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AIM: To compare the multidetector-row computed tomography (MDCT) findings of IgG4-related sclerosing cholangitis (IgG4-SC) and extrahepatic cholangiocarcinoma (EH-CCA). MATERIALS AND METHODS: Two radiologists who had no knowledge of the patients' clinical information retrospectively evaluated the CT findings of patients with IgG4-SC (n=33) and EH-CCA (n=39) on a consensus basis. Another radiologist measured the biliary lesions. IgG4-SC was diagnosed using the Japan Biliary Association criteria (2012) or the Mayo Clinic's HISORt criteria. EH-CCA was diagnosed based on surgical findings. RESULTS: Compared with EH-CCA, IgG4-SC exhibited the following findings significantly more frequently: (a) wall thickening alone, (b) concentric wall thickening, (c) smooth inner margins, (d) homogeneous attenuation in the arterial phase, (e) a lesion involving the intrapancreatic bile duct, (f) smooth outer margins, (g) fully visible lumen, (h) a funnel-shaped proximal bile duct, (i) skip lesions, and (j) abnormal pancreatic findings. Conversely, (k) dual-layered attenuation in all phases was significantly more common in EH-CCA. The specificity values of parameters (e-k) were >80%. Regarding dimensions, (l) the biliary lesions were longer in IgG4-SC than in EH-CCA. (m) The diameters of the dilated proximal common bile duct and (n) the dilated proximal intrahepatic bile duct were smaller in IgG4-SC than in EH-CCA. CONCLUSION: A number of CT findings are useful for differentiating between IgG4-SC and EH-CCA. CT findings (e-k) are particularly useful for this purpose.

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We investigated the role of endothelium and vasoconstrictor prostanoids in the norepinephrine (NE)-induced vasoconstriction of isolated rat common carotid arteries (CCAs). Isolated CCAs were cannulated with stainless steel cannulae by the cannula inserting method. NE was administered intra- or extraluminally by a single microinjection. For denudation of endothelium, the intimal surface was gently rubbed with a cotton pellet. NE produced dose-related vasoconstricting responses in isolated arteries with intact endothelium. These responses were attenuated by pretreatment with denudation, OKY046, a thromboxane A2 synthesis inhibitor or indomethacin. The residual responses after denudation were further blocked by OKY046 or indomethacin. All NE-induced responses were blocked by a single injection of prazosin. There were no significant differences in responses between intra- and extraluminal administration of NE. These results show that most vasoconstriction induced by NE via alpha1-adrenoceptors in CCAs is dependent on vasoconstrictor prostanoids distributed both in endothelium and vascular smooth muscle.

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OBJECTIVE: To clarify the behavior of endometrial hyperplasia in a prospective study. METHOD: Fifty-one patients with endometrial hyperplasia were followed up for 6 months. Samples of endometrial tissues were taken by uterine endometrial biopsy every 4 weeks during the first 3 months and at the end of follow-up. RESULTS: In 69% (35/51) of the patients histological picture of the endometrium became normal during the observation period. The lesions persisted in 17% (6/35) of the patients with simple hyperplasia, in 25% (1/4) of those with complex hyperplasia, in 14% (1/7) of those with simple atypical hyperplasia, and in 80% (4/5) of the patients with complex atypical hyperplasia. In the remaining 3 patients with simple hyperplasia, the lesions progressed to complex atypical hyperplasia by the end of follow-up, after showing a normal endometrium. CONCLUSION: Most cases of endometrial hyperplasia, except for complex atypical hyperplasia, disappeared spontaneously within a short period of time.

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We report here a case of peripheral neuroepithelioma arising in the uterine cervix. A 44-year-old female had complained of irregular genital bleeding for several months and was diagnosed as extraosseous Ewing's sarcoma (EOE) from biopsy specimens initially. The tumor cells, which were intensely stained by periodic acid-Schiff (PAS) and digested with diastase, were uniformly small and round, had hyperchromatic nuclei and scant, indistinct cytoplasm. The surgically-removed tumor cells were immunohistochemically stained with antisera against neuro-specific enolase (NSE), tyrosine hydroxylase. In ultrastructural study, neurosecretory granules were observed. Finally we diagnosed this case as peripheral neuroepithelioma (peripheral primitive neuroectodermal tumor, PNET).

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Endothelin (ET) is a potent vasoconstrictor peptide. In this study, we investigated maternal venous plasma ET levels measured by Sandwich-enzyme immunoassay within a week before the onset of labor, and measured plasma renin activity and plasma aldosterone concentration by radioimmunoassay in normal and severely preeclamptic pregnancies. Also, we determined umbilical cord blood pH and gas concentrations after spontaneous vaginal deliveries and cesarean sections. There was a significant (p < 0.01) negative correlation between maternal ET levels within 1 week before the onset of labor and birth weights. There was no significant correlation between maternal ET levels and umbilical gas concentrations. These data suggest that the correlation is the result of decreasing uteroplacental blood flow. We speculate that increased maternal ET expresses not only maternal renal vascular endothelial injury but also other vascular endothelial injuries. These vascular injuries may occur at least 1 week before the clinical manifestation in the preeclamptic mothers and their fetuses.

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Collagen IV is the main collagenous component localized in the trophoblast and glomerular basement membrane. Serum collagen V reflects degradation of basement membrane collagen. In this study, we measured collagen IV levels in maternal serum, umbilical cord serum and amniotic fluid, both from preeclamptic and normal pregnant women, by radioimmunoassay. The serum collagen IV levels in the preeclamptic group were significantly (p < 0.05) higher than those in the normal pregnant group. The amniotic fluid collagen IV level at term was found to be higher than maternal serum collagen IV. We postulate that collagen IV may have an important role in the maintenance of pregnancy. There was a significant positive correlation between maternal serum collagen IV levels and serum laminin levels. There was no significant correlation between maternal serum collagen IV level and blood pressure, urinary protein concentration, or any other laboratory data. These results suggest that there is early damage of endothelial cells in preeclampsia.

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To elucidate the involvement of MAO activity in rat pregnancy, female rats exhibiting at least 3 consecutive 4-day estrous cycles were used. The day of sperm-positive smears was designated as day 0 of pregnancy. The rats were sacrificed on day 2 of diestrus (diestrus-2) and days 7, 14 and 21 of gestation. The organs were collected and weighted, and mitochondrial fractions were prepared for MAO analysis with kynuramine dihydrobromide as substrate. Specific activity (pmol/mg of protein/min) in the ovary is significantly lower in rats on diestrus-2 (792 +/- 127) (mean +/- S.D.) than on day 14 (1,038 +/- 140) and day 21 (1,580 +/- 61) of pregnancy. However, the levels of MAO activity in the uterus of rats on diestrus-2 (899 +/- 266) is higher than on day 21 (570 +/- 80) of pregnancy. The MAO activity in the placenta on day 21 (644 +/- 82) was higher than day 14 (356 +/- 88) of pregnancy. Total MAO activity per organ (nmol/min) of ovary on day 21 (27.2 +/- 5.2) is higher than on diestrus-2 (8.7 +/- 3.0) and on day 14 (14.2 +/- 3.6). Our results suggest that MAO activity in rat reproductive organs such as uterus, ovary, and placenta might fluctuate significantly near term, in correlation with steroid levels, tissue catecholamine contents and so on, in order to maintain pregnancy.

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Brain natriuretic peptide (BNP) was increased in many hypertensive subjects. In this study, we have evaluated maternal, umbilical plasma and amniotic fluid BNP and atrial natriuretic peptide (ANP) in 19 normotensive pregnant women and in 35 preeclamptic patients. The maternal plasma and umbilical cord plasma ANP (p < 0.05) and BNP (p < 0.005) levels were significantly higher than those in normal pregnancy. There was no significant correlation among ANP level, BNP level, clinical symptoms and laboratory examinations. It is suggested that ANP and BNP may be rather a sequel to preeclamptic pathophysiological changes, and may not play an important role as the etiological factor of preeclampsia.

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Laminin is a large noncollagenous glycoprotein localized in the trophoblast and glomerular basement membrane. We measured laminin levels in maternal serum, umbilical cord serum and amniotic fluid, both from preeclamptic and normal pregnant women, by enzyme immunoassay. The serum laminin levels in the preeclamptic group were significantly (p < 0.05 to p < 0.01) higher than those in the normal pregnant group. It has been suggested that laminin plays an important role in implantation of the placenta during early pregnancy. In this study, the amniotic-fluid laminin level at term was found to be lower than maternal serum laminin. We postulate that laminin may not have an important role in the maintenance of late pregnancy. There was a significant positive correlation between maternal serum laminin levels and serum uric acid levels. There was no significant correlation between maternal serum laminin level and blood pressure, urinary protein concentration, or any other laboratory data. These results suggest that there is damage of glomerular and placental spiral arteries in preeclampsia.

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Recently, thromboxane synthetase inhibitor has been used for the treatment of preeclampsia. In this study, we investigated the effects of thromboxane synthetase inhibitor (OKY-046) on placental blood flow (measured with clearance of hydrogen gas generated by electrolysis) in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). The systolic blood pressure of OKY-046-treated SHR (1, 4 and 8 mg/kg) decreased significantly (p < 0.05); however, the systolic blood pressure of WKY did not decrease. The placental blood flow of both OKY-046-treated WKY and SHR did not decrease. We found that OKY-046 has no reducing effect on placental blood flow in rats, and systolic blood pressure of SHR decreases. These data suggest that thromboxane synthetase inhibitor might have a beneficial effect on preeclampsia.

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Endothelin is a recently discovered, potent vasoconstrictive peptide. To investigate its involvement in pre-eclampsia, we measured its concentration in the plasma of 10 healthy non-pregnant women, 19 healthy pregnant women in early pregnancy, 26 healthy pregnant women in the third trimester, 18 women with pre-eclampsia in the third trimester and 6 women with pre-eclampsia in the postpartum period. In addition, the concentration of endothelin in umbilical venous plasma was measured in 7 healthy pregnant women and in 4 with pre-eclampsia. A sandwich-enzyme immunoassay for endothelin-1[1-21] was used. The plasma concentration of endothelin in pre-eclampsia significantly exceeded that of the healthy pregnant women during the third trimester. In pre-eclampsia this elevated level of plasma endothelin normalised with the fall in blood pressure 7 days postpartum. The level of endothelin in the umbilical vein was 6 to 8 times higher than that in the cubital vein both in the healthy pregnant women and in those with pre-eclampsia, but there was no significant difference in the umbilical venous plasma concentration of endothelin between those two groups. These observations suggest that the synthesis of endothelin may be increased in pre-eclampsia and that this increase may play a role in the elevation of peripheral vascular resistance and the production of peripheral ischaemic damage. Damage to the endothelial cells may then stimulate the synthesis of endothelin to initiate a vicious cycle.

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The effect of nifedipine on placental blood flow was investigated in spontaneously hypertensive rats (SHR) and compared with that in normotensive Wistar Kyoto rats (WKY) by means of the clearance of hydrogen gas generated by electrolysis. The placental blood flow of nifedipine-treated WKY (5, 10 and 25 mg/kg) was significantly (p < 0.05) reduced compared with that of WKY control. On the other hand, the placental blood flow of nifedipine-treated SHR did not change compared with that of SHR control. These data suggest that nifedipine has different effects on placental blood flow in SHR and WKY.

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Recently, prostacyclin (PGI2) has been used for the treatment of preeclampsia. In this study, we investigated the effects of PGI2 on placental blood flow (measured with clearance of hydrogen gas generated by electrolysis) in normotensive Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). The placental blood flow of PGI2-treated SHR (0.25, 0.5 and 1 mg/kg) was significantly (p less than 0.05) reduced compared with WKY. These data suggest that PGI2 has a certain reducing effect on placental blood flow in SHR; on the other hand, in WKY, it has an increasing effect depending on the dose.

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To clarify the possible role of elevated atrial natriuretic peptide (ANP) in the pathophysiology of preeclampsia, we measured ANP, renin activity (PRA), angiotensin II (Ang II), TXB2 (a stable metabolite of TXA2) and 6-keto-PGF1 alpha (a stable end product of PGI2) concentrations in the plasma of 19 normal pregnant women and 35 severe preeclamptic patients at term. Plasma ANP levels in the preeclamptic patients (n = 35, 71.5 +/- 3.8 pg/ml, mean +/- S.E.) and also umbilical plasma ANP (n = 35, 83.0 +/- 4.2 pg/ml) were significantly (p less than 0.01) higher than those of normal pregnant women plasma (n = 19, 58.7 +/- 3.7 pg/ml) and umbilical plasma (n = 19, 47.6 +/- 4.7 pg/ml). There was a significant (p less than 0.01) positive correlation between maternal ANP levels and fetal ANP levels (n = 54, r = 0.44). Plasma PRA and 6-keto-PGF1 alpha levels in preeclampsia were significantly (p less than 0.05) lower than those of normal pregnancy. The ratio of 6-keto-PGF1 alpha/TXB2 in preeclampsia was significantly (p less than 0.01) lower than that of normal pregnancy as we reported previously. There was no significant correlation between plasma ANP level and plasma PRA, Ang II, plasma TXB2 and 6-keto-PGF1 alpha concentrations. Moreover there was no significant correlation between plasma ANP level and the severity of preeclampsia. These data suggest the possibility of a transplacental crossing of ANP secreted by feto-placental unit, which might be, at least in part, responsible for the high ANP levels observed in preeclampsia. The ANP in preeclampsia is not related directly to hypertension, but it may play a substantial role in the regulation or normalization of blood volume and vascular reactivity.

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Severe preeclampsia in the second trimester presents a major challenge in management because it is associated with high perinatal mortality. One possible way to improve the perinatal outcome in these pregnancies is to predict the later development of preeclampsia and to start management of it early. To investigate the relationship between the timing of the rise in maternal mean arterial pressure (MAP) and the course of biparietal diameter (BPD) growth in the fetus, we reviewed seven women with preeclampsia diagnosed between 18 and 27 weeks' gestation. MAP increased slowly within the normal range three or four weeks before the onset of the disease. Slowing of the fetal BPD growth curve preceded the onset of preeclampsia by two to four weeks. Serial measurement of BPD from early pregnancy may prevent the onset of severe preeclampsia before 28 weeks' gestation.

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In order to study the effect of gossypol on the monoamine oxidase (MAO) activity in pregnant rat organs, 20 day pregnant rats were sacrificed, and MAO activity/0.02 g tissue of several organs and total MAO activity/organ, were determined. The control group (n = 5) were injected with vehicle intramuscularly on the 17th, 18th and 19th day of pregnancy, and the gossypol treated group (n = 4) were injected with gossypol acetic acid (GAA) (25 mg/kg of body weight) intramuscularly on the 17th, 18th and 19th day and were decapitated on the 20th day of pregnancy. Maternal liver, uterus, placenta, and fetal liver were collected and examined. In placenta, total MAO activity/organ was significantly (p less than 0.05) lower in the GAA treated group than that in the control group. However, in maternal liver, uterus and fetal liver, there was no significant difference in total MAO activity/organ between the two groups. There was no significant difference in MAO activity/0.02 g tissue (specific activity), weight of organ, protein weight/organ and protein/g tissue between the two groups in maternal liver, uterus, placenta and fetal liver. These results suggest that, after intramuscular injection of GAA, total MAO activity/organ in the placenta of pregnant rats might decrease significantly.

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In this study, we present our initial trials in the treatment of 6 cases of severe preeclampsia with thromboxane synthetase inhibitor (OKY-046). Following the treatment with OKY-046, maternal systolic blood pressure decreased significantly and umbilical artery waveforms were normalized. These data suggest that thromboxane synthetase inhibition might have a beneficial effect on preeclampsia.

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Recently, ketanserin (serotonin receptor antagonist) has been reported to be beneficial in the treatment of preeclampsia. In this study, we investigated the effects of ketanserin on the placental blood flow, fetal weight and placental weight in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). We measured the rats' placental blood flow by monitoring the clearance of hydrogen gas generated by electrolysis. In ketanserin (12, 24, 48 mg/kg)-treated SHR, systolic blood pressure was significantly decreased. The placental blood flow was significantly (p less than 0.05) reduced compared to that before treatment in WKY and SHR. The fetal weight decreased dose dependently in WKY, while in SHR it did not decrease significantly. The placental weight of ketanserin-treated rats decreased compared to that before treatment. These data suggest that ketanserin might have some reducing effects on placental blood flow, fetal weight and placental weight proportional to the dose.

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