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This study investigated the effect of bone regeneration with dental pulp stem cells (DPSCs), deciduous tooth stem cells (DTSCs), or bone-marrow-derived mesenchymal stem cells (BMMSCs) for clinical study on hydroxyapatite-coated osseointegrated dental implants, using tissue engineering technology. In vitro, human DPSCs and DTSCs expressed STRO-1, CD13, CD29, CD 44, CD73, and osteogenic marker genes such as alkaline phosphatase, Runx2, and osteocalcin. In vivo, prepared bone defect model was implanted using graft materials as follows: platelet-rich plasma (PRP), PRP and canine BMMSCs (cBMMSCs), PRP and canine DPSCs (cDPSCs), PRP and puppy DTSCs (pDTSCs), and control (defect only). After 8 weeks, the dental implants were installed, and 16 weeks later the sections were evaluated histologically and histometrically. The cBMMSCs/PRP, cDPSCs/PRP, and pDTSCs/PRP groups had well-formed mature bone and neovascularization. Histometrically, the bone-implant contact was significantly different between the cBMMSCs/PRP, cDPSCs/PRP, pDTSCs/PRP groups, and the control and PRP groups (p < 0.01). These results demonstrated that these stem cells with PRP have the ability to form bone, and this bone formation activity might be useful for osseointegrated hydroxyapatite-coated dental implants with good levels of bone-implant contact.

Introduction: Mesenchymal stem cells (MSCs) have been used for clinical application in tissue engineering and regenerative medicine (TERM). To date, the most common source of MSCs has been bone marrow. However, the bone marrow aspirate is an invasive and painful procedure for the donor. Thus, the identification and characterization of alternative sources of MSCs are of great importance. This study focused on the characterization of stem cells from human exfoliated deciduous teeth (SHED) compared with dental pulp stem cells (DPSCs) and bone marrow-derived mesenchymal stem cells (BMMSCs)., Methods: We have compared "stemness" such as the proliferation rate and the expression of stem cell marker of DPSCs, SHED, and BMMSCs. In addition, gene expression profile of DPSCs and SHED were analyzed by using DNA microarray., Results: All cells isolated from the three sources exhibited MSC characteristics including a fibroblastic morphology, and the expression of mesenchymal stem-cell markers. The proliferation rate of SHED was significantly higher than that of DPSCs and BMMSCs (P < 0.05). The comparison of the gene expression profiles indicated 4386 genes with a changed expression between DPSCs and SHED by 2.0-fold or more. Higher expression in SHED was observed for genes that participate in pathways related to cell proliferation and extracellular matrix, including several cytokines such as fibroblast growth factor and tumor growth factor beta., Conclusions: Because of its advantages of a higher proliferation capability, abundant cell supply, and painless stem cell collection with minimal invasion, SHED could be a desirable option as a cell source for potential therapeutic applications.

Purpose: The study aims to evaluate if human keratinocyte growth factor (hKGF), secreted after transduction of murine salivary glands with adenoviral vectors, can prevent oral mucositis resulting from radiation., Experimental Design: Two serotype 5 adenoviral vectors encoding hKGF were constructed: AdEF1alpha-hKGF and AdLTR(2)EF1alpha-hKGF. Female C3H mice, 8 weeks old, were irradiated by single (22.5 Gy) or fractionated (5 x 8 Gy for 5 days) doses to induce oral mucositis (ulcers on tongue). One day before irradiation, the above viral vectors or an empty vector, Adcontrol, was given (10(10) particles per gland) to both submandibular glands by retrograde ductal instillation. Each experiment included five groups: no irradiation and irradiation (+/-Adcontrol, AdEF1alpha-hKGF, or AdLTR(2)EF1alpha-hKGF). Blood, saliva, submandibular glands, and tongue were collected on day 7 for single-dose studies or day 10 for fractionated dosing. hKGF levels were measured by ELISA., Results: In three separate single-dose irradiation experiments, lingual ulcers were dramatically reduced after either KGF-expressing vector. Similarly, in two separate fractionated irradiation experiments, the hKGF-expressing vectors completely prevented ulcer formation. QPCR data indicated that approximately 10(7) to 10(8) particles of each vector remained in the targeted submandibular glands at the terminal time. Transgenic hKGF protein was found at high levels in saliva, serum, and submandibular gland extracts., Conclusions: hKGF gene transfer to salivary glands prevented radiation-induced oral mucositis in mice. This proof of concept study suggests that transgenic hKGF secreted from transduced salivary glands may be useful clinically to prevent oral mucositis caused by radiation.

There is no satisfactory conventional treatment for patients who experience irreversible salivary gland damage after therapeutic radiation for head and neck cancer or because of Sjögren's syndrome. Additionally, if most parenchyma is lost, these patients also are not candidates for evolving gene transfer strategies. To help such patients, several years ago we began to develop an artificial salivary gland. In the present study, we used a non-human primate tissue source, parotid glands from rhesus monkeys, to obtain potential autologous graft cells for development of a prototype device for in situ testing. Herein, we present 3 major findings. First, we show that primary cultures of rhesus parotid gland (RPG) cells are capable of attaining a polarized orientation, with Na(+)/K(+)-adenosine triphosphatase, zonula occludens-1, and claudin-1 distributed in specific domains appropriate for epithelial cells. Second, we show that RPG cells exhibit 2 essential epithelial functions required for graft cells in an artificial salivary gland device (i.e., an effective barrier to paracellular water flow and the generation of a moderate transepithelial electrical resistance). Third, we show that RPG cells can express functional water channels, capable of mediating directional fluid movement, after transduction by adenoviral and adeno-associated virus type 2 vectors. Together these results demonstrate that it is feasible to individually prepare RPG cells for eventual use in a prototype artificial salivary gland.

Salivary glands have proven to be unusual but valuable target sites for multiple clinical gene transfer applications. Access to salivary glands for gene transfer is easy. Multiple studies in animal models have yielded proofs of concept for novel treatments for damaged salivary glands following therapeutic irraditation, in Sjögren's syndrome, and for gene therapeutics systemically by way of the blood-stream and locally in the oral cavity and upper gastrointestinal tract.

Various fluorinated diphenylmethanols were enantioresolved by the methods of chiral camphorsultam-dichlorophthalic acid (CSDP acid) and/or 2-methoxy-2-(1-naphthyl)propionic acid (MalphaNP acid) yielding enantiopure alcohols. Their absolute configurations were unambiguously determined by X-ray crystallography of CSDP esters and/or by the (1)H NMR anisotropy method of MalphaNP esters for the first time., (Copyright 2003 Wiley-Liss, Inc.)

meta-Substituted diphenylmethanols were enantioresolved by the method of chiral phthalic acid yielding enantiopure alcohols. Their absolute configurations were unambiguously determined by X-ray crystallography of chiral phthalate esters and/or by the (1)H NMR anisotropy method using 2-methoxy-2-(1-naphthyl)propionic acid., (Copyright 2003 Wiley-Liss, Inc.)

Background/aims: Patients with a choledochal cyst previously treated by internal drainage should undergo secondary cyst excision. The results of such secondary excisions have not yet been reported., Methodology: Over a 27-year period, 121 patients underwent excision of a choledochal cyst at our hospitals. Of these, 14 patients underwent secondary cyst excision following internal drainage. These patients were compared retrospectively with the remaining 107 patients who underwent primary cyst excision., Results: Blood loss and operative time were greater, and early and late post-operative complications were significantly more frequent in the secondary excision group. Wound infection (early complication), pancreatic stones (late complication), and hepatolithiasis (late complication) were significantly more common in the secondary excision group. Histologically, inflammation and biliary glands were more frequently seen in the resected bile ducts in the secondary excision group., Conclusions: The long-term results of secondary excision of choledochal cysts are worse than after primary excision. The frequent late complications may be related to the development of biliary glands as a consequence of cyst-enterostomy.

Background: Cyst excision is the treatment for patients with choledochal cysts. In general, many authors recommend intramural dissection between the outer and inner layers of the cyst or partial excision leaving part of the cyst in the pancreas to avoid pancreatic injury. However, because there are few large series with long-term follow-up periods, it remains unclear how much of the intrapancreatic portion of the cyst should be resected and what resection technique should be used., Study Design: During an 18-year period, 104 patients underwent excision of choledochal cysts at our hospitals. Twelve patients had partial excision of the cyst above the pancreas, and 17 had intramural dissection of the intrapancreatic portion. Seventy-five patients underwent complete excision of the intrapancreatic portion of the cyst by our new technique, in which the outer plane of the epicholedochal plexus is dissected, exposing the narrow distal segment connecting the cyst to the pancreatic duct. Our new technique was compared retrospectively with the other two techniques., Results: With our technique, the intrapancreatic cyst could be excised completely in 75 patients without any complications. Blood loss was significantly decreased when our technique was used compared to intramural excision. A pancreatic fistula occurred after intramural excision in one patient, and pancreatic stones formed several years after partial excision and intramural excision in three patients who proved to have residual cystic material in the pancreas., Conclusions: Our operative technique is safe and effective for the complete excision of the intrapancreatic portion of a choledochal cyst.

A five-year-old boy with a large saccular aneurysm of the thoracic descending aorta extending rightward in the mediastinum underwent operation. Through a left thoracotomy descending aorta was clamped during partial femoro-femoral bypass and a examination of somatosensory evoked potential of the spinal cord. Placing a vertical incision on the aorta, a orifice of the aneurysm was closed with a xenograft pericardial patch. The aneurysm was left untouched. Nine months after operation the aneurysm was not recognized on chest X-ray and computed tomography. Etiology was unknown.

Serum levels of nervous system-specific enolase (alpha gamma form plus gamma gamma form) were determined in 18 patients with neuroblastoma and in 40 control infants by means of a sandwich enzyme immunoassay method specific to the gamma subunit (or 14-3-2 protein) of enolase isozymes. Levels in patients with neuroblastoma were elevated (mean, 70.3; range, 6.2 to 330.0 ng/mL) when compared with those of control subjects (4.3 +/- 1.7 ng/mL). Most of the patients (6/7), whose serum nervous system-specific enolase level increased more than 100 ng/mL, died within 1 month. Serial measurements in patients with neuroblastoma receiving various therapies have revealed that there was a good correlation between serum nervous system-specific enolase levels and the course of the disease. These results indicate that the nervous system-specific enolase in serum may be a valuable marker for therapeutic monitoring of patients with neuroblastoma, as reported recently in patients with small-cell carcinoma of the lung.

Twelve patients with esophageal atresia with tracheoesophageal fistula (TEF) who were treated with delayed primary anastomosis were reviewed. All patients except two were classified as Waterston's group C, for whom multiple staged procedures usually can be considered. Gastrostomy for decompression was performed as the initial operation shortly after admission and adequate nutritional support was provided by a transpyloric or jejunostomy tube. Extrapleural division of the TEF and esophagoesophagostomy were delayed until these operations were considered safe to perform. Delayed primary anastomosis was done at varying ages from the 11th day of life to the 150th day. Eleven patients survived. It is concluded that the therapeutic program consisting of gastrostomy, enteral feeding and delayed division of TEF and esophagoesophagostomy is useful in treating poor-risk patients and should replace multiple staged procedures.