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Biomedical subjects

R Moore

Publications and source records attributed to R Moore.

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

Molecular characterization of a testis-specific estrogen sulfotransferase and aberrant liver expression in obese and diabetogenic C57BL/KsJ-db/db mice.

Sulfation represents a major pathway for the inactivation of steroid hormones such as estrogens and is catalyzed by a group of enzymes called sulfotransferases. Aberrant regulation of an estrogen sulfotransferase has been demonstrated previously in the livers of obese and diabetogenic C57BL/KsJ-db/db strain mice. In this paper, we report the molecular cloning and functional characterization of a full-length complementary DNA for estrogen sulfotransferase from mouse testis. The mouse estrogen sulfotransferase complementary DNA encodes 295 amino acids. It shares 88%, 77%, 75%, and 68% identity in amino acid sequence with the rat liver, human liver, guinea pig adrenal, and bovine placental estrogen sulfotransferase, respectively. The mouse enzyme was expressed as a glutathione-S-transferase fusion protein in Escherichia coli. The fusion protein was affinity purified, and milligram quantities of pure enzyme were obtained after cleavage of the fusion protein with thrombin. The expressed enzyme exhibits a high substrate specificity toward estrogens, including estradiol and estrone. Neither dehydroepiandrosterone, pregnenolone, testosterone, nor a simple phenolic compound, 4-nitrophenol appears to be a substrate. Northern hybridization indicates that messenger RNA (1.3 kilobases) for the estrogen sulfotransferase is expressed exclusively in the testes in control C57BL/KsJ mice. However, both the messenger RNA and protein are dramatically induced in the livers of obese and diabetogenic C57BL/KsJ-db/db mice. In contrast to the liver, the constitutive expression of the enzyme in the testis is not affected by the db/db genotype. These results recapitulate the species-specific nature in the tissue distribution of estrogen sulfotransferase and suggest complex regulatory mechanisms in its expression under normal and pathophysiological conditions.

Amino Acid Sequence↗
PubMed1995

Effect of alpha-tocopherol on antioxidants, lipid peroxidation, and the incidence of pulmonary hypertension syndrome (ascites) in broilers.

Research has demonstrated a compromised antioxidant capacity in broilers with pulmonary hypertension syndrome (PHS). Thus, the objective of the present study was to assess the effects of vitamin E on PHS-induced mortality, tissue antioxidants, and plasma lipid peroxides in male broilers. Control broilers were provided normal ventilation but others, maintained under low ventilation conditions to induce PHS, were randomly assigned to nonimplanted (NI), placebo (PL), or vitamin E (VE) implanted groups. The VE implant released a total of 15 mg of alpha-tocopherol from 0 to 3 wk of age. Tissues and blood samples were obtained at 3 and 5 wk of age from birds with (PHS+) and without (PHS-) PHS. Five-week PHS cumulative mortality was lowered by alpha-tocopherol with mortality rates of 3.6, 4.2, 11.9, and 11.8%, for Controls, VE, NI, and PL groups, respectively. The PHS+ birds exhibited lower body weights, higher hematocrit, right ventricular hypertrophy, lower alpha-tocopherol and glutathione (GSH) concentrations in liver and lung, as well as indicators of oxidative stress, including elevated plasma lipid peroxides and lower oxidized GSH in liver and erythrocytes, at 5 wk of age. All birds exhibited lower erythrocyte catalase activity at 5 than at 3 wk of age. An improved antioxidant capacity was observed in VE birds, including higher liver and lung alpha-tocopherol at 3 and 5 wk, higher liver GSH at 3 wk, and lower plasma lipid peroxide values at 5 wk of age. Direct correlations observed between body weight and plasma lipid peroxides at 3 wk (r = .45) and between right ventricular hypertrophy and plasma lipid peroxides at 5 wk (r = .48), suggests that lipid peroxidation plays a role in the etiology of PHS. The results indicate that the VE implant was effective in lowering PHS-induced mortality in broilers apparently by attenuating processes leading to lipid peroxidation.

Analysis of Variance↗
PubMed1994

Socioeconomic studies of high-level nuclear waste disposal.

The socioeconomic investigations of possible impacts of the proposed repository for high-level nuclear waste at Yucca Mountain, Nevada, have been unprecedented in several respects. They bear on the public decision that sooner or later will be made as to where and how to dispose permanently of the waste presently at military weapons installations and that continues to accumulate at nuclear power stations. No final decision has yet been made. There is no clear precedent from other countries. The organization of state and federal studies is unique. The state studies involve more disciplines than any previous efforts. They have been carried out in parallel to federal studies and have pioneered in defining some problems and appropriate research methods. A recent annotated bibliography provides interested scientists with a compact guide to the 178 published reports, as well as to relevant journal articles and related documents.

Government Agencies↗
PubMed1994

Toxicokinetics of oxazepam in rats and mice.

The comparative toxicokinetics of oxazepam were studied in F344 rats, B6C3F1 mice, and Swiss-Webster mice of both sexes after an i.v. dose of 20 mg/kg and oral gavage doses of 50, 200, and 400 mg/kg. In addition, the toxicokinetics of oxazepam in a 3-week dosed-feed study of male B6C3F1 mice at 125 and 2500 ppm were also investigated. Results indicated that the elimination of oxazepam from plasma after i.v. injection in both rats and mice were first-order and could be best described by a two-compartment model with a terminal elimination half-life of 4-5 h for rats and 5-7 h for mice. After oral gavage dosing the peak oxazepam plasma concentrations in most rodents were reached within 2-3.5 h. At all doses studied, female rodents had significantly higher plasma concentrations than males. Absorption of oxazepam was significantly extended at higher oral doses of 200 and 400 mg/kg. At 50 mg/kg, the bioavailability of oxazepam in rats (< 50%) was lower than in Swiss-Webster mice (> 80%). The bioavailability of oxazepam in both B6C3F1 and Swiss-Webster mice decreased with increasing dose. A dose proportionality of Cmax was not observed in rats and mice after gavage doses of 50, 200, and 400 mg/kg. Plasma concentrations of oxazepam in the dosed-feed study increased with the concentration of oxazepam in the feed, a quasi-steady-state of plasma concentrations of oxazepam was reached after approximately 4 days ad libitum exposure. In B6C3F1 mice, the estimated relative bioavailability of oxazepam from dosed feed (relative to gavage study at 50 mg/kg) was about 43%.

Animals↗
PubMed1994

Lack of the steroid 15 alpha-hydroxylase gene (Cyp2a-4) in wild mouse strain Mus spretus: rapid evolution of the P450 gene superfamily.

Steroid 15 alpha-hydroxylase P450(15 alpha) and coumarin 7-hydroxylase P450coh genes Cyp2a-4 and Cyp2a-5 are members of the mouse P450 2A subfamily. Whereas Mus musclus domesticus strains contain both genes, wild mouse strain Mus spretus contains only Cyp2a-5. Evolutionarily, therefore, Cyp2a-5 is ancestral to Cyp2a-4. Moreover, the line to Cyp2a-4 descended as recently as 3 million years ago in an ancestral mouse. This evidence implies a rapid evolution of the P450 gene superfamily.

Animals↗
PubMed1994

Benchmarking of the CAP-88 and GENII computer codes using 1990 and 1991 monitored atmospheric releases from the Idaho National Engineering Laboratory.

The CAP-88 environmental radiological assessment computer code was benchmark tested to establish confidence in its results. The results from CAP-88 were compared to the results from the GENII computer code, which has undergone rigorous testing. The codes were benchmarked using 1990 and 1991 monitored atmospheric releases from Idaho National Engineering Laboratory facilities and the results (the effective dose equivalent to the maximally exposed offsite individual) were quantitatively compared using a metric based on the uncertainty in the Gaussian plume model and terrestrial transport models. The results of the benchmark tests were within the 95% acceptance region specified in the test protocol. CAP-88 was found to overpredict effective dose equivalent relative to GENII for elevated releases, largely because CAP-88 calculates a larger atmospheric dispersion factor (chi/Q) than does GENII using the same meteorological data. However, CAP-88 consistently underpredicted effective dose equivalent relative to GENII for ground-level releases. This was because CAP-88 accounts for the processes of plume depletion by dry and wet deposition while GENII does not account for these processes. The effect of depletion was tested and found to be most important for a ground-level release of a highly depositing species such as radioiodine which implies that acceptable benchmark results would be difficult to obtain for a highly dopositing species.

Computer Simulation↗
PubMed1994

Group therapy compared with individual desensitization for dental anxiety.

Effects of group therapy (GT) on extreme dental anxiety were compared with individual treatment (IT). Results by scales of dental anxiety, beliefs or trust in dentists, and fear of the next dentist after specialist treatment showed reduced dental anxiety and improved dental beliefs compared with a static control group of 45 patients. The 30 GT patients showed no significant difference in dropouts during training compared with the 68 IT patients, but for patients who completed treatment, GT (n = 24) had greater dental anxiety reduction than IT subjects (n = 60). GT patients required fewer therapist hours per patients than did either of the two IT methods, but time saved in GT did not reach significance over clinical rehearsal IT. Results at 1-yr follow-up after specialist treatment indicated that dropouts were significantly greater in group therapy. Rehearsal IT performed best for sustained dental care behavior. Group dynamics are discussed and suggestions made for effective and efficient group therapy as well as decision making about choice of treatment.

Adult↗
PubMed1994

Cryptosporidium parvum infection of Caco-2 cell monolayers induces an apical monolayer defect, selectively increases transmonolayer permeability, and causes epithelial cell death.

Caco-2 cells were grown on permeable filters and infected with Cryptosporidium parvum. Infection rates exceeded 50% of target cells with a sufficient inoculum dose of parasites. Infection induced a dose- and time-dependent fall in transmonolayer resistance, which was closely related to both the inoculum dose and the number of parasites detected by immunofluorescence. Caco-2a, MDBK, and MDBK subclone F5D2 evidenced similar declines in resistance when grown and infected under similar circumstances. Caco-2 monolayers became permeable to molecules of < or = 1,000 Da but continued to remain impermeable to exogenously added, or endogenously produced, proteins of > or = 1,881 Da. We found that infected monolayers released up to 50% of the total cellular lactase dehydrogenase into apical media, but not basal media, and that the vital dye propidium iodide avidly stained infected cells, and often parasites, when added to the apical reservoir. Cryptosporidium infection of Caco-2 monolayers increases transmonolayer permeability, induces an apical cellular and monolayer defect, and causes cell death.

Animals↗
PubMed1994

Enterocytes adhere preferentially to collagen IV in a differentially regulated divalent cation-dependent manner.

Minor cell defects in epithelial sheets are a consequence of superficial injury in natural intestinal diseases. These defects are restored by migration of shouldering epithelial cells over the underlying matrix. Restitution of minor epithelial defects is facilitated by collagen IV (R. Moore, J. Madri, S. Carlson, and J. L. Madara. Gastroenterology 102: 119-130, 1992). Here we characterize enterocyte attachment to substrates and determine the role of divalent cations. Attachment and spreading of native intestinal epithelial cells (EC) isolated by mechanical vibration were greatest on collagen IV [compared with collagen I, collagen III, laminin, fibronectin, and plastic; P < 0.001]. Attachment was not inhibited by cycloheximide but was inhibited by cytochalasin D and by a functionally defined antibody to collagen IV. In fixed extracellular 1.25 mM Mg2+, EC attachment was nearly three times greater in nominally Ca(2+)-free medium compared with 5 mM Ca2+ (P < 0.001). Conversely, in fixed 1.25 mM Ca2+, cell attachment was three times greater in the presence of 2.5 mM Mg2+ compared with Mg(2+)-deplete media (P < 0.001). Last, in the presence of the intracellular Ca2+ chelator 1,2-bis(2-amino-phenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester, EC attachment was diminished by > 50% (P < 0.001). We speculate that local tissue concentrations of divalent cations may play an important role in restitution of intestinal epithelial wounds by mediating attachment of migrating EC to collagen IV.

Animals↗
PubMed1994

Poststernotomy fractures and pain management in open cardiac surgery.

STUDY OBJECTIVES: To assess whether (1) there is an increased incidence of sternal fractures associated with internal mammary artery (IMA) revascularization in open heart surgery and (2) there is a higher incidence of pain in postoperative patients with sternal fractures. METHODS: Two hundred eighty-eight consecutive adult patients who had undergone cardiac surgery underwent median sternotomy from 1989 to 1991. IMA revascularization was used in 94 patients. The remainder underwent conventional saphenous vein graft (SVG) revascularization or other open cardiac procedure. The sternum was checked for fracture at the time of chest-wall closure. Lung volumes, arterial blood gases, respiratory rate, and oxygen requirements were measured before and after pain relief by intravenous or epidural analgesia. RESULTS: Of 288 consecutive median sternotomies, there were a total of 24 sternal fractures. IMA harvesting was associated with a significantly greater incidence of sternal fractures. In the 94 patients in whom IMA mobilization was used, there were 16 fractures; in the remaining 194 cases, there were 8 fractures (p < 0.007). Twenty-one of 24 patients were not seriously affected by their sternal fractures, whereas 3 patients suffered major respiratory compromise due to postoperative pain. Epidural analgesia was effective treatment for these three cases of severe sternal fracture pain and was not associated with any adverse consequences. All three patients had significant improvement in their respiratory condition after epidural analgesia was instituted. Respiratory rate decreased from 27 +/- 3 to 18 +/- 0.3 breaths/min (p < 0.001) and end maximum inspired volume increased from 700 +/- 1 mL to 1,525 +/- 275 mL. CONCLUSIONS: The use of sternal retraction devices for IMA harvesting in coronary bypass procedures results in an increased incidence of sternal fractures when compared with conventional SVG bypass procedures. Although most sternal fractures are well tolerated, some patients with fractures can become a significant pain management problems. Epidural analgesia is a safe and effective treatment for severe pain associated with sternal fractures and provided improved postoperative pulmonary function.

Adult↗
PubMed1994

Toxicokinetics of pentachlorophenol in the F344 rat. Gavage and dosed feed studies.

1. The toxicokinetics of pentachlorophenol (PCP) were studied in the Fischer 344 rat using i.v. and oral (gavage, dosed feed) routes of exposure. 2. Only minor sex differences were observed in the elimination kinetics of PCP after i.v. administration at 5 mg/kg. 3. Absorption of PCP from the gastrointestinal tract after gavage doses of 9.5 and 38 mg/kg in aqueous methylcellulose vehicles was first order with an absorption half-life of about 1.3 h. 4. The absorption rate constant of PCP from doses feed was comparable with that obtained from aqueous methylcellulose gavage formulations. 5. Bioavailability of PCP administered in dosed feed was significantly lower than the bioavailability of PCP administered by gavage. 6. Dose proportionality was established to a dosage of at least 38 mg/kg. 7. Daily fluctuation of PCP plasma concentrations was observed during the dosed feed study with peak and trough concentrations occurring in early morning and late afternoon, respectively. 8. The time course of PCP plasma concentrations during the dosed feed study were simulated using a computer model based on linear theory. The simulations were comparable with the experimentally determined concentrations.

Animals↗
PubMed1994

A double-blind, randomized, placebo-controlled study of nifedipine on early renal allograft function.

A double-blind, randomized, placebo-controlled study was conducted to determine the effect of nifedipine on early renal allograft function when added to a triple therapy immunosuppression regime comprising low-dose cyclosporin (CsA), prednisolone and azathioprine. Fifty adult cadaveric renal allograft recipients were randomized to placebo (group P n = 17), nifedipine 10 mg preoperatively and 20 mg b.d. postoperatively for 48 h, followed by matching placebo for 3 months (group NS n = 16) or nifedipine 10 mg preoperatively and 20 mg b.d. postoperatively for 3 months (group NL n = 17). Donor and recipient exclusion criteria included recent calcium antagonist treatment. At 3 months after transplantation mean GFR adjusted for graft loss was significantly higher in group NL than in NS (mean +/- SD 61 +/- 28 versus 34 +/- 25 ml/min/1.73 m2; P < 0.05), group P being intermediate (45 +/- 34 ml/min/1.73 m2). Similarly, effective renal blood flow (ERBF) at 3 months was higher in group NL than in groups P and NS (mean +/- SD 351 +/- 175 versus 216 +/- 166 and 220 +/- 162 ml/min/1.73 m2; P < 0.05). The differences were not significant by 6 months post-transplantation. This study suggests that oral nifedipine commenced preoperatively and continued for 3 months following transplantation has beneficial effects on early renal allograft function when incorporated as part of an immunotherapy regimen based on cyclosporin.

Adult↗
PubMed1994

The occurrence of non-01 Vibrio cholerae in non-potable water samples in Barbados.

Fourteen freshwater or brackish-water samples taken from different sites were examined for the presence of Vibrio cholerae. Standard enrichment techniques, using pre-incubation in alkaline peptone water and plating on thiosulfate citrate bile sucrose agar (TCBS) followed by biochemical, physiological and morphological characterization of the isolates, revealed the presence of Vibrio cholerae at nine of the sites examined. Serotyping for type 01 only was performed. All the strains isolated were non-01 Vibrio cholerae.

Bacteriological Techniques↗
PubMed1993

Heterogeneity in MLL/AF-4 fusion messenger RNA detected by the polymerase chain reaction in t(4;11) acute leukemia.

We have designed a single polymerase chain reaction (PCR) primer pair that detects the MLL/AF-4 fusion mRNA encoded by the derivative 11 chromosome from t(4;11)(q21;q23) leukemia cells using the reverse transcriptase PCR technique. PCR amplification was possible in seven of seven cells studied. Sequencing of the amplified products showed three different breakpoints on 11q23 and three on 4q21, resulting in six unique fusion sequences. All fusion sequences maintained an open reading frame. The areas of the MLL and AF-4 genes that are conserved in all derivative 11 fusion RNAs and therefore likely to contribute to the function of the oncogenic fusion protein are centromeric regions of MLL through exon 6 (retaining the AT hook motif) and telomeric regions of AF-4 beginning at codon 491 (containing nuclear localization and GTP-binding motifs). A single primer pair was able to detect the derivative 11 fusion transcript in seven of seven cases of t(4;11) acute leukemia tested. Given the variability shown in specific fusion sequences, studies correlating differential exon usage with clinical parameters will require different fusion-specific oligonucleotides or PCR primer pairs.

Adolescent↗