PubMed Health⌕ Search

Biomedical subjects

E Kutter

Publications and source records attributed to E Kutter.

At least 19 recordsLinked to original sources
PubMed2003

Effects of the antibiotic ionophores monensin, lasalocid, laidlomycin propionate and bambermycin on Salmonella and E. coli O157:H7 in vitro.

AIMS: To examine the effects of ionophores on Salmonella and Escherichia coli O157:H7 in pure and mixed ruminal fluid cultures. METHODS AND RESULTS: Four Salmonella serotypes (Dublin, Derby, Typhimurium, and Enteriditis) and two strains of E. coli O157:H7 (ATCC 43895 and FDIU 6058) were cultured in the presence of varying concentrations of ionophores (monensin, lasalocid, laidlomycin propionate, and bambermycin) in pure and mixed ruminal fluid cultures. Bacterial growth rates in pure culture were not affected (P > 0.10) by ionophores at concentrations up to 10 times the approximate rumen ionophore concentration under normal feeding regimens. Likewise, ionophores had no effect (P > 0.10) on Salmonella or E. coli CFU plated from 24-h ruminal fluid incubations. Ionophore treatment decreased (P < 0.01) the acetate : propionate ratio in ruminal fluid cultures as expected. CONCLUSIONS: Ionophores had no effect on the foodborne pathogens Salmonella and E. coli O157:H7 in vitro. SIGNIFICANCE AND IMPACT OF THE STUDY: The results suggest that ionophore feeding would have little or no effect on Salmonella or E. coli populations in the ruminant.

Animals↗
PubMed1998

Comparison of synonymous codon distribution patterns of bacteriophage and host genomes.

Synonymous codon usage patterns of bacteriophage and host genomes were compared. Two indexes, G + C base composition of a gene (fgc) and fraction of translationally optimal codons of the gene (fop), were used in the comparison. Synonymous codon usage data of all the coding sequences on a genome are represented as a cloud of points in the plane of fop vs. fgc. The Escherichia coli coding sequences appear to exhibit two phases, "rising" and "flat" phases. Genes that are essential for survival and are thought to be native are located in the flat phase, while foreign-type genes from prophages and transposons are found in the rising phase with a slope of nearly unity in the fgc vs. fop plot. Synonymous codon distribution patterns of genes from temperate phages P4, P2, N15 and lambda are similar to the pattern of E. coli rising phase genes. In contrast, genes from the virulent phage T7 or T4, for which a phage-encoded DNA polymerase is identified, fall in a linear curve with a slope of nearly zero in the fop vs. fgc plane. These results may suggest that the G + C contents for T7, T4 and E. coli flat phase genes are subject to the directional mutation pressure and are determined by the DNA polymerase used in the replication. There is significant variation in the fop values of the phage genes, suggesting an adjustment to gene expression level. Similar analyses of codon distribution patterns were carried out for Haemophilus influenzae, Bacillus subtilis, Mycobacterium tuberculosis and their phages with complete genomic sequences available.

Bacillus subtilis↗
PubMed1998

The roles of the bacteriophage T4 r genes in lysis inhibition and fine-structure genetics: a new perspective.

Seldom has the study of a set of genes contributed more to our understanding of molecular genetics than has the characterization of the rapid-lysis genes of bacteriophage T4. For example, T4 rII mutants were used to define gene structure and mutagen effects at the molecular level and to help unravel the genetic code. The large-plaque morphology of these mutants reflects a block in expressing lysis inhibition (LIN), the ability to delay lysis for several hours in response to sensing external related phages attacking the cell, which is a unique and highly adaptive attribute of the T4 family of phages. However, surprisingly little is known about the mechanism of LIN, or how the various r genes affect its expression. Here, we review the extensive old literature about the r genes and the lysis process and try to sort out the major players affecting lysis inhibition. We confirm that superinfection can induce lysis inhibition even while infected cells are lysing, suggesting that the signal response is virtually instantaneous and thus probably the result of post-translational regulation. We identify the rI gene as ORF tk.-2, based on sequence analysis of canonical rI mutants. The rI gene encodes a peptide of 97 amino acids (Mr = 11.1 kD; pI = 4.8) that probably is secreted into the periplasmic space. This gene is widely conserved among T-even phage. We then present a model for LIN, postulating that rI is largely responsible for regulating the gpt holin protein in response to superinfection. The evidence suggests that the rIIA and B genes are not directly involved in lysis inhibition; rather, when they are absent, an alternate pathway for lysis develops which depends on the presence of genes from any of several possible prophages and is not sensitive to lysis inhibition.

Amino Acid Sequence↗
PubMed1995

Evolution of T4-related phages.

Much progress has been made in understanding T-even phage biology in the last 50 years. We now know the entire sequence of T4, encoding nearly 300 genes, only 69 of which have been shown to be essential under standard laboratory conditions; no specific function is yet known for about 140 of them. The origin of most phage genes is unclear, and only 42 genes in T4 have significant similarity to anything currently included in GenBank. Comparative analysis of related phages is now being used to gain insight into both the evolutionary origins and interrelationships of these phage genes, and the functions of their protein products. The genomes of phages isolated from Tbilisi hospitals, Long Island sewage plants, the Denver zoo, and Khabarovsk show basic similarity. However, these phages show substantial insertions and deletions in a number of regions relative to each other, and closer investigation of specific sequences often reveals much more complex relationships. There are only a few cases in T4-related phages in which there is evidence for evolution through DNA duplication. These include the fibrous products of genes 12, 34, and 37; head proteins gp23 and gp24; and the Alt enzyme and its downstream neighbors. T4 also contains 13 apparent relatives of group I and group II intron homing endonucleases. Distal portions of the tail fibers of various T-even phages contain segments closely related to tail-fiber regions of other DNA coliphages, such as Mu, P1, P2, and lambda. Horizontal gene transfer clearly emerges as a major factor in the evolution of at least the tail-fiber regions, where site-specific recombination probably is involved in the exchange of host-range determinants.

Amino Acid Sequence↗
PubMed1994

A non-essential domain of Escherichia coli RNA polymerase required for the action of the termination factor Alc.

An evolutionarily nonconserved region of approximately 250 amino acids can be deleted from the amino-terminal part of the beta subunit of Escherichia coli RNA polymerase without effect on the enzyme's basic function. The non-essential segment is located between two highly conserved motifs and is flanked by sequences participating in the rifampicin-binding site. The results define the second non-essential domain in the beta subunit, in addition to the more distal dispensable segment identified previously. The Alc protein of bacteriophage T4 participates in the host transcription shutoff after infection by causing premature termination of transcription on E. coli DNA. Point mutations which prevent Alc action in vivo change amino acids in the non-essential NH2-terminal domain of the beta subunit. These point mutations as well as deletions which remove the non-essential region also prevent Alc action. Thus, in the RNA polymerase molecule, the proximal non-essential domain of beta may function as an acceptor of Alc or other regulatory factors.

Amino Acid Sequence↗
PubMed1993

Bacteriophage T4 Alc protein: a transcription termination factor sensing local modification of DNA.

Bacteriophage T4 Alc protein participates in shutting off host transcription after infection of E. coli. It is demonstrated that Alc acts as a site-specific termination factor. The Alc sites occur frequently in E. coli DNA, resulting in early cessation of elongation in several tested transcription units. Alc-dependent termination requires unimpeded propagation of the elongating complex as it approaches the Alc site. Temporary halting of RNA polymerase within 10-15 bp before the Alc site prevents termination. Bacteriophage T4 transcription is protected from the action of Alc by overall substitution of cytosine with 5-hydroxymethyl cytosine in T4 DNA. In vitro methylation of CpG sequences in the vicinity of an Alc site abolishes the effect of Alc. Thus, Alc-dependent termination involves local sensing of the state of cytosine modification and a short-term "memory" of recent pausing.

Bacteriophage T4↗
PubMed1987

Comparative absorption of zinc picolinate, zinc citrate and zinc gluconate in humans.

The comparative absorption of zinc after oral administration of three different complexed forms was studied in 15 healthy human volunteers in a double-blind four-period crossover trial. The individuals were randomly divided into four groups. Each group rotated for four week periods through a random sequence of oral supplementation including: zinc picolinate, zinc citrate, and zinc gluconate (equivalent to 50 mg elemental zinc per day) and placebo. Zinc was measured in hair, urine, erythrocyte and serum before and after each period. At the end of four weeks hair, urine and erythrocyte zinc levels rose significantly (p less than 0.005, p less than 0.001, and p less than 0.001) during zinc picolinate administration. There was no significant change in any of these parameters from zinc gluconate, zinc citrate or placebo administration. There was a small, insignificant rise in serum zinc during zinc picolinate, zinc citrate and placebo supplementation. The results of this study suggest that zinc absorption in humans can be improved by complexing zinc with picolinic acid.

Administration, Oral↗
PubMed1984

Regulation of a bacteriophage T4 late gene, soc, which maps in an early region.

We have sequenced and analyzed the expression of an early region of the bacteriophage T4 genome that surprisingly contains a late gene, soc. soc is oriented in the same direction as early genes, like the T4 lysozyme gene. Northern hybridization of early and late T4 RNA, using cloned T4 restriction fragments as probes, identified two long early transcripts and a short late transcript, all containing the soc-coding sequence. Thus, soc is transcribed both early and late. It is, however, translated only late. The inhibition of soc translation from the long early transcripts can be explained by formation of a hairpin in the RNA that sequesters the soc ribosome-binding site. The transcript initiated at the late promoter cannot form this hairpin and is, therefore, translated.

Base Sequence↗
PubMed1984

Identification and characterization of the alc gene product of bacteriophage T4.

Bacteriophage T4 infection rapidly and almost completely inhibits transcription of host and other phage DNAs. Two processes have been implicated to date in this inhibition: (1) ADP ribosylation of the alpha subunits of the RNA polymerase, involving gpalt (which is injected with the phage DNA) and, later, gpmod; and (2) the action of the T4 alc/unf gene product, synthesized immediately after infection. The latter unfolds the host genome and also blocks transcription of cytosine-containing DNA. Here, we describe the identification on two-dimensional polyacrylamide gels of gpalc/unf, the more precise mapping of the gene and the identification and analysis of the appropriate DNA sequence from an Unf+ alc mutant.

Amino Acid Sequence↗
PubMed1982

Inhibition of [3H]diazepam and [3H]3-carboethoxy-beta-carboline binding by irazepine: evidence for multiple "domains" of the benzodiazepine receptor.

The binding of [3H]diazepam and [3H]3-carboethoxy-beta-carboline was examined in rat brain synaptosomal membranes treated with irazepine, an alkylating benzodiazepine. Under incubation conditions that resulted in a 25-33% reduction in the Bmax of [3H]diazepam binding, only modest (less than 8.5%) reductions in the Bmax of [3H]3-carboethoxy-beta-carboline were observed. The differential effects of irazepine on the binding of these two compounds may be explained by the presence of multiple areas or "domains" on the benzodiazepine receptor.

Animals↗
PubMed1981

The theory of sets as a tool in systematic drug design.

A strategy of practical drug design is developed on the basis of the theory of sets. This strategy accounts for the fact that new drugs are required to optimally approach a certain activity profile rather than showing maximal intrinsic activity. In addition, modern structure selection techniques as well as qualitative and quantitative structure-activity relationships are incorporated in the strategy so as to optimally contribute to an economical use of experimental capacity.

Chemistry, Pharmaceutical↗
PubMed1981

Application of the theory of sets to drug design. Development of a new cardiotonic drug AR-L 115 BS.

A new type of cardiotonic compounds is developed by applying a systematic drug design procedure based on the theory of sets. With the aid of clinical and pharmacological experience in the field of cardiotonic drugs and from biomolecular considerations a structural field (set) is selected which is likely to contain compounds which show the desired activity profile. By systematic exclusion of inappropriate parts of this structural field (subsets) the original set is reduced to a small structural area (residue set) the structures (elements) of which have a high potential of being new cardiotonic drugs with an activity profile superior to hitherto known compounds. In our case one of the elements, 2-[(2-methoxy-4-methylsulfinyl)phenyl]-1H-imidazo[4,5-b]pyridine (AR-L 115 BS), proved to fulfil all the requirements of the medicinal objective. The structure of AR-L 115 differs significantly from all other cardiotonic principles and therefore represents an entirely new type of positive inotropic agents.

Cardiotonic Agents↗
PubMed1980

A restriction map of the bacteriophage T4 genome.

We report a detailed restriction map of the bacteriophage T4 genome and the alignment of this map with the genetic map. The sites cut by the enzymes Bg/II, XhoI, KpnI, SalI, PstI, EcoRI and HindIII have been localized. Several novel approaches including two-dimensional (double restriction) electrophoretic separations were used.

Chromosome Mapping↗
PubMed1979

A new easily accessible steric parameter for structure-activity relationships.

A simple steric parameter Sb is formulated on the basis of substituent branching. This parameter can be calculated for every conceivable substituent and gives an estimate of steric effects which is sufficient for most purposes in practical drug design. Sb may also be applied to quantitative structure-activity relationships.

Models, Chemical↗
PubMed1977

[Anti-ulcer agent pirenzepine (LS 519)--a tricyclic compound with particular physico-chemical properties (author's transl)].

Compound 5,11-dihydro-11-[(4-methyl-1-piperazinyl)acetyl]-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one dihydrochloride (pirenzepine, L-S 519) represents a new type of drug in ulcer therapy. It has been selected for broad clinical investigations because of its outstanding pharmacological profile. Pirenzepine is devoid of any central activity despite certain structural similarities in relation to psychotropic tricyclic compounds. The extraordinary pharmacokinetic and pharmacodynamic behaviour of this compound can be easily derived from its inherent physicochemical properties: The inability to pass the blood-brain barrier as well as its inability to activate the unspecific and specific psychotropic receptors is due to thermodynamic factors.

Anti-Ulcer Agents↗
PubMed1976

A gene of bacteriophage T4 whose product prevents true late transcription on cytosine-containing T4 DNA.

T-even coliphages have 5-hydroxymethylcytosine in their DNA instead of cytosine. In some T4 mutants, the replicated DNA contains cytosine, but then no late gene products are made. We show that the inability to make late gene products with cytosine-containing T4 DNA is due to a T4 gene products. This gene product, while probably nonessential under normal conditions, interacts with an essential part of the transcription apparatus. Mutations in this gene allow viable T4 particles to be made whose DNA has been substituted almost 100% with cytosine.

Coliphages↗