Biomedical subjects

K Schäkel

Publications and source records attributed to K Schäkel.

7 recordsLinked to original sources

PubMed2003

Severe epidermal necrolysis after treatment with imatinib and consecutive allogeneic hematopoietic stem cell transplantation.

Imatinib is a new promising therapeutic option for chronic myeloid leukemia (CML) with efficacy even in the blast phase of the disease. However, most patients treated with imatinib in the blast phase develop progressive disease rapidly. Thus, treatment with imatinib has to be followed by other treatment strategies. The normally mild to moderate side effects of imatinib including skin rashes might therefore be aggravated. Here, we describe a patient with severe epidermal necrolysis after treatment with imatinib and consecutive allogeneic hematopoietic stem cell transplantation. Prolonged inhibition of platelet-derived growth factor by imatinib may be an explanation for this observed skin toxicity.

Benzamides↗

PubMed1999

Differential expression of alpha2-6 sialylated polylactosamine structures by human B and T cells.

We found that human peripheral B and T cells differed in the surface expression of alpha2-6 sialylated type 2 chain glycans. In contrast to B cells, T cells expressed only sialoglycans with repeated N-acetyllactosamine (Galss1-4GlcNAc) disaccharides. This finding was based on the specificity of the monoclonal antibodies HB6, HB9 (CD24), HD66 (CDw76), FB21, and CRIS4 (CDw76) with the alpha2-6 sialylated model gangliosides IV6NeuAcnLc4Cer (2-6 SPG), VI6NeuAcnLc6Cer (2-6 SnHC), VIII6NeuAcnLc8Cer (2-6 SnOC), and X6NeuAcnLc10Cer (2-6 SnDC). We found that, in addition to their common requirement of an alpha2-6 bound terminal sialic acid for binding, the antibodies displayed preferences for the length of the carbohydrate backbones. Some of them bound mainly to 2-6 SPG with one N-acetyllactosamine (LacNAc) unit (HB9, HD66); others preferentially to 2-6 SnHC and 2-6 SnOC, with two and three LacNAc units, respectively (HB6 and FB21); and one of them exclusively to very polar alpha2-6 sialylated type 2 chain antigens (CRIS4) such as to 2-6 SnOC and even more polar gangliosides with three and more LacNAc units. These specificities could be correlated with the cellular binding of the antibodies as follows: whereas all antibodies bound to human CD 19 positive peripheral B cells, their reactivity with CD3 positive T cells was either nearly lacking (HD66, HB9), intermediate (about 65%: HB6, FB21) or strongly positive (CRIS4, 95%). Thus, the binding of the antibodies to 2-6 sialylated glycans with multiple lactosamine units appeared to determine their binding to T-cells.

Amino Sugars↗

PubMed1999

M-DC8+ leukocytes--a novel human dendritic cell population.

Dendritic cells (DC) constitute a heterogeneous leukocyte population having in common a unique capacity to induce primary T cell responses and are therefore most attractive candidates for immunomodulatory strategies. Two populations of blood DC (CD11c+ CD123(dim) and CD11c- CD123(high)) have been defined so far. However, their direct isolation for experimental purposes is hampered by their low frequency and by the lack of selective markers allowing large scale purification from blood. Here we describe the monoclonal antibody (mAb) M-DC8, which was generated by immunizing mice with highly enriched blood DC. This mAb specifically reacts with 0.2-1% of blood leukocytes and enables their direct isolation by a one-step immunomagnetic procedure from fresh mononuclear cells. These cells can be differentiated from T cells, B cells, NK cells and monocytes using lineage-specific antibodies. M-DC8+ cells express HLA class II molecules, CD33 and low levels of the costimulatory molecules CD86 and CD40. Upon in vitro culture M-DC8+ cells spontaneously mature into cells with the phenotype of highly stimulatory cells as documented by the upregulation of HLA-DR, CD86 and CD40; in parallel CD80 expression is induced. M-DC8+ cells display an outstanding capacity to present antigen. In particular, they proved to be excellent stimulators of autologous mixed leukocyte reaction and to activate T cells against primary antigens such as keyhole limpet hemocyanin. Furthermore, they induce differentiation of purified allogeneic cytotoxic T cells into alloantigen-specific cytotoxic effector cells. While the phenotypical analysis reveals similarities with the two known blood DC populations, the characteristic expression of FcgammaRIII (CD16) and the M-DC8 antigen clearly defines them as a novel population of blood DC. The mAb M-DC8 might thus be a valuable tool to determine circulating DC for diagnostic purposes and to isolate these cells for studies of antigen-specific T cell priming.

Animals↗

PubMed1998

A novel dendritic cell population in human blood: one-step immunomagnetic isolation by a specific mAb (M-DC8) and in vitro priming of cytotoxic T lymphocytes.

Originating from a common progenitor cell, dendritic cells (DC) appear to develop along early branched pathways into various yet ill-defined subpopulations residing at various sites throughout the body where they capture and present antigen in the most professional fashion. Here we give evidence for a unique subpopulation of human DC circulating in blood that account for 0.5-1% of blood leukocytes only, their most specific characteristic being the expression of a cell surface protein recognized by a novel monoclonal antibody (M-DC8) which enables their isolation by a one-step immunomagnetic procedure. The isolated cells (> 97% pure) present morphologically as typical dendritic cells. They express the Fc(gamma)RIII (CD16), so far not found on DC, and avidly phagocytose latex beads as well as opsonized erythrocytes. These cells not only present antigens efficiently to naive T cells but also induce purified CD8+ T cells to become alloantigen-specific cytotoxic cells. Furthermore, when loaded with a tyrosinase-derived peptide they stimulate T cells from normal donors and melanoma patients to exhibit MHC-restricted specific cytotoxicity against melanoma cells.

Antibodies, Monoclonal↗

PubMed1997

New aspects in a murine model for extrahepatic biliary atresia.

The cause of extrahepatic biliary atresia (EHBA) remains unknown, and even an animal model is still lacking. Observations in a murine infectious model (newborn Balb/c mice infected with rhesus rotavirus group A [RRV]) reported extrahepatic biliary obstruction similar to findings in children who have EHBA. In the present study, this animal experiment was repeated, and the clinical and histomorphologic changes were observed over 3 weeks. Eighty-nine newborn mice were infected with RRV, and 67% showed signs of cholestasis and delayed growth. Eight of these animals recovered spontaneously whereas the others remained icteric. Fourty-six pups were prepared for microscopic examination following a 2-day interval. From the fifth day, the whole biliary tract showed edematous swelling with cellular infiltration. Ten days later, in the extrahepatic bile duct, a transformation took place in which concentric infiltration led to complete obstruction, sometimes with prestenotic dilatation. The intrahepatic changes showed reactive necrosis and proliferation of the small bile ducts. In one 19-day-old mouse, a ballooning dilatation was observed, similar to a developing choledochal cyst. Infection with RRV induces in newborn Balb/c mice a cholestatic clinical picture with different courses of the disease leading mostly to complete biliary obstruction and secondary hepatic changes similar to EHBA in children. This is the first animal model for EHBA with complete obstruction of the extrahepatic bile duct induced by infection. These findings present a new basis for further studies.

Animals↗

PubMed1996

Detection of group C rotavirus in infants with extrahepatic biliary atresia.

The purpose of this retrospective study was to examine liver tissue from patients with cholestatic disease for the presence of group C rotavirus RNA. The reverse transcriptase-polymerase chain reaction (PCR) for genes 5 and 6 was used, and the PCR products were subjected to liquid hybridization with a 32P-labeled probe. A second amplification with nested primers was also used. Samples from 32 subjects (20 with biliary atresia or choledochal cyst and 12 controls) were tested. Ten of 20 biliary atresia patients were positive for group C rotavirus RNA; no controls were positive (P < .003). Three of the positive patients were positive for both genes 5 and 6. Six of the 10 had > 1 sample that was positive. These data suggest a possible relationship between group C rotavirus and extrahepatic biliary atresia in the 10 patients in whom virus RNA was detected.

Autoradiography↗

PubMed1995

[Budesonide].

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Adult↗