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J J Walker

Publications and source records attributed to J J Walker.

At least 73 records · Page 4Linked to original sources
PubMed1997

Evidence for a familial pregnancy-induced hypertension locus in the eNOS-gene region.

Pregnancy-induced hypertension may be regarded as a manifestation of endothelial-cell dysfunction. The role of the eNOS gene in the development of a familial pregnancy-induced hypertension was evaluated by analysis of linkage among affected sisters and in multiplex families (n = 50). Markers from a 4-cM region encoding the eNOS gene showed distortion from the expected allele sharing among affected sisters (P = .001-.05), and the statistic obtained from the multilocus application of the affected-pedigree-member method also showed distortion (T[f(P)=sqrt(P)] = 3.53; P < .001). A LOD score of 3.36 was obtained for D7S505 when a best-fitting model derived from genetic epidemiological data was used, and LOD scores of 2.54-4.03 were obtained when various other genetic models were used. Estimates of recombination rate, rather than maximum LOD-score values, were affected by changes in the genetic parameters. The transmission-disequilibrium test, a model-free estimate of linkage, showed strongest association and linkage with a microsatellite within intron 13 of the eNOS gene (P = .005). These results support the localization of a familial pregnancy-induced hypertension-susceptibility locus in the region of chromosome 7q36 encoding the eNOS gene.

Adult↗
PubMed1997

The changing pattern of eclampsia over a 60-year period.

OBJECTIVE: To determine changes in the incidence and pattern of eclampsia within the same geographical area over a 60-year period. DESIGN: A retrospective, descriptive study of 1259 consecutive women classified, at the time, as having had an eclamptic convulsion between the years 1931 and 1990. SETTING: A large city centre teaching hospital and the surrounding catchment area. MAIN OUTCOME MEASURES: The changes in the incidence and timing of the convulsion and the outcomes for the mother and baby. RESULTS: Over the study period, the incidence of eclampsia fell by more than 90%, from 74.1/10,000 in the 1930s to 7.2/10,000 in the 1980s. Most of the reduction occurred over the first four decades, with little change in the last 20 years. Overall, 44% of the cases of eclampsia occurred in the antenatal period, 33% intrapartum and 23% postpartum. Since the biggest decreases were seen in the incidence of antenatal and particularly intrapartum eclampsia, there has been a relative increase in the proportion of eclampsia occurring postpartum. Maternal death from eclampsia occurred in 15.1% of cases between 1931 and 1940, 13.4% between 1941 and 1950, but fell dramatically to < or = 3.9% after 1950. There has been no maternal death since 1964. Apart from the first decade, postpartum eclampsia was associated with significantly less risk of death to the mother throughout the study period. Perinatal death rate has fallen steadily from 432.6/1000 cases of eclampsia between 1931 and 1940 over the first three decades, to 168.7/1000 between 1961 and 1970. There has been little change since, although a lower proportion of neonatal deaths occurred as stillbirths. CONCLUSIONS: We found a significant reduction in both the incidence of eclampsia and associated morbidity in this population over the last 60 years. This has occurred in association with the introduction of the National Health Service, widespread antenatal care for all and a general improvement in health and welfare. Any further reduction in the incidence in the UK may be difficult to achieve. Since the incidence of eclampsia is now low, efforts should perhaps be directed at minimising the morbidity associated with severe pre-eclampsia rather than prevention of convulsions.

Adult↗
PubMed1997

Bacteriophage infection and multiplication occur in Pseudomonas aeruginosa starved for 5 years.

Bacteriophages specific for Pseudomonas aeruginosa and Escherichia coli were examined for their ability to multiply in stationary phase hosts. Four out of five bacteriophages tested, including E. coli bacteriophage T7M, were able to multiply in stationary phase hosts. The bacteriophage ACQ had a mean burst size of approximately 1000 in exponential phase P. aeruginosa hosts and 102 in starved hosts, with corresponding latent periods that increased from 65 to 210 min. The bacteriophage UT1 had a mean burst size of approximately 211 in exponential phase P. aeruginosa hosts and 11 in starved hosts, with latent periods that increased from a mean of 90 min in exponential phase hosts to 165 min in starved hosts. Bacteriophage multiplication occurred whether or not the hosts had entered stationary phase, either because the cultures had been incubated for 24 h or were starved. Significantly, bacteriophage multiplication occurred in P. aeruginosa, which had been starved for periods of 24 h, several weeks, or 5 years. Only one P. aeruginosa virus, BLB, was found to be incapable of multiplication in stationary phase hosts. These results reveal that starvation does not offer bacterial hosts refuge from bacteriophage infection and suggest that bacteriophages will be responsible for significant bacterial mortality in most natural ecosystems.

Environmental Microbiology↗
PubMed1996

Management of labour in an isolated rural maternity hospital.

OBJECTIVES: To evaluate the use of a maternity unit run by general practitioners and midwives, describing the outcome of labour in an unselected group of women and quantifying the contribution made by general practitioners. DESIGN: Retrospective population based review of obstetric patients who had access to an isolated rural maternity unit. SETTING: Rural area 120 km from a consultant maternity unit. SUBJECTS: 997 consecutive women delivered between January 1987 and May 1991. MAIN OUTCOME MEASURES: Mode of delivery and complications by place of booking and place of delivery; need for medical intervention and transfer. RESULTS: 530 women (53%) were booked for delivery in the rural unit; this group had a caesarean section rate of 3.8% and an unplanned transfer rate of 12.8% to the consultant unit in labour. Of the 462 who delivered in the low risk unit, 25 (5%) required a forceps delivery; postnatal complications requiring emergency medical support occurred in a further 33 (7%). CONCLUSIONS: Risk characterisation is possible, but medical support from general practitioners and obstetricians is required in almost a third of women at low risk for complications of delivery. Results of this study support the team approach to obstetric management but not the move towards isolated units without organised medical support.

Cesarean Section↗
PubMed1996

Care of the patient with severe pregnancy induced hypertension.

Pregnancy induced hypertension remains the largest cause of maternal death in the UK. This is often related to inadequate or incorrect care. Recent randomised studies have enabled evidenced based clinical practice to be directed to the management of this condition. This allows a logical stepwise management structure to be developed in each hospital to make sure all women at risk get the best care available. This starts with comprehensive antenatal care with close collaboration between all professionals involved, early referral to an outpatient daycare unit if hypertension develops or is suspected, early use of antihypertensive therapy to control blood pressure once the diastolic is persistently above 100 mmHg, the use of magnesium sulphate to control convulsions, delivery on the best day in the best way and careful fluid management after delivery. Postnatal care should also contain risk assessment to allow directed counseling to the women concerning subsequent pregnancies.

Anticonvulsants↗
PubMed1996

Tumour necrosis factor-alpha (TNF-alpha) gene polymorphism and expression in pre-eclampsia.

Pre-eclampsia is an endothelial disorder and TNF-alpha has fundamental effects on endothelial cells by several means, including altering the balance between oxidant and anti-oxidant, changing the pattern of prostaglandin production and affecting expression of several cell surface components. To determine whether TNF-alpha mRNA expression is increased in pre-eclamptic patients, leucocytes from pre-eclamptic patients, normal pregnant women and normal non-pregnant women were studied for TNF-alpha expression using a quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method. Using a model of 373A ABI Sequencer, TNF-alpha gene polymorphism was also analysed by GENESCAN and Genotyper software in order to explain the mechanism of abnormal TNF-alpha expression. Our results show that TNF-alpha mRNA expression is significantly elevated in pre-eclamptic patients compared with the other two control groups. The high expression of TNF-alpha may be associated with the TNF1 allele, whose frequency is markedly increased in pre-eclamptic patients. These observations are consistent with a major role for TNF-alpha in mediating endothelial disturbances, and suggest a key role for TNF-alpha in the development of pre-eclampsia.

Adult↗
PubMed1996

Recurrent miscarriage is associated with increased numbers of CD5/20 positive lymphocytes and an increased incidence of thyroid antibodies.

The aim of this study was to determine whether recurrent miscarriage (three or more miscarriages, no live children) was associated with an increased incidence of autoantibodies. Five groups were enrolled into the study; healthy non-pregnant women, healthy first-trimester pregnant women, women suffering spontaneous abortion, those undergoing termination of pregnancy and those with a previous history of miscarriage. The number of total B cells and the numbers of the antibody producing B cell subset CD5+/CD20+ were determined for each group. Samples were tested for anticardiolipin antibodies, antinuclear antibodies and thyroid microsomal and thyroglobulin antibodies. The results showed that compared to normal pregnancy or spontaneous abortion, recurrent miscarriage was associated with a significant increase in the number of CD5+/20+ positive cells (0.8 +/- 0.3 vs 0.5 +/- 0.1 vs 1.1 +/- 0.3 x 10(8)/l; p < 0.001). These women were also found to have a higher incidence of thyroid antibodies, with four out of the 11 patients being positive for thyroid microsomal antibodies. These results suggest that there may be an association between autoimmunity and recurrent miscarriage.

Abortion, Habitual↗
PubMed1994

Immunological changes in pregnancy-induced hypertension.

Aspects of T and B cell function were studied in women with pregnancy-induced hypertension (PIH) and normotensive pregnant women by determining the proliferation of peripheral blood mononuclear cells (PBMC) with or without stimulation by mitogens (PHA, ConA and PWM) and by determining IgG and IgM levels in the culture supernatant. The results showed that the proliferation of PBMC without mitogens was significantly increased in PIH women without proteinuria compared with normotensive pregnant women. In the presence of PHA, [3H]thymidine uptake in PBMC was statistically higher in PIH women both with and without proteinuria than that in normotensive pregnant women. ConA and PWM mitogen activities were not significantly different between PIH women and normotensive pregnant women. Compared with normotensive pregnant women, IgG production was significantly increased in PIH women with proteinuria but not in those without proteinuria. IgM production was not changed in PIH women. We concluded that immunologic responses in PIH women were increased rather than decreased. This increased immunologic activity is in accordance with some important changes seen in PIH, such as an increase in intracellular calcium, the presence of blood-borne mitogenic factor and a decrease in prostaglandin E series. These findings also support the hypothesis that PIH might result from the imbalance between fetal antigenic load and maternal production of immunologic blockade.

Adult↗
PubMed1994

The role of protein tyrosine phosphorylation in integrin-mediated gene induction in monocytes.

Integrin-mediated cell adhesion, or cross-linking of integrins using antibodies, often results in the enhanced tyrosine phosphorylation of certain intracellular proteins, suggesting that integrins may play a role in signal transduction processes. In fibroblasts, platelets, and carcinoma cells, a novel tyrosine kinase termed pp125FAK has been implicated in integrin-mediated tyrosine phosphorylation. In some cell types, integrin ligation or cell adhesion has also been shown to result in the increased expression of certain genes. Although it seems reasonable to hypothesize that integrin-mediated tyrosine phosphorylation and integrin-mediated gene induction are related, until now, there has been no direct evidence supporting this hypothesis. In the current report, we explore the relationship between integrin-mediated tyrosine phosphorylation and gene induction in human monocytes. We demonstrate that monocyte adherence to tissue culture dishes or to extracellular matrix proteins is followed by a rapid and profound increase in tyrosine phosphorylation, with the predominant phosphorylated component being a protein of 76 kD (pp76). Tyrosine phosphorylation of pp76 and other monocyte proteins can also be triggered by incubation of monocytes with antibodies to the integrin beta 1 subunit, or by F(ab')2 fragments of such antibodies, but not by F(ab) fragments. The ligation of beta 1 integrins with antibodies or F(ab')2 fragments also induces the expression of immediate-early (IE) genes such as IL-1 beta. When adhering monocytes are treated with the tyrosine kinase inhibitors genistein or herbimycin, both phosphorylation of pp76 and induction of IL-1 beta message are blocked in a dose-dependent fashion. Similarly, treatment with genistein or herbimycin can block tyrosine phosphorylation of pp76 and IL-1 beta message induction mediated by ligation of beta 1 integrin with antibodies. These observations suggest that protein tyrosine phosphorylation is an important aspect of integrin-mediated IE gene induction in monocytes. The cytoplasmic tyrosine kinase pp125FAK, although important in integrin signaling in other cell types, seems not to play a role in monocytes because this protein could not be detected in these cells.

Benzoquinones↗
PubMed1994

The prevalence of lupus anticoagulant and anticardiolipin antibodies in women with a history of first trimester miscarriages.

OBJECTIVE: To determine the prevalence of lupus anticoagulant and raised anticardiolipin antibodies in women with a history of two or more miscarriages in the first trimester of pregnancy. DESIGN: A prospective study of lupus anticoagulant and anticardiolipin antibody levels in unselected women with a history of two or more first trimester miscarriages. SETTING: The prepregnancy clinic and miscarriage antenatal clinic in a tertiary referral centre. SUBJECTS: Two hundred and forty-three women, of whom 113 (47%) had a past history of two miscarriages, and 130 (53%) had three or more miscarriages. MAIN OUTCOME MEASURES: Quantitative detection of lupus anticoagulant and anticardiolipin antibodies; number of miscarriages in women in the normal and the abnormal groups. RESULTS: Of the 243 women tested, 41 (16.8%) had an abnormality of lupus anticoagulant or anticardiolipin antibodies. This was significantly different from the normal population as previously reported. Sixteen women (6.6%) were positive for lupus anticoagulant, 20 (8.2%) had elevated anticardiolipin antibodies, and five (2%) had both abnormalities. The most frequently positive test for lupus anticoagulant was the dilute Russel viper venom time, and IgG was the most frequently elevated anticardiolipin antibody. Of the women with a history of only two miscarriages, 15% had an abnormality of lupus anticoagulant or anticardiolipin antibodies, compared with 18.5% of those with a history of three or more miscarriages. This did not reach statistical significance. There were 117 (48%) primary miscarriers and 126 (52%) secondary miscarriers. Of the primary miscarriers, 17% had an abnormality, compared to 18% of the secondary miscarriers. CONCLUSIONS: These findings provide further evidence of an association between lupus anticoagulant and anticardiolipin antibodies and early pregnancy loss. It is not known if these are the cause of miscarriage, markers for miscarriage, or if antiphospholipid antibodies develop as a result of a noncontinuing pregnancy. Further studies comparing various treatments are required before women with these antibodies can be optimally managed.

Abortion, Spontaneous↗
PubMed1994

The cell adhesion molecule, VCAM-1, is selectively elevated in serum in pre-eclampsia: does this indicate the mechanism of leucocyte activation?

OBJECTIVE: To determine whether circulating levels of cell adhesion molecules, markers of endothelial damage and leucocyte activation, were increased in pre-eclampsia. DESIGN: Serum was prepared from peripheral venous blood and stored at -70 degrees C. The cell adhesion molecules, VCAM-1, E-Selectin and ICAM-1, were measured by ELISA. SETTING: Department of Obstetrics and Gynaecology, Royal Infirmary, Glasgow. SUBJECTS: Sixteen primigravid women with pre-eclampsia were recruited for the study. The preeclampsia group were compared with 18 healthy primigravid women with uncomplicated pregnancies. RESULTS: The pre-eclamptic group had significantly higher serum levels of the cell adhesion molecule VCAM-1 (t = 3.673; P < 0.001). There were no significant differences in the adhesion molecules ICAM-1 or E-Selectin. CONCLUSIONS: Endothelial damage and dysfunction are common to all the pathological features of pre-eclampsia. This study shows that concentrations of cell adhesion molecules, which indicate leucocyte-endothelial attachment and activation, are elevated in the serum of patients with pre-eclampsia. Such increases in soluble circulating cell adhesion molecules may reflect increased expression of these molecules on the endothelium and thereby explain the mechanism for leucocyte activation in pre-eclampsia.

Adult↗
PubMed1994

Renin gene restriction fragment length polymorphisms do not show linkage with preeclampsia and eclampsia.

OBJECTIVE: To investigate linkage between the renin gene restriction fragment length polymorphisms in families with a history of preeclampsia/eclampsia. METHODS: Nine Icelandic families with at least three affected females in two or three generations were investigated. DNA from lymphocytes was digested with the endonuclease restriction enzyme Bgl I and restriction fragments were transferred by Southern Blotting. Hybridisation was effected with the 32P-oligonucleotide-labeled diallelic genomic probe pHRnX 0.8. LOD scores were calculated by the Liped program for two forms of inheritance patterns. Affected sib pairs were analysed. RESULTS: Frequencies of the 9.0 kb and 5.0 kb alleles were 0.67 and 0.33, with no significant differences between affected females and spouses and combined LOD scores of -2 for recombination values of 3%. Allele sharing in affected sibs was not different from the expected random assortment. CONCLUSION: The linkage analysis provides evidence to exclude alteration of the renin gene in pregnancy as being directly responsible for the manifestations of preeclampsia or eclampsia in these families.

Alleles↗