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Biomedical subjects

C M King

Publications and source records attributed to C M King.

At least 19 recordsLinked to original sources

A practical gloving and handwashing regimen for dental practice.

The debate concerning the re-use of gloves in dental practice continues, despite the fact that recent guidelines on cross-infection control recommend that a new pair of gloves should be used for each patient. Whichever policy for glove use is adopted, it is important to take the maximum possible precautions in hand care. This paper presents a practical regimen for hand/glove washing which is simple, quick and effective. The importance of establishing a hand-care regimen in dental practice is emphasised.

Cross Infection

The demonstration of glomus tumours by subtraction MRI.

Thirteen patients with 14 glomus tumours have been examined by subtraction gadolinium-enhanced magnetic resonance imaging (MRI), with T1-weighted MR sequences before and after intravenous gadolinium-DTPA. To eliminate movement between subtraction pairs, the patient remains in the tunnel of the imager during administration of the contrast medium, and the venepuncture is made into the dorsum of the foot. The effect of the subtraction process is to remove the NMR signal from the final image so that the photographic densities recorded are dependent on the vascularity of the tissue concerned, normal or abnormal. A particular advantage is the removal of fat signal: the low vascularity of adipose tissue ensures that it is recorded as of minimal density. The extent of skull base glomus tumours has been shown optimally by this technique. Subtraction can also help differentiate glomus tympanicum from glomus jugulare lesions, which may be of crucial importance when deciding the surgical approach. In addition to diagnosis, the technique is also important post-operatively, when imaging is needed to show residual or recurrent tumour and to monitor the effects of radiotherapy.

Adult

A double-blind study of superficial radiotherapy in psoriatic nail dystrophy.

In a double-blind controlled study, superficial radiotherapy (SRT) was given to psoriatic fingernails as three fractionated doses of 150 cGy (90 kV, 5 mA, 1.00 mm aluminium filter). The treated nails demonstrated a significant fall in scoring on a clinical rating scale 10 and 15 weeks after therapy (mean scores = 4.4 and 4.6 respectively) when compared with a mean pretreatment score of 5.5 at week 0 (p less than 0.0001 and p less than 0.05 respectively); the treated nails also showed significant clinical improvement when compared with the sham-treated nails at weeks 10 and 15 (p less than 0.05). Mean nail thickness in treated nails 15 weeks after therapy was significantly thinner (mean thickness = 0.75 mm) than that of sham-treated nails (0.88 mm, p = 0.005), but the difference was not significant at week 20. The rate of linear nail growth was unaffected. SRT appears to confer a definite albeit temporary benefit on psoriasis of the nails at this dosage.

Adult

Atopic eczema and orthodontic headgear.

A case is reported where cutaneous irritation by orthodontic headgear was followed by a localized exacerbation of atopic eczema. It is suggested that care should be exercised when considering fitting such an appliance in an individual who suffers from atopic eczema.

Child

Professional paths chosen by past recipients of ASHP Foundation fellowships.

Past recipients of ASHP Foundation fellowships were surveyed to determine their professional activities and the impact of the fellowships on their careers. Questionnaires were mailed to 92 former fellowship recipients. Questions covered the respondents' education and postgraduate training, employment, job and career satisfaction, opinions on the ASHP Research and Education Foundation Fellowships Program, publications and presentations, achievements, experience, honors, and demographics. Respondents returned 77 usable questionnaires, for an 83.7% response rate. Most respondents worked primarily in academia or teaching; one fourth primarily taught. Most of the respondents indicated a positive attitude about both their professional careers and the ASHP Foundation Fellowships Program. Respondents have published (alone or as coauthors) 477 research articles and 359 professional articles; they have given 548 podium presentations and 438 poster presentations at national or regional scientific or professional meetings. Some respondents commented that the program helped them develop needed professional skills and urged that the program be continued. Some suggested that funding be increased to two years and that scoring and selection criteria be revised. Others suggested that the stipend be increased, the results be disseminated, and certain fellowships be re-established. The former ASHP Foundation fellows surveyed have made substantive contributions to the advancement of pharmacy and pharmaceutical science. ASHP Foundation fellowships seem to have favorably affected the professional careers of these fellowship recipients.

Career Choice

Comparative carcinogenicities of 1-, 2-, and 4-nitropyrene and structurally related compounds in the female CD rat.

The comparative carcinogenicities of N-hydroxy-N-acetyl-1-aminopyrene, N-acetyl-1-aminopyrene, and 1-, 2-, and 4-nitropyrene were determined following i.p. injection into weaning female CD rats (67 mumol/kg body weight in dimethyl sulfoxide; 3 times/week for 4 weeks). At sacrifice 61 weeks after the first injection the incidences of malignant mammary tumors were increased significantly to 45 and 24% in the 4-nitropyrene- and N-hydroxy-N-acetyl-2-aminofluorene-treated groups, respectively. Cellular altered foci in the liver were increased significantly in the N-acetyl-1-aminopyrene-, N-hydroxy-N-acetyl-1-aminopyrene-, and N-hydroxy-N-acetyl-2-aminofluorene- treated groups; the latter two compounds also led to significantly increased formation of hyperplastic nodules in this organ. Significant increases in leukemia induction were observed in animals treated with 2-nitropyrene or N-hydroxy-N-acetyl-2-aminofluorene. In an experiment designed to compare the influence of the route of administration on the carcinogenic potential of this agent, 1-nitropyrene was injected i.p. or s.c. into weanling female CD rats (100 mumol/kg body weight; once a week for 4 weeks). The animals were sacrificed at 87 to 90 weeks after the first treatment. The incidences of mammary gland tumors in animals receiving injections of 1-nitropyrene by either route (59%) were significantly higher than in solvent-injected controls (37%). The incidences of adenocarcinoma in the i.p. 1-nitropyrene group (28%) and fibroadenoma in the s.c. 1-nitropyrene group (52%) were significantly higher than in the control animals (7 and 27%, respectively). These data suggest that the demonstration of the weak carcinogenicity of 1-nitropyrene is probably more a function of the length of the observation period than of the routes of administration used here. A further exploration of the effect of the route of administration involved treatment of weanling female CD rats by direct injection of 1-, 2-, or 4-nitropyrene into the mammary fat pads. A total of 2.04 mumol of the nitrocompound in dimethyl sulfoxide was injected into the mammary glands under each of the 6 left nipples. The right mammary glands were treated with the solvent only. Injections of the thoracic nipple areas were carried out on day 1; inguinal areas were treated on day 2. The animals were sacrificed after 77 weeks. The number of mammary tumor-bearing animals (23 of 28), the number with fibroadenoma (15 of 28), and the number with adenocarcinoma (19 of 28) were significantly increased in the 4-nitropyrene-treated group as compared with animals treated with only dimethyl sulfoxide.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma

Acetylation of 2-aminofluorene derivatives by dog hepatic microsomes.

Dog urinary bladder is a target organ of carcinogenic arylamines. However, dog hepatic and urothelial cytosols lack acetylation enzymes that are capable of activating N-hydroxy metabolites of arylamines, suggesting that other enzymes may be involved. In the present study, we found that dog liver microsomes were capable of N-acetylation of 2-aminofluorene and N,O-acetyltransfer of N-hydroxy-2-acetylaminofluorene (N-OH-AAF), and that these activities were inhibited by paraoxon. The 0.25% Triton X-100 extractable fraction of microsomes was resolved on an ion-exchange column into three different proteins that retained these activities. Two of these proteins, designated as enzyme I and enzyme II, were further chromatographed on a Sephacryl S-300 column. As judged from the gel filtration profile, the mol. wt of enzyme I was approximately 180 kDa and that of enzyme II was greater than 700 kDa. SDS-PAGE analysis showed that the subunit weight of enzyme II was approximately 150 kDa. In addition to N-acetylation of 2-aminofluorene and N,O-acetyltransfer of N-OH-AAF, these three enzymes were capable of the deacetylation of 2-acetylaminofluorene, N-OH-AAF and 4-nitrophenyl acetate. The ability of these microsomal enzymes to activate N-hydroxylated aromatic amines and the presence of these enzymes in urothelial cells, reported previously, suggests that they may play an etiological role in the carcinogenicity of these agents in the dog.

2-Acetylaminofluorene

Induction of mutations by N-acetoxy-N-acetyl-2-aminofluorene modified M13 viral DNA.

The specificity of N-(deoxyguanosin-8-yl)-N-acetyl-2-aminofluorene (G-8-AAF) adducts in double-stranded DNAs from M13mp8 and M13mp9 bacteriophage was determined following transfection of modified DNA with multiple adducts into competent JM103 cells. Mutant phages were selected by phenotypic screening for colorless or light blue plaques indicating a defective beta-galactosidase marker enzyme. Mutation frequencies of phage DNA with G-8-AAF adducts were increased up to 8-fold in SOS-induced host cells as compared to the uninduced JM103 host cells. DNA sequencing of mutants from SOS-induced host cells indicated approximately 52% frameshifts and 39% base substitutions in M13mp8 DNA and 65% frameshifts and 25% base substitutions in M13mp9 DNA. Mutation spectra exhibited mutations at many sites within the bp 6200-6400 region; one mutational hotspot at position 6343-6347 (5' GGGGG 3') for frameshifts was also observed. The G-8-AAF adduct induced mostly single base deletions at this site. In contrast, a deacetylated adduct, N-(deoxyguanosin-8-yl)-2-aminofluorene (G-8-AF) in our previous experiments induced mostly single base additions at the same position indicating the ability of adduct structure to modulate the specificity of frameshift mutations. A number of other frameshift mutations (11 out of 29) were observed within non-repetitive and non-palindromic sequences. Molecular mechanisms for the induction of these mutations by DNA perturbations produced by the G-8-AAF adducts are discussed.

2-Acetylaminofluorene

Carcinogenicity of dinitropyrenes in the weanling female CD rat.

The carcinogenicities of 1-nitropyrene and 1,3-, 1,6- and 1,8-dinitropyrene were assessed in weanling female CD rats. The animals were administered one of the compounds at 10 mumol/kg body wt through intraperitoneal or intragastric administration three times a week for 4 weeks. The total cumulative dose averaged 16 mumol/animal. The experiment was ended 78 weeks following the first administration. The average survival period for the animals in the 1,6- and 1,8-dinitropyrene i.p. treated groups, due to the occurrence of life-threatening peritoneal malignant fibrous histiocytomas (MFHs) in nearly all of the animals, were 19 and 38 weeks respectively. 1,3-Dinitropyrene induced only a few MFHs. 1,8-Dinitropyrene also induced a significant incidence of leukemia. A significant increase of the incidence of mammary tumors was observed in the groups of rats treated i.p. with 1-nitropyrene, or 1,3- or 1,8-dinitropyrene, and those treated i.g. with 1,8-dinitropyrene. These results demonstrate that nitropyrenes are capable of inducing MFH, mammary tumors and leukemia in the rat.

Adenocarcinoma

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

Skin problems associated with routine wearing of protective gloves in dental practice.

Guidelines on cross-infection control recommend the wearing of operating gloves by dental practitioners whilst carrying out routine examinations and treatment on all patients. However, there are a number of dermatological problems that may be associated with the routine wearing of protective gloves in dental practice. This paper describes the aetiology and clinical features of three types of contact dermatitis, ie irritant contact dermatitis, allergic contact dermatitis and contact urticaria. The management of these skin conditions is discussed. Advice is given concerning routine handcare for all dental practitioners.

Dentists

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

Comparative survival of aminobiphenyl- and aminofluorene-substituted plasmid DNA in Escherichia coli Uvr endonuclease deficient strains.

pBR322 plasmid DNA, randomly substituted with arylamine moieties, was introduced into Escherichia coli Uvr endonuclease deficient strains. Plasmid survival was determined by selection in the presence of ampicillin. Modification of plasmid DNA with N-acetoxy-N-trifluoroacetylaminobiphenyl yielded primarily N-(deoxyguanosin-8-yl)-4-aminobiphenyl residues. Reaction of DNA with N-acetoxy-N-acetylaminobiphenyl produced only N-(deoxyguanosin-8-yl)-4-acetylaminobiphenyl adducts. The aminobiphenyl (ABP) and acetylaminobiphenyl adducts reduced the ability of the plasmid DNA to transform E. coli to approximately the same extent in a wild-type strain. In uvrA, uvrB and uvrC, i.e. Uvr endonuclease deficient strains, both adducts produced equivalent decreases in survival, however, the reduction in survival was much more pronounced in the uvr- cells than in the wild-type strain. A similar pattern of toxicity was observed with plasmids carrying N-(deoxyguanosin-8-yl)-2-acetylaminofluorene adducts, although the acetylaminofluorene adduct was approximately 5-fold more effective in reducing the biological activity of the plasmid. In contrast, the deacetylated aminofluorene (AF) lesion, N-(deoxyguanosin-8-yl-2-aminofluorene, exhibited relatively little effect on plasmid survival in uvrA and uvrB cells as compared to the wild-type strain, even though the survival of both ABP and AF adducts was essentially similar in the uvrC and wild-type strains. These data demonstrate that (i) both the deacetylated and acetylated lesions are subject to repair by the Uvr endonuclease complex, and (ii) the presence of the N-acetyl group is not the sole determinant of the differential effects of arylamine adducts in uvr cells. These observations provide indirect evidence that both the N-acetyl and aryl moieties of these adducts alter the conformation of DNA.

Acetylation

A case of actinic prurigo and solar urticaria.

Actinic prurigo and solar urticaria are uncommon chronic idiopathic photodermatoses in the United Kingdom. To our knowledge, their occurrence in the same patient has not hitherto been described.

Child

Orofacial granulomatosis associated with delayed hypersensitivity to cobalt.

Orofacial granulomatosis is a distinct clinical and pathological entity characterized by swelling of the lips and lower half of the face. Ulceration of the oral mucosa may also occur. Granulomas are seen histologically. Orofacial granulomatosis may occur in the Melkersson-Rosenthal syndrome, granulomatous cheilitis of Miescher, oral Crohn's disease, sarcoidosis and focal dental sepsis. The increased prevalence of atopy in patients with orofacial granulomatosis and the association with food intolerance suggests the possibility of a role for allergy in at least some cases.

Child