Immunosuppressive effect of serum in patients with ovarian carcinoma.

Cell-mediated immune response was measured in 23 patients with ovarian cystadenocarcinoma, 38 patients with benign ovarian tumor, and 44 healthy volunteers. The method used two indexes: the lymphocyte response per unit volume of peripheral blood to phytohemagglutinin (PHA) and the immunosuppressive effect of serum on the response of normal lymphocytes to PHA stimulation. The lymphocyte response per 50 microliter peripheral blood did not differ significantly between patients with ovarian cancer and healthy volunteers. The serum effect, in contrast, differed significantly between malignant and benign ovarian tumors, and was found to increase significantly even when the cancer masses were as small as about 5 x 5 x 5 cm in size, ie, in FIGO Stage I. It is our belief that the measurement of the serum effect in patients with any ovarian tumor enables the early detection of ovarian cancer.     

MR and ultrasound imaging of floating globules in mature ovarian cystic teratoma

A rarely reported case of cystic teratoma with floating globules or fat balls is presented. Comparative imaging investigations of the floating globules in an ovarian cystic teratoma were performed using magnetic resonance and two- and three-dimensional ultrasound. Ultrasound imaging easily detected the floating globules, especially the 3-dimensional features showed almost the same findings that were observed macroscopically after surgery. Magnetic resonance thus clearly revealed the character of floating globules.     

Decreased type I collagen expression in human uterine cervix during pregnancy

To provide some insight into the mechanism of cervical ripening, the expression of type I collagen was investigated in human uterine cervical tissues obtained from the first (n = 4) and third (n = 3) trimesters of normal pregnancy. Indirect immunofluorescent staining was performed for type I collagen, and Northern blot analysis was done to assess expression of mRNA for the alpha1(I) chain. Collagens were also extracted from the human cervical tissues in the first and third trimesters of pregnancy. Immunohistochemical analysis revealed loose distribution of type I collagen in the uterine cervix of the first trimester compared with the third trimester of pregnancy. The relative levels of various collagens were evaluated by SDS-PAGE. The ratios of the intensity of the band of alpha1(I) to that of total collagen alpha1 chain in cervical tissues of the third trimester were significantly lower than those in cervical tissues of the first trimester of pregnancy (P < 0.05). In contrast, the ratios of the intensity of the band of alpha1(III) to that of total collagen alpha1 chain in cervical tissues of the third trimester were significantly higher than those in cervical tissues of the first trimester of pregnancy (P < 0.05). Northern blot analysis revealed that the cervical expression of mRNA for the alpha1(I) chain was significantly reduced in the third trimester compared with the first trimester of pregnancy (P < 0.01). These results suggest that type I collagen might play an important role in the maintenance of pregnancy and that decreased expression of this collagen could be associated with the process of uterine cervical ripening.     

A novel molecular mechanism for anticancer drug-induced ovarian failure: Irinotecan HCl, an anticancer topoisomerase I inhibitor, induces specific FasL expression in granulosa cells of large ovarian follicles to enhance follicular apoptosis

Clinical use of CPT-11 combination chemotherapy frequently induces ovarian dysfunction in premenopausal and perimenopausal cancer patients, but its mechanism remains unclear. Mouse experiments were performed to clarify the molecular mechanism of CPT-11-induced ovarian dysfunction. Clinically therapeutic doses of CPT-11 were injected intraperitoneally into 8-week-old female MCH mice, and their ovaries were examined by the TUNEL assay to detect dead cells. Immunohistochemical examinations were simultaneously performed to detect the expression of activated caspase 3, Fas antigen and Fas ligand (FasL). Furthermore, normal murine ovarian tissue fragments were incubated with recombinant soluble FasL in organ cultures and stained by the TUNEL assay to detect apoptotic cells. Intraperitoneal CPT-11 injections induced specific TUNEL-positive cells and cell death with cleaved caspase 3 expression among large ovarian follicular granulosa cells. Apoptotic follicles (follicles containing >/=10 TUNEL-positive cells per ovarian section) were only found among large follicles. The final apoptotic follicle ratios were approximately 30% of the total follicles independent of the CPT-11 dose, while CPT-11 dose-dependently enhanced apoptotic processes in murine ovarian follicles. Fas antigen was expressed in most ovarian cells, with extremely high expression levels detected in luteal cells. CPT-11 injections did not significantly increase the Fas expression levels in ovarian cells. Although no FasL expression was detected in normal ovarian tissues, CPT-11 injections significantly induced specific FasL expression in granulosa cells. Incubation of organ-cultured normal murine ovarian tissue fragments with recombinant mouse soluble FasL significantly increased the numbers of TUNEL-positive granulosa and luteal cells. In conclusion, CPT-11 dose-dependently induced specific FasL expression in granulosa cells of developing ovarian follicles. The induced FasL reacted with the Fas antigen constitutively expressed on granulosa cells, such that apoptosis can only be enhanced and induced in granulosa cells in an autocrine and/or paracrine manner. This cell lineage-specific and differentiation stage-specific apoptosis in granulosa cells is thought to be the main molecular mechanism of the ovarian dysfunction induced by CPT-11 combination chemotherapy.     

Increased natural killer cell activities in patients treated with gonadotropin releasing hormone agonist.

Natural killer (NK) cell activity in patients treated with gonadotropin-releasing hormone agonists (GnRH-a) was studied. The subjects were 8 patients with endometriosis (6 with ovarian endometrial cyst, 2 with adenomyosis) and 3 patients with uterine leiomyoma. Changes in serum estradiol (E2) concentration and NK cell activity in peripheral blood were analyzed before and after GnRH-a treatment (buserelin 900 microg/day for 4-5 months). NK cell activity was determined by 51Cr release assay and E2 by radioimmunoassay. NK cell activity before GnRH-a treatment was 37.7 +/- 19.0%, and after therapy activity increased significantly to 50. 8 +/- 18.2%. However, no significant correlation between the increase in NK cell activity and the decrease in E2 concentration was found. Results indicate that the standard GnRH-a treatment for endometriosis and uterine leiomyoma might increase NK cell activity. The etiology of the increase of NK activity with GnRH-a treatment is likely related to factors other than E2 concentration.     

Prospective Study to Compare Endometrial Cytology and Transvaginal Ultrasonography for Identification of Endometrial Malignancies

We compared transvaginal ultrasonography (TVS) and endometrial cytology by the Endocyte method for endometrial cancer screening. A total of 600 postmenopausal women who hoped for endometrial cancer screening (mean age, 61.1 ± 8.8 years; range, 44–87 years) underwent TVS, endometrial cytology (Endocyte method), and endometrial histology. The endometrial borders could be visualized by TVS in all women studied. However, cytology could not be performed in 59 women (9.8%) due to cervical stenosis. These 59 women were excluded from further study. Of the 541 remaining women, 38 had pathologic conditions (16 had endometrial cancer and 22 had endometrial hyperplasia). One (6.3%) of the 16 endometrial cancer patients and 10 (45.5%) of the 22 hyperplasia patients were asymptomatic. One hundred thirty-nine (83.7%) of the 166 women with postmenopausal bleeding had no pathological condition. When the cutoff value of endometrial thickness was set at 4 mm for women <5 years since menopause and 3 mm for those ≧5 years since menopause, TVS showed a 97.4% sensitivity, 75.7% specificity, 23.8% positive predictive value, and 99.7% negative predictive value. Thirty-seven of the 38 patients with endometrial disease were detected by TVS. Eight patients with a benign Endocyte examination were found to have endometrial hyperplasia. However, all endometrial cancers were detected by cytological examination. The Endocyte method exhibited 78.9% sensitivity, 95.4% specificity, 56.6% positive predictive value, and an 88.5% negative predictive value. In conclusion, TVS is thought to be useful for identification of patients who required further diagnostic investigation including endometrial histology.     

Enhancement of human endometrial stromal decidualization by bestatin, an aminopeptidase-N inhibitor.

We have re-evaluated the effects of bestatin, an aminopeptidase-N (CD13) inhibitor, on in vitro decidualization of normal human endometrial stromal cells by using an in vitro decidualization activity assay. Bestatin did not show any effects on the viability of both the decidualizing stromal cells co-stimulated with 8-Br-cAMP and bestatin and the 8-Br-cAMP-induced decidualized stromal cells, or on prolactin release from the decidualized stromal cells. However, bestatin dose-dependently enhanced prolactin release from the decidualizing stromal cells co-stimulated with 8-Br-cAMP and bestatin. These results indicate that bestatin enhances cAMP-mediated decidualization of human endometrial stromal cells and suggests that membrane aminopeptidase-N in the human endometrium is involved in the regulation of endometrial differentiation by inhibiting cAMP-mediated decidualization signals in endometrial stromal cells.     

Combined diagnostic imaging of uterine carcinosarcoma: A case report

Abstract. Umesaki N, Tanaka T, Miyama M, Ogita S, Ochi H. Combined diagnostic imaging of uterine carcinosarcoma. A case report.
The diagnostic imaging characteristics of uterine carcinosarcoma have not been established because the tumor is very rare. We studied magnetic resonance (MR) imaging, power Doppler ultrasonography, and positron emission tomography (PET) in one such carcinosarcoma to define its imaging characteristics. On T1-weighted MR images, the tumor mass in the uterus was low-signal intensity and had a slight inhomogeneous appearance. On T2-weighted images, it had a heterogeneous appearance and was of medium- or high-signal intensity; marked flow void was apparent from the myometrium to the tumor mass. The MR flow void was also detected by power Doppler ultrasonography. Increased glucose metabolism was detected on PET images, suggesting a malignant tumor in the endometrial cavity. Combined diagnostic images with MR, power Doppler ultrasonography, and PET is recommended as the diagnostic method for uterine carcinosarcoma.     

Spatiotemporal signatures of an abnormal auditory system in stuttering

People who stutter (PWS) can reduce their stuttering rates under masking noise and altered auditory feedback; such a response can be attributed to altered auditory input, which suggests that abnormal speech processing in PWS results from abnormal processing of auditory input. However, the details of this abnormal processing of basic auditory information remain unclear. In order to characterize such abnormalities, we examined the functional and structural changes in the auditory cortices of PWS by using a 306-channel magnetoencephalography system to assess auditory sensory gating (P50m suppression) and tonotopic organization. Additionally, we employed voxel-based morphometry to compare cortical gray matter (GM) volumes on structural MR images. PWS exhibited impaired left auditory sensory gating. The tonotopic organization in the right hemisphere of PWS is expanded compared with that of the controls. Furthermore, PWS showed a significant increase in the GM volume of the right superior temporal gyrus, consistent with the right tonotopic expansion. Accordingly, we suggest that PWS have impaired left auditory sensory gating during basic auditory input processing and that some error signals in the auditory cortex could result in abnormal speech processing. Functional and structural reorganization of the right auditory cortex appears to be a compensatory mechanism for impaired left auditory cortex function in PWS.