PubMed Health⌕ Search

Biomedical subjects

J Dove

Publications and source records attributed to J Dove.

At least 19 recordsLinked to original sources
PubMed2003

Central core disease: clinical, pathological, and genetic features.

Central core disease (CCD) is a dominantly inherited congenital myopathy allelic to malignant hyperthermia (MH) caused by mutations in the RYR1 gene on chromosome 19q13.1. Eleven individuals with RYR1 mutations are described. Four index cases showed features consistent with a congenital myopathy (hypotonia, delayed motor milestones, and skeletal abnormalities including congenital hip dislocation and scoliosis). All four cases and subsequently seven other family members were found to possess novel mutations in the RYR1 gene. The degree of disability varied from one clinically normal individual, to another who had never achieved independent ambulation (the only patient with a de novo mutation). Four cases showed a mild reduction in vital capacity, repeated nocturnal polysomnography showed hypoxaemia in one case. A variety of muscle biopsy features were found; central cores were absent in the youngest case, and the biopsy specimens from two others were more suggestive of mini-core myopathy. In all cases missense mutations in exons 101, 102, and 103 of the RYR1 gene on were found. Future laboratory diagnosis of suspected cases and family members will be less invasive and more accurate with DNA analysis. Clinicians, especially paediatricians and orthopaedic surgeons, should be aware of this disorder because of the potential risk of MH.

Adolescent↗
PubMed2002

A study of the mechanical stability of scoliosis constructs using variable numbers of sublaminar wires.

Sublaminar wiring with posterior instrumentation is one of the methods used when long fusions involving 10-12 thoracolumbar levels are required. Classically, wires are used at every consecutive level to make the construct as rigid as possible, although complications like dural tears, cerebrospinal fluid leak, and neurological deficit have been reported during their passage. We compared the mechanical stability under torsional strain of five specimens of each of three construct designs, by static and fatigue testing, using an electro-servo-hydraulic testing machine. In construct A, a contoured Hartshill rectangle was used from T2 to L2, with sublaminar wires passed at every level. In construct B, the Hartshill rectangle was wired to the spine at every alternate level. In construct C, every alternate level was wired except at the proximal end, where two consecutive levels were wired. Industrially fabricated spine models were used to prepare these constructs. The intervertebral motion within the construct was measured using the Fastrak magnetic field sensor device. On static testing, no statistically significant difference was found in the rotational displacement of the three construct designs. On fatigue testing, all samples of construct B consistently failed, with breakage of the wire at the most proximal level on the left side. But on adding additional wires to the next level (construct C), all five samples withstood fatigue testing at 300 N load to three million cycles. We conclude that wiring alternate levels instead of every level does not compromise the stability of the construct, provided that the most proximal two levels are consecutively wired. This practice would minimise the risk of dural tears and cord damage during wire passage and reduce surgical time, not to mention the economic benefits.

Biomechanical Phenomena↗
PubMed2002

The spectrum of pathology in central core disease.

Central core disease is a congenital myopathy with muscle weakness defined pathologically by the presence of extensive areas in muscle fibres that are devoid of oxidative enzyme activity. The gene responsible has been shown to be the ryanodine receptor 1 on chromosome 19q13 and mutations have now been identified in several patients. Some cases with the morphological defect remain molecularly undefined, particularly those studied before molecular studies were available. We have studied three families with congenital onset, each with a dominantly inherited mutation in a C-terminal exon of the ryanodine receptor 1. They illustrate the spectrum of pathology that can be observed in patients with the myopathic features of central core disease. We show that extensive fibrosis and fat may be present, type 1 fibre uniformity may occur in the absence of cores; cores may be central or peripheral, single or multiple; and that an appearance of multiple focal minicores might cause a diagnostic pathological dilemma. In addition, we show the value of immunocytochemistry in identifying cores, in particular the use of antibodies to desmin and gamma-filamin.

Adult↗
PubMed2002

Shared care in gastroenterology: GPs' views of open access to out-patient follow-up for patients with inflammatory bowel disease.

OBJECTIVE: The aim of this study was to ascertain GPs' views about open access to out-patient follow-up for patients with inflammatory bowel disease (IBD). METHODS: Semi-structured interviews and a postal survey were carried out in general practices in West Glamorgan UK, each with at least one IBD patient taking part in a randomized trial of open access versus routine follow-up, which has been reported elsewhere. A total of 112 GPs from 53 general practices who referred the 180 study patients to specialist gastroenterological care in Neath or Swansea were included in the study. Main outcome measures were GPs' experience of the trial; preferences between methods of out-patient follow-up; and their views about enhancing open access follow-up. RESULTS: Sixty-nine GPs from 40 practices took part in the practice-specific data collection and 91 returned 156 patient-specific questionnaires. They expressed a strong preference for open access follow-up, for both specific patients (108/156 patients) and IBD patients in general (47/69 GPs). Preference for extending open access follow-up to other chronic conditions was not so strong (21/69 GPs). A substantial number of GPs considered their experience of the trial limited (30/69), and few GPs were aware of the shared care guideline distributed before the trial started (8/69). Few GPs encountered any problems in the management of the study patients (9/69) and <50% of the GPs used a Cumulative Encounter Form (29/69) developed for the study. Most GPs were supportive of giving patients written guidelines (56/69) and establishing a gastroenterological (GI) nurse practitioner (45/69). CONCLUSIONS: Open access follow-up of patients with IBD is supported by GPs. The approach would probably be improved by the distribution of written information to patients, the establishment of a GI nurse practitioner and an integrated approach between the nurse, hospital specialist, GP and patient.

Ambulatory Care↗
PubMed2001

Temperature and pH studies of short tandem repeat systems using capillary electrophoresis at elevated pH.

The DNA secondary structure can affect the migration time and precision of DNA separations in the physical gels used in capillary electrophoresis (CE). To counteract these effects, DNA typing is performed using elevated temperatures (60 degrees C) and high concentrations (7 M) of urea. These conditions affect the precision and lifetime of the analysis. To better understand the effects of these conditions on the reproducibility of DNA migration, we examined the effects of temperature and pH on short tandem repeat (STR) analysis using the PE/ABI 310 Genetic Analyzer. Separations were performed using the Profiler + multiplex system, a set of coamplified STRs with a 4-base repeat motif, labeled at the 5'-end using fluorescent dyes. The analytical separations were obtained using a commercial buffer at pH 8 and an experimental buffer consisting of 3% hydroxyethylcellulose at pH settings ranging from 8-12. Multichannel laser-induced fluorescence detection was used. Temperatures were examined from 30-70 degrees C. The results demonstrate the fact that highly efficient separations can be carried out at alkaline pH. In addition, improvements in temperature stability were seen when compared to results at lower pH. However, high concentrations of urea were found to be necessary to achieve optimal resolution.

Alleles↗
PubMed1997

Mechanism-based inactivation of a yeast methylamine oxidase mutant: implications for the functional role of the consensus sequence surrounding topaquinone.

The copper-containing yeast methylamine oxidase E406N mutant has an altered consensus sequence surrounding the topaquinone cofactor (residue 405). The mutation has no effect on the final yield of the active-site topaquinone cofactor during biogenesis but causes the enzyme to be inactivated by substrate methylamine [Cai, D., and Klinman, J. P. (1994) Biochemistry 33, 7674-7653]. In this study we show that the inactivation leads to the formation of a covalent adduct, which has a UV/vis spectrum very similar to that of a product Schiff base, an intermediate of topaquinone-catalyzed amine oxidation reactions. The kinetic isotope effects on the second-order rate constant for the inactivation and catalytic turnover are identical, indicating that the two processes share a common intermediate that follows C_H bond cleavage. Resonance Raman spectroscopy provides direct evidence for the accumulation of a neutral product Schiff base species. Removal of excess methylamine leads to recovery of both activity and the native absorption spectrum for E406N, indicating that the cofactor in the inactivated enzyme is chemically competent for hydrolysis. The rate of the reactivation is slow, however; the shortest half-life of the inhibited E406N at 25 degrees C is 5.9 min at pH 6.15. pH effect experiments show that the inactivation and reactivation steps are controlled by a single ionizable group with a pKa of 6.9-7.1; under basic conditions, when this residue is deprotonated, the inactivation is the fastest and the half-life of the inhibited enzyme is the longest. On the basis of the available crystal structures of copper amine oxidases, we propose that a histidine residue in the dimer interface is responsible for the observed ionization. In the wild-type enzyme this histidine is kept protonated by virtue of Glu at position 406. Unlike methylamine, the larger substrates ethylamine and benzylamine give normal turnover with E406N. Disruption of structure at the subunit interface in E406N may allow a rotation of the relatively small topa-product Schiff base complex (formed from methylamine) away from the active-site base to a conformation that is incompetent toward hydrolysis.

Consensus Sequence↗
PubMed1996

Effects of age on beta adrenergic subtype activation of adenylyl cyclase in brown adipose tissue.

Thermogenesis in brown adipose tissue (BAT) is believed to be mediated mainly by beta3 adrenergic receptors. We previously demonstrated that the specific beta3 adrenergic agonist CGP-12177 increases whole body oxygen consumption and BAT GDP binding to a greater extent in young than in senescent rats. In contrast, the forskolin-induced increases were maintained with age, suggesting that early events in beta3 adrenergic signal transduction are impaired with age. To investigate whether beta1 or beta3 adrenergic function is decreased with age, we assessed beta1 and beta3 adrenergic receptor mRNA levels and the ability of beta1 and beta3 adrenergic receptors to activate adenylyl cyclase in BAT membranes from 4- and 24-month-old F-344 rats. Both beta1 and beta3 adrenergic receptor mRNA levels decreased by 50% with age. Adenylyl cyclase stimulated by the nonspecific agonist, isoproterenol, and by the specific beta3 agonist, BRL 37344, also declined by 50% with age, whereas glucagon stimulation decreased by more than 70%. The isoproterenol-stimulated adenylyl cyclase activation curves were resolved by two-site regression analysis to determine the contribution of beta1 and beta3 adrenergic receptors. The Vmax for both beta1 and beta3 adrenergic receptors decreased by 50% with age. However, stimulation of adenylyl cyclase by NaF and forskolin was also diminished by the same amount as beta adrenergic stimulation, suggesting that the activation with age may be limited by the amount of adenylyl cyclase catalytic unit rather than by receptor number. These data suggest both beta1 and beta3 adrenergic receptors and adenylyl cyclase catalytic units are deficient with age in rodent BAT.

Adenylyl Cyclases↗
PubMed1993

The selection of wires for sublaminar fixation.

The authors report a comparative biomechanical study of the suitability of four types of stainless steel wire for sublaminar fixation. Tensile and fatigue tests were performed on wires in the configuration used at surgery. They conclude that annealed 18-gauge (1.2 mm) wire should be used at each end of a scoliosis fusion, at the upper end of a lumbar fusion, and throughout for thoracolumbar fractures. Cold-worked 20-gauge (0.87 mm) wire may be used in all other situations, but the use of annealed 20-gauge wire should be restricted to the cervical spine. The authors emphasize the importance of achieving the correct balance between wire stiffness and flexibility, of care in the handling of wires, and of proper technique in achieving secure fixation.

Bone Wires↗
PubMed1993

Development of a degradable composite for orthopaedic use: mechanical evaluation of an hydroxyapatite-polyhydroxybutyrate composite material.

This study evaluates the mechanical properties of a composite material comprising polyhydroxybutyrate with hydroxyapatite added in proportions varying from 0 to 50%. Among the three methods of production, injection moulding was found to result in the most satisfactory mechanical properties. The tensile and compressive strength and the modulus of elasticity of composite produced in this way fell within the range for fresh human bone from different anatomical sites. With the additional advantages of biocompatibility, biodegradability and the potential for piezoelectric stimulation of new local bone formation, it was concluded that the injection-moulded composite material has considerable potential for use in orthopaedic surgery, both as a material to construct certain orthopaedic implants and as an alternative to corticocancellous bone graft.

Biocompatible Materials↗
PubMed1992

Functional characterization of a novel anti-B7 monoclonal antibody.

For optimal activation of T cells, binding of their T cell receptor to antigenic peptides in the context of major histocompatibility complex molecules on antigen-presenting cells (APC) is not sufficient. Accessory signals, provided by accessory cells, are needed to induce proliferation and clonal expansion of normal T cells. It has been shown previously that the B7 molecule, present on the cell surface of activated APC, can provide the second signal by binding to the CD28 molecule on T cells. Here we describe a novel anti-B7 (mAb), B7-24. This mAb binds to a functionally important epitope of the B7 molecule. Fab fragments of B7-24 can almost completely block anti-CD3-induced, B7-dependent T cell proliferation when tested in a model system where purified T cells are co-cultured with 3T6 cells expressing the human Fc gamma RII and human B7, in the presence of anti-CD3 mAb. In contrast, mAb B7-24 is not able to inhibit T cell proliferation in primary mixed lymphocyte reactions where purified T cells are co-cultured with Epstein-Barr virus-transformed B cells. These findings suggest that other cell surface molecules allow for maximal proliferation of T cells in mixed lymphocyte reactions, even when the interaction between B7 and CD28 is blocked by B7-24.

Animals↗
PubMed1991

A pedicle screw bridging device for posterior segmental fixation of the spine: preliminary mechanical testing results.

Mechanical assessment of a new pedicle screw bridge device for spinal surgery is reported. Results are given for a series of single tests to failure and a fatigue cyclical loading test. Comparative testing of torsional and lateral bending resistance on three surgical spinal fixation systems was carried out: Luque, wired Hartshill rectangle and pedicle screwed bridge with Hartshill rectangle and pedicle screwed bridge with Hartshill rectangle. The results show the superiority of the bridged Hartshill in both rotational and lateral bending resistance. The new bridge device could also improve the versatility of the Hartshill system to cover a wider spectrum of spinal fixations. A test to determine the axial pull-out strength of three screw designs was undertaken. The differences between the forces needed were insignificant. At failure a cylinder of bone tissues greater than the major diameter of the screw was pulled out without breaking the bone.

Biomechanical Phenomena↗
PubMed1991

Low back pain surgery, the use of the Hartshill system.

The Hartshill system is a modification of the Luque system of segmental spinal instrumentation. The philosophy of its use in low back pain is firstly the careful selection of patients. The method of selection will be discussed and attention will be drawn to one specific indication for low back surgery; namely, osteoarthritis of the lumbar facet joints. In any one patient the surgeon must be confident that the patient's pain is bad enough for surgery and that he has identified a definite pain source. The surgery should be designed to remove the pain source. If in the process of removing the pain source the spine is rendered unstable, then it is recommended that a fusion with internal fixation be performed. An independent review of our first 75 cases for osteoarthritis of the lumbar facet joints will be described. More recently we have recognized that in the lumbar spine it can be advantageous, particularly when there has been a wide laminectomy in the past, to gain fixation via the pedicle. The development and early clinical experience of a pedicle screw clamp to complement the Hartshill system will be described.

Back Pain↗