抗原および抗ヒトIgEに対する好塩基球の反応性. 1.好塩基球数の変化

Blood basophils in subjects with bronchial asthma migrate from blood stream into local allergic reaction sites after inhalation of antigen into airways. The phenomena can be observed by changes in number of basophils in the peripheral blood. The peripheral basophil count is at a normal level in non-attack stage of asthmatics as in healthy subjects. The basophil count increases in pre-attack stages, and decreases during attack stages. These findings suggest that number of basophils changes in close relation to asthma cycle, and that by observing number of basophils in the peripheral blood, it is possible to detect near future attacks. The decrease in number of basophils and histamine release by stimulation with antigen and anti-IgE can be observed in vitro in whole blood and basophils separated by density gradient centrifugation and by counterflow centrifugation elutriation. The decreased number of basophils in the peripheral blood represents migration of the cells into local allergic reaction sites.気管支喘息では,気道への抗原吸入後,好塩基球は末梢血よりアレルギー反応局所へと遊走する｡この現象は,末梢血中の好塩基球数の変動により観察することができる｡気管支喘息患者の好塩基球数は,非発作時には健常人とほぼ同じで正常範囲内にあるが,発作前段階で増加し,発作出現とともに減少する傾向を示す｡これらの所見は,好塩基球が喘息発作と密接な関連を持ちながら変動すること,そして,これらの変動を観察することにより,近い将来の発作を予知することが可能であることを示唆している｡抗原あるいは抗ヒトIgE刺激による好塩基球数の減少およびヒスタミン遊離は,全血法あるいは濃度勾配法やcounterflow centrifugation elutriation法により分離された好塩基球を用いてin vitroで観察することができる｡末梢血中の好塩基球数の減少は,好塩基球がアレルギー反応局所へと遊走したことを示している

Studies on the treatment of malignant tumors with fibroblast-inhibiting agent III. Effects of chloroquine on human cancers

A fibroblast-inhibiting agent, chloroquine, used in the treatment of animal tumors led to a reasonably good result, and this approach was extended to the treatment of human cancers. Of histologically proven 54 cases, the drug was effective in 38, ineffective in 15, and unknown in one. It proved to be effective in all the patients who were treated for over 2 months with exception of terminal patients. Of the various malignant tumors treated, excellent therapeutic effects were obtained in patients with carcinoma of the lung and bladder. In the cases where the drug was effective there were a decrease of the size of tumors, fall of serum lactic dehydrogenase, increase of necrosis, inhibition of the stroma, as well as improvement of the symptoms and general condition. As to the mechanisms of the drug action, it would be necessary to consider of its anti-inflammatory and humoral effects upon the host in addition to its inhibitory action on the stromal connective tissue of cancers. The present chloroquine treatment appears to have its indication in inoperable cases, and pre- and post-operative cases, and for the prevention of reccurrence of tumors. Studies are currently in progress in our laboratory to discover more potent fibroblastinhibiting agents and on the combined chemotherapy of chloroquine and other anti-turnor agents. We are indebted to the Department of Urology of our University for the generosity to allow us to use the clinical data on patients with cancer of the urinary bladder.</p

Iron metabolism of in­testinal mucosa in various blood diseases

For the investigation of iron metabolism in the intestinal mucosa in various&#12288;blood diseases, intestinal biopsy (duodenum) was performed on 10 healthy controls&#12288;and 35 cases with various blood diseases. The following are&#12288;the results&#12288;of the studies on distribution of stainable&#12288;iron, amounts of non-hemin iron in the&#12288;biopsied materials, and iron uptake of the intestinal epithelial cells.&#12288;1) An evaluation of distribution of stainable iron by Berlin&#12288;blue reaction&#12288;showed none or very mild degree, if any,&#12288;inhealthy controls, an increase in&#12288;aplastic anemia,&#12288;pernicious anemia, some of leukemias and in iron deficiency anemia following iron therapy, and a decrease in&#12288;idiopathic hypochromic anemia, anchylostomiasis anemia,&#12288;anemia with cancer, myxedema, hemolytic anemia,&#12288;and in&#12288;some of leukemias. Some of anemia with cancer, however,&#12288;showed an&#12288;increase of a certain degree. In iron absorption tests, no changes were found other than a very mild increase in aplastic anemia. 2) Non-hemin iron was 70-112&#947;/g in healthy controls, increased in aplastic anemia approximately to 100-200&#947;/g, ranging 40-130&#947;/g in leukemia, and decreased in idiopathic hypochromic anemia and in anemia with cancer ranging 30-60&#947;/g and 30-50&#947;/g respectively. Amounts of non-hemin iron and serum iron or sideroblasts show a fair correlation. The fractionation of nonhemin iron in aplastic anemia didn't show any difference in relationship of each fraction from healthy controls despite the increased amount in the former. 3) A radioautographic evaluation of iron uptake by intestinal epithelium was performed by our device for evaluation of intestinal absorption capacity. The iron uptake was mild in healthy controls, almost none in aplastic anemia, and marked in iron deficiency anemia where it was decreased approximately to the level of healthy controls following iron therapy. 4) The intestinal tissue iron showed a series of changes similar to those of iron present in the serum or erythroblasts, and the non-hemin iron in the intestinal mucosa is inversely correlated with iron uptake of epithelium and is considered to regulate the absorption according to its amount.</p

The iron content of gastric juice: in relation to the cause of idiopathic hypochromic anemia

Non-hemin iron content in gastric juice was examined in 46 patients with various blood diseases, especially idiopathic hypochromic anemia and in 26 healthy controls. 1. The iron content in gastric juice was found to be 290 &#956;g/ dl in healthy controls, a lower value of 110 &#956;g/ dl in idiopathic hypochromic anemia and a higher value of 550 &#956;g / dl in aplastic anemia. These values were in a close correlation with serum iron or sideroblasts. 2. In idiopathic hypochromic anemia there was also a close correlation between the iron content in gastric juice and hemoglobin. In the course of treating idiopathic hypochromic anemia (stage of recovery of anemia) the iron content in gastric juice showed a marked increase over the value in healthy controls as well as a transient increase after an intravenous iron tolerance test. This condition may be interpreted as an &#34;iron-losing anemia&#34;. Iron excretion of gastric mucosa in various blood diseases and its changes in the course of treating idiopathic hypochromic anemia in relation to the cause of this anemia were discussed.</p

Studies on the treatment of malignant tumors with fibroblast-inhibiting agent. I. Fibroblast-inhibiting action of chloroquine

The effects of chloroquine on the growth and morphology of fibroblasts in tissue culture, and in vivo granulomas were investigated. As the result, the drug was shown to have a potent action to inhibit fibroblast growth, which has led to a possibility of its clinical use to patients with malignant tumors.</p

Study on sideroblasts as a determi­nation method of the erythropoietic function of bone marrow

With the purpose to study sideroblasts as a means of diagnosing blood diseases and to pursue the metabolism of non-hemin iron in erythroblasts we investigated sideroblasts (erythroblasts containing iron granules stainable by Prussian blue) under various erythropoietic conditions in the human and rabbits, and obtained the following results: 1. In blood diseases the proportion of sideroblasts in the case of low erythropoietic condition is higher and in the case with accelerated erythropoietic condition and of iron deficiency it tends to be lower than that in normal persons. Further, obtaining sideroblastogram and sideroblast ratio (S. r.) from the classification of Types I, &#8545;, and &#8546; according to the iron granule content, it has been proven that abnormal conditions can be clearly distinguished from the normal, indicating that sideroblasts are closely associated with erythropoietic function. This is proven to be a far superior method for the diagnosis as well as for the prognosis of blood diseases than the determination of serum iron. 2. In experimental anemic rabbits the relationship of sideroblasts to the condition of erythropoietic function is still more clearly recognized, and it has been found that variations in the sideroblast count is dependent upon the condition of the equilibrium between the iron supply from serum iron and the iron utilization controlled by the erythropoietic function. 3. In addition, in the iron-treated rabbits under various erythropoietic conditions we have been able to confirm that there are a certain mechanism and a limitation to the iron intake by erythroblasts, and that erythroblasts take essentially three steps of metabolic processes, namely, intake, retention, and utilization of iron almost simultaneously, in the latter half of the maturation stage.</p

Studies on the treatment of malignant tumors with fibroblast-inhibiting agent IV. Effects of chloroquine on malignant lymphomas

Eleven cases of malignant lymphomas were treated with a fibroblast-inhibiting agent, chloroquine, and of these, one case of lymphosarcoma, two of acute and chronic lymphocytic leukemia, respectively, and two of giant follicle lymphoma showed regression of the enlarged lymph nodes and also of the enlarged spleen in some of the splenomegalic patients. In contrast, the drug proved ineffective in two cases of reticulum cell sarcoma and Hodgkin's disease, respectively. The side effects of the drug were minimal, and three of the 11 cases complained of nausea, anorexia or palpebral ptosis, which disappeared by decreasing the drug dosage or combining ATP preparation. The tissue culture study of biopsied lymph nodes from lymphocytic leukemia showed inhibition of the growth zone in a medium containing chloroquine indicating a possibility of the drug action not only upon the stromal tissue but also upon the parenchymal tumor cell.</p

Studies on the treatment of malignant tumors with fibroblast-inhibiting agent. II. Effects of chloro­quine on animal tumors

Based on our original concept, a fibroblast-inhibiting agent, chloroquine, was used against various animal tumors. Among transplanted animal tumors, the drug was most effective on relatively connective tissue-rich Bashford and Brown-Pearce tumors, as reflected by prolongation of life span, inhibition of tumor growth, inhibition of lowering of liver catalase activity, improvement of iron metabolism, increase of tumor necrosis, inhibition of connective tissue formation, and decrease of acid mucopolysaccharide. On the other hand, it was of little advantage in Ehrlich, Yoshida and MH134 tumors which contain little connective tissue, except for a decrease of the amount of ascites and ascites tumor cells in the former two tumors. These results indicate that chloroquine suppress the growth of the tumors relatively rich in connective tissue. This effect of chloroquine appears to be due to the primary attack of the stromal connective tissue of tumors being followed by the degeneration of tumor cells, though its probable anti-tumor activity by the indirect effects through its anti-inflammatory and systemic humoral activities should be taken into consideration.</p

気管支肺胞洗浄液中リンパ球増多と患者年齢およびIgE系アレルギー反応との関連について

The proportion and number of lymphocytes in the airways were analyzed in 15 patients with a high proportion of lymphocytes in bronchoalveolar lavage (BAL) fluid (more than 30%) and in 17 patients with less than 20% of BAL lymphocytes. 1. Both atopic and nonatopic asthma patients with a high proportion of BAL lymphocytes were aged more than 50 years. In contrast, the age of patients with less than 20% of BAL lymphocytes ranged widely, from 29 to 63 years, in the two asthma types. 2. Age at onset of the disease, serum IgE levels, and ventilatory function test were not related to the proportion of BAL lymphocytes. 3. In patients with a high proportion of BAL lymphocytes, the mean proportion of these cells was 47.3% in atopic patients and 36.4% in non-atopic patients, i. e., there was no significant difference between the two asthma types. The absolute number of BAL lymphocytes in these patients was significantly higher in atopic (5.62×10(6)) than in nonatopic asthma (0.77×10(6)) (p<0.01). These findings show that an increased number of lymphocytes in the airways is clearly related to patient age and IgE-mediated allergic reaction.気管支肺胞洗浄(BAL)液中のリンパ球頻度が30%以上の15例および20%以下の17例の気管支喘息患者を対象に,BAL液中リンパ球頻度と年齢およびIgE系反応との関連について検討を加えた｡1.BALリンパ球が高頻度(30%以上)を示す症例は,アトピー型,非アトピー型を問わず,50才以上の年齢層に多い傾向が見られた｡一方,BALリンパ球20%以下の症例の年齢は,29-63才まで幅広く分布していた｡2.発症年齢,血清IgE値,換気機能とBAL液中リンパ球頻度との間には関連は見られなかった｡3.BAL液中リンパ球頻度が高い症例では,アトピー型では平均リンパ球頻度は47.3%,非アトピー型では36.4%であったが,両群間には有意の差は見られなかった｡しかし,BAL液中のリンパ球の絶対数は,アトピー型(5.62×10(6))において,非アトピー型(0.77×10(6)) に比べ有意に高い値を示した(p<0.01)。これらの結果は,気道内リンパ球の増加は,患者年齢とIgE系反応と密接に関連していることを示唆している

ラット腹腔肥満細胞のCa(2+) influxおよびヒスタミン遊離に対する抗アレルギー薬アゼラスチンの抑制効果について

The effect of antiallergic agent, azelastine, was examined in immunogical secretory process of mast cells. 1. Azelastine significantly inhibited (45)Ca uptake by mast cells stimulated by antigen, and the maximum inhibition was attained at a concentration of 50 μg/ml showing approximately 30.5 % inhibition. 2. Azelastine also inhibite the release of histamine from mast cells by antigen. The maximal inhibitory rate was 38.1%. The effect of azelastine on (45)Ca uptake and histamine release was dose-dependent, and compatible at employed cocentration of the agent. 3. Tachpylaxis to azelastine was not found in this experimental system.抗原刺激時の,ラット腹腔肥満細胞のCa(2+) uptakeおよびヒスタミン遊離に対する,抗アレルギー薬アゼラスチンの抑制効果について検討を加えた｡その結果,1.アゼラスチンは抗原刺激時の肥満細胞のCa(2+) uptakeに対して濃度依存性の抑制効果を示した｡2.同様に,抗原刺激時の肥満細胞からのヒスタミン遊離に対しても,濃度依存性の抑制効果を示した｡3.アゼラスチンの再暴露による抑制効果の減弱傾向は見られず,アゼラスチンでは　tachyphylaxisは観察されなかった