In vitro study of the mechanisms of senescence acceleration.

Accelerated senescence can be considered to be an aging process that occurs after development and maturity and is characterized by a higher rate of increase in the degree of senescence than seen in the "normal senescence process." We devised culture methods to determine precise population doublings in cultured fibroblast-like cell lines and subsequently compared the aging process, in vitro, in cell lines established from either accelerated senescence-prone or- resistant strains of mice to obtain evidence of accelerated aging. Fibroblast-like cell lines were established from the dorsal dermis of the newborn accelerated senescence-prone mice of the SAMP11 strain and from accelerated senescence-resistant mice of the SAMR1 strain. All cell lines from both strains showed senescence as evidenced by a crisis in growth; then were immortalized. However, in cell lines from the SAMP11 strain, this growth crisis occurred more rapidly and at earlier population doubling levels than in cell lines from the SAMR1 strain. The methods and materials should aid in the elucidation of mechanisms linked to accelerated senescence in mice.

Accelerated aging of dermal fibroblast-like cells from the senescence-accelerated mouse (SAM): acceleration of changes in DNA ploidy associated with in vitro cellular aging.

Accelerated changes in the DNA ploidy associated with in vitro aging were examined in fibroblast-like cells isolated from the dorsal dermis of newborn SAMP11 (accelerated senescence-prone, short-lived) mice, and were compared to changes observed in cell lines from SAMR1 (accelerated senescence-resistant, long-lived) mice. Flow cytometric analysis of the DNA content in confluent cells and chromosome analysis in mitoses revealed that the diploid cells were being replaced with tetraploid cells until a growth crisis; thereafter, hypotetraploid cells became predominant, accompanied by immortalization. The number of mitoses decreased as the crisis ensued, then increased. Although these changes were observed in the cell lines from both strains of mice, the changes occurred more rapidly and at earlier population doublings in the cell lines from the SAMP11 mice. These results suggest that the cell lines from SAMP11 mice might have higher susceptibility to factors that cause polyploidization, including oxidative stress.

[Chemotherapy of peritonitis with particular reference to concentrations of sulbenicillin in human ascites (author's transl)].

Twenty-seven patients with peritonitis to whom a drain was applied were given sulbenicillin (SBPC), a broad-spectrum antibiotic, which has so little hepatic and renal toxicity that massive doses may be feasible, and examination was made as to its therapeutic effects and concentrations of the antibiotic in the ascites. Daily dosage of SBPC was 10g in two divided doses in most cases given by the intravenous infusion. Medication was continued for 3 approximately 15 days. The highest daily dosage was 20g and the largest total dosage reached 190g, but there was no adverse reaction except for one case of a slight anemia. Peritonitis complicated appendicitis, adnexitis, duodenal ulcer perforation, intestinal obstruction or trauma as its primary disease. No difference in the therapeutic effect existed among the primary diseases. The response to SBPC treatment was excellent in 8 of the 27 patients and good in 17. Two patients failed to respond to the therapy. When SBPC was given just before operation, the SBPC concentration in ascites obtained at operation was 112 microgram/ml in 2 cases. The SBPC concentrations in ascites were examined following intravenous infusion of 5g over an hour, and a peak concentration of 94.7 microgram/ml was obtained at the completion of infusion (an hour after the start of infusion), which gradually decreased thereafter. In the ascites excreted from the drain after operation, a high concentration of 12.7 approximately 90.2 microgram/ml (mean: 51.7 +/- 7.7 microgram/ml) was obtained on the day after the operation day, but the concentration was lower thereafter. The SBPC concentrations in ascites were compared as regards the sites of drainage (Winslow's foramen, ileocecum and Douglas' fold), but no particular difference was observed. The SBPC concentrations in ascites after operation were in inverse proportion to the alleviation of peritonitis. They were higher when the inflammation was severer.

[Experimental and clinical studies on the intestinal anastomosis and reconstruction of the alimentary tract].

Healing process of anastomosis and its procedure were studied in following points: Four-interrupted sutures anastomosis in the Wistar rats revealed recanalization without leakage in 64 out of 69. Lymphangial recanalization through the anastomosis was completed within 21 days after operation by Gambee' layer-to-layer anastomosis. While 8 weeks were required by everted or inverted anastomosis. Serosal surface of invaginated intestinal segment of which length corresponded to x1-x2 luminal diameter in the telescoping anastomosis was covered within 8 weeks by the proliferated mucosae of the both proximal and distal segments. Telescoping anastomosis was found to be useful to make an intestinal valve which worked just the same as ileocoecal junction. IVH and elementary diet were effective on the healing of anastomosis. According to the above mentioned findings, following operative procedures were recommended: Esophago-jejunal conduit duodenostomy following total gastrectomy. Choledocho-jejunal conduit duodenostomy with the intestinal valve as bile duct reconstruction. Construction of the intestinal valve and an artificial sphincter using rectus abdominis muscle fibers for ileostomy or short bowel syndrome. Endorectal pull-through operation for anterior-resection of the rectum as well as for radical treatment of Hirschsprung' disease.