bluuebunny/crossref_metadata_2025 huggingface dataset:
A clinical trial of Azelastine in recurrent aphthous ulceration, with an analysis of its actions on leukocytes
Authors: Ueta Eisaku , Osaki Tokio , Yoneda Kazunori , Yamamoto Tetsuya , Kato Itsuki
Published: April 2006

Azelastine (azelastine hydrochloride) was orally administered to 43 patients with recurrent aphthous ulcers (RAU). and its clinical effects and in vitro influence on leukocytes were examined. During at least 6 months after drug treatment, no oral ulcers occurred in 7 patients, and an improvement of the oral condition was exhibited in all except 4 of the remaining patients. The frequency of occurrence of RAU was significantly reduced, from 1.7 ± 0.9 to 0.9 ± 0.5 times month. and ulcer duration and oral irritation were also significantly reduced from 12.5 ± 2.5 and 7.5 ± 2.4 days to 9.8 ± 2.6 and 5.3 ± 2.4 days, respectively. Neutrophils from patients treated with Azelastine generated a suppressed volume of superoxide (O2). Suppression of O2 generation and chemiluminescence by in vitro Azelasline was also confirmed to occur in a dose‐dependent manner. Furthermore, the production of TNF‐α and GM‐CSK in lymphocytes was suppressed in the presence of Azelastine, and the drug protected sheep red blood cells and epithelial tumor cell lines against hydrogen peroxide impairment and hypotonic shock. These clinical and experimental results lead to the conclusion that improvement of RAU by Azelastine depends on the protection of cell membranes and the suppression of leukocyte‐function, including reactive oxygen generation.
The effect of exposure to chlorhexidine gluconate in vitro and in vivo on in vitro adhesion of Candida albicans to buccal epithelial cells from diabetic and non‐diabetic subjects
Authors: Darwazeh A. M. G. , Lamey P.‐J. , MacFarlane T. W. , McCuish A. C.
Published: April 2006

The effect of 0.2% chlorhexidine gluconate on in vitro adhesion of Candida albicans to buccal epithelial cells (BHC) was studied in 12 healthy subjects and 12 patients with diabetes mellitus. Exposure of BFC for one minute with 0.2% chlorhexidine gluconate in vitro, or by rinsing the mouth in vivo, resulted in a significant reduction in candidal adhesion to BHC in both diabetic and non‐diabetic subjects and between both groups. In addition to the known fungicidal effect of chlorhexidine, it also reduces Candida albicans adhesion to oral mucosal cells, a factor of importance in the establishment of candidal infection.
Comparison of a lesion‐inducing isolate and a non‐lesional isolate of Candida albicans in an immunosuppressed rat model of oral candidiasis
Authors: Allen Carl M. , Saffer Aron , Meister Richard K. , Beck Frank M. , Bradway Steven
Published: April 2006

Two distinct strain‐related patterns of organism‐host interaction on dorsal tongue of immunocompetent rats have been identified for Candida albicans: some isolates induce mucosal lesions, while other isolates penetrate the keratin layer hut do not produce a lesion. This study examined the behavior of each of the two types of isolates in a cyclosporin‐immunosuppressed rat model. Groups B (normal) and D (cyclosporin) were orally inoculated with a lesion‐inducing isolate of C. albicans. while a non‐lesional isolate was given to Groups A (normal) and C (cyclosporin). A typical dorsal tongue lesion developed in 4/18 rats in Group B and in 13/16 in Group D (p= 0.00267). No significant difference in infection rate between the normal and cyclosporin‐treated animals was seen for the non‐lesional isolate. The lack of a host inflammatory response associated with the non‐lesional isolate may represent an ecologic advantage for the organism.
Changes in cytokeratins following treatment of hamster cheek pouch epithelia with hyperplastic or neoplastic agents
Authors: Shearer B. H. , Jenkinson H. F. , McMillan M. D.
Published: April 2006

The effects of four different hyperplastic agents and of the carcinogen DMBA on cytokeratin expression in hamster cheek pouch epithelia were compared. Reversible hyperplasia was produced by the application of either oil of turpentine, vitamin A or TPA. No hyperplastic changes were produced by application of EPP. Apart from the transient appearance of a 45 kDa cytokeratin in one group treated with vitamin A. the immunohistochemical staining patterns and immunoblot profiles of cytokeratins from cheek pouches treated with each of the hyperplastic agents were identical to controls. Following application of OMBA, the cytokeralins stained with increased intensity in the spinous and granular cell layers. This was associated with increased amounts of 42 56 kDa cytokeratins and decreased production of 62 75 kDa cytokeratins. Monoclonal antibody AE1 detected a 45 kDa cytokeratin in extracts of DMBA‐treated epithelia that was not detected in untreated epithelial extracts. Monoclonal antibody AE3 detected an additional 54 kDa cytokeratin hand in extracts of DMBA‐treated epithelia. These cytokeratin changes were present in preneoplastic epithelia and maintained in neoplastic epithelia.
Absence of a reservoir of Epstein‐Barr virus (EBV) in normal tongue epithelium
Authors: Miller D. R. , Heard P. L. , Cagle M. P. , DiMaio D. , Ench Y. , Morrison D. G. , Eagan P. A. , Gulley M. L. , Jenson H. B. , Moyer M. P.
Published: April 2006

We examined human tongue epithelium and serum samples at autopsy for evidence of latent Epstein‐Barr virus (FBV) infection. Although clinical serology revealed anti‐HBV antibodies in most sera indicating past FBV infection, we found no Epstein‐Barr nuclear antigen (EBNA‐coding sequences in tongue tissue‐by polymerase chain reaction (PCR). or Epstein‐Barr‐encoded RNA (EBERI) by in situ hybridization. Tongue epithelium does not appear to be a natural reservoir for latent by EBV in immunocompetent hosts
Oral mucosal changes and nicotine disposition in users of Swedish smokeless tobacco products: a comparative study
Authors: Andersson Gunilla , Björnberg Gunilla , Curvall Margareta
Published: April 2006

The purpose of this study was to investigate the uptake and metabolism of nicotine by smokeless (oral) tobacco users and to find out if the less pronounced clinical changes in the oral mucosa in users of portion‐bag packed oral moist snuff (snus) compared with the changes in the mucosa of loose snus users are correlated to exposure and uptake of tobacco constituents. 54 habitual users of smokeless tobacco were selected for the study: 22 loose snus users, 23 users of portion‐bag packed snus and 9 users of chewing tobacco. In accordance with previous findings, less pronounced clinical changes in the oral mucosa were recorded in portion‐hug users compared with loose snus users. The clinical findings observed in the oral mucosa of users of chewing tobacco were leukoedema and slight clinical “snus changes”. The average intake of nicotine (measured as nicotine equivalents excreted during 24 h) for snus users was 35 mg, and was 50% higher for users of chewing tobacco. The average steady‐state saliva cotinine concentration was about 300 ng ml for both categories of snus users, which is similar to that found in smokers, while the average concentration found in users of chewing tobacco was 50% higher. There was a good correlation between saliva cotinine concentration and the 24 h intake of nicotine. The average excretion profile of nicotine was similar in all three groups of smokeless tobacco users, being on average: nicotine 8%, nicotine‐Glca 3%, cotinine 8%, cotinine 9%, 3′hydroxycotinine 42%, 3′hydroxycotinine‐GlcA 19%, nicotine‐N ‐oxide 9%, and cotinine‐N‐oxide 3%. The clinical severity of buccal mucosal changes correlated neither with the markers for exposure (i.e. nicotine and tobacco specific nitrosamines extracted from the tobacco) nor with the biological markers for uptake of tobacco constituents (i.e. nicotine equivalents excreted during 24 h and saliva cotinine concentrations).
The relationship between micronutrient depletion and oral health in geriatrics
Authors: Sweeney M. P. , Bagg J. , Fell G. S. , Yip B.
Published: April 2006

Changes in the oral microbial flora, some of which are related to mucosal disease, have been delected in the elderly, but the causes are not fully understood. This study has examined the possible role of micronutrient depletions in the reduced colonisation resistance and oral infection exhibited by some elderly subjects. The oral health, oral microbiology and micronutrient status of 37 geriatric patients aged 65–91 years (mean 81 years) were examined. Ten of the patients had no oral mucosal disease. Mucosal pathology in the remainder included erythema (27%). denture stomatitis (24%). angular cheilitis (16%) and atrophic glossitis (41%). Those with mucosal pathology had significantly lower serum iron concentrations (P= 0.02). Serum or plasma concentrations of zinc, copper, selenium, C‐reactive protein, transferring, caeruloplasmin, albumin, vitamin A and vitamin E were not significantly different between those with oral disease and those with healthy mouths. Similarly, activity of the selenium‐containing enzyme, red cell glutathione peroxidase, did not differ significantly between the two groups. In both groups, plasma selenium concentrations (82%), red cell glutathione peroxidase activity (47%), plasma zinc concentrations (58%) and albumin concentrations (44%) tended to be below the lower limit of the reference interval. The influence of sub‐clinical infection on these values is discussed.
Immunomodulation by levamisole in patients with recurrent aphthous ulcers or oral lichen planus
Authors: Sun A. , Chiang C‐P. , Chiou P‐S. , Wang J‐T. , Liu B‐Y , Wu Y‐C.
Published: April 2006

The purpose of this study was to evaluate the effect of levamisole on the immune system of patients with recurrent aphthous ulcers (RAU) or oral lichen planus (OLP) in an open trial. Lymphocyte subsets, serum immunoglobulins, and circulating immune complexes (CIC) in patients with RAU or OLP and in normal control subjects were determined by an indirect immunofluorescence (ML) technique with monoclonal anti‐lymphocyte antibodies, by single radial immunodiffusion, and by precipitation with 3% polyethylene glycol, respectively. In addition, the anti‐nuclear antibodies (ANA) and anti‐basal cell antibodies (anti‐BCA) in sera were detected by an IIF technique. We found a significant improvement in clinical symptoms and normalization of the decreased CD4/CD8 ratio in RAU patients after levamisole treatment. Moreover, the decreased CD4/CD8 ratio, which persisted until the remission stage in the untreated RAU patients, reverted to normal m the active late stage in the levamisole‐treated patients. This reversion of aberrant cellular immunity in an earlier stage of the ulcer cycle may explain why RAU patients experience symptom improvement after levamisole treatment. Although RAU patients treated with levamisole for 1 to 3 or 4 months still had higher than normal levels of CIC and serum immunoglobulins, the levels of their IgA and IgM returned to normal values after 4 months of levamisole treatment. The serum ANA detected m 6 patients with RAU and 3 patients with erosive OLP disappeared after 1‐22 months of levamisole treatment. The disappearance of serum anti‐BCA was also observed in 50%, of the anti‐BCA‐positive patients with erosive OLP after 3–13 months of levamisole treatment. These findings suggest that levamisole has modulating effects on both cell‐mediated and humoral immunity in patients with RAU or OLP.
Candidal infection of the gingiva in HIV‐infected persons
Authors: Odden K. , Schenck K. , Koppang H. , Hurlen B.
Published: April 2006

Gingival biopsies were taken from 27 HIV (human immunodeficiency virus)‐seropositive persons with gingivitis or periodontitis and 16 HIV‐seronegative persons with periodontitis. Sections were stained with hematoxylin and eosin or periodic acid‐Schiff. Candidal hyphae and pseudohyphae were found in the para‐keratinized oral epithelium in 7 specimens from the HIV‐infected patient group and in the connective tissue close to the bottom of the gingival pocket in one such specimen. No fungal invasion was found in any of the biopsies from the HIV‐seronegative persons. Candidal invasion was significantly more frequent (P<0.05) in patients with a confirmed history of necrotizing periodontal diseases (5/9) than in patients without known episodes of such diseases (3/18). The most prominent histopathologic changes observed in connection with candidal invasion comprised polymorphonuclear leucocyte infiltration of the oral gingival epithelium and numerous mitoses, some of which were located suprabasally. It is suggested that Candida albicans may contribute to the development of necrotizing periodontal diseases in HIV‐infected persons.
Application of dual parameter analysis in flow cytometric DMA measurements of paraffin‐embedded samples
Authors: Nylander K. , Stenling R. , Gustafsson H. , Roos G.
Published: April 2006

In a comparison of flow cytometric DNA measurements on fresh and para (Tin‐embedded material from primary squamous cell carcinomas of the head and neck region, we discovered that previously undetected aneuploid clones could he detected by dual parameter analysis of cytokeratin and DNA applied to disintegrated cells from paraffin sections. Using this new approach the correlation coefficient between DNA‐indices from fresh and paraffin‐embedded material increased from 0.42.1 to 0.904.
Quantitative cellular and nuclear volumetric alterations in epithelium from lichen planus lesions of human buccal mucosa
Authors: White F. H. , Jin Y. , Yang L.
Published: April 2006

Patients with oral lichen planus lesions may represent a relatively high risk population for subsequent development of oral cancer. Little is known of the relative effects of chronic inflammation and the process of malignant transformation itself on the histological structure of transforming epithelia. We have assessed cellular and nuclear volumes in defined basal and spinous cells from normal buccal mucosa epithelium, from epithelium associated with a non‐specific chronic inflammatory infiltrate and from lichen planus lesions. Normal (N) tissues were obtained from the margins of non‐neoplastic buccal mucosa lesions. Inflammatory (INF) lesions were from areas of the buccal mucosa diagnosed clinically as traumatic irritation without ulceration, and lichen planus (LI) lesions were biopsied from areas exhibiting Wickham's striae. Basal and spinous epithelial cells from normal and pathological human buccal mucosa were measured on haematoxylin and eosin‐stained sections imaged through a video camera using a ZCELL VIDAS analyser and from these measurements, nuclear (VN) and cellular (VCELL) volumes were determined. VN and VCELL derived for both basal and spinous strata were similar in N and INF groups but were almost doubled in the LI group. Comparisons between LI and all other groups were significantly elevated. The effects of the inflammatory infiltrate on the oral epithelium in lichen planus and in non‐specific inflammation thus differ significantly. VN and Vcell may serve as potential discriminators between benign lesions and premalignant lichen planus.
Significance of oral examination in chronic graft‐versus‐host disease
Authors: Hiroki A. , Nakamura S. , Shinohara M. , Oka M.
Published: April 2006

Fourteen patients who received allogeneic bone marrow transplantation (BMT) were examined 100 to 220 days after BMT. Ten out of 14 patients were diagnosed as having chronic graft‐versus‐host disease (cGVHD) in skin, liver, eyes and other organs. These cGVHD patients also had objective evidence of oral involvement. Subjective xerostomia was experienced by 7 cGVHD patients and decreased whole saliva flow was observed in 4 cGVHD patients. However, no patient had a history of parotid swelling or notable abnormality in parotid sialography. Labial salivary glands (LSG) of 9 cGVHD patients showed atrophy and/or destruction in association with diffusely infiltrating lymphocytes. The infiltrating lymphocytes were mainly CD3+ T cells with a predominance of CD8+ cells over CD4+ cells. Lichenoid lesions on the oral mucosa were also observed in 5 cGVHD patients. Thus, this study indicated that oral examination, including LSG biopsy, is useful in the diagnosis of cGVHD.
Type 3 burning mouth syndrome: psychological and allergic aspects
Authors: Lamey P.‐J. , Lamb A. B. , Hughes A. , Milligan K. A. , Forsyth A.
Published: April 2006

A subgroup of patients with burning mouth syndrome was investigated. The clinical history of these patients differed from the norm in that symptoms were intermittent and affected unusual sites. In addition, routine investigations were supplemented with a more detailed psychological evaluation than reported previously and also a possible allergic component was studied by patch testing. The study has shown that this subgroup differs from burning mouth syndrome patients overall in that emotional instability and allergic reactions, particularly to food additives, are of etiological significance and require to be taken into consideration in terms of patient management.
Immunocytochemical localization of bone morphogenetic proteins (BMPs) in salivary gland pleomorphic adenoma
Authors: Hatakeyama Setsuko , Satoh Masanobu , Yoshimura Noriko , Otsu Tadashi
Published: April 2006

The localization of bone morphogenetic protein (BMP)‐1, ‐2, ‐3 and transforming growth factor (TGF)‐β in normal salivary gland and pleomorphic adenoma of the salivary gland has been examined immunocytochemically. Tumor cells with BMP immunostaining in pleomorphic adenoma were associated with some solid cellular and tubuloglandular patterns, and with stellate cells in the myxoid area. In addition, in the chondroid area of three pleomorphic adenomas, chondrocyte‐like cells were positive for BMPs. It is speculated that BMPs secreted by the tumor cells play a role in the formation of the chondroid component in pleomorphic adenoma by inducing some tumor cells, probably neoplastic myoepithelial cells, to differentiate to chondrocytes by metaplastic change. No tumor cells specifically immunostained with TGF‐β were found. TGF‐β was positive in fibrous and hyalinized stroma. In the submandibular gland, only anti‐BMP‐1 antibody specifically reacted to apical portions of degenerated serous acinar cells.
Cytomegalovirus (CMV) and Helicobacter pylori(HP) found in oral mucosal ulcers
Authors: Leimola‐Virtanen R. , Happonen R.‐P. , Syrjänen S.
Published: April 2006

The possible involvement of Cytomegalovirus (CMV) and Helicobacter pylori (HP) in oral mucosal ulcers is suggested by their role in the development of ulceration at other mucosal sites of the gastrointestinal tract. A series of 29 incisional biopsies from 29 consecutive and apparently immunocompetent patients attending the clinic for oral ulceration were examined by routine histopathology as well as by in situ hybridisation (ISH) with biotinylated CMV and HP DNA probes. In 14/29 biopsies, Giemsa staining disclosed spiral bacteria. Six (20.7%) of these 14 Giemsa‐positive samples showed HP DNA on ISH and 3 ulcers (10.3%) contained CMV DNA. In none of the specimens were CMV and HP detected simultaneously. Two of the ulcers containing CMV DNA were found on the labial mucosa and one on the posterior palatal mucosa, whereas all HP DNA‐positive ulcers were located on the buccal mucosa. The results indicate that CMV and HP DNA can be found in separate oral mucosal ulcers in apparently immunocompetent adults.
Inflammatory cell infiltrate associated with primary and transplanted tumours in an inbred model of oral carcinogenesis
Authors: Thomas D. W. , Matthews J. B. , Patel V. , Game S. M. , Prime S. S.
Published: April 2006

This study characterised the nature of the local cellular immune responses associated with an inbred animal model of oral carcinogenesis. Inbred F344 rats developed moderately‐ to well‐differentiated primary oral squamous cell carcinomas (SCC) after treatment with the carcinogen 4‐nitroquinoline N‐oxide (4‐NQO) in vivo for 5–6 months. The inflammatory cell infiltrate associated with the primary tumours was predominantly of the macrophage lineage (CD45+, Ia+) and contained smaller numbers of CD8+ cells (NK cells, cytotoxic/suppressor T cells), CD5+ cells (T cells) and CD25+ cells (activated cells; T and NK cells). Keratinocyte cell lines were established from three lingual and one palatal SCC. By contrast to normal keratinocytes, tumour‐derived cell lines were immortal and independent of 3T3 fibroblast support. All of the tumour‐derived cell lines were tumorigenic in athymic (nu/nu) mice and showed contrasting latent periods of tumour development and histological differentiation; normal keratinocyte grafts were non‐tumorigenic in athymic mice. Three of four malignant cell lines formed well‐differentiated tumours in syngeneic F344 rats; the tumours regressed after 10–14 days. Regressing grafts contained significantly larger numbers of NK cells (CD5‐, CD8+) in the inflammatory cell infiltrate compared with that associated with primary tumours (p<0.04). One malignant cell line and normal keratinocytes were non‐tumorigenic in syngeneic hosts. The results demonstrate phenotypic variation in the cell‐mediated immune responses associated with the actively growing primary SCC and the regressing tumours in syngeneic hosts and suggest that NK cells, possibly activated by local T cell responses, are important for tumour rejection in this model.
Biotypes of oral Candida albicans isolates in human immunodeficiency virus‐infected patients from diverse geographic locations
Authors: Tsang P. C. S. , Samaranayake L. P. , Philipsen H. P. , McCullough M. , Reichart P. A. , Schmidt‐Westhausen A. , Scully C. , Porter S. R.
Published: April 2006

Oral Candida albicans isolates from HIV‐infected individuals in Hong Kong, Australia, Germany and England were characterised using a biotyping system based on enzyme profiles, carbohydrate assimilation patterns and boric acid resistance of the yeasts. A total of 44 biotypes were found amongst the 117 oral C. albicans isolates examined. The major biotype AIR accounted for 17.9% of all isolates while the second commonest biotype was A1S (11.1% of isolates). Whereas these two biotypes were isolated from all the regions studied, there were a number of other biotypes unique to individual countries. The data indicate that there are many different sub‐strains of oral C. albicans in HIV‐infected patients, some of which are globally prevalent. However, further work is required to ascertain the diversity of oral C. albicans biotypes, if any, in health and disease.
An association between recurrent oro‐genital ulceration and non‐steroidal anti‐inflammatory drugs
Authors: Healy C. M. , Thornhilll M. H.
Published: April 2006

Recurrent oro‐genital ulceration is a common condition of unknown aetiology. This paper describes a patient who had severe recurrent oro‐genital ulceration which was unresponsive to conventional therapy. The patient was taking non‐steroidal anti‐inflammatory drugs (NSAIDs) prescribed for osteoarthritis. When she stopped this medication, she had no further genital ulceration and the pattern of her oral ulceration was dramatically improved. There have been no previously reported cases of recurrent oro‐genital ulceration associated with NSAIDs.
The use of thrombomodulin to study epithelial cell differentiation in neoplastic and non‐neoplastic oral lesions
Authors: Tabata Masashi , Yonezawa Suguru , Sugihara Kazumasa , Yamashita Sukehide , Maruyama Ikuro
Published: April 2006

Thrombomodulin (TM) is a glycoprotein originally isolated from rabbit lung vasculature and characterized as a natural endothelial anticoagulant. Thrombin binds to TM noncovalently with high affinity. Thrombin ‐ TM complexes can activate protein C efficiently. Activated protein C inactivates factors Va and VIIIa and regulates the blood coagulation cascade. Thus TM converts thrombin from a procoagulant protease to an anticoagulant. TM is found on endothelial cells in veins, arteries and capillaries. Our previous study has shown that TM is also expressed on the cell surface of squamous epithelium. In the present study, we aimed to disclose differences in TM expression among normal, dysplastic, and malignant squamous epithelium in human oral mucosa by counting TM‐positive cells in each lesion. TM was uniformly expressed in the spinous layer of normal human oral squamous epithelium. The number of TM‐positive cells was not significantly different between normal epithelium, lichen planus and mild dysplasia. In contrast, in moderate and severe dysplasia and well‐differentiated squamous cell carcinoma (SCC), there were significantly fewer positive cells compared with normal epithelium. In SCCs, the periphery and the central keratinized area of tumor islands were often negative. The proportion of TM‐positive cells in poorly differentiated SCC was significantly lower than in well‐differentiated SCC. These results indicate that TM may have diagnostic value in the histological examination of oral premalignant and malignant lesions.
Betel quid chewing, cigarette smoking and alcohol consumption related to oral cancer in Taiwan
Authors: Ko Ying‐Chin , Huang Yung‐Li , Lee Chien‐Hung , Chen Mei‐Ju , Lin Li‐Min , Tsai Chih‐Cheng
Published: April 2006

A hospital‐based case‐control study of matched pairs was conducted to explore (a) the relationship between the use of betel quid chewing, cigarette smoking, alcohol drinking and oral cancer and (b) synergism between these factors. The case group consisted of 104 male and 3 female oral cancer patients and these were compared with 194 male and 6 female matched controls. We found by univariate analysis that alcohol consumption, smoking, betel quid chewing, educational level and occupation were associated with oral cancer. The adjusted odds ratios were to be found elevated in patients who were smoking and betel quid chewing. After adjusting for education and occupation covariates, the incidence of oral cancer was computed to be 123‐fold higher in patients who smoked, drank alcohol and chewed betel quid than in obstainers. The synergistic effects of alcohol, tobacco smoke and betel quid in oral cancer were clearly demonstrated, but there was a statistically significant association between oral cancer and betel quid chewing alone. Swallowing betel quid juice (saliva extract of betel quid produced by chewing) or including unripened betel fruit in the quid both seemed to enhance the risks of contracting oral cancer.
Oral signs and symptoms in patients with undiagnosed vitamin B12 deficiency
Authors: Field E. Anne , Speechley Janet A. , Rugman F. R. , Varga E. , Tyldesley W. R.
Published: April 2006

The oral manifestations of glossitis, stomatitis and mucosal ulceration in vitamin B12 deficiency have long been recognised. These oral changes may occur in the absence of symptomatic anaemia or of macrocytosis. The aim of this paper is to describe a retrospective study of the wide range of oral signs and symptoms reported by 14 patients found to have a previously undiagnosed vitamin B12 deficiency. None of the patients described in this study had generalised symptoms sufficiently advanced to arouse suspicions of vitamin B12 deficiency. The essential criteria for the diagnosis of pernicious anaemia are also discussed.
Murine autoimmune exocrinopathy: the minor salivary gland network shows a dichotomous pattern of histopathologic involvement
Authors: Barbeau Jean , Deslauriers Nöella
Published: April 2006

The minor salivary gland network of the MRL/1 mouse was investigated in a kinetic study and compared with the major submandibular gland. We report that minor salivary glands adopt two mutually exclusive patterns of inflammatory lesions depending on the gland. The first pattern is characteristic of human Sjogren's syndrome. It developed during the second month, affected 89% of the animals over 20 weeks old, and consisted of an accumulation of mononuclear cells around the duct system. Only the anterior buccal gland (ABG) showed this pattern, which is shared by the major salivary glands. The ratio of CD44+ to CD8+ cells was the same in lesions and in healthy tissue. No neutrophils were found in these lesions. The second pattern affected all the minor salivary glands except the ABG. These lesions were never observed before the age of 20 weeks and affected 38% of MRL/1 mice between the ages of 10–32 weeks. In this pattern, neutrophils were frequently found, but mainly gathered at the periphery of the gland lobules. That a systemic immunoregulatory defect may be expressed as two different patterns of histopathology in the minor salivary glands suggest that the network behaves as a dichotomous entity depending on particular microenvironmental influences.
Lack of correlation between DNA ploidy, Langerhans cell population and grading in oral squamous cell carcinoma
Authors: van Heerden W. F. P. , Raubenheimer E. J. , van Rensburg E. J. , le Roux R.
Published: April 2006

This study was undertaken to determine the inter‐observer reproducibility of the invasive cell grading method on oral squamous cell carcinomas and to correlate this with the DNA ploidy status and Langerhans cell (LC) population. Fifty formalin‐fixed paraffin‐embedded blocks that contained both tumor and adjacent normal epithelium were randomly selected. DNA ploidy analysis was performed on a flow cytometer and the LC population was determined using an immunohistochemical technique with anti‐S100 and anti‐HLADR primary antibodies. The inter‐observer correlation of the total malignancy score and individual morphologic features was highly significant. Thirty‐two of the 50 tumors were graded as poorly differentiated and 18/50 as moderately differentiated. Thirteen of 25 poorly differentiated tumors had an aneuploid DNA content compared with 9/18 of the moderately differentiated group. No statistical differences in the LC counts between the poorly and moderately differentiated and aneuploid and diploid carcinomas were found. This study showed that the invasive cell grading method is reproducible but no correlation was found between the grading results and the ploidy status or LC count.
Phenotypic differences in growth, matrix synthesis and response to nifedipine between fibroblasts derived from clinically healthy and overgrown gingival tissue
Authors: McKevitt K. M. B. , Irwin C. R.
Published: April 2006

Gingival overgrowth is a disfiguring condition affecting 10–20% of patients on nifedipine therapy. The pathogenesis of this condition, although unclear, is thought to involve an interaction between the drug and resident gingival fibroblasts. The aim of the present study was to investigate the cellular mechanisms underlying this condition using cell culture techniques. Gingival fibroblast cell lines were derived by explant culture from two patients on long‐term nifedipine therapy exhibiting gingival overgrowth (‘responders’) and from two patients on similar therapy with clinically healthy gingiva (‘non responders’). Comparative studies showed phenotypic differences between the two cell types, ‘responded cells having an increased growth potential and producing increased levels of protein and collagen compared to ‘non responded lines. Addition of exogenous nifedipine (10–1000 ng/ml) to cultures had no effect on ‘non‐responder’ cells but induced a significant inhibitory response in the ‘responder’ cells. Although adding support to the concept that nifedipine‐sensitive fibroblasts reside within overgrown connective tissue, the inhibitory effect of the drug on cell growth and matrix synthesis was surprising in view of the clinical appearance of this condition.
Heterogeneity of fibroblasts derived from human free and attached gingiva. Glycosaminoglycan synthesis and effects of phenytoin (PHT) treatment
Authors: Pagliarini A. , Stabellini G. , Carinci F. , Calura G. , Tognon M. , Evangelisti R.
Published: April 2006

Two fibroblast populations derived from free and attached gingiva (FGF, AGF) have been compared in cell culture. They exhibited the same morphology and similar cytoskeletal staining patterns, but were different in glycosaminoglycan (GAG) synthesis. FGF released larger quantities of GAGs than AGF in the medium. The extracellular accumulation of hyaluronic acid was higher in FGF than in AGF, whilst the reverse pattern was observed intracellularly. In the case of sulphated GAGs the extracellular concentration, compared to HA, was higher in AGF, while the intracellular concentration was higher in FGF. The two cell populations responded differently to phenytoin (PHT) administration. PHT treatment increased the proportion of intracellular sulphated GAGs in AGF and of extracellular sulphated GAGs in FGF.
Identification and characterization of gelatinases/type IV collagenases in jaw cysts
Authors: Teronen Olli , Salo Tuula , Konttinen Yrjö T , Rifkin Barry , Vernillo Anthony , Ramamurthy Nungavaram S , Kjeldsen Lars , Borregaard Niels , Hietanen Jarkko , Sorsa Timo
Published: April 2006

The molecular mechanisms of jaw cyst expansion probably involve interactions of matrix metalloproteinases (MMPs) and the tissue inhibitors of MMPs (TIMPs). In this study, molecular species of gelatinases present in neutral salt extracts of cyst walls and cyst fluids were characterized by functional activity measurements (type I gelatin and α‐casein zymography) and immunologically (Western‐blotting). The effects of various protein thiol‐group or cysteine‐switch reactants involved in the activation of collagenases were studied on cyst gelatinases and a gelatinases purified from human gingival fibroblasts (72 kD MMP‐2), gingival keratinocytes (92 kD MMP‐9) and polymorphonuclear neutrophilic leukocytes (92 kD MMP‐9). Western‐blottings revealed the presence of both 92 kD (MMP‐9) and 72 kD (MMP‐2) gelatinases in cyst wall extracts and cyst fluids. Western‐blot studies further suggested that jaw cyst gelatinases were only in part complexed with and thus inhibited by TIMP‐1 or TIMP‐2, suggesting that both MMP‐9 and MMP‐2 may participate in cyst expansion. MMP‐2 was also partially fragmented to a 68 kD form and additional lower molecular weight proteinases (<60 kD) were detected by α‐casein zymography and by Western‐blotting, suggesting proteolytic fragmentation. MMP‐9 was at least partially activated by all protein‐thiol group reactants and rather resistant to oxidative inhibition by hypochlorite (NaOCl); in contrast, MMP‐2 was activated by APMA but not at all by gold thioglucose (GTG) and was clearly inactivated by hypochlorite (NaOCl). This indicates MMP‐specific sensitivity to oxidative agents, but more specifically to preferential oxidative activation of PMN 92 kD MMP‐9 and oxidative inactivation of the fibroblast‐type 72 kD MMP‐2.
Oral manifestations of alpha‐mannosidosis: report of a case with ultrastructural findings
Authors: Ishigami Tetsuro , Schmidt‐Westhausen Andrea , Philipsen Hans Peter , Baiborodin Sergei I. , Gelderblom Hans , Reichart Peter A.
Published: April 2006

Alpha‐mannosidosis is a rare storage disease with distinct biochemical, clinical, histological and ultrastructural features. The oro‐facial findings in a 26‐year‐old man are described. Gingival and oral mucosal hyperplasias were studied using histology and transmission electron microscopy (TEM). The TEM findings were comparable to those of other tissues examined in previous reports, consisting of histiocytic cells containing storage vacuoles with fine reticule‐granular material.
Gingival biopsy in the diagnosis of giant axonal neuropathy
Authors: Bonnaure‐Mallet M. , Tricot‐Doleux S. , Le Berre C.
Published: April 2006

We report the case of a 4‐year‐old child presenting with a diagnosis of giant axonal neuropathy. This rare condition was diagnosed when the child was 15 months old and was confirmed using a gingival sample removed during a dental examination. Structural and ultrastructural analyses demonstrated the presence of numerous unmyelinated fibres with distended axons and the accumulation of intermediate filaments in Schwann cells, in fibroblasts and in endothelial cells. Cytological examination of connective tissue revealed the presence of mitochondria‐like particles. Scanning electron microscopic examination of hair revealed the presence of a longitudinal groove along the shaft. These characteristic features of giant axonal neuropathy demonstrate that gingival tissue can be used as an aid in its diagnosis.
Desmoplastic fibroma of the mandible associated with tuberous sclerosis
Authors: Miyamoto Youji , Satomura Kazuhito , Rikimaru Koichi , Hayashi Yoshio
Published: April 2006

A desmoplastic fibroma of the mandible in a 29‐year‐old Japanese woman with tuberous sclerosis is reported.
Distribution of p21ras during primary palate formation of non‐cleft and cleft strains of mice
Authors: Wang K. Y. , Chen K. C. , Chiang C. P. , Kuo M. Y. P.
Published: April 2006

Cleft lip, with or without cleft palate, is one of the most common defects in craniofacial formation. The primary palatogenesis of mice is similar to that of humans and spontaneous cleft lip is associated with genotype in both mice and humans. To investigate the temporal and spatial expression of ras genes in cleft (A/WySn) and non‐cleft strains of mice (BALB/cBy), a broad spectrum ras antibody was used. Positive staining was found in ectodermal, mesenchymal, and neuroepithelial cells of facial prominences before the primary palate formation stage (10 d 20 hr) in both strains. During the primary palate formation stage (11 d 20 hr), positive staining was found in the ectodermal and mesenchymal cells of the facial prominences of the non‐cleft strain but not in those of the cleft strain. These results suggest ras genes may play a role in the primary palatogenesis of mice. Cleft lip could be associated with the deficiency of ras gene expression during primary palate formation of mice.
Ultrastructural finding of vascular degeneration in fibrodysplasia ossificans progressiva (FOP)
Authors: El‐Labban N. G. , Hopper C. , Barber P.
Published: April 2006

The masseter and temporalis muscles were investigated ultrastructurally in 2 patients having fibrodysplasia ossificans progressiva (FOP). Results showed atrophy and necrosis of muscle fibres. Both cases contained cartilage which was calcified in the second case and was associated with degenerating chondrocytes. The blood vessels showed various changes, with haematoma formation and large fibrin deposits. Some of the fibrin deposits seen in the second case were surrounded with cartilage. This suggests that the cartilage probably forms as a reaction to an old haemorrhage. It is possible that the effect of the mutant gene found in FOP is on blood vessels rather than the normal regulatory mechanisms of the inducible osteogenic precursor cells. These degenerating blood vessels often result in haemorrhage and fibrin deposits; the fibrosis, cartilage or bone formation are probably secondary changes. Amianthoid fibres found in the tendon of the temporalis muscles of the second case, together with the other changes of fibrosis and cartilage formation, account for the severe restricted mouth opening suffered by these patients.
Histochemical study of lectin binding in the human fetal minor salivary glands
Authors: Adi M. M. , Chisholm D. M. , Waterhouse J. P.
Published: April 2006

The emerging synthesis of glycoconjugates containing specific oligosaccharides in developing human fetal labial and lingual salivary glands has been investigated by lectin histochemistry. An avidin‐biotin technique was used to study the binding of lectins from Ulex europeus I (UEA‐I), Dolichos biflorus (DBA), Glycine maximus (SBA), Helix pomatia (HPA), Arachis hypogaea (PNA) and Triticum vulgare (WGA) to specific sugars on sections of tissue from labial glands, glands of Blandin and Nuhn, glands of von Ebner and the dorsoposterior lingual salivary glands. Incipient synthesis of glycoconjugates in early glands and their presence in the cells and ducts of the later glands was shown. The study also showed a time‐related increase in both staining intensity and binding sites of serous acinar cells from all glands and for all lectins used. For mucous cells, peak intensity of staining was reached by the middle phase of development. During later gland development this intensity was maintained in dorsoposterior lingual glands but tended to decline in labial glands. The various lectins showed different degrees of binding but UEA‐I lectin generally bound the L‐fucose sugar group in all salivary glands at all gestational ages. The results showed that lectins appear to bind to the oligosaccharides on epithelial cell surfaces of fetal salivary glands at all stages of development. The degree of change depends upon the stage of differentiation and maturation of the glands.
Oral manifestations in glycogen storage disease type 1b
Authors: Salapata Yolanda , Laskaris George , Drogari Evridiki , Harokopos Eustathios , Messaritakis John
Published: April 2006

Glycogen storage disease type 1b is a rare metabolic disorder which affects the transport system of glucose‐6‐phosphatase metabolism. As a result, hepatomegaly, failure to thrive, renal dysfunction and recurrent infections occur in affected patients. In this paper, the oral complications in three children with glycogen storage disease type 1b are discussed. Oral ulcers were a common rinding, probably due to severe neutropenia and impaired neutrophil migration which characterises the onset of this rare disorder.
Enamel microhardness and histological features of composite enamel pearls of different size
Authors: Gašperšič Dominik
Published: April 2006

The aim of this study was to investigate the enamel microhardness and the histological features of eight enamel pearls of various size. The microhardness of the pearl enamel ranged from 272.4 to 407.2 Vickers microhardness values (VMV) and resembled that of the enamel of the carrier teeth (277.1–424.3). A histological resemblance between the tissues of the enamel pearls and those of the carrier teeth was also found. The resemblance was more pronounced in larger pearls, which showed a variability of the enamel microhardness and structure in the occlusal‐cervical direction typical of the tooth crown. Large pearls also exhibited a root and a pulp. Some histological features of the enamel pearls were probably caused by pressures exerted on the developing pearl by its surroundings. It is suggested that the histogenesis of small and large pearls is based on the ability of the developing root of the carrier tooth to behave in part as a new tooth germ.
Altered expression of extracellular matrix proteins and integrins in oral lichen planus (OLP)
Authors: Becker J. , Schuppan D.
Published: April 2006

The immunohistochemical distribution of collagens type I, III, IV, V, VI, of undulin and tenascin. and of integrins α2, α3, α4, α5, α6 and β4, was studied in 14 biopsies of oral lichen planus (OLP), 5 biopsies of orthokeratinized gingiva and 4 biopsies of oral fibrous hyperplasia. The localization of extracellular matrix proteins showed altered expression in OLP when compared to normal oral mucosa, with two principal patterns corresponding to the reticular or atrophic type. Whereas in the reticular type a focal loss of immunoreactivity for collagen types I, III, V, VI and undulin was noted in areas with a cellular infiltrate, in the atrophic variant almost complete loss of immunoreactivity of the subepithelial extracellular matrix was found. There was no clear correlation between the distribution of extracellular matrix proteins and their integrin receptors. The present findings suggest that the autoimmune reaction in OLP might not be primarily targeted to oral keratinocytes but to an unknown antigen in the connective tissue stroma. The changes in the subepithelial extracellular matrix associated with the inflammatory reaction might, especially in the atrophic variant, impair the cross‐talk between epithelium and mesenchyme and favour both the loss of barrier function and the development of erosions in the clinical course of the disease.
Epithelial cell kinetics in oral leukoplakia
Authors: Warnakuiasuriya K.A.A.S. , MacDonald D.G.
Published: April 2006

Cell proliferation in oral leukoplakia has been studied by estimating the number of cells in the S phase using in vitro3H thymidine labelling. The labelling index was found to be increased 1.77 fold in leukoplakias compared to the clinically normal control sites (P < 0.005). This rise in labelling index was found to be related to an increase in the proportion of the cells in the basal cell layer engaged in cell production. Both leukoplakia and the control specimens showed epithelial atypia, although in the latter samples this was mild yet suggestive of a possible field change in the oral epithelium of a small group of tobacco users. A significant positive correlation was found between the epithelial atypia score and the labelling index. This raises the possibility of using the labelling index as an objective prognostic marker in assessing potential malignancy in oral leukoplakia lesions.
Liposarcomas of the oral tissues: a clinicopathologic study of four tumors
Authors: Minić A. J.
Published: April 2006

Liposarcomas of the oral tissues are rare. There have been 28 previously reported in the literature. A clinicopathologic study of 4 patients with liposarcoma involving the oral tissues is presented ‐ one in the tongue, one in the palate, and two in the submandibular space. Two of the tumors were myxoid, one was of well‐differentiated type and one was of pleomorphic type. Three of the lesions were diagnosed clinically as benign. The most important lesson to be learned from the histopathology is the positive identification of atypical lipoblasts. Follow‐up data indicate that prognosis generally corresponds to the tumor type. The patients with myxoid and well‐differentiated liposarcoma remain alive and with no evidence of disease. The patient who died of tumor had a pleomorphic liposarcoma. Treatment of these lesions should consist of wide surgical excision and consideration of adjunctive or palliative radiotherapy.
Observer variability in the histologic assessment of oral premalignant lesions
Authors: Karabulut A. , Reibel J. , Therkildsen M. H. , Praetorius F. , Nielsen H. W. , Dabelsteen E.
Published: April 2006

Histopathologic examination of oral leukoplakias has a major impact on the assessment of prognosis and treatment planning. We investigated the extent of agreement in grading epithelial dysplasia between pathologists with the same or different educational backgrounds. Two general pathologists and two oral pathologists were each given 100 sections of oral leukoplakia to grade from no dysplasia to carcinoma in‐situ. The interobserver agreement rates were in the range of 49% to 69%. The calculated kappa values were in the range of 27% to 45%), showing poor to moderate agreement between the pathologists. When comparing the kappa values between the two pairs of pathologists with the same education, these values did not diverge from the general level of kappa values, indicating that the interobserver variability was due to individual differences rather than to educational background.
Anti‐salivary antibodies in primary Sjögren's syndrome
Authors: Atkinson Jane C. , Royce Leah S. , Wellner Robert , Pillemer Stanley R. , Bermudez Deborah , Fox Philip C.
Published: April 2006

Earlier studies have described an antibody that recognized salivary ductal epithelium in sera from 15–50% of patients with primary Sjögren's syndrome; however, the specific salivary antigen in those studies was not identified. The present study further investigated this unknown salivary antigen. Twenty‐nine of 31 patients (94%) with primary Sjögren's syndrome demonstrated IgG antinuclear antibodies that bound to an epithelial cell line with ductal characteristics derived from a human salivary gland. Seventy‐seven percent of these patients had serum antibodies that bound to ductal cells of normal human parotid tissue after formalin fixation. Western blots of cell extracts, immunofluorescence, and adsorption studies indicated that SS‐A/Ro and SS‐B/La were the antigens recognized in the salivary cell line. The pattern of fluorescence seen when anti‐SS‐B/La bound to normal parotid tissue was identical to the fluorescence pattern of the anti‐salivary ductal antibodies described in earlier literature.