Showing papers in "Science in 1977"
TL;DR: A biopsychosocial model is proposed that provides a blueprint for research, a framework for teaching, and a design for action in the real world of health care.
Abstract: The dominant model of disease today is biomedical, and it leaves no room within tis framework for the social, psychological, and behavioral dimensions of illness. A biopsychosocial model is proposed that provides a blueprint for research, a framework for teaching, and a design for action in the real world of health care.
8,359 citations
5,833 citations
TL;DR: A rapid, direct method for screening single plaques of Agt recombinant phage is described, which allows at least 10(6) clones to be screened per day and simplifies physical containment of recombinants.
Abstract: A rapid, direct method for screening single plaques of Agt recombinant phage is described. The method allows at least 10(6) clones to be screened per day and simplifies physical containment of recombinants.
3,922 citations
TL;DR: First-order nonlinear differential-delay equations describing physiological control systems displaying a broad diversity of dynamical behavior including limit cycle oscillations, with a variety of wave forms, and apparently aperiodic or "chaotic" solutions are studied.
Abstract: First-order nonlinear differential-delay equations describing physiological control systems are studied. The equations display a broad diversity of dynamical behavior including limit cycle oscillations, with a variety of wave forms, and apparently aperiodic or "chaotic" solutions. These results are discussed in relation to dynamical respiratory and hematopoietic diseases.
3,839 citations
TL;DR: Observations by infrared transillumination in the exposed heart and in the brain in cephalo without surgical intervention show that oxygen sufficiency for cytochrome a,a3, function, changes in tissue blood volume, and the average hemoglobin-oxyhemoglobin equilibrium can be recorded effectively and in continuous fashion for research and clinical purposes.
Abstract: The relatively good transparency of biological materials in the near infrared region of the spectrum permits sufficient photon transmission through organs in situ for the monitoring of cellular events. Observations by infrared transillumination in the exposed heart and in the brain in cephalo without surgical intervention show that oxygen sufficiency for cytochrome a,a3, function, changes in tissue blood volume, and the average hemoglobin-oxyhemoglobin equilibrium can be recorded effectively and in continuous fashion for research and clinical purposes. The copper atom associated with heme a3 did not respond to anoxia and may be reduced under normoxic conditions, whereas the heme-a copper was at least partially reducible.
3,725 citations
TL;DR: Infants between 12 and 21 days of age can imitate both facial and manual gestures; this behavior cannot be explained in terms of either conditioning or innate releasing mechanisms.
Abstract: Infants between 12 and 21 days of age can imitate both facial and manual gestures; this behavior cannot be explained in terms of either conditioning or innate releasing mechanisms. Such imitation implies that human neonates can equate their own unseen behaviors with gestures they see others perform.
2,904 citations
2,515 citations
2,281 citations
TL;DR: A hypothetical model of the active site of angiotensin-converting enzyme, based on known chemical and kinetic properties of the enzyme, has enabled a new class of potent and specific inhibitors, carboxyalkanoyl and mercaptoalkanoysl derivatives of proline, to be designed.
Abstract: A hypothetical model of the active site of angiotensin-converting enzyme, based on known chemical and kinetic properties of the enzyme, has enabled us to design a new class of potent and specific inhibitors. These compounds, carboxyalkanoyl and mercaptoalkanoyl derivatives of proline, inhibit the contractile response of guinea pig ileal strip to angiotensin I and augment its response to bradykinin. When administered orally to rats, these agents inhibit the pressor effect of angiotensin I, augment the vasodepressor effect of bradykinin, and lower blood pressure in a model of renovascular hypertension.
1,759 citations
TL;DR: The data support the proposition that the latency of P300 corresponds to stimulus evaluation time and is independent of response selection.
Abstract: A technique for measuring the latency of the P300 component of event-related brain potentials on individual trials is described. Choice reaction times and the latency of the P300 were compared under speed-maximizing and under accuracy-mazimising instructions. The choice stimuli required different levels of semantic categorization. The data support the proposition that the latency of P300 corresponds to stimulus evaluation time and is independent of response selection.
1,671 citations
Journal Article•
TL;DR: Competition for the receptor by various benzodiazepines closely parallels their pharmacological potency, and binding to the receptor is stereospecific.
Abstract: Diazepam, a potent minor tranquilizer, binds with high affinity to a specific benzodiazepine receptor that occurs exclusively in the central nervous system. The receptor is mainly localized in the synaptic membrane fraction. Binding to the receptor is stereospecific. Competition for the receptor by various benzodiazepines closely parallels their pharmacological potency.
TL;DR: Three-month-old rats were injected intraperitoneally with [3H]thymidine and labeled cells in the granular layers of dentate gyrus and olfactory bulb were confirmed as neurons by electron microscopy of reembedded 1-micrometer sections.
Abstract: Three-month-old rats were injected intraperitoneally with [3H]thymidine (4.3 microcuries per gram of body weight) and allowed to survive for 30 days. Radioautography of 1-micrometer sections revealed labeled cells in the granular layers of dentate gyrus and olfactory bulb; these were confirmed as neurons by electron microscopy of reembedded 1-micrometer sections.
TL;DR: Clones derived in vitro from a parent culture of murine malignant melanoma cells varied greatly in their ability to produce metastatic colonies in the lungs upon intravenous inoculation into syngeneic mice suggests that the parent tumor is heterogeneous and that highly metastatic tumor cell variants preexist in the parental population.
Abstract: Clones derived in vitro from a parent culture of murine malignant melanoma cells varied greatly in their ability to produce metastatic colonies in the lungs upon intravenous inoculation into syngeneic mice. This suggests that the parent tumor is heterogeneous and that highly metastatic tumor cell variants preexist in the parental population.
TL;DR: In vitro analysis of the kinetic isotope effects of this reaction indicates that there will be a large, temperature-dependent difference in the carbon-13/carbon-12 ratio between the methyl and carbonyl carbon atoms of acetyl coenzyme A and between thosecarbon atoms of lipid components which derive from them.
Abstract: The low carbon-13/carbon-12 ratio of lipids is shown to result from isotopic fractionation during the oxidation of pyruvate to acetyl coenzyme A. In vitro analysis of the kinetic isotope effects of this reaction indicates that there will be a large, temperature-dependent difference in the carbon-13/carbon-12 ratio between the methyl and carbonyl carbon atoms of acetyl coenzyme A and between those carbon atoms of lipid components which derive from them.
TL;DR: Both hormones possess common and identical regulatory mechanisms and there may be a functional role for circulating beta-endorphin in response to acute stress or long-term adrenalectomy.
Abstract: The opiate-like peptide beta-endorphin and adrenocorticotropin are concomitantly secreted in increased amounts by the adenohypophysis in response to acute stress or long-term adrenalectomy as well as in vitro in response to purified corticotropin releasing factor and other secretagogues. Conversely, administration of the synthetic glucocorticoid dexamethasone inhibits the secretion of both adrenocorticotropin and beta-endorphin. Thus, both hormones possess common and identical regulatory mechanisms and there may be a functional role for circulating beta-endorphin.
TL;DR: The findings indicate that glia have a crucial role in glutamic acid, gamma-aminobutyric acid, and ammonia metabolism in brain.
Abstract: Light microscopy immunohistochemical techniques were used to examine the distribution of glutamine synthetase in rat brain. Glutamine synthetase was found to be localized in the glial cells. Neuronal cell bodies, endothelial cells, and choroid epithelium contained no enzyme. The findings indicate that glia have a crucial role in glutamic acid, gamma-aminobutyric acid, and ammonia metabolism in brain.
TL;DR: Recombinant bacterial plasmids have been constructed that contain complementary DNA prepared from rat islets of Langerhans messenger RNA that contain cloned sequences representing the complete coding region of rat proinsulin I, part of the preproinsulin II prepeptide, and the untranslated 3' terminal region of the mRNA.
Abstract: Recombinant bacterial plasmids have been constructed that contain complementary DNA prepared from rat islets of Langerhans messenger RNA. Three plasmids contain cloned sequences representing the complete coding region of rat proinsulin I, part of the preproinsulin I prepeptide, and the untranslated 3' terminal region of the mRNA. A fourth plasmid contains sequences derived from the A chain region of rat preproinsulin II.
TL;DR: The results suggest that adriamycin has at least two mechanisms of tissue damage: one, which involves lipid peroxidation, is blocked by tocopherol and results in cardiac toxicity; the other, which consists of binding to DNA, is not antagonized by toCophero and is responsible for tumor response.
Abstract: The antitumor antibiotic, adriamycin, induces severe cardiac toxicity associated with peroxidation of cardiac lipids in mice. Both this lipid peroxidation and cardiac toxicity of adriamycin are reduced by prior treatment of the animals with the free radical scavenger tocopherol. Such treatment with tocopherol does not, however, alter the magnitude or duration of the adriamycin-induced suppression of DNA synthesis in P388 ascites tumor, nor does it diminish the antitumor responsiveness of P388 ascites tumor. These results suggest that adriamycin has at least two mechanisms of tissue damage: one, which involves lipid peroxidation, is blocked by tocopherol and results in cardiac toxicity; the other, which involves binding to DNA, is not antagonized by tocopherol and is responsible for tumor response.
TL;DR: A cardioexcitatory substance from ganglia of the clam Macrocallista nimbosa, formerly designated peak C, is the tetrapeptide amide Phe-Met-Arg-Phe-NH2, which is active at about 10(-8)M when assayed on molluscan muscle.
Abstract: A cardioexcitatory substance from ganglia of the clam Macrocallista nimbosa, formerly designated peak C, is the tetrapeptide amide Phe-Met-Arg-Phe-NH2. Its structure was determined by the combined use of Edman dansyl degradation and tryptic digestion. The structure was confirmed by synthesis. This neuropeptide is active at about 10(-8)M when assayed on molluscan muscle.
TL;DR: Chronic treatment of rats with the neuroleptic drugs haloperidol, fluphenazine, and reserpine elicits a 20 to 25% increase in striatal dopamine receptor binding assayed with [3H]haloperidols, which may account for behavioral supersensitivity to dopamine receptor stimulants in such animals and for tardive dyskinesia in patients treated with these drugs.
Abstract: Chronic treatment of rats with the neuroleptic drugs haloperidol, fluphenazine, and reserpine elicits a 20 to 25% increase in striatal dopamine receptor binding assayed with [3H]haloperidol. This increase in receptor sites may account for behavioral supersensitivity to dopamine receptor stimulants in such animals and for tardive dyskinesia in patients treated with these drugs.
TL;DR: This work has reported the first synthesis of a functional polypeptide product from a gene of chemically synthesized origin, including the sequence of amino acids corresponding to somatostatin, in vitro.
Abstract: A gene for somatostatin, a mammalian peptide (14 amino acid residues) hormone, was synthesized by chemical methods. This gene was fused to the Escherichia coli beta-galactosidase gene on the plasmid pBR322. Transformation of E. coli with the chimeric plasmid DNA led to the synthesis of a polypeptide including the sequence of amino acids corresponding to somatostatin. In vitro, active somatostatin was specifically cleaved from the large chimeric protein by treatment with cyanogen bromide. This represents the first synthesis of a functional polypeptide product from a gene of chemically synthesized origin.
TL;DR: Kuru established that virus infections of man could, after long delay, produce chronic degenerative disease and disease with apparent heredofamilial patterns of occurrence, and with none of the inflammatory responses regularly associated with viral infections.
Abstract: Kuru was the first chronic degenerative disease of man shown to be a slow virus infection, with incubation periods measured in years and with a progressive accumulative pathology always leading to death. This established that virus infections of man could, after long delay, produce chronic degenerative disease and disease with apparent heredofamilial patterns of occurrence, and with none of the inflammatory responses regularly associated with viral infections. Soon thereafter, several other progressive degenerative diseases of the brain were likewise attributed to slow virus infections (see Tables 1 and 2). These include delayed and slow measles encephalitis, now usually called subacute sclerosing panencephalitis (SSPE), progressive multifocal leukoencephalopathy (PML), and transmissible virus dementias usually of the Creutzfeldt-Jakob disease (CJD) type. Thus, slow virus infections, first recognized in animals, became recognized as a real problem in human medicine. Kuru has led us, however, to a more exciting frontier in microbiology than only the demonstration of a new mechanism of pathogenesis of infectious disease, namely the recognition of a new group of viruses possessing unconventional physical and chemical properties and biological behavior far different from those of any other group of microorganisms. However, these viruses still demonstrate sufficiently classical behavior of other infectious microbial agents for us to retain, perhaps with misgivings, the title of “viruses”. It is about these unconventional viruses that I would further elaborate. The group consists of viruses causing four known natural diseases: two of man, kuru and CJD, and two of animals, scrapie in sheep and goats, and transmissible mink encephalopathy (TME) (Table 1). The remarkable unconventional properties of these viruses are summarized in Tables 3 and 4. Because only primate hosts have been available as indicators for the viruses
TL;DR: Three of the Charon vector phages, 3A, 4A, and 16A, have been certified for use as EK2 vector-host systems, when propagated in bulk in a special bacterial host, DP50SupF.
Abstract: The Charon lambda bacteriophages have been developed as vectors for cloning. Their construction incorporates mutations that make them simple to use and also greatly increases their safety for the biological containment of cloned recombinant DNA. Three of the Charon vector phages, 3A, 4A, and 16A, have been certified for use as EK2 vector-host systems, when propagated in bulk in a special bacterial host, DP50SupF. We present here some of the data on which the safety of these systems was evaluated. DNA fragments ranging in size from 0 to 2.2 X 10(4) base pairs can be cloned in these EK2 Charon phages.
TL;DR: The development at age 10 of the ability to encode orientation-specific configurational aspects of a face may reflect completion of certain maturational changes in the right cerebral hemisphere.
Abstract: Unlike older children and adults, children of less than about 10 years of age remember photographs of faces presented upside down almost as well as those shown upright and are easily fooled by simple disguises. The development at age 10 of the ability to encode orientation-specific configurational aspects of a face may reflect completion of certain maturational changes in the right cerebral hemisphere.
TL;DR: The results suggest that satisfactory alleviation of persistent pain in humans may be obtained by electronic stimulation.
Abstract: Relief of intractable pain was produced in six human patients by stimulation of electrodes permanently implanted in the periventricular and periaqueductal gray matter. The level of stimulation sufficient to induce pain relief seems not to alter the acute pain threshold. Indiscriminate repetitive stimulation produced tolerance to both stimulation-produced pain relief and the analgesic action of narcotic medication; this process could be reversed by abstinence from stimulation. Stimulation-produced relief of pain was reversed by naloxone in five out of six patients. These results suggest that satisfactory alleviation of persistent pain in humans may be obtained by electronic stimulation.
TL;DR: The binding of [3H]haloperidol to rat striatal dopamine receptors increases after lesion (made by injection of 6-hydroxydopamine) of the nigrostriatal dopamine pathway in those rats which are behaviorally supersensitive, as reflected by apomorphine-induced contralateral rotations.
Abstract: The binding of [3H]haloperidol to rat striatal dopamine receptors increases after lesion (made by injection of 6-hydroxydopamine) of the nigrostriatal dopamine pathway in those rats which are behaviorally supersensitive, as reflected by apomorphine-induced contralateral rotations. The enhanced binding is associated with an increased number of receptor sites with no change in their affinity.
TL;DR: When small, unilamellar lipid vesicles containing a high concentration of the fluorescent dye 6-carboxyfluorescein are incubated with either frog retinas or human lymphocytes, fluroescence distributes widely throughout each cell.
Abstract: When small, unilamellar lipid vesicles containing a high concentration of the fluorescent dye 6-carboxyfluorescein are incubated with either frog retinas or human lymphocytes, fluroescence distributes widely throughout each cell. Since "self-quenching" largely prevents the dye from fluorescing as long as it remains sequestered in vesicles, it is clear that a considerable amount of dye is released from the vesicles and diluted into the much larger volume of the cell.