphocytes was investigated by both fluorocytometric analysis and complement-dependent-cellular-cytotoxicity (CDCC) tests in which rabbit anti-rat Ig was added with complement at a secondary step. When CDCC was employed to detect MEL-14+ cells, almost half of the thymocytes were found to be MEL-14+ in various strains of mice. This high proportion of MEL-14+ cells stands in striking contrast to prior reports. Furthermore, when determined by fluorocytometric analysis, MEL-14+ cells were found to comprise more than 80% of the cells in the thymus. The MEL-14+ thymocytes comprised both immature subsets (CD4-8-, CD4+8+) and mature subsets (CD+8-, CD4-8+). MEL-14 brightly positive (MEL-14high) cells, however, were located mainly in mature T cell subpopulations within the thymus. The MEL-14high thymocytes appeared to be susceptible to the CDCC method. Most of MEL-14+ cells present in spleens and lymph nodes were shown to be included in the MEL-14high population. The MEL-14+ cells susceptible to treatment with MEL-14, rabbit anti-rat Ig plus complement in the spleen and lymph node were restricted to cells of the T-lineage. These data suggest that T cells may change from cells with low expression of the MEL-14 antigens at their surface to cells with high MEL-14 antigens in the process of differentiation. Furthermore, these findings indicate that MEL-14 molecules may be used as a surface marker to characterize an important T cell subpopulation.

Animals↗
PubMed1991

Studies of immunomodulating actions of carotenoids. I. Effects of beta-carotene and astaxanthin on murine lymphocyte functions and cell surface marker expression in in vitro culture system.

The immunomodulating effects of carotenoids (beta-carotene and astaxanthin) on mouse lymphocytes were studied in in vitro culture system by use of assay for mitogen responses of spleen cells, thymocyte proliferation, interleukin 2 production, and antibody (Ab) production in vitro in response to sheep red blood cells. Changes of cell surface markers on spleen lymphocytes including Ia antigen (Ag), surface immunoglobulin, B220, and Thy-1 Ag were also examined. At a concentration of 10(-8) M, carotenoids did not show any significant effect on mitogen responses (phytohemagglutinin P and concanavalin A) on murine spleen cells, irrespective of the concentrations of mitogens used. Interleukin 2 production by murine spleen cells was not significantly altered by carotenoids in the culture media (10(-7) to 10(-9) M). [3H]thymidine incorporation by B6 thymocytes was somewhat enhanced in the presence of astaxanthin or beta-carotene when cultured in the concentration of 10(6)/ml. At higher concentrations of cells (5 x 10(6)/ml), such an effect was not observed. In assays of in vitro Ab production in response to sheep red blood cells, B6 spleen cells produced significantly more Ab-forming cells (plaque-forming cells, immunoglobulins M and G) in the presence of astaxanthin (greater than 10(-8) M) but not beta-carotene. Expression of Ia Ag seemed to be moderately enhanced on both Thy-1+ and Thy-1- spleen cells in the presence of astaxanthin (greater than 10(-9) M) but not beta-carotene. The expression of Thy-1 and surface immunoglobulin seemed unchanged with the treatment of these carotenoids. These results indicate that immunomodulating actions of carotenoids are not necessarily related to provitamin A activity, because astaxanthin, which does not have provitamin A activity, showed more significant effects in these bioassays and also indicate that such actions of carotenoid demonstrated in this study may be difficult to explain only by its oxygen-quenching capacity.

Adjuvants, Immunologic↗
PubMed1991

Intravenous immunoglobulin therapy for chronic inflammatory demyelinating polyneuropathy recalcitrant to conventional therapy.

Chronic idiopathic demyelinating polyneuropathy is an immunologically mediated disorder that may not respond to glucocorticoid therapy, cytotoxic or other immunosuppressive medications, or plasmapheresis. We have reported such a case in which the patient had sustained clinical improvement with the repeated administration of high doses of intravenous immunoglobulin.

Chronic Disease↗
PubMed1991

Detection of human factor B biosynthesis in culture supernatants and cell lysates by ELISA.

We report here on the development of a simple, sensitive, convenient, and quantitative enzyme-linked immunosorbent assay for human factor B, a protein of the alternative complement pathway, by the sandwich method using goat anti-human factor B antibody. The assay described herein is reproducible and highly specific for human factor B. The assay was used to determine biosynthesis (cell lysates or extracts) and secretion (supernatants) of human factor B using human monocyte cell line U937. Phorbol myristate acetate strongly enhanced (10- to 20-fold) biosynthesis of factor B by U937. The combination of a sensitive enzyme-linked immunosorbent assay and phorbol myristate acetate enabled us to use a microculture system.

Antimetabolites↗
PubMed1991

Zinc depletion modifies CD5 expression by 70Z/3 murine pre-B leukemia cell line.

CD5 expression on B cells is regulated by certain humoral factors. In a pre-B leukemia cell line 70Z/3, we found that interleukin 4 down-regulates it. Herein, we report that zinc influences spontaneous CD5 expression by this cell line as well as actions of these factors on CD5 expression considerably. In zinc-depleted culture media, spontaneous CD5 expression by 70Z/3 cells was enhanced. In contrast, the down-regulatory action of interleukin 4 was significantly reduced under culture conditions of zinc depletion. The supplementation of zinc to physiologic concentrations (1 to 2 microM) abolished such effects of zinc-depleted medium. The reduction of the suppressive action of interleukin 4 was observed at the level of gene expression. However, CD5 mRNA expression enhanced by lipopolysaccharide or NZB-SF was not further enhanced under conditions of zinc deficiency. These observations may suggest that CD5 expression by malignant or even normal B cells may be influenced by cellular/serum zinc levels.

Animals↗
PubMed1991

Long-term immunologic tolerance induction in chimeric mice after bone marrow transplantation across major histocompatibility barriers: persistent or redeveloping immunologic responsiveness after prolonged survival.

Employing allogeneic bone marrow chimeras [B6----C3H] (C3H/HeN mice lethally irradiated and then reconstituted with T cell-depleted C57BL/6J bone marrow), we investigated the kinetics of immunological reconstitution and the functional characteristics of the immune system at regular intervals following bone marrow transplantation (BMT). In chimeric mice, almost all spleen cells and peritoneal macrophages showed donor H-2 haplotype within 2 weeks after BMT. The differentiation and maturation of B lymphocytes and macrophages was largely complete by 2 weeks following BMT, whereas T cell functions such as Con A responsiveness and alloreactivity were not restored within 4 weeks. Newly developed T cells were found to be exclusively of donor origin but were tolerant of both donor type and host type major histocompatibility complex (MHC) determinants in assays of mixed lymphocyte reactions and capacity to generate cytotoxic T lymphocytes. Fully allogeneic chimeric mice survived up to one year after bone marrow transplantation without significant reactions or serious diseases. Neither graft-versus-host reaction (GVHR), host-versus-graft reaction (HVGR), nor the wasting diseases described. As compared to age-matched control mice, such fully allogeneic chimeras exhibited one year following BMT somewhat reduced but quite significant plaque forming cell responses to in vitro stimulation with a T-dependent antigen, SRBC. These findings suggest that BMT across MHC barriers may ultimately be useful in humans if all manifestations of GVHR are eliminated by completely removing all T cells from the bone marrow and if all hematopoietic resistance and all aspects of HVGR are eliminated by using sufficient immunosuppression and myeloablation.

Animals↗