The behavior of endometrial hyperplasia: a prospective study. Endometrial Hyperplasia Study Group.

Objective: To clarify the behavior of endometrial hyperplasia in a prospective study.

Method: Fifty-one patients with endometrial hyperplasia were followed up for 6 months. Samples of endometrial tissues were taken by uterine endometrial biopsy every 4 weeks during the first 3 months and at the end of follow-up.

Regulation of classical HLA class I genes in human choriocarcinoma cells by nuclear proteins binding to MHC class I regulatory elements.

Problem: The regulation of classical HLA class I genes in choriocarcinoma have been reported.

Methods: We determined whether four choriocarcinoma cell lines expressed classical HLA class I or HLA-G by a reverse transcription-polymerase chain reaction (RT-PCR) and studied the regulatory mechanism of classical class I using a gel mobility shift assay.

Results: NUC1 and SCH expressed classical class I but not HLA-G.

Long-term follow-up of patients with advanced ovarian cancers treated with intermittent administration of combination chemotherapy with cisplatin, doxorubicin and cyclophosphamide.

Despite high primary response rates with cisplatin-based combination chemotherapy, the overall survival rate for advanced ovarian cancers remains dismal. We designed a new systematic treatment approach with a combination chemotherapy consisting of cisplatin, doxorubicin and cyclophosphamide (cyclic PAC chemotherapy), with the aim of improving survival rates with minimal disturbance of quality of life. Cyclic PAC chemotherapy is a three-step chemotherapy with three courses of the PAC regimen in each step.

Acrosome reaction induced in a limited population of human spermatozoa by progesterone (Ca(2+)-dependent) and ATP (Ca(2+)-independent).

We examined the kinetics of the acrosome reaction induced in human spermatozoa by progesterone (Ca(2+)-dependent) and adenosine 5'-triphosphate (ATP; Ca(2+)-independent). ATP and progesterone did not induce the acrosome reaction unless spermatozoa were incubated in a capacitation medium. ATP exhibited a constant induction of the acrosome reaction regardless of the incubation period, while progesterone began to induce the acrosome reaction after > or = 6 h of incubation.

Acrobeads test: a new diagnostic test for assessment of the fertilizing capacity of human spermatozoa.

Objective: To determine the effectiveness of the Acrobeads test for predicting the outcome of IVF.

Design: Human spermatozoa express the CD46 molecule (membrane cofactor protein) on their heads after the acrosome reaction. CD46-positive spermatozoa formed a sperm-bead complex with immunobeads coated with anti-CD46 monoclonal antibody.

Adenosarcomas originating from sites other than uterine endometrium.

We report three cases of adenosarcomas arising from extraendometrium of the uterus: one arising from the ovary, one from the paracolpium and one from the endocervix of the uterus. Microscopically, they consisted of an admixture of benign-appearing epithelial and mesenchymal components with hypercellularity and minimal atypia. Two of the tumors were initially misdiagnosed as endometriosis and one was diagnosed as adenofibroma.

Apoptosis of cultured mouse luteal cells induced by tumor necrosis factor-alpha and interferon-gamma.

Background: Macrophages and T lymphocytes have been identified in the regressing corpus luteum, and they are thought to participate in structural luteolysis (destruction and removal of luteal cells). Since these cells produce cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), we investigated the effects of these two cytokines on death of luteal cells in vitro.

Methods: Mouse luteal cells were cultured in serum-free medium with TNF-alpha at 0, 500, 1,000, 3,000, or 5,000 U/ml in the presence or absence of IFN-gamma at 1,000 U/ml for 3 or 6 days.

Analysis of clonality by amplification of short tandem repeats. Carcinomas of the female reproductive tract.

The clonal composition of cancers of the female reproductive tract was evaluated by analysis of patterns of X-chromosome inactivation. Using DNA extracted from frozen tissues or paraffin-embedded archival specimens as template, polymerase chain reaction (PCR) was performed to generate amplified DNA fragments of exon 1 of the X-linked androgen receptor gene, which contains a highly polymorphic trinucleotide repeat. Predigestion of tumor DNA with methylation-sensitive restriction endonuclease Hha I or Hpa II permitted selective PCR amplification from the methylated (uncleaved) allele.

Alteration of the p53 tumor suppressor gene occurs independently of K-ras activation and more frequently in serous adenocarcinomas than in other common epithelial tumors of the human ovary.

To clarify the role of the p53 tumor suppressor gene in the development of human ovarian epithelial tumors and to study the association of p53 alterations with K-ras activation, a series of 70 common epithelial ovarian tumors from Japanese patients was studied. These included 31 serous adenocarcinomas, 12 mucinous adenocarcinomas, 5 mucinous tumors of borderline malignancy, 13 endometrioid adenocarcinomas, and 9 clear cell carcinomas. Allelic loss, recognized at the polymorphic site in codon 72 of the p53 gene, was detected in 14 of 36 (39%) informative cases by restriction fragment length polymorphism analysis and by single-strand conformation polymorphism (SSCP) analysis of polymerase chain reaction (PCR)-amplified DNA fragments.

Immunohistochemical analysis of p53 in gynecologic tumors.

Immunohistochemical staining for the p53 protein was performed in microwave-fixed, paraffin-embedded sections of normal, premalignant and malignant tissues of the female genital tract using a monoclonal antibody, PAb 1801. No staining was detected in normal and premalignant tissues, whereas nuclear staining of cancer cells was observed in 12 (22%) of 55 cervical squamous cell carcinomas, 4 (25%) of 16 cervical adenocarcinomas, 37 (42%) of 88 endometrial carcinomas, 23 (38%) of 60 ovarian adenocarcinomas, and 6 (100%) of 6 squamous cell carcinomas arising in dermoid cysts. Of interest, 1 of 7 endometrial cancers with concomitant atypical hyperplasia showed weak nuclear staining in a few atypical hyperplastic glands in addition to the cancerous lesions.

Detection of high-risk human papillomavirus in the cervix and semen of sex partners.

To investigate the possibility of sexual transmission of human papillomavirus (HPV), 53 married couples were examined for the presence of HPV-16 and -18 DNAs in the uterine cervix and semen using the polymerase chain reaction method. Twenty-three of the 53 women and 12 of the 53 male partners were positive for HPV-16 DNA. No HPV-18 DNA was detected in samples from any of the partners.

Type-IV collagenase and tissue inhibitor of metalloproteinase in ovarian cancer tissues.

Objective: We examined the specific expression of gelatinase/type-IV collagenase and tissue inhibitor of metalloproteinase (TIMP) in clinical ovarian cancer tissue.

Methods: Molecular weight-specific gelatinase/type-IV collagenase activity was examined by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis in which substrate was included (zymography). The expression of TIMP mRNA was examined by Northern blot analysis.

Clonal analysis of human gynecologic cancers by means of the polymerase chain reaction.

Clonality of human gynecologic cancers was analyzed in small DNA samples prepared from cryostat sections, by means of the polymerase chain reaction (PCR). The method used for clonal analysis was based on restriction fragment length polymorphism of the X-chromosome-linked phosphoglycerokinase (PGK) gene and on the differential methylation of the PGK gene due to random inactivation of 1 of 2 X-chromosomes by methylation in females. Among 52 gynecologic cancers tested, 25 were found to be heterozygous for the BstXI polymorphism of the PGK gene.

Clinicopathological characteristics of p53 overexpression in endometrial cancers.

Using immunohistochemical methods, we analyzed the association between nuclear p53 overexpression and various clinicopathological parameters in patients with endometrial cancers. Formalin-fixed and paraffin-embedded tissue sections from 139 cases of endometrial cancer (endometrioid type, 126; serous papillary type, 12; and clear-cell type, 1) were stained with anti-p53 monoclonal antibody (MAb) DO7. Overexpression of p53 was associated with high malignant potential, including extensive muscular invasion, advanced surgical stage, high histological grade, serous papillary type and a personal history of cancer.

Establishment and characterization of human vaginal malignant melanoma xenotransplants.

Human vaginal malignant melanoma represents rare gynecological malignancies of poor prognosis. We have established a melanoma tumor line in nude mice, designated Mela-1, and have examined the histological and biological characteristics of this tumor. The Mela-1 tumor has preserved the histological, histochemical and biological characteristics of malignant melanoma even after 20 passages.

Loss of biological activity of human chorionic gonadotropin (hCG) by the amino acid substitution on the "CMGCC" region of the alpha-subunit.

In order to study the bioactive sites of the glycoprotein hormones, we have prepared five point mutants on the CMGCC (Cys28-Met29-Gly30-Cys31-Cys32) region of the human alpha-subunit by using site-directed mutagenesis. Each mutant human chorionic gonadotropin (hCG) agr; cDNA and a wild-type hCG beta cDNA were transcribed by T3 RNA polymerase, and the mixture of the hCG alpha mRNA and hCG beta mRNA was microinjected into Xenopus laevis oocytes. All five mutant hCGs produced in oocyte culture supernatants were detected as immunoreactive forms by enzyme immunoassay.

A case-control study on risk factors for uterine endometrial cancer in Japan.

A case-control study of 143 Japanese women with uterine endometrial cancer and 143 individually age-matched controls was conducted to assess the risk factors for endometrial cancers in Japan. Among the characteristics studied, the following factors were significantly greater in the cases than in the controls: nulliparity (odds ratio for parity 1-3 and > or = 4 versus nullipara are 0.40 and 0.

Regulation of early gene expression of human papillomavirus type 16 by inflammatory cytokines.

The host's immune reaction against human papillomavirus (HPV) infection remains poorly understood. Inflammatory cytokines undoubtedly play a key role through activating and coordinating the immune response. However, their direct interactions with the HPV genes remain unclear.

Characterization of rat pituitary cells by their responses to hypothalamic releasing hormones.

Rat pituitary cells in monolayer culture were characterized by their [Ca2+]i responses to hypothalamic releasing hormones, growth hormone (GHRH), thyrotropin-releasing hormone (TRH), gonadotropin-releasing hormone (GnRH) and corticotropin-releasing hormone (CRH). The percentages of the cell population responding to GHRH, TRH, GnRH, CRH and non-responding cells were 27.3%, 47.

Effect of dibutyryl cyclic AMP on morphologic features and marker production of human cervical argyrophil small-cell carcinoma cell line.

The effect of dibutyryl cyclic AMP (dB-cAMP) on the morphologic features and marker production of a human cervical argyrophil small-cell carcinoma (ASCC) cell line was examined. Following 1-5 days' exposure to 5 mM dB-cAMP, morphologic differentiation as defined by the expression of cytoplasmic processes (stellate cells) was observed. The number of stellate cells depended on the dose of dB-cAMP and incubation time.

An experimental model for ovarian tumor invasion of cultured mesothelial cell monolayer.

Background: Peritoneal spread of tumor cells is one of the characteristic features of biologic behavior of ovarian cancers. To understand the mechanism by which human tumor cell invasion takes place, we have tried to establish an in vitro experimental model for ovarian tumor cell invasion of the mesothelial cell monolayer.

Experimental Design: Mesothelial cells were isolated from normal rat mesentery by trypsin digestion and the cells (1 x 10(5)/dish) were cultured in Eagle's minimum essential medium supplemented with 10% fetal calf serum.