Fuminori Kobayashi

Mechanism and clinical significance of elevated CA 125 levels in the sera of pregnant women

To clarify the mechanism of CA 125 elevation in maternal sera, serum levels of CA 125 and CA 19-9 were measured in 122 apparently healthy pregnant women (fifth to fortieth week of gestation) and 50 postpartum women (26 term deliveries and 24 second-trimester induced abortions). Serum levels of CA 125 showed an initial increase by the tenth week and then decreased to less than 35 U/ml, remaining below this level until delivery. However, within 1 hour after term delivery or second-trimester induced abortion, the CA 125 levels showed a second increase and decreased rapidly thereafter. In contrast, serum levels of CA 19-9 did not change significantly during these periods. Combined with our previous finding that the decidua contains abundant CA 125 but little CA 19-9, these results indicate that the elevated CA 125 levels in maternal sera originate from the decidual cells affected by chorionic invasion or the placental separation.

Molecular interaction during pregnancy: Biochemical and topological analysis of adult T-cell leukaemia-derived factor, homologous to thioredoxin, in the pregnant human uterus

Adult T-cell leukaemia-derived factor (ADF), homologous to thioredoxin, displays various biological activities, such as radical scavenging action and the reduction of protein disulphide bonds. We examined the biochemical and immunohistochemical localization of ADF in the pregnant human uterus, using two heteroantibodies to ADF, antibody C and W. Immunohistochemically, decidua and trophoblast cells were intensely stained by antibody C. The concentration of ADF-like substance in the decidua was 95.9 ng/mg protein, determined by enzyme-linked immunosorbent assay. The molecular weight of ADF-like substance in these tissues was determined by gel electrophoresis to be 13 kDa, the same as that of recombinant ADF. These findings indicate that abundant ADF is present in decidua and trophoblast cells ; the localization of such a potent dithiol reducing substance may be beneficial in protecting the fertilized egg and placental trophoblasts from the cytotoxic effects of oxygen radicals.

Sarcoma-like mural nodules combined with a microfocus of anaplastic carcinoma in mucinous ovarian tumor

A case of mucinous ovarian tumor with sarcoma-like mural nodules, one of which coexisted with a microfocus of anaplastic carcinoma, was studied by light, electron microscopic, and histochemical examinations. The case suggested that the formation of sarcoma-like mural nodules may be the result of the proliferation of undifferentiated mesenchymal cells which exist beneath the mucinous epithelium by some stimulation like hemorrhage in the cyst wall. Histologically, the mononucleated cells composing the sarcoma-like mural nodules had epithelioid characteristics, particularly at the areas where the covering mucinous epithelium had already detached. The case also suggested that the findings of epithelioid characteristics in the sarcoma-like mural nodules themselves do not imply these nodules to be anaplastic carcinoma, but merely an epithelioid differentiation from undifferentiated mesenchymal cells, namely one of reactive products. However, the existence of a microfocus of anaplastic carcinoma combined with the sarcoma-like mural nodule necessitates a careful histologic analysis of mural nodules for the treatment of patients and the determination of the prognosis.

Immunohistochemical localization and tissue levels of tumor-associated glycoproteins CA 125 and CA 19-9 in the decidua and fetal membranes at various gestational ages.

To investigate the sources and biologic significance of CA 125 and CA 19-9 in amniotic fluid, immunohistochemical and biochemical localization of these tumor-associated glycoproteins in the decidua and fetal membranes was studied. Immunohistochemically, CA 125 and CA 19-9 were localized in the cytoplasm of decidua cells and amnion epithelial cells but not in the chorion and placental tissue. Biochemically, the 12,000 X g supernatant fractions of decidua and amnion tissues contained relatively large amounts of CA 125 and CA 19-9, 73% to 96% of which was present in the cytosolic fractions of these tissues. The CA 125 levels in the amniotic fluid decreased, whereas those of CA 19-9 increased with gestation, which correlated well with the respective levels in amnion tissues. These findings suggest that amnion cells produce and secrete these glycoproteins into the amniotic cavity. However, it is possible that the decidua also secretes CA 125 into the amniotic cavity through the chorion and amnion such as in the case of prolactin.

Analysis of the levels of CA125, carcinoembryonic antigen, and CA19-9 in the cervical mucus for a detection of cervical adenocarcinoma

To verify whether analysis of the levels of CA125, carcinoembryonic antigen (CEA), and CA19‐9 in the cervical mucus is effective for a detection of cervical adenocarcinomas or not, simultaneous measurement of these three tumor markers in the cervical mucus samples from women without gynecologic disorders, with leiomyoma, with cervical squamous cell carcinomas, and with cervical adenocarcinomas was performed. Extremely high levels of CA125 with low levels of both CEA and CA19‐9 were demonstrated in the cervical mucus samples from women without gynecologic disorders and with leiomyoma. The cervical mucus samples from cervical adenocarcinomas showed low CA125 levels with extremely high CEA and/or CA19‐9 levels. Therefore, analysis of the levels of these three tumor markers in the cervical mucus possibly helps in the diagnosis of cervical adenocarcinomas if CEA and/or CA19‐9 show extremely high levels. When a ratio of (CEA + CA19–9)/CA125 was calculated, all women without gynecologic disorders and with leiomyoma showed a ratio <0.5, whereas ten of 11 cases of cervical adenocarcinomas had a ratio ≥0.5. Only one case of microinvasive adenocarcinoma showed a ratio <0.5. Accordingly, the ratio ≥0.5 strongly suggested an existence of cervical adenocarcinoma, although it included some cases of squamous cell carcinomas (four of 17 cases).

Detection of adult T-cell leukemia-derived factor/human thioredoxin in human serum

Adult T-cell leukemia (ATL)-derived factor (ADF), originally defined as an inducer of interleukin-2 receptor/alpha-chain (IL-2R/p55) of human T-lymphotropic virus type I (HTLV-I) positive T cells, is a human homologue of redox-active coenzyme thioredoxin (Trx) of Escherichia coli. In this study, an enzymatic assay system based on the dithiol-dependent insulin-reducing activity of ADF/Trx was established (insulin-reducing assay) to determine the amount of ADF/Trx in human serum using NADPH and Trx reductase purified from human placenta. Insulin-reducing activity was detected in all of the serum samples from healthy volunteers (n = 30) screened by this assay, with a mean +/- SD of 10.9 +/- 2.4 U/l. This mean value corresponds with the concentration of 223 ng recombinant ADF/Trx (rADF/Trx)/ml. Human serum is known to contain several redox-active proteins with ADF/Trx motifs. To differentiate the contribution of these proteins and ADF/Trx to the insulin-reducing activity, the anti-rADF/Trx monoclonal antibody (mAb)-conjugated affinity column-depleted sera obtained from an identical source was used for analysis. The affinity column-depleted sera demonstrated a loss of over 99% of the original activity, while control column depleted sera lost less than 4%. Furthermore, the amount of affinity-purified ADF/Trx molecules eluted from the same column almost corresponded with the amount estimated by the insulin-reducing activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Maternal serum CA125 levels in early intrauterine and tubal pregnancies.

SummaryUsing an immunoradiometric assay, serum CA125 levels were measured in 13 women with a normal pregnancy, 9 with a spontaneous abortion, 3 with a hydatidiform mole, and 15 with a tubal pregnancy. Serum CA125 levels were high in patients with a normal pregnancy (154±169 U/ml; mean±S.D.), a spontaneous abortion (244±258 U/ml), or a hydatidiform mole (54±16 U/ml). In contrast, CA125 levels in patients with a tubal pregnancy (33±25 U/ml) were low, and almost all of those without uterine bleeding (25±9 U/ml) were within the normal range for non-pregnant women (<35 U/ml). The difference between serum CA125 levels with intrauterine pregnancy and with tubal pregnancy may be ascribed to the difference of the amount of decidual tissues at the site of trophoblastic invasion.

Diffuse Cystic Change of a Term Placenta with a Normal Newborn

We recently encountered a case of term placenta with a diffuse cystic lesion of the villi.

Endothelin-1-like immunoreactivity and endothelin receptors in the human placenta from normotensive and hypertensive pregnancies

The levels of endothelin-1-like immunoreactivity (ET-1-LI) and characteristics of endothelin receptors in the chorionic villous tissue of human placenta were determined. The ET-1-LI level in chorionic villous tissue obtained from normal term placenta was 2,450 +/- 940 pg/g wet weight (mean +/- SD, n = 4). Further analysis using gel permeation chromatography and reverse-phase high performance liquid chromatography showed that the main ET-1-LI constituent of ET-1-LI in this tissue was ET-1. Scatchard analysis of [125I]ET-1 binding to the membrane fraction of chorionic villous tissue obtained from term placenta showed high affinity receptor sites with an apparent dissociation constant (Kd) of 23.6 +/- 11.1 pM and a Bmax value of 388 +/- 238 fmol/mg protein (n = 5). The same binding study with [125I]ET 3 showed a Kd of 13.9 +/- 3.8 pM and a Bmax value of 176 +/- 78 fmol/mg protein (n = 5). These results suggest that both ET-A and ET-B receptors (ET-AR and ET-BR) are expressed in chorionic villous tissue. This finding was further confirmed by Northern blot analysis showing the expression of both ET-AR and ET-BR mRNAs in this tissue. ET-1-LI in the umbilical venous plasma of the newborns from women with pregnancy-induced hypertension (PIH) (38.3 +/- 10.4 pg/mL, n = 5) was significantly (P < 0.05) higher than that in the normal newborns from normotensive pregnant women (26.3 +/- 5.2 pg/mL, n = 12). However, in placental chorionic villous tissue obtained from PIH women, both ET-1-LI level and ET binding profile were not different from those in chorionic villous tissue from normotensive pregnant women. These results suggest that the abundant ET-ET receptor system is present in the placental chorionic villous tissue and that this system is not the major factor of the pathogenesis of placental dysfunction occurring in PIH because these systems are similar in normotensive and hypertensive pregnancies.

MR demonstration of reversible periportal abnormal intensity in eclampsia

We present a patient with toxemia of pregnancy and liver dysfunction. Magnetic resonance imaging revealed diffuse periportal abnormal signal intensity in the liver, which resolved as the liver enzyme levels returned to normal values.