The effects of hypoxemia with progressive acidemia on fetal renal function in sheep

In order to determine the effects of fetal hypoxemia on renal blood flow, glomerular filtration rate (GFR) and urethral and urachal urine output, we examined the effects of 3 h maternally-induced (9% O2, 3% CO2, 88% N2) fetal hypoxaemia on 10 chronically-instrumented fetal sheep between 127-135 days of gestation. Fetal arterial pH fell significantly during the second and third hours of hypoxia and this coincided with a significant increase in fetal arterial blood pressure (P less than 0.05). During the second hour of hypoxia, with mild acidaemia, fetal GFR decreased significantly and then, during the third hour, fetal GFR, urethral and total urine output were significantly elevated. During the 2-h recovery period urachal and total, but not urethral urine output, were significantly elevated (P less than 0.05). The data suggested that the increase in GFR and urine output measured during the third hour of hypoxia and the recovery period may reflect a pressure diuresis.     

The influence of an elastic tendon on the force producing capabilities of a muscle during dynamic movements

With increasing computer power, computer simulation of human movement has become a popular research tool. However, time to complete simulations can still be long even on powerful computers. One possibility for reducing simulation time, with models of musculo-skeletal system, is to simulate the muscle using a rigid tendon rather than the more realistic compliant tendon. This study examines the effect of tendon elasticity on muscle force output under different dynamic conditions. A single muscle, point mass model was used and simulations were performed varying the mass, the tendon length, the initial position, and the task. For simulations for relatively slow motion, as experienced for example in upper limb reaching motions or rising from a chair, tendon properties had little influence on muscle force, in contrast simulations of an explosive task similar to jumping or throwing tendon had a much larger effect.     

Administration of extra-amniotic arachidonic acid and the suppression of uterine prostaglandin synthesis during pregnancy in the rhesus monkey.

After extra-amniotic treatment of pregnant rhesus monkeys premature parturition was induced in 4 given 2.5 mg PGE-2; none of the 4 monkeys given 100 mg arachidonic acid were affected. The concentrations of PGE, PGF, or 13,14-dihydro-15-oxo-PGF did not change after arachidonic acid treatment, but all increased after PGE-2. It is suggested that the availability of substrate, arachidonic acid, is not a major factor governing the control of PG synthesis but that the latter is suppressed during pregnancy.     

Preadministration of a T-suppressor factor enhances tumor immunity in DBA/2 mice

Summary Human peripheral blood mononuclear cells (PBM) activated with recombinant interleukin-2 (IL-2) generate potent lytic activity (LAK) against a variety of malignant cells. IL-2 alone is sufficient for LAK generation, but high concentrations are needed to generate optimal cytotoxicity. Our recent studies based on combinations of biological agents indicated that alternative activation pathways may exist. Synergy for LAK induction was investigated using IL-2 and tumor necrosis factor- (TNF). Single-cell suspensions of primary human lung carcinomas were prepared from seven established cell lines and 32 fresh tumor specimens. Not only were all cell lines sensitive to allogeneic LAK, but also all fresh tumors were sensitive to some degree to both autologous and allogeneic LAK lysis measured by a 4-h ⁵¹Cr-release assay. LAK-mediated cytotoxicity, induced with a combination of human recombinant IL-2 (Cetus, 100 U/ml) and TNF (Genentech, 500 U/ml), showed a mean fourfold increase (range 0.7–16.3) over IL-2 alone. No lytic activity was generated from PBM incubated with media or TNF alone. The sequence dependence of adding IL-2 and TNF in enhancing cytolytic activity was also studied. In vitro kinetics data revealed that the addition of TNF 2–6 h before the addition of IL-2 greatly increased LAK activity over that obtained from the simultaneous addition of the two cytokines. These results demonstrated (a) the synergy of IL-2 and TNF for generating LAK; (b) the lysis of fresh primary lung cancer cells by LAK; and (c) the sequence dependence of IL-2 and TNF for the induction of optimal LAK activity.This work was supported by NCI Grants RO2-CA45225 and CAO 9611-01, and by an award from the Prouss Foundation     

Suppressor deletion therapy: selective elimination of T suppressor cells in vivo using a hematoporphyrin conjugated monoclonal antibody permits animals to reject syngeneic tumor cells

Summary A MAb (B16G) which recognizes a constant epitope on TsC and their soluble factors in DBA/2 mice has been described previously. In this study, we show that when this MAb is covalently linked to the photoactivable molecule Hp, and injected i.v. into P815 tumor-bearing mice which were subsequently exposed to light, tumors undergo permanent regression in 10%–40% of these mice (depending on the individual experiment). All control animals died within an average of 22–24 days after tumor cell injection. It is suggested that tumor regression is attributable to immune mechanisms facilitated by the elimination of a population of TsC. When splenocytes of B16G-Hptreated mice were assayed in vitro for the generation of CTL active against P815 tumor cells, it was found that 24 h after treatment, a significant increase in killer cell activity was noted but that this effect was gone by 48h. We also show that B16G-Hp conjugates are capable in vitro of specifically killing cells of a TsC hybridoma, A10 (which has been shown previously to secrete a T suppressor factor reactive with P815 cell surface antigens). This conjugate had no cytotoxic effect on P815 cells under conditions in which A10 cells were killed.Abbreviations CTL cytotoxic T lymphocytes - C-MAb control monoclonal antibody - EDCI 1-ethyl-3-(3-diemthylaminopropyl) carbodiimide - Hp hematoporphyrin - MAb monoclonal antibody - PBS phosphate-buffered saline - RMIg rabbit antimouse Ig - TsC T suppressor cell - TsF T suppressor factor - FCS fetal calf serum - DME Dulbecco's modified Eagle's medium     

The phylogeographical clade trade: tracing the impact of human-mediated dispersal on the colonization of northern Europe by the oak gallwasp Andricus kollari

Human dispersal of organisms is an important process modifying natural patterns of biodiversity. Such dispersal generates new patterns of genetic diversity that overlie natural phylogeographical signatures, allowing discrimination between alternative dispersal mechanisms. Here we use allele frequency and DNA sequence data to distinguish between alternative scenarios (unassisted range expansion and long range introduction) for the colonization of northern Europe by an oak-feeding gallwasp, Andricus kollari. Native to Mediterranean latitudes from Portugal to Iran, this species became established in northern Europe following human introduction of a host plant, the Turkey oak Quercus cerris. Colonization of northern Europe is possible through three alternative routes: (i) unassisted range expansion from natural populations in the Iberian Peninsula; (ii) unassisted range expansion from natural populations in Italy and Hungary; or (iii) descent from populations imported to the UK as trade goods from the eastern Mediterranean in the 1830s. We show that while populations in France were colonized from sources in Italy and Hungary, populations in the UK and neighbouring parts of coastal northern Europe encompass allozyme and sequence variation absent from the known native range. Further, these populations show demographic signatures expected for large stable populations, rather than signatures of rapid population growth from small numbers of founders. The extent and spatial distribution of genetic diversity in the UK suggests that these A. kollari populations are derived from introductions of large numbers of individuals from each of two genetically divergent centres of diversity in the eastern Mediterranean. The strong spatial patterning in genetic diversity observed between different regions of northern Europe, and between sites in the UK, is compatible with leptokurtic models of population establishment.     

Mechanisms for incorporation of glycerol-derived precursors into polyketide metabolites

Several polyketide secondary metabolites are shown by feeding experiments to incorporate glycerol-derived 3-carbon starter units, 2-carbon extender units, or 3-carbon branches into their hydrocarbon chains. In recent years, genetic studies have begun to elucidate the mechanisms by which this occurs. In this article we review the incorporation of glycerol-derived precursors into polyketides and propose new mechanisms for the incorporation processes. Laura J. Walton, Christophe Corre contributed equally to this article