Strain Difference in Effects of Ethanol Treatment on Fetal Development in C57BL and DBA Mice

Pregnant C57BL and DBA mice were treated with i. p. injection twice of 25% ethanol (3.97 g/kg × 2), four hours apart, on day 7, 8, 9, 10, 11, 12 or 13 of gestation. They were killed on day 18 of gestation, and the fetuses were examined for external and skeletal malformations. In order to determine the blood ethanol levels, nonpregnant animals were treated with the same dose of ethanol and then killed at 0.5-16 hours after injection. Fetal mortalities of DBA mice were higher than those of C57BL mice. The body and brain growth retardations were severer and the incidence of malformations was higher in C57BL mice than in DBA mice. The most frequently observed malformations were microphthalmia and digital malformations in C57BL mice, and open eyelids in DBA mice. Blood ethanol reached the maximum level within half an hour after the second injection in both strains, and was significantly higher in DBA mice than in C57BL mice 2–15 hours after the second injection. It is difficult to explain the strain difference of embryotoxicity between C57BL and DBA mice on the basis of only the difference in blood ethanol level in the present study.     

The Third Nationwide Survey in Japan of Vitamin K Deficiency in Infancy

The occurrence of hemorrhagic disease due to vitamin K (VK) deficiency beyond the neonatal period has come under investigation in Japan. In 1980 the 1st nationwide survey was conducted in Japan by Nakayama and others [1], and was followed by the 2nd nationwide survey in 1985 by Hanawa [2]. The present survey was designed to further monitor the incidence of this disease in Japan during the 3-year period from July 1985 to June 1988. Questionnaires were sent to 1,315 hospitals having more than 200 beds, located throughout Japan. Responses were received from 775 hospitals, for an answer rate of 58.9%. The total number of reported cases was 175, including 129 idiopathic type, 28 secondary type and 18 near-miss type. In this survey it was revealed that the incidence rate of the idiopathic type of vitamin K deficiency in infancy (VKDI) has decreased remarkably, to about one-fourth that reported in the first survey. The declining incidence rate of VK deficiency in Japan is considered to be the result of ever more widespread prophylactic administration of VK during the neonatal period, as most occurrences of VK deficiency in infancy are preventable by prophylactic administration of VK from the neonatal period. However, in 16 cases of the idiopathic type of VK deficiency found in the present survey, VK had been administered at least once during or after the neonatal period. This shows the heterogeneity of this condition.     

A metastatic model of human colon cancer constructed using cecal implantation of cancer tissue in nude mice

COL-2-JCK, a human colon cancer xenograft line able to be transplanted into nude mice, was implanted in the subserosal layer of the cecum, either as cancer tissue or as a single cell suspension. When cancer tissue was used for the cecal implantation, 100% extensive local tumor growth and a high incidence of metastases to the regional lymph nodes, peritoneum, liver, and lung was observed. In contrast, when the cell suspension of this line was injected into the cecal wall, no metastases were observed, with significantly reduced local tumor growth. The use of cancer tissue maintaining the original cancer tissue structure is therefore considered imperative for allowing full expression of the biological characteristics of cancer cells. This nude mouse model using the cecal implantation of cancer tissue should thus prompt further study on the biology of human colon cancer.     

Neuronal degeneration in amyotrophic lateral sclerosis is mediated by a possible mechanism different from classical apoptosis

In order to determine the potential role of apoptosis in the degeneration in amyotrophic lateral sclerosis (ALS), we correlated the morphological characteristics of the remaining neurons in the spinal cord with the results of in situ DNA fragmentation detected by terminal transferase-mediated deoxyuridinetriphosphate (dUTP)-biotin nick-end labeling (TUNEL) in 17 cases of ALS, five age-matched control cases, six aged control cases, and three disease control cases with spinal cord lesions. The remaining neurons were classified into five categories: normal appearing, chromatolytic, degenerative, atrophic, and inclusion laden. We measured the areas of the per©karya, the nuclei, and the nucleoli of the neurons in these categories. The areas of perikarya, nuclei, and nucleoli in the postero-posterolateral neurons of the ALS cases were significantly decreased compared with those of the age-matched controls. The nucleolar and nuclear areas of even normal-appearing neurons from the ALS cases were significantly decreased compared with those from the age-matched controls, suggesting that nuclear and nucleolar shrinkage in normal-appearing neurons in ALS is an early change in this disease. However, the frequency of TUNEL-positive neurons in the normal-appearing, degenerative, atrophic, or inclusion-laden neurons in the spinal cord of the ALS cases was not significantly elevated compared with those in the age-matched, aged, or disease controls. No apoptotic bodies were detected by electron microscopy in the ALS spinal cords examined. Our results suggest that neuronal degeneration in ALS involves a certain mechanism different from classical apoptosis. We hypothesize that classical apoptosis may be a terminal event of neuronal degeneration in ALS, even though classical apoptosis has a role in the disease processes of ALS.     

Clinical aspects of congenital cystic dilatation of the common bile duct in adults

We reviewed the data for 155 patients with congenital cystic dilatation of the common bile duct (CCDB; Alonso-Lej Type I) treated at our institute in the past 12 years. Our definition of CCDB was segmental enlargement of the common bile duct or enlargement involving the proximal bile duct, visualized on cholangiograms. CCDB was subclassified as infant or adult type cyst, based on the extent of the enlargement and the clinicopathologic findings. The former is typically an enlargement of the common bile duct or an enlargement involving the common hepatic duct, while the latter is an enlargement of the entirety of the extrahepatic ducts or involves the intrahepatic bile ducts. Of the 155 patients, 5 (including 1 child) had infant type cysts and 150 (including 1 child) had adult type cysts; 125 patients had benign CCDB (3 with infant type cyst) and 30 exhibited CCDB biliary malignancy (2 with infant type). Anomalous arrangement of the pancreaticobiliary ductal system (AAPB) and congenital biliary stricture were frequently associated with CCDB and these features played an important role in the presenting symptoms of CCDB: AAPB was detected in 100 of the 155 patients, and stricture in 51. AAPB caused disturbance of the passage of bile from the terminal bile duct to the duodenum and cholestasis in the enlargement, with reciprocal regurgitation of bile into the pancreas and pancreatic juice into the bile duct, and the AAPB appeared to precede obstructive jaundice, acute pancreatitis, or biliary malignancies. Stricture was observed at one to all of six sites in the hepatic hilum. Intrahepatic stones were seen in 30 patients, and intrahepatic bile duct cancer was seen in 8 patients; in all these 8 patients, the cancer was associated with primary intrahepatic stones.     

A Rubella Epidemic in Sasebo, Japan in 1957, with Various Complications

Though the rubella vaccination programme for adolescent girls was introduced in Japan in 1977, rubella epidemics have occurred repeatedly. Also in Sasebo, Japan in 1987, we experienced various complications as follows: encephalitis (five cases), meningitis (three), thrombocytopenic purpura (four), vascular purpura (four), hemolytic anemia (two), pneumonia (eight), protein-losing gastroenteropathy (one), multiple organ disorder with encephalitis, purpura, myocarditis, hepatic and renal dysfunction (one), and congenital rubella syndrome (CRS: three). Disorders ranging over multiple organs seem to occur in acquired as well as congenital rubella infection. The incidence of encephalitis was estimated to be 1: 1600 cases of rubella and two of five cases were apparently serious. Though the strategy for preventing rubella has been directed only against CRS, we should note the various and severe complications with acquired rubella infection, and should adopt two-stepped protection: vaccination of young children of both sexes and of adolescent girls.     

Venous invasion as a prognostic factor in colorectal cancer

Venous invasion as a prognostic factor was evaluated in 124 patients with colorectal cancer. By classifying the patients as having either negative to mild invasion or moderate to marked invasion, a significant correlation was found between the degree of venous invasion and clinicopathological variables such as lymphatic invasion, lymph node metastasis, liver metastasis, and DNA ploidy. Significantly more favorable survival was seen in those with a lower degree of vascular invasion; however, of the six prognosticators analyzed by Cox's proportional hazard model, the only significant factors were depth of invasion and DNA ploidy. Although venous invasion showed no significance, it is still considered a valuable prognostic indicator that is easy and economical to perform.     

Mechanism of Synergistic Cytotoxic Effect between Tumor Necrosis Factor and Hyperthermia

We previously reported that recombinant human tumor necrosis factor (rhTNF) and hyperthermia had a synergistic effect against tumors, in vitro and in vivo. We have now investigated the mechanism of this synergy by measuring the lysosomal enzyme activity and hydroxyl radical production of L-M cells treated with rhTNF and/or hyperthermia. A synergistic activation of lysosomal enzyme and the induction of hydroxyl radical production in L-M cells treated with both rhTNF and hyperthermia was observed. A synergistic cytotoxic effect was observed when rhTNF and hyperthermia were combined, and was inhibited by the addition of a reactive oxygen scavenger, dimethyl sulfoxide or bipyridine. The results show that the augmenting effect of hyperthermia on lysosomal enzyme activation and induction of hydroxyl radical production by rhTNF plays an important role in the synergistic cytotoxic effect.     

Sweet's Syndrome with Small Cell Carcinoma of the Lung

We report a 59-year-old male with Sweet's syndrome who developed small cell carcinoma of the lung one year after the initial diagnosis. To the best of our knowledge, this is the first report of Sweet's syndrome in conjunction with lung cancer. In cases of Sweet's syndrome, a search for not only hematologic disorders but also for solid tumors should be made.