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Biomedical subjects

A I Grayzel

Publications and source records attributed to A I Grayzel.

At least 19 recordsLinked to original sources
PubMed1989

Effect of long-term normalization of serum complement levels on the course of lupus nephritis.

PURPOSE: We compared the long-term outcome of patients with lupus nephritis in whom normalization of complement levels (CH50) was sustained by adjustment of immunosuppressive therapy to those patients with persistently low complement levels despite similar immunosuppression in whom therapy was adjusted solely on the basis of clinical disease activity. PATIENTS AND METHODS: Thirty-nine female patients with lupus nephritis recruited from 1972 to 1979 were prospectively studied (mean follow-up, 116.7 +/- 11 months). Entry criteria included initial renal biopsy, low CH50, and elevated anti-DNA antibody levels. A second biopsy was performed in 24 patients after an interval of 40.6 +/- 5 months. Treatment was started with prednisone (1 mg/kg/day). Azathioprine at a dose of 1.5 to 2.0 mg/kg/day was added if complement was not normalized by prednisone alone. Twenty-five of 39 patients had normal complement levels within six months (Group 1), and immunosuppressive therapy was tapered but continuously readjusted to the lowest dosage that preserved normal CH50 and maintained clinical remission. Eight of these 25 patients subsequently became persistently hypocomplementemic due to inadequate drug intake (Group 1B), whereas the complement levels continued to be controlled in the other 17 patients (Group 1A). Despite similar therapy, the remaining 14 patients did not achieve normalization of complement within the initial six months of therapy, and therefore future treatment decisions were based solely on clinical symptoms (Group 2). Renal pathologic lesions were classified according to World Health Organization criteria and a semi-quantitative chronicity index. RESULTS: During the first six months, there were no significant differences in clinical or histologic features between patients in whom complement levels were controlled and patients in whom complement levels were not controlled. After a mean observation period of 10 years, however, patients with consistent normalization of complement (Group 1A) did much better than patients with only short-term complement control (Group 1B) or persistent hypocomplementemia (Group 2). Both groups with low complement levels had a similar outcome with significantly worse kidney and patient survival. Life-table analysis demonstrated that the differences in outcome between complement-controlled and complement-uncontrolled groups became apparent only after five or more years of follow-up. Patients with a low chronicity score on initial biopsy whose complement level was controlled did uniformly well with no renal failure or death. (ABSTRACT TRUNCATED AT 400 WORDS)

Azathioprine↗
PubMed1987

Suppression of anti-DNA antibody synthesis in vitro by a cross-reactive antiidiotypic antibody.

An understanding of the regulatory mechanisms that govern the humoral immune response will be facilitated by the availability of techniques for the measurement of specific antibody production in vitro. We have developed an enzyme-linked immunosorbent assay system for the measurement of in vitro anti-DNA antibody production by peripheral blood mononuclear cells (PBMC) from patients with systemic lupus erythematosus. Using this technique, the PBMC from 74% of serologically active SLE patients produced levels of anti-DNA antibodies that were greater than 2 SD above the mean of 18 +/- 9 IU/ml for normal subjects. Furthermore, the addition of 3I, a monoclonal anti-idiotypic antibody that recognizes a cross-reactive determinant on anti-DNA antibodies, was shown to specifically inhibit anti-DNA production in vitro.

Antibodies, Anti-Idiotypic↗
PubMed1985

The effect of serum from patients with systemic lupus erythematosus on the immune response of normal lymphocytes.

In contrast to influences that act to reduce the function of suppressor T cells, we describe a factor found in the sera of 13/28 patients with systemic lupus erythematosus (SLE) that augments the response of normal donor peripheral blood lymphocytes to stimulation by pokeweed mitogen (PWM) in vitro. This factor was present in 1/2 of our patients with active SLE, but not in normal blood donors; it required the presence of pooled AB serum in the culture medium; was specific for stimulation by PWM and not by phytohemagglutinin, concanavalin A or purified protein derivative; it appeared to act predominantly on B lymphocytes and was neither immunoglobulin nor interferon. This augmentation was seen to a lesser degree with rheumatoid sera, but not with psoriatic arthritis sera or sera of SLE patients on dialysis.

Arthritis, Rheumatoid↗
PubMed1984

Persistence of pneumococcal antibodies after immunization in patients with systemic lupus erythematosus.

Antibody levels to 12 different pneumococcal capsular polysaccharides as well as the combined mean antibody level were measured in 19 patients with systemic lupus erythematosus (SLE) at 1, 2 and 3 years after immunization with a polyvalent pneumococcal vaccine and compared to 5 normal control subjects immunized at the same time. The mean levels in the 19 SLE patients were lower in all 3 years but the difference reached significance only in Year 1. At 3 years, 8 of the 19 SLE patients had levels below that considered to be protective and one such patient developed a pneumococcal pneumonia.

Antibodies, Bacterial↗
PubMed1982

Natural killer cell activity of mononuclear cells from rheumatoid patients measured by a conjugate-binding cytotoxicity assay.

The natural killer cell activity of synovial fluid mononuclear cells and synovial membrane mononuclear cells from patients with rheumatoid arthritis was compared with that of paired peripheral blood mononuclear cells from many of these patients. Natural killer cell activity was measured by the use of a conjugate-binding cytotoxicity assay with an erythroleukemic cell line, K562, as target. There was no significant difference when 15-minute target binding by peripheral blood mononuclear cells was compared with synovial fluid mononuclear cells. Target binding of synovial greater (P less than 0.05) than that of peripheral blood cells. Three-hour target killing, however, was significantly greater when synovial fluid mononuclear cells were compared with the peripheral blood cells, P less than 0.01, and when synovial membrane cells were compared with the peripheral blood cells (P less than 0.05). The products of binding and 3-hour killing, a reflection of the total number of mononuclear cells participating in cytotoxicity, were significantly greater when either synovial fluid or synovial membrane mononuclear cells were compared with peripheral blood mononuclear cells (both P less than 0.01). Electron microscopy confirmed the presence of large granular lymphocytes, representing 20% of the peripheral blood cells and 37% of the synovial fluid mononuclear cells. Interferons were detected in 10/12 rheumatoid and 3/12 nonrheumatoid synovial fluid samples studied. These findings indicate that functional natural killer cells are selectively increased in the rheumatoid joint and may contribute to the overall increase in immunologic activity found in the joints of these patients.

Arthritis, Rheumatoid↗
PubMed1982

Psychologically distinguishable groups of rheumatoid arthritis patients: a controlled, single blind study.

Systematic measures of mood and psychological symptoms were obtained for 68 ambulatory arthritis patients on two standard questionnaires, the Brief Symptom Inventory (BSI) and the Profile of Mood States (POMS). We studied two groups of rheumatoid arthritis patients, one positive and the other negative for rheumatoid factor and erosive joint changes. A third group of patients had other forms of arthritis. All were matched for chronicity and functional impairment as well as psychosocial background variables. We found a distinct psychometric response profile that allowed us to sort patients into the three clinical groups with an accuracy ranging from 63% to 100%.

Adult↗
PubMed1982

Endogenous and interferon-augmented natural killer cell activity of human peripheral blood mononuclear cells in vitro. Studies of patients with multiple sclerosis, systemic lupus erythematosus or rheumatoid arthritis.

Peripheral blood mononuclear cells (PBMC) of normal human donors are spontaneously cytotoxic for certain tumour-derived and virus-infected target cells. This so-called natural killing (NK) can be augmented by the action of interferons (IFN) and by IFN-inducers. In this study, we have compared both endogenous and augmented NK activity of normal donors with that of patients suffering from either multiple sclerosis (MS), systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA). Endogenous NK was assayed using an NK susceptible target cell (K562), and augmented NK using a target cell (WI-L2) which is lysed only by NK effector cells that have been pre-stimulated by IFN or IFN-inducers. While NK function appeared normal in RA patients, this study confirms previous reports of defective endogenous NK in many MS and SLE patients. In addition, anomalous IFN-augmented NK was also detected in many patients with these two diseases, indicating that defective NK function cannot always be corrected by IFN treatment in vitro. Analysis of IFN production, endogenous NK and IFN-augmented NK by individual patients with MS or SLE showed the defects in their IFN-NK systems to be highly selective, suggesting that individual components of this system may operate independently.

Adult↗
PubMed1981

The effect of continuous normalization of serum hemolytic complement on the course of lupus nephritis: a five year prospective study.

We have completed a five year prospective study of the effect of continuous normalization of serum hemolytic complement (CH50) in 25 patients with lupus nephritis. At the end of five years 22 patients were being actively followed; 13 in a CH50 controlled group and nine in a CH50 uncontrolled group. Serial renal biopsy specimens were obtained from 19 patients. The results demonstrate a trend toward stabilization of renal histology, creatinine clearance and serum creatinine at a lower final mean dose of prednisone in the complement controlled group.

Antibodies↗
PubMed1981

Interferon production of vitro by leucocytes from patients with systemic lupus erythematosus and rheumatoid arthritis.

The production of interferons (IFN) by peripheral blood leucocytes from normal donors an patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) has been investigated in response to several IFN inducers in vitro. Whereas IFN responses of RA donors did not differ significantly from the normal group, those of SLE patients were significantly reduced, and many of these patients failed to respond to all. Patients with active or acute SLE responded significantly less well than those with inactive disease. There was no apparent effect of steroid therapy on the IFN responses of either SLE or RA patients. These data may indicate a basic immunological defect of the circulating leucocytes of SLE patients, which may be responsible for some of the in vitro lymphocyte anomalies reported for this disease.

Adult↗
PubMed1980

Impaired response to pneumococcal vaccine in systemic lupus erythematosus.

An immunization program with pneumococcal vaccine was carried out in 38 patients with systemic lupus erythematosus (SLE). Mean antibody levels at 1 month and 1 year were significantly lower than in normal controls. This decreased response did not correlate with drug therapy at the time of immunization. Other parameters such as anergy state, renal function, and serum immunoglobulin levels also did not correlate with antibody response. There were no adverse effects noted in the vaccinated group in comparison to matched non-vaccinated SLE patients.

Adult↗