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Biomedical subjects

J J Taljaard

Publications and source records attributed to J J Taljaard.

At least 127 records · Page 7Linked to original sources

Neonatal pancreatic function in infants born to mothers with gestational and overt diabetes.

Neonatal pancreatic function was assessed in infants born to non-diabetic mothers and to mothers with well-controlled gestational diabetes (GD) and overt diabetes (OD) using cord blood C-peptide estimations and the calculation of cord C-peptide/glucose ratios. Exaggerated pancreatic function was present in infants born to mothers with GD. In these infants the increased cord C-peptide values and cord C-peptide/glucose ratios correlated with their increased birth weight ratios. These results could not be explained on the basis of maternal hyperglycaemia and a possible intrinsic difference in pancreatic response between infants born to mothers with GD and those born to mothers with OD is suggested.

Blood Glucose↗

Methylprednisolone and the adult respiratory distress syndrome.

Total hip replacement was carried out on 22 patients under general anaesthesia. Of these, 10 were pretreated with methylprednisolone (30 mg/kg); 1 of these developed the adult respiratory distress syndrome (ARDS) and had high levels of thromboxane B2 (TXB2) 5 minutes after fixation of the femoral prosthesis and at the end of the operation. The other 12 patients served as controls; 5 of them developed ARDS and had statistically significant higher TXB2 levels than the other 7 control patients who remained well. All patients who did not develop ARDS had low TXB2 levels. TXB2 and beta-thromboglobulin levels followed the same trend and there was good correlation (r=0,6806; P less than 0,01) at the end of the operation in the control group patients who developed ARDS. There was no statistical difference in 6-keto-PGF1 alpha levels between the patients who developed ARDS and those in the control group who remained well. Steroids reduce arachidonic acid metabolism by inhibiting the release of substrate for cyclo-oxygenase and lipoxygenase activity. Patients prone to ARDS thus benefit from methylprednisolone administration.

Aged↗

The effect of ventilatory patterns on prostacyclin (PGI2) synthesis in the lung.

Prostacyclin (PGI2) appears to be synthesized in the lungs of man and experimental animals. It has been stated that PGI2 must be regarded as a local hormone that inhibits platelet adhesion to vessel walls only very close to the site of synthesis. The wide range of normal values given for PGI2 may be related to the sensitivity and exclusiveness of the different assay techniques used. In animals hyperventilation increases PGI2 synthesis by the lung, but in agreement with other authors we demonstrated that hyperventilation did not influence PGI2 synthesis in man. We used a radio-immunoassay technique to estimate PGI2 levels.

Aged↗

Possible modulation of phosphorylation of acetylcholine receptor-enriched membrane preparations.

During phosphorylation of acetylcholine receptor (AChR)-enriched membrane preparations from Torpedo fuscomaculata , phosphate is incorporated into a single protein, with a molecular weight corresponding to that of one of the receptor subunits (37,000 daltons). This protein also seems to contain the receptor binding site. ATP binds to four protein species, one of which corresponds to a different subunit of the receptor (molecular weight 45,000). Phosphorylation of these membrane preparations is affected by several factors, known to be involved in postsynaptic events. Ca2+ (10 microM) inhibits the reaction, whereas cGMP (20 microM), causes stimulation. Furthermore it has been shown that the agonists, acetylcholine, and carbamylcholine (10 microM and 1 microM) stimulate the phosphorylation reaction, while the antagonists, tubocurarine, hexamethonium, and decamethonium (1 microM), cause inhibition.

Acetylcholine↗

Alpha 2 and beta-adrenoceptor agonists modulate [3H]dopamine release from rat nucleus accumbens slices: implications for research into depression.

The modulatory effects of noradrenergic agonists on the 25 mM K+-induced release of [3H]dopamine (3H-DA) from rat brain nucleus accumbens slices was investigated, using a superfusion technique. The K+-induced release of 3H-DA was Ca2+ dependent, significantly enhanced (25-32%; p less than 0.02) by the beta-adrenoceptor agonist isoproterenol (10 microM), and significantly decreased (13-25%; p less than 0.05) by the alpha 2-adrenoceptor agonist clonidine (10 microM). At these concentrations neither drug affected basal release of 3H-DA. Clonidine (100 microM) increased the basal release of 3H-DA, while decreasing the K+-induced release by 19% (p less than 0.01). The inclusion of desipramine in the incubation medium, to prevent accumulation of 3H-DA into noradrenergic neurons, did not alter the inhibitory effect of clonidine (10 microM) on 3H-DA release. This study provides direct evidence that noradrenergic neurons can modulate dopaminergic neurotransmission in the mesolimbic system.

Animals↗

Ontogeny of estradiol-2-hydroxylase activity in discrete brain areas of Wistar rats.

Estradiol-2-hydroxylase activity was assayed radio-enzymatically in microsomes of six different brain areas of male and female Wistar rats between 22 and 77 days of age. The hypothalamus consistently showed the lowest activity and the hippocampus the highest, with the other areas falling in between. This pattern was seen in both sexes and at all the ages studied. In both sexes all six brain areas showed a steady increase in activity with increasing age. No statistically significant sexual differences in activity were observed for any area. The relatively low estradiol-2-hydroxylase activity in the hypothalamus is noteworthy since it contradicts the published evidence that this area has the highest in vitro catecholestrogen forming capacity in the brain.

Aging↗

Adenosine deaminase levels in cerebrospinal fluid in the diagnosis of tuberculous meningitis.

The prognosis of tuberculous meningitis is closely linked to the stage at which treatment is started. At the same time the diagnosis will often have to be made on purely circumstantial evidence. Adenosine deaminase activity in the cerebrospinal fluid was evaluated as a diagnostic aid in 30 cases of tuberculous meningitis. Cerebrospinal fluid adenosine deaminase levels differentiated tuberculous meningitis cases from those with aseptic meningitis being higher than 4 U/l in all and higher than 6 U/l in 90% of cases of tuberculous meningitis, but lower than 6 U/l in aseptic meningitis and less than 4 U/l in normal controls. It could not distinguish bacterial meningitis from tuberculous or aseptic meningitis. In cases of low-cell-count bacterial meningitis, the mean cerebrospinal fluid adenosine deaminase level was significantly lower than in cases of tuberculous meningitis with a similar cell count, but considerable overlap of results in the two groups was still to be found.

Adenosine Deaminase↗

The effect of acute haemodilution during cardiopulmonary bypass on blood calcium, pH, phosphorus and protein values.

The changes in total serum calcium, ionized calcium, total serum protein, albumin and phosphate levels during cardiopulmonary bypass were measured. The possible causes of the changes in these parameters are discussed. The effect of the presence of heparin on serum ionized calcium is evaluated. The metabolic and clinical significance of the changes in blood components measured are discussed, special attention being paid to the use of calcium as an inotropic agent at the termination of cardiopulmonary bypass.

Blood Proteins↗

Phosphorylation increases alpha-bungarotoxin binding to acetylcholine receptor-enriched membrane preparations.

Acetylcholine receptor (AChR)-enriched membrane preparations from Torpedo electroplax bind alpha-bungarotoxin with a KD of 8.4 nM and the concentration of binding sites is 16 pmoles/mg protein. When, however, the alpha-toxin is incubated with receptor samples, phosphorylated in the presence of Mn2+ (10 mM) and ATP (0.5 mM), the concentration of binding sites is increased to 94 pmoles/mg protein, although there is no marked change in the KD (11 nM). Binding of acetylcholine to AChR-enriched membrane preparations occurs at a receptor which has two different conformational states with KD's of 8.4 nM and 520 nM. The concentration of binding sites for the high affinity component is 1.35 pmoles/mg protein and for the low affinity component is 12 pmoles/mg protein. The effect of phosphorylation of the AChR on agonist binding could not be determined.

Acetylcholinesterase↗

Inhibition of Na+, K+-ATPase activity by delta-aminolevulinic acid.

delta-Aminolaevulinic acid (ALA) has been shown to be toxic to cultured neurons and glia at concentrations as low as 10 microM. In an attempt to elucidate the mechanism of toxicity, the effects of ALA on membrane ATPase activity were investigated. Exposure of neuron cultures to 1 mM ALA for 7 days caused a substantial decrease in both Na+, K+-ATPase and Mg2+-ATPase activities. At lower concentrations, ALA affected only the Na+, K+-component. ALA appeared to act directly, inhibiting Na+, K+-ATPase activity in rat brain cortex membrane preparations at 10 microM. Although this effect was slight, it may well represent the mechanism of action of ALA, since ouabain, a potent inhibitor of Na+, K+-ATPase activity, proved to be more toxic to cultured neurons than ALA. Furthermore, cardiac glycoside overdosage causes neurological disturbances which are very similar to those observed in the acute attack of porphyria.

Adenosine Triphosphatases↗

Ontogeny and sexual dimorphism of estradiol-2-hydroxylase activity in rat liver microsomes.

A radio-enzymatic method was used to measure the activity of estradiol-2-hydroxylase in liver microsomes of male and female Wistar rats, ranging in age from 10 to 63 days. In pre-pubertal rats (10-30 days) the Vmax increased, but revealed no sex differences. After 30 days of age, however, it decreased in females. In males, on the other hand, it increased still further, reaching a maximum in adulthood. The apparent Km showed no significant sex differences in pre-pubertal rats, but appeared to decline after puberty in females. In females puberty was also associated with the appearance of important changes in the kinetic properties of estradiol-2-hydroxylase. These changes were reflected in hyperbolic Lineweaver-Burk plots. Hill plots of this data gave straight lines with slopes significantly less than one--indicating negative cooperativity. Alternatively the hyperbolic Lineweaver-Burk plots could mean that the enzyme consists of more than one form, which act on the same substrate, but with different affinities. It is concluded that development in female Wistar rats is associated with important qualitative changes in the kinetic properties of estradiol-2-hydroxylase and that factors which become operative during puberty play a key role in initiating these changes.

Aging↗

A possible role for phosphorylation of the acetylcholine receptor.

The acetylcholine receptor (AChR) from Torpedo fuscomaculata can be phosphorylated. This reaction was fully characterised. In addition, the influence of factors with possible modulatory effects on the phosphorylation of this receptor were investigated. In order to suggest the possible role of phosphorylation in neurotransmission, the effects of this reaction on the binding of ligands to the AChR were investigated. It was found that phosphorylation enhanced the binding of the antagonist, alpha-bungarotoxin to the AChR. Due to experimental difficulties the effect on binding of the agonist, acetylcholine, to the receptor, could not be determined. However, a hypothesis is proposed regarding the role of phosphorylation of the AChR in neurotransmission.

Acetylcholine↗

Early recognition of pulmonary dysfunction during intramedullary orthopaedic surgery.

Peri-operative partial arterial oxygen tension (PaO2) was monitored in 20 patients undergoing total hip replacement. Three distinct groups emerged on analysis of the arterial oxygen tensions. In group I there was no initial decrease in PaO2 but it rose above baseline level towards the end of the procedure. In group II there was a distinct fall in PaO2 during the acetabular and femoral stages of the operation. On termination of the procedure PaO2 had returned to baseline levels. In group III PaO2 values were significantly lower than those in group II during the acetabular and femoral stage s and decreased further at the end of the procedure. One patient in group II and 6 in group III developed postoperative pulmonary dysfunction. A progressive deterioration in PaO2 during hip replacement without recovery at end of the procedure indicates that the patient is likely to develop postoperative pulmonary dysfunction.

Aged↗

Characterization of protein phosphorylation in acetylcholine receptor-enriched membrane preparations from Torpedo fuscomaculata.

When the acetylcholine receptor (AChR) from Torpedo is phosphorylated, ATP is found to bind non-covalently to the preparation. After correction is made for this binding of ATP, the phosphorylation reaction has a Km of 0,16 mM, a pH optimum of 8,6 and reaches maximal activity within 3 min. The intrinsic kinase activity is very specific for the AChR and does not phosphorylate either histones or phosvitin. The only amino acid to be phosphorylated is serine and cyclic GMP causes stimulation of the reaction.

Acetylcholine↗

Effects of delta-aminolaevulinic acid, porphobilinogen and structurally related amino acids on 2-deoxy-glucose uptake in cultured neurons.

The effects of delta-aminolaevulinic acid (ALA), porphobilinogen (PBG), gamma amino-butyric acid (GABA), muscimol, glutamic acid and kainic acid on [3H]2-deoxy-D-glucose uptake by cultured neurons were investigated. Exposure to the cultures for 4 days, to ALA at concentrations as low as 10 microM caused a significant, dose-dependent decrease in [3H] 2-deoxy-D-glucose uptake. Neither ALA nor PBG appeared to interfere directly with glucose transport into the neuron but 1 mM ALA caused an initial stimulation of [3H] 2-deoxy-D-glucose uptake which increased to a maximum after 4 hr and fell to below control values after 19 hr exposure. GABA and muscimol caused similar increases in [3H] 2-deoxy-D-glucose uptake but these values remained above control levels after 19 hr exposure. Glutamic acid and kainic acid caused an immediate increase in [3H] 2-deoxy-D-glucose uptake which declined to minimum values after 4 hr exposure. The effect of ALA on glucose utilization in neurons may be of particular relevance to patients with acute porphyria where a genetic lesion in neural haem and haemoprotein biosynthesis is postulated to occur. ALA appeared to be more toxic to the neurons than any of the other compounds tested, possibly causing a critical depletion of energy reserves and cell death.

Aminolevulinic Acid↗

Cyclic AMP independent protein kinase activity in rat cerebral cortex synaptic vesicles--partial characterization.

The intrinsic protein kinase activity of a highly purified synaptic vesicle preparation was characterized. The time-course of the reaction was found to be rapid and linear for about 1 min, but plateaued after 30 min by which time approximately 1 nmol of 32P per mg protein was incorporated into trichloroacetic acid precipitated vesicular protein. The enzyme was optimally active at pH 6.0 (37 degrees C), and had apparent Km values of 40 and 88 microM for ATP and GTP respectively. The enzyme was not stimulated by cAMP or cGMP. Mg2+ was required for maximal activity. The reaction was inhibited by free Ca2+, and non-selectively by Na+, K+, and NH4+.

Animals↗

Sex-dependent differences in phenobarbitone-induced oestradiol-2-hydroxylase activity in rat liver.

Oestradiol-2-hydroxylase (E2-OH) activity was measured in live and brain microsomes of 6-8-week-old Wistar rats. Phenobarbitone (75 mg/kg daily for 3 days) significantly increased enzyme activity in the liver of males and females, but there were striking differences between the two sexes. In males the enzyme activity was increased by 37% over control values and in females by 200%. The total microsomal cytochrome P-450 content was increased by 75% in males and by 82% in females. the apparent Michaelis constant (Km) of E2-OH for 17 beta-oestradiol in untreated males (9.8 microM) and females (9.2 microM) did not differ significantly. Phenobarbitone treatment, however, tended to reduce the apparent Km in males (8.2 microM) and to increase it in females (18.7 microM). E2-OH activity was also detected in brain tissue of both sexes, but it was 50-200-fold lower than in the liver and was not increased by phenobarbitone.

Animals↗

[Mechanism of delta-aminolevulinic acid neurotoxicity].

The neurotoxicity of delta-aminolaevulinic acid (ALA), porphobilinogen (PBG), glutamic acid, gamma-aminobutyric acid and kainic acid was compared in order to investigate the possibility of a common neurotoxic mechanism. Only ALA (10 microM) and glutamic acid (1 mM) were toxic towards neurons in culture, as measured by cell survival after 5 days' exposure. 3H-kainic acid binds to striatal membranes with an equilibrium dissociation constant (KD) of 57 nM and the number of binding sites was found to be 20 pmol/g striatal tissue. However, neither of the porphyrin precursors could displace kainic acid from these binding sites. Kainic acid alone caused neuronal degeneration after intrastriatal administration, as determined by 3H-spiroperidol binding to striatal membranes. The porphyrin precursors ALA and PBG thus do not share a common neurotoxic mechanism with the well-known neurotoxin kainic acid.

Aminolevulinic Acid↗