Treatment of Rat Liver Microsomes with Phospholipase C: Effect on Phospholipids and on Cytochromes P450 and b5

Treatment of rat liver microsomes with phospholipase C (CL weLchii) revealed the following: 1. The polar headgroups of 70°/o of the phospholipids can be removed by treatment of microsomes with phospholipase C. When phospholipids that have been extracted from microsomes are treated with phospholipase C, 900/o can be hydrolyzed, suggesting that certain phospholipids are protected from the enzyme in situ. 2. Neither the native conformations of cytochromes P450 and b5 nor their binding to the microsomal membrane are directly affected by phospholipase C treatment. 3. The diglycerides resulting from the action of phospholipase C can be hydrolyzed by an enzyme in the microsomal membrane to yield free fatty acids which partially denature cytochrome P450. 4. The pattern of this partial denaturation is a further indication of the existence of a number of cytochrome P450 species in the microsomal membrane

Differential Effects of Rotenone and Amytal on Mitochondrial Electron and Energy Transfer

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Succinate-linked Acetoacetate Reduction: II. ELECTRON TRANSFER PATHWAY AND ENERGY REQUIREMENT

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Thyroid Control over Biomembranes

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65831/1/j.1432-1033.1980.tb04795.x.pd

Treatment of Rat Liver Microsomes with Phospholipase C: Effect on Phospholipids and on Cytochromes P450 and b5

Treatment of rat liver microsomes with phospholipase C (CL weLchii) revealed the following: 1. The polar headgroups of 70°/o of the phospholipids can be removed by treatment of microsomes with phospholipase C. When phospholipids that have been extracted from microsomes are treated with phospholipase C, 900/o can be hydrolyzed, suggesting that certain phospholipids are protected from the enzyme in situ. 2. Neither the native conformations of cytochromes P450 and b5 nor their binding to the microsomal membrane are directly affected by phospholipase C treatment. 3. The diglycerides resulting from the action of phospholipase C can be hydrolyzed by an enzyme in the microsomal membrane to yield free fatty acids which partially denature cytochrome P450. 4. The pattern of this partial denaturation is a further indication of the existence of a number of cytochrome P450 species in the microsomal membrane

Overdiagnosis and overtreatment of breast cancer: Estimates of overdiagnosis from two trials of mammographic screening for breast cancer

Randomised controlled trials have shown that the policy of mammographic screening confers a substantial and significant reduction in breast cancer mortality. This has often been accompanied, however, by an increase in breast cancer incidence, particularly during the early years of a screening programme, which has led to concerns about overdiagnosis, that is to say, the diagnosis of disease that, if left undetected and therefore untreated, would not become symptomatic. We used incidence data from two randomised controlled trials of mammographic screening, the Swedish Two-county Trial and the Gothenburg Trial, to establish the timing and magnitude of any excess incidence of invasive disease and ductal carcinoma in situ (DCIS) in the study groups, to ascertain whether the excess incidence of DCIS reported early in a screening trial is balanced by a later deficit in invasive disease and provide explicit estimates of the rate of 'real' and non-progressive 'overdiagnosed' tumours from the study groups of the trials. We used a multistate model for overdiagnosis and used Markov Chain Monte Carlo methods to estimate the parameters. After taking into account the effect of lead time, we estimated that less than 5% of cases diagnosed at prevalence screen and less than 1% of cases diagnosed at incidence screens are being overdiagnosed. Overall, we estimate overdiagnosis to be around 1% of all cases diagnosed in screened populations. These estimates are, however, subject to considerable uncertainty. Our results suggest that overdiagnosis in mammography screening is a minor phenomenon, but further studies with very large numbers are required for more precise estimation

Benefits and risks of menopausal estrogen and/or progestin hormone use,

Current evidence is reviewed here on risks and benefits of estrogen and progestin use by peri- and postmenopausal women in relation to the following conditions: endometrial cancer, breast cancer, osteoporosis, and coronary artery disease (CAD). On balance, estrogen therapy appears to be beneficial for menopausal women, as it probably reduces the risks of CAD and osteoporosis, two of the major causes of mortality and morbidity. Although unopposed estrogen therapy increases the risk of endometrial cancer, that cancer is relatively rare and is not fatal in the vast majority of cases associated with estrogen use. Definitive conclusions about the relation of menopausal estrogens to breast cancer cannot be drawn due to inconsistent evidence to date. Although evidence from randomized controlled trials is lacking, biochemical and clinical evidence suggest that progestin supplementation is associated with a reduction in endometrial cancer risk in women taking menopausal estrogens. Progestin supplementation also may augment the beneficial effects of estrogens in providing protection against osteoporosis, although this effect is not yet well established. There is little direct evidence bearing on the relation of menopausal progestins to breast cancer. Although studies of CAD per se are lacking at present, progestins probably unfavorably alter lipoprotein profiles, thereby increasing a user's risk of CAD. Given the relatively high incidence and mortality of CAD in postmenopausal women, any negative effects on CAD risk could potentially counterbalance beneficial effects on other causes. We conclude that estrogen replacement therapy is of potential benefit to postmenopausal women, but that the question of progestin supplementation requires further study, particularly for CAD risk.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27382/1/0000412.pd