Further studies on the control of ACh sensitivity by muscle activity in the rat.

1. Denervated rat soleus muscles were stimulated directly through chronically implanted electrodes and the influence of different amounts and patterns of stimuli on the acetylcholine (ACh) sensitivity of the muscle was studied. The number of stimuli was varied by giving similar trains of stimuli (10 Hz for 10 sec) at different intervals (0 to 12 hr). The pattern of stimulation was varied by giving different trains of stimuli (100 Hz for 1 sec, 10 Hz for 10 sec and 1 Hz continuously) as the same average frequency of stimulation (1 Hz). 2. Stimulation usually started 5 days after the denervation when ACh hypersensitivity was fully developed. Most stimulation procedures reduced extrajunctional ACh sensitivity to normal or below normal values within 5-21 days, and these levels were maintained on prolonged stimulation. 3. The rate at which ACh hypersensitivity disappeared increased with increasing amount and frequency of stimulation. However, as few as 100 stimuli given every 5-5 hr for 3 weeks caused a tenfold reduction of sensitivity. 4. The stimulation had little or no effect on the ACh sensitivity at the end plate. Along the rest of the fibre the sensitivity was reduced at approximately the same rate except near the tendons where it appeared to fall more slowly in some fibres. 5. The stimulation restored the resting membrane potential of the denervated fibres to normal.


Contrast constancy: deblurring in human vision by spatial frequency channels.

The perception of contrast was measured in humans by a technique of subjective contrast-matching, and was compared with contrast sensitivity as defined by threshold measures. 2. Contrast-matching between different spatial frequencies was performed correctly (especially at frequencies above 5 c/deg) despite the attenuation by optical and neural factors which cause large differences in contrast thresholds. 3. Contrast-matching between single lines of different widths was also veridical, and was not limited by the spatial integration (Ricco's Law) present at threshold. Adaptation to gratings altered the appearance of lines, and this could be best understood in Fourier terms. 4. The generality of these results was shown by matching the contrast of pictures which had been filtered so that each contained a one octave band of spatial frequencies. 5. Within the limits imposed by threshold and resolution, contrast-matching was largely independent of luminance and position on the retina. 6. Six out of eleven astigmatic observers showed considerable suprathreshold compensation for their orientation-specific neural deficit in contrast sensitivity. 7. These results define a new property of vision: contrast constancy. It is argued that spatial frequency channels in the visual cortex are organized to compensate for earlier attenuation. This achieves a dramatic 'deblurring' of the image, and optimizes the clarity of vision.


Sensitive osmometer function of juxtaglomerular cells in vitro.

The rate of renin release from viable juxtaglomerular cells was studied during prolonged superfusion of isolated rat renal glomeruli with Ringer solutions of differing osmolarities. 2. Reduction in osmolarity from 305 to 285 m-osmole/l. by lowering sucrose concentration caused renin release rate to double. A rise in osmolarity of 30 m-osmole/l. by raising sucrose concentration halved release rate. 3. The response to osmolarity was graded. During the first 30 min following a 20 m-osmole/l. decrease in osmolarity, 1-57 +/- 0-22% (S.E. of mean) of cellular renin content was released; three times this amount was released with a decrease of 50 m-osmole/l. The effect persisted at lower release rates for 60-90 min. 4. The juxtaglomerular cells were four to five times more sensitive to changes in osmolarity through sucrose than sodium chloride concentration. Changes in potassium chloride concentration (7-57 mM) had little effect. 5. Sodium chloride had no direct ionic effect on renin release outside its osmotic properties. 6. The findings support a previous proposal that the rate of renin release in vitro relates directly to the volume of the juxtaglomerular cell. The hypothesis is developed that a similar mechanism may underlie renin secretion in vivo.


Effects of fasting and semistarvation on the kinetics of active and passive sugar absorption across the small intestine in vivo.

The effects of dietary restriction on the kinetics of absorption in vivo of glucose, galactose and alpha-methyl glucoside were assessed by electrical and chemical methods in the rat jejunum. 2. The 'apparent Km', maximum absorption or Vmax (mu-mole/10 cm. 15 min) and maximum potential difference (p.d.max) were obtained for the jejunal electrogenic active transfer mechanism from the transfer p.d.s and the chemical absorption data corrected for diffusion using various graphical kinetic plots. 3. Fasting for 3 days greatly decreased the 'apparent Kms', obtained from electrical or chemical data, for all the sugars but had no effect on those for L-valine or L-methionine. Semistarvation caused a less pronounced reduction of the 'apparent Kms' for the sugars. The dietary-induced change in 'apparent Km' for glucose was also observed in the fasted hamster. One interpretation of these changes is that the affinity of the carriers for sugars increases during dietary restriction; the greater the level of restriction the greater the increase. 4. Fasting and semistarvation caused large reductions in the Vmax. These reductions were correlated with a reduced enterocyte population estimated by changes in enterocyte column size. 5. The reduction in the Vmax for galactose was mainly accounted for by the decrease in enterocyte population. In the case of glucose, other factors such as reduced enterocyte metabolism or changes in the carriers must be involved to explain the discrepancy between the large decrease in Vmax and the enterocyte column size. 6. Fasting and semi-starvation had complex, differential actions on the p.d.max for glucose, galactose and alpha-methyl glucoside. These changes did not correlate with those observed in the Vmax measured chemically. 7. A standard diet obtained from two commercial sources was found to differ greatly in its effect on the electrogenic transfer system for alpha-methyl glucoside but had no effect on those for galactose and glucose.


Voltage-clamp analysis of transmembrane ionic currents in guinea-pig myometrium: evidence for an initial potassium activation triggered by calcium influx.

Voltage-clamp analysis of ionic transmembrane currents in very small strands of guinea-pig myometrium was carried out with a double sucrose-gap technique. It was found that the electrical activity, consisting of a spike followed by a long plateau, is controlled by, at least, four ionic conductances. (1) A fast inward current is responsible for the spike generation. Its low equilibrium potential accounts, partly, for the low amplitude of the spike. (2) The fast inward current is antagonized by an early outward current which occurs almost simultaneously. This fast outward current is blocked by TEA. Its reversal potential is about -95 mV. A tenfold increase in the external K-concentration shifts the reversal potential by 50 mV. Thus, it is concluded that the initial outward current is carried by K+. (3) A slow current, whose reversal potential ranges from -40 to -10 mV, is responsible for the negative after-potential. Cl-depletion (to one-ninth) does not modify this current while Na-depletion (to one-ninth) decreases its reversal potential by about 20 mV. (4) A late current which shows delayed rectification is elicited by long pulses. Its analysis is made difficult by the change mainly of the K-equilibrium potential suggesting accumulation of K+ outside the cell membrane. (5) The availability of the inward current and of the slow current, determined in TEA solution, shows that both currents are half-inactivated by a 8 mV conditioning depolarization. Using a slope factor of -2-5 or -3 the availability curve fits the experimental values. In normal solution, the availability curve of the initial current appears complex in the hyperpolarization range. The fast outward current, which is partly inactivated at the resting potential, is restored by conditioning hyperpolarization and then antagonizes the Ca inward current more. (6) It is concluded that the fast K-current controls the spike generation and accounts for the fast repolarization of the spike. The fast and transient increase in K-conductance may be the result of a momentary local increase in Ca concentration at the internal surface of the membrane.


Interactions of rod and cone signals in the mudpuppy retina.

Interactions between rod and cone signals in mudpuppy retinal neurones were investigated by intracellular recording. 2. The mudpuppy retina contains one kind of rod (lambda max = 525 nm) and one kind of cone (lambda max = 572 nm). The responses of receptors can be distinguished on the basis of their spectral sensitivities. 3. Rod and cone responses have different time courses of recovery and absolute sensitivities. Differences between receptor responses can be used to describe inputs to interneurones. 4. There are two spectral classes of horizontal cells: L-type and C-type. L-type cells are hyperpolarized by rods and cones in varying proportion, with some cells receiving little rod input. C-type cells are hyperpolarized by rods and depolarized by cones. 5. Bipolar cell receptive field centres receive input from cones or from rods and cones. There is no correlation between the spectral properties of centre responses and their polarity. 6. Antagonistic surrounds of bipolar cells show cone or rod and cone sensitivity. They are believed to be generated by the L-type horizontal cells. 7. Some bipolar cells exhibit chromatic interactions between cone signals in the centre and rod signals in the surround, which resemble those observed between the signals of different spectral classes of cones in species known to possess colour discrimination. 8. Amacrine and on-off ganglion cells have L-type responses showing both rod and cone sensitivity. 9. It is proposed that interactions between rod and cone signals observed in mudpuppy also exist in primate retina and are at least partially responsible for certain psychophysical observations of rod-cone interactions.


Loss of alpha-bungarotoxin from junctional and extrajunctional acetylcholine receptors in rat diaphragm muscle in vivo and in organ culture.

Acetylcholine (ACh) receptors in rat diaphragm muscle were blocked by intrathoracic injection of alpha-bungarotoxin (alpha-BuTx) or [125I]alpha-bungarotoxin ([125I]alpha-BuTx). The stability in vivo of the toxin-receptor complex formed by receptors in normal muscles and receptors in extrajunctional regions of denervated muscles was compared. Toxin was lost from junctional regions of normal muscles with a half-time of approximately 6 days. The loss of toxin was accompanied by a corresponding increase in the number of free toxin-binding sites. In contrast, 65% of the toxin bound to extrajunctional regions of denervated muscle was lost in 24 hr. 2. In a second series of experiments, animals were injected with [125I]alpha-BuTx and the muscle subsequently cultured for 24 hr. Loss of toxin again occurred more rapidly from extrajunctional receptors than from junctional receptors. The loss from extrajunctional receptors was described by a single first-order rate constant whose corresponding half-time was 8-11 hr. Loss was almost completely blocked by sodium cyanide and dinitrophenol and was inhibited by puromycin and cycloheximide. The radioactivity recovered in the medium was largely monoiodotyrosine. These results are consistent with the hypothesis that toxin loss reflects intracellular degradation of toxin-receptor complex. 3. Neonatal rats were injected with [125I]alpha-BuTx and the diaphragms cultured. Radioactive toxin was lost rapidly from extrajunctional regions of muscle and more slowly from regions containing end-plates. 4. These results could be explained by a difference in turnover rates for junctional and extrajunctional receptors.


The stages of osmotic haemolysis.

The haemolysis of individual human erythrocytes has been observed using an inverted microscope and cine-camera. 2. With each permeant (glycerol, propylene glycol, ethylene glycol, urea and water) haemolysis is a multistage process. The stages are swelling, popping, reduction in volume possibly accompanied by ion leakage and, finally, haemoglobin leakage. 3. The classical haemolysis time (Th) is made up of a swelling time (Tsw) and a stress time (Tst). Tst is not negligible and with the faster permeants it may occupy more than 75% of the haemolysis time. 4. The stress time can also be divided into two parts: a K+ leak time (TK) during which the cell shrinks and a time (THb) during which haemoglobin is leaving the cell. THb occupies a substantial part of Th, from 25 to 65%, and is relatively longer in fast haemolysis. 5. There is a wide spread in the permeability coefficient to glycerol in a population of erythrocytes. The distribution is compatible with a Gaussian distribution. The mean permeability is 1-79 X 10(-6) cm/sec and the S.D. is +/0 0-45 X 10(-6) cm/sec. 6. The correlation between haemolysis time and swelling time for individual erythrocytes is poor, especially for fast haemolysis. Consequently, a measure of the distribution of haemolysis time does not give a related distribution of the swelling time or of the calculated permeability for individual erythrocytes.


Lipid A fever in cats.

In unanaesthetized cats the effect of lipid A on rectal temperature and on prostaglandin E2 (PGE2) activity in cisternal cerebrospinal fluid (c.s.f.) was examined. Lipid A was injected either intravenously or into the cerebral ventricles. 2. Lipid A injected intravenously in a dose of 1--4 mug/kg produced longlasting fever which was more often biphasic than monophasic. With a second injection a much shorter but usually hither monophasic response was produced. The cat was then for a time insensitive to I.V. lipid A but when the injections were repeated at 24 hr intervals brisk monophasic fevers were again produced. The threshold dose of I.V. lipid A lay between 0-1 and 0-3 mug/kg. 3. Lipid A injected into the cerebral ventricles in a dose of 100 ng or 1 mug produced long-lasting monophasic fever. No tolerance developed; the same or only slightly diminished responses occurred on repeated injections. The threshold dose was between 5 and 20 ng. 4. A cat rendered insensitive to I.V. lipid A gave its normal fever response to injection of lipid A into the cerebral ventricles. 5. The fever produced by lipid A injected I.V. or into the cerebral ventricles was associated with the appearance of, or a rise in PGE2 activity in c.s.f. 6. Both the fever and the PGE2 activity in c.s.f. produced by lipid A injected intravenously or into the cerebral ventricles were brought down and prevented by I.P. injections of aspirin, paracetamol, or indomethacin.


Influence of the insulin sensitive central nervous system glucoregulator receptor on hepatic glucose metabolism.

Excitation of the insulin sensitive glucoregulator receptor in the central nervous system (C.N.S.) causes an immediate decrease in the systemic blood sugar level in rats. 2. A study was made in animals that were subjected either to evisceration or to evisceration and functional-hepatectomy, in order to assess the role of the liver and pancreatic hormones in the blood sugar decrease following insulin injection into the carotid artery. 3. The results indicate that the change in the systemic blood sugar level, induced by exposing the C.N.S. to insulin, was effected through a direct influence of the receptor centre on glucose metabolism of the liver. 4. Excitation of the insulin-sensitive receptor in the C.N.S. regulates carbohydrate metabolism of the liver, both by inhibiting hepatic glucose output and by facilitating hepatic glucose uptake. 5. The data derived from these animal models reveal that the mode of transmission of the impulse from the C.N.S. region is through efferent neural pathways that directly influence the hepatic carbocydrate metabolism, and not through a modification of pancreatic hormone secretion.


Cardiovascular and endocrine responses to feeding in the young calf.

A number of cardiovascular and endocrine responses which occur during and after feeding in the unweaned calf are described. 2. There was a substantial increase in both heart rate and mean aortic blood pressure during feeding in these animals. This occurred within the first few seconds and persisted throughout the period of ingestion. 3. The concentrations of glucose, insulin and gastrin in arterial plasma rose abruptly during, or immediately after, feeding and elevated values persisted for at least 2 hr. A transient increase in glucagon concentration was also observed. In contrast, feeding appeared to produce no immediate rise in enteroglucagon concentration. 4. The adrenal output of glucocorticoids rose transiently in response to feeding but that of catecholamines was unaffected. 5. Cardiovascular responses to feeding were also examined in other species. In unweaned kids the changes were essentially similar to those observed in the calf but were less pronounced. In lambs a persistent hypertension occurred which was associated with a brief initial tachycardia. In adult dogs ingestion of solid food also caused tachycardia but although the aortic blood pressure rose for a short period at the beginning of feeding, hypotension developed thereafter. 6. The possibility that both the cardiovascular and endocrine responses, which occur during or immediately after feeding, are mediated by the autonomic nervous system is discussed.


The release of pancreatic glucagon and inhibition of insulin in response to stimulation of the sympathetic innervation.

The changes in the concentration of glucagon and insulin in arterial plasma which occur in response to splanchnic nerve stimulation have been investigated in adrenalectomized dogs, cats and sheep. 2. In dogs, stimulation of both splanchnic nerves at a low frequency (2-0 c/s) for 10 min produced a small but statistically significant increase in plasma glucagon concentration and appeared to inhibit the release of insulin. Stimulation at a higher frequency (10-0 c/s) produced a much greater increase in plasma glucagon concentration, which was normally accompanied by a rise in plasma glucose concentration. 3. Qualitatively similar changes in plasma glucagon and insulin concentration were observed in both sheep and cats in response to adrenergic stimulation. 4. Intramesenteric infusions of glucagon at a dose of 5-0 ng kg-1 min-1 in dogs produced a comparable rise in plasma glucagon concentration to that elicited by splanchnic nerve stimulation at high frequency (10-0 c/s) and invariably caused a rise in plasma glucose concentration. 5. In dogs given exogenous glucose, release of glucagon in response to splanchnic nerve stimulation was unaffected by induced hyperglycaemia. Secretion of insulin was partially inhibited by stimulation at 2-0 c/s and completely suppressed at higher frequency (10-0c/s). 6. It is concluded that stimulation of the sympathetic innervation to the pancreatic islets, at frequencies within thephysiological range, stimulates the release of glucagon and inhibits that of insulin in each of these species.


Two phases of chorda-lingual induced vasodilatation in the cat's submandibular gland during prolonged perfusion with Locke solution.

The effect of stimulation of the chorda-lingual nerve on the venous flow has been studied in cat submandibular glands perfused with Locke solution for 2-4 hr. When trains of pulses at 25 Hz were given for 1-5 sec, two distinct phases of vasodilatation were observed: a rapid initial phase of high amplitude and a slower developing more prolonged phase of smaller amplitude. Repeated stimulations did not lead to a reduction of the vasodilatory response. A close relationship was found between the duration and magnitude of the second phase of vasodilatation and the duration and magnitude of the post-stimulatory, active reuptake of potassium. When the active reuptake of potassium was prevented either by ouabain (which inhibits active transport) or by atropine (which abolishes the stimulation induced loss of potassium) the second phase of vasodilatation was severely reduced, while the initial phase remained virtually normal. It is concluded that the initial phase of vasodilatation probably is mediated by vasodilator nerve fibres. The second phase is perhaps causally related to the post-stimulatory, active transport of cations. An involvement of bradykinin formation is highly unlikely under the given experimental conditions.


Post-natal developmental changes in the length-tension relationship of cat papillary muscles.

The length-tension relationship and the effect of paired electrical stimulation were studied in right ventricular papillary muscles obtained from cats. The animals were divided into three age groups: neonatal kittens, less than 24 hr of age; infant kittens, 16--18 days of age; and adult cats. 2. The muscles were electrically driven to contract isometrically using field stimulation at 10--20% above the threshold valus. 3. At Lmax the neonatal preparations produced significantly less developed (active) tension than did the adult preparations. The resting tension at Lmax was significantly greater in the neonatal preparations than in the adult ones. The infant group occupied an intermediate position between the two other groups. 4. The response to paired electrical stimulation was less in the neonatal group than in either the infants or the adults. 5. It is concluded that post-natal developmental changes occur in the contractile properties of the myocardium of the cat.


[Mauration of unitary responses to tonal stimulation in the cochlear nerve of the kitten].

The maturation of single auditory nerve fiber responses to long-duration (500 ms) tone-bursts was studied in kittens at various stages after birth. Spike discharges were examined as a function of three criteria. 10 Latency. Mean value of the "on" peak latency was about 25 ms at 1 to 3 days after birth. It then regressed, reaching 8 to 12 ms at the end of the first week, and 2 to 4 ms at 20 days. 20 Peristimulus histograms (PSTH). Evolution of PSTH revealed the characteristic sequence of unit reactivity to long duration stimuli (i.e. on, rhythmic, and continuous responses). Rhythmic responses is assumed up to now to be related to the immaturity of synaptic junctions below the hair cells. 30 interval histograms. The interspike interval histograms of the discharges showed a similar evolution. A bimodal distribution corresponding to the rhythmic mode of reactivity, appeared at the end of the first week.


[Influence of eating modalities on water intake in dog (author's transl)].

Food and water intake of a dog which had free access to water were studied in three experimental circumstances: 1) Food given ad libitum. 2) Food given at fixed hours. 3) Food deprivation for four days followed by resumption of food intake. A) The results indicate the water intake follows a pattern, the profile, range and duration of which can be modified within 24 hrs. In spite of modifications related to food intake, a typical profile remains which suggests that water is taken according to a program which is at least partly indepdent of food intake. B) Under experimental condition 1, food and water intake were weakly related, probably revealing an acquired relationship between the meal weight and the water intake which immediately precedes and follows food intake. The correlation was strengthened when the dog was forced to eat only once a day (observation 2). On the contrary, after a period of starvation (observation 3) the previous relationship between meal weight and water intake lessens and others appear which suggest the action of direct mechanisms of shortage compensation as far as water and food are concerned.


[Intrarenal distribution of calcium and magnesium in the dog. Effect of an osmotic diuresis (author's transl)].

1 The determination of Na, Ca, Mg, and K concentrations was performed in four different regions of the dog kidney (cortex, outer medulla, inner medulla, and papilla) during antidiuresis and during an osmotic diuresis. 2 The results show a medullary concentration gradient for calcium. This gradient is much higher than that found for sodium. 3 An inverse concentration gradient from cortex to inner medulla for Mg and K is found. 4 An osmotic diuresis (hypertonic mannitol) decreases the corticomedullary gradient of Na, but does not alter significantly the intrarenal distribution of Ca, Mg and K. 5 These results consistent with an intracellular localization of Mg and K in the renal tissue. It is suggested that the medullary concentration gradient for Ca may be due either to a countercurrent multiplier system similar to that for Na, or to a higher tissular fixation of Ca in the inner medulla and papilla than in the outer medulla and cortex.


[Electroencephalographic study of the eel (author's transl)].

1 This paper describes a method for electroencephalographic recording from unanesthetized and unraistrained european eels (Anguilla anguilla L.). 2 EEG's records from the cerebellum, tectum opticum, telencephalon and olfactory bulb of the eel are compared with other fish previously studied by other authors. 3 Averaged evoked visual potentials from the telencephalon, tectum opticum and cerebellum are presented. 4 This study provides a reference point for future research on fish vigilance depth and EEG changes associated with modified environmental factors.


[Vascular responses to tilting in paraplegic subject compared to normal (author's transl)].

1 Vascular tone is higher in paraplegics than in normals, both in capacitance and resistance vessels. This is possibly correlated with the increase in circulating catecholamines which has recently been reported. 2 Tilting at 30 degrees from horizontal induces a hydrostatic increase in transmural pressure in the affected vascular bed. This pressure change causes:  an initial decrease in resistance, followed by a progressive increase which can be explained by the Bayliss reflex. The time sequence and amplitude of the responses are comparable for normal and paraplegic subjects; an increase in vascular tone of the capacitance vessels (increase in venous pressure, decrease in local blood volume). This response was constantly observed in paraplegic subjects and was absent or weak in normal subjects. 3 In conclusion, reflex changes in vascular tone due to upright posture persist after traumatic section of the spinal chord. Orthostatic hypotension and blood pooling in the lower limbs in paraplegic subjects is probably due primarly to a deficit of the pumping action of the leg muscles.


[Topography of stimulation sites with aversive effects in the rat's medial hypothalamus (author's transl)].

The intensity of the aversive effects induced by an electrical stimulation of various sites in the rat's medial hypothalamus was evaluated through analysing the relation between stimulation intensity and the induced switch-off responses. Series of "hot points" were found in both the ventro-medial and the dorso-medial nuclei. Stimulation sites with less marked aversive effects were found in a periventricular region.


[Effect of cortisol on the cellular proliferation and maturation in the cerebrum and the cerebellum of the rat: Importance of the age of the animals at the beginning of treatment].

Young rats were given either a single subcutaneous injection (1 mg at 0, 1, 4 or 8 days), or four consecutive daily injections (0.2 mg/day between 0 and 3 days; 0.4 mg/day between 4 and 7 days; 0.6 mg/day between 8 and 11 days) of cortisol acetate in order to test the influence of age on the action of corticosteroids on the biochemical maturation of the cerebrum and cerebellum in terms of their DNA, RNA, and protein contents. The results showed that: 1 The diminution of the DNA content at 35 days was greater in the cerebellum (- 16 to - 32%) than in the cerebrum (- 9 to 20%); the DNA content of the cerebrum was more affected by treatment at birth, whereas that of the cerebellum was more affected by the delayed treatments. Results were different when expressed in terms of reduction of the normal increase: the gain of DNA decreased more in the cerebrum (-70%) than in the cerebellum (-40%); but the most delayed treatment induced a greater effect in both organs. These abnormalities were not always accompanied by a significant decrease of the body weight. 2 Generally, the treatments led to an increase of the mean cell territory, expressed either in terms of decrease of the DNA concentration, or in terms of increase of the organ weight/DNA ratio. Moreover, the increase of the RNA/DNA and the protein/DNA ratios constituted an indication of an accelerated cellular maturation.


[Pulmonary stretch receptors activity during thermal polypnea (author's transl)].

1 We have studied the unit activity of 88 pulmonary stretch receptors (RPI) in the vagus nerve of the cat by using the single fibre technique. 2 In spite of a 38% decrease in tidal volume, the discharge frequency of RPI is statistically unchanged during polypnea, However, RPI are recruited earlier, but their discharge overlaps expiration. 3 Individual influences of tidal volume, temperature, and FACO2 on RPI activities are tested. During polypnea, the excitatory influences of hyperthermia and hypocapnia act against the depressing action of tidal volume reduction: RPI are still active. 4 During polypnea, respiratory rhythm and tidal volume are unchanged after bivagotomy. RPI activity seems functionally insignificant. This result suggests that the thermally induced respiratory response is mediated by structures in the upper brain stem (probably the preoptic anterior hypothalamus) and is not dependent on the integrity of the vagus nerve.


[A method for real time separation of multiple unit action potentials from intact nerves (author's transl)].

1 A method is described for on line separation and classification of individual action potentials from multi unit extracellular recordings from intact nerves.  2 this method is based on the simultaneous determination of several of the features of each action potential, especially their form and velocity. 3 provided that only a few conditions are fulfilled, each of the action potentials can be recognized, and the recognition work is achieved at the time of the generation of the action potentials. 4 The prerequisite conditions are the following: the nerve diameter should not exceed a few tenths of a millimeter. The nervous filament must be carefully dissected from the surrounding tissue. The overall frequency of the action potentials should not exceed 1000 spikes/sec.


[A comparison of the behavioral response of the field mouse (Apodemus sylvaticus L.) to a 24 hour fast as measured by actograph or in a cage].

1. The "general activity" of Apodemus Sylvaticus L. has been recorded and analysed using two techniques: a) in an actograph, several components of the "general activity" have been recorded and quantified over 24 hours, including wheel running, locomotion in various areas of the enclosure, nest occupancy, drinking, eating and hoarding; b) in a breeding cage, ten times smaller than the actograph and where the possibilities of locomotion are considerably reduced, the wheel running only has been recorded. In these two situations, we have compared the effects of a food deprivation for 24 hours. 2. In the actograph, starvation increases the general locomotion in the enclosure without detectable changes in wheel running. On the other hand, in the breeding cage, wheel running is somewhat increased. 3. Refeeding results in decreased wheel running under both experimental conditions, and restores general locomotion in the actograph to the predeprivation level. 4. These results are discussed in view of the current literature. The apparent disagreement between our results and those of other workers is attributed to the fact that the latter used experimental conditions where the measured response was predetermined by the lack of choice in expressed responses which were offered to the animal. Consequently, we suggest that the interpretation of such experiments can be improved by allowing a choice of possible behavioural response and that each of them should be recorded separately.


[Comparison of the effects of anosmia induced by either peripheral lesion or bulbectomy upon the feeding pattern of the rat (author's transl)].

In order to support the contention that the feeding pattern seen after olfactory bulb removal is due to a sensory loss, the feeding pattern of rats was studied after a peripheral chemical lesion of the olfactory mucosa. A conditioned smell aversion procedure was used to assess the occurence and duration of anosmia after the topical application of zinc sulfate to the olfactory mucosa. It was found that the sensory deficit induced by the peripheral lesion lasted from four to six days. The occurrence of the disrupted feeding pattern in the peripherally lesioned rats coincided in time with the short period of anosmia. Thus, the disruption of the feeding pattern after bulbectomy and after lesions of the central olfactory pathways is clearly the result of anosmia and not of the loss of other non-sensory functions of the olfactory bulbs.


[Level of oxytocin release induced by vaginal dilatation (Ferguson reflex) and vagal stimulation (vago-pituitary reflex) in lactating rats (author's transl)].

1. Vaginal dilatation for 30 seconds caused a rapid and brief increase in intramammary pressure which was equivalent to that evoked by 160 muU of oxytocin (Syntocinon) injected intravenously. 2. The rise in mammary pressure induced by the stimulation of the central end of a severed vagus nerve for 30 seconds (5 V, 0,5 ms, 50 HZ) was similar to the response obtained with an intravenous injection of 360 muU of oxytocin. 3. The vago-pituitary reflex leads to the liberation of large amounts of antidiuretic hormone which does not interfere with the effect of oxytocin on the mammary gland, since dexamethasone phosphate prevented the vasopressor effect without significantly affecting the increase in intramammary pressure.


[Muscular blood flow in human highlanders and in lowlanders living at altitude (3 800 m) (author's transl)].

Muscular blood flow (MBF) was measured in the tibialis anteiror muscle by the 133Xe washout technique. Measurements were made in lowlanders at sea level, in native highlanders at 3 800 m and in lowlanders who had been living at this altitude for less than 6 months. At rest and during exercise, MBF is smaller in highlanders and in the high altitude visitors than in lowlanders. If, instead of total blood flow, the red cell flow is calculated (by multiplying MBF by the haematocrit) these differences are no longer significant at rest and are minimized during exercice. These results are consistent with reduction of cardiac output and blood supply to other regions in subjects who are acclimatized to altitude.


[Total cardiopulmonary bypass in rabbits. Techniques and the effect of pulsatile perfusion pressure on hemodynamic parameters].

Fifty-two total cardiopulmonary bypasses (CA) have been performed in rabbits in order to obtain a stable preparation. The present paper deals with techniques and haemodynamic results. 1. Two kinds of priming solution have been used. Best results were obtained by using Ringer-lactate-gelatin (65 ml) and T.H.A.M. (5 ml). 2. Pulsatile arterial perfusion was performed either at uniform frequency (series A:10 experiments) or in accordance with the arterial mechanical resonance frequency of each animal (series B: experiments). The later setting resulted in better levels of maximal arterial pressure throughout the experiments (p less than 0,001). 3. The perfusion pressure flows (integrated at minute intervals), and total peripheral resistances, were studied on two groups of 4 animals each, A' and B' forming a part of A and B respectively. The flows were higher in B' after 5 min of CA (p less than 0,001), and after 40 min of CA (p less than 0,025); the flow increased during the experiment in group A' but remained in a steady state in group B'. The differences in total peripheral resistances were not statistically significant after 5 min of CA, but were smaller in A' after 40 min of CA (p less than or equal to 0,025); the difference in the variation of total peripheral resistances was statistically significant (p less than 0,025).


Eliminating self-defeating behaviors and change in locus of control.

This study investigated changes in locus of control occurring among participants in a workshop designed to eliminate self-defeating behaviors. Experimental (n = 18) and control (n = 18) groups were composed of male and female university students. An analysis of covariance indicated that the treatment group moved significantly more than the control group (p less than .001) on the Rotter I-E Scale, and movement was in the anticipated direction, toward greater internal control. The increased internal control was maintained in a follow-up administration of the I-E Scale four months later. It was concluded that the workshop brought relatively stable changes toward greater perceived internal control. Implications were discussed.


Sex differences in the comprehension of spatial orientation.

This research examined effects of instruction upon acquisition of Piaget's concept of horizontality and determined sex differences related to this acquisition. Hypotheses tested were that there are no significant differences (a) in performance on perception and prediction tasks, (b) by sex in the ability to comprehend horizontality, (c) by sex in the stage of development after instruction, and (d) by sex after instruction on the number of correct responses on horizontal tasks. Subjects were 18 male and 17 female rural, public school pupils ranging in age from 8 years, 0 months to 9 years, 11 months. Test instruments were a cylindrical bottle half-filled with colored water and eight pictures of bottles positioned at angles from 0 to 315 degrees at increments of 45 degrees. Chi square tests indicated that males performed significantly better than females on perception and prediction, and that instruction significantly improved male performance on prediction and female performance on prediction and perception. It was concluded that females, if given instruction, could more closely approximate the performance of males on the horizontal water level task.


Slope of gradients for performance as a function of achievement motive, goal distance in time, and future time orientation.

It was predicted that (a) individuals high in motivation to approach success and low in motivation to avoid failure (approach-oriented) would increase their performance and (b) those with the opposite motivation constellation (avoidance-oriented) would decrease their amount of performance as a distant future achievement task (goal) approached in time. Furhter, it was assumed that individuals high in future time orientation (FTO) would perceive a distant future event (goal) as nearer in time than those who are low in FTO. This implies the hypotheses that (c) the slope of the positive goal gradient is steeper for those of the approach-oriented individuals who are low in FTO as compared with those who are high in FTO, and (d) the slope of the negative goal gradient is steeper for those of the avodiance-oriented individuals who are low in FTO as compared with those who are high in FTO. The results, based on 379 boys and girls (about 12 years old), supported hypotheses a and d, and left also some indications that supported hypotheses b and c.


Trends in powerlessness: a ten year follow-up.

This experiment tested the hypothesis that there would be a significant increase in powerlessness scores over a 10 year period. The sample was drawn from a population of college students originally tested in 1964. At the 10 year follow-up, all Ss had graduated from college and were either professionally employed (mostly as teachers) or engaged in child-rearing/home activities. The average age of the 1974 sample was 29 years and consisted of 70 females and 30 males. The test instrument was the adult version of Rotter's Internal-External (I-E) Locus of Control Scale which consists of 23 forced-choice items. There were no significant differences on total I-E scores over the 10 year period. However, with use of the Mirels two-factor scoring system, significant increases in social-political control were found. No significant differences in personal control were found. It was concluded that care should be taken in utilizing cross-sectional findings and that utilizing multidimensional scores suggests different results for previously published reports.


Problem-solving training groups for hospitalized psychiatric patients.

Small groups lasting eight sessions each and aimed at improving patient's interpersonal problem-solving skills were conducted for a total of 41 hospitalized psychiatric patients. Forty control patients received the same pre and posttests but notraining. Twenty-three patients participated in play-reading groups without problem-solving training (placebo condition). Three separate 3 by 2 repeated measures analyses of variance showed that hospitalization alone improved the patient's functioning on the criterion test of problem-solving, but the problem-solving training groups advanced the improvement significantly. More disturbed patients made only slightly greater gains than less disturbed ones. The hospital stay was significantly shorter for the experimental and the placebo groups than for the control sample.


Modification through modeling and reinforcement in leaderless groups.

This study compared the effects of modeling plus reinforcement (MR), reinforcement alone (R), and demand characteristics (D) on individual verbal output in a leaderless group discussion. Seventy-two male and female volunteers from undergraduate psychology courses (mean age 20.7 years) were assigned to three-person groups in the three conditions and participated in two 10 minute discussions. Ss who spoke the least in the first discussion were chosen as target persons (TPs). TPs in the R condition were reinforced for talking and punished for silence. TPs in the MR condition received the same treatment but were also exposed to a leadership modeling film. TPs in the D condition received no reinforcement, but were encouraged to become the group's leader. All conditions showed increases in verbral output, but the MR was superior to both the R (p less than .05) and D (p less than .01) conditions. The results were interpreted as consistent with Bandura's mediational theory of modeling.


The relationship of personality traits as measured in the questionnaire medium and by self-ratings.

The general purpose of the study was to determine (a)whether individuals tend to have an accurate perception of their personality, and (b)the manner in which an individual's personality (as measured by a personality questionnaire) affects self-ratings on the same traits. The Clinical Analysis Questionnaire (CAQ), Part 1, was administered to 98 males and female undergraduates. One week later, Ss were asked to self-rate themselves on the 16 personality traits measures by the CAQ, using a modified version of the 16PF Test Profile. High correlations between measured and self-ratings indicated that the instruments were measuring similar, but not identical, traits. Following a factor analysis of the intercorrelations, 12 factors were identified, representing the interrelationship between perception of self and measured personality traits.


The effects of instructions on self-disclosure.

In a study of the effects that instructions have on self-disclosure, two groups of male and female college students (N = 120) were asked to select items for discussion with a same sexed stranger under one of two sets of instructions: (a) Ss were asked to select items that they were interested in discussing or (b) Ss selected items they were willing to discuss. Results indicated that changing one word from "interested" to "willing" produced significantly higher potential disclosures in all Ss from low to high disclosers.


Mood and helping.

In order to test (a) whether helping someone puts the helper in a better mood and (b) whether people in a good mood are more likely than controls to help with a task maintaining their positive mood but no more likely to help with a task leading to a negative mood, 80 female undergraduates participated in a study in which they (a) had an interaction with a confederate (C) designed to put them in a good or neutral mood, (b) rated their mood, (c) rated some neutral pictures, and (d) were requested to rate some potentially elating or depressing pictures. Ss who were induced to help C or who were given candy by her rated themselves as feeling nicer than these having a more neutral interaction. Neither their interaction with C, the type of pictures they were ased to rate, nor their self-reported mood, with the exception of happiness, was significantly associated with number of pictures rated or time spent helping. Those rating the depressing pictures became more depressed than those rating the cheerful pictures. It was suggested that the lack of significant findings might be due either to the fact that the effect of a good mood on helping declines over time or to the fact that rating pictures was so enjoyable that it was not considered altruistic.


Racial prejudice, belief similarity, and human aggression.

Out of 66 undergraduates administered a scale designed to measure racial prejudice, 16 male Caucasians scoring above the median and 16 male Caucasians scoring below the median later interacted in a competition situation with an attitudinally similar or an attitudinally dissimilar black stimulus person. The competition situation was such that the Ss had the opportunity to aggress against their opponent using electric shock. The results indicated that highly prejudiced attitudes were related to high aggression scores. It was also observed that the attitudinal similarity variable interacted with the prejudice variable during the initial stages of the aggressive interaction.


The effect of increased information upon community perception of ex-mental patients.

Data are presented for 30 suburban homeowners, which suggest they respond differentially to three levels of severity when rating the concept ex-mental patients via the semantic differential technique after having been given descriptive information about typical symptoms and behaviors. This finding contrasts with those from a previous study of similar suburbanites which indicated nonindividuation among severity of illness levels under minimal information conditions. A more favorable perception of mildly ill ex-mental patients resulted from the exposure to more information.


The indication of sexual and aggressive similarities through humor appreciation.

Freudian theory and subsequent research indicate a connection between sexual and aggressive motivation. The present study investigated this proposed connection by examining humor preferences during an induced aggressive mood. Appreciation of neutral, sexual, and aggressive humor was examined under conditions of aggression arousal. A total of 90 male and 90 female university students participated in one of two 2 X 3 factorial designs that crossed arousal with humor type. Ss in arousal conditions rated all humor as funnier than Ss in neutral conditions, and sexual humor was rated as being funniest. Males and females showed complex significant differences in humor preferences.


Response bias and physiological reactivity.

Sixteen Ss were selected from a group of 30 adult males for low and high levels of physiological reactivity, as defined by several measures of electrodermal activity (EDA). They were subsequently tested on two occasions on a tone discrimination task in which confidence ratings were required. High EDA Ss discriminated a significantly greater number of tones, but this apparent superiority was not due to their superior sensitivity, but to a greater bias towards responding positively to signals. The results were discussed in relation to possible mechanisms mediating individual differences in response bias and physiological reactivity.


The effects of HCG, indomethacin, flufenamic acid and aspirin in the immature female rat.

Immature female rats (21 to 23 days old, 35 to 45 g) were injected subcutaneously with 2-5 i. u. HCG 18 hr before autopsy. Ovaries and uteri were removed; wet weight, dry weight and uterine protein content were determined. Ovarian and uterine weights, ovarian blood volume and uterine protein content were increased after HCG treatment. When immature female rats were pretreated with indomethacin, flufenamic acid or aspirin, the ovarian effects of HCG were inhibited: only slight increases in ovarian weight and blood volume were observed. Indomethacin attenuated the increases in uterine weight, and protein content, but neither flufenamic acid nor aspirin were effective in inhibiting these responses. The possible role of prostaglandins and of oestrogen as mediators of these responses is discussed.


Ultrastructural studies of semen abnormalities and Herpesvirus associated with cultured testicular cells from domestic turkeys.

Abnormal cells and macrophages found in white and yellow turkey semen were studied by electron microscopy. Yellow semen contained many abnormal cells, most of which were large and round or smaller and ellipsoidal. It was concluded that they were aberrant spermatids, with differentiation being more complete in the smaller cells. Only a few cells of the smaller type were detected in normal white semen. Macrophages were occasionally seen in white semen but were numerous in yellow semen. Phagocytic vacuoles of these cells contained structural elements of spermatozoa and abnormal spermatids. Virus particles were not detected in any of the seminal cells observed. Ultrastructure studies of cultured testicular cells obtained from several of the turkeys examined showed the presence of intranuclear Herpesvirus particles in germinal cells. Macrophages from the testicular cultures seldom were seen with intranuclear Herpesvirus, although these cells commonly were found with Herpesvirus particles and cellular debris contained within phagocytic vacuoles.


Neurophpophysial hormones and the emission of semen in rabbits.

To elucidate the importance of the neurohypophysial hormones for the emission of semen, several neurohypophysial peptides were tested in male rabbits and the sperm density in the ejaculates was determined. Besides oxytocin and vasopressin, vasotocin and one oxytocin analogue (de-amino1-oxytocin) were used. Only vasopressin, in a dose as low as 10 mU, increased the number of spermatozoa in the ejaculates. It is suggested that vasopressin is of physiological significance for the emission of semen, at least in rabbits.


The seminiferous tubules in dasyurid marsupials.

The morphology of the seminiferous tubules of dasyurid marsupials has been investigated in seven species. The tubules are large in diameter, ranging from 0-36 to 0-52 mm, and the total length of the tubules in the testis is small (less than 1 m). In dissected testes, most tubules were found to be in the form of simple loops and the number of loops ranged from one to four. Each loop had two openings into the duct draining the testis. There was only a single duct from the testis in the dasyurids examined. The large diameter, simple form and low number of tubules in the testis of these dasyurid marsupials make them unique among mammals which have been studied in this respect.


Methods of measuring swimming speed of spermatozoa.

Three basic approaches for determining the mean swimming speed of a suspension of microorganisms were compared, using bull and ram spermatozoa. Number fluctuation counting was performed automatically on a Quantimet 720 image analysing computer, the mean speed being obtained using 'probability after' statistics. The other two approaches were photomicrographic: number flux counting was performed on single photomicrographs; on the same photomicrographs, the mean speed was estimated from measurement of 'whole' and 'half' track lengths. These results were compared with each other and with the Quantimet results. The 'probability after' method was also compared, on additional samples, with cine-photomicrographic tracking. The mean speeds predicted by the 'probability after' method compared favourably with the other methods (range 68 mum/sec to 162 mum/sec). The results also suggested that, on single photomicrographs, measurement of 'half' track lengths or number flux counting were generally preferable to measurement of whole track lengths.


The effects of nutrition on the reproductive performance of Finn x Dorset ewes. I. Plasma progesterone and LH concentrations during late pregnancy.

Progesterone and LH concentrations were measured in the plasma of blood samples taken from forty-eight pregnant ewes on Days 100, 120 and 134 of gestation. The ewes, in two groups of twenty-four were maintained from Day 100 until parturition on two planes of nutrition which supplied daily energy and protein intakes of about 4-1 or 2-3 Mcal metabolizable energy and either 192 or 111 g digestible crude protein per ewe. Within the groups, the ewes carried one, two or three fetuses and the feed intake was adjusted according to litter size to produce a uniform nutritional state within the group. On Day 100, litter size affected the concentration of plasma progesterone (P less than 0-001), but had no effect on Days 120 or 134 when the ewes were fed according to litter size. The low feed intake however caused a significant increase in plasma progesterone concentrations. The LH concentrations showed no major changes during late pregnancy and no effect of nutrition or little size on the plasma hormone concentration was observed. It was concluded that the effect of litter size on plasma progesterone concentration recorded on Day 100 or gestation was partly mediated by level of nutrition.


The effects of nutrition on the reproductive performance of Finn x Dorset ewes. II. Post-partum ovarian activity, conception and the plasma concentration of progesterone and LH.

After lambing forty-five ewes were allocated to three groups, two of sixteen and one of thirteen ewes. The lambs of the two groups of sixteen ewes were weaned on Day 1 after lambing and the ewes were fed a diet of 100% (Group H) or 50% (Group R) of maintenance energy requirements. The thirteen ewes in the third group (Group L) suckled twin lambs and were fed freely. During the first 3 weeks after lambing, oestrus was observed for 11/16 (Group H) and 8/16 (Group R) ewes; of the ewes which had shown oestrus in the two groups, ovulation occurred in 5/8 and 5/7 respectively. Only 1/13 Group-L ewes showed oestrus and ovulated during the same period. The mean plasma concentrations of progesterone and LH were unaffected by the treatments and were around 0-4 and 1-5 ng/ml, respectively. Restricted feeding had no effect on oestrus, ovulation or the hormone levels during the oestrus cycle following synchronization. The onset of oestrus and the start of the preovulatory discharge of LH were 3 and 6 hr later, respectively, in the lactating ewes (Group L) than in those in Groups H and R. Ewes in Group L also had a higher ovulation rate, 2-8 +/- 0-2 versus 2-1 +/- 0-2 (P less than 0-05). Restricted feeding reduced the number of ewes lambing; only 1/11 ewes in Group R, considered to have conceived because of the presence of high progesterone levels 17 days after mating, subsequently lambed compared with 6/12 in Group H and 5/9 in Group L.


Abortifacient effects of Vibrio cholerae exo-enterotoxin and endotoxin in mice.

To study antifertility properties of microbial toxins, exoenterotoxin and endotoxin from Vibrio cholerae were injected intravenously into mice at different times during pregnancy. The two substances induced termination of pregnancy, but the patterns of abortifacient activity were different. Exotoxin terminated pregnancy in mice when administered between Days 4 and 10 of gestation, but abortifacient activity was reduced in animals more than 10 days pregnant; exogenous progesterone did not protect the pregnancies. Endotoxin was most effective in terminating pregnancy when injected after mid-gestation and the active principle was heat-stable; exogenous progesterone was not able to prevent the effects of endotoxin. Animals treated with endotoxin on Day 17 often gave birth to live young prematurely; indomethacin reduced the incidence of premature littering. The results demonstrate that exo- and endotoxins have antifertility properties and both appear to act on intrauterine targets rather than inducing progestin deficiency.


The frequency of aneuploidy in the secondary spermatocytes of normal and Robertsonian translocation-carrying rams.

A detailed analysis was made of the chromosomes in 1008 M II figures from three different types of heterozygous Robertsonian translocation-carrying rams (53,xy,t1; 53,xy,t3) and 225 M II figures from homozygous Robertsonian translocation-carrying rams (52,xy,t1t1; 52,xy,t3t3) and rams of normal karotype (54,xy). No hypermodal cells were recorded in either the normal or the homozygous rams, but from 4-5% to 9-2% of M II cells from the heterozygous rams were hypermodal. The heterozygous rams also produced a significantly higher level of hypomodal cells suggesting that, in addition to non-disjunction, lagging at anaphase I may have occurred. There were also distinct differences in M II aneuploid spermatocyte frequency between heterozygous versus normal and homozygous rams. Fewer balanced translocation X-carrying M II cells were recorded than expected in three of the four 53,xy,t2 rams. This coincides with mating data which suggest that 26,x,t2 gametes may occur less frequently than expected. Since ewes of normal karotype mated to 53,xy,t rams conceive to first service at a rate equal to or better than normal mating groups, and because no blastocysts with unbalanced karotypes associated with the t1 translocation have been recorded, it is suggested that only euploid spermatozoa are involved in fertilization. In the sheep, aneuploid spermatocytes probably degenerate before sperm maturation.


The fine structure of the human endometrial ciliated cell.

Sixty-eight histologically normal specimens from all stages of the menstrual cycle were examined during an ultrastructural study of the human endometrial ciliated cell. The 'clear' ciliated cells found initially were seen to become at first dense and then secretory. These changes are advanced as an explanation to account for the previously observed reduction in frequency of the ciliated cell during the luteal phase. The possibility of an hormonal control mechanism is discussed.


Effects of maternal blood loss on embryonic and placental development in the rat.

The effects of acute loss of maternal blood on embryonic and placental development was examined in 50 rats on Days 8 or 9 of gestation. Blood was withdrawn from conscious, cannulated rats over a 1-min period at 1-0 or 2-0 ml/100 g body weight. These degrees of blood loss were expected to produce a mild (about 50%) and severe (about 80%) reduction in uterine blood flow, respectively, for at least 15 min. There was no evidence that loss of blood affected either fetal survival and malformation rates or fetal weights and sex ratios. The anaemia resulting from haemorrhage lasted no longer than 6 days. Placental weights were 11% higher in rats losing 2-0 ml blood/100 g than in controls (P less than 0-05). It appears that the 8- or 9- day rat embryo is highly resistant to the partial reduction in uterine blood flow, maternal anaemia and other possible challenges induced by maternal loss of blood at levels sufficient to affect the mothers.


Free N-acetylaminosugar in the seminal plasma of eutherian mammals.

The seminal plasma of seven eutherian species, including man, was examined for the presence of free N-acetylaminosugar. Only man had appreciable levels of N-acetylaminosugar in the semen (37-1 mg/100 ml), but in all cases this free N-acetylaminosugar was probably the result of breakdown of polysaccharides by semen glycosidases. High levels of free N-acetylaminosugar thus appear to be peculiar to marsupials.


The absorption by boar spermatozoa of zinc bound to low molecular weight ligands.

Most of the zinc accumulated by boar spermatozoa at 4 degrees C from seminal plasma appears to arise from the low molecular weight zinc ligands. Zinc added to semen in low concentrations (0-1 to 0-6 mM) is preferentially absorbed by the spermatozoa, particularly at 4 degrees C.


Reproduction in the ferret. I. The effect of ovariectomy on the course of gestation.

The role of the ovaries in the maintenance of pregnancy was studied in the ferret. Ovariectomy at the time of implantation showed that some embryos survived for 7 days after the operation but all were destroyed after 10 days, although the trophoblast continued to grow at a much faster rate than normal. Ovariectomy performed after implantation showed that no fetal development occurred when the ovaries were removed at Day 21 post coitum, but that fetuses developed for an appreciable length of time in animals ovariectomized on Days 23 to 27 post coitum. Ovariectomy in late gestation resulted in speedy expulsion of the fetuses. An increase in the placenta:fetus ratio did not alter the response to ovariectomy in late gestation. The uteri in all ovariectomized animals showed progestational endometria when examined shortly after explusion of the fetuses.


Embryonic mortality during the pre- and post-implantation periods of pregnancy in mature mice after superovulation.

Sexually mature mice were stimulated to superovulate by giving exogenous gonadotrophins at known stages of the oestrous cycle. Untreated animals which ovulated spontaneously served as controls. The number of oocytes ovulated by each female was estimated from counts of the number of CL of pregnancy, and the incidence of embryonic mortality during the pre- and post-implantation stages of pregnancy was assessed from the number of zygotes recovered from the reproductive tract at 2-0 and 4-0 days post coitum and of conceptuses examined at 7-5 and 11-5 days post coitum. The mean number of oocytes ovulated by treated animals was 39-54, compared with 12-80 in controls: in mice which had superovulated, 44% of the ova were lost before implantation compared with about 10% in the controls. Further losses occurred about the time of implantation and at mid-pregnancy and thus the number of embryos classified as normal rarely exceeded the maximum found in controls. Death at mid-pregnancy seemed to be preceded by developmental retardation. The possibility that genetic and environmental factors play a role in embryonic loss after superovulation is discussed.


The development of the mouse ovary and its response to exogenous gonadotrophins.

Immature mice aged 14 to 49 days were treated with a single injection of 4 i.u. HCG, or 3 i.u. PMSG followed 48 hr later by 2 i.u. HCG. After treatment with HCG alone the number of oocytes which were ovulated rose gradually from Day 21 to Day 28 and then remained constant, while the combined PMSG+HCG treatment induced a peak response between Days 24 and 28. The percentage of animals responding also varied with age and treatment. After the combined PMSG+HCG treatment, 90% of the animals ovulated on Day 21, while a similar proportion was not achieved in response to HCG alone until Day 32. The variation in response with age and treatment was related to follicular development within the ovary.


Epithelial cell death in the oil-induced decidual reaction of the pseudopregnant mouse: an ultrastructural study.

Arachis oil instilled into the uterus of sensitized mice was localized mesometrially or, more commonly, antimesometrially, suggesting that the uterus is polarized in its capacity to respond since implantation chambers only form antimesometrially. Epithelial breakdown occurred only within the 'implantation chabmer', but cell death took place more rapidly than in normal pregnancy and was complete at only 5 to 9 hr after the Pontamine Blue reaction. Between 19 and 43 hr after oil instillation, the antimesometrial epithelial cells lost contact with each other and initially were characterized by distended rough endoplasmic reticulum and Golgi body, lipid droplet accumulation and ribosome segregation. At a later stage of deterioration, epithelial cell contents were scattered into the uterine lumen where polymorphonuclear leucocytes and monocytes were also found, probably involved in ingesting the cellular debris. There was no evidence of increased size of lysosomal dense bodies or of the formation of autophagosomes in dying epithelial cells; suggesting that the mechanism of epithelial death in the oil-induced reaction is not identical to that of normal pregnancy.


Sexual receptivity and oestrus in the white-toothed shrew, Crocidura russula monacha.

In common white-toothed shrews, the vaginal smear was an inadequate indicator of receptivity. Nucleated epithelial cells usually predominated and most matings took place when the smear was of this type. Cornified cells in the smear in infrequent. Mating tests showed that virgin females 2 to 4 months old, were unreceptive for extended periods. Willingness to mate increased gradually with the age of the female. Females were receptive throughout pregnancy, suggesting a continuous secretion of oestrogen during gestation. There was a post-partum oestrus whether or not the young of the litter were being suckled, and an oestrus at the end of lactation. During mid-lactation, females were in a state of low receptivity, whether or not they were suckling.


Testis growth and plasma LH concentration following hemicastration and its relation with female prolificacy in sheep.

The mean testis diameter of 20- to 25-week-old Blackface, Finn and Merino rams was ranked in the same order as the ovulation rates of females of their breeds. The removal of one testis at 12 or 16 weeks of age resulted in hypertrophy of the remaining testis. The relative increase in testis growth following hemicastration was greatest in the Merino rams (72%), least in the Finns (42%) and intermediate in the Blackfaces (57%), so that it was inversely related to their breed ovulation rates. This hypertrophy was associated with increases in the concentration of plasma LH in all breed types. The results indicate that differences in testis growth rate are associated with differences in gonadotrophic stimulation rather than in intrinsic growth potential, and it is postulated that these may arise from breed differences in sensitivity to negative feed-back from the testes.


Secretion of human chorionic gonadotrophin by the early placenta in Vitro.

The secretion in vitro of HCG and proteins was studied in fragments of placenta from women in the first trimester of pregnancy by a pulse-chase system. A 10-min pulse with [3H]leucine was used. It was concluded that the approximate half-time of release of HCG was 150 min. Proteins precipitable with trichloroacetic acid had a bi-exponential pattern, the half-times of release being 100 and 270 min. These rates of release indicate that the HCG produced by the early placenta was rapidly passed into the circulation rather than stored.


Spatial distribution of chromosomes 1 and Y in human spermatozoa.

The positions of chromosomes 1 and Y inside human spermatozoa were determined by differential staining techniques. In 85/100 cells the two chromosomes were in close contact and in association with a vacuole. This observation is in contrast to previous findings for chromosome No. 9 and the Y-chromosome whose positions do not appear to be correlated.


Sites of production of fructose and citric acid in the accessory sex glands of the male musk shrew, Suncus murinus.

The main source of citric acid in the accessory sex glands of the musk shrew (Suncus murinus) was the prostate and fructose was abundantly produced by the ampullary glands.


Release of prostaglandin F-2alpha during foaling in mares.

The concentrations of PGF-2alpha in the peripheral blood of five foaling mares were measured by radioimmunoassay. Low levels of PGF-2alpha were detected as early as 1 week before foaling in two of the mares. These levels increased steadily, reaching a peak (1-74 +/- 0-44 ng/ml) during fetal expulsion. A relatively high PGF-2alpha level was found in samples collected 60 min after foaling.


The function of the growing follicle.

The follicle plays a major role in the dual function of the ovary--oocyte maturation and release and steroidogenesis required for regulating its own growth and providing the proper environment in reproductive organs for the transport of gametes and nidation. Some aspects of how follicles attain their functional competence following a series of developmental changes are discussed. The presentation is based on data obtained mainly in rodents in which follicular development occurs postnatally. The peak activity of follicular growth occurs during the 1st week of life, but not until the 5th day is follicular development clearly dependent upon gonadotrophin stimulation. The formation of the theca layer and zona pellucida, differentiation of the vascular system and competence to respond to gonadotrophins are acquired during the 2nd week. FSH alone is primarily responsible for granulosa cell proliferation and the integrity of the granulosa cell membrane, but has little differential effect on steroidogenic enzymes. Synergism of FSH and LH promotes an enrichment of the theca layer, enhancement of vascular development and antrum formation, and induces a marked differential stimulation of 20alpha-hydroxysteroid dehydrogenase, aromatizing and cholesterol side-chain cleavage systems. The number of gonadotrophin receptors on granulosa and theca cells increases with follicular development. Steroids secreted by the ovary seem to modulate follicular growth, not only by effects upon FSH and LH release but also by a local influence within the ovary. A number of physiological events related to follicular function are explained according to these observations.


Renal biopsy in pregnancy-induced hypertension.

Percutaneous renal biopsy, introduced 20 years ago, has revolutionized our understanding of many diseases affecting the kidney. In studies performed in nonpregnant subjects substantial progress in defining the mechanism, prognosis and treatment of a host of renal diseases was achieved by correlating clinical findings and renal function with light, electron and immunofluorescent microscopy. In the early 1960's investigators described the renal lesions associated with preeclampsia and made initial clinicopathological correlations, but relatively few studies combining light, electron and immunofluorescent findings in pregnant women have appeared to date. This is because clinical circumstances rarely justify even the minimal risks of biopsy during gestation, and after the disease has regressed, nephrology consultation is not requested in the puerperium. In addition, a report of excessive bleeding and other complications in gravidas, although not encountered by other groups (and personal experience of the authors), has contributed to the lack of enthusiasm for renal biopsy on obstetrical services and to the belief that this procedure is not advisable both during gestation and the immediate puerperium. This article reviews the renal morphology of preeclampsia and described those aspects of it in which current knowledge is still incomplete. Indications, benefits, and risks of kidney biopsy during pregnancy or puerperium will be discussed, with emphasis on the prognostic information to be expected from the procedure which may help in predicting the outcome of future pregnancies.


The treatment of gestational hypertension.

The development of a logical and physiologically sound approach to the management of gestational hypertension presents a formidable challenge to both obstetrician and internist. The maternal and fetal risks and sequelae are well known and significant. Therefore, understanding the pathophysiology of the particular hypertensive syndrome or disease being treated is of great importance if a rational approach to treatment is to be accomplished. In this discussion we will present the pharmacology of the various antihypertensive agents currently being used, followed by a brief discussion of our current concept of the pathophysiology of the three major types of hypertension seen during pregnancy and finally by our suggested management.


Prevalence of ankylosing spondylitis and its association with HL-A 27.

The close relationship between ankylosing spondylitis and the presence of the transplantation antigen HL-A 27 is well recognized. An attractive explanation for this has been that the gene coding for this antigen exists in marked linkage disequilibrium with an abnormal immune response gene. We have suggested, in contrast, that HL-A 27 may have a more direct importance because of a defective epistatic interaction between the gene coding for this antigen and a distinct disease susceptibility gene for AS, which may therefore be situated some distance from the major histocompatibility complex.


Size distribution of lymphocytes in juvenile rheumatoid arthritis.

The diameters of circulating peripheral lymphocytes were measured in 28 children with juvenile rheumatoid arthritis. These were compared with lymphocyte measurements in 68 normal children, 19 children with asthma, and 12 children with cystic fibrosis. The average diameter of lymphocytes in normal children was found to be 11.2 microns. In contrast, the average diameter of lymphocytes in juvenile rheumatoid arthritis was 12.7 microns (P less than 0.0001). There were more lymphocytes with a diameter of 13 to 15 microns in children with juvenile rheumatoid arthritis than in normal children.


Experimental immune arthritis: host factors.

An experimental chronic mono-arthritis was induced in rabbits using adjuvants and bovine serum albumin. The results suggest that unidentified host factors (possibly genetic) influence the induction of delayed hypersensitivity to the antigen. The data further show a clear correlation between systemic cell mediated immunity and chronic synovitis. When this condition is absent, there is a poor correlation between the humoral response and the arthritis. The results make difficult the interpretation of local immune complex deposition as the sole, chronic phlogistic stimulus. (J Rheumatol 2: 373-383, 1975).


Decreased concentration of free histidine in serum in rheumatoid arthritis, an isolated amino acid abnormality not associated with generalized hypoaminoacidemia.

The serum concentrations of 12 free amino acids (alanine, arginine, glycine, histidine, isoleucine, leucine, lysine, phenylalanine, serine, threonine, tyrosine, and valine) were measured in 26 patients with rheumatoid arthritis and in 12 control subjects. Patients with rheumatoid arthritis had a low serum histidine concentration (P equals 0.002) but no abnormality of any other amino acid concentration or of the combined concentration of the measured amino acids, excluding histidine. These data and 22 other reported studies provide strong evidence for the presence of hypohistidemia, not associated with generalized hypoaminoacidemia, in patients with rheumatoid arthritis. (J Rheumatol 2: 384-392, 1975).


The origins and relative distribution of polysaccharidases in rheumatoid and osteoarthritic fluids.

Three lysosomal polysaccharidases were measured in synovial fluid (SF) and serum from rheumatoid (RA) patients, SF from osteoarthritic (OA) patients, and serum from healthy volunteers. (1) There was no correlation between the enzyme levels and white cell counts in the SF. (2) beta-glucuronidase and beta-N-acetylglucosaminidase were markedly elevated in the SF of RA as compared to OA. (3) beta-glucuronidase and beta-N-acetylglucosaminidase levels in the SF of RA correlated well with each other but not with hyaluronidase. (4) beta-glucuronidase and beta-N-acetylglucosaminidase levels were higher in the SF of RA than in the corresponding serum, while the converse was true for hyaluronidase. (5) Hyaluronidase levels were significantly higher in RA serum than in normal serum. These results suggest that the synovial membrane may be the source of beta-glucuronidase and beta-N-acetylglucosaminidase, while hyaluronidase is derived from a source remote from the joint via the serum. This source of hyaluronidase may be the liver. (J Rheumatol 2: 393-400, 1975).


Chrysotherapy: pharmacological and clinical correlates.

Relationships between gold administration and serum gold content were observed in 56 RA subjects receiving up to five years of weekly chrysotherapy. Wide fluctuations in serum gold responses to standard 50 mg IM injections were noted. Individual adjustments to dosage schedules were made as dictated by patient serum gold responses. Enhanced clinical and laboratory response was prolonged with higher sustained serum gold concentration greater than 300 mug per cent. Maintaining serum levels greater than 300 mug per cent is postulated to facilitate access of gold to "effector sites" within the deeper compartments by providing higher sustained gradients between superficial (blood) and deeper body compartments. The complexity of the system of effector sites responsive to gold and their divergent location within the body likely affects the accessibility of the agent for these sites; hence, affecting the correlation between gold levels and therapeutic response. The application of pharmacokinetic principles in chrysotherapy, nevertheless, provides the basis for optimizing accessibility of the agent and the therapeutic response. (J Rheumatol 2: 401-410, 1975).


Irreversible bone marrow failure with chlorambucil.

Two cases of irreversible bone marrow failure are described, one with rheumatoid disease and one with systemic lupus erythematosus. Each case was associated with prior chlorambucil administration, effective in controlling the clinical manifestations (total dosage 398 and 1,764 mg respectively). The irreversibility of the bone marrow depression in the two cases presented stands in contrast to published assurances that chlorambucil-associated leukopenia is dose-related and readily reversible. The cases illustrate that chlorambucil therapy should not be continued after initial leukopenia, until peripheral counts or marrow cellularity has returned to normal. Titration of drug dosage and leukocyte count, as frequently employed with cyclophosphamide and other alkylating agents, must be presumed hazardous. Additional studies are needed to determine if irreversible bone marrow depression is dose-related or idiosyncratic.


Avascular necrosis and its relation to lipid and purine metabolism.

Serum uric acid, triglycerides, cholesterol, and lipoprotein levels were determined in 35 patients with primary avascular necrosis of the femoral head. The results were compared with a control group and a group of gouty patients. Frequency distribution of the data in the three groups was found to be of the log normal type, and the statistical calculations were performed after log transformation of the serum values. Compared to the control group, a significant increase in the levels of triglycerides, cholesterol, pre-beta-lipoprotein, and uric acid were found in the patients with avascular necrosis. No significant difference was observed between lipid and lipoprotein levels in gout and avascular necrosis, although the serum uric acid was higher in the gouty patients. In contrast to the findings in gout, the uric acid levels did not correlate with the lipid or lipoprotein fractions in patients with avascular necrosis. There were no statistical differences between lipid, lipoprotein and uric acid levels in patients with avascular necrosis receiving corticosteroids or using alcohol, as compared with those not taking these drugs. It is concluded that avascular necrosis of bone complicating longterm use of steroids or alcohol is not induced directly by the two drugs, but that the initiating event may lie in lipid disturbances.


The pharmacology of hypouricemic effect of benzbromarone.

The hypouricemic effect of benzbromarone has been investigated in six subjects. Benzbromarone increased urate: creatinine by 371 per cent over control values at two to four hours after administration. Over a 24 hour period, the mean serum uric acid decreased from a control value of 7.8 +/- 0.8 to 4.3 +/- 0.6 mg/dl. This uricosuric effect was completely reversed by pyrazinamide, partially inhibited by acetylsalicyclic acid and sulfinpyrazone, and was not accompanied by an elevation of the creatinine clearance or an inhibition of urate binding to plasma protein. In vitro studies showed only 22 per cent inhibition of urate binding by benzbromarone five muM, a concentration which is transiently reached in man. Kinetic studies of human liver xanthine oxidase demonstrated non-competitive inhibition with variable hypoxanthine and a Ki slope of 8.5 muM. The Ki slopes for benzarone and allopurinol were 19.0 muM and 0.05 muM respectively. There was no elevation of the urinary oxypurines following benzbromarone ingestion. These observations suggest that only the renal tubular activity of benzbromarone is relevant to its hypouricemic effects in man. (J Rheumatol 2: 437-445, 1975).


Pulmonary manifestations of ankylosing spondylitis.

Chest radiographs of 39 patients with ankylosing spondylitis were studied. Three showed apical pulmonary fibrosis, two with cavitary lesions. Other known causes of lung disease were excluded. Symptoms and roentgenographic evidence of spondylitis were present for many years prior to the onset of pulmonary symptoms, which variably included shortness of breath, cough, hemoptysis, pleuritic chest pain, fever, and chills. Apical pulmonary lesions of unknown cause were absent in 53 age, sex, and racematched osteoarthritis control patients. The findings suggest that apical pulmonary fibrosis may be an extra-skeletal manifestation of ankylosing spondylitis, the frequency of which approaches that of spondylitic heart disease.


A histochemical study of cervical motor neurons and the posterior latissimus dorsi muscle in normal and dystropic chickens.

A chromatolysis study, 14 to 21 days following denervation, showed the spinal cord representation of the nerve to the posterior latissimus dorsi muscle to be in the ventrolateral cell column between cervical ganglia 14 and 15. to characterize cevical neruos nt undergoing chromatolysis, histochemical stuies were done the cords of additional nondenervated animals. Staining reactions for beta-hydrocybutyrate dehydrogenase, succinic dehydrogenase and cholinesterase did not reveal any quantitative differences between motor neurons in cervical segments 14 and 15 of normal and dystrophic birds. Motor neurons are positive for beta-hydroxybutyrate dehydrogenase and succinic dehydrogenase, but the surrounding neuropil is positive for the latter only. No pseudocholinesterase activity is found in the ventral horn cells, but true cholinesterase is present in most of the neurons...


Smooth muscle cells in the rat testicular capsule: a developmental study.

This study of the postnatal development (from 1 to 60 days) of smooth muscle elements in the rat testicular capsule has demonstrated that while such elements are identifiable by light microscopy at 30 days, myocytes are present at birth as seen by electron microscopy. The differentiation of smooth muscle from birth to 30 days has been described, by which time it is of adult morphology and content. Perhaps significantly, it is at 30 days that the testis achieves a scrotal position, although sexual maturity does not occur until about 60 days. Presumably, at 30 days the testicular capsule of the rat is capable of the spontaneous contractions which are known to occur in the adult and which are assumed to aid the transport of non-motile spermatozoa from the testis to the spididymis. The presence of occasional striated muscle fibers in the rat testicular capsule as reported previously has not been confirmed by this investigation, although their possible origin is discussed.


Tables of critical values for examining compositional non-randomness in proteins and nucleic acids.

A binomially distributed statistic pchi2i is defined which in conjunction with a set of critical tables permits, for peptides or proteins of arbitrary lengths, a well-defined answer to the question: Does the proportion of a particular amino acid iota present in that protein deviate significantly from random expectation? An analogous statistic is defined for nucleic acids. This statistic is simply related to the classical chi-squared test. The classical chi2 and the pchi2i are supplementary in that the former permits one to determine that a non-randomness in amino acid composition exists in a protein, while the latter permits one to localize that non-randomness to particular amino acids. The pchi2i statistic takes into account explicity the compositional fluctuations imposed by the finite length of proteins. The tables are more exact than any hitherto existing, and require no intermediate calculations for their use: from the direct experimental measurement of the number of residues of amino acid iota, one immediately reads from the tables whether the number observed is within random expectation or not. These statistics are used to analyze eight proteins of diverse length, function, and origin in an accompanying paper.


Homologies of ribosomal RNA nucleotide sequences in monocots.

Competitive hybridization among ribosomal RNA was used to estimate homologies of nucleotide sequences in monocots. Homologies have been measured with respect to Allium cepa (Liliaceae) and Zea mays (Graminaceae). It was found that nucleotide sequences are highly conserved within Liliaceae, while some divergences were found within Graminaceae.


Speculations on the origin and evolution of metabolism.

An autotrophic origin of metabolism is described, which requires clays, transition state metals, disulfide and dithiols, U.V. and cyanide ion. A general scheme is proposed, involving the fixation of CO2 and N2, for the evolution of intermediary metabolism based on the evolution of a complex system from a simple one. The basic conclusion is that metabolism could have evolved from a simple environment rather than from a complex one.


The charge-state model of protein polymorphism in natural populations.

Routine electrophoretic surveys for genetic variation in natural populations depend primarily upon detecting differences in the net charge carried by a protein. We have calculated the proportion of base substitutions which would yield an electrophoretically detectable mutant protein, and the relative mutation rates among different chare classes, under a variety of simplifying assumptions. These calculations indicate that: (i) only 25 per cent of all single base mutations would lead to a charge change on a protein molecule. (ii) five distinct classes of electrophoretic variants can be generated from a specified protein by single base substitutions. (iii) the relative mutation rates differ markedly among the different charge classes which can be generated by single base substitutions. The estimates of the proportion of electrophoretically detectable mutant proteins and relative mutation rates among charge classes were relatively robust to changes in assumptions concerned with the kind and site of base substitutions and the amino acid composition of the protein.


Evolution of the haem-haem interaction in vertebrate haemoglobins - a hypothesis.

A hypothesis about the evolution of the haem-haem interaction in haemoglobins has been formulated on the basis of available functional and structural data. It emerges that this cooperative muchanism is not necessarily due solely to the higher levels of protomer aggregation, because it occurs only in haemoglobins having the distal histidine. It is thus proposed that this amino acid residue might have had a significant role for the development of low-oxygen-affinity haemoglobins in vertebrates.


Compartmentalization of amino acids in surfactant aggregates. Partitioning between water and aqueous micellar sodium deodecanoate and between hexane and dodecylammonium propionate trapped water in hexane.

Cationic amino acids, arginine and lysine partition differentially from water into aqueous micellar sodium dodecanoate. Conversely, partitioning of serine, glycine, aspartic acid, glutamic acid, threonine, alanine, proline, valine, leucine, phenylalanine and isoleucine do not vary appreciably. Partitioning from neat hexane into dodecylammonium propionate trapped water in hexane is, however, dependent upon both electrostatic and hydrophobic interactions. These results imply that the interior of dedecylammonium propionate aggregates is negatively charged and is capable of hydrogen bonding in addition to providing a hydrophobic enviroment. The solubilities of amino acids in neat hexane substantiate the previously derived amino acid hydrophobicity scale. Relevance of partitioning in these systems to the postulated selective amino acid compartmentalization is discussed.


Detecting evolutionary trends from molecular data. 1. Some measures of compositional nonrandomness.

The measures of compositional nonrandomness to be discussed as to their physical significance and to their power of detecting evolutionary significant variations are (see article)(pi a priori probability for amino acid i, ni its number of occurrences in a protein of length L). As a concrete example, the pi are here supposed to represent equal frequencies of all non-stop codons. For each quantity, four levels are defined: The base level, with optimal (i.e. minimal nonrandomness) composition, admitting non-integer values of ni; the integer level with optimal integer composition; the noise level, represented by a typical random cain; and the real protein level. On all these levels, S, which is the measure with the most direct physical sense, shows the smoothest behavior with the smallest relative fluctuations and thus the highest resolution.


Abnormal profile of human nucleolytic activity as a test for cancer.

Serum samples from patients with various malignancies including acute nonlymphocytic leukemia (ANLL), brain tumor (BT), Hodgkin's disease (HD), and non Hodgkin's lymphoma (NHL) were evaluated for nucleolytic activity against six synthetic polynucleotides: polyadenylic acid, polyuridylic acid, polycytidylic acid, polyguanylic acid, polyadenylic-polyuridylic acid, and polyguanylic-polycytidylic acid; The enzyme activity was determined spectrophotometrically by following the degradation of substrate to acid-soluble nucleotides. Most patients had elevated serum RNase activity at the 95% confidence level when compared to 30 controls. Included in this group were 67% of patients with ANLL, 46% of patients with BT, 73% of patients with HD, and 67% of patients with NHL. These data confirmed the earlier suggestion that elevated serum nuclease activity is found in patients with neoplastic disease. However, whether or not a serum was identified as abnormal depended on the substrate used in the assay; this underscored the need to test samples against a variety of polynucleotides. Alterations in serum nucleolytic activity represent an important marker of neoplastic disease and can serve as the basis for a useful clinical screening device.


Adriamycin-induced chromosome aberrations in human fibroblasts.

Adriamycin (AM) induced chromosome lesions and cell division delay in human foreskin fibroblasts. Cells treated with 0.01, 0.03, and 0.05 mug AM/ml culture medium for 1 hour and evaluated 5-12 hours post treatment exhibited a wide spectrum of cytogenetic injuries, ranging from moderately damaged metaphases with predominantly simple chromatid-type lesions to heavily damaged metaphases with chromosome stickiness and fragmentation. In moderately damaged metaphases that could be scored for specific types of aberrations, we observed a paucity of chromatid exchanges and chromosome-type lesions even in cultures having a very high frequency of breakages. Further, the distribution of breaks among chromosomes within groups A-G appeared to be random, which suggested that the drug does not show breakage specificity in human fibroblasts; The number of heavily damaged metaphases increased with an increase in concentration of AM and with longer periods of recovery.


Incidence of childhood cancer in Finland.

Between 1953 and 1970, 2,605 malignant tumors in children under 15 years of age were reported to the Finnish Cancer Registry, a population-based registry that covers the whole country (population, 4.6 million). The mean annual age-adjusted incidence rates per million were 128 in males and 108 in females. The most common neoplasms were leukemia (age-adjusted incidence rates, 43.7 in males; 34;7 in females), brain tumors (26.4 in males, 22.8 in females), renal tumors (10;0 in males, 9.1 in females), lymphomas (10.8 in males, 5.3 in females), and bone tumors (5;3 in males, 5.1 in females). This distribution is roughly the same as the observed in many other white populations. However, the incidence rates of leukemia, lymphomas, neuroblastomas, and soft-tissue tumors were somewhate lower than figures reported in the Third National Cancer Survey of the United States.


Change of antigenic expression on rat tumor cells after their transplantation.

Antigenic expression of 3-methylcholanthrene-induced transplantable fibrosarcoma KMT-17 cells was investigated in relation to days after ip transplantation. Cytotoxicity tests with antiserum against tumor-associated surface antigen of KMT-17 cells revealed that cytotoxic sensitivity and absorbing capacity decreased after transplantation, but they increased when other normal rats were given transplants of tumor cells. A decrease in the sensitivity was observed when immunosuppressively irradiated rats were given tumor transplants. Tumor cell density in the abdominal cavities of rats directly and absorbing capacity of KMT-17 cells to antiserum against the histocompatibility antigen did not change after transplantation. The possible mechanisms of antigenic change of KMT-17 cells were discussed.


Effects of levamisole on in vivo and in vitro murine host response to syngeneic transplantable tumor.

The effects of levamisole were studied in vivo and in vitro on two murine tumors, B16 melanoma and adenocarcinoma 15091, syngeneic to the mouse strains used. Administration of levamisole before tumor transplantation enhanced the early appearance of neoplasms but did not affect the overall incidence or course of tumor growth as compared with that observed in controls given saline injections or animals given levamisole with lethally X-irradiated tumor cells. Administration of the drug 1 day before iv injection of tumor cells significantly reduced the incidence of pulmonary nodules, but if the drug was given 3 or 5 days before tumor challenge, the incidence of nodules was increased. Lymphocytes or macrophages from normal mice given levamisole had no effect on tumor cells in vitro, whereas lymphocytes incubated with levamisole in vitro enhanced tumor cell growth. When lymphocytes and tumor cells were mixed in vitro, lymphocytes from animals treated with the drug formed larger multicell clumps with tumor cells than did those from normal controls. We concluded that levamisole did not protect the mice against the tested tumors.


Potentiation by carbon tetrachloride of the immunosuppressive effects of fibrosarcoma and toxic material produced by fibrosarcoma cells.

SaD2-AG fibrosarcomas growing in DBA/2 mice caused nonspecific immunodepression. Injection of soluble material produced by cultured SaD2-AG cells into normal DBA/2 recipients caused nonspecific immunodepression and signs of systemic toxicity. These in vivo effects were enhanced by prior treatment of the recipients with carbon tetrachloride (CCl4). In contrast, material released by syngeneic fibroblasts was neither immunosuppressive nor toxic to normal mice or mice previously treated with CCl4. A soluble toxic material released by the fibrosarcoma cells may be responsible for at least some of the systemic effects of localized SaD2-AG tumors growing at a site not involving vital structures, and a protective host mechanism whose maximum capacity can be decreased by the administration of CCl4 may minimize the toxic effects of the cancer-derived material.


Data on the action spectrum for ultraviolet carcinogenesis.

When 300, 310, or 320 nm monochromatic UV energy was given to albino mice in amounts proportional to its erythemal effectiveness, skin tumors developed on the exposed ears of the mice at approximately the same time and the same rate in all three groups. Thus the long wavelength limit of the carcinogenesis action spectrum paralleled that of the erythema action spectrum. No tumors were found in mice exposed to a 290-nm UV wavelength nor in those exposed to low dosages at 310 nm. All tumors observed in the group exposed to 300 nm were squamous cell carcinomas; 3 sarcomas and 5 squamous cell carcinomas were seen with the more penetrating doses of a 310-nm UV wavelength.


Cell-mediated immune responses to transplanted tumors in mice chronically exposed to cigarette smoke.

C57BL and BALB/c mice were exposed to fresh cigarette smoke for 7-8 minutes per day for varying periods up to 30 weeks before subcutaneous or intratracheal inoculation of viable tumor cells. The growth rates of subcutaneous tumors in the mice exposed to smoke were significantly higher than those of controls and more lung metastases were noted. Enhanced tumor growth rates in the respiratory tracts of smoke-exposed mice were evidenced by the markedly increased death rates in these animals after the intratracheal inoculation of tumor cells. Increased tumor growth rates in mice that inhaled smoke were assoicated with depressed tumor-specific cytotoxic responses in both spleens and regional lymph nodes. Short-term exposure (10 wk) of mice to cigarette smoke resulted in decreased tumor growth rates concomitant with enhanced cytotoxic responses.