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Biomedical subjects

R Caputo

Publications and source records attributed to R Caputo.

At least 37 records · Page 2Linked to original sources
PubMed2000

Cutaneous infection caused by Serratia marcescens.

An 86-year-old woman presented with a chronic granulomatous skin lesion on the dorsal aspect of her left hand. Histologic examination showed pseudoepitheliomatous hyperplasia and a dense dermal infiltrate largely composed of lymphocytes and histiocytes. Abscess formation and fibroblastic proliferation were also present. Use of Fite, Giemsa, and periodic acid-Schiff stains did not show specific organisms. The gram-negative bacillus Serratia marcescens was the only microorganism isolated from all cultures performed. Trimethoprim-sulfamethoxazole, 960 mg every 12 hours for 20 days (orally), was given and resulted in complete disappearance of the lesion and negative culture findings. Cutaneous infection by S marcescens may represent a distinctive entity, whose clinical and possible pathogenic features are presented here.

Aged↗
PubMed1999

Lupus erythematosus with antiphospholipid syndrome and erythema multiforme-like lesions.

The occurrence of erythema multiforme (EM) in patients with lupus erythematosus (LE) has been described previously as a coincidental association. In contrast, LE with EM-like lesions and a peculiar immunological pattern, including positive rheumatoid factor, antinuclear antibodies and a serum antibody against an extract of human tissues recently recognized as similar to Ro (SSA), constitutes an established entity named Rowell's syndrome. We describe a woman with LE and long-standing widespread vesiculobullous and necrotic haemorrhagic EM-like lesions in combination with Ro (SSA) and scl-70 antibodies and the typical laboratory findings of the antiphospholipid syndrome (APS), namely lupus anticoagulant, anticardiolipin antibodies and prolonged activated partial thromboplastin time. This case could conceivably be consistent with a diagnosis of Rowell's syndrome, if the latter is regarded as a clinicopathological spectrum. However, the coexistence of LE, persistent EM-like disease and incomplete APS may also fulfil the diagnostic criteria for the 'multiple autoimmune syndromes'. We speculate that the laboratory markers of APS play a pivotal part in such an unusual clinical presentation.

Adult↗
PubMed1999

Evidence of retroviral involvement in an Italian patient with Ofuji's disease.

Ofuji's disease, also known as 'eosinophilic pustular folliculitis', is a rare inflammatory skin disorder of unknown aetiology, which affects mostly adult Japanese males. Only few Caucasian patients have been described so far. We report the case of a 44-year-old Italian woman with Ofuji's disease who had circulating antibodies against the recombinant envelope glycoprotein (Rgp46I) of HTLV-1. By means of a very sensitive nested PCR, the tax region of HTLV-1, but not other regions, was found in peripheral blood mononuclear cells. Our observations suggest that a retrovirus, closely related to HTLV but not yet identified, could be involved in the pathogenesis of the disease in this patient.

Adult↗
PubMed1999

Cooperative inhibitory effect of novel mixed backbone oligonucleotide targeting protein kinase A in combination with docetaxel and anti-epidermal growth factor-receptor antibody on human breast cancer cell growth.

Type I protein kinase A (PKAI) is overexpressed in the majority of human tumors and plays a relevant role in neoplastic transformation, conveying mitogenic signals of different growth factors and oncogenes. Inhibition of PKAI by antisense oligonucleotides targeting its RIalpha regulatory subunit results in cancer cell growth inhibition in vitro and in vivo. We have recently shown that a mixed backbone oligonucleotide targeting RIalpha can cooperatively inhibit human cancer cell growth when combined with selected cytotoxic drugs. In the present study, we have used HYB 165, a novel DNA/RNA hybrid mixed backbone oligonucleotide that exhibits improved pharmacokinetic and bioavailability properties in vivo and is presently undergoing Phase I trials. We have shown that HYB 165 exhibits a dose-dependent inhibitory effect on ZR-75-1 cells and a cooperative activity with docetaxel, a cytotoxic drug active in breast cancer. The antiproliferative activity is accompanied by increased apoptosis, as compared with each single agent. On the basis of our previous demonstration of a structural and functional relation between PKAI and epidermal growth factor receptor, we have performed a double blockade of these pathways using HYB 165 in combination with monoclonal antibody (MAb) C225, an anti-epidermal growth factor receptor chimeric MAb. The two compounds determined a cooperative growth inhibitory effect on ZR-75-1 cells and increased apoptosis. To study whether different biological agents and cytotoxic drugs can interact together, low doses of HYB 165, MAb C225, and docetaxel were combined causing an even greater cooperative effect toward growth inhibition. Finally, we have demonstrated that each single agent is able to induce bcl-2 phosphorylation and that the three agents, used in combination at suboptimal doses, determine a greater degree of bcl-2 phosphorylation and cause apoptosis of the majority of ZR-75-1 cells. These findings provide the basis for a novel strategy of treatment of breast cancer patients because both HYB 165 and MAb C225 are presently under clinical evaluation.

Antibodies, Monoclonal↗
PubMed1998

Cooperative inhibition of renal cancer growth by anti-epidermal growth factor receptor antibody and protein kinase A antisense oligonucleotide.

BACKGROUND: The expression of epidermal growth factor receptor (EGFR) and type I cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKAI) is associated with neoplastic transformation. By use of human renal cancer cell lines (i.e., 769-P, ACHN, A498, and SW839), we investigated the antiproliferative activity and the antitumor activity of an anti-EGFR humanized chimeric mouse monoclonal antibody, MAb C225, and a novel mixed backbone 18-mer antisense oligonucleotide, HYB 190, that targets expression of the RIalpha regulatory subunit of PKAI. METHODS: The antiproliferative activity of MAb C225 and oligonucleotide HYB 190, alone or in combination, on different renal cancer cell lines was determined by monitoring cell growth in soft agar. In addition, the induction of apoptosis by treatment with the anti-EGFR antibody and/or antisense PKAI oligonucleotides was evaluated by flow cytometric analysis of fragmented DNA. The antitumor activity of MAb C225 and oligonucleotide HYB 190 was determined in athymic mice bearing established ACHN tumor xenografts. Cell proliferation and tumor growth data were evaluated for statistical significance using Student's t test; reported P values are two-sided. RESULTS: MAb C225 and oligonucleotide HYB 190 inhibited colony formation in soft agar in a dose-dependent manner for all renal cancer cell lines tested. We observed a potentiation of growth inhibition and induction of apoptosis when 769-P cells and ACHN cells were treated with both agents. Combination treatment with MAb C225 and oligonucleotide HYB 190 caused regression of ACHN tumor xenografts, whereas single-agent treatment only delayed tumor growth. CONCLUSION: The combination of anti-EGFR MAb C225 and ited cooperative antiproliferative effects and cooperative antitumor effects on EGFR and PKAI-expressing human renal cancer cell lines.

Animals↗
PubMed1998

Localized peeling skin syndrome: case report with ultrastructural study.

We report a young woman in whom the history, clinical features, histopathological and ultrastructural findings led to a diagnosis of peeling skin syndrome (PSS). PSS is a rare and not well classified genodermatosis, mainly characterized by the spontaneous separation of the stratum corneum from the stratum granulosum. The unusual feature in our patient was the strict localization to the palm. PSS has been described as a more generalized disease frequently sparing palms and soles. We propose the diagnosis label of 'localized PSS' for this previously undescribed variant of a rare keratinization defect.

Adult↗
PubMed1998

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↗
PubMed1998

Gingival lesions in a patient with dermochondrocorneal dystrophy (François syndrome). A case report.

This report is concerned with gingival manifestations associated with a case of dermochondrocorneal dystrophy (DCCD) or François syndrome occurring in a 42-year-old woman. Our Department treated this patient for 15 years. Oral examination of this case revealed a diffuse enlargement and severe inflammation of the attached gingiva. Systemic findings were similar to those reported in the literature for patients with DCCD. Firm papules 3 mm wide, localized on the face and on the dorsal surface of the hands, were associated with corneal involvement and progressive and severe articular disorder. Because they recurred after surgical ablation, the gingival lesions became an important problem in the management of the patient. After 10 years of unsuccessful treatment limited to scaling, oral hygiene control and mouth rinses with 0.2% chlorexidine solution, the patient was submitted to extraction of the remaining teeth, remodelling osteoplasty and cutaneous graft. An acrylic full denture was inserted. In a follow-up of 7 years, good results for the oral health of the patient were seen.

Adult↗
PubMed1998

Uncommon clinical presentations of juvenile xanthogranuloma.

Two unusual clinical presentations of juvenile xanthogranuloma (JXG), the most common non-Langerhans cell histiocytosis, are described: a flat 'plaque-like' and a 'paired' form. This report confirms the great variability of JXG. Besides representing a dermatological curiosity, the recognition of these atypical forms of presentation should facilitate the clinical diagnosis of the disorder.

Diagnosis, Differential↗
PubMed1998

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↗
PubMed1997

Synergistic inhibition of human cancer cell growth by cytotoxic drugs and mixed backbone antisense oligonucleotide targeting protein kinase A.

Protein kinase A type I plays a key role in neoplastic transformation, conveying mitogenic signals of different growth factors and oncogenes. Inhibition of protein kinase A type I by antisense oligonucleotides targeting its RIalpha regulatory subunit results in cancer cell growth inhibition in vitro and in vivo. A novel mixed backbone oligonucleotide HYB 190 and its mismatched control HYB 239 were tested on soft agar growth of several human cancer cell types. HYB 190 demonstrated a dose-dependent inhibition of colony formation in all cell lines whereas the HYB 239 at the same doses caused a modest or no growth inhibition. A noninhibitory dose of each mixed backbone oligonucleotide was used in OVCAR-3 ovarian and GEO colon cancer cells to study whether any cooperative effect may occur between the antisense and a series of cytotoxic drugs acting by different mechanisms. Treatment with HYB 190 resulted in an additive growth inhibitory effect with several cytotoxic drugs when measured by soft agar colony formation. A synergistic growth inhibition, which correlated with increased apoptosis, was observed when HYB 190 was added to cancer cells treated with taxanes, platinum-based compounds, and topoisomerase II selective drugs. This synergistic effect was also observed in breast cancer cells and was obtained with other related drugs such as docetaxel and carboplatin. Combination of HYB 190 and paclitaxel resulted in an accumulation of cells in late S-G2 phases of cell cycle and marked induction of apoptosis. A cooperative effect of HYB 190 and paclitaxel was also obtained in vivo in nude mice bearing human GEO colon cancer xenografts. These results are the first report of a cooperative growth inhibitory effect obtained in a variety of human cancer cell lines by antisense mixed backbone oligonucleotide targeting protein kinase A type I-mediated mitogenic signals and specific cytotoxic drugs.

Animals↗
PubMed1997

Clinical efficacy and safety comparison of adapalene gel and tretinoin gel in the treatment of acne vulgaris: Europe and U.S. multicenter trials.

BACKGROUND: Adapalene is a new chemical entity that exhibits tretinoin-like activities in the terminal differentiation process. OBJECTIVE: We evaluated a dose range effect of two concentrations of adapalene gel as acne treatment and compared adapalene 0.1% gel with tretinoin 0.025% gel in the treatment of acne patients in two large multicenter studies. METHODS: Multicenter, investigator-masked, parallel group studies including 89 acne patients in the dose range study and 591 patients in the concurrent controlled studies were conducted. RESULTS: Adapalene gel 0.1% was significantly more effective in treating acne lesions than 0.03% adapalene gel. Adapalene gel 0.1% was significantly more effective than 0.025% or tretinoin gel in one study and of the same effectiveness in the other study. Adapalene gel was always better tolerated than tretinoin gel. CONCLUSION: Adapalene 0.1% gel is a safe and effective treatment of acne vulgaris.

Adapalene↗