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Ultrastructural and immunohistochemical studies of stromal cells in lamina propria of human fallopian tube ampullar mucosa: the recognition of 'CD34 positive reticular network' and its putative function for immune surveillance.

This paper aims at clarifying the cellular differentiation at the ultrastructural and immunohistochemical levels in normal stromal cells of the fallopian tube ampullar mucosa in order to arrive at a functional interpretation of these cells. Techniques used were histology, histochemistry, transmission and scanning electron microscopy, as well as light and ultrastructural immunohistochemistry for the CD34 antigen. Three types of stromal mesenchymal cell were identified. The most frequent cell-type had a fibroblastic shape and lacked the lamina and myofilaments typical of smooth-muscle. It was, however, positive for alpha-smooth-muscle actin (alpha-SMA). It was negative for desmin (D), but positive for the CD34 antigen. This cell was therefore rather undifferentiated ultrastructurally but had a partial smooth-muscle immunophenotype: it was designated as an ultrastructurally undifferentiated smooth-muscle cell (U-SM cell). A second category consisted of overt smooth-muscle cells (SM cells): they were rich in myofilaments, had a lamina and were D(+) and alpha-SMA(+). The third category resembled SM cells but were D(-): these were designated D(-) SM cells. U-SM cells, SM cells and D(-)SM cells accounted for 83%, 13% and 4% of the total stromal cell population respectively. U-SM cells had lipid-rich residual bodies, solitary cilia, simple intercellular and cell-to-matrix junction, and they were frequently adherent to mononuclear cells. This phenotype was present irrespective of the varied clinical picture of the patients from whom samples were obtained. The observations suggest that the stroma of the fallopian tube ampullar mucosa consists of a reticulum composed largely of CD34(+) U-SM cells in combination with mononuclear cells. One of the main roles suggested for this CD34 positive reticular network is immune surveillance.

Acid Phosphatase↗

Influence of microsurgical reanastomosis of the fallopian tube on luminal pH and PO2 and on the fertilization rate and embryo development in the rabbit oviduct.

The luminal pH and PO2 were measured in rabbit oviducts to evaluate the influence of microsurgery on the environment within the fallopian tube before and after resection of a 1 cm ampullary portion with subsequent tubal reanastomosis. While the oxygen tension showed no difference between the operated oviduct (56 +/- 16 mmHg, n = 8) and the control side (53 +/- 13 mmHg, n = 8), there was a significant pH decrease in the oviducts after microsurgery (7.94 +/- 0.10, n = 8, versus 7.75 +/- 0.16, n = 8, p less than 0.0025). In the second part of the experiment the operated animals were induced to ovulate by hCG injection, and artificial insemination was performed at the same time. The number of fertilized and unfertilized oocytes and the stages of embryonic development (64 h post hCG) were compared between the operated and control oviducts. From the operated oviducts a lower number of ova were recovered and a lower rate of fertilization was observed. The data indicate that microsurgery of the rabbit fallopian tube does not disturb the luminal oxygen tension but may cause a lower pH. Ultimately a reduced rate of fertilization and impaired early development were observed.

Animals↗

A candidate precursor to serous carcinoma that originates in the distal fallopian tube.

The tubal fimbria is a common site of origin for early (tubal intraepithelial carcinoma or TIC) serous carcinomas in women with familial BRCA1 or 2 mutations (BRCA+). Somatic p53 tumour suppressor gene mutations in these tumours suggest a pathogenesis involving DNA damage, p53 mutation, and progressive loss of cell cycle control. We recently identified foci of strong p53 immunostaining-termed 'p53 signatures'-in benign tubal mucosa from BRCA+ women. To examine the relationship between p53 signatures and TIC, we compared location (fimbria vs ampulla), cell type (ciliated vs secretory), evidence of DNA damage, and p53 mutation status between the two entities. p53 signatures were equally common in non-neoplastic tubes from BRCA+ women and controls, but more frequently present (53%) and multifocal (67%) in fallopian tubes also containing TIC. Like prior studies of TIC, p53 signatures predominated in the fimbriae (80-100%) and targeted secretory cells (HMFG2 + /p73-), with evidence of DNA damage by co-localization of gamma-H2AX. Laser-capture microdissected and polymerase chain reaction-amplified DNA revealed reproducible p53 mutations in eight of 14 fully-analysed p53 signatures and all of the 12 TICs; TICs and their associated ovarian carcinomas shared identical mutations. In one case, a contiguous p53 signature and TIC shared the same mutation. Morphological intermediates between the two, with p53 mutations and moderate proliferative activity, were also seen. This is the first report of an early and distinct alteration in non-neoplastic upper genital tract mucosa that fulfils many requirements for a precursor to pelvic serous cancer. The p53 signature and its malignant counterpart (TIC) underline the significance of the fimbria, both as a candidate site for serous carcinogenesis and as a target for future research on the early detection and prevention of this disease.

Biomarkers, Tumor↗

Mucosal epithelial proliferation of the fallopian tube: prevalence, clinical associations, and optimal strategy for histopathologic assessment.

The prevalence and clinical significance of mucosal epithelial proliferation or hyperplasia of the fallopian tube are controversial in the few studies reported. Some authors have retrospectively examined "routine" sections (one or two submitted from each tube), whereas others have prospectively blocked the entire tubes. In the current study, we prospectively studied a total of 168 tubes from 98 women who had various indications for salpingectomy and compared the diagnosis in an initial single section (to simulate the usual practice) with that in the remainder of the entirely sectioned and submitted tube (mean total number of sections, 9.0). Some degree of mucosal epithelial proliferation was found in 83% of all tubes examined, with no difference between the tubes removed for routine tubal ligation and those in women who had benign ovarian lesions, malignant gynecologic tumors, uterine leiomyomata, or benign tubal lesions (salpingitis or ectopic pregnancy). Mucosal epithelial proliferation graded as more than mild, however, was seen in only 4.5% of the otherwise normal ligated tubes versus 35 to 46% of tubes associated with the other lesions. When the initial sections were compared with the subsequent ones, the diagnosis was identical in 96 tubes (57%). In the other 72 tubes (43%), the difference in diagnosis was never greater than one grade (no, mild, moderate, severe mucosal epithelial proliferation), with the diagnosis more often upgraded (50 tubes) than downgraded (22 tubes) in the additional sections. It is concluded that there is no reason to submit an entire tube for histologic examination to detect clinically significant lesions, and the usual practice of submission of one or two sections is clinically appropriate.

Cell Division↗

Opa (protein II) influences gonococcal organization in colonies, surface appearance, size and attachment to human fallopian tube tissues.

Opa-expressing variants of Neisseria gonorrhoeae strain F62-SF and an Opa- variant, all non-piliated, were examined for differences in the interaction of the bacteria within colonies and in attachment to and damage of human fallopian tube mucosa. Expression of certain Opas was associated with the formation of transparent colonies where the bacteria were tightly packed and evenly spaced within the colonies. Expression of other Opas was associated with the formation of opaque colonies where the gonococci were less tightly packed and were unevenly spaced. Distinct differences in the size of the gonococci and in their surface characteristics were dependent upon the Opa being expressed. Certain Opas were associated with gonococci that had significantly larger cross-sectional areas and bigger perimeters. Scanning electron microscopy showed that OpaC- and OpaD-containing variants yielded greater mucosal damage than OpaB-containing and Opa- variants with the least damage caused by the OpaA-containing variant (clumped bacteria from dark opaque friable colonies). The mucosal damage after 60 min incubation included shortening and decreased numbers of microvilli on non-ciliated cells and invagination and sloughing of ciliated cells. Differences in the interactions of gonococci within colonies and in attachment to fallopian tube mucosa and damage to the mucosal cells occurred with different Opa-expressing variants of N. gonorrhoeae strain F62-SF.

Antigens, Bacterial↗

Preoperative serum hCGbeta as a prognostic marker in primary fallopian tube carcinoma.

OBJECTIVES: It was the aim of this study to evaluate the prognostic value of the pretreatment serum concentrations of the beta-subunit of human chorionic gonadotropin (hCGbeta), CA 125 and tumour-associated trypsin inhibitor (TATI) in primary fallopian tube carcinoma (PFTC). METHODS: The pretreatment serum concentrations of hCGbeta, CA 125 and TATI were analyzed in serum samples from 60 women with a mean age of 61 years, treated for PFTC between 1985 and 2000. Of the 91 patients treated during this period, 31 were excluded because no serum sample was available. The patients were followed-up for recurrence and survival until February 14, 2003. The prognostic value of the serum markers were compared with those of stage, grade and histological type. RESULTS: The median survival time was 27 months and the overall 5-year survival rate 33%. Stage and size of the residual tumour (<1 vs. > or =1 cm) predicted both overall and disease-free survival (p < 0.050). Histology (serous vs. others) (p = 0.023) also influenced overall survival. Overall 5-year survival was 38% when serum hCGbeta was below 3.5 pmol/l, while it was 18% when the level was higher (p = 0.052). The corresponding disease-free 5-year survival was 38 and 20%, respectively (p = 0.014). Patients with CA 125 values above 1,017 kU/l had an overall 5-year survival of 39% as compared with 14% for those with lower values (p = 0.009), while the disease-free survival was 37 and 23%, respectively (p = 0.096). Serum TATI was not a prognostic marker. Serum concentrations of hCGbeta and CA 125 correlated significantly with stage (p = 0.049 and p = 0.050, respectively). In multivariate Cox proportional hazards regression analysis, only hCGbeta, stage and histology emerged as independent prognostic factors. CONCLUSIONS: Clearly elevated serum concentrations of hCGbeta and CA 125 predict survival in fallopian tube carcinoma, but in multivariate analyses, only hCGbeta is a prognostic factor independent of stage and histology.

Adult↗

Evidence for the synthesis and secretion of a CBG-like serpin by human cumulus oophorus and fallopian tubes.

The acrosome reaction (AR)-inducing effect of follicular cells, like that of the cumulus oophorus and granulosa cells, has been described previously. In addition to the well known steroid secreting activity of cumulus cells, the results obtained here demonstrate the secretion of a corticosteroid-binding globulin (CBG)-like protein. An AR-inducing effect was shown with the culture medium of human cumulus oophorus. This effect could be eliminated by treating the sample with monoclonal antibodies against CBG. Moreover, Western blotting after SDS-PAGE of the culture medium strongly indicates that human cumulus cells actively express and secrete a CBG-like protein. This might give an indication as to the origin of the acrosome reaction-inducing substance found in follicular fluid. Furthermore, AR-inducing activity and the elimination of this activity by antibodies against CBG was shown for oviductal fluid. With immunohistochemical techniques the CBG-like protein was localized in the epithelial lining of the fallopian tubes, giving possible evidence for the involvement of this molecule in fallopian tube function.

Fallopian Tubes↗

Falloposcopy: a microendoscopic technique for visual exploration of the human fallopian tube from the uterotubal ostium to the fimbria using a transvaginal approach.

A transvaginal microendoscopic technique has been developed for safely exploring the human fallopian tube from the utero tubal ostium to the fimbria and adjacent peritoneal cavity. Falloposcopy was performed without complication or evidence of endotubal damage in 44 women, 38 of whom also underwent a concurrent laparoscopy. Eight women with normal tubes served as controls and 36 women with tubal damage underwent falloposcopy in an attempt to document endotubal defects. Previous salpingectomy in 13 women and ostial obstruction in 4 cases left 71 tubes available for falloposcopy. Technical failures, defined as an inability to negotiate the tubal lumen in the absence of obstructive disease occurred in 8 of 71 (11%) procedures. In 63 successful procedures, the tubal lumen was considered to be falloposcopically normal in 28 cases (44%) and contained defects ranging from partial to total obstruction secondary to intraluminal fibrosis within the intramural, isthmic, and ampullary segments in the remaining 35 tubes (56%). Falloposcopy provides a nonincisional modality for defining the normal and abnormal surface anatomy of the tubal epithelium.

Endothelium↗

Occult cancer of the fallopian tube in a BRCA2 germline mutation carrier at prophylactic salpingo-oophorectomy.

BACKGROUND: Women with a germline BRCA1 or BRCA2 mutation have a significantly increased risk of developing ovarian cancer compared with women in the general population and may consider bilateral prophylactic oophorectomy as a risk-reducing option. CASE: We report a case of occult fallopian tube cancer diagnosed at prophylactic surgery in a patient with a BRCA2 mutation. CONCLUSIONS: This report acts as a reminder of the importance of removing as much of the fallopian tube as possible during prophylactic surgery in BRCA1 and BRCA2 carriers and of the need for careful pathological examination of surgical specimens after surgery.

Fallopian Tube Neoplasms↗