Hypercalcaemia due to all-trans retinoic acid.
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Biomedical subjects
Publications and source records attributed to H Sakamaki.
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To investigate leukemogenesis of acute promyelocytic leukemia (APL), we studied the involvements of retinoic acid receptor alpha (RAR alpha) and myl genes, and also the frequency of N-RAS, K-RAS, H-RAS, and FMS point mutations in sixteen patients with APL. By Southern blot analysis, the rearrangements of RAR alpha gene were detected in 13 patients (81.2%), and myl gene in 14 (87.5%). Either RAR alpha or myl gene rearrangements were found in all patients including one with normal karyotype. Breakpoints of both genes were clustered. By direct sequencing, no point mutations were found at codons 12, 13, and 61 of N-, K-, and H-RAS genes, and at codons 301 and 969 of FMS gene. These data indicate that myl-RAR alpha translocation occurs frequently in APL, whereas RAS and FMS mutations are rare in APL. It may be suggested that leukemogenesis of APL is different from other subtypes of acute myelogenous leukemia, and multistep leukemogenesis may not be a prevalent feature in APL.
This retrospective study examines the effects of treatment modalities and other contributing factors on the duration of trismus following mandibular fractures. Under a strict protocol, 80 cases involving a total of 120 fractures and their treatment modalities were reviewed. An investigation of duration of trismus was carried out in several ways. Although a relationship was established between age, initial interincisal distance, and duration of trismus, no relationship was found with the number or location of fractures, or reduction method. However, after examining the fixation methods separately, it was found that those cases in which Champy plates were used experienced a shorter duration of trismus compared with those using closed reduction with maxillomandibular fixation.
A 54-year-old woman developed transfusion-associated graft-versus-host disease (TA-GVHD) after the transfusion of stored packed red cells obtained from unrelated donors. The patient was presumed to be immunocompetent. A diagnosis of TA-GVHD was made by clinical features and postmortem pathologic findings. Sex chromatin analysis of the patient's lymphocytes demonstrated chimerism. HLA typing of the blood donors revealed one to be HLA-homozygous for one of the patient's HLA haplotypes (A33-B44-Cblank). This case illustrates the risk in the general patient population of TA-GVHD after routine blood transfusion therapy. Workers should be aware of this possibility and should continue searching for an efficient way to prevent it.
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A 22-year-old man with T cell type acute lymphoblastic leukemia in first remission underwent autologous bone marrow transplantation (BMT). The preparative regimen included cytosine arabinoside, cyclophosphamide and fractionated total body irradiation. His harvested bone marrow cells were purged with 4-hydroperoxycyclophosphamide. His serological test was positive for cytomegalovirus (CMV) before the BMT. On day 53 after the BMT, he developed dry cough and his chest X-ray film showed bilateral basilar infiltration. Bronchoalveolar lavage was performed and cytology of the specimen revealed typical cytomegaloviral inclusion bodies. DNA analysis and viral culture of the specimen were also positive for CMV. The patient was started on ganciclovir and immunoglobulin with high dose methylprednisolone. His respiratory status deteriorated, however, and the patient expired because of respiratory failure. Autopsy revealed severe interstitial pneumonitis with suppression of CMV replication from the treatment. Interstitial pneumonitis due to CMV should be considered as a significant complication of autologous BMT.
Between 1983-1988 bone marrow samples obtained from 195 peroxidase-negative leukemia patients were analyzed for their surface antigens. Thirteen of these patients (6.7%) had myelomonocytic-positive and lymphoid-negative antigens. These leukemic cells reacted with CD13 in eight patients, CD33 in seven, CD11 in six and CDw41 in two. In none of these patients did the leukemic cells react with CD1, CD2, CD3, CD4, CD5, CD8, CD10, CD19 or CD20. Leukemic cells from two patients were reactive with CD7. These leukemic cells demonstrated L2 morphology in 11 patients and L1 morphology in one patient. The leukemic cells from the final patient were diagnosed as those of leukemic transformation of myelodysplastic syndrome. Chromosomal abnormality was observed in approximately half of the patients examined (6/10). Cytochemical analysis revealed that the leukemic cells were negative for periodic acid Schiff stain but positive for acid phosphatase. The prognosis of these patients was markedly poor as compared to acute lymphocytic leukemia or typical peroxidase-positive nonlymphocytic leukemia. Complete remission was induced in only 30% of patients and duration of survival was short (4.7 months). This suggests that myelomonocytic antigen-positive peroxidase-negative acute leukemia is a distinct type of leukemia and may require more aggressive therapy to improve survival.
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Two cases of granulocytic sarcoma of the ovary found at the time of relapse of acute myelogenous leukemia (AML) are presented. Almost 5 years after the initial diagnosis of AML, both cases presented ovarian tumors which were discovered to be myeloblastoma of the ovary on laparotomy in one case and at the time of autopsy in the other. Evidence of hematological relapse followed the presentation of the ovarian tumor within a month. Both patients were treated with surgery and/or chemotherapy.
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Disseminated atypical mycobacterial infection has been reported mainly in patients with AIDS and hairy cell leukemia. We describe three patients with chronic myelogenous leukemia (CML) who developed disseminated atypical mycobacterial infection in the chronic stage of their disease. The incidence of the latter infection is 3.9% among patients with CML at our institution; such a high incidence has never before been reported. There are no specific signs or symptoms other than fever. The bone marrow is the culture site most often useful in diagnosis. An immunologic defect may be one of the features of CML. Clinicians must thus be aware of the possibility of disseminated atypical mycobacterial infection in patients with CML.