The susceptibility to type II collagen (CII)-induced arthritis (CIA) in mice is profoundly influenced by major histocompatibility complex (MHC) class II genes in the H-2 region. Analyses of MHC-congenic strains on the B10 background show that only strains developing an anti-CII antibody response after immunization with autologous CII develop arthritis after induction with CII from various species. The susceptible haplotypes have been found to be H-2q, H-2r, H-2w3 and H-2w17. In addition, these haplotypes respond to different patterns of CII derived from various species suggesting that T cell receptors and CII peptides interact. In contrast, certain haplotypes closely related to H-2q, such as the H-2p and H-2w5 haplotypes, are resistant to induction of CIA and are nonresponders to CII. We have earlier shown that a critical structure on the I-A beta molecule determines the susceptibility differences between the p and q haplotypes. We have now determined the structure of exon 2 of the A beta as well as some of the A alpha genes of the remaining haplotypes in the p, q and r families. The sequences show similarities between the CIA-susceptible haplotypes in the A beta C-terminal part and the A alpha N-terminal part of the first domains forming a large part of the antigenic peptide-binding site. Among the wild mouse-derived haplotypes, the w5 haplotype showed an A beta sequence identical to that of the p haplotype consistent with its nonresponder nature to CII immunization. These findings suggest that (a) structures shared between different class II molecules are of importance for the susceptibility to disease in mouse strains and (b) most likely recognition of different CII peptides is important for development of disease.

Amino Acid Sequence↗

PubMed1990

Comparison of flagellum and sonicate antigens for serological diagnosis of Lyme borreliosis.

A sonicate antigen and two concentrations of a purified flagellum antigen of Borrelia burgdorferi were compared for serological diagnosis of Lyme borreliosis by an enzyme immunoassay (EIA). Generally, the higher concentration of flagellum antigen was found to be superior to the lower concentration, which was diluted eight times compared to the higher concentration. The diagnostic sensitivity for IgG antibody detection increased from 13% in the sonicate EIA to 31% in the best flagellum EIA assay (p = 0.01) in sera from patients with erythema migrans (n = 70), and from 34% to 55% (p = 0.01) in sera from patients with neuroborreliosis (n = 77). However, the sensitivity for IgG in sera from patients with acrodermatitis chronica atrophicans (n = 20) was high in both assays: 90% in the sonicate EIA compared to 95% in the flagellum EIA. Regarding IgM, there was no significant difference between the sensitivity of the assays in sera from any of the patient groups. The sensitivity values for IgM and IgG in cerebrospinal fluid (CSF) from patients with neuroborreliosis were also without significant differences. Sera and CSF from patients with meningitis/encephalitis of non-Borrelia etiology (n = 35), multiple sclerosis (n = 9) or syphilis (n = 24), served as controls. The flagellum EIA showed a significantly improved specificity for IgG in CSF from controls with syphilis (p less than 0.01). It is concluded that purified Borrelia burgdorferi flagellum antigen is superior to a sonicate antigen, especially for serodiagnosis of the early stages of Lyme borreliosis.

Acrodermatitis↗

PubMed1990

Mortality trends for leukemia in selected countries.

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Adolescent↗

PubMed1990

Cultivation and characterization of spirochetes from cerebrospinal fluid of patients with Lyme borreliosis.

Attempts were made to culture spirochetes from cerebrospinal fluid samples of 105 patients suspected of having Lyme borreliosis with neurological complications. At the final evaluation, only 38 patients fulfilled the criteria of neuroborreliosis. Spirochetes were cultured from cerebrospinal fluid samples of four of these patients. All four patients had pleocytosis in their cerebrospinal fluid and a history of neurological symptoms of only 4 to 10 days in duration. Two of them had no detectable antibodies against any of the isolated spirochetes in their cerebrospinal fluid, both when tested with an enzyme-linked immunosorbent assay and when tested by immunoblotting. An antibody reaction against the homologous isolate that was distinctly stronger than that against the heterologous isolates was found in the serum and cerebrospinal fluid samples from one patient. The cells of the isolates were morphologically similar and showed a very similar protein pattern when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Cells of all isolates reacted with the monoclonal antibodies H5332 and H9724, which also react with Borrelia burgdorferi B31, the type strain. One isolate lost a major protein of 23 kilodaltons after subcultivation for 4 months. We conclude that isolation of spirochetes from cerebrospinal fluid might prove successful in clinically selected cases of Lyme borreliosis.

Adult↗

PubMed1990

Western immunoblot and flagellum enzyme-linked immunosorbent assay for serodiagnosis of Lyme borreliosis.

Western immunoblot with a whole-cell lysate was compared with an enzyme-linked immunosorbent assay with a purified flagellum antigen of Borrelia burgdorferi for serodiagnosis of Lyme borreliosis. The assays showed similar sensitivities and specificities in detecting immunoglobulin M and/or immunoglobulin G antibodies in sera from 68 patients with neuroborreliosis and 44 controls with meningitis and encephalitis or with multiple sclerosis. Flagellum enzyme-linked immunosorbent assay is more easily standardized and seems to be a more suitable diagnostic test in a routine laboratory.

Antibodies, Bacterial↗

PubMed1990

Aspects of the diagnosis of Lyme borreliosis.

Attempts were made to culture spirochetes from the cerebrospinal fluid of 105 patients with suspected Lyme borreliosis with neurological complications. At the final evaluation, only 38 patients fulfilled the criteria of neuroborreliosis. Spirochetes were cultured from the cerebrospinal fluid of four of these patients. All four had pleocytosis in their cerebrospinal fluid and a history of neurological symptoms of only four to ten days. Two had no detectable antibodies in their cerebrospinal fluid against any of the isolated spirochetes, neither when tested with an ELISA nor by Western blot. A distinctly stronger antibody reaction to the homologous isolate than to the heterologous isolates was found in serum and cerebrospinal fluid from one patient. The cells of the isolates were morphologically similar and showed a very similar protein pattern when analyzed by SDS-PAGE. Cells of all isolates reacted with the monoclonal antibodies H5332 and H9724, which also react with Borrelia burgdorferi isolate B31, the type species. One isolate lost a major protein of 23 kD after subcultivation for four months. We conclude that isolation of spirochetes from cerebrospinal fluid is not suitable as a routine method but might prove successful in clinically selected cases of Lyme borreliosis. The patient antibody response to spirochetal components was analyzed with Western blot. Antibodies to low-molecular components including a major protein with a molecular weight of 21-23 kD, and to a 41-kD major flagellar protein, were the first to appear in serum and in CSF samples. No single band in the immunoblots was found to be specific. By requiring a 41 kD band together with at least one low-molecular band for a positive immunoblot, 53 of 68 (78%) patients with neuroborreliosis had positive IgM and/or IgG serum immunoblots by visual reading of coded material. Western blot was more sensitive than ELISA based on a sonicate antigen which identified 40 of the 68 (59%) patient samples as positive, but not significantly more sensitive than ELISA based on a purified flagellum antigen which identified 50 of 68 (74%). Western blot tended to be more sensitive than the flagellum ELISA regarding sera from patients with neurological symptoms of 2 weeks or shorter duration. However, there was a tendency towards a lower specificity regarding the serological diagnosis of current Lyme borreliosis by Western blot than by sonicate and flagellum ELISAs.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1989

Evidence for two different classes of redox-active cysteines in ribonucleotide reductase of Escherichia coli.

The large subunit of ribonucleotide reductase from Escherichia coli contains redox-active cysteine residues. In separate experiments, five conserved and 2 nonconserved cysteine residues were substituted with alanines by oligonucleotide-directed mutagenesis. The activities of the mutant proteins were determined in the presence of three different reductants: thioredoxin, glutaredoxin, or dithiothreitol. The results indicate two different classes of redox-active cysteines in ribonucleotide reductase: 1) C-terminal Cys-754 and Cys-759 responsible for the interaction with thioredoxin and glutaredoxin; and 2) Cys-225 and Cys-439 located at the nucleotide-binding site. Our classification of redox-active cysteines differs from the location of the active site cysteines in E. coli ribonucleotide reductase suggested previously (Lin, A.-N. I., Ashley, G. W., and Stubbe, J. (1987) Biochemistry 26, 6905-6909).

Allosteric Site↗

PubMed1989

Search for KL--> pi 0 gamma gamma.

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Journal Article↗

PubMed1989

Comparison of Western blot and enzyme-linked immunosorbent assay for diagnosis of Lyme borreliosis.

The usefulness of Western blot in the serological diagnosis of Lyme borreliosis was evaluated compared with an ELISA using a whole cell sonicate antigen. Fifty-three of 68 (78%) patients with neuroborreliosis had positive IgM and/or IgG immunoblots and 40 of 68 (59%) had positive IgM and/or IgG ELISA titers in serum. Eight of 44 (18%) controls with meningitis/encephalitis of non-borrelia etiology had positive IgM and/or IgG immunoblots and 4 of 44 (9%) had positive IgM and/or IgG ELISA titers in serum. Western blot was more sensitive than ELISA, the difference being most pronounced in sera from patients with neurological disease for four weeks or less. Both patients and controls lived in an area endemic for Lyme borreliosis and some ELISA negative but Western blot positive controls were thought to have been previously exposed to Borrelia burgdorferi. However, the specificity for current disease was not improved by Western blot. In conclusion, Western blot does not seem to be the method of choice for screening purposes in a routine laboratory but can be used as a complement to ELISA for serodiagnosis in patients with disease of short duration.

Adolescent↗

PubMed1989

Clothing fasteners for long-term-care patients: evaluation of standard closures and prototypes on test garments.

For the elderly long-term-care patient it is of great psychological and practical importance to be able to dress and undress without assistance. However, the design and position of clothing fasteners often lead to a restriction of the functional capacity of the patient. The aim of this study was to facilitate a more independent daily life for long-term care patients. New fasteners were developed in accordance with a user-oriented product development process where a detailed knowledge of the final users and their capacity and limitations, problems, needs and wishes form the basis for further development. In an initial experimental study (I) the practical use of different standard clothing fasteners (button, hook and eye, nylon pressure tape and zipper) was evaluated. Different fasteners and positions are favourable to different patient groups. Wrist angle in different hand positions is crucial for the function of fasteners for persons with reduced hand function. User demands on clothing fasteners were specified and prototypes developed. In a subsequent study (II) an adapted oval button and a 'finger strap' alternative to hook-and-eye were designed and evaluated, together with a standard button. The oval button in combination with a vertical buttonhole improved the function for most patients, and the front position for the fasteners was superior to a diagonal or lateral position on the chest. The finger strap was of advantage to patients with hemiplegia and joint complaints but was difficult for many of the subjects to understand, being a technical innovation.

Journal Article↗

PubMed1989

Localization of a critical restriction site on the I-A beta chain that determines susceptibility to collagen-induced arthritis in mice.

Type II collagen-induced arthritis (CIA) in mice is an autoimmune experimental model for rheumatoid arthritis. Susceptibility to CIA is associated with certain major histocompatibility complex class II haplotypes. The two very closely related haplotypes H-2q and H-2p differ in susceptibility to CIA. Only mice of H-2q (DBA/1, B10G strains) but not mice of H-2p-expressing strains (like strain B10P) develop CIA and an autoimmune response to type II collagen (CII) after immunization with CII. In contrast to H-2p, the H-2q haplotype does not express I-E molecules. The purpose of the present study was to identify, at the molecular level, the structures on major histocompatibility complex class II molecules determining susceptibility to CIA and CII responsiveness. We first excluded the possible suppressive involvement of Ep or Ap molecules by showing that F1 hybrids between H-2p and H-2q haplotype strains, expressing Ep and Ap, are responders to CII and fully susceptible to CIA. Secondly, because A alpha chains appear identical, we sequenced the A beta first-domain exons of p and q allotypes and found only four diverging amino acids in the predicted amino acid sequence. These variable residues were closely located at positions 85, 86, 88, and 89 at the end of the postulated alpha-helix, which is of importance for interactions with the antigenic peptide and the T-cell receptor. We suggest that this region is a critical major histocompatibility complex restriction site for CIA and CII responsiveness in H-2q mice as compared with H-2p mice. The CIA will now be an excellent autoimmune model for studies on interactions between autoantigenic peptide, autoreactive T cells, and a particular major histocompatibility complex molecule, as has been postulated to be the initial event also in rheumatoid arthritis.

Amino Acid Sequence↗

PubMed1989

Collagen induced arthritis as an experimental model for rheumatoid arthritis. Immunogenetics, pathogenesis and autoimmunity.

The type II collagen (CII) induced arthritis animal model (CIA) provides opportunities to study the nature of autoimmune reactions leading to arthritis and may be used as a model for rheumatoid arthritis (RA). Thus, in similarity with RA, the CIA model, when induced with autologous CII, shows a chronic and progressive disease course. The susceptibility to both RA and CIA are correlated to the expression of certain MHC class II allotype genes. In both diseases are autoantibodies to CII and rheumatoid factors produced. Immunohistopathology of affected joints show in both diseases a dominance of activated macrophages/fibroblasts with a significant infiltration of activated T cells and an infiltration of granulocytes. We do here suggest that both RA and CIA are dependent on a synergy between delayed type hypersensitivity and immune complex mediated inflammatory mechanisms and that CIA provides opportunities for studies of immunospecific reactions leading to arthritis.

Animals↗