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E A Thomas

Publications and source records attributed to E A Thomas.

At least 55 records · Page 3Linked to original sources
PubMed1995

Controlled dietary folate affects folate status in nonpregnant women.

In a study designed to estimate the requirement for dietary folate in nonpregnant women, 17 women (21-27 y) consumed 200, 300, or 400 micrograms/d of total folate for 70 d which was provided by low folate conventional foods (30 micrograms) plus supplemental folic acid. Group means for initial serum and erythrocyte folate and plasma homocysteine concentrations were not significantly different. Serum and erythrocyte folate decreased relative to the initial value in the 200 micrograms/d group (43.4 +/- 12.1%, 13.6 +/- 16.6%, respectively; mean +/- SD), in contrast to an increase in the 400 micrograms/d group (16.8 +/- 52.0%, 10.2 +/- 18.5%, respectively). The final serum folate in the 200 and 300 micrograms/d groups (6.4 +/- 0.8 nmol/L, 7.3 +/- 1.1 nmol/L, respectively) was significantly lower than that of the 400 micrograms/d group (14.3 +/- 2.0 nmol/L), with evidence in the 200 micrograms/d and 300 micrograms/d groups of low ( < 6.8 nmol/L) serum folate concentrations. Differences in final erythrocyte folate did not reach statistical significance, although low values ( < 362 nmol/L) were frequent in subjects with 200 micrograms/d intake. In the 200 micrograms/d group, plasma homocysteine was negatively correlated with serum and erythrocyte folate, and final mean plasma homocysteine (12.6 +/- 1.7 mumol/L) was significantly higher than that of the 300 or 400 micrograms/d groups. Elevated plasma homocysteine levels ( > 16 mumol/L) were observed in the 200 micrograms/d group only.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Case report: radiological appearances in peliosis hepatis.

Peliosis hepatis is an unusual disorder characterized by blood filled hepatic spaces. We describe the appearances of this entity on ultrasonography, computed tomography and magnetic resonance imaging. The importance of peliosis hepatis is that it may be an indicator of a treatable underlying condition.

Female↗
PubMed1994

Pertussis toxin blocks M2 muscarinic receptor-mediated effects on contraction and cyclic AMP in the guinea pig ileum, but not M3-mediated contractions and phosphoinositide hydrolysis.

The effects of pertussis toxin on muscarinic receptor-induced contractions of the isolated guinea pig ileum were investigated. In control tissues, isoproterenol (1 microM) only slightly inhibited contractions in response to oxotremorine-M; however, in pertussis toxin-treated tissues, isoproterenol exhibited an enhanced inhibition of the concentration-effect curve. Under basal conditions, pertussis toxin had no dampening effect on oxotremorine-M-induced contractions. When ilea were precontracted with histamine (1 microM) and then relaxed back to base line using forskolin (10 microM) before contractile responses to oxotremorine-M were measured, pertussis toxin shifted the concentration-effect curve to oxotremorine-M by a 6.1-fold increase in the EC50 value. Ilea were then incubated with [N-(2-chloroethyl)-4-piperidinyl diphenylacetate] (40 nM; 1 hr) in the presence of [[2-[(diethylamino)methyl]-1-piperidinyl]acetyl]-5,11- dihydro-6H-pyrido[2,3b][1,4]benzodiazepine-6-one (1 microM) to selectively inactivate the M3 muscarinic receptors. Under these conditions, pertussis toxin blocked the concentration-effect curve to oxotremorine-M by a 30-fold increase in the EC50 value. Prior treatment of guinea pigs in vivo with pertussis toxin diminished the labeling of a 41-kDa protein in membranes suspensions of the longitudinal muscle incubated with [32P]nicotinamide adenine dinucleotide] and pertussis toxin. This ADP-ribosylation caused a functional uncoupling of the G protein from its receptor as indicated by radioligand-binding studies and second messenger assays. Our results verify that the M2 muscarinic acetylcholine receptor, like the M3 receptor, can elicit contractions of the guinea pig ileum and that the mechanism of this action involves inhibition of adenylate cyclase.

Adenosine Diphosphate Ribose↗
PubMed1993

Physician sets diabetes education as top priority.

Rachmel Cherner, MD, FACP, is an endocrinologist in private practice in Jenkintown, an active member of the Philadelphia County Medical Society, and a delegate to the State Society's House. He writes for Consultant magazine and serves on the staff of North Penn Hospital, and his work as a physician-educator was described in a Medical Economics publication called "Patient Satisfaction." In 1987, he established the Pavilion Diabetes Treatment Center.

Adolescent↗
PubMed1993

Kinetics of activation and in vivo muscarinic receptor binding of N-(2-bromoethyl)-4-piperidinyl diphenylacetate: an analog of 4-DAMP mustard.

4-DAMP mustard (N-2-chloroethyl)-4-piperidinyl diphenylacetate) has been shown to selectively and irreversibly inhibit muscarinic receptors. In an attempt to increase the rate of formation and peak concentration of the reactive intermediate, an analog [N-(2-bromoethyl)-4-piperidinyl diphenylacetate (4-DAMP bromo mustard)] was synthesized and the molecular formula confirmed by mass analysis. The 4-DAMP bromo mustard was shown to cyclize in phosphate buffer (pH 7.4) to the corresponding aziridinium ion with a first-order rate constant (k1) of 0.071 min-1 at 0 degrees C. At 25 degrees C and 37 degrees C, the formation of the aziridinium ion was nearly instantaneous (100% cyclized within 15 sec) at neutral pH. The rate constants (k2) for the hydrolysis of the aziridinium ion at 25 degrees C and 37 degrees C (pH 7.4) were 0.0027 and 0.010 min-1, respectively, in excellent agreement with the published rate constants for the hydrolysis of the aziridinium ion formed from 4-DAMP mustard. In vivo treatment with 4-DAMP bromo mustard in rats resulted in irreversible inhibition of muscarinic receptor binding in peripheral, but not central nervous system, tissues, suggesting that the quickly formed aziridinium ion does not penetrate the blood-brain barrier.

Animals↗
PubMed1993

Functional role for the M2 muscarinic receptor in smooth muscle of guinea pig ileum.

A functional role for the M2 muscarinic receptor in smooth muscle contraction was investigated in isolated guinea pig ileum. Contractile responses to the muscarinic agonist oxotremorine-M (oxo-M) were measured in isolated ilea that had been pretreated with histamine (0.32 microM) and isoproterenol (0.64 microM) to achieve conditions of elevated cAMP. The resulting concentration-effect curve was biphasic, consisting of high (0-50 nM) and low (> 50 nM) potency components. The reversible M2-selective antagonist AF-DX 116 ([[2-[(diethylamino)methyl]-1-piperidinyl]acetyl]-5,11- dihydro-6H-pyrido[2,3b][1,4]benzodiazepine-6-one) (1 and 10 microM) shifted this curve in a manner that was inconsistent with competitive antagonism at a single receptor site; the high affinity component was significantly blocked, whereas there was little effect on the low affinity portion of the curve. To inactivate the M3 muscarinic receptors selectively, ilea were incubated with the irreversible M1/M3-selective muscarinic antagonist 4-DAMP mustard [N-(2-chloroethyl)-4-piperidinyldiphenylacetate] (40 nM) for 1 hr in the presence of AF-DX 116 (1 microM) and were then washed extensively. Under these conditions, the contractile responses to oxo-M, in the presence of histamine and isoproterenol or forskolin, were antagonized by AF-DX 116 (1 microM) in a manner consistent with that mediated by an M2 receptor. AF-DX 116 caused 6.6- and 11-fold increases in the EC50 value for oxo-M for ilea pretreated with isoproterenol and forskolin, respectively, and a significant increase in the Hill coefficient in both cases. Under basal conditions, AF-DX 116 caused only a 1.34-fold increase in the EC50 value and no change in the Hill coefficient. In addition, under basal conditions 4-DAMP mustard treatment shifted the oxo-M contractile response curve to the right approximately 20-fold. However, when histamine was present in combination with isoproterenol or forskolin 4-DAMP mustard treatment shifted the concentration-effect curves for oxo-M to the right only about 3.5-fold. Oxo-M produced an M3-mediated stimulation of phosphoinositide hydrolysis in the longitudinal muscle of rat ileum with an EC50 value of 30 microM. 4-DAMP mustard (10 nM; 1 hr) prevented this response, resulting in a 6.6-fold increase in the EC50 value with a 65% reduction of the maximal response. In contrast, this treatment blocked M2-mediated inhibition of isoproterenol-stimulated adenylate cyclase with only a 2-fold increase in EC50, without affecting maximum inhibition.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Erythrocyte metallothionein response to dietary zinc in humans.

The response of erythrocyte metallothionein to dietary zinc in human subjects was evaluated in a controlled metabolic protocol including standard indices of zinc status. Fifteen male subjects, age 27 +/- 3.6 y, participated in a 90-d, four-phase study consisting of acclimation (7 d; 15 mg Zn/d), treatment (6 wk; either 3.2, 7.2 or 15.2 mg Zn/d), depletion (12 d; 0.55 mg Zn/d) and supplementation (30 d; self-selected diet plus 50 mg Zn/d) phases. During the treatment phase erythrocyte metallothionein decreased in the group fed 3.2 mg Zn/d. Erythrocyte metallothionein decreased during the depletion phase (46 +/- 10%) to below the normal concentration in all groups and increased in the supplementation phase. Plasma zinc concentration decreased in the group fed 3.2 mg Zn/d during the treatment phase relative to the acclimation phase. Erythrocyte zinc decreased in all groups during the depletion phase relative to the treatment phase, and then increased during the supplementation phase. These data suggest that erythrocyte metallothionein can be used as a measure of status in severe zinc depletion and that comparing the change in erythrocyte metallothionein over a 6-wk period can differentiate between low and adequate levels of dietary zinc intake.

Adult↗
PubMed1992

Conversion of N-(2-chloroethyl)-4-piperidinyl diphenylacetate (4-DAMP mustard) to an aziridinium ion and its interaction with muscarinic receptors in various tissues.

A 2-chloroethylamine derivative [N-(2-chloroethyl)-4-piperidinyl diphenylacetate (4-DAMP mustard)] of the selective muscarinic antagonist N,N-dimethyl-4-piperidinyl diphenylacetate (4-DAMP) was synthesized, and its conversion to an aziridinium ion and interaction with muscarinic receptors was investigated. When dissolved in aqueous solution at pH 7.4 and 37 degrees, 4-DAMP mustard released an equivalent amount of chloride. The release of chloride was consistent with a first-order process having a half-time of 5.7 min. The aziridinium ion reached a peak concentration at 32 min, corresponding to 75% of the initial concentration of 4-DAMP mustard. When homogenates of rat brain, heart, and submaxillary gland were incubated with 4-DAMP mustard (9 nM) for 1 hr, washed extensively, and then assayed for muscarinic receptor binding properties, a 56% decrease in the binding capacity of N-[3H]methylscopolamine in the heart and brain and a 71% decrease in the gland were observed, without a significant change in the dissociation constants. The affinity of 4-DAMP mustard and its transformation products for muscarinic receptors was determined in competitive binding experiments with N-[3H] methylscopolamine, and the results show that the aziridinium ion of 4-DAMP mustard was the most potent form, compared with the parent 2-chloroethylamine (4-DAMP mustard) and the alcoholic hydrolysis product. The rates of receptor alkylation by 4-DAMP mustard were measured in the rat heart and gland. Virtually no alkylation (less than 1%) occurred in the heart at a 4-DAMP mustard concentration of 1.6 nM, after 30 min, whereas almost 50% alkylation was observed in the gland under the same conditions. Almost complete alkylation of receptors in the gland could be achieved at a 4-DAMP mustard concentration of 200 nM, after 1 hr. Treatment of the isolated rat ileum with 4-DAMP mustard caused an irreversible blockade of contractions elicited by the muscarinic agonist oxotremorine-M, and this blockade persisted after extensive washing. The results presented here show that 4-DAMP mustard forms an aziridinium ion that binds irreversibly to muscarinic receptors and exhibits selectivity for M3, compared with M2 muscarinic receptors.

Alkylation↗
PubMed1991

The role of ultrasound in the early diagnosis and management of heterotopic bone formation.

Heterotopic bone formation (HBF) is one of the many causes of painful limb swelling and is well recognized as posing clinical, radiological, and pathological diagnostic difficulties. We have evaluated the use of sonography to determine its role in reaching a diagnosis at a time when symptoms are maximal and the radiological diagnostic features absent. Serial ultrasound examination identified unique 'zone phenomea' in a heterogeneous group of eight patients before the classic radiological features appeared. The zone transformation matches the evolution and maturation process described pathologically and forms the basis of an early definitive diagnosis in all cases. The sonographic features are specific for the condition, unlike the scintigraphic appearances. Although CT confirms the peripheral location of the calcification, the low cost, safety, and general availability of ultrasound scanning make it the optimum imaging method for diagnosing and monitoring heterotopic bone formation.

Adult↗
PubMed1990

Duplex ultrasound of the abdominal aorta--a neglected tool in aortic dissection.

The use of duplex ultrasound for the diagnosis and assessment of abdominal aortic dissection and visceral arterial involvement is discussed. Ultrasound is simple and non-invasive and may be superior to aortography in diagnosis; it should be performed after ultrasound assessment of the aortic root. It also provides an effective means of follow-up evaluation if conservative treatment is employed. Three cases are discussed in whom there was no operative intervention. In one case, aortography failed to make a positive diagnosis of aortic dissection. The diagnosis was made by ultrasound in all three cases, one of whom was found subsequently to have Marfan's syndrome.

Adult↗
PubMed1989

Nucleoid halo expansion indirectly measures DNA damage in single cells.

A simple test has been developed that measures how much DNA damage has occurred in a single mammalian cell. The procedure is based on the microscopic examination of "halos" of nucleoids that adhere to coverslips. Nucleoids are produced by flowing salt solutions containing detergents over the attached cells. The nucleoid halos are thought to be a tangle of loops of free DNA that emanate from the remnants of the nucleus. When visualized by staining with ethidium bromide the nucleoid halos first expand, and then contract as the concentration of ethidium increases. Exposure of nucleoids to very low levels of DNA chain-breaking treatments results in the incremental expansion of the halos to a maximum of 15 microns or more. Our assay is based upon quantitating the degree of halo expansion. If intact cells are exposed to DNA-damaging treatments, then allowed increasing periods of post-treatment growth before forming nucleoids, the DNA repair processes result first in expanded and then in contracted halos. By admixing a supercoiled plasma DNA of known length (38 kb) to nucleoids with contracted halos, the fractional halo expansion and the fraction of surviving plasmid supercoils can be measured from the same solution. Use of photodynamic DNA damage showed that the halo expansion was 11.6 times more sensitive than plasmid relaxation. Use of gamma-irradiation showed that the halo expansion was 3.6 times more sensitive than plasmid relaxation. The latter value demonstrates that one break per 137,000 bp results in the expansion of the halos to 63% of their maximal value. We estimate that this method will detect about 5000 breaks per nucleus containing 5 x 10(9) bp.

Animals↗