Use Of Therapeutic Interventions Research Articles

P21(WAF1/Cip1) retards the growth of human squamous cell carcinomas in vivo.

The excessive proliferation exhibited by cancer cells is frequently a result of their failure to adequately regulate cell cycle progression. In the present study, we developed a xenograft model of oral cancer in athymic mice, using squamous carcinoma cell lines and examined the ability of the cyclin-dependent kinase inhibitor p21 (WAF1/Cip1) to retard tumour growth in vivo, using a retroviral delivery system. Human p21 cDNA was cloned by polymerase chain reaction, expressed, and the encoded protein shown to have biological activity in in vitro kinase assays. Amphotropic retrovirus cultures which expressed recombinant p21 were generated and used to treat established squamous cell carcinoma xenografts. Two weeks following onset of treatment tumours injected with p21 virus producer cells showed a reduction in size between 3- and 10-fold compared with tumours which received control cells which produced control virus alone. The data indicate that recombinant p21 may be of future use for therapeutic intervention in oral cancer.

One step ahead of the game: viral immunomodulatory molecules.

For decades cell biologists have relied on viruses to facilitate the study of complex cellular function. More recently, the tragedy of the AIDS epidemic has focused considerable human and financial resources on both virology and immunology, resulting in the generation of new information relating these disciplines. As the miracle of the mammalian immune system unfolds in the laboratory, the elegance of the mechanisms used by co-evolving viruses to circumvent detection and destruction by the host becomes inescapably obvious. Although many observation of virus-induced phenomena that likely contribute to the virus's escape of immune surveillance are still empirical, many other such phenomena have now been defined at the molecular level and confirmed in in vivo models. Immune modulators encoded within viral genomes include proteins that regulate antigen presentation, function as cytokines or cytokine antagonists, inhibit apoptosis, and interrupt the complement cascade. The identification of such gene products and the elucidation of their function have substantially strengthened our understanding of specific virus-host interactions and, unexpectedly, have contributed to the recognition of potent synergy between viruses, which can result in an unpredictable exacerbation of disease in co-infected individuals. Because many viral immune modulators clearly have host counterparts, viruses provide a valuable method for studying normal immune mechanisms. It is conceivable that an improved understanding of virus-encoded immunomodulators will enhance our ability to design reagents for use in therapeutic intervention in disease and in vaccine development.

The Meaning of Sea Kayaking for Persons With Spinal Cord Injuries

Research has described benefits of physical, athletic, and avocational activity on improving self-esteem, quality of life, and locus of control in persons with disabilities. The objective of this study was to identify meaningful components of the experience of sea kayaking as described by persons with spinal cord injury (SCI). Three subjects with SCI who had participated in recreational kayaking were interviewed. Qualitative research methods included strategies from Guba's model for rigor in qualitative research, Spradley's interviewing guidelines, and Good's method of semantic network analysis. Three interviews of approximately 45 min in length were conducted with each subject. Initial interviews began with a single question: "Tell me about sea kayaking." Subsequent questions contained only concepts and terms used in the subjects' responses. The subjects valued the novelty, challenge, safety, sociability, and natural environment aspects of sea kayaking. Perceptions of the self as able in the eyes of others and the need for support in pursuit of outdoor leisure activities were themes that figured prominently in the subjects' discourse. Subjects' comments indicate that meaningful time use and the construction of an identity after injury are linked. This link has also been suggested in the rehabilitation literature. This information suggests the use of therapeutic intervention that supports a person's adjustment to an irreversible SCI.

Altered inflammatory responses in leukotriene-deficient mice.

Leukotrienes have been implicated in the regulation of immune responses, including inflammation and immediate hypersensitivity reactions. Here, we describe the phenotypic analysis of leukotriene-deficient mice generated by inactivation of the 5-lipoxygenase (5LO) gene. These 5LO(-/-) mice were unable to synthesize detectable levels of leukotrienes and were more resistant to lethal anaphylaxis induced by platelet-activating factor. The intensity of an acute inflammatory response induced by arachidonic acid was similar in 5LO(-/-) mice and controls. However, the response in 5LO(-/-) mice, but not in controls, could be virtually eliminated by a cyclooxygenase inhibitor. These data suggest that inflammatory responses are modulated by arachidonic acid metabolites through a variety of interconnected mechanisms. This has important implications for understanding the early events of an inflammatory response and for designing drugs for use in therapeutic intervention.

CYTOKINES AND INFLAMMATION IN CARTILAGE DEGRADATION

Since the discovery of humoral factors such as cytokines, which could modulate connective tissue metabolism, questions have arisen concerning their involvement in the pathophysiology of osteoarthritis. At least three cytokines, interleukin (IL-1), tumor necrosis factor, and interleukin-6, were identified in articular tissue and suggested to play a role during inflammation. Osteoarthritic chondrocytes have a higher sensitivity to stimulation by IL-1 with respect to metalloprotease production than normal chondrocytes that seem to be related to an increase in the level of IL-1 receptors. Natural antagonists capable of directly counteracting cytokine action on joint cells have been identified; however, their role in osteoarthritis remains to be determined, particularly in the context of their use for therapeutic intervention.

The use of therapeutic interventions to reduce crowding-related arousal: A preliminary investigation

Studies of mass transportation crowding have universally shown that such crowding is arousing and often anxiety producing. Attempts to intervene to reduce arousal and anxiety have met with mixed results. In this study four therapeutically based interventions were used to reduce the arousal evoked by a laboratory analogue of mass transportation crowding. Subjects in the intervention conditions showed significantly fewer increases in pulse rate during crowding. Two of the intervention conditions showed significant decreases in skin conductance level when compared to subjects in an uninstructed crowded condition. An intervention which increased feelings of control over the environment resulted in a more positive view of the environment but did not decrease physiological arousal any more than interventions which did not increase perceived control.