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Biomedical subjects

Andrew J Price

Publications and source records attributed to Andrew J Price.

5 recordsLinked to original sources

Extreme context specificity in differential allelic expression.

Variability in cis-regulation of gene expression has been implicated in the phenotypic manifestation of complex traits including common, multifactorial diseases. The differential expression of alleles due to polymorphism in cis-regulatory elements is common in the human genome, but there is a paucity of information about the context specificity of these control elements. In this study, we examined the differential allelic expression (DAE) of BMP5 in human mesenchymal tissues obtained from 16 donors undergoing joint replacement for treatment of osteoarthritis. We observed significant differences in BMP5 allelic output, with allelic ratios greater than 4:1 (P < 10(-20)) in the tissues of some donors. We also discovered a significant variability in allelic expression within the different tissues of donors. For 12 of our donors, we examined the allelic expression of BMP5 in two different regions of cartilage: cartilage adjacent to the site of the osteoarthritic lesion and cartilage distal from the lesion. Five of these 12 donors demonstrated highly significant differences (P < or = 10(-8)) in allelic expression between the different regions of their cartilage. Using DAE as a phenotype, we attempted to map tissue-specific cis-regulatory polymorphisms, and we identified a single nucleotide polymorphism located downstream of BMP5, which was significantly associated with DAE in some but not all of the examined tissues. These findings suggest that allelic expression can be highly context specific and that when interrogating the cis-regulatory control of a particular gene, one cannot necessarily assume that allelic expression is conserved across different tissues or even across different regions of the same tissue.

Alleles↗

Iron complexes of facially capping triphosphorus macrocycles.

Primary and secondary phosphine piano-stool complexes of the type [eta(5)-CpFeL3]+ (L = phenylphosphine, 3, (alpha-methyl)vinylphosphine, 4, allylphosphine, 5, (2-methylpropenyl)phosphine, 5b, allyl(phenyl)phosphine, 6) are described. The alkenyl phosphine complexes, 5 and 6, react by intramolecular hydrophosphination to give the corresponding [eta(5)-CpFe]+ complexes of 1,5,9-triphosphacyclododecane (12-aneP3R3, 2, R = H), 9 and 10 respectively. Alkylation of the secondary phosphines in 9 is achieved by hydrophosphinations with ethene to give the 12-aneP3R3 (R = Et) derivative 11. These complexes are also obtained by reaction of suitable [eta(5)-CpFe]+ containing precursor complexes with the corresponding free 12-aneP3R3 macrocycle as is the related [eta(5)-Cp*Fe]+ derivative, 8. Direct substitution of acetonitrile in [Fe(CH3CN)6][BF4]2 by 12-aneP3Et3, leads to the macrocycle piano-stool complex, [(12-aneP3Et3)Fe(CH3CN)3][BF4]2, 7. The crystal structures of selected primary phosphine, eta(5)-Cp, eta(5)-Cp* complexes and 7, allow a comparison of steric influences upon key macrocycle ring closure reactions and hence an insight into parameters required for the formation of smaller ring sizes by template based methods.

Journal Article↗

Oxford medial unicompartmental arthroplasty for focal spontaneous osteonecrosis of the knee.

BACKGROUND: Spontaneous osteonecrosis of the knee (SONK) is a distinct clinical condition occurring in patients without any associated risk factors. There is controversy as to the best method of treatment, and the available literature would suggest that patients with SONK have a worse outcome than those with primary osteoarthrosis when arthroplasty is performed. We assessed the outcome of medial unicompartmental knee arthroplasty (UKA) using the Oxford prosthesis for end-stage focal spontaneous osteonecrosis of the knee (SONK; Ahlbäck grades III and IV). PATIENTS AND METHODS: We assessed 29 knees (27 patients) with spontaneous osteonecrosis of the knee using the Oxford Knee Score. 26 knees had osteonecrosis of the medial femoral condyle and 3 had osteonecrosis of the medial tibial plateau. All had been operated on using the Oxford Medial Unicompartmental Knee Arthroplasty (UKA). This group was compared to a similar group (28 knees, 26 patients) who had undergone the same arthroplasty, but because of primary osteoarthrosis. Patients were matched for age, sex and time since operation. The mean length of follow-up was 5 (1-13) years. RESULTS: There were no implant failures in either group, but there was 1 death (from unrelated causes) 9 months after arthroplasty in the group with osteonecrosis. The mean Oxford Knee Score in the group with osteonecrosis was 38, and it was 40 in the group with osteoarthrosis. INTERPRETATION: Use of the Oxford Medial UKA for spontaneous focal osteonecrosis of the knee is reliable in the short to medium term, and gives results similar to those obtained when it is used for patients with primary osteoarthrosis.

Aged↗

Sagittal plane kinematics of a mobile-bearing unicompartmental knee arthroplasty at 10 years: a comparative in vivo fluoroscopic analysis.

This study compares in vivo sagittal plane kinematics of the Oxford mobile-bearing unicompartmental knee arthroplasty (UKA) at 1 and 10 years' postsurgery (10 knees) with a fixed-bearing total knee arthroplasty (TKA) (5 knees) and the normal knee (5 knees), using dynamic fluoroscopic measurement of the patellar tendon angle. The Oxford UKA preserved normal changes in patellar tendon angle with flexion, and this was maintained at 10 years. In contrast, an abnormal pattern was seen with the TKA. The results suggest that a normal pattern of sagittal plane knee kinematics exists following Oxford medial UKA and imply that anterior cruciate ligament function is maintained in the long term.

Adult↗

Simultaneous in vitro measurement of patellofemoral kinematics and forces.

This study involved the development and testing of a system for the simultaneous in vitro measurement of tibiofemoral kinematics and patellofemoral kinematics and forces. Knee motion was tracked using a Vicon 370, and patellofemoral force was measured using a six degree-of-freedom transducer based on the design of Singerman et al. Using this system, twelve knee specimens were tested in supine leg extension under a simulated quadriceps force. The comprehensive set of results corresponds well to the individual results of previous studies. The measurement system will be of value in assessing the effects of total knee arthroplasty on patellar function.

Biomechanical Phenomena↗