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Biomedical subjects

R G Jones

Publications and source records attributed to R G Jones.

At least 37 records · Page 2Linked to original sources
PubMed1999

Signals involved in thymocyte positive and negative selection.

Extensive research has focused upon understanding how thymocytes distinguish between interactions that lead to positive or negative selection. Various intracellular pathways that are activated after TCR engagement are outlined in this review, and their contribution to thymocyte selection is discussed. Although thymocyte fate is generally governed by a quantitative/avidity model, this largely reflects the interactions that occur at the cell surface. Therefore, we outline possible models of how different intercellular interactions are translated into intracellular signals that diverge and lead to thymocyte survival or death.

Animals↗
PubMed1999

The effects of specific antibody fragments on the 'irreversible' neurotoxicity induced by Brown snake (Pseudonaja) venom.

Brown snake (Pseudonaja) venom has been reported to produce 'irreversible' post synaptic neurotoxicity (Harris & Maltin, 1981; Barnett et al., 1980). A murine phrenic nerve/diaphragm preparation was used to study the neurotoxic effects of this venom and pre- and post-synaptic components were distinguished by varying the temperature and frequency of nerve stimulation. There were no myotoxic effects and the neurotoxicity proved irreversible by washing alone. The effects of a new Fab based ovine antivenom have been investigated and proved able to produce a complete, rapid (< 1 h) reversal of the neurotoxicity induced by Brown snake venom. A reversal was also possible when the antivenom addition was delayed for a further 60 min. We believe that this is the first time such a reversal has been shown.

Animals↗
PubMed1999

A novel Fab-based antivenom for the treatment of mass bee attacks.

The frequency of mass bee attacks has dramatically increased in the Americas following the introduction and spread of the aggressive Africanized 'killer' bee (Apis mellifera scutellata). As yet no specific therapy is available, which led us to develop an ovine Fab-based antivenom as a potential new treatment. Sera from sheep immunized against the venom contained high levels of specific antibodies, as demonstrated by ELISA and by small-scale affinity chromatography, against both whole (A. m. mellifera) venom and purified melittin. A nerve muscle preparation was used to show the myotoxic effects of the venom and neutralization by the antivenom. Antivenom neutralizing ability was also demonstrated using assays for venom phospholipase A2 and in vivo activities. Venom from both European and Africanized bees appeared identical when analyzed by acid-urea gel electrophoresis. This antivenom may therefore provide the first specific therapy for the treatment of mass envenomation by either European or Africanized 'killer' bees.

Animals↗
PubMed1998

X-ray crystal structure of C3d: a C3 fragment and ligand for complement receptor 2.

Activation and covalent attachment of complement component C3 to pathogens is the key step in complement-mediated host defense. Additionally, the antigen-bound C3d fragment interacts with complement receptor 2 (CR2; also known as CD21) on B cells and thereby contributes to the initiation of an acquired humoral response. The x-ray crystal structure of human C3d solved at 2.0 angstroms resolution reveals an alpha-alpha barrel with the residues responsible for thioester formation and covalent attachment at one end and an acidic pocket at the other. The structure supports a model whereby the transition of native C3 to its functionally active state involves the disruption of a complementary domain interface and provides insight into the basis for the interaction between C3d and CR2.

Amino Acid Sequence↗
PubMed1998

Chromosome 22qII deletions. An under-recognised cause of idiopathic learning disability.

BACKGROUND: Velo-cardio-facial syndrome (VCFS), a syndrome of multiple congenital abnormalities including characteristic dysmorphology, congenital heart defects and learning disability, is associated with small interstitial deletions of chromosome 22qII. We tested the hypothesis that VCFS may be significantly under-diagnosed by screening a learning disabled population for chromosome 22qII deletions. METHOD: Two hundred and sixty-five people with learning disability residing in two learning disability hospitals in South Wales were reviewed. They were selected for inclusion in the study if they fulfilled any of the following criteria: psychotic disorder (schizophrenia or affective disorder), family history of psychotic disorder, cleft palate and/or lip, congenital heart disease, broadly defined facial dysmorphism or a history of hypocalcaemia. Fluorescence in situ hybridisation studies were performed on 74 selected individuals. RESULTS: Cytogenetic analysis revealed that two people demonstrated a previously undetected chromosome 22qII deletion. A third person demonstrated a previously undetected cytogenetically visible deletion on chromosome 15. CONCLUSIONS: VCFS appears to be aetiologically significant in a proportion of individuals with idiopathic learning disability, especially in those where psychosis is associated with mild learning disability. We suggest that clinicians should consider a chromosome 22qII deletion in people who meet selection criteria.

Adult↗
PubMed1997

Paradoxical enhancement of atherosclerosis by probucol treatment in apolipoprotein E-deficient mice.

Dietary administration of probucol (0.5%, wt/wt) efficiently reduced total plasma cholesterol levels in apolipoprotein E-deficient mice (apoE-/-) by 40%, with decreases in high density lipoprotein (HDL) and apoAI by 70 and 50%, respectively. Paradoxically, however, aortic atherosclerotic plaques in the probucol-treated apoE-/- mice formed more rapidly than in the untreated apoE-/- mice, and the lesions were two to four times larger and more mature regardless of sex, age, and genetic background (P < 10(-)6). Histologically, lesions in probucol-treated mice contained increased fibrous materials and cells other than foam cells, and were commonly associated with focal inflammation and aneurysmal dilatation. Probucol treatment also accelerated lesion development in apoE+/- mice fed an atherogenic diet, indicating that the adverse effect is not dependent on the complete absence of apoE. Furthermore, mice lacking apoE and apoAI have plasma lipoprotein profiles very similar to the probucol-treated apoE-/- mice, but do not have accelerated plaque development. Thus, the enhanced atherosclerosis in the probucol-treated animals is unlikely to be caused by the reduction of HDL and apoAI levels. Our data indicate that a reduction in plasma cholesterol caused by probucol does not necessarily lead to an antiatherogenic effect.

Animals↗
PubMed1997

A randomized control trial of an opportunistic health screening tool in primary care for people with intellectual disability.

People with intellectual disability have an increased variety of health care problems compared with the general population. The transition of care for such people from institutions into the community places them in a primary care system already facing increasing demands for their services. There is a consensus that health screening is at its most useful in identifying functional disabilities. Therefore, an intervention which helps the general practitioner (GP) towards opportunistically checking those areas of health most often deficient in people with intellectual disability would appear of considerable benefit (especially if information directing the GP towards appropriate secondary care services is also provided). The present study was designed to evaluate the impact of such an intervention.

Adolescent↗
PubMed1997

Assessment of renal osteodystrophy in dialysis patients: use of bone alkaline phosphatase, bone mineral density and parathyroid ultrasound in comparison with bone histology.

Bone biopsies were studied in 73 patients to determine if a two-site radioimmunometric assay for serum bone alkaline phosphatase (BAP), total serum alkaline phosphatase (ALP), serum intact parathyroid hormone (iPTH), hand X-rays, regional bone mineral density (BMD) measurements and parathyroid enlargement detected by ultrasonography could accurately predict renal osteodystrophy. In the patients studied 57 had hyperparathyroid bone disease, 4 mixed renal osteodystrophy, 3 adynamic bone disease, 1 osteomalacia and 8 normal histology. Serum BAP, ALP and iPTH correlated positively with mineral apposition rate, osteoblastic, osteoid and eroded surface. In the diagnosis of hyperparathyroid bone disease serum iPTH was the most sensitive investigation, detecting 81% of patients at a level > 100 pg/ml but with a specificity of only 66%. Serum BAP was more sensitive, 70% at a level of > 10 ng/ml, than serum total ALP, 30% at a level of 300 IU/l, with similar specificities, 92 and 100%, respectively. Ultrasound detection of an enlarged parathyroid gland had a sensitivity of 64% and a specificity of 100% for the diagnosis of hyperparathyroid bone disease. Hand X-rays had a poor sensitivity, 47%, but a high specificity, 92%, for the detection of hyperparathyroid bone disease. The majority of patients had regional BMD values within the normal reference range and this test was of poor discriminatory value. The non-invasive markers were unable to distinguish between patients with low turnover, mild hyperparathyroidism and patients with normal histology. In conclusion the measurement of serum iPTH is a useful screening tool for the detection of hyperparathyroid bone disease which can be confirmed by the finding of a raised serum BAP or parathyroid enlargement. For definitive diagnosis, however, the gold standard remains bone biopsy and at present one cannot recommend any non-invasive method as an adequate substitute.

Adult↗
PubMed1995

Quality team approach in evaluating three automated hematology analyzers with five-part differential capability.

Three modern hematology analyzers (Abbott Cell-Dyn 3000, Coulter STKS, and Sysmex NE-8000) with high throughput and 5-part differential capability were evaluated using a protocol designed by a quality team. Effective use of the team process to evaluate instrumentation empowers laboratory personnel to share in decision-making activities, improves job satisfaction, and produces the best purchasing decision. Instruments were compared using a combination of statistical analysis and written evaluations provided by team members. Tools and concepts from this study provide a comprehensive model for an effective multi-instrument evaluation.

Automation↗