Pitfalls in diagnosing human poxvirus infections.
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Biomedical subjects
Publications and source records attributed to Klaus Eisendle.
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Borrelia burgdorferi is difficult to detect in routine biopsy material from patients with skin lesions of borreliosis. In this study, a new immunohistochemical method, focus floating microscopy (FFM), was developed to detect B burgdorferi in tissue sections and was compared with polymerase chain reaction (PCR). By using standard histologic equipment, tissue sections stained with a polyclonal B burgdorferi antibody were simultaneously scanned through 2 planes: horizontally in serpentines and vertically by focusing through the thickness of the section. Borrelia were detected in 47 of 71 ticks, 34 of 66 tick bites, 30 of 32 erythema chronicum migrans cases, 41 of 43 borrelial lymphocytomas, and 50 of 51 acrodermatitis chronica atrophicans cases. FFM proved to be more sensitive than PCR (96.0% vs 45.2%) and nearly equally specific (99.4% vs 100%). All 169 control cases, except 1 false-positive case of secondary syphilis, were negative with FFM. FFM is an easy, quick, and inexpensive method to reliably detect Borrelia in cutaneous tissue sections.
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Dendritic cells (DCs) are professional antigen-presenting cells playing a pivotal role in the induction of humoral and cellular immune responses, and chronic myeloid leukemia-derived DCs (CML-DCs) are possible candidates for inducing anti-leukemic immunity. This review describes phenotypic and functional features of DCs derived from CML patients as compared with DCs from healthy volunteers. In short, distinct deficiencies have been reported for CML-DCs, such as reduced migration, endocytosis, phagocytosis, antigen processing, DC maturation and cytokine production. DC abnormalities of CML patients can be abrogated by proper in vitro stimulation of leukemic DCs. This underscores the importance of proper generation and maturation of CML-DCs when considering clinical vaccination protocols.
Chronic myeloid leukaemia (CML) dendritic cells (DC) are possible candidates for inducing antileukaemic immunity. This study aimed to investigate the frequency, phenotype and function of blood-derived leukaemic DC in comparison with DC from healthy donors using flow cytometric assays and mixed leucocyte reaction (MLR). Immature leukaemic DC displayed a reduced endocytotic capacity as compared with healthy controls. Moreover, in vitro maturation of leukaemic DC was found to be deficient. Expression of CD80, CD83, CD86, and major histocompatibility complex class I and class II antigens were reduced on lipopolysaccharide (LPS)-matured leukaemic DC but were enhanced by a mixture of interleukin 1beta (IL-1beta), IL-6, tumour necrosis factor-alpha (TNF-alpha) and prostaglandin E2 (PGE2). Upon stimulation with bacterial LPS, intracellular TNF-alpha and IL-8 production was diminished in maturing DC from CML patients. This distinct cytokine deficiency was overcome when leukaemic DC were stimulated with cytokines/PGE2. MLR showed fully functional leukaemic DC after TNF-alpha-induced maturation, but a reduced proliferative alloresponse of leukaemic peripheral blood mononuclear cells. Further, intracellular production of cytokines in CML-derived T cells was markedly reduced. These data indicated that, in CML, the maturation response of leukaemic monocyte-derived DC to a natural stimulus like LPS is abnormal and may be caused by an aberrant TNF-alpha response in these cells. Thus, TNF-alpha alone or in combination with pro-inflammatory and T-cell stimulatory cytokines should be considered as an adjuvant for DC-based immunotherapy in CML.
Dendritic cells (DCs) are essential for initiating T-cell responses against either host- or leukaemia-specific antigens. We analysed phenotype, allostimulatory capacity and chimaerism of monocyte-derived DCs (moDCs) serially in 28 patients receiving allogeneic stem cell grafts after conventional myeloablative (n = 14) or reduced-intensity conditioning (RIC, n = 14). Although the recovery of phenotype and function of moDCs after myeloablative stem cell transplantation (SCT) was prompt, there was a trend to a lower expression of co-stimulatory molecules and major histocompatibility antigen class II antigens on mature moDCs in patients who had received RIC transplants. Similarly, the allostimulatory capacity of mature moDCs after RIC transplants was reduced for up to 6 months. Six out of 14 (43%) RIC transplant patients showed a pattern of mixed chimaerism within the first 3 months after transplant. RIC transplant patients with a mixed donor DC chimaerism had a significantly higher risk of relapse (75% versus 35% for patients with full donor DC chimaerism, P = 0.03) but a lower incidence of acute graft-versus-host disease (25% versus 56% for patients with full donor DC chimaerism, P = 0.157). These data, although preliminary, provide evidence that DC function is impaired after RIC transplants and that DC chimaerism may have an impact on graft-versus-host and graft-versus-leukaemia reactions.
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