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Biomedical subjects

A Yajima

Publications and source records attributed to A Yajima.

At least 91 records · Page 5Linked to original sources

A Turner syndrome woman with a ring X chromosome [45,X/46,X,r(X)(p22.3q27)] whose child also had a ring X chromosome.

OBJECTIVE: To describe a woman with Turner syndrome with ring X chromosome mosaicism who had a child who possessed the same ring X chromosome. DESIGN: Polymorphisms of genes located on the X chromosome from genomic DNA of the mother, father, and the child were evaluated. PATIENT(S): The mother's karyotype was 45,X [48]/46,X,r(X)(p22.3q27) [2], and the child's karyotype was 45,X[33]/46,X,r(X)(p22.3q27) [17]. INTERVENTION(S): Polymerase chain reaction was used to amplify short tandem repeats from the loci of the hypoxanthine phosphoribosyltransferase gene and the androgen receptor gene. RESULT(S): Alleles for both genes in the child originated from both parents in a heterozygous fashion. The alleles originating from the mother originated from the ring X chromosome. However, the amount of amplified DNA was less than that of a normal X chromosome. CONCLUSION(S): The ring X chromosome of the mother was most likely transmitted to the newborn. Thus, an ovum with the ring X chromosome can be fertile and can produce a viable zygote.

Adult↗

Effects of frequent intranasal administration of adjuvant-combined influenza vaccine on the protection against virus infection.

In previous papers, we have shown that Escherichia coli heat-labile enterotoxin B subunit, supplemented with a trace amount of the holotoxin (LTB*) could be used as a potent adjuvant for a nasal influenza HA (haemagglutinin) vaccine in humans. The present study was designed to determine whether the effectiveness of a combined LTB*-HA vaccine could be limited by preexisting immunity to LTB and how many times the adjuvant-combined vaccine could be administered intranasally without reducing its protective efficacy in BALB/c, C3H and B10 mice. The magnitude of both nasal and serum Ab responses to HA vaccine was correlated with the degree of protection against virus infection. Higher doses of LTB*-combined vaccine were required for inducing high enough levels of anti-HA Ab responses to provide complete protection in low responder mice. Repeated pretreatments with LTB* alone (more than six times), which provided high levels of preexisting Abs to LTB, inhibited the induction of anti-HA Ab responses and reduced the protective efficacy of the adjuvant-combined vaccine. However, the LTB*-combined vaccine could be given repeatedly (about ten times) to mice without reducing the effectiveness of the adjuvant-combined vaccine. These results suggest that the LTB*-combined nasal influenza vaccine can be given to humans once every few years when an epidemic of influenza may occur.

Adjuvants, Immunologic↗

Macrophages in normal cycling human ovaries; immunohistochemical localization and characterization.

We evaluated the immunolocalization and characterization of macrophages in 28 normal cycling human ovaries. Two primary antibodies were used to detect the macrophages: PGM1, a general marker for macrophages, and 25F9 which is specific for phagocytosing macrophages. Spindle-shaped cells positive for PGM1 but negative for 25F9 were observed in the stroma (123.6 +/- 1.05 cells/10(-6) m2) and theca layer of the follicle (mean ranged from 22.61 to 53.79) and the number of these cells did not change throughout the cycle. After ovulation, PGM1 positive cells with ballooning bodies began to appear in the early corpus luteum (111.8 +/- 0.83). The number of these macrophages increased in the mid and late corpora lutea, and reached maximum in the early degenerating corpus luteum (1231.0 +/- 3.29). A lower number of PGM1 positive ballooning macrophages were observed in the atretic follicle (177.9 +/- 1.42). 25F9 positive cells were also observed among the PGM1 positive balloon-shaped cells. The number of cells double positive for 25F9 and PGM1 was observed in the mid corpus luteum (44.6 +/- 0.46), increased in the late corpus luteum and early degenerating corpus luteum, and reached plateau in the late degenerating corpus luteum (549.0 +/- 5.82). A lower number of these double positive macrophages were also observed in the atretic follicle (64.8 +/- 0.36). The ratio of 25F9 to PGM1 positive cells increased in parallel with ageing of the corpus luteum (0.19 in the mid corpus luteum, 0.39 in the late corpus luteum, and 0.37 in the early degenerating corpus luteum), and the great majority of PGM1 positive cells were also immunopositive for 25F9 in the late degenerating corpus luteum (0.81). These results suggest that in normal cycling human ovaries, macrophages are mainly involved in luteal regression as scavengers.

Antibodies, Monoclonal↗

Hepatocyte growth factor stimulated proliferation, migration, and lumen formation of human endometrial epithelial cells in vitro.

Human endometrial regeneration has been considered to be modulated by several growth factors. However, little is known about the detailed mechanisms involved in the repair of the endometrium during the menstrual period. Hepatocyte growth factor (HGF) is a pleiotropic growth factor that reportedly acts on various epithelial cells. In the present study, we observed HGF and mRNA expression in human endometrium and mRNA expression in cultured endometrial epithelial cells of the c-met gene by reverse transcription-polymerase chain reaction and Southern blot hybridization. We also examined the biological role of HGF on the regeneration of the endometrium by using cultured endometrial epithelial cells in their proliferative phase. With the proliferation assay, the addition of 10-50 ng/ml of HGF showed that HGF was mitogenic in a dose-dependent manner. With Boyden's chamber technique, 50 ng/ml of HGF significantly stimulated cell migration. In a three-dimensional cell-culture system, the endometrial epithelial cells formed cell clusters and gradually formed epithelial lumens, both of which were stimulated by 50 ng/ml of HGF. Results suggest the HGF stimulates the proliferation and migration of, and morphogenic changes in, endometrial epithelial cells. HGF may modulate the regeneration of the endometrium during menstruation.

Adult↗

Expression of epidermal growth factor-related proteins and epidermal growth factor receptor in common epithelial ovarian tumors.

The biologic significance of epidermal growth factor (EGF)-related proteins and EGF receptor (EGFR) in the development and progression of human ovarian carcinoma was studied in 7 ovarian cystadenomas, 6 mucinous tumors of low malignant potential (LMP), and 25 invasive adenocarcinomas by immunohistochemistry. Results were correlated with clinicopathologic features. We also examined immunoreactivity in five serous adenocarcinomas both before and after cisplatin chemotherapy. Amphiregulin (AR) expression was observed only in mucinous tumors (4 of 8 cystadenomas, 2 of 6 tumors of LMP, and 6 of 10 cystadenocarcinomas), but was not detected in the serous tumors or clear cell adenocarcinomas. EGF, cripto, and EGFR expression was significantly higher in mucinous cystadenocarcinomas than in mucinous cystadenomas or mucinous tumors of LMP. Three of five specimens obtained at a second operation after chemotherapy had more intense or diffuse immunostaining for transforming growth factor alpha (TGF-alpha) than the initial specimens did. Coexpression of more than two of the EGF-related proteins or EGFR significantly correlated with increased surgical stage in serous and clear cell carcinoma. AR expression seems to correlate with mucinous differentiation rather than with advanced stages of ovarian tumors. Our results indicate that expression of some EGF-related proteins is greater in certain subtypes of ovarian carcinomas than in their benign counterparts and that coexpression of these proteins is associated with advanced stage in serous and clear cell carcinoma. Increased TGF-alpha expression may also be related to ovarian tumor resistance to cisplatin chemotherapy.

Adenocarcinoma↗

Adrenal rest tumor of the broad ligament: case report with immunohistochemical study of steroidogenic enzymes.

An adrenal rest tumor of the broad ligament was studied in a 43-year-old woman. The tumor measuring 6 x 3 x 3 cm and appearing as golden-yellow on the cut surface was incidentally discovered during a total hysterectomy due to uterine leiomyoma. The encapsulated tumor was predominantly composed of pale and lipid-rich cells arranged in alveolar clusters or short blunt cords. Electron microscopic examination revealed mitochondria with tubulo-vesicular cristae and abundant lipid droplets. Adrenal 4-binding protein, a transcriptional factor of steroidogenesis, was present in almost all of the tumor cells, suggestive of steroidogenic features in the lesion. Immunoreactivity of steroidogenic enzymes involved in adrenocortical steroid production was detected in the tumor cells, suggesting that tumor cells had the potential to synthesize adrenocortical steroids. A relatively low Ki-67 labelling index (3.20 +/- 1.15 per 100 tumor cells) and an absence of necrosis and vascular and/or capsular invasion suggest benignity of the lesion.

Adrenal Rest Tumor↗

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. RESULTS: In 69% (35/51) of the patients histological picture of the endometrium became normal during the observation period. The lesions persisted in 17% (6/35) of the patients with simple hyperplasia, in 25% (1/4) of those with complex hyperplasia, in 14% (1/7) of those with simple atypical hyperplasia, and in 80% (4/5) of the patients with complex atypical hyperplasia. In the remaining 3 patients with simple hyperplasia, the lesions progressed to complex atypical hyperplasia by the end of follow-up, after showing a normal endometrium. CONCLUSION: Most cases of endometrial hyperplasia, except for complex atypical hyperplasia, disappeared spontaneously within a short period of time.

Adult↗

Does apoptosis contribute follicular atresia and luteal regression in human ovary?

We investigated apoptosis in 37 human ovaries from normally cycling women to determine the mechanism of the various stages of follicular atresia and the regression of corpus luteum in human. Apoptosis was examined by 3'-hydroxy nick end-labeling, by immunostaining of an apoptosis-related antigen, Le(y) and by cell death-related genes, bcl-2. Immunoreactivity for Le(y) and nick end-labeling reactive cells were not observed in the follicular and luteal phases, except for scattered cells in the degenerating corpus luteum. On the other hand, immunoreactivity for bcl-2 was observed in the granulosa cells of antral follicles. These results indicated that apoptosis is not obvious through follicular maturation and luteal regression. This may be due to the relatively long process of human follicular growth and atresia.

Adult↗

A case of female adnexal tumor of probable Wolffian origin: histologically, tumor cells showed three different patterns.

We report a 63-year-old woman with a female adnexal tumor of probable Wolffian origin, which arose within the leaves of the broad ligament, connected to the left ovary and the fallopian tube. She remains alive without evidence of disease 2 years after left salpingo-oophorectomy without subsequent adjuvant therapy. Microscopically, tumor cells were arranged in three different patterns; closely packed tubules, solid, and sieve-like. Cells had uniform round or oval nuclei and mitoses were rare. Although the majority of these tumors are benign, a few cases have shown malignant potential. Therefore, such tumors should receive careful follow-up for possible recurrence and/or metastasis.

Broad Ligament↗

In-utero transplantation of fetal hematopoietic cells in the mouse: the effect of donor and recipient gestational maturity.

To investigate the possibility of engrafting fetal liver hematopoietic cells by in utero intraperitoneal transplantation, we transplanted donor cells obtained from mouse fetuses at 13, 15 and 17 days of gestation to mouse fetuses at 15, 16 and 17 days of gestation. Engraftment was assessed by Sry gene amplification of DNA extracted from peripheral blood samples of transplanted mice six weeks after birth. In comparison, we performed an in vitro colony-assay of fetal liver cells at 13, 15, and 17 days of gestation. The incidence of engraftment was significantly higher in cells of 15 days of gestation than in cells of 13 or 17 days of gestation, whereas the colony forming activity decreased gradually from 13 to 15 days of gestation. From these results, we suggest that the 15 day liver contains hematopoietic progenitors which have the specific characteristics required for engraftment by intraperitoneal transplantation.

Animals↗

Cost-effective analysis of mass screening for cervical cancer in Japan.

Cost-effectiveness analysis for cervical cancer screening in Japan was performed to estimate the cost per life-year saved by the screening; cost-effectiveness ratio (CER). The analysis was made using a simulation model to estimate long-term cost and effectiveness of the screening programs. CER of cervical cancer screening was estimated to be US$ 40,604 which was 2.4 times more expensive than that for gastric cancer screening but was about the same as that for colorectal cancer screening. It was within the range of cost-effectiveness of other cancer screening programs financed under the Health and Medical Services Law for the Aged in Japan. We performed sensitivity analysis on the following seven estimates, the screening charge, the sensitivity and the specificity of the screening test, the frequency of carcinoma in situ (CIS) among cases detected in the screening program, the initial cost and the terminal cost for patients with invasive cancer, and the incidence rate of cervical cancer. The sensitivity analysis demonstrated that the screening charge was the most influential factor on CER. CER was fairly stable under various assumptions on the accuracy of the screening test, the frequency of carcinoma in situ (CIS), the treatment cost for patient, and the incidence of cervical cancer. CER was less sensitive to the changes in incidence, even to as low as a 50% decrease of the current figure. Then if the incidence rate becomes 85% of the current figure in 2015, CER would be US$ 48,176 and it was suggested that the cervical cancer screening would remain reasonably cost-effective until the year 2015.

Adult↗

Immunohistochemical study of Ki-67 and DNA topoisomerase II in human endometrium.

Topoisomerase II (topo II) separates the chromosomes at the end of mitosis, and its expression is limited mostly to the S-to-G2/M phases of the normal cell cycle. We examined the expression of topo II immunohistochemically in 56 specimens of the human endometrium that were retrieved from surgical pathology files. Specimens included proliferative phase mucosa (n = 7), secretory phase mucosa (n = 5), nonatypical adenomatous hyperplasia (n = 7), atypical adenomatous hyperplasia (n = 7) and endometrioid adenocarcinoma (n = 30). We calculated the labeling index (LI) for topo II and correlated the findings with the LI for Ki-67. A significant positive correlation was obtained between the Ki-67 and topo II LIs in all of the specimens examined. The levels of the topo II and Ki-67 LIs in secretory phase endometrium were each significantly lower than in the other cases examined. The levels of the topo II and Ki-67 LIs in adenocarcinoma were significantly higher than those in proliferative phase endometrium and nonatypical hyperplasia. There were no significant differences between atypical hyperplasia and adenocarcinoma in the Ki-67 and topo II LIs. The level of the topo II LI in atypical hyperplasia was significantly higher than that in nonatypical hyperplasia, whereas the Ki-67 LI did not differ between atypical and nonatypical hyperplasia. The levels of the Ki-67 LI were significantly higher than those of the topo II LI in proliferative phase endometrium and in nonatypical hyperplasia, but no significant differences were observed between the LIs in atypical hyperplasia and adenocarcinoma. Topo II immunostaining can identify proliferative cells in routinely processed surgical pathology specimens of human endometrium. The relative overexpression of topo II as compared with Ki-67 in adenocarcinoma suggests a dysregulation or qualitative alteration in topo II associated with malignancy, as reported in other tissues. Such over-expression in atypical hyperplasia might reflect the possible premalignant nature of this type of endometrial hyperplasia.

Antigens, Neoplasm↗

K-ras point mutations in endometrial carcinoma: effect on outcome is dependent on age of patient.

Mutations involving the K-ras proto-oncogene are believed to play an important role in the mechanism of tumorigenesis for many human cancers and occur in 10-30% of endometrial carcinomas. In the present study 221 cases of endometrioid endometrial carcinoma obtained from Japanese patients with average follow-up of 41 months were examined for point mutations in codon 12 of K-ras through use of the polymerase chain reaction. In 103 cases lymph node dissection had been performed. K-ras mutations were significantly associated with the presence of lymph node metastases (P < 0.04). Since endometrial carcinoma in premenopausal women generally behaves less aggressively than tumors of similar histologic grade arising in postmenopausal patients, we evaluated the effect of K-ras mutation on outcome in patients stratified into three different age categories (<53 years, premenopausal; 54-59 years, perimenopausal; >60 years, postmenopausal). In the postmenopausal age group (>60 years), the presence of K-ras mutations was statistically significantly associated with patients who died or experienced recurrence (41.2% vs 13.0%; P < 0.03). This was related to a dramatic (greater than eightfold; P = 0.011) increase in the likelihood of adverse outcome between the premenopausal and postmenopausal states for patients whose tumors contained mutant K-ras. These findings point to a possible role for K-ras activation in the mechanism(s) responsible for more aggressive clinical behavior of endometrioid endometrial cancer that is observed in postmenopausal patients.

Adult↗

Expression of epidermal growth factor family proteins and epidermal growth factor receptor in human endometrium.

The biological significance of epidermal growth factor (EGF)-related proteins in the development and progression of endometrioid endometrial carcinoma was studied. Expression of EGF-related proteins including EGF, transforming growth factor-alpha (TGF-alpha), cripto (CR), amphiregulin (AR), and EGF receptor (EGFR) were immunohistochemically examined. Results were then correlated with clinicopathologic findings and steroid receptor status in 12 specimens with normal endometrium, 13 with endometrial hyperplasia, and 40 with endometrioid endometrial carcinoma. EGFR, EGF, TGF-alpha, and CR immunoreactivities were observed in 58.3%, 66.7%, 91.6%, and 66.7% of normal endometrial specimens; 100%, 15.4%, 100%, and 30.8% of endometrial hyperplasia specimens; and 67.5%, 32.5%, 65.0%, and 65.0% of endometrial carcinoma specimens, respectively. AR immunoreactivity was not observed in any of the normal, hyperplastic, or neoplastic endometrium. The presence or absence of EGFR or TGF-alpha in endometrial carcinoma correlated with surgical stage, depth of myometrial invasion, and findings from peritoneal washing cytology. EGF expression significantly correlated with the age of the patients and that of CR with surgical stage and peritoneal washing cytological findings. There was a significant correlation between EGFR and TGF-alpha expression, and between EGF and TGF-alpha. Co-expression of EGFR and TGF-alpha, EGFR and CR, and TGF-alpha and CR in carcinoma specimens significantly correlated with advanced surgical stage, deeper myometrial invasion, and positive peritoneal washing cytology. In normal as well as hyperplastic endometrium, endometrial glands immunohistochemically positive for TGF-alpha were generally positive for ER, but in poorly differentiated endometrial carcinoma, cells positive for TGF-alpha tended to be negative for ER. The results of the present study show that among EGF-related proteins, expression of TGF-alpha and CR seem to be associated with the progression of human endometrioid endometrial carcinoma. Additionally, expression of TGF-alpha became increasingly estrogen independent with increasing histological carcinoma grades.

Adult↗

Adrenal 4-binding protein in common epithelial and metastatic tumors of the ovary.

Adrenal 4-binding protein (Ad4BP) is a transcription factor that regulates the expression of steroidogenic enzymes. Ovarian tumors other than sex cord stromal tumors are occasionally associated with functioning stroma or hormonal abnormalities. To determine the steroidogenic potential of these tumors, the authors determined the immunohistochemical distribution of Ad4BP in 75 patients with primary common epithelial tumors (20 cystadenomas, 15 carcinomas of low malignant potential, and 40 carcinomas), and seven patients with metastatic carcinoma of the ovary. Ad4BP immunoreactivity was observed in intratumoral stromal cells in 3 of 15 (20%) carcinomas of low malignant potential, 26 of 40 (65%) carcinomas, and three of seven (43%) metastatic carcinomas. Ad4BP immunoreactivity was not observed in the stroma of cystadenomas. Among the positive cases, Ad4BP-positive stromal cells were particularly distributed adjacent to invasive carcinomatous glands. Among ovarian carcinomas, mucinous carcinoma showed a significantly higher number of Ad4BP-positive intratumoral stromal cells than did other histological types. Results suggest that invasion of primary or metastatic carcinoma into the ovarian stroma, especially in the case of mucinous carcinoma, may render the stromal cells to acquire the potential of metabolizing and synthesizing steroid hormones.

Breast Neoplasms↗

Aromatase cytochrome P450 gene expression in endometrial carcinoma.

We analysed aromatase gene expression and its regulation in seven cases of endometrioid endometrial carcinoma. Immunohistochemistry revealed the presence of strong aromatase immunoreactivity in the stromal cells of carcinoma in five out of seven cases. A polymerase chain reaction after reverse transcription (RT PCR) revealed varying levels of aromatase transcripts (0.1-27.0 amol ng(-1) total mRNA) in five cases. The alternative use of multiple exons 1 was also examined by identifying various human aromatase transcripts specific for exons 1 in RT-PCR products. Gonadal type or exon 1d was primarily used in three cases in which aromatase overexpression was not detected. The two cases in which fibroblasts type or exon 1b was used with other exons 1 as minor transcripts demonstrated aromatase overexpression in immunohistochemistry and RT PCR analysis. Further studies are required, but alternative splicing as well as use of multiple exons 1 transcripts may result in increased aromatase expression in stromal cells observed in endometrial carcinoma.

Adult↗

Deletion mapping on chromosome 10q25-q26 in human endometrial cancer.

To understand genetic events which play a role in the development and/or progression of human endometrial cancer, we studied allelotypes on all autosomal chromosomes, as well as chromosome X, with 42 microsatellite markers and 56 endometrial cancers. The most frequent loss of heterozygosity (LOH) was observed on the long arm of chromosome 10 (14 of 30, 47%), which was commonly detected in grade 1 cancer. We constructed a detailed deletion map and defined two commonly deleted regions in 10q25-q26; one was the 8 cM region between D10S209 and D10S216, the other was the 12 cM region between D10S217 and D10S590. Replication errors at two or more loci were observed in 24 of 56 tumours (43%), suggesting that disruption of the DNA mismatch repair system also plays an important role in the course of endometrial carcinogenesis.

Adenocarcinoma, Clear Cell↗