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Biomedical subjects

G R Taylor

Publications and source records attributed to G R Taylor.

At least 19 recordsLinked to original sources
PubMed2005

Flexible intramedullary nailing of displaced diaphyseal forearm fractures in children.

INTRODUCTION: This study analyses the results of 50 displaced diaphyseal forearm fractures in children treated with flexible intramedullary nailing. METHODS: Between 1999 and 2002 we treated 50 children aged between 5 and 15 years, with diaphyseal fractures of the forearm using Flexible intramedullary nailing (FIN). Both bones were fractures in 45 patients, radius only in 4 and ulna only in 1. The indications for fixation were instability (26), re-displacement (20), and open fractures (4). RESULTS: 24 patients were reduced closed, followed by nailing, while 26 fractures required open reduction of either one bone(16 cases) or both bones(10 cases) prior to nailing. Bony union of all fractures was achieved by an average of 7 weeks (range 6 weeks to 4 months) with one delayed union. Pronation was restricted by an average of 20 degrees in 9 patients. Two patients developed post operative compartment syndrome requiring fasciotomy. Three patients were lost to follow-up. INTERPRETATION: FIN led to early bony union with acceptable bony alignment in all 47 patients available at final follow-up. We therefore recommend FIN for the treatment of unstable diaphyseal forearm fractures in children.

Adolescent↗
PubMed2005

Complex pediatric elbow injury: an uncommon case.

BACKGROUND: There is paucity of literature describing complex elbow trauma in the pediatric population. We described a case of an uncommon pediatric elbow injury comprised of lateral condyle fracture associated with posterolateral dislocation of elbow. CASE PRESENTATION: A 12-year-old boy sustained a direct elbow trauma and presented with Milch type II lateral condyle fracture associated with posterolateral dislocation of elbow. Elbow dislocation was managed by closed reduction. The elbow stability was assessed under general anaesthesia, followed by open K-wiring for the lateral condylar fracture fixation. The patient had an uneventful recovery with an excellent outcome at 39 months follow-up. CONCLUSION: Complex pediatric elbow injuries are quite unusual to encounter, the management of such fractures can be technically demanding. Concomitant elbow dislocation should be managed by closed reduction followed by open reduction and internal fixation (K-wires or cannulated screws) of the lateral condyle fracture.

Bone Wires↗
PubMed2003

Isolation of a rhabdovirus during outbreaks of disease in cyprinid fish species at fishery sites in England.

A virus was isolated during disease outbreaks in bream Abramis brama, tench Tinca tinca, roach Rutilis rutilis and crucian carp Carassius carassius populations at 6 fishery sites in England in 1999. Mortalities at the sites were primarily among recently introduced fish and the predominant fish species affected was bream. The bream stocked at 5 of the 6 English fishery sites were found to have originated from the River Bann, Northern Ireland. Most fish presented few consistent external signs of disease but some exhibited clinical signs similar to those of spring viraemia of carp (SVC), with extensive skin haemorrhages, ulceration on the flanks and internal signs including ascites and petechial haemorrhages. The most prominent histopathological changes were hepatocellular necrosis, interstitial nephritis and splenitis. The virus induced a cytopathic effect in tissue cultures (Epithelioma papulosum cyprini [EPC] cells) at 20 degrees C and produced moderate signals in an enzyme immunoassay (EIA) for the detection of SVC virus. The virus showed a close serological relationship to pike fry rhabdovirus in both EIA and serum neutralisation assays and to a rhabdovirus isolated during a disease outbreak in a bream population in the River Bann in 1998. A high degree of sequence similarity (> or = 99.5% nucleotide identity) was observed between the English isolates and those from the River Bann. Experimental infection of juvenile bream, tench and carp with EPC cell-grown rhabdovirus by bath and intraperitoneal injection resulted in a 40% mortality of bream in the injection group only. The virus was re-isolated from pooled kidney, liver and spleen tissue samples from moribund bream. The field observations together with the experimental results indicate that this rhabdovirus is of low virulence but may have the potential to cause significant mortality in fishes under stress.

Animals↗
PubMed2003

Nucleotide sequence analysis of the glycoprotein gene of putative spring viraemia of carp virus and pike fry rhabdovirus isolates reveals four genogroups.

RT-PCR methods have been applied to the detection and sequencing of the glycoprotein gene of putative spring viraemia of carp viruses (SVCV) and pike fry rhabdoviruses (PFRV), including isolates from tench, grass carp, roach, bream and false harlequin, sheatfish and orfe. Phylogenetic analysis of a 550 nucleotide (nt) region of the glycoprotein gene identified 4 groups, I to IV. Significantly, the majority of viruses previously identified as PFRV formed a distinct cluster (Genogroup IV) which shared <80% nucleotide identity with the PFRV reference strain (Genogroup III). The similarity between another PFRV-like virus isolated from grass carp and representatives of Genogroups III and IV was also <80%, indicating that this virus belonged to a third group (Genogroup II). All of the putative SVC viruses were assigned to a 4th group (Genogroup I), sharing <61% nucleotide identity with viruses in Genogroups II to IV.

Amino Acid Sequence↗
PubMed2003

Genomic deletions in MSH2 or MLH1 are a frequent cause of hereditary non-polyposis colorectal cancer: identification of novel and recurrent deletions by MLPA.

Gene dosage abnormalities account for a significant proportion of the mutations in genes tested in DNA diagnostic laboratories. Detection of these changes has proved a challenge as the methods available to date are time consuming or unreliable. The multiplex ligation-dependent probe assay (MLPA) is a new technique allowing relative quantification of up to 40 different nucleic acid sequences in a single reaction tube. We have evaluated MLPA for potential use in the diagnostic setting against the following criteria: accuracy, reagent cost, hands-on time, reliability, and retests required. A total of 215 UK patients referred for genetic testing on the basis of a family history consistent with autosomal dominant hereditary non-polyposis colorectal cancer (HNPCC or Lynch syndrome) were tested by MLPA. Of these, 12 cases with deletions of one or more exons were identified, six with MLH1 deletions and six with MSH2 deletions. Test failure rates were less than 5% and overall mutation detection sensitivity in this series was increased by approximately 50% by the inclusion of MLPA for an additional testing cost of about 10%. Two novel mutations in MSH2 and 10 novel point mutations in MLH1 were also identified during the course of this study. We conclude that MLPA is a cost effective and robust gene dosage method that can be readily adopted by diagnostic services. Comprehensive mutation scanning for MSH2 and MLH1 is incomplete without gene dosage analysis.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Investigations on a clinically and functionally unusual and novel germline p53 mutation.

This report describes an individual with a rare choroid plexus papilloma in adulthood (age 29) after earlier having an osteosarcoma (age 22). The results from this study, and others, suggest that it may be advisable to consider the possibility of a germline p53 mutation in adults presenting with choroid plexus tumours. In the current study automated DNA sequencing of genomic DNA detected a novel germline 7 base pair insertion in exon 5 of the p53 gene in this patient. The alteration in frame would produce amino acid substitutions beginning with alanine to glycine at position 161 and a stop codon at position 182 in the mutated protein. Surprisingly two assays of p53 function gave apparently wild-type results on peripheral blood lymphocytes from this individual. These results led us to carry out more detailed functional tests on the mutant protein. The mutant allele was expressed either at very low levels or not at all in phytohaemagglutinin stimulated lymphocytes. Further, the mutant protein was completely non-functional in terms of its ability to transactivate a series of p53-responsive genes (p21(WAF1), bax, PIG3), to transrepress a target gene and to inhibit colony growth in transfected Saos-2 cells. However, surprisingly, data from irradiated peripheral blood lymphocytes and transfected Saos-2 cells, suggested that this truncated, mutant protein retains significant ability to induce apoptosis.

Adult↗
PubMed2002

The detection of large deletions or duplications in genomic DNA.

While methods for the detection of point mutations and small insertions or deletions in genomic DNA are well established, the detection of larger (>100 bp) genomic duplications or deletions can be more difficult. Most mutation scanning methods use PCR as a first step, but the subsequent analyses are usually qualitative rather than quantitative. Gene dosage methods based on PCR need to be quantitative (i.e., they should report molar quantities of starting material) or semi-quantitative (i.e., they should report gene dosage relative to an internal standard). Without some sort of quantitation, heterozygous deletions and duplications may be overlooked and therefore be under-ascertained. Gene dosage methods provide the additional benefit of reporting allele drop-out in the PCR. This could impact on SNP surveys, where large-scale genotyping may miss null alleles. Here we review recent developments in techniques for the detection of this type of mutation and compare their relative strengths and weaknesses. We emphasize that comprehensive mutation analysis should include scanning for large insertions and deletions and duplications.

Blotting, Southern↗
PubMed2001

Genetic analysis of the connexin-26 M34T variant: identification of genotype M34T/M34T segregating with mild-moderate non-syndromic sensorineural hearing loss.

Mutations in the human gap junction beta-2 gene (GJB2) that encodes connexin-26 have been shown to cause non-syndromic sensorineural hearing loss (NSSNHL) at the DFNB1 locus on 13q11. Functional and genetic data regarding the disease causing potential of one particular GJB2 sequence variant, 101 T-->C (M34T), have proven contradictory. In this study, we found the prevalence of the M34T allele in a cohort of white sib pairs and sporadic cases with NSSNHL from the United Kingdom and Ireland to be 3.179% of chromosomes screened. Significantly, we identified the first M34T/M34T genotype cosegregating in a single family with mid to high frequency NSSNHL. Screening a control population of 630 subjects we identified 25 M34T heterozygotes; however, no M34T homozygotes were detected. Surprisingly, the majority of M34T alleles (88%) were in cis with a 10 bp deletion in the 5' non-coding sequence. This non-coding deletion was also homozygous in the homozygous M34T subjects. Microsatellite analysis of flanking loci in M34T heterozygotes and controls does not define an extensive ancestral haplotype but preliminary data suggest two common alleles in subjects with the M34T allele. In summary, we provide data that support M34T acting as a recessive GJB2 allele associated with mild-moderate prelingual hearing impairment.

Alleles↗
PubMed2001

A comparison of methods for gene dosage analysis in HMSN type 1.

A number of different approaches are used in diagnostic laboratories to detect the 1.5 Mb duplication at 17p11.2 seen in approximately 70% of patients with hereditary motor and sensory neuropathy type 1 (HMSN1). Here we compare the methods used in UK diagnostic laboratories to detect the duplication. Samples referred to participating centres for HMSN testing were collected, randomised, and distributed for testing. One hundred samples were examined using five different methods; each method was tested by two independent laboratories. Identical results were obtained from all laboratories for 44 samples. The remaining samples were classified as duplication positive or duplication negative on the basis of the same result by two or more methods. A total of 95 samples were classified by more than one method, two were withdrawn from the study as the same result was not obtained by two methods, and three are thought to have a duplication smaller than 1.5 Mb. Seven of 49 duplications were not detected by methods used to detect the common junction fragment and the use of microsatellites failed to yield a result in four of 95 samples. Sequence tagged site (STS) dosage analysis was found to be the most sensitive of the methods tested, although this method was found to be the most likely to require repeat analysis. Eight samples gave discordant results between the two laboratories testing by the same method. Upon retesting, reasons for the initial incorrect result included processing and typographical errors.

Charcot-Marie-Tooth Disease↗
PubMed2001

A common founder for the 35delG GJB2 gene mutation in connexin 26 hearing impairment.

Fifty to eighty percent of autosomal recessive congenital severe to profound hearing impairment result from mutations in a single gene, GJB2, that encodes the protein connexin 26. One mutation of this gene, the 35delG allele, is particularly common in white populations. We report evidence that the high frequency of this allelic variant is the result of a founder effect rather than a mutational hot spot in GJB2, which was the prevailing hypothesis. Patients homozygous for the 35delG mutation and normal hearing controls originating from Belgium, the UK, and the USA were genotyped for different single nucleotide polymorphisms (SNPs). Four SNPs mapped in the immediate vicinity of GJB2, while two were positioned up to 76 kb from it. Significant differences between the genotypes of patients and controls for the five SNPs closest to GJB2 were found, with nearly complete association of one SNP allele with the 35delG mutation. For the most remote SNP, we could not detect any association. We conclude that the 35delG mutation is derived from a common, albeit ancient founder.

Alleles↗
PubMed2000

A comparison of fluorescent SSCP and denaturing HPLC for high throughput mutation scanning.

We examined 67 different mutations in 16 different amplicons in a comparison of mutation detection by fluorescent single strand conformation polymorphism (F-SSCP) and by denaturing HPLC (DHPLC). F-SSCP was used to analyze fluorescent amplicons with internal size standards and automated fragment analysis (GeneScan, PE Applied Biosystems, Foster City, CA). In DHPLC, unlabelled amplicons were analyzed by reverse phase HPLC with fragment detection by absorbance at 260nm. Both methods had high sensitivity (95-100%) and specificity (100%). Overall, F-SSCP with external temperature control was the more sensitive method, but DHPLC was particularly useful for the rapid analysis of novel fragments.

Chromatography, High Pressure Liquid↗
PubMed2000

Exon deletions and duplications in BRCA1 detected by semiquantitative PCR.

rearrangements have recently been identified in the BRCA1 gene. Inclusion of a method for identifying such rearrangements should now be a prerequisite for providing a comprehensive mutation detection strategy. We have developed a semiquantitative PCR-based fluorescent assay for the detection of previously identified deletions. This method avoids the need for long PCR or Southern blotting and is suitable for large-scale epidemiological studies. The assay was used to screen 44 high-risk families within the U.K. Yorkshire Health Region. No deletions were detected, but five cases (11%) with an apparent duplication of exon 13 in BRCA1 were identified. The presence of this mutation was confirmed by long PCR. Further developments include extending the assay to include all exons of BRCA1.

BRCA1 Protein↗
PubMed1999

Congenital non-syndromal sensorineural hearing impairment due to connexin 26 gene mutations--molecular and audiological findings.

We screened DNA from 72 sibships and 138 sporadically affected individuals with congenital non-syndromal sensorineural hearing impairment (NSSNHI) for mutations in the 26 (CX26) gene. A total of 20 (27.8%) of the sibships and 11 (7.9%) of the sporadically affected individuals were homozygous or compound heterozygotes for CX26 mutations. A total of 11 (17.2%) of 64 individuals with severe and 30 (30%) of 100 with profound NSSNHI compared to eight (8.7%) of 92 persons with moderate and none (0%) of 19 individuals with mild hearing impairment were homozygous or compound heterozygotes for CX26 mutations (chi2 test, 3 df, P = 0.000). CX26 mutation status bad no effect on the symmetry of the hearing impairment or configuration of the audiogram. In addition, serial audiograms showed no evidence of progression of the hearing impairment or differences in the severity of the hearing impairment in affected siblings in persons whether or not due to CX26 mutations. Sporadically affected individuals with congenital NSSNHI should be routinely tested for mutations in CX26, especially if the hearing impairment is severe or profound in severity, since identification of a mutation in CX26 allows use of Mendelian recurrence risks.

Audiometry, Pure-Tone↗
PubMed1999

Enzymatic and chemical cleavage methods.

Cleavage-based methods of mutation detection offer a simple and intuitive means to detect and in most cases locate mutations within DNA fragment sizes ranging from 500 to 1500 bases. Their main advantages as a presequencing screening technology when scanning for unknown mutations is the potential to increase throughput by multiplexing. Combined with lower reagent costs per sample, mutation scanning methods offer significant advantages over currently available sequencing techniques and are likely to be of increasing importance as genomic sequence data becomes more readily available. Although enzymatic methods offer the advantages of simpler and less hazardous protocols, at present the most robust cleavage methods are based around chemical methods.

Endodeoxyribonucleases↗