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R Coleman

Publications and source records attributed to R Coleman.

At least 253 records · Page 14Linked to original sources
PubMed1989

Bayesian regression analysis of non-steady-state phenytoin concentrations: evaluation of predictive performance.

Michaelis-Menten saturable pharmacokinetics confound the determination of appropriate phenytoin maintenance doses. This study retrospectively evaluated the performance of an IBM-PC/XT computer program applying Bayesian regression to the "explicit solution to the Michaelis-Menten equation." Zero to five non-steady-state phenytoin serum concentrations were used to predict either non-steady-state concentrations at least 10 days in the future (n = 49) or steady-state concentrations (n = 20). Non-steady-state concentration prediction precision (% mean absolute error) using 0-5 non-steady-state feedbacks was 137%, 62%, 39%, 31%, 25%, and 15%, respectively, and steady-state concentration prediction precision was 446%, 47%, 50%, 44%, 21%, and 13%, respectively. Elimination of subjects receiving concurrent drugs known to induce phenytoin metabolism significantly improved predictions based on population priors; however, performance improvements were not apparent after two serum level feedbacks. The program provided clinically acceptable predictions with four or more feedbacks. Refinement of population parameters and optimal sampling times should further improve performance.

Aged↗
PubMed1989

Bone secondaries in breast cancer: the solitary metastasis.

The bone scan findings of 160 consecutive cases of breast cancer metastatic to bone presenting to Guy's Hospital between 1982-1987 were retrospectively assessed for number and distribution of lesions. Twenty-one percent of patients relapsed with a solitary bone metastasis. The spine was the commonest site for both solitary (52% of cases) and multiple (87%) metastases. Solitary bone metastases are more common than previously thought.

Bone Neoplasms↗
PubMed1988

The calcium ionophore A23187 increases the tight-junctional permeability in rat liver.

The effect of an increase in intracellular Ca2+ concentration on tight-junctional permeability in rat liver was studied by using the calcium ionophore A23187. Infusion of 100 microliters of dimethyl sulphoxide containing various amounts of A23187 over 30 min into isolated perfused livers was followed by a pulse of horseradish peroxidase (HRP) under single-pass conditions. The first biliary HRP peak, a measure of junctional permeability, was increased 4-fold with 100 micrograms of A23187. There were, however, no significant effects on bile flow or on aspartate aminotransferase leakage as compared with the control at this dosage, and thus the increase in junctional permeability was occurring without evidence of appreciable cholestatic or hepatocellular damage. Higher dosages of A23187, however, caused not only an increase in HRP peak height but also changes in bile flow and increases in aminotransferase leakage, indicating more extensive effects at these higher dosages. A second peak of HRP secretion, occurring 20-25 min after the HRP pulse, was also elevated approx. 3.5-fold; this may indicate that pinocytosis and transcellular movement of HRP are also increased under these conditions.

Animals↗
PubMed1988

Ampicillin inhibits the movement of biliary secretory vesicles in rat hepatocytes.

A number of biliary secretory processes are inhibited by administration of ampicillin to isolated perfused rat livers. Reduction in output was observed for phospholipid, cholesterol, the endogenous protein rat serum albumin and the exogenous protein bovine serum albumin, whilst secretin of bile salts was virtually unaffected. All of the affected materials are secreted by processes involving vesicles which are brought to the appropriate pole of the hepatocyte, and the observed inhibitory effects of ampicillin may, therefore, possibly be due to a blockage in the transport of these substances. The effects of ampicillin were much less marked on materials secreted at the sinusoidal pole of the cell.

Ampicillin↗
PubMed1988

Derived amino acid sequence and identification of active site residues of Escherichia coli beta-hydroxydecanoyl thioester dehydrase.

The nucleotide sequence of the fabA gene encoding beta-hydroxydecanoyl thioester dehydrase, a key enzyme of the unsaturated fatty acid synthesis pathway of Escherichia coli, has been determined by the dideoxynucleotide sequencing technique. Most of the sequence was obtained by sequencing intragenic insertions of the transposon, Tn1000, isolated in vivo. A synthetic primer complementary to a portion of the inverted repeat sequences at the ends of the transposon was used to prime DNA synthesis into the flanking fabA sequences. The gene is composed of 516 nucleotides (171 amino acid residues) encoding a protein with a molecular weight of 18,800. Approximately half of the derived amino acid sequence was confirmed by automated Edman sequencing of peptides obtained by cyanogen bromide cleavage. The active site histidine residue (His-70) has been identified by analysis of the peptides labeled by reaction with 14C-labeled 3-decynoyl-N-acetylcysteamine, a specific mechanism-activated inhibitor. A cysteine residue (Cys-69) adjacent to the active site histidine may play the role in catalysis previously assigned to a tyrosine residue. We also report a simplified purification process for the dehydrase beginning with extracts of a brain which greatly overproduces the enzyme.

Amino Acid Sequence↗
PubMed1988

Sodium valproate inhibits the movement of secretory vesicles in rat hepatocytes.

Sodium valproate (VPA), a simple 8-carbon branched chain fatty acid, is an effective anti-epileptic drug with an occasional serious side effect of liver damage, including the accumulation of triacylglycerols within hepatocytes, and reductions in serum protein concentrations. By investigating the effects of VPA, using biliary fistula rats and isolated perfused rat livers, we have shown that secretion of triacylglycerols and rat serum albumin at the sinusoidal pole of hepatocytes, and of phospholipids, lysosomal contents, and IgA at their biliary pole, are all reduced, to somewhat different extents, by acute VPA administration. In addition, the vesicular transcytosis of exogenous protein (i.e. bovine serum albumin) from the perfusion fluid into bile is also decreased by VPA administration. To determine whether the phenomena were specific to VPA, a control series of experiments was also performed using octanoate (a straight-chain analogue of VPA). With the biliary fistula rats, octanoate did not show inhibition of secretion as compared with the saline controls; with the isolated perfused livers, however, octanoate did show such an inhibition. These phenomena suggest that VPA inhibition of secretion may be a factor in its hepatotoxicity, as the effects are apparent in both the whole animal and the isolated perfused liver, whereas octanoate is not hepatotoxic in the whole animal. Since when octanoate is administered to the isolated liver it causes an inhibition in secretion similar to that caused by VPA, it may be that the large dose of this compound reaching the liver affects a key step in liver metabolism or vesicle transport under these circumstances. Since octanoate does not normally reach the liver in such amounts, as it will normally be metabolized by other tissues, it is not hepatotoxic in the whole animal as is VPA.

Acid Phosphatase↗
PubMed1988

Age and exercise-related changes in myocardial mitochondria in mice.

A quantitative histochemical and an ultrastructural study was performed on the left ventricular myocardium of C57BL/6J female mice to evaluate the effects of aging and running exercise on mitochondrial structure and SDH activity. A comparison was made between 6-month-old ("young") and 27-month-old ("old") sedentary mice with age-matched mice subjected to running schedules (10 or 30 min/d) for 6 weeks. In longer-term studies, 27-month-old mice were given similar daily running schedules over a 10 month period ("long term runners"). No significant differences were found in SDH activity during the normal course of aging in mice (6 to 27 months of age), however, the response to running differed markedly in young versus old mice. "Young" trained mice showed significant increase in SDH activity compared with age-matched sedentary mice, whereas "old" trained mice showed significantly reduced SDH activity. Electron microscopy showed ultrastructural changes in mitochondria associated with aging including the development of large aggregations of mitochondria in subsarcolemmal and paranuclear sites. Running schedules, especially in aged runners, caused an increase in interfibrillar mitochondria hypertrophy, loss of matrix and cristae, incorporation of lipid inclusions and the formation of giant mitochondria. These abnormal mitochondrial changes are interpreted as being degenerative and possibly contributing to the reduced SDH levels found in cardiac myocytes of aged runners. Our results indicate that whereas regular exercise in young animals enhanced SDH activity, in aged mice it may be detrimental rather than beneficial.

Aging↗
PubMed1987

Biliary lipid secretion and its control. Effect of taurodehydrocholate.

Multiple short pulses of taurocholate (TC) brought about, in isolated perfused rat livers, the secretion of phospholipid and cholesterol into bile; the lipids showed an appreciable lag period behind the bile-salt secretion, and there was considerable variability in response, both between low and high dose pulses of TC and, at the higher dose, even between individual livers. When a background continuous infusion of taurodehydrocholate (a hydrophilic non-micelle-forming bile-salt analogue) was superimposed upon the short TC pulses, the lipid secretion showed much better control, and the lipid peaks were of more uniform size, following more closely, or more coincident with, the bile-salt output peaks. Taurodehydrocholate may provide a signal for the control of the supply and delivery of lipid vesicles to the bile-canalicular membrane, from where the lipid vesicles are then removed by the action of the pulses of TC.

Animals↗
PubMed1987

Output of lysosomal contents and cholesterol into bile can be stimulated by taurodehydrocholate.

Although biliary secretion of phospholipids and cholesterol is principally dependent on bile-salt secretion, at low bile-salt output secretion of some lipids continues; also the amount of cholesterol secretion is more than that of phospholipid under these conditions, but the origin of this cholesterol is not known. Taurodehydrocholate was continuously infused in isolated perfused rat livers under recycling perfusion conditions and the biliary lysosomal output and lipid output measured. The rate of acid phosphatase and beta-glucuronidase output increased 30-60 and 60-90 min respectively after liver isolation under these conditions. The rate of output of cholesterol and phospholipid increased in all the samples collected from taurodehydrocholate-infused livers. The increase in cholesterol output was approximately twice that of phospholipid output, leading to an increase in the cholesterol/phospholipid ratio in the bile.

Animals↗
PubMed1987

Endocytosis of native and cationized ferritin by intralobular duct cells of the rat parotid gland.

The ability of the intralobular ducts of the rat parotid gland to take up protein from the lumen was examined after retrograde infusion of native and cationized ferritin. At high concentrations (3-10 mg/ml), cells of both intercalated- and striated ducts avidly internalized the tracers. No differences were noted in the mode of uptake or fate of native or cationized ferritin. Large, apical ferritin-containing vacuoles up to 5 microns in size were present in cells of the intercalated ducts after infusion for 15 min. Small, smooth-surfaced spherical or flattened vesicles and tubules containing ferritin were also observed, often in association with the large vacuoles. Ferritin uptake increased with increasing infusion time, up to 1 h. Uptake by the striated ducts was less consistent than by the intercalated ducts, and occurred mainly in small vesicles and tubules. Secondary lysosomes became labeled with ferritin in both cell types. Ferritin was not observed in the Golgi saccules, nor was it discharged from the cells at the basolateral surfaces. At low concentrations (0.3-1 mg/ml), uptake was reduced, especially by cells of intercalated ducts, and differences were noted in the behavior of the two tracers. Cationized ferritin was internalized mainly into vesicles and tubules of cells of striated ducts; little uptake of native ferritin occurred at low concentrations. These results demonstrate that the ductal cells of the salivary glands are capable of luminal endocytosis of foreign proteins. They also suggest that in addition to modifying the primary saliva by electrolyte reabsorption and secretion, and secretion of various glycoproteins, the ductal cells are able to reabsorb proteins secreted by the acinar cells.

Animals↗
PubMed1987

A novel whole blood capillary technic for measuring the prothrombin time.

The prothrombin time (PT) is frequently performed to monitor anticoagulant therapy. Although relatively simple to perform, it requires venipuncture and laboratory resources for sample handling and analysis. A recently developed capillary whole blood device that uses fingerstick samples was evaluated. Paired capillary whole blood and reference plasma PTs were performed in 858 samples from 732 subjects. The PT for normal volunteers (n = 193) was 11.8 +/- 0.9 seconds with the use of the new instrument and 12.1 +/- 0.5 seconds with the use of the reference method. In samples from 539 patients receiving anticoagulants, the correlation coefficient between the two methods was 0.96. Venous whole blood without anticoagulant and capillary whole blood gave equivalent results, which suggests that the fingersticks do not effect the quality of the specimen. Variation in hematocrit between 23.4% (0.34) and 53.8% (0.538) did not alter the performance of the instrument. The new instrument is easy to use and may allow testing by nonlaboratory personnel and patients. It obviates the need for venipuncture, provides immediate results, and appears to be comparable in accuracy to current reference methods.

Anticoagulants↗