Ciliary beat frequency controlled by oestradiol and progesterone during ovarian cycle in guinea-pig Fallopian tube.

The ciliary beat frequency (CBF) of guinea-pig fimbria during the ovarian cycle was measured by video microscopy using a high-speed camera (500 Hz). In the follicular phase, with increasing concentrations of beta-oestradiol ([betaE(2)]) and a low concentration of progesterone ([PRG]), CBF increased from 13.5 to 16 Hz. In the ovulatory phase, with further increase of [betaE(2)], CBF decreased gradually from 16 to 13.5 Hz. In the early luteal phase, with low [PRG] and [betaE(2)], CBF increased to 17 Hz; however, in the middle luteal phase, with increasing [PRG], CBF decreased (12 Hz), and in the late luteal phase, with decreasing [PRG], CBF increased to 15 Hz. Then, in the resting phase, with low [betaE(2)] and [PRG], CBF decreased immediately to 14 Hz. The CBF of the fimbria was measured in guinea-pigs treated with beta-oestradiol benzoate (betaE(2)B) or medroxyprogesterone (mPRG). A low dose of betaE(2)B increased CBF to 14.5 Hz, whereas a high dose decreased it to 11 Hz. A betaE(2) receptor blocker, ICI-182,780, abolished the betaE(2)B-induced CBF changes and maintained CBF at 12.0 Hz. Medroxyprogesterone decreased CBF to 12.5 Hz, and mifepristone (a PRG receptor blocker) abolished the mPRG-induced CBF decrease and maintained CBF at 15 Hz. The addition of both blockers increased CBF to 18 Hz, suggesting that activation of betaE(2) or PRG receptors decreases the CBF of the fimbria. In conclusion, a moderate [betaE(2)] increase maintains a high CBF (15.5 Hz) in the follicular phase, and then further [betaE(2)] increase decreases CBF to 13.5 Hz in the ovulatory phase. In the early and late luteal phase, low [betaE(2)] and [PRG] increase CBF to 17 and 15 Hz, respectively, and in the middle luteal phase a high [PRG] decreases CBF (to 12 Hz). Thus, the CBF of the fimbria was controlled by signals via betaE(2) and PRG receptors in guinea-pigs.

Transcriptional expression of survivin and its splice variants in endometriosis.

Survivin is a novel inhibitor of apoptosis (IAP), and the two splice variants of survivin (survivin-2B and survivin-EX3) have been identified. Gene expression levels of survivin, survivin-2B and survivin-EX3 in 56 ectopic (16 peritoneal red and 16 peritoneal black lesions and 24 ovarian endometriomata) and 13 eutopic endometrial tissues surgically obtained from 42 women with endometriosis (group A) were compared with those in 16 control eutopic endometrium from 16 women without endometriosis (group B) by quantitative RT-PCR analysis. Survivin mRNA expression levels in ectopic endometriotic tissues were significantly higher than those in eutopic endometrium of groups A and B over the whole cycle. Red peritoneal lesions had higher gene expression levels of survivin than black lesions. In contrast, all tissue samples examined showed relatively lower gene expression levels of survivin-2B and survivin-EX3. No cyclic variation was found in survivin and the two splice variants, both in ectopic and in eutopic endometrium. Although there was no significant difference in the ratio of survivin-2B/survivin between ectopic and eutopic endometrium, the ratio of survivin-EX3/survivin in peritoneal endometriotic lesions was significantly higher than that of eutopic endometrium of groups A and B. These results suggest that survivin and survivin-EX3 may be closely linked to escape from apoptosis and the development of endometriosis.

Effects of switching to wen-jing-tang (unkei-to) from preceding herbal preparations selected by eight-principle pattern identification on endocrinological status and ovulatory induction in women with polycystic ovary syndrome.

The objective of this study was to investigate the effects of switching therapy to wen-jing-tang (unkei-to) from previous selected herbal preparations on endocrine levels and induction of ovulation in women with polycystic ovary syndrome (PCOS). Sixty-four anovulatory women diagnosed with PCOS were enrolled in the study. After Kampo diagnosis, subjects received matched Kampo preparations (43 cases: dang-gui-shao-yao-san, 21 cases: gui-zhi-fu-ling-wan) selected by the matching theory of eight-principle pattern identification and Kampo diagnosis based on concepts of the qi, blood, and fluids as the physiologic activity. Fifty-four women who failed to ovulate after an 8-week treatment were randomly allocated to continuation of treatment with the preceding Kampo prescription (continuation group, n = 27) or treatment with wen-jing-tang (switching group, n = 27). Plasma FSH, LH and estradiol levels were measured and ovulation rates were determined at the beginning and after an 8-week treatment with the preceding Kampo prescription, as well as after the subsequent 8-week treatment with the same preparation or wen-jing-tang. No decrease in mean plasma LH level was observed in the 54 women who failed to ovulate among the 64 treated with a Kampo preparation. After the 8-week treatment with wen-jing-tang, plasma LH levels were decreased by 58.2% (p < 0.0001) and 49.4% (p = 0.0005) in the groups switched from dang-gui-shao-yao-san and gui-zhi-fu-ling-wan, respectively. In the group switched from dang-gui-shao-yao-san, a tendency towards increase in plasma estradiol level was observed (1.51-fold, p = 0.055), which was significant compared with that in the group switched from gui-zhi-fu-ling-wan (p = 0.032). The ovulation rate with switching of treatment to wen-jing-tang was significantly higher (59.3%) than that with continued use of the same preparation (7.4%, p = 0.0036). This study confirmed that wen-jing-tang was effective in improving endocrine condition in the treatment of disturbances of ovulation in patients with PCOS without taking eight-principle pattern identification into consideration. This finding indicates that wen-jing-tang is appropriate for use in treating PCOS in women with various constitutions (as determined by the matching theory of eight-principle pattern identification) in clinical practice and may prove to be a potent therapeutic agent with a wide therapeutic spectrum.

Germline polymorphism of p53 codon 72 in gynecological cancer.

OBJECTIVE: To investigate the biological significance of single nucleotide polymorphism at codon 72 of the p53 gene in the development of gynecological cancer. METHODS: p53 codon 72 polymorphism was examined in a total of 354 blood samples from 95 normal, 83 cervical, 108 endometrial and 68 ovarian cancer cases using polymerase chain reaction and restriction fragment length polymorphism techniques. RESULTS: When p53 codon 72 genotype was classified into two subgroups of Arg/Arg and Arg/Pro + Pro/Pro, the Arg/Arg genotype was associated with an increased risk for the development of endometrial cancer (OR = 1.86, 95% CI = 1.06 to 3.26) compared with the Arg/Pro + Pro/Pro genotype (P = 0.0301). The Arg allele also increased the risk of endometrial cancer (OR = 1.42, 95% CI = 0.93 to 1.52) compared with the Pro allele, but no statistical difference was found (P = 0.1031). There was no significant difference in the genotype or allele prevalence between control subjects and cervical or ovarian cancer patients. CONCLUSION: Homozygous Arg at codon 72 of the p53 gene may be a risk factor for developing endometrial cancer in a Japanese population.

Short-term effects of low-dose atorvastatin on inflammatory status and lipid profiles in perimenopausal hypercholesterolemic, hypertriglyceridemic women.

The short-term and small-dose pleiotropic effects of atorvastatin and influence on sex steroid production were investigated in 35 premenopausal and 71 postmenopausal hypercholesterolemic, hypertriglyceridemic women, as well as the temporal differences in these pleiotropic effects. Atorvastatin (10 mg daily) was given for 6 months and fasting lipid concentrations, high sensitive CRP, and coagulo-fibrinolytic parameters were measured at baseline and after 3 and 6 months of therapy. Atorvastatin reduced the low-density lipoprotein cholesterol, remnant-like particle lipoprotein cholesterol, and malondialdehyde-modified low-density lipoprotein cholesterol after 3 and 6 months in both pre- and postmenopausal women. Atorvastatin decreased significantly high-sensitivity C-reactive protein concentration (-47.6% and -58.0%, P<0.01) and tissue plasminogen activator/plasminogen activator inhibitor-1 ratio (-31.8% and -40.0%, P<0.001) after 6 months in pre- and postmenopausal women. There was no correlation between the pleiotropic effects and the improvement in the lipid profile. Furthermore, atorvastatin has no influence on sex steroid production in both pre- and postmenopausal period. The results indicate some short-term pleiotropic effects of small-dose atorvastatin therapy without influence of endocrinological status, which may be important with respect to the early benefits of statin therapy in the perimenopausal hyperlipidemic women.

Diagnostic and therapeutic laser conization for cervical intraepithelial neoplasia.

OBJECTIVE: The clinical efficacy of conservative treatment using Nd-YAG laser technique for cervical intraepithelial neoplasia (CIN) was evaluated in a large series of CIN patients based on the long-term follow-up results. METHODS: We have treated 2107 women preoperatively diagnosed as having CIN by Nd-YAG contact laser conization with vaporization of the base. Their postoperative histologic findings and clinical outcomes were evaluated. RESULTS: The cone specimen was reported as showing that 1956 (92.8%) of 2107 cases had no CIN or CIN 1-3 and 151 (7.2%) cases had invasive diseases. 1956 cases without invasive diseases were followed up for 16 to 252 months. Incomplete excision occurred in 230 (12.3%) of 1874 patients with CIN lesion in the cone specimen, but failure rate (persistence or recurrence) was only 1.2%. 192 (83.5%) of 230 postoperative CIN patients with positive surgical margins showed no abnormal cytology or colposcopy during follow-up period. Preoperative underdiagnosis of biopsy results compared with cytologic or colposcopic findings elevated the risk for incomplete excision and failure rate. CONCLUSION: The combination of laser excision and vaporization of the base was useful to detect unexpected invasive disease and revealed excellent therapeutic effects for CIN. Preoperative cytologic or colposcopic findings should be taken into account for the conservative treatment of CIN.

Chai-hu-gui-zhi-gan-jiang-tang regulates plasma interleukin-6 and soluble interleukin-6 receptor concentrations and improves depressed mood in climacteric women with insomnia.

This study was performed to compare the effects of Chai-hu-gui-zhi-gan-jiang-tang (Saiko-keishi-kankyo-to), an herbal medicine, in improving depressed mood and on plasma interleukin-6 (IL-6) and soluble interleukin-6 receptor (sIL-6R) concentrations with those of anti-depressants in peri- and post-menopausal women. Ninety patients complaining of menopausal symptoms including insomnia who were diagnosed with mood disorder based on DSM-IV were recruited and separated into two groups (Chai-hu-gui-zhi-gan-jiang-tang group was selected on the basis of SHO for 42 cases, while anti-depressants were used for 48 cases), and plasma IL-6 and sIL-6R concentrations were determined before and after three months of the treatment. There were no significant differences in the decrease in both climacteric and Hamilton depression score after treatment between the two groups. Plasma IL-6 and sIL-6R concentrations were significantly lower in the Chai-hu-gui-zhi-gan-jiang-tang group (-34.8 +/- 15.5% and -22.4 +/- 14.6%, respectively) than in the anti-depressant group (7.5 +/- 4.8% and 2.4 +/- 3.8%, respectively) after 3 months of treatment. Correlations between rate of decrease in climacteric score and plasma IL-6 (R = 0.498, P = 0.0056) and sIL-6R (R = 0.512, P = 0.0045) concentrations were observed. Chai-hu-gui-zhi-gan-jiang-tang reduced plasma IL-6 and sIL-6R concentrations in relation to improvement of depressed mood during treatment. The findings of this study suggest that Chai-hu-gui-zhi-gan-jiang-tang has the potential to decrease morbidity by alleviation of stress reactions in peri- and post-menopausal women.

Tumor angiogenesis and molecular target therapy in ovarian carcinomas.

Growth of solid tumors depends on angiogenesis, the process by which new blood vessels develop from the endothelium of a pre-existing vasculature. Tumors promote angiogenesis by secreting various angiogeneic factors, and newly formed blood vessels induce tumor cell proliferation and invasiveness. Ovarian carcinomas have a poor prognosis, often associated with multifocal intraperitoneal dissemination accompanied by intense neovascularization. The degree of angiogenesis of ovarian carcinomas may directly influence the clinical course of the disease. Although a growing body of evidence indicates that angiogenic intensity may play a prognostic role in gynecological malignancies including ovarian carcinomas, the related biological mechanisms remain to be further elucidated. In this review, we describe current knowledge pertaining to mechanisms and regulation of angiogenesis in ovarian carcinomas with special reference to our recent research results.

Transcriptional expression of the genes implicated in angiogenesis and tumor invasion in cervical carcinomas.

OBJECTIVE: Co-expression patterns of the genes implicated in angiogenesis and tumor invasion in cervical carcinoma cells were investigated together with invasive activity of tumor cells. Transcript levels of those genes were also compared between tumor cells and normal cervical tissues. METHODS: Real-time quantitative RT-PCR analysis was conducted on selected 11 genes (total VEGF-A, VEGF(121), VEGF(165), VEGF(189), VEGF-B, C and D, bFGF, dThdPase, MMP-2 and uPA) using 11 cervical carcinoma cell lines and 14 normal cervical tissues. Protein expression of VEGF-C and MMP-2 and invasive activity of tumor cells were evaluated for each cell line by sandwich ELISA and haptoinvasion assay, respectively. RESULTS: Gene co-expression analysis revealed the significant correlation between angiogenic factors and proteinases in malignant but not in normal cervical samples. Gene or protein expression levels of VEGF-C and MMP-2 were well correlated with the number of invaded tumor cells. VEGF-A splicing variants were increased in malignant compared to normal cervical samples but not associated with the invasive activity of the cells. CONCLUSION: VEGF-C and MMP-2 were closely related to invasive phenotype of tumor cells, whereas VEGF-A isoforms were considered to be involved in cervical carcinogenesis.

Comparing the effects of estrogen and an herbal medicine on peripheral blood flow in post-menopausal women with hot flashes: hormone replacement therapy and gui-zhi-fu-ling-wan, a Kampo medicine.

We investigated the association between blood flow in the extremities and hot flashes, and compared change in blood flow following hormone replacement therapy (HRT) and Gui-zhi-fu-ling-wan (Keishi-bukuryo-gan), a herbal therapy in post-menopausal women with hot flashes. Three hundred and fifty-two post-menopausal women aged 46-58 years (mean: 53.4 +/- 3.6 years) with climacteric complaints participated in the study. One hundred and thirty-one patients with hot flashes were treated with HRT (64 cases) or herbal therapy (67 cases). Blood flow was measured with laser doppler fluxmetry under the jaw, in the middle finger and in the third toe. Post-menopausal women with hot flashes (129 cases) showed significantly higher blood flow under the jaw (13.6 +/- 4.13) than women without hot flashes (166 cases) (5.48 +/- 0.84) (p < 0.0001). Blood flow at this site decreased significantly with either therapy (p < 0.0001). On the other hand, the administration of Gui-zhi-fu-lingwan significantly increased (p = 0.002) the blood flow in the lower extremities, whereas HRT decreased the blood flow. Thus, we have demonstrated that Gui-zhi-fu-ling-wan did not affect the activity of vasodilator neuropeptides on sensory neurons of systemic peripheral vessels uniformly. Therefore, Gui-zhi-fu-ling-wan, rather than HRT, is suggested as an appropriate therapy for treatment of hot flashes in the face and upper body with concomitant coldness in the lower body, which is one of the symptoms of menopause.

Fas gene promoter -670 polymorphism (A/G) is associated with cervical carcinogenesis.

OBJECTIVE: To investigate the biological significance of single nucleotide polymorphism (SNP) at Fas gene promoter in cervical carcinogenesis. METHODS: SNP at -670 of Fas gene promoter (A/G) together with human papillomavirus (HPV) types were examined in a total of 279 cervical smear samples and 8 human cervical squamous carcinoma cell lines using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) techniques. RESULTS: 49 patients with high-grade squamous intraepithelial lesion (HSIL) had higher frequency of high-risk HPV and GA + GG genotype than 167 with low-grade SIL (LSIL) and 63 controls. G allele frequency was also higher in HSIL than in LSIL and controls. There was an increased OR (6.00; CI, 1.32-27.37; P = 0.021) for GA + GG genotype in HSIL cases compared to controls among 96 patients with high-risk HPV. 7 of 8 cervical carcinoma cell lines also showed GA or GG genotype. CONCLUSION: Fas gene promoter -670 polymorphism (A/G) may be closely associated with cervical carcinogenesis in a Japanese population.

Vascular endothelial growth factor-C expression and invasive phenotype in ovarian carcinomas.

PURPOSE: To investigate the biological correlation between vascular endothelial growth factor (VEGF)-C expression and invasive phenotype in ovarian carcinomas. EXPERIMENTAL DESIGN: Gene and protein expression levels of VEGF-C in 10 ovarian carcinoma cell lines were correlated with invasive activity of the cells. The correlation between immunohistochemical expression of VEGF-C and tumor aggressiveness in 73 ovarian carcinomas was also examined with respect to clinicopathologic features and patient outcome. RESULTS: VEGF-C gene and protein expression differed remarkably among the cell lines, and there was a statistical correlation among VEGF-C expression, in vitro invasive activity, and matrix metalloproteinase-2 (MMP-2) gene expression and its activity. Anti-VEGF-C and anti-MMP-2 antibodies inhibited the invasive activity of tumor cells. VEGF-C expression in clinical tissue samples was well correlated with clinical stages, retroperitoneal lymph node metastasis, MMP-2 expression, angiogenesis, lymphangiogenesis, and low apoptotic index (AI). The patients whose tumors had strong VEGF-C expression and low AI underwent a poorer prognosis than did those with weak VEGF-C expression and high AI. CONCLUSION: VEGF-C expression is closely related to invasive phenotype and affects the patient's survival in ovarian carcinomas.

Efficacy of the kampo medicine xiong-gui-tiao-xue-yin (kyuki-chouketsu-in), a traditional herbal medicine, in the treatment of maternity blues syndrome in the postpartum period.

This study was to evaluate the clinical efficacy of Xiong-gui-tiao-xue-yin (Kyuki-chouketsu-in), a Japanese traditional herbal medicine, in stabilizing postpartum psychological state. We enrolled 268 women who had a normal delivery in Osaka Medical College Hospital or its affiliated clinics and randomly assigned them to the following two groups: a group of 134 women who received Xiong-gui-tiao-xue-yin (Kyuki-chouketsu-in) at a dose of 6.0 g/day and another group of 134 women without Xiong-gui-tiao-xue-yin (Kyuki-chouketsu-in) (control group). We observed 2.06-fold and 1.67-fold higher incidences of depressive mood and nervousness, respectively, after delivery in the control group than in the Xiong-gui-tiao-xue-yin (Kyuki-chouketsu-in) group. Within 3 weeks of postpartum, there was a significant difference in the incidences of maternity blues between the Xiong-gui-tiao-xue-yin (Kyuki-chouketsu-in) group (15.7%; 21/134) and the control group (32.1%; 43/134) (p = 0.0195). No adverse effects were observed in this study. The results of this study demonstrate the beneficial clinical effects of Xiong-gui-tiao-xue-yin (Kyuki-chouketsu-in) in stabilizing psychological state in the postpartum period. Xiong-gui-tiao-xue-yin (Kyuki-chouketsu-in) can be expected to improve the mental health of women in the postpartum period and prevent maternity blues.

Autologous blood transfusion in patients with placenta previa.

BACKGROUND: Several studies have shown that autologous blood storage during pregnancy is relatively safe for mother and fetus. However, the need for reappraisal of autologous blood transfusion in obstetric patients has been proposed. METHODS: We retrospectively reviewed the cases of placenta previa and low-lying placenta among pregnancies at our hospital during an 18-year period, 1985-2002. The utility of autologous blood transfusion program, which started in 1994 for those with placental positional disorders, was evaluated. RESULTS: Of the pregnancies reviewed, there were 158 cases (1.9%) of placenta previa or low-lying placenta. The number of patients transfused with homologous blood decreased from 27.6% (21/76) in the period before implementation of the autologous blood transfusion program to 8.5% (7/82) after its implementation in 1994. In the latter time period, 39.0% (32/82) of patients with placenta previa and low-lying placenta were phlebotomized and had blood stored. Of those, 71.9% (23/32) were reinfused where one patient (3.1%) needed homologous blood as well. The volume of collected blood per phlebotomy was 367 +/- 65 ml, the total volume of collected blood per patient was 803 +/- 350 ml, and the total of estimated blood loss per patient was 1326 +/- 873 ml. The volume of reinfused blood per patient was 578 +/- 326 ml. CONCLUSIONS: The program of autologous blood collection and transfusion in patients with placenta previa resulted in a decrease in homologous blood transfusion. In our program, we recommend starting blood collection and storage at 32 weeks' gestation and phlebotomize 400 ml per week to reach a volume of stored blood of 1200-1500 ml.

Glutathione-S-transferase and p53 polymorphisms in cervical carcinogenesis.

OBJECTIVE: To investigate the clinical significance of glutathione-S-transferase GSTM1, GSTT1 and p53 codon 72 polymorphisms in cervical carcinogenesis. METHODS: GSTM1, GSTT1 and p53 codon 72 polymorphisms together with human papillomavirus (HPV) types were examined in a total of 198 cervical smear samples using multiplex polymerase chain reaction (PCR) and PCR restriction fragment length polymorphism (RFLP) techniques. RESULTS: Forty-two patients with high-grade squamous intraepithelial lesion (HSIL) had higher frequency of high-risk HPV and null GSTT1 genotype than 102 with low-grade SIL (LSIL) and 54 controls. Thirty-one patients with HSIL had also statistically higher frequency of null GSTT1 genotype than 28 with LSIL among 69 patients with high-risk HPV. There was no statistical difference in p53 Arg, Arg/Pro and Pro genotypes between SILs and controls with or without high-risk HPV. CONCLUSION: GSTT1 null genotype in cervical cell samples may be associated with more severe precancerous lesions of the cervix in a Japanese population. The p53 codon 72 polymorphism is unlikely to be related to HPV status and the onset of cervical cancer.

Changes in serum tumor necrosis factor (TNF-alpha) with kami-shoyo-san administration in depressed climacteric patients.

An herbal medicine (kampo) is widely used to prevent or treat climacteric symptoms. In order to investigate the potential involvement of tumor necrosis factor (TNF)-alpha in susceptibility to mood disorder in climacteric women and to clarify the relationship between immune function and the efficacy of herbal medicine, we compared serum TNF-alpha levels in two treated groups, with and without concurrent use of herbal medicine. This study included 113 consecutive depressed menopausal patients who visited the gynecological and psychosomatic medicine outpatient clinic of the Osaka Medical College Hospital in Japan. Fifty-eight patients were administered kami-shoyo-san according to the definition of above sho. In contrast, 55 patients who were different in sho of kami-shoyo-san were administered antidepressants. Hamilton Rating Scale for depression (HAM-D) scores were determined at baseline and 12 weeks after starting treatment (endpoint). TNF-alpha concentrations were analyzed before and after 12 weeks of treatment. Kami-shoyo-san significantly increased plasma concentrations of TNF-alpha after 12 weeks of treatment, to 17.22 +/- 6.13 pg/ml from a baseline level of 14.16 +/- 6.27 pg/ml (p = 0.048). The percent change in plasma concentration of TNF-alpha differed significantly between the kami-shoyo-san therapy group and the antidepressant therapy group at 4 weeks (12.0 +/- 7.8% and -1.22 +/- 0.25%, respectively, p < 0.01), 8 weeks (19.7 +/- 3.4% and -2.45 +/- 0.86%, respectively, p < 0.01), and 12 weeks (21.3 +/- 5.4% and -6.81 +/- 2.2%, respectively, p < 0.001). We found in this study that kami-shoyo-san, an herbal medicine, increased plasma TNF-alpha levels in depressed menopausal patients. Cytokines may play various roles in mood and emotional status via the central nervous system and may be regulated by herbal medicines, although the interactions are very complex.

Sex differences of abortuses and neonates in women with allo-immune recurrent abortions.

To investigate the possible association of recurrent spontaneous abortions (RSA) of immune aetiologies with neonatal sex differences, karyotyping of abortuses from allo-immune RSA and epidemiological studies on the sex differences of neonates from sporadic aborters was carried out. Allo-immune disorders, as diagnosed by an increased number of shared HLA class II loci and reduced blocking activity of the woman's serum in mixed lymphocyte reaction, were found almost twice (54.9%) as often as auto-immune disorders (29.9%) among a total of 244 women with RSA. Of 33 abortuses karyotyped from women with RSA, 69.7% showed normal female karyotypes, while only 6.1% had normal male karyotypes, indicating that female fetuses are more prone to abort than males. Epidemiological studies revealed that boys were born at a significantly greater incidence of 58.1% in 221 women with a history of sporadic abortion than 47.6% in 893 women with no history of abortion. Moreover, the proportion of women giving birth to boys only was consistently and significantly higher, regardless of repeated deliveries, in sporadic aborters (36.7%) than in women with no history of abortion (19.6%), showing that more boys were born than girls to women with sporadic abortion. It is concluded that male fetuses are more likely to survive than females in allo-immune RSA due to allo-immune reproductive wastage of chromosomally normal female concept in early human pregnancy, and that allo-immune RSA makes up the highest proportion of unexplained RSA.

Conservative excisional laser conization for early invasive cervical cancer.

OBJECTIVE: To investigate the possibility of conservative excisional laser conization for early invasive cervical cancer. METHODS: Four hundred one women with early invasive squamous cell cancer were treated by laser conization and semiradical or radical hysterectomy with pelvic lymphadenectomy. Their histologic findings and clinical outcomes were evaluated retrospectively. RESULTS: Two hundred Ia1 cases without confluent invasion or vessel permeation receiving only laser therapy had no recurrent disease. There was no lymph node metastasis in 123 Ia1 and 24 Ia2 cases with stromal invasion of under 4 mm in depth regardless of confluent invasion and vessel permeation. However, lymph node metastasis was detected in 1 of 13 Ia2 cases with stromal invasion of over 4 mm in depth and in 5 of 41 Ib1 cases. All of these six cases had vessel permeation in the resected specimens. CONCLUSION: Conservative excisional laser conization may be possible for stage Ia cervical cancer with stromal invasion of under 4 mm in depth. However, the risk of lymph node metastasis should be still considered for those lesions with vessel permeation.

Expression of apoptosis-related proteins in adenomyotic uteri treated with danazol and GnRH agonists.

The biologic properties of adenomyosis and the effects of therapeutic agents on adenomyosis were evaluated with immunohistochemistry, terminal deoxy-nucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) method, transmission electron microscopy, and analysis of genomic abnormality. In the adenomyotic endometrium, estrogen receptor (ER) expression was more intense than in the eutopic endometrium during the secretory phase, and bcl-2 was constantly expressed throughout the menstrual cycle. The expression of ER and bcl-2 was weaker in the adenomyotic endometrium treated with danazol than in that treated with gonadotro-pin-releasing hormone agonist (GnRHa), whereas bcl-2 phosphorylated on serine-87 was more intensely expressed in danazol-treated adenomyotic endometrium than in the GnRHa-treated one. The number of TUNEL-positive cells increased in the adenomyotic endometrium treated with danazol or GnRHa. Ultrastructurally, most of the adenomyotic endometrial cells treated with danazol underwent postapoptotic necrosis and formed a cluster of dead cells. In contrast, cells treated with GnRHa underwent typical apoptosis and were sparsely distributed in the adenomyotic endometrium. Analysis of several cancer-related genes showed no microsatellite instability or loss of heterozygosity in adenomyotic tissues. Therefore, we conclude that the occurrence of adenomyosis is correlated to bcl-2 expression regulated by estrogen and ER rather than genetic mutation.

A pilot study of a Kampo formula, EH0202, with intriguing results for menopausal symptoms.

OBJECTIVES: To investigate the effects of EH0202, a Japanese herbal supplement, on the immune and endocrine systems in women with menopausal symptoms. DESIGN AND SUBJECTS: Thirty-two (32) postmenopausal women (53.0 +/- 5.1 years old) presenting with menopausal complaints were enrolled in a clinical study. Patients were given an herbal supplement, EH0202 (6 g per day for 6 months) and were assessed for reduction of their overall symptoms using Greene's Climacteric Scale and Visual Analog Scale. Plasma interleukin-6 (IL-6), soluble IL-6 receptor, tumor necrosis factor-alpha, granulocyte macrophage-colony stimulating factor (GM-CSF), granulocyte-colony stimulating factor, follicle-stimulating hormone (FSH), and luteinizing hormone concentrations were measured before and 6 months after EH0202 administration. RESULTS: There was a significant decrease in the climacteric scale score (p = 0.0007) and visual analogue scale (p < 0.0001) after 6 months of EH0202 treatment. There was significant increase (p = 0.0097) in plasma GM-CSF levels and a significant decrease (p = 0.018) in plasma FSH levels after 6 months of EH0202 administration. CONCLUSIONS: EH0202 (MACH) decreased the plasma FSH level and stimulated myelopoiesis through the cytokine system, thereby clinically reduced menopausal symptoms in postmenopausal women. Therefore, in postmenopausal women, this product probably acts as an immunomodulator and endocrine modulator.