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Biomedical subjects

G Majumdar

Publications and source records attributed to G Majumdar.

At least 37 records · Page 2Linked to original sources
PubMed1993

Temporal relationship of cytokine release by peripheral blood mononuclear cells stimulated by the streptococcal superantigen pep M5.

We undertook this study to determine the quality, quantity, and temporal relationship of pep M5-induced cytokine release. The ability of pep M5 to stimulate interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-alpha) production by a T-cell-depleted, monocyte- and B-cell-enriched cell population was dependent on the presence of T cells. The requirement for T cells could be met by addition of exogenous gamma interferon (IFN-gamma). In the presence of IFN-gamma, pep M5 induced the release of TNF-alpha, IL-1, and IL-6, TNF-alpha levels peaked at 24 h, while IL-1 and IL-6 levels peaked at 48 h. pep M5 induced T cells to produce IFN-gamma, which may have accounted for the ability of the super antigen to induce the production of IL-1, IL-6, TNF-alpha, and TNF-beta by peripheral blood mononuclear cells (PBMC). The addition of excess IFN-gamma to cultures of pep M5 and PBMC did not further increase the release of these cytokines at 24 and 48 h but resulted in sustained higher levels at 72 h. Interestingly, TNF-beta production occurred only in the presence of pep M5 and exogenous IFN-gamma. The ability of pep M5 to induce cytokine production was compared with that of a potent super antigen, staphylococcal enterotoxin B (SEB). SEB was a 2- to 14-fold-more-potent inducer of IFN-gamma production. Furthermore, the profile of cytokine released by PBMC in response to this super antigen mimicked that seen with pep M5 in the presence of exogenous IFN-gamma. In conclusion, pep M5 induces the production of cytokines that are involved in immune regulation and inflammation. These cytokines also play a major role in human T-cell responses to this super antigen.

Adult↗
PubMed1993

Renal failure caused by leukaemic infiltration in chronic lymphocytic leukaemia.

A case of B-CLL which was complicated by chronic renal failure due to leukaemic infiltration of the kidney is reported. Treatment with chlorambucil, prednisolone, and renal bed irradiation resulted in a substantial improvement in renal function which persisted until the the patient's death from marrow failure some eight years later. The temporal association between treatments and response suggested that renal bed radiotherapy had contributed to the improvement in renal function. This case is one of only two reported cases in which chronic renal failure due to CLL has been treated with radiotherapy. It is unique in that the renal response was shown histologically. Leukaemic infiltration of the kidney is common in CLL but, characteristically, is not associated with renal impairment. An improvement in renal function has been described in two patients with acute renal failure after chemotherapy.

Chlorambucil↗
PubMed1993

Waldenström's macroglobulinaemia terminating in acute myeloid leukaemia: report of a case and review of the literature.

We report on a patient originally diagnosed as having monoclonal gammopathy of undetermined significance (MGUS) who progressed to develop Waldenström's macroglobulinaemia (WM) after 3 years. Four years later he developed chronic myelomonocytic leukaemia (CMMoL) which terminated in acute myeloid leukaemia (AML) after another year. We also review published reports of similar cases.

Humans↗
PubMed1993

Clinical spectrum of autoimmune haemolytic anaemia in patients with chronic lymphocytic leukaemia.

Autoimmune haemolytic anaemia (AIHA) is a frequent complication of chronic lymphocytic leukaemia (CLL). The course of AIHA in CLL is quite variable and unpredictable. We report 9 patients who showed three distinct clinical patterns. Three patients had a single episode of AIHA which responded rapidly to oral prednisolone. Three others had a relapsing course often associated with a rising lymphocyte count which responded to a combination of prednisolone and cytotoxic drugs. The remaining three patients showed very little response to either form of treatment and continued to have haemolytic anaemia for the remainder of their lives. Development of AIHA did not appear to be associated with any particular stage of the disease and only patients with the third type of AIHA seemed to have a short survival.

Aged↗
PubMed1993

Serum erythropoietin and circulating BFU-E in patients with multiple myeloma and anaemia but without renal failure.

In 30 patients with multiple myeloma (MM) and mild to moderate anaemia (mean Hb 107 g/l, 95% confidence limit (CL) 102-113) but no evidence of renal failure (serum creatinine < 110 mumol/l), serum erythropoietin (EPO) showed significant inverse logarithmic correlation with the haemoglobin level (r = -0.57, p = 0.001). The observed/expected ratio of log-EPO in patients with MM (mean 0.96, CL 0.89-1.04) was similar to that of 119 subjects (mean 1.01, CL 0.96-1.05) with or without anaemia (mean Hb 116 g/L, CL 110-121) but without renal failure. The concentration of circulating erythroid progenitors (BFU-E) in 10 MM patients in plateau phase was significantly reduced (mean 0.70 x 10(5)/l of blood, CL 0.34-1.06) compared to that of 8 normal controls (mean 3.57, CL 1.60-5.55, p = 0.011) In vitro sensitivity of the BFU-E to EPO in the patients with MM was comparable to that of the normal controls. It appears that in MM there is an appropriate EPO response to anaemia but even in the plateau phase the number of circulating BFU-E is reduced, reflecting a degree of marrow failure. However, the progenitors are normally sensitive to EPO in such patients, and therapeutic doses of EPO may correct the anaemia by a pharmacological rather than a physiological effect.

Anemia↗
PubMed1993

Recombinant factor VIIa for intracranial haemorrhage in a Jehovah's Witness with severe haemophilia A and factor VIII inhibitors.

A Jehovah's Witness with severe haemophilia A and a high titre, high responding inhibitor to both human and porcine factor VIII (FVIII) was treated with recombinant activated factor VII (rVIIa) during an episode of intracranial bleeding. He recovered completely without any adverse effects or neurological sequelae. Treatment with rVIIa in this case was safe and effective. This therapeutic agent should be considered in haemophilia patients with inhibitors who refuse management with blood products on religious grounds and when recombinant factor VIII is not a cost-effective option.

Adult↗
PubMed1993

Acquired haemophilia in association with type III von Willebrand's disease: successful treatment with high purity von Willebrand's factor and recombinant factor VIIa.

A patient with autosomal dominant (Type III) von Willebrand's disease (vWd) developed acquired haemophilia post-operatively, possibly due to exposure to amoxycillin. She refused porcine factor VIII (pFVIII) on religious grounds and was managed successfully with recombinant activated factor VII (rFVIIa) together with highly purified von Willebrand factor concentrate (vWf-VHP). In patients with acquired haemophilia rFVIIa appears to be a suitable agent for symptomatic management.

Factor VIIa↗
PubMed1992

Metabolically active antigen presenting cells are required for human T cell proliferation in response to the superantigen streptococcal M protein.

M protein from type 5 group A streptococci has been identified as a member of the family of polyclonal T cell activators termed superantigens because it preferentially stimulates T cells bearing specific V beta elements of the T cell receptor (TCR). In this study the molecular and cellular requirements for presentation of this protein to T cells were investigated. Only accessory cells (AC) expressing class II major histocompatibility complex (MHC) molecules were capable of supporting T cell activation in response to a 22 kDa fragment of M protein (pep M). Despite the need for class II elements, processing of pep M5 by the antigen-presenting cells (APC) was not required for T cell proliferation induced by pep M5. Fixation of APC by paraformaldehyde (PF) treatment impaired their ability to induce optimal T cell proliferation in response to pep M5 without significantly affecting interleukin (IL-2) production. In contrast, PF-fixation of cells from the B cell lymphoma line, Raji, did not affect their ability to present pep M5 to human T cells. Addition of rIL-1 and IL-6 to PF-treated APC restored pep M5-induced blastogenesis. Our data suggest that pep M5 directly associates with HLA class II molecules forming a complex that can induce IL-2 production but not optimal proliferation by T cells. Additional signals provided by the AC are required to trigger optimal T cell proliferation in response to this superantigen.

Antigen-Presenting Cells↗
PubMed1992

Cord compression: a rare complication of chronic lymphocytic leukaemia.

Two years after the diagnosis, while the disease was under good control, a patient with chronic lymphocytic leukaemia (CLL) developed spinal cord compression from an extradural solid tumour composed of leukaemic cells. He was treated successfully with resection of the tumour followed by local radiotherapy and systemic chemotherapy.

Acute Disease↗
PubMed1992

The value of the bone marrow plasma cell cytoplasmic light chain ratio in differentiating between multiple myeloma and monoclonal gammopathy of undetermined significance.

We compared the plasma cell light chain ratios in the bone marrows of 13 patients with multiple myeloma (MM), with those of 13 patients with monoclonal gammopathy of undetermined significance (MGUS). The mean light chain ratio in favour of the paraprotein isotype in the myeloma group was 51.83 (95% confidence limits (CL) 29.52-74.14), while in the MGUS group it was 5.30 (CL 2.07-8.52). The difference between the MGUS and MM groups was significant (p = 0.0005). Neither the bone marrow plasma cell count nor the paraprotein level were significantly correlated with the light chain ratio in either of these two groups. We found a cut-off ratio of 8 to be the most useful in differentiating between myeloma and MGUS. Only one patient with myeloma had a ratio below 8, and one MGUS patient had a ratio above this cut-off point. We conclude that determination of the bone marrow plasma cell light chain ratio is a simple and useful test in differentiating between myeloma and MGUS in difficult cases.

Aged↗
PubMed1992

Role of splenectomy in chronic lymphocytic leukaemia with massive splenomegaly and cytopenia.

Fourteen cases of chronic lymphocytic leukaemia (CLL) and massive splenomegaly associated with anaemia and/or thrombocytopenia (stage C) with or without mechanical distress underwent splenectomy. Eleven regressed to stage A and 2 to stage B. All 6 patients with mechanical distress were relieved of their symptoms. Among 13 patients with anaemia, haemoglobin (Hb) level was normalised in 3, improved in 8 and showed no change in 2 cases. Among 13 patients with thrombocytopenia, platelet count was normalised in 10, improved in 1 and was unchanged in 2 cases. Mean Hb level increased from 89 g/l to 125 g/l and mean platelet count from 77 x 10(9)/l to 241 x 10(9)/l (p < 0.001 for both). Duration of response lasted for a mean period of 42.1 (CI 20.8-63.5) months. Mean survival after splenectomy was 44.5 months (CI 21.2-67.7). There was no operative mortality but 4 patients had significant post-operative morbidity. It is concluded that splenectomy is beneficial in advanced cases of CLL with massive splenomegaly and cytopenia.

Anemia↗
PubMed1991

T cell receptor V gene usage by human T cells stimulated with the superantigen streptococcal M protein.

M proteins, the major virulence factor of group A streptococci, have been implicated in the pathogenesis of acute rheumatic fever (ARF) and other streptococcal related autoimmune diseases. A 22-kD fragment of M type 5 protein is a potent stimulant of human T cells and has recently been shown by our laboratory to belong to the newly designated family of superantigens. Using flow cytometry and the polymerase chain reaction, we demonstrate that this molecule reacts with subsets of human T cells expressing specific T cell receptor (TCR) V beta elements, namely V beta 2, 4, and 8. We employed similar techniques to analyze the TCR V alpha usage of pep M5-stimulated T cells. These studies revealed that the preferential usage of particular V alpha elements is not specific for the superantigen; rather, it may reflect the repertoire of the individual being tested. The expansion of a large number of T cells bearing specific TCR V beta sequences by M protein may account for its role in mediating the pathogenesis of post-streptococcal diseases. Furthermore, the preferential usage of TCR V alpha elements in certain individuals may be an important factor that predisposes them to development of self-reactivity.

Antigens, Bacterial↗
PubMed1991

Role of splenectomy as a salvage procedure in thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura is a rare but serious haematological disease for which first-line therapy is medical, but not always successful. The role of splenectomy in the management of such patients is unclear. This paper reports three patients with the condition who went into remission following splenectomy after other forms of therapy had failed. Because thrombotic thrombocytopenic purpura is nearly always fatal if a remission is not obtained, splenectomy should be considered in patients who prove to be resistant to medical therapy.

Adult↗
PubMed1991

Use of leucocyte alkaline phosphatase (LAP) score in differentiating malignant from benign paraproteinaemias.

The leucocyte alkaline phosphatase (LAP) score of peripheral blood neutrophils was examined in 20 patients with multiple myeloma and compared with the score in 18 patients with monoclonal gammopathy of undetermined significance (MGUS). The mean (95% confidence limit) LAP score in those with multiple myeloma was 186 (169-218) compared with 92 (64-120) in the MGUS group. In the multiple myeloma group all but one patient had a high LAP score, irrespective of disease. No cause for raised LAP, such as infection, was present in any of the patients with multiple myeloma. In the MGUS group six patients had a raised LAP score; in two of them another cause for such a rise was present (autoimmune haemolytic anaemia and primary thrombocythaemia). In neither group did the LAP score correlate with duration of the disease, bone marrow plasma cell count, paraprotein concentration, haemoglobin, total white cell or neutrophil count. It is concluded that a normal LAP count in patients with paraproteinaemia suggests a benign condition, but a raised count does not indicate a malignant condition.

Aged↗
PubMed1990

Accessory cell-independent stimulation of human T cells by streptococcal M protein superantigen.

Stimulation of T cells by superantigens has been reported to be dependent on the presence of APC where binding to class II molecules is a prerequisite to recognition by the TCR. We examined the response of human T cells and a leukemic T cell line, Jurkat to the superantigen, streptococcal M protein. We show that immobilized or cross-linked streptococcal M protein stimulates Jurkat cells (V beta 8), but not normal purified human T cells, to produce IL-2. Activation of purified T cells by this superantigen required costimulatory signals provided by PMA, IL-1, and IL-6. These cytokines and growth factors alone can induce IL-2 production by T cells; however, proliferation occurred only in the presence of superantigen, which together with PMA, IL-1, and IL-6 induced the expression of IL-2R alpha on T cells. Similar results were obtained when the response of purified T cells to another known superantigen, staphylococcal enterotoxin B were examined, indicating that this phenomenon is not unique to M protein. Superantigens interact with a large number of T cells with particular V beta, and thus provide excellent models for studies of the role of biochemical events and signal transduction in T cell activation. Understanding these events may also explain the pathogenesis of autoimmune diseases associated with certain superantigens, such as streptococcal M protein that is thought to be involved in rheumatic fever and rheumatic heart disease.

Antigen-Presenting Cells↗
PubMed1990

Superantigenicity of streptococcal M protein.

M proteins that define the serotypes of group A streptococci are powerful blastogens for human T lymphocytes. The mechanism by which they activate T cells was investigated and compared with the conventional T cell mitogen phytohemagglutinin, and the known superantigen staphylococcal enterotoxin B. Although major histocompatibility complex (MHC) class II molecules are required for presentation, there is no MHC restriction, since allogeneic class II molecules presented the bacterial protein to human T cells. Type 5 M protein appears to bind class II molecules on the antigen-presenting cells and stimulate T cells bearing V beta 8 sequences. Our results indicate that this streptococcal M protein is a superantigen and suggest a possible mechanism of its role in the pathogenesis of the postinfectious autoimmune sequelae.

Antibodies, Monoclonal↗