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S Eaton

Publications and source records attributed to S Eaton.

At least 19 recordsLinked to original sources
PubMed1992

The Drosophila hedgehog gene is expressed specifically in posterior compartment cells and is a target of engrailed regulation.

cDNAs were isolated that represent transcripts of the Drosophila segment polarity gene, hedgehog (hh). Sequence analysis reveals a motif characteristic of a transmembrane domain, suggesting that the hh protein is membrane-associated. hh expression in epidermal cells is confined to the posterior compartments and coincides precisely with that of engrailed (en). Despite the similar patterns of expression in the cellular blastoderm, hh expression is independent of en, but hh expression becomes sensitive to and dependent on en during the extended germ band stage. The ectopic expression of hh that is normally induced in patched (ptc) mutant embryos does not appear in ptc en double mutants. We discuss these findings in terms of the relationship between en and hh, and the role of the hh function.

Amino Acid Sequence↗
PubMed1992

Pharmacokinetic behavior of gadoteridol injection.

RATIONALE AND OBJECTIVES: To assess the safety and pharmacokinetics of gadoteridol injection (0.5 M) in 18 healthy male volunteers in a phase I clinical trial. METHODS: Volunteers were assigned to one of six dosing groups: 0.05, 0.1, 0.15, 0.2, 0.25, and 0.3 mmol/kg gadoteridol (0.5 M), in an ascending dose study. Physical examination, vital signs, electrocardiogram, clinical laboratory tests, and serum and urine samples were obtained at selected time points before and after administration of gadoteridol. RESULTS AND CONCLUSIONS: No significant changes in vital signs, physical examination, clinical laboratory values, or electrocardiogram, that were believed by the principal investigator to be related to the administration of the contrast agent, were observed. A single adverse event (transient hive) believed to be related to contrast agent administration was observed in one volunteer. Pharmacokinetic data show that the elimination half-life and the distribution half-life were independent of the dose used. The mean distribution half-life was 0.20 +/- 0.04 hours, the mean elimination half-life was 1.57 +/- 0.08 hours, and greater than 94% of the drug was excreted in the urine in 24 hours.

Adolescent↗
PubMed1991

Quantitation of acyl-CoA and acylcarnitine esters accumulated during abnormal mitochondrial fatty acid oxidation.

We have used radio-high pressure liquid chromatography to study the acyl-CoA ester intermediates and the acylcarnitines formed during mitochondrial fatty acid oxidation. During oxidation of [U-14C]hexadecanoate by normal human fibroblast mitochondria, only the saturated acyl-CoA and acylcarnitine esters can be detected, supporting the concept that the acyl-CoA dehydrogenase step is rate-limiting in mitochondrial beta-oxidation. Incubations of fibroblast mitochondria from patients with defects of beta-oxidation show an entirely different profile of intermediates. Mitochondria from patients with defects in electron transfer flavoprotein and electron transfer flavoprotein:ubiquinone oxido-reductase are associated with slow flux through beta-oxidation and accumulation of long chain acyl-CoA and acylcarnitine esters. Increased amounts of saturated medium chain acyl-CoA and acylcarnitine esters are detected in the incubations of mitochondria with medium chain acyl-CoA dehydrogenase deficiency, whereas long chain 3-hydroxyacyl-CoA dehydrogenase deficiency is associated with accumulation of long chain 3-hydroxyacyl- and 2-enoyl-CoA and carnitine esters. These studies show that the control strength at the site of the defective enzyme has increased. Radio-high pressure liquid chromatography analysis of intermediates of mitochondrial fatty acid oxidation is an important new technique to study the control, organization and defects of the enzymes of beta-oxidation.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1991

Novel protein-DNA interactions associated with increased immunoglobulin transcription in response to antigen plus interleukin-5.

Although much has been learned about basal levels of immunoglobulin (Ig) transcription, the regulatory effects of cytokines and antigen (Ag) upon Ig expression in lymphocytes have not been fully characterized. We previously reported that Ag plus interleukin-5 (IL-5) caused increased steady-state Ig mRNA levels in Ag-specific cell lines. In this study, we have identified a region between -250 and -125 bp 5' of the Ig transcription start site that is necessary for the induction of increased mu mRNA levels by Ag plus IL-5. Mobility shift and UV cross-linking studies indicated that IL-5 plus Ag induced increased protein binding to this region. Furthermore, this sequence was found to be closely related to another A + T-rich sequence at -525 bp 5' of the transcription start site. Both sequences exhibited similar B-cell-specific and inducible protein binding. Our data suggest that treatment with IL-5 plus Ag induces several DNA-binding proteins, some of which may participate in increasing Ig transcription above basal levels by binding to sequences 5' of the octamer motif.

Animals↗
PubMed1990

Intermediates of peroxisomal beta-oxidation. A study of the fatty acyl-CoA esters which accumulate during peroxisomal beta-oxidation of [U-14C]hexadecanoate.

1. 14C-labelled fatty acyl-CoA esters resulting from beta-oxidation of [U-14C]hexadecanoate by peroxisomal fractions isolated from rats treated with clofibrate showed the presence of the full range of saturated intermediates down to acetyl-CoA. 2. The pattern of intermediates generated was fairly constant. At low concentrations of [U-14C]hexadecanoate (50 microM), decanoyl-CoA was present in lowest amounts. At higher concentrations of [U-14C]hexadecanoate (greater than 100 microM), all intermediates of chain length shorter than 12 carbon atoms (except acetyl-CoA) were present at similar low concentrations; the process of beta-oxidation now resembling chain-shortening of hexadecanoate by two cycles of beta-oxidation. 3. In the absence of an NAD(+)-regenerating system [pyruvate and lactate dehydrogenase (EC 1.1.1.28)] 2-enoyl- and 3-hydroxyacyl-CoA esters were generated, suggesting that re-oxidation of NADH is essential for optimal rates of peroxisomal beta-oxidation in vitro. 4. At high concentrations of [U-14C]hexadecanoate (greater than 100 microM), 3-oxohexadecanoyl-CoA was produced, suggesting that thiolase (acetyl-CoA acetyltransferase; EC 2.3.1.9) can become rate-limiting for peroxisomal beta-oxidation.

Acyl Coenzyme A↗
PubMed1990

Pharmacokinetic analysis of blood distribution of intravenously administered 153Gd-labeled Gd(DTPA)2- and 99mTc(DTPA) in rats.

Rat plasma distribution data obtained following IV administration of 99mTc(DTPA) alone or after co-administration of 99mTc(DTPA) and 153Gd-labeled Gd(DTPA)2- at 0.001, 0.1, and 1.0 mmol Gd/kg were evaluated using compartmental modeling techniques. A three-compartment open model was found to fit the data significantly better (P less than 0.01) than a two- or four-compartment open model. This model incorporates and links the plasma and urine data and includes a delay to account for the transit time through the kidneys/ureters. The two nonplasma compartments of the model were assumed to be related to rapidly and slowly equilibrating tissues. Tc(DTPA) and Gd(DTPA)2- had nearly identical pharmacokinetic profiles in plasma and the rate constants were essentially the same. No significant dose dependent pharmacokinetic differences were found for the range of Gd(DTPA)2- doses tested. Simulations of the proposed three-compartment model were used to generate concentration-time curves for each of the three compartments.

Animals↗
PubMed1990

Assays for plasma complement activation by x-ray contrast media.

Hemolytic complement activity and a C3a radioimmunoassay (RIA) were investigated for their ability to characterize contrast media (CM) with respect to complement activation. The CM tested were commercial formulations of diatrizoate, iodamide, iothalamate, ioxaglate, iohexol, and iopamidol. When plasma was exposed to CM, the hemolytic complement activity decreased and the C3a concentration increased. The C3a assay had a larger dynamic range and therefore more ability to discriminate among the CM. Using C3a data from pooled plasma or from individual donors' plasma, nonionic iopamidol (as Isovue 300) had lower complement-activating potential (P less than .005 and P greater than .05, respectively) than all of the ionic media based on diatrizoate, iothalamate, iodamide, and ioxaglate. The ranges of mean C3a values generated by saline, nonionic CM, and ionic CM were 48 to 60, 65 to 173, and 807 to 3272 ng C3a/50 microL, respectively. Complement activation was found to correlate with osmolality (r = 0.945, all media) and with molarity (r = 0.994, diatrizoates).

Complement Activation↗
PubMed1990

Repression of ci-D in posterior compartments of Drosophila by engrailed.

A Drosophila strain was isolated that carries a lacZ-bearing recombinant P element integrated in the cubitus interruptus Dominant (ci-D) locus. This strain expresses beta-galactosidase in the anterior compartments of embryos and imaginal discs, suggesting that expression of ci-D is anterior-compartment specific. DNA from ci-D was cloned. In situ hybridization to imaginal discs confirmed that ci-D RNA is present only in anterior compartments. ci-D RNA is also limited to the anterior compartments at the germ-band extension stage of embryonic development, although not at earlier stages. In engrailed mutants, ci-D expression was derepressed in the posterior compartments of both embryos and imaginal discs. We postulate that engrailed, which is expressed in only the posterior compartments of embryos and imaginal discs, represses ci-D in these cells.

Animals↗
PubMed1989

Transcriptional regulation of immunoglobulin heavy chain and T-cell receptor beta chain genes.

We have identified factors that bind to functionally important regions in IgH chain promoters and enhancer. One promoter factors is identical to u-EBP-E, an enhancer binding protein. Several promoter-binding proteins are present preferentially in either B cells or fibroblasts although most enhancer-binding proteins have a ubiquitous distribution. Additional characterization of these factors will further our understanding of the mechanisms by which IgH promoters and enhancers interact to achieve B-cell restricted and developmental stage-specific expression of IgH genes. The identification of a TCR beta chain enhancer will allow us to pursue similar questions with respect to the regulated expression this locus.

Animals↗
PubMed1989

Creatine kinase activity in sickle cell disease.

Creatine kinase activity was measured in 28 patients in the steady state of sickle cell disease and ranged from 4-45 IU/l, comparable with that found in healthy adult caucasians. Creatine kinase activity was also measured in 14 patients admitted consecutively for the treatment of vaso-occlusive sickle cell crises. Creatine kinase activity remained within the normal range in eight of these 14 patients throughout their admission; none had muscle pain or a chest syndrome. In the remaining six, three with muscle pain and three with a chest syndrome, increased activity was found on one or more days. A further 17 patients with vaso-occlusive sickle cell crises, associated with muscle pain, were studied. Creatine kinase activity was significantly raised in all 17, the mean creatine kinase activity for men was 578.8 IU/l and 210.6 IU/l for women, with the highest values (up to 1790 IU/l) found in those who had exercised before admission. Measurement of creatine kinase activity may therefore be a useful marker of muscle perturbation due to sickling.

Adolescent↗
PubMed1988

Preliminary pulsatile flow bench validation of a thermodilution right ventricular ejection fraction system.

A preliminary Pulsatile Flow Bench validation of the REF-1 Right Ventricular Ejection Fraction (RVEF) computer and catheter system was performed to determine the accuracy of the current REF-1 system. These results reflect the accuracy of the current REF-1 system and not the final REF-1 system that will be released at a later date. The Pulsatile Flow Bench cardiac output and ejection fraction ranges included in this study are 1 to 6 Lpm and 15% to 60%, respectively. Currently, plans are being made to increase the flow bench cardiac output range to 10 Lpm with ejection fractions up to 70%. The results of this study show a correlation coefficient of 0.94 (adjusted R-square) between flow bench ejection fractions and REF-1 system ejection fractions. Also, the correlation coefficient between flow bench cardiac output and REF-1 system cardiac output was determined to be 0.99 (adjusted R-square).

Calibration↗
PubMed1988

Water quality control trials: statistical tables for direct comparison between membrane filtration bacterial counts and the multiple tube method with a description of the bacteriological method.

Experiments in the quality control of water samples are being conducted in the Public Health Laboratory Service and the water industry in the United Kingdom. The number of distributions which have been made is 7 and 92 laboratories are now participating. The methods used for preparing and distributing samples are described. Some participating laboratories use the multiple tube method and some use membrane filtration to assess the presence of coliforms and Escherichia coli. The results are, therefore, a mixture of estimated numbers and direct colony counts. In order to compare results from these two different laboratory methods statistical tables have been compiled to show the most likely multiple tube result corresponding to each colony count. Tables relating to two commonly used tenfold dilution series are presented. To illustrate how these tables may be used we present results from a typical quality control distribution. The analyses of these results are generally satisfactory but show a tendency for lower counts using the membrane filtration method and more false negative results with E. coli counts.

Colony Count, Microbial↗
PubMed1988

Purified mu EBP-E binds to immunoglobulin enhancers and promoters.

We describe the purification to apparent homogeneity of the murine immunoglobulin heavy-chain (IgH) enhancer-binding protein mu EBP-E from murine plasmacytoma cells by ion exchange and affinity chromatography. Glycerol gradient sedimentation, UV cross-linking, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis confirm that mu EBP-E is a 45-kilodalton molecular mass protein. Orthophenanthroline-copper chemical nuclease footprinting with purified protein has identified high-affinity binding sites for mu EBP-E within the IgH enhancer at the previously identified site E and at sites within IgH promoters and in the kappa light-chain enhancer. Equilibrium binding studies indicate that the dissociation constants for mu EBP-E binding to site E within the enhancer and to a binding site within the V1 heavy-chain promoter are quite low, about 2 x 10(-11) M. Comparison of four mu EBP-E recognition sequences detects only limited sequence similarity among binding sites.

Animals↗
PubMed1988

Surgical procedures in patients during the tenth decade of life.

The purpose of this study was to determine the outcome of major surgical procedures in patients 90 years of age or older. The records of 46 patients in this age group who underwent surgical procedures were reviewed to determine the outcome and the postoperative quality of life. Overall, the perioperative mortality was 20%. Mortality was not influenced by such risk factors as diabetes mellitus, chronic obstructive pulmonary disease, renal failure, quantity of blood loss, duration of procedure, or total number of hospital days. However, patients with heart disease had a significantly higher mortality rate (78%). Overall, 39% of the patients experienced a subjective deterioration in their mental status after surgery. Of those patients who were ambulatory before surgery, 73% were ambulatory after surgery. Although this study indicates that the perioperative mortality is high and mental status changes frequent in this very elderly age group, the quality of life and longevity of the majority of these patients are good, and vigorous surgical intervention appears warranted.

Aged↗
PubMed1987

Multiple DNA sequence elements are necessary for the function of an immunoglobulin heavy chain promoter.

Sequences required for the function of the mouse V1 immunoglobulin heavy chain variable-region (VH) promoter were identified by transient transfection of the normal and mutated promoters into plasmacytoma cells. Our results identify four regions required for normal promoter function: (i) the octamer ATGCAAAT, previously identified by others; (ii) a heptamer, CTAATGA; (iii) a pyrimidine-rich region; and (iv) a region between positions -125 and -251 relative to the transcription start site. Sequence analysis of 19 mouse and human VH 5' flanking regions shows that the heptamer and pyrimidine stretch are strongly conserved. We have also demonstrated that the octamer functions in an orientation independent manner in the VH promoter.

Animals↗