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Biomedical subjects

J Kanitakis

Publications and source records attributed to J Kanitakis.

At least 163 records · Page 9Linked to original sources
PubMed1989

[Immunohistochemical identification in skin tumor pathology].

Immunohistochemical methods play a very prominent role in the histological diagnosis of skin diseases. Their field of practical application, which initially was limited to patients with signs of autoimmunization, now includes several other nosological entities in dermatological histopathology, and particularly tumours. By using monoclonal or polyclonal antibodies, it is now possible to establish the diagnosis of poorly differentiated tumoral proliferations, such as carcinomas, melanomas, sarcomas, lymphomas, etc., to classify lymphomas according to their differential membrane antigens, or even to determine the histogenetic origin of tumours of unknown nature.

Antibodies, Monoclonal↗
PubMed1989

Immunohistochemical study of normal skin of HIV-1-infected patients shows no evidence of infection of epidermal Langerhans cells by HIV.

Langerhans cells (LC) are dendritic epidermal antigen-presenting cells expressing the surface molecule CD4, which renders them theoretical cellular targets for direct infection by the human immunodeficiency virus (HIV). To date, somewhat conflicting results have been reported concerning the in vivo infection of LC by HIV as well as the numerical alteration of these cells in the course of HIV infection. In the present work we studied clinically normal skin of a group of 44 HIV-1-seropositive patients classified according to the Centers for Disease Control (CDC) stages II (n = 14), III (n = 9), and IV (n = 21). Monoclonal antibodies (MAb) to HIV p18, p24, and gp120 and to HLA-DR and CD1a antigens (specific for LC) were applied on frozen skin sections using an amplification biotin-streptavidin-fluorescein technique. The MAb to HIV p18 cross-reacted with a cytoplasmic antigen of epidermal basal keratinocytes also present on HIV-seronegative skin specimens. No other reactivity was observed with any of the three anti-HIV MAb. The quantitative study showed that no significant correlations could be established between the number of LC (evaluated independently by HLA-DR and CD1a antigens) and the number of peripheral blood CD4+ve lymphocytes or the CDC disease stage. These results cast some doubt on the previously reported in vivo infection and numerical decrease in LC in HIV infection. The precise involvement of LC in HIV infection awaits further investigation.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Cyclosporin A inhibits directly in vivo keratinocyte proliferation of living human skin.

A direct in vivo antiproliferative effect of cyclosporin A (CsA) on human epidermal keratinocytes (EK) grafted onto nude mice was evaluated. Using pulse-labeling of 5-bromo-2'-deoxyuridine (BrdU), a thymidine analogue incorporated into the nuclei of DNA-synthesizing (S-phase) cells, the antiproliferative effect of CsA was revealed as a decrease in the number of BrdU-positive human EK grafted onto nude mice receiving a daily subcutaneous injection of 50 mg/kg of CsA. The blood level of CsA in the treated mice, evaluated by a radioimmunologic assay, was 679 +/- 501 ng/ml (n = 3). Using an antibody to leukocyte common antigen, it was shown that no human lymphocytes were present in the grafted skin. Therefore, this antiproliferative effect of CsA on human EK seems to be due to a direct effect on EK rather than to lymphocyte regulation.

Animals↗
PubMed1989

Distribution of an estrogen receptor-related protein (P29) in normal skin and in cultured human keratinocytes.

A monoclonal antibody, ERD5, which recognizes a 29Kd phosphoprotein associated with human estrogen receptor of myometrium was used to study the expression of this protein in normal skin and in cultured human keratinocytes. By indirect immunofluorescence, both in vivo and in vitro keratinocytes showed a variable cytoplasmic staining which increased with cell differentiation. SDS gel electrophoresis of soluble extracts of cultured keratinocytes and normal epidermis showed that P29 was a minor protein. Immunoblot analysis demonstrated that ERD5 strongly reacted only with a 29Kd polypeptide band without any cross-reactivity. These data suggest that keratinocytes might be estrogen sensitive like other cells in which P29 has already been located. The exact role of this protein in the keratinocyte differentiation process and its relationship with estrogen receptors remain to be elucidated.

Adolescent↗
PubMed1989

Expression of an estrogen receptor-associated protein (p29) in epithelial tumors of the skin.

p29 is a cytoplasmic serine phosphoprotein of 29 kD MW, closely linked to estrogen receptors. In this work we studied the expression of p29 protein in normal human skin and a group of cutaneous benign and malignant tumors by using a monoclonal antibody (ERD5) that specifically recognizes p29. In normal skin, p29 reactivity was observed in epidermal and some adnexal keratinocytes, as well as in smooth muscle cells of dermal arterioles and arrector pili muscles. p29 was also detected in most, but not all, epithelial tumors studied. The expression of p29 was generally stronger in the more differentiated (keratinized) normal and neoplastic keratinocytes; however, no correlation could be noted between immunochemical staining for p29 and either benignity of the lesion or sex of the patient considered. Whereas, in breast cancer, the expression of p29 is reported to correlate with endocrine response, the precise relationship between epithelial tumors of the skin and the action of estrogens remains to be elucidated.

Adult↗
PubMed1989

Nonimmunosuppressive ciclosporin H inhibits the growth and DNA synthesis of cultured normal human epidermal keratinocytes.

Ciclosporin H (CsH) is an epimer (11-D-N-methyl-L-valine) of ciclosporin A (CsA) devoid of immunosuppressive properties. The known antiproliferative effect of CsA on epidermal keratinocytes (EK) grown in vitro prompted us to study the effect of CsH (at the doses of 0.5, 1, 3.5 and 5 micrograms/ml) on the growth and DNA synthesis (5-bromo-2'-deoxyuridine incorporation). CsH was observed to reduce both the number and DNA synthesis of EK in a statistically significant manner at the dosage of 5 micrograms/ml after 24, 48 and 72 h in culture. These results show that the immunosuppressive properties of the ciclosporins (Cs) are dissociated from the antiproliferative ones on EK and highlight the interest of further in vivo studies that may lead to therapeutic applications of Cs in hyperproliferative epidermal diseases requiring no immunosuppression.

Bromodeoxyuridine↗
PubMed1989

Cyclosporin A does not modify Langerhans' cell number and distribution in normal human skin.

We used the model of human skin graft on nude mouse to investigate a possible influence of systemically administered cyclosporin A (CsA) on epidermal Langerhans' cells (LC). This experimental model has the advantage of being independent of the systemic humoral and cellular influences of a human host. No change in the human LC distribution or number could be observed after 3 weeks of CsA therapy as revealed by anti-CD1 and anti-HLA-DR immunohistochemical stainings and the cell counting, despite the evidence of the drug effect on the keratinocyte proliferation. However, our findings do not rule out the possibility that CsA influences the LC functional capacities responsible for the local cell-mediated immunity responses.

Animals↗
PubMed1989

[Filaggrin].

Cells in the granular layer of mammalian epidermis contain densely staining bodies called keratohyalin granules. Two types of granules are identified. Larger ones contain phosphorus and consist largely of an unusually histidine rich protein. This protein has a high molecular weight and contains a large fraction of basic aminoacids. However it has a neutral isoelectric point due to extensive phosphorylations. This histidine rich protein undergoes modifications during terminal differentiation, especially when the keratohyalin granules disperse as the granular cells differentiate into the overlying cornified cells. At this point it is dephosphorylated and partially proteolyzed to form lower molecular weight highly basic histidine rich proteins. These cationic molecules aggregate in vitro with keratin intermediate filaments, forming well ordered macrofibrils whose structure resembles the keratin pattern seen in the lower cornified layers. For this reason the name filaggrin is used for these proteins. The high molecular weight precursor is called profilaggrin. Filaggrins are species-distinct products and consist of a number of isoelectric variants. It is established that the filaggrin precursor is composed of tandemly linked multiple copies of filaggrin domains interspersed with short linker peptides. Two functions are proposed for the filaggrin. The first one, based on its interaction with keratin fibres in vitro, is to form the interfilamentous matrix seen in the lower stratum corneum. The second one is to generate a concentrated pool of free aminoacids and derivatives, allowing the stratum corneum to remain hydrated at low environmental humidities. These functions represent sequential rather alternative roles. Epidermal diseases and in vitro cultures illustrate the clear-cut relations between epidermal keratinization and differentiation and the histidine rich proteins pathway.

Animals↗
PubMed1988

Congenital self-healing histiocytosis (Hashimoto-Pritzker). An ultrastructural and immunohistochemical study.

Congenital self-healing histiocytosis (CSHH) is a rare primary histiocytic skin disorder. Only a few cases have been studied by ultrastructure and immunohistochemistry. Here we report a new case that was investigated using an electron microscope and a panel of monoclonal (MCA) and polyclonal (PCA) antibodies. CSHH cells were found to bear the immunohistochemical phenotype of normal epidermal Langerhans cells (LC) and histiocytosis X (HX) cells (CD1a/c+, CD1b-, CD4+/-, human leukocyte antigen [HLA]-DR/DQ+, S-100+). However, an electron microscope showed a paucity of Birbeck granule (BG)-containing cells. This contrasted with their immunophenotype. This finding, along with other ultrastructural characteristics of CSHH cells, suggests that histologic differences exist between CSHH and HX. However, because no absolute histologic criterion is known that allows unequivocally the differential diagnosis between the two diseases, this distinction currently has to rely on clinical criteria, mainly the regressive course observed within a few months in CSHH. The precise nosologic position of CSHH among other histiocytic syndromes remains unsettled.

Antibodies, Monoclonal↗
PubMed1988

Filaggrin expression in normal and pathological skin. A marker of keratinocyte differentiation.

Filaggrin is a basic, histidine-rich protein synthesized by cells of keratinizing epithelia, that subserves major physiological functions in maturating epidermis. Its precursor, profilaggrin, constitutes a major component of kertohyalin granules. In this work the expression of profilaggrin/filaggrin was studied in 140 specimens of normal human adult and fetal skin, cultured epithelia before and after allo- and xeno-grafting, and several cases of keratinization disorders and tumours. An avidin-biotin-alkaline phosphatase technique was applied on deparaffinized tissue sections, by using a specific monoclonal antibody (AKH1) to profilaggrin/filaggrin. The results show that the expression of profilaggrin/filaggrin is variously altered in keratinization disorders, whereas in epithelial proliferations it seems to decrease with an increasing degree of dedifferentiation of the tumour. Therefore the expression of these antigens can be considered to be a sensitive marker of maturation of normal epidermis and provides a new tool for the study of differentiation of the surface epithelium in skin diseases.

Fetus↗
PubMed1988

Treatment of nine cases of pemphigus vulgaris with cyclosporine.

The effects of cyclosporine were studied in nine patients suffering from pemphigus vulgaris. Of four patients treated with cyclosporine alone, only one cleared. Of four corticosteroid-resistant pemphigus vulgaris patients, all improved after cyclosporine addition to corticosteroids. The last patient treated from the beginning with a combined treatment (cyclosporine-corticosteroids) did not respond. The main advantage of using cyclosporine is to allow a decrease in corticosteroid dosages and to permit treating corticosteroid-resistant pemphigus vulgaris patients. No detectable irreversible side effects were noted. The treatment was discontinued in two patients because of reversible side effects. Cyclosporine alone does not seem to be an adequate treatment of the acute phase of pemphigus vulgaris but could be used in addition to corticosteroids. The most important drawback of cyclosporine treatment is the occurrence of clinically silent renal dysfunction (tubular involvement and interstitial fibrosis), which may occur during long-term treatments. More studies need to be carried out to determine the effects of low doses of cyclosporine on renal function in patients who have normal renal functions.

Administration, Oral↗
PubMed1988

Epithelial differentiation of human skin equivalents after grafting onto nude mice.

Human skin equivalents were developed in vitro with a unidimensionally retracted dermal equivalent made of human type I + III collagen and human MRC5 fibroblasts, and a multilayered epithelium grown in liquid medium from normal human keratinocytes in suspension. We investigated the degree of epidermal differentiation that could be achieved after in vivo grafting onto nude mice by means of light and electronmicroscopy as well as by immunohistochemistry. All transplanted grafts showed a primary take. The grafts formed an epidermis with a stratum corneum and from day 7 to 14 after transplantation a distribution of a 56.5 Kd keratin protein, involucrin, profilaggrin/filaggrin, and MHC-I antigens that was similar to what is noted in normal human epidermis. These data indicate that a full terminal differentiation was only achieved after in vivo transplantation of the cultured epithelium. Pigmentation was present, but no marker of Langerhans cells was seen at 4 weeks. Although there was no evidence of the dermal equivalent after 2 weeks, we noted a strong adherence of the graft to the wound bed, with the presence of type-IV collagen, laminin, and bullous pemphigoid antigen at the dermo-epidermal junction (day 7) and hemidesmosomes, a lamina lucida and a lamina densa (day 30). No epithelial damage was noted in spite of an inflammatory infiltrate in the underlying tissue. This represents a preliminary step in the use of such a skin-equivalent in the treatment of human patients with wounds.

Animals↗
PubMed1988

The expression of PNA-lectin binding sites and S-100 protein in histiocytic lesions of the skin. A comparative immunohistochemical study.

In this work the potential usefulness of antibodies to S-100 protein and the lectin Peanut Agglutinin (PNA) in the differential diagnosis of histiocytic lesions of the skin was assessed. Out of 54 deparaffinized specimens studied through an avidin-biotin-alkaline phosphatase technique, 35 proved to comprise S-100 (+) and 12 PNA (+) cells. The results show that antibodies to S-100 protein are useful in distinguishing the "X" (Langerhans' cell) from the "non-X"types of histiocytosis, and cast some shadow on the usefulness of the lectin PNA as a histiocytic marker. (Received May 5, 1987.)

Arachis↗