The Japanese experience in various institutions.
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Humans↗
Biomedical subjects
A Urabe
Publications and source records attributed to A Urabe.
Interstitial pneumonia in patients receiving granulocyte colony-stimulating factor during chemotherapy: survey in Japan 1991-96.
Twenty cases of interstitial pneumonia secondary to treatment with granulocyte colony-stimulating factor (G-CSF) were reviewed. Their interstitial pneumonia had the following features: (a) it occurred predominantly in patients aged 60 years or older; (b) it was prevalent among patients with haematological malignancies, particularly non-Hodgkin's lymphoma; (c) in all patients G-CSF was given after anti-cancer agents with potential to affect the lungs; (d) at the onset, many patients had symptoms such as dyspnoea and fever; and (e) the leucocyte (neutrophil) count as well as lactate dehydrogenase (LDH) and C-reactive protein (CRP) levels were usually higher than normal at the onset. These findings indicate that, when G-CSF is used in combination with pneumotoxic anti-cancer agents, respiratory function should be monitored before and during treatment. If the leucocyte (or neutrophil) count and/or LDH and CRP increase suddenly in association with dyspnoea and fever during administration of G-CSF, interstitial pneumonia should be suspected. Accordingly, a chest radiograph and pulmonary functional tests should be performed promptly. If a diagnosis of interstitial pneumonia is made, steroid pulse therapy should be commenced immediately.
Adult↗
Influence of thrombopoietin on platelet activation in myeloproliferative disorders.
Although thrombopoietin itself does not influence platelet aggregation, it enhances platelet activation in response to certain agonists. We evaluated the effects of thrombopoietin on platelet activation using platelet-rich plasma from 16 patients with myeloproliferative disorders (MPD group) and 16 healthy volunteers (control group). Preincubation with thrombopoietin significantly enhanced platelet aggregation stimulated by ADP, collagen, or epinephrine in the MPD group as well as the control group. However, aggregation induced by 3 micro ADP or 16 microM epinephrine showed significantly less augmentation by thrombopoietin in the MPD group than in the control group. Thrombopoietin significantly shortened the lag time between the addition of 3 microM ADP or 16 microM epinephrine and initiation of secondary aggregation and the lag time between addition of 2 microg/ml collagen and initiation of aggregation in both groups. When platelet-rich plasma was used without adjustment of the platelet count, thrombopoietin itself induced aggregation in two patients. Hypoaggregation after addition of 0.5 microg/ml collagen was observed in seven out of nine patients with normal thrombopoietin levels and only one of six patients with high levels (P = 0.04). Enhancement of 0.5 microg/ml collagen-induced aggregation by thrombopoietin was seen in five out of nine patients with normal thrombopoietin levels and none of the six patients with elevated levels (P = 0.04). These results indicate that platelet activation by certain agonists is enhanced by thrombopoietin in patients with these diseases as well as in normal controls and that the serum thrombopoietin level may regulate the function of circulating platelets in vivo.
Enzyme-Linked Immunosorbent Assay↗
Cyanamide-induced granulocytopenia.
We report a 64-year-old male with granulocytopenia and dermatitis due to cyanamide treatment. We administered cyanamide for alcoholism. After about one month he suffered from scaly erythema over his whole body and granulocytopenia (granulocyte; 140/microliter) with maturation arrest in bone marrow. After cessation of cyanamide and the start of granulocyte colony-stimulating factor administration, the skin eruption ameliorated gradually, and the peripheral blood granulocyte counts increased. Cyanamide showed positive results in the drug lymphocyte stimulation test (198%) and the patch test led to the diagnosis of granulocytopenia and dermatitis induced by cyanamide. After restarting glibenclamide and diazepam administration, his granulocytopenia did not reoccur. To our knowledge, this is the first report of a case with granulocytopenia induced by cyanamide.
Agranulocytosis↗
Oblique axial and oblique coronal MR imaging of the proximal femur.
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Aged↗
Increased neutrophil respiratory burst in myeloproliferative disorders: selective enhancement of superoxide release triggered by receptor-mediated agonists and low responsiveness to in vitro cytokine stimulation.
The neutrophil superoxide (O2-)-producing capacity in 57 patients with chronic myeloproliferative disorders (MPDs) and eight patients with chronic myelomonocytic leukemia (CMML) was investigated. O2- release in neutrophils stimulated by chemotactic peptide was markedly increased in all types of chronic MPD, including chronic myelogenous leukemia in both chronic phase and blastic crisis, polycythemia vera, and essential thrombocythemia, but was normal in CMML, which is thought to be a myelodysplastic disorder rather than MPD. Increase in O2(-)-producing capacity in MPD was also observed when other receptor-mediated agonists such as interleukin-8 and concanavalin A were used, but not when phorbol ester, a direct activator of protein kinase C, was used as the triggering agonist of O2- release. Priming effects of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF), and tumor necrosis factor (TNF) on chemotactic peptide-induced O2- release was observed in all patients with MPD and CMML, though fold enhancement of priming effects was much less in MPD compared with normal subjects. In addition, the priming effects of TNF were less than those of GM-CSF in 10 cases, whereas the priming effects of TNF were consistently and markedly greater than those of GM-CSF in normal subjects. Tyrosine phosphorylation of 42-kDa protein stimulated by G-CSF, GM-CSF, and TNF was observed in CML neutrophils to be identical to that in normal neutrophils. Present results indicate specific potentiation of the receptor-mediated route of signaling that is linked to the respiratory burst and downregulated responsiveness to cytokines in neutrophils in patients with all types of chronic MPD, suggesting in vivo priming of patient neutrophils via certain mechanism by cytokines or related stimuli in these hematological disorders.
Concanavalin A↗
[False positive FDP test associated with malignant lymphoma].
We present a man with non-Hodgkin's lymphoma who had false positive FDP test results and who had monoclonal IgM and IgG. At admission, laboratory examinations showed elevated FDP levels and prolonged PT and APTT, which did not improve by anti-coagulation therapy. Although coagulation system data returned to normal levels after steroid pulse therapy, the FDP level increased. Positive pregnancy test and results of dilution analyses on FDP assay yielded a diagnosis of false positive FDP test results due to serum latex agglutinin. The addition of anti-immunoglobulin antibody inhibited latex agglutination by serum. FDP levels positively correlated with serum IgM concentrations. These data suggest that the false positive FDP test in this case was due to latex agglutination by monoclonal IgM.
Connectin↗
[Hematopoietic factors: serum concentrations and clinical application].
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Erythropoietin↗
[Recent progress in therapy for chronic myelogenous leukemia].
In chronic myelogenous leukemia (CML), abnormalities develop in hematopoietic stem cells, affecting three hematopoietic cell series, including leukocytes, erythrocytes, and platelets. The occurrence of the Philadelphia (Ph1) chromosome and BCR/ABL fused genes are involved in its pathophysiology. Methods of treating CML consist of bone marrow transplantation, and administration of interferon (IFN) and other antineoplastic drugs. Bone marrow transplantation is strongly recommended when the patient is young (usually aged 45 years or younger) and a donor with identical human leukocyte antigens (HLA) is available. When bone marrow transplantation is impossible, administration of IFN is the treatment of choice. IFN administration may induce disappearance or a decrease in the Ph1 chromosome. IFN administration has been demonstrated to significantly increase the survival rate over conventional chemotherapy (hydroxyurea or busulfan).
Age Factors↗
Serum thrombopoietin level in various hematological diseases.
To investigate the pathophysiological role of thrombopoietin (TPO) in thrombopoiesis, we measured its serum levels in 15 healthy individuals, 84 patients with various hematological diseases and 2 patients with liver cirrhosis using an enzyme immunoassay procedure. The TPO level was 0.84 +/- 0.40 f mol/ml in normal individuals. TPO levels were considerably elevated in patients with myelosuppression after intensification chemotherapy of acute leukemia in complete remission (postchemotherapy group; n = 18; 18.46 +/- 9.70 f mol/ml). When the data of normal individuals and the postchemotherapy group were combined, TPO levels were inversely correlated with the platelet count in this combined group. We compared these data of normal individuals and the postchemotherapy group with various hematological disease states. In aplastic anemia (n = 13; 16.03 +/- 9.44 f mol/ml), acute lymphoblastic leukemia (n = 5; 10.36 +/- 5.57 f mol/ml), malignant lymphoma (n = 6; 2.79 +/- 2.27 f mol/ml), multiple myeloma (n = 3; 3.34 +/- 0.20 f mol/ml) and chronic lymphocytic leukemia (n = 2; 1.71 +/- 3.91 f mol/ml), the relationship of serum TPO levels and platelet counts was almost the same as in the combined group with normal individuals and the postchemotherapy group. However, the TPO levels were slightly higher in myeloproliferative disorders (n = 12; 1.99 +/- 1.47 f mol/ml) and lower in acute myelogenous leukemia (n = 8; 2.27 +/- 1.25 f mol/ml), hypoplastic leukemia (n = 3; 2.76 +/- 2.23 f mol/ml), myelodysplastic syndrome (n = 2; 0.42 +/- 0.60 f mol/ml), liver cirrhosis (n = 2; 1.50 +/- 0.92 f mol/ml) and idiopathic thrombocytopenic purpura (n = 12; 2.08 +/- 1.41 f mol/ml), when compared to the regression line for the combined group with normal individuals and postchemotherapy group. These findings suggest that TPO might play an important role in regulation of the platelet count in normal and pathological conditions.
Adult↗
Differentiation effect of acyclic retinoid on acute promyelocytic leukemia cells.
Acyclic retinoid (all-trans-3, 7, 11, 15-tetramethyl-2, 4, 6, 10, 14-hexadecapentaenoic acid) binds cellular retinoic acid-binding protein with an affinity similar to that of all-trans retinoic acid and induces differentiation of human hepatoma cell lines and a human acute myelogenous leukemia cell line (HL-60). We investigated the in vitro efficacy of acyclic retinoid to induce the differentiation of acute promyelocytic leukemia (APL) cells using primary cultured cells obtained from 11 APL patients. Five days' incubation with acyclic retinoid effected a dose-dependent induction of differentiation. Cells from eight patients showed maximum differentiation at 10(-6) M acyclic retinoid. Cells from one patient required 10(-5) M for maximum differentiation, while those from two patients exhibited moderate differentiation at 10(-5) M. Five days' incubation with acyclic retinoid (10(-7) approximately 10(-5) M) did not affect the viability or number of cells from any patient except one, whose cells showed a slight decrease in viability at 10(-5) M. Thus, we conclude that acyclic retinoid induced the differentiation of primary cultured APL cells at concentrations of 10(-6) approximately 10(-5) M, a range at which it is not toxic.
Antineoplastic Agents↗
Pharmacokinetics of all-trans-retinoic acid in Japanese patients with acute promyelocytic leukemia.
All-trans-retinoic acid (ATRA) was administered at 45 mg/m2 to 4 Japanese patients with acute promyelocytic leukemia (APL). A pharmacokinetic study revealed that the mean peak plasma concentration was 208 ng/ml and was reached at 150 min after ingestion. The mean area under the concentration x time curve (AUC) was 498 ng.h/ml. Two patients showed a good hematological response to ATRA, and they had higher peak plasma concentrations of ATRA and larger AUCs. In one patient, dose escalation of ATRA (90 mg/m2) increased the plasma concentration markedly. In another patient, the plasma concentration decreased markedly in the fasting state. A larger pharmacokinetic study is necessary to examine the influence of food on the absorption of this agent and an optimum administration schedule of ATRA in Japanese APL cases.
Adult↗
Administration of granulocyte colony-stimulating factor during remission induction therapy with all-trans retinoic acid for acute promyelocytic leukemia.
Granulocyte colony-stimulating factor (G-CSF) enhances the differentiation of acute promyelocytic leukemia (APL) cells induced by all-trans retinoic acid (ATRA) in vitro. Accordingly, we initiated a pilot study on G-CSF in APL patients who developed neutropenia and severe infection during remission induction therapy with ATRA. Seven out of nine treated patients displayed a marked increase in granulocyte counts without leukemic regrowth, and two displayed a dramatic decrease in leukemic blasts. However, leukemic regrowth occurred in two patients under treatment for post-ATRA relapse. Our findings suggest that administration of G-CSF combined with ATRA can improve the hematological state in APL patients not previously receiving ATRA therapy.
Adult↗
A sensitive sandwich ELISA for measuring thrombopoietin in human serum: serum thrombopoietin levels in healthy volunteers and in patients with haemopoietic disorders.
A sensitive sandwich enzyme-linked immunosorbent assay (ELISA) has been established to estimate serum thrombopoietin (TPO) concentrations in healthy volunteers and patients with haemopoietic disorders. The ELISA uses a mouse monoclonal antibody (Ab) as the capture Ab and a biotinylated rabbit polyclonal Ab as the detector. The ELISA was reproducible, highly sensitive and specific for human TPO. The coefficients of intra-and inter assay variation were from 3.0% to 4.9% and from 5.9% to 6.1%, respectively. The quantitative limit of the ELISA was 0.09 fmol/ml in serum. The quantitative limit was lower than the normal level. The dose-response curves of serum samples from healthy volunteers and patients with haemopoietic disorders were parallel to the standard curves. The ELISA did not cross-react with a variety of blood components and cytokines to produce false-positive results. The serum TPO concentrations from 29 normal males and 21 females were 0.79 +/- 0.35 and 0.70 +/- 0.26 fmol/ml, respectively. Serum TPO levels in patients with aplastic anaemia (AA), acute lymphocytic leukemia (ALL) and essential thrombocythaemia (ET) were measured using the ELISA. The serum TPO levels in the patients with ET (n = 6, 2.80 +/- 1.55 fmol/ml) were higher than the normal level. The patients with AA (n = 7, 18.53 +/- 12.37 fmol/ml) and ALL (n = 5, 10.36 +/- 5.57 fmol/ml) had significantly higher serum TPO levels than normal individuals. These results indicate that the ELISA specific to TPO should prove useful in measuring the TPO concentration in serum samples.
Adult↗
Hair cortex comedo.
We report two cases of skin lesions that clinically resemble a comedo. Both lesions demonstrated a firm black papule which was histopathologically reminiscent of a dilated hair follicle associated with an abnormality of the hair cortex. These findings are thus considered to represent a unique and peculiar variant of the dilated pore of Winer, and the term "hair cortex comedo" is therefore believed to be suitable for such lesions.
Acne Vulgaris↗
Effect of recombinant human granulocyte colony-stimulating factor on combination therapy with aztreonam and clindamycin for infections in neutropenic patients with hematologic diseases.
The present multicenter study was performed to evaluate the effect of recombinant human granulocyte-colony stimulating factor (rhG-CSF) on combination therapy using aztreonam (AZT) and clindamycin (CLDM) to treat severe infection in neutropenic patients with hematologic diseases. Forty-three neutropenic patients with infections (rhG-CSF group) were treated with AZT (2 g) and CLDM (600 mg) 2-3 times daily as well as rhG-CSF (Lenograstim or Filgrastim: 2-5 mu/kg/day). The clinical efficacy of this regimen was compared to that obtained in 44 febrile neutropenic patients, with hematologic diseases, who received only AZT and CLDM in a previous study (historical control group). The overall efficacy rate was 69.8% (30/43) in the rhG-CSF group and 65.9% (29/44) in the historical control group. Although the neutrophil count was significantly increased and C-reactive protein tended to be lower in the rhG-CSF group, the daily maximum body temperature profiles of the 2 groups were nearly the same. These results suggest that rhG-CSF is of little benefit in the treatment of single infectious episodes in neutropenic patients, and that appropriate antibiotic therapy is more important.
Acute Disease↗
CBFB/MYH11 fusion transcripts in a case of acute myelogenous leukemia (M1) with partial deletion of the long arm of chromosome 16.
Pericentric inversion of chromosome 16 [inv(16)(p13q22)] is seen in patients with acute myelomonocytic leukemia with bone marrow eosinophilia. This inversion juxtaposes the MYH11 gene on p13 and the CBFB gene on q22, resulting in the formation of a chimeric mRNA transcript. We describe a patient with acute myelogenous leukemia (M1), with del(16)(q22), who expressed the chimeric transcript. Reverse transcriptase polymerase chain reaction and the sequencing of its product showed fusion of 5'CBFB at position 495 to 3'MYH11 at position 1201. To our knowledge, this is the first report of an AML (M1) case with del(16) and CBFB/MYH11 rearrangement.
Amino Acid Sequence↗
[Adult T-cell leukemia with diffuse panbronchiolitis-like lung infiltration].
A 46-year old man was admitted complaining of dyspnea. Physical examination revealed superficial lymph nodes swelling, and coarse crackles over the lung. Chest X-ray film showed diffuse small granular shadows, suggesting diffuse panbronchiolitis (DPB). Peripheral blood smears showed cells with flower like nuclei. HTLV-I antibody was positive in the serum. He was diagnosed as having adult T-cell leukemia (ATL). Transbronchial lung biopsy showed diffuse infiltration of mononuclear cells around bronchioalveoli. The mononuclear cells stained positively for Pan T, CD2, CD3, CD4, CD5, CD25, and DNA from the cells showed HTLV-I provirus monoclonal integration. This is a rare case of ATL accompanied by DPB-like bronchioalveolar ATL cell infiltration.
Antigens, CD↗