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Biomedical subjects

N Mulligan

Publications and source records attributed to N Mulligan.

7 recordsLinked to original sources
PubMed2001

Abnormal pulmonary granuloma formation in osteopontin-deficient mice.

Osteopontin is a novel cytokine that is expressed in pulmonary granulomatous disease such as sarcoidosis and tuberculosis. It can regulate macrophage and T cell migration, activation, and cytokine expression, yet its role in granuloma formation and evolution is unknown. We induced hypersensitivity pulmonary granulomas by embolizing Schistosoma mansoni eggs to the lungs of osteopontin-deficient (null mutant) mice and osteopontin-sufficient (wild-type control) mice. Granulomas from osteopontin-null animals were smaller at early time points and contained remarkably few macrophages and macrophage-derived epithelioid cells and giant cells. T cell accumulation was unaffected by osteopontin deficiency. These results demonstrate that osteopontin regulates macrophage accumulation during pulmonary granuloma formation, and may explain the impaired ability of osteopontin-deficient hosts to control mycobacterial disease.

Animals↗
PubMed1999

Osteopontin is associated with T cells in sarcoid granulomas and has T cell adhesive and cytokine-like properties in vitro.

Sarcoidosis is a systemic disease characterized by the accumulation of activated T cells and widespread granuloma formation. In addition, individual genetic predisposition appears to be important in this disease. Osteopontin, a noncollagenous matrix protein produced by macrophages and T lymphocytes, is expressed in the granulomas of tuberculosis, and is associated with genetic susceptibility to intracellular infection. The function of osteopontin in these T cell-mediated responses is unknown. We sought to elucidate the role of osteopontin in granulomatous inflammation by characterizing its expression in different stages of sarcoidosis and its effector function on T cells in vitro. Lymphocyte-associated expression of osteopontin in sarcoidosis was demonstrated by immunohistochemistry, and its expression correlated with granuloma maturity. In addition, osteopontin induced T cell chemotaxis, supported T cell adhesion (an effect enhanced by thrombin cleavage of osteopontin), and costimulated T cell proliferation. These results suggest a novel mechanism by which osteopontin and thrombin modulate T cell recruitment and activation in granulomatous inflammation.

Adult↗
PubMed1999

BCL-2 expression and inhibin-A in adrenal neoplasms: a comparative study.

Differential diagnosis between adrenal cortical and adrenal medullary lesions may be difficult in many cases. Different immunohistochemical, histochemical tools as well as ultrastructural diagnostic techniques have been employed to aid in differentiating between these lesions. Recently, both inhibin-A and BCL-2 have been shown to stain selectively adrenal cortical tissue and its derived neoplasms but not adrenal medulla or pheochromocytomas. In this study we compared the staining reactions of inhibin-A and BCL-2 in cases of adrenal cortical adenomas and carcinomas as well as pheochromocytomas. We found that both inhibin-A and BCL-2 stained cortical derived tissues, but not medullary derived tissues. Staining intensity for inhibin-A was significantly weaker than for BCL-2. We found that fixation techniques may influence the staining reactivity, as some cases did not immunoreact with any of the antibodies. We conclude that both inhibin-A, and, preferentially, BCL-2 are useful additions to a staining protocol to help in the differential diagnosis of cortical and medullary neoplasms.

Adenoma↗
PubMed1997

A new generation endovascular graft for repair of abdominal aortic aneurysms.

BACKGROUND: Several endovascular grafts are currently being evaluated for repair of abdominal aortic aneurysms (AAA). The goals of our study were twofold. First was to develop a new endovascular graft with several advantages over previous devices: (1) smaller size (16 fr), (2) recapturability (the device can be partially deployed and then recaptured and moved to a new location or entirely removed if needed), and (3) accuracy and ease of placement. Our second goal was to develop an animal model in which a full-scale prototype of the device could be tested. METHODS: Our final endovascular graft prototype was developed after extensive in-vitro testing, and trials of earlier prototypes in dog, pig, and female sheep models. Uncastrated male sheep, 75 to 100 kg, were chosen as the animal model in which to test the device. These animals had infrarenal aortas that were comparable to that of small humans, with diameters of 12 to 15 mm. Two models were used: (1) native infrarenal aorta, and (2) artificial infrarenal aneurysm. Pre-implant and postimplant angiography and intravascular ultrasound were used to evaluate graft placement, and were repeated prior to euthanasia and necropsy. RESULTS: The final prototype was implanted in 22 animals. Sixteen animals had the device placed in their native infrarenal aorta. Three animals were sacrificed immediately after implantation, and 6 more were euthanized after 2 weeks (n = 2), 6 weeks (n = 2), and 3 to 4 months (n = 2). In 7 animals the device is still in place. All procedures were successful. Pathology confirmed complete exclusion of the aorta and thrombosis of all lumbar branches covered by the graft. There was no evidence of graft malposition, migration, or perigraft leak, and no evidence of significant vessel injury on histology. Six animals had artificial aneurysms surgically created and then repaired with the device. A technical error resulted in a failure in 1 case; the remaining aneurysms were all successfully excluded. CONCLUSIONS: We report the development of a new endovascular prosthesis for the repair of AAA. Newer design features provide for smaller delivery size (16 fr), facilitate accurate placement, and provide the option when the device is partially deployed to recapture and reposition the device if necessary. In addition, we have developed an animal model in which this device, and future endovascular aortic devices, can be tested.

Animals↗
PubMed1991

Perceptual interference improves explicit memory but does not enhance data-driven processing.

Nairne (1988) has recently demonstrated that interfering with the perceptual processing of an item at study improves later memory for that item. Nairne hypothesized that interfering with perceptual processes induces a data-driven generation process that enhances the representation of visual information. Using a variant of Nairne's procedure, we both replicated his original findings and tested his hypothesis that enhanced data-driven processing causes the current effect. The results of studies using free recall and perceptual identification tests were inconsistent with Nairne's hypothesis. We consider several alternative interpretations in the General Discussion.

Adult↗