Biomedical subjects
Publications and source records attributed to M V Martin.
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A retrospective study of the incidence of cervicofacial actinomycosis in patients attending the Liverpool Dental Hospital from 1980-1983 was undertaken. A total of 86 patients were found which were divisable into three distinct presentations: acute painful swellings with a duration of less than 1 month; chronic long-standing infections, duration greater than 3 months; unsuspected microbiologically-proven actinomycotic lesions. A prospective study from 1983-1986 also was divisable into three similar types of presentations. The most common presentation in both parts of the study was acute painful swellings associated with soft tissue abscesses secondary to dental lesions. Clinicians dealing with acute dentally-associated swellings should consider the possibility of actinomycosis as a possible diagnosis.
A pilot study was conducted to measure the reported incidence of dry socket following pre-operative irrigation and mouthrinsing with either 0.2% (w/v) chlorhexidine gluconate or normal saline or with no irrigation (control). Three hundred and twenty-four patients presenting for the single extraction of a lower premolar or molar under local anaesthesia were divided into three equal groups; no irrigation, irrigation with saline and irrigation with a 0.2% (w/v) chlorhexidine gluconate solution. After administration of the local anaesthetic agent, 10 ml of the test solutions were applied to the gingival crevice using a blunted needle. The solutions were retained in the patients mouth for 2 min following irrigation. Pre-operative irrigation of the gingival crevice and mouthrinsing with 0.2% (w/v) chlorhexidine gluconate significantly reduced the number of dry sockets. There was no significant reduction in the number of dry socket cases following irrigation and rinsing with normal saline. The irrigation technique, using 0.2% (w/v) chlorhexidine gluconate is safe, inexpensive, easy to apply and can be recommended for routine use in dental practice, to reduce the incidence of dry socket.
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A cDNA sequence related to the human cytochrome P-450 responsible for S-mephenytoin 4-hydroxylation (P-450MP) has been isolated from a human liver bacteriophage lambda gt11 library with antibodies specific for P-450MP. The total length of the cDNA is 2.5 kilobases (kb), of which there is a 1.6-kb EcoRI fragment coding for all but five amino acids corresponding to the N-terminus of the protein and including a small noncoding region at the 3' end. This 1.6-kb fragment has been sequenced and used as a probe to analyze human genomic DNA and liver RNA. The sequence shows extensive sequence similarity with that of rabbit liver cytochrome P-450 progesterone 21-hydroxylase [Tukey, R. H., Okino, S., Barnes, H., Griffin, K. J., & Johnson, E. F. (1985) J. Biol. Chem. 260, 13347-13354], and this cDNA, like the rabbit clone, appears to be part of a multigene family. At least two liver mRNA species, 2.2 kb and 3.5 kb, hybridize to the cDNA sequence. The cloning of this gene should aid in analyzing the molecular basis for the genetic polymorphism of S-mephenytoin 4-hydroxylation reported in humans.
The relationship between experiences with noncontingency and attributional style was examined in experimental and correlational models. One hundred and twenty-six college student subjects were provided noncontingent, contingent, or no feedback as to the correctness of their responses on a concept discrimination problem. They then completed an attributional style questionnaire, a scale designed to measure life experiences with noncontingency, and a depression inventory. The experimental hypothesis was that exposure to noncontingent outcomes, both in a laboratory and historically, would result in more depressive attributions than would exposure to contingent outcomes or to no outcomes. The manipulation of feedback contingencies produced the predicted effect on attributions for positive and negative events combined into a single composite difference score. A correlation between life experiences with noncontingency and attributions was found only for the positive events measure. However, such life experiences were correlated significantly with depression.
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The effect of a palatal acrylic appliance and/or infection with Candida albicans on the permeability of rat palatal epithelium has been investigated. Although normal rats, or rats inoculated with Candida albicans but without a prosthesis, had a barrier to perfused lanthanum, some low-molecular-weight proteins were able to pass through the epithelium. When infection was established by inoculation of Candida albicans under an acrylic plate, the epithelium became permeable to perfused lanthanum. Polyacrylamide gel electrophoresis of perfusates showed that a selective permeability to proteins was retained in such animals. Removal of acrylic plates from infected animals resulted in healing and restoration of the barrier to lanthanum.
The efficacy of cephradine in the prophylaxis of rabbit Streptococcus sanguis endocarditis was investigated. Three days after cardiac catheterization and prior to challenge with S. sanguis, rabbits received either 1000 mg/kg (ten animals) or 500 mg/kg cephradine intramuscularly. Infective endocarditis was prevented in only 30% of the animals. The addition of a second dose of cephradine (100 mg/kg) 8 h after an initial dose of 400 mg/kg did not prevent streptococcal endocarditis in 80% of animals tested. In one or two dose regimens cephradine was found to be inferior to a single 400 mg/kg prophylactic dose of amoxycillin. Cephradine is not recommended for prophylaxis against streptococcal endocarditis.
The efficacy of amphotericin B, 5-fluorocytosine and itraconazole was compared for the treatment of experimental rabbit Aspergillus fumigatus endocarditis. Therapy with amphotericin B or 5-fluorocytosine, at dosages of 3.0 and 35 mg/kg body weight respectively, failed to eradicate aspergillus from the cardiac vegetations in all but one of the animals tested; none of these animals survived for longer than nine treatment days. When similar doses of amphotericin and 5-fluorocytosine were administered concomittantly, 30% of the animals had sterile vegetations. Itraconazole at 2.5 and 3.5 mg/kg body weight was not successful; all the animals tested had infected vegetations and did not survive beyond nine days of therapy. In contrast, itraconazole at 5.0 mg/kg sterilised the endocardial vegetations and all these animals survived for 14 days. It is concluded that itraconazole may be useful in the treatment of aspergillus endocarditis.
The cytochrome P-450 forms involved in debrisoquine 4-hydroxylation (P-450DB), phenacetin O-deethylation (P-450PA), S-mephenytoin 4-hydroxylation (P-450MP), and nifedipine 1,4-oxidation (P-450NF) have been purified to electrophoretic homogeneity from human liver microsomes. All of these reactions show in vivo polymorphism in humans. Evidence for the roles of the purified proteins in these processes comes from in vitro reconstitution and immunoinhibition studies. The rat orthologs of these enzymes are as follows--P-450DB: P-450UT-H; P-450PA: P-450ISF-G; P-450MP: P-450UT-I; P-450NF: P-450PCN-E. Only in the case of P-450UT-H is the primary rat ortholog the same cytochrome P-450 which catalyses the catalytic reaction under consideration. Reconstitution and immunochemical studies establish that the following reactions are catalysed by the individual P-450s--P-450DB: debrisoquine 4-hydroxylation, sparteine delta 5-oxidation, bufuralol 1'-hydroxylation, encainide O-demethylation, and propanolol 4-hydroxylation; P-450PA: phenacetin O-deethylation; P-450MP: S-mephenytoin 4-hydroxylation and tolbutamide methyl hydroxylation; P-450NF: oxidation of nifedipine and 16 other substituted dihydropyridines, estradiol 2- and 4-hydroxylation, aldrin epoxidation, benzphetamine N-demethylation and 6 beta-hydroxylation of testosterone, androstenedione and cortisol. A cDNA clone has been isolated that corresponds to rat P-450UT-H, as shown by a number of criteria. Studies with this probe establish that the sex and strain variation in debrisoquine 4-hydroxylase and related activities is related to differences in the levels of a 2.0 kb length mRNA present.(ABSTRACT TRUNCATED AT 250 WORDS)
A rat liver cDNA library was prepared using the expression vector bacteriophage lambda gt11 and plaques were screened using polyclonal antibodies raised to purified rat liver cytochrome P-450UT-H, the major enzyme involved in debrisoquine 4-hydroxylation, bufuralol 1'-hydroxylation, and sparteine delta 5-oxidation. A clone was selected which contained a 1.3-kb insert. The Escherichia coli beta-galactosidase fusion protein had a molecular weight greater than that of native beta-galactosidase (and reacted with anti-P-450UT-H after electrophoresis) and was also shown to compete with microsomal P-450UT-H for anti-P-450UT-H, partially relieving catalytic inhibition by anti-P-450UT-H in rat liver microsomes. Hybrid selection experiments with the cloned cDNA also support the view that the insert is related to P-450UT-H. mRNA electrophoresis/hybridization experiments indicated that the 1.3-kb cDNA probe recognized primarily only a single size class of mRNA (2.0 kb) in rat liver. mRNA blotting and in vitro translation/immunoprecipitation experiments both indicated that levels of P-450UT-H mRNA are similar in male and female Sprague-Dawley rats. Dark Agouti strain rats of both sexes contained significantly less P-450UT-H mRNA than did Sprague-Dawley rats and the females had approximately one-half the level of the males. These results are consonant with sex and strain differences in measured levels of P-450UT-H and bufuralol 1'-hydroxylase and sparteine delta 5-oxidase activities. Analysis of genomic DNA indicated that several DNA restriction fragments hybridized to this partial length cDNA; no differences were found between the rat strains and sexes. The results suggest that the basis for the variation in P-450UT-H and its activities among rat strains and sexes is at the level of mRNA concentrations.
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The metabolism of the dihydropyridine calcium antagonist and vasodilator nifedipine has been reported to exhibit polymorphism among individual humans (Kleinbloesem, C. H., van Brummelen, P., Faber, H., Danhof, M., Vermeulen, N. P. E., and Breimer, D.D. (1984) Biochem. Pharmacol. 33, 3721-3724). Nifedipine oxidation has been shown to be catalyzed by cytochrome P-450 (P-450) enzymes. Reconstitution, immunoinhibition, and induction studies with rat liver indicated that the forms designated P-450UT-A and P-450PCN-E are the major contributors to microsomal nifedipine oxidation. The P-450 which oxidizes nifedipine (P-450NF) was purified to electrophoretic homogeneity from several human liver samples. Antibodies raised to P-450NF were highly specific as judged by immunoblotting analysis and inhibited greater than 90% of the nifedipine oxidase activity in human liver microsomes. A monoclonal antibody raised to the human P-450 preparation reacted with both human P-450NF and rat P-450PCN-E. Immunoblotting analysis of 39 human liver microsomal samples using anti-P-450NF antibodies revealed the same 52,000-dalton polypeptide, corresponding to P-450NF, with only one of the microsomal samples showing an additional immunoreactive protein. The level of nifedipine oxidase activity was highly correlated with the amount of P-450NF thus detected using either polyclonal (r = 0.78) or monoclonal (r = 0.65) antibodies, suggesting that the amount of the P-450NF polypeptide may be a major factor in influencing the level of catalytic activity in humans as well as rats. Cytochrome b5 enhanced the catalytic activity of reconstituted P-450NF, and anti-cytochrome b5 inhibited nifedipine oxidase activity in human liver microsomes. P-450NF also appears to be a major contributor to human liver microsomal aldrin epoxidation, d-benzphetamine N-demethylation, 17 beta-estradiol 2- and 4-hydroxylation, and testosterone 6 beta-hydroxylation, the major pathway for oxidation of this androgen in human liver microsomes.
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