Noradrenaline inhibition of acetylcholine release from guinea-pig brain. The effect of noradrenaline (NA) on acetylcholine (ACh) release from guinea-pig brain was investigated in superfused cerebral cortex slices and in unrestrained unanaesthetized animals provided with epidural cups. The amine reduced the ACh release from electrically stimulated tissue and its effect was antagonized by phentolamine and phenoxybenzamine, but not by propranolol and spiroperidol. The injection of NA (150 microgram) into the cerebral ventricles caused sedation, E.Co.G. synchronization and reduced ACh outflow from the parietal cortex. This inhibition was counteracted by alpha-blocking agents. A lower dose of NA (50 microgram) did not change the behaviour, but produced a late increase in ACh outflow, prevented by spiroperidol. These results fit well with the hypothesis that NA restrains, via alpha-receptors, the ACh secretion from the nerve endings and indirectly support the view that the amine reduces the firing rate of the corticopetal cholinergic neurones. The late increase in ACh outflow, observed in vivo, may be referred to secondary activation of the dopaminergic neurones, known to enhance the cortical ACh release in this animal species.


Neuronal and non-neuronal components in the overflow of labelled adenyl compounds from guinea-pig taenia coli. Guinea-pig taenia coli preprations were pre-incubated in 3H-adenosine and the overflow of 3H-compounds to a superfusing medium was measured during transmural field stimulation in the presence and absence of tetrodotoxin. The fractional overflow of 3H-compounds on stimulation of taenia coli pre-incubated in 3H-adenosine at 10(-7) M was greater than after incubation at 10(-5) M. About half of the releasable store was blocked by tetrodotoxin. It is proposed that at lower concentrations, there is selective loading of a releasable store, while at higher concentrations thare is a greater loading of non-releasable stores, and that neuronal stores account for about 33% of the 3H-compounds released by transmural stimulation.


Potassium-induced release of enkephalins from rat striatal slices. The rate of release of enkephalin from rat striatal slices increased 7--10 fold in response to depolarization by 50 mM potassium ions in vitro. The potassium-evoked release of enkephalins was abolished in a calcium deficient medium. Uptake studies indicated that the potassium-stimulated efflux was not due to the inhibition of an active uptake mechanism for these peptides. These findings provide support for the view that enkephalins may function as neurotransmitters in brain.


Antiextensor effects of 3,3-diphenyl-n-propylamine in the mouse. Diphenylpropylamine has antiextensor activity in the MES test and worsens clonic seizures produced by pentylenetetrazol. The drug also prevents tonic hindlimb extension produced by large doses of pentylenetetrazol. Diphenylpropylamine appears, therefore, to be a phenytoin-like compound. However, unlike most antiextensor agents, diphenylpropylamine has neuroexcitatory effects and antagonizes barbital-induced loss of the righting reflex.


The effect of 6-hydroxydopamine on the antinociceptive action of morphine. The role of brain catecholamines in the antinociceptive action of morphine was investigated. Intraventricular 6-hydroxydopamine which depleted brain noradrenaline in the rat had no effect on morphine's antinociceptive action but combined treatment with pargyline and 6-hydroxydopamine to further deplete brain dopamine potentiated morphine's action. It was also shown that when dopamine receptors were blocked, the antinociceptive action of morphine was potentiated whereas alpha- and beta-adrenoceptor antagonists had no effect. 6-Hydroxydopamine had two effects in mice tested on the hot-plate. It produced a hyperalgesia and antagonized the antinociceptive action of morphine. This antagonism of morphine appeared to be the result of the depletion of noradrenaline rather than dopamine. Intraventricular injection of both catecholamines restored the antinociceptive action of morphine in 6-hydroxydopamine-treated mice but dopamine was ineffective in the presence of a dopamine beta-hydroxylase inhibitor. It is suggested that the antinociceptive action of morphine is expressed by noradrenergic neurones in the mouse and by both noradrenergic and dopaminergic neurones in the rat.


The effects of stimulants and inhibitors of histamine receptors on acid secretion from guinea pig gastric fundus. Two selective H2 receptor stimulants (5-methyl-N-methylhistamine and dimaprit) so far never tested in isolated gastric preparations, were found to be strong stimulants of acid secretion from the guinea pig isolated gastric fundus. Although some differences were observed in the cumulative dose--response curves for these two agonists, the peak responses obtained were not significantly different from the maximum response to histamine. Cimetidine produced parallel displacement of the dose--response curves to the right with the maximum response unchanged, suggesting competitive antagonism of H2 receptors. The dose--response curve for histamine was not affected by the simultaneous administration of an H1 receptor agonist, 2(2-aminoethyl)thiazole, or of an H1 receptor antagonist, pyrilamine. This indicates that the action of histamine on the isolated guinea pig gastric fundus is associated exclusively with H2 receptor stimulation.


Pharmacological characterization of benzodiazepine receptors in the brain. Receptors in rat brain membranes which specifically bind 3H-diazepam were characterized pharmacologically using reference substances representing several pharmacological classes of drugs. Of 28 benzodiazepines tested, several "classical" ones (diazepam, clonazepam, lorazepam, oxazepam, nitrazepam, flurazepam, bromazepam and chlorazepate) with known clinical efficacy, as well as three newer "triazolo" benzodiazepines (estazolam, U 35,005, U 31,957), one new "imidazolo" benzodiazepine, U 31,219, and one new 2-carbamoylmethylene-benzodiazepine, displaced 3H-diazepam binding at low concentrations (Ki=1--60 nM). For these benzodiazepines there was a stastically significant correlation between Ki values for displacement and ED50 (or MED) values in several pharmacological tests predictive of anxiolytic activity in man. More than 100 nonbenzodiazepines, representing 22 distinct pharmacological classes as well as 14 presumed neurotransmitters in the CNS, including 4 peptides, were much weaker as 3H-diazepam displacers (K2 greater than 0.1 nM). These results suggest that in vitro 3H-diazepam binding represents the physiologically relevant binding to hitherto unknown receptors in the CNS.


Mechanism of the cardiovascular activity of dibenzoxazepine in cats. Small i.v. doses of dibenzoxazepine (DBO) (50--400 microgram/kg) given to anesthetized cats resulted in dose related increases in heart rate (up to 70 beats/min) and blood pressure (up to 80 mm Hg). The pressor response was blocked by pretreatment of the animals with phentolamine; pretreatment for 3 days with 6-hydroxdopamine; with mecamylamine and spinal transection between C1 and C2 but not by propranolol or adrenalectomy. The increase in heart rate was blocked by pretreatment with propranolol, 6-hydroxydopamine, mecamylamine and spinal transection whereas adrenalectomy only affected the response slightly. DBO produced only negative effects on the isolated rabbit heart. Bioassay of arterial blood showed an increased level of circulating catecholamines corresponding to the cardiovascular stimulation. DBO had no tyramine-like activity on the isolated rabbit aortic  strip but slightly potentiated the contraction induced by noradrenaline. These findings strongly suggest that the cardiovascular effects resulted from central stimulation of the sympathetic nervous system. A minor part of the observed sympathomimetic effects may also be the result of the ability of DBO to potentiate the effects of noradrenaline perhaps by blocking catecholamine uptake.


Effects of purine compounds on cholinergic nerves. Specificity of adenosine and related compounds on acetylcholine release in electircally stimulated guinea pig ileum. The action of 21 purine compounds on the twitch response of the electrically stimulated guinea pig isolated ileum has been investigated. Adenosine and related compounds produced a dose-dependent depression of the response. Adenosine was the most potent and 2'-deoxyadenosine had one hundredth the potency of adenosine. Adenine, hypoxanthine, inosine, IMP, ITP, xanthine, xanthosine, XMP, XTP, guanine, GMP and GTP were ineffective at concentrations less than 1 mM. Adenosine (30 microgram) reduced the electrically induced ACh output from the ileal strips. The dose--depression curve for adenosine (0.1--30 microgram) was shifted to the right in the presence of xanthine derivatives and of these, theophylline was the most potent inhibitor of adenosine. On the other hand, dipyridamole (0.1--1 microgram) and hexobendine (0.1--1 microgram) shifted the curve to the left. They markedly inhibited 3H-adenosine uptake into the ileum. Theophylline (0.1 mM), dipyridamole (0.3 microgram) and hexobendine (0.3 microgram) did not affect tetrodotoxin-, adrenaline-, strychnine- and morphine-induced inhibition of the twitch response. The present investigations have revealed that adenosine and related compounds reduce ACh release from the intramural cholinergic nerves in the guinea pig ileum possibly in a specific manner (or through a specific receptor site) different from that of other inhibitors such as morphine.


Biliary spasmolytic action of 3-(2,4,5-triethoxybenzoyl)propionic acid (AA-149) in dogs. The spasmolytic action of 3-(2,4,5-triethoxybenzoyl)propionic acid (AA-149) on the biliary tract was investigated in anesthetized dogs. Intravenous administration of AA-149 at 2 mg/kg and higher doses produced a dose-dependent reduction in passage resistance through the choledochoduodenal junction and in gallbladder pressure, and a dose-dependent increase in bile flow. AA-149, like cholecystokinin, decreased biliary ductal pressure in spite of increasing the bile flow in dogs with ligation of the cystic duct of the gallbladder, whereas taurocholate increased the pressure as well as the bile flow. Moreover, the spasmic response of the choledochoduodenal junction to morphine was depressed strongly by AA-149, BUT NOT CONSISTENTLY BY ATROPINE. The effects of AA-149 were not influenced by pretreatment with atropine, phentolamine or propranolol. These findings strongly suggest that AA-149 relaxed the biliary tract and depressed the morphine-induced spasm by a mechanism different from those of anticholinergic and sympathomimetic agents.


Cardiovascular effects of morphine and opioid peptides following intracisternal administration in chloralose-anesthetized rats. Beta-Endorphin (0.9--2.0 nmol), morphine (11--250 nmol) and D-ala2-met-enkephalinamide (17--33 nmol) administered intracisternally produced preferential vasodepressor responses and bradycardia. Leu- (1.8--180 nmol), met-enkephalin (17--520 nmol) and alpha-endorphin (5.7--57 nmol) administered in the same way produced preferential vasopressor effects and the latter two peptides also produced bradycardia. Results obtained with naloxone (300 nmol) given intracisternally indicate that the pressor and depressor actions as well as the bradycardia are mediated through opiate receptors. The results indicate that opioid peptides may be involved in central cardiovascular control.


GABA potentiates potassium-stimulated 3H-dopamine release from slices of rat substantia nigra and corpus striatum. GABA (10-5--10-3 M) had no effect on the spontaneous outflow of previously accumulated 3H-DA or 3H-5HT from rat nigral or striatal slices. However, GABA markedly potentiated the potassium-stimulated release of 3H-DA in both brain regions, while the depolarization-induced output of 3H-5HT was only slightly increased. This action of GABA was blocked by pictotoxin but not by bicuculline. Amphetamine likewise evoked a dose-related efflux of 3H-DA and 3H-5HT from nigra and striatum, but these releases were unchanged by GABA. The data suggest that GABA acts presynaptically in these areas to regulate dopaminergic cell function.


The relationship between speed and amplitude of the fastest voluntary contractions of human arm muscles. The relationship between the speed of the fastest possible voluntary contractions and their amplitude was examined for several hand- and forearm muscles under isometric and isotonic conditions. The consistent finding was the amplitude dependence of the speed of the fastest voluntary efforts: the larger the amplitude, the faster the contraction. The increase of the rate of rise of isometric tension or of the velocity of isotonic movements with rising amplitude was linear. The slope of this relationship was the same for three different hand- and forearm muscles examined. The duration of the contractions measured from onset to peak was approximately constant for all amplitudes. The duration of the EMG-burst recorded from the contracting muscle was similar as the time from onset to peak of the contraction. These results show that the skeleto-motor speed control system operates by adjusting the velocity of a contraction to its amplitude in such a way that the contraction time remains approximately constant. It is suggested that this type of speed control is a necessary requirement for the synchrony of synergistic muscle contractions.


Forebrain lesions and retention of imprinting in domestic chicks. Newly-hatched domestic chicks were reared separately with one of two types of imprinting object hanging in their cages. On the 5th day discrimination tests demonstrated strong preferences for the familiar object. On the 6th day the chicks were subjected to bilateral aspiration lesions of either the anterior or the lateral forebrain and their imprinting objects removed from the cage. Discrimination tests were made on the 9th and 12th days, the imprinting objects replaced, and a final relearning test given on the 14th day. The anterior lesion group was slightly impaired in the retention and relearning tests while the lateral lesion group was drastically affected, being significantly worse than the anterior group and with choices only just significantly above random expectation in the retention tests and no different from random choice in the relearning test. It was concluded that a lateral forebrain region is necessary for retention and relearning of a previously acquired imprinted preference.


Stages of recovery from central norepinephrine lesions in enriched and impoverished environments: a behavioral and biochemical study. Adult rats were injected intraventricularly with 6-OHDA and allowed to recover for varying time periods in either an enriched colony environment or in isolation cages. When tested behaviorally in a novel environment, isolated animals showed a cyclical recovery pattern, with behavioral changes at 14 days after lesioning which were different from those seen at 2 and 45 days after lesioning. In contrast, animals housed in a colony environment showed progressive improvement and better recovery than isolates. Biochemical studies of uptake of H3NE and histofluorescence indicated that colony housed animals had enrichment effects (higher cortical NE uptake), but they were also more susceptible to 6-OHDA and did not recover well from the lesions. Isolated animals showed somewhat better recovery of NE uptake following 6-OHDA injections, especially in cortex. Because behavioral recovery from 6-OHDA was dissociated from biochemical indicators of recovery in NE circuitry, these results imply that brain systems other than NE were primarily responsible for the enhanced behavioral recovery which occurs in enriched environments.


Integration in descending motor pathways controlling the forelimb in the cat. 4. Corticospinal inhibition of forelimb motoneurones mediated by short propriospinal neurones. A previously described inhibitory trisynaptic cortico-motoneuronal pathway (Illert et al., 1976a) was analysed in order to identify the two relay stations. Intracellular recording was made from motoneurones to elbow muscles. Corticospinal fibres were stimulated in the contralateral medullary pyramid. Pyramidal IPSPs were abolished by a transection of the corticospinal tract in C2 but remained after a corresponding lesion in C5. After a C5 lesion pyramidal volleys facilitated transmission in the Ia inhibitory pathway with a time course suggesting disynaptic excitatory action on the Ia inhibitory interneurones. The trisynaptic pyramidal IPSPs were depressed by volleys in the appropriate recurrent motor axon collaterals as would be expected if these IPSPs were mediated by Ia inhibitory interneurones. It is concluded that trisynaptic cortico-motoneuronal inhibition is evoked by consecutive activation of propriospinal neurones in C3--C4 and segmental Ia inhibitory interneurones.


Studies of RNA metabolism in the nerve cells of hippocampus during training in rats. Direct evidence is presented that training to change behavior initiates synthesis of specific species of mRNA in pyramidal nerve cells of CA3 of the hippocampus in rats. Reversal of handedness was used as goal-directed operant test and active controls. Newly synthesized poly(A) associated mRNA with S value of 25 and a stimulation of poly(A) lacking mRNA of 8--9 S and 16--17 S were found in the CA3 nerve cells of trained but not in active controls.


Common projection of the motor cortex to the caudate nucleus and the cerebellum. 1. Stimulation of the caudate nucleus (Cd) was found to evoke early mossy fibre (MF) and late climbing fibre (CF) responses in fairly wide areas of the cerebellar cortex in cats. Points capable of eliciting the cerebellar responses were situated exclusively in the head portion of the nucleus. These responses showed a close resemblance to those induced by stimulation of the medial part of the anterior sigmoid gyrus (ASG) both in their contours and in their distributions. 2. There was a remarkable interaction between the Cd- and the medial ASG-induced field potentials in the pontine nuclei. When conditioned by the Cd stimulation at significantly short time intervals, the field potentials evoked by the medial ASG stimulation were more remarkably suppressed than those by the lateral ASG stimulation. 3. Field potentials or extracellular unitary activities in the inferior olive elicited by the Cd stimulation were closely related to those evoked by the medial ASG stimulation both in their responsiveness and in their topographical localizations. 4. When the cortical motor area had been ablated 10--14 days previously, the Cd stimulation elicited no responses in the cerebellar cortex. 5. From these findings, it was indicated that the Cd receives collaterals of the cortico-pontine and/or the cortico-olivary axons that originated almost exclusively from the neurones in the medial ASG (area 6). This suggested the existence of a common innervation of the basal ganglia and the cerebellar systems by the premotor area of the cerebral cortex.


Projections of the ascending somesthetic pathways to the cat superior colliculus visualized by the horseradish peroxidase technique. Projections of the somesthetic ascending pathways to the superior colliculus (SC) of the cat have been demonstrated by means of the horseradish peroxidase (HRP) tracing technique. Following HRP injection in one SC, marked neurons were found in the contralateral dorsal horn and in the contralateral dorsal column nuclei, mainly the cuneate nucleus. Moreover, in the contralateral trigeminal complex, the sub-nucleus caudalis of the spinal nucleus of the Vth nerve, and the subnucleus oralis plus the main sensory trigeminal nucleus were labeled. Thus, the anterolateral system and the lemniscal system subserving face and forelimb sensation send afferent fibers to the contralateral SC.


Functional organization in the cat's pulvinar complex. The responses of 192 single units in the cat's pulvinar-complex, comprising the inferior, medial and lateral pulvinar nuclei, were studied in paralysed cats, lightly anaesthetized with N2O/O2 supplemented with pentobarbitone. About 60% of the cells were visually driven and their receptive fields classified as either diffuse, concentric, movement sensitive, direction sensitive or orientation sensitive. The response fields of such cells were commonly large. Response field maps for the movement and direction sensitive cells formed a heterogenous population with uniform on-off fields to more complex arrangements with on- or off-centres, often with only partial surrounds; other cells responded exclusively to moving stimuli. A dual representation of the visual field was found in the pulvinar-complex corresponding to the striate and tectal recipient zones described anatomically by others. The representation in the striate recipient zone comprised an oblique column running medio-laterally and rostro-caudally through the inferior pulvinar and lateral margin of the medial pulvinar. The peripheral visual field was represented laterally and the vertical meridian medially; the upper visual field was represented dorso-laterally in the medial pulvinar and the lower visual field caudo-ventrally within the inferior pulvinar. That this visuotopic organization corresponded to the striate recipient zone was established by tracing the retrograde transport of HRP. Medial to the striate zone evidence for a second visual field representation was found, apparently more randomly organized than the striate zone, corresponding to the presumed tectal recipient zone. These results support the assertion that cytoarchitectural boundaries do not necessarily delineate functional (visuotopically organized) regions. These observations suggest caution when comparing cytoarchitecturally defined regions between species; rather, 'functionally equivalent' regions should be compared.


Selective degeneration of two out of the nine types of synapses in cat caudate nucleus after cortical lesions. In the cat caudate nucleus the same nine types of synapses are found as in putamen and fundus striati. The three parts of the striatum in the strict sense do not differ in the morphological differentiation of synapse types but only in their quantitative distribution. One-third of all synapses in the caudate nucleus are axo-spinous type IV synapses with a curved and divided asymmetric contact. This strongly suggests that the caudate nucleus interneuronal apparatus is dominated by centre-median input, in contrast to the putamen which is controlled by the cortico-striatal input to its internuncial cells and by its strong intrastriatal feedback mechanism. Extensive destruction of the convexity of the cortex and the medial cortex in one hemisphere results in dark degeneration of a large proportion of two of the nine types of caudate synapses: a) the axo-dendritic type VII synapses exciting the large spiny caudate neurons and b) the axo-spinous type III synapses making contact with the small spiny neurons of the interneuronal cell apparatus.


A ventral lateral geniculate nucleus projection to the dorsal thalamus and the midbrain in the cat. Retrograde tracing experiments using horseradish peroxidase (HRP) have been utilized for demonstrating the origin of efferent projections of the ventral lateral geniculate nucleus (LGNv) in the cat. HRP-positive cells identifiable as origins of thalamic projections were found in LGNv after injections of HRP into the lateral central intralaminar nucleus. The labeled cells appeared concentrated in the medial part of the internal division of LGNv, consisting of medium-sized multipolar cells. Contralaterally, fewer labeled cells were present in the corresponding part of LGNv. In the case of injections of HRP into the midbrain (pretectum and superior colliculus), labeled cells in LGNv were distributed almost exclusively in its external division, composed of mainly small cells. Little overlap of the distribution of HRP-positive cells was seen in LGNv between the thalamic and midbrain injection cases.


Afferent fiber connections from lower brain stem to hypothalamus studied by the horseradish peroxidase method with special reference to noradrenaline innervation. Attempts were made to determine the afferent projections to the anterior hypothalamus including the preoptic area from the lower brain stem by means of the horseradish peroxidase method combined with monoamine oxidase staining to identify noradrenaline (NA) neurons. In addition to this technique, a histofluorescence analysis was performed. NA fibers in the medial part of the anterior hypothalamus were mainly supplied by A1 and A2 NA neuron groups, while the lateral part and periventricular zone received NA terminals from both pontine and medulla oblongata NA neuron groups. Furthermore, the present study indicated that there were direct projections to the anterior hypothalamus from non-noradrenergic neurons in the lower brain stem: nuclei raphe dorsalis, centralis superior, cells in the mesencephalic and pontine central gray matter, nuclei parabrachialis lateralis and medialis, cells around fasciculus longitudinalis medialis.


Prostaglandin F2alpha distribution in pregnant rats. Studies on the placental transfer and distribution of 3H-PGF2alpha in rats on day 14 of gestation revealed that the isotope and/or its metabolites readily crossed the placenta. Notable levels of radioactivity were present in the embryos as well as in the placentas. The highest concentration of radioactivity was detected in the amniotic fluid. Maternal liver, kidney, and gut also showed significant uptake of the isotope.


Increased solubility of collagen. A biochemical defect in the experimental hydralizine-induced collagen disease-like syndrome. An increase of soluble fractions of collagen and a decrease of insoluble ones was found in the skin of guinea pigs with collagen disease-like syndrome, produced by prolonged treatment with hydralazine. Chromatography studies showed that the collagen alpha chains content in the skin increased and beta-chains decreased under conditions of the development of lupus-like syndrome. The obtained results suggested the inhibition of collagen maturation as one of biochemical defects of connective tissue in drug-induced collagen disease-like syndrome.


Distribution of monoamine oxidase in hippocampal region of the rat. The distribution and development of type A and type B monoamine oxidase (MAO) activities in the hippocampal region of the rat was investigated with biochemical microdetermination. Type A MAO is absolutely dominant and unevenly distributed in the hippocampus. The development of type A MAO in the hippocampus seems to be delayed and reachs adult levels by the 30th day after birth.


Absence of low molecular weight DNA polymerase activity from the nuclei of Amoeba discoides. Amoeba discoides nuclear protein partially purified by passage through Sephadex G-200 showed 3 high-mol.-wt. DNA polymerase activities which eluted in and just following the void volume. No low-mol.-wt (45,000 daltons) DNA polymerase beta activity was detected. Nuclear protein layered on 5--20% sucrose gradients also showed an absence of low-mol.-wt DNA polymerase beta. The void volume enzyme showed deoxyribonuclease activity, but no low-mol.-wt nuclease activity was detected.


The influence of ingested fluoride on the ascorbic acid concentration in guinea-pig tissues. Fluoride added to drinking water at concentrattions of 50 and 70 ppm provided highly significant increases in the ascorbic acid concentration in tissues but was without effect on the serum alkaline phosphatase and cholesterol.


Large scale isoelectric focusing analysis of the non-histone proteins of the nucleus: isolation of components with alkaline isoelectric points. After large scale isoelectric focusing of rat liver non-histone protein in polyacrylamide gel, pH range 4--8.6, the only protein material found outside the gradient was present in the cathode solution (20 mM NaOH). This was low mol. wt protein material (approximately 10,000) with an acidic amino acid composition. It bound 5--6 times its own weight of basic ampholine carrier ampholytes to give a complex with a pI of 8.82. This could be dissociated by dialysis against 1 M NaCl.


G-6PD loading of G-6PD-deficient erythrocytes. G-6PD-deficient erythrocytes were loaded during hypotonic hemolysis with G-6PD extracted from yeast. It was shown that enzyme was really trapped into red blood cells and remained functionally active.


Lipid composition of Microsporum gypseum. The lipid composition of Microsporum gypseum has been studied. The lipids amounted to 10.1% and phospholipids to 1.1% of the mycelial dry weight. Phosphatidyl choline, phosphatidyl serine and phosphatidyl ethanolamine were the major components, while lysophosphatidyl choline, and phosphatidyl inositol were present in smaller quantities. Neutral lipids consisted of monoglycerides, diglycerides, triglycerides, free and esterified cholesterol.


Nature of inhibition of rat testicular alkaline phosphatase by isatin. Isatin has been found to inhibit rat testicular alkaline phosphatase (EC 3.1.3.1). That the inhibition is non-competitive as well as non-allosteric is evident from a) the hyperbolic curve relating inhibition as a function of inhibitor concentration; b) the small change in enthalpy, free energy and entropy; c) the number of isatin molecules associating with 1 molecule of the enzyme (n=1.29); and, d) the decrease in the values of both Km and Vmax in the presence of isatin.


Effect of prenatal and neonatal pantothenic acid deficiency on rat intestinal phosphatases. Alkaline phosphatase activity was increased in the distal part of the small intestine of pantothenic acid deficient neonatal rats, while acid phosphatase activity was slightly increased and protein concentration was decreased throughout the small intestine. The growth and maturation of the distal part of the small intestine were retarded more severely than in the proximal part.


The effect of ligand on the kinetics of the sulfhydryl groups of human hemoglobin with p-mercuribenzoate. The rate of reaction of PMB with the masked sulfhydryls of human hemoglobin derivatives correlates well with the extent of dissociation for various ligands. It is suggested that the alpha1beta2 dimer of hemoglobin participates in the slow step of the reaction with PMB.


Electron microscopical evidence of the evolution of corynebacteria-like microorganisms within human erythrocytes. The corynebacteria-like microorganisms evoluting in the haemocultures take origin from electron dense granular bodies carried within the erythrocytes.


A mathematical analysis of the disk-sphere transition of the human red cell. By means of analytical calculations, an attempt is made to approximate the profile of the human red cell during the 'disk-sphere' transition induced by variation of the tonicity of the medium.


Chain-proteins of the vertebrate lens.

Chain-proteins of the vertebrate lens. Some lens proteins exist in a chain-like form in the vertebrate lens fibre cells. They consist of globular proteins arranged on a filamentous backbone.


Antimicrobial activity of metal derivatives of sulfonamides. Antimicorbial activities of a series of metal derivatives of some sulfa drugs were examined. Such metal derivatives showed higher antimicorbial activity than the parent sulfa drugs, and among the metals, gold derivatives are seen to be the most effective.


Identification of Trypanosoma theileri as a contaminant in primary cultures of bovine retina. T. theileri has been isolated from primary cultures of bovine retina and subcultered successfully for 2 passages in sub-confluent cultures. When cultures reached confluency no trypomastigotes or epimastigotes could be detected and attempts to recover trypanosomes from these cultures were unsuccessful. The presence of intracellular forms could not formally be excluded.


Focal brain hyperthermia. I. The cerebellar cortex. Focal brain hyperthermic methodology has been described and data presented on the cerebellum which show that enhancement of electrical activity of cerebellar cortex occurs when this method is used with careful monitoring of temperature. The duration of electrically induced cerebral after-discharges is shortened when cerebellar warming reaches 39.5--42.0 degrees C,. Since these effects are repeatable over many hours, there appears to be little, if any, resultant damage. Such induced changes in the cerebrum resemble those previously reported in which electrical stimuli were applied to the cerebellar cortex.


Sex related fibrinolytic activity in rat tissues. Histochemical study of many organs of male and female adult Wistar rats of the same age showed no difference in fibrinolytic activity (plasminogen activator activity) between the sexes.


Variation in the lactase dehydrogenase activity of the esophagus. Quantitative assay and electrophoretic study of lactate dehydrogenase (LDH) from various tissues of the opossum esophagus were performed. On the basis of expression of the LDH isozymes, we concluded that the smooth muscle of the body of the esophagus carry on more anaerobic glycolysis than the striated muscle. The smooth muscle of the gastroesophageal junction carry on both anaerobic as well aerobic glycolysis.


Ultrastructural correlation of water reabsorption in isolated rat cauda epididymidis. Electron microscopic study was made on the water reabsorption of the epithelial cells of the rat cauda epididymidis. It was shown that when the epididymal duct was reabsorbing water at a maximal rate, widely dilated intercellular spaces were seen. It is suggested that the standing gradient model of water reabsorption first proposed for the gall bladder may also operate in the cauda epididymidis.


The effect of adrenaline on the electrogenic Na+ pump in cardiac muscle cells. Electrogenic Na+ pump currents during K+-activated hyperpolarizations of bullfrog atrium muscle fibres are increased by adrenaline. The log dose-response relation between these currents and activating K+ concentrations is expressed by a sigmoidal curve, which is shifted in parallel to the left by adrenaline. It is suggested that adrenaline increases the rate of Na+ extrusion without increasing the Na/K coupling ratio and total number of pumping sites.


Inhibition of new blood vessel formation in mice by systemic administration of human rib cartilage extract. 1 M HCl-guanidine extract of human funnel chest rib cartilage administered i.v. to mice decreased specifically vasoproliferation induced by intradermal injection of allogeneic murine lymphocytes.


Fibrosing alveolitis (pulmonary interstitial fibrosis) evoked by experiemntal inhalation of Gasoline vapours. Rats exposed to an atmosphere contaminated with gasoline vapour for 6--12 weeks exhibit progressive focal interstitial fibrosis of the lung, which is associated with irregular alveolar collapse. It is suggested that this experimental model of diffuse fibrosing lung disease constitutes a useful tool for the study of the dynamics of pulmonary reactivity to atmospheric pollutants and which may facilitate an understanding of the pathogenesis of fibrosing alveolitis in man.


GLC determination of betahistine in serum. A gas chromatographic method was developed for the determination of betahistine in serum in the range of 0.6-6.0 microgram/ml.


Isolation of the major toxic protein from the skin venom of the crested newt, Triturus cristatus. A new protein, of molecular weight 160,000, was isolated from the skin venom of the crested newt and partially characterized by bioassays and biochemical methods. This protein shows the same functional properties as the crude venom, which produces convulsions in mice and is cytotoxic.


Effect of theophylline on myocardial adenylate cyclase activity. Theophylline (0.001-10.0 mM) did not increase but rather decrased adenylate cyclase activity (AC) of guinea-pig auricles. Isoprenaline (1-100 microgram) and sodium fluoride (0.3-10.0 mM) stimulated AC in a concentration-dependent manner.


Changes of profiles of neutrophil granulocytes induced with the administration of L-DOPA and prednisolone. Morphological changes of granulocytes following combined treatment with L-DOPA and prednisolone were elucidated at the electron microscopic level. Neutrophil granulocytes exhibited marked changes in their surface as evidenced by scanning electron microscope. It is suggested that neutrophil granulocytes are sensitive to some biogenic amines.


Further studies on the effect of red and far red light on rat retinal development. The influence on the development of the outer segments of the rat retina of far red and red light in different sequences was investigated. The far red treatment appeared to be dominating, and for animals treated with far red light first, further treatment of red light could not bring the outer segment growth back to normal. The treatments also initiated different dopamine uptakes in the retinas.


Formation of intracellular canaliculi in reaggregated striated duct cells of rat submandibular gland during short-term stationary culture. Reaggregated striated duct cells of rat submandibular gland formed deep tubular invaginations of the cell membrane, i.e. intracellular canaliculi, which are not present in the original tissue, after 24 h of the stationary culture.


Isolation of histone proteins from rat normal and tumour blood plasma. Histone proteins were isolated from both normal and tumour rat blood plasma: H1, (H2b + H2a) for normal plasma and H1, H3, (H2b + H2a) and H4 for tumour one.


Effect of papain on experimental amyloidosis. Experimental amyloidosis was induced in mice by repeated injections of complete Freund's adjuvant (CFA) reinforced with a bacterial vaccine. Papain was administered i.p. at various time intervals during the treatment with CFA. Amyloidosis was found only in the spleen and the liver. No statistically significant differences were found between the papain-treated and the control groups. It is assumed that, although papain releaseed the polysaccharide moiety from the polysaccharide protein complex, the released polysaccharides were most probably bound by electrostatic forces to the amyloid fibres, and did not interfere with amyloidogenesis.


Human adenosine deaminase and chromosome 20. In patients exhibiting in marrow cells deletion of the long arm of chromosome 20, the specific activities of adenosine deaminase in cells of the peripheral blood are normal. This suggests that the gene for adenosine deaminase is not localized to the distal segment of the long arm of this chromosome.


Stimulation of methemoglobin reduction by selenium: a comparative study with erythrocytes of various animals. The extent of stimulation of methemoglobin (metHb) reduction by selenite depends upon the level of reduced glutathione (GSH) in the erythrocytes. The reason for the species difference in the effect of selenite was discussed with respect to species differences in the GSH levels in erythrocytes.


Plasma vasoactive intestinal polypeptide (VIP) levels and intestinal ischaemia. Vasoactive intestinal polypeptide (VIP) is released into the portal circulation in large quantities by ischaemic bowel. In view of its known high concentration in the gut and potent vasoactive properties it may well be implicated in the pathogenesis of the serious haemodynamic changes produced by gut ischaemia.


A dialysis rate method for the measurement of free iodothyronine and steroid hormones in blood. From the dialysis rate of a small amount of tracer hormone from a serum sample through a semipermeable membrane towards an identical serum sample, the free hormone fraction can be calculated. This method is free from a number of artefacts that may occur in equilibrium dialysis.


Inhibition of testicular androgenesis by urinary gonadotropin-inhibiting substances in rats. The effect of urinary gonadotropin-inhibiting substances (GIS) on the androgen synthesis in rat testes was studied in vitro and in vivo. GIS, which was added to the incubation medium containing tesased testicular tissues and injected into rats for 2 days, showed a suppressive effect on the formation of androstenedione from pregnenolone in the testis.


Action potentials in non-tumor cells from the anterior pituitary gland. Non-tumor cells of rat anterior pituitary gland are able, upon electrical stimulation, to generate action potentials which are based on an increase of the membrane permeability to both Na+ and Ca2+.


Activity alterations of metabolic enzymes in the anterior pituitary of female rats during acute and chronic starvation, as well as after refeeding. The activity of glycolysis and hexose monophosphate shunt decreases while the activity of some oxydative enzymes and acid phosphatase increases in the anterior pituitary of adult female rats during starvation. The alterations depend on the severity of starvation. The polypeptide hormone production also decreases. A close relationship exists between the metabolic activity of the gland and its endocrine function.


A simple system of multiple organ-baths. A compact and easily assembled system of multiple organ-baths is described , in which use is made of readily available materials.


National nutrition surveillance.

National nutrition surveillance. National Nutrition Surveillance includes nutritional assessment surveys to ascertain the extent of malnutrition in populations, to identify possible causes, to establish baseline data for monitoring nutrition, and to select mechanisms for nutrition surveillance (in a restricted sense). An example of the results from a recent nutritional assessment survey in the United States is the negative association of obesity with energy intake, exercise and socioeconomic status, which has implications for public nutritional policy. Nutritional monitoring measures changes in population nutrition over time. An example of the results from nutritional monitoring is the unexpected and presently unexplained decrease in serum cholesterol levels of middle-aged women in the United States over the past decade. Nutritional surveillance in the restricted sense not only identifies malnutrition but is administratively organized to intervene rapidly. National Nutrition Surveillance depends on metabolic and clinical research to decide on its priorities. This research indicates that malnutrition involves more than under-nutrition, and greater emphasis should be given in National Nutrition Surveillance to this wider context of malnutrition. These results will in turn help set priorities for basic and applied research in nutrition. It is important that the research community participate in the review presently under way of the role of the National Center for Health Statistics in National Nutrition Surveillance.


Neural control of renal tubular sodium reabsorption of the dog. The evidence supporting a role for direct neurogenic control of renal tubular sodium reabsorption is reviewed. Electron microscopic and fluorescence histochemical studies demonstrate adrenergic nerve terminals in direct contact with basement membranes of mammalian renal tubular epithelial cells. Low level direct or baroreceptor reflex stimulation of renal sympathetic nerves produces an increase in renal tubular sodium reabsorption without alterations in glomerular filtration rate, renal blood flow, or intrarenal distribution of blood flow. The antinatriuresis is prevented by prior treatment of the kidney with guanethidine or phenoxybenzamine. Possible indirect mediation of the antinatriuresis by other humoral agents known to be released from the kidney upon renal nerve stimulation (angiotensin II, prostaglandin) was excluded by experiments with appropriate blocking agents. Reflex diminutions in renal nerve activity (left atrial distention, stellate ganglion stimulation) produce a decrease in renal tubular sodium reabsorption independent of glomerular filtration rate or renal blood flow. The anatomically described adrenergic innervation of the renal tubules participates in the direct regulation of renal tubular sodium reabsorption.


Postruminal digestion and absorption of nitrogenous components. Digesta containing microbial protein, undegraded (bypass) feed protein, some free amino acids and oligopeptides, and microbial nucleic acids passes from the rumen-reticulum through the omasum to the lower gut (abomasum and small intestine). The rate of neutralization of abomasal digesta flow is slower in ruminants than in nonruminants, and activation and peak activity of the pancreatic proteases is delayed to the mid jejunum. The overall apparent digestibility in the small intestine of proteins and microbial or exogenous nuclei acids is 60-70% and 75-85% respectively. Absorption mechanisms in ruminants for protein and nucleic acid digestion end products appear similar to those described in nonruminants, but the highest rate of amino acid uptake was found in the mid to lower ileum. Essential amino acids (Met, THr, Val, Ile, Leu, Phe, Lys, His, Arg) are absorbed faster than nonessential amino acids (Gly, Glu, Asp, Ser, Pro, Cys, Tyr). After feeding, plasma amino acids remain unchanged or decline in a mature ruminant, while in nursing lambs, plasma free amino acids levels increase after a meal.


Delayed onset of luteinization as a cause of infertility. Two groups of infertility patients with regular cycles and apparently normal ovarian function were studied. In group I (n = 28) the infertility could be explained satisfactorily either by tubal occlusion or by infertility of the husband, or the women became pregnant within a few months. In group II (n = 32) no explanation was found for the infertility. Significantly fewer ovulation stigmata were present at laparoscopy in group II than in group I (P less than 0.05). In group I the basal body temperature (BBT) (P less than 0.001) and the plasma progesterone concentrations (P less than 0.05) were significantly elevated on the 1st day following the luteinizing hormone (LH) peak. In group II, THE BBT was slightly elevated on the 1st day following the LH peak (P less than 0.05), but the increase in the plasma progesterone concentrations occurred only on the 2nd day following the LH peak. In four women the onset of the BBT rise followed a normal LH peak with delays respectively, of 3, 4, 4, and 5 days, and in two women no LH peak occurred immediately prior to the onset of the BBT rise. The datings of the endometrial biopsies in these patients were in phase with the onset of the BBT rise but not with the LH peak. It is concluded that anovulation with in situ luteinization may be a rather frequent cause of infertility in regularly cycling women. A hypothesis about the mechanism of anovulation with in situ luteinization is proposed.


Clinical investigation of the menstrual cycle. II. Neuroendocrine investigation and therapy of the inadequate luteal phase. Nonhormonal drugs--diphenylhydantoin and nialamide, which act on the central nervous system and have no known endocrine activity--were given to two groups of women with distinct types of electroencephalographic patterns in an effort to regulate menstrual disorders. Equalization of the lengths of both the follicular phase and the luteal phase to the normal range was observed during the drug therapy. Forty-five per cent of the pregnancy rate was achieved in 36 of the 80 infecund patients within 4 months of treatment. The mode of action of these drugs is still unknown.


Prolactin-secreting pituitary microadenoma: detection and evaluation. Eleven women with secondary amenorrhea associated with hyperprolactinemia were studied. Base line evaluations, visual field determinations, and routine sella turcica x-rays were normal. Prolactin-secreting pituitary microadenomas were found in all of the patients only after further diagnostic studies were carried out. These studies included polytomography of the sella turcica; dynamic pituitary testing of growth hormone reserve, adrenocorticotropic hormone reserve, and gonadotropin reserve; and prolactin suppression with L-dopa. The early diagnosis of a small prolactin-secreting adenoma may be possible if several diagnostic criteria are utilized. The most sensitive diagnostic indices available are (1) polytomography, (2) the magnitude of the plasma prolactin elevation, and (3) the failure to suppress prolactin secretion with L-dopa. Our findings emphasize the importance of an extensive evaluation of all women with amenorrhea associated with hyperprolactinemia.


Comparison of plasma hormone changes using a "conventional" and a "paper" pill formulation of a low-dose oral contraceptive. Two formulations of a low-dose oral contraceptive (Microgynon: 150 microgram of levonorgestrel [NG] +30 micrograms of ethynylestradiol [EE2]) were studied. The first was the "conventional" pill; the second was a "paper" pill prepared by evaporation of aliquots of a solution of the component steroids onto squares of edible cellulose separated by perforations, similar to a sheet of postage stamps. The effects of the two formulations on plasma levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17beta-estradiol (E2), and progesterone were compared. Samples of blood were obtained from five women during a treatment period on the "conventional" pill and from five on the "paper" pill. When possible, blood samples were also obtained from a "control" cycle of each of these female subjects. Plasma LH, FSH, E2, and progesterone levels were determined by specific radioimmunoassay methods during control and treatment periods and NG and EE2 levels during treatment periods. Eight-hour plasma profiles for NG and EE2 at the beginning and in the later stage of the treatment periods were obtained and these samples were also analyzed for LH, FSH, E2, and progesterone. Results showed that with one exceptcrogynon were equally effective in suppressing ovulation. As in a previous study, FSH levels appeared to be one of the most sensitive indices of suppression.


Further developed device for human sperm freezing by the twenty-minute method. A further developed, practical device for human sperm freezing is described by which the preparation of sperm and the freezing process are reduced to a simple procedure requiring about 20 minutes. The instrument is based on the principle of evaporation of liquid nitrogen, which acts as a refrigerant for the freezing plate under the control of a thermostat. Rapid-rate freezing can be performed for pellet production and slow-rat freezing for paillettes; a high degree of isolation of samples is maintained by easily interchangeable freezing plates. Typical stages of freezing are accomplished at temperatures of +5 degrees C and--80 degrees C, with storage at--196 degrees C. The recovery index is 50% to 70%. The treatment was applied to 56 patients, resulting in 19 normal deliveries, 3 abortions, and 9 current pregnancies.


Immune infertility and new approaches to treatment. A number of patients who have involuntary infertility show sperm antibodies in the blood serum, as detected by two quite different methods of spermagglutination. These techniques are the Kibrick method (gelatin agglutination test) and the F-D method (tube-slide agglutination test). By the former technique, the sera of 18% of women and 9% of men from infertile couples were found to be positive; by the latter technique, the sera of 15% of women and 5% of men were positive. Such cases are termed "immunologic infertility." In an effort to develop new methods for the treatment of infertility, two procedures were explored. One is a sperm washing insemination method in which fresh semen from a man with the antibody is centrifuged, resuspended in an albumin solution, and then used for insemination. The second is an immunosuppression method, using methylprednisolone at a dose of 96 mg/day for 7 days. A striking decrease in antibody level was seen in some cases, with ensuing pregnancy. The success rates for these methods have been of the order of 14% to 22%.


Effects of vasectomy and antisperm antibodies on human seminal fluid deoxyribonucleic acid polymerase activity. DNA-synthesizing complexes possessing a sucrose buoyant density of 1.24 to 1.25 gm/ml were identified in cell-free human seminal fluids prior to and 1 to 3 months following division of the vasa deferentia, performed for fertility control in otherwise normal males. After vasectomy, there was a 3.5-fold decrease in endogenous DNA polymerase activity per ejaculate. Partial purification of the seminal fluid DNA polymerase by gel filtration revealed a similar 3.5-fold decrease in dT12--18-poly (rA)-templated DNA polymerase activity postvasectomy. Immunoglobulin G, isolated from a rabbit immunized with nuclei derived from detergent-treated ejaculated human spermatozoa, inhibited both sperm- and seminal fluid-derived DNA polymerase activity. The decrease in seminal fluid enzyme activity following vasectomy might be due to its inhibition by sperm autoantibodies induced after vas division.


Hormonal effects of an antiestrogen, tamoxifen, in normal and oligospermic men. The administration of tamoxifen, 20 mg/day for 10 days, to normal males produced a moderate increase in luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and estradiol levels, comparable to the effect of 150 mg of clomiphene citrate (Clomid). However, whereas Clomid produced a decrease in the LH response to LH-releasing hormone (LHRH), no such effect was seen after the administration of tamoxifen. In fact, prolonged treatment (6 weeks) with tamoxifen significantly increased the LH response to LHRL. Treatment of patients with "idiopathic" oligospermia for 6 to 9 months resulted in a significant increase in gonadotropin, testosterone, and estradiol levels. A significant increase in sperm density was observed only in subjects with oligospermia below 20 X 10(6)/ml and normal basal FSH levels. When basal FSH levels were increased or oligospermia was moderate (greater than 20 X 10(6)/ml); no effect on sperm density was seen. As sperm density increased, FSH levels decreased, suggesting an inhibin effect. Sperm motility was not improved by tamoxifen treatment. In five boys with delayed puberty, tamoxifen treatment appeared to activate the pituitary-gonadal axis and pubertal development.


Further investigations on the maturation and degeneration of human ovarian follicles and their oocytes. Human ovarian follicles showed activity of alkaline phosphatase, acid phosphatase (AcP) leucine aminopeptidase, and lactate dehydrogenase (LDH) in the theca interna. The granulosa of nonovulatory tertiary follicles showed moderate activity, whereas that of preovulatory Graafian follicles showed strong activity of LDH and AcP. The activity of these enzymes in the follicular fluid was measured. In nonovulatory tertiary follicles, activity of 3beta-ol-steroid dehydrogenase (3beta-OHSD) was found only in the theca interna; their fluid contained 290 ng/ml of progesterone and 502 ng/ml of 17beta-estradiol (average). Preovulatory Graafian follicles showed activity of 3beta-OHSD in the theca as well as in the granulosa. The progesterone concentration of the fluid was 7037 ng/ml and the 17beta-estradiol concentration was 2800 ng/ml (average). More oocytes could be aspirated from ovaries of younger women than from those of older women. In both age groups one out of three oocytes was degenerated. Oocytes with preovulatory changes were found only in follicles with preovulatory changes in their walls. Degenerated oocytes were found in some nonovulatory follicles as well as in some follicles with preovulatory changes in their walls.


Binovular follicles in the adult human ovary. The human ovary may contain binovular or polyovular follicles at birth, but they are unusual later in life. Binbovular follicles were found in bilateral ovarian biopsies from a patient with primary amenorrhea who had been treated with exogenous gonadotropins. The fine structural morphology of these follicles has shown that both oocytes were in the resting meiotic prophase, that their respective vitelline bodies faced each other across the intervening plasma membranes, and that the adjacent oocytes made mutual contacts similar to those found between granulosa cells and oocytes. From the appearance of the multivesicular bodies in nearby stromal fibroblasts it is suggested that these follicles had formed by fusion of two adjacent primordial follicles by a mechanism similar to the depolymerization of the ground substance in the apex of the Graafian follicle that leads to ovulation.


The effect of ligation or separation between the intrauterine device horn and adjacent ovary on implantation in the hamster. The purpose of this study was to determine whether the luteolytic action of an intrauterine device (IUD) is suppressed following interruption of the continuity between the IUD uterine horn and the adjacent ovary. After several estrous cycles, a silk IUD was placed in the cervical end of one uterine horn of adult hamsters. The animals were then mated, and on day 6 of gestation the ovary and oviduct contralateral to the IUD were removed and a ligature was placed between the IUD horn and the adjacent ovary. The hamsters were killed on day 9 or day 13 of gestation. Fetal development in the contralateral horn was suppressed on day 13 but not on day 9. In the second study the animals were treated as in the first study except that the communication between the IUD horn and the adjacent ovary was severed completely. The hamsters were killed on day 9 or day 13. On both days 9 and 13 normal fetal development was observed in the control horn; no implantation sites were present in the IUD side. In the control (non-IUD) animals of each study, normal fetuses were present in both uterine horns. The study demonstrates that luteolysis does not occur if there is complete disruption of the communication between the IUD horn and ovary. The study also demonstrates that, since implantation did not occur in the IUD horn with a normally functioning ipsilateral ovary, the luteolytic action of the device is not the prime factor in suppressing implantation in the hamster.


Changes in the structure and function of the testes and epididymides in vasectomized rams. Vasectomized rams were studied with regard to the structure and function of their testes and epididymides at different periods up to 3 years and 9 months after the operation, and compared with intact control rams. Control rams showed a marked seasonal pattern with higher values for size and weight of testes, diameter of seminiferous tubules, Sertoli cell ratios for germ cells, and size of cauda epididymidis immediately prior to and during the breeding season than at other times of the year. In vasectomized animals the seasonal pattern was ill-defined, the testicular parameters were lower, and the cauda epididymidis was larger than in intact rams. Spermatogenesis was qualitatively and quantitatively affected after vasectomy, with a sequential ebb-and-flow pattern of spermatogenic arrest and hypospermatogenesis. Epididymal changes included the development of multiple spermatoceles surrounded by a granulomatous reaction, and disturbances in the process of sperm maturation.


Conception following insemination with a freeze-preserved retrograde ejaculate. Retrograde ejaculation, an infrequent cause of male infertility, may be the sequela of prostate or bladder neck surgery or the result of interruption in the sympathetic innervation to the bladder neck. The diagnosis is established by history and examination of the urine. In infertile couples artificial insemination homologous (AIH) using retrograde ejaculate recovered from the bladder has been successfully accomplished, but conception has occurred only in isolated cases. A literature review of the subject is presented. The technique of semen recovery from the bladder is time-consuming and uncomfortable to the patient, while the quality of the semen recovered is variable and the risk of iatrogenic urinary tract infection is increased. To avoid the above problems, and to have sperm available for AIH at the time of induced ovulation in an anovulatory wife, we were able to freeze-preserve ejaculate recovered from the bladder for future use. A case of conception following AIH with freeze-preserved retrograde ejaculate is presented.


[Reactions of the neurons of midbrain and diencephalic structures during perception of acoustic signals and induced vocalization]. 75% of the chick mesencephalic and diencephalic neurons changed their activity both on perception of acoustic stimuli (noise, frequencu-modulated tone, ecological stimuli) and at the emission of sound. The data obtained suggest that structures of the chick mesencephalon and diencephalon are involved in vocal reactions and have sound-sensitive neurons processing the acoustic information. The diencephalic neurons were found to have a higher specificity as compared with the mesencephalic cells.


[Electromyotopography of 2-joint muscles of the thigh in rats subsequent to changes in their structure due to congenital skeletal deformity]. With the aid of multi--point recording of focal APs in the muscles, the bringing together of the motor nervous terminals and the increase in their dispersion within each terminal area as observed in the rat femoral two-joint muscles at inherent deformity of the hindlimbs, were revealed to induce a change in the character of interference of the focal APs. At the supramaximal stimulation of a respective ventral root of the spinal cord, the areas of motor nervous terminals having been brought together, an increase of the mutual effects of APs of adjacent areas' muscular fibers occurs as well as alteration of the character of AP conduction in the muscle which seems to be due to the interaction between external loops of muscular APs. The data obtained show the advantages of the electromyotopography which enables to estimate not only the character of AP spreading within the muscle but the latter's structure too (the length of muscle fibers, situation of motor nervous terminals, etc.).


[Hemodynamic changes upon nociceptive stimulation and stimulation of the amygdaloid complex following catecholamine administration]. In cats, changes in arterial pressure (AP), intracardiac pressure (ICP), and blood flow volume rate following a nociceptive stimulus, stimulation of the amygdala and the combination of these before and after adrenaline (A) and norepinephrine (NE) administration into the lateral nucleus of amygdala, were studied. Nociceptive stimuli and electric stimulation of amygdala increased AP and ICP. The combination of these increased the pressor reaction. The blood flow volume rate was not altered by the nociceptive stimulus while decreasing at amygdalar stimulation. After A and NE administration the stimulation of amygdala plus the nociceptive stimulus suppressed the pressor reaction; a nociceptive stimulus was followed by the same changes as in intact cats; a nociceptive stimulus plus the stimulation of the amygdala increased the pressor reaction. The blood flow volume rate response to the stimuli was the same as in the control group. But the stimulation of amygdala after NE and a nociceptive stimulus plus amygdala stimulation (20 min after A) increased the blood flow volume rate, while the stimulation of amygdala alone with A administration reduced the blood flow.


[Electrocardiographic findings in normal dogs]. Electrocardiographic findings were obtained in 70 unanesthetized dogs after their adaptation to environment and to forced position on the right side of the body. The Q wave was recorded in more than half of the animals in the standard leads and was absent in the chest those. The T wave was more often negative in the standard leads and positive in the chest ones. The ECG of each dog kept its individual features during the whole period of observation. The data obtained suggest the necessity of using chest leads apart from the standard ones.


[Background and evoked neuronal activity of ganglia in the submucous plexus of the small intestine]. In preparations of the cat small intestine, presence of three types of cells was revealed: 1st--with single spikes, 2nd--with slow, and 3rd--with fast bursts of spontaneous activity as well as groups of silent neurons. The 1st and the 2nd type cells and some silent cells receive activating influence from adjacent ganglia. Silent neurons included mechanosensitive cells responding with specific series of discharges to mechanical deformation of the ganglion and to electric stimulation of adjacent ganglia. The interneuronal relationships within the ganglion and connections between cells of adjacent ganglia were revealed which suggests that all neurons of the plexus are involved in a functional network.


[Amplification factor in the thermoregulatory system at different environmental temperatures]. With the aid of a heater implanted into the hypothalamus, the temperature was raised in the medial preoptic area of the rabbit hypothalamus; Vasodilatation was observed at that in the helix and in the nose skin. The heat emanated during this response was measured with the aid of a dynamic biocalorimeter. The amplification coefficient in the thermoregulation system was calculated as the ratio: the heat emanated by the rabbit during the vascular thermoregulatory response--the heat introduced into the hypothalamus in the course of heating. At the temperature 20% in the calorimeter chamber, the amplification coefficient was 3.9+/-0.8, and at 24 degrees it was as high as 13.6+/-1.0.


[Distribution of water between the extracellular and intracellular space in rats]. In anesthetized rats the renal pedicules were clamped and the solution with THO, antipyrine, thyocyanate, inulin, 22Na, 36Cl, 82Br was injected into the tail artery. The space of distribution of THO was 65.1% body weight, antipyrine--81.9%. The volumes of distribution of 22Na (27.4%) and thyocyanate (26.9%) were higher than the 36Cl (24.8%) and 82Br (25.6%) spaces. Inulin space was 13.8%. There was no difference between the volume of distribution of the substances in female and male rats. The same spaces of the substances (except inulin) were determined in rats with intact kidneys. After i.a. administration of 5 ml/100 g body weight of Ringer's solution the recovery of all the substances was about 100%. The data obtained indicate that antipyrine cannot be used for estimation of the total body water in rats. For the measurement of extracellular fluid it is better to use radioisotopes 82Br, 36Cl or 22Na; more variable data were observed with thyocyanate and inulin.


[Varations between strains in the concentration of RNA in the cerebral cortex of rats differing in their capacity for learning]. Concentration of RNA in the brain cortex was investigated in two strains the rats Wistar and Krushinsky--Molodkina. It is found that K--M rats, which have higher speed of learning possess higher concentration RNA in the cortex brain than rats of Wistar strain. Conditional reflectory training of rats induced increase of RNA concentration in the brain cortex experimental rats when it is compared with control groups of rats. It is suggested that there is not only an ontogenetic, but also a genetic correlation between the level of RNA the brain cortex and a capability the rats to the learning.


A multicentered study of lysine therapy in Herpes simplex infection. Lysine appears to suppress the clinical manifestations of herpesvirus infection. 45 patients with frequently recurring herpes infection were given 312-1,200 mg of lysine daily in single or multiple doses. The clinical results demonstrated a beneficial effect from supplementary lysine in accelerating recovery from herpes simplex infection and suppressing recurrence. Tissue culture studies have demonstrated an enhancing effect on viral replication when the amino acid ratio of arginine to lysine favors arginine. The opposite, preponderance of lysine to arginine, suppresses viral replication and inhibits cytopathogenicity of herpes simplex virus. The codons characterizing herpes simplex DNA apparently specify production of viral capsids at the expense of host cell histones.


Acquired hypertrichosis lanuginosa.

Acquired hypertrichosis lanuginosa. Acquired hypertrichosis lanuginosa occurred in a man with lung cancer. Fine lanugo-like hair covered his face, trunk, and extremities, and there were marked pigmentation of oral mucous membrane and a painful red tongue. Our study revealed a high concentration of carcinoembryonic antigen (CEA) in the serum of the patient. We considered that CEA might be an important etiological factor of this disease.


Woringer-Kolopp disease: pagetoid reticulosis. A typical clinical and histologic case of so-called 'pagetoid reticulosis' or Woringer-Kolopp disease is reported. This is a chronic cutaneous condition usually with a single focus or at most with a few patches confined to a circumscribed region. A disseminated form has been described as Dupont-Vandaele type, but its relationship to the classic Woringer-Kolopp disease is uncertain. The nosological location of pagetoid reticulosis has not been established, but there are reasons to regard it as a particular and well-defined entity. In relation to the nature of this condition and to the origin of the 'pagetoid cells', it is tempting to consider the possibility that Woringer-Kolopp disease might be a lymphoproliferative epidermotropic disorder, classifiable as a benign form of 'cutaneous T-cell lymphoma', but the early histologic changes are rather indicative of an epidermal origin.


Angiokeratoma of vulva.

Angiokeratoma of vulva. A female of 66 who presented with long-standing pruritus vulvae showed angiokeratoma of the vulva as an incidental finding. This benign tumour is uncommon and in a survey of 150 patients over 50 years old (mean age 76.9), no further example was found.


2-chloroethanol--percutaneous toxicity of a solvent. This report is a part of a comparative study where skin pathology, blood concentrations and percutaneous toxicity after epicutaneous administration of solvents are investigated. The method used for the study of percutaneous toxicity proved capable of differentiating between different applied amounts of 2-chloroethanol. This solvent was found to be highly toxic, even 0.10 ml killed all 20 exposed animals within 24 h. A 35% aqueous solution killed about half of the animals, while a 10% solution killed only 1 out of 20. A comparative study with intraperitoneal administration of the same amounts as epicutaneously, showed that the mortality and mean time until death diminished with rising amounts (with only one exception).


Quantitation of ultrastructural changes in mouse pancreatic acinar cells caused by foreign serum. Quantitative changes in the pancreatic acinar cell organelles were studied in BALB/c mice injected with 1.0 ml fresh rabbit serum intraperitoneally. Groups of 5 mice were killed at 0, 1, 3, 6 and 12 h after the serum injection. Pancreatic tissue was processed for electron microscopy by glutaraldehyde and osmium tetroxide fixation and Epon embedding. The proportions of acinar cell cytoplasm (volume fractions) occupied by zymogen granules, granular endoplasmic reticulum, Golgi apparatus, mitochondria and lysosomes (including autophagosomes) were determined by the point counting method from electron micrographs. The volume fraction of lysosomes increased during the first 3 h and remained markedly elevated up to 12 h. The volume fractions of zymogen granules increased from 12 to 28% in 12 h. It was concluded that the secretory mechanism of pancreatic acinar cells was injured by the foreign serum. The injury caused accumulation of zymogen granules and increased autophagic activity in the acinar cells.


Filaments in astrocytes and axons of mice optic nerve. A freeze-etching study. Fixed and nonfixed tissues from optic nerves of 20-day-old mice were examined with the electron microscope using the freeze-etching method. In this study the filaments of fibrious astrocytes are compared with those of axons. Both the astrocytic perikaron and the processes show a characteristic aspect in view of the arrangement and density of filaments. The most reliable criterion to distinguish them from nonmyelinated axons is the presence of areas with packed filaments. Furthermore, we demonstrated morphometrically that the filaments of axons and astrocytes from prefixed specimens had a statistically significant (p less than 0.001) smaller diameter (9.5 +/- 0.3 nm) than those from nonprefixed ones (10.5 +/- 0.3 nm). The diameters of filaments in axons and astrocytes are identical in fixed as well as in nonfixed material. The fine structure of filaments displays in addition to a helical form also a certain periodicity.


Establishment and characterization of a cell line derived from human colon adenocarcinoma (HuCCL-14). A continuous human colon carcinoma cell line (HuCCL-14) was established whose cells possess an epithelial-like morphology and are capable of growing in soft agar and on monolayers of normal cells. HuCCL-14 cells yielded high levels of carcinoembryonic antigen, and the analysis of their chromosomal constitution revealed a mode of 70 chromosomes per cell. HuCCL-14 cells produce malignant tumors when injected into nude mice. Preliminary virologic studies indicate the release of RNA particles having a density of 1.15--1.19 g/ml.


Selective effect of fractions of a yeast extract (PCO) on normal and malignant cells. The selective action of two fractions of PCO (a yeast extract) on normal and malignant cells was demonstrated. In vivo, the mitotic activity of malignant cells was inhibited by the methanol-insoluble fraction of PCO, whereas the methanol-soluble fraction caused no inhibition. The in vitro studies, however, showed inhibition of mitoses with both fractions. The malignant cells employed in vitro and in vivo were the Krebs-2 and Ehrlich carcinomas. The nonneoplastic cells tested in vitro were established cultures of epithelial-like cells from murine bone marrow and thymus, and corneal epithelium and peripheral blood in vivo.


Dependence of cell-mediated immune lysis of the EL-4 ascitic lymphoma on its population composition and rhythm. Investigations on cell-mediated immune release of 51Cr from the EL-4 ascitic lymphoma showed that daily rhythmic changes can be correlated with the dominance of certain cell types in the population. Cells in compartment 1--i.e., those representing true G0, early G1, S and M--are most sensitive to effector cell attack. During the establishment 96-hour appearance cycle of the population, each day a different compartment will predominate, with corresponding variations in percent immune release. On days when spontaneous 51Cr release shows a maximum, immune release is minimal. The differences between maximal values of immune release may reach more than 300%, when findings from different days in the appearance cycle are compared.


Ontogeny of two-way avoidance in male and female rats. In Experiment I, 17-, 21-, 36-, 51-, 90-, and 200-day-old male and female rats were given a single session of 100 two-way avoidance (TWA) trials. In the 2nd experiment, males and females of these ages and 15 and 28 days of age that were obtained from a different source, weaned at a later age, and housed differently received TWA training. Results of both studies showed that avoidance of 15-, 17-, and 21-day-old rats is low, but avoidance increases from 21 to 51 days of age. Avoidance of 95- and 200-day-old animals was generally lower than 51-day-old rats. No significant gender differences appeared until 90 days of age; at this age avoidance of males was lower than females. In Experiment III, CS intensity was varied and the US intensity was lower than that used in Experiment I and II. Avoidance of 21- and 90-day-old rats was higher with a more intense CS, but 21-day-olds were still lower than adults. Avoidance of 17-day-old rats was not affected by CS intensity.


Ultrasound by mouse pups from deaf and hearing strains. Pups aged 1 to 10 days, of deaf and hearing mouse strains, were monitored with an ultrasound detector while submitted to standard conditions of cold, isolation, and retrieving. The number of detections varied with the age of the pups and with the type of treatment (as established previously) but not with the genotype of the pups. Thus, occurrence and changes with age in ultrasound emission do not seem to be greatly influenced by their effects upon adult behavior.


Effects of undernutrition in neonatal rats on physical development and food and water regulation. The effects of neonatal undernutrition in rats on food and water regulation, external indices of development, and long-term regulatory behavior were investigated. Undernutrition produced retardation in some external indices of development. The ability to eat, drink, and maintain body weight at weaning were not seriously affected by the undernutrition. Longer term deficiencies in feeding efficiency, osmotic regulation, prandial drinking, and activity were found for experimental subjects. The involvement of peripheral-systemic factors as well as neurological retardation in producing feeding and drinking deficits following undernutrition are discussed.


Effects of amount of contact between mother and child on the mother's nursing behavior. Short-term effects of different amounts of body contact between mother and newborn on human nursing behavior were studied. Extended contact immediately after parturition was related to an increase in affective components of maternal nursing behavior observed on postpartum Days 2 and 4.


Behavioral effects of unilateral basal gangliar lesions in neonatal rats. Two-day-old rats were given unilateral lesions of the caudate-putamen, globus pallidus, or hippocampus and their postural orientation was observed for 30 min immediately after surgery. All groups with damage to the caudate-putamen and/or globus pallidus showed a significant postural deviation toward the side ipsilateral to the lesion. At this age, neurogenesis in the basal ganglia is complete but synapses, neurotransmitters, and enzymes for neurotransmitter synthesis are far below adult levels. These results indicate that the basal ganglia have a role in motor function prior to their full maturation as measured by neuroanatomical and biochemical techniques.


Effects of age and stimulus intensity of the far field auditory brain stem potentials in the laboratory mouse. The vertex-positive, volume-conducted far field response was used to evaluate age-related changes of the 8th cranial nerve and auditory brainstem in the anesthetized C57BL/L mouse. Responses were obtained from stimuli as low as 10 dB (within the 10-20 kHz bandpass). When latencies were compared between 16- and 35-day-old subjects, the older mice had a P1 component which was .175 msec faster, a P2 which was .505 msec faster, a P3 which was .953 msec faster, and a P4 which was 1.315 msec faster. A retest of the younger mice showed that much of this retrocochlear latency decrease occurred between 16 to 18 days postpartum. The latencies of the younger mice were also less likely to decrease as the stimulus intensity was increased from 30 to 70 dB, and this effect was most pronounced at higher neural levels. These age-related changes bear considerable relationship to the development of susceptibility of audiogenic seizures in the mouse.


Circulating alanine production and disposal in healthy subjects. Circulating-alanine production and disposal rates were estimated in eight healthy postabsorptive subjects by means of U-14C alanine and U-14C glucose infusions. The mean circulating-alanine production rate was 368 +/- S.E.M. 28 mumol/min. -1.8(2). Approximately 50 percent of circulating-alanine carbon exchanged rapidly with that of circulating lactate. Approximately 30 per cent of circulating alanine exchanged with protein stores. Other disposal was 29 +/- 2 per cent to circulating glucose and 40 +/- 4 per cent to oxidation. (1) The carbon moieties of circulating alanine and lactate are freely exchangeable. (2) Assessment of the contribution of alanine to gluconeogenesis will depend on establishing the extent to which the precursor pyruvate carbon is derived from glycolysis or from proteolysis. (3) If the principal pyruvate precursor is glycolysis, then the principal specific function of the glucose-alanine cycle appears to be ammonia transport.


24-hour studies of the effects of somatostatin on the levels of plasma growth hormone, glucagon, and glucose in normal subjects and juvenile diabetics. Somatostatin was infused in various doses into normal subjects and juvenile diabetics for a 24-hour period preceded by a 24-hour control period and followed by another three-hour control period. Saline was infused during the first control period. Meals were served during the two 24-hour periods. Blood samples were taken hourly. Five normal males received a total dose of 4 mg. somatostatin. Four male diabetics received 2 mg., four received 4 mg., and four 6 mg. In the diabetics, somatostatin suppressed plasma growth hormone, glucagon, and glucose throughout the infusion. All parameters rebounded at cessation of infusion. In the normals, somatostatin suppressed plasma growth hormone, glucagon, and insulin but increased plasma glucose. It is concluded that the plasma glucose suppression in the diabetics is mainly due to the suppression of the diabetogenic hormones growth hormone and glucagon. A minor effect of decreased and/or delayed absorption of carbohydrates cannot be excluded in these experiments. The elevated plasma glucose levels in normals must be due to the suppressive effects of somatostatin on insulin secretion.


Immunologic insulin resistance.

Immunologic insulin resistance. The efficacy of sulfated beef insulin for plasma glucose control in 35 patients with immunologic insulin resistance was studied. Patients were on a mean dose of 550 U./day (range 200--2,000) of U-500 regular beef insulin. Mean maximum 125I-insulin-binding capacity was 191 mU./ml. serum (range 13--1,080). Mean in vivo half-life (T 1/2) of 125I-regular beef insulin was 614 minutes (range 114--1,300), as against a mean T 1/2 of 13.9 minutes (range 11.8--16.5) in normal controls. Treatment was successful in 34 patients and unsuccessful in one with lipoatrophic diabetes. The mean initial dose of sulfated insulin was 89 U./day (range 15--400) and at three months was 66 U./day (range 20--400). Twenty-eight patients who responded and survived have been on sulfated insulin for a mean of 39 months (range 2-66) and are on a mean dose of 25 U./day (range 0--100). The mean maximum binding capacity fell to 9 mU./ml. (range 0--34) during therapy (p less than 0.01). Mean 125I-insulin T 1/2 fell from 614 to 249 minutes after sulfated insulin therapy (p less than 0.001). A comparative study of 15 patients on consecutive days showed a 35 sulfated insulin T 1/2 of 60 minutes (range 15--94) and a mean 125I-regular insulin T 1/2 of 246 minutes (range 62--560, p less than 0.001). These results indicate that sulfated insulin is less antigenic than regular beef insulin and combines less avidly with human antibodies to regular beef insulin. The response to sulfated insulin therapy was significantly better than the response reported by other investigators to pork insulin or to steroid therapy in similar patients.


Effects of ingestion of triglyceride or galactose on secretion of gastric inhibitory polypeptide and on responses to intravenous glucose in normal and diabetic subjects. Responses of plasma immunoreactive gastric inhibitory polypeptide (IRGIP) to oral triglyceride or galactose were compared in normal and mildly diabetic (non-insulin-dependent) subjects. After triglyceride the responses of IRGIP were similar, but after galactose those of the diabetics were slightly exaggerated. Both stimuli evoked increments of plasma immunoreactive glucagon (IRG) in diabetics but not in normal subjects. Plasma immunoreactive insulin (IRI) did not change. In normal subjects given oral triglyceride or galactose followed by intravenous (I.V.) glucose the early-phase response of plasma IRI was enhanced and glucose tolerance improved. In the diabetics, oral triglyceride did not affect insulin release or glucose tolerance after I.V. glucose; oral galactose elicited a slight increase of insulin release without improving glucose tolerance. In the diabetics the rise of plasma IRG after ingestion of triglyceride or galactose was maintained after I.V. glucose. It is concluded that endogenous GIP is insulinotropic and that there is partial resistance to this action in diabetes. The results were compatible with feedback inhibition of GIP secretion by insulin and with the suggestion that the rise of plasma IRG associated with secretion of GIP in diabetics may be due to the glucagonotropic action of this peptide.


Effect of priming of amino acids on insulin and growth hormone response in the premature infant. Glucose, alpha-amino nitrogen, serum insulin, and HGH were studied in preterm infants during the first 24 hours of life. Glucose infusion (1.25 gm.) resulted in a slight elevation of serum insulin. When this amount of glucose was infused during the last 30 minutes of a two-and-a-half-hour infusion of a mixture of essential amino acids, there was a rapid and striking increase in serum insulin. However, this increase was not associated with a faster glucose disposal rate. The administration of this mixture of amino acids doubled the basal level of alpha-amino nitrogen, and during the first two hours, before glucose infusion, it caused a significant rise of serum insulin and HGH. In both cases glucose caused an increase of HGH secretion that was not significantly different in the two groups of infants.


Insulin-dependent childhood diabetes. Normal viability of cultured fibroblasts. Cultured skin fibroblasts from clinically normal offspring of two parents with non-insulin-dependent diabetes have demonstrated premature senescence as a decreased ability of cells to establish colonies when inoculated at low density (plating efficiency). The present study tested the hypothesis that there is an inherent cellular defect affecting viability of diabetic cells in insulin-dependent diabetes. Four insulin-dependent patients, aged 12 to 19 years, included two with joint contracture, skin changes, and growth failure; one with thyroiditis and past history of nephrosis; and one with a family history of insulin dependency. Ten control subjects, aged 10 to 52 years, had negative family histories and normal oral glucose tolerance tests. Number of cells per confluent dish correlated significantly with donor age (p less than 0.001) at 30 and 40 in-vitro generations. The patients' cells' mean confluent density did not differ from that of five age-matched controls. Plating efficiency correlated with donor age at 30 in-vitro generations ( p less than 0.001); plating efficiency of cells from the youngsters with diabetes was virtually identical to that of control cells at 20, 30, and 40 generations. In this small series of two subjects with in-vivo growth failure, one with associated autoimmune disease and another with familial insulin-dependent disease, cultured fibroblasts demonstrated normal viability and the hypothesis of a cellular growth defect was not confirmed.


A simplified assay of hemoglobin AIc in diabetic patients by use of isoelectric focusing and quantitative microdensitometry. Isoelectric focusing (IEF) of human erythrocyte hemolystaes on polyacrylamide slab gels over a pH gradient of 6 to 8 provides sufficient resolution of hemoglobin AIc (HbAIc) from other hemoglobin components (AIa, AIb, AII, S, and F) to allow quantification by high-resolution microdensitometry. Twice-chromatographed HbAIc alone and in admixtures with normal and diabetic hemolysates were employed to verify the identification and quantification of the AIc component. Relative concentration was determined as a per cent of the total hemoglobin absorption at 556 nm on acid-fixed, unstained gels. A total of 60 patient samples were examined by IEF, and, for 35 samples, both column chromatography and IEF determination were obtained, revealing excellent correlation between these two methods.


Effect of glucose on the glucagon response to L-dopa in normal and diabetic subjects. The effect of an oral dose of 1 gm. L-dopa either without or after a concomitant oral administration of 100 gm. glucose on the plasma level of pancreatic glucagon, plasma immunoreactive insulin (IRI), and plasma growth hormone (GH) was assessed in eight normal and 10 insulin-treated diabetic subjects. In the normal group the stimulatory effect o L-dopa on pancreatic glucagon release was reconfirmed. Moreover, in the diabetics essentially the same plasma glucagon increase after drug administration was found, such a response being inhibited in both groups by glucose. The increase of plasma GH after L-dopa in both healthy persons and diabetics and the inhibition of this response by glucose in healthy subjects was reconfirmed. Furthermore, the same effect of exogenous glucose on the L-dopa induced GH release was observed in diabetics. It may be concluded that glucagon may play a pathogenetic role in the worsening of parkinsonian diabetic patients during the treatment with L-dopa and that diabetic hyperglycemia per se seems to be insufficient for an inhibition of the release of both glucagon and GH AFTer L-dopa.


Circulating alanine disposal in diabetes mellitus. Alanine was selected for study as a representative circulating glucose precursor in relation to the question of the source of the excess circulating glucose in diabetes mellitus. U-14C alanine and U-14C glucose infusions were given to healthy subjects and to subjects with untreated mild maturity, severe maturity, and juvenile diabetes. Comparative studies after a 24-hour fast were made in healthy and in mildly diabetic subjects. The alanine production rate was unaltered by fasting or diabetes. The glucose production rate was unaltered by fasting but increased in diabetes in relation to the severity of the disease. The fractions of alanine-to-glucose and of glucose-from-alanine were increased by fasting. The effect of diabetes was different. The fraction of alanine-to-glucose was much less in mild maturity diabetes than in health, and it was increased only in juvenile diabetes. In all the diabetic groups the glucose-from-alanine fraction was much less than in health. In every group the change in the alanine oxidation rate was reciprocal to that in the alanine-derived glucogenesis rate. The results are consistent with the possibility that the principal source of the excess circulating glucose in diabetes is glycogen.


Computerized tomography in the study of West's syndrome. 37 children presenting with West's syndrome were studied by computerized tomography scanning. An abnormality consisting of diffuse cerebral atrophy, predominating in the fronto-temporal region, was demonstrated in 30 cases. The abnormality was sometimes associated with calcification (tuberous sclerosis) or malformation (agenesis of the corpus callosum). The aetiology of the atrophy and its relationship to clinical and electroencephalographic signs is discussed. Computerized tomography scanning is recommended for children with West's syndrome in order to distinguish between primary and secondary cases, and for greater prognostic accuracy.


Agenesis of the corpus callosum: report of two pre-school children and review of the literature. The results of neuropsychological examinations of two patients with agenesis of the corpus callosum showed low intelligence-test performance, impared visuo-motor co-ordination and impaired bimanual co-ordination. The most striking deficits were observed in Case A, particularly in her inability to identify objects verbally when placed in the non-dominant hand, and in her ability to complete a task with the non-dominant hand without vision, when she was unable to complete the same task with vision. This patient is unusual insofar as she manifests deficits noted in acallosal patients, as well as some noted in split-brain patients but not previously ascribed to acallosal patients.


Psychomotor development of infants and children after profound hypothermia during surgery for congenital heart disease. We assessed neurological status and cognitive, verbal, social and motor skills of 17 children who had undergone cardiac surgery under profound hypothermia, and of seven siblings (controls). None of the subjects had significant neurological impairment. The mean development quotient (DQ) for the patients was 92.5 (in the low-average range) and for the controls was 103 (average). The DQ of one patient (71) was below the normal range. Development of the patients was comparable with that reported by other authors for children with cyanotic congenital heart-disease who have not undergone cardiac surgery. It correlated with the type of congenital heart-disease but not with the duration of hypoxic arrest. It is concluded that profound hypothermia can be used safely during the correction of cardiac defects in infants, without fear of retarding psychomotor development.


Inter- versus intra-hemispheric learning in dyslexic and normal readers. The present study investigated the hypothesis that developmental dyslexia is attributable to dysfunction in inter-hemispheric transfer. Dyslexic and normal readers in second grade (age-range seven to eight years) and sixth grade (11 to 12 years) were given tachistoscopic presentations of novel visual stimuli (Chinese ideographs), randomly presented to the left and right visual fields and to the central fixation point. Each stimulus was paired with a common English word (spoken) and the children were asked to associate the two. The transmission deficit hypothesis predicts that poor and normal readers will be differentiated in the case of presentations to the right hemisphere (left visual field) but will not differ significantly in the case of presentations to the left hemisphere (right visual field). This hypothesis was not supported. Normal readers at both grade levels performed significantly better than poor readers in both visual-field presentations.


Reliability of goniometric measurements of hip motion in spastic cerebral palsy. Reliability of goniometric measurements of ranges of motion in the right hip of four children with mild or moderate spastic diplegia was studied by comparing results when physical therapists used specific and non-specific measurement instructions. Measurements of hip extension, abduction and external rotation were made. The use of specific measurement instructions improved inter-rater reliability only in the case of external rotation. Inter-session reliability was not improved by the use of specific measurement instructions. It is concluded that goniometric measurements have such a low level of reliability that they can only be used to assist clinical judgment, and that they are not sufficiently reliable to be used in studied of cerebral palsy.


Gastro-esophageal reflux in severely retarded children. Eight severely mentally retarded children with histories of recurrent vomiting, anemia and chest disease are reported. It is suggested that appropriate medical management improves the quality of life for such children and may also reduce the number of hospital admissions for the treatment of this cluster of symptoms. Symptoms of vomiting, anemia and recurrent pneumonia in retarded children should suggest gastro-esophageal reflux. Investigations should include the upper gastrointestinal tract, with specific attention being paid to esophageal reflux.


Histological patterns of muscle in infants with developmental brain abnormalities. The histology of muscle obtained from 23 hypotonic infants without neuromuscular disease is presented. Long-term follow-up neurological examinations were carried out to determine the site of the lesion. 18 cases have strong evidence of cerebral dysfunction, 12 of whom have histologial abnormalities of fiber-type distribution and diameter. Of the remaining five patients without obvious cerebral abnormality, four also had histological changes, but individual circumstances partially explain the cause of the abnormal histological patterns in these four. No single histological abnormality could be identified, but the results indicate that histological abnormalities of muscle in hypotonic infants without clinical or microscopic evidence of neuromuscular disease may be useful in predicting a cerebral cause for the hypotonia.


A polygraphic study of bioelectrical brain maturation in preterm infants. Bioelectrical brain maturation was studied in 26 low-risk preterm infants by serial polygraphic recordings. A modified method of visual EEG analysis was used, based on Parmelee's coding system, which allowed quantification. It gave the following results: (1) The main characteristics of EEG maturation in preterm infants were a progressive spatio-temporal differentiation, with an increase of rhythmic activities and a decrease of discontinuity. (2) A strong relationship was found between post-menstrual age of the infants and EEG maturity, but there were exceptions to this rule. (3) longer duration of extra-uterine life had a small accelerating influence on EEG maturation. (4) Certain basic types of EEG patterns were closely related to behavioural states, whereas EEG maturity was not state-dependent. (5) The relationship between EEG pattern types and behavioural states becomes more stable with increasing age.


A study of six cases of de Lange Amsterdam dwarf syndrome, with special attention to voice, speech and language characteristics. From a survey of southern Scotland, six severly handicapped subjects (age-range 8 to 22 years) were established by firm criteria as suffering from the de Lange Amsterdam Dwarf syndrome. They showed a high incidence of behaviour disturbance. Language development was retarded and all but one of the subjects were dysphonic. A connection may exist between the glottal "fry" (an unperiodical phonation of the vocal folds in a frequency below the normal pitch register) observed in the cries of the younger non-speaking cases and the hoarseness in the speech of the older subjects.


A modular seating system for cerebral-palsied children. A seating system for physically handicapped children has been devised in which a series of standard components (neck supports, rolled seats, pommels) can be incorporated to make a seating system appropriate for the individual child.