Two 8-month-old and two 4-month-old male beagle dogs received 250 ml of 150 microgram/ml solution of N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) and 2% Tween 60 mixed with a pellet diet twice a day for 8 months as the same methods used for mongrel dogs in our first report [Juntendo Medical Jouranl 19, 579-583 (1973)]. Gastric carcinomas with distant lymph nodes metastases occurred in three beagle dogs except for one died from anesthesia at the endoscopy. Metastases to the liver were observed in two beagles. In the most long-lived beagles, peritonitis carcinomatosa with ascites and metastases to the liver, lungs, bones, and skin were found. Main gastric tumors were located at the subcardia in two dogs (elevated tumor in dog No. 6, ulcerated tumor in dog No. 8), but in dog No 7 at the angulus (ulcerated tumor). Histologically, carcinomas were composed of poorly differentiated adenocarcinoma, signet-ring cell carcinoma, tubular adenocarcinoma, and undifferentiated adenocarcinoma. In all of three dogs which developed adenocarcinoma of the stomach, Stewart's criteria were completely satisifed. Using our methods the target organ is limited only to the stomach, without any sarcomatous lesion of the intestines.
In order to clarify the pathogenesis of rickets in preoperative patients with extrahepatic biliary atresia, we evaluated baseline serum 25-OHD and 1,25(OH)2D levels and correlated serum 25-OHD levels with increase in age and season of birth in 16 preoperative patients. Further, parenteral vitamin D2 tolerance tests were performed in 5 cases. Serum 25-OHD and 1,25(OH)2D levels were significantly lower than those in 15 normal controls. There was a negative correlation between the serum 25-OHD levels and increase in age. The patients born during the winter had lower serum 25-OHD concentrations than those born in summer. The mean value of increased 25-OHD levels after the parenteral vitamin D2 tolerance tests did not differ from that of 6 controls. Since there was no impairment of vitamin D 25-hydroxylation, the reduction in serum 25-OHD may therefore be mainly due to disturbed intestinal vitamin D absorption. It was also concluded that season of birth and increase in age are pathogenic factors in the etiology of rickets in preoperative patients with extrahepatic biliary atresia.
The interplay of Nrp-1 and Sema3A shown in our results may lead to a better understanding of interaction between sinusoidal remodeling and SECs during liver regeneration.
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