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Biomedical subjects

Yoshiro Niitsu

Publications and source records attributed to Yoshiro Niitsu.

At least 109 records · Page 6Linked to original sources
PubMed2002

Granulocyte-colony stimulating factor enhances the expression of transforming growth factor-beta mRNA in CD4-positive peripheral blood lymphocytes in the donors for allogeneic peripheral blood stem cell transplantation.

The degree of acute graft-versus-host disease (GVHD) after allogeneic peripheral blood stem cell transplantation (allo-PBSCT) has been observed to be, unexpectedly, of an equal level to that after bone marrow transplantation. To explain this phenomenon, we hypothesized that granulocyte-colony stimulating factor (G-CSF) administration may induce transforming growth factor (TGF)-beta producing T cells in the donors. Five donors received 10 microg/kg G-CSF subcutaneously for 4 days. The TGFbeta mRNA expression in CD4(+) cells as measured by real time reverse transcription-polymerase chain reaction increased after G-CSF administration. This elevation is considered to be one additive mechanism of repression of acute GVHD after allo-PBSCT.

Blood Donors↗
PubMed2002

E1B-55K-deleted adenovirus expressing E1A-13S by AFP-enhancer/promoter is capable of highly specific replication in AFP-producing hepatocellular carcinoma and eradication of established tumor.

Here, we constructed a recombinant replication-competent adenovirus (rRCAd; AdAFPep/Rep) that expresses both E1A-13S driven by the alpha-fetoprotein (AFP) enhancer/promoter (AFPep) lacking any silencers in the 5'-flanking region of the AFP gene, and 55K-deleted E1B driven by the cytomegalovirus (CMV) promoter. We then examined the feasibility of gene therapy utilizing this virus for AFP-producing hepatocellular carcinoma (HCC). AdAFPep/Rep lysed all the AFP-producing HCC cell lines (HuH7, HepG2, PLC/PRF/5 (P5)) examined at a multiplicity of infection (MOI) as low as 0.1 and did not lyse primary human hepatocytes (Hc) at a MOI as high as 100, indicating that the rRCAd virus can lyse AFP-producing HCC cells with a higher specificity and potency than previously reported. Furthermore, this virus was capable of complete eradication of a preestablished HuH7-cell tumor by a single intratumoral injection of 10(8) plaque-forming units (pfu) of AdAFPep/Rep. Thus, AdAFPep/Rep may be applicable for clinical use.

Adenovirus E1A Proteins↗
PubMed2002

A pleural effusion caused by fibrous hematopoietic tumor successfully treated with prednisolone in a patient with agnogenic myeloid metaplasia with myelofibrosis.

A 46-year-old woman suffering from agnogenic myeloid metaplasia (AMM) since 1994 was being followed as an outpatient. In November 1999, she exhibited respiratory failure caused by massive pulmonary effusion, which was speculated to have been produced by chest tumors. A biopsy specimen revealed findings compatible with fibrous hematopoietic tumor (FHT): prominent fibroblasts and fibrosis with scantv megakaryocytes. Serum concentrations of transforming growth factor (TGF)-beta and platelet-derived growth factor (PDGF) were significantly higher than those of other cases of AMM without FHT. The effusion did not respond to administrations of various chemotherapeutic agents, but after prednisolone administration, the effusion disappeared and the tumors also diminished. TGF-beta and PDGF were the possible causes of FHT formation, and for such fibrotic extramedullary regions, the administration of prednisolone should be considered.

Anti-Inflammatory Agents↗
PubMed2002

Recent advance in molecular iron metabolism: translational disorders of ferritin.

Ferritin, composed of H-subunits and L-subunits, plays important roles in iron storage and in the control of intracellular iron distribution. Synthesis of both subunits is controlled by common cytoplasmic proteins, iron regulatory proteins (IRP-1 and IRP-2) that bind to the iron-responsive element (IRE) in the 5'-untranslated region of ferritin messenger RNA (mRNA). When intracellular iron is scarce, IRPs display IRE binding to suppress translation of mRNA. When cellular iron is abundant, IRPs become inactivated (IRP-1) or degraded (IRP-2). In the last few years, IRE mutations that cause disorders due to dysregulation of ferritin subunit synthesis have been identified. Hereditary hyperferritinemia-cataract syndrome is associated with point mutations or deletions in the IRE of L-subunit mRNA and is characterized by constitutively increased synthesis of L-subunits but is unrelated to iron overload. A single-point mutation in the IRE of H-subunit mRNA in members of a family affected with dominantly inherited iron overload has been reported. This review summarizes the current understanding of the translational disorders caused by IRE mutations in ferritin mRNA.

Cataract↗
PubMed2002

Mechanisms for increment of platelet associated IgG and platelet surface IgG and their implications in immune thrombocytopenia associated with chronic viral liver disease.

In addition to hypersplenism, immunological destruction of platelets by elevated platelet associated IgG (PAIgG) and platelet surface IgG (PSIgG) has been proposed as a causative factor for thrombocytopenia in chronic liver disease (CLD), although the implication of PAIgG may be debatable since recent investigations on idiopathic thrombocytopenic purpura disclosed the fact that PAIgG largely relates to the intra-platelet IgG in alpha-granules and not to PSIgG. Further, with regard to the elevated PSIgG of CLD, characterization as to whether it mainly represents anti-platelet glycoprotein (GP) antibodies or IgG contained in the immune complex has not been elucidated. Thirty-seven patients with chronic viral liver disease (CVLD); 31 hepatitis C and 6 hepatitis B were included in this study. First we monitored the changes in levels of PAIgG, alpha-granule IgG, PSIgG and mean platelet volume (MPV) during the course of partial splenic arterial embolization (PSE). The elevated level of PAIgG decreased after PSE, paralleling that of alpha-granule IgG, while PSIgG showed no change; MPV decreased reciprocally with the increase of platelet count. These results indicate that the increment of PAIgG in CVLD may be caused by accelerated destruction of platelets; this generally evokes hyperproduction of large-sized thrombocytes, which have an increased capability to uptake circulating IgG. To characterize PSIgG, we then tested CVLD patients for antiplatelet GP antibodies and found only a 5.4% positivity. It was also found that circulating immune complex levels in CVLD patients were clearly elevated, correlating with the levels of PSIgG. Thus, it was surmised that immune complexes bound to the platelet surface, and not platelet specific GP antibodies, may be playing a crucial role in platelet destruction of CVLD, possibly through phagocytosis by macrophages.

Journal Article↗
PubMed2002

Effect of Helicobacter pylori eradication on platelet recovery in Japanese patients with chronic idiopathic thrombocytopenic purpura and secondary autoimmune thrombocytopenic purpura.

The prevalence of Helicobacter pylori infection and the effect of its eradication on platelet count in 48 Japanese patients with autoimmune thrombocytopenic purpura (AITP), including 40 chronic idiopathic thrombocytopenic purpura (ITP) and eight secondary AITP, were investigated. H. pylori infection was found in 25 ITP patients (62.5%) and in two secondary AITP (25%). H.pylori eradication was obtained in 19 of 19 infected ITP patients (100%), who were not in remission (platelets < 100 x 109/l) at the time of infection assessment. During follow-up (median 14.8 months), 12 of 19 H. pylori-eradicated patients (63.2%) showed a significant increase in platelet count accompanied by a significant decrease of platelet-associated immunoglobulin G (IgG). This response was maintained in all responding patients throughout the follow-up period. However, two infected patients with secondary AITP did not show platelet increase after eradication. The assessment of H. pylori infection and its eradication should be attempted in ITP as this approach could be an effective strategy, at least for some of these patients.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2002

A patient with paroxysmal nocturnal haemoglobinuria in whom granulocyte colony-stimulating factor administration resulted in improvement of recurrent enterocolitis and its associated haemolytic attacks.

We report an elderly patient with paroxysmal nocturnal haemoglobinuria (PNH), having recurrent enterocolitis and haemolytic attacks associated with cellular immunodeficiency. On admission, the patient had normal neutrophil count and function but a decreased T-cell count, decreased mitogenic reactions, and a negative tuberculin test. Granulocyte colony-stimulating factor (G-CSF) was administered, resulting in an increased T-cell count, normalization of T-cell function, increased blood levels of helper T cell (Th)1 and Th2 cytokines and improvement in the enterocolitis and haemolytic attacks. This suggests that G-CSF may be useful in the treatment of elderly PNH patients with cellular immunodeficiency.

Aged↗
PubMed2002

Role of endotoxin in NF-kappaB activation by ethanol in rat hepatocytes.

BACKGROUND: Endotoxin plays an important role in the progression of alcoholic liver injury. However, the role of endotoxin in acute activation of NF-kappaB by ethanol remains unclear. METHODS: In primary rat hepatocyte cultures treated with ethanol and/or endotoxin, the DNA-binding activity of NF-kappaB in the nuclear extract was estimated by electrophoretic mobility shift assay. After pretreatment of a CYP2E1 inhibitor, 4-methyl pyrazole or diallyl sulfide, NF-kappaB activity was also measured in the same manner. RESULTS: Ethanol or endotoxin caused activation of NF-kappaB in primary rat hepatocytes. Taking 50 mM of ethanol and endotoxin together raised the rapid increase in NF-kappaB activation, but both 100 mM of ethanol and endotoxin treatment reduced the increase. Addition of diallyl sulfide decreased the activity at rapid phase but increased it after 60 min, whereas addition of 4-methyl pyrazole caused no change of the activity at rapid phase but raised it after 60 min. Pretreatment with both endotoxin and a CYP2E1 inhibitor raised the activation of NF-kappaB constantly after ethanol addition. These findings suggest that endotoxin plays a critical role in the metabolism-independent activation of NF-kappaB by ethanol. CONCLUSIONS: Endotoxin raised metabolism-independent activation of NF-kappaB by high ethanol in rat hepatocytes.

Animals↗
PubMed2002

Enhanced expression of type IV collagen-binding protein (p29) in Fyn-transfected murine fibrosarcoma cells.

We investigated the mechanism of the enhancement of metastatic potential induced by transfection of the fyn gene, a member of the src family. We employed two murine fyn cDNA-transfected clones, ML-SN1 and ML-SN2, which were previously established from an ML-01 low-metastatic clone of Meth A sarcoma of BALB / c mice and were proven to have higher metastatic ability than ML-01 and the mock-transfected clone ML-MT-neo (Takayama et al., 1993). Our present investigation revealed that the two transfectants showed higher metastatic ability and higher rates of adherence to type IV collagen than ML-MT-neo. However, no difference was found in in vitro or in vivo growth rates, attachment to laminin or endothelial cells or cell motility through a reconstituted basement membrane. Analysis of surface membrane proteins labeled with (125)I on SDS-PAGE showed that a 29 kD band specifically bound to type IV collagen-coupled beads was more intense in ML-SN2 than in ML-MT-neo. Genistein, a protein tyrosine kinase inhibitor, dramatically reduced protein tyrosine kinase (PTK) activity of ML-SN2 in a dose-dependent fashion, corresponding to the reduction of adhesiveness to type IV collagen. The expression of the type IV collagen-binding protein (p29) of ML-SN2 was also reduced significantly by genistein treatment. These results suggested that the fyn product in Meth A cells augments the expression of a type IV collagen-binding protein through elevation of the PTK activity of the membrane fraction and thus facilitates the metastasis of Meth A.

Animals↗
PubMed2002

[Mixed warm and cold antibody-type autoimmune hemolytic anemia in a healthy pregnant woman with primary cytomegalovirus infection].

A 25-year-old previously healthy pregnant woman was admitted to our hospital because of severe anemia (Hb 6.7 g/dl), and diagnosed as having mixed-type autoimmune hemolytic anemia (AIHA) due to de novo cytomegalovirus (CMV) infection. After daily administration of prednisolone, the anemia gradually resolved and the patient delivered a healthy baby. This is the first report of a healthy person suffering from mixed-type AIHA due to de novo CMV infection.

Anemia, Hemolytic, Autoimmune↗
PubMed2002

[A new regional arterial infusion chemotherapy for patients with advanced pancreatic cancer].

Various arterial infusion chemotherapies have been tried for the purpose of local control of advanced pancreatic carcinoma. However, these treatments were not effective against the primary lesion because of its special anatomical position and the complex hemodynamics, although they were effective against the liver metastases. Therefore, the vascular supply distribution was altered by superselective embolization to control the primary legion in the pancreas, after transcatheter peripancreatic arterial embolization toward the primary site. Furthermore, bilateral (hepatic and splenic) arterial infusion chemotherapy was applied to both the primary site and liver metastasis. As a result, the response rate was 73.9%, with a mean survival period 18.26 +/- 10.06 months. We believe that the current chemotherapy was an effective treatment for unresectable pancreatic cancer since it was possible to treat patients with little harm to their quality of life.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

[Adult-onset Still's disease accompanied by hemophagocytic syndrome at onset].

A 43-year-old woman was admitted for examination of fever, an elevated transaminase level, LDH, skin eruption, sore throat and bicytopenia. As bone marrow examination revealed an increased proportion of histiocytes and active phagocytosis, hemophagocytic syndrome (HPS) was diagnosed. After admission, the peripheral blood counts recovered spontaneously and the HPS subsided, but other symptoms persisted and the neutrophil count increased. At this time, we diagnosed the patient as having adult Still's disease. All the symptoms disappeared after administration of prednisolone. The markedly increased concentrations of TNF-alpha and IFN-gamma in the peripheral blood at the time of HPS declined gradually, and the IL-6 concentration increased at the time of diagnosis of Still's disease. However, all of these concentrations normalized after administration of prednisolone. As HPS and Still's disease have a common etiology, and each shows high concentrations of IFN-gamma, IL 6 and TNF-alpha, the symptoms are similar in both diseases. In particular, a relationship between HPS and high concentrations of TNF-alpha and IFN-gamma is suspected.

Adult↗
PubMed2002

[A case of large-cell lung cancer with liver metastasis successfully treated using combination chemotherapy with CDDP and vinorelbine].

A 38-year-old woman presented to our hospital with the chief complaint of dyspnea. A chest radiograph showed pleural effusion of the right lung and a CT scan revealed liver metastasis. A tumor biopsy done under bronchoscopy revealed large-cell carcinoma of the lungs. She was given 4 courses of a combination therapy consisting of CDDP (80 mg/m2) and vinorelbine (25 mg/m2). The primary tumor in the right lung and liver metastasis were markedly reduced in size and a partial response was obtained. The combination therapy of CDDP and vinorelbine may become a standard chemotherapy for advanced non-small cell lung cancer.

Adult↗
PubMed2002

[Treatment of chronic myelogenous leukemia with imatinib mesylate resulting in hematological remission and marked regression of myelofibrosis].

We treated two chronic phase chronic myelogenous leukemia patients with imatinib mesylate. Hematological complete remission and significant regression of bone marrow fibrosis were observed in both patients. The large amount of TGF-beta produced by increased bone marrow megakaryocytes might have caused the myelofibrosis, and it was revealed that imatinib mesylate brought about regression of the myelofibrosis by reducing the number of megakaryocytes in both patients.

Aged↗
PubMed2002

[Usefulness of CT arteriography for transcatheter peripancreatic arterial embolization to patients with advanced pancreatic cancer].

We reported previously the clinical benefit of hepatic and splenic arterial infusion chemotherapy (HSAIC) for patients with advanced pancreatic cancer alter transcatheter peripancreatic arterial embolization (TPPAE). TPPAE has two therapeutic purposes: (1) preparation for effective arterial infusion chemotherapy, and (2) transcatheter arterial embolization (TAE) against pancreas head cancer. The present paper describes the advantage of CT arteriography in performing TPPAE for advanced pancreatic cancer. CTA was useful in identifying the arterial blood supply in pancreatic cancer, especially blood vessels branched off from the supramesenteric artery (SMA). Since the anti-tumor effect of TPPAE against pancreas head cancer is dependent mainly on whether the blood supply from SMA could be shut off, it is suggested that CTA is useful to evaluate the embolization effect of TPPAE.

Angiography↗
PubMed2002

[Successful treatment with G-CSF and corticosteroid of adult idiopathic autoimmune neutropenia presenting as recurrent enterocolitis].

A 63-year-old woman had previously been admitted to another hospital due to fever, abdominal pain and diarrhea. She was treated with fasting, antibiotics and G-CSF administration because of the coexistence of neutropenia, and the symptoms improved. However, discontinuation of G-CSF administration resulted in a recurrence of the neutropenia accompanied with enterocolitis. After admission to our hospital, a diagnosis for idiopathic AIN was performed as she tested positive in both granulocyte immunofluorescence and granulocyte agglutination tests. Administration of corticosteroid following G-CSF resulted in a continuous increase in the neutrophil count and the disappearance of anti-neutrophil autoantibodies.

Anti-Inflammatory Agents↗