Abstract

The specialty of family medicine arose out of a combination of American public and professional concerns regarding fragmentation of health care and intended to preserve a type of physician with a scope of clinical competence that would allow the patient, not the disease, to be the focus. Family physicians serve as the patient's personal physician and provide entry to the health care system, provide comprehensive care, maintain continuing responsibility for the patient including necessary coordination of care and referral, and provide care appropriate to the patient's physical, emotional, and social needs in the context of family and community. Family medicine holds a key role in undergraduate medical education. The increasing emphasis on ambulatory training is due to shorter hospital stays (average of 5 days) and sicker patients being discharged home for outpatient follow-up. Third-year medical students (equivalent to the fifth-year medical students in Japan) rotate a mandatory six-week clinical clerkship, where they are expected to interview and examine ambulatory patients prior to the teaching physician. The hands-on experience of seeing ten to fifteen patients a day trains the students to gather pertinent data, establish rapport and therapeutic alliance, and counsel and educate patients on various preventive health and acute and chronic disease management issues. This is supplemented by lectures, grand rounds, resident morning reports and conferences, problembased learning, home visits, and community oriented primary care and preceptorships. The various learning strategies are implemented to approximate the real-life clinical setting and to enable the students to be independent, life-long learners. (Presented at the 1314th Meeting April 11, 2003.)

Dendritic cells are uniquely able to stimulate T cells and initiate immune responses against antigens that are not otherwise immunogenic. Thus, there is considerable interest in using dendritic cells for patient benefit, and trials of dendritic cell-based vaccines for cancer are in progress. One goal of these trials is to elicit cytotoxic lymphocyte (CTL) responses that target tumor cells. In most trials, tumor antigen-derived peptides are added to dendritic cells in vitro and cells are then administered to patients. In this approach, the HLA genotype of the patient and the specific tumor antigen-derived peptide that binds to the patient's MHC antigens must be known. Alternatively, dendritric cells can be loaded with tumor antigens by transfecting them with cDNAs that encode tumor antigens or by infecting them with viruses that express these proteins. Transfection of dendritic cells is not efficient and there are theoretical and practical issues that relate to the use of viruses. Recently, we have explored the use of bacterial recombinant proteins that bear protein transduction domains (PTDs) as components of dendritic cell-based cancer vaccines. PTDs are short stretches of positively charged amino acids that enable proteins that contain them to enter cells in an energy- and receptor-independent fashion. We have incorporated the HIV TAT protein PTD into proteins and demonstrated that these proteins transduce dendritic cells very efficiently. We have also demonstrated that transduction of mouse dendritic cells with recombinant PTD-containing antigens allows them to elicit cytotoxic T cell responses against non-self and self antigens. The CTL activity generated is sufficient to prevent engraftment of mice with tumors, and these vaccines have some therapeutic efficacy. This approach has some theoretical advantages over those that are in current use, and may be useful in patients. (Presented at the 1324th Meeting September 9, 2003.)

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