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Biomedical subjects

M R Barnes

Publications and source records attributed to M R Barnes.

At least 19 recordsLinked to original sources
PubMed2005

Specific loss of connexin 26 expression in ductal sweat gland epithelium associated with the deletion mutation del(GJB6-D13S1830).

A whole array of cutaneous syndromes is associated with distinct dominant mutations in GJB2 encoding the gap junction protein connexin 26 (C x 26), including Vohwinkel's syndrome and keratitis-ichthyosis-deafness syndrome. In contrast, recessive GJB2 mutations occur in a large proportion of individuals with hearing loss but no obvious dermatological phenotype. Recently, a large deletion of approximately 342 kb, encompassing the coding region of GJB6 encoding C x 30, but not affecting GJB2, was shown to be associated with hearing loss. From analysis of patient skin, we provide immunohistochemical and bioinformatic data to show that the expression of C x 26 is affected by del(GJB6-D13S1830) in a cell-type-specific manner within the sweat gland. This putative regulatory element of C x 26 expression may be a key factor related to the severe or profound deafness associated with del(GJB6-D13S1830).

Chromosome Deletion↗
PubMed2002

Linkage disequilibrium mapping identifies a 390 kb region associated with CYP2D6 poor drug metabolising activity.

The cytochrome p450 enzyme, CYP2D6, metabolises approximately 20% of marketed drugs. CYP2D6 multiple variants are associated with altered enzyme activities. Genotyping 1018 Caucasians for CYP2D6 polymorphisms (G1846A, delT1707, delA2549 and A2935C), known to result in the recessive CYP2D6 poor drug metaboliser (PM) phenotype, identified 41 individuals with predicted PM phenotype. These 41 individuals were classified as 'cases'. Single nucleotide polymorphisms (SNPs) mapping within an 880 kb region flanking CYP2D6, were identified to evaluate potential association between genetic variation and the CYP2D6 PM phenotype. The 41 PM cases and 977 controls were genotyped and analysed for 27 SNPs. Associations were observed across a 390 kb region between 14 SNPs and the PM phenotype (P values from 6.20 x 10(-4) to 4.54 x 10(-35)). Haplotype analysis revealed more significant levels of association (P = 3.54 x 10(-56)). Strong (D' > 0.7) linkage disequilibrium (LD) between SNPs was observed across the same 390 kb region associated with the CYP2D6 phenotype. The observed phenotype:genotype association reached genome-wide levels of significance, and supports the strategy for potential application of LD mapping and whole genome association scans to pharmacogenetic studies.

Chromosome Mapping↗
PubMed2001

Failure to confirm NOTCH4 association with schizophrenia in a large population-based sample from Scotland.

The NOTCH4 gene was recently reported to be associated with schizophrenia based on TDT analysis of 80 British trios. The strongest evidence for association derived from two microsatellites. We genotyped both loci in a large sample of unrelated Scottish schizophrenics and controls, but failed to replicate the reported association, finding instead that each putative schizophrenia-associated allele had a somewhat lower frequency in schizophrenics than in controls.

Alleles↗
PubMed2001

Representing and querying conceptual graphs with relational database management systems is possible.

This is an experimental study on the feasibility of maintaining medical concept dictionaries in production grade relational database management systems (RDBMS.) In the past, RDBMS did not support transitive relational structures and had therefore been unsuitable for managing knowledge bases. The revised SQL-99 standard, however, may change this. In this paper we show that modern RDBMS that support recursive queries are capable of querying transitive relationships in a generic data model. We show a simple but efficient indexed representation of transitive closure. We could confirm that even challenging combined transitive relationships can be queried in SQL.

Artificial Intelligence↗
PubMed2000

Wnt-16a, a novel Wnt-16 isoform, which shows differential expression in adult human tissues.

The WNT genes encode a large family of secreted glycoprotein signalling molecules important from the earliest stages of development through to the adult. We have identified a novel isoform of the recently described WNT family member, Wnt16, following analysis of chromosome 7q31 genomic sequence. We find differential organisation of Wnt16 with the generation of two mRNA isoforms, Wnt16a and Wnt16b. These isoforms differ in the composition of their 5'-UTR and first exons and show evidence of differential expression. In normal human tissues, Wnt16a is expressed at significant levels only in the pancreas, whereas Wnt16b is expressed more ubiquitously with highest levels in adult kidney, placenta, brain, heart, and spleen. Wnt16 is one of a growing number of WNT genes showing evidence of distinct isoforms. We present evidence to suggest that these isoforms may be regulated from alternative promoters and discuss the potential functional differentiation afforded by these WNT isoforms. This may reveal subtle new mechanisms of regulation of WNT expression and function.

5' Untranslated Regions↗
PubMed2000

FrzB-2: a human secreted frizzled-related protein with a potential role in chondrocyte apoptosis.

OBJECTIVE: To characterize a novel secreted frizzled-related protein (SFRP) and determine its tissue distribution at the mRNA and protein level. METHODS: The FrzB-2 gene was identified by expressed sequence tag (EST) analysis of human tissue-derived libraries. Tissue distribution of FrzB-2 mRNA was determined by Northern blot analysis and in situ hybridization. FrzB-2 protein reactivity was localized in human OA articular cartilage by immunocytochemistry, using a polyclonal antibody against a peptide sequence unique to FrzB-2. Apoptosis was detected in articular cartilage sections using Tunel staining. RESULTS: ESTs corresponding to FrzB-2 were found in osteoblast, chondrosarcoma, osteosarcoma, osteoclastoma and synovial fibroblast libraries. FrzB-2 mRNA is expressed in a number of tissues and cell types including bone-related cells and tissues such as primary human osteoblasts and osteoclastoma. In situ hybridization studies showed strong FrzB-2 mRNA expression in human chondrocytes in human osteoarthritic (OA) cartilage but negligible levels in normal cartilage chondrocytes. The FrzB-2 cDNA encodes a secreted 40 kDa protein consisting of 346 amino acids. FrzB-2 is 92. 5% identical to the rat orthologue, DDC-4, which has been shown to be associated with physiological apoptosis. FrzB-2 protein was selectively detected in human OA articular cartilage by immunocytochemistry, using a polyclonal antibody. Consistent with its potential role in apoptosis, positive FrzB-2 staining and Tunel positive nuclei staining were detected in chondrocyte clones in sections of human OA cartilage. CONCLUSION: These data suggest that FrzB-2 may play a role in apoptosis and that the expression of this protein may be important in the pathogenesis of human OA.

Amino Acid Sequence↗
PubMed2000

A comparison of 2 modern femoral cementing techniques: analysis by cement-bone interface pressure measurements, computerized image analysis, and static mechanical testing.

Modern cementing techniques aim to improve microinterlock and to reduce aseptic loosening. The Norwegian and Swedish Arthroplasty Registers have shown an increased risk of revision using reduced-viscosity cement. We have compared 2 modern cementing techniques using retrograde insertion of normal-viscosity and reduced-viscosity cements. Laboratory-simulated arthroplasty was performed in paired human femora. Performance was evaluated by measuring pressures generated during cementation, cement penetration, and shear strength of the prosthesis-cement and bone-cement interfaces. Large differences exist between these 2 modern techniques. Despite no statistical differences between the pressure measurements with the 2 techniques, greater penetration of reduced-viscosity cement was found proximally, with a trend toward increased penetration of the more viscous cement distally. Areas of greater cement penetration with reduced-viscosity cement proximally produced higher values of ultimate shear strength. Both techniques showed a progressive increase in the shear strength as the level of the section progressed toward the tip of the prosthesis. There is a trend with both techniques for the distal fixation to be stronger.

Arthroplasty, Replacement, Hip↗
PubMed2000

Cloning and characterisation of ITGAV, the genomic sequence for human cell adhesion protein (vitronectin) receptor alpha subunit, CD51.

The integrin family of receptors serves as major receptors for extracellular matrix-mediated cell adhesion and migration, cytoskeletal organisation, cell proliferation, survival, and differentiation. The alpha-V integrins consist of a subset which share a common alpha-V subunit combined with one of five beta subunits (beta-1, 3, 5, 6, or 8). The alpha-V integrins have been implicated in a number of developmental processes, including vasculogenesis and angiogenesis, and are therapeutic targets for inhibition of angiogenesis and osteoporosis. The human cDNA for alpha-V integrin (ITGAV) consists of a 5,717-bp transcript with a coding sequence (CDS) of 3,146 bp encoding a 150-kDa mature peptide. Here we describe the gene structure of ITGAV.

Antigens, CD↗
PubMed1999

Identification of a novel mutation R42P in the gap junction protein beta-3 associated with autosomal dominant erythrokeratoderma variabilis.

We report a missense mutation in the gap junction protein beta-3 (encoding Connexin 31), which was detected in only the affected members of a family in which the autosomal dominant skin disease erythrokeratoderma variabilis was segregating. The nucleotide change results in an arginine to proline substitution in codon 42. This residue is positioned on the first transmembrane/first extracellular domain of the gap junction protein with the mutation replacing a negatively charged residue with a nonpolar residue. This change may disrupt the conformation of the protein and voltage gating polarity leading to impaired channel function.

Connexins↗
PubMed1999

Effective audit trails--a taxonomy for determination of information requirements.

Current methods of detecting confidentiality breaches in electronic medical record systems are inadequate, partially due to the lack of necessary information at the point of audit trail analysis. In order to determine the information requirements for effective audit trail analysis, we have formulated a taxonomy of confidentiality breaches. By considering scenarios in which an inappropriate access might occur, we have identified "indicators" of confidentiality breaches, which may be thought of as evidence suggesting the possibility that a confidentiality breach has occurred. The collection of facts needed to describe the indicators provides insight into the types of information needed to improve confidentiality breach detection. Much of the information needed is unlikely to be available in the patient record. Research is needed exploring means of collecting and utilizing information from sources other than the patient record for use in improving patient information security.

Computer Security↗
PubMed1999

Using external data sources to improve audit trail analysis.

Audit trail analysis is the primary means of detection of inappropriate use of the medical record. While audit logs contain large amounts of information, the information required to determine useful user-patient relationships is often not present. Adequate information isn't present because most audit trail analysis systems rely on the limited information available within the medical record system. We report a feature of the STAR (System for Text Archive and Retrieval) audit analysis system where information available in the medical record is augmented with external information sources such as: database sources, Light-weight Directory Access Protocol (LDAP) server sources, and World Wide Web (WWW) database sources. We discuss several issues that arise when combining the information from each of these disparate information sources. Furthermore, we explain how the enhanced person specific information obtained can be used to determine user-patient relationships that might signify a motive for inappropriately accessing a patient's medical record.

Computer Security↗
PubMed1998

Large scale database scrubbing using object oriented software components.

Now that case managers, quality improvement teams, and researchers use medical databases extensively, the ability to share and disseminate such databases while maintaining patient confidentiality is paramount. A process called scrubbing addresses this problem by removing personally identifying information while keeping the integrity of the medical information intact. Scrubbing entire databases, containing multiple tables, requires that the implicit relationships between data elements in different tables of the database be maintained. To address this issue we developed DBScrub, a Java program that interfaces with any JDBC compliant database and scrubs the database while maintaining the implicit relationships within it. DBScrub uses a small number of highly configurable object-oriented software components to carry out the scrubbing. We describe the structure of these software components and how they maintain the implicit relationships within the database.

Confidentiality↗
PubMed1997

A 3-(3-hydroxyphenyl)propionic acid catabolic pathway in Rhodococcus globerulus PWD1: cloning and characterization of the hpp operon.

Rhodococcus globerulus PWD1, a soil isolate from a polluted site in The Netherlands, is able to degrade a broad range of aromatic compounds. A novel gene cluster which appears to encode a pathway for the degradation of phenolic acids such as 3-(3-hydroxyphenyl)propionate (3HPP) has been cloned from the chromosome of this organism. Sequence analysis of a 7-kb region identified five open reading frames (ORFs). Analysis of mRNA showed that the genes were expressed during growth on 3HPP and 3-hydroxyphenylacetate (3HPA) but not during growth on m-cresol or succinate. The first ORF, hppA, which appears to be separately transcribed, had considerable amino acid identity with a number of hydroxylases. Transcriptional analysis indicates that the next four ORFs, hppCBKR, which are tightly clustered, constitute a single operon. These genes appear to encode a hydroxymuconic semialdehyde hydrolase (HppC), an extradiol dioxygenase (HppB), a membrane transport protein (HppK), and a member of the IclR family of regulatory proteins (HppR). The activities of HppB and HppC have been confirmed by enzyme assay of Escherichia coli hosts. The substrate specificity of HppB expressed from the cloned gene matches that of the meta-cleavage dioxygenase expressed from wild-type Rhodococcus grown on both 3HPP and 3HPA and is considerably more active against acid than against neutral catechols. The deduced amino acid sequences of the gene products have a recognizable homology with a broad range of enzymes and proteins involved in biodegradation and appear most similar to the mhp operon from E. coli K-12, which also encodes the degradation of 3HPP.

Bacterial Proteins↗
PubMed1997

Cement pressurisation during hip replacement.

The newer techniques of cementing aim to improve interlock between cement and bone around a femoral stem by combining high pressure and reduced viscosity. This may produce increased embolisation of fat and marrow leading to hypotension, impaired pulmonary gas exchange and death. For this reason the use of high pressures has been questioned. We compared finger-packing with the use of a cement gun by measuring intramedullary pressures during the cementing of 31 total hip replacements and measuring physiological changes in 19 patients. We also measured pressure in more detail in a laboratory model. In the clinical series the higher pressures were produced by using a gun, but this caused less physiological disturbance than finger-packing. The laboratory studies showed more consistent results with the gun technique, but for both methods of cementing the highest pressures were generated during the insertion of the stem of the prosthesis.

Bone Cements↗
PubMed1995

Reduction of temperatures generated by the triple reamer within the femoral head.

The triple reamer is a convenient tool for reaming the proximal femur when using a sliding screw and plate device, but unnecessarily high temperatures may be generated within the femoral head while the lateral cortex is being reamed. Nineteen female patients over 60 years old were randomized to either the standard or a modified reaming technique with the triple reamer during internal fixation of proximal femoral fractures. Temperatures generated within the femoral head were measured. Results showed a mean peak temperature of 51.9 degrees C (range 42-66) using the standard method and 46.3 degrees C (range 40-52) using the modified method (P = 0.07). A significant difference (P < 0.05) was found in the duration of temperature elevation above the critical 44 degrees C (17.4s vs 5.7s), it being prolonged in the standard group. Even in this osteoporotic patient group, damaging temperatures which may contribute to the mechanical failure of fixation, are generated within the femoral head. A simple method to avoid this problem is described.

Female↗