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Biomedical subjects

R E Johnson

Publications and source records attributed to R E Johnson.

At least 55 records · Page 3Linked to original sources

Treatment of opioid-dependent pregnant women with buprenorphine.

AIMS: To assess the maternal and fetal acceptability of buprenorphine and neonatal abstinence syndrome (NAS) in children born to buprenorphine-maintained mothers. DESIGN AND SETTING: Open-label, flexible dosing, inpatient induction with outpatient maintenance, conducted at the University of Vienna within the existing pregnancy and drug addiction program. PARTICIPANTS: Fifteen opioid-dependent pregnant women. INTERVENTION: Sublingual buprenorphine tablets (1-10 mg/day). MEASUREMENTS: Mothers: withdrawal symptoms (Wang Scale), nicotine dependence (Fagerström Scale: FTQ) and urinalysis. Neonates: birth outcome and NAS (Finnegan Scale). FINDINGS: All subjects were opioid-, nicotine- and cannabis-dependent. Buprenorphine was well tolerated during induction (Wang Score < or = 4) and illicit opioid use was negligible (91% opioid-negative). All maternal, fetal and neonatal safety laboratory measures were within normal limits or not of clinical significance. Mean birth outcome measures including gestational age at delivery (39.6 +/- 1.5 weeks), Apgar scores (1 min = 8.9; 5 min = 9.9; and 10 min = 10), birth weight (3049 +/- 346 g), length (49.8 +/- 1.9 cm) and head circumference (34.1 +/- 1.8 cm) were within normal limits. The NAS was absent, mild (without treatment) and moderate (with treatment) in eight, four and three neonates, respectively. The mean duration of NAS was 1.1 days. CONCLUSIONS: Buprenorphine appears to be well accepted by mother and fetus, and associated with a low incidence of NAS. Further investigation of buprenorphine as a maintenance agent for opioid-dependent pregnant women is needed.

Buprenorphine↗

Localized pruritus: a presenting symptom of a spinal cord tumor in a child with features of neurofibromatosis.

Central nervous system (CNS) and spinal cord tumors are not uncommon in patients with neurofibromatosis (NF); however, it is impossible to select patients with NF who are at a particularly high risk. Localized pruritus may be a clue to the presence of a spinal cord or CNS tumor. This is the first report of an infant with features of NF, whose presenting symptom of a spinal cord tumor was localized symmetrical dermatomal itch. Moreover, we review the literature of localized pruritus in CNS and spinal cord tumors and peripheral nervous system conditions.

Abdomen↗

Evaluation of nucleic acid amplification tests as reference tests for Chlamydia trachomatis infections in asymptomatic men.

Urine ligase chain reaction (LCR) and PCR tests and urethral swab culture were compared for their abilities to detect Chlamydia trachomatis infection in 3,639 asymptomatic men by using one-, two-, and three-test reference standards. Frozen urine at four of five participating centers was also tested by a transcription-mediated amplification assay which was used as a reference test. LCR increased the yield of positive results by 27% and PCR increased the yield of positive results by 26% over the yield of positive results by culture (n = 295). LCR and PCR sensitivities were similar, ranging from 80.4 to 93.5%, depending on the reference standard. Culture sensitivity was substantially less. A multiple-test standard yielded LCR, PCR, and culture specificities of 99.6%, with or without discrepant analysis. Test performance varied among centers partly due to different interpretations of the testing protocols. The study confirms that urine LCR and PCR for the detection of C. trachomatis have substantially improved sensitivities over that of urethral swab culture for testing of asymptomatic men, enabling screening of this important target group. These tests, perhaps in combination, are also candidate reference tests for the conduct of test evaluation studies.

Animals↗

Evidence for the involvement of nucleotide excision repair in the removal of abasic sites in yeast.

In eukaryotes, DNA damage induced by ultraviolet light and other agents which distort the helix is removed by nucleotide excision repair (NER) in a fragment approximately 25 to 30 nucleotides long. In humans, a deficiency in NER causes xeroderma pigmentosum (XP), characterized by extreme sensitivity to sunlight and a high incidence of skin cancers. Abasic (AP) sites are formed in DNA as a result of spontaneous base loss and from the action of DNA glycosylases involved in base excision repair. In Saccharomyces cerevisiae, AP sites are removed via the action of two class II AP endonucleases, Apn1 and Apn2. Here, we provide evidence for the involvement of NER in the removal of AP sites and show that NER competes with Apn1 and Apn2 in this repair process. Inactivation of NER in the apn1Delta or apn1Delta apn2Delta strain enhances sensitivity to the monofunctional alkylating agent methyl methanesulfonate and leads to further impairment in the cellular ability to remove AP sites. A deficiency in the repair of AP sites may contribute to the internal cancers and progressive neurodegeneration that occur in XP patients.

Alkylating Agents↗

Sarcoidosis presenting as spiculated breast masses.

A 67-year-old woman sought medical treatment of cardiomyopathy, which had been diagnosed 2 years earlier; the causative factor was sarcoidosis. A screening mammogram revealed multiple spiculated masses in both breasts. A review of previous films obtained elsewhere showed that these masses had been increasing in prominence during the past 3 years. The patient had no visible axillary nodal abnormalities. Sarcoidosis was considered a diagnostic possibility, and a large-core needle biopsy was done with stereotactic guidance. The histological diagnosis was non-necrotizing granulomatous inflammation, consistent with sarcoidosis.

Aged↗

Fidelity and processivity of Saccharomyces cerevisiae DNA polymerase eta.

The yeast RAD30 gene functions in error-free replication of UV-damaged DNA, and RAD30 encodes a DNA polymerase, pol eta, that has the ability to efficiently and correctly replicate past a cis-syn-thymine-thymine dimer in template DNA. To better understand the role of pol eta in damage bypass, we examined its fidelity and processivity on nondamaged DNA templates. Steady-state kinetic analyses of deoxynucleotide incorporation indicate that pol eta has a low fidelity, misincorporating deoxynucleotides with a frequency of about 10(-2) to 10(-3). Also pol eta has a low processivity, incorporating only a few nucleotides before dissociating. We suggest that pol eta's low fidelity reflects a flexibility in its active site rendering it more tolerant of DNA damage, while its low processivity limits its activity to reduce errors.

DNA Damage↗

Requirement of yeast SGS1 and SRS2 genes for replication and transcription.

The SGS1 gene of the yeast Saccharomyces cerevisiae encodes a DNA helicase with homology to the human Bloom's syndrome gene BLM and the Werner's syndrome gene WRN. The SRS2 gene of yeast also encodes a DNA helicase. Simultaneous deletion of SGS1 and SRS2 is lethal in yeast. Here, using a conditional mutation of SGS1, it is shown that DNA replication and RNA polymerase I transcription are drastically inhibited in the srs2Delta sgs1-ts strain at the restrictive temperature. Thus, SGS1 and SRS2 function in DNA replication and RNA polymerase I transcription. These functions may contribute to the various defects observed in Werner's and Bloom's syndromes.

Bloom Syndrome↗

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↗

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↗

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↗

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↗

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↗

Akinesia and postural abnormality after unilateral dopamine depletion.

Following unilateral nigrostriatal dopamine depletion rats engage in drug-induced and spontaneous turning. These asymmetric behaviors are associated with a hemispheric asymmetry in the dopamine function. Several tests of 'spontaneous' behavior have revealed other abnormalities, primarily in posture and akinesia. A test is described here which quantifies postural abnormalities, as well as difficulties in initiating and terminating movement. This test may be suitable for evaluating aspects of dopamine-mediated behaviors not addressed by drug tests and may prove valuable in evaluating the potential of new treatment strategies for Parkinson's disease.

Animals↗

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↗

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↗

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↗