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Biomedical subjects

D A Isenberg

Publications and source records attributed to D A Isenberg.

At least 451 records · Page 25Linked to original sources
PubMed1981

Characterization of polymyositis infiltrates using monoclonal antibodies to human leucocyte antigens.

Frozen serial sections of muscle from 15 patients with polymyositis and three normal controls were studied by indirect immunofluorescence with a panel of mouse monoclonal antibodies to various human leucocyte components. The results showed good correlation with conventional histology. In addition, large numbers of T lymphocytes were identified in those cases with a marked inflammatory infiltrate. Many of the T cells probably bear HLA-DR antigen as the anti-HLA-DR antibody stained as many cells as the anti-leucocyte antiserum. This strongly suggests that the T cells present are 'activated'. In two patients HLA-DR-positive material was identified apparently diffusing from the infiltrates into muscle fibres suggesting its release as a soluble factor. In one case, structures with the appearance of giant cells were seen. The method promises to provide new information on the nature of infiltrating leucocytes which may provide more accurate diagnostic and prognostic information than conventional histology alone.

Adult↗
PubMed1980

Osteosarcoma complicating familial Paget's disease.

A most unusual family with aggressive Paget's disease is reported. Three brothers out of 10 siblings developed the disease at a relatively early age. Two of these brothers developed an osteosarcoma and died. It is emphasized that very little information is available concerning the predisposition to severe polyostotic disease and even sarcomatous change when Paget's disease begins at a young age or is familial. Possibly the risk of these serious complications is then greater than when the disease is sporadic and begins later in life.

Adult↗
PubMed1978

Neurological involvement in the epidermal naevus syndrome.

The case of a left handed girl aged 18 years suffering from the "epidermal maevus syndrome" is described. She presented with dysphasia, transient left hemiparesis, and sensory symptoms due to an occlusion of the right internal carotid artery. Arterial occlusion, abnormal retinal vessels, and Raynaud's phenomenon have not been previously documented. The neurological complications of this syndrome are discussed. It is suggested that the arterial occlusion may have been caused by a dysplastic artery.

Adolescent↗
PubMedDate not supplied

Functional and modelling studies of the binding of human monoclonal anti-DNA antibodies to DNA.

The relationships between the antigen-binding specificities of four human monoclonal anti-DNA antibodies and the structural aspects of the combining sites of two of these were examined. Competition ELISAs were used to examine the reactivities of two IgM MAbs (WRI-176 and RT-79) and two IgG mAbs (D5 and B3) to a wide range of polynucleotides. The mAbs WRI-176 and RT-79 were found to bind predominantly ssDNA, with a preference for poly (dT), whilst D5 and B3 bound components of both ss- and dsDNA, and Z-DNA. The mAb B3 also exhibited a preference for A(T) rich nucleotides. Computer models were generated for the Fv regions of WRI-176 and B3. Models for RT-79 and D5 were not generated as the structure of the long CDR-H3 loops in these mAbs could not be predicted. The B3 combining site contains a groove flanked by three arginines at positions CDR-L1-27A, CDR-L2-54 and CDR-H2-53. Using interactive molecular graphics, B-DNA was docked into the B3 antigen combining site along the plane of the VH/VL interface, whilst Z-DNA was best-fitted at approximately 90 degrees to this direction. The models provide a hypothesis to explain the ability of a single autoantibody to bind two different antigens. In addition, aspects of the base specificity of B3 may be explained. The model of the WRI-176 Fv region revealed a relatively flat surface, on which a large number of hydrophobic and aromatic residues were present. Trp-H52, in particular, is prominent on the surface. This may participate in ssDNA binding through base stacking interactions. The models allow identification of potential targets for site-directed mutagenesis.

Amino Acid Sequence↗
PubMedDate not supplied

Detection of anticardiolipin antibodies in culture supernatants.

OBJECTIVE: We have attempted to devise a method for measuring the levels of anticardiolipin antibodies produced in in vitro culture of peripheral blood mononuclear cells isolated from patients with systemic lupus erythematosus (SLE), with or without circulating anticardiolipin antibodies, patients with the primary antiphospholipid syndrome (PAPS) and normal controls. METHODS: Peripheral blood mononuclear cells were isolated and cultured for up to six days, in the presence or absence of added cytokines in the culture medium. Supernatants harvested after culture were tested by ELISA for the presence of anticardiolipin antibodies. RESULTS AND CONCLUSION: Despite variation of the culture conditions and of the cell numbers and populations used, it was found that accurately measurable levels of anticardiolipin antibodies could not be detected reliably in any of the culture supernatants. It is concluded that alternative methods of measurement of antibody production need to be explored.

Antibodies, Anticardiolipin↗
PubMedDate not supplied

Concurrence of sarcoidosis and systemic lupus erythematosus in three patients.

We present three cases of patients with systemic lupus erythematosus and sarcoidosis. Although both of these conditions are thought to involve autoimmune mechanisms they occur together only rarely. Our cases suggest that their concurrence may be more common than previously thought, and raise issues regarding the management of patients with SLE. We discuss the possibility that these two diseases are either causally or mechanistically related.

Adult↗
PubMedDate not supplied

Disease activity in systemic lupus erythematosus: report of the Consensus Study Group of the European Workshop for Rheumatology Research. I. A descriptive analysis of 704 European lupus patients. European Consensus Study Group for Disease Activity in SLE.

Using a detailed questionnaire, the cumulative historical and current demographic, clinical and serological data on 704 SLE patients from 29 European centres and 14 countries have been assessed. Ninety-three percent of the patients were Caucasian and the female/male ratio was 10:1. Analysis of the cumulative incidence showed that arthralgia/arthritis (94%), rash (69%), Raynaud's phenomenon (49%), serositis (44%) and renal disease (38%) were the most frequent clinical manifestations. Virtually all the patients (98%) were antinuclear antibody positive, while anti-ds-DNA antibodies (76%), hypocomplementaemia (71%) and anti-Ro(SSA) antibodies (35%) were frequent serological abnormalities. Whilst much of this data is in line with previous reports, it is notable that renal, lung, and central nervous system involvement and the frequency of rheumatoid factor, anti-Sm and anti-RNP antibodies were much lower than in most comparable series in the United States. We assume that ethnic differences and the greater present awareness of lupus could explain this variations. Low dose corticosteroids, non-steroidal anti-inflammatory drugs and anti-malarials were used to treat over half of the patients, 75% of whom were between 15 and 55 years of age. This report offers a useful overview of lupus both clinically and serologically in Europe in the 1990's.

Adolescent↗
PubMedDate not supplied

Disease activity in systemic lupus erythematosus: report of the Consensus Study Group of the European Workshop for Rheumatology Research. II. Identification of the variables indicative of disease activity and their use in the development of an activity score. The European Consensus Study Group for Disease Activity in SLE.

A European Consensus Group study, involving 29 centres from 14 countries, was performed in order to reach agreement on the definition of disease activity in systemic lupus erythematosus (SLE) and to construct a new disease index. Data on 704 lupus patients were collected and analysed, using univariate and multivariate statistical procedures, to select those clinical and laboratory features of the disorder which best correlate with the global assessment of disease activity assigned to the patients by the physician of each participating centre. A combination of 15 clinical and laboratory variables was shown to be the best predictor of disease activity in SLE. A European Consensus Lupus Activity Measurement (ECLAM) was then formulated. This index included the 15 selected variables, weighted (with some adjustments) according to their respective regression coefficients in the multivariate model. ECLAM appears to be an effective instrument for scoring patients with different degrees of disease activity. This is the first SLE disease activity index based on data from a very large number of lupus patients followed at a large number of lupus centres in different countries. It might therefore very well serve as a standardised measure for future European clinical studies. Final assessment of the validity, reliability and sensitivity of this index is now underway.

Europe↗
PubMedDate not supplied

Disease activity in systemic lupus erythematosus: report of the Consensus Study Group of the European Workshop for Rheumatology Research. III. Development of a computerised clinical chart and its application to the comparison of different indices of disease activity. The European Consensus Study Group for Disease Activity in SLE.

In the first phase of this study, a data-base containing clinical and laboratory findings of 704 patients with systemic lupus erythematosus (SLE), originating from 29 centres and 14 countries, was used to assess the validity of 4 common indices of disease activity, SLAM, BILAG, SLEDAI and SIS. The physician's judgement of activity was assumed as the unique reference criterion (gold standard). Computer programmes were developed to calculate automatically the 4 activity indices; this computation appeared to correspond with manual computations in a sample of 60 appropriately selected cases. All 4 indices were closely correlated with each other (r in the range of 0.716 to 0.872), and with the physician's score (r in the range of 0.620 to 0.719). In the second phase of the study the activity index developed in part I (ECLAM) was prospectively validated, and its performance compared to that of the other scales, both as a single state index and as a transition index (i.e., its ability to assess disease activity at a single point in time and to detect variations in consecutive readings). A computer-assisted clinical chart was prepared for this purpose. This chart allowed us to calculate automatically all the indices. Two consecutive observation times (time 0, and time 1 three months later) were included in the study protocol. Data on 75 patients from 19 centres were collected, and each patient was observed twice. All the computed indices were closely correlated, both at time 0 (r ranging from 0.725 to 0.884), and at time 1 (r ranging from 0.607 to 0.833).(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnosis, Computer-Assisted↗
PubMedDate not supplied

Anti-Rnp antibodies in chronic liver diseases.

Antinuclear antibodies are commonly observed in chronic liver disorders. Sera from 87 patients with various chronic liver diseases were tested for the presence of antibodies against two extractable nuclear antigens (ENA) - RNP and Sm. Using an enzyme-linked immunosorbent assay (ELISA) anti-RNP antibodies were detected in 13 patients (15%) most of whom had cryptogenic or primary biliary cirrhosis. When the sera were further tested by ELISA for the presence of anti-Sm antibodies no antibody binding could be detected. These findings support the notion that anti-RNP (but not anti-Sm) antibodies are included among the autoantibodies shared by systemic lupus erythematosus and chronic liver diseases.

Autoantibodies↗
PubMedDate not supplied

C-reactive protein in sera from patients with systemic lupus erythematosus.

One hundred and ninety sera from 27 patients with systemic lupus erythematosus (SLE) were tested by radial immunodiffusion for C-reactive protein (CRP). One hundred and fourteen (60%) of these samples from 22 patients had detectable CRP. There was a statistically significant association between clinical activity and serum concentration of CRP in the patients who consistently recorded elevated levels. CRP was not found to distinguish between disease activity and coincident infection in 2 patients whose SLE was complicated by tuberculosis.

Adult↗