Changes in rat liver Na+, K(+)-ATPase activity during long-term preservation at 4 degrees C.
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Biomedical subjects
Publications and source records attributed to T Tsunoda.
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Three patients with proven Budd-Chiari syndrome were examined with a duplex sonograph consisting of a real-time ultrasonograph and a pulsed Doppler flowmeter. In these cases, the pulsed Doppler analysis associated with the real-time imaging showed abnormalities in the direction of flow in the hepatic vein, communicating vessel between hepatic veins, and/or retrohepatic inferior vena cava, which were consistent with obstruction of hepatic venous outflow. With these findings, duplex sonography can be used to diagnose Budd-Chiari syndrome.
The natural killer (NK) cell mediated cytotoxicity to syngeneic tumor cells can be augmented by in vivo priming and subsequent in vitro challenge with the streptococcal preparation OK432. Supernatants of coculture of spleen cells with OK432 contained Interleukin 2 (IL-2) and Interferon (IFN), mainly IFN-gamma. As the anti-mouse IFN-gamma monoclonal antibody but not anti-mouse IFN-alpha antibody inhibited the induction of activated NK cells with OK432, the IFN-gamma participated in this response. The incubated spleen cells with IL-2 receptors increased with OK432 treatment by flow cytometry, and the NK cell and IFN activities of supernatants were also abrogated by the treatment with anti-mouse IL-2 receptor monoclonal antibody to block the interaction between IL-2 and these receptors of effector cells. By panning method, it was clarified that the incubated spleen cells with IL-2 receptors were responsible for the production of IFN-r. These results suggest that IL-2 plays a major role to induce the activated NK cells from murine spleen cells primed in vivo and subsequently challenged in vitro with OK432, by the production of IFN-gamma.
We had demonstrated that the NK cell mediated cytotoxicity of murine spleen cells could be augmented by in vivo prime and subsequent in vitro challenge with the streptococcal preparation OK432, and the cell surface phenotype of induced killer cells was Thy 1+, asialo GM1+, suggesting the activated NK cells (OK-NK cell). The culture supernatants of spleen cells with OK432 possessed the activity of IL-2 and IFN-gamma, and the IL-2 played a major role to induce the OK-NK cells via the production of IFN-gamma. In this study, we examined the effect of adoptive transfer of OK-NK cells on tumor-bearing mice. The mice were implanted SP2 myeloma cells intraperitoneally (i.p.), or C26 colon adenocarcinoma cells subcutaneously (s.c.) to make the models of peritonitis carcinomatosa or solid tumor, and the OK-NK cells were transferred i.p. or i.t., adoptively. By the adoptive transfer of OK-NK cells, the 92% of mice bearing SP2-tumor had be cured. The tumor growth of C26-solid tumor was inhibited, and the survival rate of mice bearing C26-tumor was increased, significantly. The intratumoral remnants of 125I-labelled OK-NK cells were 61.27 and 8% after intratumoral transfer, respectively. By multiple transfer of OK-NK cells the anti-tumor effect was more augmented than that of a single transfer. Thus we recognized the anti-tumor effect of adoptive transfer of OK-NK cells on tumor-bearing mice, and suggested that OK-NK cells could be useful for the therapy of cancer patients.
The present study shows that natural killer cell-mediated cytotoxicity of BALB/c mouse spleen cells to syngeneic tumor cells was augmented by in vivo priming or in vitro stimulation with the streptococcal preparation OK432. The augmentation of spleen cell cytotoxicity to syngeneic tumor cells by in vivo priming alone with OK432 was lower than that obtained by in vitro stimulation alone with OK432. When the murine spleen cells primed in vivo with OK432 were rechallenged in vitro with OK432 at various intervals, the natural cytotoxicity was more strongly enhanced than that seen with in vitro stimulation alone. The cell surface phenotype of killer cells activated with OK432 was Thy1+ and asialo GM1+, suggesting the activated natural killer cell. Mice were transplanted with syngeneic colon adenocarcinoma cells, and primed in vivo with OK432, and then their spleen cells were subsequently challenged in vitro with OK432. These cells displayed a strong cytotoxic activity not only to the transplanted adenocarcinoma cells but also to other syngeneic tumor cells.
The natural-killer(NK)-cell-mediated cytotoxicity to syngeneic tumor cells can be augmented by in vivo priming and subsequent in vitro challenge with the streptococcal preparation OK432. Supernatants of cocultures of spleen cells with OK432 contained interleukin-2 (IL-2) and interferon (IFN), mainly IFN-gamma. As the anti-(mouse IFN-gamma) monoclonal antibody but not anti-(mouse IFN-alpha) antibody inhibited the induction of activated NK cells with OK432, the IFN-gamma participated in this response. The enhancement of NK cell activity and production of IL-2 were partially inhibited by the pretreatment of spleen cells with mitomycin C or irradiation, and were completely abolished by pretreatment with actinomycin D. The IL-2 activity after treatment with various metabolic inhibitors ran parallel to the NK activity in a system augmented with OK432. The activity of incubated spleen cells with IL-2 receptors was increased by OK432 treatment, and the NK cell and IFN activities of supernatants were also abrogated by the treatment with anti-(mouse IL-2 receptor) monoclonal antibody, to block the interaction between IL-2 and these receptors of effector cells. The panning method clarified that the incubated spleen cells with IL-2 receptors are responsible for the production of IFN-gamma. These results suggest that IL-2 plays a major role in inducing the activated NK cells from murine spleen cells primed in vivo and subsequently challenged in vitro with OK432, by the production of IFN-gamma.
This study attempts to define early carcinoma of the extrahepatic bile duct through a study of 11 patients whose carcinomatous invasion did not extend to the outer layer of the bile duct. The patients were divided into the following 3 groups, namely; a mucosa group comprised of 3 patients, a fibromuscular layer group comprised of 5 patients, and an adventitia group comprised of 3 patients. None of the patients had any lymphnode metastases. Histological characteristics were determined according to infiltrative growth (INF alpha, beta, gamma), lymphatic invasion (ly), venous invasion (v) and perineural invasion (pn). In the mucosa group, INF alpha was observed in 2 patients, while ly, v, and pn factors were all negative. In the fibromuscular layer group, INF beta was seen in 3 patients, ly was positive in 2 patients, while v, and pn factors were negative in all patients. In the adventitia group, INF gamma was found in 2 patients, and ly, v, and pn factors were positive in all patients except for 1 in whom v was negative. Death from recurrence occurred in all the adventitia group patients and in 1 other patient. Early carcinoma of the extrahepatic bile duct could therefore be defined at present, as being carcinoma confined to within the mucosa and fibromuscular layer.
Among the various benign biliary tract diseases, intrahepatic lithiasis is the most refractory condition to treat surgically. Recently, endoscopic treatment (mainly cholangiofiberscopic lithotomy) has been more and more frequently employed. A nationwide survey by questionnaire was conducted in 1985 to clarify the exact status of the current therapies for intrahepatic lithiasis in Japan. A total of 143 institutions (33.4%) responded to our questionnaire, and 2614 cases over a 10-year-period were collected and analyzed. Operation alone was performed in 53.8%, operation plus endoscopic treatment in 38.6%, operation plus dissolution therapy in 5.5%, operation plus endoscopic treatment and dissolution therapy in 0.04% and endoscopic treatment alone in 2.1%. The most common treatment was surgery. This was employed in 97.9% of all the patients, but endoscopic treatment was added in 40.7% of the cases to extract stones mainly intra- and/or post-operatively. Dissolution therapy was carried out occasionally, but with poor results. Conducting both adequate surgical biliary drainage and cholangiofiberscopic lithotomy may result in a marked improvement in the treatment of this intractable disease.
The author introduces the concept of the Tsunoda Test. Different from conventional psychological experiments, the Tsunoda test is considered to measure the function of a sensory-motor system named automatic switching mechanism, which is believed to exist in the subcortical brainstem region. This mechanism automatically selects verbal and nonverbal sounds from processing by the right and left cerebral hemispheres according to physical acoustic characteristics. Subconscious motor and sensory responses play a vital role in our conscious activities, and the Tsunoda Test is directly applicable to an integral motor-sensory mechanism in the brainstem. The Tsunoda Test, which combines the motor modality with an auditory test, is beneficial for understanding the hitherto little known functions of the subconscious central brain. The concept of this Automatic Switching Mechanism closely overlaps the centrencephalic "automatic sensory-motor mechanism" hypothesized by W. Penfield from a vast number of clinical studies.
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Although surgical resection has been the mainstream treatment for carcinoma of the pancreas, the operative results have been so disappointing that most surgeons in western countries have given up performing the resectional procedure. On the contrary, Japanese surgeons have never abandoned their dream of surgical treatment as a cure for the disease. Therefore, more and more aggressive procedures have been performed. Our operative results have not so remarkably ameliorated, but we have become knowledgeable on the pathological features of the carcinoma and believe that the best procedure for carcinoma of the head of the pancreas is a pancreatoduodenectomy with extensive dissection of regional lymph nodes and retroperitoneal tissue, and that surgery itself can not cure the disease but multimodality treatment should be established. Two hundred cases with carcinoma of the pancreas in which cystadenocarcinoma and islet cell carcinoma were excluded, were encountered from 1969 to 1987 in our department. Of 200 cases, only 48 cases underwent resection. Resection was divided into curative and non-curative resection according to macroscopic findings and pathohistological examination of the resected specimen. In cases of curative resection group, the average survival period of cases which underwent multimodality treatment was much longer than that without any adjuvant treatment. However, in cases of noncurative resection group, average survival period of cases with multimodality treatment was almost the same as that without adjuvant therapy. Therefore, multimodality treatment should be applied for curatively resected cases in order to obtain better results. Radiation therapy, especially intraoperative radiation therapy is considered to be a promising alternative modality of extensive retroperitoneal dissection. Hepatic metastasis was found postoperatively in about 27 percent of the resected cases. It seems that this type of recurrence occurred by migration of malignant cells from the tumor into the portal vein due to operative manipulation during surgery. Therefore, intraoperative infusion of an anticancer agent through the portal vein is mandatory, and preoperative and postoperative adjuvant chemotherapy should be considered.
Reports of 35 long-term more than five years survivors after resectional surgery which was performed for carcinoma of the pancreas from 1966 to 1980 were collected from major institutions in Japan and analyzed. Male to female ratio was 0.94:1 and average age was 56 years old. In 34 of the 35, the tumor was located at the head of the pancreas, 32 received pancreatoduodenectomy and two underwent total pancreatectomy. One patient with carcinoma of the tail received distal pancreatectomy. There was no correlation between the size of tumor and the postoperative prognosis. It seems that lymph node metastasis is not an obstacle to long postoperative survivals when they are removed, and also invasion to the pancreatic capsule shows no relationship to prognosis. However, there were no definite or severe invasions to the retroperitoneal tissue, nor to the portal venous system in the 35 patients at all. It is considered that invasion to the retroperitoneal tissues and to the portal venous system may be the most influential factor to the postoperative prognosis.
Arterial intimal thickening and thrombosis of the pancreatic artery has frequently been found in Watanabe heritable hyper-lipidemic (WHHL) rabbits. Three of the 20 rabbits used in this study showed histopathological findings such as intra- or inter-lobular fibrosis with lymphocytic infiltration, acinar degenerative changes, ductular proliferation and small ductal dilatations which were identical to those of human chronic pancreatitis. These findings were observed in discrete areas clearly demarcated from normal pancreatic parenchyma and adjacent to parenchymal necrosis. These discrete areas were developed just peripheral to regions of necrotic or inflammatory obstruction of the pancreatic duct, which might have been caused by parenchymal necrosis due to severe ischemia. The stasis of pancreatic juice in the ductal tree may result in such findings in the WHHL rabbit. Fat replacement of pancreatic parenchyma was observed in 17 of the 20 WHHL rabbits, and was classified into two types, diffuse and massive. Massive fat replacement may occur from fat necrosis and intra-lobular parenchymal necrosis. Vascular alterations and secondary ischemia in the pancreas is one of the most important factors involved in the pancreatic lesions present in the WHHL rabbit.