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J A Rees

Publications and source records attributed to J A Rees.

At least 19 recordsLinked to original sources
PubMed1999

Endothelial dysfunction in hypopituitary adults with growth hormone deficiency.

OBJECTIVES: Adult hypopituitarism with growth hormone deficiency (GHD) results in reduced exercise capacity, detrimental changes in body composition and lipid profiles and may be associated with an excess cardiovascular mortality. Endothelial dysfunction is an early event in the pathogenesis of atherosclerosis and predisposes to the deposition of unstable atherosclerotic plaques. We have used a noninvasive method to assess endothelial function in the brachial arteries of a group of treated hypopituitary adults with GHD, and a group of healthy age- and sex-matched controls. PATIENTS: Seventeen hypopituitary adults with GHD (13 male, 4 female) aged 26-54 years were studied. Each patient was receiving standard replacement therapy for all other hormonal deficiencies such that all target hormones were maintained in the normal reference range. All observations obtained were compared with those made in age- and sex-matched control subjects. All study subjects had no identifiable risk factors for endothelial dysfunction. MEASUREMENTS: Using an ultrasound vessel wall tracking system, the diameter of the left brachial artery was measured at rest, in response to reactive hyperaemia (endothelium-dependent dilation) and following sublingual glyceryl trinitrate (GTN) (endothelium-independent vasodilatation). We also measured fasting lipids, insulin, plasma glucose, glycated haemoglobin (HbA1c) and IGF-1, and studied the relationship of these parameters to endothelial function. RESULTS: Flow mediated endothelium-dependent dilatation (FMD), expressed as a percentage change from resting base-line diameter, was significantly impaired in the GHD group (3.70 +/- 2.36% vs. 7.30 +/- 2.42%, P < 0.001). In contrast, GTN-mediated dilatation was similar in both groups. There were no differences in total cholesterol, HDL cholesterol, LDL cholesterol or plasma triglyceride between the groups. Both fasting insulin (27.1 +/- 18.1 vs. 15.89 +/- 6.65 mU/l, P < 0.05) and glycated haemoglobin (HbA1c) levels (5.29 +/- 0.43 vs. 4.91 +/- 0.43%, P < 0.05) were significantly higher in the GHD group. FMD in both groups showed an inverse relationship with total cholesterol (r = -0.58, P < 0.05, GHD and r = -0.55, P < 0.05 controls). However, in the GHD subjects, there was a strong inverse relationship between FMD and LDL-cholesterol (r = -0.81, P < 0.0001). No other relationships were noted between FMD and any other metabolic parameters, or characteristics of GHD. CONCLUSIONS: Endothelial dysfunction is present in GH deficient adults prior to the onset of overt atherosclerotic disease. The similar glucose yet elevated fasting insulin levels imply a state of relative insulin insensitivity. The strong inverse correlation between endothelial dysfunction and LDL-cholesterol suggests a possible aetiological role for LDL-cholesterol in the pathogenesis of any excess cardiovascular risk associated with adult hypopituitarism.

Adult↗
PubMed1998

Cytochemical demonstration of sites of hydrogen peroxide generation and increased vascular permeability in isolated pig hearts after ischaemia and reperfusion.

Isolated pig hearts, subsequently perfused with pig or human blood, were prepared for the cytochemical demonstration of sites of hydrogen peroxide generation and increased vascular permeability. Oxidant stress was associated with ultrastructural changes commonly seen following myocardial reperfusion. In addition, the precipitation of cerium perhydroxide following perfusion with physiological saline containing cerium chloride suggested the vascular endothelium and leukocytes as sources of oxidants. This was associated with rapid penetration of horseradish peroxidase through the intercellular clefts of the vascular endothelium into the interstitial space, suggesting increased vascular leakiness at these sites. The rapid penetration of horseradish peroxidase was observed at all monitored periods of reperfusion with pig or human blood. This indicates that the increased permeability occurred during the ischaemic period and continued during reperfusion. Morphological damage was greatest in pig hearts reperfused with whole human blood and this was attenuated if the blood was preabsorbed to remove antibodies prior to reperfusion. We conclude that oxidant stress was initiated during ischaemia and continued during reperfusion in this model.

Animals↗
PubMed1997

Novel antibacterial peptides isolated from a European bumblebee, Bombus pascuorum (Hymenoptera, Apoidea).

We present here the isolation and characterization of four antimicrobial peptides produced by a European bumblebee Bombus pascuorum. A 51-residue insect defensin was characterized which, like the Apis mellifera defensins, had a highly conserved 12-residue extension to its C-terminal compared to defensins from other insects. Monoisotopic mass analysis of the C-terminal of B. pascuorum defensin confirmed that this molecule was C-terminally amidated. This defensin showed strong anti-Gram-positive activity and some anti-fungal activity; also, in contrast to other insect defensins, it showed anti-Gram-negative activity. A 17-residue apidaecin was characterized, showing anti-Gram-negative activity, and differing by a single amino acid substitution from the A. mellifera apidaecin. A 39-residue abaecin was isolated, the largest proline-rich antimicrobial peptide characterized to date, which showed activity against both Gram-negative and Gram-positive bacteria. Finally, we isolated an N-terminally blocked molecule, with a molecular mass of 10,122 Da, which showed activity against Gram-negative bacteria only. These characteristics are reminiscent of hymenoptaecin from the honeybee A. mellifera, but a definitive characterization of this molecule awaits further work. No evidence of lysozyme activity was found in the haemolymph of challenged or naive B. pascuorum.

Amino Acid Sequence↗
PubMed1997

Splenomegaly.

Explore the source record for details and available documents.

Foot↗
PubMed1994

Lack of peroxisome proliferation in marmoset liver following treatment with ciprofibrate for 3 years.

The effect of treatment of marmosets with ciprofibrate for 3 years on activities of hepatic enzymes, hepatic histomorphology, and ultrastructure were investigated. Male and female marmosets were dosed with ciprofibrate (2, 10, and 20 mg/kg) by oral gavage once daily for 3 years. No effect on liver weight (adjusted for body weight) or liver morphology was observed. The activities of catalase, glutathione peroxidase, alpha-glycerophosphate dehydrogenase, benzphetamine N-demethylase, and ethoxyresorufin O-deethylase were unaffected by treatment with ciprofibrate. Activity of glutathione transferase was increased in the low dosage group but unaffected in the mid and high dosage groups. Modest increases in activities of peroxisomal beta-oxidation (2.5-fold, maximal), carnitine acetyl transferase (1.7-fold, maximal), and carnitine palmitoyl transferase (2-fold, maximal) were observed. Cytochemical staining and quantitative image analysis failed to indicate any effect on peroxisomal number, size, or volume density. Similarly, there was no increase in lipofuscin deposition. This study provides data on the effects of a potent peroxisome proliferator on primate liver following a dosing period much greater than that used in previously published studies and is further evidence that the marmoset is relatively insensitive to the well-documented effects that ciprofibrate and other peroxisome proliferators have on rat liver.

Animals↗
PubMed1993

Management of hyperlipidaemia: guidelines of the British Hyperlipidaemia Association.

There is considerable evidence to suggest that the identification and treatment of dyslipidaemia will reduce the risk of premature CHD, i.e. before the age of 65. Diagnosis of the cause of raised plasma lipid levels will enable appropriate decisions to be taken with regard to management. The cornerstone of treatment is nutritional counselling and attention to other major risk factors for CHD, particularly smoking and hypertension. For a small percentage of patients with severe hyperlipidaemia drug therapy is indicated. Appropriate drug choices need to be made based on the particular lipid abnormality to be treated. In general those patients with clinical vascular disease are treated more aggressively than those where the aim is primary prevention. More research is needed to determine individual risk more precisely and to allow proper targeting of therapy. Genetic factors, qualitative changes in lipoproteins, lipoprotein (a), fibrinogen, and other coagulation and thrombotic factors are likely to be important in individual risk assessment. There is no doubt that more information is needed from prospective studies of lipid-lowering therapy in terms of risk benefit for affected individuals. Hopefully the major studies currently underway will fill some of the gaps in our knowledge. Until then aggressive therapy with drugs should be reserved for those at highest risk where the benefit is likely to be greatest.

Cholesterol, Dietary↗
PubMed1990

Microvascular invasion of rabbit growth plate cartilage and the influence of dexamethasone.

The normal morphological features of growth plate angiogenesis were examined in rabbits and compared with changes induced by dexamethasone. Penetration of growth plate cartilage was led by perivascular cells with some contribution by luminal capillary endothelial cells. There was a close relationship between the invasive perivascular cells and the luminal endothelial cells of the capillary tip. Growth plates from rabbits treated with dexamethasone underwent major changes in the pattern of capillary invasion. Most striking was the appearance of numerous narrow and tortuous channels which penetrated the cartilage, in some cases forming complete loops. These channels were filled with debris or red cells but did not contain capillaries. It is suggested that dexamethasone treatment leads to channel formation by disrupting the normal control of capillary invasion.

Animals↗
PubMed1988

Ultrastructural localisation of alkaline phosphatase activity in osteoarthritic human articular cartilage.

The distribution of alkaline phosphatase activity in human articular cartilage from normal and osteoarthritic joints has been examined by an electron microscope technique, probably for the first time. In osteoarthritic cartilage chondrocytes and matrix vesicles close to the tidemark were positive for alkaline phosphatase activity. Large numbers of matrix vesicles were found within the extracellular matrix of osteoarthritic cartilage, and there is a specific relation between phosphatase activity, matrix vesicles, and initial mineral formation in the tidemark region of articular cartilage.

Aged↗
PubMed1987

The prescribing of chloroquine and hydroxychloroquine by consultant rheumatologists in the UK.

A questionnaire on chloroquine and hydroxychloroquine prescribing was circulated nationally to 212 consultant rheumatologists and 119 replies were analysed. Of all patients receiving second-line drugs, 10% were prescribed antimalarials, with hydroxychloroquine being used four times more frequently than chloroquine. Eighty-five per cent of rheumatologists always used the same dose of hydroxychloroquine or chloroquine. Only 5% considered patient's weight in deciding the dose. Fear of ocular toxicity was expressed by many physicians; 54% had experienced corneal deposits; 4% retinopathy and 40% believed cumulative dose determined toxicity. Much confusion existed over the necessity for and frequency of ophthalmological monitoring. Only 56% requested ophthalmological tests before commencing treatment, although 86% monitored the eyes during therapy. Other side-effects were believed to affect 1-10% of patients, with no anticipated difference between doses of 250 mg chloroquine and 400 mg hydroxychloroquine daily.

Arthritis, Rheumatoid↗
PubMed1987

Ultrastructural localisation of fibronectin in human osteoarthritic articular cartilage.

A protein A-gold immunolocalisation technique has been used on sections of femoral head articular cartilage to localise fibronectin. Chondroitinase treatment enhanced gold staining, particularly when tissue samples were digested before fixation. The greatest accumulations of fibronectin were seen in the surface zone of osteoarthritic cartilage. Disease free cartilage contained very little fibronectin in this region. Cells which appeared to produce fibronectin were rare in normal specimens but common in the superficial region of osteoarthritic cartilage. These chrondrocytes appeared to release fibronectin as part of an amorphous material which accumulated in the pericellular region. This is the first ultrastructural demonstration of fibronectin synthesis by articular cartilage chondrocytes.

Adult↗
PubMed1987

Reduced life span of the osteoclast in osteopetrotic (mi and midi) mice.

Osteoclasts were enumerated on the parietal bones of mice carrying combinations of alleles (mi, midi and +) at the microphthalmic locus. Homozygous mutants at this locus show varying degrees of osteopetrosis due to defective bone resorption. As the severity of the bone resorption defect increased across the genotypes, there was an increase in the total number of osteoclasts and also an increase in the proportion of uninucleate osteoclasts. In parietal bones incubated for 24 h with parathyroid hormone (PTH) there was no significant difference between osteopetrotic and normal bones in terms of the number of osteoclast nuclei that had taken part in fusion. When bones were incubated for 24 h in the absence of PTH the percentage of osteoclasts remaining was correlated inversely with the severity of the bone resorption defect. Thus, we suggest that the increased proportion of uninucleate osteoclasts in these mutants results from a shortened life span, reducing the time-dependent accumulation of nuclei. This implies a reduced efficiency of uninucleate osteoclasts over multinucleate ones and we speculate on the reason for this.

Alleles↗
PubMed1986

Distribution of alkaline phosphatase activity in experimentally produced callus in rats.

Experimentally produced fractures in long bones studied by light and electron microscopic histochemistry were found to heal by a process of enchondral calcification. There was intense proliferation in the cells of the cambium layer of the periosteum, with differentiation to chondroblasts and osteoblasts, suggesting that this layer was the primary tissue responsible for development of the callus. Cytoplasmic processes of the hypertrophic chondrocytes appeared to bud and produce matrix vesicles. Alkaline phosphatase activity was detected along the plasma membrane of the hypertrophic chondrocytes and around the matrix vesicles, before any signs of mineral deposition. Calcification took place by deposition of hydroxyapatite crystals in and around these matrix vesicles which frequently showed alkaline phosphatase activity. It is suggested that there is a close functional association between alkaline phosphatase activity and calcification in the process of fracture healing, which is another type of enchondral calcification mediated by matrix vesicles.

Alkaline Phosphatase↗
PubMed1984

Comparison of prescription costs within a group practice.

Records of prescriptions that originated from one group practice and were dispensed at one pharmacy were maintained for one year. The information recorded included the age and sex of the patients, the name of the prescribing doctor, and the drug(s) prescribed and their cost. Analysis of the records showed considerable differences in average prescription costs among doctors. For all the major therapeutic groups, repeat prescriptions were more expensive than new prescriptions, children had cheaper prescription costs than adults, and prescriptions for women were cheaper than those for men. Within an age-sex group or a therapeutic group, however, prescription costs were similar for each doctor. These results indicate that the differences in overall prescribing costs among doctors were not due to different management of the same disorders, but were due to different types of patients being seen.

Adolescent↗