[Significance of epithelial-mesenchyme interactions in microvascular pedicled small intestine transplants replacing oral mucosa].
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Biomedical subjects
Publications and source records attributed to P Reichart.
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The aim of the present investigation was to study whether a technique based on the principle of guided tissue regeneration is able to generate new osseous tissue around osseointegrated implants in humans. 14 titanium implants (IMZ) were inserted in 4 patients. The fixtures were modified by hydroxyapatite (HA) or titanium discs measuring 3 mm in height, which were screwed onto the implants. The modified implants were inserted in such way, that the discs were above the level of the alveolar bone. 3 modalities of treatment were performed. In group I HA granules were placed on the bone around the disc-implant-constructions and completely covered by an ePTFE membrane in order to create a space for ingrowth of bone-derived cells. In group II the membrane alone was placed and in the control group HA granules alone were used. After complete closure of the flap and 2-4 months of healing, the membranes including the generated tissue and the discs were removed and processed for histological examination. Clinical results demonstrated that in group I hard tissue had formed underneath the membrane, which strongly adhered to alveolar bone. Histological examination revealed new formation of trabecular bone. When the membrane alone was used, the created space was almost completely reduced during healing and no significant tissue formation had occurred. The greatest clinical problem was flap dehiscence over the membrane. In the control group the HA granules and discs were encapsulated in connective tissue. Limited by the small number of sites, the study indicates that a membrane technique according to the principle of guided tissue regeneration promotes new bone formation around osseointegrated implants in humans.
A case with oral Kaposi's sarcoma (KS) is reported that regressed during therapy with Zidovudine (AZT) which was started 5 months after the first dermal and oral tumours were noted. After 6 months of treatment the absolute number of T-helper cells had increased from 54/microliters to 232/microliters and the ratio of T-helper to T-suppressor cells from 0.15 to 0.3. During the same time the lesions of KS on the gingiva, uvula and the body as well as the face disappeared. The lesion of KS on the hard palate regressed.
Twelve biopsies of clinically normal oral mucosa taken from HIV seropositive patients have been investigated by means of light- and electron microscopy. Vascular abnormalities were found in all biopsies, regardless of the clinical stage of the HIV infection. In particular slit-like vascular channels, sparseness of intercellular junctions and swollen, protruded endothelial cells with an increased quantity of Weibel-Palade bodies were noticed. These findings were similar to those described in lesions of early stage Kaposi's sarcoma.
Oral hyperpigmentation has been observed in six HIV-infected patients, in two of whom systemic medication (ketokonazole, clofazimine) was supposed to be etiologically involved. Histologically, pigment was found in epithelial basal cells and particularly in subepithelial connective tissue. Ultrastructurally, the presence of premature melanosomes in subepithelial keratinocytes was of interest. Stimulation of melanocytes during HIV infection may occur in association with immunopathologic changes in the oral mucosa.
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Seventeen biopsies taken from oral mucosa of HIV infected patients were analysed for the distribution of CD4+/CD8+ T-lymphocytes and Langerhans cells. The results were evaluated statistically. An increase in the absolute number of CD4+ and CD8+ cells in HIV infected patients without clinical symptoms, ARC or AIDS was seen in the connective tissue stroma when compared with normal oral mucosa from sero-negative patients. However, the ratio between CD4+/CD8+ cells was decreased due to the disproportionate increase of CD8+ cells. These findings did not show statistical correlation with the clinical status of the infection. In contrast to the increase in absolute number of CD4+/CD8+ cells the number of Langerhans cells was unchanged when compared with the control group. Using four different monoclonal antibodies against virus structural proteins (2 X anti p24, gp41, gp120) two of 26 patients showed labelled cells in consecutive sections in the same connective tissue areas. It was assumed that latently infected mononuclear cells invaded the oral mucosa together with uninfected cells of the cellular immune system.
Three cases of HL from the lateral border of the tongue of male homosexual AIDS patients were investigated by thin section electron microscopy. Keratinocytes contained condensed chromatin in their pyknotic nuclei and a few organelles in the oedematous cytoplasm. Chromatin was in close association to the nuclear membrane and showed a punched-out appearance. Particles typical of the herpes virus group were abundant in the upper two thirds of the epithelium in all three cases. Virus particles were seen frequently in the nuclei of the ballooned keratinocytes, but rarely in cells containing Candida albicans. Viral nucleocapsids were observed budding at the inner nuclear membrane, thereby acquiring the prospective viral envelope. Complete, enveloped virions were found in the endoplasmic reticulum and in the extracellular space. These virions were identified immunohistochemically as Epstein-Barr virus (EBV) using two monoclonal antibodies directed against EBV capsid and membrane antigen, respectively. Candida albicans was observed in the stratum corneum and in the upper layer of the stratum spinosum. Special cytoplasmic tubular structures arranged in parallel bundles were found in koilocytotic cells in addition to characteristic membrane structures composed of undulating convoluted membranes. Epithelial basement membranes were always intact.
2 cases of disorders of craniofacial nerves resulting from progressive multifocal leucoencephalopathy are described. Clinical symptoms occurred as facial paralysis, hypaesthesia, hemianopsia and deafness. In both patients, the impairment of the central nervous system (CNS) preceded indicative AIDS symptoms. Both patients died about 3 months after the first CNS symptoms had been diagnosed. Clinical and neurohistopathological findings as well as differential diagnoses are discussed.
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Thirty biopsies of oral mucosal lesions and normal oral mucosa were obtained from 26 HIV-seropositive individuals and studied for virus infections with Epstein-Barr virus-specific DNA probes (EBV). In situ DNA hybridization was carried out on frozen and formalin-fixed, paraffin-embedded tissues. Specifically bound biotinylated virus probes were detected with the streptavidin-gold-silver technique and visualized by standard and interference reflection microscopy. In 9/30 biopsies, EBV DNA was clearly demonstrated in the upper two thirds of oral epithelia. This finding corresponded to peculiar cytopathic effects including ground glass nuclei, basophilic nuclear inclusions, and ballooning of the cytoplasm, which were concentrated in the upper two or three layers of the stratum spinosum. Cytopathic effects together with the demonstration of EBV DNA were demonstrated in seven cases of tongue mucosa, and two cases derived from the gingiva. When comparing clinical and pathological findings with DNA detection rates, we saw 5/9 hairy leukoplakias associated with EBV infections. Four positive cases (two samples from the tongue, two gingival specimens) had not been regarded as hairy leukoplakia clinically. EBV infection of the oral epithelium occurred in male homosexuals (7 cases) and in male/female intravenous drug abusers (2 cases). Among the nine EBV-positive cases, 2 patients were asymptomatic, 4 patients were grouped into the ARC-, and 3 individuals into the AIDS-category. We conclude that HIV-seropositive patients are particularly prone to develop productive EBV infections in oral epithelia. This infection most frequently appears at the lateral border of the tongue, but may also occur at other sites of the oral cavity, and may already exist in a preclinical stage prior to the development of oral white lesions (hairy leukoplakia).
Twelve oral AIDS-associated Kaposi sarcomas (KS) were studied for the distribution of extracellular matrix components using indirect immunofluorescence. Staining for basement membrane (BM) components revealed two distinct patterns of distribution: a delicate and partly fragmented lining of BMs around sinusoid-like vascular spaces or an occasional diffuse interstitial fluorescence in the tumour stroma; or an irregular broad rim of fluorescence in walls of larger blood vessels. These findings support a vascular cell origin of the endothelial- and spindle cell component in KS. The tumour stroma was almost completely negative for collagen type V and undulin, whereas an intensive fluorescence was noted for procollagens type I, III and collagen type VI. In areas adjacent to KS a loss of procollagens type I and III, collagens type V, VI and undulin was noted. An intimal sheath of collagen type V was usually absent from blood vessels of the tumour or the peritumourous connective tissue. Immunohistochemical findings indicate that the preexisting interstitial connective tissue matrix is destroyed during tumour invasion and that subsequently procollagens type I, III and collagen type VI are synthesized de novo by cells of the tumour stroma.
In order to evaluate the effect of concurrent administration of areca nut and sodium nitrite, a long-term feeding study was conducted with 120 Syrian hamsters. The animals were divided into four treatment groups, each consisting of 15 males and 15 females, and received 2 g/kg diet of sodium nitrite (group I), 20 g/kg diet of powdered areca nut (group II), 2 g/kg diet of sodium nitrite plus 20 g/kg diet of areca nut (group III) or powdered diet only (group IV) throughout their lifetime. Urine samples from all groups were analysed for N-nitrosonipecotic acid (NNIP), a major urinary metabolite of areca-nut-derived nitrosamines. NNIP was only detected in the urine of hamsters fed nitrite plus areca nut (concentration: 1.9 +/- 0.9 ng/ml urine), indicating that areca nut alkaloids underwent in vivo nitrosation to form areca-nut-specific nitrosamines. The total tumour response was not significantly elevated in groups II and III. Hamsters of group III had a markedly, but also insignificantly higher frequency of malignant tumours than those of the other groups, with a statistically significant increase in malignant lymphomas in the males. Although limited by the low number of animals per group, these results indicate that exposure to nitrite together with areca nut constituents appears to enhance the risk of developing malignancies.
A series of 22 squamous cell carcinomas (4 cases grade 1; 11 cases grade 2; 7 cases grade 3) of the oral cavity (13 cases), (naso-)pharynx (5 cases) and larynx (4 cases) were studied by conventional light microscopy and filter (dot blot) hybridization for the detection of human papillomavirus (HPV) DNA. In 4 carcinomas, tumour-free tissue from the resection margins of the surgical sample was examined in addition to the tumour specimen. The same kind of investigation was carried out on 4 oral leukoplakias without dysplasia. All cases were thoroughly examined for HPV-associated cytopathic effects (koilocytosis). In all cases, material was obtained for DNA extraction followed by dot blot hybridization. DNA hybridization was carried out under stringent conditions with mixed probes of HPV 6/11 as well as HPV 16/18. Koilocytosis was observed in 10/22 carcinomas (45%, 4/4 G1 tumours, 6/11 G2 tumours, none out of 7 G3 tumours) and 3/4 leukoplakias. Koilocytosis always occurred at the tumour surface or the surface epithelium immediately adjacent to the tumour. HPV DNA was found in 8/22 carcinomas (36%, 2/4 G1 tumours, 5/11 G2 tumours, 1/7 G3 tumours). We observed HPV 16/18 infections in 3 cases and HPV 6/11 infection in 1 case. The other 4 cases were positive under relaxed conditions and, thus, could not be grouped into one of the examined types of HPV infections. In 4 carcinoma cases, tumour tissues and resection margins were examined. 3/4 cases showed concordant findings, i.e. in 2 cases tumour tissue and tumour-free mucosa (1-2 cm distant to the tumour) were positive for HPV, 1 case was negative in both samples. In 6/8 cases positive for HPV, HPV DNA detection corresponded to the observation of intensive koilocytosis. The leukoplakias were seen to harbour HPV DNA in 3 cases (1 case: HPV 6/11; 1 case: HPV 16/18; 1 case: positive under relaxed conditions). We did not observe HPV DNA in normal mucosal tissues. Our findings provide further evidence for the presence of HPV infections in tumours of the upper respiratory and digestive tract. Prospective studies now have to clarify the biological importance of HPV infections in this group of human cancer.
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