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S Dimmitt

Publications and source records attributed to S Dimmitt.

11 recordsLinked to original sources

Oxidation of low-density lipoproteins: effect of antioxidant content, fatty acid composition and intrinsic phospholipase activity on susceptibility to metal ion-induced oxidation.

The oxidative modification of low-density lipoprotein (LDL) may play an important role in atherogenesis. Our understanding of the mechanism of LDL oxidation and the factors that determine its susceptibility to oxidation is still incomplete. We have isolated LDL from 45 healthy individuals and studied the relationship between LDL fatty acid, vitamin E and beta-carotene composition, intrinsic phospholipase A2-like activity and parameters of LDL oxidation. LDL was exposed to a copper ion-dependent oxidising system and the kinetics of oxidation studied by monitoring formation of fatty acid conjugated dienes. The length of the lag phase of inhibited lipid peroxidation was measured as well as the rate of lipid peroxidation during the propagation phase. There was no significant correlation between LDL antioxidant vitamin or fatty acid composition and lag time to LDL oxidation. Oleic acid was negatively correlated with the rate of LDL oxidation (r = -0.41, P < 0.01) whilst linoleic acid was significantly correlated with the extent of LDL oxidation measured by the production of total dienes (r = 0.34, P < 0.05). Interestingly, LDL vitamin E content was positively correlated with both the rate (r = 0.28, P < 0.05) and extent of LDL oxidation (r = 0.43, P < 0.01). LDL isolated from this group of subjects showed significant intrinsic phospholipase-like activity. The phospholipase activity, whilst not correlated with lag time, was significantly correlated with both rate (r = 0.43, P < 0.01) and total diene production (r = 0.44, P < 0.01) of LDL oxidation. We conclude that antioxidant content, fatty acid composition and intrinsic phospholipase activity have little influence on the lag time of Cu-induced LDL oxidation. These components do however, significantly influence both the rate and extent of LDL oxidation, with increased vitamin E, linoleic acid content and phospholipase activity associated with faster and more extensive oxidation. The possible pro-oxidant effect of vitamin E has interesting implications for the postulated 'protective' effects of vitamin E on atherogenesis.

Antioxidants

Tissue peroxidase in the normal and neoplastic salivary gland.

Peroxidase activity was measured by two colorimetric methods in six neoplastic tumors of the parotid salivary gland. When p-phenylenediamine was used as the hydrogen donor co-substrate, peroxidase activity was absent or reduced from 6 to 22% of normal in these tumors. Cross reactivity with normal peroxidase antibody could not be demonstrated in tumors exhibiting negative activity. Two neoplastic salivary glands had well-described, encapsulated tumors which showed reduced peroxidase activity when compared with the normal uninvolved portion. However, when guaiacol was substituted for p-phenylenediamine, normal activity was recorded. After dialysis, peroxidase activity was not enhanced. Mixing experiments showed no effect of the tumor extract on the peroxidase activity of normal saliva, nor on salivary gland supernatant. Normal salivary gland peroxidase was inhibited 90% by 10(-2) g/L amino-triazole, but neoplastic tumors were inhibited less (13 and 73%). It is suggested that peroxidase is a simple marker for the detection of neoplasia and can be of value in the differentiation of benign tumors.

Adenoma

Decreased amniotic fluid peroxidase in malignancy of the cervix.

Studies of amniotic fluid obtained at various times throughout the last trimester of pregnancy from patients with carcinoma of the cervix indicate a complete deficiency of peroxidase activity. Dialysis partially restores the enzyme activity. Cervical epithelial tumor cells apparently release a dialyzable, low molecular weight inhibitory substance directed specifically toward peroxidase. If this proves to be true in future studies, the peroxidase assay could be a sensitive means of differentiating between carcinoma and dysplasia. A peroxidelike substance was also present in the amniotic fluids obtained from patients with carcinoma. Other investigators have demonstrated large amounts of peroxide in malignant tumors. These elevated peroxide levels might well be directly related to deficient peroxidase activity rather than being a result of other abnormal enzyme levels which have been regarded as being principally involved in the metabolism of this highly toxic molecule.

Amniotic Fluid

The Determination of Peroxidase in Amniotic Fluid.

Analyzing total peroxidase activity in amniotic fluid is extremely simple, requiring only 1 1/2 minutes of incubation at room temperature and a spectrophotometer. Peroxidase, clearly detectable at as early as 17 weeks' gestation in the amniotic fluid, increases 100-fold by term. The increase follows a predictable rising curve and can be used to estimate the fetal age. Maturation of the fetal salivary gland is most probably the source of rising amniotic fluid peroxidase levels. Samples from complicated pregnancies are lower than normal, do not increase as rapidly, and probably can be bracketed into their own ranges for gestational age evaluation.

Amniotic Fluid

Thyroid peroxidase deficiency in Batten-Spielmeyer-Vogt disease.

Thyroid tissue from two patients with Batten-Spielmeyer-Vogt disease (BSV) was studied for peroxidase enzyme activity and for morphological abnormalities by light and electron microscopy. Diagnosis was confirmed by the demonstration of intracytoplasmic material identical to that described in other reported cases of BSV. There was a substantial decrease in peroxidase activity in the thyroid tissue from both patients. An abnormally low level of peroxidase activity had previously been demonstrated in the white blood cells of these patients. Thyroid biopsy offers obvious advantages over brain biopsy, provides adequate tissue for enzyme analysis, and allows the demonstration of the intracytoplasmic structures characteristic of BSV.

Autopsy

Leukocyte peroxidase deficiency in a family with a dominant form of Kuf's disease.

Use of a spectrophotomtetric assay of peroxidase with p-phenylenediamine as cosubstrate demonstrated deficient enzymne activity in leukocytes from two patients with a dominantly inherited form of ceroid lipofuscinosis (Kuf's disease) and a clinically hlealthy unaffected sibling. When the reaction was performned in the absence of added hydrogen peroxide, oxidation of the p-phenylenediamnine cosubstrate (indicating the presence of endogenous peroxide) occurred only with enzyme samnples from the three siblings but not with those from a large number of unrelated, unaffected controls. This demonstrates that the deficiency of peroxide) found previously in the recessively inherited infantile and juvenile formns of ceroid lipofuscinosis (Batten-Spielmeyer-Vogt disease) is also present in an adult form with dominant inheritance.

Adult