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Biomedical subjects

R A Good

Publications and source records attributed to R A Good.

At least 379 records · Page 21Linked to original sources
PubMed1983

Transplantation for severe combined immunodeficiency with HLA-A,B,D,DR incompatible parental marrow cells fractionated by soybean agglutinin and sheep red blood cells.

Three patients with severe combined immunodeficiency (SCID) received transplants of HLA haplotype-mismatched parental bone marrow depleted of T lymphocytes by differential agglutination with soybean agglutinin (SBA) and subsequent E-rosette depletion. Two patients achieved durable engraftment with reconstitution of both humoral and cell-mediated immunity. Neither of these patients developed graft versus host disease (GVHD). The third patient achieved only a transient engraftment with concomitant development of mitogen-responsive lymphocytes of paternal origin. Our experience indicates that depletion of T lymphocytes by this technique can abrogate the potential of histoincompatible marrow grafts to induce lethal GVHD without limiting immunologic reconstitution. It also provides further evidence of nonimmune mechanisms of graft resistance that may necessitate preparative treatment of patients with SCID before transplantation with HLA-mismatched marrow cells.

Bone Marrow Transplantation↗
PubMed1983

Functional maturation difference between splenocytes that form autologous rosettes in adult thymectomized and aged mice.

Thymic hormones induce changes in surface markers and functions in precursors of T cells during maturation. In previous studies, thymopoietin32-36 (TP-5) was found to influence maturation of immature splenocytes characterized by their ability to form autologous rosettes (A-RFC) and bind peanut agglutinin (PNA). These immature cells were increased in numbers in the spleen of nu/nu mice, adult thymectomized animals (ATx) and aged mice, which lack thymic factor activity in serum. Following in vitro exposure to TP-5, reduction in the number of A-RFC and splenocytes bearing receptors for PNA was observed while a small number of cells, which did not possess Thy-1.2 antigen originally, acquired this phenotype. However, it remained to be determined whether these surface changes were equivalent to T-cell differentiation. The present study was undertaken to clarify whether changes in surface receptors influenced by thymic hormones in vitro are associated with changes in cellular functional activities. Under the influence of facteur thymique sérique (FTS), maturation of isolated populations of immature splenocytes (A-RFC+) from ATx mice and aged animals was accompanied by loss in ability to form autologous rosettes but acquisition of a functional activity was observed only in splenocytes from ATx mice and not in those from aged mice.

Aging↗
PubMed1983

Circulating thymic hormone levels in severe combined immunodeficiency.

Twenty-three patients with severe combined immunodeficiency disease were studied for circulating thymic hormone levels (facteur thymique serique, FTS), 21 prior to treatment by transplantation of bone marrow, thymus or fetal liver. Thirteen showed undetectable FTS activity. Only two had normal levels of this hormone. In serial determinations of FTS activity prior to and after transplantation, patients given bone marrow transplants developed sustained increments of serum FTS activity early in the course of their immunological reconstitution. However, patients given transplants of fetal liver alone or fetal liver plus thymus from fetuses of less than 12 weeks gestation generally did not show an increment of FTS activity during the period of observation. Transplantation of irradiated thymus derived from fetuses of more than 14 weeks gestation produced sustained increases of thymic hormone activity. These observations suggest that a cell of haematopoietic origin provides a stimulus necessary for differentiation or maturation of thymic secretory activity and that this cell(s) is present in post-natal marrow, but is either undeveloped or immature in the early fetal liver or fails to migrate to the thymus of an allogeneic host.

Antibody Formation↗
PubMed1983

B lymphocyte lineage cells in newborn and very young NZB mice: evidence for regulatory disorders affecting B cell formation.

As adults, NZB mice have a severe deficiency of identifiable precursors of B lymphocytes, but this is preceded by a time when B cells and their immediate precursors are present in bone marrow in elevated numbers. Our present studies indicate that the final stages of B cell formation may be proceeding at a greater than normal rate at 4 wk of age. At this time, large numbers of sIg- B cell precursors can be identified in NZB but not in normal CBA/H or DBA/2 marrow that can respond to mitogens in semisolid agar cultures without preculture. Colony formation by these precursors was dependent on the presence of Sephadex G-10-adherent cells in the suspensions. In this respect, 4-wk-old NZB marrow was similar to spleen and liver of normal CBA/H newborn mice. Mixing experiments suggested that hyperactive regulatory cells present in young NZB marrow may promote functional maturation of normal pre-B cells from CBA/H or DBA/2 mice. In addition, potent substances present in the serum of young but not older NZB mice produced the same effect. Factor-mediated enhancement of clonal proliferation by sIg- precursors was not dependent on adherent cells and required more than brief exposure of the cells to young NZB serum. These are all indications that abnormalities of B lineage differentiation in young NZB marrow may be attributable to microenvironmental elements. Congeneic, B cell-deficient NZB.xid mice, however, lacked hyperactive regulatory cell function and serum factors that characterize NZB mice of this age. A study was also made of B cell precursors in newborn spleen and liver of NZB mice, and abnormal shifts of populations of B lineage cells were already present by that time. These observations support previous contentions that humoral immunity is precocious and abnormally regulated in NZB mice.

Aging↗
PubMed1982

Age-dependent deficiency of B lymphocyte lineage precursors in NZB mice.

Adult NZB mice (greater than 15 wk old) have very few bone marrow cells that can give rise to sIg+ clonable B cells during liquid culture. This deficiency corresponds to extremely low numbers of cells with cytoplasmic but not surface mu chains of IgM and reduced numbers of cells bearing a high molecular weight B-lineage antigen. Depletion of Thy-1-bearing cells and appropriate mixing experiments did not provide evidence either that suppressor cells are responsible for this phenomenon or that accessory cells are defective in NZB mice. Nor did it seem that B cells were being produced in extramedullary sites. B cell precursors were detectable in very young NZB mice, exceeded control values at 4-5 wk of age, and then declined rapidly. In contrast, these persisted for greater than 1 yr in normal BALB/c, DBA/2, and CBA/H mice. It appears possible that intermediate stages in B-lineage differentiation become prematurely exhausted through an accelerated aging process in NZB mice. These chronological changes have implications for understanding the sequence of events that lead to B lymphocyte formation and the processes that normally regulate it.

Aging↗
PubMed1982

Cell-free translation of the messenger RNA for calf terminal deoxynucleotidyltransferase.

Poly(A)-rich RNA has been isolated from calf thymus and translated in vitro in a rabbit reticulocyte translation system. Three peptides with Mr = 58,000, 33,000, and 13,000 were specifically immunoprecipitated from the translation products with calf terminal deoxynucleotidyltransferase antiserum. An oligo(dT)-purified preparation of calf terminal transferase competed with only the Mr = 58,000 peptide in the immunoprecipitation reaction. The anti-terminal transferase serum did not precipitate a Mr = 58,000 peptide from translation products of spleen or liver mRNA, but it did precipitate the Mr = 33,000 and 13,000 peptides from products of spleen mRNA and a Mr = 13,000 peptide from products of liver mRNA. In addition, when an affinity-purified antibody to calf terminal transferase was used, only a Mr = 58,000 peptide was immunoprecipitated from the translation products of calf thymus mRNA, and none was immunoprecipitated from spleen or liver mRNA products. This antibody also precipitated a Mr = 58,000 peptide from the cell lysates of calf thymocytes labeled in vitro with [35S]methionine. These results demonstrate that calf terminal transferase is biosynthesized as a Mr = 58,000 peptide.

Animals↗
PubMed1982

Specific elimination of the T lineage cells: effect of in vitro treatment with anti-Thy 1 serum without complement on the adoptive cell transfer system.

Thymocytes from C57BL/6(B6) mice treated with anti-Thy 1 antiserum without complement in vitro were transferred to lethally irradiated AKR mice. Five days following transfer, the proportion of Thy 1.2(+) cells recovered from the recipient spleen was significantly lower (7%) than that from the control mice which had received untreated cells (64%). the B6 spleen cells were treated in the same manner and transferred with SRBC (T-dependent antigen) or DNP-Ficoll (T-independent antigen) to irradiated syngeneic recipients. The recipients developed a response to SRBC which was significantly lower than that observed in control mice, but showed the same number of plaque-forming cell (PFC) against TNP-SRBC as the control group of mice which had received untreated B6 spleen cells. These results clearly show that in vitro pretreatment of lymphocytes with anti-Thy 1 serum without complement specifically resulted in elimination or inactivation of the T lineage cells in the host environment. The mechanisms of the elimination are discussed in this study.

Animals↗
PubMed1982

IgA antibody to spermatozoa in seminal and prostatic fluids of a subfertile man.

the mechanism of spontaneous sperm agglutination in the ejaculate of a subfertile man was investigated. Using enzyme-linked immunosorbent assays it was found that the patient's spermatozoa had a mean of 2.3 times more IgA bound to it than did spermatozoa from fertile men. IgA antibody to spermatozoa was also found in the patient's seminal fluid and prostatic fluid, but not in his serum. In this patient it appeared that agglutination was due to an IgA antibody to spermatozoa that was produced locally within the genital tract.

Adult↗
PubMed1982

Antibody-independent complement activation by myelin via the classical complement pathway.

Murine or rabbit whole brain homogenates were shown to activate human complement via the classical pathway by an antibody-independent reaction. This activity required Ca++ ions. Anticomplementary activity in fractionated murine brain was found to reside in the myelin fraction and in purified myelin. It was absent, however, both from highly purified myelin basic protein (MBP) and from the MBP-free residue. Because purified MBP is a monomer and this protein exists in brain tissue largely as a dimer, the ability of the cross-linked form of MBP to activate complement was investigated. MBP, dimerized with difluorodinitrobenzene, was highly anticomplementary. The murine brain, inactive when taken from the newborn mouse, was shown to first acquire the capacity to activate complement at 7 d after birth. This finding is consistent with the report that the synthesis of myelin protein has been shown to be initiated in murine brain 8 d after birth. Complement activation by MBP could play an important role in the pathological changes observed in neurological disorders.

Animals↗