bluuebunny/crossref_metadata_2025_split huggingface dataset:
PUVA-induced lichen planus pemphigoides
Authors: Kuramoto N. , Kishimoto S. , Shibagaki R. , Yasuno H. 
Published: March 2003

Abstract
A 72-year-old woman had suffered from parapsoriasis en plaque (large plaque type) controlled by topically applied psoralen ultraviolet A (PUVA) therapy. The parapsoriasis lesions gradually disappeared, but numerous tiny red papules with pruritus appeared over the forearms and lower legs 120 days after starting PUVA therapy. These papules developed to form violaceous plaques. Histological findings demonstrated the characteristics of lichen planus. Two months later, tense bullae developed on the plaques and on uninvolved skin of the limbs. These were subepidermal, with linear deposits of IgG and C3 along the basement membrane zone (BMZ) in immunofluorescence of peribullous skin, and immunodeposits of type IV collagen along the floor of the bullae. We therefore, diagnosed lichen planus pemphigoides (LPP). Using systemic and topical steroid therapy, the lesions rapidly resolved and there has been no recurrence. This case suggests that the combination of basal cell injuries caused by chronic inflammation and PUVA therapy could expose BMZ components to autoreactive lymphocytes and induce LPP.
Coexistence of psoriasis and linear IgA bullous dermatosis
Authors: Takagi Y. , Sawada S. , Yamauchi M. , Amagai M. , Niimura M. 
Published: March 2003

Abstract
Linear IgA bullous dermatosis (LABD) is characterized by IgA autoantibodies against components of the basement membrane zone (BMZ). A 97-kDa protein is one of the major autoantigens associated with this disease. We report a 68-year-old man who developed LABD after a 3-year history of psoriasis and in the context of active hepatitis C virus infection. He had been treated with cyclosporin for psoriasis for about 9 months. Histologically, there was a subepidermal blister containing neutrophils and eosinophils with lymphocytes infiltrating predominantly in the dermis. Direct immunofluorescent staining showed linear IgA deposition at the BMZ. The patient’s IgA autoantibodies bound exclusively to the epidermal side of 1 mol/L salt-split normal human skin. Immunoblot analysis identified a 97-kDa autoantigen in epidermal extracts. This appears to be the first case of LABD with IgA autoantibodies against a 97-kDa autoantigen, associated with psoriasis and hepatitis C virus infection.
Squamous cell carcinoma arising in Hailey–Hailey disease of the vulva
Authors: Cockayne S.E. , Rassl D.M. , Thomas S.E. 
Published: March 2003

Abstract
A 61–year-old woman, who was known to have Hailey–Hailey disease, presented with increasing vulval soreness. Biopsy showed vulval intraepithelial neoplasia (VIN) 3 and subsequent histology from a vulvectomy specimen showed extensive VIN with early invasive squamous cell carcinoma. This may be another example of chronic inflammation of the vulval area leading to the development of squamous cell carcinoma. However, in this case, chronic human papillomavirus may also have played a part, leading to VIN and reactivation of the Hailey–Hailey disease. We can find no previous reports of squamous cell carcinoma developing in the setting of Hailey–Hailey disease.
A randomized trial of amorolfine 5% solution nail lacquer combined with oral terbinafine compared with terbinafine alone in the treatment of dermatophytic toenail onychomycoses affecting the matrix region
Authors: Baran R. , Feuilhade M. , Datry A. , Goettmann S. , Pietrini P. , Viguie C. , Badillet G. , Larnier C. , Czernielewski J. 
Published: March 2003

AbstractIn view of recent advances in the development of antifungal agents, this study examined the possible synergy of two new antifungal agents, terbinafine and amorolfine. The study compared two different courses of terbinafine treatment combined with amorolfine 5% solution nail lacquer. Terbinafine was given orally for 6 (AT6 group) or 12 weeks (AT12 group) and amorolfine nail lacquer applied weekly for 15 months. A control group received terbinafine alone for 12 weeks. This was a randomized, prospective, open study of severe dermatophyte toenail onychomycosis with matrix region involvement. Nail samples were taken before the start of the study, at inclusion and at the visits at 6 weeks, 3, 9, 15 and 18 months. To assess the value of such combined therapy we chose an early parameter as the principal outcome variable, which was the result of mycological examination, including direct microscopy and culture, at 3 months (allowing a margin of 15 days). The secondary parameters of success were the mycological results at the later visits, clinical evaluation and a combined mycological–clinical response. Safety and tolerance were also assessed. Adverse events were recorded and liver function tests were performed monthly during the terbinafine treatment. Of the 147 patients included in the trial, 121 attended the 3-month visit, within a time limit of 15 days of 3 months after the beginning of treatment: 40 in the AT6 group, 40 in the AT12 group and 41 in the control group. In all, 32 of 121 patients (26·4%) had negative mycological results on direct microscopy and culture: 14 of 40 (35·0%) in the AT6 group, 11 of 40 (27·5%) in the AT12 group and seven of 41 (17·1%) in the control group. The cure rate for the global (mycological and clinical cure) response measured at 18 months in 145 patients was 44·0% (22 patients) in the AT6 group, 72·3% (34 patients) in the AT12 group and 37·5% (18 patients) in the terbinafine group. These results suggest that the combination of amorolfine and terbinafine may be of value in the treatment of severe onychomycosis. At the same time a pilot pharmacoeconomic analysis was performed demonstrating a better cost per cure ratio for the patients receiving combination treatment.
Treatment of verrucous carcinoma of vulva with acitretin
Authors: Mehta R.K. , Rytina E. , Sterling J.C. 
Published: March 2003

Abstract
We describe a 60-year-old patient with verrucous carcinoma of the vulva, which recurred 6 years after simple vulvectomy and radiotherapy. Treatment with acitretin led to significant improvement and ongoing disease control has been achieved with low-dose maintenance therapy of 10 mg acitretin daily.
Cone and platelet analyser (CPA): a new test for the prediction of bleeding among thrombocytopenic patients
Authors: Kenet  , Lubetsky  , Shenkman  , Tamarin  , Dardik  , Rechavi  , Barzilai  , Martinowitz  , Savion  , Varon  
Published: March 2003

The risk of bleeding among thrombocytopenic patients was evaluated using our new cone and platelet analyser (CPA) test. Using this test, adherence of platelets was quantitated on extracellular matrix and expressed as percent of surface coverage (SC) and the average size (AS) of aggregates. 42 thrombocytopenic patients with ITP (n=23), post chemotherapy (n=12) and others (n=7) were tested over a total of 82 visits. On each visit, complete blood count and CPA tests were performed and patients were evaluated for evidence of bleeding (found in 40 visits).Bleeding patients had significantly lower platelet counts (27.4 ± 22.0 v 47.1 ± 21.0 × 109/l), lower haematocrit values (30.2 ± 8.1 v 35.2 ± 6.6%), lower MPV (6.83 ± 1.89 v 8.98 ± 1.13 fl), and lower SC (4.87 ± 3.95 v 10.33 ± 5.48%) and AS (33.99 ± 14.94 v 52.9 ± 24.34 μm2). Univariate analysis yielded platelet count 20.0 × 109/l, MPV  8fl, haematocrit <35%, SC < 5%, AS  40 μm2 as significantly associated with bleeding, whereas only MPV and SC were associated with bleeding (OR 6.95, CI 2.25–21.46 and OR 4.27, CI 1.29–14.16, respectively) by multivariate analysis. When taken together, 21/22 of patients (95%) with both low SC (<5%) and low MPV (<8.0 fl) had bleeding symptoms, whereas only 9/43 (21%) patients with both these parameters above these values experienced bleeding symptoms.We conclude that the CPA test and the parameter SC (<5%) together with MPV (8 fl) might be used as independent predictors of bleeding in the management of thrombocytopenic patients.
Liver iron and fibrosis during long‐term treatment with deferiprone in Swiss thalassaemic patients
Authors: TÖndury Petrign , Zimmermann Arthur , Nielsen Peter , Hirt Andreas 
Published: March 2003

Serum ferritin levels, hepatic histology and iron concentration were studied in a ‘veteran’ group of seven Swiss β‐thalassaemic patients after 93–99 months of treatment with the oral iron chelator deferiprone (L1), and another four patients who had received 54–82 months of L1 therapy. Despite continuous compliance, unexplained resurgence of serum ferritin levels occurred in 4/7 patients of the ‘veteran’ group after 4–5 years on L1. In three of these a concomitant increase of liver iron was also observed.Hepatic histology revealed significantly higher degrees of fibrosis in 6/11 hepatitis C (HC)‐positive patients (fibrosis scores 1–5, mean 3.0) than in the HC‐negative group (fibrosis score 0–2, mean 0.8). Two HC‐negative patients had no detectable fibrosis after 98 and 93 months on deferiprone. Therefore the hepatic pathology in these patients cannot definitely be attributed as a side‐effect of deferiprone. Chronic active hepatitis C and the accumulation of iron are the major causative factors to be considered.
Thioguanine versus mercaptopurine for therapy of childhood lymphoblastic leukaemia: a comparison of haematological toxicity and drug metabolite concentrations
Authors: Lancaster  , Lennard  , Rowland  , Vora  , Lilleyman  
Published: March 2003

As a prelude to a nationwide randomized trial of thioguanine (TG) versus mercaptopurine (MP) for childhood lymphoblastic leukaemia we compared a pilot group of 23 children taking TG with a matched group taking MP. We assessed drug tolerance based on haematological toxicity and measured erythrocyte (RBC) concentrations of thioguanine nucleotides (TGN).The median tolerated dose of TG was 30 mg/m2 compared to 55 mg/m2 for MP. There was no difference in the pattern of anaemia or neutropenia between the two groups, but dose‐limiting thrombocytopenia was more evident in the TG children (P < 0.001), four of whom had a decrease in platelet count to <20 × 109/l compared to only one on MP. The median RBC TGN concentration for those on 40 mg/m2 TG was 1726 pmol/8 × 108 RBCs compared with 308 pmol/8 × 108 RBCs for those on 75 mg/m2 MP (P < 0.0001). There was an inverse correlation between RBC TGNs and neutrophil count in the MP group but not in those on TG. No correlation between metabolite concentration and thrombocytopenia was found in either group.These results provide further evidence that TG has a selective effect on platelets. They also showed that RBC TGN were, on average, 5‐fold higher in those taking TG but did not obviously relate to myelotoxicity as found in children on MP. The higher concentrations seen may partly reflect the erythrocyte's ability to metabolize TG directly to TGN by pathways not open to MP.
Antibodies to prothrombin in antiphospholipid syndrome and inflammatory disorders
Authors: Guerin Jan , Smith Owen , White Barry , Sweetman Gertrude , Feighery Conleth , Jackson John 
Published: March 2003

Antiphospholipid antibodies associated with the antiphospholipid syndrome (APS) have been shown to bind plasma proteins, particularly beta 2‐glycoprotein I (β2‐GPI). In this study the incidence of antibodies to solid‐phase prothrombin was examined in patients with antiphospholipid syndrome and a variety of other inflammatory disorders.Significantly elevated levels of IgG anti‐prothrombin (anti‐PT) antibodies were detected in 63% of patients with APS (n = 27, median 22 arbitrary units: AU), 33% with SLE (n = 92, median 14 AU), 45% with rheumatoid factor (n = 22, median 16 AU), 21% with carotid artery stenosis (n = 21, median 15 AU), 32% with stroke (n = 38, median 13 AU), 67% of patients with a false positive serology for syphilis (n = 21, median 24 AU), 37% with HIV (n = 30, median 14 AU), 29% with syphilis (n = 14, median 19 AU) and 3% with infectious mononucleosis (n = 30, median 9 AU). In addition, a group of lupus anticoagulant (LA) positive patients (n = 48) was examined for antibodies to prothrombin, β2‐GPI and cardiolipin. 10 (21%) patients had raised levels of IgG anti‐PT antibodies, 30 (62%) had significantly elevated levels of anti‐β2‐GPI antibodies and 15 (31%) had elevated levels of anticardiolipin antibodies (ACA). Of the LA‐positive patients, 15 (43%) were identified with definite APS, eight (23%) with probable APS, two (6%) with possible APS and 10 (28%) patients had no clinical evidence of APS.In conclusion, antibodies to prothrombin were found in a variety of inflammatory disorders and were therefore not specific for the APS. However, identification of the plasma proteins recognized by antibodies from patients with APS may provide insight into the pathogenic mechanisms involved in the heterogenous clinical manifestations of the APS.
Multiple myeloma related cells in patients undergoing autologous peripheral blood stem cell transplantation
Authors: Guikema Jeroen E. J. , Vellenga Edo , Veeneman Jorden M. , Hovenga Sjoerd , Bakkus Marleen H. C. , Klip Harry , Bos Nicolaas A. 
Published: March 2003

A high incidence of oligoclonal serum M‐components is observed in multiple myeloma (MM) patients treated with autologous stem cell transplantation (ASCT). To determine whether these M‐components are produced by myeloma clonally related cells or caused by an aberrant B‐cell regeneration we analysed by semi‐nested ASO‐RT‐PCR and DNA sequencing the immunoglobulin (Ig) variable genes (VH) obtained from bone marrow samples obtained before and after transplantation and peripheral blood stem cell (PBSC) samples from seven patients.Myeloma clonally related cells are identifiable by the expression of variant Ig heavy chain isotypes and were detected in two patients at presentation. No myeloma clonally related cells were found in post‐transplantation samples (n = 7) in spite of the appearance of new serum M‐components. However, in two cases we amplified sequences from post‐transplantation bone marrow cells that were able to bind to the B‐cell clone‐specific CDR3 oligonucleotides but showed no further similarity regarding the VDJ rearrangement.These data indicate that serum oligoclonality post‐transplantation is not caused by myeloma clonally related B cells but rather by the regenerating B‐cell compartment.
Thrombomodulin with the Asp468Tyr mutation is expressed on the cell surface with normal cofactor activity for protein C activation
Authors: Nakazawa Fumie , Koyama Takatoshi , Saito Takako , Shibakura Misako , Yoshinaga Haruhiko , Chung Dong Hui , Kamiyama Ryuichi , Hirosawa Shinsaku 
Published: March 2003

Thrombomodulin (TM) is an endothelial cell glycoprotein that acts as an anticoagulant. Mutation in the TM gene is a potential risk factor for thrombosis. The first TM mutation identified was a heterozygous substitution of T for G at nucleotide position 1456, which predicted Asp468 with Tyr in a Ser/Thr‐rich domain. To evaluate the reported TM gene mutation as a possible cause of thrombosis, we transiently tranfected a vector for TM gene carrying the mutation to mammalian COS7 cells.TM antigen levels in lysates of cells transfected with variant TM were comparable to those in preparations of normal TM. The TM cofactor activity for protein C (PC) activation on the variant TM‐expressing cells was similar to that of the control. The Michaelis constant Km and Vmax. of variant TM for PC activation were shown to be similar compared to those of normal TM. The affinity of each TM for thrombin in PC activation was also similar. We obtained several stable cell lines expressing normal and variant TM. Lysate of the cell lines with normal and variant TM genes had a similar expression level of TM antigen. Pulse‐chase analysis showed that normal and variant TM were glycosylated and resistant to endoglycosidase H, indicating that the variant TM was expressed on the cell surface in a mature form.Variant TM protein is apparently expressed on the cell surface with normal cofactor activity for PC activation. It is unlikely that the TM variant directly causes thrombosis by mechanism of reduced expression or impaired cofactor activity for PC activation, which comprises a major anticoagulant activity of TM.
Complete remission rate and outcome after intensive treatment of 177 patients under 75 years of age with IgG myeloma defining a circumscribed disease entity with a new staging system
Authors: Sirohi Bhawna , Powles Ray , Mehta Jayesh , Raje Noopur , Kulkarni Samar , Ramiah Veshana , Saso Radovan , Horton Clive , Bhagwati Niyati , Singhal Seema , Treleaven Jennifer 
Published: March 2003

Because the presence of IgG paraprotein in the blood is clear cut, it makes IgG myeloma a more circumscribed disease than myeloma as a whole in which to study treatment efficacy, particularly relating to complete remission (CR).Between May 1989 and December 1997, 177 consecutive patients with IgG myeloma who were <75 years old were seen, of whom 153 entered a sequential therapy (ST) programme of initial courses of C‐VAMP infusional chemotherapy (IC), high‐dose treatment (with or without stem cell rescue) (119 patients) and maintenance interferon (87 patients).74/153 (48.4%) patients entered CR. Median overall survival (OS) and event‐free survival (EFS) were 4.9 and 2.1 years, respectively. Multivariate analysis at presentation showed OS was significantly prolonged for β2M <2.7 mg/l and age <median 52, whilst β2M <2.7 mg/l and Hb >8.5 g/dl predicted for longer EFS. For CR patients, age <median 51 years, absence of Bence‐Jones proteinuria (BJP), male sex and white blood cells (WBC) <7 × 109/l predicted for a longer OS. Longer length of first CR was predicted by absence of BJP at presentation (P = 0.03) and fewer than five courses of IC (P = 0.02) to attain CR.We have therefore been able to refine the use of ST in IgG myeloma, redefine CR as a ‘macro’ endpoint, and propose a new staging system for IgG myelomas. Analysis of 41 comparable IgA patients showed IgG to be a distinct entity.
Hepatocyte growth factor is secreted by osteoblasts and cooperatively permits the survival of haematopoietic progenitors
Authors: Taichman Russell S. , Reilly Marcelle J. , Verma Rama S. , Ehrenman Karen , Emerson Stephen G. 
Published: March 2003

Human osteoblasts (HOBs) support the growth of human haematopoietic progenitor cells, and support the survival and limited expansion of long‐term culture‐initiating cells. Using human CD34+ cells and the murine myelomonocytic cell line NFS‐60 as targets, we previously found that one component of HOB‐derived haematopoietic activity is cell‐associated granulocyte colony‐stimulating factor (G‐CSF). However, antibody failed to neutralize all the activity, suggesting that more than one factor supports haematopoietic cells. In the present investigations, we asked whether the HOB‐derived, non‐G‐CSF secreted activity was as a result of other known growth factors. We found that, among the cytokines expressed by HOBs, only hepatocyte growth factor (HGF) and G‐CSF stimulated NFS‐60 cell proliferation. HOB cells and osteosarcoma cells secreted biologically active HGF, although the levels varied considerably. Moreover, addition of neutralizing HGF antibody to CD34+ cell/HOB co‐cultures resulted in a significant reduction (≈50%) in the ability of the HOBs to support haematopoietic progenitor cells. These results suggest that a major component of osteoblast‐derived haematopoietic activity is HGF. Secretion of HGF, in concert with cell‐associated cytokines such as G‐CSF, may account for the stem cell‐stimulating activities of osteogenic cells and, thereby, the unique stem cell‐supporting role of the osteoblasts within the bone marrow microenvironment.
The granulocyte colony‐stimulating factor receptor supports erythroid differentiation in the absence of the erythropoietin receptor or Stat5
Authors: Millot Gaël A. , Svinarchuk Fédor , Lacout Catherine , Vainchenker William , Dumenil Dominique 
Published: March 2003

To evaluate the functional conservation of signal transduction mechanisms between haematopoietic receptors and to characterize the molecules activated in this phenomenon, we introduced granulocyte colony‐stimulating factor receptor (G‐CSFR) cDNA into mouse fetal liver cells using a retroviral vector. In semi‐solid medium assays, G‐CSFR‐infected cells gave rise to all types of colonies [granulocyte‐macrophage (GM), megakaryocyte (MK) and mixed lineage (GEMM) colony‐forming units (CFU) and erythroid burst‐forming units (BFU‐E)] in the presence of G‐CSF alone. The direct effect of G‐CSF on erythroid differentiation of G‐CSFR‐transduced erythroid progenitors was demonstrated by the development of erythroid colonies using G‐CSFR‐expressing Lin− cells cloned at one cell per well in liquid culture in the presence of G‐CSF. Interestingly, while Stat5, but not Stat3, was activated in erythroid cells in response to erythropoietin (EPO), both were activated in erythroid and granulocytic cells stimulated by G‐CSF. Furthermore, G‐CSF induced the growth of erythroid colonies from G‐CSFR‐expressing fetal liver cells from EPO receptor−/− (EPO‐R−/−) or Stat5a−/− Stat5b−/− mice, demonstrating that erythroid differentiation can occur in the absence of EPO‐R or Stat5. These data show that forced expression of G‐CSFR allows G‐CSF‐dependent multilineage proliferation and differentiation of haematopoietic progenitors and rescues EPO‐R−/− erythroid cells. While G‐CSF induces Stat5 activation in G‐CSFR‐expressing erythroid cells, this activation is not necessary for the terminal erythroid differentiation induced by G‐CSF.
Killer T‐cell induction in patients with blastic natural killer cell lymphoma/leukaemia: implications for successful treatment and possible therapeutic strategies
Authors: Yamada Osamu , Ichikawa Masako , Okamoto Takamitsu , Park Chisen , Motoji Toshiko , Mizoguchi Hideaki , Shibuya Akira 
Published: March 2003

A rare form of putative natural killer (NK) cell lymphoma called blastic NK cell lymphoma appears to be clinicopathologically distinctive in showing a homogenous lymphoblast, variable expression of CD2, CD4, CD56 and TdT, negative for surface CD3, T‐cell receptor antigen, CD16, CD34 and lack of association with Epstein–Barr virus (EBV). We report two patients with blastic NK cell lymphoma and describe the interesting clinical studies. The patients presented with cutaneous plaques. Both patients had adenopathy, and one had marrow involvement at presentation. Unlike in many NK and NK‐like T‐cell disorders, azurophilic cytoplasmic granules were absent. They expressed intermediate density CD45. In addition, the cells were positive for HLA‐DR, CD2, CD4, CD56 and TdT, and negative for EBV transcripts. In spite of the advanced clinical stage, complete remission was achieved by conventional chemotherapy. After interleukin 2 expansion of tumour‐infiltrating bone marrow and lymph node cells from the patients, cytotoxic T‐cell lines with rearranged T‐cell receptor genes were established. They showed specific killing activity against autologous tumour cells in an MHC‐restricted fashion, with possible implications for treatment. In addition, upon cessation of maintenance chemotherapy, one patient developed overt leukaemia with blasts expressing CD33 antigens, suggesting a continuous spectrum of blastic NK cell lymphoma to myeloid/NK cell precursor acute leukaemia.