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Biomedical subjects

A M Denman

Publications and source records attributed to A M Denman.

At least 73 records · Page 4Linked to original sources

Anticardiolipin antibodies: occurrence in Behçet's syndrome.

Anticardiolipin antibodies have recently been described in association with arterial and venous thrombosis, and with neurological symptoms, in connective tissue diseases. In a study of 70 patients with Behçet's syndrome 13 patients had these antibodies. Of these 13 patients eight had a history of either retinal vascular pathology, cerebral infarction, or thrombophlebitis. The association of retinal vascular disease and the presence of anticardiolipin antibodies was statistically significant.

Antibodies↗

Interferon-gamma production by peripheral blood mononuclear cells from patients with Behçet's syndrome.

Interferon-gamma (IFN-gamma) production by peripheral blood mononuclear cells (MNC) from patients with Behçet's syndrome was compared with production by MNC from control donors. There was no evidence of significant spontaneous production of either IFN-gamma or interferon-alpha (IFN-alpha) by unstimulated MNC from patients or controls but phytohaemagglutinin treatment of MNC induced IFN-gamma in both patient and control groups. Significantly higher titres of IFN-gamma were produced by MNC from patients with Behçet's syndrome than MNC from patients with other inflammatory diseases (P = 0.005), hospital controls (P = 0.036) or healthy controls (P = 0.009). No IFN was detected in plasma from patients or controls.

Adolescent↗

Effects of immunosuppression on herpes simplex virus growth in lymphocytes of patients with connective tissue diseases.

The growth of herpes simplex virus (HSV) was measured in blood lymphocytes isolated from patients with connective tissue diseases receiving immunosuppressive drugs. Whereas lymphocytes from such patients were frequently nonpermissive for HSV before treatment, they became permissive in most patients after treatment. The exception was the persistence of nonpermissiveness in lymphocytes of treated patients whose disease was associated with malignant disease.

Adult↗

Interferon system in patients with systemic juvenile chronic arthritis: in vivo and in vitro studies.

Eighteen patients with active systemic juvenile chronic arthritis (JCA) were studied for periods of up to 1 year to see whether any relationships existed between the interferon (IFN) response, the course of the underlying disease and intercurrent infections. The control group consisted of 23 children who were each seen on one occasion. IFN-alpha production by mononuclear cells (MNC) cultured in vitro was stimulated with Newcastle disease virus (NDV). Comparison of the mean IFN-alpha responses from all patients with control responses showed that MNC from the JCA group produced significantly more IFN-alpha. Furthermore, MNC obtained from JCA patients at times of systemic flare produced significantly higher titres of IFN-alpha than at times when the patients were clinically stable. IFN-alpha production by MNC from individual patients fluctuated considerably from occasion to occasion whereas IFN-gamma production by MNC induced with phytohaemagglutinin (PHA) remained more stable. There was no significant difference between patients and controls with respect to IFN-gamma responses and no relationship with clinical condition. Serum IFN was not detected either by sensitive bioassays for IFN-alpha and IFN-gamma or by an immunoradiometric assay for IFN-alpha.

Adolescent↗

Joint complaints and food allergic disorders.

An important problem in investigating food allergic diseases is to adduce evidence that specific diseases of unknown cause may be attributable to food allergy. Polyarthritis is a good example of the difficulties involved in such studies because it is a very heterogeneous disorder and generalizations about aetiology are unlikely to prove correct. We have observed transient synovitis in both children and adults which is caused by food allergy. On the other hand we have not been able to show that food allergy demonstrably contributes to juvenile chronic arthritis or to rheumatoid arthritis in adults. The arthritis associated with inflammatory bowel disease undoubtedly responds to elemental diets and the mechanism of this remission warrants further investigation.

Arthritis, Rheumatoid↗

Defective repair of 0(6)-methylguanine in autoimmune diseases.

On the premise that somatic mutations may be involved in the pathogenesis of diseases such as systemic lupus erythematosus and rheumatoid arthritis, the proficiency of repair of 0(6)-methylguanine, a powerful, premutagenic, directly miscoding base lesion, was examined in the DNA of peripheral-blood mononuclear cells (mainly lymphocytes) from patients with such diseases. The capacity of lymphocytes to repair this lesion was impaired in many patients with autoimmune disease. In some healthy controls repair was also defective whereas in other, nonautoimmune diseases, it was not. These findings support the hypothesis that this defect of repair was not simply a result of the disease state. It is therefore postulated that defective repair of 0(6)-methylguanine could be one of the factors determining the susceptibility of autoimmune diseases in genetically predisposed individuals.

Arthritis, Rheumatoid↗

Intensive immunosuppression versus prednisolone in the treatment of connective tissue diseases.

Intensive immunosuppression (IIS) was compared with prednisolone alone over a 2-year period in the treatment of severe connective tissue diseases. IIS consisted of 15 daily infusions of 750 mg antilymphocyte globulin (ALG), azathioprine 2.5 mg/kg/day, and prednisolone reducing from 150 mg, followed by maintenance azathioprine and prednisolone. The initial dose for prednisolone by itself was 60 mg and patients not responding to this regimen over a minimum of one month were then given IIS. Forty-one patients with life-threatening or severely disabling polyarteritis nodosa (PAN), dermatomyositis/polymyositis (DM), or systemic lupus erythematosus received one or other treatment. All 11 patients who received IIS for PAN remitted. Ten of these had renal impairment which was reversed or halted with IIS, and in 6 of these renal function had been deteriorating with prednisolone alone. One patient died of pneumonia in renal failure 9 months later but with PAN in remission. Two further patients, neither having renal involvement, achieved remission with prednisolone alone. Early cytotoxic treatment would seem to be indicated in PAN when there is renal involvement. Two patients with DM entered remission or prednisolone alone. The remaining 12, of whom 5 had failed steroid therapy, received IIS. Improvement or halting of deterioration was achieved in all 12 with best results in those without marked muscle wasting consequent to disease of long duration. The results suggest that IIS may be a useful adjunct in those patients failing to respond to prednisolone. IIS seemed no more effective than prednisolone alone in the treatment of the 14 patients with SLE and in particular lupus nephritis. Flares in disease activity were common in both groups and appeared to be related to prednisolone dosage. IIS was generally well tolerated, though infection occurred in 2 patients. Vertebral collapse or osteonecrosis of the femoral head occurred in 3 patients following IIS, all of whom had been previously receiving prednisolone for long periods.

Adolescent↗

Immunosuppression and the rheumatic diseases.

Ignorance of the basic nature of rheumatoid arthritis precludes the introduction of rational schemes for using cytotoxic drugs. It is still plausible that the autoimmune and other immunological abnormalities which accompany this disease are the secondary effects of persistent antigen, for example, related to microbial infections. In this event, cytotoxic drugs may diminish the inflammatory response but their effects on immune responses would be irrelevant or even undesirable. Should rheumatoid arthritis prove to be a primary immunoproliferative disorder, cytotoxic drugs may prove to be of value not because of their conventional immunosuppressive effects but because of their selective action on the proliferating cells. Indeed, current evidence suggests that these drugs enhance rather than depress conventional immune responses, at least in the doses given to patients with rheumatic disorders.

Adolescent↗

Virus infections and chronic rheumatic disorders.

There is little direct evidence that viruses cause inflammatory arthritis in the sense that infectious agents classically cause disease. However, there are several mechanisms by which virus infections could be implicated in the pathogenesis of such disorders. In particular virus infection of lymphocytes could produce the combination of selective immunodeficiency and immune stimulation that characterizes many rheumatic disorders. In addition re-combination events between integrated pro-viruses in DNA and exogenous infections would account for the lack of any obvious correlation between the appearance of these disorders and any obvious preceding viral infection. Certainly, more sophisticated approaches will be needed to test such hypotheses rather than relying on classical techniques for viral isolation.

Antigens, Viral↗

Selective immunosuppressive effects of measles virus infection.

The antibody response to diphtheria toxoid by cultured tonsil cells was suppressed by measles virus, which productively infected a small percentage of both T and B lymphocytes. However, infection of cultures spontaneously secreting antibody and immunoglobulin (with Herpes simplex virus) or measles virus did not result in immunosuppression. Immunosuppression by measles virus may thus be attributed to a selective effect on the inductive phase of the response and suggest that infection of immunoglobulin-producing B lymphocytes does not alter the ability of these cells to secrete antibody.

Adolescent↗

Defective B cell function in systemic lupus erythematosus.

The in vitro synthesis of specific anti-influenza virus antibody was measured in cultures of peripheral blood lymphocytes from 25 patients with systemic lupus erythematosus (SLE) and 23 control subjects. Whilst all cultures derived from normal individuals synthesized specific antibody, cultures from patients with SLE were consistently unable to produce anti-influenza antibody. This defect could not be corrected by manipulating the culture conditions or by in vivo immunization. Co-cultivation of separated SLE-B or control B cells, with SLE-T or control T cells showed that the immunodeficiency exhibited by the SLE peripheral blood lymphocytes resides in the B cells.

Antibodies, Viral↗