Differential surface structures of invasive and non-invasive Ehrlich ascites tumor cell lines with special reference to the effect of hydrocortisone treatment.

The purpose of this study is to investigate the relation between the fine structure of the tumor cell surface and the tumor malignancy by scanning electron microscopy. Practically, comparison was made between the invasive Ehrlich ascites clone 1 tumor and the non-invasive Ehrlich ascites clone 3 tumor, and also between the 4th postinoculation day and the 6th postinoculation day as regards the growth of microvilli on the cell surface. On the 4th postinoculation day, an invasive clone 1 tumor cell was indistinguishable from a non-invasive clone tumor cell because of their common paucity of microvilli development. On the 6th postinoculation day, the former was associated with exuberant growth of microvilli, and was clearly distinguished from the latter in which the density of microvilli stayed low as before. The appearance of dense microvilli growth in the invasive clone 1 tumor cells chronologically coincided with the stage of fatal bleeding into the abdominal cavity. Hydrocortisone with a dose of 1 mg/mouse, when given subcutaneously to a tumor-bearing mouse on the 4th postinoculation day, stimulated the development of microvilli in both clone 1 and clone 3 tumors. The enhancing effect of the hormone on this process was detectable 2 hours after hormone injection. It was indicated that the dense growth of microvilli in the clone 1 tumor facilitated its tumor invasion into visceral organs, and that the enhancing effect of hydrocortisone on microvilli development was to be related to the promotion of malignant transformation. The possible implications of glucocorticoid in mammocarcinogenesis are discussed from the point of view of comparative endocrinology.     

Monoclonality of both pale cells and cuboidal cells of sclerosing hemangioma of the lung.

Sclerosing hemangioma of the lung remains poorly understood, and it is still unclear whether this lesion is neoplastic or not. It consists of two major cell types, pale cells and cuboidal cells. We analyzed the clonality of each cell types from six female cases of surgically resected sclerosing hemangioma. The pale cells and cuboidal cells were separated by microdissection from methanol-fixed sections, and DNA was extracted for clonal analysis based on an X-chromosome-linked polymorphic marker, the human androgen receptor (HUMARA) gene or the phosphoglycerate kinase (PGK) gene. The HUMARA and PGK genes were found to be amplified with or without digestion by the methylation-sensitive restrictive endonuclease HpaII. Five of six cases were informative. Pale cells and cuboidal cells showed the same monoclonality in all of the informative cases, whereas the control cells showed a polyclonal pattern. Our results demonstrated that sclerosing hemangioma is caused by monoclonal expansion of cells, confirming that it is a neoplasia. Moreover, the present data indicate that both pale cells and cuboidal cells are derived from the same cell.     

Influence of ileal pouch capacity and anal sphincteric function on the clinical outcome after ileal pouch-anal anastomosis

This study was designed to determine the influence of ileal pouch capacity and anal sphincteric function on the clinical outcome after ileal pouch-anal anastomosis. A total of 24 patients who had undergone ileal pouch-anal anastomosis (J pouch) for ulcerative colitis were studied. The 24-hour stool frequency was found to be inversely correlated with the sensitivity threshold volume (STV), maximal tolerance volume (MTV), and distensibility, but was independent of the maximal resting pressure and maximal squeeze pressure. Patients experiencing nocturnal fecal incontinence had maximal resting pressures that were significantly lower than those of nocturnally continent patients. Among the patients with fecal incontinence, those with frequent soiling had lower resting pressures, STV, and distensibility than the patients with intermittent spotting. In addition, the STV in patients needing nocturnal evacuation were lower than those of patients who did not evacuate after falling asleep. The conclusions are as follows. Both stool frequency and the need for nocturnal pouch evacuation correlated directly with pouch volume. Anal incontinence was more common in patients with low internal sphincteric function. In addition, frequent and gross nocturnal incontinent patients demonstrate a worse function in both the anal sphincter and reservoir than those with intermittent spotting.     

Postoperative local thermo-chemotherapy in control of residual pleural diseases after resection of primary lung carcinoma--regulation of dissemination

Pleural dissemination was proved by intraoperative histodiagnosis in 11 of 121 patients who underwent pulmonary resection for non-small cell carcinoma of the lung between April, 1985 and December, 1986. To control such intrathoracic residual diseases, we devised a means of local thermo-chemotherapy. Ten of 11 patients were treated with intrapleurally administrated cisplatin (50-100mg, bolus) combined with simultaneous radiofrequency hyperthermia (13.56 MHz) for 2 to 3 weeks after surgery. Courses were repeated at 5-to 7-day intervals. Eight patients had N2-disease, one N1 and the other NX. Eight were adenocarcinomas. Thermal burn of the chest wall with hyperkalemia was observed in only one patient who received thermotherapy at the over a magnetrode power of 450 watts for 50 minutes. In the other 9, side effects were minimal under the thermotherapy to obtain a peripleural temperature beyond 42 degrees C. Of the 10 patients, three lived more than 12 months after treatment. Although distant metastases were recognized in 6 cases, none had local recurrence for the median follow-up period of 6 months. One patient had metastasis to the contralateral supraclavicular lymph nodes. Because there was no evidence of intrathoracic recurrences in this patient, radical neck dissection were performed 15 months after the initial operation. This experience warrants further investigation of thermo-chemotherapy as a treatment for controlling pleural dissemination after resection of primary tumor.     

Block of cardiac sodium channels by antiarrhythmic drugs

The effects of seven Class-I antiarrhythmic drugs on the maximum upstroke velocity (Vmax) of action potential were examined in isolated guinea pig ventricular muscles in order to characterize their use- and state-dependent sodium channel blocking action. From the onset and offset kinetics of the use-dependent Vmax inhibition during stimulation trains, the seven drugs were subdivided into two groups; fast drugs (lidocaine, mexiletine, and tocainide), and slow drugs (quinidine, aprindine, disopyramide and flecainide). In experiments to assess the state-dependent sodium channel block, a conditioning clamp pulse to 0 mV was applied by using the single sucrose-gap voltage-clamp technique, and the Vmax of test action potential 100 msec after the clamp pulse was measured. The decrease in Vmax by 10 msec clamp pulse was defined as the activated channel block (ACB), and the decrease in Vmax as the clamp pulse duration was prolonged from 10 to 500 msec was defined as the inactivated channel block (ICB). The ratio of ICB to ACB was less than 1.0 for quinidine, disopyramide and flecainide, and much greater than 1.0 for aprindine, lidocaine, mexiletine, and tocainide. These characteristics may contribute to the differences in efficacy of each drug in treating various types of arrhythmias.     

Effect of OPC-8212 (2(1H)-quinolinone), a new inotropic agent, on myocardial energy metabolism in patients with coronary heart disease

We examined the effects of a new inotrope, OPC-8212 (OPC: 2(1H)-quinolinone), on coronary sinus flow (CSF), myocardial oxygen consumption, myocardial lactate extraction ratio (LER), cardiac index (CI) and pulmonary arterial diastolic pressure (PADP) in eleven patients with prior myocardial infarction. Measurements were taken before (control) and 8 hours after administration of OPC (480 mg, p.o.). A cardiac function curve was obtained in each stage with rapid intravenous administration of 500 ml of saline (loaded state) after baseline measurements. There was a significant increase in the cardiac index and decrease in the pulmonary arterial diastolic pressure in the loaded state after OPC. Thus the ventricular function curve was shifted to the left and showed a steep incline, indicating an increased inotropic state. On the other hand, myocardial oxygen consumption and myocardial lactate extraction ratio were unchanged. Thus we concluded that OPC improved cardiac performance without increasing myocardial oxygen consumption.     

Enzyme-linked Immunosorbent Assay of Pro-gastrin-releasing Peptide for Small Cell Lung Cancer Patients in Comparison with Neuron-specific Enolase Measurement

Our previous study demonstrated that pro-gastrin-releasing peptide(31–98), or ProGRP, is a specific tumor marker in patients with small cell lung carcinoma (SCLC). Using a newly developed, highly sensitive enzyme-linked immunosorbent assay (ELISA) for ProGRP, we analyzed 1,446 samples including those obtained from 478 lung cancer patients to evaluate the clinical usefulness of this ELISA. Several properties indicated that ProGRP is a useful tumor marker for SCLC. First, ProGRP was specifically elevated in SCLC patients. In non-SCLC patients and patients with non-tumorous lung diseases, its serum level was very rarely elevated. Secondly, ProGRP was a reliable marker, in terms of the marked elevation of serum ProGRP levels in SCLC patients. Thirdly, serum ProGRP levels were elevated in SCLC patients even at a relatively early stage of this disease. Fourthly, changes in the serum ProGRP level showed an excellent correlation with the therapeutic responses in SCLC patients. Neuron-specific enolase (NSE) is accepted as a tumor marker of SCLC patients. With the aim of comparing ProGRP and NSE as tumor markers for SCLC patients, we measured serum NSE levels in all samples collected in the present study. We found that ProGRP was superior to NSE in terms of sensitivity, specificity and reliability. Therefore, we consider that ProGRP can play a major role as a clinical tumor marker for SCLC patients.     

A case report of aorto-pulmonary window associated with atrial septal defect]

The patient was a one-year-old boy, who underwent surgery with a diagnosis of atrial septal defect (ASD). During operation, aorto-pulmonary window (A-P window) which had not been detected by the preoperative examinations, was found. Therefore, the A-P window was divided prior to closing ASD. The patient is in good condition six months after the operation. The causes of the inaccurate preoperative diagnosis were discussed.