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Biomedical subjects

K Usuki

Publications and source records attributed to K Usuki.

At least 37 records · Page 2Linked to original sources

[Polyclonal plasmacytosis in peripheral blood and leukocytoclastic vasculitis in Castleman's disease].

A 62 year-old man had fever, splenomegaly, systemic lymphadenopathy and palpable petechiae. Laboratory studies showed leukocytosis (10,200/microliters) with plasma cells (23%) and polyclonal gammopathy. Southern blot analysis of peripheral blood mononuclear cells showed no rearrangement of immunoglobulin genes, indicating polyclonal plasmacytosis in peripheral blood. A diagnosis of Castleman's disease was made by the cervical lymph node biopsy, which showed onion-skin structures in the germinal centers and plasmacytosis in the interfollicular region. A skin biopsy of the purpura lesion disclosed leukocytoclastic vasculitis. This is an unusual case of Castleman's disease presenting plasmacytosis in peripheral blood and leukocytoclastic vasculitis.

Castleman Disease↗

[Mediastinal germ-cell tumor associated with AML (M7)--the syndrome of mediastinal germ-cell tumors associated with hematologic neoplasia?].

In October 1992, a 36-year-old man was diagnosed as having mediastinum mixed germ cell tumor (stage II), and was treated with surgical operation and combination chemotherapy including VP16 (total VP16 dose; 1,500 mg/m2). After that, remission had been sustained, but leukocytosis (15,700/microliter) with 37% of peroxidase-negative blasts and thrombocytopenia developed in September, 1995. Bone marrow showed remarkable reticulin fibrosis and increase of atypical immature cells that were immunophenotypically factor VIII+/CD42+/CD61+. Thus, we diagnosed acute megakaryoblastic leukemia (M7). Based on no abnormality of chromosome 11q23 and no rearrangements of MLL gene, we diagnosed the syndrome of mediastinal germ-cell tumors associated with hematologic neoplasia. Furthermore, the neuron-specific enolase level was elevated (95.9 ng/ml). Soon after complete remission was reached by combination chemotherapy, the leukemia was relapsed, and the he died 3 months after the onset of leukemia. To our knowledge, this is the third case report of this syndrome in Japan and the first one of leukemia with high level of serum neuron-specific enolase.

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↗

Steatocystoma multiplex: a case with unusual clinical and histological manifestation.

A 35-year-old man at our clinic was found to have steatocystoma multiplex manifested by dome-shaped nodules confined to the scalp and forehead. One of four cyst biopsy specimens revealed large lining cells with granular cytoplasm adjacent to typical steatocystoma epithelial lining cells. Neither fibrosis nor inflammatory changes were noted in the surrounding connective tissue. The large granular lining cells had immunohistochemical characteristics of the macrophage/monocyte lineage. This case appears to be an unusual clinical and histological manifestation of steatocystoma multiplex.

Adult↗

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↗

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↗

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↗

A case of chromomycosis with tumor-like growth.

A 66-year-old woman who lived on Tokunoshima Island, a small and remote southern island of the Japanese archipelago, had suffered from chromomycosis for more than 30 years and presented with a tumor-like growth on the posterior crural region of his right leg. Fonsecaea pedrosoi was identified as the pathogen from its growth pattern and micromorphological characteristics. The patient was successfully treated with 5-fluorocytosine, itoraconazole, and topical thermotherapy.

Administration, Topical↗

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↗