Mitsuaki Ito

Placenta previa increta/percreta in Japan: A retrospective study of ultrasound findings, management and clinical course

Aim:  Placenta accreta is an abnormally firm attachment of placental villi to the uterine wall, which may cause postpartum hemorrhage resulting in maternal morbidity and mortality. The purpose of the present study was to clarify the incidence, clinical background and prognosis of placenta previa increta/percreta treated with different modalities in Japan.

Placental leucine aminopeptidase/oxytocinase in maternal serum and placenta during normal pregnancy

Placental leucine aminopeptidase (P-LAP), which is identical with cystine aminopeptidase as oxytocinase, was found to be homologous with rat insulin-regulated membrane aminopeptidase (IRAP) by sequence comparison. In the current study, we determined the P-LAP levels in maternal serum and placenta during healthy pregnancy. P-LAP activities in maternal serum increased with gestation and rose to the peak of 80 IU/ml at 38 weeks of gestation. Northern blot analysis revealed the increase of P-LAP mRNA levels in placenta in the third trimester compared to the first trimester. P-LAP protein and related activities could be detected in the conditioned medium of placental tissue, while they could not be detected in that of human umbilical vein endothelial cells. Immunohistochemically P-LAP was positively stained in the apical membrane of syncytiotrophoblast cells throughout the gestation. These results established the normal range of serum and tissue P-LAP levels during pregnancy and the possible source of serum P-LAP, which will be helpful to elucidate the physiological and clinical roles of P-LAP/oxytocinase/IRAP.

Expression of Placental Leucine Aminopeptidase and Adipocyte-Derived Leucine Aminopeptidase in Human Normal and Malignant Invasive Trophoblastic Cells

We recently identified two novel aminopeptidases, placental leucine aminopeptidase (P-LAP) and adipocyte-derived leucine aminopeptidase (A-LAP). Enzymatically, P-LAP degrades oxytocin, vasopressin, and angiotensin III, while A-LAP degrades angiotensin II and kallidin. In this study we investigated the expression and localization of P-LAP and A-LAP in human trophoblastic cells in the normal placenta (n = 26), gestational choriocarcinoma (n = 8), and placental site trophoblastic tumor (n = 3). On immunoblot analysis both P-LAP and A-LAP proteins were detected in normal placenta and five choriocarcinoma tissues, as well as in two choriocarcinoma cell lines. Immunohistochemical staining of normal placental tissues demonstrated that P-LAP was not only localized in villous syncytiotrophoblasts but also highly expressed in extravillous trophoblasts (EVTs) invading the decidua or maternal spiral arteries. The expression level of P-LAP on these invasive EVTs reached a maximum during the late first to second trimesters of pregnancy, and it decreased in the third trimester. Similarly, A-LAP was strongly expressed in EVTs invading the decidua or spiral arteries in the second trimester of pregnancy, while it was weakly or moderately expressed in villous cytotrophoblasts or EVTs located in the cell columns. These two aminopeptidases were more strongly expressed in all eight choriocarcinomas and three placental site trophoblastic tumors and mainly localized to the intermediate-type trophoblastic tumor cells invading the uterine myometrium or stromal vessels. In summary P-LAP and A-LAP were predominantly expressed in the invasive phenotype of EVTs during placentation, as well as in the invasive tumor cells of trophoblastic neoplasms. These results suggest the involvement of these aminopeptidases in invasiveness of both normal and malignant intermediate-type trophoblasts possibly through degradation of specific peptide substrates.

Immunological detection of 4-hydroxynonenal protein adducts in developing pontine and Purkinje neurons and in karyorrhexis in pontosubicular neuronal necrosis.

Four-hydroxynonenal (HNE) has been proposed as an important marker of radical-induced lipid peroxidation. The principal objective of this study was to assess the occurrence of lipid peroxidation in normal perinatal brain and brains with one form of pontosubicular neuronal necrosis (PSN). Immunochemical studies using an antibody against HNE-modified protein were performed in controls aged from 20 weeks of gestation to 64 years, and patients with PSN. Immunohistochemical study showed developmental and aging changes of positive staining in Purkinje cells and pontine neurons (27 weeks-7 months, 50 and 64 years). In addition, karyorrhectic cells in pontine nuclei with PSN were positively stained. Immunoblotting revealed that a 75-kDa protein, which is speculated to be mitochondrial complex-1 protein, was the most intensely expressed among multiple immunoreactive proteins. Our results identified the presence of oxidative stress in the perinatal neuron, and this oxidative stress may contribute to some forms of karyorrhectic death.