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Anti-NMDAR encephalitis is a newly characterized syndrome with a progressive, predictable clinical course and the possibility of effective treatment. Accurate and timely diagnosis is critical to selection and implementation of treatments, and optimal patient outcomes. Outcomes are improved with early diagnosis via indirect immunofluorescence or cell-based assays, and the rapid and appropriate administration of immunosuppressant and anti-psychotic therapies. Three possible scenarios accounting for the immunopathogenesis of anti-NMDAR encephalitis are presented, with the most probable one being that of paraneoplastic autoimmunity. Future efforts in this disorder should focus on elucidating the mechanisms that contribute to initiation of this antibody response, as well as exploring the role of tumors, infectious triggers and immune-reactivation. Finally, accessible tools need to be developed that allow for reliable identification of specific antibody markers against synaptic proteins., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The reproducibility of various procedures for the noninvasive assessment of the skeleton in dogs has been measured. In one animal, dual photon measurements of bone mineral mass were made in the whole body, the lumbar spine, and the proximal femur on 10 occasions during a 15-week period. In two other dogs, repeat measurements of Tc-99m imidodiphosphate (IDP) retention were made. For the total body and the proximal femur, the reproducibilities were 2 and 2.5%, respectively. The reproducibility of the lumbar spine was approximately 10% and was influenced by the variable fraction of the posterior spinous processes included in the measurement. The reproducibility of IDP retention measurements was not established. It was about 8% when all 10 measurements were considered but fell to 1.5% when three consecutive measurements were excluded. Dual photon measurements of the whole body and the proximal femur can be used to assess bone mass changes in the canine skeleton.

Rabies continues to be a serious problem in both developed and developing nations due to the reservoir of rabies virus in wildlife vectors. The control and worldwide eradication of rabies depends on the development of safe, effective, and economical vaccines that might be used in preexposure vaccination programs for humans and animals. To this end an infectious human adenovirus type 5 recombinant virus that contains the rabies glycoprotein gene, and which may serve as the prototype for a new class of vaccines against rabies, was constructed and tested. This recombinant, when administered by either the parenteral or oronasal route, was highly effective in eliciting good levels of rabies-neutralizing antibodies in the sera of dogs and mice. Mice immunized by the recombinant virus were protected from lethal intracerebral challenge with rabies virus.

The role of intrinsic nerves in the control of migrating myoelectric complexes (MMCs) was studied in seven conscious dogs, each implanted with a set of eight bipolar Trimel wire electrodes. Local areas, 3-5 cm long, were perfused close intra-arterially via an exteriorized heparinized Silastic cannula. Experiments consisted of giving bolus injections of atropine (20-50 micrograms), hexamethonium (20 mg), and tetrodotoxin (TTX; 3-30 micrograms) via the catheter at varying periods of time with respect to the arrival of phase III at the perfused site. Atropine and hexamethonium, given close intra-arterially immediately before the arrival of phase II at the perfused site, blocked its further propagation. Tetrodotoxin given locally also blocked the propagation of phage III, as above. After the block, TTX initiated a new phase III activity at, or distal to, the perfused site in 10 out of 14 perfusions. The new phase III activity propagated distally. This study shows that the mechanisms for the initiation and propagation of MMCs are built into the enteric plexus. Once an MMC is initiated, its propagation is achieved by proximal-to-distal excitation through the intrinsic cholinergic network of neurons. This study explains the lack of any significant changes in the propagation parameters of MMCs after vagotomy or celiac and superior mesenteric ganglionectomy.

The inadvertent extravasation of anticancer drugs in clinical use may result in the development of indolent lesions at the site of injection. Investigation of this phenomenon in Hartley guinea pigs showed that the pathogenesis was based on direct tissue toxicity and not on sensitization. The risk of a serious reaction appeared to be related to the localization of the injurious agent within the dermis rather than at the subcutaneous site.

Morphine was injected intravenously at various phases of the migrating myoelectric complex (MMC) cycle to study the oscillatory characteristics of MMCs by the premature initiation of phase IIIs. All injection timings were represented as a percentage of the normal MMC period at the most proximal duodenal electrode. During the initial 20% of the MMC cycle, the mechanism of initiation of MMCs was in an absolutely refractory state in the sense that a supramaximal dose of morphine (200-300 micrograms/kg) did not initiate a premature phase III. During the remainder of the MMC cycle, the control mechanism was in a relatively refractory state. As this state progressed, premature phase III activity was initiated with diminishing doses of morphine. This was called the relatively refractory state. The initiation of a premature phase III by morphine did not affect the phase III already in progress, except that its propagation velocity was increased. Truncal vagotomy did not affect the refractory characteristics of MMCs or the action of morphine. Only large doses of naloxone (2 mg/kg) blocked the above action of morphine. The study shows that the MMC cyclic phenomenon has the characteristics of relaxation oscillators that may result from enteric neural biological clocks. The period of these oscillators can be altered by stimulants such as morphine.

The ovarian enzyme 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD) converts dihydrotestosterone (DHT) to 5 alpha-androstan-3 alpha,17 beta-diol (3 alpha-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 3 alpha-HSD activity, adult rats treated with either medroxyprogesterone acetate (MPA) or vehicle underwent ovarian microdissection. 3 alpha-Hydroxysteroid dehydrogenase is primarily located in excised follicles and corpora lutea, and is inhibited in the follicles but not corpora lutea by MPA (P less than 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 3 alpha-HSD to 19% of control levels on a per-organ basis (P less than 0.01). The granulosa cell is the major ovarian site for 3 alpha-hydroxylation of ring A-reduced C19 steroids in the adult rat.

A subacute toxicity study on 99m Tc stannous glucoheptonate was performed with rats, dogs and rabbits, injected intravenously at ten to 100 times the human dose on a body weight basis. There were no abnormalities in the clinical status of any of the animals. No changes were found in urinalysis, blood chemistry or hematology in the rabbit nor in gross examination, renal histology or bone marrow smears in the rats and rabbits. Hepatic histology was also done. A focal area of necrosis in a liver of one rabbit that had been injected with 100 times the human dose was observed using light microscopy. Examination by electron microscopy in another group of rats and rabbits was prompted by the observation of that lesion. This revealed vacuolated and dilated smooth endoplasmic reticulum and degranulated and vesiculated rough endoplasmic reticulum in all the test livers. X-ray microanalysis indicates that the ultrastructural changes are linked to the deposition of tin.

Test doses (0.5 ml) of the perfluorochemical blood substitute Fluosol-DA causes pulmonary hypertension in some patients. To investigate this phenomenon we infused Fluosol-DA into unanesthetized sheep with chronic vascular catheters on ten occasions. In six of these experiments lung lymph flow was measured. Since other fluorochemical blood substitutes alter the coagulation cascade we also sampled blood to perform coagulation screening tests and look for evidence of thrombin generation as assessed by the survival of 125I labelled sheep fibrinogen. Test doses (0.5 ml) of Fluosol-DA resulted in transient but marked pulmonary hypertension in nine of ten experiments (17 +/- 1.2 SE to 43 +/- 3.9 SE torr). Cardiac output decreased by an average of 30%, and lung lymph flow transiently increased without a change in the lymph to plasma protein concentration (L/P) ratio in five of six experiments. When 50 ml of Fluosol-DA was administered one hour later the pulmonary hypertension was more prolonged but less severe (18 +/- 1.0 SE to 34 +/- 3.2 SE torr). Lymph flow again increased without a change in the L/P ratio for protein. The activated partial thromboplastin and prothrombin times, and survival in plasma of 125I labelled sheep fibrinogen were unaffected by administration of Fluosol-DA. We conclude that Fluosol-DA causes pulmonary hypertension in sheep and increases lung lymph flow. This results from vasoconstriction of the pulmonary vessels and subsequent recruitment of the pulmonary microvasculature and not from thromboembolic phenomena.

An infectious recombinant human adenovirus type 5 (Ad5) vector, AdG12, which carries the glycoprotein gene of vesicular stomatitis virus (VSV) and expresses that gene in cultured HeLa cells was used to examine the host range of insert expression by human Ad vectors. The VSV glycoprotein was expressed in bovine, canine and murine cells when infected with AdG12 in culture. These cell lines are respectively permissive, non-permissive and semi-permissive for human Ad5 replication. Administration of the AdG12 vector to calves, piglets or dogs by either the subcutaneous or oral route resulted in the production of high titres of neutralizing antibodies to VSV. Mice injected intraperitoneally with the vector produced neutralizing antibodies and were protected against subsequent intravenous challenge with normally lethal doses of VSV. This work demonstrates the utility of human adenoviral vectors for antigen expression in a number of non-human cell lines and for the induction of an immune response to the delivered antigen in a number of species.

In previous experiments it was shown that repeated mechanical or immunologic injury to the arterial intima of normally fed rabbits induced lesions morphologically identical with human atherosclerosis. These regressed in size and lipid content when the injury stimulus was removed. By contrast, repeated injury directed to removal of only the endothelial layer induced lesions in which lipid accumulated in areas of endothelial regeneration and increased with time. In the present report the lesions associated with multiple and with a single episode of endothelial removal, using a Fogarty balloon catheter, are compared. Lipid accumulates in areas of endothelial regrowth following one endothelial injury and is similar in amount to that at comparable time intervals following the first of multiple balloon removals of the endothelium. There is much more lipid in areas of endothelial regrowth than in areas that remain uncovered by endothelium, the lipid tends to increase with time, and there is more lipid in the abdominal aortic than in the thoracic aortic lesions. A correlation was found between lipid content and thickness of lesions, especially in response to multiple removals of the endothelium. Multiple removals resulted in thicker lesions than a single injury. There appeared to be a positive relationship between the level of blood cholesterol and the amount of lipid deposited in areas of endothelial regrowth. This is consistent with trapping of low density lipoprotein by glycosaminoglycans in the neointima covered by regenerated endothelium.

There is increasing interest in the effects of environmental and therapeutic agents on the reproductive system, in particular, the ovary. To study the effects of controlled doses of ionizing radiation to the ovary, Sprague-Dawley rats had their ovaries exteriorized and subjected to increasing doses of radiation. There was a significant increase in ovarian follicular atresia, a significant increase in serum follicle-stimulating hormone levels, but no change in serum luteinizing hormone levels. This experimental protocol may facilitate the testing putative radioprotectants.

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.

Tissue wet weight as well as total protein content, 5'-nucleotidase activity, alkaline phosphatase activity and Ca2+ accumulation associated with a plasma membrane fraction isolated from spontaneous hypertensive rats (SHR) and rats with deoxycorticosterone (DOC) induced hypertension were investigated. Enhanced alkaline phosphatase activity and reduced ATP-dependent Ca2+ accumulation preceded the development of hypertension in SHR and these effects were reversed by DOC withdrawal followed by lowering of blood pressure in DOC hypertension. Increased arterial tissue wet weight and 5'-nucleotidase occurred only at the later stage of hypertension in SHR and the increased tissue wet weight was not reversed by DOC withdrawal in DOC hypertension. These observations suggest that enhanced alkaline phosphatase and reduced ATP-dependent Ca2+ uptake may play a significant role in initiating hypertension, while increased arterial wet weight and 5'-nucleotidase activities may participate in the maintenance of hypertension.

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.

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.

The use of autogenous vein as an arterial substitute has been advocated for many years. Methods of harvesting generally cause spasm of the vein and it has been shown that preventing the spasm by applying papaverine improves long-term patency. The present study was undertaken to see if the reported long-term patency of such grafts was associated with improved short-term appearance of the venous endothelium as viewed with the scanning electron microscope. Two groups of dogs were studied; those sacrificed at 3 hours and those at 24 hours after replacing excised segments of the carotid and femoral arteries with cephalic veins. One of the veins was removed in the standard manner allowing spasm followed by distension back to its pre-spasm state; in the other, spasm was prevented by the topical application of papaverine before removal. The study shows that venous endothelial integrity is preserved by the use of papaverine and this improved appearance of the endothelium persists for the first 24 hours after insertion into an arterial milieu. But the study also demonstrated that there was extensive activity of polymorphonuclear leukocytes associated with the endothelium in the early hours after arterialization and that they appeared to have a deleterious effect on the endothelium.

We investigated the effects of a partial compared to a complete thrombotic occlusion of the left anterior descending coronary artery in dogs. A completely occlusive thrombus was associated with a full thickness myocardial infarction. Mural thrombus was associated with focal areas of myocardial injury, mainly subendocardial in location. The findings are compatible with the concept that mural thrombus can give rise to platelet or platelet-fibrin emboli in the microcirculation which cause focal areas of ischemic damage. This pathogenesis was further explored using a thrombogenic wire placed in the left anterior descending coronary artery by indirect technique. Five of 10 dogs had developed a completely occlusive thrombus, whereas five had a mural thrombus at death, which occurred within 2 days. Three of the five dogs with mural thrombus had focal ischemic myocardial damage and platelet-fibrin thrombi; the other two that died early showed only platelet fibrin masses in the microcirculation. When platelets were labeled with 111Indium, there was increased radioactivity in the territory of the myocardium served by the artery containing a developing thrombus.

In order to determine whether the ovarian follicles of the domestic cat which normally ovulates following copulation, were similar to those of the rabbit steroidogenically, the following experiments were carried out. Follicles were dissected out of ovaries from nine estrous cats throughout the year and incubated in medium alone or with luteinizing hormone (LH) or human chorionic gonadotropin (HCG). Media were removed every 15 min and stored frozen until analyzed for testosterone using established radioimmunoassay procedures. Although LH and HCG caused slight increases in testosterone production the amounts produced were much less than that produced by rabbit follicles under identical conditions. However, when follicles were incubated for a total of 8 h without removal of media, marked changes in testosterone and estradiol production occurred. These data suggest that the ovarian follicles of the estrous cat are steroidogenically active.

Intraperitoneal (IP) administration of the glutaramic acid derivative proglumide inhibited satiety induced by all IP doses of cholecystokinin octapeptide (CCK-OP) in 3-hour food-deprived intact rats. Proglumide did not influence satiety when administered alone and did not inhibit satiety induced by IP glucagon. While proglumide did not inhibit satiety induced by low doses of IP bombesin, it partially and significantly inhibited the satiety effects produced by high doses of this peptide. Since bombesin is a known secretagogue for CCK in several species, these results indicate that while bombesin and CCK act independently to induce satiety, the effect induced by high doses of bombesin is mediated, in part, by the release of endogenous CCK or a structurally related peptide. Furthermore, these results illustrate that proglumide is a specific antagonist of CCK-induced satiety and is, therefore, a potentially useful tool for investigating the physiologic role of this peptide in the control of food intake.

To assess the effects of a gonadotropin-releasing hormone agonist, [D-Leu6,des-Gly10] luteinizing hormone-releasing hormone ethylamide, in ameliorating the damage caused by ionizing radiation, gonadotropin-releasing hormone agonist was administered to rats from day 22 to 37 of age in doses of 0.1, 0.4, and 1.0 microgram/day or vehicle and the rats were sacrificed on day 44 of age. There were no effects on estradiol, progesterone, luteinizing, or follicle-stimulating hormone, nor an effect on ovarian follicle numbers or development. In separate experiments, rats treated with gonadotropin-releasing hormone agonist in doses of 0.04, 0.1, 0.4, or 1.0 microgram/day were either irradiated or sham irradiated on day 30 and all groups sacrificed on day 44 of age. Irradiation produced a reduction in ovarian weight and an increase in ovarian follicular atresia. Pretreatment with the agonist prevented the reduction in ovarian weight and numbers of primordial and preantral follicles but not healthy or atretic antral follicles. Such putative radioprotection should be tested on actual reproductive performance.

We have validated a radiochemical technique for measuring the rate of secretion of plasma triglycerides from the liver and/or splanchnic region during the consumption of glucose under isotopic steady-state conditions. Values obtained with this technique correlated closely with those based on transhepatic or transsplanchnic chemical gradients (r = 0.95). Likewise, values for secretion of triglycerides obtained with the radiochemical technique correlated closely with those obtained for extrahepatic or extrasplanchnic triglyceride clearance. Values for mean net splanchnic and hepatic secretion of plasma triglyceride fatty acids, transported essentially in very low density lipoproteins, were 1.9 and 2.0 mumoles/min.kg body wt0.75, respectively, about one-half of the rate of transport of free fatty acids. However, the fraction of triglyceride fatty acids of plasma very low density lipoproteins that was derived from plasma free fatty acids averaged 9% and that derived from glucose, though increasing with time, reached only 2% after constant intravenous infusion of radioglucose for 5 hr. Porcine hepatic secretion of plasma triglycerides is large in the glucose-fed state, and the secreted triglyceride fatty acids evidently are derived from stored fat or glycon.

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. [(18)F]Fluoro-dopa was then injected intravenously into fully conscious baboons. A well-collimated scintillation detector, aligned along the occipitomental axis, recorded the accumulation of (18)F in the brain. Control animals accumulated (18)F continuously for 100 min. This accumulation represents net transport of [(18)F]fluoro-dopa from blood to brain, decarboxylation to [(18)F]fluoro-dopamine, storage, and degradation of [(18)F]fluoro-dopamine. alpha-Methyl-dopa, a competitive inhibitor of dopa transport and decarboxylation, prevented the accumulation of (18)F; reserpine, known to release stored intracerebral dopamine, discharged (18)F; pargyline, a monoamine oxidase inhibitor, and haloperidol, a known augmentor of intracerebral dopamine turnover, increased the rate of accumulation of (18)F. These changes in the accumulation of intracerebral (18)F, after [(18)F]fluoro-dopa, were commensurate with the known action of the drugs used to induce them and demonstrate the use of a gamma-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.

Mature dogs were vaccinated with a myxovirus vaccine. At this time, half of the dogs were also given a subcutaneous injection of levamisole hydrochloride (2.2 mg/kg). Blood platelets were counted daily. The dogs that had received only the vaccine showed, after 48 hours, a 48% decrease in platelets. Levamisole reduced the thrombocytopenia associated with myxovirus vaccination. Levamisole could have a protective effect on platelets by preventing their aggregation induced by viral neuraminidase.

The effects of radiation and chemotherapy on gonadal function are relevant to the morbidity induced by such treatments. Cyclophosphamide given i.p. to rats on Day 30 of age delayed vaginal opening, prevented vaginal cyclicity, and caused a reduction in serum estradiol and progesterone. Antral follicular atresia increased in a dose-dependent fashion in response to cyclophosphamide (0 mg/kg, 53.5%; 1 mg/kg, 67.3%; 50 mg/kg, 65.7%; 100 mg/kg, 73.9%; 150 mg/kg, 92.2%). Despite such alterations in ovarian function, serum gonadotrophins did not rise. The concurrent administration of 0, 20, 30, 40, 50, and 60 Gy of radiation to the exteriorized ovaries in rats receiving 50 mg/kg cyclophosphamide induced widespread loss of primordial, preantral, and healthy antral follicles associated with reduction in serum progesterone and estradiol. Such irradiation induced dose-related increases in serum follicle-stimulating hormone and luteinizing hormone. Parenteral cyclophosphamide and local irradiation appear to induce ovarian toxicity by different mechanisms.

We measured pulmonary artery (Ppa) and left atrial (Pla) pressures, lung lymph flow, and lymph/plasma protein concentrations in four adult sheep at a barometric pressure of 380 Torr (1 Torr = 133.322 Pa) for 22 h. Hypobaric hypoxia caused an immediate increase in Ppa from 20 to 39 Torr. There was no significant change in Pla, lymph flow, or lymph protein concentrations. We conclude that hypobaric hypoxia does not affect lung fluid or protein exchange in awake adult sheep at rest.

Protein content, enzymatic activites and Ca2+ accumulation capacities were studied in plasma membrane fractions isolated from mesenteric arteries of rats made hypertensive by renal artery stenosis with and without contralateral nephrectomy, i.e., one-kidney, one clip (1-KHR) and two-kidney, one clip (2-KHR) hypertension, respectively. Both types of renovascular hypertension showed similar vascular plasma membrane abnormalities which included increased total protein contents, enhanced alkaline phosphatase activities and reduced ATP-dependent Ca2+ accumulation compared to control values. The altered alkaline phosphatase activity and ATP-dependent Ca2+ accumulation appeared to be associated with blood pressure elevation in both types of hypertension and may be related to the elevation of blood pressure insensitive to captopril (SQ 14,225) in 1-KHR and 2-KHR. These results are consistent with the current concept of biochemical abnormalities of arterial smooth muscle in the development ostem.

To study the efficacy of topically administered thrombin as an adjuvant in tubal microsurgery, 24 rabbits underwent a 1-cm resection and microsurgical anastomosis of both fallopian tubes and were randomized to either thrombin or cautery for hemostasis. Ovarian wedge biopsies were done on the left ovary. The animals were mated 4 to 5 weeks postoperatively with a buck of proven fertility. They were killed at 2 to 3 weeks' gestation to note the number of fetuses per patent tube and presence or absence of pelvic adhesions. There was no effect of topical thrombin on the crude pregnancy rate but it was associated with a marked reduction in the number of fetuses per patent tube, despite similar rates of pelvic adhesions between groups. Topically administered thrombin appeared to reduce fertility in this experimental model by an undefined mechanism.

This study compares the effects on intimal hyperplasia of different methods of manipulating a vein graft before using it as an arterial substitute. Grafts that were denuded of endothelium showed the most intimal hyperplasia, while those that were washed with saline, dilated with saline or crushed did not differ appreciably from each other with respect to the degree of intimal hyperplasia. The hyperplasia was well developed and stabilized at 3 weeks, which coincided with restoration of the endothelial surface. The similarity between the last three methods of graft manipulation suggests that minor endothelial disruption produced at the time of harvesting the vein is equalized after insertion of the vein into the arterial circulation.

[18F]fluoro-dopa, DL-3,4-dihydroxy-5-[18F]fluorophenylalanine, a tracer for dopa, was injected intravenously into cynomolgus monkeys anesthetized with enflurane, and the appearance of 18F in the head and the disappearance of 18F from the blood were each measured continuously for 10 min with simple gamma-ray detectors. A three-compartment explanatory model was used to derive fractional rate constants for the forward flux of L-dopa into the endothelium of the brain capillaries from the blood (1.54 +/- 0.37 min-1), the back flux of dopa and/or its metabolites to the blood from the endothelium (0.67 +/- 0.05 min-1), the formation of dopamine from dopa (0.20 +/- 0.04 min-1), and the destruction of dopamine (0.04 +/- 0.02 min-1). It was also shown that only one-fifth of the dopa that entered the endothelium was available for dopamine synthesis in neurons. It was concluded that the technique described could be extended to man and used to investigate the role of dopa and dopamine in the control of mood and locomotion.