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Biomedical subjects

W Sterry

Publications and source records attributed to W Sterry.

At least 127 records · Page 7Linked to original sources
PubMed1999

Interleukin 10 treatment of psoriasis: clinical results of a phase 2 trial.

OBJECTIVE: To determine the safety and clinical effects of interleukin 10 (IL-10) treatment of psoriasis. DESIGN AND METHODS: In an open-label phase 2 trial, 10 patients with psoriasis subcutaneously received recombinant human IL-10 over a 7-week period in a dosage of 8 microg/kg daily (n=5) or 20 microg/kg 3 times per week (n=5). Patients were followed up for an additional 5 weeks. RESULTS: The treatment was well tolerated. Antipsoriatic effects were found in all but 1 patient. A significant decrease of the psoriasis area and severity index by 55.3% +/- 11.5% (mean +/- SEM) was observed (P<.02). The antipsoriatic efficiency was confirmed by histological examination. Heterogeneity in the effectiveness was found among the patients, but seems to be independent of the dosage regimen. However, a tendency to a better response was found in the patients who received 20-microg/kg IL-10 3 times per week. Decreasing response in the delayed-type hypersensitivity reaction against recall antigens indicated immunosuppressive effects. Moderate effects on hematopoietic cells were observed. CONCLUSIONS: Our data suggest that IL-10 therapy for psoriasis is safe and possibly clinically effective. Consequently, its value in psoriasis and similar immune diseases should be further determined. Dose-finding, placebo-controlled, double-blind trials are necessary now.

Adult↗
PubMed1999

Analysis of V(H)-D-J(H) gene transcripts in B cells infiltrating the salivary glands and lymph node tissues of patients with Sjögren's syndrome.

OBJECTIVE: In patients with Sjögren's syndrome (SS), B lymphocytes have been found to infiltrate salivary glands, resulting in sialadenitis and keratoconjunctivitis. The disease is frequently associated with benign and neoplastic lymphoproliferation. The present study was undertaken to investigate whether clonal B cell expansion takes place in lymphocytic infiltrations of salivary glands under (auto- [?]) antigen stimulation, by analyzing in more detail the variable part (V(H)-D-J(H)) of the immunoglobulin heavy chain genes expressed in these B cells. METHODS: Biopsies of the labial salivary glands and lymph nodes were performed on 2 female patients with SS. The Ig gene rearrangements in these tissues were amplified by reverse transcriptase-polymerase chain reaction using specific primers. RESULTS: A total of 94 V(H)-D-J(H) transcripts were cloned and sequenced. Our data suggest a polyclonal origin of the B cell infiltrates. In 92 of the transcripts, V(H) genes were modified by somatic mutation. Further analysis showed counterselection for replacement mutations within the framework regions, suggesting that those B cells were stimulated and selected for functional expression of a surface Ig. In labial salivary glands from both patients, clonally related B cells became evident. Members of 1 particular clone were found in both the lip and lymph node material. CONCLUSION: These data provide evidence, on the nucleotide sequence level, that an antigen-triggered clonal B cell expansion takes place in the salivary glands of patients with SS who do not have histologic evidence of developing lymphoma. It may be speculated that those B cell clones expand during disease progression, resulting in lymphomagenesis.

Amino Acid Sequence↗
PubMed1999

[Interleukin-10 in dermatology].

In recent years the investigation of cytokines has been a focus of scientific interest in order to understand the pathogenesis of a variety of diseases. In additions cytokines are increasingly being used for therapeutic purposes, including dermatologic disorders. IL-10 is a recently described cytokine with anti-inflammatory and immunosuppressive qualities which plays an important role in immunoregulation. The overexpression of this mediator has been proven in some inflammatory dermatoses as well as in various skin tumors. These observations help to understand down regulatory events in hyper-inflammatory conditions such as allergic or toxic dermatitis on the one hand and the suppression of an adequate anti-tumor response and thereby the progression of malignant tumors on the other hand. Recent investigations indicate a relative IL-10 deficiency in psoriasis. Initial therapeutic applications of IL-10 in psoriasis underline the pathophysiological importance of this cytokine.

Humans↗
PubMed1999

Interleukin-10 in cutaneous disorders: implications for its pathophysiological importance and therapeutic use.

With its antiinflammatory and immunosuppressive properties interleukin-10 (IL-10) plays a dominant role in several immune reactions including regulatory mechanisms in the skin. The overexpression of this mediator has been reported in some inflammatory dermatoses as well as in various skin tumors. These observations are of importance since they may explain the limitation of hyperinflammatory conditions as in eczemas and erythemas on the one hand and the suppression of an adequate antitumor response and thereby the progression of malignant tumors on the other hand. Moreover, elevated IL-10 expression might contribute to an enhanced risk of development of microbacterial superinfections, a frequent finding in several dermatoses, and might also be involved in the pathogenesis of connective tissue diseases. In contrast, recent studies indicate a relative IL-10 deficiency in psoriasis. Early clinical data from psoriatic patients treated with recombinant human IL-10 suggest the therapeutic potential of this cytokine and underline its impact on the regulation of the skin immune system.

Dermatitis↗
PubMed1999

A high prevalence of cytomegalovirus antigenaemia in patients with moderate to severe chronic plaque psoriasis: an association with systemic tumour necrosis factor alpha overexpression.

Microbiological aspects are considered to be of pathophysiological importance in psoriasis, but there has so far been no information regarding cytomegalovirus (CMV) infection. This is of interest due to the high prevalence of latent infection in the general population, the frequent reactivation in inflammatory diseases, and the immunomodulating capacity of CMV. To detect active infection we analysed CMV antigen expression of peripheral blood mononuclear cells (PBMC) from psoriatic patients (n = 30) in comparison with healthy volunteers (n = 65). Using three monoclonal antibodies and immunocytological staining (alkaline phosphatase-antialkaline phosphatase technique), we frequently found CMV antigenaemia in psoriasis (43%) compared with healthy laboratory staff (12%, P < 0. 01) and blood donors (6%, P < 0.001). Clearance of CMV antigenaemia was observed with antipsoriatic treatment. CMV antigenaemia was symptomless, and was associated with seropositivity for anti-CMV IgG but not IgM antibodies, indicating subclinical activation of latent infection. Serological investigations in 85 psoriatic patients gave no evidence for a higher prevalence of latent CMV infection. In psoriatic lesions, CMV DNA was only rarely detected by polymerase chain reaction. As it has been shown that tumour necrosis factor (TNF)-alpha can induce CMV reactivation, we determined TNF-alpha plasma concentrations and mRNA expression in PBMC from psoriatic patients. Elevated TNF-alpha levels were found and correlated with the frequency of CMV antigen-expressing PBMC, suggesting a critical role of TNF-alpha in CMV activation. We speculate that active, subclinical CMV infection may be of pathophysiological importance in psoriasis.

Administration, Topical↗
PubMed1999

Development of an oligonucleotide probe specific for Trichophyton rubrum.

A species-specific DNA probe was developed to detect the dermatophyte species Trichophyton rubrum. The selected oligonucleotide sequence is derived from the highly variable internal transcribed spacer 2 region of the ribosomal DNA operon. The specificity of the non-radioactive labelled oligonucleotide probe was tested against related dermatophytes, other eukaryotic microorganisms and against human DNA. No cross-hybridization was found, and hybridization signals were invariably detected in all T. rubrum strains investigated. In addition, no homologous sequences were found searching the EMBL database. Experiments to establish a method for isolating DNA directly from clinical specimens gave successful amplification and hybridization products in about 30% of the samples.

Base Sequence↗
PubMed1999

Case report. Osteomyelitis caused by high resistant Candida guilliermondii.

We describe a case of a 57-year-old patient with osteomyelitis at a finger of his right hand caused by Candida guilliermondii. The strains isolated were highly resistant to fluconazole and itraconazole. Using the three methods, microdilution, agardilation and E-test, the highest minimum inhibitory concentrations (MICs) amounted to > 256 micrograms ml-1 for fluconazole and > 32 micrograms ml-1 for itraconazole. To our knowledge, this is the first time such high values have been described for C. guilliermondii. They correlated with the therapeutic non-response to a triazole therapy in our patient. The patient was cured by partial amputation of the affected finger.

Antifungal Agents↗
PubMed1999

Detection of melanoma micrometastases in the sentinel lymph node and in nonsentinel nodes by tyrosinase polymerase chain reaction.

The aim of our study was to investigate the metastatic pathways of melanoma cells in sentinel and other regional lymph nodes. The term "sentinel lymph node" means that the first lymph node of the draining site of a primary tumor is never bypassed in malignant melanoma. In this case lymph node dissection would be necessary only when melanoma cells are detected in the sentinel node. Tyrosinase reverse transcriptase-polymerase chain reaction was applied to search for metastatic melanoma in the sentinel lymph node and in further lymph nodes of a complete lymph node basin in patients who underwent lymph node dissection. In 24 patients with malignant melanoma the draining site of the tumor was marked by lymphoscintigraphy and by intraoperative injection of patent blue V in the area around the primary tumor. The lymph nodes of the affected basin were excised and prepared for histopathologic, immunohistochemical, and molecular biologic examinations. Regarding the sentinel lymph node, 10 of 24 patients showed morphologic evidence for metastases, three additional patients showed only tyrosinase transcripts. In 11 of these 13 cases we found one or more nonsentinel lymph nodes with morphologically detectable melanoma cells and/or tyrosinase mRNA. Interestingly, in seven of 24 patients a positive tyrosinase reverse transcriptase-polymerase chain reaction was received in nonsentinel lymph nodes, whereas the sentinel lymph node was negative, not only for all histologic examinations but also by tyrosinase reverse transcriptase-polymerase chain reaction. In five of seven patients of the latter group, gp100 reverse transcriptase-polymerase chain reaction was carried out, showing also gp100 mRNA in nonsentinel lymph nodes only. Our data indicate that the concept of the sentinel lymph node may miss micrometastases. Whether such micrometastases cause a recurrence or a metastasis of malignant melanoma, or can be destroyed by the immune system, remains to be clarified.

Adult↗
PubMed1999

Mainly unmutated V(H) genes rearranged in B cells forming germinal centers in a cutaneous pleomorphic T-cell lymphoma.

B cells in skin lesions of a pleomorphic cutaneous T-cell lymphoma with reactive germinal center hyperplasia were analyzed for their immunoglobulin V(H)DJ(H) gene rearrangements by micromanipulation and single cell polymerase chain reaction (PCR) analysis. In B lymphocytes located in germinal center-like structures, we found in 11/16 different V(H)DJ(H) rearrangements completely unmutated VH genes, suggesting that those cells did not undergo antigen-driven selection. Two V(H) genes showed more than 98% germ-line identity. In only three cells V(H) segments were somatically mutated to a higher extent, but two of these rearrangements were non-productive. These results differ markedly from what we have previously detected in B cells present in mycosis fungoides, another entity of cutaneous T-cell lymphomas where the Ig gene repertoire resembles the situation in peripheral blood with a significantly higher proportion of mutated V(H) genes. When investigating the large atypical B cells strongly expressing CD30 which were detected within the T-cell zone outside the germinal centers, we found again, in most cases, that the rearranged VH genes were completely unmutated. The B cells were of polyclonal origin. Due to this comparable Ig gene repertoire and mutational pattern, we suggest that these cells descend from the germinal center centroblasts which migrated into the T-cell zone and obviously became stimulated to express the CD30 marker. The micromanipulation technique and molecular analysis on the single cell level may provide an important input into our understanding of the mechanisms of immune regulation in cutaneous lymphomas.

Amino Acid Sequence↗
PubMed1999

Nevoid bag-like soft fibromas.

True nevi and nevoid disorders are defined as visible, circumscribed and long-lasting lesions of the skin, reflecting genetic mosaicism. We report on a 17-year-old young man presenting with large pedunculated soft fibromas restricted to a circumscribed area of the right abdomen. We suggest that these nevoid bag-like soft fibromas represent a new malformation in the heterogenous group of nevoid tumors.

Abdomen↗
PubMed1999

Tinea capitis in Germany. A survey in 1998.

Under the assignment of the ECMM (European Confederation of Medical Mycology) a survey regarding frequency, infectious spectrum and therapy of tinea capitis was conducted in Germany in 1998. In this survey 154 dermatology practitioners and 19 hospitals throughout Germany participated. There were 394 conditions reported, 377 with and 17 without identification of the infectious agent. The most frequent infectious agent was M. canis (n = 216; 54.8%) before T. mentagrophytes (n = 58; 14.7%), T. verrucosum (n = 32; 8.1%), T. violaceum (n = 24; 6.1%) and T. tonsurans (n = 15; 3.8%). Zoophilic dermatophytes (n = 306; 81.2%) predominated over anthropophilic species (n = 71; 18.8%) in the ratio of 4:1. Tinea capitis microsporica showed to be a more frequent infectious disease again which due to its high virulence and contagiosity of the infectious agent represents a therapeutical problem. Tinea capitis occurred in an average age of 17.3 years. The preferred therapeutical regimen was a combination of systemic and topical antimycotics in 61.5% (n = 176) of the reported cases (n = 286). A solely topical or systemical monotherapy was reported in 25.2% (n = 72) respectively 13.3% (n = 38) of the patients. In case of systemic antimycotics the most frequent used drugs were griseofulvin (43.0%, n = 101), fluconazole (25.1%, n = 59) or itraconazole (18.7%; n = 44), in topical preparations ciclopiroxolamine dominated (53.3%, n = 121) prior to clotrimazole (13.2%, n = 30) and terbinafine (7.1%, n = 16). Different from the situation in Germany and in Southern Europe some of the western European countries show a tendency of an increase of anthropophilic agents in tinea capitis.

Germany↗
PubMed1999

The pathophysiological role of cytokines in psoriasis.

Psoriasis is a chronic inflammatory cutaneous disorder. Recent data indicate that T cells and cytokines are of major importance in the pathophysiology of this frequent immune disease. The cutaneous and systemic overexpression of several proinflammatory cytokines, particularly type-1 cytokines such as IL-2, IL-6, IL-8, IL-12, IFN-gamma and TNF-alpha, has been demonstrated. The overexpression of these proinflammatory cytokines is considered to be responsible for initiation, maintenance and recurrence of skin lesions. The cellular composition of the inflammatory infiltrate within the plaques as well as the keratinocyte hyperproliferation appears to be directed by cytokines as well. Thus, the overexpression of the chemoattractant IL-8 contributes to the accumulation of granulocytes, a characteristic finding in psoriatic lesions. In contrast to the overexpression of proinflammatory cytokines, a relatively low level of expression of the antiinflammatory cytokines IL-1RA and IL-10 has been found, suggesting an insufficient counterregulatory capacity in psoriasis which might have a genetic background. The new pathophysiologic understanding of psoriasis offers the opportunity for well-targeted therapeutic interventions which should be more effective and better tolerated than the approaches used thus far. In fact, the cytokine imbalance represents an interesting target. This is supported by the therapeutic effects of IL-10, a type-2 cytokine with major influence on immunoregulation, since it inhibits type-1/proinflammatory cytokine formation.

Journal Article↗
PubMed1998

Prospective randomized multicenter clinical trial on the use of interferon -2a plus acitretin versus interferon -2a plus PUVA in patients with cutaneous T-cell lymphoma stages I and II.

Cutaneous T-cell lymphoma (CTCL) constitutes a malignant proliferative disease involving mostly CD4(+) T cells arising in the skin. Because of the lack of curative treatment options, interferons (IFN) have been introduced into the therapy of CTCL. Although effective even in advanced disease, response rates were about 50% and the duration of response was short. To improve the results of interferon monotherapy, combinations of IFN with oral photochemotherapy (PUVA) or retinoids were investigated in nonrandomized trials showing higher response rates. We have therefore conducted this prospective randomized multicenter trial to compare these two combination therapies, ie, IFN plus PUVA and IFN plus acitretin. IFN -2a was administered at 9 MU three times weekly subcutaneously in both groups, with lower increasing doses during the first week. Photochemotherapy was applied after oral intake of 8-methoxypsoralen (0.6 mg/kg body weight) 5x weekly during the first 4 weeks, 3x weekly from weeks 5 through 23, and 2x weekly from weeks 24 through 48, with escalating doses beginning with 0.25 J/cm2. Twenty-five milligrams of acitretin was administered daily during the first week, and 50 mg was administered from weeks 2 through 48. Of 98 patients randomized in this study, 82 stage I and II patients were evaluable: 40 in the IFN+PUVA group and 42 in the IFN+acitretin group. With 70% complete remissions in the IFN+PUVA group, this treatment was significantly superior to the IFN+acitretin group with only 38.1% complete remissions. Time to response was significantly shorter in the IFN+PUVA group, with 18.6 weeks compared with 21.8 weeks in the IFN+acitretin group. Side effects were mostly mild to moderate and did not differ significantly in both treatment groups. However, there were more adverse events leading to study discontinuation in the IFN+acitretin group. Based on these findings, we conclude that IFN plus oral photochemotherapy is superior to IFN plus acitretin, inducing more complete remissions in patients with CTCL stages I and II.

Acitretin↗
PubMed1998

IL-10 is a key cytokine in psoriasis. Proof of principle by IL-10 therapy: a new therapeutic approach.

Overexpression of proinflammatory, type 1 cytokines has been demonstrated in psoriasis and is believed to be of pathophysiological importance. IL-10 is a type 2 cytokine with major impact on immunoregulation, since it inhibits type 1/proinflammatory cytokine formation. Therefore, we investigated its role in psoriasis. We found a relative deficiency in cutaneous IL-10 mRNA expression compared with other inflammatory dermatoses. Interestingly, patients during established antipsoriatic therapy showed higher IL-10 mRNA expression of peripheral blood mononuclear cells than patients before therapy. This suggested that IL-10 may have antipsoriatic capacity. Therefore, we performed a phase 2 pilot trial with subcutaneous IL-10 administration (8 microg/kg/d) over 24 d in three patients. Clinical efficiency measured by objective and subjective parameters was found. Immunosuppressive effects (depressed monocytic HLA-DR expression, TNF-alpha and IL-12 secretion capacity, IL-12 plasma levels, and responsiveness to recall antigens) as well as a shift toward a type 2 cytokine pattern (increasing proportion of IL-4, IL-5, and IL-10 producing T cells, selective increase in IgE serum levels) were observed. Remarkably, IL-10 administration also enhanced the intracutaneous IL-10 mRNA expression. Our investigations demonstrate the major importance of IL-10 in psoriasis and show that IL-10 administration represents a new therapeutic approach. This is the first report on IL-10 therapy for cutaneous disorders.

Adult↗
PubMed1998

Detection of clonal T cells in cutaneous T cell lymphoma by polymerase chain reaction: comparison of mutation detection enhancement-polyacrylamide gel electrophoresis, temperature gradient gel electrophoresis and fragment analysis of sequencing gels.

Cutaneous T cell lymphomas (CTCL) can be differentiated from benign inflammatory dermatoses by the demonstration of clonal T cells in skin biopsy. As a marker of the T cell clonality, the rearrangement of the T cell receptor (TCR) genes is amplified by polymerase chain reaction (PCR) and subsequently analyzed by several electrophoresis techniques. Since the validity of this approach depends substantially on the separating capacity of the applied electrophoresis technique, we investigated in the present study the lower detection limit and the sensitivity of heteroduplex-loaded polyacrylamide gel electrophoresis on MDE (mutation detection enhancement) gels (HD-MDE PAGE), of heteroduplex-loaded temperature gradient gel electrophoresis (HD-TGGE) and fragment analysis (FA) on sequencing gels. Genomic DNA from formalin-fixed, paraffin-embedded skin biopsies of 53 CTCL specimens and 27 samples of benign dermatoses was analyzed by TCRy PCR followed by electrophoretic separation. Clonality was detected by HD-MDE PAGE in 22, by HD-TGGE in 34, and by FA in 33 of the 53 CTCL cases. Additionally, FA revealed an oligoclonal fragment profile in seven CTCL specimens. In the 27 samples from benign dermatoses, HD-MDE PAGE and HD-TGGE showed the expected polyclonal pattern in 26, and FA in 25 specimens. HD-TGGE and FA detected a clonal pattern down to a dilution of 10(3) monoclonal cells in 10(6) peripheral blood mononuclear cells (PBMC), while HD-MDE PAGE revealed a detection limit of 10(4) monoclonal cells in 10(6) PBMC. In conclusion, HD-TGGE and FA possess a higher sensitivity and lower detection limit than HD-MDE PAGE. Therefore, both former techniques are useful tools for the routine diagnostic procedure. With regard to time and cost, we recommend HD-TGGE.

Cell Separation↗