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Plasmid profiles compared with serotyping and pyocin typing for epidemiological surveillance of Pseudomonas aeruginosa.

The plasmid profiles of 112 clinical isolates of Pseudomonas aeruginosa were determined by two reproducible, rapid, plasmid screening methods. Plasmid DNA was present in 15% of isolates examined. Plasmids varied in size from 1.2 X 10(6) to 60.2 X 10(6) mol. wt. The dominant serotypes encountered were O:11 and O:4, which comprised 38% and 12% of strains, respectively. Four pyocin types (1, 10, 3 and 5) dominated (respective frequencies: 56, 15, 12 and 6%). Reproducibility of pyocin typing was distinctly inferior to both plasmid profiling and serotyping. Strains of identical serotypes could be further differentiated by dissimilar plasmid profiles. Serologically untypable or polyagglutinable strains were successfully characterised by plasmid profile patterns. Thus, plasmid profiling was shown to be a useful adjunct to serotyping for the epidemiological typing of P. aeruginosa.

Anti-Bacterial Agents↗

Plasmid profiles of Shigella dysenteriae type 1 isolates from Ethiopia with special reference to R-plasmids.

Plasmid profiles of 80 Shigella dysenteriae type 1 (Shiga's bacillus) strains, collected between 1974 and 1985 in Ethiopia, were examined. Strains with the dominant antibiotic-resistance (R-) type--resistance to ampicillin (A), chloramphenicol (C), streptomycin (S), sulphadiazine (Su) and tetracycline (T)--showed two distinct plasmid profiles (PP). Six plasmid bands were demonstrated in "Ethiopian strains" with PP-1A isolated between 1974 and 1982. In mating experiments with these strains, Escherichia coli K12 recipients showed plasmids pYH10a (72 Mda, atypical Inc FIme, coding for ACSSuT resistance). Eight plasmid bands were demonstrated in strains with PP-2A. These strains were first isolated in 1980 and carried plasmid pYH11a (40 Mda, Inc X, coding for ACT resistance). Strains with PP-2A were identical with a "Zairian strain" described elsewhere. Strains with R-type ACT were "Zairian strains" lacking the 5.1- and 4.2-Mda plasmids. Those with R-type CSSuT were temporally clustered in 1978-1980 and carried plasmid pYH12 (58 Mda, Inc B, coding for the same R-type). A trimethoprim-resistant strain (Gimira strain) had a pattern of small plasmids similar to those of the "Zairian strain" and is probably a subclone of the latter. The fact that a limited number of plasmid profiles have remained constant over many years shows the limitation of plasmid profile analysis as an epidemiological tool. However, when the usual profile is known for a given area, identification of a distinctly different pattern becomes easy and epidemiologically useful.

DNA Replication↗

Granular dynamics of density profiles in a suspension interface.

The temporal evolution of the density profiles at the interface of a Rayleigh-Taylor instability in a sedimenting suspension is experimentally investigated. It is found that the sand-glycerin density gradients within the interface change with time, and that the evolution of the gradients differs significantly, depending on the location: The density profiles become steeper in the regions where the suspension flows downwards, whereas the profiles become flatter in the regions where the fluid flows upwards. This observation shows that there is a motion of the sand grains relative to the carrier fluid and hence reveals the prevailing granular dynamics in the suspension interface. It shows a behavior of the suspension which is different from the behavior of a homogeneous Newtonian one-component fluid whose density profiles do not change in time. Another interesting result is that the slopes of the profiles differ already at the very beginning (t=0) of the evolution of the instability, indicating that the suspension might have self-structured prior to instability onset.

Journal Article↗

Metabolic profiling allows comprehensive phenotyping of genetically or environmentally modified plant systems.

Metabolic profiling using gas chromatography-mass spectrometry technologies is a technique whose potential in the field of functional genomics is largely untapped. To demonstrate the general usefulness of this technique, we applied to diverse plant genotypes a recently developed profiling protocol that allows detection of a wide range of hydrophilic metabolites within a single chromatographic run. For this purpose, we chose four independent potato genotypes characterized by modifications in sucrose metabolism. Using data-mining tools, including hierarchical cluster analysis and principle component analysis, we were able to assign clusters to the individual plant systems and to determine relative distances between these clusters. Extraction analysis allowed identification of the most important components of these clusters. Furthermore, correlation analysis revealed close linkages between a broad spectrum of metabolites. In a second, complementary approach, we subjected wild-type potato tissue to environmental manipulations. The metabolic profiles from these experiments were compared with the data sets obtained for the transgenic systems, thus illustrating the potential of metabolic profiling in assessing how a genetic modification can be phenocopied by environmental conditions. In summary, these data demonstrate the use of metabolic profiling in conjunction with data-mining tools as a technique for the comprehensive characterization of a plant genotype.

Cluster Analysis↗

Feature extraction and quantification of the variability of dynamic performance profiles due to the different sagittal lift characteristics.

Investigation of manual material handling (MMH) tasks, such as lifting, requires the quantification of the various kinematic and kinetic parameters of performance for assessment of the functional capacity and/or task demand profiles. Traditional statistical descriptive analyses usually involve computing the summary statistics (maximum, minimum, mean, and/or range) of the resulting performance parameters over the cycle duration (i.e., lifting/lowering cycle). Consequently, the significant information content of the time-varying signals is diminished, limiting the sensitivity of subsequent hypothesis testing procedures. The present study developed a methodology for representing and quantifying performance data variability of the kinematic and kinetic motion profiles due to the different lift characteristics (load, mode, and speed) during MMH tasks while capturing the temporal characteristics. Using a database of motion profiles from a manual lifting experiment, the Karhunen-Loeve Expansion (KLE) feature extraction technique was shown to be quite effective for representing the various motion profiles. The number of basis vectors (eigenvectors) and corresponding coefficients needed for accurate representation were substantially smaller than the original data set, resulting in data compression. Moreover, the effects of lift characteristics were investigated using analysis of variance techniques that recognize the vectorial constitution of the waveforms. The application of these techniques will enable the quantification of highly phasic profiles and enhance the ability to document the effect of intervening measures such as educational or physical training/exercise on the kinematic and kinetic patterns of performance. Additionally, the differential influence of lift characteristics on the variability of performance during different phases of lifting and lowering provides added resolution in the analysis of MMH tasks.

Adult↗

Pharmaco-EEG profiles of antidepressants. Pharmacodynamic studies with fluvoxamine.

1 Antidepressant drugs produce significant changes in human brain function as reflected in the quantitatively analysed EEG. Two main types of pharmaco-EEG profiles may be differentiated: a thymeretic (desipramine-like) profile characterised mainly by an alpha increase suggesting activating properties and a thymoleptic (imipramine- or amitriptyline-like) profile showing a concomitant increase of slow and fast activities and a decrease in alpha activity indicating also sedative qualities. A small number of compounds exhibit still different profiles. 2 Aside from determining the type of EEG changes, the pharmaco-EEG method seems to be of value in determining time and dose efficacy relations at the target organ, the human brain. Moreover, the relationships between pharmacodynamics and pharmacokinetics may be determined. 3 Fluvoxamine, a selective 5-hydroxytryptamine (5-HT) re-uptake inhibitor from the new class of 2-aminoethyloximethers of aralkylketones, produced a typical thymoleptic pharmaco-EEG profile after oral doses of 75 mg in a double-blind placebo-controlled study involving 10 healthy volunteers. Fluvoxamine (75 mg) induced less augmentation of slow activity than 75 mg imipramine, indicating less sedative properties of fluvoxamine than imipramine. 4 After 75 mg fluvoxamine psychometric tests demonstrated a tendency towards an improvement in attention, concentration, psychomotor activity, after-effect and mood and a significant increase in critical flicker fusion frequency as compared with placebo. Comparison with the reference drug, 75 mg imipramine, revealed a significant superiority of fluvoxamine regarding concentration, psychomotor activity, tapping, reaction time, mood and affectivity. 5 Side-effects (mostly tiredness) were seen in five out of 10 subjects after 75 mg fluvoxamine and in eight out of 10 subjects after 75 mg imipramine. There were no clinically relevant changes in pulse, systolic and diastolic blood pressure.

Adult↗

Transcriptional profiles in melanocytes from clinically unaffected skin distinguish the neoplastic growth pattern in patients with melanoma.

BACKGROUND: It is generally accepted that sunlight may contribute to the development of melanoma. OBJECTIVES: To analyse gene expression of melanocytes obtained from clinically unaffected skin of patients with melanoma and healthy controls before and after exposure to ultraviolet B radiation. METHODS: Using GeneChip array technology, the gene expression of melanocytes obtained from the two donor groups was profiled, in order to identify transcriptional differences affecting susceptibility to melanoma. RESULTS: The data collected did not show any difference between the expression profiles of melanocytes purified from normal donors and from patients with melanoma that was able to give a statistically significant class separation. However, by means of unsupervised clustering our data could be divided into two main classes. The first class included the transcriptome profiles of melanocytes obtained from skin samples of patients with a vertical growth phase (VGP) melanoma, while the second class included the transcriptome profiles of melanocytes obtained from skin samples of patients with a radial growth phase (RGP) melanoma. CONCLUSIONS: These data suggest that melanocytes in patients with VGP and RGP melanomas show significant differences in gene expression profiles, which allow us to classify patients with melanoma also from clinically unaffected skin.

Adult↗

Comparison of clinical and pharmacokinetic profiles of etanercept 25 mg twice weekly and 50 mg once weekly in patients with psoriasis.

BACKGROUND: Etanercept is a tumour necrosis factor antagonist that is approved in the U.S.A., Canada and Europe for treating adult patients with chronic moderate to severe plaque psoriasis. OBJECTIVES: To assess whether clinical efficacy, safety and pharmacokinetic (PK) profiles of etanercept 50 mg once weekly are comparable to etanercept 25 mg twice weekly. METHODS: Patients from a U.S. phase 3 study and a global phase 3 study were subsequently enrolled in an open-label extension study (extension study) where they all received etanercept at a dose of 50 mg once weekly for an initial 12 weeks. Patients who had received at least 24 weeks of etanercept 25 mg twice weekly in the global phase 3 study and were enrolled in the extension study (n = 265) were assessed for efficacy and safety at extension study baseline and after 12 weeks of etanercept 50 mg once weekly. Efficacy endpoints included the Psoriasis Area and Severity Index (PASI), the Dermatology Life Quality Index and the Physician's Global Assessment of psoriasis. In addition, PK profiles from patients in the U.S. phase 3 study were compared with PK profiles from another set of patients in the extension study. Comparison was made between a subset of patients receiving etanercept 25 mg twice weekly dosing in the U.S. phase 3 study (n = 13) and those receiving etanercept 50 mg once weekly in the extension study (n = 84). RESULTS: The mean PASI score was 5.77 at extension study baseline after treatment with etanercept 25 mg twice weekly, which was sustained at 5.82 after 12 weeks of etanercept 50 mg once weekly. Similar results were observed in other efficacy endpoints. Etanercept 50 mg once weekly was generally well tolerated. No new safety findings were reported. PK profiles overlapped extensively between the two dosing regimens. CONCLUSIONS: In this report, we demonstrate that efficacy, safety and PK profiles were comparable between etanercept 25 mg twice weekly and 50 mg once weekly in patients who had received at least 24 weeks of etanercept 25 mg twice weekly prior to receiving etanercept 50 mg once weekly in the extension study.

Adult↗

Characteristics and profile of boys and girls with emotional and behavioural disorders in Flanders mental health institutes: a quantitative study.

BACKGROUND: In this article, we search for gender differences and outline a detailed gender profile for children and youngsters with emotional and behavioural disorders who are placed in Flemish residential care institutes. METHODS: Data were collected of all placements (517 children) in six residential and semi-residential mental health care centres for children and youngsters with emotional and behavioural disorders in East Flanders, Belgium. File data (gender, age, retention, current treatment, type of referral, education, intelligence, Diagnostic and Statistical Manual IV-diagnoses and medication use) were gathered. The Child Behaviour Check List (CBCL) was implemented and completed for each child. On the basis of the CBCL, a behaviour profile was developed by means of correlation tables (Pearson correlation coefficient) and cross tabulations. Finally, the profile was compared with the file data of the boys and the girls. RESULTS: Significant gender differences were found for type of referral, intelligence and diagnoses. The same profile was developed for both genders separately, based on variables Externalizing and Social Problems. The file data associated with the profile groups differ for boys and girls. CONCLUSIONS: The results of our study show the complexity and diversity of the needs of boys and girls with disruptive behaviour in Flemish residential care institutes. Flemish government has to be aware of the fact that the current referral system selects the children with outspoken externalizing and problematic behaviour towards special health care and special schools. They are relegated because the mainstream system is not equipped well enough to cope with their disruptive, aggressive behaviour. Even if governments are in favour of inclusive education, it seems that in practice a rest group is created, in which girls are selected through the same mechanisms as boys, in this case for the same reasons of negative externalizing behaviour and social problems. For this it seems appropriate that school and (semi)-residential institutes apply a specific and adapted methodology.

Adolescent↗

Analysis of plasmid profiling as a method for rapid differentiation of food-associated Clostridium perfringens strains.

Plasmid analysis of over 120 strains of Clostridium perfringens, isolated during food-poisoning incidents and from animal carcasses and food constituents with no association with food poisoning, showed the potential of plasmid profiling as a means of differentiating epidemiologically related strains. On average 65% of freshly isolated strains contained one or more plasmids which could be used in the analysis. Comparison of profiles of strains from unrelated sources or unrelated strains from the same source showed a particularly wide variety of plasmid profiles. Thus the possibility that epidemiologically-unrelated strains might possess similar profiles appears to be very low in this organism. Analysis of serologically-related strains from the same source revealed similar plasmid profiles in all the plasmid-bearing strains examined. A high proportion (71%) of fresh and well-characterized food-poisoning strains possessed plasmids of 6.2 kb in size (compared with 19% of non-food-poisoning strains). The possible role of these plasmids is discussed, since the structural gene encoding the enterotoxin type A was not present on any of the plasmids in the food-poisoning strains tested.

Animals↗

Fragile-X and Down's syndrome: are there syndrome-specific cognitive profiles at low IQ levels?

Individuals with either fragile-X syndrome or Down's syndrome with IQ scores less than 40 were assessed on the Down Syndrome Mental Status Exam. The results of the testing were examined for syndrome-specific cognitive profiles. No evidence for syndrome-specific cognitive profiles were found. These same individuals were then classified as high or low IQ, and each group was examined for IQ-level-specific profiles. Unique IQ level cognitive profiles were found. Classifying the individuals with regard to aetiology obscured IQ-level-specific strengths and weaknesses. Researchers and developers of curricula are cautioned against generalizing cognitive profiles to all IQ levels of a specific genetic syndrome.

Activities of Daily Living↗

Are caregivers' reports of motivation valid? Reliability and validity of the Reiss Profile MR/DD.

BACKGROUND: Sensitivity theory proposes that there are wide individual differences in what motivates people with intellectual disability. The Reiss Profile MR/DD is a rating scale that measures 15 fundamental motives. This study examined the internal consistency and interrater reliability of the 15 subscales as well as the validity of motivational profiles. METHOD: The study consisted of two distinct but related steps. First, the interrater reliability of the rating scale was established by having pairs of raters evaluate 48 individuals. Second, raters were presented with three different motivational profiles and asked to identify which one corresponded to the individual they had rated 4 weeks earlier. RESULTS: Results indicated good internal consistency (average alpha=0.84), significant variability in the interrater reliability (average intraclass correlation coefficient=0.52), and excellent validity (95% of the correct profiles were chosen). Average discrepancies between pairs of raters are presented. CONCLUSIONS: Interrater reliability is an important topic for professionals working in the field of intellectual disability and results are discussed in terms of the factors that affect it. This is the first published study to report on the interrater reliability of the Reiss Profile MR/DD.

Adaptation, Psychological↗

Influence of obstructive sleep apnoea on circadian blood pressure profile.

A high prevalence of systemic hypertension in obstructive sleep apnoea (OSA) has been described but data on circadian blood pressure (BP) profile are limited and give inconsistent results. The present study examines 24-h BP in 106 patients referred because of loud snoring or excessive daytime sleepiness in combination with snoring. Patients were classified as OSA (n = 62) or habitual snorers (HS) (n = 44). Respiratory disturbance index (RDI) in OSA was 47 + 24 vs. 2 +/- 2 in HS. Mean age and body mass index in OSA was significantly higher. BP was measured non-invasively at 15-min intervals during a 24-h period. Daytime and night-time BP was higher in OSA compared to HS. BP night/day ratio in OSA was 0.92 +/- 0.07 vs. 0.86 + 0.06 in HS (P < 0.05). To investigate the influence of variables other than breathing abnormalities during sleep on our results we compared BP profiles of 25 OSA and 25 HS matched for sex, age and body weight. Again differences in daytime and night-time BP and BP night/day ratio were significant. Using a value of at least 10% fall in nocturnal BP to describe a regular BP profile (dipper) 68% of OSA were classified as non-dippers vs. 24% of HS. Influence of short-term (2-4 days) nCPAP therapy on circadian BP profile was investigated in 34 patients with OSA. Systolic and diastolic nocturnal (but not daytime) BP was significantly reduced. The percentage of non-dippers was 79% before and 50% after treatment. In conclusion results of this study indicate a causal link between OSA and abnormal circadian BP profile.

Journal Article↗

Extended coagulation profiles of healthy baboons and of baboons rejecting GT-KO pig heart grafts.

INTRODUCTION: Derangements of coagulation, e.g. thrombotic microangiopathy (TM) and disseminated intravascular coagulation (DIC), limit the success of pig-to-baboon organ transplantation. Studies have investigated the coagulation profile in baboons post-xenotransplantation (XTx), but an extended coagulation profile of healthy baboons pre-XTx has not been reported. METHODS: Blood was drawn from nine healthy male baboons (approximate age 5 yr, mean weight 15 kg) that had not undergone any prior surgical or therapeutic procedures. An extended coagulation profile, consisting of markers of thrombin activation, fibrinolysis, endothelial activation, the protein C pathway, and overall reactive state, was investigated by a reference coagulation laboratory, using tests for human plasma. The mean value +/- SD was calculated for 18 parameters (analytes); values outside of the mean +/- 2 SD were excluded. Three baboons subsequently underwent transplantation with hearts from GT-KO pigs, and received either no therapy (B24603), CVF (B25003), or CVF + leflunomide (B24903), and their extended coagulation parameters were followed. RESULTS: For 14 of the 18 analytes, the human reference range reflected the coagulation status of healthy baboons. Exceptions included thrombin/antithrombin complex and fibrinopeptide A, which were elevated compared with the human reference range, while plasminogen activity was lower. The human assay failed to detect baboon plasminogen activator inhibitor-1. Immediately after GT-KO pig heart transplantation, the untreated B24603 demonstrated a coagulation profile consistent with its postoperative clinical status; DIC was not apparent, and the heart was electively excised within 2.5 h. In B25003 and B24903, that rejected their grafts on days 8 and 12, respectively, the coagulation profile showed evidence of DIC, particularly in B24903, which was clinically coagulopathic by this time. CONCLUSIONS: (i) The human reference range of extended coagulation parameters forms a basis for studies in baboons, with a few exceptions. (ii) Antibody-mediated rejection of GT-KO pig hearts in baboons can be associated with laboratory and clinical evidence of DIC.

Animals↗

Muscarinic receptor profiles of mouse brain astrocytes in culture vary with their tissue of origin but differ from those of neurons.

The two main cell populations in brain tissues are neurons and astrocytes. Cultures of both bear muscarinic acetylcholine receptors (mAChRs). Available data indicate that astrocyte mACRs are heterogeneous, but the particular subtypes on these cells are not known, nor is there any information as to whether there is a regional variation in the mAChR profile of astrocytes. This paper describes the mAChR profiles of cultured astrocytes derived from the cerebral hemispheres, mesencephalon and medulla-pons, and is a continuation of our study on cultures of neurons from these same tissues. Pharmacological studies showed that astrocytes accumulated small amounts of mAChRs with distinct pharmacological profiles which, for a given area, differed from those of neurons in culture. Northern blot analyses showed transcripts for m1 and m3 mAChRs only. Their concentrations differed from one cell population to another. Astrocyte cultures from the mesencephalon contained m1 mRNA amounts close to those in the tissue. Thus, at least part of the mAChR profile in vitro might be a true reflection of the cell's properties in vivo. Functional studies showed that mAChRs mediate the stimulation of phosphoinositide turnover in all three astrocyte cultures, that the amplitude of this response varies greatly with the origin of the cell, and that two pharmacological subclasses, M1 and M1-2-, are involved in these responses, but to different extents. Thus the CNS contains discrete astrocyte populations which in culture differ in their mAChR profiles at the molecular, the pharmacological and the functional levels.

Animals↗

The relation between daily salivary progesterone profile and endometrial development in the luteal phase of fertile and infertile women.

This study analysed the relation between daily salivary progesterone profiles in the luteal phase and endometrial development as assessed by morphometric studies of endometrial biopsies that were timed by luteinizing hormone surge. Among 34 fertile women studied, a threshold relation was noted between cumulative salivary progesterone concentration and 11 of the 17 morphometric features measured, as well as the results of the histological dating. Above the observed threshold, a significant linear correlation was found between cumulative salivary progesterone and the results of histological dating. Among 55 women, progesterone profile in the first half of the luteal phase, but not the second half, was found to be significantly lower in those with retarded endometrial development than in those with normal development. Overall, 50% of retarded endometrial development was associated with a subnormal progesterone profile, but the other 50% was associated with a normal progesterone profile, in keeping with an abnormal response of the endometrium due to progesterone receptor deficiency. Retarded endometrial development was more likely to be associated with a subnormal progesterone profile in the first half of the luteal phase than in the second half.

Adult↗

Prediction of fetal acidaemia in intrauterine growth retardation: comparison of quantified fetal activity with biophysical profile score.

OBJECTIVE: To study the relation between quantified fetal movements and fetal activity assessed by the biophysical profile score and the pH in umbilical arterial blood at elective caesarean section. DESIGN: Fetal activity was assessed within 24 h prior to caesarean section for decelerative fetal heart rate patterns both by quantification (% of time spent moving) and by applying the biophysical profile score (BPS) criteria. SETTING: Department of Obstetrics, University Hospital. SUBJECTS: Nineteen growth retarded fetuses. MAIN OUTCOME MEASURES: Fetal generalised movements (FGM%), fetal breathing movements (FBM%), total fetal activity (TFA% = FGM% + FBM%); FGM, FBM and tone as assessed according the biophysical profile score (BPS); umbilical arterial pH. RESULTS: In all 11 acidaemic fetuses (pH < 7.20) TFA% was below the 10th centile for normal fetuses; nine had decreased FGM% and eight decreased FBM%. Absence of FGM or tone according to the biophysical profile score was only seen in two acidaemic fetuses. CONCLUSION: TFA% < 11.7% was a better predictor of acidaemia at birth than either reduced FGM%, FBM%, or absence of FGM, FBM and tone as defined in the biophysical profile score. The two methods of assessing FBM were identical in predicting acidaemia, suggesting that in presence of acidaemia the decrease of FBM may be an all-or-none phenomenon. Furthermore, the data indicate that reduction in body movements may precede reduction in breathing movements.

Acidosis↗

Urine protein profiling with surface-enhanced laser-desorption/ionization time-of-flight mass spectrometry.

BACKGROUND: In the last few years there has been an increasing interest in exploring the human proteome. In particular, efforts have focused on developing strategies to generate reproducible protein maps of normal cells, tissues, and biologic fluids, from which studies can then compare protein expression between different groups (e.g., healthy individuals vs. those with a specific pathologic state). METHODS: Various extrinsic factors (instrument settings, matrix composition, urine storage post void, freeze-thaw cycles) and intrinsic factors (blood in urine, urine dilution, first-void vs. midstream urine) were analyzed with respect to their impact on urine protein profiling using surface-enhanced laser-desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). RESULTS: Extrinsic factors that critically influenced reproducibility and peak detection of urine protein profiling were matrix composition and instrument settings, while freeze-thaw cycles had minimal impact. Midstream urines samples did not undergo changes in their protein profile when stored for three days at 4 degrees C. Intrinsic factors that influenced normal urine protein profiling were blood in the urine and urine dilution. Female first-void urine had a significantly different ratio of proteins present compared to a midstream urine sample. Limitations of the SELDI-TOF-MS technique included ion suppression and quantification of individual proteins when protein composition was complex. CONCLUSION: SELDI-TOF-MS offers a unique platform for high throughput urine protein profiling; however, standardization of analysis conditions is critical, and both extrinsic and intrinsic factors must be taken into account for accurate data interpretation.

Female↗