SEARCH · PubMed Health

Results for “ADE”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 721 records · Page 40Linked to original sources

PubMed1982

Nucleic acid metabolism in yeast VI. Utilisation of exogenous dAMP.

It is shown that mutants of Saccharomyces cerevisiae able to efficiently utilise exogenous dTMP can also utilise exogenous dAMP. Under extracellular conditions permissive for dTMP uptake label stemming from offered [8-3H]dAMP is incorporated preferentially into alkali-resistant, high molecular weight material (putative DNA); only about 30% of high molecular weight cell-bound dAMP label was found to be sensitive towards mild alkali hydrolysis. This putative RNA label can be minimised to practically zero when greater than or equal to mM Ade is employed in a dAMP labelling assay. Exogenous dAMP at much greater than 10 microM was found to be cytostatic similarly to much greater than microM dTMP and similarly to inhibit effectively import of exogenous Pi. We conclude from our results that there exists a yeast cytoplasmic membrane permease able to import dAMP. A model of this hypothetical permease system is presented.

Cell Membrane↗

PubMed1988

Further studies on recombination in diploid clones from Bacillus subtilis protoplast fusion.

Diploid prototrophs were obtained from protoplast fusion of Bacillus subtilis strains. They are unstable but upon further cultivation they stabilize retaining diploidy but are genetically inactive. It has been suggested that recombination between the parental chromosomes is involved in the production of stable prototrophs and recombinants. In this work the occurrence of this recombination was searched for by determining genetic linkages in transformation experiments. In prototrophs two alleles: hisH2 and trpE8 carried originally on each parental chromosome, were shown to be 48% co-transformable in a stable clone whereas they were only cotransformed in 10% of the unstable colonies. For Trp- recombinants (the most frequent type of a Leu- Met- Thr- x Ade- Ura- Trp- fusion pair) lysed protoplasts were used as donor DNA for the transformations. High values of co-transfer for Ura+ Met+ were obtained. These results confirm the occurrence of recombination in stable diploid clones, prototrophs or recombinants.

Alleles↗

PubMed1975

Mutations affecting mitotic recombination frequency in haploids and diploids of the filamentous fungus Aspergillus nidulans.

A haploid strain of Asp. nidulans with a chromosome segment in duplicate (one in normal position on chromosome I, one translocated to chromosome II) shows mitotic recombination, mostly by conversion, in adE in a frequency slightly higher than in the equivalent diploid. A method has been devised, using this duplication, for the selection of rec and uvs mutations. Six rec mutations have been found which decrease recombination frequency in the haploid. One mutation selected as UV sensitive showed a hundred fold increase in recombination frequency in the haploid (pop mutation) and probably the same in diploids. The increased frequency is both in gene conversion and in crossing over, and the exchanges appear in clusters of two or more. pop is allelic to uvsB (Jansen, 1970) which had been found to affect mitotic but not meiotic recombination. It is suggested that mutations of this type interfere with the control mechanism which determines that high recombination is confirmed to the meiotic nuclei and avoided in somatic nuclei.

Aspergillus nidulans↗

PubMed1976

Some physiological alteration associated with pleiotropic cross resistance and collateral sensitivity in Saccharomyces cerevisiae.

A mutant strain (2-20) isolated by growth on medium containing oligomycin and cycloheximide was also found to be cross resistant to antimyicn, cerulenin, chloramphenicol, tetracycline, triethyltin and triphenylmethylphosphonium bromide, but collaterally sensitive to dequalinium chloride, gentamycin, neomycin, paromomycin and thiolutin. Growth of 2-20, compared to the parental strain and 2 complete revertants, under a variety of environmental conditions revealed that strain 2-20 had an enhanced sensitivity to increased osmolality, elevated pH, and high temperature; in addition, strain 2-20 was unable to polymerize aminoimidazole ribotide at 37 degrees C as shown by the failure to develop a red colony in the presence of ade 2. Four complex solid media (glucose--KCI, galactose, ethanol, ethanol--KCI, Table 1) unable to sustain the growth of strain 2-20 were arbitrarily chosen to monitor cellular growth under different physiological conditions. Tetrad analysis indicated that the complex phenotype (cross resistance, collateral sensitivity, inablity to polymerize aminoimidazole ribotide, absence of growth under adverse physiological conditions) was inherited by an allele of a locus previously shown to result in a permeability barrier of the plasma membrane to chloramphenicol. 582 of 640 subclones used to isolate revertants of 2-20, under four different physiological conditions, were observed to produce a complete revertant of the complex phenotype. It is proposed that the pleiotropic phenotype could result from an alteration of the plasma membrane and mitochondrial inner membrane by a single nuclear gene mutation.

Alleles↗

PubMed1995

The cycHJKL genes of Rhizobium meliloti involved in cytochrome c biogenesis are required for "respiratory" nitrate reduction ex planta and for nitrogen fixation during symbiosis.

We report the genetic and biochemical analysis of Rhizobium meliloti mutants defective in symbiotic nitrogen fixation (Fix-) and "respiratory" nitrate reduction (Rnr-). The mutations were mapped close to the ade-1 and cys-46 chromosomal markers and the mutated locus proved to be identical to the previously described fix-14 locus. By directed Tn5 mutagenesis, a 4.5 kb segment of the chromosome was delimited in which all mutations resulted in Rnr- and Fix- phenotypes. Nucleotide sequence analysis of this region revealed the presence of four open reading frames coding for integral membrane and membrane-anchored proteins. Biochemical analysis of the mutants showed that the four proteins were necessary for the biogenesis of all cellular c-type cytochromes. In agreement with the nomenclature proposed for rhizobial genes involved in the formation of c-type cytochromes, the four genes were designated cycH, cycJ, cycK, and cycL, respectively. The predicted protein product of cycH exhibited a high degree of similarity to the Bradyrhizobium japonicum counterpart, while CycK and CycL shared more than 50% amino acid sequence identity with the Rhodobacter capsulatus Cc11 and Cc12 proteins, respectively. cycJ encodes a novel membrane anchored protein of 150 amino acids. We suggest that this gene cluster codes for (parts of) a multisubunit cytochrome c haem lyase. Moreover, our results indicate that in R. meliloti c-type cytochromes are required for respiratory nitrate reduction ex planta, as well as for symbiotic nitrogen fixation in root nodules.

Amino Acid Sequence↗

PubMed1985

UV-induced instability in Candida albicans hybrids.

Auxotrophic variants were obtained following UV-irradiation of Candida albicans hybrids which were heterozygous (+/+/-/-/) for various genetic markers (met, ade, his, lys). Some variants contained less DNA (per cell) than did the hybrids from which they originated; such variants were considered to arise in a process which resulted in generalized reduction in ploidy. These results provide the basis for a cyclic parasexual system (2n X 2n----4n----2n) for genetic analysis in this amictic diploid species.

Candida albicans↗

PubMed1977

Induction of mitotic crossing over in Saccharomyces by p-Toluidine.

p-Toluidine, a carcinogen for rats, does not cause genetic damage when tested directly in Saccharomyces cerevisiae; however, certain chemical derivatives of p-toluidine do induce gene conversion when tested directly. It may be suspected by analogy with other aromatic amines that p-toluidine, a monocyclic aromatic amine, requires conversion to breakdown products which are then the genetically active and carcinogenic entities. The Udenfriend hydroxylation medium, which has been used previously to show the genetic activity of certain other aromatic amines and nitrosamines, was used in the incubation of p-toluidine with Saccharomyces cerevisiae. The resulting breakdown products, but not the parent compound, induced reciprocal mitotic recombination in a diploid strain D-3. Recombination was monitored by using induced homozygosity of the red ade 2 marker, and the reciprocal nature of the event was confirmed by observing the simultaneous homozygosity of two peripheral markers.

Biotransformation↗

PubMed1976

The product of the ade1: gene in Schizosaccharomyces pombe: a bifunctional enzyme catalysing two distinct steps in purine biosynthesis.

The assignment of the known ade genes to steps in purine biosynthesis in Schizosaccharomyces pombe has been completed with the demonstration that an ade3 mutants lacks FGAR amidotransferase, ade1A mutants lack GAR synthetase and ade1B mutants lack AIR synthetase. A comparison of enzyme activity with map position for ade1 mutants shows that (1) complementing ade1A mutants lack GAR synthetase but posses wild type amounts of AIR synthetase, (2) complementing ade1B mutants lack AIR synthetase but posses variable amounts of GAR synthetase, (3) non-complementing mutants lack both activities. In wild type strains the two activities fractionate together throughout a hundred-fold purification. Hence the ade1 gene appears to code for a bifunctional enzyme catalysing two distinct steps in purine biosynthesis. The two activities are catalysed by two different regions of the polypeptide chain which can be altered independently by mutation. Gel filtration studies on partially purified enzymes from wild type and various complementing mutant strains, indicate that the bifunctional enzyme is a multimer consisting of between four and six sub-units of 40,000 daltons each. GAR synthetase activity is associated with both the monomeric and multimeric forms but AIR synthetase is only associated with the multimer. A comparison of enzyme levels between diploids and their original complementing haploid strains suggests that complementation is due to hybrid enzyme formation.

Adenine↗

PubMed1992

Genetic analysis of methylotrophic yeast Candida boidinii PLD1.

This paper reports the initial experiments for genetic analysis of the haploid methylotrophic yeast Candida boidinii PLD1. The collection of multiply marked auxotrophic mutants was obtained after treatment with UV-light or X-rays. Protoplasts from several mutants were fused by the PEG-CA2+ technique and five prototrophic hybrids were isolated. The genetic structure of the hybrids was studied by means of spontaneous and induced mitotic segregation. Our data suggest that hybrids are diploids, heterozygous by parental auxotrophic markers. We obtained genetic linkage between mutations lys2-8-met-3 from one hand and ade-17-arg-24 from the other. The genetic maps constructed showed similar characteristics concerning both the order of the markers and their map distances.

Candida↗

PubMed1991

A study on the mechanism of antibody-dependent enhancement of feline infectious peritonitis virus infection in feline macrophages by monoclonal antibodies.

Enhancement of feline infectious peritonitis virus (FIPV) infection of feline macrophages was studied using monoclonal antibodies (MAbs) to the FIPV strain 79-1146. Adherent cells recovered from the feline lung and peritoneal cavity phagocytosed fixed red blood cells, and formed Fc-mediated rosettes. Enhancement of virus infection by MAb was investigated by inoculating alveolar macrophages with a mixtures of viral suspension and MAb, and examining the cells for intracellular viral antigen by the immunofluorescence assay and the amount of infectious virus in the supernatant fluid after incubation. The replication of FIPV in macrophages was enhanced by non-neutralizing MAbs recognizing peplomer protein (S) and transmembrane protein (M) of the virus. Even among the MAbs having the ability to neutralize FIPV strain 79-1146, some reversely enhanced virus infection when they were diluted. The enhancement was suppressed by pretreatment of the MAb with protein A. The enhancement was reduced by the use of F(ab')2 fragment of MAb. These results demonstrated antibody-dependent enhancement (ADE) of FIPV infection in macrophage. The replication of FIPV 79-1146 strain in macrophages from FIPV antibody-positive cats was more enhanced than in those from antibody-negative cats.

Animals↗

PubMed1979

Biochemical genetic analysis of pyrimidine biosynthesis in mammalian cells: III. Association of carbamyl phosphate synthetase, aspartate transcarbamylase, and dihydroorotase in mutants of cultured Chinese hamster cells.

Carbamyl phosphate synthetase (EC 2.7.2.9), aspartate transcarbamylase (EC 2.1.3.2), and dihydroorotase (EC 3.5.2.3), the first three enzymes in de novo pyrimidine synthesis in Chinese hamster ovary cell strain Kl (CHO-Kl), cose diment through a glycerol gradient. When an extract from Urd- A, a pyrimidine-requiring auxotroph reduced in all three activities, is run on a glycerol gradient, the enzyme activities appear in two peaks higher in the gradient, a peak of aspartate transcarbamylase separated from a peak of carbamyl phosphate synthetase and dihydroorotase. Revertants of Urd- A have increased activity of all three enzymes and give glycerol gradient patterns similar to either CHO-Kl or Urd- A. The gradient pattern for Urd- A and some of its revertants can be mimicked by treating the CHO-Kl cell extract with trypsin. Hybrids made between a CHO-Kl purine-requiring auxotroph (Ade- C) and a Urd- A revertant gave a glycerol gradient pattern which is a composite of the CHO-Kl and revertant patterns. A model is presented for the structure of this multifunctional protein.

Amidohydrolases↗

PubMed1991

A need to intensify drug surveillance in Germany.

Despite all its limitations, the spontaneous reporting system still forms the basis for drug safety assessments in the Federal Republic of Germany. Although there have been some promising attempts to standardise the methodology of detecting, analysing and evaluating adverse drug events (ADEs) in certain clinico-pharmacological institutes and psychiatric departments, the approaches have not been integrated and are used only locally. The only exception is the Freiburg Documentation Centre for Severe Skin Diseases, which is attempting comprehensive, country-wide documentation of toxic epidermal necrolysis (Lyell's syndrome) and Stevens-Johnson syndrome. We show that surveillance of 40% of all hospital beds would allow the acquisition of reliable data even on rare and serious AEs which could then be extrapolated in a statistically meaningful way. The medical societies in Germany have traditionally taken a leading role in establishing standards for the preclinical and clinical investigation of new drug compounds. We suggest that they also make it their task to define the framework for an intensified adverse events monitoring system, since it is the patient who ultimately benefits from a quantification of drug therapy risks.

Bed Occupancy↗

PubMed1991

Counterselection of GATC sequences in enterobacteriophages by the components of the methyl-directed mismatch repair system.

Weak to severe deficit of GATC sequences in the DNA of enterobacteriophages appears to be correlated with their undermethylation during growth in dam+ (GATC ade-methylase) bacteria. This observation is corroborated by the sequence analysis showing no evidence for site-specific mutagenicity of 6meAde. The MutH protein of the methyl-directed mismatch repair system recognizes and cleaves the undermethylated GATC sequences in the course of mismatch repair. To enquire whether the MutH function of the methyl-directed mismatch repair system participates in counterselection of GATC sequences in enterobacteriophages, we have studied the yield of bacteriophage phi X174 containing either 0, 1, or 2 GATC sequences, in wild type, dam, and mut (H, L, S, U) Escherichia coli. Following transfection with unmethylated DNA containing two GATC sequences, a net decrease in the yield of infective particles was observed in all bacterial mutH+ dam- strains, whereas no detectable decrease was observed in bacteria infected by DNA without GATC sequence. This effect of the MutH function is maximum in wild type and mutL and mutS bacteria whereas the effect is not significant in mutU bacteria, suggesting an interaction of the helicase II with the MutH protein. However, in dam+ bacteria, the presence of GATC sequences leads to an increased yield of infective particles. The effect of GATC sequence and its Dam methylation system on phage yield in mutH- bacteria reveals that methylated GATC sequences are advantageous to the phage.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗

PubMed1992

Cognitive profile of Alzheimer patients with extrapyramidal signs: a longitudinal study.

The cognitive profile of Alzheimer patients without (ADE-, n = 17) and with (AD, E+, n = 15) extrapyramidal signs (rigidity or bradykinesia), at the time of diagnosis, was examined in a 3-year follow-up study and compared to cognitive performance of demented (PD D+, n = 18) and nondemented (PD D-, n = 17) patients with Parkinson's disease and normal elderly controls (n = 19). Although the AD E+ and AD E- groups did not differ significantly at the initial testing, the AD E+ patients showed greater deterioration on visual, praxic and expressive speech functions as well as in category memory. The cognitive profile of the AD E+ patients was similar to that of the PD D+ patients except that the AD E+ patients recognized more false positive targets on list-learning task. The AD E- patients had better preserved praxic functions and WAIS Performance IQ but they, like AD E+ patients, recognized more false positive targets on list-learning than the PD D+ patients did. The results suggest that AD patients with extrapyramidal signs, even if mild, at the time of diagnosis may have greater progression of cognitive impairment, especially on cortical functions, which may explain earlier need for institutional care observed in previous studies as compared to patients without these signs.

Aged↗

PubMedDate not supplied

New approaches to the rehabilitation of patients with neurological movement defects.

Results were obtained using a new method, based on the "Adeli-92" therapeutic space suit, for the rehabilitation of patients with movement disorders due to acute lesions of the cerebral circulation, head trauma, and other causes. A variety of methods was used to assess the state of patients before and after treatment, including clinical studies, psychological tests, EEG recordings, evoked potential studies, stabilography, and heart rhythm analysis. The results obtained demonstrate the high efficacy of this new method.

Cerebrovascular Disorders↗

PubMed2001

Copper complexes with bioactive ligands Part I--Antimicrobial activity.

Biological properties of new copper(II) complexes of 2-methylthionicotinate (2-MeSNic) of composition Cu(2-MeSNic)2(MeNia)(2).4H2O (where MeNia is N-methyl-nicotinamide), Cu(2-MeSNic)2(Nia)(2).2H2O (where Nia is nicotinamide) and Cu(2-MeSNic)2L2 (where L is isonicotinamide (iNia) or ethyl nicotinate (EtNic)) are reported. Gram(-)-bacteria (Escherichia coli) are more resistant against Cu(II) complexes than Gram(+)-bacteria (Staphylococcus aureus)--significant antistaphylococcal activity was found with Cu(2-MeSNic)2(MeNia)(2).4H2O (IC50 1.3 mmol/L). Candida parapsilosis was most inhibited by Cu(2-MeSNic)2.H2O and Cu(2-MeSNic)2(MeNia)(2).4H2O (IC50 1.4 mmol/L and 1.5 mmol/L, respectively). Biosynthesis of nucleic acids influenced by Cu(2-MeSNic)2(Nia)(2).2H2O indicated by incorporation of 14C-adenine (IC50(Ade) 0.31 mmol/L) is more sensitive than biosynthesis of proteins indicated by incorporation of 14C-leucine (IC50(Leu) 9.94 mmol/L). Cu(II) complexes with expressed antimicrobial activity showed no mutagenic activity.

Anti-Bacterial Agents↗

PubMed2003

Effect of disinfectants on the metabolism of Salmonella enterica serovar enteritidis.

Antimicrobial activity of 19 commercially manufactured disinfectant substances on a Salmonella enteritidis strain was determined. The substances represented 8 quaternary ammonium salts (QAS) and 10 QAS combined with other additives. The antimicrobial efficacy was characterized by influencing the growth of bacterial cells expressed as MIC and ED50 values as well as by the inhibition of the incorporation rate of 14C-adenine and 14C-leucine. According to their efficacy the disinfectants were divided into three groups: (1) substances with strong inhibitory effect (MIC 6-45 micrograms/L) such as Diesin forte, Hexaquart plus, Neoquat S, Triquart, Almyrol, Hexaquart S, ID212, ID213 and Microbac forte; (2) substances with good antibacterial efficacy (MIC 90-780 micrograms/L); (3) substances with MIC values > 780 micrograms/L (up to 3120 micrograms/L). Cetrimide had very low activity (MIC 3.12-6.25 mg/L). The effect of disinfectants on the biosynthetic processes was expressed by R values (IC50(Ade):IC50(Leu)); all these values were < 1 except Benzalkonium chloride, FD312, Divoquat forte, 5P plus, Almyrol, Hexaquart S and Hexaquart plus. Low R values suggested interference of these substances with the synthesis of both nucleic acids and proteins. All substances except 5P plus caused an inhibition of endogenous respiration. The most effective were Almyrol, Diesin forte, Microbac forte and Neoquat which completely inhibited respiration at 190 mg/L. Kvart showed the lowest effect on the respiration over the whole concentration range. The disinfectants also suppressed growth of S. enteritidis, probably by interfering with energy-yielding and-requiring processes in the cells.

Adenine↗

PubMed2002

Progress in the treatment of acute myeloid leukaemia in adults.

There has been important progress in the treatment of Acute Myeloid Leukaemia (AML) in patients under 60 years. A remission rate of 80% can be achieved by several schedules, and 40-45% of patients diagnosed will survive. It may still be possible to improve remission induction treatment eg by intensifying the Ara-C dose although may this only be detectable in an improved disease free survival. The is to reduce relapse. The risk main challenge is pre-determined by a number of powerful risk factors. In the experience of the MRC age, cytogenetics and clearance of blasts from the bone marrow after course 1. Using the later two in combination good risk patients (FAB M3, t(8;21) t(15;17) inv(16)) have a relapse risk of 32%. Poor risk (blasts >15% after course 1 or abnormalities of Chs 5 or 7, 3q- and complex changes have a relapse risk of 82%. All other cases are standard risk and ve a relapse risk of 56%. FLT3 mutations have been detected in about 25% of cases and provide additional negative predictive value overall and within each risk group. The assessment of the most effective consolidation treatment must be made taking into account the heterogeneity of the relapse risk. The MRC investigated the role of allo and autoBMT in addition to intensive chemotherapy. The data was analysis on an intent-to-treat or donor vs no donor basis. Although both types of transplant were able to reduce relapse overall and in all risk groups, there was an overall survival advantage only in standard risk patients. Since chemotherapy has improved since this study, there remains uncertainty about the benefit of transplant in all risk groups. Overall this experience has demonstrated that relapse can be reduced with more therapy. It is probable that the limits of conventional chemotherapy have been reached. The new AML15 trial will assess the value of adding the immunoconjugate (Mylotarg) to induction and/or chemotherapy. Improvements in older patients have been less detectable. MRC trials over the last 20 years show an improvement in remission rate (now 65%) but persistent poor survival (12% at 5 years). In the MRC AML11 Trial three induction schedules were compared (DAT vs ADE vs MAC) with DAT being superior. A comparison of a total of 3 vs 6 courses of treatment or the addition of interferon maintenance did not improve results. Newer approaches currently being assessed include resistance modulation; addition of immunoconjugate and minigrafts. New targets for treatment are emerging of which the most interesting is FLT3 inhibitors.

Acute Disease↗