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Biomedical subjects

R E Johnson

Publications and source records attributed to R E Johnson.

At least 19 recordsLinked to original sources
PubMed1999

Sulfuric acid on Europa and the radiolytic sulfur cycle.

A comparison of laboratory spectra with Galileo data indicates that hydrated sulfuric acid is present and is a major component of Europa's surface. In addition, this moon's visually dark surface material, which spatially correlates with the sulfuric acid concentration, is identified as radiolytically altered sulfur polymers. Radiolysis of the surface by magnetospheric plasma bombardment continuously cycles sulfur between three forms: sulfuric acid, sulfur dioxide, and sulfur polymers, with sulfuric acid being about 50 times as abundant as the other forms. Enhanced sulfuric acid concentrations are found in Europa's geologically young terrains, suggesting that low-temperature, liquid sulfuric acid may influence geological processes.

Ice↗
PubMed1999

hRAD30 mutations in the variant form of xeroderma pigmentosum.

Xeroderma pigmentosum (XP) is an autosomal recessive disease characterized by a high incidence of skin cancers. Yeast RAD30 encodes a DNA polymerase involved in the error-free bypass of ultraviolet (UV) damage. Here it is shown that XP variant (XP-V) cell lines harbor nonsense or frameshift mutations in hRAD30, the human counterpart of yeast RAD30. Of the eight mutations identified, seven would result in a severely truncated hRad30 protein. These results indicate that defects in hRAD30 cause XP-V, and they suggest that error-free replication of UV lesions by hRad30 plays an important role in minimizing the incidence of sunlight-induced skin cancers.

Alleles↗
PubMed1999

Requirement of DNA polymerase activity of yeast Rad30 protein for its biological function.

The RAD30 gene of Saccharomyces cerevisiae encodes a DNA polymerase, Poleta. The Rad30 protein shares homology with the yeast Rev1 and the Escherichia coli DinB and UmuC proteins. Although these proteins contain several highly conserved motifs, only Rad30 has been shown to possess a DNA polymerase activity. To determine whether the DNA polymerase activity of Rad30 was essential for its biological function, we made a mutation in the highly conserved SIDE sequence in Rad30, in which the aspartate and glutamate residues have each been changed to alanine. The mutant Rad30 protein lacks the DNA polymerase activity, and the mutant gene does not complement the rad30Delta mutation. These findings indicate that DNA polymerase activity is indispensable for the biological function of RAD30.

Amino Acid Sequence↗
PubMed1999

Hydrogen peroxide on the surface of Europa.

Spatially resolved infrared and ultraviolet wavelength spectra of Europa's leading, anti-jovian quadrant observed from the Galileo spacecraft show absorption features resulting from hydrogen peroxide. Comparisons with laboratory measurements indicate surface hydrogen peroxide concentrations of about 0.13 percent, by number, relative to water ice. The inferred abundance is consistent with radiolytic production of hydrogen peroxide by intense energetic particle bombardment and demonstrates that Europa's surface chemistry is dominated by radiolysis.

Extraterrestrial Environment↗
PubMed1999

Efficient bypass of a thymine-thymine dimer by yeast DNA polymerase, Poleta.

The RAD30 gene of the yeast Saccharomyces cerevisiae is required for the error-free postreplicational repair of DNA that has been damaged by ultraviolet irradiation. Here, RAD30 is shown to encode a DNA polymerase that can replicate efficiently past a thymine-thymine cis-syn cyclobutane dimer, a lesion that normally blocks DNA polymerases. When incubated in vitro with all four nucleotides, Rad30 incorporates two adenines opposite the thymine-thymine dimer. Rad30 is the seventh eukaryotic DNA polymerase to be described and hence is named DNA polymerase eta.

Adenine↗
PubMed1999

Is cigarette smoking associated with impaired physical and mental functional status? An office-based survey of primary care patients.

OBJECTIVE: To examine the relationship between cigarette smoking and self-reported physical and mental functional status. DESIGN: Cross-sectional survey of 837 patients visiting 2 family-practice centers. Patients completed a self-administered survey about functional status, tobacco use, and demographic characteristics while waiting to be called back for their appointments. SETTING: An inner-city family practice clinic in Richmond, Virginia, and a more affluent suburban practice outside Washington, DC. MAIN OUTCOME MEASURES: Physical and mental functional status, as measured by the SF-36 (Medical Outcomes Trust, Boston, MA); current and former cigarette use; and demographic variables (age, gender, education, income). RESULTS: Among current smokers, self-reported functional status scores were significantly lower than those of nonsmokers in all SF-36 domains (p < or = 0.02), a pattern that was more dramatic for mental functional status domains (social function, vitality, emotional role limitations, mental health). In several SF-36 domains, a dose-response relationship between smoking and functional status was noted. After multivariate adjustment for demographic confounders and practice site, the statistical significance of these differences diminished considerably, but it remained significant for certain domains and for the overall difference across all domains (MANCOVA p = 0.017). CONCLUSIONS: Current smokers report lower functional status than nonsmokers, in physical and especially in mental domains. The meaning of this cross-sectional relationship is unclear without further longitudinal study. Smoking may be associated with other variables that have a causal role.

Adolescent↗
PubMed1999

Head-to-head evaluation of five chlamydia tests relative to a quality-assured culture standard.

Nucleic acid amplification tests offer superior sensitivity for the detection of Chlamydia trachomatis infection, but many laboratories still use nonamplification methods because of the lower cost and ease of use. In spite of their availability for more than a decade, few studies have directly compared the nonamplification tests. Such comparisons are still needed in addition to studies that directly compare individual nonamplification and amplification tests. The purpose of this study was to evaluate and compare the performance characteristics relative to culture of five different tests for the detection of C. trachomatis with and without confirmation of positive results. The tests were applied to endocervical specimens from 4,980 women attending family planning clinics in the northwestern United States. The five nonculture tests included Chlamydiazyme (Abbott), MicroTrak direct fluorescent antibody (DFA) (Syva), MicroTrak enzyme immunoassay (EIA) (Syva), Pace 2 (Gen-Probe), and Pathfinder EIA (Sanofi/Kallestad). All positive results obtained with a nonculture test (except MicroTrak DFA) were confirmed by testing the original specimens with a blocking antibody test (Chlamydiazyme), a cytospin DFA (MicroTrak EIA and Pathfinder EIA), and a probe competition assay (Pace 2). The prevalence of culture-proven chlamydia was 3.9%. The sensitivities of the nonculture tests were in a range from 62 to 75%, and significant differences between tests in terms of sensitivity were observed. The positive predictive value for each test was 0.85 or higher. The specificities of the nonculture tests without performance of confirmations were greater than 99%. Performing confirmatory tests eliminated nearly all of the false positives.

Cervix Uteri↗
PubMed1999

Cranial polyneuropathies in multiple sclerosis: case report and literature review.

Although cranial neuropathies are common disorders in multiple sclerosis patients, multiple cranial nerve involvement is an unusual occurrence. Correlation of clinical symptoms with magnetic resonance imaging evidence of demyelinating central nervous system lesions can confirm the diagnosis. The authors report on the case of a 43-year-old woman who initially was thought to have suffered a brainstem infarct but, in fact, had developed multiple cranial nerve functional deficits. Treatment of multiple sclerosis remains primarily supportive in nature, with corticosteroids used for acute exacerbations and chronic progression.

Adult↗
PubMed1998

Identification of APN2, the Saccharomyces cerevisiae homolog of the major human AP endonuclease HAP1, and its role in the repair of abasic sites.

Abasic (AP) sites arise in DNA through spontaneous base loss and enzymatic removal of damaged bases. APN1 encodes the major AP-endonuclease of Saccharomyces cerevisiae. Human HAP1 (REF1) encodes the major AP endonuclease which, in addition to its role in DNA repair, functions as a redox regulatory protein. We identify APN2, the yeast homolog of HAP1 and provide evidence that Apn1 and Apn2 represent alternate pathways for repairing AP sites. The apn1Delta apn2Delta strain displays a highly elevated level of MMS-induced mutagenesis, which is dependent on the REV3, REV7, and REV1 genes. Our findings indicate that AP sites are highly cytotoxic and mutagenic in eukaryotes, and that the REV3, REV7-encoded DNA polymerase zeta mediates the mutagenic bypass of AP sites.

Amino Acid Sequence↗
PubMed1998

Induction with levomethadyl acetate: safety and efficacy.

BACKGROUND: Levomethadyl acetate hydrochloride (known as LAAM) is a mu-opioid agonist approved for the treatment of opioid dependence. Clinical trials comparing LAAM and methadone have reported lower patient retention rates during LAAM induction; however, this may reflect dose and schedule differences. Few studies have systematically examined LAAM dose induction. This study compared induction with 3 different LAAM dosage levels. METHODS: In a randomized, double-blind trial, male and female opioid-dependent patients (N = 180) were assigned to 1 of 3 LAAM doses. The low-dose (25 mg) induction was constant from the onset of treatment, the medium-dose (50 mg) induction lasted 7 days, and the high-dose (100 mg) induction lasted 17 days. Safety and efficacy were assessed on retention, urinalysis and self-reported drug use, symptoms, and patient ratings of medication adequacy. RESULTS: The high-dose group had significantly fewer illicit opioid-positive urine samples in weeks 3 and 4 as compared with the low-dose group. The high-dose group had significantly lower self-reported heroin craving in weeks 2 and 3. All groups demonstrated significant decreases in illicit drug use, withdrawal symptoms, and depression. There were no between-group differences in retention; however, there was a trend (P = .08) for lower retention and a greater number of agonist adverse effects were observed in the high-dose group. Overall, LAAM doses were well tolerated by most patients. CONCLUSION: Induction with low and medium LAAM doses can be safely and effectively achieved within 7 days. Induction with higher LAAM doses can be safely achieved within 17 days, but may result in greater rates of patient dropout and opioid agonist adverse effects. Therefore, higher doses should be approached more slowly.

Adult↗
PubMed1998

Toxicokinetics of inhaled 2-butoxyethanol and its major metabolite, 2-butoxyacetic acid, in F344 rats and B6C3F1 mice.

2-Butoxyethanol (2BE) is used extensively in the production of cleaning agents and solvents. It is primarily metabolized in the liver to 2-butoxyacetic acid (2BAA), which is believed to be responsible for 2BE toxicities associated with hemolysis of red blood cells. The objective of the study was to characterize the systemic disposition of 2BE and 2BAA in rats and mice during 2-year 2BE inhalation toxicity studies. Male and female F344 rats and B6C3F1 mice (6-7 weeks old) were exposed to target 2BE concentrations of 0, 31.2, 62.5, or 125 ppm (rats), or 0, 62.5, 125, or 250 ppm (mice), by whole-body inhalation for 6 h/day, 5 days/week for up to 18 months. Postexposure blood samples were collected after 1 day, 2 weeks, and 3, 6, 12, and 18 months of exposure. Postexposure 16-h urine samples were collected after 2 weeks and 3, 6, 12, and 18 months of exposure. A separate set of mice was kept in the control chamber and exposed to 2BE for 3 weeks when they were approximately 19 months old. Postexposure blood samples were collected after 1 day and 3 weeks of exposure and 16-h urine samples were collected after 2 weeks of exposure from these aged mice. Blood samples were analyzed for both 2BE and 2BAA and urine samples were analyzed for 2BAA using GC/MS, and their kinetic parameters were estimated through the curve-fitting method using SAS. Systemically absorbed 2BE was rapidly cleared from blood (t1/2-RAT < 10 min; t1/2-MOUSE < 5 min after the 1-day exposure) independent of exposure concentration. Proportional increases in AUC2BE relative to increases in exposure concentration indicated linear 2BE kinetics. In contrast, the rate of 2BAA elimination from blood decreased as the exposure concentration increased. Nonproportional increases in AUC2BAA also indicated that 2BAA is eliminated following dose-dependent, nonlinear kinetics. Overall, mice eliminated both 2BE and 2BAA from blood faster than rats. Sex-related differences in 2BAA elimination were most significant with rats, in that females were less efficient in clearing 2BAA from the blood. Differences in renal excretion of 2BAA are possibly responsible for the sex-related difference in the 2BAA blood profiles in rats. As exposure continued, the rates of elimination for both 2BE and 2BAA decreased in both species, resulting in longer residence times in the blood. When 19-month-old naive mice were exposed to 125 ppm, 2BE was rapidly cleared from the systemic circulation, exhibiting clearance profiles similar to young mice. However, old mice eliminated 2BAA from blood > 10 times slower than young mice after 1-day of exposure. This delayed elimination of 2BAA in old mice was less obvious after 3 weeks of exposure, suggesting that there might be other factors in addition to the age of animals that could influence the apparent difference in 2BAA kinetics between old and young mice. It was concluded that the elimination kinetics of 2BE and 2BAA following repeated 2BE exposure appear to be dependent on species, sex, age, time of exposure, as well as the exposure concentration.

Administration, Inhalation↗
PubMed1998

Role of yeast Rth1 nuclease and its homologs in mutation avoidance, DNA repair, and DNA replication.

The RTH1(RAD27) gene of Saccharomyces cerevisiae encodes a structure-specific endonuclease that cleaves 5'-ended single-stranded DNA at its junction with duplex DNA. Genetic and biochemical studies have indicated a role of Rth1 nuclease in the removal of RNA primers formed during DNA replication. The rth1Delta mutation confers temperature-sensitive lethality, and increases sensitivity to alkylating agents. The instability of repetitive DNA is greatly enhanced in the rth1Delta mutant. The conditional lethality of the rth1Delta mutation indicates that another nuclease can function in DNA replication in the absence of RTH1. RAD2, a homolog of RTH1, is required for nucleotide-excision repair. Here, we examine three other homologs of RTH1/RAD2 - YEN1, EXO1, and DIN7. Deletion of any of these genes in the rth1Delta strain has no effect on cell viability, suggesting the involvement of another, and as yet unidentified, nuclease in the maturation of Okazaki fragments. Our data also indicate that only RTH1 functions in the repair of alkylation damage. Deletions of YEN1, EXO1, DIN7, or RAD2, either singly or when combined with one another and with the rth1Delta mutation, have no effect on the rate of instability of dinucleotide repeats or on the rate of formation of large duplications in the CAN1 gene. These data provide evidence of a high degree of specificity for the role of RTH1 in DNA replication and in base-excision repair, and for the requirement of RAD2 in nucleotide-excision repair. The possibility that both Rth1 and Exo1 function in DNA mismatch repair is discussed.

Alkylation↗
PubMed1998

Relationship of plasma buprenorphine and norbuprenorphine to withdrawal symptoms during dose induction, maintenance and withdrawal from sublingual buprenorphine.

AIMS: Examine the relationship between buprenorphine and norbuprenorphine plasma concentrations with subject-reported withdrawal symptomatology during buprenorphine dose induction, maintenance treatments (daily and alternate-day dosing) and withdrawal. DESIGN: Two groups of randomly assigned subjects inducted onto buprenorphine and maintained on 8 mg daily by the sublingual route for 18 days. Group 1 continued to receive daily buprenorphine to day 36. Group 2 subjects received alternate-day dosing of buprenorphine and placebo on days 19 to 36. Both groups received placebo on days 37 to 52. SETTING: Inpatient facilities at the Addiction Research Center, Intramural Research Center, NIDA, Baltimore, MD. PARTICIPANTS: Eleven male, heroin-dependent volunteers participating in a research study. INTERVENTION: Medications for treatment of withdrawal symptoms were prescribed as needed after day 39 (72 hours after the last dose of buprenorphine). MEASUREMENTS: Plasma concentrations of buprenorphine and norbuprenorphine, withdrawal symptomatology and pupil diameter. FINDINGS: The mean steady-state buprenorphine plasma concentration (24 hours) after daily administrations of sublingual buprenorphine for study days 21-35 was 0.80 ng/ml, and the mean alternate day steady-state buprenorphine plasma concentration (24 hours) was 0.77 ng/ml. Daily and alternate day steady-state norbuprenorphine plasma concentrations were 1.10 and 0.90 ng/ml, respectively. Predicted alternate day steady-state buprenorphine and norbuprenorphine plasma concentrations at 48 hours were 0.49 ng/ml and 0.57 ng/ml, respectively. Withdrawal scores varied inversely with plasma concentration. There were no significant differences between Groups 1 and 2 during steady-state (days 21-35) with regard to withdrawal scale scores or pupillary diameter. The overall, mean terminal elimination half-lives for buprenorphine and norbuprenorphine were 42 and 57 hours, respectively. CONCLUSIONS: during daily buprenorphine maintenance, plasma concentrations greater than 0.7 ng/ml of buprenorphine and norbuprenorphine were associated with minimal withdrawal symptoms. The long elimination half-life of buprenorphine suggested that increasing the buprenorphine dose with alternate-day administration may provide an effective, flexible therapy regimen for the treatment of opioid dependence.

Administration, Sublingual↗
PubMed1998

Laboratory testing for Neisseria gonorrhoeae by recently introduced nonculture tests: a performance review with clinical and public health considerations.

Since 1992 two new nucleic acid-based tests (Gen-Probe Pace 2 and Abbott LCR) for the diagnosis of Neisseria gonorrhoeae infection have been approved by the U.S. Food and Drug Administration. We systematically assessed the quality of 21 studies that evaluated these tests' performance compared with that of culture for diagnosis of gonorrhea, on the basis of established criteria. We estimated overall test sensitivity and specificity by the testing method, sex, and anatomic site. None of the studies optimally fulfilled all quality criteria; few studies adequately used reference tests or described blinding. The sensitivity and specificity of nucleic acid hybridization (approximately 85%, approximately 98%) and amplification tests (approximately 95%, approximately 99%) were high and did not appear to differ substantially by sex or anatomic site. When proficiency in the performance of culture is high, the new tests are comparable to culture and may not offer a substantial advantage; in settings where optimization of culture is difficult, nucleic acid amplification may detect more infections than nucleic acid probe or culture.

Bacteriological Techniques↗
PubMed1998

Prevalence variations in psychotropic treatment of children.

This study was undertaken to clarify several aspects of the estimation of prevalence of three commonly use pediatric psychotropic agents, namely, methylphenidate, desipramine, and imipramine. The study aims are threefold: (1) to show the variability of drug prevalence by comparing estimates from three data sources; (2) to show the misleading impression that can be created by reporting drug prevalence estimates based on counts of prescriptions rather than persons; (3) to show the utility of gender-by-age-specific prevalence of drug use as a marker for diagnosis. Two data sources that yield population-based prescription estimates were available: 1991 Medicaid administrative claims data for prescriptions from a mid-Atlantic state and 1991 prescription records of the northwest region of Kaiser Permanente, a staff-model health maintenance organization (HMO). Another source of data consists of the 1991 National Ambulatory Medical Care Survey, which records medication information reported during physician office visits. Data analysis consists of quantitative estimates of (1) drug prevalence from each source; (2) the ratio of prescription claims to persons; and (3) the proportion of drug use according to age and gender. Methylphenidate and desipramine prevalence had a twofold greater use among state Medicaid enrollees compared with HMO enrollees. Average claims-to-person ratios of 5:1 suggest better accuracy using persons with medication rather than prescription counts. Gender-by-age-specific prevalence rates showed that 75% of the drug use for desipramine among those less than 15 years old was found among males, whereas 75% of the desipramine use among those 15 or older was found among females, suggesting its use for the treatment of attention deficit-hyperactivity disorder among young males and for depression among older females. The variability of community physician decision making in pediatric psychopharmacology is better understood by observing drug prevalence rates from different settings. National sampling efforts should be undertaken to verify regional and setting-specific prevalence findings and to learn the reasons for their fluctuation.

Adult↗
PubMed1998

Recent patterns of hormone replacement therapy use in a large managed care organization.

Rates of hormone replacement therapy (HRT) in women have varied substantially over the last 25 years. Data on the impact of recent recommendations for widespread use to prevent cardiovascular disease and osteoporosis and factors that influence use are needed. We attempted to (1) describe recent trends in HRT use, (2) investigate the relationship between HRT use and prepaid drug benefit, and (3) detail prescribing frequencies by provider specialty. We conducted a cross-sectional analysis of annual HRT pharmacy dispensings from 1986 to 1995 in a large HMO to all female HMO members aged 45 years and older. HRT rates increased among all age categories, although the magnitude of change varied by age. Highest rates of use were found in those 50-59 years old. Although combined estrogen-progestin use increased, 57% of all estrogen users did not receive progestin in 1995. Unopposed estrogen use was largely limited to hysterectomized women. Women of all ages with no prepaid drug benefit as part of their HMO coverage had the lowest HRT rates. Internal medicine, obstetrics/gynecology, and family practice providers prescribed over 90% of HRT, and prescriber specialty varied with user age. HRT use increased in the HMO from 1986 to 1995, especially among younger women. In 1995, about half of women aged 50-64 years received one or more HRT dispensings. As the benefits, risks, and cost effectiveness of HRT depend on the duration of use, additional information on current use duration is needed. Combined estrogen-progestin use increased and appeared appropriate to hysterectomy status. Research is needed to determine if lower HRT use rates among women without a prepaid drug benefit indicate less prophylactic HRT use, particularly among younger women, for whom this lack of coverage was relatively common.

Age Factors↗
PubMed1998

Information about barriers to planned change: a randomized controlled trial involving continuing medical education lectures and commitment to change.

PURPOSE: To determine whether practicing physicians receiving only clinical information at a traditional continuing medical education (CME) lecture (control group) and physicians receiving clinical information plus information about barriers to behavioral change (study group) would alter their clinical behaviors at the same rate. METHOD: In a randomized controlled trial, the investigators matched 13 pairs of U.S. and Canadian medical schools, assigning one school from each pair to study or control conditions. Following the commitment-to-change model, the investigators asked the primary care physicians attending control or study lectures on the management of cardiovascular risks whether they intended to make behavioral changes as a result of participating in the lectures and, if so, to indicate the specific changes. Thirty to 45 days later, the investigators surveyed the responding physicians to learn whether they had implemented those changes. RESULTS: Information about barriers to change did not increase the likelihood that physicians in the study group would report successful changes; they were no more likely to change than those in the control group. However, the physicians in both study and control groups were significantly more likely to change (47% vs 7%, p < .001) if they indicated an intent to change immediately following the lecture. CONCLUSIONS: Successful change in practice may depend less on clinical and barriers information than on other factors that influence physicians' performances. To further develop the commitment-to-change strategy in measuring the effects of planned change, it is important to isolate and learn the powers of individual components of the strategy as well as their collective influence on physicians' clinical behaviors.

Behavior↗