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Biomedical subjects

C S Cockram

Publications and source records attributed to C S Cockram.

At least 199 records · Page 11Linked to original sources
PubMed1990

Structure-function relationships of insulin receptor interactions in cultured mouse astrocytes.

Insulin receptor binding and effects upon uridine incorporation into nucleic acid were studied and compared to 3 insulin analogues, DPI, DPI-amide and DOI, in primary cultures of mouse astrocytes. From half-maximal inhibition of [125I]monoiodoinsulin binding (0.14 nM), the relative binding affinities of DPI, DPI-amide and DOI were 20%, 80% and 4% as compared with the native insulin, respectively. IC50 values were 158.5 nM for insulin, 199.5 nM for DPI-amide, 794.3 nM for DPI and 3980 nM for DOI. The corresponding relative potencies in stimulating [14C]uridine incorporation into TCA-insoluble material were 9% for DPI, 100% for DPI-amide and 1.1% for DOI. These findings are commensurate with data for these analogues in other insulin-sensitive tissues. It is concluded that the astrocyte insulin receptor has similar structural requirements to receptor in tissues outside the CNS, at least in terms of the involvement of the C-terminus of the insulin B-chain.

Animals↗
PubMed1990

Erythrocyte sodium fluxes, ouabain binding sites, and Na+,K(+)-ATPase activity in hyperthyroidism.

Erythrocyte sodium pump activity, in contrast to other tissues, is decreased in hyperthyroidism. In order to examine whether the effect of thyroid hormones on erythrocytes is part of a generalized effect on other transport pathways, we measured sodium pump activity, Na+,K(+)-adenosine triphosphatase (ATPase) activity, ouabain binding sites, bumetanide-sensitive sodium potassium cotransport (SPC), sodium lithium countertransport (SLC), and ouabain- and bumetanide-insensitive passive efflux of sodium (sodium "leak") in erythrocytes from 20 healthy subjects and 18 untreated hyperthyroid subjects. Sodium pump activity (ouabain-sensitive sodium efflux rate constant), Na+,K(+)-ATPase activity, and the number of ouabain binding sites were lower and the erythrocyte sodium content was higher in hyperthyroid subjects. The rate constants of erythrocyte SPC (P less than .05), SLC (P less than .001), and sodium "leak" (P less than .05) were also significantly lower in hyperthyroidism. In 11 of the hyperthyroid subjects, sodium flux measurements were repeated after 20 weeks of treatment. Sodium pump activity, the number of ouabain binding sites, and the rate constant for SLC increased. These results suggest that the effect of thyroid hormones on the erythrocyte sodium pump is part of a generalized effect on membrane proteins, rather than a specific effect.

Adult↗
PubMed1990

A comparison of fructosamine and glycosylated haemoglobin measurements at a diabetic clinic.

Fructosamine or glycosylated haemoglobin (HbA1) measurements are most useful in the diabetic clinic if results are available when the patient is seen, with minimum waiting time. Fructosamine measurements have the advantage of being cheaper and faster to perform on large numbers of patients than HbA1 measurements. In order to assess the acceptability of fructosamine as a complete alternative to HbA1, fructosamine, HbA1 and random plasma glucose measurements were made on all patients attending the diabetic clinic for a 6-week period. Either the fructosamine or the HbA1 result was made available when the patient was seen and the other result was given at the end of the clinic for comment as to whether or not it would have altered management. The clinicians indicated that in 7% of cases, the HbA1 result would have altered management if available when the patient was seen, whereas in 2.5% of cases, the fructosamine result would have altered management. The commonest discrepancy was disproportionate elevation of HbA1 with a normal or near normal fructosamine. For the whole group, 32% had a normal fructosamine but only 16% a normal HbA1. The best overall correlation was between HbA1 and glucose (r = 0.67). Fructosamine correlated less well with both HbA1 (r = 0.55) and glucose (r = 0.51). Thus fructosamine was an acceptable alternative to HbA1 in most cases but caution is required, particularly in patients with persistently normal fructosamine results for whom additional HbA1 checks are advised.

Biomarkers↗
PubMed1990

Septicaemia in Hong Kong.

In a five-year prospective study of blood culture-positive septicaemia in a Hong Kong teaching hospital there were 2211 clinically-significant episodes, of which 16% occurred in children less than 15 years old. The microbiology and clinical features were broadly similar to those seen in Europe and North America, but with some important differences. Two-thirds of episodes were community-acquired. The most common organism isolated from community-acquired septicaemias was Escherichia coli and the source, most commonly, the urinary tract. However, the biliary tract was the second most common source of community-acquired infection (25%), reflecting the frequency of liver disease in Hong Kong. Three per cent of community-acquired septicaemias were associated with endocarditis; half of these were with viridans streptococci, usually in patients with rheumatic heart disease, and 40% were in drug addicts with methicillin-sensitive Staphylococcus aureus. The commonest organisms causing community-acquired childhood infections were Salmonella spp. (27%) and Streptococcus pneumoniae (22%), whereas pneumococci accounted for only 3% of adult community-acquired micro-organisms. Haemophilus influenzae infections were uncommon and there was no case of meningococcal or gonococcal septicaemia. The commonest cause of hospital-acquired septicaemia was Staph. aureus (24%), of which 46% were methicillin-resistant. The characteristics of septicaemia in Hong Kong are influenced by the patient population structure, endemic disease patterns, local medical practice and socio-economic factors, but the rarity of Str. pneumoniae in adults and of H. influenzae and Neisseria meningitidis in children is unexplained.

Adolescent↗
PubMed1990

Incidence, causes and mechanism of hypercalcaemia in a hospital population in Hong Kong.

To determine the incidence and causes of hypercalcaemia in a hospital population in Hong Kong, all 29,107 samples received in the laboratory in one year were analysed for plasma calcium and albumin, and samples with a plasma calcium concentration adjusted for albumin greater than 2.55 mmol/l were investigated. Plasma calcium greater than 2.55 mmol/l was found in 462 patients. Repeat samples were received from 302 of these and hypercalcaemia was confirmed in 183. The main causes of hypercalcaemia were malignancy (72.1 per cent), tuberculosis (6.0 per cent), and primary hyperparathyroidism (5.5 per cent). In the malignant hypercalcaemia group, carcinoma of lung was the most common (31.8 per cent) and carcinoma of breast was uncommon (3.0 per cent). Secondary deposits in bone were detected in 35 of the 122 solid tumours. In order to identify the mechanism of hypercalcaemia the contributions of renal tubular reabsorption and increased bone resorption to the plasma calcium concentration were calculated. Increased tubular reabsorption was the main contributor to hypercalcaemia in primary hyperparathyroidism and carcinoma of liver (none of whom had bony metastases) and it contributed significantly to hypercalcaemia in carcinoma of lung without bony metastases and carcinoma of oesophagus. We conclude that in Hong Kong (a) primary hyperparathyroidism is uncommon, (b) tuberculosis is an important cause and (c) humoral factors may be responsible for a relatively high proportion of cases of malignant hypercalcaemia.

Aged↗
PubMed1990

Serum soluble interleukin 2 receptor in hyperthyroid Graves' disease and effect of carbimazole therapy.

To study the activation of T lymphocytes in hyperthyroid Graves' disease, the serum concentrations of soluble interleukin 2 receptors (sIL2R) were determined during active thyrotoxicosis and following the return to a euthyroid state with carbimazole therapy. Serum sIL2R was measured by an enzyme linked immunoassay. The mean +/- SD serum sIL2R concentration during untreated hyperthyroidism was elevated as compared with controls (919.1 +/- 523.4 vs 374.2 +/- 189.4 U/ml, P less than 0.005). However, after carbimazole therapy the serum sIL2R in euthyroid patients fell to 377.9 +/- 90.3 U/ml, which did not differ from healthy controls. Serum sIL2R correlated significantly with the serum free T3 only during hyperthyroidism (r = 0.678, P less than 0.01). Our study suggests that in vivo measurement of serum sIL2R released from activated T lymphocytes is a useful immunological indicator of disease activity.

Adult↗
PubMed1990

The effect of hyperthyroidism on in vivo aging of erythrocyte ouabain-binding sites and intracellular sodium and potassium.

The sodium pump activity of erythrocytes is inhibited in hyperthyroidism, whereas in all other cells it is increased. To examine the possibility that thyroid hormones cause an accelerated loss of membrane proteins during in vivo aging, we determined the number of ouabain-binding sites (OBS) in young and old erythrocytes from 13 hyperthyroid and 13 euthyroid subjects. Erythrocytes were separated according to their cell age by centrifugation. In euthyroid subjects, the median number of OBS decreased from 415 (range, 341-551; mean +/- SEM, 440 +/- 19.1) in young cells to 336 (range, 287-453; mean, 340 +/- 13.6) in old cells. In hyperthyroid subjects the median number of OBS decreased from 290 (range, 190-370; mean, 280 +/- 13.3) in young cells to 207 (range, 155-244; mean, 208 +/- 7.5) in old cells. In hyperthyroid subjects the number of OBS of erythrocytes of all ages was lower than that in euthyroid subjects. The ratio of OBS between young and old cells in hyperthyroid subjects (median, 1.27; mean +/- SD, 1.34 +/- 0.16) was similar to that in euthyroid subjects (median, 1.29; mean, 1.30 +/- 0.12). We conclude that these results do not support the hypothesis that in hyperthyroidism there is accelerated loss of sodium pump sites during the lifespan of erythrocytes in circulation.

Adult↗
PubMed1990

Urinary excretion of albumin and enzymes in non-insulin-dependent Chinese diabetics.

Urine albumin (Alb), total protein (TP) and creatinine (Cr) concentrations and the activities of N-acetyl-beta-D-glucosaminidase (NAG), alanine aminopeptidase (AAP) and gamma-glutamyl transpeptidase (GGT) were measured in untimed random urine samples from 157 non-insulin-dependent (NIDDM) diabetic subjects and 54 healthy subjects. In NIDDM subjects the excretions of TP, Alb, NAG, AAP, GGT (expressed in relation to creatinine) were significantly higher and were abnormal in 59.9%, 68.8%, 47.2%, 41.4% and 13.4% of the subjects, respectively. However, 24.5%, 22.4% and 6.1% of NIDDM subjects with normal Alb/Cr ratio had abnormal excretion of NAG, AAP and GGT, respectively. Alb/Cr ratio was greater than 26.8 mg/mmol (considered to be equivalent to albumin excretion of 250 mg/24 h) in 14.6% and between 2.5-26.8 mg/mmol (equivalent to albumin excretion rates of 20-250 mg/24 h) in 54.1% of subjects. In those diabetic subjects with clinical retinopathy only Alb/Cr ratio was higher. Arterial blood pressure was significantly correlated with Alb/Cr (r = 0.365) and NAG/Cr (r = 0.204). We conclude that prevalence of abnormal Alb/Cr is relatively common among Chinese NIDDM subjects.

Acetylglucosaminidase↗
PubMed1990

Response to control of hyperthyroidism in patients with myasthenia gravis and thyrotoxicosis.

Three patients presenting with both myasthenia gravis and thyrotoxicosis were treated initially with pyridostigmine and carbimazole respectively. Control of the hyperthyroidism was achieved in all cases but was accompanied by deterioration of the myasthenic symptoms in two and persistence in one. Thymectomy was performed with subsequent improvement in all three patients. Histology showed thymic hyperplasia in each case. The relationship of myasthenia gravis, thyrotoxicosis and the thymus is discussed.

Adult↗
PubMed1990

Bites by the white-lipped pit viper (Trimeresurus albolabris) and other species in Hong Kong. A survey of 4 years' experience at the Prince of Wales Hospital.

The case records of 242 snake bite victims admitted to the Prince of Wales Hospital in Hong Kong between September 1984 and October 1988 were studied retrospectively. When the snake was identified, the White-lipped pit viper (Trimeresurus albolabris) was by far the commonest species involved. In addition to local oedema and inflammation, evidence of a significant blood clotting disturbance was present in at least 10% of cases, defibrination and thrombocytopenia being the commonest findings. Since such abnormality was not always sought the true figure is likely to be higher. Three fatalities occurred, one of which was secondary to a probable White-lipped pit viper bite, one to a bite by Chinese cobra and one to a bite by Russell's viper.

Adult↗
PubMed1990

Handling of blood specimens for glucose analysis.

There is no consensus concentration of sodium fluoride (NaF) required for preserving glucose in blood specimens. We examined the effectiveness of different concentrations of NaF. Glucose concentration in blood samples decreased with time, despite the presence of a high concentration of NaF (12 g/l). The decrease in glucose concentration was less with increasing amounts of NaF but could not be totally abolished. The clinical implications of these pre-analytical errors is discussed.

Adult↗
PubMed1989

Functional substance P receptors on a human astrocytoma cell line (U-373 MG).

[125I]Bolton Hunter conjugate of substance P ([125I]BHSP) can bind to human astrocytoma membranes in a monophasic and saturable manner with a Kd of 0.57 +/- 0.17 nM and a Bmax of 67.8 +/- 5.5 fmol/mg protein. The rank order of potency of tachykinins and related analogues as inhibitors of [125I]BHSP binding to astrocytoma membranes and intact cells correlated with their relative abilities to stimulate uridine incorporation into nucleic acid. The observed specificity pattern conformed to that reported for the NK1 tachykinin receptor with SP much greater than eledoisin greater than neurokinin A greater than neurokinin B and [Glp6, L-Pro9]SP(6-11) much greater than [Glp6, D-Pro9]SP(6-11).

Astrocytoma↗
PubMed1989

Mouse astrocytes possess specific ANP receptors which are linked to cGMP production.

1. Receptors for atrial natriuretic peptide (ANP) have been identified on mouse astrocytes in primary culture, and have similar characteristics to those found on previously recognized ANP-target tissues. 2. Scatchard analysis revealed one class of high affinity receptors with a Kd of 0.32 nmol/L. The IC50 for specific binding was 0.5 nmol/L. 3. Ligand binding resulted in stimulation of guanylate cyclase. 4. Under reducing conditions, the covalently cross-linked receptor-ANP complex migrated on SDS-polyacrylamide gels as a single band with an apparent molecular weight of 66 kDa. 5. Although the physiological relevance of our observations remains to be determined, these data document that cultured mouse astrocytes contain specific high-affinity ANP receptors which are linked to the production of cGMP.

Animals↗
PubMed1989

Insulin binding to human astrocytoma cells and its effect on uridine incorporation into nucleic acid.

Binding of [125I]monoiodoinsulin to human astrocytoma cells (U-373 MG) was time dependent, reaching equilibrium after 1 h at 22 degrees C with equilibrium binding corresponding to 2.2 fmol/mg protein: this represents approximately 2,000 occupied binding sites per cell. The t1/2 of 125I-insulin dissociation at 22 degrees C was 10 min; the dissociation rate constant of 1.1 X 10(-2) s-1 was unaffected by a high concentration of unlabeled insulin (16.7 microM). Porcine insulin competed for specific 125I-insulin binding in a dose-dependent manner and Scatchard analysis suggested multiple affinity binding sites (higher affinity Ka = 4.4 X 10(8) M-1 and lower affinity Ka = 7.4 X 10(6) M-1). Glucagon and somatostatin did not compete for specific insulin binding. Incubation of cells with insulin (0.5 microM) for 2 h at 37 degrees C increased [2-14C]uridine incorporation into nucleic acid by 62 +/- 2% (n = 3) above basal. Cyclic AMP, in the absence of insulin, also stimulated nucleoside incorporation into nucleic acid [65 +/- 1% (n = 3)] above basal. Preincubation with cyclic AMP followed by insulin had an additive effect on nucleoside incorporation [160 +/- 4% (n = 3) above basal]. Dipyridamole (50 microM), a nucleoside transport inhibitor, blocked both basal and stimulated uridine incorporation. These studies confirm that human astrocytoma cells possess specific insulin receptors with a demonstrable effect of ligand binding on uridine incorporation into nucleic acid.

Astrocytoma↗