Role of indoleamine 2,3-dioxygenase in an inflammatory model of murine gingiva.

BACKGROUND AND OBJECTIVE: Indoleamine 2,3-dioxygenase (IDO) is one of the major pathways for metabolism of tryptophan in a variety of cells, including immune cells. Increasing evidence indicates that IDO is a critical player in establishing the balance between immunity and tolerance and ultimately in the maintenance of homeostasis. By inducing inflammation in gingival tissue, we tested the hypothesis that IDO is a pivotal player in regulating the immune and inflammatory responses of gingiva. MATERIAL AND METHODS: We utilized the IDO knockout mouse model in conjunction with lipopolysaccharide (LPS)-induced inflammation. Accordingly, wild-type and IDO knockout mice were injected with LPS or vehicle in the anterior mandibular gingiva, twice over a 2-wk period, which was followed by procurement of gingival tissue for histopathology and preparation of tissue for flow cytometry-based studies. RESULTS: Clinical and histological examinations revealed a marked adverse impact of IDO deficiency on gingival inflammation. These observations were consistent with a more marked increase in the number of cells positive for the proinflammatory cytokine interleukin (IL)-17, but no significant change in the number of cells positive for the anti-inflammatory cytokine IL-10, in LPS-treated IDO knockout mice. Consistent with the more marked proinflammatory impact of IDO deficiency, the percentage of regulatory T cells was much reduced in gingival tissue of LPS-treated IDO knockout mice than in gingival tissue of wild-type mice. These proinflammatory changes were accompanied with a prominent increase in apoptotic and necrotic cell death in gingival tissue of IDO knockout mice compared with wild-type mice. CONCLUSION: Collectively, our findings support a major role for IDO in the development of gingival inflammation, as an example of an inflammatory condition, and lay the foundation for subsequent studies to explore it as a novel immunotherapy target.

Accelerated NaCl-induced hypertension in taurine-deficient rat: role of renal function.

Taurine modulates blood pressure and renal function. As the kidney plays a pivotal role in long-term control of arterial pressure, we tested the hypothesis that taurine-deficient rats display maladaptive renal and blood pressure responses to uninephrectomy. Control and taurine-deficient (i.e., beta-alanine-treated) rats with either one or two remaining kidneys were fed diets containing basal or high (8%) NaCl diet. Urine osmolality was greater in the taurine-deficient than controls fed a normal NaCl diet; proteinuria and blood pressure were unaffected by uninephrectomy. Following 6 weeks on an 8% NaCl diet, the uninephrectomized (UNX) animals developed significant hypertension, which was more severe in the taurine-deficient group; baroreflex function was unaffected. However, the UNX taurine-deficient rats displayed impaired ability to dispose of an acute isotonic saline volume load before a switchover to a high NaCl diet. Nonetheless, a more protracted exposure (i.e., 14 weeks) to dietary NaCl excess eliminated the blood pressure differential between the two groups; at this stage, renal excretory responses to an acute saline volume load or to atrial natriuretic peptide were similar in the two groups. Nonetheless, hypertensive taurine-deficient rats displayed greater proteinuria, although both groups excreted proteins of similar molecular weights ( approximately 15-66 kDa). Further, taurine-deficient kidney specimens displayed periarterial mononuclear cell infiltrates with strong immunoreactivity to the histiocyte marker CD68, suggestive of increased phagocytic activity. In conclusion, taurine deficiency modulates renal adaptation to combined uninephrectomy and dietary NaCl excess, resulting in an accelerated development of hypertension.

Gigantiform cementoma: clinicopathologic presentation of 3 cases.

Gigantiform cementoma is a rare, benign fibro-cemento-osseous disease of the jaws, seen most frequently in young girls. Radiographically, it typically presents as multiquadrant, expansile, mixed radiolucent-opaque lesions that cross the midlines of the jaws. Although cases with a familial pattern are noted in a few publications, sporadic cases have been reported without a family history. The term gigantiform cementoma has been used interchangeably with designations of other fibro-osseous entities, yet its application should be restricted by the criteria defined herein. In this article, we report 3 cases of gigantiform cementoma. Clinical, radiographic, and microscopic features of these lesions are presented, along with criteria to differentiate gigantiform cementoma from other fibro-osseous diseases of the jaws. A possible pathogenetic mechanism and treatment recommendations are discussed.

Immunohistochemical evaluation of basal cell carcinoma and trichepithelioma using Bcl-2, Ki67, PCNA and P53.

Most basal cell neoplasms with follicular differentiation represent a heterogenous group of tumors. Although may arise anywhere in the skin, these neoplasms commonly occur on the head and neck regions. The majority of these neoplasms are basal cell carcinomas (BCC) and trichoepitheliomas (TE). Overlapping histopathologic features between these benign and malignant tumors are occasionally seen which may create problems in rendering a definitive diagnosis. The intent of this investigation was two-fold: 1) to examine whether there are quantitative differences of the cellular expression of Bcl-2, Ki67, PCNA and P53 between BCC and TE; and 2) to examine the value of these immunostains in differentiating between BCC and TE. Twenty cases of BCC were stained with antibodies for Bcl-2, Ki67, PCNA and P53. The positive cell indices and staining characteristic of these immunostains were compared with those of 20 cases of TE. The cell indices for each group were analyzed statistically utilizing the analysis of variance (ANOVA) technique. Intensity and patterns of Bcl-2 and P53 expression were similar between BCC and TE. The ANOVA analysis showed no statistically significant differences between cell indices for cases stained with antibodies for Bcl-2 and P53 (p=0.49 and p=0.87 respectively) in the two neoplastic groups. There were intense labelling and generalized patterns of Ki67 and PCNA expression in BCC. Conversly, Ki67- and PCNA-labelled cells were much fewer in TEs than those noted in BCCs. Additionally, Ki67- and PCNA-positive cells were limited to the peripheral layers of the neoplastic islands of TEs. There were statistically significant differences between cell indices for cases stained with antibodies for Ki67 and PCNA (p=0.02 and p=0.05 respectively) in the two neoplastic groups. BCC and TE exhibited comparable expressions of Bcl-2 and P53 with similar intensity of labelling and patterns of distribution. This suggests possible similar mechanisms of growth regulation in both neoplasms. However, Ki67 and PCNA labelling was noted with significantly increased numbers and recognizably different patterns in BCCs compared to TEs. This may help explain the significant capabilities in tumor proliferation and the aggressive behavior of BCC compared to the limited growth potential of TE. Additionally, Ki67 and PCNA staining intensity and characteristics may have some value in differentiating between BCC and TE.

A case report of subpontic osseous hyperplasia in the maxillary arch.

Subpontic osseous hyperplasia has been portrayed in both the historical and the current literature as occurring exclusively in the mandibular posterior region. This article presents the clinical, radiologic, and microscopic documentation of subpontic osseous hyperplasia occurring in the maxillary first molar region.

Eosinophilic granuloma: a case report with pathologic fracture.

Approximately 10% to 20% of all cases of eosinophilic granuloma occur in the jaws. A palpable mass with or without pain is the most frequent presenting clinical feature. Less common clinical signs include gingivitis, loose teeth, and oral ulceration with poor healing. We report a case of monostotic mandibular eosinophilic granuloma in a 38-year-old woman that initially manifested mandibular body fracture, an unusual and poorly documented clinical sign for this disease. The clinical and radiographic features, differential diagnosis, and treatment plan of the case are presented.

Glial choristoma of the tongue: a case report and review of the literature.

Heterotopic brain tissue is an extremely rare developmental malformation. It is considered to be one of the very rare choristomatous lesions involving the oral cavity. We present a case of glial choristoma located on the dorsal surface of the tongue, midline area, in an 8-month-old African-American female baby. The clinical, histologic, and immunohistochemical features are presented. In addition, a review of previously reported cases and their probable embryogenesis are analyzed.

Adenosquamous carcinoma: a case report with immunohistochemical evaluation.

The histogenetic origin of adenosquamous carcinoma, a high-grade variant of malignant epithelial neoplasm, has long been debated. We report a case that clearly demonstrated a mucosal surface epithelial origin. This concept was supported through histologic analysis of hematoxylin- and eosin-stained sections, as well as by the pattern of immunohistochemical reactivity with antibodies directed against low and high molecular weight cytokeratins, cell adhesion molecules (CAM 5.2), and carcinoembryonic antigens. The histologic differential diagnosis, biological behavior, and prognosis of adenosquamous carcinoma are also examined.

Study of human papillomavirus in oral epithelial dysplasia and epidermoid carcinoma in the absence of tobacco and alcohol use.

Human papillomaviruses (HPVs) are implicated in the etiology of benign and malignant mucosal lesions in both human beings and animals. The oncogenic role of HPV in malignant cervical lesions is well supported by DNA hybridization techniques and epidemiologic studies. However, the role of HPV in oral epithelial dysplasia and epidermoid carcinoma remains speculative. In this study the in situ hybridization technique was used to detect HPV genotypes 6 and 11; 16 and 18; and 31, 33, and 35 in tissue specimens from a study group consisting of 18 patients who were non-tobacco users, or non-tobacco and non-alcohol users, in whom oral epithelial dysplasia and epidermoid carcinoma developed. The hybridization findings were compared with those of a comparable control group of patients with similar lesions who had a history of tobacco and alcohol use. None of the study group cases was reactive with any of the DNA probes. Two cases of the control group showed positive hybridization with HPV DNA probe types 6/11 and 16/18. The implications of these findings are presented and discussed in an attempt to clarify the role of HPV in HPV-associated oral epidermoid carcinomas.