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Biomedical subjects

H Shiku

Publications and source records attributed to H Shiku.

At least 91 records · Page 5Linked to original sources
PubMed1999

Low BCL-2 expression in acute leukemia with t(8;21) chromosomal abnormality.

In de novo t(8;21) AML which shows terminal neutrophilic differentiation, the BCL-2 expression was found to be significantly lower than that in types of other AML regardless of the phenotypic differentiation status. An inverse correlation between BCL-2 expression and the S/G2/M population cells was observed in AML. The S/G2/M population in t(8;21)AML was larger than in the other types of AML. In t(8;21)AML, spontaneous apoptosis after a 12-h liquid culture was prominent, and the autonomous DNA synthesis after a 72-h liquid culture was low. G-CSF and IL-5 promoted the colony formation of t(8;21)AML cells. The data suggest that, in vivo, the low BCL-2 in t(8;21)AML induced entry of cells from the G0/G1 phase to S phase, but the cells easily die by apoptosis, in vitro. The low BCL-2 expression and the supportive effects of G-CSF and IL-5 in t(8;21)AML is thought to be a key phenomenon which might be related to the formation of the in vivo blood picture, such as prominent neutrophilic differentiation and eosinophilia. Cellular extracts from t(8;21)AML cell line Kasumi-1 bound to both the AML1 and CRE binding sites in the bcl-2 promoter, but none of the cellular extracts from de novo t(8;21)AML bound to either of these sites. The DNA binding activity of transactivators in de novo t(8;21)AML is different from that in Kasumi-1 cells probably due to the phosphorylation status.

Acute Disease↗
PubMed1999

Expressions of four major protein Ser/Thr phosphatases in human primary leukemic cells.

Activity and expression of four major protein serine/threonine (Ser/Thr) phosphatases, protein phosphatase type 1 (PP1), protein phosphatase type 2A (PP2A), protein phosphatase type 2B (PP2B) and protein phosphatase type 2C (PP2C) were evaluated in normal peripheral leukocytes, and in various leukemic cells from patients with acute myelogenous leukemia (AML), common acute lymphocytic leukemia (cALL), or chronic lymphocytic leukemia (CLL). PP1 was the most abundant phosphatase in blood cells, and relative abundance of each phosphatase was: PP1 > PP2A > PP2B approximately = PP2C. PP1 activity and its expressions were higher in blasts of AML-M4 and -M5 than in cells of AML-M1, cALL and CLL. PP2A activity and its expression were higher in blasts of AML-M3, -M4 and -M5 than in cells of AML-M1, cALL and CLL. Activity and expression of both PP1 and PP2A in normal monocytes were highest, and PP2A activity in normal neutrophils was lowest among normal leukocytes. PP2B activity and its expression were higher in blasts of AML-M2, -M3 and normal lymphocytes. PP2C activity and its expression were relatively constant in various leukemic cell types. Activities of PP1 and PP2A of AML blasts correlated positively with the expression of CD11b, whereas activities of PP1 and PP2B correlated negatively with the expression of CD7. Thus, each phosphatase was ubiquitously but differently expressed in various leukemic cell types and in normal leukocytes. These data also suggest that expressions of PP1, PP2A and PP2B are relatively low in leukemic blasts arresting at the stage of early pluripotent stem cells, and are differently modulated during the course of myelomonocytic commitment and maturation.

Acute Disease↗
PubMed1999

Survival of human leukaemic B-cell precursors is supported by stromal cells and cytokines: association with the expression of bcl-2 protein.

We searched for cytokines with the potential to support the survival of human B-cell precursor acute lymphoblastic leukaemia (pre-B ALL) cells. 47 patients with pre-B ALL were classified into four stages: stage I, CD19+CD10-CD20-; stage II, CD19+CD10+CD20-; stage III, CD19+CD10+CD20+cytoplasmic mu-heavy chain (cmu)-; stage IV, CD19+CD10+CD20+cmu. Interleukin (IL)-3 receptor alpha chain (IL-3Ralpha) was expressed in all stages, whereas the expressions of IL-7Ralpha and IL-2Ralpha were pronounced in stages IV and II, respectively. Neither IL-3, IL-7 nor IL-2 supported the survival of pre-B ALL cells. When pre-B ALL cells were layered on stromal, MS-10, cells, viability of the pre-B ALL cells increased. Addition of IL-3 to culture containing MS-10 cells enhanced the survival of pre-B ALL cells in all cases, whereas addition of IL-7 augmented the survival of pre-B ALL cells of some cases of stage III and all cases of stage IV. The survival of pre-B ALL cells was also supported by the conditioned media of MS-10 cells. Stromal-cell-derived factor 1 (SDF-1) supported the survival of pre-B ALL cells. Effects of the conditioned media of MS-10 cells were abrogated by an anti-SDF-1 neutralizing antibody. The extent of survival of pre-B ALL cells supported by stromal cells and IL-3 and IL-7, correlated with the expression level of bcl-2 protein. The effects of stromal cells may be in part related to SDF-1.

Adult↗
PubMed1999

Myeloid differentiation antigen and cytokine receptor expression on acute myelocytic leukaemia cells with t(16;21)(p11;q22): frequent expression of CD56 and interleukin-2 receptor alpha chain.

We report the cellular characteristics of cells from three patients with de novo acute myelocytic leukaemia (AML) with t(16;21)(p11;q22), two M4 and one M5a according to the FAB classification, and two permanent cell lines with t(16;21)(p11;q22), TSU1621MT and YNH-1. The FUS/ERG fusion mRNA was demonstrated in all cases by reverse transcriptase-polymerase chain reaction (RT-PCR). The immunophenotypes of the AML cells, and YNH-1 and TSU1621MT cell lines with t(16;21) were characterized as CD34+CD33+CD13+CD11b+CD18+CD56+ HLA-DR-/+. Cells from all samples strongly expressed c-kit, granulocyte colony-stimulating factor receptor (G-CSFR), c-fms (macrophage colony-stimulating factor receptor), interleukin-3 receptor alpha chain (IL-3Ralpha), and granulocyte macrophage colony-stimulating factor receptor alpha chain (GM-CSFRalpha), and these data corresponded well to the growth responsiveness to the cytokines. IL-2Ralpha expression was also found in all t(16;21) samples, but IL-2 did not act on the proliferation of the leukaemic cells in in vitro cultures. G-CSF distinctly promoted the proliferation of leukaemic cells of t(16;21) AML, but did not enhance the expression of MPO and neutrophil differentiation of these cells. Our findings indicate that AML cells with t(16;21) preserve stem cell properties such as CD34 and c-kit expression, and suggest that they have the potential to differentiate into a monocytic lineage. The relationship between the unique cellular characteristics (especially CD56 and IL-2Ralpha expression) and FUS/ERG protein remains undetermined.

Adolescent↗
PubMed1999

De novo CD5-positive diffuse large B-cell lymphoma: clinical characteristics and therapeutic outcome.

To determine the clinical significance of CD5 expression in diffuse large B-cell lymphoma (DLBL) without a clinical history of low-grade B-cell lymphoma, we have reviewed the clinical features and therapeutic outcome of 25 patients with de novo CD5-positive DLBL, and compared the results with those of 87 patients with CD5-negative DLBL and 22 patients with mantle cell lymphoma (MCL). The patients with de novo CD5-positive DLBL had clinical characteristics of elderly onset (median age 63, range 37-91), and female predominance (male/female 10/15). 21 (84%) of these patients had extranodal involvement at presentation, with great variation in the sites. In comparison with the patients with CD5-negative DLBL, the treatment outcome for the patients with de novo CD5-positive DLBL was very poor with frequent relapse. The failure-free survival curve was almost identical to that of patients with MCL, showing that standard chemotherapy for DLBL was not effective for most of the patients with de novo CD5-positive DLBL. These findings suggest that de novo CD5-positive DLBL forms a distinct subgroup of DLBL.

Adult↗
PubMed1999

Hemostatic markers in Japanese patients undergoing anticoagulant therapy under thrombo-test monitoring.

The objective of this study was to evaluate several molecular markers of hemostasis in 84 patients with hypercoagulable state, treated with warfarin under thrombo-test (TT) monitoring; TT was expressed as percent of control (TT%). In all patients, the average values of international normalized ratio (INR) of prothrombin time (PT;PT-INR) was 1.68+/-0.49; this increase in PT-INR was not, however, significant in patients under TT% monitoring. There were no thrombotic or severe bleeding complications in these patients during a period of 2 years. Plasma levels of thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex (PPIC), D-dimer, and soluble fibrin monomer (sFM) were slightly increased, suggesting that anticoagulant therapy was not completely effective in our Japanese patients based on the values of TT%. Activated partial thromboplastin time, PT-INR, TT% and protein C activity were significantly correlated with the dose of warfarin; fibrinogen, activated thromboplastin, TAT, PPIC, D-dimer, sFM, protein S and thrombomodulin were not significantly correlated with the dose of warfarin. The PT-INR was negatively correlated with TT%, protein C and protein S, and the correlation between PT-INR and TT-INR was better than that between PT-INR and TT%. The range of TT% was not correlated with the plasma levels of TAT, PPIC, D-dimer or sFM, but the range of PT-INR was correlated with the plasma level of TAT, D-dimer and sFM. The percentage of TAT, D-dimer and sFM within normal range was significantly low in patients with high PT-INR. These finding showed that PT-INR is better than TT% for monitoring the anticoagulant therapy with warfarin, and that TT should be expressed as INR. The values of PT-INR should be more than 1.7 during the anticoagulant therapy with warfarin in Japanese patients with high risk of thrombosis.

Adult↗
PubMed1999

Expression of DCC protein in colorectal tumors and its relationship to tumor progression and metastasis.

A loss of heterozygosity (LOH) at the DCC gene locus was detected in colorectal tumors, and this LOH might be related to metastasis. The aim of this study was to determine DCC protein expression in colorectal cancer and to evaluate its prognostic value. Allelic loss of the DCC locus was observed in 16 of the 23 patients (66.7%). In all 16 patients with LOH, DCC expression was decreased in the cancer tissue compared with the adjacent normal mucosa. All 23 colorectal tumors had decreased expression of this protein relative to the adjacent normal colonic mucosa in Western blot analysis. The levels of DCC protein were significantly lower in cancer tissues than in adenoma tissues. Decreased DCC protein expression was also observed by immunohistochemistry in the colorectal cancer cases. There were significant correlations between DCC protein expression and histologic type, venous invasion, and hematogenous metastasis. Patients with DCC-protein-negative tumors had a greater relative risk of recurrence compared with those whose tumors were DCC protein-positive. The 5-year survival rate was 91.0% in patients with DCC-protein-positive tumors, and 58.8% in those with DCC-protein-negative tumors; these differences between the two groups of patients were significant (p < 0.01). In multivariate analysis using the Cox regression model, DCC protein expression emerged as an independent prognostic indicator. These findings suggested that a decrease in DCC expression may have an important role in the progression of colorectal cancers and may be a biologic marker of prognostic significance.

Adenoma↗
PubMed1999

Aberrations of the tissue factor pathway in patients positive for lupus anticoagulant.

To evaluate the relationship between the tissue factor (TF) pathway and lupus anticoagulant (LA), in the present study, we measured the plasma levels of TF antigen and TF pathway inhibitor (TFPI) antigen in patients positive for LA. Plasma TF and TFPI levels in LA-positive patients were significantly higher than levels in healthy volunteers (p < 0.01). In LA-positive patients, there were no significant differences in plasma TF and TFPI levels between patients with and without thrombosis. In patients with thrombosis, there was no significant difference in the plasma TF level between LA-positive and LA-negative patients; however, the plasma TFPI level in LA-positive patients was significantly lower than that in LA-negative patients (p < 0.01). We also examined the TF pathway in human umbilical venous endothelial cells (HUVEC) incubated with plasma of LA-positive patients, LA-negative patients, and healthy volunteers. TF activity was significantly higher (p < .05) in HUVECs incubated with the plasma of LA-positive patients than in cells incubated with the plasma of the other two groups (p < .01). However, there was no significant difference in TFPI antigen levels among the media of HUVECs incubated with the plasma of all groups. The viability of HUVEC incubated with the plasma of LA-positive patients with thromboses, LA-positive patients without thromboses, and LA-negative patients with thromboses were significantly lower than that of HUVECs incubated with the plasma of healthy volunteers (p < .01). These findings suggest that abnormalities of the TF pathway plays an important role in the mechanism of hypercoagulability in LA-positive patients. LA may affect vascular endothelial cells causing thrombogenesis.

Adult↗
PubMed1999

Outcome of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome in Japan.

We examined 159 patients with thrombotic thrombocytopenic purpura and hemolytic uremic syndrome in Japan. The subjects were divided in three groups; 90 patients with thrombotic thrombocytopenic purpura, 51 patients with verotoxin-induced hemolytic uremic syndrome, and 18 patients with drug-induced hemolytic uremic syndrome. Eighty-two percent of the patients with thrombotic thrombocytopenic purpura had associated neurological disorders and 78% of drug-induced hemolytic uremic syndrome associated with pulmonary edema. Renal insufficiency was noted in the 69% cases with both hemolytic uremic syndrome groups. Seventeen patients with thrombotic thrombocytopenic purpura had systemic lupus erythematosus and 6 were pregnant. Autoantibody were positive in 53% of thrombotic thrombocytopenic purpura. Seventy-seven percent of patients with thrombotic thrombocytopenic purpura received plasma exchange at 4,000 mL/day three times a week, 71% antithrombotic agents, and 78% steroid administration, respectively. However, 27% of the patients with hemolytic uremic syndrome were treated by hemodialysis in addition to antithrombotic agents. When drug-induced hemolytic uremic syndrome was diagnosed, the drug was immediately discontinued and the patients were treated with antiplatelet agents. Seventy-four percent of the patients with thrombotic thrombocytopenic purpura were alive at 26 weeks compared with 95% of those with hemolytic uremic syndrome. As thrombotic thrombocytopenic purpura had a high mortality rate in Japan, we should carry out early diagnosis and early treatment.

Adolescent↗
PubMed1999

Increased activated protein C: protein C inhibitor complex and decreased protein C inhibitor levels in patients with chronic renal failure on maintenance hemodialysis.

Hemostatic abnormalities were examined in 55 patients during maintenance hemodialysis (HD). Before HD, plasma protein C and protein S antigens were almost within the normal range, while plasma thrombin-antithrombin III complex (TAT III) and plasmin-plasmin inhibitor complex (PPIC) levels in HD patients were increased slightly, and plasminogen activator inhibitor 1 level was significantly increased, compared to that in normal volunteers. Plasma activated protein C (APC) and protein C inhibitor (PCI) complex and APC alpha 1 antitrypsin (alpha 1AT) complex were not detected in normal volunteers; however, plasma APC-PCI complex was increased in 36 of the patients and plasma APC-alpha 1AT complex was increased in 25 patients. Plasma PCI levels in these patients before HD were significantly decreased. Plasma TAT, PPIC, and tissue type plasminogen activator levels were significantly higher before HD than after 1 hour HD and at the end of HD, while the changes in plasma protein C antigen, protein S antigen, PCI antigen, APC-PCI complex, and APC-alpha 1AT complex were not significant after 1 hour of HD or at the end of HD compared to levels before HD. Plasma PCI levels were correlated with APC-PCI complex, suggesting that decreased PCI levels might be caused by the activation of protein C.

Adult↗
PubMed1999

Distinctive actions of interleukin-13 and interleukin-4 on growth of hematopoietic progenitors.

We examined the effects of interleukin (IL)-13 and IL-4 on growth of hematopoietic progenitors from 5-fluorouracil (5-FU)-treated mice, using an in vitro culture system. IL-13 or IL-4 alone failed to support colony formation by enriched marrow cells. IL-4 but not IL-13 in combination with IL-11 yielded a significant number of colonies. Neither IL-4 nor IL-13 affected colony formation supported by IL-3. When tested with two-factor combinations, IL-4 but not IL-13 suppressed the formation of colonies including multilineage colonies in the absence of IL-11. The inhibitory effects of IL-4 were not lineage-specific. Delayed addition experiments demonstrated that IL-4 is inhibitory in the early stage of colony formation. Effects of IL-4 on colony formation by pooled blast cells derived from 5-day culture of post-5-FU marrow cells was not evident. These findings indicate that IL-4 but not IL-13 is a negative regulator of hematopoietic progenitors, suggesting distinctive roles for IL-4 and IL-13 in early hematopoiesis.

Animals↗
PubMed1999

Bone marrow-derived dendritic cells incorporate and process hydrophobized polysaccharide/oncoprotein complex as antigen presenting cells.

We have previously shown that a novel hydrophobized polysaccharide/oncoprotein complex vaccine can induce immune responses against the HER2/neu/c-erbB2 (HER2) expressing tumors. Bone marrow-derived dendritic cells (DCs), as antigen presenting cells (APCs), are the first candidates for presentation of tumor antigens. The aim of this study was to see whether DCs are able to elicit antigen specific host immune responses by stimulating the proliferation of T cells after exposure to cholesteryl group bearing pullulan (CHP) and HER2 protein complex. Vaccination by CHP-HER2 complex was as effective as cholesteryl group bearing mannan (CHM) and HER2 complex on which we reported previously. Immunization of mice with HER2 expressing CMS17HE tumor cells generated both CD4+ T cells and CD8+ T cells reactive with CHP-HER2 complex pretreated DCs. In addition, immunization with either CHP-HER2 complex or HER2 protein alone could also generate both CD4+ T cells and CD8+ T cells specifically reactive with CHP-HER2 complex pretreated DCs. The complete rejection of tumors occurred when immunization with CHP-HER2 complex pretreated DCs was started 10 days after tumor inoculation. Therefore, bone marrow-derived DCs pretreated with hydrophobized polysaccharide/oncoprotein complex are a powerful tool for enhancing the effectiveness of oncoprotein for anti-tumor vaccination, opening new options for immune cell therapy.

Animals↗
PubMed1999

HUB1 is an autoantigen frequently eliciting humoral immune response in patients with adult T cell leukemia.

The immunological screening of a cDNA phage expression library prepared from an adult T cell leukemia (ATL) cell line, ST1, was performed with IgG class antibodies in the serum of an ATL patient by the SEREX method to analyze the repertoire of antigen molecules in ATL. Ten different cDNAs, 7 previously reported and 3 newly identified, were isolated. One of the identified cDNAs was homologous to the recently reported gene, HTLV-I U5RE binding protein 1 (HUB1) encoding a protein binding to a possible repressor element of the long terminal repeat of the human T lymphotropic virus type I (HTLV-I). The obtained cDNA was expressed as a fusion protein with glutathione S-transferase. HUB1 protein was prepared by subsequent treatment of the fusion protein with thrombin. Reactivity of IgG serum samples from ATL patients, asymptomatic HTLV-I carriers and normal donors against the purified protein was examined by Western blot analysis. Twenty-one out of 30 samples (70.0%) from ATL patients, 10/24 samples (41.7%) from HTLV-I carriers and 9/24 samples (37.5%) from healthy donors showed positive reactivity, indicating the autoantigenicity of HUB1. The development of ATL may be related to higher production of antibodies against HUB1.

Adult↗
PubMed1999

Retroviruses prepared from human DAF expressing murine packaging cells acquire resistance against human serum.

The complement system of the human body inactivates the infectious ability of retroviruses injected as an artificial gene transfer vector. We established new murine leukemia virus (MuLV) packaging cell lines; D2SS and D7S which express decay-accelerating factor (DAF) on their surface. Both D2SS and D7S were resistant against incubation with fresh human serum. Moreover, the retroviruses produced from these packaging cell lines were also resistant to serum treatment. This resistance can be inhibited by DAF neutralizing antibody 1C6. These data demostrate that DAF induces a partial protection of MuLV infection from the human complement system.

3T3 Cells↗
PubMed1999

gamma delta T-cell lymphoma: a clinicopathologic study of 6 cases including extrahepatosplenic type.

We report 6 cases of gamma delta T-cell lymphoma (GDTL) among 115 peripheral T-cell lymphomas over a 12-year period. All patients exhibited extranodal lymphomas, comprising 3 hepatosplenic, 1 cutaneous, 1 intestinal, and 1 thyroidal lymphoma. Despite therapies, all but 1 patient died of disease within 16 months of diagnosis. The cytologic features of lymphoma cells in 4 of 5 cases examined were very similar: coarsely reticulated nuclear chromatin, multiple small nucleoli, abundant faintly eosinophilic granular cytoplasm, and focal angiocentric proliferation. All 6 lymphomas showed Cd3+CD4-CD8-/+ phenotype. CD56 was positive in 3 cases, 1 of which was also CD16 positive. Perforin and T-cell intracellular antigen-1 were positive in all 5 cases examined. Southern blot analysis revealed clonal gene rearrangements of the T-cell receptor delta-chain gene in all 5 cases examined. Based on these findings, together with a review of the literature, GDTLs seem to have several common lineage-specific features, although clinical presentation and course of GDTL are heterogeneous.

Adolescent↗
PubMed1999

A case of T-lineage lymphoblastic lymphoma/leukemia with t(4;11)(q21;p15) that switched to myelomonocytic leukemia at relapse.

A 51-year-old Japanese woman, initially diagnosed with T-lineage (CD2+, CD7+, CD3-, CD4-, CD8-) lymphoblastic lymphoma with t(4;11)(q21;p15), relapsed with acute myelomonocytic leukemia with the identical chromosomal abnormality. Southern-blot analysis revealed clonal rearrangements of an immunoglobulin heavy chain gene (JH) and T-cell receptor genes (J delta 1, J gamma 1, C beta 1) at first presentation, but germ line configurations of these genes at relapse. Leukemias with t(4;11)(q21;p15) may involve a hematopoietic progenitor capable of multilineage differentiation.

CD3 Complex↗