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Biomedical subjects

M Divine

Publications and source records attributed to M Divine.

65 records · Page 4Linked to original sources

Failure of combination chemotherapy of advanced follicular (low-grade) non-Hodgkin's lymphoma.

Twenty-two patients with Stage III and IV follicular non-Hodgkin's lymphoma were treated for 8 months by a chemotherapy regimen alternating between two different four-drug combinations (doxorubicin, teniposide, cyclophosphamide, prednisone; vincristine, cyclophosphamide, CCNU, prednisone). The overall response rate (complete and partial remission) was 68%. The complete remission rate was 23%. Twenty patients are alive, 50% of them are free of disease progression (median follow-up 76 months). It is concluded that our chemotherapy regimen is not satisfactory and that new therapeutic approaches are needed.

Adult↗

Phenotypic and genotypic heterogeneity in large granular lymphocyte expansion.

The cellular heterogeneity of large granular lymphocyte expansions has been illustrated by the phenotypic and genotypic findings in five patients. In one patient whose circulating cells were CD2+, CD3-, CD5-, CD7+, CD8-, CD11+, Leu7+, CD16+, and displayed strong natural killer activity, no rearrangement of the T cell receptor beta-chain gene and T cell rearranging gene gamma was detected. The four other patients presented with neutropenia without overt lymphocytosis. In these patients the circulating lymphocytes expressed a predominant T cell phenotype CD2+, CD3+, CD5+, CD7+, CD8+, Leu7+. In three of them the presence of a T cell clone was demonstrated on the basis of a unique pattern of rearrangement of the T cell receptor beta-chain genes.

Aged↗

Vasculitis in hairy-cell leukemia.

Vasculitis associated with hairy-cell leukemia (HCL) has been reported occasionally. We determined the clinical and biological significance of this association by the retrospective study of a series of 50 patients with HCL, including nine patients with vasculitis. The development of vasculitis was not related to a variant of HCL on the basis of hematologic findings and survival. Vasculitis could occur at any time during the course of HCL, and was the circumstance for the diagnosis of HCL in three cases. Clinical and immunohistologic findings were those of hypersensitivity vasculitis in the nine patients. Infection was found to be an associated factor. Thus, eight of nine patients were infected at vasculitis onset, four died of their infection with no remittance of the cutaneous lesions, and three recovered from both infection and vasculitis. The monocyte deficiency in HCL is known to favor intracellular pathogen infection; however, we could not demonstrate that it also correlates with a decrease in the clearance of IgG-sensitized erythrocytes. Finally, vasculitis in HCL appears to be associated with a lasting infection in most cases.

Adult↗

Persistence of T8+/HNK-1+ suppressor lymphocytes in the blood of long-term surviving patients after allogeneic bone marrow transplantation.

Fifteen patients and their respective bone marrow donors were entered in this study 1 to 5 yr after allogeneic bone marrow transplantation. Peripheral blood E rosetting (T) cells were analyzed for their phenotypic characteristics as well as for their ability to regulate Ig synthesis in the in vitro PWM system. A close relationship was found between a high proportion of T8+/HNK-1+ cells and/or T8+/HLA-DR+ cells and a strong (greater than or equal to 50%) inhibition of the antibody response. It was noteworthy that even the patients without suppressor activity had high proportions of such cells when compared with normal marrow donors. Moreover, the suppression occurred irrespective of the presence or absence of chronic GVHD. Through negative selection experiments (with MAb and complement) and through immunofluorescence cell sorting, it was shown that the suppressor cells expressed the T8+, HNK-1+, HLA-DR- phenotype. They did not carry the Leu-11, NKH1A, or NKH2 determinants, which are expressed on mature functional NK cells. When examined by electron microscopy, they exhibited a morphology of resting agranular lymphocytes. The significant increase of these suppressor cells among the BMT patients was not correlated with clinical syndromes such as chronic GVHD or opportunistic viral infections, which argues against the notion of in vivo profound immunodeficiency coexisting with these cells.

Antibody Formation↗

Clonal T-cell colony formation in agar culture: an attractive assay to test the T-cell depletion from bone marrow.

Current studies suggest that the depletion of T-lymphocytes from donor marrow is an effective method for preventing acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation in man. To deplete the T-lymphocytes from bone marrow cells we use either monoclonal anti-T-cell antibodies and complement or T101 ricin A-chain immunotoxin. Residual T-lymphocytes are analyzed by their capacity to form clonal T-cell colonies in the presence of phytohemagglutinin (PHA), accessory cells, and recombinant interleukin 2. The method is compared to immediate indirect immunofluorescence (iF) and thymidine incorporation by marrow cells stimulated by PHA. IF is not suitable for evaluating the depletion by immunotoxin, and the interpretation of thymidine incorporation is generally questionable. The results of the colony formation show that the sensitivity of the colony assay is close to that of iF when T cells are depleted by complement lysis, and the sensitivity of the colony assay is not dependent upon the depletion procedure. Therefore, the T-cell colony assay is a simple functional control for the quality of bone marrow T-cell depletion, especially for T-cell depletion by immunotoxin.

Agar↗

A subset of OKT4+ peripheral T cells can generate colonies containing mixed progeny with OKT4+ helper and OKT8+ suppressor cells.

The membrane phenotype of human T cell colony progenitors and that of their clonal progeny was studied for expression of the T4 and T8 determinants. Using clonal culture conditions, the colonies were grown in semi-solid agar medium from peripheral blood cells. Clonality was assessed using the glucose-6-phosphate-dehydrogenase isoenzyme marker. Combination of this marker with the culture of sorted cell fractions allowed us to ascribe the colony progenitors to a subset of OKT4+ lymphocytes. The progeny consisted of the mixture of single OKT4+, single OKT8+ and double OKT4+8+ cells, as determined by double staining. Double staining was performed on mass-harvested colony cells and on individual colonies expanded in liquid culture with fresh interleukin 2. Expression of the OKT8 positivity on colony cells deriving from OKT4+ progenitors required an interaction with radioresistant OKT8+ cells that were co-cultured with these progenitors. Furthermore, the functional capacities of the cell progeny were assayed on the pokeweed mitogen-driven immunoglobulin production by B cells. It was found that OKT4+ colony cells were helper whereas OKT8+ colony cells were suppressor cells. It is concluded that a subset of OKT4+ peripheral blood T lymphocytes can generate colonies containing both helper OKT4+ cells and suppressor OKT8+ cells.

Antibody Formation↗

Human mononuclear phagocyte differentiation: a study of the U-937 cell line by ultrastructural cytochemistry and surface antigen analysis.

U-937 represents a well-established permanent human haematopoietic cell line, which exhibits characteristics of the monocyte/macrophage series. U-937 cells were investigated by peroxidase ultrastructural cytochemistry in order to determine the normal developmental stage to which they correspond. This study was performed in non- and TPA-stimulated cells, in conjunction with surface analysis by monoclonal antibodies. It is concluded: (1) peroxidase-positive U-937 cells are monoblasts and promonocytes involved in myeloperoxidase synthesis; (2) TPA-stimulation caricatures transformation of these cells into monocytes but not into resident macrophages, as far as peroxidase cytochemistry is concerned; (3) the reactivity of myeloperoxidase present in the endoplasmic reticulum of synthesizing cells is inhibited by glutaraldehyde fixation.

Antigens, Surface↗

Mechanism of accessory cell requirement in inducing IL 2 responsiveness by human T4 lymphocytes that generate colonies under PHA stimulation.

PHA-driven monoclonal colony formation by low concentrations of resting T4 lymphocytes in agar culture requires the presence of interleukin 2 (IL 2) and accessory cells. Using recombinant IL 2 and anti-Tac monoclonal antibody as a probe for the IL 2 receptor, we demonstrate that the requirement of accessory cells (here an irradiated B cell line) in inducing IL 2 responsiveness relies on their enhancing effect in functional IL 2 receptor expression by the T colony progenitors. Furthermore, it is shown that cell to cell interaction between accessory cells and colony progenitors results in IL 2 response, i.e., colony formation, when the IL 2 receptor density reaches a critical threshold. The asynchronism in IL 2 responsiveness expression by the T colony progenitors upon activation and the short-lived T cell-accessory cell interaction, due to accessory cell death, determine the 10% colony efficiency of the culture system. In addition, we demonstrate that the accessory function in IL 2 receptor and IL 2 responsiveness expression by the T colony progenitors can be supported by irradiated T lymphocytes as well as B cells. The absence of lineage restriction of the signal delivered by accessory cells, and the requirement of physical interaction between T colony progenitors and accessory cells, emphasize the necessity of cross-linking the activation-signal receptors in inducing IL 2 responsiveness by resting T4 cells.

Antibodies, Monoclonal↗

Phenotype study of fresh and cultured hairy cells with the use of immunologic markers and electron microscopy.

The phenotype of fresh and cultured leukemic cells from patients with hairy cell leukemia was studied using a panel of monoclonal antibodies in addition to the detection of peroxidase activity under electron microscopy. In fresh samples, the leukemic cells from 11 patients displayed predominantly a B phenotype, as judged by their reactivity with the B1 monoclonal antibody and surface immunoglobulin expression. Ultrastructural peroxidase activity, characteristic of hairy cells, was observed in all cases studied. When hairy cells were cultured in the presence of phytohemagglutinin and irradiated T cells, their phenotype converted from surface Ig+, B1+, OKT3-, OKT11- to surface Ig-, B1+, OKT3-, OKT11+. In contrast, the peroxidase activity remained unchanged. Some hairy cells were also OKM1+, but no conclusion could be made about the MO2 antigen, a more specific marker of monocytes. The variability of the phenotype in vivo and in vitro indicates that reliable markers are required for identifying hairy cells. When studied together, the staining by B1 monoclonal antibody and the ultrastructural detection of peroxidase, enable the identification of hairy cells with certainty.

Antibodies, Monoclonal↗

Peripheral T-cell lymphoma presenting as predominant liver disease: a report of three cases.

Three cases of a peculiar form of peripheral T-cell lymphoma presenting as predominant hepatic disease with splenomegaly are reported. The three patients had marked liver enlargement without lymphadenopathy; white blood cell count was normal, and modifications of hepatic tests were mild. In the three cases, the diagnosis of the lymphoma was mainly based on the results of hepatic morphological changes. Liver involvement was histologically characterized by a predominantly sinusoidal infiltration by tumor cells in the three cases, associated with perisinusoidal fibrosis in two of them; portal infiltration was noted in two patients. Immunopathological study showed that tumor cells were T-lymphoid cells that were different from normal T-lymphocytes by the lack of expression of one T-cell membrane antigen, i.e., Leu-1. These findings suggest that a distinct clinical, pathological and immunopathological entity might be individualized within the large group of T-cell lymphomas.

Adult↗

Evaluation of the BAX system for detection of Listeria monocytogenes in foods: collaborative study.

A multilaboratory study was conducted to compare the automated BAX system and the standard cultural methods for detection of Listeria monocytogenes in foods. Six food types (frankfurters, soft cheese, smoked salmon, raw, ground beef, fresh radishes, and frozen peas) were analyzed by each method. For each food type, 3 inoculation levels were tested: high (average of 2 CFU/g), low (average of 0.2 CFU/g) and uninoculated controls. A total of 25 laboratories representing government and industry participated. Of the 2335 samples analyzed, 1109 were positive by the BAX system and 1115 were positive by the standard method. A Chi square analysis of each of the 6 food types, at the 3 inoculation levels tested, was performed. For all foods, except radishes, the BAX system performed as well as or better than the standard reference methods based on the Chi square results.

Chi-Square Distribution↗