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Odontogenic keratocyst (OKC) was first described by Hans Philipsen in 1956. The World Health Organization (WHO) has designated OKC as a Keratocystic Odontogenic Tumor (KCOT). KCOT is defined as ′a benign uni- or multicystic, intraosseous tumor of odontogenic origin, with a characteristic lining of parakeratinized stratified squamous epithelium, with a potential for aggressive, infiltrative behavior′. Radiographically, most OKCs are unilocular, presenting a well-defined peripheral rim and a central cavity having satellite cysts. It is characterized by a thin fibrous capsule and a lining of keratinized stratified squamous epithelium, which is typically corrugated, usually about 6 to 10 cells in thickness, and generally without rete pegs. The present case report describes an unusual case of KCOT with minimal clinical presentation indicative of a tumor highlighting the potential difficulties in determining the diagnosis.

beta 1 and beta 4 integrins are receptors on epithelial cells mediating cell-extracellular matrix adhesion. Furthermore, alpha 2 beta 1 and alpha 3 beta 1 contribute to cell-cell adhesion. Laminin-5 in epithelial basement membranes (BMs) is a ligand for alpha 6 beta 4 and alpha 3 beta 1. Expression of different integrins and laminin-5 was studied in oral epithelium to characterize regional variations in these adhesion molecules. Monoclonal antibodies directed against alpha 2-alpha 6 beta 1/alpha 6 beta 4 and laminin-5 were examined in cryopreserved biopsies of normal mucosa by immunohistochemistry. Laminin-5 was expressed as a line along the BMs. The junctional epithelium showed a unique phenotype: Laminin-5 was detected in the internal BM at the tooth surface and in the external BM, where excessive laminin-5 was seen in the stroma. alpha 6 beta 4 was expressed in all cells of the junctional epithelium. Integrins alpha 4 beta 1 and alpha 5 beta 1 were not detected in the epithelia, whereas alpha 2 beta 1 and alpha 3 beta 1 showed differential expression. Epithelia with well-developed rete pegs and connective tissue papillae showed polarized alpha 3 beta 1 expression along the BM in the rete pegs, in contrast to negative expression at the tips of the connective tissue papillae. A variation in the suprabasal distribution of alpha 2 beta 1 and alpha 3 beta 1 was observed between epithelia from different regions. alpha 2 beta 1 and alpha 3 beta 1 were detected in basal/parabasal cells in keratinized epithelia, whereas there was increased suprabasal expression in nonkeratinized mucosa. These results indicate inhomogeneity in the basal cell population of oral squamous epithelia and differential expression of integrins, which may reflect differences in the underlying stroma. Laminin-5 deposits in the stroma underneath the junctional epithelium may indicate subclinical gingival inflammation.

Epidermal hyper-proliferation is a key feature of psoriasis, and a role for IGF-I in this process has previously been proposed. Herein we investigated the expression of IGF binding proteins in the psoriatic lesion and compared it with normal skin. With in situ hybridization, we found that IGFBP-3 mRNA was expressed in the basal layer of the epidermis in nonnal skin. IGFBP-3 was also detected immunohis-tochemically, exclusively in the basal layer. In the psoriatic lesion, IGFBP-3 mRNA was similarly limited to the basal layer despite the characteristic expansion of the basaloid keratinocyte compartment and was detected only in the suprapapillary epidermis, where IGFBP-3 mRNA was more abundant than in normal or uninvolved epidermis, and IGFBP-3 protein could be readily detected with specific antibody. As with IGFBP-3 mRNA, which represents the likely site of IGFBP-3 synthesis, IGFBP-3 was strictly limited to the basal keratinocytes of the suprapapillary epidermis. By using an antibody to the cell cycle antigen Ki67, we also showed that the suprapapillary epidermis, where IGFBP-3 expression was maximal, contained few keratinocytes undergoing mitosis, whereas the tips of the rete pegs, where IGFBP-3 expression was conspicuously absent, contained many keratinocytes undergoing mitosis. We suggest that IGFBP-3 is a growth inhibitor in basal keratinocytes and that absence of IGFBP-3 in the tips of rete pegs may contribute to epidermal hyper-proliferation in the psoriatic lesion.

The daily oral administration of 3 ml of two oils (So-5407 and So-1129) containing essential fatty acids (EFAs) for 16 weeks resulted in a transient increase in cell proliferative activity in the skin of female Large White pigs. The So-5407 oil contained 7% gamma-linolenic acid (GLA) whereas So-1129 was an oil of similar composition, but with no GLA. Hyperplasia of the epidermis was observed after the administration of both oils, and this was characterized by an increase in the size of the rete pegs. The maximum effect occurred at 4 weeks after the start of oil administration, at which time the number of viable cell layers had increased by a factor of approximately 1.5, and mean epidermal thickness (excluding the stratum corneum) was approximately 40% greater than that of the epidermis prior to oil administration. There was a marked increase in the labelling index (LI) of the basal cell layer of the epidermis in pigs receiving So-5407. Maximum LIs were quantified at 4 weeks after the start of administration and were 18.8 +/- 1.3% and 13.1 +/- 1.7% for pigs receiving So-5407 and So-1129, respectively. After this time the LI declined progressively and had returned to values within normal limits (P > 0.1) by 8 weeks after the start of administration of both oils. A similar pattern of change in the LI was seen in the follicular epithelium, although the peak values at 4 weeks after the start of oil administration of 12.2 +/- 1.8% and 10.8 +/- 0.9 for the groups receiving So-5407 and So-1129, respectively, were lower than in the epidermis. Labelled cells were also counted in the papillary dermis and maximum values were again seen at 4 weeks after the start of oil administration. Of the two oils, So-1129 had the greatest effect, with the number of labelled cells in the papillary dermis being a factor of three to four-fold higher than in skin prior to oil administration, between 2 and 12 weeks after the start of administration.

The retrocuspid papilla (RCP) is a poorly recognized entity. In one part of our study, we found 10 cases of lesions clinically compatible with RCP in 1150 consecutively examined patients. In another part of the study, we found 15 cases of RCP in more than 2000 consecutive cases of oral mucosal hyperplasia submitted as surgical biopsies during 1989-92. The lesions were situated in the attached gingiva, lingual to the two mandibular canines, often bilaterally. They were covered by normal pink mucosa with a size and a height each of 2-3 mm. Histologically, the RCP was a broad-based, often downfolded hyperplasia, covered with a parakeratinized epithelium of normal thickness. The rete pegs were often elongated and blunt, frequently bent inward toward the center. The lamina propria was mostly composed of a loosely arranged, delicate, fibrous connective tissue. The lesions could be classified into two groups by the presence or absence of stellate and occasionally multinucleated fibroblasts. Immunohistochemical staining with an FXIIIa antibody disclosed a population of reactive spindle-shaped cells, mainly localized in the connective-tissue papillae. These cells may be of pathogenetic importance.

The distribution patterns of nerve fibers immunoreactive (IR) to calcitonin gene-related peptide (CGRP), substance P (SP), and neuropeptide Y (NPY) in the dental pulp, periodontal ligament (PDL), and gingiva were studied and compared with the complete innervation visualized by antibody to protein gene product (PGP) 9.5 in adult cats. The pulp showed considerably denser nerve supply for PGP 9.5, CGRP, and SP than the periodontal tissues. Most of the pulpal fibers were CGRP-IR, and approximately three to four times more IR fibers were labeled with CGRP than SP. Most fibers in the odontoblast area penetrating into the dentin tubules were CGRP-IR. NPY-IR nerves were mainly observed in connection with the larger blood vessels in pulp and PDL. In the PDL most nerves were localized in the apical third in connection with blood vessels, but CGRP-IR fibers extending close to root cementum were often observed. Immunoreactivity to PGP 9.5 and CGRP was frequently found in cell-like structures in connection with Malassez epithelium in the PDL and in some round epithelial-like cells located in the base of gingival rete pegs.

— A quantitative, semiautomatic analysis of hislologic features of the specific inflammatory changes occurring on the dorsum of human tongue was made for 37 tongues. Well-documented hislologic differences belween clinically normal appearing tongue (control), atrophic, geographic and fissured tongue were shown quantitatively. The epithelium of atrophic tongue was thinner compared to the controls. Reduction of the thickness was due to the shortened or totally missing rete pegs. Epithelium of geographic and fissured longue showed irregular rete pegs. In fissured tongue heavy inflammation seemed to shorten the rete pegs. In atrophic tongue the connective tissue was thicker compared to the controls. This could be due to mild, chronic inflammation causing loose connective tissue described in atrophic tongue. Muscle cells of geographic tongue appeared lo be as in the controls, whereas in atrophic and fissured tongue the uppermost muscle cells were small and separated compared to the controls.

We describe 4 cases of gingival hyperplasia induced by nifedipine, together with clinical and histological findings. Hyperplasia of the interdental papillae was observed in all cases. Histologic examination showed multilayered epithelial parakeratosis with variations in the width, proliferation, reticulation and elongation of the rete pegs. Substitution of another drug and improvement of oral hygiene led to reduction of the gingival overgrowth without gingivectomy. These treatments are essential for gingival hyperplasia induced by nifedipine.

The goal of this study was to evaluate the histologic criteria used to establish the diagnosis of human papillomavirus (HPV)-associated disease, especially in borderline lesions. In a completely blinded study, 21 patients had one biopsy each of the cervix and vulva. Each specimen was evaluated by RNA and DNA in situ hybridization, a histologic diagnosis was rendered, and then each was evaluated for 12 histologic criteria commonly associated with HPV. On the cervix only binucleation and dysplasia correlated well with in situ hybridization. Koilocytosis correlated very strongly with the histologic diagnosis. On the vulva, koilocytosis, papillomatosis, elongated rete pegs, binucleation, and hypergranulosis correlated well with in situ hybridization. When four other pathologists reviewed the slides, they agreed on the histologic diagnosis and the presence of koilocytosis, binucleation, and dysplasia on the cervix but on none of the other criteria. On the vulva the pathologists disagreed on the overall diagnosis and the presence of any of the criteria with the exception of papillomatosis. Nonclassic histologic criteria should not, by themselves, be used to make the diagnosis of condyloma. The use of such terminology as "suggestive of condyloma" in histologic diagnoses should be avoided in favor of more descriptive terminology to avoid possibly unnecessary treatment for lesions of questionable significance.

The three types of lesions—Bowen’s disease, Queyrat’s erythroplasia, and squamous cell carcinoma-in-situ—once recognised as distinct entities have been regrouped into a single category by the International Society for the Study of Vulvar Disease (1976). The terms Bowen’s disease and Queyrat’s erythroplasia have been abolished, and these two together with intra-epithelial carcinoma simplex have been put into a single category as carcinoma-in-situ. As there are only subtle histopatho-logical differences (Kaufman and Gardner 1965), many overlapping similarities among them and occasionally wide variations of appearances in the same lesion, the pathologists are not often unanimous in their diagnoses (Woodruff and Hildebrandt 1958) of these conditions. Most importantly, the biological behaviour of these lesions are similar and often necessitate a similar mode of management. The Society has defined carcinoma-in-situ as disorientation of epithelial architecture which extends throughout the full thickness of the epithelium, not including surface layers above the granular zone, and put dysplasia under vulval atypia which may exist with or without dystrophy (International Society for the Study of Vulvar Disease 1976). In a small percentage of lesions, the epithelium may not be involved in its full thickness, and there may be squamous “pearls” at the tips of rete pegs with loss of the normal basal cell layer. The present trend is to encompass all intra-epidermal atypias as intra-epithelial neoplasia (VIN) in accordance with the criteria used for defining cervical intra-epithelial neoplasia.

Background: The potential of calcium channel blockers (CCBs) to induce gingival enlargement (GE) as well as the influence of diabetes mellitus on periodontal tissues has been well documented. This case report documents a conservative clinical approach to the management of felodipine-influenced gingival enlargement and displays a clinical and histologic case of felodipine-influenced GE in an undiagnosed type 2 diabetic patient. Methods: At the initial examination, a medical consultation was requested and two incisional biopsies were taken for pathological evaluation. The patient was diagnosed with uncontrolled type 2 diabetes. Felodipine was withdrawn and the diabetes was controlled before dental treatment was initiated. The patient then underwent selective extractions and full-mouth scaling and root planing as well as oral hygiene instructions. No surgical therapy was indicated. Results: The histological results demonstrated the presence of elongated rete pegs; fibrous hyperplasia; a low-grade chronic inflammatory infiltrate, predominantly consisting of lymphocytes; and collagen bundle groups randomly distributed. These features were similar to those present in other drug-influenced GE. Clinical results have demonstrated almost complete resolution of GE after the withdrawal of felodipine and the control of diabetes. Further improvements were seen after scaling and root planing and oral hygiene instructions. No recurrences were noted 12 months after initial therapy. Conclusions: This report demonstrated that the control of systemic factors seemed to have the most influence on success for this particular case. Since the control of diabetes was managed at the same time as the felodipine withdrawal, it remains difficult to speculate how these two factors impacted both the severity of the GE and the therapeutic results. More importantly, the conservative treatment rendered demonstrated the stability of periodontal status during maintenance phase and the avoidance of surgical interventions. J Periodontol 2005;76:1217-1222.

Intro: Pathophysiology of hypertrophic scar formation remains unclear, potentially involving mechanical strain, burns, or infection. We sought to specifically examine the role of mechanical strain in hypertrophic scars. To do so, we developed and characterized a novel murine model which uses mechanical strain to produce hypertrophic scars in mice. Methods: Paired incisions were created on C57BL6 mice (n = 20). After closure, mechanical strain was applied across one wound using a novel device; the other wound was a control. Starting at day 3, mechanical strain was increased every other day over 4 wks. Wounds were harvested each week, and examined histologically using Sirius red, DAPI, BrdU for proliferation, and caspase 3 for apoptosis. Results: Strained wounds showed features of hypertrophic scars: raised borders, loss of rete pegs and adnexal structures in the epidermis overlying scars, blood vessels that were perpendicular and fibrillary collagen that was parallel to skin surface. Features persisted beyond 6 months. Wound collagen deposition in strained wounds increased 6-fold at 1 wk and over 12-fold at 2–4 wks, in parallel to an increase in number of stromal cells within scar (28-fold). This resulted in an increase in number of cells per unit area of collagen (over 42%). In all wounds, there was no significant difference in proliferation. There was a significant reduction in blood vessel (4-fold) and fibroblast (3-fold) apoptosis at 1–4 wks in strained wounds. Conc: Mechanical strain alone is sufficient to produce hypertrophic scars in this model that are indistinguishable from human scars. Notably, hypertrophic scars appear to result from a marked reduction in apoptosis, rather than from a significant proliferation and upregulation of cellular collagen deposition, validating previous in vitro studies.

Idiopathic guttate hypomelanosis is a common leukodermic dermatosis of obscure origin, consisting of small 2- to 5-mm achromic or hypopigmented macules, mainly affecting the exposed upper and lower extremities. In a group of 400 consecutive dermatologic patients, idiopathic guttate hypomelanosis was much more prevalent in women than in men. However, in both sexes this prevalence became more common with advancing age. In another group of fifteen patients with idiopathic guttate hypomelanosis and fifteen normal controls matched by age, sex, and skin type, the following was found: A cause-effect relationship between chronic actinic exposure and the development of idiopathic guttate hypomelanosis could not be established by statistical studies. A family aggregation survey disclosed a higher prevalence of idiopathic guttate hypomelanosis in the family of patients with idiopathic guttate hypomelanosis than in the control group. Epithelial atrophy, patchy absence of melanocytes and melanin, flattening of the rete pegs, and basket weave hyperkeratosis were the most prominent histologic findings of idiopathic guttate hypomelanosis. Minigrafts of normal skin implanted in idiopathic guttate hypomelanosis lesions did not modify the achromic defects, whereas intralesional triamcinolone with or without grafts improved the appearance of these lesions.

The aim of the present study was to compare the structural composition of the gingiva of dogs which had not previously suffered from inflammation with that of gingiva which for 6 months had been inflamed, but subsequently healed. The experiments were carried out in eight dogs. After weaning, the dogs were daily subjected to tooth cleaning. When the animals were 10 months old a clinical examination was carried out after which the dogs were randomly distributed into two groups, A and B. Immediately after the clinical assessments, gingival biopsies were obtained from the premolars and molars of the dogsof Group A. The dogs of Group B were allowed to accumulate plaque during a 6-month period after which the examinations were repeated and biopsies were sampled from predetermined areas of the dentition. Following biopsy the remaining teeth of the dogs of Group B were scaled. During the subsequent 6 weeks, the animals were daily subjected to tooth cleaning. The examinations were repeated and biopsies sampled on days 4, 7, 14, 21, 28 and 42. The biopsy material was subjected to morphometric analysis. The resuls showed that it is possible to shift a chronically inflamed gingiva into one which, from a clinical and structural point of view, is almost identical to a gingiva which has never been exposed to gross plaque accumulation. This shift was achieved by elimination of calculus and plaque and by the institution of a careful, daily practiced plaque control program. During healing, the inflammatory cell infiltrate in the connective tissue below the junctional epithelium gradually disappeared and became replaced by collagen. In comparison to inflamed gingiva during healing, the leukocyte content of the junctional epithelium was reduced, whle ee peg formations remained. In the connective tissue papillae beneath these rete pegs, vessels could be recognized. This gave the connective tissue of the healed gingiva a higher vascular content thatn that of a gingiva which had not previously suffered from inflammation.

Vulval lichen sclerosus (L.S.) has been assessed clinically, colposcopically, and histologically to ascertain the suitability of including this condition in the nomenclature proposed by the International Society for the Study of Vulval Disease (I.S.S.V.D). In many cases the macroscopic appearance of lichen sclerosus is characteristic, but this is not always the case. Histologically, the appearances of the dermal hyaline change, the reduction in the length and the number of rete pegs, to a lesser extent thinning of the dermis and sometimes thinning of the epidermis are characteristics. The presence of dermal inflammatory cells and changes in the thickness of the keratin layer are, however, much more variable. Exact measurements of the various layers of the vulval skin are not necessary in the routine assessment of lichen sclerosus. The present study justifies the inclusion of lichen sclerosus on histological criteria in the I.S.S.V.D.'s nomenclature.

Clinical, histological and electron microscopic studies were performed on 4 rhinoscleroma patients with concomitant skin lesions in the upper lip, dorsum of the nose and nasolacry-mal sac area. The skin lesions were treated locally. One of the patients was followed up to 16 years. Histologically, the skin lesions showed downward prolongation of the rete pegs. Deep in the dermis, vacuolated Mikulicz cells surrounded by lymphocytes and plasma cells were found. By electron microscopy, numerous small vacuoles containing fine granular material were seen inside Mikulicz cells. A limited number of bacilli were found inside and outside these cells. Two clinical entities of rhinoscleroma are observed in Egypt, an active granulomatous type with possible extranasal extension, and a less active intranasal type with limited mucosal lesions. The skin lesions in rhinoscleroma were found to have an unpredictable course.

A case of cyclosporine-induced gingival overgrowth is presented. Overgrown and inflamed gingivae were noted at several sites in the mouth of a patient taking cyclosporine following a renal transplant. These were associated with areas adjacent to heavy plaque and calculus deposits on the teeth. Histological examination of the overgrown tissues revealed fibro-epithelial changes characterized by elongated rete pegs, myxomatous degeneration of the connective tissue associated with dense infiltration of plasma cells and lymphocytes. The fibroblasts from normal and overgrown sites were studied in vitro. Fibroblasts from the overgrown tissue proliferated at a slower rate and produced slightly less protein than the cells from normal, healthy gingival sites. These features reflect a site-specific alteration in fibroblast activity and indicate that the lesion is related to local factors exacerbated by cyclosporine therapy.

The purpose of this study was to describe clinical, stereomicroscopic and light microscopic findings for fissured tongue in 17 patients and compare them with 17 normal controls. Clinical symptoms were found in 13 of 17 patients who complained of scoreness of the tongue. Usually the symptoms lasted more than 3 years. In 15 cases, fissures involved the entire tongue, while in 2 cases, only the edges of the tongue were affected. In all patients, papillae of varying sizes were found in the area of fissures. The papillae were easily noted using stereomicroscopy on fixed-tissue specimens, but could also be seen with the naked eye during careful clinical examinations. Light microscopic studies indicated that the number of inflammatory cells was far greater in the mucosa of fissured tongues than in normal tongues, and this inflammation was not confined only to the fissures. The rete pegs of the epithelium were longer in fissured tongues than in normal tongues, 800 (+/- 79) micron and 620 (+/- 69) micron, respectively, (p less than 0.001). The lamina propria was also thicker in fissured tongues than in normal tongues, 390 (+/- 74) micron and 170 (+/- 61) micron, respectively, (p less than 0.001). In normal tongues, keratohyaline granules were observed in the filiform papillae around the area of hairs but these granules were absent in fissured tongues.

Verruciform xanthoma is a rare, granular, plaque-like lesion which occurs on mucosal surfaces and is characterized by acanthosis with xanthoma cells in the dermis between rete pegs. A case of verruciform xanthoma is reported which occurred on the sacral region in a patient with recessive dystrophic epidermolysis bullosa (RDEB). Electron microscopic studies suggested that many of the xanthoma cells were fibroblasts whose vacuolated appearance was expressed in cell culture and persisted for several passages. The occurrence of a verruciform xanthoma in a patient with severe recessive dystrophic epidermolysis bullosa suggests that repeated epidermal and/or dermal damage gave rise to a reactive process involving the formation of lipid-laden cells.

Observations relating to two skin wounds covered with a mesh graft 4 and 9 months previously are described and discussed. The histological findings, particularly those relating to revascularization, are reported in detail. These confirm that, as is to be expected, the skin-grafted sites showed preservation of essentially normal vascular and histological structure in the graft, while in the intervening slits the appearances resemble those of healing by cicatrization with flattened epithelium having no normal rete pegs, no epidermal adnexia, and subjacent poorly vascularized scar-tissue showing evidence of contracture.

The presence of serotonin in the Merkel cells of pig snout epidermis was investigated by the peroxidase-antiperoxidase immunohistochemical technique. Serotonin-like immunoreactive Merkel cells were found in groups located at the base of epidermal rete pegs and in the external root sheath of sinus hair follicles (vibrissae). Immunoreactivity was stronger on the basal side of the Merkel cells, where dense-cored granules are most numerous. Neither the nerve terminal associated with the Merkel cell nor the neighbouring epidermal cells were immunostained. These results are the first evidence of serotonin-like immunoreactivity in mammalian Merkel cells. The fact that immunoreactivity is strongest in those parts of the Merkel cells with the highest granule density suggests that in these cells serotonin is probably localized in the dense-cored granules.

The present study documents the characteristics of innervation of the rhinarium or hairless rat snout skin by light and electron microscopy. The outer glabrous surface is covered with a stratified squamous epithelium that forms both rete pegs and rete ridges, the latter on the inferior border near the philtrum. The glabrous skin contains numerous presumptive epidermal and dermal free nerve endings (FNE's), Merkel terminals at the base of the rete ridges and pegs, and simple, nonencapsulated corpuscles. A second region of dense innervation, found on an elevation of the inner wall of the vestibule, contains similar components of innervation, with the exception that no Merkel terminals were identified. Since no Merkel terminals were present in this area of the vestibule, intraepidermal as well as dermal FNE's could be identified with certainty. This skin is covered by a thin squamous epithelium overlying dense connective tissue. The simple corpuscles are similar to those in the rhinarium, as well as resembling those described in other species. FNE's were frequently observed intimately associated with simple corpuscles. Several examples of large FNE's with two to three layers of cytoplasmic lamellae were found, suggestive of transitional forms between FNE's and simple corpuscles. Thus, the pattern of sensory innervation in the glabrous rat snout skin is similar to that found in other furred species described to date, but in addition, the sensory innervation of ridged skin in the rat also resembles that of epidermis organized into rete pegs. This dense sensory innervation may be correlated with whisking behavior of the predominantly nocturnal rat.

The twenty-sixth case of verruciform xanthoma is reported. The clinical and light microscopic findings in this case are similar to those previously described of a shaggy, parakeratin-covered, pebbly, or verrucous surface and elongated rete pegs which extend a uniform depth into the underlying connective tissue. Large “foam cells” or xanthoma cells filled only the connective tissue papillae between the epithelial pegs. The 1.5 by 4 cm. lesion in our patient is the largest verruciform xanthoma reported to date and is the first to be reported in a black person.

Healing of standardized, excisional wounds in the rat palate has been studied in 40 rats for a period of 3 weeks. The excisional wounds were made with a specially constructed biopsy instrument with a diameter of 3 mm. The soft tissue was removed by sharp dissection and uncovered bone tissue was left for secondary healing. 5 rats were killed at 0, 1, 3, 5, 7, 10, 14 and 21 days after the surgical procedure. Photometric measurements were made of the wound at the different control times and serial sections from blocks including the palate, alveolar process and teeth were subjected to light-microscopical examination. Clinical healing was completed within 3 weeks. Photometric measurements showed an almost 50% reduction of the defect between the 7th and 10th days. Histological examination initially revealed a pronounced inflammatory reaction both in the sub-epithelial connective tissue and in the haversian canals of the bone tissue. The epithelialization progressed from the wound borders, the epithelial cells trying to avoid interference with the inflammatory cell infiltrate. Reduction of the wound surface proceeded by contraction of the wound margins as well as by epithelial cell migration. Empty osteocyte lacunae in the surface layer of the bone tissue beneath the wound and the presence of small nectrotic bone fragments indicated that damage to the bone tissue had occurred during the exposure period. After 3 weeks, the defect was completely covered with epithelium although epithelial rete pegs had not yet developed in the central part of the former defect.

The aging process represents a time-dependent deterioration in the ability of the individual to respond effectively to environmental or internal stimuli; it affects all organ systems, including the skin. Morphologically, major gross aging changes of the skin include roughness, wrinkling, laxity, uneven pigmentation, and a variety of proliferative lesions. The most prominent histologic features associated with cutaneous aging consist of flattening of the dermoepidermal junction with effacement of both dermal papillae and epidermal rete pegs, 1 atrophy of the dermis, 2 and loss of epidermal appendages. 3 Physiologic skin processes that decline with age include proliferative 4,5 and repair capability, 7 barrier function, 8 response to external stimuli, 9,10 dermo-epidermal adhesion, 11 vitamin D production, 12 and, as detailed below, immune function. Understanding of age-related alterations in the immune competence is relevant to understanding the pathogenesis of various diseases associated with aging.

THE EFFECT OF HYDROMASSAGE ON CAPILLARY STRENGTH Kozam, G. N.Y. State Dent. J., 39:551, November, 1973. Forty subjects in good general and periodontal health were tested by using a capillary resistometer to apply suction stress to tissue surfaces at —100, —200, and —300 millimeters of mercury for one minute. Petechiae in a 3 cm. diameter were counted. The test regions used were the antecubital skin of both arms and the lower labial mucosa. The first 4 weeks were used for pre-experimental baselines on the right side of both regions and pre-control baselines on the left. Patients were in­ structed to use a Water Pik spray to their right side areas for 4 minutes. When the hydromassage was used, a rapid decrease in the number of petechiae was demonstrated indicating an in­ creased capillary resistance to rupture to suction-stress tests by a physiologic mechanism. 100 Bergen St., Newark, New Jersey 07103. MASSIVE GINGIVAL HYPERPLASIA PRECEDING DENTAL ERUPTION IN I-CELL DISEASE Galili, D., Yatziv, S., and Russell, A. Oral Surg., 37:533, April, 1974. I-cell disease is a rare condition, found in infants, which is characterized by severe shortness of stature, early psychomotor retardation, congenital dislocation of the hip, inguinal hernia, and facial and skeletal anomalies. Hyperplasia of the gingiva is usually seen by 6-18 months along with variations in the facial configuration. Diagnosis is based on clinical signs and both enzymatic and tissue analyses. The tissue defects resemble those of the "storage" disorders, suggested to be of combined lipid and mucopolysaccharide metabolic groups, and culture of fibroblasts shows the cytoplasmic inclusion which are charac­ teristic of the disease. The disease probably represents the homozygous state of a recessive mutation, but the pathogene­ sis is not known. The reported case is that of a 12-month-old Arab boy, whose parents were first cousins, who presented with all of the aforementioned symptoms. The hyperplastic gingival tissues were firm, hard, and somewhat elastic, with no signs of inflammation. Radiographs showed the tissue to be com­ pletely covering otherwise erupted teeth. The posterior regions of the tissue occluded, while there was an "open-bite" an­ teriorly. The enlargement of the gingiva, combined with the normal size of the tongue reduced the volume of the oral cavity which interfered with breathing and feeding. Histologic examination revealed normal stratified squamous epithelium, with a slight elongation of the rete pegs, and an underlying connective tissue layer consisting of dense collagen and a slight chronic inflammatory cell infiltration. Department of Oral Di­ agnosis, Oral Medicine, and Roentgenology, The Hebrew Uni- versity-Hadassah School of Dental Medicine, P.O.B. 1172, Jerusalem, Israel. HEMORRHAGE AFTER ORAL SURGERY: A N ANALYSIS OF 103 CASES Jensen, P. S. Oral Surg., 37:2, January, 1974. A study was done of 103 patients consecutively treated for postoperative hemorrhage and a control group of 103 patients in the clinics who consecutively underwent the same treatment as the experimental group, but without developing postopera­ tive hemorrhage. The majority of the patients were in the 16- to 30-year old range, with a better than two to one (73:30) ratio of males to females. The most common site of bleeding problems was the lower third molar area, but after periodontal surgery, bleeding was more common from the maxilla. A statistically significant high frequency of earlier postsurgical bleeding episodes suggested that certain oral surgery patients have a tendency to postoperative hemorrhage without display­ ing hematologic values characteristic of any known hemor­ rhagic diathesis. In the remainder of the patients, bleeding was usually of local origin, with a high frequency of mucosal laceration, suggestive of inadequate surgical techniques. Dental Department, University Hospital, Blegdamsvej 9, DK 2100, Copenhagen, Denmark. PERIODONTAL DISEASE, BACTERIA, AND PULPAL

Verruciform xanthoma is a non-tumorous lesion of unknown etiology and uncertain nature, first described by Shafer in 1971.Histologically the characteristic features of the lesion are the presence of rete pegs extremely elongated and large, swollen foam cells or xanthoma cells.This paper presented the case of an 80-year-old female with a lesion at the right lateral margin of the tongue. Histochemical and immunohistochemical detections were also made, and the origin of histiocytes as to foam cells were discussed. In addition the reports concerning it in Japan were reviewed.

Eighteen biopsies of the oral mucosa of northern Thai hilltribe betel chewers were studied histologically and by transmission and scanning electron microscopy (TEM, SEM). Clinically, varying stages of epithelial atrophy and one case of submucous fibrosis were observed. Histologically, epithelial atrophy with marked reduction of the rete pegs, hyperortho- and/or parakeratosis, and subepithelial edema and inflammatory changes were the prominent findings. On the ultrastructural level, cytoplasmic projections of the basal cells into the subepithelial stroma were seen. The basal membrane frequently revealed gaps; the interepithelial space was widened and unusual microvilli were observed on cell surfaces (SEM). Intercellularly, cristalloid material of unknown origin was also seen. The subepithelial connective tissue was characterized by dense bundles of collagen fibres adjacent to which masses of amorphous material were located. While some of the ultrastructural findings in the epithelium of betel chewers are indicative of early dysplastic changes, the nature of the juxta-epithelial stromal alterations is still unknown. Current hypotheses regarding the etiology of oral submucous fibrosis are briefly discussed.

In the newborn rat, innervated Merkel cells were observed in the epidermis of the back and belly next to the tylotrich follicles. Small Haarscheiben could be seen on the belly at birth but were not visible on the back until 10 to 13 days postnatally. The Haarscheiben primordia on the back of the newborn where Merkel cells were found were 95 μm in diameter on the average and were surrounded by epidermal rete pegs. By 13 days, the diameters of the Haarscheiben on the back averaged 208 μm, which is similar to the adult. Haarscheiben on the belly also increased in diameter during this period, but throughout were larger than those on the back. Special cells sharing the morphologic features of both keratinocytes and Merkel cells were found in the epidermis of newborn and 13-day-old Haarscheiben. Similar cells in adult Haarscheiben, which have been called transitional cells, have clumps of tonofibrils in their cytoplasm like keratinocytes, as well as dense-cored granules like those in Merkel cells. From 0 to 13 days after birth, the nerve endings on the Merkel cells and transitional cells were filled with clear-cored, synaptic-sized vesicles. Similar vesicles found in adult nerve terminals were distinctly less concentrated. The neuronal membranes in adult and newborn rats had thickened regions apposed to the Merkel cells. However, the clear-cored vesicles were not directly associated with these areas.

The aims of the present study were to establish normal gingiva in dogs, to characterize the clinical conditions prevailing and to stereologically describe the structural composition of the normal gingival tissues. Three beagle dogs were subjected to regular oral hygiene procedures during 15 weeks. Measurements of gingival fluid flow and the amounts of crevicular leukocytes served to clinically assess the gingival conditions. Semi-and ultrathin sections from biopsies of normal buccal gingival tissues from premolars were subjected to stereologic analysis based on morphometric point counting procedures. Gingival normality was achieved in two of the dogs. The normal gingival tissue in these dogs was characterized clinically by abscense of gingival fluid flow and by a minute amount of crevicular leukocytes. A gingival sulcus was most often absent. The junctional epithelium was without rete pegs, and the entire gingival connective tissue was densely filled by homogeneous collagen fiber bundles. A few isolated inflammatory cells were present in the junctional epithelium and the adjacent connective tissue. No clusters of inflammatory cells forming an infiltrate could be observed. Stereologically, the gingival tissue comprised 48% epithelium and 52% connective tissue. The junctional epithelium occupied 10% of the gingival tissue and included a fraction of 2.8% occupied by leukocytes. The latter by volume comprised 50% neutrophilic granulocytes and mononuclear cells each. The connective tissue was composed of 67% collagen fibers, 14% free cells and 19% residual tissue. The composition of the connective tissue adjacent to the junctional epithelium differed somewhat from that of more central connective tissue fractions.

The gingival basement membrane antigens, Type IV collagen, bullous pemphigoid antigen and epidermolysis bullosa acquisita antigen were studied by indirect immunofluorescence in 11 gingival specimens from patients with periodontitis and 2 normal gingival specimens. In the normal control gingival specimens, the antigens were all present and stained with a continuous linear pattern. In periodontitis, alterations occurred in the gingival basement membrane antigens in the apical portion of the pockets. These included thinning, interruptions, partial or complete absence involving one or more rete pegs and fragmentation. These alterations may result form the disease process or play a role in the pathogenesis.

The foot sole epidermis of the fore and hind feet of the adult mouse contains an acidic (type I) mRNA-encoded 73-kDa keratin polypeptide which cannot be detected in any other skin site of the mouse integument. Western blot analysis using an antibody specific for the 64-kDa keratin 9 of human and bovine callus-forming epidermis [A. C. Knapp et al. (1986) J. Cell Biol. 103, 657-667] demonstrates that the 73-kDa keratin represents the murine analog of keratin 9 of man and cow. Concomitant investigations in two related rodent species indicate that the size of this keratin varies more among species than that of any other orthologous keratin. Histological examination of adult mouse foot sole skin reveals an extremely thick and undulated epidermis covering the apical portion of the six footpads, whereas the epidermal-dermal junction of the lateral walls of these nodular protuberances as well as that of the remainder of the foot sole skin is essentially flat. If sections of adult foot sole skin are investigated by indirect immunofluorescence with the keratin 9-specific antibody, intense cytoplasmic staining is restricted to the apical rete pegs of the footpad epidermis in which virtually all suprabasal cells express keratin 9. However, we also observed keratin 9-negative cell columns ascending straight above the tips of the dermal papillae and separating the keratin 9-positive rete pegs from each other. At the transition from the strongly undulated apical epidermis to the flat epidermis of the lateral walls of the footpads, keratin 9-positive cells loose their coherence and gradually disappear toward the inter-footpad epidermis. This intimate relationship between the morphogenesis of epidermal ridges and inter-ridges and the expression of keratin 9 is also visible in foot sole epidermis of neonatal mice. Here we observed the appearance of keratin 9-positive suprabasal cells concomitant with the onset of pronounced folding of the apical footpad epidermis by about Day 3 after birth. Our findings confirm the view that the expression of keratin 9 is characteristic of a highly specialized pathway of epidermal differentiation. We propose a hypothesis for keratin expression in skin sites which are subject to pronounced mechanical wear and tear.

Oxytalan fibres in hyperplastic gingival papillae from 12 young epileptics who had been treated with sodium diphenyl-hydantoin were studied with modifications of Fullmer and Lillie's (1958) and Loe and Nuki's (1964) staining methods. These fibres were compared with the fibres in clinically normal gin-givac and in tissue from fibrous epulides. Fibres reacting with peracetic acid-aldehyde fuchsin (i.e. oxytalan fibres) were present throughout the connective tissue and were especially numerous near the surface epithelium and in areas of inflammatory infiltration. The oxytalan fibres were especially prominent along the junction with epithelium, between the rete pegs and in the deeper connective tissue near bone where they tended to be arranged in large parallel bundles. In cases of fibrous epulis, however, there were very few oxytalan fibres in the connective tissue adjacent to the surface epithelium. It is concluded that the connective tissue performs an important supportive function to the epithelium in gingival hyperplasia, and is of special importance in the genesis of gingival hyperplasia in patients under treatment with sodium diphenyl-hydantoin.

SUMMARY.— Single psoriatic lesions were analysed planimetrically and auto-radiographically after 3H-thymidine labelling. The results indicate maximum alterations of epidermis and papillary body in the centre of a lesion. Epidermal volume values are elevated at the periphery while the papillary body is still normal. After stripping, the proliferative activity of the peripheral epidermis increases in proportion to epidermal volume, while no stimulatory effect can be exerted in the centre of a lesion. Comparison of several lesions reveals large differences for volume values and between single rete pegs for 3H-thymidine labelling. The role of an epidermal defect in evoking the changes is discussed.

This paper describes a survey of 198 cases of oral verrucous carcinoma reported in the literature and a study of a further 15 personally-observed cases. Elderly Caucasoid males are most frequently affected, although in the South African group there were 10 females and 5 males. The lesion, which classically has a verrucous surface, may be small or more extensive. The cheek mucosa and the alveolar mucosa/gingiva are the sites most commonly involved. Sometimes more than one area is affected in the same patient and the tumor may be associated with other lesions such as leukoplakia, pseudo-epitheliomatous hyperplasia and frank carcinoma. The etiology is uncertain but tobacco usage in any form appears to be implicated. The tumor is locally invasive and 6 of our series of 15 recurred after surgical removal. It does not metastasize unless it undergoes anaplastic transformation, which it frequently does if treated with radiotherapy. The correct treatment is therefore wide surgical excision. Histologically, there is a typical abrupt margin. The tumor has surface papillary projections and infiltrating broad, blunt rete pegs which form a “pushing margin”. The epithelium is generally well-differentiated but there may be a high mitotic index and there may be an appearance of epithelial atypia if the epithelium is inflamed. Keratin is usually present on the surface and in the crevices of the deep invaginations but may be absent from tumors involving non-kcratinizing surfaces.

Ovariectomies were performed on 8 squirrel monkeys. Four of the animals received 0.1 mg estradiol benzoate intramuscularly 3 times per week for 4 months. One hour prior to sacrifice all animals received H3-thymidine. Sections of vagina, buccal mucosa and gingiva were processed for hematoxylin and eosin staining and autoradiographs. Measurements were made of the basemined membrane/mm of surface length, the number of basal cells/mm of basement membrane determined and a labeling index for basal cells established. The animals which had received estradiol benzoate exhibited a thick vaginal epithelium in contrast to the other animals which showed a thin and often ulcerated epithelial covering. The vaginal epithelium of the estrogen treated ovariectomized animals had longer rete pegs, fewer basal cells/mm of basement membrane and a higher labeling index than those animals not receiving estrogen. The epithelium of the buccal mucosa was significantly different in the same direction as the vagina by all three criteria. The gingival epithelium showed no significant differences by two of the three criteria.

The finger- and palm prints of 105 adults and 56 children with celiac sprue, and 33 patients with dermatitis herpetiformis, were studied. Epidermal ridge atrophy of varying degree was a characteristic feature of adult celiac sprue, present in 90% of patients, but was not a feature of childhood celiac sprue nor of dermatitis herpetiformis, and it improved on treatment with a gluten-free diet. Six of the 1310 control subjects had epidermal ridge atrophy, and 5 of these had liver disease. Postmortem histology of fingertip skin in 4 patients with epidermal ridge atrophy (3 celiac patients, 1 patient with liver disease) showed dermal atrophy with flattening of the rete pegs. Histology was normal in 70 control subjects and 2 celiac patients who did not have epidermal ridge atrophy. It is suggested that finding epidermal ridge atrophy in an adult should alert the physician to the possibility of celiac sprue.

Near-infrared confocal microscopy is a new tool that provides skin images in vivo, with high resolution and contrast at a specific depth. Regional variations in live human skin viewed by confocal microscope have not been studied so far. In vivo reflectance confocal microscopy was performed in 10 adults (eight males, two females) of various skin phototypes. Six topographic sites were studied in each subject: forehead, cheek, inner and outer forearm surfaces, lower back and leg. Epidermal thickness at suprapapillary epidermal plates and rete pegs was measured during real-time imaging and the number and diameter of epidermal keratinocytes in each epidermal cell layer as well as the characteristics of dermal papillae were defined from the grabbed images. Stratum corneum appeared brighter in sun-exposed than in sun-protected areas and particularly pronounced in heavily pigmented individuals. The epidermal thickness at rete pegs, but not the suprapapillary epidermal plate, was greater in sun-exposed areas than in sun-protected sites except forearm flexor surface. The en face numerical density of granular keratinocytes is greater on the face as compared with all other sites, whereas the surface density of spinous keratinocytes is greater on sun-protected sites. Additionally, the number of basal keratinocytes per millimeter length of dermoepidermal junction is greater in sun exposed areas. Interestingly, the dermal papillae shape varies and their sizes increase in circumference from sun-exposed to sun-protected sites, as observed at a specific depth below the stratum corneum. In summary, our results demonstrate that near infra-red reflectance confocal microscopy is a feasible tool for microscopic analysis of skin morphometry in vivo.

Gian keratoacanthoma on the inner surface of the prepuce was observed in a 45-year-old man. First symptoms had appeared three months earlier. The tumour was surgically removed. The main histological features of the tumour were enormous, but relatively regular, acanthosis of rete pegs revealing no similarity to the squamous-cell carcinoma, and an exclusively parakeratottic eleidine-containing central plug. The name parakeratoacanthoma is suggested for this type of tumour.

The mouse-mutant sex-linked anaemia (sla) suffers from iron-deficiency anaemia due to a defect of iron absorption from the gut. The lingual epithelium of anaemic mice was significantly thinner and less well-differentiated into papillae and rete pegs than normal when taken from the anterior dorsum but not from the posterior dorsum. The mutant may be a useful experimental model in which to study more detailed effects of iron deficiency on the oral mucosa.

Two cases of verruciform xanthoma of the vulva are described. This rare lesion, previously reported to occur only in the oral cavity, is characterized by a verrucous epithelial proliferation accompanied by xanthoma cells distributed exclusively in the papillary dermis. The histologic features of the lesion are diagnostic and include (1) regular acanthosis in which the rete pegs extend to a uniform level into the dermis; (2) hyperkeratosis with parakeratosis often extending deep into the rete pegs and manifesting a massive neutrophilic infiltrate; (3) hyalinization of the collagen and infiltrates of xanthoma cells that are restricted to the papillary dermis between the rete pegs. Additionally, a lichenoid inflammatory infiltrate is seen at the periphery of the verrucous lesions, and in one case this has the pattern of classic lichen sclerosus. Verruciform xanthoma must be differentiated from verruca vulgaris, condyloma acuminatum, granular cell tumor with pseudoepitheliomatous hyperplasia, and verrucous carcinoma.

The innervation of the vermilion border and mucosa of the monkey lip have been studied by light and election microscopy. Meissner corpuscles are present at the junction between hairy skin and vermilion border usually high in the dermal papillae, tightly abutting the overlying basal layer of the keratinized squamous epithelium. These Meissner corpuscles resemble those described in primate glabrous skin and are characterized by the presence of stacks of lamellae interposed between loops of the terminal axon. The lamellae are cytoplasmic extensions of specialized Schwann cells referred to as lamellar cells. One to three myelinated axons, 2–4 μm in diameter, innervate a single Meissner corpuscle. Coiled simple corpuscles, innervated by 1–3 myelinated axons, 3–5 μm in diameter, are characteristic of the non-keratinized portion of vermilion border and oral mucosa. The terminal axons in simple corpuscles are enveloped by circumferentially arranged cytoplasmic lamellae. Small terminal axoplasmic spikes protrude into spaces between the cytoplasmic lamellae in both Meissner and simple corpuscles. Cytoplasmic lamellae in both receptors are characterized by the presence of numerous pinocytotic vesicles. The lower parts of Meissner as well as simple corpuscles are encapsulated by perineurium and these perineural epithelial cells have incomplete basal lamina on both sides of their flattened cytoplasm. In contrast, corpuscles that are present high in the dermal papillae have scant perineural capsular elements and instead have fibroblast-like cells demarcating the inner core of the corpuscle from the general connective tissue compartment. Endoneural fibroblasts are a constant component of all corpuscular receptors. Tactoids of fibrous long-spacing collagen are present in the endoneural connective tissue of these sensory corpuscles. The vermilion border has 10–20 corpuscular receptors per mm 2 of surface area. Tastscheiben consisting of clusters of Merkel cells and their associated axons are present in the basal layer of rete ridges and rete pegs throughout the hair skin, vermilion border, and oral mucosa of the primate lip. Free nerve endings (FNE's) have been identified using cytologie criteria described previously 54 . FNE's in the vermilion border and mucosa often establish intimate contact with the basal lamina and/or basal cells of the epithelium. FNE's can also be identified in dermal papillae that contain Meissner and/or simple corpuscles. Ruffini nerve endings are not present in dermal papillae. This relatively dense sensory innervation can be correlated with the known tactile sensitivity of the lip in terms of twopoint as well as force thresholds and expanded areas of thalamic and cortical representation. The innervation of glabrous skin resembles that of hairy skin with Meissner and simple corpuscles of glabrous skin being equivalent to lanceolate terminals of hairy skin. The other sensory terminals of each type of skin are identical. Hairs provide an anatomical substrate for multiple afferent terminals, and rete ridges/dermal papillae are the equivalent structural unit in glabrous skin. Each cutaneous anatomical site can be multiply innervated, and this afferent information is processed centrally over multiple parallel ascending systems.

The sensory organization of the cat rhinarium has been investigated. Individual rete pegs were found to contain a triad of receptors comprising free nerve endings ascending in the peg to terminate in close proximity to the skin surface, a basally situated layer of Merkel corpuscles, and an abundance of encapsulated receptors lying at the base and to one side of the rete peg. Neither the Merkel corpuscles nor the encapsulated receptors were evenly distributed. Merkel corpuscles were more abundant dorsally; ventrally they were fewer and asymmetrically arranged within individual rete pegs. The encapsulated corpuscles were more evenly distributed, but dorsally they were consistently present as encapsulated clusters of up to nine corpuscles.

The aim of this study was to obtain a detailed description of the histology of normal vulval skin in relation to age and position on the vulva. At all positions on the vulva, the thickness of the keratin, epithelial and dermal layers increased during the reproductive years. The number of rete pegs per unit area was maximal when the epithelial layer was thickest. After the menopause, a slow and progressive atrophy occurred. Mitotic activity in the epithelial layer was low but maximal during the reproductive years. The presence of dermal hyaline change was rare.

Histopathological, histochemical and ultrastructural findings of an extraosseous ameloblastoma occurring in an 89-year-old woman are reported. Rete pegs of the gingival epithelium covering the lesion showed marked extension into the lesion, and direct continuity between the extended rete pegs and tumor follicles was evident. Ultrastructural examination showed that the rete pegs gradually became transformed into double-stranded epithelial cords as they elongated deeply, and that the ends of these epithelial cords gradually became transformed into tumor follicles. These findings suggest that the potential for differentiation is maintained in the basal cells of the gingival epithelium throughout life, and can be triggered by unknown stimuli. The ultrastructure of the tumor follicles was similar to that of intraosseous follicular ameloblastoma, but was different from that of cutaneous basal cell carcinoma. Histochemical staining for keratin protein revealed that the central cells of tumor follicles and the covering epithelium were positive, whereas the peripheral cells of tumor follicles and the elongated rete pegs were negative.

The influence of the sulcular environment on the keratinization of the outer surface gingival epithelium was tested in three young adult Rhesus monkeys. A total of 40 mucoperiosteal flaps were raised, and inverted so as to bring the outer surface epithelium in contact with the tooth, and were sutured. The experimental time intervals varied from 1 hour to 60 days. The monkeys received H3 thymidine 1 hour prior to sacrifice. The material was prepared for histologic and radioautographic evaluation. Results indicated that the outer surface epithelium changes its morphology to a nonkeratinized epithelium devoid of deep rete pegs when in close contact with the tooth, resulting in the anatomical characteristics normally seen in sulcular epithelium. It is concluded that the sulcular environment has the capability of controlling the keratinizing potential of the outer surface gingival epithelium. It is further suggested that the constant irritation of bacterial plaque and its products may be responsible for the premature desquamation of the sulcular epithelium which in turn might not allow its full differentiation.

The distribution and ultrastructure of Merkel cells in the hard palate was investigated in the squirrel monkey (Saimiri sciureus) after fixation by vascular perfusion. Merkel cells were clustered at the base of the epithelial rete pegs of the hard palate. They were characterized by concentrations of dense-cored granules and closely associated intraepithelial nerve endings. Numerous spiny processes extending from the Merkel cell were intercalated with adjacent keratinocytes, probably serving to detect and amplify movement of adjacent cells. These spiny processes contained a rigid core of parallel microfilaments which were interrelated with cytoplasmic filament bundles located beneath the cell membrane. Transitional cells containing dense-cored granules and well developed tonofibrils appear to be related to both Merkel cells and keratinocytes. The findings of this study suggest that Merkel cells are highly adapted for detection of movement in adjacent keratinocytes, as well as movement of the epithelium with respect to the underlying connective tissue.

"Leukokeratosis nicotina glossi" or "smokers' tongue" is a homogeneous leukoplakia with evenly distributed pin-point hemispherical depressions. Histologically, there is a loss of glossal papillae, hyperkeratosis, acanthosis and the formation of large drop-shaped rete pegs with central clefting and occasional parakeratotic plugging. Mitotic activity and atypia are not marked and there is no evidence of Candida species infection. In some respects the lesion histologically resembles verrucous carcinoma but, unlike that condition, papillomatosis is not clinically noticeable and an invasive "leading edge" is not apparent. All but one of the subjects in which the lesion was seen were men, all had concurrent leukokeratosis nicotina palati and two gave histories of laryngeal carcinoma.

Verapamil-induced overgrowth was most prominent in the anterior regions and interproximal areas associated with plaque retention. Despite periodontal therapy, overgrowths recurred 1 month after gingivectomy. Discontinuation of the drug resulted in regression of the overgrowths. Histologic findings showed inflamed connective tissue covered by an acanthotic, thickened oral epithelium with long rete pegs containing dyskeratotic pearls. The proliferation rate and protein and collagen production of fibroblasts from the overgrowth sites were markedly lower than in the control cells cultured from healthy gingiva. Incubation of fibroblasts in the presence of verapamil reduced protein and collagen synthesis.

The buccal and lingual gingival tissues in the vervet monkey were compared. Blocks of fresh tissue, consisting of mandible and associated soft tissues, were prepared for histological examination. Coronal and transverse sections, 7 and 25 μm thick, were cut through the full thickness of the mandible and stained with haematoxylin and eosin, picromallory and a variety of elastic stains. Photomicrographs of step serial sections were enlarged to standard magnification for histometric analysis. The buccal epithelium is thicker and shows a greater degree of keratinization than the lingual epithelium. The rete pegs are more prominent and penetrate deeper into the lamina propria on the buccal aspect. There appears to be two sets of elastic fibres in the submucosa on the buccal aspect and only one on the lingual. The buccal elastic fibres consist of a sub-epithelial plexus of fine fibres and a longitudinal set of thicker fibres. The lingual fibres are situated sub-epithelially only. The presence and orientation of the elastic fibres may be associated with the functional demands of flexibility and resiliency on the two epithelia.