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Biomedical subjects

Kunihiro Okamura

Publications and source records attributed to Kunihiro Okamura.

At least 19 recordsLinked to original sources
PubMed2007

Effects of photodynamic therapy using 5-aminolevulinic acid on cultured human adenomyosis-derived cells.

OBJECTIVE: To evaluate the potential of photodynamic therapy with aminolevulinic acid (ALA) on human adenomyosis-derived cells compared with endometrial stromal cells. DESIGN: In vitro study. SETTING: Department of Obstetrics and Gynecology, Tohoku University Hospital. PATIENT(S): Women with adenomyosis attending the University hospital. INTERVENTION(S): Photodynamic treatment. MAIN OUTCOME MEASURE(S): Cell survival rates. RESULT(S): Treatment with both ALA and irradiation caused significantly decreased survival of cells derived from human adenomyosis compared with ALA or irradiation alone. The combination of irradiation and ALA led to 79.3%, 68.0%, and 59.5% cell survival at 1.6, 4, and 8 J/cm2, respectively, whereas ALA and irradiation alone caused 92.8% and 97% survival, respectively. CONCLUSION(S): Photodynamic therapy using ALA caused extensive death of cells derived from human adenomyosis. Photodynamic treatment using ALA may be a new treatment for patients with adenomyosis uteri in the future.

Adult↗
PubMed2006

A case surviving for over a year of renal tubular dysgenesis with compound heterozygous angiotensinogen gene mutations.

Renal tubular dysgenesis (RTD) is a developmental abnormality of the renal proximal tubules found in patients with Potter syndrome. We report a female newborn with RTD who has survived for more than 18 months. Infusions of fresh frozen plasma (FFP) in the early neonatal period were effective in raising and maintaining her blood pressure. Peritoneal dialysis was required until the appearance of spontaneous urination at 29 days after birth. Histopathological examinations of the kidney revealed dilated renal tubular lumina and foamy columnar epithelial cells in the renal tubules. Endocrinological studies showed a discrepancy between low plasma renin activity (<0.1 ng/ml/hr) and high active renin concentration (135,000 pg/ml), suggesting an aberration in the renin substrate, angiotensinogen. Direct sequencing analysis revealed two novel mutations in the coding region of the angiotensinogen gene (AGT): a nonsense mutation in exon 2 (c.604C > T) and a frameshift deletion at nucleotide 1290 in exon 5 (c.1290delT). The mutations were in the compound heterozygous state, because each parent had each mutation. These findings suggest that angiotensinogen deficiency is one of the causes of RTD. A treatment of the condition with FFP may help to promote long survival.

Angiotensinogen↗
PubMed2006

Successful strategy for the hysteroscopic myomectomy of a submucous myoma arising from the uterine fundus.

OBJECTIVE: To introduce a technique for hysteroscopic resection of submucous myoma arising from the uterine fundus. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 43-year-old nulliparous Japanese woman. INTERVENTION(S): An original combination technique of hysteroresectoscopy using circumferential myoma scraping, central vaporization, and intraoperative injection of prostaglandin F2alpha. MAIN OUTCOME MEASURE(S): Evaluation of clinical symptoms and imaging diagnosis. RESULT(S): Resection of a 40-mm fundal myoma was performed hysteroscopically, and the menorrhagia of the patient was remedied by the operation. CONCLUSION(S): Although large sessile fundal myomas are difficult to resect by hysteroscopic myomectomy, our original strategy may allow safe and certain surgery in such cases.

Adult↗
PubMed2006

Progesterone receptor isoforms as a prognostic marker in human endometrial carcinoma.

The possible role of specific progesterone receptor (PR) isoforms (PRA and PRB) as predictive factors in endometrial carcinoma is unclear. The present study was undertaken to evaluate the clinical significance of intratumoral PR isoform status in patients with endometrioid endometrial carcinoma. We studied 103 cases of endometrioid endometrial carcinoma using immunohistochemistry. We correlated the findings with various clinicopathological parameters of the patients. PRA and PRB immunoreactivity was detected in 51/103 (48.5%) and 79/103 (76.7%) of carcinoma cases, respectively. A significant positive correlation was detected between the status of PRB immunoreactivity and the amount of PRB mRNA by real-time reverse transcription-polymerase chain reaction (P = 0.012). PR isoform expression was significantly lower in the cases with higher histological grade (P = 0.0001 and P = 0.002, for PRA and PRB, respectively). Cases that were negative for either one or both PR isoforms were significantly associated with shorter disease-free and overall survival of the patients. The absence of either one or both of these two PR isoforms was detected in all nine patients who died (100.0%), whereas the absence of these immunoreactivities was detected only in 43 of 94 (45.7%) patients who had lived during the same period. In addition, multivariate analysis demonstrated that an absence of PRA immunoreactivity was an independent risk factor in disease-free survival of the patients (P = 0.0258). The results of our study demonstrated that loss or absence of PR isoform expression determined by immunohistochemistry could become an important prognostic indicator in patients with endometrioid endometrial carcinoma.

Adenocarcinoma↗
PubMed2006

A selective cyclooxygenase-2 inhibitor suppresses the growth of endometriosis xenografts via antiangiogenic activity in severe combined immunodeficiency mice.

OBJECTIVE: To investigate the effects of a selective cyclooxygenase (COX)-2 inhibitor on endometriosis xenografts in immunodeficient mice. DESIGN: Prospective placebo-controlled study. SETTING: An academic facility at a Japanese university graduate school of medicine. PATIENT(S): Eight human ovarian endometriomas from seven patients. ANIMAL(S): Twenty-three female severe combined immunodeficiency (SCID) mice. INTERVENTION(S): Human ovarian endometriomas were implanted into the peritonea of SCID mice. Vehicle alone or NS398 (a selective COX-2 inhibitor, 10 mg/kg of weight per day) were administered orally daily for 56 days after implantation. Mice were killed on the 56th day. MAIN OUTCOME MEASURE(S): Change in explants size and immunohistochemical analyses to evaluating the proliferation index, apoptosis index, microvessel density, and labeling index assessing vascular endothelial growth factor and COX-2 expression by the endometriotic lesion. RESULT(S): NS398 significantly decreased implant size in comparison to vehicle alone (NS398 [medians, with range in brackets]: 22.0% [19.0%-36.7%] vs. vehicle: 41.2% [31.0%-55.3%], P<.01). Microvessel density (85.3 per mm2 [53.9-157.0 per mm2] vs. 121.8 per mm2 [97.2-259.6 per mm2], P=.02) and the vascular endothelial growth factor (0.4 [0-1.1] vs. 0.6 [0.5-2.1], P=.03) and COX-2 (0.4 [0.4-0.5] vs. 0.6 [0.4-0.8], P=.03) labeling indices in stromal cells were significantly lower in the NS398 group than in the vehicle group. There were no differences in the proliferation or apoptosis indices between the two groups. CONCLUSION(S): Selective COX-2 inhibitors decreased the size of implants and effectively treated endometriosis.

Adult↗
PubMed2006

Peroxisome proliferator-activated receptor gamma and growth inhibition by its ligands in uterine endometrial carcinoma.

PURPOSE: In this study, we evaluated the correlation between endometrial carcinoma and peroxisome proliferator-activated receptor gamma (PPARgamma) expression and assessed whether PPARgamma ligands influence carcinoma growth. EXPERIMENTAL DESIGN: We examined the presence and cellular distribution of PPARgamma protein in 42 normal endometria, 32 endometria with hyperplasia, and 103 endometria with endometrial carcinoma by immunohistochemistry. We then compared PPARgamma mRNA expression in endometrial carcinoma with that in normal endometria using real-time reverse transcription-PCR. We subsequently confirmed expression of PPARgamma mRNA by real-time reverse transcription-PCR and PPARgamma protein by immunoblotting in endometrial carcinoma cell lines (Ishikawa, Sawano, and RL95-2 cells). We further examined the effects of PPARgamma agonist 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2), a naturally occurring PPARgamma ligand, to these endometrial carcinoma cell lines. We also examined the status of apoptosis and p21 mRNA expression of these endometrial carcinoma cell lines following addition of 15d-PGJ2. RESULTS: PPARgamma immunoreactivity was detected in 11 of 23 (48%) of proliferative-phase endometrium, 14 of 19 (74%) of secretory-phase endometrium, 27 of 32 (84%) of endometrial hyperplasia, and 67 of 103 (65%) of carcinoma cases. PPARgamma immunoreactivity was significantly lower in endometrial carcinoma than in secretory-phase endometrium (P = 0.012) and endometrial hyperplasia (P = 0.006). There was a significant positive association between the status of PPARgamma and p21 expression in endometrial carcinoma (P < 0.0001). There was a significant negative association between the body mass index and PPARgamma labeling index of carcinoma tissue in the patients with endometrial carcinoma (P < 0.0001). PPARgamma mRNA was expressed abundantly in normal endometria but not in endometrial carcinoma. We showed that PPARgamma agonist 15d-PGJ2 inhibited cell proliferation and induced p21 mRNA of endometrial carcinoma cell lines. CONCLUSION: We showed the expression of PPARgamma in human endometrial carcinoma and the effects of PPARgamma ligand in endometrial carcinoma cells. These findings suggest that a PPARgamma ligand, 15d-PGJ2, has antiproliferative activity against endometrial carcinoma.

Aged↗
PubMed2006

Fish consumption and time to pregnancy in Japanese women.

The work described in this paper examined the possible relationship between fish consumption and human fecundity among Japanese women using hair mercury level and time to pregnancy (TTP) as indicators of fish consumption and fecundity. We hypothesized that hair mercury concentrations reflect the level of fish consumption and, consequently, can also be taken to indicate the level of intake of organochlorine compounds (OCs) such as dioxins and polychlorinated biphenyls (PCBs) for which fish are the primary source, and which can disrupt normal human reproductive processes. TTP was obtained by a self-administered questionnaire from women who had been delivered of a baby at either of two hospitals in Sendai, Japan, during the period of January 2002-March 2004. Total mercury concentration in their hair (0-3cm from the scalp) was determined by cold vapor atomic absorption spectrometry. Of the 298 women approached, 193 (65%) reported their TTP. The subjects were classified into two groups according to their TTP: group 1, 0-12 months TTP; and Group 2, >12 months TTP. A step-down procedure backward binominal logistic regression analysis was performed by using age, BMI, parity, frequency of intercourse, life-style parameters (smoking, drinking and dietary habits) and hair mercury level of the female subjects and their partners as independent variables. Two separate analyses were performed by including/excluding information on the partners of the subjects. The analyses did not extract hair mercury concentration as significant indicating that fish consumption did not prolong TTP, which was not consistent with the results of our previous study, i.e., in that study frequent fish eaters showed prolonged TTP. Possible reasons of the negative result are discussed and it is suggested that the hair mercury levels in the present study were not an appropriate indicator of fish consumption of the subjects or of their exposure to OCs. Further study on the relationship between fish consumption (and, ultimately, of OCs intake) and fecundity with more appropriate indicators of fish consumption and/or fish-mediated pollutants intake are warranted to characterize the health risk posed by fish consumption.

Adult↗
PubMed2006

17Beta-hydroxysteroid dehydrogenases in human endometrium and its disorders.

In situ estrogen metabolism and synthesis have been considered to play a very important role in the development and progression of human endometrial carcinoma. 17Beta-hydroxysteroid dehydrogenases (17-HSDs) are enzymes involved in the formation of active sex steroids, including testosterone, estrone (E1) and estradiol (E2). Estrogens are interchanged by two enzymes, 17-HSD types 1 and 2, type 1 converts E1 to E2, and type 2 does reverse actions. 17-HSD type 5 catalyzes the reduction of androstenedione to testosterone. 17-HSD type 2 expression was decreased through normal endometrium, hyperplasia and carcinoma accordingly. There was a significant inverse correlation between intratumoral E2 concentration and the level of 17-HSD type 2 mRNA in endometrial carcinoma. 17-HSD type 5 expression was significantly increased through normal endometrium, hyperplasia and carcinoma accordingly. These results indicated that 17-HSD types 2 and 5 play an important role in the regulation of in situ estrogen production in endometrial carcinoma.

17-Hydroxysteroid Dehydrogenases↗
PubMed2006

Prolonged relaxant effects of vecuronium in patients with deliberate hypermagnesemia: time for caution in cesarean section.

We present two cases showing significantly prolonged action of vecuronium from magnesium treatment after general anesthesia for urgent cesarean section. The serum magnesium levels were maintained at a therapeutic range for severe eclampsia in one patient (5.6 mg.dl(-1)) and for tocolysis in another with placenta previa totalis (6.9 mg.dl(-1)). The obstetrics-specific emergency in each patient led us to proceed with general anesthesia but using reduced-dose vecuronium, which failed to prevent prolongation of the neuromuscular block. As a result, the patients received prolonged mechanical ventilation. Our cases underscore the need for anesthesiologists as well as obstetricians to be aware of the prolongation of the action of nondepolarizing muscle relaxants as a result of magnesium treatment.

Adult↗
PubMed2006

Measurement method for the fetal electrocardiogram.

A fetal electrocardiogram (ECG) provides clinically significant information concerning the electrophysiological states of a fetus. Since the first attempt by Cremer in 1906, for about 100 years nobody has been able to non-invasively extract the fetal ECG popularly used in clinical situations. The low amplitude of the fetal signals and the high background noise and the non-linearity of the ECG signals mainly have been interfering with the noninvasive extraction of the fetal ECG. The aim of this paper is to introduce a new nonlinear filtering method to extract the fetal electrocardiogram detected from the mother's abdominal wall. This method consists of two steps: The rough extraction step performed by blind source separation (BSS) with references and the precise extraction step with fast non-linear state space projection (FNSSP) based on a nonlinear state space projection (NSSP), which needs several complicated conditions or has limitations. So, it takes a lot of time to calculate. Our new method does not require such conditions, and it has about a thirty-fold speedup when compared with the previous method. Our new method has been successfully applied to on-line recordings with fetal components and will be useful for monitoring the fetal electrocardiogram in clinical applications.

Electrocardiography↗
PubMed2006

Fetal myocardial thickening measured by ultrasonic-based technique called 'phased-tracking method'.

OBJECTIVE: To evaluate fetal myocardial movement by using newly developed ultrasonic technique. METHODS: We analyzed 50 normal fetuses between 25 and 41 weeks' gestation for changes in thickness of fetal myocardium using the phased-tracking method, a technique with high vertical distance resolution and the potential to evaluate fine ventricular wall movements. We analyzed differences in the rate of change in ventricular wall thickness and in changes in the inner and outer wall layers with advancing gestation. We also analyzed myocardial thickening period and evaluated the ratio of increasing thickness period to stroke interval. RESULTS: Mean thickness changing rate was significantly higher in the right (1.18 +/- 0.34 m/s/m) than in the left ventricular wall (0.86 +/-0.31 m/s/m) (p < 0.001). Mean ratio of increasing thickness period to stroke interval was significantly higher in the right (0.57 +/- 0.064) than in the left ventricle (0.46 +/- 0.075) (p < 0.001), indicating that myocardial contraction in the fetal right ventricle predominates. The thickness-changing rate of the bilateral ventricular walls was positively and linearly correlated with gestational age. The myocardial-wall thickness-changing rate was higher in the outer layer than in the inner layer in late gestation. CONCLUSIONS: We conclude that measurement of the thickness-changing rate of fetal ventricular walls using the phased-tracking method might be useful for evaluation of fetal cardiac function.

Echocardiography↗
PubMed2006

Lactation and risk of endometrial cancer in Japan: a case-control study.

The incidence of endometrial cancer is rapidly increasing in Japan. Although the risk factors in European populations have been well described, there are few epidemiologic studies regarding risk factors for endometrial cancer in Japanese women. This hospital-based case-control study among Japanese women was carried out from 1998 to 2000. The cases were selected from women with endometrial cancer (n =155), and the controls selected from women attending the university gynecological outpatient clinic for cervical cancer screening (n = 96). Subjects were interviewed to ascertain breast feeding practices, contraceptive usage, as well as potential risk factors for endometrial cancer. We observed a lower risk of endometrial cancer associated with oral contraceptive (OC) and a higher risk associated with higher body mass index (BMI), and older ages at first and last delivery. Gravidity reduced odds ratio (OR) for endometrial cancer to 0.34 (95% confidence interval [CI] 0.13-0.92). Compared with parous women who had never breastfed, the multivariate OR for women with a history of breastfeeding was 0.37 (95% CI, 0.17-0.82). Additionally, a greater lapse of time since breastfeeding increased OR for endometrial cancer by over three times. In conclusion, the present study has indicated that breastfeeding reduces the risk of endometrial cancer in Japanese women.

Adult↗
PubMed2006

Appearance of abnormal electrocorticogram patterns during umbilical cord compression in sheep fetus.

A frequent cause of fetal acidemia, which sometimes results in hypoxic-ischemic encephalopathy, is umbilical cord compression associated with uterine contraction. Using a sheep model of fetal acidemia, we examined the changes in electrocorticogram (ECoG), carotid artery blood flow, arterial blood pressure and fetal heart rate during cord compression. A characteristic burst of ECoG spikes emerged during cord compression at fetal arterial pH 7.18 even before the pH went down to severe fetal acidemia (less than 7.10). The administration of a neuromuscular blocking agent to the fetus did not abolish the appearance of the spikes. These results suggest that cord compression may cause abnormal brain excitement even in the absence of severe fetal acidemia and that this abnormal excitement can lead to fetal brain dysfunction, if cord compression is repeated or prolonged.

Acidosis↗
PubMed2006

Clinical manifestations and outcomes of parvovirus B19 infection during pregnancy in Japan.

Parvovirus B19 is a small DNA virus. Infection with parvovirus B19 during pregnancy may cause serious complications in the fetus, including hydrops fetalis and fetal death. The purpose of the present study is to clarify the clinical manifestations and outcomes of parvovirus B19 infection during pregnancy. This prospective study enrolled 478 women with suspected B19 infections during pregnancy between 1999 and 2004. One hundred cases (21%) of B19 infection were detected in 478 pregnant women who had been exposed to B19. Serological infection was confirmed by measurement of B19-specific IgM and IgG in sera. Forty-nine cases reported maternal clinical symptoms and 51 cases were asymptomatic. Facial rash was the most common symptom, with 51% (25/49) of the symptomatic patients complaining of either a facial, body or limb rash. The most common infectious source was children living in the home. Overall, the incidence of adverse fetal effects (including hydrops fetalis and fetal death) related to intrauterine B19 infection was 7% (7/100), and all seven cases were exposed to B19 infection before 20 weeks of gestation. Although half of the cases with parvovirus B19 infections during pregnancy were asymptomatic, patients with adverse fetal effects tended to be symptomatic including rash and fever. These clinical data may supply useful information to produce clinical guidelines for managing B19 infection during pregnancy.

Abortion, Spontaneous↗
PubMed2006

Management of the pain associated with endometriosis: an update of the painful problems.

Endometriosis is a condition characterized by ectopic endometrial tissues located outside of the uterus, most commonly found on the pelvic peritoneum or ovary. Endometriosis, which occurs in 7-10% of women in the general population and 71-87% of women with chronic pelvic pain, is associated with dysmenorrhea, chronic pelvic pain, and infertility. There is considerable debate about the effectiveness of various interventions for endometriosis. This review discusses the benefits and drawbacks of pharmacologic and surgical treatments for the pain associated with endometriosis. Laparoscopic surgery has been demonstrated to relieve the pain associated with endometriosis. Hormonal therapies, such as gonadotropin-releasing hormone (GnRH) analogues or the weak androgen danazol, have also been effective at relieving the pain associated with endometriosis. Oral contraceptives appear to be as effective as GnRH analogues for pain relief. Although both surgical and pharmacologic treatments have been effective for relief of the pain associated with endometriosis, the recurrence rate remains significant. The management of pain associated with endometriosis has thus not been satisfied. Larger unified clinical trials are needed to evaluate the effectiveness of new treatments in managing the pain associated with endometriosis.

Clinical Trials as Topic↗
PubMed2006

Association of maternal smoking during pregnancy and infant neurobehavioral status.

The association of maternal smoking during pregnancy with neurobehavioral status was examined in 344 Japanese infants. Based on a questionnaire, their mothers were classified into three groups, Nonsmokers, Exsmokers, and Smokers. The Neonatal Behavioral Assessment Scale was administered three days after birth. Among the three groups, on the seven clusters and their 28 behavioral subscales there were no significant differences. The infants of Smokers had lower scores than those of Exsmokers and Nonsmokers on two behavioral items, general tone and peak of excitement. General tone remained significant after adjustment for covariates.

Adult↗
PubMed2005

14-3-3sigma in endometrial cancer--a possible prognostic marker in early-stage cancer.

PURPOSE: We examined expression of 14-3-3sigma, a regulator of cell proliferation, and evaluated its clinical significance in endometrioid endometrial carcinoma. EXPERIMENTAL DESIGN: One hundred three endometrioid endometrial adenocarcinoma cases were examined using immunohistochemistry with archival specimens. We correlated this finding with various clinicopathologic variables, including the status of estrogen receptor, progesterone receptor, and MIB-1 (Ki-57). RESULTS: 14-3-3sigma Immunoreactivity was detected in 78 of 103 (75.3%) of carcinoma cases. No statistically significant correlation was detected between status of 14-3-3sigma and any of clinicopathologic variables examined. There was, however, a statistically significant correlation between loss of 14-3-3sigma expression and adverse clinical outcome of the patients (P = 0.0007). In the early stages of cancer (stages I and II), 14-3-3sigma immunoreactivity was absent in 5 of 10 (50.0%) patients who showed recurrence during follow-up, whereas its absence was detected in only 13 of 68 (19.1%) disease-free patients in the same period. In addition, 14-3-3sigma immunoreactivity was absent in 4 of 5 (80.0%) patients who died, whereas its absence was detected in only 14 of 73 (19.2%) patients who had lived during the same period. Patients whose tumors were negative for 14-3-3sigma were at much greater risk to develop recurrent and/or mortal disease (P = 0.0372 and 0.0067). In multivariate analysis using the Cox proportional hazards model, absence of 14-3-3sigma turned out to be statistically independent risk factor in disease-free survival and overall survival even in patients with early-stage disease (P = 0.0321 and 0.0191). CONCLUSIONS: Results of our study showed that loss or absence of 14-3-3sigma determined by immunohistochemistry may be an important tool to identify endometrial carcinoma cases at high risk of recurrence and/or death, who are otherwise not detected by current clinical and pathologic evaluation, especially in the early stages of the disease. In addition, results of 14-3-3sigma immunohistochemistry in the early stage of endometrial carcinoma could contribute to planning postoperative follow-up and adjuvant therapy.

14-3-3 Proteins↗