Risk factors for cutaneous warts and the influence factors of curative effect of 5-flurouracil therapy in southern China.

BACKGROUND: To systematically explore the risk factors of cutaneous warts and influence factor for the effectiveness of 5-fluorouracil (5-FU). METHODS: This is a case-control study of 408 cutaneous warts patients and 408 controls of Chinese Han population in southern China. In addition, 244 patients who presented with an initial episode of warts without treatment were treated with intralesional 5-FU. The influence factors of 5-FU therapeutic effects were analyzed. RESULTS: After adjustment, we found age (≤14 years old), lower education attainment, alcohol intake, smoking, less daily sleeping hours, severe psychological stress, hyperhidrosis, living in house or apartment, having cutaneous warts roommates, and sharing personal items with other persons to be risk factors for warts. Importantly, physical fitness played a protective role against warts. Two hundred and twenty-seven patients in 244 (93.03%) were successfully treated with 5-FU. Multivariate analysis indicated that smoking, alcohol intake, severe psychological stress, more than six months' duration of cutaneous warts, lesions on foot and warts diameter ≥5 mm adversely affected the effectiveness of 5-FU. CONCLUSIONS: The newly identified risk factors for cutaneous warts and influence factors for efficacy of 5-FU provided clues for warts prevention and treatment of Chinese Han population.

Predictive Soft Tissue Airway Volume Analysis in Mandibular Distraction: Pushing The Envelope in Surgical Planning for Obstructive Sleep Apnea.

Three-dimensional computed tomography has been used in both preoperative planning of mandibular distraction osteogenesis and in the evaluation of postoperative resolution of tongue-based airway obstruction. The authors present a case report using software to predict postdistraction airway volume during virtual surgical planning (VSP) of mandibular distraction osteogenesis in a 7 year old. The predicted increase in airway volume derived from VSP was 33.57% (1716 mm(3) preoperatively to 2292 mm(3) postvirtual distraction). Based on the three-dimensional computed tomography, the actual airway volume increased to 2211 mm(3) postoperatively, a 28.85% increase.The implications of this advancing technology are far-reaching. An illustrative case is presented herein to demonstrate the efficacy of the airway prediction and its limitations. The authors believe that, with continued investigation, this novel approach may be a standard feature of all VSP sessions for the treatment of tongue-based airway obstruction.

Disruption of tight junctions and induction of proinflammatory cytokine responses in colonic epithelial cells by Campylobacter jejuni.

Campylobacter jejuni is a leading cause of human enterocolitis and is associated with postinfectious complications, including irritable bowel syndrome and Guillain-Barré syndrome. However, the pathogenesis of C. jejuni infection remains poorly understood. Paracellular pathways in intestinal epithelial cells are gated by intercellular junctions (tight junctions and adherens junctions), providing a functional barrier between luminal microbes and host immune cells in the lamina propria. Here we describe alterations in tight junctions in intestinal epithelial monolayers following C. jejuni infection. Apical infection of polarized T84 monolayers caused a time-dependent decrease in transepithelial electrical resistance (TER). Immunofluorescence microscopy revealed a redistribution of the tight junctional transmembrane protein occludin from an intercellular to an intracellular location. Subcellular fractionation using equilibrium sucrose density gradients demonstrated decreased hyperphosphorylated occludin in lipid rafts, Triton X-100-soluble fractions, and the Triton X-100-insoluble pellet following apical infection. Apical infection with C. jejuni also caused rapid activation of NF-kappaB and AP-1, phosphorylation of extracellular signal-regulated kinase, Jun N-terminal protein kinase, and p38 mitogen-activated protein kinases, and basolateral secretion of the CXC chemokine interleukin-8 (IL-8). Basolateral infection with C. jejuni caused a more rapid decrease in TER, comparable redistribution of tight-junction proteins, and secretion of more IL-8 than that seen with apical infection. These results suggest that compromised barrier function and increased chemokine expression contribute to the pathogenesis of C. jejuni-induced enterocolitis.

Protein kinase C signaling regulates ZO-1 translocation and increased paracellular flux of T84 colonocytes exposed to Clostridium difficile toxin A.

Clostridium difficile toxin A increases paracellular permeability in colonic epithelial T84 cells by mechanisms involving RhoA glucosylation and actin depolymerization. However, we previously observed that toxin A-mediated decline in transepithelial electrical resistance preceded changes in cell morphology and tight junction ultrastructure (Hecht, G., Pothoulakis, C., LaMont, J. T., and Madara, J. L. (1988) J. Clin. Invest. 82, 1516-1524). Recent studies also showed that C. difficile toxins induce early cellular responses, including activation of mitogen-activated protein kinases, generation of reactive oxygen metabolites, and calcium influx. The aim of this study was to investigate whether toxin A-induced early cellular responses contribute to the permeability changes. We found that toxin A stimulated the activities of membrane and cytosolic protein kinase Calpha (PKCalpha) and cytosolic PKCbeta. A specific PKCalpha/beta antagonist (myristoylated PKCalpha/beta peptide) blocked toxin A-mediated RhoA glucosylation. Furthermore, decreased transepithelial electrical resistance and increased translocation of ZO-1 from tight junction occurred within 2-3 h of toxin A exposure and were also inhibited by PKCalpha/beta antagonist. During this time period, toxin exposure did not induce translocation of ZO-2, dephosphorylation or translocation of occludin, or cell rounding. Our data indicate that PKC signaling regulates toxin A-mediated paracellular permeability changes and ZO-1 translocation.