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At least 991 records · Page 55Linked to original sources
PubMed1999

Electrospray ionization mass spectrometry: analysis of the Ca2+-binding properties of human recombinant alpha-parvalbumin and nine mutant proteins.

A set of 10 different recombinant human parvalbumins was used to establish a method for the investigation of the Ca2+-binding properties of proteins by electrospray ionization mass spectrometry (ESI-MS). Human PVWT was found to bind 2 mol Ca2+ ions/mol of protein, whereas its mutants (PVE101V, PVD90A, PVE62V, PVD51A, PVD90A,E101V, PVE62V,E101V, PVD51A,D90A, PVD51A,E62V, PVD51A,E62V, D90A,E101V) containing inactivating substitutions in the Ca2+-binding loops bind 0 or 1 Ca2+ ion per protein molecule, depending on the degree of inactivation. These findings fully agree with previously reported results obtained by flow dialysis experiments. The RP-HPLC desalted metal-free proteins were analyzed in 10 mM ammonium acetate at pH 7.0. The experimental conditions were optimized with the recombinant parvalbumin test system before analyzing the Ca2+-binding properties of rat and murine parvalbumins in muscle tissue extracts. ESI-MS revealed that (i) rat and murine alpha-parvalbumins each bind specifically two Ca2+ ions per protein molecule and (ii) both extracted parvalbumins were found to be posttranslationally modified; each protein is acetylated at the N-terminus. Finally, during our investigations of the murine parvalbumin a sequencing error was detected at the C-terminus where the amino acid at position 109 is Ser and not Thr as mentioned in the SwissProt data base (Accession No. P32848). This work demonstrates the great potential of the ESI-MS technique as a sensitive, specific, and rapid method for direct identification and determination of the stoichiometry of Ca2+-binding proteins and other metalloproteins.

Animals↗
PubMed2003

Need for recovery from work related fatigue and its role in the development and prediction of subjective health complaints.

AIMS: To present the available empirical evidence for the assumed position of the concept of work related fatigue as: (1) short term effect of the working day; and (2) an intermediate variable between work demands and the development of subjective health complaints and sickness absence. METHODS: Results from six single occupation studies, conducted between 1996 and 2002, are presented. Work demands (working hours, decision latitude, break control/autonomy, and mental, emotional, and physical demands) were assessed through validated scales. Work related fatigue was represented and assessed by means of the need for recovery after working time scale in all studies. Subjective health complaints and duration of sickness absence were quantified with the same instruments in most studies as well. Both cross sectional studies (four) as well as prospective studies (two; up to two years follow up) were performed. Cross sectional data of 3820 workers, in total, were available. Prospective data were accessible for 1200 workers in industry and health care. Models were tested with stepwise multiple regression analyses. RESULTS: Strong associations between work demands and need for recovery were found in different occupations. The variance explained in need for recovery by work demands, age, and (baseline) need for recovery ranged between 14% and 48% in both types of studies. The amount of explained variance by work demands, age, and (baseline) need for recovery in subjective health complaints ranged between 24% and 58% in the different occupations. The prospective data showed the prognostic value of need for recovery in relation to subjective health complaints (in terms of psychosomatic complaints, emotional exhaustion, or sleep problems) and duration of future sickness absence. CONCLUSIONS: The hypothesised role for work related fatigue as a link in the causal string of events, that is assumed to exist between repeated adverse work demands and the development of work related stress reactions, (psychological) overload and, eventually, health problems, was confirmed.

Adult↗
PubMed2006

Analysis of the HUPO Brain Proteome reference samples using 2-D DIGE and 2-D LC-MS/MS.

Within the Human Proteome Organization (HUPO) Brain Proteome Project, a pilot study was launched with reference samples shipped to nine international laboratories (see Hamacher et al., this Special Issue) to evaluate different proteome approaches in neuroscience and to build up a first version of a brain protein database. One part of the study addresses quantitative proteome alterations between three developmental stages (embryonic day 16; postnatal day 7; 8 weeks) of mouse brains. Five brains per stage were differentially analyzed by 2-D DIGE using internal standardization and overlapping pH gradients (pH 4-7 and 6-9). In total, 214 protein spots showing stage-dependent intensity alterations (> two-fold) were detected, 56 of which were identified. Several of them, e.g. members of the dihydropyrimidinase family, are known to be associated with brain development. To feed the HUPO BPP brain protein database, a robust 2-D LC-MS/MS method was applied to murine postnatal day 7 and human post-mortem brain samples. Using MASCOT and the IPI database, 350 human and 481 mouse proteins could be identified by at least two different peptides. The data are accessible through the PRIDE database (http://www.ebi.ac.uk/pride/).

Aging↗
PubMed2005

Identification of estrogen-responsive genes using a genome-wide analysis of promoter elements for transcription factor binding sites.

We developed a pipeline to identify novel genes regulated by the steroid hormone-dependent transcription factor, estrogen receptor, through a systematic analysis of upstream regions of all human and mouse genes. We built a data base of putative promoter regions for 23,077 human and 19,984 mouse transcripts from National Center for Biotechnology Information annotation and 8793 human and 6785 mouse promoters from the Data Base of Transcriptional Start Sites. We used this data base of putative promoters to identify potential targets of estrogen receptor by identifying estrogen response elements (EREs) in their promoters. Our program correctly identified EREs in genes known to be regulated by estrogen in addition to several new genes whose putative promoters contained EREs. We validated six genes (KIAA1243, NRIP1, MADH9, NME3, TPD52L, and ABCG2) to be estrogen-responsive in MCF7 cells using reverse transcription PCR. To allow for extensibility of our program in identifying targets of other transcription factors, we have built a Web interface to access our data base and programs. Our Web-based program for Promoter Analysis of Genome, PAGen@UIC, allows a user to identify putative target genes for vertebrate transcription factors through the analysis of their upstream sequences. The interface allows the user to search the human and mouse promoter data bases for potential target genes containing one or more listed transcription factor binding sites (TFBSs) in their upstream elements, using either regular expression-based consensus or position weight matrices. The data base can also be searched for promoters harboring user-defined TFBSs given as a consensus or a position weight matrix. Furthermore, the user can retrieve putative promoter sequences for any given gene together with identified TFBSs located on its promoter. Orthologous promoters are also analyzed to determine conserved elements.

Algorithms↗
PubMed2005

Human-computer interaction reflected in the design of user interfaces for general practitioners.

PURPOSE: To address the problem of properly built health information systems in general practice as an important issue for their approval and use in clinical practice. We present how a national general practitioner (GP) network was built, put in practice and several results of its activity seen from the clinician's and the software application team's points of view. METHODS: We used a multi-level incremental development appropriate for the conditions of the required information system. After the development of the first version of the software components (based on rapid prototyping) of the sentinel network, a questionnaire addressed the needs and improvements required by the health professionals. Based on the answers, the functionality of the system and the interface were improved regarding the real needs expressed by the end-users. RESULTS: The network is functional and the collected data from the network are being processed using statistical methods. The academic software team developed a GP application that is well received by the GPs in the network, as resulted from the survey and discussions during the training period. As an added confirmation, several GPs outside the network enrolled after seeing the software at work. Another confirmation that we did a good job was that after the final presentation of the results of the project a representative from the Romanian Society for Cardiology expressed the wish of this society to access the data yielded by the network.

Computer Communication Networks↗
PubMed2001

Functional classification of interferon-stimulated genes identified using microarrays.

Interferons (IFNs) are a family of multifunctional cytokines that activate transcription of subsets of genes. The gene products induced by IFNs are responsible for IFN antiviral, antiproliferative, and immunomodulatory properties. To obtain a more comprehensive list and a better understanding of the genes regulated by IFNs, we compiled data from many experiments, using two different microarray formats. The combined data sets identified >300 IFN-stimulated genes (ISGs). To provide new insight into IFN-induced cellular phenotypes, we assigned these ISGs to functional categories. The data are accessible on the World Wide Web at http://www.lerner.ccf.org/labs/williams/, including functional categories and individual genes listed in a searchable database. The entries are linked to GenBank and Unigene sequence information and other resources. The goal is to eventually compile a comprehensive list of all ISGs. Recognition of the functions of the ISGs and their specific roles in the biological effects of IFNs is leading to a greater appreciation of the many facets of these intriguing and essential cytokines. This review focuses on the functions of the ISGs identified by analyzing the microarray data and focuses particularly on new insights into the protein kinase RNA-regulated (PRKR) protein, which have been made possible with the availability of PRKR-null mice.

Animals↗
PubMed2026

Identification Matters: How Data Sharing Affects Pupil Honesty and Engagement in Universal School Well-Being Assessments.

PURPOSE: Universal well-being assessments in schools may support early identification of pupils needing mental health support. However, little is known about how privacy and confidentiality concerns influence pupils' acceptability of assessments and willingness to engage authentically. This study examined how hypothetical identification, where responses are linked to pupils and shared with key stakeholders, affects pupils' anticipated honesty and engagement, and whether known help-seeking barriers predict negative responses. METHODS: Cross-sectional data were collected from 12,377 primary (ages 8-10) and secondary pupils (ages 11-17) across 55 schools in England. Pupils reported whether their responses would change if identifiable and shared with school staff, parents/guardians, or external professionals. Responses indicating reduced honesty or likelihood of disengagement were coded as negative. Predictors were examined using mixed-effects logistic regression models, including demographics, school connectedness, and mental well-being. RESULTS: Identification and data sharing influenced pupils' anticipated engagement, particularly in secondary schools. Identification by school staff elicited the highest proportion of negative responses in both phases, whereas external professionals elicited the fewest. Most primary pupils reported they would respond authentically, while a larger proportion of secondary pupils indicated they would respond less honestly or disengage when responses were identifiable and shared. Across primary and secondary samples, low well-being, low school connectedness, and being female were associated with greater likelihood of negative response. DISCUSSION: Pupils' anticipated engagement with well-being assessments is shaped by who accesses their data, with marked developmental differences. Strengthening trust, privacy, and connectedness, and supporting pupils' autonomy, may improve the acceptability and response accuracy.

Humans↗
PubMed1993

Development of a portable information system: connecting palmtop computers with medical records systems and clinical reference resources.

The portability of palmtop computers makes them an ideal platform to maintain communication between busy physicians and medical information systems. In our academic FHC (Family Health Center) we have developed software that runs on a palmtop computer allowing access to information in the HIS (Hospital Information System) and our FHC's AAMRS (Automated Ambulatory Medical Record System). The resident physicians who staff the hospital and the FHC are frequently at home or otherwise off-site where terminal access is not available. Using a Hewlett-Packard 95LX palmtop computer as the base platform, custom software has been developed to access summary data on in-patients and out-patients. Data is downloaded into a database on a palmtop computer memory card. ASCII data from Medical Information Systems (MIS), is transformed into a database format readable on the palmtop. Our hospital MIS department transmits information daily on our in-patient service (20-30 patients). We also download, weekly, a patient summary on all of our active out-patients in our MUMPS-based AAMRS (2500-3000 patients). Each morning the resident in the Family Practice program updates his palmtop memory card at a central workstation. Palmtop computers with downloaded databases, can be valuable in care of patients when the physical or on-line chart is not easily accessible. They are particularly useful in multi-physician groups when the on-call physician provides care for the patients of other physicians. We have made the palmtop computer even more valuable to physicians by providing an integrated software package.(ABSTRACT TRUNCATED AT 250 WORDS)

Academic Medical Centers↗
PubMed2004

Poverty, out-of-pocket payments and access to health care: evidence from Tajikistan.

Most countries of the Former Soviet Union (FSU) have either initiated or are contemplating reform of the health sector. With negative real income growth and falling government revenues, a key concern of many governments is to secure additional finance through non-budgetary sources such as hypothecated payroll taxes, voluntary insurance, and increased private finance through patient cost-sharing. However, before such reforms can be considered, information is needed both on the current levels and distribution of household expenditures on health care, and the extent to which increased charges may affect access to health services, especially amongst the poor. This paper uses the Tajikistan Livings Standard Survey to investigate the level and distribution of out-of-pocket payments for health care in Tajikistan and to examine the extent to which such payments act as barriers to health-care access. The data show that there are significant differences in health-care utilisation rates across socio-economic groups and that these differences are related to ability to pay. Official and informal payments are acting both to deter people from seeking medical assistance and once advice has been sought, from receiving the most appropriate treatment. Despite informal exemptions, out-of-pocket payments for health care are exacting a high toll on household welfare with households being forced to sell assets or go into debt to meet the costs of care. Urgent action is needed to ensure equity in access to health care.

Adolescent↗
PubMed1998

A patient-centric approach to telemedicine database development.

Computer and telecommunications technologies have unleashed a wide range of powerful tools for gathering, storing, and distributing patient information. Computerized records enable healthcare providers to rapidly access patient data and to closely monitor patients from a distance. These significant advantages can be further extended by using the technology to more fully involve patients in their own healthcare management. A patient-centric approach to telemedicine means that the patient takes on additional responsibility and control, and the benefits from increased patient involvement will translate into improved compliance, reduced litigation, lower costs, and better outcomes. Furthermore, there are often important ethical questions that are best decided by the informed patient. Patients have a right to know what information is being gathered and who will be authorized to access that information. Current health information systems do not adequately address these issues, and telemedicine applications--particularly home based telemedicine--is forcing everyone to take a closer look at patients' roles in their own healthcare. In this presentation, a patient-centric home telemedicine database is described, the limitations are discussed, and future directions are proposed.

Computer Communication Networks↗
PubMed2005

Uncovering regulatory pathways that affect hematopoietic stem cell function using 'genetical genomics'.

We combined large-scale mRNA expression analysis and gene mapping to identify genes and loci that control hematopoietic stem cell (HSC) function. We measured mRNA expression levels in purified HSCs isolated from a panel of densely genotyped recombinant inbred mouse strains. We mapped quantitative trait loci (QTLs) associated with variation in expression of thousands of transcripts. By comparing the physical transcript position with the location of the controlling QTL, we identified polymorphic cis-acting stem cell genes. We also identified multiple trans-acting control loci that modify expression of large numbers of genes. These groups of coregulated transcripts identify pathways that specify variation in stem cells. We illustrate this concept with the identification of candidate genes involved with HSC turnover. We compared expression QTLs in HSCs and brain from the same mice and identified both shared and tissue-specific QTLs. Our data are accessible through WebQTL, a web-based interface that allows custom genetic linkage analysis and identification of coregulated transcripts.

Carrier Proteins↗
PubMed1991

Nucleotide sequence of cDNA covering the N-terminus of human tripeptidyl peptidase II.

A cDNA clone, with an insert of 3068 bp, encoding the N-terminus of human tripeptidyl peptidase II (TPP II) has been isolated and sequenced. Together with previous data (GenBank accession no J05299) a total of 4634 bp of the nucleotide sequence for TPP II can now be assembled. There is an in-frame methionine at position 8, which probably represents the starting point of translation, indicating that the complete coding sequence for TPP II now has been determined.

Amino Acid Sequence↗
PubMed2006

UCSF tomography: an integrated software suite for real-time electron microscopic tomographic data collection, alignment, and reconstruction.

A real-time alignment and reconstruction scheme for electron microscopic tomography (EMT) has been developed and integrated within our UCSF tomography data collection software. This newly integrated software suite provides full automation from data collection to real-time reconstruction by which the three-dimensional (3D) reconstructed volume is immediately made available at the end of each data collection. Real-time reconstruction is achieved by calculating a weighted back-projection on a small Linux cluster (five dual-processor compute nodes) concurrently with the UCSF tomography data collection running on the microscope's computer, and using the fiducial-marker free alignment data generated during the data collection process. The real-time reconstructed 3D volume provides users with immediate feedback to fully asses all aspects of the experiment ranging from sample choice, ice thickness, experimental parameters to the quality of specimen preparation. This information can be used to guide subsequent data collections. Access to the reconstruction is especially useful in low-dose cryo EMT where such information is very difficult to obtain due to extraordinary low signal to noise ratio in each 2D image. In our environment, we generally collect 2048 x 2048 pixel images which are subsequently computationally binned four-fold for the on-line reconstruction. Based upon experiments performed with thick and cryo specimens at various CCD magnifications (50000x-80000x), alignment accuracy is sufficient to support this reduced resolution but should be refined before calculating a full resolution reconstruction. The reduced resolution has proven to be quite adequate to assess sample quality, or to screen for the best data set for full-resolution reconstruction, significantly improving both productivity and efficiency of system resources. The total time from start of data collection to a final reconstructed volume (512 x 512 x 256 pixels) is about 50 min for a +/-70 degrees 2k x 2k pixel tilt series acquired at every 1 degrees.

Algorithms↗
PubMed2004

[The interest of cholesterol levels in young children. Study in a population of 4,697 children aged 4].

INTRODUCTION: There is a need to dispose of normal cholesterol levels in young children. In view of the paucity of such data in France, we analysed the results of screening conducted in children. METHOD: We analysed the cholesterol levels of 4697 children, with a mean age of 4.3 years, attending a medical check-up in a Child Health Unit in a National Health Scheme centre in Paris. All the children were recruited consecutively during the year 2002. RESULTS: The mean cholesterol level was of 4.4 mmol/L +/- 0.75. We detected a slight gender-related variation (the mean in girls and boys were of 4.5 +/- 0.76 and 4.4 +/- 0.74 respectively). The 95 percentile in girls and boys were 5.7 and 5.6 mmol/L, respectively. DISCUSSION: For the first time in France, we now have access to data on normal cholesterol levels in a large cohort of 4 year-old children. Screening for hypercholesterolaemia in children provides the opportunity to discuss dietary counselling.

Child, Preschool↗
PubMed1994

Information, market government, and health policy: a study of health data organizations in the states.

Information is essential to the success of market-oriented policies. Information on health care costs and quality is collected and distributed by state governments through health data organizations (HDOs) to enhance competition and lower costs in the medical industry and to improve consumer choice among medical alternatives. This article examines the information collected, produced, and distributed by state health data organizations in Colorado and Pennsylvania. Findings reveal that information was not the objective determinant of choice and competition as market-oriented policy designers had hoped. Nor did market-oriented bureaucracies produce and distribute data readily accessible for public choice. Instead, information produced and distributed by these HDOs was the result of political and bureaucratic exercises that conform much more to classic interest group policymaking and captured bureaucracies than to contemporary market-oriented government ideals. The findings underscore the extraordinary difficulties facing federal-level policy designers as they contemplate introducing market-oriented health care policies on the national level.

Colorado↗
PubMed2004

Techniques for optimization of queries on integrated biological resources.

Today, scientific data are inevitably digitized, stored in a wide variety of formats, and are accessible over the Internet. Scientific discovery increasingly involves accessing multiple heterogeneous data sources, integrating the results of complex queries, and applying further analysis and visualization applications in order to collect datasets of interest. Building a scientific integration platform to support these critical tasks requires accessing and manipulating data extracted from flat files or databases, documents retrieved from the Web, as well as data that are locally materialized in warehouses or generated by software. The lack of efficiency of existing approaches can significantly affect the process with lengthy delays while accessing critical resources or with the failure of the system to report any results. Some queries take so much time to be answered that their results are returned via email, making their integration with other results a tedious task. This paper presents several issues that need to be addressed to provide seamless and efficient integration of biomolecular data. Identified challenges include: capturing and representing various domain specific computational capabilities supported by a source including sequence or text search engines and traditional query processing; developing a methodology to acquire and represent semantic knowledge and metadata about source contents, overlap in source contents, and access costs; developing cost and semantics based decision support tools to select sources and capabilities, and to generate efficient query evaluation plans.

Algorithms↗
PubMed2001

Non-amplification of an allele of the D8S1179 locus due to a point mutation.

During a population study of 128 Korean families (626 persons) with the AmpF/STR Profiler Plus PCR amplification system, we found an unusual homozygous genotype at the D8S1179 locus in 4 families. Therefore, a new pair of primers was designed for the D8S1179 locus from GenBank data (GenBank Accession No. G08710) to evaluate the cause. The newly designed primers amplified alleles that were not amplified with the AmpFlSTR Profiler Plus PCR amplification system. We sequenced alleles of the family members who had non-amplified alleles and we found a G-to-A transition at the position of the 147th base of the GenBank sequence.

Alleles↗
PubMed2006

[Clinical study of the French cohort of Gaucher disease patients].

A census is currently being carried out of the French cohort of Gaucher disease patients. This article describes its preliminary results, obtained by analysing the records of 101 patients for whom clinical and laboratory data were accessible while they were receiving enzyme therapy. At the time of diagnosis, all patients presented with splenomegaly, 70% had asthenia and one in three was already affected by major bone damage. After 1 year of enzyme therapy, splenomegaly had diminished by half and the different scores (asthenia, bone pain and abdominal pain, etc.) had markedly improved, as had the biochemical markers. As for the 6 patients affected by type 3 Gaucher disease and treated with enzyme therapy after the onset of neurological signs, a stabilisation or even some improvement of the disease was observed. In-depth study of the French cohort should make it possible to formulate consensus recommendations for the future, based on well-established data.

1-Deoxynojirimycin↗