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M Divine

Publications and source records attributed to M Divine.

At least 55 records · Page 3Linked to original sources
PubMed1991

A simple, efficient washing procedure for cryopreserved human hematopoietic stem cells prior to reinfusion.

We describe our experience with a washing procedure used on cryopreserved, thawed bone marrow (BM) and peripheral blood stem cell (PBSC) grafts prior to autologous transplantation in 50 and 12 patients respectively. The procedure consists of a stepwise dilution with 2% human serum albumin and centrifugation performed either manually or using a blood cell processor (Cobe 2991). In vitro studies showed mean recoveries of 80.8% for BM nucleated cells and 73.9% for BM hematopoietic progenitors (CFU-GM). The corresponding recoveries for PBSC were 89.1 and 93.9%. After 4 h storage at +20 degrees C of the manipulated grafts, no significant loss of CFU-GM was observed. We conclude that the technique is simple and efficient for washing large numbers of hematopoietic stem cells. This method may avoid the clinical complications often arising with unwashed grafts.

Blood Cells↗
PubMed1990

Hepatosplenic T-cell lymphoma: sinusal/sinusoidal localization of malignant cells expressing the T-cell receptor gamma delta.

Peripheral T-cell lymphomas consist of a clinically heterogeneous group of malignant disorders whose immunophenotype usually corresponds to that of normal mature T cells. We describe and correlate the clinical, histopathologic, phenotypic, and genotypic findings in two patients with malignant lymphoma presenting with hepatosplenic disease. The morphologic pattern of lymphoma was that of a sinusal/sinusoidal infiltration in spleen, marrow, and liver. This morphologic characteristic was associated with the presence of a productive clonal rearrangement of the T-cell receptor (TCR) delta gene. Lymphoma cells expressed a CD3-TCR-gamma delta- phenotype. They were also double negative (ie, CD4-CD8-) and lacked the CD5 and CD7 antigens. In one patient, tumor progression was associated with phenotypic changes that resulted in a CD3-TCR-gamma delta- phenotype with the same delta-gene rearrangement as initially. These observations suggest the existence of a new type of peripheral T-cell lymphoma characterized by its hepatosplenic presentation, and by the sinusal/sinusoidal tropism and the TCR-gamma delta phenotype of the malignant cells.

Adult↗
PubMed1990

Polymerase chain reaction (PCR) amplification demonstrates the absence of human T-cell lymphotrophic virus (HTLV)-I specific pol sequences in peripheral T-cell lymphomas.

HTLV-I seronegative patients in nonendemic areas have been described with T-cell proliferations the DNA of which contains specific HTLV-I viral sequences. We have looked for the presence of HTLV-I DNA sequences in 27 HTLV-I seronegative patients with peripheral T-cell lymphomas, distinct from adult T-cell leukemia (ATL), and four HTLV-I seropositive patients, three with an ATL and one with a tropical spastic paraparesis. Using HTLV-I pol specific primers, the genomic DNA from peripheral blood mononuclear cells and lymph nodes massively infiltrated by tumor cells was analyzed by the enzymatic gene amplification procedure. In contrast to the peripheral blood lymphocytes from the four HTLV-I seropositive patients, the peripheral T-cell lymphoma samples did not harbor HTLV-I pol sequences. The data show that the detection of HTLV-I nucleotide sequences by the polymerase chain reaction correlates with serologic analysis in this series.

Base Sequence↗
PubMed1990

CD3-T cell receptor modulation is selectively induced in CD8 but not CD4 lymphocytes cultured in agar.

The CD3-T cell receptor (TcR) complex is central to the immune response. Upon binding by specific ligands, internalized CD3-TcR molecules increase, and either T cell response or unresponsiveness may ensue depending on the triggering conditions. Using semi-solid agar culture, we have shown previously that quiescent CD4 but not CD8 lymphocytes generate clonal colonies under phytohaemagglutinin stimulation. Here we have demonstrated that the agar induces selective CD3-TcR modulation in the CD8 and not in the CD4 subset. CD8 lymphocytes preactivated in liquid culture and recultured in agar with exogenous recombinant interleukin-2 generate colonies with a modulated CD3-TcR surface expression. The peptides composing the CD3-TcR complex are synthesized in CD8 colonies as well as in CD4; however, the CD3 gamma chain is phosphorylated at a higher level in CD8 colonies. A component of the agar polymer, absent in agarose, appears to be the ligand that induces differential CD3-TcR modulation in the CD8 subset. In contrast to agar culture, CD8 colonies can be derived from quiescent CD8 lymphocytes in agarose. These CD8 colonies express unmodulated CD-TcR. CD3-TcR modulation with anti-CD3 monoclonal antibody prior to culturing in agarose inhibits the colony formation. We conclude that given triggering conditions can result in both CD3-TcR modulation and inhibition of the proliferative response selectively in the CD8 lymphocyte subset and not in the CD4.

Agar↗
PubMed1990

Expression of the alpha/beta and gamma/delta T-cell receptors in 57 cases of peripheral T-cell lymphomas. Identification of a subset of gamma/delta T-cell lymphomas.

Fifty-seven cases of peripheral T-cell lymphoma were studied for cell expression of the T-cell receptor (TCR) chains, using monoclonal antibodies specific for the beta chain (beta F1) of the alpha/beta TCR, and for the delta chain (anti-TCR delta-1) of the gamma/delta TCR. Three different patterns were demonstrated: in 39 cases (69%), the phenotype (CD3+beta F1+TCR delta-1-) was that of most normal T cells. A second pattern was found on six cases (10%), which were of CD3+beta F1-TCR delta-1+ phenotype, and in which DNA analysis showed a clonal rearrangement of the delta locus in the five cases studied. It is suggested that these cases are the neoplastic counterpart of the small subpopulation of normal T cells that express gamma delta receptor. It is of considerable interest that these gamma delta lymphomas had unusual clinicopathologic presentations, as one case corresponded to a lethal midline granuloma and the five others to hepatosplenic lymphomas with a sinusal/sinusoidal infiltration in spleen, marrow, and liver. The fact that the distribution of the neoplastic gamma delta cells in the splenic red pulp resembles that of normal gamma delta cells reinforces the concept of a preferential homing of gamma delta T cells to this tissue. A third pattern (CD3 +/- beta F1-TCR delta-1-) was seen in 12 cases (21%), in which, by contrast to normal post-thymic T cells, no evidence of either alpha beta or gamma delta T cell receptor was found.

Antibodies, Monoclonal↗
PubMed1990

[Peripheral neuropathy and plasmocytic proliferations. Apropos of 17 cases].

Seventeen cases of peripheral neuropathy with plasmocytic proliferation were grouped together to analyze the clinical manifestations and evolution of this association of symptoms. The plasmocytic proliferation was 5 times that of multiple myeloma, 9 times that of a solitary bone plasmacytoma and 3 times that of a solitary plasmacytoma. The follow-up lasted 1 to 18 years (mean, 8 years) for solitary plasmacytomas. Other cutaneous and endocrinological symptoms, organomegaly and edema were sometimes present. The evolution was relatively severe, except in 6 patients whose solitary plasmacytomas were successfully treated with radiation. Six patients died 2 to 8 years (mean, 5 years) after the onset of neuropathy as a result of a progression of the neuropathy and/or anasarca (4 cases), or acute leukemia (2 cases) abetted by long-term chemotherapy. The therapeutic approaches available, the nature of the plasmocytic proliferation and its association with the neuropathy and the other symptoms are discussed.

Adult↗
PubMed1989

Mediastinal diffuse large-cell lymphoma with sclerosis: a condition with a poor prognosis.

Twenty patients (17 women, three men) with mediastinal diffuse large-cell lymphoma with sclerosis are reported. At the time of diagnosis, the disease was confined to supradiaphragmatic areas in all patients but two, who had kidney involvement (seven were stage I, 11 were stage II, and two were stage IV). A B-cell phenotype was demonstrated in nine of the 11 cases that were analyzed for cell lineage. All patients received an anthracyclin-containing regimen followed by mantle radiotherapy. Analysis of pretreatment characteristics showed that only the extent of disease influences outcome. Moreover, achievement of complete remission (CR) after chemotherapy appears to be a major prognostic factor. Two-year survival was better in patients who reached CR after chemotherapy than in those who did not (100% versus 9%; p less than 0.0001). Overall 2-year and 7-year survival rates were 50% and 33%, respectively. Therefore, localized mediastinal large cell lymphoma with sclerosis should be considered a high-risk subtype of non-Hodgkin's lymphoma in which standard treatment approaches are unsuccessful.

Adolescent↗
PubMed1989

Peripheral neuropathy, coagulopathy and nodular regenerative hyperplasia of the liver in a patient with multiple serologic auto-antibody activities and IgM B-cell lymphoma.

A patient with IgM-secreting B-cell lymphoma developed demyelinating peripheral neuropathy, nodular regenerative hyperplasia of the liver, coagulopathy, and terminal miliary lymphomatous spreading. Serologic auto-antibody activities directed against myelin associated glycoprotein, prothrombinase complex (i.e. lupus anticoagulant) and smooth muscle cells were detected. It is suggested that there is a link between the IgM gammopathy, the immunological abnormalities and the various clinico-pathological conditions.

Autoantibodies↗
PubMed1988

Lethal midline granuloma (polymorphic reticulosis) and lymphomatoid granulomatosis. Evidence for a monoclonal T-cell lymphoproliferative disorder.

Lymphomatoid granulomatosis (LG) and polymorphic reticulosis (PR), originally described as distinct entities, now are considered as a single disease process. Common histopathologic features include necrosis, vasculitis, and a granulomatous infiltrate. Such features have led to consider lymphomatoid granulomatosis as a systemic vasculitis; alternatively the possible emergence of an overt lymphoma has suggested that it could be a lymphoproliferative process. To investigate this later hypothesis, the authors analyzed the cellular infiltrate of tissue specimens from two patients with histologic features of LG. The analysis included the study of T-cell antigen expression and DNA rearrangement of the beta T-cell receptor gene. In one patient, the T-cell phenotype of infiltrating cells was abnormal because of antigen loss. In both patients, the cells contained rearranged DNA indicating the presence of a clonal T-cell proliferation. It is concluded that some cases of LG and PR, if not all, are related to a neoplastic T-cell lymphoproliferative disorder.

Adult↗
PubMed1988

Activation by PHA of CD8 lymphocytes into clonal colony forming cells. Role of interleukin-1.

Monoclonal T cell colonies can be grown in agar culture from quiescent T lymphocytes under PHA stimulation, provided that (1) a low number of T lymphocytes (less than or equal to 5 X 10(4)/ml) is seeded, (2) IL-2 is added to the culture, and (3) a high number of accessory B cells (greater than or equal to 5 X 10(5)/ml) is present in contact with the T lymphocytes. Under these culture conditions the colony progenitors can be ascribed to the CD4 subset, whereas CD8 lymphocytes do not generate colonies. This finding is surprising since both CD4 and CD8 lymphocytes may be cloned in liquid culture. We now report the appropriate conditions required to grow cytotoxic CD8 lymphocyte colonies in agar. CD8 colony growth is dependent upon IL-2-IL-2 receptor interaction and is inhibited by anti-IL-2 receptor antibodies. In addition to PHA, accessory B cells and IL-2, an additional signal provided by recombinant IL-1 is necessary for CD8 colony formation. Exogenous IL-1 can be replaced by irradiated CD4 lymphocytes which stimulate the expression of membrane IL-1 activity in the accessory B cells. In addition, colony growth from quiescent but not preactivated CD8 lymphocytes is inhibited by anti-IL-1 antibodies. Altogether, the data show that an IL-1 signal is required for the induction of IL-2 responsive IL-2 receptors on quiescent CD8 colony forming cells.

Animals↗
PubMed1988

Functional analysis of CD8 lymphocytes in long-term surviving patients after bone marrow transplantation.

The recovery of T-cell populations after bone marrow transplantation (BMT) is characterized by a persistent expansion of CD8 lymphocytes. Previously, we have shown that beyond 1 year posttransplantation the CD8 lymphocytes consist, to a large extent, of CD8+ HNK1+ cells that suppress, like normal CD8 lymphocytes, immunoglobulin production in vitro. We have further investigated the functional capabilities of CD8 lymphocytes, mostly HNK1+ (from 50 to 77%), in seven long-term BMT patients. As normal, patient CD8 lymphocytes do not suppress (1) phytohemagglutinin (PHA)-induced interleukin 2 (IL2) receptor expression and IL2 responsiveness by normal T cells or (2) the mixed lymphocyte reaction of donor cells. Also as normal, patient CD8 lymphocytes can be activated into potent cytotoxic effectors. Therefore, under the present experimental conditions, the increase in the absolute number of CD8 lymphocytes in the long-term BMT patients is characterized by an expansion of the CD8+ HNK1+-cell subpopulation and a normal suppressor/cytotoxic potential on a per-CD8+ cell basis.

Bone Marrow↗
PubMed1988

Hairy cell leukemia associated with large granular lymphocyte leukemia: immunologic and genomic study, effect of interferon treatment.

The authors describe a patient who presented an association of hairy cell leukemia (HCL) and large granular lymphocyte (LGL) leukemia. An eventual relationship between these two rare entities is analyzed. Hairy cells (HCs) were present in the blood, bone marrow, and spleen. An excess of LGLs was found only in the blood and bone marrow. After splenectomy the patient received an alpha 2-interferon (alpha 2-IFN) treatment. The HCs surface phenotype was mu+delta+kappa+, CD20+, and CD25+. The LGLs consisted in CD3+, CD8+, HNK1+, WT31+ T lymphocytes. These were absent in the spleen. alpha 2-IFN treatment resulted in the disappearance of the HCs in the blood and bone marrow, whereas the LGLs remained unchanged. Before alpha 2-IFN treatment, peripheral blood cells, predominantly LGLs, exerted low cytotoxicity that increased up to a normal level after treatment. Using Southern blotting the authors studied the rearrangements of the T-cell receptor beta--chain (C beta) and gamma-chain (J gamma) genes and immunoglobulin heavy (JH)- and light (C kappa, C lambda)- chain genes. An unique JH and C kappa gene rearrangement was found in the blood and spleen, whereas C beta and J gamma gene rearrangements were present in the blood, not in the spleen. Under alpha 2-IFN treatment, the JH gene rearrangement fainted dramatically, in contrast to that of the C beta gene. The study of messenger RNA (mRNA) of the T cell receptor alpha and beta chains evidenced the 1.3-kilobase (kb) and 1.6-kb bands in the blood and their absence in the spleen. The patient was human T-cell leukemia virus (HTLV)-II negative by Southern analysis of blood and spleen cells. It is concluded that the LGL expansion was clonal and not reactive to the HCL. Although the authors cannot definitely exclude that both HC and LGL proliferations stem in a common leukemic precursor, their findings support an association of the two entities.

Antigens, Surface↗
PubMed1988

Comparison of genetic probe with immunophenotype analysis in lymphoproliferative disorders: a study of 87 cases.

We examined 91 specimens (from 87 patients) for the expression of B-cell- and T-cell-associated differentiation antigens and rearrangements of the Ig and beta-chain of the T-cell (beta-TCR) genes. Of these, 74 were representative of various histologic subtypes of non-Hodgkin's lymphoma and related disorders, 11 of Hodgkin's disease, and 6 of reactive lymphoid hyperplasia. An Ig gene clonal rearrangement correlated to a monotypic (kappa/lambda) phenotype in 32 of 33 histologically defined lymphoma samples. The genotypic analysis also confirmed clonality in six of seven malignant diffuse lymphomas that were nonmonotypic but expressed pan-B antigens; in four, more than one clone was detected within individual tumors. A beta-TCR clonal rearrangement was found in 19 of 19 tumor samples considered as malignant T-cell lymphoma on the basis of histopathology and of the CD3-positive phenotype of tumoral cells, and in two cases of CD3-positive lymphomatoid disorders. A loss of pan-T antigens (CD7, CD5, CD2, CD4/CD8) was observed in all but three of these CD3-positive samples. Such an incomplete T-cell phenotype always correlated to the presence of a monoclonal process as revealed by genotypic analysis. DNA analysis was the only way to demonstrate clonality in other samples with either a polymorphous (partial involvement, pseudolymphoma, angioimmunoblastic lymphodenopathy [AILD]) or an undifferentiated (large cell anaplastic) phenotype. It is concluded that although in the majority of cases immunophenotyping alone provides criteria adequate for the diagnosis of lymphoid malignancy, in some, particularly polymorphous or large cell anaplastic processes, genetic probe analysis was additionally discriminative.

Antigens, Differentiation↗
PubMed1987

Persistent remission of adult chronic autoimmune thrombocytopenic purpura after treatment with high-dose intravenous immunoglobulin.

Transient efficacy of high-dose intravenous immunoglobulin infusions (HDI) is widely demonstrated in autoimmune thrombocytopenic purpura (AITP). A trial involving repeated injections of HDI was conducted in two adult patients with chronic AITP in order to evaluate their long-term efficacy in refractory forms and their ability to obviate splenectomy. Both patients received 2 g/kg body weight of polyvalent intact intravenous immunoglobulin followed by seven and eight boosters (0.8 to 1.2 g/kg body weight) when the platelet count decreased. It was found that the injections could be spaced progressively. The platelet count remained normal 200 and 800 days after the end of the treatment. The demonstration of the possible long-term efficacy of repeated injections of intravenous immunoglobulin encourages us to recommend this safe therapy for patients with chronic AITP.

Adult↗