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Biomedical subjects

W Sterry

Publications and source records attributed to W Sterry.

At least 181 records · Page 10Linked to original sources
PubMed1996

IL-7 mRNA is not overexpressed in mycosis fungoides and pleomorphic T-cell lymphoma and is likely to be an autocrine growth factor in vivo.

Interleukin-7 (IL-7) is thought to be a growth factor for cutaneous T-cell lymphoma (CTCL) since it has been shown that IL-7 transgenic mice develop a cutaneous disorder characterized by enhanced T-cell proliferation with progression to malignancy and that in vitro growth of Sézary cell lines is IL-7 dependent. However, no direct in vivo evidence exists for the involvement of IL-7 in the pathogenesis of CTCL. Therefore, we examined IL-7 mRNA expression in skin biopsies from patients with mycosis fungoides (MF) (n = 20) and pleomorphic T-cell lymphoma (n = 5). By semiquantitative RT-PCR, IL-7 mRNA was not detectable in any of the CTCL samples, or in normal human skin (n = 8) or in skin from patients with psoriasis (n = 7) or atopic dermatitis (n = 5). In contrast, IL-7 mRNA was detected in a biopsy from a kidney allograft transplant, in normal keratinocytes under various culture conditions and in several cell lines. Interestingly, using a highly sensitive nested PCR, IL-7 mRNA was detectable in all specimens tested, but there was no indication of IL-7 overexpression in MF then analysing lesions of patch, plaque or tumour stages. In contrast, increasing CD3 expression was found, which was most likely a consequence of the enhanced density of malignant T cells in advanced tumour stages. In summary, by the use of semiquantitative RT-PCR we were not able to detect IL-7 overexpression in MF or pleomorphic T-cell lymphoma. This indicates that IL-7 is probably not an autocrine growth factor in these CTCLs.

Adult↗
PubMed1996

The superantigen exfoliative toxin induces cutaneous lymphocyte-associated antigen expression in peripheral human T lymphocytes.

Several immune-mediated dermatoses including psoriasis and atopic dermatitis can be exacerbated by bacterial infections. Superantigen producing bacteria can be isolated from skin lesions of these dermatoses. Consistent with superantigen effects, skewed T cell receptor variable gene usage has been demonstrated within these lesions. Therefore, the question arises whether superantigen induce a skin-seeking phenotype within peripheral T cells. In this study, we investigated the in vitro influence of the V beta 2-selective superantigen exfoliative toxin from Staphylococcus aureus on the expression of the cutaneous lymphocyte-associated antigen on peripheral T lymphocytes of healthy donors. We demonstrate that exfoliative toxin dramatically upregulates cutaneous lymphocyte-associated antigen expression on T cell receptor V beta 2+ lymphocytes. Up to 69% of V beta 2+ lymphocytes expressed cutaneous lymphocyte-associated antigen after 5 days of in vitro culture. Additionally, exfoliative toxin also increased cutaneous lymphocyte-associated antigen expression in CD3+ T cell receptor V beta 2- lymphocytes indicating a different effect as caused by the superantigen-T cell receptor V beta 2 interaction. Our findings suggest influence of bacterial superantigens on T lymphocyte skin homing in vivo.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1996

The immunology of bullous oculo-muco-cutaneous disorders.

In skin-blistering diseases, alteration of cellular adhesion results in a loss of cohesion of the epithelium of the skin and the mucous membranes. These disorders are often genetically determined and involve highly specific autoantibodies. A recent workshop discussed the immunology of these diseases.

Eye Diseases↗
PubMed1996

Identification of lymph node metastases by use of polymerase chain reaction (PCR) in melanoma patients.

Diagnosis of clinically suspected lymph node metastases in melanoma patients can be confirmed with high sensitivity and specificity by fine needle aspiration (FNA) cytology. However, small lymph nodes or haemorrhagic metastases may yield negative or unevaluable cytology. We tested whether the sensitivity and specificity of presurgical diagnosis could be improved by a polymerase chain reaction (PCR) method, identifying tyrosine-mRNA in samples obtained by fine needle aspiration (FNA-PCR). PCR was positive in 17 of 18 histopathologically proven melanoma metastases, while conventional cytopathology detected 16 of 18. 4 of 9 disease-free melanoma patients with negative FNA cytology had positive PCR results, but controls gave negative results. FNA-PCR analysis cannot be recommended as superior to conventional FNA cytological examination. Whether the positive FNA-PCR in four of the nine clinically unsuspicious regional lymph nodes correlates with earlier disease progression or indicates lower specificity of the method will need further investigation.

Base Sequence↗
PubMed1996

Detection of early micrometastases in subcutaneous fat of primary malignant melanoma patients by identification of tyrosinase-mRNA.

To improve survival following melanoma excision, wide margin resection including subcutaneous fat, is indicated. Subcutaneous fat, resected with primary melanomas, was investigated using the tyrosinase PCR method originally described for detection of melanoma cells in peripheral blood. Identification of tyrosinase transcripts was possible in 4 melanoma patients (3 Clark level IV, 1 level III), while negative results were obtained from 6 other patients (2 level IV, 3 level III and 1 level I). In control experiments, after infiltration of the reference cell line SkMel into normal fat tissue, the PCR was positive in 33% (3/9) with 10(2) infiltrated cells, 69% (9/13) with 10(4) cells and in 100% (7/7) with 10(6) cells. We conclude that detection of melanoma cells in subcutaneous fat tissue is possible by tyrosinase PCR. Follow-up studies should show whether such positive tyrosinase PCR can define patients at very high risk of tumour relapse.

Adipose Tissue↗
PubMed1996

A phase II study of dacarbazine, cisplatin, interferon-alpha and high-dose interleukin-2 in 'poor-risk' metastatic melanoma.

Melanoma patients with very advanced disease have usually not been included in chemo-immunotherapy trials. We report on 22 melanoma patients, including 5 with reduced performance status (Karnofsky PS < 70), 8 with metastatic ocular melanoma, 6 with brain metastases, and 4 who had pretreatment with interleukin-2. These were treated with a combination regimen of dacarbazine (250 mg/m2, days 1-3), cisplatin (30 mg/m2, days 1-3), interferon-alpha 2a (IFN-alpha, 10 Mio IU/m2 s.c., days 1-5) and IL-2 (i.v., 18 Mio IU/m2 for 6, 12, 24 h, followed by 13.5 Mio IU/m2 in 72 h). In the case of brain metastases radiotherapy was added. No grade IV toxicity occurred and no dose reductions were necessary. 21 patients were evaluable for response. 6 (29%) had disease progression, 5 (24%) had partial response and 10 (48%), had stable disease. Sites of response included skin, lymph nodes, muscle, lung, pleura, liver, pancreas, adrenal gland and brain. The described treatment schedule is safe and active even in patients with metastatic melanoma and poor prognosis.

Adult↗
PubMed1996

Allergy to the heat-labile proteins alpha-lactalbumin and beta-lactoglobulin in mare's milk.

BACKGROUND: Allergy to mare's milk is rare. Recently, however, mare's milk has been recommended for treatment of various ailments by practitioners of "alternative medicine," and it is available in health food stores. OBJECTIVE: We report a case of allergic reaction to mare's milk in a 51-year-old woman who was able to tolerate cow's milk. METHODS: The protein composition of mare's milk was determined by methods based on measurement of nitrogen content. The patient underwent prick and intracutaneous tests with commercially available bovine milk proteins and several mare's milk preparations, including mare's milk granulate and boiled mare's milk. RAST and immunoblotting were also performed. RESULTS: Results of skin testing and RAST with cow's milk were negative but demonstrated an IgE-mediated allergy to mare's milk. Immunoblotting revealed two allergen bands with molecular weights of 16 and 18 kd, most likely representing the whey proteins alpha-lactalbumin and beta-lactoglobulin. The bands disappeared after the mare's milk was boiled, indicating that the proteins are heat-labile. CONCLUSION: The results of this study demonstrate the existence of an IgE-mediated mare's milk allergy caused by low molecular weight heat-labile proteins, most likely alpha-lactalbumin and beta-lactoglobulin, which do not cross-react with the corresponding whey proteins in cow's milk.

Allergens↗
PubMed1996

Progression of mycosis fungoides is associated with increasing cutaneous expression of interleukin-10 mRNA.

Cytokines are believed to play an important role in the pathogenesis of cutaneous T cell lymphoma. Data regarding the local cytokine pattern in mycosis fungoides (MF) are partly conflicting. Recent studies have suggested a shift from type 1 to type 2 cytokine pattern because IL-4 and IL-5 mRNA have been more frequently detected in lesions of advanced stages. Another study has described a type 1 cytokine pattern in MF lesions. None of the previous studies of cytokine mRNA expression in MF, however, used quantitative methods, and therefore only the presence of a cytokine, but not the level of expression, could be determined. To gain better insight into the development of cytokine pattern during tumor progression we used semiquantitative reverse transcriptase-polymerase chain reaction to analyze cytokine mRNA expression in MF skin lesions at different stages. Biopsies from patients with patch (n = 11), plaque (n = 6), and tumor (n = 3) stage MF were compared with biopsies from patients with pleomorphic T cell lymphoma (n = 5), psoriasis (n = 7), atopic dermatitis (n = 5), and nonlesional skin (n = 8). MF progression was associated with significantly higher IL-10 and lower interferon-gamma mRNA expression. Moreover, the stage-dependent increase in IL-10 mRNA expression was also found in paired samples from individual patients. Unlike in pleomorphic T cell lymphoma, however, typical T helper 2 cells did not seem to be the source of increasing IL-10 in advanced MF, because stage-independent IL-4 mRNA was rarely detected, suggesting contribution of nonlymphoid cells to local IL-10 production. The overexpression of IL-10 in MF may be of importance for tumor progression, because this immunosuppressive cytokine might be involved in downregulation of immunologic tumor surveillance.

Disease Progression↗
PubMed1996

Familial juvenile onset psoriasis is associated with the human leukocyte antigen (HLA) class I side of the extended haplotype Cw6-B57-DRB1*0701-DQA1*0201-DQB1*0303: a population- and family-based study.

To further evaluate the nature of the HLA association with psoriasis, HLA haplotypes of 60 patients with type 1 (early onset, positive family history) and 30 patients with type II (late onset, no family history) psoriasis were investigated by polymerase chain reaction sequence-specific oligonucleotide hybridization (HLA class II) and serology (HLA class I). Ethnically matched blood donors (146) served as controls. In type I, but not type II psoriasis, the Caucasian HLA extended haplotype (EH) Cw6-B57-DRB1*0701-DQA1*0201-DQB1*0303 named according to the B allele EH-57.1 was highly significantly overrepresented (p cor= 0.00021). This particular EH was present in 35% of type I psoriatics but only 2% of controls. EH-57.1+ individuals therefore carry a 26 times higher risk of developing type I psoriasis than individuals who are EH-57.1-negative Further analysis of individual HLA alleles revealed that within EH-57.1, HLA class I antigens (Cw6-B57) were associated to a much higher extent with type I psoriasis than the HLA class II alleles (DRB1*0701-DQA1*0201-DQB1* 0303). Pedigree analysis of three multiply affected families over three generations revealed a cosegregation of disease with EH-57.1. These results strongly suggest that a gene for familial psoriasis is associated with the class I side of the extended haplotype Cw6-B57-DRB1*0701-DQA1*0201-DQB1*0303.

Base Sequence↗
PubMed1996

[Prerequisites for effective therapy of chronic recurrent vaginal candidiasis].

67 women with chronic recurrent or persistent vaginal candidosis between 5-79 years of age were seen in our outdoor department. In 34 cases, yeasts could be isolated in a vaginal swab taken at the first consultation. On average the patients reported 5 episodes per year during the last years. Typical symptoms consisted of pruritus vulvae, local inflammation and a curdy vaginal discharge. Nearly all of the women had received local or systemic antimycotic treatment for several times. In 53% (18 patients), C. albicans had been isolated, in 29% (10 patients) C. glabrata and in 9% (3 patients) C. krusei. While candidosis due to C. albicans and C. krusei was frequently associated with distressing complaints, infections with C. glabrata caused only very few symptoms. Independent of the species, severe and persistent infections were characterized by long term persisting specific IgM-antibody-titers and remarkable lack of IgG-antibodies. The laboratory parameters of WBC, CRP and immunelectrophoresis were normal. The minimum inhibitory concentrations (MIC) of 60 Candida strains against fluconacole were determined by microdilution assay. The MIC for C. albicans (n = 35) were between 0.78 and 3.125 micrograms/ml, for C. glabrata (n = 20) between 8 and 32 micrograms/ml and for C. krusei (n = 5) between 25 and 128 micrograms/ml. In 7 cases, local antimycotic treatment was sufficient. Correlating to the sensitivity, 18 women were treated with 100-800 mg fluconacole/d for 10-20 days. In 13 of them, clearance of symptoms and yeasts was achieved. The treatment of fluconacole-resistant strains with itraconazole (100-200 ml/d for 10-20 days) together with local application of nystatin (2 x 1 Mio. IE for 10 days) was without any effect. Three women with C. albicans, C. glabrata and C. krusei infection received a candidin-vaccination (0.005 BE/ml-500 BE/ml). In all of these cases, production of IgM-antibodies was induced. However, the clinical symptoms could not be influenced. Only in two cases it was not possible to reach a clearance of symptoms and yeasts. The results show the benefit of a precise differentiation before therapy. Serologic controls of antibody titers seem to be useful tools to control the efficacy of treatment.

Adolescent↗
PubMed1996

T-cell receptor beta variable region (V beta) usage in cutaneous T-cell lymphomas (CTCL) in comparison to normal and eczematous skin.

Cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of lymphoproliferative disorders. We investigated the variable region (V beta) of the T-cell receptor (TCR) repertoire in CTCL and compared it to the V beta repertoire in normal and eczematous skin. We used a panel of 21 anti-V beta antibodies and investigated 84 biopsies of 71 CTCL patients (4 parapsoriasis en grandes plaques (PA), 1 lymphomatoid papulosis, 29 mycosis fungoides (MF), 13 Sezary syndrome (SS), 1 CD8+ CTCL, 11 pleomorphic CTCL (PLEO), 12 CTCL nor classified). Six biopsies of normal skin and 6 of eczematous skin lesions served as controls. We determined the frequency of the V beta in normal and inflamed skin and compared it to the percentage of the respective V beta in the malignant clone of the CTCL patients. The percentage of the V beta positive CD4+ cells in relation to the total number of T cells in normal skin and inflamed skin differed from the distribution of the V beta families in the peripheral blood mononuclear cells (PBMC). Out of 71 CTCL cases, the clone was identified in 23 (32%). We identified the following clones: 1 V beta 3.1 (16MF), 7 V beta 5.1 (1 CD8+ CTCL, 1 CTCL not classified, 1 MF, 1 PA, 3 SS), 1 V beta 6.7 (1 SS), 7 V beta 8.1/8.2 (2 CTCL not classified, 1 PLEO, 2 MF, 2 SS), 1 V beta 12.1 (1 PLEO), 3 V beta 17.1 (2 CTCL not classified, 1 MF), 2 V beta 22.1 (1 CTCL not classified, 1 MF), 1 TCR delta (SS). The frequency of the malignant clone V beta usage corresponded well to the repertoire of V beta in eczematous skin but not to the repertoire in PBMC. In 6 patients, the malignant clone was mainly localized in the epidermis. In 17 cases, the clone-specific cells were distributed in epidermis and dermis equally. A retrospective analysis showed that preferential epidermal homing of the clone was associated with a non-aggressive clinical course. The V beta usage of CTCL and eczema suggests a special cutaneous microenvironment which might be co-created by certain (bacterial?) superantigens. A preferential epidermal homing of the clone might have prognostic implications.

Adolescent↗
PubMed1996

Integrity of the permeability barrier regulates epidermal Langerhans cell density.

Previous studies have shown that barrier requirements regulate epidermal liquid and DNA synthesis. In the present study, we examined the possibility that the integrity of the permeability barrier influences epidermal Langerhans cells involved with the immune response. Barrier disruption was achieved by treatment of human skin with acetone, sodium dodecylsulphate (SDS), or tape stripping, until a 10-20-fold increase in transepidermal water loss was achieved. Serial biopsies were performed 6-168 h after treatment, and Langerhans cells were complexed with anti-CD1a (Leu6) or S-100 antibodies, and visualized with an immunoperoxidase technique. Acetone treatment resulted in an increase in epidermal Langerhans cell density, reaching a maximum of 94% over control (P < 0.01) by 24 and 48 h post-treatment. Following SDS treatment or tape stripping, epidermal Langerhans cell density was increased by 100 and 175% (P < 0.01), respectively. There was a linear correlation between the degree of barrier disruption and the increase in epidermal Langerhans cell density. Studies with the Ki-S3 proliferation-associated nuclear antigen revealed a two- to threefold increase in epidermal proliferation after barrier disruption. The time curves of the increase in Langerhans cell density and the increase in epidermal proliferation were similar, suggesting that there was a coordinate regulation. In contrast with our previous studies employing patch test reactions to allergens or irritants, disruption of barrier function neither resulted in an increased dermal Langerhans cell density, nor influenced T lymphocytes (CD3+, Leu4+), macrophages (KiM8+), ICAM-1 or ELAM-1 expression in the skin. In addition, barrier disruption did not result in either dermal inflammation or epidermal spongiosis. In summary, these findings support our hypothesis that the permeability barrier influences epidermal Langerhans cell density, which is involved in maintaining an immunological barrier.

Acetone↗
PubMed1996

Immunohistochemical localization of cytokines and receptor-associated molecules in human tonsils and skin.

Human tonsilla palatina and skin were investigated by means of light microscopical and electron microscopical immunohistochemistry using monoclonal antibodies (Mab) against some cytokines. In both tonsils and skin we found intracellular immunoreactivity for interleukin-1-beta in macrophages and interdigitating cells. Also some, but not all crypt-epithelial cells were positive, while keratinocytes in the skin were negative. Interleukin-2-immunoreactivity was found in a subpopulation of lymphocytes (probably T-cells) and unexpectedly also in some antigen-presenting cells (APCs). A Mab against interleukin-4 revealed weak labelling of lymphatic cells in the T-cell area of tonsils. The human skin was negative. A Mab that recognizes a molecule associated with the interleukin-4-receptor gave strong surface labelling in tonsils and skin on APCs and weak immunoreactivity on lymphoid cells. Frequently these APCs formed rosettes with weakly labeled lymphocytes. Mabs against interleukin-8 stained starry sky macrophages in the germinal centers of the tonsil and different APCs in the T-cell region. IL-8 is stored in keratinocytes of normal skin, but becomes mobilized under inflammatory conditions. Our results expand the understanding of cell cell-interactions under normal and inflammatory conditions in tonsil and skin.

Antibodies, Monoclonal↗
PubMed1995

[Calciphylaxis].

HISTORY AND CLINICAL FINDINGS: Acute, zigzag-shaped livid skin markings developed on both thighs of a 55-year-old woman who had been on dialysis for 6 years. Within 7 days these areas increased in size to about 10 cm in diameter and contained central dry and painful necroses. On legs, lower arms and hands hard subcutaneous nodules were palpable with a diameter up to 3 mm. For many years the phosphate and parathormone levels, as well as alkaline phosphatase activity had been raised. The patient had often failed to follow treatment recommendations. TESTS: There were increased serum concentrations of calcium (2.8 mmol/l) and phosphate (1.78 mmol/l). The calcium phosphate ion product was 4.98 (mmol/l)2. Furthermore, there were raised levels of alkaline phosphatase (315 U/l) and parathormone (1076 ng/l, normal: 10-65). X-ray film of the hands showed soft tissue and arterial calcifications, while histological examination of a deep skin biopsy revealed calcium phosphate emboli of the main vessels. TREATMENT AND COURSE: Excision of the cutaneous necroses was followed by parathyroidectomy at which only three parathyroid glands were identified and removed. The parathormone level fell postoperatively, but rose again after 4 weeks. The fourth parathyroid gland was then found and removed, after which the parathormone level fell below measurable levels. The skin ulcers healed completely 4 weeks after the second operation.

Calciphylaxis↗
PubMed1995

Shedding of the soluble form of CD30 from the Hodgkin-analogous cell line L540 is strongly inhibited by a new CD30-specific antibody (Ki-4).

The CD30-activation marker was detected as the Hodgkin-associated Ki-I antigen and is regarded as a target for the treatment of Hodgkin patients with immunotoxins. The CD30 is released from tumor cells and this soluble CD30 (sCD30) is an indicator of the disease activity. Since the shedding of sCD30 may be influenced by antibodies, we produced 6 new CD30-specific antibodies (Ki-2 to Ki-7) for the purpose of finding antibodies that might inhibit the formation of sCD30. Ki-2 to Ki-7 and the other anti-CD30 antibodies Ki-I, Ber-H2, HeFi-I, M44, M67, HRS-I, HRS-4 and C10 were employed for epitope mapping. The binding of a particular radio-labeled anti-CD30 antibody to Hodgkin's-disease-derived L540 cells was completed by addition of the various non-labeled anti-CD30 antibodies. Three non-overlapping regions, expressing different antigen-specific determinants, could be defined on the extracellular part of the CD30 molecule. Cluster A of determinants was recognized by Ki-2, Ki-4, Ki-6 and Ki-7, Ber-H2, HRS-I and HRS-4, while cluster B was detected by Ki-I, Ki-5 and M67. Cluster C, which probably contains the binding site for the CD30 ligand, was defined by Ki-3, M44, HeFi-I and C10. Co-culture experiments of L540 cells with the various antibodies followed by the isolation of sCD30 from culture supernatant fluids revealed that the release of sCD30 was most strongly increased by Ki-I and weakly enhanced by Ki-2, Ki-3, Ki-5 and HeFi-I, whereas it was almost completely inhibited by Ki-4 and to a slightly lesser extent by Ber-H2.

Animals↗
PubMed1995

Use of polymerase chain reaction in the detection of clones in lymphoproliferative diseases of the skin.

Early-stage mycosis fungoides shows similar clinical symptoms and histological and immunophenotypical features to several benign lymphoproliferative skin disorders. We analyzed T cell receptor gamma gene rearrangement by polymerase chain reaction in the search for monoclonal lymphoid subpopulations in skin infiltrates. Totally, 283 skin biopsies (paraffin-embedded and frozen material) from patients with different malignant and reactive skin diseases were investigated. Using primers for the T cell receptor gamma chain gene, monoclonality was detected in 59 out of 66 (89%) cases of pleomorphic cutaneous lymphoma, in 60 out of 78 (77%) patients with mycosis fungoides, in 11 out of 22 (50%) cases of parapsoriasis en plaques, in five out of 35 (14%) cases of pseudolymphoma, in six out of 15 (40%) patients with lymphomatoid papulosis, and in none out of 64 patients with inflammatory skin diseases. The results show that clonal T cell population can be detected in the majority of patients with cutaneous T cell lymphoma, but the findings have to be correlated with the histological and morphological features.

Clone Cells↗
PubMed1995

Systemic treatment for cutaneous lymphomas.

Primary malignant T cell lymphomas of the skin form a heterogenous group. Relevant classifications were recently made to separate different entities by various criteria. This is of great importance, because one should only rely on those therapeutical trials in which patients were included according such classifications. In this paper, we will mainly focus on therapeutic modalities for mycosis fungoides, which is the most frequent cutaneous T cell lymphoma and which may serve as a model disease. In principle, local (e.g., psoralens and ultraviolet A, PUVA) and systemic therapies (e.g., interferon-alpha 2a) can be applied. Very recently, we were able to demonstrate that even in initial stages of mycosis fungoides, the T cell clone is not restricted to the skin, but rather is present in low amounts in the peripheral blood. Therefore, systemic therapeutic modalities alone or in combination with local strategies (interferon-alpha 2a and acitretin/PUVA and interferon-alpha 2a) should be more effective, which will be proven by currently running clinical trials.

Antineoplastic Agents↗