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Biomedical subjects

L Rollins

Publications and source records attributed to L Rollins.

5 recordsLinked to original sources

A retrogen strategy for presentation of an intracellular tumor antigen as an exogenous antigen by dendritic cells induces potent antitumor T helper and CTL responses.

Induction of an effective antitumor response requires CD4+ helper T (Th) cells to recognize antigens on the same dendritic cells (DCs) that cross-present CTL antigens. Such cross-presentation is difficult to achieve by current tumor vaccine strategies. Here, we develop a novel "Retrogen" strategy for DCs to efficiently cross-present an intracellular tumor antigen, MAGE-3, to both MHC class I and MHC class II in a cognate manner. Specifically, the MAGE-3 gene was linked to a leader sequence at its NH2 terminus for secretion and to a cell-binding domain at its COOH terminus for receptor-mediated internalization. DCs transduced with the modified MAGE-3 gene produced and secreted MAGE-3 proteins, which were efficiently taken up by DCs via receptor-mediated internalization and presented as exogenous antigens to class I and class II molecules. Immunization of mice with the transduced DCs expressing the MAGE-3 fusion protein, termed "Retrogen" for its retrograde transport/internalization after secretion, efficiently induced all arms of the adaptive antitumor immune responses. Thus, this retrogen strategy of using a unifying mechanism for DCs to cross-present an intracellular tumor antigen in a cognate manner could be generally used to improve the efficacy of tumor vaccines and immunotherapies.

Animals↗

Induction of vigorous helper and cytotoxic T cell as well as B cell responses by dendritic cells expressing a modified antigen targeting receptor-mediated internalization pathway.

Efficient Ag presentation is essential to induce effective cellular and humoral immune responses. Thus, one central goal of current immunotherapy and vaccine development is to enhance Ag presentation to induce potent and broad immune responses. Here, a novel Ag presentation strategy is developed by transducing dendritic cells (DCs) to produce an Ag for presentation as an exogenous Ag to efficiently induce both humoral and cellular immunity. The principle of this strategy is illustrated by genetically modifying DCs to secrete a model hepatitis B virus Ag fused with a cell-binding domain and to process the fusion Ag as an exogenous Ag after receptor-mediated internalization for MHC class I and II presentation. Vigorous Ag-specific CD4(+) helper and CD8(+) cytotoxic T cell, as well as B cell, responses were induced by the transduced DCs in mouse models. Thus, this novel strategy uses a receptor-mediated internalization process to efficiently induce all arms of the adaptive immunity and may provide a powerful means to develop potent vaccines and immunotherapies.

Animals↗

Do obstetrical charts present a liability risk?

The practice of obstetrics is well-known as a medicolegal, high-risk profession. Poor charting is considered an area of serious deficiency for physicians and especially for obstetricians. We reviewed the charting practices of obstetricians in a level II community hospital. The traditional 1- and 5-minute Apgar scores were employed as the screening criteria. Apgar scores of 7 or lower at 5 minutes were used to identify charts considered vulnerable to litigious activity. Of 1437 deliveries, 115 charts with 5-minute Apgar scores of 7 or lower were reviewed. Traditional requirements for charting, eg, history and physical exams, admission notes and diagnoses were recorded fairly consistently. However, elements such as statements of judgment, autopsy reports, scalp pHs, and extended Apgar scores that would render a chart defensible were sorely lacking. Charting skills, not necessarily the quality of care, may render obstetricians medicolegally vulnerable.

Apgar Score↗

Tumors of the salivary glands.

In a series of 65 salivary gland tumors seen in patients over eight years, 86 per cent were seen in the parotid gland, fewer than 10 per cent were in the submandibular gland, and none were in the sublingual gland. The remaining tumors were in minor salivary glands. About one half of the patients were in the sixth decade of life. Over 80 per cent of the lesions were benign; 50 per cent were from 1.5 to 2.5 cm in diameter, and the average delay between discovery and removal was over two years. In only one patient was there facial nerve involvement.

Adolescent↗

In vivo transfer of an Escherichia coli enterotoxin plasmid possessing genes for drug resistance.

Experiments were conducted to study transfer of an enterotoxin (Ent) plasmid from a porcine enteropathogenic Escherichia coli to an E coli K12 strain in the intestine of newly weaned pigs. The Ent plasmid carried genes for resistance to tetracycline, streptomycin, and sulfonamides, thereby permitting a selection for tetracycline-resistant exconjugants in the feces of the pigs. In vivo transfer of the Ent plasmid was demonstrated to occur when the pigs were given large oral inocula of donor and recipient cultures, 1 hour apart. Differences in extent of transfer were not detected in pigs given antibiotic-free feed compared with littermates on feed containing oxytetracycline at 50 g/ton. In one experiment, tetracycline-resistant Ent- exconjugants were found which appeared to have received an R plasmid from an enteropathogenic type of E coli resident in the intestine.

Animals↗