Entamoeba histolytica adherence: inhibition by IgA monoclonal antibodies.
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Adenocarcinoma↗
Biomedical subjects
P Moran
Publications and source records attributed to P Moran.
Suppression of haloperidol-induced oral dyskinesias in rats by vigabatrin.
Acute and chronic administration of vigabatrin, a selective inactivator of GABA-T, suppresses haloperidol-induced dyskinesias at low doses without preventing the enhancement of striatal dopamine D2 receptor density or the development of vacuous chewing movements. The long-term administration of vigabatrin does not attenuate its effect. The observations presented in this work support the GABA hypothesis of haloperidol-induced vacuous chewing behavior in rats, and suggest that vigabatrin is an appropriate means to enhance nigral GABAergic activity.
4-Aminobutyrate Transaminase↗
Cloning of AL-1, a ligand for an Eph-related tyrosine kinase receptor involved in axon bundle formation.
REK7 is an Eph-related tyrosine kinase receptor expressed exclusively in the nervous system, predominantly in hippocampus and cortex. A soluble REK7-IgG fusion protein, produced to analyze the biological role of REK7, prevents axon bundling in cocultures of cortical neurons with astrocytes, a model of late stage nervous system development and differentiation. Using REK7-IgG as an affinity reagent, we purified and cloned a novel REK7 ligand called AL-1, a GPI-linked protein homologous to other members of an emerging ligand family. Membrane attachment of AL-1 appears necessary for receptor activation, since REK7 on cortical neurons is efficiently activated by transfected cells expressing GPI-linked AL-1, but not by soluble AL-1. Consistent with this, soluble AL-1 blocks axon bundling. Our findings, together with the observation that both molecules are expressed in the brain, suggest a role in the formation of neuronal pathways, a crucial feature of nervous system development and regeneration.
Amino Acid Sequence↗
Adolescent health-threatening and health-enhancing behaviors: a study of word association and imagery.
PURPOSE: To examine the ways in which perceived risks and benefits relate to health-threatening and health-enhancing behaviors by adolescents. METHOD: The study used a word association methodology to explore adolescents' thoughts and affective feelings associated with five health-threatening behaviors (e.g., drinking beer, smoking cigarettes) and three health-enhancing behaviors (e.g., exercising, using a seat belt). RESULTS: Each behavior elicited a mix of positive and negative associations. Health-threatening behaviors had many positive associations in common, such as having fun, social facilitation, and physiological arousal. Health-enhancing behaviors had much less commonality in their positive associations. Patterns of negative associations were not highly similar across behaviors. The content and affective tone of the associations were closely linked to participation in health-threatening behaviors and health-enhancing behaviors. Participants in an activity were far more likely than nonparticipants to associate that activity with positive outcomes, concepts, and affect and less likely to produce outcomes, concepts, and affect and less likely to produce negative associations. CONCLUSIONS: The word association methodology provides a useful technique for exploring adolescents' cognitions and affective reactions with regard to health-related behaviors. The data provided by this method have implications for prevention and intervention programs, as well as for future research.
Adolescent↗
A polymorphism in intron D of the chinook salmon growth hormone 2 gene.
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Alleles↗
Applications of 5S rDNA in Atlantic salmon, brown trout, and in Atlantic salmon x brown trout hybrid identification.
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Animals↗
Specific anti-E. histolytica IgA monoclonal antibodies.
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Animals↗
Identification and characterization of Batk, a predominantly brain-specific non-receptor protein tyrosine kinase related to Csk.
A novel cDNA, brain-associated tyrosine kinase (Batk), was isolated from a rat hippocampal library and appears to encode a new member of the Csk subfamily of non-receptor protein tyrosine kinases, with 52% overall amino acid identity to rat Csk. Batk resembles kinases of the Src family in that it contains a Src homology 2 (SH2) domain and an SH3 domain, followed by a tyrosine kinase domain. Analysis of incompletely spliced Batk cDNAs suggests that the genomic structure of Batk is similar to that of Csk with identical exon/intron boundaries. Batk also shows significant homology (86% overall amino acid identity) to the recently described human megakaryocyte-specific Matk. Although Batk is 41 amino acids shorter than Matk, Southern blot analysis suggests that Batk might be a rat homolog of Matk. Batk is predominantly expressed in the brain, with lower expression in the spleen and undetectable expression in other tissues. In situ hybridization and Northern blot analysis show that Batk is widely distributed throughout the adult brain, being primarily expressed in neurons, including those of the hippocampus and cortex. In contrast, embryos appear to have markedly decreased expression levels. Analysis of postnatal day 1 brain suggests that Batk may be upregulated at birth throughout the brain except in the cerebellum. In view of its homology to Csk, a negative regulator of Src family tyrosine kinases, and its generalized expression in the adult brain, we suggest that Batk may function as a brain-specific regulator of kinases involved in the development and maintenance of the nervous system.
Amino Acid Sequence↗
Retention and degradation of proteins containing an uncleaved glycosylphosphatidylinositol signal.
Glycosylphosphatidylinositol (GPI) membrane anchor attachment is directed by a COOH-terminal signal that is proteolytically removed and replaced with a preformed GPI anchor in a coupled reaction. Failure to complete proteolytic cleavage and anchor addition results in the retention of an uncleaved precursor in a post-endoplasmic reticulum (ER) compartment. In this report, we address three issues: (i) the exact position of the transport block, (ii) the subsequent fate of the retained molecules, i.e. where are they degraded, and (iii) the mechanism whereby these proteins are selected for retention. Using decay accelerating factor (DAF), we provide evidence that failure to cleave the GPI signal totally prevents O-glycosylation, suggesting that the uncleaved polypeptides are not transported into the cis-Golgi complex. This implies that transport is blocked at the boundary between the ER-Golgi intermediate compartment and the Golgi stacks. The degradation of an intracellularly retained human growth hormone (hGH)-DAF fusion protein containing a nonfunctional GPI signal shows some features of ER degradation, i.e. the degradation is insensitive to leupeptin, chloroquine, and ammonium chloride, and is inhibited at 16 degrees C or after ATP depletion. However, morphological evidence points to a pathway resembling autophagy. To reconcile these observations, we suggest either that hGHDAF is degraded by two distinct pathways (ER degradation and autophagy) or that ER degradation takes place in an ER-associated vesicular compartment in a process resembling autophagy. Using as probes a soluble hGH receptor and an antibody recognizing only native hGH, we show that a significant fraction of the retained protein is correctly folded, ruling out general misfolding as the basis for retention. We also show that hGHDAF fusion proteins are present in high molecular weight, disulfide-linked aggregates in COS cells. We suggest a model for retention in which the uncleaved GPI signal drives the formation of large micelle-like aggregates that cannot be secreted.
Amino Acid Sequence↗
Targeting of liposomes to cells expressing CD4 using glycosylphosphatidylinositol-anchored gp120. Influence of liposome composition on intracellular trafficking.
To test the concept that glycosylphosphatidylinositol (GPI)-anchored proteins might be useful as targeting molecules for liposomes, we engineered a GPI-anchored form of gp120 from human immunodeficiency virus type 1 (termed gp120DAF) using the GPI signal of decay-accelerating factor (DAF). We show that (i) purified gp120DAF spontaneously inserts into liposome membranes via the GPI anchor; (ii) liposomes bearing gp120DAF bind specifically to cells expressing CD4, the cellular receptor for gp120; and (iii) the receptor-bound liposomes are internalized and recycle in Chinese hamster ovary cells. To test whether the lipid composition of the liposome affects any of these processes, we compared small unilamellar liposomes containing only phosphatidylcholine and cholesterol in a 7:1 molar ratio with artificial viral envelopes that mimic the lipid composition of human immunodeficiency virus type 1. We show that when tagged with gp120DAF, both liposome preparations bind specifically to cells expressing CD4, and both are endocytosed. However, artificial viral envelope liposomes are transported to late endosomes or lysosomes in the cell interior, whereas phosphatidylcholine:cholesterol liposomes are confined to a population of vesicles that remain close to the plasma membrane. Since the binding and internalization of both liposome preparations are mediated by the same receptor, we conclude that the lipid composition of the liposome profoundly influences the subsequent intracellular trafficking of the liposome-receptor complex.
Animals↗
Requirements for glycosylphosphatidylinositol attachment are similar but not identical in mammalian cells and parasitic protozoa.
The general features of the glycosylphosphatidylinositol (GPI) signal have been conserved in evolution. To test whether the requirements for GPI attachment are indeed the same in mammalian cells and parasitic protozoa, we expressed the prototype GPI-linked protein of Trypanosoma brucei, the variant surface glycoprotein (VSG), in COS cells. Although large amounts of VSG were produced, only a small fraction became GPI linked. This impaired processing is not caused by the VSG ectodomain, since replacement of the VSG GPI signal with that of decay accelerating factor (DAF) produced GPI-linked VSG. Furthermore, whereas fusion of the DAF GPI signal to the COOH terminus of human growth hormone (hGH) produces GPI-linked hGH, an analogous hGH fusion using the VSG GPI signal does not, indicating that the VSG GPI signal functions poorly in mammalian cells. By constructing chimeric VSG-DAF GPI signals and fusing them to the COOH terminus of hGH, we show that of the two critical elements that comprise the GPI-signal--the cleavage/attachment site and the COOH terminal hydrophobic domain--the former is responsible for the impaired activity of the VSG GPI signal in COS cells. To confirm this, we show that the VSG GPI signal can be converted to a viable signal for mammalian cells by altering the amino acid configuration at the cleavage/attachment site. We also show that when fused to the COOH terminus of hGH, the putative GPI signal from the malaria circumsporozoite (CS) protein produces low levels of GPI-anchored hGH, suggesting that the CS protein is indeed GPI linked, but that the CS protein GPI signal, like the VSG-signal, functions poorly in COS cells. The finding that the requirements for GPI attachment are similar but not identical in parasitic protozoa and mammalian cells may allow for the development of selective inhibitors of GPI-anchoring that might prove useful as antiparasite therapeutics.
Amino Acid Sequence↗
Chromosomal mapping and nucleotide sequence of two tandem repeats of Atlantic salmon 5S rDNA.
Atlantic salmon 5S ribosomal DNA (5S rDNA) was amplified by the polymerase chain reaction, using as primers conserved sequences from the coding region of rainbow trout 5S rRNA. Two amplified products of different molecular weights were obtained, cloned, and sequenced, revealing them to be tandemly arranged. The nucleotide sequences differed between the two clones in the length of the nontranscribed spacer (NTS) and in three nucleotides of the coding sequence. By means of fluorescence in situ hybridization the 5S rDNA was chromosomally located in the heterochromatic arm of the pair bearing the satellite, adjacent to the major ribosomal DNA locus (rDNA).
Animals↗
Clinical and psychosocial origins of chronic depressive episodes. I: A community survey.
BACKGROUND: We consider how far it is possible to predict a chronic course of a depressive disorder from psychosocial and clinical material available at the point of onset. METHOD: A population survey found 404 working-class mothers living in an inner-city area of London. The majority were interviewed three times over a 3-year period. RESULTS: Chronicity (more than 12 months' duration) was strongly related to both childhood adversity (parental indifference, family violence or any sexual abuse) and current adult interpersonal difficulties. The lack of positive events during the course of the episode was also independently related to chronicity, but to a lesser degree. Clinical characteristics were relatively unimportant compared with psychosocial factors. CONCLUSIONS: The childhood risk factors were particularly important (judged by a path analysis), and a challenge for future research will be to establish the intervening processes involved with this distal link.
Adolescent↗
The requirements for GPI-attachment are similar but not identical in mammalian cells and parasitic protozoa.
To test whether the requirements for GPI-attachment are the same in mammalian cells and parasitic protozoa, we expressed the GPI-linked variant surface glycoprotein (VSG) of Trypanosoma brucei (T. brucei) in COS cells. Although large amounts of VSG were produced, only a small fraction became GPI-linked. This impaired processing is not due to the VSG ectodomain since replacement of the VSG GPI-signal with that of decay accelerating factor (DAF) produced GPI-linked VSG. Further, whereas fusion of the DAF GPI-signal to the COOH-terminus of human growth hormone (hGH) produces GPI-linked hGH, an analogous fusion using the VSG GPI-signal does not, indicating that the VSG GPI-signal functions poorly in mammalian cells. By constructing chimeric VSG-DAF GPI-signals and fusing them to the COOH-terminus of hGH, we show that of the two critical elements that comprise the GPI-signal--the cleavage/attachment site and the hydrophobic domain--the former is responsible for the impaired activity of the VSG GPI-signal in COS cells. To confirm this, we show that the VSG GPI-signal can be converted to a viable signal for mammalian cells by altering the amino acid configuration at the cleavage/attachment site. We also show that when fused to hGH, the putative GPI-signal from the malaria circumsporozoite (CS) protein produces low levels of GPI-anchored hGH, suggesting that the CS protein is indeed GPI-linked, but that the CS protein GPI-signal, like the VSG-signal, functions poorly in COS cells.
Amino Acid Sequence↗
Plasma concentrations of bupivacaine after wound infiltration of an 0.5% solution after inguinal herniorrhaphy: a preliminary study.
After routine inguinal herniorrhaphy we gave 12 patients a wound infiltration regimen of bolus doses of 20 ml of 0.5% bupivacaine via a catheter within the wound and rectally administered indomethacin (100 mg). Peak venous plasma bupivacaine concentrations ranged from 0.07 mg.l-1 to 1.14 mg.l-1 (mean (SD) 0.47 (0.33) mg.l-1), and occurred at between 0.25 and 2 h after the first dose. Plasma concentrations were well below the toxic threshold of 4 mg.l-1 and there was no accumulation. The regimen provided satisfactory analgesia. There were no wound infections nor signs of toxicity.
Adult↗
Human recombinant soluble decay accelerating factor inhibits complement activation in vitro and in vivo.
Complement plays a role in activating the inflammatory response and has been implicated in the pathogenesis of some inflammatory diseases. With a view toward controlling unwanted C activation, we evaluated the C regulator, human decay accelerating factor (DAF). Three forms of recombinant DAF were purified from transfected Chinese hamster ovary cells: glycophosphatidylinositol (GPI)-linked membrane DAF (mDAF) extracted from cell membranes; spontaneously shed soluble DAF (sDAF) derived from mDAF; and a novel secreted protein (seDAF), generated by deletion of the signal for GPI attachment. We show that all three molecules inhibit both the classical and alternative pathways of C activation. The following observations indicate that mDAF extracted from Chinese hamster ovary cells reincorporates into RBC membranes via its GPI anchor: 1) cells that are preincubated with mDAF and then washed remain fully protected from C-mediated hemolysis; 2) incubation with phosphatidylinositol-specific phospholipase C abolishes this protection; and 3) sDAF and seDAF, which lack a GPI anchor, do not associate with cell membranes. mDAF is a more potent inhibitor of C-mediated hemolysis than either sDAF or seDAF, suggesting that incorporation into cell membranes greatly enhances the efficiency with which DAF inhibits C activation on the cell surface. In contrast, C activation in the fluid phase is inhibited by sDAF and seDAF, but not by mDAF, possibly due to interference by serum lipoproteins. A reversed passive Arthus reaction in guinea pigs was used to evaluate the ability of recombinant seDAF to inhibit C activation in vivo. When administered at dermal sites, seDAF reduced the severity of immune complex-mediated inflammatory reactions induced by a reversed passive Arthus reaction, as judged by both gross and histologic examination. These data indicate that seDAF may be useful as an anti-inflammatory therapeutic.
Animals↗
Protection of macaques against SIV infection by subunit vaccines of SIV envelope glycoprotein gp160.
Simian immunodeficiency virus (SIV) is a primate lentivirus related to human immunodeficiency viruses and is an etiologic agent for acquired immunodeficiency syndrome (AIDS)-like diseases in macaques. To date, only inactivated whole virus vaccines have been shown to protect macaques against SIV infection. Protective immunity was elicited by recombinant subunit vaccines. Four Macaca fascicularis were immunized with recombinant vaccinia virus expressing SIVmne gp160 and were boosted with gp160 produced in baculovirus-infected cells. All four animals were protected against an intravenous challenge of the homologous virus at one to nine animal-infectious doses. These results indicate that immunization with viral envelope antigens alone is sufficient to elicit protective immunity against a primate immunodeficiency virus. The combination immunization regimen, similar to one now being evaluated in humans as candidate human immunodeficiency virus (HIV)-1 vaccines, appears to be an effective way to elicit such immune responses.
Animals↗
A study of heat production and heat loss in crated broiler chickens: a mathematical model for a single bird.
1. A steady state model of heat production and loss in crated broiler chickens is presented. 2. The model is based on physiological factors and uses experimental data from various sources. 3. Although many of the required parameters are not well defined at present, the model allows a better understanding of the processes which lead to hyperthermic stress in crated broiler chickens, and is relevant to the design of ventilation systems for poultry transporters.
Animals↗