Search PubMed⌕ Search

Biomedical subjects

Z Ruszczak

Publications and source records attributed to Z Ruszczak.

At least 19 recordsLinked to original sources

Update on tissue-engineered biological dressings.

Tissue-engineered biological dressings offer promise in the treatment of burns, chronic ulcers, donor site and other surgical wounds, and a variety of blistering and desquamating dermatologic conditions. For example, the prevalence of diabetic foot ulcers ranges from 4.4% to 10.5% of diabetics, resulting in 82,000 lower extremity amputations annually; venous leg ulcers affect 0.18% to 1.35% of the population; and pressure ulcers are found in 5.0% to 8.8% of institutionalized patients and 14.8% of patients in acute care facilities. Despite the large number of potential beneficiaries, cellular tissue-engineered products have suffered setbacks in recent years and have garnered considerably lower market share than commercial promoters anticipated. The mechanism of action of these products is not universally agreed upon, but delivery of growth factors and extracellular matrix components to the wound is thought to be important; graft "take" is not usually considered to occur. These "engineered" products do not specifically match a treatment modality to an underlying pathology. Clinical effect is often modest, and sometimes not justi- fiable from a cost-benefit perspective. Nevertheless, clinical reports in the literature of uses of tissueengineered biological dressings continue to mount, indicating that these products are finding niche applications where clinical utility is high and the cost can be defended. Despite commercial setbacks, the first-approved products, Dermagraft, Apligraf, and Cultured Epidermal Autograft (Epicel) are still being marketed, and new ones, such as OrCel, continue to be developed. The major indications for these products are summarized and a brief review of the available clinical literature is offered.

Biological Dressings↗

Pyoderma vegetans.

BACKGROUND: Pyoderma vegetans is a rare condition that is clinically characterized by large verrucous plaques with elevated borders and multiple pustules. The etiology of this disorder remains unknown. OBJECTIVES: We describe a 24-year-old woman with rapidly evolving pyoderma vegetans. Our patient had the unique additional findings of a highly elevated serum IgE level and a history of hidradenitis suppurativa. CONCLUSIONS: Pyoderma vegetans is diagnosed on clinical and histological criteria. Differentiation must be made from disorders such as pyoderma gangrenosum, Sweet's syndrome, and deep fungal infections. We illustrate a case of pyoderma vegetans and review the literature on this rare disorder. Clinical and histological criteria for diagnosis are presented, as well as differentiation from some mimicking disorders.

Adult↗

Penile Kaposi's sarcoma preceded by chronic penile lymphoedema.

Kaposi's sarcoma localized to the penis with striking lymphoedema is extraordinary. We report a middle-aged Haitian man who was human herpesvirus-8 seropositive, without evidence of immunosuppression or human immunodeficiency virus infection. He was first seen with Kaposi's sarcoma of 6 months duration localized to his penis, preceded by a 3-year history of chronic penile lymphoedema. His tumour regressed completely after radiotherapy. We propose that chronic lymphoedema in this patient predisposed to the development of Kaposi's sarcoma.

Humans↗

Modern aspects of wound healing: An update.

Wound healing is an area of cutaneous medicine in which there have been many recent advances. Interest has focused on the development of an in vitro reconstructed skin, although neither the commercially available products nor the products currently described in experimental studies are able to fully substitute for natural living skin. The substitution of the main component of each wound, the connective tissue matrix, is an advance. Once dermis is reconstructed, the covering of the wound surface with both in vitro expanded epidermis and autologous split-skin transplants is significantly easier and has an improved chance of success. Epidermal stem cells may facilitate functionality of the superficial part of such a system. New experimental and clinical trials are currently under way.

Animals↗

Collagen uses in dermatology - an update.

Collagen-derived materials have been used in medicine for many decades. Sutures, hemostatic devices and matrices which stimulate cell growth and soft tissue augmentation are the major applications. In this update, we discuss the two major applications for collagen in dermatology: tissue augmentation and wound healing.

Animals↗

Vascular endothelium in the regulation of immune response.

Endothelial cells cover the entire system of arteries, veins, and lymphatics of the human body. Once viewed as a passive coat, we now know that they represent by themselves a large immunologically active system. In this work, we briefly review endothelial cell models and heterogenicity before interrelating endothelial cells with the immune system. In the latter context, we focus on the role of cytokines and that of the five families of cell adhesions molecules.

Cell Adhesion Molecules↗

Kaposi's sarcoma limited to penis treated with cobalt-60 radiotherapy.

We report a 78-year-old German man of neither Mediterranean nor Jewish lineage who developed Kaposi's sarcoma localized to his penis. An evaluation for retrovirus infection or other causes of immunosuppression was negative. The nodules responded to radiotherapy with cobalt-60, rapidly involuting. The patient has no evidence of Kaposi's sarcoma for over two years.

Aged↗

Therapeutic guidelines in vasculitis.

For the treatment of cutaneous vasculitis it is of considerable importance to distinguish clinically between vasculitis as primary disease or as secondary process due to a systemic disease. This implies a thorough diagnosis of the patient to classify the individual case. The currently available therapy of cutaneous vasculitis is rarely causative. In most cases a symptomatically orientated antiinflammatory immunosuppressive therapy is used to control the disease. In this review we will report on the currently used therapy protocols in cutaneous vasculitis.

Humans↗

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↗

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↗

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↗

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↗

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↗

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↗

[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↗

[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↗