1,721,024 research outputs found

    Treatment of refractory pemphigus with the anti-CD20 monoclonal antibody (Rituximab)

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    Pemphigus is a severe blistering disorder caused by autoantibodies to desmogleins 1 and 3. Because some patients with pemphigus never enter into remission, new immunosuppressants are warranted. Rituximab is a chimeric monoclonal antibody binding to the CD20 antigen on B cells, which proved to be effective in recalcitrant pemphigus. OBJECTIVES: To evaluate the efficacy and safety of rituximab in refractory pemphigus and to investigate its effects on the autoantibody profile. PATIENTS AND METHODS: Six patients with recalcitrant pemphigus were treated. Rituximab was administered intravenously at a dosage of 375 mg/m2 body surface once weekly for 4 weeks. RESULTS: Three pemphigus foliaceus patients and 1 with mucocutaneous pemphigus vulgaris (PV) showed complete response over a follow-up period of up to 18 months. In one oral PV, control of the disease was achieved using pulse therapy with cyclophosphamide following rituximab withdrawal. In one PV with vegetating features, good improvement was obtained after 6 rituximab infusions. All patients tolerated the treatment well. Anti-desmoglein autoantibodies significantly decreased only in pemphigus foliaceus. CONCLUSIONS: This study highlights that rituximab is a valuable drug for refractory pemphigus, although the response of mucous membranes and cutaneous folds may be delaye

    The usefulness of clonality for the detection of cases clinically and/or histopathologically not recognized as cutaneous T-cell lymphoma

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    The determination of clonality has proven to be a useful adjunct to the diagnosis of cutaneous lymphocytic infiltrates. It is considered particularly helpful for the distinction of mycosis fungoides (MF) and inflammatory dermatoses. OBJECTIVES: To verify the sensitivity of the polymerase chain reaction (PCR)-heteroduplex analysis of T-cell receptor gamma-chain gene (TCRgamma) rearrangements in patients with MF and to establish whether a clinicopathological re-evaluation of lesions previously unclassified or considered to be non-neoplastic entities but found to be monoclonal allowed the recognition of additional cases of MF. METHODS: Included in the study were 116 patients, seen at our Institute from April 2002 to September 2003 and tested for TCRgamma rearrangements. Thirty-six patients were affected by clinically and histopathologically proven MF, while the remaining 80 cases had not been classified or had been classified as non-neoplastic entities. The sensitivity of the molecular analysis was determined on the basis of the results obtained in the 36 patients with MF. The 29 cases of the second series of patients found to be monoclonal were clinically and histopathologically re-evaluated. RESULTS: Clonal rearrangements were found in 87.5% of patients with plaque stage MF and in 20% of those with patch stage MF. The clinicopathological re-evaluation allowed us to reclassify 15 of 29 monoclonal cases of the second series of patients as MF. CONCLUSIONS: The study showed that the PCR-heteroduplex technique can determine a high percentage of monoclonality only in plaque stage MF. However, in spite of the low sensitivity of the method, several cases previously unrecognized could be reclassified as MF when their clinical and histopathological features were re-evaluated taking into account the clonality of the lymphocytic infiltrate

    Cytokeratin profile in basal cell carcinoma

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    Origin of basal cell carcinoma (BCC) is still unclear. We studied the cytokeratin (CK) profile in BCC using monoclonal antibodies against 12 CKs to further investigate the suggested origin of the tumor from follicular matrix cells or from follicular outer root sheath cells and to determine if BCC subtypes can be identified on the basis of their CK profiles. Cases of pilomatricoma and samples of fetal skin served as controls to establish the CK profile in matrical cells and developing follicles during intrauterine life, that of the epidermis and cutaneous adnexa in adult life having been determined in a previous study. The most significant findings were as follows: (a) CK 5 and CK 17 positivity in all the BCCs studied; (b) CK 7, CK 8, CK 18, and CK 19 positivity in 30/52, 33/52, 42/52, and 14/52 BCCs, respectively; (c) CK 14 negativity in almost all the BCCs studied; and (d) lack of CK 1 expression only in 2/2 morpheiform BCCs and 4/10 nodular BCCs. The study suggests a tumorous differentiation toward follicular outer root sheath cells and, in most cases, also toward the glandular components of the pilosebaceous-apocrine unit. No significant difference in the CK profile among the BCC subtypes studied was foun

    Primary cutaneous T-cell lymphoma expressing FOXP3: a case report supporting the existence of malignancies of regulatory T cells

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    Regulatory T (Treg) cells, which represent 5% to 10% of peripheral T cells, regulate the activities of T-cell subsets by performing immunosuppressive functions and thus preventing the development of autoimmune responses. The majority of Treg cells are CD4+, CD25+, and FOXP3+. Recently, it has been demonstrated that the tumor cells in adult T-cell leukemia lymphomas can function as Treg, raising the question of whether any variant of primary cutaneous T-cell lymphoma may also express a regulatory phenotype. We describe an extraordinary case of primary cutaneous T-cell lymphoma clinically characterized by protean cutaneous manifestations and histologically showing a pattern consistent with epidermotropic pleomorphic medium-/large-cell primary cutaneous T-cell lymphoma. The majority of neoplastic cells were CD4+ CD25+ T cells and strongly expressed FOXP3. With this background, the current case, characterized by an aggressive course requiring polychemotherapy, may support the existence of lymphoproliferative malignancies of Treg cells

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    New monoclonal antibodies (mAbs) of the 9th HLDA Workshop: an immunohistochemical analysis of the FACS and IHC panel mAbs on normal and activated skin and tonsil

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    Cross reactivity and multiple reactivities are very frequently detected in tissue studies; this study summarize the pattern of tissue staining of normal and pathological skin (affected from cutaneous lymphomas) and normal tonsil observed by using FACS and IHC panels of the 9th HLDA Workshop. FACS panel: cryostat sections of frozen tissues were dried for 12 hours, fixed 10" in aceton and stained by an avidin-biotin immunoalkaline phosphatase method (DAKO). IHC panel: formalin fixed paraffin-embedded sections were dewaxed, heated in EDTA buffer (PH-8) for 15 min in a pressure cooker and immunostained by an avidin-biotin immunoalkaline-phosphatase method (DAKO). A) Skin reactivity results: N° 7 (FcRLB) and N°8 (CD20L) labelled epithelial cells (EP) and polymophonuclear leucocytes (PMN); N° 16 (XBP-1s) smooth muscle (SM), EP, dendritic cells (DR) and melanocytes (MEL); N° 18 DC, SM and EP; N° 20/21 (FCRL1-2) EP, collagen fibers (COLL) and nerves (N); N° 24 EP, COLL fibers, macrophages (MO) and fibroblasts (Fb); N° 26 (SC3) hair and eccrine gland (ADN); N° 30(CD210) EP; N° 32(CDW329) DR, MO, EP; N° 33 DC, EP and ADN; N° 34 MO, EP and AND; N° 35 MO; N° 39 (CD124) EP; N° 40(CD200) vessels (Vs) and ADN; N° 41(CD130) Vs and EP; N° 48(CD196) EP and ADN; 49(CD267) ADN; N° 52(CD191) EP and AND; 53(Int.beta5) and 54 (CD320) Vs, EP, AND, Fb; N° 55(DR4), N° 56(CMKLR1) EP and AND; N° 57(DR5) MO, Fb, EP, and AND; N° 58(Notch-1) Vs, EP and AND; N° 59 (4IgB7-H3) EP, Vs, striated muscle; N° 74(Int.beta6) EP and AND; N° 75(Dectin-1) Vs, EP and AND; N° 76-101(TREM-1) Vs, EP, MO and PMN; N° 77(Siglec-5/14) PMN and MO; N° 78(AMICA) Epand AND; N° 80(Siglec-9) MO, DR and PMN; N° 82(int.alfaVbeta5) MO, DR, EP, COLL, Fb, Vs; N° 84(DCIR) PMN; N° 85/99(GITR) PMN, EP and AND; N° 86(CD229) MO; N° 87(CD319) MO and plasmocytes (PC); N° 88(CD48) MO, DR and EP; N° 84(CD84) MO, DR and basal membrane (BM); N° 93(NTBA) MO, DR and PC; N° 94(HVEM) MO, Vs and EP; N° 95(TSLPR) nerves (Nv), EP and ADN; N° 98 (Galectin-3/Mac-2) MO, PMN, TBM, VS,COLL and EP; N° 100(Lymphotoxin betaR) EP; N° 106(CD150) MO-DR; N° 115(BLK 10B/2) Vs; N° 116(Bclx/8H) SM, EP, ADN, COLL, Fb; N° 128(CD38) EP; N° 223(AID) EP, ADN and MEL; N° 263(EVI2) MO and PC. B) Tonsil reactivity with mononuclear cells and resident cells were detected in all mAbs, also if some reagents showed in our method high background (n° 6, 16, 17, 19, 24, 26, 27, 59, 69, 72, 81, 115, 116) or weak staining (n° 7, 8, 9, 10, 29, 32, 62, 67, 71, 78, 90, 91, 92). Results: N° 11(TRAIL-R2/DR5), 223 (AID), 263 (EVI2b) and 268 (LSP1) showed a pan leukocyte reaction; interestingly BLIMP1 specific N° 6/19 showed a cytoplasmic wide reactivity with FOL, PC, MO and T cell areas, whereas N°103/105 showed a strong nuclear staining of the PC and of the EP cells; N°13/107(BTLA) and 48(CD196-CCR6) stained PC and MG/MT zone of the FOL; N° 12/37/66 (PD1) and CD152 intrafollicular activated cells (IAC), whereas N°50(CXCR5) stained IAC and MG and MT zone of the FOL; N° 14(GCET-1), 17(LMO2), 18 (KLHL-6), N°70 (B7H4) stained GC; N° 29 GC and DR; N° 20/108(FCRL1), 21/110(FCRL2) MG/MT/GC and PC; N° 94 (HVEM), 114 (BLK154), 235 (BAFF-R) MG/MT zone; N° 97 (TCL1) nucleus of the FOL/MT zone; N° 27 (weak), 128-CD38 PC. We hope that our efforts may be useful to better understanding the tissue distribution of the analyzed reagents
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