Biomedical subjects
Publications and source records attributed to E Berti.
We report a case of prurigo nodularis of Hyde as the presenting sign of Hodgkin's disease in a 22-year-old girl. Though pruritus is a common symptom of Hodgkin's disease, prurigo nodularis has rarely been reported as a Hodgkin's symptom.
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Oral hairy leukoplakia was first described in homosexual men infected with the human immunodeficiency virus. It is thought to be caused by infection with both the Epstein-Barr virus and human papillomavirus. We report 59 cases of oral hairy leukoplakia. The disease was diagnosed in patients in all risk groups and was categorized in all classes of the Walter Reed classification without significant differences in prevalence. Epstein-Barr virus could be demonstrated in all tissue samples examined; human papillomavirus was found in only a few specimens. In our series oral hairy leukoplakia had a chronic course, although temporary spontaneous healing occurred in some cases. Its appearance was a poor prognostic sign because acquired immunodeficiency syndrome developed in a significant proportion of patients within a few months of onset.
Pityriasis lichenoides is usually classified into an acute and a chronic form. From a review of 89 cases of the disease seen since 1974 it seems that a more realistic classification into three main groups, according to the distribution of pityriasis lichenoides lesions, could be made, namely, a diffuse, a central, and a peripheral form, each characterized by a different clinical course. Conversely, no correlations were detected in our series between the severity of skin lesions and their distribution or the overall course of the disease. None of our cases suggests the possible evolution of pityriasis lichenoides into lymphomatoid papulosis. Although no infectious causative agent has been identified, a viral origin seems likely in some cases. Most patients responded favorably to UVB irradiation. Our conclusions are (1) that pityriasis lichenoides is probably a clinical disorder with a diverse etiology and (2) that its classification by distribution seems more useful than its subdivision into an acute and a chronic form.
A panel of 19 melanoma clones was characterized by fluorescence activated cell sorter analysis for the expression of distinct integrin receptors in the very late activation antibody subfamily. A group of five melanoma clones (2/4, 2/14, 2/17, 2/51, and 2/60) was identified that shared coordinate expression of multiple VLA antigens. These same clones were more susceptible, in terms of lytic units, to cell-mediated lysis and also expressed the lower melanin content per cell in the panel. The data suggest that in a heterogeneous neoplastic population, distinct features such as susceptibility to cell-mediated lysis and expression of receptors for extracellular components are variables preferentially associated with cells in an early stage of differentiation.
Recently, monoclonal antibodies (MoAb) have been raised against a family of adhesive membrane receptors (R) for extracellular matrix molecules known as integrins. In order to ascertain whether these adhesive proteins are normally expressed in inherited epidermolysis bullosa (EB) dermal epidermal junction, we studied the reactivity of MoAb recognizing receptors for VLA-1 (R for unknown ligand), VLA-2 (R for collagen), VLA-3 (R for collagen, laminin, fibronectin), VLA-4 (R for unknown ligand), VLA-5 (R for fibronectin), VLA-6 (R for laminin), VNR alpha, and VNR beta (R for vitronectin) on cryostat skin sections from EB patients and normal controls and on cytospins of normal epidermal cell suspensions with indirect immunohistochemical methods. Two cases of junctional EB (EBj) (lethal and non-lethal), three cases of dominant dystrophic EB (EBdd), two cases of recessive dystrophic EB (EBdr), and two normal controls skin sections and cell suspensions entered the study. No significant modification of the distribution of these adhesive receptors was observed in junctional and dystrophic EB skin. Both in normal and EB specimens MoAb against VLA-2, VLA-3, and VNR alpha determinants showed reactivity with the total cytoplasmic membrane of basal keratinocytes and basement membrane zone. Interestingly, anti-VLA-6 MoAb was characterized by an intense linear staining of the dermal-epidermal junction with the same localization on the roof of the blisters in EBj, EBdd, and EBdr as bullous pemphigoid (BP) serum. On the basis of these results we suggest that anti-VLA-6 MoAb could be used instead of BP serum for immunohistochemical detection of the cleavage of blisters in EB.
Prenatal diagnosis of junctional epidermolysis bullosa associated with pyloric atresia was carried out in a couple at risk. Their two previous children had died during the first months of life of the same disorder despite surgery for the pyloric abnormality. Ultrastructural study of fetal skin biopsies obtained at 18 weeks' gestation showed dermal-epidermal separation at the lamina lucida level, while ultrasound showed marked stomach dilatation. Light microscopy of pyloric tissue obtained after termination showed the pyloric lumen to be replaced by loose connective tissue with no inflammatory reaction. Immunofluorescence studies on the skin specimens with the monoclonal antibody GB3, known to be absent in 'lethal' junctional epidermolysis bullosa skin, disclosed a marked positivity suggesting that the junctional epidermolysis bullosa in this case may be of the 'non-lethal' type.
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Fourteen cases of primary cutaneous B-cell lymphomas were investigated at the immunohistochemical and molecular level to further characterize this newly defined entity. Neoplastic cells from all cases, phenotyped with a panel of monoclonal antibodies, were positive for HLA-DR, for the B-cell markers CD19, CD22, but not CD23 (except one case), and negative for the T-cell marker CD2. Monoclonal immunoglobulin light chains were demonstrated in six cases. The reactivity with the Ki-67 monoclonal antibody indicated that the neoplastic cells are proliferating. In five biopsies the presence of dendritic cells infiltrating the neoplastic areas was revealed using the monoclonal antibody Kim4b. By Southern blot analysis, clonal rearrangement of the immunoglobulin heavy chain gene (involving one or both alleles) was shown in 12 of 14 cases and of the light chain genes in 13 cases. The bcl-2 oncogene, normally involved in nodal follicular lymphomas, was in germ-line configuration. The c-myc and the beta and gamma chain genes of the T-cell receptor were also in the germ-line configuration. None of the cases presented Epstein-Barr virus sequences. These data indicate that primary cutaneous lymphomas of B-cell origin share morphological and phenotypic similarities with the nodal B-cell lymphomas of follicular histotype, are proliferating, and express in 45% of cases clear monoclonal immunoglobulin light chain; the molecular analysis confirms the B-cell derivation and the monoclonal nature of this neoplasia; it also shows that neither bcl-2 nor c-myc oncogenes are involved and that no inappropriate rearrangements of the T-cell receptor genes are found in this lymphoma.
Bone marrow cells of a patient with Letterer-Siwe disease were cultured for three weeks in long-term bone marrow culture (LTBMC) conditions and examined at one-week intervals with a large panel of monoclonal antibodies by immunohistochemistry and by the immunogold transmission electron microscopy (immunoTEM) technique. Although at diagnosis the bone marrow showed a slight increase of monocytes with a normal phenotype, a rapid expansion of cells expressing CD1a and CD1c was observed already after 1 week of culture. A progressive increase in CD4, CD11b and CD11c expression was also observed. ImmunoTEM of cultured cells demonstrated that CD1a+ cells had macrophage-like morphology, and did not contain Birbeck granules. These findings indicate that bone marrow monocytes acquire some phenotypical features of Langerhans cells in LTBMC and support the hypothesis that these cells may derive directly from a bone marrow monocytic precursor.
Anaplastic large cell lymphoma is a subtype of nodal and extranodal lymphoproliferative disorder characterized by peculiar histopathological features and the positivity of lymphoid proliferating cells for Ki-1/Ber-H2 monoclonal antibody. A case, misdiagnosed as cutaneous metastasis and treated by surgery, in a woman with a history of previous neoplasms, is reported. In spite of the histopathological malignancy of the tumor, the patient is alive and free from recurrent or metastatic disease after 3 years of follow-up.
We studied complement (C') involvement in paediatric coeliac disease (CD) and dermatitis herpetiformis (DH) in relation to lesions and function of enteric mucosa and to diet. For this purpose, 50 children affected by CD and 42 affected by DH were subdivided in 3 groups: in the first (I) were included subjects in free diet, in the second (II) children during gluten-free diet (GFD) and in the third (III) subjects after gluten reintroduction in diet. Only in CD we found significant modifications of some C' parameters. In fact C3 and C4 levels increase in II group in GFD (respectively p less than 0.02 and p less than 0.03) and result inversely correlated to an arbitrary score for the evaluation of the enteric histological lesions (p less than 0.02 and p less than 0.01). C3d/C3 ratio levels, as catabolic index of C3, result always greater than normal in both diseases, but significantly decrease only in II group of CD children (p less than 0.02), where they result also positively correlated to the histological score (p less than 0.05). Circulating immune complex-like material is higher in DH, but incidence of pathological values decrease in II group only in CD (p less than 0.04). These data suggest probable significant differences in the pathogenetic mechanisms of CD and DH involving C'.
Activity of p53, H-ras, c-myc and c-fos in psoriatic lesions was studied using monoclonal antibodies (MoAbs) performing a sensitive immunohistochemical method on frozen sections. Normal skin from surgery was used as control. Reactivity of p53, H-ras and c-myc is remarkable in psoriatic plaques but, in contrast, c-fos expression does not show differences compared to control skin. These findings led us to speculate about the importance of cellular oncogenes in the pathogenesis of psoriasis.
A considerable intensification of the avidin-biotin-peroxidase complex staining system (ABC) was obtained by sequentially overlaying the sections to be immunostained with an avidin-rich and a biotin-rich complex. Each sequential addition contributed to the deposition of horseradish peroxidase on the immunostained site and allowed the subsequent binding of a complementary complex. With this technique a higher dilution of the antisera could be used and minute amounts of antigen masked by the fixative could be demonstrated on paraffin sections.
To clarify the nature of reticulohistiocytoma of the dorsum, 19 cases, including three of the seven original cases described by Crosti, were evaluated clinically, histologically, and immunologically. In seven cases gene rearrangement analysis was also performed. Results indicate that reticulohistiocytoma of the dorsum must be considered a primary cutaneous B cell lymphoma of follicular center cell origin. This localized skin disease has a very slowly progressive course, with many patients showing no systemic involvement even after prolonged follow-up.
Cutaneous histiocytosis was discovered in a 40-year-old man with a slow-growing nodule located on his right arm. Histologic findings showed an epidermotropic infiltrate of histiocytes with folded, irregular nuclei. Immunologically, the cells presented an intermediate phenotype between Langerhans' cells and dermal macrophages. After surgical removal of the lesion, neither a relapse nor visceral involvement was observed during two years of follow-up.
The labelling pattern of eight lectins was studied in jejunal samples from ten normal subjects, in order to define the normal distribution of structural and secretory glycoconjugates in the small bowel. The following lectins were studied by means of a peroxidase technique on formalin-fixed samples: Arachis hypogaea, Ricinus communis, Canavalia ensiformis, Lens culinaris, Phaseolus vulgaris, Triticum vulgaris, Ulex europaeus, Dolichos biflorus. Phaseolus vulgaris reacted with goblet cell mucus throughout the villus-crypt axis. Conversely Ulex europaeus, Dolichos biflorus and Triticum vulgaris lectin labelling of goblet cells appeared to be confined to the upper part of the villi. This finding suggests that during cell migration from crypt to villus tip, the continuing maturation of goblet cells is associated with the differentiation of secretory carbohydrates, which probably parallels the cell maturation cycle. Lectin histochemistry appears to be a reliable tool for the study of structural and secretory glycoconjugates in the jejunal mucosa, and might be of value in the study of diseases in which the cell-maturation cycle in the small bowel is altered.
Bone marrow biopsies from 7 patients afflicted with hairy cell leukemia were studied with a panel of monoclonal antibodies at different intervals during alpha recombinant interferon therapy. Monoclonal antibodies Dako-LC and F 8.11.13 were used because they are highly reactive with hairy cells, and 82H3 and LeuM 1 were also utilized to identify respectively the residual hemopoietic and myeloid tissue. All antibodies are reactive on sections of formalin-fixed, paraffin-embedded biopsy material. Before therapy a uniform hairy cell infiltrate was present and very little tissue was visible even after immunohistochemical staining. During therapy, identification of hairy cells in routine biopsies was difficult, since they were mixed with normal cells and the bone marrow was generally hypoplastic. Immunohistochemical stains seem to allow better identification of hairy cells and a more precise estimate of the degree of repopulation by normal bone marrow cells. It was evident, especially after immunocytochemical analysis, that interferon drastically reduced the extent of the infiltrate and allowed recovery of normal hemopoiesis, but did not produce complete remissions.