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Biomedical subjects

Roger Luo

Publications and source records attributed to Roger Luo.

5 recordsLinked to original sources

Distinct and separable roles of the complement system in factor H-deficient bone marrow chimeric mice with immune complex disease.

Plasma complement factor H (Cfh) is a potent complement regulator, whereas Cfh on the surface of rodent platelets is responsible for immune complex processing. For dissection between the two, bone marrow chimeras between Cfh-deficient (Cfh(-/-)) and wild-type C57BL/6 mice were created. Platelet Cfh protein was tracked with the Cfh status of the bone marrow donor, indicating that platelet Cfh is of intrinsic origin. In an active model of immune complex disease, Cfh(-/-) mice that were reconstituted with wild-type bone marrow had levels of platelet-associated immune complexes comparable to those of wild-type mice and were protected against the excessive glomerular deposition of immune complexes seen in Cfh(-/-) mice, yet these mice still developed glomerular inflammation. In contrast, wild-type mice with Cfh(-/-) bone marrow had reduced platelet-associated immune complexes and extensive glomerular deposition of complement-activating immune complexes, but they did not develop glomerular pathology. The large quantities of glomerular C3 in wild-type mice with Cfh(-/-) bone marrow were in the form of iC3b and C3dg, whereas active C3b remained in Cfh(-/-) recipients of wild-type bone marrow. These data show that plasma Cfh limits complement activation in the circulation and other accessible sites such as the glomerulus, whereas platelet Cfh is responsible for immune complex processing.

Animals↗

Dasatinib (BMS-354825) inhibits KITD816V, an imatinib-resistant activating mutation that triggers neoplastic growth in most patients with systemic mastocytosis.

Mastocytosis is associated with an activating mutation in the KIT oncoprotein (KITD816V) that results in autophosphorylation of the KIT receptor in a ligand-independent manner. This mutation is inherently resistant to imatinib and, to date, there remains no effective curative therapy for systemic mastocytosis associated with KITD816V. Dasatinib (BMS-354825) is a novel orally bioavailable SRC/ABL inhibitor that has activity against multiple imatinib-resistant BCR-ABL isoforms in vitro that is presently showing considerable promise in early-phase clinical trials of chronic myeloid leukemia (CML). Pharmacokinetic analysis suggests that high nanomolar concentrations of dasatinib can be achieved safely in humans. In this study, we demonstrate significant inhibitory activity of dasatinib against both wild-type KIT and the KITD816V mutation in the nanomolar range in in vitro and cell-based kinase assays. Additionally, dasatinib leads to growth inhibition of a KITD816V-harboring human masto-cytosis cell line. Significantly, dasatinib selectively kills primary neoplastic bone marrow mast cells from patients with systemic mastocytosis while sparing other hematopoietic cells. Computer modeling suggests that the KITD816V mutation destabilizes the inactive conformation of the KIT activation loop to which imatinib binds, but it is not predicted to impair binding of KIT by dasatinib. Based upon our results, further evaluation of dasatinib for the treatment of systemic masto-cytosis in clinical trials is warranted. Moreover, dasatinib may be of clinical utility in other disease settings driven by activating KIT mutations.

Animals↗

Cognitive human factors for telemedicine systems.

The recent integration of telephony systems with information and communication technology (ICT) enables the development of innovative tools for telemedicine. The dissemination and widespread acceptance of telephone-based care monitoring systems challenge the researcher to deal with the cognitive factors involved in the patient-physician interaction, and the way they should be to shape up the technological solutions. This paper proposes a model that describes the impact of socio-cognitive factors in the complex process of health care management. The model has been used to design and develop a telephone system for the management of hypertensive patient within the EU funded Homey project. The knowledge existed in a widely accepted guideline for the care of hypertension has been represented and augmented through the proposed cognitive model. The final product is an intelligent system able to manage an adaptive dialogue. It monitors patients' adherence and increases their involvement by promoting self-care through frequent virtual visits, which is complementary to the traditional face-to-face encounters with their primary care physicians.

Artificial Intelligence↗

Cost-effectiveness of preventive occupational therapy for independent-living older adults.

OBJECTIVES: To evaluate the cost-effectiveness of a 9-month preventive occupational therapy (OT) program in the Well-Elderly Study: a randomized trial in independent-living older adults that found significant health, function, and quality of life benefits attributable to preventive OT. DESIGN: A randomized trial. SETTING: Two government-subsidized apartment complexes. PARTICIPANTS: One hundred sixty-three culturally diverse volunteers aged 60 and older. INTERVENTION: An OT group, a social activity group (active control), and a nontreatment group (passive control). MEASUREMENTS: Use of healthcare services was determined by telephone interview during and after the treatment phase. A conversion algorithm was applied to the RAND 36-item Short Form Health Survey to derive a preference-based health-related quality of life index, quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio for preventive OT relative to the combined control group. RESULTS: Costs for the 9-month OT program averaged $548 per subject. Postintervention healthcare costs were lower for the OT group ($967) than for the active control group ($1,726), the passive control group ($3,334), or a combination of the control groups ($2,593). The quality of life index showed a 4.5% QALY differential (OT vs combined control), P <.001. The cost per QALY estimates for the OT group was $10,666 (95% confidence interval = $6,747-$25,430). For the passive and active control groups, the corresponding costs per QALY were $13,784 and $7,820, respectively. CONCLUSION: In this study, preventive OT demonstrated cost-effectiveness in conjunction with a trend toward decreased medical expenditures.

Activities of Daily Living↗