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Biomedical subjects

J Bidwell

Publications and source records attributed to J Bidwell.

At least 19 recordsLinked to original sources
PubMed2004

TNFalpha polymorphism frequencies in HPV-associated cervical dysplasia.

OBJECTIVES: Persistent high-risk HPV infection of the uterine cervix is associated with CIN and cervical carcinoma. Women with a reduced pro-inflammatory response to HPV are likely to be susceptible to viral persistence, and therefore, potentially more vulnerable to cervical neoplasia. In this study, we investigate whether nucleotide sequence polymorphisms in the TNFalpha (TNFSF2) gene (which can modify gene transcription up to 9-fold) might influence susceptibility to, or evolution of, CIN. METHODS: Induced heteroduplex analysis was used to identify polymorphisms at positions TNFalpha -308 and -238 in women with normal cervical cytology and with cervical disease. Patients with low-grade disease were HPV typed using general primer GP5+/6+ PCR/EIA and reverse line blotting, and were reassessed for disease status at 6 and 24 months. RESULTS: CIN patients as a group had a significantly higher frequency of TNFalpha -308 low-secretor genotypes (GG) compared to controls, and this effect was most pronounced in the CIN1 group (P = 0.01 and P = 0.004, respectively). TNFalpha polymorphism frequencies at position -238 were similar for patients and controls. Neither polymorphism was associated with the presence of HPV infection at recruitment or disease outcome at 6 or 24 months. CONCLUSIONS: These findings support the hypothesis that susceptibility to CIN is influenced by TNFalpha -308 polymorphism.

Female↗
PubMed2004

Identification of two novel single nucleotide polymorphisms in the promoter of the human interleukin-18 receptor alpha.

Single-strand conformational polymorphism (SSCP) was used to identify single nucleotide polymorphisms (SNPs) in the promoter region of the human interleukin-18 receptor alpha (IL-18Ralpha). Two SNPs were identified at positions -69 and -638 relative to the transcriptional start site. Two-way comparison of the two SNPs revealed strong linkage disequilibrium (chi2 = 63.45, P < 0.001). Three haplotypes were identified, namely C-69C-638, T-69C-638 and C-69T-638, with frequencies of 0.26, 0.39 and 0.35, respectively.

Alleles↗
PubMed2002

Review of the potential use of brown algal ecotoxicological assays in monitoring effluent discharge and pollution in southern Australia.

The temperate near-shore reefs of southern Australasia possess diverse assemblages of brown algal macrophytes which underpin major grazing and detrital food chains in medium to high energy coastal habitats. These 'kelp' communities are at risk from effluent discharge with documented decline of macrophyte stands in areas subject to outfall. Recent studies utilising reproductive endpoints of several Australian species in ecotoxicological assays have highlighted their sensitivity to pollution. Results indicate an acceptable degree of reproducibility for assays with variation in response between taxa presumably related to differing habitat requirements and potential for stress resulting from toxicant/pollution exposure. Species studied are drawn from the orders Laminariales and Fucales, with the latter in particular offering substantial scope for further investigation. The greatest diversity of fucoid algae is found in south-eastern Australia and closely related taxa occur in similar latitudes in both the southern and northern hemispheres. The broad distribution of taxa from both taxonomic groups enables ready comparison of assays from disparate locations and offers the potential for simple, routine toxicological testing and habitat monitoring across broad geographic ranges.

Australia↗
PubMed2001

A comparison of the findings of wrist arthroscopy and magnetic resonance imaging in the investigation of wrist pain.

Between 1996 and 1999, 54 patients with wrist pain had magnetic resonance imaging performed using a 1.5 Tesla scanner without a wrist coil. Wrist arthroscopy was performed using a standard technique. The findings were then compared. Magnetic resonance imaging had a low sensitivity for the detection of triangular fibrocartilage complex injuries (0.44) and scapholunate ligament injuries (0.11) when wrist arthroscopy was used as the standard of reference. We conclude that when a magnetoresonance technique that does not employ a dedicated wrist coil is used, a negative magnetic resonance imaging scan does not exclude these two significant injuries.

Arthroscopy↗
PubMed1999

An association between LSIL and the high secretor phenotype of IL-1beta.

OBJECTIVE: The aims of this study were to determine the frequency of a nucleotide transition from C to T, which leads to increased transcription of interleukin-1beta (IL-1beta) in patients with different grades of cervical lesions, and to determine whether a correlation exists between the genotypes and cervical lesions. METHODS: One hundred forty-seven DNA samples from patients with different grades of cervical lesions were compared with 100 healthy, age and sex-matched bone marrow donors. TaqI restriction digest of PCR products was used to analyze the IL-1beta +5887 C --> T mutation and the results were confirmed using induced heteroduplex analysis with an induced heteroduplex generator. RESULTS: The Pearson chi2 test (Yate's correction) was used for statistical analysis. Patients with LSIL (n = 80) demonstrated a high frequency of allele T, previously associated with high IL-1beta secretor phenotype, compared to controls (P = 0.000012). A trend was also observed in patients with HSIL (n = 28, P = 0.039). CONCLUSIONS: We report for the first time a highly significant association between high secretor IL-1beta phenotypes (i.e., IL-1beta +5887 CT or TT genotypes) and LSIL. A less significant association exists with HSIL. The intrinsic ability to produce variable amounts of IL-1beta during different clinical stages involving cervical lesions may be of immunological importance in their pathogenesis.

Adenocarcinoma↗
PubMed1999

Identification of novel single nucleotide polymorphisms in intron 1B and exon 1C of the human interleukin-1 receptor type I (IL-1RI) gene.

We have identified two novel single nucleotide polymorphisms in the 5' region of the human IL-1RI gene: (1) A-->G at position 52 in intron 1B (GenBank accession number AF146426), which creates an Mspl restriction endonuclease site. Allele frequencies in a Caucasian population were 0.1 (A allele) and 0.9 (G allele). (2) A-->T at position 140 in exon 1C (GenBank accession number AF146427). Allele frequencies in a Caucasian population were 0.27 (A allele) and 0.73 (T allele).

Base Sequence↗
PubMed1999

A bi-allelic VNTR in the human TNFR2 (p75) gene promoter.

We describe a bi-allelic VNTR polymorphism within a 42 bp region in the promoter of the tumour necrosis factor receptor 2 gene (TNFR2). Within this region there are one (Allele 1) or two (Allele 2) repeats of a 15 bp sequence, 5'-GCCGGGC AGGTGGAG-3'. Allele frequencies observed in a Caucasian population were 0.3 (Allele 1) and 0.7 (Allele 2).

Alleles↗
PubMed1999

Cytokine gene polymorphism in human disease: on-line databases.

The pathologies of many infectious, autoimmune and malignant diseases are influenced by the profiles of cytokine production in pro-inflammatory (TH1) and anti-inflammatory (TH2) T cells. Interindividual differences in cytokine profiles appear to be due, at least in part, to allelic polymorphism within regulatory regions of cytokine gene. Many studies have examined the relationship between cytokine gene polymorphism, cytokine gene expression in vitro, and the susceptibility to and clinical severity of diseases. A review of the findings of these studies is presented. An on-line version featuring appropriate updates is accessible from the World Wide Web site, http://www.pam.bris.ac.uk/services/GAI/cytokine4.htm.

Cytokines↗
PubMed1999

Fulcrum for the future: the creation of a values-driven culture.

This article describes the efforts of a small children's specialty hospital to prepare for a difficult period of restructuring in the marketplace by using the organization's core values as a force for direction, stabilization, and leverage. A best practices model was used to identify values that were a central part of the hospital's cultural heritage but were also critical for ensuring future institutional success. Principles for values definition and implementation provide guidance for other health care institutions.

Child↗
PubMed1998

Analysis of differential gene expression in rat tibia after an osteogenic stimulus in vivo: mechanical loading regulates osteopontin and myeloperoxidase.

The skeleton has the ability to alter its mass, geometry, and strength in response to mechanical stress. In order to elucidate the molecular mechanisms underlying this phenomenon, differential display reverse transcriptase-polymerase chain reaction (DDRT-PCR) was used to analyze gene expression in endocortical bone of mature female rats. Female Sprague-Dawley rats, approximately 8 months old, received either a sham or bending load using a four-point loading apparatus on the right tibia. RNA was collected at 1 h and 24 h after load was applied, reverse-transcribed into cDNA, and used in DDRT-PCR. Parallel display of samples from sham and loaded bones on a sequencing gel showed several regulated bands. Further analysis of seven of these bands allowed us to isolate two genes that are regulated in response to a loading stimulus. Nucleotide analysis showed that one of the differentially expressed bands shares 99% sequence identity with rat osteopontin (OPN), a noncollagenous bone matrix protein. Northern blot analysis confirms that OPN mRNA expression is increased by nearly 4-fold, at 6 h and 24 h after loading. The second band shares 90% homology with mouse myeloperoxidase (MPO), a bactericidal enzyme found primarily in neutrophils and monocytes. Semiquantitative PCR confirms that MPO expression is decreased 4- to 10-fold, at 1 h and 24 h after loading. Tissue distribution analysis confirmed MPO expression in bone but not in other tissues examined. In vitro analysis showed that MPO expression was not detectable in total RNA from UMR 106 osteoblastic cells or in confluent primary cultures of osteoblasts derived from either rat primary spongiosa or diaphyseal marrow. Database analysis suggests that MPO is expressed by osteocytes. These findings reinforce the association of OPN expression to bone turnover and describes for the first time, decreased expression of MPO during load-induced bone formation. These results suggest a role for both OPN and MPO expression in bone cell function.

Animals↗
PubMed1998

Rapid genotypic diagnosis of type 2A von Willebrand's disease by heteroduplex analysis.

We have previously reported a rapid heteroduplex-based technique which is able to identify at least 10 recurrent mutations associated with type 2A von Willebrand's disease. Thirteen patients with this disorder were genotyped by this method and a specific mutation was identified in nine cases. This simple DNA based approach can provide useful information to support data derived from phenotype tests in the initial assessment of such patients.

DNA↗
PubMed1998

Type 2N von Willebrand disease: rapid genetic diagnosis of G2811A (R854Q), C2696T (R816W), T2701A (H817Q) and G2823T (C858F)--detection of a novel candidate type 2N mutation: C2810T (R854W).

The majority of patients with type 2N von Willebrand disease (VWD type 2N) have mutations in the region of the von Willebrand factor (VWF) gene encoding the factor VIII binding domain of VWF. Two mutations predominate among VWD type 2N patients: G2811A and C2696T, which respectively bring about the amino acid substitutions R854Q and R816W in VWF. Several other mutations have been found in VWD type 2N, including T2701A (H817Q) and G2823T (C858F). We have developed a genetic test which permits rapid screening for these four mutations in a single polymerase chain reaction (PCR). The test employs induced heteroduplex formation using two universal heteroduplex generators, one of which detects G2811A (R854Q) and G2823T (C858F), the other detects C2696T (R816W) and T2701A (H817Q). The allele frequency of the common G2811A (R854Q) mutation was investigated in the local (S. Wales) population by examination of 216 VWF genes (108 individuals) and was found to be 0.01. The heteroduplex-based test additionally detected a novel candidate type 2N mutation, C2810T (R854W) and a previously described polymorphism, G2805A (R852Q). The polymorphism showed allele frequencies of 0.92 (G nucleotide) and 0.08 (A nucleotide) in the population study.

Base Sequence↗
PubMed1997

Parathyroid hormone (1-34)-mediated interleukin-6 induction.

Parathyroid hormone (PTH) functions in part by regulating osteoblast cytokine expression. We recently demonstrated that PTH induced a rapid and transient increase in interleukin-6 (IL-6) mRNA expression in rat bones in vivo. To determine the molecular basis of this effect, we analyzed the human IL-6 promoter fused (-1,179 to +9) with the chloramphenicol acetyltransferase (CAT) reporter gene in stable transfections into human osteoblast-like osteosarcoma SaOS-2 cells. We compared the effects of PTH on IL-6 expression with adenylate cyclase activator forskolin, PKC activator phorbol 12-myristate 13-acetate (PMA), calcium ionophore A23187, interleukin-1 alpha (IL-1 alpha), prostaglandin E-2 (PGE-2), RS-66271 (a parathyroid hormone-related peptide analog), and platelet-derived growth factor-BB (PDGF-BB). Analyses of cell clones showed that IL-6 promoter expression was extremely low in the unstimulated state. Exposure to PTH (0.001-100 nM) for 12 h stimulated CAT expression in a dose-dependent manner (200-500% of control). Treatment with IL-1 alpha was more potent than PTH in inducing transcription of the IL-6 promoter (900-1,000%). Activation of the cAMP-PKA pathway by treatment with forskolin induced a comparable level of induction with PTH. Together, the effects of PTH and forskolin were additive. RS-66271, previously shown to have PTH-like effects, induced a comparable level of IL-6 promoter expression. When examined together, PTH+RS-66271 effects were comparable to PTH effects alone. Exposure to PGE-2, PMA, PDGF-BB, or A23187 for 12 h did not significantly alter IL-6 promoter expression. These results demonstrate PTH, forskolin, the PTHrP analog RS-66271, and IL-1 alpha stimulate IL-6 expression by stimulating gene transcription. The response to forskolin suggests that the messenger system mediated by PKA is sufficient to induce IL-6 expression.

Becaplermin↗
PubMed1997

Simultaneous genotyping for all three known structural mutations in the human mannose-binding lectin gene.

We describe a rapid and simple method for genotyping the three known structural mutations within exon 1 of the mannan-binding lectin (MBL) gene. A PCR-amplifiable synthetic DNA (Universal Heteroduplex Generator) was annealed to genomic PCR product from exon 1 to generate unique DNA heteroduplexes for each mutation. Heteroduplexes were then resolved by non-denaturing polyacrylamide gel electrophoresis. The technique was initially validated with previously typed samples and then applied to previously untyped samples with the results confirmed by DNA sequencing.

Amino Acid Sequence↗