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Biomedical subjects

J Quinn

Publications and source records attributed to J Quinn.

At least 109 records · Page 6Linked to original sources
PubMed1993

Lipoylated and unlipoylated domains of human PDC-E2 as autoantigens in primary biliary cirrhosis: significance of lipoate attachment.

Approximately 95% of patients with primary biliary cirrhosis have antimitochondrial antibodies against the E2 component of the pyruvate dehydrogenase complex (E2p). Immunodominant sites on E2p have been localized to the inner lipoyl domain, which serves as a covalent attachment site for the essential cofactor, lipoic acid. However, it is not clear whether the presence of lipoic acid is necessary for autoimmune recognition of human E2p. To facilitate further studies on the inner lipoyl domain and to assess the importance of lipoic acid in antibody binding, we used the previously cloned human E2p cDNA in the construction and high-level expression in Escherichia coli of a subgene encoding the domain. Purification and analysis of the gene product revealed that both lipoylated and unlipoylated forms of the intact domain are generated. Immunoblotting, enzyme-linked immunosorbent assay inhibition experiments and antibody affinity measurements using isolated lipoylated and unlipoylated domains demonstrated that the presence of the lipoyl residue is crucial for effective recognition by primary biliary cirrhosis patients' autoantibodies, which have a higher relative affinity for the lipoylated form. Contrary to some previous suggestions, these results indicate that antibodies in primary biliary cirrhosis patients' sera bind most effectively to a unique peptide-cofactor conformation in the lipoyl domain of the human E2p polypeptide. Moreover, the availability of large amounts of human lipoyl domain will permit further studies into the role of the antigen (if any) in disease pathogenesis.

Acetyltransferases↗
PubMed1992

The properties of total adducts and interstrand crosslinks in the DNA of cells treated with CB 1954. Exceptional frequency and stability of the crosslink.

CB 1954 (5-(aziridin-1-yl)-2,4-dinitrobenzamide) becomes, upon bioactivation, a difunctional alkylating agent. It can be up to a 100,000-fold more cytotoxic in cells that are able to bioactivate it than in those that cannot. This increase in cytotoxicity is much greater than would be predicted from the conversion of a monofunctional alkylating agent to a difunctional one. We now show that the interstrand crosslink formed in the DNA of CB 1954-sensitive cells has some unusual properties. In Walker cells, which are able to activate CB 1954, the interstrand crosslink is the major adduct and can constitute up to 70% of the total adducts. These crosslinks are only poorly excised, as are those produced in V79 cells (which are themselves unable to activate CB 1954) by co-culturing them with Walker cells. Also, CB 1954 is approximately 10-fold more reactive toward the DNA of Walker cells than V79 cells. These observations may explain the extent of the increase in cytotoxicity accompanying the bioactivation of CB 1954.

Animals↗
PubMed1992

Novel antigenic determinant expressed in neurons of the dorsolateral hypothalamus in rat and human.

Previous studies have identified a group of cells in the dorsolateral hypothalamus that project to many different areas in the CNS, such as thalamus, diagonal band of Broca, basal ganglia, cerebral cortex, hippocampus, and olfactory bulb. Their role is presently unknown, but the cells have been reported to stain for an intriguing array of putative neurotransmitter-related substances, including alpha-melanocyte-stimulating hormone (alpha MSH), melanin-concentrating hormone (MCH), human growth-hormone-releasing factor 1-37 (hGRF 1-37), corticotropin-releasing factor (CRF), metorphamide, and acetylcholine esterase. A monoclonal antibody produced in the present study, alpha C11, stains both the cell bodies of this system in hypothalamus, with a punctate pattern, and varicose fibers in the various target areas. In double-label immunocytochemical experiments in rat DLH, alpha C11 and MCH staining exactly overlaps. Concentrations of alpha MSH and MCH high enough to completely block staining with the corresponding antisera had no effect on staining with alpha C11. Similarly, CRF, hGRF 1-37, and metorphamide were unable to block alpha C11 staining. The results suggest that the antigenic epitope for alpha C11 is not contained in alpha MSH, MCH, CRF, hGRF, or metorphamide, and thus, that alpha C11 is detecting another antigen uniquely expressed in these neurons. The punctate appearance of staining in the hypothalamus and the concentration of staining in fiber varicosities suggests that the alpha C11 epitope may be involved in synaptic function.

Acetylcholinesterase↗
PubMed1992

Case management in rural areas. Definition, clients, financing, staffing, and service delivery issues.

How does case management in rural areas differ from that in urban areas? How does the informal system of family, church, neighbors, and volunteers affect case management in rural areas? What are the strengths and problems of rural case management? The authors report the attitudes of rural case managers and attendees at a conference sponsored by two homecare organizations to these and other questions related to rural case management.

Aged↗
PubMed1992

Suicide and community psychiatric care--a preliminary report.

A preliminary survey of 34 suicides among patients attending community services for the chronically mentally ill revealed a rate of 520 per 100,000 admitted. In contrast to earlier hospital surveys, no risk variables were identified for patients dying by suicide. Thirty-four percent of suicides occurred within one week of the last treatment and 59% within 3 months of service entry. It appears that early and intensive follow-up may be necessary to prevent suicide among patients receiving community psychiatric care.

Adult↗
PubMed1992

Resorption of bone by inflammatory cells derived from the joint capsule of hip arthroplasties.

The role of inflammatory cells in aseptic loosening and failure of cemented joint replacements is unclear. Inflammatory cells from the revision joint capsule of four failed hip arthroplasties were examined to determine their nature and resorptive capacity. The capsules contained numerous macrophages and abundant foreign-body macrophage polykaryons, distinguished from osteoclasts by their antigenic phenotype and lack of response to calcitonin. When cultured on cortical bone slices in vitro, both macrophages and macrophage polykaryons produced small resorption pits and were associated with areas of superficial resorption of the bone surface. These results indicate that foreign-body induced macrophages and macrophage polykaryons are capable of a type of low-grade bone resorption which may be of pathogenic significance in the loosening of cemented joint prosthetic components.

Antibodies, Monoclonal↗
PubMed1992

Polymethylmethacrylate-induced inflammatory macrophages resorb bone.

Macrophages and their fused products are commonly found at the polymethylmethacrylate cement-bone interface, but it is not known if they contribute directly to the osteolysis associated with loosening of the cemented prosthesis. We isolated mononuclear phagocytes from granulomas formed by subcutaneous implantation of polymethylmethacrylate into mice and incubated them on bone slices in which they formed resorption lacunae after co-culture for seven to 14 days with both marrow stromal cells and osteoblast-like cells (in the presence of 1 alpha,25-dihydroxyvitamin D3 and dexamethasone). Increased numbers of tartrate-resistant acid phosphatase-positive mononuclear and multinucleated cells formed in these cultures. Both in the presence and absence of stromal cells, macrophages produced extensive superficial roughening of the bone surface. Polymethylmethacrylate-induced macrophages are thus capable of low-grade surface and high-grade lacunar osteolysis, the latter requiring the presence of specific hormonal and stromal cell elements. These two forms of bone resorption could account for the pathogenesis and clinical patterns associated with loosening of the cemented prosthesis.

Animals↗