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J J Walker

Publications and source records attributed to J J Walker.

At least 91 records · Page 5Linked to original sources

The role of cytokines in the production of prostacyclin and thromboxane in human mononuclear cells.

The aim of the present work was to study the regulatory effects of cytokines (TNF alpha, IL-1 beta and IL-2) on the production of the prostglandins (PGI2 and TXA2) from human mononuclear cells. Our major findings were: (1) TNF alpha, IL-1 beta and IL-2 were all able to induce PGI2 and TXA2 syntheses in mononuclear cells. (2) TNF alpha exerted a biphasic effect on prostaglandin production. The lower concentrations of TNF alpha enhanced prostaglandin synthesis while the higher concentrations did not. (3) TNF alpha had a positive effect after only a 30-minute incubation, whereas IL-1 beta and IL-2 required a 8-hour incubation to produce a significant effect. This suggests that the different mechanisms are involved in their actions. (4) The effects of cytokines on the production of PGI2 were greater than that on the production of TXA2. It is concluded that cytokines can not only regulate the production of prostaglandins but also change the pattern of their formation.

Cells, Cultured↗

Normal superoxide dismutase (SOD) gene in pregnancy-induced hypertension: is the decreased SOD activity a secondary phenomenon?

Reactive oxygen species (ROS) have been implicated in the pathogenesis of pregnancy-induced hypertension (PIH). A genetic factor is also thought to be associated with the disease. The aim of the present study was to investigate whether decreased superoxide dismutase (SOD) activity in PIH resulted from gene abnormalities. Fourteen patients with PIH were enrolled in the study. Normal pregnant women and normal nonpregnant women served as controls. Genomic DNA and mRNA were isolated from white cells and subjected to Southern and Northern blot analysis with a 600 bp CuZn-SOD probe. SOD activity was also determined in the white blood cells and red blood cells. The results showed that SOD activity was significantly reduced in patients with PIH compared to both control groups. There were no significant differences in the size of the CuZn-SOD gene and its expression between the patients with PIH and the controls. This study confirmed that there was a decreased SOD activity in PIH but revealed neither major structural changes in the genomic DNA nor mRNA size of CuZn-SOD. Our results suggest that the decreased SOD levels in PIH are not due to abnormalities in the CuZn-SOD gene and are an acquired phenomenon which occurs during the development of the disease.

Adult↗

Intracellular and extracellular antioxidant buffering levels in erythrocytes from pregnancy-induced hypertension.

Both intracellular (lysate thiol, lysate glutathione and lysate superoxide dismutase) and extracellular (plasma thiol, plasma glutathione and membrane thiol) antioxidant buffering levels were measured in red blood cells from patients with pregnancy-induced hypertension (PIH). We found the following. (1) The levels of plasma thiol and plasma glutathione in PIH women with proteinuria were markedly lower than that in the normal pregnancy. (2) The concentrations of lysate glutathione and superoxide dismutase in PIH women with proteinuria were significantly decreased compared with that in the normal pregnancy. (3) With the exception of plasma and lysate glutathione, all the tested antioxidant markers were not significantly different between PIH women without proteinuria and normal pregnancy. (4) There was no statistical correlation between antioxidant buffering level and BP in patients with PIH. We concluded that both extracellular and intracellular antioxidant buffering levels were decreased in patients with PIH, especially in those with proteinuria. The reduction of the antioxidant buffering level could account for several important pathophysiological features of PIH, such as the elevation of intracellular calcium, decreased red blood cell deformability and endothelial damage.

Adult↗

Production of prostacyclin and thromboxane A2 in mononuclear cells from preeclamptic women.

OBJECTIVE: Although the changes in prostacyclin and thromboxane A2 levels in preeclampsia have been well studied, little work has previously been done on mononuclear cells, and the cause of the changes in unclear. We determined the prostacyclin and thromboxane A2 production in mononuclear cells and investigated the effect of preeclamptic serum on this production. STUDY DESIGN: The production of prostacyclin and thromboxane A2 was measured by enzyme immunoassay in 16 normal pregnant women, nine preeclamptic women with proteinuria, and six preeclamptic women without proteinuria. Sera from these three groups of women were investigated to see whether the sera have any effect on prostaglandin production. RESULTS: The levels of thromboxane A2 in preeclamptic patients were found to be much higher than those of normal pregnancy, whereas the levels of prostacyclin tended to be lower. Such changes lead to a markedly increased ratio of thromboxane A2 to prostacyclin in preeclamptic patients. There was no difference in the levels of prostacyclin and thromboxane A2 between the preeclamptic patients with and without proteinuria. Serum from preeclamptic patients with proteinuria slightly reduced prostacyclin synthesis in normal pregnancy but significantly increased increased thromboxane A2 production, resulting in a ratio of thromboxane A2 to prostacyclin similar to that of preeclampsia. However, serum from preeclamptic patients without proteinuria failed to exert such effects. CONCLUSION: The imbalance between prostacyclin and thromboxane A2 occurs in mononuclear cells from preeclamptic women, and there is a factor(s) in proteinuric-preeclamptic serum to contribute, in part, to these changes. Our findings also suggested that the cause of abnormal prostaglandin production in preeclampsia was complicated and multifactorial.

6-Ketoprostaglandin F1 alpha↗

Prostacyclin, thromboxane and antioxidant levels in pregnancy-induced hypertension.

1. Plasma 6-keto-prostaglandin F1 alpha (6-keto-PGF 1 alpha, a major metabolite of prostacyclin), plasma thromboxane B2 (TXB2, a major metabolite of thromboxane A2) and five antioxidants (indirect markers of reactive oxygen species) namely, plasma thiol, erythrocyte lysate thiol, erythrocyte superoxide dismutase, plasma total glutathione and erythrocyte membrane thiol, were measured in 25 healthy non-pregnant women, 36 normotensive pregnant women and 35 women with pregnancy-induced hypertension (PIH). 2. The levels of TXB2 were significantly increased in normal pregnant women and PIH women with or without proteinuria compared with non-pregnant women. The concentrations of TXB2 in PIH women with proteinuria were higher than those without proteinuria (P < 0.05). 3. The levels of 6-keto-PGF1 alpha in healthy non-pregnant women and PIH women with or without proteinuria were significantly lower than that in normotensive pregnant women (all of three P < 0.01). There were no significant differences between healthy non-pregnant women and PIH women with and without proteinuria. 4. The ratio of TXB2 to 6-keto-PGF1 alpha was markedly elevated in PIH women with or without proteinuria compared with normotensive pregnant women and healthy non-pregnant women. The difference between PIH women with proteinuria and those without proteinuria was not significant (P > 0.05). 5. The levels of plasma thiol, superoxide dismutase and glutathione were significantly decreased in PIH women compared with normotensive pregnant women. 6. There were significant positive correlations between the levels of prostaglandins and antioxidant activity.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗

Quantitative 1H-NMR analysis of amniotic fluid.

Ten amniotic fluid samples (36-38 weeks gestation) are analysed by NMR spectroscopy. Of the species identified in the spectra, valine (mean 198 microM: SEM 57 microM), lactate (9.73 mM; 2.05 mM), alanine (689 microM: 115 microM), acetate (6.87 mM: 1.54 mM), citrate (363 microM: 59 microM), glucose (4.54 mM: 1.28 mM) indoxyl-sulphate (n = 4,270 microM), histidine (n = 6, 125 microM: 31 microM) and formate (n = 4, 92 microM) are quantified using standard addition. The factors governing the detection limits and lowest quantifiable amounts are discussed as are the extension of the work into in vivo magnetic resonance spectroscopy (MRS) in the clinic.

Amino Acids↗

Interleukin-2 receptor and ovarian cancer.

Interleukin-2 receptor (IL-2R) can be detected in serum. We estimated the IL-2R in the serum of 78 women, of whom 30 were diagnosed as having malignant ovarian tumours, five had non ovarian tumours, one had a negative second look laparotomy, 11 had benign ovarian tumours, three had uterine fibroids and 28 were age-matched controls. The results indicated that the serum IL-2R of these patients was significantly elevated in ovarian cancer patients compared to both controls (P < 0.0001) and benign ovarian tumours (P < 0.0002). There were no significant differences in IL-2R levels between stage of disease and degree of differentiation within the ovarian tumour group.

Adult↗

Interleukin 8.

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Amniotic Fluid↗

Efficacy of the somatostatin analog octreotide in the treatment of two patients with refractory diabetic diarrhea.

Two patients with severe refractory diabetes-related diarrhea are described. One patient had steatorrhea. Both responded to octreotide during a mean follow-up period of 7 months. The pathophysiology of diabetic diarrhea and the potential mechanism of action of octreotide are discussed. The only adverse side effect reported was hypoglycemia in one of the patients, which required a reduction of the insulin dose. Octreotide is a safe and effective agent for the treatment of refractory diabetic diarrhea.

Adult↗

A comparative study of intramuscular ketorolac and pethidine in labour pain.

A single dose block randomised double-blind study comparing intramuscular ketorolac, 50 mg of pethidine and 100 mg pethidine was carried out in multiparous women. Pain intensity and sedation effect were recorded at inclusion to the study, half hourly for the first 2 h, then hourly until 6 h after delivery. Maternal and neonatal side effects were noted including the Apgar scores and the baby's requirements for resuscitation. All three treatments are relatively ineffective in relieving labour pain. There was no difference in the analgesic efficacy between the two doses of pethidine but both doses of pethidine were statistically more effective compared with ketorolac. There was no difference in the retrospective assessment of the three groups or when comparison was made with the previous labour. A similar number of patients required further analgesia in each group. In all three groups, no adverse effect occurred in the mother or fetus. Maternal sedation and fetal depression were statistically less in the ketorolac group. Although ketorolac had inferior analgesic effect, its use was not associated with clinically significant sequelae and it showed a superior safety profile compared with either dose of pethidine. The study was not powerful enough to detect a difference between 50 mg and 100 mg of pethidine.

Adolescent↗

Immunological changes in normal pregnancy.

During pregnancy the mother must tolerate intra-uterine allogenic fetal tissue. Failure of this tolerance may cause spontaneous abortion. The immunological changes occurring in normal pregnancy are poorly understood. The aim of this study was to investigate the immunological changes occurring in pregnancy. Thirty women in the first trimester; 10 in the second and 10 in the third trimester of pregnancy were studied and compared to age matched non-pregnant controls. In normal pregnancy there was an increase in the total white cell count with no change in the lymphocyte count. There was a fall in total T cell numbers and activated T cell numbers, with no change in helper/inducer or suppressor/cytotoxic T cell numbers. [3H]Thymidine uptake in response to three different mitogens was increased. This implies an increase in potential for the cells to respond to mitogens. There was no change in interleukin-2 receptor levels, suggesting that despite this increased potential there was no general activation of the immune system. A rise in IgM and IgG was found after mitogen stimulation of peripheral blood lymphocytes, suggesting an increase in potential antibody production. These results demonstrate that lymphocytes from pregnant women have an increased potential rather than an increased activity.

Female↗

The effect of acute and chronic antihypertensive therapy on maternal and fetoplacental Doppler velocimetry.

Maternal and feto-placental Doppler flow velocity waveforms were studied during acute and chronic antihypertensive therapy in patients with pregnancy-induced hypertension. Eight primigravidae were acutely treated with oral nicardipine. Diastolic blood pressure fell at 30, 45 and 60 min after nicardipine. The uteroplacental systolic/diastolic ratio rose significantly at 30 min, but this change was no longer apparent at 60 min. Umbilical artery and maternal brachial artery systolic/diastolic ratios were unchanged. Fifteen patients with mild pre-eclampsia were chronically treated with oral pindolol. Diastolic blood pressure fell significantly within 24 h. The uteroplacental systolic/diastolic ratio rose 3 days after pindolol. Brachial artery or umbilical artery systolic/diastolic ratios were unchanged. A control group of 15 patients with untreated mild pre-eclampsia showed a significant rise in uteroplacental and umbilical artery systolic/diastolic ratios within 7 days of starting recordings. In patients with pregnancy-induced hypertension, acute and chronic blood pressure reduction was associated with no change in umbilical artery or maternal brachial artery Doppler systolic/diastolic ratios and a transient rise in the uteroplacental systolic/diastolic ratio.

Blood Pressure↗

The ultrasonic assessment of discordant growth in twin pregnancies.

Discordant fetal growth, as defined by an intertwin weight difference (calculated as a percentage of the weight of the larger twin) of 20% or more, is associated with an increased perinatal mortality and morbidity. In this study, the accuracy of ultrasound estimation of fetal weight by abdominal circumference and biparietal diameter measurements in 107 twin pregnancies was assessed. Discordant growth greater than 20% as measured by ultrasound was found to have a sensitivity of 5-25%, a specificity of 87-95%, a positive predictive value of 12-43% and a negative predictive value of 80-85% at gestations ranging from 28 weeks to term. ROC calculations showed that changes in the discordance level used did not improve the value of the test. These results indicate that ultrasound measurement of fetal weight alone cannot be used accurately to assess discordant growth in twin pregnancies.

Journal Article↗

Umbilical artery and uteroplacental velocimetry in pregnancies complicated by idiopathic low birthweight centile.

Umbilical artery and uteroplacental Doppler flow velocity waveforms were studied in 35 pregnancies complicated by idiopathic low birthweight centile. Thirty fetuses (86%) were below the 5th centile birthweight for gestation. Fifteen (43%) had an abnormal umbilical artery systolic to diastolic ratio. Uteroplacental waveforms were recorded in 29 of the 35 pregnancies and five (17%) showed an abnormal systolic to diastolic ratio. Abnormal uteroplacental systolic to diastolic ratios were associated with a significantly earlier gestational age at delivery and significantly more cesarean sections for fetal distress compared with normal uteroplacental systolic to diastolic ratios (p less than or equal to 0.01). The absence of umbilical artery end-diastolic frequencies was associated with a significantly earlier gestational age at delivery compared with the presence of umbilical artery end-diastolic frequencies (p less than 0.005). No differences in pregnancy outcome were observed comparing normal with abnormal amniotic fluid volume assessment. These findings suggest that Doppler studies may be useful in estimating the risk of adverse perinatal outcome for small for gestational age fetuses with no identifiable cause.

Blood Flow Velocity↗