Periapical central giant cell granuloma: a potential endodontic misdiagnosis.

This retrospective study ascertained the incidence and clinicopathologic features of central giant cell granulomas (CGCGs) associated with teeth with necrotic pulps or teeth that had received previous endodontic treatment and determined whether periapical CGCGs can result in endodontic misdiagnosis. Clinical and histopathologic data of biopsy specimens diagnosed as CGCG were collected from the archives of the Oral Pathology Laboratory, Temple University, and were reviewed. Over the 9-year period, 16 of 79 cases (20%) of CGCG were associated with a tooth that had a history of pulp necrosis. Of those, 14 (88%) were associated with previous root canal treatment. The data from this series of 79 cases of CGCG also showed that CGCGs were less common in women, less common before age 30, and did not cross the midline of the jaw as often as previously reported. Clinical and histopathologic data were compared from (1) CGCGs associated with teeth with vital pulps or that occurred in edentulous areas; (2) CGCGs associated with teeth with necrotic pulps; and (3) 194 cases of periapical granulomas and radicular cysts. These data strongly suggest that CGCGs associated with teeth with necrotic pulps are not directly related to periapical inflammation and may be misdiagnosed as endodontic lesions. Posttreatment follow-up and routine submission of periapical surgical specimens are emphasized.

Segmental odontomaxillary dysplasia: a case report and review of the literature.

Segmental odontomaxillary dysplasia (SOD) is a rare, unilateral developmental disorder of the maxilla involving abnormal growth and maturation of the bone, lack of one or both premolars, altered primary molar structure, delayed tooth eruption, and fibrous hyperplasia of the gingiva. In this, the twenty-third reported case of SOD, the literature is reviewed, and the clinical, radiographic, and histopathologic data are described. Computed tomographic scans of this case showed that the involved segment of the maxilla extends mesiodistally from the permanent cuspid to the mesial portion of the first permanent molar, largely limited to the area of the missing premolars. However, the affected bone extends superiorly in the lateral wall of the maxilla to the zygoma and base of the orbit. This article is intended to serve as baseline data for a future article, describing the natural history and possible treatment of SOD, which remain undocumented.

The odontogenic keratocyst: a potential endodontic misdiagnosis.

Odontogenic keratocysts manifest themselves as radiolucencies that can appear anywhere in the maxilla or mandible, including periradicular areas; they may thus masquerade as lesions of endodontic origin. This retrospective study examined 239 odontogenic keratocysts received by the Oral Pathology Laboratory at Temple University School of Medicine over a 3-year period. Twenty-one (9%) of the cysts received were located periradicularly; of these 21, 12 (57%) were associated with nonvital or endodontically treated teeth and thus mimicked lesions of endodontic origin. Because of its aggressive nature and tendency to recur, the periradicular odontogenic keratocyst should be included in the differential diagnosis of lesions that are refractory to endodontic treatment.

Gastric cytoprotection is secondary to increased mucosal fluid secretion: a study of six cytoprotective agents in the rat.

We tested the hypothesis that rapidly developing gastric cytoprotection produced by topical application of exogenous compounds is a result of increased gastric mucosal fluid secretion. Ex vivo gastric chambers were prepared in rats which were subsequently exposed topically to one of the prostaglandin (PG) E1 analogues misoprostol or rioprostil, PGE2, nicotine, N-ethylmaleimide (NEM), 0.25 M HCl, or to their respective vehicles. All agents were added to empty chambers to avoid complications resulting from dilution by gastric contents. Effects of these agents on intraluminal volume changes, blood flow, juxtamucosal pH, histology, and on the mucosal damage resulting from necrotizing agents were studied. All six agents were cytoprotective and each increased net secretion of fluid by the chambered mucosae. Gastric blood flow was not significantly increased by NEM, by 0.25 M HCl, or by nicotine compared to controls, and the juxtamucosal pH was not significantly increased by any of the three agents for which this was studied. Vacuole formation in surface epithelial cells and subepithelial edema were seen after exposure to some agents, but none of the agents led to formation of a thick barrier of exfoliated cells and mucus. Ablation of primary afferent nerves with capsaicin abolished both protection by 0.25 M HCl and the net increase in fluid secretion by the mucosae. Capsaicin ablation did not alter either the protection afforded by NEM or the increase in volume of secretion. We conclude that increased mucosal fluid secretion is the common factor present with all six cytoprotective agents and hence may be the predominant mechanism of cytoprotection against topically applied necrotizing agents.

The hybrid xenograft/autograft bioprosthetic heart valve: in vivo evaluation of tissue extraction.

The major functional problem with bioprostheses is poor long-term durability. Bioprosthetic valves fail because of calcification and mechanical fatigue, both of which result from the glutaraldehyde fixation process. In an effort to develop a biologically active, non-cross-linked bioprosthetic valve, we devised a cellular extraction process. We tested the mechanical integrity of the processed valves and cultured both human and porcine cells on this material. To test the potential for calcification, we implanted strips of fresh, extracted, and glutaraldehyde-treated porcine heart valve tissue subcutaneously into 3-week-old Sprague Dawley rats for 21 days. We used atomic absorption spectroscopy to measure the extent of calcium accumulation and histopathologic assessment to evaluate the antigenic response. We found that the cell extraction process significantly reduced the propensity of the material to calcify in vivo (mean +/- standard deviation, 4.12 +/- 1.02 mg/g calcium extracted versus 10.75 +/- 3.9 mg/g calcium fresh versus 79.6 +/- 18.3 mg/g calcium glutaraldehyde fixed) but increased the antigenicity, as evidenced by increased cellular activity and resorption. Although they may reduce calcification, conventional detergent-based cell extraction techniques do not completely remove porcine aortic valve antigens and may in fact increase the antigenicity of the valve cusp material.

Localization of transforming growth factor beta and its natural inhibitor decorin in the human placenta and decidua throughout gestation.

Transforming growth factor beta (TGF beta) produced at the human fetomaternal interface has been shown to play a crucial role in controlling trophoblast invasion of the uterus. Decorin, a naturally occurring chondroitin-dermatan sulphate proteoglycan which binds TGF beta can inhibit its activity. In this study, immunohistochemical techniques were used to determine the locations of TGF beta and decorin within the human placenta and decidua throughout normal gestation. In addition, sites of TGF beta 1 mRNA synthesis were identified in early and late placenta by in situ hybridization. Results revealed the presence of immunoreactive TGF beta in the cytoplasm of villous syncytiotrophoblast and extravillous trophoblast cells throughout gestation. TGF beta immunostaining was absent from villous cytotrophoblast at all gestational ages examined. The extracellular matrix (ECM) of the villous core at all stages of gestation and cells of the cytotrophoblastic shell of the term placenta were immunoreactive for TGF beta. Within decidual tissue, TGF beta was primarily localized in the ECM during the first trimester and only a small proportion of decidual cells exhibited intracellular labelling. At later gestational ages the majority of decidual cells showed intracellular labelling accompanied by a decrease in ECM staining. This switch may reflect increased TGF beta synthesis by the decidual cells, decreased release, or altered TGF beta binding to one or more ECM proteins. In situ hybridization indicated that TGF beta 1 mRNA was primarily localized to the syncytiotrophoblast cell layer with low intensity signals present in extravillous trophoblast cells, in trophoblast cell columns, and in large decidual cells. At term, TGF beta 1 mRNA was located in both the syncytiotrophoblast and villous mesenchymal cells. Decorin was immunolocalized to the ECM of the mesenchymal core of the chorionic villi throughout gestation and no immunoreactivity was observed in either villous or extravillous trophoblast. In the first trimester decidua, decorin was localized to the ECM whereas decidual cells, decidual leucocytes, and the uterine epithelium were negative. At later gestational ages, the ECM as well as a few decidual cells displayed weak immunoreactivity. A strong co-localization of TGF beta and decorin in the ECM of first trimester decidual tissue suggests that decorin may aid TGF beta storage or limit its activity in the ECM.

Relative incidence of odontogenic tumors and oral and jaw cysts in a Canadian population.

The diagnoses of 40,000 consecutively accessioned oral biopsies from the Oral Pathology Diagnostic Service, University of Western Ontario, London, Canada, were reviewed. All odontogenic neoplasm, neoplasm-like lesions (tumors), and true cysts of the oral tissues and jaws were listed. Clinical data were reviewed, and microscopic diagnoses were confirmed for cases in which diagnoses were ambiguous. Records of all cases were examined to identify distant referrals that were not representative of the study population. Of a total of 445 (1.11%) odontogenic tumors, 392 (0.98%) were lesions from patients in the usual local drawing area of the biopsy service; 53 were referred from distant centers. From the local population, odontomas were by far the most common tumor (51.53%) followed by ameloblastomas (13.52%) and peripheral odontogenic fibromas (8.93%). Locally, radicular (periapical) cysts were the most common odontogenic cyst (65.15%) followed by the dentigerous cyst (24.08%) and the odontogenic keratocyst (4.88%). The most common nonodontogenic cyst was the nasopalatine duct cyst that accounted for 73.43% of this subset of cysts. Surprisingly few studies of this type are available, especially for odontogenic tumors. These data are important to assess geographic differences in the incidence of lesions and to allow clinicians to make realistic judgments in counseling patients before biopsy about the probability of diagnosis and risks associated with nonspecific clinical or radiographic lesions.

Mapping the locations of the epitopes of five monoclonal antibodies to the core protein of dermatan sulfate proteoglycan II (decorin).

Antibodies to dermatan sulfate proteoglycan II (decorin) have been used to study various aspects of the structure, function, and occurrence of this proteoglycan. The epitopes of five monoclonal antibodies (7B1, 5D1, 3B3, 6D6, and 1XA) were localized to specific cyanogen bromide fragments of the protein core separated by gel filtration. One large (159 residue) cyanogen bromide peptide was further digested with endoproteinase Lys-C and the peptides separated by reversed phase high performance liquid chromatography. In this way sequences of a suitable length (21-52 residues) for epitope mapping by synthesis of overlapping hexa- and octapeptides were identified. For each of the five monoclonal antibodies a short linear sequence with antigenic activity, from 4 to 8 amino acids long, depending on the particular antibody, was identified. The locations of the epitopes were correlated with various properties of the protein core predicted from the known amino acid sequence. It was observed that, at most, only one was localized in a region predicted to involve a beta-turn. Although four epitopes were in regions predicted to be moderately hydrophilic, accessible, and flexible, one was located in a hydrophobic sequence predicted to be highly inflexible and inaccessible. The implications of this observation in relation to the function of this proteoglycan are discussed.

Langerhans' cell histiocytosis in association with periapical granulomas and cysts.

This report describes a series of six cases of inflammatory periapical disease with small aggregates of Langerhans cells as a minor component. Immunohistochemical findings confirm that the cells are phenotypically related to Langerhans cells. Aggregates of these cells are not normally found in radicular cysts or periapical granulomas and have been interpreted to represent chronic localized Langerhans' cells histiocytosis. Whether these lesions, which arise within the context of chronic inflammatory periapical disease, represent incipient eosinophilic granulomas or are a more benign, minimally destructive form of Langerhans' cell histiocytosis is unknown. Clinical follow-up suggests that these lesions remain localized and that curettage is adequate treatment.

Digestive enzyme levels and histopathology of pancreas disease in farmed Atlantic salmon (Salmo salar).

1. The pancreatic digestive enzyme activities of trypsin and chymotrypsin were assessed in vitro and were found to correlate well with the histological changes characteristic of pancreas disease (PD) in farmed Atlantic salmon (Salmo salar). 2. Pancreatic enzyme activity was assessed in vivo using the chymotrypsin specific substrate N-benzoyl-L-tyrosyl-p-aminobenzoic acid. In all cases, significantly less p-aminobenzoic acid was excreted by fish later found to be suffering from PD. 3. It is concluded that the in vitro digestive enzyme assay was effective in diagnosing PD with the in vivo method, indicating further promise for assessing exocrine pancreatic function.

Heterogeneity of antibodies to metallothionein isomers and development of a simple enzyme-linked immunosorbent assay.

A competitive enzyme-linked immunosorbent assay (ELISA) for the measurement of metallothionein (MT) in tissues and body fluids has been developed. The ELISA employs the IgG fraction of a rabbit antiserum to rat liver Cd-MT-2 polymer, a biotinylated secondary antibody, and peroxidase conjugated avidin. With a 1:4000 dilution of the immunoglobulins, typical standard curves (logit-log regression) provide a linear range of 0.1-100 ng for MT-2 and 10-1000 ng for MT-1. Fifty percent inhibition is accomplished with 15 ng and 250 ng for MT-2 and MT-1, respectively. Rat liver MT-1 and MT-2 containing different metals (Ag, Cu, and Zn) inhibited the antibodies as effectively as CdMT. However, the antibodies exhibited greater affinity for both Apo-MT isoforms. Previously reported discrepancies between results obtained by metal binding assays (e.g., Ag-hem binding) and radioimmunoassay for MT levels in tissues have been largely resolved. By addition of 1% Tween 20 to samples, the ELISA routinely estimated the total MT in samples of rat, mouse, and human liver and kidney at 88% of the value obtained by the silver-hem binding assay. Specific antibodies to MT-2 were purified from our antiserum by affinity purification using CH-Sepharose 4B coupled with rat liver MT-1. Estimation of MT in samples using purified MT-2 antibodies provided slightly lower values (72%) for MT in tissues as compared to the Ag-hem method. The predominant form of MT in tissues of control animals was found to be MT-2.(ABSTRACT TRUNCATED AT 250 WORDS)

Palisaded encapsulated neuroma of oral mucosa.

The palisaded encapsulated neuroma is a solitary, small peripheral nerve lesion that occurs primarily on the facial skin of middle-aged adults. We report a series of 13 cases of palisaded encapsulated neuroma occurring on oral mucosa. The lesions presented as solitary, firm, sessile, partly or completely encapsulated, 2 to 3 mm nodules in adults with a mean age of 51 years (median 55 years). Nine of the neuromas occurred on the hard palate; the remainder were found on the soft palate, lower lip mucosa, upper lip mucosa, and maxillary anterior alveolar ridge. None of the cases was associated with neurofibromatosis or multiple endocrine neoplasia syndrome type III. Microscopically, the tumors were characterized by a moderately cellular, fascicular proliferation of spindle cells that showed some areas of nuclear palisading, suggestive of schwannoma. Immunohistochemical stains revealed that the lesions were composed largely of S-100 protein-positive Schwann cells and variable numbers of peripheral nerve axons, which were identified by their positive neurofilament staining. The fibrous capsule of the lesions showed positive staining for epithelial membrane antigen, indicative of perineurium.

Cocaine treatment in neonatal rats affects the adult behavioral response to amphetamine.

This study investigated whether exposure to cocaine during critical periods of brain development alters the motor stimulating effects of amphetamine given in adulthood. Female rats received 50 mg/kg/day cocaine HCl SC or vehicle during either postnatal days 1-10 or 11-20. At 60-65 days of age, activity counts were collected over a 15-min baseline period. Subjects then received one of 3 doses (0, 0.1, 0.25 mg/kg) of d-amphetamine sulfate SC followed by a 90-min period of activity monitoring. Adult activity in 1-10-day cocaine-treated rats was different from vehicle-treated rats in response to 0.1 mg/kg amphetamine only. Adult activity in 11-20-day cocaine-treated rats was different from vehicle-treated rats in response to 0.25 mg/kg only. The observed differences represented an increase and decrease in activity, respectively. These alterations in amphetamine response may be related to the observed alterations in D-1 receptor concentrations as well as the altered rates of brain glucose metabolism we have observed in adult rats neonatally exposed to cocaine.

Immunoelectron microscopic localization of the core protein of decorin near the d and e bands of tendon collagen fibrils by use of monoclonal antibodies.

Two monoclonal antibodies, 6D6 and 7B1, previously shown to recognize different epitopes on different regions of the protein core of decorin were used to localize the protein core in relation to the positively stained bands in the D period of bovine tendon collagen fibrils. Peroxidase-antiperoxidase staining revealed that the antigen is associated with the surface of all fibrils and suggested that the axial distance between antigens is D-periodic. Immunoferritin labeling with each antibody produced a distribution of ferritin particles that showed that both epitopes of the protein core are localized near the d and e bands in the D period. The data indicate that the decorin protein core binding site(s) on tendon collagen fibrils is/are located near these bands, axially, within the D period.

Proteoglycans of the articular disc of the bovine temporomandibular joint. II. Low molecular weight dermatan sulphate proteoglycan.

The low molecular weight proteoglycan fraction extracted from articular discs with 4 M guanidinium chloride was found to consist predominantly of an iduronate-rich dermatan sulphate proteoglycan, together with chondroitin sulphate-containing material. The dermatan sulphate proteoglycan was purified by ion-exchange and gel-filtration chromatography and its core protein isolated after digestion with chondroitinase ABC. The amino acid composition and pattern of cyanogen bromide peptides obtained from this core were closely similar to those of the protein core of bovine skin proteodermatan sulphate. Four monoclonal antibodies raised against bovine skin proteodermatan sulphate also reacted with the disc protein core and its cyanogen bromide peptides. Results of digestion with glycopeptidase F demonstrated the presence of three N-linked oligosaccharides. The combined size of these oligosaccharides appeared to be somewhat less than the size of those on skin proteodermatan sulphate. The glycosaminoglycan chain released by digestion with cathepsin C had a higher molecular weight than that from skin. These differences in glycosylated structures may be responsible for the different effects on collagen fibrillogenesis in vitro; whereas skin proteodermatan sulphate only reduced the rate of fibril growth, disc dermatan sulphate proteoglycan also increased the length of the lag-phase and the final opacity.

Mineral-binding proteoglycans of fetal porcine calvarial bone.

To provide a more definitive characterization of the hydroxylapatite-associated proteoglycans (HAPG) of bone, proteins were extracted from the mineralized matrix of fetal porcine calvaria with 0.5 M EDTA in the absence of guanidine HCl. The small proteoglycans obtained in the extract were fractionated by gel filtration on Sepharose CL-6B, purified by ion-exchange chromatography on Polyanion matrix (fast protein liquid chromatography), and then separated into three major populations of chondroitin sulfate proteoglycans by chromatography on hydroxylapatite, all in the presence of 7 M urea. Based on immunological and chemical properties, two classes of bone proteoglycan were resolved. In one class (HAPG1), the proteoglycan and specific CNBr-derived peptides cross-reacted with three monoclonal antibodies that recognize different epitopes of the protein core of bovine skin proteodermatan sulfate. The other class of proteoglycan included two species (HAPG2, HAPG3) which were not recognized by these antibodies. In addition, these proteoglycans did not stain with Coomassie Blue R-250 nor with silver stain nor did they bind to nitrocellulose membranes used in Western blots. However, the cationic dye Stains-all stained both HAPG2 and HAPG3; the protein cores of these proteoglycans were stained a characteristic turquoise blue, whereas the protein core of HAPG1 was stained pink. The average Mr values of the bone proteoglycans, from gradient sodium dodecyl sulfate-polyacrylamide gel electrophoresis were: HAPG1, 120,000, with a protein core (chondroitinase AC-digested) of 45,000; HAPG2 and HAPG3, 110,000, with protein cores of 37,000-38,000. On 15% polyacrylamide gel electrophoresis, the protein cores of HAPG2 and HAPG3 migrated with an Mr 30,000, while HAPG1 protein core was unchanged (Mr 45,000). Based on amino acid analysis, the protein chains of HAPG2 and HAPG3 appear to be identical, although minor differences in the relative amount of glucosamine were evident. In contrast, the composition of HAPG1 was quite different, with higher relative amounts of hydrophobic and aromatic residues and lower amounts of Asx and Glx. The presence of 360 residues/1,000 of Asx and Glx in HAPG2 and HAPG3 may in part explain the characteristic staining and immunotransfer properties of these proteoglycans. The unique amino-terminal sequence of HAPG2 (Asn-Pro-Val-Ala-Arg-Tyr-Gln), together with the immunological and chemical properties, would indicate that HAPG2 and HAPG3 are novel proteoglycans and, unlike HAPG1, could be unique to mineralized tissues.

Chemical and immunochemical characteristics of proteoglycans in bovine gingiva and dental pulp.

Proteoglycans were extracted with 4 M guanidinium chloride at 6 degrees C and purified by ion-exchange chromatography and precipitation with cetyl-pyridinium chloride. Chromatography on Sepharose CL-4B under dissociating conditions separated larger (PG1) and smaller (PG2) proteoglycans. Gingival PG2, by virtue of its amino-acid composition and the exclusive presence of L-iduronate-rich dermatan sulphate, was a proteodermatan sulphate (PDS) with a similar molecular weight to periodontal-ligament PDS. Reaction with four monoclonal antibodies to bovine skin PDS confirmed the relationship between these small proteoglycans and that of skin. Their glycoprotein cores, liberated by digestion with chondroitinase ABC, were similar in size (mol. wt = 55,000 by SDS-gel electrophoresis). Pulp PG2 had a small amount of PDS but the main component contained D-glucuronate-rich sulphated galactosaminoglycans. Similar galactosaminoglycans, which included chondroitin sulphate, characterized the larger proteoglycans of gingiva and pulp; significant amounts of L-iduronic acid-rich dermatan sulphate or heparan sulphate were not present.

Dermatan sulphate is located on serine-4 of bovine skin proteodermatan sulphate. Demonstration that most molecules possess only one glycosaminoglycan chain and comparison of amino acid sequences around glycosylation sites in different proteoglycans.

Digestions of bovine skin proteodermatan sulphate with cathepsin C proved that the dermatan sulphate was located on Ser-4 in most of the molecules. A Ser-Gly sequence is essential for xylosylation of the serine residue and sulphated galactosaminoglycan synthesis in different proteoglycans. Variations in adjoining sequences may be significant in relation to the glycosylation process in different tissues.