Biomedical subjects

R F Anders

Publications and source records attributed to R F Anders.

12 recordsLinked to original sources

PubMed1979

Hybridoma antibody immunoassays for the detection of parasitic infection: development of a model system using a larval cestode infection in mice.

A prototype immunodiagnostic assay has been developed using chronic infection with the larval cestode, Mesocestoides corti, as a model system in mice. The assay is highly sensitive, it appears to be absolutely specific for M. corti infection, and is based on the inhibition of binding (by sera from infected mice) of a radiolabelled anti-M. corti hybridoma antibody to a crude M. corti antigen extract. The hybridoma antibody binds to living M. corti larvae and is an IgG1 protein. In large scale experiments no false positives were detected and the only M. corti-infected mice not detected by the assay were hypothymic nude (nu/nu) mice. Only limited success has been achieved in attempts to convert the assay to one not requiring parasite antigen and based on the inhibition of binding of radiolabelled anti-parasite hybridoma antibody and a large pool of anti-idiotype antiserum. Monoclonal antibodies derived from anti-parasite antibody-secreting hybridoma cell lines will be of particular use in the development of new, highly specific, immunodiagnostic reagents for the detection of parasite infection, exposure and disease.

Animals↗

PubMed1979

IgG1 hypergammaglobulinaemia in chronic parasitic infections in mice: evidence that the response reflects chronicity of antigen exposure.

The IgG1 molecules in the sera of IgG1 hypergammaglobulinaemic mice chronically infected with the larval cestode, Mesocestoides corti, are a heterogeneous population. Although antibodies to M. corti are present, the question of whether a minority or majority of the serum IgG1 molecules has anti-parasite reactivity remains open. The splenic PFC response to an intravenous injection of SRBC in M. corti-infected mice does not consist of an unusually high proportion of IgG1 anti-SRBC PFC. Moreover, the adoptive anti-DNP PFC response of spleen cells from M. corti-infected mice to DNP-M. corti is not biased towards IgG1 antibody production. Since IgG1 hypergammaglobulinaemia is seen in mice with chronic, "high-dose" infections, an attempt has been made to simulate chronic antigenic exposure with SRBC in uninfected mice. A split, high-dose regime of SRBC injections leads to a high number and high proportion of IgG1 anti-SRBC PFC in the spleen in three strains of mice. The results suggest that the extraordinarily high levels of IgG1 seen in the sera of mice chronically infected with the metazoa, M. corti and Nematospiroides dubius, reflect persistent, high-dose, "strong", T cell-dependent stimulation of the B cell system.

Animals↗

PubMed1978

Amyloid fibril proteins found in Papua New Guinean and other amyloidoses.

Recent studies have established that amyloid fibrils found in different clinical conditions differ in the nature of their constituent proteins. In primary amyloidosis and in amyloidosis associated with multiple myeloma or macroglobulinaemia the amyloid fibrils are usually largely composed of fragments of immunoglobulin light chains. In secondary amyloidosis, protein AA, a unique protein unrelated to immunoglobulins, is the major component of the fibrils. Other chemical types of amyloid have been described in primary medullary carcinoma of the thyroid and in senile cardiac amyloidosis. In Papua New Guinea amyloidosis is seen secondary to chronic infections such as leprosy and tuberculosis as well as in patients without an apparent predisposing disease. The amyloid proteins obtained from a representative range of Papua New Guinean patients have been characterised and in all cases examined the amyloid was found to be of the protein AA or secondary type. Current research into the pathogenesis of secondary amyloidosis centres on the mechanisms whereby protein AA is derived from the presumed precursor molecule, protein SAA, which is a normal acute-phase reactant.

Adult↗

PubMed1977

A high molecular weight serum protein is the carrier for amyloid-related protein SAA.

In the present study evidence is presented that SAA in serum complexes to a carrier protein with a molecular weight of 100,000-200,000 daltons, with mobility in the alpha-region on electrophoresis, and with a rather low normal serum concentration. The carrier protein is apparently not albumin. SAA isolated from the carrier protein has a molecular weight of 14,000 daltons and does not complex to any considerable extent with itself under neutral conditions.

Amyloid↗

PubMed1977

Identification in human placentae of antigenic activity related to the amyloid serum protein SAA.

Antigenic activity related to the amyloid serum protein SAA was observed in indirect immunofluorescence studies on human placental tissue. Positive staining with anti-SAA antisera was localized to the cytoplasm of cells scattered within the mesenchymal stroma, thought to be fibroblasts, and to foetal stem vessel endothelium and some individual fibrillar structures in villous stroma and perivascular tissue. This immunofluorescent staining was specifically inhibited by protein SAA. In contrast, no immunofluorescent staining was achieved using antisera to the amyloid protein AA. Absorption and immunodiffusion studies have further suggested that anti-SAA antisera may recognize in human placentae only a very limited number of the antigenic determinants present in protein SAA but not in the smaller protein AA. The results support previous observations that protein SAA-like antigenic material can be found in normal human tissue.

Amyloid↗

PubMed1977

Amyloid-related serum protein SAA from three animal species: comparison with human SAA.

The amyloid-relates serum protein SAA has been isolated by gel filtration in 10% formic acid from three animal species: mink, mouse, rabbit. Sera used in the isolation procedure were obtained from animals in which high concentrations of SAA had been induced by treatment with LPS. The isolated SAA proteins had a subunit size similar to that of human SAA, with m.w. values ranging from 10,000 to 11,700 (estimated by gel filtration in 6 M guanidine-HC1) or 12,400 to 15,000 (estimated by SDS-PAGE). The m.w. studies and amino acid sequence data indicated that SAA and the amyloid fibril protein AA in the mouse, and probably also the mink, are related in the same way as in man, the two proteins having common NH2-terminal amino acid sequences and SAA being extended by 20 to 40 residues at the COOH-terminal end of the molecule.

Alpha-Globulins↗

PubMed1976

Connective tissue origin of the amyloid-related protein SAA.

Protein SAA is a serum protein related to the major constituent of secondary amyloid fibrils, protein AA, and has been suggested to be a precursor of the amyloid protein AA. In the present study, the origin of SAA was investigated by studying human fetal tissues and cultured human fetal fibroblasts with the indirect immunofluorescence technique. Anti-SAA antibodies reacted strongly with cultured fibroblasts producing a fine fibrillary cytoplasmic staining and with extracellular fibrils in loose connective tissues and vessel walls. The reactions were specifically inhibited by absorption with degraded amyloid material, isolated protein AA, isolated protein SAA, and sera from patients with elevated levels of SAA. In contrast, no inhibition was seen with amyloid fibril material devoid of AA protein or by human sera in which SAA was not detectable by double-diffusion tests. These observations showed that SAA-like material is produced by fibroblasts and indicate that it is a normal constituent of developing extracellular connective tissue fibers.

Amyloid↗

PubMed1976

Amyloid-related serum protein SAA in endotoxin-induced amyloidosis of the mink.

The concentration of the amyloid AA-related serum protein (SAA) was markedly increased after endotoxin injections in mink, mouse, rabbit, and man. It was particularly studied during the development of endotoxin-induced amyloidosis of the mink. Protein SAA was markedly elevated in all mink 24 h after the first endotoxin injection but had fallen to relatively low levels before the onset of amyloidosis at about 4 wk. These results are consistent with SAA being a circulating precursor of the amyloid fibril protein, AA. However, both proteins may be derived by proteolysis from a common precursor.

Amyloid↗

PubMed1976

Coexistence of protein AA and immunoglobulin light-chain fragments in amyloid fibrils.

Coexistence of amyloid fibril protein AA and homogeneous immunoglobulin light-chain fragments was found in the isolated amyloid fibrils of two patients with amyloidosis secondary to rheumatoid arthritis. The light-chain amyloid fibril protein showed antigenic identity with a light-chain amyloid from a patient with primary amyloidosis, which was identified as the VlambdaIV subgroup by amino acid sequence analysis. In the amyloid fibrils isolated from another patient with primary amyloidosis there was a mixture of VlambdaIV and VlambdaV homogeneous immunoglobulin light chains. Thus, a mixture of protein AA had lambda light chains or two different types of homogeneous light chains may be found in the amyloid fibrils of some patients.

Amino Acid Sequence↗

PubMed1975

Association of amyloidosis with erythema nodosum leprosum reactions and recurrent neutrophil leucocytosis in leprosy.

Rectal biopsy in 190 inpatients at a leprosy hospital in the Highlands of Papua New Guinea disclosed 16 patients with secondary amyloidosis. This represented 20% of the patients who had had polar lepromatous leprosy (L.L.) for more than 2 years. Patients with amyloidosis characteristically had either a history of recurrent attacks of erythema nodosum leprosum (E.NH) reactions or chronic trophic ulcers. Levels of the serum component (protein SAA) antigenically related to the amyloid fibril protein AA were monitored, at varying intervals for three months, in lepromatous patients with E.N.L. reaction. The SAA levels rose during E.N.L. reactions in parallel with the neutrophil count. SAA occurred with greatest frequency among patients with LH, while most non-lepromatous patients with detectable SAA had chronic trophic ulcers. The correlation between raised neutrophil count and elevated SAA concentration, observed in this and other studies, suggests that neutrophils are associated with the production of SAA.

Amyloidosis↗

PubMed1975

Isolation and characterization of amyloid-related serum protein SAA as a low molecular weight protein.

With direct immunoprecipitation or gel filtration under dissociating conditions, amyloid-related serum protein SAA has been isolated as a low molecular weight protein from the serum of two patients with rheumatoid arthritis but without known amyloidosis. The isolated protein SAA showed antigenic identity and an amino acid composition that was similar, but not identical, with isolated fibril protein AA. Molecular weight estimations suggest that protein SAA is approximately 50% larger than protein AA and has a molecular weight of 14,000-15,000 daltons. Preliminary results indicate that protein SAA from a patient with amyloidosis has a similar small molecular weight subunit.

Adolescent↗

PubMedDate not supplied

Secondary amyloidosis and the serum amyloid precursor in leprosy: geographical variation and association with leukocytosis.

The prevalence of the amyloid-related serum component, protein SAA, was investigated in two groups of leprosy patients from different areas of Papua New Guinea. Protein SAA was more prevalent in coastal leprosy patients (49% positive) than in highland patients (21% positive). Paradoxically, many more cases of amyloidosis were diagnosed in the highland group (17 of 199) than in the coastal group (3 of 112). In the highland patient group, SAA was found to correlate with the leprosy disease spectrum, being more prevalent in patients toward the lepromatous pole. Borderline and tuberculoid patients who had detectable SAA usually had neurotrophic ulcers. No such relationships were observed in the coastal patient group, probably because other infections, more common on the coast, were also responsible for causing increased concentrations of SAA which is known to behave as an acute phase reactant. A correlation was observed between SAA positivity and neutrophil leukocytosis. This suggests that various inflammatory stimuli such as erythema nodosum leprosum reactions, neurotrophic ulcers and intercurrent infections, all contribute to the prevalence of SAA in leprosy patients.

Amyloid↗