Biomedical subjects

J N Bulmer

Publications and source records attributed to J N Bulmer.

At least 73 records · Page 4Linked to original sources

PubMed1995

Maternal levels of serum-soluble CD8 and IL-2R are not significantly elevated in idiopathic preterm labour.

OBJECTIVE: To search for evidence of immune activation in idiopathic preterm term labour by measuring the soluble markers of T cell activation, CD8 (sCD8) and interleukin-2 receptor (sIL2R). DESIGN: Serum sCD8 and sIL-2R were measured by commercial ELISA in subjects undergoing idiopathic preterm labour (PTL; n = 15) and normal term labour (TL; n = 17). Two gestationally equivalent non-labouring groups were also included representing preterm (PTC; n = 10) and term (TC; n = 10) controls. Possible delayed responses in soluble activation markers were monitored in blood samples taken 48 h after delivery in both labouring groups (PTLp; n = 9: TLp; n = 9). RESULTS: (1) Excluding the 48 h postpartum samples, no statistically significant differences were revealed following a Kruskall-Wallis analysis of variance (ANOVA) for levels of sIL-2R (P = 0.093) and sCD8 (P = 0.098). Including the postpartum samples, however, gave statistically significant differences for each (sIL-2R: P = 0.033; sCD8: P = 0.006). (2) No statistically significant difference was revealed by direct comparison of the two labouring groups alone (Wilcoxon-Mann-Whitney test: P > 0.05). (3) Significantly lower levels of sCD8 were found in the PTL subgroup which had histological evidence of inflammation (Wilcoxon-Mann-Whitney: P = 0.003). CONCLUSIONS: Statistical analysis of our data suggests that idiopathic preterm labour is not commonly associated with significant elevations in circulating sCD8 or sIL-2R levels compared with normal term labour. Where significant changes in the levels of these markers do arise, our evidence points to a delayed effect of labour per se rather than infection as the most probable cause.

Analysis of Variance↗

PubMed1995

Endometrial leukocyte subpopulations in women with endometriosis.

The aim of this study was to investigate whether the endometrium of women with endometriosis differs immunologically from the endometrium of normal fertile women. Endometrial biopsies were obtained from 18 normal fertile women who were requesting sterilisation or reversal of sterilisation and 21 infertile women who had laparoscopically diagnosed pelvic endometriosis. The endometrial biopsies were obtained from both groups during the either early, mid or late luteal phase of the menstrual cycle. A panel of 11 monoclonal antibodies and immuno-histochemical techniques were employed to characterise the endometrial stromal leukocytes in frozen sections. Image analysis was used for semi quantitation of leukocytes. In both groups, the number of endometrial granulated lymphocytes (CD56+ CD38+ cells) and macrophages (CD68+ cells) increased significantly between the early and late luteal phase of the menstrual cycle. Compared with fertile controls, women with endometriosis had fewer T-suppressor/cytotoxic (CD8+) cells and endometrial granulated lymphocytes but more T-helper/inducer (CD4+) cells, CD68+ cells and CD16+ cells. None of these differences reached a statistically significant level. This study has shown that the endometrial lymphoid tissue of women with endometriosis does not differ qualitatively or quantitively from that of normal fertile controls. However, functional differences of endometrial leukocytes between the two groups cannot be excluded.

Adult↗

PubMed1995

Immunohistochemical characterization of proliferation, oestrogen receptor and progesterone receptor expression in endometriosis: comparison of eutopic and ectopic endometrium with normal cycling endometrium.

Recent studies examining oestrogen and progesterone receptor status and the proliferative activity of endometriotic lesions have produced conflicting reports. This study aimed to clarify the receptor status and proliferative activity of eutopic and ectopic endometrium from women with endometriosis and endometrium from normal women. Progesterone and oestrogen receptor expression and proliferative activity were studied in eutopic and ectopic endometrium from 30 women with endometriosis and in endometrium from 30 normal cycling women using microwave-pretreated paraffin-embedded sections stained with an avidin-biotin peroxidase technique. Progesterone and oestrogen receptor expression in the control endometrium did not differ from that of eutopic endometrium from women with endometriosis. Oestrogen receptor expression in ectopic endometrium increased from the proliferative to the late secretory phase. Epithelial progesterone receptor expression decreased during the cycle. Oestrogen receptor expression in both epithelium and stroma of ectopic endometrium was significantly higher than in eutopic endometrium throughout the cycle. In contrast, stromal progesterone receptor expression tended to be reduced in ectopic endometrium compared with eutopic tissue. Epithelial progesterone receptor expression was increased in ectopic endometrium but only in the late secretory phase. Although proliferative activity in the epithelium of control and eutopic endometrium was reduced from the proliferative to the late secretory phase, stromal activity did not vary. The proliferative activity in ectopic endometrium remained low and constant throughout the cycle. In the proliferative and early secretory phases, the proliferative activity of eutopic endometrium was increased compared with ectopic endometrium, but in the late secretory phase, levels were comparable. These findings challenge previous reports which have suggested that oestrogen receptors are reduced in ectopic tissue. This may have clinical implications for the development of novel treatments for endometriosis.

Case-Control Studies↗

PubMed1995

Non-syncytial sources of fetal DNA in transcervically recovered cell populations.

We have previously shown that fetal DNA can be detected in swabs and flushings obtained from the lower uterine pole prior to the termination of pregnancy. The presence of syncytiotrophoblast vesicles in transcervically retrieved samples suggested that this distinctive placental tissue was an abundant source of fetal DNA and a valuable resource in prenatal diagnosis strategies. In a more extensive study involving 150 terminations of pregnancy between 7 and 17 weeks gestational age, 29% of transcervically retrieved samples contained visible syncytial vesicles. Flushing of the uterine pole more frequently contained syncytia than direct aspiration (39% compared with 26% of samples) but this difference was not statistically significant. No samples > 14 weeks gestational age contained syncytia. Polymerase chain reaction analysis using Y-sequence specific-nested primers indicated the presence of fetal DNA in the absence of intact syncytial vesicles. We therefore examined samples by in-situ hybridization using Y-specific DNA probes. Positive labelling was observed in syncytial vesicles where present and in clumps of unidentified fetal cells. In addition, high numbers of naked nuclei were labelled in samples devoid of syncytia. These isolated nuclei are possibly derived from disrupted syncytia, and may be an important and hitherto overlooked contributory factor in fetal material which collects at the lower uterine pole.

Cervix Uteri↗

PubMed1995

Relationships between maternal malaria and malarial immune responses in mothers and neonates.

Immune responses of 97 Gambian women and their neonates were studied. New methods distinguished between active and previous placental malaria, were used to examine relationships between maternal malaria and neonatal immune responses. Many placentas (61%) had active or previous malarial infection. Maternal and cord malarial IgG levels correlated (P < 0.001). Malarial IgG was raised in cord blood in active placental malaria; IgM was not detected. Mean lymphoproliferation and the proportion of responders to soluble P. falciparum antigens (F32) and conserved regions of p190 expressed on trophozoites and schizonts (190L and 190N) were higher in neonates than mothers. There was no clear relationship between maternal malaria and neonatal mean lymphoproliferation to malarial antigens, although fewer neonates responded when mothers were actively infected. Matched maternal and neonatal lymphoproliferation responses did not correlate. However, first born neonatal lymphoproliferation to PPD and malarial antigens appeared lower than other neonates, in agreement with lower lymphoproliferation in primigravidae compared with multigravidae. Also in common with mothers, autologous plasma suppressed neonatal lymphoproliferation to PPD and malarial antigens, suggesting common immunoregulation. Higher cortisol or other circulating factors in first pregnancies may be implicated. The relevance of cell-mediated malarial immune responses detected at birth remains to be established.

Adolescent↗

PubMed1995

Placental heat shock proteins: no immunohistochemical evidence for a differential stress response in preterm labour.

The aetiology of idiopathic preterm labour remains obscure. The hypothesis that a stress response induced by low-grade bacterial infection in utero-placental tissues was investigated. Distribution of cognate and inducible isoforms of heat shock proteins (HSP) 70 kD, HSP 60 kD and HSP 90 kD were investigated in an immunohistochemical study of placental and decidual tissues before and after labour at varying gestations. Subjects were pregnant women undergoing singleton delivery after idiopathic preterm labour at less than 34 weeks' gestation (n = 23); spontaneous term labour at 37-42 weeks' gestation (n =24); preterm caesarean sections at less than 34 weeks' gestation for preeclampsia or intrauterine growth retardation (n=14); elective caesarean section at 37-42 weeks' gestation for cephalopelvic disproportion (n = 6). HSP expression was constant throughout the third trimester of pregnancy and did not change following the onset of labour, regardless of gestational age. A stress response in decidual tissues as determined by immunohistochemical analysis is apparently not associated with preterm labour.

Bacterial Infections↗

PubMed1995

Cyclo-oxygenase distribution in human placenta and decidua does not change with labour after term or preterm delivery.

Our objective was to determine, in an immunohistochemical study, the distribution of cyclo-oxygenase in placental and decidual tissues before and after labour at varying gestations. Subjects were pregnant women undergoing singleton delivery after idiopathic preterm labour at less than 34 weeks' gestation (n = 13); spontaneous term labour at 37-42 weeks' gestation (n = 11); preterm caesarean section at less than 34 weeks' gestation for pre-eclampsia or intrauterine growth retardation (n = 8); elective term caesarean section at 37-42 weeks' gestation for cephalopelvic disproportion (n = 7). Within the placental basal plate cyclo-oxygenase was localised in decidual stromal cells, extravillous trophoblast, and the apical border of villous syncytiotrophoblast, both before and after labour, regardless of gestational age. Within the placental membranes, decidual stromal cells showed intense cytoplasmic cyclo-oxygenase labelling and the chorion laeve strong membrane-associated cyclo-oxygenase reactivity before and after labour, regardless of gestational age. The amnion showed a heterogeneous staining pattern. After labour at term there was either positive cytoplasmic (5/10) or apical staining (5/10). Cyclo-oxygenase was demonstrated in an apical distribution in only 50% of the other subject groups. Cyclo-oxygenase is present in both decidua and placental tissues prior to the onset of labour at term. Demonstration of decidual and trophoblastic cyclo-oxygenase in both preterm and term subjects suggests that differential availability of cyclo-oxygenase is unlikely to be important in preterm delivery. Research into the withdrawal of inhibition or increased substrate availability is most likely to shed light on the signal pathways involved in the onset of labour, regardless of gestation.

Cell Membrane↗

PubMed1994

Human endometrial lymphocytes in normal pregnancy and pregnancy loss.

Leucocytes are a major component of decidualised endometrium in normal human pregnancy but despite numerous in vitro studies the in vivo role of the two major lymphocyte populations in implantation and early placental development remains uncertain. Although there is evidence from animal studies that NK cells play a role in pregnancy loss, further studies are required to clarify mechanisms of pregnancy loss in humans.

Abortion, Spontaneous↗

PubMed1994

Placental protein 14 in cycles with normal and retarded endometrial differentiation.

The purpose of this study was to investigate whether endometrium with retarded development differs, functionally, from endometrium with normal 'in-phase' development. Precisely timed endometrial biopsies were obtained from 24 women suffering from unexplained infertility at 4, 7, 10 and 13 days following the luteinizing hormone (LH) surge. Frozen sections were labelled with an anti-placental protein (PP) 14 monoclonal antibody using an avidin-biotin peroxidase technique and semi-quantification of endometrial PP14 was performed using a Quantimet 970 image analyser. Serum PP14 and saliva progesterone were measured for each patient. Data were analysed using one- and two-way analysis of variance. Normal and retarded endometrium were identified in 16 (group I) and eight (group II) women respectively. Both groups demonstrated a significant increase of the area of precipitate measured for PP14 from day LH + 4 to LH + 13. However, two-way analysis of variance showed that endometrial PP14 was significantly (P < 0.05) lower in the retarded endometrium group at LH + 10 and LH + 13. Serum PP14 was also significantly lower (P < 0.01) in women with retarded endometrial development at LH + 13. Women with normal endometrial development had a significantly higher (P < 0.05) concentration of cumulative saliva progesterone from LH + 3 to LH + 5. This study indicates that there are functional differences between normal and retarded endometrium. These differences may adversely affect uterine receptivity during implantation and the early placentation stage.

Adult↗

PubMed1994

Lymphoid tissue in the endometrium of women with unexplained infertility: morphometric and immunohistochemical aspects.

The purpose of this study was to investigate whether the endometrium of women with unexplained infertility differs in some immunological aspects from the endometrium of normal fertile women. Endometrial biopsies were obtained from 24 normal fertile women (group I) and 24 women suffering from unexplained infertility (group II) at 4, 7, 10 and 13 days following the luteinizing hormone (LH) surge. Endometrial granulated lymphocytes were assessed morphometrically in 2 microns resin sections. A panel of 11 monoclonal antibodies was employed to characterize the leukocyte subsets in frozen sections. Semi-quantification was performed with a Quantimet 970 image analyser. Data were analysed using one- and two-way analysis of variance. Compared with fertile controls, women with unexplained infertility had significantly lower numbers of CD8+ (T suppressor/cytotoxic) cells at each post-LH date. In contrast, the number of CD4+ (T helper/inducer) cells was significantly higher in group II. Throughout the luteal phase, infertile women had fewer CD56+ cells than normal fertile controls. The volume fraction of endometrium occupied by the nuclei of endometrial granulated lymphocytes did not alter with the cycle stage but the mean nuclear diameter and axial ratio decreased from LH+7 to LH+13. The differences observed in endometrial leukocytic subpopulations between fertile and infertile women may contribute to unexplained infertility probably by affecting the embryonic maternal dialogue during the implantation and early placentation period.

ADP-ribosyl Cyclase↗

PubMed1993

Beta-1 integrin cell adhesion molecules in the endometrium of fertile and infertile women.

In order to investigate whether the endometrium of women with unexplained infertility differs immunologically from the endometrium of normal fertile women, a panel of six monoclonal antibodies was used to characterize the presence of the beta 1-integrins or very-late-activation antigens (VLA) in the different endometrial compartments. Precisely timed endometrial biopsies at 4, 7, 10 and 13 days following the luteinizing hormone surge were obtained from 24 normal fertile women (group I) and 24 women suffering from unexplained infertility (group II). Frozen sections were labelled using an avidin-biotin peroxidase technique. VLA-1, VLA-2 and VLA-3 were present in glandular epithelium, stromal cells and vessels of both groups. VLA-4 was detected in group I but was absent from glandular and surface epithelium of group II. VLA-5 was not present in any of the specimens. VLA-6 was identified primarily in the basement membrane of vessels, glandular and surface epithelium in both patient groups. This study indicates that most beta 1-integrins are present in endometrium throughout the luteal phase of the menstrual cycle. The differences observed between the two groups may contribute to unexplained infertility.

Adult↗

PubMed1993

Subinvolution of the uteroplacental arteries: an immunohistochemical study.

Subinvolution of uteroplacental arteries is a well-recognized cause of hemorrhage in the postpartum period. Although the physiological changes in these arteries during pregnancy are well documented, the sequence of events in normal involution is largely unknown. A recent immunohistochemical study has raised the possibility of an abnormal interaction between maternal uterine cells and fetal trophoblast in subinvolution. An indirect immunoperoxidase technique was used to compare deposition of complement components and immunoglobulin in subinvoluted and normally involuted uteroplacental arteries in 25 cases of postpartum hemorrhage. Deposits of C1q, C3d, C4, and C9 were detected within the walls of normally involuted vessels, whereas deposition of C1q, C3d, and C4 was absent in subinvoluted vessels; C9 was detected only focally. Deposition of immunoglobulins G, A, and M mirrored those described for complement components. The results suggest that immunological factors are necessary for the process of normal involution of uteroplacental arteries and are deficient in subinvoluted vessels.

Arteries↗

PubMed1993

Placental malaria. I. Pathological classification.

Pregnant women are more likely to contract malaria than their non-pregnant counterparts. The aim of this study was to develop a simple classification system for the histopathological diagnosis of placental malaria infection applicable to placentas collected in field conditions. The placentas were classified into four groups depending on the presence and distribution of parasites and malaria pigment: active infection, active-chronic infection, past-chronic infection, not infected. The frequency of parasitized placentas (26.4%) was in keeping with the prevalence of placental parasitaemia documented in epidemiological studies. An additional 29.8% placentas showed pigment in fibrin only, indicating past-chronic infection. Chronic placental malaria infection was most common in primigravidae, possibly reflecting ineffective clearance of parasites from the placenta. Seasonal fluctuations between infection categories support progression of placental infection with delayed clearance of pigment from fibrin. The proposed classification system has allowed diagnosis of different categories of placental malaria infection by two independent observers. A standardized method of diagnosis may enhance understanding of placental pathology and reduced birth weight in malaria infection during pregnancy.

Adolescent↗

PubMed1993

Placental malaria. II. A semi-quantitative investigation of the pathological features.

Malaria in pregnancy is associated with reduced birth weight. Most pathological studies of placental malaria infection have focused on severe Plasmodium falciparum infection. In the present study of 121 placentas delivered in a rural area of The Gambia, malaria infection was diagnosed in tissue sections using a simple classification system and severity of pathology was ranked semiquantitatively. Deposition of malaria pigment in circulating cells was associated with active infections whereas pigment in fibrin was a feature of active-chronic infections. Primigravidae had higher levels of pigment at all sites, although these observations were not always significant. Thickening of the trophoblast basement membrane occurred in all infection categories but fibrinoid necrosis of chorionic villi was a feature of active and active-chronic infection. Both birth weight and placental weight were increased in infected placentas but widespread trophoblast basement membrane thickening was associated with decreased birth weight. Both birth weight and placental weight decreased with increased fibrinoid necrosis and cytotrophoblast prominence but the results were not significant. By this approach it has been possible to correlate placental pathology with different infection categories and to analyse the pathological features associated with decreased birth weight.

Adolescent↗

PubMed1993

Suppressed peripheral and placental blood lymphoproliferative responses in first pregnancies: relevance to malaria.

An understanding of processes that predispose pregnant women, and in particular primigravidae, to malaria infection is essential to improve malaria management in pregnancy. Lymphoproliferative responses to malaria-specific (F32, 190L, and 190N) as well as other antigens (Candida and purified protein derivative [PPD]) were examined in the peripheral and placental blood of 102 Gambian women at the time of delivery. The lymphoproliferative responses of placental cells were poor to all antigens compared with those of peripheral blood (Candida P < 0.001, PPD P < 0.001, F32 P = 0.008, 190L P = 0.003, and 190N P = 0.10). Reduced proliferative capacity of placental mononuclear cells may contribute to heavy parasite colonization of this organ. Proliferation to malarial and PPD but not Candida antigens was selectively suppressed in peripheral and placental blood of primiparae relative to multiparae (F32 P = 0.07, 190L P = 0.09, 190N P = 0.007, PPD P = 0.09). Autologous plasma contained factors that suppressed lymphoproliferative responses to the same series of antigens to which the primiparae responded poorly (F32 P < 0.001, 190L P < 0.001, 190N P < 0.001, PPD P = 0.03). Malarial antibody levels were comparable among women of different parities and between peripheral and placental blood. Primigravidae may be more susceptible to malaria because of unique physiologic factors, such as higher levels of circulating immunosuppressive corticosteroids (P < 0.001), rather than differences in levels of acquired immunity.

Adolescent↗

PubMed1992

Isolation of maternal mononuclear cells from placentas for use in in vitro functional assays.

Interest in immunoregulatory mechanisms within uteroplacental tissues, particularly in malarial infection during pregnancy, prompted us to develop a technique to extract maternal mononuclear cells from human term placentas. This method is described. The phenotypes of isolated cells were characterised for expression of CD45, CD3, CD4, CD8, CD14, CD15, CD68, CD22, CAM 5.2 and class II MHC antigens and compared with those in situ in frozen sections of the same placentas. Isolated mononuclear cell preparations were examined for contamination by fetal trophoblasts. Fetal leukocyte contamination appeared unlikely since histological sections of placental tissue, after the extraction of maternal leukocytes, showed intact chorionic villi with no disruption of fetal stem vessels. This technique produces preparations of maternal placental mononuclear cells which are representative of cells in situ, show minimal fetal cell contamination and are suitable for functional studies.

Antibodies, Monoclonal↗

PubMed1992

Endometrial lymphoid tissue in the timed endometrial biopsy: morphometric and immunohistochemical aspects.

OBJECTIVES: The purpose of this study was to provide a morphometric profile of endometrial granulated lymphocytes and to investigate qualitative and quantitative differences in leukocyte subsets in precisely timed luteal phase endometrial biopsies. STUDY DESIGN: Endometrial biopsies were obtained from 24 normal fertile women at 4, 7, 10, and 13 days after the luteinizing hormone surge. Endometrial granulated lymphocytes were assessed morphometrically in 2 microns resin sections. Eleven monoclonal antibodies were used to characterize leukocytes in frozen sections. Semiquantitation was performed with a Quantimet 970 image analyzer. Data were analyzed with one-way analysis of variance. RESULTS: CD8+ (T suppressor-cytotoxic) cells increased significantly from 4 to 7 days after the luteinizing hormone surge, whereas CD68+ macrophages increased from days 10 to 13. Lymphocytes with an unusual phenotype (CD56+, CD38+, CD2+) increased dramatically after 7 days. The volume fraction of endometrium occupied by the nuclei of endometrial granulated lymphocytes did not alter, but their mean nuclear diameter and axial ratio decreased from days 7 to 13. CONCLUSION: The morphometric findings indicate in situ proliferation of endometrial granulated lymphocytes rather than migration from the peripheral circulation. T lymphocytes, macrophages, and endometrial granulated lymphocytes increase significantly between certain stages of the luteal phase.

Adult↗

PubMed1992

Immune aspects of pathology of the placental bed contributing to pregnancy pathology.

Interest has recently focused on the role of the placental bed in the pathogenesis of a variety of pregnancy disorders. Considerable advances have been made in the understanding of the complex relationships between maternal and fetal trophoblast in the placental bed in normal pregnancy. Invasion of uterine spiral arteries by extravillous trophoblast effects the physiological changes required to accommodate increased blood flow to the fetoplacental unit. Control of trophoblast invasion may depend on intrinsic properties, such as production of proteolytic enzymes and expression of a non-classical class I MHC antigen, but maternal cells within decidua may also play a role. Leukocytes form a major component of human decidualized endometrium and in the first trimester consist of granulated lymphocytes, macrophages and T lymphocytes. Suggested roles for decidualized leukocytes include natural killer cell activity, cytokine secretion, antigen presentation and immunosuppression. Several pregnancy disorders, including pre-eclampsia and intrauterine growth retardation, may be due to abnormal maternofetal cellular relationships within the placental bed causing inadequate invasion of spiral arteries and acute atherosis. However, the role of immunological factors in the pathogenesis of these disorders is uncertain since deposition of immunoglobulins and complement has also been detected in spiral arteries in normal pregnancy. Placenta accreta may reflect undue invasiveness of trophoblast and immunohistochemical studies of subinvolution of uteroplacental arteries also suggest an abnormal maternofetal relationship in the placental bed. Although the in vivo role of decidual leukocytes is not known, studies of infertile endometrium have reported a deficiency of granulated lymphocytes, suggesting a possible role in early implantation and placentation. Granulated lymphocytes may also play a role in pregnancy loss. There have been considerable advances in understanding of the abnormal maternofetal relationships in the placental bed which can lead to pregnancy disorders. However, the aetiology and pathogenesis of the various clinical conditions is unlikely to be fully established until regulatory mechanisms in normal pregnancy are elucidated.

Abortion, Spontaneous↗