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Biomedical subjects

P Holmstrup

Publications and source records attributed to P Holmstrup.

At least 73 records · Page 4Linked to original sources

Surgical treatment of premalignant lesions of the oral mucosa.

Oral premalignant lesions were treated by surgical excision in 61 patients. Criteria for inclusion in the study were epithelial dysplasia varying from slight to carcinoma in situ, or a non-dysplastic lesion located sublingually or on the tongue. The clinical diagnosis of the treated lesions were: erythroplakia 10, erythroleukoplakia 15, nodular leukoplakia 9, verrucous leukoplakia 9, homogeneous leukoplakia 13, and lichen planus 5. The surgically created defects were closed by direct approximation of the wound edges in 25 patients, transposition by a local mucosal flap in 9, covered with a free mucosal graft in 3, and by a free split skin transplant in 24 patients. The patients have been followed for an average period of 3.9 years after the operation. A recurrence rate of 20% was found, and 3 carcinomas developed in the follow-up period. The importance of using a surgical technique permitting histological examination of the entire lesion was documented by the finding of 4 superficial carcinomas in the excision specimen, undiagnosed in the preoperative biopsy.

Adult↗

Possible mycological etiology of oral mucosal cancer: catalytic potential of infecting Candida albicans and other yeasts in production of N-nitrosobenzylmethylamine.

Yeasts were isolated from 12 cases of oral precancerous lesions (leukoplakia and erythroleukoplakia) by sampling the lesion as well as normal mucosa of each patient, yielding 21 strains of Candida albicans belonging to 15 biotypes, two strains of C. tropicalis, one strain of C. parapsilosis and two strains of Torulopsis glabrata. Biopsies were obtained from the lesions for histologic examination. The catalytic potential of the yeast strains to form N-nitrosobenzylmethylamine (NBMA) from the precursors N-benzylmethylamine and nitrite was assessed at pH 6.8. The NBMA produced was identified and quantitated by h.p.l.c. and confirmed by g.c.-m.s. Nitrosation rates were calculated as total nitrosamine subtracted the chemically produced nitrosamine, and related to number of yeast cells. The yeast strains differed in nitrosation potential (P less than 0.001), ranking from 0 to 1.2 micrograms NBMA/10(6) cells. Candida albicans strains, belonging to the biotypes 051, 147, 151, 153, 157 and 353, which constitute more rarely occurring biotypes, exhibited the highest nitrosation potential. Candida tropicalis, C. parapsilosis and T. glabrata were ranked lower. Strains with high nitrosation potential were generally isolated from lesions with more advanced precancerous changes. The yeast cells were present in the superficial part of the epithelium of the lesions as branching mycelium, and in some cases extending from the mucosal surface to the deeper epithelial cell layers. This might represent a fungal transportation system which could channel precursors in the saliva at the mucosal surface to the deeper part of the epithelium where the produced nitrosamine could be deposited. Thus, further evidence is provided supporting the hypothesis that certain strains of C. albicans and of other yeasts play a causal role in the development of oral cancer, by means of endogenous nitrosamine production.

Candida↗

Degradation of IgA1, IgA2, and S-IgA by Candida and Torulopsis species.

Nine strains, isolated from leukoplakias or normal mucosa of the oral cavity, and representing the species Candida albicans, C.tropicalis, and Torulopsis glabrata were tested for the capacity to degrade IgA1, IgA2, and S-IgA in liquid cultures. IgA fragments were characterized by SDS-PAGE of culture supernatants in combination with immunoblotting analysis using antibodies specific for heavy chain and light chain determinants. Strains of C.albicans and C.tropicalis were found to express stronger proteolytic activity than a strain of T.glabrata. The three types of IgA were all degraded, alpha-chains being the primary targets. Immunoblotting analysis indicated that divalent fragments corresponding to the deletion of one or both of the Fc alpha constant domains (F(abc)2 alpha or F(ab)2 alpha) were produced. Monovalent half-molecules corresponding to these fragments could also be detected, suggesting that the yeast strains were capable of cleaving inter-alpha-chain disulphide bridges. The possible consequences of yeast-induced degradation for the function of IgA antibodies are discussed.

Biotransformation↗

Yeast organisms associated with human oral leukoplakia.

Oral leukoplakia is a lesion of variable clinical behaviour and a malignant transformation rate of 3-6%. Leukoplakia exhibits various histologic features, hyperkeratinization being the most consistent. As yeast organisms have been encountered in a high proportion of leukoplakia cases, a causal role has been suggested for these organisms. Candida albicans is by far the most commonly isolated yeast from leukoplakia, but also other Candida species as well as Torulopsis and Saccharomyces species may be encountered. The species composition of the mycoflora in leukoplakia does however not differ from that of normal oral mucosa. Subspecies differentiation of C. albicans has revealed the existence of different oral strains between individuals and further, strain differences of C. albicans in leukoplakia and in normal mucosa have been observed. This procedure may lead to isolation and identification of the yeast organisms causally associated with leukoplakia.

Candida↗

[Barodontalgia].

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Adolescent↗

Subjectivity in evaluating oral epithelial dysplasia, carcinoma in situ and initial carcinoma.

During the 2nd Meeting of the International Association of Oral Pathologists in Amsterdam (1984), an exercise was held to study subjectivity in evaluating oral epithelial dysplasia. A poster with 9 color photomicrographs was presented to be evaluated anonymously by the participants. A total of 72 submitted diagnostic suggestions. In Table 1 these suggestions are given together with the diagnosis by the authors. A surprisingly wide spectrum of diagnostic suggestions was found indicating the need for an internationally accepted set of criteria for oral epithelial dysplasia.

Adolescent↗

Studies on the deposition of laminin and type IV collagen in human oral mucosa transplanted to nude mice.

Normal human oral mucosa (20 biopsies) and similar tissue transplanted to nude mice (44 transplants) were investigated for the presence of laminin and type IV collagen, using an indirect immunofluorescence staining technique. Laminin and type IV collagen were consistently found in the basement membrane area of the epithelial-stromal junction, and of the vessels of both normal oral mucosa and oral mucosal transplants. De novo synthesis of laminin and type IV collagen by transplanted epithelium was evidenced by the finding of an increased thickness of basement membrane deposits. New basement membrane-like material was also seen between the migrating human epithelial cells and the murine connective tissue. By application of species-specific monoclonal antibodies to human laminin and type IV collagen, it was demonstrated that human epithelial cells have the ability to participate in the information of their basement membranes. The use of both species-specific and species-unspecific antibodies showed that the vessel supply of the transplants was of both human and murine origin.

Adult↗

EDTA separation and recombination of epithelium and connective tissue of human oral mucosa. Studies of tissue transplants in nude mice.

A possible epithelial-mesenchymal interaction in determining epithelial histologic features of human oral mucosa was examined. The study comprised 74 biopsies of normal buccal mucosa and 54 biopsies of normal palatal mucosa. Epithelium was separated from connective tissue by the use of 1 mM ethylenediamine tetraacetate dihydrate. Self-recombined and cross-recombined epithelial and connective tissues and connective tissue sheets alone were transplanted to subcutaneous sites of nude mice. Histologic examination of cross-recombined palatal epithelium/buccal connective tissue transplants showed a change in keratinization pattern but no major change in number of epithelial cell layers as the result of connective tissue influence. Transplanted sheets of connective tissue after growth for 14 days showed that complete separation of biopsies from buccal mucosa had been obtained. However, palatal mucosa had been incompletely separated as evidenced by re-epithelialization of most of the connective tissue transplants. The consequences of the incomplete palatal epithelium-connective tissue separation are discussed.

Adolescent↗

Identification of human connective tissue in transplant of human oral mucosa in nude mice.

The present study describes a method for identification of connective tissue of human oral mucosal transplants in nude mice. The method was based on the development of a murine antiserum to human fibroblasts. After absorption with murine fibroblasts the antiserum in an immunofluorescence method appeared to react specifically with human connective tissue of frozen sections, whereas the antiserum did not react with murine connective tissue. The antiserum, applied to frozen sections of human oral mucosal transplants in nude mice, could distinguish between human and murine connective tissue in the sections. The ability to distinguish between the two types of tissue was utilized to elucidate a possible relation between epithelial morphology and underlying type of connective tissue. It was found that the formation of rete ridges of transplanted human oral epithelium was dependent on the presence of subepithelial human connective tissue. The method described may be useful for the recognition of human tissue in experimental studies of human transplants to other species.

Adolescent↗

The junction zone of human epithelium and foreign stroma. Ultrastructural observations in human oral mucosal transplants in nude mice.

This study describes ultrastructural features of epithelial-stromal junction of human buccal and palatal mucosal transplants and their outgrowths in nude mice. The investigation included transplant epithelium overlying human connective tissue in 27 cases, epithelial outgrowth formed over murine connective tissue in 33 cases, and over Millipore filter in 12 cases. The epithelial-stromal junction of the transplants differed from the normal state only in the presence of lamina densa loops projecting into the connective tissue and in lamina densa interruptions and duplications. In contrast the epithelial outgrowths demonstrated flattening of epithelial basal cells, lack of proximal epithelial cell projections, lack of complete hemidesmosome complexes, lack of distinct lamina densa, and lack of anchoring fibrils. It is suggested that these changes may be due to lack of necessary interaction between the human epithelium and the foreign stroma.

Adolescent↗

Bone resorption in cholesteatomas. An experimental study.

A model for studying different aspects of human cholesteatomas in vivo in the immunodeficient "nude' mice is described. Epithelial-mesenchymal interaction was studied in human cholesteatoma membranes, transplanted to the flank region. Findings of cystic lesions lined by stratified keratinizing epithelium were frequent and the connective tissue reaction were weak. Furthermore human cholesteatomy membranes were transplanted into the middle ear cavity of the "nude' mice. After 21-28 days bone resorption was shown in the labyrinthine capsule, not always with sign of inflammation.

Animals↗

Clinical, therapeutic, and pathogenic aspects of chronic oral multifocal candidiasis.

In 32 patients (11 females, 21 males) the diagnosis of chronic oral multifocal candidiasis was established on the basis of erythematous, plaquelike, or nodular lesions in two or more of the following locations: commissural area, palate, or dorsum of the tongue. Hyphae and/or pseudohyphae of Candida-like organisms were demonstrated in PAS-stained smears from all lesions. Ninety-seven separate lesions were registered. Thirty patients experienced pain, burning, or itching from affected areas. All of the patients were tobacco smokers, and 21 were denture wearers. The patients were treated with antimycotics; the median length of treatment was 46 days for denture wearers and 44 days for nondenture wearers. After antimycotic therapy the change in the lesions followed certain patterns which were determined by the original type of lesion. Palatal lesions in nondenture wearers and nodular lesions of the commissural areas showed the highest recurrence rate after 6 and 12 months. The pathogenic role of tobacco and other factors in the development of candidal infection are discussed.

Adult↗

Human odontogenic keratocyst transplants in nude mice.

Specimens from human odontogenic keratocysts were subcutaneously transplanted to nude mice. The transplants were harvested after 14-66 d with a rate of successful recovery of 87%. The histologic epithelial features in the original odontogenic keratocyst and their transplants were essentially similar. This included a well-defined basal cell layer composed of columnar and cuboidal cells, the number of cell layers and the keratinization pattern. Epithelial outgrowths from the transplants were found in 19 of 26 cases. The outgrowths over murine connective tissue in the majority of cases were keratinized, but the phenotypic expression differed with respect to the shape of basal cells and number of cell layers.

Animals↗