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Biomedical subjects

A M Denman

Publications and source records attributed to A M Denman.

At least 37 records · Page 2Linked to original sources
PubMed1991

Cytokine-independent progression of immunoglobulin production in vitro by B lymphocytes from patients with systemic lupus erythematosus.

B lymphocytes from patients with systemic lupus erythematosus (SLE) secreted high levels of immunoglobulin spontaneously when cultured in vitro. Addition of the cytokines interleukin-2, interleukin-4 and interleukin-6 either alone or in combination failed to augment spontaneous immunoglobulin synthesis. Percoll-separated low-density SLE B lymphocytes matured into immunoglobulin-secreting cells also independent of exogenous interleukins. During maturation these cells became enlarged and less dense, and began to express CD23. This was in contrast to normal B cells, which did not secrete immunoglobulin spontaneously but synthesized IgM after interleukin stimulation. These results indicate that in vitro immunoglobulin synthesis by SLE B cells is already initiated in these cells and progresses independently of further stimulatory manoeuvres.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1989

Endothelial prostacyclin release in systemic lupus erythematosus.

The ability of sera from patients with SLE to stimulate endothelial cell prostacyclin production was studied using a standardized assay system for testing the effects of serum on cultured human endothelial cell monolayers. The effects of 20 normal and 32 SLE sera on endothelial prostacyclin production were measured. No differences between the rates of prostacyclin production were seen between the two groups, either basally or when prostacyclin release was stimulated with thrombin or bradykinin. In the SLE samples there was no correlation between anticardiolipin IgG or IgM titres and their ability to stimulate basal or agonist-induced prostacyclin release. These results suggest that the elevated risk of thrombosis in SLE patients is not associated with inhibition of endothelial cell prostacyclin synthesis.

Adolescent↗
PubMed1989

Herpes simplex virus and the rheumatic diseases.

A viral aetiology for rheumatoid arthritis and inflammatory connective tissue diseases has been sought in general terms first, by studying viral growth patterns in lymphocytes from the blood and lesions of patients affected second, by analysing lymphocyte concentrations of the interferon-induced enzyme 2-5 oligo-adenylate synthetase (2-5 A); and third, by probing Southern blots of lymphocyte DNA with viral probes. Indirect evidence consistent with a viral aetiology has been found in several such diseases, but direct proof has been difficult to adduce. There is some suggestion that herpes simplex viral (HSV) DNA is present in Behcet's blood lymphocytes, but the findings are inconsistent. It is also plausible that viruses such as HSV do not induce these diseases through classic immunopathological mechanisms, but as "promoters" of abnormal lymphoproliferation in individuals with predisposing defects, possibly related to selective DNA repair defects.

Behcet Syndrome↗
PubMed1989

Thrombophlebitis migrans following co-trimoxazole therapy.

We report an unusual and severe vasculitic disorder following co-trimoxazole, given orally for a urinary tract infection. The vasculitis was manifest solely as thrombophlebitis migrans and involving only veins without evidence of polyarteritis nodosa, or underlying malignancy.

Anti-Infective Agents, Urinary↗
PubMed1988

Use of T cell cloning to detect in vivo mutations induced by cyclophosphamide.

By cloning T cells, mutations at the hypoxanthine-guanine phosphoribosyltransferase locus were quantified in peripheral blood lymphocytes of 12 patients with connective tissue diseases receiving long-term cyclophosphamide. Frequency of mutation was higher than in control subjects and was related to the duration of therapy; therefore, some cells with mutations are long-lived, and these cells accumulate in the peripheral circulation. Mutation frequency was also independently related to age. The results indicate that even low doses of cyclophosphamide are mutagenic and may explain, in part, why these patients are at risk of drug-induced malignancy.

Chromosome Mapping↗
PubMed1988

Treatment with acyclovir does not affect orogenital ulcers in Behçet's syndrome: a randomized double-blind trial.

Acyclovir is a potent antiviral drug, of proven efficacy in the treatment of herpes simplex virus infection. Since this virus has been implicated in the aetiology of Behçet's syndrome, the effect of acyclovir on orogenital ulceration in this condition was determined in a randomized, double-blind, placebo-controlled, crossover trial. Eighteen of 22 patients entering the study completed the trial. Treatment with acyclovir failed to alleviate the frequency and severity of orogenital ulceration or other disease features.

Adolescent↗
PubMed1988

A search for retrovirus infection in systemic lupus erythematosus and rheumatoid arthritis.

Evidence for retroviral infection in general and human immunodeficiency virus (HIV) infection in particular was sought in freshly isolated peripheral blood T cells, B cells, and monocyte-macrophages from patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) and also in T cell and B cell lines established from the same source. Similar cells isolated from rheumatoid synovial membrane were also examined. The strategy used for the detection of virus was cocultivation with susceptible cell lines looking for syncytia formation, reverse transcriptase production, and nucleic acid hybridisation with HIV cDNA probes. No evidence for infection was obtained.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Increased sensitivity of lymphocytes from patients with systemic autoimmune diseases to DNA alkylation by the methylating carcinogen N-methyl-N-nitrosourea.

Lymphocytes from patients with various diseases associated with autoimmunity showed both impaired capacity to repair O6-methylguanine (a powerful, promutagenic, directly miscoding base lesion) and increased sensitivity to the cytocidal effects of cellular methylation by N-methyl-N-nitrosourea (MNU) compared with normal controls and patients with other disorders. Defective repair of O6-methylguanine was significantly associated with arthritis and myositis in the group with systemic lupus erythematosus (SLE), and increased sensitivity to the toxic action of MNU was associated with the presence of immune complexes and the administration of steroids to patients with Behçet's syndrome. The results indicate that lymphocytes from patients with the autoimmune diseases studied are more susceptible to DNA damage with possible relevance to aetiopathogenesis.

Adult↗
PubMed1987

Sister-chromatid exchange frequencies in fibroblasts and lymphocytes of patients with systemic lupus erythematosus.

Sister-chromatid exchange (SCE) frequencies have been measured in lymphocytes and fibroblasts of patients with systemic lupus erythematous (SLE) and healthy controls, and in lymphocytes of control patients with serum anti-nuclear antibodies (ANA) but no other disease manifestations of SLE. The SCEs of SLE lymphocytes were higher than those of the controls but the SCEs of the SLE fibroblasts did not differ from those of the controls. The SCEs of the controls with positive ANA did not differ significantly from those of the healthy controls. There was no correlation between SCE frequencies of the SLE lymphocytes and disease activity determined by many clinical and laboratory measurements. Primary and secondary DNA-repair defects in SLE cells are considered.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1987

Cyclosporin A in the treatment of severe Behçet's uveitis.

Twelve patients with active Behçet's uveitis with marked deterioration of visual acuity in at least one eye were treated with cyclosporin A (CyA). An initial improvement in the severity of ocular inflammation and systemic features occurred in all cases and persisted until the dose was reduced or the drug withdrawn when a rapid recurrence of symptoms was noted. The visual acuity also initially improved in ten patients and this was maintained in seven cases until the dose of CyA was reduced. At this time, acuity was unchanged in two patients and was worse in three others-two of the latter as a result of vitreous haemorrhage in the absence of active inflammation. Seven of the 12 patients had therapy stopped because of complications; severe malaise and nausea (three cases), decreased renal function (three cases), and blindness (one case). Cyclosporin A is of value in the control of Behçet's uveitis but toxicity limits its use and the benefits only last while the patient is on this therapy.

Adult↗
PubMed1987

Sensitivity of lymphocytes from patients with systemic lupus erythematosus to the induction of sister chromatid exchanges by alkylating agents and bromodeoxyuridine.

Several authors have suggested that the cells of patients with systemic lupus erythematosus (SLE) have defects of DNA repair. Cells from patients with the classical chromosomal instability syndromes, thought to be due to defects in DNA repair, are hypersensitive to the chromosome damaging effects of some DNA damaging agents, measured as sister chromatid exchange (SCE). We have observed that lymphocytes of patients with SLE are not more sensitive than lymphocytes from healthy individuals to the SCE inducing effects of the DNA damaging agents methyl nitrosourea, methyl methanesulphonate, chlorambucil, and bromodeoxyuridine. These observations do not support the suggestion that cells of patients with SLE have an underlying defect of DNA repair.

Alkylating Agents↗
PubMed1987

Spontaneous production of B cell growth factors by SLE lymphocytes.

Systemic lupus erythematosus blood lymphocytes produce B cell growth factors (BCGF) spontaneously to an extent comparable with pokeweed mitogen-stimulated lymphocytes from normal donors. BCGF production by SLE lymphocytes is not increased by PWM and these cells are refractory to exogenous BCGF. Production requires B cells and irradiated T cells but not accessory cells. The properties of spontaneously synthesized BCGF differ in some respects from those induced by PWM. These findings suggest that the abnormal B cell proliferation characteristic of SLE may result, at least in part, from autostimulatory growth factors.

Growth Substances↗
PubMed1987

Lymphokine-activated killer cell activity in rheumatoid arthritis.

The lymphokine-activated killer (LAK) cell activity in the peripheral blood of 23 patients with rheumatoid arthritis has been studied. Two control groups comprised (a) nine patients with another chronic inflammatory disease (sarcoidosis) and (b) 19 normal healthy volunteers. The LAK activity induced by human recombinant IL-2 was very similar in controls and patients with rheumatoid arthritis but was significantly decreased in patients with sarcoidosis, although the frequency of LAK-cell precursors measured using a limiting dilution assay was comparable in all three groups. The DNA synthetic response of peripheral blood mononuclear (PBM) cells to IL-2 was slightly decreased in patients with both rheumatoid arthritis and sarcoidosis as compared to controls, but this decrease was not statistically significant. Spontaneous DNA synthesis in PBM cells cultured in the absence of IL-2 was essentially identical in all three groups. We conclude on the basis of these results that the higher risk of non-Hodgkin's lymphomas in patients with rheumatoid arthritis cannot be attributed to an impairment of LAK activity. Furthermore, the doses of gamma-irradiation, which abolished the 'background' cytotoxicity of PBM cells cultured without IL-2 and also blocked effectively both spontaneous and exogenous IL-2-dependent DNA synthesis, had little effect on the generation of LAK activity. These observations are discussed in regard to the role of non-specific cytotoxic cells and the therapeutic efficacy of antiproliferative drugs in rheumatoid arthritis.

Adult↗