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Biomedical subjects

Z Ruszczak

Publications and source records attributed to Z Ruszczak.

At least 19 recordsLinked to original sources
PubMed1993

Interferons. New additions and indications for use.

Within the past few years, natural and recombinant cytokines have become available for clinical use. The broadest clinical experience exists with the interferons because these were available first. This article discusses the clinical efficiency and therapeutic value of natural and recombinant interferon-alpha, -beta, and -gamma, alone or as part of a combination therapy of skin disorders. A novel therapeutic schedule for skin tumors such as cutaneous T-cell lymphoma and malignant melanoma and for some inflammatory skin disorders are proposed.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Cytokine regulation of proliferation and ICAM-1 expression of human dermal microvascular endothelial cells in vitro.

The effects of recombinant human interleukin 1 alpha (IL-1 alpha), interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), granulocyte/macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF) on the cell proliferation and the expression of intercellular adhesion molecule-1 (ICAM-1) were assessed in cultured human dermal microvascular endothelial cells (HDMEC). IL-1 alpha and IL-1 beta stimulated the proliferation of HDMEC in a dose-dependent manner, whereas in control experiments using human umbilical vein endothelial cells (HUVEC), IL-1 alpha and IL-1 beta did not stimulate HUVEC growth. Also GM-CSF stimulated the proliferation of HDMEC, whereas IL-6 did not affect endothelial cell growth in vitro. Treatment with IL-1 alpha, IL-1 beta, and TNF markedly increased the expression of ICAM-1 on HDMEC in a time- and dose-dependent manner, in contrast to IL-6 and GM-CSF. By pre-embedding immunoelectron microscopy, membrane-bound expression of ICAM-1 was visualized with pronounced labeling in areas of microvillous cell protrusions. The TNF-induced expression of ICAM-1 on HDMEC was blocked by co-incubation with a neutralizing antibody against TNF, but not with neutralizing antibodies against IL-1 alpha, IL-1 beta, or IL-6. In addition, co-incubation of HDMEC with TNF and the retinoid compound acitretin, dexamethasone, or indomethacin did not abrogate the TNF-induced ICAM-1 expression. These results disclose IL-1 as a major, multifunctional endothelial cell-targeted cytokine and further confirm the concept that pro-inflammatory cytokines exert differential regulatory effects on dermal microvascular endothelial cell proliferation and expression of cell-adhesion molecules.

Adult↗
PubMed1991

Cultivation of human dermal microvascular endothelial cells in vitro: immunocytochemical and ultrastructural characterization and effect of treatment with three synthetic retinoids.

A new reliable and reproducible technique to culture endothelial cells from the small vessels and capillaries of human skin is introduced, and proliferation and differentiation of the growing cells are characterized. The endothelial origin of the culture cells was confirmed by light- and electron microscopy and by labelling with Ulex europaeus Agglutinin I and an antibody against Factor VIII-related antigen. Further immunocytochemical characterization showed that 92-100% of the cells were positive for beta 2-microglobulin and the entire cell population expressed vimentin, whereas cytokeratins, desmin, HLA-DR antigen, Leu 6 and S 100 protein, could not be detected. As vascular endothelium is a common site of inflammation and retinoids have been shown to be of good clinical efficacy in some chronic inflammatory skin diseases, we investigated the influence of etretinate, etretin and isotretinoin on proliferation and antigen expression of our culture cells. All retinoids applied inhibited proliferation of endothelial cells in a dose- and time-dependent manner whereas they induced neither HLA-DR nor intercellular adhesion molecule-1 (ICAM-1). Furthermore, none of the retinoids applied influenced the gamma-interferon-induced expression of these surface antigens on endothelial cells. Our results suggest that the action of retinoids in skin inflammation is not mediated by modulation of HLA-DR or ICAM-1. The cell culture technique described here is an interesting and reliable model for studying the influence of drugs on endothelial cell growth and differentiation in vitro.

Acitretin↗
PubMed1991

Long-term therapy of HIV-associated Kaposi's sarcoma with recombinant interferon alpha-2a.

Five young male patients with HIV-associated Kaposi's sarcoma (KS) were treated with recombinant interferon alpha 2a (rIFN-alpha-2a) over a period of 2-2.5 years. An IFN dose of 18 x 10(6) IU was given subcutaneously every day during the first 3 months of treatment and then on alternate days. Additional treatment with radiotherapy and laser therapy was given and, in some cases, isolated skin nodules were excised. Within 7 months of initiation of therapy one patient had a complete remission of his tumours, however, tumour progression recurred after the patient discontinued treatment. In another patient the tumour cleared within 9 months of rIFN therapy, and after 52 months he is still free of KS. The condition of a third patient tended to become stabilized during the first 6 months of therapy, but after 60 months there has been a slow progression. The fourth and fifth patients died 25 and 28 months, respectively, after the histological diagnosis of KS and the initiation of treatment. While on therapy with rIFN-alpha-2a, no life-threatening opportunistic infections occurred. The side-effects were mostly well tolerated, and no severe changes in haematological parameters were caused by the therapy.

Adult↗
PubMed1990

Effects of rIFN alpha, beta, and gamma on the morphology, proliferation, and cell surface antigen expression of human dermal microvascular endothelial cells in vitro.

The influence of recombinant human interferon alpha 2a (rIFN alpha), recombinant human interferon beta 1 (rIFN beta), and recombinant human interferon gamma (rIFN gamma) on human dermal microvascular endothelial cells (HDMEC) cultured in vitro was studied in various rIFN concentrations (0.1 IU/ml-10(4) IU/ml) over 2, 3, 4, 6, 8, and 10 d. Cell morphology and ultrastructure, cell proliferation, expression of class II alloantigens (HLA-DR and HLA-DQ), and intercellular adhesion molecule-1 (ICAM-1) were investigated using an in vitro technique established in our laboratory. All rIFN tested induced alterations of typical HDMEC morphology; the cells became spindle-shaped and fibroblastoid, although they maintained their endothelial cell marker expression. Also, all IFN dose- and time-dependently inhibited the proliferation of HDMEC in vitro (rIFN alpha greater than beta greater than gamma), whereby rIFN alpha exerted the strongest growth-inhibitory effect. Alkaline phosphatase anti-alkaline phosphatase (APAAP) immunocytochemistry of the cultured cells showed dose- and time-dependent stimulation of ICAM-1 and class II antigen expression only by rIFN gamma (HLA-DR greater than HLA-DQ), rIFN alpha and beta did not exert any immunomodulatory activity on HDMEC in vitro. These results indicate that HDMEC are an important target for the action of IFN. Besides growth inhibition, it seems that rIFN gamma in particular may be involved in the modulation of leucocyte adhesion and trafficking by altering the immunophenotype of the endothelial cell population.

Antigens, Surface↗
PubMed1990

Effects of recombinant tumor necrosis factor-alpha on cultured microvascular endothelial cells derived from human dermis.

We investigated the effects of recombinant human tumor necrosis factor-alpha (TNF) on cell proliferation and on expression of MHC class II antigens and intercellular adhesion molecule ICAM-1 in human dermal microvascular endothelial cells (HDMEC) derived from human foreskin. Second-passage HDMEC were treated with 0.1-10,000 U/ml TNF for up to 6 d, and cell growth was assessed by cell counts and a recently developed fluorogenic assay using 4-methylumbelliferyl heptanoate as a substrate. APAAP immunocytochemistry was performed using monoclonal antibodies against HLA-DR, HLA-DQ, and ICAM-1. TNF did not markedly inhibit the growth of HDMEC but induced expression of HLA-DR (1,000 U/ml and more) and of ICAM-1 (1 U/ml and more). Combination with interferon-gamma led to synergistic ICAM-1 induction. These results demonstrate a profound effect of TNF on the activation of dermal microvascular endothelial cells and suggest a major role of TNF in the mediation of leucocyte adhesion to endothelial cells of the skin microvasculature with possible implications for the initiation and maintenance of inflammatory skin processes.

Cell Adhesion Molecules↗
PubMed1990

[Preliminary findings on lectin binding in human follicular epithelium].

Glycoconjugates in the cell membranes of the outer and the inner root sheath of human anagen hair follicles were histochemically characterized by means of the following lectins: UEA-I, DBA, PNA, WGA, SBA, RCA, and Con A (avidin-biotin technique, counter-staining with methyl green). We observed intense labeling of the outer root sheath with UEA-I, DBA, Con A, and PNA, whereas the other markers were only weakly positive. VEA-I, DBA and SBA labeling was confiried to the upper two thirds of the outer root sheath. As to the inner root sheath, we found intense labeling with UEA-I, WGA, RCA, and SBA; all other lectins were only weakly represented. Our results suggest that the cell membranes of the outer and inner root sheaths of human hair follicles are characterized by the prevalence of different glycoconjugates; moreover, labeling with UEA-I, SBA, and DBA is obviously related to the process of differentiation within the follicle.

Cell Differentiation↗
PubMed1990

[Kyrle disease in juvenile diabetes mellitus and chronic renal failure].

We report on a 32-year-old female patient with chronic diabetes mellitus, type I, and chronic renal failure, who developed the typical clinical picture of hyperkeratosis follicularis et parafollicularis in cuteum penetrans (Kyrle's disease) within one year. Histological examination revealed a defective epidermal differentiation with hyper- and parakeratosis as well as premature keratinization as early as in the epidermal basal cell layer. Studies on lectin binding showed that the glycosylation process was impaired in both the epidermis and the basement membrane zone of the lesional skin. In addition, electron microscopic investigation revealed diabetic microangiopathy of the dermal vessels as well as marked ultrastructural alterations of the dermo-epidermal basal lamina. These findings confirm the association of diabetes mellitus with Kyrle's disease previously described; they make us suggest that Kyrle's disease might be characterized by a defective differentiation of the epidermis and the dermo-epidermal junction--due to some alteration of the underlying glycosylation processes--rather than by a local disorder of keratinization. Regarding the clinical manifestation of the disease, both diabetes mellitus and chronic renal failure may play a part as precipitating factors.

Adult↗
PubMed1988

[Lymphocyte transformation test following stimulation with a protein factor from neutrophilic granulocytes (PMNL) in psoriasis patients].

The lymphocyte transformation test (LTT) was given to 20 healthy subjects and 43 patients with generalized psoriasis vulgaris: it was given right after stimulation with PHA (spontaneous) and after stimulation with allogenic and autogenic protein factor (NPF). NPF was isolated from secondary lysosome granules of peripheral blood neutrophils. The results were analyzed using computer statistic tests. No distinct differences were noticed between the spontaneous transformation test in psoriatic patients compared to the controls. After stimulation with PHA, the percentage of blast cells was significantly lower in patients with psoriasis. When allogenic and autogenic NPF was used for stimulation, the LTT values were significantly higher in the psoriasis group than in the control subjects. This fact points out the increase in sensitivity of lymphocytes to NPF in active psoriasis and the possibility of abnormal neutrophil-lymphocyte interactions in vivo. This phenomenon may be intensified when under the influence of bacterial or viral agents, or medicaments; the degranulation of secondary lysosome granules of neutrophils occurs, causing the release of NPF. These investigations support our opinion that psoriasis is a systemic disease and that NPF plays a considerable role in the psoriatic reaction.

Adult↗
PubMed1987

[Leukocyte migration test following stimulation with protein factor of neutrophilic granulocytes (PMNL) in the peripheral blood of patients with psoriasis].

Blood investigations were performed in 43 patients suffering from generalized psoriasis vulgaris and 40 healthy test persons. The results were statistically evaluated with the help of the computer technique. In the patients with active psoriasis, we found stimulation of the leucocyte migration caused by the autogenic protein factor from the peripheral blood PMNL. In addition, we observed that a mechanism like this may occur in vivo under the influence of biological degranulation factors (bacterial antigens from intraorganic infection foci). The mechanism described ist likely to act in an autoimmunostimulating way on immunologic reactions and is one of the elements which stimulate the PMNL activity in psoriatics. These results support our opinion that psoriasis is a systemic disease and indicate the role of the PMNL protein factor regarding the development of the psoriatic reaction.

Adolescent↗
PubMed1987

Angioproliferative changes in clinically noninvolved, perilesional skin in AIDS-associated Kaposi's sarcoma.

In clinically noninvolved skin from the area surrounding early macular lesions of AIDS-associated disseminated Kaposi's sarcoma (KS), morphological evidence of vascular proliferation was seen in the upper papillary dermis. Poorly differentiated cells with cytoplasmic inclusions similar to Weibel-Palade bodies were found to form primitive vascular lumina. Around the vessels, dermal Langerhans' cells and lymphoid cells were detected. Spindle-shaped cell proliferation characteristic of fully developed KS lesions was not observed. The angioproliferative changes, undetectable clinically, were similar, though less evident, to those observed in early lesions of disseminated KS, but without stroma tissue reaction. These findings suggest that in AIDS-associated KS angioproliferation may not be restricted to the clinically detectable lesions and that some angioplastic factor(s) may cause widespread endothelial hyperproliferation.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Kaposi's sarcoma in AIDS. Multicentric angioneoplasia in early skin lesions.

Light-microscopic, immunohistochemical, and ultrastructural studies were performed on biopsy material from 15 young homosexual men with AIDS-associated mucocutaneous Kaposi's sarcoma; 19 Kaposi's sarcoma lesions in different developmental stages were investigated. These lesions showed multicentrically arising and proliferating vascular endothelia forming thick-walled and thin-walled capillaries and larger vessels, as well as spindle-shaped cells forming fascicles and bundles around them. Different amounts and organization of these two major cellular components were found in all stages of evolution of Kaposi's sarcoma lesions. Immunohistochemical and electron-microscopic techniques suggested that the spindle-shaped cells were of pericyte origin in different stages of maturation or, more rarely, lymphatic endotheliocytes. The skin lesions of AIDS-associated Kaposi's sarcoma occurred as a result of multicentric angioneoplasia of rather slow progression, together with the proliferation of pericyte-like mesenchymal cells, possibly representing a stromal reaction to the vascular proliferation. Both blood and lymphatic vessels seemed involved in this process. In early stages, scattered lymphocytic infiltration was an additional feature. Mitotic figures and cytologic atypia were not seen more frequently in early AIDS-associated Kaposi's sarcoma than in proliferating granulation tissue.

Acquired Immunodeficiency Syndrome↗
PubMed1986

[Humoral and cellular immune response in psoriasis].

Several immunological reactions (immunoglobulin levels in the blood serum, lymphocytic stimulation, migration of leucocytes etc.) were examined in the blood serum of psoriatics before and after treatment and compared with control. Abnormal reactions were even seen in psoriatics after successful treatment. As far as these data reveal, psoriasis is a systemic disorder.

Adolescent↗
PubMed1983

[Goniometric studies of the human placental barrier in late pregnancy in EPH gestosis].

The structure of normal and toxemic pregnancy (EPH-gestosis) placenta was analysed by goniometric observation. Hitherto the most characteristic symptom of gestotic placenta demonstrable by measurements appeared to be thickening of the placental basallayer consisting of the basal membranes of the capillary endothelium and syncytiotrophoblast. Observations were now made on 20 normal placentas and on 20 ones with full-clinical gestotic symptoms. Specimens prepared by conventional methods were examined with a Philips EM 300 electron microscope, equipped with a goniometer stage. Measurements of the placental basal layer in three goniometer positions: 0 degrees, + 45 degrees, - 45 degrees, were made from negatives of electron micrographs with a final magnification 135,200 x. Data were analysed statistically using Wilcoxon's test. We also used the planimetric-statistic method of Casley-Smith and Davy. We found the thickness of the gestotic placental basal layer to be significantly less than in a normal one. Ultrastructural markers of transport through the feto-maternal blood barrier were more evident that in normals. We suppose the increased placental transport and decreased thickness of the placental basal layer could be compensatory reactions to the pathological lesions of gestotic pregnancy.

Basement Membrane↗