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Abstract.

The case of a 34-year-old man with relapsing Ph+ acute lymphoblastic leukemia (ALL), which occurred five months after allogeneic bone marrow transplantation, is described. He was originally treated with aggressive chemotherapy, which put him in hematological remission, and he subsequently received donor leukocyte infusion (DLI) form the original donor. To assess the efficacy of this adoptive immunotherapy, we monitored minor-BCR/ABL (m-BCR/ABL) mRNA levels using the recently established real-time quantitative RT-PCR (RQ-PCR) assay. The results were compared with those obtained using conventional qualitative RT-PCR assays run in parallel. RQ-PCR, but not RT-PCR-based, minimum residual disease (MRD) detection showed a good correlation with the rapid changes documented during the post-DLI clinical course. Currently, six months after DLI, the patient continues to be in remission, which is consistent with the undetectable levels of m-BCR/ABL mRNA in the leukemic clone using RQ-PCR found in this study. Thus, monitoring of m-bcr/abl transcripts using RQ-PCR provides more useful information on a clinical assessment of MRD.

To identify the primary pathogenic factors involved in the development of Type 2 diabetes mellitus (DM), we studied Japanese women with former gestational diabetes mellitus (GDM) who are at risk for the later development of Type 2 DM. We used the minimal model analysis derived from frequently sampled intravenous glucose tolerance test (FSIGT). The subjects consisted of eight non‐obese women with a history of GDM and eight non‐obese normal women as control subjects. The 75 g oral glucose tolerance test (75 g OGTT) performed within 6 months of delivery confirmed that all the subjects with former GDM had a normal glucose tolerance. Insulin sensitivity (SI) derived from the minimal model analysis was not different between the two groups. Glucose effectiveness at zero insulin (GEZI), reflecting tissue glucose sensitivity, was significantly lower in former GDM patients than in control subjects (1.18 ± 0.34 vs 2.26 ± 0.29 × 10−2min−1, p< 0.05). The early phase insulin secretion found in FSIGT was markedly reduced to 56 % of that observed in control subjects (1250 ± 187.4 vs 2223 ± 304.3 pmol l−1min, p< 0.01). Our results indicate that in former GDM patients, who are Japanese and non‐obese, impairment of the acute insulin response to glucose and a decrease in tissue glucose sensitivity rather than insulin sensitivity are the primary pathogenic factors involved. Copyright © 1998 John Wiley & Sons, Ltd.

We conducted a multicenter trial of treatment with all-trans retinoic acid (ATRA) for newly diagnosed acute promyelocytic leukemia (APL) in the AML-92 study and compared it with our previous study with standard intensive chemotherapy, the AML-89 study, in the view of complete remission (CR) rate, incidence of early death, and event-free survival (EFS). Patients were scheduled to receive oral ATRA 45 mg/m2 daily until CR. If patients had leukocyte counts above 3 x 10(9)/L at the start of therapy, they received daunorubicine (DNR) 40 mg/m2 for 3 days and behenoyl cytosine arabinoside (BHAC) 200 mg/m2 for 5 days in addition to ATRA. During the ATRA therapy, if patients showed myeloblast plus promyelocyte counts higher than 1 x 10(9)/L in the peripheral blood, they received additional DNR and BHAC in the same schedule, as well. A total of 110 patients were entered into the study. Median age was 43 years (range, 16 to 74). Twenty-eight (26%) of 109 patients (one died before the start of therapy) received ATRA alone. Ninety-seven patients (89%) achieved CR; 48 of 49 (98%) aged less than 40 years, 44 of 52 (84%) aged between 40 and 69, and 5 of 8 (63%) aged above 70 achieved CR, respectively; 25 of 28 (89%) with ATRA alone, 46 of 51 (90%) with ATRA plus initial chemotherapy and 26 of 30 (87%) with ATRA plus later chemotherapy attained CR, respectively. Nine (8%) patients died within 28 days after the start of therapy. In contrast, 44 of 62 patients (71%) attained CR, and 13 (21%) died within 28 days in the AML-89 study with the combination of DNR, BHAC, 6-mercaptopurine and prednisolone. Seven developed retinoic acid syndrome and one died of it in the present study. Other toxicities associated with this drug included cheilitis, desquamation, muscle pain, and hypertriglyceridemia. Predicted 23 months EFS for all ATRA-treated patients and disease-free survival (DFS) in the CR cases were 75% and 81%, respectively, in a median follow-up period of 21 months. Compared to the AML-89 study, there was a highly significant difference in remission rate (P = .004), EFS (P = .0007), and also early mortality rate (P = .02). Present results demonstrated that ATRA with or without chemotherapy gives a statistical improvement in CR rate and early mortality rate, as well as superior survival in newly diagnosed APL.

Polyclonal antisera to synthetic peptides matching sequences on the cytoplasmic regions of connexin-43, a gap junction protein first identified in rat heart, have been used to immunolabel gap junctions in the calvarial bone, maintained intact as in vivo, of 1- to 2-week-old rats. The specimens were examined in reflection and fluorescence modes by scanning laser confocal microscopy, and the numbers of gap junctions and their sizes estimated. The mean number of connexin-43 immunolabelled junctions per osteoblast (n=65) was 15.3 (SD ± 4.5). The mean length of 227 junctions, selected for the sharpness of the image of the fluorescent spot, was 0.67 µm (SD ± 0.18; range 0.37–1.29 µm) and their mean area 0.26 µm2 (SD ± 0.145; range 0.075–0.93 µm2); these probably fell within the upper half of the total size range. Gap junctions were detected between preosteoblasts, osteoblasts, osteocytes and chondrocytes, and between these juxtaposed cell types. In addition, connexin-43 immuno-labelled junctions were found between some osteoclasts and overlying mononuclear cells at active sites of resorption.

We present here the unique image of toxoplasma encephalitis in a transplant recipient, characterized by the finding of T1-hypersignal foci. It is emphasized that cerebral toxoplasmosis after stem cell transplantation may show a high signal on T1-weighted images even without any hemorrhagic or calcified lesions.

Biotransformation of thujopsene (1) using a cell suspension culture of Caragana chamlagu for 14 days gave mayurone (2, 52%) and two new compounds, 3β-hydroxy-4-thujopsene (4, 16%) and 3β-epoxythujopsa-5β-ol (3, 22%).

Ozonolysis of cycloartanyl acetate (I) yields the hydroxycycloartanone (II), together with the known ketone (III).