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S Fukuhara

Publications and source records attributed to S Fukuhara.

At least 73 records · Page 4Linked to original sources
PubMed2000

Whole blood prothrombin time using diluted tissue factor is shortened in spontaneous hypertensive rats.

Clinical screening tests for blood coagulation that use plasma as samples cannot estimate the participation of platelets, leukocytes, and erythrocytes in blood coagulation system. We developed an assay to evaluate the total coagulation ability of blood and whole blood prothrombin time (WPT) using the principle of prothrombin time with the diluted-tissue factor as a trigger and a newly developed apparatus, STA, viscosity change detection system (electromagnetic clot detection). The activation of platelets by Ca ionophore shortened WPT and increased the expression of CD62P on the platelet surface. WPTs in citrated blood of spontaneous hypertensive rats (SHR) were significantly shorter than those of controls, Wistar Kyoto rats (WKY). Plasma levels of thrombin-antithrombin III (TAT) in SHR were significantly higher than those of WKY. Moreover, WPT and TAT levels were significantly correlated. Based on these results, WPT was found to be useful to estimate the activation of blood coagulation in whole blood.

Animals↗
PubMed2000

Alternating combination chemotherapy C-MOPP (cyclophosphamide, vincristine, procarbazine, prednisone) and ABVd (adriamycin, bleomycin, vinblastine, dacarbazine) in clinical stage II-IV Hodgkin's disease: a multicenter phase II study (JCOG 8905). The Lymphoma Study Group of the Japan Clinical Oncology Group.

BACKGROUND: The main form of cytotoxic treatment for advanced Hodgkin's disease (HD) is conventional dose multiagents chemotherapy. As HD is not common in Japan, we conducted a phase II study of the commonly used combination chemotherapy (CCT) regimen established in the West for Japanese patients with advanced HD to confirm the efficacy and safety. METHOD: Between October 1989 and February 1993, a multicenter phase II study of alternating CCT C-MOPP (cyclophosphamide, vincristine, procarbazine, prednisone) and ABVd (adriamycin, vinblastine, bleomycin, dacarbazine) to evaluate its clinical usefulness for clinical stage (cS) II-IV HD was conducted by the Lymphoma Study Group of the Japan Clinical Oncology Group. RESULTS: Seventy-nine previously untreated patients were enrolled in the study. For 67 eligible patients, the response rate was 92.5% with 83.6% complete response (CR). For 40 cS II and 27 cS III/IV patients the response rate was 95.0% with 90.0% CR and 88.9% with 74.1% CR, respectively. The overall 5-year survival rate was 84.8%. Those of cS II and cS III/IV were 92.5 and 73.1%, respectively. There was no significant difference between cS II and cS III/IV (p = 0.1025). The progression-free 4-year survival rate was 72.8%. Those of cS II and cS III/IV were 77.5 and 65.7%, respectively. There was no significant difference between cS II and cS III/IV (p = 0.2483). Grade 4 toxicity by the criteria of the World Health Organization consisted of leukocytopenia in 28.4% of patients. There was GPT elevation in 4.5%, nausea/vomiting in 11.9% and CNS in 1.5% of patients, but there was no treatment-related death. CONCLUSION: The C-MOPP/ABVd regimen for Japanese patients with advanced HD is considered to be one of the effective CCTs according to the results of the present phase II study.

Adolescent↗
PubMed2000

Double involvement of extramammary Paget's disease in the genitalia and axilla.

We here reported a case of an 82-year-old man with double involvement of extramammary Paget's disease in the genitalia and axilla. Physical examination revealed erythema and reddish tumors on the pubic area and scrotum and irregular-shaped erythema on the left axilla. The skin biopsy sample from the genital area showed Paget's cells in the epidermis and upper dermis. The specimen from the left axilla showed Paget's cells scattered in the epidermis but not in the dermis.

Aged↗
PubMed2000

Thrombopoietin levels in patients undergoing autologous peripheral blood stem cell transplantation.

BACKGROUND AND OBJECTIVES: High-dose chemotherapy with peripheral blood stem cell transplantation (PBSCT) has become an important treatment for hematological and solid tumors. Several reports on endogeneous production of thrombopoietin (TPO) in patients undergoing intensive chemotherapy have been published. We measured TPO levels in patients undergoing autologous PBSCT in order to elucidate the role of TPO in megakaryopoiesis and platelet recovery following stem cell transplantation. We also examined whether PBSC from different patient groups (patients with lung cancer and malignant lymphoma) had different effects on TPO levels. MATERIALS AND METHODS: Serum levels of TPO and other cytokines were determined by ELISA before and after PBSCT in 10 patients with lung cancer and 18 patients with malignant lymphoma. RESULTS: Compared to platelet counts at 1 week after transplantation, those at 3 weeks were significantly increased (p<0.001). In contrast, serum TPO levels were significantly decreased 3 weeks after PBSCT (p<0.01). There were no significant differences in levels of other cytokines between 1 and 3 weeks after transplantation. A strong correlation was found between serum TPO levels and circulating platelet counts (r = -0. 675; p<0.0001). Platelet counts exhibited a significant recovery and TPO levels also decreased significantly in malignant lymphoma patients after transplantation. There were no significant differences in TPO levels in lung cancer patients, although the same tendencies as for malignant lymphoma patients were observed for both platelet count and TPO level. On analysis of transfused PBSC, we found that the numbers of CFU-GM were similar in lung cancer and malignant lymphoma patients. However, the numbers of CD34+ cells were significantly higher in lung cancer patients than in malignant lymphoma patients. CONCLUSION: Our findings suggest that TPO plays a critical role in the reconstitution of megakaryopoiesis and platelet production following PBSCT, and that the type of stem cell, tumor, and preceding chemotherapy affect serum TPO levels after transplantation.

Adult↗
PubMed2000

Vitamin-D receptor genotype and renal disorder in Japanese patients with systemic lupus erythematosus.

BACKGROUND/AIMS: It is known that allelic variants of the gene encoding the vitamin-D receptor (VDR) detected by BsmI increase the risk of some advanced malignant tumors, suggesting that such variants may cause functional differences in 1,25(OH)(2) vitamin D(3). We examined the VDR genes of Japanese systemic lupus erythematosus (SLE) patients, to determine whether different genotypes are correlated with SLE or its criteria. METHODS: VDR genotyping of 58 unrelated Japanese SLE patients was performed based on polymerase chain reaction-restriction fragment length polymorphism (RFLP). Following amplification, products were digested with BsmI. The RFLPs were coded as Bb, where the uppercase letter signifies the absence of the digested site and the lowercase letter signifies the presence of the site. RESULTS: The frequency of the VDR BB genotype was significantly higher in SLE patients (15.5%, n = 9/58, p < 0.0001) than in controls (5.7%, n = 5/87). Furthermore, a larger proportion of bb individuals was observed among patients with nephrotic syndrome (61.5%, n = 8/13) than among SLE patients without renal dysfunction (35.7%, n = 10/28). There was a significant tendency for the population of patients with the bb genotype to be correlated with that of patients with renal dysfunction (p = 0.0304). CONCLUSION: These findings suggest that the BB genotype might trigger the development of SLE, and that the bb genotype is associated with lupus nephritis.

Adult↗
PubMed2000

Effect of sarpogrelate hydrochloride on platelet-derived microparticles and various soluble adhesion molecules in diabetes mellitus.

We measured platelet-derived microparticles, activated platelets, and various adhesion molecules in 48 patients with diabetes mellitus. We also performed a comparative study of these parameters before and after administration of sarpogrelate hydrochloride. The numbers of platelet-derived microparticles and activated platelets were increased significantly in diabetic patients, and CD63-positive platelets were increased in patients with diabetic complications and poorly controlled blood glucose. Soluble adhesion molecules and thrombomodulin were also increased significantly. After administration of sarpogrelate hydrochloride, not only CD62p- and CD63-positive platelets, but also platelet-derived microparticles were decreased significantly. Soluble adhesion molecules and thrombomodulin were also significantly decreased after the treatment. These data suggest that (a) in patients with diabetes, antiplatelet therapy with sarpogrelate hydrochloride is a useful antithrombin therapy because it suppresses the production of intrinsic coagulants by activated platelets; and (b) sarpogrelate hydrochloride decreases endothelial cell damage via adhesion molecules.

Antigens, CD↗
PubMed2000

Platelets expressing P-selectin and platelet-derived microparticles in stored platelet concentrates bind to PSGL-1 on filtrated leukocytes.

The levels of interleukin-6 and platelet-derived microparticles (PMPs) were measured in the blood of 137 patients with side effects from platelet concentrate (PC) transfusion with leukocyte removal filtration, P-selectin-expressing platelet and PMPs in stored PC before and after the filtration, and filtered leukocytes positive for P-selectin glycoprotein ligand-1. The side effects, which were observed in 203 transfusions for 84 patients with hematologic disease and 53 patients with nonhematologic disease with no significant difference between the two groups, included urticaria (75.9%), erythema (18.7%), and fever (17.2%), but no anaphylactic reactions. The levels of interleukin-6 and PMP correlated in both groups, and were significantly higher in the hematologic disease group than in the nonhematologic disease group. The level of PMP, but not interleukin-6, was significantly higher for patients testing positive for allergic reaction than for those testing negative. In the stored PC prior to filtration, the level of interleukin-6 was normal. The level of P-selectin-expressing platelets and PMPs was elevated before filtration, but was significantly lower after filtration. Taken together, the results suggest that PMP is involved in the generation of transfusion reactions, and indicate that both platelets and PMP displaying P-selectin bind to P-selectin glycoprotein ligand-1 of leukocytes retained by the leukocyte filter.

Blood Platelets↗
PubMed2000

Molecular and clinical features of non-Burkitt's, diffuse large-cell lymphoma of B-cell type associated with the c-MYC/immunoglobulin heavy-chain fusion gene.

PURPOSE: t(8;14)(q24;q32) and/or c-MYC/immunoglobulin heavy-chain (IGH) fusion gene have been observed not only in Burkitt's lymphoma (BL) but also in a proportion of non-BL, diffuse large-cell lymphoma of B-cell type (DLCL). We explored molecular features of DLCL with c-MYC/IGH fusion and the impact of this genetic abnormality on clinical outcome of DLCL. PATIENTS AND METHODS: A total of 203 cases of non-BL DLCL were studied. Genomic DNA extracted from tumor tissues was subjected to long-distance polymerase chain reaction (LD-PCR) using oligonucleotide primers for exon 2 of c-MYC and for the four constant region genes of IGH. RESULTS: Twelve cases (5.9%) showed positive amplification; one had a c-MYC/Cmicro, nine had a c-MYC/Cgamma, and two had a c-MYC/Calpha fusion sequence. Restriction and sequence analysis of the LD-PCR products, ranging from 2.3 to 9.4 kb in size, showed that breakage in the 12 cases occurred within a 1.5-kb region that included exon 1 of c-MYC in combination with breakpoints at the switch regions of IGH (10 of 12). In 10 cases, Myc protein encoded by the fusion genes demonstrated mutations and/or deletions. Six cases had additional molecular lesions in BCL-2 or BCL-6 and/or p53 genes. The age range of the 12 patients was 44 to 86 years, with a median age of 65.5 years. Five patients had stage I/II disease, and seven had stage III/IV disease. Lactate dehydrogenase was elevated in nine of 11 subjects. Seven showed involvement of the gastrointestinal tract. All patients were treated by surgery and/or chemoradiotherapy; six died of the disease within 1 year, resulting in the poorest 1- and 2-year survival rates among DLCL subgroups. CONCLUSION: The c-MYC/IGH fusion gene of DLCL is identical to that of the sporadic type of BL (sBL). DLCL with c-MYC/IGH shares clinical features with sBL but is characterized further by an older age distribution.

Adult↗
PubMed2000

[Bone marrow transplantation-associated thrombotic microangiopathy manifested by visual disturbance].

In October 1996, a 26-year-old woman was given a diagnosis of acute myeloblastic leukemia, FAB subtype M1. Treatment with combined chemotherapy achieved a complete remission (CR). In May 1997, the patient received an allogenic bone marrow transplant (BMT) from an HLA-identical sibling donor. Cyclosporine (CsA) and short-term methotrexate were given for graft-versus-host disease (GVHD) prophylaxis. Successful engraftment was obtained and signs of acute or chronic GVHD never developed. Five months after BMT, the patient experienced low-grade fever and blurred vision. Retinal examination demonstrated intraretinal hemorrhages, cotton-wool spots, and retinal detachments, which were presumably attributable to multiple thrombosis of retinal microvessels. The patient also exhibited hemolytic anemia with red cell fragmentation, thrombocytopenia, elevated lactate dehydrogenase, and renal impairment, and was thus given a diagnosis of BMT-associated thrombotic microangiopathy (BMT-TM). Discontinuation of CsA and administration of ticlopidine and prednisolone induced successful recovery from BMT-TM. Three months after the onset of BMT-TM, however, the patient experienced generalized clonic-tonic seizures with consciousness loss. Single-photon-emission computed tomography revealed blood-flow disturbances in the brain, suggesting the recurrence of microthrombosis. Accordingly, multiple transfusions of fresh frozen plasma were administered together with dipyridamole and aspirin. The patient gradually recovered and remained asymptomatic through the following 13 months. Currently, early diagnosis of BMT-TM is considered to be difficult. We suggest that careful examination of the ocular base may be useful for the early detection of BMT-TM.

Adult↗
PubMed2000

Adult T-cell leukemia successfully treated with allogeneic bone marrow transplantation.

Adult T-cell leukemia (ATL) is associated with human T-cell leukemia virus type 1 (HTLV-1) and is known to be a refractory disease of highly poor prognosis. We describe a case of ATL treated with allogeneic bone marrow transplantation (allo-BMT). The allo-BMT successfully induced complete remission in the patient. Currently, at 24 months post BMT, there has been no evidence of minimal residual disease (MRD) detected by polymerase chain reaction (PCR) assay for the T-cell receptor gamma chain gene. By contrast, PCR analysis demonstrated the reappearance of the cells harboring the integrations of the HTLV-1 proviral DNA 9 months after the BMT. These findings may imply a reversion to the carrier state rather than the recurrence of the leukemia from the MRD. The clinical consequence of our case illustrates that allo-BMT is an effective therapy, at least for achieving longer disease-free survival in ATL.

Bone Marrow Transplantation↗
PubMed2000

[Antithymocyte globulin treatment in 11 patients with aplastic anemia].

We report the response to, and toxicity of antithymocyte globulin (ATG) treatment in 11 consecutive patients (7 men and 4 women; median age 46 years) with aplastic anemia (AA). Six of the patients had severe disease and 5 had moderate disease; all were treated within one year from diagnosis. The ATG regimen was the initial treatment for 6 patients, but a sequential treatment for the other 5. Cyclosporin A was administered orally 1-3 weeks after the ATG treatment. All patients were assessed for over 6 months (median, 20.4 months); 8 showed a good response, 1 a minimal response, and 2 no response. Disease severity had no influence on the response. In 1 patient, ATG treatment had to be discontinued because of hepatic toxicity. However, adverse reactions were not severe in the other 10 patients. These findings suggest that ATG treatment is a safe and effective therapy for AA.

Adult↗
PubMed2000

[Rapid development of multiple meniscal signs complicating invasive pulmonary aspergillosis in a patient receiving chemotherapy for acute leukemia].

This report describes the rapid development of multiple meniscal signs complicating invasive pulmonary aspergillosis in a 53-year-old man receiving chemotherapy for acute leukemia. While undergoing first induction therapy for AML, he developed chest pain, and multiple bilateral infiltrations were seen in chest roentgenograms. Administration of antibiotics, antifungal agents, steroid pulse therapy and G-CSF was begun. Pulmonary cavities with meniscal signs developed. The next day, pneumothorax and hemothorax were noted. Although drainage and mechanical ventilation were performed, the patient died after massive hemoptysis. Invasive pulmonary aspergillosis was diagnosed at autopsy.

Aspergillosis↗
PubMed2000

[A patient with hemorrhage originating from an unknown coagulation pathway inhibitor].

The hemorrhagic disorders associated with circulating anticoagulant are rare but well known as the disease derived from inhibitors(alloantibody or autoantibody), which arise against specific coagulation factors. We encountered a patient with hemorrhage at the lower limbs originating from an unknown coagulation pathway inhibitor. Activated partial thromboplastin time(APTT) prolonged and cross mixing test indicated a coagulation pathway inhibitor. Levels of coagulation factors VIII, IX, XI, and XII were extremely low. Predonine therapy was effective to stop the hemorrhage. To clarify the inhibitor, we treated the patient's plasma with protein A Sepharose, and the factor VIII activity was recovered to a normal level after passing through the column. Gel filtration of the patient's plasma and protein A Sepharose adsorbed fraction of the patient's plasma with Superdex 200 revealed that the inhibitor activity against blood coagulation eluted at the position of IgG, which was detected by the prolongation of APTT of normal pooled plasma. These data indicated that the inhibitor was IgG and its inhibitory spectrum was non-specific and broad. The results of laboratory tests and the clinical features in our patient were similar to those in a previous study by Dahlback(Blood 62, 218-225, 1983). The hemorrhagic abnormality of that patient was derived from the autoantibody to phospholipid, which inhibits the activation of prothrombin. An investigation into the effect of anti-phospholipid antibody in our patient is currently being performed in our laboratory.

Adult↗
PubMed1999

Health-related quality of life among renal-transplant recipients in Japan.

BACKGROUND: This study had four goals: (1) to evaluate an index of health-related quality of life (HQOL) among renal-transplant recipients in Japan, (2) to compare HQOL of renal-transplant recipients with that of the Japanese population as a whole, and (3,4) to study associations of HQOL with renal function and with the time since transplantation. METHODS: Questionnaires were distributed to 570 subjects. All were outpatients, were 16 years old or older, and were studied at least 1 year after they had received their latest renal transplant. HQOL was assessed with the Short Form 36-item health survey. Subjects' physicians provided data on renal function. Associations of HQOL with serum creatinine concentration and with the time since transplantation were evaluated by logistic regression. RESULTS: The response rate was 83%. Data from patients with diabetes and from those who had had at least two renal transplants were excluded; data from 395 recipients were analyzed. On the physical functioning, general health perception, vitality, and social functioning scales, the patients' scores were significantly lower than the Japanese national-norm scores. General health perception was particularly low. Serum creatinine concentrations were associated with general health perception, vitality, and social functioning. Longer times since transplantation were associated with better social functioning. CONCLUSIONS: Although social and physical functioning may improve after transplant surgery, a low self-rating of general health seemed to remain. The rarity of renal transplantation in Japan and other psychosocial factors may explain the low self-rating of general health in Japanese renal-transplant recipients.

Adolescent↗
PubMed1999

Divergent signaling pathways link focal adhesion kinase to mitogen-activated protein kinase cascades. Evidence for a role of paxillin in c-Jun NH(2)-terminal kinase activation.

Stimulation of a number of cell surface receptors, including integrins and G protein-coupled receptors, results in the activation of a non-receptor tyrosine kinase known as focal adhesion kinase (FAK). In turn, this kinase is believed to play a critical role in signaling to intracellular kinase cascades controlling gene expression such as extracellular signal-regulated kinases (ERKs), by a yet poorly defined mechanism. Furthermore, whether this tyrosine kinase also mediates the activation of other mitogen-activated protein kinase family members, such as c-Jun NH(2)-terminal kinases (JNKs), is still unclear. We show here that the activation of FAK by anchoring to the cell membrane is itself sufficient to stimulate potently both ERK and JNK. These effects were found to be phosphatidylinositol 3-kinase-independent, as FAK effectively stimulated Akt, and wortmannin suppressed Akt but not ERK or JNK activation. As previously reported by others, activation of ERK correlated with the ability of FAK to induce tyrosine phosphorylation of Shc. Surprisingly, however, stimulation of JNK was not dependent on the kinase activity of FAK or on the ability to induce tyrosine phosphorylation of FAK substrates. Instead, we provide evidence that FAK may stimulate JNK through a novel pathway involving the recruitment of paxillin to the plasma membrane and the subsequent activation of a biochemical route dependent on small GTP-binding proteins of the Rho family.

Anisomycin↗
PubMed1999

Relationship between platelet activation and cytokines in systemic inflammatory response syndrome patients with hematological malignancies.

We investigated the significance of platelet activation and platelet-derived microparticles (PMP) in 14 patients with systemic inflammatory response syndrome (SIRS) and hematological malignancies. In the phenotypic analysis of lymphocytes, there was a significant decrease of total and activated T cells after panipenem/betamipron (PAPM/BP) treatment (p<0.05). The percentages of helper/inducer T cells and suppressor/cytotoxic T cells were insignificantly decreased after PAPM/BP treatment. The number of natural killer (NK) cells of potent activity was significantly decreased after treatment (p<0.05). The levels of the cytokines interleukin (IL)-1beta, IL-6, and IL-8 in the patients were increased before treatment. IL-1beta concentrations were not changed after treatment. In contrast, the IL-6 and IL-8 levels were significantly decreased (p<0.05) after treatment, while tumor necrosis factor (TNF)-alpha and interferon gamma remained almost normal. We found an increase of soluble IL-2 receptor (sIL-2R) and soluble vascular cell adhesion molecule-1 (sVCAM-1) levels in the patients before treatment. After treatment, the sIL-2R concentrations tended to be decreased and sVCAM-1 levels showed a significant decrease (p<0.01). In contrast, soluble thrombomodulin (sTM) level did not change. Regarding the platelet activation markers, CD62P, CD63, and PMP levels in the patients were increased before treatment. CD62P and CD63 tended to be decreased after treatment, whereas PMP levels were significantly reduced from 1,056+/-103 to 762+/-64/10(4) platelets (p<0.05). Furthermore, CD62P, CD63, and PMP correlated with the levels of IL-6 and IL-8. These results suggest that activated platelets and PMP may be predictive markers in pre-disseminated intravascular coagulation and hypercytokine conditions related to SIRS.

Adult↗
PubMed1999

A CD1a+/CD11c+ subset of human blood dendritic cells is a direct precursor of Langerhans cells.

Based on the relative expression of CD11c and CD1a, we have identified three fractions of dendritic cells (DCs) in human peripheral blood, including a direct precursor of Langerhans cells (LCs). The first two fractions were CD11c+ DCs, comprised of a major CD1a+/CD11c+ population (fraction 1), and a minor CD1a-/CD11c+ component (fraction 2). Both CD11c+ fractions displayed a monocyte-like morphology, endocytosed FITC-dextran, expressed CD45RO and myeloid markers such as CD13 and CD33, and possessed the receptor for GM-CSF. The third fraction was comprised of CD1a-/CD11c- DCs (fraction 3) and resembled plasmacytoid T cells. These did not uptake FITC-dextran, were negative for myeloid markers (CD13/CD33), and expressed CD45RA and a high level of IL-3Ralpha, but not GM-CSF receptors. After culture with IL-3, fraction 3 acquired the characteristics of mature DCs; however, the expression of CD62L (lymph node-homing molecules) remained unchanged, indicating that fraction 3 can be a precursor pool for previously described plasmacytoid T cells in lymphoid organs. Strikingly, the CD1a+/CD11c+ DCs (fraction 1) quickly acquired LC characteristics when cultured in the presence of GM-CSF + IL-4 + TGF-beta1. Thus, E-cadherin, Langerin, and Lag Ag were expressed within 1 day of culture, and typical Birbeck granules were observed. In contrast, neither CD1a-/CD11c+ (fraction 2) nor CD1a-/CD11c- (fraction 3) cells had the capacity to differentiate into LCs. Furthermore, CD14+ monocytes only expressed E-cadherin, but lacked the other LC markers after culture in these cytokines. Therefore, CD1a+/CD11c+ DCs are the direct precursors of LCs in peripheral blood.

Antigens, CD1↗