Morihisa Yamagishi

The effect of low dose Ara-C in acute non-lymphoblastic leukaemias and atypical leukaemia

Nine patients with nonlymphocytic leukaemia and one patient with refractory anaemia with excess of blasts (RAEB) were treated subcutaneously with Ara‐C at a low dose of 10 mg/m2/12 h; complete remission was obtained in seven patients. In all cases severe pancytopenia was observed during treatment. We measured the concentration of Ara‐C in serum, and found that the maximum concentration reached a peak (52‐132 ng/ml; mean 84‐2 ng/ml) at 15 min following injection. These concentrations can be considered sufficient to inhibit DNA synthesis. Primary short‐term culture of human leukaemic cells with low dose Ara‐C was also performed, and differentiation of leukaemic cells was observed for several types of leukaemic cells. The in vitro findings corresponded to the observed clinical effects. From the above results, the action of low dose Ara‐C may have resulted from a combination of two different mechanisms, its cytostatic effect and its differentiation‐inducing effect.

MDS‐macrophage derived inhibitory activity on myelopoiesis of MDS abnormal clones

Summary. We studied the effect of myelodysplastic syndrome (MDS)‐derived adherent cells on colony formation of granulocyte‐macrophage progenitors (CFU‐GM) in both normal and MDS bone marrow cells. MDS‐adherent cells suppressed the growth of normal CFU‐GM colony formation. Antibodies against ferritin almost totally neutralized the haematopoietic inhibitory activity. Antibody against gamma‐interferon (γ‐IFN) did not have such effect.

Radioautographic studies on the formation and maturation of bone marrow lymphocytes in mice

Abstract. DNA labelling by [3H]thymidine and the sandwich radioimmunolabelling method were used to characterize marrow lymphoid cells and to study the kinetics of production and maturation of small lymphocytes in the bone marrow of adult mice. Marrow lymphoid cells consisted of non‐proliferating small lymphocytes, 30–40% of which had detectable surface immunoglobulin (SmIg), and proliferating large lymphoid cells lacking SmIg. Double‐labelling experiments employing [3H]thymidine in vivo followed by sandwich radioimmunolabelling in vitro indicated that marrow small lymophocytes lack detectable SmIg when they are formed but develop SmIg within the first few days after production. Marrow lymphocytopoiesis includes; (1) praliferation of large lymphoid cells, which are presumptive small lymphocyte progenitors, which have a cell cycle time of 14–15 hr, and (2) a 3–5‐day intramyeloid stage when many newly formed small lymphocytes undergo maturational changes towards the B cell lineage.

Laboratory diagnosis of anemia and related diseases using multivariate analysis

To establish a simple computer program for the laboratory diagnosis of anemia and related diseases, multivariate analyses were applied to the results of routine hematological laboratory tests obtained from 48 patients and 51 healthy volunteers. The patients studied were limited to those who had not been treated hematologically by the time of their first visit to our hospital, and their first data obtained in our laboratory were analyzed. Final diagnoses were aplastic anemia (AA) in 21, myelodysplastic syndrome (MDS) in 14, iron deficiency anemia (IDA) in 3, polycytemia vera (PV)in 3, and idiopathic thrombocytopenic purpura (ITP) in 7. Eight parameters, WBC, RBC, Hb, Ht, MCV, MCH, MCHC, and PLT, were transformed to normal distribution and then applied to principal component analysis to evaluate their independence. Very close relationships were observed between Ht and Hb, and between MCV and MCH. One each of these pairs was selected by discriminant analysis and two sets, RBC, MCH, Hb, PLT, and WBC, and RBC, MCV, Ht, PLT, and WBC, were obtained. Two canonical components gave good discrimination of these five diseases and also of normal subjects. When disease prediction was made using this analysis, 37 of 48 patients (77.1%) were predicted correctly, and furthermore, when two disease predictions were allowed, all patients were diagnosed properly. Some overlaps were observed in this two‐dimensional coordinate system, especially of AA and MDS, and also with normal subjects. To improve the system further, the additional parameters of age and sex were added to construct a three‐dimensional analysis which resulted in much clearer discrimination. The whole procedure described is being developed with subjects who are not taking medication. Subsequently, the general application of this analytical procedure should be limited to only those not on medications. In conclusion, this is in essence a demonstration project; however, this trial of laboratory diagnosis using routine hematological laboratory results appears to be promising. Further extension of the study by increasing numbers of patients and disorders studied, including secondary anemias, will allow the design of diagnostic software for use with personal computers at the sites of primary care. Am. J. Hematol. 54:108–117, 1997

PRIMARY THROMBOCYTHEMIA ASSOCIATED WITH ERYTHROMELALGIA, WITH A SPECIAL REFERENCE TO THE MECHANISM OF PAIN: REPORT OF A CASE

原発性血小板血症といわれるものには,いわゆる“thrombohemorrhagic phenomena”を呈するものと血栓形成又はそれに近似する症状を呈する場合のものとが臨床的に報告されている.血小板増加の原因はもちろん,出血や血栓形成,疼痛などの発現機序についてはほとんど解明されていないのが実情である.最近著者等は78才,女性で典型的erythromelalgiaを伴つて発症し,何ら基礎的疾患と思われるものなく,持続する血小板増加と趾疼痛を来たした原発性血小板血症の1例を経験した.検査上,末梢血中血小板は100×104/μI以上の増加を認めるが,その他の成績に著変なく凝固,線溶系の検査もほぼ正常であつた.また骨髄塗抹,生検所見では従来本症に特徴的と言われる巨核球系を中心とした過形成がなく,この点からも自験例は希な症例と言える.しかも趾疼痛がaspirin l回の投与により7～10日間は完全に消失した事実から疼痛の発現と血小板機能との関係に検討を加えた.すなわちaspirinは血小板機能発現に重要なprostaglandin (PG) endoperoxidesの生成酵素であるcyclooxygenaseを非可逆的に阻害し血小板凝集阻止を行なう事から, PG eodoperoxidesに由来すると考えられるmalondialdehyde (MDA)を指標としてaspirin投与後のPG endoperoxides生成や,血小板凝集能を検索したところ,疼痛発現にはこれらの血小板機能が密接に関与している事が明らかとなつた.また治療では欧米で盛んに用いられて来た32Pは使用せず, busulfanpによる化学療法を試みた結果,血小板数の減少とともに疼痛も消失し満足すべき治療効果が認められた.