T. Fukaya

Fetal arrhythmia during treatment of pregnancy-associated acute promyelocytic leukemia with all-trans retinoic acid and favorable outcome

Differentiation and subsequent development are intricately interwoven processes operating as an integrated whole to form the organism. As an approach to examine these interactions in early mammalian development, we used embryonic stem (ES) cell in vitro differentiation. ES cells can, depending upon the environment differentiated to neuroectoderm, mesoderm and hematopoietic cells. We developed a serum-free, chemically defined medium (CDM) in which ES cells survive and differentiate. In CDM, in the absence of exogenous factors, ES cells form neuroectoderm, upregulating the early neural marker Pax-6. This is consistent with the view that neuroectoderm development can represent a default state, where the absence or sequestration of mesoderm inducing factors permits neuroectoderm formation. In contrast, if CDM is supplemented with bone morphogenetic protein (BMP) 2 or 4 a process resembling primitive streak formation, least at the molecular level occurs, with the formation of mesoderm and subsequently endothelial and hematopoietic cells. If used with care, ES cell in vitro differentiation can act as a guide in understanding the environment which controls early differentiation events in mammals.

Transcription factor adrenal 4 binding protein as a marker of adrenocortical malignancy.

Adrenal 4 binding protein (Ad4BP) is a transcription factor that regulates the expression of the steroidogenic enzymes and is expressed primarily in steroidogenic cells. We immunolocalized Ad4BP in adrenocortical carcinoma (eight cases) and various malignancies that histologically simulate an adrenocortical carcinoma to evaluate the value of Ad4BP as an immunohistochemical marker of adrenocortical carcinoma. These malignancies examined were renal cell carcinoma (20 cases), hepatocellular carcinoma (10 cases), malignant melanoma (eight cases), ovarian (six cases) and uterine (three cases) clear cell carcinoma, large cell carcinoma of the lung (five cases), and pheochromocytoma (three cases). Nuclear Ad4BP immunoreactivity was observed only in adrenocortical carcinoma cases but not in other tumors examined. Almost all of the adrenocortical carcinoma cells were immunohistochemically positive for Ad4BP including cells associated with bizarre nuclei. These results show that application of Ad4BP immunostain can contribute greatly to the differential diagnosis of adrenocortical carcinoma.

Plasma β-Endorphin Levels in Pregnancy Induced Hypertension Patients

We measured the plasma β-endorphin (β-EP) levels in 11 normal pregnant women at term, 5 severe pregnancy induced hypertension (PIH) patients at term, 11 normal and 5 severe PIH mothers at labor, 11 fetuses who were delivered from normal mothers and 5 fetuses who were delivered from severe PIH mothers. There was a significant(p<0.05) difference in the maternal plasma β-EP at labor between the group without PIH (n=11, 186.9 ± 21.9 pg/ml, mean ± S.E.) and PIH patients (n=5, 108.5 ± 16.4 pg/ml). These data suggests that β-endorphin have a depressor role of a eodogenous cardiovascular regulatory factor in PIH patients during labor.