Correlation between AIDS-related Kaposi sarcoma histological grade and in vitro behavior: reduced exogenous growth factor requirements for isolates from high grade lesions.

Kaposi sarcoma, the most common AIDS-associated malignancy, affects 10-30% of all AIDS patients. To date, research into the biological characteristics of AIDS-related Kaposi sarcoma (AIDS-KS) derived cell lines has been based on cultures established from skin explants or pleural effusions/peritoneal fluids. We have established several AIDS-KS lines from biopsy confirmed oral mucosal and epidermal AIDS-KS lesions and have found a correlation between AIDS-KS lesional grade and in vitro cellular growth characteristics. In comparison to epidermal AIDS-KS lesions, mucosal AIDS-KS lesions frequently possessed both a more advanced histologic grade and demonstrated a greater capacity to proliferate in minimal medium. We report the ability of AIDS-KS isolates from high grade lesions to sustain proliferation (greater than 60 population doubling levels) in medium not supplemented with endothelial cell growth supplement and/or cytokine rich conditioned medium. These findings indicate that AIDS-KS cells isolated from high grade lesions have reduced requirements for exogenously provided growth supplements, and suggest that increased autologous cytokine production accompanies AIDS-KS lesional progression.

Comparison of constitutive cytokine release in high and low histologic grade AIDS-related Kaposi's sarcoma cell strains and in sera from HIV+/KS+ and HIV+/KS- patients.

Kaposi's sarcoma (KS) is both an AIDS-defining disease and the most common HIV-associated malignancy. A cytokine-mediated pathogenesis for AIDS-KS is implicated because AIDS-KS-derived cell strains both respond to and express a variety of cytokines. We have reported the establishment of several (n = 18) AIDS-KS cell strains and determined that reduced exogenous growth factors are necessary to sustain proliferation in isolates from high histologic grade KS lesions. This current investigation explored the possibility that there are histologic grade-associated differences in either the qualitative and/or quantitative constitutive release of AIDS-KS growth stimulatory cytokines. Our findings showed that the incorporation of HTLV-II cytokine-rich conditioned media induced both qualitative and significant quantitative cytokine release, suggesting that exogenous growth promoters stimulate constitutive cytokine release. ELISA of our AIDS-KS cell strains demonstrated constitutive release of IL-6 (seven of seven), FGF-2 (five of seven), GM-CSF (three of seven), and IL-1 beta (one of seven). None of our AIDS-KS cell strains constitutively released detectable levels of Onco-M, IL-4, PDGF, TNF-alpha, or TNF-beta. In addition, we report that the method of cytokine result quantitation significantly affects reported cytokine levels. We determined that there was no significant histologic grade-dependent difference in the constitutive release of soluble cytokines by in vitro grown cultures of AIDS-KS cells. The presence of HIV influenced the sera cytokine profiles by elevating IL-6 and decreasing PDGF concentrations of HIV+ individuals relative to HIV- healthy controls. However, the presence of KS was not associated with unique serum cytokine profiles, because no differences were noted in comparisons of HIV+/KS+ versus HIV+/KS- individuals. Our findings suggest that the local environment is key in modulating AIDS-KS cytokine expression and that KS growth-promoting factors function at the local or paracrine, not the systemic, level. In conclusion, our previous results demonstrated a histologic grade-associated difference in the in vitro growth capacity of AIDS-KS cells; with high histologic grade isolates displaying a marked growth advantage during culture in minimally supplemented media. Findings from this current study reveal that although the potential for a constitutive growth loop exists in the high-grade isolates, it is not reflected in the free levels of soluble cytokines secreted into the culture medium.

Cultured AIDS-related Kaposi's sarcoma cells retain a proliferative bioenergetic profile but demonstrate reduced cytoprotective capabilities.

Features of AIDS-related Kaposi's sarcoma (AIDS-KS), such as the multifocal presentation at mucosal and epidermal sites subjected to trauma, suggest that AIDS-KS is initially a reactive hyperplasia that subsequently progresses to a neoplasia. It is recognized that there is an association between sustained inflammatory states and the subsequent development of neoplasia (e.g., ulcerative colitis/colonic adenocarcinoma). Furthermore, patients who develop AIDS-KS experience both a constant immune stimulation due to sustained high levels of virus-induced cytokines and, because of a sparing effect on their phagocytic cells, retention of the phagocytic inflammatory response. A component of phagocytic activation is the initiation of the oxidative burst, resulting in the generation of reactive oxygen species (ROS), which can be mutagenic to host cells if released beyond the phagolysosome and not inactivated. Our results demonstrate that cultured AIDS-KS cells possess decreased cytoprotective capabilities. Relative to either dermal fibroblasts, or human microvascular endothelial cells (HMECs), AIDS-KS cells contained significantly lower levels of glutathione, a tripeptide integral in both cytoprotection and maintenance of cellular thiol status. While HMECs increased catalase activity during culture in the cytokine-rich KS milieu (control medium supplemented with conditioned medium from MOT, an HTLV II-infected cell line), AIDS-KS cells demonstrated reduced catalase function under these conditions. Furthermore, HMEC cultures showed an inherent biochemical responsiveness, by increasing catalase activity following exposure to exogenous H2O2. In contrast, the catalase activity of AIDS-KS cells decreased following H2O2 challenge. Our results show that an inherent deficiency in cellular cytoprotection is present in AIDS-KS cells and suggest that oxidant stress may function in the development and progression of AIDS-KS.

Comparison of the resistance of miniplates and microplates to various in vitro forces.

A comparison of the Luhr Mini System (Howmedica, Inc, Rutherford, NJ) and the Luhr Micro System (Howmedica, Inc) was undertaken to determine resistance to various forces using a biomechanical model. Miniplates and microplates were first tested to determine their resistance to forces of displacement on flat bend, edge bend, tension, and compression generated by a materials testing system machine. Then, miniplates and microplates were attached to fresh porcine ribs, fixed to a custom-made jig, and subjected to the same forces of displacement. The load was applied to the bone plate to permanent deformation in all tests. The mini and microplate systems resisted 14.50 and 1.14 kg, respectively, on edgewise bending, 2.65 and 1.10 kg, respectively, on flat bending, 92.03 and 16.44 kg, respectively, on tension, and 127.9 and 27.02 kg, respectively, on compression. The mini and microsystem biomechanical model resisted 1.89 and 0.94 kg, respectively, on edgewise bending, 5.20 and 0.85 kg, respectively, on flat bending, 37.60 and 15.72 kg, respectively, on tension, and 53.55 and 16.0 kg, respectively, on compression. The results suggest that the Luhr Mini Fixation System provides a significant amount of resistance to tensile and compressive forces, but is weakest when large forces are applied at 90 degrees to the flat portion of the plate. The system showed decreased force resistance in the biomechanical model except on flat bending. The Luhr Micro Fixation System has significantly less resistance to deformation, but shows no decrease in ability to resist forces of displacement in the biomechanical model.

Self-stabilizing approach to surgical uprighting of the mandibular second molar.

A technique for surgical uprighting of malposed mandibular second molars is described. The principal advantage of this technique is that the tooth is stabilized by bone on the distal aspect of the uprighted tooth. Long-term clinical and radiographic follow-up reveals positional stability and no adverse pulpal or periodontal sequellae.

Evaluation and management of orofacial sensory nerve injuries.

Sensory disturbances can occur as a result of a number of dental procedures, maxillofacial injuries and pathology. The dentist is expected to inform patients of the likelihood of nerve injury prior to conducting invasive procedures. If a patient develops a sensory deficit after treatment, the practitioner should be aware of objective means of assessment of the deficit and techniques available for management. Our understanding of nerve injury, regeneration and treatment has markedly progressed in recent years. This paper provides current information on the prevention and management of neurosensory disturbances likely to be encountered in dental practice.

Lingual nerve injury as a complication of rigid fixation of the sagittal ramus osteotomy: report of a case.

This article describes a previously unreported complication of lingual nerve anesthesia and injury as a result of rigid fixation of the mandibular sagittal split osteotomy. The etiology of this injury is discussed and the surgical management using transoral microneurosurgical techniques is described.

Regenerative organization of the trigeminal ganglion following mental nerve section and repair in the adult rat.

Sequential double-fluorescence labeling techniques were employed to determine the regenerative somatotopic organization of first-order mandibular neurons following mental nerve transection and surgical repair in the adult rat. Twenty-four ganglia from 12 adult rats were examined microscopically in the following double-labeling paradigm: i) Fast Blue was injected directly into the mental nerves bilaterally; ii) 7 days later the nerves were transected and immediately rejoined by microscopic suture techniques; iii) Diamidino Yellow was then injected directly into the regenerated nerve, distal to the point of repair, 30, 60, and 90 days postrepair; and iv) the animals were sacrificed 3 days later and the ganglia removed for fluorescent microscopic examination. Results were compared with 12 ganglia each of unrepaired/resected controls and sham surgery controls made in parallel. The organization of fluorescence-labeled mandibular cells followed an orderly somatotopic distribution along the lateral dorsoventral axis of the trigeminal ganglion in all groups. The difference in mean total number of fluorescence-labeled cells within and between groups was insignificant or minimal. There was no evidence of heteronymous (nonmandibular) or homonymous (mandibular) sprouting following neuronal regeneration. Regeneration, as determined by the presence of double-labeled cells, was negligible if the transection injury was not repaired but significant 30 days following repair. Additionally, mandibular regeneration gradually improved, as shown by the significant increase of double-labeling at 60 and 90 days postrepair. However, 90 days later, the percentage of regenerated cells had not reached sham control conditions. The results of these studies suggest that following nerve transection and immediate repair in the adult rat: i) mental sensory neuronal perikarya regenerate from and maintain an organized somatotopic area within the mandibular division of the trigeminal ganglion; ii) reorganization by collateral sprouts from nonmental sensory mandibular and/or nonmandibular trigeminal ganglion cells is not evident or is negligible in the adult rat; and iii) regeneration of resected trigeminal sensory neurons is a gradual process which is enhanced by immediate surgical intervention.

Skin graft vestibuloplasty exostosis. A report of two cases.

Two cases of exostosis developing after mandibular vestibuloplasty and floor-to-mouth lowering with split thickness skin graft are presented, one with multiple recurrences. The lesion is clinically and microscopically described. Hypotheses with respect to the development of this phenomenon are proposed.