Follow-up study of symptomatic submucous fibroids after hysteroscopic myomectomy.

PURPOSE OF INVESTIGATION: This study aimed to estimate the effectiveness of hysteroscopic myomectomy for symptomatic submucous uterine fibroids and to identify prognostic factors for persistent or recurrent symptoms. MATERIALS AND METHODS: A total of 237 patients who underwent hysteroscopic myomectomy were divided into three groups according to the classification of the European Society for Gynaecological Endoscopy: Type 0 (n=116), Type I (n=97), and Type II (n=24). Medical records and videotape records of all patients were retrospectively reviewed. RESULTS: Improvement of symptoms was achieved in 100% of Types 0 and I, and 66.7% of Type II. The five-year cumulative symptom-free rates after hysteroscopic myomectomy were 96.7% ± 1.9%, 87.8% 6.7%, and 44.5% ± 12.7% in Types 0, I, and II, respectively. The mean symptom-free periods were 46.2 ± 2.6, 47.7 ± 2.7, and 24.7 ± 6.3 months in Types 0, I, and II, respectively. Logistic regression analysis showed that co-existence of other myomas and Type II were independent prognostic factors for recurrence of symptoms. CONCLUSION: Type I fibroids are a good indication for hysteroscopic myomectomy. In Type II, some patients feel that their symptoms improve, but this curative effect could be temporary.

The relation between causes and onset time of polyhydramnios.

The aim of this analysis was to investigate the onset time and significance of maximum volume of polyhydraminios and whether the tter was associated with causes. This was a retrospective cohort study between 2012 and 2014. A total number of 68 singleton pregancies were analyzed. Gestational age at onset of polyhydramnios was 30.0 ± 2.8 (25-36) weeks in maternal factor, 30.0 ± 3.5 (25- 7) weeks in fetal factor, and 32.3 ± 2.0 (27-37) weeks in idiopathic factor. Median of maximum amniotic fluid index (AFI) was gnificantly late onset in idiopathic factor. Diabetes, gestational or pre-existing, was present in all of women (ten cases) in maternal facror. Higher AFI was found to be associated with an increased frequency of prenatally detected congenital anomalies. Abnormal fetal kary- type noted in 18/45 (40%) cases of polyhydramnios. Polyhydramnios diagnosed on ultrasound requires further maternal and fetal iagnostic tests.

Histologic chorioamnionitis prevalence in patients with premature rupture membranes.

This was a retrospective cohort study between 2002 and 2011. A total number of 150 singleton pregnancies with preterm premature rupture of membranes (PROM) (before 34 weeks) were analyzed. Histological chorioamnionitis (Blanc grade III) was significantly increased over three days from onset of premature rupture of membranes. The positive relationship was strengthened (odds ratios, 3.5; 95% confidence intervals, 1.5-5.2) over three days from onset of preterm PROM. PROM is a risk factor important for histological chorioamnionitis. To avoid neonatal infection, early termination is recommended in preterm PROM patients.

Retroperitoneal leiomyosarcoma: a case report.

Retroperitoneal leiomyosarcoma is a relatively rare and aggressive tumor. Because of its rarity, it is difficult to arrive at a definite diagnosis preoperatively and to design an effective strategy. Here the authors report a case of peritoneal leiomyosarcoma in which diagnosis was difficult because the clinical course resembled that of ovarian cancer. A 77-year-old woman diagnosed with ovarian cancer underwent laparotomy. The excised tumor contained a necrotic polypoid mass that histologically displayed the features of leiomyosarcoma. The patient received adjuvant chemotherapy with a combination of gemcitabine and docetaxel but died two months after surgery owing to the aggressive behavior of the tumor. Because the preoperative diagnosis in this case was ovarian cancer, arriving at a treatment strategy assuming peritoneal leiomyosarcoma was difficult. If complete surgical resection of tumor is not performed, as in the present case, the prognosis can be extremely poor.

Seminoma leading to detection of testicular feminization syndrome: a case report.

The authors here report a 54-year-old (gravida 0, para 0), who claimed to have had her menarche at age 13 and menopause at 52 years. Two months prior to presentation, the subject first noticed a hard but elastic fist-sized mass in the left inguinal region that gradually grew, causing pressure-related pain. Although the external genitalia appeared female, the vagina was short and blind-ending, and no uterus or ovaries were identified on transvaginal ultrasound. Chromosome banding results (G-band method) showed 46XY. Laparoscopy revealed no traces of a vestigial uterus or ovaries; thus, based on the appearance of the external genitalia, a diagnosis of testicular feminization syndrome was made. Pathological testing of the palpable mass led to a diagnosis of seminoma with Leydig cell hyperplasia. Thus, in this case, the development of a seminoma in an undescended testis led to the detection of testicular feminization syndrome.

Rupture risk factors of fallopian tubal pregnancy.

The present authors analyzed patients' backgrounds and pre-surgical findings to clarify the risk factors of rupture of fallopian tubal pregnancy. The surgical findings 113 cases were clearly diagnosed as fallopian tubal pregnancy with or without rupture. Twenty-six cases of fallopian tubal pregnancy were ruptured and 87 cases were not ruptured at the time of operation. The risk factors of fallopian tubal rupture were assessed by Chi-square for independence test and multiple regression analysis. Obesity (BMI over 26), prior birth history, social welfare entitlement, ultrasonography findings of fetal heart movement, and pre-surgical serum beta-hCG level more than 3,000 mIU/ml patient were significantly higher risk in fallopian tubal rupture. Fertility treatment patient were at significantly lower risk for fallopian tubal rupture. Higher beta-hCG levels, especially >3,000 mIU/ml is associated with increased risk of fallopian tubal rupture in ectopic pregnancy.

K-ras mutation in the endometrium of tamoxifen-treated breast cancer patients, with a comparison of tamoxifen and toremifene.

The putative presence of a mutation in codon 12 of the K-ras gene was investigated in the endometrium of tamoxifen (TAM) and toremifene (TOR)-treated breast cancer patients. DNA was extracted from fresh cytologic samples of the endometrium in 86 TAM and 21 TOR-treated breast cancer patients. Mutations were detected by enriched PCR and an enzyme-linked mini-sequence assay (ELMA). K-ras mutation was found in 35 TAM-treated endometrial samples, and in only one TOR-treated endometrium (P<0.003). In 24 premenopausal patients, K-ras mutation was found in seven (43.8%) of 16 patients with less than 47 months of TAM treatment, while none was found in eight patients with more than 48 months of TAM treatment (P<0.03). In 62 postmenopausal-amenorrheic patients, K-ras mutation was found in three (15.8%) of 19 patients with less than 23 months of TAM treatment, while it was found in 16 (61.5%) of 26 patients with 24-47 months of TAM treatment and nine (52.9%) of 17 patients with more than 48 months of TAM treatment (P=0.002). The presence of K-ras mutation is significantly influenced by the duration of TAM treatment and menstrual status of the patients. TOR may have a lower potential genotoxicity than TAM.

Time course of Fos and Fras expression in the hypothalamic supraoptic neurons during chronic osmotic stimulation.

The Fos family comprises Fos and several subtypes of Fos-related proteins (Fras) such as FosB, Fra-1, Fra-2, DeltaFosB, and chronic Fras. Changes in the expression of Fos family proteins with time are not well elucidated, particularly during chronic stimulation. In the present experiments, we investigated quantitatively the time course changes in Fos, FosB and Fras immunoreactivity in the magnocellular neurons of the supraoptic nucleus (SON) during acute and chronic osmotic stimulation. A small number of Fos- and FosB-positive neurons were observed in the SON of control rats, while many Fras-positive neurons were seen in control animals. Significant increases in the numbers of Fos-, FosB-, and Fras-positive neurons were observed 2 h after acute osmotic stimulation by intraperitoneal (i.p.) injection of 3% NaCl solution. Although the number of Fos-positive neurons returned to the control level 4 h after i.p. injection, a significant number of FosB- and Fras-positive neurons were still observed 8 h after i.p. injection. During chronic osmotic stimulation by giving 2% NaCl solution for 2 and 5 days, a large number of Fos-positive neurons were observed, but the cessation of chronic osmotic stimulation by normal water drinking immediately decreased the number of Fos-positive neurons to the control level within 2 h. The number of FosB-positive neurons was increased with period of chronic osmotic stimulation, and a significant number were observed 2-8 h after the cessation of the stimulation. The number of Fras-positive neurons was also significantly higher during chronic osmotic stimulation, and this number was significantly high 2-8 h after the cessation of the stimulation. RT-PCR analysis demonstrated the persistent expression of c-fos mRNA in the SON during chronic osmotic stimulation. These results suggest that c-fos mRNA and Fos protein are constitutively elevated during chronic osmotic stimulation and the time course changes in Fos are different from those seen in FosB and Fras.

Intracellular cleavage of glycosylphosphatidylinositol by phospholipase D induces activation of protein kinase Calpha.

Many proteins are anchored to the cell membrane by glycosylphosphatidylinositol (GPI). One of the functions proposed for the GPI anchor is as a possible mediator in signal transduction through its hydrolysis. GPI-specific phospholipase D (GPI-PLD) is a secretory protein that is suggested to be involved in the release of GPI-anchored protein from the membrane. In the present study we examined how GPI-PLD is involved in signal transduction. When introduced exogenously and overexpressed in cells, GPI-PLD cleaved the GPI anchors in the early secretory pathway, possibly in the endoplasmic reticulum, resulting in an increased production of diacylglycerol. Experiments in vitro and in vivo showed that the association of protein kinase Calpha (PKCalpha) with membranes was increased markedly by expression of GPI-PLD in cells. Furthermore, sucrose-density-gradient centrifugation and immunofluorescence microscopy demonstrated that PKCalpha was translocated to the endoplasmic reticulum membrane in cells expressing GPI-PLD, in contrast with its association with the plasma membrane in cells treated with PMA. We also confirmed that the phosphorylation of c-Fos as well as PKCalpha itself was greatly enhanced by the expression of GPI-PLD. Taken together, these results suggest that GPI-PLD is involved in intracellular cleavage of the GPI anchor, which is a new potential source of diacylglycerol production to activate PKCalpha.

Activation of coagulation factor VII by tissue-type plasminogen activator.

To investigate the effect of tissue-type plasminogen activator (t-PA) on blood coagulation, we examined the effects of the addition of t-PA to normal pool plasma (NPP) on clotting times such as diluted prothrombin time (PT) and kaolin clotting time (KCT). The diluted PT but not the KCT was significantly shortened by the addition of t-PA to NPP compared with the normal controls, suggesting a t-PA-induced activation of blood coagulation through factor VII (FVII) activation. The activated factor VII (FVIIa) concentration in the NPP was significantly increased by the addition of t-PA. Although the FVIIa formation was not observed following the incubation of purified FVII with only t-PA or plasminogen, an increase in the FVIIa level was observed after the incubation of purified FVII with t-PA together with plasminogen, or only plasmin. This plasmin-mediated FVIIa formation was also confirmed by Western blotting. These findings suggest that t-PA enhances the activation of the coagulation system through FVII activation.

Serum macrophage colony-stimulating factor (M-CSF) level is elevated in patients with old cerebral infarction related to vascular damage.

We measured the serum levels of macrophage colony-stimulating factor (M-CSF) in 37 patients with an old cerebral infarction who had been surmised to have a damaged vessel wall and who had been in a stable condition for over three months after stroke onset, and those of 41 healthy control subjects. The M-CSF levels in the patients were significantly higher (P < 0.01) than those of the controls at 1320.4 +/- 410.6 unit/ml and 853.9 +/- 180.3 unit/ml, respectively. The plasma levels of von Willebrand factor (vWF) antigen (P < 0.01) and thrombomodulin (TM) (P < 0.05), as well as those of thrombin-antithrombin III (TAT) complex (P < 0.05), prothrombin fragment 1+2 (F1+2) (P < 0.02), D-dimer products of crosslinked fibrin degradation products (D-dimer) (P < 0.01), and plasmin-antiplasmin (PAP) complex (P < 0.05) in the patients were also significantly higher than those in the controls. Significant positive correlations (P < 0.01) were found between these parameters and the M-CSF level, but there was no significant correlation between the M-CSF level and the white blood cell count, serum lipids, or blood pressure. Based on these results, we suggest that an increased M-CSF level indicates vascular damage or a thrombotic state in patients with an old cerebral infarction.

Posttranslational modification of glycosylphosphatidylinositol (GPI)-specific phospholipase D and its activity in cleavage of GPI anchors.

Human glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) was exogenously expressed in mammalian CHO cells and in insect H5 cells. GPI-PLD was initially synthesized as a 105-kDa form and then secreted as a mature 115-kDa form from the CHO cells, whereas it was secreted as an immature 98-kDa form from the H5 cells. The difference of the molecular forms was caused by its oligosaccharide processing in the two cell lines. These forms showed a different reactivity to anti-C-terminal peptide of GPI-PLD; the 105-kDa and 98-kDa forms were directly recognized by the antibodies, whereas the 115-kDa form was immunoreactive only after being denatured. In an in vitro assay, the 98-kDa form but not the 115-kDa form was able to release a significant amount of GPI-anchored proteins from intact membranes, although the two forms had the same GPI-anchor cleavage activity in the presence of detergents. In addition, a GPI-anchored protein, when coexpressed in CHO cells, was intracellularly cleaved by GPI-PLD in the secretory pathway. Taken together, these results suggest that GPI-PLD undergoes a conformational change by posttranslational modification, which affects its immunoreactive and enzymatic properties.

Small-cell carcinoma of the endometrium: an immunohistochemical and ultrastructural analysis.

Small-cell carcinoma of the endometrium is a rare neoplasm, and its aggressive behavior has been reported. We report a case of small-cell carcinoma occurring primarily in the endometrium of a 62-year-old woman with postmenopausal vaginal bleeding and lower abdominal pain. The excised uterus showed a necrotic polypoid mass and histologically displayed an endometrial small-cell carcinoma. Immuno-histochemically, the tumor cells were positive for cytokeratin, the epithelial membrane antigen, neuron-specific enolase, and chromogranin, but were negative for the leukocyte common antigen and Grimelius stain. Ultrastructural analysis revealed the presence of dense core granules in the cytoplasm of tumor cells. The patient died 2 months after surgery because of aggressive behavior of the tumor. We wish to distinguish small-cell carcinoma of the endometrium from conventional epithelial tumors of the endometrium, because of the former's distinctive histopathologic, immunohistochemical, and ultrastructural characteristics.

Studies of the pathogenesis and management of thrombotic thrombocytopenic purpura.

We have studied the pathophysiological signs and methods of management of thrombotic thrombocytopenic purpura (TTP) in our TTP patients. We showed that anti-platelet GP II b- III a monoclonal antibodies bound to human vascular endothelial cells (HUVEC). The binding rate of 125I-anti-platelet GP II b- III a monoclonal antibodies to HUVEC treated with TTP patients sera was decreased, compared with the value observed for HUVEC treated with normal sera. These findings showed that GP II b- III a like substances are expressed on HUVEC and that TTP patients sera appear to contain anti-platelet GP II b- III a antibodies which may attack and injure the endothelial cells. PGI2 stabilizing activity of plasma is measured by PGI2 inhibitory activity attenuation on normal platelet aggregation induced by ADP. PGI2 stabilizing activity decreases in acute phase, increases in remission, suggesting that there may be a relationship between pathogenesis of TTP and decreases of PGI2 stabilizing activity. We also showed that PGI2 analogue (beraprost sodium) was useful for prevention of relapse of TTP. Plasmapheresis has emerged as the treatment of choice of TTP. We found the effectiveness of the high molecular weight fraction (HMW-F) of plasma in chronic TTP patients. HMW-F of plasma may contain the main factor necessary for improvement of TTP.

Enhancing effect of platelets on staphylokinase-mediated clot lysis and plasminogen activation.

The effects of platelets on clot lysis and plasminogen activation by staphylokinase (SAK) were investigated. At concentrations ranging from 2 x 10(-7) to 1 x 10(-5)g/ml of SAK, the lysis time of platelet-rich plasma clots (PRP-clots) was shorter than that of platelet-poor plasma clots (PPP-clots). This reduction of clot lysis time was observed in a dose-dependent manner on platelet count in PRP. The activation rate of plasminogen by SAK measured by the amidolytic method using S-2251 was enhanced by the addition of washed platelets. These enhancing effects of platelets on clot lysis and plasminogen activation were not altered by pretreatment of platelets with indomethacin and theophylline, but were diminished by platelet disruption. Thus, we concluded that platelets enhance fibrinolytic activity of SAK, and this effect is not due to the release reaction or intracellular contents of platelets, but to the existence of platelet surface in the intact shape as a catalytic site for fibrinolysis.

Solvent extraction clean-up for pre-treatment in amino acid analysis by gas chromatography. Application to age estimation from the D/L ratio of aspartic acid in human dentine.

Solvent extraction, a clean-up method for samples for the determination of amino acids by gas chromatography, was investigated and compared with a conventional ion-exchange purification. Amino acids were esterified with isopropanol and extracted with various organic solvents. The solubilities of the amino acid isopropyl esters increased with increasing solvent polarity and the size of the amino acids. The optimum pH was found to be 10.5. The method was applied to the estimation of ages by measurement of the D/L ratio of aspartic acid in human dentine. The D/L ratios so determined were slightly lower than from the ion-exchange method with respect to all dentines examined. However, there were little or no significant differences in the ages estimated by both methods, and the correlation coefficient of this method was 0.982. The method is suitable for the enantiomeric analysis of amino acids, and has several advantages in the technique and time.