Respiratory tract penetration of ciprofloxacin.
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Adult↗
Biomedical subjects
T M Reid
Publications and source records attributed to T M Reid.
Mutagenesis by single site-specific arylamine-DNA adducts. Induction of mutations at multiple sites.
Two related carcinogen adducts, N-(deoxyguanosin-8-yl)-2-aminofluorene (AF) or N-(deoxyguanosin-8-yl)-N-acetyl-2-aminofluorene (AAF), were introduced into the lacZ' gene at base position 6253 of the minus strand of M13mp9 viral DNA. The construction of this site-specifically modified DNA was accomplished by first preparing a gapped heteroduplex missing 7 nucleotides at position 6251-6257 followed by ligation with an unmodified heptamer or with a heptamer containing either an AF or AAF adduct. These site-specifically modified templates were transfected into competent wild-type Escherichia coli cells (JM103) and a uvrA strain (SMH12). The mutation spectrum was determined by phenotypic selection of colorless plaques indicating a defective beta-galactosidase marker enzyme and by an in situ hybridization procedure to detect single base pair mismatches in the adduct region. DNA sequencing was used to characterize 179 of the mutants obtained. We found that both adducts were capable of inducing base substitution mutations at the adduct site and in the local region of the adduct. A specific frameshift (+1G) was also observed at a displaced site. All of the frameshift mutations occurred at the ligation site of the modified oligonucleotide. Control experiments with an unmodified oligonucleotide did not show an enhancement of mutations at this site, indicating that the adducts may have been responsible for these frameshifts. The mutations spectra induced by these adducts suggest that mutagenesis depends not only on adduct structure but also the sequence in which the adduct is located and the host cell type used for mutation expression.
2-Acetylaminofluorene↗
Mutations induced by aminofluorene-DNA adducts during replication in human cells.
To gain insight into the mechanisms by which carcinogens induce mutations in human cells, we treated a shuttle vector, pZ189, carrying the supF gene as the target for mutations with N-acetoxy-N-trifluoroacetyl-2-aminofluorene (N-AcO-TFA-AF). The plasmids were allowed to replicate in human cell line 293, and the progeny plasmids were examined for the frequency and kinds of mutations induced in supF, as well as their specific location in the sequence of the supF gene. The plasmids were reacted with N-AcO-TFA-AF so as to obtain the deacetylated adduct N-(deoxyguanosin-8-yl)-2-aminofluorene (dG-C8-AF), the principal adduct formed in DNA when mammalian cells are exposed to reactive derivatives of 2-acetylaminofluorene (AAF), including N-acetoxy-2-acetylaminofluorene. The results showed there was a linear relationship between the number of dG-C8-AF adducts per plasmid and the frequency of supF mutants induced. DNA sequencing of 47 independent mutants obtained from doses of N-AcO-TFA-AF that increased the frequency of mutants 9-15 times the background frequency and three independent mutants from lower doses showed that 92% contained point mutations, i.e. changes affecting one, or two, or three nearby bases, and that all of these point mutations involved G.C base pairs. Ninety eight percent of the point mutations were base substitutions, predominantly G.C----T.A transversions. 46% of these mutations occurred at four out of the 85 bp in the target gene (hot spots). The most prominent mutation hot spot was also the most prominent hot spot for adduct formation as judged by the frequency of termination of in vitro polymerization by the Klenow fragment on N-AcO-TFA-AF-treated plasmids.
2-Acetylaminofluorene↗
Clinical and pathological variability of infection by enterohaemorrhagic (Vero cytotoxin producing) Escherichia coli.
The clinical and pathological features of five sporadic cases of enteric infection caused by Escherichia coli O157 (enterohaemorrhagic or Vero cytotoxin-producing E coli showed a range of features. These included one case with pseudomembranous colitis, one with an acute exacerbation of ulcerative colitis, and three with enterocolitis. Diagnostic difficulties encountered initially in four of the five cases were finally resolved by correlating the results of microbiological with histopathological investigations. In view of the heterogeneity of clinical and histological signs and symptoms, it is concluded that all patients with abdominal pain and diarrhoea or rectal bleeding should have early microbiological investigation.
Adult↗
Amoxycillin/clavulanic acid levels in respiratory secretions.
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Amoxicillin-Potassium Clavulanate Combination↗
Food poisoning due to the consumption of red whelks (Neptunea antiqua).
Two incidents of toxin-type food poisoning in N.E. Scotland associated with the consumption of red whelks (Neptunea antiqua) are described. Four patients developed symptoms within 1 h of consuming whole whelks. These included visual disturbances--double vision and difficulty in focusing--tingling of the fingers, prostration and in one subject nausea, vomiting, diarrhoea and ataxia. In all cases recovery was complete in 24 h. Using a newly developed analytical technique the concentration of the causative toxin, tetramine, in the salivary glands of the whelks consumed was estimated at 0.07%, equivalent to a content of 3.75 mg/100 g of the shellfish.
Adult↗
Amoxycillin/clavulanic acid levels in lower respiratory secretions.
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Amoxicillin↗
Imipenem versus standard therapy in the treatment of serious soft tissue infection.
Thirty-five patients with 36 episodes of serious soft tissue infection were entered in a prospective randomised trial to receive treatment with either intravenous imipenem or standard therapy, most commonly i.v. cloxacillin and benzylpenicillin. Eighteen patients received imipenem (Group 1) and eighteen standard therapy (Group 2). In Group 1, fourteen patients were cured, one improved and three failed therapy. The three failures comprised two where imipenem had to be stopped because of side-effects and one changed to standard therapy after 48 h because of lack of response. In Group 2, fourteen patients were cured, three improved and one failed therapy. This last case was due to lack of clinical response. Tolerance of both drugs was good, although eight patients in Group 1 versus none in Group 2 developed infusion phlebitis. All significant bacterial isolates were sensitive to imipenem, although several were resistant to cloxacillin and/or benzylpenicillin. No development of bacterial resistance was noted in isolated pathogens. There was no significant difference in rapidity of response or length of treatment between Groups 1 and 2. Imipenem is a safe and effective alternative to standard regimens in the treatment of serious soft tissue infection, although its side-effects and broad spectrum make it difficult to justify its use for uncomplicated cellulitis.
Abscess↗
Evidence for in vitro translesion DNA synthesis past a site-specific aminofluorene adduct.
The ability of Escherichia coli DNA polymerase I and T7 DNA polymerase to bypass bulky C-8 guanyl-2-aminofluorene adducts in DNA was studied by in vitro DNA synthesis reactions on a site-specific aminofluorene-modified M13mp9 template. This site-specifically modified DNA was prepared by ligating an oligonucleotide containing a single aminofluorene adduct into a gapped heteroduplex of M13mp9 DNA (Johnson, D. L., Reid, T. M., Lee, M.-S., King, C. M., and Romano, L. J. (1986) Biochemistry 25, 449-456). The resulting covalently closed duplex DNA molecule was then cleaved with a restriction endonuclease, denatured, and annealed to a primer on the 3' side of the adduct to form a template specifically designed to study bypass. In this system, any synthesis that was not blocked by the bulky aminofluorene adduct would proceed to the 5' terminus of the single-stranded template, while synthesis interrupted by the adduct would terminate at or near the adduct location. We have measured DNA synthesis on this template and find that the amount of radiolabeled nucleotide incorporated by either E. coli DNA polymerase I (large fragment) or T7 DNA polymerase was much greater than would be predicted if the aminofluorene adduct were an absolute block to DNA synthesis. Furthermore, the products of similar reactions electrophoresed on polyacrylamide gels showed conclusively that the majority of the DNA synthesized by either the T7 DNA polymerase or E. coli DNA polymerase I bypassed the aminofluorene lesion. Substitution of Mn2+ for Mg2+ as the divalent cation resulted in even higher levels of translesion synthesis.
2-Acetylaminofluorene↗
Effect of topical and systemic antibiotics on bacterial growth kinesis in generalized peritonitis in man.
Quantitative bacteriology in peritoneal exudate was studied in 40 patients with generalized peritonitis of small intestinal, appendicular or colonic origin. Bacterial growth kinesis was measured in 28 of the patients. Systemic antibiotics given before operation resulted in a significant reduction in both the concentration and growth rate of viable bacteria in the peritoneal fluid. Lavage of the peritoneal cavity with saline resulted in a further reduction in growth rate in patients given pre-operative systemic antibiotics by an effect attributable to simple dilution. In contrast, peritoneal lavage with tetracycline (1 mg/ml) resulted in complete inhibition of bacterial growth in the residual peritoneal fluid. These observations support the policy of giving systemic antibiotics to patients with generalized peritonitis as soon as the diagnosis has been made and provide bacteriological evidence for the value of peroperative antibiotic peritoneal lavage.
Anti-Bacterial Agents↗
Antibiotic prophylaxis in non-perforated appendicitis of childhood: tetracycline lavage compared with peroperative intravenous cefuroxime and metronidazole.
Eighty-four cases of non-perforated appendicitis in children were randomly allocated to receive either oxytetracycline lavage alone or oxytetracycline lavage plus peroperative intravenous metronidazole and cefuroxime. The wound infection rate with the oxytetracycline lavage alone was 4.4% compared with 7.7% when metronidazole and cefuroxime were added. These rates were not significantly different. This study supports the use of oxytetracycline lavage alone as effective prophylaxis against wound infection in non-perforated appendicitis of childhood.
Adolescent↗
Reduced synthetic activity as a contributing factor to weight-loss in the circannual cycle of Richardson's ground squirrels.
1. Glycogen concentrations in Richardson's ground squirrels of the weight-loss phase were 1/4-1/2 those in animals of the weight-gain phase. White adipose lipid content was similar in animals in the two phases when total body weight was similar. 2. Specific activity of 14C in muscle glycogen of fed, starved and refed ground squirrels in the weight-loss phase was similar to that in starved weight-gain phase animals. Activity in adipose lipids of fed, starved, and refed ground squirrels in the weight-gain phase was 5-8 times greater than that in the same nutritional states in weight-loss phase animals. 3. In addition to a voluntary reduction in food intake, a depressed synthetic activity in lipids and glycogen may account in part for the rapid decrease in body weight during the weight-loss phase of the circannual cycle.
Adipose Tissue↗
Frozen raspberries and hepatitis A.
An outbreak of 24 cases of hepatitis A in Aberdeen was traced to a large hotel in the city by epidemiological investigation. Food-specific questioning of those affected, their fellow diners and hotel staff, coupled with serological studies, implicated raspberry mousse prepared from frozen raspberries as the source of the infection. The raspberries were probably contaminated at the time of picking.
Antigens, Viral↗
Chemical stability of oligonucleotides containing the acetylated and deacetylated adducts of the carcinogen N-2-acetylaminofluorene.
We have prepared and characterized the single-stranded oligonucleotide heptamer 5'-ATCCGTC-3' in which the lone guanine of the oligonucleotide is modified at the C8 position with either the acetylated or deacetylated form of the carcinogenic adduct 2-aminofluorene. These two lesions represent the two major adducts formed upon the in vivo administration of the potent experimental carcinogen N-2-acetylaminofluorene. The stability of the adducts was compared by analyzing the oligonucleotide for strand scission or depurination by polyacrylamide gel electrophoresis following treatment under either neutral, acidic or basic conditions or incubation in the presence of piperidine. The results show that both adducts are stable near neutral pH but that the deacetylated adduct is less stable than the acetylated adduct to either basic or acidic conditions. Both adducts are equally susceptible to piperidine. The method of analysis described here could prove useful for characterizing other adduct structures, thus providing a general procedure to determine the stability of a variety of lesions in DNA.
2-Acetylaminofluorene↗
Penicillin in milk--its importance in urticaria.
Fifty patients with recurrent urticaria were tested by means of the RAST test for penicillin allergy. Fifteen patients had positive reactions and of these, thirteen received provocation tests with 0.1 U/ml of penicillin in milk. Four had definite positive reactions, three doubtful reactions and six had no reaction. Although there has been improvement in the purity of milk, penicillin residues remain a potential cause of urticaria even in very low amounts and could have contributed to the urticaria in at least 8% of our patients. Veterinary use of antibiotics and food quality should be strictly regulated to prevent contamination of our diet.
Adult↗
Preparation and characterization of a viral DNA molecule containing a site-specific 2-aminofluorene adduct: a new probe for mutagenesis by carcinogens.
The synthetic oligonucleotide heptamer 5'-ATCCGTC-3' was reacted in vitro with N-acetoxy-N-(trifluoroacetyl)-2-aminofluorene and the resulting product isolated by reverse-phase high-performance liquid chromatography (HPLC). This purified oligonucleotide, which was shown by chemical and enzymatic analysis to be a heptamer containing a single N-(deoxyguanin-8-yl)-2-aminofluorene adduct, was then used to situate the putatively mutagenic aminofluorene lesion within the genome of M13 mp9 by ligating it into a complementary single-stranded region located at a specific site in the negative strand of the duplex M13 mp9 DNA molecule. The presence of the adduct at the anticipated location was confirmed by taking advantage of the facts that AF adducts inhibit many restriction enzymes when located in or near their restriction sites and that the AF moiety should be contained within the HincII recognition sequence on M13 mp9 DNA. Upon attempted cleavage of the M13 DNA containing the site-specific AF adduct with HincII, we find that the large majority of the DNA remained circular, demonstrating the incorporation of the AF adduct in high yield into the DNA molecule at this location. This system should prove useful in vivo for the study of mutagenesis by chemical carcinogens and in vitro to study the interaction of purified DNA metabolizing proteins with a template containing a site-specific lesion.
Base Sequence↗
Molecular epidemiology of human rotavirus.
The epidemiology of human rotavirus (HRV) in north-east Scotland was investigated between 1982 and 1984. During this period 708 HRV infections were recorded. The majority (83%) of the infections were in children less than 5 years of age although some were recorded in adults. The peak incidence occurred in the winter months although a high number of HRV infections was reported during the summer of 1983. A total of 840 faecal specimens containing rotavirus were screened for HRV genome RNA by polyacrylamide gel electrophoresis. Seven hundred (83%) specimens gave RNA profiles suitable for establishing the HRV electrophoretype. Twenty-five different electrophoretypes were identified, of which 21 had 'long' RNA profiles and four had 'short' RNA profiles. There was extensive co-circulation of distinct electrophoretypes although during any one epidemic period the majority of viruses belonged to a relatively small number of types. Comparison of viruses collected from hospitalized and non-hospitalized patients showed no differences in electrophoretype distribution. HRV was identified in faecal specimens from a wide age group and no correlation was demonstrated between age of patient and electrophoretype of the infecting virus.
Adolescent↗
Salmonella reactive arthritis: serum and secretory antibodies in eight patients identified after a large outbreak.
Serial measurements of serum and secretory antibodies to Salmonella typhimurium were made by ELISA in eight patients with suspected reactive arthritis identified after a large outbreak of Salmonella gastroenteritis. All three patients from whom Salmonella had been isolated developed significant serum IgG, IgA and IgM antibody responses. Only one of the three possessed HLA-B27. A further three patients, two with HLA-B27, had raised antibodies, although none had experienced gastroenteritis. Salmonella infection was not confirmed in the remaining two patients. The three B27-negative patients with confirmed reactive arthritis had HLA-B locus antigens which serologically cross-react with B27. One of six patients with confirmed reactive arthritis was under the age of 25 years whereas 256 of 418 (61%) patients with uncomplicated enteritis were under this age. The development of reactive arthritis may follow subclinical Salmonella infection and is influenced by genetic and age-related factors.
Adult↗