Effects of benzimidazoles on mouse and rat limb bud cells in culture

Benzimidazoles exhibited an inhibitory action on the chondrogenesis in a mouse limb bud cell culture system; further, nitro and chloro groups at the 5 position in 2-(2-pyridyl)benzimidazole were found to be potent substituents. However, 2-(2-pyridyl)benzoxazole and 5-methoxy-2-(2-pyridyl)benzothiazole exhibited no inhibitory action under our experimental conditions. Thus, imidazole NH proton seemed to be important in the inhibitory action in the mouse cell system. The concentrations of thiabendazole (TBZ), 5-hydroxy-TBZ (5-HY-TBZ) and N-methyl-TBZ necessary to reduce the amounts of cartilage proteoglycan by 50% (TP50) were estimated to be about 0.35, 0.25 and 0.70 mM, respectively, in the rat limb bud cell culture system. The TP50 of TBZ and 5-HY-TBZ in the rat cell system were 3- to 4-fold higher than those in the mouse cell system.     

A well-differentiated hepatocellular carcinoma within adenomatous hyperplasia

A 37-year-old male was admitted to hospital for jaundice and ascites. An ultrasonogram revealed a hypoechoic mass located in the right anterior inferior segment. A needle specimen of the liver was taken, and its biopsy led to a histological diagnosis of a hepatocellular carcinoma. The patient subsequently underwent an operation wherein it was found that the resected tumor that was taken was not clearly demarcated from the cirrhotic parenchyma. The histological diagnosis was an adenomatous hyperplasia. In a portion of this adenomatous hyperplasia, highly consistent hepatic cells and pseudogland formations were seen, confirming the diagnosis of a well-differentiated hepatocellular carcinoma within an adenomatous hyperplasia.     

Acute blasticidin S poisoning

Blasticidin S is an effective fungicidal aminocylonucleoside antibiotic against a rice blast disease. We presented the first 4 reported cases of acute poisoning from ingesting blasticidin S for suicidal attempts. Three of the patients were fatal. The symptoms observed in the patients included vomiting immediately after ingestion and severe, persistent, watery diarrhea. The toxic effects of blasticidin S were noted in ectodermal tissues including the skin, conjunctiva, cornea, and intestine. Massive loss of intestinal fluid resulted in progressively pronounced hypotension associated with tachycardia. The treatment of choice for the poisoning consists of intravenous fluid administration and the management of body water and electrolyte balance.     

Long-term tissue distribution and steady state activity ratios of 232Th and its daughters in rats after intravascular injection of Thorotrast

To estimate the absorbed dose in the critical organs of Thorotrast patients, it is necessary to know not only the distribution and concentration of 232Th but also its daughter nuclides in the body. The present investigation was undertaken in order to clarify the long-term 232Th tissue distribution and steady state activity ratios between subsequent daughters in the critical tissues using about 30 Wister male rats, as a basis for estimating absorbed doses. The tissue distribution of thorium was examined by means of an autoradiography of the whole body and/or the gamma-ray spectrometry at various times during 2 to 24 months following injection. The concentrations of daughter nuclides in tissues were determined by repetitive gamma examination over a period from 1 hr to 35 days after being sacrificed. The data indicate (1) that approximately 90% of injected Thorotrast is retained in the body for a prolonged period, but about 50% of radium and 10% of radon produced from thorium are eliminated from the body, (2) that the mean steady state activity ratios of 224Ra and 212Pb to 228Th for liver are 0.56 and 0.28, and 0.54 and 0.16 for spleen, 0.58 and 0.82 for lungs, respectively, and (3) that the parent 228Th is translocated to the bone.     

Establishment and characterisation of human carcinoembryonic antigen transgenic mice

We have produced human CEA transgenic mice which were found to express CEA mRNA in all tissues. By immunoblot analysis using anti-CEA polyclonal antibody, we also detected CEA protein in all tissues. However, the molecular size of CEA in the brain was different from that in other tissues, although the mRNA size was same and no deletion nor rearrangement was detected at the DNA level. Immunohistochemical analysis of the lung and the colon showed that the expression sites were the bronchial epithelial cells of the lung and the columnar epithelial cells of the colon. Interestingly, the expression of CEA protein in the transgenic mice was polarised to the luminal side of epithelial cells similar to the normal CEA expression in human tissues. We also detected cell surface expression of human CEA on thymocytes and spleen cells and CEA expression was greatly reduced by the phosphatidylinositol-specific phospholipase C (PI-PLC) treatment.     

Evaluation of drug disappearance from nasal cavity by the deposit method.

In order to evaluate antiallergic intranasal formulations, the rates of drug disappearance from rat nasal cavity were estimated by the deposit and perfusion methods. The deposit method, which estimates changes in the amount of residual drug in the nasal cavity following washout of the deposited drug over time after application, yielded a good correlation between apparent disappearance rate constant and the combination of lipophilicity and molecular weight. Since the deposit method can be used only with delivery of small amounts of drug to the nasal cavity, the physiological characteristics of the nasal membrane readily affect drug disposition in tests performed with it, and adsorptive drugs such as parabens exhibited rapid disappearance. Doses used clinically for intranasal administration are usually small, and in the case of antiallergic formulations, it is important to maintain the drug concentration in the nasal mucous membrane. The deposit method should be useful for evaluating intranasal antiallergic drug formulations.     

Acute interstitial pneumonia following surgery for primary lung cancer.

OBJECTIVE: Although acute interstitial pneumonia is a life-threatening complication following surgery for lung cancer, the cause and risk factors for acute interstitial pneumonia remain unknown. We conducted this study to determine the characteristics of acute interstitial pneumonia after pulmonary resection and to identify the risk factors for this disease. METHODS: We experienced 16 (2.0%) cases of acute interstitial pneumonia among 822 patients who underwent pulmonary resection for primary lung cancer over a period of 12 years. We performed a retrospective analysis of these patients, comprising the patients' background, the operative procedure, the radiographic characteristics and the prognosis. RESULTS: In all patients, the shadow appeared within 1 week after the operation. Twelve patients required mechanical ventilatory support due to the development of respiratory failure. The site of the tumor (right side), preoperative radiation or chemotherapy, pneumonectomy, blood transfusion, and intraoperative complication were independent risk factors for the incidence of acute interstitial pneumonia (P=0.001, 0.0484, 0.0012, 0.0002, 0.0003, respectively) in the multivariate analysis. Nine of the 16 patients died due to respiratory failure, resulting in a mortality rate of 56.3%. The maximum amount of lactate dehydrogenase (LDH) in the operative death patients was significantly higher than that in the survivors (472+/-138IU/l vs 257+/-79IU/l, respectively, P=0.0031). CONCLUSIONS: We concluded that in order to reduce the incidence of acute interstitial pneumonia, it is necessary to perform careful postoperative management for patients who are male, have right lung disease, have undergone preoperative chemo or radiation therapy, or have undergone pneumonectomy.