The fine structure of the feline superior vestibular nucleus: identification and synaptology of the primary vestibular afferents.

The superior vestibular nucleus of the cat and its primary vestibular efferents were examined by light and electron microscopy. The primary vestibular afferents branch within the nucleus in a sheet-like pattern, in the transverse plane. The dendritic fields of many secondary neurons are shaped like discs and are also oriented in the transverse plane. This relation between the primary afferents and dendritic fields may be relevant to the convergence of primary afferents innervating particular endorgans onto secondary neurons. Synaptic boutons in the SV were divided into 3 putative types on the basis of the size and shape of their synaptic vesicles. The primary afferent bouton was identified by comparing the SV of the two sides after unilateral lesions of the vestibular ganglion. Its boutons contain round vesicles of 40 nm average diameter and are associated with prominent postsynaptic densities; the two other putative bouton types contain smaller, round vesicles, and pleomorphic vesicles. The primary afferent boutons largely contact proximal dendrites, their appendages, and cell somata of the secondary neurons. In animals receiving unilateral lesions of the vestibular ganglion and allowed to survive long enough for the primary afferent boutons to disappear (5--6 days), there occurs in the denervated as compared to normal SV: (1) a decrease in the fraction of the somal surface of the secondary neurons covered by boutons with small round vesicles; and (2) a decrease in the ratio: number of boutons with small round vesicles to number of boutons with pleomorphic vesicles. In addition, there appears on the lesioned side a new group of boutons with pleomorphic vesicles smaller than those in boutons from the control side. These observations suggest plastic changes in response to deafferentation, and may be related to the marked behavioral recovery which occurs within a few days after lesion of the vestibular ganglion.


The bilaminar and banded distribution of the callosal terminals in the posterior neocortex of the rat.

After callosal sectioning, the callosal connections of the posterior neocortex of the rat cerebral hemisphere were demonstrated using the Fink-Heimer technique. Serial frozen sections of the whole brains were cut in transverse, horizontal, and tangential planes. In tissue sections, degenerating terminals were concentrated in two distinct laminae within the depth of the cortex. In addition the terminals had a patchy distribution. The degeneration was marked on projection drawings of serially arranged sections, and subsequent reconstruction showed the terminal degeneration to be distributed in bands. Five dorsoventrally oriented bands of terminals were present in areas 39, 41 and 36 collectively, and a rostrocaudal band in area 20. In area 17 terminations were apparently absent except at its borders with areas 18, 18a and 7. The degenerating callosal terminals within these areas produced a circumferential band around area 17. The findings are discussed with respect to the significance of these patterns of corticocortical connections.


Orthodromic activation of hippocampal CA1 region of the rat.

(1) The posterior alveus (PA), the anterior alveus (AA) and the Schaffer collaterals (SCH) evoked field potential components which were organized as parasagittal strips of various widths. Spatially continuous and interactive lamellae are suggested. (2) By correlation with unit activities, the early postsynaptic components evoked by PA, AA and SCH were inferred to be extracellular excitatory postsynaptic potentials (EPSPs) and the late, long-duration components, the inhibitory postsynaptic potentials (IPSPs). The hypothesis that interneurons as well as pyramidal cells generate the field is proposed and discussed. (3) One- and two-dimensional profiles of deep evoked potentials and current source-sink analysis revealed excitatory synapses in stratum oriens for the PA and AA inputs and in stratum radiatum for the SCH input. The late dipole field evoked by PA and AA possessed current sources in strata radiatum and pyramidale, the sites of the inhibitory synapses. The late dipole field evoked by SCH had another component possibly generated by recurrent activity, afterpotentials or relayed activity through CA3.


Functional effects of lesion-induced plasticity: long term potentiation in formal and lesion-induced temporodentate connections.

The crossed temporodentate pathway from the entorhinal cortex of one hemisphere which proliferates in response to a contralateral entorhinal lesion in adult rats was analyzed for its ability to exhibit long term potentiation of synaptic efficacy similar to that which occurs in the normal ipsilateral temporodentate pathway. It was found that while the small synaptic response evoked by contralateral entorhinal cortical stimulation in normal rats does not undergo long term potentiation, after unilateral entorhinal lesions and proliferation of the crossed temporodentate pathway, the crossed pathway acquires a capacity for potentiation of synaptic action which qualitatively resembles that of the normal ipsilateral temporodentate circuit. However, despite the potentiation of synaptic drive, no long term enhancement of cell discharge was observed in the re-innervated dentate gyrus even through potentiation of this parameter was very prominent in the ipsilateral pathway. Mechanisms are discussed by which a previously non-potentiating pathway may acquire, as a consequence of lesion-induced sprouting, an ability to undergo long term potentiation of synaptic efficacy in a fasion similar to the ablated pathway. Reasons for the failure to observe potentiation of cell firing are also considered.


Acute dendrotoxic changes in the hippocampus of kainate treated rats.

Kainic acid (KA), a potent neuroexcitatory and neurotoxic analog of glutamate (Glu), induces a widespread pattern of brain damage when administered subcutaneously to adult rats. The hippocampus is among the brain regions most consistently and severely damaged. Here we describe acute swelling of certain spines and branchlets of dendrites as the first detectable sign of KA neurotoxic changes in the hippocampus. These swellings conform to a laminar pattern suggesting selective toxic interaction of KA at specific levels of the dendritic trees of hippocampal pyramidal and dentate granule neurons. The frequency and severity of involvement of each type of hippocampal neuron at each level of its dendritic tree was roughly estimated and neuronal types were ranked from the most to least extensively involved (CA3 greater than CA4 greater than CA1 greater than CA2 greater than dentate granules). The same rank order has been described for the vulnerability of these neurons to acute destruction following intraventricular KA administration. Because the pattern of dendritic dilatations observed corresponds well with the pattern of termination of putative glutamergic inputs to the hippocampus, we interpret the findings as being consistent with the hypothesis that the toxic effects of KA are mediated through glutamergic excitatory receptors. We propose that the sensitivity of a given neuron to the neurodestructive action of KA may be determined by the percentage of its dendritic surface occupied by Glu receptors. We suspect that most, if not all, hippocampal neurons receive some glutamergic input and, therefore, are sensitive to KA. That CA3 pyramids are substantially more sensitive than dentate granules may signify that the former receive many more Glu terminals than the latter, an assumption quite consistent with our observation that focal dendritic swellings were both more densely and more widely distributed over the dendritic surfaces of the former than the latter.


Quantitative studies of neuronal RNA on the subiculum of demented old individuals.

Autopsied human brains from three patients with senile dementia were studied for the effect of neurofibrillary tangles on neuronal RNA content. Nerve cell bodies were dissected out from the subiculum under the phase contrast microscope and were separated into two groups based on the presence or absence of neurofibrillary tangles within the perikaryon. It was found that the mean RNA content of the tangle-bearing cells was 28.61 pg, whereas that measured in nerve cell bodies considered as free from the tangles was 41.21 pg. Thus, a significant decrease in neuronal RNA content could be correlated to an excess accumulation of neurofibrillary tangles.


Receptive fields of neurons in areas 17 and 18 of tree shrews (Tupaia glis).

Receptive fields of 245 cells in areas 17 and 18 were explored in tree shrews. Cells with simple and complex receptive fields were found in both areas but with different statistical distriubtions. A small percentage of non-oriented fields were found to be binocularly activated in both areas. Cells in area 17 preferred dark over light stimuli. Selective for direction, speed of stimulus movement, and level of background illumination, as well as combinations of these were common. Few hypercomplex cells were found. The superior retention of visually guided behavior of three shrews after lesions of the striate cortex is not explained by any radical difference between the properties of their striate neurons and those of other mammals.


Removal of 14-C-palmitate during ventriculocisternal perfusion in conscious dogs in insulin-induced hypoglycemia.

A detailed description of a method is presented allowing continous ventriculocisternal perfusion of metabolites in the conscious dog. Using this preparation, the loss of the infused albuminbound 14-C-aplmitate, was studied in 14 conscious dogs during ventriculocisternal perfusion with artificial cerebrospinal fluid (CSF). Forty-five percent of the infused 14-C-palmitate was recovered from the cisternal effluent under equilibrium conditions after 60 min of perfusion. The effect of the injection of 2.0 U insulin/kg was also investigated in seven dogs. Plasma glucose concentration decreased to 40--50 mg% and the amount of 14-C-palmitate recovered was significantly higher one hour after insulin compared to the controls receiving saline injections. No significant changes in cerebral arteriovenous differences of glucose or oxygen or in venous 14-C-palmitate concentration were observed during the same time. It is concluded that the combined use of ventriculocisternal perfusion and the analysis of cerebral arteriovenous differences are useful in studying brain metabolism in the consciuos dog.


The involvement of the olfactory bulbs in the regulation of gonadal and thyroidal activities of male red-winged blackbirds, exposed to short-day light regime.

Surgical removal of the olfactory bulbs (OB) was performed in mature male red-winged blackbirds, maintained under a short-day light regime. Bulbectomy caused hyperphagia, which was not accompanied by obesity. Bulbectomized (OBX) birds had incresaed thyroid follicular activity and had greater developed testes than sham-operated controls. In the adenohypophyses of the OB-removed birds there was an increase in the populations of 4 types of chromophils: alcianophils, PAS-positive basophils, orangeophils and PAS-positive acidophils. The possibility that the OB are involved in the photoperiodic regulation of the activity of the gonads and thyroids is discussed.


Effect of cycloheximide on temperature regulation in rats.

The effect of cycloheximide, an inhibitor of protein synthesis, on temperature regulation in afebrile rats was studied to determine whether its reported antipyretic effect might be attributable to a non-specific antimetabolic effect. Within 60 min after administration of cycloheximide (5 mg/kg IP) to female rats at ambient temperatures of 34, 25 and 15 degrees C, a significant decrease in colonic temperature was observed as compared with control rats administered saline IP. Measurements of rate of oxygen consumption showed that cycloheximide (5 mg/kg IP) significantly depressed the ability of rats to increase their heat production during a cold stress (15 degrees C). In the cold the rate of oxygen consumption increased 8.7 +/- 0.8 ml/min/kg0.75 in the control rats but only 1.8 +/- 0.9 ml/min/kg0.75 in the cycloheximide-treated rats. Since the thermoregulatory changes accompanying cold stress are similar to those observed during the genesis of fever, these data suggest that cycloheximide may have a general depressant effect on heat production rather than a specific antipyretic effect.


Brainstem correlates of gustatory similarity in the hamster.

Responses of neurons in the nucleus tractus solitarius (NTS) and parabrachial pons (Pb pons) of the hamster to 10 gustatory stimuli were compared to behavioral similarities among these compounds. Animals were given a conditioned taste aversion to one of the 10 stimuli by pairing it with an induced gastrointestinal illness. Following this procedure, the degree of generalization of the learned taste aversion to each of the other compounds was measured. Behavioral similarity profiles were derived for each stimulus from the similarities in the generalization profiles of each pair of compounds. The across-neuron correlations in the firing rates evoked by these stimuli in the NTS cells corresponded quite well to these behavioral profiles, as did these neural correlations among Pb pontine cells, except for those correlations involving quinine. Sucrose-best cells in the Pb pons are too broadly responsive to account for the behavioral similarity functions for sweet-tasting stimuli, although other best-stimulus categories of cells (NaCl- and HCl-best) showed response profiles quite similar to the behavioral profiles, as did all best-stimulus classes of cells in the NTS.


Septal destruction in infant rats and the ontogeny of drinking behaviors.

Male and female albino rat pups sustained septal destruction at 10 days of age and body weight and water intakes were measured daily throughout development until 200 days of age. During development the septal and control rats received a battery of drinking tests (e.g., cellular dehydration, hypovolemia, renin). Septal rats (males and females) were hyperdipsic for daily water intakes as early as 31 days of age and the daily hyperdipsia persisted through 200 days of age. On the battery of drinking tests, septal rats consumed water at control volumes on all tests except water deprivation (following which females were hyperdipsic) and food deprivation (during which both males and females were hyperdipsic). Urine output-water intake relationships were determined, and a series of food deprivation tests were conducted during development to determine the etiology of the developmental septal hyperdipsia. All results suggest that hyperdipsia associated with septal destruction during the preweaning period is a primary condition and not secondary to altered output mechanisms, abnormal feeding-drinking patterns, or displacement behavior.


A bipolar electrode for peripheral nerve stimulation.

The construction of a bipolar electrode for the stimulation of peripheral nerves is described. The electrode was designed for acute stimued in which the effects of peripheral nerve stimulation on central neural activity in rats were determined. Since the electrode can be secured into a fixed position, neural recordings can be made during the stimulation of various visceral nerves and the electrode can be easily adapted for chronic behavioral studies.


Morphological evidence that reline SMR and human mu are analogous rhythms.

In cats implanted with epidural screw electrodes over sensorimotor cortex, various recording montages were used to observe the waveform of the sensorimotor rhythm (SMR). It was found that in bipolar recordings spanning the crus, SMR exhibited a wicket-shaped waveform comparable in shape and polarity to the human mu rhythm. Based on previously reported topographic and functional similarities of feline SMR and human mu, and on the present data demonstrating morphological similarities, it appears that feline SMR is the first proven feline model of a spontaneous human ieeg rhythm.


Tapered tungsten fine-wire microelectrode for chronic single unit recording.

A new fine-wire microelectrode made from tungsten wire is described. The electrode design provides for strength as well as flexibility due to the stiffness of tungsten wire and a gradually tapering profile. Unlike previously-used fine wire electrodes, microelectrodes of the new design can be singly implanted under electrophysiological control into deep brain structures of larger animals such as cats. The flexibility of the fine diameter terminal portion of the microelectrode permits stable recording from caudal brain stem single units during vigorous behavioral activity.


A minimum component AM transmitter to monitor electronic brain stimulation.

Construction of a light weight AM transmitter which can be used to monitor implanted electronic brain stimulators is described. The unit can operate continuously for 40 hours on a single battery and can easily be carried by a small laboratory animal. The range of the unit is limited to approximately 1 meter and the transmitted signal can be detected by a standard AM broadcast band receiver. The unit is simple to construct, inexpensive, and reliable in performance.


Evoked potential correlates of stable inter-individual differences in rat behaviour.

Individual differences in rats' exploratory behaviour are stable over time, suggesting inherent differences in brain mechanisms for handling sensory information. These differences may have a neurophysiological basis since a negative correlation was found between individual variation in exploratory behaviour and recovery functions of cortical visual evoked potentials. Recovery functions were an expression of the extent to which the visual system recovered its responsiveness following initial stimulation. They were obtained by using pairs of flash stimuli separated by 3 interstimulus intervals (ISIs): 100, 200 and 300 msec. Recovery was defined as the amplitude of the response to the second flash expressed as a proportion of the response to the first flash. Only short latency components of the evoked responses were considered. The mean value for recovery averaged over the three ISIs constituted the recovery function. Only responses recorded when rats were quiet but alert were used for analysis. Evoked potential recovery functions appear to reflect a neurophysiological mechanism underlying the different capacities of individual rats for responding to novelty.


Effects of feedback caudate nucleus stimulation on spontaneous fast amygdaloid spindles and drive.

Experiments with single and repetitive stimulation of the head of the caudate nucleus (4-10 V, 0.3 msec) triggered by occurrence of fast amygdaloid spindles (35 c/s microV, 0.5 sec) were performed in six animals with chronically implanted cerebral electrodes. In conjunction with the anterior cortical recruiting response the stimulation increased the incidence of amygdaloid fast spindles and decreased the incidence of hippocampal theta activity and of searching eye movements. The associative training failed, however, to significantly modify in the background EEG, the mean incidence of the fast amygdaloid spindles or the rate of the sensorimotor rhythm of 12-18 c/s. Its only effect (after long repetition) was a displacement to the right of the regression line of the incidence of the two rhythms and a slight alteration in the slope. The possibility of activating the caudate nucleus inhibitory effects through the amygdala during internal inhibition phenomena is discussed.


Afferent projections to the self-stimulation regions of the dorsal pons, including the locus coeruleus, in the rat as demonstrated by the horseradish peroxidase technique.

Afferent projections to the dorsal pons of the rat have been studied using the horseradish peroxidase (HRP) technique. HRP injections were made in each of the following regions: the vicinity of the locus coeruleus (LC); the periventricular gray, medial to the LC; the medial parabrachial region, lateral to the LC; the ventral cerebellum, dorsal to the LC; and the pontine reticular formation, ventral to the LC. Because intracranial self-stimulation (ICSS) has been obtained in these regions, the afferents have been discussed in terms of their possible contributions to the behavior. Previous ICSS studies of the dorsal pons have focussed on the LC as playing a central role. Presently identified inputs to the LC include: the dorsal raphe nucleus: the ventrolateral periaqueductal gray: the pontine reticular formation: the areas that contain the pontine and medullary noradrenergic and adrenergic cell groups: the lateral hypothalamic area: the contralateral LC: the deep cerebellar nuclei: the ventrolateral and parafascicular thalamic nuclei: and the parabrachial regions of the pons and midbrain.


Histoenzymological mapping of alkaline phosphatase and 5-nucleotidase in the medulla oblongata of a microchiropteran bat (Taphozous melanopogon Temminck).

The contribution deals with the distribution of alkaline phosphatase and 5-nucleotidase in the medulla oblongata of Taphozous melanopogon (a Microchiroptera), for the first time. The main highlights of the study are: (1) Cranial nerve nuclei demonstrate intense activity of alkaline phosphatase, whereas except nucleus tractus spinalis n. trigemini, rest of the nuclei show much variations of 5-nucleotidase distribution. (2) The vestibular nuclei are very intensely positive for 5-nucleotidase but exhibit variable activity of alkaline phosphatase. (3) Three subdivisions of nucleus olivaris inferior, i.e. nucleus olivaris accessorius medialis, nucleus olivaris accessorius dorsalis and nucleus olivaris inferior, which were not reported in the earlier neuroanatomical studies, have been identified. These nuclei show very intense alkaline phosphatase and relatively less intense 5-nucleotidase activities. (4) In general, the activity of alkaline phosphatase is stronger in neurons than in neuropil and that of 5-nucleotidase is stronger in neuropil than in neurons. (5) Blood capillaries are completely negative for alkaline phosphatase and intensely positive for 5-nucleotidase. A comparison is made between the distribution of these enzymes in the medulla oblongata of bat and other mammals so far studied.


The effect of medial preoptic--anterior hypothalamic lesions on bisexual behavior of the male rat.

The effects of bilateral radiofrequency lesions in various parts of the medial preoptic area (mPOA) and anterior hypothalamus (AH) on masculine and hormone induced feminine sexual behavior was studied in male rats. Anatomical as well as statistical analysis of the extent and location of the lesions and the consequent behavioral changes indicated that different parts of the mPOA-AH continuum are involved in masculine and feminine sexual behavior in different ways. Bilateral destruction at the transition of the mPOA and AH resulted in a large reduction of masculine sexual activity while lesions concentrated in the AH slightly facilitated feminine sexual behavior in males. These results are consistent with the notion that the mPOA-AH continuum is divided into anatomically and functionally different parts.


Lesions of the preoptic area facilitate lordosis behavior in male and female guinea pigs.

Male and female guinea pigs received radiofrequency lesions in the medial preoptic area (MPOA). Animals were gonadectomized, treated with estrogen and progesterone, and tested for the occurrence of the lordosis response to manual stimulation. Females with MPOA lesions exhibited enhanced lordosis behavior, shorter latencies to heat, longer duration of heat and longer maximum lordosis duration than sham control females. In males with MPOA lesions, the lordosis response could be elicited by manual stimulation, in contrast to no response in the sham control males. Furthermore, MPOA-lesioned males were insensitive to the inhibitory effects of progesterone on lordosis behavior, while MPOA-lesioned females were as sensitive as sham controls to the inhibitory effects of progesterone. The results suggest that a neural mechanism resides within the MPOA which inhibits the occurrence of lordosis behavior in both male and female guinea pigs and which is not involved in a sexual dimorphism in responsiveness to progesterone.


Fastigial modulation of brainstem behavioral mechanisms.

Stimulation of the rostral, but not caudal, half of the cerebellar fastigial nucleus was found to induce coordinated eating and grooming behaviors in the cat. These behaviors persisted, unchanged, after lesions of the ascending fastigial projections in the superior cerebellar peduncle, suggesting that such behaviors are produced by direct fastigio-bulbar pathways. These results support the suggestion that there is a close anatomical association between fastigial systems mediating elicited behaviors and those mediating fastigial pressor responses. The present results are also consistent with the growing view that cerebellar systems can exert important modulatory influences on neurobehavioral mechanisms.


Influence of electrical stimulation of the substantia nigra on spontaneous activity of raphe neurons in the anesthetized rat.

Recent studies of afferent connections of the anterior raphe using the horseradish peroxidase technique have demonstrated a major projection originating in the substantia nigra (SN). The present acute electrophysiological study examined the influence of stimulation of the afferent on the activity of individual neurons in the raphe of the posterior midbrain and anterior pons (n = 51), and of a control group of cells (n = 15) located 2 mm lateral to the raphe. The predominant effect of SN stimulation at 0.1-1.0 mA, 1 Hz or 10 Hz, was suppression of raphe activity, with 63% of the cells showing cessation of firing following SN pulses and only 8% showing excitation. The average duration of suppression was 200 msec at 1 Hz and 38 msec at 10 Hz. In contrast, 40% of the lateral cells were excited, with 27% of the cells showing suppression. The mean duration of total suppression of lateral cell firing was 61 and 17 msec at 1 and 10 Hz, respectively. The results from the raphe cells are consistent with recent reports of stimulation of other forebrain and brainstem afferents to the raphe in which suppression of raphe activity was the main effect.


Mapping of sensory-responsive cells in the septal area of the rat.

A study of sensory-responsive characteristics of single cells of the septal area of male rats was undertaken to determine the distribution of stimulation-induced changes in septal activity. Single cells were systematically sampled in six planes transecting the rostral-caudal axis of the septal area and were tested for responsiveness to visual, auditory, tactual, gustatory and olfactory stimuli. Approximately 50% of the sampled population of septal cells was responsive to at least one stimulus. Most of the responses of septal cells to stimulation were excitatory and occurred at the onset of stimulation. Regions of concentration of sensory-responsiveness cells in the system were found to lie in medial areas of the septum consisting of the dorsomedial portion of the lateral septal nucleus, the medial septal nucleus and the ventral portions of the medial and lateral nuclei. Visual, auditory and tactual stimuli were most effective in producing changes in spontaneous activity of units in these regions. On the basis of relationships of the medial septal region to other limbic areas having sensory-responsive properties, it is concluded that the medial septal area is one component of a limbic sensory system.


A rapid and simple cannulation technique for repeated sampling of cerebrospinal fluid in freely moving rats.

A cannulation technique for frequent sampling of cerebrospinal fluid (CSF) in unanaesthetized freely moving rats is described. A permanent stainless steel cannula, constructed in such a way that no loss of CSF occurs, is placed into the rat's cisterna magna and fixed to the skull by anchoring screws and dental cement. A special CSF outflow opening of the cannula is connected to polyethylene tubing for CSF sampling. Amounts of 50-150 microliters CSF can be collected repeatedly without any sign of disturbing the animal. The technique lends itself not only to pilot studies in which within a short period of time a large amount of CSF is wanted, but also to experiments in which physiological conditions are required.


Differential hypothalamic self-stimulation behaviour in Roman high-avoidance and low-avoidance rats.

Monopolar electrodes were implanted bilaterally and symmetrically into a small well defined region of the posterior lateral hypothalamus in 11 rats of the selected strains Roman high-avoidance (RHA/Verh, 6 animals) and Roman low-avoidance (RLA/Verh, 5 animals). Intracranial electrical stimulation (ICS) was used to study possible strain difference with respect to self-stimulation behaviour. Using a shuttle-box, the experimental set-up allowed measurements of the animal's preference, aversion, neutrality or ambivalence towards the stimulus. For both rat strains 10 electrode sites were tested with identical stimulation currents (100-600 microA in increments of 100 microA). Significant differences between the selected strains were found for preference (self-stimulation) and aversion: RLA/Verh-rats showed self-stimulation at lower stimulation currents than RHA/Verh-rats. At higher currents, both strains showed similar self-stimulation performance. RLA/Verh-rats escaped more often from ICS yielding self-stimulation at five of the six current levels. It is concluded that, in comparison with the RHA strain, RLA/Verh-rats are more sensitive to aversive effect of lateral hypothalamic stimulation. This seems to be associated with an increased sensitivity to the rewarding effects of such stimulation.


Latency distribution from orthodromic stimulation at the optic nerve, in the lateral geniculate nucleus and superior colliculus of rabbits.

Latency distribution of responses to optic nerve stimulation has been compared between the Lateral Geniculate Nucleus (L.G.N.) and Superior Colliculus (S.C.), in rabbits. Histograms revealed that in both structures the latency distributions are very similar. Results suggest that all groups of retinofugal fibers project to both sites, although longer latencies are more frequently met at the collicular level. In addition evidence is presented that in rabbit's optic nerve there are at least three populations of axons with different conduction velocities.


Effects of ovarian hormones on levels of luteinizing hormone in plasma and on serotonin concentrations in discrete brain nuclei.

Levels of serotonin were measureed in microdissected, individual brain nuclei in ovariectomized rats after treatment with ovarian hormones. Regions sampled included nuclei in the forebrain, rostral and medial hypothalamus, and midbrain tegmentum. Estradiol benzoate decreased levels of luteinizing hormone in plasma but did not affect serotonin levels in any region. Progesterone alone elevated serotonin content in the nucleus tractus diagonalis and ventral tegmental area. The combined estrogen plus progesterone regime produced a surge in plasma luteinizing hormone and also markedly elevated serotonin in the median eminence. These results may be of significance for ovarian hormonal regulation of gonadotropin secretion and reproductive behavior.


Elevation of calcitonin immunoreactivity in the pituitary and thyroid glands of genetically obese rats (fa/fa).

This paper contains the first demonstration of quantitative changes in the levels of calcitonin-like immunoreactivity in the pituitary. The concentration of calcitonin-like material in lean Zucker rats (?/+) was 0.42 +/- 0.09 ng/mg wet weight of pituitary. The pituitaries of obese rats (fa/fa) contained significantly greater levels (1.56 +/- 0.56 ng/mg wet weight). This 271% increase represents the first indication that pituitary calcitonin-like material may have a physiological role in genetically obese rats. Thyroidal calcitonin also elevated in the obese (111%). These large elevations in the calcitonin content of the glands of obese rats were not accompanied by significant elevations of calcitonin in the blood. This suggests that obese rats have problems with mechanisms for the release of calcitonin into the blood and might not be able to combat hypercalcemia as effectively as leans. However, this hypothesis remains to be tested.


Determination of picogram levels of brain serotonin by a simplified liquid chromatographic electrochemical detection assay.

A simplified assay is described for measurement of picogram amounts of serotonin (5-HT) by high pressure liquid chromatography with electrochemical detection (LCEC). The procedure involves pre-purification of brain 5-HT by adsorption on Amberlite CG-50. Serotonin is subsequently resolved and detected by LCEC on Zipax SCX resin. The present method gives working sensitivities of at least 100 pg, tissue recoveries of 95% and very low interassay variability (coefficient of variation = 3%). Determination of rat brain area 5-HT by this LCEC method is described and compared to other high sensitivity methods.


Distribution of norepinephrine and dopamine in cerebral cortical areas of the rat.

Concentrations of norepinephrine and dopamine were determined using enzyme isotope assay in 27 microdissected cerebral cortical areas of the rat. A detailed map is presented for microdissection of rat cerebral cortex. Norepinephrine was found in low but still measurable quantities throughout the cortex. Differences between cortical areas are also low. Relatively highest levels were demonstrated in the pyriform, insular and entorhinal cortices. The distribution of dopamine was found to be uneven with a maximal regional difference of 1:24. Concentration of dopamine was in all areas lower than that of norepinephrine. The highest dopamine concentration (2,4 ng/mg protein) was measured in the rostral pyriform cortex but other mesocortical (cingulate, frontal, insular and entorhinal) dopaminergic areas also contained relatively high amounts. Except for the caudal occipital and caudal entorhinal cortices all regions studied contained measurable quantities of dopamine. Its low concentration relative to norepinephrine (below 15%) suggests that in the cortical areas studied dopamine is present as the precursor of norepinephrine.


Taurine, analogues and ethanol elicited responses.

The effect of taurine, of some of its precursors and major metabolic products on spontaneous locomotor activity were studied in mice. The effect of taurine and some analogues on certain ethanol-mediated responses were observed. Administration of taurine, 50 mg/kg, IP, did not significantly alter motility in experimental animals compared to controls. Behavioral depression was evident subsequent to injection of cysteine hydrochloride or taurocholic acid (50 mg/kg). Administration of taurocholic acid, 50 mg/kg, IP, 30 min prior to a narcotic dose of ethanol, 5 g/kg, IP, reduced the time required for the onset of ethanol-narcosis. Pretreatment with cysteic acid, 50 mg/kg, IP, prolonged ethanol-produced narcosis. Treatment with cysteic acid 30 min prior to ethanol, 2.5 g/kg, IP, was found to decrease whole blood ethanol concentration as compared to the respective controls without a concomitant changes in brain ethanol levels. Administration of taurocholic acid, 100 mg/kg, IP, decreased the intake of an ethanol solution in rats preferring 5% ethanol solution over water as the drinking fluid of choice. None of the compounds tested altered endogenous specific activity of mouse liver alcohol dehydrogenase when given once daily (50 mg/kg, IP) for 10 consecutive days. The results suggest that both taurocholic acid and cysteic acid exert additive action to some ethanol-elicited responses studied.


Effects of morphine on hippocampal cells recorded in vitro.

Intracellular recordings from CA1 pyramidal cells were obtained in the in vitro hippocampal slice preparation before and after the application of morphine sulfate. Two distinct effects were observed following addition of morphine (1.0 mM) to the bathing media, or application to individual slices through pressure ejection via large tipped pipettes. Within 3-10 min following morphine application CA1 cell membrane potentials began to depolarize (5-10 mV) toward firing threshold. Spontaneous discharge rates were increased and nonactive cells became active. Rhythmic firing at a rate of 5-8 Hz was observed for 30-40 min following drug application. The spontaneous rhythmic firing could be partially reversed by the addition of naloxone (0.1 mM) to the bathing media. The second effect of morphine was to potentiate the development of epileptiform discharges in CA1 cells in response to low frequency orthodromic synaptic stimulation. The findings indicate that morphine alters the excitability of hippocampal pyramidal cells and such changes are likely to be mediated by opiate specific alterations in membrane conductance and/or tonic inhibitory synaptic inputs.


Morphine induced increases in the incorporation of 3H-thymidine into brain striatal DNA.

3H-thymidine uptake into DNA fractions of rat brain regions was measured following in vivo administration of (methyl-3H)-thymidine and morphine. Acute morphine administration (10 mg/kg; 30 min prior to 3H-thymidine) increased incorporation of 3H-thymidine into DNA of rat striatum. This effect was antagonized by naloxone (1 mg/kg). Further, the observed change in incorporation of 3H-thymidine into DNA in striatum could not be accounted for by differences in the local availability of the label in morphinized rats. An autoradiographic study revealed that the 3H-thymidine was localized in nuclei in cells of the sub-ependymal layer lining the lateral ventricles, an area of glial cell proliferation in adult rats. No change in 3H-thymidine incorporation into DNA was observed in any area of the brain in morphine-addicted rats or in rats undergoing naloxone-precipitated withdrawal. The results indicate that opiates may induce permanent anatomical changes in the brain, including alterations of neuroglial interactions.


Cerebellar actions on cochlear microphonics and on auditory nerve action potential.

The influence exerted by cerebellar stimulation upon cochlear microphonics (CM) and auditory nerve action potential (AP) has been analyzed in curarized guinea pigs. Round window recordings demonstrated that conditioning electrical stimulus trains delivered to the cerebellar cortex diminished the CM and AP amplitude at the same time and in a parallel fashion. On the other hand, cooling of the cerebellar cortex showed the opposite results of increased amplitudes. All pre-receptorial mechanisms were avoided. A PDP-12 computer performed parametric and non-parametric statistical analysis showing the differences to be significant for the shifts. Evidence of simultaneous inhibitory cerebellar action on both potentials has been demonstrated and a cerebello-olivo-cochlear pathway is proposed for such action upon the receptor cells and/or incoming fibers.


Hypothermia produced by peripheral and central injections of chlorpromazine in aged rabbits.

Hypothermia produced by IV administration of chlorpromazine (CPZ, 0.5-2.0 mg/kg) in a thermoneutral environment was greater in rabbits 2-4.5 years old than in animals under 24 months of age. One microgram CPZ given intracerebroventricularly (ICV) produced greater hypothermia in the older animals in tests performed in a thermoneutral environment while 0.25 and 0.5 microgram doses did not. The hypothermogenic effect of all three ICV doses of CPZ was enhanced in older rabbits exposed to cold. The brain of the older rabbit appears to be more sensitive to the hypothermogenic effects of CPZ. The findings suggest that this widely used tranquilizer can contribute to accidental hypothermia of the aged.


Intracellularly studied excitability changes in coronal-pericruciate neurons following low frequency stimulation of the corticobulbar tract.

Direct intracellular measurements of excitability changes to injected current were made in 116 cortical neurons of awake cats following antidromic or orthodromic activation by repetitive, 1-6 Hz stimulation of the pes pedunculi. The predominant effect seen in antidromically activated cells was a transient decrease in excitability and input resistance. The predominant effect seen in orthodromically (transsynaptically) activated cells was a transient increase in excitability and input resistance. In the absence of accompanying change in rates of spontaneous spike activity, the above results suggest that adaptations supporting the changes in excitability and resistance occur locally to these cells.


Effects of damage to median raphe nucleus on ingestive behavior and wheel running activity.

The effects of damage to the median raphe nucleus on the ingestive behavior and wheel running activity of rats were studied. This nucleus was damaged by the placement of either electrolytic or chemical (5,7-dihydroxytryptamine) lesions. After the placement of either type of lesion, wheel running activity was significantly decreased for the duration of the 8 week post-operative period. Although there were transient decreases in both food and water intakes after damage to the median raphe nucleus, these decreases did not appear to result from impairments in neuro-regulatory mechanisms. Rather, the decrease in food intake seemed to be related to the decrease in locomotor activity, and the decrease in water intake appeared to be linked to the decrease in food intake. In some rats with electrolytic lesions in the median raphe nucleus, the decrease in water intake was followed by a transient period of hyperdipsia.


Depression of spontaneous and ionophore-induced transmitter release by ruthenium red at the neuromuscular junction.

The effects on spontaneous and ionophore-induced transmitter release of the inorganic dye, ruthenium red (RuR), a known inhibitor of calcium binding sites, were observed at the frog sartorius neuromuscular junction using intracellular recording techniques. Both crude and purified RuR, at concentrations of 1 and 5 micron depressed or blocked spontaneous release of acetylcholine (ACh) and reduced postsynaptic sensitivity to ACh, the crude dye being more potent than the pure. Pretreatment of muscles with RuR prevented the catastrophic reaction of junctions to 100 micron X537A ionophore. Increased levels of Ca2+ restored spontaneous transmitter release to control levels after depression or blockade by RuR. It was concluded that RuR blocks a critical membrane-bound binding site for calcium which is necessary for quantal release of transmitter.


Ventilation and chemoreflexes during enflurane sedation and anaesthesia in man.

Enflurane sedation and anaesthesia in healthy fit subjects reduced ventilation and the response to carbon dioxide, hypoxaemia and a low dose of doxapram, all in a dose-related fashion. Comparing the three chemoreflexes tested, the response to hypoxaemia and doxapram were the more profoundly impaired; they were nearly totally abolished by anaesthesia. These effects of enflurane on chemoreflex activities are qualitatively similar to those previously observed with halothane.


Impairments in saline intake induced by deposit-free electrolytic lesions in the thalamic gustatory area.

Previous studies demonstrating impairments in sodium appetite following destruction of the thalamic gustatory relay of the rat utilized lesion procedures which depositd irritative ferric ions around the lesion site. The present study used a deposit free lesioning procedure to determine whether the disruption in sodium appetite is attributable to factors other than tissue destruction. The results showed that deposite free lesions produce deficits in sodium appetite which are similar in specificity, intensity, and uniformity to those produced by irritative lesion procedures.


Coaxial scavenger for paediatric anaesthesia.

A new scavenging device suitable for the Jackson-Rees modification to the Ayre's T-piece is described. This device maintains the essential components of the modification while effectively scavenging the circuit.


Reduction of nitrous oxide contamination in a paediatric hospital.

Ambient nitrous oxide concentrations were recorded in an operating room during delivery of the gas at low and medium flow-rates, with and without the application of simple scavenging devices. Residual background levels of nitrous oxide were still present more than one hour after disconnection of the flowmeters and use of the room. Scavenging reduced concentrations ten-fold. Adjacent corridors and the post-anaesthetic recovery room were contaminated with nitrous oxide from the operating rooms and from patients. A vigorous programme of checking for leaks and repairing and maintaining equipment, coupled with the use of suction scavenging, can reduce atmospheric contamination with nitrous oxide below 30 p.p.m., which is well within the limit suggested by the U.S. National Institute for Occupational Safety and Health.


[Blood and urinary cyanide concentrations during long-term sodium nitroprusside perfusion].

Five deeply comatose neurological patients were administered a continuous perfusion of sodium nitroprusside (SNP) at the rate of 3 microgram.kg-1.min-1. The levels of blood cyanide (CN-) were measured two hours after the start, then every 12 hours during, and 12 and 24 hours after the end of perfusion. The urinary output of CN- was also studied. The results show that total blood CN- stabilized after 36 hours to a mean value of 0.11 mg/l. When perfusion was stopped, CN- blood levels dropped but did not reach pre-perfusion values at the 24th hour. Urinary excretion of CN- which reached a maximum value of 0.050 mg/24 h represents a negligible amount and does not explain the fall of blood CN- and the occurrence of a concentration plateau. The results showing lower values obtained on non-anesthetized patients during the first hours of perfusion compared to those of a previous study done under neuroleptanaesthesia are discussed. These results suggest that prolonged perfusions at SNP at the rate of 0.177 mg.kg-1.h-1 do not produce toxic blood level of CN-.


Epidural analgesia and the metabolic response to surgery.

The effect of epidural blockade on the metabolic and hormonal responses to pelvic surgery was investigated in 14 female patients. Central venous blood samples were collected every 30 minutes and analysed for free fatty acids, glycerol, beta-hydroxybutyrate, acetoacetate, glucose, lactate, pyruvate, cortisol and growth hormone concentrations. There was no change in fat and glucose metabolism except for a transient decrease in lipolysis after 30 minutes of surgery. Cortisol and growth hormone values were significantly increased (p less than 0.01) after 60 minutes. A small but statistically significant increase in blood lactate concentration was observed (p less than 0.01) and the concept of a "metabolic V/Q" abnormality is postulated to explain the lacticacidaemia.


A comparison of the effects of continuous ketamine infusion and halothane on oxygenation during one-lung anaesthesia in dogs.

It has been shown that a continuous infusion of ketamine during one-lung anaesthesia combined with a 50 per cent oxygen-curare anaesthetic technique will provide consistently lower shunt fraction and higher Pao2 compared with halothane under the same experimental conditions. Because no additional factor was observed which could account for these changes and because the responses of the animals to the two anaesthetic agents were similar--the only difference being a different initial set point--the experimental model may be considered adequate. In the authors' view the difference in shunt fractions may be attributed to a more stable hypoxic reflex during ketamine anaesthesia. Further experimentation will be necessary to fully exclude the possibility of sequence-related changes affecting some of these results and to determine whether or not certain groups of dogs respond in a qualitatively different fashion.


Can naloxone inhibit the cardiovascular effect of acupuncture?

Forty dogs were studied during MAC-1 halothane anesthesia with a chronically implanted electromagnetic flow probe on the ascending aorta. Cardiac output, stroke volume, heart rate, mean arterial pressure, pulse pressure, central venous pressure and total peripheral resistance were determined in addition to Pao2, pH, Paco2 and base deficit. Acupuncture moxibustion with electrocautery at Jen Chung (Go-26) produced a significant (five per cent level) increase in the cardiac output, stroke volume, heart rate, mean arterial pressure and pulse pressure and a significant decrease in total peripheral resistance during a 120-minute period of observation in dogs under halothane anaesthesia. Acupuncture moxibustion at Go-26 following pretreatment with the narcotic antagonist naloxone (1 mg.kg-1) produced a significant increase in cardiac output, heart rate, mean arterial pressure. It is concluded that naloxone, which inhibits the analgesic effects of acupuncture, does not inhibit the symphathomimetic effect of acupuncture or moxibustion at Jen Chung (Go-26) in dogs under light MAC-1 halothane anaesthesia.


Ventricular fibrillation in a patient with unsuspected mitral valve prolapse and a prolonged Q-T interval.

Mitral valve prolapse is a common cardiac abnormality associated with arrhythmias and sudden death. In most instances it can be diagnosed on the basis of physical findings. Those patients who are symptomatic or who display electrocardiographic abnormalities appear to be most susceptible to arrhythmias and, therefore, may be at increased risk for anaesthesia. Because the syndrome is relatively common and may present a very innocent clinical picture, anaesthetists should be aware of this condition and the problems it may present. A case of mitral valve prolapse syndrome associated with ventricular fibrillation on induction of anaesthesia is reported. The symptoms and pathophysiology of the disorder are reviewed and the potential problems and the anaesthetic management are discussed.


Anaphylactoid reaction to mannitol.

A 16-year old boy with a lesion of the right eye developed, during the preoperative administration of a mannitol infusion, an anaphylactoid reaction characterized by hypotension, periorbital oedema and bronchospasm. This quickly resolved following cessation of the infusion and appropriate therapeutic measures. There were no long-lasting effects. We considered mannitol the causative agent because of its temporal relationship to the reaction and our inability to seriously implicate any other medication. A history of childhood atopy may have been a predisposing factor.


Unilateral pulmonary oedema: a case report.

We have presented a case of unilateral pulmonary oedema which we feel is secondary to obstruction of the right main bronchus during spontaneous respiration. An anode tracheal tube was introduced through a tracheostomy during operation in a man with pre-existing pulmonary and cardiac disease. At the end of the anaesthetic, acute obstruction to ventilation of the right main bronchus developed with the tube still in place and the patient breathing spontaneously. The obstruction was relieved, by repositioning of the tracheal tube, but not before the patient developed right unilateral pulmonary oedema.


The effect of wheat germ agglutinin on sialyl and galactosyltransferases of rat liver Golgi membranes.

The sialyltransferase and galactosyltransferase activities of the Golgi-rich fraction from rat liver were enhanced by the binding of wheat germ agglutinin (WGA). The sialytransferase was more sensitive than the galactosyltransferase to the WGA. Maximal stimulation of the galactosyltransferase activity resulted from the binding of 60--80 micrograms WGA to the Golgi membrane, while only 40 micrograms of WGA produced a maximal enhancement in the sialyltransferase activity. Within 5 min of WGA binding, the Golgi sialytransferase activity was doubled. After the initial binding of WGA to the Golgi fraction, the galactosyltransferase activity was decreased by 30%. However, in 15 min the activity was doubled by the binding of WGA. The activities of both enzymes were further enhanced by incubation for up to 90 min. The stimulation of both sialyltransferase and galactosyltransferase activities by WGA was reversed by N-acetyl-D-glucosamine (GlcNAc), the specific inhibitor of agglutination by WGA. Complete reversal of the enhanced activity was observed after 20--30 min in the presence of 1 micromol GlcNAc. The association constant for the binding of WGA to the Golgi membranes was calculated to be 4.16 X 10(-6) M from a Steck-Wallach plot. The 'n' value or mean binding sites was calculated as 5.26 X 10(-5) M/mg of Golgi membrane protein.


Proteolytic conversion of rat thymus DNA polymerase alpha to a more active form.

The relationship between two DNA polymerase alpha species from mammalian tissues has been resolved with the isolation of a protease from rat thymus which converts the larger alpha polymerase (7.3S) to a smaller (5.4S) size. The proteolytic activity is present only in the chromatin fraction and the limited proteolysis is accompanied by an increase in activity of the DNA polymerase, possibly consistent with a biological control function for this phenomenon.


Cell-free synthesis of rat liver zinc-thioneins.

The induction of rat liver zinc-thioneins mRNA was studied in a wheat germ cell-free translation system. Liver poly A rich polysomal RNA was isolated from rats which had been injected with zinc sulfate 5 h previously. These RNA preparations stimulated the incorporation of [35S]cystine into trichloroacetic acid insoluble proteins when assayed in the cell-free synthetic system. The translation products were characterized by Sephadex G-75 chromatography in 8 M urea--50 mM beta-mercaptoethanol, by disc gel electrophoresis in 4 M area--Tris-glycine buffer (pH 9.2), and by peptide fingerprinting with pepsin. These results were identical with authentic rat liver zinc-thioneins. The zinc-thioneins mRNA activity in the control rats, however, was minimal. The stimulation in zinc-thioneins synthesis observed in the cell-free synthesis was similar to the increased synthesis of these polypeptides in vivo.


Interaction of spironolactone with rat skin androgen receptor.

Some characteristics of the dorsal skin cytoplasmic androgen receptor (AR) have been studied in male rats. The affinity constant, the binding specificity, and the sedimentation profile of the receptor have been found to be similar to the rat prostate AR. The measurement of the number of binding sites in various hormonal conditions (deprivation) led to the conclusion that this receptor was largely occupied by endogeneous hormones from gonadal and (or) adrenal sources. Administration of spironolactone or canrenone to 7-day-castrated rats was accompanied by a rapid and drastic decrease of available binding sites. This diminution was ascribed to the competitive inhibition of canrenone, the active in vivo metabolite of spironolactone. It is postulated that the antiandrogenic action of spironolactone, at the skin level, is mediated by canrenone which inhibits the formation of specific testosterone and (or) 5 alpha-dihydrotestosterone receptor complex in cytoplasm and consequently in nuclei.


Affinity chromatography of Ruta graveolens L. O-methyltransferases. Studies demonstrating the potential of the technique in the mechanistic investigation of O-methyltransferases.

Two discrete furanocoumarin (5- and 8-)O-methyltransferases and a caffeic acid 3-O-methyl-transferase from cell cultures of Ruta graveoleus L. have been copurified by affinity chromatography on 1,6-diaminohexane agarose (AH-Sepharose 4B) linked with S-adenosyl-L-homocysteine (SAH). The furanocoumarin O-methyltransferases, which transfer a methyl group from S-adenosyl-L-methionine (SAM) to the 5- or 8-hydroxyls of linear furanocoumarins, were not retarded by 5-(3-carboxypropanamido)-xanthotoxin (CPAX) immobilized to AH-Sepharose 4B, but addition of SAM to the irrigant buffer led to complete retardation of both enzymes on this affinity system. An analogous phenomenon was observed for the caffeic acid O-methyltransferase, with a ferulic acid ligand coupled to the same insoluble support. SAH was as effective as SAM in promoting binding of the furanocoumarin O-methyltransferases to CPAX and caffeic acid 3-O-methyltransferase to immobilized ferulic acid, respectively. The strong and specific adsorption of these enzymes was abolished by exclusion of SAM or SAH from the irrigant buffer. It is concluded that the enzymes bind first to SAM or SAH, and that this binding process in turn induces the binding site for their specific phenolic substrates or their analogs. Based on these findings, a compulsory-ordered kinetic mechanism for the action of these O-methyltransferases is postulated.


Mycotoxins in animal feedstuffs in Ontario: 1972 to 1977.

Records of the Toxicology Laboratory, Veterinary Services Branch, Ontario Ministry of Agriculture and Food, indicate that 277 of 2,022 specimens of feedstuffs submitted between October 1, 1972 and September 30, 1978 contained one or more mycotoxins. The data indicate that zearalenone is an important mycotoxin in the provincial corn crops and that its incidence fluctuates from year to year. The percentages of specimens containing zearalenone were 16.3 (1972), 4.1 (1973), 5.5 (1974), 22.4 (1975), 9.5 (1976) and 13.0 (1977). Aflatoxins, ochratoxins and T-2 toxin were found in some specimens but their incidence was low.


Experimental bovine pneumonic pasteurellosis. I. Prevention of the disease.

Fifteen three- to six-month old Hereford-cross calves were divided into three groups. The first group was inoculated with bovid herpersvirus 1 (Strain 108), the second with a commercial intranasal vaccine against bovid herpesvirus 1 and the third group acted as controls. At least three weeks after vaccination, all calves were weaned, placed in an environmental chamber at 25.0 degrees C (days) and -13.3 degrees C (nights) and challenged with an aerosol of bovid herpesvirus 1 followed four days later by an aerosol of Pasteurella haemolytica. All surviving calves were sacrificed four days after the second aerosol. None of the calves inoculated with bovid herpesvirus 1 virus or the commercial vaccine developed a generalized pneumonia, although there were one or two nodules (4--8 mm diameter) in two of the calves given the commercial vaccine. Four of the five control calves had extensive lobar pneumonia at necropsy, two of the five died from the disease. Details of the clinical, pathological, bacteriological, virological and some of the serological findings are reported.


Experimental bovine pneumonic pasteurellosis. II. Genesis and prevention.

Two experiments were conducted. In the first, 16 crossbred Hereford calves were divided into two equal groups. The first group was vaccinated intranasally with a commercial vaccine against bovid herpesvirus 1 and the second group was unvaccinated. The calves were later exposed to an aerosol of bovid herpesvirus 1 (strain 108) for five minutes. Four calves from each group were subjected to transportation and four calves from each group were kept in an environmental chamber for four days. Four days after viral aerosol all calves were exposed to an aerosol of Pasteurella haemolytica and the same subgroups were again transported or held in the chamber for a further four days. The calves that did not die from pneumonia were necropsied ten days after the final day of transport. Pulmonary lesions were present in both vaccinated and control animals but were less extensive in the vaccinated calves. Six of eight vaccinated but none of the eight control calves survived. In the second experiment, eight crossbred Hereford calves were divided into two equal groups. One group was vaccinated with bovid herpesvirus 1 (strain 108) and the other acted as controls. Four weeks later all calves were sequentially exposed to aerosols of bovid herpesvirus 1 (strain 108) and P. haemolytica four days apart. Three of the four controls but none of the vaccinates died from pneumonia. Every lobe of the lungs in all the controls was affected by pneumonia while no pulmonary lesions were found in the vaccinated calves. The differences in efficacy of the modes of vaccination and the possible role of transport stress are discussed.


Bovine and equine onchocerciasis in eastern North America with a discussion on cuticular morphology of Onchocerca spp. in cattle.

Skin sections and/or the ligamentum nuchae and ligamentum gastrolienale were examined from twelve bovine carcasses obtained from southern and eastern Ontario and from Quebec. Of these, seven were shown to be infected with Onchocerca gutturosa and/or Onchocerca lienalis. The morphology of the adult female cuticle is discussed. Skin sections from 43 equine carcasses from a slaughter house in Grenville, Quebec were examined and microfilariae of Onchocerca sp. were recovered from 32 (74%). There are probably referable to Onchocerca cervicalis.


A syndrome of hereditary tyrosinemia in mink (Mustela vison Schreb.).

A hereditary disease in mink (Mustela vison Schreb.) leading to death when the affected kits are about six weeks old has been investigated. The disorder is inherited as a simple autosomal recessive character. Strongly elevated plasma tyrosine concentration is an outstanding feature of the disease. An enzyme defect in tyrosine aminotransferase (EC 2.6.1.5) or 4-hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27) is considered together with the possibility of a parallel between the disease in mink and the disease tyrosinosis or hereditary tyrosinemia in man.


Probstmayria vivipara pinworms in ponies.

From 1967--1978 observations were made on the presence of the small equine pinworm, Probstmayria vivipara, in seven experimental ponies. The life cycle of this nematode is unusual in that it is endogenous with development of all stages occurring within the host's digestive tract. Initially, worms were found in the feces of four of seven ponies following treatment with thiabendazole but the infection was later transmitted to all ponies possibly via coprophagy. Still later, based on fecal and postmortem examinations, four of the seven ponies lost their pinworm burdens. At necropsy, the principal sites of infection were observed to be the cecum and right ventral colon. Despite the large number of pinworms present, clinical signs were not observed.


Acquired retinal macroaneurysms.

Five patients with retinal macroaneurysms are described. The aneurysms may be an incidental finding or they may cause visual loss from retinal, preretinal and vitreous hemorrhages or from macular edema or exudation. The prognosis is good in those cases presenting with hemorrhage but is poorer in those with macular problems. Acquired aneurysms are found in older patients who are hypertensive or have vascular disease. We believe that retinal emboli play an important part in their development.


How do tears drain? Technetium studies.

We examined the tear drainage system of twenty-fiv normal volunteers by scintillography with Technetium Tc 99m (Pertechnetate). We photographed the changes occurring in the lacrimal sac and nasolacrimal duct during closure and opening of the eyelids. Our findings support Jones' views of normal tear drainage. The tracer was concentrated in the lacrimal sac while the lids were closed for 3 minutes and descended into the nasolacrimal duct as soon as they opened.


The water provocative test in preglaucomatous chickens.

Our ability to induce glaucoma in birds provides an experimental system for exploring the mechanisms involved in the provocative water test. Waters loads of a level comparable to those used clinically produced larger intraocular pressure (IOP) changes in preglaucomatous and glaucomatous birds than in control birds. The magnitude of the response corresponded to the level of IOP before testing, that is, to the severity of the glaucoma. Changes in systemic blood pressure were not involved in the response. While hyotonicity of plasma may be the systemic determinant, the normal range of variation in this factor does not allow us at present to consider this a causal relationship.


Does a barbiturate drug given in lethal dose enter the cornea?

We wished to see whether sodium phenobarbital (one of the commonest drugs used to commit suicide) given in a lethal dose would enter the cornea. Guinea pigs and rabbits were killed with an overdose of the drug. Using gas chromatography we were able to detect the drug not only in the vascular ocular tissues and the intraocular fluids but also in the avascular tissues such as the cornea.


The anticomplementary activity of the rabbit lens.

We wished to determine if inhibitors of the complement system are present in the normal rabbit lens. Soluble less extract in various dilutions was incubated with normal human serum (as source of complement). The residual hemolytic activity was measured using sheep erythrocytes sensitized with antisheep rabbit hemolysin. The lens extract was found to contain two heat stable anticomplementary factors of different molecular weights capable of cleaving C2 and C4. Gel filtration showed that one of these factors was located in the alpha-crystalline region. It is suggested that the anticomplementary factors in the lens may be related to a natural mechanism for the modulation of complement mediated lens injury.


Falciform fold of retina.

A boy of 2 had evidence of congenital retinal non-attachment. The mother had a veil like fold in one eye. There was no evidence of any systemic disorder. The inheritance might be X-linked recessive. Mild manifestations of the disease in the carrier mother may be more frequent than has been assumed and should be looked for.


The physician, the university and the community.

A physician is one who practises the healing art, including medicine and surgery -- is that enough?  The university is an institution for the promotion of education in the higher branches of learning -- is that enough?  The community, which requires both and supports both, has shown signs of discontent which we must appraise and appreciate. Ophthalmology, which has often led the way in the past in scientific endeavour, now has an opportunity to lead again, into areas of need in the community.


[Timolol maleate. Pharmacology and review of the literature].

The sympathetic system is composed of alpha and beta receptors. Beta blockers block the beta effect competitively. They slow the heart and decrease its contractile strength. They block bronchodilatation and the vasodillation of muscular arteries. Timolol is a non specific beta blocker. It decreases intraocular pressure by reducing aqueous humor formation. It does not change outflow facility. Its action starts twenty minutes after a topical drop, is maximum two to four hours later and lasts 24 hours and more. Timolol o.50% seems equivalent to pilocarpine 4% while Timolol 0.25% seems equivalent to epinephrine 2%. There is a further drop in pressure when added to pilocarpine, diamox as maximum medical treatment. Tables show its advantages, drawback, adverse reactions, and precautions to be taken.


Effect of testosterone and 6-hydroxydopamine treatment on the metabolism of catecholamine and 5-hydroxytryptamine in methylcholanthrene-induced prostate carcinoma of rats.

The precursors tyrosine and tryptophan as well as the synthesizing and deaminating enzymes of catecholamines have been identified in methylcholanthrene-induced prostatic carcinoma of rats. Tyrosine hydroxylase, monoamine oxidase, catechol O-methyltransferase, dopamine, 5-hydroxytryptamine, and 5-hydroxyindoleacetic acid seemed to be neoplastic in origin, since electron microscopic studies failed to reveal the presence of any neuronal elements in this squamous epithelial cell carcinoma. Castration of rats significantly reduced the activity of tyrosine hydroxylase and the levels of tyrosine, dopamine, tryptophan, 5-hydroxytryptamine, and 5-hydroxyindoleacetic acid in prostate tumors. The changes appeared to be androgen specific since reintroduction of testosterone restored several of these biochemical parameters virtually to control limits. Chemical sympathectomy induced by 6-hydroxydopamine failed to alter monoamine metabolism; however, the prostatic tumor grown in 6-hydroxydopamine-treated rats showed significantly (32%) less necrosis than those grown in normal animals.


Vagal inhibitory effects on peripheral circulation in acute coronary occlusion.

The reflex adjustments of the peripheral circulation in response to acute coronary occlusion were studied in anesthetized dogs with isolated vascular beds perfused at constant flow. Coronary occlusion caused significant increases in perfusion pressure which averaged 27 +/- 4 mmHg in the hindlimb, 19 +/- 8 mmHg in skeletal muscle, and 13 + 5 mmHg in the mesenteric artery. These responses were less than half those caused by a similar decrease in aortic pressure obtained with hemorrhage. Coronary occlusion caused no significant changes in renal and paw circulations, while marked vasoconstriction resulted from hemorrhage. When aortic pressure was maintained constant throughout the duration of coronary occlusion, there was a significant vasodilatation in all beds studied. After vagotomy, coronary occlusion caused a constrictor response similar in magnitude to that caused by hemorrhage in each vascular bed and the dilator responses to occlusion at constant aortic pressure were abolished. Both constrictor and dilator changes were prevented by alpha-adrenergic blockade. Mechanical distension of the left ventricle in four dogs with carotid sinus nerves cut caused a significant reflexdilatation in the hindlimb. Thus, coronary occlusion initiates an inhibitory reflex mediated by vagal afferents which opposes peripheral vasoconstriction most effectively in the renal and paw circulations.


Teratogenic effects of diazepam in the hamster.

Pregnant hamsters were treated with different doses of oral and intravenous diazepam during the period of organogenesis. Teratogenic effects of diazepam were observed following oral treatment on days 8 and 10 and following intravenous treatment on day 11 of gestation. Types of malformations included cleft palate, exencephaly, limb anomalies, and hemorrhage. A dose-effect relationship was not observed. Comparison with reported literature seems to indicate that diazepam may be a mild teratogen in some species.


Structure-activity studies of [des-Arg9]-bradykinin on the B1 receptor of the rabbit aorta.

Eight L-alanine analogues of [des-Arg9]-bradykinin and a few other compounds substituted in positions 5 and (or) 8 have been tested on rabbit aortic strips in order to identify the group(s) responsible for binding and (or) stimulation of the B1 receptor. The results obtained with the L-Ala series have shown that the active group is located at the C-terminal end and it is probably Phe8, while the middle part and the N-terminal end of the peptide molecule are primarily involved in binding the agonist to the receptor. An aromatic ring is required in position 8 for activation of receptors, since the elimination or aromaticity (as in [Leu8,des-Arg9]-bradykinin and in [cyclohexylalanine8,des-Arg9]-bradykinin) brings about pure and competitive antagonists. Some compounds exert an angiotensin-like effect when applied at very high concentrations.


Effect of isoproterenol on phosphorylase activation in the hyperthyroid rat heart.

Pretreatment of rats for 3 days with triiodothyronine produced an increase in rate in the right atrium and a decrease in force of contraction in the right ventricle and Langendorff heart. Isoproterenol administration produced a time-dependent increase in rate and tension. The increase in rate was consistently greater in atria from hyperthyroid rats, and the increase in tension consistently greater in tissues from euthyroid rats. Isoproterenol also produced a time- and dose-dependent increase in phosphorylase a activity. In the isolated atria and ventricles enzyme activity was similar in the two groups. In the Langendorff hearts, however, there was an enhancement of the isoproterenol-induced increase in phosphorylase activity in hearts from hyperthyroid rats. Reduction of the coronary blood flow to the level found in euthyroid animals did not reduce the potentiation of phosphorylase activation found in hearts from hyperthyroid rats. It is concluded that the potentiation of phosphorylase activation in hearts from hyperthyroid rats is not due to the increase in coronary blood flow.


Electrical coupling in the circular muscles of dog jejunum.

Two distinct layers of circular muscle have previously been demonstrated in dog jejunum, the main circular layer containing many gap junction contacts, and an inner dense muscle layer where no gap junctions have been found. Length constants were determined for these muscle layers and no significant difference was found between these values. The main circular muscle cells had lower membrane potentials and may have had abnormally low space constants owing to injury. It was concluded that the absence of gap junctions in the inner dense layer does not reduce the spread of passive current as might be expected of electrically isolated cells, and it is suggested that an alternate pathway for passive current exists in this layer.


High-affinity choline uptake in regions of rat brain and the effect of antidepressants.

The effect of tricyclic antidepressants, chlorpromazine, and some monoamine oxidase inhibitors on the accumulation of [14C]choline by crude synaptosomal (P2) fraction from different regions of rat brain (cortex, striatum, and hippocampus) was investigated. Analysis of choline uptake kinetics resulted in high- and low-affinity components with different Michaelis constants. All tricyclic antidepressants tested inhibited in a dose-dependent manner the high-affinity choline uptake in the three regions, amitriptyline being the most potent. The IC50 values correlated significantly with the relative potencies of imipramine congeners in binding to muscarinic receptors in the brain. Neither tranylcypromine nor pargyline in concentrations up to 0.1 mM had any effect on choline transport. Concentrations of tricyclic antidepressants effective in inhibiting the uptake of choline failed to influence significantly the activity of choline acetyltransferase in brain regions examined. The results suggest that the effect of imipramine congeners on high-affinity choline uptake may be reflected in the anticholinergic properties of these compounds.


Central antihypertensive properties of muscimol and related gamma-aminobutyric acid agonists and the interaction of muscimol with baroreceptor reflexes.

The central antihypertensive properties of four gamma-aminobutyric acid (GABA) analogs were characterized in anesthetized cats with implanted intracerebroventricular cannulae. An intracerebroventricular infusion (icv) of muscimol, 0.1--0.5 microgram/min (total dose: 1--5 micrograms, icv), substantially reduced mean arterial pressure and slightly reduced heart rate. The compound was not hypotensive at 5 micrograms, iv (total dose) and only slightly hypotensive after an intracisternal injection (5 micrograms). Kojic amine (2-aminomethyl-5-hydroxy-4H-pyran-4-one) and baclofen were also hypotensive following an intracerebroventricular infusion, but they were less active than muscimol. GABA, at 15--150 micrograms/min, icv (total dose, 150--1500 micrograms, icv), was not hypotensive by itself and unlike muscimol its activity was not enhanced in cats pretreated with nipecotic acid, an uptake inhibitor of GABA. The ability of muscimol to interfere with baroreceptor reflexes was considered in experiments in which reflex vasoconstrictor (carotid occlusion) and reflex vasodilatation (acute elevation in mean arterial pressure with norepinephrine) was measured in the perfused hindlimb of cats previously prepared with intracerebroventricular cannulae. Muscimol significantly attenuated the response to bilateral carotid occlusion and completely abolished reflex vasodilatation. The results suggest that GABA agonists and analogs may regulate blood pressure centrally and, through an interaction with the central nervous system, may attenuate baroreceptor reflexes.


Alterations in ventilation and gas exchange during exercise-induced carbohydrate depletion.

The relationship between ventilation (VE), oxygen consumption (VO2), and carbon dioxide production (VCO2) during work were studied in four trained males during exercise-induced carbohydrate depletion. Repeated bouts of heavy treadmill exercise (6 min at 95% VO2 max) were performed once per hour for 24 h in order to promote a shift in energy substrate from carbohydrate to fat. Measurements of VO2 and VCO2 recorded during each minute indicated that VO2 was unaffected by the number of runs, whereas VCO2 showed a progressive reduction which amounted to 24% during the final run. A corresponding decline of 19% was observed in the respiratory exchange ratio. No significant change in VE occurred between any of the runs. It is concluded that during heavy, repeated, muscular exercise, reductions in VO2, strongly suggestive of an increased fat oxidation, are not accompanied by a corresponding change in ventilation.


The effect of spironolactone on the arterial water, cation, and norepinephrine contents of control and 'one-kidney-one-clip' hypertensive dogs.

Spironolactone at 10 mg per kilogram per day was given to control and 'one-kidney-one-clip' hypertensive dogs for 6--7 weeks. Compared with untreated animals the treated animals had a lower arterial water content, a higher arterial, myocardial, and skeletal muscle sodium content, and variable changes in tissue potassium concentrations.


The effect of propranolol and dimethylpropranolol on cardiac conduction.

Isolated dog hearts perfused with blood from a donor dogand driven at two heart rates were used to compare the effects of propranolol with those of its quaternary ammonium derivative on atrial, atrioventricular (AV) nodal, and His-Purkinje conduction. Propranolol slowed only AV-nodal conduction, increasing the minimal conduction time and the effect of prematurity, without affecting fatigue. Practolol did not have this effect. Dimethylpropranolol had similar but not identical effects on the AV node, but also slowed atrial and ventricular conduction. In contrast with the quaternary derivative of lidocaine, dimethylpropranolol's effect on atrial and ventricular conduction was not dependent on the heart rate. The effect of dimethylpropranolol on ventricular conduction was observed at doses lower than those reported by others to be antiarrhythmic.


Action of narcotic analgesics and antagonists on spinal units responding to natural stimulation in the cat.

Morphine and morphine-related agents were applied by microiontophoresis in the lumbar spinal cord of spinal cats to single units classified on the basis of their responses to natural cutaneous or proprioceptive stimulation. Opiate application had a current-dependent depressant effect on the ongoing activities of about one-third of the units tested. This effect was observed in laminae I and IV--VI, but only with units responding to noxious cutaneous stimuli: the nociceptive responses were themselves depressed. Excitatory and inhibitory responses to glutamate and gamma-aminobutyric acid, respectively, were also depressed. Intravenous administration of the opiates at doses reported to produce analgesia in the cat also depressed only units responding to noxious cutaneous stimuli, including their nociceptive responses. This depression could be reversed by either the iontophoretic application (100 nA) or the intravenous administration (0.1--0.8 mg/kg) of naloxone. These results are interpreted as further evidence that the analgesic effects of opiates are at least partly due to an action at the spinal level.


A novel method to separate the layers of the intestine.

By applying cellulose acetate paper to the lumenal and serosal surface of the intestine of rats, we have divided the intestine into three layers. Examining the layers histologically, we have shown that most of the villi are removed from the mucosal surface, ther serosa alone is removed from the serosal surface, and muscle layers. This appears to provide a rapid procedure for separation of the layers of the intestine for histological and biochemical studies.


Carotid sinus reflex and norepinephrine release following acute volume depletion in dogs.

Norepinephrine (NE) release and pressor response to sympathetic stimulation were studied in dogs under furosemide-induced acute volume depletion. The rise in blood pressure observed following carotid clamping proved similar before and after acute salt and water depletion in the first group of animals and NE rose comparably in these two conditions. Similar results were obtained in a second group of dogs that received an angiotensin II converting enzyme inhibitor (CEI). This study shows that contrary to isotonic saline loading, acute salt and water depletion cause a progressive increase in NE plasma levels. Moreover, these results clearly demonstrate that the decrease in sympatho--adrenergic response and the predominant role played by the renin--aniotensin system during chronic salt depletion are not observed in acute conditions.


Defect in regulation of membrane transport of monosaccharides in dystrophic muscle.

The penetration of a nonmetabolized glucose analogue, 3--O-methyl-D-glucose, across the plasma membranes of tissues from dystrophic mice and cardiomyopathic (dystrophic) hamsters has been compared with that of normal controls. Under basal conditions the penetration of test sugar was similar in lens and diaphragm of normal and dystrophic 129/ReJ mice. Stimulation of sugar transport by 2,4-dinitrophenol did occur in normal but not in dystrophic diaphragm. A submaximal concentration of insulin had a more variable effect in dystrophic than in normal muscle while a supramaximal concentration of the hormone increased the uptake of the glucose analogue to an equal extent in the two tissues. In the BIO 14.6 strain of cardiomyopathic hamsters, uncoupling of oxidative phosphorylation did not increase sugar transport in extensor digitorum longus muscles, while the normal effect was observed in dystrophic soleus and in both these muscles of the random bred controls. The absence of an effect by a condition simulating anoxia suggests that in dystrophy, certain muscles are unable to accelerate the entry of glucose when this is required.


Bile flow and electrolyte composition of bile associated with maximum bilirubin excretion in sheep.

Changes in the composition of bile accompanying the maximum biliary excretion (Emax) of bilirubin were investigated in sheep. Sheep fitted with chronic 'T-tubes' in the common bile duct were infused with taurocholate and bilirubin at various rates. Bile collected during both pre- and post-bilirubin steady-state periods was analyzed for the biliary concentration of electrolytes, bile salts, and bilirubin. Bilirubin Emax was 24.6 mumol/min while bile salt excretion during this period was 103 mumol/min. At Emax bilirubin entry into bile reached a concentration of 16.1 mumol/mL, increased the biliary concentration of sodium, did not change osmolarity of bile, and did not increase bile flow. The data suggest that bilirubin either interacts with mixed micelles in bile or forms molecular aggregates.


Adrenergic presynaptic receptors: examination of a hypothesis in guinea pig vas deferens.

The hypothesis was examined that phenoxybenzamine enhances both the overflow of noradrenaline and the mechanical response in guinea pig vas deferens by blockade of presynaptic inhibitory receptors located on adrenergic nerve terminals which serve a negative-feedback function. Preparations were stimulated with a constant small number of pulses but at three different frequencies (1, 5, and 15 Hz) and the relative effectiveness of phenoxybenzamine in enhancing overflow assessed. According to the presynaptic receptor hypothesis inhibition of transmitter output should increase with increasing frequency due to increased activation of receptor sites by endogenously released noradrenaline. The antagonist enhanced the overflow of tritium but did so to a similar extent at all three frequencies, regardless of the length of the interval between pulses. Similarly, no evidence for a greater sensitization of the mechanical response by phenoxybenzamine at the higher frequencies was obtained. The conditions of the present experiment were considered optimal for the operation of the negative-feedback system and the results indicate that the physiological relevance of such a system is questionable.


Effects of noradrenaline and nicotinic acid on plasma free fatty acids and oxygen consumption in cold-adapted rats.

A 3-h noradrenaline (NA) infusion (1.5 microgram kg-1 min-1) produced a sustained enhanced oxygen consumption (O2 cons.) in cold-adapted rats. Plasma free fatty acid (FFA) levels were elevated by NA in control and in cold-adapted rats, but to lesser extent in cold-adapted rats; the increase was maintained at a plateau in both groups during the entire period of NA infusion. A 1-h nicotinic acid (Nic A) infusion (1.5 mg kg-1 min-1) added to the NA infusion inhibited the calorigenic response to NA in cold-adapted rats and reduced the elevated plasma FFA concentration in control and in cold-adapted rats to values below basal levels. However, when the Nic A infusion was stopped, the O2 cons. was increased again in cold-adapted rats by the uninterrupted NA infusion, without the simultaneous increase of the plasma FFA concentration; the plasma FFA concentration was maintained in cold-adapted rats below basal values and merely brought back to basal levels in control rats. From these results, it is suggested that plasma FFA are not an essential substrate to the calorigenic response to NA observed in cold-adapted rats, as 85% of the response can occur when the plasma FFA concentration is very low.


Effect of acute and chronic renal denervation on renal function after release of unilateral ureteral obstruction in the rat.

The role of the renal nerves in determining renal function after relief of 24-h unilateral ureteral obstruction (UUO) was studied using clearance techniques in anaesthetized rats. Acute renal denervation during the first 1--2 h after relief of UUO resulted in a significant increase in glomerular filtration rate (GFR), renal plasma flow (RPF), urine flow, and sodium and potassium excretion, changes which were not seen in the sham-denervated postobstructive kidney. Acute denervation of sham-operated normal kidneys caused a similar natriuresis and diuresis but with no change in GFR or RPF. Chronic renal denervation 4--5 days before UUO denervated postobstructive controls, while chronic denervation alone was associated with a significantly higher urine flow and sodium excretion rate from the denervated kidney. The effectiveness of renal denervation was confirmed by demonstrating marked depletion of tissue catecholamines in the denervated kidney. It was concluded that renal nerve activity plays a significant but not a major role in the functional changes present after relief of UUO. Chronic renal denervation did not protect against the functional effects of unilateral ureteral obstruction.


Simultaneous measurement of cell loss and gastric potential difference in the rat: effects of short-term fasting.

These experiments utilized ex vivo gastric chamber preparations in both fed rats and rats fasted for 14--18 h. A new, simple technique is described for the quantification of cells in small volumes of fluid. The data indicate that exposure to solutions of 50 mM HCl was accompanied by greater cell loss in fasted vs. fed animals. The gastric potential differences of mucosae exposed to Ringer's mammalian saline, and subsequently to 50 mM HCl, were consistently at least 10 mV more negative in fasted animals.


Acetylcholine does not stimulate the release of growth hormone from perifused rat adenohypophyses.

Acetylcholine (1 micromol/L--1 mmol/L) has been reported to stimulate growth hormone release from perifused bovine pituitary slices. We have carried out studies using the perifused pars distalis of the rat adenohypophysis to see whether a similar response is observed. Neither acetylcholine, acetylcholine with eserine, nor carbamylcholine, at concentrations of 10(-9), 10(-6), and 10(-3) M. stimulated the release of growth hormone. Thus we could not demonstrate a similar reponse to acetylcholine in the pars distalis of the rat adenohypophysis as reported in the bovine gland.


Uptake of liposome-entrapped mannitol by diaphragm.

Tissue uptake of liposome-entrapped radioactive mannitol was examined in rats and mice after both intravenous and intraperitoneal injection. In accord with results from other laboratories, liver and spleen effectively accumulated liposomes. Diaphragm also took up significant amounts of label. In nearly all cases the radioactive content of perfused tissues was less than tissues which were not perfused but this was statistically significant in only a few comparisons.


Isoniazid phenotyping of black as well as white patients.

The isoniazid phenotyping in black patients from Birmingham (Alabama) as well as from South Africa yielded a higher frequency of fast inactivation than that in the Canadian and U.S. white participants. Following an oral test dose of 10 mg isoniazid per kilogram, the incidence of fast acetylation was 58.7 and 60.3% in South African and Birmingham blacks, respectively. In the Canadian and Birmingham Caucasians the rate was 41.9 and 41.0%, respectively.


Antagonists of angiotensin II containing N-methyl-L-alanine and DL-nipecotic acid in position 7.

[1-sarcosine, 7-N-methyl-L-alanine, 8-isoleucine]-Angiotensin II and [1-sarcosine, 7-DL-nipecotic acid, 8-isoleucine]-angiotensin II were synthesized by the solid-phase method and purified by cation-exchange chromatography and high-pressure liquid chromatography. In the isolated rat uterus these analogs and less than 0.1% of the myotropic activity of angiotensin II and inhibited angiotensin II with pA2 values of 8.2 and 7.8, respectively. In the rat pressor assay (vagotomized ganglion blocked rat) these analogs had 0.9 and 2.8%, respectively, of the pressor activity of angiotensin II. The results show that the proline residue in position 7 of [Sar1,Ile8]-angiotensin II may be replaced by other secondary amino acids without disrupting interactions at angiotensin II receptors.


Correction factor for the estimation of plasma glucose synthesis from the transfer of 14C-atoms from labelled substrate in vivo: A preliminary report.

Based on a previously designed method for the estimation of the contribution of C-atoms by acetylcoenzyme A to the hepatic oxaloacetate pool, the loss of 14C-atoms on their way from a precursor to plasma glucose due to 'metabolic exchange' was estimated in normal and diabetic dogs and in normal rats. Due to this loss of 14C-atoms, the rates of gluconeogenesis when calculated from the transfer of 14C-atoms from precursors (other than glycerol) are underestimated by a factor of 2.2 +/- 0.07 in normal, 1.8 +/- 0.05 in diabetic dogs, and by 1.55 +/- 0.04 in normal rats.


Ecology and taxonomy of bacteria attaching to wood surfaces in a tropical harbor.

Water, sediment, and wooden pilings, samples of which were collected from a harbor in Puerto Rico during the course of a long-term study of biofouling of wood treated with creosote and related compounds, were found to support growth of microbial populations, the dominant taxa of which included Hyphomicrobium, Hyphomonas, Pseudomonas, Vibrio, and Bacillus. New wood exposed to the harbor water was rapidly colonized by Hyphomicrobium vulgare. Old pilings in an advanced stage of biodeterioration maintained a diverse bacterial microflora, representatives of which were also found widely distributed in the water column and sediment. Evidence for bacterial species succession was obtained, indicating that microbial interactions are important for attachment to, and subsequent colonization of, wood surfaces in the marine environment.


[Experimental study of vibrio parahaemolyticus (biotype 2) transfer from water and sediments to benthic marine food chain organisms].

Transfer of Vibrio parahaemolyticus (biotype 2) from sediments to water and from water to benthic marine organisms was studied experimentally using a streptomycin-resistant strain. Transmission by trophic pathways was also studied using reconstituted marine food chains (Mytilus edulis, Nereis diversicolor, Carcinus maenas, Scorpaena porcus, Mus musculus). Water colonization by sediments could be observed only at temperatures above 16 degrees C. Sediments could well constitute a disseminating reservoir for these germs, their cycle in water being dependent of the cycle followed in the sediments. Contamination of animal organisms is essentially effected by a direct mean, either water or sediments; transfer by trophic pathways being negligible. Infection of land consumers (mice) is linked quantitatively to the nature of the last marine organism of the food chain since bacteria can flourish in the digestive tract of certain animals (Carcinus maenas).


Trypsin-uncoupled synthesis and secretion of yeast invertase: implications for the mechanism of secretion.

The subcellular distribution of invertase was examined after synthesis and secretion by sphaeroplasts had been uncoupled by the addition of 30 microgram mL-1 trypsin. Sphaeroplasts secreted only the high molecular weight invertase during uncoupling by trypsin. The level of low molecular weight, 'small' invertase in the soluble internal pool was found to be elevated by over fivefold, and the membrane-associated pool was found to contain low molecular weight invertase in addition to intermediate molecular weight invertase, after 1.5 h of trypsin treatment. Purified plasma membranes from trypsin-treated sphaeroplasts had no detectable mannan synthetase activity. On the basis of these and previous findings, a working hypothesis wherein invertase is synthesized on the internal surface of the plasma membrane and glycosylated during its transit to the external surface is presented.


Aquarium pets as a source of antibiotic-resistant salmonellae.

Thirteen serotypes of Salmonella isolated from imported ornamental aquarium frogs, snails, and their waters were shown to be multi-drug-resistant. Among the resistances exhibited were resistance to gentamicin, sulfamethoxazole-trimethoprim, cephalothin, and nalidixic acid. Frog isolates displayed eight different patterns and snails isolates had two different resistance patterns. The most common serotype, Salmonella typhimurium, was resistant to 18 antibacterials while other salmonellae were resistant to 9 to 16 antibacterials. Resistances in S. typhimurium and S. bovis-morbificans were conjugative and a number of R plasmids participated in the resistance. The plasmid-mediated resistance in S. typhimurium was stable and the levels of resistance conferred were markedly higher than in the other salmonellae tested. Resistance of other serotypes was non-conjugative and resistance to the beta-lactam antibiotics was unstable.


Evidence for chemotaxis during sexual development in Dictyostelium discoideum.

Amoebae in mated cultures of Dictyostelium discoideum show oriented movement towards young aggregates, suggesting that cemotaxis is involved in macrocyst development. Amoebae also show directional movement towards midendocyte stages, indicating that as the macrocyst develops it continues to be a source of chemoattractant. These data are discussed in terms of our current knowledge about mating in the cellular slime moulds.


The effects of partial chronic denervation on forearm metabolism.

Effects of chronic denervation upon in vivo forearm metabolism were studied in six patients and six controls. The diagnosis was amyotrophic lateral sclerosis in four patients, the neuronal form of Charcot-Marie Tooth disease in one patient, and an unclassified chronic disease of the lower motor neurons in one patient. In all cases the forearm muscles showed clinical weakness and electrical evidence of denervation, while muscle biopsy from a proximal muscle of the upper limb showed typical denervation atrophy. At rest there was increased oxygen utilization and lactate output as well as a tendency for increased uptake of glucose and long chain fatty acids from arterial blood per 100 ml of forearm tissue. During exercise the abnormally high lactate output increased further. An increased arterial lactate concentration was present during rest and exercise. Oxidation of fatty acids was not impaired. It is suggested that these abnormalities are consistent with an augmented utilization of blood borne fuels at rest by denervated muscles. A concurrent regional ischemia of muscles during rest and exercise, possibly due to defective autoregulation of skeletal muscle blood flow, may explain the abnormally high lactate generation.


Cerebellar form of progressive multifocal leukoencephalopathy (PML).

A case of progressive multifocal leukoencephalopathy (PML) with selective involvement of cerebellum and brain stem is compared with nine other published cases. Recognition of PML presenting with ataxia before cerebral manifestations is stressed especially, since promising results with some antiviral drugs have been claimed.


[Criteria of the diagnosis and treatment of carotid atheromatosis].

This retrospective study concerning 102 patients was undertaken to study the therapeutic decisions in these patients when they presented with symptoms of cerebral vascular insufficiency, mostly from the territory of the carotid artery, either transient or accompanied by a deficit. The current literature on the subject is also mentioned. The clinical outcome with regard to the quality of life, seems to have been better in patients who were subjected to carotid endarterectomies than in those who received medical treatment.


Melanin containing neurofibroma: case report with evidence of Schwann cell origin of melanin.

This case report describes a melanin-containing neurofibroma involving a spinal nerve root. Electron microscopy of the tumor shows that neoplastic Schwann cells are capable of melanogenesis. Although this capability is suggested in the literature, few reports provide ultrastructural confirmation. The likely identity between reported "cellular blue nevi of spinal nerve roots" and nerve sheath tumors is discussed. It is possible that pigmented nerve sheath tumors behave more aggressively than nonpigmented ones, although it is debatable.