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Biomedical subjects

J N Bulmer

Publications and source records attributed to J N Bulmer.

At least 55 records · Page 3Linked to original sources
PubMed1998

Inflammatory reactions in placental blood of Plasmodium falciparum-infected women and high concentrations of soluble E-selectin and a circulating P. falciparum protein in the cord sera.

To better understand reasons for increased susceptibility to malaria in pregnancy; and the interrelationships between maternal malaria, local immune reactions and the development of the fetus, concentrations of soluble interleukin-10 (IL-10), cytokine receptors, adhesion molecules, a Plasmodium falciparum protein, glutamate-rich protein (GLURP) and antibodies to P. falciparum rhoptry-associated protein-1 were measured among 105 Gambian women and their neonates. Peripheral blood concentrations of IL-10, soluble cytokine receptors and soluble adhesion molecules were found to be different from those concentrations measured in the placenta. Markers of inflammatory reactions: IL-10, sIL-2R, sIL-4R, and soluble tumour necrosis factor receptor I (sTNF-RI) were found in high concentrations in the placenta, indicating that inflammatory reactions take place in the placenta which has been regarded as an immunoprivileged site. Concentrations of soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intracellular adhesion molecule-1 (sICAM-1), potential adhesion receptors for malaria parasites, were associated with an active P. falciparum infection in the placenta although the associations did not reach significance. P. falciparum exoantigen, GLURP, was detected in cord blood indicating transplacental passage of malarial antigens. Concentrations of E-selectin were higher in cord blood samples compared with peripheral blood samples. This appeared to be associated with development of cord endothelial cells and not with P. falciparum infection.

Animals↗
PubMed1998

Expression of CD69 activation marker by endometrial granulated lymphocytes throughout the menstrual cycle and in early pregnancy.

Flow cytometry studies of first-trimester normal human decidua have proposed that a proportion of endometrial granulated lymphocytes (eGL), the predominant leucocyte population in early human pregnancy, co-express CD69. The purpose of this study was to investigate CD69 expression by immunohistochemistry throughout the menstrual cycle and in first-trimester human decidua and to determine whether CD69 expression by eGL is an in vivo characteristic or whether the antigen is acquired in vitro after tissue disaggregation and cell purification. Single immunoenzymatic and double immunofluorescence labelling of tissue sections, supplemented with double immunoenzymatic staining of purified eGL and flow cytometry, indicated that eGL do not co-express CD69 in situ but that they acquire the molecule in vitro after cell purification and culture.

Antigens, CD↗
PubMed1998

A community randomized controlled trial of insecticide-treated bednets for the prevention of malaria and anaemia among primigravid women on the Kenyan coast.

The effectiveness of insecticide-treated bednets (ITBN) in preventing malaria and anaemia among primigravidae living in Kilifi District, Kenya, was assessed by a randomized controlled trial between September 1994 and November 1995. All residents within 28 community clusters received ITBN in July 1993, whilst residents of another 28 clusters served as contemporaneous controls. All resident primigravid women with singleton pregnancies attending antenatal care at Kilifi District Hospital were eligible for recruitment. 503 primigravidae were recruited. 91.4% were anaemic antenatally (Hb < 11 g/dl): 91.0% from the intervention arm and 92.0% from the control arm. Severe anaemia (Hb < 7 g/dl) was found among 15.1% of intervention women and 20.1% of control women (P = 0.28). No significant differences were observed in reports of febrile illness or the presence of chloroquine in the serum or peripheral parasitaemia during the third trimester between the two groups. In the women delivering in hospital (n = 130), there was no association between placental malaria infection and the intervention: 77.4% of placentas from control women had evidence of past or active infection, compared with 72.0% of placentas from intervention women (P = 0.76). Similarly, in the women delivering in hospital, ITBN did not improve birth weight, and there were no differences in perinatal mortality between the two study groups. Despite ITBN having a great impact on paediatric severe malaria and mortality in this transmission setting, there was very little impact of ITBN on the morbidity associated with malaria infection in primigravidae. Alternative strategies are required to tackle this continued public health problem for pregnant women living in endemic areas similar to the Kenyan Coast.

Anemia↗
PubMed1998

Characterization of endometrial T lymphocyte subpopulations in spontaneous early pregnancy loss.

T lymphocyte subpopulations were compared in normal first trimester human decidua and in decidua associated with spontaneous abortion. Cryostat sections were labelled using a panel of monoclonal antibodies specific for CD3, CD8, CD4 and for the alphabeta and gammadelta heterodimers of the T cell receptor using an avidin-biotin complex peroxidase method. All the endometrial T cell subsets which have been demonstrated in normal early pregnancy were detected in similar numbers and proportions in spontaneous abortion. The findings suggest that adverse pregnancy outcome is not influenced by altered proportions of T cell subpopulations; nevertheless, the possibility remains that these cells may have an altered antigenic phenotype in spontaneous abortion which could contribute to pregnancy success or failure.

Abortion, Spontaneous↗
PubMed1998

Intraepithelial leukocytes in endometriosis and adenomyosis: comparison of eutopic and ectopic endometrium with normal endometrium.

Intraepithelial leukocytes (IEL) are recognized as an important component of most mucosal surfaces but have received scant attention in the human female reproductive tract. The aim of the present study was to characterize, quantify and compare IEL populations in normal endometrium (n = 30) and in eutopic and ectopic (endometriotic or adenomyotic lesions) endometrium from women with endometriosis (n = 30) or adenomyosis (n = 15) at different menstrual cycle phases in order to assess the role of IEL in these common but poorly understood disorders. IEL populations were examined in formalin-fixed, paraffin-embedded sections using a streptavidin-biotin-peroxidase complex technique and quantified in relation to epithelial cell numbers. IEL in control endometrium and eutopic endometrium in endometriosis and adenomyosis varied during the menstrual cycle, with CD45+, CD43+ and CD56+ cells increasing from the proliferative to the late secretory phase. IEL were elevated in surface compared with glandular epithelium in the proliferative and early secretory phases. Throughout the menstrual cycle there were no significant differences in IEL between eutopic and ectopic endometrium in adenomyosis. Endometriotic foci, however, contained elevated levels of CD45+, CD3+ and CD8+ cells and reduced numbers of CD56 + cells compared with the corresponding eutopic endometrium and these did not vary with menstrual cycle phase. In contrast, ectopic endometrium in adenomyosis showed some cyclical changes with CD56+ cells increasing significantly in the late secretory phase. It is possible these differences may play a role in the pathogenesis of endometriosis and the associated complications.

Antibodies, Monoclonal↗
PubMed1998

Apoptosis and bcl-2 expression in normal human endometrium, endometriosis and adenomyosis.

Apoptosis has been implicated in the pathogenesis of several diseases and is partly regulated by bcl-2, which blocks the apoptotic pathway and promotes cell survival. Apoptosis and bcl-2 expression were examined in paired eutopic and ectopic endometrium from women with endometriosis (n = 30 samples) or adenomyosis (n = 15 samples) and compared with control endometrium (n = 30 samples). Apoptotic cells were detected using the dUTP nick-end labelling (TUNEL) assay for DNA fragmentation; bcl-2 expression was demonstrated with a streptavidin-biotin peroxidase immunohistochemical technique. Apoptotic cells were rare in eutopic, ectopic and control endometrium; there were no significant differences between subject groups nor between eutopic and ectopic endometrium. Stromal bcl-2 expression increased in the late secretory phase in control and eutopic endometrium in endometriosis; double labelling studies revealed that most stromal bcl-2+ cells were leukocytes. Stromal bcl-2 expression in endometriotic foci was significantly increased compared with the paired eutopic endometrium, did not vary with menstrual cycle and included a significant population of non-leukocytic bcl-2+ stromal cells. In contrast, stromal bcl-2 expression in adenomyosis remained at low levels and did not show significant cyclical variation. Glandular epithelial bcl-2 expression also varied with menstrual cycle phase and peaked in the proliferative phase; in contrast, surface epithelial bcl-2 expression increased in the late secretory phase. Elevated stromal bcl-2 expression in ovarian endometriotic lesions could have implications for the growth and survival of ectopic endometrial tissue at these sites.

Apoptosis↗
PubMed1998

Functional studies of human decidua in spontaneous early pregnancy loss: effect of soluble factors and purified CD56+ lymphocytes on killing of natural killer- and lymphokine-activated killer-sensitive targets.

Inappropriate leukocyte activation and disturbance of the delicate cytokine balance within the uterus during early human pregnancy may initiate spontaneous abortion. The purpose of the present study was to assess whether decidual soluble factors from women suffering sporadic spontaneous early pregnancy loss could enhance the cytotoxic activity of peripheral blood lymphocytes (PBL), and to investigate the lytic activity of endometrial granulated lymphocytes (eGL) purified from decidua against natural killer (NK)- and lymphokine-activated killer (LAK)-sensitive targets. Decidual cell culture supernatants from sporadic spontaneous abortion cases did not have any effect on PBL cytotoxic activity against the NK-sensitive target cells K562. Endometrial GL purified from decidua of spontaneous aborters were unable to lyse the LAK-sensitive target cells Raji and, in contrast with eGL from decidua of first-trimester therapeutic aborters, approximately 50% of the cases also failed to kill K562 cells. These results do not provide evidence to implicate either cell-mediated or cytokine-mediated cytolytic mechanisms in early spontaneous pregnancy loss, thus strengthening the possibility that other damaging effects are operating. Nevertheless, the deficient cytotoxic activity in a proportion of spontaneous abortion decidua merits further investigation.

Abortion, Induced↗
PubMed1998

Apoptosis, bcl-2 expression, and proliferative activity in human endometrial stroma and endometrial granulated lymphocytes.

Human endometrial leukocytes undergo regular cyclical changes during the menstrual cycle, with a striking increase in the phenotypically unusual population of CD56+ CD16- endometrial granulated lymphocytes (eGLs) in the late secretory phase and early pregnancy. The factors that regulate this increase in eGL numbers are unclear; their unusual morphology, however, has led to the suggestion that they undergo apoptosis at the end of the menstrual cycle. Apoptosis, bcl-2 expression, and proliferative activity were examined in the stroma of normal cycling, progesterone-treated, and early-pregnancy endometrium. The expression of bcl-2 and the Ki67 proliferation marker by highly purified (> 98% CD56+) eGLs from endometrium during the menstrual cycle and from first-trimester decidua was also studied. Apoptotic cells were rarely observed in the endometrial stroma of any of the samples examined. Stromal bcl-2 expression, however, increased from the proliferative to the premenstrual phase, and double immunohistochemical labeling demonstrated large numbers of bcl-2+ CD56+ eGLs. In contrast, Ki67 expression was high in the endometrial stroma during the proliferative phase, fell during the secretory phase, and rose again premenstrually, because of expression by eGLs. Isolated CD56+ eGLs also showed high bcl-2 and Ki67 expression at the end of the menstrual cycle. Unlike premenstrual endometrium, progesterone-treated endometrium and first-trimester decidua contained few proliferating cells, expressed high levels of bcl-2, and showed no evidence of apoptosis. Thus, eGLs do not undergo apoptosis in premenstrual endometrium, and their regulatory mechanisms remain to be clarified.

Apoptosis↗
PubMed1998

Endometrial leucocytes: expression of steroid hormone receptors.

BACKGROUND: Stromal leucocyte populations in human endometrium comprise T cells, macrophages, and phenotypically unusual endometrial granulated lymphocytes. Their proportions vary during the menstrual cycle and, in particular, endometrial granulated lymphocytes increase in number in the late secretory phase. The stimulus responsible for these cyclical changes is unknown but it is likely that the steroid hormones oestrogen and progesterone play a role. AIMS: To define further the expression of steroid hormone receptors by leucocytes in non-pregnant and pregnant human endometrium. METHODS: Frozen and paraffin wax embedded sections of endometrium from non-pregnant women and early pregnancy decidua were labelled using single and double immunohistochemical techniques with monoclonal antibodies directed against oestrogen and progesterone receptors and various leucocyte subpopulations. RESULTS: Despite the prominence of CD56 positive endometrial granulated lymphocytes in late secretory phase endometrium and early pregnancy decidua, double immunohistochemical labelling showed no evidence of expression of either progesterone or oestrogen receptors by these cells or other endometrial leucocyte populations. CONCLUSIONS: Rather than acting directly, steroid hormones are likely to influence endometrial leucocyte populations indirectly via products of endometrial stromal or epithelial cells that express steroid hormone receptors.

Cryopreservation↗
PubMed1997

Cytotoxic activity of endometrial granulated lymphocytes during the menstrual cycle in humans.

CD56+ CD16- granulated lymphocytes, termed endometrial granulated lymphocytes (eGLs), have been suggested to play a role in the maintenance of human pregnancy, although their in vivo function in both pregnant and nonpregnant endometrium remains unknown. The present study compared the cytotoxic activity of CD56+ CD16- eGLs (> 98% purity) positively selected from early and late proliferative-phase, early and late secretory-phase, and menstrual-phase endometrium with that of CD56+ CD16- eGLs purified from first-trimester decidua and CD56+ predominantly CD16+ cells from peripheral blood. From the late proliferative phase onwards, the major histocompatibility complex (MHC)-nonrestricted cytotoxic activity of eGLs was comparable between phases of the menstrual cycle. In contrast, eGLs from early proliferative-phase endometrium displayed significantly lower cytotoxic activity. With the exception of eGLs purified from early proliferative-phase endometrium, the cytotoxic activity of CD56+ CD16- eGLs purified from nonpregnant endometrium was comparable to that of CD56+ CD16- eGLs in decidua and CD56+ predominantly CD16+ cells from peripheral blood. No endogenous lymphokine-activated killer cell activity was detected in eGLs from endometrium or decidua. The present study using highly purified eGLs demonstrates that, with the exception of early proliferative-phase samples, CD56+ CD16- eGLs from nonpregnant endometrium and early pregnancy decidua have cytotoxic activity comparable to that of "classical" natural killer cells from peripheral blood.

CD56 Antigen↗
PubMed1996

Immunohistochemical characterization of stromal leukocytes in ovarian endometriosis: comparison of eutopic and ectopic endometrium with normal endometrium.

OBJECTIVE: To compare stromal leukocyte subpopulations in different phases of the menstrual cycle in eutopic and ectopic endometrium from women with ovarian endometriosis and in control endometrium. DESIGN: Retrospective immunohistochemical study. SETTING: Department of Pathology, Royal Victoria Infirmary, Newcastle-upon-Tyne, United Kingdom. PATIENTS: Paraffin-embedded tissue blocks from 30 patients with endometriosis and 30 control blocks from patients undergoing hysterectomy for nonendometrial pathology were retrieved from archive files. MAIN OUTCOME MEASURE: Quantitative assessment of defined stromal leukocyte subpopulations in eutopic, ectopic and control endometrium at different stages of the menstrual cycle. RESULTS: In the proliferative and early secretory phases, ectopic endometrium contained elevated numbers of CD45+, CD3+, and CD43+ cells but reduced percentages of CD68+ macrophages. The proportions of granulated cells were reduced in ectopic endometrium throughout the cycle. No differences were noted between eutopic endometrium from women with endometriosis and control endometrium. CONCLUSION: Differences between eutopic and ectopic leukocyte subpopulations with the exception of large granular lymphocytes may be due to the lack of cyclicity demonstrated by endometriotic lesions.

Endometriosis↗
PubMed1996

Lectin histochemistry of rat placental tissues.

Lectin binding of rat trophoblast subpopulations was examined at days 10, 12 and 15 of gestation. Biotinylated lectins, specific for a range of carbohydrates, were applied to paraffin wax embedded tissues. At day 10 of pregnancy, a wide and similar range of lectins reacted with ectoplacental cone and giant cells: chorionic lamina was relatively unreactive except with wheat germ agglutinin. At days 12 and 15, the range of lectins reacting with the placental labyrinth was relatively restricted. Spongiotrophoblast at day 12 showed lectin reactivity similar to that of ectoplacental cone cells but at day 15 the reaction pattern indicated loss of N-acetylgalactosamine residues in the large, glycogen-rich cells. Trophoblastic giant cells also showed wide lectin reactivity: some reacted only with cytoplasmic components whilst others showed pericellular reactivity. Varying lectin reactivity of giant cells in different regions of the placenta suggests functional differences. There was reduced lectin reactivity of endovascular trophoblast at day 15, compared with day 12 of pregnancy, which may reflect altered invasive potential associated with loss of sialic acid and N-acetylgalactosamine residues. The pattern of lectin reactivity suggests that ectoplacental cells, as well as giving rise to giant cells, may also contribute to spongiotrophoblast and to endovascular trophoblast.

Animals↗
PubMed1996

Immunohistochemical evidence for increased numbers of 'classic' CD57+ natural killer cells in the endometrium of women suffering spontaneous early pregnancy loss.

Despite increasing knowledge about the cell populations that exist in the decidualized endometrium in normal early human pregnancy, little is known about the decidual leukocyte populations in women suffering spontaneous early pregnancy loss. Decidual leukocytes were investigated in 40 cases of spontaneous abortion using a panel of monoclonal antibodies specific for leukocytes, macrophages, T cells, B cells and 'classic' CD57(+) natural killer (NK) cells and an avidin-biotin peroxidase immunohistochemical technique. Endometrial granulated lymphocytes (eGL), the predominant decidual leukocyte population in the first trimester of normal human pregnancy, were demonstrated with the phloxine-tartrazine stain. There were significantly fewer leukocytes in decidua in spontaneous abortion, but the numbers of eGL, macrophages and T cells did not differ significantly between normal and pathological pregnancies. eGL and macrophages accounted for a greater proportion of the decidual leukocyte population in spontaneous abortion. Of the 40 spontaneous abortion cases, 20 had significantly increased numbers of 'classic' CD57(+) NK cells when compared with normal human pregnancy. A proportion of spontaneous abortions may occur because of increased 'classic' CD57(+) NK cell numbers in the decidua, which could become activated by local cytokines to attack the trophoblast.

Abortion, Spontaneous↗
PubMed1996

Quantitative analysis of T lymphocyte subsets in pregnant and nonpregnant human endometrium.

The purpose of this study was to characterize and quantify T lymphocyte populations and to investigate T cell antigen receptor (TcR) expression in human endometrium throughout the menstrual cycle and in early pregnancy. Frozen sections of endometrium were labeled using the highly sensitive avidinbiotin method and a panel of monoclonal antibodies. CD3-positive, CD8-positive, CD4-positive, TcR alpha beta-positive, and TcR gamma delta-positive cells were demonstrated in all phases of the menstrual cycle and in early pregnancy. There were no differences between pregnant and nonpregnant human endometrium in the proportion that each T cell subpopulation formed relative to the total CD3-positive T cell population. However, significantly fewer T cells were detected in early pregnant compared with nonpregnant endometrium. Our results clarify the TcR expression by T cells in pregnant and nonpregnant human endometrium and indicate that endometrial T cells are unlikely to play a significant role in implantation and the maintenance of human pregnancy since they decrease in number considerably in the first trimester of gestation.

Antibodies, Monoclonal↗
PubMed1996

Lectin histochemistry of pregnant rat uterine tissues.

Glycoconjugate residues were examined in the rat uterus at days 10, 12 and 15 of pregnancy using 17 biotinylated lectins with specificities for a variety of carbohydrate moieties. A wide variety of glycoconjugate residues were detected in the cytoplasm of some antimesometrial and mesometrial decidual cells with lectins from Canavalia ensiformis (Con A), Lens culinaris (LcH) culinaris (LcH), Pisum sativum (PSA), Griffonia simplicifolia II (GS-II), Triticum vulgaris (WGA), Griffonia simplicifolia I (GS-I), Maclura pomifera (MPA) and Phaseolus vulgaris (PHA-E and PHA-L). Reactivity with some of these lectins was also pericellular and the glycoconjugate residues detected may be related to extracelluar matrix produced by decidual cells. Reactivity with PHA-E, demonstrating complex carbohydrates, was most intense in the mesometrial decidua closest to the trophoblastic giant cells and may demonstrate glycoconjugates involved in maintaining integrity at this maternotrophoblast interface. Lectins derived from Helix pomatia (HPA), Vicia villosa (VVA), Glycine max (SBA) and Arachis hypogaea (PNA) reacted only with occasional small cells in antimesometrial or mesometrial decidua, probably demonstrating alpha and/ or beta-linked N-acetylgalactosamine residues on lymphocytes or monocytes. The glycoprotein granules of granulated metrial gland (GMG) cells in the decidua basalis and the metrial gland reacted strongly with WGA, MPA and PHA-L demonstrating complex carbohydrates including sialic acid residues and tri/tetra-antennary, nonbisected N-linked glycans. GMG cell cytoplasm reacted diffusely with Con A, LcH, PSA, WGA, PHA-E and PHA-L. In some GMG cells reactivity with WGA was apparently localised to the Golgi region indicating involvement in granule formation. Pericellular reactivity of some GMG cells with WGA may relate to migratory activity. The lectin reactivity of fibroblast-like stromal cells in the material gland was similar to that of the extracellular matrix and it is likely that many matrix molecules are produced by the stromal cells. A range of lectins (Con A, LcH, PSA, GS-II GS-I and PHA-L) reacted with some blood vessels in the metrial gland at day 12 of pregnancy: this may indicate activation changes associated with the transendothelial passage of GMG cells at this stage. Lectins derived from Dolichos biflorus (DBA), Bauhinia purpurea (BPA), Lotus tetragonolobus (LTA) and Ulex europaeus-I (UEA-I) did not react with decidual and metrial gland regions. Lectin binding profile studies can provide further information on the events occurring in the uterus in pregnancy: investigations at the ultrastructural level are required to resolve further intra and extracellular changes.

Animals↗
PubMed1995

Immunohistochemical characterization of cells retrieved by transcervical sampling in early pregnancy.

Trophoblastic cells can be retrieved from the endocervix and the lower uterine segment in early pregnancy by aspiration or lavage (Rodeck et al., 1995). The feasibility of using this technique for prenatal diagnosis depends on how frequently fetal cells can be retrieved and whether such cells can be purified from the predominant maternal cell population. In this study, specimens retrieved from the lower uterine segment prior to elective first-trimester termination of pregnancy were examined histologically and characterized using a panel of monoclonal antibodies in an avidin-biotin-peroxidase technique. Lavage samples generally contained fewer cervical epithelial cells than aspirates. Syncytial fragments or cytotrophoblast were identified in 9 of 12 lavage samples but in only 4 of 10 aspirates. Trophoblast cells were reactive with various anti-trophoblast monoclonal antibodies but the trophoblast cells present displayed considerable antigenic heterogeneity. For positive selection of trophoblast cells from these samples, it is likely that the best yield will be achieved by using a panel of carefully characterized monoclonal antibodies directed against various villous and extravillous trophoblast populations.

Antibodies, Monoclonal↗
PubMed1995

Beta 1 integrins in third trimester human placentae: no differential expression in pathological pregnancy.

Integrins are a group of cell surface receptors that play important roles in cell-cell and cell-extracellular matrix interactions. The expression of trophoblast cell surface integrin subunits changes during placental development in normal pregnancy but the functional significance is unknown. The aim of this study was to investigate the expression of beta 1 integrins and their extracellular matrix ligands in human placenta and membranes in normal and pathological pregnancy using an avidin-biotin-peroxidase technique. Expression of the beta 1 integrins was similar in all study groups. Whilst there was some heterogeneity of expression of specific integrin alpha chains this was not characteristic of defined subject groups, variations occurring within all groups. Two distinct trophoblast subpopulations were demonstrated in the chorion laeve according to differential expression of beta 1 integrins. Trophoblast immediately adjacent to maternal decidua, which expressed alpha 1 rather than alpha 2, also comprised the majority of trophoblast in the basal plate; possession of the alpha 1, alpha 3, alpha 5, alpha 6 rather than alpha 2, alpha 3, alpha 5, alpha 6 phenotype may be important in the invasive potential of trophoblast populations. The results obtained in the present study indicate that the integrin phenotypes of third trimester uteroplacental tissues are similar in normal and pathological pregnancy, including pre-eclampsia, before and after labour.

Extracellular Matrix↗