SUMMARY1. In pentobarbitone-anaesthetized cats, responses were recorded in peripheral nerves or cervical dorsal columns from sensory fibres associated with Pacinian corpuscle (P.c.) receptors in the forelimb footpads. Factors affecting the phase of response to cutaneous vibration in individual P.c. fibres, and the extent of phase coherence in the responses of different P.c. fibres were examined when sinusoidal vibratory stimuli at 100-400 Hz were delivered using a 1 mm diameter probe.2. Increases in vibration amplitude from the absolute to the 1 : 1 threshold for the P.c. fibre led to phase advances in the response, often of about 60 deg, in over 850 of fibres tested at 200 and 300 Hz, but further increases had little effect.3. Variations in stimulus position within the receptive field led to unpredictable changes in the response phase that ranged from minimal change to shifts of 180 deg. As the response phase was unrelated to the distance from the point of peak sensitivity it is likely that at high vibration frequencies ( > 100 Hz) the recruited population of P.c. fibres will respond over the whole range of phase angles.4. The calculated phase of spike initiation in different pairs of P.c. fibres that shared coincident points of best sensitivity on the skin ranged from near synchrony to maximum asynchrony indicating that there is little phase coherence even in the subpopulation of somatotopically related P.c. fibres recruited by high-frequency cutaneous vibration.5. Paired recordings from P.c. fibres within the cervical dorsal columns revealed a broad range of phase discrepancies in the responses of P.c. fibres to vibration at 200 and 300 Hz.6. Several hypotheses are considered to explain the known presence of phaselocked responses to high-frequency ( > 100 Hz) vibration in the central neurones of dorsal column nuclei.

SUMMARYWe examined the behaviour in vivo of native, specifically phosphorylated, and multimeric vitronectin to determine the effects of these modifications on its turnover, distribution and molecular behaviour. In normal rabbits, the plasma half-life (T 1/2 ) of antigenically detected vitronectin was 8 . 00 . In vitro, phosphorylation had no effect on the affinity of vitronectin for heparin-Sepharose, while complement activation with cobra venom factor (CVF) led to a two-fold enrichment of 32 P-vitronectin within the SC5b-9 complex. In vivo CVF caused a rapid decrease in the circulating levels of 32 P-vitronectin and was accompanied by the prompt appearance of a high mol. wt species consistent with SC5b-9. Despite specific incorporation of 32 P-vitronectin into SC5b-9, both forms of the molecule had similar inhibitory effects on C9-mediated haemolysis of EAC1-7 cells. Urea-activated vitronectin was rapidly cleared from circulation with less than 15% remaining after 1 h while protein-bound label accumulated in the spleen, lung and liver. These results demonstrate that vitronectin is a rapidly metabolized protein whose in vivo behaviour is markedly altered when phosphorylated or activated to form multimers and SC5b-9.

SUMMARYMany diseases associated wilh complement activation are characterized by tissue deposition of components of the terminal complement complex (TCC). The ninth component of complement (C9) plays an important role in the cytolytic effects, and may contribute to the non-lethal cellregulating functions ofthe TCC [1]. In this study we examined the behaviour of radiolabelled human C9 and its soluble complexed form SC5b-9 in vivo in order to determine the effects of complement activation on its turnover, distribution and molecular size. In normal rabbits the metabolic parameters of'^^I-C9 {median and range) were: plasma half-life (/[/2)25'9 (20-6 29-5) h, fractional catabolic rate (FCR) 5-7 (5'3-7'0)%/h. and extravascular/lntravascular ratio (EV/IV) 0'7 (0-6-11). The distribution of radiolabelled C9 amongst body tissues was similar to that observed for rabbit serum albumin (RSA). Activation ofthe complement cascade with i.v. injection of cobra venom factor (CVF) resulted in rapid disappearance of C9 from the plasma and accumulation of protein-bound radiolabel in the spleen (exceeding !he plasma concentration) and the liver. RSA metabolism and distribution were unaffected by CVF. Fine performance liquid chromatography (FPLC) gel filtration of plasma samples suggested that monomeric C9 was the only major radiolabelled protein present during normal turnovers, whereas CVF administration was accompanied by the prompt appearance of a high mol. wt species consistent in size with SC5b-9. When injected directly, '"^I-SC5b-9 disappeared rapidly from the plasma, falling by 50% in 0 7 (0-6-()-8) h, and less than 15% remaining after 4 h with accumulation of protein-bound label in the spleen and liver. These results demonstrate the complexity of C9 metabolism during complement activation.Keywords C9 terminal complement complex metabolic turnover tissue distribution SC5b-9

Fetal hematopoiesis is characterized by expanding erythropoiesis to support a continuously increasing RBC mass. To explore the basis for this anabolic, nonhomeostatic erythropoiesis, the proliferative effect of recombinant hematopoietic growth factors on highly enriched hematopoietic progenitor cells from fetal and adult tissues were compared. Fetal hepatic BFU-E, unlike adult bone marrow (BM) or peripheral blood (PB) BFU-E, were capable of proliferating in response to erythropoietin in the absence of added GM colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3), and erythropoietin (Epo) directly stimulated the expansion of the fetal BFU-E pool in suspension culture. A murine monoclonal antibody (MoAb), Ep 3, was raised against enriched fetal liver progenitor cells, which detected all fetal BFU-E and which reacted with the erythropoietin-responsive, GM-CSF/IL-3-independent fraction of adult BM BFU-E and CFU-E. All adult PB BFU-E were Ep 3- but became Ep 3+ after stimulation with GM-CSF or IL-3. These data indicate that Epo plays a unique role in fetal hepatic erythropoiesis, stimulating proliferation of immature BFU-E in addition to promoting terminal differentiation of later erythroid progenitor cells. In addition, these results demonstrate a MoAb which detects all erythropoietin-responsive progenitor cells and distinguishes the BFU-E compartments in adult BM and PB.