Langerhans cell histiocytosis (LCH) is a proliferative histiocytic disorder of unknown cause originating from dendritic cells. The clinical presentation of LCH is highly variable. Although the features of this disease have been well described in children, they remain poorly defined in adults. Here, we review the current knowledge about adult LCH, focussing on clinical presentation, diagnosis, treatment, and prognosis.

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Normal hemostasis requires von Willebrand factor (VWF) to support platelet adhesion and aggregation at sites of vascular injury. VWF is a multimeric glycoprotein built from identical subunits that contain binding sites for both platelet glycoprotein receptors and collagen. The adhesive activity of VWF depends on the size of its multimers, which range from 500 to over 10 000 kDa. There is good evidence that the high-molecular-weight multimers (HMWM), which are 5000–10 000 kDa, are the most effective in supporting interaction with collagen and platelet receptors and in facilitating wound healing under conditions of shear stress. Thus, these HMWM of VWF are of particular clinical interest. The unusually large multimers of VWF are, under normal conditions, cleaved by the plasma metalloproteinase ADAMTS13 to smaller, less adhesive multimers. A reduction or lack of HMWM, owing to a multimerization defect of VWF or to an increased susceptibility of VWF for ADAMTS13, leads to a functionally impaired VWF and the particular type 2A of von Willebrand disease. This review considers the biology and function of VWF multimers with a particular focus on the characterization of HMWM – their production, storage, release, degradation, and role in normal physiology. Evidence from basic research and the study of clinical diseases and their management highlight a pivotal role for the HMWM of VWF in hemostasis.

Summary:blood stem cell transplantation than after allo-BMT, resulting in less morbidity and mortality. 3,4 There are relatively little data about the reconstitution of lymphocyte subThe expression of CD45RA + and CD45RO + isoforms on T cells and the recovery of B lymphocytes and NK cells sets after PBSCT. 5 B cell reconstitution is severely compromised for months to years after allo-BMT, 6 especially in after autologous peripheral blood stem cell transplantation (PBSCT) were studied during the early period patients with chronic graft-versus-host disease (GVHD). CD45RA+ subset. The regeneration in the second post-transplant year. Storek et al 12 showed that a second round of B cell ontogeny occurred in transof the CD4 + cells was markedly delayed, but was faster in the PBSCT recipients, mainly because of the faster plant recipients without chronic GVHD. Does a faster recovery of B lymphocytes after PBSCT imply a faster recovery of the mature CD4 + CD45RO + subset. The pattern of surface antigens on T lymphocytes after transrecapitulation of ontogeny following PBSCT than after allo-BMT without cGVHD? Or, does a different T lymphoplantation did not resemble the antigen pattern on cord blood cells. The CD19 + CD20 + cells recovered earlier in cyte regeneration after PBSCT influence the faster B cell recovery, since a lack of appropiate T cell support is proven the PBSCT group and remained compromised after allo-BMT during the time studied. The faster B lymphoto contribute to deficiencies of B cell function. 13-17To date, the mechanisms of T cell regeneration are not cyte regeneration correlates with the faster reconstitution of the mature CD4 with CD45RA monoclonal antibodies. The CD45RO + isoforms increase thereafter to reach about 50% in adult life. 18Keywords: lymphocyte reconstitution; PBSCT; T cell isoforms; CD4 + CD45RO +The expression of CD45RO receptors characterizes a T cell as a mature cell of the memory type, responding to antigen stimulation, 19 whereas the CD45RA receptor-positive cells are considered to be immature and naive. They may convert Allogeneic bone marrow transplantation and peripheral to mature CD45RO + cells after stimulation. The expression blood stem cell transplantation have been proved to be of the CD45RO antigen, however, seems to be bidirectional effective therapies for patients with hematopoietic maligand may revert to the CD45RA + isoform. 18nancies and a variety of solid tumors. 1 Intensive chemoThere is no evidence of recapitulation of ontogeny of T therapy with and without total body irradiation severely and cells post-transplant, but it appears that the thymus plays an irreversibly damages the bone marrow, which can be reconimportant role in T cell ontogeny.

CD133+ injection into ischemic myocardium was feasible and safe. Stem cell transplantation alone improved cardiac function in all patients. This technique might hold promise as an alternative to medical management in patients with severe ischemic heart failure who are ineligible for conventional revascularization.

We studied cultured canine keratinocytes to determine whether they could serve as targets for retrovirusmediated gene transfer and whether infected cells could persist after transplantation into dogs, a large random-bred model for gene transfer studies. Canine keratinocytes obtained from skin biopsy samples were cultured in vitro with lethally irradiated NIH 3T3 cells used as a feeder layer. The keratinocyte colonies consisted of squamous epithelium with numerous desmosomes, tonofilaments, and keratohyalin granules. In addition, the cells were strongly reactive with monoclonal antibodies to cytokeratin intermediate filament proteins. For the infection studies, we grew the keratinocytes on a feeder layer of lethally irradiated PA317 retrovirus packaging cells, which produced a helper-free amphotropic retroviral vector containing the neomycin phosphotransferase (neo) gene. After cocultivation, 34% (range, 10-76%) of the keratinocytes were found to be resistant to the neomycin analogue G418. Infected keratinocytes were then transplanted into the dog oforigin; 1% (range, <0.1-3%) of the keratinocytes obtained 27-130 days after transplantation from skin biopsy samples gave rise to G418-resistant colonies.We conclude that canine keratinocytes cultured in vitro can be infected efficiently with a neo gene-containing retroviral vector, and they show persistent G418 resistance for at least 130 days after transplantation into the skin donor.

Retroviral vectors carrying the neomycin phosphotransferase (neo) gene have been shown to confer G418 resistance to canine keratinocytes at relatively high frequency. To investigate the usefulness of keratinocytes as potential target cells for gene therapy, we used a retroviral vector (LASN) that contains both human adenosine deaminase (hADA) and neo genes. We show here that LASN-transduced canine keratinocytes expressed high levels of hADA, a human protein of therapeutic relevance. Selection of LASN-transduced keratinocytes in medium containing G418 resulted in a population of cells that expressed even higher levels of hADA, about 80-fold higher than the endogenous canine ADA level. However, the G418-selected cells had a reduced proliferative potential and altered morphology indicative of terminal differentiation. To test whether L-histidinol is more beneficial for selection of keratinocytes than G418, we constructed two retroviral vectors that contain both the neo and the histidinol dehydrogenase (hisD) genes. Cocultivation of primary keratinocytes with lethally irradiated PA317 retrovirus packaging cells that produce these vectors gave rise to 12-53% drug-resistant colonies in either G418 or L-histidinol. In contrast to G418, selection of transduced keratinocytes in L-histidinol had no apparent effect on the proliferative potential or morphology of drug-resistant cells containing the vectors. Given the utility of this selection system, two hisD-based generic constructs containing cloning sites for cDNA expression from either the retroviral promoter or from an internal human cytomegalovirus immediate early promoter were constructed. Our results suggest that hisD will be a useful selectable marker for use in studies of keratinocyte differentiation and for transfer of genes into keratinocytes for the purposes of gene therapy.

Nineteen patients with leukaemia, preleukaemia, and aplastic anaemia were treated by marrow transplantation from HLA-identical siblings. All were given postgrafting immunosuppression with a combination of methotrexate (days 1, 3, 6 and 11) and cyclosporin (days--1 to 180). In an attempt at reducing cyclosporin-associated toxicity, we explored whether the cyclosporin dose during the first 2 weeks could be decreased by 50% (from 3.0 to 1.5 mg/kg/d intravenously) without adversely affecting the incidence, onset, and severity of acute graft-versus-host disease (GVHD) and overall survival. Results from this pilot study were compared to those of a matched cohort of 38 patients given a standard dose of 3.0 mg cyclosporin/kg/d starting on day--1. The cumulative incidence of grade II and III acute GVHD in the 'low dose' cyclosporin group was 42% compared to 51% in the 'standard dose' group (P = 0.60). Three-year survival was 63% and 54% respectively (P = 0.59). Patients receiving the reduced cyclosporin dose during the first 14 d appeared to have less hepatotoxicity, and the methotrexate and cyclosporin doses administered were closer to the doses intended per protocol. We suggest that 'low dose' cyclosporin from day--1 to day 15 postgrafting might be as effective as 'standard dose' cyclosporin during that time period for the prevention of acute GVHD.