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Biomedical subjects

R D Inman

Publications and source records attributed to R D Inman.

At least 55 records · Page 3Linked to original sources
PubMed1994

Etiopathogenesis of ankylosing spondylitis and reactive arthritis.

In ankylosing spondylitis and reactive arthritis, an interplay of microbe and major histocompatibility complex initiates a sequence of events resulting in chronic inflammation. With the use of molecular probes as direct evidence and immune response patterns as indirect evidence, a strong case has been made for a central role of local microbial antigen in reactive arthritis. Cofactors such as gender, persistent gut inflammation, and antibiotic treatment may contribute to this process. Studies of transgenic rats and of familial spondylitis implicate B27 itself as the critical host variable. The results of recent studies point to intimate B27-bacteria interrelationships. HLA-B27 and proteins from enteric bacteria are structurally related, in a manner that may affect T cell response to enteric pathogens. B27 also may directly affect host-microbe interactions by modulating the invasive potential of these bacteria into target cells. Studies are in progress to apply the predictions of these in vitro systems to the in vivo situations of these diseases. The insights of research in the spondyloarthropathies may find broad applications in the rheumatic diseases.

Animals↗
PubMed1994

Mesalamine therapy in Reiter's syndrome.

A patient with chronic Reiter's syndrome (RS) refractory to nonsteroidal antiinflammatory therapy was prescribed mesalamine (Pentasa) therapy for a 4-month trial. Nine months after discontinuing therapy, mesalamine was reintroduced. A pre and posttreatment ileocolonoscopy with distal ileum biopsy was performed. Our patient responded well to mesalamine therapy as measured by improvement in joint count, morning stiffness, and fatigue. Symptoms returned after cessation of therapy. His RS once again went into remission after reintroduction of mesalamine. The pretreatment biopsy revealed inflammatory lesions usually described in the spondyloarthropathies. These lesions improved with resumption of mesalamine therapy.

Adult↗
PubMed1993

Occurrence of antibodies to Borrelia burgdorferi in patients with nonspirochetal subacute bacterial endocarditis.

OBJECTIVE: To determine the prevalence and specificity of antibodies to Borrelia burgdorferi in patients with nonspirochetal subacute bacterial endocarditis and assess whether increased levels of antibodies to B. burgdorferi were attributable to rheumatoid factor. DESIGN: Retrospective case-control study. SETTING: Urban referral center in an area devoid of infected ticks as a source of endocarditis sera. PATIENTS: Sera from 30 consecutive patients with culture-proven subacute endocarditis between 1979 and 1981 were compared with 30 control sera collected between 1989 and 1990. In addition, sera from 20 consecutive patients with rheumatoid arthritis who were positive for rheumatoid factor were collected between 1991 and 1992. Sera were compared with a convenience sample from 15 patients who met the criteria for Lyme disease. MEASUREMENTS: Antibodies to B. burgdorferi were assessed by enzyme-linked immunosorbent assay (ELISA) and immunoblot analysis. IgM rheumatoid factor was quantified using solid-phase radioimmunoassay or latex agglutination techniques. RESULTS: Thirteen of 30 patients with endocarditis (43%) compared with 3 of 30 normal controls (10%) had increased levels of antibodies to B. burgdorferi (P < 0.01). Of these 13 patients, only 1 had an immunoblot consistent with previous infection. The others had nonspecific immunoblots: 5 showed isolated 60-kd reactivity; 1 patient had isolated 41-kd reactivity; and 6 had no bands of reactivity. Immunoblots of the 3 controls with increased antibodies showed only isolated 41-kd reactivity. Thus, the specificity of the B. burgdorferi antibody test in patients with endocarditis was only 60% (95% CI, 42% to 78%), compared with 90% (CI, 79% to 100%) in controls. No correlation was noted between IgM rheumatoid factor and antibodies to B. burgdorferi in patients with endocarditis (r = 0.2; P > 0.2). Only 1 of 20 patients with rheumatoid arthritis without known bacterial infections had antibodies to B. burgdorferi. CONCLUSIONS: Although a positive ELISA test for B. burgdorferi may be a "true positive," a positive serologic test alone does not ensure that the clinical problem is due to Lyme borreliosis. Cross-reactive antibodies to shared epitopes between B. burgdorferi and the endocarditis organism may account for the high false-positive results.

Antibodies, Bacterial↗
PubMed1992

HLA-B27 expression modulates gram-negative bacterial invasion into transfected L cells.

The mechanism by which HLA-B27 confers genetic susceptibility to the seronegative spondyloarthropathies ankylosing spondylitis, Reiter's syndrome, and reactive arthritis, is not well understood. The current concept of an extraarticular bacterial infection functioning as the triggering event in a genetically susceptible host suggests the possibility of direct microbial-MHC interaction. We have addressed the role of HLA-B27 in microbial-host cell interaction by examining invasion by putatively arthritogenic gram-negative bacteria. Target cells used were murine L cells transfected with HLA-B27, HLA-A3, HLA-A2, HLA B44, HLA B18, or pSV2neo vector alone. Relative to the pSV2neo control and the HLA-A3 transfectant, HLA-B27-transfected cells demonstrated a consistent decrease in invasion for each of the following pathogens: Salmonella typhimurium (45 +/- 2% decrease), Shigella sonnei (53 +/- 13% decrease), Shigella flexneri (45 +/- 5% decrease), and enteroinvasive Escherichia coli (57 +/- 8% decrease). This decrease was specific for the HLA B27-transfected L cells and was not observed in the other B allele transfectants. The decreased invasion in the HLA-B27 transfectants is not the result of either altered endogenous mouse class I expression as a result of human class I transfection or increased intracellular bacterial killing within the B27 transfectants. There was an inverse relationship between the amount of surface expression of HLA-B27, as measured by FACS, and the degree of invasion. Blocking of surface B27 Ag with anti-B27 mAb augmented bacterial invasion in the B27 transfectants. These studies demonstrate a novel bacterial-B27 interaction that may have relevance to the pathogenesis of B27-related arthritis.

Animals↗
PubMed1992

Immunoepidemiology of post-Salmonella reactive arthritis in a cohort of women.

Following a foodborne outbreak of Salmonella dysentery in a group of 79 women and 4 men, 6 individuals were found to have reactive arthritis (ReA). None of the affected individuals had the classical genetic marker HLA B27 although 2 of the 6 had CREG antigens. IgA antibodies to the lipopolysaccharide of the causative organism, Salmonella heidelberg, were found to be elevated in those patients with active ReA compared to those with inactive ReA or those who had dysentery but did not develop ReA. The lymphocyte proliferative response to both PHA and the whole S. heidelberg organism was impaired in the patients with ReA (active or inactive) compared with the non-ReA patient controls. In this predominantly female outbreak of Salmonellosis, the development of ReA lacked an association with HLA class I antigens commonly recognized.

Adult↗
PubMed1992

HLA-B27/microbial mimicry: an in vivo analysis.

The association between three major spondyloarthritic diseases, ankylosing spondylitis, Reiter's syndrome, and reactive arthritis, and the major histocompatibility complex (MHC) class 1 antigen HLA-B27 is well documented. The hypothesis of cross-reactivity between HLA-B27 and the antecedent infection-causing Gram-negative pathogens such as Salmonella, Shigella and Yersinia has been suggested by in vitro studies employing monoclonal antibodies. We have examined the possibility of such cross-reactivity in vivo using various rabbit immune sera and patient sera as the source of cross-reacting antibody. Mouse L cells were transfected with HLA-A3 or HLA-B27 and used as a source of antigen. Western blot analysis employing denatured antigen, FACS analysis employing native antigen and immunoprecipitation studies were undertaken to detect cross-reacting antibodies generated in vivo to HLA-B27 antigen. Antibodies generated in vivo by infection in patients or immunization in animals against arthritogenic bacteria did not demonstrate any cross-reactivity with HLA-B27 by any of the methods used. As defined by the humoral immune response, molecular mimicry appears unlikely to explain the role of B27 in the pathogenesis of reactive arthritis.

Antibodies, Bacterial↗
PubMed1992

The role of infection in chronic arthritis.

The hypothesis that in arthritis an infectious agent functions at least as a triggering factor, if not a perpetuating one, has inspired decades of clinical investigation. Increasingly these studies are using more sophisticated tools of molecular biology which are applied in microbiology, immunology and immunogenetics. In the spondyloarthropathies these newer techniques are defining the molecular bases for the interplay of microbial antigen and the MHC antigens. The clues to provocative antigens are still elusive, although the class II MHC susceptibility is becoming clarified. Both viral and mycobacterial antigens are being examined in rheumatoid arthritis, but definitive answers are still lacking.

Arthritis↗
PubMed1991

Residues of pentachlorophenol and other chlorinated contaminants in human tissues: analysis by electron capture gas chromatography and electron capture negative ion mass spectrometry.

Samples of human tissues including testes, kidneys, prostate glands, livers, and adipose tissues removed at autopsy were analyzed for pentachlorophenol (PCP) and nonachloro-2-phenoxyphenol (NCPP); the fat samples were also analyzed for other chlorinated contaminants. Electron capture gas chromatography was used to quantitate the residues after isolation and cleanup. Identity of the residues was confirmed by electron capture negative ion mass spectrometry. All tissues analyzed for PCP tested positive with a range from 0.007 ppm (microgram/g) in subcutaneous fat to 4.14 ppm in testis. Residues of NCPP were much lower, ranging from levels below the detection limit to 0.59 ppm in testis. The highest average residues, based on the lipid content of the tissue, of PCP (1.09 ppm) and of NCPP (0.19 ppm) were found in testis followed by kidney (0.95 ppm PCP), prostate (0.84 ppm PCP), and liver (0.59 ppm PCP). Residues of these chemicals in the adipose tissues were on the average about 40 times lower than the residues in the non-fatty tissues. Other chlorinated contaminants found in the subcutaneous fat included hexa-, hepta-, and octa-chlorodibenzo-p-dioxins at sub-ppb levels and DDE averaging 2.47 ppm.

Adipose Tissue↗
PubMed1991

Infectious etiology of rheumatoid arthritis.

The infectious etiology of rheumatoid arthritis has been a long-standing hypothesis and in recent years is being examined with greater sophistication and scientific rigor. Synovitis may result indirectly from infection by the deposition of circulating immune complexes, by molecular mimicry, by in situ antigen deposition, or by arthritogenic toxins. Of candidate pathogens, recent interest has focused on mycobacterial HSP, EBV, and parvovirus B19. There is circumstantial evidence to support a link between each of these microorganisms and RA but presently all fall short of definitive proof of causality. It is anticipated that clearer answers may be forthcoming on this perplexing and intriguing question with the application of molecular biologic techniques to the study of synovial tissues.

Animals↗
PubMed1991

Interplay of microbe and major histocompatibility complex: a family study.

We describe a 24-year-old man who developed reactive arthritis (ReA) after a dysenteric illness caused by Salmonella hadar. Serologic tests suggested recent exposure of family members to Salmonella. All members of the family were HLA-B27 positive, but no other family member developed acute ReA, although 2 of them had clinical evidence of previously existing B27 associated arthritis.

Adult↗
PubMed1991

Antigens, the gastrointestinal tract, and arthritis.

There are a variety of forms of arthritis that appear causally related to a primary process in the gastrointestinal tract. Resolving the normal immune response to gut-acquired antigens of microbial and dietary origin can guide our understanding of the protean manifestations of the interface of arthritis and enteritis.

Antibody Formation↗
PubMed1990

Substance P and arthritis: analysis of plasma and synovial fluid levels.

The uncadecapeptide substance P (SP), which is localized in peripheral and central terminals of afferent nerve fibers with polymodal nociceptors, has recently been implicated as having a neurogenic, inflammatory role in experimental arthritis. We used a radioimmunoassay to measure SP levels in plasma and synovial fluid samples from patients with rheumatoid arthritis (RA), osteoarthritis (OA), Reiter's syndrome (RS), and posttraumatic arthritis, as well as in plasma samples from 13 normal subjects. Plasma SP levels in RS patients exceeded levels in RA and OA patients, which in turn exceeded levels in posttrauma patients and in normal subjects. Synovial fluid SP levels exceeded respective plasma levels for all groups, except in RS patients, in whom the plasma level was not significantly different from that in synovial fluid. SP levels in synovial fluid of RA, OA, and RS patients did not differ significantly from each other, but the level in posttrauma patients was higher than in all other groups (P less than 0.005). These studies demonstrate localized intraarticular SP release, and significant plasma/synovial fluid SP concentration gradients in several forms of arthritis.

Arthritis↗
PubMed1990

Autoantibodies to the HLA-B27 sequence cross-react with the hypothetical peptide from the arthritis-associated Shigella plasmid.

We previously reported elevated serum antibody levels to a peptide representing the HLA-B27 polymorphic region (B27 peptide) in HLA-B27(+) ankylosing spondylitis (AS) patients. A plasmid (pHS-2) isolated from arthritogenic Shigella flexneri strains had been shown to encode an amino acid sequence homologous to HLA-B27. Rabbit antibody to this sequence (pHS-2 peptide) strongly cross-reacted with B27 peptide and, to a much lesser extent, with Klebsiella nitrogenase peptide. Serum antibody levels to pHS-2 peptide were studied in 160 spondylarthropathy patients. 12 of 115 (10.4%) AS patients, 2 of 45 (4.4%) patients with Reiter's syndrome or reactive arthritis as well as 6 of 147 (4.1%) normal controls were shown to have elevated anti-pHS-2 peptide antibodies. Antibody levels to B27 and pHS-2 peptides were significantly correlated in 134 HLA-B27(+) patients (r = 0.333, P less than 0.001). 13 of 15 affinity-purified anti-B27 peptide antibodies from patients strongly cross-reacted with pHS-2 peptide, whereas only 3 weakly cross-reacted to nitrogenase peptide. Leucine appeared to be a critical residue for this cross-reaction. AS patients' anti-B27 peptide antibodies reacted with HLA-B27 transfected L cells. These results may suggest that pHS-2 peptide more efficiently "mimics" B27 peptide than does nitrogenase peptide. Involvement of pHS-2 in pathogenesis of spondylarthropathy through molecular mimicry mechanisms requires further study.

Amino Acid Sequence↗