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Biomedical subjects

R Moyer

Publications and source records attributed to R Moyer.

18 recordsLinked to original sources
PubMed2001

Bisulfite-induced cytosine deamination rates in E. coli SSB:DNA complexes.

E. coli single-stranded binding protein (SSB) has been examined for its ability to modulate bisulfite-induced cytosine deamination rates in single-stranded DNA (ssDNA). We used a lacZ alpha-complementation reversion assay to detect C-->U rates at a single codon in M13mp2 DNA, whether in free ssDNA or in an SSB:ssDNA complex. When incubated at 37 degrees C, the average bisulfite-induced reversion rate constant was four-fold less in SSB:ssDNA complexes than in ssDNA, at a single codon. Across a 250 base pair target and over 23 scorable C-->U sites, the forward rate constant was 4.9-fold less in SSB:ssDNA complexes than in ssDNA alone. After treatment with N-uracil glycosylase, ssDNA incubated with bisulfite had reversion frequencies at the background rate of ssDNA incubated without bisulfite, indicating that virtually all mutations scored were due to C-->U events. The decrease in cytosine deamination rates occurred both in a single codon and over a 250 bp target, indicating that interactions between SSB and ssDNA reduce bisulfite-catalyzed mutations. The structural role of SSB is well recognized in multiple cellular processes; SSB can also function to minimize bisulfite-induced ssDNA mutations.

Cytosine↗
PubMed2000

TNF-alpha receptor signaling and IL-10 gene therapy regulate the innate and humoral immune responses to recombinant adenovirus in the lung.

Recombinant adenovirus-mediated gene therapy has demonstrated great promise for the delivery of genes to the pulmonary epithelium. However, dose-dependent inflammation and local immune responses abbreviate transgene expression. The purpose of these studies was to determine the role of TNF-alpha and individual TNF receptor signaling to adenovirus clearance and immune responses, and whether coexpression of human IL-10 could reduce inflammation and extend the duration of transgene expression in the lung. beta-Galactosidase expression in mice receiving intratracheal instillation of Adv/beta-gal (adenovirus construct expressing beta-galactosidase) was transient (less than 14 days), but a significant early increase of beta-galactosidase expression was seen in mice lacking either or both TNF-alpha receptors. Absence of TNF-alpha or the p55 receptor significantly attenuated the Ab response to both adenovirus and beta-galactosidase. Human IL-10 expression in the lung suppressed local TNF-alpha production following AdV/hIL-10 (adenovirus construct expressing human IL-10) delivery, but did not lead to increased or prolonged transgene expression when coexpressed with beta-galactosidase. Expression of human IL-10 following AdV/hIL-10 instillation extended at least 14 days, was nonimmunogenic, and suppressed the development of neutralizing Abs against adenoviral proteins as well as against human IL-10. We conclude that TNF-alpha signaling through both the p55 and p75 receptor plays important roles in the clearance of adenoviral vectors and the magnitude of the humoral immune response. Additionally, although coexpression of human IL-10 with beta-galactosidase had only modest effects on transgene expression, we demonstrate that AdV/hIL-10 is well tolerated, has extended expression compared with beta-galactosidase, and is nonimmunogenic in the lung.

Adenoviridae↗
PubMed1997

Misoprostol for medical evacuation of early pregnancy failure.

OBJECTIVE: To determine whether misoprostol (a prostaglandin E1 analogue) 400 micrograms orally (group 1) or 800 micrograms vaginally (group 2) will cause complete uterine evacuation in women with early pregnancy failure. METHODS: Twenty subjects were recruited for a prospective, non-blinded, randomized clinical trial. Early pregnancy failure was diagnosed by transvaginal ultrasound examination; only women with a closed cervical os and minimal vaginal bleeding were enrolled. Subjects returned 24 hours after misoprostol administration for a transvaginal ultrasound examination. If the gestational sac was still present, the misoprostol dose was repeated and the subject returned again 24 hours later. Subjects who failed to expel the pregnancy were offered a suction curettage. RESULTS: Twelve and eight women were randomized to groups 1 and 2, respectively. Complete uterine evacuation occurred in three of 12 [25%, 95% confidence interval (CI) 1%, 50%] and seven of eight (88%, 95% CI 65%, 100%, P = .010) subjects in groups 1 and 2, respectively. Vomiting occurred in 30% and 13%, respectively, and diarrhea in 50% and 38%, respectively. CONCLUSION: Vaginal misoprostol 800 micrograms is more effective than oral misoprostol 400 micrograms for uterine evacuation of early pregnancy failure and may be an effective alternative to dilation and curettage.

Abortifacient Agents, Nonsteroidal↗
PubMed1996

Accuracy of MRI patterns in evaluating anterior cruciate ligament tears.

The purpose of this study was to determine the different patterns of anterior cruciate ligament (ACL) tears on MRI and the prevalence and accuracy of these patterns. Images were obtained on high-tesla and low-tesla units and the results compared to determine whether field strength affects the interpretation using the grading system. In 172 patients who underwent knee MRI (109 knees with high-tesla units and 63 knees with low-tesla units) and arthroscopy, there was a total of 91 arthroscopically proven ACL tears. Five patterns of ACL tears were observed and designated as type 1 (diffuse increase in signal on T2-weighted images and enlargement of the ligament, 48%); type 2 (horizontally oriented ACL, 21%); type 3 (nonvisualization of the ACL, 18%); type 4 (discontinuity of the ACL, 11%); and type 5 (vertically oriented ACL, 2%). The positive predictive value (PPV) for type 2, 4, and 5 patterns was 100% for both field strengths: for type 3 PPV was just above 80% for both field strengths. The PPV value for type 1 was 90% for the high-tesla unit and 79% for the low-tesla, unit, which was not statistically significant. Combining the results of both field strengths, the overall sensitivity and specificity were 93% and 89%, respectively. Arthroscopic results were also used to determine the association between meniscal and ACL tears. Only 13% of ACL tears were isolated, the rest being associated with meniscal tears. Forty-five percent of medial meniscal and 50% of lateral meniscal tears were associated with an ACL tear, and 94% of ACLs were torn when both menisci were torn.

Adolescent↗
PubMed1993

Echinomycin, a bis-intercalating agent, induces C-->T mutations via cytosine deamination.

Echinomycin, a bis-intercalating, antitumor drug, has been studied for its ability to induce the deamination of cytosine to uracil (C-->U) in double-stranded DNA. We have employed a sensitive lacZ alpha-complementation reversion assay to detect G.C-->A.T mutations at a number of sites in M13mp2 DNA to determine the extent to which distortions of DNA structure induced by echinomycin may affect C-->U rates. When double-stranded M13mp2 DNA with a 12-base target containing a CpG site was incubated at 37 degrees C, the reversion frequency of the echinomycin-treated DNA increased linearly over time, with a rate constant 3-fold greater than DNA incubated without echinomycin. Of the 11 ways that blue pseudo-revertants can occur in the target, 96% of the observed revertants arose from C-->T and tandem CC-->TT transitions, with 78% attributable to single-base C-->T changes at three sites. Transfection into ung+ cells decreased the reversion frequencies by 85% to near background levels, indicating that the increase in C-->T mutations was due to deamination of C to U. The cytosine deamination rate constants for the entire target at pH 6.0 and 37 degrees C were 1.2 x 10(-11) sec-1 for untreated DNA and 3.5 x 10(-11) sec-1 for echinomycin-treated DNA. The increase in C-->T mutation rates occurred at cytosines both proximal and distal to a CpG echinomycin-binding site. We hypothesize that this increase in deamination rate is due to a more open or single-stranded DNA structure caused by the echinomycin: DNA interaction.

Base Sequence↗
PubMed1993

MR imaging of the knee: expanded classification and pitfalls to interpretation of meniscal tears.

Findings from magnetic resonance (MR) imaging examinations of 194 knees were interpreted retrospectively with a new classification, including not only signal intensity but morphologic abnormalities. All findings were correlated with prospectively recorded results from arthroscopic examinations performed by a knee subspecialist. Meniscal MR imaging findings were expanded to eight types in this study. Positive predictive values for each type of finding and overall accuracy were calculated. Several potential sources of error that could be differentiated through pathologic change were recognized. Sensitivity and specificity of MR imaging findings were, respectively, 95% and 74% for the medial meniscus and 86% and 90% for the lateral meniscus. As the classification grade increased, the likelihood of meniscal tear also increased. Medial meniscal tears tended to occur in a predictable pattern, extending from the posterior to the anterior horn. Thus, when a definite tear of the body or anterior horn of the medial meniscus is present, a tear of the posterior horn should be suspected, even if the findings are not convincing. This expanded classification may be useful for radiologists in expressing their level of confidence in a particular MR imaging finding suggestive of meniscal injury.

Adolescent↗
PubMed1992

1987 to 1991 cost and utilization of Class IV HIV patients.

The 1987 to 1991 direct medical costs and service utilization of Class IV Human Immunodeficiency Virus (HIV) patients cared for at a Group Health Cooperative of Puget Sound (GHC) are described and compared across four time periods: 1987-'88, 1989, 1990, and 1991. Cost and utilization information for an age- and sex-matched control group of GHC enrollees not having Class IV HIV conditions are also compared to those of the Class IV HIV group. Data are presented on pharmacy, inpatient care, outpatient visits by physician specialty, laboratory, radiology, home health/hospice and other costs. The costs of the Class IV HIV population are, on average, 20 times those of the control group. The percent distribution of the control group's costs did not experience much change from 1989 to 1991. Conversely, the Class IV HIV group experienced a shift in costs from the inpatient to outpatient setting from 1987-'88 to 1989. This shift was temporary, as the locus of care shifted back to the inpatient setting over the following 2 years. Anecdotal evidence suggests that antiretroviral treatment may have led to a period in which patients required less intensive settings to manage their illness. Inpatient costs may have increased as the initial benefit of zidovudine treatment began to wane. The Class IV HIV population had greater percent of total expenses in pharmacy, laboratory, radiology, and home health/hospice services, and lower percent of total expenses in outpatient primary and specialty care than the control group.

Adult↗
PubMed1991

Famotidine (20 mg) b.d. relieves gastrooesophageal reflux symptoms in patients without erosive oesophagitis. Famotidine/GERD Investigation Group.

Previous clinical trials have evaluated a large number of symptomatic individuals with heartburn. Most studies have documented the need for multiple daily dosing with H2-antagonists to achieve clinical and statistical efficacy for symptom relief. The purpose of this study was to compare the safety profile and efficacy of famotidine oral dosing regimens, 40 mg nocte and 20 mg b.d. with placebo in the relief of symptoms in patients suffering from frequent heartburn found to have endoscopically normal oesophageal mucosa or mild non-erosive oesophagitis. Famotidine (20 mg) b.d. reduced and eventually completely relieved gastro-oesophageal reflux disease symptoms in most patients during the 6-week trial. Global assessment of improvement at 2 and 6 weeks indicated significantly greater improvement with a b.d. treatment regimen than with either a 40 mg nocte or placebo treatment. No statistically significant differences between famotidine and placebo in the number of patients who experienced clinical adverse experiences were noted and no serious adverse events attributable to famotidine occurred. Based upon these findings, patients with gastro-oesophageal reflux symptoms experience good relief of their complaints with twice daily famotidine in standard doses.

Administration, Oral↗
PubMed1991

Evaluation of severe reactions to sweat bee stings.

Thirteen patients with severe reactions to sweat bee stings were evaluated. Eleven patients had had systemic reactions and two, large local reactions. Skin testing and RAST with venom of other Hymenoptera and whole body extract of sweat bees disclosed negative reactions to both skin tests and RAST of all other insects tested in eight, while three showed sensitivity to honey bee. Only one patient had a positive RAST reaction to whole body extract of sweat bee. Whole body extract of sweat bee causes some irritant reaction when skin testing controls and is not a reliable diagnostic agent even though patients were more reactive than controls. Hypersensitivity reactions to sweat bee stings are distinct and not associated with reactions to other stinging insects. Currently, no reliable antigen is commercially available for diagnosing or treating this condition. Sweat bee venom or other venom antigens might be beneficial.

Adult↗
PubMed1989

Site-specific aflatoxin B1 adduction of sequence-positioned nucleosome core particles.

The question of how the presence of nucleosomal packing of DNA modifies carcinogen interaction at specific sites cannot be answered by studies on whole chromatin or bulk nucleosomes because of the heterogeneity of DNA sequences in the particles. We have circumvented this problem by using nucleosomes that are homogenous in DNA sequence and hence in DNA-histone contact points. A cloned DNA fragment containing a sea urchin 5 S gene which precisely positions a histone octamer was employed. By using 32P end-labeled DNA and genotoxins that allow cleavage at sites of attack, the frequency of adduction at every susceptible nucleotide can be determined on sequencing gels. The small methylating agent dimethyl sulfate and the bulky alkylating agent aflatoxin B1-dichloride (AFB1-Cl2) were used to probe the influence of DNA-histone interactions on DNA alkylation patterns in the sequence-positioned core particle. We find dimethyl sulfate to bind with equal preference to naked or nucleosomal DNA. In contrast, AFB1-Cl2 binding is suppressed an average of 2.4-fold at guanyl sites within nucleosomes compared with AFB1-Cl2 affinity at the corresponding site in naked DNA. The DNA is more accessible in regions near the particle boundary. We observe no other histone-imposed localized changes in AFB1-Cl2 sequence specificity. Further, sites of DNase I cleavage or proposed DNA bending show neither enhanced nor reduced AFB1-Cl2 adduction to N7-guanine. Since AFB1-Cl2 binding sites lie in the major groove, nucleosomal DNA appears accessible to AFB1-Cl2 at all points of analysis but with an access which is uniformly restricted in the central 100 nucleotides of the core particle. The data available do not indicate further localized or site-specific perturbations in DNA interactions with the two carcinogens studied.

Aflatoxin B1↗
PubMed1988

Gene-specific differences in the aflatoxin B1 adduction of chicken erythrocyte chromatin.

Mature and immature chicken erythrocyte nuclei were treated with activated aflatoxin B1 (2,3-dichloroaflatoxin B1), producing covalently bound DNA adducts. This reaction produces alkali-labile sites in the DNA which can be identified by using a variation of the Maxam-Gilbert sequencing procedure. We determined the aflatoxin B1 accessibility of defined regions of the erythroid genome by using different specific probes and monitoring the disappearance of similar-sized fragments generated by restriction enzyme digestion. The genes studied were the erythroid-specific beta-globin and histone H5 genes, which are potentially active in mature erythroid nuclei and transcriptionally active in immature erythrocytes, and the vitellogenin and ovalbumin genes, which are both transcriptionally inactive in these cells. The beta-globin and histone H5 genes were more accessible than the repressed vitellogenin and ovalbumin genes to aflatoxin B1 modification in mature and immature erythroid chromatin. Micrococcal nuclease was used to probe the nucleosomal organization of active (beta-globin and histone H5) and repressed (vitellogenin and ovalbumin) genes in chicken erythrocytes. The vitellogenin and ovalbumin genes show a canonical nucleosome repeat pattern in mature and immature chicken erythrocyte nuclei. In contrast, the beta-globin and histone H5 genes lack a distinct nucleosomal repeat pattern in these cells. These results support the hypothesis that transcriptionally active genes are preferentially accessible to carcinogen modification because of their disrupted chromatin structure.

Aflatoxin B1↗
PubMed1987

Comparative binding and sequence interaction specificities of aflatoxin B1, aflatoxicol, aflatoxin M1, and aflatoxicol M1 with purified DNA.

The covalent binding of the activated forms of several aflatoxins to N-7 of guanine residues on purified DNA has been studied. The aflatoxins include aflatoxin B1 (AFB1) and two human metabolites, aflatoxicol and aflatoxin M1, along with aflatoxicol M1, a rabbit and trout metabolite. DNA binding studies using tritiated [3H]aflatoxins indicate that equimolar solutions of each aflatoxin upon activation with chloroperoxybenzoic acid readily react to produce covalently bound adducts. These reactions produce alkali-labile sites which can be identified using a simple variation of the Maxam-Gilbert sequencing procedure. Two DNA fragments were exposed to each aflatoxin, and the reaction intensities at 33 guanine residues were determined. As much as 10-fold variation in reaction intensities was observed for various guanyl sites. Data indicate that none of the aflatoxins had identical reaction profiles, although AFB1 and aflatoxicol M1 were similar, as were aflatoxicol and aflatoxin M1. Hence, the frequency with which the various aflatoxin epoxides might damage specific sites critical for tumor initiation in vivo would not be predictable from total covalent binding indices. The frequency of occurrence of modifications at particular sites for AFB1 was also compared with the empirical "rules" established for AFB1 by Misra et al. (Misra, R. P., Muench, K. F., and Humayun, M. Z. (1983) Biochemistry 22, 3351-3359). Identical sites within fragments were compared for each aflatoxin, and the data showed that the attacking frequency for some such sites varied significantly. These results indicate that binding intensity rules based on nearest neighbor nucleotides do not reliably predict guanyl-AFB1 binding frequencies.

Aflatoxin B1↗
PubMed1981

Induced repair of genetic damage in Neurospora.

Repair of genetic damage in Neurospora has been studied using a procedure in which one strain is exposed to a potentially lethal dose of UV before being joined in a heterokaryon with an undamaged strain. We have monitored the ability of the second strain to rescue the first. The extent of rescue is greatly enhanced when the rescuing strain has itself received a small, nonlethal dose of UV, thus demonstrating an inducible repair system.--The experiment was modified by substituting X rays or nitrous acid for UV as either the damaging agent or the inducing agent. In every combination, induced rescue was observed.--Three repair-deficient mutants (uvs-2, uvs-3 and uvs-6) were substituted for wild type (uvs+) as the rescuing component to find out whether any of them lacked the inducible repair system. Both uvs-2 and uvs-6 demonstrated inducible repair; uvs-3 showed none, but gave a high level of repair without induction, suggesting that it is a regulation (derepressed) mutant of an inducible repair system.

Cell Fusion↗
PubMed1976

Influence of hole shape on collimator performance.

The imaging properties of triangular and hexagonal hole shapes were compared for low energy scintillation camera collimators. The response of both hole shapes was calculated using a ray-tracing computer program, corresponding collimators were constructed and their performance was evaluated by measuring line spread functions and imaging bar patterns. The triangular hole shape was found to give better results above a spatial frequency of 1-5 cycles cm-1, below that frequency the hexagonal hole shape is superior. The differences, however, are small and the superior performance of the hexagonal hole collimator at clinically significant spatial frequencies is barely visible in bar pattern images.

Computers↗
PubMedDate not supplied

Clinical, functional, and radiographic assessments of the conventional and modified Boyd-Anderson surgical procedures for repair of distal biceps tendon ruptures.

The purpose of this study was to evaluate the clinical, functional, and radiographic outcomes of the conventional and modified Boyd-Anderson procedures for repair of distal biceps tendon ruptures. Thirteen of 18 men who underwent surgical repair for unilateral distal biceps tendon ruptures at one university center participated in the study. In general, follow-up outcomes were favorable with respect to return to premorbid activity levels, patient satisfaction with surgical outcome, and overall clinical results. Elbow flexion, forearm supination, and upper extremity functional concentric peak torque and range of motion results were not significantly different between the surgical and nonsurgical arms when dominance was controlled as a confounding factor. Radiographic findings revealed no clinically remarkable signs of heterotopic ossification or proximal radioulnar synostosis. Results of the study reveal that the conventional and modified Boyd-Anderson procedures are clinically, functionally, and radiographically efficacious for repair of distal biceps tendon ruptures.

Adult↗