Search PubMed⌕ Search

Biomedical subjects

M J Rowley

Publications and source records attributed to M J Rowley.

At least 109 records · Page 6Linked to original sources
PubMed1991

Anti-neutrophil cytoplasm antibodies in rheumatoid arthritis.

Anti-neutrophil cytoplasm antibodies (ANCA) occur occasionally in rheumatoid arthritis (RA), but their incidence and clinical significance have been unclear. In this study we have investigated 58 patients with RA. In 22 patients the disease was inactive and the remaining 36 with active disease were further subdivided into those without clinical evidence of vasculitis (26), those with cutaneous vasculitis (8) and those with systemic vasculitis (2). ANCA were demonstrated by indirect immunofluorescence in 10 of the 58 patients (17%). While both perinuclear (pANCA) and cytoplasmic (cANCA) staining were detected, pANCA were more common (70%). Neutrophil-specific anti-nuclear antibodies (ANNA) were demonstrated in a further eight sera (14%) and ANA were detected on Hep-2 cells in 30 of the 58 sera (52%). ELISAs for the detection of anti-myeloperoxidase and anti-elastase antibodies were then established. Five sera with pANCA and five that contained ANNA were negative for both anti-myeloperoxidase and anti-elastase antibodies, suggesting other as yet unidentified cytoplasmic antigens as the target molecules. However, anti-myeloperoxidase or anti-elastase antibodies were found in four sera that had homogeneous or speckled ANA on both Hep-2 cells and neutrophils. One serum contained both antibodies. The presence of ANCA detected by indirect immunofluorescence or of anti-myeloperoxidase or anti-elastase antibodies in these patients with RA was not associated with disease activity nor with the demonstration of cutaneous vasculitis or renal disease (P NS). A possible association with systemic vasculitis remains to be confirmed. There is an incomplete correlation between indirect immunofluorescence patterns and antibody specificity in ELISA systems.

Antibodies, Antinuclear↗
PubMed1991

An automated microassay for enzyme inhibitory effects of M2 antibodies in primary biliary cirrhosis.

In primary biliary cirrhosis (PBC), autoantibodies are produced to the M2 group of mitochondrial antigens, of which a major constituent is the E2 subunit of the pyruvate dehydrogenase complex (PDC). These antibodies, in addition to conventional reactivities with PDC, characteristically inhibit the catalytic function of PDC in vitro, as judged by a macroinhibition assay based on spectrophotometry. We describe a microinhibition assay adapted for microtitre plates and for an automated readout of results by an ELISA plate reader. We show that this microassay has a sensitivity similar to that of the macroassay. In a study of 83 sera, from PBC and other diseases, the inhibitory microassay proved specific for PBC. This automated inhibitory microassay for PBC-sera could become a primary laboratory procedure for the diagnosis of PBC, particularly because it may identify antibodies to the actual autoepitope on the PDC-E2.

Animals↗
PubMed1991

Autoantibody against dihydrolipoamide dehydrogenase, the E3 subunit of the 2-oxoacid dehydrogenase complexes: significance for primary biliary cirrhosis.

Autoantibodies in primary biliary cirrhosis recognize mitochondrial 2-oxacid dehydrogenase complexes, particularly the E2 subunits. Reactivity with the E3 subunit, common to each of the enzyme complexes, was sought by immunoblotting, with sera screened at 1:100 instead of the conventional 1:1,000 dilution. This was found in 11 of 29 sera from patients with primary biliary cirrhosis but also in 10 of 40 sera from normal subjects. Two-dimensional immunoblotting and immunoblotting on purified enzymes established that the reactivity was actually with E3 rather than with another component of the 2-oxoacid enzymes of similar molecular weight. Purified antibodies to E3 eluted from an affinity column did not cross-react with other components of the 2-oxoacid enzyme complexes. The antibodies to E3 did not react with the Escherichia coli or yeast E3 subunits, suggesting that they are not stimulated by immune responses against microorganisms. Thus the proposal that reactivity to the shared E3 subunit of the 2-oxoacid enzyme complexes could initiate primary biliary cirrhosis is not reflected at the antibody level.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1990

Associations between HLA and antibodies to collagen in rheumatoid arthritis.

Associations between HLA types and serum antibodies to native and denatured type II collagen were sought in 105 patients with rheumatoid arthritis (RA). Antibodies were measured using a solid phase radioimmunoassay. There were no significant associations between any HLA antigen (A, B, or DR) and a high antibody titre to native collagen. There were significant associations, however, between HLA antigens and high antibody titres to denatured collagen. Although DR4 did not show an association, the phenotype A2+DR4+ did; this was not related to A2 as A2+DR- was not associated with a high antibody titre. No single B locus antigen showed an association, but several B locus antigens, B12, B15, and B40, were included in phenotypes with A2 and DR4 which were associated with a high antibody titre to denatured collagen. These HLA associations with anticollagen type II are best explained by a gene other than DR4 (but in linkage with it) which may regulate the antibody response to denatured collagen. If so, this would represent an HLA gene in addition to DR4 that is active in RA.

Antibodies↗
PubMed1989

Activity of rheumatoid arthritis and levels of collagen antibodies: a prospective study.

Thirty-seven patients with classical or definite rheumatoid arthritis (RA) were studied prospectively over a period of 12 months to assess whether there was a relationship between disease activity and raised levels of antibodies to native or denatured type II collagen. Nineteen patients had inactive RA according to ARA criteria for disease remission and 18 had active RA throughout the study. At the beginning of the study the levels of collagen antibodies were comparable in each group. After 1 year, antibodies to denatured type II collagen in patients with inactive RA had declined to significantly lower levels whereas in patients with active RA the levels of antibodies fluctuated during the period of study and were not significantly different at the end. There was no relationship between levels of antibodies to type II collagen and any specific index of disease activity, severity of X-ray changes in the hands and feet, or progression over 1 year in X-ray changes. The finding of a decline in levels of antibodies to denatured type II collagen in inactive RA suggests that the anticollagen response is an integral component of the rheumatoid process and could have a primary or secondary role in pathogenesis.

Adult↗
PubMed1988

Premises for immune interventional therapy in rheumatoid arthritis.

Consideration of rheumatoid arthritis (RA) as an autoimmune disease includes initiating event(s), genetic predisposition, immune regulatory derangements, and effector cycles of articular damage. The initiating event is still unknown. Collagen type 2 has good claims as a rheumatogenic autoantigen which perpetuates disease. The association of HLA DR4 with rheumatoid arthritis is in part explainable by the affinity of binding of the rheumatogenic antigen to a hypervariable portion of MHC Class II molecules with selective presentation of this complex to T cell receptors. Immune regulatory derangements include lymphokine-induced aberrant expression of MHC Class II molecules on synovial tissues, the presence of a 'resistant' subset of B cells (CD5 + ve), failure of anti-idiotypic control of autoantibodies (not well established as yet in rheumatoid arthritis), and defective immune suppression, revealed by low counts in synovial fluids of a suppressor-inducer subset of CD4 + ve T cells. The many possibilities for therapeutic immune intervention would include polyclonal or monoclonal antibody to block (a) receptors for antigen on B or T lymphocytes (but this would require knowledge of the rheumatoid arthritis-inducing antigen), (b) the CD4 complex on helper T lymphocytes, (c) MHC Class II (Ia) molecules, for which there are excellent prototypes in experimental immunopathology, or (d) lymphokines or their receptors. Induction of suppression by 'tolerogenic vaccines' is experimentally validated, but only for diseases for which an autoantigen can be identified.

Arthritis, Rheumatoid↗
PubMed1988

Collagen antibodies in juvenile arthritis and adult rheumatoid arthritis: differences in levels and type-specificity.

Antibodies to both native and denatured type II collagen were measured in the serum of 63 patients with juvenile onset arthritis (JA) and in 67 patients with adult onset rheumatoid arthritis (RA). Levels of antibodies in the 2 groups were compared with antibody levels in 30 healthy adult controls, and in 20 children with nonrheumatic diseases. Antibodies to denatured and native collagen were increased in RA but not in JA. There was no apparent difference between the collagen antibody levels in any of the 3 subgroups of JA, pauciarticular, polyarticular or systemic onset disease. Antibodies to denatured collagen were not type specific, and reacted similarly with type I and type II collagens, but antibodies to native collagen were much more specific, and most reacted more strongly on type II collagen than on type I collagen. Our results, unlike those in previous reports, imply that antibodies to collagen are infrequent in JA and hence cannot be implicated in the pathogenesis of that disease, which is in contrast to adult onset RA.

Adolescent↗
PubMed1987

Evidence for local synthesis of antibodies to denatured collagen in the synovium in rheumatoid arthritis.

Synovial fluid samples from 36 patients with rheumatoid arthritis (RA) and 31 patients with other articular diseases (OAD) were examined for the presence of antibodies to denatured or native human type II collagen. Levels of IgG antibodies to denatured or native human type II collagen, rheumatoid factor, immunoglobulins, and total proteins were assessed in paired samples of serum and synovial fluid from 21 patients with RA and from 14 patients with OAD. Solid-phase radioimmunoassay showed that levels of antibodies to denatured collagen in synovial fluid were significantly higher in RA patients than in OAD patients (median 3,270, range 44-16,816 versus median 919, range 119-5,814; P less than 0.001). These antibody levels were higher in synovial fluid than in the serum of RA patients, but not in patients with OAD. Paired serum and synovial fluid samples showed no correlation between the level of antibodies to denatured collagen and levels of either IgG, IgA, IgM, or rheumatoid factor. Synovial fluid antibodies to native collagen were higher in RA patients. Antibodies to collagen may be synthesized preferentially in synovial tissues and, hence, participate in the perpetuation of RA.

Adult↗
PubMed1987

Collagen antibodies in Ross River virus disease (epidemic polyarthritis).

Antibody activity against collagen was measured in 53 samples of serum from 48 patients with active signs of epidemic polyarthritis (EPA) following infection with Ross River virus. Activity was higher against denatured collagen than against native collagen, but was within the normal range for each. Determination of HLA phenotypes permitted a search for any relationship between HLA type and differences in collagen antibody levels within the normal range. No relationship was detected with HLA antigens predominating in EPA or with HLA antigens that are associated with high collagen-antibody levels in rheumatoid arthritis (RA), which suggests that the latter associations may represent failure to control collagen antibody levels after the onset of RA. The findings also provide evidence against a role for nonspecific enhancement of humoral immune responses in the pathogenesis of EPA, and constitute a further point of distinction between EPA and RA.

Adolescent↗
PubMed1976

Bone trauma and related benign disease: assessment by bone scanning.

The radionuclide investigation of skeletal trauma in the past was confined generally to scintimetry and an occasional bone scan. The development of improved radiopharmaceuticals, including 99mTc-labeled compounds with their enhanced sensitivity, and the refinement of imaging devices offering superior resolution and speed have allowed a more detailed assessment of conditions resulting from trauma. Practical approaches to the diagnosis of subtle bone injury resulting in stress fracture, the differentiation between delayed healing and nonunion, and early recognition of avascular necrosis and osteomyelitis are now available. The changing pattern of radionuclide uptake in bone following damage by radiation and other abnormalities as a consequence of trauma also can be easily studied.

Adolescent↗
PubMed1975

Comparison of 85Sr, 87mSr, 18F, and 99mTc-labeled phosphates for bone scanning.

The observation by Subramanian and his co-workers that a 99mTc-labeled polyphosphate had excellent affinity for bone has led to widespread use of 99mTc-labeled phosphates as bone scanning agents. Initially, only polyphosphate was employed, but because of somewhat inconstant results and difficulty in preparation of this product, other phosphate compounds were sought. We soon discovered that an inorganic compound, pyrophosphate, appeared to have certain advantages over polyphosphate. Other workers formulated diphosphonates (organic phosphates) which also demonstrated advantages over polyphosphates. Comparison studies in rabbits utilizing 85Sr, 87mSr, 18F, and several phosphates (inorganic and organic) proved the 99mTc-labeled phosphates to be clearly superior in delineating normal skeletal anatomy. Studies in humans confirmed that excellent visualization of bone was obtained with 99mTc-labeled phosphates using either a gamma camera or a rectilinear scanner. What was not known, however, was just how reliable this class of agents would prove to be in detecting bone disease when compared to bone-seeking radiopharmaceuticals such as 85Sr, 87mSr, and 18F. Further comparative analyses have clearly demonstrated that both inorganic and organic 99mTc phosphate complexes are extremely sensitive in revealing more bone disease than the older bone scanning agents.

Adult↗