Search PubMed⌕ Search

Biomedical subjects

A Cerri

Publications and source records attributed to A Cerri.

At least 109 records · Page 6Linked to original sources

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↗

Synthesis, cardiotonic activity, and structure-activity relationships of 17 beta-guanylhydrazone derivatives of 5 beta-androstane-3 beta, 14 beta-diol acting on the Na+,K(+)-ATPase receptor.

A series of digitalis-like compounds, with the lactone ring shifted from the original position through a spacer or replaced by a series of guanylhydrazone substituent-bearing chains, was synthesized and evaluated for inhibition of Na+,K(+)-ATPase and for inotropic activity. The highest Na+,K(+)-ATPase inhibition (IC50) and inotropic activity (EC50) were reached with the vinylogous guanylhydrazone 5 where a cardenolide-like polarized alpha,beta-unsaturated system and a basic guanidino group were both present at the 17 beta-position; for this compound IC50 and EC50 values were comparable to or higher than those of Thomas' parent guanylhydrazone 1, digitoxigenin, and digoxin. A substantial improvement of the desired positive inotropic activity versus the toxic arrhythmogenic concentration was not reached within this series; only a slightly better therapeutic index can be envisaged for compounds 5 and 4, even though, for the latter, to the detriment of potency, presumably because of a weaker interaction with the receptor, due to the lack of a cardenolide-like polarized system.

Androstanes↗

[Adenoid cystic cribriform trichoblastoma].

In hair germ tumors, hair follicle development is partially or completely recapitulated. The trichoblastoma represents a purely epithelial tumour within this group of tumours. We identified a trichoblastoma showing exclusively adenocystic features in a 32 years old woman. This variant has been very rarely described in the literature. We review the history of hair germ tumors and discuss the problems of their classification.

Adult↗

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↗

Regional eruptive neurofibromas.

A 71-year-old woman presented with multiple, flesh-colored, papular lesions on the left dorsal side of the hand which had erupted 5 years earlier. No cafè-au-lait spots, freckles, or Lisch nodules were detected. Family history did not disclose neurofibromas or abnormal pigmentation. Two biopsy specimens of the lesions showed circumscribed, non-encapsulated neurofibromas. Segmental neurofibromatosis is characterized by the unilateral, segmental appearance of neurofibromas and/or cafè-au-lait spots in the absence of genetic transmission. The authors discuss the significance of localized multiple cutaneous neurofibromas in the absence of family history and suggest the possibility of a cutaneous hamartoma.

Aged↗

Unusual clinical features of fingernail infection by Fusarium oxysporum.

Four cases of invasion of fingernails caused by Fusarium oxysporum are described. The typical picture of onychomycosis by this non-dermatophytic mould is a 'white superficial onychomycosis' which usually affects the great toenail. Only few cases of fingernail infections by this organism have been described in the literature and, to our knowledge, there are no reported cases on the pustulous and eczema-like aspect of paronychia by Fusarium oxysporum. We report different and unusual clinical features of this infection successfully treated with systemic antifungals. Two patients were treated with terbinafine, 250 mg daily for 3 months, and two patients with itraconazole, 200 mg daily for 3 months.

Adult↗

Ungual phaeohyphomycosis caused by Alternaria alternata.

Phaeohyphomycoses are a heterogeneous group of rare mycotic infections caused by dematiaceous fungi. They are classified into four forms: superficial, cutaneous and corneal, subcutaneous, systemic. Alternaria species are ubiquitous fungi that are occasionally aetiological agents of pheohyphomycosis. A case of onychomycosis caused by Alternaria alternata treated with itraconazole is reported.

Aged↗

Synthesis and quantitative structure-activity relationship of 17 beta-(hydrazonomethyl)-5 beta-androstane-3 beta,14 beta-diol derivatives that bind to Na+,K(+)-ATPase receptor.

A series of 17 beta-(hydrazonomethyl)-5 beta-androstane-3, beta,14 beta-diol derivatives was synthesized and evaluated in the displacement of [3H]ouabain binding from Na+,K(+)-ATPase. The data were explored with multiple linear regression and partial least-squares to find possible quantitatives structure-activity relationships. Good correlations were found between binding to the receptor and van der Waals volumes or molar refractivities of the 17 beta-hydrazonomethyl substituents and pKa values of the compounds. Equivalent results were obtained using the proton affinity (calculated using MOPAC) of the hydrazone residues instead of experimental pKa. As basicity or related electronic factors of the substituents explain a significant portion of the observed changes in the activity, an ion-pair interaction between a carboxylate residue of the enzyme and the protonated 17 beta-hydrazonomethyl group, as postulated by Thomas, plays an important role in the interaction of the ligand to the Na+,K(+)-ATPase receptor.

Androstane-3,17-diol↗

Immunohistochemical localization of a novel beta 1 integrin in normal and pathologic squamous epithelia.

The 10.1.2 MoAb reacts with a novel alpha chain that associates with the beta 1 integrin chain and is widely distributed among epithelial and endothelial cells of human adult and fetal tissues. In the epidermis and in other squamous epithelia, alpha 10.1.2 chains are expressed exclusively in the basal cell layer. Here we describe the immunohistochemical localization of alpha 10.1.2 in human epidermis, in other squamous epithelia, as well as in cultured keratinocytes. alpha 10.1.2 chain localization has also been investigated in a variety of non-neoplastic and neoplastic lesions of the skin, the uterine cervix, and the lung. We show that alpha 10.1.2 chains retain their basal keratinocyte localization in hyperplastic skin diseases and in benign tumors of the epidermis and that they are strongly expressed in basal cell carcinomas. In contrast, alpha 10.1.2 expression is decreased in keratinocytes that differentiate in vitro and is lost in epidermal dysplastic conditions, in the invading front of squamous cell carcinomas of the epidermis, in microinvasive cervical cancers, and in well-differentiated squamous lung tumors. These findings indicate that alpha 10.1.2 beta 1 integrin is downregulated during keratinocyte differentiation in vitro and in vivo. Moreover, lack of alpha 10.1.2 expression in basal cells of squamous epithelia is associated with early dysplastic changes and with the acquisition of invasive capacity.

Antibodies, Monoclonal↗

[In vitro effects of IL-2 on human hypophyseal adenoma].

The effects of two different concentrations of IL-2 on human pituitary adenomas (one secreting ACTH and one secreting GH) were evaluated in vitro. A specimen of the tumor was dissagregated and the cells were incubated for three days with RPMI 1640 medium. The medium was then decanted and the cells were incubated with 1 mlo of fresh medium for three hours and then with new fresh medium containing two different concentrations of IL-2, 100U/ml, for three hours too. The pituitary hormones, ACTH and GH, released into the medium were assayed by RIA. Dose of 100 U IL-2 induced a profound increase of ACTH release. The other dose decreased ACTH release. The release of GH was suppressed by IL-2 at the two concentrations tested. IL-2 may be an immunologic messenger exerting direct action at pituitary level. It appears probable that IL-2 plays an important role in determining the response of the pituitary to stress and infections.

Adenoma↗

Synthesis and pharmacological activity of a series of dihydro-1H-pyrrolo[1,2-a]imidazole-2,5(3H,6H)-diones, a novel class of potent cognition enhancers.

A series of dihydro-1H-pyrrolo[1,2-a]imidazole-2,5(3H,6H)-diones were synthesized. These bicylic derivatives contain both the 2-pyrrolidinone and 4-imidazolidinone nuclei, already recognized as important for cognition enhancing activity. In addition, these structures maintain the backbone of piracetam and oxiracetam with the acetamide side chain restricted in a folded conformation. Their ability to reverse scopolamine-induced amnesia was assessed in a one trial, step-through, passive avoidance paradigm. The main features observed are a potent antiamnestic activity after ip administration (minimal effective dose being between 0.3 and 1 mg/kg ip for most compounds), the presence of a bell-shaped dose-response curve and, generally, a reduction of biological activity after po administration. However, the unsubstituted compound (15, dimiracetam) shows no evidence of a bell-shaped dose-response curve and completely retains activity when given orally, being 10-30 times more potent than the reference drug oxiracetam.

Amnesia↗

[Hashimoto's thyroiditis and HLA in Caucasian Italians].

Sixty cases of goitrous Hashimoto's thyroiditis were observed at the first diagnosis. For 18 of the cases, the diagnosis was made only on the basis of cytological examination since antithyroid antibodies were always negative. To determine if seronegative or seropositive forms constituted a particular genetically determined subgroup, we evaluated whether such peculiarities were related to specific HLA haplotype. Analysis of HLA antigens showed in the seropositive a significant increase in the frequency of HLA-B51 and HLA-A2, a significant decrease in the frequency of HLA-A1 and HLA-DR1. In seronegative cases no increase was found in the frequency of HLA-A-B-DR antigens, but they showed a strong positive association with HLA-DQ3. Our results show that association of Hashimoto's thyroiditis with HLA antigens was different in seronegative and seropositive subgroup. This finding would seem to support the hypothesis that in a few subjects the entire immune process develops exclusively within the involved organ and this process would be genetically determined.

Adult↗

Increased jejunal intraepithelial lymphocytes bearing gamma/delta T-cell receptor in dermatitis herpetiformis.

T-cell receptor 1 (gamma/delta) expression was studied in 19 jejunal or duodenal specimens from patients with dermatitis herpetiformis and in 16 jejunal or duodenal specimens showing normal histology. In normal specimens, gamma/delta+ cells represented 10.8% of intraepithelial CD3+ lymphocytes. Around 50% of these cells were recognized by the A13 monoclonal antibody, which detects products of the V gamma 1/V delta 1 gene rearrangement and the non-disulfide-linked form of T-cell receptor 1. The remaining 50% reacted with the BB3 monoclonal antibody, which recognizes products of the V gamma 9/V delta 2 rearrangement and the disulfide-linked form of receptor. Very few gamma/delta+ cells were observed in the lamina propria. In jejunal specimens from patients with dermatitis herpetiformis, a significant increase in the prevalence of gamma/delta+ intraepithelial lymphocytes was observed (P less than 0.001). This finding was largely accounted for by an increase in those cells recognized by the A13 monoclonal antibody, thus possibly expressing the V gamma 1/V delta 1 rearrangement and the nondisulfide-linked form of receptor. These data suggest that similar pathogenetic mechanisms may be active in determining the jejunal damage in celiac disease and dermatitis herpetiformis.

Animals↗

Expression of the alpha 6 beta 4 integrin in lesional skin differentiates bullous pemphigoid (BP) from epidermolysis bullosa acquisita (EBA).

The integrin alpha 6 beta 4 complex is a protein of the membrane of basal keratinocytes, localized at the surface of cells in contact with the basement membrane zone in normal skin. The expression of alpha 6 beta 4 was investigated in several autoimmune blistering skin diseases including bullous pemphigoid (BP), epidermolysis bullosa acquisita (EBA), bullous systemic lupus erythematosus (BSLE), and pemphigus vulgaris (PV) by an indirect immunofluorescence technique. In lesional bullous skin of BP, alpha 6 beta 4 expression was either absent, or in some cases represented an unusual irregular patchy staining. In contrast, in lesional bullous skin from EBA, BSLE, and PV, alpha 6 beta 4 expression was comparable to that observed in normal skin, i.e., a linear staining of the BMZ. Thus, analysis of the alpha 6 beta 4 integrin reactivity on lesional skin, in conjunction with the typical localization of collagen IV, allows a rapid and accurate distinction between BP and EBA.

Diagnosis, Differential↗

Human melanoma metastasis culture supernatant contains chemotactic factors for phagocytes.

Several findings point out that melanoma culture supernatants release soluble factors which modulate mononuclear cell chemotactic responsiveness. In this regard, either an enhancement or an impairment of chemotactic capacity has been found. Here, we provide evidence that supernatant recovered from human melanoma cell metastasis culture is able to trigger monocyte and polymorphonuclear cell chemotaxis. This activity is not affected by the presence of anti-IL-1 antibody during the assay. Further studies are in progress to isolate and characterize soluble factors involved in this activity.

Chemotactic Factors↗

Familial prevalence and coaggregation of schizotypy indicators: a multitrait family study.

Schizophrenic probands (n = 17), their first-degree relatives (n = 61), and medically and psychiatrically screened normal control subjects (n = 18) were studied with structured interviews for DSM-III Axis I disorders and schizotypal personality disorder, questionnaire measures of schizotypy, measures of smooth-pursuit eye movement dysfunction, and attention dysfunction. Schizophrenic subjects scored abnormally on essentially all measures. Relatives differed significantly from control subjects on most measures. Correlational analyses indicate that many characteristics tested in these measures run together in families. The data are consistent with the hypothesis that a single vulnerability dimension or typology, presumably in part genetically transmitted, may account for phenotypically distinct abnormalities. These traits, taken together, may have joint usefulness for identifying persons with a predisposition to schizophrenia.

Adult↗

Primary cutaneous gamma/delta T-cell lymphoma presenting as disseminated pagetoid reticulosis.

The first case of primary gamma/delta cutaneous T-cell lymphoma (CTCL) with a fatal outcome is reported. The patient had the clinical and histopathologic features of disseminated pagetoid reticulosis, a rare form of CTCL characterized by a strong epidermotropic lymphoid infiltrate. Extensive immuno-cytochemical studies showed that the neoplastic cells were almost exclusively localized in the epidermis, expressed the gamma/delta variant of the T-cell receptor (CD3+, TCR-delta-1+) and were CD5+, CD7+, CD27+, CD29+, CD43+, CD44+, CD45+, CD45RA+, CD54+, CD69+, but beta F1-, Ti gamma a-, BB3-, A13-, CD2-, CD4-, CD8-, CD11a-, CD49d-, CD25-, CD30-, and HLA-DR-. A comparison of our results with those of the literature, which have not included gamma/delta T-cell receptor analysis, suggests that some reported cases of pagetoid reticulosis may have phenotypes similar to our case. Electron microscopy studies demonstrated that the gamma/delta T lymphocytes were villous, containing dense and multivesicular bodies, and formed close contacts with the surrounding keratinocytes, suggesting that these cells should have a role in the skin-associated lymphoid tissue. The proliferating cells in our case might represent the neoplastic counterpart of the recently reported CD2- subset of normal human peripheral blood gamma/delta T lymphocytes.

Aged↗