Granulocyte-colony stimulating factor corrects granulocytopenia in Felty's syndrome.
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Aged↗
Biomedical subjects
K Dan
Publications and source records attributed to K Dan.
Relationship of the type of bcr-abl hybrid mRNA to clinical course and transforming activity in Philadelphia-positive chronic myelogenous leukemia.
We studied the type of bcr-abl mRNA for 34 patients with chronic myelogenous leukemia and analyzed for correlations among the mRNA type, the clinical outcome and the transforming activity using the tumorigenicity assay. There was no difference in the distribution of the mRNA-types (b2-a2 and b3-a2) between clinical phases. We found no correlation between the two types of bcr-abl mRNA and the chronic phase duration or survival. The DNA from 12 of 20 chronic phase patients and all five blastic phase patients showed transforming activity. Although there was no difference in the positive rate of transforming activity among the two mRNA-type groups, the blastic phase patients showed a tendency to have higher transforming activity.
3T3 Cells↗
Low-dose etoposide: a potential therapy for myelodysplastic syndromes.
Four patients with refractory anaemia with excess blasts in transformation (RAEB-t) and seven patients with acute leukaemia (AL) transformed from myelodysplastic syndromes (MDS) were treated with etoposide (50 mg, 2 h infusion, two to seven times per week) for at least 4 weeks. Of 10 assessable patients, three RAEB-t patients achieved partial response and one AL patient achieved complete remission. Three of the four responders were resistant to prior repeated low-dose cytarabine therapy. The responders did not require transfusions for 2-9 months while continuing on etoposide therapy. The side-effects were mild and well tolerated. Three possible mechanisms, i.e. a cytotoxic effect, differentiation-induction of malignant cells, and prolongation of blood cell survival by destroying the reticuloendothelial system, may explain the effects of etoposide. We conclude that low-dose etoposide is a potential therapy for MDS and atypical leukaemia.
Acute Disease↗
[Plasma beta-glucan levels in deep fungal infections accompanying hematological diseases and clinical efficacy of miconazole--a multi-institutional study].
Miconazole (400-1200 mg/day) was administered to patients with deep mycosis and suspected deep mycosis, and the efficacy evaluated. beta-Glucan was determined as the early diagnostic parameter of deep mycosis, and the relationships between the clinical efficacy of miconazole and the titers of beta-glucan were also evaluated. Forty-nine cases were evaluated, including 2 cases of deep mycosis and 47 cases of suspected deep mycosis. Most of the patients had hematological malignancies. The rate of efficacy was 100% (2/2) in deep mycosis, 66.0% (31/47) in suspected deep mycosis, and 67.3% (33/49) in total. beta-Glucan was determined in 39 cases before the administration of miconazole. The rate of beta-glucan positivity was 100% (1/1) in deep mycosis and 44.7% (17/38) in suspected deep mycosis. beta-Glucan was also determined before and after the administration of miconazole in 11 cases. The titers of beta-glucan became negative in 6 cases, decreased in 2 cases and increased in 3 cases. Thus, the beta-glucan titers became negative or decreased in 72.7% (8/11) of the cases. Efficacy of miconazole was 83.3% (5/6) in the cases in which beta-glucan became negative, 50.0% (1/2) in the cases in which the titers of beta-glucan decreased, and 33.3% (1/3) in the cases in which the titers of beta-glucan increased. Miconazole was effective in the treatment of deep mycosis, and the titers of beta-glucan correlated well with the clinical efficacy of miconazole. The determination of beta-glucan appears to be useful for the diagnosis of deep mycosis.
Adolescent↗
Peroxidase-negative and myelomonocytic antigen-positive acute leukemia.
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.
Acid Phosphatase↗
A new animal model of non-insulin-dependent diabetes mellitus induced by the NDK25 variant of encephalomyocarditis virus.
Intraperitoneal inoculation with NDK25, a variant of Encephalomyocarditis (EMC) virus which has been newly cloned from the M variant of EMC virus (EMC-M), caused DBA/2 mice to develop noninsulin-dependent diabetes mellitus. The NDK25-infected mice demonstrated abnormal glucose tolerance from 1 to 3 weeks after inoculation. The infection resulted in mild insulitis and the destruction of pancreatic beta cells at 1 week after inoculation and led to a significant reduction in the insulin content of the pancreas, but there was no ketonuria. The insulin content of the pancreas was recovered considerably from 15 +/- 3 at 1 week to 95 +/- 16 micrograms/g pancreas at 12 weeks, although the latter value was still significantly lower than that of the control mice (P < 0.05). Under microscopy, mild and partial infiltration of mononuclear cells was observed in about half the pancreatic islets only 1 week after inoculation, and then disappeared. Thus, we believe we have established a new model of noninsulin-dependent diabetes mellitus using the NDK25 variant of EMC virus.
Animals↗
N-RAS activation in the terminal stage of undifferentiated chronic myeloproliferative disease.
The relationship between activation of the N-RAS gene and the leukemic progression of undifferentiated chronic myeloproliferative disease (UCMPD) was investigated in a 71-year-old male. Hematologically, it was difficult to differentiate the UCMPD from chronic myelogenous leukemia. Chromosomal analysis revealed no Philadelphia chromosome (Ph1-), and DNA analysis revealed no BCR rearrangement (BCR-) either at the beginning or in the terminal stages of the disease. We performed a tumorigenicity assay, using NIH3T3 cells, and molecular analysis, using the polymerase chain reaction (PCR) and direct sequencing. The DNA of leukemic cells at the beginning of the leukemic progression did not show any abnormalities, but at the terminal stage of the disease the DNA showed a point mutation in codon 12 (GGT----GCT) of the N-RAS gene. Interestingly, a codon 13 mutation (GGT----GTT) was also detected by tumorigenicity assay. These observations suggest that the activated N-RAS gene contributes to the hematologic progression of UCMPD.
Aged↗
A multicenter prospective study on the treatment of chronic idiopathic thrombocytopenic purpura.
A multicenter prospective study on the treatment of chronic idiopathic thrombocytopenic purpura (ITP) was conducted by the Idiopathic Disorders of Hematopoietic Organs Research Committee (IDHORC), the Ministry of Health and Welfare of Japan. The aim of the study was to establish an improved therapeutic guide for chronic ITP. Of the 247 eligible patients 175 have been followed up to the present time, 16 patients have died, and 56 have been lost to follow-up. The median follow-up time was 55 months (range: 1 to 91 months). Of the 206 patients treated with corticosteroids, 13.1% achieved sustained complete remission. Splenectomy produced remissions in 52.5% of 72 patients evaluated 12 months after operation. Eighty-five patients were treated with immunosuppressive agents, but the response rates were low and the effect was transient in most cases. In the patients followed up without any specific treatment, the mean platelet counts showed slight improvement. Of the 16 patients who died during the observation period, only one died of bleeding; the remaining 15 died of causes unrelated to thrombocytopenia. It is noteworthy that five patients who were treated with corticosteroids or immunosuppressive agents died of infection.
Adolescent↗
A possible correlation between the type of bcr-abl hybrid messenger RNA and platelet count in Philadelphia-positive chronic myelogenous leukemia.
The Philadelphia (Ph1) chromosome, in which the hybrid bcr-abl gene is formed, is thought to be the initial event in chronic myelogenous leukemia (CML). The position of the breakpoint within the breakpoint cluster region (bcr) on Ph1 chromosome and the splicing pattern determine the species of the fused bcr-abl messenger RNA (mRNA). We tried to detect the two types of fused mRNAs in 57 chronic-phase cases of Ph1-positive CML using the polymerase chain reaction procedure (RT-PCR). The bcr exon 2/abl exon 2 fused mRNA (b2-a2) was detected in 17 patients, the bcr exon 3/abl exon 2 fused mRNA (b3-a2) was detected in 34 patients, and both types of mRNA were detected in six patients. The platelet counts of patients who expressed b3-a2 mRNA or both types were significantly higher than those of patients who expressed only b2-a2 (841.5 v 373.5 x 10(9)/L; P less than .015), although there was no significant difference in the white blood cell counts or hemoglobin. This finding suggests a possibility that the type of bcr-abl mRNA may affect the thrombopoietic activity in CML.
Base Sequence↗
Transforming genes and chromosome aberrations in therapy-related leukemia and myelodysplastic syndrome.
The presence of activated transforming genes was investigated in four patients with therapy-related leukemia and in three with therapy-related myelodysplastic syndrome. DNA of bone marrow cells from six of the patients exhibited transforming activity in the tumorigenicity assay. Five of the six patients who were positive in the tumorigenicity assay contained activated N-ras oncogenes, and three contained activated K-ras oncogenes. Thus, concurrent activation of N-ras and K-ras oncogenes was observed in two patients. In vitro DNA amplification followed by oligonucleotide dot-blot analysis was used to investigate mutations in codons 12, 13, and 61 of the N-ras and K-ras oncogenes. Two patients exhibited an N-ras mutation, substituting aspartic acid (GAT) for glycine (GGT), and three patients exhibited an N-ras codon 13 mutation, substituting valine (GTT) for glycine. Two patients exhibited K-ras codon 12 mutations, substituting aspartic acid (GAT) or cysteine (TGT) for glycine (GGT), respectively, and one case exhibited a K-ras codon 61 mutation, substituting lysine (AAA) for glutamic acid (CAA). Cytogenetic analysis revealed that loss of chromosome 7 was frequent (four patients: 57%). Our data indicate that activation of N-ras and K-ras genes, as well as loss of heterozygosity for specific alleles on chromosome 7, plays a more important role in the leukemogenesis of both therapy-related leukemia and myelodysplastic syndrome.
Aged↗
The relationship between the site of breakpoints within the bcr gene and thrombopoiesis of Philadelphia-positive chronic myelocytic leukemia.
We determined the position of the breakpoint within the bcr gene in 22 patients with Philadelphia-positive chronic myelocytic leukemia using conventional Southern-blots and analyzed its relationship to thrombopoiesis. After DNA digestion with restriction endonucleases (Hind III, Bam HI and Bgl II), we localized the breakpoint in bcr using two genomic probes. The location of the breakpoint within the bcr was assigned to one of five zones. Breakpoints in zones 1 and 2 were grouped as "5"', and those in zones 3, 4 and 5 as "3'". Thus we subdivided patients with bcr rearrangements into those with genomic breaks at either 5' or 3' of the Bam HI site, just upstream of exon 3. Nine patients had 5' breakpoints and 13 patients had 3' breakpoints. The platelet counts of 3' patients were significantly higher than those of 5' patients (1395 vs 274 x 10(9)/l; p less than 0.03). The megakaryocyte counts from bone marrow histological sections in 3' patients (n = 12) and 5' patients (n = 7) were 63.4/mm2 and 19.5/mm2, respectively, with a significant difference of p less than 0.006. The mean number of megakaryocyte progenitor cells assayed by in vitro cloning was 128.3/2 x 10(5) bone marrow cells for 3' patients (n = 7) compared with 46.3 for 5' patients (n = 4). These results suggest that Philadelphia-positive CML patients with 3' breakpoints have higher thrombopoietic activity than patients with 5' breakpoints.
Adult↗
Cell-mediated cyclic thrombocytopenia treated with azathioprine.
We studied a male patient with cyclic thrombocytopenia whose bone marrow megakaryocyte count showed cyclic fluctuations in synchrony with cyclic changes of platelet count. He failed to respond to either prednisolone or bolus methylprednisolone therapy, but subsequently he was successfully treated with azathioprine. To investigate the underlying pathogenesis of the cyclic fluctuations in the platelet count, we studied the kinetics of megakaryocyte progenitor cells (CFU-Meg) and the effects of the patient's peripheral blood mononuclear cells on CFU-Meg. In one cycle of the platelet fluctuation, the increase in the CFU-Meg number preceded an increase in the bone marrow megakaryocyte count and then the platelet count. In the latter half of the cycle, CFU-Meg, bone marrow megakaryocytes and platelets began to decrease in that order. Peripheral blood mononuclear cells obtained from the patient in the thrombocytopenic phase suppressed megakaryocyte colony formation from normal bone marrow cells in a dose-dependent manner. In contrast, these cells obtained in the phase of a normal platelet count did not suppress megakaryocyte colony formation at all. These findings indicate that the cause of platelet fluctuation is periodic failure of megakaryocytopoiesis at the stage of CFU-Meg and that the patient's peripheral mononuclear cells are responsible for periodically suppressing the CFU-Meg.
Azathioprine↗
High-dose cytosine arabinoside as consolidation chemotherapy for acute nonlymphocytic leukemia in remission.
A controlled study was conducted to evaluate the efficacy of high-dose cytosine arabinoside (Ara-C) in consolidation therapy of acute nonlymphocytic leukemia in remission. Twenty-seven patients with acute nonlymphocytic leukemia during their first complete remission were divided into two groups. The high-dose Ara-C group (15 patients) received two courses of high-dose Ara-C and daunorubicin, i.e., 3 g/m2 of Ara-C IV over 1 h every 12 h eight times followed by 25 mg/m2 per day daunorubicin IV bolus for 2 days, and no maintenance chemotherapy. The control group (12 patients) received the conventional consolidation therapy (usually 7 days administration of 200 mg/m2 of behenoyl-arabino-furanosylcytosine and 2 to 3 days administration of 25 mg/m2 of daunorubicin) repeated every 3 to 4 months for more than 2 years. There were no significant differences in the duration of remission and survival between the two groups. It is suggested that high-dose Ara-C consolidation is worth employing in the treatment of acute nonlymphocytic leukemia because of its convenience for patients.
Adolescent↗
Two cases of disseminated Trichosporon beigelii infection treated with combination antifungal therapy.
Two patients with acute leukemia in whom disseminated Trichosporon beigelii infection developed are reported. The T. beigelii infection developed in the first patient while he was receiving 5-fluorocytosine. He was treated with amphotericin B in addition to 5-fluorocytosine. Despite the continued antifungal therapy, multiple organs were invaded by the organisms at autopsy. The second patient was treated with miconazole and norfloxacin. Although this combination antifungal therapy seemed to be effective, this patient required splenectomy for cure of the infection.
Adult↗
Pure red cell aplasia following pernicious anemia.
A rare case of pure red cell aplasia (PRCA) in association with pernicious anemia is reported. A 40-year-old man presented with typical clinical and laboratory features of pernicious anemia and received intramuscular injections of vitamin B12, with satisfactory response. Anemia recurred 6 months later despite continued therapy, and the patient was noted to have PRCA, which was treated successfully with two courses of high-dose bolus methylprednisolone therapy. His peripheral mononuclear cells before the therapy suppressed colony formation of early erythroid precursors (BFU-E) from normal bone marrow; such a suppressive effect was not found after recovery from anemia.
Adult↗
Anti-thoracic duct lymphocyte globulin stimulates human megakaryocytopoiesis in vitro.
Anti-thoracic duct lymphocyte globulin (ALG) therapy is effective in patients with aplastic anemia. We examined the effect of ALG on human megakaryocyte progenitor cells (colony-forming unit-megakaryocyte, CFU-Meg) in vitro. Normal human bone marrow mononuclear cells (MNC) were cultured in plasma clots with varying concentrations of ALG or non-immunized horse IgG. After 12 days of culture, significant megakaryocyte colony formation was observed in cultures containing ALG but not in cultures containing non-immunized horse IgG. The peak stimulatory effect seemed to occur with 10-25 micrograms/ml of ALG. When marrow MNC, depleted of adherent and T cells, were cultured in plasma clots with ALG, its stimulatory effect on megakaryocytopoiesis decreased markedly. Finally, it was demonstrated that ALG stimulated marrow MNC to produce a factor stimulatory for CFU-Meg. The in vitro megakaryocytopoietic stimulatory effect of ALG may be related to its clinical efficacy in some patients with aplastic anemia.
Antilymphocyte Serum↗
Kinetics of megakaryocyte progenitor cells in idiopathic thrombocytopenic purpura.
The number and proliferative state of megakaryocyte progenitor cells (CFU-Meg) were compared between 13 patients with idiopathic thrombocytopenic purpura (ITP) and hematologically normal controls. The mean frequency of CFU-Meg assayed by the plasma clot method was 27.8 +/- 12.2 (+/- SD)/2 x 10(5) bone marrow light-density cells for the ITP patients, which did not differ significantly from the control value of 31.9 +/- 16.1. The percentage of CFU-Meg in DNA synthesis estimated by the 3H-thymidine suicide technique was 41.3% +/- 9.2% in ITP, which was significantly greater than the control value of 27.1% +/- 7.4% (P less than 0.01). The megakaryocyte counts for histological sections prepared from bone marrow aspirates from the ITP patients and controls were 34.5 +/- 8.5/mm2 and 11.2 +/- 5.8/mm2, respectively, with the difference being highly significant (P less than 0.001). These results suggest that increased cycling activity in a quantitatively unchanged CFU-Meg pool may lead to increased megakaryocytes in the bone marrow of ITP patients.
Bone Marrow↗
Attachment of one spindle pole to the cortex in unequal cleavage.
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Animals↗