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Biomedical subjects

G W Hall

Publications and source records attributed to G W Hall.

At least 19 recordsLinked to original sources
PubMed1999

Rate-independent characteristics of an arthroscopically implantable force probe in the human achilles tendon.

The effect of loading rate on specimen calibration was investigated for an implantable force sensor of the two-point loading variety. This variety of sensor incorporates a strain gage to measure the compressive load applied to the sensor due to tensile loading in a soft tissue specimen. The Achilles tendon in each of four human cadaveric lower extremities was instrumented with a force sensor and then loaded in tension using a materials testing machine. Each specimen was tensile tested at three different displacement rates, 0.25, 2.5 and 12.7 cm s(-1), corresponding with mean loading rates of 33.8, 513.2, and 2838.6 N s(-1), respectively. A calibration curve relating the force sensor signal and applied tendon tension was generated for each specimen/ displacement rate combination. For each specimen, calibration curves were compared by calculating an RMS error for the entire data set (eRMS = 1.6% of the full load value) and a coefficient of determination, R2, of a curve fit through all of the data (R2 = 99.6%). Over the range of rates tested, no measurable change in sensor sensitivity due to loading rate was observed. Hysteresis for all displacement rates was on the order of 2.4%.

Achilles Tendon↗
PubMed1998

Unusually severe heterozygous beta-thalassemia: evidence for an interacting gene affecting globin translation.

A common beta-thalassemia mutation in Asian populations is the C --> T substitution at position 654 of intron 2, which leads to the activation of two cryptic splicing sites and the incorporation of 73 extra nucleotides into the mutant mRNA. Like most beta-thalassemia mutations, it normally exhibits recessive inheritance. We investigated the unusually severe phenotype in two heterozygotes for this mutation, father and son, who had thalassemia intermedia and an apparent dominant mode of inheritance. An increased level of aberrantly spliced transcript in the reticulocytes of the probands compared with asymptomatic beta654 heterozygotes led us to investigate the production and processing of beta654 RNA. We showed that large amounts of the aberrant beta654 transcript were detectable in erythroblasts from one of the asymptomatic cases. The translation product of this mRNA was not detectable in vivo, and we were unable to demonstrate the translation of the mutant mRNA in a cell-free translation system. Although the reticulocyte alpha:beta mRNA ratios in the two probands were within the range observed in the asymptomatic heterozygotes, globin chain biosynthesis studies showed that the probands had considerably greater alpha:beta chain imbalance. These results imply that the more severe phenotype may be due to a second defect, possibly unlinked to the beta-globin cluster, that acts at the translational or posttranslational level.

Adult↗
PubMed1998

Beta-thalassaemia intermedia: is it possible consistently to predict phenotype from genotype?

Eighty-seven patients with beta thalassaemia of intermediate severity were investigated in our Unit to determine whether it is possible to consistently predict phenotypic severity from genotypic factors. The subjects were from the following ethnic backgrounds: Asian Indian (35.1%), Middle Eastern (24.3%), Mediterranean (21.6%), Northern European (14.9%) and South-East Asian/Chinese (4.1%). There was a wide spectrum of phenotypic severity; 49 had mild disease, 22 moderate and 16 severe disease. 22/87 patients had inherited only a single copy of a beta-thalassaemia allele, of whom 11 had also co-inherited triplicated alpha genes (alpha alpha alpha/alpha alpha or alpha alpha alpha/alpha alpha alpha) and seven had dominantly inherited beta thalassaemia. In four of the heterozygotes no explanation was found for the thalassaemia-intermedia phenotype. 65/87 patients were homozygous or compound heterozygous for 26 mutations (40 genotypes) which ranged from very mild beta+ to beta0 thalassaemia alleles. All patients with two mild or very mild beta+ thalassaemia alleles had mild to moderate disease. Although concurrent inheritance of extra alpha genes with heterozygous beta thalassaemia results in thalassaemia intermedia, the disease is mild. Co-inheritance of alpha thalassaemia as a modulating factor was not evident in this cohort of patients. Presence of the in-cis Xmn I-Ggamma site was a modulating factor but insufficient to explain the high fetal haemoglobin levels encountered. In conclusion, apart from the two categories of triplicated alpha genes with heterozygous beta thalassaemia and inheritance of mild beta+ thalassaemia alleles, it was not possible to consistently predict phenotype from alpha and beta genotypes alone, due to the influence of modulating factors, some implicated (such as inheritance of HPFH determinants) and others as yet unidentified.

Adolescent↗
PubMed1994

Nonsense codon mutations in the terminal exon of the beta-globin gene are not associated with a reduction in beta-mRNA accumulation: a mechanism for the phenotype of dominant beta-thalassemia.

We present in vivo evidence that there is no reduction in beta-mRNA accumulation in patients with nonsense codons in the terminal exon of the beta-globin gene. Using reverse transcriptase/polymerase chain reaction (RT-PCR), beta-globin cDNA was isolated from the reticulocytes of individuals heterozygous for nonsense codon mutations in exons II and III of the beta-globin gene. Clinically asymptomatic individuals heterozygous for mutations causing premature termination of translation in exon II [beta(0)39(C-T) and F/S71/72(+A)] were found to have almost no mutant beta-cDNA, whereas patients with nonsense codon mutations in exon III [beta 121(G-T) and beta 127(C-T)] with the clinical phenotype of thalassemia intermedia had comparable levels of mutant and normal beta-cDNA. Translation of the mutant beta-mRNA from patients with nonsense codon mutations in exon III would give rise to truncated beta-globin chains, which could explain the more severe phenotype seen in these individuals.

Adolescent↗
PubMed1993

Meiotic recombination in an Irish family with beta-thalassaemia.

Using the technique of allele-specific priming of the polymerase chain reaction (PCR), the C-T substitution in codon 39 was identified as the cause of beta-thalassaemia in an Irish family. Analysis of the restriction fragment length polymorphisms (RFLPs) in the beta-globin gene cluster established linkage of the beta-thalassaemia mutation to a particular beta-haplotype but indicated that a recombinational event had occurred in the paternal chromosome in the younger of two affected children. Non-paternity was excluded by DNA fingerprinting analysis with hypervariable minisatellite probes. This is the fourth case of recombination in the beta-globin gene cluster to be reported. The event has occurred 5' of the polymorphic RsaI site at position -550 bp upstream of the beta-globin gene mRNA Cap site, within the 9.1-kb region that has been shown to be a hot spot for recombination in the beta-globin gene cluster.

Base Sequence↗
PubMed1993

The construction of sutureless cataract incision and the management of corneal astigmatism.

Extrapolating information from equations that govern fluid flow, a theoretical formula is developed for a sutureless cataract incision. This theoretical formula defines the resistance of aqueous outflow as a function of three variables: length of cataract incision, the length of the scleral tunnel, the tortuosity of the outflow channel, and one constant friction factor. The nonlinear relationship of corneal incisions to length, depth, and distance from the visual axis is also examined with respect to their effect on central corneal curvature and control of astigmatism. Finite element analysis of differential equations is discussed as the most plausible technique for predicting these incisional effects.

Astigmatism↗
PubMed1993

A base substitution (T-->C) in codon 29 of the alpha 2-globin gene causes alpha thalassaemia.

We have identified three individuals of Greek or Greek Cypriot origin with an atypical form of HbH disease characterized by a severe hypochromic microcytic anaemia associated with relatively small amounts of HbH in the peripheral blood. Molecular analysis has shown that each is a compound heterozygote for a previously described mutation affecting the poly A addition signal (AATAAA-->AATAAG) and a previously undescribed mutation involving a T-->C transition in codon 29 of the alpha 2 gene causing a leucine-->proline substitution. Although this mutation would be expected to produce an unstable haemoglobin and hence a haemolytic anaemia, simple heterozygotes for the alpha 29Leu-->Pro mutation have the phenotype of alpha-thalassaemia trait.

Adult↗
PubMed1992

Beta thalassaemia in the indigenous British population.

We have analysed the molecular basis of beta-thalassaemia in 22 Anglo-Saxon individuals, all of whom were heterozygous for beta-thalassaemia except for one, who was a compound heterozygote. Using a combination of allele-specific priming of the polymerase chain reaction (PCR) and direct sequencing of genomic DNA amplified by the PCR, 20/23 beta-thalassaemic genes were characterized. Nine different mutations were identified; four are commonly found in the Mediterranean, one in Asia, one has been described previously in both Europe and Asia, and three are rare mutations associated with a dominant beta-thalassaemia phenotype. In three individuals the mutation remains uncharacterized despite sequence analysis of the beta-globin gene and its immediate flanking regions. We report our findings and discuss the diversity of these mutations.

Base Sequence↗
PubMed1991

Reduction of corneal astigmatism at cataract surgery.

We studied the effect at three months of four transverse astigmatic keratotomy incisions (TAK) performed prior to phacoemulsification in 61 eyes on corneal astigmatism. The optical zone was varied in each case depending upon the magnitude of preoperative astigmatism. The eyes were compared to 105 control eyes in which no astigmatic incisions were performed to assess the estimated effect of the TAK incisions. Keratometry readings were taken preoperatively and three months postoperatively. Surgically induced astigmatism was measured using vector corrected astigmatism. Improvement in astigmatism was reported in all three optical zone groups, but the astigmatism was undercorrected in each. No complications affecting vision were reported, indicating that TAK may be a safe way to reduce postoperative astigmatism when combined with phacoemulsification.

Adult↗
PubMed1986

Cerebral photosensitisation by haematoporphyrin derivative. Evidence for an endothelial site of action.

Exposure of the cranium to white light in mice that had been given haematoporphyrin derivative (HpD) led to a rapid onset of vasogenic cerebral oedema, cerebral necrosis, coma and death. Selectivity of the initial damage for endothelium was suggested by (a) early breakdown (less than 1 h) of the blood-brain barrier (BBB) as shown by increased permeability to Evans blue (b) separation and increased vesiculation of endothelial cells at 2 h and (c) endothelial cell pyknosis at 3--4 h in small vessels next to apparently undamaged neurones and neuroglia. There was no damage to myelin sheaths, and astrocytes showed only end-feet oedema, a reaction to exudation of protein-rich fluid. Within a few hours of illumination, most cells in the illuminated area were necrotic. Cerebral photosensitivity persisted for at least 12 weeks after a single injection of HpD. Our results suggest that the primary site of damage in the brain is the endothelium of small vessels, and that HpD remains associated with this for a remarkably long time. These findings are relevant to the mechanisms by which photodynamic therapy damages other tissues, including neoplasms, and particularly to the possible application of this treatment to brain tumours.

Animals↗
PubMed1983

Regulatory interactions among the cya, crp and pts gene products in Salmonella typhimurium.

A well-characterized set of pts deletion mutants of Salmonella typhimurium were used to re-evaluate the purported role of the PTS in the inducer exclusion process and in regulation cAMP synthesis. During the course of these studies a class of secondary mutations was isolated which suppress the inhibition of cAMP synthesis caused by pts mutations. These suppressor mutations were traced to the crp locus and tentatively designated as acr (adenylate cyclase regulation) mutations. A new model is proposed in which CRP rather than adenylate cyclase is believed to be the central regulatory element in the catabolite repression phenomenon.

Cyclic AMP↗
PubMed1982

Repression of adenylate cyclase in the genus Bordetella.

Virulent phase I strains of Bordetella pertussis synthesize the regulatory metabolite adenosine 3',5'-cyclic monophosphate (cAMP); whereas, non-virulent phase IV strains are unable to do so. These findings were confirmed and extended using additional strains of B. pertussis as well as strains of Bordetella parapertussis and Bordetella bronchiseptica. Levels of adenylate cyclase activity and subsequent cAMP production were found to correlate. High adenylate cyclase activity during exponential phase was followed by an accumulation of cAMP during late log and throughout stationary phase. Measurements obtained during the X- to C-mode transition process indicated that adenylate cyclase is subject to complete repression.

Adenylyl Cyclases↗