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Biomedical subjects

M V Martin

Publications and source records attributed to M V Martin.

At least 127 records · Page 7Linked to original sources
PubMed1986

Effect on experimental palatal candidosis in the Wistar rat of removal and re-insertion of acrylic appliances.

Palatal candidosis was produced by inoculating Candida albicans 3091 (serotype A) under an acrylic appliance. Two weeks was allowed for infection to occur. Removal of the appliance for a further period of 2 weeks resulted in complete resolution of the lesion histologically but Candida organisms could still be recovered from the mucosal surface. Re-fitting these appliances at the end of this recovery period, without subsequent inoculation, produced a recrudescence of palatal candidosis after a further 2 weeks. One possible explanation is that C. albicans was encouraged to change from the commensal to the pathogenic form in the presence of the palatal appliance.

Animals↗
PubMed1986

Epithelial mitotic activity during the induction of palatal candidosis in the Wistar rat.

Palatal candidosis was produced in 15 Wistar rats by fitting them with an acrylic appliance that covered the palatal mucosa and simultaneously inoculating this site with Candida albicans 3091 (serotype A). A further 15 rats were fitted with the appliance only. Five animals in each group were killed at 1, 2 and 4 weeks, 4 X 5 h after being injected with vinblastine sulphate, as were 5 normal control animals at the start of the experiment. Palatal mucosa was dissected free, fixed, sectioned and stained prior to counting the number of arrested mitotic figures in the basal epithelial layer and measuring the mean thickness of epithelium. The results were expressed as the number of mitotic figures per 1000 basal cells, per unit length of basement membrane and per square millimetre of epithelial surface. After an initial reduction in thickness, the palatal epithelium in both experimental groups became thicker than that of normal control animals, more markedly so in the animals infected with Candida albicans. Similar patterns of mitotic activity were found regardless of the reference unit used as a basis for the calculations. An initial decrease in both experimental groups was followed by a sharp and significant rise, again being more marked in the animals infected with Candida albicans.

Animals↗
PubMed1986

Human-liver cytochromes P-450 involved in polymorphisms of drug oxidation.

Nine forms of cytochrome P-450 have been purified to electrophoretic homogeneity from human-liver microsomes. These include the enzymes involved in debrisoquine 4-hydroxylation, phenacetin O-deethylation and mephenytoin 4-hydroxylation, three reactions which are characterized by genetic polymorphism in humans. Evidence for the involvement of the above enzymes comes from reconstituted immunochemical inhibition studies with human-liver microsomes. These and other lines of evidence are consonant with the view that different forms of cytochrome P-450 are involved in the three reactions. The debrisoquine 4-hydroxylase has been studied most extensively in terms of its substrate specificity. In addition, an analogous rat enzyme shows some homology and serves as a useful model. The use of antibodies raised to the rat-liver enzyme in immuno-inhibition studies with human-liver microsomes provides a means of determining the extent to which this enzyme participates in other reactions. Translation of rat-liver mRNA in vitro yields the intact debrisoquine 4-hydroxylase; studies with human mRNA suggest a lower frequency than in rats. The basis for impaired catalytic activity in phenotypically poor human metabolizers appears to be an altered enzyme in all three cases, as opposed to a decreased level of a single enzyme. Using antibody screening of fusion proteins expressed in a cDNA library, it has been possible to isolate cDNA probes for all three of these cytochromes P-450 for use in screening individuals and ultimately determining the basis of these polymorphisms.

Binding Sites↗
PubMed1986

The effects of Candida albicans on turpentine-induced hyperplasia of hamster cheek pouch epithelium.

This investigation aimed to determine the effect of Candida albicans on hyperplastic epithelium. Epithelial hyperplasia was induced in hamster cheek pouches by painting the mucosa with 50% (v/v) turpentine and liquid paraffin (TLP50) for 10 weeks. The pouches were then tied off with sutures after inoculation with C. albicans. Many of the pouches lost their sutures and were histologically normal after periods up to 8 weeks. Those which remained tied off showed epithelial dysplasia resembling changes seen in human candida leukoplakia. It is suggested from these preliminary experiments that C. albicans may be capable, in certain conditions, of causing further changes to hyperplastic epithelium resembling those seen in Candida leukoplakia.

Animals↗
PubMed1985

Purification and characterization of the human liver cytochromes P-450 involved in debrisoquine 4-hydroxylation and phenacetin O-deethylation, two prototypes for genetic polymorphism in oxidative drug metabolism.

Two forms of cytochrome P-450 were purified to apparent homogeneity from several different preparations of human liver microsomes. One form, designated P-450DB, had relatively high catalytic activity towards the drugs debrisoquine, sparteine, bufuralol (both the (+)- and (-)-isomers), encainide, and propranolol and appears to be the enzyme involved in the polymorphic distribution of oxidative activities towards these substrates in humans. The other form, designated P-450PA, had relatively high phenacetin O-deethylase activity and appears to be involved in the variation of this activity among humans. Polyclonal antibodies raised to the two enzymes were specific for the antigens as judged by immunoelectrophoresis and immuno-inhibition studies. The two enzymes and their activities were distinguished by chromatographic separation, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, amino acid composition, immuno-inhibition studies, and steady-state kinetic assays. Immunochemical studies suggest that each form represents only a small fraction of the total cytochrome P-450 in human liver microsomes. These biochemical studies provide a basis for better understanding the mechanisms which underlie genetic polymorphisms involving P-450 cytochromes in humans.

Amino Acids↗
PubMed1985

Antibiotic treatment of cervicofacial actinomycosis for patients allergic to penicillin: a clinical and in vitro study.

The minimum inhibitory concentrations for erythromycin, clindamycin, lincomycin, tetracycline and minocycline have been determined for 92 clinical and three culture collection isolates of Actinomyces. From a consideration of MIC values and expected serum levels from oral therapy, minocycline was the drug of choice for the treatment of actinomycosis in patients allergic to penicillin. The serum levels of six patients allergic to penicillin, treated with oral minocycline 1 g/day were monitored and found to exceed the MIC for the Actinomyces species responsible for the condition. In all six Actinomycosis cases resolution was achieved in 8-16 weeks of oral minocycline therapy with no recrudescence for 1 year.

Actinomyces↗
PubMed1985

Candida glabrata (syn. Torulopsis glabrata) associated with a chronic hyperplastic lesion of the palate.

A case initially presenting as chronic hyperplastic candidosis is described. After treatment with nystatin on three separate occasions over a seven-year period, a lesion similar to that diagnosed originally occurred in the same site. Further examination of this later occurrence showed it to be associated with the imperfect fungus Candida glabrata which had a high minimum inhibitory concentration for nystatin (greater than 30 micrograms/ml). The lesion eventually resolved following treatment with miconazole gel and surgical excision of the hyperplastic tissue. The patient has remained symptomless for a two-year follow-up period.

Adult↗
PubMed1985

Resistogram typing of Candida albicans isolates from oral and cutaneous sites in irradiated patients.

Thirteen resistogram strains of Candida albicans were found among isolates obtained from the mouth and cutaneous sites of irradiation of 27 patients receiving treatment for oral and laryngeal cancer. In all cases the yeast was recovered from the mouth before treatment, but not from the skin site until after treatment had begun. Of the 27 patients, 25 harboured one or more strains with identical resistograms in both sites.

Adult↗
PubMed1985

Substrate specificity of human liver cytochrome P-450 debrisoquine 4-hydroxylase probed using immunochemical inhibition and chemical modeling.

A significant population of humans (5 to 10%) are phenotypic poor metabolizers of debrisoquine. We have isolated the cytochrome P-450 isozyme from rat liver responsible for this activity and have shown that antibodies raised against the protein are able to inhibit this catalytic activity in human liver microsomes (Distlerath, L. M., and Guengerich, F. P., Proc. Natl. Acad. Sci. USA, 81: 7348-7352, 1984). These antibodies were utilized to determine which metabolic transformations are linked to debrisoquine 4-hydroxylation in human liver microsomes using techniques of immunochemical inhibition. The antibodies almost completely inhibited debrisoquine 4-hydroxylation and bufuralol 1'-hydroxylation in microsomes prepared from several different human livers. The oxidation of the pyrrolizidine alkaloids lasiocarpine and monocrotaline were inhibited by roughly one-third. The antibodies did not inhibit N,N-dimethylnitrosamine N-demethylation, oxidation of vinylidene chloride to 2,2-chloroacetaldehyde, oxidation of trichloroethylene to chloral, N-oxidation of azoprocarbazine, morphine N-demethylation, diazepam N-demethylation, oxidation of benzo(a)pyrene to alkali-soluble metabolites, oxidation of benzo(a)pyrene 7,8-dihydrodiol to products covalently bound to DNA, the N- and ring-oxidation of 1- and 2-naphthylamine and 2-aminofluorene, or the conversion of aflatoxin B1 to DNA adducts or aflatoxin Q1. Studies with space-filling models of the drugs the metabolism of which is associated with debrisoquine 4-hydroxylase in the literature indicated that all can be fitted to a general structure in which a basic nitrogen is about 5 A away from the site of carbon hydroxylation and a hydrophobic domain is near the site of hydroxylation. These results may be useful in predicting which chemicals may or may not be metabolized in an atypical manner by a segment of the human population.

Aflatoxin B1↗
PubMed1984

A pilot study of the clinical effects of irradiation on the oral tissues.

The clinical effects of irradiation on the oral mucous membrane of 22 patients with oral or circumoral carcinomas (oral group) were compared with nine patients with laryngeal carcinomas (laryngeal group). Each of the patients received 6000 rads of radiation in divided doses five days each week for five weeks, alternately left and right sides. After one week of irradiation, patients in the oral group had diminished salivary flow, some erythema and orally-derived pain. After three weeks, severe clinical changes were present and these changes increased throughout the treatment period. Four to six months after treatment, the majority of the clinical changes had resolved in the oral group but salivary flow from parotid and submandibular/sublingual glands was still diminished. The laryngeal group had few clinically detectable oral changes at any time, with the exception of diminished salivary flow which recovered four to six months later in the case of the parotid glands but not in the submandibular and sublingual glands. The fungal flora changes in these two groups of patients are fully described elsewhere. Both oral and laryngeal groups had similar sharp rises of fungal colony counts with little diminuation even at six months after treatment, despite the abatement of signs and symptoms. It is suggested that direct radiation damage is the primary cause of oral symptoms with the role, if any, of fungi being that of opportunist pathogens on compromised tissues.

Adult↗