Autoradiographic Analysis of Radiolabeled Anti-carcinoembryonic Antigen Monoclonal Antibody CEA102 in Colorectal Cancer Using Computed Radiography

Anti-carcinoembryonic antigen monoclonal antibody (MAb) CEA102 was produced by immunization with purified CEA and the specific accumulation of radiolabeled CEA102 in colorectal cancers was investigated by autoradiography of surgical specimens using Fuji Computed Radiography (FCR). Five patients with colorectal cancer were injected intravenously with ¹³¹I-labeled intact CEA102 or its F(ab')₂. Primary tumor and liver metastases were successfully detected by external scanning with a gamma camera in 4 cases. Autoradiographic study of the surgical specimens using FCR showed predominant localization of ¹³¹I-labeled CEA102 in primary tumors and liver metastases in all cases. Even a small liver metastasis (0.5 cm) was clearly visualized in the autoradiogram by FCR. The pixel distribution curves of the density of the respective tissues in the autoradiograms by FCR showed the heterogeneity of the distribution of administered radiolabeled MAb in individual tumors, but the density of the tumors was higher than that of the normal tissues. In the quantitative distribution analysis of CEA102, the uptake of the primary tumor (mean 1.10%ID/kg) was ten-fold greater than that of the normal colon mucosa (mean G.10%ID/kg). These results revealed that the application of MAb has great potential in radioimmunodetection as well as in antibody-directed therapy.     

The effects of leg-cooling on blood lactate disappearance following supramaximal exercise.

In order to clarify whether leg-cooling after supramaximal treadmill exercise will change lactate disappearance rate from venous blood, blood lactate, calf blood flow, and skin temperature were determined in cold application and non-cold application recovery. In the cooling experiments, both legs were cooled with ice packs for 23 min during recovery. The skin temperature was significantly lower in the cold application as compared with the non-cold application. However, no significant difference was found in the blood lactate and/or calf blood flow between cold and non-cold conditions. In addition, there was no significant difference in the slope of regression line (blood lactate/blood flow) between cold and non-cold applications. These results suggest that no significant difference in the blood lactate between cold and non-cold applications could be explained by the lack of difference in the blood flow between cold and non-cold applications.     

Kinetic study of glomerular epithelial cells associated with segmental glomerular sclerotic lesions with adhesion in spontaneously diabetic WBN/Kob rats

Background We previously found that glomerular epithelial cells play an important role in the formation of adhesive lesions. Glomerular sclerotic lesions develop after the inital adhesive lesions. Methods Two series of experiments were done with spontaneously diabetic WBN/Kob rats. These rats develop segmental glomerular sclerotic lesions with aging. The first series of experiments was intended to clarify the kinetics of glomerular cells on progressive glomerular damage in these rats. The second series of experiments was designed to study the relationship between proliferation (judged by % bromodeoxyuridine-positive cells) of glomerlar epithelial cells and sclerotic lesions with adhesions. Results In the first series, rats having increased proteinuria showed segmental glomerular sclerotic lesions with adhesions. At the same time, increased labeling indices of tuft cells and epithelial cells of Bowman's capsule were observed. In the second series, no significant increase in the labeling indices of tuft cells with sclerotic lesions was observed, compared to tuft cells without sclerotic lesions. In sclerotic lesions with adhesion, bromodeoxyurdine-positive cells were observed that were not distinguishable as podocytes or epithelial cells of Bowman's capsule. The highest labelling index was noted in the epithelial cells of Bowman's capsules with sclerosis. Conclusion This study shows that the proliferation of glomerular epithelial cells (mainly epithelial cells of Bowman's capsule) occurs in glomerular sclerotic lesions with adhesions.     

Clinical and epidemiological aspects of enteritis due to Salmonella hadar. II. Environmental contamination by Salmonella hadar in Shizuoka Prefecture--studies on the feasibility of reducing S. hadar infection]

A systematic examination was performed for environmental food contamination by Salmonella in poultry farms, broiler chickens, broiler processing plants and meat on the market. Salmonella was isolated from 219 of 1197 samples and the serotypes showed a wide distribution. (Table 1-1). S. hadar accounted for 37.1% (96) of all isolations (259). The contamination rate of broiler chickens on arrival at broiler processing plants is relatively low. However, in the broiler processing plants, containers, processing machinery, cooling water and slaughters were highly contaminated by Salmonella, S. hadar being the most prominent serotype in the plants. 64% of chicken meat on the market was contaminated by Salmonella, S. hadar being the second most prominent serotype. 11% of the pork and none of the beef or horseflesh was contaminated by Salmonella. These results indicate that poultry is the main source of S. hadar infection in humans. However, no S. hadar was isolated from cultures of 119 samples of feed for chickens from each delivery (Table 1-1). Thus, as the main source of infection by S. hadar of broiler chickens, an association with the feed seems to be ruled out. S. hadar was isolated at three of 18 poultry farms within Shizuoka Prefecture. Follow-up studies were performed at the three poultry farms which revealed that in two of them, Salmonella was completely eradicated on completion of disinfection. In the other one farm, which is still being disinfected, various strains of Salmonella including S. hadar still survived. We conclude that the main cause of the problem is the magnification of contamination of Salmonella-free material during the process at the broiler processing plants.(ABSTRACT TRUNCATED AT 250 WORDS)     

Endogenous tumor necrosis factor exerts its protective function intracellularly against the cytotoxicity of exogenous tumor necrosis factor.

Based on the findings that expression of endogenous tumor necrosis factor (enTNF), which is not present in TNF-susceptible cells, was generally observed in TNF-resistant cells and that TNF gene transfection gives rise to TNF resistance, the assumption was made that enTNF may be a protective protein against the cytotoxicity of exogenous TNF. However, it remains unknown whether the protection by enTNF is exerted in an intracellular or extracellular (autocrine) manner. We therefore transfected a nonsecretory human TNF gene (pTNF delta pro) into highly TNF-sensitive mouse tumorigenic fibroblasts (L-M cells) and investigated their TNF susceptibility. The transfectants expressed enTNF which was not secreted into the medium and acquired an appreciable degree of resistance to exogenous TNF. A significant increase in the manganous superoxide dismutase level was also noted in the transfectants. These findings suggest that enTNF exerts its protective function intracellularly by inducing manganous superoxide dismutase production.     

Human placental glutathione transport mechanism

The placental transport mechanism of glutathione (GSH) was investigated using microvillous membrane vesicles prepared from human term placenta. Using (3H-glycine)-labeled-GSH, it was clarified that GSH in the extravesicular compartment of placental microvillous membranes was rapidly degraded by gamma-GTP (gamma-glutamyltranspeptidase) and resulting amino acid, and 3H-labeled-glycine was actively transported via a sodium cotransport system. AT-125 treated microvillous membrane vesicles almost entirely lost its gamma-GTP activity, and showed intact GSH transport. Using AT-125 treated microvillous membrane vesicles, it was revealed that GSH was transported across the microvillous membrane as an anion via a membrane potential-dependent mechanism. These results indicated that gamma-GTP which existed in microvillous membrane played a role in GSH metabolism and that intracellular GSH was translocated out of the syncythiotrophoblast cell into the maternal blood space via a specific carrier in microvillous membrane because the GSH concentration was higher in intracellular than extracellular and extracellular membrane potential was positively charged.     

Surgical treatment of myasthenia gravis associated with Graves's disease]

During past 30 years, we experienced 253 patients who underwent surgery for myasthenia gravis. Among these patients, 9 were associated with Graves' disease. No patients had thymoma. Five patients underwent thymectomy after they had become euthyroid by medical treatment, though four patients required subtotal thyroidectomy before thymectomy. One patient developed myasthenic crisis following thyroidectomy and was treated with respirator for 5 days. But thymectomy was performed without myasthenic crisis in these four patients between 25 days and 60 days after thyroidectomy. They have been doing well and no see-saw phenomenon was presented. Thymectomy is safe and effective even in the patients with Graves's disease, and we recommend to perform it after they become euthyroid by medical or surgical treatment.