A comparison of sodium excretion in response to infusion of isotonic saline into the vena porta and vena cava of conscious rats.

1. Indwelling non-occlusive catheters were placed in the vena porta and inferior vena cava of female rats several days before experimentation. Isotonic saline or isosmotic glucose (2% of body wt.) was infused into one vein followed one to several days later with an identical infusion into the other vein of each conscious animal. 2. Significantly higher urine flow and sodium excretion resulted from infusion of isotonic saline (0.5 ml/min) into the vena porta than into the vena cava. Modest prehydration or section of the hepatic branch of the right vagus did not affect the differential sodium response. Changes in endogenous creatinine clearance and potassium excretion were not significantly different for the two routes. Mean values for net peak sodium excretion and contemporaneous urine flow, urinary sodium concentration, and fractional sodium excretion were significantly higher for the portal than for the caval infusion while differences in glomerular filtration rate and filtered sodium load were insignificant. No significant difference in sodium excretion resulted from infusion of isosmotic glucose by the two routes. 3. Compared to the response promoted by the isotonic saline load infused at 0.5 ml/min, the differential response in sodium excretion was prolonged when the same load was infused at 0.375 ml/min. Sodium excretion was not significantly different for the two routes when the same isotonic saline load was infused at 0.75 ml/min. 4. These experiments provide evidence for participation of the liver in the control of sodium excretion and suggest release of a hepatic humoral factor which may be controlled by the duration of exposure of the hepatic circulation to an adequate load of isotonic saline.


Firing rate and size distribution of the hind limb extensor and flexor motoneuronal units.

Axonal spike size of extensor and flexor motoneurones were subjected to statistical analysis. Extensor motoneurones were isolated in decerebrate cats and the flexor motoneurones in spinalized cats. Smallest spikes were due to gamma motoneurones which could be further classified as small, medium and large. Extensor and flexor alpha motoneuronal units were also divided into these three subgroups. Considering the firing pattern and the cell size extensor alpha units were divided into five types: small-tonic, medium-tonic, large-tonic, large-phasic and largest-phasic. Maximum firing rate of extensor alpha units was directly related to the cell size and was distributed between 5-15, 15-20, 25-40 and 35-55 imp/sec for the small-tonic, medium-tonic, large-tonic and large-phasic motoneurones. Stabilized firing rates were distributed between 5-10, 10-15 and 15-20 imp./sec for the small-tonic, medium-tonic and large-tonic motoneurones. Flexor motoneuronal types and their maximum firing rates were as follows: small-tonic (16 imp./sec), medium-tonic (24 imp./sec), small-phasic (37.5 imp/sec), medium-phasic (30 imp./sec), large-phasic (46 imp./sec) and largest-phasic (only one or two impulses). The functional significance of the results was discussed considering the axonal spike size as an index for the cell size.


Inspiratory inhibition and rebound activation elicited by intermittent electrical bulbar stimulation in various states of pulmonary afferent vagal excitation.

In anesthetized rabbits spirogram and diaphragmatic activity were examined during electrical stimulation of regions of the medulla oblongata. The volleys were triggered by the animal's own respiration. 1. One volley of 120 msec duration at 100 pulses p.s., applied during inspiratory, caused an immediate and transient inhibition of the diaphragmatic activity. After the end of the volley and inspiratory rebound appeared: the tidal volume was increased and the inspiration was prolonged by some 150 msec. The respiratory rate decreased. 2. Continuous low or high frequency electrical stimulation of pulmonary stretch afferents caused an inspiratory or an expiratory effect respectively. In both conditions the effects of additional intermittent bulbar stimulation remained essentially unaltered. 3. By means of specially designed spirometer both pulmonary collapse and marked lung distension were produced. At low lung volume collapse afferents were excited. Inspiratory inhibition and rebound activation upon central stimulation persisted throughout the whole range of lung volume investigated; the rebound increase in tidal volume consecutive to the stimulus volley, however, was minimal in extreme lung distension. 4. Results suggest that the stimulation effects were the consequence of manipulation on intrinsic mechansims of the bulbar respiratory centre.


A device to trigger automatically electrical stimulation at different states of in- or expiration on the background of variable lung inflation in the rabbit.

A device is described which permits to obtain a signal at the beginning of in- or expiration respectively. This signal may be used to trigger an electrical stimulator. To permit studies at different states of lung inflation the tracheal cannula is connected to a spirometer circuit. To produce constant positive or negative air pressure this bellows-type spirometer is loaded with exchangeable metal weights. The tracheal pressure is recorded by means of a pressure transducer, the output of which is taken as signal. The device allows accurate compensation of the DC-component of the transducer output resulting from spirometer operation at a maintained positive or negative pressure.


Effect of increased blood fluidity through hemodilution on coronary circulation at rest and during exercise in dogs.

Coronary flow and myocardial oxygen consumption were measured in conscious dogs at rest and during two levels of submaximal treadmill exercise (3 and 7 km/h at 15% grade, respectively) during adaptation to progressive hemodilution with dextran 60. At rest coronary flow increased to more than seven-fold with diminishing hematocrit to 12.5% in order to cover myocardial oxygen consumption which increased from 6.5 +/- 0.3 ml/min with 100 g at hematocrit 47.5% to 13.5 +/- 0.8 ml/min with 100 g at hematocrit 12.5%. The dilatory capacity of the coronary vessels, estimated from the reactive hyperemia after a 12 sec occlusion of the left circumflex coronary artery, dropped from 602% at control to 45% at lowest hematocrit levels. During the superimposed stress of exercise coronary flow and myocardial oxygen consumption increased further, so that the dilatory capacity of the coronaries was exhausted at hematocrit levels between 16 and 22%. Myocardial oxygen consumption per unit of oxygen delivered to peripheral tissues increased substantially with progressive hemodilution. In the presence of the reduced arterial oxygen content the augmented myocardial oxygen demand limits the overall adaptability to hemodilution by an exhaustion of the coronary dilatory capacity.


Effect of increased blood fluidity through hemodilution on general circulation at rest and during exercise in dogs.

During progressive normovolemic hemodilution with dextran-60, circulatory functions (cardiac output, oxygen delivery to tissues, arterial pressure and mixed venous oxygen saturation) and total body oxygen consumption were studied in conscious dogs at rest and during two levels of submaximal treadmill exercise. At rest, cardiac output rose continuously with progressive hemodilution. This increase, however, was not sufficient to compensate for the reduced arterial oxygen content. Consequently oxygen delivery fell significantly from 23.3 +/- 1.8 ml/min with kg at hematocrit 47.5% to 15.7 +/- 0.9 ml/min with kg at hematocrit 12.5%. The constant oxygen consumption was maintained by a simultaneous increase in oxygen extraction from blood. During the superimposed stress of exercise, a constant oxygen consumption was maintained between hematocrit ranges of 50 to 15 or 25%, respectively. Again, the increase of cardiac output due to hemodilution did not compensate for the reduced arterial oxygen content and consequently oxygen extraction rate was increased. These data demonstrate that at rest (and even more during submaximal treadmill exercise) the reduced whole blood viscosity or improved fluidity during hemodilution does not initiate an increase in cardiac output that is sufficient to maintain a constant oxygen delivery to the tissues.


Properties of mechanosensitive neurons within Auerbach's plexus of the small intestine of the cat.

Three different kinds of mechanosensitive neurons were detected by direct electrical recording from Auerbach's plexus. Neurons classified as fast-adapting mechanoreceptors discharged spikes at the onset of stimulation, and the discharge stopped during a sustained stimulus of constant intensity. Slowly-adapting mechanoreceptors maintained during sustained stimulation, a steady discharge at a frequency that was a direct function of the intensity of the stimulus. Tonic type neurons responded to mechanical stimulation with a prolonged train of spikes which had a consistent pattern from preparation to preparation. Once the tonic-type cells were triggered, the discharge followed a characteristic time course that was unchanged by further increase or decrease in stimulus intensity. Tonic-type neurons are probably not first order sensory neurons, but they may be activated by input derived from primary mechanoreceptors. Frequency of discharge of slowly-adapting mechanoreceptors was increased by histamine. This appeared to be secondary to histamine-induced contractile activity of the musculature.


Colostral transfer of immunity to Haemophilus parahaemolyticus in pigs.

Complement fixating antibodies for Haemophilus parahaemolyticus were shown to be transferred from immune sows to their offspring. Colostrum-fed 4-day-old piglets from immune sows resisted intranasal inoculation whereas their littermates, fed on cows' milk, were fully susceptible to the infection. Piglets inoculated later in the suckling period (3 to 8 weeks after birth) when their serumtiters had declined to very low levels, showed some degree of resistance, but the infection was not eliminated from the mucous membranes of the respiratory tract. In chronically infected breeding herds piglets are usually affected during the later part of the suckling period and clinical symptoms are often vague. Though a positive titer is indicative of resistance the results presented above show that protection is usually not complete. Further studies are required to ascertain whether the results obtained here are applicable in a rational control.


Amino acid reabsorption in the rat nephron. Free flow micropuncture study.

The concentration of nine endogenous free L-alpha-amino acids (ALA, LEU, ILE, PHE, TYR, LYS, GLU, PRO, GLY) and of taurine were determined simultaneously along the nephron of the rat kidney using free-flow micropuncture techniques without altering plasma amino acid concentration or kidney function. The amount of each amino acid was determined after dansylation (14C-labelled dansyl-chloride) in the micropuncture sample followed by thinlayer chromatography. The main site of reabsorption is the proximal tubule. After 15-20% of the proximal tubule length the bulk of reabsorption has taken place (18.9 plus or minus 3.4% S.E. of the filtered load remaining). Net reabsorption continues to a small but significant extent along the distal nephron (disal tubule and collecting duct). Reabsorption of taurine is less rapid (% remaining of filtered load at the early proximal tubule 37.0 plus or minus 4.6%). The transtubular concentration ratio of all amino acids except taurine follows a homogeneous course. Under the experimental conditions of this study no distction with respect to different systems of reabsorption "neutral", "basic", "acidic", "imino-glycine") could be made.


Selection for mating ability in Japanese quail.

Results are presented for a replicated mass selection experiment for high and low cumulative number of completed matings. Through six generations of selection heritabilities of the selected trait averaged .07 for the high lines and .25 for the low lines. No correlated responses were noted for body weight at either 4 or 8 weeks of age, whereas the relationships of the selected trait with size of the cloacal gland and relative aggressiveness were positive.


Isolation of rapidly labeled RNA from mouse L-cells using cupric sulfate.

Cultured mouse L-cells, pulse labeled for 5 min with 3H-uridine, were gently suspended in 0.5mM cupric sulfate and 0.5% sodium dodecyl sulfate at 4 degrees C and treated with cold phenol. Only the RNA, containing less than 1% DNA, was extracted by this procedure. The rapidly labeled ribosomal RNA precursors (44S, 34S) and cytoplasmic 8S RNA showed specific activities higher than that of tRNA and were present in the RNA fraction insoluble in 2M NaCl.


An antigenic antimorphogenetic bone hydrophobic glycopeptide (AHG).

A hydrophobic glycopeptide, isolated from fresh marrow-free cortical bone of the rat, extinguished the bone morphogenetic response of insoluble bone matrix gelatin which otherwise invariably produces new bone from migrating mesenchymal cells after implantation in muscle of the rat. Incubation of the 10 to 100 mug of the glycopeptide per milligram of bone gelatin in phosphate or Tris-HCl buffer, pH = 7.4, for 24 hours recombines the hydrophobic polypeptide and gelatin. Incubated with doses of 50 to 100 mug, implants of gelatin in Sprague-Dawley recipients are rapidly resorbed by a lymphocyte-plasma cell-macrophage infiltrate without developing any new bone. With 10 to 20 mug, infiltrate appears and bone develops inversely in proportion to the dose. Bone develops at all dose levels only when bone matrix gelatin and glycopeptide were prepared from an inbred strain of Lewis rats and recipients were of the same strain, and thereby suggests that only allogeneic AHG, produces an antigenic antimorphogenetic resonse. The glycopeptide was isolated from bone together with lipids and other hydrophobic proteins or polypeptides by chloroform-methanol (1:1) extraction and further purified by chromatography on ion-exchange columns and molecular sieves. The molecular weight established by Sephadex G-100 filtration and by calibrated dialysis is about 5000 daltons. Analysis of the biologically active fraction shows 75% of proteinaceous material and close to 25% carbohydrate with trace amounts of hexosamines and sialic acid. Amino acid analysis shows high levels of alanine, valine and leucine in comparison to other chloroform-methanol extractable but immunogenically relatively-inactive fractions.


An accurate slicer of disc acrylamide gels devised by simple modification of a density gradient fractionator.

A commercially available density gradient fractionator has been modified in a simple and inexpensive way to yield a device for accurately slicing disc acrylamide gels. Attractive features of this device include convenience of operation and the capacity to easily vary thickness of the gel slice.


Modulation of the uptake and retention of estradiol-17beta in the ovine corpus luteum by luteinizing hormone.

The uptake and retention of 3H-estradiol by the ovine corpus luteum (induced by superovulation) was maximal through days 8-12 of the cycle with little or no uptake and retention during luteinization or regression. LH, but not FSH or prolactin, inhibited the uptake and retention of estradiol via stimulation of progesterone synthesis.


The study of some compounds biosynthesized by Naematoloma fasciculare (Huds ex Fr.) P. Karst. Part I. Analysis in vitro.

From the explantats of the fruitbody of Naematoloma fasciculare (Huds ex Fr.) P. Karst., xylophilous macromycete, the mycelial culture was obtained on the maltose agar with addition of thiamine. The submerged shaken culture yielded the growth of the mycelium six times higher than the surface culture. The material obtained from the mycelial cultures was investigated chromatographically (PC, TLC) on the presence of carbohydrates, sterols and nitrogen compounds. There was no difference between the compounds biosynthesized in both culture in vitro.


Similarity in cns sensitivity to hexobarbital in the rat and mouse as determined by an analytical, a pharmacokinetic, and an electroencephalographic measure.

Sensitivity of the central nervous system (CNS) to the hypnotic effect of hexobarbital was assessed by analytical, pharmacokinetic, and electroencephalographic techniques in male and female rats and in mice of both sexes by the first two techniques. These experimentally and conceptually diverse measures yielded strikingly similar estimates of CNS sensitivity to hexobarbital which was independent of both species and sex, while well known species ans sex (rat) differences in duration of response to hexobarbital were demonstrated.


Intraspecific aggressiveness after lesions of midbrain raphe nuclei in rats.

Serotonin-depleting lesions of midbrain raphe (extensive lesions located within dorsal and partly median raphe muclei) induced intraspecific agressiveness in grouped Wistar male rats but failed to increase mouse-killing behaviour. Rats which had lesions in the lateral midbrain did not display intraspecific aggression nor mouse-killing activity. These animals showed unchanged levels of both serotonin and noradrenaline in the forebrain.


Improved automated apparatus for recording rotation (circling behavior) in rats or mice.

An improved automated apparatus for measuring rotation (circling behavior) is described. The apparatus may be designed for either mice or rats. The logic circuit differentiates between complete 360 degrees rotations and incomplete oscillatory turns; preliminary data indicate that this distinction has functional significance.


Neonatal hormone experience and adult lordosis and fighting in the golden hamster.

Androgenization by testicular secretions or exogenous testosterone propionate (TP treatments administered 24-48 hr post partum) suppressed sexual receptivity in the golden hamster. In response to prolonged adult estradiol benzoate (EB) treatment, gonadectomized normal females and neonatally castrated males exhibited significantly longer total lordosis durations than normal male or neonatally TP-treated (20 mug or 200 mug) females. These results suggest that one aspect of androgen-induced masculinization in the hamster involves reduced estrogen sensitivity. Responses to sequential EB followed by progesterone treatment were also lower in the androgenized groups. Neonatally castrated males did not differ significantly from normal females in their lordosis behavior. Irrespective of adult hormone treatment, androgenized animals fought more than normal females or neonatally castrated males. A genital mask was used to reduce sex differences in peripheral stimulation during testing.


Effects of the lesion of the postcommissural part of the septum on the behavior of the rat.

The effects of the lesion of the postcommissural part of the septum on behavior of the rat has been studied. Results may be summarized as follows. An increase in the exploratory behavior in the open field which decreases rapidly; a decrease in the number of defecations in this test and a decrease in time leaving a dark environment for exploration. In the shuttle box test, no facilitation of the acquisition, but a permanent and quite significant increase in the intertrial activity has been found. We conclude that the lesions tend to decrease the emotivity of the subjects. An interpretation on the basis of the species -- specific defensive reactions explains the transitory and permanent effects of the lesions on the spontaneous activity.


Postpartum aggression in mice: inhibitory effect of estrogen.

The daily administration of estradiol benzoate (EB) to lactating mice that previously exhibited aggression toward a male intruder reduced the amount of time subsequently spent fighting as well as the total number of animals that fought. EB treatment also depressed body weight of the dams and their lactation performance. Daily progesterone treatment only reduced lactation performance.


Dominance behavior: a phylogenetic analysis in the mouse.

Tube-dominance behavior differed significantly in C57BL/6By and BALB/cBy mice. Evaluation of these two inbred strains, and their recently developed recombinant inbred strains permitted the derivation of an hypothesis regarding possible genetic control of this behavior in mice. The results were analyzed by means of patristic matrices with accompanying phylogenetic tree analysis that marks the first occasion that such analysis has been used for a behavioral trait. Based on the data obtained and the statistical analyses and groupings of the various strains, the most satisfactory hypothesis that can be proposed at this time is one which assumes that dominance behavior, as measured in this experiment, is influenced genetically by at least 3 loci. Attempts to link these loci were not successful.


Recovery of mating behavior in the female rat following VMH lesions.

On the day of proestrus, female rats were given large electrolytic lesions aimed at the ventromedial nucleus of the hypothalamus (VMH). Following a postoperative period of extended diestrus the vaginal smears showed irregular periods of vaginal cornification with a tendency toward prolonged periods of cornified smears. Sexual receptivity, measured in terms of the lordosis-to-mount ratio (L% = L/M X 100) was low on the evening of the first postsurgical proestrus, but improved markedly in subsequent mating sessions. Although the lordosis response was present, the intromission frequency remained below that observed during mating sessions with control females. Findings at autopsy together with the prolonged periods of vaginal cornification suggest that VMH lesions result in blocked or delayed ovulation. The behavioral data contradict previous reports of blocked mating behavior in VMH females based upon indirect measures of receptivity, i.e., the presence of vaginal plugs or sperm on the morning following overnight caging with sexually active males.


Retrograde amnesia induced by hypoxia and electroconvulsive shock in two rat strains.

Hypoxia or electroconvulsive shock (ECS) was administered to two strains of rats following one trial passive avoidance training. ECS produced retrograde amnesia in the Blue Spruce Farms Long Evans hooded rat when administered within 10 sec after training and in the Charles River albino rat when administered within 75 sec after training. Hypoxia was effective in producing retrograde amnesia when administered up to 40 min after training in the hooded rat but only when administered between 20 and 30 min after training in the albino rat. The importance of strain variability is discussed.


The effects of chloridazepoxide on avoidance performance of mice subjected to undernutrition or handling stress in early life.

This experiment compared the effects of (u) "early undernutrition" by rearing in large litters and (ii) an early handlin g stress, on avoidance learning in Swiss white mice. The two treatments, the first leading to permanent physical stunting and the second not, had similar and additive detrimental effects on avoidance performance. Treatment with  the minor tranquillizer Chlordiazepoxide improved performance in all groups but had a proportionately greater effect on previously undernourished, handled mice. Thus the poor avoidance performace of mice reared in large litters appears to be largely independent of the growth stunting effect and more closely related to an elevated stress response produced by stress in early life.


Conditioned learning in young rats born of drug-addicted parents and raised on addictive drugs.

Ratlings born of six drug-addicted and a control group of parent rats were raised under the influence of the same drugs administered in drinking water. They were trained in a conditioned avoidance paradigm (CAR) from the 7th week when the drugs were withdrawn except in two subgroups of flurazepam and morphine. The growth rate was not appreciably impaired except for temporary slowness in morphine and alcohol-raised rats; it was faster in phenobarbitone and meprobamate-raised rats. The CAR-acquisition rates of the treatment groups were quite close and parallel to that of the controls except for the morphine, meprobamate, medazepam and the two drug-trained subgroups; whereas, the rats raised on low-dose morphine showed a faster than control acquisition rate. No evidence of state-dependent learning was obtained from this study.


Influence of response topography on the effect of apomorphine and amphetamine on operant behavior of pigeons.

Key-pecking and treadle-pressing behavior were maintained in five pigeons by a mult. FI5 key FI5 treadle schedule of food presentation. Dose-effect curves for apomorphine and amphetamine on overall rates of responding in both F1 componenets of the multiple schedule were determined. Effective doses of apomorphine caused dose-dependent decreases on treadle-pressing rates in all animals. Similarly, key pecking rates were decreased by increasing  doses of apomorphine in two of the five pigeons. However, dose-dependent increases in key-pecking rates were caused by apomorphine in the other three birds. In this group of pigeons, the mean key-pecking rate was increased to over 500% of the control rate by the dose of 1 mg/kg of apomorphine. Observation of the animals under the effect of apomorphine showed continuous pecking at the operative key in these three animals while the other two pecked at different places of the floor and walls of the experimental chamber. Appropriate doses of amphetamine caused rate-increasing effects on key-pecking as well as treadle-pressing rates of all pigeons. These results suggest that the increases in key-pecking rate caused by apomorphine in some pigeons in a conventional operant situation due to the orientation of the drug-induced stereotyped pecking toward the response keypecking, as a consequence of the topographic compatibility between this behavioral effect of apomorphine and the operant selected for study.


Pharmacological evidence for cerebral dopamine receptor blockade by metoclopramide in rodents.

Metoclopramide antagonises apomorphine-induced stereotypy in rats (ED50 1.5 mg/kg), apomorphine reversal of reserpine-induced locomotor suppression in mice (50% inhibition produced by 17 mg/kg), and apomorphine- or amphetamine-induced turning behaviour in mice with unilateral lesions of the striatal dopaminergic nerve terminals (ED505.0 and 4.0 mg/kg respectively). Metoclopramide resembles pimozide in all these respects and appears to be a relatively potent antagonist of striatal dopamine receptors. Yet metoclopramide, in anti-emetic doses, has no effect on disability in Parkinson's disease or on the therapeutic benefit of L-Dopa and L-Dopa dyskinesias.


Disruption of state-dependent learning (memory retrieval) by emotionally-important stimuli.

State-Dependent Learning (SDL) occurs when a response learned in a particular drug stste does not transfer to another drug state. SDL was demonstrated and disrupted in a modified T-maxe escape learning task, using male hooded rats. SDL groups were trained each day in one drug state (either Librium, 40 mg/kg or sterile water) and then given non-shock test trials in both drug states. SDL Ss showed drug-dependent retention since they turned randomly in opposite-state test trials and significantly above random level (P greather than 0.02) when in the training drug state. For the Transfer Ss, 1k Hz tone was simultaneously paired with foot shock in training and continued to be sounded on every non-shock test trial. Transfer Ss turned in the training direction regardless of drug state. Drug-dependence in the SDL groups and transfer in the Transfer groups were also demonstrated in response latencies. The tones were emotional memory prompters initiating some process that  mediated transfer between drug states. The theoretical importance of these results were discussed in relation to energizing and directing functions of emotions and symmetrical and asymmetrical transfer.


The inhibition of A and B forms of MAO in the production of a characteristic behabioural syndrome in rats after 1-tryptophan loading.

1-Tryptophan was administered to rats pretreated  with selective inhibitors of the A and B forms of MAO deprenyl, a selective inhibitor of MAO-B, produced minor changes in behaviour and in the concentrations of apparent 5-HT and 5-HAA in brain. High doses of clorgyline, a  selective inhibitor MAO-A, produced a characteristic stereotyped syndrome of hypermotility and tremor as well as an increase in apparent 5-HT and a decrease in apparent 5-HIAA in brain. Small doses of deprenyl and clorgyline in combination, but not singly, produced maximal effects on behaviour as well as on the concentrations of apparent 5-HT and 5-HIAA in brain. Maximum behavioural and biors before the other. It is concluded that the syndrome may be dependent on the formation of an N-substituted derivative of 5-HT which is at least partly deaminated by MAO-B. Alternatively, the syndrome may be dependent on a sufficiently high concentration of 5-HT in a special compartment where it is partly deaminated by MAO-B.


Effect of sensory stimulation on the potency of cataleptogens.

Pressures of up to 100 mm Hg applied to the mouse tail caused marked enhancement of the cataleptogenic potency of morphine, haloperidol and arecoline. Visual and auditory stimuli of moderate intensity also enhanced morphine catalepsy. Thus potentiation of cataleptogens by alteration of sensory input appears to be a fairly general phenomenon. The significance of these findings is discussed.


Absence of interaction between delta9-tetrahydrocannabinol (delta-THC) and cannabidiol (CBD) in aggression, muscle control and body temperature experiments in mice.

In this report we give the results of some experiments on the effects of the hashish constituents delta9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on mice. THC produced a dose dependent depression of aggression in isolated mice and a dose dependent depression of body temperature in group caged mice. The drug did not alter motor co-ordination. CBD showed a small, not significant influence on aggressiveness, and no in fluence on body temoerature and muscle control. The dame experiments were carried out with combinations of THC and CBD in several dosages. In these experiments no interaction between both compounds was seen. This means that there can only be an additive action and not potentiation in the pharmacological sense. It also means that the in vitro inhibition by CBD of the drug metabolizing enzymes, responsible for biotransformation of THC. is not strong enough to result in changed effects of THC in the living animal.


Neuroleptic-induced hypersensitivity of striatal dopamine receptors in the rat as a model of tardive dyskinesias. Effects of clozapine, haloperidol, loxapine and chlorpromazine.

The present study has compared the abilities of clozapine, haloperidol, chlorpromazine and loxapine to induce dopamine (DA)-receptor hypersensitivity in rats, as measured by the apomorphine response after withdrawal of the antipsychotic drugs. Haloperidose during 1-2 weeks after withdrawal. Clozapine, given prior to apomorphine, reduced the responses of the haloperidol and loxapine groups to the control level. The effects of haloperidol and clozapine were quantified in rats with unilateral striatal lesions. Biochemical investigations showed that tolerance developed to the increase in striatal homovanillic acid (HVA) after chronic treatment with haloperidol, chlorpromazine and loxapine, whereas clozapine (20 mg/kg p.o.) failed to affect the HVA content, and no tolerance developed to the increase seen at 80 mg/kg. Cross-tolerance to the rise in HVA was seen with haloperidol, chlorpromazine and loxapine, but chronicc pretreatment with clozapine failed to affect the rise in HVA induced by a singel dose of the former compounds.


The interaction of post-weaning housing conditions and prenatal drug effects on behaviour.

Offspring of rats given oral doses of imipramine (5 mg/kg) from 14-2f gestation were reared, after weaning, in deprived or enriched environments. When tested in both a Henderson-type maze and a swimming maze no behavioural effects due to prenatal drug exposure were observed when the Ss were reared in a deprived environment. When the Ss were reared in an enriched environment the maze performance of those animals which had been exposed to imipramine or vitamin-A was significantly inferior to that of the control animals. The implications of these findings are discussed with respect to environmental interaction with prenatal drug effects on behavior.


Effects of cannabis resin on social behaviour in the laboratory mouse.

The effects of several dose levels of cannabis have been studied by an ethiological analysis of encounters between male mice injected with the drug and partners injected with Tween-saline. The duration of immobility was directly related to the logarithm of the dose of cannabis given. The ratio of flight in the treated animals to aggression in those mice with which they were paired showed a progressive increase as the dose of cannabis was raised from 4-50 mg/kg. A straight line relationship was found to exist between the logarithm of flight/aggression and logarithm of the dose of cannabis administered. Non-social activity and social investigation were decreased by the administration of cannabis; this was due to the time spent by the treated animals in immobility. Aggression was not significantly altered. Many mice given doses of 25-100 mg cannabis/kg showed an ataxic gait and the Straub tail reaction.


The effects of azaperone, a sedative neuroleptic of the butyrophenone series, on dominant-subordinate behaviour in wistar rats competing for food.

The effects of azaperone, a sedative neuroleptic of the butyrophenone series with outstanding anti-aggressive and anti-shock activity on dominant-subordinate relationship in pairs of rats, competing for food, are described. Treating the dominant rat of a pair with azaperone, a dose related weakening (at 0.16 and 0.31 mg/kg) and reversal (at 0.63 mg/kg and above) of the initial strong dominant-subordinate relationship is demonstratedmat 5 mg/kg the dominant-subordinate reversal is complete until the end of the test session. Dominant-subordinate relationships are modified by azaperone at doses far below those inducing gross behavioural changes. The present results point at a normalizing effect of azaperone on social interaction through inhibition of aggressive responsiveness.


The behavioral pharmacology of butaclamol hydrochloride (AY-23,028), a new potent neuroleptic drug.

Butaclamol hydrochloride (AY-23,028) is a member of a new chemical class for which antipsychotic activity in humans has recently been demonstrated. The compound antagonized amphetamine-induced stereotyped behavior in rats, amphetamine toxicity in aggregated mice and apomorphine-induced emesis in dogs. It depressed both discriminated avoidance and continuous lever-pressing behavior in rats and inhibited ambulation and rearing in the open field. At higher doses, AY-23,028 induced catalepsy. Adrenergic blocking activity, measured by the antagonism of epinephrine-induced mortality, was weak. These pharmacological actions are characteristic of neuroleptic drugs. In the dose range where the aforementioned effects were observed AY-23,028 did not antagonize either the tetrabenazine-induced ptosis or the tremorine syndrome and did not cause either hypothermia or ataxia. The potency and onset of action of AY-23,028 were comparable to those of fluphenazine but AY-23,028 was of longer duration. The results are discussed in relation to current concepts of neuroleptic mechanisms.


Levels of pyridoxine and susceptibility to electroconvulsive and audiogenic seizures.

The effects of pyridoxine deficiency and the administration of supplemental vitamin B6 on audiogenic and electroconvulsive seizures were studied in two inbred strains of mice and their F1 hybrids. Pyridoxine deficient diets increased seizure risk, whereas supplemental vitamin B6 protected these animals against seizures. Penicillamine and thiosemicarbazide, at doses which lowered brain levels of pyridoxine by only 10%, increased seizure risk. Diets deficient in zinc and copper did not alter susceptibility to either audiogenic or electroconvulsive seizures. DBA/2J mice, genetically susceptible to audiogenic seizures, have the same endogenous levels of pyridoxine in the brain as do C57Bl/6J mice, which are resistant to audiogenic seizures.


Enhancement of acquistion and performance of level-pressing behavior in rats by an experimental diet.

Rats given diets containing jack bean had superior performance during learning and testing of level pressing compared with rats given control diets. To evaluate the factors which might have contributed to the differences in their performance, the testing conditions, testing schedules, and the reinforcement were varied. The results strongly suggested that the rate of learning depended largely on factors inherent within the individual animals. The rats preferred the reinforcement, Noyes pellets, to diets containing jack bean. Therefore the superior performance of rats given diets containing jack bean could be, to a certain extent, due to their motivation to lever press for Noyes pellets. However, there was also evidence suggesting that other factors in jack bean enhanced the behavioral performance of rats when water droplets were used as the reinforcement.


Radiotherapy for pure seminoma of the testis.

Testicular tumors initially diagnosed as pure seminoma were irradiated following orchiectomy in 141 patients. Analysis of treatment failures reveals that (a) 2500 rads is adequate for elective irradiation and 3500 rads for small to moderate-size metastases; (b) elective irradiation of the mediastinum and left supraclavicular area is not indicated for Stage I, but is for Stage II; (c) patient with bulky retroperitoneal disease should be treated initially through total abdominal portais followed by additional treatment through reduced fields; and (d) presence of embryonal carcinoma, teratocarcinoma, or choricarconoma should be considered when regression is poor.


Aggression in mice after p-chloroamphetamine.

Two or 3 days after a single high-dose (20 mg/Kg) of p-chloroamphetamine (PCA) aggression was reliably observed in male mice. This agression was not produced when the same dose of d-amphetamine was injected or when PCA was injected one hour before testing. However, PCA produced an increase in locomotor activity one hour, but not 24 hours, after injection.


Male mouse aggression as a pharmacologic model.

At 5 to 8 months of age the fighting and tail-rattling of male Marsh mice during paired confrontations was significantly greater for isolated than for mice prehoused in groups of males or in groups of one male with females. The differences were not significant for treatment effects tested in a similar manner with mice 11 to 12 months of age. At 5 months of age, mounting behavior of pregrouped males on paired confrontation was significantly less than that of isolated males. Paper towels instead of pine shavings for bedding abolished test-fighting for isolated mice. In any model with randomly sampled groups, an inherently highly aggressive mouse (killer) required to be eliminated from the grouped series, is not detected in the isolated series. These considerations challenge the use of isolated male mice as a pharmacologic model for evaluating behavior-modifying drugs. A four-fold difference in the area of prehousing cages of isolated males did not influence aggressive behavior. Fights correlated with tail-rattling; r equals 0.93 over the 14 series studied.


Quantitation of physical dependence in mice by naloxone-precipitated jumping after a single dose of morphine.

Jumping behavior in mice was precipitated by naloxone after single doses of morphine. The time-effect curves showed that this jumping behavior was delayed compared to the ability of morphine to inhibit writhing  and to increase locomotor activity. This dissociation suggests that the jumping response is a true measure of physical dependence rather than the result of a stimulant effect of morphine in the presence of naloxone. The minimum dose of morphine needed to initiate measurable physical dependence fell within the analgesic range. With a constant dose of morphine, the frequency of jumping was directly related to the dose of naloxone employed. The ability to follow the initiation of physical dependence might be useful in conjunction with receptor and neurohumoral studies to uncover the basic mechanisms involved.


Effect of anti-obesity drugs on lipase activity in vitro.

Chlorphentermine, fenfluramine and dexamphetamine have a pronounced stimulating effect on lipolysis as determined by the action of mouse pancreas lipase on the dilauric (didodecanoic) acid ester of fluorescein. Diethylpropion and phendimetrazine have a comparatively minor effect.


Simplified direct radioimmunoassay method for measuring carcinoembryonic antigen.

The radioimmunoassay for carcinoembryonic antigen as usually carried out is an involved, time-consuming procedure complicated by the use of a dialysis step to remove perchloric acid from an extract of the sample. A simplified direct assay for the antigen in serum or plasma is reported here. It is evaluated in comparison with our earlier method which was done using perchloric acid extraction of the samples. The results of the simplified method compare favorably with those of the indirect method.


Effects of naloxone subcutaneous pellets on relapse to morphine self-administration in post-addict rats.

Female Sprague-Dawley rats were prepared with chronic cortical and muscle electrodes and i.v. cannulae. They were administered morphine by i.v. injections, then trained to lever press for i.v. self-injections of morphine (10 mg/kg) to maintain dependence, and subsequently withdrawn for two weeks. At this point, one or two pellets of naloxone base (100 mg) or placebo pellets were implanted subcutaneously. The rats were then returned to the experimental cages and allowed to self-administer morphine or isotonic saline. Rats that were implanted with two 100 mg naloxone pellets did not relapse to morphine self-injections. Although some of the rats implanted with one 100 mg pellet also failed to relapse to morphine, the remainder increased their lever pressing and morphine intake sufficiently to overcome the antagonist effect of naloxone and to reestablish dependence. Rats implanted with placebo pellets and given access to morphine reestablished lever pressing, while those given access to isotonic saline extinguished their lever pressing. These findings demonstrate the ability of the narcotic antagonist, naloxone, to suppress relapse to morphine in post-addict rats.


Production and characterization of antibodies to meperidine.

A mepridine-bovine serum albumin (Mep-BSA) conjugate with 15-20 moles of meperidine per mole of BSA was synthesized and characterized. Rabbits immunized with Mep-BSA produced antibodies that were assayed utilizing saturated ammonium sulfate to separate 3H-meperidine (3H-M) bound to antibody from free 3H-M. Antibody specificity was assessed by competitive inhibition studies. The nanomoles of inhibitor required to decrease the binding of 3H-M by 50% were: meperidine .046; meperidine acid, 3.2; alphaprodine, 7.8; dextromethorphan, 20; codeine, 50; and morphine 55. The sensitivity of the assay is approximately 30 ng/ml; sufficient for pharmacokinetic studies of the disposition of meperidine in man.


Alteration of L cell growth by antibody-stimulated incorporation of radioactive nucleosides.

Radioactive nucleoside incorporation into mouse L cells was stimulated by exposure of the cells to rabbit anti-L cell antibody. Use of nucleosides of high specific radioactivity permitted a selective reduction of replication of antibody-treated cells as compared to control cells. The mechanism most likely involves radioactive damage of nuclear contents and DNA.


Comparative studies of the production of antibodies to angiontensin I.

Antibodies to angiotensin I-BSA were produced in two different animal species to compare their specificity, binding capacities, titers and costs. Also, the antibody response over substantial intervals of time following comparable immunization in different species was studied.


Humoral immune system activity in inflammatory bowel disease.

In vivo activation of complement components C3 and GBG as revealed by crossed immunoelectrophoresis reflects humoral immune system activity in disease. These methods have been applied to a material of 25 patients with ulcerative colitis (UC) and 29 patients with Crohn's disease (CD). Signs of activity in the complement sequence were observed in approximately half the patients of both categories. Fifty blood samples from 30 healthy controls were all negative. The presence of complement activation was correlated with disease activity in both groups, and in patients with CD this could also be shown in longitudinal studies in single patients. In UC complement activation was correlated with the extent of the disease process. The serum levels of factors C4, GBG, and C3 in the patient groups did not differ significantly from those found in the normals.


Thrombotic thrombocytopenic purpura in childhood.

A survey was conducted among 46 pediatric institutions in the United States and Canada to evaluate the presentation, therapy and survival of children with thrombocytopenic purpura (TTP) seen since 1960. TTP is an uncommon disease in the pediatric age group, and the clinical and pathologic findings in adults and children are almost identical. It can be distinguished from haemolytic uraemic syndrome in that it usually occurs in older children, the renal disease is milder, and the central nervous system symptoms appear to be related to vascular occlusive disease, and not to the complications of severely compromised kidneys. Appropriate biopsy specimens which reveal typical widespread hyaline occlusion of arterioles may confirm the diagnosis. Combinations of corticosteroids, splenectomy, and heparin have been used as therapy. Prognosis has improved, and is probably related to improved supportive care.


Destruction of dextran-coated target cells by normal human lymphocytes and monocytes. Induction by a human anti-dextran serum with IgG antibodies restricted to the IgG2 subclass.

A human anti-dextran serum, EAK, with IgG antibodies restricted to subclass IgG2, was tested for its capacity to induce lysis of dextran-coated chicken erythrocytes by normal human lymphocytes or monocytes. Another human anti-dextran serum, RGM, with most antibodies belonging to sublass IgG1, and a hyperimmune rabbit anti-dextran serum were used for reference. In lymphocyte-mediated erythrolysis, serum EAK gave rise to 51-Cr release varying from 20% to 80% in different experiments. The hyperimmune rabbit serum was 100 to 1000 times more active, whereas serum RGM was consistently negative. These results correlated well with the concentration of anti-dextran antibodies in these sera. In monocyte-mediated erythrolysis serum EAK had a somewhat higher titer than in lymphocyte-mediated lysis, and serum RGM had a weak but significant activity at low dilutions. Serum EAK also induced erythrophagocytosis by monocytes. Ultracentrifugation did not significantly decrease the inductive capacity of this serum. The results show that antibodies of human sublass IgG2 are efficient inducers of effector functions in both lymphocytic and monocytic cells. Myeloma proteins of the four IgG subclasses were tested for inhibitory capacity in lymphocyte- or monocyte-mediated erythrolysis. Either serum EAK or the rabbit reference serum was used for induction of erythrolysis. Individual myeloma proteins within and between the subclasses varied considerably in inhibitory power. However, whereas IgG1, IgG2, and IgG3 proteins inhibited lymphocyte-mediated erythrolysis induced by either type of antiserum, the two IgG4 proteins tested were essentially negative. These results suggest a lack of specificity of the Fc receptor for subclasses IgG1, IgG2, and IgG3 in both heterologous and homologous inhibition. In monocyte-mediated erythrolysis, IgG1 and IgG3 were strong inhibitors, whereas inhibition by IgG2 and IgG4 was weak and inconsistent. This pattern was seen regardless of whether and inducing antiserum was of rabbit or human origin. Similar results were obtained in monocyte-induced erythrophagocytosis induced by serum EAK. These and previous results suggest that effector cells of the lymphocytic (K cell) variety have Fc receptors different from those of monocytic cells. However, the basis for the differences observed in the inhibition tests remains to be elucidated.


[Our first clinical experiences with chemically modified heteroplastic arterial transplants from cattle and calf carotid arteries].

In an 18-month period 22 chemically modified bovine arterial heterografts have been implanted in 21 patients. 1 aorto-profundal and 2 iliaco-femoral bypasses have remaint. The overall success rate was influenced by negative patient selection at the outset of the study. The longest follow-up period for a patent femoro-popliteal bypass has been 12 months. The grafts were initially processed by the method of Rosenberg, but there have been decisive improvements and since 1974 nonantigenic grafts of varying length and width have been available. Their strength and density are good and their operative handling excellent. The observation time is too short, and the number of patients too small, to permit definite conclusions. Nevertheless, the acceptable results where the indication is correct justify a recommendation to use bovine heterografts as arterial substitutes.


Pressure-induced depolymerization of brain microtubules in vitro.

Microtubules, assembled in vitro from tubulin extracted from rabbit brain, were subjected to changes in hydrostatic pressure (200 to 10,000 pounds per square inch) and temperature (37 degrees to 0 degrees C). Increased pressure, like cooling, reversibly depolymerizes microtubules, as measured by changes in either turbidity, birefringence, or the number of microtubules seen in electron micrographs. The characteristic response of brain microtubules in vitro to pressure is similar to that of mitotic spindle microtubules in vivo.


Thrombocytopenic purpura in infectious mononucleosis-- A rare complication?

We have presented an illustrative case of thrombocytopenic purpura complicating infectious mononucleosis. Steroid therapy appeared to be beneficial although spontaneous recovery cannot be excluded. The use of the Paul-Bunnell heterophil agglutination test is recommended for patients having idiopathic thrombocytopenic purpura to rule out subclinical infectious mononucleosis. It is suggested that this syndrome be treated with the expectancy of long-term remissions. Steroids appear to be of benefit. Platelet recovery is usually complete in less than 60 days. Splenectomy should not be considered until at least two months have passed. Chronic thrombocytopenia is an unlikely complication.


Stress incontinence in the Black female.

Primary stress incontinence is probably caused by abnormality of the expulsive forces of micturition or by deficiency of the retaining forces, or both. These factors were examined and compared in Indian and Black patients, and the findings partially explain the rarity of primary stress incontinence in the latter group.


Fetal and early neonatal mortality.

A format setting out and comparing perinatal deaths is presented.  It is not new, but has not previously been used in South Africa.  Gestational age and birthweight are considered, and group predictions for mortality (and indirectly for morbidity) are made, and can be used for comparison.


The histochemical nitroblue tetrazolium reduction test in newborn infants.

Normal values for the nitroblue tetrazolium (NBT) test in full-term, premature and small-for-gestational-age infants are presented.  The NBT reduction was elevated in all groups of babies studied.  There was no statistical difference between the groups and the range was wide.  Infected babies also showed elevated NBT reduction.  However, 60% of the results obtained in the infected group fell within the same range as those obtained in normal neonates.  This renders the test unhelpful in the diagnosis of bacterial infection in the neonatal period.


Vascular access for hemodialysis by bovine graft arteriovenous fistulas.

A technique has been developed for vascular access in chronic dialysis using bovine graft arteriovenous fistulas in the forearm. Indications for use of bovine arteriovenous fistulas are failures of arteriovenous shunts and standard arteriovenous fistulas at the wrist or as a primary procedure in the event that arterial inflow or venous outflow are inadequate. Choice of either a straight or loop graft is dictated by the vascular anatomy. Loop grafts, orginating from the brachial artery, should be used for inflow problems; straight grafts, originating from an artery at the wrist, should be used for outflow problems. Results have been excellent in this series of 39 grafts in 36 patients observed from two months to one year with a follow-up average of six months. Ninety per cent of the grafts continue to function or functioned until successful transplantation or the death of the patient. Advantages of bovine graft arteriovenous fistulas compared with other fistulas include ease of access, high flows and decreased incidence of hematomas. The major complication has been thrombosis, and this incidence, most likely, can be decreased by more careful selection of the type of graft placement according to the vascular anatomy.


[Indications for prostaglandins in the field of reproduction in farm animals (author's transl)].

Parenteral administration of 2.5-5 mg. of prostaglandin F2alpha to horses, 15 mg. to heifers or 25-30 mg to lactating cows and 15 mg. to sheep will induce regression of the corpus luteum (luteolysis) and a fertile oestrus within 48-72 hours. Because of their luteolytic effect prostaglandins may be used in various indications in the field of reproduction. An exception is the pig in which administration of prostaglandins does not induce luteolysis before D12 and therefore fails to induce oestrus. In horses, cattle and sheep, administration of prostaglandins during the first four days of the cycle is ineffective. In the present paper, a few indications for the use of prostaglandins are described, including induction of oestrus (in cases of suboestrus), synchronisation of oestrus, termination of unwanted gestation, elimination of a persistent corpus luteum (purulent endometritis, pyometra, mummified foetus), induction of parturition. In addition, some other indications are listed, such as reduction of the interval between parturition and conception, chronic endometritis, hydroallantois, luteinized cysts and suboestrus post weaning. In the opinion of the present authors, the most important field for the use of prostaglandins will be that of induction and synchronisation of oestrus. As regards the fertility of synchronized oestrus induced by prostaglandins, it is stated that, in cattle and horses, this is superior to that following treatment with progestagen. Extensive field trials will be required to determine whether the fertility of oestrus induced by prostaglandins is equivalent to that following spontaneous oestrus.


Specific role of magnesium ion in protecting the anticomplementary effect of DNA in immune hemolysis.

When a constant quantity of denatured DNA required for C-fixation reaction was employed as the antigen, an anticomplementary action of DNA was frequently observed. In order to cope with this difficulty in the analysis of C-fixation, the relationship between DNA, Mg2+ and C was investigated. It was found that this phenomenon was closely related to the flexible conformation of DNA which is highly influencd by Mg2+. Further, this effect could be eliminated in the presence of 5MM MgCl2. The mechanism of the elimination by Mg2+ of the anticomplementary effect of DNA was discussed.


[Colony size spectra of 60Co-gamma-irridiated CHO fibroblasts following freeze and thaw cycles].

The production of reproductive lethal cell lesions by freeze and thaw cycles has been studied by means of colony size spectrometry in tetraploid CHO-fibroblastoma protected with glycerine. The verification sensitivity of this method is compared with that of the colony formation test, the survival curve of cells and the relative multiplicity. 20 days after a freeze and thaw cycle only  the spectrometry of the colony size and survival curve of the cells and colonies suggest a cell lesion. After 44 days, changes as a consequence of reproductive lethal lesions can be detected only in the spectrum of the colony size. Survival curves of the colonies, survival curves of the cells and relative multiplicities determined on cell strains 44 days after a freeze and thaw cycle  are not significatively different from the results of non-frozen control cells. The relation of the average cellular multiplicity after a freeze and thaw cycle to that of the nonfrozen control cells approaches the value of 1 with increased cultivation period after a freeze and thaw cycle. The reproductive lethal lesion after a freeze and thaw cycle is also decreasing with an increased cultivation period. Proliferation lesions by means of 60-Co gamma irradiation have been influenced in dependence of the dose by 20 days of freeze and thaw lesions of a cell population.


Estriol concentrations in plasma of normal, non-pregnant women.

Using a rabbit antisera directed against estriol-3-0-carboxy methyl ether complexed to BSA, an immunoassay for estriol (1) was developed. The mean plus or minus SE concentration of estriol in 18 women in days 5-7 of their cycle was 7.9 plus or minus 0.6 pg/ml which was significantly (P less than 0.01) less than the mean value of 11.1 plus or minus 0.8 pg/ml in 15 women in days 20-22 of the cycle. In 3 of 6 women in whom plasma samples were drawn frequently during their cycle, an estriol peak occurred coincident with the estradiol peak. In 3 women from whom plasma was obtained several times during the course of a day estriol levels did not appear to vary significantly. In 8 women who were on oral contraceptives the mean level of estriol was 7.6 plus or minus 1.5 pg/ml. In 8 post-menopausal women the mean level was 6.0 plus or minus 1.2 pg/ml which is significantly (P less than 0.01) less than the mean luteal phase value but not less (P greater than 0.1) than the follicular phase or oral contraceptive user values. We conclude that some of the circulating estriol is directly secreted by the ovary of normal women.


Chronic diabetes followed by chronic cerebral ischemia induced by bilateral carotid artery ligation in arteriosclerotic versus nonarteriosclerotic rats.

Male and female, arteriosclerotic (breeder) and nonarteriosclerotic (virgin), Sprague-Dawley rats were made severely diabetic with alloxan. Two weeks later experimental animals had both carotid arteries ligated to induce a state of acute cerebral ischemia. After six weeks of cerebral ischemia either with or without severe diabetes the animals were killed. Animals which survived either the acute induction of diabetes or cerebral ischemia did not manifest any new episodes of cerebral ischemia. Subjects with combined diabetes and cerebral ischemia manifested the greatest loss in body weight, adrenal hypertrophy and thymus gland involution, increased levels of serum CPK and SGOT, but decreased SGPT and LDH, hyperglycemia and hypertriglyceridemia, and the most extensive cerebral edema. It is suggested that diabetic rats may have a greater predilection toward cerebrovascular accidents because the diabetic state contributes not only to an exacerbation of atherosclerosis, but also complicates any condition of cerebrovascular ischemia by creating extracerebral edema.


Outpatient argon laser iridectomy for angle closure glaucoma: a two-year study.

A technique for iridectomy in the the treatment of angle-closure glaucoma utilizing laser beams has been developed. The operation is performed in two steps. In step 1 a partially penetrating burn of the iris is made to produce an iris hump. In step 2 a penetrating burn is used to pierce the crown of the previously produced hump. Tables 1, 2, and 3 summarize current recommendations and the detailed steps that must be followed (without exception) to achieve success with this technique. Of 22 phakic eyes, fellow eyes, or eyes with narrow-angle glaucoma, instantaneous, permanent iris perforation was produced in all except two. In these two, a second treatment on the following day produced a permanent perforation. Serious complications were encountered in only one patient who received treatment at a greater energy level than we now recommend. In that patient striate keratopathy became apparent, as well as a decrease in vision which has lasted five months. No significant complication was encountered in any eye treated with the currently recommended procedure.


Suicide survivors. A follow-up study of persons who survived jumping from the Golden Gate and San Francisco-Oakland Bay Bridges.

Interviews with seven of ten known survivors of jumps from the Golden Gate and San Francisco-Oakland Bay bridges showed a unique association between the Golden Gate Bridge and suicide. The study went beyond exploring the nature of suicidal jumps and shed new light on the experience of nearly dying. All the survivors described this experience as tranquil and peaceful. None of them experienced life events or distant memories passing through their minds or before their eyes. However, all of them experienced transcendence and spiritual rebirth phenomena. Suggestions for preventing suicides from the Golden Gate Bridge are discussed, including the construction of a suicide barrier.


The effects of lavour time on neonatal depression.

The effects of labour time on neonatal depression were investigated in 1072 cases. It was found that the everage Apgar score assessed at one minute post-parturition decreased significantly as a function of duration of labour. Additionally, the incidence of neonatal depression (Apgar indes of 7 or less) was found to increase significantly with increase significantly with increases in labour duration. Apgar indices taken five minutes after birth did not reveal any significant effects related to duration of labour. Further analysis of the labour conditions indicated that the effects of labour time on the condition of the infant was greater in spontaneius labours than induced or stimulated labours. In spotanious labours, the five-minute Apgar score continued to be influenced by duration of labour. After five minutes individual differences were clearly observable in all labours.


[Studies on the metabolism of benzo(a)pyren in alveolar-macrophages. I. Uptake of benzo(a)pyrene and induction of benzo(a)pyrene hydroxylase (author's transl)].

Alveolar macrophages play a significant role in the elimination of inhaled foreign compounds and particles from the lung. The question arises, if alveolar macrophages participate in the detoxification or activation of environmental carcinogenic compounds. In the first communication on this subject we describe experiments concerning the uptake of benzo(a)pyrene and the activity of the metobolizing enzymes. The alveolar macrophages are obtained by lung lavage from guinea pigs (Fig. 1,2,3). The cells are grown in monolayers in petri dishes or on the surface of cover slips or glass-vials. The uptake of benzo(a)pyrene in alveolar macrophages is measured by a microfluorimetric method in single cells and by using labelled substrate. The results obtained by both methods indicate that the uptake is terminated between 1-2 h (Fig. 4, 5). The kinetics of uptake and elimination (Fig. 8, 9). are influenced by the concentration of serum (Fig. 6) and benzo(a) pyrene (Fig. 7) in the medium. Two mechanism for the uptake in the alveolar macrophages are discussed: diffusion and pinocytose. The activity of the metabolizing enzymes (benzo(a)pyrene hydroxylase, aryl hydrocarbon hydroxylase)increases during incubation with benzo(a)pyrene (Fig. 10, 11) and is dependant on the concentration of benzo(a)pyrene in the growth medium (Fig. 12). The enzyme activity is inducible also by other polycyclic hydrocarbons (Tab. 1). The induction is inhibited by actinomycin D and cycloheximid (Tab. 2). The activity of the enzymes in guinea pig alveolar macrophages is comparable to the activity in leucocytes and alveolar-macrophages from humans (Tab. 3, 4).


[Conditions of development of a secondary immune response in guinea pig lymphoid cell cultures].

On addition of a specific antigen to the cell culture of the lymph nodes of the immunized guinea pigs there was seen an intensification of the synthesis of the DNA and of the antibody formation. Both processes occurred more intensively in incubation of cells on a medium with an addition of rabbit antiserum to the guinea pig erythrocytes than on a medium with a normal homologous serum. It is supposed that the optimal conditions for the initiation of antibody formation in the lymphoid cells were created in case of a combined action of a specific antigen-inductor and a nonspecific stimulant intensifying the DNA synthesis.


Acute treatment with calcitonin in primary hyperparathyroidism and severe hypercalcaemia of other origin.

Porcine or salmon calcitonin was given, as emergency treatment for 17 patients with hypercalcaemia, mostly of a severe degree. A lowering of serum calcium was achieved in all of 11 patients with primary hyperparathyroidism and in another 4 with malignancies. In most of the patients, the lowering of serum calcium level was accompanied by a pronounced clinical amelioration. This made possible successful parathyroidectomy without complications in the patients with primary hyperparathyroidism. In all patients except one, a decrease in serum creatinine was observed during treatment. Creatinine clearance was studied during calcitonin treatment in 2 patients and showed an increase. Calcitonin was ineffective in 2 of the patients with hypercalcaemia: one with plasmacell sarcoma of the lungs and another one with sarcoidosis. No serious side-effects were observed. Due to its quick action and lack of toxic effects, calcitonin is recommended when a prompt reduction of serum calcium is of vital importance.


Functional anatomy of canine cardiac nerves.

In 20 anesthetized dogs the thoracic autonomic nerves were carefully exposed in order to determine which produced cardiovascular responses when the afferent or efferent component of each was stimulated. Efferent parasympathetic and sympathetic fibers arise from the caudal cervical ganglion regions bilaterally as well as from the vagus caudally to that ganglion. The majority of negative chromotropic, dromotropic and inotropic fibers arise from the vagus or near the recurrent laryngeal nerves; however, some small parasympathetic fibers also arise from the vagi down to the level of the pulmonary vessels. Efferent sympathetic nerves are relatively large with the exception of the stellate cardiac nerves, and produce specific positive chronotropic or inotropic responses. Afferent fibers are numerous in the recurrent cardiac, innominate, ventromedial and dorsal nerves and not very numerous in both stellate cardiac nerves as well as in the nerves at the level of the pulmonary vessels; thus there are numerous cholinergic and adrenergic efferent fibers which exhibit specific chronotropic or inotropic responses. The correlation between neural anatomy and specific physiological cardiodynamics illustrates beautifully the interrelationship of structure and function which exists within the autonomic nervous system.


The postnatal histology of the epididymis in buffalo (Bubalus bubalis).

The epididymis of buffalo is differentiated into 6 regions. The head represents the first 3 regions, the body the 4th region and the tail the 5th and 6th region. At 3-30 weeks, the epithelium is simple high columnar with few basal cells in region I, simple low columnar with few basal cells in region II, pseudostratified low columnar in regions III, IV, V, and pseudostratified low columar in region VI. As age advances, the epithelium increases in height and shows a tendency toward advanced pseudostratification. The basal cells are greater in number in regions III, IV and V than in the other regions of the epididymis. The epithelial cells contain stereocilia in region I at 3 weeks and regions III, IV and V at 30 weeks, whereas they are absent in regions II and VI. The tubules in region I are the smallest in diameter while the tubules in region VI have the largest diameter.


[Cholinoreception of chick embryo myocardial explants].

The effects of acetylcholine, subecholine (selective nicotinomimetic) and methylfurmetide (selective muscarinomimetic) on the spontaneous contractions of atrial and ventricular explants from the heart of 408 day embryos as well as of mixed explants, have been studied by means of a special photoelectric device. In most of the experiments, acetylcholine reduced the rate of contractions, the sensitivity of preparations being increased with the age of embryos. Preliminary atropine treatment reversed or significantly decreased acetylcholine effect. Subecholine usually increased the contraction rhythm, whereas methylfurmetide decreased the spontaneous activity.


Spongy degeneration in the central nervous system of domestic animals. Part I: Morphology.

Spongy degeneration or status spongiosus of the central nervous system (CNS) was described in a number of domestic animal species, notably sheep, cattle, pigs and in one goat. The condition was characterized by diffuse or focal vacuolation, or polymicrocavitation of the CNS, particularly the white matter. The vacuolation showed a well defined pattern of distribution following a number of myelinated tracts in CNS white matter, in isolated fibres crossing grey matter in the brain stem, and along grey and white matter borders in the cerebrum and spinal cord. The vacuoles were not altered by a variety of methods of rapid brain fixation, processing and staining. The appearance of the vacuolation repeatedly favouring the same areas in the CNS in a large number of animals studied, its common origin either by hepatocerebral disease or hyperammonaemia, strongly suggests that CNS spongy degeneration of domestic animals is a distinct disease entity.


Spongy degeneration in the central nervous system of domestic animals. Part II: Chemical analysis and vascular permeability studies.

Two experiments were completed in which brains and spinal cords from lambs affected with spongy degeneration of the central nervous system (CNS) were analysed for water, sodium and potassium, as measures of cerebral oedema. In a third experiment, lambs with CNS spongy degeneration were tested for permeability of cerebral blood vessels by intravenous injections of Evans blue. The CNS spongy degeneration was produced by poisoning with the hepatotoxic pyrrolizidine alkaloid lasiocarpine. In the first experiment, 2 male lambs were poisoned by lasiocarpine and a third injected with saline alone. One lamb injected with lasiocarpine showed widespread spongy changes in the CNS and the other 2 showed normal brains. In the second experiment, 5 males lambs were poisoned by lasiocarpine and 5 were injected with saline. Three of the 5 poisoned lambs showed widespread spongy changes, a fourth showed minor vascuolation and the remaining 6 had normal brains...


Spongy degeneration in the central nervous system of domestic animals. Part III: Occurrence and pathogenesis  hepatocerebral disease caused by hyperammonaemia.

Severe spongy degeneration of the central nervous system (CNS) was seen in 11 cattle, 19 sheep, 4 pigs and 1 goat, associated with a variety of hepatic diseases, particularly those caused by hepatotoxic pyrrolizidine alkaloids. It was also seen in a milder form in 2 of 8 horses examined, 1 dog of 5 dogs examined, and in 1 rabbit only of a large number of laboratory animals examined. This paper reports results of experiments which confirmed initially that the CNS disease cold be caused by pyrrolizidine alkaloid intoxication. This was done by poisoning lambs with lasiocarpine. As the disease was seen in hepatoses not caused by pyrrolizidine alkaloids, the hypothesis that CNS spongy degeneration in lambs could follow any hepatic disease irrespective of its cause, was tested by poisoning lambs with allyl formate, an hepatotoxin chemically unrelated to pyrrolizidine alkaloids. Three of 4 lambs poisoned by the allyl formate showed spongy degeneration in their brains. As the CNS spongy degeneration was an apparent form of hepatocerebral disease, an experiment was conducted to show that the neural disease in sheep was caused by hyperammonaemia. CNS spongy degeneration developed in the brains of all sheep infused intravenously with ammonium acetate, and advanced spongy changes developed in the sheep infused for more than 3 days. The cerebral changes were probably temporary, since sheep infused for 5 days and retained for 3 weeks showed marked regression of vacuolation. Hyperammonaemia caused by intravenous ammonium acetate infusion is a simple, rapid model of CNS spongy degeneration. The syndrome, CNS spongy degeneration caused by hepatic failure and hyperammonaemia, is probably one of the morphologic expressions of hepatocerebral disease in domestic animals and could be an analogue of similar congenital and hepatocerebral diseases in man.


[Comparative studies of human and animal sera containin g anti-HB-8 antibodies].

In a material of 768 sera obtained from blood donors and patients and 150 sera containing HBs antigen it was investigated whether the available animal sera (horse, swine, goat) with anti-HBs antibodies meet the requirements of diagnostic sera. It was found that none of these anti-HBs animal sera was better than the human serum used as yet. Only the specificity of horse anti-HBs antibodies was equal to the human serum, hence horse serum could be used for diagnostic purposes in routine investigations by the precipitation and complement fixation method. The swine and goat sera did not ensure detection of all HBs antigens which are detected using human or horse serum.


Case report: injury of the spinal cord at birth.

Spinal cord injury may occur as a severe complication to delivery. In the vast majority of such cases the injury results from a traumatic breech delivery, but cases of injuries after cephalic presentation and fetal malposition have also been described. Two cases were reported. One of the infants died at the age of 8 months and neuropathological examination of the brain and spinal cord was performed. The other child, now 6 years old, is still alive. Incidence, mechanism of injury, clinical and morphological features, and treatment are briefly discussed.


A study of some biological and socio-economic factors in low birth weight.

Of 3841 children born alive in Malmö in Sweden in 1966, 188, 4.9% had a birth weight of larger than 2500 g. We studied these children with their families and a control in order to form an opinion on the role played by certain social and biological factors in the aetiology of LBW in a country with a relatively high average standard of living. Biological factors were analysed, such as the mother's age, parity, stature, and weight, as well as purely socio-economic factors such as the mother's civil staatus, the social group of the mother and father, income, mother's allowance in case of illness, social help or investigations regarding one or more members of the family, as well as the frequency of immigrants. The combined effect of various socio-economic factors was judged by help of a "social score". The results were analysed for 3 different groups of low birth weight, appropriate for gestational age, small for gestational age and multiple births. Judging from our investigation, biological factors probably play the greatest role in the question of LBW but these factors are difficult to distinguish from socio-economic factors which probably still play a certain role in the group preterm children, appropriate for gestational age.


Malignant hemangioendothelioma of the heart with hematological disorders.

An autposy case of a 30-year-old house wife with malignant hemangiothelioma of the heart was reported.  This case was also accompanied by marked anemia, thrombocytopenia, leukoerythremoid reaction and hypofibrinogenemia.  The spread of tumor was so wide that only the alimentary tract and the skin were free from metastases of the tumor.  Many of the metastatic foci showed marked hemopoiesis intra tumori.  A short discussion was made on the hematological abnormalities associated with vascular tumors.


Twitching motility and possession of polar fimbriae in spreading Streptococcus sanguis isolates from the human throat.

A collection of 19 strains of alpha haemolytic streptococci, isolated from throat swabs and characterized by production of spreading zones around colonies on blood agar, was found to constitute a very homogeneous group with morphological, physiological and biochemical characters corresponding to those of streptococci of ser-group H, or Streptococcus sanguis, and they all appeared to possess the group H antigen. They all had a common agglutinogen and, in addition, heterogeneous agglutinogens. The spreading growth, which appears to be a common property of S. sanguis, was due to twitching motility, and the spreading cultures possessed polar fimbriae. tneither twitching motility nor the possession of polar fimbriae have been observed in gram-positive bacteria before.


Studies on polysaccharide C of Staphylococcus epidermidis. 1. Isolation and chemical characterization.

Polysaccharide C (poly C) has been isolated from two strains of S. epidermidis and characterized chemically. The results suggest that poly C is a wall N-acetylglucosaminylglycerol teichoic acid, linked through 1:3-phosphodiester linkages. One poly C preparation contained only beta-linked N-acetyglucosamine, the other traces of alpha-linked sugar in addition. The degree of substitution of sugar in the poly C preparations from the two strains was about 50 and 25 per cent.


The oxygen tension in transudate of the middle ear.

The pO2 of transudate in the middle ear was measured in situ by a small pO2-electrode introduced through the tympanic membrane. Errors involved in some previous methods using aspiration of gas from the middle ear were avoided by the present method since contamination by air from outside of the drum was almost completely eliminated. Seventeen patients, of whom the majority had a naso-pharyngeal carcinoma or chronic otosalpingitis, were investigated. The mean pO2 of the middle ear transudate was 46 mmHg or 6.5% with a pO2 range between 10 and 108 mmHg. Investigations of the function of the Eustachian tube by the aspiration-deflation method after application of a transmyringeal tube was performed in 10 of the patients, revealing no passage through the Eustachian tube. Among these 10 patients only 4 had a passage of air on Politzer, and these had a higher pO2 in the middle ear transudate than the remaining 6 patients in whom Politzer was performed with a negative result.


Disappearance of 3h-corticosterone from the serum of obese-hyperglycemic mice (gene symbol ob).

The disappearance of 3H-corticosterone from the serum was measured in obese-hyperglycemic mice and their lean litter mates of various ages. At 1 month of age the serum half-life of the injected tracer was the same in the obese and lean animals. In the 2, 5 and 12 months old mice the tracer hormone disappeared faster in the obese mice than in their lean controls. The present results confirm that the previously observed enlargement of the adrenal cortex and the increased secretion of corticostercoids by adrenal cortexby adrenal glands in vitro in fact indicate a considerably hyperadrenocorticism in the obese mouse. Furthermore, the difference in disappearance rate of corticosteroids in vivo between obese and lean mice approximately parrallels the age variation of the other metabolic abnormalities of the syndrome suggesting that the hyperadrenocorticism is part of the multiendocrine disturbance which manifests itself as the obese-hyperglycemic syndrome.


Measurement of endometrial blood flow in guinea-pig uterus by clearance of intraluminally applied 133xenon: effects of oophorectomy, estrogen treatment and pregnancy.

Endometrial blood flow (EBF) was studied atraumatically in guinea-pigs by the 133xenon clearance technique. With the aid of an otoscope, a xdnon-saline solution was deposited via the vagina through a cannula into the uterine lumen. Radioactivity curves were obtained by a small external scintillation detector. Oophorectomy lowered total flow wheras this was markedly increased (also per unit weight) by estrogen treatment, alone or in combination with oophorectomy. During early pregnancy there was a tendency to increase in the flow, while the values (for the parietal decidua) were markedly reduced at later stages of pregnancy. In the fetus-placenta unit (133xenon solution injected intra-amniotically) the flow was three times higher than in the parietal decidua at this advanced stage of pregnancy.


Effect of Mycoplasma gallinarum on the replication in vitro of goose parvovirus strain "B".

Replication in vitro of the goose parovirus strain "B" was inhibited by Mycoplasma gallinarum co-infection. This effect could be prevented by continuous supplementation of cell cultures with arginine. The infection of cell cultures with Acholeplasma axanthum did not influence virus replication.


Drug dependence as an adaptive response: studies with ethanol in mice.

When mice were kept continuously intoxicated by inhalation of ethanol, physical dependence developed progressively, reaching its maximum in about 2 weeks. Decay of physical dependence during periods of sobriety was complete in about a day. These rapid time courses are consistent with a theoretical model in which alcohol inhibits and simultaneously stabilizes its target. This target may be located in central adrenergic synapses, because interference with function of such synapses facilitated the alcohol withdrawal reaction and because strain differences in withdrawal seizure scores correlated well with strain differences in reserpine effects.


Aminergic brain system interactions and psychopathology.

Some data from basic neuropsychopharmacological studies, behavioral pharmacological research, and clinical investigations are reviewed briefly, and the conclusion is that single-amine theories of complex behaviors or broadly defined psychopathological states are inadequate. The next generation of hypotheses relating amines to behavior must take into account the likelihood that different components of behavior are mediated by different amine systems. Further, it appears likely that many amine systems interact with one another in a regulatory fashion and that the final result-the behavior-may reflect the functions of a system of components rather than those of a particular set of aminergic neurons.


Microtubular proteins and concanavalin A receptors.

The inherent topographical distribution of Con A binding sites (CABS) is disperse or random in all cell types studied using hemocyanin to mark CABS in surface replicas. In virally transformed cells, the addition of Con A leads to the formation of clusters (CABS). A role for microtubules is suggested in this process since colchicine treatment of transformed cells and Con A addition lead to the aggregation of Con A into a "cap". During phagocytosis CABS are selectively removed from the surface. This selective movement is abolished by drugs that disrupt microtubules. Binding of Con A or RCA to intact cells at 37 degrees C leads to the removal of their receptors from the surface, presumably by "micropinocytosis".


The characteristics of succinylated con A induced growth inhibition of 3T3 cells in tissue culture.

The growth of untransformed 3T3 fibroblasts can be inhibited by dimeric, non-agglutinating concanavalin A prepared by succinylation (Suc-CON A). This growth inhibition is non-toxic, reversible, and specific for Suc-Con A binding; the cell density at which growth terminates is dependent upon the final cell number and independent of the initial (i.e., plating) density. The part of the cell cycle during which Suc-Con A can exert its growth inhibitory effect appears to be restricted to mitosis and/or early G-1 phase.


Modification of the biological activities of concanavalin A by anti-concanavalin A.

Concanavalin A (Con A) bound to cell membrane glycoproteins, may be dissociated from the membrane receptors by competitive ligands such as alpha-methyl-D-mannoside. Addition of antibody to Con A to the system forms complexes of antibody and Con A which are still bound to the membrane receptors. Such complexes are not dissociable from the membrane by alpha-methyl-D-mannoside. Presence of the complexes on the membrane is monitored by radioactive label or by passive lysis of the cells with guinea pig complement. Antibody to Con A can completely suppress Con A mediated stimulation of lymphocytes as measured by incorporation of tritiated thymidine. However production of lymphokines involved in migration inhibition, enhancement of plaque forming cells or blastogenesis are differentially suppressed by antibody to Con A.


Protective action of ascorbic acid and sulfur compounds against acetaldehyde toxicity: implications in alcoholism and smoking.

Acetaldehyde is a toxic substance common to heavy drinking of alcohol and heavy smoking of cigarettes. It has been implicated thereby in diseases of the cardiovascular, respiratory, and central nervous systems. Protection against acetaldehyde toxicity (i.e. anesthesia and lethality) was studied in rats by oral intubation of test compounds 30-45 minutes prior to oral intubation of a standardized oral LD 90 dose (18 millimoles/kilogram) of acetaldehyde. Animals were monitored for anesthesia (loss of righting reflexes) and lethality for 72 hours. A total of 18 compounds was tested. L-ascorbic acid at 2 millimoles/kilogram (mM/kg) showed moderate protection against anesthesia and marked protection against lethality. Greatest protection against anesthesia and lethality was obtained at 2 m M/kg with each of the following: L-cysteine, N-acetyl-L-cysteine, thiamin-HCl, sodium metabisulfite, and L-cysteic acid. A combination of L-ascorbic acid with L-cysteine, and thiamin-HCl at reduced dose levels (2.0, 1.0 and 0.3 mM/kg, respectively) gave virtually complete protection. A detailed literature review is presented of the rationale and significance of these findings. Our findings could point the way to a possible build-up of natural protection against the chronic body insult of acetaldehyde arising from heavy drinking of alcohol and heavy smoking of cigarettes.


Complex atrial arrhythmias studied by suction electrode technique.

Two elderly patients with coronary heart disease, chronic pulmonary disease, and complex atrial arrhythmias are presented. The suction electrode technique for right atrium monophasic action potential recording was used. This recording allows better analysis of the atrial arrhythmias and estimates the stability of focal activity.


Scanning electron microscopy of volk absorption in early chick embryos.

Fresh pullet eggs (White Leghorn Strain) were incubated from 6-19 hours. Blastoderms were fixed in situ with aldehyde fixative, post-osmicated in 2% OsO4, dehydrated in acetone, critical-point-dried, mounted ventral side up, coated with palladium-gold wire and observed in a Cambridge Stereoscan S4 scanning electron microscope. Large extracellular yolk granules had a smooth surface and appeared to break up into smaller particles. Similar particles have been observed intracellularly in transmission electron microscopy. Numerous microappendages, mostly ruffles, suggest phagocytosis as a method of absorption of yolk granules into the cells. Absorption of yolk by the cells of the blastoderm involves an initial break up of yolk granules followed by phagocytosis.


Anti-horseradish peroxidase associated with Golgi complex of antibody-forming cells.

Observations are reported on the localization of anti-horseradish peroxidase in antibody-forming cells in popliteal lymph nodes following a single injection of antigen. Reaction product, marking the site of antibody, was observed not only in the ergastoplasm and cisternae of the Golgi complex, but also in globules associated with the Golgi complex.


Eastern equine encephalomyelitis. Histopathologic and ultrastructural changes with isolation of the virus in a human case.

Enveloped Toga virus particles were demonstrated by means of an electron microscopy in the brain tissues of a 3-year-old girl with acute encephalitis. Areas of demyelinization and necrosis throughout the white matter and brainstem were revealed by light microscopy. These viral particles were identified as eastern equine encephalomyelitis virus in postmortem isolation of the virus utilizing young mice and complement-fixation studies. To the authors' knowledge, this is the first demonstration of eastern equine encephalomyelitis virus particles in human tissues by electron microscopy.


Structure of the spleen in idiopathic thrombocytopenic purpura.

The structure of the spleens of 12 patients with idiopathic thrombocytopenic purpura (ITP) who underwent splenectomy was studied. The white pulp was characterized by the presence of large numbers of lymphatic nodules containing highly reactive germinal centers. The marginal zone contained large numbers of vessels surrounded by plasma cells. These findings imply active antibody production and are consistent with the concept that the spleen is a major source of antiplatelet antibody production in ITP. Large numbers of platelets in various stages of degradation were seen in cords, particularly in the marginal zone. They appeared both extracellularly and with the cytoplasm of macrophages. It appeared that platelet destruction was initiated by focal cytoplasmic degradation and resulted in formation of cellular debris. These findings indicate that the spleen plays a fundamental role in the pathogenesis of ITP, involving synthesis of antiplatelet antibody, localization of platelets in a milieu rich in this antibody, and subsequently, phagocytosing of immune-damaged platelets.


The Middleton outbreak: 125 cases of foodborne salmonellosis resulting from cross-contaminated food items served at a picnic and a smorgasbord.

One hundred and twenty-five of 173 people who ate at a picnic and/or a smorgasbord prepared by a bar-restaurant in a Midwestern town in September 1973 developed diarrhea, abdominal cramps, and other symptoms 23 hours (median time) later. Eleven were hospitalized. Stool cultures from 18 ill individuals grew Salmonella infantis, Salmonella agona, and Salmonella schwarzengrund. Stool cultures from 5 of 8 restaurant employees grew S. infantis or S. agona. Cultures of remaining foods and food-contact surfaces were negative. Food-specific attack rates, based on interviews with 121 eaters, implicated potato salad and chicken dressing as vehicles of transmission, both likely contaminated when prepared in pans that shortly before contained uncooked, chicken pieces suspected to have harbored salmonellae. Chickens were eventually traced to 3 farms where feed samples were found to contain Salmonella typhimurium and Salmonella cubana, raising the possibility that other feed samples may have contained the serotypes responsible for the outbreak. The main control measure was temporarily closing the food service, which was to have catered a large church picnic the next day. The outbreak had an economic impact estimated at $28,733.


General models for segregation analysis.

Theoretical details are given of various oligogenic models for segregation analysis that are available as a general segregation analysis ("GENSEG") package, programmed in FORTRAN iv. The models allow for up to two autosomal loci and one X-linked locus, normally distributed or dichotomous phenotypes, variable age of onset, and various ascertainment functions (including one that allows the probability of becoming a proband to be dependent on the age of onset). Current programs are limited to the analysis of 2-generational data, using the joint likelihood of the sibship and parental phenotypes, unless it can be assumed that the pedigrees being analyzed are a random sample from the population; half-sibships and twins, however, are explicitly allowed.


Management of idiopathic thrombocytopenic purpura during pregnancy.

Management of idiopathic thrombocytopenic purpura (ITP) during pregnancy requires concern for both fetal and maternal morbidity and death.  A review of 14 pregnancies revealed significant maternal morbidity but no maternal deaths.  The perinatal mortally was21 per cent.  Current recommendations for management include: (1) corticosteroids, (2) splenectomy if response is unsatisfactory with (1), (3) liberal use of platelet transfusion if surgical intervention is required in the face of significant thrombocytopenia, and (4) careful observation of the newborn infant and treatment with corticosteroids and/or platelets if thrombacytopenia is severe.


Hysteroscopy: a useful diagnostic adjunct in gynecology.

Advancements in instrumentation and the introduction of new media for uterine distention have enhanced the potential of hysteroscopy as a diagnostic technique.  In a10 month period at the University of Minnesota, hysteroscopy was preformed in 110 patients with suspected urine pathology.  Paracervical block ansthesia was used in 70 ambulatory patients and the remainder were investigated under general anesthesia because ofconcomitant laparoscopy or planned surgical intervention.  Both dextran 30 per cent and5 per cent dextrose in water were used for uterine distention.  Hysteroscopic abnormalities were found in 70 per cent of the patients ezamined.  These findings included endometrial polyps (32 patients), 12 intrauterine foreign bodies, submucous myomas (10 patients),developmental anomalies and cesarean section scar defects (7 patients), and 16 patients with miscellaneous pathologic conditions, including one patient with adenocarcinoma of theendometrium.  In 33 patients the hysteroscopic findings were normal.  In severalpatients intrauterine devices were removed under hysteroscopic control.  There were no complications related directly to hysteroscopic abservation.


Current status of artificial insemination with donor semen.

As male infertility secondary to oligospermia and azoospermia reamins refractory to treatment, donor insemination has gained greater acceptance.  Wives of azoospermic and severely oligospermic men were evaluated for donor insemination.  One hundred and thirty-four patients were found to be ovulating normally and to be free from pelvic pathology.Sixty-five accepted donor insemination.  Fifty-one conceptions accurred in 41 patients, resulting in 43 live births and 8 miscarriages.  The mean number of inseminations was 4.2 (range 1 to 13).  Eighty-three patients were found to have endocrinopathies or pelvic pathology interfering with fertility; 58 were considered candidates for corrective  therapy to be followed by donor insemination.  Conception rates approached those observed in the average population; however, there was a greater incidence of abortion and ectopic gestation.  Careful consideration of the patient prior to donor inseminationensures greater success and avoids unnecessary procedures when the patient is not considered a candidate for corrective therapy.


Changes in the transfer of nutrients across the placenta during normal gestation in the rat.

Transfer of labeled glucose and alpha-amino isobutyric acid from the maternal circulation into the fetus was studied in the rat at various times during gestation and the results were correlated with placental and fetal growth. It was found that the rate of transfer of both substances per gram of placental tissue increase markedly near term in coincidence with a simultaneous fetal growth spurt. The data suggest a bimodal sequence of growth of the conceptus with a first phase of rapid placental growth and reduced placental transfer and a second phase of slow placental growth, increased transfer, and rapid fetal growth.


Variations in the level of uterine norepinephrine during pregnancy in the guinea pig.

The uterine smooth musculature is innervated by short adrenergic neurons which are unique in that their transmitter content varies during pregnancy and under the influence of exogenous sex hormones. Uterine norepinephrine was measured fluorometrically at 25 stages throughout pregnancy in the guinea pig, which was chosen because one of the pregnant uterine horns often is devoid of fetuses and hence not subject to mechanical tension. During the initial 10 days of pregnancy, the total organ content of norepinephrine was almost doubled whether the horn contained conceptuses or not. In the horn with conceptuses, norepinephrine was subsequently reduced in the course of the remaining gestation time to reach near-zero levels at term (about 65 days post coitus). In the empty horn, the amine level was constantly elevated until the last two weeks, during which it fell to the same low values as in the contralateral horn. Cervical norepinephrine exhibited the same variations during pregnancy as the empty horn. It is suggested that the characteristic variations in uterine norepinephrine reflect a hormonal influence on the system of short adrenergic neurons, with the addition of mechanical factors in that horn containing fetuses.