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Biomedical subjects

R M Bernstein

Publications and source records attributed to R M Bernstein.

At least 91 records · Page 5Linked to original sources
PubMed1990

Selective polyclonal increase of immunoglobulin G1 subclass: a link with Sjögren's syndrome.

A selective polyclonal increase in IgG1 has been described previously in a group of patients with connective tissue disease; nine of the 16 patients had a prior diagnosis of systemic lupus erythematosus (SLE). A detailed clinical and serological study of 32 patients with this immunoglobulin abnormality has now been made. Most cases showed a characteristic autoantibody profile of antinuclear antibody, rheumatoid factor, and antibodies to Ro and La. Sjögren's syndrome was diagnosed as 'definite' in 16 cases and 'possible' in seven cases by Fox's criteria. The remainder had unclassified connective tissue disease (three), rheumatoid arthritis with dry eyes (two), SLE (one), scleroderma (two), and Raynaud's disease (one). Extraglandular features were invariably present in patients with primary Sjögren's syndrome. The highest concentrations of IgG1 were found in patients with the shortest disease duration. Selective polyclonal increase of IgG1 should alert the doctor to the development of Sjögren's syndrome, usually with extraglandular disease and antibodies to Ro and La.

Acute-Phase Reaction↗
PubMed1990

Humoral autoimmunity in systemic rheumatic disease. A review.

'Antinuclear antibody' is a term now encompassing more than a dozen specificities, and cheap tests for these autoantibodies are readily available. Taken together with the clinical picture the tests can help in the fine tuning of diagnosis and perhaps prognosis within the connective tissue diseases. Certain anticellular antibodies appear to identify particular disease subsets and overlap syndromes, and their detection in conditions such as congenital heart block and recurrent abortion points to the presence there of autoimmune mechanisms. The antibody-disease relationships are reviewed here and the underlying mechanisms are explored. Associations between antibodies themselves and the paucity of evidence for direct pathogenetic effects in many cases leave open the possibility that antinuclear antibodies are clues to aetiology, reporters of a past event initiating both disease and autoantibody production. Retroviruses are candidates fast coming under scrutiny. Arcane though names such as Ro, La, Sm and Jo-1 may appear, much is now known about the intracellular targets of the antibodies; most are enzymes or particles active in DNA replication and the synthesis of RNA and protein. Hence, autoantibodies are useful tools for the molecular biologist as well as the clinician. New knowledge about autoantibodies may yield insights into the aetiology, as well as the pathogenesis, of systemic rheumatic diseases.

Animals↗
PubMed1989

Epitope mapping of the cloned human autoantigen, histidyl-tRNA synthetase. Analysis of the myositis-associated anti-Jo-1 autoimmune response.

Autoantibodies that bind aminoacyl-tRNA synthetases are strongly associated with the human inflammatory myopathies polymyositis and dermatomyositis, but their molecular origins and relationship to pathogenesis are not known. To address these issues, we wished to identify the autoantigenic epitopes which react with these autoantibodies and to this end, we previously isolated a full length cDNA clone encoding the target Ag recognized most frequently by myositis sera, histidyl-tRNA synthetase (HRS). In the present study, we have analyzed the HRS autoepitopes by two amino acid insertion linker mutagenesis of HRS proteins expressed in Cos 1 cells. A series of mutant HRS cDNA were constructed and the expressed proteins were tested for enzyme activity and for immune reactivity with a panel of sera with anti-Jo-1 antibodies. Immunoblotting and immunoprecipitation analyses revealed that anti-Jo-1 antibodies recognize multiple conformation-dependent and independent epitopes on HRS and that the autoepitopes vary among different myositis patients.

Amino Acyl-tRNA Synthetases↗
PubMed1989

Short-duration, high-dose urokinase infusion for recanalization of occluded saphenous aortocoronary bypass grafts.

Thrombolytic recanalization of arterial bypass grafts has been pursued aggressively in the peripheral circulation but not in the coronary circulation. In an attempt to apply peripheral transcatheter thrombolytic techniques to the coronary circulation, nine patients with 10 occluded saphenous aortocoronary bypass grafts underwent recanalization procedures using a short-duration, high-dose urokinase infusion. Urokinase was infused at the occluded graft orifice at a rate of 600 units/min. The average infusion time was 1 hr, 26 min. The average urokinase dose was 435,000 units. Graft recanalization was achieved in eight (80%) of 10 grafts, although only six (60%) of 10 grafts were widely patent at the end of the procedure. All successfully recanalized grafts required balloon angioplasty of underlying stenoses. No complications, specifically myocardial infarction or cerebrovascular accident, were encountered. We have shown that occluded aortocoronary bypass grafts can be recanalized successfully by using a short-duration, high-dose urokinase infusion. It appears that, with attention given to angiographic techniques that minimize clot manipulation, recanalization can be accomplished safely in a majority of cases.

Adult↗
PubMed1988

A record-keeping format for training systemic therapists.

Training in systemic therapy necessitates a structured approach to teaching systemic thinking. The Systemic Therapy Sessions Summary Form, a record-keeping method, is presented as a tool for enhancing training in systemic therapy. The purpose of this form is to provide the structure for the trainee to develop circular hypotheses, to connect reflexively the assessment and intervention components of therapy, and to maintain a sense of the evolving nature of therapy across sessions. A case example illustrates the use of this record-keeping format.

Education, Continuing↗
PubMed1988

An IgG subclass imbalance in connective tissue disease.

A group of 16 patients with a disproportionate polyclonal increase in their serum IgG1, resulting in raised concentrations of total IgG immunoglobulin, has been discovered. The other IgG subclasses in these patients are either normal or slightly reduced, resulting in an IgG1:IgG2 ratio of at least 10:1. Most cases are marked by the presence of anti-extractable nuclear antigen (anti-ENA) antibodies and high titres of rheumatoid factor and antinuclear antibody. All but one patient has a connective tissue disease, nearly twice the prevalence found in similarly hypergammaglobulinaemic patients without this IgG subclass imbalance. Among patients with systemic lupus erythematosus (SLE), those with the IgG1 disorder have a higher prevalence of high titre rheumatoid factor and antinuclear antibody, but a lower prevalence of anti-double-stranded DNA (anti-dsDNA) antibodies above 30 U/ml. It is suggested that this immunoglobulin abnormality may reflect a unique immunoregulatory dysfunction in these patients.

Adolescent↗
PubMed1988

Surfactant replacement therapy at birth: final analysis of a clinical trial and comparisons with similar trials.

A randomized trial of surfactant replacement therapy at birth was conducted at the University of Rochester between June 1983 and November 1985. Thirty-four premature infants, 25 to 29 weeks' gestational age, received a preventilatory dose of a calf lung surfactant extract in saline prepared at the University of Rochester. A control group of 31 infants received a preventilatory dose of saline alone. The major finding of this trial is that a single preventilatory dose of calf lung surfactant extract reduces the severity of the respiratory distress syndrome during the first 24 hours of life. The beneficial effects, however, are not sustained in many infants and diminish after 24 hours of life. The survival rate was 71% in both the control and surfactant-treated groups. There was a lower incidence of pneumothorax in the surfactant-treated group. There were no differences in the incidence of bronchopulmonary dysplasia, patent ductus arteriosus, and intraventricular hemorrhage. No adverse effects of surfactant replacement therapy were identified. Results of this study suggest that multiple postventilatory doses of surfactant will be required for optimal therapy.

Clinical Trials as Topic↗
PubMed1987

Autoantigenic histone epitopes: a comparison between procainamide- and hydralazine-induced lupus.

Using the technique of immunoblotting, we assessed the ability of sera from 19 patients with drug-induced lupus to bind individual histones and specific histone fragments. The pattern of histone epitopes bound by sera from 9 patients with procainamide-induced lupus was very similar to that described previously in spontaneous systemic lupus erythematosus. In contrast, sera from 10 patients with hydralazine-induced lupus bound a broader array of individual histones and recognized a different set of histone epitopes. We conclude that these 2 drugs induce antihistone antibodies through somewhat different mechanisms, which possibly involve differences in their ability to structurally alter chromatin.

Autoantigens↗
PubMed1987

Antibodies to the five histones and poly(adenosine diphosphate-ribose) in drug induced lupus: implications for pathogenesis.

Certain drugs are a frequent source of antinuclear antibody (ANA) induction, and ANA is invariably present in the few patients who progress to the drug induced lupus syndrome. This report concerns the fine specificity of the ANA response to hydralazine, penicillamine, and sulphasalazine therapy. Using highly purified individual histones in fluorimetric assays, antihistone antibodies are always detectable, often in large amounts, but the pattern of response to individual histones is variable and not drug specific. In addition to the response to the three histones H1, H2B, and H3 reminiscent of idiopathic systemic lupus erythematosus, antibody to histone H2A predominates in some drug induced cases. Contrary to previous thought, histones are not the sole target of the antinuclear response: we also demonstrate a significant correlation between ANA titre and antibody to poly(adenosine diphosphate-ribose). Like the histones, this is a macromolecule that can bind to deoxyribonucleic acid (DNA). It is proposed that drug induced damage to chromatin leads to ANA production, while drug induced impairment of complement activity may then enable these autoantibodies to mediate the lupus syndrome.

Antibodies, Antinuclear↗
PubMed1987

Immunoglobulin G subclass distribution of autoantibodies in systemic sclerosis, primary biliary cirrhosis, and overlap syndromes.

The IgG subclass reactivities of six anticellular antibodies were measured by indirect immunofluorescence on HEp2 cells using murine monoclonal antibodies to the four human IgG subclasses. Patients with scleroderma, primary biliary cirrhosis (PBC), systemic lupus erythematosus, and mixed connective tissue disease were studied. Anticentromere antibody (ACA) was virtually all IgG1 and 3; antibody to multiple nuclear dots (NSpI) was IgG1, 2, and 3; antimitochondrial antibody was mainly IgG2 and 3; nucleolar staining was varied in subclass reactivity but most often IgG4; the diffusely grainy staining associated with Scl-70 antibody was chiefly IgG1; and the speckled pattern associated with anti-RNP antibody was always IgG1 and 4, with IgG2 and 3 in some cases. These data fail to support the hypothesis that the various patterns of autoimmune disease reflect differences in the biological properties of the associated antibodies. The prominence of IgG2 in antibodies associated with PBC suggests the possibility of an immune response independent of T cells in that condition. Differential subclass staining showed an unexpectedly high frequency of antibody to multiple nuclear dots in ACA positive sera, and such patients (all with CREST syndrome) could be at increased risk of developing PBC later.

Antibodies, Antinuclear↗
PubMed1987

Autoantibodies to intracellular antigens, with particular reference to transfer RNA and related proteins in myositis.

The common autoantibody systems are relatively few in number. The antibodies often exhibit associations with particular diseases and with one another. Furthermore, many of the corresponding antigens also exhibit striking biochemical interrelationships. In some cases the antigens comprise elements of a macromolecular complex or particle, suggesting that the complexes are likely to be the immunogens. The complexes frequently contain or interact with nucleic acids. Detailed analysis of the nature of the antigens and their interactions with autoantibodies offers promising insights into the origin of the antibodies and of autoimmune disease. This thesis is illustrated with particular reference to the myositis specific antigens.

Antibody Specificity↗
PubMed1986

Autoantibodies against alanyl-tRNA synthetase and tRNAAla coexist and are associated with myositis.

The sera of six patients with autoimmune disease, predominantly myositis with pulmonary fibrosis, contain antibodies of the PL-12 specificity. These autoantibodies react with both protein and RNA components of human cells. The protein has a subunit molecular mass of 110 kD, and the RNA comprises a group of bands in the tRNA size class. Aminoacylation experiments identify the antigens as alanyl-tRNA synthetase and its corresponding tRNAs, tRNAAla. Anti-tRNA antibody can be absorbed out without depleting antisynthetase activity, showing that the antigens are recognized independently by separable antibodies that coexist in these sera. The concurrence of separate antibodies to the two components suggests that the autoimmune response may be mounted against the charging enzyme-tRNA complex. However, the antisynthetase antibody fails to coprecipitate tRNA with the enzyme, suggesting that the antibody reacts with its target only when it is not complexed with tRNA.

Adult↗
PubMed1986

The SL autoantibody-antigen system: clinical and biochemical studies.

A recently described autoantibody, SL, was found in serum from 27 patients with autoimmune disease, including 20 with systemic lupus erythematosus (SLE) where the frequently was 7%. Analysis of clinical, serological, and HLA data from 119 SLE patients showed no positive associations with anti-SL antibody apart from a higher frequency of non-infective fever. Most SL positive sera contained other precipitins, notably antibodies to Ro(SS-A) and the proliferating cell nuclear antigen, PCNA. Anti-SL IgG recognised a protein of 32 000 daltons without associated RNA. This polypeptide was distinguished from a similarly sized component of the Sm and RNP ribonucleoprotein particles by demonstrating different products of partial proteolysis. Although anti-SL antibody is of limited clinical importance, it occurs with twice the frequency of anti-SM antibody in white patients with SLE. Preliminary studies indicate that SL and the Japanese Ki system are identical.

Antibodies, Antinuclear↗
PubMed1985

Patterns of antihistone antibody specificity in systemic rheumatic disease. I Systemic lupus erythematosus, mixed connective tissue disease, primary sicca syndrome, and rheumatoid arthritis with vasculitis.

A new fluorimetric assay was used to measure the relative amounts of antibodies to individual nuclear histones in sera from 102 patients with systemic lupus erythematosus (SLE), mixed connective tissue disease, primary sicca syndrome, and rheumatoid arthritis with vasculitis. In SLE sera, the predominant responses were to histones H-1, H-2B, and H-3, with marked elevations of binding to H-1 and H-2B in one-third of the patients, and to H-3 in one-fourth; antibodies of both the IgG and IgM classes were also detected. In a few SLE sera, the pattern of histone response differed or was restricted to 1 immunoglobulin class. In mixed connective tissue disease, only 2 of 9 sera showed elevated histone binding activity, the response being predominantly to H-3 in 1 patient and to H-1 and H-2B in the other. Binding to H-2B was also prominent in 2 of 3 patients with primary sicca syndrome. The highest antihistone reactivity and the most heterogeneous response patterns were observed in patients who had rheumatoid arthritis with vasculitis; 6 of 8 of those sera had elevated histone reactivity. In SLE, the highest histone binding results were found among patients with a history of photosensitivity. Histones are closely associated with DNA in the nucleosome, and we speculate that antihistone antibodies could arise as a result of damage to DNA, induced by drugs or irradiation.

Antibodies↗