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Biomedical subjects

Y Niho

Publications and source records attributed to Y Niho.

At least 55 records · Page 3Linked to original sources
PubMed2000

Suppression of insulitis and diabetes in B cell-deficient mice treated with streptozocin: B cells are essential for the TCR clonotype spreading of islet-infiltrating T cells.

In order to clarify the role of B cells in the development of insulitis and diabetes, B cell-deficient (B(-)) mice treated with streptozocin (STZ) were studied. The extent of insulitis and the cumulative incidence of diabetes were significantly suppressed in B(-) mice (P < 0.0001), indicating that B cells are crucial for the progression of insulitis and diabetes. Accumulation of both CD4(+) T cells and B cells was observed in islets of B(+) mice, while CD4(+) T cells but not B cells were found in B(-) mice. A few CD8(+) T cells and macrophages were detectable in both types of mice. The immunohistochemical study did not reveal any change in the subpopulations of infiltrating lymphocytes except for the absence of B cells in the B(-) mice. TCR V(beta) gene repertoire usage of islet-infiltrating T cells was restricted to some extent in the B(+) or B(-) mice, but there was no significant difference between the B(+) and B(-) mice, suggesting that the initial islet-reactive T cell response can occur in the absence of B cells. In contrast, TCR clonotype spreading of islet-infiltrating T cells was significantly suppressed in B(-) mice compared with B(+) mice (P < 0.0001). These data suggest that initial priming of T cells is not impaired and TCR V(beta) repertoire usage is not limited by the lack of B cells, while B cells are important essentially for the spreading of islet-infiltrating clonal T cells in autoimmune diabetic mice induced with STZ.

Animals↗
PubMed2000

Severe thrombocytopenia caused by digitoxin intoxication in a patient with heart failure associated with Sjögren's syndrome.

Congestive heart failure (CHF) related to Sjögren's syndrome is extremely rare. This report concerns a patient who presented with CHF and severe thrombocytopenia (5,000/microl). Serum concentrations of K, Mg and digitoxin were 3.2mmol/L, 1.4mg/L and 57.2ng/ml, respectively. Digitoxin intoxication was evident, seemingly evoked by hypokalemia, hypomagnesemia, hepatorenal dysfunction and hypothyroidism. The severe thrombocytopenia was considered to have been caused by this intoxication, as it disappeared soon after the digitoxin was discontinued and potassium was supplemented.

Cardiotonic Agents↗
PubMed2000

Influence of right atrial structure on outcome of radio-frequency catheter ablation for common atrial flutter.

Radiofrequency catheter ablation (RFCA) targeting the cavotricuspid isthmus is usually an effective treatment for common atrial flutter (AFL), except in a small subset of patients and the reason for this has yet to be elucidated. The present study investigated the relationship between the outcome of RFCA for common AFL and the anatomy of the right atrium as seen on angiography. Twenty consecutive patients who underwent RFCA for common AFL were divided into 2 groups according to the results of RFCA. Group A comprised 13 patients whose AFL was abolished, fulfilling the criteria of success by the conventional catheter approach, and group B comprised 7 patients whose AFL could not be abolished according to the criteria for success (n=4) or was abolished following an additional superior vena cava approach (n=3). On angiography, the cavotricuspid isthmus was longer (3.5+/-0.5 vs 2.2+/-0.6 cm) and deeper (0.94+/-0.35 vs 0.49+/-0.19 cm) in group B than in group A (both p<0.01). The height of the eustachian valve was also greater in group B than in group A (1.4+/-1.1 vs 0.48+/-0.48 cm, p<0.02). These results suggest that the anatomical structure of the cavotricuspid isthmus affects the outcome of RFCA for common AFL.

Adolescent↗
PubMed2000

Effect of thrombopoietin on acute myelogenous leukemia blasts.

It has been shown that the expression of c-mp1, which is a specific receptor for thrombopoietin (TPO), is restricted to the surface of megakaryocytes, platelets, human CD34+ progenitor cells and human erythroid/megakaryocytic leukemic cell lines. Recently, however, it has been reported that some acute myelogenous leukemia (AML) blasts expressed c-mp1 on their cell surface and proliferated in response to TPO. We therefore investigated the effect of thrombopoietin on the growth of leukemic blasts from patients with CD7-positive acute myelogenous leukemia (AML), which is a distinct biological and clinical subtype of AML. Significant growth responses of leukemic blasts to TPO were seen in 10/10 CD7+ and 7/20 CD7- AML cases using 3H-thymidine incorporation, while synergistic stimulatory effects of TPO with stem cell factor (SCF), interleukin-3 (IL-3), granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor were observed in both groups. In a leukemic blast colony assay, significant growth response to TPO was observed in 5/6 CD7+ and 4/17 CD7- AML cases examined. Furthermore, the expression of c-mp1 seemed to be higher in CD7+ AML cases than in CD7- cases, suggesting a relationship between the expression of c-mp1 and the proliferative response to TPO. These findings imply that CD7+ leukemic blasts express functional TPO receptors and proliferate in response to TPO. Thus CD7 expression on AML blasts may indicate the involvement of leukemic progenitors at an early stage of multipotent hemopoietic stem cells. In this review, we discuss the effect of TPO on AML blasts, especially in CD7+ AML cases.

Animals↗
PubMed2000

Vaccination of a refractory essential monoclonal cryoglobulinemia patient with cryoglobulin-pulsed dendritic cells.

We vaccinated a refractory essential monoclonal cryoglobulinemia patient with monocyte-derived DCs (Mo-DCs) pulsed with purified cryoglobulin as a tumor antigen. During the vaccinations, his acrocyanosis improved and we were able to reduce the number of hot baths used to treat his symptoms, with no side effects. Furthermore, cryoglobulin-specific proliferative responses were observed after the vaccination. As there was a recurrence of acrocyanosis after the final vaccination, vaccination with Mo-DCs pulsed with purified cryoglobulin would seem to be a useful treatment for refractory essential monoclonal cryoglobulinemia.

Antigens↗
PubMed2000

Antibody-free virion titer greatly differs between hepatitis C virus genotypes.

Hepatitis C virus (HCV) virions have been shown to be bound to antibodies in patients with chronic HCV infection. The sera from patients infected with genotype 1b HCV contained more antibody-free virions than those from patients with genotype 2a/2b HCV. When compared at the same levels of serum HCV RNA, free virion titers of genotype 2a/2b-infected patients were much lower than those of genotype 1b-infected patients, indicating that a larger fraction of HCV virions are bound to antibodies in the former than in the latter. The gene segments encoding the hypervariable region (HVR) 1, a principal neutralization epitope, of HCV were amplified from the patients' sera by reverse transcription-polymerase chain reaction. The majority of genotype 2a/2b-infected patients had very similar HVR 1 sequences to one another, whereas patients infected with genotype 1b HCV had highly heterogeneous sequences. Differences in the amount of antibody-free virion and HVR1 sequence variability between genotypes may have an implication in HCV pathogenesis.

Adult↗
PubMed2000

MLL gene rearrangement in t(9;11) acute myelogenous leukemia with minimal myeloid differentiation (FAB subtype M0).

A 25-year-old man was diagnosed with acute myelogenous leukemia (AML), French-American-British (FAB) subtype M0, based on cytochemical and flow cytometric findings. Cytogenetic analysis revealed the chromosome translocations t(9;11)(p22;q23), and MLL gene rearrangement was identified by Southern blotting. In adult AML, MLL gene rearrangement was initially reported in FAB M4 and M5 cases, and recently in M1 and M2 cases, but was rare in M0 or M3 cases. Because the sensitivity of detecting MLL gene rearrangement by cytogenetic analysis is extremely low compared with Southern blotting analysis, the MLL gene may be involved in substantial numbers of adult AML cases, regardless of FAB subtype.

Adult↗
PubMed2000

Down-regulation of human telomeric protein TRF1 gene expression during myeloid differentiation in human hematopoietic cells.

The maintenance of telomere length is crucial for cell survival. Recently, it has been indicated that the human telomeric protein TRF1 is involved in the negative feedback mechanism that stabilizes telomere length. We studied TRF1 mRNA expression in hematopoietic cells to clarify the relation between TRF1 and telomerase by semiquantitative reverse transcriptase-polymerase chain reaction. In polymorphonuclear cells and monocytes isolated from peripheral blood, relatively low levels of TRF1 mRNA expression were seen, compared with those of lymphocytes and CD34+. We then assessed TRF1 mRNA expression in CD34+ cells cultured in vitro with growth factors. After 4 weeks of culture, all the cells showed myeloid differentiation, and telomerase activity was down-regulated. TRF1 mRNA was expressed in CD34+ cells but was down-regulated in cells cultured for 4 weeks. We conclude that TRF1 mRNA expression is down-regulated in accordance with telomerase down-regulation during the course of myeloid differentiation.

Antigens, CD34↗
PubMed2000

[A case of metastatic colon carcinoma in which a continuous intrahepatic artery-infusion of 5-FU leucovorin and cisplatin, and systemic chemotherapy with CPT-11 was very effective].

We report a patient with metastatic colon carcinoma who was treated effectively with a continuous intrahepatic artery-infusion of 5-FU, Leucovorin and cisplatin, and systemic chemotherapy with CPT-11. A 50-year-old man was diagnosed as having well differentiated adenocarcinoma of the sigmoid colon with multiple liver metastases in March, 1997. Left hemicolectomy and subsequent catheterization into the common hepatic artery via the gastroduodenal artery were performed in April, 1997. He was treated with 3 courses of continuous intrahepatic artery-infusion of 5-FU, Leucovorin and cisplatin, and two courses of systemic chemotherapy with CPT-11 during hospitalization, followed by 6 courses of a similar intraarterial therapy in an outpatient setting. Reinstallation of the catheter into the hepatic artery via the femoral artery was performed because of occlusion of the reservoir. During the 6th course of intraarterial therapy, diarrhea, nausea, and vomiting appeared and angiography revealed a narrowing of the hepatic artery. Therefore, the intrahepatic artery-infusion therapy was reinitiated with doses of 5-FU, Leucovorin and cisplatin reduced to approximately 80%. After 5 courses of this therapy, the computed tomography scan showed a marked decrease in the size of the metastatic hepatic lesions by 90%, and the serum level of CEA decreased from 657.7 ng/ml to 4.5 ng/ml. No severe side effects were seen during the treatment. Though multiple lung metastases were indicated during the intrahepatic artery-infusion therapy, both the liver and lung metastases have been well controlled with continuous intrahepatic artery-infusion chemotherapy and systemic chemotherapy. The continuous intrahepatic arterial infusion of 5-FU, leucovorin and cisplatin appears to be very effective for the treatment of colon carcinoma with liver metastasis without reducing the quality of life.

Adenocarcinoma↗
PubMed2000

[Tacrolimus administration to a patient with cyclosporine-induced encephalopathy after allogeneic bone marrow transplantation].

A 25-year-old woman with severe aplastic anemia received allogeneic bone marrow transplantation from an HLA-identical sibling. Pretransplant conditioning comprised 3.6 Gy of total body irradiation and 200 mg/kg cyclophosphamide. Cyclosporine (CSP) and methotrexate were administered to prevent graft-versus-host disease (GVHD). The patient complained of severe headache soon after CSP administration on day-1. On day 3, convulsion developed and she lost consciousness for 15 min. CT and MRI demonstrated low density areas and high signals, respectively, in the frontal and parietooccipital lobes and splenium of the corpus callosum, suggesting brain edema probably induced by CSP. After immediate withdrawal of CSP, glycerol and prednisolone were instituted, and the patient's condition improved. Thereafter, she developed grade II acute GVHD. This was treated with tacrolimus, which produced no adverse effects including central nervous system (CNS) toxicity. This case illustrates that careful management of CNS disorders induced by CSP can be important in patients undergoing allogeneic bone marrow transplantation.

Adult↗
PubMed1999

Production of soluble granulocyte colony-stimulating factor receptors from myelomonocytic cells.

It has been speculated that a soluble form of G-CSFR might be physiologically present in humans, since G-CSFR mRNA that lacks a transmembrane domain has been identified from a human myelomonocytic cell line. Here, we demonstrate human soluble G-CSFR (sG-CSFR) of two different molecular sizes (80 and 85 kDa) on an immunoblot analysis using Abs generated against the amino-terminal, extracellular domain of the full-length G-CSFR. Both isoforms of sG-CSFR were able to bind recombinant human G-CSF (rhG-CSF). RT-PCR analysis with primers targeted outside of the transmenbrane region revealed that membrane-anchored G-CSFR is expressed at all maturation stages of purified myeloid cells, including CD34+CD13+ cells (blasts), CD11b-CD15+ cells (promyelocytes or myelocytes), CD11b+CD15+ cells (metamyelocytes and mature neutrophils), and CD14+ cells (monocytes). On the other hand, sG-CSFR mRNA was detectable in CD11b-CD15+, CD11b+CD15+, and CD14+ cells, but not in the CD34+CD13+ blast population. The serum concentration of both isoforms of sG-CSFR appeared to be correlated with the numbers of neutrophils/monocytes before and after rhG-CSF treatment in normal individuals. Thus, two isoforms of sG-CSFR are physiologically secreted from relatively mature myeloid cells and might play an important role in myelopoiesis through their binding to serum G-CSF.

Amino Acid Sequence↗
PubMed1999

Nonpathogenic common variants of IFNGR1 and IFNGR2 in association with total serum IgE levels.

Atopy is an immune disorder in which a Th2 dominant mechanism leads to high IgE levels and the clinical disorder asthma. It has been postulated that the Th1 cytokine IFNgamma, acting through its heterodimeric receptors, IFNgammaR1 and IFNgammaR2, in the induction/proliferation of Th1 cells, might suppress the Th2 responses that may underlie atopic asthma. However, neither murine nor human variants of IFNgamma associate with atopy. Several dysfunctional mutations have been identified in IFNgamma receptor genes (IFNGR1 and IFNGR2) in relation to severe and selective infections with poorly pathogenic organisms. However, little is known about common polymorphisms and their functional role in atopy. To test whether such variants of IFNGR1 and IFNGR2 relate to atopic asthma, we conducted a genetic association study in both British (n = 300) and Japanese (n = 200) populations. An intronic variant of IFNGR1 showed marginal association with total serum IgE levels in the British population compared with those with total IgE levels <30 IU/ml and those with >120-500 IU/ml [odds ratio = 2.00 (95% CI 1. 00-4.07), P = 0.048]. A coding variant, Gln64Arg of the IFNGR2, also associated with total serum IgE levels in the British population [chi(2) = 5.08, P = 0.024]. Further genetic and functional analyses are needed to clarify the role of variants of IFNgamma receptor genes in atopic immune disorder among different ethnic groups.

Asthma↗
PubMed1999

Progressive impairment of kidneys and reproductive organs in mice lacking Rho GDIalpha.

The Rho small G protein family members regulate various actin cytoskeleton-dependent cell functions. The Rho GDI (GDP dissociation inhibitor) family, consisting of Rho GDIalpha, -beta, and -gamma, is a regulator that keeps the Rho family members in the cytosol as the GDP-bound inactive form and translocates the GDP-bound form from the membranes to the cytosol after the GTP-bound form accomplishes their functions. Rho GDIalpha is ubiquitously expressed in mouse tissues and shows GDI activity on all the Rho family members in vitro. We have generated mice lacking Rho GDIalpha by homologous recombination to clarify its in vivo function. Rho GDIalpha -/- mice showed several abnormal phenotypes. Firstly, Rho GDIalpha -/- mice were initially viable but developed massive proteinuria mimicking nephrotic syndrome, leading to death due to renal failure within a year. Histologically, degeneration of tubular epithelial cells and dilatation of distal and collecting tubules were readily detected in the kidneys. Secondly, Rho GDIalpha -/- male mice were infertile and showed impaired spermatogenesis with vacuolar degeneration of seminiferous tubules in their testes. Thirdly, Rho GDIalpha -/- embryos derived from Rho GDIalpha -/- female mice were defective in the postimplantation development. In addition, these morphological and functional abnormalities showed age-dependent progression. These results suggest that the signaling pathways of the Rho family members regulated by Rho GDIalpha play important roles in maintaining the structure and physiological function of at least kidneys and reproductive systems in adult mice.

Age Factors↗
PubMed1999

Decreases in Ikaros activity correlate with blast crisis in patients with chronic myelogenous leukemia.

Gene targeting studies in mice have shown that the lack of Ikaros activity leads to T-cell hyperproliferation and T-cell neoplasia, establishing the Ikaros gene as a tumor suppressor gene in mice. This prompted us to investigate whether mutations in Ikaros play a role in human hematological malignancies. Reverse transcription-PCR was used to determine the relative expression levels of Ikaros isoforms in a panel of human leukemia/lymphoma cell lines and human bone marrow samples from patients with hematological malignancies. Among the cell lines examined, only BV-173, which was derived from a chronic myelogenous leukemia (CML) patient in lymphoid blast crisis, overexpressed the dominant-negative isoform, Ik-6. In 9 of 17 samples of patients in blast crisis of CML, Ikaros activity had been reduced either by drastically reducing mRNA expression (4 of 17) or by overexpressing the dominant-negative isoform Ik-6 (5 of 17). Significantly, expression of Ikaros isoforms seemed normal in chronic phase CML patients and patients with other hematological malignancies. In some cases, overexpression of the dominant-negative Ik-6 protein was confirmed by Western blot analysis, and Southern blot analysis indicated that decreases in Ikaros activity correlated with a mutation in the Ikaros locus. In summary, these findings suggest that a reduction of Ikaros activity may be an important step in the development of blast crisis in CML and provide further evidence that mutations that alter Ikaros expression may contribute to human hematological malignancies.

Adult↗
PubMed1999

Establishment of an embryonic stem (ES) cell line derived from a non-obese diabetic (NOD) mouse: in vivo differentiation into lymphocytes and potential for germ line transmission.

A non-obese diabetic (NOD) mouse-derived embryonic stem (ES) cell line has been stably maintained in an undifferentiated state with a characteristic ES cell-like morphology, expressing the stem cell marker alkaline phosphatase, and displaying a normal diploid karyotype. After injecting the NOD-ES cells into blastocysts, chimeric mice were obtained. Small but significant numbers of lymphocytes expressed the NOD-derived MHC allele. When a chimeric mouse was mated with C57BL/6 mice, an agouti mouse was obtained, having the NOD-derived H-2 I-A(beta)g7 haplotype. Thus, an NOD-ES cell line which can differentiate into lymphocytes with potential for germ line transmission was successfully established.

Animals↗
PubMed1999

The combination of polymorphisms within interferon-gamma receptor 1 and receptor 2 associated with the risk of systemic lupus erythematosus.

Genetic factors seem to play a significant role in susceptibility to systemic lupus erythematosus (SLE). We previously described the amino acid polymorphism (Val14Met) within the IFN-gamma receptor 1 (IFN-gammaRI), and that the frequency of the Metl4 allele in SLE patients was significantly higher than that of the healthy control population [Tanaka et al. (1999) Immunogenetics 49, 266-271]. We also found an amino acid polymorphism (Gln64Arg) within IFN-gamma receptor 2 (IFN-gammaR2). Since the IFN-gamma receptor is a complex consisting of IFN-gammaR1 and IFN-gammaR2, we searched for the particular combination of two kinds of amino acid polymorphisms found within the IFN-gamma receptor which plays a prominent role in susceptibility to SLE. The greatest risk of the development of SLE was detected in the individuals who had the combination of IFNGR1 Met14/Val14 genotype and IFNGR2 Gln64/Gln64 genotype.

Adolescent↗