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D H Ryan

Publications and source records attributed to D H Ryan.

At least 91 records · Page 5Linked to original sources
PubMed1990

Rearrangement of the T-cell receptor alpha, beta and gamma chain genes in chronic lymphocytic leukemia.

Simultaneous expression of mature B-cell and T-cell markers and subsequent abrogation of expression of the T-cell surface markers by cytotoxic chemotherapy was reported earlier in a patient (TG) with chronic lymphocytic leukemia (CLL). In addition to rearrangements of the immunoglobulin (Ig) gene loci correlating with phenotypic data, the T-cell receptor (TCR) alpha, beta and gamma chain genes also displayed clonal rearrangements in peripheral blood lymphocyte DNA of TG. The present case shows that in CLL cells not only the expression of B-cell and T-cell specific differentiation antigens but also the rearrangement of Ig as well as TCR alpha, beta and gamma genes may occur simultaneously.

Aged↗
PubMed1990

Pennington Biomedical Research Center. Philanthropy refocuses nutrition thinking.

Pennington Biomedical Research Center (PBRC) is a $26 million facility constructed as the initial component of a generous gift from Baton Rouge oilman and philanthropist Claude B. "Doc" Pennington. The US Department of Agriculture provided a $9.4 million grant for equipment for the center. The Louisiana Public Facilities Authority provided $4.1 million for initial operating capital, and the center received a $3.5 million grant from the US Army for military nutrition research. The Pennington Center Foundation, a non-profit support organization, has so far raised $4.6 million from individuals, corporations, and private foundations. Traditional academic funding sources such as the National Institute of Health are also providing funding for research.

Financial Management↗
PubMed1989

Characterization of human marrow stromal cells: role in progenitor cell binding and granulopoiesis.

Adherent cell layers and their associated extracellular matrices form when human marrow is incubated in cultures containing hydrocortisone and horse serum. These stromal layers contain cells positive for alkaline phosphatase; secrete collagens types I and III and fibronectin, bind the anti-actin monoclonal antibodies (MoAbs) HHF and CGA-7; stain with oil red O, and express the acetylated LDL receptor. Highly purified CD34 (My10)-positive progenitor cells attach to these stromal layers, and a 16-fold enrichment of CFU-GM in both stromal attachment and semisolid agar assays was observed. Granulopoiesis persisted up to 40 days (mean duration 25 days) after passaged stroma were recharged with stromal cell-depleted target cells in a two-stage liquid marrow culture system. Although equal to marrow fibroblasts in their ability to bind CD34+ myeloid progenitors, stromal layers were better at supporting granulopoiesis. This system provides an in vitro model to characterize the components of stroma and stroma-cytomatrix that enhance marrow progenitor cell localization and maintenance.

Antigens, CD34↗
PubMed1989

Clonal B cell expansions in patients with essential mixed cryoglobulinaemia.

In essential mixed, type II, cryoglobulinaemia (EMC) monoclonal autoantibodies with rheumatoid factor activity are synthesized at an accelerated rate by non-malignant B lymphocytes. In order to determine if the high cryoglobulin production rate is related to a clonal B cell expansion, cell surface markers of peripheral blood lymphocytes (PBL) were analysed by flow cytometry and the rearrangement of immunoglobulin (Ig) genes was investigated by Southern blot analysis of DNA extracted from the PBL of 12 EMC patients. Clonal expansion of B cells could be detected using DNA probes specific for the c kappa, c-mu, and JH genes in four out of 12 patients, two of whom also showed specific expansions of mu heavy and kappa light chain bearing cells using flow cytometry. The rearrangement of the c-myc locus was also noted in one of the patients with detectable Ig gene rearrangements. Demonstration of clonal B cell expansions in EMC patients shows that the clonal type of Ig gene rearrangements are not unique markers of malignant lymphomas but may also occur in autoimmune lymphoproliferative disorders. Since malignant B cell lymphomas can develop in a small number of EMC cases, the follow-up of these patients should be pursued indefinitely.

Adult↗
PubMed1988

Structural polymorphism of the human platelet Fc gamma receptor.

A variable T lymphocyte proliferative response to murine IgG1 anti-T3 monoclonal antibodies, in which most North American Caucasians respond whereas a minority do not, is well established. This is most likely the result of a genetic polymorphism manifested by 1) the inability of the monocyte 40-kDa IgG FcR of some individuals to bind murine IgG1, and 2) a distinctive trimorphic pattern on IEF of the monocyte 40-kDa FcR, one form being seen in all individuals who do not respond and another form (or a combination of both forms) being seen in those who do respond. We have evaluated the IEF patterns of the platelet 40-kDa FcR and find that in every individual tested the pattern for platelet FcR correlates with that seen for the monocyte 40-kDa FcR pattern. Furthermore, the platelets of those individuals whose "nonresponder" monocyte 40-kDa FcR did not mediate a murine IgG1 anti-T3 response did not respond with an aggregation reaction to murine IgG1 immune complexes (opsonized E). In contrast, platelets from donors possessing "responder" monocytes displayed positive "aggregation" responses to E coated with murine IgG1 antibody. However, the platelet FcR structural polymorphism described earlier did not correlate with the donor-specific variability in capacity of platelets to respond functionally to aggregated human IgG described in an earlier paper. Rather, the variation in capacity of platelets from individual donors to respond functionally to aggregated human IgG was related to the quantitative expression of platelet FcR. These data indicate that the molecular mechanisms responsible for the platelet 40-kDa FcR structural polymorphism are quite different from the mechanisms governing the variation in quantitative expression of the receptor.

Animals↗
PubMed1988

Expression of IgG Fc receptors in myeloid leukemic cell lines. Effect of colony-stimulating factors and cytokines.

Three classes of FcR have been defined on human myeloid cells by their reactivity with mAb; FcRI (mAb 32); FcRII (mAb IV3); and FcRIII (mAb 3G8). We have quantitated the expression of each FcR on human myeloid leukemia cells and cell lines (KG-1, HL-60, U937, and K562). Detailed analysis of FcR surface expression is provided for the U937 cell line after exposure to CSF and cytokines. Increased expression of FcRI and FcRII occurred at 72 h in cells exposed to GCT or Mo cell line-conditioned medium as well as to medium from PHA-treated mononuclear cells. The augmentation of FcRII required protein synthesis and was diminished by a neutralizing antibody to granulocyte-macrophage CSF. We also show that fractions containing natural granulocyte CSF or granulocyte-macrophage CSF as well as r-granulocyte and r-granulocyte-macrophage CSF are capable of inducing FcRII on these cells, whereas other cytokines such as IL-1 and IL-2, TNF-alpha, INF-gamma and macrophages CSF failed to do so.

Antibodies, Monoclonal↗
PubMed1988

Hu-ets-1 gene in congenital leukemia with t(11;19)(q23;p13).

Cytogenetic analysis of the leukemic cells from a 1-day-old baby with an acute myelomonocytic leukemia revealed them to contain a chromosome change of t(11;19)(q23;p13). Molecular studies using a 980 bp HindIII/HpaI digested v-ets probe showed no DNA rearrangements, deletions, or amplification in the leukemic cells, including the JH immunoglobulin and T-cell receptor (alpha or beta) genes. The findings indicate that the leukemic cells with t(11;19)(q23;p13) appear not to contain a transposition or rearrangement of the protooncogene Hu-ets-1 located at 11q23, as previously described in leukemic cells with t(4;11)(q21;q23) and t(9;11)(p22;q23). The leukemic cases with t(11;19)(q23;p13) studied by us showed a phenotype compatible with their myelomonocytic nature, although it is possible that other cases may have a lymphoid phenotype.

Chromosomes, Human, Pair 11↗
PubMed1987

Human Fc gamma receptors: stable inter-donor variation in quantitative expression on platelets correlates with functional responses.

Evidence has recently been presented that a 40,000 dalton membrane sialoglycoprotein (p40) shared by monocytes and granulocytes serves as the human platelet receptor for aggregated IgG. We now report that the platelets of normal donors exhibit stable quantitative differences in the expression of this receptor molecule, as determined by flow cytometry using fluorescent staining with murine monoclonal antibody to p40 (mab IV.3). These inter-donor differences were reproducible on repeated testing over at least 4 mo. In concurrent assays, the binding of mab IV.3 to each donor's platelets was highly correlated with the binding of heat-aggregated human IgG, also assayed by flow cytometry. The biological relevance of this quantitative variation in IV.3 binding is suggested by its reproducible correlation with platelet responsiveness to aggregated IgG measured by aggregometry. Such stable quantitative variation in platelet Fc receptor expression among individual humans could contribute to differences in severity of certain pathologic processes initiated by IgG-containing immune complexes.

Antibodies, Monoclonal↗
PubMed1987

Structural polymorphism of the human monocyte 40 kilodalton Fc receptor for IgG.

The 40 kD monocyte Fc receptor for IgG is capable of binding murine IgG1 and of supporting an IgG1 anti-T3 T lymphocyte proliferative response among approximately 80% of Caucasian individuals (responders), whereas the 40 kD Fc receptor on monocytes of the remaining individuals (nonresponders) is incapable of interacting with murine IgG1. By using a monoclonal antibody (mab IV3) that reacts with the 40 kD receptor, we found that the monocyte 40 kD receptors from responder and nonresponder individuals cannot be distinguished by either electrophoretic mobility on SDS-polyacrylamide gels, or by the number of receptors per cell as determined by indirect immunofluorescence. However, isoelectric focussing of the purified radioiodinated 40 kD receptor revealed that the monocyte receptor from all of four nonresponder individuals evaluated has a single distinctive pattern of multiple, regularly spaced bands, whereas the pattern of the 40 kD monocyte receptor from 11 responder individuals is of two sorts. One (seen in four of 11 responders) consists of multiple, regularly spaced bands that are asynchronous with the nonresponder pattern, and the other (seen in seven of 11 responders) consists of multiple bands that correspond in mobility to all of the bands of both of the other two patterns. The incidence of these three patterns suggests that the 40 kD Fc receptor is encoded by a single structural gene with two alleles, both of which are expressed.

Antibodies, Monoclonal↗
PubMed1987

Translocation between chromosomes 7 and 11 in nonlymphocytic neoplasia.

Three cases with chromosome changes involving bands 7p14 or 7p15 and 11p15 are described: one was a Japanese female with an acute myelomonocytic leukemia, the second was a white female with a 10-year history of paroxysmal nocturnal hemoglobinuria who developed a myelodysplastic syndrome, and the third was a patient with Ph-negative atypical chronic myelogenous leukemia with trisomy 8 and a chromosome change involving bands 7p14 and 11p15. These cases possibly indicate that the t(7;11)(p14 or p15;p15) change may characterize a subset of human nonlymphocytic neoplasia.

Adult↗
PubMed1987

Development of class I-specific helper-inducer T-cell clone.

A unique alloreactive human helper-inducer T-cell clone which reacts with the class I HLA antigen was characterized. The clone was derived from a mixed lymphocyte culture between cells from a HLA-A2-; B35,w51; Bw4,Bw6; Cw4,-; DR1,4; DQw1,-; DRw53 responder and a HLA-A2,3; B7,14; Bw6; Cw8,-; DR7,-; DQw2,w3; DRw52 stimulator. When screened against a panel of stimulator cells, this clone was found to have a specificity towards a stimulator HLA-B14 and consisted entirely of Leu-4, Leu-3, and 4B4 positive T cells, which is a T helper-inducer phenotype. Using monoclonal antibodies directed towards various monomorphic class I and II HLA epitopes in an inhibition experiment, it was found that both monoclonal antibodies w6/32 and 4E (recognizing class I monomorphic and HLA-B epitopes, respectively) inhibited proliferation. However, monoclonal antibodies BBm.1 and L227 (directed against beta 2-microglobulin and Ia-like molecule, respectively) had no inhibitory effect. Functional evaluation of this clone demonstrated helper activity on the proliferation of MLC response. The helper-induction effect on MLC cultures remained intact following irradiation of the clone for either 500 or 2000 rad suggesting that helper function of the clone was radiation resistant. The helper activity of this clone was MHC nonrestricted since it enhanced proliferation of the original responder and stimulator MLC as well as third and fourth party individuals. By CTLL cell line proliferation assay, this clone was found to release IL-2. When assayed (day 1 to 7) for class II HLA products expression following stimulation, HLA-DRw53 was consistently expressed by the clone. However, HLA-DR1, DQw1 were found to be expressed simultaneously on day 2 through day 7 and HLA-DR4, DQw3 on day 2 and 3. These data demonstrate, for the first time, the generation of a class I specific helper-inducer T-cell clone in MLC response.

Antibodies, Monoclonal↗
PubMed1987

Phenotypic similarities and differences between CALLA-positive acute lymphoblastic leukemia cells and normal marrow CALLA-positive B cell precursors.

Expression of differentiation markers in common acute lymphoblastic leukemia (cALL) cells from 25 patients was compared with subpopulations of normal common ALL antigen (CALLA) (CD10)-positive bone marrow lymphoid cells (cBMLs). In cBML, CD10 intensity is positively correlated with CD34 (MY10) and terminal transferase (TdT) expression and inversely correlated with common leukocyte antigen (CLA), CD20 (B1), and ctyoplasmic mu chain (Cmu) expression. In cALL, CD10 density was inversely correlated with CLA and Cmu expression and strongly correlated with CD34 expression as in cBML. In contrast to cBML, TdT and CD20 expression were not related to CD10 density in cALL. Furthermore, cALL TdT intensity measured by enzyme immunoassay was not related to expression of CD10, CLA, or CD34, but was positively correlated with CD20 expression. Cmu expression in cALL was inversely correlated with expression of CD34 and positively correlated with CLA as in cBML, but showed no association with TdT intensity or CD20 expression in contrast to the relationship found in cBMLs. Analysis of TdT intensity and Cmu expression in sorted subpopulations of cells from individual patients that were positive or negative for CD34, CD20, or CD10 was consistent with the data obtained by comparison of cells from different patients. These results indicate that from patient to patient and within individual patients, cALL cells express the markers CD34, CLA, CD10, and Cmu in a coordinated fashion similar to cBMLs, but demonstrate differences in expression of TdT and CD20 with respect to the marrow cells considered their normal counterparts. The cALL cells that are CD34 positive show increased expression of CD10 and are less likely to be CLA or Cmu positive, suggesting that they may represent a phenotypically less differentiated form of cALL than does CD34-negative cALL.

Acute Disease↗
PubMed1986

Monoclonal antibodies to Fc receptors for IgG on human mononuclear phagocytes. Antibody characterization and induction of superoxide production in a monocyte cell line.

We have utilized monoclonal antibodies against the two IgG Fc receptors (p40 and p72) of U937 cells to stimulate the release of superoxide. The monoclonal antibody (mAb) specific for p40 (IV3) has been described elsewhere. A murine IgG1 mAb specific for the high affinity p72 Fc receptor (designated mAb FcR32 or simply mAb 32) bound to the same p72 precipitated by Sepharose-human IgG as shown by preclearing experiments and by identical isoelectric focussing patterns. Binding of mAb 32 to p72 was independent of the Fc region of the antibody since Fab' fragments of mAb 32 affinity adsorbed p72. The binding of both mAb 32 and human IgG1 to the intact U937 cell was not reciprocally inhibitory, indicating that mAb 32 does not interfere with the ligand binding site of p72. mAb 32 bound to human monocytes, U937, and HL60 cells, but not to granulocytes or lymphocytes. U937 cells cultured in gamma-interferon and 1,25-dihydroxycholecalciferol generated superoxide when incubated with mAb 32 or IV3 followed by cross-linking with F(ab')2 anti-murine Ig. Incubation with mAb 32 or IV3 alone or with 3 of 5 other anti-U937 mAbs cross-linked with anti-murine Ig did not result in superoxide generation. Immune complex-mediated superoxide production was inhibited 80% by IgG, but not by mAb 32 or IV3.

Antibodies, Monoclonal↗