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During the past two decades a few clinical reports have suggested that the therapeutic efficacy of cyclophosphamide against malignant tumors was partly mediated by drug effects on host immune mechanisms. This action was strictly dose-dependent: immunostimulation was only evident in the low dose range, whereas immunosuppression became significant at(More)
Signaling output of bone morphogenetic proteins (BMPs) is determined by two sets of opposing interactions, one with heterotetrameric complexes of cell surface receptors, the other with secreted antagonists that act as ligand traps. We identified two mutations (N445K,T) in patients with multiple synostosis syndrome (SYM1) in the BMP-related ligand GDF5.(More)
Beta-D-glucosyl-ifosfamide mustard (D 19575, glc-IPM, INN = glufosfamide) is a new agent for cancer chemotherapy. Its mode of action, which is only partly understood, was investigated at the DNA level. In the breast carcinoma cell line MCF7 glufosfamide inhibited both the synthesis of DNA and protein in a dose-dependent manner, as shown by the decreased(More)
Here we describe 2 mutations in growth and differentiation factor 5 (GDF5) that alter receptor-binding affinities. They cause brachydactyly type A2 (L441P) and symphalangism (R438L), conditions previously associated with mutations in the GDF5 receptor bone morphogenetic protein receptor type 1b (BMPR1B) and the BMP antagonist NOGGIN, respectively. We(More)
This report describes work performed by the Collaborative Agent Design Research Center (CADRC) over the past several years in the design and implementation of collaborative, computer-based, decision-support systems, mostly for military applications. In these systems multiple components, either program modules or separate processes (i.e., software agents),(More)
The chemotherapy of malignant tumors with oxazaphosphorine cytostatics, e.g., cyclophosphamide (CP) and ifosfamide, is limited by their severe urotoxic side effects. As a result of cytotoxic damage, the proliferation of the urinary bladder urothelium is considerably stimulated during an intensive reparative regeneration. The recently developed uroprotector(More)
For the past 20 years the US military services have suffered under the limitations of stove-piped computer software applications that function as discrete entities within a fragmented data-processing environment. Lack of interoperability has been identified by numerous think tanks, advisory boards, and studies, as the primary information systems problem (e.(More)