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5b7ef4b1-dd34-4ae7-9ece-45b52fac0c46
| 1 |
In connection with the fact that the Conference was devoted to the early diagnosis and therapy of C.P., problems concerning the lower age groups of children were debated. The Conference discussed the definitions of "cerebral palsy" used in the literature, the clinical forms, the auxiliary diagnostic methods and their significance in the diagnosing of this pathological syndrome.
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5b7ef4b1-dd34-4ae7-9ece-45b52fac0c46
| 2 |
Early clinical symptoms, enabling to establish the diagnosis of cerebral palsy were particularly extensively debated. In the latter problem particular attention was paid to the diagnostic value of kinetic automatisms of the group of tonic posture reflexes and dysfunctions of the kinetic pattern in children. It was underlined in the debate the C.
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5b7ef4b1-dd34-4ae7-9ece-45b52fac0c46
| 3 |
P. was no separate clinical disease, but a pathological syndrome arisen as a result of the negative influence of different factors and yielding very diverse clinical and neurolopathologic symptoms, according to the kind of noxious factors and the period and degree of maturity of the nervous system in which they acted.
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5b7ef4b1-dd34-4ae7-9ece-45b52fac0c46
| 4 |
The participants in the debate also sressed that, as the child develops and is observed for a longer period it is fairly often necessary to check this diagnosis, as C.P. may prove, as the time passes, to be a degenerative syndrome, a pressure syndrome etc. The psychologists participating in the Conference discussed the psychological problems of the child with C.
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5b7ef4b1-dd34-4ae7-9ece-45b52fac0c46
| 5 |
P. and also the early diagnosis of the pathological syndrome debated. The diversity of the symptoms of the C.N.S. in children suffering from C.P. was underscored, as--apart from dysfunctions within the kinetic area, there can be present sight, hearing and speech dysfunctions, those of sensory perceptions and mental development.
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5b7ef4b1-dd34-4ae7-9ece-45b52fac0c46
| 6 |
These children require multispecialist care, as everyone of dysfunctions mentioned may present a complicated diagnostic problem. Plenty of place was devoted to the discussion of problems connected with epilepsy in children with C.P. Also extensively debated were the general principles of the medical procedure in children with C.
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5b7ef4b1-dd34-4ae7-9ece-45b52fac0c46
| 7 |
P. As a result of the discussion it was decided that children with severer forms of C.P. and those from poor social conditions should be subjected to long-lasting sanatorium rehabilitation. Keeping the child in its family environment should, however, be the generally adopted principle of the rehabilitation of a little child.
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5b7ef4b1-dd34-4ae7-9ece-45b52fac0c46
| 8 |
The parents of the child should be trained in the proper rearing of the child under household conditions, a manner to secure all the needs resulting from the then stage of its development. In connection with this problem the project of the programme of sensoric-and-kinetic rehabilitation was debated, as presented by psychologists and rehabilitants (kinesitherapeuts).
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3b84508e-276c-4bb0-9294-22613673a51b
| 0 |
[Congenital heart malformations in neonates, infants and young children (author's transl)]. Congenital heart malformations in neonates, infants and young children represent the main problem of paediatric cardiology in Poland. Congenital cardiovascular diseases (incidence also approximately 8 per 1000 in liveborn infants) cause very high mortality, particularly in the neonatal and infantile period. Approximately 5000 live-born children are affected every year by serious heart malformations.
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3b84508e-276c-4bb0-9294-22613673a51b
| 1 |
For at least two thirds of these previously hopelessly ill infants there are real possibilities of effective medical and surgical treatment. Not only a considerable drop in mortality in the earliest infancy would be achieved, but: a further normal physical and psychical growth and development of these children would be possible.
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3b84508e-276c-4bb0-9294-22613673a51b
| 2 |
At present, however, the available possibilities are by far not sufficient, as in all hitherto functioning centres we were able to manage 200-300 children yearly, whereas the real needs are at leasttenfold greater. Therefore it is necessary to: Increase the number and capacity of hospital wards capable enough to provide the intensive cardiopulmonary care;
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3b84508e-276c-4bb0-9294-22613673a51b
| 3 |
to execute appropriate reorganization aimed to concentrating the appropriate specialists (pediatric cardiologists, radiologists, surgeons, anesthesiologists, nurses) and equipment (cardiological and cardiosurgical appliances, X-ray equipment, intensive care units etc.) in centres designated for the above tasks. At least 7 paediatric intensive care and cardiosurgical centres should be instituted in Poland for a satisfactory management of congenital heart diseases.
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f9122667-c94d-4584-b821-9334e84a6362
| 0 |
[Ribonuclease activity in the serum of children of various ages (author's transl)]. The normal levels of ribonuclease activity in the serum of children of both sexes of various ages. The children into four age groups: thee 1st grous--from 1 to 7 days of age, the 2nd--from 1 to 12 months, 3rd--from 1 to 3 years, 4th--from 7 to 14 years of age.
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f9122667-c94d-4584-b821-9334e84a6362
| 1 |
The ribonuclease activity amounted, in the various age groups, respectively tto: 1st group--0.27+0.07 ug/ml of serum, 2nd--0.21+0.06 ug/ml, 3rd--0.15+0.04 ug/ml, 4th--0.14+0.04 ug/ml.
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50ada18a-e227-4d1b-b388-f0fb6442d9c1
| 0 |
Activation and nuclear translocation of protein kinase during transsynaptic induction of tyrosine 3-monooxygenase. The tyrosine-3-monooxygenase activity [L-tyrosine, tetrahydropteridine: oxygen oxidoreductase (3-hydroxylating); EC 1.14.16.2] of rat adrenal medulla is induced 20-24 hr after the injection of reserpine (16 mumol/kg intraperitoneally).
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50ada18a-e227-4d1b-b388-f0fb6442d9c1
| 1 |
This and other inducing stimuli increase the 3': 5'-cyclic AMP (cAMP) content in the medulla for longer than 60 min and activate the cAMP-dependent protein kinase (ATP: protein phosphotransferase; EC 2.7.1.37) for several hours. Corticotropin (ACTH), dopamine, and propranolol do not induce the monooxygenase, but elicit an increase in the cAMP content of the medulla which fails to activate protein kinase and lasts less than 1 hr.
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50ada18a-e227-4d1b-b388-f0fb6442d9c1
| 2 |
A high- and low-molecular-weight protein kinase are separated by gel filtration from the 20,000 X g pellet extract of adrenal medulla homogenate. The activity of the low-molecular-weight enzyme is expressed as its ability to phosphorylate histone. The protein kinase activity of the pellet is increased between 3 and 17 hr after reserpine injection.
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50ada18a-e227-4d1b-b388-f0fb6442d9c1
| 3 |
Our evidence indicates that this increase is due to a translocation from cytosol to subcellular structures of a kinase that utilizes lysine-rich histone as phosphate acceptor. The protein kinase activity that is extracted from a purified nuclear fraction prepared from the adrenal medulla of rats injected 7 hr previously with reserpine is greater than that extracted from medulla of saline-treated rats.
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041d447d-e072-4ca1-8e0a-8895ea3efd19
| 0 |
A 15-hydroxyprostaglandin dehydrogenase specific for prostaglandin A in rabbit kidney. Examination of a soluble fraction derived from homogenates of rabbit kidney papilla revealed the existence of a 15-hydroxyprostaglandin dehydrogenase specific for A-type prostaglandins. Prostaglandins of the E- and F-series were not substrates for this enzyme.
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041d447d-e072-4ca1-8e0a-8895ea3efd19
| 1 |
In agreement with published data, the 15-hydroxyprostaglandin dehydrogenase(s) derived from the kidney cortex were found to degrade all prostaglandins examined (PGE, PGF, PGA) in the presence of added cofactor NAD. Thus it is evident that in this species the kidney 15-hydroxyprostaglandin dehydrogenases are anatomically compartmentalized so that the papilla is able to metabpable of degrading E-, F-, and A-type prostaglandins by this metabolic pathway.
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c4730993-68c2-48e5-92ef-d26652c899e6
| 0 |
Specific positions involved in enzyme catalyzed covalent binding of benzo[a]pyrene to poly(G). Covalent binding of benzo[a]pyrene to poly(G) was studied with the use of a radioactive assay and specifically labeled substrates to define the role of the 1, 3- and 6-positions of the hydrocarbon during this process.
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c4730993-68c2-48e5-92ef-d26652c899e6
| 1 |
Binding was shown to be dependent on microsomes, NADPH, O2 and poly(G). 7, 8-Benzoflavone and 2', 2'-diethylaminoethyl-2, 2-diphenyl valerate were inhibitory w.hereas modulators of epoxide hydrase activity had little effect. 3H and 14C studies suggested a possible loss of one to two protons.
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c4730993-68c2-48e5-92ef-d26652c899e6
| 2 |
Incorporation of [6-3H1]benzo[a]pyrene provided evidence that the 6-position of the hydrocarbon was not metabolized during covalent attachment to poly(G) and, furthermore, results with [1, 3, 6-3H]benzo[a]pyrene suggest that the 1- and 3-positions may not be involved either.
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c4730993-68c2-48e5-92ef-d26652c899e6
| 3 |
After scaling up of the standard assay 20-fold, characterization of the tritiated BaP-poly(G) complex was carried out by hydrolysis and subsequent chromatography. Thin-layer chromatography of the isolated hydrolysis products treated with HCl or alkaline phosphatase indicated that the complex formed between BaP and poly(G) was covalently linked and composed of hydrocarbon-nucleotide(s).
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18225ee4-c30a-4f83-99a3-d8eb366ce912
| 0 |
Simple model for hormone-activated adenylate cyclase systems. A simple model is developed to explain the activation of rat liver plasma membrane adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] by guanosine nucleotides and glucagon and the dependence of the cATALYTIC RATE ON Mg2+, H+, and substrate concentrations.
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18225ee4-c30a-4f83-99a3-d8eb366ce912
| 1 |
The basic model proposes that the adenylate cyclase system can exist in two states, A and B; that activating ligands bind preferentially to the B state; and that only the B state is active. Kinetic data are quantitatively fit to this model, and the binding constants for the interaction of the A and B states with glucagon, GTP, and guanyl-5'-ylimidodiphosphate are obtinaed.
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18225ee4-c30a-4f83-99a3-d8eb366ce912
| 2 |
The substrates ATP and adenyl-5'-ylimidodiphosphate appear to show little preference between the A and B states, and simple Michaelis-Menten kinetics are sufficient to describe the dependence of the catalytic rate on substrate concentration under optimal conditions. The dependence of the rate on pH can be explained by postulating that one ionizable group in its acid form and one ionizable group in its basic form must be present at the active site in order for catalysis to occur.
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18225ee4-c30a-4f83-99a3-d8eb366ce912
| 3 |
The activation and inhibition of the activity by Mg2+ can be explained by a similar mechanism with Mg2+ binding to activating and inhibiting sites. Glucagon and guanosine nucleotides appear to influence the dependence of the rate on Mg2+ and glucagon. The Mg2+ also may display some preference for the B state.
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18225ee4-c30a-4f83-99a3-d8eb366ce912
| 4 |
A comparison of this model with others that have been proposed is given. The proposed model appears to provide a simple conceptual frame-work that is applicable to many adenylate cyclase systems.
|
980b6fc7-610e-40e6-88e2-5ee27099bffc
| 0 |
Heat mutagenesis in bacteriophage T4: the transition pathway. G-C leads to A-T transitions are induced by heat, and arise from the deamination of cytosine (5-hydroxymethylcytosine in the case of bacteriophage T4) generating uracil. The reaction is proton-catalyzed, and is also characteristic of acid mutagenesis.
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980b6fc7-610e-40e6-88e2-5ee27099bffc
| 1 |
Mutation rates and activation energies of mutation are site-specific, and are presumably influenced by neighboring bases. Rates of heat-induced mutation in bacteriophage T4 under conditions of temperature, pH, and ionic strength similar to those prevailing in higher eukaryotic cells suggest that heat mutagenesis may present a serious challenge to organisms with large genomes, and may comprise an important determinant of the rates of spontaneous mutation.
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d9c1825d-bbc0-4714-ab43-13000451df08
| 0 |
beta-adrenergic receptors in rat liver: effects of adrenalectomy. The response of rat liver adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] to catecholamines is enhanced after adrenalectomy. To investigate this phenomenon, we developed an in vitro assay for beta-adrenergic receptors of plasma membranes derived from livers of control and adrenalectomized rats, using [125I]iodohydroxybenzylpindolol (IHYP), a potent beta-adrenergic receptor antagonist.
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d9c1825d-bbc0-4714-ab43-13000451df08
| 1 |
Binding of IHYP reached equilibrium within 30 min and dissociation occurred with a half-time of approximately 60 min. The l-isomers of isoproterenol and propranolol were at least 50 times more potent as inhibitors of IHYP binding than were the corresponding d-isomers. Adrenalectomy did not affect the rates of association or dissociation of IHYP or the dissociation constants of several ligands that are active at beta-adrenergic receptors.
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d9c1825d-bbc0-4714-ab43-13000451df08
| 2 |
The number of binding sites for IHYP was determined in homogenates and in purified membranes of livers from control and adrenalectomized rats. The number of sites increased 3- to 5-fold after adrenalectomy. A similar increase in hormone stimulation of adenylate cyclase was observed. These changes were reversed by the administration of cortisone.
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d9c1825d-bbc0-4714-ab43-13000451df08
| 3 |
The increase in the number of binding sites for IHYP may be a compensatory response to the impairments in gluconeogenesis and glycogenolysis which occur after adrenalectomy.
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c1ac9ddb-446d-49d6-90c2-b7052bfbdfc3
| 0 |
Thermodynamic studies of polymerization of deoxygenated sickle cell hemoglobin. Solubilities of deoxygenated sickle cell hemoglobin (deoxy-Hb S), at varying pH and temperature over a range of concentrations encompassing those found in erythrocytes, were measured. The technique involved ultracentrifugation, which gave values of the supernatant concentration and the mass of the sedimented material.
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c1ac9ddb-446d-49d6-90c2-b7052bfbdfc3
| 1 |
The data establish that the solubility of doexy-Hb S is the saturation concentration and is independent of initial concentration. The mass of the pellet phase increases linearly with initial concentration. Moreover, the saturation concentration represents the critical concentration above which monomers are in equilibrium with polymers. These polymers are the putative cause of erythrocytes deformation associated with sickle cell anemia.
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c1ac9ddb-446d-49d6-90c2-b7052bfbdfc3
| 2 |
The solubility-pH profiles of deoxy-Hb S at various temperatures, unlike those of other proteins, show no minima at the isoelectric pH but instead show a marked decrease in solubility below pH 7.0, indicating the predominance of polymerization over the expected increase in solubility. Deoxy-Hb S, within specified ranges of temperature and pH, possesses a negative temperature coefficient of solubility, a property characteristic of hydrophobic interactions.
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c1ac9ddb-446d-49d6-90c2-b7052bfbdfc3
| 3 |
The saturation concentration is, however, temperature independent at conditions close to physiological. The enthalpy of polymerization (3.5 kcal/mol) is temperature independent from 6 degrees to 22 degrees for all pH values between 6.45 and 7.40. In the range of 22 degrees to 38 degrees, this parameter becomes less endothermic, having a value of 2.5
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c1ac9ddb-446d-49d6-90c2-b7052bfbdfc3
| 4 |
kcal/mol at pH 6.45 and a value of zero at pH 7.20. Such behavior of the system suggests a phase transition near 22 degreas. Within the range of conditions examined the polymerization is entropically driven.
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e859df74-cfd8-486a-a5bd-fe571ad8fe31
| 0 |
Difference in the number of insulin binding sites between cortisol-sensitive and cortisol-resistant lymphoma P1798 cells. Cortisol-sensitive and cortisol-resistant lymphoma P1798 cells specifically bind [25I]insulin. Resistant lymphocytes bind 40% less insulin than sensitive cells. These results suggest that insulin (or insulin-like substances) may play a role in growth regulation and/or response of this tumor to glucocorticoid therapy.
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8363b78a-c1d4-4d6c-95cc-6e06374c6e3a
| 0 |
Action of histamine and its receptor blockers on uterine circulation in sheep. Effects of iv and ia administration of histamine and its H1 and H2 blockers (diphenhydramine and metiamide) on systemic arterial pressure, heart rate, and uterine and iliac blood flows were investigated in unanesthetized, chronically instrumented nonpregnant ewes.
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8363b78a-c1d4-4d6c-95cc-6e06374c6e3a
| 1 |
Intravenous histamine produced tachycardia, hypotension, and decreased iliac and uterine blood flows. In contrast, ia injections produced a significant increase in blood flows in these vascular beds which was dose-dependent. Evidence is presented to show that some of the circulatory actions of histamine may be related to stimulation of H1 while others may be related to H2 receptors.
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8363b78a-c1d4-4d6c-95cc-6e06374c6e3a
| 2 |
The peripheral circulatory action produced by iv histamine is probably secondary to its effects on reducing cardiac output. The uterine and iliac vascular beds contain mostly H1 receptors since their response to histamine can be blocked almost totally by Benadryl and not by H2 antagonist metiamide.
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7d6c3cc1-02df-4de5-b62e-9d6b08c40617
| 0 |
Alpha-MSH and MIF-2 effects on serotonin levels and accumulation in various rat brain areas. Levels as well as accumulation of serotonin (5-HT) were measured in various brain regions of the rat after administration of alpha-melanocyte-stimulating hormone (MSH) and Pro-Leu-Gly-NH2 (MIF-I).
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7d6c3cc1-02df-4de5-b62e-9d6b08c40617
| 1 |
The method used in determining the serotonin measured both 5-OH-tryptamine (5-HT) and 5-methoxytryptamine (5-MT). No statistically significant changes in levels or accumulation of serotonin after pargyline injection were found when unoperated control rats were treated with either MSH or MIF-I. Similar treatment of hypophysectomized rats indicated that both peptides significantly (p less than 0.05
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7d6c3cc1-02df-4de5-b62e-9d6b08c40617
| 2 |
) lowered serotonin accumulation only in the area of the frontal cortex; a similar but smaller, not statistically significant, decrease was seen in the hypothalamus and hippocampus of the hypophysectomized rat. Since only hypophysectomized rats were affected, no correlation between the behavioral effects of these peptides (which has been found to occur in both unoperated and hypophysectomized rats) and the biochemical changes could be made.
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95928dd5-0c7e-41ae-8684-c64814de9a15
| 0 |
Alpha-MSH and MIF-I effects on catecholamine levels and synthesis in various rat brain areas. Attempts were made to find a biochemical correlate with previously observed behavioral alterations after administration of alpha-melanocyte-stimulating hormone (MSH) and MSH release-inhibiting factor (MIF-I). Brains of intact and hypophysectomized (hypox) rats were analyzed for endogenous catecholamine levels and the disappearance rate of endogenous norepinephrine (NE) after treatment with the tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine (AMPT).
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95928dd5-0c7e-41ae-8684-c64814de9a15
| 1 |
The studies undertaken show the following: (1) After the injection of MSH (100 mug/kg IP daily x 3) and AMPT, samples in different groups of intact and hypox rats were taken at 0, 1, 2, 4 and 6 hrs in 7 different brain areas.
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95928dd5-0c7e-41ae-8684-c64814de9a15
| 2 |
In the mid-brain area for the intact group of rats, the rate of disappearance of NE was faster and for the hypox rats it was slower than the rate for control rats not treated with the peptides. NE levels in the same area at time 0 were 11 percent lower than controls in hypox rats and unchanged in unoperated animals.
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95928dd5-0c7e-41ae-8684-c64814de9a15
| 3 |
(2) After the injection of MIF-I (20 mg/kg IP daily x 3) in similar experiments as with MSH, a reduced rate (p less than 0.05) of NE disappearance for the first 4 hr and an increased rate (p less than 0.05) of NE disappearance for the last 2 hr of the experiments occurred for both the intact and hypox rats in the mid-brain area where endogenous NE levels were lowered by 11 and 12 percent at 0 min.
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95928dd5-0c7e-41ae-8684-c64814de9a15
| 4 |
In no other brain areas were alterations in NE breakdown found in both the intact and hypox rat groups. Behavioral changes have been found previously under similar experimental conditions in both intact and hypox rats. (3) Rates of dopamine disappearance in experiments similar to those described for NE disappearance indicated that in the striatal brain area no change was found in the intact rats after either MSH or MIF-I, whereas a decrease in DA disappearance was found for hypox rats during the six hour experimental period only after MSH.
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95928dd5-0c7e-41ae-8684-c64814de9a15
| 5 |
The results indicate that a correlation between behavioral changes, rates of disappearance and endogenous levels of NE in the mid-brain area may occur after MIF-I at the times examined but that a similar correlation for MSH did not appear likely.
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07f9cae3-b09a-4d47-899e-22f810b50127
| 0 |
Self-administration of psychomotor stimulant drugs: the effects of unlimited access. Rhesus monkeys surgically prepared with intravenous catheters were given 23 hr daily access to injection of either cocaine, d-amphetamine, 1-amphetamine, d-methamphetamine or diethylpropion on a fixed ratio 1 schedule of reinforcement for a maximum of 30 days.
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07f9cae3-b09a-4d47-899e-22f810b50127
| 1 |
Responding was maintained by all these drugs but showed both day-to-day and hour-to-hour variability. The two animals self-administering 0.2 mg/kg/infusion cocaine died in less than 5 days. All 6 animals given access to 0.05 mg/kg/infusion d-amphetamine or 0.025 mg/kg/infusion d-methamphetamine also died, but tended to survive more days than animals exposed to cocaine.
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07f9cae3-b09a-4d47-899e-22f810b50127
| 2 |
Three of the 5 animals whose responding was maintained by 0.5 mg/kg/infusion diethylpropion and one of the two animals whose responding was maintained by 0.05 mg/kg/infusion 1-amphetamine survived the entire 30 days despite high rates of intake. Food intake was initially decreased, but often returned to predrug levels and was not related to level of drug intake.
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0b4de25a-310b-4e1a-aad5-960f982dd0a5
| 0 |
Rate-dependent effects of drugs: a review of the literature. It has been claimed that the effects of amphetamines on schedule-controlled behavior depend to a large extent on the rate of responding in control conditions. A review of the literature shows that there is considerable support for this hypothesis if the behavior is not suppressed by aversive procedures, is not under the control of powerful external stimuli or is not occurring very infrequently.
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0b4de25a-310b-4e1a-aad5-960f982dd0a5
| 1 |
The extension of a rate-dependency hypothesis to the effects of other drugs has less empirical support, however. It is argued that many of the procedures used for studying rate-dependent drug effects do not provide critical tests of the hypothesis. If it is to be shown unequivocally that it is rate of operant responding which determines the behavioral effects of drugs, procedures are needed in which other varibles such as reinforcement frequency are more adequately controlled.
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c0114d28-1670-4b80-9051-32c25345fa0c
| 0 |
Effect of various 6-hydroxydopamine treatments during development on growth and ingestive behavior. Destruction of catecholamine-containing fibers in brain at 5 days of age with intracisternal injection of 6-hydroxydopamine reduced body growth, intake of a sucrose solution, and acquisition of an active avoidance response. Further characterization of behavioral deficits indicated that treated animals also showed reduced ingestion of saline solution when injected with desoxycorticosterone and a decreased eating response to insulin.
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c0114d28-1670-4b80-9051-32c25345fa0c
| 1 |
In addition, all of these deficits produced by catecholamine depletion with 6-hydroxydopamine were observed in rats in which brain dopamine was preferentially reduced but not in rats having preferential destruction of noradrenergic fibers, suggesting that dopamine depletion amounts for the observed alterations in developing animals. Although animals treated with 6-hydroxydopamine at 14 days showed reduced intake of a sucrose solution, they did not have reduced growth.
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c0114d28-1670-4b80-9051-32c25345fa0c
| 2 |
Since early malnourishment reduced growth, it seems possible that the reduced growth observed after destruction of dopaminergeic fibers may be related to an acute reduction of food intake which is perpetuated by persistent deficits in ingestive behavior. Evidence implicating malnourishment in other deficits produced by 6-hydroxydopamine could not be obtained.
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8a0b98c8-666d-40c6-ba88-6c99efdbd659
| 0 |
Schedule-induced oral self administration of etonitazene. Rats were induced to drink either a saline-etonitazene solution or a saline solution with a schedule-induced polydipsia paradigm. When water was freely available, the rats continued to drink the saline solution or the saline-etonitazene solution, rather than the water.
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8a0b98c8-666d-40c6-ba88-6c99efdbd659
| 1 |
When the locations of the solutions were switched, the rats that were drinking saline switched to water (drank at the usual location), but the rats that were drinking saline-etonitazene continued to drink the saline-etonitazene solution (drank from the bottle at the other location). Naloxone administration temporarily eliminated the drinking of saline-etonitazene solution, but not that of saline solution.
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c8433960-2b01-471c-9fb8-cec66c80be4d
| 0 |
Enzyme activity in sleep and sleep deprivation. Liver tyrosine transaminase activity is low during the day when the rats are mostly asleep and high during the night when they are awake. When wakefulness was imposed for 8 hr during daylight on the day of the experiment and the rats were allowed to sleep for the following 3 hr during darkness, the tyrosine transaminase activity became high during the day and low at night.
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c8433960-2b01-471c-9fb8-cec66c80be4d
| 1 |
That this reversal in enzyme activity is not mediated by the pituitary-adrenal axis is demonstrated by the fact that in adrenalectomized rats tyrosine transaminase activity increased during the day in the sleep deprived rats. However, in these rats the enzyme activity did not become low in the sleep-deprived-sleeping condition.
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c8433960-2b01-471c-9fb8-cec66c80be4d
| 2 |
Changes in tryptophan pyrrolase activity during sleep deprivation were demonstrated to be mediated by the pituitary-adrenal axis.
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58bac4c6-fdec-42ca-b678-cf348ccfbd00
| 0 |
The genetics of the mimetic butterfly Hypolimnas bolina (L.). Hypolimnas bolina is a Nymphalid butterfly having a west to east distribution from Madagascar to Easter Island, and a north to south one from Japan to Australasia. It is highly migratory in some areas. In much of the western part of its range the female is both monomorphic and a mimic of Euploea.
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58bac4c6-fdec-42ca-b678-cf348ccfbd00
| 1 |
Further east it is frequently polymorphic with the majority of the forms being non-mimetic. The polymorphism is sex-limited to the female and controlled by two unlinked loci, one with two allelomorphs, E and e, determining the extent of the dark pigmentation, the other with three allelomorphs, P, Pn and p, determining the presence and distribution of orange-brown.
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58bac4c6-fdec-42ca-b678-cf348ccfbd00
| 2 |
Only butterflies of the genotypes EEpp and to a lesser extent Eepp are satisfactory Batesian mimics of their Euploea models. The details of the mimetic pattern are under multifactorial control, following those of their local model, as is much of the variation within the non-mimetic forms, particularly with regard to the distribution of white and blue scaling.
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c570330e-552d-4ba9-b799-685c0179f270
| 0 |
Terrestrial vertebrates of the New Hebrides: origin and distribution. The known terrestrial vertebrate fauna of the New Hebrides consists of 16 species of mammals (excluding feral domestic stock), 61 species of resident land- and freshwater birds, 20 species of reptiles and one amphibian. Of these, three, five, four and one species respectively have apparently been introduced by man.
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c570330e-552d-4ba9-b799-685c0179f270
| 1 |
The non-introduced fauna is clearly Indo-Australian in origin, but some species have an exclusively Pacific island distribution and others (two bats, seven birds, and four lizards) are endemic. On the six islands visited 95 out of the possible 98 vertebrate species occur. Santo, the largest and most northerly island, supports the richest fauna.
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c570330e-552d-4ba9-b799-685c0179f270
| 2 |
The comparative impoverishment of more southerly islands is not directly attributable to the progressive increase in isolation and distance from presumptive source area, nor to decrease in island area or maximum height.
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b8d246b5-e6ee-4dbc-9479-9195f300455c
| 0 |
5-Aminolaevulinic acid dehydratase: structure, function, and mechanism. delta-Aminolaevulinic acid dehydratase catalyses the synthesis of porphobilinogen. The enzyme has a molecular mass of 285000 and is composed of eight similar subunits of molecular mass 35000. The N-terminal amino acid is acylated, and the number of peptides found on tryptic digestion equals the number of lysine and arginine residues per mass of 35000.
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b8d246b5-e6ee-4dbc-9479-9195f300455c
| 1 |
The eight subunits are apparently arranged at the corners of a cube and therefore have dihedral (D4) symmetry. The bovine liver enzyme which has been cystallized contains 4--6 atoms of zinc per mole of enzyme. The apo-enzyme obtained on prolonged hydrolysis can be reactivated by the addition of zinc or cadmium ions.
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b8d246b5-e6ee-4dbc-9479-9195f300455c
| 2 |
The dialysed enzyme must be first treated with dithiothreitol. There are two very active SH groups in a total of 6--7-SH groups per subunit. The substrate forms a Schiff base with the epsilon-amino group of a lysine residue. Reduction of the Schiff base with NaBH4 should reveal the number of active sites per mole of enzyme.
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b8d246b5-e6ee-4dbc-9479-9195f300455c
| 3 |
It appears that only four of the eight subunits form a Schiff base with the substrate indicating that the enzyme exhibits the phenomenon of either half-site reactivity or negative cooperativity. The enzyme appears to have a strong subunit-subunit interaction for an immobilized preparation remained stable for at least a month.
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b8d246b5-e6ee-4dbc-9479-9195f300455c
| 4 |
An immobilized enzyme preparation was treated in a manner so that it dissociated into tetramers. Both the eluate and protein still attached to the Sepharose on a column were enzymically active. The bound enzyme could not reassociate under assay conditions but still contained about 50% of the original enzyme activity.
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b8d246b5-e6ee-4dbc-9479-9195f300455c
| 5 |
It would seem that the enzyme is active when composed with less than eight subunits.
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a0187a86-e770-423a-bf17-eee24c57d9bd
| 0 |
Mechanism and stereochemistry of enzymic reactions involved in porphyrin biosynthesis. 5-Aminolaevulinate synthetase cataylses the condensation of glycine and succinyl-CoA to give 5-aminolaevulinic acid. At least two broad pathways may be considered for the initial C--C bond forming step in the reaction. In pathway A the Schiff base of glycine and enzyme bound pyridoxal phosphate (a) undergoes decarboxylation to give the carbanion (b) which then condenses with succinyl-CoA with the retention of both the original C2 hydrogen atoms of glycine.
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a0187a86-e770-423a-bf17-eee24c57d9bd
| 1 |
In pathway B, loss of a C2 hydrogen atom gives another type of carbanion (c) that reacts with succinyl-CoA. Evidence has been presented to show that the initial C--C bond forming event occurs via pathway B which involves the removal of the pro R hydrogen atom of glycine.
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a0187a86-e770-423a-bf17-eee24c57d9bd
| 2 |
Subsequent mechanistic and stereochemical events occurring at the carbon atom destined to become C5 of 5-aminolaevulinate have also been delineated.(Carticle) Several mechanistic alternatices for the formation of the two vinyl groups of haem from the propionate residues of the precursor, coproporphyrinogen III, have been examined. (see article).
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a0187a86-e770-423a-bf17-eee24c57d9bd
| 3 |
It is shown that during the biosynthesis both the hydrogen atoms resident at the alpha positions of the propionate side chains remain undisturbed thus eliminating mechanisms which predict the involvement of acrylic acid intermediates. Biosynthetic experiments performed with precursors containing stereospecific labels have shown that the two vinyl groups of haem are formed through the loss of pro S hydrogen atoms from the beta-positions of the propionate side chains.
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a0187a86-e770-423a-bf17-eee24c57d9bd
| 4 |
In the light of these results, three related mechanisms for the conversion, propionate leads to vinyl, have been considered. In order to study the mechanism of porphyrinogen carboxy-lyase reaction, stereo-specifically deuterated, tritiated-succinate was incorporated into the acetate residues of uroporphyrinogen III which on decarboxylation generated asymmetric methyl groups in coproporphyrinogen III and then in haem.
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a0187a86-e770-423a-bf17-eee24c57d9bd
| 5 |
Degradation of the latter yielded chiral acetate deriving from C and D rings of haem. Configurational analysis of this derivate acetate shows that the carboxy-lyase reaction proceeds with a retention of configuration.
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15d39942-5555-4794-b498-9673568a2627
| 0 |
Biosynthesis of uroporphyrinogens from porphobilinogen: mechanism and the nature of the process. The enzymic self-polymerization of prophobilinogen gives rise to the cyclic tetrapyrroles uroporphyrinogen III and uroporphyrinogen I. The former is the precursor of all the natural porphyrins and chlorins. The formation of uroporphyrinogen III is catalysed by a dual enzymic system, porphobilinogen deaminase and uroporphyrinogen III cosynthase.
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15d39942-5555-4794-b498-9673568a2627
| 1 |
Deaminase polymerizes four porphobilinogen units on the enzymic surface, without liberation of free intermediates into the reaction medium, and forms uroporphyrinogen I. Cosynthase enters into association with the deaminase, and acts as a 'specifier protein' of the latter, changing the mode of porphobilinogen condensation on the enzymic surface.
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15d39942-5555-4794-b498-9673568a2627
| 2 |
The association is independent of the presence of substrate. While deaminase catalyses the head-to-tail condensation of the porphobilinogen units, the association deaminase-cosynthase catalyses the head-to-head condensation of the same units. As a result different enzyme-bound dipyrrylmethanes are formed form the beginning of the process, and this can be demonstrated by using synthetic dipyrrylmethanes and tripyrranes.
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5c1ffb0d-929e-4f66-ac0c-e3c9fb1ee88b
| 0 |
Biosynthesis of porphyrins and corrins. Haem, chlorophyll and vitamin B12 are all derived ultimately from four molecules of the pyrrole porphobilinogen (PBG) and the initial enzyme catalysed condensation of PBG leads to the unsymmetrical type III isomer of uroporphyrinogen. On the basis of straightforward chemical considerations the type I isomer should be formed and so the porphyrinogen-forming enzymes of all living systems must catalyse a highly specific rearrangement process.
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5c1ffb0d-929e-4f66-ac0c-e3c9fb1ee88b
| 1 |
The nature and chemical mechanism of this rearrangement poses one of the most fascinating problems in the porphyrin field and so it is not surprising that over 20 hypothetical schemes have been proposed to account for it. Analysis of the problem suggested that the incorporation of doubly 13C-labelled precursors into the rearranged macrocyclic rings would give valuable new information on the nature of the rearrangement process.
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5c1ffb0d-929e-4f66-ac0c-e3c9fb1ee88b
| 2 |
In this approach the meso=bridge atoms are of crucial importance, and several unambiguous syntheses of 13C-labelled pyrroles and porphyrins were developed to allow rigorous n.m.r. assignments to be made, and also to provide substrates for enzymic experiments. Studies carried out with enzymes from both avian blood and from Euglena gracilis have revealed the precise nature of the assembly of four PBG molecules into the type-III macrocycle:
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5c1ffb0d-929e-4f66-ac0c-e3c9fb1ee88b
| 3 |
it is the same in both systems despite their vastly different evolutionary development. Complementary studies are in progress in order to determine the intermediates involved in the conversion of PBG into uroporphyrinogen III. The synthesis of amino methyl pyrromethanes and their interaction in the presence of PBG with the appropriate enzyme systems are described.
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5c1ffb0d-929e-4f66-ac0c-e3c9fb1ee88b
| 4 |
It is important for the work to be able to separate not only isomeric pyrromethanes but also the four isomeric coproporphyrins. Powerful methods are described which make use of high pressure liquid chromatography for both types of separation process. Once uroporhyrinogen III has been built enzymically, there is a stepwise enzymic decarboxylation of the four acetic acid residues.
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5c1ffb0d-929e-4f66-ac0c-e3c9fb1ee88b
| 5 |
A heptacarboxylic porphyrin shown to be a type-III porphyrin is isolated from the action of avian blood enzymes on porphobilinogen. Spectroscopic studies with 13C-labelling limit the possible structures to two and total synthesis of these substances shows that the natural product carries its methyl group on ring D.
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5c1ffb0d-929e-4f66-ac0c-e3c9fb1ee88b
| 6 |
An isomeric heptacarboxylic porphyrin having its methyl group on ring C is of particular interest in relation to the biosynthesis of vitamin B12. This substance is synthesized together with uroporphyrin III, 14C-labelled specifically in ring C. This latter product is used to settle one of the key questions concerning nature's route to vitamin B12 - that is, does the corrin macrocycle arise from uroporphyrinogen III?
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5c1ffb0d-929e-4f66-ac0c-e3c9fb1ee88b
| 7 |
Incorporation studies and specific degradations prove specific incorporation of uroporphyrinogen III into cobyrinic acid, which is the known precursor of vitamin B12.
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fc6c9f97-9395-420e-aa7d-4563d83ee0cc
| 0 |
Synthesis of probable and improbable precursors for porphyrin biosynthesis. Insights into details of the biomechanism by which porphobilinogen (1) cyclotetramerizes to uroporphyrinogen III (2) as well as promising synthetic applications are provided by investigation of this reaction in vitro. The cyclotetramerization of newly prepared norporphobilinogen (5) proved to be extemely specific due to strong conformation control.
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fc6c9f97-9395-420e-aa7d-4563d83ee0cc
| 1 |
Advantage was taken of this finding by preparing a N,N,N,N-tetramethyl-porphyrinogen (13a) for the first time. Protected derivatives of the linear tetramer of porphobilinogen (20c) which is regarded as an intermediate of the cyclotetramerization were gained by total synthesis and their transformations investigated.
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a0df8ed7-6fc4-4b5a-9c3b-da2190aff35c
| 0 |
Macrocyclic intermediates in the biosynthesis of porphyrins. The hepta-, hexa- and penta-carboxylic porphyrins found in the faeces of rats poisoned with hexachlorobenzene have been separated by high-pressure liquid chromatography and characterized largely by spectroscopie methods. Their structures were confirmed by total synthesis, as part of a programme in which eleven of the fourteen hepta-, hexa- and penta-carboxylic porphyrins derived from uroporphyrin III have now been synthesized as their methyl esters.
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a0df8ed7-6fc4-4b5a-9c3b-da2190aff35c
| 1 |
The four isomeric heptacarboxylic and three of the pentacarboxylic porphyrinogens have been incubated with haemolysates of chicken erythrocytes, and they are all converted into protoporphyrin IX but at different rates. On the basis of this and other evidence we conclude that the decarboxylation of uroporphyrinogen III to coproporphyrinogen III is a stepwise process taking place by a preferred pathway (both in normal and abnormal metabolism);
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a0df8ed7-6fc4-4b5a-9c3b-da2190aff35c
| 2 |
the acetic acid groups are decarboxylated in a sequential clockwise fashion starting with that on the D ring and followed by those on the A, B and C rings. In the poisoned rats the uroporphyrinogen decarboxylase enzyme (or group of enzymes) is probably partially inhibited and the pentacarboxylic porphyrinogen with an acetic acid group on ring C accumulates.
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