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A Barton

Publications and source records attributed to A Barton.

At least 55 records · Page 3Linked to original sources

The YAL017 gene on the left arm of chromosome I of Saccharomyces cerevisiae encodes a putative serine/threonine protein kinase.

The DNA sequence of a region between the LTE1 and CYS3 genes on the left arm of chromosome I from Saccharomyces cerevisiae contains an open reading frame (ORF), YAL017, corresponding to the 5.0 kb FUN31 (Function Unknown Now) transcribed region. The predicted protein from this ORF contains 1358 amino acid residues with a molecular weight of 152,531, and an identifiable serine/threonine protein kinase catalytic domain. When compared with other yeast protein kinases, the Yal017p kinase most resembles the SNF1 serine/threonine protein kinase which is involved in regulating sucrose fermentation genes. The Yal017p kinase shows highest amino acid identities with two mammalian carcinoma-related serine/threonine protein kinases; PIM-1, which shows induced expression in T-cell lymphomas; and p78A1, whose expression is lost in human pancreatic carcinomas. Gene disruption of YAL017 indicates that it is non-essential for growth on glucose.

Amino Acid Sequence↗

First use of G-CSF in chlorpromazine-induced agranulocytosis: a report of two cases.

Chlorpromazine-induced agranulocytosis is an uncommon disorder associated with a high frequency of fatality. We describe two patients with chlorpromazine-induced granulocytosis in whom granulocyte colony stimulating factor (G-CSF) administration enhanced the speed of neutrophil recovery. No toxicity was noted with G-CSF and both patients made a successful recovery. We propose there is a role for such cytokine therapy in patients with life-threatening agranulocytosis in order to speed the recovery of neutrophils.

Adult↗

Sequencing of chromosome I from Saccharomyces cerevisiae: analysis of a 32 kb region between the LTE1 and SPO7 genes.

The DNA sequencing and preliminary functional analysis of a 32 kb section of yeast chromosome I has been completed. This region lies on the left arm of the chromosome between the LTE1 and SPO7 genes and contains 14 open reading frames (ORFs) positioned closely together, with an average spacing of approximately 350 nucleotides between coding regions. Three of these ORFs correspond to previously identified genes, a further three show significant homology with other proteins, while the remaining eight ORFs share no significant homology to genes in the databases.

Amino Acid Sequence↗

Identification of a Saccharomyces cerevisiae homolog of the SNF2 transcriptional regulator in the DNA sequence of an 8.6 kb region in the LTE1-CYS1 interval on the left arm of chromosome I.

The DNA sequence of an 8.6 kb region of the left arm of chromosome I has been determined. This region, between the LTE1 and CYS1 loci, is approximately 40 kb from the centromere. There are six potential open-reading frames (ORFs), provisionally named YAL001-006 within this fragment of chromosome I. Four of these ORFs can be aligned with previously identified FUN transcripts: FUN28 with YAL006, FUN29 with YAL004, FUN30 with YAL001 and FUN31 with YAL002. The YAL001 ORF shows significant homology to the SNF2 transcriptional regulator. A region of the DNA contains an extensive repeat of the bases C-A-T positioned in the 5' terminus of the YAL004 promoter region.

Adenosine Triphosphatases↗

Molecular cloning of the rat integrin alpha 1-subunit: a receptor for laminin and collagen.

Integrin heterodimers mediate a variety of adhesive interactions, including neuronal attachment to and process outgrowth on laminin. We report here the cloning and primary sequence of an M-200 kD integrin alpha subunit that associates with the integrin beta 1 subunit to form a receptor for both laminin and collagen. Similarities in ligand-binding specificity, relative molecular mass and NH2-terminal sequence make this a strong candidate for the rat homologue of the alpha subunit of the human integrin VLA-1. The full-length rat alpha 1 cDNAs encode a protein containing a purative signal sequence and a mature polypeptide of 1,152 amino acids, with extracellular, transmembrane and cytoplasmic domains. Several structural features are conserved with other integrin alpha chains, including (a) a sequence motif repeated seven times in the NH2-terminal half; (b) potential Ca2+/Mg2+ binding sites in repeats 5, 6, and 7, and (c) alignment of at least 14 of 23 cysteine residues. This rat alpha 1 sequence also contains a 206-amino acid I domain, inserted between repeats 2 and 3, that is homologous to I domains found in the same position in the alpha subunits of several integrins (VLA-2, Mac-1, LFA-1, p150). The rat alpha 1 and human VLA-2 apha subunits share greater than 50% sequence identity in the seven repeats and I domain, suggesting that these sequence identities may underlie some of their similar ligand-binding specificities. However, the rat integrin alpha 1 subunit has several unique features, including a 38-residue insert between two Ca2+/Mg2+ binding domains, and a divergent 15-residue cytoplasmic sequence, that may potentially account for unique functions of this integrin.

Adrenal Gland Neoplasms↗

Low plasma iron status and akathisia.

Thirty patients were examined to test the hypothesis that a depletion of iron levels is associated with symptoms of akathisia. Fifteen akathisic patients were pair-matched with 15 non-akathisic patients. Plasma ferritin levels were significantly decreased in the akathisic patients, and there was a significant inverse correlation between plasma iron levels and akathisia rating. In addition, akathisia ratings were found to be correlated with a scale measuring symptoms of tardive dyskinesia.

Adult↗

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Autopsy↗

Antibacterial properties of eosinophil major basic protein and eosinophil cationic protein.

We examined the bactericidal activity of two proteins that are abundant in the cytoplasmic granules of human eosinophils, major basic protein (MBP) and eosinophil cationic protein (ECP). Unlike the human neutrophil's peptide defensins, both MBP and ECP killed stationary phase Staphylococcus aureus 502A in a simple nutrient-free buffer solution. Although MBP also killed Escherichia coli ML-35 with considerable efficacy under these experimental conditions, the in vitro activity of ECP against E. coli was considerably enhanced if mid-logarithmic phase bacteria replaced stationary phase organisms or if the assay medium was enriched with trypticase soy broth. The antibacterial activity of both eosinophil proteins was modulated by incubation time, protein concentration, temperature and pH. A pBR322-transformed derivative of E. coli ML-35 was used to examine the effects of ECP and MBP on integrity of the bacterial inner membrane (IM) and outer membrane. Although both MBP and ECP caused outer and inner membrane permeabilization when nutrients were present, only MBP was effective under nutrient-free conditions. Two proton ionophores (DNP and carbonyl cyanide m-chlorophenyl hydrazone) protected E. coli from the bactericidal effects of ECP but not from MBP. These findings establish that MBP and ECP have bactericidal properties and suggest that these proteins kill E. coli by similar but nonidentical mechanisms marked by an attack on the target cell's membranes. In view of evidence that high concentrations of ECP and MBP exist in cytoplasmic granules whose contents are translocated to phagocytic vacuoles, we suggest that MBP and ECP contribute to the eosinophil's ability to kill ingested bacteria.

Blood Bactericidal Activity↗

Interaction of human defensins with Escherichia coli. Mechanism of bactericidal activity.

Defensins are small, cysteine-rich antimicrobial peptides that are abundant in human, rabbit, and guinea pig neutrophils (PMN). Three defensins (human neutrophil peptide defensin [HNP]-1, HNP-2, and HNP-3) constitute between 30 and 50% of the total protein in azurophil granules of human PMN. We examined the mechanism of HNP-mediated bactericidal activity against Escherichia coli ML-35 (i-, y-, z+) and its pBR322-transformed derivative, E. coli ML-35p. Under conditions that supported bactericidal activity, HNP-1 sequentially permeabilized the outer membrane (OM) and inner membrane (IM) of E. coli. Coincident with these events, bacterial synthesis of DNA, RNA, and protein ceased and the colony count fell. Although these events were closely coupled under standard assay conditions, OM permeabilization was partially dissociated from IM permeabilization when experiments were performed with E. coli that had been plasmolyzed by mannitol. Under such conditions, the rate and extent of bacterial death more closely paralled loss of IM integrity than OM permeabilization. Electron microscopy of E. coli that had been killed by defensins revealed the presence of striking electron-dense deposits in the periplasmic space and affixed to the OM. Overall, these studies show that HNP-mediated bactericidal activity against E. coli ML-35 is associated with sequential permeabilization of the OM and IM, and that inner membrane permeabilization appears to be the lethal event.

Blood Bactericidal Activity↗

Concurrent assessment of inner and outer membrane permeabilization and bacteriolysis in E. coli by multiple-wavelength spectrophotometry.

We developed a dual wavelength spectrophotometric assay that permitted beta-lactamase and beta-galactosidase activities to be measured concurrently in a single sample. We also constructed a target cell, E. coli ML-35p, that was substantially cryptic for its periplasmic beta-lactamase and cytoplasmic beta-galactosidase unless outer membrane (beta-lactamase) or inner membrane (beta-galactosidase) permeabilization occurred. By applying the spectrophotometric assay to whole target cells, we could ascertain the kinetics of inner and outer membrane permeabilization by biological agents, including serum, polymyxin B and mellitin. By monitoring the reactions at an additional wavelength, we could also follow the kinetics of serum-mediated bacteriolysis. These experiments illustrate the principle of multiple wavelength spectrophotometry and provide examples of its use to monitor and dissect the action of biological agents on a gram-negative bacterium.

Bacteriolysis↗

Human emotion communication by touch: a modified replication of an experiment by Manfred Clynes.

In 1973 Manfred Clynes wrote a paper about the biocybernetics of emotion communication in which he described an experiment which seemed to point to a universal metalanguage with which human beings communicate specific emotions by touch. In an attempt to confirm Clyne's findings by replicating his experiment, a flaw was discovered in the design of his apparatus for detecting tactile patterns, and the replication study was undertaken using an improved pressure-detection instrument. Data from the replication study were analysed using various techniques but no correlations were found to confirm Clyne's original work.

Adult↗

A disorder of cortical GABAergic innervation in Alzheimer's disease.

Synaptosomal gamma-aminobutyric acid (GABA) uptake has been used as a biochemical marker for GABAergic terminals in controls and Alzheimer disease brains. Use of this marker suggests a large (ca. 70%) loss of cortical and hippocampal GABA terminals in Alzheimer brain. To explain this observation we suggest that neuron loss in this disorder occurs via a process of cortical retrograde degeneration. This scheme reconciles our findings with previous neurochemical measurements on Alzheimer disease brains and also better reconciles the biochemistry with the histology of the disorder.

Aged↗

Region-specific loss of glutamate innervation in Alzheimer's disease.

Synaptosomal D-aspartate has been used as a marker for glutamate neurons in control and in postmortem Alzheimer's disease brains. This technique shows a marked (60%) decrease of the glutamate uptake site in cortical and hippocampal regions. There were no significant changes in subcortical regions. We interpret these results as indicating loss of, or damage to, cortical glutamatergic innervation. These losses probably represent the biochemical correlate of pyramidal neuron damage in Alzheimer's disease.

Alzheimer Disease↗

Cyclic neutropenia as a premalignant manifestation of acute lymphoblastic leukemia.

A 20-year-old female from the Philippines developed anemia and granulocytopenia. With androgen therapy, her anemia improved but she continued to show a pattern of fluctuating neutropenia consistent with human cyclic neutropenia: Blood neutrophil oscillation was regular with a periodicity of 21 days. She developed recurrent pharyngitis and apthous stomatitis but there was no cycling of other blood elements. Bone marrow aspiration and biopsy showed normal developing myeloid cells, a clonal chromosomal abnormality, and myelofibrosis. During the fourth documented cycle, blasts appeared and complete lymphoblastic transformation ensued. Blast cells were CALLA positive, Ia positive, and contained intranuclear TdT; they were negative for E, EAC, and EA rosettes. She was treated for non-T, non-B CALLA-positive ALL and within 6 weeks was in a remission without evidence of cycling neutrophil counts. This young woman's case suggests that cyclic neutropenia may represent a previously unrecognized premalignant state associated with acute lymphoblastic leukemia.

Adult↗