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Showing papers by "University of California, San Francisco published in 1983"


Journal ArticleDOI
16 Sep 1983-Science
TL;DR: Emotion-specific activity in the autonomic nervous system was generated by constructing facial prototypes of emotion muscle by muscle and by reliving past emotional experiences, and distinguished not only between positive and negative emotions, but also among negative emotions.
Abstract: Emotion-specific activity in the autonomic nervous system was generated by constructing facial prototypes of emotion muscle by muscle and by reliving past emotional experiences. The autonomic activity produced distinguished not only between positive and negative emotions, but also among negative emotions. This finding challenges emotion theories that have proposed autonomic activity to be undifferentiated or that have failed to address the implications of autonomic differentiation in emotion.

2,145 citations


Journal ArticleDOI
01 Dec 1983-Nature
TL;DR: It is shown here that a DNA domain detectable by partial homology to the myc oncogene is amplified up to 140-fold in cell lines derived from different human neuroblastomas and in a neuroblastoma tumour, but not in other tumour cells showing cytological evidence for gene amplification.
Abstract: Amplified cellular genes in mammalian cells frequently manifest themselves as double minute chromosomes (DMs) and homogeneously staining regions of chromosomes (HSRs). With few exceptions both karyotypic abnormalities appear to be confined to tumour cells. All vertebrates possess a set of cellular genes homologous to the transforming genes of RNA tumour viruses, and there is circumstantial evidence that these cellular oncogenes are involved in tumorigenesis. We have recently shown that DMs and HSRs in cells of the mouse adrenocortical tumour Y1 and an HSR in the human colon carcinoma COLO320 contain amplified copies of the cellular oncogenes c-Ki-ras and c-myc, respectively. Both DMs and HSRs are found with remarkable frequency in cells of human neuroblastomas. We show here that a DNA domain detectable by partial homology to the myc oncogene is amplified up to 140-fold in cell lines derived from different human neuroblastomas and in a neuroblastoma tumour, but not in other tumour cells showing cytological evidence for gene amplification. By in situ hybridization we found that HSRs are the chromosomal sites of the amplified DNA. The frequency with which this amplification appears in cells from neuroblastomas and its apparent specificity raise the possibility that one or more of the genes contained within the amplified domain contribute to tumorigenesis.

1,366 citations


Journal ArticleDOI
TL;DR: Results indicate that the CSI is a brief, easily administered instrument which identified strain within the authors' sample of informal care providers, and might be usefully included in any interview or assessment package that examines intergenerational relations involving dependency and care.
Abstract: This paper outlines the development of a Caregiver Strain Index (CSI) with a sample of spouses, family, friends, and neighbors, aged 22 to 83, who provided varying degrees of care to recently hospitalized hip surgery and heart patients aged 65 and over. Internal consistency (Cronbach's alpha) for the 13-item CSI on 81 cases was .86. Evidence of construct validity was obtained in three areas: ex-patient characteristics; subjective perceptions of the care-taking relationship by caregivers; and emotional health of caregivers. These results indicate that the CSI is a brief, easily administered instrument which identified strain within our sample of informal care providers. Further development of the CSI is being undertaken for predicting specific caregiver populations at risk. This simple index might be usefully included in any interview or assessment package that examines intergenerational relations involving dependency and care.

1,339 citations


Journal ArticleDOI
TL;DR: It is concluded that patient satisfaction information can provide a dependent measure of service quality and serves as a predictor of health-related behavior.

1,214 citations


Journal ArticleDOI
01 Dec 1983-Cell
TL;DR: The findings raise the possibility that the amyloid plaques observed in transmissible, degenerative neurological diseases might consist of prions, a polymeric form of the scrapie prion.

1,051 citations


Journal ArticleDOI
TL;DR: This paper found that after the median nerve was transected and ligated in adult owl and squirrel monkeys, the cortical sectors representing it within skin surface representations in Areas 3b and 1 were completely occupied by 'new' and expanded representations of surrounding skin fields.

948 citations


Journal ArticleDOI
01 Nov 1983-Cell
TL;DR: Fractions purified from scrapie-infected hamster brain contain a unique protein, designated PrP, which is found to be directly proportional to the titer of the infectious prion.

926 citations



Journal ArticleDOI
TL;DR: The results of studies directed toward determining the time course and likely mechanisms underlying this remarkable plasticity of the cortex representing the skin of the median nerve within parietal somatosensory fields 3b and 1 are described.

725 citations


Journal ArticleDOI
TL;DR: It is shown that the homogeneously staining regions of the COLO 320 HSR marker chromosome contain amplified c- myc, and it seems reasonable to suspect that amplification of c-myc may have contributed to tumorigenesis.
Abstract: Two human neuroendocrine tumor cell lines derived from a colon carcinoma contain either numerous double minute chromosomes (COLO 320 DM) or a homogeneously staining marker chromosome (COLO 320 HSR). We found amplification and enhanced expression of the cellular oncogene c-myc in both COLO 320 DM and HSR cells, and we were able to show that the homogeneously staining regions of the COLO 320 HSR marker chromosome contain amplified c-myc. From previous and present karyotypes, it appears that the homogeneously staining regions reside on a distorted X chromosome. Therefore, amplification of c-myc has been accompanied by translocation of the gene from its normal position on chromosome 8 (8q24). Because double minute chromosomes were features of primary cultures from the original tumor, it seems reasonable to suspect that amplification of c-myc may have contributed to tumorigenesis.

698 citations


Journal ArticleDOI
23 Sep 1983-Science
TL;DR: The control of angiogenesis in wound healing may be the result of macrophages responding to tissue oxygen tension without the necessity of interacting with other cell types or biochemical signals.
Abstract: When cultured in a hypoxic environment similar to that found in the center of a wound, macrophages secreted active angiogenesis factor into the medium. Under conditions similar to those of well-oxygenated tissue, macrophages did not secrete active angiogenesis factor. Macrophages that secreted the factor at hypoxic conditions stopped secreting it when returned to room air. Thus the control of angiogenesis in wound healing may be the result of macrophages responding to tissue oxygen tension without the necessity of interacting with other cell types or biochemical signals.

Journal ArticleDOI
01 Jun 1983-Cell
TL;DR: It is concluded that the MTV promoter region contains a "glucocorticoid response element" that can be separated from a second element essential for MTV transcription initiation, implying that receptor binding at these sites in vivo may mediate hormone responsiveness.

Journal ArticleDOI
01 Dec 1983-Cell
TL;DR: Five regions of MTV DNA that are bound specifically by purified receptor are mapped and compared, suggesting that receptor affinity for upstream and internal regions may differ by less than one order of magnitude.

Journal ArticleDOI
01 Dec 1983-Nature
TL;DR: DNA sequences containing the 5′-flanking regions of the insulin and chymotrypsin genes were linked to the coding sequence of the chloramphenicol acetyltransferase (CAT) gene, which elicits preferential expression of CAT activity when introduced into cells producing insulin.
Abstract: DNA sequences containing the 5′-flanking regions of the insulin and chymotrypsin genes were linked to the coding sequence of the chloramphenicol acetyltransferase (CAT) gene. The insulin gene recombinant elicits preferential expression of CAT activity when introduced into cells producing insulin; similarly, the chymotrypsin gene recombinant elicits preferential expression in chymotrypsin-producing cells. Sequences located upstream of previously defined transcriptional control elements are essential for efficient expression in both cases.

Journal ArticleDOI
17 Nov 1983-Nature
TL;DR: It is reported here that the arrangement of electrostatic charges in SOD promotes productive enzyme–substrate interaction through substrate guidance and charge complementarity: sequence-conserved residues create an extensive electrostatic field that directs the negatively charged superoxide substrate to the highly positive catalytic binding site at the bottom of the active-site channel.
Abstract: Electrostatic forces have been implicated in a variety of biologically important molecular interactions including drug orientation by DNA, protein folding and assembly, substrate binding and catalysis and macromolecular complementarity with inhibitors, drugs and hormones. To examine enzyme-substrate interactions in copper, zinc superoxide dismutase (SOD), we developed a method for the visualization and analysis of an enzyme's three-dimensional electrostatic vector field that allows the contributions of specific residues to be identified. We report here that the arrangement of electrostatic charges in SOD promotes productive enzyme-substrate interaction through substrate guidance and charge complementarity: sequence-conserved residues create an extensive electrostatic field that directs the negatively charged superoxide (O-2) substrate to the highly positive catalytic binding site at the bottom of the active-site channel. Dissection of the electrostatic potential gradient indicated the relative contributions of individual charged residues: Lys 134 and Glu 131 seem to have important roles in directing the long-range approach of O-2, while Arg 141 has local orienting effects. The reported methods of analysis may have general application for the elucidation of intermolecular recognition processes.

Journal ArticleDOI
TL;DR: It is proposed that off- cells must pause if the tail flick is to occur, and that this pausing allows the transmission of nociceptive input through spinal reflex loops.
Abstract: Neurons of the rostral ventromedial medulla (RVM) have been implicated in the modulation of nociceptive transmission. In order to further analyze their role in pain behavior, we studied their activity while eliciting the tail flick reflex with noxious heat. Recording sites were regions in the RVM from which microstimulation (less than or equal to 10 microA, 400 mu sec, 50 Hz continuous pulse trains) inhibited the tail flick reflex. Extracellular unit activity and tail temperature were recorded, stored, and plotted with reference to either the time of tail flick or the time when the stimulating temperature reached 45 degrees C. Neuronal discharges were found to be either increased (on-cells), decreased (off-cells), or unchanged around the time of the tail flick. The decreases in discharge were more closely correlated with the tail flick behavior than with the temperature of the stimulus. These off-cells were located at sites of lowest threshold for tail flick inhibition and tended to be ventral to on-cells. We propose that off-cells must pause if the tail flick is to occur, and that this pausing allows the transmission of nociceptive input through spinal reflex loops.

Journal ArticleDOI
07 Apr 1983-Nature
TL;DR: The nucleotide sequence of a submaxillary cDNA encoding the mouse NGF precursor (preproNGF) is reported, in contrast to previous suppositions, where the NGF moiety is situated near the carboxy-terminus of the polyprotein precursor.
Abstract: Nerve growth factor (NGF) is a polypeptide that enhances survival, nerve fibre outgrowth and neurotransmitter biosynthesis in sympathetic and sensory neurones. Administration of antibodies against NGF to developing animals leads to atrophy of the sympathetic system. NGF is not normally detectable in innervated tissues but ablation of the innervating neurones leads to the production of measurable NGF in the target tissue. After transplantation of the denervated tissue, reinnervation occurs, then NGF decreases to undetectable levels. Thus NGF seems to act as a neurotrophic messenger and its level is regulated by innervating neurones. Because of the minute levels present it is very difficult to study NGF biosynthesis in innervated tissue. However, NGF can be isolated from male mouse submaxillary glands, where it exists in inexplicably high levels. Its amino acid sequence has been determined, and the synthesis of NGF and its larger precursors has been demonstrated in cultured submaxillary glands. We report here the nucleotide sequence of a submaxillary cDNA encoding the mouse NGF precursor (preproNGF). In contrast to previous suppositions the NGF moiety is situated near the carboxyterminus of the polyprotein precursor. It is flanked at the amino-terminus by 187 amino acids which may be cleaved at dibasic residues to generate three peptides; there are only two additional amino acids at the carboxy-terminus.

Book ChapterDOI
TL;DR: Urogenital mesenchyme induces specific epithelial morphogenesis, growth, and function within the genital tract and that the hormonal sensitivity of these morphogenetic processes resides in the mesenchYme that invariably contains nuclear hormone receptors.
Abstract: Publisher Summary This chapter explains the role of mesenchymal–epithelial interactions in hormone induced morphogenesis and growth. The mechanism of steroid hormone action is thought to involve specific high-affinity receptor proteins. The hormone enters the cell, binds to the cytoplasmic receptor, which after activation translocates to the nucleus. The hormone–receptor complex in turn binds to nuclear acceptor sites on the chromatin. This activates a variety of metabolic processes, the most important being the stimulation of messenger RNA (mRNA) synthesis and the ultimate production of new proteins. The first indication that androgens can elicit their effects upon epithelial morphogenesis via the mediation of mesenchymal cells comes from studies in which urogenital epithelia from the embryonic seminal vesicle or urogenital sinus are grown in association with either urogenital mesenchyme or with non-target integumental mesenchyme. Urogenital mesenchyme induces specific epithelial morphogenesis, growth, and function within the genital tract and that the hormonal sensitivity of these morphogenetic processes resides in the mesenchyme that invariably contains nuclear hormone receptors. As morphogenetic processes are cyclic in adult genital tracts of many species, developmental properties are expressed in adulthood and, for this reason, appear to play a regulatory role in abnormal epithelial differentiation including carcinogenesis.

Journal ArticleDOI
01 Dec 1983-Nature
TL;DR: The cellular oncogene c-Ki-ras is amplified 30- to 60-fold in cells of the mouse adrenocortical tumour Y1, contributing to the genesis and/or maintenance of at least some naturally occurring tumours.
Abstract: The cellular oncogene c-Ki-ras is amplified 30- to 60-fold in cells of the mouse adrenocortical tumour Y1 The amplified oncogene is located in double minute chromosomes and in a homogeneously staining chromosomal region, common karyotypical anomalies of tumour cells The amounts of c-Ki-ras specific mRNA and of the protein (p21) encoded by the amplified gene are correspondingly elevated Amplification and enhanced expression of cellular oncogenes may contribute to the genesis and/or maintenance of at least some naturally occurring tumours


Journal ArticleDOI
21 Apr 1983-Nature
TL;DR: The three-dimensional chromosome topography in an intact nucleus has been determined using fluorescently stained Drosophila polytene chromosomes, optical fluorescence microscopy and newly developed, generally applicable, cellular image reconstruction techniques.
Abstract: The three-dimensional chromosome topography in an intact nucleus has been determined using fluorescently stained Drosophila polytene chromosomes, optical fluorescence microscopy and newly developed, generally applicable, cellular image reconstruction techniques. The folding pattern is a complex mixture of parallel chromosomal segments and intertwined coils and shows extensive interaction of the chromosomes with the nuclear envelope.

Journal ArticleDOI
15 Jul 1983-Science
TL;DR: The structure of the messenger RNA encoding the precursor to mouse submaxillary epidermal growth factor (EGF) was determined from the sequence of a set of overlapping complementary DNA's (cDNA).
Abstract: The structure of the messenger RNA (mRNA) encoding the precursor to mouse submaxillary epidermal growth factor (EGF) was determined from the sequence of a set of overlapping complementary DNA's (cDNA). The mRNA is unexpectedly large, about 4750 nucleotide bases, and predicts the sequence of preproEGF, a protein of 1217 amino acids (133,000 molecular weight). The EGF moiety (53 amino acids) is flanked by polypeptide segments of 976 and 188 amino acids at its amino and carboyxl termini, respectively. The amino terminal segment of the precursor contains seven peptides with sequences that are similar but not identical to EGF.

Journal ArticleDOI
21 Jan 1983-Science
TL;DR: Highly purified preparations of insulin receptor catalyzed the phosphorylation of the 95,000-dalton subunit of the insulin receptor, suggesting that the insulin receptors is itself a protein kinase.
Abstract: Highly purified preparations of insulin receptor catalyzed the phosphorylation of the 95,000-dalton subunit of the insulin receptor. This subunit of the insulin receptor was also labeled with [alpha-32P]8-azidoadenosine 5'-triphosphate, a photoaffinity label for adenosine triphosphate binding sites. The identity of the 95,000-dalton band was confirmed in both cases by precipitation with a monoclonal antibody to the insulin receptor. These results suggest that the insulin receptor is itself a protein kinase.

Journal ArticleDOI
01 Apr 1983-Cell
TL;DR: It is concluded that negatively charged liposomes are endocytosed and processed intracellularly by the coated vesicles pathway, and acidification of the endocytic vesicle, rather than liposome fusion, permits escape of certain molecules to the cytoplasm.

Journal ArticleDOI
01 May 1983-Cell
TL;DR: This report reviews pertinent literature and formulates a proposal for the molecular mechanism by which DCMT is inhibited by DNA containing 5-aza-C or 5fluoroC.

Journal ArticleDOI
TL;DR: The basic theorems of distance geometry in Euclidean space are presented and formal proofs of the correctness and, where possible, of the complexity of these algorithms are given.

Journal ArticleDOI
23 Sep 1983-Science
TL;DR: These findings provide electrophysiological support for the role of acetylcholine as a synaptic transmitter in the brain and demonstrate that nonclassical synaptic responses involving the blockade of membrane conductances exist in thebrain.
Abstract: The hippocampal slice preparation was used to study the role of acetylcholine as a synaptic transmitter. Bath-applied acetylcholine had three actions on pyramidal cells: (i) depolarization associated with increased input resistance, (ii) blockade of calcium-activated potassium responses, and (iii) blockade of accommodation of cell discharge. All these actions were reversed by the muscarinic antagonist atropine. Stimulation of sites in the slice known to contain cholinergic fibers mimicked all the actions. Furthermore, these evoked synaptic responses were enhanced by the cholinesterase inhibitor eserine and were blocked by atropine. These findings provide electrophysiological support for the role of acetylcholine as a synaptic transmitter in the brain and demonstrate that nonclassical synaptic responses involving the blockade of membrane conductances exist in the brain.

Journal ArticleDOI
TL;DR: Measurements from stimulation of a single channel at a time of cochlear implants indicate a central mechanism that is still intact in implant patients, and the shape of the threshold vs. frequency curve can be partially related to the membrane biophysics of the remaining spiral ganglion and/or dendrites.

Journal ArticleDOI
TL;DR: GH, prolactin, and chorionic somatomammotropin are a family of polypeptide hormones related by function, immunochemistry, and structure but despite their relatedness, these hormones are synthesized in a tissue-specific manner.
Abstract: Introduction GROWTH HORMONE (GH), prolactin (Prl), and chorionic somatomammotropin (CS, placental lactogen) are a family of polypeptide hormones that are related by function, immunochemistry, and structure (1–5). Despite their relatedness, these hormones are synthesized in a tissue-specific manner. GH and Prl are produced in the anterior pituitary, whereas CS is produced by the syncytiotrophoblast of the placenta. All three hormones possess lactogenic and growth-promoting activities. GH is required for postnatal growth and maintenance of nitrogen, mineral, lipid, and carbohydrate metabolism (6), while mammalian Prl is primarily involved in the initiation and maintenance of lactation (7). CS may provide GH-like activities to the developing fetus (8, 9), although it does not appear to be an essential hormone (10). The three hormones have a similar size (190 to 199 amino acids among various species) and they all have similar protein structures. Each hormone has a single homologous tryptophan residue at about...

Journal ArticleDOI
01 May 1983-Blood
TL;DR: Application of this approach to a variety of pathologic blood samples showed that various hematologic disorders can be characterized by the shape of this profile and the position of specific features of the profile along the osmolality axis.