Biomedical subjects

Kunihiro Okamura

Publications and source records attributed to Kunihiro Okamura.

At least 55 records · Page 3Linked to original sources

PubMed2004

Cyclooxygenase-2 expression in deep endometriosis and matched eutopic endometrium.

OBJECTIVE: To identify any relationship between cyclooxygenase-2 expression and the intensity of severe, endometriosis-related dysmenorrhea. DESIGN: Prospective study. SETTING: University hospital. PATIENT(S): Patients with deep endometriosis. INTERVENTION(S): During surgery, paired samples of tissue representing deep endometriosis and eutopic endometrium were obtained from 46 patients. Control endometrial tissue samples were obtained from 34 fertile women who underwent laparoscopic tubal ligation or reversal of tubal sterilization. Pain assessment for dysmenorrhea was done with a 10-point linear analogue scale. MAIN OUTCOME MEASURE(S): The percentage of surface immunostained for Cox-2 was determined by an immunohistochemical technique. Relationships between pain score for dysmenorrhea and Cox-2 expression were analyzed. RESULT(S): Cox-2 expression was significantly higher in eutopic endometrial stromal cells from patients with deep endometriosis than in stroma from controls during the early, mid, and late secretory phases. In endometriosis patients, Cox-2 expression in eutopic endometrial stromal cells was significantly higher in women with more severe dysmenorrhea (pain score > or =7 vs. <7) during early and mid secretory phases. CONCLUSION(S): Elevated Cox-2 expression in stromal cells in eutopic endometrium from patients with deep endometriosis may play a role in severe, endometriosis-related dysmenorrhea.

Adult↗

PubMed2004

Cyclooxygenase-2 selective inhibitor prevents implantation of eutopic endometrium to ectopic sites in rats.

OBJECTIVE: To evaluate Cox-2 inhibition on surgically induced endometriosis in rats. DESIGN: Prospective, randomized study SETTING: Academic facility. ANIMAL(S): Seventy adult female Sprague-Dawley rats. INTERVENTION(S): Uterine fragments were implanted into abdominal peritoneum with suture (site A), and/or into the pelvic cavity without suture (site B). Oral gavage of Cox-2 inhibitor (5 mg/kg/day, twice/day) was started 4 weeks postimplantation (protocol-1), after implantation (protocol-2), or beforehand (protocol-3). Controls received vehicle. Immunohistochemistry evaluated Cox-2 expression after treatment. MAIN OUTCOME MEASUREMENT(S): Presence and size of ectopic implants after treatment. RESULT(S): Protocol-1: After 4 weeks' treatment, size of ectopic implants (site A) was significantly reduced compared with pretreatment size. After 8 weeks' treatment, no ectopic implants were detected in 2 (40%, site A) and 3 (60%, site B) rats. Protocol-2: After 2 weeks' treatment, no ectopic implants were detected in 3 (50%, site A) and 2 (33%, site B) rats. After 4 weeks' treatment, no ectopic implants were detected in 3 (50%, site A) and 3 (50%, site B) rats. Protocol-3: After 2 or 4 weeks' vehicle-only treatment, ectopic implants were in all rats (site B). CONCLUSION(S): Cox-2 selective inhibition was effective in a rat model of endometriosis, particularly in prevention of ectopic implants.

Animals↗

PubMed2004

A case of primary mucosa-associated lymphoid tissue lymphoma of the vagina.

We report the first case of primary mucosa-associated lymphoid tissue (MALT) lymphoma of the vagina, the diagnosis of which is supported by genetic and immunophenotypic studies. A 65-year-old, para 2 woman presented to our hospital in July 1997 with a history of prolonged vaginal discharge. Although cytologic examination suggested possible malignancy, a biopsy of the vaginal wall was diagnosed as chronic inflammation. In June 2000, she underwent gynecologic examination because of anuria. Excisional biopsy revealed subepithelial infiltration of atypical lymphoid cells that stained for CD20, CD79a, and BCL-2; stained weakly for IgM; and did not stain for CD3, CD5, CD7, CD10, CD56, CD23, and IgD, suggesting marginal zone B-cell lineage. Monoclonality was detected by Southern blot analysis, and this patient was finally diagnosed as having primary MALT lymphoma of the vagina. She received 3 cycles of chemotherapy (THP-COP) and concurrent radiation to the whole pelvis. The patient is alive and well 40 months after treatment. Because the vagina is one of the mucosa-associated tissues, MALT lymphoma, though rare, must be included in the differential diagnosis of the vaginal neoplasms.

Aged↗

PubMed2004

Sentinel lymph node detection in early cervical cancer with combination 99mTc phytate and patent blue.

OBJECTIVE: The purpose of this study was to examine sentinel lymph node (SLN) detection in patients with early stage cervical cancer using (99m)Tc phytate and patent blue dye and to compare our method with published findings utilizing other radioisotopic tracers. PATIENTS AND METHODS: A total of 20 consecutive patients with cervical cancer scheduled for radical hysterectomy and total pelvic lymphadenectomy at our hospital underwent SLN detection study. The day before surgery, lymphoscintigraphy was performed with injection of 99m-technetium ((99m)Tc)-labeled phytate into the uterine cervix. At surgery, patients underwent lymphatic mapping with a gamma-detecting probe and patent blue injected into the same points as the phytate solution. RESULTS: At least one positive node was detected in 18 patients (90%). A total of 46 sentinel nodes were detected (mean, 2.3; range, 1-5). Most sentinel nodes were in one of the following sites: external iliac (21 nodes), obturator (15 nodes), and parametrial (7 nodes). Eleven (24%) sentinel nodes were detected only through radioactivity and two (4%) were detected only with blue dye. The sensitivity, specificity, and negative predictive value for SLN detection were all 100%. Nine published studies involving 295 patients had a summarized detection rate of 85%. Summarized sensitivity, specificity, and negative predictive value were 93%, 100%, and 99%, respectively. CONCLUSION: Combination of (99m)Tc phytate and patent blue is effective in SLN detection in early stage cervical cancer.

Adult↗

PubMed2004

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↗

PubMed2004

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↗

PubMed2004

The Tohoku Study of Child Development: A cohort study of effects of perinatal exposures to methylmercury and environmentally persistent organic pollutants on neurobehavioral development in Japanese children.

Several birth cohort studies have shown adverse effects of perinatal exposures to methylmercury (MeHg) and environmentally persistent organic pollutants (POPs). These chemicals are ingested mainly through fish consumption, but little is known about the hazardous effects in Japanese, whose fish consumption is high. The present study, the Tohoku Study of Child Development, was designed to examine the effects of perinatal exposures to MeHg, polychlorinated biphenyls (PCB), dioxins, pesticides, and other chemicals in Japanese children. Six hundred eighty-seven pregnant women were participated in this study with their written informed consent. Maternal peripheral blood, cord blood, cord tissue, placenta, and breast milk samples were collected for chemical analysis. Maternal hair was also taken for MeHg analysis. Infants born at full term were assessed by neurobehavioral tests: the Brazelton Neonatal Behavioral Assessment Scale at three days old, the Kyoto Scale of Psychological Development and the Bayley Scales of Infant Development at 7 and 18 months old, and the Fagan Test of Infant Intelligence at 7 months old. The children will be continuously followed up to ages 6-7 years. Maternal food intake frequency, maternal IQ, socioeconomic status, and home environment were assessed as covariates. The results of this cohort study will allow us to evaluate associations between the neurobehavioral development of children and perinatal exposures to MeHg and environmentally POPs in Japan.

Animals↗

PubMed2004

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↗

PubMed2004

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↗

PubMed2004

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↗

PubMed2003

CpG dinucleotide methylation patterns in the human androgen receptor gene and X-chromosome inactivation in peripheral blood leukocytes of phenotypically normal women.

To evaluate methylation patterns in CpG dinucleotides (CpGs) of the human androgen receptor gene ( HUMARA) and X-chromosome inactivation (XCI) status in phenotypically normal women in a general population, bisulfite genomic sequencing and methylation-specific PCR of genomic DNA extracted from peripheral blood samples of 124 phenotypically normal women were examined. CpGs methylation patterns were based on bisulfite genomic sequencing of the region containing nine CpGs in the HUMARA exon 1. The results of methylation status in CpGs from 43 independent colonies of 14 women revealed that not all CpGs were methylated even in highly methylated HUMARA alleles, and that the methylation status in CpGs varied between clones, by the position of CpGs methylation and in each subject. Evaluation of XCI was based on the method of an HUMARA (CAG)n polymorphism assay after bisulfite modification of DNA samples. The HUMARA allele size ratios of the women (82 heterozygotes) varied over a wide range and the distribution patterns of the ratios approached a 'normal distribution'. Since excessive skewing of XCI was observed in 11-12% of women, female carriers of an X-linked hereditary disease manifest its clinical symptoms or signs possibly in maximum 5-6%.

Adult↗

PubMed2003

Fractal and periodic heart rate dynamics in fetal sheep: comparison of conventional and new measures based on fractal analysis.

The physiological significance of spectral and fractal components of spontaneous heart rate (HR) variability in the fetus remains unclear. To examine the relationship between circadian rhythms in different measures of HR variability, R-R interval time series obtained by fetal ECGs were recorded continuously over 24 h in five pregnant sheep at 116-125 days gestation. Conventional measures of short-term (STV) and long-term variability (LTV), low-frequency (LF; 0.025-0.15 cycles/beat) and high-frequency (HF; 0.2-0.5 cycles/beat) spectral powers, the LF-to-HF ratio, and fractal dimension values were calculated from 24-h ECG recordings and quantified every 60 min. STV, LTV, and LF and HF spectral powers were minimal during the day but increased significantly to their highest values at night. We found a significant positive correlation between these measures, whereas the cosinor method showed significant similarity between their circadian rhythm patterns. Fetal R-R intervals also exhibited fractal structures. Fetal HR variability had a fractal structure, which was similar between day and night. These results suggested that the circadian rhythms exhibited by STV and LTV during the day were mainly due to changes in frequency components rather than to fractal components of fetal HR fluctuation.

Animals↗

PubMed2003

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↗

PubMed2003

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↗

PubMed2003

Analysis of the clonality of ectopic glands in peritoneal endometriosis using laser microdissection.

OBJECTIVE: To investigate the clonality of ectopic gland cells in peritoneal endometriosis. DESIGN: Prospective study. University hospital. PATIENT(S): Seventeen women with surgically diagnosed endometriosis. INTERVENTION(S): Samples of peritoneal endometriotic lesions were obtained from patients during laparoscopic surgery. MAIN OUTCOME MEASURE(S): Clonality analysis used the laser microdissection technique, a phosphoglycerate kinase (PGK) gene polymorphism assay, and an androgen receptor (AR) gene polymorphism assay after digestion of the DNA with methylation-sensitive endonuclease. RESULT(S): Each ectopic gland of the peritoneal endometriotic lesion showed a monoclonal pattern in both the PGK gene and AR gene assays, but the methylation pattern of the PGK gene and/or AR gene was divergent among adjacent glands in the lesion. These data indicate that the peritoneal endometriotic lesions are multicellular in origin, although individual glands of the lesion are derived from single precursor cells. CONCLUSION(S): The colored peritoneal endometriotic lesion in the present study was multicellular in origin. Peritoneal endometriotic lesions may thus be initiated by transplantation of a cluster of eutopic endometrial tissues into the pelvis.

Clone Cells↗

PubMed2003

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↗

PubMed2003

Cul-de-sac packing with a metreurynter in gasless laparoscopic cystectomy during pregnancy.

Gasless laparoscopic cystectomy was performed for a woman in the fifteenth week of pregnancy. An ovarian cyst that had been sinking behind the uterus appeared spontaneously after ballooning the metreurynter in the pouch of Douglas. This allowed extraperitoneal cystectomy, and the patient's subsequent antenatal course was uneventful. Cul-de-sac packing with a metreurynter permits gentle and atraumatic manipulation against the pregnant uterus.

Adult↗

PubMed2003

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↗