In vitro profile of some opioid pentapeptide analogues.

The opiate agonist potency of thirteen synthetic enkephalin pentapeptides has been examined on the electrically stimulated guinea pig ileum and mouse vas deferens preparations in comparison with methionine and leucine enkephalins, beta-endorphin and normorphine. Their antagonism by naloxone (Ke) was also assessed on each preparation. Our findings are compatible with, and are discussed in the context of, the hypothesis that these preparations possess at least two populations of receptors.


Evidence for an endogenous factor interfering with 3H-diazepam binding to rat brain membranes.

An in vitro "receptor" binding assay has been used to search for an endogenous compound which possibly interacts with benzodiazepine receptors in brain. Such an endogenous 3H-diazepam binding inhibitory factor (DIF) has been found. This compound is unevenly distributed in brain and in various peripheral organs. The partially purified compound appears to have a low molecular weight (below 500) and is not inactivated by proteolytic enzymes.


Postsynaptic effects of 4-aminopyridine in the sixth abdominal ganglion of the cockroach.

The synaptic action of 4-aminopyridine (4-AP) was studied in the sixth abdominal ganglion of the cockroach Periplaneta americana L. The drug 4-AP did not modify the affinity of cholinergic receptors. At concentrations above 10(-4)M, 4-AP depolarized the postsynaptic membranes even after blockage of muscarinic and nicotinic receptors by antagonistic substances.


Temperature response to morphine in paralyzed cats.

Cats, sedated and paralyzed, showed a significant increase in body temperature after intravenous injection of morphine while animals with additional spinal blockade (C3) from injection of 2% lidocaine solution, did not. The results suggest that motor activity is not necessary for morphine-induced hyperthermia in the cat, as had been suggested in the literature.


Effect of intrauterine growth on erythropoiesis.

Erythropoietic activity, as reflected in the reticulocyte count and the incorporation of 59Fe into red cells, was studied in relation to intrauterine growth of rabbit fetuses during the last third of the period of gestation. Radioiron (10 microci) was administered by i.v. injection into the mothers and placental transfer to the fetuses. The fetuses were extracted after 48 hours. The amount of radioiron received by each individual fetus was determined by whole body counting. Radioactivity in red cells was determined and calculated as a percentage of the dose received. From day 21 to day 31 of gestation, the hemoglobin concentration increased by a factor of 1.5, from 8 to 12.2 g/100 ml, while the body mass increased by a factor of 7, from 6.6 to 47.5 g. During the same period the rate of growth declined from 45 to 20% in 24 hours. This was paralleled by a drop in 59Fe incorporation from 35 to 12% and in the reticulocyte count from 85 to 14.5%. It is concluded that the rate of erythropoiesis in fetal life is largely controlled by the rate of growth and the corresponding increase in hemoglobin mass.


Serum erythropoietin measurements using the fetal mouse liver cell culture: the importance of reduction of variation in the specific activity of radioiron--transferrin.

Because of varying iron--transferrin concentrations in different serum samples, and varying test serum portions within the culture, variations of the radioiron--transferrin/total iron--transferrin ratio are inevitable, when serum erythropoietin (Ep) concentrations are measured using the fetal mouse liver cell assay. It could be demonstrated that radioiron uptake is directly proportional to the specific activity of radioiron--transferrin, when the latter varies over the range which is inherent to the method. Variations of the ratio of radioiron--transferrin/total iron--transferrin were reduced by preincubating radioiron with human transferrin, and by minimizing the test serum portion of the culture. With this modified in vitro bioassay, serum Ep concentrations of 59 healthy subjects were measured. Mean serum Ep concentration was 136 +/- 66 (s.d.) mU/ml.


Hemoglobinemia in rats exposed to high altitude.

A hemoglobinemia occurred in rats exposed to a simulated altitude of 18,000 ft. No biochemical deficits in the erythrocytes or plasma were apparent, and the erythrocytic survival time was normal. This hypoxia-induced hemoglobinemia was not due to intravascular hemolysis and it coexisted with polycythemia, representing a unique hematologic condition. As a result of the hemoglobinemia in altitude-exposed rats, plasma haptoglobin was depleted, a 5- and 10-fold increase in the activities of heme oxygenase were induced in the liver and kidney, respectively, and there was a hemoglobinuria. The possible mechanism for the genesis of this hypoxia-induced hemoglobinemia is discussed.


Studies of erythrocyte protoporphyrin in anemic mutant mice: use of a modified hematofluorometer for the detection of heterozygotes for hemolytic disease.

Erythrocyte protoporphyrin concentration was determined on a single drop of blood from normal and anemic mutant mice using a modified hematofluorometer. Mice showed age- and sex-dependent changes in protoporphyrin concentrations. Mice with hypoplastic anemias had a slight elevation and mice with iron deficiency anemia had a moderate increase in red cell protoporphyrin. Those with inherited hemolytic anemias had a marked elevation of erythrocyte protoporphyrin. Mice heterozygous for hemolytic anemias had no overt hemolysis and reticulocytosis, yet their erythrocyte protoporphyrin concentrations were distinctly higher than their littermate controls. Previously these heterozygotes were differentiated only by laborious and expensive progeny testing. This paper is the first demonstration of a quick and practical way of detecting mice heterozygous for hemolytic anemias by erythrocyte protoporphyrin determination. The data of this study demonstrate not only the usefulness of the hematofluorometer for protoporphyrin determination in the diagnosis of mouse anemias, but also the significance of elevated erythrocyte protoporphyrin as a very sensitive indicator of increased erythropoiesis, or of iron deficiency.


The cellular blood picture of the Mongolian gerbil throughout the first year of life: a longitudinal study.

The Mongolian gerbil was subjected to a longitudinal study of its cellular blood picture throughout its first year of life. This laboratory rodent initiates its neonatal period with an erythrocytic macrocytosis, a subadult red cell count and panleukocytosis, followed by a transient leukopenia. The adult blood picture is attained by 8 weeks with an erythrocyte count of 8.5--9.0 X 10(6) rbc/mm3 and a leukocyte level of 10--12 X 10(3) cells/mm3. The erythrocytes are microcytic (approximately 53 mu3) and frequently demonstrate polychromasia as well as basophilic stippling. There is a sexual dimorphism favoring the male in the erythrocyte corpuscular volume, mean corpuscular hemoglobin, hematocrit and hemoglobin values.


Responses of group IV afferent units from skeletal muscle to stretch, contraction and chemical stimulation.

In an attempt to differentiate between nociceptive group IV muscle receptors and "ergoceptive" ones, the discharges of single group IV fibres from skeletal muscle in response to local pressure, sustained stretch, repetitive contraction and intra-arterial injections of bradykinin, 5-hydroxytryptamine (5-HT), potasssium, phosphate, and lactate were studied in anesthetized cats.


The development of vision in cats after extended periods of dark-rearing.

The time course of development of visual acuity for square wave gratings was measured behaviourally in a number of cats that were reared in total darkness until they were either 4 (5 cats) or 6 (1 cat) months of age. Less extensive measurements were also made on animals reared in a similar manner until they were either 1 1/2 or 10 months old. Initially, all the animals appeared to be blind, but signs of vision became evident after periods of time in an illuminated environment that ranged from a few days, in the case of animals dark-reared for only 1 1/2 to 4 months, to 1 to 2 months for those animals that were deprived for 6 months or more. Thereafter, visual acuity as measured on a jumping stand progressively improved, reaching, in the case of animals deprived for 4 months, values that were comparable to those of normal animals (6.9 cycles/deg) after 4 months of exposure to light. The animal deprived for 6 months remained apparently blind for a month and eventually attained an acuity (5.7 cycles/deg) that was somewhat less than that of normal animals. The fact that such high acuities can be achieved after periods of binocular deprivation that extend throughout the classically defined "critical period" suggest that the effect of dark-rearing is somehow to impede the natural decline with age in the degree to which cortical neurones are susceptible to environmental modification.


Modification of the kitten's visual cortex by exposure to spatially periodic patterns.

Kittens were dark-reared except for exposure to three types of spatially periodic, vertically striped pattern: 1. single, widely spaced black bars; 2. wide areas of regular vertical grating separated by large blank patches; 3. a uniform, continuous grating with a spatial frequency of 0.5 c/deg. In each case there was a bias towards vertical in the distribution of preferred orientations of cells recorded in the visual cortex. The contrast sensitivity of individual neurones for gratings of different spatial frequencies was analysed quantitatively. In kittens exposed to a uniform grating of 0.5 c/deg, many cells were maximally sensitive close to 0.5 c/deg, as they are in normal cats. The occipital potential evoked by vertical gratings higher in frequency than 0.3 c/deg was consistently greater in amplitude than that for horizontal, and a vertical grating of 0.5 c/deg produced the maximum activity. These results are compared with those of Maffei and Fiorentini (1974); the differences between our results and theirs may be attributable to the degree of variability in spatial frequency and orientation during rearing, and to the duration of exposure.


Hippocampal place units in the freely moving rat: why they fire where they fire.

Place units in the dorsal hippocampus of the freely-moving rat signal the animal's position in an environment (place field). In the present experiments, thirty four place units were recorded in two different environments: one, a small platform where the rat had received neither training nor reward; the other, an elevated T-maze inside a set of black curtains where the rat had been trained on a place discrimination. The places within the curtained enclosure were specified by four cues (a light, a card, a fan, and a buzzer) in addition to the food. Other cues were eliminated by rotating the maze and the four controlled cues relative to the external world from trial-to-trial. Some units had place fields in both environments while others only had a place field in one. No relationship could be seen between the place fields of units with fields in both environments. All twelve units tested extensively in the controlled enclosure had place fields related to the controlled cues. Probe experiments in which only some of the controlled cues were available showed that some of these units were being excited by one or two cues while others were influenced in a more complex way. The fields of these latter units were maintained by any two of the 4 cues and were due to inhibitory influences which suppressed the unit firing over the rest of the maze.


Ascending and intrinsic projections of the superior olivary complex in the cat.

The ascending and intrinsic projections of the superior olivary complex (SO) in the cat were investigated by injection of 3H-leucine and horseradish peroxidase (HRP) in SO and the inferior colliculus (IC), respectively. A topically arranged projection was demonstrated from the nucleus of the trapezoid body (NTB) to the ipsilateral lateral superior olivary nucleus (LSO) wiht a lesser connection in the opposite direction. The medial superior olivary nucleus (MSO) has a strictly ipsilateral projection, whilst LSO projects symmetrically through the lateral lemniscus (LL) of both sides, to end with topically arranged terminals in the ventrolateral part of the central nucleus of the inferior colliculus (CNIC). Terminal labelling found in the ventral and dorsal nuclei of LL (VNLL and DNLL) probably represents collaterals from bypassing fibres originating in MSO and LSO, respectively. These results were demonstrated by both techniques, whilst in addition the HRP method revealed an ipsilateral and contralateral projection to IC from VNLL and DNLL, respectively.


The effects of gallamine on field and dorsal root potentials produced by antidromic stimulation of motor fibres in the frog spinal cord.

The effects of gallamine on the intraspinal field potentials and the dorsal root potentials produced by antidromic stimulation of motor fibres were studied in the isolated frog spinal cord preparation. After gallamine (10-(3) M), the duration of the negative field potential produced by antidromic activation of motoneurons (N1 response) was increased often without changing its amplitude. This resulted in an increased passive spread of the antidromic action potential towards the dorsal dendritic regions, where afferent fibres terminate. In the untreated spinal cord, stimulation of motor axons produced a late negative dorsal root potential (VR-DRP) which was depressed after gallamine administration. Abolition of the VR-DRP was frequently associated with the appearance of a short latency, conducted response, in the dorsal roots (EVR-DRP). The earliest component of the EVR-DRP had a latency ranging between 0.5 and 2.5 ms measured after the peak of the N1 response recorded at the motor nucleus. Such a brief latency of the EVR-DRP suggests that this response results from electrical interaction between motoneurons and afferent fibres. After gallamine, the primary afferent depolarization produced by orthodromic stimulation of sensory nerves facilitates the EVR-DRP without necessarily increasing the amplitude or duration of the N1 response. Also, gallamine appears to increase directly the excitability of the afferent fibre terminal arborizations. The nature of the electrical interaction between motoneuron dendrites and afferent fibre terminal arborizations is discussed in terms of two hypotheses: interaction by current flows and by electrical coupling.


Effect of metergoline on delayed response in cats and its relation to the metabolism of dopamine and serotonin in neostriatal and mesolimbic neurons.

In cats the effect of Metergoline (Liserdol, Farmitalia) was investigated on the performance of a delayed response task and was related to the associated changes in the concentrations of dopamine, nonadrenaline and serotonin in the brain. Metergoline (14 microgram/kg/day, i.m.) administered during the first 10 days of the training significantly decreased response latencies at delay periods of 0, 3, 9 and 27 sec without significantly affecting the number of errors. Biochemical assays showed that the improved performance correlated with the increased dopamine content of limbic structures and the decreased serotonin content in all brain structures. The concentrations of dopamine in the neostriatum remain unchanged. Response latencies and the number of errors in cats treated with Metergoline were significantly different from those in animals treated with L-DOPA (30 mg/kg/day) probably relfecting the specific biochemical disturbance induced by the two drugs. These results suggest an inhibitory influence of serotoninergic pathways on areas like the meso-limbic system retaining high concentrations of dopamine.


Pontomedullary reticular projections into the region of the ascending medial longitudinal fasciculus in cat.

The medial longitudinal fasciculus (MLF) and immediately adjacent reticular formation were stimulated electrically just caudal to the trochlear nucleus in the cat. In the pontomedullary reticular formation within 1.5 mm of the midline, antidromically excited neurons were detected in (1) the contralateral abducens nucleus, (2) the contralateral reticular formation just caudal and caudoventral to the abducens nucleus, and (3) the ipsilateral nucleus reticularis pontis caudalis beneath and rostral to the abducens nucleus. The possible involvement of these neurons in eye or body movements is discussed.


Statistical dependence between neighboring retinal ganglion cells in goldfish.

Simultaneous recordings were made of the spontaneous discharge of neighboring retinal ganglion cells in goldfish. Crosscorrelation analysis indicates two types of correlation. Neighboring units with like receptive field organization tend to discharge together while units having complementary receptive field organization tend not to discharge together.


Spinal mechanisms of the functional stretch reflex.

A sudden and rapid angular displacement of the limb evokes, in human and monkey subjects, a segmented pattern of electromyographic activity in muscles which are stretched. While the first segment is acknowledged to represent a tendon jerk, it has been proposed that the second segment, occurring with a shorter latency than a reaction time, is mediated by a transcortical loop. The present experiments were conducted in cats to determine the properties of muscle responses to torque perturbations analogous to those used in the monkey, and to determine if the integrity of supraspinal pathways is required for the individual response segments to occur. Torque perturbations which flexed the forearm evoked a segmented response in the electromyogram of the cat triceps muscle. This response typically consisted of three early segments with latencies of 10, 30 and 60 msec which were similar to the M1, M2, and M3 segments described in the monkey. The M3 and occasionally M2 components were depressed when the cat followed rather than resisted the perturbation. A torque pulse of 10 msec duration was sufficient to elicit a near maximal M1 response while torque pulses in excess of 20 msec were required to evoke the M2 response. To determine if any of these components required mediation by the cerebral cortex, experiments were conducted in decerebrate and spinal cats. Similar torque perturbations produced segmented electromyographic responses in the triceps muscles which were indistinguishable in their timing from those observed in intact cats. The torque required to produce the segmented responses was comparable as well. All three segments were dependent upon the activation of receptors in the homonymous muscle and did not require cutaneous input. These observations show that receptor properties and/or spinal mechanisms involved in the stretch reflex are sufficient to produce a segmented response similar to that observed in intact animals.


Self-innervation of dendrites in the rat suprachiasmatic nucleus.

Golgi-Cox impregnantions of the  rat suprachiasmatic nucleus show small dendritic side branches which appear to contact their neurons of origin. Electronmicroscopically a dendrite has been found forming a Gray-type-II synapse with one of its own branches. The arrangement is discussed as a general phenomenon of a feedback connection for temporal limitation of local excitation.


A new vestibular thalamic area: electrophysiological study of the thalamic reticular nucleus and of the ventral lateral geniculate complex of the cat.

Single unit recordings were carried out in the reticularis thalamic nucleus (RT) and the ventral lateral geniculate body (LGv) of chronically prepared alert cats under sinusoidal vestibular stimulation in the horizontal plane. Optokinetic stimulation was also used. Of the 57 recorded neurons, 12 present vestibular modulation in the dark, analogous to Duensing's and Schaefer's (1958) type I response in the vestibular nuclei. Responses of 26 cells are similar to response of type II vestibular neurons and 14 units have a type III response; the 5 remaining cells were activated by vestibular stimulation in the vertical sagittal plane. The majority of these cells does not present detectable direct visual responses, but 50% can be driven by optokinetic stimulation. 74% of types I, II and III neurons show saccadic resonses to vestibular nystagmic saccades in the dark. About 60% present similar saccadic modulations during optokinetic nystagmus and 55% keep this response for spontaneous saccades in the dark or in front of a striped background. The saccadic responses are constant for a given neuron in all cases of stimulation with latencies ranging from 30 msec prior to the beginning of the saccade to 120 msec after its onset. The histological localization of these units falls on one hand into the caudal part of the RT nucleus (type III neurons) above the dorsal lateral geniculate nucleus and on the other hand within the internal subdivision of the LGv and its rostral limit (all other types). The significance of this new, saccadic and vestibular focus in the feline thalamus is discussed in relation with the two previously known vestibular thalamic relays in terms of interrelations between the vestibular and the visual systems.


Studies on plasma fibrinogen level in pre-eclampsia and eclampsia.

The plasma fibrinogen level of maternal blood has been estimated in 30 cases of pre-eclampsia, 60 cases of eclampsia and 35 cases of normal pregnancy of 3rd trimester. The plasma fibrinogen value increased by about 70% and 145% in pre-eclampsia and eclampsia, respectively. In essential hypertension, the fibrinogen level remains more or less the same as in normal pregnancy.


Multiple forms of human kidney mutarotase.

4 forms of mutarotase from human kidney were demonstrated by DEAE-cellulose column chromatography. A major form of them was purified to homogeneity.


Effect of sucrose on lipogenesis of rats chronically treated with ethanol.

The effect of chronic ethanol administration with and without sucrose on the lipogenic enzymes of liver and adipose tissue of rats was studied. Ethanol markedly influenced the adipose lipogenic enzymes at 28 days. Sucrose caused a 2-10fold increase in lipogenic enzymes of both adipose and liver.


Effect of cortisone or triiodothyronine administration to pregnant rats on lysosomal hydrolases in fetal forebrain and cerebellum.

Triiodothyronine injected daily to pregnant rats for the last week of gestation (50 microgram/100 g b.wt) increased the specific activities of 5 acid glycosidases in the fetal forebrain and cerebellum. Cortisone (50 mg/100 g b.wt) administered in the same period had no effect on cerebellum acid hydrolases, but decreased their activity in the forebrain.


Enzymatic synthesis of trisialoganglioside by particulate fractions of rat liver.

Rat liver contains a particulate (membrane-bound) glycosyl transferase, concentrated in Golgi apparatus fractions, which catalyzes the synthesis of a trisialoganglioside from the ganglioside precursor disialohematoside (GD3). Sialic acid was not incorporated into exogenous GD1a from CMP-N-acetylneuraminic acid suggesting that GD1a is an endproduct of the monosialoganglioside pathway. Thus, the disialoganglioside pathway may be a primary source of trisialoganglioside and higher ganglioside homologs in adult rat liver.


Is attenuation of tRNA charging responsible for the inhibition of protein labelling accompanying depolarisation of the cerebral cortical cells?

Topical application of concentrated solutions of KCl resulted in reduction of charging of tRNA 7 min after s.c. injection of L-(U-14C) leucine. Neither radioactivity nor pool size of the total amino acids changed during this period.


Metal binding to myosin and to myosin DTNB-light chain.

The effects of various divalent cations, Ca2+, Mg2+ and Mn2+ on the intrinsic fluorescence of heavy meromyosin (HMM) and myosin 5,5'-dithio-bis-(2-nitrobenzoate) DTNB-light chain of rabbit striated muscle, are compared. At pH 6.4, th fluorescence change induced by the metal ions is present only in the isolated light chain and disappears in HMM, thus indicating an interaction between the heavy and light chains with respect to the binding of the metal ions. Whereas Mg2+ binds more strongly than Ca2+ to myosin, this order is reversed in the case of the DTNB-light chain.


Depression by ethionine of phosphorylating oxidation in hepatic mitochondria.

Induction of hepatic steatosis and suppression of hepatic ATP levels, protein synthesis and gluconeogenesis subsequent to administration of ethionine may be consequences of interference by this compound with mitochondrial phosphorylation of ADP. The mitochondrial dysfunction is not a direct action of ethionine on the organelle.


Effect of relative humidity on the free-living stages of Strongyloides papillosus (Rhabdiasoidea: Nematoda).

The eggs and larvae are affected by the changes in the humidity level around them. The eggs do not develop below 87% relative humidity at 30 degrees C and 25 degrees C. At sub-developmental rel. hum. they remain viable for 30 h at 81%, but at 73% rel. hum. level they do not survive beyond 18 h. Survival of larvae in 100% rel. hum. is longer at 30 degrees C than at 25 degrees C and 35 degrees C, and also they exhibit a poor resistance to desiccation.


Labeling of endotoxin lipopolysaccharide with technetium-99m pertechnetate.

Bacterial endotoxin treated with technetium-99m can be visualized in living animals by gamma camera imaging.


Activity of the reticuloendothelial system following exposure to electric stress and thymectomy.

After electric stress stimulation, granulopectic activity is reduced in otherwise normal rats, whereas it appears to be increased in thymectomized animals. The differences between the 2 groups of animals seem to support the hypothesis that the effects of stress upon the overall phagocytic capacity may be mediated by the products of lymphocyte breakdown.


Cocci and diphtheroids in blood cultures from patients in various pathological situations.

The evolution of cocci and diphtheroids taking origin from cell-wall-deficient forms seems not to be related to a particular state of illness, but to be the consequence of a generalized crypto-infection.


Intracellular behaviour of Leishmania enriettii within murine macrophages.

Both promastigotes and amastigotes of Leishmania enriettii were readily ingested by mouse peritoneal macrophages (MPM). Promastigotes after their entry within MPM were rapidly immobilized and their multiplication was never observed. Microscopic examination revealed that ingested promastigotes were degraded with MPM. Nonmotile amastigotes of L. enriettii taken up by MPM, on the other hand, multiplied intracellularly and eventually destroyed the infected cells.


Metabolic studies of Hg-203 on Chlamydomonas reinhardi.

Sterile cultures of Chlamydomonas reinhardi, WT+, were treated with Hg-203 at 25 degrees C to identify probably formed volatile mercury compounds. Experiments were performed with living and dead cells under aerobic or anaerobic conditions, respectively, and the mercury concentration was measured in the system algae/nutrient medium. We found a timerelated decrease of mercury concentration in the cell suspension and the cell-free nutrient medium due to a reduction of Hg++ to Hg0, probably caused by extracellular enzymes; monomethyl or dimethyl mercury could not be detected.


Do beta adrenergic agents directly stimulate gastrin secretion?

Isoproterenol if given during methacholine stimulation in dogs neither depresses gastric secretion nor elevates serum gastrin. Therefore, we conclude that beta adrenergics (isoproterenol) are unlikely to be direct liberators of gastrin, but raise serum gastrin indirectly only if they inhibit gastric secretion.


Profound hypothermia in golden hamsters (Mesocricetus auratus) induced by serotonergic potentiating and noradrenergic inhibiting drugs.

Profound hypothermia (6 degrees C) was induced in cold exposed golden hamsters (Mesocricetus auratus) by a combination of drugs that potentiate brain serotonergic activity (fluoxetine and pargyline) and inhibit noradrenergic activity (alpha-methyl-p-tyrosine). Individual drugs and combinations of 2 were ineffective.


Demilune cells of the cat submandibular gland; an unlikely source of kallikrein.

The functional significance of kallikrein in the salivary gland remains unclear partially because of uncertainty over its precise cellular localization. Kallikrein was thought to originate in acinar cells, until recent evidence from cat and rat localized it primarily to the ducts. The possibility that salivary kallikrein may also be located in demilune cells was investigated in this study. - The total kallikrein content of cat submandibular glands was found to be substantially reduced by sampathetic nerve stimulation; whereas parasympathetic stimulation had no significant effect. These biochemical findings did not correlate with morphological studies that revealed almost complete depletion of the demilune cells secretory granules after stimulation of either division of the autonomic nerve supply. This lack of correlation makes it unlikely that kallikrein is present in the demilune cell secretory granules.


Change in taste preference related to aging of taste cells in rat.

Following the suppression of renewal of rat taste cells by vinblastine sulphate, the preference for sucrose decreased markedly while the aversion to quinine did not change. The results suggest that the sensitivity of taste cells to sucrose decreases with their aging, but the sensitivity to quinine increases.


Frequency gradient in the autorhythmicity of the pyeloureteral pacemaker system.

The pacemaker properties of the various regions of isolated segments of the rabbit renal pelvis were examined. The results show that pacemaker frequency and waveform of contraction change significantly within the renal pelvis. The highest frequency was encountered at the fornix, while the ureteropelvic junction is lowest.


Asymmetry of turning behaviour of rats induced by amphetamine and apomorphine.

Turning behaviour of rats following injection of amphetamine is in the same direction as following apomorphine. Unilateral common carotid artery ligation does not affect this asymmetry. Thus the reason for the asymmetry in turning behaviour following injection of amphetamine is probably due to postsynaptic dopaminergic asymmetry within the corpus striatum.


The effect of bradykinin on the electrical activity of rat jejunum.

Bradykinin increased the potential difference across both the jejunum and colon of the rat. This effect was significantly reduced by indomethacin, suggesting that it was mediated by prostaglandins. The possibility that bradykinin may contribute to the diarrhoea of the carcinoid syndrome by inducing a net secretory state in the intestine is discussed.


Electrogenic hyperpolarization in canine cardiac Purkinje fibres exposed to calcium ionophores.

The Ca ionophores markedly enhance the increase of intracellular Ca occurring during Na-free perfusion and the hyperpolarization observed upon Na readmission may be due to rapid restoration of intracellular Na and resultant stimulation of both electrogenic sodium and calcium efflux.


Localization of renal kallikrein in the dog.

Renal kallikrein was estimated in glomerular, tubular and medullary fractions of dog kidneys. It was found primarily in the cortex, the highest level of activity being detected in glomeruli-rich fraction. These results support previous observation that kallikrein may be associated with the juxta-glomerular complex.


Influence of age on the renal renin response to a high salt intake in the rat.

Saline drinking combined with DOCA-treatment was found to decrease renal renin in weanlings at a higher rate than in adult rats, with a comparable saline consumption level. The decrease was not potentiated by uninephrectomy.


Effect of sex hormones on plasma cholesterol in castrated and noncastrated male rats.

The administration of estradiol to both castrated and noncastrated male rats was associated with significantly increased plasma cholesterol levels as compared to controls, the estradiol in the noncastrated rats overriding the tendency of testosterone to lower plasma cholesterol.


Gastrin stimulated H+ secretion in amphibian gastric mucosa: effect of tetrodotoxin.

The role of neural mechanisms in gastrin stimulated H+ secretion was studied using amphibian gastric fundic mucosa. Spontaneously secreting mucosae were converted to resting state (zero H+ secretory rate) using Burimamide. Following removal of burimamide, 3 X 10(-6) M tetrodotoxin did not block gastrin stimulation of H+ secretion indicating that neural mechanisms are not required.


Influence of phenylbutazone on bile flow in the rat.

Phenylbutazone, a well-known enzyme inducer, at a dose of 80 mg . kg-1 once daily for 8 days increases liver weight and bile flow expressed per g of liver (p less than 0.01). The bile salt secretory rate is not increased.


Interaction between delta-6-tetrahydrocannabinol (delta-6-THC) and lithium at the blood brain barrier in rats.

Neither the acute nor the chronic i.p. administration of delta-6-tetrahydrocannabinol affected the passage of lithium from blood to brain in normal rats.


Inhibition of the efflux of organic ions from renal cortical slices.

Cyanine 863 inhibited the efflux of tetraethylammonium ion from slices of rat or rabbit renal cortex while the efflux of p-aminohippuric acid was unaffected. Dinitrophenol increased the efflux rate of both the cation and anion. Cyanine also decreased the dinitrophenol-enhanced efflux of tetraethylammonium (TEA).


Are anticholinergic effects responsible for the heterogeneous quinidine-induced modifications of heart muscle refractoriness?

Vagal tone is responsible for the heterogeneous reactivity of atrial and ventricular contractile tissues to quinidine. Acetylcholine may make atrial cells more sensitive to the effects of quinidine.


The inhibitory effects of a dermal extract upon granulation tissue.

Injection of a water-soluble dermal extract into adult rats resulted in depression of DNA synthesis in granulation tissue at 3 different sites of injury, but not in epithelium. This suggests that connective tissue proliferation may be controlled in part by a chalone-like mechanism.


Inhibition of reserpine-induced PGO waves in the cat by ergot derivatives.

The number of reserpine-induced PGO waves in the cat is decreased by administration of ergot derivatives. The inhibition is dose-dependent and the various ergot derivatives show differing potencies. The action of the ergot derivatives may result from stimulation of central serotonin receptors. In addition, possible involvement of dopaminergic systems is discussed.


Cytostatic activity of organic compounds and their average quasi-valence number.

It is found that the average quasi-valence numbers of alkylating cytostatics lie in the region of potential carcinogens, while the average quasi-valence numbers of antimetabolites predominantly cover the region of noncarcinogens. Implications of this finding on the design of new drugs are discussed.


Effect of variations in temperature on antimuscarinic activity in guinea-pig atria.

The characteristics of the antimuscarinic activity of homatropine, gallamine and stercuronium in guinea-pig atria remained constant over the temperature range 22--37 degrees C in that a linear Arunlakshana-Schild plot was obtained with homatropine and nonlinear plots occurred with gallamine or stercuronium. A trend towards higher dose-ratios with reduction in temperature was only significant for gallamine.


Gastric cancer in rats after chronic intraperitoneal application of sap of green parts of potatoes (Solanum tuberosum L.).

Chronic i.p. application of the sap of green potato plants (potato-tops) induced carcinomas of the stomach in 4 out of 12 treated rats.


Are intermediate filaments of vertebrate smooth muscle cells and tonofilaments of epithelial cells identical cell structures?

In epithelial and smooth muscle cells of the urinary bladder of the frog, a class of filaments exists which is partly disintegrated by glycerol treatment and very resistant to potassium solutions of high ionic strength.


Involutive morphological modifications in the rat adrenal glomerular zone after a low-sodium diet.

We have studied glomerular zone involution in the rat's adrenal gland after a period of hyperfunction brought about by a low-sodium diet. The changes observed in this zone effect those organoids that are more directly involved in steroid genesis; mitochondria, smooth endoplasmic reticulum and liposomes. The Golgi complexes appear very developed, often, showing, a positive acid phosphatase activity. Lysosomes suffered a considerable increase in their number, and carried out their digestive function on liposomes. All those changes discussed here are seen as an accomodation of this zone to the new normofunctional situation.


Types of nerve terminals in fetal and neonatal rabbit myocardium.

With the use of electron microscopy 4 types of axonal profiles were observed in the developing myocardium of rabbits: 1) adrenergic axons which contained mainly small dense-core vesicles and which presumably can store 5-hydroxy-dopamine; 2) cholinergic axons which contained small clear synaptic vesicles and which were acetylcholinesterase-positive; 3) axons which contained large vesicles filled with moderately electron-dense material and which resembled purinergic axons; and 4) profiles filled with mitochondria, vesicles of various sizes, lysosome-like bodies, and microtubules and which resembled sensory terminals.


Presence of oncornavirus-like particles in the P388 murine leukemic cell line.

A culture of P388 murine lymphoblastoid cells has been shown to contain type C oncornavirus-like particles budding at the plasma membrane. Occasionally intracytoplasmic type A and immature type B particles were also observed by electron microscope techniques. The discovery of oncornavirus-like particles in the P388 cell line increases the utility of this neoplastic system for detecting potential antineoplastic agents.


Fluorescence microscopical study of 5-hydroxytryptamine storage organelles in mepacrine-incubated blood platelets of beige mice (Chediak-Higashi syndrome).

The number and fluorescence intensity of fluorescent granules (5-HT storage organelles) of mepacrine-incubated blood platelets of beige mice (Chediak-Higashi syndrome) are decreased compared to those of control mice platelets. This indicates both quantitative and qualitative changes of the 5-HT organelles, namely a reduced number and a reduced storage capacity, respectively.


Cortisol-induced migration of eosinophil leukocytes to lymphoid organs.

Cortisol induces a migration of eosinophil leukocytes from the blood to several lymphoid organs, such as the spleen, lymph nodes and thymus, but not to other tissues. This migration explains the cortisol-induced blood eosinopenia, which is much more pronounced in intact than in splenectomized animals.


HLA BW54 and B5 in Japanese diabetics with juvenile-onset and insulin-dependency (with special reference to the family history).

The frequency of HLA BW54 and B5 in Japanese patients with JOD is increased and decreased, respectively. In JOD patients without a family history of MOD, the frequency of BW54 is significantly increased, whereas in JOD patients with a positive family history the frequency was not increased in a statistically significant manner.


Effects of oestrogen and progesterone on rat pineal N-acetyl transferase activity and melatonin production.

We have extended previous studies on pineal beta-receptors to include effects of oestradiol or PMSG treatment in the immature female rat. Neither manipulation has any effect on norepinephrine-induced N-acetyl transferase (NAT) activity in vitro. In the adult ovariectomised rat oestrogen/progesterone priming exerts a small sensitising effect to beta-stimulation with isoproterenol. Progesterone alone, in vitro, inhibits the release of melatonin from pineals of adult ovariectomised rats.


An improved method for estimating the activity of a mouse with the photoswitch.

A new method for estimating the activity of a mouse by means of the photoswitch is contrived. This device can follow the activity with high fidelity and notable sensitivity, as compared with the conventional method.


Infusion at constant rate in vivo.

Infusion can be maintained at a constant rate over an extended period of time in vivo by the use of an implanted diffusion chamber. Plasma 59Fe was maintained at a constant level for 10 days when infused from a s.c. implant. Injected isotope was cleared exponentially with a half-clearance time of about 8 h.


A simple technique for the measurement of 3H- and 14C-radioactivity per microgram DNA in fixed tissue.

A simple, rapid and versatile technique for scintillation counting of double labelled fixed tissue is described. Furthermore, DNA determination can be performed on the same tissue digest.


Cocarcinogens of the diterpene ester type from Croton flavens L. and esophageal cancer in Curaçao.

From the roots of Croton flavens L., 3 highly irritant and tumor promoting Croton factors F1--F3 and the corresponding 3 cryptic Croton factors F'1--F'3 were isolated and characterized as novel esters of 16-hydroxy- and 4-deoxy-16-hydroxyphorbol, respectively. These findings suggest that tumor promoters of the phorbol ester type, ingested through the widespread and frequent use of Croton flavens according to local habits, may be causally related to the well recognized high rate of esophageal cancer on Curaçao.


On the solvent-extraction of acetylcholine receptor.

Chloroform/methanol rechromatography on Sephadex LH-20 of fractions isolated from organic solvent extracts of E. electricus electric organs exhibited alterations in elution point compared to the original chromatography. Additionally, 3H decamethonium bromide did not coelute with any of the observed fractions. It is concluded that as presently described the organic solvent isolation procedure for the cholinergic receptor exhibits undesirable characteristics.


Induction of epidermal cell proliferation by a tumour promoter in vitamin B6-deficient mice.

Topical application of the tumour promoter 12-0-tetradecanoyl-phorbol-13-acetate to skin caused a marked enhancement of mitotic activity both in mice maintained on a complete diet or on a vitamin B6-deficient diet.


Activation and specificity of alkaline phosphatase of a mineralizing collagen-rich system.

Alkaline phosphatase from tibia tendon of Meleagris gallopavo L. was highly purified. The enzyme activation by different ions was measured. Mg2+ showed a high activation with a broader spectrum of phosphomonoester hydrolization. The in vivo Mg2+ concentration was an optimum for in vitro activation.


Glycosaminoglycans in separated tubules of the guinea-pig and rat kidney medulla.

Isolated tubules of the renal medulla of guinea-pig and rat contained glycosaminoglycans. 20--25% of the uronic acids corresponded to hyaluronic acid. In the guinea-pig, chondroitin and dermatan-sulfates accounted for at least 50% of the uronic acids, whereas, in the rat, heparan sulfates comprised 65--70% of them.


The metabolism of dibenz[b,f]-1,4-oxazepine (CR): in vivo hydroxylation of 10,11-dihydrodibenz[b,f]-1,4-oxazepin-11-(1OH)-one and the NIH shift.

Studies of the in vivo metabolism of 10,11-dihydrodibenz[b,f]-1,4-oxazepin-11-(1OH)-one (2) specifically deuteriated at C7 implicate an arene oxide intermediate during the conversion to 7-hydroxy-2 (4) as evidenced by the observation of the NIH shift.


Time-qualified reference intervals - chronodesms.

Methods are presented for qualifying clinical reference intervals, for individuals as well as peer groups, according to circadian and other rhythms, using chronobiologically-defined single samples or time series.


Differential scanning calorimetry of rat liver mitochondria.

Differential scanning calorimetry was employed for studying rat liver mitochondria and extracted mitochondrial lipids. Endothermic transition in the range 15--40 degrees C was detected for the whole mitochondria and between 10--20 degrees C for the extracted lipids.


The site of 25-hydroxycholecalciferol stimulated protein synthesis in the rat kidney.

Autoradiographs of the kidneys of rachitic rats dosed in vivo with 250 pmoles 25-hydroxycholecaliferol (25-OHD3) and 3H-leucine showed increased grain counts in portions of proximal renal tubules. On incubation of kidney slices the synthesis of only 1 cytosol protein was found to be stimulated by the steroid. On disc gel electrophoresis it had the characteristics of renal calcium binding protein.


Agglutination of erythrocytes using lectin-labeled spacers.

The mechanism of agglutination of human erythrocytes by lectin, studied using lectin-labeled gold granules as spacers (5--64 nm in size), was found to depend upon the size of the spacer but not upon the number and the mobility of the receptors.


Effect of albendazole on the metacestodes of Taenia saginata in calves.

Albendazole, a benzimadazole-carbamate anthelmintic, has been shown to effectively cause destruction of the metacestodes of Taenia saginata in calves.


The level of action of 2,4-D on transcription.

In mature cells, 2,4-D retards transcription when it is applied before 3H-uridine incorporation. But transcription is accelerated when it is applied after feeding with 3H-uridine. It has been suggested that the action of 2,4-D on transcription is only at the level of initiation.


Damage by ozone to the mechanical integrity of the protoplast plasmalemma.

Ozone acts on the plasmalemma as to weaken its mechanical properties. This results in the bursting of protoplasts.


Anthelmintic activity of tioxidazole (Sch 21480) against gastrointestinal roundworms.

Methyl-6-propoxybenzothiazole-2-carbamate (tioxidazole) has broad spectrum activity against gastrointestinal nematodes.


On the residual water content of dried but viable cells.

We have examined the residual water in dried cysts of the brine shrimp, Artemia salina, by gas-bombardment techniques at reduced pressures and temperatures. This treatment reduced, but did not remove all the residual water, the lower limit being about 0.0069 gH2O/g dried weight. The significance of such small amounts of water to cell hydration is assessed. The treatment did not appreciably reduce the viability of this cyst population.


Relationship between regeneration of cell surface glycoproteins in trypsin-treated chick embryo fibroblasts and cell adhesion to the substratum.

The ability of cells to adhere to a substratum was altered by treatment with trypsin but was restored after a 1.5-h culture. A concomitant incorporation of [3H] leucine and [14C] glucosamine in the trypsin-sensitive cell surface glycoproteins was observed and almost reached a plateau within 1.50 h following the treatment with trypsin.


A radioenzymatic method to measure picogram amounts of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) in small samples of brain tissue.

A radioenzymatic method for simultaneous determination of dopamine and DOPAC in small brain areas is described. By using this assay, 250 pg of dopamine and 150 pg of DOPAC can be estimated. The present method has been applied to compare the effect of different psychotropic drugs on the dopamine and DOPAC levels in the caudate nucleus, substantia nigra and medial basal hypothalamus.


Sex difference in polyethylenglycol-induced thirst.

The polyethylenglycol-induced thirst in male and female castrated rats has been studied. The polyethylenglycol (PG) increases the water intake more in females than in males. Estradiol benzoate and testosterone P. diminishes the amount of water drunk after PG treatment in the females, but not in the males.


Bayliss myogenic response in the isolated ductus arteriosus of guinea-pig and rabbit fetuses.

Isolated ductus arteriosus responds by marked constriction to increases in perfusion pressure. If, however, these increases exceed 90 mm Hg-130 mm Hg, the vessel suddenly dilates and its responsiveness becomes depressed. The importance of these findings in postnatal closure of ductus arteriosus is discussed.


Distribution of radioactivity after administration of 3H-5-hydroxytryptamine by three different routes to the mussel Mytilus edulis.

Intracardiac injection gives proportionately higher and earlier peak concentration in tissues that specifically accumulates it, i.m. injection gives slower but longer lasting accumulations, and topical application to a ganglia essentially localizes the drug in that structure.


Changes in cholinesterase activity of muscle after crushing the sciatic nerve of rats.

The subcellular distribution of cholinesterase (ChE) was studied in the gastrocnemius muscle of rats after strong or weak nerve crushing. The ChE activities of muscle were decreased to a greater extent by strong crushing than by weak crushing. In particular, the ChE activity of the fraction containing sarcoplasmic reticulum was most greatly decreased. These results suggest that the change in the ChE activity of the microsomal fraction most finely reflects the strength of nerve crushing.


Effects of brain monoamine depletion on thermoregulation, active avoidance, and food and water intake in rats.

Intraventricular administration of 6-OHDA or 5,6-DHT suppressed food intake, whereas their effect on active avoidance produced a suppression with the former and an enhancement with the latter. The increased water intake was specifically associated with 5,6-DHT treatment in rats.


Acetylcholinesterase decrease in the optic lobe after unilateral eye deprivation.

Unilateral eye enucleation in a teleost and a turtle results in progressive AChE decrease in the optic lobe controlateral to the extirpated eye. The final difference reaches 15% in teleost and more than 20% in turtle. No drastic differences in localization, but a rearrangement of histochemical pattern, due to the degeneration of retinal fibres, is noticed.


Specific in vivo binding of d-LSD in rat brain.

A reproducible in vivo d-LSD binding method in rat brain is described, with high affinity (Kd of 5 pmoles/g wet wt), stereospecificity (d- vs. 1-LSD) and regional selectivity. It may be a useful adjunct to in vitro methods for measuring changes in turnover at the synaptic level related to the intact receptor.


Bacillus thuringiensis delta-endotoxin: evidence that toxin acts at the surface of susceptible cells.

Enzymically activated delta-endotoxin of Bacillus thuringiensis covalently bound to Sephadex beads, has the same effect on insect cells in tissue culture as free toxin. The effect is prevented by antitoxin antibody and heat denaturation and is not due to a nonspecific protein effect, the beads, or toxin released from the beads. The toxin, therefore, probably acts at the cell surface.


Irreversible depigmentation of dark mouse hair by T-2 toxin (a metabolite of Fusarium sporotrichioides) and by calcium pantothenate.

T-2 toxin, a trichothecene metabolite of several Fusarium spp. causes depigmentation of dark mouse hair at the site of its application. Calcium pantothenate, though usually considered as antigreying factor, caused depigmentation at the site of its i.p. injections, at high concentration.


Effect of food and light schedule on bile flow in the rat.

In the rat after food intake, whether during the dark or light period, bile flow increases. Food intake seems to be a major factor in the circadian rhythm of bile secretion.


The influence of a new antitumor agent on hemopoietic colony forming cells.

The cytostatic and immunsuppressive agent N'-methyl-N'-beta-chloroethylbenzaldehyde hydrazone (B1) in in-vitro experiments has a stimulating effect on colony-forming culture (CFUc) of bone marrow from C57BL mice. This unusual behaviour, which is in contrast to other cytostatics, could also be observed in vitro with CFUc obtained from mice treated with therapeutic doses of B1 for 2 weeks. This stimulation is not a particular effect of B1 alone but seems to depend on a synergistic effect of the combination of B1 and the colony-stimulating activity (CSA) present in the serum from endotoxin-treated mice (MP) in the testing system. The results suggest that the described effect of B1 is due to an interference at the cell membrane of CFUc or their precursor cells.


Reconsideration of a test for dopaminergic stimulation: inability of apomorphine to induce mouse jumping.

Apomorphine was administered parenterally to mice in an unsuccessful attempt to induce amphetamine and L-3,4-dihydroxyphenylalanine-like elicited jumping. The efficacy of jumping behavior as an indicator of dopaminergic overstimulation is criticized in light of the results.


Retrograde lymphatic spread of colonic carcinoma to the liver.

Retrograde lymphatic permeation of the liver by a malignant neoplasm is an unusual phenomenon and has apparently not been reported with colonic carcinoma. This paper presents such a case: the features of the lesion are similar to those described for other primary sites.


Interaction of cocaine and bunaphtide on the 3H-norepinephrine uptake mechanism on isolated left atrium of guinea-pig.

Bunaphtide induces a blockade in the 3H-norepinephrine uptake and retention in the isolated guinea-pig left atrium. However, this blockade does not seem to be related with the cardiodepressant effect of the drug.


Effects of anaesthesia and chronic catheterization on circulating levels of prostaglandins (PGE2 and PGF2alpha in dogs.

Chronic catheterization of aorta and inferior vena cava in dogs did not significantly affect circulating levels of prostaglandins (PGE2 and PGF2alpha). Pentobarbital (30 mg/kg i.v.) anaesthesia produced a significant decrease in PGF2alpha.


Lipid accumulation in mouse hepatocytes after morphine exposure.

After morphine injection lipid accumulation in mouse hepatocytes begins within 2 h and continues for 24 h when most hepatocytes are filled with lipid droplets. In spite of morphine maintenance the liver recovers as the accumulated lipids are coupled with protein and subsequently transported and released into the perisinusoidal space of Disse.


Mechanisms of lipid peroxidation: iron catalyzed decomposition of fatty acid hydroperoxides as the basis of hydrocarbon evolution in vivo.

Ethane and pentane are evolved during peroxidation of tissue lipids in vivo and are believed to be derived from omega3 and omega6 fatty acids respectively. We present evidence supporting a scission mechanism as the means of forming these hydrocarbons during hydroperoxide decomposition. A fatty acid omega6 hydroperoxide (methyl 13-hydroperoxy-6,9,11-octatrienoate), when incubated with a ferrous ion, yielded pentane as the major hydrocarbon (98%). Reaction with ferrous ion results in an alkoxy capable of undergoing scission to an aldehydic fatty acid and a hydrocarbon.


Genetic basis of susceptibility for development of neoplasms following treatment with N-methyl-N-nitrosourea (MNU) or x-rays in the platyfish/swordtail system.

Specific genotypes of the xiphophorine fish develop neoplasms following treatment with N-methyl-N-nitrosourea or X-rays. Several of these neoplasms can be related to the presence of specific chromosomes. The implication of these findings are discussed.


Effect of vagotomy upon the neurohistochemical and ultrastructural integrity of the integrity of the inbuilt intrinsic nervous apparatus of the choledocho-duodenal junction.

The neurons of the choledocho-duodenal junction of the cat were shown to be neurohistochemically and morphologically independent of their extrinsic vagal connections. The effect of vagotomies upon the intrinsic nerve nets was also quite negligible.


Effect of prostaglandins on skin tumorigenesis.

Concomitant administration of prostaglandins E2 (PGE2) and F2alpha (PGF2alpha) with a carcinogen, 3-methylcholanthrene (MCA) to mice for 2 months markedly enhanced the occurrence of squamous cell carcinomas. Only epidermal cell hyperplasia occurred in mice treated with MCA alone by that time. Radioactivity measurements and electron microscopic autoradiography revealed that prostaglandins stimulate DNA, RNA and protein synthesis in neoplastic cells. These findings indicate that PGE2 and PGF2alpha can act as cocarcinogens on skin tumorigenesis.


Vesicular inclusions in the nuclei of epithelial cells of Malpighian tubes of the hemipteran, Panstrongylus megistus.

Vesicular inclusions observed in Malpighian tubes of hemipterans have been associated with a virus-like infection rather than a lysosomal-type activity, which is the case of the identical cytoplasmic structures.


Long-term depression of two primary immune responses induced by a single dose of 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC).

2 primary immune responses (anti-SRBC antibody response and allograft rejection) have been tested in mice at various time intervals after single doses of either DTIC or cyclophosphamide. The DTIC-induced immunodepression proved to be extremely long-lasting, being still detectable after 2 months.


Inhibition of glycolysis by L-sorbose in dog erythrocytes.

We have demonstrated previously that in vitro L-sorbose acts directly on dog erythrocytes to induce hemolysis. Here we report that L-sorbose depresses lactate formation in dog hemolysates from glucose, mannose and fructose but not from glucose-6-phosphate and galactose, suggesting that L-sorbose interacts with glycolysis at the level of the hexokinase.


A new antisickling agent: in vitro studies of its effect on S/S erythrocytes and on hemoglobin S.

2-(benzoylamino) pyridinium benzoate (BAPB) has exhibited an antisickling effect with homozygous S/S erythrocytes in vitro. This study suggests that BAPB prevents sickling by inhibiting the gelation of hemoglobin S.


The acidic glycosaminoglycans in gasric mucosa of athyroid rats: The effects of L-tri-iododthyronine.

Hyaluronic acid is increased about 12%, whereas dermatan sulfate is decreased about 34%, in gastric mucosa of athyroid rats when compared with controls. Administration of 2 doses of L-tri-iodothyronine reversed the effects of thyroidectomy.


Plasma motilin levels in duodenal ulcer and effect of a truncal vagotomy and hypoglycaemia.

The identical response of plasma motilin levels, in duodenal ulcer patients and healthy controls, to a test meal and insulin induced hypoglycaemia, fail to demonstrate any significant abnormalities in motilin release. The close correlation between blood glucose and motilin suggest a possible role of this new hormone in carbohydrate metabolism.


The effect of methallibure (I.C.I. 33,828) on the steriodogenesis in the ovary and testis of a fresh water teleost, Cyprinus carpio.

Methallibure treatment of mature Cyprinus carpio causes a marked reduction in the steroidogenesis, as indicated by the fall in 3beta-HSD activity in the gonads. Significance of these results is discussed.


The effects of microinjection of carbachol or hemicholinium into the amygdala on the levels of plasma and adrenal corticosterone in rats.

Microinjections of 0.4 microgram of carbachol into the amygdala caused a rise of corticosterone (CS) in the morning when the prestimulating level of CS was lower. But the same procedure with a larger dose had no effect in the afternoon, when the prestimulating level of CS was higher.


A convenient thin layer chromatographic method for the detection of cyclochlorotine and simatoxin, toxins from Penicillium islandicum Sopp.

A rapid, convenient TLC method is described for detection of cyclochlorotine, a carcinogen produced by the commonly found storage mold Penicillium islandicum Sopp. This method has also led to the isolation of a new toxic metabolite, simatoxin.


Neuromuscular junction blocking agents: an initial screening bioassay.

A simple, rapid and sensitive in vivo bioassay for the initial screening of neuromuscular junction (NMJ) blocking agents has been accomplished. The i.v. retro-orbital plexus (IVROP) mode of injection was utilized, for the first time, in conjunction with the mouse inclined screen bioassay.


Contraceptive patterns and premarital pregnancy among women aged 15--19 in 1976.

About 780,000 teenagers experience a premarital pregnancy each year. If they weren't using contraception, an additional 680,000 would become pregnant--a total of 1,460,000. However, if all who did not want a baby were practicing contraception consistently, we could reduce the number of pregnancies by at least 313,000. Only 467,000 would become pregnant, and half of these pregnancies would be wanted.


The hundred million dollar misunderstanding.

An Alan Guttmacher Institute survey finds that a total of $215 million was spent on family planning clinic programs in 1976--$155 million from DHEW. DHEW estimates that it spent about $249 million. But the DHEW estimate includes funds for sterilizations, abortions, social work, information and private physician services.


Abortion: subjective attitudes and feelings.

The decision to terminate a pregnancy is neither casual nor easy. Most women see abortion as a difficult but necessary alternative to an unintended birth. Their ambivalence is no reason to counsel against the abortion. Most resolve their problems soon after the procedure. Lack of support by partners can be a major source of distress.


The unmet need for birth control in five Asian countries.

The unmet need for family planning services is remarkably constant across all five countries because of the interaction of fertility intentions and fertility control: as more women use contraception, more of them want fewer children.


Unwanted and mistimed births in the United States: 1968--1973.

Unwanted U.S. marital fertility was down to just nine percent by 1973. The largest proportion of unwanted births was reported by poor black women--23 percent--but this group registered the steepest decline in unwanted childbearing of all the poverty-status and racial groups studied.


[Cerebral cortical neuron tolerance to the repeated administration of diazepam].

The depressive action of intravenously injected diazepam on the spontaneous electric activity of the sensomotor cortex neurons was studied in acute tests on rabbits. After introduction of 1 mg/kg of the drug an acute tolerance of a repeat introduction of it in the same dose developing 40--60 min following the first injection was observed. Earlier after the first injection (up to 20--40 min) the tolerance was lacking. It is suggested that the tolerance of a repeat introduction of diazepam is due to a concurrent blocking of the nervous tissue receptors sensitive to diazepam by the products of its (diazepam) metabolism.


[Mechanism of action of lithium salts on the ethanol predilection by rats].

Lithium chloride with its intraperitoneal administration to rats in a dose of 35 mg/kg, twice a day for 14 days, is shown to suppress predelection for ethanol formed by a 2-month consumption of its 5% solution. This effect of the lithium salt correlates with normalization of the activity displayed by central biorhythms regulators--neurosecretory hypothalamus, nuclei, earlier disorganized by ethanol. A possible relation between the ability of the lithium salts to normalize the central regulation of the biorhythms and their high therapeutic effectiveness in dealing with affective disturbances with a periodic course is discussed.


[Effect of ether anesthesia on pentosephosphate cycle dehydrogenase activity in different parts of the brain].

Investigations carried out on 19 dogs demonstrated that under ether anesthesia and with the anesthetic concentration in the arterial blood of 126.4 +/- 15.4 mg% the activity of the glucose-6-phosphate and 6-phosphogluconate dehydrogenases in the optic and auditory areas of the brain cortex as well as in the median thalamus experiences no significant changes.


[Effect of iprazid on serotonin inactivation by lung tissue].

Tests on isolated perfused lungs of albino rats were conducted to study the effect of iprazide (5.10(4) M) on inactivation of serotonin (5-OT) by the pulmonary tissue. Iprazide does not noticeably inhibit the inactivation of 5-OT, but it greatly reduces the activity of pulmonary monoaminoxidase, the consequence of which is accumulation of appreciable amount of 5-OT in the lungs. The 5-OT protected against destruction amasses in the cytoplasm and is not bound with cellular organoids.


[Membrane-ionic mechanism of the depressing action of adrenaline on giant neurons].

The depressing action of epinephrine on the giant neurons is due to a progressively increasing passive potassium conductivity of the membrane, hyperpolarization and derangement of its generating properties. The triggering factor in the mechanism of the developing epinephrine hyperpolarization is an epinephrine induced increment of passive potassium conduction of the neuronal membrane.


[Selective action on hypophyseal gonadotropic function of a new compound from the group of aromatic series sulfur derivatives].

Chronic experiments set up on rats showed the new original drug izm-931, a sulphoderivative of the aromatic series with a rigid molecular structure, to produce, depending upon its dose and reactivity of the hypothalamus-hypophysogonads, regulation system both stimulating and inhibiting gonadotropic effect. At the same time the drug produces neither peripheral nor estrogenic and antiestogenic action on the uterus and vaginal epithelium. The drug resembles but has a number of advantages over and differences with an earlier synthetized by the authors drug sigetin, whose pharmacological properties are close to the one under consideration. The synthesis and study of compounds of this kind are aimed at the search for new effective medicinal agents with an elective type of action on the gonadotropic function of the hypophysis which are of interest for the obstetric and gynecological practice. The present investigation is a new step towards solving this urgent problem of pharmacology in dealing with neuroendocrine regulation of the reproductive function.


[Thrombolytic action of a heparin-ocrase complex].

The thrombolytic action of the complex heparin-ocrase on the experimentally formed fresh thrombi obtained through intravenous introduction of thrombin into an isolated length of the jugular vein was compared against the effect produced on the thrombi by equivalent amounts of individual components of the complex, i.e. heparin and ocrase. Investigations revealed a lysis of experimental fresh thrombi after intravenous injections of the complex heparin-ocrase and this lysis supervened quicker than following the action of equivalent amounts of ocrase. Heparin used in a dose equivalent to its content in the complex did, as this has been presumed, exercise no thrombolytic action at all.


[Effect of theophylline and isoprenaline on N-acetylation activity in the rat liver].

The activity of N-acetyltransferase is shown to significantly rise after administration of theophylline and isoprenaline, but not of propranolol and N-acetylderivate of para-aminosalicylic acid to form during 30 minutes at a constant rate that increases following addition of cyclic AMP to the incubation medium. The capacity of the rat to acetylate paraaminosalicylic acid did not change under the effect of the mentioned agents.


[Protective action of vitamins and amino acids against the cytotoxic effect of phosphamide and Acrex].

Tests on a culture of embryonal fibroblast cells furnished preliminary data on a possible use of vitamins C, PP, folic acid and methionine in preventing the toxic effects of phosphamide and acrex. An appreciable lowering of the degeneration factor in cultivated cells produced by the cytotoxic action of phosphamide was noted in the presence of vitamin C, methionine, folic acid, choline hydrochloride and vitamin PP and of that exerted by acrex-by adding into the incubation medium of vitamins B1, B2, C, PP, folic acid or methionine. It is advisable that these substances be subjected to a continued investigation in animals with a view of elaborating practical recommendations for their utilization in preventing toxic effects of pesticides on the human organism.


[Dioxidine in experimental pyocyanic pyelonephritis in rats].

A model of obturation hematogenous pyelonephritis was reproduced in rats by infecting them with Pseudomonas aeruginosa. On the model subject to study was chemotherapeutic activity of dioxidine (50--100 mg/kg per day) as compared to gentamycin (5 mg/kg per day). The drugs were administered intramuscularly for 7 days, starting 24 hours after inoculation of the animals. The action of both dioxidine and gentamycin on lethality, bacteriura, the mass of the kidneys and macroscopic changes in them was approximately the same, but dioxidine extered a greater influence on the seeding rate of the causative agent coming from the kidneys. Both drugs fail to bring about complete recovery of the animals.


[Experimental data on the toxic action of hydrazine sulfate on the body and on a tumor].

Toxic action of hydrozine sulfate in rats and mice along with its influence on the mitotic activity of Walker carcino-sarcoma cells were studied. Single injections of the agent in high doses resulted in destruction of the animals during the first 2 days with no "delayed death" observed. Multiple injections caused a considerable loss of body weight. When given in toxic doses the agent did not influence hemopoiesis, but did affect sensitivity, drastically increasing the toxic action of ethanol or barbiturates. Administration of hydrazine sulfate in therapeutic doses decreased markedly the mitotic activity and increased the appearance of atypical mitotic cells.


[Effect of phenobarbital on sulfanilamide acetylation].

By using the "turned inside out bag" technique and brough tests with homogenates it was found that sulfanilamide is susceptible to acetylation in a larger measure than sulfocarbamide and sulfacylum natrium. In tests with isolated lengths of the small intestine phenobarbital (in doses of 25 mg/kg for 5 days) weakened acetylation of sulfanilamide and sulfocarbamide and did not change acetylation of sulfacylum natrium. Acetylation of all these three sulfanilamides in homogenates of the liver, blood and the small intestine mucosa did not change under the effect of phenobarbital.


[Diuretic activity of benzimidazole urea derivatives].

The chemical structure of benzimidazol urea derivatives and physico-chemical properties of these compounds conditioned by it play a significant role in the manifestation of the emictory effect. Among the study substances a number of compounds displaying a marked, but short-lived diuretic action have been educed. In the manifestation of emictory properties in benzimidazol urea derivatives of importance is the character of the side chain and its ramification and also an even number of carbon atoms in the acyl radical.


[Effect of aggregation inhibitors on thrombocyte enzymatic activity].

Experiments on rabbits proved that amidopyrin, sulphatizonicotinoilamine-guanidine, chlorpromazine, triphthazine, euphylline and tedamine inhibit aggregation of thrombocytes and unidirectionally have an effect on the carbohydrate metabolism enzymes in these cells, both in vitro and in vivo following their single and coursewise introduction. They also activate the lactate- and glyceraldehide-3-phosphate-dehydrogenase and reduce the activity of glucose-6-phosphate-dehydrogenase.


[Effect of morphine and fentanyl on evoked potentials in the brain under various conditions of dental pulp stimulation].

The effect of morphine and phentanyl on the potentials in the cortex of the large hemispheres, thalamus and midbrain developing with different modes of the dental pulp stimulation was studied in cats. Morphine (1--2.5 mg/kg) and phentanyl (0.05--0.1 mg/kg) above all bring down the potentials amplitude in associative and nonspecific structures with rhythmic stimulation and eliminate post-activation relief. With the morphine donse rising to 2.5--10 mg/kg and that of phentanyl--to 0.1--0.2 mg/kg the responses in mono-and bipolar, sub- and supramaximal and paired stimulation become weaker. With these types of stimulation the potentials amplitude decreases roughly in the same measure. The evoked responses in specific afferent pathways experience less marked changes than do potentials in the associative and nonspecific structures.


[Experimental study of azathioprine in nephrotoxic nephritis in rats].

In tests conducted with 165 mongrel sexually mature and immature rats it is shown that azathioprine used in nephrotoxic nephritic improves the general condition, reduces the edema of subcutaneous cellular tissues, as well as the intensity of proteinuria and helps retaining its selective type, lessens the degree of hypo- and dpsproteinemia and, especially, of hyper-beta-lipoproteinemia; in the kidneys the pathomorphological changes characteristic of nephritis become less marked. Azathioprine does not influence the process of acido-and ammoniogeness in the tubuloar system of the nephron, nor does it modify diuresis. The effect of azathioprine is most spectacular in the acive phase of developing nephritis. In rattlings with nephritis theaction af azathioprine in regard to a number of factors (proteins, beta-lipoproteids, gamma-globulins of the blood) is somewhat stronger than in the sexually mature rats.


[Nature of the sensitizing influence of urea on the effects of catecholamines].

Tests conducted on aortic strips of rabbits, portal veins and musculus rectococcygeus in rats showed the urea to nonspecifically increase the effects of norepinephrine at the expense of a greater calcium permeability of membranes and, possibly, also at the expense of a higher sensitivity of the myosin adenosine-triphosphatase to the action of calcium ions without affecting the function of adrenoreceptors.


[Effect of fentolamin on carbohydrate-phosphorus metabolic indices of the rat myocardium in the early periods of body growth].

The effect of alpha-adrenoblocking agent phentolamine (1 mg/kg) on the ATP, ADP, AMP, inorganic phosphorus, glycogen in the heart muscle of rats of different age (7,30 and 3 1/2 month old) was investigated. It is shown that the nature of changes in the studied factors testifies to a greater sensitivity of the myocardium to the alpha-adrenergic block at early stages of the post-natal ontogenesis.


[Effect adrenaline and ephedrine against a background of aminazine on systemic, cerebral and extracerebral hemodynamics].

Experiments with anesthetized cats demonstrated chlorpromazine (2 mg/kg) to pervert the vasopressor action of adrenaline (5 mkg/kg) and ephedrine (2 mg/kg) on the systemic arterial pressure, cerebral and extracerebral tonicity of the vessels. The authors believe that with chlorpromazine pretreatment the adrenomimetics produce a selective stimulation of the beta-adrenergic receptors, this accounting for the observed depressor effect.


[Effect of lithium chloride on the excitability of the subcortical structures of the rabbit brain].

Lithium chloride microinjections in doses of 100 mkg/mkl into the brain structures of rabbits produce a depressive effect on the subcortical formations. The drug brings down the excitability of the hippocampus, caudate nucleus, mesencephalic reticular formations, thalamus and hypothalamus, raising the excitability of the amygdalae.


[Effect of cordarone on blood circulation under general anesthesia and in free behavior].

Experimental data on the effect of cordarone (10 mg/kg) upon blood circulation in animals under general anesthesia and in free behavior are presented. It was established that under general anesthesia cordarone induced in animals hypotension (16 +/- 2%), bradycardia (19 +/- 1.82%), heart contractility inhibition (29 +/- 6.10%). In animals under conditions of free behavior cordarone causes hypertension (9 +/- 3.1%), tachycardia (11 +/- 1.3%) and potentiates cardiac contractility. Practolole, a selective beta1-adrenoblocking agent, potentiates the effect of cordarone on the myocardium and also obliterates the difference between the effects of the drug in animals under general anesthesia and in free behavior. These data point to the drug exerting a direct inhibitory effect on the myocardium. It is suggested that the difference in the effects of cordarone in animals under general anesthesia and in conditions of free behavior is due to a lesser degree of activation produced by the drug in anesthetized animals.


[Mechanism of action of Novocain administered intravenously to animals].

Tests conducted with 48 dogs and 100 rabbits demonstrated that intravenous administration of novocain has a well-marked positive influence in extreme conditions, such as massive blood losses and traumatic shocks. It is shown that in the mechanism of the drug's action particularly important is its capability to increase the cardiac performance, to eliminate spasms of resistive vessels and to contract the blood-carrying vessels of the microcirculatory stream. The final effect, however, is in a great measure dependent upon the initial functional state of the organism (the period of hemorrhagic or traumatic shock) and an early introduction of the drug.


[Action of barbituric acid derivatives on the physiocochemical properties of DNA].

The action of barbituric acid derivatives--phenobarbital, sodium ethaminal and sodium amytal--on the physico-chemical properties of mucleic acids was studied. It is shown that as compared to sodium ethaminal and sodium amytal phenobarbital exerts a more potent action on the secondary and tertiary structure of native DNA molecules.


[Alkyl derivatives of imidazole dicarboxylic acid diamides as inhibitors of the mitochondrial respiratory chain].

The effect of alkyl derivatives of imidasol-dicarboxylic acids diamides was investigated in vitro on the liver mitochondria of rats with tese derivatives being added into a cuvette for measuring in millimolar concentrations their action on the function of mitochondria, viz- the electron transport in the respiratory chain and oxidative phosphorylation. The study substances were found to inhibit the chain of the electrons transport to the mitochondria on the level of the NADN-dehydrogenase. The inhibitory activity rises in the series: norantipheine, antipheine, allylnorantipheine, propylnorantipheine, ethephil and ethimizol. Besides, ethephil is an inhibitor that blocks the transport of electrons between cytochromes "b" and "c".


[Effect of pharmacological agents on the membrane hydrolysis of saccharose].

Membranous hydrolysis of saccharose (membranous digestion) and synthesis of invertase in the intestinal epithelial cells of rats and mice following introduction of pharmacological agents were studied. Ethyl alcohol, luminal and atropine lowered both the invertased activity in the area of membranous digestion and the synthesis of the enzyime. Hexonium and pilocarpine also lowered the level of membranous hydrolysis, but not the formation of enzymes. Epinephrine and octadine, on the contrary, enhanced the intensity of both these processes. The disclosed pharmacological effects are considered in the light of features specific for the structural organization of enzymes in the area of membranous digestion.


[Effect of thyrocalcitonin on mineral metabolism in experimental osteoporosis].

By the method of radioactive indication of ashed specimens of the femur, tibia, jaw bones and molars on a model of experimental osteoporosis in rats it is shown that the degree of mineralization of calcified tissues increases under the effect of thyrocalcitonin (TCT). The hypermineralization of jaw bones and, especially, of molars was attended by a lower 45Ca inclusion in these tissues. The structure of the adrenal cortex, kidneys, pancreas and thyroid returned back to normal under the effect of TCT and with carbohydrate rich nutrition, this occurring against the background of a high 45Ca concentration in these organs.


[Effect of dihydroergotamine, reserpine and anapriline on the pharmacokinetics and metabolism of norsulfazole in rats].

In in vivo experiments with rats anapriline (1 mg/kg) greatly reduced the level of gastrically introduced norsulfazol (200 mg/kg) in the blood, liver, kidneys, stomach, small and large intestine both in healthy rats as well as in those with experimental gastritis provoked by acetylsalicylic acid twice introduced into the stomach. Under the influence of anapriline the acetylization of norsulfazol in the liver would become 4.7 times less intensive. Dihydroergotamin (10 mg/kg) did not influence the absorption, distribution and acetylization of norsulfazol. Reserpine (10 mg/kg) brought down the amount of free norsulfazol in the gastro-intestinal tract and reduced the quantity of acetylized norsulfazol in the blood, stomach, small and large intestines. The acetylization changes in the kidneys were not significant. In the springtime the intensity of the norsulfazol acetylization increases by more than twice. The described results bear witness to the participation of beta-adrenoreceptors in the transport and metabolism of norsulfazol.


[Anabolic action of flavonoids].

Flavonoids robinin and hyperin lengthen the average survival time of albino mice subjected to bilateral nephrectomy when introduced to the animals intraperitoneally in different doses. The effect of the study substances is inferior to that of dianabol with EU20 of robinin amounting to 82 mg/kg, of hyperin--88 mg/kg and that of dianabol--4.2 mg/kg. The methioned agents and also flavonoid lespedine enlarge the body mass and that of the musculus levator ani in growing castrated rats, when introduced by the intra peritoneal route in a dose of 100 mg/kg. Flavonoid robinin produces the greatest anabolic effect in tests set up both on mice and rats. The data obtained allow the spectrum of the biological action of flavonoids to be extended to some of their positive influence on the catabolic-anabolic processes.


[Therapeutic effectiveness of acetylcysteine in acute dichloroethane poisoning].

With its multiple administration acetylcysteine is shown to display a marked curative effect in acute poisoning of animals (rats, mice, rabbits) with ethylene dichloride. It increases the survival of animals and largely prevents disorders in hemopoiesis and in the blood coagulation system, minimizing toxic lesions of the liver and kidneys.


[Effect of x-ray contrast substances on the metabolism of xenobiotics and steroid hormones by rat liver microsomes].

Uro- and cholecystographic contrast media are shown to be capable of changing the rate of oxidative hydroxylation of amidopyrine and steroid hormones. The degree and duration of the diminishing rate of the xenobiotics and steroids metabolism are determined by concentrations of the X-ray contrast media in hepatic cells and the rate of their clearance.


[Cysteine activity in the poisoning of animals by various aliphatic series halogenated hydrocarbons].

In poisoning animals with various aliphatic series haloid-hydrocarbons (LK99 and LD99) free cysteine was found to be a group antidote in rats poisoned with monohaloid-hydrocarbons. It was established that the therapeutic activity of cystein depends not on the nature of haloid and double bonds, but on the number of the haloid atoms in a molecule, the length, ramification and nature of the radical. A good durative action are shown by such cystein derivatives as acetyl-cysteine, glutathione and cystein salts. In poisoning with haloid-alkyls dithiol antidotes (unithiol, mecaptide, BAL) and other drugs proved ineffective.


[Toxicological properties of a cephedrine preparation].

The antidepressant drug cephedrine experimentally displays a little acute and chronic toxicity, does not influence the development of allergic reaction in guinea pigs, changes but little the ECG and does not possess teratogenic and embryotoxic properties. When used in a subtoxic dose it is capable of causing dystrophic changes in individual neurons in the cortex and subcortical formations of the central nervous system, to delay the growth of fetuses, especially when administered during the second half of gestation.


The intramural role of the NIH as a biomedical research institute.

An investigation of the NIH role as a biomedical research institute is reported, based on counts of articles, notes, and reviews in 1,000 biomedical journals covered by the Science Citation Index from 1973 to 1975. Investigators at the NIH produce more biomedical research papers per year than any other group in the U.S., accounting for approximately 3.4% of all U.S. biomedical research papers. The NIH papers show a strong emphasis at research Level 3, clinical investigation, which is the most basic and scientific level of research focused directly on disease in man. On a clincial-to-basic science continuum the NIH emphasis on clinical laboratory research represents a position that is midway between the more clinical research being performed at medical schools and the more basic research being performed in graduate departments of universities. The papers of the NIH intramural scientists appear in highly influential journals. In the mid 1970's, the rate of NIH intramural publication is particularly high in the subfields of biomedicine that are most closely related to research on cancer.


Slow repetitive activity from fast conductance changes in neurons.

Membrane properties of molluscan neural somata and crustacean axons have been studied by voltage clamp analysis. These neurons generate rhythmic discharge in response to constant current stimulation, and in certain of the molluscan neurons the discharge is spontaneous. Atransiently activated potassium conductance is prominent in both of these types of neurons. Computer simulations have been run in which this transient conductance system was incorporated into modified versions of the Hodgkin-Huxley equations. Repetitive discharge is generated that is very similar to the response of the preparation from which the simulation parameters were derived. Rhythmic, spontaneous discharge is generated on slight modification of the conductance parameters.


Possible mechanisms underlying bursting pacemaker discharges in invertebrate neurons.

Certain invertebrate neurons generate endogenous bursts of action potentials due to an underlying slow membrane potential oscillation. An early hypothesis for the oscillations proposed a high resting sodium conductance that led to the depolarizing phase, followed by activation of an electrogenic sodium pump coupled to chloride ions, leading to the hyperpolarizing phase. Recent findings contradict this hypothesis. Current thought implicates two conductances in the generation of the oscillations. The depolarizing phase is due to an increase in a sodium or a calcium conductance; the hyperpolarizing phase is due to a subsequent increase in a potassium conductance, which may be either voltage dependent or triggered by an influx of calcium ions. The observation of a negative slope conductance region in the membrane I-V characteristic supports this hypothesis. Bursting cells also usually exhibit anomalous rectification, i.e., a decrease in slope conductance with depolarization, in the I-V characteristic. This decrease may result from a decrease in an outward current or an increase in an inward current. The more important bursting membrane characteristics have been incorporated into an electronic analog. The analog confirms the appropriateness of the two-conductance hypothesis. It also suggests that potassium ion accumulation outside the cell membrane may enhance bursting activity.


Comparative studies of firefly pacemakers.

Rhythmic flashing behavior of synchronous flashing fireflies from Malaysia and New Guinea was studied. The "circa second" firefly pacemaker has characteristics analogous to circadian rhythms, such as entrainment, phase shifting, limits of entrainment, fringe entrainment, and effects of the light:dark ratio on phase. The three species studied show different phase-response curves; a light pulse causes a large phase shift in one firefly species (Pteroptyx cribellata) but small phase shifts in others (Pteroptyx malaccae and Luciola pupilla). Comparative studies of the phase angle differences between the animal's flash and the flash of a controlled light source suggest at least two different mechanisms of attaining synchrony: 1) by cycle-to-cycle phase shifting of a stable oscillator; 2) by changing the underlying period (tau) of a variable oscillator.


Nociceptive responses of neurons in the posterior group of nuclei and medial thalamus.

Anatomical studies have shown that fibers of the spinothalamic tract terminate in both the posterior group of nuclei (PO) and the nuclei of the medial thalamus. Only the PO receives fiber terminations from the spinocervicothalamic and dorsal column-medial lemniscal projections. This difference in connectively is reflected in the functional differences between the neurons in the PO and those in the medial thalamus. Although both PO and medial thalamus contain a large proportion of nociceptive neurons, only the PO contains neurons that have "lemniscal" response properties. Lesion studies have demonstrated the importance of the spinothalamic tract in mediating A and C fiber input to nociceptive neurons in the PO and medial thalamus. These studies showed that the nociceptive neurons in PO also receive A fiber input from the dorsal column-medial lemniscal projection and A and C fiber input from the spinocervicothalamic projection.


Integration of sensory input in laminae I, II and III of the cat's spinal cord.

There is a growing body of evidence supporting the concept of pain as a specific sense. There are afferent fibers from the skin that respond only to noxious stimuli, the nociceptors. Some nociceptor afferents have small myelinated axons (Adelta) while the rest have unmyelinated axons (C). Among the neurons in the superficial layers of the spinal cord (laminae I, II and III) in the cat is a population that responds exclusively to noxious cutaneous stimuli. This input arrives over the nociceptor afferents. Another population responds best to mild temperature changes, reflecting an input from the thermoreceptive afferents. Many units in these two populations of spinal neurons have been shown to project to the brainstem. Therefore, they comprise a relay to the brain for nociceptive and thermal information. Another population of superficial neurons in the spinal cord responds to gentle mechanical stimuli, particularly to slow movement. They reflect an input from the C mechanoreceptor. This population is characterized by spatal and modality convergence. They do not project to the brain and their functional role is still unknown.


Development and organization of multimodal representation in cat superior colliculus.

The present paper examines developmental and organizational parallels between visual and nonvisual cells in the cat superior colliculus (SC). An attempt is made to relate these developmental and organizational features to the role the SC plays in orientation behavior. In young kittens visually guided behavior is virtually nonexistent and requires many weeks to develop. Similarly, kitten SC cells are unresponsive to visual stimuli until at least 7 days after birth, and it is only after many weeks that SC cells behave as do those of the adult. In contrast to the development of visual cells, however, some neurons responsive to somatic stimuli are present in the SC on the day of birth, and cells responsive to acoustic stimuli appear several days later. Thus, the sequence in which modality represenstation appears in the cat SC parallels the developmental chronology of the use of different sensory cues for orientation. These data indicate that the functional roles of the visual, somatic, and acoustic representations may be similar. The finding that the organization of the somatic representation in the SC is similar to, and in register with, the visual representation is consistent with this possibility. It is suggested that the SC can utilize cues from a variety of modalities in order to facilitate appropriate orientation behavior.


Anatomical asymmetry as the basis for cerebral dominance.

Despite repeated assertions by some critics of the impossibility of linking behaviour to study of the brain, there have been major, although not always continuous advances in this field over the past 100 years, some of them based on simple techniques. One example is the study of cerebral dominance, for which it was believed until quite recently that no anatomical basis had been specified. The paper summarizes the findings of striking anatomical asymmetry of the upper surface of the temporal lobe, in an area known to be involved in speech functions. Asymmetries observed in autopsy brains of adults and fetuses, both by gross and by cytoarchitectonic techniques, are reported. By use of radiological methods asymmetries have been shown in the brains and skills of living persons. Asymmetries also appear to be present in the endocasts of skulls of ancient humans, and in nonhuman primates. The distribution of asymmetries is different in left and right handers. The implications of these findings are discussed.


Current management of the amenorrhea-galactorrhea syndrome.

Management of the amenorrhea-galactorrhea syndrome has changed considerably in the last 5 years. Better understanding of the neuroendocrine physiology of the central nervous system in general, and of the hypothalamic-pituitary region in particular, have contributed significantly to our understanding of the pathophysiology of this syndrome. Greater awareness by physicians, improved neuroradiologic techniques, and the development of immunoassays for prolactin have markedly improved our diagnostic abilities. Many more patients are being diagnosed as having a pituitary tumor. The recent introduction of microneurosurgical techniques and the new medications (ergolines) are changing the treatment of this syndrome. Women in the childbearing age--who are affected most often--can expect successful treatment in the majority of cases with resumption of normal menstrual function and fertility. However, certain risks are still posed, particularly during pregnancy. In spite of improved diagnosis and treatment, the natural history of prolactin-secreting pituitary tumors and the long-range effects are still not fully appreciated. More experience in time will be needed before the indications for and the efficacy of various treatment regimens are fully known.


The purine nucleotide cycle in skeletal muscle.

The following evidence demonstrates that ammonia production in muscle occurs via the reactions of the purine nucleotide cycle: i) Extracts of cytosol which lack glutamine dehydrogenase produce ammonia under conditions that mimic muscle doing work. In such extracts a member of the purine nucleotide cycle (AMP, IMP, or adenylosuccinate) must be present in order that ammonia production can take place, ii) Perfused hindleg of rat or hindleg in situ produces ammonia during exercise, and there is a concomitant production of IMP and adenylosuccinate. Exercise causes a decrease in the contents of glutamate, aspartate, and glutamine and an increase in the content of alanine of perfused hindleg of rat. However, output of alanine does not change or is diminished during exercise. Glutamine output is diminished by exercise. Epinephrine increases the output and tissue content of ammonia and glutamine. It decreases the output and content of alanine, and it decreases the contents of aspartate and glutamate.


Microvascular transplantation of the human fallopian tube.

An unsuccessful human fallopian tube transplant is reported. A microsurgical technique is described which initially secured a viable transplant. However, the allograft subsequently died, probably as a result of rejection. Immunosuppression of the patient caused no complications or difficulties, the donor sharing one HL-A haplotype with the patient. The operative procedure, the risks of immunosuppression, and the ethical aspects of the case are discussed in order to present the problems associated with fallopian tube transplantation.


Pituitary adenomas associated with elevated blood follicle-stimulating hormone levels: a histologic, immunocytologic, and electron microscopic study of two cases.

The histologic, immunocytologic, and electron microscopic features of pituitary adenomas surgically removed from two men with elevated levels of blood follicle-stimulating hormone (FSH) are described. In both cases, the high blood FSH levels were reduced after surgery. By light microscopy, the tumors corresponded to chromophobic adenomas, and the immunoperoxidase technique revealed the presence of immunoreactive FSH (beta-subunit) in the cytoplasm of the adenoma cells. By electron microscopy, the adenoma cells differed considerably from nontumorous FSH cells. They were smaller and angular and contained numerous microtubules as well as spherical secretory granules measuring 100 to 250 nm in diameter and often lining up along the cell membranes. The present findings are consistent with the view that FSH-producing adenomas may originate in the human pituitary.


Spontaneous pregnancy in women with a prolactin-producing pituitary adenoma.

The occurrence of spontaneous pregnancy in patients with amenorrhea-galactorrhea, hyperprolactinemia, and radiographic evidence of a pituitary tumor is unusual. We present here two patients who conceived spontaneously. One had an uneventful pregnancy. Following delivery, transsphenoidal pituitary surgery was performed, confirming the presence of a prolactin-producing adenoma. The second patient had an early pregnancy termination (at 12 weeks of gestation). These patients provide evidence that ovulation and pregnancy can occur in spite of elevated prolactin levels.


Pregnant mare's serum gonadotropin. IV. Induction of premature labor by pregnant mare's serum gonadotropin and its prevention by using clomiphene or indomethacin.

The administration of pregnant mare's serum gonadotropin (PMSG), 30 IU on day 18 of pregnancy, resulted in premature labor in rats. However, this abortifacient efficacy of PMSG was not demonstrable when a simultaneous injection of progesterone, clomiphene, or indomethacin was scheduled, thus suggesting that the action of PMSG is medicated by the estrogen-stimulated release of prostaglandin. The termination of pseudopregnancy in bilaterally hysterectomized rats by PMSG and its reversal by indomethacin revealed that the inhibition of luteal function by PMSG does not require the presence of a uterus.