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Biomedical subjects

N Pimpinelli

Publications and source records attributed to N Pimpinelli.

At least 37 records · Page 2Linked to original sources
PubMed1999

CD30-CD30 ligand interaction in primary cutaneous CD30(+) T-cell lymphomas: A clue to the pathophysiology of clinical regression.

Primary CD30(+) cutaneous T-cell lymphomas (CTCLs) represent a spectrum of non-Hodgkin's lymphomas (NHLs) that have been well defined at the clinical, histologic, and immunologic level. This group, which includes 2 main entities (large cell lymphoma and lymphomatoid papulosis [LyP]) and borderline cases, is characterized by the expression of CD30 antigen by neoplastic large cells at presentation, possible spontaneous regression of the skin lesions, and generally favorable clinical course. Although the functional relevance of CD30 and its natural ligand (CD30L) expression in most cases of NHL is presently undefined, previous studies indicate that CD30L is likely to mediate reduction of proliferation in CD30(+) anaplastic large-cell NHL. No information is currently available concerning the expression of CD30L in primary CD30(+) CTCLs. In this study, we investigated the immunophenotypic and genotypic expression of CD30 and CD30L in different developmental phases of skin lesions (growing v spontaneously regressing). By immunohistochemistry, CD30L expression was detected in regressing lesions only; by molecular analysis, the expression of CD30L was clearly higher in regressing lesions than in growing ones. CD30L, while expressed by some small lymphocytes, was most often coexpressed by CD30(+) neoplastic large cells, as demonstrated by 2-color immunofluorescence and by immunohistochemistry on paraffin sections. Taken together, these data suggest that CD30-CD30L interaction may play a role in the pathobiology of primary cutaneous CD30(+) lymphoproliferative disorders. In particular, CD30L (over)expression might have a major role in the mechanism of self-regression of skin lesions, the most distinctive clinical feature of this cutaneous lymphoma subtype.

Adult↗
PubMed1999

Human keratinocytes cultured without a feeder layer undergo progressive loss of differentiation markers.

Culture of keratinocytes in conventional medium without a mesenchyme-derived feeder layer leads to poor growth and impaired differentiation; however, the exact pathway and degree of differentiation achieved in such conditions is unclear. We have cultured normal human keratinocytes in Rheinwald and Green's medium, on plastic without a feeder layer, in order to investigate the degree of differentiation that they achieve in these conditions. Intermediate filament proteins, tonofibrils and desmosomes were assumed as markers of differentiation and their expression was analyzed by immunohistochemistry and electron microscopy. Before reaching confluence, keratinocytes expressed keratin molecules, as well as vimentin, and formed tonofibrils and desmosomes. The expression of these markers was progressively reduced until confluence and was totally lost thereafter, while cultures could be propagated for at least six passages. On the contrary, reseeding on a feeder layer after the first passage led to rapid cell death. It could be concluded that signals from a feeder layer are relevant to support continuous synthesis of intermediate filaments proteins and formation of tonofibils and desmosomes, and that the derangement of the cytoskeleton in these conditions leads to altered, not simply defective, response to delayed stimulation by a feeder layer.

Biomarkers↗
PubMed1999

A reappraisal of the histopathologic criteria for the diagnosis of cutaneous allogeneic acute graft-vs-host disease.

To determine the validity of the Lerner grading system and review the histopathologic findings of cutaneous acute graft-vs-host disease (aGVHD), 78 skin biopsy specimens from 49 bone marrow transplant recipients were evaluated. Histopathologic sections were independently reviewed twice by 3 pathologists and classified (Lerner system), without knowledge of the patients' clinical evolution. Intraobserver agreement in grading aGVHD was substantial to almost perfect. Interobserver agreement between pairs of observers was moderate to substantial on first review and substantial on second review. Overall, we found an almost perfect agreement in diagnosing Lerner grade III, whereas areas of disagreement occurred with Lerner grades 0, I, and II. Histopathologically, specimens of patients who developed aGVHD (aGVHD-positive) showed significantly higher frequency of epidermal atrophy, spongiosis, diffuse basal vacuolization, more than 3 single necrotic keratinocytes per high-power field, satellitosis, inflammatory infiltrate, with a predominantly lichenoid pattern, lymphocytic exocytosis, and dermal melanophages. When considering skin samples classified as grade I and II, we found statistically significant differences between aGVHD-positive and aGVHD-negative cases only for the presence of inflammatory infiltrate, lymphocytic exocytosis, and satellitosis. Lerner grading is reproducible, although lesser agreement occurred when evaluating grades I and II, and the Lerner grading system should be revised by including the estimate of the inflammatory infiltrate as an additional criterion for grade II.

Acute Disease↗
PubMed1998

Immunophenotypic analysis of normal human dendritic cells isolated from epidermis and dermis.

BACKGROUND: The skin immune system comprises two types of dendritic cells, i.e. CD1a-positive Langerhans cells in the epidermis and CD36-positive dendritic macrophages in the dermis. Dendritic cells can migrate from skin explants into a culture medium. METHODS: We have examined the morphology and immunophenotype of the dendritic cells migrating from epidermal and dermal sheets in vitro. The epidermis and dermis of keratomes of normal human skin were separated with dispase and cultured for 72 h. At this time, the non-adherent cells in the medium were removed, enriched on a metrizamide or Lymphoprep gradient, counted, prepared by cytospin, and labeled for CD1a, CD36, and HLADr. RESULTS: Cells migrating from the epidermis and dermis show many thin projections or a few veils from the cell surface. Approximately four times more cells migrate from epidermal than dermal sheets from the same keratome. CONCLUSIONS: Using methods to separate the epidermis from the dermis, both CD1a-positive Langerhans cells and CD36-positive dendritic macrophages can be obtained from both tissues, although in different numbers.

Antibodies, Monoclonal↗
PubMed1997

Progression of mycosis fungoides is associated with changes in angiogenesis and expression of the matrix metalloproteinases 2 and 9.

Changes in angiogenesis and expression of extracellular matrix-degrading enzymes have been substantiated during progression of solid tumours, whereas information on haematological tumours remains circumstantial. In this study, 57 biopsies of mycosis fungoides (MF), a haematological tumour of T-cell lineage, were investigated immunohistochemically for the extent of angiogenesis, and by in situ hybridisation for the expression of matrix metalloproteinases 2 (MMP-2, collagenase A) and 9 (MMP-9, collagenase B). The biopsies we grouped according to the stage of progression: patch-->plaque-->nodular (most advanced). The extent of angiogenesis, as microvessel area, of MF lesions as a whole was significantly higher than that of normal uninjured skin, used as a control. When the stages of MF progression were compared, the values of MF patch stage overlapped that of control skin, while values were significantly higher in the plaque stage and even higher in the nodular stage. In these stages, microvessels were widely scattered in the tumour tissue, in close association with tumour cells, and they frequently displayed arborisation and microaneurysmatic dilation. In contrast, in the patch stage microvessels were irregularly distributed around the tumour aggregates, and arborisation or dilated structures were only rarely seen. The expression of MMP-2 and MMP-9 mRNAs underwent significant upregulation in relation to advancing stage. Indeed, the upstaging was significantly associated with higher proportions of lesions positive for each mRNA or for both, and with lesions with the greatest intensity of expression for each mRNA. Besides tumour cells, the MMP-2 mRNA was expressed by microvascular endothelial cells of intratumour and peri-tumour vessels, and by fibroblasts which were especially abundant in the stroma adjacent to the tumour nodules. The MMP-9 mRNA was found to be present in a subset of tissue macrophages which were more frequently located in close vicinity to the tumour nodules. In contrast, in control skin, a weak positivity for the MMP-2 mRNA in very few microvascular endothelial cells and no signal for the MMP-9 mRNA were observed. These in situ data suggest that angiogenesis and degradation of the extracellular matrix occur simultaneously during MF progression. They imply that interaction between tumour cells and their microvasculature are all the more likely to occur during progression, occasionally with the contribution of tumour-associated stromal cells.

Aged↗
PubMed1997

Oral keratinocyte immune responses in HIV-associated candidiasis.

INTRODUCTION: Candidiasis is the most commonly encountered opportunistic infection among HIV-positive subjects. The purpose of this study was to assess specific keratinocyte immune parameters in the pseudomembranous and erythematous forms of HIV-associated oral candidiasis. MATERIAL/METHODS: This collaborative study from three centers analyzed 25 HIV-positive and 10 HIV-negative subjects with either pseudomembranous or erythematous candidiasis. Oral biopsy specimens from lesional tissues were procured, and histopathologic features were correlated with immunohistochemical and in situ hybridization investigations for the expression of interleukin 1 alpha, interleukin 8, antimicrobial calprotectin, lymphocyte populations, and Candida antigen. RESULTS: Both pseudomembranous and erythematous candidiasis among HIV-infected subjects showed a mild interface lymphocytic mucositis with the presence of neutrophilic subcorneal abscesses in the latter. Erythematous candidiasis cases that failed to show surface mycelia, did yield positive results for Candida antigens in the parakeratinized layer. The expression of inflammatory chemokines were positive in all groups and calprotectin appeared to serve as a keratinocyte barrier to hyphal penetration. CONCLUSIONS: The erythematous form of candidiasis is often devoid of hyphae yet the presence of Candida antigens in the surface epithelium implicates an immune or allergic process. The intactness of chemokines and antimicrobial calprotectin in keratinocytes may explain why disseminated candidiasis is rarely encountered in HIV-infected patients.

AIDS-Related Opportunistic Infections↗
PubMed1997

Immunocompetent cells in oral candidiasis of HIV-infected patients: an immunohistochemical and electron microscopical study.

OBJECTIVE: The purpose of this study was to elucidate the pathogenesis of oral candidiasis, a common cause of discomfort and social impairment among HIV-infected individuals. STUDY DESIGN, MATERIALS AND METHODS: The oral mucosal immune system cells were analysed by immunohistochemistry and electron microscopy in biopsies from five erythematous and four pseudomembranous candidiasis cases and were compared with those from seven HIV-positive and 10 HIV-negative controls without candidiasis. RESULTS: The superficial lamina propria and basal epithelial layer was populated by CD1a+ Langerhans cells with infiltration of CD8+ lymphocytes. Within the submucosa are CD36+ dendritic macrophages and lymphocytes, although CD4+ subsets were absent from the infiltrate. The expression of human leukocyte antigen system, DR locus (HLA-DR) and leukocyte specific adhesion molecules was low in erythematous, yet more marked in pseudomembranous candidiasis. In the pseudomembranous form, CD14+ leukocytes were found in the basal epithelial layer. Langerhans cells were significantly more numerous and were richer in dendrites and Birbeck granules in erythematous than in pseudomembranous candidiasis. CONCLUSIONS: Candidiasis is associated with alterations in the number and differentiation of lymphocytes and dendritic cells, being more severe in the pseudomembranous than erythematous form. We propose that these alterations play a role in the pathogenesis and evolution of the disease.

AIDS-Related Opportunistic Infections↗
PubMed1997

Extracorporeal photochemotherapy induces a significant increase in CD36+ circulating monocytes in patients with mycosis fungoides.

BACKGROUND: In patients with Sezary syndrome undergoing extracorporeal photochemotherapy it is currently thought that photodamage of a congruent number of pathogenic circulating T cells is a necessary condition for a specific anticlonal response to be induced against these cells by the immune system. However other mechanisms of action, such as the induction of release by photoirradiated monocytes of some cytokines, are thought to cooperate in the induction of a therapeutic response. OBJECTIVE: We investigated the effects of extracorporeal photochemotherapy on peripheral blood mononuclear cells in seven stage Ib cutaneous T cell lymphoma patients. METHOD: Samples of peripheral blood were taken before starting extracorporeal photochemotherapy (baseline), and before the 3rd and 6th cycle of treatment, and then incubated with specific monoclonal antibodies. RESULTS: The results showed a significant increase of CD8+ and CD36+ and a significant decrease of CD25+ in all the treated patients. CONCLUSION: Our results show that extracorporeal photochemotherapy is able to induce an increase of CD36+ cell in peripheral blood of patients with mycosis fungoides in its early stages. This subset of monocytes could be involved in the complex mechanism of action of extracorporeal photochemotherapy.

Aged↗
PubMed1996

Cyclosporin-A affects the organization of cytoskeleton of normal human keratinocytes in culture.

Cyclosporin-A (CsA) is a potent immunoregulatory molecule which has been widely used in many immunomediated and inflammatory skin diseases. It inhibits the proliferation of keratinocytes, but its possible effects(s) on cell differentiation are poorly known. To address this issue, we have studied the influence of CsA on the assembly of intermediate filaments by normal human keratinocytes in culture. Control keratinocytes were flat; the cells which had not reached confluence stained intensely for vimentin and weakly for cytokeratins; confluent cells stained with intermediate intensity for both types of proteins and the cells adhering on the top of others, interpreted as the best differentiated ones, stained for cytokeratins but not for vimentin. CsA (1.6 micrograms/ml for 10 days) inhibited the growth of keratinocytes, which never reached confluence; most cells appeared small and roundish, only some stained for cytokeratins and few for vimentin. By electron microscopy, a well organized meshwork of tonofibrils was recognized in many control keratinocytes, but never in CsA-treated keratinocytes. We propose that the cytoskeleton could be a target of CsA and that its alteration mediates other effects of CsA on keratinocytes, including those on cell growth.

Antibodies, Monoclonal↗
PubMed1994

Dendritic cells in cutaneous lupus erythematosus: a clue to the pathogenesis of lesions.

In view of the critical role of dendritic cells in immune mediated skin diseases, we have investigated the membrane antigen patterns and ultrastructure of cutaneous dendritic cells in eight patients with chronic discoid lupus erythematosus and five with subacute cutaneous lupus erythematosus. In the lesional epidermis, the expression of HLA-DR antigens by epidermal dendritic cells was reduced, as compared with perilesional, clinically normal skin. In addition, only few CD1a+ dendritic cells (Langerhans' cells), along with some CD11c+ and CD14+ cells (presumable precursors of Langerhans' cells), were found in atrophic areas of lesional epidermis. In contrast, the number of Langerhans' cells in non-atrophic areas of lesional epidermis was similar to that in perilesional skin. On electronmicroscopy, epidermal Langerhans' cells appeared depleted of organelles and dendrites and contained tubuloreticular inclusions. In the lesional dermis, both CD1a+ and CD36+ dendritic cells were found, associated with CD4+ and CD8+ T-cells, respectively. Moreover, CD11c+ and CD14+ cells were found around capillaries in the papillary dermis on electronmicroscopy. Indeterminate cells (dendritic cells with features of Langerhans' cell lineage, but apparently without Birbeck granules) and dendritic macrophages were found, associated with lymphocytes and mast cells. No cells with intermediate/transitional features between these two dendritic cell types were found. Conversely, peculiar dendritic cells--with short and blunt dendrites and cytoplasm containing many flat, rough cisternae, moderately well developed Golgi apparatus and no lysosomes--were found in the same location as the CD11c+ and CD14+ cells identified by light microscopy. These findings might be interpreted as follows: 1 the alterations in cytological differentiation and expression of functionally meaningful molecules by epidermal Langerhans' cells in cutaneous lupus erythematosus lesions suggest an impairment of their immunological efficiency; 2 in the lesional dermis of cutaneous lupus erythematosus, a CD4+ T-cell/CD1a+ dendritic cell-based, delayed-type immune response is possibly modulated by a suppressor T-cell circuit in which CD36+ dendritic cells may act as accessory cells; 3 CD11c+ and CD14+ cells with peculiar ultrastructure are possible precursors of both CD1a+ indeterminate cells and CD36+ dermal dendrocytes in the dermis.

Adolescent↗
PubMed1994

Topical corticosteroids and unwanted local effects. Improving the benefit/risk ratio.

The main goal of pharmacological research in the field of topical corticosteroids (TCs) is to dissociate efficacy and adverse effects as much as possible. The optimal use of TCs, i.e. the careful evaluation of the benefit/risk ratio, depends on: (i) the chemical structure of the TC; (ii) the type of vehicle; (iii) the mode of application; and (iv) the features of the skin to be treated. The recent availability of TCs characterised by a good dissociation between efficacy and adverse effects makes the classic and widely used classification system of TCs based upon potency out of date. Indeed, TCs with increasing potency have been characterised up to now, as a rule, by an increasing risk of adverse effects. Therefore, a classification system taking into major account the benefit/risk ratio seems particularly needed for clinical use in dermatology.

Administration, Topical↗
PubMed1994

Dendritic cells in T- and B-cell proliferation in the skin.

In lymphoproliferative diseases of the skin, DC have a key role in T- and B-cell homing. Furthermore, DC alterations may have a pathogenic role in the natural history of specific disorders, either in the neoplastic lymphoid cell progression or in antitumoral lymphocyte reaction. Finally, the morphoantigenic and topographic features of DC may have diagnostic and histogenetic relevance in specific conditions. In CTCL, dermal CD1a+ DC ("indeterminate cells") seem to play a significant role in the neoplastic progression of MF, whereas the possible pathogenetic role of specific alterations of epidermal LC is yet to be proven. Recently, a possible implication of DD (resident, perivascular factor XIIIa+/CD1a- DC) in the pathogenesis of MF has been also suggested. The presence and possible significance of DC in CTCL non-MF are presently poorly studied. At present, DC number, distribution, and phenotype seem possibly useful in the differential diagnosis between CTCL and pseudo-CTCL, but this hypothesis has to be adequately confirmed. CBCL has been recently proposed as a unique type of clinically low-grade lymphoma, namely, skin-associated lymphoid tissue (SALT)-related B-cell lymphoma. Both SALT- and mucosa-associated lymphoid tissue (MALT)-related B-cell lymphoma share with a peculiar nodal lymphoma of follicle mantle origin (parafollicular-monocytoid lymphoma) the nonaggressive clinical behavior and the uniform phenotype (CD5-, CD10-) and genotype (lack of bcl-2 gene rearrangement) of neoplastic B cells, despite the wide variability of cytomorphologic appearances. The putative origin of CBCL is further supported by the typical CD14-, nerve growth factor receptor (NGFr)+ immunophenotype of DRC. Moreover, the immunophenotype and architectural fashion of DRC are interesting clues to the differentiation between neoplastic and true reactive folliclelike nodules and may be of help in the differential diagnosis between CBCL and B-cell pseudolymphoma as well as in the correct interpretation of lesions showing monoclonal proliferations of B cells accompanied by polyclonal follicular reactions.

B-Lymphocytes↗
PubMed1992

Topical corticosteroids. Which drug and when?

A number of factors have to be taken into account when dealing with the treatment of skin diseases with topical corticosteroids, including disease type and phase, potency of the drug, safety, site to be treated, age of the patient, and drug formulation. Concerning the specific indications for topical corticosteroid treatment, we can distinguish skin diseases in which: (a) topical corticosteroids are the treatment of choice; (b) topical corticosteroids are useful as alternative and/or adjuvant treatment; (c) the proposed use of topical corticosteroids has to be confirmed as useful; and (d) topical corticosteroids can be used as a symptomatic treatment. Within these groups, the treatment schedule has to be adjusted according to the above mentioned general factors.

Administration, Topical↗