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Biomedical subjects

G Moore

Publications and source records attributed to G Moore.

At least 91 records · Page 5Linked to original sources
PubMed1994

A family of related sequences associated with (TTTAGGG)n repeats are located in the interstitial regions of wheat chromosomes.

A family of related sequences associated with (TTTAGGG)n repeats has been cloned from the wheat cultivar Chinese Spring. These sequences reveal a high level of polymorphism between wheat varieties when used as restriction fragment length polymorphism (RFLP) probes. Although this family of sequences contains motifs homologous to the repeats in the telomeres of wheat, they are located at interstitial sites on wheat chromosomes.

Blotting, Southern↗
PubMed1994

The case for case-mix adjustment in practice profiling. When good apples look bad.

OBJECTIVE: To assess the influence of patient characteristics on practice profiling. Using the example of specialty referrals by primary care physicians, we evaluated the impact of adjusting for patient characteristics (age/sex vs case mix) on the estimation of practice variation, the identification of outlier practices, and the evaluation of potential predictors of variation. DESIGN AND SETTING: We applied several measurement strategies to a retrospective cohort of patients (N = 37,830) within 52 physician practices in a large staff-model health maintenance organization during a 1-year period. OUTCOME MEASURES: We calculated unadjusted referral rates and adjusted standardized referral ratios for each physician. Using these, we determined coefficients of variation and statistical "outlier status." RESULTS: Adjustment for patient characteristics decreased the observed variation in referral profiles, with a decrease of more than 50% in the coefficient of variation. Three quarters of the physicians identified as statistical outliers with use of an age/sex-adjusted measure were no longer identified as such with use of an case-mix-adjusted measure. Several key predictors of unadjusted referral rate (including physician age, practice tenure, site of practice, and extent of laboratory test ordering) dropped out of regression models when the outcome variable was adjusted for patient characteristics. CONCLUSION: Failure to adjust for case mix in physician practice profiles may lead to overestimates of variation and misidentification of outliers. To the extent that unadjusted practice profiles are used for decisions about education, sanctions, or employment, physicians may be subject to inequitable decisions and actions. Misinformation about the causes and extent of practice variation may also lead to misdirection of scarce resources for quality improvement efforts.

Age Factors↗
PubMed1994

Implication of mRNA binding proteins in the regulation of cyclo-oxygenase in human amnion at term.

The onset of labour is associated with an increase in prostaglandin synthesis in amnion which appears to be mediated at least in part by an increase in cyclo-oxygenase (COX) expression. We have tested the hypothesis that COX expression is controlled in amnion by the binding of a protein to the COX mRNA which may inhibits its translation, as has been seen in vascular smooth muscle cells. Using differential RNA extraction protocols which extract either total mRNA or only mRNA which is not protein bound, we have found that, in amnion, the increase in COX-2 expression seen after the onset of labour is entirely in the protein bound fraction. Unlike in vascular smooth muscle, increased expression of COX-2 in amnion cells is therefore associated with increased rather than decreased protein binding to the mRNA. This protein may be involved in translation initiation or elongation or in mRNA stability. There does not appear to be a protein bound COX-1 mRNA fraction.

Amnion↗
PubMed1994

On the mechanisms of 3-tert-butyl-4-hydroxyanisole- and its metabolites-induced cytotoxicities in isolated rat hepatocytes.

The cytotoxic effects of 3-tert-butyl-4-hydroxyanisole (BHA) and its metabolites, 3-tert-butylhydroquinone (tBHQ) and 3-tert-butyl-4,5-dihydroxyanisole (BHA-OH), were investigated in freshly isolated rat hepatocytes. These compounds caused a time-dependent cell death accompanied by loss of intracellular ATP, glutathione (GSH) and protein thiols at concentration of 0.5 mM. Supplementation of the hepatocyte suspension with 5 mM N-acetylcysteine, a precursor of intracellular GSH, significantly delayed the onset of cytotoxicity induced by BHA-OH and tBHQ; the loss of intracellular ATP, GSH and protein thiols was also prevented. Although N-acetylcysteine did not affect BHA disappearance in the cell suspension, disappearance of tBHQ and formation of tBHQ-GSH conjugate were stimulated by N-acetylcysteine. In addition, N-acetylcysteine prevented BHA-OH disappearance and 3-tert-butyl-5-methoxy-1,2-benzoquinone (BHA-Q) formation. In isolated hepatic mitochondria, BHA, tBHQ and BHA-OH impaired respiration related to oxidative phosphorylation; tert-butylquinone (tBQ) and BHA-Q, quinones derived from tBHQ and BHA-OH, resulted in the significant inhibition of mitochondrial respiration. These results indicate that BHA-OH is the most cytotoxic followed by tBHQ and BHA and that protein thiols and mitochondrial respiratory system are important targets for BHA and its intermediates.

Acetylcysteine↗
PubMed1994

The relative abundance of type 1 to type 2 cyclo-oxygenase mRNA in human amnion at term.

The onset of labor in humans is associated with an increase in prostaglandin production. One of the key steps is the conversion of arachidonic acid to prostaglandin E2 by cyclo-oxygenase (Cox). Cox has been found to exist as two distinct genes, Cox-1 and Cox-2. We have used RT-PCR to study the relative abundance of mRNA from each Cox gene in amnion at term. Quantitation of PCR efficiency indicated an approximate 100 fold excess of Cox-2 messenger RNA over that for Cox-1. These data point to the importance of Cox-2 in the increased prostaglandin synthesis associated with labor. Further studies should therefore focus on the control mechanisms for Cox-2.

Amnion↗
PubMed1994

Human maternal uniparental disomy for chromosome 16 and fetal development.

Two severely growth-retarded fetuses found to have maternal uniparental disomy (UPD) for chromosome 16 and trisomy 16 placental mosaicism both had an unfavourable outcome. Antenatally, the first case was complicated by an unexplained raised maternal serum alpha-fetoprotein concentration, preterm premature rupture of the membranes, and growth retardation detectable at 21 weeks' gestation, whilst the other had an unexplained raised maternal serum human chorionic gonadotrophin level, a two-vessel cord on ultrasound, and cessation of growth at 25 weeks. At post-mortem, both babies had an imperforate anus. Fetal maternal UPD may explain the poor outcome that occurs in some cases of confined placental mosaicism for chromosome 16 and is also associated with specific fetal abnormalities.

Adult↗
PubMed1994

Clinical utility of fetal RhD typing in alloimmunized pregnancies by means of polymerase chain reaction on amniocytes or chorionic villi.

OBJECTIVE: Our purpose was to describe the clinical utility of a deoxyribonucleic acid amplification method for determining fetal RhD status in alloimmunized pregnancies STUDY DESIGN: Six RhD-negative women with alloimmunized pregnancies and heterozygous partners underwent amniocentesis (n = 5) or chorionic villus sampling (n = 1). Fetal RhD type was determined by polymerase chain reaction and results disclosed to the attending physicians. RESULTS: Knowledge of the fetal RhD status avoided further invasive procedures in two pregnancies and facilitated the timing or performance of intrauterine transfusions in the remainder. CONCLUSIONS: In alloimmunized pregnancies the ability to RhD-type the fetus in amniotic fluid avoids the risks of fetomaternal hemorrhage and increased sensitization associated with fetal blood sampling or chorionic biopsy. This allows more rational pregnancy management, avoiding invasive procedures in the presence of an RhD-negative fetus, or planning therapeutic interventions or offering termination of pregnancy in the presence of an RhD-positive fetus.

Amniotic Fluid↗
PubMed1994

Characterization of an Actinobacillus pleuropneumoniae seeder pig challenge-exposure model.

Five strains of Actinobacillus pleuropneumoniae serotype 1 were used to intranasally infect 5 groups of pigs. Using each bacterial strain, infected pigs (termed seeder pigs) were commingled for 48 hours with 5 groups of noninfected test pigs, then were removed. Seeder and test pigs were maintained in isolation and were observed for 14 days. Seeder pigs had mortality that was threefold greater than that of test pigs (24% vs 8%). Rectal temperature in excess of 40.3 C was achieved for 84% of test pigs and 88% of seeder pigs. Neither of these 2 variables was statistically different between the 2 groups of pigs. Clinical impression scores > or = 2 (on a 0 to 3 scale) were three-fold (64% vs 20%) greater for seeder than for test pigs (P < 0.05). The total number of bacterial isolations or nonrecoverable isolates was tabulated for test and seeder pigs' lungs at necropsy, irrespective of the amount of lesions. The number of A pleuropneumoniae isolations was not statistically different between test and seeder pig populations. Recovery of Pasteurella multocida or other bacteria was greater from the seeder pigs (P < 0.05), whereas the number of non-recoverable isolates was greater from test pigs than from seeder pigs (P < 0.05). Assessment of lung lesions at necropsy by either visual estimation or on a weight basis were in agreement.(ABSTRACT TRUNCATED AT 250 WORDS)

Actinobacillus Infections↗
PubMed1993

Cytotoxic effects of biphenyl and hydroxybiphenyls on isolated rat hepatocytes.

The cytotoxic effects of biphenyl (BP) and its hydroxylated derivatives, o-phenylphenol (OPP), m-phenylphenol (MPP), p-phenylphenol (PPP), 2-biphenylyl glycidyl ether (OPP-epoxide), phenyl-hydroquinone (PHQ), o,o'-biphenol (o,o'-BPol) and p,p'-biphenol (p,p'-BPol), were investigated in freshly isolated rat hepatocytes. OPP, MPP and PPP, at concentration of 0.75 mM, resulted in the loss of intracellular ATP, glutathione (GSH) and protein thiols, causing cell death. OPP-epoxide and BP were less toxic than the OPP isomers. MPP or PPP compared with OPP caused serious impairments in oxidative phosphorylation in mitochondria isolated from rat liver. PHQ (0.75 mM) caused a rapid loss of intracellular ATP which preceded the onset of cell death. PHQ was more toxic than o,o'-BPol or p,p'-BPol. PHQ dissolved in Krebs-Henseleit buffer without hepatocytes was rapidly converted to its corresponding quinone, phenyl-benzoquinone. The cytotoxicity produced by PHQ depends on the rate of formation of reactive intermediates. These results indicate that the addition of a hydroxyl group to the aromatic ring of BP enhances BP-induced cytotoxicity and that the mitochondria are a common target of the OPP isomers and other BP derivatives. In addition, the para- or meta-hydroxyl groups rather than the ortho-hydroxyl group increase the toxicity. The cytotoxicity produced by PHQ depends on the rate of formation of reactive intermediate(s) such as phenyl-benzoquinone.

Animals↗
PubMed1993

Key features of cereal genome organization as revealed by the use of cytosine methylation-sensitive restriction endonucleases.

Unlike mammalian genomes, cereal (Gramineae) genomes exhibit little suppression of CpG dinucleotides. In cereal genomes, however, most of the numerous potential recognition sites for CpG methylation-sensitive restriction enzymes are methylated. Analysis of cereal genomic libraries and of regions flanking genes indicates that unmethylated NotI sites are useful landmarks for regions containing genes/single-copy sequences. Studies of a rye chromosome arm indicate that its pericentromeric region has a reduced density of unmethylated NotI (and MluI) sites and therefore of genes. Unmethylated MluI and NruI sites are distributed nonrandomly in the genomes of wheat, barley, and rice. Analysis of the genomic blocks defined by these sites in wheat and barley indicates that they are most likely to have arisen by amplification. These observations form the basis of a proposed model for the organization and evolution of the wheat, barley, and rice genomes.

Bacterial Proteins↗
PubMed1993

The localization of a gene causing X-linked cleft palate and ankyloglossia (CPX) in an Icelandic kindred is between DXS326 and DXYS1X.

The locus responsible for X-linked, nonsyndromic cleft palate and/or ankyloglossia (CPX) has previously been mapped to the proximal long arm of the human X chromosome between Xq21.31 and q21.33 in an Icelandic kindred. We have extended these studies by analyzing an additional 14 informative markers in the family as well as including several newly investigated family members. Recombination analysis indicates that the CPX locus is more proximal than previously thought, within the interval Xq21.1-q21.31. Two recombinants place DXYS1X as the distal flanking marker, while one recombinant defines DXS326 as the proximal flanking marker, an interval of less than 5 cM. Each of the flanking markers recombines with the CPX locus, giving 2-point lod scores of Zmax = 4.16 at theta = 0.08 (DXS326) and Zmax = 5.80 at theta = 0.06 (DXYS1X).

Abnormalities, Multiple↗
PubMed1993

Stabilisation of a yeast artificial chromosome containing plant DNA using a recombination-deficient host.

The large genomes of many plant species contain numerous dispersed repeat sequences. The problem of large-scale structural instability due to the presence of such repeats in yeast artificial chromosome (YAC) clones was assessed. The feasibility of stabilising plant sequences prone to rearrangement in YACs was demonstrated using a host yeast strain deficient in recombination.

Chromosomes, Fungal↗
PubMed1993

Expression of a common cellular phospholipase A2 by human intrauterine tissues.

A subclone of the three prime (3') end of a human extrapancreatic phospholipase cDNA has been generated using the polymerase chain reaction. This has been used to detect mRNA transcripts in RNA extracted from human amnion, chorion-decidua, placenta and myometrium. The carboxyl-terminus of phospholipases A2 is poorly conserved but hybridisation remained stable under conditions of high stringency. This supports the hypothesis that these tissues express a common cellular phospholipase A2 which is identical to that expressed in platelets.

Amnion↗
PubMed1993

Effects of diethyl maleate on phenyl-hydroquinone-induced cytotoxicity in isolated rat hepatocytes.

1. The effects of diethyl maleate (DEM) on the cytotoxicity of phenyl-hydroquinone (PHQ) and other hydroquinones were studied in freshly isolated rat hepatocytes. 2. Addition of PHQ (0.5 or 0.75 mM) to hepatocytes resulted in dose-dependent cell death accompanied by the abrupt depletion of both GSH and protein thiols and the accumulation of phenyl-benzoquinone (PBQ). 3. Pretreatment with DEM (1.25 mM), which causes an abrupt depletion of cellular GSH in hepatocytes, delayed the onset of PHQ-induced cytotoxicity. The delay correlated with inhibition of PBQ formation. 4. Although the pH of the cell suspension was increased slightly (mean pH 0.18) by incubation under carbogen flow, the addition of DEM to the cell suspension inhibited both the increase in pH and the formation of PBQ from PHQ. 5. In hepatocyte suspensions without DEM, PHQ cytotoxicity was dependent on pH, and toxicity was associated with oxidation of PHQ and accumulation of PBQ. 6. Among other hydroquinones (0.5 mM), tert-butyl-hydroquinone-induced cytotoxicity was decreased by DEM (1.25 mM), but DEM did not affect the cytotoxicity of 2,5-di(tert-butyl)-1,4-benzohydroquinone. 7. PHQ-induced cytotoxicity correlated with the accumulation of PBQ in the cell, and the inhibition of PHQ-induced cytotoxicity by DEM correlated with pH-dependent changes in PBQ formation.

Animals↗
PubMed1993

Overexpression of esterase D in kidney from trisomy 13 fetuses.

Human trisomy 13 (Patau syndrome) occurs in approximately 1 in 5,000 live births. It is compatible with life, but prolonged survival is rare. Anomalies often involve the urogenital, cardiac, craniofacial, and central nervous systems. It is possible that these abnormalities may be due to the overexpression of developmentally important genes on chromosome 13. The expression of esterase D (localized to chromosome 13q14.11) has been investigated in both muscle and kidney from trisomy 13 fetuses and has been compared with normal age- and sex-matched fetal tissues, by using northern analysis. More than a twofold increase in expression of esterase D was found in the kidney of two trisomy 13 fetuses, with normal levels in a third. Overexpression was not seen in the muscle tissues from these fetuses.

Abnormalities, Multiple↗
PubMed1993

Tulopafant, a PAF receptor antagonist, increases capillary patency and prolongs survival in discordant cardiac xenotransplants.

Hyperacute rejection is a serious complication of xenogeneic organ transplantation. It is believed that platelets play a pivotal role in this phenomenon. In this study, we provide the first known evidence of the efficacy of the PAF receptor antagonist, tulopafant, in improvement in graft function and histology of discordant cardiac xenografts. Transplantation of guinea pig hearts into recipient rats resulted in hyperacute rejection. Pretreatment of recipient animals with tulopafant (but not indomethacin) extended rejection time by 4-5-fold. Histological examination revealed marked diminution of both interstitial hemorrhage and deposition of platelet and granulocytes in capillaries of cardiac xenografts when recipient animals were pretreated with tulopafant.

Animals↗