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Biomedical subjects

E Sykes

Publications and source records attributed to E Sykes.

At least 19 recordsLinked to original sources

Interactions of Solutol HS 15 and Cremophor EL with plasma lipoproteins.

Two emulsifying agents, Solutol HS15 and Cremophor EL, were compared with regard to their effects on human plasma lipoproteins in vitro and on mouse plasma lipoproteins in vitro and in vivo. Both agents promoted binding of a hydrophobic photosensitizing agent (C8KC) to a circulating plasma species of low bouyant density. Persistence of this material was greater with Cremophor than with Solutol. Experiments carried out with labeled Solutol indicated that the vehicle itself is a component of this new species. High concentrations of either vehicle ( > or = 0.06%) led to decreased electrophoretic mobility of human LDL and HDL in vitro. In the mouse, a different effect was observed, resulting in complex changes in electrophoretic mobility of plasma lipoproteins. The plasma half-life of C8KC in the circulation of the mouse was correlated with the persistence of an altered electrophoretic lipoprotein pattern. Since Solutol and C8KC showed similar half-lives, this result suggests that the plasma half-life of the sensitizer is correlated with the persistence of the vehicle. While Solutol and Cremophor were designed to be vehicles for drug formulation, they also influence persistence of some drugs in the circulation.

Animals↗

Fractionation of Cremophor EL delineates components responsible for plasma lipoprotein alterations and multidrug resistance reversal.

Treatment of cancer patients with 3-h infusions of taxol formulated with Cremophor EL resulted in a marked decrease in the electrophoretic mobility of all plasma lipoproteins. Cremophor was fractionated by reverse-phase chromatography to determine which components were responsible for this behavior. Effects of different Cremophor fractions on reversal of multidrug resistance, amino acid transport, and cytotoxicity also were evaluated using murine leukemia cells in culture. Lipoprotein alterations were caused by Cremophor components of intermediate hydrophobicity, which also antagonized amino acid transport and decreased viability of murine leukemia cells. Cremophor components responsible for reversal of multidrug resistance were of greater hydrophobicity. The lipoprotein-altering components of Cremophor could be selectively removed without affecting either taxol solubilization or multidrug-resistant reversal.

Animals↗

Effects of Cremophor EL on distribution of Taxol to serum lipoproteins.

The clinical formulation of the anti-tumour agent Taxol involves the use of a mixture of ethanol and Cremophor EL. Gel electrophoresis and density-gradient ultracentrifugation were used to detect effects of Taxol infusions on serum lipoproteins. Use of the Cremophor vehicle results in a decrease in the electrophoretic mobility of serum lipoproteins along with the appearance of a lipoprotein dissociation product. These effects persist during a 24 h infusion and for at least 1.5 h afterwards, and can be reproduced in vitro using purified high-density lipoprotein (HDL) or low-density lipoprotein (LDL). In control serum, Taxol binds to albumin > HDL, but after serum is exposed to Cremophor EL in vitro or in vivo substantial binding of Taxol to the lipoprotein dissociation product(s) was observed. The latter could represent an important factor in taxol biodistribution.

Centrifugation, Density Gradient↗

Comparison of the HemoCue beta-glucose photometer and reflotron for open heart surgery.

The HemoCue beta-glucose photometer (Angelholm, Sweden) was evaluated for use in monitoring blood glucose in both diabetic and nondiabetic patients undergoing open heart surgery. Because occasional discrepancies were noted in patients with low total proteins when the Reflotron (Boehringer Mannheim, Indianapolis, IN) was used for this purpose, the effects of protein and hematocrit on glucose results from both instruments were investigated and compared with plasma values from a Paramax 720 ZX (Baxter Healthcare, Irvine, CA). Linear-regression analysis of the HemoCue results (y) versus Paramax (x) yielded y = 0.956x + 0.35, r2 = 0.980, with Sy/x = 0.57 mmol/L (10.3 mg/dL). Results from the Reflotron (y) versus Paramax (x) yielded y = 1.075x - 0.10, r2 = 0.964, with Sy/x = 0.99 mmol/L (17.8 mg/dL). Bias plots of (HemoCue-Paramax) or (Reflotron-Paramax) versus glucose, hematocrit, or protein showed no effect of glucose on the results from either instrument and no effect of protein or hematocrit on the HemoCue findings. The Reflotron, however, showed a positive bias of up to 3.5 mmol/L (63 mg/dL) at protein concentrations between 30-40 g/L (3.0-4.0 g/dL) and a possible positive bias at low hematocrit levels.

Blood Chemical Analysis↗

Laboratory measurement of bilirubin.

Several methods for determination of total bilirubin and its fractions have been critically discussed. Methods for serum determinations are summarized in Table 1. Because results of direct bilirubin cannot necessarily be equated with conjugated bilirubin, care must be taken in interpreting results from different laboratories, and clinicians are encouraged to become familiar with methods in use at their own institutions. Despite problems reported in the literature, bilirubin determinations, together with a reference range established for one's own patient population, should provide valuable information for patient management.

Amniotic Fluid↗

Metastatic sweat gland carcinoma: response to 5-fluorouracil infusion.

A 78-year-old white male presented with metastatic sweat gland carcinoma involving regional lymph nodes, pleura, pericardium, and chest wall. A complete response of three months duration was achieved by using a 96-hour infusion of 5-fluorouracil. This is the first report of a complete response to systemic chemotherapy in metastatic sweat gland carcinoma.

Aged↗

Effect of S-adenosylhomocysteine on insulin-independent release of pyruvate dehydrogenase activator from rat adipocyte plasma membranes.

The addition of insulin to adipocyte plasma membranes has been shown to release a low molecular weight, acid stable mediator which activates mitochondrial pyruvate dehydrogenase. The insulin-dependent release of this activator is dependent on the method used to prepare the plasma membranes. Adipocyte plasma membranes prepared in 0.25 M sucrose, 10 mM MOPS, pH 7.4 released an activator of pyruvate dehydrogenase in an insulin-independent manner. Insulin is required to stimulate phospholipid methylation in these membranes. The inhibition of insulin-stimulated phospholipid methylation with 1 mM S-adenosylhomocysteine resulted in a significant increase in amount and/or activity of the pyruvate dehydrogenase activator. The insulin-dependent dependent release of mediators of insulin action from adipocyte plasma may be regulated by phospholipid methylation.

Adipose Tissue↗

Association of high-molecular-mass and electrophoretically atypical alkaline phosphatases.

Polyacrylamide gel electrophoresis of alkaline phosphatase may yield abnormally migrating fractions; these include high-molecular-mass alkaline phosphatase, which remains at the gel origin, and immunoglobulin-alkaline phosphatase complexes, which have a mobility approximately 1/3 that of liver isoenzyme. We performed a retrospective study of 19 patients whose sera exhibited atypical alkaline phosphatase fractions, defined as bands whose mobility was slower than bone, liver, or intestinal alkaline phosphatase; 17 had a mobility approximately 1/3 that of liver isoenzyme and 16 also exhibited gel origin enzyme activity or high-molecular-mass bands. The strong association of the atypical and high-molecular-mass alkaline phosphatases suggests that they may be structurally related, both consisting of either immunoglobulin-enzyme complexes or membrane-alkaline phosphatase complexes. This hypothesis is supported by (1) one serum available for investigation containing alkaline phosphatase-immunoglobulin complexes in both abnormally migrating fractions, but on detergent treatment showing no evidence of membrane-bound enzyme; (2) detergent treatment of serum from patients with only high-molecular-mass alkaline phosphatase creating bands with a mobility of approximately 1/3 that of the liver isoenzyme.

Adolescent↗

Effect of phospholipase C on high-molecular-mass alkaline phosphatase in serum.

Electrophoresis of some serum samples on polyacrylamide gel, followed by staining for alkaline phosphatase (EC 3.1.3.1), produces a band of activity at the gel origin. This high-Mr band consists of liver membrane fragments containing alkaline phosphatase and other enzymes. Alkaline phosphatase is closely associated with phosphatidylinositol in liver plasma membranes, and we have found that phospholipase C (EC 3.1.4.3) from Bacillus cereus, known to possess some phosphatidylinositol specificity, was able to release liver alkaline phosphatase from the high-Mr band. Two preparations of phospholipase C from Clostridium perfringens, however, which has no phosphatidylinositol specificity, had no effect on the alkaline phosphatase activity in the high-Mr band.

Adult↗

Glycosyltransferase levels in tumors metastatic to liver and in uninvolved liver tissue.

Elevated levels of three plasma glycosyltransferases were associated with neoplasia in cancer patients, notably those with tumor metastatic to liver. We examined levels of sialyltransferase, galactosyltransferase, and fucosyltransferase in metastatic tumor and apparently uninvolved host liver tissue in attempts to delineate possible sources of elevated plasma enzyme levels. Highest levels of fucosyltransferase activity were found associated with tumor tissue; in contrast, sialyltransferase and galactosyltransferase activity was often highest at the tumor-liver interface.

Female↗