[Hairy cell leukemia; its place in B cell differentiation and the function of hair cells].
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B-Lymphocytes↗
Biomedical subjects
T Kitani
Publications and source records attributed to T Kitani.
Successful treatment of Diphyllobothrium latum and Taenia saginata infection by intraduodenal 'Gastrografin' injection.
Tapeworm infections are very difficult to cure completely. Thirteen patients with tapeworm infection, seven with Diphyllobothrium latum and six with Taenia saginata, were treated by the introduction of a radio-opaque contrast medium, 'Gastrografin', into the duodenum through a duodenal tube. The whole tapeworm with the scolex was expelled unfragmented within 1 h in eleven cases. One patient expelled a tapeworm 3 days after treatment; the peristalsis of his intestine had been severely disturbed after an attack of cerebral apoplexy. The tapeworm could not be expelled by the remaining patient, probably because she had severe intestinal adhesion. The injection of gastrografin allowed clear visualisation of the tapeworm, the diagnosis of the infection could be confirmed, and the descent of the tapeworm could be observed serially. This treatment had no serious adverse effects in any of out patients.
Adult↗
alpha-Difluoromethylornithine does not bind to ornithine decarboxylase-antizyme complex.
alpha-Difluoromethylornithine (DFMO) has been widely used for determining the amounts of ornithine decarboxylase (ODC) in cells. However, we have now found that DFMO does not react with ODC-antizyme complex, indicating that the amounts of radioactive DFMO bound to the protein may not reflect the amounts of ODC in crude tissue extracts.
Animals↗
OKM1-positive T-cell leukemias. Relationships among morphologic features, phenotype, and functional activities.
The morphologic features, phenotype, and functions of OKM1+ leukemic T-cells were studied. The leukemic T-cells in two patients with chronic lymphocytic leukemia (CLL) had specific features of large granular lymphocytes (LGL), and those in two patients with acute lymphocytic leukemia (ALL) had L2 morphologic characteristics. The phenotype of the leukemic cells from one patient with CLL was OKM1+, ER+, OKT3+, OKT4+, OKT8-, OKIa1-, IgGFc receptor (EA gamma)+, Leu-7+, Leu-11b+, and anti-Tac-. The cells had antibody-dependent cell-mediated cytotoxicity (ADCC), but no natural killer (NK) activity. They had a definitive helper effect on pokeweed mitogen-induced normal B-cell differentiation. The leukemic cells from the other patient with CLL were Leu-7-, and Leu-11b-, and lacked both ADCC and NK activity. The leukemic cells in the two patients with ALL were ER+, OKM1+, Leu-7-, and Leu-11-, and did not have any cytotoxicity. One was EA gamma +, and the other was EA gamma -. These findings suggest that OKM1+ leukemic T-cells consist of at least two subgroups: (1) T-cells with the morphologic features of LGL; and (2) those with a lymphoblastic morphologic type. In either case, the phenotype is novel and suggests the emergence of a small, distinct lymphocyte subset.
Acid Phosphatase↗
Distribution of Gc protein (vitamin D binding protein) on the surfaces of normal human lymphocytes and leukemic lymphocytes.
Distribution of membrane-bound Gc protein (mGc) in normal lymphocyte subpopulations and leukemic lymphocytes was studied using a rabbit antiserum specific to Gc protein. Forty to fifty percent of the normal peripheral blood mononuclear cells were stained with anti-Gc antiserum by membrane immunofluorescence, and almost all of the B cells (B1+) and NK cells (Leu 11+) were mGc-positive. Only a few resting T cells (T3+) reacted with anti-Gc, but mGc appeared in a significant number of the T cells after activation by PHA. The distribution of mGc on leukemic lymphocytes of various types nearly corresponded to that in normal lymphocyte subpopulations.
B-Lymphocytes↗
Leu 11+ T gamma cell chronic lymphocytic leukemia with partially activated natural killer function and its further activation by recombinant IL2 in vitro.
A patient with T gamma cell chronic lymphocytic leukemia with the Leu 11+ phenotype and novel function of activated natural killer cells is reported. The peripheral blood mononuclear cells of this patient showed large granular lymphocytes by May-Giemsa staining and lamellipodia by scanning electron micrography. Tests on reactivity with monoclonal antibodies showed that most cells were Leu 11+, OKT3-/Leu 1-, OKT4-, OKT8-, Leu 7-, OKM1-, and Tac-. Freshly collected cells lysed not only K562, which is highly sensitive to natural killer cells, but also Raji cells and Daudi cells, which are not. Leu 11+ cells were triggered by recombinant interleukin 2 (rIL2) to proliferate, produce gamma-interferon (gamma IFN), and show enhanced HLA-DR antigen expression, and 30% of the Leu 11+ cells became positive for IL2 receptor antigen (Tac). The spectrum of cytotoxic activity of these cells against target cells was extended by rIL2; after treatment with rIL2, the cells also lysed HeLa cells and even fresh cancer cells. This stimulation also increased the activities of acid phosphatase and tartrate-resistant acid phosphatase of the cells and resulted in the appearance of nonspecific esterase activity. The expanded cell population may represent a neoplasm, but these findings provide information on a novel differentiation stage of activated NK cells.
Aged↗
Mitogenic response of neoplastic B cells: comparison of reactivity to Staphylococcus aureus Cowan I and anti-immunoglobulin antibodies.
Neoplastic B cells from two patients with hyperleucocytic hairy cell leukaemia (HCL) and 19 patients with chronic lymphocytic leukaemia of B cell Type (B-CLL) were investigated to examine the mitogenic responses to the F(ab')2 fraction of anti-human immunoglobulins (anti-Igs) and Staphylococcus aureus Cowan I (STA). Neoplastic cells from both HCL patients lacked surface Tac antigen. Mononuclear cells from the two HCL patients strongly responded to both anti-Igs and STA as measured by 3H-thymidine incorporation in vitro. Although the mononuclear cells from two patients with B-CLL showed high response to STA, cells from none of the patients with B-CLL responded to anti-Igs. Mononuclear cells as well as T-cell-depleted fractions from the two HCL patients showed a strong proliferative response by anti-gamma chain antibody (anti-gamma) and the mononuclear cells from one of the patients were also induced to proliferate by anti-delta, whereas those from normal subjects responded only to a high concentration of anti-mu. Based on the difference in reactivity to anti-Ig, it is suggested that the HCL cells in this study originate from a subset equivalent to 'memory' B cells, whereas the B-CLL cells originate from a subset equivalent to 'virgin' B cells.
Antibodies, Anti-Idiotypic↗
[Effect of low-dose Ara-C in the treatment of refractory, atypical leukemia and myelodysplastic syndrome].
This study was designed to evaluate the effect of low-dose Ara-C in the treatment of refractory, atypical leukemia and myelodysplastic syndrome (MDS). The subjects were 33 patients (19 acute myelocytic leukemia (AML), 9 MDS, 3 atypical leukemia and 2 unclassified leukemia). The age range was 19 to 84 years with a mean age of 51.5 years. We administered low-dose Ara-C (5-10 mg/m2/12 h s.c. or i.v.) for 13 to 35 days with a mean of 16.7 days. Complete remission and partial remission were obtained in 8 of 31 (25.8%) and in 9 of 31 (29.0%) respectively. A high response rate was found in M2 types showing a tendency for mature and refractory anemia with excess blasts in MDS according to the FAB classification. In our cases, severe pancytopenia in peripheral blood as a result of Ara-C was observed before normal hematopoiesis recurred. From the above results, the mechanism of low-dose Ara-C may induce remission by a cytotoxic rather than a differentiation effect. This treatment can be offered to patients with refractory, atypical leukemia and MDS with limited toxicity.
Adolescent↗
[Phase II study on oral administration of MCNU (ranomustine) tablet. Hanshin Cooperative Study Group on Hematological Disorders].
A phase II study of MCNU tablet has been performed on 70 patients with hematological disorders including mostly myeloproliferative disorders. MCNU tablet was given p.o. at a dose of 50 mg daily for 2-6 days (total 100-300mg) as one course with average intervals of 3 to 5 months or more for patients responding to this drug. The effective rates were 72% in 18 patients with chronic myelogenous leukemia, 88% in 25 patients with polycythemia vera and 68.5% in 19 patients with essential thrombocythemia. Side effects of MCNU tablet were nausea and vomiting (31%) which had a dose-dependent relationship, mild liver dysfunction (5%) and elevation of BUN and creatinine (2%) which were not serious. The results were almost comparable to those of the phase II study of MCNU given intravenously.
Administration, Oral↗
[Phase II trial of mitoxantrone in patients with relapsed and refractory acute leukemia].
Mitoxantrone, a new anthracenedione, was administered to thirty-nine patients with relapsed and refractory acute leukemia and to 12 patients with blastic crisis of chronic myelogenous leukemia between August 1981 and September 1984. Eleven patients were not evaluable and 40 were analysed. There were 24 males and 16 females with a median age of 37 yrs (range 6-73 yrs). Three of these were less than 15 yrs and 7 more than 60 yrs. The initial dose employed was 1.9 mg/m2/day X 5. Although eventually a starting dose of 12.3 mg/m2/day X 5 was used, about one half of cases were given more than 5 mg/m2/day X 5 by i.v. bolus. Among 25 patients with acute non-lymphocytic leukemia, there were 4 complete and 6 partial remissions. Among 7 patients with acute lymphocytic leukemia there was one complete remission and one partial remission. All patients except one who attained remissions had received prior anthracyclines. One of 8 patients with blastic crisis of chronic myelogenous leukemia had a partial remission. The durations of complete remission were 1, 1, 5+, 13+ and 17 weeks, respectively. Side-effects showed expected bone marrow depression. Mucositis occurred in ten patients. Gastrointestinal symptoms were noted in approximately 50%, but were mostly mild. Mild alopecia occurred occasionally. The trials were too short to allow evaluation of possible cardiac toxicity. These data indicate that mitoxantrone is non-toxic but hematological and a promising single drug for use in treating relapsed and refractory acute leukemia and suggest that further study would be worthwhile in order to identify its role in the first-line therapy of acute leukemia.
Aclarubicin↗
[A phase III study of BHAC-MMP (behenoyl-ara-C, mitoxantrone, 6-mercaptopurine prednisolone) in acute leukemia. Hanshin Cooperative Study Group of Hematological Disorders].
BHAC-MMP therapy, a combination of behenoyl-ara-C, mitoxantrone, 6-mercaptopurine and prednisolone, was applied to 49 patients with acute leukemia for remission induction. Complete remission was obtained in 6 out of 11 previously untreated patients (55%), and in 16 of 38 pretreated patients (42%). Median duration of complete remission was 41 weeks in previously treated patients, while 67% of untreated patients were still in complete remission. Most frequent side effects other than hematological toxicities were gastrointestinal disturbances, and GPT elevation etc., although most of these were not severe. In conclusion, BHAC-MMP therapy seems to be very promising for remission induction or for possible intensification treatment for acute leukemia.
Acute Disease↗
[A phase II study of mitoxantrone in acute leukemia. Hanshin Cooperative Study Group of Hematological Disorders].
A phase II study of mitoxantrone was conducted on acute leukemia. Mitoxantrone 4 mg/m2/day was administered for 5 consecutive days in most cases. For cases showing insufficient decrease of leukemic cells even at nadir, a second course of the same regimen was given. Enrolled were 38 cases in total, of which 34 were evaluable. In 14 cases for first remission induction, the drug efficacy was evaluated at the completion of the first or second course, then further combination drug therapy followed immediately. Of 14 cases for first remission induction, 6, or 43%, achieved CR and of 20 cases for reinduction of remission, 4, or 20%, achieved CR. Two out of 7 cases of ALL (29%) and 8 out of 27 cases of ANLL (30%) achieved CR. Of 19 cases with previous anthracycline therapy, 4 cases, or 21%, achieved CR, showing that the cross-resistance was partial. Gastrointestinal symptoms were the main side effects, but cases of symptoms severer than grade 3 were very rare. Cardiotoxicity occurred at a rate as low as 11%. Mitoxantrone thus appears to be a promising drug for the treatment of acute leukemia.
Acute Disease↗
[A phase II study of mitoxantrone in refractory and relapsed malignant lymphomas. Cooperative Study Group of Mitoxantrone in Malignant Lymphomas].
A phase II clinical trial of mitoxantrone in refractory or relapsed malignant lymphomas was conducted by a cooperative study involving 17 institutions. Of 46 patients entered, 33 were evaluable for responses and toxicity. Thirty-one of the 33 had been previously exposed to adriamycin at a median dose of 220 mg/m2 (range 21-489 mg/m2), and two additional patients had each been given THP-adriamycin at a dose of 80 mg/m2 or 4'-epi adriamycin at a dose of 69 mg/m2. Mitoxantrone was administered in 3 different schedules: 8-12 mg/m2, every 3-4 weeks in 23 patients; 4-6 mg/m2, weekly, in 3 patients; and 2-4 mg/m2, for 5 days, in 7 patients. Summarizing the responses obtained in the 3 schedules, there were 2 partial responders among 5 with Hodgkin's disease, while there were 8 complete responders and 4 partial responders among 28 with non-Hodgkin's lymphoma. The overall response rate for all the evaluable patients was 42% with a complete response rate of 24%. The median response duration was 7+ weeks (range 4-27+ weeks) for complete responders and 7 weeks (range 4-46+ weeks) for partial responders. The major toxicity was myelosuppression: leukocytopenia less than 3,000/microliter occurred in 79% of patients, and thrombocytopenia less than 75,000/microliter in 35%. Other toxic effects were minimal, mild nausea and/or vomiting occurred in 39%, and diarrhea in 3%. Possible drug-related liver and renal dysfunctions were observed in 19% and 10%, respectively. The favorable response to mitoxantrone in patients with prior anthracycline antibiotic therapy suggests that the drug is not fully cross-resistant with anthracycline antibiotics, and that this drug is of value in combination with other drugs as a salvage therapy for patients with refractory or relapsed malignant lymphomas.
Adolescent↗
Association of specific tyrosine phosphorylation with stages of B-cell differentiation in human lymphoid leukemias.
In vitro protein phosphorylation in various types of human fresh lymphoid leukemic cells (C-ALL, B-CLL, HCL and PCL: B-cell lineage and T-ALL, ATL and T-CLL: T-cell lineage) were studied. In cases of B-CLL and HCL, tyrosine protein kinase (TPK) activity was at least 5-fold higher than that in other cases of B- and T-cell lineages. B-cell leukemic cells at various differentiation stages had different endogenous substrates in tyrosine phosphorylation as well as distinct TPK activity. The P-tyr-containing proteins of 68K, 59K and 56K were detected commonly in all the cases of B-cell lineage. The phosphorylated protein of 32K was present only in cases of PCL. On the other hand, in T-ALL and ATL, the major substrate in tyrosine phosphorylation was 58K. These results suggest that the characterization of in vitro tyrosine phosphorylation provides a new means not only to distinguish T- and B-lymphoid leukemia, but also to differentiate stages of lymphoid development.
B-Lymphocytes↗
Evidence that discontinuous DNA replication in Escherichia coli is primed by approximately 10 to 12 residues of RNA starting with a purine.
Intact primer RNA for discontinuous DNA replication of Escherichia coli has been detected by specific labeling in vitro of its 5'-terminal tri- (or di-) phosphate group with vaccinia guanylyltransferase and [alpha-32P]GTP. A mutant defective either in RNase H or in both RNase H and DNA polymerase I accumulated about 10 or 30 times more intact primer RNA, respectively, than wild-type cells. The primers started with purine in an A to G ratio of 5 and the most abundant 5'-terminal dinucleotide sequence was (p)ppA-Pu. The chain length of the intact primer RNA was approximately 10 to 12 nucleotide residues. The structural properties of the E. coli primer RNa resemble those of the eukaryotic primer RNA.
Base Sequence↗
A phase II study of mitoxantrone in acute leukemia.
A phase II study of mitoxantrone (Novantrone; dihydroxyanthracenedione) was conducted in 35 patients (22 male: 13 female) with acute leukemia. There were 35 evaluable cases with a mean age of 34 (range 8-61). Twenty-eight patients had acute non-lymphocytic leukemia (ANLL) and seven had acute lymphocytic leukemia (ALL). Mitoxantrone was administered intravenously 2-4 mg/m2 daily for five days and after the nadir a further 2-3 doses were added if necessary. All previously treated cases (22 patients) had been treated with anthracyclines; 13 had no previous treatment. Out of the 13 untreated cases there were six complete remissions (CRs) (46.2%) and five partial remissions (PRs) (38.5%), while out of 22 pretreated cases, four CRs (18.2%) and five PRs (22.7%) were obtained. In seven of the untreated cases the decrease of leukemic cells and neutrophil leukocytes were analysed. Mitoxantrone showed a longer duration of decrease and higher log decrease of leukemic cells in the bone marrow than daunorubicin or cytosine arabinoside. Seventy-three percent of patients showed gastrointestinal disturbances such as nausea or loss of appetite. In 38.1% SGPT elevation and in 8.8% abnormal ECG findings were observed. All side-effects were mild and reversible. From this data mitoxantrone seems a very promising agent in the treatment of acute leukemia and a phase III study is now being carried out.
Aclarubicin↗
Serum immunosuppressive acidic protein in adult T-cell leukaemia (ATL).
The availability of serum immunosuppressive acidic protein (IAP) as a marker of subtypes of adult T-cell leukaemia (ATL) was examined. Serum IAP levels were measured in 34 patients with ATL (18 typical, 9 atypical and 7 smoldering), 7 healthy carriers of ATLA antibody and 53 healthy controls. The mean value of serum IAP was significantly higher in patients with typical ATL (897.8 +/- 502.4 micrograms/ml) than in those with atypical ATL (426.7 +/- 106.6 micrograms/l), smoldering ATL (310.0 +/- 51.3 micrograms/ml), healthy carriers of ATLA antibody (302.9 +/- 39.5 micrograms/ml) and normal controls (350.5 +/- 73.2 micrograms/ml). Serial determinations of IAP revealed that the level was correlated with the clinical course in patients with ATL; there was a difference in the prognosis of patients with high and normal levels of IAP (P less than 0.05). Thus, routine measurement of serum IAP seems useful in differentiating typical, atypical and smoldering ATL and also in evaluating the prognosis of patients.
Adult↗