Biomedical subjects

Werner Kempf

Publications and source records attributed to Werner Kempf.

48 records · Page 3Linked to original sources

PubMed2003

Proliferation of CD30+ T-helper 2 lymphoma cells can be inhibited by CD30 receptor cross-linking with recombinant CD30 ligand.

PURPOSE: Cutaneous anaplastic large cell lymphomas (ALCLs) are characterized by the expression of CD30, spontaneous regression of skin lesions, and increased concentration of CD30 ligand (CD30L). We hypothesize that CD30-CD30L interactions explain the unusual clinical behavior of cutaneous ALCLs. EXPERIMENTAL DESIGN: Eight lymphoma cell lines established from four different patients were analyzed for T-cell clonality using PCR and subsequently denaturating gradient gel electrophoresis. The expression levels of CD30 were assessed by flow cytometry. Secreted cytokines [IFN-gamma, interleukin (IL)-2, IL-4, IL-6, IL-8, and IL-10] were determined in the supernatant after 3-day culture. Proliferation and apoptosis of cultured cells were measured by 5-bromo-2-desoxyuridine and propidium iodine incorporation. RESULTS: The results showed different levels of CD30 expression and a predominant T-helper 2 profile. In a cell kinetic analysis we found that ALCL cell growth is effectively inhibited by CD30L but only in those cell lines expressing CD30 molecules in sufficient amounts on the cell surface. Cell cycle analysis revealed that growth regulation was because of apoptosis and growth arrest, and was dependent on cell culture conditions. Comparison of effects of ligation with CD30L and anti-CD30 agonistic antibody HeFi-1 revealed higher efficacy for CD30L in these ALCL lines. CONCLUSIONS: CD30+ ALCL cells can be growth inhibited by receptor ligation. Observed pleiotropic effects of CD30 signaling are most likely dependent on cell cycle status and signal strength. The binding of CD30 by its ligand provides new opportunities for controlling cell growth and treatment of CD30+ ALCL.

Apoptosis↗

PubMed2002

HLA-G protein up-regulation in primary cutaneous lymphomas is associated with interleukin-10 expression in large cell T-cell lymphomas and indolent B-cell lymphomas.

Primary cutaneous lymphomas (CLs) constitute a spectrum of diseases characterized by a clonal accumulation of lymphocytes in the skin. Most CLs display a T(h)2 cytokine profile, including expression of interleukin-10 (IL-10). Because the up-regulation of HLA-G, a nonclassical class Ib molecule inducible by IL-10, might account for the immunescape of the malignant clone, HLA-G and IL-10 expression has been investigated in 45 cases of primary CL (10 of B-cell and 35 of T-cell origin) with quantitative polymerase chain reaction (PCR) and immunohistochemistry. HLA-G message was present in all cutaneous B-cell (CBCL) and T-cell (CTCL) lymphomas evaluated. Immunohistochemistry revealed HLA-G protein expression in 23 (51%) of 45 cases (7 of 10 CBCL, 16 of 35 CTCL). While in CBCL mostly indolent types displayed HLA-G positivity, in CTCL HLA-G expression was associated with high-grade histology and advanced stage of the disease. Except for neoplastic and infiltrating lymphocytes, other cells such as macrophages and dendritic cells showed HLA-G immunoreactivity. Furthermore, IL-10 protein expression was demonstrated in 16 (73%) of 22 HLA-G(+) cases, which correlated with HLA-G protein presence (P <.001). HLA-G up-regulation together with IL-10 expression in CL might additionally contribute to the evasion of immunosurveillance and facilitate the transition from low- to high-grade lymphomas.

Adolescent↗

PubMed2002

Junctional CD8+ cutaneous lymphomas with nonaggressive clinical behavior: a CD8+ variant of mycosis fungoides?

OBJECTIVE: To evaluate the clinical and prognostic features in primary cutaneous CD8+ T-cell lymphomas, which are rare and considered to be aggressive cutaneous lymphoproliferative disorders. DESIGN: Single-center retrospective study. SETTING: Lymphoma clinic (referral center) of a university hospital. PATIENTS: Three patients presented with CD8+ cutaneous lymphoma characterized by a patchlike pattern and hyperpigmentation. RESULTS: Histological analysis revealed a CD3+, CD8+ small-cell infiltrate showing a remarkable affinity to the dermoepidermal junction zone. Clonality for the T-cell receptor gamma chain was detected by polymerase chain reaction followed by denaturing gradient gel electrophoresis. The clinical presentation lasted several years (6 and 9 years, respectively) before the correct diagnosis was made. Treatment with nontoxic approaches (UV-B and local steroids) was successful. Aggressive clinical behavior was not observed. CONCLUSIONS: Our 3 cases of junctional CD8+ cutaneous T-cell lymphomas were characterized by hyperpigmentation and nonaggressive clinical behavior. This type of lymphoma, which can be considered a CD8+ mycosis fungoides variant, must be distinguished from other types of cutaneous CD8+ lymphomas so that overtreatment can be avoided.

Adult↗

PubMed2002

From inflammation to neoplasia: new concepts in the pathogenesis of cutaneous lymphomas.

Mycosis fungoides is a clinicopathologic term which describes a neoplasm of cerebriform T lymphocytes that form plaques and tumors. We further suggest that mycosis fungoides arises in a background of chronic inflammation or as a response to chronic antigenic stimulation. Subsequently, a series of mutations results in the stepwise progression from eczematous patches, to plaques, tumors and eventual hematogenous dissemination. The pathogenetic process is driven by various, probably individually different, exogenous factors, e.g. environmental foreign antigens, bacterial superantigen, and/or endogenous factors, e.g. autocrine cytokine loops, CD40/CD40L and B7/CD28 interaction.

Humans↗

PubMed2002

Cutaneous lymphomas and pseudolymphomas: newly described entities.

This chapter summarizes some recently described cutaneous lymphomas and pseudolymphomas with regard to their clinicopathological presentation, biological behavior and classification place. Among cutaneous lymphomas, the group of cytotoxic lymphomas, angioimmunoblastic T-cell lymphoma, intravascular lymphoma, hydroa-like lymphoma, marginal zone lymphoma, spindle-cell B-cell lymphoma, and B-cell lymphoma with a dermatomal distribution are presented. In the context of pseudolymphomas, cutaneous follicular lymphoid hyperplasia with monotypic plasma cells, pleomorphic reactions in molluscum contagiosum, and CD30+ reactions to parapoxvirus are discussed.

Humans↗

PubMed2002

Primary cutaneous plasmacytoma: a clinicopathological study of two cases with a long-term follow-up and review of the literature.

BACKGROUND: Primary cutaneous plasmacytoma (PCP) is a rare type of cutaneous B-cell lymphoma arising primarily in the skin and derived from clonally expanded plasma cells with a various degrees of maturation and atypia. The disease is rare with only 30 cases reported so far. METHODS: Two cases of PCP with long-term follow-up of 17 and 15 years are presented. RESULTS AND CONCLUSIONS: Both patients were men with nodular lesions on the face. Histologically, the lesions were composed predominantly of variably maturated plasma cells with monotypic expression of immunoglobulin (Ig) lambda chains. Polymerase chain reaction for IgH genes did not reveal clonal rearrangement. Our cases are discussed in the context of previously reported cases of PCP with a long-term follow-up. We also include a review of all cases of PCP with known tumor progression earlier in the course of the disease (local relapse or visceral spread) to determine the clinical course of this primary cutaneous lymphoma.

Adult↗

PubMed2002

Study of HHV-8 DNA sequences in archival biopsies from lesional skin of Kaposi's sarcoma, various mesenchymal tumors and related reactive conditions.

BACKGROUND: HHV-8 has been identified as the causative agent of Kaposi's sarcoma (KS) and some lymphoproliferative disorders. In addition, there are anecdotal reports on the presence of HHV-8 in other tumors, especially cutaneous epithelial and mesenchymal neoplasms. The aim of the study was to ascertain the value of identification of HHV-8 viral DNA sequences in routinely processed, formalin-fixed, paraffin-embedded tissues for the diagnosis of Kaposi's sarcoma and other mesenchymal tumors. METHODS: The presence of HHV-8 sequences in archival material was studied by nested PCR using specific primers for amplification of a 233-bp long fragment of HHV-8 (ORF 26). RESULTS: Thirty-three patients with KS (18 classic/sporadic, six post-transplant and nine AIDS-related) and various mesenchymal tumors and related conditions (n = 76) were studied. HHV-8 DNA sequences were detected in 29 of the 33 cases of KS and in one case of multiple eruptive dermatofibroma (MEDF). CONCLUSIONS: Identification of HHV-8 DNA sequences in routinely processed tissue is a useful diagnostic marker for KS. Although other mesenchymal tumors are usually not associated with HHV-8, its presence is not fully specific for KS since HHV-8 sequences were also found in one case of MEDF. Therefore, PCR analysis for the detection of HHV-8 should only be used as an additional diagnostic marker for KS and in the context of other tools such as routine histology.

AIDS-Related Opportunistic Infections↗

PubMed2002

Fascin expression in CD30-positive cutaneous lymphoproliferative disorders.

BACKGROUND: CD30-positive cutaneous lymphoproliferative disorders (LPD) represent a spectrum of diseases ranging from low-grade (lymphomatoid papulosis; LyP) to high-grade (pleomorphic and anaplastic large-cell lymphoma; PTL, ALCL) with overlapping morphologic and immunophenotypic features. The common phenotypic hallmark is the expression of CD30-antigen by the tumor cells which morphologically resemble Reed-Sternberg cells. Although LyP is a non-fatal recurring disorder, it is associated with systemic lymphomas including Hodgkin's lymphoma (HL), mycosis fungoides (MF) and ALCL in 5-20% of the cases. Currently there is no marker to predict the development of systemic lymphomas in patients with LyP. Fascin, an actin bundling protein, has recently been shown to be a unique marker found in almost 100% of classical HL. METHODS: Because of the association of LyP with HL, fascin expression was analyzed by immunohistochemistry in LyP (n = 45), cutaneous CD30+ ALCL (n = 17) and pleomorphic T-cell lymphoma (n = 9) (PTL) and LyP associated with systemic lymphomas (7 HL, 2 ALCL, 1 MF), with the intent to determine if fascin expression can predict disease progression. RESULTS: Fascin was expressed by tumor cells in 11/45 (24%) cases of LyP, 11/17 (64%) cases of ALCL, 7/9 (77%) cases of PTL and 6/10 (60%) cases of LyP associated with systemic lymphomas. Fascin expression in LyP was significantly less frequent than in ALCL (p < 0.001) and also than in LyP associated with lymphomas (p < 0.05). There was no significant difference of fascin expression within the histological subtypes of LyP. We found no evidence of ALK expression nor of Epstein-Barr virus expression in any case either by in situ hybridization or immunohistochemistry in the LyP cases associated with HL. CONCLUSIONS: This is the first study to demonstrate that fascin is expressed in cutaneous CD30+ LPD and that it is a candidate marker of disease progression in LyP.

Biomarkers, Tumor↗

PubMed2002

Angiolymphoid hyperplasia with eosinophilia: evidence for a T-cell lymphoproliferative origin.

Angiolymphoid hyperplasia with eosinophilia (ALHE) is commonly regarded an angioproliferative process characterized by the presence of prominent, bizarrely shaped blood vessels. These vessels are accompanied by an inflammatory infiltrate that is thought to be a reactive component. Both the cell of origin and the pathogenesis of ALHE remain controversial. To define the histogenesis of this disorder, we analyzed the phenotypic and genotypic profile of the inflammatory infiltrate in ALHE by immunohistochemistry and T-cell receptor gene rearrangement by polymerase chain reaction (PCR) and denaturing gradient gel electrophoresis, as well as automated high-resolution PCR fragment analysis. Five of 7 ALHE patients displayed a clonal T-cell population and proliferative T-cell activity in lesional tissue. Most of these cases followed a protracted and therapy-reluctant course with recurrences. These data suggest that ALHE or a subset of ALHE cases harboring a clonal T-cell population may represent a T-cell lymphoproliferative disorder of a benign or low-grade malignant nature.

Adult↗

PubMed2002

Human herpesvirus 7 in dermatology: what role does it play?

Human herpesvirus 7 (HHV-7) was discovered in 1989 as a new member of the beta-herpesvirus subfamily. Primary infection occurs early in life and manifests as exanthema subitum, or other febrile illnesses mimicking measles and rubella. Thus, HHV-7 has to be considered as a causative agent in a variety of macular-papular rashes in children. In addition, HHV-7 was found in some cases of other inflammatory skin disorders, such as psoriasis. There are controversial data on the detection of HHV-7 in pityriasis rosea, but so far there is not enough evidence for a pathogenetic association of HHV-7 with this exanthematic skin disease. Although HHV-7 can be found in some cases of Hodgkin's disease, there are no data supporting a direct causative role in this lymphoma type nor in other nodal or primary cutaneous lymphomas. In various epidemiologic forms of Kaposi's sarcoma, infection of monocytic cells with HHV-7 was demonstrated, which may indirectly influence tumor biology. In the context of immunosuppression, HHV-7 has recently been identified as an emerging pathogen in transplant recipients and may exacerbate graft rejection in renal transplant recipients. The ability of HHV-7 to induce cytokine production in infected cells could make HHV-7 an important pathogenetic co-factor in inflammatory and neoplastic disorders. Moreover, the restricted cellular tropism of HHV-7 may render this virus an interesting vector for gene therapy. Thirteen years after the discovery of HHV-7, there has been considerable progress in characterizing its genetic structure, virus-induced effects on infected host cells and in the development of diagnostic tools. Nevertheless, the role of HHV-7 in various skin diseases and the clinical manifestations of reactivation of HHV-7 infection have still to be defined.

Herpesvirus 7, Human↗

PubMedDate not supplied

Pityriasis rosea--an update.

Recent controversies on the etiology, diagnosis and treatment have led to increased interest in pityriasis rosea (PR). We review these aspects of the disease. PR is universal. The incidence is around 0.68 per 100 dermatological patients, or 172.2 per 100,000 person-years. The prevalence in people aged between 10 and 29 years is 0.6%. The male to female ratio is around 1:1.43. Evidence on seasonal variation is conflicting, but there is no evidence that the incidence is dependent on mean air temperature, mean total rainfall, or mean relative humidity. Spatial-temporal and temporal clustering of cases of PR has been reported. The association of PR with human herpesvirus-7 infection is still controversial. Owing to the extreme high sensitivities of sequence-based detection methods such as polymerase chain reaction, novel criteria should be applied to evaluate the evidence. There is no evidence that PR is associated with other viral or bacterial infections. The role of autoimmunity in PR warrants further investigations. Many patients with PR have one or more atypical features. Application of validated diagnostic criteria may be helpful for atypical cases. The efficacy of macrolides, including erythromycin, in PR is still under evaluation. There is no evidence that antiviral agents are effective. The efficacies of ultraviolet radiotherapy and systemic corticosteroids are not well established. In managing a patient with PR, we should concentrate more on how the eruption is affecting the quality of life, i.e. the illness, rather than the extent and severity of the eruption, i.e. the disease.

Anti-Bacterial Agents↗

PubMedDate not supplied

Familial occurrence of axillary papular mucinosis.

Primary cutaneous mucinosis encompasses a wide range of different skin conditions with circumscribed, follicular or diffuse manifestation. For the first time, to our knowledge, we report on the occurrence of so-called "atypical" localized papular mucinosis in the axillary pits of a mother and her (identical) twin daughters presenting as asymptomatic soft minuscule papules. This unique observation allows us to define an autosomal dominant inheritance pattern with a high level of penetrance for this rare skin disease.

Adolescent↗