Heterozygotes for the delta F508 cystic fibrosis allele are not protected against bronchial asthma.
Explore the source record for details and available documents.
Alleles↗
Biomedical subjects
W A Liston
Publications and source records attributed to W A Liston.
Investigation of recurrent miscarriage.
Explore the source record for details and available documents.
Abortion, Habitual↗
Association between mannan binding protein deficiency and recurrent miscarriage.
The distribution of mannan binding protein (MBP) in blood donor sera was determined by enzyme-linked immunosorbent assay to establish normal concentrations. Abnormally low MBP concentrations were found in 16% (21 out of 135) of female partners and 14% (15 out of 108) of male partners of couples experiencing recurrent miscarriage, compared with < 5% of obstetrically normal controls (P < 0.005). This relationship was even stronger (9.5 versus 1.0%) and more significant (P < 0.002) when only subjects presumed to be homozygous for the mutant allele responsible for MBP deficiency were considered. By immunohistochemistry, MBP could be demonstrated in first trimester placenta. We suggest that low concentrations of MBP within the feto-placental unit increase susceptibility to fetal loss, possibly via an infection-induced placental cytokine imbalance.
Abortion, Habitual↗
Antenatal screening for cystic fibrosis: a trial of the couple model.
OBJECTIVE: To assess the delivery and acceptability of antenatal couple screening for cystic fibrosis. Carrier status was notified only when both members of a partnership had cystic fibrosis alleles and therefore a one in four risk of having an affected child. DESIGN: Mouthwash samples were tested when both partners participated. Results were returned only to positive couples. SETTING: Two large maternity hospitals in Edinburgh. SUBJECTS: Screening was offered to all couples who booked at one of the two hospitals. MAIN OUTCOME MEASURES: (a) The take up of screening, carriers and carrier couples identified, take up of prenatal diagnosis, and numbers of affected fetuses detected; (b) questionnaire measures of patient satisfaction and stress. RESULTS: Screening was offered to 8536 couples. 714 (8.4%) were regarded as ineligible, usually because of late booking or absence of a partner. 1900 (24.3%) of the remainder declined screening. Among the 5922 screened couples, four tested positive--that is, both partners were cystic fibrosis heterozygotes. All four elected to have prenatal diagnosis. There were three terminations of pregnancy because of an affected fetus, one couple having two successive pregnancies with affected fetuses. The participation rate was 76% for eligible couples (5922/7822) and 69% for all couples (5922/8536). Only 89 screened couples (1.5%) requested information on individual carrier status. No anxiety was detected among a cohort of the screened population, and 99% of questioned participants expressed satisfaction with the concept of couple screening. CONCLUSIONS: Antenatal couple screening is a satisfactory and acceptable way of screening for cystic fibrosis and has been adopted as routine in the two trial hospitals.
Anxiety↗
Gene therapy for cystic fibrosis: will it affect the uptake of prenatal carrier screening?
We report a study which examined whether the decision of 135 couples to accept prenatal cystic fibrosis (CF) carrier screening would be influenced by the advent of gene therapy. A majority (91 couples; 67 per cent) felt that gene therapy for CF would not influence their decision to be screened. Twenty-two couples (16 per cent) stated that they would decline to be screened and an equal number felt ambivalent. Even if the life expectancy of a CF sufferer were increased by gene therapy to normal, 78 per cent of couples would still wish to avail themselves of prenatal carrier screening. A majority of women who decline screening do so because they are opposed to termination of pregnancy. The availability of gene therapy could increase the proportion of couples who accept screening.
Cystic Fibrosis↗
Immunohistochemical localization of a beta-D-galactoside-binding lectin at the human maternofetal interface.
The 14 kD S-type lectin from human placenta may have a role in regulating the maternal immune response to fetal antigens. In this study, an immunoperoxidase technique was used to determine the distribution of the lectin at the human maternofetal interface. Tissue obtained during the first trimester of pregnancy and at term was used. The lectin was not detectable in either the villous syncytiotrophoblast or the underlying cytotrophoblast in first-trimester tissue, although some cells of the cytotrophoblast columns were reactive. It was also not detectable in villous or extravillous trophoblast populations at term. In contrast, strong reactivity was found in decidual stromal cells throughout gestation, and endometrial stromal cells were also positive. The lectin is, therefore, not a component of the immunosuppressive factors associated with syncytiotrophoblast membranes, but may have a role in either the decidual control of trophoblast migration or some functions unrelated to pregnancy, or both.
Chorionic Villi↗
Chlamydial serologic studies and recurrent spontaneous abortion.
OBJECTIVE: Our purpose was to investigate the putative association between immunoglobulin G antibodies to Chlamydia trachomatis and recurrent spontaneous abortions. STUDY DESIGN: Sera from 106 idiopathic recurrent aborters and 81 of their partners were tested for immunoglobulin G antichlamydial antibodies by whole inclusion immunofluorescence and compared with 3890 sera from a general antenatal population. Positive sera were further investigated by microimmunofluorescence to determine species (Chlamydia trachomatis, Chlamydia pneumoniae, Chlamydia psittaci) specificity. RESULTS: Twenty-six (24.5%) of women with recurrent spontaneous abortions had immunoglobulin G antichlamydial antibodies compared with 28 (34.6%) of their partners (chi 2 2.25, p < 0.05) and 788 (20.3%) of the general antenatal population (chi 2 1.16, p < 0.05), and the incidence of antibody positivity showed no trend with increasing number of previous abortions. Fourteen women with recurrent spontaneous abortions had antibodies to Chlamydia trachomatis, 12 to Chlamydia pneumoniae. The prevalence of antibodies to C. trachomatis did not differ significantly between women with recurrent spontaneous abortions and their partners, but the male partners had a significantly (p = 0.005) higher prevalence of Chlamydia pneumoniae antibodies. Chlamydial antibody seropositivity did not correlate with subfertility or subsequent pregnancy outcome. CONCLUSION: There is no association between immunoglobulin G antibodies to Chlamydia trachomatis and recurrent spontaneous abortion.
Abortion, Habitual↗
Remote pregnancy outcome after leukocyte immunotherapy.
Twenty-eight recurrent miscarriage patients who had live births after leukocyte immunization were followed. Sixteen had subsequent pregnancies (without further treatment). One pregnancy was terminated, and five others were spontaneously aborted. The live birth rate was therefore 10 of 15 (67%). Any benefit from leukocyte immunotherapy does not appear to be long lasting.
Abortion, Habitual↗
Evaluation of maternal serum immunoreactive inhibin as a first trimester marker of Down's syndrome.
BACKGROUND AND OBJECTIVE: Maternal serum immunoreactive inhibin has been shown to be significantly elevated in Down's affected pregnancies in the second trimester, suggesting that it may be useful in prenatal diagnosis. We have investigated whether it is similarly elevated in the first trimester. DESIGN: Stored maternal sera from women with Down's affected pregnancies and chromosomally normal control pregnancies were retrieved for analysis. These sera had been collected prospectively at either 11 or 12 weeks gestation as a routine antenatal booking procedure. SUBJECTS: From records, 11 women were identified as having had a Down's pregnancy. For each of these, 4 controls matched for gestation and duration-of-storage were also identified. MEASUREMENTS: Two different inhibin immunoassays were evaluated, one using an antibody raised against 31 kDa bovine inhibin and the other, a commercial two-site assay, using two antibodies directed against two distinct alpha-subunit epitopes. RESULTS: Neither assay detected a significant effect of gestation on serum inhibin levels. After combining the data from both gestations, no significant difference between the Down's samples and controls for either assay was detected. However, analysis of the data for each gestation separately revealed that one assay detected a significant difference in inhibin levels between Down's affected and unaffected pregnancies at 11 weeks gestation (mean +/- SEM 3186 +/- 195 vs 2020 +/- 172 ng/l, P < 0.01) but not at 12 weeks. The other, commercial, assay did not detect a significant difference at either gestation. In addition, there was poor association between the results of the two assays. CONCLUSIONS: These data suggest that immunoreactive inhibin, as detected by these assays, will not be useful as a late first trimester marker for Down's syndrome and also that these two assays detect different inhibin species in pregnancy serum.
Adult↗
Prenatal cystic fibrosis carrier screening: factors in a woman's decision to decline testing.
Among 2207 women eligible to be screened for cystic fibrosis (CF) carrier status during pregnancy, 325 (15 per cent) declined to be tested. Of these, 260 (80 per cent) answered a questionnaire soliciting their reasons for not participating. The main factor was opposition to termination of pregnancy, with 43 per cent being against termination for any reason and another 11 per cent against termination of a CF fetus. Other reasons given were partner's disapproval or non-participation (10 per cent), perceived risk of a CF child being low (7 per cent), the error rate of the test (6 per cent), and the generation of unacceptable levels of anxiety (5 per cent). Eleven women (4 per cent) said that they did not wish to be tested during pregnancy, but only six of these would have accepted screening at another time.
Abortion, Therapeutic↗
Influence of histocompatibility antigens in recurrent spontaneous abortion and its relevance to leukocyte immunotherapy.
A total of 108 couples with recurrent spontaneous abortion (RSA) were studied to investigate the possible influence of histocompatibility antigens (HLA) on their condition and its management. HLA-B18 was shown to be at a higher frequency in RSA women, but not significantly so after statistical correction. Just over half the RSA women shared two or more HLA-A, B or DR antigens with their partners (P < 0.01), but this group did not differ from the others in clinical or laboratory features, nor in subsequent pregnancy success rate. Leukocyte immunotherapy in which the donor shared at least one HLA-DR antigen with his partner was not associated with a significant improvement in subsequent pregnancy outcome compared with HLA-DR mismatched immunotherapy. HLA antibody production following leukocyte immunotherapy was influenced by both inoculum size and degree of HLA incompatibility, but had no effect on birthweight. Tissue-typing investigations are not indicated for individual RSA patients seeking advice or treatment.
Abortion, Habitual↗
Prenatal screening for cystic fibrosis: attitudes and responses of participants.
A screening programme to detect cystic fibrosis heterozygotes has been running in the antenatal clinics of a major Edinburgh maternity hospital for more than 2 years. A questionnaire was used to assess participants' knowledge of the genetics of the disorder and their attitudes to being screened. The respondents were 64 female heterozygotes and 63 of their non-heterozygous male partners, 101 female controls and 100 male controls. Although the two groups of controls received far less direct information than the carriers and their partners, all four groups were well informed about the genetics of cystic fibrosis and the significance of being a gene carrier. A majority of each group felt that adequate information had been given in the information leaflet, that they understood the purpose of screening and that they were glad to have participated. There was a consensus that CF carrier testing should be routinely offered to pregnant women, and also that it should be available in family planning clinics and GP health centres, but not in schools.
Attitude to Health↗
Prenatal screening for cystic fibrosis: psychological effects on carriers and their partners.
This study aimed to assess the psychological impact of screening for cystic fibrosis (CF) carrier status in a population of pregnant women. A cohort of 1798 women, who accepted the offer of testing before 18 weeks of pregnancy, filled in a self administered questionnaire seeking information on their perceived risk of carrier status and their emotional response, as well as a general health questionnaire (GHQ). Sixty-four women identified as CF carriers had partners who received a negative test result. This group and their partners were assessed, together with selected controls, on four further occasions: (1) on receiving the carrier's positive test result; (2) on receiving the partner's negative test result; (3) six weeks later; (4) six weeks after delivery. The instruments used were the GHQ and the Symptom Rating Test (SRT). When compared to control subjects, carriers showed a significant increase in generalised psychological disturbance which could be attributed specifically to symptoms of anxiety and depression during the period (average four days) that they awaited their partner's test result. On receiving a partner's negative test result, the carriers returned to control levels and maintained this equilibrium. Although there was no significant difference in generalised psychological disturbance between partners and their selected controls, partners did become significantly more anxious and manifested feelings of inadequacy while awaiting their own test result. Both male partners and male control subjects were more likely to become anxious if their partner was distressed.
Adolescent↗
Parental HLA sharing, feto-maternal compatibility and neonatal birthweight in families with a history of recurrent spontaneous abortion.
The mean birthweight of babies eventually born to couples with a history of recurrent spontaneous abortion (RSA) is allegedly lower if the parents have a high degree of HLA antigen sharing (Reznikoff-Etievant et al., 1991), but this relationship has not been independently confirmed. We have re-investigated this question by analysing data from 36 families. In 22 instances, we were able to relate birthweight directly to feto-maternal HLA compatibility for the first time in such families. We were unable to confirm any appreciable influence of paternal or feto-maternal HLA sharing on birthweight or placental weight and conclude that RSA families do not differ markedly from normal families in this respect.
Abortion, Habitual↗
Prenatal screening for cystic fibrosis.
Screening for carriers of CF (cystic fibrosis) is now possible but the best way of delivering such a service is unknown. In one model 4348 women attending antenatal clinics in an Edinburgh maternity hospital were invited to participate in a trial of prenatal screening. Mouthwash samples were tested for six CF alleles (85% of mutant genes) and when a woman was found to be a CF carrier her partner was also tested. Heterozygous couples were offered prenatal diagnosis. 609 (14%) women declined to enter the trial and another 574 (13%) were not screened, usually because of late booking. Among the remaining 3165 women there were 111 carriers of a CF gene (1 in 29). 4 of these 111 had carrier partners and these couples opted for prenatal diagnosis, the 1 pregnancy with an affected fetus being terminated. The psychological impact of screening was assessed by the general health questionnaire. There was a significant increase in stress at the time of the test result among women identified as carriers. However, this disappeared when their male partners tested normal and did not reappear later in the pregnancy. By providing time for couples to discuss the possibility of screening and by offering the test at a point (the antenatal booking clinic) at which most pregnant women are seen, this approach has advantages, provided that counselling is readily available.
Alleles↗
Prenatal cystic fibrosis carrier testing: designing an information leaflet to meet the specific needs of the target population.
A questionnaire was given to 180 patients in an antenatal clinic, who were eligible to enter a pilot trial of cystic fibrosis (CF) carrier testing, seeking their views on the information leaflet inviting them to participate; 161 patients (89%) entered the trial and 145 patients (81%) responded to the questionnaire, including 10 who did not enter the trial. Ninety-six percent of these found the leaflet easy to understand, and 97% of those partners who read the leaflet also found it easy to understand. Fifteen percent of patients thought the leaflet should give additional information. Most (92%) had heard of CF before reading the leaflet, television being the most common source of information. Although avoiding the birth of a child with CF was the reason most patients gave for wishing to be screened, almost as many were interested to know their carrier status. The decision to accept or decline testing was taken in conjunction with their partner by 63% of women. Of those who were screened, 59% stated that taking the test made them feel reassured, while 38% felt slightly apprehensive. It was concluded that, with a number of minor amendments, the leaflet met the specific needs of the target patient population.
Attitude to Health↗
Anti-paternal lymphocyte antibodies: a modified cellular enzyme-linked immunospecific assay (CELISA).
A cellular enzyme-linked immunospecific assay is described which is ideally suited to measuring the IgG antibody response to donor-specific lymphocyte infusions. The procedure is simple, sensitive, specific and objective.
Antibodies↗
An exclusion map for pre-eclampsia: assuming autosomal recessive inheritance.
Pre-eclampsia is a common complication of the second half of pregnancy that is associated with substantial fetal and maternal morbidity. Although the genetic basis of the disorder is unclear, epidemiological studies suggest that it occurs predominantly in the first pregnancies of women who are homozygous for a relatively common susceptibility gene. Using this epidemiological model, we have begun to construct an exclusion map by using both candidate genes and random DNA markers on a panel of two-generation families in which pre-eclampsia was rigorously defined. No evidence was found for linkage to the HLA region or to several genes implicated in the pathogenesis of hypertension.
Chromosomes, Human, Pair 1↗