Search PubMed⌕ Search

Biomedical subjects

H Shiku

Publications and source records attributed to H Shiku.

At least 37 records · Page 2Linked to original sources
PubMed2001

Successful autologous peripheral blood stem cell transplantation for relapsed intravascular lymphomatosis.

We describe a case of relapsed intravascular lymphomatosis (IVL) successfully treated with autologous PBSCT. A 59-year-old Japanese female patient with IVL who had achieved CR after six courses of biweekly CHOP therapy developed lymphoma. She achieved a second CR after six courses of modified biweekly CHOP therapy, followed by autologous PBSCH and high-dose chemotherapy (CBDCA, VP-16, MCNU, CY) with PBSCT. There has not been any evidence of recurrence 48 months after PBSCT. Our case suggests that PBSC is acceptable as a source for stem cell rescue in IVL.

Antigens, CD34↗
PubMed2001

Aggressive neoplastic plasma cell growth with MLL gene rearrangement after high-dose therapy with autologous stem cell support for multiple myeloma.

We report a case of a patient with IgA kappa multiple myeloma (MM) mobilized with etoposide and subsequently receiving high-dose melphalan (HDM) with stem cell support. She relapsed rapidly post transplantation. Southern blot and fluorescent in situ hybridization analysis showed MLL gene rearrangement in the myeloma cells, which was not detected in the sample at diagnosis or in the PBSC harvested with etoposide plus G-CSF. These observations suggest that clonal rearrangement of the MLL gene is caused by etoposide. Patients with MM undergoing HDM with stem cell rescue may be at an increased risk of not only secondary leukemia, but also secondary genetic abnormalities in myeloma cells, especially those receiving priming with etoposide for peripheral blood stem cell collection.

Antineoplastic Agents, Phytogenic↗
PubMed2001

Efficient ex vivo generation of dendritic cells from CD14+ blood monocytes in the presence of human serum albumin for use in clinical vaccine trials.

Dendritic cells (DC) with the potential to induce anti-tumour immunity represent one of the promising candidates for cancer vaccines. Efficiency of ex vivo DC generation depends on culture conditions, especially protein components in the plasma or serum used. Using human serum albumin (HSA), we devised a constant and reproducible culture method for DC generation from peripheral blood CD14+ cells. The number of DC obtained with 2% HSA-supplemented cultures containing granulocyte-macrophage colony-stimulating factor and interleukin 4 were consistently higher than in cultures with various concentrations of autologous plasma or serum. The concentrations and time points tested for plasma or serum considerably affected the number of DC recovered. DC prepared with HSA acquired the ability to uptake dextran, and expressed high levels of major histocompatibility (MHC) and co-stimulatory molecules similar to DC cultured with autologous plasma or serum. Although DC cultured with autologous plasma or serum consisted of CD1a+ and CD1a- populations, DC differentiated in the presence of HSA expressed CD1a. DC obtained with HSA primed and induced immunogenic peptide-specific cytotoxic T lymphocytes against a tumour rejection antigen, HER2. These findings suggest that our method for preparation of DC with HSA should prove valuable in DC generation for immunotherapy.

Cancer Vaccines↗
PubMed2001

Inhibition by combined therapy with ticlopidine and aspirin of enhanced platelet aggregation during physical exercise in patients with coronary artery disease.

BACKGROUND: Strenuous exercise can be a major trigger for coronary thrombosis and it enhances platelet aggregation. METHODS: We evaluated the effect of antiplatelet therapy on shear stress-induced platelet aggregation (SIPA), in addition to agonist-induced aggregation, before and immediately after ergometer exercise in patients with stable coronary artery diseases (CAD). Forty-eight patients with stable CAD were randomly distributed into 3 groups: no antiplatelet drug (patient control, n = 16), aspirin (ASA) monotherapy (n = 16), and combined therapy with ticlopidine (TIC) and ASA (n = 16). RESULTS: There were significant increases in not only adenosine phosphate (ADP)- and collagen-induced platelet aggregation but also in SIPA during exercise by the patient control group. ASA monotherapy did not attenuate the enhanced ADP-induced aggregation nor SIPA. Combined ASA + TIC therapy significantly inhibited SIPA as well as ADP-induced aggregation both before and after exercise. Significant increases in levels of plasma von Willebrand factor (vWF) occurred during exercise, and these antiplatelet therapies had no apparent effect on increased vWF levels during exercise. Exercise induced a significant increase in the plasma thrombin-antithrombin III complex level with no significant changes in the level of plasmin-plasmin inhibitor complex level in all 3 groups. CONCLUSIONS: Combined therapy with ASA + TIC effectively inhibited increased platelet aggregability in response to acute exercise, with no effects on coagulant or fibrinolytic potentials in patients with CAD. The data suggest that TIC combined with ASA may be superior to ASA alone in preventing acute coronary events during exercise in patients with coronary atherosclerotic disease.

Adenine Nucleotides↗
PubMed2001

Endosonographic images of low-grade lymphoma of mucosa-associated lymphoid tissue after radiotherapy.

Recently, radiation therapy has been reported to be effective in patients with low-grade lymphoma of mucosa-associated lymphoid tissue (MALT) of the stomach. We describe changes in endoscopic ultrasonographic (EUS) findings after radiation therapy in a patient with low-grade gastric MALT lymphoma. Endoscopic ultrasonography initially showed enlargement of regional lymph nodes and diffuse thickening of the second and third mural layers in the gastric body. Two months after the end of radiation therapy, EUS showed hypoechoic changes in the third layer that corresponded to the ulcer scar but no wall thickening or lymph node enlargement. The hypoechoic changes were thought to reflect inflammatory change. We conclude that EUS is useful for assessing the response to radiation therapy in patients with low-grade gastric MALT lymphoma.

Aged↗
PubMed2001

Increased plasma thrombomodulin as a vascular endothelial cell marker in patients with thrombotic thrombocytopenic purpura and hemolytic uremic syndrome.

Several hemostatic and vascular endothelial cell markers were measured in 39 patients with thrombotic thrombocytopenic purpura (TTP)/hemolytic uremic syndrome (HUS) and in 20 healthy volunteers to examine the relationship between the occurrence of hemostatic abnormality or vascular endothelial cell injury and patient outcome. The plasma levels of von Willebrand factor, tissue plasminogen activator (TPA), plasminogen activator inhibitor (PAI-1), and the TPA-PAI-1 complex were significantly increased in TTP/HUS patients; however, the levels of these markers were not significantly different between TTP/HUS patients who survived and those who died, suggesting that these markers might not be directly related to outcome. The plasma levels of soluble granule membrane protein (GMP)-140 were significantly higher in TTP/HUS patients than in healthy volunteers, suggesting that platelets and vascular endothelial cells are activated or injured in TTP/HUS. There was no significant difference in GMP-140 levels between TTP/HUS patients with good and poor prognoses; this may be owing to the release of GMP-140 from platelets. The plasma thrombomodulin (TM) levels in TTP/HUS patients were significantly higher than in healthy volunteers; the plasma TM levels were significantly higher in patients who died than in patients who survived. These findings showed that TM levels reflect the outcome and that the outcome of TTP/HUS depends on the presence vascular endothelial cell injury. The plasma protein C and antithrombin levels were markedly reduced in TTP/HUS patients who died compared with those who survived. These findings suggest that reduced plasma antithrombin and protein C may be useful markers of systemic vascular endothelial injury. In conclusion, the results of this study showed that the outcome of TTP/HUS is related to vascular endothelial cell injury and that plasma TM, antithrombin, and protein C levels may be useful markers of systemic vascular endothelial cell injury.

Adolescent↗
PubMed2001

Plasma levels of total plasminogen activator inhibitor-I (PAI-I) and tPA/PAI-1 complex in patients with disseminated intravascular coagulation and thrombotic thrombocytopenic purpura.

In this study, we examined changes in the plasma levels of total plasminogen activator inhibitor-I (PAI-I) and tissue-type plasminogen activator (tPA)/PAI-I complex in patients with disseminated intravascular coagulation (DIC) and in those with thrombotic thrombocytopenic purpura (TTP) to investigate the fibrinolytic function and its relation to organ failure. The plasma levels of total PAI-1 and tPA/PAI-I complex were significantly higher in patients with DIC, pre-DIC, and TTP than in those with non-DIC. The plasma levels of thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex (PPIC), D-dimer, thrombomodulin (TM), total PAI-I, and tPA/PAI-I complex were significantly higher in patients with organ failure than in those without organ failure. The plasma levels of total PAI-I and tPA/PAI-I complex were markedly increased in patients with acute leukemia. The plasma levels of total PAI-I, but not those of tPA/PAI-I complex, were significantly increased in patients with sepsis or with solid cancer. In all cases, total PAI-I or tPA/PAI-I complex was not significantly correlated with any hemostatic marker. Measurement of total PAI-I and tPA/PAI-I complex may be useful in the diagnosis of DIC.

Antifibrinolytic Agents↗
PubMed2001

Clinical significance of low protein phosphatase-1 activity of blasts in acute myelogenous leukemia with high white cell counts.

We have previously shown that protein phosphatase-1 (PP1) is the most abundant Ser/Thr phosphatase in human adult primary leukemic cells. To determine the clinical importance of PP1 expression, we compared PP1 activity of leukemic blasts with other putative prognostic factors in 46 patients with acute myelogenous leukemia (AML) who were treated with remission induction chemotherapy. PP1 was ubiquitously but differently expressed in various FAB subtypes (M1-M5), although PP1 activity was significantly higher in blasts of AML-M4 than in AML-M2. PP1 activity was significantly lower in elderly patients > or =55 years (P=0.005), and in those with high white cell counts > or =100,000/microl (P=0.039) at initial diagnosis. Correlation was observed between PP1 activity (<0.15 vs > or =0.15 nmol/min/10(8) cells) and prognosis of AML patients. Eleven of 46 patients with less than 0.15 nmol/min/10(8) cells (low PP1 activity group) had significantly lower overall survival than those with > or =0.15 nmol/min/10(8) cells (high PP1 activity group). The median overall survival was 8 months for patients with low PP1 activity compared to 27 months for those with high PP1 activity in their AML cells. Multivariate analysis using Cox's proportional hazard model showed that low PP1 activity significantly contributed to prognosis. This preliminary study suggests that low PP1 activity may be associated with shortened survival time for AML patients with high white cell counts.

Antigens, CD34↗
PubMed2001

Expression pattern of hybrid phenotype in adult acute lymphoblastic leukemia.

We examined the expression of hybrid phenotype in 236 adults with acute lymphoblastic leukemia (ALL; 188 B-lineage ALL and 48 T-lineage ALL). In B-lineage ALL, myeloid antigen (mAg) CD15 was concentrated in CD10-CD20- cases (49%); CD13 (42%); and CD33 (43%) in CD10+CD20- cases. This trend had no correlation with the presence of Ph1 or t(4;11) chromosomal abnormality. T-cell antigen CD2, CD4, and CD7 was seen in four, four, and two cases, respectively, and CD4+ and CD7+ cases commonly expressed CD13 and/or CD33 (CD13/CD33). In T-lineage ALL, expression of mAg, CD11b (47%), CD13 (38%), CD15 (28%), and CD33 (51%) was restricted to CD3- cases. B-cell antigen CD19 was found in two cases with CD7 solely as T-cell antigen, and these cases possessed CD13/CD33. CD21 was detected in three cases with CD3. In whole ALL, CD13/CD33 was associated closely with the presence of stem-cell antigen CD34, and in T-lineage ALL, CD13/CD33 had a significant correlation with additional stem-cell features, such as HLA-DR, multidrug resistance 1 (MDR1) and c-kit gene expression. Our results suggest that immature ALL cells frequently express B+M+, T+M+, and occasionally B+T+M+ phenotype; that B+T+M- phenotype is extremely rare; and that mAg expression in B-lineage ALL is complicated as compared to T-lineage ALL.

Adolescent↗
PubMed2001

[Plasma levels of soluble fibrin in patients with disseminated intravascular coagulation].

Soluble fibrin(SF) is formed in the early-activated state of blood coagulation and quantitative measurement of SF shows high potential as a parameter for the diagnosis of suspected disseminated intravascular coagulation(DIC). The aim of the present study is to evaluate the usefulness of a newly developed SF test utilizing SF specific monoclonal antibody(F405). Among hemopoietic and non-hemopoietic tumor patients, 249 patients with suspected DIC were collected. The SF level showed a good correlation with the DIC score and the SF levels in DIC patients were significantly higher than those in s-DIC and pre-DIC patients. Receiver operating characteristic(ROC) analysis also showed that the specificity and sensitivity of the SF assay were higher than those of thrombin-antithrombin complex(TAT). In conclusion, these results indicate that the SF assay is a highly precise method for the diagnosis and screening of DIC stages.

Disseminated Intravascular Coagulation↗
PubMed2001

Comparison of the responses of global tests of coagulation with molecular markers of neutrophil, endothelial, and hemostatic system perturbation in the baboon model of E. colisepsis--toward a distinction between uncompensated overt DIC and compensated non-overt DIC.

This study correlates changes in neutrophilic activity and endothelial injury with markers of hemostatic activity following the infusion of increasing concentrations of E. coli organisms. It focuses on the hemostatic response as a marker of microvascular injury and uses the response to increasing concentrations of E. coli to refine our definition of disseminated intravascular coagulation (DIC) and distinguish between a compensated (non-overt DIC) and uncompensated (overt DIC) response. We observed that the global coagulation tests reflected activation of the hemostatic system in a dose dependent manner (overt DIC) in the early phases (T+2 to 6 h) of the response to increasing concentrations of E. coli, but that they failed to do so in the late phases (T+ 24 to 48 h). We observed that molecular markers, soluble thrombomodulin and elastase, unlike thrombin/antithrombin and plasmin/antiplasmin complexes, remained elevated out to T+24 to 48 h indicating endothelial injury that persists beyond the initial inflammatory insult in compensated as well as uncompensated DIC.

Animals↗
PubMed2000

A HER2/NEU-derived peptide, a K(d)-restricted murine tumor rejection antigen, induces HER2-specific HLA-A2402-restricted CD8(+) cytotoxic T lymphocytes.

We have identified an H-2K(d)-binding peptide, HER2p780 (PYVSRLLGI), derived from murine HER2/neu (HER2), that can induce HER2-specific murine cytotoxic T lymphocytes (CTL). Weekly vaccination of BALB/c mice by syngeneic dendritic cells pulsed with HER2p780 peptide, entirely common to murine and human HER2, suppressed growth of pretransplanted HER2-expressing syngeneic tumors. A HER2-expressing human cancer cell line SKOV3 transfected with murine H-2K(d) cDNA could also be lysed by HER2p780-specific murine CTLs, indicating that human HER2-expressing cancer cells can process and present the cognate peptide in the context of H-2K(d). Since H-2K(d) and HLA-A2402 molecules have similar anchor motifs, the possibility of inducing HER2-specific CTL activity with HER2p780 in HLA-A2402 individuals was examined. CD8(+) CTL clones specific for HER2-expressing cancer cell lines were established from peripheral blood lymphocytes with HLA-A2402 by repeatedly sensitizing with peptide-pulsed autologous dendritic cells as well as peripheral blood mononuclear cells. Detailed analysis of their specificity revealed that the cytotoxicity of CTL clones is specific for the cognate peptide with HLA-A2402 restriction. The results suggest that HER2p780 is a unique peptide that may function as a tumor rejection antigen peptide in HLA-A2402 individuals, as it was directly proven here to function in a murine tumor system.

Animals↗
PubMed2000

Increased platelet aggregability in response to shear stress in acute myocardial infarction and its inhibition by combined therapy with aspirin and cilostazol after coronary intervention.

Although antiplatelet therapy with a specific inhibitor of phosphodiesterase-3 cilostazol improves stent patency compared with use of aspirin (ASA) alone, the specific role of cilostazol on platelet aggregation in patients with acute myocardial infarction (AMI) is less well understood. Thirty-six patients with AMI who were successfully treated with primary angioplasty were randomized to 3 antiplatelet regimens: ASA alone (n = 12), ASA + ticlopidine (n = 12), and ASA + cilostazol (n = 12). We measured shear stress-induced platelet aggregation (SIPA) using a modified cone-plate viscometer on admission and on day 7, and evaluated the inhibitory effects of combination therapy with ASA + cilostazol on SIPA. Compared with cases of stable coronary artery disease, significant increases in SIPA and plasma von Willebrand factor activity were observed in patients with AMI before they received antiplatelet therapy. On day 7 after primary angioplasty, ASA did not inhibit SIPA (65 +/- 15% vs 57 +/- 11%, p = 0.086), whereas both combination therapies of ASA + ticlopidine and ASA + cilostazol significantly inhibited SIPA in patients with AMI (ASA + ticlopidine: 61 +/- 15% vs 45 +/- 13%, p <0. 0001; ASA + cilostazol: 64 +/- 14% vs 43 +/- 9%, p <0.005). There was a significant correlation of SIPA with adenosine diphosphate (ADP)-induced platelet aggregation (r = 0.412, p = 0.003) and with plasma von Willebrand factor activity (r = 0.461, p = 0.0008). These data suggest that patients with AMI have increased platelet aggregability in response to high shear stress. Combined antiplatelet therapy with ASA + cilostazol appears to be as effective as therapy with ASA + ticlopidine for reducing SIPA in patients with AMI who are undergoing primary angioplasty.

Aged↗
PubMed2000

HTLV-1 unrelated adult T-cell leukemia/lymphoma with unique phenotype and karyotype.

We describe a unique case of adult T-cell leukemia/lymphoma (ATL). The patient had typical clinicohematological features as ATL, but showed a lack of antibody to human T-cell leukemia virus type-1 (HTLV-1) and was negative for HTLV-1 proviral DNA in the peripheral mononuclear cells by means of polymerase chain reaction. The phenotype of tumor cells revealed CD7+, CD5+, CD2+, CD3+, WT31-, TcR delta 1-, CD4-, CD8-, CD25-, and the karyotype showed a 5q-, t(12;18). HTLV-1 unrelated ATL is very rare, and the karyotype as in our case has not been reported previously.

Aged↗
PubMed2000

Decreased tissue factor and tissue-plasminogen activator antigen in relapsed acute promyelocytic leukemia.

This study evaluated hemostatic data in 28 patients with newly diagnosed acute promyelocytic leukemia (APL) and 15 patients with relapsed APL. Activated partial thromboplastin time and prothrombin time were prolonged at initial onset of APL. Plasma level of fibrinogen was significantly decreased in patients with initial disease of APL, but it was not decreased significantly during the relapse of APL. Plasma fibrin and fibrinogen degradation products levels were significantly increased and platelet counts significantly decreased in both groups. Plasma levels of antiplasmin significantly decreased at initial onset but not during relapse. Plasma levels of antithrombin were within normal range in patients with initial disease but significantly decreased in those with relapse. Plasma levels of D-dimer, soluble fibrin monomer (sFM), plasmin-plasmin inhibitor complex (PPIC), and thrombin antithrombin complex (TAT) levels were significantly high in both groups. Plasma levels of PPIC, sFM, and D-dimer were significantly higher at initial onset of APL than during relapse. However, there was no significant difference in DIC score between patients with initial onset and those with relapse; plasma levels of tissue factor (TF) significantly increased in both groups, but they were significantly higher at initial onset of APL than during relapse. TF and tissue type plasminogen activator (t-PA) antigen levels in leukemic cell lysate were significantly increased in both groups, and they were significantly lower during relapse than at initial onset. Hemostatic abnormalities occurring in patients with relapsed APL might be the result of the decrease of TF and t-PA in leukemic cells. These findings suggest that DIC in APL patients with relapse might not be caused only by TF and t-PA and thus should be treated with different therapy from patients with initial onset of APL.

Adolescent↗
PubMed2000

Plasma levels of activated protein C-protein C inhibitor complex in patients with hypercoagulable states.

Plasma levels of activated protein C (APC)-protein C inhibitor (PCI) were significantly increased in patients with disseminated intravascular coagulation (DIC), thrombotic thrombocytopenic purpura (TTP), acute myocardial infarction (AMI), pulmonary embolism (PE), or deep vein thrombosis (DVT) and in patients undergoing hemodialysis (HD). Plasma levels of APC-alpha(1)-antitrypsin (AT) complex were significantly increased in patients with DIC and in those with TTP. Plasma levels of PCI were significantly decreased in patients with DIC, non-DIC, or TTP and in those undergoing HD. In the pre-DIC stage, the plasma levels of APC-PCI complex were significantly increased but not those of APC-alpha(1)-AT complex. These data suggest that measurements of APC-PCI complex and APC-alpha(1)-AT complex may be useful for the diagnosis of DIC. After treatment of DIC, the plasma levels of APC-PCI complex and APC-alpha(1)-AT complex were significantly decreased, but not those of PCI. Plasma levels of thrombin-antithrombin complex (TAT), plasmin-alpha(2)-plasmin complex (PPIC), D-dimer, and soluble fibrin monomer (SFM) were markedly increased in patients with DIC or pre-DIC and were moderately increased in patients with non-DIC, TTP, AMI, PE, or DVT and in those undergoing HD. The receiving operating characteristic (ROC) analysis showed that SFM and the APC-PCT complex are useful markers for diagnosis of DIC. The specificity of plasma TAT and PPIC levels was low. The positive rate of APC-PCI complex was higher than 90% with DIC, TTP, AMI, PE, and it was higher than 60% with DVT and HD. Since the APC-PCI complex was elevated not only in patients with venous thrombosis but also in those with arterial thrombosis, components of the protein C pathway might be useful markers for the diagnosis of arterial thrombosis.

Antithrombin III↗
PubMed2000

Increased plasma levels of tissue factor pathway inhibitor-activated factor X complex in patients with disseminated intravascular coagulation.

Plasma levels of tissue factor pathway inhibitor (TFPI)-activated factor Xa (FXa) complex were measured in patients with disseminated intravascular coagulation (DIC), pre-DIC, and DIC. Plasma levels of plasmin-plasmin inhibitor complex (PPIC), D-dimer, and soluble fibrin monomer (SFM) were significantly higher in patients with DIC than in those with pre-DIC or non-DIC; the levels of these hemostatic markers were significantly higher in patients with pre-DIC than in those with non-DIC. Plasma levels of thrombin-antithrombin complex (TAT) were significantly higher in patients with DIC or pre-DIC than in those with non-DIC. Plasma levels of tissue factor (TF), total TFPI, free TFPI, and TFPI-Xa complex were significantly higher in patients with DIC than in those with non-DIC. Plasma levels of TFPI-Xa complex were significantly increased in patients with pre-DIC as compared to those with non-DIC; however, plasma free TFPI levels were significantly decreased in patients with pre-DIC as compared to those with non-DIC. These findings suggest that free TFPI might be consumed in the pre-DIC state, thereby confirming the activation of the extrinsic pathway. Plasma levels of TFPI-Xa complex were significantly correlated with TF, free TFPI, and total TFPI. Increased plasma TFPI-Xa complex levels might be useful for the diagnosis of DIC or pre-DIC, particularly that occurring by activation of the extrinsic pathway of blood coagulation.

Anticoagulants↗