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Disaggregated embryonic yolk sac cells and circulating peripheral blood cells were obtained from normal murine day 9 embryos, prior to the formation of the fetal liver. These cells were microinjected transplacentally into days 11-15 W mutant anemic fetuses, when the fetal liver was the major hemopoietic organ. In a small proportion of the recipient animals examined after birth, long-term repopulation by the embryonic donor hemopoietic cells was observed. The donor hemopoietic stem cells proliferated and differentiated in the hosts as evidenced by the presence of donor hemoglobins in the growing recipient host animals. Some mothers of the pups were also repopulated by the donor stem cells. These results provide direct evidence that, during early murine embryogenesis, there are functional hemopoietic stem cells which are capable of colonizing the adult hemopoietic organs and probably the fetal liver and spleen to initiate hemopoiesis in these tissues.

3,4-Dihydroxy-5-fluorophenylalanine, fluorodopa, was injected into rats in which unilateral lesions of the nigrostriatal pathway had been made. The rats rotated towards the side with the lesions, thus providing further evidence that fluoro-dopa is an analogue of dopa. [18F]Fluoro-dopa was then injected intravenously into fully conscious baboons. A well-collimated scintillation detector, aligned along the occipitomental axis, recorded the accumulation of 18F in the brain. Control animals accumulated 18F continuously for 100 min. This accumulation represents net transport of [18F]fluoro-dopa from blood to brain, decarboxylation to [18F]fluoro-dopamine, storage, and degradation of [18F]fluoro-dopamine. α-Methyl-dopa, a competitive inhibitor of dopa transport and decarboxylation, prevented the accumulation of 18F; reserpine, known to release stored intracerebral dopamine, discharged 18F; pargyline, a monoamine oxidase inhibitor, and haloperidol, a known augmentor of intracerebral dopamine turnover, increased the rate of accumulation of 18F. These changes in the accumulation of intracerebral 18F, after [18F]fluoro-dopa, were commensurate with the known action of the drugs used to induce them and demonstrate the use of a γ-emitting precursor of a neurotransmitter to monitor simply, atraumatically, and externally the intracerebral metabolism of the transmitter in fully conscious primates. When applied to man, the same technique should be able to provide more conclusive evidence than is presently available for the role of catecholamines in schizophrenia and depression. It should also provide further insight into the natural history of nigrostriatal diseases and the action of drugs used in their treatment.

The projections of nerve fibres with immunoreactivity for the peptides enkephalin (ENK), gastrin-releasing peptide (GRP), neuropeptide Y (NPY), somatostatin (SOM), substance P (SP) and vasoactive intestinal peptide (VIP) were studied in canine small intestine by analysing the consequences of lesions of intrinsic and extrinsic nerves. Of peptides present in fibres supplying myenteric ganglia, GRP, SOM and VIP were in anally directed nerve pathways, whereas ENK and NPY were in orally directed pathways. Pathways ran for up to about 30 mm. SP fibres ran for short distances in both directions in the myenteric plexus. The circular muscle was supplied with ENK, NPY, SP and VIP fibres arising from the myenteric ganglia, whereas most mucosal SP and VIP fibres were deduced to arise from submucous ganglia. There were projections of fibres reactive for ENK, GRP, SOM, SP and VIP from myenteric ganglia to submucous ganglia. Antibodies to tyrosine hydroxylase were used to locate noradrenaline nerve fibres supplying the intestine; these fibres all disappeared when extrinsic nerves running through the mesentery to the small intestine were cut. It is deduced that there is an ordered pattern of projections of peptide-containing fibres in the canine intestine.

The ovarian enzyme 3α-hydroxysteroid dehydrogenase (3α-HSD) converts dihydrotestosterone (DHT) to 5 α-androstan-3α,17β-diol (3α-diol), a reduced androgen that does not bind to the granulosa cell androgen receptor. To determine the relative contribution of the granulosa cells to total ovarian 3α-HSD activity, adult rats treated with either medroxyprogesterone acetate (MPA) or vehicle underwent ovarian microdissection. 3α-Hydroxysteroid dehydrogenase is primarily located in excised follicles and corpora lutea, and is inhibited in the follicles but not corpora lutea by MPA (P< 0.05). Elimination of healthy granulosa cells while maintaining healthy theca cells by irradiation of the exteriorized ovaries with 6000 rads resulted in a marked reduction in 3α-HSD to 19% of control levels on a per-organ basis (P< 0.01). The granulosa cell is the major ovarian site for 3α-hydroxylation of ring A-reduced C19 steroids in the adult rat.

A method of measuring bone blood flow has been developed using 18F sodium fluoride and positron emission tomography. The blood flow levels are in line with those obtained experimentally from microsphere embolisation. This investigative method could be applied to elucidate a number of clinical questions involving bone perfusion.