Sea-blue histiocytes and sural nerve in neurovisceral storage disorder with vertical ophthalmoplegia.

Ultrastructural investigation of bone marrow histiocytes in neurovisceral storage disorder associated with vertical ophthalmoplegia revealed 3 types of cytosomes: (1) lamellar cytosomes; (2) larger cytosomes composed of lamellar fragments and a granular component; and (3) large irregular cytosomes with amorphous and granular portions, often including fingerprint profiles--in some of these, lysosome-like bodies were numerous. The lamellar cytosomes corresponded to vacuoles seen by light microscopy. The Type 2 and 3 cytosomes were the ultrastructural substract of Wright-Giemsa stained blue granules. Histiocytes having a predominance of Type 2 cytosomes in a cytoplasm rich in free ribosomes had the appearance of sea-blue histiocytes at the light-microscopic level. Transformed Type 1 cytostomes served as building blocks for Type 2 and 3 cytosomes. In the sural nerve, Schwann cells and endoneurial fibroblasts accumulated autofluorescent lipopigment but no lamellar cytosomes or their fragments were found on electron-microscopic examination. Ultrastructure of sea-blue histiocytes in this disease differed from that observed in some other diseases.


Electron-microscopic, cytochemical and biochemical studies of acetylcholinesterase and butyrylcholinesterase activity in muscle of dystrophic mice.

We have studied extrajunctional muscle of control and dystrophic mice by electron microscopic-cytochemistry and radiometric assay. We have found both a soluble and particulate AChE activity, which is similar proportionally in control and dystrophic muscle. The particulate AChE activity is probably due to the enzyme localized in the sarcotubular system. These sites are more numerous in muscle adjacent to the motor end-plant than in distally located extrajunctional muscle, and are increased markedly in the dystrophic mouse. Myoblasts and small muscle fibers in the dystrophic mouse also have AChE activity in the reticulum similar to fetal muscle. The soluble AChE activity identified radiometrically may represent those sites exhibiting random cytochemical end-product, such as some muscle nuclei, satellite cells, myogenic mononuclear cells in the connective tissue, and degenerating axonal boutons no longer associated with junctional folds of muscle. Enzyme activity is present in degenerating fibers, but it is randomly dispersed in the sarcoplasm rather than membrane-bound. AChE activity has not been found in debris of completely necrotic muscle. BuChE activity is higher and the number of BuChE-active sites in the sarcotubular system adjacent to the motor end-plates is greater in dystrophic muscle than in control muscle.


[Ultrastructural study of a chordoma].

An ultrastructural study of a case of sacral chordoma is reported. The cell type was monomorphic. The epithelial nature and the secretory function of the tumour cells was obvious in view of their content of desmosomes and the presence of mucopolysaccharide in the ergastoplasm and in the extracellular space. Because of the lack of intracytoplasmic vacuoles in the case reported, the authors doubt the individuality of the so-called "giant physaliphorous cell". The authors consider that the vacuolar appearance of the tumour cells is due to cytoplasmic invaginations caused by the enlarged extracellular space containing acid mucopolysaccharides or by processes of histiocytes containing the same material.


Effect of a new vasodilator (flunarizine) on the cerebral circulation.

In order to clarify the effects of flunarizine, a newly-synthesized derivative of piperazine on cerebral circulation and metabolism, cerebrocortical oxygen tension, carbon dioxide tension and cerebrocortical blood flow were continuously recorded, along with a simultaneous monitoring of arterial blood pressure in 11 cats. Maximal changes in cerebrocortical oxygen tension induced by intravenous administration of flunarizine (0.6-1.0 mg/kg) were compared with those of papaverine hydrochloride (1 mg/kg). Flunarizine caused increases in cerebrocortical oxygen tension as well as cerebrocortical blood flow and a decrease in cerebrocortical carbon dioxide tension despite a fall in blood pressure, indicating an increase of cerebral blood flow presumably due to cerebral vasodilatation. Since the increase of cerebrocortical oxygen tension induced by flunarizine was comparable to that induced by papaverine, it was concluded that flunarizine appears to be a potent vasodilator of cerebral vessels.


Serum factors influencing creatine phosphokinase. In vitro studies using diffusates.

In vitro studies with diffusates obtained following dialysis of serum samples have enabled us to confirm the presence of inhibiting and activating factors influencing CPK activity. Activating factors are commonly found in many neuromuscular disorders like Duchenne muscular dystrophy (DMD), spinal muscular atrophy and hypothyroid neuromyopathy, and inhibiting factors in dermatomyositis. These findings are further elaborated during serial serum CPK studies after EMG in 3 cases of neurogenic atrophy and 1 case of DMD. The in vivo inhibitory and activating influence of serum factor(s) at 96 and 160 hr respectively after EMG was confirmed by in vitro studies with the diffusates of these serum samples. The functional variations of these diffusates are shown to be related to differences in the composition of these diffusates suggested by paper chromatography.


Myelination of brain in experimental hypothyroidism. An electron-microscopic and biochemical study of purified myelin isolates.

Myelin development has been studied in the neonatally hypothyroid rat brain by isolation and characterization of purified myelin preparations. The hormone deficiency results in a suppression of compact myelin formation and the persistence of a lighter possibly pro-myelin fraction. The appearance of myelin basic protein was markedly delayed in the hormone-deficient animals and this effect on the basic protein moiety may be responsible for the delayed myelinogenesis.


Leucocyte proteinase activity and acute multiple sclerosis.

Increased leucocyte neutral proteinase activity is associated with an attack of multiple sclerosis. Raised neutral proteinase is found in other diseases with rapid destruction of neural tissues. Increased enzyme activity may be responsible for removing antigenic protein from the blood.


Correlation between regional cerebral blood flow and EEG frequency in the contralateral hemisphere in acute cerebral infarction.

The relationship between the rCBF and the electroencephalographic (EEG) frequency was investigated in the contralateral hemisphere of 22 patients with acute cerebral infarction. Reduced rCBF was observed in all patients studied. The degree of rCBF reduction was mild, moderate, or severe and ranged between 6 and 80% from the lowest age-matched normal values obtained in our laboratory. The frequency indices remained within normal limits (mean - 10.4 Hz) in 16 patients. Slower frequencies (mean - 6.3 Hz) were recorded in 6 patients. No correlation was found between the two parameters (P = 0.89). Both the EEG frequency and the rCBF are known to be closely related to the cerebral metabolic rate. The observed rCBF depression without concomitant changes in the EEG frequency raises the question of the role of globally-reduced cerebral metabolism as the cause of rCBF reduction in the noninfarcted hemisphere in stroke patients. Our findings constitute additional evidence that the contralateral hemisphere is involved in the haemodynamic changes occurring in acute cerebral infarction.


Effect of cortisol on the excitability of limbic structures of the brain in freely moving rats.

The effects of cortisol on the excitability of the dorsal hippocampus, septum, hypothalamus and the pontine reticular formation in unrestrained, unanesthetized rats with permanently-implanted electrodes were investigated. The hormone produced a slowing in the spontaneous activity in these regions. The stimulation of the septum, hypothalamus and reticular formation had no appreciable influence on the local or propagated electrical activity of the brain after cortisol injection; however in 14 out of 29 experiments hippocampal stimulation with the same voltages as before cortisol administration, induced generalized convulsive activity. The attacks consisted of high-voltage spikes and slow-wave activity and were followed by a post-seizure exhaustion in the hippocampus. In half of the rats behavioral convulsions also appeared. The convulsive effects of cortisol on the brain are briefly reviewed and the specificity of hippocampal involvement in the present experiments is emphasized. The possible significance of the present findings in relation to the feedback of glucocorticoids on the brain, in the regulation of ACTH secretion, is discussed. The experiments described may also contribute to our understanding of the mechanisms of the convulsive effects of cortisol on the brain.


Virus infections in infant mice causing persistent impairment of turnover of brain catecholamines.

Newborn mice were inoculated with attenuated Coxsackie type B4 virus. Three-to-4-day old mice were infected with yellow fever virus vaccine. A number of mice survived the acute infections. Some of these demonstrated residual neurological symptoms, some showed recovery from symptoms while others survived the infection without revealing symptoms of disease. Determinations of dopamine, noradrenaline, 5-hydroxytryptamine, homovanillic acid and 5-hydroxyindoleacetic acid in the inoculated brains indicated an imparied turnover of neurotransmitters. Subnormal concentrations of catecholamines and homovanillic acid were encountered in the acutely-infected mice as well as among the survivors. Failure to synthesize catecholamines was observed not only in mice demonstrating symptoms of disease or in animals which recovered from their infection but also among a proportion of the mice which never demonstrated neurological symptoms. In contrast, 6-week-old Swiss albino mice infected with West Nile virus showed no effect on the turnover of brain monoamines either in acutely infected mice or in animals which survived the acute infection. Herpes simplex virus infection of 3-week-old mice induced during the acute infection an increased release of neurotransmitters. When these mice were "cured" of the infection by increasing the environmental temperature the elevated turnover of monoamine metabolism was normalized. Two months later there were no differences in concentrations of catecholamines or homovanillic acid between infected animals or uninfected controls. Thus, persistent impairment of brain monoamine metabolism was induced in mice infected when very young. The possible importance of the observations, in particular the findings of an impaired turnover after subclinical infection, is discussed.


Intramedullary cysticercosis. Case report, literature review and comments on pathogenesis.

A 60-year-old woman developed progressive spastic crural paraplegia and global anesthesia and global anesthesia below T10, succumbing to urinary infection and bronchopneumonia 8 months after the onset of symptoms. At necropsy, the spinal cord was completely destroyed by a necrotic intramedullary cysticercus at T8. Six cysticerci were found in the brain. A review of the 17 published cases of intramedullary cysticercosis (including this one) showed this condition to be clinically indistinguishable from spinal cord tumours. The surgical prognosis was fair in 8 of 11 operated patients. The role of hematogenous and ventriculo-ependymal pathways in the pathogenesis of intramedullary cysticercosis was examined. The topographical distribution of intramedullary cysticerci (5 cervical, 12 thoracic, 2 lumbar, none sacral) was found to be statistically proportional to the blood flow to each of these regions; this favours the hematogenous route of infestation. The low spinal cord blood flow (100 times less than that to the brain), the type of vascularization of the cord (low calibre vessels under low pressure) and peculiarities of the cord tissue (such as its harder consistency) are all thought to be contributory factors accounting for the scarcity of intramedullary cysticerci. No evidence for an ependymal route of spread could be adduced.


Specificity of the clinical diagnosis of dementia.

The specificity of anatomo-clinical observations were investigated on 776 out of 982 consecutive persons hospitalized at the University Psychiatric Clinic of Geneva. Discriminant function analysis shows that most of the anatomical classes (no dementia, senile dementia, Alzheimerized senile dementia and Alzheimer's presenile dementia, vascular dementia, combined dementia nnd undefined form of encephalopathy) are at least partially separable (less than 50% overlap). On the basis of anatomical criteria, Alzheimer's presenile dementia is not separable from Alzheimerized senile dementia, and senile dementia is not separable from combined dementia. Differentiation between the anatomical classes is improved by a preliminary analysis based on clinical diagnosis. Senile plaques account for 43.4% of the total variation between the anatomical classes. The coefficient of agreement between anatomical and clinical diagnosis is 0.27, which is highly significant. The diagnosis of senile dementia has a poor specificity, while the diagnosis of senile Alzheimerized dementia has a better one. The diagnosis of combined dementia has to be reserved for cases with a similar intensity of vascular and degenerative changes. Alzheimer's presenile dementia has a distinct dominant hereditary pattern and must be considered a separate entity. The high specificity of the diagnosis of Alzheimer's presenile dementia makes it possible to conduct epidemiologic and genetic surveys based on clinical data.


"Stimulus generalization" between differentiated visual, auditory, and central stimuli.

Cats were trained to discriminate between two different repetition rates of flicker and of click. Both approach-approach and avoidance-avoidance discriminations were used. After substantial overtraining, transfer of frequency discrimination was initiated to stimulation of the reticular formation using bursts of electrical pulses at the same two repetition rates. Significant levels of discriminated performance were obtained in all cats very quickly, indicating good cross-modal transfer between the peripheral discriminanda and the central stimuli. The literature on stimulus generalization and cross-modal transfer is reviewed and the findings of this experiment are discussed in that context. Certain conditions are defined which, if satisfied, justify the interpretation that stimulus generalization or rapid cross-modal transfer indicate that facilitation of subsequent tasks in a training sequence can be attributed to mediation by a specific neuronal mechanism established by training on a previous task. The present experiment was designed in view of such criteria. The evidence of good cross-modal transfer is interpreted to mean that brain mechanisms storing memories about discriminations between visual or auditory stimuli with different repetition rates can be effectively activated by gross electrical stimuli at the same repetition rates. Conflict trials were then carried out in which flicker or click at either frequency was contradicted by concurrent RF stimuli at the other frequency. As the current level of RF stimuli was parametrically increased, it was found that the central stimuli achieved almost complete control over the behavioral outcome in most cases. Concurrent transfer of training, using a counterbalanced training sequence, was then carried out to stimulation of the visual cortex, lateral geniculate, medial geniculate, and the intralaminar nuclei of the thalamus. In each case, rapid transfer was displayed by at least one animal. Once performance to brain stimulation at a given repition rate was established, little change was observed when the fine structure of the stimulus was altered by changing parameters of the stimulus burst. These findings are interpreted as providing support for a statistical theory of memory, since they constitute evidence that previously learned discriminative behavior can readily be elicited by compelling large ensembles of neurons in various brain regions to discharge with particular temporal patterns. It is difficult to reconcile these results with theories which postulate that learning establishes new synaptic pathways in which discharge must occur for memories to be retrieved.


Visual receptive-field properties of cells in area 18 of cat's cerebral cortex before and after acute lesions in area 17.

1. Receptive-field properties of single neurons in cat's cortical area 18 were studied before and after partial bilateral lesions of area 17. 2. The majority of cells recorded from animals with intact visual cortex exhibited orientation selectivity, directional selectivity, and could be independently activated through either eye. All cells responded well to moving targets and nearly all of them exhibited broadly tuned preferences with respect to speed of the target. Over 45% of cells responded optimally or exclusively at very fast (above 50 degrees/s) speeds. 3. The majority of neurons recorded from animals with intact visual cortex responded weakly but clearly to appropriately oriented localized stationary stimuli flashed on and off. About one-third of the cells responded with mixed on-off discharges from all over their receptive field. In the receptive fields of 10% of cells, separate on- and off-discharge regions could be revealed. In the receptive fields of the remaining cells, only on- or only off-discharge regions could be revealed. 4. The majority of neurons recorded after ablation of area 17 were orientation selective; 50% of the cells were also direction selective. All neurons responded well to moving targets; about 65% of them responded optimally or exclusively at very fast target speeds. 5. Destruction of the dorsolateral part of contralaterial area 17 and most of contralateral area 18 caused significant reduction in proportion of cells in area 18 which could be activated through either eye. 6. The majority of neurons recorded after ablation responded to appropriately oriented localized stationary stimuli flashed on and off. Cells with mixed on-off discharge regions all over the receptive field with separate on- and off-discharge regions and with only on- or only off-discharge regions were found. 7. It is concluded that the processing of afferent visual information in area 18 is, to a great extent, independent of the information carried to this area by associational fibers from cells of area 17.


Discharge patterns of cat pontine brain stem neurons during desynchronized sleep.

1. Discharge pattern has been characterized by autocorrelation analysis of stationary portions of extracellularly recorded discharge trains of cat pontine brain stem neurons during spontaneously occurring desynchronized sleep episodes. 2. Neurons localized to the area implicated in control of the desynchronized phase of sleep, the gigantocellular tegmental field (FTG), show the most phasic or clustered discharge pattern, as evinced by initial peaks in the autocorrelations. At the peak, the FTG population average discharge probability is 3 times that expected had the discharges been evenly distributed over time. The initial peak extends beyond a lag of 3 s, indicating runs of clustered discharge extending beyond this duration. Neurons in other reticular tegmental fields, the tegmental reticular nucleus and pontine gray, show a more sustained or tonic discharge pattern. 3. Discharge patterns of a given cell are consistent from one desynchronized sleep episode to the next; units with phasic discharge patterns remain phasic, and tonic patterns remain tonic. 4. There is a three-way correlation among FTG units recorded at sites with many giant cells, units with high discharge rate increases on transition to desynchronized sleep, and units with a markedly phasic discharge pattern. This implicates the giant cells as the source of both the distinctive discharge rate and pattern changes of neurons during desynchronized sleep. 5. Stereotyped, regular discharge patterns are not characteristic of FTG or other units, suggesting they are not pacemakers and that endogenous activation of pacemaker cells is unlikely to be a mechanism for generation of the marked discharge rate increases on transition to desynchronized sleep that are found in FTG units. The irregular, clustered discharge pattern of FTG is more compatible with generation of discharge rate increases through interaction with other cells. The markedly phasic discharge of FTG units is also consistent with a driving role in generation of the phasic electrophysiologic events of desynchronized sleep.


Neural control of circulation in Aplysia. III. Neurotransmitters.

In the abdominal ganglion of Aplysia californica, seven motoneurons have been described which modulate the myogenic heart beat and vasomotor tone (28). These neurons mediate their motor effects by chemical transmission. In this paper we have attempted to specify the transmitters of six of these motoneurons. We have 1) studied the effects of several common transmitters on the innervated structures and compared these effects with the effects of firing the motoneurons, 2) examined whether blocking agents influence similarly the effect of a putative transmitter applied to the innervated structure and the effect of firing a motoneuron, and 3) tested the capability of the motoneurons to synthesize the putative transmitters from precursors. The positive inotropic and chronotropic effects of firing the excitor motoneuron RB(HE) were mimicked by perfusion of the heart with serotonin at a low concentration. Cinanserin blocked both the effects of motoneuron excitation and serotonin perfusion. RB(HE) was also shown to synthesize [3H]serotonin from L-[3H]tryptophan injected directly into the cell body. The effects of firing the two LD(HI) heart-inhibitory motoneurons were mimicked by perfusion of the heart with acetylcholine. Benzoquinonium blocked the effects of the inhibitory motoneuron and acetylcholine perfusion. Perfusion with arecoline also inhibited the heart beat. Acetylcholine applied to the arteries mimicked the vasoconstriction caused by the LB(VC) motoneurons. Aortic constriction in response to activity in LB(VC) cells or to acetylcholine was blocked by hexamethonium and curare. The heart inhibitor and vasoconstrictor motoneurons synthesized [3H] acetylcholine from [3H] choline injected into their cell bodies. Thus, as in vertebrates, acetylcholine mediates inhibition to the heart. Unlike vertebrates, however, serotonin mediates excitation to the heart and acetylcholine mediates peripheral vasoconstriction.


Unit activity in posterior association cortex of cat.

1. "Association" neurons in the posterior middle suprasylvian gyrus of cat were found to be predominantly polysensory, with 82% of the units in the chloralose-anesthetized preparation responding to auditory, visual, and somatic stimuli. There was no evidence of response differentiation associated with cortical depth distribution. Most units responded with a short-latency response (median 35-60 ms) to all stimulus modalities, with the response to visual stimulation occurring at the shortest latency. Among polysensory cells, almost half responded with equal probability to auditory, visual, and somatic stimulation. The visual stimulus was the most potent for those cells responding with a higher probability to a single modality. Varying degrees of response complexity were noted in some cells in terms of changes in responsivity over time, discharge to stimulus offset, and inhibition of spontaneous activity. The unitary discharge was seen to occur on the negative peak and slope of the locally recorded evoked potential. When only the larger amplitude spikes were analyzed, most of the unitary activity occurred on the negative peak of the evoked potential. Almost half of trimodally responsive cells displayed similar phase relationships between unitary activity and evoked potentials for all three modalities. The absolute refractory period for most cells was from 200 to 300 ms, with relative refractory periods extending up to 30 s...


Latency of unit responses in cochlear nucleus determined in two different ways.

The latency revealed by poststimulus time histograms of the responses of single units in the cochlear nucleus to tone bursts was compared with the latency of the change in discharge frequency in response to small increments in the amplitude of the stimulus. The latter was derived on the basis of statistical signal analysis of the discharge pattern in response to tones amplitude modulated with pseudorandom noise. The "step response" of the system was computed by time integration of the cross covariance between modulation and spike density. The following observations can be made: 1. The latency of the responses to tone bursts always decreased with increasing sound intensity, whereas the latency of the step response was almost constant for intensities from immediately above threshold to the highest intensity used (60-70 dB above threshold). 2. In most units the latency revealed by the PST histogram of the responses to tone bursts approached the value of latency of the step response asymptotically. 3. In some units with longer latency, the latency of the response to tone bursts was many times greater than the latency of the step response, even at high sound intensities. 4. A histogram of latency values of the step response of the units studied showed narrow peaks at 2.8 and 4.7 ms. 5. On the basis of the present results it is concluded that the latency values of the step response represent the true sum of synaptic and axon dendritical propagation delay, whereas the latency of the responses to tone bursts also includes the temporal summation at the synaptic level.


Neuronal and glial activity during spreading depression in cerebral cortex of cat.

1. Extra- and intracellular potentials were recorded from neurons and glia during spreading depression (SD) in cerebral cortex of cats. The glial membrane depolarized during SD and the time course of depolarization was concurrent with the surface DC change of SD. The glial depolarization evoked by 20-Hz repetitive cortical stimulation disappeared during the negative DC shift of SD. Simultaneous recording of the extra- and intracellular potentials from a single glial cell with a coaxial microelectrode showed that the extracellular DC potential change was of opposite polarity to the glial intracellular potential, which suggests that the slow glial depolarization concurrent with SD is not the field potential. In contrast to glial cells, the neuronal burst discharges as well as the neuronal membrane depolarization associated with SD did not show a close relationship to SD: the neuronal membrane depolarization and discharge were frequently delayed by 10-3- s from the onset of the SD slow wave. Sometimes SD was observed without accompanying neuronal depolarization. The degree of neuronal depolarization was not always correlated with the amplitude of the negative wave of SD. 2. The effect of tetrodotoxin (TTX) on the negative DC potential of SD was examined. Simultaneous recording of glial membrane potential and the neuronal unit activity as well as extracellular DC potential and surface DC potential during SD was performed and the TTX-treated cortex was compared with the normal state. TTX did not change the DC level of the cerebral cortex. SD could be evoked by KCl when neuronal discharge was completely abolished by TTX application...


Auditory localization: role of auditory pathways in brain stem of the cat.

Cats were trained to localize sound in space. The animals' localization accuracy was determined before and after one of the following operations: 1) transection of the trapezoid body, 2) unilateral and 3) bilateral transection of the lateral lemniscus, 4) unilateral and 5) bilateral transection of the brachium of the inferior colliculus. The results after bilateral transections of the lateral lemniscus and the one deep bilateral transection of the brachium of the inferior colliculus indicate that some portion of the ascending auditory system must be intact above the medulla for an animal to be able to localize sound. A small loss in accuracy of localization was found after unilateral transection of the lateral lemniscus or brachium of the inferior colliculus. This loss, when compared with the much larger loss that monaural animals show, is an indication that binaural analysis, important for sound localization, occurs at the level of the medulla. Some transections of the trapezoid body resulted in a deficit in localization ability that appeared to be complete and permanent. The position of the lesions in the trapezoid body indicated that important encoding of the binaural cues to localization most likely occurs at the superior olivary complex, probably at the medial superior olive. But the trapezoid body or other commissures of the brain stem auditory system are probably also involved in transmission of information necessary for localization to higher centers.


Entrainment of motor-unit discharges as a neuronal mechanism of synchronization.

The neuronal mechanism which gives rise to the synchronization of motor-unit discharges has been inferred from an analysis of the interspike intervals of individual motor-unit discharges recorded from the soleus muscle. The motor units were divided into two groups on the basis of characteristic changes in their spike trains. The first group maintained a stationary discharge pattern throughout the process of synchronization with a firing rate of approximately 10 spikes/s. Small unidentified units simultaneously recorded gradually grouped around the individual spikes of the first group motor unit and with this process, high-frequency force oscillation appeared phase-locked with each of grouped discharges. The mean period of force oscillation was almost identical to the mean discharge interval. Therefore, the first group motor unit was considered as a pacemaker of this force-oscillation. The second group motor unit underwent from its initially stationary process to a transitional process characterized by spike dropouts from an otherwise regular spike train. When both groups of motor units were recorded by the same electrode, it was found that the firing rate of the second group motor unit discharges gradually approached that of the first group, and the spikes of the first and the second group motor units occurred near or at the same time. The number of double intervals decreased in a highly predictable fashion with an increase in a firing rate. It was furthermore observed that the spikes of a given motor unit whose discharges interval-to-period ratio is smaller at the beginning of transitional process was entrained to the first group motor-unit discharges with a faster time course than the unit whose discharge interval-to-period ratio is larger. The synchronizing process was described from the relations between shorter discharge interval-to-period ratios and the longer-to-shorter interval ratios obtained at several stages from the beginning of transitional process to the final synchronization. Their relations were best drawn by the second-order regression lines. The faster time course of synchronization was reflected in the larger value of coefficient a in the equation. The results of this and previous study (23) further provided evidence to justify that interaction of motor-unit discharges is responsible for the synchronization. Although the neuronal limiting device of the firing-rate control to approximately 10 spikes/s still remains unsolved, the possibility was considered that a disinhibitory neuronal network first acts to synchronize independently firing motoneurons and leads to the oscillation of the stretch reflex loop. This closed-loop system was considered as a site for the stored motor program and the use of disinhibitory neuronal network was discussed in relation to the Harmon's model of neuromimes.


Cross connections among crayfish claw efferents.

Spontaneous and reflex spike trains in the efferent neurons to the claw opener and closer muscles of the crayfish were cross correlated. The opener inhibitor and the slow closer excitor were found to be closely synchronized under all conditions. Details of the correlation suggested an electrical synapse coordinating these neurons, possibly bidirectional, but possibly from CE to OI only. The OE-OI cross correlogram showed signs of direct central inhibition of OE to OI. Polysynaptic inhibition of OI by OE may also occur. CI and OI show signs of mutual inhibition. An unidentified closer bundle efferent was strongly and positively correlated with OE. The results are consistent with the respective muscular effects of the pairs of neurons involved; they disagree, however, with some previous findings (19).


Neural repetitive firing: a comparative study of membrane properties of crustacean walking leg axons.

1. Repetitive activity and membrane conductance parameters of crab walking leg axons have been studied in the double sucrose gap. 2. The responses to constant current stimulus could be classified into three catagories; highly repetitive with wide firing frequency range, type I; highly repetitive with narrow frequency range, type II; and nonrepetitive or repetitive to only a limited degree, type III. The minimum firing frequency for type I axons was much greater than for other recording techniques. 3. Voltage-clamp currents in type III axons were qualitatively similar to those of squid or lobster axon. 4. The outward membrane currents of type I and II axons showed a transient phase in addition to the usual delayed current. The magnitude of this transient was a function of both the holding and test voltages. 5. The direction of the transient current reversed in potassium-rich saline. 6. The type I repetitive response in the walking leg axons appears to be generated by the same types of conductance changes that have been demonstrated in molluscan central neurons.


Activity of single motor units from human forearm muscles during voluntary isometric contractions.

1. Microelectrode recordings from single motor units of the first dorsal interosseus and the extensor indicis muscles of normal human subjects were studied during voluntary, isometric contractions. The conduction velocity of the nerve fiber innervating the muscle unit was used as an estimator of the size of the motoneuron. 2. During slowly increasing contractions, the units were recruited at force levels which were closely correlated to conduction velocity. The units associated with low conduction velocity were recruited first, those with high conduction velocity, last. 3. If small, stepwise force increments were used instead of slowly, continuously increasing contractions, the units were first activated during the steps and became inactive during the subsequent plateaus. If higher steady-force levels were reached, the activity was maintained also during the plateaus. This steady force, where a unit remained continuously active independent of the rate of rise of tension, represents its tonic threshold. 4. The tonic threshold is positively correlated with conduction velocity, as is the threshold force of recruitment. As a consequence, high-threshold units have a large force range below tonic threshold where they can only be transiently activated, whereas low-threshold units have a large physiological force range above tonic threshold where they operate tonically. The phasic or tonic appearance of discharge pattern reflects quantitative differences in tonic threshold between units of different size. All units examined could be activated phasically (below) and tonically (above tonic threshold). No evidence was found indicating the existence of two qualitatively different classes of units corresponding to a tonic and phasic type, although both muscles investigated consist of about equal numbers of type I and type II muscle fibers. 5. The change in firing rate per unit force was inversely related to conduction velocity: the slower conducting units showed larger changes in firing rate per unit force than faster conducting units. This corresponds to the larger excitability of the smaller units indicated by their earlier recruitment. 6. The data of this study are consistent with the hypothesis that the functional characteristics of human motoneurons are determined by the graded excitability of motoneurons according to size.


Responses of red nucleus neurons to antidromic and synaptic activation.

An account is given of the responses of 432 red nucleus (RN) neurons with axons projecting down the spinal cord. Almost half were in an initial series of 18 experiments on anesthetized cats, and the remainder were in a second series of 12 experiments on decerebrate unanesthetized cats. The differences between the two series were of little significance. All recording was from single neurons using extracellular glass microelectrodes that were inserted throught the right superior colliculus and directed to the right red nucleus at a standard orientation. Identification of RN neurons was both by location, checked by subsequent histology, and by antidromic invasion from the spinal cord. The spinal stimulating electrodes were placed in proximity to the left rubrospinal tract at C2 and L2 segmental levels. Axonal conduction velocities were calculated from the latency differential between the L2 and C2 antidromic responses and were usually in the range 60-130 m/s, 97% of all neurons located in the red nucleus had axons projecting to the C2 level, and 37% projected to the L2 level. The responses of 229 RN neurons were observed with stimulation applied to the contralateral (left) interpositus nucleus. In 10 (5%) there were antidromic responses to both interpositus and C2 stimulation, a finding in good agreement with the anatomical description of rare axon collaterals from rubrospinal fibers to the interpositus nucleus. In 209 (91%), there was a clear monosynaptic excitation. The impulse generation was at a latency usually of 1.0-1.8 ms, which a modal value of 1.4 ms. The afferent inputs to RN neurons were provided by stimulation either of predominantly cutaneous nerves in all four limbs or of cutaneous mechanoreceptors of the contralateral forelimb and hindlimb...


Somatotopic studies on red nucleus: spinal projection level and respective receptive fields.

The somatotopic inputs into red nucleus (RN) neurons have been studied with special reference to their level of projection in the spinal cord. As inputs we employed either volleys in predominantly cutaneous nerves of forelimb and hindlimb or cutaneous mechanoreceptor discharges evoked by taps to footpads of forelimb and hindlimb. There has been physiological confirmation of the anatomical findings that RD neurons projecting to the lumbar cord are located in the ventrolateral zone of the pars magnocellularis, whereas in the dorsomedial zone are RN neurons with cervical but not lumbar projection. Somatotopically there was found to be a differentiation of input to RN neurons according as they projected to the lumbar or only to the cervical cord. This finding was presented in the form both of tables and of somatotopic maps. As expected, this discrimination was more restrictive for the more selective inputs from pad taps than for nerve inputs. Nevertheless, forelimb inputs often had a considerable excitatory and inhibitory action on lumbar-projecting RN neurons, and vice versa for cervical-projecting neurons. There were two notable somatotopic findings that suggest specificities of connectivities. First, despite the large convergence of IP neurons onto RN neurons (about 50-fold), the degree of somatotopic discrimination was about the same for interpositus and RN neurons with two testing procedures: between inputs from forelimb and hindlimb; and between inputs from pads on one foot. Second, although there was in the interpositus nucleus a considerable topographical admixture of neurons with dominant forelimb or hindlimb inputs, the axonal projections of these neurons were apparently unscrambled on the way to the target RN neurons, so as to deliver the somatotopic specificities observed for two classes of RN neurons; those projecting down the spinal cord beyond L2 level, and those projecting to C2 but not L2. Finally, there is a general discussion of motor control with reference to the pathway; pars intermedia of anterior lobe of cerebellum leads to interpositus nucleus leads to red nucleus leads to rubrospinal tract leads to spinal motoneurons.


Increases in reflex excitability of monkey masseter motoneurons before a jaw-bite reaction-time response.

Reflex excitability of the motoneurons innervating the masseter muscle of monkeys was tested before a phasic voluntary activation of the jaw-closing muscles (a RT bite response). Single test shocks were delivered to the Mes V which supplies a monosynaptic excitatory input to the jaw-muscle motoneurons. Changes in reflex excitability were assessed by measuring the amplitude of the synchronous muscle potential evoked by the test shock. Amplitudes of the muscle potentials evoked by shocks which occurred just before the beginning of the voluntary EMG response, as judged by the onset of EMG activity of the masseter muscle contralateral to the test shock were many times larger than potentials evoked immediately following the visual RT stimulus. Curves relating the average amplitude of the evoked response to its time before the beginning of the voluntary response suggest that the reflex excitability of the motoneuron pool begins to increase 25-45 ms before the first detectable EMG activity occurs. These results suggest that inputs arrive at the motoneurons of agonist muscles used in rapid RT tasks substantially before changes in the EMG of the muscle are noted. These results, in part, would account for the time interval noted between the beginning of neural activity in suprasegmental structures which presumably excites spinal motoneurons, and the first EMG activity of muscles which are innervated by these motoneurons.


Intracranial pressure, blood pressure, and pulse rate after occlusion of a middle cerebral artery in cats.

The left middle cerebral artery was occluded in 12 tranquilized but unanesthetized cats with use of a device implanted transorbitally 5 to 7 days earlier. Bilateral epidural pressures, mean aortic blood pressure, and pulse rate were measured at intervals for up to 48 hours after occlusion. The relationships of these measurements to each other and to the extent and severity of cerebral infarcts is described.


Chronic cerebral arterial spasm. The role of intracranial pressure.

The author used isolated rabbit common carotid and femoral arteries perfused at a constant pressure of 90 mm Hg to examine the variation of flow (F) with transmural pressure (TMP). When the TMP was reduced below 50 to 60 mm Hg in arteries with normal smooth muscle tone, arterial resistance increased significantly causing a reduction in flow. It is suggested that the diffuse arterial narrowing that occurs in patients with severe intracranial hypertension may be the result of a similar reduction in TMP. In the presence of active vasoconstriction, any increase in extraluminal (intracranial) pressure (ICP) resulted in a substantial increase in arterial resistance and subsequent reduction of flow. This F-TMP relationship depended only on the initial degree of constriction and was independent of the vasoconstrictor used to achieve this constriction and of the artery in which this constriction was produced. A review of the literature suggests that human cerebral arteries normally exhibit only mild constrictions in response to subarachnoid blood during the chronic phase of spasm. In the present study, a mild constriction in the absence of increased ICP or a moderate increase in ICP (45 mm Hg) in the absence of constriction produced minor reductions in arterial diameter and an average flow reduction of only 5% to 10%. However, when ICP was increased to 45 mm Hg in the presence of a mild constriction, severe arterial narrowing resulted and flow was reduced by 50%. Therefore, it is suggested that chronic arterial spasm is the result of a mild constriction which is amplified by the simultaneous occurrence of increased ICP. Phenoxybenzamine was found to be effective in reversing and preventing these contractions. The improvement in flow produced by phenoxybenzamine decreased as the TMP was reduced below 60 mm Hg. The effects of both diffuse and local spasm on cerebral blood flow are discussed.


Management of ischemic complications after subarachnoid hemorrhage.

The author reviews a form of management for patients deteriorating preoperatively or postoperatively from apparent ischemia attributed to progressive vasospasm after a subarachnoid hemorrhage. The clinical picture and relative frequency of this complication are considered in relationship to the status (grade) of the patient, location of the aneurysm, and ultimate neurological recovery. Experience suggests that the drug regimen reported is useful when instituted early after the onset of symptoms and is safe with proper monitoring techniques. The data do not justify early operative intervention after a subarachnoid hemorrhage, operation when there is angiographic evidence of severe spasm, or expectation of a dramatic effect in patients with a profound deficit or a fixed deficit several hours old.


Proximal occlusion of the anterior cerebral artery for anterior communicating aneurysm.

Results of proximal anterior cerebral artery occlusion are described in 68 patients with anterior communicating artery aneurysms. The procedure is found useful in the treatment of these aneurysms because of its technical simplicity and the low rates of mortality and morbidity achieved.


Pituitary adenomas of adolescents.

A review of four cases of chromophobe adenomas in adolescents suggests that extracapsular extension with invasion of parasellar structures is more common in this age group than in adults. A syndrome of adolescent obesity, oculomotor palsies, and plain x-ray changes of the sella characterizes this group.


Use of the operating microscope in anterior cervical discectomy without fusion.

The authors report their experience using the operating microscope in 52 anterior cervical discectomies without fusion. They found long-term results highly satisfactory, even in difficult cases with multiple-level disease, and complications from bone grafting were obviated. They highly recommend this approach for radicular, nonradicular, or myelopathic symptoms.


Experimental hydrosyringomyelia, ischemic myelopathy, and syringomyelia.

The authors found that cavities in the spinal cord of dogs appearing after the intracisternal administration of kaolin are not due to ischemic softening, but rather to distention and subsequent rupture of the central canal. Ischemic lesions could be produced and were found to have a quite different histopathology; this supports the hydrodynamic hypothesis of cavitary myelopathy following adhesive arachnoiditis, probably as a compensatory mechanism to the associated hydrocephalus. The similarities to human syringomyelia are discussed.


Evaluation of postcraniotomy patients by radionuclide scan.

Twenty-eight patients with cerebral tumors were evaluated after craniotomy with combined radionuclide techniques in order to assess presence or absence of tumor recurrence. The combination of a positive pertechnetate or Tc-phosphate scan with a positive gallium scan strongly indicates the presence of recurrent or residual tumor. Infection may also cause uptake but was easily distinguished by the distribution. Negative gallium scans with positive technetium scans  were indicative of non-recurrence in this series.


Abdominal pseudocysts and ascites formation after ventriculoperitoneal shunt procedures. Report of four cases.

The authors report three patients with abdominal pseudocysts and one with cerebrospinal fluid ascites as late complications of ventriculoperitoneal shunts. The presenting signs and symptoms were those of intraabdominal abnormality, with no neurological symptoms suggestive of shunt malfunction.


Spontaneous umbilical fistula from ventriculoperitoneal shunt drainage. Report of two cases.

Two cases of spontaneous fluid fistula through the umbilicus connected with the drainage from a ventriculoperitoneal shunt are described. In neither case was it necessary to remove the shunt.


Spinal cord compression by extramedullary hemopoietic tissue in sickle cell anemia. Case report.

The authors report a patient with sickle cell anemia who suffered from paraplegia of 18 months duration due to spinal cord compression by a hemopoietic mass. Recovery following removal of the mass was complete.


Complete embolization of artery of Adamkiewicz to obliterate an intramedullary arteriovenous aneurysm. Case report.

A case history of an intramedullary arteriovenous aneurysm of the thoracolumbar junction is presented, and an unusual 14-year follow-up after the original sub-arachnoid bleeding episode is detailed. Embolization of anterior and mixed angiomas involving the artery of Adamkiewicz may be feasible when the artery is large and shunting is present.


Tuberculous brain abscess. Case report.

The authors describe a case of tuberculous cerebral abscess of the frontal lobe that developed 1 year after an episode of acute miliary tuberculosis. The development of such a lesion indicates a persistence of infection and an immunological breakdown which may partly have been due to protein malnutrition.


Giant suprasellar aneurysm associated with optic stalk agenesis and unilateral anophthalmos. Case report.

The authors report a patient with unilateral anophthalmos who had a large suprasellar aneurysm associated with aplasia of an optic nerve and the chiasmal commissure. The anatomical findings at craniotomy are described.


Persistent proatlantal artery with carotid-vertebral anastomosis. Case report.

The authors describe the occurrence of proatlantal artery as an incidental angiographic observation in a young Indian soldier. This primitive anastomotic channel is seen extending from near the origin of the external carotid artery to the suboccipital region, traversing the foramen magnum and coursing beyond like a vertebral artery. The developmental and roentgenological aspects of carotid-basilar and carotid-vertebral anastomosis are discussed, along with a review of four similar cases reported previously.


Significance of absent or faint kidney sign on bone scan.

Seven men, six suffering from widespread bone metastases of prostatic origin and one with urinary bladder carcinoma, demonstrated minimal or no discernible radioactivity in the kidneys and urinary bladder at the time of bone scanning using 99mTc-stannous polyphosphate. The mechanism behind this scan finding is thought to be rapid and enhanced uptake of the radiopharmaceutical by pathologic bone. The significance of the faint or absent kidney sign in bone scanning, particularly in cases where abnormally homogeneous and symmetric radioactivity exists, is discussed.


Abnormal spleen scan following MOPP therapy in a patient with Hodgkin's disease: case report.

A patient with Stage IV-A nodular sclerosing Hodgkin's disease is described who, at initial presentation, demonstrated an apparent large filling defect in the spleen by 99mTc-sulfur colloid scan. Following a 6-month course of MOPP therapy, the patient was clinically free of disease although the spleen scan remained unchanged. After laparotomy, the spleen was found to be entirely normal histologically.


Intracerebral hemorrhage demonstrated by nuclear cerebral angiogram: case report.

Two intracerebral hemorrhages were detected because of vascular displacement on the radionuclide cerebral angiogram. The static brain images in both patients were normal.


Visualization of nonvascular cranial tumor in cerebral flow study: case report.

Unusual results were obtained from a cerebral blood flow study and a brain scan performed on a patient with an uncommon, nonvascular scalp tumor eventually identified as a proliferating trichilemmal cyst with acanthosis. The tumor accumulated the radionuclide during the early phase of the cerebral flow study, and the increased radioactivity was persistent, being prominently observable in a scan made 3 min and 2 hr after the radionuclide injection. This unusual, positive finding in a cerebral blood flow study of a nonvascular tumor was thought to be a consequence of the higher counting efficiency resulting from the lack of shielding by the skull and from the larger volume of the tumor tissue.


Persistent left superior vena cava demonstrated by radionuclide angiocardiography: case report.

This report presents a patient with a persistent left superior vena cava demonstrated by radionuclide angiocardiography. The appearance is characteristic.


Labeling and testing of 99mTc-streptokinase for the diagnosis of deep vein thrombosis.

A detailed study has been made of the method for labeling streptokinase with 99mTc in order to get a radioactive indicator for rapid scintigraphic visualization of thrombi and emboli. The best method found for preparing 99mTc-streptokinase was by reducing 99mTc-pertechnetate with  2 mumole SnCl2 at pH 0.7 and then adding 50,000-75,000 IU of streptokinase at a final pH of about 2. After 1 hr of equilibration the labeling efficiency was 75-80% as determined by the method of gel chromatography column scanning. The dynamic behavior and distribution of 99mTc-streptokinase in different organs was studied in rabbits where a high uptake was found in liver. In a clinical investigation using 99mTc-streptokinase prepared according to this work, however, the liver uptake in man was only 10-20%.


Vesicle interactions with polyamino acids and antibody: in vitro and in vivo studies.

Artificial spherules or vesicles of 900 A in diameter formed from phosphatidylcholine and gangliosides and enclosing 99mTcO4 - (standard preparation) survive intact in the circulation of the mouse. Polyamino acids and protein have been incorporated into and onto the vesicles; such vesicles remain intact as determined by diffusion dialysis studies and by electron paramagnetic resonance studies of vesicles enclosing spin label. In studying the distribution of polyamino acid-vesicles and protein vesicles in vivo, it was found that the latter distribute differently from standard vesicles or free protein alone whereas aromatic polyamino acid-vesicles concentrate in the liver and spleen to a greater extent than standard vesicles. We conclude that the permeability and stability characteristics of vesicles may be preserved when they are modified by the addition of protein or polyamino acids and that such modification of vesicles may be associated with an alteration of their fate in vivo. The potential exists to use vesicles as carriers of radiopharmaceuticals and other drugs and to direct the vesicles preferentially to tissue targets in vivo.


In vivo distribution of vesicles loaded with radiopharmaceuticals: a study of different routes of administration.

The in vivo distribution of vesicles containing radiopharmaceuticals in their cavities has been studied using three routes of administration: intravenous, subcutaneous, and intraperitoneal. The in vivo distribution in mice was determined by dissection of the animals and calculation of radioactivity in the organs. In rats the in vivo distribution was assessed by scintigraphy using a scintillation camera-digital computer unit. After intravenous injection of vesicles, radioactivity is concentrated to some extent in the liver and spleen but the pattern of distribution is different from that of the corresponding free radiopharmaceutical or radiocolloid made of the corresponding radionuclide. The permeability of the vesicular membrane to contained radiopharmaceutical has been shown to vary according to the chemical composition of the vesicles. Vesicles can be used to introduce materials in vivo and the potential exists for their specific targeting by coupling other molecules to their surfaces.


Use of tissue-to-air ratio in computation of specific absorbed fraction.

This paper describes a new approach for computing specific absorbed fractions that can be used for estimating doses that result from the internal administration of radiopharmaceuticals. This approach uses the concept of the tissue-to-air ratio (TAR) which can either be calculated or experimentally determined for the radionuclides of interest. Good agreement exists between the specific absorbed fraction values obtained using measured and computed values of TAR. This implies that the measured values of TAR can be used to obtain specific absorbed fractions for all radionuclides.


Determination of the bromide space in man by fluorescent excitation analysis of oral bromine.

The bromide dilutional volume determined by intravenous administration of 82Br has been compared with the corresponding volume determined by oral administration of stable bromide in 11 patients with various medical disorders. Stable bromide was assayed by fluorescent excitation analysis using a 109Cd source and a lithium-drifted silicon detector. The average deviation between the fluorescent and the radiobromide dilutional volumes was 4.2% with a standard deviation of +/- 8.5%. This substantiates both the accuracy of the fluorescent excitation method as applied to this tracer and the validity of utilizing oral tracer administration in comparison with intravenous administration. The derived estimates of extracellular fluid volume averaged 28.7% of body weight in the entire group of 11 patients and 25.8% in the 4 normal subjects included in the group. Evaluation of the extracellular fluid space utilizing fluorescent excitation of stable bromide permits high statistical accuracy of sample measurement with great simplicity compared with current chemical methods and with avoidance of the patient radiation exposure associated with 82Br.


Glycopyrrolate in 99mTc-pertechnetate brain imaging.

Glycopyrrolate, a synthetic anticholinergic agent, was administered parenterally to two groups of patients referred for 99mTc-pertechnetate brain imaging to assess its ability to suppress pertechnetate uptake by the choroid plexus, oral mucosa, and salivary (parotid) glands. Pertechnetate activity was almost completely eliminated from the choroid plexus and mouth and appeared to be moderately reduced in the parotid gland. The drug can be given orally and may prove valuable in pertechnetate brain imaging.


The spleen-lung interface as diagnostic information.

Left anterior, lateral, and posterior views on 50 consecutive RES-lung scams were examined. Normal patients had continuity of activity between the left lung and the spleen on all three views. Patients with subphrenic abscess or large left pleural effusions showed no continuity between lung and spleen activity on any view, while other abnormalities, most commonly cardiomegaly, accounted for lack of lung-spleen continuity on the anterior view only. It is suggested that in all combined RES-lung studies, the left side be examined as well as the right for abnormalities adjacent to the left diaphragm.


Scintigraphy in a case of pseudocyst of liver: case report.

Pseudocyst of the liver resulting from bile leakage into subcapsular region from undetermined cause is described. Liver scintigraphy was correlated with the operative findings.


Posterior fossa scintiangiography: documentation of genetic penetrance of von Hippel-Lindau syndrome in a clinically unaffected girl and her father.

The 16-year-old clinically normal daughter of a patient with the von Hippel-Lindau syndrome demonstrated a vascular posterior fossa lesion on scintiangiography that failed detection in delayed images. Contrast arteriography corroborated the presence of a hemangioblastoma. Noninvasive demonstration of the genetic penetrance of this disorder offers its victims an opportunity for low morbidity early surgical cure of the associated brain lesions.


Radionuclide cerebral angiographic evaluation of a diploic extracranial meningioma: case report.

A case of a diploic extracranial meningioma whose true vascularity was more significantly defined by radionuclide angiography than by selective contrast angiography is presented. The radionuclide angiogram clearly demonstrated large venous channels draining the tumor.


Myocardial uptake of labeled oleic and linoleic acids.

Oleic acid labeled with 14C, (14C-OA) or 131I (131I-OA) and 131I-labeled linoleic acid (131I-LOA) were administered intravenously to rats and tissue distribution studies completed at various time intervals from 5 to 60 min. Tissue distribution of 131-I-labeled oleic acid or linoleic acid was also studied in dogs at 5- and 30-min time intervals after intravenous administration of the tracer dose. There were distinct differences in the patterns of tissue distribution between 14C-OA, 131I-OA, and 131I-LOA. Radioactivity concentration in the myocardium was the highest at all time intervals in the rats given 131I-OA only. In dogs, the myocardial uptake of 131I-OA was significantly higher than the radioactivity in the blood or other tissues at 30 min after injection. The disappearance rates of 131I-OA and 131I-LOA were almost identical but myocardial concentration of 131I-LOA at 30 min after the dose in the dog was half that of 131I-OA whereas 131I-LOA liver concentration was higher than that of 131I-OA. Since the concentrations of our formulated 131I-OA in the blood and in the myocardium are both highest at the earlier intervals, it should be difficult to detect myocardial ischemia or infarction with 131I-OA scanning.


Radiation dose to the human body from intravenously administered 75Se-sodium selenite.

The dose of radiation to the human body and some of its organs after intravenous administration of 75Se-sodium selenite for diagnostic purposes has been calculated on the basis of followup of 26 patients for as long as 517 days with measurements of: 1. The retention of 75Se in the whole body. 2. The retention of 75Se in the blood, liver, kidneys, ovaries, testicles, and hair. 3. The excretion of 75Se in urine and feces. Whole-body counting and profile scanning were done on the patients and samples of blood from different organs, urine, and feces were measured for radioactivity. The dose of radiation received was calculated for an average patient of 70 kg. These doses were found to be slightly higher than previously reported on a smaller number of patients and with a shorter follow-up. They were slightly lower than those from 75Se-methionine to the whole body but higher to the liver and kidneys. The margin of error in this investigation was estimated to be about 20% for the whole-body dose and probably higher for different organs, mostly due to the poorly known rate of retention of selenite in different organs.


Lack of effect of cecectomy on oxygen consumption and colonic temperature of germfree rats.

Oxygen consumption and colonic temperature of germfree rats are lower than those of conventional and conventionalized rats. Cecectomy of weanling germfree rats prevents the development of the very large ceca characteristic of ordinary germfree rats but did not increase oxygen consumption or change colonic temperature.


Induction of fatty liver by ethanol drinking in KK and KK-Ay mice.

Marked fatty liver was found to develop in both KK and KK-Ay (yellow KK) mice when they were allowed free access to a 15% ethanol solution as drinking fluid. The present studies were undertaken to elucidate the characterization of the fatty liver and associated changes. Chemical analysis showed that accumulated lipids were mainly triglycerides, whose fatty acid composition was changed with increases in palmitoleic and oleic acids, indicating augmentation in endogenous lipogenesis. An accumulation of small fat droplets was histologically observed in centrolobular hepatocytes extending to perilobular zones. Among the tested mice of seven strains, only KK and KK-Ay mice developed the ethanol-induced fatty liver, and the latter mice were more susceptible. Growth, food and alcohol intakes, plasma levels of glucose, triglycerides, and immunoreactive insulin were also surveyed during the development of the alcoholic fatty liver. In contrast to high energy diet, ethanol induced neither development of obesity nor exaggeration of diabetic states. A possible correlation between the pathogenesis of the fatty liver and the genetic factor inherited in KK mice is discussed.


Influence of dietary lipids on iron and copper levels of rats administered oral contraceptives.

Interrelationships between oral contraceptives and dietary lipids on iron and copper levels in plasma and tissues were investigated in rats. Diets containing either 20% (by weight) safflower oil or hydrogenated coconut oil with and without cholesterol (0.5%) were fed to weanling, female, Wistar-strain rats for a period of 19 weeks. Three types of oral contraceptive agents differing in estrogen/progesterone ratios were administered during weeks 16 through 19 of the experiment. Control rats received the dietary treatment without oral contraceptives. Hemoglobin concentration, hematocrit, red blood cell counts, mean cell hemoglobin and hemoglobin concentration, and mean cell volume values were similar among the various dietary and drug-treatment groups. Elevated levels of copper were found in livers of drug-treated animals fed diets containing cholesterol and safflower oil, whereas levels of copper or iron in spleen and kidney were not influenced by oral contraceptives. Dietary safflower or coconut oil had no influence on levels of iron or copper in plasma. However, iron levels were higher in liver, spleen, and kidneys of rats fed coconut oil compared with those fed safflower oil. Cholesterol-fed rats had reduced levels of iron in plasma and tissues and increased levels of copper in plasma and liver. Iron deficiency in cholesterol-fed rats was indicated by low levels of iron in plasma, liver, spleen, and kidney. In experiment 2, animals were fed the 20% safflower oil diet, with and without sodium glycocholate or cholesterol, to determine whether the apparent malabsorption of iron resulted from sodium glycocholate or cholesterol. Sodium glycocholate resulted in a marked increase in the absorption of iron, whereas cholesterol depressed absorption.


Beneficial effect of increased dietary linoleate upon in vivo platelet function in man.

The effect of increasing dietary linoleate upon in vivo platelet aggregation and disaggregation in 20 males and 46 female adult humans was studied. In creasing exogenous linoleate for 2 weeks from 2.89 +/- 0.11 to 5.00 +/- 0.26% of energy was associated with the doubling of the aggregation time and halving of the disaggregation time. Decreasing dietary linoleate in the following 2-week feeding period was associated with a reversal of the effect.


Vitam A deficiency and fetal growth and development in the rat.

Studies were conducted to examine in detail the effects of vitamin A deficiency on fetal growth and development in the rat. The gradations of deficiency were examined in two studies. The first included total vitamin A depletion followed by retinoic acid supplements, and the second included three different levels of restricted intake of retinyl acetate (42, 16, or 8 mug of retinol equivalents/day/kg of body weight) in vitamin A-depleted rats. In the first study, extensive fetal resorption and death were observed in retinoic acid-fed females after day 14 of gestation. These findings confirmed the morphological studies of Thompson and associates (Proc. Roy. Soc. London, Ser. B 159, 510-535, 1964) who found the earliest Detectable histological lesions to be in the placentas at days 15-16 of pregnancy. Analyses were carried out of the total weight, the DNA, RNA, and protein contents of fetuses and placentas of different gestational ages in retinyl ester-fed and retinoic acid-fed females. Biochemical changes indicative of a reduced rate of cell division were observed in both fetus and placenta by day 14 in the retinoic acid-fed rats. The few live fetuses in this group maintained a growth rate of only 60-70% of that of the fetuses of retinyl ester-fed dams after day 14. By contrast, the growth rate of the placentas (of live fetuses) after day 14 of gestation was not as consistently affected by retinol deficiency. Restriction of retinyl acetate intake (in the second study) significantly reduced both the total litter size and the number of live pups per litter. Most of the females in the retinyl acetate-restricted groups delivered pups that had normal body weight and appeared normal on visual inspection. Significant differences from normal controls were seen only in the neonates from dams given 8 mug of retinol equivalents (per kg of body weight per day), which had smaller livers and kidneys than the control neonates. In contrast, the weights of the brains of the neonates in all three retinyl acetate-restricted groups showed no differences from control values. Vitamin A assays on maternal and neonatal sera and livers indicated that the transport of vitamin A across the placenta was well regulated, and suggested that this transport is maintained with high priority in the presence of maternal deficiency. The effects of vitamin A deficiency on fetal growth and development might reflect primary effects on the placenta, with secondary effects on the fetus, or primary direct effects on the fetus itself. The mechanisms of the observed effects remain to be explained.


Influence of genetic differences in feed efficiency on carcass composition of young chickens.

The carcass composition of young chickens differing in efficiency of feed utilization was obtained to study changes in the carcass composition associated with differences in efficiency of feed utilization. As the efficiency of conversion of food to tissue was changed, there were associated changes in carcass moisture and lipid, regardless of differences between different populations in variability for growth rate. Carcass moisture was increased and carcass lipid was decreased in chickens with relatively better conversion of food into carcass. Carcass protein was significantly increased in chickens with better efficiency of feed utilization in one population, but not in another. Changes in carcass composition associated with efficiency of feed utilization were similar regardless of whether differences in efficiency were due to gain or to a combination of gain and consumption. Significant sex differences in carcass moisture, lipid, and protein were observed in the faster-growing broiler population but not in the lines selected from a slower-growing randombred population. There was a significant decrease in 16:1 and an increase in 18:0 fatty acids of chickens with a lower feed conversion ratio.


Effect of starvation on protein synthesis in neonatal rat liver.

Hepatic protein synthesis was measured in vivo and in vitro (liver slice) in 6- and 19-day-old rats. Fed and 15-hour starved rats were compared in each individual experiment. The study demonstrated that in the 6-day-old rat, hepatic protein synthesis is very sensitive to restrictions in dietary influx. In contrast, no significant differences in protein synthesis were detected when 19-day-old rats were fasted for 15 hours. In the fed state, the protein synthetic activity of the tissue unit was the same irrespective of age. Thus, it appears that it is not the maximal capacity for protein synthesis that changes with age, but rather the extent to which the system can adapt to the changing nutritional environment.


Cystathionine excretion in relation to vitamin B-6 nutriture of rats: strain differences and effects of DL- or L-methionine supplementation.

Wistar and Long-Evans rats excreted significantly more cystathionine during days 27 to 31 of a vitamin B-6 deficiency than did Spague-Dawley rats. Wistar rats were therefore chosen for experiments designed to test the effects of dietary DL- and L-methionine supplementation upon cystathionine excretion of vitamin B-6-deficient and control rats. Methionine supplementation did not significantly affect mean daily food consumption or weight gain of the control animals. L-Methionine-supplemented, deficient rats gained significantly more during the first 15 days of the experiment and less during the last 11 days than did the other deficient groups. No cystathionine was detected in the urine of methionine-supplemented or unsupplemented control rats between days 8 and 26 of the experiment; but measurable quantities of cystathionine were present in the urine of all deficient groups by days 8 to 12. Deficient animals fed DL-methionine excreted up to 2.33 mg more cystahionine per 4-day period than did the unsupplemented deficient rats, whereas rats fed L-methionine excreted up to 7.44 mg more per 4-day period than did the unsupplemented ones. This difference in cystathionine response was highly significant and indicates that the L supplement stressed the vitamin B-6-deficient rats more than did the DL supplement. An explanation for this may be that the D isomer in the DL supplement was not as efficiently absorbed and/or metabolized as the L form.


Effects of skim milk, whole milk and light cream on serum tryptophan binding and brain tryptophan concentrations in rats.

One hour after rats fasted for 13 hours consume a single meal of skim milk, whole milk, or light cream, serum nonesterified fatty acid (NEFA) concentrations changed in direct proportion to the fat content of the diet: serum NEFA levels decreased in rats ingesting skim milk (0.09% fat) to 34% of fasting control values; in animals consuming whole milk (3.59% fat), levels dropped to 50% of fasting levels; these levels did not change significantly, however, in rats consuming light cream (18.26% fat). The percentages of total serum tryptophan not associated with albumin in rats ingesting skim milk, whole milk, or light cream were 22.2, 26.0, and 42.5%, respectively. These variations in serum free tryptophan were not accompanied by significant differences in brain tryptophan among the three treatment groups. These results thus confirm that, with a natural food source, (a) postprandial serum NEFA levels reflect the total fat content of the diet; (b) serum free tryptophan concentration shift proportionately with serum NEFA; and (c) serum free tryptophan concentrations do not reliably predict brain tryptophan levels.


Involvement of food intake in the lysine-arginine antagonism in chicks.

Studies were conducted to evaluate the involvement of food intake in the lysine-arginine antagonism. Diets were formulated to compensate for the metabolic consequences of excess dietary lysine; induction of renal arginase activity, depression of heptic glycine transamidinase, and urinary losses of arginine. This was accomplished by inclusion of creatine in the basal diet, use of a moderate excess of lysine that did not increase urinary arginine excretion, and addition of the arginase depressors, alpha-aminoisobutyric acid (AIB) and L-threonine, to diets containing excess lysine. When chicks were fed diets containing excess lysine ad libitum, growth and efficiency of arginine retention were reduced. Supplementation of the diets with AIB and threonine markedly reduced the growth depression and restored efficiency of arginine utilization. When chicks were force-fed the diet containing excess lysine, growth was depressed, and body composition was altered. Inclusion of AIB and threonine in the diet containing excess lysine resulted in growth and body composition equivalent to levels of force-fed controls. In a second experiment the basal diet and basal supplemented with AIB and threonine were pair-fed to lysine-supplemented diets containing AIB and threonine. Body weight gains and body composition of all groups were similar. In other experiments, food intake increased within 24 hours (P less than 0.05) and probably within 12 hours (P less than 0.10) after removal of excess lysine from the diet. It is concluded that a portion of the lysine-arginine antagonism is due to a primary effect of lysine on regulation of food intake.


Effect of meal-feeding on the daily variations of insulin, glucose, and NADP-linked dehydrogenases in rats.

Normal and adrenalectomized rats were either ad libitum fed or meal-fed a 66.5% glucose diet for 1 to 3 weeks. Ad libitum-fed rats exhibited synchronized daily rhythms in the levels of immunoreactive insulin, glucose, hepatic glucose-6-phosphate dehydrogenase, and malic enzyme activities. These rhythms were shifted late-morning 2-hour feeding period. The rhythms of adrenalectomized ad libitum-fed rats were different from those for nonadrenalectomized rats. These results indicate that differences between ad libitum- and meal-fed animals may be attributable to the timing of food intake with respect to the timing of observation rather than to meal-feeding alone. It is further concluded that the adrenals play a role in the maintenance of these rhythms.


Effects of carbohydrate-free diets on the insulin-carbohydrate relationships in rats.

Insulin-carbohydrate relationships were investigated in four groups of young rats fed low protein diets differing in carbohydrate and fat contents: (1) a diet in which the nonprotein energy was provided by fatty acids (FA); (2) a similar diet in which the fatty acids were substituted by neutral fat (NF); (3) FA diet supplemented with glycerol (FA-Glyc); and (4) a carbohydrate-rich diet (HC). Control rats were fed a stock diet. Rats fed the FA diet lost weight, were hypoglycemic and hypoinsulinemic in the fed state and normoglycemic and normoinsulinemic in the fasted state, and had an impaired glucose tolerance and hyperinsulinemia after a glucose load. Liver and muscle glycogen were low in fed rats. Fasting increased glycogen in liver and decreased glycogen in muscle. NF animals gained weight, were hypoglycemic in both fed and fasted states, and their plasma glucose level after an oral glucose load was almost normal. Plasma insulin/glucose ratio, both in fed and fasted states and after a glucose load indicated hyperinsulinism, which was accompanied by obesity. Muscle and liver glycogen were low in fed animals and did not change after a fast. Supplementation of the FA diet with glycerol (FA-Glyc) abolished weight loss and fasting hyperglycemia and normalized plasma glucose and insulin response to a glucose load. Rats fed the HC diet had an improved glucose tolerance and an increased sensitivity to insulin. Liver glycogen was high in the fed state and normal in the fasted state, whereas muscle glycogen was normal in both nutritional states.


Effects of riboflavin repletion during different developmental phases on behavioral patterns, brain nucleic acid and protein contents, and erythrocyte glutathione reductase activity of male rats.

Effects of riboflavin repletion of rats at various stages of development were evaluated by biochemical and behavioral parameters. One group of dams received diets containing a suboptimal level of riboflavin, approximately 15 mug, and another group, control, received approximately 40 mug of the vitamin daily 2 weeks before mating. Rats fed the control diet received approximately 120 mug riboflavin daily during pregnancy and lactation; suboptimals received approximately 15 mug daily. Some rats fed the control diet were pair-fed to rats fed the suboptimal ration. A group of dams fed the suboptimal diet was switched to control after parturition. At weaning, male offspring were fed the same riboflavin levels their respective dams received before mating except one group, whose dams were fed the suboptimal diet, received the control diet. Male progeny of dams pair-fed the control diet to suboptimal rats were either pair-fed to offspring of suboptimal dams or to offspring riboflavin-repleted at weaning. Rats that always received the suboptimal diet had significantly higher general activity scores at 60 days of age than the scores of other animals. Brains from rats always fed the suboptimal diet and those receiving riboflavin repletion at weaning had lower, sometimes significantly, DNA, RNA, and protein contents than those from other animals. Riboflavin restriction during gestation and lactation, but not gestation alone, appeared to produce permanent alterations in general activity scores and brain nucleic acid and protein contents of male rat progeny.


Failure of balance measurements to predict actual retention of magnesium and calcium by rats as determined by direct carcass analysis.

Magnesium (Mg) and calcium (Ca) balances as well as determinations of atomic absorption analysis of atomic absorption analysis of total absolute contents of Mg and Ca fat-free dry carcasses were done on gnotobiotic male Sprague-Dawley rats, kept at 28 degrees or 6 degrees, for 69, 240, or 517 days, and fed either a commercial stock diet or a semipurified diet containing a normal or a subnormal amount of Mg. The often-reported observation of negative balances when Mg intake is subnormal has been confirmed. Total Mg and Ca accumulation in the carcass estimated from balance values was totally inconsistent with the actual content of the carcass as determined by direct analysis. The large discrepancy between the actual analysis of the carcass and the estimated content of Mg and Ca in the carcass derived from balance data demonstrates clearly that balance of trace minerals cannot reflect chronic retentions or losses of these minerals. Possible explanation of this discrepancy are dissussed.


Methionine toxicity in the chick: nutritional and metabolic implications.

Several assays with young chicks fed crystalline amino acid diets were conducted to investigate the effects of supplemental glycine, serine, threonine, arginine, or adenine on the growth depression resulting from consumption of excess methionine. Glycine was partially effective in alleviating the growth depression caused by excess methionine. The addition of threonine together with glycine improved performance still further. Efficiency of food utilization for weight gain was greater in birds fed the methionine-imbalanced diet supplemented with glycine and threonine than in those fed the control diet. Supplemental glycine, threonine, or adenine, but not arginine, was effective in ameliorating the hypoglycemia resulting from consumption of excess methionine. The rate of oxidation of a tracer dose of threonine was increased markedly by feeding 1.25% excess methionine. This was reflected in a 20% depression in threonine utilization for weight gain as measured by slope ratio. The data suggest that both threonine and glycine are antagonized by consumption of excess methionine.


Effect of pancreatectomy or adrenalectomy on the responses of rats to meal-feeding.

The effects of partial pancreatectomy or adrenalectomy and insulin or corticosterone replacement on the responses of rats to meal-feeding were studied. Partial pancreatectomy lowered glucose-6-phosphate dehydrogenase (G6PD) and malic enzyme (ME) activities and resulted in higher blood glucose levels. Partial pancreatectomy did not affect the ability of the animals to adapt to meal-feeding. Insulin supplementation of the pancreatectomized rats restored G6PD and ME activities to those observed in the intact animals and normalized the blood glucose levels in the ad libitum-fed rats. Adrenalectomy decresed the survival of rats subjected to meal-feeding. Eighty percent of the rats died when meal-fed a high glucose diet. Survival was improved when either a 66.5% starch diet or a 40.5% fat diet was substituted for the 66.5% glucose diet. Adrenalectomized meal-fed animals fed 66.5% glucose had higher G6PD and ME activities and higher liver lipid levels than both the adrenalectomized ad libitum-fed and the sham-operated meal-fed rats. Glucocorticoid supplementation lowered G6PD activity in the adrenalectomized meal-fed rats but had no effect on ME activity or liver lipid. Meal-fed adrenalectomized rats had lower liver and serum cholesterol levels than meal-fed intact rats and ad libitum-fed adrenalectomized rats. These cholesterol levels were increased with glucocorticoid supplementation. It was concluded that adaptation to meal-feeding involves an adrenal response to the periodic absence of dietary energy intake, and that the degree of involvement of this response is determined by the composition of the diet.


Influence of vitamin B-6 on the renin--angiotensin system in rats.

The effects of treatment with pyridoxine or 4-desoxypyridoxine, a vitamin B-6 antimetabolite, and of vitamin B-6 deprivation on the blood pressure response to renin and angiotensin II and on plasma angiotensin concentration and renin activity were studied in Long-Evans hooded rats in order to compare the effects on these factors of vitamin B-6 excess or vitamin B-6 deficiency. Both pyridoxine and 4-desoxypyridoxine caused a progressively increasing inhibition of the response to renin, which was totally suppressed after 24 days of treatment. They had no significant effect, however, on the basal blood pressure, the response to angiotensin II, plasma angiotensin levels, or plasma renin activity. The vitamin B-6-free diet caused an increase in basal blood pressure of 23 +/- 5 mmHg, over a period of 5 weeks, along with a simultaneous decrease in the response to renin and, though to a lesser degree, angiotensin II. The basal blood pressure remained steady at this level and then decreased again, after the 10th week of deprivation, while the response to renin remained low. Plasma angiotensin levels increased from 0.40 +/- 0.06 ng/ml in control animals to 0.97 +/- 0.06 ng/ml in the deficient rats, and plasma renin activity increased from 5.19 +/- 0.35 to 11.31 +/- 1.56 ng of angiotensin I/ml/hour.


Effect of molybdate on sulfide production from methionine and sulfate by ruminal microorganisms of sheep.

Purified diets containing sodium sulfate and DL-methionine as sole dietary sources of sulfur were fed to fistulated sheep. The effect of dietary sodium molybdate (50 ppm Mo) on the capacity of the rumen microorganisms to produce sulfide from either sulfate or methionine was assayed in the two sulfur diets. Dietary molybdenum significantly inhibited the production of sulfide from sulfate but enhanced significantly the production of sulfide from methionine. The inhibitory effect of molybdenum on sulfide production in vitro and the number of sulfide-producing bacteria present in the rumen of these sheep are discussed in considering the mechanism of the molybdate effect on sulfide production.


Metabolism of [35S]taurine in man.

Taurine metabolism in man was defined by an isotope dilution technique during normal taurine intake (five subjects) or increased taurine intake (two subjects). A tracer dose of [35S]taurine was administered intravenously, and the amount and chemical form of radioactivity were determined in blood, urine, bile, and feces. Analysis of plasma specific activity decay curves indicated that taurine metabolism can be described by two exchangeable pools: a small (2 mmoles), rapidly exchanging pool (t1/2 approximately equal to 0.1 hour); and a large (98 mmoles), very slowly exchanging pool (t1/2 approximately equal to 70 hours). A small amount of [35S]isethionic acid was detected in urine, possibly the result of deamination of taurine by tissues; but otherwise no evidence of tissue biotransformation was obtained. Taurine was excreted predominantly (95%) in urine, about 70% as taurine and 25% as sulfate. The sulfate was considered to be formed in the intestine by bacterial degradation of taurine and then absorbed. Supplemental taurine (given orally) was well absorbed, caused a transient increase in plasma taurine levels, was excreted in urine without equilibration with the slowly exchangeable pool, and caused only a modest increase in total body taurine. Thus, taurine resembles other amino acids in having large tissue pools but differs strikingly in being metabolically inert with an extremely slow turnover rate.


Effects of protein content of diet and cortisol treatment on uptake of arginine by rat liver.

Experiments were conducted to determine whether the rate of entry of arginine into liver varies with changes in dietary protein or in the protein-catabolic state of the animal. It was first established by liver perfusion with [14C]ureidocitrulline that release of arginine by liver is sufficiently small that it can be ignored and that disappearance of arginine from a perfusion medium can be used to measure entry rate. Disappearance rates of arginine were then determined for rats that had been starved of fed either a stock control diet, a 15% casein diet, a 90% casein diet, or which had been injected with cortisol. There was no difference in arginine uptake between the control and 15% casein groups. The high protein group showed a threefold increase in rate of entry of arginine into liver as compared with the control group. Cortisol treatment and 48 hours of starvation also caused a threefold increase in arginine uptake. Cortisol treatment combined with high protein adaptation resulted in a sevenfold increase over controls. It was concluded that rate of entry of arginine into rat liver varies with nutritional and endocrine states.


Increased activity of pyruvate kinase in plasma of vitamin E-deficient rats.

The effect of dietary vitamin E on activities of pyruvate kinase and lactate dehydrogenase was studied in tissues of rats. The activity of pyruvate kinase in plasma of 1-month-old male rats fed a vitamin E-deficient diet for 4 months increased 8.5-fold over that of 45 ppm vitamin E-supplemented animals. Relative to the supplemented group, the enzyme activity increased 23% (P less than 0.001) in red blood cells, was unchanged in liver and lung, and decreased 20% (P less than 0.001) in muscle of vitamin E-deficient rats. The activity of lactate dehydrogenase was not significantly altered by dietary vitamin E in all tissues measured. Similar results were obtained when 2-month-old rats were fed the respective diets for 3 months. The results suggest that vitamine E deficiency in rats may cause muscular damage and release of pyruvate kinase into blood circulation.


Keratitis on exposure to dimethyl phosphorochloridothionate (dmpct).

Six cases of exposure to Dimethy Phosphorochloridothionate (DMPCT) are reported. All patients suffered cornel injuries. Characteristically the corneal lesions (punctate keratitis) became apparent after an interval of at least eight hours. With proper treatment all patients recovered completely with no impairment of visual acuity.


Melanosis coli: studies of the toxic effects of irritant purgatives.

Colonic biopsies from six patients with normal colons and seven patients with melanosis coli were studied ultrastructurally and histochemically for lysosomal enzymes. Anthraquinone purgatives were found to increase the number of macrophages in the connective tissue of the colonic mucosa. In addition, they cause an increase in the intensity of lysosomal activity and an increase in the number of lysosomes in macrophages, Schwann cells and neurones of the submucosal plexus of the colonic mucosa.


An ependymoblastoma of the pons.

A case of ependymoblastoma of the pons in a child is reported, the first so far described in this location. The case adds further evidence for the acceptance of ependymoblastomas as a specific variety of primitive human glioma.


Apocrine metaplasia in cystic hyperplastic mastopathy. Histochemical and ultrastructural observations.

A histochemical and ultrastructural investigation of apocrine cells in the human breast has been carried out. These cells showed strong oxidative enzymatic activity, large numbers of mitochondria and numerous infoldings of the basal plasma membrane. In these features, such cells resemble the normal apocrine gland cells. These observations support the view that this lesion is a metaplastic change in normal breast epithelium.


Biliary atresia and the Dandy-Walker anomaly in a neonate with 45,X Turner's syndrome.

A case is described of a neonate with Turner's syndrome (45,X) whose clinical course was complicated by jaundice. Autopsy findings included intraphepatic biliary atresia, coarctation of the aorta of the infantile type, and the Dandy-Walker syndrome.


Morphological patterns of articular cartilage fibrillation.

The morphology of articular cartilage fibrillation is usually studied in sections cut vertical to the surface. The present study instead concerns the appearances seen when the surface is viewed en face. The study has been made on indian ink preparations of unfixed, hydrated tissue mounted in physiological saline and examined by stereomicroscopy at times 10 while in situ on the bone, and by transmitted light microscopy of tangential surface slices at magnifications up to times 150. The results are consistent with an hypothesis that fibrillation represents mechanically induced focal wear of the tissue. Various sorts of "minimal fibrillation" and other types of surface markings are illustrated. The en face pattern of the cartilage lesions is to some extent influenced by anatomical site, and it is suggested that it is modified by the local biomechanical environment and local character of the cartilage. Some, but not all, of the various patterns show orientation in the sense either of being predominantly unidirectional or of having two major alignments one at right-angles to the other. The differing relationships of this orientation, when present, to the direction of joint movement and to the alignment of the superficial collagen and its tensile strength, are described and discussed.


The development of the human type II pneumocyte.

Portions of lung from 25 human foetuses between 12 and 26 wk of gestational age were examined for ultrastructural changes during maturation of the epithelial cells. In 10 cases type I pneumocytes and in five cases type II cells were differentiated. The changes associated with the formation of lamellar inclusion bodies in type II cells are described. It is concluded that this is a synthetic process in which protein and lipid assembly are important. Changes in glycogen and participation of dense bodies are striking.


Histochemical identification of glycoproteins in pig bronchial epithelium: (a) normal and (b) hypertrophied from enzootic pneumonia.

The glycoproteins in the normal pig bronchial gland are identified by the combined Alcian Blue (AB)-periodic acid Schiff (PAS) technique, with the use of sialidase digestion and AB staining either at pH 2-6 or at pH 1-0. In enzootic pneumonia (produced experimentally by infection with Mycoplasma hyorhinis) the bronchial gland hypertrophies, mucous and serous cells both increase, in number and size; hence the total glycoprotein content of the gland increases.  The distribution of glycoproteins in the hypertrophied gland differs from that in the normal. Quantitative analysis of the mucous cells shows that in the hypertrophied gland the acid glycoprotein is increased relative to the neutral. There is also a relative change in the amounts of sialidase-sensitive sialomucin and sulphomucin; both are significantly increased at the expense of the sialidase-resistant sialomucin. Qualitative analysis of the serous cells shows that in the normal gland most of the glycoprotein is neutral and that the small amount of acid glycoprotein is sialidase-resistant sialomucin. In the hypertrophied gland there is relatively more acid glycoprotein which is either sialidase-resistant sialomucin or sulphomucin; in addition, in pigs with enzootic pneumonia there is an increase in the height of the bronchial epithelium and a depletion in both goblet cell number and glycoprotein content, which latter has more neutral glycoprotein and less acid glycoprotein.


Bone growth kinetics IV: a preliminary investigation on a biorhythm in human osteogenesis.

Multiple doses of oxytetracycline were administered at regular but different intervals to groups of patients undergoin orthopaedic surgery. It was found that doses of the drug were incorporated at bone growth sites most frequently if the intervals between those doses were 3 or 6 days. This suggests a biorhythm in human bone growth with a periodicity of 3 days: this biorhythm may be altered by hormones or drugs.


Experimental paracetamol-induced hepatic necrosis: a light- and electron-microscope, and histochemical study.

Rats were killed at various time-intervals up to 48 hr after a single large dose of paracetamol (3 g per kg) and their livers examined by light and electron microscopy. In general, this revealed glycogen depletion, loss of ribosomes, and cytoplasmic matrix swelling commencing 3-6 hr after administration which in centrilobular hepatocytes progressed to frank coagulative necrosis at 12-24 hr. Midzonal cells showed more prominent aqueous swelling with besiculation of the endoplasmic reticulum, and in some cells, gross hydropic vacuolation.


Leiomyosarcoma of the saphenous vein.

A case of primary leiomyosarcoma of the greater saphenous vein with metastatic spread to the thyroid gland and subcutaneous tissue is described. The literature of saphenous vein leiomyosarcomas is reviewed.


Studies of the responses of basophil and eosinophil leucocytes and mast cells to the nematode Trichostrongylus colubriformis. I. Observations during the expulsion of first and second infections by guinea-pigs.

During expulsion by guniea-pigs of both first and second infections with the intestinal nematode parasite Trichostrongylus colubriformis, increased numbers of basophils and eosinophils were present in the bone marrow and blood. In addition, increased numbers of basophils, mast cells and eosinophils, many possessing reduced numbers of cytoplasmic granules, accumulated at the sites of infection. Blood eosinophil counts, however, did not show significant changes during the early part of a first infection.


Development of the capacity to produce specific antibody to an ingested food antigen in the premature infant.

Thirteen premature infants were given bovine serum albumin, a cow milk protein, by addition to their formula. Serum antibodies to BSA developed in three infants 36-38 weeks' gestation, confirming that exposure to the antigen in the gastrointestinal tract will immunize infants born after 36 or more weeks' gestation. Serum antibodies to BSA, however, were detected in only one of two infants of 35 weeks' and in none of eight infants of 30-34 weeks' gestation. The results show that the capacity to make specific antibodies to BSA develops around 35-36 weeks' gestation, despite the prior appearance of organized lymphoid tissue and independent of antigen exposure.