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Biomedical subjects

A R Sanderson

Publications and source records attributed to A R Sanderson.

At least 19 recordsLinked to original sources
PubMed1997

Observer performance methodologies for evaluating blood vessel visibility in MR angiograms using accurate geometric registration to high resolution x-ray angiograms.

Receiver operator characteristic (ROC) and two alternative forced choice (2AFC) methodologies for quantitatively assessing vessel visibility in MR angiography (MRA) were examined using x-ray angiography images as truth. The methodologies required MRA projection images with the same orientation and magnification as the x-ray images. Geometric distortions limited the quality of the registration. The observer performance measurements were compared to vessel contrast-to-noise ratio (CNR) measurements. Receiver bandwidth (RBW) and magnetization transfer (MT) effects in 3D time-of-flight MRA were evaluated. Overall, applying MT significantly increased all three measurements while decreasing the RBW significantly improved the 2AFC and CNR measurements. The relative importance of both effects on the 2AFC measure increased as vessel diameter decreased, although statistical significance was limited by small samples for diameters less than approximately 0.7 mm. These results demonstrate the usefulness of these observer performance methodologies for MRA technique assessment.

Angiography, Digital Subtraction↗
PubMed1988

Cytomegalovirus and beta 2 microglobulin in urine specimens. Reciprocal interference in their detection is responsible for artifactually high levels of urinary beta 2 microglobulin in infected transplant recipients.

We have previously shown that the binding of host beta 2 microglobulin (beta 2 m) by cytomegalovirus (CMV) in body fluids masks the viral antigenic determinants preventing its detection by CMV-specific monoclonal antibodies. We now report that the recognition of CMV-bound beta 2m by anti-beta 2m-specific antibodies in assays for beta 2m, results in erroneously high readings for beta 2m levels in urine specimens containing CMV. Urinary beta 2m levels have previously been reported to be elevated in patients with CMV infection--however, when virion bound beta 2m was removed by ultracentrifugation of urine specimens, the levels of free beta 2m were not found to be elevated in these patients. Since CMV is frequently excreted by transplant recipients and acquired immunodeficiency syndrome patients, our data suggest that measurements of urinary beta 2m levels in such patients are unreliable unless the urine specimens are confirmed to be free of CMV before analysis.

Animals↗
PubMed1987

Acquisition of HLA class I W6/32 defined antigenic determinant by heavy chains from different species following association with bovine beta 2-microglobulin.

Murine, rat, rabbit and guinea pig class I heavy chains, which do not react with W6/32 monoclonal antibody when they are expressed in association with autologous beta 2-microglobulin (beta 2-m), can acquire such a reactivity once they are expressed at the surface of cells cultured in conditions which allow their association with bovine beta 2-m. Sequence comparison of beta 2-ms suggests that glutamine at position 89 might be critical for the induction of the W6/32 defined antigenic determinant. However, in the murine species, certain class I heavy chains, in spite of their association with bovine beta 2-m, do not express this determinant. Using genetically engineered hybrid class I molecules and selected congenic strains of mice this negative property was shown to be related to the presence of a cysteine residue at position 121 which allows covalent association of beta 2-m to class I heavy chains (Bushkin, Y., J-S. Tung, A. Pinter, J. Michaelson, and E. A. Boyse. 1986. Unusual association of beta 2-microglobulin with certain class I heavy chains of the murine major histocompatibility complex. Proc. Natl. Acad. Sci. USA 83:432). Therefore, expression of the W6/32 defined antigenic determinant implicates both the beta 2-m and the second domain of the heavy chain, but its expression (or exposure) is prevented by the covalent fixation on cysteine 121 of the light chain.

Animals↗
PubMed1987

Antigenic determinants shared between HLA-A, -B, -C antigens and H-2 class I molecules modified by bovine beta-2 microglobulin.

The specificity of the mouse class I-specific antibody COB6-3 was examined in detail. It was found to react with the mouse class I molecules H-2Db, Kd, and Qa-2, and with human HLA-A, -B, -C antigens. The specificity pattern of COB6-3, despite its different origin, was similar to that of the monomorphic HLA class I-specific antibody W6/32. Cross-inhibition studies show that on human cells the antigenic determinants recognized by the two antibodies are situated close together and may be identical. On mouse cells, reactivity of both antibodies was generated upon replacement of mouse beta-2 microglobulin (B2m) with its bovine counterpart, but differences in specificity were observed using human B2m.

Animals↗
PubMed1987

Beta 2 microglobulin enhances the infectivity of cytomegalovirus and when bound to the virus enables class I HLA molecules to be used as a virus receptor.

We have previously demonstrated that human cytomegalovirus (CMV) binds the host protein beta 2 microglobulin (beta 2m) from body fluids or from cell culture media. In this report we have examined the effect of the beta 2m on viral infectivity. We have shown that the addition of human purified beta 2m, or a fraction of foetal calf serum corresponding to bovine beta 2m, to culture medium increased the amount of infectious extracellular CMV, compared to that from cells grown in serum-free medium. Metabolic labelling experiments demonstrated that this effect was not due to an increase in the amount of extracellular virus but to an increase in the infectivity of the virus present in extracellular fluids. We concluded that the binding of beta 2m by CMV increased its infectivity. We have shown that CMV and beta 2m compete for binding sites on fibroblasts. As the main binding site on cells for beta 2m is the class I HLA heavy chain we compared the binding of CMV to the Raji and Daudi cell lines which express or lack expression of class I HLA molecules. The binding of radiolabelled beta 2m-coated CMV was significantly higher to Raji cells than to Daudi cells. Furthermore, CMV could compete with beta 2m for binding to Raji cells, although the reverse was not true. These results demonstrate that CMV can use class I HLA molecules as a virus receptor. We propose that when coated with beta 2m, CMV has the capacity to displace beta 2m from the class I HLA heavy chain-beta 2m dimer on the cell surface and bind to cells. The fact that beta 2m enhances infectivity suggests that such binding leads to productive infection of cells.

Cell Line↗
PubMed1985

Exploitation of phylogenetic distance in cell surface immune labeling: studies with beta 2-microglobulin.

Beta 2-microglobulin (beta 2M) is part of the HLA molecule, and is found on the cell surface of human nucleated cells. In certain skin tumors, malignant change has been associated with a loss of this surface beta 2M, indicating a possible diagnostic value for this marker. At present beta 2M is best identified in paraffin-embedded tissue by means of a triple-layer peroxidase-antiperoxidase technique, using mammalian polyclonal antisera. Recently a polyclonal antiserum against human beta 2M has been produced in chickens. Because of the phylogenetic differences between the species, the resulting antiserum is likely to recognize more epitopes on the beta 2M and show greater sensitivity than antisera raised in mammalian species. To confirm this hypothesis, the avian antiserum was compared to both mammalian polyclonal (rabbit) and monoclonal (mouse) antibody in vitro. beta 2M fixed to plastic surfaces combined with more avian than mammalian antibody. Furthermore, insolubilized chicken antibody could bind more secondary antibody-horseradish peroxidase conjugate than could insolubilized mammalian antibody, thus showing even greater enhancement with this system. Immunohistochemical analysis of these systems confirmed that the chicken strategy has greater sensitivity, and can be used in an indirect system with consequent reduction in nonspecific background activity. It is the most suitable technique for the investigation of the distribution of beta 2M in paraffin-embedded tissue.

Animals↗
PubMed1983

Associated peptides isolated from human seminal fluid containing beta 2-microglobulin determinants.

Proteins in human semen that react with a monoclonal mouse antibody to human beta 2-microglobulin (h beta 2M) have been isolated using immunoaffinity chromatography. As well as material of the same size as h beta 2M, a peptide of approximately 18000 kdaltons was isolated. It is suggested that this substance either contains h beta 2-M sequences itself or, as is more likely, is non-covalently associated with an h beta 2M-like peptide chain.

Animals↗
PubMed1983

Absence of human leukocyte antigen molecules in skin tumors and some cutaneous appendages: evidence using monoclonal antibodies.

Four highly sensitive monoclonal antibodies were assessed for their use in an immunoperoxidase technic on cutaneous sections. Three, B2, C23, and 2A1, were found to discriminate basal cell carcinomas (BCCs) from benign proliferative disorders of skin, and 2A1, a monoclonal antibody against the heavy chain component of class 1 human leukocyte antigens (HLA) for the first time directly demonstrated the absence of this structure from the malignant cell membrane. However, the deeper portions of hair follicles were also found to be unlabeled, and further study of benign follicular tumors which may histologically mimic basal cell carcinomas is suggested.

Antibodies, Monoclonal↗
PubMed1981

Interspecies exchange of beta 2-microglobulin and associated MHC and differentiation antigens.

Radiolabeled human beta 2-microglobulin (beta 2m) can bind to mouse histocompatibility (H-2) antigens on the cell surface or to partially purified H-2 antigens in solution. The complexes containing human beta 2m and H-2 antigens from C3H (H-2k) mice could be immunoprecipitated specifically with alloantisera, rabbit anti-H-2 xenoantisera, and with monoclonal H-2-specific antibodies. Specific association with H-2 antigens was also observed with other haplotypes. The only exception was B10.D2 (H-2d) from which complexes containing human beta 2m could only be precipitated with anti-H-2-xenosera. Thus radiolabeled human beta 2m can be used as a specific label for mouse H-2 antigens in precipitation and radioimmunoassays. The application of this finding extends to major histocompatibility complex antigens of other species, and to differentiation antigens with primary association with beta 2m.

Animals↗
PubMed1981

Antigen-specific helper factor reacts with antibodies to human beta 2 microglobulin.

Antigen-specific helper factor was induced in vitro from lymphoid cells of monkeys and mice by using an antigen derived from Streptococcus mutans. Helper activity was removed from supernatants of monkey cells by affinity chromatography on Sepharose 4B insolubilized antibodies specific for human beta 2-microglobulin (H beta 2M) prepared in chicken, rabbit and rat, and an insolubilized monoclonal mouse anti-H beta 2M antibody-bound monkey helper factor activity. However, guinea pig antibody to human beta 2M was inactive. In parallel studies, the pattern of absorption of mouse helper factor (HF) was different from that of the monkey in that insolubilized guinea pig anti-H beta 2M bound helper factor, whereas rabbit and monoclonal anti-H beta 2M failed to do so. Although these findings were not compatible with an intact beta 2M chain being present in helper factor, they may imply a cross-reactivity of beta 2M with a "constant region" of helper factor that may share common sequences with beta 2M. This may suggest that factor genes have evolved from the same ancestral genes as beta 2M.

Animals↗
PubMed1981

Epitope sites on human beta 2-microglobulin identified by xenogeneic polyclonal and monoclonal antisera.

The relationship between the ability to produce insoluble antigen--antibody complexes from a polypeptide antigen, beta 2-microglobulin and specific antisera from several different species has been examined. The size of complexes was determined by gel-filtration chromatography using serum, immunoglobulin, and divalent F(ab')2 or monovalent Fab fragments therefrom. Non-precipitating primate antihuman beta 2-microglobulin sera recognized two epitopes on the antigen and monoclonal antibody only one epitope, whereas precipitating antisera recognized three or more epitopes, as lattice theory predicts. The paucity of epitope sites reaffirms the unusual immunogenicity of human beta 2-microglobulin when presented to certain primates in the form of an HLA antigen.

Antibodies, Monoclonal↗
PubMed1981

An antigenic determinant of human beta 2-microglobulin masked by the association with HLA heavy chains at the cell surface: analysis using monoclonal antibodies.

Four anti-human beta 2-microglobulin monoclonal antibodies were produced against whole lymphoid cells or against urinary beta 2-microglobulin. Their reactivity was fully inhibited by purified soluble beta 2-microglobulin. The B1.1G6, C23.24.2, and B2.62.2 antibodies bound either to free or to HLA-complexed beta 2m. They recognized the same or very close determinants, since they achieved mutual blocking. In contrast, the C21.48A1 antibody did not bind to the cell surface and did not recognize the same determinant on the purified beta 2-microglobulin molecule as the others. It was able to bind and to form a specific complex with membrane beta 2-microglobulin only, once separated from the HLA heavy chain. These data strongly suggest that the C21.48A1 antigenic determinant might be hidden when the beta 2-microglobulin is complexed with the HLA heavy chains at the cell surface.

Antibodies, Monoclonal↗
PubMed1980

Preparation of a defined immune complex for use in C1q binding assays.

Soluble immune complexes of human beta 2 microglobulin with its IgG antibodies from Macaca irus antisera have been tested for suitability as a reference preparation for immune complex assays in human disease. The defined complex described is stable on storage, behaves reproducibly in a C1q solid phase binding assay and fulfills the criteria required for an international reference standard.

Animals↗