Showing papers by "Rockefeller University published in 1978"
TL;DR: Using one embryonal carcinoma cell line, F9, it is found that retinoic acid at concentrations as low as 10(-9) M induces multiple phenotypic changes in the cultures in vitro, which are consistent with the proposition that retinosic acid induces differentiation of embryonal cancer cells into endoderm.
1,352 citations
TL;DR: These normative data for the intact rat can be directly compared to the taste reactivity of neurally ablated preparations which do not spontaneously feed or drink and can be utlized in determining the neural substrates necessary for the execution and regulation of ingestive behavior.
1,134 citations
TL;DR: Although rats without theta rhythm could not find their way directly to the goal, they recognized its location when they came upon it by chance, indicating a type of spatial deficit similar to that shown by hippocampally lesioned patient H.M.
Abstract: Rats learned, using distal room cues, to run to a goal on an elevated, circular track starting from any position on the track. The goal was one of eight equidistant, recessed cups set around the track, the goal cup being distinguished from the others solely by its position in the room. After learning, electrolytic lesions were made in the medial septal nucleus eliminating hippocampal theta rhythm in some animals but not in others. Rats without theta rhythm were no longer able to perform the spatial task, whereas rats with undisturbed theta rhythm retrained normal performance. Although rats without theta rhythm could not find their way directly to the goal, they recognized its location when they came upon it by chance. This type of spatial deficit appears similar to that shown by hippocampally lesioned patient H.M. Subsequent tests demonstrated that rats deprived of theta rhythm before training could nevertheless learn the task.
840 citations
TL;DR: The present results establish the existence of di-synaptic visceral afferent access to the highest autonomic integrative centers in the brain.
703 citations
TL;DR: Based on the similarities in the ingestion and rejection responses of decerebrate and intact rats, it appears that discriminative responses to taste result from integrative mechanisms complete within, or caudal to, the midbrain.
564 citations
TL;DR: In this article, an analysis of adipose tissue morphology changes during the course of diet-induced weight gain suggests that the achievement of some specific mean adipocyte size triggers the events that culminate in adipocyte number increase.
Abstract: Adult rats of various strains became obese when they were fed a highly palatable diet for several months. Analysis of their adipose tissue morphology revealed increases in both adipocyte size and number in most depots. Reintroduction of an ordinary chow diet to such animals precipitated a period of weight loss during which only mean adipocyte size returned to normal. Adipocyte number remained at the elevated level achieved during the period of weight gain. Thus, transient dietary obesity in rats results in a persistent obesity of a purely hyperplastic, nonhypertrophic form. Furthermore, the persistence of the cell number increase suggests that it is the result of proliferation or differentiation rather than of only an increase in the lipid content of a pool of very small and normally undetected adipocytes. An analysis of adipose tissue morphology changes during the course of diet-induced weight gain suggests that the achievement of some specific mean adipocyte size triggers the events that culminate in adipocyte number increase. What mechanisms may link adipocyte size to the formation of new adipocytes remains unknown.
492 citations
TL;DR: These studies suggest that this cross-stimulation results from the intercellular communication of a mediator that is common to both cell types and the communicated mediator may be cyclic AMP.
Abstract: Rat ovarian granulosa cells and mouse myocardial cells respond to cell-specific hormones by cyclic AMP-dependent mechanisms. In coculture, these heterologous cells communicate by means of gap junctions. Exposure of the cocultures to a hormone specific for one cell type causes the heterologous cells to respond through a cell contact-dependent mechanism. These studies suggest that this cross-stimulation results from the intercellular communication of a mediator that is common to both cell types. The communicated mediator may be cyclic AMP.
473 citations
TL;DR: Results from other studies converge on the medial PVN region as being a key link in the process of increased food and water consumption associated with increased noradrenergic activity.
Abstract: Central injection of norepinephrine (NE) has been found to elicit preprandial drinking and feeding responses in the satiated rat. In the present study, 35 different brain areas, in over 500 rats, were examined to localize the precise region of NE sensitivity. Essentially all sites outside the hypothalamus, as well as in the lateral portion of the hypothalamus, were relatively or totally unresponsive to NE. In the medial hypothalamic area, the paraventricular nucleus (PVN) was clearly distinguished as the most effective site for initiating both feeding and drinking with noradrenergic activation in the satiated animal. Sites greater than 0.5 mm rostral, caudal, dorsal, ventral or lateral to this nucleus yielded significantly smaller effects. In mildly hungry rats, NE was found to potentiate the ongoing feeding response, and anatomical analyses of this phenomenon showed the PVN to be most responsive, with a smaller but reliable potentiation occurring along the periventricular hypothalamus adjacent to the third ventricle. Norepinephrine injected into the lateral perifornical hypothalamic area actually produced a suppression of feeding in these hungry animals. These findings, together with results from other studies, converge on the medial PVN region as being a key link in the process of increased food and water consumption associated with increased noradrenergic activity.
445 citations
TL;DR: A high glucose concentration in vivo or an increased glucose of glucose 6-phosphate concentration in vitro has been found to lead to the glycosylation of epsilon-amino groups of lysine residues in bovine and rat lens crystallins, suggesting a new interpretation of previous results on cataract formation and a new approach for development of drugs to prevent cataracts.
Abstract: A high glucose concentration in vivo or an increased glucose of glucose 6-phosphate concentration in vitro has been found to lead to the glycosylation of epsilon-amino groups of lysine residues in bovine and rat lens crystallins. In vitro, this glycosylation imparts an increased susceptibility of the crystallins to sulfhydryl oxidation. Disulfide crosslinks result in the formation of high molecular weight aggregates and an opalescence in the crystallin solutions. The addition of reducing agents prevents as well as reverses the formation of high molecular weight aggregates and the opalescence of the crystallins. These phenomena suggest a new interpretation of previous results on cataract formation and a new approach for development of drugs to prevent cataracts.
416 citations
TL;DR: The results suggest that Japanese macaques engage left-hemisphere processors for the analysis of communicatively significant sounds that are analogous to the lateralized mechanisms used by humans listening to speech.
Abstract: Five Japanese macaques and five other Old World monkeys were trained to discriminate among field-recorded Japanese macaque vocalizations. One task required discrimination of a communicatively relevant acoustic feature ("peak"), and a second required discrimination of an orthogonal feature of the same vocalizations ("pitch"). The Japanese animals more proficiently discriminated the peak feature when stimuli were presented to the right ear (primarily left cerebral hemisphere), as opposed to the left ear (primarily right hemisphere). In discriminating the pitch feature, the Japanese animals either showed (i) a left-ear processing advantage or (ii) no ear advantage. The comparison animals, with one exception, showed no ear advantage in processing either feature of the vocalizations. The results suggest that Japanese macaques engage left-hemisphere processors for the analysis of communicatively significant sounds that are analogous to the lateralized mechanisms used by humans listening to speech.
412 citations
TL;DR: Food-deprived decerebrate rats, like intact ones, ingested a taste substance they had rejected when sated, but these same decerebrates neither rejected nor decreased ingestive reactions to a novel taste after that taste had been repeatedly paired with lithium chloride-induced illness.
Abstract: Taste substances applied to the oral cavity result in either ingestion or rejection, each with a characteristic muscular response pattern. These responses are the same in decerebrate and intact rats; the caudal brainstem appears to be the neural substrate of ingestion and rejection responses. The experiment determined whether decerebrates can alter these discriminative responses as a function of food deprivation or toxicosis. Food-deprived decerebrate rats, like intact ones, ingested a taste substance they had rejected when sated. However, these same decerebrates, in contrast to controls, neither rejected nor decreased ingestive reactions to a novel taste after that taste had been repeatedly paired with lithium chloride-induced illness. Although the forebrain may be important for integrating ingestion, some aspects of this control seem to be represented in caudal brain areas.
TL;DR: Work from the laboratory indicates that, in the rat brain, there are in fact two anatomically distinct progestin receptor systems, one of which differs strikingly from the systems identified previously in neural and non-neural tissues in that it is apparently insensitive to oestrogen.
Abstract: IT is now well established that progesterone can either facilitate or inhibit the effects of oestrogen on gonadotrophin release and behaviour1. Whether facilitation or inhibition is observed depends primarily on the time interval between exposure to oestrogen and progesterone, but the mechanism by which progesterone exerts these effects remains unknown. Attempts to demonstrate progesterone receptor sites within the brain and pituitary have given equivocal results2–10, leading to speculation that the central effects of progesterone may be mediated through a mechanism fundamentally different from that found in peripheral tissues1,2,6. More recently, however, several studies have suggested that oestrogen-inducible progestin receptor systems similar to those found in peripheral progesterone target tissues can be identified in the brain and pituitary if sufficiently sensitive and specific experimental procedures are used11–14. We summarise here work from our laboratory which indicates that, in the rat brain, there are in fact two anatomically distinct progestin receptor systems, one of which differs strikingly from the systems identified previously in neural and non-neural tissues in that it is apparently insensitive to oestrogen.
TL;DR: These data on conservation of the Ad2 sequences suggest that each transcriptional event from the 16-99 transcription unit gives rise to one of a possible 13-14 mRNA molecules with destruction of the remainder of the transcribed RNA.
TL;DR: Strong homologies at cap sites and splice points suggest that for the noted cases, the virus and cell share closely related mechanisms for mRNA 5' end synthesis and splicing.
TL;DR: Together, these results demonstrate that the in vitro reconstruction of the post-translational transport of the higher plant precursors is physiologically significant.
Abstract: A precursor to the small subunit of ribulose-1,5-bisphosphate carboxylase [3-phospho-D-glycerate carboxylyase (dimerizing), EC 4.1.1.39] has been identified among the products of cell-free translation of polyadenylated RNA from spinach and pea. In both cases, the precursor is larger than the mature protein by 4000-5000 daltons. Upon incubation of post-ribosomal supernatants of the in vitro protein synthesis mixtures with purified intact chloroplasts, the pea and spinach precursors are transported interchangeably into the chloroplasts and processed to the mature size and charge. Moreover, the newly transported small subunits are found to assemble with endogenous large subunits to form the holoenzyme. In contrast, a precursor to the Chlamydomonas reinhardtii small subunit is not taken up by higher plant chloroplasts, indicating the specificity of the transport events. Together, these results demonstrate that the in vitro reconstruction of the post-translational transport of the higher plant precursors is physiologically significant.
TL;DR: The recently discovered noncontiguous sequences in eukaryotic DNA that encode messenger RNA may reflect an ancient, rather than a new, distribution of information in DNA and that eukARYotes evolved independently of prokaryotes.
Abstract: The differences in the biochemistry of messenger RNA formation in eukaryotes compared to prokaryotes are so profound as to suggest that sequential prokaryotic to eukaryotic cell evolution seems unlikely. The recently discovered noncontiguous sequences in eukaryotic DNA that encode messenger RNA may reflect an ancient, rather than a new, distribution of information in DNA and that eukaryotes evolved independently of prokaryotes.
TL;DR: The erythrocytic cycle of the human malaria parasite, Plasmodium, falciparum, was examined by electron microscopy and the time of appearance of knobs on cells in vitro correlates with the life cycle stage of parasites which are sequestered from the peripheral circulation in vivo.
Abstract: SYNOPSIS. The erythrocytic cycle of the human malaria parasite, Plasmodium falciparum, was examined by electron microscopy. Three strains of parasites maintained in continuous culture in human erythrocytes were compared with in vivo infections in Aotus monkeys. The ultrastructure of P. falciparum is not altered by continuous cultivation in vitro. mitochondria contain DNA-like filaments and some cristae at all stages of the erythrocytic life cycle. The Golgi apparatus is prominent at the schizont stage and may be involved in the formation of rhoptries. In culture, knob-like protrusions first appear on the surface of trophozoite-infected erythrocytes. The time of appearance of knobs on cells in vitro correlates with the life cycle stage of parasites which are sequestered from the peripheral circulation in vivo. Knob material of older parasites coalesces and forms extensions from the erythrocyte surface. Some of this material is sloughed from the host cell surface. The parasitophorous vacuole membrane breaks down in erythrocytes containing mature merozoites both in vitro and in vivo. Merozoite structure is similar to that of P. knowlesi. The immature gametocytes in culture have no knobs.
TL;DR: A new class of two-dimensional random textures with identical third-order statistics that can be effortlessly discriminated is found, and it is commonly assumed that texture granularity is determined by the power spectrum, but this is not the case.
Abstract: We found a new class of two-dimensional random textures with identical third-order statistics that can be effortlessly discriminated. Discrimination is based on local "granularity" differences between these iso-trigon texture pairs. This is the more surprising since it is commonly assumed that texture granularity (grain) is determined by the power spectrum which, in turn, can be obtained from the second-order statistics. Because textures with identical third-order statistics must have identical second-order statistics (i.e., identical power spectra), visible texture granularity is not controlled by power spectra, and not even by third-order statistics.
TL;DR: The method for continuous cultivation of Plasmodium falciparum has now been successfully applied to several strains from different geographical areas and has been used for tests of antimalarial drugs, studies of parasite–host cell interactions with special reference to sickle haemoglobin, and for the production of amounts of parasite material sufficient for experimental immunisation of Aotus trivirgatus monkeys.
Abstract: The method for continuous cultivation of Plasmodium falciparum has now been successfully applied to several strains from different geographical areas. It has been used for tests of antimalarial drugs, for studies of parasite-host cell interactions with special reference to sickle haemoglobin, and for the production of amounts of parasite sufficient for experimental immunisation of Aotus trivirgatus monkeys.
TL;DR: In this paper, the authors explore the possibility that particular animals may experience thoughts and feelings of one sort or another under various conditions, and explore whether or not the differences between men and animals in this respect are qualitative and absolute.
Abstract: What, if anything, do animals think about? Do they have anything at all comparable to mental experiences as we know them? Are any of them ever aware of themselves, their surroundings, or the results likely to follow from their behavior? It would of course be manifestly absurd to overlook or underestimate the enormous differences in complexity, versatility, and range of comprehension between human and animal thinking (if the latter occurs at all). However, our direct knowledge of our own mental experiences, imperfect as it may be, is apparently quite sufficient to establish the importance of such experiences, at least in one species. Mental experiences will not wither away merely to keep science simple and tidy. Hence it is appropriate to inquire whether or not the differences between men and animals in this respect are qualitative and absolute, and to explore the possibility that particular animals may experience thoughts and feelings of one sort or another under various conditions. Determining the nature and extent of animal thinking is crucially important in our attempt to understand human uniqueness and our place in the universe, as has been discussed by Popper and Eccles (1977) and many others.
TL;DR: Present HRP data suggest that the cells of origin of spinothalamic tract fibers were situated in laminae IV, V, and VI, as well as the location of spinal cord cells oforigin of additional ascending tracts.
TL;DR: The available evidence suggests that the synthesis of polypeptide 4 requires “early” protein synthesis, which is distinct from the eight defined influenza virus gene products.
01 Jan 1978
TL;DR: The histochemical demonstration of nonspecific acid α-naphthyl acetate esterase (ANAE) activity was evaluated as a T lymphocyte marker primarily with the sheep erythrocyte (E) assay, and a distinctive staining pattern characterized T lymphocytes which could be readily distinguished from monocytes.
TL;DR: Observations in cats show that receptor properties and/or spinal mechanisms involved in the stretch reflex are sufficient to produce a segmented response similar to that observed in intact animals.
Abstract: A sudden and rapid angular displacement of the limb evokes, in human and monkey subjects, a segmented pattern of electromyographic activity in muscles which are stretched. While the first segment is acknowledged to represent a tendon jerk, it has been proposed that the second segment, occurring with a shorter latency than a reaction time, is mediated by a transcortical loop. The present experiments were conducted in cats to determine the properties of muscle responses to torque perturbations analogous to those used in the monkey, and to determine if the integrity of supraspinal pathways is required for the individual response segments to occur. Torque perturbations which flexed the forearm evoked a segmented response in the electromyogram of the cat triceps muscle. This response typically consisted of three early segments with latencies of 10, 30 and 60 msec which were similar to the M1, M2, and M3 segments described in the monkey. The M3 and occasionally M2 components were depressed when the cat followed rather than resisted the perturbation. A torque pulse of 10 msec duration was sufficient to elicit a near maximal M1 response while torque pulses in excess of 20 msec were required to evoke the M2 response. To determine if any of these components required mediation by the cerebral cortex, experiments were conducted in decerebrate and spinal cats. Similar torque perturbations produced segmented electromyographic responses in the triceps muscles which were indistinguishable in their timing from those observed in intact cats. The torque required to produce the segmented responses was comparable as well. All three segments were dependent upon the activation of receptors in the homonymous muscle and did not require cutaneous input. These observations show that receptor properties and/or spinal mechanisms involved in the stretch reflex are sufficient to produce a segmented response similar to that observed in intact animals.
TL;DR: The observations suggest that cats were capable of making rapid and accurate adjustments in the force they applied to a lever in accord with information provided by a compensatory display and were determined by a pulse-step control policy.
Abstract: In the previous study it was shown that cats were capable of making rapid and accurate adjustments in the force they applied to a lever in accord with information provided by a compensatory display. In the present study, isometric responses were examined in greater detail to determine 1. if a general control policy (or model) governing responses of different magnitudes could be inferred from the relations among output parameters and 2. if the earliest output measures were scaled to the preceding sensory events. The force adjustments elicited by the sudden motion of the display showed a linear relation between the peak force and the peak of its first derivative, dF/dt. Similarly, the peak d2F/dt2 was a linear function of dF/dt. By contrast, the times required to achieve the peak force and the peak dF/dt were largely independent of their magnitudes. These adjustments were produced by a burst of EMG activity in agonist muscles which coincided with the rising phase of dF/dt. The observations suggest that such motor outputs are determined by a pulse-step control policy. The amplitude of the pulse would control the rate of rise of dF/dt (and therefore also the peak force since the rising phase of dF/dt was of constant duration), and the step would control the level of the terminal steady state force. Both the peak force and the preceding peak dF/dt were highly correlated with the amplitude of the perturbation. Changes in display gain, which altered the required relation between input and output magnitudes, resulted in a gradual readjustment of the output parameters. It was concluded that the motor outputs were scaled from their inception to requirements dictated by the initial sensory information. The selection by the cat of the appropriate scaling function was contingent upon its previous experience with the device.
TL;DR: Investigations of the cellular and viral biosynthesis, in which compounds in this class of benzimidazoles possess the unique biological activity of selective inhibition of the synthesis of nuclear heterogeneous RNA, are reviewed.
Abstract: Publisher Summary This chapter brings together in a systematic way the recent work as well as some of the earlier studies on the mode of action of halogenated ribofuranosylbenzimidazoles on cellular and viral biosynthesis. Investigations of the cellular and viral biosynthesis, in which these compounds have been used as exploratory tools are also reviewed in this chapter. Compounds in this class of benzimidazoles possess the unique biological activity of selective inhibition of the synthesis of nuclear heterogeneous RNA (hnRNA) in cells of cold-blooded animals, including insects and in cells of avian and mammalian species. Because of the universality of the synthesis of hnRNA in animal species and because a portion of hnRNA sequences becomes mRNA, the action of halobenzimidazole ribosides on cellular biosynthesis is of broad interest. The action of these derivatives is also relevant to the process of transcription of the viral genomes of certain RNA and DNA viruses. In addition, this chapter briefly discusses three groups of structurally distinct bcnzimidazolcs that possess biological actions entirely different from those of halobenzimidazole ribosides: 2-(α-hydroxybenzyl) benzimidazole and certain related compounds are selective inhibitors of picornavirus multiplication; 5-methyl-2-D-ribobenzimidazole and congeners and 5-hydroxy-l-methylbenzimidazole and certain related compounds restore the capacity of chorioallantoic membranes from older chicken embryos to produce influenza virus in high yield.
TL;DR: In this paper, it was shown that the problem of natural suppression of strong $P$ and $T$ noninvariances in the presence of instantons may be resolved without invoking symmetries which imply massless quarks or nearly massless bosons.
Abstract: We show, by explicit construction of a highly convergent superweak theory of $\mathrm{CP}$ nonconservation, that the problem of natural suppression of strong $P$ and $T$ noninvariances---in the presence of instantons---may be resolved without invoking symmetries which imply massless quarks or nearly massless bosons.
TL;DR: RmRNA from rat mammary glands 13-15 days post partum was translated in a wheat germ cell-free system either in the absence or in the presence of ribosome-denuded membranes prepared from isolated rough microsomes of dog pancreas.
Abstract: mRNA from rat mammary glands 13-15 days post partum was translated in a wheat germ cell-free system either in the absence or in the presence of ribosome-denuded membranes prepared from isolated rough microsomes of dog pancreas. Newly synthesized α-lactalbumin was identified by immunoprecipitation with a monospecific rabbit antiserum against rat α-lactalbumin and was characterized by partial amino-terminal sequence determination and by lectin affinity chromatography. In the absence of membranes a presumably unglycosylated form of α-lactalbumin was synthesized that bound neither to concanavalin A-Sepharose nor to Ricinus communis lectin-agarose and that contained an amino-terminal signal peptide region comprising 19 amino acid residues. In the presence of membranes a processed form was synthesized that lacked the signal peptide portion and that had an amino-terminal sequence identical to that of mature α-lactalbumin. Furthermore, this processed form was found to be segregated, presumably within the microsomal vesicles, because it was resistant to post-translational proteolysis. It was also found to be glycosylated, and because it bound to concanavalin A-Sepharose, from which it could be eluted specifically by α-methyl mannoside, but not to R. communis lectin-agarose, it was presumably core-glycosylated. Processing, segregation, and core glycosylation were observed to proceed only when membranes were present during translation and not when they were added after translation.
TL;DR: The present study summarizes some statistics that seem relevant to addiction that have been admitted to methadone maintenance programs in New York since the modality was formally defined in 1%5.
Abstract: The root causes of narcotic addiction are unknown. Contributory factorssuch as easy availability of drugs, peer group delinquency, broken families, and adolescent curiosity,-of course are statistically associated with addiction since they are correlated with exposure, but they d o not explain why, with apparently equal exposure, some persons become life-long addicts while others d o not. Why do many adolescents use narcotics a few times and then reject the habit, while a minority become chronic drug-dependent users? Why d o some of the persons who start with narcotics quit the drug after a few months of heavy use? How can some persons remain occasional users while others progress to intractable, life-destroying addiction with narcotic drugs dominating all other interests? Are the social, psychological and medical disabilities seen in chronic addicts the causes of addiction or d o they simply reflect the unhealthy life that addicts lead? How often can chronic addiction to narcotics be cured by a program that provides motivation and promotes social rehabilitation? Can success be predicted? The present study summarizes some statistics that seem relevant to these questions. The problem of addiction obviously goes deeper than the environment. If narcotic drugs serve only as a n escape from bad living conditions, a maintenance program should become unnecessary when the subjects have a job, a stable family and a sense of accomplishment. But experience teaches differently. Most persons with a long history of heroin use relapse after detoxification whether or not they had been rehabilitated. Their relapses might be ascribed to residual psychopathology, to the persistence of conditioned reflexes or t o some undefined metabolic disease-but these are only conjectures, and certainly not worth fighting about. The practical fact is that some heroin users can become permanently abstinent, while others relapse, even under the best conditions. How can we predict the outcome? One factor in prediction obviously is the duration of use. Even without treatment, most short-term users stop using narcotics and move to other interests. Time is selective. After the experimenters have left the field, we see the chronic users. When addiction has persisted for several years despite efforts a t dissuasion by punishment and treatment, the probability of a spontaneous remission becomes much less. It is this intractable group that we have treated in the methadone maintenance programs. They are the subjects of the present report. Approximately 82,000 addicts have been admitted to methadone maintenance programs in New York since the modality was formally defined in 1%5. All are listed in the files of the Community Treatment Foundation which has maintained