Search PubMed⌕ Search

Biomedical subjects

L Schrieber

Publications and source records attributed to L Schrieber.

At least 55 records · Page 3Linked to original sources
PubMed1988

An evaluation of the role of laboratory investigations in establishing a diagnosis of central nervous system lupus.

By means of a questionnaire, we have determined the combination of clinical features and laboratory tests which rheumatologists, nephrologists, immunologists, and neurologists in New South Wales consider most helpful in discriminating between central nervous system (CNS) involvement due to systemic lupus erythematosus (SLE) and that due to other causes. There was a uniformity of views amongst the four specialties in terms of the likelihood that a given clinical presentation was due to active CNS lupus. The clinical presentation made little difference to the interpretation of laboratory data. CNS abnormalities (EEG, CT, and CSF), as well as the finding of serum DNA antibody of 95%, influenced decision-making, although the other serological tests had little impact. There was disagreement amongst physicians as to whether a given test abnormality (e.g. focal CT scan abnormality) supported or rejected the diagnosis of active CNS lupus. This study indicates that physicians interpret test results selectively in their assessment of patients with SLE who develop CNS symptoms.

Brain Diseases↗
PubMed1988

Immunosuppressive drugs and corticosteroids in the treatment of rheumatoid arthritis.

Rheumatoid arthritis is the most common form of severe inflammatory arthropathy affecting patients at a relatively early age. Although there are a number of drugs which significantly reduce pain and swelling, few alter the development of erosions and progression of joint destruction. A significant number of patients with rheumatoid arthritis develop this progressive disability and will require treatment with corticosteroids or immunosuppressive agents. In this article the use of immunosuppressive drugs and corticosteroids in the treatment of aggressive rheumatoid arthritis is reviewed. Controlled clinical trials have shown that a number of these drugs can play a significant role in reducing pain and swelling and might possibly alter the disease course in rheumatoid arthritis. Side effects of these agents, including the potential for oncogenesis, still pose major problems in their long term use. The risks and benefits of immunosuppressive and corticosteroid drug therapy must be balanced in each patient to whom they are prescribed and reviewed at frequent intervals.

Adrenal Cortex Hormones↗
PubMed1988

Relationship of age and sex to autoantibody expression in MRL-+/+ and MRL-lpr/lpr mice: demonstration of an association between the expression of antibodies to histones, denatured DNA and Sm in MRL-+/+ mice.

Despite the protean nature of the clinical characteristics of systemic lupus erythematosus (SLE), autoantibodies represent an almost constant feature. Furthermore they are common to both human SLE and murine lupus. Nonetheless, the mechanism by which they arise has not been established. Amongst the several processes that have been proposed, evidence has emerged supporting specific antigen drive as a significant mechanism. We have documented the age- and sex-related differences in the prevalence of antibodies to both chromatin-related (histone and DNA) and non-chromatin-related (Sm) antigens in MRL mice. Our finding of an association between antihistone antibodies and anti-denatured DNA antibodies is consistent with chromatin being the putative antigen. Additionally, antibodies to the individual histones H1 and H2B, the most exposed histones in chromatin, were more prevalent than antibodies to the remaining histones (H2A, H3, H4). This, again, supports specific antigen drive as a mechanism for autoantibody production. However, associations were also found between antibodies to histone and DNA and antibodies to Sm. As Sm is a non-chromatin protein antigen, the associations between antibodies to Sm and those to histone and DNA suggest that mechanisms in addition to specific antigen drive are important in autoantibody production.

Aging↗
PubMed1987

Interstitial lung disease as the presentation of anti-Jo-1 positive polymyositis.

A patient presenting with interstitial lung disease was predicted to have underlying polymyositis when found to be anti-Jo-1 antibody positive. When myopathy developed later with elevated serum creatine phosphokinase and myoglobin levels, the electromyogram was nonmyopathic, and polymyositis was confirmed by muscle biopsy. The case illustrates the value of anti-Jo-1 as a 'marker' autoantibody for polymyositis, and the need for thorough investigation of patients with interstitial lung disease of uncertain etiology. This should include indirect immunofluorescence using a dividing cell substrate and tests for antibodies to extractable tissue antigens. The need to completely evaluate patients with dermatopolymyositis is also emphasised.

Aged↗
PubMed1987

Soluble immune complexes in lupus mice: clearance from blood and estimation of formation rates.

Elevated levels of circulating immune complexes (IC) occur in patients with systemic lupus erythematosus (SLE) and in several strains of mice that spontaneously develop a lupus-like illness. An increase in circulating IC might occur as a result of increased IC formation or decreased IC clearance. Previous work with one murine lupus strain, NZB/W, demonstrated normal clearance of soluble IC. We studied the in vivo behavior of stable model IgG IC in two murine lupus strains. MRL/l and BXSB, and in two normal strains, C3H/HeN and BALB/c. IC were injected intravenously, and blood radioactivity was measured over 3 hr. A clearance curve was derived for each mouse using the Marquardt-Levenberg curve-fitting method. A formula is derived which predicts the formation rate of IC in each animal from the blood level of IC and the clearance curve parameters. All mice exhibited biphasic exponential clearance of IC over 3 hr. Clearance of IC was significantly slower in MRL/l mice than in normal strains (P less than 0.02), and clearance in BXSB mice was significantly faster than in normals (P less than 0.02). However, the derived formula suggests that the observed differences in IC clearance have only a small effect on the blood levels of IC in the mice studied, and therefore suggests that the major factor which accounts for increased blood levels of IC in lupus mice is an increase in the IC formation rate.

Albumins↗
PubMed1987

Hypothesis: lymphocyte trafficking in inflammatory rheumatic disease. A role for receptor mediated homing.

The entry of lymphocytes into normal lymph nodes occurs principally after their passage across postcapillary high endothelial venules. Nonlymphoidal tissues do not normally express high endothelial venules; however, in inflammatory rheumatic diseases associated with prominent lymphocyte accumulation (e.g., rheumatoid synovium), high endothelial venule-like structures are found and may facilitate local lymphocyte traffic. In mouse and man there are lymphocyte surface membrane homing receptors which determine lymphocyte binding to acceptor sites on lymph node high endothelial venules. The migration of lymphocytes from the circulation into inflamed nonlymphoidal tissues may be controlled by similar homing receptor mediated mechanisms.

Adrenal Cortex Hormones↗
PubMed1986

Aberrant lymphocyte trafficking in murine systemic lupus erythematosus.

The patterns of migration of lymphoid cells from autoimmune-prone MRL-lpr/lpr, C57BL/6-lpr/lpr, MRL-+/+, and NZB mice were compared to those from sex and age-matched, normal CBA, C57BL/6, and BALB/C mice. Chromium-51-labelled spleen and lymph node cells from all autoimmune mice tested homed preferentially to the spleen relative to lymph node of the recipient strain. The data indicate that defects in lymphocyte trafficking are widespread in murine lupus and suggest a role for abnormal lymphocyte migration in the pathogenesis of this disease.

Age Factors↗
PubMed1986

Anti-C1q affinity isolated circulating immune complexes correlate with extra-articular rheumatoid disease.

Circulating immune complexes (CIC) were isolated from sera of 35 patients with rheumatoid arthritis (RA) by a two-step method using 2% polyethylene glycol precipitation and anti-C1q affinity chromatography. By this method CIC were exclusive to 19 patients with vasculitis, nodules, or Sjögren's syndrome. Levels of CIC did not correlate with the severity of synovitis but reflected the extent of extra-articular disease. Furthermore, in four patients with persistent severe synovitis observed over a period of 4 to 16 months, the levels of CIC paralleled changes in extra-articular disease. Despite such additional evidence, whether the relationship between CIC and tissue injury is causative or consequential remains unresolved.

Aged↗
PubMed1986

Current concepts in the etiopathogenesis and treatment of systemic lupus erythematosus (SLE).

Systemic lupus erythematosus is an autoimmune disorder that occurs spontaneously in humans and mice. Genetic factors play an important role in the predisposition to and expression of disease. Environmental factors augment the expression of illness and in the absence of normal control mechanisms may provide the stimulus to autoimmunity. Sex hormones modulate the immune response and tend to modify disease expression. Disordered immune regulation may be due to a primary or secondary abnormality in cellular, cytokine, and/or humoral function. Therapy for SLE is directed towards suppression of exaggerated immunological and inflammatory activity. This review will re-evaluate current therapy and describe newer approaches including the use of pharmacological, hormonal, immunological, dietary, and physical modalities.

Humans↗
PubMed1985

Failure of methotrexate and methylprednisolone to alter the clearance of model immune complexes.

We evaluated the effect of methotrexate (MTX) and methylprednisolone (MP) on reticuloendothelial system (RES) clearance of soluble model immune complexes (IC) in BALB/C mice. MTX was administered by intraperitoneal route either as a single dose (0.5 mg/kg) or as 10 alternate day doses (0.1 or 0.5 mg/kg), MP as a single intravenous (IV) bolus (50 mg/kg) with normal saline used as a control. Mice were then injected IV with radiolabelled IgG anti-DNP covalently crosslinked IC. Blood radioactivity was measured over a 3 h period at which time organ uptake, corrected for blood contamination, was determined. Clearance curves for each mouse were derived using the Marquardt-Levenberg curve fitting method. No significant differences in IC clearance or organ uptake were found between drug and control groups at any drug dose or time period. Our findings argue against an influence of MP and MTX on immunospecific clearance of soluble IC.

Animals↗
PubMed1984

Factors influencing immune complex localisation.

In systemic immune complex (IC) diseases such as SLE and rheumatoid vasculitis, IC accumulate in a number of tissues, either after deposition from the circulation or from in situ formation. The tissue localisation of IC depends on a delicate balance between the production of IC and the ability of the mononuclear phagocytic system (MPS) to remove them from blood. At times IC are cleared inefficiently, persist in the circulation and subsequently localise in tissues. This review evaluates the role of local tissue factors - anatomical, physiological, physical and immunological - in this process. We report on our studies examining the significance of C3b and IgG Fc receptors in tissues subject to IC deposition. No evidence for such receptors was found with the exception of a C3b receptor in human glomeruli. Our negative findings may be due to methodological difficulties in the identification of in situ receptors. Alternatively, immune receptors may not be present at these extra-glomerular sites and would therefore be unlikely to participate in IC localisation.

Animals↗
PubMed1984

Tissue uptake and catabolic studies of 125I SS-B (La) injected into mice.

The radiolabeled soluble cellular antigen 125I SS-B (La) has a plasma half-life of 3 min following iv injection into BALB/C mice. Uptake by Kupffer cells (KC) and proximal renal tubular (PRT) cells was demonstrated by autoradiography (ARG). That trichloracetic acid (TCA)-soluble products of 125I SS-B appeared in plasma within 1 min of iv injection suggests rapid in vivo breakdown. Activated peritoneal macrophages (APM) degraded 125I SS-B in a time- and cell-dose-dependent fashion. These findings suggest that the plasma clearance and catabolism of 125I SS-B may be dependent on its interaction with phagocytic cells. This rapid antigen elimination may protect against harmful autoantibody responses.

Animals↗
PubMed1984

NIH conference. Rheumatoid arthritis: evolving concepts of pathogenesis and treatment.

Rheumatoid arthritis is a chronic inflammatory synovitis that primarily involves peripheral diarthrodial joints. Immunohistologic analysis of diseased synovium has shown a spectrum of abnormalities that resemble various stages of a cell-mediated, or delayed-type, immune reaction. The infiltrating mononuclear cells produce various factors that modulate adjacent tissues and appear to produce the characteristic destructive features of the disorder. Our understanding of the mechanisms of action of various therapeutic modes also indicates that the disease is primarily mediated by activated mononuclear cells. All effective therapies have been shown to affect either mononuclear cell function or the rates of production or elimination of these cells. The disorder likely represents the pathologic expression of a genetically controlled host immune response to an undefined causative stimulus. The stimulus could be an infectious agent(s), a product(s) derived from an infectious agent(s), a constituent(s) of synovial or connective tissue, or a combination of these.

Animals↗
PubMed1984

Specific autoantibody slows the rapid plasma clearance of 125I-SS-B (La) in mice.

In BALB/c mice the plasma clearance of intravenously (i.v.) injected 125I-SS-B (La) (T 1/2 = 3 min) is markedly delayed when complexed in vitro to specific autoantibody (T 1/2 = 60 min) and is associated with diminished hepatic and renal uptake. The in vivo behaviour of 11S 125I-SS-B-IgG-anti-SS-B complexes was similar to that of 20-30S 125I-heat-aggregated IgG. The presence of anti-SS-B antibodies in systemic lupus erythematosus and Sjögren's syndrome could similarly result in persistence of SS-B containing immune complexes and provide a mechanism which may perpetuate autoimmunity.

Animals↗