Polymyositis and ovarian carcinoma: a case report.

We are reporting a case of ovarian carcinoma, who presented with polymyositis. Polymyositis, without any evidence of dermatomyositis, as the presentation of ovarian carcinoma has never been reported. In fact, for patients with polymyositis, there does not appear to be a great increase in the risk of malignancy. The purpose of this report is to make the gynaecologists aware that polymyositis alone can also be the presenting symptom for ovarian carcinoma.

Alternatively spliced tenascin-C mRNA isoforms in human fetal membranes.

Tenascin-C is an extracellular matrix glycoprotein whose monomers include eight consecutive fibronectin type III-like repeats, encoded by exons 10-16, and which are subject to alternative splicing. Transcripts containing these exons are expressed during tissue wounding and active tissue remodelling. Human fetal membranes have been proposed to undergo active tissue remodelling as part of the mechanisms leading to their rupture and immunoreactive tenascin-C has been detected in this tissue. Employing reverse transcription-polymerase chain reaction (RT-PCR) and exon-specific primers, products corresponding to multiple splicing events in the alternatively spliced region have now been identified. The overall splicing pattern would indicate that the major transcripts correspond to complete exclusion of the alternatively spliced region; inclusion of only exon 16; and inclusion of exons 10-14 and 16, including or excluding exon 12. The sole site in tenascin-C susceptible to cleavage by matrix metalloproteinases (MMP)-2 and MMP-3 is found within the exon 12 encoded repeat, therefore translation of isoforms which include or exclude exon 12 may produce 'large' tenascins mediating functions ascribed to this form but susceptible or resistant to these MMPs. The demonstration of expression of 'large' tenascin mRNA isoforms supports the concept that fetal membranes at term are a site of active tissue remodelling.

Structural characteristics of term human fetal membranes prior to labour: identification of an area of altered morphology overlying the cervix.

Premature rupture of fetal membranes can have serious clinical implications, especially for the initiation of preterm labour and its consequences. To account for this phenomenon many studies have attempted to identify membrane features that may be uniquely associated with the site of rupture. Our previous work has identified an area of the fetal membrane, following spontaneous term birth which exhibits alterations consistent with structural weakness. The aim of this study was to determine if these changes existed prior to labour. In formalin-fixed paraffin-embedded tissue sections an area of the fetal membrane overlying the cervix, termed the 'cervical membranes', was characterized by an increased thickness of the connective tissue layer (215% increase, P < 0.01) and decreased thickness of both the cytotrophoblast (36% reduction, P < 0.01) and decidual layers (64% reduction, P < 0.01) compared to the rest of the membrane. This resulted in the cervical membranes being significantly thinner (P < 0.05) than the rest of the membrane. Similar changes were also detected in frozen sections of fetal membranes. These regional differences have two important implications in that: (i) the cervical membrane may represent a region of structural weakness susceptible to rupture during labour, and (ii) the paracrine relationships between fetal membranes and the myometrium may be qualitatively affected within different regions of the uterus.

Fetal fibronectin in cervicovaginal secretions as a predictor of preterm birth.

OBJECTIVE: To determine whether fetal fibronectin detected in cervicovaginal secretions of patients with symptoms suggestive of preterm labour is a predictor for preterm birth. DESIGN: A blind prospective observational study. SETTING: A teaching hospital. PARTICIPANTS: One hundred and forty-one women presenting to the delivery suite between 24 and 37 weeks of gestation (112 were between 24 and 34 weeks of gestation) with symptoms suggestive of preterm labour, with intact membranes and cervical dilation of < 2 cm. INTERVENTION: Specimens of cervicovaginal secretions were collected from the ectocervix and posterior fornix. Fetal fibronectin levels were measured by an ELISA and samples were considered positive if the level of fetal fibronectin present was > or = 0.05 microgram/ml. MAIN OUTCOME MEASURES: Gestation at birth and sampling-birth interval. RESULTS: The preterm birth (before 37 weeks of gestation) rate in the population studied was 19.1%. Fetal fibronectin predicted preterm birth with sensitivity of 63%, specificity of 95.6%, positive predictive value of 77.3%, and negative predictive value of 91.6%. Analysis of the data from women at less than 34 weeks of gestation showed similar results. A negative test accurately excluded (97.9%) the chance of subsequent birth during the three weeks interval following sampling. CONCLUSIONS: The presence of fetal fibronectin in the cervicovaginal secretions of women admitted with symptoms suggestive of preterm labour indicates a significant risk for subsequent preterm birth. The absence of fetal fibronectin in this group is a very strong indication that subsequent preterm birth is unlikely to occur. Fetal fibronectin test, if combined with clinical findings, has a potentially important role in clinical management of women with symptoms suggestive of preterm labour.

Differential expression of the integrin subunits in human fetal membranes.

The distribution of the alpha 1, alpha 3-alpha 6, beta 1, beta 3 and beta 4 integrin subunits in fetal membranes at term was examined using an indirect immunofluorescence technique and confocal laser scanning microscopy. In the amniotic epithelium, beta 4 integrin (alpha 6 beta 4) exhibited distinct basal localization, whereas beta 1 integrins (alpha 3 beta 1, alpha 5 beta 1) were localized basolaterally. This finding suggests that integrins, especially alpha 6 beta 4 which is a structural component of the hemidesmosomes, may function as basement membrane receptors. Integrins localized laterally may play a role in cell-cell interactions. beta 1 (alpha 1 beta 1, alpha 5 beta 1) integrins are probably involved in cell-matrix interactions in the connective tissue layers which are rich in collagens and fibronectin. Cytotrophoblasts, located predominantly towards the chorionic basement membrane, mainly expressed alpha 6 beta 4, while those located predominantly in the vicinity of decidua expressed alpha 5 beta 1, alpha 3 beta 1 and alpha 1 beta 1. Decidual cells expressed alpha 3 beta 1 and alpha 1 beta 1, whereas alpha 1, alpha 5, alpha 6, beta 1 and beta 4 were expressed in blood vessels. This pattern of integrin expression reflects the reported difference in composition of the extracellular matrix at these locations and obviates an important role for alpha 5 beta 1 at the chorio-decidual interface. The differential integrin expression at the cell-basement membrane interfaces demonstrated in this study (at amniotic epithelium, cytotrophoblasts, decidual cells and blood vessels) indicated a differential recognition of basement membranes by these cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Distribution of fibrillin-containing microfibrils and elastin in human fetal membranes: a novel molecular basis for membrane elasticity.

OBJECTIVES: The aim of this study was to determine the distribution of the elastic fiber components, elastin and the extensible fibrillin-containing microfibrils, in human fetal membranes, to understand the possible molecular basis of the membrane elasticity. STUDY DESIGN: Multiple fetal membrane specimens were obtained immediately after 10 normal vaginal deliveries at term. The distribution of elastin and fibrillin-containing microfibrils was studied by histochemical, immunohistochemical, immunofluorescence, and electron microscopic techniques. RESULTS: We failed to detect elastin in the fetal membranes with any of the applied techniques. However, fibrillin-containing microfibrils formed abundant longitudinal bundles that were primarily found in the fibroblast and reticular layers. The orientation of these bundles was parallel to direction of membrane stretch. They also formed bundles that extended from the amniotic, chorionic, and decidual basement membranes to the adjacent tissues. The fibrillin-containing microfibrils were also identified in the compact layer and in intercellular spaces of the trophoblasts but not in the spongy layer. CONCLUSIONS: We suggest that, in the absence of elastin, the structural organization and the extensibility of the fibrillin-containing microfibrils may represent a novel molecular basis for the elastic properties of the fetal membranes and contribute to their strength.

Structural characteristics of term human fetal membranes: a novel zone of extreme morphological alteration within the rupture site.

OBJECTIVE: To determine the structural characteristics of the rupture site of term fetal membranes (amniochorion and decidua) that rupture spontaneously after the onset of labour. DESIGN: Fourteen term fetal membranes were examined immediately after delivery at the light microscope level. Multiple samples were taken along the whole rupture site and long an axis between this site and placental edge. Morphometric analysis of the thickness of the constituent layers of the fetal membranes was performed. SETTING: Leicester Royal Infirmary Maternity Hospital. RESULTS: A restricted zone of extreme altered morphology, characterised by marked swelling and disruption of the connective tissue, thinning of the trophoblast layer and thinning or absence of decidua, was identified in the rupture site of all patients. Morphometric analysis of the thickness of membrane layers showed that these changes and the ratio between the thickness of the connective tissue layers and that of the trophoblast and decidua (termed fetal membrane morphometric index) were significant between the zone of extreme altered morphology and the rest of the membranes. CONCLUSIONS: The morphological features of the zone of extreme altered morphology suggests that it represents an area of structural weakness of the membranes. Since this zone did not include the whole length of the rupture site, it is likely that it was present before membrane rupture and was generated during pregnancy. We hypothesise that the zone of extreme altered morphology represents the site of initial rupture after which the tear is transmitted through the membranes to produce the rupture site. It is possible that if these changes become more extreme, then prelabour membrane rupture may occur. Further characterisation of this zone may help to understand the mechanism of its genesis and its role in predisposing the fetal membranes to rupture.

Confocal immunofluorescence localization of collagen types I, III, IV, V and VI and their ultrastructural organization in term human fetal membranes.

The distribution of collagen types I, III, IV, V and VI in term human fetal membranes was examined using conventional and confocal indirect immunofluorescence techniques. Collagens I and III were present in most of the layers of fetal membranes except in the trophoblast layer contrary to what has been previously reported. Although collagen IV is considered to be a basement membrane component our study, using monoclonal and polyclonal antibodies, showed its consistent presence in the spongy and reticular layers in high intensity. This was first report on the distribution of type V collagen in the chorion where it was found in the reticular and in the trophoblast layers. Type VI collagen was present mainly in the amnion and the reticular layer. The ultrastructural examination of the extracellular matrix showed that the main fibrous skeleton of the fetal membranes was formed of large banded fibres (Ultrastructurally identical to collagens types I and III) connected together and to the epithelial basement membranes by networks of unbanded filaments (collagen types V, VI and other components). The extensive and continuous networks formed by these collagens may be a major factor responsible for the mechanical integrity of the fetal membranes.