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Biomedical subjects

R Moore

Publications and source records attributed to R Moore.

At least 163 records · Page 9Linked to original sources
PubMed1995

Changes in endogenous cytokines, adhesion molecules and platelets during cytokine-induced tumour necrosis.

The aim of this study was to investigate mechanisms of anti-tumour activity and necrosis induced by combinations of tumour necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma). In a breast cancer xenograft model, locally injected recombinant human TNF-alpha arrested growth of established tumours in the absence of overt necrosis. Macroscopic necrosis occurred when rat IFN-gamma, which had no anti-tumour activity as a single agent, was given systemically. Treatment with TNF-alpha and IFN-gamma caused focal engorgement of tumour capillaries with erythrocytes, intravascular recruitment of polymorphonuclear cells and platelet adherence to the tumour vascular endothelium 4 h after the combined treatment. This was followed by destruction of tumour vascular endothelium and both necrosis and apoptosis of tumour cells. Concomitant with these changes, semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed the increase of stromal (murine) mRNA levels for TNF-alpha, TNF receptor 55 kDa, TNF receptor 75 kDa, intracellular adhesion molecule 1, vascular cell adhesion molecule 1, P-selectin and interleukin 6 (IL-6). Thus, the effect of the combined TNF-alpha and IFN-gamma therapy involved the selective destruction of the tumour vasculature, death of tumour cells and increased expression of a series of stromal cytokines, cytokine receptors and adhesion molecules, which could be implicated in the observed events.

Adenocarcinoma, Mucinous↗
PubMed1995

Differential diagnosis of odontophobic patients using the DSM-IV.

Categories of extreme anxiety for dental treatment were derived using DSM-IV psychiatric criteria. A sample of 40 men and 40 women patients with extreme dental anxiety were initially evaluated with Dental Anxiety Scale (DAS), Trait Anxiety Inventory (STAI-T) and Geer Fear Scale (GFS). Patients all had DAS scores > or = 15 indicating extreme dental anxiety and were further evaluated with clinical interviews, Dental Fear Survey (DFS), Dental Beliefs Survey (DBS) and Mood Adjective Checklist (MACL). Results showed that 46% of 80 patients complained mainly of powerlessness and embarrassment about dental treatment while also having greater DBS scores than other categories, i.e. social phobia. Another 19% reported conditioned specific phobias (pain, drilling, injection, etc.) most often and lower DBS and GFS scores than other groups; while 35% had broader general anxiety complications, such as multiple phobias and agoraphobia with or without general anxiety symptoms (higher GFS and STAI-T compared to others). Symptoms of general anxiety disorder (GAD) were present in 30 of 80 patients, who had greater STAI-T and GFS and lower MACL scores than non-GAD patients. These results have implications for appropriate treatment strategies.

Adult↗
PubMed1995

A DNA methylation site in the male-specific P450 (Cyp 2d-9) promoter and binding of the heteromeric transcription factor GABP.

The Cyp 2d-9 gene encodes the male-specific steroid 16 alpha-hydroxylase in mouse liver and shares a conserved regulatory element (-100TTCCGGGC-93) with another male-specific Slp promoter. As shown with the Slp promoter (N. Yokomori, R. Moore, and M. Negishi, Proc. Natl. Acad. Sci. USA 92:1302-1306, 1995), the male-preferential demethylation also occurs at CpG/-97 in the Cyp 2d-9 promoter. The transcription factor which specifically binds to the demethylated element has been purified. The peptide sequences reveal that the factor consists of GABP alpha and GABP beta 1 with Ets and Notch motifs, respectively. Both DNase I footprinting and gel shift assays indicate that the bacterially expressed glutathione S-transferase-GABP fusion proteins bind to the regulatory element only when CpG/-97 is demethylated. Moreover, Cyp 2d-9 promoter is trans-activated by coexpression of GABP proteins in HepG2 cells. Given the additional results that CpG/-50 of the female-specific steroid 15 alpha-hydroxylase (Cyp 2a-4) promoter is preferentially demethylated in the females, the sex-specific expressions of the P450 genes correlate very well with DNA demethylation. We also conclude that GABP is a methylation-sensitive transcription factor and is a potential transcription activator of the male-specific Cyp 2d-9 promoter.

Amino Acid Sequence↗
PubMed1995

A nuclear factor (NF2d9) that binds to the male-specific P450 (Cyp 2d-9) gene in mouse liver.

Expression of the Cyp 2d-9 (steroid 16 alpha-hydroxylase) gene in mouse liver is male specific in such Mus musculus domesticus strains as FVB/N, whereas the corresponding P450 genes in the wild mouse species Mus spretus are not sex specific in their expression. These parental differences in the gene expressions were independently inherited in F1 offspring from crosses of FVB/N and M. spretus. A 5' flanking sequence (-110CTC CTCCCTATTCCGGGCC-92) was defined as a regulatory element (named SDI-A1) for the domestic Cyp 2d-9 promoter. The nucleotide which corresponds to T at position -99 within SDI-A1 was found to be substituted with C in the wild mouse P450 genes. The placing of C at position -99 abolished the transcriptional activity of SDI-A1 in HepG2 cells as well as the binding of SDI-A1 to a nuclear factor. This factor (designated NF2d9) was purified from mouse nuclear extracts, and its cDNA cloned. The purified NF2d9 bound to SDI-A1 but not to the mutated SDI-A1 with C at position -99. The deduced amino acid sequence revealed that NF2d9 is 72 and 94% identical to mouse CP2 and human LBP-1a, respectively. NF2d9 thus belongs to the CP2 family and is the mouse homolog of human LBP-1a, which modulates human immunodeficiency virus type 1 transcription. Anti-NF2d9, which was raised against the bacterially expressed protein, supershifted the SDI-A1 complex with the liver nuclear extract. Both the bacterially expressed and in vitro-translated NF2d9 inhibited SDI-A1 complex formation, although they did not bind to SDI-A1 directly. The results, therefore, indicate that the domestic Cyp 2d-9 gene can be regulated through a specific association of NF2d9 with SDI-A1.

Amino Acid Sequence↗
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↗