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Biomedical subjects

J N Bulmer

Publications and source records attributed to J N Bulmer.

At least 127 records · Page 7Linked to original sources

Absorption of lignocaine through split-skin donor sites.

Seventeen patients undergoing split-skin grafting each received 3 mg/kg of a sterile 1% lignocaine gel applied to an area of the donor site equal to 3 sq cm/kg. Serial venous blood samples were taken for one hour following application and analysed for serum lignocaine concentration by high pressure liquid chromatography. The concentrations in all the patients were well below those associated with systemic toxicity. Clinical assessment included haemodynamic monitoring during the procedure, and postoperative evaluation of possible central nervous effects and of the degree of donor site analgesia obtained. No untoward effects were noted and the degree of analgesia, although difficult to assess, appeared good.

Administration, Topical↗

Immunohistological characterization of the decidual leucocytic infiltrate related to endometrial gland epithelium in early human pregnancy.

The leucocytic infiltrate which is associated with maternal endometrial glands in decidual tissue in early human pregnancy has been shown by immunohistology to consist mainly of macrophages and T lymphocytes. Cells expressing HLA-DR were prominent around the glands, and most were also reactive for the Leu-M3 tissue macrophage antigen. In addition, HLA-DR-positive T cells were identified by double immunoenzymatic labelling, situated both immediately adjacent to the gland epithelium and in adjacent aggregates. Some accumulation of HLA-DR-positive cells has also been noted around the glands in non-pregnant endometrium during the mid and late secretory phases, and occasional T6 antigen-bearing cells were also detected. Occasional HLA-DR-positive surface and gland epithelial cells were observed in both pregnant and non-pregnant specimens. These results indicate that, in early human pregnancy, the endometrial glands may be subject to a form of active immune response partially under hormonal control.

Cell Movement↗

Immunohistologic identification of trophoblast populations in early human pregnancy with the use of monoclonal antibodies.

Three murine monoclonal antibodies (H315, H316, and NDOG1) have been used in a peroxidase-antiperoxidase technique on formalin-fixed paraffin-embedded tissues to identify populations of fetal trophoblast cells by their expression of membrane antigens in chorionic and decidual tissue from the first trimester of normal human pregnancy. H315 and H316 showed comparable staining of placental villous syncytiotrophoblast and cytotrophoblast and were also able to distinguish subpopulations of nonvillous trophoblast in the placental bed, including perivascular and endovascular trophoblastic cells as well as cytotrophoblastic elements within the decidua and myometrium. H315 and H316 also showed cytoplasmic staining of columnar epithelium of endometrial glands throughout the first trimester. In contrast, NDOG1 stained chorionic syncytiotrophoblast but not villous cytotrophoblast and also did not react with any cytotrophoblastic elements in the placental bed. NDOG1 distinguished these different subpopulations of trophoblast as early as 13 to 15 days after ovulation.

Animals↗

Immunohistological characterization of lymphoid cell populations in the early human placental bed.

The distribution of leukocytes in first trimester human decidual tissue has been studied by using a panel of monoclonal antibodies in an indirect immunoperoxidase technique on acetone-fixed cryostat sections. The results indicate that bone marrow-derived cells are abundant in the placental bed and a proportion of these are HLA-DR positive. However, a major leukocyte population in the decidua of early pregnancy is of cells which carry the E-rosette receptor but which do not express peripheral pan-T cell antigens nor HLA-DR. The distribution of these cells suggests that they are endometrial granulocytes. A similar large number of cells express OKT 10, a marker of immature or activated cells. The presence of this unusual T lineage cell raises the possibility that a form of lymphocyte processing is occurring in the decidua in early pregnancy, perhaps in response to foetal antigens presented on trophoblast.

Antibodies, Monoclonal↗

Macrophage populations in the human placenta and amniochorion.

Fetal and maternal macrophage populations in human utero-placental tissues at different stages of gestation have been studied using immunohistological and histochemical techniques. A large population of macrophages has been identified within maternal decidualized endometrium in both term and first trimester tissues, although lymphoid cells also constitute a major component of the bone marrow derived cells in the decidua of early pregnancy. In contrast, fetal macrophages have been shown to contribute nearly all of the substantial bone marrow derived cell population within placental chorionic villous mesenchyme and within the mesenchyme of the term amniochorion. Apart from a small population of stellate intensely HLA-DR positive cells in term placental villous stroma, these extra-embryonic fetal macrophages could be shown consistently to express both the leu-M3 tissue macrophage antigen and lysosomal enzyme activities. It is suggested that the major HLA-DR positive cell population of fetal amniochorion comprises 'classical' macrophages rather than dendritic type cells. These various macrophage populations may perform vital phagocytic and degradative functions within utero-placental tissues and amniochorion.

Amnion↗

Bone-marrow origin of endometrial granulocytes in the early human placental bed.

A large number of cells in the first trimester human placenta have been shown to express leucocyte-common antigen by the use of a monoclonal antibody in an immunoperoxidase technique. The distribution of endometrial granulocytes in the decidua of early pregnancy indicates that a large proportion of these cells bear the leucocyte-common antigen and are thus bone-marrow derived.

Antibodies, Monoclonal↗

Peroxidase-labelled lectin binding of human extravillous trophoblast.

The binding of four peroxidase-conjugated lectins, concanavalin A (Con-A), wheat germ agglutinin (WGA), peanut agglutinin (PNA) and soybean agglutinin (SBA), in both fixed and frozen tissue sections of human extravillous trophoblast (EVT) was determined. On the basis of its lectin binding properties the EVT cell population was found to be heterogeneous. PNA and SBA did not bind to any of the EVT cells. Con-A and WGA bound to most EVT cells, with the exception of the trophoblast of the chorion laeve. The trophoblast giant cells bound only Con-A and not WGA. The villous cytotrophoblast, from which the EVT cells are said to derive, does not express the sugar groups detected by the above lectin probes. The expression of mannosylated and di-N-acetylchitobiosyl residues by a fetally derived cell invites speculation that such expression enables it both to invade host maternal tissues and to avoid any adverse host immunological response.

Arachis↗

Placenta accreta: an immunohistological study of trophoblast populations.

Trophoblast populations in four cases of placenta accreta were characterized using antibodies directed against cell membrane antigens, placental hormonal products and low-molecular-weight cytokeratins in standard immunoperoxidase techniques. The results obtained with antibody to syncytiotrophoblast membrane (rabbit anti-StMPM), antibody to an epithelial membrane antigen (HMFGI) and a cytokeratin marker (CAM 5.2) appeared identical to those reported for normal term placental tissues. Similarly the localization of human placental lactogen (hPL), human chorionic gonadotrophin (hCG) and pregnancy-specific beta 1-glycoprotein (SP1) within trophoblast populations in placenta accreta was identical to their reported distribution in term placenta. However, increased reactivity at the villous-maternal junction was demonstrated with NDOGI, an antibody raised against term syncytiotrophoblast membrane and directed against hyaluronic acid. NDOGI reactivity at this site is normally maximal during early placental development and is virtually absent in the third trimester. The results suggest that placenta accreta does not arise through excessive trophoblast invasiveness or proliferation and the absence of decidua is of more importance in the pathogenesis. Trophoblast may regulate its development at an unfavourable intramyometrial implantation site by the production of hyaluronic acid.

Antigens, Surface↗

Immunohistochemical studies of fetal trophoblast and maternal decidua in hydatidiform mole and choriocarcinoma.

Immunohistochemical techniques have been used to investigate the expression of fetal trophoblast antigens and the maternal leucocytic response in molar pregnancy and choriocarcinoma. The antigenic phenotype of morphologically defined trophoblast populations in complete, partial and invasive moles was analogous to that in normal pregnancy. All trophoblast phenotypes described in normal pregnancy were also identified in choriocarcinoma, suggesting that extensive differentiation into heterogeneous subgroups occurs in malignant trophoblast. The maternal leucocytic infiltrate in molar pregnancy consisted of T lymphocytes and class II MHC-positive macrophages. CD2-positive, CD3-negative lymphocytes were identified in molar decidua but not in uterine tissue in choriocarcinoma. Similarly, endometrial granulocytes were present in molar decidua but not in choriocarcinoma; these cells were associated with decidualization rather than with fetal trophoblast.

Choriocarcinoma↗

Maternal and fetal cellular relationships in the human placental basal plate.

Maternal and fetal cellular relationships in the normal human term placental basal plate were investigated by single and double immunohistochemical labelling techniques. Extravillous fetal trophoblast in the basal plate was uniformly reactive with markers of low-molecular-weight cytokeratins. The predominant maternal leucocyte population in the basal plate consisted of leucocyte-common-antigen-positive, class II MHC-positive macrophages, which exhibited acid phosphatase activity. Double-labelling methods highlighted the close association of these macrophages with extravillous trophoblast: they often extended processes around the fetal cells and were also observed within islands of cytotrophoblast. Other leucocytes were uncommon, although aggregates of T cells were apparent in some tissues.

Antibodies, Monoclonal↗

Fibronectin and laminin in the early human placenta.

The distribution of fibronectin and laminin was investigated in early intrauterine and ectopic tubal pregnancy using a standard immunoperoxidase technique on paraffin-embedded tissues. Localization of both fibronectin and laminin appeared identical in intrauterine and in ectopic pregnancy. Fibronectin was demonstrated in chorionic villous stroma, in the distal cytotrophoblast cell columns, in infiltrating mononuclear extravillous trophoblast and in endovascular trophoblast. Villous trophoblast and multinucleate interstitial trophoblast did not label. Extracellular fibronectin was demonstrated amidst sheets of infiltrating extravillous trophoblast. Laminin distribution was similar to that described for fibronectin but laminin was also present in the basement membrane of villous cytotrophoblast. Both fibronectin and laminin showed a pericellular distribution around decidual stromal cells. This study demonstrates further heterogeneity of human trophoblast populations. The presence of fibronectin in infiltrating extravillous trophoblast, endovascular trophoblast and in the distal columns may enhance trophoblast adhesion to maternal tissues and facilitate trophoblast migration.

Chorionic Villi↗

Monoclonal antibodies to T cell receptor gamma/delta complex react with human endometrial glandular epithelium.

We have tested a panel of four monoclonal antibodies to the T cell receptor (TCR) gamma/delta heterodimer (delta TCS-1, TS-8, TCR delta-1, anti- C gamma m 1) in pregnant and non-pregnant uteri. The TCR gamma/delta complex was not detected on stromal lymphocytes, but was localized in the cytoplasm of the endometrial glandular epithelium from most pregnant uteri. These antibodies also reacted with endometrial glandular epithelium in a majority of non-pregnant uteri; the reactivity was more consistent in secretory phase glands than that in the proliferative phase of menstrual cycle. However, three different monoclonal antibodies to CD3 (OKT3, leu 4, UCHT-1) failed to show any reactivity, suggesting that the presence of the TCR gamma/delta complex was not associated with CD3 complex. The TCR gamma/delta-positive glandular epithelial cells did not react with two monoclonal antibodies to the TCR alpha/beta complex, and they were also CD4- and CD8-negative. Together with the loss of the class 1 MHC antigens from these endometrial glandular epithelial cells in early pregnancy, these data suggest that these TCR gamma/delta-bearing endometrial glandular cells may undergo phenotypic alterations under local regulation of gene expression.

Antigens, CD↗

Antigen expression by trophoblast populations in the human placenta and their possible immunobiological relevance.

Antigen expression by villous and extravillous human trophoblast populations at discrete anatomical sites has been reviewed. The various different antigenic phenotypes have been highlighted using a panel of monoclonal antibodies reactive with characteristic trophoblast membrane antigens, a trophoblast-leucocyte common antigen, class I MHC antigens, epithelial cell cytokeratin and epithelial membrane markers. This approach has allowed three separate fetal trophoblast populations to be identified within term amniochorionic membranes, and also has facilitated further definition of trophoblast populations in maternal uterine tissues. Furthermore, antigenic alterations have been noted in the maternal uterine gland epithelium in pregnancy leading to the expression of a trophoblastic phenotype, thereby suggesting a mechanism of extrinsic regulation of gene expression in these tissues. The possible involvement in the immunoregulatory control of maternal responses in pregnancy of MHC-linked gene products expressed by trophoblast has been discussed.

Antibodies, Monoclonal↗

Phenotypic and functional studies of leukocytes in human endometrium and endometriosis.

The aetiology of endometriosis, a common and disabling disorder, is presently unknown, although immune dysfunction could allow ectopic endometrial fragments to survive outside the uterine cavity. These studies investigate the relationship between leukocyte populations, steroid hormone receptor expression, proliferative activity, bcl-2 expression and apoptosis in eutopic and ectopic endometrium from women with endometriosis or adenomyosis at different phases of the menstrual cycle. Significantly increased oestrogen receptor expression, bcl-2 expression and numbers of CD8+ leukocytes were found in ectopic compared with eutopic endometrium in endometriosis, and CD56+ endometrial granulated lymphocytes (eGLs) were significantly reduced in ectopic endometrium. Apoptotic cells were rarely found in control and subject endometria. In contrast with endometriosis, adenomyotic lesions showed identical steroid hormone receptor expression, proliferative activity, bcl-2 expression and leukocyte subpopulations to eutopic endometrium, indicating different aetiologies for these disorders. The unusual CD56+ CD16- eGLs present in large numbers in late secretory phase eutopic endometrium were highly purified (>98%) by immunomagnetic separation. Except for a negligible cytotoxic activity of eGLs from early proliferative samples, cytotoxic activity of eGLs from non-pregnant endometrium during the menstrual cycle was comparable with those in peripheral blood, predominantly CD56+ CD16+ natural killer cells. eGLs from non-pregnant endometrium and early pregnancy showed a variable proliferative response to 5 and 100 U/ml interleukin-2 over 48-h and 120-h time courses. eGLs are evidently functionally important in the eutopic endometrium. Their absence in endometriotic lesions together with increased CD+8 T-cell numbers and increased oestrogen receptor and bcl-2 expression may have significant effects on the development and progression of endometriosis.

Antigens, CD↗

Expression of epidermal growth factor receptor and transferrin receptor by human trophoblast populations.

Epidermal growth factor (EGF) has several roles, including stimulation of cell division and differentiation. EGF receptor (EGFR) has been localized to villous syncytiotrophoblast, but expression by other human trophoblast populations has not been reported. EGFR expression was examined in normal and pathological placental tissues using a streptavidin-biotin-peroxidase technique; results were compared with expression of transferrin receptor (Tf-R) in similar tissues. EGFR was detected on villous syncytiotrophoblast in early and term pregnancy with labelling of the apical membrane, focal cytoplasmic reactivity, and patchy labelling of the trophoblast basement membrane. In contrast with other reports, EGFR was also consistently localized to villous cytotrophoblast, chorion laeve, and extravillous trophoblast populations in maternal uterine tissues. Maternal decidua showed diffuse labelling of stromal cells, particularly in the superficial zones. The reaction pattern in ectopic tubal pregnancy was similar to that in early intrauterine pregnancy. In molar pregnancy, EGFR was detected on villous syncytiotrophoblast and cytotrophoblast. In contrast, in normal, ectopic, and molar pregnancies labelling for Tf-R was confined to syncytiotrophoblast and to the proximal portions of the cytotrophoblast columns. Expression of EGFR by all trophoblast cells may represent a mechanism of placental growth and proliferation control. EGFR may also be involved with establishment of differentiated trophoblast functions including hormone secretion.

Antibodies, Monoclonal↗