The epithelium that lines the gut is impermeable to macromolecules and microorganisms, except in Peyer's patches (PPs), where the lymphoid follicle-associated epithelium (FAE) contains M cells that transport antigens and microorganisms. A cultured system that reproduces the main characteristics of FAE and M cells was established by cultivation of PP lymphocytes with the differentiated human intestinal cell line Caco-2. Lymphocytes settled into the epithelial monolayer, inducing reorganization of the brush border and a temperature-dependent transport of particles and Vibrio cholerae. This model system could prove useful for intestinal physiology, vaccine research, and drug delivery studies.

This study describes the properties of a clone of immortalized cells (m-ICc12 cells) derived from the bases of small intestinal villi from 20-day-old fetuses of L-type pyruvate kinase (L-PK)/ TAg1 transgenic mice. The mice harbor the simian virus 40 large T antigen under the control of the 5' regulatory sequence from the L-PK gene. m-ICc12 cells expressed nuclear large T antigen, had a prolonged life span, and were nontumorigenic when injected into nude mice. They formed confluent monolayers of cuboid cells separated by tight junctions, developed dense, short apical microvilli, and formed domes. They also possessed cytokeratins, villin, aminopeptidase N, dipeptidyl-peptidase IV, and glucoamylase and retained crypt cell features, including intracellular sucrase isomaltase and alpha-L-fucose glycoconjugates accumulation and expression of the polymeric immunoglobulin receptor and the cystic fibrosis transmembrane conductance regulator gene. Thus the m-ICc12 cell line obtained by targeted oncogenesis in transgenic mice maintained in culture several important properties and differentiated functions of intestinal crypt cells.

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Objective. Pneumococcal vaccination is important for patients taking immunosuppressive medications, but prior studies suggest that most patients do not undergo vaccination. The aim of this study was to evaluate the effects of a point-of-care paper reminder form as a quality improvement (QI) strategy to increase the numbers of immunosuppressed patients being kept up-to-date with pneumococcal vaccination in a rheumatology practice.Methods. Selected rheumatologists at 5 ambulatory practice sites received a point-of-care paper reminder form to be applied to patients who were not up-to-date with pneumococcal vaccination. Interrupted time-series analyses were used to measure the effect of the intervention on the pneumococcal vaccination rates among patients, comparing the rates in the intervention group with those in a control group of rheumatologists who did not receive the intervention. Adjusted Cox proportional hazards models were examined to identify independent predictors of being up-to-date with pneumococcal vaccination.Results. We evaluated a total of 3,717 patients (66.0% with rheumatoid arthritis) who were taking immunosuppressive medications (74.1% women, mean age 53.7 years). Rheumatologists who received the intervention had a significant increase in the rate of patients who were up-to-date with pneumococcal vaccination, from 67.6% to 80.0% (P ‫؍‬ 0.006), in the time period following the intervention, compared to a rate that remained stable, from 52.3% to 52.0% (P ‫؍‬ 0.90), among patients in the nonintervention control group during this same time period. In regression models, positive predictors of being up-to-date with pneumococcal vaccination at the patient level included the following: having received the intervention (hazard ratio Conclusion. A QI strategy involving a simple point-of-care paper reminder form significantly increased the rate of being up-to-date with pneumococcal vaccination among patients receiving immunosuppressive medications in our rheumatology practices over a 6-month period.[

Receptive ano-rectal intercourse is a major cause of HIV infection in men having sex with men and in heterosexuals. Current knowledge of the mechanisms of entry and dissemination during HIV rectal transmission is scarce and does not allow the development of preventive strategies. We investigated the early steps of rectal infection in rhesus macaques inoculated with the pathogenic isolate SIVmac251 and necropsied four hours to nine days later. All macaques were positive for SIV. Control macaques inoculated with heat-inactivated virus were consistently negative for SIV. SIV DNA was detected in the rectum as early as four hours post infection by nested PCR for gag in many laser-microdissected samples of lymphoid aggregates and lamina propria but never in follicle-associated epithelium. Scarce SIV antigen positive cells were observed by immunohistofluorescence in the rectum, among intraepithelial and lamina propria cells as well as in clusters in lymphoid aggregates, four hours post infection and onwards. These cells were T cells and non-T cells that were not epithelial cells, CD68+ macrophages, DC-SIGN+ cells or fascin+ dendritic cells. DC-SIGN+ cells carried infectious virus. Detection of Env singly spliced mRNA in the mucosa by nested RT-PCR indicated ongoing viral replication. Strikingly, four hours post infection colic lymph nodes were also infected in all macaques as either SIV DNA or infectious virus was recovered. Rapid SIV entry and dissemination is consistent with trans-epithelial transport. Virions appear to cross the follicle-associated epithelium, and also the digestive epithelium. Viral replication could however be more efficient in lymphoid aggregates. The initial sequence of events differs from both vaginal and oral infections, which implies that prevention strategies for rectal transmission will have to be specific. Microbicides will need to protect both digestive and follicle-associated epithelia. Vaccines will need to induce immunity in lymph nodes as well as in the rectum.