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Biomedical subjects

M D Cooper

Publications and source records attributed to M D Cooper.

At least 325 records · Page 18Linked to original sources
PubMed1981

Developmental changes in heart and muscle phosphofructokinase isozymes.

Phosphofructokinase isozymes of fetal, neonatal, and adult rat heart and skeletal muscle were characterized by DEAE-cellulose chromatography, agarose gel electrophoresis, and immunodiffusion with specific antisera. The results of these studies indicate that in skeletal muscle and heart the levels of the major liver phosphofructokinase isozyme (PFK-L2) and the muscle phosphofructokinase isozyme (PFK-M) are dependent on the developmental status of the rat. For example, PFK-L2 and PFK-M are present in fetal and early neonatal skeletal muscle; whereas in adult skeletal muscle, only PFK-M is detectable. By DEAE- cellulose chromatography, PFK-L2 activity was estimated to be 2.4 units/g (41% of total phosphofructokinase activity) in fetal muscle, very low and not resolved from PFK-M in 7-day neonatal muscle, and not detectable in adult muscle. Further, PFK-M activity was found to be 3.4 units/g (59% of total phosphofructokinase activity), 10 units/g, and 31.6 units/g in fetal, 7-day neonatal, and adult skeletal muscle, respectively. The developmental changes of heart phosphofructokinase isozymes differ considerably from that of the skeletal muscle phosphofructokinase isozymes. In fetal heart, PFK-L2 is the major phosphofructokinase isozyme (5.6 units/g), constituting 67% of total phosphofructokinase activity. Further, in fetal heart another phosphofructokinase isozyme (33% of total phosphofructokinase activity) was found by DEAE-cellulose chromatography which is different from PFK-M and PFK-L2. In 7-day neonatal and adult heart, PFK-M and PFK-L2 are the only detectable phosphofructokinase isozymes. Varying from 5.6 units/g (44% of total) in 7-day neonatal to 5.9 units/g (40% of total) in adult heart, PFK-L2 activity remains fairly constant. Also, PFK-M is very low in fetal heart but increases within 1 week postpartum to 5.5 units/g (50% of total activity) and to 8.9 units/g (60% of total activity) in adult heart.

Aging↗
PubMed1981

Diversity of immunoglobulin expression in leukaemic cells resembling B-lymphocyte precursors.

Approximately 20% of patients with acute lymphocytic leukaemia (ALL) have leukaemic blasts with features of pre-B cells which are the recently characterized precursors of B lymphocytes in normal development (for a review, see ref. 2). Pre-B cells isolated from normal bone marrow or fetal liver, and malignant cells from patients with pre-B cell leukaemia, are rapidly dividing lymphoid cells that contain cytoplasmic immunoglobulin mu heavy chains, but have no detectable surface immunoglobulin. The resemblance of immunoglobulin-containing ALL cells to normal precursors of B lymphocytes and their availability in relatively pure preparations allowed us to explore them as models of early stages in the differentiation of the B-lymphocyte line. We report here observations on the occurrence of intermediate pre-B/B-cell phenotypes, immunoglobulin isotype switching and the asynchrony of immunoglobulin heavy and light chain expression in 30 cases of ALL and 3 cases of chronic myelogenous leukaemia in lymphoblastic crisis (CML-BC).

B-Lymphocytes↗
PubMed1981

Immunofluorescence studies on the expression of VH a allotypes by pre-B and B cells of homozygous and heterozygous rabbits.

Fluorochrome-conjugated antibodies specific for C mu determinants and VH a allotypes were used to examine pre-B cells and B lymphocytes for expression of these markers. The majority of mu+ bone marrow pre-B cells were shown to express a allotypic determinants in conjunction with C mu. Both pre-B and B cells from a2 a3 heterozygous rabbits showed allelic exclusion of these allotypes. Pre-B cells expressing the a2 or a3 specificities appeared to be generated in approximately equal numbers in heterozygotes, while B lymphocytes expressing a3 appeared to undergo preferential clonal expansion very early in development. It was also observed that rabbit bone marrow and blood contained a population of myeloid cells which, in a2 a3 heterozygotes, stained for both a2 and a3 determinants. The frequencies of this cell type, which exhibited bright immunofluorescence staining for a allotypes, could not be reduced by prolonged incubation at 37 degrees C but were readily reduced after cell suspensions were treated with low pH buffer. It is concluded that these myeloid cells bear high avidity Fc receptors for serum immunoglobulin and may be the culprits in studies which have found production of two a or b allotypes by individual B lymphocytes.

Animals↗
PubMed1981

Pre-B cells; normal and abnormal development.

The immediate precursors of B lymphocytes have been recently identified in fetal liver and in bone marrow. Immunoglobulin genes, first of the heavy-chain gene family and later from one of the light-chain gene families, are selected and undergo functional rearrangements on one of each chromosomal pair during this stage of differentiation. Thus clonal diversity is generated among cycling pre-B cells that lack the surface antibody expression which characterizes their B-cell progeny. While the number of discriminating markers for pre-B cells is still limited, examination of bone marrow pre-B cells containing cytoplasmic mu chains but lacking surface immunoglobulin has already revealed an informative spectrum of early differentiation defects in antibody deficiency diseases and malignancies of B lineage.

Animals↗
PubMed1981

Immunoregulatory defects in a family with selective IgA deficiency.

Defects in regulation of the humoral immune system were examined in a family with selective IgA deficiency. Two patients (mother and son) were clinically well and had selective abnormalities of B lymphocytes that can differentiate into IgA plasma cells plus specific T cell suppression of IgA production. One patient (daughter) had several clinical problems and received nine monthly transfusions of normal plasma. Prior to therapy, this patient had abnormal immunoregulation of both B and T lymphocyte population that cooperated in the formation of all cases of immunoglobulin-producing cells. After treatment, her clinical problems were resolved and her cellular abnormalities appeared identical in those in her mother and brother.

Adolescent↗
PubMed1981

Role of outer envelope contamination in protection elicited by ribosomal preparations against Neisseria gonorrhoeae infection.

A recent report (Cooper et al., Infect. Immun. 28:92-100, 1980) demonstrated that immunization of guinea pigs with ribosomal preparations was protective (approximately 90%) against chamber infections with Neisseria gonorrhoeae. Similar protection has been demonstrated with other cellular immunogens such as outer membranes (OM) (92%) or purified lipopolysaccharide (LPS) (83%). Protection of LPS (5 to 100 micrograms) was dose dependent (83% with 100 micrograms). Treatment of LPS with pronase reduced the protection by 50%. Ribosomal preparations contained LPS contamination (3.9%) based on dry weight determinations by 2-keto-3-deoxyoctonate analysis. Analysis of ribosomal preparations isolated from cells after lactoperoxidase-mediated 125I labeling indicated a major OM contamination (Protein I). The ribosomal preparation also contained low levels of succinic and lactic dehydrogenase. Passive hemagglutination tests revealed that sera from guinea pigs immunized with ribosomal preparations also demonstrated antibody to OM proteins and LPS. LPS was able to absorb one line of precipitation seen in immunodiffusion reactions as well as the bactericidal activity of such sera. OM preparations were unable to absorb the remaining precipitin line or remove the bactericidal activity. It appears that LPS is the major antigen responsible for the bactericidal activity seen in ribosome-immune sera.

Absorption↗
PubMed1981

Abnormalities of T cell maturation and regulation in human beings with immunodeficiency disorders.

A series of monoclonal antibodies to T cell surface antigens were used to characterize peripheral lymphoid populations from patients with a variety of immunodeficiency diseases. Several disorders of T cell differentiation were observed to occur in severe combined immunodeficiency. One subtype of severe combined immunodeficiency was associated with failure to develop lymphocytes that express any thymus specific antigens, another with failure to differentiate beyond the early prothymocyte-thymocyte (T9+, T10+) stage, while a third subtype was associated with failure to differentiate beyond a late thymocyte (T3+, T4+, T5+/T8+, T10+) stage. In contrast, patients with thymic aplasia (DiGeorge syndrome) had a diminished but detectable population of mature T cells. Imbalances in immunoregulatory T cells with a relative excess of suppressor cells were found in 9 of 17 patients with spontaneously occurring acquired agammaglobulinemia. In one of the latter individuals, there was an activated suppressor T cell population expressing Ia antigens (T+/T8+, Ia+). Another had no inducer T4+ cells. Patients with X-linked agammaglobulinemia frequently had an abnormal ratio of inducer to suppressor cells as well as an absence of circulating surface immunoglobulin-bearing cells. No such abnormalities were noted in normals or individuals with selective immunoglobulin (Ig)A deficiency. Taken together, these findings support the notion that several immunodeficiency states may occur as a consequence of defective T cell maturation or imbalances in immunoregulatory T lymphocyte subpopulations.

Adolescent↗
PubMed1981

An analysis of clinical and laboratory features of acute lymphocytic leukemias with emphasis on 35 children with pre-B leukemia.

In 35 of 191 patients with acute lymphocytic leukemia (ALL) malignant cells were similar in phenotype to B-lymphocyte precursors. Both these patients' lymphoblasts and normal pre-B-cells contain cytoplasmic immunoglobulin (Ig) mu heavy chains, but have no surface Ig. In patients with pre-B leukemias, lymphoblasts containing cytoplasmic mu chains alone were often accompanied by cells of identical morphology that expressed no Ig and less frequently by lymphoblasts bearing scant amounts of surface mu. This spectrum of cellular Ig expression suggests that "null," pre-B, and intermediate pre-B/B ALLs represent closely related malignancies with complete or partial arrests at different stages of maturation. When pre-B, B, T, and "null" cell categories of ALL were compared for 22 different clinical and laboratory features, including remission rate and short-term remission duration, no statistical differences were observed between the pre-B and "null" groups. These early results suggest that pre-B-cell leukemias represents a relatively good prognostic subclass of ALL, do not require more intensive treatment than that proven to be effective for "null" cell ALL, and should be distinguished from the less common, but more clinically aggressive, B-cell subclass of ALL. Longer follow-up will be required to confirm these preliminary conclusions.

B-Lymphocytes↗
PubMed1980

Human T lymphocyte subpopulations defined by Fc receptors and monoclonal antibodies. A comparison.

Human T cell subpopulations have been defined on the basis of differential expression of either Fc receptors or specific cell-surface antigens. In this study, we utilized a series of monoclonal antibodies reactive with T cells, monocytes, and Ia antigens to characterize isolated subpopulations of T cells bearing receptors for the Fc portion of IgG (T gamma) and subpopulations of T cells bearing receptors for the Fc portion of IgM T mu. The results showed that the T mu population contained both inducer (OKT4+) and cytotoxic/suppressor (OKT5+) populations and was similar to the unfractionated T cell population, whereas the T gamma subset contained few T lymphocytes (OKT3+) and was not enriched for either T cell subset defined by these monoclonal antibodies. Rather, the T gamma population was comprised largely of Ia- cells possessing a monocyte antigen (OKM1+). In reciprocal studies, it was found that both isolated OKT4+ and OKT5+ T cell subsets contained few T gamma cells, whereas both subsets were mainly comprised of T mu cells. We conclude that there is little correlation between T cell subsets defined by these monoclonal antibodies and those defined by Fc receptors.

Antibody Specificity↗
PubMed1980

Genetics of Ia-like alloantigens in chickens and linkage with B major histocompatibility complex.

Two sets of backcross matings were performed to test for linkage between genes coding for the Ia-like antigens ("Ia") and the B erythrocyte antigens (Ea-B) of the chicken. Evidence is presented which indicates that the "Ia" antigens are determined by a single codominant locus and that the Ea-B and "Ia" loci are on the same chromosome. Failure to detect a single recombinant between the Ea-B and "Ia" loci out of 208 progeny suggests close linkage of the two genes with a map distance of up to about 2 centimorgans. The "Ia" genes are thus included in the B major histocompatibility complex of the chicken.

Animals↗
PubMed1980

Mouse pre-B cells synthesize and secrete mu heavy chains but not light chains.

The immunoglobulins produced by the earliest recognizable B cell precursors (pre-B cells) were characterized in the mouse and human. Immunofluorescent analysis revealed no evidence of surface IgM components, and only mu heavy chains could be detected intracytoplasmically in pre-B cells. Surface IgM components could not be isolated from intact fetal liver cells that lacked sIgM+ B lymphocytes but possessed pre-B cells. Pre-B cells were shown to synthesize and secrete mu heavy chains but not light chains by immunochemical analysis. These mu chains constituted less than 0.01% of TCA precipitable protein synthesized and secreted by fetal liver cells during an 8 hr labelling period. Migration of both intracellular and secreted mu chains on SDS-PAGE suggested that they were smaller than mu chains secreted by mouse and human plasmacytomas. These data indicate that mu chain synthesis precedes light chain expression during B cell ontogeny and suggest a new role for pre-B cells in the generation and expression of a diverse immunoglobulin repertoire.

Agammaglobulinemia↗