臨床血液
Online ISSN : 1882-0824
Print ISSN : 0485-1439
ISSN-L : 0485-1439
24 巻, 9 号
選択された号の論文の18件中1~18を表示しています
第24回総会
教育講演
シンポジウムI 自己免疫性溶血性貧血の成因と治療をめぐる諸問題
  • 松橋 直
    1983 年 24 巻 9 号 p. 1150-1151
    発行日: 1983年
    公開日: 2009/01/26
    ジャーナル 認証あり
  • 尾崎 承一, 白井 俊一
    1983 年 24 巻 9 号 p. 1152-1160
    発行日: 1983年
    公開日: 2009/01/26
    ジャーナル 認証あり
    The spontaneous production of anti-erythrocyte autoantibodies (AEA) in New Zealand Black (NZB) mice and their hybrids has been suggested to be controlled by at least two genetic loci. A single dominant allele of NZB locus (A) determines the production of AEA, and the second locus regulates the expression of A gene. The present studies were designed to determine the nature and the location of the second locus, using NZB, C57BL/6, their F1, F2 and the F1×NZB backcrosses. The incidences of positive AEA were 100, 0, 0, 17 and 51% in these mice, respectively. This finding is in keeping with the idea that a single dominant allele of C57BL/6 locus (M) modifies (suppresses) the expression of A gene of NZB strain. M/m locus is loosely linked to Mup-1 locus on chromosome 4, and the gene order was M/m: Mup-1: Gpd-1.
    We also analysed the effect of M/m locus on other autoimmune traits, and found that the gene action of M/m locus is specific for AEA production, low hematocrit and splenomegaly and is unrelated to spontaneous production of anti-DNA antibodies, anti-retroviral gp 70 antibodies and natural thymocytotoxic autoantibodies. The positive AEA was associated with the high serum IgM concentration in (C57BL/6×NZB) F1×NZB backcrosses. It was not determined whether M/m locus might also control the serum IgM concentration.
  • 藤原 道夫
    1983 年 24 巻 9 号 p. 1161-1165
    発行日: 1983年
    公開日: 2009/01/26
    ジャーナル 認証あり
  • 外山 圭助, 池本 久美子, 今井 道代, 萩原 董, 大竹 皓子, 加野 象次郎
    1983 年 24 巻 9 号 p. 1166-1172
    発行日: 1983年
    公開日: 2009/01/26
    ジャーナル 認証あり
    Although cold agglutinin is sometimes elevated in the serum of patients with Mycoplasma pneumoniae infection, severe hemolytic anemia rarely occurs.
    We investigated immunologically cold agglutinin in a patient with severe cold agglutinin hemolytic anemia (Hb 5.0 g/dl) associated with mycoplasmal pneumonia. Complement-fixing antibody titer against M. pneumoniae was 1:512, and cold agglutinin titer 1: 16, 384 in the serum at the initial hemolytic stage. Cold agglutinin eluted from autologous erythrocytes of the patient revealed monoclonal IgM (κ) and anti-I specificity. This IgM was found to react with mycoplasmal antigen in comlement-fixing test again M. pneumoniae. Immunoglobulins such as IgM and IgG were isolated by using affinity chromatography from the patient's sera in the hemolytic and convalescent stage. In isolated IgM, cold agglutinin and complement-fixing antibody titer against M. pneumoiniae were elevated to 1:800 and 1:400 respectively at the hemolytic stage, followed by lowering considerablly at the convalescent stage.
    These findings support that the cold agglutinin in mycoplasmal infection represents a cross-reaction between erythrocyte and M. pneumoniae.
  • β-ガラクトシダーゼ標識酵素免疫測定法による赤血球結合免疫グロブリン定量を中心として
    山田 英雄, 平野 明人
    1983 年 24 巻 9 号 p. 1173-1183
    発行日: 1983年
    公開日: 2009/01/26
    ジャーナル 認証あり
    A sensitive enzyme-linked immunoassay technique for the quantitation of red cell-bound immunoglobulins (IgG, IgA and IgM) was devised and applied to quantitating red cell-bound immunoglobulins in normal and pathologic states including autoimmune hemolytic anemia (AIHA) and other disorders. Red cells from normal subjects gave values (mean±1SD, ng/1010 red cells) of IgG 73.2±25.8, IgA 23.6±8.2 and IgM 14.3±7.5, respectively. Fifteen patients with AIHA had an increased level of red cell-bound immunoglobulins of three calsses: IgG 3114.2±3074.3, IgA 84.8±79.9, and IgM 398.9±540.6. The concentrations of red cell-bound IgG in AIHA patients correlated well with the reticulocyte percentage in peripheral blood and showed a rapid fall to a certain level after the initiation of steroid therapy, indicating that the amount of autoantibodies on red cells is one of the major determinants of the rate of hemolysis in vivo in AIHA. Young red cells, separated by Percoll density gradient centrifugation from the peripheral blood of AIHA patients, contained less red cell-bound IgG concentration than the old cells. It was also found that marrow erythroblasts from AIHA patients have very low binding capacity of IgG coated immunobeads in comparison to the high binding capacity of their peripheral red cells. These facts suggest that the antierythrocyte autoantibody in AIHA has less affinity to the membrane of young red cells. Red cell-bound immunoglobulin levels in Fisher-Evans syndrome, ITP, SLE, RA and IgG myeloma by this technique were also presented and their pathophysiologic significance in each disorder is discussed. The results obtained in this study gave us basis for clarifying physiologic as well as pathophysiologic significance of red cell-bound immunoglobulins in health and disease.
  • 鈴木 信也, 砂田 光俊, 満永 幹雄, 太田 善介
    1983 年 24 巻 9 号 p. 1184-1192
    発行日: 1983年
    公開日: 2009/01/26
    ジャーナル 認証あり
    In vitro interaction between peripheral blood monocytes and the antibody-sensitized human erythrocytes was studied morphologically and with the 51Cr release assay. IgG antibody-sensitized human erythrocytes (EA) were phagocytized easily by monocytes in vitro when incubated at 37°C for 60 min, but it was inhibited competitively by the addition of free IgG in the medium. Complement-coated erythrocytes, without IgG sentization, were bound by monocytes as rosette fashion but not ingested even after incubation at 37°C for 60 min. Chromium release assay revealed that the sensitized erythrocytes were killed extracellularly by monocytes and it was enhanced by the addition of Cytochalasin B. Simultaneous sensitization of EA with complement component (C 3) also enhanced the lysis by monocytes and overcame the inhibitory effect of fluid phase IgG. Complement-coated erythrocytes per se were not lysed by monocytes in vitro but significant 51Cr release was observed after the addition of Cytochalasin B. These finding suggested that the lysis of erythrocytes by monocytes occurred extracellularly by the release of lysosomal enzymes. Non-sensitized chromium-labelled erythrocytes, when incubated with non-labelled EA and monocytes, were not lysed by monocytes even though Cytochalasin B was added. It was suggested that the lytic action of lysosomal enzymes was effective to the erythrocytes directly attached to the monocyte surface through Fc or C 3 receptors but did not affect to the neighboring normal erythrocytes.
    Cytolytic activity of monocytes from patients with inflammatory diseases was enhanced compared to that of normal persons. Monocytes from patients with AIHA also showed enhanced capacity to phagocytize the autologous sensitized erythrocytes. The sensitization (arming) of monocytes with antierythrocyte autoantibodies seemed to be a factor responssible for this monocyte activation in AIHA.
  • 松本 昇, 石原 得博
    1983 年 24 巻 9 号 p. 1192-1197
    発行日: 1983年
    公開日: 2009/01/26
    ジャーナル 認証あり
    The red of the spleens from three patients with autoimmune hemolytic anemia and two with Evans' syndrome was examined by electron microscopy. In the cases in which splenectomy was done as the first choice of therapy, phagocytosis of sensitized red cells by the cordal macrophages was more frequent comparing to the cases which were given corticosteroids before the operation. At the early stage of erythrophagocytosis, intact-appearing red cells were observed within the phagocytic vacuoles of macrophages. As the intracellular digestion progressed, small, electron dense daughther vacuoles appeared around the initial erythrophagocytic vacuoles, which turned to be less dense and usually contained partially destructed red cell membrane.
    Partial phagocytosis or surface microfragmentation by the cordal macrophages was suggested as a possible mechanism of immune spherocytosis. However, this finding was rather infrequent and contribution of other mechanisms, such as membrane damage by lysosomal enzymes released from macrophages and metabolic conditioning in the splenic cord, must be considered.
    In addition to the unique anatomical structures of the red pulp, agglutination of red cells by antibodies and reduced deformability of immune spherocytes are responsible for the stagnation and hemoconcentration in the splenic red pulp, which ultimately promote immune adherence and phagocytosis of red cells by the macrophage.
  • 恒松 徳五郎, 小川 博遊
    1983 年 24 巻 9 号 p. 1198-1202
    発行日: 1983年
    公開日: 2009/01/26
    ジャーナル 認証あり
    Autoimmune hemolytic anemia (AIHA) is a disease characterized by the presence of anti-red cell autoantibody on red cells and, in about a half of the patients, in their sera. Shortening of the red cell survival in vito is due mainly to the enhanced phagocytosis by macrophage through Fc-receptors.
    Production of the autoantibody is resulted from organic or functional derangement of lymphocytes. Although the etiology of AIHA has not yet been clarified, the genetic and environmental factors are considered important in the derangement of the immune system.
    Corticosteroids have been widely and effectively used for treatment of AIHA as the first choice drug. As is well known, the drugs are not curative ones. Clinical and experimental efforts are being made toward developement of newer treatment which leads to cure of AIHA.
    1. It was shown that there was a marked decrease in suppressor function of T lymphocytes in a patient with AIHA. From the in vitro experiment, corticosteroids in certain concentrations showed the enhancing effect on concanavalin A (Con A) induced suppressor T lymphocyte. This was revealed in the assay system by measuring T lymphocyte proliferation in response to stimulation of non-T lymphocyte in mixed lymphocyte culture and B lymphocyte proliferation to poke weed mitogen. The suppressor enhancing effects are not long-lasting in vivo when corticosteroids are given patients with AIHA. A new treatment should be deviced to focus upon how to maintain longterm enhancement of suppressor T-lymphocyte.
    2. NZB/W F1 mice are model animals of human systemic lupus erythematosus. Abouta half of the mice develope the anti-red cell antoantibody and show positive Coombs'test. Fractionated electron beam irradiation of total 2,000 rad resulted in a marked prolongation of survival as compared with non-radiated controls. Few of the irradiated mice showed positive Coombs' test long after the irradiation. It was postulated that long-term maintenance of enhancement of suppressor T lymphocytes was obtained by the irradiation.
    3. Mycoplasma pneumonia is sometimes associated with hemolytic anemia of cold autoantibody type. Elimination of the mycoplasma using antibiotics such as tetracyclin and erythromycin leads to a complete cure of the hemolytic anemia. α-Methyl dopa is an antihypertensive drug which is known to cause, in some patients, Coombs' positive hemolytic anemia after long-term administration. Discontinue of the drug in the patients with hemolytic anemia brings a gradual improvement of anemia and, several months later, Coombs' test becomes negative. In the idiopathic AIHA of warm autoantibody type, it is postulated but not yet convincingly established that the environmental factors would invade into body and play a role in the developement of the disease. If this is true, the elimination of the factors out of body could lead to a complete cure of AIHA.
  • 小峰 光博, 須田 哲夫
    1983 年 24 巻 9 号 p. 1203-1213
    発行日: 1983年
    公開日: 2009/01/26
    ジャーナル 認証あり
    The current status of the therapeutic aspects and long-term clinical course of warm-type autoimmune hemolytic anemia (AIHA) was summarized. The data were derived from the patient materials which had been collected under cooperation of many major institutions and clinics by the Research Committee of Hemolytic Anemias (Chairman: Prof. Shiro Miwa, 1974∼1976) and that of Idiopathic Hematopoietic Disorders (Chairman: Haruto Uchino, 1977∼1982), the Ministry of Public Health and Welfare.
    A total of 185 patients (152 with idiopathic and 33 with symptomatic variety) was followed up for the respective average periods of 7.4 and 4.5 years. The overall mortality during these periods was 28% for idiopathic and 58% for symptomatic AIHA. The survival fraction of the former declined steadily until an apparent plateau was reached at 65% after 10 years from onset. This indicates that potentially serious problems distribute over the wide time span ranging from onset to the order of at least 10 years. After prolonged clinical course (mean: 9.4 years), 43% of patients with idiopathic AIHA were off treatment and the rest were kept under the continued maintenance therapy, of which 67% was with minimal doses of corticosteroid only and 17% with a combined use of cytotoxic immunosuppressive agents. Irrespective of maintenance treatment, a majority of patients (84%) ran a fairly stable clinical course. Splenectomy was performed in 20 patients (13.2%). Roughly 10% of patients were presumed to be in the state of an apparent clinical cure.
    The preliminary results from the separately performed prospective study on 47 cases with idiopathic AIHA revealed excellent or favorable response to initial treatment with 1∼1.5 mg/kg prednisolone in 93% of patients. The hematological remission was achieved by 4 weeks in 50% and by 2 months in 83% of patients.
    Based on these data, the long-term evolution and natural history of AIHA were discussed.
シンポジウムIII 血管壁障害と凝固・線溶・血小板
  • 中村 克己
    1983 年 24 巻 9 号 p. 1214-1221
    発行日: 1983年
    公開日: 2009/01/26
    ジャーナル 認証あり
    Thromboplastic and fibrinolytic activities were estimated in layers of rabbit aortae and vena cavae, using the chromogenic peptide substrate method. Thromboplastic activities seemd to be localized, in aortae, mainly in the adventitia. The endothelium was moderately active. In aortae and the inferior vena cava, the subendothelium with the media seemed to have a higher plasminogen activator activity than other layers. These data indicate that activation of the extrinsic and fibrinolytic systems is easily induced by vascular injuries.
    Human citrated plasma was placed on the de-endothelialized surface of rabbit thoracic aorta fixed in Petri dishes and, after rotation at 4-10°C for 10 or 30 min, time dependent decline of the levels of plasma prekallikrein and of the α2-plasmin inhibitor took place, which appeared to be closely associated with contactactivation of the intrinsic system.
    Various coagulo-fibrinolytic activities were observed using the fibrin plate method in citrated plasma obtained from 40 diabetics. High levels of VIII R: Ag, VIII R: WF, VIII: C, F XII and HMW-kininogen were found in all the diabetics. The levels of the former two originating from the blood vessel were especially high in the group of diabetics with microangiopathy, who revealed an increased fibrinolytic activity, as tested after venous stasis.
    Thus, activating and inhibiting vascular factors may influence intravascular coagulofibrinolysis induced by vascular injuries.
  • 武富 嘉亮, 小金丸 茂喜
    1983 年 24 巻 9 号 p. 1222-1231
    発行日: 1983年
    公開日: 2009/01/26
    ジャーナル 認証あり
    In order to elucidate some relationships between platelets and vessel wall injury, we have studied platelet kinetics of spontaneously hypertensive rats (SHR) and also have localized the released substances of platelet granules in human intact platelets and platelets interacting with the subendothelium of rabbit aorta in vitro.
    The increased platelet production and shortened platelet survival time were observed in SHR stroke-prone (SHRSP) after 10 weeks of age. These accelerated platelet kinetics were suppressed by administration of anti-platelet drug and vitamin E. These data suggested the increased platetet consumption was brought about by vascular alteration in SHRSP.
    Using immunoperoxidase staining, we have localized the platelet factor 4, fibronectin, fibrinogen and factor VIII antigen in α-granules of human platelets. During human platelet adhesion and aggregation on the subendothelium of rabbit aorta in vitro, these released substances were localized between aggregated platelets and subendothelium as well as in adherent platelets. These antigen were also observed in vessel wall under the internal elastic lamina. During the interaction of the platelets to subendothelium of vessel wall, released substances from platelet may permeate across the internal elastic lamina of vessel wall.
  • 磯貝 行秀
    1983 年 24 巻 9 号 p. 1232-1239
    発行日: 1983年
    公開日: 2009/01/26
    ジャーナル 認証あり
    Reports expressing concern over hemorheological factors in recent studies of diabetic microangoiopathy (DmA) are on the increase. To elucidate the pathogenesis of DmA, hemorheological factors (HRF) such as whole blood and plasma viscosities, platelet adhesion and aggregation, maximum dynamic rigidity modulus of blood clot and plasma fibrinogen concentration were studied in 29 normal subjects and 149 patients with diabetes mellitus. Diabetic patients showed significant differences in all HRF when compared with those of normal subjects. Even in non-retinopathic diabetics, a third of the subjects showed significant abnormality in each of these HRF. And this paper concerns some studies that attempt to correlate intravascular erythrocyte aggregation (IEA) in eye bulbar conjunctiva with the extent of hemorheological abnormalities and the severity of retinopathy in diabetics. In the cases where a high degree of IEA were observed in vessels of the conjunctiva, there were many of advanced retinopathy or involved with blood disorders. Further we studied the fiterability of red cells in diabetics by using the negative pressure filteration system. A significant increase of HbA1 was suggested to be closely related to the decrease of red cell fiterability. These abnormalities of HRF would lead to interference with microcirculation of retinal vessels to cause local hypoxia and microangiopathy in diabetics.
  • 武田 成彰, 大里 敬一
    1983 年 24 巻 9 号 p. 1240-1249
    発行日: 1983年
    公開日: 2009/01/26
    ジャーナル 認証あり
    The role of vascular injury in the development of DIC is evaluated by the analysis of clinicopathological and experimental studies. Among the 104 cases with disseminated intravascular coagulation (DIC), there were some patients whose pathogenesis of the development of DIC was thought to be closely related to the vascular injuries. In the cases of DIC with autoimmune deseases such as SLE, HUS, TTP and Goodpasture syndrome, the impairment of vascular structures was the prominent manifestation and combined deposition of immunoglobulin, complement and fibrin on the capillary vessel wall was demonstrated.
    As for the animal model of vascular injury, acute diabetic ketoacidosis was made in rabbits by the intravenous injection of alloxan. The early stage of endothelial damages in the capillary vessels of the kidneys was demonstrated electron-microscopically and coagulation study of the animals also revealed hypercoagulability of the blood. Hypotension induced by exanguination resulted DIC only in the diabetic rabbits and not in normal control rabbits.
    Besides activation of blood coagulation and vascular injury, stasis in the microcirculation was thought to be necessary for the development of DIC. These three mechanisms known as Virchow's triad are recognized as being prime importance in the etiology of DIC like as mentioned on the causes of classical the thrombosis.
  • 山崎 博男, 田上 憲次郎
    1983 年 24 巻 9 号 p. 1250-1259
    発行日: 1983年
    公開日: 2009/01/26
    ジャーナル 認証あり
    Many of reports showed an enhancement of blood coagulability, a decrease in fibrinolytic activity and an enhancement of platelet function in arteriosclerotic diseases. However, there were several discrepancies in the above results. we have found an enhancement of platelet aggregation associated with a consumption of larger platelets which are known to have hyperfunction in arteriosclerotic patients. The circulating platelets in these patients contained less amount of ADP compared to those collected from healthy control. The plasma thromboxane B2 and 6-keto-PGF1α levels and the platelet TXA2-synthetizing activity of the arteriosclerotic patients were similar to those collected from the healthy control. In the acute stage of myocardial infarction, TXA2-synthetizing activity of platelets showed a marked decrease. The results suggest that platelets in the arteriosclerotic diseases were activated by the presense of injured surfaces of blood vessels and the activated platelets were consumed selectively in the circulation. On the one hand, platelet sensitivity to ADP aggregation, plasma von Willebrand factor and plasma β-thromboglobulin increased significantly after an isometric exercise in the arteriosclerotic patients. The changes were prevented by a pretreatment of anti-platelet drugs. The isometric exercise may induce platelet activation accompanied with release reaction in vivo through an interaction with arteriosclerotic lesions in blood vessels and may produce a thrombogenic tendency in the arteriosclerotic diseases. The changes in platelets may play an important role in atherogenesis also.
臨床研究
  • 関根 勇夫, 内海 治郎, 栗谷 典量, 東 音高, 三間屋 純一, 四家 正一郎, 小泉 晶一, 今宿 晋作, 山本 茂, 二宮 恒夫, ...
    1983 年 24 巻 9 号 p. 1260-1270
    発行日: 1983年
    公開日: 2009/01/26
    ジャーナル 認証あり
    Forty-eight immunocompromised patients receiving antileukemic drugs and/or steroid with herpes infections were treated with either intermittent (Group A) or continuous (Group B) infusions of Acyclovir (ACV), a new antiviral agent, to compare its clinical efficacy and side effects, from April to December 1982, by the Children's Cancer and Leukemia Study Group.
    The clinical effective rates were high, being 96% and 91% in Group A and B, respectively. The difference was not statistically significant.
    There were no significant difference between Group A and B in the following assessments; the time until the body temperature became normal, the time to the disappearance of vesicles, the time to scab formation and the time to the disappearance of pain following commencement of treatment.
    Viral cultures of vesicle samples taken before and at 2 days of ACV administration were positive, but at 3 days they were negative or scabs had rapidly formed. Two patients showed changes in biochemical tests, one in renal function and the other in hepatic function, which seemed to be due to their primary diseases.
    ACV treatment showed a significant impovement (p<0.05) compared with non-treatment, and there were no differences in the clinical results between intermittent (A group) and continuous (B group) infusion.
  • 山口 一成, 西村 弘道, 高月 清
    1983 年 24 巻 9 号 p. 1271-1276
    発行日: 1983年
    公開日: 2009/01/26
    ジャーナル 認証あり
    Concerning malignant lymphoma and ATL of in-patients at our hospital since 1981, hematological as well as virological investigations were done.
    1) In the non-Hodgkin lymphoma group, about half of the cases showed T-cell type, which is similar to that seen in other regions of Kyushu. Diffuse lymphoma was most prevalent, affecting about 87% of the patients, and more than 85% showed progressive status more than stage III.
    2) There were 13 cases of ATL. Conspicuous increases in serum LDH value and peripheral blood leukocytes were observed. In 7 cases, hypercalcemia was recognized. It was resistant to treatment, and the prognosis was unfavorable.
    3) The positivity rate of anti-ATLA antibodies in serum was 100% in ATL and was 50% in T cell type lymphoma, but the rate was lower in B-cell type and null-cell type lymphoma.
    4) In the detection of anti-ATLA antibodies in 13,329 healthy adults inhabiting Kumamoto Prefecture, the rate of positivity increased with aging, and was higher in females than in males. As for geographical distribution, it was higher in a certain area but was found to be widely distributed throughout the prefecture.
  • 原田 実根, 末永 孝生, 三沢 利博, 青柳 直樹, 中尾 真二, 上田 幹夫, 近藤 邦夫, 尾高 和亮, 大竹 茂樹, 手島 博文, ...
    1983 年 24 巻 9 号 p. 1277-1284
    発行日: 1983年
    公開日: 2009/01/26
    ジャーナル 認証あり
    Blood fransfusions in 22 marrow transplant patients (13 allotransplants and 9 autotransplants) were studied in regards to requirement of blood components, alloimmunization, refractoriness to platelet transfusions and cytomegalovirus infections associated with granulocyte transfusions. When blood transfusions required until engraftment were compared, allotransplant patients received more red cell and platelet transfusions than autotransplant patients. This reflects delayed hematologic recovery in allotransplant patients. Further requirement of red cell or platelet transfusions was observed in 4 patients without platelet recovery compared with those with platelet recovery. Two patients developed refractoriness to platelet transfusions. Alloimmunization was confirmed in these patients who showed positive tests for lymphocytotoxic antibodies before transplantion. No relationship was observed between granulocyte transfusions and cytomegalovirus (CMV) infection or interstitial pneumonia. These observations suggest that transfusion-related alloimmunization is not so frequent in bone marrow transplant patients and most of CMV-associated interstitial pneumonia is not related to exogenous CMV infection but reactivation of endogenous CMV.
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