Yuichiro Takahashi

Uterine contractions increase fetal heart preload

The preload index (PLI) has been shown to increase in the recipient fetus of twin–twin transfusion syndrome in the presence of uterine contractions. The objective of this study was to determine whether there are changes in PLI in the presence of uterine contractions in normal fetuses.

Characterization of growth-restricted fetuses with breakdown of the brain-sparing effect diagnosed by spectral Doppler

Objective : To characterize serial findings of the middle cerebral artery (MCA) and umbilical artery (UA) flow patterns, their relationship to each other, and neonatal outcomes in growth-restricted fetuses. Methods : Serial pulsatility indices (PIs) from MCA and UA Doppler waveforms were measured in 41 growth-restricted fetuses until Cesarean delivery. We found three patterns, as follows: phase 1 ( n = 27), UA PI < MCA PI (no brain-sparing effect); phase 2 ( n = 11), UA PI > MCA PI (brain-sparing effect); phase 3 ( n = 3), both PIs elevated with the absence of end-diastolic flow or presence of reverse end-diastolic flow, which was designated as the breakdown of the brain-sparing effect. Umbilical cord blood gas data at delivery were compared between each group. Results : Age at delivery and body weights were significantly different for each phase. The mean body weights in all phases were significantly diminished from Japanese standard body weights, indicating growth restriction. The phase 3 pH and base excess were significantly different from those of the other two phases. Conclusions : Growth-restricted fetuses which suffered from the state of breakdown of the brain-sparing effect were delivered early with severe growth restriction and mild metabolic acidosis. The change from decreased to increased MCA PI along with increasing UA PI may predict a severely growth-restricted infant.

Effects of sex steroids on silver stained proteins of nucleolar organizer regions (Ag-NOR) in the rabbit uterus.

Silver staining of argyrophilic proteins of nucleolar organizer regions (Ag-NOR) has been used to evaluate a hyperactive state of cells. We studied the effects of sex steroids on the Ag-NOR proteins in the rabbit uterus. Estradiol-17beta (E2) caused uterine hypertrophy and increased the number of Ag-NOR dots in epithelial and stromal cells of the endometrium and smooth muscles cells in a dose dependent manner without proliferative change in the endometrium. Progestins including progesterone, medroxyprogesterone acetate (MPA), and norethindrone following E2 caused progestational proliferation of the endometrium with an increase in the Ag-NOR number to various extents, whereas methyltestosterone, a synthetic androgen, caused only a minimal proliferative change in the endometrium without an increase in the Ag-NOR number. Western blot analysis revealed that progesterone and MPA increased the amounts of a 100 kDa protein (nucleolin) and a 37 kDa protein (B23 protein) in the endometium and a marked proliferative change, whereas E2 did not. These results suggest that although the Ag-NOR number was enhanced by both progestin and estrogen, only progestins substantially increase the Ag-NOR protein in the rabbit uterus. This implies that an increase in the amount of nucleolin and B23 protein is associated with the proliferative potential of the cells.

Leptin as an acute stress-related hormone in the fetoplacental circulation

OBJECTIVE To investigate the relationship between fetoplacental leptin secretion and blood gases. METHODS We measured the levels of umbilical arterial and venous leptin, umbilical cord gas, umbilical venous blood glucose, and estradiol‐17β (E2) in 89 pregnant women. Correlation between the leptin levels and other variables (gestational age, birth weight, maternal body weight, height, body mass index, maternal body weight gain, placental weight, umbilical cord gas data, and levels of umbilical venous blood glucose and E2) were examined statistically. RESULTS Umbilical arterial and venous leptin levels were 7.64 ± 12.76 and 7.76 ± 13.17 (ng/mL), respectively, correlating positively with carbon dioxide pressure levels (r = 0.446, P < .001; r = 0.406, P < .001, respectively) and correlating inversely with pH (r = −0.337, P = .001; r = −0.247, P = .019, respectively). Umbilical venous glucose, E2, and other factors did not correlate with leptin levels. CONCLUSION Leptin secretion into the fetoplacental circulation may be associated with fetal hypercapnia, suggesting two important roles for leptin: one for basal control of fetal fat tissue and one as an acute stress‐related hormone.

Divalent hammerhead ribozyme targeting template region of human telomerase RNA has potent cleavage activity, but less inhibitory activity on telomerase

The template region of human telomerase RNA is a crucial area for regulating telomerase activity and would be a good target for ribozymes. In fact, potent telomerase inhibitory activity of the ribozyme targeting the GUC sequence of the 5() end of this region (36-ribosome) has been well demonstrated. To search for a more potent ribozyme, we designed a divalent ribozyme to cleave both the phosphodiester bonds following the GUC and the 23 nucleotides downstream of GUA. An in vitro cleavage study showed that this divalent ribozyme cleaved telomerase RNA more efficiently than the 36-ribozyme or the 59-ribozyme to target the GUA. When this ribozyme was introduced into the carcinoma cells, its inhibitory effect on telomerase activity was less than that of the 36-ribozyme. The 59-ribozyme showed minimum activity on telomerase. This implies that, although the divalent ribozyme possesses a potent cleavage activity on hTR in vitro, the 36-ribozyme is most potent to suppress telomerase activity.

Introduction of p21Waf1/Cip1 gene into a carcinoma cell line of the uterine cervix with inactivated p53

In carcinomas of the uterine cervix of which p53 is frequently inactivated by papilloma viruses, gene transfer of p21, effector of p53, is an alternative tool to suppress cell growth. We introduced the p21 gene into HeLa cells. The transfectant with p21 showed a significant growth retardation by blockage of G1 to S transfer of the cell cycle. This cell line showed significantly reduced anchorage-independent growth as well as attenuated telomerase activity. These data suggest that gene transfer of p21 is an effective tool to lead carcinoma cells with inactivated p53 into less malignant phenotype.

Postpartum microangiopathic hemolytic anemia: cases of successful and dismal outcome assisted with plasma therapy

Microangiopathic thrombosis, thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS), seem to occur with certain stresses, including pregnancy. This report documents the clinical outcome with or without plasma therapy and dismal outcomes of two cases with postpartum microangiopathic thrombosis. One carried a pregnancy to successful cesarean delivery and suffered from postpartum TTP/HUS followed by plasma therapy-assisted recovery. Another developed postpartum TTP/HUS and was complicated with subarachnoid hemorrhage. Submission to plasma therapy should always be considered in a woman with postpartum microangiopathic thrombosis.

Silver-stained nucleolar organizer regions in adenocarcinoma of the cervix--a light and electron microscopic study.

An increase in the number of Ag-NORs has been described as a possible marker for histopathological cancer diagnosis. The ultrastructural correlation of the reaction, however, has never been elucidated. In tissue samples of the endocervix of the uterus, we compared the ultrastructural configuration of Ag-NORs with the number of Ag-NORs dots. Light microscopic studies showed that the number of Ag-NORs in adenocarcinoma cells significantly increased, but the relation to the bromodeoxyuridine labeling index was not determined. By electron microscopy, Ag-NORs were only observed in the nucleoli and the nuclear bodies of nuclei. Ag-NORs were localized on all components of the nucleolar structure, but the dense fibrillar component was the predominant site in several cases. The nuclear bodies were exclusively found in adenocarcinoma cells and were argyrophilic. A spotted distribution of Ag-NORs was often found in the nucleoli of adenocarcinoma cells that showed an increased Ag-NOR count. The number of Ag-NORs was attributed not only to the number of nucleoli and nuclear bodies in a nucleus but also to the speckled distribution of silver deposits in a nucleolus. These results imply that the Ag-NOR count is a more definitive indicator of a hyperactive state of the cells than the combined number of nucleoli and nuclear bodies in adenocarcinoma of the uterine cervix.