Biomedical subjects

Y Niho

Publications and source records attributed to Y Niho.

At least 163 records · Page 9Linked to original sources

PubMed1997

Pericentric inversion of chromosome 16 and eosinophilia in chronic myelomonocytic leukemia.

We report a case of myelodysplastic syndrome with bone marrow eosinophilia and the chromosomal abnormality, inv(16)(p13q22). Hematologic findings including monocytosis and trilineage myelodysplasia were consistent with chronic myelomonocytic leukemia, and numerous abnormal eosinophils were present in the bone marrow. Chromosomal analysis of all metaphase cells from peripheral blood and bone marrow revealed in(16)(p13q22), which is well known characteristic of acute myelomonocytic leukemia with eosinophilia (M4Eo). Both monocytes and eosinophils in this case may be derived from common leukemic progenitors affected by inv(16)(p13q22).

Aged↗

PubMed1997

Granulocyte colony-stimulating factor-combined marrow-ablative chemotherapy and autologous blood cell transplantation for the treatment of patients with acute myelogenous leukemia in first remission. The Fukouka Bone Marrow Transplant Group.

We conducted a clinical trial to increase the chemosensitivity of residual leukemic cells by combining G-CSF to marrow-ablative chemotherapy, including cytosine arabinoside (Ara-C), and facilitated by autologous blood cell transplantation (ABCT) for treatment of acute myelogenous leukemia (AML) in first complete remission. A total of 16 patients were consecutively treated with granulocyte colony-stimulating factor (G-CSF)-combined high-dose chemotherapy (busulfan, etoposide and Ara-C) followed by autotransplantation of peripheral blood progenitor cells, which had been collected after the consolidation chemotherapy. At a median follow-up time of 44.5 months, the probability of 5-year event-free survival was 74.5% with only three leukemic relapses. This preliminary observation suggests the effectiveness of G-CSF-combined conditioning and ABCT as a post-remission therapy for AML.

Adolescent↗

PubMed1997

Interleukin-10 inhibits the autocrine growth of leukemic blast cells from patients with acute myeloblastic leukemia.

The effect of interleukin-10 (IL-10) on the growth of leukemic blast cells from patients with acute myeloblastic leukemia (AML) is in need of clarification. We therefore examined the effect of IL-10 on AML cells obtained from 10 patients. Although granulocyte colony-stimulating factor (G-CSF) and/or granulocyte/macrophage colony-stimulating factor (GM-CSF) was able to stimulate the growth of AML progenitor cells to form leukemic blast colonies, IL-10 itself demonstrated no leukemic blast colony-forming activity and no synergistic stimulating activity with other cytokines. However, leukemic blast colonies were formed without the addition of exogenous cytokines in four cases and IL-10 suppressed these spontaneous colony formations in two of the four cases. Since the production of G-CSF and GM-CSF was observed in these two cases, the presence of an autocrine growth mechanism mediated by these cytokines was suggested. When serial concentrations of IL-10 were added, the production of G-CSF and GM-CSF was dramatically inhibited in a dose-dependent manner. These findings suggested that IL-10 could suppress the autocrine growth of AML cells by inhibiting their production of G-CSF and/or GM-CSF. In addition, the administration of IL-10 may be harmless to normal hematopoiesis because IL-10 did not suppress the growth of normal hematopoietic progenitor cells. Our study provides experimental support for the clinical application of IL-10 in patients with AML.

Autocrine Communication↗

PubMed1997

Increased incidence of cytomegalovirus (CMV) infection and CMV-associated disease after allogeneic bone marrow transplantation from unrelated donors. The Fukuoka Bone Marrow Transplantation Group.

Cytomegalovirus (CMV) infection and CMV-associated disease were monitored using the CMV antigenemia assay in 72 patients who received allogeneic bone marrow transplantation (BMT), and their incidences were compared between related and unrelated donor transplant patients. The incidence of CMV infection after BMT was significantly higher in patients who received transplants from HLA-matched unrelated donors than from HLA-matched sibling donors (87% vs 53%, P < 0.05). CMV-associated disease developed in 73% of unrelated and in 14% of sibling donor transplant patients (P < 0.01). The peak levels of CMV antigenemia were significantly higher in unrelated donors than in sibling donor transplant patients (16 vs 1 CMV antigen-positive cells per 50000 WBCs, P < 0.01). The median number of CMV antigen-positive cells on first detection was also significantly higher in unrelated donor transplant patients (15 vs 1, P < 0.01). The detection of CMV antigen-positive cells preceded the development of CMV-associated disease in 18% of unrelated donor transplant patients, suggesting a lower predictive value of CMV antigenemia for subsequent CMV-associated disease in unrelated donor BMT. Careful monitoring and further studies are needed for the early diagnosis and prevention of CMV-associated disease in unrelated donor BMT.

Adolescent↗

PubMed1997

The effects of a simplified method for cryopreservation and thawing procedures on peripheral blood stem cells.

A simplified method for cryopreservation at -80 degrees C of peripheral blood stem cells (PBSC) has been increasingly used for autologous PBSC transplantation in Japan. Although this method, using 6% hydroxyethyl starch (HES) and 5% dimethyl sulfoxide (DMSO) as a cryoprotectant without rate-controlled freezing, has several advantages over the conventional method using 10% DMSO with rate-controlled freezing, little is known about effects of long-term cryopreservation for years and thawing process on hematopoietic progenitors. We examined the recovery rates of BFU-E and CFU-GM in sample tubes cryopreserved by the simplified method under various conditions as follows: (1) long-term storage for 1-5 years; (2) DMSO exposure for 1 h after rapid thawing; and (3) thawing at a lower temperature other than 37 degrees C. In our study, we found that the recovery rates of BFU-E and CFU-GM were not affected by the length of cryopreservation period; they remained at more than 70% on average for 16-61 months. In our hands, a 1-h exposure to DMSO after rapid thawing was not toxic for hematopoietic progenitors. Furthermore, there was no significant difference in the recovery rates of BFU-E and CFU-GM between thawing at 37 degrees C and 20 degrees C. These observations indicate that PBSC cryopreserved for at least 5 years by the simplified method can be used clinically without losing hematopoietic activity, and suggest that hematopoietic activity of the thawed PBSC may be unaffected when PBSC are infused slowly within 60 min or even when PBSC are thawed gradually at room temperature.

Blood Preservation↗

PubMed1997

Autologous peripheral blood stem cell transplantation for acute myelogenous leukemia.

The safety and efficacy of myeloablative therapy followed by autologous peripheral blood stem cell transplantation (ABSCT) for acute myelogenous leukemia (AML) were evaluated in 60 patients. Peripheral blood stem cells (PBSC) were collected during recovery after consolidation chemotherapy. High-dose chemotherapy consisting of busulfan (16 mg/kg), etoposide (40 mg/kg), and cytosine arabinoside (3 g/m2 x 4) (BEA regimen) was used for pretransplant conditioning in 13 patients. For the remaining 47 patients, granulocyte colony-stimulating factor (G-CSF) was administered concurrently with the BEA regimen during conditioning. Unpurged, cryopreserved PBSC containing a median number of 5.4 x 10(8) MNC/kg or 12 x 10(4) CFU-GM/kg were reinfused at transplantation. The median number of days to granulocytes exceeding 500/microl and last platelet transfusion were 15 (8-44) and 24 (0->180), respectively. The 3-year probabilities of disease-free survival (DFS) and relapse were 78.6 and 21.4% for patients transplanted in first remission, 29.6 and 64.4% for those in second or third remission, and 11.1 and 77.8% for those in relapse, respectively. There were no transplant-related deaths within 100 days of transplantation. Age, disease status at transplantation, and number of induction chemotherapies to first complete remission were risk factors affecting the outcome of ABSCT. These results of ABSCT for AML in first remission warrant a prospective study of ABSCT as post-remission therapy.

Acute Disease↗

PubMed1997

Angina pectoris occurring during granulocyte colony-stimulating factor-combined preparatory regimen for autologous peripheral blood stem cell transplantation in a patient with acute myelogenous leukaemia.

We describe a patient with acute myelogenous leukaemia who developed angina pectoris during pretransplant conditioning for autologous peripheral blood stem cell transplantation (PBSCT); the conditioning regimen consisted of cytotoxic drugs in combination with granulocyte colony-stimulating factor (G-CSF). Neutrophilia and hypercoagulability were observed at the time of angina pectoris. Recurrence of angina pectoris was not seen after nitrate and aspirin therapy. Exercise stress testing performed after PBSCT suggested the presence of myocardial ischaemia. Therefore cases at risk of vascular events should be carefully managed with prophylactic treatment during G-CSF administration.

Angina Pectoris↗

PubMed1997

Analysis of T-cell receptor beta of the T-cell clones reactive to the human PDC-E2 163-176 peptide in the context of HLA-DR53 in patients with primary biliary cirrhosis.

T-cell-mediated autoimmune mechanisms are considered to be involved in the pathogenesis of primary biliary cirrhosis (PBC). In the previous study, we identified the immunodominant T-cell epitope on the E2 component of pyruvate dehydrogenase complex (PDC-E2) in patients with PBC who have HLA-DRB4*0101. In this report, we revealed that the frequency of the T cells reactive to the human PDC-E2 163-176 peptide is significantly increased in the peripheral blood of patients with PBC as compared with healthy subjects. We also confirmed that these T cells were all restricted with HLA-DRB4*01 (DR53) by using HLA-DR-transfected L cells. These results together with the evidence that the immunodominant B-cell epitope overlaps with the human T-cell epitope of the PDC-E2 antigen indicate that the T cells reactive to this epitope are closely associated with the pathogenesis of PBC at least in patients who have HLA-DR53. Therefore, we analyzed the T-cell receptor (TCR) Vbeta sequence of the five different T-cell clones and the three T-cell clones derived from three patients with PBC and healthy subjects, respectively, which are reactive to the human PDC-E2 163-176 peptide in the context of HLA-DR53. The Vbeta- and the Jbeta-gene usages were diverse among the T-cell clones (Vbeta11-Jbeta1.4, Vbeta8-Jbeta1.2, Vbeta12-Jbeta2.1, Vbeta10-Jbeta1.5, and Vbeta20-Jbeta2.1) in patients with PBC. By contrast, in the third complementarity determining region (CDR3), G was frequently found and GXG or GXS motif was identified in all T-cell clones. Moreover, RGXG motif was found in three clones generated from two patients. In healthy subjects, the Vbeta- and the Jbeta-gene usages were also diverse, and GXG and RGXG motif were found. These results indicate that the T cells may recognize the ligand (the human PDC-E2 163-176 peptide/HLA-DR53 complex) using the limited motif in the CDR3 region and that the design of CDR3-specific immunotherapy would be possible using these motifs.

Amino Acid Sequence↗

PubMed1997

The role of T cells in primary biliary cirrhosis.

While fervently studied by several laboratories, the role of T cells in the pathogenesis of primary biliary cirrhosis (PBC) still remains a mystery. The studies concerning cell phenotype, antigen specificity, and major histocompatibility complex (MHC)-T-cell receptor (TCR) interaction gathered thus far all address important aspects of this intriguing conundrum. However, the lack of an animal model and the genetic diversity of the human population with PBC make this task even more difficult. The possibilities regarding immune therapy resulting from such studies are of great importance. Future work concerning the T-cell epitopes--for both the pyruvate dehydrogenase complex (PDC), its related mitochondrial autoantigens, and any as yet unidentified PBC-specific autoantigens--may provide valuable information with regard to disease therapy. In addition, knowledge with regard to TCR usage and MHC association will help to clarify the pathogenic mechanisms of this enigmatic disease.

Antigen-Presenting Cells↗

PubMed1997

Direct evidence for the contribution of B cells to the progression of insulitis and the development of diabetes in non-obese diabetic mice.

The non-obese diabetic (NOD) mouse is an excellent animal model of autoimmune diabetes associated with insulitis. The progression of insulitis causes the destruction of pancreatic beta cells, resulting in the development of hyperglycemia. Although it has been well documented that T cells are required for the development of insulitis and diabetes in NOD mice, the importance of B cells remains unclear. To clarify the role of B cells in the pathogenesis of NOD mice, we therefore generated B cell-deficient NOD (B-NOD) mice. Surprisingly, none (of 13) of the B-NOD mice developed diabetes by 40 weeks of age, while the control littermates with B cells (B+NOD) suffered from a high proportion (43 of 49) of diabetes. The insulin reactivity of B+NOD mice was significantly impaired, while the B-NOD mice showed a good insulin response, thus suggesting the pancreatic beta cell function to be well preserved in B-NOD mice. Although B-NOD mice did develop insulitis, the extent of insulitis was significantly suppressed. These data thus provide the direct evidence that B cells are essential for the progression of insulitis and the development of diabetes in NOD mice.

Animals↗

PubMed1997

Pharmacological studies on Puerariae flos III: protective effects of kakkalide on ethanol-induced lethality and acute hepatic injury in mice.

Kakkalide, one of the major isoflavonoid components of Puerariae flos, has been investigated for its effect on ethanol-induced intoxication and on hepatic injury, including hyperglycaemia, in mice. Kakkalide reduced mortality associated with administration of ethanol. At doses of 100 and 200 mg kg-1 the effect of kakkalide was significant. The same dose of kakkalide prevented increased serum glutamic oxaloacetic transaminase and glutamic pyruvic transaminase activity. At a dose of 200 mg kg-1 it also counteracted ethanol-induced elevation of glucose levels. These results suggest that kakkalide might be useful for counteracting the effects of alcohol and might be effective for treating hepatic injury.

Acute Disease↗

PubMed1997

[Immunodeficiency and carcinogenesis in patients with chronic active Epstein-Barr virus infection].

Three adult patients with chronic active Epstein-Barr virus infection (CAEBV) had high anti-EBV-VCA antibody, positive anti-EA, low anti-EBNA and were associated with systemic lymphadenopathies and immunosuppression. The case 1 and 2 had elevated serum immunoglobulin levels, and recurrent infections, and case 3 showed pancytopenia. These 3 cases developed both EBV and latent membrane protein (LMP) positive malignant histiocytosis, EBV positive but LMP negative plasmacytoma, and EBV negative acute myelogeneous leukemia, respectively. It was suggested that CAEBV belonged to high risk groups for the development of malignant neoplasms. Since HLA of the case 1 and his father was identical, we conducted a in vitro cytotoxicity test using EBV transformed autologous B lymphocytes, K562 cells, and Raji cells to clarify the association of immunosuppression and HLA. The case 1 showed a low level of specific cytotoxicity to autologous EBV transformed B cells, while his parents were negative for the specific cytotoxicity. The patient and his parents developed inducible cytotoxicity to all targets after in vitro incubation of peripheral mononuclear cells with recombinant interleukin 2 (rIL-2) for 7 days. The patient and his mother showed lower enhancement of cytotoxicity, while HLA identical father could induce good cytotoxic activity to all targets as well as normal controls, indicating that a low IL-2 induced cytotoxic activity observed in CAEBV was independent of HLA associated immunoregulation at least in the case 1. Further studies are required to clarify the exact mechanisms responsible for the development of CAEBV.

Adult↗

PubMed1997

[Severe left ventricular dysfunction in a patient with primary Sjögren's syndrome].

A 43-year-old woman was admitted to our hospital for evaluation of shortness of breath and palpitation on exertion. She had a 20-year history of dry mouth and a 10-year history of recurrent pneumonia. She had been diagnosed as having primary Sjögren's syndrome with interstitial pneumonia at 42 years of age. On admission, cardiac ultrasonography revealed reduced left ventricular systolic function. Complications that would elicit cardiac manifestations such as viral myocarditis, amyloidosis, sarcoidosis, and ischemic heart disease, were excluded. Oral corticosteroid therapy was effective for alleviating symptoms. In this patient, it appears that primary Sjögren's syndrome is involved in the reduced left ventricular systolic function.

Adult↗

PubMed1997

Significance of quantitative analysis of AML1/ETO transcripts in peripheral blood stem cells from t(8;21) acute myelogenous leukemia.

Autologous peripheral blood stem cell transplantation (PBSCT) is replacing autologous bone marrow transplantation (BMT) in the treatment of leukemia. One of the potential advantages of autologous PBSCT is the possibility that peripheral blood stem cells (PBSC) are less likely to be contaminated by leukemic cells than bone marrow grafts. However, the major problem still remains the high incidence of leukemic relapse following autologous PBSCT, which may be caused by the reinfusion of PBSC contaminated by leukemic cells. Recently, we have developed a quantitative assay using competitive reverse transcriptase polymerase chain reaction that estimates the number of AML1/ETO transcripts in t(8;21) acute myelogenous leukemia (AML), in order to determine the degree of leukemic cell contamination in PBSC harvests, and to monitor minimal residual disease (MRD) quantitatively in patients with t(8;21) AML. Our data indicate that although PBSC harvests collected after consolidation chemotherapy are contaminated by leukemic cells, the degree of leukemic cell contamination decreases with repeated cycles of chemotherapy. Furthermore, the MRD in PBSC harvests is less than in the corresponding bone marrow obtained on the day of the PBSC collection. There appears to be no relationship between the number of AML1/ETO transcripts found in the infused PBSC harvests and the incidence of leukemic relapse following autologous PBSCT in our study. However, a substantial decrease of AML1/ETO transcripts was seen following autologous PBSCT. Thus, the quantitative analysis of AML1/ETO transcripts may be clinically useful in patients with t(8;21) AML.

Blood Cells↗

PubMed1997

[A case of colon cancer with local recurrence successfully treated by systemic and local intra-arterial chemotherapy using a combination of 5-fluorouracil, interferon-alpha 2A, leucovorin and carboplatin].

A 59-year-old man with colon cancer was diagnosed as having a local recurrence of the disease, forming a huge intra pelvic tumor, accompanied by pulmonary metastasis 16 months after hemicolectomy. He received alternate systemic and local chemotherapy consisting respectively of a 5-day course of continuous infusion of 5-FU 600 mg/m2/day, bolus injection of leucovorin (LV) 20 mg/m2/day, intramuscular injection of interferon (IFN)-alpha 2a 6 x 10(6) IU/day, and intra-arterial administration of 5-FU, LV and carboplatin using reservoir catheter through pudendal artery, each repeated every 3 weeks. After 6 systemic and 8 local treatments, metastatic lesions disappeared and the intra-pelvic tumor shrunk by 62%, indicating a partial response. The patient then underwent dissection of the intra-pelvic tumor. Pathological examination indicated a curative resection. Alternate systemic and local intra arterial chemotherapy using a combination of 5-FU, LV, IFN and and carboplatin is highly promising for metastatic colorectal cancer with local recurrence.

Adenocarcinoma↗

PubMed1997

[Foscarnet therapy for ganciclovir-refractory cytomegalovirus hepatitis in a patient who underwent bone marrow transplantation from an unrelated donor].

Cytomegalovirus (CMV) hepatitis refractory to ganciclovir treatment occurred after prolonged administration of ganciclovir in a 36-year-old woman with chronic myelogeneous leukemia who had undergone allogeneic bone marrow transplantation (BMT) from an HLA-identical unrelated donor. The number of CMV antigen-positive leukocytes in blood were well correlated with the serum levels of transaminases and the antigenemia assay was useful in monitoring CMV hepatitis. The patient was treated with foscarnet, a potent inhibitor of CMV DNA-polymerase, which led to rapid improvement of the CMV antigenemia and the transaminase concentrations. Foscarnet therapy should be considered for ganciclovir-resistant CMV disease in the setting of BMT.

Adult↗

PubMed1997

C5a induces tissue factor activity on endothelial cells.

Tissue factor (TF) is an integral membrane glycoprotein that serves as a cofactor for blood coagulation factor VIIa. The induction of TF on the surface of endothelial cells is initiated by various stimuli including lipopolysaccharide, interleukin-1 beta, and tumor necrosis factor alpha. We have demonstrated that recombinant human C5a induces TF activity in a dose-dependent fashion in human umbilical vein endothelial cells (HUVEC). Peak activity (4.9-fold increase) was obtained 3-6 h after treatment with 10 microM C5a. TF mRNA as assessed by RT-PCR method was also significantly increased (3.75-fold) after 3 h incubation with C5a, suggesting that C5a induces TF activity on HUVEC, at least in part, by enhancing the level of TF mRNA. The increase in TF activity by C5a was inhibited by methylprednisolone. The induction of TF on endothelial cells by C5a may represent one of many potential interrelationships between the inflammatory and coagulation schemes.

Blood Coagulation↗

PubMed1997

Molecular and genetic analysis of two patients with Bernard-Soulier syndrome--identification of new mutations in glycoprotein Ib alpha gene.

We investigated two unrelated patients with Bernard-Soulier syndrome (BSS) by performing molecular and genetic analysis. A flow cytometric and immunoblotting analysis showed GP Ib alpha to be absent from the platelet membrane of both patients. Other glycoproteins that formed GP Ib/IX/V complex were present on the platelets, but in decreased amounts. Therefore, GP Ib alpha gene from both cases was sequenced after PCR amplification and subcloning. We identified a homozygous mutation of a dinucleotide deletion within the TGTG repeat at cDNA number 972 to 975 in GP Ib alpha gene from Case 1. In Case 2, compound heterozygosity was demonstrated in GP Ib alpha gene; an insertion of a single base (T) at cDNA number 1,418 in one allele, and a deletion of a single base (A) within the 7-adenine repeat at cDNA number 1,438 to 1,444 in another allele. The three new mutations in both patients appeared to cause a frameshift, which created a new termination codon shortly thereafter, and thus lead to a GP Ib alpha deficiency on the platelet membrane. Truncated mutant proteins could be detected in the plasma and platelets of Case 2, but not of Case 1. According to these findings, it is thus supposed that the properties and conformation of additional COOH-terminal peptides, which were supposedly synthesized as results of the mutations, may have an important role on the processing of mutant GP Ib alpha in megakaryocytes and platelets.

Adult↗