Faculty Bibliography

One hundred seventy-eight implants from three systems were placed in 89 type II diabetic patients at 13 Department of Veterans Affairs medical centers. Four failures (2.2 percent) were found at uncovering. The failure rate increased to 7.3 percent at the end of 1 year (nine additional failures). Study patients will be monitored for an additional 4 years. Initial results suggest that type II diabetic patients can be considered for dental implant therapy. © 1994 by Williams and Wilkins.

Healing of soft and hard tissues results from a progression of events initiated by injury and directed toward reestablishing normal structure and function. The ubiquity of proteoglycans in mammalian tissues virtually guarantees their involvement in tissue restitution. The dramatic advances in cellular and molecular biology in recent years have added significantly to understanding the specific roles played by proteoglycans in wound repair processes

The tumor suppressor genes p53, Rb, and DCC were studied in five human oral cancer cell lines (FaDu, SCC-4, HEp-2, 1483, and OEC-M1) and in primary normal human oral keratinocytes (NHOK). All tested cancer lines had similar amount of p53 messages to normal cells, but the cancer lines FaDu and SCC-4 contained significantly higher p53 protein levels than did the normal counterpart. Sequencing p53 cDNA for these cancer cells showed point mutations: In the FaDu cell line, a mutation of CGG to CTG occurred at codon 248; and in the SCC-4 cell line, a mutation of CCC to TCC occurred at codon 151. The HEp-2 and 1483 cancer lines translated very low levels of p53 protein compared to the normal counterpart. Sequencing of p53 cDNA for HEp-2 and 1483 lines showed no mutations. Southern and Northern analyses revealed that these cell lines harbored HPV-18 DNA and expressed the viral E6/E7 protein. The OEC-M1 line showed different restriction fragment length polymorphism for the p53 gene compared with other cells, and did not express p53. All oral cancer cell lines except the OEC-M1 cells expressed both phosphorylated and hypophosphorylated Rb proteins. Further, the OEC-M1 line expressed smaller sized hypophosphorylated Rb proteins compared with normal cells. Unlike the other cancer lines, the HEp-2 and OEC-M1 lines also did not contain DCC mRNAs. These data indicate that 'high risk' HPV infections and mutations of p53, Rb, and DCC genes are frequently found in oral cancer cells and may be associated with oral cancer

Fibrotic disorders of skin and other organs are typically associated with an abnormal accumulation of extracellular matrix. This study focuses on a matrix constituent, hyaluronan-which is known to be altered in fibrotic disorders of skin- and on CD44, a cell adhesion molecule and putative receptor for hyaluronan. Tissue samples were obtained from biopsies of human normal skin, normal cutaneous scar; and hypertrophic cutaneous scar. After culturing, cells were studied by single- and double-labeling immunohistochemistry using the two anti-CD44 monoclonal antibodies, BU-52 and J173, and a biotinylated hyaluronan binding complex probe, b-HABR. Certain cultures were pretreated with Streptomyces hyaluronidase to assess the dependency of CD44 expression on the presence of endogenous hyaluronan. CD44 expression, both in the presence and the absence of exogenous hyaluronan, was quantitated by radioimmunobinding assay. Overall glycosaminoglycan synthesis and identification of hyaluronan were accomplished by precursor incorporation assays and by quantitative cellulose acetate electrophoresis. CD44 was found to be a normal human adult fibroblastic antigen whose expression is markedly increased for hypertrophic scar fibroblasts compared with normal skin fibroblasts. Although hyaluronan was found to be the predominant glycosaminoglycan constituent of the pericellular matrix for these fibroblasts, CD44 attachment to the cell surface is neither mediated by hyaluronan nor is the presence of hyaluronan a prerequisite for CD44 expression. Exogenous hyaluronan induced a decline in measurable CD44 expression for normal skin fibroblasts but not for hypertrophic scar fibroblasts. These observations are compatible with current understanding of the way cells manage the hyaluronan economy of the extracellular matrix and emphasize phenotypic heterogeneities between fibroblasts derived from normal versus scar tissues

This study assessed the efficacy of high-molecular-weight sodium hyaluronate as a treatment for certain intracapsular temporomandibular joint (TMJ) disorders. One hundred twenty-one patients were studied at three test sites using a randomized, double-blind, placebo-controlled experimental design. Patients were selected on the basis of 1) confirmed diagnosis of either degenerative joint disease (DJD), reducing displaced disc (DDR), or nonreducing displaced disc (DDN); 2) nonresponsiveness to nonsurgical therapies; and 3) severe dysfunction as established by the Helkimo indices (HI), visual analog scales (VASs), and physical measurements of joint movement and joint noise (arthrophonometry [APM]). Subjects received a unilateral upper joint space injection of either 1) 1% sodium hyaluronate in physiologic saline (MedChem Products, Woburn, MA) or 2) USP physiologic saline. Clinical evaluations were performed using HI, VAS, and APM at weekly intervals for the first month and then at monthly intervals up to 6 months postinjection. Statistical analyses for both categorical and continuous variables were performed for each diagnostic category at each examination interval. For DJD, no difference in outcome was seen between treatment groups. For DDN, significant between-group differences were seen through 1 month; however, beyond this time point, the number of DDN patients was insufficient to draw meaningful conclusions concerning efficacy. For DDR, statistically significant within-group and between-group improvement in all three measures (HI, VAS, APM) was seen for the hyaluronate group compared to the saline group throughout the 6-month test period. At the month-2 and month-3 examination intervals, twice as many patients treated with hyaluronate (90%) showed improvement compared to patients given placebo. Further, only 3% of patients with DDR who were treated with hyaluronate relapsed compared with 31% of patients with DDR given placebo

Hyaluronate is a ubiquitous component of mammalian extracellular matrix. It influences numerous cellular processes and accumulates in fibrotic connective tissue disorders. Recently, hyaluronate catabolism has assumed additional importance because of the introduction into clinical practice of therapeutic procedures which deposit high concentrations of hyaluronate directly into tissues. Relatively little is known about the local metabolism, fate, or long-term effects of either endogenous or exogenous hyaluronate at deposition sites. A capacity for degrading hyaluronate within connective tissues, presumably by fibroblasts, has been inferred but remains controversial because direct proof that human fibroblasts endocytose and degrade hyaluronate has been lacking. In the present study, fibroblasts from normal and fibrotic skin were incubated with [3H]-hyaluronate. Binding and internalization of radiolabeled substrate were then measured: Binding assays revealed a saturable, dose-dependent increase in cell surface-associated [3H]-hyaluronate which was enhanced by pretreatment with hyaluronidase. Similar binding curves were obtained for all cells tested. All the cell lines internalized hyaluronate; however, fibroblasts in confluent cultures internalized 3.5- to 4.2-fold more radioactivity per cell than did fibroblasts from corresponding subconfluent cultures (p less than or equal to 0.002). Normal scar fibroblasts showed greater capacity for generating hyaluronate-derived partial degradation products. This work provides clear evidence that human cutaneous fibroblasts are capable of both binding and internalizing hyaluronate, possibly as a prerequisite for degradation

Chitosan, a complex carbohydrate derivative of shellfish exoskeleton, is shown to enhance lingual hemostasis in rabbits treated with a known antagonist of platelet function, epoprostenol (prostacyclin or PGI2). Bleeding times were measured for bilateral (15 mm x 2 mm) tongue incisions in 10 New Zealand white rabbits. Using a randomized, blinded experimental design, one incision in each animal was treated with chitosan and the other was treated with control vehicle without chitosan. Extraoral bleeding and coagulation times were measured for each animal before, during, and after infusion of epoprostenol. Continuous infusion of epoprostenol increased mean systemic bleeding time 95%. In this platelet dysfunction animal model, lingual incisions receiving the experimental substance showed a 56% improvement in bleeding time in comparison with lingual incisions receiving control solution (P = .003)