Biomedical subjects

S Raziuddin

Publications and source records attributed to S Raziuddin.

At least 55 records · Page 3Linked to original sources

PubMed1989

Severe T lymphocyte immunodeficiency associated with hypogammaglobulinemia: defective lymphokine secretion but enhanced autologous mixed lymphocyte reaction.

The multiparameter immunologic study of T cells of a patient with acquired hypogammaglobulinemia was investigated, since he had a normal B-cell number and function. His peripheral blood lymphocytes were found to contain predominant CD4+ CD45R+ T cells with a clear deficiency of CD4+ CDw29+ as well as CD8+ T cells. His T cells proliferated in response to phytohemagglutinin (PHA) and pokeweed mitogen (PWM), but no immunoglobulin was secreted in PWM-induced patient's T-cell and normal B-cell differentiations. His T cells were also found to possess concanavalin A (Con A)-induced suppressor function when cocultured with normal T cells, as well as IgG-, IgA-, and IgM-specific suppressor function on PWM-induced normal T- and B-cell differentiations. The patient's T cells were found to secrete elevated amounts of interleukin-2 but failed to secrete two important B-cell stimulating factors, B-cell growth factor and B-cell differentiation factor, in response to PHA. An investigation of immunoregulatory T-cell function in the autologous mixed lymphocyte reaction (AMLR) and allogeneic mixed lymphocyte reaction (MLR) indicated that the patient's T cells produced an enhanced AMLR but were deficient in MLR. These results suggest that the abnormalities we have identified in this patient with hypogammaglobulinemia reflect an intrinsic defect of T cells in the humoral immune response to produce three major immunoglobulins.

Agammaglobulinemia↗

PubMed1989

T-cell abnormalities in antibody deficiency syndromes.

We studied two patients with hypogammaglobulinaemia, three with selective IgA deficiency, and four with selective extreme IgM deficiency for T-cell abnormalities in the circulating blood. Most patients had altered CD4+ helper/inducer and CD8+ suppressor/cytotoxic T-cell subsets, and an elevated percentage of HLA-DR+ and interleukin 2 (IL-2) receptor+ antigens on lymphocytes. One patient with the selective IgA deficiency had an absence of CD4+ T cells in blood. The lymphocytes of eight patients showed a diminished proliferative response and deficient IL-2 production in response to stimulation with phytohaemagglutinin or concanavalin A. The three patients with selective IgM deficiency were found to have a defective T-cell abnormality in IgM synthesis by B cells. It is interesting that CD8+ T cells of the two patients with IgM deficiency demonstrated suppressor cell function for IgM synthesis by the normal B and T cells.

Agammaglobulinemia↗

PubMed1989

Selective loss of the CD4+ inducers of suppressor T cell subsets (2H4+) in active systemic lupus erythematosus.

We investigated 2H4+ and 4B4+ T cell subsets from the purified CD4+ helper/inducer and CD8+ suppressor/cytotoxic T cells in circulating blood of 15 patients with severe active systemic lupus erythematosus (SLE), 6 patients with inactive SLE, 5 patients with rheumatoid arthritis and seven healthy controls. The percentage of the total CD4+ T cells increased and CD8+ T cells decreased in all patients with active SLE. Of interest, however, all the patients with active SLE and central nervous system (CNS) disease had a selective decrease in the percentage of CD4+ 2H4+ T cell subsets in circulating blood that is responsible for induction of the CD8+ suppressor T cells. This loss of the CD4+ 2H4+ T cells was accompanied by an increase in the CD4+ 4B4+ T cell subsets, that are the true helper/inducers providing help for B cell immunoglobulin production. A marked decrease in the CD4+ 2H4+ cell subsets in the circulating blood of all patients with severe active SLE and CNS disease is related with meaningful functional properties of the T cells in an abnormal immune system.

Adolescent↗

PubMed1988

Transient T-cell abnormality in a selective IgM-immunodeficient patient with Brucella infection.

We describe here one 9-year-old female patient with an unusual form of selective IgM and CD4+ (OKT4+) helper/inducer T-cell immunodeficiency associated with Brucella infection. During the acute phase of Brucella infection, the percentage of infection. During the acute phase of Brucella infection, the percentage of peripheral blood lymphocytes (PBL) displaying OKT3+, OKT11+, and OKT4A+ phenotypes was decreased, and that of the OKT8+ cell was increased. These phenotypic T-cell abnormalities disappeared after antibiotic therapy in a 5-week period. However, the marked deficiency of CD4+ T cells and the IgM deficiency present during the acute phase of illness remained after recovery from illness. In vitro immunoglobulin production experiments during the acute phase of illness demonstrated that the patient's T cells lacked the capacity to provide helper/inducer function for normal B-cell differentiation to secrete IgM. The patient's T cells were also shown to possess IgM-specific suppressor cell activity on normal B- and T-cell differentiations. Thus impaired T-cell function was shown to be responsible for IgM-deficient antibody production. Defective interleukin 2 receptor expression and production by the patient's PBL in response to mitogenic stimulation also were present, indicating a severe defect in the patient's T-cell function.

Antibodies, Monoclonal↗

PubMed1988

OKT4+ T cell abnormality in patients with active systemic lupus erythematosus: HLA-DR antigen expressions.

The objective of this study was to define immunologic T cell abnormality characteristic of active systemic lupus erythematosus (SLE). Eight of nine patients who had severe clinical and laboratory manifestations of active SLE had a characteristically marked increase in OKT4+ and a decrease in OKT8+ T cells. Using OKIa1 and OKDR monoclonal antibody, we found that, in circulating blood of all patients with active SLE, an increased percentage of Ia+ and DR+ T cells is present compared to inactive SLE. Five of these active SLE patients had Tac+ antigens, an interleukin 2 receptor on OKT4+ and OKT8+ T cell subsets in resting blood. The present study demonstrates that Ia+ and DR+ antigens are selectively expressed on the majority of OKT4+ T cell subsets of all patients with active SLE, whereas Ia+ and DR+ antigens are expressed almost equally on both OKT4+ and OKT8+ T cell subsets in inactive SLE. The elevated percentage of Ia+, DR+, OKT4+ T cells in active SLE was accompanied by a highly depressed proliferative response to T cell mitogens, phytohemagglutinin and concanavalin A. However, OKT8+ T cell subsets in active SLE possessed a normal proliferative response to these T cell mitogens. We conclude that this abnormality of activated OKT4+ T cells bearing HLA-DR antigens may play a role in the development of active SLE.

Adult↗

PubMed1988

Phenotypic and functional T cell subset abnormalities in patients with aplastic anaemia and hypogammaglobulinaemia.

We have investigated T cell abnormalities present in blood of two patients with aplastic anaemia and hypogammaglobulinaemia. There was a marked increase in class II, major histocompatibility complex, HLA-DR+ antigen, and interleukin-2 receptor (Tac+) bearing CD4+ helper/inducer T cells, and a concurrent reduction of CD8+ suppressor/cytotoxic T cells. These CD4+ T cells produced an elevated proliferative response to phytohaemagglutinin and concanavalin A. Interestingly, the T cell subset mainly responsible for elevated production of the lymphokine, interleukin-2, under the stimulus of phytohaemagglutinin, was characterized as belonging to a CD4+ T cell subset. Functional studies, using a pokeweed mitogen driven IgG, IgA and IgM synthesis, demonstrated a correlation between CD4+ T cell deficient helper function for B cell differentiation and the clinical finding of the patient's hypogammaglobulinaemia.

Adult↗

PubMed1988

Functional properties of neoplastic T cells in helper T cell prolymphocytic leukaemia with IgM hypergammaglobulinaemia.

A case of T cell prolymphocytic leukaemia of helper/inducer T cell phenotype with IgM hypergammaglobulinaemia in a 65-year-old Saudi man is presented. The neoplastic T cells in the patient had an OKT3+, OKT4+, OKT8-, OKT11+, OKCLL+, OKIa1+, OKDR+, Tac+ phenotype. The presence of OKIa1+, OKDR+, and Tac+ antigens indicates that the leukaemic T cells were in an activated state. The cells responded to phytohaemagglutinin, but showed a diminished response to concanavalin A. The reduced interleukin 2 receptor expression and interleukin 2 production were associated with defective concanavalin A-induced proliferation. There was suppression of mixed lymphocyte culture reaction between the patient and two healthy donors in response to concanavalin A. In vitro immunoglobulin production experiments demonstrate that the leukaemic T cells provided an enhanced helper cell function to produce IgM, and suppressor cell function to produce IgG immunoglobulins by pokeweed mitogen-induced normal B lymphocyte differentiation. In this study we also found that the patient's T cells proliferate in response to lipopolysaccharides, thus providing the first evidence that leukaemic (OKT4+) T cells from a prolymphocytic leukaemia patient can be stimulated by lipopolysaccharides.

Aged↗

PubMed1988

Peripheral T cell lymphomas: an immunological study of seven unusual cases.

A multiparameter study of malignant lymph node cells and peripheral blood lymphocytes of seven patients with peripheral T cell lymphoma is presented. The results of monoclonal marker studies showed three cases of helper-suppressor T cell lymphoma (OKT4+, OKT8+), one case of suppressor T cell lymphoma (OKT8+), and three cases of helper T cell lymphoma (OKT4+). Immunophenotypic heterogeneity of neoplastic T cells with expression of pan-T antigens, OKT3+, and OKT11+ (erythrocyte rosetting+) was observed in most patients. Six of the seven cases tested showed Ia and DR antigens. No relationship was detected between patterns of reactivity with T cell reagents and histological types. When tested, the in-vitro malignant T cells of five patients proliferated in response to concanavalin A (Con A), but had poor response to phytohaemagglutinin. The interleukin 2 receptors showed maximum expression on Con A-activated T cells of five patients, and phytohaemagglutinin-activated T cells of one patient. The neoplastic T cells (OKT4+, OKT8+) of one patient studied had suppressor activity for IgG and IgA, and helper activity for IgM synthesis on pokeweed mitogen-induced normal B cell differentiations.

Adult↗

PubMed1988

OKT4+ T cell deficiency and an association of immunoglobulin deficiency in systemic lupus erythematosus.

A patient with systemic lupus erythematosus and selective serum IgA and IgM deficiency also had a deficiency of OKT4+, OKT4A+, OKT4B+, and OKT4E+ T cells in circulating blood. This deficiency of helper/inducer T cell subsets in blood was associated with impaired T cell responses to phytohaemagglutinin in vitro, and an impaired ability to produce IgA and IgM by the patient's B cells. The patient's OKT4+ (CD4+) T cell deficient population suppressed IgM synthesis by normal B and T cells.

Adult↗

PubMed1987

A monoclonal antibody and functional study of malignant T cells of a patient with suppressor-T-cell lymphoma.

We describe the immunologic characteristics of malignant T cells of a T-cell lymphoma patient. The neoplastic cells in lymph node expressed OKT3+, OKT11-, E-rosetting-, OKT4-, OKT8+, OKIa1+, OKDR+ suppressor-T-cell phenotype. Functionally, these malignant T cells did not respond to phytohemagglutinin, but produced a good response to concanavalin A. A defect in expression of interleukin 2 receptors was evident in phytohemagglutinin-activated T cells. In vitro immunoglobulin production experiments demonstrated that patient's malignant T cells possess helper function on normal B cells to produce IgM, and suppressor function to produce IgG.

Abdominal Neoplasms↗

PubMed1987

Unique immunological behaviour of CD8+ (suppressor T cell) leukaemia cells.

A patient with chronic lymphocytic leukaemia and elevated serum IgM antibody is described. A multiparameter surface marker analysis of his peripheral blood lymphocytes demonstrated a unique phenotype of OKT3-, OKT11+, E-rosetting+, OKT4-, OKT8+, OKIa1+, OKCLL+, OKDR+, Tac+, characterizing the disease as suppressor (CD8+) T cell chronic lymphocytic leukaemia. Because of the uncommon phenotype and the abnormal serum immunoglobulin pattern, in vitro functional assays were performed that showed decreased mitogenic response to the phytohaemagglutinin, but increased response to concanavalin A. However, these leukaemic T cells demonstrated phytohaemagglutinin-specific suppressor cell activity on normal blood lymphocytes. In vitro functional studies indicated that a defect in the patient's T cells may cause IgM hypergammaglobulinaemia. The regulatory function of the patient's T cells on immunoglobulin synthesis by normal B cells was found to be mediated by a soluble factor secreted from neoplastic T cells.

Antigens, Surface↗

PubMed1983

Lipopolysaccharides of the cyanobacterium Microcystis aeruginosa.

Lipopolysaccharides (LPS) of two isolates of Microcystis aeruginosa were extracted with phenol/water and purified. Cesium chloride gradient ultracentrifugation of these preparations yielded only one fraction. The LPS contained significant amounts of 3-deoxy-D-manno-octulosonic acid, glucose, 3-deoxy sugars, glucosamine, fatty acids, fatty acid esters, hexoses, and phosphate. Heptose, a characteristic sugar component of the polysaccharide moiety of LPS of most gram-negative bacteria was absent. Lipopolysaccharides and lipid A hydrolysate of LPS preparations were active in mouse lethality and Limulus lysate gelation. The lipid A moiety was slightly less active in toxicity and Limulus lysate gelation assays than the intact LPS. The LPS and lipid A moiety of the two isolates of M. aeruginosa were less active in toxicity in mice and Limulus test than LPS of Salmonella abortus equi.

Animals↗

PubMed1982

Prolonged suppression of experimental allergic encephalomyelitis in the Lewis rats: the effect of lipopolysaccharides.

The current investigations have revealed that Lewis rats preimmunized with BP in CFA, and after recovery from the first episode of EAE, developed a second mild attack of EAE after challenge with BP/CFA at specified times. However, preimmunization of Lewis rats with BP complexed to LPS in CFA protects animals for a longer time from a second attack induced by BP/CFA challenge.

Animals↗

PubMed1982

Immunosuppression of experimental allergic encephalomyelitis. III. In vitro evidence for induction of suppressor T lymphocytes in draining lymph node cells of animals immunized with myelin basic protein complexed to lipopolysaccharides.

We recently demonstrated that Lewis rats immunized with bacterial lipopolysaccharides (LPS) precomplexed to guinea pig myelin basic protein (BP) in complete Freund's adjuvant were less effective in inducing experimental allergic encephalomyelitis (EAE) than BP-immunized controls. When tested in vitro both lymph node cells (LNC) and spleen cells (SpC) of animals immunized with BP-LPS were less effective in proliferative responses to various mitogens, which included phytohemagglutinin, concanavalin A, purified protein derivative of tuberculin, LPS, and BP. Of importance immunization of rats with BP complexed to LPS results in the generation of cells in lymph nodes of these animals that suppress the mitogenic response of BP-immunized LNC and also SpC in mixed lymphocyte cultures. The suppressive effect of these cells in mixed lymphocyte culture reaction was found specifically in response to BP and to a lesser extent to LPS in LNC. SpC of BP-LPS immunized animals did not suppress the proliferative response to SpC of BP-immunized animals. Treatment of these LNC with antithymocyte serum and complement abolished this suppressive effect of LNC, suggesting that the immunoregulatory cells in LNC of BP-LPS immunized animals are suppressor T lymphocytes. The parallel between the in vitro induction of suppressor T lymphocytes in the draining LNC and the function of LPS in the development of EAE in Lewis rats suggests a possible immunologic significance of the effect.

Animals↗

PubMed1981

Binding of bacterial endotoxin (LPS) to encephalitogenic myelin basic protein and modulation of characteristic biologic activities of LPS.

Myelin basic protein, isolated from central nervous system tissue and an inducer of experimental allergic encephalomyelitis in animals, has been demonstrated to form a stable molecular complex with the lipid A region of gram-negative bacterial lipopolysaccharides (endotoxins). This binding of endotoxin with myelin basic protein results in generation of lower m.w. aggregates with decreased isopycnic density. A number of lipid A-induced characteristic properties of endotoxin, such as B lymphocyte proliferative response in C3H/St mice, complement activation of normal human serum, Limulus lysate gelation, and lethal effects in mice, are modified as a result of binding of myelin basic protein with lipopolysaccharides.

Animals↗

PubMed1981

Prevention of experimental allergic encephalomyelitis by bacterial lipopolysaccharides: inhibition of cell-mediated immunity.

The immunization of Lewis rats with bacterial lipopolysaccharides (LPS) precomplexed to guinea pig myelin basic protein (BP) in complete Freund's adjuvant inhibits the development of experimental allergic encephalomyelitis (EAE) in these animals. These protected animals fail to manifest significant in vivo delayed-type hypersensitivity skin tests and in vitro lymphocyte proliferative responses to BP. Our results indicated that LPS induces a nonspecific reduction in immune reactivity of BP in Lewis rats.

Animals↗

PubMed1981

Experimental allergic encephalomyelitis in Lewis rats: inhibition by bacterial lipopolysaccharides and acquired resistance to reinduction by challenge with myelin basic protein.

In 2-mo-old Lewis rats immunized with bacterial lipopolysaccharides (LPS) precomplexed to guinea pig myelin basic protein (BP), the clinical and histologic manifestations of experimental allergic encephalomyelitis (EAE) were diminished compared with BP-treated controls. Similarly, in animals immunized with BP and challenged with BP-LPS at the same time or as long as 5 days after, the immunization with BP also inhibited the disease. That this capacity to reduce the incidence of BP-induced EAE is a unique property of LPS was suggested by the fact that other negatively charged molecules, such as DNA, RNA, and dextran sulphate, were not effective in inhibiting the clinical signs of EAE. After recovery from EAE induced by BP, some animals develop a recurrence of the disease if challenged with BP at appropriate intervals. However, after recovery from mild EAE induced by BP-LPS and after challenges with EAE-initiating BP antigens, secondary EAE was inhibited significantly.

Animals↗

PubMed1980

Biological activities of chemically modified endotoxins from Vibrio cholerae.

Lipopolysaccharides from Vibrio cholerae, NIH 41, Ogawa 5321 and Inaba 66/64 were treated with succinic anhydride, phthalic anhydride and dinitrophenyl ethylene diamine, and the resultant derivatives, sodium succinyl lipopolysaccharide, sodium phthalyl lipopolysaccharide, and dinitrohpenyl lipopolysaccharide obtained respectively were investigated for various biological activities. The succinylation and phthalylation of lipopolysaccharide decreased the 3-hydroxy lauric acid, a major ester-linked fatty acid of these bacteria, and as a result of which these modified products exhibited lower toxic activities in chick embryos, mouse and in generalized local Shwartzmann reaction in rabbits than their parent lipopolysaccharides. The dinitrophenylation of lipopolysaccharide increased its toxicity in chick embryos and mice, but dinitrophenyl lipopolysaccharide was completely inactive in Shwartzmann reaction in rabbits. However, despite the loss of these biological activities, these modified derivatives of lipopolysaccharide retained and increased the activities in pyrogenecity and in various immunological properties.

Animals↗