Characteristics of histopathological and ultrastructural features of placental villi in pregnant Nepalese women.

The placenta is an important functional unit for gas transfer between mother and fetus. The placental membrane, consisting of trophoblast layer interposed between maternal and fetal blood, plays an active role for intensity of respiration, but no morphological evidence has been documented. Until now, it has been reported that fetal growth retardation and increased fetal mortality rate usually could be seen at high altitude. In an attempt to find the cause of high perinatal mortality rate in Nepal, this study was undertaken to examine pathologically about 1000 Himalayan placentas obtained in Nepal and Tibet since 1977, and the results were compared with those of 5500 Japanese placentas at Saitama Medical School since 1990. In this study, characteristics of ultrastructural features of the Nepalese placental villi investigated in recent years are reported. (1) The gross characteristics of placental pathology in the Himalayan group were represented by marked subchorionic fibrin deposits and increased chorionic cysts in contrast to low incidence of intervillous thrombosis compared with those of the Japanese group. (2) As characteristics of histological findings of the placental villi between Himalayan and Japanese groups, the incidence of chorangiosis and chorangioma in the Himalayan group was significantly higher than that in the Japanese group. (3) Accompanying an increase of vasculosyncytial membrane (VSM) in the villi, thickness and separation of basement membrane of the syncytium in addition to increased apoptosis of syncytial cell nuclei were recognized. (4) As characteristic ultrastructural features of chorionic villi of Nepalese placentas, an increase of mitochondria and cystic formation of rough endoplasmic reticulum (rER), in addition to appearance of lamellar bodies similar to alveolar epithelial type II cell in organellae of the syncytium, were observed. These ultrastructural changes of the placental villous capillaries may be ascribed to hypervascularization caused by the chronic hypoxic state. It is, therefore, presumed that trophoblast cells may play an important role for gas transfer mechanism under such a hypoxic state at high altitude.

Dominant expression of androgen receptors and their functional regulation of organic anion transporter 3 in rat brain capillary endothelial cells; comparison of gene expression between the blood-brain and -retinal barriers.

Brain and retinal capillary endothelial cells (BCECs and RCECs, respectively) exhibit a barrier structure and function. Comparison of gene expression in these cells could clarify the selective function of each barrier. The purpose of this study was to identify the genes selectively expressed at the blood-brain barrier (BBB) and to clarify the function of the selective gene, androgen receptor (AR). Gene expression was compared by a differential display using conditionally immortalized rat BCECs and RCECs (TR-BBB and TR-iBRB, respectively). A total of 12 gene fragments were identified as the selective genes dominantly expressed in TR-BBB cells. The most selective fragment in TR-BBB cells had the highest homology with the 3'-UTR of human and mouse AR. Rat AR mRNA was detected in TR-BBB cells and the brain capillary rich fraction, but not in TR-iBRB cells. Expression of organic anion transporter 3 (OAT3) mRNA in TR-BBB cells was induced by treatment with dihydrotestosterone (DHT), an AR ligand, and this induction was suppressed by flutamide. Moreover, uptake of benzylpenicillin by TR-BBB cells was also induced by DHT treatment. In contrast, OAT3 mRNA expression in TR-iBRB cells was not affected by DHT treatment. The brain-to-blood efflux rate of benzylpenicillin was not affected by gender. These results suggest that AR is involved in the functional regulation of OAT3 at the BBB, but not at the inner blood-retinal barrier (iBRB), and this regulation is not affected by gender. The BBB function will be affected by the androgen levels in the brain and/or plasma via AR.

Retinal selectivity of gene expression in rat retinal versus brain capillary endothelial cell lines by differential display analysis.

PURPOSE: The retina is a neural tissue especially differentiated for vision and, thus, the inner blood-retinal barrier (inner BRB) specific molecules may play an essential role in maintaining neural functions in the retina. The purpose of the present study was to identify selectively expressed genes at the inner blood-retinal barrier compared with the blood-brain barrier (BBB). METHODS: A comparison of expressed genes between conditionally immortalized rat retinal (TR-iBRB) cell lines and brain capillary endothelial (TR-BBB) cell lines was performed using mRNA differential display analysis and quantitative real time PCR analysis. The rat M-cadherin gene was cloned by performing 5' RACE, and its protein expression was detected by immunoblot analysis. RESULTS: Eight clones were identified as highly expressed genes in TR-iBRB cells including GATA-binding protein-3 (GATA-3), cytosolic branched chain amino transferase (BCATc), and M-cadherin (cadherin-15). The rat M-cadherin gene was cloned from TR-iBRB cells, for the first time, and has >86% amino acid sequence identity to the previously cloned mammalian M-cadherins. Rat M-cadherin expression in TR-iBRB cells was much greater than that in TR-BBB cells as far as mRNA and protein levels were concerned. CONCLUSIONS: M-cadherin, GATA-3, and BCATc are highly expressed in TR-iBRB cells compared with TR-BBB cells and may indeed be involved in unique functions at the inner BRB.

Re-evaluation of secondary amenorrheic patients one year after initial diagnosis: a prospective study.

OBJECTIVES: The aim of the study was to re-evaluate women with secondary amenorrhea one year after the first visit evaluation. STUDY METHODS: One hundred and seventy-five women with secondary amenorrhea were evaluated on the first visit. Their ages ranged from 18 to 29. Secondary amenorrhea was defined by the absence of menses for more than 3 months after excluding pregnancy. Women who were attempting to conceive were excluded from the study. 1) One hundred and two women were anovulatory (2) 36 had hypogonadotropic hypogonadism, 3) 11 had hypergonadotropic hypogonadism, and 4) 21 had hyperprolactinemia, 5) and five fell into other categories. The one hundred and forty-nine women in categories 1) to 3) were followed up for one year after the first diagnosis was made. A monthly progestational agent or HRT (hormone replacement therapy) was given to women with anovulation or hypogonadism, respectively. RESULTS: Of the 149 women in categories 1) to 3), 100 could be evaluated one year after the first diagnosis. There were 31 women whose diagnosis was changed. Anovulation changed to hypogonadotropic hypogonadism in 11 women, oligomenorrhea in four, and normal ovulatory cycle in two. Hypogonadotropic hypogonadism changed to anovulation in nine women, and to normal ovulatory cycle in one. Hypergonadotropic hypogonadism changed to normal ovulatory cycle in two women. CONCLUSIONS: A significant finding is that approximately one third of the women initially diagnosed with secondary amenorrhea, upon re-evaluation within one year had their diagnosis changed. Therefore evaluation of amenorrhea at an appropriate time is critical for proper management.

Three-dimensional sonographic features of placental abnormalities.

OBJECTIVE: To describe three-dimensional (3D) sonographic features of placental abnormalities in utero. METHODS: A total of 6 cases with placental abnormalities (1 chorioangioma, 1 subchorionic hematoma, 2 placental cysts, and 2 subplacental fibromas) from 22 to 34 weeks of gestation were studied with transabdominal 3D sonography. RESULTS: Placental abnormalities could be easily imaged with both two-dimensional (2D) and 3D sonography; however, visualization of the continuity and curvature of structures was more easily accomplished with 3D sonography. In the case with chorioangioma, the thick and rough surface of the tumor was clearly depicted. With the use of color Doppler ultrasound, only a case of chorioangioma was shown to have abundant blood flow within the tumor. In cases with placental cyst and subchorionic hematoma, the wall of the cyst becomes a transparent-like structure, so internal textures can be clearly identified. In the case with subplacental fibroma, the location in relation to the placenta was clearly recognized. CONCLUSION: These results suggest that 3D sonography has the potential to be a supplement to 2D sonography and color Doppler ultrasound in identifying placental masses and provides a novel means of visualizing placental abnormalities in utero.