Bullous pemphigoid and ulcerative colitis: a report of two cases and description of immunoblot findings.
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Adult↗
Biomedical subjects
J D Aplin
Publications and source records attributed to J D Aplin.
Trophoblast differentiation during formation of anchoring villi in a model of the early human placenta in vitro.
In human implantation sites, formation of the cytotrophoblast shell and morphogenesis of anchoring villi occur during the 2nd and 3rd week of pregnancy. When placental villous tissue from 8-12 weeks was co-cultured with decidua parietalis, morphogenetic changes were observed specifically at sites of heterotypic contact, generating structures that closely resembled first trimester anchoring villi. Local breakdown of the syncytium and cytotrophoblast proliferation occurred, producing columns of cytotrophoblast. These columns showed complex changes of cell surface phenotype that replicate precisely the extravillous trophoblast differentiation pathway seen in vivo, including induction of integrin alpha 5 beta 1, loss of integrin alpha 6 beta 4 and expression of the HLA class I framework epitope recognized by monoclonal antibody W6/32. Extracellular matrix components including laminin, collagen type IV, fibrin and fibronectin were detected in intercytotrophoblastic spaces in the nascent columns. Spreading over the surface of the decidua and infiltration by cytotrophoblast were observed. We conclude that: (i) fist trimester floating villi retain the capacity to differentiate into anchoring villi; (ii) contact with decidua stimulates local breakthrough of the syncytium and cytotrophoblast proliferation; (iii) the resulting cytotrophoblast columns show phenotypic changes characteristic of these structures in vivo; and (iv) parietal decidua is capable of supporting implantation site-specific changes in a manner similar to the basal decidua.
Antigens, Surface↗
Molecular and Cellular Aspects of Peri-implantation Processes, Boston, Massachusetts 15-18 July 1994.
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Animals↗
MUC1, endometrium and embryo implantation.
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Cell Line↗
Cell adhesion molecules on the oocyte and preimplantation human embryo.
The presence of cell adhesion molecules on human oocytes, early embryos, and pre-hatched blastocysts was examined by indirect immunofluorescence and compared to the distribution found on first trimester villous placenta with the same antibodies. Six integrin subunits (alpha 3, alpha V, beta 1, beta 3, beta 4, beta 5) were observed consistently throughout preimplantation development. Evidence was also obtained for the presence of integrin subunits alpha 2, alpha 4, alpha L, beta 2, and beta 7 on a small number of oocytes. A more restricted developmental analysis of E-cadherin, ICAM-1, NCAM, and VCAM-1 demonstrated that these cell adhesion molecules are also present on oocytes and early embryos. L-selectin was detected on oocytes but was not found on 8-cell embryos. The oocyte and early blastomeres have complex surfaces in which the integrin and CAM families are represented.
Blastocyst↗
MUC1 in secretory phase endometrium: expression in precisely dated biopsies and flushings from normal and recurrent miscarriage patients.
MUC1 is a cell-surface and secretory product of endometrial epithelium. Immunohistochemical studies carried out using two different antibodies to the mucin-type tandem repeat region of MUC1 indicate a cell-surface location in proliferative phase glands, with intracellular deposits accumulating in the early secretory phase. Commencing 3-4 days after the luteinizing hormone (LH) peak and continuing into the late secretory phase, secretory MUC1 appears in gland lumens. Uterine flushings were collected as a function of time after the LH peak and were analysed using a two-site enzyme-linked immunosorbent assay for MUC1. Low but measurable concentrations were observed up to day 7, while on days 7-13 much higher values were obtained. In women suffering from recurrent spontaneous miscarriage, the concentration of MUC1 in flushings was significantly lower than in the controls on day LH + 10. Lower values were observed on days 7 and 13. Reduced epithelial secretory function and a resultant change in uterine fluid composition are features of endometrium from recurrent miscarriage patients.
Abortion, Habitual↗
CD44 is expressed throughout pre-implantation human embryo development.
The cell surface glycoprotein CD44 has been demonstrated in a variety of cell types in embryonic and adult tissues. We have established that CD44 is present on human oocytes, cumulus cells, early embryos and pre-hatched blastocysts by indirect immunofluorescence. We have also shown that CD44 is present on 8-11 week placental stroma cells, but not on the trophoblast. These findings demonstrate that CD44 is present throughout preimplantation development, and that down-regulation occurs on the embryonic surface after implantation.
Blastocyst↗
Studies of hemidesmosomes in human amnion: the use of a detergent extraction protocol for compositional and ultrastructural analysis and preparation of a hemidesmosome-enriched fraction from tissue.
A method is described for the sequential detergent and high ionic strength extraction of human amnion with the progressive enrichment of the intermediate filament (IF) cytoskeleton and its associated structures including hemidesmosomes (HD). TEM of the extracted epithelium in situ reveals IF bundles beneath the apical cell surface, around the nucleus and at the lateral edges of the cells where association with desmosomes occurs. IF bundles are also very prominent within basal cell processes where they loop through the cytoplasm adjacent to the HDs. A novel connecting filament network is observed running between the IFs and the hemidesmosomal dense plaque. The adjacent IF network contains both cytokeratin and vimentin, the latter revealed much more fully as a result of the extraction protocol. The hemidesmosomal plasma membrane contains integrin subunits alpha 6 and beta 4 and these are quantitatively retained as the basal cell surface during extraction, while nonjunctional plasma membrane is solubilised. Integrin beta 1 is found at the basolateral cell surface but, like actin, is extracted quantitatively and is not present in HDs. The extracted epithelial cells may be recovered by scraping and the IF network depolymerised to produce a particulate fraction containing short residual IFs, associated thin filaments and plaque material. This fraction contains immunoreactive cytokeratin and vimentin. Integrin alpha 6 beta 4 has been used as a biochemical criterion of the presence of HD material in the fraction. Both subunits are highly enriched. The fraction also contains the hemidesmosomal components HD1, BP230 and BP180. This method is likely to be useful in further characterisation of the HD.
Actins↗
Expression of type VI collagen mRNAs in human endometrium during the menstrual cycle and first trimester of pregnancy.
The pattern of type VI collagen deposition in human endometrium throughout the menstrual cycle and in decidua of the first trimester of pregnancy was studied. Immunohistochemical analysis demonstrated a dense microfibrillar network of collagen VI in the stroma of preimplantation endometrium which was reduced during the peri-implantation period and no longer detected in first trimester decidua. However, type VI collagen was consistently present within blood vessel walls in both endometrium and decidua. Using in situ hybridization, mRNAs encoding alpha 1(VI), alpha 2(VI) and alpha 3(VI) chains within endometrial stromal and vascular cells were identified. All three mRNA species are abundant in the villous mesenchyme of the first trimester placenta. The detection of collagen VI mRNA species in the endometrium throughout the menstrual cycle suggests that the apparent decrease in abundance of extracellular immunoreactive fibrils may be a consequence of translational control, matrix redistribution or turnover. In contrast, in the first trimester of pregnancy, collagen VI protein was mainly absent from the decidual stroma and amounts of mRNA were very low, indicating a significant reduction in production. Loss of stromal type VI collagen contributes to the remodelling of the maternal extracellular matrix of pregnancy.
Animals↗
The endometrial cell surface and implantation. Expression of the polymorphic mucin MUC-1 and adhesion molecules during the endometrial cycle.
The cell surface mucin MUC-1 is present in endometrial epithelial cells and their associated apical glycocalyx and is also released into gland lumens as a secretory product. MUC-1 mRNA and core protein are found at low levels in the proliferative phase of the cycle, but their abundance increases after ovulation. Endometrial MUC-1 has been found to carry sialokeratan sulphate chains and these show a dramatically increased abundance in cells and secretions in the post-ovulatory phase of the cycle, reaching a maximum in secretions 6-7 days after the LH peak. The apical epithelium also contains adhesion receptor molecules of the integrin and CD44 families. MUC-1 is large and highly glycosylated and probably extends farther from the cell surface than these 'conventional' glycoprotein receptors. It has the potential to inhibit sterically receptor-mediated cell-cell adhesion. However, it is also possible that MUC-1 displays specific (e.g., glycan) recognition structures for the initial attachment of the blastocyst or that the embryo may create a specialised microenvironment in which to implant.
Cell Adhesion Molecules↗
Brief communication: sliding displacement of amnion and chorion following controlled laser wounding suggests a mechanism for short-term sealing of ruptured membranes.
The Erbium-YAG laser was used to produce narrow wounds of defined depth in term amniochorion. The charring effect of the laser meant that sites could be readily localized in histological sections. During brief post-wounding incubations, sliding displacement of the amnion relative to the chorion occurred through the plane of the spongy layer. This suggests a possible short-term mechanism whereby a spontaneous rupture could be sealed in vivo.
Amnion↗
Endometrial responses to three different progestins in artificial cycles: a prospective, crossover study.
We found that there was no significant difference in endometrial responses to vaginal or IM P. But the response was suboptimal in cycles treated with dydrogesterone, suggesting that dydrogesterone treatment is not the preferred progestin for use in artificial cycles.
Administration, Intravaginal↗
Endometrial differentiation in the peri-implantation phase of women with recurrent miscarriage: a morphological and immunohistochemical study.
OBJECTIVES: To study endometrial differentiation in the peri-implantation phase of women with recurrent miscarriage and to compare the results with endometrium of normal fertile women. DESIGN: A prospective study of endometrial specimens precisely timed from the LH surge, using traditional histologic dating (Noyes' criteria), quantitative histologic measurement (morphometric analysis), and immunohistochemical techniques. RESULTS: Fifteen of 25 (60%) subjects in the recurrent miscarriage group had retarded endometrial development in the peri-implantation period as monitored by morphometry. The recurrent miscarriage group showed reduced levels of four mucin-related secretory epitopes, and greater reductions were associated with morphological retardation. Normal differentiation was observed in all of the 14 subjects in the control group. CONCLUSIONS: Women with idiopathic recurrent pregnancy loss may be divided into two distinct subgroups on the basis of their endometrial response in the peri-implantation period. Precisely timed endometrial biopsy should be incorporated in the investigation of recurrent miscarriage.
Abortion, Habitual↗
Keratan sulphate as a secretory product of human endometrium: cyclic expression in normal women.
The distribution of keratan sulphate (KS) in normal endometrium has been studied by immunohistochemistry using monoclonal antibody 5D4. KS is present in association with glandular epithelium throughout the normal cycle. Production is hormonally regulated, as indicated by the significant increase observed in the secretory phase of the cycle. Intracellular immunoreactivity increases to a maximum 3 days after the luteinizing hormone (LH) peak. This is followed by an increase in secreted KS from 4 days after the LH peak, and essentially all endometrial glands showed immunoreactive deposits by 5 days after the LH peak. Beginning on day 7 after the LH peak, a fraction of glands was observed to have lost the epitope. Nevertheless, KS remained in a significant proportion of the gland lumens 9 days after the LH peak. The data suggest that analysis of secretory KS in women gives an index of hormonally regulated epithelial differentiation in the peri-implantation phase.
Adolescent↗
Expression of two isoforms of CD44 in human endometrium.
The distribution of the cell-surface adhesion glycoprotein CD44 in human endometrium was examined by immunofluorescence using six monoclonal antibodies to epitopes common to all forms of the molecule, and by reverse transcription-polymerase chain reaction (RT-PCR). Immunoreactivity was observed throughout the menstrual cycle in stroma, vessels, glandular, and luminal epithelium. Variations in staining intensity were observed, especially in the epithelial compartment. CD44 was also expressed strongly by decidualized stromal cells of first-trimester pregnancy. No systematic variation of immunoreactivity was observed with stages of the normal cycle, but a fraction (25%) of the specimens lacked reactivity in the epithelium. To determine the molecular size of the epithelial isoform, an immunoprecipitation technique was developed using surface-radioiodinated, detergent-extracted glands. This indicated the presence at the cell surface of a single dominant CD44E species with an approximate molecular mass of 130 kDa. RT-PCR was used to investigate the isoforms present in whole endometrial tissue, isolated gland fragments, and Ishikawa endometrial carcinoma cells. Complementary DNA produced from total endometrial mRNA was PCR-amplified across the splice junction between exons 5 and 15. Transcripts corresponding to the hyaluronate receptor CD44H as well as a larger isoform were identified. CD44H was absent, or very scarce, in cDNA from purified gland epithelium. In contrast, Ishikawa cells expressed this form abundantly. The glands and Ishikawa cells also expressed CD44E containing sequences encoded by exons 12, 13, and 14. These data demonstrate the presence of CD44 in human endometrium and decidua, and show that different isoforms of CD44 are associated with tissue compartments in which different functional roles can be anticipated.
Base Sequence↗
Antigenic expression of integrin alpha 6 beta 4 in junctional epidermolysis bullosa.
Integrin alpha 6 beta 4 is a major component of hemidesmosomes, considered to play a central role in the adhesion of basal epidermal cells to the underlying dermis. It is therefore of considerable interest in the study of the aetiology of inherited blistering disorders. We have examined the immunohistochemical characteristics of skin from 16 patients with epidermolysis bullosa using two antibodies directed against epitopes on the beta 4 subunit of alpha beta 4 integrin (G71, 3E1), one antibody directed against an epitope on the alpha 6 subunit (GoH3), GB3 an antibody for nicein, and LH7.2, an anticollagen type VII antibody. All 10 patients with junctional epidermolysis bullosa showed markedly reduced or no immunoreactivity with G71. These patients included two with GB3-positive junctional epidermolysis bullosa associated with pyloric atresia, and four with other subtypes. By contrast, five patients with dystrophic epidermolysis bullosa and one patient with epidermolysis bullosa simplex showed normal immunoreactivity with G71. In this study, G71 is shown to have a high specificity and sensitivity for the diagnosis of junctional epidermolysis bullosa. Immunoreactivity with 3E1 and GoH3 was normal in most patients, consistent with published reports showing normal immunoreactivity with other beta 4 and alpha 6 subunit antibodies. The data suggest a modification of the beta 4 subunit of integrin alpha 6 beta 4 at the dermo-epidermal junction in junctional epidermolysis bullosa.
Antibodies↗
The polymorphic epithelial mucin MUC1 in human endometrium is regulated with maximal expression in the implantation phase.
After ovulation, progesterone stimulates a temporally regulated secretory transformation in human endometrial epithelium. Using a combination of immunohistochemistry, and Western and Northern blotting, we demonstrate that 1) the polymorphic epithelial mucin MUC1 is secreted by human endometrial epithelium; 2) low levels of both mRNA and core protein are present in the preovulatory phase of the menstrual cycle; 3) mRNA levels increase several-fold after ovulation, consistent with transcriptional regulation by progesterone; 4) there is an increase in translation product in postovulatory endometrium; and 5) the tandem repeat domain of the MUC-1 polypeptide is glycosylated in endometrium.
Antibodies, Monoclonal↗
Comment: effect of cytokines on prolactin production by human decidual stromal cells in culture: studies using cells freed of bone marrow-derived contaminants.
Human decidua contains resident decidual cells alongside a population of bone marrow-derived cells, among which macrophages and large granular lymphocytes are most abundant. We hypothesized that soluble effectors produced by bone marrow-derived cells may modulate the function of the decidual cells. To investigate this, a cell purification protocol was devised that involved digestion of first-trimester decidua with collagenase and hyaluronidase to produce a mixed stromal cell suspension from which the bone marrow-derived cells were removed using immunomagnetic beads coated with anti-CD45. The resulting stromal cells were maintained in culture in the presence of progesterone and were found to produce PRL. The effect of a panel of cytokines on PRL production was examined. Tumor necrosis factors-alpha and -beta had a dose-dependent inhibitory effect, and tumor necrosis factor receptors were identified on the cells. Interleukin 1 alpha and 1 beta, platelet-derived growth factor, and transforming growth factor-beta 1 were also found to inhibit PRL production, and platelet-derived growth factor and transforming growth factor-beta 1 stimulated cell proliferation. These findings suggest an interaction between the immune and endocrine systems in regulating the maternal environment of early pregnancy.
Bone Marrow Cells↗