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Biomedical subjects

Nobuo Yaegashi

Publications and source records attributed to Nobuo Yaegashi.

At least 55 records · Page 3Linked to original sources

Gastrointestinal immunophenotype in adenocarcinomas of the uterine cervix and related glandular lesions: a possible link between lobular endocervical glandular hyperplasia/pyloric gland metaplasia and 'adenoma malignum'.

Gastrointestinal phenotype in cervical adenocarcinomas was examined by immunohistochemistry and correlated with morphologic features. Antibody panels included anti-MUC2, MUC6, CD10, chromogranin A (CGA) and HIK1083. In addition, expression of p16INK4, a cyclin-dependent kinase inhibitor which is expressed in a variety of high-risk HPV-related conditions, was studied. A total of 94 invasive adenocarcinomas including 20 minimal deviation adenocarcinomas (MDAs) and 72 adenocarcinomas in situ (AIS) were examined. MDAs were most frequently positive for HIK1083 and/or MUC6, two representative gastric markers, with a rate of 95%, followed by intestinal-type adenocarcinomas (IAs) with a rate of 85% whereas only 27% of 56 usual endocervical-type adenocarcinomas (UEAs) were positive. MUC2, a goblet cell marker, was positive in 85% and 25% of IAs and MDAs, respectively, while in only 14% of UEAs. CD10 was positive in 15% of IAs, indicating incomplete intestinal differentiation without a brush border in most of the cases. CGA-positive cells were frequently seen in MDAs and IAs with rates of 60% and 62%, respectively. Nuclear and cytoplasmic p16INK4 positivity was identified in 93% of UEAs, whereas 30% of MDAs were positive for p16INK4. Results in AISs were comparable to their invasive counterparts, but morphologically usual-type AISs identified in eight cases of MDA were frequently positive for HIK1083 (75%) and MUC6 (63%), and p16INK4. Of note was the existence of lobular endocervical glandular hyperplasia (LEGH) with atypical features including cytologic abnormalities, and/or papillary projection, which were identified in this study in pure form (n=3) or in association with MDAs (n=6), but not in cases of other types of adenocarcinomas. These observations indicate that gastrointestinal phenotype is frequently expressed in MDAs and IAs, and there seems to be a possible link between MDA, and LEGH and morphologically usual-type AIS with gastric immunophenotype in histogenesis. Frequent absence of p16INK4 expression in MDAs suggests a possibility that high-risk HPV does not play a crucial role in development of MDAs, in contrast to the majority of endocervical adenocarcinomas. p16INK4 immunohistochemistry appears to be a promising diagnostic tool, but pathologists should be aware of frequent negative staining in MDAs, which can be a source of erroneous diagnosis.

Adenocarcinoma↗

Small cell neuroendocrine carcinomas of the uterine cervix: a histological, immunohistochemical, and molecular genetic study.

Small cell carcinomas of the uterine cervix are rare tumors with an aggressive behavior. Although these tumors can exhibit neuroendocrine differentiation, the criteria for neuroendocrine differentiation are subjective and not well defined. In this study, the authors tentatively defined small cell neuroendocrine carcinoma (SCNEC) as a tumor composed of small cells with at least two of the following: argyrophilic cytoplasm, chromogranin A immunoreactivity, and synaptophysin immunoreactivity. We found 10 cases fulfilling these requirements. Five of the 10 tumors were composed mainly of small ("oat") cells and 5 of mainly larger "intermediate" cells. The majority of both subtypes showed an insular pattern. Three of the 10 SCNECs were pure, whereas the other seven were mixed with adenocarcinoma and/or squamous cell carcinoma or cervical intraepithelial neoplasia. In addition to the definitional markers noted earlier, the tumors were immunoreactive for serotonin (6 cases), somatostatin, gastrin, glucagon, and pancreatic polypeptide. No tumors were immunoreactive for cytokeratin 20. Human papillomavirus (HPV)-18 was detected in all of the pure tumors and both the SCNEC and adenocarcinomatous components in four of the mixed tumors. No other types of HPV were detected. The tumors showed a relatively low frequency of loss of heterozygosity for representative tumor suppressor gene sites; p53 mutations were found in only one case.

Adult↗

Promoter methylation status and expression of TMS1 gene in human epithelial ovarian cancer.

Gene silencing associated with aberrant DNA methylation of promoter CpG islands is one mechanism through which tumor suppressor genes are inactivated in human cancers. TMS1 (target of methylation-induced silencing) is a CpG island-associated gene that functions in the regulation of apoptosis. In this study, we examined the DNA methylation status of the TMS1 promoter in ovarian cancer cell lines and tissues by methylation-specific PCR (MSP) and its mRNA expression by reverse transcription and quantitative PCR. Aberrant methylation of TMS1 was present in 7/12 ovarian cancer cell lines and 8/20 primary ovarian cancer tissues. The median value of relative TMS1 gene expression in cancers with methylation (0.15) was significantly lower than that in cancers without methylation (13.9) (P < 0.001). The expression of the TMS1 gene was relatively high (48.5) in the normal ovarian cDNA library. TMS1 gene expression was restored by treatment with the demethylating agent 5-aza-2'-deoxycitidine in the OV90 cell line, which lacks the TMS1 transcript. Our results suggest that aberrant methylation of TMS1 may play a role in the pathogenesis of ovarian cancer.

CARD Signaling Adaptor Proteins↗

Use of Mammalian eggs for assessment of human sperm function: molecular and cellular analyses of fertilization by intracytoplasmic sperm injection.

PROBLEMS: Intracytoplasmic sperm injection (ICSI ) has been described as the 'cure' for male sterility because a single sperm can now be directly introduced into an egg with some chance of pregnancy. While ICSI has revolutionized the practice of assisted reproductive techniques (ART), there are few molecular and cellular studies about its safety and efficacy. Even by using ICSI, fertilization in humans succeeds only if the sperm effectively accomplishes a number of tasks including 'post-ICSI events' in fertilization. To assess the function of human sperm after ICSI, we used heterologous ICSI with human sperm into animal eggs. Egg activation, sperm decondensation and sperm centorosomal function were examined in sperm from fertile men and infertile patients. METHODS: Sperm from fertile men and infertile patients were injected into hamster, rabbit and bovine eggs by Piezo micromanipulator, and studied in decondensation of sperm nuclei, egg activation and microtubule organization. RESULTS: Decondensation human sperm head following ICSI into hamster eggs occurred initially form basal lesion, and apical portion of sperm nuclei which is surrounded by acrosome and perinuclear theca, still condensed in early pronuclear stage. Radial array of microtubules from sperm centrosome 'sperm aster' which is essential for pronuclear movement was observed in 30% rabbit eggs following ICSI with human sperm. By heterologous ICSI system with fertile human sperm and bovine eggs, 83.3% of eggs was activated and 60% eggs had sperm aster, indicating that bovine Piezo ICSI system is appropriate for assessing human sperm oocyte activation ability and human sperm centrosomal function. Oocyte activation and sperm centrosomal function were significantly low in sperm from men with globozoospermia and men with dysplasia of fibrous sheath. CONCLUSION: These assays indicate differences of the process of fertilization between in vitro fertilization and ICSI, and reflect the human sperm function especially for the 'post-ICSI events' in fertilization. More molecular and cellular analyses in fertilization by ICSI are needed for improvement of ART.

Acrosome↗

Isolated torsion of the distal part of the fallopian tube in a premenarcheal 12 year old girl: a case report.

Isolated torsion of the fallopian tube in premenarcheal girls is very rare. However, correct diagnosis and treatment are needed in order to optimize salvage of fallopian tube. Here, we report a case of fallopian tube torsion in a premenarcheal girl. A 12-year-old premenarcheal girl was admitted with a rapid history of colicky lower abdominal pain. MR image demonstrated normal ovaries and a large spherical cystic tumor with hemorrhage-like contents. The differential diagnosis included torsion of a para-ovarian cyst or hydrosalpinx, hemorrhage within a non-communicating uterine horn or a pelvic hemorrhage of unknown origin. Laparoscopic inspection/operation was performed. The distal portion of the left fallopian tube was swollen with two twists evident in the middle portion. The distal portion of the left fallopian tube was laparoscopically removed with the aid of a YAG laser. The mechanisms underlying disorders of the left fallopian tube are not well understood. However, some intrinsic/extrinsic causative factors are discussed. Although torsion of the fallopian tube occurs rarely and exhibits variable clinical features, the diagnosis should be considered in all young girls presenting with sudden colicky abdominal pain. Laparoscopic inspection/surgery appears to be the most suitable management.

Abdominal Pain↗

Cervical cytologic examination during physical checkup of pregnant women: cervical cancer screening in women under the age of thirty.

Recently, the Ministry of Health, Labor and Welfare proposed that cervical cancer screening should be conducted for women aged 20 to 29 years old in Japan. However, there are insufficient data available in Japan concerning the screening conducted for women under the age of 30. Therefore, we made a survey of the results of cervical cytologic examination for pregnant women. 28,616 pregnant women were examined as subjects of a study group. A group of 108,289 women, subjected to group screening for cervical cancer in Miyagi Prefecture, were studied as a control group. The rate of subjects who required close examination in the pregnant women's group was significantly higher than that in the mass screening group (1.12% vs. 0.84%). The rate of close examination was significantly higher in the women 19 years old or younger compared to those in the age group of 25 to 39 years old. The rate was also significantly higher in women aged 20 to 24 years old than those who are 25 to 34 years old. Of the 321 subjects who required close examination, 34 cases underwent treatment, and 17 cases were under age 30. Moreover, all three cases of microinvasive and/or invasive carcinoma were under the age of 30 years (23, 23, 27 years old, respectively). Our results suggest that screening for cervical cancer in pregnancy is a useful means to find cervical neoplasia in young women and is effective in reducing the cervical cancer morbidity rate.

Adult↗

Retrospective analysis of concurrent chemoradiation with the combination of bleomycin, ifosfamide and cisplatin (BIP) for uterine cervical cancer.

Combination chemotherapy consisting of bleomycin, ifosfamide, and ciplatin (BIP) is recognized as one of the most effective chemotherapies for uterine cervical cancer. However, there have been no reports that evaluate concurrent use of radiation with BIP. The objective of this study was to evaluate the toxicity and response of the combination of BIP concurrent with radiation in patients with squamous cell carcinoma of the uterine cervix. Eligibility criteria included patients who underwent radical hysterectomy (Type III hysterectomy) as a primary treatment and revealed lymph node metastases or deep myometrial invasion (stage IB and IIA) and patients who were previously untreated (stage IIB-IV). All of the patients had biopsy-proven squamous cell carcinoma of the uterine cervix. The patients received three courses of BIP chemoradiation, and the response and toxicity were evaluated. From January 2000 to December 2003, 30 patients met study eligibility criteria. All but three patients completed 3 courses of planned chemotherapy. The frequency of severe (grade 3 and 4) toxicity was as follows: anemia, 46.7%; neutrocytopenia, 73.3%; thrombocytopenia, 16.7%; and nausea and vomiting, 23.3%. Among 30 patients, 22 cases were evaluated for response. Complete response was achieved in 16 (72.7%) of patients, with a response rate of 90.9%. In conclusion, BIP chemoradiation seems to be superior to previously reported chemoradiation regimens, and has a potential as an optimal combination chemotherapy concurrent with radiation.

Adult↗

Ectopic chromosome around centrosome in metaphase cells as a marker of high-risk human papillomavirus-associated cervical intraepithelial neoplasias.

This report describes the appearance of ectopic chromosome around centrosome (ECAC) in metaphase cell nuclei of high-risk HPV-associated cervical neoplasms. ECAC are clearly visible on HE-stained sections as a tiny (approx. 0.7 micro), round, dark structure or an aggregate of filamentous chromosome, often symmetrical at bilateral centrosomes. They appear in CINs from an early stage (CIN I), with the highest incidence in HPV16-associated CIN II-III (75%), and are less common in HPV-related invasive carcinomas (21%) and in lesions associated with high-risk HPV types other than 16. Rates for ECAC-positive nuclei in metaphase preparations (ECAC rate) for each lesion ranged 3.6-30%, the average being 14.5%. ECAC appeared very rarely in CINs associated with intermediate-risk HPVs and was never encountered in HPV6/11-induced condylomas or HPV-unrelated neoplasms in other organs. ECAC may be morphologic evidence of HPV-induced chromosomal instability working as a background mechanism in cervical carcinogenesis and also a useful marker for the histopathologic differentiation of high-risk CINs.

Aneuploidy↗

IgG antibodies to human papillomavirus 16, 52, 58, and 6 L1 capsids: case-control study of cervical intraepithelial neoplasia in Japan.

In Japan, human papillomavirus (HPV) 16, 52, and 58 are most commonly associated with cervical intraepithelial neoplasia (CIN). By contrast, HPV6 is primarily associated with genital warts. This study was designed to evaluate the association between IgG antibody responses to common HPVs and the risk of CIN development within a Japanese population. CIN cases (n = 141) and controls (n = 109) were tested for cervical HPV DNA and serum IgG antibodies to L1 capsids of HPV16, 52, 58, and 6. Seropositivity to HPV16, 52, and 58 L1 capsids was significantly higher in CIN cases than in controls: 27%, 21%, and 31% versus 16%, 11%, and 11%, respectively (P < 0.05). HPV6 L1 seropositivity was not significantly associated with CIN lesions (P = 0.11). Presence of viral DNA for either HPV16, 52, or 58 correlated with a significant antibody response against the homologous L1 capsids but not heterologous L1 capsids. Furthermore, seropositivity to multiple types of HPV16, 52, and 58 was more strongly associated with an increased risk of CIN development than seropositivity to a single type (P for trend <0.001). These findings indicate that IgG antibodies to L1 capsids of HPV16, 52, and 58 represent an increased risk of CIN development, with antibodies to multiple types being indicative of a further increase in risk. The presence of CIN lesions in women with seropositivity to multiple types suggests that viral exposure to a given type may not be protective against infections by other types and subsequent CIN development.

Adult↗

Immunohistochemical localization of steroidogenic enzymes in human follicle following xenotransplantation of the human ovarian cortex into NOD-SCID mice.

There have been reports of successful follicular growth following xenogenic transplantation of the human ovarian cortex into immunodeficient mice. In this study, we examined the immunohistochemical expression and localization of steroidogenic enzymes in the graft of nonpathological human ovary following xenogenic transplantation into nonobese diabetic severe combined immune deficient (NOD-SCID) mice. We studied human follicles following xenotransplantation into NOD-SCID mice using immunohistochemistry antibodies against the cell proliferation marker (Ki 67), steroidogenic enzymes P450 cholesterol side chain cleavage (P450 scc), 3beta-hydroxysteroid dehydrogenase (3beta-HSD), cytochrome P450 17alpha hydroxylase (P450 c17), cytochrome P450 aromatase (P450 arom), androgen receptor (AR), estrogen receptor (ER), and Ad4-binding protein (Ad4BP), a transcription factor for all steroidogenic P450 genes. In the pre-antral follicles of these grafts, Ki 67 and Ad4BP were detected in both the theca and granulosa cell layer. P450 scc, P450 c17, 3beta-HSD, and AR were present in only the theca cell layer, observations of which were consistent with the findings of nonpathological human ovarian cortex. P450 arom and ER were not detected in these grafts, however, and these follicles did not possess any specific feature of a dominant follicle. These findings suggest that the expression of steroidogenic enzymes in human follicles following xenogenic transplantation into NOD-SCID mice is similar to that of nonpathological human ovaries. However, these follicles do not possess any features of dominant follicles, which are known to develop into the corpus luteum.

Animals↗

Prognostic significance of second-look laparotomy for surgically confirmed early-stage epithelial ovarian cancer: a multicenter retrospective study.

BACKGROUND: In the present study, we conducted a multicenter retrospective analysis to elucidate the prognostic significance of second-look laparotomy (SLL) in early-stage epithelial ovarian cancer that was confirmed by complete surgical exploration. METHODS: In July 2001, 12 Japanese institutions received questionnaires regarding patients with early-stage epithelial ovarian cancer and SLL. Eligibility criteria included patients with stage I or II epithelial ovarian cancer who were surgically diagnosed between January 1988 and December 1997. Data were collected regarding age, performance status, tumor histologic subtype, stage, preoperative carbohydrate antigen (CA) 125 level, results of SLL if performed, recurrence, disease-free survival, and overall survival. Survival analyses and comparisons were performed by univariate methods. RESULTS: There were 87 patients who met the eligibility criteria. There were no significant differences in the backgrounds of patients who had had SLL ( n = 30) and the non-SLL group ( n = 57). Of the 30 SLL-group patients, 28 had negative SLL findings and 2 had positive findings. Six and 5 patients in the SLL group and the non-SLL group, respectively, had recurrence ( P = 0.177), and 4 patients in the SLL group had a recurrence after "negative" SLL findings. There was no significant difference between the two groups for either overall ( P = 0.73) or disease-free survival ( P = 0.273). On univariate analysis, only clear-cell histology was associated with a poor prognosis in early-stage epithelial ovarian cancer ( P = 0.031). CONCLUSION: SLL is not beneficial for early-stage epithelial ovarian cancer. More favorable outcomes will be achieved for early-stage patients with the improvement of treatment for clear-cell adenocarcinoma.

Adult↗

Measles infection in pregnancy.

OBJECTIVES: Measles during pregnancy has deleterious effects on both the perinatal outcome and the mother. However, in-depth knowledge about gestational measles is lacking. The objectives of this study were to describe the clinical course of eight cases of gestational measles and to study the effect of measles and pregnancy on each other. METHODS: From late 2000 to early 2001, we experienced a measles outbreak with eight infected pregnant women. The clinical course of each case is described in detail. RESULT: Three of the four cases before 24 weeks of gestation ended in spontaneous abortion or stillbirth. The clinical course of the three abortions and stillbirth were singular because of the sudden onset of the abortion and the spontaneous pregnancy termination. In contrast, the four pregnancies after 25 weeks of gestation ended in live-term delivery and two out of the four neonates were diagnosed with congenital measles. There was no maternal death, instead two pneumonia cases and one hemorrhagic shock case. CONCLUSIONS: Gestational measles may potentially damage the fetus and is one of the serious complications that can occur during pregnancy.

Abortion, Spontaneous↗

Establishment of multifunctional monoclonal antibody to the nonstructural protein, NS1, of human parvovirus B19.

OBJECTIVES: NS1 expression of human parvovirus B19 is a critical event in B19 pathogenesis. However, the mechanisms of NS1-induced cytotoxicity in B19 infection have yet to be clarified mainly because of the absence of multifunctional monoclonal antibodies (Mab) against NS1. The purpose of this study was to establish such Mab, which function in immunoprecipitation assays, immunoblotting, indirect immunofluorescence, and immunohistochemical staining. METHODS: Balb/c mice were immunized with the recombinant NS1 protein and hybridoma cell lines producing Mab against the NS1 protein were screened by ELISA, immunoprecipitation, immunoblotting, and indirect immunofluorescence staining. The Mab were used for immunohistochemical staining of formalin-fixed tissues from an intrauterine B19 infected fetus. RESULTS: ParC-NS1, the monoclonal antibody against the NS1 protein, worked in all tested screening methods. ParC-NS1 could also detect NS1 protein expressed in clinical tissue specimens. CONCLUSIONS: The ParC-Ns1 monoclonal antibody was specific against the NS1 protein. In addition, NS1 protein expression was successfully identified in human tissues. These data indicated that this monoclonal antibody should be a useful tool to study the kinetics and sites of NS1 expression and NS1-induced cytotoxicity in B19 infection.

Animals↗

Total laparoscopic surgery of cystic adenomyoma under hydroultrasonographic monitoring.

A 19-year-old-woman had a cystic adenomyoma located within the myometrium. She complained of severe dysmenorrhea. Gonadotropin-releasing hormone agonist therapy was administered, but her dysmenorrhea was more pronounced than before treatment. Therefore, total laparoscopic resection of the lesion was performed. The external appearance of the patient's uterus was almost normal. A hydroultrasonographic monitoring method was devised (transvaginal ultrasonography with peritoneal hydration of physiologic saline) that proved useful in locating the adenomyoma. The patient's dysmenorrhea disappeared postoperatively.

Adenomyoma↗

Increased production of tumor necrosis factor-alpha by peritoneal fluid mononuclear cells induced by 60-kDa heat shock protein in women with minimal to mild endometriosis.

PROBLEM: We sought to examine the role of Hsp60, a 60-kDa stress-responsive protein (hsp60) with potent immunostimulatory properties, in the pathophysiology of endometriosis. We investigated the response of peritoneal fluid mononuclear cells (PFMCs) to hsp60 to identify differences in PFMCs between women with and without endometriosis. METHOD OF STUDY: PFMCs from women with or without endometriosis were incubated with hsp60 in vitro. The release of tumor necrosis factor (TNF)-alpha was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The rapid secretion of TNF-alpha was observed following the exposure of PFMCs to hsp60. PFMCs from women with minimal to mild endometriosis produced greater amounts of TNF-alpha in response to hsp60 stimulation than levels seen in cells from women without endometriosis. CONCLUSION: Hsp60 may play a role in the activation of peritoneal immunity in patients with minimal to mild endometriosis.

Adult↗