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Biomedical subjects

L G Lum

Publications and source records attributed to L G Lum.

At least 73 records · Page 4Linked to original sources
PubMed1985

Leukemia of large granular lymphocytes: association with clonal chromosomal abnormalities and autoimmune neutropenia, thrombocytopenia, and hemolytic anemia.

Three patients had leukocytosis of large granular lymphocytes and chronic neutropenia. Clonal chromosomal abnormalities (trisomy 8 and trisomy 14) and lymphocytic infiltration of splenic red pulp, hepatic sinusoids, and bone marrow indicated the neoplastic nature of the large granular lymphocytes. Demonstration of a T3+, T8+, HNK-1 + phenotype and low natural killer cell activity that was augmented by interferon treatment showed the leukemic cells to be immature natural killer cells. Multiple autoantibodies were present and included rheumatoid factor and antinuclear, antineutrophil, antiplatelet, and antierythrocyte antibodies, suggesting a defect of B-cell immunoregulation. In addition, in-vitro studies showed impaired suppression of immunoglobulin biosynthesis by abnormal cells from one patient. Antineutrophil antibodies and absence of direct cell-mediated inhibition of granulocyte-macrophage colony formation supported a humoral immune mechanism for the neutropenia. In these patients the syndrome of splenomegaly, multiple autoantibodies with neutropenia, and lymphocytosis of large granular lymphocytes is due to a neoplastic proliferation of immature natural killer cells.

Adult↗
PubMed1985

The induction and suppression of in vitro IgG anti-tetanus toxoid antibody synthesis by human lymphocytes stimulated with tetanus toxoid in the absence of in vivo booster immunizations.

This report presents a new approach that by-passes booster immunizations with tetanus toxoid (TT) before in vitro studies of antibody (Ab) production. The methodology for optimal TT-induced synthesis of specific IgG anti-tetanus toxoid Ab (IgG anti-TT) by peripheral blood mononuclear cells (PBMC) from randomly selected TT immune individuals without recent booster immunizations is described. PBMC from most normal immune subjects could be repeatedly induced to produce in vitro IgG anti-TT; PBMC from subjects with high TT titers are not required for this new approach. This approach uses high cell concentrations in multiple replicate microcultures and TT washout to obtain optimal IgG anti-TT synthesis. Washed cultures produced more Ab than nonwashed cultures (p less than or equal to 0.005). The readdition of TT (2.5 to 250 ng/ml) to the culture media after washout of TT on day 4 suppressed specific Ab formation, whereas diphtheria toxoid added at comparable doses did not inhibit specific Ab formation. Suppression of antibody synthesis mediated by T cells could be induced by TT per se, and was not due to binding of synthesized Ab to TT in the latter 8 days of culture. In addition, suppression could not be induced in the first 4 days of culture by IgG anti-TT, IgG, or IgM. This approach permits the analysis of antigen-specific regulatory circuits in the steady and activated immune states, and the evaluation of in vivo and in vitro effects of biologic response modifiers on specific Ab production.

Adult↗
PubMed1985

The regulation of immunoglobulin synthesis after HLA-identical bone marrow transplantation: VI. Differential rates of maturation of distinct functional groups within lymphoid subpopulations in patients after human marrow grafting.

This investigation uses different polyclonal activators of in vitro immunoglobulin production to elicit immunoregulatory profiles of B cells, T cells, T4 cells, and T8 cells from 25 recipients (13 with and 12 without chronic graft-v-host disease [GVHD] ) after HLA-identical marrow transplantation for aplastic anemia or hematologic malignancy. Pokeweed mitogen, Epstein-Barr virus, herpes simplex type 1 virus, and tetanus toxoid were used to induce immunoglobulin production as measured by a plaque assay. Multiple defects in the various lymphoid subsets were found in both groups of patients. There was defective b cell function, lack of T cell or T4 cell subset helper activity, and increased T cell, T4 cell, or T8 cell suppressor activity after stimulation with the various activators. Inconsistent B, T, T4, and T8 cell functions in the marrow graft recipients provide evidence for (a) different functional groups of cells within each subset responsive to different polyclonal activators; (b) a spectrum of immune capabilities within each phenotype lineage; (c) different patterns of immune reconstitution for each lymphocyte subset after marrow grafting; and (d) chronic GVHD altering recovery of in vitro functional responses to the different polyclonal activators.

B-Lymphocytes↗
PubMed1984

In vitro differences in lymphocyte subpopulation reactivity in lung cancer patients: purified protein derivative-specific suppressor T lymphocytes in patients who have received Bacillus Calmette-Guerin.

Antigen-specific responses of lymphocyte to purified protein derivative (PPD) were studied in seven patients with non-small cell lung cancer who had undergone complete resection and received postoperative intrapleural Bacillus Calmette-Guerin. In addition, one patient with unresected lung cancer and reactive tuberculin skin test (PPD +) and five normal PPD- individuals were also studied. Lung cancer patients had significantly fewer responsive peripheral blood lymphocytes, unfractionated T cells, and T cells bearing Fc-IgG receptors (TG + populations) than normal controls. These deficits were most pronounced in the group who had received intrapleural Bacillus Calmette-Guerin but who had failed to develop reactive tuberculin skin tests. In contrast, the TG-populations (FC-IgG receptor-negative T cells) from all patients responded to PPD. TG + cells specifically inhibited TG- -cell responses to PPD in both proliferation and immunoglobulin secretion. Radiosensitive suppressor monocytes were found in other patients. This study shows interesting immune deficits in early lung cancer patients. These patients appear to have PPD-specific suppressor TG + cells which may contribute to the immune deficits in these patients.

Antibody-Producing Cells↗
PubMed1984

Immunologic recovery in human marrow graft recipients given cyclosporine or methotrexate for the prevention of graft-versus-host disease.

Immunologic recovery was studied in ten patients with aplastic anemia and 23 patients with hematologic malignancy who received HLA-identical marrow grafts and cyclosporine postgrafting as prophylaxis against graft-versus-host disease. Cyclosporine , 12.5 mg/kg/day, was administered beginning on the day before marrow infusion and continued for 50 days, when it was tapered and discontinued by 6 months postgrafting . Results were compared with data from concurrent and previously described patients receiving methotrexate as prophylaxis for graft-versus-host disease. Patients treated with cyclosporine or methotrexate had lower-than-normal immunologic parameters and were not different from one another 3-5 months postgrafting . By 11 to 18 months after grafting lymphocyte counts had normalized in both groups. Serum IgA levels were low and IgG levels had normalized in methotrexate-treated patients, and IgM was normal in cyclosporine -treated patients. In vivo antibody production to T-dependent antigens and skin test responses to recall antigens continued to be impaired. The response to the neoantigen dinitrochlorobenzene was still impaired in patients treated with cyclosporine and normal in patients given methotrexate. These data suggest that immunologic recovery after marrow transplantation is similar in cyclosporine -treated and methotrexate-treated patients.

Antibodies, Viral↗
PubMed1984

Immunoglobulin synthesis after HLA-identical marrow grafting. V. The role of peripheral blood monocytes in the regulation of in vitro immunoglobulin secretion stimulated by pokeweed mitogen.

The ability of purified monocytes to regulate in vitro immunoglobulin (Ig) production was examined in 12 patients after HLA-identical marrow grafting. Five patients were studied less than 3 mo after grafting and seven more than 1 yr after grafting. One of the former had acute graft-vs-host disease and five of the latter had chronic graft-vs-host disease. Ficoll-Hypaque-separated peripheral blood mononuclear cells from patients, normal marrow donors, or healthy unrelated individuals were separated into T and non-T cells by sheep erythrocyte rosetting. Highly enriched monocyte and B cell subpopulations were obtained by placing the non-T cells over discontinuous Percoll gradients. Co-cultures of patient or normal monocyte populations with either normal or patient T and B cells with pokeweed mitogen were performed. A hemolytic plaque assay was used to assess Ig secretion after 6 days of culture. Co-culture of T and non-T cells from 10 of 12 patients failed to produce Ig. Monocyte-enriched fractions from all patients provided normal accessory cell functions when co-cultured with normal T and B cells. Two of five patients with chronic graft-vs-host disease had monocytes that suppressed Ig synthesis at high ratios of monocytes to normal T and B cells. Normal monocyte-enriched fractions did not restore Ig production to T and B cells of patients whose T and non-T cells failed to produce Ig. These data indicate that the observed defects in pokeweed mitogen-driven Ig secretion after marrow grafting are due primarily to defective T and B cell functions and that the monocyte accessory function is intact in most patients studied.

Adolescent↗
PubMed1983

The proportion of TA, TG, and TM cells in various immunodeficiency and autoimmune disorders.

Patients with various immunodeficiency and autoimmune disorders were examined for the proportions of T cells bearing Fc-IgA, Fc-IgG, and Fc-IgM receptors. These disorders included common variable immunodeficiency, systemic lupus erythematosus, ataxia-telangiectasia, selective IgA deficiency, and the Wiskott-Aldrich syndrome. Abnormal proportions (higher or lower than an interval containing 95% of our normal values) of Fc-IgA receptor-bearing T cells (TA) were found in common variable immunodeficiency, systemic lupus erythematous, ataxia-telangiectasia, and selective IgA deficiency. However, the proportion of T cells bearing Fc receptors did not correlate with their functional activity in in vitro immunoglobulin production assays.

Ataxia Telangiectasia↗
PubMed1983

The regulatory roles of T4 and T8 subsets in tetanus toxoid-induced in vitro immunoglobulin production.

A new mitogenic system for in vitro immunoglobulin production induced by tetanus toxoid is presented and the role of T4 and T8 subsets in tetanus toxoid-induced in vitro immunoglobulin production is investigated. Purified T, T4, T8, and B cells from normal individuals previously immunized but not boosted with tetanus toxoid were cultured in helper and suppressor assays and the number of immunoglobulin-secreting cells were enumerated after culture using a hemolytic plaque assay. The regulatory roles of T4 and T8 cells in this tetanus toxoid system were compared with the role of these subsets after pokeweed mitogen stimulation. Although most of the immunoglobulin produced in the tetanus toxoid system was polyclonal, there were differences in the time course, the magnitude of the responses, the radiosensitivity of the subsets, and optimal T- to B-cell ratios for immunoglobulin production which distinguish the tetanus toxoid and pokeweed mitogen systems.

Antibodies, Bacterial↗
PubMed1983

Human monocyte-histiocyte differentiation antigens identified by monoclonal antibodies.

Two distinct differentiation antigens of human myelomonocytic cells are defined using murine monoclonal antibodies. The antigens recognized by antibodies 20.2 and 20.3 are expressed by all cells of the monocyte lineage in both peripheral blood and bone marrow. Cell-sorting experiments demonstrated that histiocytes and immature bone marrow cells with detectable alpha-naphthyl butyrate esterase activity also express both antigens. Within cells of other lineages, the antigens had distinct patterns of expression. Immature myeloid cells were 20.2 negative, but 20.3 positive; whereas mature myeloid cells were 20.2 positive, but 20.3 negative. Nucleated erythroid cells and platelets expressed only the 20.3 antigen. These results indicate that myeloid and monocytic cells share common differentiation antigens with cells of the erythroid and megakaryocytic lineages. The 20.2 and 20.3 antibodies reacted with the leukemic cells from some patients with acute nonlymphocytic leukemia (FAB, M1-M5) and with some cell lines derived from patients with nonlymphocytic leukemia, but not with blast cells from patients with lymphoid leukemia or with lymphoid leukemic cell lines. These antibodies may prove useful in studying the differentiation of bone marrow stem cells, in defining the cellular origins and classification of leukemias, and in the identification of distinct prognostic subgroups of acute nonlymphocytic leukemia.

Antibodies, Monoclonal↗
PubMed1983

Chronic lymphocytosis with neutropenia: evidence for a novel, abnormal T-cell population associated with antibody-mediated neutrophil destruction.

A 67-year-old man with stable chronic neutropenia, lymphocytosis, multiple auto-antibodies, and recurring infections was studied in order to characterize the abnormal lymphocytes and the mechanism of neutropenia. One-half of the circulating mononuclear leukocytes were large granular lymphocytes that did not rosette with sheep erythrocytes and did not have surface immunoglobulin or receptors for C3 or IgG Fc. Virtually all of the mononuclear leukocytes, however, reacted with three monoclonal antibodies specific for mature T lymphocytes--OKT3, 3A1, and 12.1--the latter with a bimodal pattern on FACS analysis. The nonadherent, non-E-rosetting lymphocytes consisted of a homogeneous population of T cells with a novel phenotype: 3A1+, OKT3+, OKT8+, Ia+, 12.1+, OKT4-, 9.6-, 10.2-, Fc gamma receptor-. The abnormal phenotype of these cells suggested that they may have developed clonally. In spite of their OKT8+ phenotype, these lymphocytes were functionally abnormal, since they did not suppress B-cell immunoglobulin production in vitro. A humoral immune mechanism of neutropenia was indicated by increased levels of neutrophil-reactive IgG and in vivo kinetic studies with autologous neutrophils demonstrating shortened intravascular survival. The granulocyte turnover was normal, however, suggesting a blunted marrow response to the neutropenia. Corroborating the kinetic data, in vitro cultures of the patient's blood and marrow cells showed reduced numbers of granulocytic progenitors (CFU-C). Neither blood lymphocytes nor serum from the patient suppressed growth of allogeneic CFU-C nor did removal of OKT8+ cells from the marrow increase CFU-C expression. Thus, the disorder in this patient is characterized by proliferation of abnormal OKT8+ lymphocytes with impaired suppressor function. Our findings suggest that the neutropenia was due to anti-neutrophil autoantibodies that may have resulted from abnormal T-cell immunoregulation.

Aged↗
PubMed1983

Recombinant leukocyte A interferon for the treatment of serious viral infections after marrow transplant: a phase I study.

Six marrow-transplant patients with serious virus infections (four with cytomegalovirus and two with adenovirus) were treated with recombinant leukocyte alpha interferon at daily doses of 6,000,000-50,000,000 units to determine safety and tolerance. Fever and gastrointestinal side effects attributable to interferon occurred in two patients each. Hepatic function abnormalities were observed in all six patients, although five had such abnormalities before treatment. Treatment of one patient was stopped because of apparent suppression of marrow activity. Natural cytotoxic activity increased in the four patients treated for cytomegalovirus infection. All six patients died of pneumonia, with four proven to have cytomegalovirus-related pneumonia at autopsy. Except for the presence of abnormal hepatic function, recombinant leukocyte alpha interferon was well tolerated after marrow transplantation. Efficacy remains to be established in treatment or prophylactic trials.

Adenoviridae Infections↗
PubMed1983

Functional diversity in OKT4 and OKT8 subsets from long-term survivors after HLA-identical marrow grafting.

T and B cells from one short-term and nine long-term patients who had received HLA-identical bone marrow transplants for aplastic anemia or hematologic malignancy were studied for their ability to synthesize immunoglobulin after in vitro stimulation with pokeweed mitogen, Herpes simplex type 1 antigen, tetanus toxoid, or Epstein-Barr virus. Purified T, OKT4, OKT8, or B cells from patients were cocultured with normal T and/or B cells in the presence of the various stimulants. Multiple regulatory defects were observed in long-term patients with and without chronic graft-versus-host disease. The lymphocytes from the long-term healthy chimeras exhibited fewer defects in their ability to regulate in vitro immunoglobulin synthesis than those of patients with chronic graft-versus-host disease. These findings suggest that the presence of chronic graft-versus-host disease delays or impairs the "rematuration" of the immune system after bone marrow grafting and that the rematurational process occurs at the clonal level.

Antibodies, Monoclonal↗
PubMed1983

Identification of immunoglobulin-secreting cells among canine peripheral blood mononuclear cells by the protein A hemolytic plaque assay.

Canine peripheral blood mononuclear cells (PBMC) were assayed for plaque-forming cells either immediately after isolation or after 6 days of culture in fetal calf serum in the presence of a B cell mitogen. Immediately-assayed PBMC produced a mean of 4870 IgG-related, 1610 IgM-related, and 760 IgA-related plaques per 10(6) PBMC. Many of the plaques formed by freshly isolated PBMC, however, appeared to represent release of previously adsorbed antibody. In contrast, plaques formed by cultured cells clearly identified immunoglobulin-secreting cells. We therefore used a system with culture conditions optimized for maximum plaque production to quantify pokeweed mitogen-stimulated plaque formation by normal canine PBMC. A mean of 560 IgG, 180 IgM, and 18 IgA plaque-forming cells could be identified among PMBC of 22 normal dogs. This assay will be useful for further characterization of canine lymphocyte subpopulations and facilitate the study of immunologic disorders in canine models.

Animals↗
PubMed1982

Immunoglobulin secretion by human B lymphocytes exposed to herpes simplex type I antigen.

Herpes simplex type I (HSV I) antigen was studied for its capacity to induce immunoglobulin(Ig)-secreting cells in human peripheral-blood lymphocytes. Ig-secreting cells were detected using an indirect hemolytic plaque assay. These results were compared to those obtained by using pokeweed mitogen (T-dependent) and Epstein-Barr virus (T-independent) to induce Ig-secreting cells. The HSV I induction of Ig synthesis was T-dependent, similar to the pokeweed-mitogen system. Peripheral-blood mononuclear cells depleted of T cells did not produce immunoglobulin. In contrast, the same T-depleted cell populations stimulated with Epstein-Barr virus (another member of the Herpes group) produced Ig. Lymphocytes in the HSV-I-stimulated cultures were found to secrete immunoglobulins of the IgA, IgG, and IgM classes. It was the lymphocytes from seropositive individuals that made Ig after HSV I stimulation. Such responses suggest that this system may be antigen-specific. This T-dependent virally induced Ig synthesis system may be useful in studying immunodeficient and immunocompromised individuals.

Antigens, Viral↗
PubMed1982

Bone marrow transplantation in the Wiskott-Aldrich syndrome. Complete hematological and immunological reconstitution.

A 21-month-old boy with the Wiskott-Aldrich syndrome conditioned with cyclophosphamide and dimethyl myleran received bone marrow from an HLA-matched sibling. Complete hematological chimerism was achieved. During the first 3 months after transplantation, in vitro B cell function, measured by a direct plaque assay, was abnormal, T cell helper activity impaired, and suppressor T cell function was excessive. These abnormalities resolved gradually over 16 months. Antibody responses to the T-dependent antigen, bacteriophage phi X174, were initially low, then became normal; antibody responses to keyhole limpet hemocyanin (KLH) and to 4 of 12 type-specific pneumococcal polysaccharide antigens were adequate when studied 9 months after transplantation. The clinical response was excellent: the patient has been free of infection, no longer has a bleeding tendency, and has shown normal growth and development.

Antibody Formation↗