Ornithine and histidine decarboxylase activities in mice sensitized to endotoxin, interleukin-1 or tumour necrosis factor by D-galactosamine. 1. An injection of D-galactosamine (GalN) into mice together with a lipopolysaccharide (LPS or endotoxin), interleukin-1 (IL-1) or tumour necrosis factor (TNF), sensitized the mice and induced fulminant hepatitis with severe congestion resulting in rapid death. Since LPS and these cytokines induce ornithine decarboxylase (ODC) and histidine decarboxylase (HDC) in the liver and spleen of mice, the effects of GalN on the induction of ODC and HDC in these organs were examined. 2. The induction of ODC by LPS, IL-1 or TNF was suppressed by GalN in the liver, and this suppression preceded the hepatic congestion. There was good agreement between the degree of hepatic congestion and the suppression of ODC induction by various amounts of GalN. The induction of ODC in the spleen was suppressed only at the highest dose of GalN examined. 3. GalN is known to deplete uridine 5'-triphosphate (UTP), resulting in the suppression of RNA and protein synthesis. An injection of uridine, the precursor of UTP, diminished the GalN-induced suppression of ODC induction by LPS and prevented the hepatic congestion and death. 4. LPS-pretreatment before injection of LPS plus GalN prevented the suppression of ODC activity and prevented the hepatic congestion and death. 5. An injection of putrescine, the product of ODC, prolonged survival time and delayed the development of hepatic congestion. However, injection of an ODC inhibitor into the mice given LPS did not produce hepatic congestion. 6. The induction of HDC in the liver by LPS, IL-1 or TNF was not suppressed by GalN and, at high doses, the response to LPS was enhanced. An inhibitor of HDC neither prevented the hepatic congestion nor enhanced the protective effect of putrescine.7. Although GalN in combination with IL-la induced a markedly higher HDC activity than was observed when it was combined with TNFa, and suppressed the induction of ODC, the former combination at the doses used did not produce hepatic congestion or death. However, the sensitization to TNFa by GalN was markedly potentiated by IL-la.8. These results suggest that suppression of the induction of ODC by GalN may be one cause of the sensitization to LPS, IL-1 or TNF, and that the induction of HDC, i.e. histamine formation, may not be involved in this sensitization.9. These results are consistent with the hypothesis that both IL-1 and TNF are involved in the sensitization to LPS.


The effect of aliphatic alcohols on the transient potassium current in hippocampal neurones. 1. The transient potassium current was recorded in single hippocampal CA1 neurones from the rat by use of the whole-cell patch clamp technique. The effects on this current of a homologous series of aliphatic alcohols, ranging from butanol to octanol, were investigated. 2. The predominant effect of octanol (and the other alcohols) was to cause an increase in the initial rate of decay of the transient potassium current together with a slight decrease in the rate of decay of later phases of the current, such that the current decay became markedly non-monotonic. The alcohols also caused a decrease in peak current amplitude which could not be accounted for solely by the change in current decay kinetics. 3. The effect of the alcohols was concentration-dependent and readily reversible. Increasing chain length increased the potency of each alcohol by about 3 fold for each methylene group added. Other than a difference in potency, there appeared to be little difference in the action of aliphatic alcohols of different chain length on the transient current. 4. The alcohols did not appreciably change the voltage-dependence of steady state inactivation or activation of the transient potassium current. 5. The rate of inactivation of the transient current in these cells was only weakly voltage-dependent. This weak voltage-dependence was not changed by the presence of aliphatic alcohols, neither was the effect of the alcohols themselves voltage-dependent. 6. The potencies of each of the aliphatic alcohols were well correlated with their respective membrane/buffer partition coefficients, a finding which implies a hydrophobic locus of action.


False consensus and out-group homogeneity: a methodological note on their relationship. Two different lines of research in social psychology ask subjects to generate estimates of the percentage of group members who they think would espouse some position or make some behavioural choice. Research on the false consensus effect has shown that such estimates are influenced by the subject's own choice. Research on out-group homogeneity has shown that such estimates are higher for group stereotypic choices than counterstereotypic ones and that this difference in turn is more pronounced for out-groups than in-groups. In this article we explore the relationship between these two effects, both of which rely on the same dependent measure. We show that out-group homogeneity will be estimated with bias unless the subject's own choice is included as a factor in the analysis, whenever false consensus is present and whenever the two target groups differ in the prevalence of their actual choices. We demonstrate this confounding with both hypothetical and actual data.


Modelling and suicide: a test of the Werther effect. The present study investigates whether news about suicides of prominent persons evokes an imitative effect. To this end, daily overall suicide frequencies of a German federal state, Baden-Württemberg, were examined for the years 1968 to 1980 and were related to prominent suicides that were publicized in major newspapers. Data were analysed quasi-experimentally and by means of a time series regression analysis. These methods yielded significant or marginally significant increases, respectively, for the week following the news. Alternative social psychological explanations were examined, and possible statistical artifacts were taken into account. The results are on the whole consistent with the assumption of an imitative effect.


Judgements about victims and attackers in depicted rapes: a review. This paper reviews the effects on subjects' judgements of a variety of factors that have been included in experimental depictions of rape. The focus is on attribution of responsibility or fault to the victim or attacker and related judgements, particularly regarding guilt and sanctions. Generally, females make more pro-victim judgements than do males, and people with non-traditional sex-role attitudes make more pro-victim judgements than do holders of more traditional views. Other factors covered are various victim characteristics, victim-attacker acquaintance, resistance, and victim attire and a range of behaviours prior to the attack. These are limits to generalization due to populations studied and methods used, and the observed effects of several factors are either minimal or inconsistent. However, some factors have reliable effects on judgements, which it is argued are explainable in terms of their link with traditional beliefs about women's rights and roles. Males have often been found to be more susceptible to these effects. In particular, it appears that if a female engages in any behaviour deemed to be 'incautious' that results in victimization then she may be perceived to be at fault, even though these behaviours would be 'legitimate' for males, and that prior romantic involvement with the attacker mitigates the perceived seriousness of, and may even be seen as supplying justification for, a sexual attack. The existence of these attitudes implies that rape may be tacitly condoned in many situations.


Blushing, embarrassability and self-consciousness. A blushing questionnaire and the Self-Consciousness scale (SCS) were completed by 86 respondents. A measure of the tendency to blush correlated significantly with the Social Anxiety subscale of the SCS, but not with the public and private subscales. Self-rated tendency to blush was significantly correlated with rated likelihood of blushing in those situations where the individual had some responsibility for an embarrassing incident, but not in situations where others had instigated the incident.


The red nucleus and mesencephalic tegmentum in a ranid amphibian: a cytoarchitectonic and HRP connectional study. Movement control in vertebrates is a complex function that is known to involve several parallel systems. In amphibians, which lack the isocortical structures shown in mammals to initiate and control voluntary movements, supraspinal motor control systems have received surprisingly little attention. Because amphibians lack a corticospinal equivalent, coordination and control of all movement strategies must take place in non-cortical, supraspinal integrating centers. The rubro-cerebello-rubrospinal circuit is likely to represent a major motor control system in such vertebrates. In this anatomical investigation four mesencephalic tegmentospinal projection nuclei are described in ranid amphibians (Rana catesbiana and Rana pipiens): reticular formation, accessory optic complex, interstitial nucleus of Cajal, and the red nucleus. The red nucleus, which shows no distinct somatotopic organization, can be distinguished because it is the only one of the four that is predominantly contralateral in its projections. Horseradish peroxidase injections into the tegmentum and the cerebellum demonstrated that the red nucleus also maintains reciprocal connections with the cerebellum via the deep cerebellar nucleus. These connections could not be localized to any distinct region in the deep cerebellar nuclear mass, suggesting that this represents a single cerebellar recipient nucleus. Thus, anuran amphibians are shown to possess the major pathways that comprise the rubro-cerebello-rubrospinal circuitry in mammals.


Ultrastructure and distribution of epidermal sensory receptors in the beak of the echidna, Tachyglossus aculeatus. Within the rostral one centimetre of the Echidna beak, three specialised receptors were found: a mucous sensory gland, a rod-like structure, and an innervated epidermal pit. The mucous sensory gland consists of a dermal mucous gland and a modified epidermal portion. Bulbous nerve terminals, similar to those reported for the Platypus, were found within the modified epidermal portion of the mucous gland. The rod-like structure contains four types of nerve terminals: Merkel cells, Paciniform corpuscles, and a central and a peripheral vesicle chain receptor. Apart from minor differences, the rod-like structure is similar to that previously reported for the Platypus. Preliminary results are presented for a third structure: an innervated epidermal pit. Topographical and ultrastructural analyses are used in the context of functional interpretation.


Central projections of the vagus nerve in Chelon labrosus Risso (Teleostei, O. Perciformes). The primary projections of the vagus nerve and its nuclei in a perciform teleost, Chelon labrosus, are described after application of hoseradish peroxidase (HRP) labeling and Nissl and silver staining methods. The vagus nerve has three peripheral roots, rostral, medial and caudal, which are formed from viscerosensory and visceromotor rootlets. In addition to viscerosensory and visceromotor rootlets, the caudal root has a cutaneous root and a 'descending' root. Dorsally in the caudal root, a fiber bundle enters the medulla from the retroocular and opercular skin region; this bundle joins the descending trigeminal root and courses with it rostrally and caudally. Fibers from another rootlet, which enters dorsolaterally, course caudally towards the spinal cord. This rootlet has not been described in other fishes. The vagal viscerosensory nucleus, where most of the viscerosensory fibers terminate, forms a column in which two types of neurons can be distinguished. The most caudal part of the nucleus is continuous with the commissural nucleus, into which vagal nerve projections also enter. No vagal projections were found in the area postrema. In the visceromotor column, two types of neurons are seen lateroventral to the IV ventricle.


The effects of background pattern and contrast on prey discrimination by the praying mantis Sphodromantis lineola (Burr.). Tethered, adult female Sphodromantis lineola (Burr.) were presented with two groups of two-dimensional stimuli (i.e., 2-D lures) against various backgrounds. Lure Group 1 comprised various black rectangles in three different size arrays: each size array included a 2, 6, or 12 mm square, respectively, several 'worm' lures of a constant width (l2, edge perpendicular to the direction of movement, 3-30 mm), but varying in length (l1, parallel to the direction of movement, 6-114 mm), and several 'antiworm' lures of a constant length but varying width. Group 1 lures were presented against patterned backgrounds of similar luminance: one natural pattern mimicking foliage and the other a random geometric pattern of rectangles. Group 2 lures comprised various configurations and combinations of black and white lures which were presented against white, black, and natural pattern backgrounds. The appetitive behaviors of approaching and striking at a lure were dependent measures indicating that a stimulus was categorized as prey. For Group 1 lures, overall response rates to lures of the same size were enhanced by the natural pattern background rather than the geometric pattern background. Against the natural pattern background, worm lures were stronger releasers of predatory behavior than antiworm lures of the same size. Lure configuration (especially for the smallest array) was masked by the geometric pattern background, although worm versus antiworm discrimination was apparent with the largest size array. For Group 2 lures, lure-to-background contrast, as well as configuration, effected prey recognition. For instance, lures with low lure-to-background contrast ratios were weaker releasers than those with high ratios, and lures that were darker (versus lighter) than the background were stronger releasers. In addition, particular stimulus properties interacted to effect lure strength. For instance, a weak or strong releaser became stronger or weaker, respectively, when a more or less, respectively, preferred releaser was super-imposed. The results also suggest that S. lineola attends preferentially to the leading edge of a moving stimulus. These findings are in agreement with predatory behavior of praying mantises in the wild.


Retinal projections in the house musk shrew, Suncus murinus, as determined by anterograde transport of WGA-HRP. Retinal projections in the house musk shrew (Suncus murinus) were determined by the anterograde transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). Unilateral injection of WGA-HRP into the vitreous body resulted in the terminal labeling of the optic projections in the suprachiasmatic nucleus (SCH), the ventral (CGLv) and dorsal (CGLd) lateral geniculate nuclei, the intergeniculate leaflet (IGL), the pretectum, the superficial layers of the superior colliculus (CS), and the dorsal terminal nucleus (DTN) of the accessory optic system (AOS). Labeling of the SCH was bilateral, with ipsilateral predominance, and covered the whole dorsoventral extent of the nucleus. Immunohistochemical studies revealed that VIP-like immunoreactive neurons and fibers were present in almost all parts of the SCH. No hypothalamic regions other than the SCH received the optic fibers. The ipsilateral projections to the CGLv, CGLd, and IGL were sparse, and a considerable number of uncrossed retinal fibers were found in the pretectal olivary nucleus. No retinal projections to the lateral posterior thalamic nucleus (LP) were found. Ipsilateral optic fibers projected sparsely to the medial part of the CS. The AOS consisted of a small DTN with a very few crossed retinal projections but no lateral and medial terminal nuclei. In addition, the AOS had no inferior fascicle.


Effects of serotonin and carbachol on glial and neuronal rubidium uptake in leech CNS. Effects of serotonin (5-HT) and carbachol on Rb uptake (used as a K marker) in leech neuron and glia were studied by electron probe microanalysis (EPMA). Hirudo medicinalis ganglia were perfused 60 s in 4 mM Rb substituted normal leech Ringer's with and without 5-HT (dosage range 5-500 microM) or carbachol (range 10-1000 microM), quench frozen cryosectioned, and subjected to EPMA to determine elemental mass fractions and cell water content. Both 5-HT and carbachol altered leech neuron and glial cell elemental distribution and water content. In glial cells, a dose-dependent increase in Rb uptake was observed following 5-HT (control: 26 +/- 2 microM; 5 microM: 47 +/- 4; 50 microM: 62 +/- 4; 500 microM: 82 +/- 11 mmol/kg dry wt. +/- S.E.M.) and carbachol (10 microM: 35 +/- 3; 100 microM: 52 +/- 3; 1000 microM: 68 +/- 3 mmol/kg dry wt. +/- S.E.M.). In neurons, 5-HT and carbachol had small effects. 5-HT decreased glial and neuronal cell water content. Carbachol decreased neuronal (but not glial) water content by approximately the same amount (mean decrease 9%) regardless of dose. Both 5-HT and carbachol affected glial cell K-accumulating properties, providing evidence that certain neurotransmitters may modulate invertebrate glial cells' K clearance function.


Histamine-immunoreactive nerve fibers in the rat pineal gland: evidence for a histaminergic central innervation. An immunohistochemical method that utilizes carbodiimide as a fixative and antisera directed against histamine was applied to investigate the location of histamine in the rat pineal complex. Numerous histamine-immunoreactive cell bodies were observed in different subdivisions of the tuberomammillary nucleus of the posterior hypothalamus, and a few cell bodies were present in the posterior and dorsal part of the periventricular hypothalamic nucleus. Histamine-immunoreactive fibers were observed to leave the posterior hypothalamus in various directions of which one dorsally projecting tract was followed in the periventricular area of the caudal diencephalon to the epithalamus. Several histamine-immunoreactive nerve fibers of this tract continued through the posterior commissure directly into the deep pineal gland. A few immunoreactive fibers were also observed in the habenular commissure. In midsagittal sections, histamine-immunoreactive nerve fibers were observed to enter the pineal stalk from the deep pineal gland. Most of histamine-immunoreactive fibers in the stalk continued towards the superficial pineal gland, but their number decreased in more distal locations of the stalk, indicating that some fibers terminate in the stalk as well. A few fibers were found to terminate in the most rostral part of the superficial pineal gland. The immunoreactive nerve fibers in the epithalamus and pineal complex were endowed with prominent varicosities. Taken together, these results indicate that histaminergic nerve fibers, originating from the posterior hypothalamus, project to the pineal complex of the rat. Histamine must therefore be considered a putative neurotransmitter contained in the central innervation of the pineal gland, but its function in pineal physiology has so far not been elucidated.


Phosphate analysis and dephosphorylation of modified tau associated with paired helical filaments. We performed phosphate analysis of tau proteins isolated from normal human brain, tau proteins associated with paired helical filaments (PHF-tau), and Alzheimer tau not associated with PHF. These tau fractions were of high purity. Normal and Alzheimer tau were purified by heat treatment, acid extraction and calmodulin-affinity chromatography with or without HPLC. Fractions containing primarily PHF-tau polypeptides of 60, 64 and 68 kDa and their degraded fragments were purified either on a sucrose density gradient as filaments (PHF) or by heat treatment and acid extraction as amorphous proteins (PHF-tau). PHF and PHF-tau were found to contain 6-8 mol phosphate/mol protein while normal and Alzheimer tau proteins contained 1.9 and 2.6 mol phosphate/mol protein, respectively. Upon 2-h incubation with alkaline phosphatase, PHF lost two of the phosphate groups without apparent changes in the stability and morphology of PHF. The released phosphate originated from the N-terminal half of PHF-tau as determined by immunoblotting with antibodies to epitopes blocked by phosphorylation. Tau-1 and E-2, and by a prominent shift in the electrophoretic mobility of some fragments of PHF-tau. The shift in mobility was not observed with the C-terminal fragments of 25-26 kDa, which retained the epitope to Tau 46. The results suggest that the phosphorylation sites not affected by phosphatase may be located in the 25-26 kDa C-terminal region of PHF-tau and may play a role in structural stability of PHF.


Role of tau in the polymerization of peptides from beta-amyloid precursor protein. The composition of paired helical filaments (PHFs), the intracellular amyloid fibrils that accumulate in the brains of Alzheimer patients, is not completely known. We investigated whether synthetic peptides from beta-amyloid precursor protein (APP) can form PHF-like fibrils. Two peptides formed fibrils morphologically similar to PHFs. The presence of tau protein, a known PHF component, greatly enhanced the numbers of fibrils formed from one peptide, from the C-terminus of APP, and became associated with the fibrils. A tau fragment corresponding to the tubulin-binding region was sufficient to induce fibril formation. Tau did not alter fibril formation by the other peptide, which was from the beta/A4 region of APP. These results raise the possibility that a C-terminal fragment of APP, along with tau, may be involved in PHF formation. Thus the proteolytic processing of APP may generate fragments that contribute to both amyloids and both histopathologic lesions of Alzheimer's disease.


Spontaneous alternation and inhibitory avoidance impairments with morphine injections into the medial septum. Attenuation by glucose administration. Peripheral glucose administration attenuates impairments produced by peripheral injections of the opioid agonist, morphine, on spontaneous alternation. Injections of opioid agonists directly into the medial septum also impair memory. The present experiments examined whether systemic and intraseptal glucose injections could attenuate deficits on spontaneous alternation and inhibitory avoidance in rats treated with intraseptal morphine. Morphine (3.95 nmol) injected into the medial septum significantly impaired performance on spontaneous alternation and inhibitory avoidance tasks. Both systemic (100 mg/kg, i.p.) and intraseptal (18.33 nmol) injections of glucose, administered concomitantly with intraseptal morphine, attenuated the morphine-induced impairments on these tasks in rats. These findings suggest that one brain region where glucose may act is the medial septum, possibly by releasing opioid inhibition of cholinergic activity.


The pyrimido-pyrimidine derivative RA-642 protects from brain injury in a combined model of permanent focal ischemia and global ischemia reperfusion. The effects of pyrimido-pyrimidine derivatives (dipyridamole, RA-642 and mopydamole) on lipid peroxidation (inhibition of the production of malondialdehyde, MDA) in different regions of the rat brain were studied. Ferrous sulfate and ascorbic acid (FeAs) were used to induce lipid peroxidation via the formation of hydroxyl anions. The antiperoxidative effect of RA-642 (in the microM range) was 10 times more potent than that of dipyridamole. Mopydamole did not exert any inhibitory effect on MDA production. In a model of ischemia reperfusion with bilateral occlusion of the common carotid arteries for 1 h and restoration of circulation for a period of 2 h, dipyridamole inhibited FeAs-induced MDA production but did not protect from postischemic brain tissue damage (measured by mitochondrial reduction of tetraphenyl tetrazolium). RA-642 inhibited FeAs-induced MDA production and showed 50-67% protection from tissue damage as compared with untreated animals, while mopydamole did not inhibit MDA production and showed 30-48% protection. No correlation was found between inhibition of lipid peroxidation and protection from brain tissue damage.


AF102B, a novel M1 agonist, enhanced spatial learning in C57BL/10 mice with a long duration of action. Orally administered AF102B, a selective muscarinic M1 cholinergic agonist, improved spatial learning in C57BL/10 mice in the Morris water maze. In four experiments in which all drug-treated animals received only one single administration of AF102B, improvement of acquisition depended on two factors: pretreatment time (tp) and dose. When a standard tp of 1 h was used, AF102B exhibited a U-shaped dose-response curve that is characteristic of many nootropic agents: learning was significantly improved by dose levels ranging from 0.1 to 1 mg/kg p.o. When the tp was extended out to as long as 8 days, two new effects emerged: (a) 1 mg/kg, the dose that had been the peak active dose at 1 h, exhibited a biphasic time course of action, being active at 1 h or at all tp intervals from 3 h to 5 days, but not at 1.5 h; (b) 0.03 mg/kg, a dose that had been inactive at a tp of 1 h, was active at all tp intervals from 3 h to 5 days, but not at shorter (1 and 2 h) or longer (6-8 days) tp intervals. In another experiment, animals received 0.03 mg/kg for 1-5 consecutive days: this dose level was active if the tp interval between the last dose and the learning session was 24-120 h, but not if it was only 1 h. Thus AF102B enhanced cognition in mice with a longer duration of action than reported for traditional muscarinic agonists.


Afferent innervation of the vestibular nuclei in the chinchilla. II. Description of the vestibular nerve and nuclei. The morphological characteristics of the vestibular nuclei of the chinchilla were studied in horizontally cut serial sections of the brain stem. Horseradish peroxidase labeling allowed unambiguous delineation of the vestibular nuclei and areas of innervation by the vestibular afferent fibers. The cytoarchitecture of the vestibular nuclei was documented with the aid of camera lucida drawings and quantitatively evaluated with computerized methodology. The cellular groups identified in other species were found in the chinchilla. The superior vestibular nucleus (SN) originated ventromedial to the mesencephalic tract and nuclei of the trigeminal nerve. This nucleus contained medium-sized cells with a central group of larger cells (20-34 microns in diameter). It received its maximum vestibular innervation caudally in the ventrolateral and dorsal aspects of the nucleus. Fibers projected to the SN in bundles with thick fibers surrounded by thin ones. The lateral vestibular nucleus (LN) originated 0.9-1.2 mm below the rostral aspect of the vestibular area. It was ventrocaudal to the SN and contained many large cells with diameters of 45-60 microns. The LN was innervated mainly in the ventrocaudal aspect by oblique and transverse fibers that formed a dense mesh. The medial vestibular nucleus (MN) originated 0.3-0.6 mm caudal to the beginning of the SN, adjacent to the floor of the IVth ventricle. It extended for 3-4 mm along the SN, LN and descending vestibular nucleus (DN). The MN contained the densest and most homogeneous cells, which had diameters of 10-20 microns. This nucleus received its greatest innervation at the level of the vestibular root. Thin fibers traveled to the MN through the SN and LN. The caudal pole of the nucleus did not receive fibers. The DN originated 1.8-2.5 mm caudal to the origination of the SN, between the caudal LN and the MN. Caudally it replaced the LN. Most of the cells of the DVN were medium-sized, with diameters of 10-20 microns. The main vestibular innervation of the DN was in the lateral aspect of the nucleus. Tertiary fibers projected in small, separate bundles of uniform-sized thick fibers. The interstitial nucleus originated 1.1-1.4 mm from the beginning of the SN. It occupied the center of the vestibular root, 0.8-0.9 mm medial to the root entry zone. It contained a few large cells (greater than 20 microns in diameter), many medium-sized cells, and some small cells.(ABSTRACT TRUNCATED AT 400 WORDS)


Effects of cholecystokinin on sympathetic activity to interscapular brown adipose tissue. The effects of injecting cholecystokinin (CCK) into the third ventricle or into selected hypothalamic sites on electrical firing rate of sympathetic nerves to interscapular brown fat (IBAT) has been investigated in anesthetized rats. The hypothesis for these experiments was that there was a reciprocal relationship between sympathetic activity and food intake. Since CCK reduces food intake we predicted that CCK would stimulate sympathetic activity to IBAT. Following the injection of CCK into the third ventricle there was an increase in firing rate of sympathetic nerves to IBAT. When the peptide was injected into either the ventromedial hypothalamic nucleus (VMH) or lateral hypothalamic area (LHA), there was likewise an increase in sympathetic firing rate. The injection of CCK into the paraventricular nucleus produced a small decrease in sympathetic firing rate. In contrast, no effect was seen following injection of CCK into the preoptic area or dorsomedial hypothalamic nucleus. Thus, the VMH or LHA appear to be the principal hypothalamic areas mediating the stimulation of sympathetic activity to IBAT which is observed following the third ventricular injection of CCK. These studies support the hypothesis of a reciprocal relationship between the effects of CCK on the thermogenic component of the sympathetic nervous system and food intake and identify the VMH and LHA as the primary sites for this effect.


Corticotropin-releasing factor induces a place aversion independent of its neuroendocrine role. The purpose of the present experiment was to test the hypothesis that corticotropin-releasing factor (CRF), a polypeptide of 41 amino acids, when administered either intracerebroventricularly (i.c.v.) or subcutaneously (s.c.), has aversive properties in the conditioned place-preference paradigm. Five doses of CRF (0, 0.005, 0.05, 0.5, 5 micrograms) were tested. i.c.v. CRF induced a specific dose-dependent reduction of the amount of time spent in the environment previously paired with the administration of CRF. Furthermore, this CRF-induced place aversion was prevented by pretreatment with alpha-helical-CRF(9-41), a specific CRF antagonist, administered i.c.v. In order to test whether the aversive effects induced by i.c.v. CRF could result from the stimulation of the HPA axis accompanying i.c.v. CRF injection, the reinforcing properties of s.c. CRF were studied using the same dose range. Only the higher s.c. dose was effective in producing a place aversion suggesting that the aversive effects of CRF could not be due solely to the stimulation of the pituitary-adrenocortical system, measured by plasmatic levels of adrenocorticotropic hormone (ACTH) and corticosterone, because the lower doses consistently activate the pituitary-adrenocortical system without producing any behavioral changes. Altogether, these data indicate that the non-neurosecretory CRF neurons may mediate the aversive state occurring during stress.


Effects of intracisternal vs. intrahypothalamic 5,7-DHT on feeding elicited by hypothalamic infusion of NE. A variety of evidence has led to suggestions that brain serotonin (5-HT) and norepinephrine (NE) interact within the medial hypothalamus to control food intake. To test the possibility that chronic decrements in 5-HT might enhance NE-induced feeding, adult male rats were prepared with permanently indwelling cannulae aimed at the paraventricular nucleus (PVN), then received either intracisternal (IC) or PVN injections of the 5-HT neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT) vs. its vehicle, 1% ascorbic acid. Over a 4-week period, IC-5,7-DHT rats showed no signs of enhanced daily feeding or drinking. However, in 40-min intake tests, feeding but not drinking was enhanced by injecting 20 nmol NE into the PVN commencing 2 weeks after neurotoxin treatment. Terminal monoamine assays confirmed that IC-5,7-DHT produced large (80-90%) depletions of brain regional 5-HT. A functional index of 5-HT terminal damage was also implied by the impaired short-term feeding responses IC-5,7-DHT rats showed to the systemic administration of the 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) when tested between 3 and 4 weeks after IC treatment. Over a comparable 4-week period, PVN-5,7-DHT rats also showed no tendencies to overeat or overdrink on a daily basis. However, in contrast to IC-5,7-DHT rats, they also showed no differences in their feeding or drinking responses to NE injections into the PVN. This was so despite reliable depletions of 5-HT in the hypothalamus (-28%) and hippocampus (-71%). These results support earlier work showing that neither widespread nor localized hypothalamic damage to brain 5-HT neurons produce chronic overeating. However, the data suggest that phasic enhancements of PVN NE activity may trigger enhanced feeding when there is widespread damage to brain 5-HT neurons, although the PVN does not appear to be the brain site mediating this effect.


The spinal cord processing of input from the superior sagittal sinus: pathway and modulation by ergot alkaloids. The effects of ergot alkaloids on field potentials and unit responses produced in the upper cervical spinal cord by stimulation of the superior sagittal sinus (SSS) were examined in 57 anesthetized cats. Electrical stimulation of the SSS produced field potentials and single-unit responses at latencies of 5-20 ms. Field potentials were abolished by section of the first division of the trigeminal nerve but were unaffected or increased by section of the upper cervical nerves. Field potentials were reduced or abolished by intravenous injection of ergotamine or dihydroergotamine (DHE). The evoked response of 41 units (34.4%) were suppressed by either i.v. or iontophoretic administration of ergotamine, DHE or ergometrine. The results suggest that ergot alkaloids exert an effect at a spinal cord relay centre which receives trigeminally mediated input from cranial blood vessels.


Serotonin receptor subtype antagonists in the medial ventral medulla inhibit mesencephalic opiate analgesia. Supraspinal opioid analgesia is mediated in part by connections between the midbrain periaqueductal gray (PAG) and the ventral-medial medulla, including the nucleus raphe magnus (NRM) and nucleus reticularis gigantocellularis (NRGC). A serotonergic synapse appears to participate in this pathway since methysergide microinjected into the NRM-NRGC significantly reduced morphine analgesia elicited from the PAG. The present study evaluated the role of specific serotonin receptor subtypes by pretreating rats with microinjections of either the 5HT2 antagonist, ritanserin or the 5HT3 antagonist, ICS205930, into the NRM-NRGC and examining their effects upon morphine (2.5 micrograms) analgesia elicited from the PAG. Mesencephalic morphine analgesia was significantly reduced following pretreatment with both ritanserin (0.25-2.5 micrograms) on the tail-flick (81%) and jump (65%) tests and ICS205930 (0.25-5 micrograms) on the tail-flick (91%) and jump (63%) tests. Neither ritanserin nor ICS205930 altered basal nociceptive thresholds. Medullary placements ventral or lateral to the NRM/NRGC failed to support these antagonistic effects. These data indicate that ventro-medial medullary 5HT2 and 5HT3 serotonergic receptors modulate the transmission of opioid pain-inhibitory signals from the PAG.


Sarcoplasmic calcium-binding protein-immunoreactive material in the central nervous system of the snail, Helix pomatia. In Helix pomatia a 10 kDa sarcoplasmic calcium binding protein I (SCP I)-immunoreactive material was localized immunologically in neurons of the central nervous system, including the electrically silent serotonergic metacerebral giant neuron. Antisera against sarcoplasmic calcium binding protein II (SCP II) stained a 20 kDa protein in individual muscle cells of the epineurium. SCP- and parvalbumin (PV)-immunoreactive material were not co-localized.


Comparison of stimulated tissue factor expression by brain microvascular endothelial cells from normotensive (WKY) and hypertensive (SHR) rats. The amounts of tissue factor (TF) expressed by brain microvascular endothelial cells (BMECs) from normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were compared after stimulating the cells with different doses of lipopolysaccharide (LPS), thrombin, phorbol myristic acid (PMA), Ca(2+)-ionophore (A23187), or tumor necrosis factor (TNF) and interleukin-1 (IL-1). Treatment of cultured BMECs from WKY and SHR with all of these factors dose-dependently increased their total amount of TF; no substantive differences in the levels of enhanced TF expression were observed between WKY and SHR BMECs. We conclude that stimulated endothelium from rats with hypertension, a major stroke risk factor, is not hyperresponsive with respect to TF expression when compared to normotensive controls.


Visual and infrared input to the same dendrite in the tectum opticum of the python, Python regius: electron-microscopic evidence. In snakes with infrared receptors, the optic tectum receives input from both the visual and the infrared senses. We investigated the infrared and optic fiber terminations in the tectum with a combination of horseradish peroxidase and degeneration labeling. In addition to synapses by visual and infrared fibers onto individual neurons, we were able to observe for the first time visual and infrared synapses on one and the same dendrite.


The CRF neurosecretory vesicle: vasopressin-dependent changes in vesicle size after adrenalectomy. Neurosecretory vesicles of paraventricular corticotropin releasing factor (CRF) neurons increase in size after adrenalectomy (ADX) in parallel with an augmentation of their content in vasopressin (VP) immunoreactive sites. We have investigated in the Brattleboro rat model whether changes in vesicle size are related to elevated intravesicular concentrations of VP. Using quantitative immunoelectron microscopy, VP and CRF immunoreactive sites were assessed in the dense core vesicle compartment of CRF axon terminals in the median eminence. In heterozygous (control) rats, CRF was co-packaged with VP, and ADX induced a 3-fold increase in VP labeling intensity and produced a significant increase in the vesicle diameter. In homozygous rats lacking VP, only CRF immunoreactivity was detectable, and ADX was not accompanied by an increase in vesicle size. These observations suggest that the presence of VP is necessary for the ADX induced increase in vesicle size and that this increase might be needed to accommodate the excess of VP in the vesicle space.


An atlas of the rat subpostremal nucleus tractus solitarius. The nucleus tractus solitarius (NTS) in the dorsal medulla is the principal visceral sensory relay nucleus in the brain. In the rat, numerous lines of evidence indicate that the caudal NTS at the level of the area postrema serves as a major integrating site for coordinating cardiorespiratory reflexes and viscerobehavioral responses. This region of the caudal NTS not only exhibits high densities of binding sites for an impressive array of transmitters and modulators but microinjections of many of these same neuroactive substances into the rat subpostremal NTS elicit pronounced cardiorespiratory and visceral response patterns. This report provides an abbreviated atlas of the rat subpostremal NTS consisting of a series of transverse, sagittal, and horizontal plates. Photomicrographs, together with their corresponding schematic drawings, are provided for the serial sections generated from each reference plane.


Electrophysiological study of neurotropin-induced responses in guinea pig hypothalamic neurons. To investigate the direct actions of neurotropin (NSP, a nonproteinaceous extract from inflamed skin of rabbits which is in therapeutic use), intracellular recordings were made from neurons of the ventromedial hypothalamic nucleus (VMH) and lateral hypothalamic area (LHA) in slices of guinea pig brain. In the VMH, NSP, applied by perfusion (0.1-3.0 NU/ml), caused dose-dependent depolarization in 29 of 48 neurons (60%) tested. No change in membrane resistance was observed during the depolarization, which hypothesized that the NSP-induced depolarization might be mediated through the inactivation of the Na-K pump. The NSP-induced depolarization persisted even after the elimination of synaptic activity by perfusion with Ca(2+)-free and high Mg2+ Ringer solution. NSP hyperpolarized the cell membrane of three neurons (6%) while two neurons (4%) showed biphasic responses; transient depolarization followed by long-lasting hyperpolarization. Membrane potential of the remaining 14 neurons was not changed by application of NSP. Of 14 LHA neurons tested for NSP effects, eight (57%) were depolarized, three (21%) were hyperpolarized, and one showed a biphasic response. The present results suggest that NSP significantly modulates hypothalamic neuron activity, and the central modulation of autonomic functions by NSP might be mediated through hypothalamic neurons.


Responses of trigeminal subnucleus interpolaris neurons to afferent inputs from deep oral structures. Responses of trigeminal subnucleus interpolaris neurons to natural and electrical stimulation of the temporomandibular joint (TMJ) and the masseter muscle (Mm) were studied in the anesthetized rat. Interpolaris neurons could be placed in one of three classes determined by their responses to noxious and innocuous stimuli: Class I, excited by only innocuous stimuli; Class II, excited by only noxious stimuli; Class III, excited by both. In each class, the conduction velocities of the primary afferents were roughly equivalent to those of small-diameter fibers. Approximately 70% of the interpolaris neurons tested received nociceptive inputs from the TMJ and/or the Mm. Most of these neurons had extensive convergence of afferent inputs, including the TMJ, the Mm, and/or the facial skin. The results suggest involvement of interpolaris neurons in the characteristics of deep pain, such as its spread and referral.


Distribution of calbindin D-28K and parvalbumin immunoreactivities in the nucleus olfactorius anterior of the rat. The distributions of calbindin D-28K (CaBP) and parvalbumin (PV) in the rat nucleus olfactorius anterior (NOA) were described using monoclonal antibodies and the avidin-biotin-peroxidase method. The NOA showed a high immunoreactivity for CaBP, with a rostrocaudal increase in the positive neurons and fibres. Pars externa (NOAe) was the only subdivision which showed a low CaBP immunostaining. PV-positive elements were less abundant than those CaBP immunostained. The main difference in the distributions for both proteins was observed in the pars medialis which was practically PV negative. PV- and CaBP-stained neurons showed similar morphologies in the subdivisions where they were present. In NOAe, we observed a characteristic PV- and CaBP-positive neuronal type, with an oriented dendritic pattern. Transition areas were clearly observable in both CaBP- and PV-labelled sections.


Sialyl cholesterol enhances the development of grafted neurons and motor recovery. Trophic actions of alpha-sialyl cholesterol (SC) and its sialidase-tolerant derivative, alpha-(3 beta-hydroxysialyl) cholesterol (SCt), were carried out on the development of midbrain neurons both in vitro and in vivo transplantation studies. Low to moderate concentrations of SC (0.01 to 0.05 micrograms/ml) facilitated neurite extension but had no effects on cell survival of primary cultured midbrain neurons. However, high concentration of SC (0.1 micrograms/ml) disturbed both neurite genesis and cell survival. SCt had a similar effect on midbrain neurons. At higher concentrations, SC and SCt induced concentration-dependent morphological changes in astrocytes from flat to fibrous. The effect on astrocytes was stronger in SCt than SC. At highest concentration tested (20 micrograms/ml), the proliferation of astrocytes was completely blocked, cells became detached and finally died. This effect of SC and SCt was partially blocked by simultaneous application of aFGF. Following dopaminergic cell grafting in vivo, SC and SCt had biphasic effects: a low dose (0.2 mg/kg, SC) enhanced motor recovery at 4 and 6 weeks after transplantation, while the highest dose (20 mg/kg, SC) disturbed motor recovery at all periods tested. These effects on motor recovery were paralleled by an effect on neurite genesis as studied by tyrosine hydroxylase immunostaining. Thus, at low concentrations, SC and SCt are neurotrophic agents that stimulate the development and differentiation of dopaminergic neurons.


The role of interleukin-1 and tumor necrosis factor alpha in the neurochemical and neuroendocrine responses to endotoxin. Both interleukin-1 (IL-1) and endotoxin (lipopolysaccharide, LPS) are potent activators of the hypothalamo-pituitary-adrenal (HPA) axis, and they also increase cerebral norepinephrine metabolism and tryptophan. Injections of cause macrophages to synthesize and release various cytokines, including IL-1 and tumor necrosis factor alpha (TNF alpha). The hypothesis that macrophage production of IL-1 mediates the HPA-activating effect of LPS was tested in mice using the IL-1-receptor antagonist protein (IRAP). Administration of IRAP largely prevented the effects of IL-1 alpha or IL-1 beta on the elevation of plasma corticosterone and the concomitant increase in hypothalamic norepinephrine metabolism, but failed to alter the responses to LPS. IRAP did not prevent the increases in brain tryptophan that occurred after treatment with IL-1 or LPS. Recombinant human TNF alpha, TNF beta, IL-6, and interferon-alpha injected intraperitoneally failed to activate the HPA axis, but mouse TNF alpha was effective by this route, and human TNF alpha, TNF beta, and IL-6 were effective intravenously. None of these cytokines was as potent as IL-1. Pretreatment with an antibody specific for mouse TNF alpha, either alone or in combination with IRAP, also failed to prevent the elevation of plasma corticosterone by LPS. Thus, either IL-1 and TNF alpha are not involved in the HPA and noradrenergic responses to LPS, or there are alternative (redundant) pathways by which LPS can activate the HPA axis.


Light microscopic localization of angiotensin II binding sites in canine medulla using high resolution autoradiography. Angiotensin II (Ang II) produces dose-related, site-specific cardiovascular effects in the canine and rat dorsal medulla. Our previous studies suggested that Ang II binding sites are associated with presynaptic vagal afferent fibers in the nucleus tractus solitarii (nTS) and vagal efferent neurons in the dorsal motor nucleus of the vagus (dmnX). High resolution autoradiography now establishes the relationship of putative Ang II receptors to the cytoarchitecture of these nuclei. Sections of the canine medulla oblongata were processed for film or emulsion autoradiography with 0.3-1 nM 125I-Ang II. Quantitative densitometry of films before and after processing sections for emulsion coating confirmed no selective alteration in labeling. In emulsion coated sections, dense labeling was seen over the majority of the large perikarya and surrounding neuropil in the ventral dmnX. Bands of label overlaid vagal efferent fibers coursing ventrolaterally to exit the medulla. In the nTS, Ang II binding was restricted to regions with heavy vagal afferent innervation. In the dorsal nTS, label was distributed over both cell bodies and neuropil, with highest density capping the solitary tract. In the medial nTS, label was concentrated over perikarya, with scattered grains over the intervening neuropil. The discrete subnuclear association of Ang II binding sites in the dorsal medulla with vagal cells and fibers documents that Ang II receptors are present on both afferent vagal fibers and intrinsic medullary neurons, and reveals an anatomical substrate for the autonomic effects of Ang II in this region.


Increases in the locomotor activity of rats after intracerebral administration of cathinone. There is a widespread practice among people living in Eastern Africa and Southern Arabia of chewing the leaves of the Khat shrub so as to produce pharmacological effects that are practically indistinguishable from those produced by amphetamine (AMPH). Cathinone (CATH) has been identified as the psychostimulant constituent of this plant and, although the locomotor elevating effects of centrally administered AMPH and cocaine (COC) in rats are well known, there is a paucity of data regarding CATH. Three experiments were, therefore, conducted to measure locomotor activity following central administration of CATH in rats. The first experiment determined the dose-dependent effects of CATH on activity following intracerebroventricular (ICV) administration. As psychostimulant effects are believed, at least in part, to be mediated by dopaminergic systems, in Experiment 2 CATH was injected into the dopamine nerve terminals of the nucleus accumbens. Experiment 3 examined the effects of CATH injection into the dopamine cell body region of the substantia nigra, and activity was measured. Results of the ICV injection of CATH revealed a dose-dependent increase of activity. The highest dose tested (64 micrograms) yielded a 117% increase in activity when compared to baseline, whereas a 20 micrograms bilateral nucleus accumbens (NA) injection of CATH increased activity fivefold. These findings evidence the hypothesis that the effects of CATH are dopaminergically mediated. Substantia nigra (SN) injections of CATH were without effect.


Intake of sweet water attenuates restraint-stress-induced potentiation of morphine analgesia in rats. The analgesia induced in rats by morphine is potentiated by restraint-stress exposure and is reduced in rats that have been consuming a sweet solution. The purpose of the present study was to determine whether the potentiation of morphine-induced analgesia following restraint immobilization would be attenuated in rats consuming a sweet solution. Groups of rats were maintained on unsweetened water or allowed 2 h of daily access to a solution of saccharin and glucose (SG). Half of the rats in each of these groups were subjected to 1 h of restraint stress (groups RS and RS+SG) and the other half in each group were not stressed (groups NS and NS+SG). Rats then underwent 1 h of RS treatment or were nonstressed (NS). The next day all rats were injected subcutaneously with morphine (0.0, 4.0, 8.0, or 16 mg/kg) and analgesia was assessed using the tail flick assay. ED50S (mg/kg) were calculated for each treatment group; NS = 5.8, RS = 1.6, NS+SG = 6.4, and RS+SG = 4.4. Our results demonstrate that RS potentiated morphine-induced analgesia in rats given access to SG as well as non-SG exposed rats that displayed ED50S 1.5 and 3.9 times lower than their respective controls. RS-treated rats that consumed SG solution had significantly lower tail flick latencies than did non-SG exposed rats. Additionally, tail flick latencies of rats in the nonstressed and NS+SG groups did not significantly differ. We conclude that the brain mechanism(s) responsible for RS-induced potentiation of morphine antinociception are attenuated by intake of a sweet solution.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of d-fenfluramine on neuropeptide Y concentration and release in the paraventricular nucleus of food-deprived rats. Recent evidence indicates that Neuropeptide Y (NPY) is an important signal in the hypothalamic neural circuitry that stimulates feeding in the rat. Administration of d-fenfluramine (FEN) has been shown to rapidly inhibit feeding in the rat. Because food deprivation increases the levels and release of NPY in the paraventricular nucleus (PVN) of the hypothalamus, the aim of this study was to investigate whether the rapid anorectic effects of FEN in food-deprived (FD) rats are associated with alterations in the hypothalamic NPYergic system. In the first experiment, the effect of FEN (10 mg/kg) on NPY concentrations in nine microdissected hypothalamic sites was assessed by radioimmunoassay (RIA) in rats either food deprived for 3 days or fed ad lib during the experimental period. In response to food deprivation, NPY concentrations increased significantly in the PVN and arcuate nucleus, but NPY levels remained unchanged in the remaining seven hypothalamic sites. In control rats maintained on ad lib food supply, FEN injection produced little effect on NPY concentration in hypothalamic sites. However, FEN suppressed NPY levels selectively in the PVN of FD rats, so that NPY concentrations measured in the nucleus were within the range found in satiated control rats. In the second experiment, the effect of FEN on NPY release in the PVN was examined in FD rats by the push-pull cannula (PPC) technique. NPY levels in the PPC perfusate were unchanged in FD rats during the period 30-120 min after saline or FEN injection. Also, the mean rate of NPY release was similar in vehicle- and FEN-treated FD rats.(ABSTRACT TRUNCATED AT 250 WORDS)


Excitation of inspiratory neurons by preinspiratory neurons in rat medulla in vitro. In brain stem-spinal cord preparations isolated from newborn rats, we examined synaptic connections to inspiratory neurons from preinspiratory (Pre-I) neurons, by spike-triggered averaging. Potentials were simultaneously recorded intracellularly from inspiratory neurons, and extracellularly from Pre-I neurons in the ipsilateral ventrolateral medulla. The Pre-I neuron pulses were used to trigger computer averaging of potential changes. A total of 16 pairs were analyzed, and EPSP-like depolarizing potentials locked to the triggering Pre-I spikes were obtained from three pairs. Latency from the Pre-I spikes was 3.4-4.5 ms, and the amplitude was 0.07-0.4 mV. These connections were concluded to be monosynaptic, because the antidromic latency was 3.6 +/- 1.5 ms. The present results suggest the presence of excitatory synaptic connections from Pre-I neurons to inspiratory neurons in the ventrolateral medulla. These excitatory synaptic connections are probably important in the initiation of inspiratory burst activity.


Intracerebral infusion of DOPAC decreases striatal dopamine. The purpose of this study was to determine whether elevated levels of 3,4-dihydroxyphenylacetic acid (DOPAC), the major metabolite of dopamine (DA) in the brain, could decrease the DA content in the striatum. Levels of DA were determined by high pressure liquid chromatography with electrochemical detection (HPLC-EC) in the striatum of male rats 24 h following a single intracerebral administration of DOPAC into the right striatum. DOPAC at 16.8 micrograms reduced the DA content of the infused side by 17%, p = 0.01. In contrast, infusion of 1.68 micrograms of DOPAC or the vehicle had no effect on striatal DA levels. Coapplication of the antioxidant, ascorbic acid, at 0.2 mg/ml with 16.8 micrograms of DOPAC prevented the decrease in DA content. Furthermore, infusion of 18.2 micrograms of homovanillic acid (HVA), the product of DOPAC methylation, had no effect on striatal DA. These results indicate that DOPAC may undergo autoxidation in vivo to produce neurotoxic species which may result in reduction of striatal DA. Formation of such an autoxidation product(s) of endogenous DOPAC was verified in the extracellular fluid of striatal slices in vitro.


Chronic intracerebral infusions of vasopressin and vasopressin antagonist modulate behavioral effects of interleukin-1 in rat. To assess the role of sex dependent brain vasopressinergic transmission in the modulation of the neural effects of interleukin-1, castrated male rats that are deficient in vasopressin were implanted intracerebroventricularly with an Accurel collodion mini device containing 10 micrograms AVP whereas intact male rats were implanted with a similar device containing 50 micrograms of dPTyr(Me)AVP, a specific antagonist of the vasopressor-like receptors of vasopressin. Control rats in each sex group were implanted with an Accurel device containing distilled water. Acute intracerebroventricular injection of 1.25-2.50 ng recombinant human interleukin-1 beta decreased in a dose and time-dependent manner social investigation of a juvenile conspecific. This effect was more intense in intact rats chronically infused with dPTyr(Me)AVP and less intense in castrates infused with AVP. These results confirm the modulatory role of sex-dependent vasopressinergic neurotransmission on the neural effects of interleukin-1.


Behavioral profile of the 5HT1A receptor antagonist (S)-UH-301 in rodents and monkeys. The effects of the new 5HT1A receptor antagonist (S)-UH-301 were investigated in several neurological and behavioral tests in rodents and monkeys. By itself, (S)-UH-301 was found to decrease palatable food consumption in rats, to exhibit anticonvulsant activity in mice, and anxiolytic-like properties in two rodent models of anxiety (light-dark test and elevated plus-maze test). (S)-UH-301 antagonized various symptoms and behaviors induced by the selective 5HT1A receptor agonist 8-OH-DPAT, such as lower lip retraction and flat body posture in rats, hyperphagia for palatable food in rats, and displacement activities (considered as indices of anxiety) in squirrel monkeys. These results further characterize (S)-UH-301 as an in vivo active 5HT1A receptor antagonist and suggest that this antagonistic activity might confer the compound with anxiolytic-like properties.


Feeding disturbances and EEG activity changes after amygdaloid kainate lesions in the rat. Kainic acid (KA), in various concentrations, was applied iontophoretically into the central nucleus of the amygdala. Microlesions with this cell specific neurotoxin caused body weight loss, hypo- or aphagia and hypo- or adipsia in a dose-dependent manner. EEG-examinations proved that even low doses of KA produced seizure activity; however, these epileptiform symptoms disappeared within the first 48 h after the operations. Thus, the lasting feeding disturbances produced by iontophoretic KA applications to the central nucleus of the amygdala (i.e., even these fine microlesions) were not related causally to the pathological EEG activity changes. Our findings, along with previous data, indicated that the body weight loss and feeding deficits were due to the KA-induced impairment of complex regulatory mechanisms.


Adherence of botulinum and tetanus neurotoxins to synaptosomal proteins. The ability of 125I-labeled botulinum type A and tetanus neurotoxins to adhere to blots of synaptosomal proteins separated by SDS-polyacrylamide gel electrophoresis was studied. Both neurotoxins appeared to adhere preferentially to an approximately 80 kDa and to a lesser extent to an approximately 116 kDa protein(s). Adherence of the neurotoxins to these proteins was enhanced by preincubation of the neurotoxins with GT 1b. The approximately 100 kDa heavy chain segment of BTxA adhered to the same proteins. The carboxy terminal half of the heavy chain adhered primarily to the approximately 80 kDa protein(s) while the amino terminal portion bound most intensely to the approximately 116 kDa protein(s). The ability of the approximately 80 and approximately 116 kDa proteins to stain positively with the periodic acid-Schiff reagent and to bind 125I-labeled wheat germ lectin suggests that they are glycosylated. Both neurotoxins appear to adhere to the same approximately 80 and approximately 116 kDa proteins because tetanus neurotoxin preincubated with GT 1b was able to reduce binding of radiolabeled botulinum type A neurotoxin to both proteins. Neither neurotoxin adhered to blots of proteins from liver, spleen, or kidney, suggesting that the proteins adhered to are neural components.


Corticofugal input to taste-responsive units in the parabrachial pons. Taste responses in units in the parabrachial nucleus of the pons (PbN) that receive direct projections from the gustatory neocortex (GN) were examined in the rat. Electrical stimulation was applied to the GN with bipolar stimulating electrodes. Time-locked responses to GN stimulation were observed in 19 of 62 (31%) taste-responsive units identified in the PbN. Of these, 17 units produced excitatory responses following GN stimulation and 2 units showed evidence of inhibition. No evidence of antidromic activation of PbN units was apparent. These results are consistent with descriptions of the anatomical projections from the GN to the PbN and demonstrate that some portion of taste-responsive neural elements within the PbN receive direct cortical input. PbN units that followed GN stimulation could not be distinguished from those that did not follow either by their spontaneous rates or their response profiles. These results suggest that axons from the GN do not select targets within the PbN based on the particular response properties.


GABAergic innervation of serotonergic neurons in the dorsal raphe nucleus of the rat studied by electron microscopy double immunostaining. A double immunocytochemical method combining the preembedding PAP technique and the postembedding immunogold technique was used to examine interactions between GABAergic and serotonergic neurons in the same tissue sections of the dorsal raphe nucleus of the rat. A large number of immunogold stained GABAergic axon terminals were found to be presynaptic to strongly PAP immunostained serotonergic perikarya and dendrites. The types of synapses were mostly symmetrical although a few asymmetrical ones were also found. No axo-axonic synapse between the GABAergic axon terminals and the serotonergic neuronal profiles was found. These results suggest that GABAergic neurons could modulate serotonergic neurons in the dorsal raphe nucleus through synaptic relations.


Quantitative scintigraphy of the sacroiliac joints. The effects of age and laterality on sacroiliac (SI) to sacral indices and ratios were assessed in 62 patients. For the 14 controls, the left mean SI to sacral index was significantly higher than the right one. There was no correlation between age and SI to sacral ratio (= average of right and left index). The mean ratio in 36 patients with sacroiliitis and 12 patients with low back pain was not significantly different from that of the controls, with a clear overlap of indices between controls and sacroiliitis patients.


Hepatic arterial color Doppler signals in Caroli's disease. Three siblings with congenital dilatation of the intrahepatic bile ducts (Caroli's disease) are presented. Bile duct pathology was associated with congenital hepatic fibrosis and polycystic renal disease in all three patients. On color Doppler imaging (CD imaging), multiple small color Doppler signals were observed in the vascular radicles within the dilated bile ducts or in the center of the lumen apart from the vascular radicles, as well as in other well-known sonographic findings such as bile duct dilatations and bilary calculi. Doppler frequency spectral analysis confirmed all these color signals as arterial in origin in all patients, revealing pulsatile wave patterns. In spite of the fact that portal venous radicles have been well described on conventional sonograms or computed tomography (CT), continuous wave patterns of venous flow on spectral analysis were not detected in all patients. Identification of such less emphasized arterial flow may add another clue in the diagnosis and pathogenesis of this rare disease entity. In conclusion, color Doppler signals of arterial wave pattern within the dilated bile ducts are another helpful diagnostic criteria in previously reported sonographic findings, and these color signals are easily depicted on sonograms with color mapping.


Spontaneous intraperitoneal rupture of bladder with spontaneous healing. A case of spontaneous intraperitoneal bladder rupture that was spontaneously healed in a one-year-old girl is reported. The subsequent drainage of the contrast medium in the peritoneal cavity via the urethral catheter after retrograde cystography implies that such a rupture may be successfully treated by a urethral bladder drainage and antibiotics.


Radiology of the pleural fissures.

Radiology of the pleural fissures. The pleural fissures, formed by a double layer of visceral pleura, represent extensions of the pleural space between lobes of the lungs. The fissures are frequently an anatomic barrier to the spread of inflammatory or neoplastic disease. Identification of the fissures is important for the accurate localization of lung parenchymal or pleural pathology. The plain radiographic and computed tomographic (CT) imaging of normal and variant fissural anatomy, as well as of some abnormalities that may affect the fissures will be reviewed and illustrated.


MRI spectrum of medulloblastoma.

MRI spectrum of medulloblastoma. Medulloblastomas have been characterized as solid, homogeneously enhancing, midline masses of the posterior fossa. To evaluate atypical MRI characteristics, we retrospectively reviewed 13 histologically proven medulloblastomas. MRI examinations were correlated with pathologic specimens and operative reports. Atypical features included cyst formation (77%), irregular enhancement (19%), extension through fourth ventricle foramina (15%), and presentation as a cerebellopontine angle mass (8%). We conclude that "atypical" characteristics are common. In the child or young adult, medulloblastomas must be included in the differential diagnosis of any posterior fissa mass.


Sonography and computed tomography of a gossypiboma and in vitro studies of sponges by ultrasound. Case report. A case of retained surgical sponge was imaged by ultrasound and computed tomography (CT). Sonography revealed a hypoechoic mass with areas of high echoes and acoustic shadowing. An experiment revealed that the high echoes were attributed partly to the presence of numerous interfaces of sponges. The sonographic detection of a mass with high echoes casting acoustic shadows should alert radiologists to the possibility of retained surgical sponges even if there is no gas or calcification on CT scans.


Magnetic resonance imaging of retained surgical sponges. Case report. The magnetic resonance imaging (MRI) features of sponges retained postsurgically in three patients are described. MRI depicted these as well-defined round masses, which were of low signal intensity on T1-weighted images and very high signal intensity on T2-weighted images. We scrutinized these masses on T2-weighted images. MRI revealed the low-signal-intensity structures to have wavy, striped, and/or spotted appearances, which raised the suspicion that they might be retained surgical sponges within mass lesions.


Inactivation of cytochrome P450 and inhibition of ferrochelatase by analogues of 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine with 4-nonyl and 4-dodecyl substituents. Cytochrome P450- and heme-destructive effects of the 4-nonyl and 4-dodecyl analogues of 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine (DDC) were determined using hepatic microsomal preparations obtained from untreated, beta-naphthoflavone-treated, and phenobarbital-treated chick embryos. The 4-nonyl analogue of DDC was less efficacious than 4-ethyl DDC and 4-hexyl DDC, but more efficacious than 4-dodecyl DDC with respect to cytochrome P450-destructive activity. In all hepatic microsomal preparations, cytochrome P450 destruction by 4-nonyl DDC was accompanied by loss of microsomal heme. In contrast, 4-dodecyl DDC caused loss of heme only in hepatic microsomal preparations obtained from phenobarbital-treated chick embryos. The ability of 4-nonyl DDC and 4-dodecyl DDC to lower ferrochelatase activity was compared with that of 4-ethyl DDC and 4-hexyl DDC in cultured chick embryo hepatocytes. As the length of the 4-alkyl group was increased, the ferrochelatase-lowering efficacy and potency of the DDC analogue decreased. The 4-dodecyl DDC analogue was unable to lower ferrochelatase activity, which accorded with the finding that the administration of 4-dodecyl DDC to phenobarbital-treated rats did not lead to the accumulation of an N-alkylprotoporphyrin. The ability of 4-nonyl DDC to lower ferrochelatase activity was attributed to the formation of N-nonylprotoporphyrin IX following the administration of 4-nonyl DDC to phenobarbital-treated rats.


MRI of dural carotid-cavernous fistulas. Comparisons with postcontrast CT. Ten patients with dural carotid-cavernous fistulas (CCFs) who presented with ophthalmic manifestations were studied using postcontrast computed tomography (CT), magnetic resonance imaging (MRI), and selective cerebral arteriography. The lesions of two patients were bilateral. An enlarged cavernous sinus (CS) was diagnosed in 6 of the 12 involved sides using postcontrast CT. An abnormal flow void in the CS was detectable in 11 of the 12 using MRI. A dilated superior ophthalmic vein (SOV) was demonstrated in all of the involved sides by postcontrast CT, and in 9 of the 12 by axial MRI. Thus, both postcontrast CT and MRI are relatively useful and complementary in the diagnosis of dural CCFs. Patients should be followed with selective cerebral arteriography for definitive diagnoses and for therapeutic planning.


Histochemical and contractile responses of rat medial gastrocnemius to 2 weeks of complete disuse. We studied the histochemical and in situ contractile changes in a rat ankle extensor, medial gastrocnemius, in which activation of muscle fibres by motoneurones was blocked for 14 days, using the sodium channel blocker tetrodotoxin applied to the sciatic nerve. Muscles were atrophied and showed slower twitch responses, greater fusion at subtetanic frequencies of stimulation, and higher twitch/tetanic ratios. Tetanic force/mm2 of fibre area and fatiguability were unchanged. Type II fibres were more atrophied and showed greater decreases in mitochondrial succinate dehydrogenase activity than type I fibres. The contractile changes resulting from complete disuse do not occur in models in which weight-bearing alone has been removed (space flight, hindlimb suspension), suggesting that the residual motoneurone activity reported in models of weightlessness is sufficient to prevent these responses. Similarly, the finding of a greater type II fibre susceptibility to complete disuse, which differs from the pattern seen in models of weightlessness, suggest that this residual motoneurone activity in the latter influences atrophic responses in a manner that is variable among motor unit types, to produce the reported preferential type I atrophy characteristic of removal of weight-bearing.


MRI versus CT and US in the evaluation of a patient presenting with superior vena cava syndrome. Case report. Three cross-sectional imaging modalities are compared in the evaluation of a patient with Superior Vena Cava Syndrome. The apparent and potential advantages of magnetic resonance imaging (MRI) over computer tomography (CT) and ultrasound (US) are discussed.


Role of the adrenal gland in the thermal response to morphine withdrawal in rats. Administration of naloxone to morphine-dependent rats results in an elevation of tail skin temperature and a fall in core temperature. Previous studies have demonstrated a role of the adrenal gland in the thermal responses that accompany morphine withdrawal in the rat. In the present study, experiments were designed to determine if the duration of adrenalectomy significantly influenced the thermal response observed in morphine withdrawal. In addition we evaluated the influence of the adrenal medulla and glucocorticoid replacement in adrenalectomized rats in mediating the thermal responses of the morphine-dependent rat. Ovariectomized rats were addicted to morphine and subsequently withdrawn by administration of naloxone. This treatment results in a significant rise in tail skin temperature and subsequent fall in colonic temperature. These thermal responses were not observed in morphine-naive rats. Adrenalectomy resulted in a significant attenuation of the rise in tail skin temperature associated with withdrawal. This reduced tail skin temperature response was not different among animals adrenalectomized for 1, 7, 14, 21, or 28 days. Likewise, the moderate increase in core temperature associated with morphine treatment was not observed in the adrenalectomized rats. Serum corticosteroid determinations confirmed the loss of the adrenal steroids in the adrenalectomized rats. In a subsequent experiment it was determined that adrenal demedullation did not reduce the tail skin temperature response during morphine withdrawal, and corticosteroids restored the naloxone-induced surge in tail skin temperature in morphine-dependent, adrenalectomized rats.(ABSTRACT TRUNCATED AT 250 WORDS)


Increased microalbuminuria in diabetic rats is independent of angiotensin II or glomerular proteoglycan synthesis. Increased microalbuminuria is seen early in rats with both streptozotocin-induced and genetic (Bio-Breeding) diabetes. This study examines the roles of angiotensin II-dependent mechanism(s) and sulfation of glomerular proteoglycans in this phenomenon, as both processes have been implicated by several lines of circumstantial evidence. Anionic sites in the glomerular basement membrane, attributed to the presence of heparan sulfate, were quantitated by polyethyleneimine staining at 15, 21, and 70 days of diabetes in rats treated with streptozotocin, with or without insulin, and at 70 days in the Bio-Breeding rats. All diabetic rats developed increased microalbuminuria: control, 0.08 +/- 0.03 microgram/mL glomerular filtration rate, mean +/- SD; streptozotocin without insulin at 15 days, 0.92 +/- 0.06 microgram/mL (p < 0.05); streptozotocin with insulin at 21 days, 0.61 +/- 0.37 microgram/mL (p < 0.05 vs. control). At 70 days, both the Bio-Breeding and the streptozotocin rats sustained their microalbuminuria to the same degree (p < 0.05 vs. control). Enalapril (250 mg/L) in the drinking water of diabetic animals did not reduce the microalbuminuria. Although the polyethyleneimine-stained heparan sulfate sites decreased significantly in the streptozotocin rats, they remained unchanged in the Bio-Breeding rats. To determine the cause of reduced heparan sulfate staining, the in vitro synthesis and degree of sulfation of proteoglycans by glomeruli isolated from control and streptozotocin diabetic rat kidneys were compared. The amount of heparan sulfate synthesis and degree of sulfation were unchanged in diabetic glomeruli, although lower incorporation into the extracellular matrix and greater secretion into the medium were noted.(ABSTRACT TRUNCATED AT 250 WORDS)


Role of spleen in ANF-induced reduction in plasma volume. Atrial natriuretic factor (ANF) causes an increase in hematocrit that cannot be accounted for by urinary losses. The mechanism behind this phenomenon was studied in intact and splenectomized rats. Rat ANF 99-126 was infused i.v. for 30 min into conscious rats at rates of 0 (saline control), 0.05, or 0.1 microgram/min. Plasma volume was then determined by dilution of the dye, Evan's Blue. In one group of rats, red cell volume was determined using 51Cr-labelled erythrocytes. ANF infusion was continued uninterrupted throughout the experiments. In the intact rats, ANF (0.10 microgram/min) caused hematocrit to increase from 38.9 +/- 0.5 to 41.2 +/- 0.4% (p < 0.005). Splenectomy so attenuated this response to ANF that it failed to reach significance. Similarly, ANF (0.10 microgram/min) caused plasma volume to fall from 5.1 +/- 0.1 to 4.5 +/- 0.1 mL/100 g body wt. (p < 0.005) in the intact rats, but did not affect plasma volume in the splenectomized rats. As a result, blood volume was significantly reduced by ANF in the intact rats, but remained unchanged in the splenectomized rats. Red cell volume did not change in response to infusion of ANF, nor did ANF affect the rate of clearance of Evan's Blue out of the plasma. It is concluded that the spleen is an important site of movement of protein-poor fluid out of the vasculature, and that this exchange is influenced by ANF.


Neurally mediated gastric mucosal damage in hypophysectomized rats. The role of the pituitary hormones in the development of neurally mediated gastric mucosal damage was examined in both normal and hypophysectomized urethane-anaesthetized male Sprague-Dawley rats. Gastric mucosal damage was elicited either by electrical stimulation of intact vagal nerves or by electrical stimulation in the paraventricular nucleus. Macroscopic damage was scored following the stimulation period and samples of the stomach were fixed for histological assessment. Damage scores were assigned based on a 0 (normal) to 3 (severe) scale. Control experiments in which the vagi were not stimulated did not result in any significant gastric damage in either normal (0.56) or sham surgery (0.14) animals, whereas hypophysectomized animals were observed to have significant damage (1.44, p < 0.05). Stimulation of the vagi in hypophysectomized animals resulted in damage that was not significantly different compared with the hypophysectomized control animals (1.25, p > 0.05). In normal animals, stimulation of vagal nerves resulted in mean damage scores of 2.00, values that were not significantly different from those observed in hypophysectomized animals (1.25, p > 0.05). Similarly, stimulation in the paraventricular nucleus of hypophysectomized animals resulted in gastric lesions (2.00) that were not significantly different from those observed in normal animals (1.91, p > 0.05). These data suggest that such neurally mediated gastric damage does not depend upon neurosecretory projections to the pituitary gland, but that the maintenance of an intact gastric mucosa under normal conditions requires the presence of pituitary hormones.


Characterization of a novel variant of amino acid transport system asc in erythrocytes from Przewalski's horse (Equus przewalskii). In thoroughbred horses, red blood cell amino acid transport activity is Na(+)-independent and controlled by three codominant genetic alleles (h, l, s), coding for high-affinity system asc1 (L-alanine apparent Km for influx at 37 degrees C congruent to 0.35 mM), low-affinity system asc2 (L-alanine Km congruent to 14 mM), and transport deficiency, respectively. The present study investigated amino acid transport mechanisms in red cells from four wild species: Przewalski's horse (Equus przewalskii), Hartmann's zebra (Zebra hartmannae), Grevy's zebra (Zebra grevyi), and onager (Equus hemonius). Red blood cell samples from different Przewalski's horses exhibited uniformly high rates of L-alanine uptake, mediated by a high-affinity asc1-type transport system. Mean apparent Km and Vmax values (+/- SE) for L-alanine influx at 37 degrees C in red cells from 10 individual animals were 0.373 +/- 0.068 mM and 2.27 +/- 0.11 mmol (L cells.h), respectively. As in thoroughbreds, the Przewalski's horse transporter interacted with dibasic as well as neutral amino acids. However, the Przewalski asc1 isoform transported L-lysine with a substantially (6.4-fold) higher apparent affinity than its thoroughbred counterpart (Km for influx 1.4 mM at 37 degrees C) and was also less prone to trans-stimulation effects. The novel high apparent affinity of the Przewalski's horse transporter for L-lysine provides additional key evidence of functional and possible structural similarities between asc and the classical Na(+)-dependent system ASC and between these systems and the Na(+)-independent dibasic amino acid transport system y+. Unlike Przewalski's horse, zebra red cells were polymorphic with respect to L-alanine transport activity, showing high-affinity or low-affinity saturable mechanisms of L-alanine uptake. Onager red cells transported this amino acid with intermediate affinity (apparent Km for influx 3.0 mM at 37 degrees C). Radiation inactivation analysis was used to estimate the target size of system asc in red cells from Przewalski's horse. The transporter's in situ apparent molecular weight was 158,000 +/- 2500 (SE).


Characterization of lipid intake into rabbit jejunal brush border membrane vesicles. The absorption of lipids is generally accepted to be mediated by a process of passive diffusion, although some recent data have raised the possibility of a mediated component. Brush border membrane vesicles (BBMV) have been widely used to study nutrient transport, but have only recently been used to examine the uptake of lipids. Using a BBMV technique validated with studies of the uptake of D-glucose, we examined the uptake of linoleic acid into the jejunum of adult rabbits. The uptake of 100 microM linoleic acid was constant between 2 and 20 min, with no overshoot observed at earlier periods. Linoleic acid uptake was suppressed by 88% with 0.6 mM phloridzin and by 58% with 0.2 mM phloretin, but uptake of linoleic acid was unaffected by the absence of sodium, by the presence of a sodium gradient, or by varying the osmolarity of the buffer. Lysis of the BBMV incubated with linoleic acid by the addition of ice-cold deionized water did not alter the amount of linoleic acid associated with the BBMV. The linoleic acid concentration curve was linear up to 160 microM, when carried out under initial rate conditions and in the presence of 2 mM taurocholic acid. These results are compatible with the process of passive uptake of linoleic acid into BBMV of rabbit jejunum, but do not exclude the possible physiological importance of a membrane fatty acid binding protein.


The role of migrating myoelectric complexes in the regulation of digesta transport in the preruminant calf. Four calves were equipped with an electromagnetic flow probe inside the transverse duodenum and with electrodes at intervals of 2 cm on either side of the probe. Amounts of 0.5, 2.0, 3.5, and 5.0 kg of whole milk were given according to a latin square design. Recordings of digesta flow and myoelectric activity were made during a 5.6-h period after feeding to quantify the influence of migrating myoelectric complexes on digesta flow through the transverse duodenum of preruminant calf under different levels of milk intake. Immediately after feeding, a phase of irregular spiking activity appeared; its length increasing linearly (p = 0.002) with the amount of milk fed. Increasing milk intake led to linear increases in duration (p = 0.001) and total electrical activity (p = 0.002) of the irregular activity phases, quadratic shortening of the quiescent phases (p = 0.021), and linear decrease (p = 0.006) in the numbers of migrating myoelectric complexes. Intermittent flows of digesta, each of them corresponding to a strong spike burst, appeared during irregular spiking activity phases. Augmentation of the milk ingested did not affect the volume of each gush of digesta but caused a cubic increase in the number of gushes (p = 0.023) and in the total volume of digesta (p = 0.009). These cubic effects implied that with increased intake of milk, the duodenum endeavoured to accelerate the flow of digesta in an attempt to return to an "empty state" in about the same time for all levels of milk consumed. This was achieved mainly through adjustments in the duration and activity of the irregular spiking activity phase.


Relationship of postprandial motilin, gastrin, and pancreatic polypeptide release to intestinal motility during vagal interruption. Experiments were performed to determine how postprandial motilin, gastrin, and pancreatic polypeptide plasma concentrations measured during vagal blockade relate to coincident small intestinal motility patterns. Feeding produced a postprandial pattern of intestinal motility coincident with a sustained increase in gastrin and pancreatic polypeptide and a decline in motilin plasma concentrations. Vagal blockade replaced the fed pattern with one similar to migrating motor complex (MMC) activity. Highest motilin plasma concentrations were observed during phase III of this MMC-like activity, as occurs in the fasted state. Vagal blockade reduced but did not abolish the postprandial increase in plasma gastrin and pancreatic polypeptide concentrations. Termination of vagal cooling produced a decline in motilin and an elevation in gastrin and pancreatic polypeptide concentrations, coincident with the return of the fed pattern. In conclusion, during vagal blockade in the fed state (i) motilin, but not gastrin or pancreatic polypeptide plasma concentrations, fluctuate with the MMC-like activity, and any measurement of motilin concentration under these circumstances must be interpreted on the basis of gut motility patterns, and (ii) gastrin and pancreatic polypeptide concentrations are marginally elevated, but these changes are not enough to disrupt the MMC or have any motor effect. Lastly, the fed pattern and the postprandial changes in motilin, gastrin, and pancreatic polypeptide concentrations are in part dependent upon intact vagal pathways.


Effects of gaseous anesthetics and ultrashort and short-acting barbiturates on human blood platelet free cytosolic calcium: relevance to their effects on platelet aggregation. The effects of elevated pressures (to 6 atmospheres absolute (ATA)) of nitrous oxide (N2O) and of xenon (Xe), and barbiturates on platelet free cytosolic calcium ([Ca2+]i) and platelet aggregation were studied. N2O inhibited the ADP-induced rise in [Ca2+]i whereas Xe had no effect. Neither affected basal levels. Pentobarbital and methohexital had little effect on basal or stimulated levels in the presence or "absence" of extracellular Ca2+; but both, at concentrations > 10(-4) M, inhibited platelet aggregation induced by adenosine diphosphate. Thiopental increased basal and stimulated [Ca2+]i when extracellular Ca2+ was present, but not when it was absent, and displayed a bimodal effect with low and high doses being more active than intermediate ones. It also potentiated aggregation. Methitural displayed similar, but nonsignificant, effects. These patterns held for all agents whether or not acetylsalicylic acid was present. Pentobarbital and methohexital inhibited phorbol myristate acetate aggregation in low extracellular calcium and no potentiation was seen with thiopental. In the absence of extracellular Ca2+, no potentiation was observed in stimulated platelets. Potentiation of aggregation previously reported for Xe does not involve increased Ca2+ uptake and did not occur in the absence of extracellular Ca2+. A common mechanism of action for these agents cannot be inferred from their effects on platelet aggregation or [Ca2+]i, as their pharmacological profiles differ markedly. It is evident that their inhibitory properties in this cell are not dependent on extracellular Ca2+, whereas the potentiation observed with pentobarbital, and formerly with Xe, is so dependent.


A mediator derived from arginine mediates inhibitory junction potentials and relaxations in lower esophageal sphincter: an independent role for vasoactive intestinal peptide. This study provides mechanical and electrophysiological evidence to show that a metabolite of arginine, not vasoactive intestinal peptide (VIP), is the putative nonadrenergic noncholinergic (NANC) inhibitory mediator in canine and opossum lower esophageal sphincters (LES). Relaxations of spontaneous active tension by electrical field stimulation (FS) at parameters that induced tetrodotoxin (TTX)-sensitive responses were abolished by L-N omega-arginine methyl ester (L-NAME) at 10(-4) M and restored by L-arginine (10(-3) M) but not D-arginine (10(-3) M). TTX-insensitive relaxations to 5-ms pulses were unaffected by L-NAME, L- or D-arginine. VIP (10(-6) M) caused maximum relaxations of basal tension in both the opossum and canine LES. However these relaxations, unlike those from FS were unaffected by L-NAME. Methylene blue (5 x 10(-5)M) increased basal tension of the LES in each species, and did not inhibit the relaxation to FS or VIP, but often increased the amplitudes of these responses due to the increase in basal tension. In parallel experiments NANC inhibition of body circular muscle from opossum esophagus was abolished by methylene blue. Electrophysiological studies using micro-electrodes revealed that NANC inhibition was associated with inhibitory junction potentials in the canine LES. These were inhibited by L-NAME and restored by L-arginine but not D-arginine. In contrast, 10(-6) M VIP in canine LES did not induce any change in membrane potential during a 20-min superfusion. Sodium nitroprusside also hyperpolarized sphincteric muscle and its effects were not affected by L-NAME.(ABSTRACT TRUNCATED AT 250 WORDS)


Regulation of glucose transport in isolated adipocytes by levamisole. When isolated rat adipocytes were incubated with increasing concentrations of levamisole (0.5-5 mM), basal glucose oxidation decreased by almost 50% and insulin-stimulated glucose oxidation decreased by 90%. The decrease in glucose oxidation correlated with an inhibition of glucose transport, since levamisole at 5.0 mM decreased basal 3-O-methylglucose transport by 60% and insulin-stimulated transport by 80%. Diamide-stimulated glucose transport was also inhibited approximately 80% by 5.0 mM levamisole. Levamisole at concentrations up to 5.0 mM had no effect on phosphofructokinase activity. The present results suggest that levamisole inhibits glucose utilization by inhibiting glucose transport in a concentration-dependent manner.


Regional intercostal activity during coughing and vomiting in decerebrate cats. Regional variations in the discharge patterns of the internal and external intercostal muscles of the middle and caudad thorax were studied in decerebrate, spontaneously breathing cats during coughing and vomiting. Coughing, induced by electrical stimulation of the superior laryngeal nerves, consisted of increased and prolonged diaphragmatic activity followed by a burst of abdominal activity. Mid-thoracic external and internal intercostal muscles discharged synchronously with the diaphragm and abdominal muscles, respectively. Caudal external and internal intercostal muscles, however, discharged synchronously with the abdominal muscles. Vomiting, induced by stimulation of the lower thoracic vagi, consisted of a series of synchronous bursts of diaphragmatic and abdominal activity (retching) followed by a prolonged abdominal discharge after the cessation of diaphragmatic activity (expulsion). Caudal external and internal intercostals discharged in phase with diaphragmatic and abdominal activity but both mid-thoracic intercostal muscles discharged out of phase with these muscles. These results indicate major differences in the control and functional roles of intercostal muscles at different thoracic levels during these behaviours.


A lament by women for "the people, the land" [Nishnawbi-Aski Nation]: an experience of loss. In response to a hunger fast by five members of the Sandy Lake Band at the Sioux Lookout Zone Hospital in Northern Ontario (Canada)--a cultural protest of the status of health care services in the Zone--the Federal Minister of Health agreed to establish a Panel to review the region's health care system. The year-long study involved hearings in each of the 28 remote communities of the Zone, and interviews with elders and chiefs, women, and health care providers. A consultation team from McMaster University (Faculty of Health Sciences) assisted the Panel with epidemiological survey research, literature reviews, and the interpretation of the data collected in the proceedings. This paper offers our interpretation of data collected from the qualitative study component. Specifically, it provides an interpretation of the discourse of the native women of the Nishnawbi-Aski Nation on their experience of health and health care. An "idiom of loss" captures, we feel, the depth of their concerns, dilemmas and frustrations.


Iron status and pregnancy in a northern Canadian population: relationship to diet and iron supplementation. To determine the extent of iron deficiency, the prognostic value of prenatal ferritin levels and the desirability of prenatal iron supplementation in the western Canadian arctic, dietary iron intake was determined in 171 women and ferritin levels determined in 121 women during pregnancy, 79 at delivery and 77 postnatally, as well as in 65 of their infants at birth and 74 postnatally. Iron deficiency (ferritin < 15 ng/ml) was present in 34% of women during the first two trimesters, 25% (20/79) at delivery and in 51.7% (15/29) of mothers and 31% (9/29) of infants beyond four months after delivery. Maternal follow-up ferritin levels correlated poorly with dietary iron intake but well with prenatal ferritin levels, which appeared to be good predictors of the effectiveness of supplementation. Mean infant follow-up ferritin levels were 105.6 +/- 115.2 ng/ml with, and 46.7 +/- 63.5 without maternal prenatal supplementation (p = 0.03); maternal, 45.5 +/- 40.9 ng/ml with, and 12.8 +/- 9.2 without (p < 0.001). Measurement of prenatal ferritin levels to determine risk of iron deficiency and routine prenatal iron supplementation are recommended.


Indian Reserve and registered Indian mortality in Canada. Although in demand, there is only limited information available regarding the patterns of mortality among Natives in Canada. Mortality rates for residents of Canadian Indian Reserves (IRs) and Registered Indians were calculated for the periods 1979-1988 and 1981 respectively. Proportionate mortality ratios and age-standardized mortality rates for residents of Indian Reserves were similar to those obtained for Registered Indians. Standardized mortality ratios were calculated using both Canadian mortality and mortality in selected isolated rural populations as references. Dramatically increased risks were observed among Native populations for mortality from alcoholism/liver cirrhosis, homicide, suicide and pneumonia. While SMRs calculated using mortality rates in rural populations appeared to be preferable to those using Canadian rates, the use of Canadian rates does not alter the conclusion that IRs have significantly elevated mortality from environmental and social causes which, although improving, require continuing control efforts.


Partner notification and patient education for cases of Chlamydia trachomatis infection in a rural Nova Scotia health unit. From September 1990 to March 1991, 47 of 52 patients with genital C. trachomatis infections in a rural health unit in Nova Scotia were interviewed about preventive education by physicians partner notification, past history, and treatment. Seventy-six percent of those with partners of the previous month were instructed by physicians to notify these partners. Twenty-five of 37 partners were notified. Of those not notified, 83% could have been reached. Reasons for cases not notifying partners included not being informed of test results, embarrassment, and not considering notification important. Fifty-two percent of cases were advised to practise safer sex; this was generally limited to advice to use condoms. Twenty-three percent had had a previous sexually transmitted disease. Treatment was appropriate in all cases where it could be determined. More preventive education by physicians and public health involvement in partner notification for such patients are required.


Women's exercise participation: the relevance of social roles compared to non-role-related determinants. The objectives of this study were 1) to determine the relationship between women's exercise participation and their social roles as well as characteristics of these roles, and 2) to determine the relative importance of social roles compared to non-role-related determinants (including social support, perceived barriers, interest in exercise, and perceived importance of exercise). A cross-sectional survey was done among 1,113 randomly selected urban women aged 20-49. Social roles did not emerge as a major risk factor for exercise participation. Statistical modelling indicated that whether women exercise was only related to role overload in the presence of the non-role-related determinants. For women exercising, parenthood as well as role overload were related to the amount of exercise in the presence of the non-role-related determinants. These findings have important implications for exercise promotion for women.


A pilot study assessing the health status of the Hispanic American community living in Vancouver. We undertook a pilot study in order to obtain baseline health information on the Hispanic American Community in Vancouver and to evaluate the feasibility of research in this community. We used the Interviewer Administered Questionnaire and the Lifestyle and Your Health Questionnaire from the Canada Health Survey [CHS]. Questionnaires were translated into Spanish and back into English. Descriptive analyses were similar to the CHS and focussed on health services utilization, lifestyle practices and psychological parameters. 43.3% of males and 12% of females did not have any medical consultation in the previous 12 months; 100% of respondents stated that high cost did not allow regular dental care; 23.3% of males and 28.6% of females experienced anxiety and depression; 26.2% of females did not known how to do breast self-examination. Significant potential health problems exist in this community particularly related to stress, lack of preventive behaviour and low utilization rates. Further research in this community is possible, but hampered primarily by a reluctance to participate because of concerns regarding privacy and immigration status.


[Stress and social support in relation to psychological distress in community-residing elderly persons in Montreal]. Our aim was to quantify the degree of association that selected psycho-social and health variables have with psychological distress in the elderly. In order to estimate the level of association, data previously obtained from the "Enquêre Santé Québec" (1987) were entered into a multiple regression analysis with psychological distress as the dependent variable. The independent variables retained were: age, sex, language, physical health, functional health, health status perception, social integration, perceived social support and stress. The scores contained in the data bank were from a representative sample of subjects (n = 361, age = 72.7 +/- 6.3) living in the Montreal area. The results of the regression analysis indicated that psychological distress is significantly related (adjusted R2 = 0.256; p = .000) to the following variables: the interaction "stress events X perceived social support", physical health, functional health and sex. The results of the present study consequently support previous reports relating psychological distress to physical health, social support, stress and sex with a predominant effect on women. Finally, the results give further support to the "buffering effect" of social support on stress.