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J Ritz

Publications and source records attributed to J Ritz.

At least 163 records · Page 9Linked to original sources
PubMed1988

Molecular cloning of the common acute lymphoblastic leukemia antigen (CALLA) identifies a type II integral membrane protein.

Common acute lymphoblastic leukemia antigen (CALLA) is a 100-kDa cell-surface glycoprotein expressed on most acute lymphoblastic leukemias and certain other immature lymphoid malignancies and on normal lymphoid progenitors. The latter are either uncommitted to B- or T-cell lineage or committed to only the earliest stages of B- or T-lymphocyte maturation. To elucidate to homogeneity, obtained the NH2-terminal sequence from both the intact protein and derived tryptic and V8 protease peptides and isolated CALLA cDNAs from a Nalm-6 cell line lambda gt10 library using redundant oligonucleotide probes. The CALLA cDNA sequence predicts a 750-amino acid integral membrane protein with a single 24-amino acid hydrophobic segment that could function as both a transmembrane region and a signal peptide. The COOH-terminal 700 amino acids, including six potential N-linked glycosylation sites compose the extracellular protein segment, whereas the 25 NH2-terminal amino acids remaining after cleavage of the initiation methionine form the cytoplasmic tail. CALLA+ cells contain CALLA transcripts of 2.7 to 5.7 kilobases with the major 5.7- and 3.7-kilobase mRNAs being preferentially expressed in specific cell types.

Amino Acid Sequence↗
PubMed1988

Identification of a second transforming gene, rasn, in a human multiple myeloma line with a rearranged c-myc allele.

Multiple myeloma is a disease characterized by a long, slowly progressive phase and a final, more aggressive one. Little is known about the mechanism of transformation of myeloma cells, although the clinical characteristics of the disease suggest a multi-step process. Recently, a myeloma cell line, NCI-H929, was isolated from a patient with aggressive preterminal disease and found to have a rearranged myc allele. This myeloma cell line has been further characterized in a focus formation assay to determine whether its unusual growth characteristics were associated with a second activated transforming gene. We now report that the NCI-H929 myeloma cell line has an activated rasn allele in addition to a rearranged myc allele. This is the first identification of an activated transforming gene in a multiple myeloma cell line; furthermore, the characterization of two independently activated oncogenes in this B cell malignancy has implications for both the pathogenesis and evolution of the disease.

Animals↗
PubMed1987

Phenotypic and functional deficiency of natural killer cells in patients with chronic fatigue syndrome.

Natural killer (NK)3 cells are large granular lymphocytes that appear to play a significant role in the host's defense against viral infection. We performed an extensive phenotypic and functional characterization of NK cells on 41 patients with the chronic fatigue syndrome (CFS), or "chronic active Epstein-Barr virus infection" syndrome, and on 23 age- and sex-matched asymptomatic control subjects in an attempt to further characterize this illness. These studies demonstrated that a majority of patients with CFS have low numbers of NKH1+T3- lymphocytes, a population that represents the great majority of NK cells in normal individuals. CFS patients had normal numbers of NKH1+T3+ lymphocytes, a population that represents a relatively small fraction of NK cells in normal individuals. When tested for cytotoxicity against a variety of different target cells, patients with CFS consistently demonstrated low levels of killing. After activation of cytolytic activity with recombinant interleukin 2, patients were able to display increased killing against K562 but most patients remained unable to lyse Epstein-Barr virus-infected B cell targets. Additional cytotoxicity experiments were carried out utilizing anti-T3 monoclonal antibody to block killing by NKH1+T3+ cells. These experiments indicated that the NK cell that appears to be responsible for much of the functional activity remaining in patients with CFS belongs to the NKH1+T3+ subset, which under normal circumstances represents only approximately 20% of the NK cell population.

Antibodies, Viral↗
PubMed1987

Lymphoma with clonal T-cell receptor gene rearrangement in a 25-year survivor of Hodgkin's disease.

A woman was treated for Hodgkin's disease, remained disease-free for 25 years, and then developed waxing and waning adenopathy during the next 2 years. The histologic examination of a lymph node biopsy specimen showed a T-cell non-Hodgkin's lymphoma. The patient's indolent clinical course prompted a second biopsy to obtain tissue for T-cell receptor gene rearrangement studies. A southern blot analysis using a human T-cell receptor beta chain probe showed a new band of rearranged DNA, which confirmed the diagnosis of T-cell lymphoma.

Adult↗
PubMed1987

Prolonged disease-free survival after autologous bone marrow transplantation in patients with non-Hodgkin's lymphoma with a poor prognosis.

Despite advances in the primary treatment of non-Hodgkin's lymphoma, relapse is common and treatment after relapse is unsatisfactory. Autologous bone marrow transplantation, although sometimes successful, has generally had disappointing results. We conducted a trial of such transplantation in patients with relapsed non-Hodgkin's lymphoma, using strict criteria in selecting patients; we included only those in whom disease was minimal after conventional treatment (nodal disease less than 2 cm and bone marrow involvement less than or equal to 5 percent on histologic examination) and whose tumor cells expressed the B1 antigen. Forty-nine patients meeting these criteria received cyclophosphamide and whole-body irradiation supported by transplantation of autologous bone marrow that had been treated in vitro with anti-B1 monoclonal antibody and complement. All patients had features of a poor prognosis, including relapse from primary chemotherapy, histologic conversion to more aggressive disease, and extra-nodal dissemination. Thirty-three patients had a history of bone marrow involvement--16 at the time that marrow was obtained. Hematologic and immunologic engraftment was achieved in all patients. Only two treatment-related deaths occurred, from venoocclusive disease of the liver and intracerebral hemorrhage, respectively. Disease-free remission without maintenance therapy has lasted from greater than 2 to greater than 52 months in 34 patients (median follow-up, greater than 11 months). These results are similar to those obtained in patients with advanced, high-grade non-Hodgkin's lymphoma treated with primary combination chemotherapy. This study demonstrates that autologous bone marrow transplantation has tolerable toxicity and high efficacy in a subset of patients who are otherwise incurable but still responsive to cytoreductive therapy. The results suggest a role for such transplantation in the treatment of selected patients with newly diagnosed non-Hodgkin's lymphoma.

B-Lymphocytes↗
PubMed1987

Identification and cloning of a prethymic precursor T lymphocyte from a population of common acute lymphoblastic leukemia antigen (CALLA)-positive fetal bone marrow cells.

We have cloned common acute lymphoblastic leukemia (CALLA)-positive cells from human fetal bone marrow containing less than 1 in 10,000 E-RFC in round-bottomed microtiter wells (one cell per well) using the autocloning unit of an EPICS-V cell sorter. Expansion of such cells (with IL-2 and heavily irradiated autologous thymocytes as feeder cells) resulted in growth in 6-14% of the wells (mean, 11%) with cells with mature T lymphocyte phenotype. Two-color fluorescence analysis of outgrowing cultures furthermore ascertained that these cells had differentiated through a phase of simultaneous expression of T4 and T8 antigens and at the same time expression of the thymocyte-associated T6 antigens. Thus, given the fact that 10-20% of T cell acute lymphoblastic leukemia (T-ALLs) are CALLA+, we have been able to identify a human prethymic T lymphocyte population that might be the normal counterpart of precursor cell to the CALLA+ T-ALL cell.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1987

Enhancement of natural killer function through activation of the T11 E rosette receptor.

Natural killer (NK) cells, which represent a small fraction of normal peripheral blood mononuclear cells, were purified by immunofluorescent cell sorting of NKH1+ cells. cytotoxicity of NKH1+ cells could be enhanced through activation by monoclonal antibodies (anti-T11(2) and anti-T11(3)) specific for epitopes of the sheep erythrocyte receptor or by recombinant interleukin-2 (rIL-2). After 18 h, incubation with both anti-T11(2/3) and rIL-2 resulted in similar levels of enhanced cytotoxicity against NK-resistant as well as NK-sensitive targets. Before and after induction, cytotoxicity was found predominantly within the NKH1+ population. These results suggest that several distinct mechanisms may be capable of enhancing NK activity and that the cells responsible for lymphokine-activated killing are likely to be the same population capable of spontaneous or natural killing before activation in vitro.

Antibodies, Monoclonal↗
PubMed1987

Epstein-Barr virus-transformed B-cell line (DV-1) derived from bone marrow of a patient with severe combined immunodeficiency and immunoblastic lymphoma.

An Epstein-Barr virus-transformed B-cell line derived from a patient with severe combined immunodeficiency who died of a lymphoreticular malignancy has been characterized. The line derived from bone marrow cultures and designated DV-1 shows surface and cytoplasmic IgM and staining with fluorescent monoclonal antibodies against immunoglobulin heavy and light chains mu, delta, and kappa, Dr, and several other B-cell surface antigens. DV-1 secretes IgM kappa and demonstrates monoclonality on analysis of immunoglobulin heavy and light chain gene rearrangement patterns. Incubation with either phytohemagglutinin or pokeweed mitogen failed to cause significant stimulation of proliferation of DV-1 and another EBV-transformed B-cell line derived from an immunologically normal host (LA-350), whereas incubation with Staphylococcus aureus Cowan strain 1 led to significant inhibition of DV-1 and LA-350. Rabbit IgG antibody specific for human immunoglobulin mu-chains produced a dose dependent stimulation of both lines. The responses of DV-1 and LA-350 to mitogens and anti-mu were not as high as those of normal peripheral blood lymphocytes. This spontaneously derived Epstein-Barr virus-transformed B-cell line from a patient with severe combined immunodeficiency demonstrated functional characteristics similar to a B-cell line derived from an immune competent host. While these cells spontaneously incorporate 200 times more thymidine than normal resting peripheral blood lymphocytes, they retain their ability to be modulated by antiimmunoglobulin, and staphylococcal Cowan strain 1, but are unresponsive to the effects of B-cell growth factor.

B-Lymphocytes↗
PubMed1987

In vitro regulation of human hematopoiesis by natural killer cells: analysis at a clonal level.

We studied the effects of a series of well-characterized clones of human natural killer (NK) cells on the proliferation of highly purified normal marrow hematopoietic progenitor cells. Individual NK clones suppressed granulocyte, monocyte, erythroid, or mixed colony formation in a heterogeneous but clonally stable manner. Inhibition of colony growth required a period of close cell contact between NK cell and progenitor cell with maximum inhibition occurring after 8 to 18 hours of preincubation time. The mechanism of killing was at least partially humoral, however, as cell-free supernatants generated by NK clones "activated" by contact with a target cell also inhibited progenitor cell growth. One of the possible humoral mediators was identified as gamma-interferon by studies with specific neutralizing monoclonal antibodies. These results show that clonal NK lines can be further activated by coming in contact with hematopoietic progenitor cells, resulting in substantial inhibition of colony formation in vitro.

Antigens, Surface↗
PubMed1987

Ultrastructural evidence that the granules of human natural killer cell clones store membrane in a nonbilayer phase.

Electron-microscopic examination of five LGL clones, JT3, JTB18, CNK6, CNK7, and CNK10, expressing natural killer activity and T11 and NKH1 phenotype, showed that three of the clones, JT3, CNK6, and CNK7, had crystalline structures in their densest granules. These structures generally consisted of hexagonally packed lattices with a 6.9-nm point-to-point spacing. JTB18 and CNK10 had no structures in their granules. The attack of one clone, JT3, on two resistant target tumor cell lines, KG1 and Laz509, was also examined under three conditions. First, JT3 cells and targets were incubated together. There was little adherence, degranulation, or killing. Second, cells were incubated with anti-T11(2) and T11(3), antibodies against the E-rosette receptor/antigen complex, which activate resting T cells and enhance cytolytic activity of NK clones and CTL. JT3 cells adhered to the targets, formed zones of apposition between NK and target cell membranes, polarized, and degranulated into the space between the two cells, killing the targets. Third, cells were incubated with both anti-T11(2/3) and anti-LFA-1, an antibody that inhibits adherence. The JT3 cells did not form zones of apposition with the targets, but degranulated in discrete areas on their own surface. In all cases, discharged crystalline granules transformed to sheets of membrane and vesicles. These studies suggest that phospholipids are packed in hexagonal lattices in the granules of the resting cells and transform to bilayer structures during exocytosis. The crystalline nature of the granule may immobilize lytic molecules and protect the resting cell from lysis. Further, the vesicles may serve to transport the lytic molecules from the effector to the target cell. Anti-LFA-1 does not inhibit target recognition or exocytosis, but instead blocks membrane interactions of the effector cell with its target.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1987

Hematologic engraftment and immune reconstitution posttransplantation with anti-B1 purged autologous bone marrow.

Hematologic engraftment and immune reconstitution were examined in patients who received cyclophosphamide and total body irradiation therapy followed by infusion of autologous bone marrow purged with anti-B1 monoclonal antibody (MoAb) and complement as therapy for non-Hodgkin's lymphoma. Hematologic engraftment was prompt with return of greater than or equal to 0.5 X 10(3)/microL granulocytes and greater than or equal to 2 X 10(4)/microL platelets at a median of 26 and 29 days posttransplant, respectively. Immunologic reconstitution, in contrast, was prolonged. Normal numbers of circulating B cells were consistently noted by five months posttransplant, whereas return of normal immunoglobulin levels in some patients did not occur for one year. Normal numbers of T cells were evident within the first month posttransplant, but a reversed T4:T8 ratio persisted in some patients up to three years. In vitro responses of either B cells to triggers of activation or of T cells to mitogens and antigens were not normal for at least three months posttransplant. Natural killer (NK) cells predominated early after transplant and may demonstrate cytotoxicity against tumor cells. Our studies demonstrate that transplantation with anti-B1 purged autologous bone marrow results in complete hematologic and delayed immunologic engraftment. No significant acute or chronic clinical toxicities have been observed.

Antibodies, Monoclonal↗
PubMed1986

A subset of natural killer cells in peripheral blood displays a mature T cell phenotype.

Normal human PBMC were analyzed for the presence of cells expressing both T3 and NKH1 antigens, using direct two-color immunofluorescence. In six individuals, NKH1+T3+ cells were found to represent 2.5% of PBMC and 24% of the total number of NKH1+ cells. Purified NKH1+T3+ cells were shown to have the typical morphology of large granular lymphocytes (LGL). NKH1+T3+ cells also exhibited spontaneous cytotoxicity against K562 target cells and this lytic activity could be inhibited by anti-T3 mAb. Similar results were obtained with NKH1+T3+ cells cultured in vitro in lymphocyte-conditioned medium. Taken together, these results indicate that NKH1+T3+ cells represent a unique population of NK-active cells in normal peripheral blood. Although these cells exhibit LGL morphology and NK activity, this appears to be mediated through a functional T cell-like receptor for target antigen.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1986

A lymphokine that activates the cytolytic program of both cytotoxic T lymphocyte and natural killer clones.

A 10-12 kD lymphokine, herein termed TCAF, was recently shown to be secreted from Th after crosslinking of their antigen/MHC (T3-Ti) receptors. TCAF stimulates resting T lymphocyte proliferation via binding to surface components of the T11 pathway. To determine whether TCAF could induce antigen-independent activation of the lytic machinery of cytotoxic cells, the present studies were conducted. In the presence of TCAF, both T8+ class I MHC-specific and T4+ class II MHC-specific cytotoxic T cell clones were induced to kill targets, including those lacking the appropriate MHC molecules. This effect was unique to TCAF, since IL-1, IL-2, IFN-gamma could not stimulate lytic activity. Furthermore, both T3+T11+ and T3-T11+ NK clones were triggered to lyse NK-resistant target cells. These findings suggest that TCAF can function in an antigen-independent fashion to amplify cytotoxic effector responses.

Antibodies, Monoclonal↗
PubMed1986

Expression of the NKTa clonotype in a series of human natural killer clones with identical cytotoxic specificity.

Over a period of 3 yr, a series of ten NK clones that express a unique clonotypic T cell receptor-like structure, termed NKTa, has been generated from a single individual. These clones were derived from either peripheral blood nonadherent cell fractions (JT9, JT10, JT11), NKH2-purified cells (CNK8, CNK9), or NKTa-purified cells (CNK11, CNK12, CNK13, CNK14, CNK15). Flow cytometric analysis of peripheral blood mononuclear cells from this individual showed that NKTa+ cells occur with a frequency of approximately 0.15%. The existence of NKTa+ cells in peripheral blood was confirmed by use of immunorosette enrichment techniques, flow cytometric purification, and subsequent clonal expansion of NKTa+ cells. Phenotypic analysis of NKTa+ clones showed that all expressed NKH1 as well as T3, T8, T11, T12, and Mo1 antigens. Only five of ten clones expressed NKH2 antigen. All NKTa+ clones had broad cytolytic activity against a series of seven different target cells that was similar to that of other NK clones. In addition, cytotoxicity of each clone could be inhibited by preincubation of effector cells with monoclonal anti-NKTa or by preincubation of target cells with monoclonal anti-TNKTAR. Although half of the NKTa+ clones appeared phenotypically different from the other half with regard to the expression of NKH2 antigen, analysis of T cell receptor gene rearrangements indicated that all NKTa+ clones contained identical gene rearrangements of C beta 2.

Antibodies, Anti-Idiotypic↗
PubMed1986

Function of the LFA-1 and T4 molecules in the direct activation of resting human B lymphocytes by T lymphocytes.

Activated T lymphocytes can provide all of the signals necessary to induce the proliferation of resting B lymphocytes. The activation signal is presumably initiated through direct T-B lymphocyte contact. The role of the leukocyte function antigen-1 (LFA-1) and T4 molecules in the activation of purified, small B lymphocytes by mitomycin C-treated T lymphocytes was examined by using monoclonal antibodies that react with and inhibit the function of these molecules. Anti-LFA-1 antibody binding significantly inhibited T-B lymphocyte interactions that result in B lymphocyte proliferation. In contrast, the presence of anti-T4 antibodies at concentrations as high as 100 micrograms/ml did not inhibit this interaction. These results indicate that the B lymphocyte activation signal may not be mediated through the interaction of T4 molecules with major histocompatibility complex class II antigens of the B lymphocyte but is a cell-cell contact-dependent event that is facilitated by LFA-1 molecules.

Antibodies, Monoclonal↗