Yoshiro Kawashima

Serum sialyl Tn as an independent predictor of poor prognosis in patients with epithelial ovarian cancer.

PURPOSE Monoclonal antibody (moAB) TKH-2 directed to the tumor-associated O-linked sialyl 2-6-alpha-N-acetylgalactosaminyl (sialyl Tn; STN) epitope was generated by immunization with ovine submaxillary mucin (Kjeldsen et al, Cancer Res 48:2214-2220, 1988). We investigated whether circulating serum levels of STN antigen might influence the prognosis of patients with ovarian cancer. PATIENTS AND METHODS Serum samples were obtained from 126 healthy nonpregnant women, 157 patients with benign gynecologic disease, and 89 patients with histologically proven epithelial ovarian cancer. Circulating serum STN-antigen concentrations (U/mL) were determined by a competitive radioimmunoassay kit (Otsuka Assay Laboratories, Tokushima, Japan) in a one-step procedure. RESULTS Serum antigen levels were elevated in 48.3% of the patients. The levels of STN antigen were significantly higher in the sera of patients with cancer when compared with levels in benign and healthy controls (P less than .05). The 5-year survival rate for patients with STN-negative (serum STN levels less than 50.0 U/mL) versus STN-positive (greater than or equal to 50 U/mL) tumors was 76.9% versus 10.8%, respectively (P less than .05). The progression-free interval (PFI) at 5 years was 51.9% versus 5.4%, respectively (P less than .05). The overall survival probability and PFI were worse in patients with STN-positive sera. Multivariate regression analysis revealed that stage, residual tumor size, positive STN, performance status, and histologic grade were the five important variables for predicting overall survival. CONCLUSION We conclude that a positive STN-antigen level in sera is an independent predictor of poor prognosis in ovarian cancer.

Collagen types in normal and prematurely ruptured amniotic membranes

Collagen content in preterm amnions with premature rupture of the membranes was significantly lower than that of preterm amnions without premature rupture of the membranes. Collagen types were studied through sodium dodecyl sulfate-polyacrylamide gel electrophoresis in human amnions from pregnant women with or without premature rupture of the membranes. Collagen types I, III, and V were recognized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in all samples. In samples taken from preterm patients with premature rupture of the membranes, the ratios of III/I, III/V, and III/total collagen were significantly lower than those from ones without premature rupture of the membranes. The ratios of I/V, I/total collagen, and V/total collagen showed no change in gestations with and without premature rupture of the membranes, respectively. In term samples there was no significant difference in the ratios of all collagen types between those with and those without premature rupture of the membranes. Elastins were not demonstrable in amnion with and without premature rupture of the membranes. These studies suggest that the reduction of type III collagen content in amnion is related to the cause of premature rupture of the membranes, particularly in preterm samples.

Neurological control of fetal heart rate in 20 cases of anencephalic fetuses

Fetal heart rate (FHR) is influenced by the central nervous system, cardiac automatism, biochemical factors, etc. Changes in FHR were correlated with the anatomic defect in autopsy material from 20 anencephalic infants, and, on this basis, the following hypotheses were formed, subject to later experimental proof. (1) The FHR baseline level is controlled by the medulla oblongata and vagus nerve. (2) The biphasic sleep-awake pattern is controlled by the cerebral cortex. (3) The midbrain is involved in the occurrence of acceleration. (4) A relative high level of short-term variability is shown when small lesions of the lesser central nervous system are present, but we cannot conclude that the cortex is critical for short-term variability. On the other hand, long-term variability seems to be correlated to the presence of the medulla oblongata and midbrain, and might be amplified by the cerebral cortex. (5) U-shaped decelerations are connected with the medulla oblongata, but V-shaped decelerations depend on intracardiac reflexes and myocardial stretch.

Simultaneous determinations of plasma oxytocin and serum placental leucine aminopeptidase (P-LAP) during late pregnancy

1. Plasma oxytocin concentrations were measured by radioimmunoassay in 231 normal pregnant patients. The mean level of the maternal plasma oxytocin increases gradually with advancing pregnancy, culminating in a marked increase during the last two months. 2. Serum placental leucine aminopeptidase (P-LAP) activities and oxytocinase were measured serially in 78 obstetrically normal pregnant patients during late pregnancy. The daily mean P-LAP activity rises progressively during late pregnancy, reaching a relatively high level at 11 days prior to the onset of labor, then fluctuates slightly until the onset of labor. 3. Simultaneous serial measurements of plasma oxytocin levels and serum P-LAP activities in 9 normal pregnant women during late pregnancy show that the onset of labor is preceded by either an increase in the oxytocin level or a decrease in the P-LAP activity.

Clinical evaluation of circulating serum sialyl Tn antigen levels in patients with epithelial ovarian cancer.

Sialyl Tn antigen (NeuAc alpha 2----6GalNac alpha 1----0-Ser/Thr [STN]) with antigenic specificity in the core structure of mucin-type carbohydrate chains has been determined. In the present study, we evaluated the clinical significance of this new carbohydrate antigen, STN, in patients with epithelial ovarian cancer. With the use of a radioimmunoassay developed to detect STN antigen in serum, elevated (greater than or equal to 32.6 U/mL) antigen levels were observed in 50.0% of patients with ovarian cancer. In contrast, 3.8% of healthy individuals had STN antigen levels greater than or equal to 32.6 U/mL. In 9.6% of patients with benign gynecologic diseases and 0% of pregnant women, there were elevated levels of STN antigen. There was a significant difference (P less than .001) in STN antigen levels between patients with ovarian cancer and patients with benign gynecologic diseases, pregnant women, or the controls. The mean +/- SD for all evaluated samples of ovarian cancer was 109.2 +/- 146.8 U/mL. Both the mean values and the positive rate increased as the stage advanced. Classified according to the histologic type, the highest positive rate (61.0%) was observed in mucinous adenocarcinoma. The usefulness of STN antigen as a circulating tumor marker in ovarian cancer was estimated as follows: sensitivity 50.0%, specificity 93.5%, positive predictive value 72.2%, negative predictive value 84.7%, and diagnostic value 46.8%. Serum STN antigen levels were elevated in 12 of 33 patients with ovarian cancer who had serum CA 125 antigen levels less than 35 U/mL. While CA 125 antigen levels were elevated in 74.6% and STN antigen levels were elevated in 50.0% of the same population, the use of both assays indicated the sensitivity of detection of 83.8% in the population studied.

Clinicopathologic study of eight cases of uterine body cancers associated with endometriosis interna (uterine adenomyosis)

Among 30 cases of uterine body cancers, in eight cases (Stage IA, two cases; Stage IB, six cases) uterine adenomyosis was demonstrated microscopically. The age range was from 46 to 66 years with a median of 56. When these eight cases were compared with the 12 cases of Stage I endometrial cancer without adenomyosis, there was no difference in either menstrual history or family history, although past histories of hypertension and diabetes mellitus were found in these eight cases. The mean obesity index was 127 in eight cases and 116 in 12 cases. Seven of these eight cases were pure tubular adenocarcinoma. From the standpoint of early myometrial infiltration of the endometrial cancer, these eight cases not only provided a good model to survey early endometrial cancer but also suggested a common stimulus, such as estrogen, in both endometrial cancer and uterine adenomyosis.

Molecular characteristics of the CA 125 antigen produced by human endometrial epithelial cells: Comparison between eutopic and heterotopic epithelial cells

OBJECTIVE To characterize the CA 125 antigen purified from the conditioned media using an in vitro system that we have established for the culture of epithelial cells from human uterine endometrium. STUDY DESIGN CA 125 was purified separately from the conditioned media of eutopic and heterotopic epithelial cells by gel chromatography and OC 125 immunoaffinity column chromatography. RESULTS Western blot analysis of conditioned media from eutopic epithelial cells revealed a single polydisperse band of 200 kd, whereas two major CA 125 isoforms of 200 and 110 kd, as well as two minor forms of 100 and 70 kd, were observed in heterotopic epithelial cells. The 110 kd CA 125 was more prominent than the 200 kd antigen in heterotopic epithelial cells. CONCLUSION These results strongly suggest that CA 125 antigens purified by immunoaffinity chromatography have different molecular mass in eutopic and heterotopic epithelial cells even though the OC 125 binding site may remain intact.

A comparison of angiotensinase and placental leucine aminopeptidase during normal pregnancy.

1. Serum leucine aminopeptidase activity measured by its action on hydrolysis of L-leucyl-beta-naphthylamide was increased progressively as pregnancy advanced. Angiotensinase activity determined by bioasaay showed parallel increase during normal pregnancy. 2. The effects of heat treatment and L-methionine on the activity of angiotensinase were compared with those on leucine aminopeptidase activity in pregnancy serum.

Real-time analysis of foetal heart rate patterns using a computer system.

The foetal heart rate and uterine contraction curves provide both continuous and real-time information on the foetus. In recent years, attempts have been made to automatically diagnose foetal distress using a computer to provide direct analysis of this information. In the present study, we performed pattern-analysis of the foetal heart rate and uterine contraction curves using a minicomputer on 476 mothers who gave birth at the hospital attached to Hamamatsu University School of Medicine from April 1978 to March 1980. We developed the algorithm for these curves. The algorithm was roughly divided into two groups, original signal process and pattern-recognition algorithms. Following the autocorrelation and noise reduction of original signals, the algorithm was analysed. The algorithmic analysis consisted of the calculation of baseline f.h.r. recognition of deceleration, recognition of uterine contraction, and classification of the deceleration pattern. By using these algorithms, the true diagnostic distribution rate was obtained: early deceleration: 76%, variable deceleration: 88%, late deceleration: 72%, and prolonged deceleration: 81%.

Serum α-cysteine proteinase inhibitor levels in pregnancy

Variation in α-cysteine proteinase inhibitor levels in human sera were investigated with special attention to the effect of pregnancy and diseases. The inhibitor level in 111 pregnant women, examined by our previous method, increased as the pregnancy advanced. The correlation coefficient between the level and the duration, r , was 0.578 with the level of significance p p