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Biomedical subjects

W Sterry

Publications and source records attributed to W Sterry.

At least 199 records · Page 11Linked to original sources

[Modern molecular biology diagnosis of malignant cutaneous lymphomas].

The diagnosis of cutaneous malignant lymphoma is based on clinical, histo-morphological and immunochemical findings and, now a days, on molecular biology analyses of the genotype in the lymphocytic infiltrate. By using the polymerase chain reaction (PCR) with specific primers for the Ig heavy chain gene and the T-cell receptor gamma chain gene, the detection of monoclonal cell populations in the skin infiltrate is possible. Since this method produces results within 3 days, since paraffin-embedded skin and lymph node biopsies and heparinized peripheral blood can be used and since no radioactivity is necessary, this technique has important advantages over traditional techniques such as Southern blot analyses. In addition, specific PCR analyses may allow a patient-specific monitoring during therapy and also may detect early relapses of the lymphoproliferative malignant disease.

Biopsy↗

[Reticular elastolytic giant cell granuloma. A variant of the annular elastolytic giant cell granuloma].

The case report presented describes a new variant of annular elastolytic giant cell granuloma. Over a period of 10 years, a 40-year-old woman had developed reticular, brown to livid, partly atrophic skin lesions on the shoulders and decolletée. The patient had no subjective symptoms. Histology revealed a patchy lymphohistiocytic infiltrate in the dermis, with many giant cells. Elastic fibres were less frequently found in these infiltrates; in a few of the giant cells and macrophages fragments of elastic fibres were demonstrated within the cytoplasm. There were no deposits of mucin. For this new variant we propose the term "reticular elastolytic giant cell granuloma."

Adult↗

[The diagnostic value of antinuclear antibodies].

In this review we focus on the diagnostic importance of antinuclear antibodies (ANA), the biological function of the relevant autoantigens and on some methodological questions regarding the detection of ANA. The qualitative and quantitative evaluation of ANA has improved significantly in recent years with the introduction of several new test kits. A precondition for the rational use of those assays is knowledge of the diagnostic validity of the detected ANA with regard to the method used. ANA are autoantibodies that react with nucleic acids, protein-nucleic acid complexes and proteins of nuclei. The reasons for their in vivo production are unknown. ANA characterize several of the so-called connective tissue autoimmune diseases and their subtypes, either alone or in typical combinations. They differ significantly with regard to their prevalence and thus in their diagnostic validity. Specificity and prevalence do not correlate. ANA are not markers of disease activity except for antibodies against dsDNA. ANA levels can be interpreted correctly only in connection with clinical symptoms and other laboratory findings.

Antibodies, Antinuclear↗

[Dermatomyositis-like skin changes with long-term hydroxyurea (Litalir) therapy].

We report on dermatomyositis-like adverse cutaneous reactions following long-term maintenance therapy with hydroxyurea in two patients suffering from chronic myelogenous leukaemia (CML). In addition to non-specific side effects, such as xerosis, pruritus and hyperpigmentation, both patients presented with more specific skin changes, i.e. erythematous lesions, scaling, and partially atrophic areas distributed in a linear fashion on the dorsal aspects of the hands and fingers. In addition, teleangiectatic erythema of the face was present in both patients, and this was associated with oedema of the eyelids in one patient. Despite these dermatomyositis-like features there were no clinical signs of muscular involvement, and muscle-specific enzymes were within normal ranges. Skin biopsy specimens revealed an interface dermatitis characterized by a lichenoid cell infiltrate, vacuolar alteration of basal cells, necrotic keratinocytes within the spinous zone, focal hypergranulosis, ortho-hyperkeratosis and telangiectases in the upper part of the dermis. Analogous histopathological findings have been documented in lichen planus-like skin changes on the hands following hydroxyurea therapy. It seems doubtful whether there are actually any major differences between those skin changes described as dermatomyositis-like and those interpreted as lichen planus-like in patients receiving long-term hydroxyurea therapy.

Aged↗

Amelanotic lentigo maligna melanoma.

Only five cases of the amelanotic variant of lentigo maligna melanoma of the face have been reported. We describe an additional four patients observed within the past 5 years, suggesting a much higher incidence of this variant than previously suspected.

Aged↗

A subset of macrophages located along the basement membrane ("lining cells") is a characteristic histopathological feature of psoriasis.

In this paper, we describe the immunophenotype and ultrastructure of a new macrophage subpopulation present in inflamed but not in normal human skin. In biopsy material from patients with psoriasis (n = 4), atopic dermatitis (n = 4), and positive patch test reactions (n = 4), spindle-shaped macrophages located along the basement membrane were detected staining positive for CD11c (LeuM5 high, Ki-M1 low), CD68 (Ki-M6 low), and Ki-M8 (low). This subpopulation was most prominent in psoriasis, where a median of 34 macrophages neighbored 100 basal keratinocytes, thus covering about 80% of the dermoepidermal junction. The numbers of atopic and positive patch test reactions were 11 and 13, respectively, accounting for about 20% of the dermoepidermal junction. Transmission electron microscopy revealed an electron-lucent nucleus with dense deposits of chromatin along the nuclear membrane. Interruptions of the integrity of the basement membrane neighboring these cells were also seen. We repeatedly observed parts of basal keratinocytes merging through these openings and macrophages exhibiting cytoplasmic extentions directed toward the porus. Our observations suggest vigorous interactions between macrophages and basal keratinocytes and support the hypothesis that these interactions are an important regulatory event in the pathogenesis of psoriasis.

Antigens, CD↗

Very low monocytic HLA-DR expression indicates high risk of infection--immunomonitoring for patients after neurosurgery and patients during high dose steroid therapy.

In patients with disturbed immunoreactivity caused by trauma or immunosuppressive therapy infections are still a severe problem. To determine whether measurement of monocytic HLA-DR expression is useful for identifying patients with a high risk of infection after elective neurosurgery, blood was obtained from 57 patients during the first 3 days after surgery. HLA-DR expression was lower in 14 patients who developed infection, compared with patients with an uncomplicated postoperative course (p < 0.0001). Out of ten patients with less than 30% HLA-DR positive monocytes, nine developed infection. In 11 neurosurgical patients additional investigations were performed. Measurements in these patients show that HLA-DR expression decreased temporarily within hours after surgery, coinciding with a considerable increase of inflammatory cytokines in CSF, but, surprisingly, not in plasma. High plasma concentrations of ACTH and cortisol hours after surgery indicated a hypothalamus-pituitary axis response, probably involved in the downregulation of monocytic HLA-DR expression. Likewise, monitoring of dermatological patients (n = 10) who received high dose systemic steroids revealed a very low HLA-DR expression in those patients who later developed infection. Our studies show that very low HLA-DR expression indicates high risk of infection. We recommend the measurement of this parameter for immunomonitoring.

Adult↗

T-cell-receptor repertoire in chronic plaque-stage psoriasis is restricted and lacks enrichment of superantigen-associated V beta regions.

Preferential usage of certain T-cell receptors by the lymphocytic infiltrate in psoriasis might indicate the involvement of an antigen in the pathogenesis of this disease. However, to date there are no data on the complete T-cell-receptor V alpha and V beta repertoire in psoriatic patients. We therefore compared the usage of T-cell-receptor variable regions in blood and skin of 10 patients with chronic plaque-stage psoriasis by means of semiquantitative polymerase chain reaction. Additionally, HLA class II alleles were analyzed by means of sequence-specific oligonucleotide typing. A considerable restriction of the T-cell-receptor repertoire was observed in the skin, where up to 20% of the variable regions present in the blood were not detectable. This was true for both alpha- and beta-chains. However, no interindividually constant pattern of T-cell-receptor restriction was deducible. Inconsistently, a certain preferential usage of some beta chains occurred within the cutaneous compartment. This report on the complete T-cell-receptor V alpha and V beta repertoire in psoriasis documents the restricted receptor repertoire of infiltrating T cells and a lack of enrichment of superantigen-associated V beta regions. Thus superantigens seem not to play a pathogenetically relevant role in chronic plaque-stage psoriasis.

Genetic Heterogeneity↗

Differential expression of heat shock protein 70 (HSP70) and heat shock cognate protein 70 (HSC70) in human epidermis.

Autoimmunity and microbial agents have been suggested as playing a pathogenetic role in psoriasis. Since immune responses to microbial infections are often directed towards heat shock proteins (HSP), we investigated the expression of three HSP families in normal and inflamed human skin. Specimens from ten patients with psoriasis and three patients with positive patch tests for nickel and from five healthy volunteers were analysed by means of immunohistochemistry. The patterns observed were qualitatively similar in these conditions showing only minor quantitative differences. Psoriatic epidermis exhibited the highest level of expression. HSP27, HSP70 and heat shock cognate protein 70 (HSC70) were readily detectable. HSP27 was homogeneously distributed throughout the epidermis, whereas HSP70 was restricted to the basal layer and HSC70 primarily to the suprabasal layers. Other HSPs were detected to a lesser degree and showed a more irregular pattern. Thus, the qualitative expression pattern of HSPs seems to be constant between different skin conditions, but the expression of constitutive and inducible HSP70 depends on the differentiation state of keratinocytes.

Blotting, Western↗

In vivo targeting of integrin receptors in human skin xenografts by intravenously applied antibodies.

We examined whether systemically injected monoclonal antibodies (mAbs) directed to cell-surface glycoproteins of human keratinocytes reach their target antigens in xenograft transplants of normal human skin on SCID mice. The integrins alpha 6 beta 4, expressed in the basal cell layer of human epidermis, and glycoprotein T16 (gp 40/50), expressed in terminally differentiating keratinocytes of the stratum spinosum, were selected as targets. It was found that all injected mAbs selectively localized to their antigens and bound and saturated their targets even in the uppermost layers of the stratum malpighii. This could easily be monitored by direct immunofluorescence staining since SCID mice lack endogenous production of significant amounts of immunoglobulins. After a single injection, mAbs could still be detected at the target site after 14 days. Our results proved that heterologous immunoglobulins pass systemic capillary filters in this xenograft model and specifically bind to their target molecules. Thus, xenografted SCID mice provide a versatile model for studying cell-surface glycoprotein-mediated interactions by the use of functionally interfering antibodies under in vivo conditions in human skin.

Animals↗

Photodynamic therapy in psoriasis: suppression of cytokine production in vitro and recording of fluorescence modification during treatment in vivo.

Photodynamic therapy (PDT) consists of the combination of photosensitizers absorbing light mainly in the red spectral region and irradiation with light of corresponding wavelengths. We analysed its effects on the cytokine secretion (IL-1 beta, TNF alpha, IL-6) of freshly isolated peripheral mononuclear cells from six patients with chronic plaque-stage psoriasis in comparison with PUVA. PUVA treatment resulted in a decreased production of all three cytokines, but most pronounced in the case of IL-6. PDT caused a similar change in the cytokine pattern, but its effectiveness was lower. In vivo fluorescence recordings were performed on psoriatic plaque lesions after topical application of the photosensitizer Photosan-3. Under irradiation, progressive photobleaching was noted with increasing radiation dosage. This is the first reported study of photochemical reactions using on-line fluorescence recordings during PDT of psoriatic lesions in vivo. Our results demonstrate the capacity of PDT to cause immunomodulatory effects similar to PUVA, thus indicating its potential application to the treatment of this common disease.

Cytokines↗

Psoriasiform architecture of murine epidermis overlying human psoriatic dermis transplanted onto SCID mice.

Preliminary observations in a xenogeneic SCID mouse transplantation model indicated that murine epidermis overgrows human dermis from psoriatic skin but not that form normal skin. To investigate the effect of peripheral blood mononuclear cells on the differentiation of murine keratinocytes, we transplanted involved and uninvolved full-thickness skin from patients with psoriasis onto SCID mice and followed this with repeated subcutaneous injections of cells suspended in patient serum. After 6 weeks grafts were analysed morphologically and immunohistochemically. The epidermis in grafts from clinically uninvolved skin appeared normal. The persistence of a psoriasiform epidermis was noted in all grafts from affected sites despite a lack of lymphocytic infiltration. Staining for human and mouse MHC class I antigens revealed the murine origin of keratinocytes forming the psoriasiform epidermis, while the human dermis was retained. Our observations indicate that the defect underlying the pathogenesis of psoriasis is most likely located in the dermal rather than the epidermal compartment. This xenogeneic transplantation model may be useful for future studies of the pathogenesis and treatment of psoriasis.

Animals↗

[Anticonvulsant hypersensitivity syndrome to carbamazepine].

In a 39-year-old woman an anticonvulsant therapy was initiated because of focal attacks in the left arm and face. The patient experienced generalized maculopapular skin rashes in response to each of four chemically similar anticonvulsant drugs: phenytoin, carbamazepine, primidone and clonazepam. During administration of carbamazepine the clinical features included fever, hepatitis and hematological eosinophilia in addition to the skin rash (anticonvulsant hypersensitivity syndrome). The anticonvulsant hypersensitivity syndrome is defined as an idiosyncratic reaction caused by disturbed drug metabolism. Positive lymphocyte-transformation tests with carbamazepine and phenytoin indicate an immunological mechanism underlying the rashes in our patient. Patch testing with the four anticonvulsant drugs gave positive results only with carbamazepine. Skin biopsy showed the histological features of a delayed-type allergy. The anticonvulsant therapy was continued with a chemically unrelated preparation, valproic acid; this drug is well tolerated and has proved appropriate for prevention of seizures.

Adult↗