Chromosome rearrangement, t(6;14) (p21.1;q32.3), in multiple myeloma.
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Biomedical subjects
Publications and source records attributed to S Misawa.
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Using a human myeloperoxidase cDNA, we have mapped the human myeloperoxidase gene to chromosome 17 at q21.3----q23 by in situ hybridization to metaphase chromosomes from human lymphocyte preparations.
Nonspecific cross-reacting antigen (NCA) is a member of the carcinoembryonic antigen (CEA) gene family. Recently, a DNA segment for part of the human NCA gene was isolated and sequenced. We mapped this gene by Southern blot analysis of hybrid cells and by in situ hybridization. The Southern blot analysis indicated that the NCA gene is on human chromosome 19 and the in situ hybridizations localized the gene to band 19q13.2.
A 44-year-old Japanese male having refractory anemia with excess of blasts (RAEB) preceding acute myelomonocytic leukemia (AMMoL) with dysplastic marrow eosinophilia (M4Eo in the FAB classification) is reported. Sequential cytogenetic studies revealed a specific chromosomal abnormality, inv(16) (p13q22), when RAEB was first diagnosed and again when overt leukemic transformation compatible with M4Eo was manifested. However, during the interval between the RAEB and AMMoL, an unrelated abnormal karyotype without inv(16), 47,XY,+9, was seen, when hematological data revealed remission after a low dose of cytosine arabinoside was administered. In this patient eosinophils in the marrow were involved in the leukemic process cytogenetically, because a few metaphases overlaid with eosinophilic granules had the inv(16) with other numerical abnormalities.
The metabolism and excretion of trimethadione (TMO) following an oral dose of 4 mg/kg has been examined in patients with percutaneous transhepatic biliary drainage (PTBD) and renal dysfunction. Biliary excretion as the total amount of TMO and its metabolite, dimethadione (DMO) was 2.0% of the dose during 0 to 48 h after TMO administration in patients with PTBD. Total urinary excretion (0-48 h) was 2.8% and 3.0% of the dose in healthy volunteers and patients with renal dysfunction, respectively. The serum DMO/TMO ratio at 4 h after oral dosing in patients of PTBD and renal dysfunction was not significantly changed in comparison with the ratio reported previously in healthy volunteers. The elimination half-life of TMO was also not altered in patients with PTBD in comparison with that reported previously in volunteers. These results suggest that metabolism and urinary and biliary excretion of TMO are not changed in patients with PTBD and renal dysfunction.
Mitochondrial DNA restriction fragment length polymorphisms (mtDNA RFLPs) were surveyed among 19 Japanese families with 67 individuals including twins. A mother and children, and siblings of each family showed the same pattern of mtDNA RFLPs. Samples from Japanese war orphans remained in China and their probable relatives were also surveyed and one pair indicating a high probability to be siblings using other genetic markers possessed the same variant of mtDNA. Moreover mtDNA RFLPs was applied for maternity test among two families. The data suggested that parents mistook their children for each other at birth.
Six patients with chronic myelogenous leukemia and a complex Philadelphia (Ph1) translocation are described. The complex Ph1 translocations were a three-way translocation in five patients and a five-way translocation in one. Additional chromosomal aberrations were detected in four of five patients when the blastic crisis supervened. The median survival time was 42 months. The remaining patient died of acute myocardial infarction 23.5 months after the diagnosis of CML was made. There seems no difference between these six patients and those with the standard Ph1 with respect to clinical, hematologic and cytogenetic findings.
The efficacy and the safety of a combination regimen using cefbuperazone (CBPZ) and amikacin (AMK) were evaluated in severe infections in patients with hematological diseases. Twenty two patients were subjected to this combination therapy; among these, 18 patients were evaluable for the effectiveness. They included 9 cases of leukemia, 5 cases of malignant lymphoma, 2 cases of aplastic anemia, and 2 cases of angio-immunoblastic lymphadenopathy with dysproteinemia. Excellent responses were obtained in 5 patients and good responses in 5 patients, with a total effectiveness of 55.6%. Efficacy rates for individual types of infections were; 2/2 in sepsis, 6/14, or 42.9% in suspected sepsis, 1/1 in urinary tract infection, and and 1/1 in upper respiratory infection. The combination treatment was also effective in 4 of 6 cases in which neutrophil counts were less than 500/mm3 prior to therapy. Side effects were observed in only one patient. Mild proteinuria occurred in a 80-year-old male in 6 days after the regimen was started, but was not serious. These results indicate that a combination of CBPZ and AMK is safe and effective for the treatment of infections even in patients with compromised immunodefenses.
In 1982, the French-American-British (FAB) Cooperative Group proposed the myelodysplastic syndrome (MDS), which comprised a group of heterogeneous hematologic disorders characterized by various degrees of cytopenias and a possibility of leukemic transformation. And chromosome findings of bone marrow cells from patients with this syndrome are reported to have one of the greatest prognostic significance. In our chromosome study of 97 patients with MDS, we found clonally abnormal karyotypes in 61 patients (63%), including the whole chromosome or partial loss of long arm of chromosome 7 (-7/7q-) in 18 patients and a partial loss of chromosome 5 (5q-) in 14 patients. Among these 97 patients, 26 received cytostatic chemotherapy (small dose of cytarabine; 23 patients, small dose of behenoyl Ara-C; 2, and intensive combined chemotherapy; 1) as well as supportive care. Among these 26 treated cases, pretreatment hematological characteristics or FAB subclassifications were not associated with response to chemotherapy. In contrast, only one of 9 patients with -7/7q- and/or 5q- achieved a partial remission, while 5 of 8 patients with other abnormal karyotypes and 4 of 9 patients with normal karyotype achieved a complete (4 patients) or a partial remission. In conclusion, pretreatment cytogenetic findings can predict the potential responders to this chemotherapy, and may be one of the most important factors in the selection of the treatment for this ill-managed syndrome.
Forty one patients with infections associated with leukemia and related disorders were treated with cefpiramide (CPM). In 26 patients among them, we were able to evaluate the effectiveness of CPM against infections. Fifteen patients were not evaluated, because 6 patients were subjected to additional therapy such as gamma-globulin and other antibiotics, 5 were prophylactically treated, 2 had fever episode which were retrospectively reviewed to be originated from tumor mass, 1 received too short a duration of administration of CPM (2 days) to evaluate its effectiveness, and 1 with whom no precise data were recorded. Excellent responses were observed in 10 patients (38.5%) and good responses in 6 (23.1%) among these 26, with a total efficacy rate of 61.5%. Whereas, we found only one patient who showed an unfavorable side effect out of 31 patients including the 26 and 5 other patients who were prophylactically treated. The side effect observed was a mild bleeding tendency occurred in 77 years old female at 11 days after CPM was administrated. The bleeding tendency was easily diminished with the cessation of CPM treatment and a parenteral use of vitamin K. These results suggest that CPM is an effective and safe antibiotic for the treatment of infections in patients with leukemia and related disorders.
A combination of aztreonam (AZT) and clindamycin (CLDM) was evaluated for severe infections associated with leukemia and related disorders. AZT is a monobactam antibiotic which has strong bactericidal effect against Gram-negative bacteria including Pseudomonas aeruginosa. CLDM which has strong antibacterial spectrum against Gram-positive and anaerobic bacteria, was chosen as a partner of AZT in order to complement the weak points of AZT. Fifty six patients were treated with the combination therapy. Among them, 51 patients were evaluable for the effectiveness. Five patients were excluded from the evaluation because 3 patients were subjected to additional therapy with other agents such as amikacin, miconazole and pulse therapy of a large dose of methylprednisolone, one had a fever episode apparently due to primary disease, and the remaining one was discontinued of the combination therapy of administration due to mild nausea after 3 days. Excellent responses were obtained in 17 (33.3%) patients and good responses in 20 (39.2%) patients, with a total rate of effectiveness of 72.5%. One patient with whom the combination therapy was stopped due to nausea, was included in the final evaluation of side effects. Side effects were observed in 2 patients of 50 and 40 years of ages (2/52, 3.8%), both of whom suffered with nausea. In the 50 years patient of acute myeloblastic leukemia, nausea occurred in a slight degree in 3 hours after the combined regimen was started. But, it disappeared during the continuation of the combination therapy. In the 40 years patient of acute myelomonocytic leukemia, mild nausea occurred after 3 day administration of the combined regimen. It disappeared soon after the cessation of the treatment. These results indicated that a combination of AZT and CLDM was an effective and safe regimen for the treatment of severe infections in patients with hematological disorders.
Automotive lubricants were analysed by isotachophoresis for the purpose of identification of lubricants and suspected stains adhered to victims in traffic accidents. As the results, it was found that each lubricant showed a characteristic isotachophreogram even if they were manufactured by the same maker, and that the isotachopherogram of the lubricant changed in proportion to the running distance of an automobile. Each lubricant had its own changing rate. Moreover, A, B, C heavy oils, asphalt, soy sauce and sauce, which apparently resembled lubricants when they adhered to victims, were analysed with this method. They were found to be clearly different from lubricants in isotachopherogram and they could be discriminated from lubricants. Therefore, it was found that lubricants could be easily identified or discriminated from other lubricants such as engine oils, gear oils and other oils by comparing their isotachopherograms obtained with this method in a short time. It was, however, difficult to suggest the maker of a lubricant from isotachopherogram. We conclude from these observations that isotachophoresis method is useful for the analysis of lubricants in case of traffic accidents.
To estimate postmortem interval (PMI), spontaneous cleavage of the third component of complement (C3) was studied in aged blood and cadaveric blood by crossed immunoelectrophoresis. Using the kinetics of C3 cleavage in vitro described as dC/dt = -kC, where C is the concentration of native C3 at time t and k is a first-order rate constant, Arrhenius' equation, and another equation which assumes a linear drop of body temperature after death, the percentages of C3 cleavage were calculated. There was a significant positive correlation between the calculated percentages and the measured percentages of up to 10% in cadaveric blood. We found that the comparison between the calculated percentage of C3 cleavage for each optional postmortem interval and the measured percentage of up to 10% in cadaveric blood leads to the estimation of PMI. This approach is one step towards the development of an accurate method for determining PMI based on C3 cleavage, that is, on a first-order reaction.
In a chromosome study of 83 patients with myelodysplastic syndrome (MDS), 50 showed a clonally abnormal karyotype. The most frequent abnormalities were the whole or a partial loss of the long arm of chromosome 7 (-7 or 7q-) (14 patients) and a partial loss of the long arm of chromosome 5 (5q-) (11 patients). Twenty patients with 5q- and/or -7 or 7q- had a shorter survival (median, 5 months) than those with other abnormal karyotypes (22 months) or those with a normal karyotype (28 months). In this series 30 patients were examined cytogenetically on two or more occasions during the course of their illness. Ten patients showed a further karyotypic alteration from the initial findings, and, concomitantly, their disease progressed in severity including overt leukemia. These patients had a shorter survival (median, 2 months) after the chromosome reanalysis than the other 20 patients who did not have further karyotypic changes (21 months). Thus, the prognosis of patients with MDS can be predicted more accurately by reanalyzing the chromosomes after the initial analysis.
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A modified short-term culture method, in which cultured bone marrow cells were treated with ethidium bromide to prevent chromosome condensation was used to study the chromosomes of 70 patients with acute nonlymphocytic leukemia. Clonal karyotypic abnormalities were detected in 60 patients. Among these, 35 patients showed one of recurrent type specific alterations. A close relationship between karyotypes and clinical outcome was shown: thus, t(8;21) or a single miscellaneous chromosomal defect associated with a favourable prognosis whereas t(9;11) or a complex karyotype related to a poor prognosis. The ten cytogenetically normal patients did not appear to have a favourable prognosis.
We have studied in-vitro growth of leukemic progenitor cells (L-CFU) in ten patients with acute promyelocytic leukemia (APL). All patients showed consistently an extraordinarily high incidence of cluster formation under the stimulation of human placental conditioned medium (HPCM) and/or phytohemagglutinin-stimulated leukocyte conditioned medium (PHA-LCM). Cytogenetic analyses of clusters or colonies disclosed the presence of a 15;17 translocation. These findings may represent the close relationship between specific chromosomal aberration, t(15;17), and the growth pattern of L-CFU of APL in vitro.