The projection of the lateral geniculate nucleus to area 17 of the rat cerebral cortex. IV. Terminations upon spiny dendrites.

The forms of the spiny dendrites in layer IV receiving degenerating thalamocortical axon terminals have been examined in serial thin sections. Reconstructions of segments of these dendrites show that the axon terminals synapse with both the dendritic spines and the dendritic shafts. No main shafts of apical dendrites of pyramidal neurons were found to synapse with the thalamic afferents, which are received mainly by spiny dendrites 1-2 micron in diameter, at least some of which appear to be the oblique branches of apical dendrites. The forms of these postsynaptic dendrites are so variable that is concluded they arise from more than one morphological type of neuron. The conclusion based on this and previous articles in the series is that most neuronal elements in layer IV which form asymmetric synaptic junctions are potential recipients of the thalamocortical afferents.


Development of neuromuscular junctions of fast and slow muscles in the chick embryo: a light and electron microscopic study.

The morphogenesis of neuromuscular injections (NMJ) was studied by electron microscopy in fast posterior and slow anterior latissimus dorsi muscles (PLD and ALD) of chick embryos. In 8 day embryos, the NMJ is already established in both types. In PLD at this stage, individual axons completely ensheathed by Schwann cell processes form NMJs with myotubes, whereas in ALD axon terminal lie adjacent to (and not separated by Schwann cell processes from) naked axons which are components of a nerve bundle. At 11-15 days, the number of profiles of axon terminals at each endplate increases in both PLD and ALD. In PLD, individual axon terminals are ensheathed by Schwann cells and often branch. In ALD, several axon terminals become ensheathed as a group by processes of a Schwann cell, along with a small number of adjacent naked axons. The individual axon terminals were confirmed by analysis of serial sections to originate from different preterminal axons. Thus, the increase in number of axon terminals in PLD may be due to extensive terminal branching, whereas in ALD it may be due to the arrival of other nerve fibres. From 16 days, each axon terminal in an endplate of ALD becomes individually ensheathed by Schwann cell processes. However, the property of polyneuronal innervation in each endplate is retained even in the adult muscle. The junctional sarcoplasm protrudes to separate individual axon terminals at certain developmental stages: the protuberances are thinner and more numerous in ALD than in PLD at 15-16 days. It is concluded that NMJ morphogenesis differs between PLD and ALD and that the differences reside mainly on the neuronal side.


Degeneration of varicose axons and their phagocytosis by smooth muscle cells.

Intramuscular varicose axons of the guinea-pig vas deferens were studied by electron microscopy after surgical and chemical denervation. The intervaricose segments disappear, and the varicosities become disconnected, spherical in shape and either swollen or more electron-dense. Other varicosities, presumably more advanced degenerative stages, appear as phagosomes in the cytoplasm of Schwann cells and of smooth muscle cells. Smooth muscle cells are extensively involved in the process of elimination of the degenerated nerve varicosities.


Volume composition of the lateral cervical nucleus in the cat. I. A stereological and electron microscopical study of normal and deafferentated animals.

The neuropil of the lateral cervical nucleus (LCN) has been studied by means of ultrastructural stereological methods. Estimates of the fractional volumes of axons, glial cells (three types), extracellular space, boutons, bouton mitochondria, dendrites, dendritic mitochondria, neuronal somata and blood vessels were calculated for four normal cats and eight cats which had been subjected to spinal deafferentation 2, 4, 9, and 14 days before perfusion. 14 days after operation the fractional volume of boutons and dendrites in the nucleus was considerably lower on the operated side, corresponding to a reduction of 67% and 64% respectively. The bouton reduction was higher than could have been expected from findings in earlier qualitative studies. The reduction in dendritic volume, which was already present after 4 days, had not been detected in earlier studies of the LCN. Dark dendrites were found both in normal animals and on the normal and operated sides in operated animals. The variation from animal to animal was great but the figures for the deafferented sides were significantly higher. The general value of the stereological technique in ultrastructural neuroanatomical research is discussed and it is concluded that quantitative methods are more sensive to small and gradual changes and should give a better estimation of transneuronal effects and of the amount of degeneration than purely qualitative methods.


Chronic occupational exposure to lead: an evaluation of the health of smelter workers.

After receiving reports of lead poisoning in two workers at a secondary lead smelter, we evaluated the health status of 38 current smelter workers and 87 of their household contacts by questionnaires, physical examinations, and laboratory tests. Fatigue, cough, and diarrhea were the most frequent symptoms in plant employees; each occurred in at least a third. The most frequent physical finding, hand tremor, occurred in 10 of 33 plant employees. Twelve employees had blood lead concentrations at or above 80 microgram/100 ml, and 17 others had blood lead concentrations at or above 60 microgram/100 ml. All physical signs possibly due to excess lead absorption were manifested by employees with blood lead levels of 60 microgram/100 ml or greater, with one exception. Household contacts of employees had few symptoms suggestive of excess lead absorption.


Asbestosis -- a diagnostic enigma: a personal view.

Although the carcinogenic properties of asbestos are presently attracting a good deal of attention, asbestosis is still the earliest lung disease resulting from exposure to it and its incidence in an exposed population is the most useful indicator of the degree of dust control exercised over a period of time. The diagnosis of asbestosis depends upon: (1) An adequate occupational exposure history. (2) Physical signs of pulmonary fibrosis. (3) Progressive radiological changes. (4) Confirmatory measurements of altered lung function. Asbestosis is a clinical entity and is readily diagnosed when all the above-mentioned criteria are met. Problems in diagnosis are encountered when one or more of the diagnostic criteria listed above cannot be substantiated. At the present time every effort is made to diagnose the disease in its early stages in the hope that removal from further exposure will prevent the direct and indirect complications.


The forced end-expiratory flow rate in chloromethyl ether workers.

Spirograms were made in 103 chemical workers, 72 of whom had been exposed for years to chloromethyl ethers to various degrees. The end-expiratory flow rate was below 60% of predicted in one-third of exposed men compared to only 3% of unexposed men. Smoking was a confounding factor. In 49 current cigarette smokers consuming less than one pack per day, the data suggested a dose-response relationship between chemical exposure and the frequency of low end-expiratory flow rate.


Impairment severity in seizure disorders: some suggestions for reliable assessment.

Severity of impairment in seizure disorders is typically difficult to assess because of the existence of seizure-free intervals of varying duration, often in the absence of neurological or other clinical signs. For purposes of determining degree of severity, clear documentation and description of seizures, as well as of any associated phenomena such as loss of sphincter control and the side effects of medication, are needed. Differentiation between primary and secondary seizure disorders is also important because the latter frequently are associated with other impairments. The approach to assessment advocated is based on the incidence and intensity of seizures remaining after maximum therapeutic control has been achieved. An assessment form has been developed which concisely summarizes salient case features. A composite case report is appended for the purpose of demonstrating use of the form. Instructions are in the Appendix.


Racial stratification of organochlorine insecticide residues in human adipose tissue.

The racial stratification of residues of total DDT equivalent, heptachlor epoxide, oxychlordane, dieldrin, beta-benzene hexachloride and lindane in human adipose tissue was studied. Samples of human adipose tissue were obtained from locations selected in the contiguous United States according to a stratified, proportionate-random survey design and chemically analyzed for selected organochlorine pesticides. The most marked case of racial difference in residue level was total DDT equivalent. Samples from Negros contained almost twice as much of this chemical as did samples from Caucasians. Racial stratification also was found in the frequency of lindane. Lindane was detected about twice as often in samples from Negros than in samples from Caucasians. Little racial differences were noted for residues of beta-benzene hexachloride, heptachlor epoxide, dieldrin and oxychlordane.


Responses of atrial mechanoreceptors to pulsation of atrial volume.

1. Firing patterns of single atrial fibres were monitored in order to study their sensitivity to rate of change of atrial volume and their dependence on receptor location in the atria.2. To that effect, sinusoidal fluctuations of volume (+/-1 ml.; 60/min) were superimposed on the natural pulsations of the heart of spontaneously breathing anaesthetized cats.3. Stimulus-response histograms revealed that maximal firing frequency of B-impulses preceded maximal volume change by 10-80 degrees (average 48+/-7 degrees (S.E.), thirteen right and left atrial receptors) indicating that sensitivity to rate of change of atrial volume at least equalled volume sensitivity.4. The rate sensitive component of B-firing increased with respect to the volume sensitive component when atrial filling diminished and was larger for high threshold receptors than for low threshold receptors (P<0.001).5. The A-bursts were not affected by atrial pulsing in eight out of nine anatomically localized receptors; inspiration prolonged the A-bursts of three receptors and advanced the timing of A-bursts with respect to the a-wave (10-50 msec) of all nine receptors.6. About half of all anatomically localized receptors were traced to the interatrial septum. These septal receptors differed from right and left atrial receptors as follows: (a) they were exclusively of the AB-type (fired during atrial a- and v-wave); (b) their B-firing rates were significantly lower (P<0.05); (c) A-firing patterns remained largely unaffected by respiration or by atrial pulsing; (d) they signalled volume changes of either atria; (e) no association of rate sensitivity with threshold was detected (P>0.95). The physiological role of septal receptors remains to be elucidated.7. It was concluded that B-fibres were sensitive to both change and rate of change of atrial volume; their role as sensors of venous return is suggested strongly. Results further suggested that A- and B-firing are determined largely by the location of atrial stretch receptors.


Arterial chemoreceptors, ventilation and heart rate in man.

1. Transient changes of heart rate (HR) and ventilation were recorded following step changes in alveolar gas composition in three healthy subjects. From a steady state of normo- or slightly hypercapnic hypoxia (PA,CO2 38-46 torr, PA,O2 50-60 torr) arterial chemoreceptor stimulation was transiently relieved by breathing a CO2-free mixture for two breaths, either pur O2 (causing a fall in PA,CO2 and a rise in PA,O2; O2 test) or a low O2 mixture (causing a fall in PA,CO2 without any change in PA, O2; CO2 test). For both test types ventilation was either allowed to change freely ('free-breathing' tests) or was consciously maintained at the pre-test level by the subjects ('controlled-breathing tests). The circulatory delay from the lungs to the ear was measured with a sensitive ear oximeter. 2. In all 'free-breathing' tests ventilation decreased significantly after a mean latency of 5.2 sec; the average lung-ear circulation time was 4.9 sec. HR increased slightly above pre-test levels in eighty-one of one hundred and four tests of all types, the changes being significant after a latency identical to that of the ventilatory changes. Except in the 'controlled-breathing' CO2 tests this early tachycardia was followed by a decrease in HR within the following 5-6 sec. 3. These findings indicate that the primary effect of withdrawal of arterial chemoreceptor stimulation in conscious man as in the anesthetized animal is tachycardia. The secondary development of bradycardia in 'free-breathing' CO2 tests is probably due to the operation of a lung reflex sensing changes in ventilation. The absence of bradycardia in 'controlled-breathing' CO2 tests and its presence in 'controlled-breathing' O2 tests, finally, suggest that relief of systemic hypoxia causes a slowing of the heart not due to lung reflexes but to some other mechanism which operates with a latency nearly twice as long as the arterial chemoreflex.


The rabbit anococcygeus muscle and its response to field stimulation and to some drugs.

1. The response of the rabbit anococcygeus muscle to field stimulation of its intramural nerves and to some drugs has been examined and compared with results previously obtained in the rat and the cat. 2. The rabbit muscle possesses an adrenergic innervation as demonstrated histologically by the Falck and Hillarp fluorescence technique. This innervation is sparser than in the rat or cat. 3. In vitro the muscle usually shows little tone but if suitably stretched will develop a maintained contraction. The response to field stimulation depends on the level of tone. When this is low purely motor responses are obtained. In the presence of tone the response depends on its level and the frequency of stimulation; low frequencies are purely inhibitory, with increasing frequency the response becomes biphasic and high frequencies produce a purely motor response. The higher the tone the more prominent the inhibitory components. Guanethidine 10(-5)M abolishes the motor component. 4. The muscle is caused to contract by noradrenaline, acting through alpha receptors, by hista,ome actomg through H1 receptors and by 5-hydroxy-tryptamine. Part of the effect of the latter appears to be due to the release of noradrenaline. 5. The muscle is caused to relax by acetylcholine acting through muscarinic receptors, by isoprenaline through beta receptors, by histamine in the presence of mepyramine through H2 receptors and by ATP and bradykinin. 6. The significance of these findings for the motor and inhibitory innervation of the muscle is discussed.


Some electrical properties of the rabbit anococcygeus muscle and a comparison of the effects of inhibitory nerve stimulation in the rat and rabbit.

1. Simultaneous recordings of mechanical activity and membrane potential of individual smooth muscle cells have been made in the rabbit anococcygeus muscle and the effect of field stimulation on these examined.2. In the absence of tone the mean resting membrane potential was - 48 mV. In the stretched muscle spontaneous tone and rhythmic activity quite frequently appeared and this was associated with depolarization of the muscle cells.3. The response to field stimulation depended on the frequency of stimulation, the level of membrane potential and the presence of myogenic tone. The usual response to single pulses or low frequency stimulation was a hyperpolarization of up to 30 mV (mean 14+/-6.8 mV) after a latency of 185 msec and accompanied by muscle relaxation. Higher frequencies (over 8 Hz) produced an initial depolarization often with a spike potential and followed by hyperpolarization. The mechanical response in these instances was contraction or contraction followed by relaxation. At all frequencies rebound depolarization and an associated contraction followed the end of stimulation).4. Phentolamine (5x10(-6)M) and guanethidine (10(-6)M) blocked the initial depolarization and contraction but had no effect on hyperpolarization, muscle relaxation or rebound depolarization and contraction.5. The effect of field stimulation in the presence of guanethidine (4x10(-5)M) was re-examined in the rat anococcygeus. Single pulses were ineffective, repetitive stimulation produced muscle relaxation but no hyperpolarization comparable to the rabbit. Any oscillations in membrane potential were damped during field stimulation and sometimes a small hyperpolarization was produced with a maximum amplitude of 13 mV and a mean of 1.9+/-1.2 mV.6. The transmembrane potential at the peak of hyperpolarization in the rabbit was rarely more than -70 mV. Passive displacement of the membrane potential by current pulses altered the amplitude of the hyperpolarization and suggested that there was a reversal potential at between -80 and -90 mV.7. No change in input resistance could be measured during inhibitory nerve stimulation in either the rabbit or the rat but measurements based on electrotonic potentials indicated a reducation in membrane resistance, small in the rat but greater in the rabbit.8. These experiments suggest that in both species muscle relaxation is associated with an increase in ionic permeability and a move, at least in the rabbit muscle, towards an equilibrium potential of -80 to -90 mV. In view of the much smaller effect in the rat it is not clear whether this is the cause or at least the sole cause of the muscle relaxation.


The reorganization of synaptic connexions in the rat submandibular ganglion during post-natal development.

1. The innervation of neurones in the submandibular ganglion of neonatal and adult rats has been studied with intracellular recording, and light and electron microscopy. 2. Intracellular recordings from neurones in isolated ganglia from adult animals showed that about 75% of the ganglion cells are innervated by a single preganglionic fibre. 3. However multiple steps in the post-synaptic potential (about five on average) were elicited in ganglion cells from neonatal animals by graded stimulation of the preganglionic nerve. The same result was obtained when the preganglionic fibres were stimulated at their emergence from the brainstem, indicating that neonatal neurones are innervated by several different preganglionic nerve cells. 4. The number of preganglionic fibres innervating individual ganglion cells gradually decreased during the first few weeks of life, and by about 5 weeks each ganglion cell was generally contacted by a single preganglionic axon. 5. Synapses were made on short protuberances in the immediate vicinity of the neuronal cell bodies in both neonatal and adult ganglia as shown by staining presynaptic boutons with the zinc-iodide osmium method, injection of horseradish peroxidase into ganglion cells, and electron microscopical examination. 6. Electron microscopical counts of synaptic profiles per ganglion cell perimeter showed that the number of synaptic contacts made on ganglion cells actually increased during the first few post-natal weeks, when the number of axons innervating each neurone was decreasing. 7. These results show that in the rat submandibular ganglion there is a reorganization of neuronal connexions during the first few weeks of life which results in a transition from multiple to generally single innervation of ganglion cells.


Thin-fibre receptors responding to mechanical, chemical, and thermal stimulation in the skeletal muscle of the dog.

1. Unitary activities of muscular thin fibre afferents, which were not sensitive to muscle stretching, were recorded from the nerve of the medial gastrocnemius muscle of the dog. Responses to mechanical stimulation, intra-arterial injection and local application of chemical solutions, and thermal stimulation of the surface of the muscle were studied. It was observed that polymodal receptors which responded to all types of stimulation existed in the thin fibre afferents of the muscle.2. The receptive area of these units tested by mechanical stimulation was spot-like and appeared to be located not only on the surface but in the midst of the muscle.3. The mechanical response varied among these units with respect to the threshold and the pattern of discharges.4. In these units, NaCl, KCl, and bradykinin consistently evoked responses, with differences in the latencies and discharge patterns, while solutions of histamine, acetylcholine and sodium citrate caused responses less consistently and less effectively. In the stretch receptors, chemical stimulation applied in the same way as tested in the thin fibre afferents produced quite different features in their responses.5. Heating the receptive area of the muscle surface caused responses in twenty-five out of thirty-six units, which were sensitive both to mechanical and to chemical stimulations. The threshold varied from 38.0 to 48.3 degrees C, with a mean of 43.1 degrees C for C fibre units and 41 degrees C for A-delta fibre units.6. The responses to heating were consistently obtained in the units responding to the surface application of chemical solutions. However, the above response was never obtained in the units which did not respond to surface chemical stimulation but responded to intra-arterial injection. These results suggest a large population of polymodal receptors in the muscular thin fibre afferents.


Kinetic analysis of sodium and chloride influxes across the gills of the trout in fresh water.

1. Na and Cl intake through the gill of the perfused head of trout were studied in fresh water with (10(-5)M) or without adrenaline in the perfusing solution. 2. Ionic influxes occur exclusively across the lamellae in fresh water while in the sea-water adapted trout part of salt entry is extralamellar. 3. In absence of adrenaline, Na and Cl enter the gills at the same rate (respectively 6.9 +/- 1.30 and 6.6 +/- 1.55 muequiv/hr. 100 g). Adrenaline (10(-5)M) increased the Na influx to 47.8 +/- 4.12 muequiv/hr. 100 g, a value similar to that observed in vivo. The Cl influx remains unchanged however (6.3 +/- 2.40 muequiv/hr. 100 g), a value much smaller than that found in vivo. 4. Radioactive loading experiments coupled with unloading experiments allowed the determination of the relative permeabilities of the serosal and mucosal barrier for Na+ and Cl-. For both ions, the basal membrane is less permeable. Adrenaline by increasing the Na permeability across the apical barrier enhances the active Na pumping through the basal membrane. 5. Intracellular Na and Cl exchangeable pools were calculated. They represent less than 1% of the total ionic content of the epithelium. Adrenaline increased by sixfold the Na pool without modifying the Cl pool.


The effects of external cations and ouabain on the intracellular sodium activity of sheep heart Purkinje fibres.

1. The intracellular Na activity of sheep heart Purkinje fibres has been measured using recessed-tip Na(+)-sensitive glass micro-electrodes.2. The internal Na activity was 7.2 +/- 2.0 mM (mean +/- S.D., n = 32) at the normal external Na concentration, [Na](o), in these experiments of 140 mM (equivalent to an external Na activity of 105 mM). The equilibrium potential for Na across the fibre membrane was therefore approximately + 70 mV.3. When the [K](o) was altered the internal Na activity changed, reaching a new level within about 20 min. Increasing the [K](o) from 4 to 25 mM decreased the internal Na by approximately 30%, while decreasing the [K](o) from 4 to 1 mM increased internal Na by 20%.4. The removal of external K produced an easily reversible increase in the internal Na with an initial rate equivalent to a concentration change of 0.24 +/- 0.07 m-mole/min (mean +/- S.D., n = 8).5. Ouabain produced increases in the internal Na activity that were only very slowly reversible. The threshold concentration for producing an increase was approximately 10(-7)M.6. When [Na](o) was reduced the internal Na activity fell rapidly with a single exponential time course (time constant 3.3 +/- 0.8 min, mean +/- S.D., n = 16) to a new, relatively stable level. The recovery of internal Na on return to the normal [Na](o) did not have a simple time course. It was normally complete within 10-30 min.7. The relationship of the stabilized level of the internal Na activity to the [Na](o) was approximately linear over the range 140-14 mM-[Na](o). When [Na](o) was reduced from 140 to 14 mM the internal Na activity fell by 72 +/- 5% (mean +/- S.D., n = 21).8. When the [Na](o) was reduced, the decrease in the internal Na activity was partially inhibited by Mn or by removal external Ca.9. When the [Ca](o) was altered over the range 0.2-16 mM the internal Na activity was reduced by approximately 50% for a tenfold increase in the [Ca](o).10. The relationship between internal Na and contractility is discussed.


Specific responses of rat raphé neurones to skin temperature.

1. The responses of single neurones in the nuclei raphés magnus, medianus, dorsalis and pontis to changes in skin temperature were recorded in rats anaesthetized with urethane. Skin temperature was altered by means of a water-perfused jacket. 2. Of 210 neurones studied, thirty-five were specifically excited by warming the skin whilst twenty were cold responsive. The greatest proportion of cells responding to skin temperature were in the nucleus raphé magnus, whilst few neurones in the raphé dorsalis and pontis were influenced. 3. The warm units had peak activity at a mean skin temperature of 37.7 degrees C whilst the cold cells had a corresponding maximal rate at 29.0 degreet C. Mechanical and noxious peripheral stimulation, blood pressure changes and temperatures other than that of skin did not affect the neurones. 4. The neurones influenced by skin temperature were histologically verified as being within the raphé system. 5. LSD inhibited all neurones tested, indicating that the cells were serotonergic. 6. The responses to skin temperature were unchanged in rats with midcollicular sections suggesting an ascending thermal system. 7. The results suggest that any involvement of 5-HT in central thermo-regulation is in terms of an afferent thermal pathway mediated by serotonergic raphé neurones.


An analysis of the anatomical basis for the mechanical response to motor nerve stimulation of the rat vas deferens.

1. An anatomical basis was sought for the biphasic motor nerve response of the rat vas deferens. The motor nerve pathway to the tissue was stimulated at different points between the vertebral outflow and the intramural fibres, in the pithed rat and in isolated tissues, to examine the possibility of two anatomically separate groups of neurones. Different preparations of the isolated tissue were devised to detect whether different groups of smooth muscle fibres contributed to the two phases.2. The fibres mediating both phases of the response arose from the upper lumbar vertebral outflows. Both phases were elicited by pre- or post-ganglionic stimulation and could be depressed by hexamethonium. In the pithed rat or with hypogastric nerve stimulation in the isolated tissue, however, the initial ;twitch' phase was relatively resistant to such blockade.3. When the rat vas deferens was perfused through the lumen in situ or in vitro, the perfusion pressure response to motor nerve stimulation exhibited two phases similar to those of the longitudinal contractile response.4. Isolated rat vasa were bisected into portions, each of which was stimulated and longitudinal tension was recorded. The proportions of the two phases of the response varied along the length of the tissue. At the prostatic end the total response was relatively weak with a dominant ;twitch' and at the epididymal end the two phases were comparable in magnitude. The distribution of adrenergic nerve terminals within the muscle layers also varied along the length of the rat vas deferens.5. The effects of drugs were investigated on the motor responses of the above preparations. The ;twitch' phase was relatively susceptible to blockade by reserpine and lysergic acid diethylamide and the ;secondary' phase to phentolamine with both equally sensitive to guanethidine. Each phase had similar susceptibilities to blockade irrespective of which part of the tissue was involved.6. It was concluded that two types of nerve-muscle transmission may be involved in the rat vas deferens with the proportion of each varying along the length of the tissue but both displaying pharmacological characteristics of adrenergic fibres.


Changes produced by chronic denervation in the temperature-dependent isometric contractile characteristics of rat fast and slow twitch skeletal muscles.

1. Influence of temperature (range 20-35 degrees C) on the isometric contractile properties of normal and chronically denervated fast-twitch extensor digitorum longus and slow-twitch soleus muscles of the rat have been studied in vitro. 2. The times to peak twitch tension of denervated muscles were longer than those of normal in both types of muscle. The denervated muscles were, however, identifiable as 'fast-twitch' or 'slow-twitch' throughout the entire temperature range. 3. The twitch tension/tetanic tension ratios of the denervated muscles at 35 degrees C were significantly higher than those of the normal muscles. 4. The twitch tension of the normal extensor digitorum longus muscles increased whereas that of the normal soleus muscles decreased with cooling from 35 to 20 degrees C. Such a qualitative difference did not exist between the denervated extensor digitorum longus and soleus muscles. The twitch tensions of both denervated muscles decreased with cooling. 5. Cooling to 20 degrees C resulted in a greater fall in tetanic tension in the denervated than in the normal muscles.


The response to distension of the pulmonary vein-left atrial junctions in anaesthetized dogs after section of the rostral medulla.

1. Distension of the pulmonary vein-left atrial junctions caused an increase in heart rate and a transient decrease in mean arterial pressure. 2. Section of the brain stem at the level of the inferior cerebellar peduncle (rostral medulla) caused a decrease in mean arterial pressure. 3. Section of the rostral medulla had no effect on either the magnitude or the time course of the reflex response to pulmonary vein distension. 4. Administration of propranolol after section in the rostral medulla reduced the reflex increase in heart rate in response to pulmonary vein distension by an amount similar to that previously described in intact and decerebrate animals. 5. Bilateral cervial vagotomy prevented the reflex response to pulmonary vein distension.


Effects of medullary lesions on arterial baroreceptor reflexes and responses to distension of pulmonary vein-left atrial junctions in anaesthetized dog.

1. In anaesthetized dogs lesions of 4 mm diameter centred on the obex were placed in the medulla dorsal to the hypoglossal nucleus. 2. Placing of the lesions almost totally abolished the reflex responses to distension of the pulmonary vein-left atrial junctions and to low intensity stimulation of the aortic nerv. The reflex response to high intensity stimulation of the aortic nerve was reduced and the reflex response to carotid artery occlusion remained unaltered. 3. Mid-collicular decerebration did not affect the results. 4. The results are consistent with a hypothesis that afferents from the carotid sinus baroreceptors synapse in the nucleus of the tractus solitarius rostral to the obex, whereas afferent fibres from the aortic baroreceptors and atrial receptors synapse in the intermediate portion of the nucleus of the tractus solitarius close to the obex.


The role of adrenergic receptor blockade in serotonin-induced changes in the pulmonary circulation.

1. In dogs i.v. injection of serotonin caused a rise in pulmonary artery pressure and pulmonary arteriocapillary resistance that persisted even after alpha- and beta-adrenergic receptor blockade; pulmonary venous resistance also increased, but this was abolished by pretreatment with either propranolol or phenoxybenzamine. 2. The injection of serotonin into the ascending aorta produced an immediate rise in systemic, pulmonary arterial and pulmonary venous pressures and pulmonary venous resistance. After phenoxybenzmine, the rise in systemic and pulmonary arterial pressures remained unchanged, but previously observed increases in pulmonary venous pressure and resistance were blocked. In contrast, propranolol failed to abolish the rise in pulmonary venous resistance after serotonin injection into the ascending aorta. 3. These results confirm the observation that the vasoconstrictor effect attributed to intravenously injected serotonin on the arterial side of the pulmonary circulation is independent of the known sympathetic pathways. The data suggest that the pulmonary venoconstriction induced by intravenous serotonin is of reflex origin, abolished by alpha and beta receptor blockade, whereas the efferent arm of the reflex pulmonary venoconstriction following injection of serotonin into the ascending aorta is mediated via alpha-adrenergic receptors.


Left ventricular mechanoreceptors: a haemodynamic study.

1. To study the function of the left ventricular mechanoreceptors, a working left ventricle preparation was devised in dogs which permitted control of pressure and flow of the isolated perfused coronary circulation and of the flow of the isolated, separately perfused systemic circulation. The systemic circulation was perfused at a constant rate so that changes in systemic pressure reflected changes in systemic resistance.2. Increases in myocardial contractility produced by injection of catecholamines into the isolated, perfused coronary circulation produced a fall in the pressure (resistance) of the isolated, separately perfused (at a constant rate) systemic circulation.3. Completeness of isolation of the coronary and systemic circulations was shown by the marked difference in appearance times between the reflex hypotensive responses from catecholamine injections into the isolated coronary circulation and the direct hypertensive response from a similar injection when the circulations were connected as well as by the marked difference between the pressure pulses recorded simultaneously on both sides of the aortic balloon separating the two circulations.4. Myocardial beta receptor blockade produced by injection of propranolol into the isolated coronary circulation abolished or attenuated the changes in left ventricular myocardial contractility as well as the subsequent hypotensive responses following the similar injection of catecholamines.5. Electrical stimulation of a sympathetic nerve innervating the heart resulted in increases in left ventricular myocardial contractility and subsequent systemic hypotensive responses indistinguishable from those following injection of catecholamines.6. That distortion of the mechano- or stretch receptors in the left ventricular myocardium was the cause of the hypotensive responses was demonstrated by increasing left ventricular myocardial contractility by mechanically obstructing the left ventricular outflow which produced hypotensive responses similar to those following the injection of catecholamines or nerve stimulation.7. Bilateral high cervical vagotomy abolished the hypotensive responses following injection of catecholamines into the isolated coronary circulation or following left ventricular outflow obstruction in all but one instance, indicating the importance of vagal fibres to the afferent arm of the reflex.8. It is suggested that the left ventricular mechanoreceptors function normally to reduce the peripheral resistance in order to prepare the systemic circulation to receive the left ventricular output and, especially during exercise, to prepare the systemic circulation to receive the augmented cardiac output with a minimum alteration in the systemic blood pressure and to distribute this augmented output preferentially to the skeletal muscles.


The digestion and transmission of labelled immunoglobulin G by enterocytes of the proximal distal regions of the small intestine of young rats.

Density gradient centrifugation of samples prepared from proximal gut homogenates after intra-lumenal injection of 125I-labelled IgG, was used to prepare batches of IgG fragments according to sedimentation coefficients. 2. Ultrafiltration was employed to partition the radioactivity in the vascular compartments, viscera and carcasses of rats aged 14-15 days, 2 hr after the injection of standard doses of labelled IgG into the proximal and distal regions of the small intestine. 3. Radioactive samples prepared by these methods were re-introduced into young rats by intra-cardiac injection, and the rate at which they were removed from the vascular compartment was assessed. 4. Proximal enterocytes transmitted about 39% of the IgG which had been removed from the intestine in intact form. Most of this was retained in the vascular compartment; they degraded up to about 57% of the total removed into fragments less than 1000 mol. wt. and about 4% into intermediate sized fragments. 5. Distal enterocytes degraded almost 90% of the IgG processed into fragments less than 1000 mol. wt., about 8% as fragments greater than 100,000 mol. wt. 6. Fragments, of all sizes, were cleared rapidly from the circulation into the viscera and carcass. 7. The relevance of these results to protein transmission and digestion by the rat small intestine is discussed.


Increased urinary kallikrein excretion during prostaglandin E1 infusion in anaesthetized dogs and its relation to natriuresis and diuresis.

. The effect of intra-arterial prostaglandin  E1 (PGE1) infusion on urinary kallikrein, sodium, potassium and water excretion was studied in normal anaesthetized dogs. 2. Infusion of PGE1 caused a dose-related increase in urinary excretion of kallikrein, sodium, potassium and water as well as an increase in renal blood flow (R.B.F.) and a fall in urinary osmolality and renal vascular resistance. 3. The changes occurred in the absence of appreciable changes in inulin clearance (Cin), arterial blood pressure, haematocrit, and plasma sodium and potassium concentrations. 4. The increased urinary kallikrein excretion correlated positively with  the natriuresis, diuresis and kaliuresis and the increase in renal blood flow, but negatively with the urinary osmolality and renal vascular resistance. 5. It is concluded that renal kallikrein is involved in the renal response to arterial infusion of PGE1.


Rabbit placental clearing-factor lipase and transfer to the foetus of fatty acids derived from triglycerides injected into the mother.

1. Lipase activity was measured in rabbit placental tissue fragments in late pregnancy. The activity in incubated tissue was greater with heparin (69%), reduced by NaCl (90%), but not affected by acetone or ether. 2. Pregnant rabbits (28-days gestation) were given triglyceride emulsions intravenously and the change in profile of fatty acids in the maternal and umbilical artery and vein plasma free fatty acid (FFA) measured. 3. Those fatty acids predominant in the emulsion were higher in concentration in the umbilical vein FFA than in the maternal plasma FFA  and the venous-arterial difference was altered such that the placental transfer of FFA was enriched in a pattern corresponding to the profile of the fatty acids in the emulsion. 4. It is concluded that (i) the rabbit placenta shows considerable lipase activity and the lipase has the same characteristics as clearing-factor (lipoprotein) lipase, (ii) triglyceride infused into the mother is taken up by the placenta and hydrolysed, and (iii) the fatty acids so released pass through the placenta and are taken up by the foetus.


Kinetic evaluation of the Na-K pump reaction mechanism.

1. The ouabain-sensitive K influx was measured at varying external K concentrations ([K]o) and at several fixed internal Na concentrations ([Na]c). The cells were nominally K-free and the solutions Na-free. Both the apparent maximal velocity (VM) and the apparent Michaelis constant for K (KK) increased as Nac increased. The ratio app. VM/app. KK increased with increasing Nac. 2. The ouabain-sensitive Cs influx was measured at varying external Cs concentrations and at several fixed Nac in K-free cells and Na-free solutions. Both app. VM and app. Kcs increased as Nac increased and the ratio app. VM/app. Kcs increased with increasing Nac. 3. The data were evaluated in terms of ping-pong model and a simultaneous model for the pump reaction mechanism. The simultaneous model described the data adequately and the ping-pong models did not. 4. The K influx was measured at varying external K concentrations in solutions containing Na and at a low and high Nac; the cells contained K. The relation between the pump rate and the external K concentration was sigmoid. A Hill equation was fitted to the data. KK was higher in the high Nac cells, but the Hill coefficient (n) was not altered as Nac increased. 5. The K influx was measured at varying internal Na concentrations and two fixed external K concentrations; the cells contained K. The relation between the pump rate and Nac was sigmoid. When a Hill equation was fitted to the data, it was found that KNac was higher at the high external K concentration, but n was the same at both K concentrations.


A quantitative study of the effects of cholinergic drugs on carotid chemoreceptors in the cat.

1. Conflicting qualitative evidence exists concerning the effects on chemoreceptor activity of some drugs which influence the cholinergic system. Quantitative evidence has been obtained in the present study which should resolve the conflict. 2. Experiments were performed in pentobarbitone-anaesthetized cats in which the activity of chemoreceptor units in the sinus nerve was used to assess chemoreceptor responses. The effects of drugs on responses to I.A. ACH and NaCN were determined from dose-response data obtained from several animals and expressed as mean dose ratios 3. The chemoreceptor response to ACh was slightly inhibited by atropine, alpha- and beta-bungarotoxin and HC-3, almost completely suppressed by mecamylamine, and markedly potentiated by physostigmine. 4. Concomitant responses to NaCN were unaffected by atropine, beta-bungarotoxin, mecamylamine or physostigmine. There was a slight inhibition following alpha-bungarotoxin and a potentiation after HC-3. 5. The results do not support the theory that ACh is an excitatory sensory transmitter in the carotid body.


Are there functionally important temperature sensors in the right heart or lungs?

1. In conscious rabbits, paired hot or cold infusions were given into the left atrium or jugular vein. For each pair of infusions the volume and temperature of the fluid was identical. The time course of the displacement of brain temperature was measured. 2. The magnitude of the displacement of brain temperature was not influenced to any major extent by the route of infusion. 3. This evidence suggests that there are no temperature sensors of any importance in the right heart or lungs.


[Effect of ethacrynic acid on contractility and Ca flux of guinea pig taenia coli smooth muscle (author's transl)].

The effects of ethacrynic acid (ETCA) which has been known as an -SH groups inhibitor on the contractility and the Ca flux of guinea pig taenia coli were investigated. The results obtained were as follow: 1) Contractures induced by 10(-4) M ACh, or the tonic component of 150 mM K-contractures were markedly suppressed by previous treatment with a low concentration (2 X 10(-4) M) of ETCA for 40 min. Conversely with the same treatment, the phasic component of this K-contracture was only slightly suppressed. The inhibitory effects of ETCA in both cases were reversed by the repetitive washing out of ETCA from taenia coli with normal tris-buffered solution. 2) ETCA, at concentrations higher than 10(-3) M, more markedly inhibited the ACh-, and the K-contractures. In this case these inhibitions were irreversible. 3) Cysteine in an equimolar concentration of ETCA prevented the inhibitory effects of ETCA on both contractures. 4) ETCA (10(-4) M) inhibited the ACh-contracture in Ca2+-free isotonic KCl solution to approximately the same degree as that in normal solution. 5) Inhibition of ACh-contracture by ETCA in Na+-free isotonic LiCl solution was less than that in normal solution. 6) ETCA (2 X 10(-4), or 10(-3) M) markedly stimulated 45Ca efflux from taenia coli in 20 mM Ca-EGTA tris-buffered solution. 7) 45Ca efflux acceleration by ETCA in Na+-free (replaced by Li+) 20 mM Ca-EGTA tris-buffered solution was less than that in 20 mM Ca-EGTA tris-buffered solution. These results may be explained by assuming that the inhibitory effect of ETCA on ACh-contracture can be attributed to the depletion of stored intracellular Ca and the acceleration of Ca efflux as a result of ETCA treatment.


Tails of Tetrahymena.

The source of force generation of beating cilia and flagella is an interaction between the doublet microtubules mediated by the dynein-1 arms which cause the doublets to slide relative to one another. Previously, were domonstrated direct sliding of Tetrahymena ciliary axonemes by dark field light microscopy. In this paper, the results of such an experiment have been captured on a polylysine-coated grid surface for whole-mount electron microscopy. Image in which a constant polarity. To produce the observed displacement, the direction of the dynein-1 arm force generation must be from base to tip, so that the doublet (n), to which the arms are attached, pushes the next doublet (n + 1) toward the tip. In addition to the functional polarity, the dynein-1 arms are found to have a structural polarity: they tilt toward the base when viewed along the edges of the A-subfiber. A scheme is presented which reconciles the finding of a single polarity of active sliding with the geometry of microtubule tip displacement of bent cilia.


Steady-state oxygen kinetics of terminal oxidases in Trypanosoma mega.

Steady-state oxygen kinetics of Trypanosoma mega reveal the presence of 3 oxidases. These include an oxidase which is sensitive to salicylhydroxamic acid (SHAM) but insensitive to sodium azide. This oxidase could be the L-alpha glycerophosphate oxidase present in bloodstream trypanosomes. In addition, and oxidase is present wthich is azide-sensitive but SHAM-insensitive. This oxidase is inhibited by CO and is probably cytochrome aa3. A 3rd oxidase is insensitive to both azide and SHAM but is inhibited by CO and is possibly cytochrome o. Reciprocal plots of T. mega reveal the presence of 2 oxidases that are inhibited by CO. These results are discussed in the light of previous evidence suggesting the presence of several oxidases and a branched electron transport system in T. mega.


Octadecenoic fatty acids and their association with hemolysis in malaria.

Octadecenoic fatty acids have been implicated in prehemolytic and hemolytic phenomena associated with malaria. Oleic [18:1 (n-9)] and cis-vaccenic [18:1 (n-7)] acids were found and quantified in the major neutral and phospholipids of the erythrocytes and plasmas of normal and Plasmodium lophurae-infected ducks, and in the parasite itself. The octadecenoic fatty acids were elevated over normal values in the major phospholipid classes of infected erythrocytes, in the erythrocyte-specific alkoxy phosphatidylethanolamine of infected erythrocytes, and in the plasma unesterified fatty acids, triacylglycerols, cholesterol esters and phosphatidlycholine of infected ducklings. Oleic acid was the major fatty acid of P. lophurae (33% total lipid fatty acid). Theoretical considerations of octadecenoic fatty acid modifications of erythrocyte membrane structure and function in malaria are discussed.


Carbohydrate composition of variant-specific surface antigen glycoproteins from Trypanosoma brucei.

The carbohydrate of variant-specific surface antigen glycoproteins from bloodstream forms of 13 cloned variants of Trypanosoma brucei was analyzed by gas-liquid chromatography. The glycoproteins contained from 6 to 17% carbohydrate by weight, and all contained the same 4 sugars: mannose, galactose, glucose, and glucosamine (probably as N-acetylglucosamine). The glycoprotein from variant 048, strain 427 contained (+20%) 11 mannose, 4 galactose, 4 glucose, and 5 glucosamine residues/mole of glycoprotein (molecular weight 65,000). Glucose was an intergral component of the glycoproteins, not dissociable by sodium dodecyl sulphate, 8 M urea, or 1 M acetic acid. Some of the glucose was dissociated by trichloroacetic acid. Most of the glycoproteins formed precipitin with concanavalin A in Ouchterlony double diffusion, but none formed such bands with wheat germ agglutinin or Ricinus communis lectin (molecular weight 120, 000).


Subcellular effect of cytochalasin B and dimethylsulfoxide on Paramecium aurelia.

Paramecium aurelia syngen 4, stock 57 (sensitve) cultivated in Cerophyl infusion were exposed to cytochalasin B (CB) and dimethylsulfoxide (DMSO), the solvent for CB, to distinquish between the effects of these agents on a cellular system. DMSO significantly inhibited survival, fission rate,, [3H]leucine incorporation, and cell size. CB-treated cells generally and slower division and poorer survival rates than cells exposed to the equivalent DMSO concentration, although the [3H]leucine incorporation was generally greater at the lower CB concentrations than for DMSO alone. As seen by electron microscopy and a new glycerination technic for observing polysomes, DMSO caused nuclear (nucleolar, chromatin) abnormalities as well as membrane degradation and polysomal breakdown: CB caused the formation of aberrant membrane structures and ribosomal tetramers, crystals, and tubes.


[Semiology of benign diseases of the breast in mammography (author's transl)].

Mammography is a basic examination which must never be dissociated from the clinical background. A statistical blind study of 330 cases shows that only well definite syndroms are reliable. The presence of absence of a single sign has no value. Difficulties arise in the diagnosis of suspect nodule in a dense dystrophic breast. Hydratation of the connecting tissue is a fundamental concept for analysis of mammographic pictures. The densities change according to hormonal influence, growth of dystrophy and specific signs of fibrillary or hyalin fibrosis. A histological study of serial cuts of the breast shows that the must reliable signs are found in the center of the nodule ande immediately around it. As in the histological study, serial cuts are indispensable in X-ray examination. Tomography improves the examination of dystrophies.


[Study of the liver by computerised tomography. Assessment of one years experience involving 1,480 investigations (author's transl)].

During a period of one year, and in two departments with identical equipment, 1,480 underwent examination of the liver by computerised tomography (C. T.). A critical analysis of the method is made, based upon the diagnostic results obtained as well as the errors and gaps noted. After describing the normal liver, the authors give the "C. T. appearances" of the main hepatic conditions, based upon correlation with macroscopic pathological findings.


[The echotomographic study of the vessels of the liver and the biliary tract (author's transl)].

As long as a clearly defined protocol is followed, exploration of the hepatic veins and biliary canals by echotomography (grey scale) is practically always possible. It should be incorporated in any echotomographic study of the hepatic parenchyma and reciprocally. This method of investigation is harmless, rapid, reproducible and low in cost.


[The diagnostic possibilities and limitations of arteriography in necrosed carcinomas of the kidney (author's transl)].

On the basis of a review of 186 cases of carcinoma of the kidney studied by arteriography in the Department of Radiology for Diseases of the Urinary Tract at Necker Hospital, the authors drew the following conclusions: 1. The diagnosis of carcinoma could be affirmed in the very great majority of cases and suspected in the others. 2. There were no instances of a reassuring false diagnosis (cyst). 3. A precise, rigourous and faultless technique, perfectly demonstrating the exteriorised part of the mass and attentive, thorough and careful interpretation of the films obtained, in particular with regard to the mass in its exteriorised portion, are always essential in order to obtain such results. In particular, the presence of a vascularisation of a discontinuous opaque band at the periphery of the mass in its exteriorised part indicates a strong suspicion of a necrotic malignancy and under no circumstances is an unreserved diagnosis of a cyst possible. 4. Diagnostic errors in the sense of false positives involving certain "thick-walled" cysts should be eliminated by pre-operative needle puncture. 5. The authors conclude by describing the method of radiological exploration which they feel to be desirable in practice following the discovery of a renal mass by intravenous pyelography.


[Tomodensitometric visualization of the pituitary gland in a case of empty sella tucica (author's transl)].

The authors describe a method of using tomodensitometry, after intravenous injection, to demonstrate pituitary remnants in a case of empty sella turcica.


[Pseudo-neoplastic sigmoid diverticulitis from radiology to diagnosis (author's transl)].

Pseudo-neoplastic sigmoid diverticulitis, a rare clinical form of pseudo-tumoural sigmoiditis, is characterised by the difficulty of its clinical, radiological, endoscopic and even per-operative diagnosis. None of these various phases in study may suffice to eliminate the possibility of an associated carcinoma. The diagnosis may be made by opening the operative specimen, but this is too late in time. The appearance of the bladder, rather than misleading the diagnosis, may provide arguments in favour of the benign nature of these pseudo-tumours.


[Pseudo-polypoid forms of crohn's disease (author's transl)].

Crohn's disease with a predominantly pseudopolypoid presentation is a rare form. The inflammatory polyps are of highly variable topography. They may be located in the colon and the ileum. There are diffuse and localised forms. This pseudopolypoid form of Crohn's disease poses, in addition to diagnostic problems, pathogenic questions, integrating these findings within the context of nonspecific reactions of the colon, secondary to an ulcerating process which may be specific.


[Pseudo-membranous colitis. 10 cases (author's transl)].

Pseudo-membranous colitis may develop after treatment with antibiotics, and in particular lincomycin a, d clindamycin. A "thumbprint" appearance of lacunae 2 to 4 mm in diameter, in substraction in relation to the wall of the colon, diffuse involvement of the colon and the regression of these signs when antibiotics are stopped are the typical radiological signs of this disorder.


[Broncho-alveolar spread in a case of juvenile laryngeal papillomatosis (author's transl)].

The authors report the case of a 30-year-old man suffering from juvenile laryngeal papillomatosis, recurrent since the age of 4. 23 years later, multiple round opacities were found in the lungs, progressing slowly to excavation. Bronchoscopy with broncho-aspiration provided histological confirmation of the diagnosis of broncho-alveolar spread of the papillomatosis, made on the basis of plain films and tomography.


[Solitary azygos prolongation (author's transl)].

Azygos prolongation of the inferior vena cava is a congenital abnormality which is normally associated with a congenital cardiac lesion, abnormalities of the inferior caval system and, in some instances, abdominal heterotaxia. The authors report here a case which is exceptional in the sense that the azygos prolongation was isolated. Further radiological studies are essential in order to make the diagnosis following the discovery of a right-sided laterotracheal opacity on a plain chest film. Only five other cases were found in the literature.


[Post-traumatic stenosis of the small intestine with double contrast radiological study after duodenal intubation. One case (author's transl)].

The authors present a clinical case of post-traumatic stenosis of the small intestine. The improvement in the quality of radiological diagnosis by the use of double contrast study of the small bowel after duodenal intubation is emphasised. On the basis of this case, together with a review of the literature, they review the various problems of diagnosis, physiopathology and histology which may be posed by these stenoses, which it would seem possible to integrate into a wider physiopathological group: ischaemic stenoses of the digestive tract.


[Cystic pneumatosis affecting the sigmoid. Information provided by colonic mucography (double contrast enema) and endoscopy. One case; diagnostic significance of the "puzzle" appearance (author's transl)].

On the basis of one case of colonic sub-mucosal cystic pneumatosis explored by double contrast enema, the authors emphasise the pathognomic diagnostic value of the "puzzle" appearance. This appearance is made by precise adaptation of the opaque colonic mucosa depressed in the form of a "cupola" over the intraparietal gas bubble which results in the deformity. Endoscopy failed to reveal the disorder in the case reported here.


[Congenital cystic dilatation of biliary tract (author's transl)].

The congenital cystic dilatation of biliary tract is un frequent affection and there are many types described (classification of Alonso Lej). The authors present the observation of a little girl of 12 years who presented a complete cystic dilatation ob biliary tract, diagnosed before the operation by intravenous biligraphy. This association of intra and extra hepatic cystic dilatation has been described in 1964 by Arthur and Stuart, and the diagnosis is to be done by intraveinous biligraphy in 30% of cases.


The effect of single intracisternal dry cow administration of staphylococcal antigens and antibiotics on the incidence of staphylococcal bovine mastitis.

The incidence of staphylococcal mastitis was investigated in 3 large commercial Friesland herds before and after the single intracisternal administration, during the dry-period, of 1 of 4 formulations containing staphylococcal antigens, antibiotics and base alone or in combination. Results suggest that the instillation of vaccine alone and vaccine plus antibiotics into fully involuted quarters very significantly reduced the incidence of staphylococcal mastitis in the subsequent lactation. Compared with antibiotics and base, each administered alone, the vaccine reduced the number of infected quarters in the subsequent lactation by 70,52% and 79,52% respectively, whereas the corresponding values for vaccine plus antibiotics were 62,22% and 71,22% respectively. The difference in results between vaccine alone and vaccine plus antibiotics is statistically insignificant, as is the difference between the results achieved by antiobiotics and base alone. The vaccine plus antibiotics is thought to possess combined therapeutic-preventive activity. The investigation showed, however, that vaccine plus antibiotics consistently protected mastitis negative quarters against new attacks of staphylococcal mastitis during the subsequent lactation period about 1,43, 4,00 and 5,32 times more effectively than did vaccine, antibiotics and base used individually.


The results of a mastitis awareness scheme in dairy herds in Natal and East Griqualand.

Over a period of 3 years some 314 widely distributed producers of fresh milk were made aware of their mastitis situation by regularly reporting the results of electronic determination of somatic cell counts in their bulked herd milk. These reports were preceded by information on the significance of high cell counts and followed by information relative to herd control of mastitis. The data are summarized in 2 figures and 1 table. Statistical analysis reflects a steady and significant improvement in the overall cell count picture over the duration of the programme. No differences could be established between counts on milk delivered in bulk and that delivered in cans. Regional differences existed. Of the herds in which the cell content was reduced to below 500 000/ml, 65% reported an increase in production and a decrease in the incidence of clinical mastitis. In the herds where no decrease in cell content was effected, only 20% reported an increase in production and 30% a reduction of clinical mastitis. Whatever the case, the consumers of the milk benefitted in receiving aesthetically more acceptable milk.


[Examination for infertility in cattle (author's transl)].

In order to evaluate clinically recognisable manifestations while undertaking examinations for fertility in cattle it is necessary to take cognizance of the physiological events taking place during the puerperium. The frequently incorrect diagnoses of cystic degeneration of the ovaries during this period can be avoided if the mechanisms controlling ovarian activity are properly understood. The close interaction between the ovaries, the hypothalamus, the hypophysis and adrenals as well as the luteolytic mechanism controlling ovarian activity is discussed. Attention is focussed on the effect of various pathogens on the endometrium, the influence of nutrition on the reproductive cycle and the consequent ovarian changes. The necessity to institute fertility examinations on a herd basis is stressed rather than attempts at treating the individual animal which, according to the owner, requires veterinary attention. By doing so a much more satisfactory service can be rendered. The existence of competent diagnostic centres, where the practitioner can obtain a metabolic or infection profile, is absolutely essential when fertility examinations on a herd basis are considered.


Blood levels of oxytetracycline in dogs after oral administration.

Blood levels of oxytetracycline in dogs were determined by a spectrofluorometric method. Doses of 10, 50 and 100 mg/kg body mass were administered as single doses per os. A single dose of 100 mg/kg body mass gave adequate blood levels and the 10 mg dose was inadequate. When doses of 10 and 50 mg/kg body mass respectively were repeated after 12 hours the higher dose gave adequate blood levels. Blood levels after dosing with 3 different commercial products containing oxytetracycline proved the non-equivalence of these products.


Langerhans cells in the epithelium of the bovine forestomach: their role in the primary immune response.

Dendritic, migratory, lymphoid cells identical to the Langerhans cells of the epidermis, have been found in the epithelium of the bovine forestomach. They also possess the characteristic Langerhans cell granules. It can be assumed that these epithelial lymphocytes, (or Langerhans cells) as has been reported for the epidermal Langerhans cells, are antigen detectors and therefore form the first line of defence in the general immunological response of the body. The author suggests that the Langerhans cells of the forestomach be named epithelial lymphocytes. The existence of Langerhans cell granules has not yet been reported in the epithelial lymphocytes of the true stomach, intestines and respiratory epithelium.


A suspected lysosomal storage disease in Abyssinian cats. Part I: genetic, clinical and clinical pathological aspects.

The genetic, clinical and clinical pathological findings of a neurological syndrome in Abyssinian kittens are described. The findings are compared with similar cases in the literature and a tentative diagnosis of a lysosomal storage disease is proposed.


A suspected lysosomal storage disease in Abyssinian cats. Part II: histopathological and ultrastructural aspects.

The histopathological and ultrastructural findings in the central nervous system and lymphoid tissue of Abyssinian kittens suffering from a disease which was clinically characterised by neurological disturbances, are described. The lesions were vacuolisation of neurones and macrophages with light microscopy and lamellated membranous cytoplasmic bodies, initially in lysosomes with electron microscopy. Irregularly shaped membrane-bound bodies with an amorphous substance were eventually formed in the cytoplasm of affected cells. It is considered that this is a lysosomal storage disease.


Ganskweek (Lasiospermum bipinnatum) poisoning in cattle.

An outbreak of ganskweek poisoning in a herd of 93 cattle on a farm in the Graaff-Reinet district of the Cape Province is described. Five animals died and at least 16 others were affected. Clinical signs included nervous symptoms (intractability, wildness, aggressiveness), icterus, melaena, abdominal pain and photosensitisation. The most prominent lesions present in the one animal autopsied were a severe hepatopathy and haemorrhagic tendencies.


A congenital oesophagotracheal fistula in a two-year-old dog.

A congenital oesophagotracheal fistula in a two-year-old dog is reported. An account is given of the clinical symptoms, radiographic appearance, the supportive therapy, surgical correction and the post mortem findings.


Bovine fluid therapy.

The paper emphasizes that fluids are generally given to cattle in insufficient quantities. Estimation of the state of hydration and calculation of requirements for replacement and maintenance for 24h is essential. Administration routes of choice are discussed. Acid-base balance, the relative importance of bicarbonate, K, Na, Ca, glucose and blood and precautions regarding typical South African conditions are discussed. Several examples of cases are presented, as are tables and formulae for calculation and replacement of fluid. The paper is essentially a practical guide for clinicians.


Salmonellae in Rhodesia: sources and serotypes of some isolates from abattoirs, domestic animals, birds and man.

Sources and serotypes of some salmonellae isolated from abattoirs, domestic animals, birds and man are given. At least 72 serotypes have been identified from 1273 isolations from abattoirs, animals and birds, and from 7 137 isolations from man. The sources and serotypes of these isolations are discussed and some suggestions concerning the epidemiology of Salmonella in Rhodesia are made.


Common canine dermatoses.

Refractory canine skin disorders from a large percentage of the cases referred to the Department of Medicine, Faculty of Veterinary Science, University of Pretoria. Included in these conditions are allergic skin diseases, primary pyoderma, generalised pustular demodicosis, endocrine alopecia, dermatomycosis, seborrhoea, acral pruritic nodule and nasal solar dermatitis. These conditions are discussed with emphasis on aetiology, pathogenesis, diagnosis and treatment. Thirteen colour plates illustrate the classical appearance of the dermatoses described.


Fertility and infertility problems in sows.

The overriding economic importance of reproductive efficiency to successful pig production makes it necessary to collect and analyse performance records for the diagnosis and control of reproductive failure. Recently published production standards from the United Kingdom are related to the results obtained from 68 herds in the National Pig Health Scheme. It is concluded that more attention to the managerial aspects of weaning and rebreeding will do much to improve farrowing frequency.


Surgical correction of premature closure of the ulnar growth plate in the dog.

Successful correction of anterior bowing of the foreleg and severe lateral carpal valgus following on premature closure of the ulnar growth plate in a month old Great Dane bitch is described. The procedure involved stapling the radius across the distal growth plate and section of the ulna.


Mechanisms of voltage transients during current clamp in Necturus gallbladder.

Microelectrode techniques were employed to study the mechanisms of the transepithelial voltage transients (deltaVms) observed during transmural current clamps in the isolated Necturus gallbladder. The results indicate that: a) part of deltaVms is due to a transepithelial resistance change (deltaRt), and part to a tissue emf change. b) deltaRt is entirely caused by changes of the resistance of the paracellular pathway. At all current densities employed, the measured changes are probably due to changes in both fluid conductivity and width of the lateral intercellular spaces. At high currents, in addition to the effects on the lateral spaces, the resistance of other elements of the pathway (probably the limiting junction) drops, regardless of the direction of the current. c) The magnitude and polarity of the deltaRt-independent transepithelial and cell membrane potential transients indicate that the largest emf change takes place at the basolateral membrane (deltaEb), with smaller changes at the luminal membrane (deltaEa) and the paracellular (shunt) pathway (deltaEs). It is shown that two-thirds of the transient are caused by deltaEs, and one-third by delta(Eb--Ea). deltaEs can be explained by a diffusion potential generated by a current-dependent NaCl concentration gradient across the tissue. deltaEa and deltaEb are caused by [K] changes, mainly at the unstirred layer in contact with the basolateral membrane.


Electrical noise from lipid bilayer membranes in the presence of hydrophobic ions.

In the presence of the hydrophobic ion dipicrylamine, lipid bilayer membranes exhibit a characteristic type of noise spectrum which is different from other forms of noise described so far. The spectral density of current noise measured in zero voltage increases in proportion to the square of frequency at low frequencies and becomes constant at high frequencies. The observed form of the noise spectrum can be interpreted on the basis of a transport model for hydrophobic ions in which it is assumed that the ions are adsorbed in potential-energy minima at either membrane surface and are able to cross the central energy barrier by thermal activation. Accordingly, current-noise results from random fluctuations in the number of ions jumping over the barrier from right to left and from left to right. On the basis of this model the rate constant ki for the translocation of the hydrophobic ion across the barrier, as well as the mean surface concentration Nt of adsorbed ions may be calculated from the observed spectral intensity of current noise. The values of ki obtained in this way closely agree with the results of previous relaxation experiments. A similar, although less quantitative, agreement is also found for the surface concentration Nt.


Freeze-fracture for scanning electron microscopy.

Two different freeze-fracture methods are explored for preparation of biological material for scanning electron microscopy. In the simpler method the tissues are first fixed and dehydrated. They are then frozen and fractured, and after thawing, critical-point dried. This method has already been used in a number of studies of animal tissues (heart, liver, kidney). It is applied here to the examination of plant material (leaf mesophyll cells). In the second method tissues, or cells, are first infiltrated with cryoprotectant (dimethylsulphoxide) then frozen and fractured, and not fixed until after thawing. The fixed tissues are finally dehydrated and critical-point dried. This method also has previously been used in the study of animal tissues, and is applied here to carrot protoplasts, chicken erythrocytes, and leaf mesophyll cells.


A device for dark field microphotography at low magnifications.

A simple illumination system is described that can be easily adapted to a laboratory stereomicroscope allowing for low power high contrast dark field surveying. The system uses commercially available fibre optic lamps, standard bright field objectives and produces a large, evenly illuminated field suitable for photography.


Cyanamide mediated syntheses under plausible primitive earth conditions. II. The polymerization of deoxythymidine 5'-triphosphate.

When an aqueous solution (pH 7.0) of 3H deoxythymidine 5'-triphosphate, deoxythymidine 5'-phosphate, 4-amino-5-imidazolecarboxamide, cyanamide and ammonium chloride was dried and heated at 60 degrees C for 18 h, oligomers were obtained in a yield of approximately 80%. After the chemical degradation of any pyrophosphate bonds present in these oligomers, linear polynucleotides of up to 7-8 units in length were isolated by DEAE cellulose column chromatography and identified by enzymatic digestion procedures. The di- and trinucleotide fractions were degraded 87% and 100% by snake venom phosphodiesterase and 39% and 9% by spleen phosphodiesterase. This synthesis of deoxythymidine oligonucleotides was conducted under potentially prebiotic conditions and may offer a possible method for the synthesis of deoxyoligonucleotides on the primitive Earth.


Cyanamide mediated syntheses under plausible primitive earth conditions. III. Synthesis of peptides.

Peptides were formed in yields of 5%, 17% and 66%, respectively, when aqueous solutions of glycine, isoleucine or phenylalanine were dried and heated for 24 h at 90 degrees C with adenosine 5'-triphosphate, 4-amino-5-imidazolecarboxamide and cyanamide. Glycine and L-phenylalanine produced mixtures of di-, tri- and tetrapeptides, while L-isoleucine gave only the dipeptide in detectable quantities. The dipeptides of L-isoleucine and L-phenylalanine were identified by mass spectrometry and enzymatic and enzymatic degradation.


Cyanamide mediated syntheses under plausible primitive earth conditions. IV. The synthesis of acylglycerols.

The synthesis of palmitoylglycerols in good yields occurs when a solution of glycerol, ammonium palmitate, cyanamide and imidazole is dried and heated at ambient humidity at temperatures ranging from 60 degrees--100 degrees C for 16 h. Much less product is formed in the absence of either or both cyanamide or imidazole. This work suggests that acylglycerols could have been synthesized on the primitive Earth under plausible prebiotic conditions which were similar but not identical to those which have been shown to condense deoxynucleotides into oligodeoxynucleotides and amino acids into peptides.


Evaluation of the non-randomness of protein compositions.

A method is described for assessing the non-randomness of protein compositions, based on the chi-squared statistic for the differences between the observed numbers of residues of each type and the numbers expected for a random distribution of codons. The analysis indicates that changes in at least 30% of the residues in natural proteins are selected against.


Partitioning of amino acids and nucleotides between water and micellar hexadecyltrimethylammonium halides. The prebiotic significance of cationic surfaces.

Using quantitative gel filtration techniques partition coefficients, Kp-values, have been determined between aqueous cationic micellar hexadecyltrimethylammonium bromide, CTAB, and several biomonomer. Kp-values for 5'-adenylic acid, 5'-cytidylic acid, 5'-guanylic acid, 5'-uridylic acid and 5'-thymidylic acid are 1,400 +/- 150. Nucleotides bind to CTAB micelles effectively, but nonselectively. Conversely, the binding of tRNAs to micellar CTAB is selective. Kp-values for glutamic acid II, tyrosine and phenylalanine tRNAs (in 1.0MNaCl) are 520, 3,100 and 5,600, respectively. Kp-values for the binding of alanine, arginine, aspartic acid, glutamic acid, glycine, histidine, phenylalanine, serine, threonine and tryptophan to micellar CTAB are less than 8. Conversion of unitless Kp-values for the binding of amino acids, nucleotides and nucleosides to both anionic and cationic micelles, to K (in 1/g) values allows the comparison of clays and micelles as prebiotic concentrating media. Using correlations between surface densities of the biomonomers and their binding constants, it is shown that aqueous micelles (at pH = 8) are a better concentrating media than are clays.


Ribonucleotide reduction and the possible role of cobalamin in evolution.

The biological pathways of ribonucleotide reduction are briefly reviewed. The hypothesis is presented that reduction of ribonucleoside triphosphates to their deoxynucleotide analogs through the mediation of vitamin B12 or a similar corrinoid preceded and was necessary for the subsequent development of a DNA-type genome. There are two known biological systems for ribonucleotide reduction: (1) The ribonucleoside diphosphate reduction system which utilizes a nonheme iron ribonucleotide reductase enzyme, thioredoxin and its reductase, and NADPH. This enzyme complex is found in most bacteria, some higher organisms, and in all animals. (2) The ribonucleoside triphosphate reduction system which utilizes adenosyl cobalamin, ribonucleotide reductase and either thioredoxin or a disulfhydryl compound. The cobalamin-dependent reductase is restricted to a few species of bacteria and blue-gree algae. This system is considered more primitive than the iron reductase one based on their differences in distribution, components, and products.


Effect of respiratory infection on the elution of benzo[a]pyrene from carbon particles in the respiratory tract of mice.

The effect of respiratory infection by PR8 influenza virus on the elution of bnezo[a]pyrene (BaP) from carbon particles in the respiratory tract of mice was studied. In mice, this virus produces, among other pheneomena, a proteinaceous effusion and mixed cellular exudate in the alveolar parenchyma during the acute phase of infection. If BaP-coated carbon particles are introduced into the respiratory tract during the acute stage of infection, the rate of BaP elution from the carbon particles is increased. When BaP-coated carbon particles were instilled in the respiratory tract either 1 wk before or 2 wk after the acute stage of infection, the BaP elution rate from carbon particles were similar to that in uninfected animals.


Pharmacokinetics and distribution of styrene monomer in rats after intravenous administration.

An interest in the pharmacokinetics of styrene monomer in the rat, arising from the presence of the monomer in the industrial work place and in foods, necessitated an investigation of the dose dependency of the kinetics of styrene monomer when administered by the iv route. A rapid distribution of the monomer to the major organs was observed, and all of the rate coefficients describing the rates of distribution and elimination decreased with increasing dose. No change in the apparent volume of distribution with dose was observed. Some evidence for the involvement of saturable metabolic pathways was obtained.


Rapid and accurate determination of the median lethal dose (LD50) and its error with a small computer.

A program for a small digital computer was developed to calculate the median lethal dose (LD50) and its errors. The algorithm employed in the program was based on a method described by Bliss. Modifications introduced by Finney are also discussed. The results indicate a high degree of accuracy compared with calculations performed by Bliss. The accuracy and speed of calculation exceeded those possible with simplified and graphic methods. The data and results for four toxic compounds are presented.


Effect of butylated hydroxytoluene and other antioxidants on mouse lung metabolism.

Toxic doses of butylated hydroxytoluene (BHT), a phenolic antioxidant commonly used as a food additive, are known to produce lung damage. In this study, 3 days after a single ip injection of 62.5, 215, or 500 mg/kg BHT in mice there was a dose-dependent increase in lung weight. This concentration dependence with injected BHT was accompanied by increases in lung DNA and nonprotein sulfhydryl levels and in whole lung tissue enzyme activities of glutathione (GSH) peroxidase, GSH reductase, glucose-6-phosphate dehydrogenase, and superoxide dismutase. The increased enzyme activities are considered to correspond to inflammatory and proliferative pulmonary changes resulting from acute lung cell injury and necrosis, which have been described previously, and cannot be construed as evidence for a primary oxidant-induced pulmonary lesion. The mechanism of BHT-induced lung changes may not be related to the antioxidant property of BHT, since vitamin E, n-propyl gallate, ethoxyquin, N,N'-p-phenylenediamine, and the structurally similar compound, butylated hydroxyanisole did not appear to produce the gross anatomical or biochemical lung changes observed with BHT.


Human safety data collection and evaluation for the approval of new animal drugs.

Before a new drug is approved for use in food-producing animals, data are required which demonstrate that food derived from the animal does not contain unsafe residues. Also, an analytical method for residues must be provided which is practicable for government surveillance and enforcement activities. Residue information is derived by using radiolabeled drugs to study metabolism in the animal for which the drug is intended. Residues in the edible tissues are characterized, and the amount of residues and their rates of depletion from the different tissues after cessation of drug treatment are determined. Bioassays with laboratory animals are used to study the toxicity of the drug and its important metabolites and to establish tolerance limitations. From this information, the conditions for the analytical method are established--that is, the compound(s) measured (the marker), the tissue (target tissue) monitored to ensure control of "total residue", and the required sensitivity. The method is subjected to validation in government laboratories and must meet the Food and Drug Administration's standards of precision, accuracy, specificity, and practicability. Finally, the method is used in simulated field trials to establish the required withdrawal time after drug treatment before the animals can be marketed for their milk or for slaughter for food.


Alopecia induced by inhalation exposure to phenyl glycidyl ether.

Rats and dogs were exposed to heated phenyl glycidyl ether (310 degrees C) vapor at average levels of 1.3, 5.0, and 11.8 ppm (v/v) for 6 hr/day, 5 days/wk, for 90 days. No adverse effects were observed in the dogs and rats other than alopecia in rats at the dose levels of 5.0 and 11.8 ppm. Microscopically, the skin lesions revealed slight acanthosis, hyperkeratosis, and occasional patchy parakeratosis in the epidermis. Follicular keratin plugs were observed with hyperkeratosis of epithelium in the hair follicles and sebaceous glands. Inflammatory reaction was mainly confined to the perifollicular region and affected the hair follicles, resulting in atrophy. The number of hair follicles in the resting stage appeared to increase. The hair shafts revealed impairment of keratinization and fragmentation. Extracted hairs showed an increase in the number of dystrophic follicles and constricted or broken hair shafts.


Neurological and behavioral effects of intracranial administration of mercuric chloride on rats.

Mercuric chloride was injected intracranially into the rat brain in the region of the fourth ventricle via the foramen magnum. Responses to a single treatment of 0.3 mg/kg HgCl2, 0.03 mg/kg HgCl2, or carrier solution were followed for 10 days. Changes in the rats' behavior and motor coordination were observed 24-48 hr after treatment with HgCl2. Underwater swimming and decreased grooming and feeding were characteristic of mercury-treated rats. Decreased balancing ability and crossing of hind limbs suggested altered motor coordination. Rats treated with mercury often exhibited decreased body temperature, matting of fur about the eyes and perineal region, apparent visual impairment, decreased body weight, and diarrhea.


Chromosomal aberrations in workers professionally exposed to lead.

Chromosomes in cultured lymphocytes from the following groups were analyzed: 16 workers from a smelting plant for storage batteriers in Lyon, France; 7 workers from a factory where tin dishes are made at Nerem, Belgium; and 20 controls. The choice of the workers was made on the basis of either elevated blood lead (Lyon) or elevated urinary delta-aminolevulinic acid (Nerem). An increased number of severe aberrations--rings and dicentrics--were detected in the persons from Lyon, whereas no such aberrations but an increased number of fragments were seen in those from Nerem.


Effects of DDE on experimentally poisoned free-tailed bats (Tadarida brasiliensis): lethal brain concentrations.

Adult female free-tailed bats (Tadarida brasiliensis) were collected at Bracken Cave, Texas, and shipped to the Patuxent Wildlife Research Center. Treated mealworms (Tenebrio molitor) containing 107 ppm DDE were fed to 17 bats; five other bats were fed untreated mealworms. After 40 days on dosage, during which one dosed bat was killed accidentally, four dosed bats were frozen and the remaining 17 were starved to death. The objective was to elevate brain levels of DDE to lethality and measure these concentrations. After the feeding period, dosed bats weighed less than controls. After starvation, the body condition of dosed bats was poorer than that of controls even though there was no difference in the amounts of carcass fat. During starvation, dosed bats lost weight faster than controls. Also, four dosed bats exhibited the prolonged tremoring that characterizes DDE poisoning. DDE increased in brains of starving bats as fat was metabolized. The estimated mean brain concentration of DDE diagnostic of death was 519 ppm with a range of 458-564 ppm. These values resemble diagnostic levels known for two species of passerine birds, but they exceed published levels for two free-tailed bats from Carlsbad Caverns, New Mexico.


Tumur induction by 7H-dibenzol[c,g] carbazole in the respiratory tract of Syrian hamsters.

The respiratory tract of male and female Syrian golden hamsters was treated intratracheally with 7H-dibenzo[c,g]carbazole (DBC), a tobacco smoke component. The carcinogen was given by multiple instillations at two dose levels. At the lower dose (9 mg), 35 of 46 hamsters (72%) developed respiratory tract tumors. The group receiving treatment at the higher dose level (30 mg) died earlier because of the toxicity of the compound. In this group, 15 of 45 animals (33%) had respiratory tract tumors. These occurred in the larynx, trachea, bronchi, and lungs, but predominated in the trachea and bronchi. Morphologically, most tumors were papillomas and squamous cell carcinomas. This study indicates the highly potent carcinogenic effect of DBC and that respiratory tumors can be induced in this model system without any carrier dust.


Fate of silvex following oral administration to humans.

The fate of silvex [2-(2,4,5-trichlorophenoxy)propionic acid] was defined in seven men and in one woman following oral administration of 1 mg/kg. No adverse effects were observed. Samples of blood plasma, urine, and feces were collected at designated time intervals through 168 hr. Plasma samples were analyzed for silvex only, while samples of urine and feces were analyzed for silvex, silvex conjugate(s), 2,4,5-trichlorophenol, and 2,4,5-trichlorophenol conjugate(s). Apparent first-order kinetics described the biphasic clearance of silvex from plasma and excretion in urine. The half-life values for clearance of silvex from plasma were 4.0 +/- 1.9 and 16.5 +/- 7.3 hr for the initial and terminal phases, respectively. Peak plasma levels of silvex occurred within 2-4 hr after dosage. Within 24 hr after administration, 65% of the administered dose had been excreted in urine. Silvex was excreted in urine as silvex and silvex conjugate(s). The half-life values for excretion of silvex per se in urine were 5.0 +/- 1.8 and 25.9 +/- 6.3 hr for the two phases, respectively. Small amounts (3.2% or less) of silvex and/or silvex conjugate(s) were eliminated in feces. Recovery of silvex and its conjugate(s) in urine and feces through 168 hr ranged from 66.6 to 95.1% of the administered dose, with a mean value and standard deviation of 80.3 +/- 10.5%. In humans, silvex is readily absorbed after ingestion and subsequently readily excreted, predominantly via the urine.


Metabolism of 17alpha-ethynylestradiol by intact liver parenchymal cells isolated from mouse and rat.

Liver parenchymal cells isolated by perfusion from female C3H/HeN-MTV+Nctr mice and Sprague-Dawley rats were incubated with [6,7-3H] 17alpha-ethynylestradiol (EE2). The incubates were individually fractionated into free steroid (organic phase), steroid conjugates (aqueous), and bound steroids (macromolecular pellet). The rat had significantly less total free radioactive steroid but significantly more total conjugated and irreversibly bound radioactivity than the mouse. However, when the metabolic conversion of EE2 was compared in the rat and the mouse on a cellular basis (metabolic clearance per 10(6) cells), the rat was found to be less efficient than the mouse. The two species were essentially equivalent in their covalent binding when expressed on a per 10(6) cell basis. Purification of the free radiolabeled steriods on LH-20 demonstrated the mouse to have the parent compound and on identifiable 2-OH-EE2 fraction. The rat had EE2 and an identifiable 2-methoxy-EE2 fraction. A major metabolite fraction for both species was very nonpolar and, although not identified, was found to be ethynylated as demonstrated by silver-sulfoethylcellulose chromatography. The conjugate fractions of the mouse were indicative of glucuronide conjugation, whereas the rat had additional conjugate fractions suggestive of sulfoconjugation.


A dominant lethal study in male rats after repeated exposures to vinyl chloride or vinylidene chloride.

Male CD rats were exposed 6 hr/day for 5 days/wk to 0, 50, 250, or 1,000 ppm of vinyl chloride or 55 ppm of vinylidene chloride. Starting on week 11 of exposure, these males were mated with untreated females. There was no evidence of either preimplantation loss or postimplanation loss in pregnant females that resulted from these matings. Consequently, it was concluded that these exposures did not produce germinal mutation, as manifested by a dominant lethal effect, in male rats.


Potential biological hazards of commercially available cleansers for dentures.

Thirteen representative denture cleansers were selected from among more than 32 retail products to be tested for potential hazard and toxicity to humans. Products were subjected to toxicological analyses by using the biological tests (acute oral toxicity in rats, eye and skin irritation in rabbits) specified in the Federal Hazardous Substances Act Regulations. All products were eye irritants with ranges from slight to severe. Three produced a primary skin irritation response (one was corrosive), while five of the denture cleansers produced oral LD50 values below 5 g/kg. Furthermore, a provisional upper gastrointestinal  irritancy test used in rabbits indicated that eight of the denture cleansers produced upper gastrointestinal irritation, which was, in general, dose-related.


Renal and testicular damage following dermal application of the flame retardant tris (2,3-dibromopropyl) phosphate.

Tris(2,3-dibromopropyl) phosphate (TRIS) was the most popular flame retardant chemical used in children's sleepwear. Acute toxicological data indicated that TRIS was low in toxicity. Since human exposure to TRIS-treated fabrics could occur for long periods of time, a subchronic study was undertaken to obtain additional information. The dermal application of TRIS (neat) at a dose of 1 ml/kg (2.27 g/kg) to the clipped backs of albino rabbits, once each week for 3 months, resulted in testicular atrophy and chronic interstitial nephritis in males. Females did not show any adverse effects.


Neurobehavioral effects of prenatal exposure to the organophosphate Diazinon in mice.

Pregnant mice were given to daily dose of 0, 0.18, or 9.0 mg Diazinon per kilogram body weight throughout gestation. Mothers of all dose groups gave birth to viable, overtly normal offspring. However, pups born to mothers receiving the higher dose of the organophosphate grew significantly slower than controls and remained significantly smaller at 1 month of age. Offspring of mothers receiving the lower dose apparently were unaffected, but systematic behavioral testing revealed subtle deviations from normal developmental ontogeny as shown by significant delays in the appearance of the contact placing reflex and of sexual maturity (descent of testes or vaginal opening). Mature offspring of mothers exposed to either dose of the pesticle displayed impaired endurance and coordination on rod cling and inclined plane tests of neuromuscular function. Offspring from the 9.0 mg/kg group, in addition, had slower running speeds in a Lashley III maze and less endurance in a swimming test. Brains obtained after sacrifice at 101 days of age revealed neuropathology in the forebrains of offspring born of mothers exposed to the higher dose. Despite functional impairments in offspring from the lower dose group, no corresponding brain pathology was observed by examination under the light microscope.


RNA release from isolated brain cell nuclei: influence of the postnatal cerebral development.

A method to measure the "in vitro" RNA release from rat brain cell nuclei was described. Nuclear RNA was prelabelled "in vivo" for 30 or 120 min. In the first case the released RNA was heterogeneous and its electrophoretic mobility was similar to that of cytoplasmic messenger RNAs; nuclei prelabelled for 120 min mostly released the two major species of ribosomal RNAs. The release of mRNAs from the nuclei increased during cerebral development while that of the ribosomal RNAs did not. The increased capacity of the nuclei to release "radidly labelled" RNA with age neither determined an increase of the polysomal population, nor seemed to be dependent on cytoplasmic macromolecules.


Topographical distribution of acetylcholinesterase and butyrylcholinesterase in the diencephalon and mesencephalon of the garden lizard (Calotes versicolor).

The present report incorporates the histochemical mapping of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) among the various nuclei and fiber tracts of the diencephalon and mesencephalon of Calotes veriscolor. The various nuclei, for both enzymes, present varying degrees of staining, ranging from negative nuclei, on the one hand, to mild and intense staining on the other hand. Almost all of the fiber tracts reveal intense activity in BChE preparations, while they demonstrate mild and moderate activities for AChE. The nature of the various nuclei in relation to enzymatic patterns is discussed.


The effect of gallamine triethiodide on the activity of gamma motor neurons in the acute spinal cat.

Gallamine triethiodide, a drug commonly used in neurophysiological experiments, causes statistically significant and inconsistent changes in the information-carrying capacity of trains of action potentials generated by members of a population of gamma motor neurons recorded from the same cat under the same conditions during the same time period.


A permanent plastic cannula for intraventricular injections into rat brain.

The construction and use of a permanent, implanted plastic camnula for intraventricular injections in rat brain is described. The cannula can be used in either acute or chronic experiments.


Membrane protein and glycoprotein composition of beef brain synaptic vesicles.

Synaptic vesicles were isolated from adult bovine cortical gray matter by differential centrifugation and membrane filtration of a hypoosmotically lysed crude mitochondrial fraction. Vesicle preparations were analyzed for purity by electron microscopy and enzyme assays. Polyacrylamide gel electrophoresis of SDS-solubilized and 2-mercaptoethanol-reduced vesicle membrane proteins revealed 4 major proteins with molecular weights ranging from 17,000 to 60,000, and about 10 minor proteins with molecular weights up to 170,000. The protein profile of the Triton X-100-extracted vesicle membranes was less complex, with 1 major protein and 5 minor bands. The major protein of the Triton extract was identified as a glycoprotein with a molecular weight of 45,000. Two additional minor PAS-positive bands were seen, with molecular weights of 78,000 and 95,000.


Pineal-induced alterations in reproductive function and pituitary prolactin in the female rat: the effects of bilateral superior cervical ganglionectomy and nervi conarii transection.

The reproductive organs of female rats subjected to blinding and and anosmia were hypotrophic while pituitary prolactin stores were markedly depressed in these animals. All of the effects of dual sensory deprivation were reversed by either superior cervical ganglionectomy or nervi conarii transection. It was concluded that both of these surgical procedures were as effective as pinealectomy in reversing the pineal-induced alterations in the reproductive physiology of the blind-anosmic female rat.


Response properties of cells in the dorsal lateral geniculate nucleus of the albino rat.

The response patterns of cells in the dorsal lateral geniculate nucleus of the albino rat were studied in order to examine the functional organization of the lateral geniculate nucleus. Both photic stimulation and electrical stimulation of the optic tract were used to activate single units in the lateral geniculate nuclei. Three different types of response patterns were found for principal cells, while interneurons all had similar response patterns. The first class of principal cells, E-S cells, responded to stimulation with a period of excitation, followed by a period when activity was suppressed. A second class of cells, S cells, responded to photic stimulation with an initial period when activity was suppressed. The final class of cells, E cells, responded with a period of excitation followed by a return to spontaneous rates of firing. The response patterns of E cells suggest that this type of principal neuron does not receive feedback inhibition of the type proposed in previous models of the lateral geniculate nuclei. Based on these and other observations, a new model of the functional organization of the lateral geniculate nuclei is proposed.