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Biomedical subjects

T Umiel

Publications and source records attributed to T Umiel.

At least 37 records · Page 2Linked to original sources
PubMed1987

Undifferentiated leukemia of infancy with t(11:17) chromosomal rearrangement. Coexpressing myeloid and B cell restricted antigens.

It has been suggested that the malignant transformation, in some of the acute leukemias, may involve totipotent stem cells resulting in a biphenotypic leukemia expressing both myeloid, and lymphoid characteristics. We describe here a hybrid cell acute leukemia, in a 16-day-old infant, in whom leukemic cells coexpressed myeloid and lymphoid B cell antigens. Blast cells in the bone marrow showed L2 morphology according to the French American British (FAB) classification, with positive periodic-acid Schiff, and nonspecific esterase staining. Sudan black, and specific esterase were negative. Terminal deoxynucleotidyl transferase, was strongly positive in 5% of blasts, and faintly reactive with the rest. Karyotypic analysis demonstrated a translocation of t(11:17);(q23;p13). Immunoglobulin gene analysis revealed rearrangement of the heavy chain genes. The blasts' phenotype was HLA/DR+ B4+ My7+ My9+ common acute lymphoblastic leukemia antigen (CALLA) B1- T11-. Dual immunofluorescence staining using anti My7, and My9 fluorescein isothiocyanate, and anti B4 pycoerythrin conjugated monoclonal antibodies, and flow cytofluorometry, revealed a labeling pattern of 25% B4+; 10% to 15% My7+; 17% My9+; and 50% of cells coexpressing B4 My7, and My9 antigens. These results provide evidence for a hybrid leukemia with lymphomyeloblasts being part of a single clone, which may indicate the origin of this leukemic clone from a pluripotent (lymphoid/myeloid) stem cell.

Antibodies, Monoclonal↗
PubMed1987

Antibodies to HIV in Israeli hemophiliacs: relationship between serological profile and disease development.

We studied 66 Israeli hemophiliacs for antibodies to HIV in blood samples collected between 1978 and 1985. By May 1985, 2 had AIDS, 2 had ARC, 4 had lymphadenopathy with some immunologic dysfunction, and 58 were asymptomatic. Antibodies to HIV were detected in 40 (60.6%) patients, including all 8 with disease. Presence of HIV antibodies was significantly associated with receipt of non-heat-treated commercial factor VIII concentrates (NHT fac VIII) between 1980 and 1983. Thirty-eight of 45 (84.44%) patients treated with NHT fac VIII developed antibodies to HIV, compared to 1 of 16 (6.25%) treated with cryoprecipitates and fresh plasma only. Of 40 seropositive patients, 1 (2.5%) had antibodies by 1980, 4 (10%) by 1982, 14 (35%) by 1983, 10 (25.0%) by 1984, and 11 (27.5%) by May 1985. The decline in the rate of seroconversion can be attributed to the replacement of NHT fac VIII concentrate with heat-inactivated factor VIII (HT fac VIII) concentrate by November 1983. As of January 1984 only HT fac VIII was administered. Twenty-nine multitransfused thalassemia patients as well as 20 healthy Israeli blood donors were seronegative to HIV. All 40 (100%) seropositive hemophiliacs had antibodies to viral env gene encoded gp120/gp160 antigens. Twenty-four (60.05%) also had antibodies to viral gag gene encoded p24 and/or p55 antigens. While antibodies to gp120/160 persisted during the follow-up time, a loss of antibodies to p24/55 was observed in 5 of 16 (31.25%) seropositive patients from whom multiple samples were available. gp120/160 positive, p24/55 negative hemophiliacs had significantly lower absolute T-helper cell counts and reversed Th/Ts ratios when compared to gp120/160 p24/55 seropositive patients. Four of the 16 (25.0%) asymptomatic gp120/160 positive, p24/55 negative patients developed overt disease within 15 months of the last blood collection. The data suggest that exposure to HIV antigens is widespread among hemophiliacs in Israel, and can be attributed to receipt of NHT fac VIII concentrates prior to 1984. Antibodies to gp120/160 are of the most important diagnostic value while loss of antibodies to p24/p55 may be of prognostic value.

AIDS-Related Complex↗
PubMed1986

Leukemia of early infancy. Early B-cell lineage associated with t(4:11).

A case of infantile acute leukemia associated with translocation t(4:11)(q21:q23) is reported. This leukemia has a very poor prognosis, and this patient survived for only 9 months. The blast cell morphology was L1/L2 according to the FAB classification and showed a lymphoid appearance on transmission electron microscopy. The histochemical stains showed a pattern of periodic acid-Schiff positivity and variable alpha-naphtyl acetate staining. The cells were TdT-positive and surface-marker phenotyping was positive for Ia-like and B4 antigens but negative for CALLA, T-cell markers, myelocyte and monocyte markers. The leukemic cells represent a frozen state of a very early precursor, corresponding to the earliest recognizable stage of the B-cell lineage. This observation may contribute to the controversion regarding the cell origin of this unique leukemia associated with t(4:11), lymphatic versus null cell, early myeloid, or mixed, and points to the possibility of a very early B-cell lineage leukemia.

Antigens, Neoplasm↗
PubMed1986

Long-term culture of infant leukemia cells: dependence upon stromal cells from the bone marrow and bilineage differentiation.

Infant leukemia cells with 46XY,t(11; 17)(q23; p13) karyotype and a hybrid pre B myeloid phenotype (HLA-DR, (Ia), B4 and My7-positive and CALLA and T11-negative) and immunoglobulin heavy chain gene rearrangement were maintained in long-term culture for over 10 months. The in-vitro survival and growth of the leukemia cells were strictly dependent upon the presence of their autologous marrow stromal cells. The latter could be replaced by the 14F1.1 clone of preadipocytes derived from mouse bone marrow. Neither heterologous human marrow or foreskin fibroblasts nor fibroblast or endothelial like cell lines from mouse stroma could mimic the effect of autologous stroma or 14F1.1 adipocytes. The leukemia cells maintained their original phenotype throughout the 10-month culture period with either their autologous stroma or the 14F1.1 adipocytes. They could be induced to differentiate in two distinct directions. Phorbol myristate acetate induced adherence of the leukemia cells and development of macrophage properties. In contrast, conditioned medium from a hybridoma producing B-cell growth factor caused aggregation of the leukemia cells and expression of CALLA antigen and surface IgM. This bipotency of the leukemia cells and their dependence upon marrow stroma are properties in common with stem cells.

Bone Marrow Cells↗
PubMed1986

In vitro restoration by interleukin-2 (IL-2) of the impaired natural killer cell activities, IL-2 receptor expression, and T cell proliferation in hemophilia.

Five of 22 hemophiliacs who were seropositive for human T cell leukemia virus III (HTLV III) and manifested severe impairment of immune parameters (both in vivo and in vitro) similar to those observed in patients with clinical symptoms of acquired immune deficiency syndrome (AIDS) were chosen for this study. Profound lymphopenia was observed in four of five patients with decreased and qualitatively impaired helper/inducer (T4) cells and increased T suppressor/cytotoxic (T8) cells. Observed in all patients was impaired endogenous production of interleukin-2 (IL-2), expression of the IL-2 receptor combined with diminished responses to mitogens, mixed leukocytes reaction (MLR), and natural killer (NK) reactivity. In vitro supplement of exogenous IL-2 markedly augmented T and NK cell functions, as well as the expression of activation antigens on both T4 and T8 cell in four of five patients. Our findings suggest that a substantial proportion of this cell-mediated immunologic defect in hemophiliacs stems from their inability to produce adequate amounts of IL-2. Interleukin-2 may therefore have the potential for therapy as an immune response modifier in patients with hemophilia by providing beneficial preventive therapy for patients at risk.

Acquired Immunodeficiency Syndrome↗
PubMed1985

A mouse ear reaction for assessment of human lymphocyte immunocompetence.

A mouse ear reaction for testing cell mediated immunity of human lymphocytes using the local graft-versus-host reaction assay is described. Five million human mononuclears were locally injected into the ears of immune suppressed NZW mice. The reaction mounted was quantitated by determining the 125I-Iodo-Deoxyuridine (125I-UdR) incorporation in both ears. The ratio of 125I-UdR incorporation, of the injected to that of the non-injected ear (GVHR index), 7 days after lymphocyte injection, served as an accurate measure for the extent of the reaction. Only normal human mononuclears and purified, separated normal human T lymphocytes mounted a local graft-versus-host reaction. Whereas normal human B lymphocytes, chronic lymphatic leukemia B lymphocytes, mononuclears from patients with transitional cell carcinoma of the bladder, irradiated normal human mononuclears, mouse syngeneic mononuclears, or human erythrocytes gave no positive reaction. These experiments demonstrate that this assay can be used to quantitate an in-vivo specific graft-versus-host reaction.

Animals↗
PubMed1985

Lymphoid cells and granulocyte progenitors in early human fetal livers: immunological parameters and in vitro cellular interactions.

Human fetal liver (HFL) transplantations have been performed in infants with severe combined immunodeficiency and in patients with aplastic anemia, but the success rates have been extremely low, partly due to insufficient cell doses in grafts from a single donor. In order to explore the possible use of combining several HFL grafts from multiple donors, we studied immunological parameters as well as the in vitro responses of HFL cells from 20 fetuses, at 6 to 11 weeks of gestation, to allogeneic HFL cells and to adult lymphocytes in the mixed lymphocyte reaction (MLR), and the granulocyte-macrophage colony-forming cells (GM-CFC) assay. HFL cells of 6 to 11 weeks of gestation were found to lack populations of cells bearing surface markers of T- and B-lymphocytes and were capable of proliferating into lymphoid colonies. Virtually no MLR was found to allogeneic HFL cells or to adult lymphocytes [stimulation index (SI) 0.63 to 1.94], whereas adult lymphocytes responded normally to HFL cells (SI 3.9 to 62.0). Coculturing mixtures of allogeneic HFL cells in agar did not lead to suppression of the GM-CFC capacity of each liver. It appears that HFL at 6 to 11 weeks of gestation lack immunocompetent cells capable of provoking positive MLR in response to allogeneic HFL cells or to adult lymphocytes, and also capable of inactivating HFL-derived hematopoietic stem cells. This model may represent an in vitro counterpart for the in vivo pooling of HFL cells from multiple donors performed in order to increase graft cell dosage in man.

Adult↗
PubMed1984

Impaired immune regulation in children and adolescents with hemophilia and thalassemia in Israel.

The immune function was assessed in 22 children, adolescents and young adults with asymptomatic hemophilia, and 15 with thalassemia, in Israel. Five patients with hemophilia and two with thalassemia were found to be severely abnormal, having cutaneous anergy, very low T-helper cells, elevated T-suppressor cells, inverted T-helper/suppressor ratio, reduced response to mitogens and antigens, and nonfunctional NK cells. Four of the five hemophilia patients exhibited profound lymphopenia also. Decreased T-helper and mildly elevated T-suppressor cells with inverted T4/T8 ratio were observed in the hemophiliacs as a group. In the severe group, the reduction in T-helpers and T4/T8 ratio was more pronounced. The thalassemics as a group were found to have increased numbers of T-suppressor cells with decreased T-helper cells in those with intact spleen only. Both groups studied were found to have elevated IgG levels and low natural killer (NK) activity and normal response to mitogens. Cutaneous anergy was found to be a reliable indication for severe T-cell dysfunction and may serve as an early indication of impending AIDS. These results indicate that patients with hemophilia and with heavily hypertransfused thalassemia may be at increased risk of AIDS as they approach adolescence.

Acquired Immunodeficiency Syndrome↗
PubMed1984

THF, a thymic hormone, promotes interleukin-2 production in intact and thymus-deprived mice.

T cells stimulated by mitogen or antigen produce a T cell mediator, interleukin-2 (IL-2), which induces clonal expansion of activated target cells. The activity of IL-2 obtained from cell-free supernatants of spleen cells after 24-h incubation with concanavalin A was tested in an IL-2-dependent blast cell proliferation assay. IL-2 production was found to be diminished in neonatally thymectomized (NTx) mice. Treatment of NTx mice with a series of 14 daily injections of thymic hormone, THF (5-10 ng), resulted in reconstitution of IL-2 activity to the level found in intact, untreated mice. The rise in IL-2 activity was observed to be part of a general reconstitution of the immune capacity in the THF-treated NTx mice, manifested by elevated responses to mitogenic stimulation by T lectins and elevated mixed lymphocyte reactivity and cell-mediated cytotoxicity. Elevation of IL-2 activity could also be detected in vitro when spleen cells from intact mice were preincubated with THF for 24 h. THF did not enhance the production of interleukin-1 (IL-1) by bone marrow-derived macrophages, and in experiments in which T cells and macrophages were separately exposed to THF, augmentation of IL-2 activity was found only when the T cell-enriched spleen fraction was pretreated with THF. This was taken as proof that THF acted exclusively on T cells capable of producing IL-2, and that neither macrophages nor IL-1 were involved in the T helper activity induced by THF. Although THF could induce and/or augment IL-2 production by helper T cells, THF lacked IL-1 and IL-2 characteristics, since it could not maintain IL-2-dependent clonal expansion of target blasts nor induce IL-2 production by activated T cells.

Animals↗
PubMed1983

T cell progenitors in the mouse fetal liver.

Fourteen-day mouse fetal liver was found to contain cells capable of giving rise to T as well as B cell functions. The experimental system consisted of congenic C3H/DiSn and (C3H/DiSn X C3H.SW)F1 lethally irradiated (900 R) mice reconstituted with C3H/DiSn fetal liver or bone marrow cells. Assays included thyroid allograft rejection as well as in vitro measurement of reactivity to phytohemagglutinin (PHA) and concanavalin A (Con A) and in a mixed lymphocyte culture (MLC) system in spleen, lymph node, and thymus cells. The fetal liver chimeras were found to become as capable as the bone marrow chimeras in responding in these various assays. The T cell responses lagged behind the responses to the B cell mitogens dextran sulfate (DXS) and lipopolysaccharide (LPS) (30 days after reconstitution, as compared with 14 days for DXS and 21 for LPS). The reacting cells were of the donor genotype, as revealed after treatment with C3H/DiSn (H-2k) anti-C3H.SW (H-2b) congenic sera. T cell responses were not manifest in thymectomized (TX) chimeras. Hence, the liver seems to contain cells capable of developing into T cell lineages in a thymus-dependent process.

Animals↗
PubMed1983

Ontogeny of human hematopoietic cells: analysis utilizing monoclonal antibodies.

Lymphoid and myeloid cells isolated from second trimester fetal lymphoid organs were characterized by utilizing a panel of monoclonal antibodies that define human lineage-restricted, differentiation, histocompatibility, and activation antigens. At distinct gestational stages, the appearance of morphologically identifiable lymphoid and myeloid cells paralleled the appearance of cells expressing definable lymphoid and myeloid antigens. The proportion of cells in fetal liver, bone marrow, and spleen that expressed histocompatibility, myeloid, and B cell antigens increased with fetal maturation. In contrast, even the earliest fetal thymuses studied were of a phenotype no different than that seen during later stages of ontogeny. Although the cellular lineage of most fetal hematopoietic cells could be identified by this panel of reagents, a considerable number of fetal liver and bone marrow cells did not express any of these antigens, suggesting the possibility that they might represent early hematopoietic progenitor cells. These studies support the notion that the adult cellular phenotype is the result of both an orderly acquisition of differentiation antigens and the migration of these primitive cellular populations to specific fetal organs. Identification of hematopoietic progenitors in fetal tissues may facilitate the identification and isolation of early lymphoid and myeloid progenitor cells in adults.

Antibodies, Monoclonal↗
PubMed1982

Selective decline in differentiating capacity of immunohemopoietic stem cells with aging.

Bone marrow (BM) from young (3 months) and old (24 months) C57BL/6J mice were tested for the total number of colony forming units, which remain unchanged with age. The BM from both groups was used to reconstitute syngeneic, lethally irradiated mice that were 3 months' old. The reconstituted mice were followed for a period of 12 months for their ability to generate cell-mediated responses in mixed lymphocytic cultures and cultures containing the T mitogens--concanavalin A and phytohemagglutinin. For the first 8 months, mice given BM from young or old mice responded to a similar degree. Later, cellular immune responses of the mice reconstituted with BM from old mice declined markedly compared to those reconstituted with BM from young mice, although there was no detectable difference between the two groups in the hematopoietic compartment.

Aging↗
PubMed1982

Differences in the activity of adenosine deaminase and of purine nucleoside phosphorylase and in the sensitivity to deoxypurine nucleosides between subpopulations of mouse thymocytes.

The activities of adenosine deaminase (ADA) and of purine nucleoside phosphorylase (PNP) were measured in thymocyte subpopulations separated by peanut agglutinin (PNA), in unseparated thymocytes, in lymph node and in spleen cells. The PNA+ thymocyte subpopulation exhibited the highest ADA activity of all cells studied. The lowest PNP activity was found in the PNA- subpopulation of thymocytes. PNA+ cells, moreover, exhibited a more intensive DNA synthesis than the PNA- cells, and a greater sensitivity to deoxyadenosine toxicity in the presence of erythro-9-(2-hydroxy-3-nonyl)-adenine (EHNA). The two thymocyte subpopulations exhibited a similar sensitivity to deoxyguanosine (dG) toxicity.

Adenine↗
PubMed1982

Acquisition of immune competence by a subset of human cortical thymocytes expressing mature T cell antigens.

Previous studies indicated that the human thymus is composed of several discrete compartments. Cortical thymocytes are reactive with a monoclonal antibody, anti-T6 (TL-like) and coexpress antigens defined by antibodies anti-T4 and anti-T8. In contrast, most medullary thymocytes are unreactive with anti-T6, express either T4 or T8 antigens, and more importantly, brightly stain with anti-T3 and anti-T1, which define mature T cell antigens. Only a minor population of cortical thymocytes strongly express T1 and T3 antigens (T1+T3+). In the present study, we characterized this latter subpopulation of brightly staining T1+ cortical thymocytes. Because murine and human cortical thymocytes alone bear receptors for peanut agglutinin (PNA), cortical PNA+ thymocytes were separated from medullary PNA- thymocytes by fluorescence-activated cell sorting and were subsequently fractionated into PNA+T1+ (strongly anti-T1-reactive) and PNA+T1- (unreactive or weakly anti-T1-reactive) populations. The PNA+T1+ cells represented only 10 to 20% of thymic cortical lymphocytes. Whereas the PNA+T1- subset was unresponsive to PHA or alloantigen even in the presence of IL 2, the PNA+T1+ subset gave a brisk response to both stimuli on addition of IL 2. This latter response was similar to that of the PNA-T1+ medullary thymocytes. These results suggest that acquisition of mature T cell antigens is associated with immunocompetence despite a cortical localization.

Antigens, Surface↗
PubMed1981

Immune reactivity during ageing. III. Removal of peanut-agglutinin binding cells from ageing mouse spleen cells leads to increased reactivity to mitogens.

Spleen cells from ageing (24--30-month-old) mice, manifesting low response to concanavalin A (Con A) and phytohemagglutinin (PHA), were separated by peanut agglutinin (PNA) into agglutinable (PNA+) and unagglutinable (PNA-) fractions. The PNA+ cells were found to suppress the response of young (2--3-month-old) mouse spleen cells to the mitogens Con A and PHA. On the other hand, PNA- cells of the ageing mice expressed a response to these mitogens, at levels higher than those of the unseparated cells. Re-mixing of the PNA- and PNA+ cells of the ageing mouse spleens at various proportions indicated that the PNA- cells are indeed suppressible by the PNA+ cells. Anti Thy-1.2 treatment to the PNA+ fraction suggested that this suppression was not exerted by T cells. It thus appears that at least part of the reduced lymphoid cell function in ageing is related to an effect of suppressor cells, interfering with the expression of available reactive cells.

Aging↗
PubMed1979

Characterization of reactive and suppressive cells in the mouse embryonic liver by peanut agglutinin (PNA).

Embryonic liver cells suppressed the MLC response of adult mouse spleen cells and reactivity to mitogens Con A, PHA and LPS. Suppression was exerted by cells agglutinated by PNA (PNA+ cells). Cells reacting to LPS and to DxS were found in the nonagglutinated (PNA-) cell fraction. The PNA+ fraction did not react to DxS nor did it reduce the response of sdult spleen cells to this mitogen.

Animals↗