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Biomedical subjects

A Yajima

Publications and source records attributed to A Yajima.

At least 73 records · Page 4Linked to original sources

Leukocytes in normal-cycling human ovaries: immunohistochemical distribution and characterization.

We investigated, using an image analysis system, the immunohistochemical localization of leukocyte subpopulations and human leukocyte antigen (HLA)-DR in 30 normal-cycling human ovaries in order to better understand local immunological events in human ovaries. All subtypes of T lymphocytes examined (CD3+, CD4+ and CD8+ cells) were sporadically observed in the stroma and theca layers of follicles throughout the menstrual cycle (ranging from 4.32 to 6.25 cells/10(-7) m2, 1.67 to 3.33 cells/10(-7) m2 and 2.33 to 3.44 cells/10(-7) m2, respectively for the three subtypes), and subsequently, increased in number in atretic follicles (78.70 +/- 6.90, 31.13 +/- 2.54 and 43.31 +/- 3.35). After ovulation, the number of T lymphocytes was markedly low in the early and mid corpus luteum (13.88 +/- 1.62, 4.18 +/- 0.50 and 6.53 +/- 0.45). The number increased in the late corpus luteum, and was highest in the late degenerating corpus luteum (255.67 +/- 27.10, 102.12 +/- 7.80 and 137.34 +/- 12.50). HLA-DR was sporadically positive in fibroblasts in the stroma and theca layers of follicles (means ranged from 1.25 to 1.82 cells/10(-7) m2), and increased in atretic follicles (24.68 +/- 2.25). HLA-DR+ cells were markedly low in the early and mid corpus luteum (2.16 +/- 0.88), increased in the late corpus luteum, and reached a plateau in the late degenerating corpus luteum (121.84 +/- 17.73). The great majority of these increased HLA-DR+ cells were macrophages. Results of our study suggest that T lymphocytes and/or macrophages play important roles in luteal regression and follicular atresia in normal-cycling human ovaries.

Adult↗

The PTEN, BAX, and IGFIIR genes are mutated in endometrial atypical hyperplasia.

To pursue the pathogenesis of endometrial carcinogenesis, we investigated microsatellite instability, mutations in the PTEN, TGF beta RII, IGFIIR, and BAX genes, and LOHs on 10q in 18 putative endometrial premalignant lesions (11 endometrial atypical hyperplasias (ATHs), 2 complex hyperplasias, and 5 simple hyperplasias) as well as 8 endometrial cancers (ECs). In the ATH cases, MSIs as well as LOHs at 10q were observed at frequencies similar to those in ECs. Mutations in PTEN, BAX, and IGFIIR were observed only in ATHs and ECs. These results suggest that (1) PTEN, BAX, and IGFIIR are already mutated in ATHs, and (2) ATH is one of the precursor lesions which could lead to EC.

Endometrial Neoplasms↗

Malignant rhabdoid tumor of the vulva: case report with cytological, immunohistochemical, ultrastructural and DNA ploidy studies and a review of the literature.

A case of malignant rhabdoid tumor of the vulva in a 25-year-old female was examined. The patient presented with a subcutaneous nodule in the left labium majus. Smears of the material obtained by percutaneous fine-needle aspiration demonstrated clusters of atypical cells with prominent nucleoli. The tumor measured 6 x 5 x 5 cm and appeared tan to brown on the cut surface and partly cystic. Pathological findings obtained from intraoperative frozen tissue sections had been originally interpreted as rhabdomyosarcoma. Light microscopic examination revealed that polygonal tumor cells having vesicular nuclei with prominent nucleoli were arranged in sheets and the great majority of the tumor cells contained an eosinophilic globular paranuclear cytoplasmic inclusion. Ultrastructurally, this cytoplasmic inclusion corresponds to whirls of intermediate filaments. Vimentin immunoreactivity was detected in both the cytoplasm and cytoplasmic inclusion of almost all the tumor cells. No cytokeratin and desmin immunoreactivity were detected in the tumor cells. The Ki-67 labeling index was 36% and the DNA content of the tumor cells, which was examined by image cytometry, demonstrated diploidy (DNA index = 0.95).

Adult↗

Ovarian mixed germ cell tumor composed of dysgerminoma, endodermal sinus tumor, choriocarcinoma and mature teratoma in a 44-year-old woman: case report and literature review.

A case of ovarian mixed germ cell tumor in a 44-year-old woman was examined. The tumor was well circumscribed, measured 15 x 11 x 10 cm and appeared solid and partly cystic on the cut surface. Light microscopic examinations revealed that the tumor was composed of four different neoplastic germ cell elements, intermingled with each other. They are: (i) choriocarcinoma, immunohistochemically positive for human placental lactogen (hPL) and human chorionic gonadotropin (hCG); (ii) dysgerminoma, positive for placental alkaline phosphatase; (iii) endodermal sinus tumor positive for alpha-fetoprotein (AFP); and (iv) mature teratoma. Among these histological types, dysgerminoma occupied more than 50% of the neoplasm. The patient was diagnosed as a stage la ovarian mixed germ cell tumor and was subsequently treated with chemotherapy. A second-look laparotomy after completion of chemotherapy revealed no residual tumors in the abdomen and the patient is alive and well 15 months after operation. This is the fourth reported case of ovarian mixed germ cell tumor arising in patients over 40 years old.

Adult↗

Increased mast cell density in peritoneal endometriosis compared with eutopic endometrium with endometriosis.

PROBLEM: Factors regulating fibrosis in peritoneal endometriosis are poorly understood. We hypothesized that mast cell proteases may play a role in the process of fibrosis in peritoneal endometriosis. As the first step in examining the possible contribution of mast cells to fibrosis, we investigated their distribution in peritoneal endometriosis lesions according to their macroscopic appearance. METHOD OF STUDY: Mast cells were identified by immunohistochemistry using monoclonal antibody against mast cell tryptase on formalin-fixed, paraffin-embedded sections. Mast cell density (mean mast cell count per 0.13 mm2 of stroma) was measured using a computerized image analysis system. RESULTS: Mast cell density was significantly increased in black peritoneal lesions compared with red peritoneal lesions in endometriosis. CONCLUSIONS: Mast cells may be involved in the pathogenesis of peritoneal endometriosis.

Chymases↗

Time-frequency analysis of fetal heartbeat fluctuation using wavelet transform.

We examined whether the nonlinear control mechanism of the fetal autonomic nervous system would change in various fetal states. Eight thousand or more fetal heartbeats were detected from normal, hypoxemic, and acidemic fetuses. Fetal heart Doppler-signal intervals were determined in a high-precision autocorrelation method, and a time series of fetal heart rate fluctuation was obtained. The distribution of the amplitude of temporal fluctuation in the low-frequency component of fetal heart rate frequency was studied using a method of time-frequency analysis called wavelet transform. Spline 4 was used as the mother wavelet function. A gamma distribution was observed from 17 wk of gestation onward. The value of the parameter nu of this gamma distribution was approximately 1.6 and remained constant regardless of the gestational age or the time of day. The value of nu decreased significantly to 0.77 when the fetus developed acidemia and was 1.51 in hypoxemia and 1.54 in a normal condition. This study elucidates a nonlinear structure of the time series of heart rate fluctuation of the gamma distribution in the human fetus. This technique may provide a new quantitative index of fetal monitoring to diagnose fetal acidemia.

Female↗

Growth hormone improves mouse embryo development in vitro, and the effect is neutralized by growth hormone receptor antibody.

We investigated whether growth hormone(GH) may influence the development of mouse embryo in vitro using recombinant GH and anti-growth hormone receptor(GHR) antibody. When mouse two-cell-stage embryos were cultured with GH, 5, 10 mIU/ml, the rates of formation of both blastocysts and of hatched blastocysts from two-cell-stage embryos were significantly higher than in the medium without GH. The number of blastomeres from blastocyst treated with GH, 2, 5 and 10 mIU/ml, was significantly higher than those cultured without GH. When cultured blastocysts were implanted in recipient uteri, a significantly higher implantation rate was found for the GH-treated(10 mIU/ml) mouse embryos than for controls. To confirm the GH effect, anti-GHR monoclonal antibody MAb5 was employed to neutralize the action of GH through GHR. Two-cell-stage mouse embryos were cultured with GH, 10 mIU/ml, and anti-GHR antibody, and as a control, embryos were cultured with GH alone. Both the rate of formation of blastocysts from two-cell-stage embryos and the number of blastomeres were significantly decreased in groups exposed to anti-GHR antibody. Results indicate that GH may be important to early embryonic development, acting through GHR. GH may help to obtain good quality embryos and improve the implantation rate in IVF programs.

Animals↗

Massive intraperitoneal hemorrhage and hypovolemic shock due to rupture of a coronary vessel of a uterine leiomyoma: a report of two cases.

Intraperitoneal hemorrhage due to uterine leiomyoma is extremely rare. Recently, we encountered such two cases and herein describe them. Case 1 involved a 34-year-old, nulliparous woman referred to our hospital because of a sudden onset of shock while she was playing a softball game. She had a large abdominal tumor and a hemoperitoneum, and was diagnosed as having a ruptured ovarian tumor. Exploratory laparotomy showed a rupture of the coronary vein of a large uterine leiomyoma. The patient was treated with myomectomy and did well postoperatively. Case 2 involved a 44-year-old, multiparous woman referred to our hospital because of sudden onset of lower abdominal pain while defecating. She had a uterine leiomyoma and a hemoperitoneum, and was diagnosed as having a ruptured splenic artery. Exploratory laparotomy showed rupture of the coronary artery of a uterine leiomyoma. The patient was treated with total abdominal hysterectomy and did well postoperatively. These cases suggest that intraperitoneal hemorrhage associated with uterine leiomyoma, although rare, should be considered in women with hypovolemic shock and a large pelvic mass.

Adult↗

The effect of cold stress on uterine artery blood flow velocity waveforms in late pregnant women with and without preeclampsia.

Cold stimulus, immersing the hand into ice water, was given to pregnant women with and without preeclampsia. The uterine artery blood flow was observed before, during and after the stimulus by Doppler ultrasound. The pulsatility index in the uterine artery blood flow was significantly increased by the cold exposure in preeclampsia from 1.14 to 1.52, whereas it increased in normal control from 0.95 to 1.25. In two of 11 cases of preeclampsia with fetal growth restriction, cold stimulus to the mother elicited a decrease of variability on fetal heart rate monitoring. Cold stimulus induces the constriction of the uterine artery, leading to a decrease of placental blood flow.

Adult↗

Analysis of clonality in human endometriotic cysts based on evaluation of X chromosome inactivation in archival formalin-fixed, paraffin-embedded tissue.

The clonality of epithelial cells in ovarian endometriotic cysts was evaluated on the basis of a polymorphism of the X-linked phosphoglycerate kinase gene (PGK). The problems associated with clonality analysis of DNA samples extracted from archival formalin-fixed, paraffin-embedded tissue were addressed with the use of newly designed primers and a modified stepdown program for PCR amplification. The method relies on digestion of DNA with the methylation-sensitive restriction enzyme SnaBI, PCR amplification of PGK, and detection of a BstXI polymorphism. With this approach, only the inactive (methylated) PGK allele is selectively amplified by PCR. A total of 25 epithelial cells in endometriotic cysts and 25 matched normal ovarian stromal tissue specimens were analyzed. All of the control tissue samples yielded PCR products, with 11 of the 25 samples found to be heterozygous for the BstXI polymorphism. Ten of the 25 epithelial cells in endometriosis specimens were informative at this locus, and all of these 10 were shown to be monoclonal on the basis of PGK methylation. The results indicate that this new method of clonal analysis with archival formalin-fixed tissue is reliable and confirm that endometriotic cysts are monoclonal in origin.

Base Sequence↗

Immunohistochemical and two-parameter flow cytometric studies of DNA topoisomerase II alpha in human epithelial ovarian carcinoma and germ cell tumor.

DNA topoisomerase II alpha (topo II alpha) is associated with active cell proliferation and is a target for chemotherapeutic agents administered to patients with ovarian cancer. To evaluate the biologic significance of topo II alpha expression in human ovarian carcinomas, we examined the expression of this protein immunohistochemically in tissue sections from 99 patients with ovarian cancer (85 common epithelial carcinomas, 14 germ cell tumors). We also measured topo II alpha and nuclear DNA content by two-parameter flow cytometry in 29 cases to evaluate possible qualitative changes of topo II alpha in the cell cycle of ovarian cancer cells. We observed a significant correlation of the labeling indices (LIs) of topo II alpha and Ki-67. The topo II alpha-to-Ki-67 ratio in germ cell tumors significantly exceeded that in common epithelial ovarian carcinomas (P = .038). Among the latter, the topo II alpha-to-Ki-67 ratio was significantly higher in serous cystadenocarcinomas than in mucinous cystadenocarcinomas. Two-parameter flow cytometric analysis revealed that topo II alpha expression was mainly observed in cells at the S to G2/M phases of the cell cycle, but, in some cases, topo II alpha positivity was detected in cells at G1. A significantly higher topo II alpha-to-Ki-67 ratio was detected in tumors with topo II alpha-positive cells at the G1 than in tumors in which topo II alpha-positive cells were not at G1. Results indicated that quantitative as well as quantitative changes in topo II alpha occur in human ovarian carcinomas.

Adult↗

[Effect of 5'-DFUR used concurrently in radiotherapy and immunotherapy uterine cervical cancer--pilot study. Study of 5'-DFUR for Uterine Cervical Cancer].

We conducted a preliminary controlled study in order to evaluate 5'-DFUR dose dependency in efficacy and safety in combination therapy of radiotherapy, 5'-DFUR and SPG for patients with uterine cervical cancer, which was regarded as suitable for cases of radiotherapy. The patients were randomly allocated into group A (5'-DFUR 600 mg/body/day) and group B (5'-DFUR 800 mg/body/day), who underwent radiotherapy with simultaneous administration of 5'-DFUR and SPG (20 mg twice/week or 40 mg/ week). Those enrolled were 33 patients in stage II, III or IV a with histologically diagnosed primary squamous cell carcinoma of uterine cervix. CR was shown in 19, PR in 7, NC in 1, and PD in 2 out of 29 efficacy-evaluable cases, so the overall response rate was 89.7% (26/29, 95% CI 72.7%-97.8%). Regarding safety, some side effects were observed in 26 out of 33 safety-evaluable cases (81.3%, 95%, CI 63.6%-92.8%), but no serious cases. No significant difference in efficacy and safety was observed between the two treatment groups. These results suggested that the combination therapy of radiotherapy, 5'-DFUR and SPG might be one of the therapies whose effectiveness must be confirmed for advanced squamous cell carcinoma of uterine cervix. To confirm dose dependency of 5'-DFUR, it seems further consideration with more patients is needed.

Adjuvants, Immunologic↗

HPV, histologic grade and age. Risk factors for the progression of cervical intraepithelial neoplasia.

OBJECTIVE: To evaluate the clinical significance of human papillomavirus (HPV) type, grade of cervical intraepithelial neoplasia (CIN) and age on the progression of CIN. STUDY DESIGN: Clinical follow-up data, histopathologic diagnosis, polymerase chain reaction (PCR) and HPV DNA typing were available on 194 patients, 119 with CIN 2/moderate dysplasia and 75 with CIN 3/severe dysplasia. RESULTS: HPV 16 was observed most frequently (47.0%) in progressed CIN, while HPV-negative cases (57.7%) were most frequently regressed. HPV positivity (P = .0466), especially HPV 16 positivity (P = .0104), was significantly more frequent than HPV negativity in the progression group. The rate of CIN progression was higher with HPV (50.5%) than without HPV (35.4%). Of the CIN cases with HPV 16, 56.5% progressed, while 30.8% of the CIN cases with HPV 6 and/or 11 and 35.4% of the CIN cases without HPV progressed. The probability of progression was 1.87-fold higher in the HPV-positive group than that in the HPV-negative group (P = .03). Multiple logistic regression analysis revealed that HPV (odds ratio 2.23, P = .0103) and grade of the lesion (odds ratio 3.30, P = .0002) in the initial biopsy strongly and independently correlated with progression of CIN. CONCLUSION: HPV status and histologic grade are independent predictive risk factors for progression and may be useful in the management of CIN.

Adult↗

[Characteristics of uterine cancer detected by mass screening].

In Miyagi Prefecture, mass screening for cervical cancer was initiated in 1961. We organized the project in cooperation with the Miyagi Cancer Society. Because cases detected in mass screening were treated earlier, their prognoses were better than cases diagnosed in outpatient clinics. A high proportion of patients detected in stage 0 and I showed improved prognoses. In 1983, the central government established the first Health and Medical Services Law for the Aged to support the project. The standardized death rate of cervical cancer in Miyagi Prefecture fell from 12.1 per 100,000 in 1961 to 4.0 per 100,000 in 1994. A case-control study revealed that women who were screened, compared with women who had no prior screening, had an odds ratio for invasive cervical cancer of 0.14. The time interval of following the last negative smear was assessed, and we found that an odds ratio for a one-year interval was 0.09. However, there still remain problems, such as the lack of a further increase in the screening rate, fixation of examinees, and increase in the incidence of young women. Uterine body cancer is one of the increasing malignancies in Japan, as well as worldwide. Its epidemiological characteristics are as follows; 1) over 50 years old, 2) infertile and irregular menstruation, 3) post-menopause, and 4) atypical genital bleeding. Screening for uterine body cancer was started in 1987 under the second Health and Medical Services Law for the Aged. The target of the screening is limited to cases with the high-risk factors above described. We reported the results of mass screening in Miyagi Prefecture, elucidated the characteristics of uterine cancer detected by mass screening, and indicated the problems.

Adenocarcinoma↗

[Early phase II trial of oral etoposide administered for 21 consecutive days in patients with cervical or ovarian cancer. ETP 21 Study Group--Cervical-Ovarian Cancer Group].

We conducted multi-site early phase II trial or oral etoposide administered for 21 consecutive days in patients with cervical or ovarian cancer in cooperation with 19 institutes. Fifty mg/body of oral etoposide was administered daily for 21 consecutive days. Cycles were repeated every 28 days. In cervical cancer, 24 patients were enrolled and 17 of them were evaluated. The overall response rate including CR and PR was 23.5% (4/17). In ovarian cancer, 18 patients out of 21 enrolled were evaluated. The overall response rate was 16.7% (3/18). The primary toxicity observed was myelosuppression such as leukopenia, neutropenia, hemoglobin decrease and thrombocytopenia. Other adverse effects were anorexia, nausea, vomitting, fatigue, alopecia and stomatitis. From these results we concluded that oral etoposide administered for 21 consecutive days was effective against cervical cancer.

Administration, Oral↗

Identification of a 790-kilobase region of common allelic loss in chromosome 10q25-q26 in human endometrial cancer.

We previously identified two commonly deleted regions on chromosome bands 10q25-q26 in endometrial cancer: an 8-cM region and a 12-cM region. In the present study, we further studied the 8-cM region with 83 endometrial cancer specimens and 14 microsatellite markers and narrowed it down to a 1-cM region between D10S587 and D10S1723. This result was confirmed by two-color fluorescence in situ hybridization analysis. An association between histopathologically lower grade tumor and allelic loss (P = 0.03 by Fisher's exact test) was also observed. We also constructed a yeast artificial chromosome (YAC) contig and found that one YAC clone, which was 790 kb in size, harbored the whole 1-cM region of common allelic loss.

Alleles↗

Correlations between p21 expression and clinicopathological findings, p53 gene and protein alterations, and survival in patients with endometrial carcinoma.

The p21 protein inhibits cyclin-dependent kinases and mediates cell-cycle arrest and cell differentiation. It is induced by wild-type p53, but not by mutant p53. This study of 75 patients with endometrial carcinoma investigates the relationship between p21 expression and the functional status of p53, and the usefulness of p21 as a prognostic marker. Correlations were determined between p21 immunoreactivity, p53 overexpression as examined by immunohistochemistry, p53 DNA mutations as examined by polymerase chain reaction-single-stranded conformation polymorphism (PCR-SSCP) analysis, and clinicopathological features, including the clinical outcome. Immunoreactivity for p21 and p53 mutations were detected in 47 (62.7 per cent), 37 (49 per cent), and 23 (31 per cent) patients, respectively. There were no significant correlations between the presence or absence of p21 immunoreactivity and p53 overexpression and DNA mutations. Survival curves revealed that patients with p53 overexpression tended to have a poorer prognosis than those without p53 overexpression (P = 0.104), that patients with p53 mutations had a significantly worse prognosis than those without mutations (P = 0.035), and that patients with p21 expression tended to have a better prognosis than those without p21 expression (P = 0.074). Immunohistochemical analysis of p21 was not useful for evaluating the functional status of p53 in patients with endometrial carcinoma. Both p21 expression and p53 abnormalities were considered as prognostic indicators in patients with endometrioid endometrial carcinoma.

Biomarkers, Tumor↗

Increased secretion of hepatocyte growth factor by eutopic endometrial stromal cells in women with endometriosis.

OBJECTIVE: We evaluated the secretion of hepatocyte growth factor by eutopic endometrial stromal cells in vitro. DESIGN: Eutopic endometrial stromal cells were isolated and the culture supernatants were collected after 48 hours of incubation. The secretion of hepatocyte growth factor was analyzed by ELISA. SETTING: Department of Obstetrics and Gynecology of Tohoku University Hospital. PATIENT(S): Specimens of endometrium in the proliferative phase were excised from 11 patients who were undergoing laparoscopy for infertility. Six of the patients had endometriosis and five did not. None of the patients had received hormonal treatment before surgery. RESULT(S): Hepatocyte growth factor secretion was found to be increased significantly in cultured endometrial stromal cells from the infertile patients with endometriosis compared with those without endometriosis. CONCLUSION(S): The secretion of hepatocyte growth factor was up-regulated in eutopic endometrial stromal cells from patients with endometriosis. An increase in hepatocyte growth factor production may be characteristic of endometriosis and may be involved in the pathophysiology of this disease.

Adult↗