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Biomedical subjects

J K French

Publications and source records attributed to J K French.

At least 73 records · Page 4Linked to original sources
PubMed1990

Simvastatin therapy for hypercholesterolaemia in patients with coronary heart disease.

The efficacy of simvastatin therapy for hypercholesterolaemia was evaluated in 26 patients with coronary heart disease, 20 of whom had undergone coronary artery bypass grafting. Simvastatin reduced total- and low-density lipoprotein (LDL) cholesterol from 8.3 to 5.1 (38%) and 6.3 to 3.3 mmol/L (48%) respectively, p less than 0.001; high-density lipoprotein (HDL) cholesterol increased from 1.19 to 1.24 mmol/L, p = NS. The changes in apoproteins A1 and B paralleled those of HDL- and LDL-cholesterol. There were no clinically important adverse effects. We conclude that simvastatin is effective lipid lowering therapy and can be used safely, in the short term, in patients with coronary heart disease.

Anticholesteremic Agents↗
PubMed1990

Phorbol 12-myristate 13-acetate, A23187 and L-adrenaline inhibit phospholipid methylation in human monocytes and lymphocytes. Inhibition is independent of oxyradical production and phospholipid hydrolysis.

The Ca++ ionophore A23187 and phorbol 12-myristate 13-acetate (PMA) caused dose-dependent inhibition of phospholipid (PL) methylation in unfractionated mononuclear cells (MNC), monocytes, and lymphocytes as measured by incorporation of 3H-methyl-groups from [3H-methyl]-L-methionine into phosphatidylcholine (PC), dimethyl phosphatidylethanolamine (PE), and monomethyl PE. This inhibitory effect did not correlate with monocyte superoxide release and was unaltered by the presence of either catalase and superoxide dismutase or the NADPH oxidase inhibitor, diphenylene iodonium (DPI), indicating that oxyradical-mediated oxidation of methionine was not the major cause of inhibition of PL methylation. Furthermore L-adrenaline, which elevates cAMP and does not stimulate superoxide release, also inhibited PL methylation. Inhibition by PMA was not due to reduction in intracellular levels of methionine or S-adenosyl methionine. A23187 caused reduction of S-adenosyl methionine levels only at 1 microM, and had no effect at lower concentrations. Inhibition of PL methylation was shown not to be due to phospholipase A2-dependent hydrolysis of newly methylated PL. Attempts to reverse the inhibitory effect of either A23187 or PMA with the putative protein kinase inhibitors W-7 and H-7 were inconclusive. The mechanism of inhibition of PL methylation by A23187 and PMA remains unclear, but does not appear to be due to oxidation of methionine or hydrolysis of newly methylated PL.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1990

The effect of dietary fish oil supplement upon the content of dihomo-gammalinolenic acid in human plasma phospholipids.

Patients (n = 23) with definite or classical rheumatoid arthritis were given 18 g/day fish oil in gelatin capsules which provided 3.2 g/day EPA and 2.0 g/day DHA. The treatment period was 12 weeks followed by a 4 week washout period. Fish oil supplementation to the diet resulted in a substantial increase in the content of EPA and DHA in each of the plasma fractions examined (PL, TG, and CE). Little change was seen in the AA level of the TG and CE fractions but a modest decrease in AA was seen in PL. However the intake of fish oil caused a significant depression in the content of DGLA in the PL (p less than 0.005) and CE (p less than 0.01) fractions relative to baseline values. All changes had reverted to near baseline levels 4 weeks after dietary intervention. Since DGLA is the precursor of PGE1, which has been shown to be anti-inflammatory, our findings suggest that the anti-inflammatory effects of fish oil consumption could be mitigated by an associated reduction in DGLA.

8,11,14-Eicosatrienoic Acid↗
PubMed1988

Chloroquine and hydroxychloroquine inhibit multiple sites in metabolic pathways leading to neutrophil superoxide release.

The effect of chloroquine and hydroxychloroquine on human neutrophil polymorph superoxide (O2-) production stimulated either by opsonized zymosan, phorbol myristate acetate or fluoride was examined in vitro. Both drugs inhibited the response to all 3 stimuli in a dose and time dependent fashion. Inhibition of zymosan stimulated O2- release was only attributable in a minor degree to inhibition of expression of surface receptors (MO-1), and appeared to be mainly due to inhibitory effects on more distal components of the activation pathway. Possible mechanisms for the inhibition of fluoride and phorbol ester stimulated O2- release are discussed in the light of current understanding of metabolic pathways of neutrophil polymorph activation.

Cells, Cultured↗
PubMed1988

Clinical and biochemical effects of dietary fish oil supplements in rheumatoid arthritis.

In a double blind noncrossover study, dietary supplementation with fish oil (18 g/day), was compared with an olive oil supplement over a 12-week period in patients with rheumatoid arthritis receiving established conventional therapies. An improvement in tender joint score and grip strength was seen at 12 weeks in the fish oil treated group but not in the olive oil treated group. The more subjective measures of mean duration of morning stiffness and analogue pain score improved to a similar extent in both groups, although statistical significance was only achieved in paired analyses in the olive oil treated group. Production of leukotriene B4 by isolated neutrophils stimulated in vitro was reduced by 30% in the fish oil treated group and unchanged in the olive oil treated group.

Adult↗
PubMed1987

Calcium ionophore A23187 enhances human neutrophil superoxide release, stimulated by phorbol dibutyrate, by converting phorbol ester receptors from a low- to high-affinity state.

The calcium ionophore A23187 acted synergistically with phorbol dibutyrate (PDBu) to stimulate human neutrophil superoxide production. A23187 shortened the lag period and markedly increased the initial rate of neutrophil superoxide production induced by suboptimal concentrations of PDBu. 1 microM A23187 reduced the EC50 value for superoxide release from 56 to 8 nM PDBu. This effect of A23187 was correlated with enhanced binding of [3H]PDBu to its receptor and a reduction in the dissociation constant (Kd) from 27 to 10 nM, without altering the apparent total number of phorbol dibutyrate receptors. These actions of A23187 were abolished in the presence of EGTA or TMB-8, confirming a dependence on Ca2+.

Caenorhabditis elegans Proteins↗
PubMed1987

Uptake of chloroquine and hydroxychloroquine by human blood leucocytes in vitro: relation to cellular concentrations during antirheumatic therapy.

The accumulation of chloroquine and hydroxychloroquine in unfractionated mononuclear cells and in purified monocytes, lymphocytes, and neutrophil polymorphonuclear leucocytes (PMN) was measured in vitro. Accumulation of both drugs in leucocytes was time and dose dependent. Cellular levels comparable to those found during antirheumatic therapy were achieved by preincubation for 60 minutes with up to 0.1 mM chloroquine or hydroxychloroquine.

Arthritis, Rheumatoid↗
PubMed1987

Studies on the mechanism of inhibition of chemotactic tripeptide stimulated human neutrophil polymorphonuclear leucocyte superoxide production by chloroquine and hydroxychloroquine.

The effect of chloroquine and hydroxychloroquine on neutrophil superoxide release stimulated by the chemotactic tripeptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) was examined. Both drugs caused time and dose dependent inhibition of superoxide release but had no effect on equilibrium binding of [3H]FMLP to its receptor. Preliminary experiments suggest that these drugs may exert their inhibitory effect on superoxide release by inhibiting the FMLP stimulated hydrolysis of phosphoinositides.

Chemotaxis, Leukocyte↗
PubMed1987

Effects of piroxicam on superoxide generation, phospholipid methylation and leukotriene production by human blood mononuclear cells.

The antiinflammatory agent piroxicam caused dose dependent inhibition of N-formylmethionyl-leucyl-phenylalanine (FMLP) induced monocyte superoxide release in vitro, but had no effect on the response to serum treated zymosan, phorbol myristate acetate or the calcium ionophore A23187. The inhibitory effect on the superoxide response to FMLP correlated with inhibition of specific 3H-FMLP binding. Piroxicam did not inhibit production of leukotriene B4 stimulated either by A23187 or by FMLP with arachidonic acid. Piroxicam did not inhibit phospholipid methylation. Since piroxicam inhibited neither the superoxide response to zymosan, a membrane receptor mediated response, nor phospholipid methylation, the effect of this drug on FMLP receptor binding appears to be relatively selective. Our data also exclude a significant effect of piroxicam on activation of protein kinase C or the NADPH oxidase of mononuclear phagocytes.

Dose-Response Relationship, Drug↗
PubMed1986

Differential effects of mepacrine, chloroquine and hydroxychloroquine on superoxide anion generation, phospholipid methylation and arachidonic acid release by human blood monocytes.

The 4-aminoquinolines chloroquine (CQ) and hydroxychloroquine (HCQ), and previously the 9-aminoacridine mepacrine (quinacrine) (MP), have been widely used in the treatment of inflammatory disorders such as rheumatoid arthritis and systemic lupus erythematosus. Their effects are believed to be mediated through phagocytic cells but the precise biochemical basis remains uncertain. We have investigated the effects of these drugs on monocyte superoxide anion (SO) generation elicited by 5 different stimuli-opsonised zymosan (STZ), FMLP, A23187, TPA and fluoride--and sought correlations with effects on two processes which have been linked with monocyte activation, namely arachidonate (AA) release and transmethylation of phosphatidyl ethanolamine (PE) to phosphatidylcholine (PC). In all experiments conditions were adjusted to achieve leucocyte concentrations of drug comparable to those found during in vivo therapy. Neither CQ nor HCQ had any marked effect on SO release induced by TPA, A23187 or fluoride ion, excluding a significant effect on protein kinase C (PKC), calmodulin-dependent kinase(s) or the membrane-bound, superoxide generating NADP(H) oxidase. In contrast MP inhibited the response to TPA and A23187. Each drug also had different effects on surface receptor-dependent responses; thus HCQ inhibited FMLP- but not STZ-induced SO release, whereas CQ and MP inhibited the response to both stimuli. Each drug also displayed different effects on AA release and phospholipid (PL)-methylation; MP and HCQ, but not CQ, inhibited STZ-stimulated AA release while MP and CQ but not HCQ inhibited basal rates of PL-methylation in mononuclear cells (MNC). However, only MP inhibited PL-methylation in an enriched monocyte population. We conclude that despite their close structural similarity, MP, CQ and HCQ each have different metabolic effects and their actions cannot simply be attributed to inhibition of lysosomal functions. Other possible mechanisms of action are discussed. The selective effects of each drug also provide further evidence for multiple pathways of monocyte activation.

Arachidonic Acid↗
PubMed1986

Milk alkali syndrome following over-the-counter antacid self-medication.

Four patients with mild, asymptomatic chronic renal failure became severely hypercalcaemic while taking over-the-counter antacids with daily calcium loads of only 4-8 g. Renal impairment carries an increased liability to this syndrome. Persistent elevation of serum parathyroid hormone levels led to parathyroid exploration in two of the cases, and normal glands were found. In retrospect the hormone levels were appropriate to the degree of renal impairment. Over-the-counter antacid preparations should carry dosage warnings to avoid the possibility of hypercalcaemia.

Aged↗
PubMed1985

Lumbar puncture in subarachnoid haemorrhage: yes or no?

Seventy patients admitted to the Auckland hospitals suffering from acute subarachnoid haemorrhage without major neurological deficits underwent diagnostic lumbar puncture. No patients showed immediate deterioration. Where the clinical indication exists and the circumstances require, lumbar puncture continues to be an appropriate investigation in establishing the diagnosis of subarachnoid haemorrhage.

Humans↗
PubMed1985

Isolated angiitis of the central nervous system.

Angiitis confined to the central nervous system is a rare disorder in which inflammation and consequent irregular narrowings of medium-sized cerebral arteries are prominent. Clinical and radiological features in 3 patients with this condition are described. All patients responded to either steroid or steroid plus azathioprine therapy.

Adult↗
PubMed1979

The reaction of menadione with haemoglobin. Mechanism and effect of superoxide dismutase.

1. Menadione was found to react with both the haem groups and the beta-93 thiol groups of haemoglobin. 2. It oxidized the haem groups of oxyhaemoglobin, giving mainly methaemoglobin and a smaller amount of haemichrome. The reaction rate was decrease in the presence of catalase and markedly accelerated in the presence of superoxide dismutase. It is proposed that the overall reaction involves the initial reversible formation of methaemoglobin and the semiquinone, and that the effect of superoxide dismutase is to prevent the reverse reaction, by removing superoxide and hene O2-. E.s.r. evidence for the information of the semi-quinone and its reactions is presented. 3. The reaction of menadione with the beta-93 thiol groups of haemoglobin appeared to be similar to that with other thiols, forming the 3-thioether derivative of menadione, but it was also accompanied by reduction of methaemoglobin. This reduction was prevented by superoxide dismutase, but appeared to be caused by the semiquinone radical, which was produced as an intermediate. 4. Reduced glutathione functioned only to a limited extent as a scavenger of the menadione semiquinone. Its main reaction was directly with menadione to form the thioether. Ascorbate was a more efficient scavenger, and accelerated the oxidation of oxyhaemoglobin by menadione. 5. The significance of these findings in relation to menadione-induced erythrocyte haemolysis is discussed.

Catalase↗