The number of CD34+ cells harvested in a single leukapheresis can be predicted by measurement of the preceding day peripheral-blood circulating CD34+ concentration, and on the basis of these data a table of probable CD34+ cell yield has been constructed. This correlation may facilitate the efficient organization of leukapheresis procedures.

Summary:blood, but their numbers can be dramatically, albeit transiently, increased following treatment with conventional chemotherapy and administration of haemopoietic growth An essential prerequisite for successful procurement of sufficient autologous peripheral blood progenitor cells factors such as granulocyte colony-stimulating factor (G-CSF). 4,5 After mobilisation the PBPC are removed from the (PBPC) for engraftment is the optimal timing of collection. A number of surrogate markers of peripheral patient's circulation by apheresis and the adequacy of the collection is assessed by the product's content of nucleated blood progenitor cells were analysed to identify a single test which could predict the optimum time to harvest, cells, mononuclear cells, granulocyte-macrophage colonyforming units (CFU-GM) or CD34 + cells. providing at least 2 × 10 6 CD34 + cells/kg patient body weight. The study comprised 95 patients undergoingThere is a tremendous variation in the yield of haemopoietic progenitor cells obtained from patients following varied mobilisation regimens with chemotherapy and G-CSF for both solid tumours and haematological mobilisation which results in some patients requiring only one leucapheresis whereas others require two, three or even malignancies. One hundred and fifty-seven PBPC harvests were collected. Full blood counts (FBC) and four procedures. A number of different protocols are used to mobilise PBPC and the decision as to when to commence CD34 ؉ cell enumeration was performed on blood samples taken during the mobilisation period and the apheresis procedure is generally based on the patient's white cell count (WCC). Obviously the successful procureimmediately prior to leucapheresis (pre-harvest). All PBPC collections were assayed for colony-forming cells ment of sufficient PBPC to ensure haemopoietic engraftment is essential. To ensure that this goal is achiand CD34 ؉ cells in addition to a FBC. The white cell count on the day of harvest showed only weak correeved, with the least number of leucapheresis procedures, the optimal time for collection must be predicted as acculation with the total number of CD34 ؉ cells in the collection (r = 0.30). In contrast, the absolute number of circurately as possible. This is not only advantageous for the patient but also for both operational and financial lating CD34 + cells strongly correlated with the CD34 ؉ cell and CFU-GM yield of the corresponding apheresis efficiency. This study involved the analysis of the WCC, monoproduct. Provided the mobilisation sample contained у20 × 10 6 CD34 ؉ cells/ml, 94% of single collections, nuclear cell count (MNC), CD34 + cells and colony-forming units (CFU) on samples obtained from 95 patients with both performed the following day, contained у2 × 10 6

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The human protein tyrosine phosphatase non-receptor type 3 (PTPN3) is a PDZ (PSD-95/Dlg/ZO-1) domain-containing phosphatase with a tumor-suppressive or a tumor-promoting role in many cancers. Interestingly, the high-risk genital human papillomavirus (HPV) types 16 and 18 target the PDZ domain of PTPN3. The presence of a PDZ binding motif (PBM) on E6 confers interaction with a number of different cellular PDZ domain-containing proteins and is a marker of high oncogenic potential. Here, we report the molecular basis of interaction between the PDZ domain of PTPN3 and the PBM of the HPV E6 protein. We combined biophysical, NMR and X-ray experiments to investigate the structural and functional properties of the PDZ domain of PTPN3. We showed that the C-terminal sequences from viral proteins encompassing a PBM interact with PTPN3-PDZ with similar affinities to the endogenous PTPN3 ligand MAP kinase p38γ. PBM binding stabilizes the PDZ domain of PTPN3. We solved the X-ray structure of the PDZ domain of PTPN3 in complex with the PBM of the HPV E6 protein. The crystal structure and the NMR chemical shift mapping of the PTPN3-PDZ/peptide complex allowed us to pinpoint the main structural determinants of recognition of the C-terminal sequence of the E6 protein and the long-range perturbations induced upon PBM binding.

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Long-term warfarin therapy was changed to subcutaneous heparin to cover a planned pregnancy in a patient with congenital antithrombin III (AT III) deficiency. Satisfactory anticoagulation was easily maintained in spite of low levels of biologically active AT III. Delivery and the puerperium were covered by a reduced dose of heparin and alternate day infusions of AT III concentrate. A mean dose of 0.77 U/kg of AT III concentrate produced a rise of 1% in AT III and the half-life was of the order of 24 h, with no evidence of increased consumption during labour and delivery. Pregnancy and labour were uncomplicated and resulted in delivery of a healthy female infant. The importance of early and adequate anticoagulation during pregnancy is emphasized.

Summary High-dose etoposide (2.0-2.4 g m-2) with granulocyte colony-stimulating factor (G-CSF) is an effective strategy to mobilize perpheral blood progenitor cells (PBPCs), although in some patients this is associated with significant toxicity. Sixty-three patients with malignancy were enrolled into this non-randomized sequential study. The majority (55/63, 870,o) had received at least two prior regimens of chemotherapy. and seven patients had previously failed to mobilize following high-dose cyclophosphamide with G-CSF. Consecutive patient groups received etoposide at three dose levels [2.0 g m-2 (n = 22). 1.8 g m-2 (n = 20) and 1.6 g m-2 (n = 21)] followed by daily G-CSF. Subsequent leukaphereses were assayed for CD34-cell content, with a target total collection of 2.0 x 106 CD34-cells kg-'. Toxicity was assessed by the development of significant mucositis. the requirement for parenteral antibiotics or blood component support and rehospitalization incidence. Ten patients (169o) had less than the minimum target yield collected. Median collections in the three groups were 4.7 (2 g m-2). 5.7 (1.8 g m-2) and 6.5 (1.6 g m-2) x 106 CD34-cells kg-'. Five of the seven patients who had previously failed cyclophosphamide mobilization achieved more than the target yield. Rehospitalization incidence was significantly lower in patients receiving 1.6 g m-2 etoposide than in those receiving 2.0 g m-2 (P = 0.03). These data suggest that high-dose etoposide with G-CSF is an efficient mobilization regimen in the majority of heavily pretreated patients, including those who have previously failed on high-dose cyclophosphamide with G-CSF. An etoposide dose of 1.6 g m-2 appears to be as effective as higher doses but less toxic.

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