The present study was conducted to determine the concomitant immunity in cancer patients by culturing lymph node cells obtained from various cancer patients with the primary cultured tumor cells derived from human cancer and the following results were obtained. 1. The primary cultures were conducted with 42 cases of gastric cancer, 12 of mammary cancer, 8 of cancerous thoracic fluid, 5 of cancerous ascites, 2 of metastatic hepatoma, 2 of thyroid cancer and 7 others. Among them there were 29 cases where the sufficient number of free cells were obtained by the same type of culture so that there were enough viable tumor cells attached on the culture vessel wall to harvest. 2. Effects of autochthonous lymph nodes on human primary cultured cancer cells: From the total of 22 cases comprising 9 cases of gastric cancer, 6 of mammary cancer, 2 of metastatic hepatoma, one of thyroid cancer, 2 of cancerous thoracic fluid and 2 of cancerous ascites, 30 series of cytotoxicity tests were conducted by mixing each of them with autochthonous lymph node cells mainly prepared with lymph nodes obtained at surgical operation. During the mixed culture for the period of 24 hours to 72 hours the cases where the autochthonous lymph node cells had shown anti-proliferative effect on the primary cutured cells amounted to 12/30 cases (70%), and those that showed a proliferative effect instead amounted to 1/30 cases (3.3%). 3. Effects of autochthonous lymph nodes according to their sites on human primary cultured cancer cells: Considering the sites of tumors, the lymph nodes collected were roughly divided into the regional lymph nodes and distant lymph nodes, and looking at their anti-proliferative effect 7/13 cases (54%) of the regional lymph nodes and 14/17 cases (82.4%) of the distant lymph nodes had shown the anti-proliferative effect. 4. Effect of allogeneic lymph nodes on the primary cancer cells derived from human patients: There were 30 lines of mixed cultures of allogeneic lymph node cells and the human primary cultured cancer cells, and of them 11/30 cases (36.7%) showed anti-proliferative effect. By dividing lymph nodes according to cancer patients and non-cancer patients 8/16 cases (50%) in the former had anti-proliferative effect while 3/14 cases (21.4%) in the latter group. From these findings it may be said that there is concomitant immunity established in human cancer and lymph nodes act inhibitorily on tumor. Moreover, most cases having larger tumors are in the terminal stage of cancer, and there can be observed a decrease-disappearance of immunity of regional lymph nodes in such cases.
On the administration of methylcholanthrene (MCA) to mice there can be observed a decrease in the plaque forming cells (PFC) from early stage, and in the post-administration week 5, at the time considered to be of precancerous stage the decrease in PFC number is most marked, being at the minimal level of 55.6% as compared with that of the control (untreated mice). In other words, the administration of MCA reduces the PFC number of spleen cells in mice and it markedly suppresses the immunological activity of normal mice. This indicates that MCA is appreciably involved in the immunity to carcinogenesis. On the other hand, the activity of allogeneic inhibition in the precancerous stage is maintained during the period between MCA administration and the time of cancer development. However, the allogeneic inhibition activity decreases by 8 weeks after MCA administration, the time when the tumor has grown to the size macroscopically visible. This finding suggests that the activity of the allogeneic inhibition is associated more with the proliferation rather than with oncogenesis.
In order to study the carcinogenicity and its mechanism of N-Nitrosobutylurea (NBU), 10 week old RF mice was abministrated with 0.025% NBU water solution as drinking water every day. 1. Thymoma was induced after an average latency of 93 days and average rate of the tumor induction was 88.6%. Both sexes were equally susceptible. 2. Histologically thymoma was lymphosarcoma and other lymphatic organs also showed lymphosarcoma. However leukemic signs were not found in the peripheral blood and by clinical tissue culture. 3. Leukemia virus was not found in the electron microscpic observation and cell free transmission of leukemia was unsuccessfull.
The induction and development of tumors by chemical carcinogens are explained by the correlation of the tumor antigen and host. Especially the immunity of the host is regarded as important. Therefore, the immunological effect on the host was studied. 1. The serum protein analysis showed an increase of β2-globulin due to an increase of transferrin and decrease of γ-globulin suggesting a decline of immunity. 2. The plaque forming cells of the spleen and thymus four days after a single i.p. injection of 0.2ml of 20 percent sheep red cells were decreased from the early stage of administion of NBU and markedly decreased already before the induction of tumors and were very rare during the tumor growth. 3. The hemolysin and hemagglutinin titers four days after a single i.p. injection of 0.2ml of 20-percent sheep red cells also showed similar changes.
In an attempt to study auto-immune phenomenon in the course of development of chronic hepatitis, the sensitization with homologous liver and Freund's complete adjuvant as well as the passive transfer of sensitized spleen cells were conducted with rats. As a result it was found that by the sensitization with homologous liver and Freund's complete adjuvant a marked round cell infiltration and the stellate cell reaction were observed in Glisson's capsule and sinusoid of the liver as compared with control group, and with a few cases there was observed lymphoid focus in Glisson's capsule. By the passive transfer of sensitized spleen cells, there could be detected the infiltration of round cells in Glisson's capsule and sinusoid of the liver and in a few cases liver cell necrosis mainly of piecemeal necrosis. In the subsequent observations on blood anti-liver antibody, intratissue γ-globulin as well as the localization of anti-liver antibody, there could be recognized no significant correlations to the above-mentioned histological changes of liver, but in the culture of sensitized rat peripheral lymphocytes conductes in the presence of liver antigen there was observed a significant blast-like transformation as compared with control group. From these experimental results with rats it seems that the lymphoid focus and piecemeal necrosis observable in Glisson's capsule of the liver in human liver diseases can also be said fairly safely to be the histological expression of auto-immune phenomenon.
This report is concerned with histological and electronmicroscopic studies on a spontaneous mammary carcinoma of AKR mice which are known to be high leukemic and low cancer strain. Followings are the conclusions obtained. 1) The spontaneous mammary carcinoma was type B adenocarcinoma according to Dunn's classification. The histology was similar to those frequently observed in mammary carcinoma of high cancer strain of mice such as C3H, RIII, and DBA mice. Electronmicroscopic studies revealed many type A virus particles around the cytoplasmic vacuoles or free in the cytoplasm, and numerous type B virus particles In the acinar spaces. In addition, a few type B virus particles were observed in the cytoplasmic vacuoles and in the intercellular spaces. Morphology, distribution, and formation process of these virus particles were similar to those observed in mammary carcinoma of high cancer strain of mice and some of low cancer strain of mice. These results indicate that there exist “milk factor” in low cancer strain of mice as well as in high cancer strain of mice and that the factor can induce mammary carcinoma even in low cancer strain of mice when hormonal and other environmental factors are abequate. 2) Serial electronmicroscopic observations of the original and serially transplanted mammary carcinoma of AKR mice disclosed a gradual decrease in numbers and only a few immature type B virus particles were observed after the 21st generation. These findings were ascribed to the sarcomatous transformation and loss of acinar spaces observed during the serial transplantation of the original mammary carcinoma.. 3) The original mammary carcinoma of AKR mice harbored numerous type A and type B virus particles. Type C particles, however, were hardly observed. In tissue culture cells derived from the tumor, in contrast, numerous type C virus particles were observed and type B virus particles were hardly found. These findings were considered to suggest that there is an interference between type B and type C virus particles in AKR mice.
This report is concerned with morphological studies on tissue culture cells derived from a spontaneous mammary carcinoma and it's serially transplanted tumors of AKR mice. Four lines of tissue culture cells were obtained. A-419 and A-319 lines of cells were obtained from the fourth transplant generation of the tumor (adenocarcinoma), A-600 line of cells were obtained from the 26th transplant generation of the tumor (sarcomatous), and A-162 line of cells were from the adenocarcinoma produced by back-transplantation of primary culture cells of A-419 line cells to AKR mice. These four lines of tissue culture cells showed similar morphology and distribution, mixed growth of both epithelial cells and fibroblastic cells. Back-transplantation of primary culture cells of A-419 and A-319 lines to AKR mice produced adenocarcinomas, but A-319 line cells of later passages (28th, 29th, 31st, and 35th passage) and A-600 line cells produced sarcomas when transplanted back to AKR and C3Hf mice. Two mechanisms have been proposed to explain the sarcomatous transformation; 1) transformation of carcinoma cells to sarcoma cells and 2) malignant change of interstitial connective tissue cells during serial passages of the culture cells. The second mechanism was considered to be most probable in the present case.
This report is concerned with electronmicroscopic studies on tissue culture cells obtained from a spontaneous mammary carcinoma and it's serially transplanted tumors of AKR mice. Numerous type C virus particles were observed in A-419 line, A-319 line, and A-162 line of tissue culture cells. These particles showed a gradual decrease during the serial passages in vitro. This finding is interesting in view of the fact that numerous type A and B particles but no type C particles were observed in the tumors from which those tissue culture cells were derived. In contrast, mature type B particles were observed in A-600 line tissue culture cells, whereas only a few immature type B particles were observed in the 26th transplant generation of the tumor from which A-600 line cells were derived. The results obtained suggest a possible interference between type A and B particles and type C particles. Bioassays of tissue culture fluids from A-419, A-162, and A-600 lines induced neither leukemia nor mammary carcinoma in test mice.
We encountered a 24-year old female with a swelling and severe pain in the hypogastric region as her main complaints and another 32-year old male with hypogastric pain persisting for several years as main complaint. On the x-ray examinations of the gastrointestinal tract of these two cases, both of them were suspected of Crohn's disease, and they were subjected to surgical operation. As to a result of pathohistological examinations they were definitively diagnosed as case of Crohn's disease. As to the definition of Crohn's disease opinions differ even today, but we presented of our findings on these two cases as well as our review on the x-ray pictures on Crohn's disease available in the literature.
Serum α1-acid glycoprotein (α1-AG) and α1-antitrypsin (α1-AT) levels were measured in 30 controls, 57 patients with nonmalignant disease and 249 patients with malignant neoplasm of various sites and stages. An almost parallel increase of these glycoproteins was observed in patients with advanced cancer except hepatoma, but in cases with localized lesion these serum levels remained normal. In 85 patients with lung cancer and 49 with stomach cancer, considerable relationship was observed between the serum levels of these glycoproteins and degree of progression of cancerous lesions. Therefore, it seems that these glycoprotein levels are a relible index for staging malignant diseases. In Hodgkin's disease, however, there was no relationship between these serum levels and its clinical stage, but these glycoprotein levels in B cases of Hodgkin's disease were significantly elevated than in A cases. Evaluation of these glycoproteins would serve as a diagnostic means in patients with hepatomegaly and/or jaundice, since in patients with hepatoma α1-AG levels are decreased and α1-AT levels are elevated, in patients with metastatic liver cancer both of them are significantly elevated and in cirrhosis of the liver α1-AG levels are clearly decreased and α1-AT levels remain normal.
Serial determinations of serum α1-acid glycoprotein (α1-AG) and α1-antitrypsin (α1-AT) were performed in 43 cases with lung cancer and 25 cases with stomach cancer during therapeutic procedures, and in 31 courses of remission induction-chemotherapies of 23 cases with malignant lymphoma. These studies reveal that changes in serum α1-AG levels during chemotherapy would be an index to the efficacy of chemotherapeutic agents for malignant neoplasms because it has been shown that α1-AG levels changed in intimate relation to neoplastic processes in almost all the cases of lung or stomach cancer. Especially, in malignant lymphoma, changes in α1-AG levels during the clinical course showed such a close relation to vicissitudes of lymphadenopathy that serial determinations of this glycoprotein was regarded as a reliable index not only for the efficacy of chemotherapy but also for the early detection of relapse prior to the manifestations of clinical symptoms. On the other hand, changes in α1-AT levels did not correlate to the progression of canecrous lesions in almost half the cases recieving various chemotherapeutic agents and corticosteroids. It was considered that these agents, especially corticosteroids, might be directly concerned with metabolism of this glycoprotein. In patients with lung or stomach cancer who did not obtain any clinical improvement during chemotherapy, significant correlation was observed between α1-AG as well as α1-AT levels prior to chemotherapy and their life spans. Therefore, it was possible to set up a regression line of life spans against these glycoprotein levels and life spans of ineffective cases to chemotherapy could be estimated roughly according to this regression line.
1. Guanidino compounds, taurocyamine, glycocyamine, α-N-acetyl-L-arginine, β-guanidinopropionic acid, γ-guanidino-β-hydroxybutyric acid, γ-guanidinobutyric acid, γ-hydroxyarginine, arginine and γ-guanidinobutyramide, were analysed by the automatic guanidino compound analysing system, based on liquid chromatography with an ion exchange resine LCR-1 (or Aminex A-5) column and Sakaguchi reaction. 2. The concentrations of taurocyamine, glycocyamine, γ-guanidinobutyric acid and arginine in rodent brain tissue were determind. On the other hand, five unknown peaks with positive Sakaguchi reaction were observed in the rabbit brain. 3. Guanidino compounds level in liver, kidney, serum and urine of rabbit were determined and compeared with in brain. 4. It was observed that γ-guanidinobutyric acid in the rabbit brain was increased, and on the contrary, taurocyamine, glycocyamine and arginine were decreased during convulsion induced by Metrazol injection. 5. Arginine and taurocyamine levels in the El-mouse were tended to increase atfer having the convulsive disposition.
Spindle-like afterdischarges evoked by stimulation of ventrolateral thalamic nucleus and spontaneous spindle waves were analized to investigate the electrophysiological mechanism of cortical synchronized activities in man as well as in cat. In man, three positive and three negative waves, namely I-P, I-N, II-P, II-N, III-P and III-N, were observed as cortical evoked responses after single stimulation of the ventrolateral thalamic nucleus. And IV-P and IV-N were observed after the stronger stimulation which could provoke augmenting response with the repetitive volley. Later components of evoked cortical responses were investigated in cat immobilized under local anesthasia. Recording electrole was located on the anterior sigmoid gyrus. As the intensity of the thalamic stimulation was increased, afterdischarges of the negative waves, which appeared with long latency (about 200msec.), increased in number and developed into spindle-like pattern with notches on afterdischarges. The long latencied negative wave in cat and IV-N in man were considered to correspond to Lehtinen's “precursor of the evoked spindle activity”. It has been already reported by Miyamoto that IV-N was supposed to play an important role in augmenting response in man. Close relationship was indicated between augmenting response and spindle-like afterdischarges. Futhermore, the similarities of the pattern between spindle-like afterdischarges following thalamic stimulation and spontaneous spindle waves in cat, and attenuation of ipsilateral spontaneous spindle waves after destruction of the ventrolateral thalamic nucleus in cat as well as in man were also observed. From these facts these cortical synchronized activities, namely AR, spindle-like afterdischarges and spontaneous spindle waves were considered to be brought by similar neuronal mechanism with some varieties of synchronization ascribed to arousal levels under influences of activities of the ventrolateral thalamic nucleus. On the other hand, spindle-like afterdischarges and spontaneous spindle waves in cat were analized for investigating their waxing and waning phenomena. Notches were observed on each waves. When the wave grew with maximal amplilude in a train of spindle, the notch of the wave became obscure. The phenomenon was considered that the notch was synchronized with the wave, forming maximal amplilude of the wave in a train of spindle. In other words, mechanism of this phenomenon was supposed to be explained as a beat of two rhythmic activities slightly different in frequency.