Hideo Tokuhiro

Changes of common fragile sites on chromosomes according to the menstrual cycle

SummaryThe frequencies of chromosomal breaks and sister chromatid exchanges (SCE) are influenced by pregnancy, oral hormonal contraceptives and the menstrual cycle. The changes in the number and sites of spontaneous and aphidicolin-induced breaks on chromosomes from peripheral blood lymphocytes during the menstrual cycle were examined in 8 healthy women. Menstrual cycle was determined by menstruation and the quantity of serum estrogen, progesterone and luteinizing hormone. The number of spontaneous breaks at the follicular phase, the interval phase (which includes ovulation) and the luteal phase were 3.1 ± 1.1, 2.7 ± 2.3 and 3.9 ± 2.6 per 100 mitoses, respectively. The frequencies of aphidicolin-induced breaks in the same phases were 95.8 ± 23.3, 90.6 ± 14.3 and 122.7 ± 20.1 per 100 mitoses, respectively. The higher frequency at the luteal phase was statistically significant compared with the other phases. In the luteal phase, bands 2q32, 3q27, 6q26 and 16q23 had higher frequencies of breaks (P < 0.05); however, breaks at band 9q32 decreased significantly. SCE showed considerable variation, but with no statistical significance.

Chronic Myelocytic Leukemia: Ultrastructural Histopathology of Bone Marrow from Patients in the Chronic Phase

We investigated the ultrastructural changes in the hematopoietic microenvironment of the bone marrow obtained from 15 untreated patients with chronic myelocytic leukemia (CML) in the chronic phase by transmission and scanning electron microscopy using the cryofracture technique. Examination of the undecalcified bone marrow specimens confirmed extensive hyperplastic granulopoiesis. In the stroma, fat cells were scarce or absent. Macrophages were increased and scattered throughout the marrow. The cytoplasm contained abundant cellular debris and crystals of the Charcot-Leyden type. Slender reticular cells were inconspicuously located between proliferating myeloid cells. A few foci of fibrosis were occasionally observed. The sinus endothelium generally retained its continuity, and no features suggesting complete deterioration of the sinus were evident. However, certain alterations in the sinus wall were noted in the process of leukemia cell migration. Many cells migrated transcellularly into the circulation through transient large openings in the sinus endothelium.

Bone marrow sinus and cell egress in human leukaemia: a morphometric study of core biopsies using wide-field electron microscopy.

Bone marrow biopsy specimens obtained from 24 untreated patients with several types of acute leukaemia (AL) and eight patients with chronic myelocytic leukaemia (CML) were prepared without decalcification for electron microscopy. A new type of transmission electron microscope (LEM 2000) was used for wide‐field observation, and the venous sinuses were morphometrically evaluated on micrographs using an automatic image analyser. No differences were found between either AL or CML bone marrows and the controls in the diameter, circumference, or luminal and endothelial area of sinuses. No degenerative changes were observed in the sinus endothelium of either the AL or CML patients, but the adventitial cell cover in sinuses was significantly less in both AL (P < 0.001) and CML (P < 0.001) patients than in the controls, indicating a close relationship between the decrease in adventitial cell cover and increase in migrating leukaemia cells. In addition, the sinus endothelium in CML had significantly (P <0.03) more pores than in AL patients and three or more leukaemic cells in migration through the same large pore were occasionally found in the CML patients. These findings suggest that leukaemic cell migration in AL differs from that in CML.