Human hair follicle dermal sheath and papilla cells support keratinocyte growth in monolayer coculture.

Traditional skin grafting techniques are effective but limited methods of skin replacement. Autologous transplantation of rapidly cultured keratinocytes is successful for epidermal regeneration, but the current gold-standard technique requires mouse fibroblast feeders and serum-rich media, with serum-free systems and dermal fibroblast (DF) feeders performing relatively poorly. Here, we investigated the capacity of human hair follicle dermal cells to act as alternative supports for keratinocyte growth. Dermal papilla (DP) dermal sheath (DS), DF and 3T3 cells were used as inactivated feeder cells for human keratinocyte coculture. Under conditions favouring dermal cells, proliferation of keratinocytes in the presence of either DS or DP cells was significantly enhanced compared with DF cells, at levels comparable to keratinocytes cultured under gold-standard conditions. Secreted protein acidic and rich in cysteine (SPARC) expression increased DS and DP cells relative to DFs; however, further experiments did not demonstrate a role in keratinocyte support.

Preoperative evaluation of pancreatic cystic lesions: cost-benefit analysis and proposed management algorithm.

BACKGROUND: This study was performed to develop a management algorithm that accurately predicts the necessity of operative intervention and results in significant cost savings for patients with cystic pancreatic tumors. METHODS: We reviewed 60 patients treated between 1992 and 2003. Accuracy rates of tests used to differentiate benign from premalignant and malignant cysts were calculated. A management algorithm was generated that incorporated clinical presentation, radiologic findings, and selective use of endoscopic procedures. This algorithm was tested for predictive accuracy, and savings between actual management and proposed management were compared. RESULTS: There was an average of 3 preoperative tests performed per patient. Endoscopic procedures included endoscopic retrograde cholangiopancreatography in 21 patients and endoscopic ultrasound in 25 patients. A cyst fluid carcinoembryonic antigen (CEA) level of 158 ng/mL or greater had an accuracy rate of 87.5% that was significantly higher than endoscopic retrograde cholangiopancreatography (72%), endoscopic ultrasound morphology (45%), or endoscopic ultrasound cytology (66.7%). There was no combination of tests that provided greater accuracy than cyst fluid CEA level alone (P < .05). The management algorithm had a positive predictive value of 81%. The average actual cost of radiographic and endoscopic procedures was dollar 8,080 per patient. The proposed cost based on the algorithm was dollar 6,677 with a savings of dollar 1,403 per patient (P = .009). CONCLUSIONS: In patients with clinical symptoms or radiographic findings of mucinous or malignant tumors, further testing is excessive. Of endoscopic tests available, the cystic fluid CEA level most accurately predicts the presence of a mucinous neoplasm. A management algorithm based on presenting symptoms, radiographic findings, and cyst fluid CEA level provides a guideline for the evaluation of cystic lesions in the most cost-efficient manner while ensuring proper care.

Deletion of a malaria invasion gene reduces death and anemia, in model hosts.

Malaria parasites induce complex cellular and clinical phenotypes, including anemia, cerebral malaria and death in a wide range of mammalian hosts. Host genes and parasite 'toxins' have been implicated in malarial disease, but the contribution of parasite genes remains to be fully defined. Here we assess disease in BALB/c mice and Wistar rats infected by the rodent malaria parasite Plasmodium berghei with a gene knock out for merozoite surface protein (MSP) 7. MSP7 is not essential for infection but in P. falciparum, it enhances erythrocyte invasion by 20%. In vivo, as compared to wild type, the P. berghei Δmsp7 mutant is associated with an abrogation of death and a decrease from 3% to 2% in peak, circulating parasitemia. The Δmsp7 mutant is also associated with less anemia and modest increase in the size of follicles in the spleen. Together these data show that deletion of a single parasite invasion ligand modulates blood stage disease, as measured by death and anemia. This work is the first to assess the contribution of a gene present in all plasmodial species in severe disease.