Nihon Ketsueki Gakkai zasshi : journal of Japan Haematological Society最新文献

The clinical usefulness of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) levels in serum and pathogenetic mechanism of hypoalbuminemia and hypocholesterolemia in multiple myeloma (MM) were investigated. In cases of MM with a history of pathological fracture, the level of serum ALP was significantly higher than normal. Thus, elevated ALP in MM patients may be an indicator of the occurrence of a pathological fracture within the past 2 months. The levels of serum LDH in about 80% of the MM patients were within normal limits despite the presence of a malignant tumor. These patients showed a normal pattern of isoenzymes and more mature types according to the Greipp classification. In contrasts, the patients with elevated serum levels of LDH showed the tumor pattern of the isoenzymes and the plasmablastic type. The total cholesterol concentration was correlated with the total protein levels and the serum cholinesterase. These findings were the same as those in patients with nephrotic syndrome and polyclonal hypergammaglobulinemia without liver dysfunction. These results suggest that the decreased cholesterol in MM is due to a reduction in the synthesis of albumin in the liver.

A survey on the survival of a total of 160 patients with paroxysmal nocturnal hemoglobinuria (PNH) was conducted by questionnaires to hematologists at the 86 major hospitals in Japan. Ten, 20 and 30 year-survival rates from the day of diagnosis was 71%, 57.5% and 57.5%, respectively. The survival curves by sex showed no statistical difference between males and females. The cause of death in 56 patients with PNH was investigated. Twenty cases, representing 38.5% of 52 patients excluding 4 cases of unknown cause, died of hemorrhage. Death from thrombosis occurred only in 3 cases. The incidence of hemorrhage and thrombosis as a cause of death in Japanese patients was clearly different from that in the United States and England. Various causes other than hemorrhage and thrombosis were disclosed. Patients died 4.5 years (median) from diagnosis and at a mean age of 50.4 years. Hypoplastic bone marrow was found histologically in 40.4% of 52 patients by biopsy. The findings of peripheral blood and aspirated bone marrow were nearly consistent with those of hypoplasia. A higher incidence of hemorrhagic death in Japanese patients might be related to thrombocytopenia by hypoplastic bone marrow. On initial diagnosis, 41.2% had aplastic anemia-PNH syndrome. Prevention against complications in PNH with special reference to blood transfusions are discussed.

The characteristics of leukemia in elderly patients, especially acute nonlymphocytic leukemia, and therapy are reviewed. The features differ little from those in young ANLL patients, except for the frequencies of the preleukemic state and poor performance status. Preleukemic states are observed in about 30% of elderly patients and about 40% of the elderly patients have a poor performance status on admission. Anthracycline and Ara-C are generally used for the treatment of ANLL in elderly patients. Many reports suggest identifying a group of patients with favourable prognostic factors and treating them intensively. However, the prognostic factors reported were variable. A good performance status and normal- or hypocellular bone marrow were the most important prognostic factors in our study. Low dose Ara-C may be effective in ANLL in elderly patients with hypoplastic bone marrows. Supportive care is also very important in elderly patients.

Thrombocytosis occurs as a primary disease of the bone marrow (primary thrombocytosis or thrombocythemia) or as a reactive phenomenon in pathologic and physiologic conditions (secondary thrombocytosis or thrombocytosis in a narrow sense). As a rule, secondary thrombocytosis is symptomless and shows normal platelet functions, while thrombocythemia is frequently associated with bleeding and/or thrombosis as well as various platelet abnormalities. These platelet abnormalities were reviewed, and our recent studies on functional and biochemical alterations in platelets of thrombocythemia were focused on: 1) abnormal platelet aggregation. 2) deficient epinephrine-induced elevation of the cytoplasmic Ca2+ concentration in platelets with defective aggregation response to epinephrine, 3) altered (subnormal and increased) platelet responses to thromboxane A2 (abnormal thromboxane A2 receptor), and 4) abnormal platelet 12-lipoxygenase enzyme. Although the clinical significance of the in vitro qualitative platelet defects is not always clear, these altered platelets could be useful models to elucidate platelet pathophysiology.

Lymph node swelling, which can be problematic when attempting differential diagnosis between non-neoplastic or neoplastic types, can be grouped into three categories. The first is lymph node swelling due to heterotopia, hamartoma or hyperplasia, the second is due to non-neoplastic lymphoid cell and/or histiocyte proliferation with the appearance of neoplastic proliferation and the third is due to true neoplastic proliferation, but apparently simulating a non-neoplastic condition. The present paper describes some of the clinicopathological features of representative diseases or cases in each category, e.g. Castleman's disease, necrotizing lymphadenitis, "IBL"-like T-cell lymphoma, and lymphoma showing an unusual course initially simulating a non-neoplastic process and then gradually disclosing its neoplastic nature in the late stage. These cases emphasize the importance of close collaboration between the clinician and pathologist together with immunohistochemical studies of lymph node pathology.

In the first familial case of gray platelet syndrome (GPS) reported in Japan in which the subjects showed platelet release abnormalities, we investigated the relationship between intracellular Ca++ mobilization in platelets and marked morphological abnormalities of the DTS. The subjects for the Aequorin assay were 12 controls and 11 GPS cases, whereas the subjects for the Fura-2 assay were 10 controls and 6 GPS cases. In order to discriminate between Ca++ influx from outside of the cells and Ca++ mobilization from DTS within the cells, the experiments were conducted under two conditions; one in the presence of 1 mM Ca++ in the external fluid, and the other with the addition of 2 mM EDTA as a Ca++ chelator. Stimulation by A-23187 in the presence of 1 mM Ca++ in the external fluid caused 2 peaks or shoulder formation; that is, normal cases showed 1 peak at all concentrations of A-23187 tested, whereas GPS showed 2 peaks or shoulder formation in 7 of the 11 cases and conspicuously good reproducibility in each case. These facts indicated that it took time for the stimulus to reach the inside of the DTS, which showed marked morphological abnormalities. During stimulation by 1.0 U/ml thrombin under the same conditions, the GPS exhibited 1 peak with a wide skirt pattern, compared with the control. In one case of GPS, which revealed one peak by thrombin and 2 peaks by A-23187 in the presence of 1 mM Ca++, 2 peaks were also noted by thrombin and the luminescence peak become lower, when Ca++ was chelated by EGTA, using the Aequorin method.(ABSTRACT TRUNCATED AT 250 WORDS)

Agonist-induced platelet cytoplasmic Ca2+ concentrations ([Ca2+]i) in patients with congenital cyclo-oxygenase deficiency (A) and with impaired aggregation to A23187 (B) were measured with aequorin in the presence or absence of extracellular Ca2+. The influence of TMB-8 or ONO3708 on agonist-induced [Ca2+]i in those platelets was also investigated. In Patient 1, there was a single aequorin luminescence peak in response to arachidonate, which was a thromboxane A2(TXA2) independent Ca2+ influx. The luminescence peak due to the formation of TXA2 was not detectable. The A23187-induced [Ca2+] i was decreased in the presence of extracellular Ca2+, but was within normal limits in the absence of extracellular Ca2+. A thrombin or STA2-induced elevation of [Ca2+] i was always within normal limits under any conditions. These results suggest that cyclo-oxygenase activity (CO activity) contributes to the A23187-induced Ca2+ influx, but does not contribute to the Ca2+ release from intracellular stores, and that the thrombin or STA2-induced Ca2+ influx and release do not depend on the CO activity. In Patient 2, the time lag from the addition of A23187 to the aequorin luminescence peak was found both in the presence and absence of extracellular Ca2+, which was more obvious in the latter. This A23187-induced elevation of [Ca2+] i disappeared after treatment of the platelets with TMB-8 in the absence of extracellular Ca2+, which is rarely seen in normal platelets. The most striking finding was that the thrombin-induced rise in [Ca2+] i in the absence of extracellular Ca2+ was not detectable. These findings might be closely related to abnormal platelet function in this patient.

The role of urokinase-type plasminogen activator (u-PA) in capillary growth was investigated using cultured bovine endothelial cells (BCE) on type I collagen gels and analyzed by morphometry for quantitative assessment of angiogenesis in vitro. BCE migrated into the gel matrix and formed capillary-like networks. The morphometrical analyses by measuring the length of tube formation enabled us to evaluate the effects of fibrinolytic proteases and several reagents. The addition of plasminogen up to 25 micrograms/ml to the gels significantly increased the extent of tube formation of BCE in a dose-dependent manner. Basic fibroblast growth factor (10 ng/ml) increased tube formation only in the presence of plasminogen. These enhancing effects on angiogenesis appeared to be related to the activation of fibrinolysis by u-PA derived from BCE, because they were suppressed by the addition of anti-u-PA IgG and anti-plasmin reagents such as aprotinin and alpha 2 anti-plasmin. Transforming growth factor beta also enhanced tube formation of BCE, but tumor necrosis factor alpha and interleukin-1 suppressed the tube formation. The quantitative assay of angiogenesis may be useful for clarifying the mechanism of neovascularization under pathological conditions.

We evaluated the long-term prognosis and quality of cure of idiopathic acquired aplastic anemia in children. Of the 244 patients registered from 1965 to 1985, those registered in 1965-1975 and 1976-1985 had a survival rate of 50.1% and 62.0%. The percentage of cure, undertreatment and death was 30, 30 and 40%, respectively. About 40% of the patients with moderate cases, died dead or required frequent blood transfusions. In the case of pediatric patients, as the success rate of bone marrow transplantation was high. This modality should be considered for patients with moderate severity who require blood transfusion 3 months after the diagnosis and an HLA identical donor is available. Physical development was almost normal but 35% of the patients showed residual abnormalities such as bleeding tendency, and hepatic disorders due to treatment. Thrombocytopenia and ineffective hematopoiesis were observed in one-third of the patients and all of the patients showed abnormal committed stem cell assay. The CD 4/8 ratio was reduced in 50% of the patients and 15% exhibited psychological problems. These residual abnormalities last for years, and sometimes a lifetime.

Several aspects of prognosis of myelodysplastic syndromes were reviewed with special attention to refractory anemia (RA). The median survivals were 14 months in chronic myelomonocytic leukemia, 16 months in RAEB, 42 months in RA, and 58 months in RA with ring sideroblasts (RARS). Cumulative leukemia-free rates at 5 years were 31% in RAEB, 80% in RA, and 92% in RARS. The proportion of cases having very low hazards for leukemic transformation or for nonleukemic death was 92% (RARS), 73% (RA), and 26% (RAEB) for leukemic transformation and 23% (RA) and 29% (RAEB) for nonleukemic death. All RARS cases had hazard for nonleukemic death. In RA, the annual mortality rate was about 5 to 11 times higher than that of age-and sex- matched general population up to 6 years. After which no failure was found in RA cases with survival rate of 33% up to 14 years. The relative importance of hazard from leukemic transformation to nonleukemic death in RA was about one half at presentation, but this declined to less than 10% after 10 years.