Faculty Bibliography

Steel factor, the protein product of the Steel locus in the mouse, is a multifunctional signal for the primordial germ cell population. We have shown previously that its expression accompanies the germ cells during migration to the gonads, forming a "travelling niche" that controls their survival, motility, and proliferation. Here we show that these functions are distributed between the alternatively spliced membrane-bound and soluble forms of Steel factor. The germ cells normally migrate as individuals from E7.5 to E11.5, when they aggregate together in the embryonic gonads. Movie analysis of Steel-dickie mutant embryos, which make only the soluble form, at E7.5, showed that the germ cells fail to migrate normally, and undergo "premature aggregation" in the base of the allantois. Survival and directionality of movement is not affected. Addition of excess soluble Steel factor to Steel-dickie embryos rescued germ cell motility, and addition of Steel factor to germ cells in vitro showed that a fourfold higher dose was required to increase motility, compared to survival. These data show that soluble Steel factor is sufficient for germ cell survival, and suggest that the membrane-bound form provides a higher local concentration of Steel factor that controls the balance between germ cell motility and aggregation. This hypothesis was tested by addition of excess soluble Steel factor to slice cultures of E11.5 embryos, when migration usually ceases, and the germ cells aggregate. This reversed the aggregation process, and caused increased motility of the germ cells. We conclude that the two forms of Steel factor control different aspects of germ cell behavior, and that membrane-bound Steel factor controls germ cell motility within a "motility niche" that moves through the embryo with the germ cells. Escape from this niche causes cessation of motility and death by apoptosis of the ectopic germ cells.

To evaluate the sealing capability of external hexagon implant systems and assess the marginal fit, two groups (n = 10 each) were employed: SIN (Sistema de Implantes Nacional, Brazil) and Osseotite, (Biomet 3i, USA). Sealing capability was determined by placing 0.7 muL of 1% acid-red solution in the implant wells before the torque of their respective abutments. Specimens were then placed into 2.5 mL vials filled with 1.3 mL of distilled water with the implant-abutment interface submerged. Three samples of 100 muL water were collected at previously determinate times. The absorbance was measured with a spectrophotometer, and the data were analyzed by Two-way ANOVA (P < .05) and Tukey's test. Marginal fit was determined using SEM. Leakage was observed for both groups at all times and was significantly higher at 144 hrs. SEM analysis depicted gaps in the implant-abutment interface of both groups. Gaps in the implant-abutment interface were observed along with leakage increased at the 144 hrs evaluation period.

Lymphedema is a complication of cancer treatment occurring in approximately 50% of patients who undergo lymph node resection. Despite its prevalence, the etiology of this disorder remains unknown. In this study, we determined the effect of soft tissue fibrosis on lymphatic function and the role of transforming growth factor (TGF)-beta1 in the regulation of this response. We determined TGF-beta expression patterns in matched biopsy specimens collected from lymphedematous and normal limbs of patients with secondary lymphedema. To determine the role of TGF-beta in regulating tissue fibrosis, we used a mouse model of lymphedema and inhibited TGF-beta function either systemically with a monoclonal antibody or locally by using a soluble, defective TGF-beta receptor. Lymphedematous tissue demonstrated a nearly threefold increase in the number of cells that stained for TGF-beta1. TGF-beta inhibition markedly decreased tissue fibrosis, increased lymphangiogenesis, and improved lymphatic function compared with controls. In addition, inhibition of TGF-beta not only decreased TGF-beta expression in lymphedematous tissues, but also diminished inflammation, migration of T-helper type 2 (Th2) cells, and expression of profibrotic Th2 cytokines. Similarly, systemic depletion of T-cells markedly decreased TGF-beta expression in tail tissues. Inhibition of TGF-beta function promoted lymphatic regeneration, decreased tissue fibrosis, decreased chronic inflammation and Th2 cell migration, and improved lymphatic function. The use of these strategies may represent a novel means of preventing lymphedema after lymph node resection.

This study aimed to determine the mechanisms responsible for long-term tissue damage following radiation injury. We irradiated p21-knockout (p21(-/-)) and wild-type (WT) mice and determined the long-term deleterious effects of this intervention on mesenchyme-derived tissues. In addition, we explored the mechanisms of radiation-induced mesenchymal stem cell (MSC) dysfunction in isolated bone marrow-derived cells. p21 expression was chronically elevated >200-fold in irradiated tissues. Loss of p21 function resulted in a >4-fold increase in the number of skin MSCs remaining after radiation. p21(-/-) mice had significantly less radiation damage, including 6-fold less scarring, 40% increased growth potential, and 4-fold more hypertrophic chondrocytes in the epiphyseal plate (P<0.01). Irradiated p21(-/-) MSCs had 4-fold increased potential for bone or fat differentiation, 4-fold greater proliferation rate, and nearly 7-fold lower senescence as compared to WT MSCs (P<0.01). Ectopic expression of p21 in knockout cells decreased proliferation and differentiation potential and recapitulated the WT phenotype. Loss of p21 function markedly decreases the deleterious effects of radiation injury in mesenchyme-derived tissues and preserves tissue-derived MSCs. In addition, p21 is a critical regulator of MSC proliferation, differentiation, and senescence both at baseline and in response to radiation.

BACKGROUND: Physical and bioceramic incorporation surface treatments at the nanometer scale showed higher means of bone-to-implant contact (BIC) and torque values compared with surface topography at the micrometer scale; however, the literature concerning the effect of nanometer scale parameters is sparse. PURPOSE: The aim of this study was to evaluate the influence of two different implant surfaces on the percentage bone-to-implant contact (BIC%) and bone osteocyte density in the human posterior maxilla after 2 months of unloaded healing. MATERIALS AND METHODS: The implants utilized presented dual acid-etched (DAE) surface and a bioceramic molecular impregnated treatment (Ossean(R), Intra-Lock International, Boca Raton, FL, USA) serving as control and test, respectively. Ten subjects (59 +/- 9 years of age) received two implants (one of each surface) during conventional implant surgery in the posterior maxilla. After the non-loaded period of 2 months, the implants and the surrounding tissue were removed by means of a trephine and were non-decalcified processed for ground sectioning and analysis of BIC%, bone density in threaded area (BA%), and osteocyte index (Oi). RESULTS: Two DAE implants were found to be clinically unstable at time of retrieval. Histometric evaluation showed significantly higher BIC% and Oi for the test compared to the control surface (p < .05), and that BA% was not significantly different between groups. Wilcoxon matched pairs test was used to compare the differences of histomorphometric variables between implant surfaces. The significance test was conducted at a 5% level of significance. CONCLUSION: The histological data suggest that the bioceramic molecular impregnated surface-treated implants positively modulated bone healing at early implantation times compared to the DAE surface.

Objective:This study aimed (1) to investigate the relationship between the presence of lymph node central necrosis, viewed on pre-operative computed tomography imaging, and the occurrence of histopathologically determined metastatic lymph node extracapsular spread and (2) to determine whether a larger scale study would be valuable.Materials and methods:Pre-operative computed tomography scans, surgical records and post-operative histopathological analysis results were reviewed for 19 consecutive neck dissections performed in 17 patients with head and neck squamous cell carcinoma.Results:A total of 20/26 (77 per cent) lymph nodes with central necrosis had extracapsular spread on histopathological analysis. Twenty of 21 (95 per cent) lymph nodes with extracapsular spread had central necrosis on pre-operative computed tomography. Thirty-four of 40 (85 per cent) lymph nodes without extracapsular spread had no evidence of central necrosis on computed tomography. Only three of 12 (25 per cent) patients with lymph node central necrosis identified on pre-operative computed tomography were found to have actual necrosis on final histopathological analysis.Conclusions:Lymph node central necrosis viewed on pre-operative computed tomography scans is a useful indicator of metastatic lymph node extracapsular spread, with a sensitivity of 95 per cent, a specificity of 85 per cent, a positive predictive value of 69 per cent and a negative predictive value of 98 per cent. Lymph node diameter is not a sensitive indicator of extracapsular spread

Bony defects in the craniomaxillofacial skeleton remain a major and challenging health concern. Surgeons have been trying for centuries to restore functionality and aesthetic appearance using autografts, allografts, and even xenografts without entirely satisfactory results. As a result, physicians, scientists, and engineers have been trying for the past few decades to develop new techniques to improve bone growth and bone healing. In this review, the authors summarize the advantages and limitations of current animal models; describe current materials used as scaffolds, cell-based, and protein-based therapies; and lastly highlight areas for future investigation. The purpose of this review is to highlight the major scaffold-, cell-, and protein-based preclinical tools that are currently being developed to repair cranial defects