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Biomedical subjects

J F Kearney

Publications and source records attributed to J F Kearney.

At least 127 records · Page 7Linked to original sources
PubMed1982

Immunoglobulin isotype expression of normal pre-B cells as determined by immunofluorescence.

We have undertaken an immunofluorescent analysis of the immunoglobulin heavy and light chains expressed by pre-B cells from normal human fetal and adult bone marrow using purified mouse monoclonal and goat antibodies to human immunoglobulin isotypes. Our results indicate that (i) the great majority of normal pre-B cells in both fetuses and adults expresses intracytoplasmic mu chains only, (ii) immunoglobulin light-chain synthesis may be initiated during a late stage in pre-B-cell development, and (iii) heavy-chain isotype switching at the pre-B-cell stage may not occur during normal B-cell development.

Adult↗
PubMed1982

Demonstration of calcium-induced conformational change(s) in C-reactive protein by using monoclonal antibodies.

Three out of four anti-C-reactive protein monoclonal antibodies [HB3-2, (micro, k)], EA4-1 (gamma 2a, k) and FB2-1 (gamma 1, k) bind to C-reactive protein in the presence of 2.5 mM Ca2+ but not in the presence of 1.0 mM EDTA, indicating that the conformation of the antigenic determinant(s) recognized by these three antibodies is dependent upon Ca2+. This Ca2+-dependent binding can be inhibited by 1.0 mM phosphocholine, indicating that this antigenic determinant is at or near the phosphocholine-binding site of C-reactive protein. The binding of the fourth monoclonal antibody [HD2-4 (gamma 2-k)] is independent of the presence of Ca2+ and is not inhibited by phosphocholine. HB3-2 (micro, k) recognizes an antigenic determinant on the structurally related proteins, rabbit CRP and serum amyloid P.

Antibodies, Monoclonal↗
PubMed1982

CRP-associated determinant expressed by human monocytes.

Reports of a large number of biological activities of the acute phase reactant C-reactive protein (CRP) (1,2) and its association with a variety of blood borne cells (3,4), led us to a study of the expression of CRP by human peripheral blood cells (PBL) using two kinds of CRP-reactive monoclonal antibodies. We had previously described a reaction of CRP with a monoclonal antiidiotype antibody to a murine phosphocholine (PCh) binding myeloma protein (5). Of another group of monoclonal antibodies obtained by immunizing mice with human CRP, three were shown to react with human CRP in a Ca++-dependent manner while a fourth reacted with CRP independently of calcium and binding of this antibody was also not blocked with PCh (6). Initial experiments showed that one of these site specific antibodies also reacted with a proportion of normal human peripheral blood cells. We then showed that this subpopulation included 100% of human monocytes suggesting that a CRP-like determinant exists on the surface of human monocytes but not on other lymphoid or NK cells or granulocyte populations.

Animals↗
PubMed1982

Estimate of the light chain repertoire size of fetal and adult BALB/cJ and CBA/J mice.

The potential light chain repertoires expressed by IgM antibodies of fetal liver and adult spleen cells were compared. B cells from these sources were stimulated by the polyclonal mitogen bacterial lipopolysaccharide and after 3 days were fused to construct hybridomas. The light chains synthesized by these hybridomas were isolated by electrophoresis and their heterogeneity was examined by isoelectric focusing. A total of 109 BALB/c and 77 CBA/J hybridoma-derived light chains obtained from fetal liver and adult spleen cells were analyzed in this way. Fifty-three and 45 unique light chains were obtained from BALB/c and C57BL/6 hybridomas, respectively. Some of these were repeated more frequently than others, but no significant differences were seen in the heterogeneity of the light chain spectrotypes of fetal and adult CBA/J and BALB/cJ mice. Furthermore, the kappa:lambda ratio of light chains were the same in fetal liver as adult-derived hybridomas. These results show that the heterogeneity of light chains as determined by IEF and the kappa:lambda ratio of IgM immunoglobulins is established very early in ontogeny.

Aging↗
PubMed1982

Human blood monocytes and platelets share a cell surface component.

We describe a surface determinant shared by human monocytes and cells of the megakaryocytic axis that has been identified using a mouse monoclonal antibody. This monocyte-platelet antigen (MPA) is expressed on all (greater than 99%) of peripheral blood monocytes, platelets, and megakaryocytes. It is also expressed weakly on the monocytic cell line U937 and the promyelocytic line HL60 and is present on cells from 3 of 4 AML patients examined. It is absent from polymorphonuclear leukocytes, T and B lymphocytes, erythrocytes, and a panel of hematopoietic cell lines. MPA is stripped from monocyte membranes with pronase and is reexpressed overnight. The determinant is carried on a noncovalently linked biomolecular complex with molecular weights of 93,000 and 135,000.

Animals↗
PubMed1982

Studies on the clonal origin of human B cell leukemia using monoclonal anti-idiotype antibodies.

The clonal origin of an IgA1 kappa B cell leukemia in a 71-year-old man (WF) was examined using a monoclonal anti-Id antibody and a panel of monoclonal anti-VH antibodies. Immunofluorescent studies revealed that all surface IgA1 kappa + leukemic cells in WF's blood and 10% of the IgM+ B cells in his bone marrow expressed the WF Id. Three percent of the IgA1 kappa + leukemic cells in blood also expressed gamma-chains in their cytoplasm. Approximately 0.1%, 1%, and 10% of bone marrow mononuclear cells, respectively, expressed mu-chains, gamma-chains, and alpha-chains in their cytoplasm, but no detectable light chains or surface immunoglobulins. These mu, gamma, and alpha-positive cells had the convoluted nucleus and narrow cytoplasm characteristic of normal mu+ pre-B cells. Sequential isotype switching among this unusual pre-B population was indicated by co-expression of mu-chains and alpha-chains by 11% and 63%, respectively, of the gamma pre-B cells. These pre-B cells and the surface alpha-chains and cytoplasmic gamma-chains of the leukemic B cells were reactive with one of four monoclonal anti-VH antibodies. The data suggest malignant transformation of the clone before isotype switching, and also imply light chain precommitment at the pre-B cell level of differentiation.

Aged↗
PubMed1982

Anti-DNA autoantibodies in (NZB X NZW)F1 mice are clonally heterogeneous, but the majority share a common idiotype.

Monoclonal anti-DNA antibodies from 13 cloned hybridoma cell lines have been used to analyze the clonal heterogeneity of autoimmune anti-DNA antibodies. The hybridomas were obtained by fusing spleen cells from a single, autoimmune (NZB X NZW)F1 mouse. With the use of the criteria of isotype, isoelectric focusing patterns, fine specificity for various nucleic acids, and idiotype, the monoclonal anti-DNA antibodies were found to be heterogeneous in that 12 different clonotypes were identified among the 13 monoclonal antibodies studied. However, eight out of the 13 monoclonal antibodies have similar antigen specificity and share a common idiotype. This suggests that although autoimmune anti-DNA antibodies within a single (NZB X NZW)F1 mouse are the products of a large number of different antibody-producing clones, many of the clones produce antibodies with similar antigen-binding regions. Furthermore, in the majority of (NZB X NZW)F1 mouse sera the appearance of detectable levels of the common idiotype coincides with the appearance of anti-DNA autoantibody.

Animals↗
PubMed1981

Cross-reactivity between C-reactive protein and idiotypic determinants on A phosphocholine-binding murine myeloma protein.

Binding of human 125I-C-reactive protein (CRP) to sheep erythrocytes sensitized with pneumococcal C polysaccharide (E-PnC) was found to be Ca++ dependent and inhibitable by phosphocholine, CRP, and HOPC 8. Binding of 125I-HOPC 8 to EPnC was Ca++ -independent but could also be inhibited by phosphocholine, CRP, and HOPC 8. Thus, CRP and HOPC 8, despite a differential Ca++ requirement, share a common binding specificity for phosphocholine. A monoclonal anti-idiotypic antibody (MAB), GB4-10, prepared in A/J mice immunized with BALB/c HOPC 8 inhibited the binding of both 125I-CRP and 125I-HOPC 8 to E-PnC. In addition, both proteins bound to GB4-10 immobilized on polysterene tubes. Interestingly, binding of 125I-CRP to GB4-10 required Ca++. Similar results were also obtained with another MAB (AB1-2) prepared similarly to GB4-10, whereas neither protein bound to a control MAB (EB3-7) against an alpha1 leads to 3 dextran-binding myeloma protein, J558. Binding of 125I-HOPC 8 to GB4-10 could be inhibited by HOPC 8, keyhole limpet hemocyanin-phosphocholine but not phosphocholine but not phosphocholine, and in the presence of Ca++ by CRP. These data indicate that CRP bears antigenic determinants cross-reacting with certain idiotypic determinants on HOPC 8. They also suggest that Ca++ acts as an allosteric effector, perhaps stabilizing the phosphocholine-binding site of CRP.

Animals↗
PubMed1981

Monoclonal vs. heterogeneous anti-H-8 antibodies in the analysis of the anti-phosphorylcholine response in BALB/c mice.

Biological activities of monoclonal A/J antibodies to the T15 idiotype in BALB/c mice were compared to heterogeneous antibodies raised by conventional immunization procedures. Two monoclonal antibodies, AB1-2 and GB4-10, which are of the gamma 1, chi class, appeared to have identical specificities by binding criteria and reacted similarly to conventional antibodies in their abilities to induce neonatal suppression, inhibit plaque-forming cell induction by phosphorylcholine (PC) antigens and to inhibit specifically, anti-PC plaque-forming cells. However, in functional analyses of anti-PC responses in various strains of mice, discrepancies were noted in the T15 responses as defined by monoclonal antibodies and conventional antisera. This heterogeneity was also observed in adult mice suppressed with the GB4-10 monoclonal antibody. These animals eventually produced an anti-PC responses of AB1-2 idiotype but lacking the GB4-10 marker. These results show that the T15 IgM anti-PC response in BALB/c and other strains of mice is heterogeneous and probably consists of a family of clones. Particular clones can be precisely eliminated by the use of appropriate monoclonal antibodies, and the anti-PC response that eventually recovers is still T15+ but lacking the suppressed clones.

Animals↗
PubMed1981

Organization and expression of immunoglobulin genes in fetal liver hybridomas.

The organization and expression of immunoglobulin genes were studied in a series of six hybridomas derived from the fusion of a nonproducing myeloma cell with cells from mouse fetal liver. These hybridomas, which exhibit several phenotypic characteristics of immature B lymphocytes, all have productively rearranged mu heavy chain genes and produce both the membrane and secreted forms of mu mRNA in a ratio of about 1:10. Significantly, none of the hybridomas has an unrearranged (germ line) allelic mu gene. Examination of the kappa light chain genes revealed that all six of the hybridomas contain unrearranged kappa loci and produce 8.4-kilobase transcripts containing kappa constant region sequences. None of the five hybridomas that exhibit a mu-only phenotype contains a rearranged kappa gene other than that derived from the myeloma parent. One hybridoma, which actively secretes kappa immunoglobulin, contains a rearranged kappa gene of fetal liver origin and synthesizes a distinctive kappa mRNA precursor in addition to the 8.4-kilobase transcript. These results demonstrate that rearrangement of heavy chain immunoglobulin genes normally occurs prior to that of light chain genes and further indicate that the transcriptional competence of the kappa constant region locus is established prior to the time of its rearrangement.

Animals↗
PubMed1981

Cost effective lab service system: better quality medicine at lowered costs.

In this article, the authors describe the Cost Effective Laboratory Service System, a new concept which they explain can reduce hospitalization costs while maintaining or enhancing the quality of medical care. Discussed are the operational features of the system, the development of subsets, prototype trials, and the advantages of and objections to the system.

Cost-Benefit Analysis↗