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Inconsistencies between cytokine profiles, antibody responses, and respiratory hyperresponsiveness following dermal exposure to isocyanates.

Cytokine profiling of local lymph node responses has been proposed as a simple test to identify chemicals, such as low molecular weight diisocyanates, that pose a significant risk of occupational asthma. Previously, we reported cytokine messenger RNA (mRNA) profiles for dinitrochlorobenzene (DNCB) and six isocyanates: toluene diisocyanate, diphenylmethane-4,4'-diisocyanate, dicyclohexylmethane-4,4'-diisocyanate, isophorone diisocyanate, p-tolyl(mono)isocyanate, and meta-tetramethylene xylene diisocyanate. The present study was conducted to test the hypothesis that relative differences in the cytokine profile are predictive of relative differences in total serum immunoglobulin (Ig) E and respiratory responses to methacholine (Mch) following dermal exposure to the chemicals. After a preliminary experiment to determine an exposure regimen sufficient to achieve responses to Mch following dermal diisocyanate exposure, BALB/c mice received nine dermal exposures over a period of 28 days to one of six isocyanates, DNCB, or vehicle. Mice were then challenged with increasing doses of Mch and responsiveness was assessed using whole-body plethysmography. Serum antibody responses and cytokine mRNA profiles in the draining lymph node were also assessed. In separate experiments, cytokine protein assays were performed after five dermal exposures over a 14-day period. The response pattern for interleukin (IL)-4, IL-10, and IL-13 for the different isocyanates was highly reproducible as determined by RNAse protection assay, reverse transcription-PCR, or cytokine protein levels. However, the relative differences in T-helper cytokine profiles were not predictive of relative differences in either total serum IgE or respiratory responses to Mch following dermal exposure. The data suggest that the cytokine profiling approach needs to be further developed and refined before adoption and that other approaches to hazard identification should be pursued as well. Based on the weight of evidence from all the assays performed, it appears that all six isocyanates tested have some potential to cause respiratory hypersensitivity following dermal exposure.

Administration, Cutaneous↗

Cancer cell line identification by short tandem repeat profiling: power and limitations.

Cancer cell lines are used worldwide in biological research, and data interpretation depends on unambiguous attribution of the respective cell line to its original source. Short-tandem-repeat (STR) profiling (DNA fingerprinting) is the method of choice for this purpose; however, the genetic stability of cell lines under various experimental conditions is not well defined. We tested the effect of long-term culture, subcloning, and generation of drug-resistant subclones on fingerprinting profiles in four widely used leukemia cell lines. The DNA fingerprinting profile remained unaltered in two of them (U937 and K562) throughout 12 months in culture, and the vast majority of subclones derived therefrom by limiting dilution after long-term culture revealed the same profile, indicating a high degree of stability and clonotypic homogeneity. In contrast, two other cell lines (CCRF-CEM and Jurkat) showed marked alterations in DNA fingerprinting profiles during long-term culture. Limiting dilution subcloning revealed extensive clonotypic heterogeneity with subclones differing in up to eight STR loci from the parental culture. Similar heterogeneity was observed in subclones generated by selection culture for drug resistance where DNA fingerprinting proved useful in identifying possible resistance mechanisms. Thus, common tissue culture procedures may dramatically affect the fingerprinting profile of certain cell lines and thus render definition of their origin difficult.

Apoptosis↗

Recovery of heart rate variability profile in patients after coronary artery surgery.

UNLABELLED: We examined the different characteristics of heart rate variability (HRV) to define the time course of HRV profile after coronary artery surgery (CAS). Spectral analysis of HRV was performed on a 512-s segment of R-R intervals of the electrocardiogram on the preoperative day and on Postoperative Days 1, 2, 3, 4, 5, 6, 7, 14, 21, and 28. Power spectral area was divided into low (0.04-0.15 Hz; LF)- and high (0.15-0.5 Hz; HF)-frequency components. Fractal slope and sympathovagal slope of 1/f characteristics of HRV were determined in two different frequency ranges (from 0.01 to 0.15 Hz and from 0.01 to 0.5 Hz, respectively). Three recovery profiles of HRV were identified. Early HRV recovery profiles (Postoperative Days 1-6) included reduction in LF, HF, and sympathovagal slope, as well as an increase in fractal slope. Subsequent HRV recovery profiles (Postoperative Days 7-21) revealed reductions in LF, HF, and sympathovagal slope. Fractal slope became normal. Later HRV recovery profiles (Postoperative Day 28) demonstrated that all spectral components of HRV remained reduced, but sympathovagal and fractal slopes became normal. These changes in the HRV profile after CAS suggest significant postoperative alterations in cardiovascular homeostasis with significant but incomplete recovery during the first 28 postoperative days. IMPLICATIONS: Heart rate variability reflects normal neural regulation of cardiac function. This variability remains depressed as long as 28 days after coronary artery bypass surgery, but can recover as early as 1 wk postoperatively. Despite implied loss of normal neural regulation of cardiac function, a specific correlation between depressed heart rate variability and outcomes was not performed.

Adult↗

Relationship between MMPI-2 cluster profiles and surgical outcome in low-back pain patients.

The purpose of this study was to investigate back surgery outcome differences based on Minnesota Multiphasic Personality Inventory-2 (MMPI-2) profile types. Four homogenous subgroups were found from a hierarchical cluster analysis of 201 MMPI-2 profiles. These four clusters consisted of a Depressed-pathological profile, a conversion V profile (V-type), a neurotic Triad profile, and a within normal limit (WNL) profile. Patients in the WNL and Triad subgroups reported significantly more satisfaction with postsurgical improvement than did patients in the Depressed-pathological or V-type subgroups. The Triad subgroup also gave a more favorable subjective rating of surgical outcome than did patients in the Depressed-pathological or V-type subgroups. These groups also differed on measures of work status and nonwork-related physical activity levels but not on indices of pain.

Adult↗

The uncertainty in the activity estimate from a lung count due to the variability in chest wall thickness profile.

Calibration of a lung counter requires the use of a realistic torso phantom. The depth profile of both torso phantoms' (LLNL and JAERI) chest plate covers is fixed and assumed to be equivalent to a person's chest wall; however, ultrasound measurements of humans have shown this to be an approximation. When the depth profile of a calibration phantom is different from that of a subject, then a systematic uncertainty will be introduced into the activity estimate. Monte Carlo simulation has shown that changes in the depth profile of the chest wall thickness affect the counting efficiency. Ultrasound measurements have suggested that the coefficient of variation in the depth profile of the chest wall thickness lies between 13% and 26% for male workers; therefore, the added uncertainty to an activity estimate will be an over or underestimate of about a factor of 1.07 resulting from the different depth profile. The factor will be somewhat higher for females, probably about 1.2 at the extreme. These additional uncertainties resulting from depth profile differences are small compared with other uncertainties commonly encountered in lung counting: detector positioning, deposition patterns of the activity, measurement of the chest wall thickness, etc.

Computer Simulation↗

Searching for an assessment instrument to determine temporomandibular disorder pain profiles for the purposes of primary health care.

The objective was to study the utility of the graded chronic pain (GCP) scale of the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) for the purpose of recognizing TMD pain profiles in primary health care. The GCP scale was used to gather data from 93 consecutive TMD patients seeking treatment in a primary health care setting. The GCP data were compared with pain profiles assessed by scales similar to the more complicated multidimensional pain inventory (MPI). The scales used were able to produce the similar 'dysfunctional profiles' in the TMD patients as the original MPI scale in the sample of chronic pain patients. Also, the original MPI profiles of 'adaptive copers' and 'interpersonally distressed' were produced with distinctive features. The GCP grades distributed almost identically among the subgroups produced by the pain profiles. Most grade I patients were classified as adaptive copers (82--86%), most grade II patients were interpersonally distressed (59%) and all except one of the grade III patients were classified as dysfunctional (83%). The results seem to support the main assumption of our study that the GCP scale is a simple screening tool suitable for identifying primary care TMD patients with various types of pain profiles.

Adaptation, Psychological↗

Ambulatory care groups and the profiling of primary care physician resource use: examining the application of case mix adjustments.

A variety of profiling models and tools is utilized by payers, providers, and regulators to evaluate physician work, performance, and resource utilization. In physician profiling, the provider's pattern of practice is expressed as a rate of service or outcome. The article by Tucker, Weiner, Honigfeld, and Parton (this issue) compares the practice-based norms of primary care physicians by adjusting for case mix using ambulatory care groups (ACGs), a population-based classification method. Once the case mix is adjusted, the actual use of resources, as measured by overall charges, is compared with the expected value of resource use. In the Center for Research in Ambulatory Health Care Administration (CRAHCA) Physician Profiling Project, funded by The Robert Wood Johnson Foundation, physicians learn which services other physicians in their specialties perform. Physicians are able to compare their profiles with state and national level medians. The profiling project is one of the first demonstration projects in the field to profile ambulatory care practice patterns and collect patient demographics. An aspect of the project is to test the ACG classification system to data selected from 130 nonacademic practices representing over 5,000 physicians.

Ambulatory Care↗

The impact of practicing in multiple hospitals on physician profiles.

Although physicians are all too familiar with the psychologic impact of having multiple responsibilities, the associated impact on practice styles has not been examined systematically. To provide some data on the effects of "work dispersion," we examined the hypothesis that the inpatient resource use of physicians would rise with the number of hospitals in which they work. Data for 1991 from Medicare's National Claims History File were used to profile a sample of attending physicians (n = 33,756) in seven states. The attending physician "profile" was the case mix-adjusted relative value of all physician services (regardless of who delivered them) that were delivered during each patient's hospital stay. Relative value was measured in relative value units, used by Medicare in determining physician payments. The authors then categorized physicians in terms of the number of hospitals to which they admitted patients. Physician profiles were adjusted further to control for geography, physician specialty, and characteristics of the physician's primary (ie, most used) hospital. One third of the physicians in the sample had admissions to more than one hospital. Physicians working in one hospital had inpatient practice profiles 2.1% below the sample mean. Additional hospital affiliations were associated with progressively higher profiles: two hospitals, 2.3% above the mean; three hospitals, 4.5% above; four hospitals, 8.2% above; and five or more hospitals, 11.5% above (all P < 0.01). The practice of medicine in more than one hospital is associated with higher inpatient profiles and shows a dose-response relationship. Physicians and policy makers will need to consider carefully whether there are any associated benefits to justify the increased cost.

Adult↗

A taxonomy of adolescent health: development of the adolescent health profile-types.

OBJECTIVES: The aim of this study was to develop a taxonomy of health profile-types that describe adolescents' patterns of health as self-reported on a health status questionnaire. The intent was to be able to assign individuals to mutually exclusive and exhaustive groups that characterize the important aspects of their health and need for health services. METHODS: Cluster analytic empirical methods and clinically based conceptual methods were used to identify patterns of health in samples of adolescents from schools and from clinics that serve adolescents with chronic conditions and acute illnesses. Individuals with similar patterns of scores across multiple domains were assigned to the same profile-type. Results from the empirical and conceptually based methods were integrated to produce a practical system for assigning youths to profile-types. RESULTS: Four domains of health (Satisfaction, Discomfort, Risks and Resilience) were used to group individuals into 13 distinct profile-types. The profile-types were characterized primarily by the number of domains in which health is poor, identifying the unique combinations of problems that characterize different subgroups of adolescents. CONCLUSIONS: This method of reporting the information available on health status surveys is potentially a more informative way of identifying and classifying the health needs of subgroups in the population than is available from global scores or multiple scale scores. The reliability and validity of this taxonomy of health profile-types for the purposes of planning and evaluating health services must be demonstrated. That is the purpose of the accompanying study.

Acute Disease↗

Improved sensitivity in bone scintigraphy using quantitative spinal profile analysis.

Full-length skeletal scintiscans were acquired onto a data processor in a series of 256 X 256 matrices. A series of interactive computer programs enables the operator to select profiles down the spine and to standardize them by interpolation to a standard length and by normalization to a given count level. The counts within any section of a profile can then be calculated and the profile examined for any significant deviation from a reference 'normal' curve. In a study of 68 patients, 66% of the spinal profiles were judged abnormal, compared with 26% of scans assessed by visual inspection alone. Of 14 patients with positive profiles and negative or equivocal visually assessed scans, 11 had developed metastases within 14 months of the scan. All five patients with positive profile and raised alkaline phosphatase have died of metastatic disease. The technique appears to increase the sensitivity of bone scintigraphy.

Bone Neoplasms↗

Radiographic spinal profile changes induced by cage design after posterior lumbar interbody fusion preliminary report of a study with wedged implants.

STUDY DESIGN: A prospective comparative radiographic study between two geometrically varying implants utilized in single-level posterior lumbar interbody fusion (PLIF) was performed. OBJECTIVE: The aim of this study was to determine the influence of 4 degrees wedged cages on postoperative lateral lumbar spinal profile. SUMMARY OF BACKGROUND DATA: The biomechanical and clinical importance of realigning the sagittal lumbar profile in surgical management of spinal instabilities is known. Wedged cages are therefore increasingly attaining popularity in PLIF. As yet the significance of wedged implants on postoperative sagittal spinal profile has not been assessed. METHODS: Forty patients were randomly assigned to two equal-sized groups. In one group rectangular cages and in the second group cages with a wedged design and an inclination of 4 degrees were implanted. Quantitative assessment of the lumbar spinal profile on standing neutral lateral radiographs was performed before surgery as well as 6 weeks and 12 months after surgery. Results were statistically compared. RESULTS: A significant improvement of lumbar sagittal profile after use of 4 degrees wedged compared with nonwedged cages was not found. The greatest effect on lumbar profile and segmental lordosis was observed in fusion of segment L4-L5 with 4 degrees wedged cages. CONCLUSIONS: These results show that normal sagittal alignment after single-level lumbar fusion can be achieved with rectangular and 4 degrees wedged cages. Although results after utilization of 4 degrees wedged cages do not significantly differ, these implants offer the surgeon one more sizing variation with which physiologic lumbar lordosis may be attained. The biomechanical implications of wedged implants on the rigidity of a fused segment remain to be analyzed.

Female↗

Cyclosporin A absorption profiles in pediatric renal transplant recipients predict the risk of acute rejection.

The current focus of cyclosporin A (CsA) monitoring in adult transplantation for optimized immunosuppression is on the early portion of the CsA area under the concentration-time curve (AUC), particularly in the first 4 hours postdose, designated as AUC(0-4), and on the blood concentration 2 hours postdose (C2) as a highly predictive marker for AUC(0-4). Because data in pediatric patients are scarce, full-time (12 hours) and absorption profiles of CsA were analyzed in relation to CsA effectiveness in 61 pediatric renal transplant recipients aged 3.2 to 17.4 years on an immunosuppressive triple regimen with CsA, mycophenolate mofetil, and methylprednisolone. CsA dosing was based on body surface area and adjusted to CsA trough levels. Pharmacokinetic (PK) profiles were obtained 1 and 3 weeks (initial period) and 3 and 6 months posttransplant (stable period). Patients with an AUC(0-4) < 4400 microg x h/L at both PK sampling periods in the first 3 weeks posttransplant had an adjusted relative risk of 48.4% to suffer an acute rejection episode (ARE), whereas in patients with at least 1 AUC0-4 above this threshold, the adjusted relative risk for an ARE was only 13.1% (P < 0.02). The single PK parameters C0 or C2 did not discriminate between patients with and without acute rejection. The PK parameters C1.25 (r2 = 0.64) or C2 (r2 = 0.60) showed a stronger relationship to the absorption profile (AUC(0-4)) than C0 (r2 = 0.15). An abbreviated profile consisting of the PK variables C(0.5;2) or C(0;0.5;2) showed the closest correlation to the absorption profile (r2 = 0.89) and the lowest percentage prediction error. These data indicate that absorption profiling in pediatric renal transplant recipients has the potential to optimize immunosuppressive therapy with CsA.

Administration, Oral↗

An epidemiologic assessment of genomic profiling for measuring susceptibility to common diseases and targeting interventions.

PURPOSE: The current clinical value of genomic profiling (testing for genotypes at multiple loci) for assessing susceptibility to common diseases and targeting behavioral and medical interventions is questionable. As common diseases result from many gene-environment interactions, epidemiologic studies should be used to examine the value of genomic profiling in terms of clinical validity (future disease positive and negative predictive value stratified by exposure), clinical utility (targeted interventions to reduce disease risk among persons with the profile) and public health utility (comparing reduction of disease burden in the population based on genomic profiling to population-wide interventions). METHODS: We investigate these parameters for a hypothetical common disease (5% lifetime risk), for which 3 genetic variants at different loci and one environmental exposure are risk factors. RESULTS: We show that even for modest effects of each variant alone (risk ratios from 1.5-3.0) and modest interactions between the exposure and the genes, the disease predictive value for people with 2 or more variants (especially 3) can be quite high (50-100%) in the presence of a modifiable exposure. Individual risks can then be reduced by targeted exposure intervention among persons with the genotype. However, the predictive value for multiple genotypes is much lower for rarer diseases (< 1 per 1000). Also, with increasing number of genes in a profile, the population impact of disease reduction for targeted intervention based on genotype will be smaller, especially for rare genotypes, weak associations, and weak interactions. CONCLUSION: To assess the value of genomic profiling, well-designed epidemiologic studies are needed to quantify disease risks, in addition to costs, benefits, and risks for testing and interventions.

DNA Fingerprinting↗

Sputter-depth profiling for thin-film analysis.

Following a brief historical background, the concepts and the present state of sputter-depth profiling for thin-film analysis are outlined. There are two main branches: either the removed matter (as in mass- or optical-spectroscopy-based secondary-ion mass spectrometry or glow-discharge optical emission spectroscopy), or the remaining surface (as in Auger electron spectroscopy and X-ray photoelectron spectroscopy) is characterized. These complementary methods show the same result if there is no preferential sputtering of a component. The common root of both is the fundamental ion-solid interaction. Understanding of how the latter influences the depth resolution has led to important improvements in experimental profiling conditions such as sample rotation and the use of low-energy ions at glancing incidence. Modern surface-analysis instruments can provide high-resolution depth profiles on the nanometre scale. Mathematical models of different sophistication were developed to allow deconvolution of the measured profile or quantification by reconstruction of the in-depth distribution of composition. For the latter purpose, the usefulness of the so-called mixing-roughness-information (MRI) depth model is outlined on several thin-film structures (e.g. AlAs/GaAs and Si/Ge), including its extension to quantification of sputter-depth profiles in layer structures with preferential sputtering of one component (Ta/Si). Using the MRI model, diffusion coefficients at interfaces as low as 10(-22) m(2) s(-1) can be determined. Fundamental limitations of sputter-depth profiling are mainly traced back to the stochastic nature of primary-particle energy transfer to the sputtered particle, promoting atomic mixing and the development of surface roughness. Owing to more sophisticated experimental methods, such as low-energy cluster ion bombardment, glancing ion incidence or 'backside' sputtering, these ultimate limitations can be reduced to the atomic monolayer scale.

Journal Article↗

Identification of novel species-specific antigens of Mycoplasma hyopneumoniae by preparative SDS-PAGE ELISA profiling.

Mycoplasma hyopneumoniae, M. hyorhinis and M. flocculare are commonly isolated from the respiratory tract of pigs and are phylogenetically related. The identification and characterization of antigens specific for M. hyopneumoniae is crucial for the development of serological reagents and for understanding the mechanisms of pathogenicity of this pathogen. Protein and antigen profiles of six strains of M. hyopneumoniae, four strains of M. hyorhinis and a type strain of M. flocculare were compared using SDS-PAGE and immunoblotting. Five strains of M. hyopneumoniae originally isolated from diverse geographical regions produced similar protein and antigen profiles. One strain, C1735/2, produced a unique protein profile and was poorly immunoreactive, suggesting that some strains of M. hyopneumoniae may possess a structurally modified repertoire of antigens. Major M. hyopneumoniae antigens with molecular masses of approximately 36, 43, 48, 52, 76, 78, 80, 82, 94, 106, 114 and 200 kDa were identified by immunoblotting using hyperimmune pig sera raised against both high and low passage strains of M. hyopneumoniae. Porcine hyperimmune sera raised against the GDL type strain of M. hyorhinis reacted strongly with all M. hyorhinis strains although the profiles displayed considerable variation. Major antigens of molecular mass 42, 49, 52, 78, 80 and 82 kDa were identified in type strains GDL and BTS-7 and field strain 2; however, field strain 1 produced a unique profile. A preparative SDS-PAGE profiling (PPP) technique was developed which enabled quantification of the immunoreactivity of denatured antigens with porcine serum by ELISA. PPP facilitated the rapid identification of species-specific and cross-reactive antigens among the three mycoplasma species. PPP studies revealed several strongly immunoreactive M. hyopneumoniae-specific antigens of 43, 76, 94, 114 and 200 kDa as well as antigens of molecular mass between 52 and 62 kDa which were not apparent in immunoblotting studies. Rabbit monospecific anti-42 kDa serum reacted specifically with a 43 kDa antigen in whole cell lysates of geographically diverse strains of M. hyopneumoniae and failed to cross-react with M. flocculare or M. hyorhinis whole cell lysates. This study has identified a number of M. hyopneumoniae-specific antigens which warrant further investigation to determine their potential as diagnostic reagents and the role they play, if any, in pathogenicity.

Animals↗

Reconstruction of sculpture from its profiles with unknown camera positions.

Profiles of a sculpture provide rich information about its geometry, and can be used for shape recovery under known camera motion. By exploiting correspondences induced by epipolar tangents on the profiles, a successful solution to motion estimation from profiles has been developed in the special case of circular motion. The main drawbacks of using circular motion alone, namely the difficulty in adding new views and part of the object always being invisible, can be overcome by incorporating arbitrary general views of the object and registering its new profiles with the set of profiles resulted from the circular motion. In this paper, we describe a complete and practical system for producing a three-dimensional (3-D) model from uncalibrated images of an arbitrary object using its profiles alone. Experimental results on various objects are presented, demonstrating the quality of the reconstructions using the estimated motion.

Algorithms↗

The IclR family of transcriptional activators and repressors can be defined by a single profile.

In the last decade enormous advances in life sciences have been possible due to the information obtained from DNA sequencing projects. The optimal interpretation and analysis of genome sequence data requires the precise annotation and classification of proteins deduced from open reading frames, which is usually done with the help of family-specific signatures. Here we report a novel profile for the IclR type of transcriptional activators and repressors. In contrast to profiles for other families of transcriptional regulators, the new IclR profile is located outside the helix-turn-helix DNA-binding motif. We provide evidence that the new profile is more specific than any of the existing signatures for this family of regulators. More than 500 representatives of this family were identified with this profile. A database on bacterial regulators (http://www.bactregulators.org) was built to compile and regroup the sequences with the aid of the new profile.

Amino Acid Sequence↗

Profiles of social competence among low-income African American preschool children.

Relations between children's personal attributes and peer play competence were investigated in a sample of 141 African American preschool children who participated in Head Start. Variable-oriented analyses confirmed that dispositions of temperament, emotion regulation, autonomy, and language were related to children's peer play competence in the classroom. Person-oriented analyses revealed distinctive profiles of personal attributes linked to adaptive preschool social functioning. A small group of resilient children whose profile was characterized by highly adaptable temperament, ability to approach new situations, and above average vocabulary development evidenced the greatest social competence with peers. Children who were disruptive with peers were equally divided between two profiles characterized by inattention and activity, but with differential performance on vocabulary tasks. A profile containing calm, reticent children was the group least likely to engage in disruptive peer play. Inspection of the six profiles revealed the within-group variability for this economically disadvantaged sample and illustrated the differential importance of temperament, regulation, and language constructs. Findings from the profile analyses and relations with peer competence inform the study of resilience in social development for urban African American children who participate in early intervention preschool programs.

Black or African American↗