Biomedical subjects

A Sheikha

Publications and source records attributed to A Sheikha.

8 recordsLinked to original sources

PubMed1998

Regulation of interleukin-4 production and cytokine-induced growth potential in peripheral T-cell non-Hodgkin's lymphomas.

The malignant cells in tumour tissues produce cytokines/growth factors that may influence tumour growth, tumour immunogenicity and host immune response. We demonstrate that lymph node cell (LNC) purified neoplastic T cells from CD4+ peripheral T-cell lymphoma (CD4+ PTCL) and CD8+ PTCL spontaneously, and after stimulation with anti-CD3, secreted high amounts of interleukin-4 (IL-4) as compared to LNC-purified CD4+ and CD8+ non-malignant T cells. Furthermore, IL-4 was observed to be the most potent cytokine that induced in vitro proliferation and growth of the malignant T cells. Moreover, malignant T-cell-derived IL-4 secretion was augmented by exogeneous recombinant human interferon-gamma (IFN-gamma) and was profoundly inhibited by IL-2. Because IL-4 was shown to be a locally active cytokine with a wide range of immunoregulatory properties, regulation of IL-4 production by IFN-gamma and IL-2 in malignant T cells may be one of the important parameters to be assessed in the design of anticancer-specific immunotherapy. In summary, we report that malignant T cells produce IL-4, a type 2 cytokine (Th2 cell response) that acts as a growth factor and which may play a critical role in PTCL disease mechanism.

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PubMed1994

Peripheral T-cell lymphomas. Immunoregulatory cytokine (interleukin-2, interleukin-4, and interferon-gamma) abnormalities and autologous mixed lymphocyte reaction.

BACKGROUND: Cytokines are the most important secretions of the immune system and have a wide range of immunoregulatory functions in various immune disorders and T-cell malignancy. The authors have determined that characteristic enhanced autologous mixed lymphocyte reaction (AMLR) of the lymph node-derived malignant T-cells from peripheral T-cell lymphomas is a function of the T-cell derived cytokines interleukin (IL)-2, IL-4, and interferon-gamma (IFN-tau). METHODS: Autologous mixed lymphocyte reaction assay was performed by the standard proliferative response (3H-thymidine incorporation), by culturing autologous lymph node-derived or blood-purified T-cells with autologous blood-purified mitomycin-c treated non-T-cells. The production of IL-2, IL-4, and IFN-tau in the AMLR cultures was determined by bioassay or enzyme immunoassays. RESULTS: Enhanced IL-2 and IFN-tau but deficient IL-4 production is the most characteristic and unique feature of the augmented AMLR in peripheral T-cell lymphomas. CONCLUSION: The immunoregulatory aberrations in lymph node-derived malignant T-cells that produce highly elevated IL-2 and IFN-tau but decreased IL-4 during augmented AMLR may play an important role in immune dysfunction in this neoplasm (peripheral T-cell lymphomas).

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PubMed1994

Circulating levels of cytokines and soluble cytokine receptors in various T-cell malignancies.

BACKGROUND: Cytokines, interleukin (IL)-4, IL-6, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), soluble CD23 (sCD23), and soluble IL-2 receptors (sIL-2R) are mediators of inflammation and immune response. Alterations in immune status of patients with various cancers may result in release of cytokines in circulation. The authors measured the circulating levels of IL-4, IL-6, IFN-gamma, TNF-alpha, sCD23, and sIL-2R from patients with T-cell chronic lymphocytic leukemia (T-CLL), T-cell acute lymphoblastic leukemia (T-ALL) and peripheral T-cell lymphoma (PTCL) to determine their importance in these T-cell disorders. METHODS: IL-4, IL-6, IFN-gamma, TNF-alpha, sCD23, and sIL-2R levels were measured from the serum samples by enzyme-linked immunosorbent assay or bioassay methods. RESULTS: IL-4 levels were higher only in T-CLL, whereas, IFN-gamma and sIL-2R levels were higher in T-CLL and T-ALL. However, IL-6, TNF-alpha, and sCD23 levels were higher in PTCL. CONCLUSIONS: T-cell-derived IL-4 and IFN-gamma in T-CLL may act as an autocrine growth factor for proliferation of neoplastic T-cells. The sIL-2R levels in T-CLL, T-ALL, and PTCL are an indication of the degree of T-cell or immune activation due to concomitant immunologic processes in these disorders. However, IL-6, TNF-alpha, and sCD23 levels may contribute to inflammatory response and provide evidence of monocyte/macrophage, T-cell, or B-cell aberrations in PTCL.

Adolescent↗

PubMed1993

Peripheral T-cell lymphoma with unique immunologic features.

BACKGROUND: The autologous mixed lymphocyte reaction (AMLR) is an important immunoregulatory phenomenon in human immune disorders. The authors have determined the phenotype and assessed the response of malignant lymph node T-cells, from histologically and immunologically proven cases of peripheral T-cell lymphoma, in AMLR and allogeneic mixed lymphocyte reaction (MLR) and studied the secretion of lymphokines. METHODS: The proliferative response, tritiated 3H-thymidine incorporation assay, was used to determine the AMLR and allogeneic MLR of the responding T-cells. An interleukin-2 (IL-2)-dependent T-cell line (CTLL) was used for the production of IL-2 by phytohemagglutinin-stimulated T-cells in a cytotoxic assay. B-cell growth and differentiation factor activity of T-cells was studied by enzyme-linked immunosorbent assay. RESULTS: The AMLR of malignant lymph node T-cells was increased characteristically in 12 of the 14 lymphoma cases studied; however, that of the blood T-cells was decreased. The allogeneic MLR of the malignant lymph node T-cells and blood-purified T-cells of the eight cases investigated was decreased. Expression or deficiency of CD2 and CD3 antigens on malignant T-cells did not show any difference in the AMLR assay. CONCLUSIONS: This study demonstrates an important tendency of malignant T-cells from patients with peripheral T-cell lymphoma to proliferate in AMLR. The highly augmented AMLR but deficient allogeneic MLR observed in these malignant T-cells indicate that autologous recognitive events may play an important role in the immunopathogenesis of this human disease.

Adult↗

PubMed1993

Visceral leishmaniasis: II. Histiocyte ultrastructure in bone marrow associated with low level of parasitaemia and mimicking malignant histiocytosis.

The ultrastructural features of histiocytes in the bone marrow (BM) were studied in a febrile, splenomegalic and pancytopenic Sudanese patient who was diagnosed by one of us as visceral leishmaniasis (VL) associated with low level of parasitaemia and mimicking malignant histiocytosis (MH). Serial thick (STS) and ultrathin (SUT) sections showed that the BM was hypercellular and markedly infiltrated by large histiocytes with prominent phagocytosis. A thorough examination of various ST and UT section revealed only a single, typical Leishman-Donovan body. At transmission electron microscopy (TEM) level, two principal types of histiocytic cells were identified: Type I, subdivided into two subtypes, were actively phagocytic histiocytes (PH) with large digestive vacuoles and primary lysosomes; type II were nonphagocytic histiocytes (nPH) with primary lysosomes only. The rate of PH to nPH ws 7:2 in plastic STS. The interaction between the PH and ingested cells is described. Both types of cell were morphologically similar to previously described malignant histiocytic cells. However, this study showed a better characterization of PH during VL.

Adult↗

PubMed1992

T-cell chronic lymphocytic leukemia. T-cell function and lymphokine secretion.

The leukemic T-cells of the six patients with T-cell chronic lymphocytic leukemia (T-CLL), four with CD4 and CD45R-positive (CD4+ CD45R*) T-CLL and two with CD8 and CD45R-positive (CD8+ CD45R+) T-CLL phenotype were studied for detailed immunologic phenotypic and functional characteristics. The levels of soluble interleukin-2 receptors were elevated significantly in the serum of all four patients with CD4+ CD45R+ T-CLL. Moreover, the CD4+ CD45R+ T-CLL patients' T-cells, after in vitro stimulation with phytohemagglutinin and concanavalin A, expressed elevated percentages of interleukin-2 receptors on cells and secreted high interleukin-2 activity. The B-cell growth factor (BCGF) activity from three patients with CD4+ CD45R+ T-CLL was enhanced, but B-cell differentiation factor (BCDF) activity of the all T-CLL patients was decreased. Reduced BCGF and BCDF activity of the leukemic T-cells was one possible mechanism of hypogammaglobulinemia detected in two patients with T-CLL. All T-CLL patients' leukemic T-cells had diminished immunoregulatory functional activity in allogeneic mixed lymphocyte reactions. These observations suggest that leukemic T-cells from T-CLL patients have many immunologic functional defects that may be important in their proliferative potential.

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PubMed1992

Otological manifestations of thalassaemia intermedia: evidence of temporal bone involvement and report of a unique cholesteatoma-like lesion.

Thalassaemia intermedia should be considered in any chronically anaemic patient presenting from the Middle East with hearing impairment. We report here three Saudi siblings with thalassaemia intermedia and features of severe bone marrow expansion, particularly invading the temporal bone. They were seen first for their otological problems before they had access to proper haematological evaluation. One member was admitted for surgical exploration of a cholesteatoma, which was then found to be marrow expansion of the temporal bone. Screening of the family revealed two more anaemic siblings with thalassaemia intermedia. Audiological examination of all the family members showed that only the two affected members had a high frequency sensori-neural hearing loss. Bone marrow expansion into the temporal bone is a rare feature of thalassaemia intermedia. Cholesteatoma-like lesion has not been previously described. It has to be considered in all cases of symptomatic thalassaemia intermedia manifesting with cavitation and lytic lesions in the mastoid system. The likelihood that sensorineural hearing loss may complicate the thalassaemias is raised and the possible mechanism for such involvement discussed. The proper management for different otological manifestations of the thalassaemias is suggested. These cases would suggest a more extensive involvement of the temporal bone in the thalassaemias than has been previously recognized. Further large scale studies are required to illuminate the subject.

Adolescent↗

PubMed1991

Humoral immunodeficiency in T-cell chronic lymphocytic leukemia. An immunologic assessment.

The humoral antibody immunodeficiency in two patients with T-cell chronic lymphocytic leukemia (T-CLL) appeared to be the result of immunoregulatory abnormalities in the leukemic T-cell populations. Both patients had CD4+ CD45R+ "virgin" or suppressor-inducer T-CLL, but Patient 1 had hypogammaglobulinemia and Patient 2, immunoglobulin (Ig) M hypergammaglobulinemia. Although, CD25+ interleukin-2 (IL-2) receptors were present on leukemic T-cells of both patient, OKT9+ (CD71) transferrin receptors and OKT10 (CD38) activation antigens were found only on Patient 2's cells. Highly elevated amounts of IL-2 was secreted from phytohemagglutinin-stimulated and concanavalin A-stimulated T-cells in both patients. In Patient 1 with hypogammaglobulinemia, immune defects involve T-cells, first an intense suppressor activity on B-cell-induced IgM and IgG synthesis and, second, deficient production of B-cell growth factor (BCGF) and B-cell differentiation factor (BCDF). In Patient 2, highly elevated BCGF and IgM-specific BCDF was secreted by T-cells, a mechanism leading to IgM hypergammaglobulinemia in this patient. These studies stress the importance of BCGF and BCDF activity of leukemic T-cells in humoral antibody immunodeficiency disorders in T-CLL cases.

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