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Biomedical subjects

A A Harrison

Publications and source records attributed to A A Harrison.

31 records · Page 2Linked to original sources

Inflammatory arthritis: imaging of endothelial cell activation with an indium-111-labeled F(ab')2 fragment of anti-E-selectin monoclonal antibody.

PURPOSE: To use imaging performed with an indium-111-labeled F(ab')2 fragment of monoclonal antibody that recognizes E-selectin (1.2B6) to evaluate inflammation. MATERIALS AND METHODS: After the in vivo immunoreactivity of In-111-F(ab')2 was verified, imaging experiments were conducted on pigs with induced arthritis of the right knee. In-111-labeled 1.2B6-F(ab')2, technetium-99m-hexamethylpropyleneamine oxime-labeled polymorphonuclear leukocytes (PMNs), and iodine-125-MOPC 21-labeled F(ab')2 (the control) were administered by means of intravenous injection. Scintigrams were obtained until 20 hours after injection, and tissue sampling was performed. RESULTS: Scintigrams showed uptake of 1.2B6 in the right knee but only faint filling of the joint space with PMNs. The right knee-to-left knee ratios on images obtained 20 hours after injection of the tracers were 10.8 +/- 3.6 for 1.2B6 and 1.1 +/- 0.4 for PMNs (P < .05). CONCLUSION: Endothelial cell immunotargeting with a radiolabeled anti-E-selectin F(ab')2 monoclonal antibody is feasible for use in imaging of inflammation.

Animals↗

Noninvasive imaging of E-selectin expression by activated endothelium in urate crystal-induced arthritis.

OBJECTIVE: To assess the expression of the cytokine-inducible endothelial leukocyte adhesion molecule E-selectin during the evolution of urate crystal-induced arthritis, using a recently described radiolabeled monoclonal antibody (MAb) imaging technique. METHODS: Monosodium urate (MSU) crystals and saline alone were injected respectively into the right (inflamed) and left (control) knees of 3 young pigs. Four hours later, 111In-labeled 1.2B6 F(ab')2 (anti-E-selectin MAb) and 125I-labeled MOPC 21 F(ab')2 (control MAb) were injected intravenously. Uptake of 1.2B6 in inflamed and control joints was assessed by scintigraphy 7 and 24 hours after intraarticular injection of MSU crystals. Immunohistochemistry studies and radioactivity counting of tissues were performed postmortem to confirm the observations from scintigraphy. RESULTS: MAb 1.2B6 F(ab')2 scintigraphic images of the knees revealed a significantly increased uptake in the right (inflamed) knee at 7 and 24 hours postinjection, particularly over the joint space. These in vivo images were consistent with E-selectin expression in the inflamed tissue detected by immunohistochemistry and with radioactivity counts postmortem. The synovial localization ratio (inflamed:control synovium counts) was 25.4 +/- 9.7 (mean +/- SD) for the anti-E-selectin MAb compared with 2.5 +/- 0.9 for the control MAb (P < 0.05, by paired Student's t-test). CONCLUSION: E-selectin is expressed by synovial endothelium during the evolution of urate crystal-induced arthritis and can be detected noninvasively using a radiolabeled MAb. This E-selectin imaging technique has considerable potential for the noninvasive assessment of endothelial activation in arthritis and other inflammatory rheumatic diseases.

Animals↗

Crew systems: integrating human and technical subsystems for the exploration of space.

Space exploration missions will require combining human and technical subsystems into overall "crew systems" capable of performing under the rigorous conditions of outer space. This report describes substantive and conceptual relationships among humans, intelligent machines, and communication systems, and explores how these components may be combined to complement and strengthen one another. We identify key research issues in the combination of humans and technology and examine the role of individual differences, group processes, and environmental conditions. We conclude that a crew system is, in effect, a social cyborg, a living system consisting of multiple individuals whose capabilities are extended by advanced technology.

Cybernetics↗

Immunoassay of platelet-derived growth factor in the blood of patients with diabetes mellitus.

Platelet-derived growth factor (PDGF) is a powerful mitogen for many cell types, and is believed to play a major role in wound healing when released from platelets at sites of injury. In diabetes mellitus, it has been proposed that premature release of PDGF from platelets impairs the ability of platelets to initiate healing, and also accelerates the development of diabetic complications such as angiopathy by increasing plasma-borne PDGF. However, plasma samples from diabetic patients have not previously been assayed for PDGF using suitable techniques. A sensitive monoclonal enzyme-linked immunoassay for PDGF was applied to plasma and serum samples from 18 healthy control subjects and 60 diabetic patients. Neither plasma nor serum PDGF concentrations differed significantly between control subjects, insulin-dependent, and non-insulin-dependent diabetic patients. However, 23% of the diabetic subjects had serum PDGF levels above the control range. Limited joint mobility, which is characterised by joint contractures and collagen deposition in the skin, and is associated with microvascular disease, was used as a marker of diabetic complications. Limited joint mobility affected 43% of the diabetic subjects. Patients with moderate limited joint mobility had had diabetes significantly longer than those without limited joint mobility (means 17 years and 9 years, respectively, p = 0.008). However, limited joint mobility was not associated with elevated serum or plasma PDGF in insulin-dependent or non-insulin-dependent diabetes. We conclude that complications of diabetes are unlikely to be caused by changes in systemic levels of PDGF.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Imaging vascular endothelial activation: an approach using radiolabeled monoclonal antibodies against the endothelial cell adhesion molecule E-selectin.

UNLABELLED: E-selectin is an endothelial cell-specific adhesion molecule for leukocytes expressed on the luminal surface of vascular endothelium during inflammatory responses. Because E-selectin expression is dependent upon ongoing stimulation by cytokines, this molecule offers a potentially useful target for imaging tissues in disease states involving cytokine-mediated endothelial cell activation. METHOD: To assess the imaging potential of an anti-E-selectin monoclonal antibody (Mab) 1.2B6, the accumulation of intravenously injected 111In-labeled Mab 1.2B6 was compared to that of 111In-control antibody in a model of arthritis in the pig. Injection of phytohaemagglutinin (PHA) into a knee led to E-selectin expression on vessels in the synovium and draining deep inguinal lymph nodes, as demonstrated by immunohistology. No E-selectin expression was seen in the control knee injected with buffer alone. Animals were given 111In-Mab 1.2B6 or 111In-control antibody intravenously 3 hr after the intra-articular injection of PHA. Radiolabeled antibody uptake was measured by direct counting of tissues 25 hr postmortem. RESULTS: The accumulation of radiolabeled control IgG in synovium and draining deep inguinal lymph nodes of PHA-injected knees was significantly higher than accumulation in tissues injected with buffer alone; however, the comparable ratios in animals receiving radiolabeled Mab 1.2B6 were significantly greater. Scintigraphy performed 24 hr after 111In-Mab 1.2B6 injection showed obvious localization of activity in the inflamed knee in each of three animals. CONCLUSION: Radiolabeled anti-E-selectin Mab can be used to image localized inflammatory tissues. This approach may be useful for investigating activated endothelium in human disease.

Animals↗

Evidence for a dissociation between benzodiazepine withdrawal signs.

The relationship between benzodiazepine-withdrawal induced weight loss and conditioned taste aversion was studied. Rats were treated with chlordiazepoxide (CDP) for 10 days (n = 37) or with vehicle (n = 39). Significant withdrawal-induced weight loss was observed. On day 11 all animals received an intra-oral infusion of saccharin. In a subsequent saccharin vs water choice test significant withdrawal-induced conditioned taste aversion was observed, as CDP pretreated animals drank less saccharin than controls. The two withdrawal indices were not correlated in the CDP pretreated animals [r = + 0.05], despite the fact that we studied a large group of rats. These data are in agreement with suggestions that drug withdrawal syndromes may be heterogeneous phenomena with a number of different underlying neural mechanisms.

Animals↗

The human experience in Antarctica: applications to life in space.

The increasing prominence of polar, spaceflight, and subaquatic environments has renewed interest in understanding human performance under conditions of isolation and confinement. In 1987, the National Aeronautics and Space Administration and the National Science Foundation co-sponsored a conference intended to revitalize behavioral research in such settings, and to explore the use of Antarctica as a behavioral laboratory for outer space. The present paper reviews recent research on men and women in isolation and confinement, with special reference to the proceedings of the NASA/NSF conference. The literature reviewed, which focuses on living systems and cuts across the individual, small group, organization, and community levels, suggests that researchers have become more systems-oriented, and have broadened their perspectives to encompass missions' larger temporal and social contexts. Among the topics reviewed are states of consciousness, stress, health, small group dynamics, personnel selection, crew training, and environmental engineering. Methodological and logistical problems are discussed, and the review concludes with recommendations for agencies that sponsor groups in isolation and confinement and for researchers who seek to study such groups.

Adaptation, Psychological↗

Standing out from the crowd: personalization of graduation attire.

During 1982 and 1983 college commencement ceremonies, a tally was made of students who displayed personal adornment in addition to their traditional academic garb. Degree conferred, sex of recipient, and year of graduation were related to the frequency and forms (political and nonpolitical) of adornment. Bachelor of Arts candidates were more likely to be adorned than were Bachelor of Science candidates, women were more likely to be adorned than were men, and 1982 graduates were more likely to be adorned than were 1983 graduates. The wearing of antinuclear protest ribbons varied as a function of degree but not as a function of sex, and the wearing of nonpolitical forms of adornment varied as a function of sex but not as a function of degree. Results indicate that personalization of graduation attire follows patterns reported in studies of secular dress and adornment. This correspondence between everyday and ritual clothing expressions suggests that the graduation ceremony may be a useful microcosm for future field studies of adolescents' attitudes and social differentiation.

Adolescent↗

Human factors in spacecraft design.

This paper describes some of the salient implications of evolving mission parameters for spacecraft design. Among the requirements for future spacecraft are new, higher standards of living, increased support of human productivity, and greater accommodation of physical and cultural variability. Design issues include volumetric allowances, architecture and layouts, closed life support systems, health maintenance systems, recreational facilities, automation, privacy, and decor. An understanding of behavioral responses to design elements is a precondition for critical design decisions. Human factors research results must be taken into account early in the course of the design process.

Environment Design↗