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The aim of the present study was to investigate the relationship between assisted reproductive technology procedures, the morphology of the basal plate of placentas, and amount of bleeding in deliveries. Fifty-five whole placentas (fresh-embryo transfer in the in vitro fertilization cycle [n = 6], frozen-thawed embryo transfer in the natural cycle [n = 13] or in the hormonal cycle [n = 10], and age-matched spontaneously conceived pregnancies [n = 26]) were retrospectively enrolled and histologically analyzed. The whole placentas were stored in our pathological division among 512 singleton pregnancies with vaginal deliveries (34-41 weeks of gestation) at Hamamatsu University Hospital. The morphology of the placental basal plate was examined using Azan staining. A total of 20 digital images (each 0.53 mm(2)) of microscopic fields were analyzed per placenta to measure the mean values of the vertical maximum thickness of Rohr and Nitabuch fibrinoid layers and % loss of decidua. The thickness of Rohr fibrinoid layer and % loss of decidua were significantly higher in the frozen-thawed embryo transfer in the hormonal cycle group than in the frozen-thawed embryo transfer in the natural cycle and spontaneously conceived pregnancy groups (each P < .01). The z scores for both the thickness of Rohr fibrinoid layer and % loss of decidua positively correlated with those for the amount of bleeding in deliveries (P < .05 each). Assisted reproductive technology procedures changed the morphology of the placental basal plate, suggesting a possible association with an increase in the amount of bleeding in deliveries.

Recently, we reported that (i) casein kinase I (CK-I) specifically phosphorylates threonine residues on high mobility group protein 1 (HMG1) when incubated with cholesterol-3-sulfate (CH-3S); and (ii) CH-3S directly induces a drastic conformational change in HMG1.1) The latter finding provides a mechanism to explain how CH-3S alone can induce the phosphorylation of HMG1 by CK-I in vitro.HMG1 and HMG2 (HMG1/2) are abundant components of chromatin and a subfamily of the HMG proteins containing the HMG1 box domains is widely distributed in eukaryotic cells from yeast to human.2) It has been reported that (i) both HMG1/2 play important roles in the modulation of transcription, DNA integration and recombinations 2) ; (ii) cdc-2-kinase phosphorylates HMG1, and this phosphorylation reduces its DNA-binding affinity in vitro 3) ; (iii) Chironomus HMG1 4) and mouse testis-specific HMG1 5) are phosphorylated by protein kinase C (PKC) and appear to be required for the functioning of DNA-binding proteins, including topoisomerase I-dependent supercoiling activities 5) ; and (iv) HMG1 in Drosophila embryos and in the cultured cells of Chironomus is phosphorylated by CK-II at multiple serine residues located within the acidic tails, and this phosphorylation is important for the proper functioning and turnover rates of HMG1. 6) However, the physiological significance of the phosphorylation of HMG1/2 by these protein kinases (CK-I, CK-II and PKC) in the regulation of inflammatory mediators is not clear in present.Glycyrrhizin (GL) is present in large quantities in the roots and rhizomes of licorice, Glycyrrhiza glabra L., and is composed of a molecule of glycyrrhetinic acid (GA) and two molecules of glucuronic acid. We have been studying the physiological characteristics of the GL-binding proteins (gbPs) involved in inflammatory responses and the inhibitory effect of GL on gbP activities in vitro.7-12) Previously, we reported that (i) CK-II from mouse liver is selectively purified by GL-affinity column chromatography (HPLC) as a gbP 7) ; (ii) GL selectively inhibits the CK-II-mediated phosphorylation of cellular functional gbPs, such as glucocorticoid receptor, 7) lipoxygenase 3, 8) phospholipase A 2 (PLA 2 ) 9) and HIV-1 reverse transcriptase, 10,11) in vitro; and (iii) a GA derivative (oGA) is a potent inhibitor at one tenth the concentration of GL to inhibit the CK-II-mediated phosphorylation of these gbPs, 11) and also inhibiting the PKC-mediated phosphorylation of lactoferrin-binding proteins (angiogenin-1 and lactogenin-like protein) in vitro. 12)To investigate the physiological correlation between GL, HMG1/2 and three protein kinases (CK-I, CK-II and PKC) in vitro, we set out to (i) characterize HMG1/2 from a 0.35 M NaCl extract of calf thymus as gbPs with substrate activities for these protein kinases; (ii) characterize GL, GA and oGA as potent inhibitors of the phosphorylation of HMG1/2 by these protein kinases in vitro; and (iii) determine the inhibitory effect of GL on the DNA-binding ability of HMG1 in vitro. Enzymes ...

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We have treated two patients with extramammary Paget's disease/carcinoma (EMPD/C), a 62-year-old woman and a 78-year-old man. In both patients, lymph nodes in the areas of the bilateral inguinal, external iliac arteries, and abdominal aorta were affected. After surgery, they underwent 5 courses of systemic combination chemotherapy at 4-week intervals to residual or recurrent lymph node metastasis. Each course consisted of 3.5 mg mitomycin C and 50 mg epirubicin (day 1), 0.6 mg vincristine (days 1 and 7), 30 mg cisplatin (days 1, 2, and 3), and 350 mg 5-fluorouracil (days 3, 4, 5, 6, and 7). The affected lymph nodes in both patients subsided in response to the chemotherapy. Positron emission tomography (PET) scans confirmed the complete remission of lymph node metastasis in Case 1. In Case 2, they were reduced by more than 90% on computed tomography (CT) scans. Adverse effects included leukocytopenia, vomiting, hypesthesia, and constipation, all of which disappeared after the completion of chemotherapy. While surgery with wide local excision is the treatment of choice in patients with EMPD/C, there is currently no standardized treatment for advanced cases with metastasis. We describe two patients with EMPD/C whose metastatic lesions responded well to this combination of chemotherapy.