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The abyssal ocean is broadly characterized by northward flow of the densest waters and southward flow of less-dense waters above them. Understanding what controls the strength and structure of these interhemispheric flows-referred to as the abyssal overturning circulation-is key to quantifying the ocean's ability to store carbon and heat on timescales exceeding a century. Here we show that, north of 32° S, the depth distribution of the seafloor compels dense southern-origin waters to flow northward below a depth of about 4 kilometres and to return southward predominantly at depths greater than 2.5 kilometres. Unless ventilated from the north, the overlying mid-depths (1 to 2.5 kilometres deep) host comparatively weak mean meridional flow. Backed by analysis of historical radiocarbon measurements, the findings imply that the geometry of the Pacific, Indian and Atlantic basins places a major external constraint on the overturning structure. [ABSTRACT FROM AUTHOR]

HER-2/neu is a tumour antigen that is overexpressed in human breast tumours. Among the vaccine strategies developed to overcome immune tolerance to self-proteins, vaccination with anti-idiotypic (anti-Id) antibodies has been described as a promising approach for treatment of several malignant diseases. To develop an active immunotherapy for cancer patients positive for HER-2/neu, we investigated immunisation with human anti-Id single-chain fragments (scFv) mimicking the conformation of HER-2/neu protein to induce a humoral response in mice. We selected by phage display two human anti-Id scFv (Ab2β) directed against trastuzumab F(ab')2 fragments (Ab1), a humanised anti-HER-2/neu monoclonal antibody. Using competitive ELISA and Biacore biosensor analysis, we showed that anti-Id scFv 40 and scFv 69 could inhibit HER-2/neu binding to trastuzumab. Following vaccination of BALB/c mice with the soluble or phage-displayed scFv, Ab3 polyclonal antibodies, and among them Ab1' antibodies able to bind HER-2/neu, were detected in the sera of the immunised mice. These results demonstrate that the human anti-Id scFv could act as a surrogate antigen for HER-2/neu. The present study strongly suggests that the novel 30 kDa human mini-antibody could be used as an anti-idiotype-based vaccine formulation to induce an effective humoral response in patients bearing HER-2/neu-positive tumours. [ABSTRACT FROM AUTHOR]

Recent studies in human bone-marrow culture and healthy human volunteers suggest that lenograstim [glycosylated, recombinant human granulocyte colony-stimulating factor (rHuG-CSF) produced in Chinese hamster ovary (CHO) cells] has greater in vivo potency than filgrastim [nonglycosylated, methionine-extended recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF) produced in Escherichia coli]. To confirm and extend these results we investigated thein vivopotency of both products in normal rats and neutropenic CD rats as an animal model of chemotherapy-induced neutropenia. In normal rats, groups of eight normal male CD rats received four subcutaneous doses of 10, 30, or 100 μg/kg filgrastim or lenograstim on days 1 - 4 of the study, whereas a control group received the vehicle. Blood samples were collected from each animal before treatment (day - 5) and on days 2, 3, 5, 8, and 12 of the study for determination of red blood cell (RBC), platelet, white blood cell (WBC), and differential counts. rHuG-CSF and r-metHuG-CSF produced increased WBC counts, principally due to elevated absolute neutrophil counts (ANCs); on days 2, 3, and 5, all groups receiving rG-CSF had ANCs that increased in a progressive and dose-related manner. With the exception of a single value, mean ANCs obtained on days 2, 3, and 5 in lenograstim-treated groups were higher (statistically significant on day 3 at 30 and 100 μg/kg and on day 5 at 10, 30, and 100 μg/kg) than the respective values obtained in filgrastim-treated groups. No compound-related effect was noted in RBC or platelet parameters. Neutropenia was induced in male CD rats (12 animals/group) with a single intraperitoneal dose of 50 mg/kg cyclophosphamide (CPA) on day 0. On days 1 - 4, CPA-treated groups were treated with the vehicle (control) or with filgrastim or lenograstim at 30 or 100 μg/kg per day. An additional group was not treated with CPA and served as the absolute control group. Blood was collected from alternating subgroups on study day - 5 (pretest) and on days 2, 3, 4, 5, 6, 8, 9, and 12 for determination of RBC, platelet, WBC, and differential counts. No major adverse in-life effect was noted in neutropenic rats. Maximal depression of WBCs and ANCs occurred on day 5, followed by recovery to normal values by days 9 (ANC) and 12 (WBC). On day 3 and days 5 - 9, rHuG-CSF- and metHuG-CSF-treated groups had marked and dose-related increases in WBCs as compared with CPA-treated controls, principally due to elevated ANCs. With the exception of a few values, mean ANC values obtained in lenograstim-treated groups were consistently higher than the respective values obtained in filgrastim-treated groups; the difference was statistically significant on day 3 (30-μg/kg groups) and on days 6 and 8 (100-μg/kg groups). In conclusion, treatment of normal and neutropenic CD rats with lenograstim resulted in a dose-related elevation of ANCs that was consistently and significantly higher than the response to identical doses of filgrastim. These results suggest that lenograstim, the glycosylated form of rG-CSF, has superior in vivo potency in normal and neutropenic animals as compared with filgrastim, the nonglycosylated form of rG-CSF. [ABSTRACT FROM AUTHOR]