Synthesis and antitumor activity of tropolone derivatives. 7. Bistropolones containing connecting methylene chains.

Bistropolone derivatives (4-12) containing differing lengths of linkage between the two tropolone rings were prepared and examined for their antitumor activity in in vitro (KB cell) and in vivo (leukemia P388 in mice) systems. Parent compound 3, related compounds previously prepared, and the new compounds 4-12 were evaluated for inhibitory activity against ribonucleotide reductase by indirect means to measure their effects on the dNTP pool imbalance. Present structure-activity relationship results would suggest that potently active bistropolones in vivo inhibit intracellular ribonucleotide reductase through chelating with the two irons at the two active sites of the enzyme.     

Cervical lung hernia in a case of severe chronic asthma and bronchitis

A case of a bilateral pulmonary hernia of the lungs into the supraclavicular fossae is described. A man, aged 79, with severe chronic asthma and chronic bronchitis due to air pollution, complained of a cervical mass off and on for several years. The herniation was greater on the right side. It could be identified on physical examination by the presence of a soft painless supraclavicular bulge which was exaggerated by strain or cough. Radiologically this herniation could best be identified on lateral cervical roentgenogram. It is said that cervical lung hernia is a rare condition, but in our experience supraclavicular herniation of the lung is not unusual in cases of severe chronic obstructive lung disease.     

Expression of the cell surface antigen detected by the monoclonal antibody A7 in pancreatic carcinoma cell lines

In a previous study, we used a murine monoclonal antibody, A7, against human colon carcinoma as a drug-carrier to treat colorectal cancer.¹ In the present study, we found that MAb A7 also reacted immunohistochemically with 73% of human pancreatic carcinoma cell lines, with the A7 antigen mainly being detected on the cell surface. However, the A7 antigen was found in only 9% of the spent media of these human pancreatic carcinoma cell lines by ELISA. On the other hand, the positive incidence of CA19-9, POA, ferritin, CEA, DU-PAN-2 and SLX in those spent media was 100%, 64%, 64%, 55%, 55% and 36%, respectively. These results suggest that the A7 antigen may only rarely be shed into the sera of pancreatic cancer patients, in which case MAb A7 could be a suitable drug-carrier in targeting chemotherapy for pancreatic cancer patients.     

Rapid detection of mecA gene by nested PCR for diagnosis of methicillin resistance in Staphylococcus aureus]

In recent years, the most common causative organism of hospital infections has been methicillin resistant Staphylococcus aureus (MRSA). The major mechanism of beta-lactam resistance in MRSA is attributed to the production of a specific penicillin binding protein (PBP2'), which is a product of mecA gene, with extremely low binding affinities to beta-lactams. In the present study, we have established a rapid identification method of MRSA by sensitive detection of mecA gene using nested PCR. Nested PCR method amplifying the target DNA in two steps enhanced the efficiency of the second round amplification. By means of this method, mecA gene was successfully detected in clinical samples, such as blood, pus, sputum and feces within 3-4 hrs. Rapid diagnosis of MRSA-bacteremia is particularly important for prevention of sever systemic infection. There are some strains of S. aureus which possess mecA gene in spite of low minimal inhibitory concentration of DMPPC. In these strains expression of mecA gene is induced by contact of beta-lactams and they obtain methicillin resistance. Using nested PCR method, these latent MRSA are rapidly and certainly detectable. This method should be useful for early and effective detection of MRSA hospital infections.     

Surgical repair of total anomalous pulmonary venous connection in neonates and infants--prevention for pulmonary venous obstruction at the site of anastomosis

From October, 1980, to June, 1987, thirty-eight infants less than one year old underwent correction for total anomalous pulmonary venous connection (TAPVC). Overall operative mortality and late mortality were 13% and 6%, respectively. Residual pulmonary hypertension was noted in 4 patients: three had pulmonary venous obstruction at the site of atrial anastomosis (PVOA) and one had supracardiac (Ia) lesion left after repair of mixed type (IV: Ia + III) of TAPVC. Two late deaths occurred in these with PVOA. Twenty-two patients with supracardiac (I) or infracardiac (III) TAPVC were divided into three groups according to the technical development in atrial anastomosis: the large anastomosis in which venous incision reached into at least one pulmonary vein beyond common pulmonary vein and the continuous running suture were used in 10 patients (group 1), the appropriate size of anastomosis in which venous incision limited within the common pulmonary vein and the continuous running suture used in 4 patients (group 2), and the appropriate size of anastomosis and the interrupted suture in 8 patients (group 3). PVOA were 3 (33%) in group 1, but 0 (0%) in group 2 and 3. Two late death occurred all in group 1 with PVOA. Cardiopulmonary bypass time and aortic clamp time in group 3 were 91 min and 74 min respectively, which did not become longer than those in both group 1 and group 2. Interrupted suture technique does not make operating time longer than continuous running suture one. PVOA is one of the important factors predicting late operative result.(ABSTRACT TRUNCATED AT 250 WORDS)     

Placental alkaline phosphatase as a tumor marker for primary intracranial germinoma

A sensitive enzyme-linked immunosorbent assay (ELISA) was used in a retrospective study of placental alkaline phosphatase (PLAP) levels in serum, cerebrospinal fluid (CSF), and intratumoral cyst fluid in primary intracranial germinoma. The ELISA showed no cross-reactivity with intestinal alkaline phosphatase except in very high concentrations, after samples had been heat-treated. Three patients with germinoma were studied for serum PLAP levels and in all the levels were elevated (3.78, 0.52, and 2.11 IU/liter). Two of the germinoma patients were studied for PLAP levels in the CSF, and both had elevated levels (0.83 and 9.83 IU/liter). The intratumoral cyst fluid in one case of germinoma was tested for PLAP and the level was found to be very high (603 IU/liter). These PLAP levels decreased concomitantly with the reduction in tumor size during irradiation. Serum PLAP levels were measured in 40 control adult male individuals and in the CSF of 20 nonpregnant patients with subarachnoid hemorrhage. The upper normal limits were 0.20 and 0.11 IU/liter in the serum and the CSF, respectively. All PLAP levels measured in the serum of patients with various brain tumors were 0.18 IU/liter or less. This study strongly suggests that PLAP is a clinically useful tumor marker for primary intracranial germinoma.     

Induction of rat liver drug-metabolizing enzymes by tetrachloroethylene

The effect of tetrachloroethylene on Phase I and II drug-metabolizing enzymes in rat liver was examined. Rats were treated orally with tetrachloroethylene daily for five days, at doses of 125, 250, 500, 1,000 and 2,000 mg/kg. The higher doses (>500 mg/kg) of tetrachloroethylene induced the hepatic microsomal 7-pentoxyresorufin O-depentylase and 7-benzyloxyresorufin O-debenzylase activities associated with the CYP2B subfamily. 7-ethoxyresorufin O-deethylase activity was also induced about 2-fold compared with that of control rats at 500, 1,000, and 2,000 mg/kg dose levels of tetrachloroethylene. However, 7-ethoxycoumarin O-deethylase and 7-methoxyresorufin O-demethylase activities were increased significantly at only the 1,000 mg/kg dose level of tetrachloroethylene (1.4- and 1.5-fold). Although other cytochrome P450-mediated monooxygenase activities such as nitrosodimethylamine N-demethylase, aminopyrine N-demethylase and erythromycin N-demethylase were also induced by tetrachloroethylene, the relative induction to control activity was lower than those of 7-pentoxyresorufin O-depentylase and 7-benzyloxyresorufin O-debenzylase. Western immunoblotting showed that the levels of CYP2B1 and CYP2B2 proteins in liver microsomes were increased at doses of 1,000 and 2,000 mg/kg of tetrachloroethylene. In addition to cytochrome P450-mediated monooxygenases, there was significant induction of the Phase II drug-metabolizing enzymes, DT-diaphorase, glutathione S-transferase activities towards 1-chloro-2,4-dinitrobenzene and 1,2-dichloro-4-nitrobenzene, and UDP-glucuronyltransferase activities towards 4-nitrophenol and 7-hydroxycoumarin. The results indicate that tetrachloroethylene induces both Phase I (CYP2B-mediated monooxygenase) and Phase II drug-metabolizing enzymes (DT-diaphorase, glutathione S-transferase and UDP-glucuronyltransferase) in the rat liver.     

Balloon plasty for biliary strictures associated with choledochal cysts]

Balloon plasty with a Meditec balloon dilatation catheter was performed in thirteen patients who had choledochal cysts with intrahepatic biliary strictures. The age of the patients ranged from one to 28 years. Eleven were female, and two were male. The site of the biliary stricture was both the right and left hepatic duct in eight patients, the left hepatic duct in four, and the right hepatic duct in one. Balloon plasty was performed postoperatively through the fistula of the percutaneous transhepatic drainage tube in seven patients and during the operation in six. Dilatation was adequate in ten patients but insufficient in three. The preoperative imaging character of the biliary strictures in the successful cases was membranous stenosis of less than 2mm in length. In contrast, the strictures of the patients with insufficient dilatation were long stenoses of more than 5mm in length.     

Successful mitral valve repair for active infective endocarditis accompanied by anorexia nervosa

Infective endocarditis of the mitral area accompanied by anorexia nervosa is extremely rare. A 34-year-old Japanese woman presented with high fever and a heart murmur that had developed over the previous 2-month period. Echocardiography revealed mitral regurgitation and vegetation attached to the anterior mitral leaflet, which had markedly prolapsed to the left atrium. We removed the vegetation with a small part of the anterior mitral leaflet and successfully repaired the mitral valve. The patient showed good recovery, and the mitral regurgitation and left ventricular chamber size had satisfactorily decreased at 2 months after the operation.