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Biomedical subjects

W Sterry

Publications and source records attributed to W Sterry.

At least 217 records · Page 12Linked to original sources

["Granulomatous slack skin"--cutaneous elastolytic lymphoma].

The term "granulomatous slack skin" (GSS) was introduced by Ackerman for a disease first described by Convit et al. in 1973. GSS represents a rare cutaneous lymphoma characterized by localized elastolytic lesions with a granulomatous infiltrate. We recently observed two male patients with the characteristic features of this disease. Both patients responded well to therapy with interferon-alpha 2b. In one patient clinical remission was stable under long-term treatment with clofazimine. We report on common features of these two patients and give a review of the cases published in the literature.

Biopsy↗

Kiwi fruit allergy: a new birch pollen-associated food allergy.

BACKGROUND: To determine the cross-reacting antigens of kiwi fruit and other foods and pollen, we investigated 22 patients allergic to kiwi fruit: 10 with severe systemic reactions and 12 with localized symptoms confined to oral and pharyngeal mucosa (oral allergy syndrome). Seven patients with birch pollen allergy who tolerated kiwi fruit were included as a control group. METHODS: All patients were evaluated by skin testing and RAST; three patients were evaluated by RAST inhibition assays. RESULTS: Prick tests showed positive reactions to kiwi fruit in all patients, whereas specific IgE to kiwi fruit could be demonstrated only in patients with generalized severe symptoms. Surprisingly, all 22 patients with clinical kiwi allergy showed positive prick test results and elevated IgE to birch pollen. Clinically, all complained of rhinitis during birch pollen season. Many patients showed sensitization to grass and mugwort pollen. Also, food allergy was found to be associated with kiwi allergy: we found strong reactions to apple and hazelnut; moderate reactions to carrot, potato, and avocado; and weak reactions to wheat and rye flour, pineapple and papaya, and their enzymes bromelain and papain. RAST inhibition studies revealed cross-reacting antigens between birch pollen and kiwi fruit. Interestingly, patients with birch pollen allergy without clinical signs of kiwi allergy had positive prick test reactions to kiwi. Patients with kiwi allergy showed higher concentrations to birch pollen IgE compared with patients with isolated birch pollen allergy. CONCLUSIONS: Our results indicate that kiwi allergy is a new manifestation of birch pollen-associated food allergy and is mediated by cross-reacting antigens in the kiwi fruit. Kiwi allergy can be expected in patients with birch pollen allergy exhibiting high levels of IgE to birch pollen.

Adolescent↗

Recurrent chromosome abnormalities in peripheral T-cell lymphomas.

Cytogenetic findings in 45 cases of peripheral T-cell lymphomas (PTL) diagnosed according to the updated Kiel classification are reported. Recurrent numerical chromosome aberrations comprised -X, -Y, -13, +X, +3, +5 and +7. Recurrent structural aberrations included t/del(1)(p31-32), t(2;5)(p23;q35), dup(5)(q23q31-32), t/dup(6q), t/del(6q), trisomy 7q, and trisomy 8q, mostly due to i(8)(q10), and changes in 14q11 and 14q32.1, mostly due to inv(14)(q11q32.1), t/del(13)(q14), t(6;7)(q13;q13), and t(13;17)(q11-13;p11). All deletions in 6q involved band 6q21 and all partial trisomies of 7q led to an amplification of band 7q21. Further studies are needed to ascertain whether these cytogenetic findings in PTL are of clinical and prognostic significance.

Adolescent↗

Analysis of TAP2 and HLA-DP gene polymorphism in psoriasis.

TAP2 is a gene, located between HLA-DP and HLA-DQ, whose products form a transporter molecule involved in endogenous antigen processing. Polymorphic residues have been described in this gene. TAP2 is of particular interest because its involvement in antigen presentation makes it a candidate for a disease susceptibility gene. In psoriasis, two clinical subtypes analogous to the situation in diabetes type I with early onset and family history and type II with later onset and without family history have been described. We have previously shown that type I but not type II psoriasis is associated with the HLA-DRB1*0701/2, -DQA1*0201, -DQB1*0303 haplotype. To investigate whether this haplotype extends to include particular TAP2 and/or DP alleles, we tested the TAP2 and HLA-DP alleles of a control group (n = 199), patients with psoriasis type I (n = 66), and patients with psoriasis type II (n = 35) by hybridization with SSOs. Our data show that there is no significant correlation between TAP2 and/or HLA-DP gene polymorphism and psoriasis type I and/or type II. We conclude that disease association in type I psoriasis is associated with the extended haplotype HLA-B57, -Cw6, -DRB1*0701/2, -DQA1*0201, -DQB1*0303.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Expression of the B7/BB1 activation antigen and its ligand CD28 in T-cell-mediated skin diseases.

Interactions of CD28 (on T cells) with its recently identified ligand B7/BB1 (on antigen-presenting cells) have been shown to activate T cells via a major histocompatibility complex/Ag-independent "alternative" pathway, leading to an amplification of T-cell-mediated immune responses. The in vivo relevance of these molecules for cutaneous immunity is presently unknown. These findings prompted us to study the expression of B7/BB1 and CD28 in normal human skin and in selected T-cell-mediated inflammatory skin diseases. Biopsies were obtained from lesional skin of patients with allergic contact dermatitis, lichen planus, and, as control, from basal cell carcinoma and from healthy controls. Serial cryostat sections were stained with a panel of MoAbs directed against CD28, B7/BB1, CD3, CD1a, and KiM8 using immunohistochemistry (ABC technique). CD28 expression was observed in the majority of dermal and epidermal CD3+ T cells in contact dermatitis and lichen planus. In normal skin and basal cell carcinoma, CD28 was expressed only occasionally by perivascular T cells. In allergic contact dermatitis and lichen planus, B7/BB1-expression was found on dermal dendritic cells, on dermal macrophages, on Langerhans cells, focally on keratinocytes, and occasionally on dermal T cells. No B7/BB1 immunoreactivity was detected in normal skin and basal cell carcinoma. These findings indicate that T-cell-mediated skin diseases are accompanied by an influx of CD28+ T cells and an upregulation of B7/BB1 on cutaneous antigen-presenting cells, keratinocytes, and on some T cells. We speculate that "alternative" T cell-activation via the B7/CD28 pathway may contribute to the pathogenesis of these skin diseases.

Antibodies, Monoclonal↗

Evidence for a pathway independent from 2'-deoxyguanosine and reversible by IL-2 by which purine nucleoside phosphorylase inhibitors block T-cell proliferation.

Patients with homozygous deficiency of purine nucleoside phosphorylase (PNP) present with a T-cell selective immune deficiency. To elucidate the potential use of PNP inhibitors in the therapy of cutaneous T-cell lymphomas (CTCLs) the authors studied the effects of CI-1000 (formerly PD141955-2) and CI-972 on a T-cell line MyLa established from a patient with mycosis fungoides. Both PNP inhibitors had significant, dose-dependent, inhibitory effects on the proliferation of the T-cell line. CI-1000 (ED50: 3.7 microM) was approximately six-fold more potent in blocking 3H-thymidine uptake than CI-972 (ED50: 22.5 microM). The inhibitory effect of either substance could not be increased by addition of deoxyguanosine. Flow cytometric analysis revealed that both PNP inhibitors caused a block in the S-phase of the cell cycle. The inhibitory effect on proliferation was reversible partially by addition of IL-2. When testing proliferation inhibition of both substances on an IL-2-dependent T-cell line (SeAx), their inhibitory effects were reduced significantly. These data document a mechanism of action of the PNP inhibitors independent of deoxyguanosine and partially reversible by IL-2. The authors' observations suggest the potential use of PNP inhibitors in the therapy of cutaneous T-cell lymphomas and provide evidence for a pathway independent from deoxyguanosine by which PNP inhibitors might function in T cells.

Cell Cycle↗

Primary subcutaneous leiomyosarcoma exhibiting the characteristic immunophenotype positive for vimentin and desmin.

BACKGROUND: Primary subcutaneous leiomyosarcoma is a rare neoplasm composed of plump, elongated spindle cells arranged in interweaving fascicles. OBJECTIVE: Differential diagnosis might be facilitated by the use of immunohistochemistry. METHODS: A case of subcutaneous leiomyosarcoma was investigated histologically on paraffin-embedded tissue and immunohistochemistry was performed following standard procedures. RESULTS: The case reported exhibited light microscopic features and an immunophenotype characteristic of leiomyosarcoma. However, the intermediate filament desmin could only be found on a small number of tumor cells. CONCLUSION: Expression of these markers might vary considerably and immunoperoxidase stainings need to be carefully evaluated. Utilization of several antibodies directed against different desmin epitopes might be advantageous.

Aged↗

Predominant usage of distinct T-cell receptor V beta regions by epidermotropic T cells in psoriasis.

To investigate the role of T cells in psoriasis, we analyzed the T-cell receptor (TCR) repertoire in peripheral blood lymphocytes (PBLs) and in skin lesions of 9 patients with chronic plaque-stage psoriasis by means of immunohistochemistry. An extended panel of monoclonal antibodies detecting 11 different V beta families was employed in this study. In the peripheral blood, no predominant TCR V beta expression was detected and interindividual differences were small. Skin-infiltrating T cells showed only marginal differences in the TCR V beta usage when compared with PBLs. However, in 3 patients the intraepidermal infiltrate comprised up to 40% of T cells expressing a TCR V beta region which was virtually absent in the peripheral blood and the dermal infiltrate. Thus, although the TCR V beta usage of skin-infiltrating T cells showed little difference compared to PBLs, several cases exhibited a significant increase of epidermotrophic T cells using one particular V beta region.

Epidermis↗

In vitro and in vivo effects of photodynamic therapy in cutaneous T cell lymphoma.

Photodynamic therapy consists of the combination of photosensitizers absorbing light in the visible spectral region and irradiation with light of corresponding wavelengths. We analysed its effects in comparison to PUVA treatment on cell lines MyLA and HuT78, established from patients with cutaneous T cell lymphomas. Proliferation was reduced to 50% by exposure to 7.5 J/cm2 UV-A (= ED50). This effect was increased more than 10-fold in the presence of 10 micrograms/ml 8-methoxypsoralen. The ED50 for photodynamic therapy using 630 nm light emitted by a dye laser and 10 micrograms/ml Photosan-3 was found to be about 1 J/cm2. In vivo fluorescence recordings during topical photodynamic therapy of mycosis fungoides lesions showed photo-bleaching and thus documented the triggering of photochemical reactions. Our observations document the capability of photodynamic therapy to inhibit proliferation of transformed T cells similar to PUVA, pointing out its potential in the treatment of cutaneous T cell lymphomas.

Cell Line↗

Combined immunophenotyping and karyotyping in peripheral T cell lymphomas demonstrating different clonal and nonclonal chromosome aberrations in T helper cells.

Combined immunophenotyping and karyotyping was performed in seven cases of peripheral T cell lymphoma with complex aberrant clones. Various lymphocytic cell populations entered mitosis, whereas all aberrant cells belonged to the T helper/inducer cell population. Lymphomas with the same recurrent chromosome aberrations, i.e. inversion inv(14)(q11q32.1) and isochromosome i(8)(q10), had a very similar immunophenotype. The aberrant cells in these cases expressed CD3+, CD4+, CD7+, CD45RO+. The immunophenotypic similarity is underlined in one case of T prolymphocytic leukemia, in whom the aberrant cells lost the CD8 antigen originally present, during cultivation with PHA. In one case of Sézary's syndrome, two or possibly even three different clones as well as nonclonal aberrations were identified within the T (helper/inducer) cell population, providing further evidence that chromosomal instability is a characteristic feature of cutaneous T cell lymphoma.

Adult↗

Clonal disease in early cutaneous T-cell lymphoma.

Our experience with 185 cases of T-cell dominated skin infiltrates demonstrates that the PCR-based method for detection of TCR gamma chain gene rearrangement in combination with temperature gradient electrophoresis can routinely be used for the demonstration of clonal T cells in formalin-fixed and paraffin-embedded biopsies of lesional skin. In contrast to Southern blot analysis, the amplification by PCR is nonradioactive, is not time consuming (approximately 3 days), can be performed using frozen or paraffin-embedded tissue, and allows additional molecular biologic analyses, such as sequencing. Furthermore, it offers the possibility to design patient-specific primers for monitoring of the disease activity. It also has to be concluded from our study that all available clinical, histologic, cytologic, immunophenotypical, and rearrangement studies have to be considered in order to establish the correct diagnosis.

Blotting, Southern↗

Adhesion molecules in normal human conjunctiva. An immunohistological study using monoclonal antibodies.

In this immunohistochemical light microscopic study we applied a panel of monoclonal antibodies to study the expression pattern of adhesion molecules in normal human conjunctiva from 15 patients. The molecules we analyzed included the VLA-family VLA-1-6, the leukocyte integrins LFA-1, Mac-1 and p150,95, the immunoglobulins LFA-3, CD2, ICAM-1 and VCAM-1 and the selectin ELAM-1. Our results show that only VLA-2, VLA-3, LFA-3, and the VLA-alpha 6 subunit are expressed on the epithelium. A strongly basal accentuation of the VLA-alpha 6 subunit indicates its possible relevance in anchoring the epithelium at the substantia propria. Intraepithelial T cells were VLA-1, VLA-5, LFA-1, and CD2 positive. Endothelial cells expressed VLA-1, VLA-2, VLA-3, VLA-5, VLA-alpha 6, ICAM-1, and LFA-3. ELAM-1 was seen only in specimens from five patients. Interestingly, mast cells were positive for VLA-3 and VLA-5, both of which are receptors for fibronectin, indicating that these integrins play an important role in mast cell function. Our study builds the basis for further investigations in adhesion molecules in conjunctival diseases.

Adolescent↗

A majority of proliferating T cells in cutaneous malignant T cell lymphomas may lack the high affinity IL-2 receptor (CD25).

IL-2 is a major growth factor for all T-cell subsets acting via a specific membrane receptor. To investigate its role in the pathogenesis of cutaneous T-cell lymphomas (CTCLs), we analysed the expression of high-affinity IL-2 receptors (IL-2Rs) on proliferating cells in these disorders. We showed by immunohistochemical double staining that most cycling cells do not express high-affinity IL-2Rs. Four T-cell lines were established from patients with CTCLs. Two lines required both IL-2 and IL-4 for growth, one line required IL-2 and one line IL-4 alone. The last of these lacked expression of the IL-2R alpha-chain. Thus, IL-2 may not be the only, or the most important, growth stimulus in CTCLs and reactive skin infiltrates. T helper cells, which dominated the infiltrate, might represent TH2 cells.

Biomarkers↗

Oligonucleotide typing reveals association of type I psoriasis with the HLA-DRB1*0701/2, -DQA1*0201, -DQB1*0303 extended haplotype.

Although the pathogenesis of psoriasis is still a matter of debate, there are several lines of evidence supporting the concept of this disease being immunologically mediated with T cells playing a crucial role. Because a considerable portion of the cellular infiltrate in psoriasis consists of activated T-helper cells, expression of HLA class II antigens might be of particular importance for the understanding of its pathogenesis. Therefore, we investigated the HLA type of patients with type I (early onset, positive family history) and type II (late onset, no family history) psoriasis by means of serology (n = 89) and genotyping using sequence-specific oligonucleotide probes (n = 64). Serologic analysis of class I documented the association of type I psoriasis with HLA-Cw6, -B13, and -B57, whereas type II psoriasis showed a weaker correlation with HLA-Cw2 and -B27. Genotyping using SSO for class II detected the elevation of the HLA-DRB1*0701/2 allele frequency from 13% in normal population to 36% in type I, but only to 15% in type II psoriatics. Moreover, positive correlations with type I psoriasis were detected for HLA-DQA1*0201 and HLA-DQB1*0303. The HLA-DRB1*0701/2, -DQA1*0201, -DQB1*0303 extended haplotype was found exclusively in type I psoriasis. This is the first report documenting the association of distinct HLA class II alleles with type I psoriasis as detected on the DNA level, an approach both more specific and more sensitive when compared to serology.

Adult↗

Discrimination between immunoaccessory and phagocytic monocytes/macrophages of the skin in paraffin-embedded tissue by the monoclonal antibody Ki-M1P.

The variety of functions performed by monocytes and macrophages is reflected in their phenotypic diversity. Investigation of this complex system is facilitated by Ki-M1P, a new monoclonal antibody which recognizes a differentiation antigen on monocytes/macrophages in paraffin-embedded tissues. To test its usefulness as a pan-macrophage marker in the skin, we immunohistochemically analysed paraffin-embedded biopsy material from seven healthy individuals and 190 patients with a variety of dermatoses. Immunoreactivity was compared with results obtained with the antibodies KP-1, MAC-387, UCHL-1 and S-100. In normal skin, epidermal Langerhans cells were Ki-M1P-. Strong expression of this marker was detected on spindle-shaped as well as dendritic perivascular and intervascular macrophages. Pathological reaction forms such as giant cells and epithelioid cells in granulomatous dermatoses were also Ki-M1P+. The high specificity of Ki-M1P is reflected in the lack of reactivity with tumour cells in non-monocytic neoplasms and Langerhans cell histiocytosis. Thus, Ki-M1P is a useful marker for skin macrophages, discriminating between the immunoaccessory and the phagocytic compartments.

Antibodies, Monoclonal↗

Langerhans cell accumulation in chronic tinea pedis and pityriasis versicolor.

Persistence of chronic tinea pedis (CTP) and pityriasis (tinea) versicolor (PIVE) has been tentatively attributed to an impaired cellular immune response. Therefore immunophenotyping of the inflammatory infiltrates in both disorders was performed in order to detect possible defects in cellular defence. The results of the present study show a dominance of memory T cells, an accumulation of macrophages and lack of B cells. A very prominent feature in CTP and especially PIVE was a marked accumulation of Langerhans cells (LCs) in the epidermis, mostly without expression of CD4. Furthermore, reduced expression of cellular activation markers and the presence of suppressor T cells was noted. In general, the cellular response in PIVE appeared to be slightly stronger than in CTP. This composition of the inflammatory infiltrates in chronic dermatomycoses is similar to previous findings in a variety of dermatoses. However, in PIVE and CTP local reduction of delayed-type hypersensitivity may occur. The function of LCs in these infections is therefore of special interest.

Chronic Disease↗

Cellular and molecular composition of human skin in long-term xenografts on SCID mice.

We report on the immunophenotypical characterization of adult human skin transplanted onto severe combined immunodeficient (SCID) mice. Thirty animals were followed for up to 12 months after receiving split-thickness xenografts, of which 28 were tolerated for the whole test period. Antigen mapping revealed an almost complete preservation of human cellular and extracellular tissue components in long-term transplants including skin immune cells (Langerhans-cells, macrophages, lymphocytes) and also parts of the engrafted endothelium. Hence, xenografts on SCID mice offer a versatile experimental tool for the in vivo study of both human skin immune cell function and endothelial cell-mediated interactions in an environment completely devoid of interferences by adoptive host immune response.

Animals↗