[Immunohistochemistry of adnexal tumors of the skin].
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Adenoma↗
Biomedical subjects
J Kanitakis
Publications and source records attributed to J Kanitakis.
Detection of human immunodeficiency virus-DNA and RNA in the skin of HIV-infected patients using the polymerase chain reaction.
The presence of HIV genomic-associated nucleic acids (DNA and RNA) within biopsies of normal-appearing skin and various skin lesions obtained from a group of 33 HIV-infected patients was investigated by using the polymerase chain reaction (PCR). In order to define the localization (dermal vs. epidermal) of HIV, the PCR was carried out separately on the dermis and the epidermis in 21 of the specimens. Altogether, HIV-DNA and HIV-RNA were detected, respectively, in 89% and 47% of the specimens included in this study; both DNA and RNA were detected more frequently in the dermis (90% and 43%, respectively) than in the epidermis (62% and 5%, respectively). No correlation could be established between the presence of HIV genomic material, the nature (normal-appearing vs. diseased) of the skin specimen studied, and the clinical or biologic severity of HIV infection, as evidenced by the CDC stage classification and the number of peripheral CD4+ cells. It seems, therefore, that the HIV is very frequently present within the skin during the course of HIV infection; however, its precise cellular localization and pathologic significance await further investigation.
Adult↗
Oral hairy leukoplakia in a HIV-negative renal graft recipient.
Oral hairy leukoplakia (OHL) is seen almost exclusively in patients infected with HIV. A case is reported of OHL occurring in a patient who was seronegative for HIV and who had a renal graft. This occurred following an increase in his treatment with immunosuppressive drugs.
Adult↗
Reactivity of HMB-45 monoclonal antibody with sweat-gland tumours of the skin.
HMB-45, a monoclonal antibody claimed to be specific for malignant melanoma, has been observed to react with normal eccrine sweat glands and occasionally with normal mammary and bronchial epithelium. In this study we show that HMB-45 also decorates cells in approximately 15% of various sweatgland tumours of the skin. This finding, along with the reported reactivity on mammary carcinomas further outlines the lack of absolute specificity of HMB-45 for cells of the melanocytic lineage.
Antibodies, Monoclonal↗
[Non-immunologic effects of cyclosporins].
Cyclosporins are a group of molecules produced by fungi. The main cyclosporin, cyclosporin A, is widely known for its immunologic properties which have made it the leading drug for prophylactic therapy of transplant rejection. However, cyclosporin A (as well as several of its analogs with or without immunosuppressive properties) has a broader and more varied spectrum of biologic effects both in vivo and in vitro; renal, pancreatic, endothelial, muscle and nerve cells, hepatocytes, keratinocytes, and some microorganisms (plasmodium, schistosoma) are target cells whose metabolism or growth is affected by cyclosporins. Some of these activities are responsible for adverse effects but others may warrant the use of selected cyclosporins in clinical situations other than organ transplants.
Animals↗
Cyclosporin A exerts a cytostatic effect in vivo on human and murine epithelial cells.
Cyclosporin A (CsA) is a potent immunosuppressant that may also affect nonlymphoid cells. Indeed, CsA exerts a growth inhibition in vitro of several human and animal, normal and neoplastic cell types. To assess a possible in vivo direct cytostatic activity of CsA, the authors evaluated the proportion of S-phase (5-bromo-2'-deoxyuridine incorporating) cells of epithelial origin (skin, tongue, esophagus) of congenitally athymic (nude) mice bearing xenografts of human skin and receiving a daily subcutaneous injection of 50 mg/kg of CsA for 3 weeks. As compared with control animals, CsA-treated mice showed a decreased labeling index (LI) of all the epithelial tissues studied, which was statistically significant in the case of epidermis (both human and murine) and the tongue. Because nude mice lack T-cell-mediated immunity, these results suggest that CsA also exerts an immunologically independent antiproliferative activity on epithelial cells in vivo and they also highlight the interest in pursuing studies on cyclosporins as cytostatic agents.
Animals↗
Cyclosporine. An immunosuppressant affecting epithelial cell proliferation.
Cyclosporine (cyclosporin A) is an immunosuppressant that selectively acts on the CD4+ subset of T lymphocytes. Recent results of experimental in vitro and in vivo studies, as well as evidence obtained through the clinical use of cyclosporine in humans, strongly suggest that cyclosporine may exert a direct effect on the growth of several epithelial cell types. Thus, cyclosporine, while stimulating the growth of hair follicle keratinocytes with a resulting hypertrichosis, appears to exert a cytostatic effect on several epithelial cell types of human and animal origin. This antiproliferative effect is shared by some minimally immunosuppressive or nonimmunosuppressive cyclosporine analogues, suggesting that the molecular mechanisms that modulate epithelial cell growth differ from those responsible for immunosuppression. This newly discovered pharmacologic property of cyclosporine may hopefully lead to the wider use of nonimmunosuppressive cyclosporines in the treatment of hyperproliferative epidermal diseases.
Animals↗
Repigmentation of human skin xenografted onto nude mice.
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Animals↗
Histological and ultrastructural effects of cyclosporin A on normal human skin xenografted on to nude mice.
Cyclosporin A (CsA) is a potent immunosuppressant with a selective activity on T-helper lymphocytes. However, CsA also exerts biological effects on non-lymphoid cells (fibroblasts, endothelial and epithelial cells). CsA can inhibit in vivo and in vitro DNA synthesis of epidermal keratinocytes (EK) and induces in vivo morphological alterations of kidney epithelial cells. In the present study we investigated the in vivo effects of a short-term CsA treatment (50 mg/kg per day) on DNA synthesis (evaluated through 5-bromo-2'-deoxyuridine incorporation) and on the histological features of normal human skin xenografted (NHSX) on to congenitally athymic nude mice. When compared with control NHSX, CsA induced a statistically significant inhibition of DNA synthesis of NHSX EK. At the light- and electron-microscopic level, apart from a decrease in the thickness of the viable epidermis of NHSX (statistically non-significant), no noticeable differences between treated and control NHSX could be detected. EK, Langerhans cells and melanocytes appeared morphologically unaffected by CsA and no signs of acute toxicity (giant mitochondria, vacuolization, microcalcifications) were seen. These results suggest that CsA exerts a subtle effect on human EK; indeed, despite an unequivocal antiproliferative activity, no significant histological changes related to the acute CsA toxicity seem to be induced on the various epidermal cell types.
Animals↗
The effect of cyclosporin A on proliferation and differentiation-associated antigens of normal human skin xenografted onto nude mice.
Cyclosporin A (CsA) has been shown to inhibit, in vitro, the proliferation of cultured normal and neoplastic keratinocytes and to exert also in vivo an antiproliferative effect on keratinocytes of normal human skin xenografted onto nude mice. To gain further insight into the effects of CsA on human skin we investigated the immunohistochemical expression of several epidermal proliferation- and differentiation-associated antigens in the same model: six-week-old nude mice received a xenograft of full-thickness normal human skin; six animals subsequently received a daily subcutaneous injection of 50 mg/kg of CsA diluted in olive-oil while the others received an equivalent volume of olive-oil. The rate of epidermal proliferation was evaluated through a BrdU pulse-labelling technique, and was found to be decreased by 56% in the CsA-treated epidermal xenografts as compared to the controls. The xenografts were further examined for the expression of the following antigens: Epidermal Growth Factor- and Transferrin-receptors, Ki-67, 56.5 kD keratin polypeptide, Filaggrin, Involucrin, beta 2-microglobulin, Ulex Europaeus I- and Peanut-Agglutinin-binding sites. Most of these antigens were unchanged on CsA-treated human xenografts. However, the 56.5 kD keratin polypeptide which was consistently expressed by both basal and suprabasal epidermal keratinocytes in control xenografts showed a normal expression pattern (i.e. suprabasal keratinocytes only) in three out of the six CsA-treated xenografts. These results raise the possibility that, concurrently with a cytostatic effect, CsA may also affect keratinocyte differentiation and that this effect, possibly contributes in the beneficial effect of CsA in diseases of abnormal keratinization.
Animals↗
Ultrastructural study of the skin in a case of juvenile ceroid-lipofuscinosis.
Ceroid-lipofuscinosis (CL) is a neurometabolic disorder due to an as yet unknown enzymatic deficiency. The electron-microscopic study of various organs shows a storage of a lipofuscin-like material. The ultrastructural study of clinically uninvolved skin in a typical case of juvenile CL is reported. Granular osmiophilic deposits were found in several cell types in the dermis, including fibroblasts, endothelial cells, macrophages, Schwann cells, pericytes, and muscle cells. Neither fingerprint nor curvilinear profiles could be observed. These findings demonstrate the involvement of clinically normal skin in CL and confirm the usefulness of the EM study of the skin in the diagnosis of this rare disorder.
Adult↗
Response of discoid and subacute cutaneous lupus erythematosus to recombinant interferon alpha 2a.
Ten patients suffering from discoid lupus erythematosus (DLE) or subacute cutaneous lupus erythematosus (SCLE) were treated with interferon alpha 2a. A marked improvement or clearing of cutaneous lupus erythematosus lesions was observed in eight of them. However, the response to interferon was of short duration and within a few weeks after interferon withdrawal all patients who were improved or cleared relapsed. This study suggests that interferon alpha 2a represents a new interesting approach in the treatment of DLE and SCLE. Ongoing trials will define the optimal treatment schedule for the maintenance of interferon-induced improvement of cutaneous lupus erythematosus.
Dose-Response Relationship, Drug↗
Cultured epithelia from junctional epidermolysis bullosa letalis keratinocytes express the main phenotypic characteristics of the disease.
Keratinocytes from a 1-week-old male infant with junctional epidermolysis bullosa letalis (JEBL) were grown in vitro and then grafted as multi-layered epithelia onto nude mice, to investigate whether the defect in the dermo-epidermal cohesiveness in the disease is of epidermal and not mesodermal origin. In culture, there was a birefringent ring of cells at the edges of the keratinocyte colonies and in places some cells looked as though they had been ejected from the periphery of the colony. At confluence, the multi-layered epithelia were easily detached from the culture flasks using only mechanical agitation. On microscopy the fully-differentiated epithelium on days 21, 30 and 40 after grafting sometimes showed blistering at the dermal-epidermal junction. No labelling was noted using a GB3 monoclonal antibody, that reacts with normal human keratinocytes in culture and with the dermo-epidermal basement membrane zone in normal skin. This indicates that the defect of JEBL may be reproduced in culture and also after grafting the cultured epithelial onto a wound without an epidermis. This suggests a possible role for the junctional structure recognized by GB3 in dermo-epidermal cohesiveness.
Animals↗
Recombinant interferon alpha 2a is effective in the treatment of discoid and subacute cutaneous lupus erythematosus.
Ten patients suffering from either discoid lupus erythematosus (DLE) or subacute cutaneous lupus erythematosus (SCLE) were treated with interferon alpha 2a. Eight received low or intermediate doses (18-45 x 10(6) U/week) for a short period of time (4-8 weeks), with marked improvement of skin lesions in six, an exacerbation in one patient and no change in the other. Two patients with SCLE received high doses (100-120 x 10(6) U/week) over 12 weeks, with complete clearing of the lesions in one and a marked improvement in the other. The responses were of short duration and within a few weeks of stopping treatment all who had improved or cleared relapsed. The side-effects in all the patients were fever and a flu-like syndrome which necessitated a reduction of the dose in one case. In two patients there were increases in the liver enzyme levels, but no haematological toxicity was noted.
Adult↗
Effects of cyclosporin A on cultured human epidermal keratinocytes. Growth and 5-bromo-2'-deoxyuridine incorporation.
We have studied the in vitro effect of CsA at various doses (0.5, 1, 5, 10 micrograms/ml) on the growth and 5-bromo-2'-deoxyuridine (BrdU) incorporation by cultured normal human epidermal keratinocytes (EK). CsA was found to reduce the growth of EK at all doses used after 24, 48 and 72 h in culture, but the difference with appropriate controls became statistically significant for the dose of 10 micrograms/ml after a 48- and 72-h culture. On the other hand, CsA-treated EK comprised a reduced fraction of BrdU + (S-phase) cells, the difference being statistically significant for the dose of 10 micrograms/ml at 24, 48 and 72 h. Ultrastructural examination of CsA-treated EK, despite the presence of cytoplasmic vacuoles also observed in control EK did not show signs of severe cytoplasmic or nuclear damage. These results confirm the antiproliferative effect of CsA on cultured EK and suggest that at the concentration used, CsA acts through a cytostatic rather than a cytotoxic mechanism, most likely by blocking EK in an early phase (G0/G1) of the cell cycle.
Cell Count↗
[Immunohistochemical diagnosis of malignant melanoma].
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Biomarkers, Tumor↗
[Oral hairy leukoplakia in AIDS. Histologic and ultrastructural study of 8 cases].
Oral hairy leukoplakia is a disease of the oral mucosa occurring almost exclusively in HIV-infected (mostly AIDS) patients and due to the opportunistic development of Epstein-Barr virus (EBV) within the oral epithelium. Clinically, it shows as whitish patches with a shaggy surface occurring on the lateral margins of the tongue, less frequently the buccal and labial mucosa or the soft palate. Histologically, it comprises parakeratotic hyperkeratosis, acanthosis and numerous koilocytoid cells within the stratum spinosum, i. e. cells with a pycnotic nucleus surrounded by a clear halo and pale-staining cytoplasm. Electronmicroscopy readily shows abundant Herpes-group viral particles within the upper epithelial layers. By immunohistochemistry, in situ molecular hybridization and Southern-blot EBV antigens and DNA have been demonstrated within the lesions whereas HPV and HIV are generally undetectable. In the present work we studied by light- and electronmicroscopy lesions from 8 HIV-seropositive individuals that fulfilled the clinical and histological criteria of OHL. Ultrastructural examination showed the presence in all cases of Herpes-type virions, which, in two of the cases studied by immunohistochemistry, proved to belong to the EBV. It is concluded that electronmicroscopy is a sufficiently sensitive examination to confirm the diagnosis of OHL suggested in the presence of an appropriate clinico-histological setting.
Acquired Immunodeficiency Syndrome↗
Infection of human epidermal Langerhans' cells by HIV.
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DNA, Viral↗