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Biomedical subjects

J Quinn

Publications and source records attributed to J Quinn.

At least 19 recordsLinked to original sources

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

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

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

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

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

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

L-glutamine stimulates jejunal sodium and chloride absorption in pig rotavirus enteritis.

Rotavirus enteritis is the leading cause of diarrhea in infants worldwide. A research priority of the World Health Organization is to develop oral rehydration solutions containing amino acids or other additives that will stimulate intestinal absorption more efficiently than the current glucose-based oral rehydration solutions. Glutamine is the principal metabolic fuel of the small bowel and a putative stimulator of mucosal repair. This report describes the transport response to mucosal L-glutamine following intestinal injury caused by porcine rotavirus. Peak symptoms and mucosal damage were observed 2-7 days after oral rotavirus inoculation. In vitro transport studies of the maximally injured region, the midjejunum (80% reduction in lactase), surprisingly, showed transport responses to L-glutamine (30 mmol/L) and L-alanine (30 mmol/L) that were similar qualitatively and quantitatively to those observed in control tissue. Subsequent application of mucosal D-glucose (30 mmol/L) caused additional stimulation of electrogenic Na+ transport, but the response to glucose was blunted (P less than 0.05) in the infected tissues. Glutamine and alanine enhanced Na+ absorption to a similar degree (2-2.5 muEq.cm-2.h-1), but glutamine stimulated equal amounts of electrogenic and electroneutral NaCl absorption, whereas alanine had no significant effect on net Cl- flux. Glutamine is a potentially useful substrate for investigation in oral rehydration solutions for infant diarrhea.

Alanine

The surgical management of children with incompletely resected hepatic cancer is facilitated by intensive chemotherapy.

This prospective study was undertaken to evaluate the efficacy of continuous-infusion doxorubicin and cisplatin (CI-DOX/CPPD) for the treatment of children with incompletely resected hepatic cancer. Of the 46 evaluable patients, 32 had hepatoblastoma (70%) and 14 had hepatocellular carcinoma. Ten children had stage II tumors (microscopic residual), 25 were defined as stage III (gross residual), and 11 had distant metastasis (stage IV). Twelve patients underwent initial incomplete resection of their hepatic lesions and in the 34 others tumor biopsy specimens were obtained. Chemotherapy was administered and the majority of the children (70%) had an excellent clinical response with a decrease in both alpha-fetoprotein levels and measured tumor dimensions. The combination of CI-DOX/CPDD clearly facilitated surgical management, allowing for delayed hepatic resections in 20 of the 34 patients (59%) whose tumors were initially biopsied and considered to be unresectable. Overall survival in this study demonstrates a significant improvement in comparison to the historical controls. Twenty-one patients (46%) remain in complete clinical remission an average of 30 months following diagnosis (range, 17 to 40 months). The outcome of the children with hepatoblastoma was much better than those with hepatocellular carcinoma (63% v 17% survival). Survival of the 20 children who underwent delayed hepatic resections was not statistically different from the 12 patients whose hepatic tumors were removed at the initial laparotomy (41% v 58% survival). Although no obvious survival advantage was observed in those patients who underwent initial hepatic resections, there did appear to be an increased risk of postoperative complications in children whose tumors were resected following chemotherapy (8% v 25%).

Adolescent

Bone resorption by macrophage polykaryons of giant cell tumour of tendon sheath.

The antigenic phenotype, ultrastructure and bone resorbing ability of mononuclear and multinucleated giant cells of four giant cell tumour of tendon sheath (GCTTS) lesions was assessed. Both the giant cells and the mononuclear cells exhibited the antigenic phenotype of cells of the monocyte/macrophage lineage. The giant cells, unlike osteoclasts, did not respond morphologically to calcitonin and showed ultrastructural and immunophenotypic features of macrophage polykaryons. However, like osteoclasts, the giant cells showed direct evidence of resorption pit formation on bone slices. This indicates that the GCTTS is composed of cells of histiocytic differentiation with the giant and mononuclear cell components expressing a similar antigenic phenotype. Bone resorption by macrophage polykaryons shows that this is not a unique defining characteristic of osteoclasts. Qualitative differences in the degree and pattern of bone resorption by macrophage polykaryons distinguish it from that of osteoclasts and may underlie the clinical behaviour of osteolytic lesions.

Adult

Information requirements and sedation preferences of patients undergoing endoscopy of the upper gastrointestinal tract.

Patients' attitudes to sedation and their information needs before undergoing endoscopy were investigated using a questionnaire. One hundred and two patients completed the study; 32 had undergone endoscopy before. Sixty-six (94%) of the new patients and all follow-up patients knew why they were undergoing the procedure; 65 (93%) new and 28 (88%) follow-up patients understood how the procedure was carried out. Forty-one percent of the new and 25% of the follow-up patients wanted an information booklet about their disease and its management. Most patients chose to be sedated during the endoscopy. The proportion wishing to be sedated did not differ significantly between the new and follow-up patient groups. Sedation and information should be offered to all patients undergoing endoscopy.

Attitude to Health

Immunocytochemical analysis of human synovial lining cells: phenotypic relation to other marrow derived cells.

The antigenic phenotype of human synovial lining cells in normal and hyperplastic synovium intima was determined with a panel of monoclonal antibodies directed against a large number of well defined myeloid (macrophage/granulocyte associated) antigens. Synovial lining cells express numerous macrophage associated antigens, including CD11b (CR3), CD13, CD14, CD16 (FcRIII), CD18, CD32 (FcRII), CD45 (leucocyte common antigen), CD54 (ICAM-1), CD64 (FcRI), CD68, and CD71 (transferrin receptor). Few synovial lining cells expressed CD11a (LFA-1) and CD11c (p150,95). Subintimal macrophages expressed all the macrophage associated antigens which were present on synovial lining cells and, in addition, expressed CD15a, CD25 (interleukin-2 receptor), CD34, and CD35 (C3b receptor), none of which was present on synovial lining cells. Synovial lining cell expression of a wide range of macrophage antigens argues in favour of their marrow origin and membership of the mononuclear phagocyte system.

Aged

Use of monoclonal antibodies to recognise osteoclasts in routinely processed bone biopsy specimens.

In decalcified (5% nitric acid) and undecalcified (glycol-methacrylate or resin embedded) routinely processed bone specimens osteoclasts against resorbing surfaces were identified with monoclonal antibodies directed against leucocyte common antigen (LCA) (PD7/26, 2B11), CD68 (KP1), and gpIIIa (Y2/51) but not against HLA-DR (CR3/43 and Ta11B5). Mononuclear cells on resorbing surfaces and occasional mononuclear cells against or near resting surfaces showed a similar pattern of reactivity. This study shows that immunohistochemistry is a sensitive and useful technique for identifying osteoclasts in routinely processed bone specimens. It also suggests a role for mononuclear cells (possibly pre-osteoclasts) in bone resorption.

Antibodies, Monoclonal

New sites of cellular vitronectin receptor immunoreactivity detected with osteoclast-reacting monoclonal antibodies 13C2 and 23C6.

The immunohistochemical profile of osteoclast-reacting monoclonal antibodies, 13C2 and 23C6, known to detect the alpha-chain of the vitronectin receptor, is described. Both antibodies reacted with several cell types apart from osteoclasts including megakaryocytes, smooth muscle cells, endothelial cells, thyroid follicular epithelium, renal glomeruli and tubular epithelium, myoepithelial and epithelial cells in the breast and prostate, and both cytotrophoblast and syncytiotrophoblast. In addition, macrophage polykaryons, synovial lining cells, a small number of mononuclear cells in buffy coats, and a few macrophage-like cells in the stroma of various tissues were also stained. The epitopes recognized by these antibodies are thus not osteoclast-specific and are present on other cells of the mononuclear phagocyte system. The implications of these results for osteoclast ontogeny, the nature of the antigens described and the question of osteoclast-specific antibodies are discussed.

Antibodies, Monoclonal