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Biomedical subjects

A Stevens

Publications and source records attributed to A Stevens.

At least 19 recordsLinked to original sources
PubMed1999

The Toll-like receptor 2 is recruited to macrophage phagosomes and discriminates between pathogens.

Macrophages orchestrate innate immunity by phagocytosing pathogens and coordinating inflammatory responses. Effective defence requires the host to discriminate between different pathogens. The specificity of innate immune recognition in Drosophila is mediated by the Toll family of receptors; Toll mediates anti-fungal responses, whereas 18-wheeler mediates anti-bacterial defence. A large number of Toll homologues have been identified in mammals, and Toll-like receptor 4 is critical in responses to Gram-negative bacteria. Here we show that Toll-like receptor 2 is recruited specifically to macrophage phagosomes containing yeast, and that a point mutation in the receptor abrogates inflammatory responses to yeast and Gram-positive bacteria, but not to Gram-negative bacteria. Thus, during the phagocytosis of pathogens, two classes of innate immune receptors cooperate to mediate host defence: phagocytic receptors, such as the mannose receptor, signal particle internalization, and the Toll-like receptors sample the contents of the vacuole and trigger an inflammatory response appropriate to defence against the specific organism.

Adaptor Proteins, Signal Transducing↗
PubMed1999

First-episode schizophrenics show normal duration and topography of quasistationary EEG segments as compared to controls, during rest as well as during active tasks.

In patients suffering from chronic schizophrenia, both altered temporospatial structure of the EEG and impaired activation during cognitive tasks have repeatedly been demonstrated. The present study evaluates whether similar abnormalities are present in drug-naive first-episode schizophrenics. The EEGs of 32 schizophrenic patients and of 52 healthy controls were recorded during a simple and a complicated motor task, a simple and a complicated auditory stimulus, and during resting periods between the tasks. The temporospatial characteristics were evaluated by adaptive segmentation of EEG, which decomposes an EEG into temporal segments of quasistationary activity. No differences in the temporal and topographic aspects of the EEGs were found between the first-episode schizophrenic patients and the controls, neither during the resting EEGs nor during active tasks. Moreover, the dynamic course of the EEGs, defined as the alternation between task-related changes of temporospatial patterns and the reappearance of resting patterns, was identical in patients and controls. The present findings suggest that while abnormal EEG power spectra seem a consistent finding in treated as well as in never-treated schizophrenics, altered temporospatial patterns and reduced task-related EEG changes are inconsistent signs.

Adult↗
PubMed1999

Monitoring mRNA decapping activity.

mRNA decapping is a common step shared between two important mRNA decay pathways in yeast, Saccharomyces cerevisiae. To investigate how mRNAs are decapped, we have developed an assay that can be easily used to measure the decapping activity. This assay has been used to isolate yeast strains with altered decapping activities. The results demonstrated that decreased decapping activity in vitro corresponds well with the decapping-deficient phenotype in vivo. This assay has been applied to the purified yeast decapping enzyme Dcp1 protein as well as crude yeast extracts and Xenopus oocyte extracts.

Animals↗
PubMed1999

The lack of associations between rheumatoid arthritis and both nulliparity and infertility.

OBJECTIVES: Rheumatoid arthritis (RA) is an autoimmune disease that occurs more commonly in women and frequently onsets in women of childbearing age. Pregnancy often causes disease remission, with a subsequent flare postpartum. Nulliparity may be a risk factor for RA, but the literature does not consistently report this finding. There may be a production of antibodies in women with RA that could lead to infertility, and subsequent nulliparity, but this has not been proved. We wanted to determine whether there was a relationship between nulliparity, infertility, oral contraceptive use, and adverse pregnancy outcome in women with newly diagnosed RA. METHODS: Through a case control study, using a mailed questionnaire, we compared the fertility and pregnancy outcome histories of 34 women between the ages of 19 and 44 years with recent-onset RA with 68 healthy controls matched for age and marital status. The response rate was 97%. A review of the literature also was performed to study the associations between RA and infertility and nulliparity, using Medline searching key references. RESULTS: We found no association between infertility and the onset of RA. Seventy-one percent of women with RA and 68% of controls had been pregnant. There was a trend toward increased nulliparity in these patients, but the result was not statistically significant (odds ratio [OR], 1.4; P<.6). There were no differences in the number of children (2.6 v. 2.7; P<.6) and parity outcomes in the two groups. Age at first pregnancy was younger in the women with RA (22.6 v. 25.5 years; P<.008), but the education level was higher in the controls (P<.0001), which may explain these differences. Oral contraceptive use was lower in the RA women, but more RA women had long-term use (greater than or equal to 5 years), and neither result was statistically significant. Literature review shows that at best, there are weak negative associations between current estrogen use and RA, and no association with nulliparity and infertility. CONCLUSIONS: It appears that infertility, the number of pregnancies, and pregnancy outcome are not strongly associated with the risk of developing RA in women of childbearing age. However, in this study there may have been selection biases in the women with RA and the controls that differentially could have affected their reproductive outcomes. Thus, a true association could have been missed. Most other published studies find no association between nulliparity and RA.

Adolescent↗
PubMed1999

Pilot study of televideo psychiatric assessments in an underserviced community.

OBJECTIVE: The goal of this study was to evaluate patient and physician acceptance of televideo interviews for general psychiatric assessments. METHOD: DSM-III-R diagnoses for axes I and II were made for 40 patients by using the Structured Clinical Interview for DSM-III-R. The patients were then randomly assigned to face-to-face or televideo interviews for general psychiatric assessments conducted by psychiatrists. After each interview the patient and psychiatrist completed measures evaluating perceived rapport and level of satisfaction with the interview. RESULTS: The patients gave high ratings to both satisfaction and ability to develop rapport for both the televideo and face-to-face interviews. The psychiatrists expressed significantly less satisfaction with the televideo interviews, but their actual ratings were positive. CONCLUSIONS: Despite geographic distance, televideo interviews allow a sense of connection between patient and psychiatrist. Lower-cost technology may increase the use of televideo to extend psychiatric service to geographically isolated communities.

Adolescent↗
PubMed1999

Axon repulsion from the midline of the Drosophila CNS requires slit function.

Guidance of axons towards or away from the midline of the central nervous system during Drosophila embryogenesis reflects a balance of attractive and repulsive cues originating from the midline. Here we demonstrate that Slit, a protein secreted by the midline glial cells provides a repulsive cue for the growth cones of axons and muscle cells. Embryos lacking slit function show a medial collapse of lateral axon tracts and ectopic midline crossing of ventral muscles. Transgene expression of slit in the midline restores axon patterning. Ectopic expression of slit inhibits formation of axon tracts at locations of high Slit production and misdirects axon tracts towards the midline. slit interacts genetically with roundabout, which encodes a putative receptor for growth cone repulsion.

Animals↗
PubMed1999

Work practices and histopathological changes in the tenosynovium and flexor retinaculum in carpal tunnel syndrome in women.

We studied 58 women of employable age with the carpal tunnel syndrome in order to determine whether the histological appearances of the carpal tunnel, tenosynovium and flexor retinaculum are influenced by work practices. Age, body mass index and the duration of symptoms did not correlate with the extent of oedema or fibrosis within the tenosynovium. The incidence of abnormality on histological examination of the tenosynovium was the same in employed and unemployed patients (p = 1.0), and was not influenced by the level of repetition (p = 0.89) or force (p = 0.29) of work. Myxoid degeneration within the flexor retinaculum was, however, more common in women undertaking 'high-force' work. Apart from this finding, the results suggest that work practices do not affect tenosynovial thickening, fibrosis or oedema in patients with carpal tunnel syndrome.

Adult↗
PubMed1999

A method for the standardized offline collection of exhaled nitric oxide.

STUDY OBJECTIVES: Exhaled nitric oxide (ENO) is a noninvasive marker of airway inflammation. The purpose of this study was to compare a standardized offline ENO measurement apparatus with a validated on-line method. DESIGN: Asthmatic volunteers (n = 21) had ENO measured by the two following methods: (1) inhalation to total lung capacity (TLC) followed by exhalation at a constant flow (45 mL/s) against a high resistance, while monitoring nitric oxide (NO) and pressure on-line; and (2) inhalation to TLC and exhalation into mylar balloons via an apparatus that included the same resistance and flow rate as used in the on-line method. We also examined NO stability in mylar balloons over 48 h. MEASUREMENTS AND RESULTS: ENO values (given as geometric mean in parts per billion [ppb]; 95% confidence intervals) differed between the on-line method (69.6; 42.6 to 113.8) and the offline method (49.5; 30.9 to 79.3), indicating that the offline method gave lower ENO measures than the on-line method (p < 0.001). Furthermore, this difference between measures increased with increasing mean values. The intraclass correlation coefficient (0.931), however, showed excellent correlation between the on-line and offline methods. Within-subject repeatability, as assessed by the coefficient of repeatability (CR), was good for both the on-line and offline methods (CR, 1.09 and 1.17, respectively). Geometric mean NO concentrations (95% confidence limits) in mylar balloons containing exhalate increased from a baseline of 55.8 ppb (36.9, 84.4) to 64.5 ppb (45.6, 91.1) and 69.5 ppb (51.4, 94.0) at 24 h and 48 h, respectively. CONCLUSIONS: The offline method gave reproducible ENO values that were consistently smaller than, but showed good correlation with, values obtained with on-line ENO collection. This method is suitable for offline collection, but the measured values are not interchangeable with those obtained by on-line measurement.

Airway Resistance↗
PubMed1999

Comparison of MMPI-A, Marks and Briggs, and MMPI-2 norms for juvenile delinquents.

A study was conducted to compare scores of juvenile delinquents on the new MMPI-A to previous research and to compare 3 sets of norms for adolescents: the MMPI-A, the Marks-Briggs adolescent norms, and the MMPI-2 adult norms. Subjects, 11 boys and 11 girls, were hospitalized adolescents, aged 14 to 17 years, with a history of conduct problems. Analysis of MMPI-A scale scores for boys indicated elevated T-score means on scales F (64), Hs (64), Pd (65), Pa (68), Pt (68), Sc (70), and Ma (66). Mean T scores for girls on the MMPI-A were elevated on scales of F (62), Pd (64), and Sc (62). The findings that the mean T score for scales Pd, Sc, and Ma are elevated for this population is consistent with previous research on juvenile delinquents. In general, the MMPI-A scale elevations were lowest, followed by the Marks-Briggs norms. The MMPI-2 T-score means were the most elevated. One of the limitations of the present investigation is an extremely small sample. Until further research is conducted on larger samples, clinicians concerned about the different norms are encouraged to plot MMPI-A scores on both adolescent and adult norms. It is also recommended that the MMPI-A be included as part of an assessment battery with other objective tests, clinical observation, and patient report.

Adolescent↗
PubMed1999

The false-negative fraction: a statistical method to measure the efficacy of cervical smear screening laboratories.

The false-negative fraction (FNF) is emerging as a statistical parameter that may be used to evaluate the efficacy of Papanicolaou smear screening laboratories. Our objectives for this paper are to acquaint non-laboratorians with this important measurement and to measure the FNF of the Air Force Cyto-center (AFCC) at the Armed Forces Institute of Pathology in Washington, DC. The FNF is defined as estimated false negatives divided by (true positives plus estimated false negatives). Most often, the number generated is multiplied by 100 and expressed as a percent. We have determined the FNF of the AFCC to be 3.7%. This value compares favorably with most others reported in the medical literature.

Aerospace Medicine↗
PubMed1998

Comparative analyses of the secondary structures of synthetic and intracellular yeast MFA2 mRNAs.

The overall folded (global) structure of mRNA may be critical to translation and turnover control mechanisms, but it has received little experimental attention. Presented here is a comparative analysis of the basic features of the global secondary structure of a synthetic mRNA and the same intracellular eukaryotic mRNA by dimethyl sulfate (DMS) structure probing. Synthetic MFA2 mRNA of Saccharomyces cerevisiae first was examined by using both enzymes and chemical reagents to determine single-stranded and hybridized regions; RNAs with and without a poly(A) tail were compared. A folding pattern was obtained with the aid of the MFOLD program package that identified the model that best satisfied the probing data. A long-range structural interaction involving the 5' and 3' untranslated regions and causing a juxtaposition of the ends of the RNA, was examined further by a useful technique involving oligo(dT)-cellulose chromatography and antisense oligonucleotides. DMS chemical probing of A and C nucleotides of intracellular MFA2 mRNA was then done. The modification data support a very similar intracellular structure. When low reactivity of A and C residues is found in the synthetic RNA, approximately 70% of the same sites are relatively more resistant to DMS modification in vivo. A slightly higher sensitivity to DMS is found in vivo for some of the A and C nucleotides predicted to be hybridized from the synthetic structural model. With this small mRNA, the translation process and mRNA-binding proteins do not block DMS modifications, and all A and C nucleotides are modified the same or more strongly than with the synthetic RNA.

Base Sequence↗
PubMed1998

Decreased duration and altered topography of electroencephalographic microstates in patients with panic disorder.

The topography and temporal sequence of scalp electrical fields were analyzed by adaptive segmentation of the continuous electroencephalogram (EEG) in 27 patients with panic disorder and 28 control subjects during rest phases and during the viewing of a neutral (mushroom) or an emotionally relevant (casualty) picture. The results indicate decreased duration of brain microstates in panic patients during all conditions. Comparison of the resting phases with the viewing conditions revealed a significant acceleration of EEG microstates in both the patients and the control subjects. Patients and control subjects differed in the topography of the fields during rest: control subjects showed a left-anterior/right-posterior orientation, while panic patients showed a predominantly right-anterior/left-posterior orientation. Neither group displayed any topographic changes when viewing the mushroom picture. However, when viewing the anxiety-specific casualty picture, panic patients shifted fields in a different way than did control subjects. Centroid topography does not permit clear localization of the cortical generators. It is concluded that panic patients show a generally increased cortical activation compared with healthy control subjects, and activate different neuronal arrays when viewing an anxiety-specific stimulus.

Adult↗
PubMed1998

Endonucleolytic cleavage of RNA at 5' endogenous stem structures by human flap endonuclease 1.

Structure-specific nucleases called 5' flap endonucleases cleave unannealed 5' arms of template-primer DNA model substrates at the start of the duplex and are involved in Okazaki fragment processing during DNA synthesis. To determine the possible use of the enzymes in RNA structure analysis, the cleavage of synthetic and native RNAs was examined using flap endonuclease 1 (Fen1) of HeLa cells. RNAs are cleaved at about 20% of the rate of DNA model substrates, and most of the cleavage sites are within 200 nucleotides of the 5' end. Hydrolysis of MFA2 mRNA of yeast shows that the cleavages are at the start of five possible stem structures of a folded secondary structure predicted on the basis of both chemical and enzymatic structure probing. 16S ribosomal RNA of Escherichia coli is cleaved at several 5' stem structures of its phylogenetically predicted folded structure. This type of RNA cleavage specificity may be very useful in secondary structure analysis in the future and also may be used by cells for specific 5' end-geared RNA cleavages.

Base Sequence↗