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Biomedical subjects

E Berti

Publications and source records attributed to E Berti.

At least 19 recordsLinked to original sources

Immunohistochemical evidence of cytokine networks during progression of human melanocytic lesions.

Melanoma cells in culture express a variety of growth factors and cytokines and some of their autocrine and paracrine roles have been investigated. However, less information is available on the potential dynamic changes in expression of these molecules on cells during melanoma development and progression in situ. Using immunohistochemistry, we tested 40 nevi and primary and metastatic melanoma lesions for the expression of 10 growth factors and cytokines and the respective receptors representing 10 cell surface molecules. Nevi and thin (< 1 mm) primary melanomas showed little expression of ligands except weak reactivity of tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), interleukin-8 (IL-8) and reactivity of TGF-betaR and c-kit. Marked up-regulation of growth factors, cytokines and receptor expression was observed in thick (> 1 mm) primary melanomas, which were stained with polyclonal or monoclonal antibodies (MAbs) for IL-1alpha, IL-1beta, IL-6, IL-8, TNF-alpha, TGF-beta, granulocyte-macrophage colony-stimulating factor (GMCSF) and stem cell factor (SCF), but not IL-2. Metastases showed similar expression patterns except that SCF was absent. Co-expression of ligand and receptor was observed for TGF-beta, GM-CSF and IL-6, suggesting an autocrine role for these ligands. TNF-alpha appears to be a marker of benign lesions; IL-6 and IL-8 expression is associated with biologically early malignancy; TGF-beta, GM-CSF and IL-1alpha are highly expressed in biologically late lesions; and TNF-beta is an apparent marker of metastatic dissemination. Our results indicate that melanoma cells utilize cascades of growth factors and cytokines for their progression.

Adult

The perikaryal surface of spinal ganglion neurons: differences between domains in contact with satellite cells and in contact with the extracellular matrix.

The perikaryal surface of spinal ganglion neurons undergoes dynamic changes throughout life. In particular, numerous slender projections develop and retract continuously from this surface. We showed previously that the outgrowth of these projections, while an intrinsic property of spinal ganglion neurons, is also influenced by the surrounding microenvironment. Since the latter consists of satellite cells and the extracellular matrix, we sought to determine the relative contributions of each of these components to the outgrowth of perikaryal projections. To this end, we took advantage of a little known characteristic of the satellite cell sheaths: in the rabbit, these sheaths can exhibit gaps that leave the nerve cell body surface directly exposed to the extracellular matrix. We compared the surface domains covered by satellite cells with those in direct contact with the extracellular matrix. We found that the perikaryal projections are abundant in the former domains but are absent in the latter. We also found that the perineuronal extracellular matrix of rabbit spinal ganglia contains laminin and fibronectin, two glycoproteins that have been reported to promote the growth of axonal processes from sensory ganglion neurons. Laminin and fibronectin were also present at the level of the gaps in the satellite cell sheath. These results: (1) provide additional evidence that environmental factors influence the outgrowth of perikaryal projections from spinal ganglion neurons; (2) suggest that satellite cells permit the outgrowth of these projections; (3) suggest that in the spinal ganglia of adult rabbits the perineuronal extracellular matrix is not in itself able to promote the outgrowth of these projections. This study provides a further example of the influence that supporting neuroglial cells have on sensory ganglion neurons.

Animals

Cutaneous CD30+ lymphoproliferative disorders: expression of bcl-2 and proteins of the tumor necrosis factor receptor superfamily.

The spectrum of CD30+ cutaneous lymphoproliferative disorders is characterized by the histology of a high-grade lymphoma but frequent clinical regression of skin lesions in lymphomatoid papulosis (LyP) and occasional regression in CD30+ large cell lymphomas (LCLs). A recent study shows that apoptosis may be a significant mechanism of regression of LyP (Arch Dermatol 133:828-833, 1997). Therefore, we studied expression of proteins that induce apoptosis, including CD27, CD40, CD95, and nerve growth factor receptor (NGF-R), as well as anti-apoptotic protein bcl-2 in skin lesions from 25 patients within the spectrum of CD30+ cutaneous lymphoma. Our results show consistent expression of CD95 (APO-1/Fas), but rare or absent expression of CD27, CD40, and NGF-R on tumor cells from both regressing LyP lesions and nonregressing CD30+ lymphomas. Bcl-2 was expressed at low levels in LyP and at high levels in pleomorphic CD30+ lymphomas. These results indicate that, in addition to CD30, CD95 expression is preferentially expressed at high levels in all cutaneous CD30+ lymphomas and suggest that CD95 may play a role in the regression of CD30+ skin lesions. Expression of bcl-2 appears to protect tumor cells from apoptosis in CD30+ lymphoproliferative disorders.

Adult

Unusual hyperpigmentation developing in congenital reticular ichthyosiform erythroderma (ichthyosis variegata).

We present an unusual new clinical feature which developed in a patient with congenital reticular ichthyosiform erythroderma. This rare ichthyotic disorder is characterized by erythematous ichthyotic skin surrounding slowly enlarging areas of normal skin, and by a pathognomonic ultrastructural pattern, namely perinuclear deposits of a filamentous material in vacuolized keratinocytes. At the age of 18 years, a 23-year-old woman developed several irregular hyperpigmented macules on her limbs, which were almost black in colour. These lesions have not been observed in the other patients affected by the disease nor, to our knowledge, in other ichthyotic disorders. Electron microscopy and immunohistochemistry demonstrated that the lesions were strictly related to the ichthyotic skin and that their dark colour was especially due to melanosome accumulation in activated dendritic melanocytes. An unusual postinflammatory hyperpigmentation, in which the lack of pigment deposition in the keratinocytes is due to a transfer defect in pathological cells, is hypothesized. A characteristic hyperplastic stimulation of the epidermis is also taken into consideration to explain the lack of a similar picture in other erythrodermic ichthyotic disorders with a continuous inflammatory process.

Adult

Mometasone furoate decreases adhesion molecule expression in psoriasis.

The topical corticosteroids are widely used in the treatment of moderate psoriasis, because of their usefulness for reducing inflammation and controlling itching. The therapeutic effect of corticosteroids in different cutaneous inflammatory diseases may be partially explained by their varying ability to block in vitro the synthesis of different cytokines, which play a pivotal role in epidermal hyperproliferation and leukocyte recruitment into the skin. The purpose of the present investigation was to further elucidate the mode of action of mometasone furoate, a medium-high potency, topical corticosteroid, on adhesion molecules, cytokines and cytokine receptor expression in psoriatic skin. Using an immunohistochemical assessment, we examined lesional skin biopsies from ten psoriatic patients before treatment and after 1 and 3 weeks of therapy. The overexpression of alpha 2, alpha 3, alpha 6, and beta 1 integrins detected in the spinous layer of untreated psoriatic skin was significantly decreased after therapy in 8 out of 10 cases, characterized by only partial clinical remission. In the remaining patients, a disappearance of the above integrin reactivity paralleling the disappearance of psoriatic lesions was induced by the treatment. With the exception of GM-CSF, no or only marginal effects of mometasone furoate on the cytokine and cytokine receptor system were observed. A significant reduction of the positive immunostaining with anti-ICAM-1 and ICAM-2 monoclonal antibodies on dermal vascular endothelial cells was also seen. Thus, our findings indicate that the therapeutic effects of mometasone furoate in psoriasis are mediated principally by decreasing adhesion molecule expression and to a lesser degree by inhibiting cytokine synthesis.

Administration, Cutaneous

Risk of Kaposi's sarcoma-associated herpes virus transmission from donor allografts among Italian posttransplant Kaposi's sarcoma patients.

Kaposi's sarcoma-associated herpesvirus (KSHV) is a newly discovered herpes virus found in all forms of Kaposi's sarcoma (KS) including KS among immunosuppressed transplant patients. It is unknown whether this virus is transmitted by organ transplantation or is reactivated during immunosuppression among those patients infected before transplantation. To investigate the risk of KSHV transmission during organ transplantation, we conducted a case-control study of transplant recipients with and without KS matched to their respective donors. Sera were collected at time of transplantation and tested in a randomized and blinded fashion using four KSHV serologic assays testing for antibodies to both latent and lytic phase antigens. Ten (91%) of 11 organ recipients who developed KS were seropositive prior to transplantation by one or more of the assays compared with two (12%) of 17 control organ recipients (OR = 75, 95% CI = 4.7, 3500). KS cases were more likely to have been born in southern Italy where KS is endemic than the recipient controls or either donor group. Only four (36%) of 11 donors to case patients and three (18%) of 17 donors to control patients were seropositive (P = .38, two-tailed Fisher's exact test). KSHV transmission could not be ruled out for the single KS patient seronegative at transplantation and clear evidence for organ-related transmission was found for another KS patient outside of the case-control study. Antibodies to KSHV are detectable in the sera from most transplant recipients before initiation of immunosuppressive treatment suggesting that KS among immunosuppressed transplant patients is primarily due to virus reactivation. KSHV transmission, however, from an infected allograft can occur, and our study reports the first documented case of person-to-person transmission of KSHV.

Adult

EORTC classification for primary cutaneous lymphomas: a proposal from the Cutaneous Lymphoma Study Group of the European Organization for Research and Treatment of Cancer.

Primary cutaneous lymphomas represent a heterogeneous group of T- and B-cell lymphomas that show considerable variation in histology, phenotype, and prognosis. Recently, the European Organization for Research and Treatment of Cancer (EORTC) Cutaneous Lymphoma Project Group has reached consensus on a new classification for this group of diseases. The EORTC classification for primary cutaneous lymphomas is based on a combination of clinical, histologic, and immunophenotypic criteria, and thus contains well-defined disease entities rather than histologic subgroups. In addition, this new classification contains a number of provisional entities, which may display characteristic histologic features, but are not yet well defined clinically. These provisional entities account for less than 5% of all primary cutaneous lymphomas. In this report the basic principles of this new classification, as well as the characteristic features of the different disease entities, are described. In addition, survival data of 626 patients with primary cutaneous lymphomas derived from the registry of the Dutch Cutaneous Lymphoma Working Group, illustrating the clinical validity of this new classification, are presented.

Humans

Primary malignant mesothelioma of the tunica vaginalis of the testis. Immunohistochemistry and electron microscopy.

A case of primary malignant mesothelioma of the tunica vaginalis of the testis in a 75 year old man is here presented. Anamnesis for asbestos exposure was negative. Recurrent left hydrocele was the main symptom. Echography revealed a nodular mass in the caudal aspect of the epididymis and papillary projection on the surface of the tunica vaginalis of the testis. An inguinal left orchiectomy was performed. The tumor both in the solid area and in the papillary projections was identified as a malignant mesothelioma of epithelial type. The role of immunohistochemistry and ultrastructure for a correct definition of the tumor is underlined.

Aged

CD30-positive multilobated peripheral T-cell lymphoma primarily involving the subcutaneous tissue.

A 55-year-old woman presented with an inflammatory panniculitis-like plaque on her right thigh. Biopsy disclosed a subcutaneous infiltrate of multilobated T lymphocytes strongly expressing the CD30 antigen. A complete clinical remission was achieved with local radiation therapy, with no evidence of recurrence in 13 months of follow-up. To our knowledge, our patient is the first reported case of CD30-positive multilobated peripheral T-cell lymphoma primarily involving the subcutaneous tissue.

Female

CD56/neural cell adhesion molecule expression in primary extranodal Ki-1/CD30+ lymphoma. Report of a pediatric case with simultaneous cutaneous and bone localizations.

We describe the clinicopathologic features of an unusual case of CD30+/CD50+ T-cell lymphoma in a child who presented with simultaneous primary extranodal cutaneous and bone localizations. The expression of CD56 (neural cell adhesion molecule, or NCAM) is rare in non-Hodgkin's lymphomas other than in a group of haematopoietic/lymphoid neoplasms of natural killer and natural killer-like T-cells, which usually involve extranodal sites and often pursue an aggressive clinical behavior. Coexpression of CD30 and CD56 in T-cell lymphomas is exceedingly rare, and its biological significance is unknown. Our patient responded well to an intensive chemotherapy regimen, and she is now in complete remission 4 years after discontinuation of chemotherapy. Expression of NCAM could be regarded as responsible, in part, for the extranodal localization of lymphoma cells; expression of CD56 also might contribute to the definition of a subset of CD30+ lymphomas with distinctive clinicopathologic features.

Alkaline Phosphatase

Immunohistochemical study of skin lesions in acute and chronic graft versus host disease following bone marrow transplantation.

Allogeneic bone marrow transplantation (BMT) is the therapy of choice for a variety of malignant and nonmalignant disorders; however, a major constraint to successful BMT is graft versus host disease (GVHD). Skin lesions are the earliest presentation of GVHD. Donor-derived cytotoxic T lymphocytes are the effector cells responsible for lesions in the skin and other tissues. Here we show that most skin-infiltrating lymphocytes, in all forms of GVHD, are memory T cells with a predominance of CD4+ cells in the dermis and CD8+ cells in the epidermis. Relatively little attention has been focused on the adhesive phenotype of keratinocytes in GVHD. In this study, immunohistochemical analyses of skin biopsies from BMT patients with acute or chronic GVHD were conducted, with particular emphasis on antigen-presenting cells (APCs) and on keratinocytes. The distribution of APCs in the epidermis (Langerhans' cells) was investigated. Keratinocytes were analyzed for the expression of human leukocyte antigen DR locus (HLA-DR) and of a novel integrin, alpha10.1.2 beta1, which is detected in the basal layer of normal epidermis. Langerhans' cells were decreased in all grades of acute GVHD, but the epidermal APC network was reconstituted in chronic GVHD. HLA-DR was expressed by keratinocytes in grade 2 and 3 acute GVHD lesions, but not in two of three chronic GVHD cases, and in the regression phase of acute GVHD. Integrin chains alpha10.1.2 and beta1 were detected in the epidermal basal cell layer of most GVHD cases but they were also expressed in suprabasal keratinocytes of both acute and chronic GVHD. This latter finding indicates that a proliferative response uncoupled from differentiation occurs in keratinocytes in the course of GVHD.

Acute Disease

In situ expression of transforming growth factor beta is associated with melanoma progression and correlates with Ki67, HLA-DR and beta 3 integrin expression.

Transforming growth factor-beta (TGF beta), which is secreted by cultured melanoma cells constitutively, inhibits the proliferation of normal melanocytes and of most melanoma cells in vitro, but some melanoma cells from advanced stages of the disease develop resistance to TGF beta-dependent growth inhibition, without developing any change in TGF beta cell surface binding. In vitro TGF beta also downregulates the expression of HLA-DR molecules on melanoma cells, and upregulates the expression of the beta 3 integrin subunit on some cell lines. Immunohistochemical analysis of 53 melanocytic lesions (12 naevi, 30 primary melanomas and 11 metastases) revealed a trend of increasing expression of TGF beta and TGF beta receptor type III with tumour progression, and a significantly higher expression of both TGF beta (P < 0.0001) and the receptor (P < 0.05) in metastatic and thick (> 1 mm) primary melanomas compared with thin (< 1 mm) primary melanomas. The expression of TGF beta correlated with expression of a marker of proliferation, Ki67, and with HLA-DR and beta 3 integrin subunit expression. Coexpression of the four molecules was observed in all metastases and in most thick primary melanomas. These findings argue against an inhibitory effect of TGF beta on cell proliferation or HLA-DR antigen expression in melanoma, and suggest the upregulation of the beta 3 subunit. TGF beta protein appears to be a biological marker of melanoma progression in situ.

Adult

Fibrogenic cytokines in vulvar lichen sclerosus. An immunohistochemical study.

OBJECTIVE: To evaluate the expression of fibrogenic cytokines in lichen sclerosus (LS) infiltrate as compared with lichen planus (LP) infiltrate. STUDY DESIGN: Eight cases of vulvar LS (early stage, n = 3; well developed or old, n = 5) and 4 of vulvar LP were studied. Monoclonal antibodies directed against some of the major fibrogenic cytokines (IL-4, TGF-beta, IL-6) and against IFN-gamma, which inhibits collagen synthesis, were used per the alkaline phosphatase/anti-alkaline phosphatase technique on frozen sections. RESULTS: Staining for IL-4 revealed higher expression of fibrogenic cytokines (more than 50% infiltrating cells) in the LS infiltrate, mainly in early lesions, than in LP. Conversely, staining for IFN-gamma in LS was poor (less than 10% infiltrating cells), while strong positivity (more than 60% infiltrating cells) was found in LP. Staining for TGF-beta, a mediator of fibrosis in scleroderma, was similar in both LS and LP dermis. CONCLUSION: This study showed the immunohistochemical expression of fibrogenic cytokines in vulvar LS, with a different pattern as compared to that of LP. It is conceivable that dermal infiltrating cells actively participate, via cytokine production, in the pathogenesis of fibrosis in LS.

Adult

[The surgical treatment of a rare primary cardiac tumor: hemangioma. A report of 2 cases].

Primary benign tumors of the heart are particularly rare; cardiac hemangioma is one of the most rare primary benign cardiac tumors. Natural history, symptoms and prognosis of the disease depend on the potential complications due to the location and diffusion of the mass. We report on 2 cases of cardiac hemangioma, diagnosed occasionally in the first patient or due to gastroenteric symptoms in the second patient. The diagnosis was obtained by 2-D-echo and magnetic resonance imaging. In both cases the hemangioma was located on the right ventricle. Both patients underwent tumor resection in hypothermic cardiopulmonary bypass. In one case, a graft to the right coronary artery was associated; in the other case, the right ventricular outflow tract was reconstructed with an infundibular patch. Histology showed mixed hemangioma in one case and cavernous hemangioma in the other. The postoperative course was uneventful. At a follow-up of 8 years and 1 year, respectively, both patients are classified as NYHA 1 and both 2-D-echo and magnetic resonance imaging did not show any residual tumoral mass. This experience demonstrates that, depending on their location, benign neoplastic masses may be radically resected with acceptable operatory risks and excellent long-term results.

Aged

Unique digital skin lesions associated with systemic sclerosis.

A 40-year-old woman with systemic sclerosis presented with multiple, large soft skin lesions with a cystic appearance over the interphalangeal joints of both hands. Aspiration of one of these lesions revealed the presence of a yellowish mucoid material which rapidly reappeared. Surgical dissection and excision of the masses was followed by recurrence a few months later. Pre-operative diagnosis was that of myxoid cysts, but the histological picture was reminiscent of cutaneous focal mucinosis, another form of primary mucinosis. The origin of these unique skin lesions is unclear, but speculation on a possible aetiological relationship between them and systemic sclerosis is presented.

Adult