Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In electron micrographs of conventionally prepared thin sections of Escherichia coli one observes (i) a wavy appearance of the two membranes showing frequent appositions (named adhesion sites) and (ii) intermembrane bridges after plasmolysis which, it is claimed, occur at the adhesion sites and are related to intermembrane protein transport (transmigration). When chemical fixation is replaced by cryofixation, the observations are very different. (a) The two membranes are equally spaced and no contacts, adhesions or other sorts of connections are visible. (b) After plasmolysis the protoplast is shrunken, but the typical bridges are no longer produced. (c) In addition, when peptidoglycan is stained on conventionally prepared sections, it is revealed as a 7-nm-thick sacculus which is not interrupted at the sites of apposition. In view of the new observations, the structural concepts derived from conventionally prepared material must be revised. It is proposed that the intermembrane space is entirely filled by a gel, the outer part of which is the 7 nm thick, very stable, chemically resistant peptidoglycan (or murein). The inner part is much less stable and is proposed to undergo rapid autolytic changes upon cell death. The large 'Bayer bridges' might then tentatively be explained as an artificial post-mortem enhancement of either a stream of proteins transmigrating across the periplasm or of a pre-existing, but not yet resolved, structure. This enhancement probably occurs during the 7-10 min between plasmolysis and fixation that are prescribed for the procedure necessary for revealing 'Bayer bridges'.
Mol Microbiol 1990 May
PMID:The 'Bayer bridges' confronted with results from improved electron microscopy methods. 220 66

During hyperosmotic shock, the protoplast and stretched-out peptidoglycan layer first shrink together until the turgor pressure in the cell is relieved. Being non-compressible, the outer and inner membranes must fold their superfluous surfaces. While the protoplast contracts further, the inner membrane rearranges into plasmolysis spaces visible by phase-contrast microscopy. Two opposing theories predict a similar positioning of spaces in dividing cells and filaments: the 'periseptal annulus model', based on adhesion zones, involved in the predetermination of the division site; and a 'restricted, random model', based on physical properties of the protoplast. Strong osmotic shock causes retraction of the inner membrane over almost the entire surface forming the so-called 'Bayer bridges'. These tubular adhesion sites are preserved by chemical fixation, and can be destroyed by cryofixation and freeze-substitution of unfixed cells. Both the regular positioning of the plasmolysis spaces and the occurrence of tubular adhesion sites can be explained on the basis of physical properties of the membrane which necessitate rearrangements by membrane flow during shrinkage of the protoplast.
Mol Microbiol 1994 Nov
PMID:Significance of plasmolysis spaces as markers for periseptal annuli and adhesion sites. 855 78

We have established an expression system for full-length HIV-1 transactivator (Tat) protein in Escherichia coli. By constructing a synthetic gene for high level expression in enteric bacteria, the recombinant protein can be obtained in high yield. Fusion of the Tat sequence to an N-terminal histidine tag allows the rapid purification of the fusion protein through a single chromatographic step. After cleavage of the fusion protein with CNBr, pure Tat can be obtained through the use of a MonoS column. Reduction of the protein with Tris(2-carboxyethyl)phosphine-HCl and subsequent stepwise refolding yields biologically active Tat. Sample purity and the identity of the protein mass with the mass expected from the amino acid sequence was demonstrated by mass spectrometry. Nuclear magnetic resonance spectroscopy showed the identity of bacterially expressed and chemically synthesized Tat protein (P. Bayer et al., 1995, J. Mol. Biol. 247, 529-535). The expression of Tat in E. coli enables isotope labeling as a prerequisite for multidimensional NMR experiments toward the elucidation of the structure of the Tat-trans-activation response element complex.
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PMID:Cloning, high-yield expression in Escherichia coli, and purification of biologically active HIV-1 Tat protein. 881 37

The Bayer-Technicon hematological devices differentiate leukocytes by their peroxidase activity and their volume, displaying them as separate clusters. Peroxidase deficiencies are manifested by the irregular location of these clusters. This makes it possible to identify persons totally or partially lacking myeloperoxidase. The deficiency is quantified by the myeloperoxidase index, which is expressed for every routine analysis and for which normal values were determined. Values of the myeloperoxidase index confirm varying degrees of deficiency and prevalence. Family studies using these degrees show that the hereditary pattern must be more complicated than the classical autosomal-recessive mode. A bigenic mode is suggested. While about half of the totally deficient individuals detected were free of typical symptoms, in the other half we found infectious complications that were sometimes life-threatening. The hematological devices allow the identification of persons suffering from eosinoperoxidase deficiency and from MPO deficiency of the monocytes. The latter symptom seems to indicate immaturity of these cells and may lead to unexpected diagnosis of malignancy.
J Mol Med (Berl) 1998 Sep
PMID:Prevalence of myeloperoxidase deficiency: population studies using Bayer-Technicon automated hematology. 976 44

The second generation Hoechst-Bayer non-nucleoside inhibitor, HBY 097 (S-4-isopropoxycarbonyl-6-methoxy-3-(methylthiomethyl)-3, 4-dihydroqui noxalin-2(1H)-thione), is an extremely potent inhibitor of HIV-1 reverse transcriptase (RT) and of HIV-1 infection in cell culture. HBY 097 selects for unusual drug-resistance mutations in HIV-1 RT (e.g. Gly190Glu) when compared with other non-nucleoside RT inhibitors (NNRTIs), such as nevirapine, alpha-APA and TIBO. We have determined the structure of HBY 097 complexed with wild-type HIV-1 RT at 3.1 A resolution. The HIV-1 RT/HBY 097 structure reveals an overall inhibitor geometry and binding mode differing significantly from RT/NNRTI structures reported earlier, in that HBY 097 does not adopt the usual butterfly-like shape. We have determined the structure of the Tyr188Leu HIV-1 RT drug-resistant mutant in complex with HBY 097 at 3.3 A resolution. HBY 097 binds to the mutant RT in a manner similar to that seen in the wild-type RT/HBY 097 complex, although there are some repositioning and conformational alterations of the inhibitor. Conformational changes of the structural elements forming the inhibitor-binding pocket, including the orientation of some side-chains, are observed. Reduction in the size of the 188 side-chain and repositioning of the Phe227 side-chain increases the volume of the binding cavity in the Tyr188Leu HIV-1 RT/HBY 097 complex. Loss of important protein-inhibitor interactions may account for the reduced potency of HBY 097 against the Tyr188Leu HIV-1 RT mutant. The loss of binding energy may be partially offset by additional contacts resulting from conformational changes of the inhibitor and nearby amino acid residues. This would suggest that inhibitor flexibility can help to minimize drug resistance.
J Mol Biol 1998 Nov 27
PMID:Structures of Tyr188Leu mutant and wild-type HIV-1 reverse transcriptase complexed with the non-nucleoside inhibitor HBY 097: inhibitor flexibility is a useful design feature for reducing drug resistance. 981 20

Genzyme Molecular Oncology (GMO) is using its SAGE (Serial Analysis of Gene Expression) combinatorial chemistry technology to screen compound libraries. SAGE is a high-throughput, high-efficiency method to simultaneously detect and measure the expression levels of genes expressed in a cell at a given time, including rare genes. SAGE can be used in a wide variety of applications to identify disease-related genes, to analyze the effect of drugs on tissues and to provide insights into disease pathways. It works by isolating short fragments of genetic information from the expressed genes that are present in the cell being studied. These short sequences, called SAGE tags, are linked together for efficient sequencing. The sequence data are then analyzed to identify each gene expressed in the cell and the levels at which each gene is expressed. This information forms a library that can be used to analyze the differences in gene expression between cells [293437]. By December 1999, GMO had identified a set of 40 genes from 3.5 million transcripts that were expressed at elevated levels in all cancer tissue but not seen in normal tissue. The company hope these may provide diagnostic markers or therapeutic targets. The studies also provided data furthering the understanding of the way cells use their genome [349968]. GMO has signed a collaborative agreement with the National Cancer Institute (NCI) to search for new drug candidates in the field of cancer chemotherapy. The collaboration combines GMO's SAGE technology with the NCI's extensive array of 60 cell-based cancer screens. Under the agreement, the NCI will evaluate Genzyme's library consisting of one million compounds against selected cancer screens to identify compounds with anticancer properties [255082]. Xenometrix granted a license agreement for gene expression profiling to GMO in February 1999, giving company access to claims covered in issued US and European patents. The license is non-exclusive and covers the collection of gene expression profiles utilizing all methods including high-density microarrays [315329]. Ontogeny (now Curis Inc) and GMO have entered into a collaboration to study genes for the potential discovery of therapeutic products. GMO will use its SAGE technology to produce libraries of RNA supplied by Ontogeny. The libraries will be put through Ontogeny's screening program [279417]. Under an agreement made in August 1998, Bayer will use SAGE technology to identify genes and thus potential therapeutics [317452]. GMO and Hexagen signed an agreement in March 1998 on the use of SAGE technology in Hexagen's disease gene discovery programs. The first phase of the collaboration will focus on the use of SAGE in studies within Hexagen's type II diabetes gene discovery program. Hexagen has designed these studies to discover susceptibility genes for diabetes and to provide gene expression information for genes associated with type II diabetes [280012]. GMO signed a five-year agreement with Johns Hopkins University School of Medicine (JHU) in July 1997 for research leading to the identification of cancer-related genes. Under the terms of the agreement, JHU researchers will use the SAGE technology to identify and analyze gene expression in cancer. The power of SAGE in finding rare genes was confirmed in a study of gastrointestinal cancer by JHU researchers published in the May 27, 1997 issue of Science. The study showed that of almost 50,000 genes expressed in normal gastrointestinal cells and gastrointestinal tumor cells, 86% of the genes were present at five or fewer copies per cell. Only 51% of those low-abundancy genes were recorded in the GenBank database of known genes in the human genome [257128].
Curr Opin Mol Ther 2001 Feb
PMID:Technology evaluation: SAGE, Genzyme molecular oncology. 1124 36

A. L. Bayer, A. G. Ferguson, P. A. Lucchesi and A. M. Samarel. PYK2 Expression and Phosphorylation in Neonatal and Adult Cardiomyocytes. Journal of Molecular and Cellular Cardiology (2001) 33, 1017-1030. Proline-rich tyrosine kinase (PYK2) is a Ca(2+)-dependent, non-receptor protein tyrosine kinase involved in growth factor signaling. Although PYK2 is expressed in a variety of tissues, it has not yet been identified in cardiac muscle. Therefore, immunocytochemical and Western blotting techniques were used to examine PYK2 expression and phosphorylation in neonatal and adult rat ventricular cardiomyocytes (NRVM and ARVM, respectively). PYK2 concentration was much greater in neonatal, than in adult ventricular tissue and cardiomyocytes. In cultured cells, PYK2 expression was highly dependent on [Ca(2+)](i)transients and contractile activity. Non-contracting, low-density NRVM in serum-free culture expressed very low levels of PYK2, while high-density, spontaneously contracting NRVM showed a approximately 12-fold increase in PYK2 expression. Conversely, high-density NRVM treated with nifedipine (10 microM, 48 h) to block spontaneous [Ca(2+)](i)transients and contractile activity resulted in a 2.6-fold decrease in PYK2 levels. Similarly, overnight culture of quiescent ARVM markedly reduced PYK2 levels. Chronic treatment (48 h) of cultured NRVM with the hypertrophic agonist endothelin-1 (ET) (10-300 n M) did not significantly increase PYK2 levels, but strongly shifted the ratio of phosphorylated to total PYK2, indicating that PYK2 phosphorylation accompanies cardiomyocyte hypertrophy. Endothelin-1 also acutely activated PYK2 in both cultured NRVM, and in freshly isolated ARVM. These results suggest that PYK2 is involved in the generation of certain aspects of cardiomyocyte hypertrophy.
J Mol Cell Cardiol 2001 May
PMID:Pyk2 expression and phosphorylation in neonatal and adult cardiomyocytes. 1134 23

The phospholipid fatty acid composition of the Caribbean gorgonians Gorgonia mariae (Bayer) and Gorgonia ventalina (Linnaeus) is described for the first time. The main phospholipids identified were phosphatidylethanolamine, phosphatidylcholine, and phosphatidylserine. The main fatty acids were 14:0, 16:0, 18:3(n-6), 18:4(n-3), 18:2(n-6), 20:4(n-6), 22:6(n-3), and 24:5(n-6). In both G. mariae and G. ventalina n-6 polyunsaturated fatty acids predominated over the n-3 family. In addition, the 7-methyl-6(E)-hexadecenoic acid was identified in both gorgonians. The occurrence of tetracosapolyenoic fatty acids in the genus Gorgonia is also reported for the first time.
Comp Biochem Physiol B Biochem Mol Biol 2002 Jan
PMID:Phospholipid fatty acid composition of Gorgonia mariae and Gorgonia ventalina. 1174 61

Bayer is developing an IL-2-selective recombinant cytokine, BAY-50-4798, as a potential adjunct to standard chemotherapy in the treatment of various cancers, and for the potential treatment of HIV infection. BAY-50-4798 is currently undergoing phase II clinical trials.
Curr Opin Mol Ther 2004 Apr
PMID:Technology evaluation: BAY-50-4798, Bayer. 1519 35

Phenotypic expression of sickle cell disease (SCD) is highly variable. We investigated red blood cells (RBCs) and reticulocytes using a laser light scattering method (ADVIA120, Bayer Diagnostics, Tarrytown, NY) in a series of patients with either sickle cell anemia (SS) or compound SC heterozygosity (SC), both groups with or without alpha thalassemia. Results were compared with those of a series of patients without hematological disease. Known data were consistently confirmed, namely heterogeneity in cell volume and hemoglobin (Hb) concentration, as well as the premature exit of "stress" reticulocytes from the bone marrow, mostly in SS patients. Specific changes were observed during maturation, including decreases in macrocytic and hypodense cells. Simultaneous viewing of the indices of the different RBC populations provided information on erythropoietic maturation by a rapid, reproducible, and cost-effective method.
Blood Cells Mol Dis
PMID:Automated analysis of mature red blood cells and reticulocytes in SS and SC disease. 1522 5


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