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T M Reid

Publications and source records attributed to T M Reid.

At least 37 records · Page 2Linked to original sources
PubMed1994

Mutagenesis by metal-induced oxygen radicals.

To assess the contribution of reactive oxygen species (ROS) to metal-induced mutagenesis, we have determined the spectrum of mutations in the lacZ alpha gene after exposure of M13mp2 DNA to Fe2+, Cu2+, and Ni2+. With iron and copper ions, mutations are clustered and are predominantly single-base substitutions. Fe, Cu, and phorbol ester-stimulated neutrophils also produced tandem double CC-->TT mutations. This mutation may provide a marker for the role of oxidative damage in carcinogenesis. Mutagenesis by Ni2+ required the complexing of the metal to a tripeptide and the addition of H2O2. To assess the contribution of ROS in mammalian cells, we determined the spectrum of mutations produced when purified DNA polymerases-alpha and -beta synthesized DNA using a template that had been damaged by ROS. The mutation spectra produced by the two polymerases indicates that these enzymes substitute different nucleotides opposite the same lesions.

Base Sequence↗
PubMed1993

Nickel induces a signature mutation for oxygen free radical damage.

We have determined the specificity of mutations produced by nickel(II), a known human carcinogen, in a forward mutation assay and also used a sensitive reversion assay to show that Ni(II), like iron and copper, can produce tandem double CC-->TT mutations, a hallmark of damage to DNA by either UV irradiation or oxygen free radicals. A reduction in mutation frequencies by the addition of oxygen radical scavengers also supports the involvement of reactive oxygen species in DNA damage and mutagenesis by Ni(II). Mutagenesis by Ni(II) is enhanced by the addition of both hydrogen peroxide and a tripeptide glycyl-glycyl-L-histidine. The enhancement of mutagenesis of Ni(II) by the tripeptide indicates that these complexes could serve to localize Ni(II) in nuclei and mediate DNA damage and mutagenesis via the generation of short-lived oxygen free radicals. These data suggest that Ni(II) carcinogenesis may proceed via the generation of active oxygen species and furthermore provide a model for nickel carcinogenesis based on the binding of Ni(II) to nuclear proteins.

Amino Acid Sequence↗
PubMed1993

Tandem double CC-->TT mutations are produced by reactive oxygen species.

Oxidative damage to DNA is mutagenic and thus may play a role in carcinogenesis. Because of the large number of different DNA lesions formed by oxidative species, no genetic alteration so far identified is exclusively associated with oxygen damage. Tandem double CC-->TT mutations are known to occur via UV damage to DNA and are thought to be a specific indicator of UV exposure. Using a sensitive reversion assay that can detect both single and double mutations within the same codon of the M13-encoded lacZ alpha gene, we show that treatments that produce reactive oxygen species can also produce tandem double CC-->TT mutations. The frequency at which these mutations occur is less than that for single base mutations by a factor of approximately 30. The induction of these mutations is inhibited by treatment that scavenges hydroxyl radicals. This unique mutation provides a marker of oxygen free radical-induced mutagenesis in cells that are not exposed to UV-irradiation and an indicator for assessing the involvement of oxidative damage to DNA in aging and tumor progression.

Base Sequence↗
PubMed1993

Familial cold urticaria. Investigation of a family and response to stanozolol.

BACKGROUND: Familial cold urticaria is a rare cutaneous and systemic reaction to cold with autosomal dominant inheritance, distinctive clinical features, and unknown pathogenesis. Release of a chymotrypsinlike substance has been postulated. To date, no effective treatment has been reported. OBSERVATIONS: Eight cases from a large family pedigree are described. Three members showed a very favorable response in their cold urticaria, when treated with stanozolol; the response was reproducible. Histologic examination of an early lesion in one case revealed evidence of mast cell degranulation. CONCLUSIONS: The biochemical observations are probably secondary epiphenomena. Correction of a deficiency of an inhibitory protein is a possible mechanism of action of stanozolol as in hereditary angioedema.

Adult↗
PubMed1993

Effect of DNA-repair enzymes on mutagenesis by oxygen free radicals.

Cytosine to thymine transitions are among the most common types of mutations produced by oxygen damage to DNA. One possible mechanism for these transitions is deamination of cytosine to uracil. Using both a forward mutation assay as well as a reversion assay specific for damage to cytosines we show that direct deamination to uracil does not play a significant role in mutagenesis induced by reactive oxygen free radicals. In contrast, lesions sensitive to repair by E. coli endonuclease III play a major role in oxidative mutagenesis as evidenced by the ability of endonuclease III to modulate the extent of mutagenesis that results from exposure of DNA to oxygen free radicals.

Cytosine↗
PubMed1993

Aztreonam selective agar for gram positive bacteria.

Aztreonam blood agar, a new selective medium for Gram positive aerobic bacteria, was evaluated in comparison with conventional media for skin swabs. Aztreonam agar increased the number of isolates of Staphylococcus aureus by 17%. By producing purer growths on primary isolation, it significantly speeded up the identification and sensitivity testing of staphylococci and streptococci. All major Gram positive aerobic pathogens grow on this medium. Aztreonam agar is now an established addition to our culture media. It is used for swabs which are likely to have a mixed Gram positive and Gram negative flora, such as ears, burns, ulcers, and for the sputa of patients with cystic fibrosis.

Agar↗
PubMed1992

Mutagenic specificity of oxygen radicals produced by human leukemia cells.

An important source of endogenous oxygen radicals are phagocytic cells such as neutrophils and macrophages. The human leukemia cell line HL-60 can be induced to differentiate into a neutrophil-like cell population. Among the properties of these differentiated cells is the ability to produce reactive oxygen species when stimulated by tumor promoters. Mutagenesis induced by HL-60-generated free radicals was assessed using the M13mp2 forward mutation assay. Single-stranded M13mp2 DNA was coincubated with phorbol ester-stimulated HL-60 cells, after which mutations were scored by transfecting the DNA into SOS-induced Escherichia coli. The mutation frequency was increased 6-fold above background in DNA incubated with HL-60 cells. The majority of the mutations were single-base substitutions. However, approximately 6% of the mutations were tandem double substitutions that occurred in runs of adjacent cytidines. Overall, the mutations were clustered at apparent "hot spots," many of which were similar to sites seen using iron to generate oxygen radicals. These results suggest that human cells able to produce oxygen radicals in response to tumor promoters might play a significant role in the generation of tumors.

DNA, Bacterial↗
PubMed1991

An open study of teicoplanin in the treatment of gram-positive infections.

Teicoplanin, a new glycopeptide antibiotic similar to vancomycin, was evaluated in treating 36 hospitalized patients suffering from various Gram-positive infections. The 36 patients received teicoplanin once daily as a mean intravenous injection of 550 mg/day (range 200-800 mg/day). Previous antimicrobial therapy was used in 28% of patients. The mean duration of therapy was 7.5 days (range 3-38 days). The overall clinical success rate was 94%. 24/36 patients (66%) had positive microbiology. Elimination of the pathogens was seen in 75% of all evaluable cases. Four patients with early prosthetic valve endocarditis due to coagulase negative Staphylococcus (3 patients) and Propionibacterium acnes (1 patient) had a favorable clinical and microbiological outcome. No adverse drug reactions were observed. Teicoplanin is safe and effective in the therapy of many different infections caused by Gram-positive bacteria.

Adult↗
PubMed1991

Accurate in vitro translesion synthesis by Escherichia coli DNA polymerase I (large fragment) on a site-specific, aminofluorene-modified oligonucleotide.

We have measured the accuracy of in vitro synthesis by DNA polymerase I (large fragment) during translesion synthesis past an aminofluorene (AF) adduct. These studies were carried out using a site-specifically modified template which contained a single AF adduct. The template was prepared by first modifying the lone guanine in a 17 base long oligonucleotide and extensively purifying and characterizing this product. The modified 17mer was then ligated to a synthetic duplex to produce a 31 nucleotide long template strand containing the AF adduct annealed to a 14mer, such that the 3'-hydroxyl primer terminus was four nucleotides before the modified guanine. Synthesis on this template by DNA polymerase I efficiently bypassed the AF adduct and produced full-length duplex 31mers. T7 DNA polymerase, on the other hand, was unable to utilize the AF-modified template though it was active on an identical unmodified one. The strand synthesized by DNA polymerase I was then separated from the modified strand, annealed to a complementary oligonucleotide, and the resulting heteroduplex cloned into M13. Each of the 49 clones isolated had sequences which indicated that cytidine had been incorporated opposite the AF-modified guanine.

Base Sequence↗
PubMed1991

Group G streptococcal bacteraemia--a review of thirteen cases in Grampian.

Thirteen cases of group G streptococcal bacteraemia are described. All subjects were hospital in-patients between 1980-1988, and were either middle-aged or elderly. A primary site of infection was identified in 11, of whom nine had soft tissue infection and two had infections derived from the gut/biliary tree. Seven patients had underlying disease, two of whom had malignancy. One patient died of septicaemia. In the majority of patients early institution of treatment led to prompt recovery.

Aged↗
PubMed1991

Salmonella virchow: abscess former amongst the contemporary invasive Salmonellae?

Abscess formation associated with salmonella infections has long been recognized--but without implicating a particular serotype. The pathogenicity, invasiveness and increasingly frequent isolation of Salmonella virchow in the UK is well established. It's propensity to abscess formation is, however, less well recognised. We report 5 patients with abscesses due to S. virchow. This represents a disproportionate number of abscesses in relation to the salmonella isolations in North East Scotland during the 5-year period under scrutiny. We suggest that this organism should be considered as aetiologically relevant even where there is no history of preceding gastrointestinal infection.

Abscess↗
PubMed1991

Piperacillin/tazobactam in the treatment of serious acute soft tissue infection.

Twenty-five consecutive patients admitted to hospital with severe soft tissue infection were entered into an open trial designed to evaluate safety and efficacy of the drug combination tazobactam/piperacillin. The dosage regimen was 4 g piperacillin/500 mg tazobactam Q8H. There were twenty cases of uncomplicated cellulitis and five cases with associated abscess formation. These five cases required adjunctive surgical drainage. Mean duration of therapy was 7.6 days. No other antibiotics were administered unless treatment with the study drug failed. There were eight treatment failures, six related to the trial drug. Four patients developed an allergic response to the trial drug, necessitating a change of therapy. Three patients failed to respond; all three had acute cellulitis in association with peripheral vascular disease. Significant bacterial isolates were grown in thirteen patients; Group A streptococci in three, S. aureus in five, other pathogenic streptococci in four and coliforms or Ps. aeruginosa in five. The majority of isolates except the streptococci were resistant to piperacillin but all isolates except one strain of Ps. aeruginosa were susceptible to the combination. The combination is suitable for the treatment of serious soft tissue infection, but increased doses may be appropriate in infection at poorly perfused sites.

Adolescent↗
PubMed1991

Endogenous mutations and cancer.

We have analyzed two aspects concerning the relationship between mutations and cancer. Firstly, we consider the possibility that spontaneous mutations result from normal cellular processes. Errors in DNA replication, depurination of DNA, and damage to DNA by oxygen free radicals are important potential sources of endogenous mutations. Mutations produced by DNA polymerases in vitro are clustered, and consist predominantly of single-base substitutions. Analysis of termination sites during copying by DNA polymerase-alpha indicates that certain pause sites are associated with misincorporation of single non-complementary nucleotides, and thus pause sites could be associated with mutagenic hotspots. Depurination results predominantly in transversion mutations resultant from the incorporation of deoxyadenosine opposite abasic sites. Mutations resulting from oxygen free radical damage to DNA are predominantly single-base substitutions: C- > T, G- > C, and G- > T being the most frequent. In addition, there is an unusual mutation that results from oxygen free radical damage to DNA, two adjacent cytidines being substituted by two thymidines. The frequency of mutations observed in tumors appears to be much greater than that predicted from the known rates for spontaneous mutagenesis. Recent observations suggest that many human tumors contain four or more independent mutations. If these multiple mutations are each required for tumor development, then the occurrence of malignancies based on normal mutation rates would be exceedingly rare, and it may be necessary to postulate that tumors result from an increase in the rate of endogenous mutagenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Mutagenesis by site-specific arylamine adducts in plasmid DNA: enhancing replication of the adducted strand alters mutation frequency.

Site specifically modified plasmids were used to determine the mutagenic effects of single arylamine adducts in bacterial cells. A synthetic heptadecamer bearing a single N-(guanin-8-yl)-2-aminofluorene (AF) or N-(guanin-8-yl)-2-(acetylamino)fluorene (AAF) adduct was used to introduce the adducts into a specific site in plasmid DNA that contained a 17-base single-stranded region complementary to the modified oligonucleotide. Following transformation of bacterial cells with the adduct-bearing DNA, putative mutants were detected by colony hybridization techniques that allowed unbiased detection of all mutations at or near the site of the adduct. The site-specific AF or AAF adducts were also placed into plasmid DNA that contained uracil residues on the strand opposite that bearing the lesions. The presence of uracil in one strand of the DNA decreases the ability of the bacterial replication system to use the uracil-containing strand, thereby favoring the use of the strand bearing the adducts. In a comparison of the results obtained with site specifically modified DNA, either with or without uracil, the presence of the uracil increased the mutation frequencies of the AF adduct by greater than 7-fold to 2.9% and of the AAF adduct by greater than 12-fold to 0.75%. The mutation frequency of the AF adduct was greatly reduced in a uvrA- strain while no mutations occurred with the AAF adduct in this strain. The sequence changes resulting from these treatments were dependent on adduct structure and the presence or absence of uracil on the strand opposite the adducts.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetamides↗
PubMed1990

Severe salmonellosis related to oral administration of anti-diarrhoeal drugs.

Infection with non-typhoidal Salmonellae usually causes a self-limiting dysenteric illness. Several factors are known to increase the propensity to invasive disease--with its related sequelae. We present four previously healthy patients who had none of the recognised risk factors but developed Salmonella infection with a severe and protracted illness. Common to each of these patients was the pre-hospital oral administration of anti-diarrhoeal drugs.

Adolescent↗